2026-04-08T14:42:19Z http://oaibg.phaidrabg.rs/oai2.php

oai:eteze.bg.ac.rs:6 2013-09-19T00:00:00Z 1

Učestalost i tipovi mutacija u genima BRCA u porodicama sa pozitivnom istorijom za karcinom dojke i/ili jajnika u Srbiji Frequency and types of mutations in BRCA genes in families with positive history of breast/ovarian cancer in Serbia Dobričić, Jelena D. geni BRCA, kontrola ćelijskog ciklusa, popravka oštećenja DNK, kancerogeneza, karcinom dojke, karcionom jajnika, nasledni karcinom dojke i/ili jajnika, genetičko testiranje BRCA genes, cell cycle control, DNA repair, carcinogenesis, breast Datum odbrane: 23.5.2012. Uvod: Proteinski produkti gena BRCA1 i BRCA2 uključeni su u važne ćelijske procese, kao što su kontrola ćelijskog ciklusa i popravka oštećenja DNK. Mutacije u jednom od ovih gena predstavljaju korak bliže gubitku kontrole nad genomskom stabilnošću i ćelijskom deobom, pa osobe koje naslede mutacije u ovim genima češće oboljevaju od karcinoma dojke i/ili jajnika. Geni BRCA su veliki, mutacije su raspoređene duž celih gena bez grupisanja, što dodatno otežava njihovu detekciju. Spektar mutacija u genima BRCA različit je u različitim etničkim grupama. U nekim populacijama sa visokom učestalošću zastupljene su mutacije koje su u drugim populacijama retke. U isto vreme, veliki deo mutacija u genima BRCA detektovane su samo jednom, pa se može reći da većina porodica pod rizikom ima svoju sopstvenu porodičnu mutaciju. Mutacija 5382insC u 20. egzonu gena BRCA1 karakteristična je za slovenske populacije i njena učestalost opada od istoka ka zapadu Evrope. Oko 6-7% svih karcinoma dojke i oko 10% svih karcinoma jajnika je nasledno, povezano sa mutacijama germinativnih ćelija u genima BRCA1 i BRCA2. Nosioci mutacija u genima BRCA nose 5 do 8 puta veći životni rizik za oboljevanje od karcinoma dojke i 10 do 20 puta veći životni rizik za karcinom jajnika. Cilj istraživanja je bio da se otkriju najučestalije mutacije u genima BRCA1/2 u našoj populaciji i utvrdi koje se od njih mogu smatrati osnivačkim mutacijama, kako bi se ubrzalo, pojednostavilo i pojeftinilo BRCA testiranje. Da bi se ovaj cilj ostvario, bilo je neophodno utvrditi tipove i učestalosti mutacija u genima BRCA1 i BRCA2 kod osoba sa pozitivnom porodičnom istorijom za karcinom dojke i/ili jajnika u Srbiji. Osim toga, u sistematskom uzorku karcinoma dojke bilo je potrebno utvrditi učestalost mutacije 5382insC u genu BRCA1 kao potencijalne osnivačke mutacije u našoj populaciji. U ispitivanoj grupi osoba koje su testirane na prisustvo mutacija u genima BRCA1/2 procenjivana je i efikasnost predviđanja BRCAPRO programa. Materijal i metode: Analizirano je 85 uzoraka periferne krvi osoba sa povećanim rizikom za karcinom dojke i/ili jajnika koje potiču iz 69 porodica. Takođe, analiziran je i sistematski uzorak karcinoma dojke koji se sastoji od 257 uzoraka krvi obolelih. Prisustvo mutacija u genima BRCA analizirano je automatskim sekvenciranjem, dok je prisustvo mutacije 5382insC u genu BRCA1 u sistematskom uzorku određivano PCR-om specifičnim za alel. Za statističku obradu podataka korišćeni su testovi neparametrijske statistike: χ2 test i Fišerov test. Rezultati: Učestalost oštećujućih mutacija u uzorku porodica sa naslednim karcinomom dojke i/ili jajnika iznosi 10,59% (9/85). Sve detektovane oštećujuće mutacije su po tipu frameshift mutacije. Detektovane su i 3 nove porodično-specifične mutacije (1 u genu BRCA1 i 2 u genu BRCA2). Učestalost mutacije 5382insC u genu BRCA1 u sistematskom uzorku karcinoma dojke je 0,39% (1/257). Podizanjem granice BRCAPRO verovatnoće na 40% moguće je uočiti razliku između benignih polimorfizama i oštećujućih mutacija. Nije bilo moguće subgrupisanje neklasifikovanih varijanti na osnovu vrednosti BRCAPRO verovatnoće. BRCAPRO verovatnoća, sem sa srodnicima prvog i drugog stepena srodstva, koreliše i sa brojem obolelih srodnika u široj porodici. U odnosu na anatomsku lokalizaciju, BRCAPRO verovatnoća koreliše sa brojem srodnika obolelih od karcinoma dojke, ali ne i od karcinoma jajnika. Zaključak: Učestalost mutacija u genima BRCA1/2 kod ispitanika pod rizikom za nastanak naslednog karcinoma dojke i/ili jajnika u Srbiji slična je učestalostima dobijenim u drugim populacijama. Osim već poznatih mutacija u genima BRCA1/2 pokazane su i nove porodično-specifične mutacije. Nisu detektovane mutacije koje bi se mogle okarakterisati kao osnivačke mutacije za našu populaciju. BRCAPRO program se pokazao kao koristan pri odabiru osoba za BRCA testiranje, ali pri odabiru kandidata za testiranje, usled nedostataka BRCAPRO programa, treba analizirati i rodoslov. Podizanje granice BRCAPRO verovatnoće prilikom odabira ispitanika za BRCA testiranje sa 10% na 40% moglo bi da poveća efikasnost BRCA testiranja. Background: Protein products of BRCA1 and BRCA2 genes are included in important cellular processes, such as cell cycle control and DNA repair. Mutations in one of these genes is a step thowards losing control over genomic stability and cell division, and individuals who inherit mutations in these genes develop breast and/or ovarian cancer more frequently. BRCA genes are large, mutations are scattered throughout whole genes without clustering, which makes mutation detection even more difficult. The spectrum of BRCA mutations is different for each ethnic group. Mutations that are highly frequent in some populations are rare in other populations. At the same time, large proportion of BRCA mutations have been detected only once, and it can be said that majority of families under risk have their own family mutation. Mutation 5382insC in BRCA1 exon 20 is characteristic for Slavic populations and its frequency decreases from east to west of Europe. About 6-7% of all breast cancer cases and about 10% of all ovarian cancer cases are hereditary, associated to germ line mutations in BRCA1 and BRCA2 genes. BRCA mutation carriers have 5 to 8 times higher lifetime risk for breast cancer and 10 to 20 times higher lifetime risk for ovarian cancer. Aim of this study was to identify the most frequent BRCA1/2 mutations in our population and to find out which of them may be regarded as founder mutations, in order to make BRCA testing faster, easier and less expensive. In order to achieve this goal, it was necessary to identify types and frequencies of BRCA1/2 mutations in individuals with positive family history of breast and/or ovarian cancer in Serbia. In addition, it was necessary to identify the frequency of BRCA1 mutation 5382insC in breast cancer consecutive sample, as possible founder mutation in our population. In analysed group of individuals tested for the presence of BRCA1/2 mutations the efficiency of BRCAPRO software prediction was assessed. Material and methods: Eighty five peripheral blood samples from high risk individuals for breast and/or ovarian cancer from 69 families was analyzed. In addition, consecutive sample that included 257 blood samples from breast cancer patients was analyzed. The presence of BRCA gene mutations was analyzed by automatic sequencing, while the presence of 5382insC mutation in BRCA1 gene was determined by alel-specific PCR. For statistic analyses, non-parametric tests were used: χ2 test and Fisher test. Results: The frequency of deleterious mutations in sample of families with hereditary breast and/or ovarian cancer is 10.59% (9/85). All detected deleterious mutations are frameshift mutations. Three novel family-specific mutations have been detected (one in BRCA1 and two in BRCA2 gene). The frequency of BRCA1 mutation 5382insC in breast cancer consecutive sample is 0.39% (1/257). By raising the treshold of BRCAPRO probability to 40% it is possible to observe the difference between benign polymorphisms and deleterious mutations. Subgrouping of unclassified variants according to the value of BRCAPRO probability was not possible. BRCAPRO probability, in addition to the first and second degree relatives, correlates also with the number of more distant relatives who developed cancer. In relation to anatomic localisation, BRCAPRO probability correlates with the number of relatives who developed breast cancer, but not with the number of those who developed ovarian cancer. Conclusion: The frequency of BRCA1/2 mutations in probands under rsk for hereditary breast and/or ovarian cancer in Serbia is similar to those determined in other populations. In addition to already known BRCA1/2 mutations, new family-specific mutations have been detected. Mutation that could be qualified as founder mutations for our population have not been detected. BRCAPRO software has been shown to be useful in selection of probands for BRCA testing, but in this selection, due to BRCAPRO limitations, the pedigree should be analysed too. Raising the treshold for BRCAPRO probability in proband selection for BRCA testing from 10% to 40% could raise the efficiency of BRCA testing. Univerzitet u Beogradu Biološki fakultet Stamenković-Radak, Marina Branković-Magić, Mirjana Radulović, Siniša 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=6 https://fedorabg.bg.ac.rs/fedora/get/o:2127/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024476594 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:7 2013-09-19T00:00:00Z 1

Korelacija prisustva bakteriocinskih gena i proizvodnje bakteriocina prirodnih izolata Lactobacillus casei/paracasei grupe Correlation between the presence of bacteriocin genes and bacteriocin production in natural isolates of Lactobacillus casei/paracasei group Tolinački, Maja S. Lactobacillus, bakteriocini, abcT i acc geni, plazmid Lactobacillus, bacteriocin, abcT and acc genes, plasmid Datum odbrane 4.6.2012. Veliki broj vrsta roda Lactobacillus zauzima ključno mesto u proizvodnji fermentisanih mlečnih i mesnih proizvoda, prisutni su i u fermentisanom povrću i proizvodima od žitarica. Laktobacili se takođe koriste i u medicini usled pozitivnih efekata koje pojedini sojevi imaju na zdravlje domaćina. Pojedini sojevi laktobacila imaju i probiotski potencijal zahvaljujući sposobnosti produkcije različitih antimikrobnih jedinjenja, egzopolisaharida (EPS), proteinaza i dr. Vrste roda Lactobacillus poseduju potencijal da inhibiraju rast konkurentskih mikroorganizama u ekološkim nišama koje naseljavaju, korišćenjem širokog spektra različitih odbrambenih mehanizama uključujući proizvodnju velikog broja metaboličkih nusproizvoda, kao i mnogih biološki aktivnih agenasa proteinske prirode kao što bakteriocini. Sojevi koji proizvode više od jednog bakteriocina sa uskim, ali različitim inhibitornim spektrom, imaju veće šanse za opstanak u okruženju koje dele sa blisko srodnim vrstama sa kojima su u kompeticiji za iste nutrijente. Veliki broj sojeva proizvođača bakteriocina objašnjava se činjenicom da su bakteriocinske genetičke determinante često locirane na mobilnim genetičkim elementima, kao što su konjugativni plazmidi ili transpozoni, što omogućava njihovu široku distribuciju putem horizontalnog transfera gena. Cilj ove doktorske teze bio je da se utvrdi antimikrobni potencijal 52 soja Lactobacillus casei/paracasei grupe, zatim da se utvrdi rasprostranjenost bakteriocinskih gena neophodnih za produkciju bakteriocina BacSJ i acidocina 8912, a potom i korelacija prisustva bakteriocinskih gena i proizvodnje bakteriocina kod analiziranih sojeva. Ovakav pristup omogućio je identifikaciju potencijalnih bakteriocinskih gena kao i novih bakteriocina nezavisno od toga da li je analizirani bakterijski soj identifikovan kao proizvođač bakteriocina... A large number of Lactobacillus species play an important role in the production of fermented dairy products and meat products, and they are also present in fermented vegetables and grain products. Lactobacilli are used in medicine due to the positive effects that some strains have on the health of the host. Some Lactobacillus strains have a probiotic potential due to their ability to produce various antimicrobial compounds, exopolysaccharides (EPS), proteinases and other. Species of the Lactobacillus genus have the potential to inhibit the growth of competing microorganisms in the ecological niches they inhabit, using a wide range of various defense mechanisms including the production of a large number of secondary metabolic products, as well as many biologically active proteinaceous agents, such as bacteriocins. Strains that produce more than one bacteriocin with a narrow but different inhibitory spectrum have a better chance to survive in an environment shared with closely related species with which they are in competition for the same nutrients. A presence of huge number of bacteriocin producing strains could be explained by the fact that the bacteriocin genes were often located on mobile genetic elements such as conjugative plasmids or transposons, allowing their wide distribution via horizontal gene transfer. The aim of this doctoral dissertation was to determine the antimicrobial potential of 52 strains of Lactobacillus casei/paracasei group, followed by a comparative screening of the bacterial genomes in order to determine the distribution of BacSJ and acidocin 8912 encoding genes, and also to determine the correlation of presence of bacteriocin genes and bacteriocin production in the analyzed strains. This approach enabled identification of potentially new bacteriocins and putative bacteriocin genes regardless of whether the analyzed bacterial strains produced bacteriocin... Univerzitet u Beogradu Biološki fakultet Topisirović, Ljubiša Fira, Đorđe Kojić, Milan 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=7 https://fedorabg.bg.ac.rs/fedora/get/o:2128/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41195791 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:8 2013-09-19T00:00:00Z 1

Modulacija funkcije humanih dendritskih ćelija kombinovanom primenom agonista endozomnih Toll-sličnih receptora, Dektin-1 receptora i proinflamatornih citokina Modulation of the function of human monocyte derived dentritic cells by combined use of the endosomal Toll-like receptors, Dectin-1receptor and proinflamatory cytokines Dragičević, Ana Ž. CD40, CD4+ T-ćelijski odgovor, Dektin-1 receptor, humane dendritske ćelije monocitnog porekla, imunoterapija tumora, IFN-γ, TNF-α, Toll-sličan receptor 3, Toll-sličan receptor 7 CD40, Dectin-1 receptor, human monocyte-derived dendritic cells, IFN-γ, TNF-α, T helper immune response, Toll-like receptor 3, Toll-like receptor 7, tumor immunotherapy Datum odbrane:22.5.2012 Dendritske ćelije (DĆ), najpotentnije antigen-prezentujuće ćelije (APĆ), integrišu signale koje primaju sa različitih receptora u jedinstveni odgovor. Ključni značaj u ostvarivanju funkcija DĆ imaju receptori za prepoznavanje konzervisanih struktura, tzv. molekularnih obrazaca patogena (engl. Pattern Recognition Receptor, PRR). Aktivacija pojedinačnih PRR, posebno Toll-sličnih receptora (engl. Toll-like receptor, TLR) ili lektinskih receptora C-tipa poput dektina-1, dovodi do sazrevanja DĆ, dok je za razvoj efikasnog imunskog odgovora neophodna kooperacija više receptora. Dektin-1 receptor je, pored TLR, jedini receptor urođenog imuniteta čija aktivacija samostalno indukuje signalnu kaskadu koja dovodi do sazrevanja MoDĆ sa sposobnošću indukcije Th1 i Th17 odgovora. Imajući navedno u vidu, sledeći cilj ovog istraživanja je bio da se ispita efekat kombinovane primene Poly (I:C) i kurdlana, agonista dektin-1 receptora, na funkcionalne i fenotipske karakteristike MoDĆ. Za modulaciju sazrevanja i funkcija DĆ, pored stimulacije PRR, značajnu ulogu imaju i citokini prirodnog imuniteta koji se produkuju prilikom infekcije. Najnovija istraživanja ukazuju na ulogu TNF-α, jednog od najznačajnijih proinflamatornih citokina, u sazrevanju DĆ u ranim fazama infekcije kao i razvoju antigen-specifičnog odgovora. Naredni cilj našeg istraživanja bio je ispitivanje dozno- i vremenski- zavisnog efekta kombinovane primene TNF-α i Poly (I:C) na funkcionalne i fenotipske karakteristike MoDĆ. Poslednji deo istraživanja se odnosio na ispitivanje uticaja signala stečenog imuniteta koje DĆ dobijaju tokom interakcije sa T-limfocitima, uključujući signalizaciju preko CD40 receptora i receptora za IFN-γ na njihove karakteristike. Metode. Nezrele MoDĆ, dobijene kultivacijom humanih monocita, su stimulisane samim Poly (I:C) ili njegovom kombinacijom sa loksoribinom, kurdlanom ili TNF-α tokom 48h. Da bi ispitali uticaj signala stečenog imuniteta, MoDĆ stimulisane samim Poly (I:C) ili u kombinaciji sa TNF-α dalje su kultivisane u prisustvu ćelija J558 transfektovanim ligandom za CD40, solubilnog CD40L ili IFN-γ. U cilju ispitivanja uticaja kinetike aktivacije na kapacitet MoDĆ da polarizuju imunski odgovor, MoDĆ su stimulisane kombinacijama različitih koncentracija Poly (I:C) i TNF-α tokom 24h i 48h. Protočnom citofluorimetrijom su analizirane fenotipske karakteristike MoDĆ. Alostimulatorna sposobnost MoDĆ je određena testom mešane leukocitne reakcije. Produkcija citokina je određena ELISA metodom i testom za detekciju citokina pomoću imunofluorescentnih kuglica. Rezultati. Stimulacija MoDĆ optimalnom koncentracijom Poly (I:C) dovela je do povećanja ekspresije HLA-DR, CD86, CD40, CD54, CD83 i CCR7 molekula, povećanja produkcije IL-12, umerene produkcije IL-23 i niske produkcije IL-10. Ovako stimulisane MoDĆ dovode do povećane produkcije IFN-γ i umerene produkcije IL-17 tokom kokultivacije sa CD4+ T limfocitima. U preliminarnim eksperimentima nezrele MoDĆ su stimulisane različitim koncentracijama Poly (I:C) (5 μg/ml, 10 μg/ml, 25 μg/ml i 50 μg/ml), loksoribina (34 μg/ml i 85 μg/ml) i kurdlana (10 μg/ml , 50 μg/ml, 100 μg/ml i 200 μg/ml). Na osnovu fenotipskih i funkcionalnih karakteristika MoDĆ procenjeno je da je optimalna koncentracija za aktivaciju MoDĆ za Poly (I:C) 25 μg/ml, za loksoribin 85 μg/ml i za kurdlan 100 μg/ml, dok je koncentracija Poly (I:C) od 10 μg/ml i loksoribina od 34 μg/ml suboptimalna. Optimalne i suboptimalne koncentracije agonista su dalje korišćene za stimulaciju nezrelih MoDĆ u ovom istraživanju. Dendritic cells (DCs) are the most potent antigen presenting cells (APCs) which receive and integrate multiple signals to initiate and direct a response appropriate to extracellular milleu. These APCs perform these functions mostly due to the expression of a wide variety of pattern recognition receptors (PRRs). PRRs discriminate self-tissues from infectious non-self tissues through molecular pattern (MPs) recognition. Although triggering of a single pattern recognition receptor (PRR), especially Toll-like receptors (TLRs) or C-type lectins, results in phenotypic changes in DCs, for functional maturation cooperativity between multiple PRRs is needed in order to achieve an effective immune response. Recent studies have shown that the ligation of Dectin-1, C-type lectin receptor, on MoDCs elicits their maturation. Dectin-1, a DC-associated C-type lectin, is the first of many PRRs which mediate their own signaling and induces the maturation of DCs capable of eliciting the generation of different T helper (Th) effectors. The next aim of this work was to study the response of MoDCs to the combined effect of Poly (I:C) and curdlan, selective Dectin-1 agonists. Tumor necrosis factor (TNF)-α is important for early DC maturation and as a bridge between initiation of the inflammatory cascade and generation of the antigen-specific response. To gain insight into this scientific problem we investigated the kinetics of maturation and the length of exposure of MoDCs to a pathogen (mimicked by Poly (I:C) in our study) in an inflamed tissue (mimicked by TNF-α) on phenotypic and functional characteristics of MoDCs. Finally, little is known about how subsequent interaction of MoDCs with T cell-derived stimuli, such as CD40 or interferon-γ (IFN-γ), modulates MoDC functions. Therefore, this problem was the last objective of this study. Methods. Immature MoDCs (iMoDCs), generated from human monocytes, were treated with Poly (I:C) alone or in combination with loxoribine, curdlan or TNF-α for 48h. To investigate the influence of T-cell derived stimuli, MoDCs cultivated for 24h with Poly (I:C) alone or in combination with TNF-α were incubated either with CD40 ligand (L)-transfected J558 cells, soluble CD40L or IFN-γ for additional 24h. To examine the influence of kinetics of activation on the Th polarizing capability of MoDCs, we stimulated MoDCs with different doses of Poly (I:C) in combination with TNF-α for 24h and 48h. Phenotypic characteristics of MoDCs were determined by flow cytometry. Allostimulatory capability of MoDCs was tested using a mixed leukocyte reaction assay. Cytokine production was measured by ELISA and FlowCytomix. Results. Optimal concentration of Poly (I:C) stimulated the maturation of MoDCs as judged by the up-regulation of HLA-DR, CD86, CD40, CD54, CD83 and CCR7 expression. Poly (I:C)-treated MoDCs were potent producers of interleukin (IL)-12, moderate producers of IL-23 and weak producers of IL-10, which was followed by high production of IFN-γ and moderate production of IL-17 by allogeneic CD4+ T cells. In preliminary experiments iMoDCs were treated with Poly (I:C) (5 μg/ml, 10 μg/ml, 25 μg/ml and 50 μg/ml), loxoribine (34 μg/ml and 85 μg/ml) or curdlan (10 μg/ml , 50 μg/ml, 100 μg/ml and 200 μg/ml). Based on phenotypic characteristics and functional capabilities of MoDCs, the concentrations of Poly (I:C) (25 μg/ml), loxoribine (85 μg/ml) and curdlan (100 μg/ml) were found to be optimal for activation of MoDCs, while the concentrations of Poly (I:C) (10 μg/ml) and loxoribine (34 μg/ml) were found to be suboptimal. For stimulation of iMoDCs we used these concentrations of the agonists. The combined treatment of MoDCs with suboptimal concentrations of TLR3 and TLR7 agonists resulted in slight potentiation of HLA-DR, CD86, CD83, CD54 and CD40 molecules and stimulation of IL-27, IL-23 and IL-10 secretion, compared to effects of single agonists. This was followed by up-regulated secretion of IFN-γ and IL-17 in the co-culture with allogeneic CD4+ T cells. When the suboptimal concentration of Poly (I:C) was combined with the optimal concentration of loxoribine, MoDCs down-regulated HLA-DR and up-regulated CD86 expression, enhanced the production of IL-12 and IL-23 and down-regulated the levels of IL-10 and IL-27, compared to the effects of single agonists. MoDCs pretreated in this way stimulated the production of IFN-γ and lowered the levels of IL-4 and IL-10 by CD4+ T cells. The treatment of MoDCs with optimal concentrations of both TLR agonists was followed by down-regulation of HLA-DR, CD83 and CD40 expression and augmented the production of IL-12, IL-27 and IL-10, whereas the level of IL-23 was significantly lower, compared to relevant controls. These MoDCs promoted the production of IFN-γ and inhibited the production of IL-4, IL-10 and IL-17 in co-culture, compared to the effect of corresponding controls. The combination of Poly (I:C) and curdlan induced phenotypic maturation of MoDCs with the capability to stimulate alloreactive response. Such treated MoDCs up-regulated the production IL-12, IL-23 and IL-10, compared to the effect of Poly (I:C), alone. The opposite effect was observed for IFN-γ production. When combined, these agonists primed MoDCs to further increase the production of IFN-γ by CD4+ T cells in co-culture, especially those of naïve (CD45RA+) phenotype, and IL-17 by memory (CD45RO+) CD4+ T cells. Univerzitet u Beogradu Biološki fakultet Čolić, Miodrag Božić, Biljana Vučević, Dragana 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=8 https://fedorabg.bg.ac.rs/fedora/get/o:2129/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41187855 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:9 2013-09-19T00:00:00Z 1

Floristička, taksonomska i ekološka istraživanja dezmidnih algi Srbije Floristical, taxonomical and ecological study of desmid algae in Serbia Fužinato, Sanja I. dezmidne alge, Srbija, tresave, akumulacije, biodiverzitet desmid algae, Serbia, peat-bogs, reservoirs, biodiversity Datum odbrane: 8.6.2012. Doktorska disertacija obuhvata istraživanja dezmidnih algi na teritoriji Srbije. Algološki uzorci (299) za ovo istraživanje sakupljeni su u periodu od 2007. do 2011. godine sa 37 lokaliteta. Istraživanje je obuhvatilo različite tipove vodenih staništa: tresave, veštačke akumulacije, slane bare i ribnjake. Sa najvećeg broja lokaliteta sakupljano je više uzoraka iz različitih zajednica algi: planktona, bentosa, epifita. U radu je data sinonimika i opis svih zabeleženih taksona dezmidnih algi na teritoriji Srbije od 1883. godine do danas, tip staništa koja naseljavaju i rasprostranjenje u Srbiji. Pregledom literaturnih podataka i uzoraka sakupljenih ovim istraživanjem ustanovljeno je prisustvo 611 taksona dezmidnih algi na teritoriji Srbije, od čega je u ovom istraživanju utvrđeno 244 taksona iz 23 roda. Svi do sada zabeleženi taksoni dezmidnih algi svrstani su u 5 familija sa 25 rodova. Najveći broj taksona je utvrđen u rodovima Cosmarium (250), Staurastrum (102) i Closterium (86). Prvi put je za floru algi Srbije zabeleženo prisustvo dva nova roda (Cosmocladium i Heimansia) sa ukupno 3 nove vrste. Prvi put je za floru algi Srbije zabeleženo 69 taksona dezmidnih algi. Rodovi sa najvećim brojem novih taksona za floru algi Srbije su Cosmarium (25), Staurastrum (12) i Closterium (9). Pripadnici dezmidnih algi su nađeni u svim ispitivanim uzorcima. Statističkom obradom podataka utvrđeno je da postoji značajna korelisanost između trofičnosti i kiselosti staništa sa strukturom zajednica dezmidnih algi na istraživanim lokalitetima. The work compements and develops investigations on the desmid algae of Serbia. Algological samples (299) for this study were collected from 37 localities during the years 2007-2011. The samples of phytoplankton, benthos and epiphyte were collected from pit bogs, reservoirs, salt marshes and fish ponds. Detailed description of all desmid taxa which were found in Serbia since 1883 as well as their distribution in Serbia, habitats and saprobities are given. Total of 611 desmid taxa were rocorded for the territory of Serbia, 244 of which are dealt with in this work. All desmid taxa were classified in 5 families with 25 genera. The most numerous genera are Cosmarium (250), Staurastrum (102) and Closterium (86). For the first time two new genera (Cosmocladium and Heimansia) with 3 new species have been recorded in Serbia. The presence of 69 desmid taxa have been recorded for the fisrt time for territory of Serbia. The most numerous genera were Cosmarium (25), Staurastrum (12) and Closterium (9). In this investigation desmids have been found in all collected samples. Statistical research were shown that there are significant correlation between trophic status and acidity of water with structure of desmids community. Univerzitet u Beogradu Biološki fakultet Cvijan, Mirko Simić, Snežana Krizmanić, Jelena) 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=9 https://fedorabg.bg.ac.rs/fedora/get/o:2130/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41192463 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:10 2014-02-13T00:00:00Z 1

Analiza prirode rezistencije na hinolone i molekularna tipizacija odabranih serotipova Salmonella enterica subspecies enterica Analysis of nature of resistance to quinolones and molecular typing of selected serotypes of Salmonella enterica subspecies enterica Kozoderović, Gordana V., 1969- Salmonella Enteritidis, RAPD, rezistencija, hinoloni, gyrA, QRDR Salmonella Enteritidis, RAPD, resistance, quinolones, gyrA, QRDR Datum odbrane: 14.6.2012. Salmoneloze spadaju među najznačajnije zoonoze u svetu. S obzirom da se ljudi zaražavaju najčešće putem konzumacije hrane životinjskog porekla, nadzor nad salmonelama neophodan je u svakom stadijumu proizvodnje hrane od farme do viljuške. Širenje rezistencije na hinolone među salmonelama predstavlja veliki javno zdravstveni problem zbog uticaja na lečenje ljudi i životinja. Cilj istraživanja je bio da se ispita mogućnost brze i efikasne tipizacije Salmonella enterica subspecies enterica serotip Enteritidis (S. Enteritidis) kao najčešćeg serotipa kod ljudi i učestalost i molekularni mehanizmi rezistencije na hinolone kod salmonela. U kolekciji izolata S. Enteritidis poreklom od ljudi, pilića i iz namirnica živinskog porekla, kombinacijom RAPD-PCR tipizacije sa četiri prajmera, rezistotipizacije i polimorfizma mutacija u regionu gyrA gena koji kodira rezistenciju na hinolone (QRDR), diskriminisano je 22 genetičke grupe sa indeksom diskriminacije 0.828. Svi izolati bili su visoko srodni, a tipizacija je dokazala nasumičnu raspoređenost tipova u sve tri kategorije izolata, odnosno cirkulaciju sojeva kroz razne stadijume lanca ishrane. RAPD-PCR tipizacija uspešno je izdvojila epidemijski soj među tri izolata S. Enteritidis iz jednog restorana brze hrane. Analizom uzoraka iz fabrike biskvita ustanovljena je kontaminacija sa najmanje četiri soja S. Enteritidis i povezanost serotipa Enteritidis sa jajima kao izvorom kontaminacije. Analizom većeg uzorka izolata poreklom od namirnica i ljudi sa teritorije Južnobačkog okruga u šestogodišnjem periodu ustanovljena je mala učestalost rezistencije S. Enteritidis na antibiotike, retka pojava višestruke rezistencije na antibiotike i mala učestalost rezistencije na hinolone (2.9%). Nađena su tri tipa mutacija odgovornih za rezistenciju na hinolone u QRDR regionu: Asp87Asn, Asp87Gly i Ser83Phe. Dominirale su mutacije na 87. poziciji i to Asp87Asn supstitucija. Nisu nađeni dokazi o klonalnom širenju sojeva rezistentnih na nalidiksičnu kiselinu. Rezistencija na fluorohinolone nije otkrivena. Dokazana je smanjena osetljivost na fluorohinolone kod S. Enteritidis rezistentnih na nalidiksičnu kiselinu. Kod drugih serotipova salmonela rezistencija na nalidiksičnu kiselinu i udruženost sa više markera rezistencije bila je učestalija nego kod S. Enteritidis, naročito kod S. Hadar. Rezistencija na ampicilin i nalidiksičnu kiselinu bile su najčešće kod salmonela bez obzira na serotip. Diskriminativna moć i jednostavnost RAPD-PCR metode sa četiri prajmera udružene sa rezistotipizacijom preporučuju ih kao efikasan sistem tipizacije prilikom nadzora nad kretanjem salmonela u humanoj i životinjskoj populaciji. Ispitivanje rezistencije na antibiotike, a naročito na hinolone kod salmonela neophodno je u cilju upozoravanja kliničara na terapijske rizike, a sa epidemiološkog aspekta, radi detekcije pojave i širenja opasnih sojeva. Salmonelloses are among most significant zoonoses in the world. Since people are most often infected by consumption of food of animal origin, surveillance of salmonella is necessary in every stage of food production from farm to fork. Emergence of resistance to quinolones among salmonella is a significant public health problem, considering implications on the treatment of humans and animals. The aims of the investigation were to analyze the possibility of fast and efficient typing of Salmonella enterica subspecies enterica serotype Enteritidis (S. Enteritidis) as the most frequent serotype in humans and to investigate frequency and molecular mechanisms determining resistance to quinolones in salmonella. In a collection of S. Enteritidis isolates originating from humans, poultry and marketed poultry products and eggs, a combination of RAPD-PCR typing with four primers, resistotyping and polymorphism of mutations in quinolone resistance determining region (QRDR) of gyrA gene revealed 22 genetic groups with discrimination index of 0.828. All isolates were closely related and typing has proved random distribution of types in all three categories of isolates, ie. circulation of strains through subsequent stages of food chain. RAPD-PCR typing succesfully discriminated epidemic strain among 3 S. Enteritidis isolates from one fast food restaurant. Analysis of samples from one biscuit factory showed contamination with at least four strains of S. Enteritidis and strong connection of serotype Enteritidis with eggs as a source of contamination. Analysis of larger collection of isolates from food and humans in Southern Bačka county in a six-year period revealed low frequency of resistance of S. Enteritidis to antibiotics, rare occurence of multiple resistance to antibiotics and low frequency of resistance to quinolones (2.9%). Three types of mutations determining resistance to quinolones in QRDR were discovered: Asp87Asn, Asp87Gly and Ser83Phe. Mutations at position 87 are dominant, with Asp87Asn as the most frequent. There was no evidence of clonal spread of strains resistant to quinolones. Resistance to fluoroquinolones was not detected. Reduced susceptibility to fluoroquinolones among S. Enteritidis resistant to nalidixic acid was proved. Resistance to nalidixic acid and association with multiple antibiotic resistance were more common among other serotypes of salmonella, especially in S. Hadar, than among S. Enteritidis. Resistance to ampicillin and nalidixic acid were the most common in all investigated salmonella serotypes. Discriminative power and simplicity of RAPD-PCR method with four primers together with resistotyping recommend them as the efficient typing system for monitoring of salmonella in human and animal population. Investigation of resistance to antibiotics, especially to quinolones among salmonella is essential for alerting clinicians for therapy risks, and from epidemiological aspect, for detection of emergence and spread of dangerous strains. Univerzitet u Beogradu Biološki fakultet Milošević, Vesna Lozo, Jelena Velhner, Maja Golić, Nataša Strahinić, Ivana 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=10 https://fedorabg.bg.ac.rs/fedora/get/o:2131/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41188623 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:11 2013-09-19T00:00:00Z 1

Tkivna specifičnost efekata 17ß-estradiola na signalni put insulina Tissue specificity of 17ß-estradiol effects on insuli signaling pathway. Milosavljević, Tijana M. Estradiol, insulinski signalni put, jetra, uterus, srce Estradiol, insulin signaling, liver, uterus, heart Datum odbrane: 14.6.2012. Insulin i estradiol imaju va.nu ulogu u regulaciji metabolizma ugljenih hidrata i lipida. Razli.ita klini.ka istra.ivanja i eksperimentalni podaci ukazuju da varijacije u koncentraciji estrogena uti.u na insulinsko delovanje. Cilj ove studije je bilo pore.enje uticaja estradiola na po.etne molekule insulinskog signalnog puta u glavnim ciljnim tkivima za insulin (jetra) i estradiol (uterus), kao i u srcu, u kome oba hormona ostvaruju zna.ajne efekte. Ovarijektomisane .enke pacova su tretirane estradiolom 6 h pre analize sadr.aja proteina i iRNK molekula signalnog puta insulina. Da bi se istakli efekti estradiola na fosforilacije i asocijacije molekula relevantne za insulinski signalni put, .ivotinje su dodatno injecirane insulinom 30 min pre eksperimenta. Tretman estradiolom nije promenio nivo insulina i glukoze u plazmi, ali je doveo do zna.ajnog smanjenja nivoa slobodnih masnih kiselina i pove.anja te.ine uterusa. U jetri, tretman estradiolom je doveo do smanjenja fosforilacije IR, kao i smanjenja proteinskog sadr.aja IRS-1, .to navodi na zaklju.ak da je estradiol suprimirao efekte insulina preko IR/IRS-1 puta i verovatno ih usmerio na alternativni put, .to je potkrepljeno i pove.anjem proteinskog sadr.aja IRS-2. U uterusu je tretman estradiolom nakon 6 h doveo do statisti.ki zna.ajnog pove.anja proteinskog sadr.aja skoro svih ispitivanih molekula signalnog puta insulina. U srcu je estradiol uzrokovao pove.anje asocijacije IRS-1/p85, pove.anja sadr.aja proteina i iRNK p85, kao i pove.anje fosforilacije Akt na Ser473. S druge strane, tretman estradiolom je u srcu izazvao i smanjenje fosforilacije tirozina IR, smanjenje proteinskog sadr.aja IRS-2 i iRNK oba IRS proteina. Rezultati ove studije ukazuju na to da tretman estradiolom indukuje tkivno specifi.ne promene u insulinskom signalnom putu. Posledice tretmana estradiolom na molekule insulinskog signalnog puta su o.iglednije u uterusu, ali je njihov fiziolo.ki zna.aj za insulinsko delovanje verovatno ve.i u jetri. S druge strane, rezultati dobijeni u srcu sugeri.u veoma kompleksnu ulogu estradiola u fiziologiji srca, koja se manifestuje i kombinacijom pozitivnog i negativnog, genomskog i negenomskog delovanja ovog hormona na molekule signalnog puta insulina. Insulin and estradiol play important role in regulation of carbohydrate and lipid metabolism. Various clinical observations and experimental data suggest that variations in the concentration of estrogens affect insulin action. The aim of the present study was to compare the impact of estradiol on early steps of insulin signaling in main target tissues of insulin (the liver) and estradiol (the uterus), and in the heart, where both hormones realize important effects. Ovariectomized female rats were treated with estradiol 6 h prior to analysis of protein and mRNA content of insulin signaling molecules. To delineate estradiol effects on phosphorylations and molecular associations relevant for insulin signaling, animals were treated additionally with insulin 30 min before the experiment. Treatment with estradiol did not change the levels of plasma insulin and glucose, but it significantly decreased the free fatty acid level and increased uterine weight. In liver, estradiol treatment decreased IR phosphorylation and IRS-1 protein content, suggesting that estradiol suppressed insulin action through IR/IRS-1 and probably redirected it to alternative pathway. This conclusion is supported with increase of IRS-2 protein content. In uterus, estradiol treatment resulted in significant increase of protein content of almost all analyzed molecules. In heart, estradiol increased IRS-1/p85 association, p85 protein and mRNA level, and Ser473Akt phosphorylation. On the other hand, estradiol treatment decreased tyrosine phosphorylation of cardiac IR, protein content of IRS-2, and mRNA of both IRS proteins. These results suggest that estradiol treatment induces tissue-specific changes in insulin signaling. Consequences of estradiol treatment on insulin signaling molecules are more apparent in uterus, but their physiological relevance for insulin action is probably more important in liver. On the other hand, results obtained in heart suggest very complex role of estradiol in heart physiology, represented by, amongst other effects, combination of positive and negative, genomic and nongenomic actions of this hormone on insulin signaling molecules. Univerzitet u Beogradu Biološki fakultet Korićanac, Goran Cvijić, Gordana Žakula, Zorica 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=11 https://fedorabg.bg.ac.rs/fedora/get/o:2124/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41193231 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:12 2013-09-19T00:00:00Z 1

Identifikacija genskih lokusa (QTL) uključenih u kontrolu odgovora kukuruza (Zea mays L.) na stres suše Identification of quantitative trait loci (QTLs) for drought tolerance response in maize (Zea mays L.) Nikolić, Ana S. Kukuruz, tolerantnost na sušu, QTL-ovi Maize, drought tolerance, QTLs Datum odbrane: 15.5.2012. Suša je jedan od najvažnijih ogranicavajucih faktora u proizvodnji kukuruza, pa je poboljšanje tolerantnosti na sušu od veoma velikog znacaja u programima oplemenjivanja. Stvaranje genotipova tolerantnih na sušu je veliki izazov zbog variranja u pojavljivanju, intenzitetu i trajanju stresa suše, zbog geneticke kompleksnosti ovog stresa i izraženih interakcija genotip-sredina. Identifikacija kvantitativnih lokusa vezanih za tolerantnost na sušu je važno sredstvo za indirektnu selekciju pomocu molekularnih markera. Istovremena primena konvencionalnog sa molekularnim oplemenjivanjem, marker-asistiranom selekcijom i genetickim inžinjeringom može doprineti bržem nacinu za poboljšanje tolerantnosti na sušu kod gajenih biljaka. Identifikacija lokusa za kvantitativna svojstva (QTL) za tolerantnost na sušu kod kukuruza je urađena na genetickom materijalu dobijenom ukrštanjem linija DTP79 (izvor tolerantnosti na sušu) i B73 (linija osetljiva na sušu). Za konstruisanje molekularne mape neophodne za identifikaciju QTL-ova, korišcena je F2 generacija (John Innes Centre (JIC), Norwich, United Kingdom). Podaci o vrednostima svojstava potencijalno ukljucenih u odgovor kukuruza na stres suše su dobijeni analizom F3 familija u poljskim ogledima. Molekularna mapa i dobijene vrednosti za ispitivana svojstva su korišcene za detekciju QTL-ova. Na osnovu informacija o QTL-ovima je vršeno utvrivanje postojanja uzrocne povezanosti izmeu dva ili više svojstava. Fenotipske korelacije su izracunate primenom Pearson-ovog koeficijenta i bile su visoko znacajne za izvestan broj ispitivanih osobina. Identifikacija QTL-ova je uraena primenom ANOVA metode i metoda statistickog programa WinQTL karotgrafera, v 2.5. Prikazani su samo rezultati dobijeni primenom CIM (WinQTL karotgrafer, v 2.5) i ANOVA metode. Za ispitivanih 26 osobina primenom CIM metode je detektovano 147 QTL-ova, od kojih je 93 detektovano i primenom ANOVA metode. Ukupna fenotipska varijabilnost objašnjena identifikovanim QTL-ovima za sva analizirana svojstva je bila u ospegu od 11.85% (RSV) do 91.16% (ŠL3). Detektovani su hromozomski regioni u kojima se preklapaju QTL-ovi za pojedine osobine, koje su istovremeno pokazale i znacajnu meusobnu fenotipsku korelaciju, što ukazuje na moguce postojanje vezanih gena ili plejotropnih efekata koji uticu na ove osobine. Neki od detektovanih QTL-ova su identifikovani i u radovima drugih autora, na istoj poziciji u genomu kukuruza, što znaci da su oni zajednicki razlicitom genetickom materijalu. Ovi QTL-ovi mogu biti od znacaja u ekspresiji ispitivanih svojstava, ukazujuci na mogucnost njihovog uspešnog korišcenja u marker - asistiranoj selekciji. Drought is one of the most important limiting factors in maize production. Improving drought tolerance is therefore of outmost importance for breeding. Achieving this goal is a big challenge due to the variability in timing, intensity and duration of drought, genetic complexity of drought tolerance and large genotype by environment interactions. Identification of quantitative loci for drought tolerance is very imporatant for indirect selection using molecular markers. Conventional breeding together with molecular breeding, marker-assisted selection and genetic engineering could contribute to drought tolerance improvement of cultivated plants. Quantitative trait loci (QTLs) for drought tolerance were identified in a maize population derived from a cross between two lines - DTP79 (drought tolerant) and B73 (drought sensitive). Map construction (John Innes Centre (JIC), Norwich, United Kingdom) was done using F2 generation and the coresponding F3 progenies were evaluated for the traits potentialy related to drought tolerance in field trials. Phenotypic and marker data were used for QTL detection. Possible causal relationships between two or more traits were determined according to information about QTLs. Phenotypic correlations calculated using Pearson’s coefficients were highly significant for some of the analyzed traits. ANOVA and methods of WinQTL Cartographer 2.5 were employed to identify QTLs. Results of ANOVA and CIM option in WinQTL cartographer, v 2.5 are presented. A total of 147 QTLs were detected using CIM for the analyzed traits. Out of this number, 93 were also detected using ANOVA. Percent of phenotypic variability determined for the identified QTLs for all of the traits ranged from 11.85% (RWC) up to 91.16% (LW3). Mapping analysis identified genomic regions associated with two or more traits in a manner that was consistent with phenotypic correlation between traits, supporting the possible existence of linked genes or pleiotrophy that influence these traits. Some of the QTLs mapped herein, were also identified in the works of other authors, at the same position in the maize genome, indicating that they could represent regions that are common to various populations. These QTLs may be important in the expression of the traits, indicating the possibility of their successful use in marker-assisted selection. Univerzitet u Beogradu Biološki fakultet Stamenković-Radak, Marina Ignjatović-Micić, Dragana Quarrie, Steve A. Anđelković, Violeta 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=12 https://fedorabg.bg.ac.rs/fedora/get/o:2125/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024479154 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:13 2013-09-19T00:00:00Z 1

Parametri antioksidacione zaštite u tkivima nekih vrsta slatkovodnih riba iz jezera Gruža Antioxidant defence parameters in tissues of some species of freshwater fish from the Gruža reservoir Perendija, Branka R. Parametri antioksidacione zaštite, slatkovodne ribe, jetra, škrge, mišić, cvetanje cijanobakterija, jezero Gruža Antioxidant defence parameters, freshwater fish, liver, gills, muscle, cyanobacterial bloom, Gruža Reservoir Datum odbrane: 15.6.2012. Ribe mogu direktno da budu izložene toksinima cijanobakterija i zato su veoma dobri modeli za proučavanje uticaja cijanotoksina na ćelijski antioksidacioni sistem zaštite. Postoji mnogo informacija o biohemijskim i ultrastrukturnim promenama u različitim tkivima riba nakon izlaganja cijanotoksinima u laboratorijskim uslovima, ali su podaci o dejstvu cvetanja cijanobakterija u prirodnim uslovima veoma retki. Cilj ove doktorske disertacije bio je da se istraži uticaj cvetanja cijanobakterija u akumulacionom jezeru Gruža na parametre antioksidacione zaštite u jetri, škrgama i mišiću kod slatkovodnih vrsta riba Rutilus rutilus (bodorka), Blicca bjoerkna (blika), Carassius gibelio (babuška) i Perca fluviatilis (grgeč). Određivani su aktivnost enzima antioksidacione zaštite: ukupne, mangan i bakar cink sadržavajuće superoksiddismutaze (Uk SOD, Mn SOD, CuZn SOD, EC 1.15.1.1), katalaze (CAT, EC 1.11.1.6), glutation-peroksidaze (GSH-Px, EC 1.11.1.9), glutation-reduktaze (GR, EC 1.6.4.2) i enzima faze II biotransformacije glutation-S-transferaze (GST, EC 2.5.1.18), kao i koncentracija ukupnog glutationa (GSH) i sulfhidrilnih (SH) grupa. Histopatološka analiza jetre riba proučavana je na nivou svetlosne i elektronske mikroskopije. Svi ispitivani parametri mereni su pre i tokom cvetanja cijanobakterija... Dobijeni rezultati su pokazali da cvetanje cijanobakterija indukuje odgovor na oksidacioni stres u ispitivanim tkivima riba i dovodi do ultrastrukturnih promena u jetri. Rezultati ove doktorske disertacije predstavljaju prvi izveštaj o uticaju cvetanja cijanobakterija u akumulacionom jezeru Gruža na parametre antioksidacione zaštite (aktivnost SOD, CAT, GSH-Px, GR i enzima faze II biotransformacije GST, kao i koncentraciju GSH i SH grupa) u jetri, škrgama i mišiću slatkovodnih riba Rutilus rutilus, Blicca bjoerkna, Carassius gibelio i Perca fluviatilis. Biomonitoring antioksidacionih biomarkera u tkivima riba može da posluži kao rani upozoravajući signal koji ukazuje na oštećenja ćelija usled izloženosti cijanotoksinima u slatkovodnim ekosistemima. Ova disertacija pruža veliki doprinos na polju ekofiziologije akvatičnih organizama. Since fish can be directly exposed to cyanobacterial toxins, they are very good models to study the influence of cyanotoxins on the cellular antioxidant defence system. There is much information on biochemical and ultrastructural alterations in different fish tissues after exposure to cyanotoxins under laboratory conditions, however, data on the effects of cyanobacterial blooms in natural conditions are very scarce. The aim of this doctoral dissertation was to investigate the influence of the cyanobacterial bloom in the Gruža Reservoir on the antioxidant defence parameters in the liver, gills and muscle of freshwater fish Rutilus rutilus (roach), Blicca bjoerkna (white bream), Carassius gibelio (prussian carp) and Perca fluviatilis (European perch). The activity of antioxidant defence enzymes: total, manganese and copper zinc containing superoxide dismutases (Tot SOD, Mn SOD, CuZn SOD, EC 1.15.1.1), catalase (CAT, EC 1.11.1.6), glutathione peroxidase (GSH-Px, EC 1.11.1.9), glutathione reductase (GR, EC 1.6.4.2) and the biotransformation phase II enzyme glutathione-S-transferase (GST, EC 2.5.1.18), as well as the concentrations of total glutathione (GSH) and sulphydryl (SH) groups were determined. Histopathological examination of fish liver was performed by light and electron microscopy. All investigated parameters were measured before and during cyanobacterial bloom... The presented results show that the cyanobacterial bloom-induced response to oxidative stress caused ultrastructural alterations in the liver. The results of this doctoral dissertation are a first report on the influence of the cyanobacterial bloom in the Gruža Reservoir on antioxidant defence parameters (SOD, CAT, GSH-Px, GR and biotransformation phase II enzyme GST activities, as well as concentrations of GSH and SH groups) in the liver, gills and muscle of freshwater fish Rutilus rutilus, Blicca bjoerkna, Carassius gibelio and Perca fluviatilis. Biomonitoring of antioxidant biomarkers in fish tissue could serve as an early warning signal of cellular damage resulting from exposure to cyanotoxins in freshwater ecosystems. This dissertation is an important contribution in the field of ecophysiology of aquatic organisms. Univerzitet u Beogradu Biološki fakultet Saičić, Zorica Cvijić, Gordana Pajović, Snežana B. Ognjanović, Branka. 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=13 https://fedorabg.bg.ac.rs/fedora/get/o:2126/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41105935 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:14 2013-09-19T00:00:00Z 1

Genetička transformacija kičice (Centaurium erythraea Rafn.) AtCKX1 i AtCKX2 genima Genetic transformation of Centaury (Centaurium erythraea Rafn.) using AtCKX1 and AtCKX2 genes Trifunović, Milana M. Centaurium erythraea Rafn., Agrobacterium tumefaciens, genetička transformacija, qRT-PCR, AtCKX geni, CKX aktivnost, citokinini, sekundarni metaboliti,sekoiridoidi, ksantoni Centaurium erythraea Rafn., Agrobacterium tumefaciens, genetic transformation, qRT-PCR, AtCKX genes, CKX activity, cytokinins, secondary metabolites, secoiridoids, xanthones Datum odbrane: 20.6.2012. Biljna vrsta Centaurium erythraea Rafn., u našem narodu poznata kao kičica, od davnina se upotrebljava kao lek za sniženje temperature i nivoa šećera u krvi, lečenje anemije, žutice i gihta, za jačanje apetita i povećanje stomačne sekrecije. Zbog poznatih lekovitih svojstava, kičica se nalazi u mnogim farmakopejama. Kao početni materijal za uspostavljanje kulture korenova in vitro korišćeni su vrhovi adventivnih korenova prosečne dužine ~10 mm koji su izolovani od sterilno dobijenih klijanaca kičice i dalje su gajeni na čvrstoj MS hranljivoj podlozi bez regulatora rastenja. Proces organogeneze u kulturi korenova kičice je spontan. Posle sedam dana gajenja u kulturi na bazalnom delu početnog eksplantata uočavaju se prve promene. Koren zadebljava i tkivo počinje da puca celom dužinom bazalnog dela. Tokom četvoronedeljnog pasaža, duž razraslog dela eksplantata, formira se veliki broj adventivnih pupoljaka. U cilju dobijanja transgenih biljaka sa sniženim nivoom endogenih citokinina, za transformaciju su korišćena dva bakterijska soja Agrobacterium tumefaciens GV3101 koji nose pBinHTX plazmid sa dva različita gena, AtCKX1 odnosno AtCKX2, koji kodiraju enzim citokinin oksidazu/dehidrogenazu (CKX). Efikasna integracija AtCKX1 gena (30% ) i AtCKX2 gena (28.2% ) određena je PCR analizom genomske DNK. U cilju što boljeg određivanja nivoa ekspresije AtCKX gena kičice prvo je bilo neophodno urađena je optimizacija PCR protokola sa prajmerima za qPCR. Ovaj postupak sastojao se u pronalaženju optimalne temperature vezivanja prajmera uz istovremenu primenu različitih aditiva odnosno pojačivača PCR reakcije. Dodavanje 5% DMSO-a u qPCR reakcije značajno je poboljšalo specifičnost amplifikacije AtCKX1 i AtCKX2 gena kičice. qRT-PCR analizom potvrđena je ekspresija AtCKX1 i AtCKX2 gena kod 50% odnosno 64% analiziranih linija. U ovom radu uspešno je pokazano da ekspresija AtCKX gena u transgenim biljkama kičice značajno utiče na metabolizam citokinina. Ključni faktor u kontroli nivoa citokinina u biljnim tkivima predstavlja CKX enzim, jedini do sada poznati enzim koji učestvuje u katabolizmu citokinina. Specifična aktivnost CKX enzima određivana je u izdancima i korenovima svih transgenih AtCKX linija. Analiza količine i sadržaja ukupnih kao i pojedinačnih grupa endogenih citokinina netransfromisanih biljaka kičice omogućila je, po prvi put, određivanje citokiniskog profila kičice in vitro... Plant species Centaurium erythraea Rafn., commonly known as common centaury, has been used for centuries to cure febrile conditions, regulate blood sugar, treat anemia, jaundice and gout and to increase appetite and stimulate digestion. Because of its numerous therapeutic properties centaurii herba is officially recognized as a drug in a number of pharmacopoeias. Root tips of .10 mm average length, isolated from seedlings obtained under sterile conditions, were used as initial explants in this work. The in vitro culture of non-transformed centaury roots was established on solid half-strength MS nutrient medium without growth regulators. Organogenesis is a spontaneous process in centaury root culture. The first changes were noticeable on the basal part of the initial explants, after seven days of growth on MS medium. The root explants thickened and began to burst over the entire length of the basal part. During four weeks of subculture, a large number of adventitious buds were observed on initial explants. In order to obtain transgenic centaury plants with lowered endogenous cytokinin levels, in vitro cultivated root explants were transformed with Agrobacterium tumefaciens GV3101 bearing a pBinHTX plasmid with either AtCKX1 or AtCKX2 genes encoding isoforms of cytokinin oxidase/dehydrogenase (CKX). PCR analysis of genomic DNA confirmed the effecient integration of both AtCKX1 (30%) and AtCKX2 (28.2%) genes. In order to investigate the expression of AtCKX genes in transgenic centaury plants, an optimization of PCR protocol with qPCR primers was necessary. Optimization of PCR protocol implicated finding the optimal annealing temperature and simultaneous application of different PCR additives and enhancers. Addition of 5% DMSO significantly improved the specificity of qPCR amplification of AtCKX1 and AtCKX2 genes. qRT-PCR analysis indicated that AtCKX1 and AtCKX2 genes were expressed in 50% and 64% of the analyzed transgenic lines, respectively. In this work we clearly demonstrate a significant effect of AtCKX genes on cytokinin metabolism in transgenic centaury plants. Since CKX is the only known enzyme involved in cytokinin catabolism, it is considered a key factor in controlling the cytokinin levels in plant tissues. CKX enzyme activity was determined in shoots and in roots of all AtCKX transgenic lines. The analysis of the content of total cytokinins and individual groups of endogenous cytokinins in non-transformed centaury plants enabled, for the first time, a determination of cytokinin profile of this species in vitro... Univerzitet u Beogradu Biološki fakultet Subotić, Angelina Dragićević, Ivana Simonović, Ana 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=14 https://fedorabg.bg.ac.rs/fedora/get/o:2091/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41189135 sr Autorstvo 3.0 Srbija (CC BY 3.0)

oai:eteze.bg.ac.rs:15 2013-09-19T00:00:00Z 1

Ekološka i toksikološka istraživanja crnomorske haringe (Alosa immaculata Bennett, 1835) u Dunavu u Srbiji Ecological and toxicological study of the Pontic shad (Alosa immaculata Bennett, 1835) in the Danube River in Serbia Višnjić-Jeftić, Željka V. crnomorska haringa, Dunav, hepatosomatski indeks, gonadosomatski indeks, kondicioni faktor, određivanje starosti kod riba, geometrijska morfometrija, teški metali i mikroelementi Pontic shad, Danube River, hepathosomatic index, gonadosomatic index, Fulton's condition factor, fish age determination, geometric morphometry, heavy metals and trace elements Datum odbrane: 18.6.2012. Crnomorska haringa (Alosa immaculata, Bennett 1835) je anadromna vrsta koja veći deo života provodi u jako zagađenom severoistočnom delu Crnog mora, a radi mresta migrira u Dunav. Populacije crnomorske haringe imaju opadajući trend brojnosti, tako da se prema IUCN Crvenoj listi ugroženih vrsta tretira kao ranjiva vrsta (VU). Njen migratorni put radi mresta skraćen je izgardnjom brane Đerdap II do 863 rkm Dunava. Iako je komercijalno značajna, istraživanja na crnomorskoj haringi sprovode se povremeno. Za izradu ovog rada, migranti crnomorske haringe prikupljeni su tokom aprila i maja 2004., 2006., 2007. i 2008. godine na 863 rkm Dunava, neposredno ispod brane Đerdap II. Struktura populacije u odnosu na dužinske klase i dužinsko-težinski odnosi analizirani su na osnovu merenja totalne dužine (TL) i ukupne težine tela (W) jedinki koje su sakupljene u 2004. i 2006. godini. Opseg variranja totalnih dužina tela ulovljenih jedinki iznosio je od 24,2 do 38,7 cm, sa dominacijom klase od 32-32,5 cm. Dobijeni faktori alometrije dužinsko-težinskog odnosa manji su od tri (b<3) za oba pola i za obe sezone uzoraka. Ova studija je imala za cilj da obezbedi i prve podatke o geometrijsko-morfometrijskim karakterima crnomorske haringe, vrednostima gonadosomatskog (GSI) i hepatosomatskog indeksa (HSI) kao i Fultonovog faktora kondicije (K) u Dunavu u Srbiji. Zabeležena je statistički značajna razlika između GSI, HSI i K između oba pola i u obe sezone uzorkovanja. Razlike nisu pronađene samo za vrednosti K između mužjaka i ženki u 2004. godini i za vrednosti GSI i K između ženki uzorkovanih u 2004. i 2006. godini... The Pontic shad (Alosa immaculata Bennett 1835) is an anadromous species that spends most of its life cycle in the heavily polluted northwestern part of the Black Sea and migrates into the Danube River to spawn. Populations of the Pontic shad have a declining trend, and according to the IUCN Red List of Threatened Species the species is classified as vulnerable (VU). Although its migratory way upstream the Danube is shortened to 863 rkm after the construction of the Iron Gate II dam and even though it represents a commercially important fish species in the lower section of the Danube, the research on the Pontic shad was performed only sporadically in this area. For the purpose of this study, Pontic shad migrants were collected during April and May 2004, 2006, 2007, and 2008, immediately downstream from the Iron Gate II dam. The length frequency distribution and length-weight relationship were determined according to the measured total body length (TL) and body weight (W) of individuals sampled in 2004 and 2006. The length-weight allometric factor (b) was lower than 3 (b<3) for both sexes and both sampling seasons. The length frequency ranged from 24.2 to 38.7 cm, with the domination of the length class of 32-32.5 cm. This study was also aimed at providing the very first data on geometric morphometrics, gonadosomatic index (GSI), hepatosomatic index (HSI), and Fulton's condition factor (K) of Pontic shad migrants from the Danube in Serbia. There were statistical differences in GSI, HSI, and K between males and females in both sampling seasons, except for K between males and females in 2004, and for GSI and K between females in 2004 and 2006... Univerzitet u Beogradu Biološki fakultet Krpo-Ćetković, Jasmina Hegediš, Aleksandara Lenhardt, Mirjana Jarić, Ivan 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=15 https://fedorabg.bg.ac.rs/fedora/get/o:2134/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024490674 sr Autorstvo-Nekomercijalno 3.0 Srbija (CC BY-NC 3.0)

oai:eteze.bg.ac.rs:16 2013-09-19T00:00:00Z 1

Biologija kozice Parapenaeus longirostris (Lucas, 1846) (Crustacea, Decapoda) na šelfu crnogorskog primorja Biology of the deep water pink shrimp Parapenaeus longirostris (Lucas, 1846) (Crustacea, Decapoda) on the Montenegrin shelf Marković, Olivera B. Parapenaeus longirostris, biologija, kočarski ribolov, šelf, prelov, Crnogorsko primorje, Južni Jadran Parapenaeus longirostris, biology, demersal trawl fishery, shelf, overexploited stock, Montenegrin coast, South Adriatic Datum odbrane: 11.6.2012. Jedna od najvažnijih komercijalnih vrsta dekapodnih rakova u kočarskom ribolovu na šelfu Crnogorskog primorja je kozica, Parapenaeus longirostris (Lucas, 1846). Istraživanje je obavljeno tokom dvije godine, od novembra 2006. do oktobra 2007. i od juna 2009. do maja 2010. godine pri čemu su uzorci uzimani sa kočarskih brodova mjesečnom dinamikom. Tokom prve godine je ukupno obrađeno 1979 jedinki, od kojih su 1421 (71.80%) bile ženke a 558 (28.20%) mužjaci. Odnos polova je i u drugoj godini bio u korist ženki tokom koje je analizirano 1967 jedinki, od kojih su 1304 (66.30%) bile ženke a 663 (33.70%) mužjaci. Raspon dužina karapaksa svih ulovljenih jedinki zajedno je bio manji u prvoj godini i kretao se od 15 do 37 mm (25.23 ± 4.48) dok je u drugoj taj raspon bio 11-37 mm (24.85 ± 4.48). Uočen je polni dimorfizam: ženke su u prosjeku i duže i teže od mužjaka, i u dužinskim grupama >28- 30 mm CL su 100% prisutne u ulovu. Mužjaci su u boljoj kondiciji od ženki. Vrijednosti alometrijskog koeficijenata b dužinsko-težinskog odnosa u prvoj godini iznose b = 2.58 za ukupan uzorak, b = 2.51 za ženke i b = 2.34 za mužjake; dok te vrijednosti za drugu godinu iznose b = 2.59 za ukupan uzorak, b = 2.57 za ženke i b = 2.33 za mužjake. Prva polna zrelost ženki je nastupila pri dužini karapaksa od 20.48 mm u prvoj godini, odnosno od 19.89 mm CL u drugoj godini... Parapenaeus longirostris (Lucas, 1846) is one of the most economically important decapod species in the trawl fishery on the Montenegrin shelf (southern Adriatic Sea). Despite its importance, there were no biological studies on the species for that area. Data were obtained from monthly samples taken from commercial catches realized in the southern Adriatic during the period from November 2006 to October 2007 and from June 2009 to May 2010. During the first year among the 1979 specimens, 71.80% were females and 28.20% males, while during the second year of investigation, among the 1967 specimens, 66.30% were females and 33.70% males. The overall sex ratio was in favour of females. The carapace length of all specimens ranged from 15 to 37 mm, with a mean of 25.23 ± 4.48, while during the second year the range of carapace length of all specimens was wider and ranged from 11 to 37 mm, with a mean of 24.85 ± 4.48. A marked sexual dimorphism was observed between males and females: females have a wider size range, greater size and weight. Percentage of females reached 100% in the 28-30 mm size class and beyond. Males were in better condition than females. The calculated allometric coefficient of length-weight relationships was b= 2.58 for the total sample of 2006-2007 year, b= 2.51 for females and b= 2.34 for males; while during the 2009-2010 values were b=2.59 for the total sample, b=2.57 for females and b=2.33 for males. The size at which 50% of the female population reached maturity was at a carapace length of 20.48 mm in the first year and 19.89 mm during the second year... Univerzitet u Beogradu Biološki fakultet Simonović, Predrag Nikolić, Vera Petrov, Brigita Regner, Slobodan Joksimović, Aleksandar 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=16 https://fedorabg.bg.ac.rs/fedora/get/o:2135/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024491186 sr Autorstvo-Nekomercijalno-Deliti pod istim uslovima 3.0 Srbija (CC BY-NC-SA 3.0)

oai:eteze.bg.ac.rs:17 2013-09-19T00:00:00Z 1

Molekulski mehanizmi strukturnog remodeliranja mrkog masnog tkiva pacova indukovanog insulinom Molecular mechanisms of insulin-induced rat brown adipose tissue structural remodelling Markelić, Milica B. Mrko masno tkivo, insulin, hiperinsulinemija, strukturno remodeliranje tkiva, adipogeneza, angiogeneza, termogeneza, mrki adipocit Brown adipose tissue, insulin, hyperinsulinaemia, structural tissue remodeling, adipogenesis, angiogenesis, thermogenesis, brown adipocyte Datum odbrane: 4.5.2012 U svetlu sve većeg broja dokaza koji ukazuju na prisustvo metabolički aktivnog mrkog masnog tkiva (BAT – brown adipose tissue, engl.) kod odraslih ljudi, kao i na njegovu potencijalnu ulogu u sprečavanju razvoja gojaznosti, insulinske rezistence i metaboličkog sindroma uopšte, sve je više studija o rasvetljavanju metaboličkog značaja ovog tkiva, kao i njegovoj termogenoj stimulaciji u svrhu terapije navedenih poremećaja. Insulin se, kao važan anabolički hormon, smatra značajnim modulatorom strukturne organizacije i funkcije BAT. Cilj ovog istraživanja bio je rasvetljavanje molekulskih osnova insulinomindukovanog strukturnog remodeliranja BAT putem identifikacije mehanizama koji regulišu insulinom-stimulisanu proliferaciju i diferencijaciju ćelija, kao i identifikacije mehanizama koji učestvuju u oštećenjima ćelija i njihovom umiranju. Pacovi soja Wistar su jednom dnevno tretirani fiziološkom (0.4 IU/kg telesne mase) i suprafiziološkom (4 IU/kg telesne mase) dozom insulina, jedan (akutan tretman) ili tri (hroničan tretman) dana. Kao fiziološka kontrola, dve grupe pacova su u istom trajanju tretirane fiziološkim rastvorom (akutna i hronična kontrola). Tri sata nakon poslednje doze, životinje su žrtvovane, a interskapularni depo BAT je izolovan, izmeren i pripremljen za tehnike svetlosne i elektronske mikroskopije. Analiza tkiva izvršena je korišćenjem metoda histohemijskog i imunohistohemijskog bojenja, metoda konfokalne i transmisione elektronske mikroskopije i elektron-disperzivne analize X-zracima (EDX) hemijskog sastava tkiva kao i metoda stereološke i morfometrijske analize. Rezultati su pokazali postojanje strukturnog i funkcijskog remodeliranja BAT, gde dominiraju procesi hipertrofije i hiperplazije ćelija, praćene povećanjem termogenog kapaciteta mrkih adipocita (raste ekspresija dekuplujućeg proteina 1 (UCP1 – uncoupling protein 1, engl.), udeo mitohondrija, procesi mitohondriogeneze). S druge strane, primetno je da se, naročito pri hroničnim i tretmanima visokom dozom insulina, javljaju citotoksični i inhibitorni efekti na pojedine ćelije ili klastere ćelija: raste učestalost ćelijske smrti, ekstravazacija eritrocita i njihovo uklanjanje od strane mrkih adipocita i makrofaga, (evidentno toksično po adipocite sudeći po rastu: ekspresije enzima antioksidativne odbrane; lipidne peroksidacije i nitrozilacije proteina, učestalosti lipofuscinogeneze). Takođe se pri hronično visokoj hiperinsulinemiji smanjuje ekspresija regulatora termogeneze (PGC-1α - peroxisome proliferator-activated receptor – γ coactivator - 1α, engl.) ukazujući da produženo izlaganje visokim dozama insulina, može da inhibira termogeni odgovor tkiva, o čemu svedoči i povećana učestalost mitohondrijalnih oštećenja. Povećana ekspresija proinflamatornih citokina (TNF-α - tumor-necrosis factor – α, engl., interleukina 6), nukleusnog faktora – kB (NF-kB) i makrofagnog inflamatornog proteina - 3β (MIP-3β) u pojedinačnim zrelim, multilokulusnim adipocitima, preadipocitima i unilokulusnim adipocitima ukazuje na njihovu potencijalnu ulogu u lokalnom smanjenju insulinske senzitivnosti. U vezi sa hiperplazijom ćelija, primećeno je da su adipogeneza i angiogeneza u BAT vremenski i prostorno povezane, tj. da postoji udruženost navedenih procesa, koja ukazuje na potrebu udruženog nastanka adipocita i endotelskih ćelija, u svrhu efikasnog strukturno-funkcijskog remodeliranja tkiva. Sumarno, može se zaključiti da hiperinsulinemija ima značajan efekat na BAT – potvrđeno je anaboličko dejstvo insulina i važnost njegove uloge u stimulaciji BAT, ali je i pokazana toksičnost visoke doze i hroničnog izlaganja na ćelije BAT; što je sve doprinelo rasvetljavanju molekulskih mehanizama u osnovi strukturnog remodeliranja ovog tkiva. Takođe, pokazano je da se visoka plastičnost BAT ogleda u postojanju funkcionalnih klastera ćelija, u kojima se odvijaju svi važni tkivni procesi (adipo/angiogeneza, ćelijska smrt, eritrofagocitoza), što ukazuje na pravilnu uređenost tkivne organizacije i strukturnog remodeliranja, kao preduslova za pravilno funkcionisanje tkiva, kako u fiziološkim, tako i u uslovima izmenjene tkivne homeostaze, što je pokazano na modelu hiperinsulinemije. There is an increasing amount of evidence that indicates presence of brown adipose tissue (BAT) in adult humans, and its potential role in prevention of obesity, insulin resistance and metabolic syndrom, in general. That is why number of studies on elucidation of the metabolic importance of this tissue, along with its thermogenic stimulation in order to treat these disorders, increases. As an important anabolic hormone, insulin is considered as a major modulator of BAT structure and function. The aim of this study was to elucidate the molecular basis of insulin-induced structural remodeling of BAT through the identification of mechanisms that regulate insulin-stimulated proliferation and differentiation and through the identification of mechanisms involved in cell damage and death. Wistar strain rats were treated intraperitoneally with physiological (0.4 IU/kg BW) or supraphysiological (4 IU/kg BW ) dose of insulin for one (acute treatment) or three days (chronic treatment), respectively. Two groups of rats served as physiological controls, and were treated with saline (acute and chronic control). Three hours after the last injection the animals were sacrificed and the interscapular portion of BAT was removed, its weight was measured and it was processed for electron and light microscopic examinations. Methods of histochemical staining, immunohistochemical labeling, confocal and transmission electron microscopy, tissue electron-dispersive X-ray microanalysis (EDX) and stereological and morphometric analyses were performed. The results showed the existence of structural and functional remodeling of BAT, based on adipocyte hypertrophy and hyperplasia which are followed by increasing of thermogenic capacity (expression of uncoupling protein 1 (UCP1), cellular proportion of mitochondria, mitochondrial biogenesis). On the other hand, it is obvious that, especially after chronic and high-dose treatments, insulin cytotoxic and inhibitory effects on individual cells or cell clusters occur: incidence of cell death increases, as well as red blood cell extravasation and their removal by brown adipocytes and macrophages (which is evidently toxic for the adipocyte, since expression of antioxidative defense enzymes, lipid peroxidation, protein nitrosilation and lipofuscin formation were increased). Also, during chronically high hyperinsulinemia, expression of peroxisome proliferator-activated receptor - γ coactivator - 1α (PGC-1α), regulator of thermogenesis decreases, indicating that prolonged exposure to high doses of insulin can inhibit thermogenic response of BAT, as evidenced by the increased frequency of mitochondrial damage in brown adipocytes. Increased expression of proinflammatory cytokines (tumornecrosis factor - α (TNF-α), interleukin 6), nuclear factor – kB (NF-kB) and macrophage inflammatory protein - 3β (MIP-3β) in individual mature, multilocular adipocytes, preadipocytes and unilocular adipocytes, demonstrates their potential role in local decrease of insulin sensitivity. Regarding hyperplasia of cells, it was noticed spaciotemporal association between processes of adipogenesis and angiogenesis, which means that there is a connection between these processes, demonstrating the need for the coupled differentiation of adipocytes and endothelial cells, for the purpose of efficient structural and functional remodeling of the tissue. In summary, it can be concluded that hyperinsulinemia has a significant impact on BAT – we confirmed the anabolic effect of insulin, and the importance of its role in BAT stimulation, but also demonstrated the toxicity of high dose and chronic exposure to insulin on BAT cells, all of which contribute to understanding the molecular mechanisms underlying structural remodeling of the tissue. In addition, it was shown that the high plasticity of BAT is reflected in the existence of functional clusters of cells, which take place in all the important processes in the tissue (adipo/angiogenesis, cell death, erythrophagocytosis), indicating the proper arrangement of tissue organization and structural remodeling as a prerequisite for the proper functioning of the tissue under physiological conditions and during altered tissue homeostasis, as shown on the model of hyperinsulinemia. Univerzitet u Beogradu Biološki fakultet Korać, Aleksandra Stančić, Ana Korać, Bato Janković, Aleksandra Buzadžić, Biljana 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=17 https://fedorabg.bg.ac.rs/fedora/get/o:2208/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024477618 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:18 2013-10-01T00:00:00Z 1

Оdrživi mеnаdžmеnt mеdiја u društvеnim kоnfliktimа i krizаmа Sustainable media management in social conflicts and crisis Kostić, Branislava J., 1956- Održivоst, mеdiјi, mеnаdžmеnt, društvеni kоnflikti, krizе, uticај mеdiја, mir, rаt Sustainability, media, management, social conflicts, crises, the impact of the media, peace, war Datum odbrane: 27.09.2012. Prеdmеt istrаživаnjа, u оvоm rаdu, је оdrživi mеnаdžmеnt mеdiја u uslоvimа društvеnih kоnflikаtа i krizа, krајеm dvаdеsеtоg i pоčеtkоm dvаdеsеtprvоg vеkа: оd rеvоluciје u Rumuniјi (dеcеmbаr 1989. gоdinе), kоја је prеdstаvlјаlа prеkrеtnicu u pоglеdu ulоgе mеdiја u društvеnim kоnfliktimа i krizаmа, dо dеcеmbrа 2009. gоdinе. Društvеni kоnflikti sе u rаdu pоsmаtrајu kао bitnа kаrаktеristikа istоriјskоg rаzvоја lјudskоg društvа, kоја nе mоrа biti nužnо imаnеntnа lјudskој zајеdnici nа svim nivоimа njеnоg rаzvоја. Nаučni cilј istrаživаnjа, u оvоm rаdu, је sticаnjе nоvih sаznаnjа о sаdаšnjеm i mоgućеm uticајu mеnаdžmеntа mеdiја nа humаnizаciјu lјudskih оdnоsа u оblаsti prеvеnciје, izbiјаnjа, tоkа i rаzrеšеnjа društvеnih kоnflikаtа i krizа, оdnоsnо - dоkаzivаnjе hipоtеzа pоstаvlјеnih u rаdu. Rеаlizаciја istrаživаnjа kоје imа оvаkо dеfinisаn cilј, nužnо pоlаzi оd аnаlizе sаdаšnjеg dеlоvаnjа mеdiја u društvеnim kоnfliktimа i krizаmа, kаkо bi sе dоšlо dо prојеkciје mоgućеg dеlоvаnjа. Društvеni cilј istrаživаnjа је dеfinisаnjе prеdlоgа Dеklаrаciје о оdrživim mеdiјimа u društvеnim kоnfliktimа i krizаmа, kао оsnоvе zа diskusiјu i dеfinisаnjе оsnоvnih еlеmеnаtа nаcrtа: а) kоdеksа pоnаšаnjа оdrživih mеdiја u društvеnim kоnfliktimа i krizаmа; b) kоdеksа оdrživоg mеnаdžmеntа mеdiја. Оpštа hipоtеzа, pоstаvlјеnа u rаdu, glаsi: "Оdrživi mеnаdžmеnt mеdiја u društvеnim kоnfliktimа i krizаmа mоžе imаti znаčајаn pоvоlјаn uticај nа humаnizаciјu lјudskih оdnоsа u оblаsti prеvеnciје, tоkа i rаzrеšеnjа društvеnih kоnflikаtа i krizа. Оdrživi mеnаdžmеnt mеdiја mоžе izvršiti znаčајаn pоvоlјаn uticај nа stеpеn pоštоvаnjа lјudskih prаvа i slоbоdа, smаnjеnjе nаsilја i intеnzivirаnjе nеnаsilnе kоmunikаciје tоkоm društvеnih kоnflikаtа i krizа, kао i nа humаnо rаzrеšеnjе kоnflikаtа i krizа i njihоvо prеduprеđivаnjе." (…) The research subject in this paper, is the sustainable management of the media in terms of social conflicts and crises in the late twentieth and early twenty-first century: from the revolution in Romania (December, 1989.), which was a turning point for the role of media in social conflicts and crises, till December 2009. Social conflicts are here seen as an essential characteristic of the historical development of human society, which is not necessarily inherent to the human community at all levels of its development. The scientific objective of the research in this paper is the acquisition of new knowledge about current and possible impact of media management on humanization of human relations in the areas of prevention, outbreak, course and resolution of social conflicts and crises, which will prove the hypothesis set out in the paper. Realization of research that has its objective defined in such manner, necessarily starts on the analysis of the current activity of the media in social conflicts and crises, in order to come to projections of possible exposure. Social objective of this research is defining a Declaration proposal for sustainable media in terms of social conflicts and crisis, as a basis for discusion and creation of a draft for: a) behaviour codex of sustainable media in social conflicts and crisis; b) sustainable media management codex. General hypothesis, set out in this paper, states: "Sustainable management of media in social conflicts and crises can have a significant beneficial impact on the humanization of human relations in the areas of prevention, course and resolution of social conflicts and crises. Sustainable Management of the media can make a significant favorable impact on the degree of human rights and freedoms, reduction of violence and intensification of non-violent communication in social conflicts and crises, also the humane resolving of conflicts and crises and their preclusion." (...) Univerzitet u Beogradu Fakultet bezbednosti Kešetović, Želimir M., 1960- Cvetković, Vladimir N., 1961- Valić Nedeljković, Dubravka, 1952- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=18 https://fedorabg.bg.ac.rs/fedora/get/o:2213/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41091343 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:22 2013-09-25T00:00:00Z 1

Ekološka istraživanja juvenilnog inćuna, Engraulis encrasicolus (Linnaeus, 1758) u Kotorskom zalivu Ecological study of the juvenile anchovy, Engraulis encrasicolus (Linnaeus, 1758) in the Bay of Kotor Đurović, Mirko A. 1976- Inćun, Kotorski zaliv, populaciona dinamika, otoliti, reproduktivne karakteristike, biomasa Anchovy, Bay of Kotor, population dynamics, otoliths, reproductive characteristics, biomass Datum odbrane: 13.07.2012. U ovoj disertaciji prikazani su rezultati dvogodišnjeg istraživanja ekoloških karakteristika juvenilnog inćuna, Engraulis encrasicolus (L.), na području Kotorskog zaliva. S obzirom da se ribolov ove vrste na području Kotorskog zaliva obavlja tradicionalnom metodom, korišćenjem mreža potegača sa vrlo malim okom na mreži (6 mm), koja ima viševjekovnu tradiciju, jedan od glavnih ciljeva bio je da se odredi da li se može i u kojoj mjeri dozvoliti ovaj tip ribolova a da se ne ugrozi populacija inćuna na području Kotorskog zaliva. Uzorkovanje je vršeno iz komercijalnih ulova mrežama potegačama u periodu jun 2004. – jul 2005. godine i jul 2006. – jun 2007. godine. Analizirano je ukupno 4203 jedinki inćuna. U analiziranim ulovima inćun je u obije istraživane godine bio zastupljen sa 37%, dok je ulov po jedinici napora (CPUE) iznosio 150 kg po potezu. Struktura istraživane populacije inćuna u odnosu na dužinske klase kretala se u rasponu od od 5,2 do 13,2 cm, sa srednjom dužinom od 8,6 cm. Faktor alometrije dužinsko-težinskog odnosa za cjelokupan analiziran uzorak iznosi b = 3,122, dok se vrijednost faktora kondicije kretala u rasponu od 0,981 do 1,017, sa srednjom vrijednošću od 1,003 ± 0,009. Po prvi put su na ovom području, i uopšte na južnom Jadranu, analizirani otoliti juvenilnog inćuna i određena je starost u danima. Na osnovu očitavanja otolita izračunati su parametri rasta (L∞ = 10,41, K = 3,36 i t0 = -0,074 ), i određena je dužina pri kojoj dolazi do metamorfoze iz larvalnog u juvenilni stadijum (32,41 mm), a takođe je određena i dnevna stopa rasta juvenilnog inćuna (0,41 mm/danu). Izračunati su i brzina rasta otolita i njihova asimptotska dužina (L∞ = 1918 μm), dok je maksimum rasta otolita 62 dana nakon izlijeganja jedinke. Procenjeni parametri rasta za juvenilni dio populacije modalnom progresijom iznose L∞ = 9,21, K = 4,51 i t0 = -0,04 za period 2004-2005. godine i L∞ = 10,94, K = 2,25 i t0 = -0,175 za period 2006-2007. godine. Istom metodom procijenjeni su i parametri rasta za cijelu populaciju inćuna, i to za period istraživanja 2004-2005. V godine (L∞ = 15,41, K = 0,59 i t0 = -0,761 ), odnosno 2006-2007. godine (L∞ = 15,36, K = 0,98 i t0 = -0,399 ). Izračunat je indeks uspješnosti rasta (φ’), i srednja vrijednost ovog indeksa na osnovu svih izračunatih parametara rasta iznosi 2,416. Izračunate trenutne stope smrtnosti za populaciju inćuna u obije godine bile su slične (u prvoj istraživanoj godini Z = 6,65, u drugoj Z = 5,99), i njihove vrijednosti pokazuju visok stepen ukupne smrtnosti populacije inćuna na području Kotorskog zaliva. Izračunata je i stopa prirodnog mortaliteta (M = 5,95), kao i ribolovni mortalitet (F = 0,7). Povećanje veličine oka sa 6 mm u 2004-2005. godini na 8 mm u 2006 - 2007. godini dovelo je i do povećanja L50% sa 7,359 cm na 8,47cm, kao i t50% sa 0,285 na 0,421 godina, čime je omogućeno većem broju jedinki da dostignu polnu zrelost. Analizom reproduktivnih karakteristika inćuna putem ispitivanja GSI i histologije gonada, utvrđeno je da reproduktivni ciklus ove vrste na području Kotorskog zaliva traje od aprila do oktobra mjeseca. Ženke su brojnije u odnosu na mužjake i odnos polova je 0,92. Mikroskoskom analizom jajnika inćuna utvrđena je najmanja dužina dostizanja polne zrelosti za ženke koja iznosi 7,5 cm i to je za sada najmanja mikroskopski potvrđena dužina na Jadranu. Procijenjena je i biomasa inćuna (B = 433.2 t), koeficijent ranjivosti q = 0,006371, kao i stopa eksploatacije E = 0,106. Na osnovu ovih podataka izračunat je optimalni ribolovni napor (fopt) za ovo područje i on iznosi 78 potezanja mreže u toku jednog mjeseca, što znači da bi broj izdatih dozvola za ovaj tip ribolova trebalo da bude 8 do 9 dozvola godišnje. This thesis presents the results of a two-year research of ecological parameters of juvenile European anchovy, Engraulis encrasicolus (L.), in the Bay of Kotor. Considering that the anchovy fisheries in this region have been for centuries performed using beach seines with very small mesh size (6 mm), one of the main goals of the thesis was to determine whether this type of fisheries can be allowed to continue, and to what extent, in order to preserve the anchovy population in the Bay of Kotor. Samples were collected from commercial beach seine catches in periods from June 2004 to July 2005, and from July 2006 to June 2007. A total of 4203 specimens were studied. Anchovy made up 37% of the total catch in both sampling periods, while the catch per unit effort (CPUE) was estimated to be 150 kg per haul. The length frequency of the studied sample ranged from 5.2 to 13.2 cm total length (TL), with an average length of 8.6 cm TL. The power coefficient of length–weight relationship was estimated to be b = 3.122, while the relative condition factor ranged from 0.981 to 1.017, with an average value of 1.003±0.009. This is the first time that the otoliths of juvenile anchovy were analysed, not only in the area, but in the southern Adriatic Sea in general. Age in days was determined, and, based on the results obtained from otolith readings, growth parameters (L∞ = 10.41 cm, K= 3.36, t0 = −0.074) were estimated, as well as the length at which larvae metamorphose to the juvenile stage (32.41 mm), and the daily growth rate of the juvenile anchovy (0.41 mm/day). Otolith growth rate and their asymptotic length (L∞ = 1918 μm) were also estimated, and the maximum otolith growth rate was 62 days after hatching. Estimated growth parameters for juveniles using modal progression were L∞ = 9.21 cm, K= 4.51, t0 = −0.04 for the period 2004-2005, and L∞ = 10.94 cm, K= 2.25, t0 = −0.175 for the period 2006-2007. The same method was used to estimate growth parameters for the entire anchovy population for 2004-2005 (L∞ = 15.41 cm, K= 0.59, t0 = −0.761) and 2006-2007 (L∞ = 15.36 cm, K= 0.98, t0 = −0.399). Growth VII performance index (φ’) was also estimated, and its mean value based on all growth parameters was φ’ = 2.416. Instantaneous mortality rate were similar in both study periods (Z = 6.65 in 2004-2005, and Z = 5.99 in 2006-2007), and they indicate a high level of the total mortality within the Bay of Kotor. Natural mortality was estimated to be M = 5.95, and fishing mortality was F = 0.7. The increase in mesh size from 6 mm in 2004-2005 to 8 mm in 2006-2007 lead to an increase of L50% from 7.359 cm to 8.47 cm, and of t50% from 0.285 to 0.421 years, which allowed a greater number of individuals to reach sexual maturity. The analysis of reproductive characteristics using the gonadosomatic index (GSI) and gonad histology showed that the reproductive cycle of this species in the Bay of Kotor lasts from April to October. Females were more numerous compared to males, and the sex ratio was estimated to be 0.92. Microscopic analysis of female ovaries was used to estimate the minimum length at first maturity, which occurs at 7.5 cm. This is the smallest microscopically confirmed length at first maturity for the anchovy in the Adriatic Sea. Biomass of anchovy was estimated at B = 433.2 t, the coefficient of vulnerability at q = 0.006371), and the exploitation rate at E = 0.106. Based on this data, the optimum fishing rate (fopt) for the area was estimated at 78 hauls per month. This implies that a number of licences for this type of fisheries should be limited to 8 or 9 licences pr year. Univerzitet u Beogradu Biološki fakultet Krpo-Ćetković, Jasmina Krpo-Ćetković, Jasmina Regner, Slobodan Hegediš, Aleksandar Joksimović, Aleksandar 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=22 https://fedorabg.bg.ac.rs/fedora/get/o:2262/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024496050 sr Autorstvo-Nekomercijalno 3.0 Srbija (CC BY-NC 3.0)

oai:eteze.bg.ac.rs:23 2013-09-25T00:00:00Z 1

Uticaj ishrane obogaćene ugljenim hidratima na morfološke i ultrastrukturne odlike pankreasa pacova u uslovima eksperimentalno indukovanog hipotireoidizma The effect of carbohydrate rich diet on rat pancreas morphological and ultrastructural characteristics in experimentally induced hypothyroidism Ukropina, Mirela, 1975- Pankreas, hipotireoidizam, saharoza, acinusne ćelije, β-ćelije, svetlosna mikroskopija, imunohistohemija, elektronska mikroskopija, stereologija Pancreas, hypothyroidism, sucrose, acinar cells, β-cells, light microscopy, immunohistochemistry, electron microscopy, stereology Datum odbrane: 09.07.2012. Pankreas je žlezda sa egzokrinom i endokrinom funkcijom. Proizvodi njegove egzokrine komponente od vitalnog su značaja za proces varenja hrane. Endokrine ćelije pankreasa grupisane u Langerhansova ostrvca proizvode insulin i glukagon, hormone koji regulišu metabolizam pre svega ugljenih hidrata i neophodni su za održavanje optimalne koncentracije glukoze u krvi. Sekretna aktivnost pankreasa, naročito njegove endokrine komponente, pod kontrolom je kompleksnih endokrinih, parakrinih i neuralnih mehanizama. Hormoni tireoidne žlezde ključni su regulatori bazalnog metabolizma, rasta i razvića. Potrebni su za normalno funkcionisanje gotovo svih organa i organskih sistema, a njihov značaj u metabolizmu ugljenih hidrata poznat je već decenijama. Funkcije endokrinog pankreasa i tireoidne žlezde, kao i efekti koje ostvaruju njihovi hormoni, uzajamno su povezani i međusobno zavisni. U kliničkoj praksi relativno je česta koegzistencija disfunkcije tireoidne žlezde i razvoj insulinske rezistencije, koja je predvorje nastanka dijabetesa tipa 2. Ishrana bogata prostim šećerima, uz smanjen nivo fizičke aktivnosti karakteristika je savremenog načina života, naročito u industrijski razvijenijim zemljama sveta. Pri kontinuiranom unosu ugljenih hidrata pankreas radi pod povećanim opterećenjem, intenzivno proizvodeći insulin, što dugoročno gledano može dovesti do patofizioloških procesa na nivou unutarćelijskih organela i eventualno do gubitka β- ćelija, odnosno do dijabetesa tipa 2. Osnovni cilj ove teze bio je da se detaljnom analizom stekne uvid u morfofunkcionalne karakteristike pankreasa pacova pod uticajem ishrane obogaćene saharozom, u uslovima sistemskog hipotireoidizma indukovanog metimazolom. U tronedeljnom eksperimentu korišćeni su mužjaci albino pacova Wistar soja, držani pod standardnim laboratorijskim uslovima. Životinje su u odnosu na ponuđeni rastvor u vodi za piće podeljene u četiri grupe. Kontrolna grupa životinja pila je čistu česmensku vodu, hipotireoidizam je indukovan 0.02% rastvorom metimazola, dok je pankreas funkcionalno opterećen unosom 10% rastvora saharoze. Pacovi poslednje grupe pili su kombinovani rastvor metimazola i saharoze, već pomenutih koncentracija. Pankreas je na uobičajen način pripremljen za morfološku i stereološku analizu na nivou svetlosne i elektronske mikroskopije. Pored rutinskih metoda bojenja hematoksilinom i eozinom, toluidin plavim i AZAN-om, korišćene su metode imunohistohemije za detekciju insulina, glukagona, somatostatina, pankreasnog polipeptida, PDX1, α-SMA i Ki67 proteina, kao i specifično bojenje propidijum jodidom. Dobijeni rezultati pokazali su sledeće: - Tronedeljni tretman metimazolom doveo je do uspostavljanja umerenog sistemskog hipotireoidizma, nezavisno od režima ishrane. Nivoi tireoidnih hormona u cirkulaciji bili su smanjeni, a životinje su zaostajale u rastu... The pancreas is a gland with both exocrine and endocrine function. The products of its exocrine component are vital to the food digestion. Its endocrine function is based on secretory action of several types of endocrine cells that cluster together to form islets of Langerhans. Some of them produce insulin and glucagon, hormones that regulate primarily carbohydrate metabolism and are essential for maintaining optimal blood glucose concentrations. Secretory action of the pancreas, especially its endocrine component, is controlled by a complex endocrine, paracrine and neural mechanisms. Thyroid hormones are key regulators of the basal metabolism, growth and development. They are necessary for normal function of almost all organs and organ systems; their importance in the metabolism of carbohydrates has been known for decades. The functions of the endocrine pancreas and thyroid gland, and effects of their hormones are mutually connected and interdependent. In clinical practice the coexistence of thyroid dysfunction and the development of insulin resistance, which is a good prognostic factor for type 2 diabetes occurrence, is relatively frequent. A diet rich in simple sugars, along with reduced physical activity is a feature of modern lifestyle in developed countries of the world. Continuous intake of carbohydrates represents a form of stress in which pancreas intensively produces insulin, which in the long term can lead to pathophysiological processes at the level of intracellular organelles, and eventually to loss of β-cells, i.e. to type 2 diabetes. The aim of this work was to gain an insight into the detailed morpho-functional characteristics of the rat pancreas under the influence of sucrose rich diet, in terms of systemic hypothyroidism induced by methimazole. The obtained results show that: - Moderate systemic hypothyroidism was established after three-week methimazole treatment, regardless of the diet. Levels of thyroid hormones in the circulation were reduced, and the animals fell behind in growth... Univerzitet u Beogradu Biološki fakultet Čakić-Milošević, Maja Koko, Vesna Glišić, Radmila 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=23 https://fedorabg.bg.ac.rs/fedora/get/o:2268/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024495026 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:24 2013-09-25T00:00:00Z 1

Odgovor hipotalamo-hipofiznog sistema pacova na izoflavone soje : morfofunkcionalna studija Effects of soy isoflavones on the hypothalamic-pituitary system in rats: a morphofunctional study Trifunović, Svetlana L., 1975- Genistein, daidzein, GHRH, SS, GH ćelije, CRH, ACTH ćelije Genistein, daidzein, GHRH, SS, GH cells, CRH, ACTH cells Datum odbrane: 10.07.2012. Izoflavoni soje, genistein i daidzein, se sve više koriste u preventivi i alternativnoj terapiji različitih patoloških stanja. Uticaj izoflavona soje na neuroendokrini sistem bio je, a i danas je, predmet istraživanja različitih studija. Veliki broj literaturnih podataka govori o uticaju izoflavona soje na reproduktivni sistem, s obzirom na njihovu estogensku i anti-estrogensku aktivnost. Ipak, podaci o njihovom uticaju na somatotropni i adrenokortikotropni sistem oskudni su, a neophodni, imajuću u vidu značaj ovih sistema za normalan razvoj i funkcionisanje organizma. Takoñe, mnogobrojne in vitro studije obezbeñuju samo limitirane informacije o potencijalnim efektima in vivo. Cilj ove studije je bio da se ispita uticaj hroničnih tretmana estradioldiproprionatom, genisteinom i daidzeinom na histološke, stereološke i biohemijske parametre somatotropnog i adrenokortikotropnog sistema orhidektomisanih adultnih pacova. Na početku eksperimenta adultni pacovi Wistar soja, stari 3 meseca, su podeljeni u dve eksperimentalne grupe: lažno orhidektomisanu (Sham) i orhidektomisanu (Orx) grupu. Dve nedelje nakon sham operacije ili orhidektomije pacovi su podeljeni u sedam eksperimentalnih grupa. Prvu (Sham1) grupu su sačinjavale sham operisane životinje subkutano (s.c.) tretirane odgovarajućom zapreminom sterilnog maslinovog ulja, medijumom estradiol-diproprionata (medijum I). Drugu (Orx1) grupu su sačinjavale orhidektomisane životinje s.c. tretirane odgovarajućom zapreminom medijuma I. U trećoj (Orx1+E) grupi orhidektomisane životinje su s.c. tretirane estradioldipropionatom u medijumu I (0,6 mg/kg t.m.). Četvrta (sham operisana - Sham2) i peta (orhidektomisana - Orx2) grupa s.c. su tretirane odgovarajućom zapreminom mešavine alkohola i sterilnog maslinovog ulja, medijumom genisteina i daidzeina (u odnosu 1:2; medijum II). Šestu (Orx2+G) grupu su sačinjavale orhidektomisane životinje s.c. tretirane genisteinom u medijumu II (30 mg/kg t.m.), dok je sedma (Orx2+D) grupa orhidektomisanih pacova s.c. tretirana daidzeinom u istom medijumu (30 mg/kg t.m.). Sve grupe životinja su dobijale tretman tokom tri nedelje (hroničan tretman), a žrtvovane su 24 h nakon poslednje primljene doze. Pre početka i nakon završenog tretmana izmerene su telesne mase životinja svih eksperimentalnih grupa, dok su mase hipofiza izmerene nakon žrtvovanja. Za lokalizaciju arkuatnog (Arc) i periventrikularnog (Pe) jedra, paravenrikularnog jedra (PVN) i eminencije medijane (ME) korišćeno je histološko bojenje krezil-ljubičastom bojom. Za obeležavanje oslobañajućih hormona hipotalamusa (oslobañajućeg hormona hormona rasta–GHRH, somatostatina-SS, kortikotropnog oslobañajućeg hormona-CRH) i ćelija adenohipofize (somatotropnih–GH i adrenokortikotropnih-ACTH) korišćeno je imunohistohemijsko bojenje. Histološki i imunohistohemijski obojeni preseci hipotalamusa, kao i imunohistohemijski obojeni preseci hipofiza stereološki su analizirani, uz pomoć newCAST stereološkog softverskog paketa. Dobijene su vrednosti: volumena Arc i Pe jedra i PVN, volumenske gustine SS neurona, volumena hipofize, volumenske i numeričke gustine GH i ACTH ćelija, apsolutnog broja i volumena GH i ACTH ćelija. Koncentracija GH i ACTH u cirkulaciji odreñena je biohemijskim metodama. Dobijeni podaci su statistički obrañeni... The soy isoflavones genistein and daidzein are being used increasingly as preventive or alternative therapeutics in various pathological conditions. The effects of soy isoflavones on the neuroendocrine system were, and still are, the subject of numerous studies. Literature data predominantly focus on their effects on the gonadotrophic axis, considering the soy isoflavones established estrogenic and antiestrogenic mode of action. However, data about their potential effects on the somatotrophic and adrenocorticotrophic systems are rather scarce, but nevertheless very meaningful, considering the importance of these systems for the normal development and function of an organism. Furthermore, in vitro studies provide only limited data, that cannot be fully extrapolated to in vivo conditions. The aim of this study was to investigate the effects of chronically applied estradiol dipropionate, genistein and daidzein on the histological, stereological and biochemical parameters of somatotrophic and adrenocorticotrophic systems in orchidectomized adult rats. Initially, adult (three months old) Wistar rats were divided into two groups: sham operated (Sham) and orchidectomized (Orx). Two weeks after the surgery, the rats were subdivided into seven experimental groups. The first group (Sham1) included sham operated rats subcutaneously (s.c.) treated with an adequate volume of sterile olive oil, the medium for estradiol dipropionate (medium I). In the second group (Orx1) were orchidectomized rats s.c. treated with an adequate volume of medium I. The third group (Orx1+E) was comprised of orchidectomized rats s.c. treated with estradiol dipropionate in medium I (0.6 mg/kg b.w.). The fourth (sham operated – Sham2) and fifth (orchidectomized – Orx2) group of rats were s.c. treated with adequate volumes of absolute ethanol and sterile olive oil mixture, the medium for genistein or daidzein (mixing ratio was 1:2; medium II). In the sixth group (Orx2+G) were orchidectomized rats s.c. treated with genistein in medium II (30 mg/kg b.w.), while the seventh group (Orx2+D) included orchidectomized rats s.c. treated with daidzein in the same medium (30 mg/kg b.w.). All the groups of animals received the treatment during three weeks (chronic treatment), and were sacrificed 24 h after the last injected dose. All the animals were weighed before and after the treatment, while the pituitary weights were measured after sacrificing. For the localization of arcuate (Arc), periventricular (Pe) and paraventricular (PVN) nuclei, as well as for median eminence (ME) cresyl violet histochemical staining was used. Hypothalamic releasing hormones (growth hormone releasing hormone – GHRH, somatostatin – SS, corticotrophin releasing hormone – CRH) and pituitary cells (somatotrophic – GH and adrenocorticotrophic – ACTH) were immunohistochemically (peroxidase-antiperoxidase) labeled. Histochemically stained and immunohistochemically labeled hypothalamic sections, as well as immunohistochemically labeled pituitary sections were stereologically analysed, using newCast stereological software package. The following values were obtained: the Arc, Pe and PVN nuclei volumes, volume density of SS neurones, volumes of the pituitaries, the volume and numerical density of GH and ACTH cells, as well as the absolute numbers and volumes of GH and ACTH cells. The circulating GH and ACTH were determined biochemically. The obtained data were statistically processed... Univerzitet u Beogradu Biološki fakultet Koko, Vesna Manojlović-Stojanoski, Milica Milošević, Verica Šošić-Jurjević, Branka Ajdžanović, Vladimir 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=24 https://fedorabg.bg.ac.rs/fedora/get/o:2269/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024496818 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:25 2013-09-25T00:00:00Z 1

Uloga angiotenzina II i reaktivnih vrsta kiseonika tokom razvoja akutne bubrežne insuficijencije u eksperimentalnoj hipertenziji The role of angiotensin II and reactive oxygen species during the acute renal failure development in experimental hypertension Ivanov, Milan S., 1983- Akutna bubrežna insuficijencija; Hipertenzija; Renin angiotenzin aldosteron sistem; Angiotenzin II; Reaktivne vrste kiseonika; Losartan; Tempol; Pacovi sa urodjenom hipertenzijom Acute renal failure; Hypertension; Renin angiotensin aldosterone system; Angiotensin II; Reactive oxygen species; Losartan; Tempol; Spontaneously hypertensive rat (SHR) Datum odbrane: 28.07.2012. Akutna bubrežna insuficijencija (ABI) se definiše kao nagli gubitak bubrežne funkcije. Uzroci nastanka ABI su mnogobrojni, a mehanizmi razvoja još uvek nedovoljno jasni. Karakterišu je iznenadna pojava, brzi tok, neizvesna i često loša prognoza krajnjeg ishoda bolesti. ABI je česta pojava kod hospitalizovanih pacijenata, a učestalost njenog nastanka na odeljenjima intenzivne nege se kreće do 30%. Udružena sa drugim oboljenjima, poput hipertenzije, uzrokuje visok stepen mortaliteta. Savremena istraživanja pokazuju da hipertenzija i oksidativni stres imaju važnu ulogu u progresiji bubrežnih oboljenja, što je usmerilo i stavilo akcenat naših istraživanja na uloge ova dva patogenetska faktora u nastanku i progresiji ABI. Sistem renin angiotenzin aldosteron (RAAS) ima značajnu ulogu u održanju krvnog pritiska i homeostatskih mehanizama bubrega. On u velikoj meri reguliše bubrežnu hemodinamiku i vaskularnu reaktivnost, a kako je intrarenalna vazokonstrikcija jedan od glavnih mehanizama razvoja ABI, očita je njegova uloga u patogenetskim mehanizmima nastanka ove bolesti. Oksidativni stres predstavlja disbalans između produkcije reaktivnih vrsta kiseonika (RVK) i sposobnosti biološkog sistema da ih uklanja ili da reparira oštećenja nastala produkcijom ovih molekula. Reaktivne vrste kiseonika su izuzetno reaktivne supstance usled postojanja nesparenih elektrona, i kao takve mogu da uzrokuju oštećenja na DNK, RNK, kao i nekim proteinima koji imaju ulogu u procesu starenja. Pokazano je da oksidativni stres ima veliku ulogu u razvoju mnogih oboljenja, kao što su Alchajmerova i Parkinsonova bolest, i neki kardiovaskularni poremećaji. Takodje je dokazano da, prilikom ishemičnih povreda organa i tkiva, nakon hipoksije, a tokom reperfuzije, dolazi do povećane produkcije molekula RVK. Iz pomenutih razloga, sasvim je izvesno da u ishemičnoj formi ABI povećana koncentracija ovih molekula, doprinosi nastanku i razvoju ovog teškog oboljenja... Acute renal failure (ARF) is defined as a sudden loss of renal function. It’s multifactorially caused, but the mechanism of pathogenesis and developement of this disease is still uncomplitely defined. ARF is characterized by sudden appearance, rapid progression of disease and very uncertain and often fatal outcome. ARF frequently occurres with hospitalized patients. The frequency of its occurrence in the intensive care units moves up to 30%. Associated with other diseases, such as hypertension, it causes high rate mortality. Recent studies show that hypertension and oxidative stress have an important role in the renal disease progression. This fact directed the focus of our study towards the influence of these two pathogenetic factors in development and progression of ARF. The system rennin angiotensin aldosterone (RAAS) has a great role in blood pressure control and kidney homeostatic mechanisms. It mostly regulates the renal hemodynamic, but considering the fact that the intrarenal vasoconstriction is one of the major mechanisms of ARF development, it obviously influences the pathogenetic mechanisms in the development of this disorders. Oxidative stress is defined as a disbalance between the production of reactive oxygen species (ROS) and an ability of biological system to remove or fix the damage made due to production of these molecules. Reactive oxygen species are highly reactive due to presence of unpaired electrons and consequently lead to damage of DNA, RNA and some other ageing related proteins. There is evidence that the oxidative stress has a great influence in the progression of numerous diseases, such as Alzheimer’s, Parkinson’s, as well as some cardiovascular disorders. Furthermore, during the ischemia/reperfusion injuries of organs and tissues, there is increased reactive oxygen species molecule production. Thus, the ischemic type of ARF is characterized by a high concentration of these molecules which contribute to the development of this devastating illnes... Univerzitet u Beogradu Biološki fakultet Miloradović, Zoran Đorđević, Jelena Mihailović-Stanojević, Nevena 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=25 https://fedorabg.bg.ac.rs/fedora/get/o:2270/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41537039 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:26 2013-09-25T00:00:00Z 1

Transkripciona regulacija razvoja i hiperplazije mrkog masnog tkiva Transcriptional regulation of brown adipose tissue hiperplasia and development Veličković, Ksenija D. 1977- Mrko masno tkivo, hiperplazija, hladnoća, transkripcioni faktori, adipogeneza, angiogeneza Brown adipose tissue, hyperplasia, cold, transcription factors, adipogenesis, angiogenesis Datum odbrane: 22.08.2012. Univerzitet u Beogradu Biološki fakultet Korać, Aleksandra Čvoro, Aleksandra Korać, Bato Srdić, Biljana 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=26 https://fedorabg.bg.ac.rs/fedora/get/o:2271/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024497074 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:27 2013-09-25T00:00:00Z 1

Uticaj starenja i dugotrajne dijetalne restrikcije na metabolizam holesterola u prednjem mozgu pacova Effects of aging and long-term dietary restrictions on cholesterol metabolism in the rat forebrain Smiljanić, Kosara, 1978- Starenje, dijetalna restrikcija, korteks, hipokampus, pacov, holesterol Ageing, dietary restriction, cortex, hippocampus, rat, cholesterol Datum odbrane: 09.07.2012. Starenje centralnog nervnog sistema (CNS) praćeno je brojnim promenama koje dovode do narušavanja nervnih funkcija, pre svega kontrole motorike i kognitivnih sposobnosti. Smatra se da su kognitivni poremećaji tokom starenja posledica smanjene sinaptičke plastičnosti, naročito u korteksu i hipokampusu, regionima mozga izuzetno važnim za procese učenja i pamćenja. Najvažniji faktor sredine kojim se može uticati na starenje uopšte, a samim tim i na starenje mozga je režim redukovane ishrane, bez pothranjenosti. Pored toga što se već nekoliko decenija zna da redukovana ishrana produžava životni vek mnogih vrsta, uključujući i sisare, pokazano je da ona odlaže i ublažava starosno zavisne promene u nervnom sistemu. Holesterol je najzastupljeniji lipid u ćelijama sisara. Učestvujući u izgradnji fosfolipidnog dvosloja bioloških mambrana, on reguliše njihovu fluidnost, propustljivost i rigidnost, a samim tim i funkcionalna svojstva membranskih proteina, poput jonskih kanala i transmiterskih receptora. Metabolizam holesterola predstavlja važan aspekt sinaptičke plastičnosti, jer je pokazano da je holesterol neophodan za biogenezu i transport sinaptičkih vezikula, kao i za prvilnu funkcionalnu organizaciju lipidnih ostvaca. Od svih organa u telu, mozak sadrži najviše holesterola. Održavanje homeostaze holesterola neophodno je za normalno i neometano funkcionisanje CNS... Ageing of the central nervous system is associated with a number of changes that disturb nerve function, especially motor control and cognitive abilities. It is believed that cognitive disorders in aging are consequence of reduced synaptic plasticity, especially in the cortex and hippocampus, brain regions extremely important for learning and memory processes. Dominant factor that can influence aging in general, and therefore the aging of the brain is reduced diet regime, without malnutrition. In addition to being known for decades that reduced caloric intake prolongs life span of many species, including mammals, it is shown that it delays and alleviates age-dependent changes. Cholesterol is the most abundant lipid in mammalian cells. By participating in the construction of phospholipid bilayer of biological membranes, it regulates their fluidity, permeability and rigidity, and consequently the functional properties of membrane proteins, such as ion channels and transmmitters receptors. Cholesterol metabolism represents one aspect of synaptic plasticity, as has been shown that cholesterol is essential for biogenesis of synaptic vesicles, and vesicle transport, as well as for proper functional organization of lipid rafts. The brain contains the most cholesterol of all the organs in the body. Maintenance of cholesterol homeostasis is essential for proper functioning of the central nervous system... Univerzitet u Beogradu Biološki fakultet Kanazir, Selma Korać, Bato Mladenović-Đorđević, Aleksandra Ruždijić, Sabera Rakić, Ljubisav 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=27 https://fedorabg.bg.ac.rs/fedora/get/o:2272/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41541647 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:28 2013-09-25T00:00:00Z 1

Karakterizacija površinskih molekula bakterijskih ćelija odgovornih za potencijalnu probiotičku aktivnost prirodnih izolata laktobacila Characterization of surface molecules from bacterial cells involved in the potential probiotic activity of natural lactobacilli isolates Nikolić, Milica J., 1980- Lactobacillus, probiotik, agregacija, egzopolisaharid (EPS), interakcije bakterija sa ćelijama u kulturi, limfociti, plazmid, operon Lactobacillus, probiotic, aggregation, exopolysaccharide (EPS), interaction of bacteria with cell cultures, lymphocytes, plasmid, operon Datum odbrane: 07.05.2012. Probiotički potencijal bakterija u velikoj meri zavisi od površinskih karakteristika bakterijske ćelije. Stoga su u ovom radu analizirane površinske komponente ćelija odgovorne za agregacione sposobnosti i produkciju egzopolisaharida (EPS) prirodnih izolata laktobacila. Sojevi laktobacila korišćeni u ovom radu su izolovani iz autohtonih sireva proizvedenih u domaćinstvima prema tradicionalnoj tehnologiji. Odabrani laktobacili koji su ispoljavali autoagregaciju (BGAR75, BGGR2-68, BGGR2-82, BGDP9-85, BGDP1-84, BGNJ1-3, BGNJ1-61, BGNJ1-70), kao i dva odabrana soja koja ne agregiraju (BGAR76 i BGGR2-20), su klasifikovani na osnovu poređenja nukleotidnih sekvenci gena za 16S rRNK sa NCBI bazom podataka i svrstani u grupu Lactobacillus casei. Soj BGDU4-71 je determinisan sekvenciranjem 16S rDNK kao Lactobacillus delbrueckii subsp. bulgaricus, a soj BGCG11, proizvođač egzopolisaharida (EPS-CG11), je determinisan AFLP metodom kao Lactobacillus paraplantarum. U cilju karakterizacije faktora uključenih u proces agregacije u ovom radu su analizirani brzina i tip autoagregacije. Brzina autoagregacije (utvrđivana spektrofotometrijski) kao i oblik agregata su varirali kod sojeva. Najbrže su agregirali i formirali najkrupnije agregate sojevi BGSJ2- 8, BGDP1-84 i BGNJ1-6. Karakterizacija prirode faktora koji utiču na sposobnost autoagregacije izabranih sojeva laktobacila je rađena intenzivnim pranjem sojeva koji agregiraju u bidestilovanoj vodi i u PBS rastvoru. Uočeno je da se autoagregacija gubila intenzivnim pranjem u bidestilovanoj vodi kod svih sojeva, osim kod BGDP1-84, na osnovu čega je zaključeno da je prisustvo jona neophodno za formiranje agregata. Osim toga, pokazano je da su neki od faktora autoagregacije proteinske prirode s obzirom da se ova karakteristika gubila nakon tretmana proteinazom K. Lb. paracasei subsp. paracasei BGSJ2-8 je formirao koagregate sa Listeria innocua ATCC33090, Escherichia coli ATCC25922 ili sa Salmonella enterica ser. Typhimurium TR251, dok njegov derivat BGSJ2-81 koji je izgubio sposobnost autoagregacije nije koagregirao... The probiotic potential of bacteria depends on the surface characteristics of bacterial cells. Keeping this in mind, in this work the surface components of the cells responsible for the aggregation ability and the production of exopolysaccharides (EPS) were analyzed from the natural isolates of lactobacilli. Lactobacilli strains used in this work were isolated from autochthonous cheeses produced in households according to the traditional technology. Selected lactobacilli showing the autoaggregation ability (BGAR75, BGGR2-68, BGGR2- 82, BGDP9-85, BGDP1-84, BGNJ1-3, BGNJ1-61, BGNJ1-70) as well as two selected strains which do not form aggregates (BGAR76 and BGGR2-20) according to the comparison of their 16S rRNA gene sequence to the NCBI database were classified in the group Lactobacillus casei. The strain BGDU4-71 using the 16S rRNA gene sequence was determined as Lactobacillus delbrueckii subsp. bulgaricus and the strain BGCG11, the producer of the exopolysaccharide (EPS-CG11), was determined by AFLP methodology as Lactobacillus paraplantarum. In order to characterize factors involved in the aggregation process the kinetics and the type of autoaggregation were analyzed. The kinetics (spectrofotometrically determined) as well as the shape of the aggregates was variable among the strains. Strains with fastest and the largest aggregates were BGSJ2-8, BGDP1- 84 and BGNJ1-6. The characterization of the nature of factors involved in autoaggregation of selected strains of lactobacilli was performed by exhaustive washing of the strains in distilled water and in PBS solution. It was noticed that the autoaggregation ability was lost after exhaustive washing in distilled water in all tested strains except BGDP1-84, which led to the conclusion that the presence of some ions was necessary for the formation of the aggregates. Besides, it was shown that some of the factors promoting autoaggregation were of proteinaceous nature, since the ability was lost after the proteinase K treatment. Lb. paracasei subsp. paracasei BGSJ2-8 was able to form coaggregates with Listeria innocua ATCC33090, Escherichia coli ATCC25922 or with Salmonella enterica ser. Typhimurium TR251, while its derivative BGSJ2-81 that was not able to autoaggregate, did not show coaggregation... Univerzitet u Beogradu Biološki fakultet Golić, Nataša Jovčić, Branko Kojić, Milan 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=28 https://fedorabg.bg.ac.rs/fedora/get/o:2276/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/40744207 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:29 2013-09-25T00:00:00Z 1

Uticaj purinskih nukleozidnih analoga, ribavirina i tiazofurina, na aktivaciju mikroglije u uslovima inflamacije The effect of purine nucleoside, analogues, ribavirin and tiazofurin, on microglial activation under inflammatory conditions Savić, Danijela, 1976- Centralni nervni sistem, inflamacija, mikroglija, eksperimentalni autoimunski encefalomijelitis, ćelijska kultura Central nervous system, inflammation, microglia, experimental autoimmune encephalomyelitis, cell culture Datum odbrane: 01.10.2012. Aktivacija mikroglije jedno je od glavnih obeležja eksperimentalnog autoimunskog encefalomijelitisa (EAE) i drugih neuroloških poremećaja koje odlikuje hronična inflamacija. Cilj ove studije bio je da se proceni sposobnost dva analoga purinskih nukleozida, ribavirina (RBV) i tiazofurina (TR), da modulišu inflamatorni odgovor aktivirane mikroglije, in vivo i in vitro. U in vivo studiji, koja je izvedena na EAE modelu indukovanom ubrzgavanjem encefalitogene emulzije u šapu Dark Agouti pacova, pokazano je da tretman životinja kombinacijom oba analoga, počev od pojave prvih simptoma pa tokom sledećih 15 dana, dovodi do smanjenja težine bolesti, a na histološkom planu do smanjenja broja i stepena aktivacije mikroglije. Budući da kombinovani tretman RBV i TR dovodi do supresije simptoma EAE i do redukcije reaktivne mikroglioze, formulisana je hipoteza da ovaj tretman, pored ranije opisanih sistemskih efekata u imunskom i vaskularnom sistemu, ostvaruju centralni efekat i to delujući prvenstveno na ćelije mikroglije. Uticaj RBV i TR, kao i kombinovane primene oba analoga detaljnije je ispitan u primarnoj kulturi mikroglijskih ćelija. Aktivacija mikroglije, indukovana lipopolisaharidom bakterijskog zida gram negativnih bakterija, (LPS), izazvala je tipičan odgovor reaktivne mikroglioze. Antiinflamatorni potencijal RBV, TR i RBV+TR ispitan je u pogledu citotoksičnosti, indukcije morfoloških promena, produkcije azot monoksida (NO), oslobađanja proinflamatornih citokina i nuklearne translokacije NF-κB. Ispitan je citototoksični potencijal RBV (1 – 20 μM), TR (1 – 20 μM) i kombinovanog tretmana (10 μM RBV + 5 μM TR) i određene su EC50 doze pri kojima se postiže polovina maksimalnog citotoksičnog efekta. RBV, TR i kombinovani tretman smanjuju ukupnu produkciju NO u kulturi stimulisanoj LPS-om, a taj efekat se pripisuje smanjenju ukupnog broja ćelija u kulturi. RBV, TR i RBV+TR menjaju ameboidnu morfologiju aktivirane mikroglije, tako što smanjuju prosečnu površinu ćelija u kulturi. Tretman RBV, TR i RBV+TR smanjuju translokaciju NF-κB/p65 u jedro. Primenjeni tretmani smanjuju ukupno oslobađanje TNF-α i IL-6, što je verovatno posledica smanjenja ukupnog broja aktiviranih ćelija, a RBV i kombinovani tretman povećavaju ekspresiju IL-1β. U primarnoj kulturi mikroglijskih ćelija potvrđena je genska i proteinska ekspresija uravnotežujućih nukleozidnih transportera 1 i 2 (ENT1, 2), koji učestvuju u transportu RBV i TR u ćelije. Ukupno gledano, rezultati dobijeni ovom studijom ukazuju da RBV i TR, pojedinačno ili u kombinaciji, deluju citotoksično na aktiviranu mikrogliju i menjaju njenu morfologiju, a ispoljavaju i imunomodulatorno dejstvo tako što snižavaju produkciju NO, smanjuju signalizaciju posredovanu NF-κB/p65 i redukuju produkciju proinflamatornih citokina. Activation of microglia is the hallmark of experimental autoimmune encephalomyelitis (EAE) and other neurodegenerative disorders associated with chronic neuroinflammation. The present study addressed the potency of purine nucleoside analogues ribavirin (RBV) and tiazofurin (TR) to modulate the microglial inflammatory response in vivo and in vitro. In this study, we induced animal model of multiple sclerosis – experimental autoimmune encephalomyelitis (EAE) by subcutaneous injection of encephalitogenic emulsion in the hind paw of Dark Agouti rats and showed that therapeutic treatment of EAE animals with combination of these two nucleoside analogues reduced disease severity. In addition, histological analysis indicated that RBV and TR also decreased the number and activation status of microglial cells. Since the combined treatment with RBV and TR leads to suppression of EAE symptoms and reduction of reactive microgliosis, we proposed hypothesis that this treatment, in addition to previously described effects in immune and vascular system, may act in central nervous system targeting primarily microglial cells. Therefore, in further experiments we examined effect of RBV, TR and their combination (RBV+TR) on primary microglial cell culture. Activation of microglial cells with bacterial lipopolysaccharide (LPS) triggers typical microglial responses to inflammation. Anti-inflammatory potential of RBV, TR and RBV+TR was tested in terms of influencing microglial morphological changes, NO production, nuclear factor-κB translocation and proinflammatory cytokines release, after LPS stimulation. The cytotoxic effects of RBV (1 – 20 μM), TR (1 – 20 μM) and their combination (10 μM RBV + 5 μM TR) are determined, as well as the dosages that achieved half-maximal inhibitory effect (EC50). RBV, TR and combination treatment lowered NO levels in LPS stimulated cultures as a result of decreased cell number. RBV, TR and RBV+TR induced shrinkage of average cell surface of LPS activated amoeboid microglial cells. Treatment with RBV, TR and RBV+TR of activated microglia strongly reduced the nuclear translocation of NF-κB/p65 and suppressed proinflammatory immune response genes. Applied treatments also exerted suppression of TNF-α and IL-6 release in activated microglia manly by reduction of cell number. At the same time, RBV and RBV + TR treatment additionally increased LPS-induced IL-1β gene expression and release. In primary microglial cell culture, gained results confirmed gene and protein expression of equilibrative nucleoside transporters (ENTs), proteins that are responsible for the putative entry of RBV and TR into cells. Results obtained in this study indicate that RBV and TR, alone or in a combination, attenuate neuroinflammatory response, probably by exerting cytotoxicity on activated microglial cells, reduction of NO levels, attenuation NF-κB signaling and decrease of proinflammatory cytokine release. Univerzitet u Beogradu Biološki fakultet Peković, Sanja Nedeljković, Nadežda Lavrnja, Irena Božić, Biljana 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=29 https://fedorabg.bg.ac.rs/fedora/get/o:2285/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41536015 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:30 2021-03-11T00:00:00Z 1

Molekularna i morfološka karakterizacija vrsta iz kompleksa Praon dorsale- yomenae (Hymenoptera, Braconidae) Molecular and morphological characterization in Praon dorsale- yomenae species complex (Hymenoptera, Braconidae) Mitrovski Bogdanović, Ana S. 1979- „Dorsale-yomenae“ kompleks vrsta, geometrijska morfometrija, tradicionalna morfometrija, COI mtDNK, 28S D2 „Dorsale-yomenae“ species complex, geometric morphometry, traditional morphometry, COI mtDNA, 28S D2 Datum odbrane: 21.07.2012. Molekularna i morfološka varijabilnost unutar kompleksa vrsta Praon dorsale-yomenae analizirana je primenom tri nezavisne metode: “tradicionalne” morfometrije, geometrijske morfometrije i analize citohrom oksidaza I sekvenci mitohondrijalne DNK i 28S D2 gena nuklearne DNK. Za morfometrijske analize korišćena je 421 jedinka (270 ţenki i 151 muţjak) sakupljena sa preko 30 razliĉitih afidnih domaćina širom Palearktika. Molekularne analize su obuhvatile 47 jedinki u asocijaciji sa razliĉitim domaćinima. Primenom diskriminantne kanonijske analize utvrĊeno je koji su karakteri dovoljno informativni za morfološku diferencijaciju analiziranih taksona. CVA analizom su prikazane razlike u obliku krila izmeĊu vrsta. Varijabilnost oblika krila meĊu biotipovima analizirana je primenom PCA. Pokazano je da postoji znaĉajan efekat domaćina na varijabilnost oblika krila meĊu biotipovima vrsta P. dorsale i P. longicorne, dok je meĊu biotipovima vrste P. yomenae utvrĊen znaĉajan efekat geografske distribucije. Analize oblika krila ukazale su na to da se vrste „dorsale-yomenae“ kompleksa mogu morfološki razlikovati na osnovu duţine radijalnog i povratnog nerva. Geometrijska morfometrija primenjena u cilju vizualizacije suptilnih razlika u obliku krila pokazala je veću osetljivost u razdvajanju analiziranih taksona „dorsale-yomenae“ grupe u odnosu na „tradicionalnu” morfometriju. Ispitali smo validnost prethodno korišćenih morfoloških karaktera u identifikaciji „dorsale-yomenae“ grupe. TakoĊe smo ukazali na nove karaktere koji se mogu koristiti u kljuĉevima za identifikaciju. UtvrĊeni su razliĉiti obrasci obojenosti krilne nervature unutar kompleksa vrsta „dorsale-yomenae“. Na osnovu rezultata molekularnih analiza potvrĊen je status vrsta P. longicorne, P. dorsale, P. yomenae i P. volucre. UtvrĊeni su novi domaćini/asocijacije za vrstu P. dorsale. Otkrivena je nova vrsta za nauku koja parazitira vaš Staticobium limonii na Limonium angustifolium. Vrsta P. megourae nije dobila molekularnu potvrdu pa su za rasvetljavanja statusa ovog taksona potrebna dodatna istraţivanja. Molecular and morphological variability of Praon dorsale-yomenae species complex was analyzed using the three independent methods: “traditional” morphometrics, geometric morphometrics and DNA sequence analysis of two gene regions (COI mtDNA and 28S D2). For morphometric analysis we used 421 specimens (270 females and 151 males) reared from about 30 different species of aphid hosts throughout Palaearctic. Molecular analysis included 47 specimens in association with different aphid hosts. Discriminant Canonical Analysis was performed in order to determine which characters were informative for morphological diferentiation of analyzed taxa. To explore differences in wing shape between species we performed Canonical Variate Analysis. Variation in wing shape among biotypes was investigated using Principal Component Analysis. We found that great variablity in wing shape of P. dorsale and P. longicorne biotypes was influenced by the host, while great effect of geographical distribution was noticed between P. yomenae biotypes. Analysis of wing shape demonstrated that „dorsale-yomenae“ species can be morphologically discriminated on the basis of length of forewing radial and recurrent vein. Geometric morphometrics applied to visualize subtle shape differences had more sensitivity than „traditional“ morphometrics in distiguishing taxa within „dorsale-yomenae“ group. We tested the validity of morphological characteristics previously used for identification in „dorsale-yomenae“ group, also indicating a new characters that could be used in identification keys. Different colour patterns of wing venation in „dorsale-yomenae“ species complex were found. On the basis of molecular results P. longicorne, P. dorsale, P. yomenae and P. volucre was confirmed as separate species. We presented a new tritrophic association for P. dorsale. A new parasitoid species from Staticobium limonii infesting Limonium angustifolium was described. P. megourae was not confirmed as separate species using molecular markers, thus the clarification of its status requires further research. Univerzitet u Beogradu Biološki fakultet Tomanović, Željko Mitrović, Milana Ivanović, Ana Blesić, Bela Vorburger, Christoph 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=30 https://fedorabg.bg.ac.rs/fedora/get/o:2300/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024495538 sr Autorstvo-Nekomercijalno 3.0 Srbija (CC BY-NC 3.0)

oai:eteze.bg.ac.rs:31 2013-09-25T00:00:00Z 1

Histološke i ultrastrukturne promene hipofize i nadbubrežnih žlezda pacova u uslovima akutnog toplotnog stresa Histological and ultrastructural changes in the pituitary and adrenal glands of rats under acute heat stress Petrović-Kosanović, Dragana Ž. 1976- Akutni toplotni stres, pacov, hipofiza, nadbubrežne žlezde, histologija, ultrastruktura Acute heat stress, rat, pituitary, adrenal glands, histology, ultrastructure Datum odbrane: 09.09.2012. Ispitivan je uticaj akutnog toplotnog stresa na histološke, imunohistohemijske, ultrastrukturne, stereološke i biohemijske karakteristike adrenokortikotropnih ćelija hipofize i ćelija nadbubrežnih žlezda pacova kao ciljnih organa hipotalamo-hipofizne-adrenalne osovine u odgovoru na dejstvo stresora. Pacovi mužjaci soja Wistar izlagani su temperaturi od 38C u komori u trajanju od 60 minuta. Životinje su nakon tretmana žrtvovane dekapitacijom u prepodnevnim časovima, u približno isto vreme, da bi se izbegao uticaj cirkadijalnog ritma na proučavane parametre. Kortikotropne ćelije adenohipofize su analizirane na nivou svetlosne i transmisione elektronske mikroskopije primenom imunohistohemijskih i stereoloških metoda. U nadbubrežnim žlezdama ispitivane su histološke i ultrastrukturne karakteristike ćelija kore i srži. Kvantitativne odlike nadbubrežnih žlezda određivane su primenom stereoloških i morfometrijskih metoda na nivou svetlosne i elektronske mikroskopije. Peptidergički neuroni (VIP, SP i NPY) u kori i srži nadbubrežnih žlezda procenjivani su imunohistohemijskim metodama. Za prikazivanje protoka krvi u nadbubrežnim žlezdama korišćena je Noveli histološka metoda bojenja. Ćelije u proliferaciji procenjivane su preko Ki-67 antigena, dok je za detekciju apoptotskih ćelija nadbubrežnih žlezdi primenjeno bojenje propidijum-jodidom. Određivane su i koncentracije adrenokortikotropnog hormona hipofize (ACTH), kao i kortikosterona, aldosterona, adrenalina i noradrenalina nadbubrežnih žlezda pacova u cirkulaciji. U hipofizi, primenjeni tretman doveo je do povećanog izlučivanja ACTH iz kortikotropnih ćelija. Ovo se na nivou svetlosne mikroskopije manifestovalo smanjenjem broja ćelija imunopozitivnih na ACTH, a na nivou elektronske mikroskopije smanjenjem broja granula u ACTH ćelijama. U skladu sa tim, biohemijski podaci pokazali su da je koncentracija ACTH u cirkulaciji povećana. U krvnim sudovima hipofize prisutna je agregacija krvnih pločica... The aim of the study was the effect of acute heat stress on the histological, immunohistochemical, ultrastructural, stereological and biochemical characteristics of corticotroph pituitary cells and cells of the adrenal glands of rats as a target organ of the hypothalamic-pituitary-adrenal axis in response to the effects of stressors. Wistar male rats were exposed to a temperature of 38C in the chamber for 60 minutes. Animals were sacrificed by decapitation after treatment in the morning, at about the same time, in order to avoid the influence of circadian rhythm on the studied parameters. Corticotroph pituitary cells were analyzed at the level of light and by transmission electron microscopy using immunohistochemical and stereological methods. The adrenal glands were studied by histological and ultrastructural characteristics of the cells of cortex and medulla. Quantitative characteristics of the adrenal glands were determined using stereological and morphometric methods at light and electron microscopy. Peptide neurons (VIP, SP and NPY) in the cortex and medulla of the adrenal glands were assessed by immunohistochemical methods. To show the flow of blood to the adrenal glands a Novelli histological method of staining was used. The cells in proliferation were assessed by Ki-67 antigen, whereas the detection of apoptotic cells of the adrenal gland was enabled by propidium-iodide staining. The concentration of pituitary adrenocorticotropic hormone (ACTH) and corticosterone, aldosterone, adrenaline and noradrenaline in the rat adrenal gland circulation were determined. In the pituitary, the applied treatment resulted in increased secretion of ACTH from corticotroph cells. On the level of light microscopy, it was demonstrated by decreased number of immunopositive ACTH cells, and at the level of electron microscopy by reduced number of granules in the ACTH cells. Accordingly, biochemical data showed that the concentration of ACTH in the circulation increased. The blood vessels of the pituitary gland in platelet aggregation were present... Univerzitet u Beogradu Biološki fakultet Koko, Vesna Milošević, Verica Budeč, Mirela Čakić Milošević, Maja 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=31 https://fedorabg.bg.ac.rs/fedora/get/o:2305/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024496306 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:32 2012-11-09T00:00:00Z 1

Fitohemijska i genetička varijabilnost vrsta iz sekcije Serpyllum (Mill.) Benth. roda Thymus L. (Lamiaceae) u Srbiji Phytochemical and genetical variability of species from section Serpyllum (Mill.) Benth. genus Thymus L. (Lamiaceae) in Serbia Šoštarić, Ivan I., 1971- Thymus, etarska ulja, hemotip, površinski flavonoidi, AFLP, genetiĉki diverzitet, retikulatna evolucija.serpyllum Thymus, essential oil, chemotype, surface flavonoids, AFLP, genetic diversity, reticulate evolution Datum odbrane: 28.09.2012. Rod Thymus je po broju vrsta jedan od najznaĉajnijih u okviru familije Lamiaceae. U zavisnosti od pristupa autora broj vrsta unutar roda varira, meĊutim ukoliko se izabere pristup minimalne varijabilnosti, prema raspoloţivim podacima opisano je 215 vrsta ovog roda. Vrste ovog roda podeljene su u osam sekcija. U flori Srbije opisana je, do sada, 31 vrsta i preko 100 infraspecijskih taksona, koje sve pripadaju podsekciji Serpyllum, sa izuzetkom vrsta Thymus comptus i Th. striatus (Sect. Hyphodromi) i Th. vulgaris (Sect. Thymus). Reproduktivna izolacija izmeĊu vrsta ovog roda je izuzetno slaba što ĉini taksonomska istraţivanja još teţim. Vrste roda Thymus koriste se kao lekovite i aromatiĉne biljke u tradicionalnoj i zvaniĉnoj medicini u svim krajevima u kojima se javljaju. Cilj ovog rada je bio da se opišu razliĉiti hemotipovi unutar vrsta i populaciju ovog roda kao i da se analizom površinskih flavonoida i AFLP markera poboljša uvid u genetiĉke i evolutivne odnose izmeĊu populacija vrsta ovog roda sa podruĉja Srbije. U ovo istrţivajne ukljuĉene su populacije vrsta Th. pulegioides (Subsect. Alternantes), Th. glabrescens, Th. maschallianus i Th. pannonicus (Subsect. Isolepides), Th. balcanus i Th. praecox (Subsect. Peudomarginati) Analiza sastava etarskih ulja vršena je pomoću TD-GC-MS sistema, a jedinjenja su odreĊen uporeĊivanjem RI i/ili masenog spektra sa literaturnim podacima. Identifikovana su ukupno 103 jedinjenja. Identifikovane su, po brojnosti, tri glavne grupe jedinjenja: seskviterpenski ugljovodonici, oksigenovani monoterpenski ugljovodonici i monoterpenski ugljovodonici. Statistiĉka obrada sastava etarskih ulja ukljuĉila je korelacije, analizu glavnih komponenti i klaster analizu. Statistiĉka obrada je pokazala da se, po relativnoj zastupljenosti jedinjenja, mogu razlikovati geraniolni, fenolni, germakren-D, citralni, linaloolni, (E)-kariofilen, α-terpinil acetat i linalil acetatni hemotip. In terms of the number of species, the genus Thymus is one of the most important genera within the Lamiaceae family. The number of species may vary depending on the approach of the author, but if the concept of minimal variability is chosen 215 species have been described. This genus is divided into 8 sections. In Flora of Serbia, 31 species and more than 100 ifraspecific taxa have been described, all of which belong to section Serpyllum, except Thymus comptus and Th. striatus (Sect. Hyphodromi) and Th. vulgaris (Sect. Thymus). Reproductive isolation between species seems to be weak, which makes taxonomical studies in this genus even more difficult. Species of genus Thymus are used as aromatic and medicinal plants in both traditional and modern medicine in all regions where they grow. The aim of this work was to describe different chemotypes within species and population of this genus and, by analysis of surface flavonoids and AFLP markers, provide better insight into genetic and evolutional relationships among the populations and species of the genus Thymus from Serbia. This work included populations of Th. pulegioides (Subsect. Alternantes), Th. glabrescens, Th. maschallianus and Th. pannonicus (Subsect. Isolepides), Th. balcanus and Th. praecox (Subsect. Peudomarginati). Analysis of essential oils was done by TD-GC-MS system, and compounds were identified by comparing RI and/or mass spectra with published data. 103 compounds were identified. Three major group of essential oil compounds were identified: monoterpene hydrocarbons, oxygenated monoterpene hydrocarbons and sesquiterpene hydrocarbons. Based on relative abundance of compounds, Corelation, PCA and Cluster analysis were performed, and it revealed the existence of several chemotypes, such as geraniol, phenol, germacrene-D, citral, linalool, (E)-caryophyllene, α-terpinyl acetate and linalyl acetate chemotype. Univerzitet u Beogradu Biološki fakultet Marin, Petar Dajić Stevanović) Janaćković, Peđa 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=32 https://fedorabg.bg.ac.rs/fedora/get/o:2318/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41536783 sr Autorstvo-Nekomercijalno-Deliti pod istim uslovima 3.0 Srbija (CC BY-NC-SA 3.0)

oai:eteze.bg.ac.rs:33 2012-11-09T00:00:00Z 1

Variranje odnosa polova, polnog dimorfizma i komponenti adaptivne vrednosti u populacijama Mercurialis perennis L. (Euphoriaceae) duž gradijenta nadmorske visine Variation in sex ratio, sexual dimorphism, and fitness components in populations of Mercurialis perennis L. (Euphorbiaceae) along the altitudinal gradient Jovanović, Vladimir M. 1981- Mercurialis perennis, odnos polova, polni dimorfizam, reproduktivno ulaganje, evoluciona ekologija, citogeografija Mercurialis perennis, sex ratio, sexual dimorphism, reproductive allocation, evolutionary ecology, cytogeography Datum odbrane: 29.09.2012. Vrste roda Mercurialis su se pokazale kao atraktivan objekat za raznovrsna ekološka, genetička i istraţivanja u evolucionoj biologiji biljaka. Šumski prosinac, Mercurialis perennis L., je višegodišnja zeljasta anemofilna i dvodoma vrsta, karakteristična za primarna ili manje narušena šumska staništa. Analiza populacija ove vrste sa različitih nadmorskih visina pruţila je mogućnost da se na relativno malom geografskom prostoru istraţi uticaj velikog raspona variranja ekoloških faktora na morfološke karakteristike i reproduktivnu alokaciju (RA) kod pripadnika različitih polova, kao i na brojčani odnos polova u populaciji. Istraţivanje je obuhvatilo populacije sa 14 lokaliteta u Srbiji, koje su uzorkovane u periodu 2006–2009. Statistički značajno odstupanje od pretpostavljenog ravnoteţnog odnosa polova ustanovljeno je u 69,5% populacionih uzoraka. Broj uzoraka sa neravnoteţnim odnosom polova varirao je meĎu godinama, a u većini istraţenih populacija neravnoteţa je bila u korist muških biljaka. Neravnoteţa u korist muških biljaka ustanovljena je i u istraţivanjima na drugim populacijama ove vrste, a ovakav obrazac neravnoteţe polova se smatra uobičajenim za višegodišnje dvodome biljke. Indeks polnog dimorfizma je kod većine analiziranih osobina imao male do umerne vrednosti, dok su izrazito i dosledno dimorfne bile one osobine koje su direktno povezane sa reprodukcijom – broj cvetova i masa cvasti. Smer polnog dimorfizma razlikuje se kod ovih osobina. Muški pol produkuje više cvetova, što ukazuje na pojačanu intraseksualnu selekciju u muškom polu za veću produkciju polena. S druge strane, masa ţenskih cvasti je višestruko veća od mase muških cvasti, što se preslikava i u veću reproduktivnu alokaciju ţenskih jedinki. U ţenskom polu je detektovan i obrazac smanjenja ulaganja u reprodukciju sa povećanjem nadmorske visine na kojoj biljka raste. Analize polnog dimorfizma u visini biljke pokazale su da je u većini populacionih uzoraka muški pol viši, što se uklapa u pretpostavke hipoteze disperzije polena... The plant species of genus Mercurialis are very attractive object for various ecological, genetical and evolutionary researches. Dog’s mercury, Mercurialis perennis L., is a perennial anemophilous and dioecious herb, which usually grows in old and undisturbed forests. The analyses of populations of dog’s mercury from various altitudes gave us opportunity to investigate the effect of great environmental variation on morphological traits, reproductive allocation in different sexes, as well as on sex ratios in populations. This research included populations from 14 localities in Serbia sampled in 2006–2009. Statistically significant bias in sex ratio was found in 69.5% of population samples. Number of samples with biased sex ratio varied among years, and the majority of samples were male-biased. The male-biased populations of dog’s mercury were found elsewhere, and this pattern of bias is regarded to as the common one in dioecious perennials. Sexual dimorphism index for greater part of analysed traits had small to moderate values, while reproductive traits (number of flowers, mass of inflorescences) were markedly and consistently dimorphic. The range and direction of dimorphism differed in these reproductive traits. Males produced more flowers, and this information indicates pronounced intrasexual selection in males for greater pollen production. On the other hand, mass of female inflorescences was manifold bigger than mass of male inflorescences, and female reproductive allocation was bigger in a similar manner. In females, we also found pattern of decrease in reproductive allocation with the increase of altitude. The analyses of sexual dimorphism in plant size showed that males were the higher sex in majority of population samples. This is in agreement with pollen-dispersal hypothesis... Univerzitet u Beogradu Biološki fakultet Cvetković, Dragana Blagojević, Jelena Jovanović, Slobodan 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=33 https://fedorabg.bg.ac.rs/fedora/get/o:2320/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024510642 sr Autorstvo-Nekomercijalno-Deliti pod istim uslovima 3.0 Srbija (CC BY-NC-SA 3.0)

oai:eteze.bg.ac.rs:34 2013-09-19T00:00:00Z 1

Strukturna i funkcionalna analiza gena za alfa-1-antitripsin u bolestima pluća čoveka Structural and functional analysis of alpha-1-antitrypsin gene in human lung diseases Ljujić, Mila V., 1980- Alfa-1-antitripsin, emfizem pluća, karcinom pluća, retke varijante, G320R, V321F, inhibitorna aktivnost, polimerizacija, termostabilnost Alpha-1-antitrypsin, emphysema, lung cancer, rare variants, G320R, V321F, inhibitory activity, polymerization, thermostability Datum odbrane: 12.07.2012. Alfa-1-antitripsin je inhibitor serin proteaza čija je osnovna biološka funkcija inhibicija elastaze neutrofila – enzima koji učestvuje u degradaciji elastina i koji dovodi do oštećenja tkiva pluća. Deficijencija i disfunkcija alfa-1-antitripsina leže u osnovi više oboljenja od kojih su najčešći emfizem pluća i oboljenja jetre, a mogu predstavljati i faktor rizika za nastanak karcinoma pluća. Ovaj rad je imao za cilj da ispita postojanje strukturnih promena u kodirajućim egzonima gena za alfa-1-antitripsin kod ispitanika sa emfizemom pluća i kod ispitanika sa karcinomom pluća, kao i da istraži funkcionalne posledice otkrivenih promena i njihov eventualni značaj u nastanku i razvoju bolesti. Strukturnom analizom gena za alfa-1-antitripsin DGGE metodom i DNK sekvenciranjem detektovano je prisustvo deficijentnih varijanti Z, S i Mmalton, kao i dve nove varijante označene kao G320R i V321F. Elektroforezom u denaturišućem poliakrilamidnom gelu uočeno je da varijante G320R i V321F migriraju brže u odnosu na WT varijantu, a analizom u denaturišućem poliakrilamidnom gelu sa 5M ureom pokazano je da ove varijante verovatno imaju smanjenu hidrofobnost u odnosu na WT varijantu. Analizom formiranih kompleksa između alfa-1-antitripsina i elastaze pankreasa u SDS gelovima, utvrđeno je da se inhibitorna aktivnost ispitivanih varijanti ne razlikuje od inhibitorne aktivnosti WT varijante proteina. Nativna elektroforeza preparata alfa-1-antitripsina inkubiranih na različitim temperaturama pokazala je da mutirane varijante proteina imaju blago smanjenu termostabilnost u odnosu na WT protein, a elektroforeza proteina eksprimiranih u COS7 ćelijskoj liniji pokazala je da varijante G320R i V321F pod fiziološkim uslovima ne formiraju polimere. Metodom imunofluorescencije na tranzijentno transfekovanim COS7 ćelijama pokazano je da su varijante G320R i V321F, kao i WT protein, lokalizovane u Goldžijevom aparatu i da se ne zadržavaju u endoplazmatičnom retikulumu... Alpha-1-antitrypsin is a serine protease inhibitor whose main biological function is inhibition of neutrophil elastase – enzyme capable of digestion of elastin and involved in lung tissue destruction. Deficiency and disfunction of alpha-1-antitrypsin is associated with emphysema and liver disease, and can represent a risk factor for development of lung cancer. The objective of this work was to perform structural analysis of alpha-1-antitrypsin gene in subjects with emphysema and lung cancer, as well as to perform functional analysis of discovered variants in order to estimate their role in disease development. Structural analysis of alpha-1-antitrypsin gene, using DGGE and DNA sequencing, revealed presence of deficient variants Z, S and Mmalton, as well as two novel variants – G320R and V321F. Denaturing PAGE analysis showed that variants G320R and V321F exibited increased gel mobility compared to WT variant, and electrophoresis in the presence of 5M urea showed that these variants effected the protein structure, probably by changing its hydrophobicity. Nondenaturing electrophoresis of heat treated proteins showed that both variants had slightly decreased thermostability when compared to WT variant and non-denaturing PAGE of COS7 expressed proteins showed that these variants did not form polymers under physiological conditions. Inibitory activity of variants G320R and V321F, determined by analysis of SDS-PAGE resistant complexes between alpha-1-antitrypsin and porcine pancreas elastase, was same as in WT variant. Immunofluorescence of transiently transfected COS7 cell line showed that variants G320R and V321F, as well as WT protein, were predominantly localized at Golgi apparatus indicating that they are not retained in endoplasmic reticulum... Univerzitet u Beogradu Biološki fakultet Radojković, Dragica Matić, Gordana Divac, Aleksandra Topić, Aleksandra 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=34 https://fedorabg.bg.ac.rs/fedora/get/o:2322/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41542159 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:35 2013-09-19T00:00:00Z 1

Konzervirana svojstva proteina virusa hepatitisa C genotipa 1b kao prognostičkih markera odgovora na kombinovanu terapiju pegilovanim interferonom i ribavirinom Conserved properties of hepatitis C genotype 1b proteinsas prognostic markers of response to pegylated interferon and ribavirin combination therapy Jovanović-Ćupić, Snežana P., 1970- Hepatitis C virus (HCV), bioinformatika, metod informacionih spektara, proteinske sekvence Hepatitis C virus (HCV), Bioinformatics, Informational spectrum method, Protein sequence Datum odbrane: 10.07.2012. Uvod: Infekcija virusom hepatitisa C (HCV) predstavlja značajan globalni zdravstveni problem koji često vodi ka hroničnoj bolesti jetre i cirozi. Prema podacima Svetske zdravstvene organizacije registrovano je preko 170 miliona ljudi inficiranih virusom HCV. Sadašnja standardna terapija hroničnog HCV-a kod pacijenata inficiranih genotipom 1b, koji predstavlja najčešći genotip kako u SAD, zapadnoj Evropi i Srbiji, se sastoji od pegilovanog interferona u kombinaciji sa ribavirinom. Međutim, kombinovana terapija je praćena brojnim neželjenim efektima i dovodi do stabilnog virusološkog odgovora samo kod 50% pacijenata inficiranih genotipom 1. Stoga bi jednostavan i pouzdan test, koji bi pre početka terapije mogao da predvidi virusološki odgovor, bio od velike koristi u kliničkoj praksi. Metode: Identifikacija konzervirane informacije sadržane u proteinima HCV koja korelira sa odgovorom na standardnu kombinovanu terapiju rađena je bioinformatičkom analizom. Uzorci plazme 48 pacijenata sa hroničnom infekcijom HCV, genotipa 1b su klasifikovani u odnosu na odgovor na kombinovanu terapiju. Za određivanje primarne strukture proteina HCV primenjene su klasične metode molekularne biologije: reverzna transkripcija i lančana reakcija polimeraze (Rt-PCR), apsolutna kvantifikacija sa PCR-om u realnom vremenu i automatsko sekvenciranje. Rezultati: Na osnovu rezultata analize svih proteina virusa HCV utvrđeno je da je informacioni sadržaj proteina p7 u korelаciji sа odgovorom nа kombinovаnu terаpiju. Rezultati dobijeni analizom proteinskih sekvenci, 48 pacijenata sa teritorije Srbije su u saglasnosti sa predloženim bioinformatičkim kriterijumom. Posebna pažnja je posvećena optimizaciji eksperimentalnih protokola i formiranju homogenenih grupa u odnosu na osobenosti virusa (tip i podtip) i odgovora na antivirusnu terapiju pacijenata. Zaključak: Na osnovu rezultata ove studije predložen je bioinformatički kriterijum koji omogućаvа procenu odgovora hroničnih HCV bolesnikа inficirаnih genotipom 1b nа kombinovаnu terаpiju. Background: Hepatitis C virus (HCV) infection is a major and rising global health problem, affecting about 170 million people worldwide, according to WHO data, and often leading to chronic liver disease and cirrhosis. The current standard therapy for chronic HCV infection with pegylated interferon combined with ribavirin in patients with the genotype 1 infection, the most frequent genotype in the USA, Western Europe and Serbia, accompanied by numerous side effects, leads to a successful outcome in only about 50% of individuals. Therefore, simple and accurate prediction of hepatitis C treatment response is of great benefit to patients and clinicians. Methods: Identification of the conserved information of the HCV proteins that correlate with the combination therapy outcome was performed by bioinformatics analysis. Plasma samples of 48 chronic HCV patients from Serbia were classified according to the outcome of therapy. To determine primary structure of HCV proteins classical methods of molecular biology: reverse transcription and polymerase chain reaction (Rt-PCR), the absolute quantification-Real Time PCR and DNA sequencing were applied. Results: Among the HCV proteins that we have analyzed the informational property of the p7 of HCV genotype 1b was best related to the therapy outcome. Findings obtained from analyzing sequences 48 patients collected from Serbia were in perfect agreement with proposed bioinformatics criterion. Special attention was paid to optimization experimental protocols and forming homogeneous groups of patients regarding HCV genotype (type and subtype) and therapy response. Conclusions: On the basis of the results in the present study, a simple bioinformatics criterion that could be useful in assessment of the response of HCV-infected patients to the combination therapy has been proposed. Univerzitet u Beogradu Biološki fakultet Glišić, Sanja Brajušković, Goran Stanojević, Maja Nožić, Darko 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=35 https://fedorabg.bg.ac.rs/fedora/get/o:2323/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41538575 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:36 2012-11-19T00:00:00Z 1

Uticaj fulerenola na učestalost hromozomskih aberacija i mikronukleusa u ćelijskoj liniji CHO-K1 ovarijuma hrčka i u kulturi limfocita periferne krvi čoveka The influence of fullerenol on the frequency of chromosome aberrations and micronuclei in ovarian hamster cell line CH0-K1 and in human peripheral blood lymphocites cell culture Mrđanović, Jasminka Ž. 1971- Nanočestice, fulereni, fulerenol, genotoksičnost, mikronukleusi, hromozomske aberacije Nanoparticles, fullerenes, fullerenol, genotoxicity, micronuclei, chromosomal aberrations Datum odbrane: 16.07.2012. Nanomaterijali zahvaljujući svojim malim dimenzijama i raznovrsnim fizičkohemijskim osobinama imaju velik potencijal za primenu u različitim oblastima života. Među nanočestice sa širokom upotrebom u biomedicini ubraja se fuleren C60. Njegova slaba vodorastvorljivost može se prevazići derivatizacijom, pri čemu fuleren stiče nova svojstva koja utiču na njegovu funkcionalnost. Najpoznatiji vodorastvorni derivati C60 su fulerenoli (С60(ОН)n, n=2-40), koji imaju velik potencijal za primenu u medicini. Taj potencijal je baziran na njihovoj sposobosti da u biološkim sistemima skupljaju slobodne radikale nastale u oksidativnom stresu. Međutim, sa druge strane, fulerenoli imaju sposobnost da pod određenim uslovima deluju prooksidativno. Zbog toga je neophodno definisanje koncentracija i uslova pod kojima fulerenol i njegovi derivati deluju kao antioksidanti odnosno prooksidanti. Taj aspekt je veoma važan zbog uticaja ovih nanočestica na DNK i određuje u velikoj meri njihova genotoksična odnosno antigenotoksična svojstva. Pored uticaja koncentracije nanočestica na oksidativni status, na genotoksičnost utiču i fizičkohemijske karakteristike samih nanočestica kao što su: veličina, oblik, površinsko naelektrisanje, čistoća, rastvorljivost, površinske modifikacije i agregacija, koje je takođe potrebno precizno definisati. Konačno, ispitivanje uticaja novosintentisanih supstanci sa potencijalom za medicinsku aplikaciju na DNK, predstavlja neophodan korak pre faze kliničkih studija. Zbog svega navedenog, primarni cilj ovog rada jeste ispitivanje genotoksičnih odnosno antigenotoksičnih svojstava vodorastvornog fulerenskog derivata fulerenola C60(OH)24, na dva različita sisarska modela. Prvi model je ćelijska kultura ovarijuma kineskog hrčka CHO-K1, a drugi primarna ćelijska kultura humanih limfocita. U radu su evaluirane fizičkohemijske karakteristike nanočestice fulerenola C60(OH)24 u medijumu za ćelijske kulture sa serumom i to u uslovima koji odgovaraju 6 eksperimentalnim uslovima u testovima mikronukleusa i hromozomskih aberacija. Zatim je ispitan uticaj fulerenola na preživljavanje ćelija u cilju utvrđivanja subcitotoksičnih koncentracija fulerenola, potrebnih za ispitivanje genotoksičnosti i antigenotoksičnosti fulerenola. Nakon toga je izvršena evaluacija incidencije biomarkera oštećenja DNK radi utvrđivanja genotoksičnog potencijala fulerenola. U poslednjem segmentu rada je evaluacijom istih biomarkera analiziran i antigenotoksičan potencijal fulerenola, na ćelijskim kulturama koje su prethodno oštećene poznatim citostatskim agensom mitomicinom C. Rezultati analiza su pokazali da je C60(OH)24 dimenzija od 40-180 nm u zavisnosti od kosolventa, kao i da gradi stabilne nanočestice u medijumu za ćelijsku kulturu sa fetalnim goveđim serumom. Citotoksičnost fulerenola kreće se u opsegu koncentracija od 88,6 μM-443,2 μM. Analizom genotoksičnosti fulerenola testom mikronukleusa i hromozomskih aberacija pokazano je da fulerenol nije bio genotoksičan u ispitivanim ćelijskim kulturama, pri ispitivanim subcitotoksičnim koncentracijama i pri datim vremenskim tretmanima. Ispitivanje antigenotoksičnog potencijala je pokazalo da fulerenol utiče na snižavanje ispitivanih biomarkera oštećenja DNK. Nanomaterials, due to their small dimensions and manifold physicochemical characteristics have great potential for application in various areas of life. One of nanoparticles with wide implementation in biomedicine is fullerene C60. Its weak water solubility can be overcome by derivatization after which fullerene acquires new characteristics, which affect its functionality. The most famous water soluble C60 derivatives are fullerenols (С60(ОН)n, n=2-40), which have great potential for implementation in medicine. This potential is based on their ability to collect free radicals occurring in oxidative stress in biological systems. However, on the other hand, fullerenols are able to act prooxidatively under certain conditions. Thus, it is necessary to define concentrations and conditions under which fullerenol and its derivatives act as antioxidants, i.e. prooxidants. This aspect is very important because of the impact of these nanoparticles to the DNA, which largely defines their genotoxic i.e. antigenotoxic characteristics. Besides the impact of nanoparticles’ concentration to oxidative status, genotoxicity is also affected by physicochemical characteristics of nanoparticles themselves: their size, shape, surface charge, purity, solubility, surface modifications and aggregation, which are all necessary to be precisely defined. Finally, the testing of the impact of newly synthesized substances with potential for medical application to DNA, represents a necessary step before the phase of clinical trials. Due to all the above state, the primary aim of this paper was to test genotoxic i.e. antigenotoxic characteristic of water-soluble fullerene derivative fullerenol C60(OH)24, in two different mammalian models. The first model was an ovarian cell culture of a Chinese hamster CHO-K1, and the other was a primary humane lymphocyte cell culture. The paper evaluated physicochemical characteristics of fullerenol nanoparticle C60(OH)24 in the cell culture medium with serum under the conditions which were in accordance with the experimental conditions in micronuclei and chromosomal 8 aberrations tests. Furthermore, the affect of fullerenol to cell survival was tested with the aim of determination of fullerenol subcytotoxic concentrations, necessary for testing of fullerenol genotoxicity and antigenotoxicity. After that, the DNA damage biomarkers incidence evaluation was performed for determination of fullerenol genotoxicity potential. In the last segment of the paper, the antigenotoxic potential of fullerenol was analyzed by evaluation of the same biomarkers, in cell cultures, which were previously damaged by the known cytostatic agent mitomycin C. The results of the analysis showed that C60(OH)24 dimensions of 40-180nm depended on the cosolvent, and that it crated stable nanoparticles in the cell culture medium with fetal bovine serum. Cytotoxicity of fullerenol varied in the range of concentrations from 88.6 μM-443.2 μM. The analysis of fullerenol genotoxicity by the micronuclei test and chromosomal aberrations test showed that fullerenol was not genotoxic in the tested cell cultures, at given subcytotoxic concentrations and treatment duration. Testing of antigenotoxic potential showed that fullerenol affected the decrease of the tested DNA damage biomarkers. Univerzitet u Beogradu Biološki fakultet Đorđević, Aleksandar Anđelković, Marko 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=36 https://fedorabg.bg.ac.rs/fedora/get/o:2340/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024495794 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:37 2012-11-19T00:00:00Z 1

Analiza učestalosti i tipova mutacija KRAS i BRAF gena u karcinomima kolorektuma u populaciji Srbije Frequency and mutation type analysis of KRAS and BRAF genes in colorectal carcinomas in Serbian population Jakovljević, Ksenija V. 1981- Kolorektalni karcinom, KRAS gen, BRAF gen, mutacije Colorectal carcinoma, KRAS gene, BRAF gene, mutations Datum odbrane: 09.07.2012. Uvod: Kolorektalni kancer (CRC) se po svojoj učestalosti i smrtnosti nalazi u samom vrhu svih kancera kod oba pola, kako u svetu, tako i u Srbiji. Za ranu kancerogenezu ovog maligniteta karakteristične su somatske genske promene KRAS i BRAF protoonkogena. Mutacije ovih gena predstavljaju molekularne biomarkere odgovora na ciljanu terapiju, dok su rezultati o njihovoj ulozi kao prognostičkih i prediktivnih faktora kontradiktorni. Podaci o učestalosti i tipu pojedinačnih KRAS i BRAF mutacija kod CRC-a u našoj zemlji su malobrojni, a njihova veza sa kliničko-histopatološkim karakteristikama tumora, karakteristikama bolesnika i tokom bolesti nije dovoljno ispitana. Cilj: Utvrđivanje prisustva, učestalosti i tipa KRAS mutacija i specifične BRAF p.V600E mutacije kod bolesnika sa CRC-om u populaciji Srbije i povezanost prisustva i tipa ovih mutacija sa kliničko-histopatološkim karakteristikama tumora i karakteristikama bolesnika. Takođe, ispitivanje navedenih mutacija kao prediktivnih biomarkera adjuvantne i EGFR-ciljane terapije. Materijal i metode: U radu je analizirano 188 parafinskih uzoraka karcinoma kolorektuma. DNK je izolovana komercijalnim kitom za izolaciju genomske DNK iz parafinskih tkiva (QIAamp® DNA FFPE Tissue kit, QIAGEN). Detekcija prisustva i tipa mutacija kodona 12 i 13 KRAS gena urađena je pomoću dva dijagnostički validirana testa bazirana na eseju lančane reakcije polimeraze (PCR) u realnom vremenu (DxS TheraScreen K-RAS PCR kit, QIAGEN) i PCR reakciji praćenoj reverznom hibridizacijom (KRAS StripAssayTM, ViennaLab Diagnostics). Detekcija p.V600E mutacije u BRAF genu urađena je analizom krive topljenja (HRM) PCR produkta i metodom direktnog sekvenciranja. Za statističku obradu podataka korišćeni su Fišerov egzaktni, χ2 i Log-Rank testovi... Introduction: Colorectal cancer (CRC) incidence and mortality rates are among the highest in both sexes worldwide, as well as in Serbia. The early carcinogenesis of this malignancy is characterized by somatic gene alterations of KRAS and BRAF protooncogenes. Mutations of these genes represent molecular biomarkers of response to targeted therapy, while their roles as prognostic and predictive factors are still contradictory. There are few data about the frequency and types of single KRAS and BRAF mutations in CRC in our country, and their correlation with clinicohistopathological characteristics of tumor, characteristics of patients and the course of disease is still to be established. Aim: Determination of presence, frequency and types of KRAS mutations and specific BRAF p.V600E mutation in CRC patients in Serbian population and correlation of presence and types of these mutations with tumor clinicohistopathological characteristics and patient characteristics. Also, the examination of specified mutations as potential predictive biomarkers of adjuvant and EGFR-targeted therapy. Material and methods: In this study 188 CRC paraffin samples were analyzed. DNA was extracted using the commercial kit for genomic DNA isolation from paraffin tissues (QIAamp® DNA FFPE Tissue kit, QIAGEN). Detection of presence and types of KRAS codon 12 and 13 mutations was performed with two validated diagnostic tests based on real-time polymerase chain reaction (PCR) assay (DxS TheraScreen K-RAS PCR kit, QIAGEN) and PCR reaction followed by reverse hybridization (KRAS StripAssayTM, ViennaLab Diagnostics). BRAF p.V600E mutation was assessed by high resolution melting (HRM) analysis of PCR products and automatic DNA sequencing. Fisher exact, χ2 and Log-Rank tests were used for statistical analysis... Univerzitet u Beogradu Biološki fakultet Stamenković-Radak, Marina Janković, Radmila Mališić, Emina 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=37 https://fedorabg.bg.ac.rs/fedora/get/o:2342/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024495282 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:38 2012-11-19T00:00:00Z 1

Uticaj propofola na signalni put neurotrofina u prednjem mozgu pacova starih 14 dana Propofol-induced changes in neurotrophic signaling in 14-day-old rat forebrain Popić, Jelena. 1978- Propofol, kora, talamus, rano postnatalno razviće, signalni put neurotrofina, neuroapoptoza, sinaptička plastičnost Propofol, cortex, thalamus, postnatal development, neurotrophic signaling pathway, neuroapoptosis, synaptic plasticity Datum odbrane: 06.07.2012. Neurotrofini čine familiju signalnih molekula sa brojnim uticajima na rast, preživljavanje, diferencijaciju i sinaptičku plastičnost postmitotskih neurona, kako u adultnom mozgu, tako i u mozgu tokom razvića. Neurotrofini (BDNF, NGF) se sa određenim afinitetom vezuju za Trk receptore, iniciraju njihovu dimerizaciju i autofosforilaciju i na taj način se pokreće aktivacija signalnih puteva kao što su PI3K/Akt i MAPK/ERK. Akt i ERK kinaze imaju ključne regulatorne uloge u mozgu u procesima kao što su neuronalna proliferacija, diferencijacija, razviće, migracija, preživljavanje i dugotrajna sinaptička plastičnost. Aktivan (fosforilisan) Akt štiti ćeliju od apoptoze tako što stimuliše ekspresiju proteina koji favorizuju preživljavanje ćelija i sa druge strane inhibira egzekutorske kaspaze. Aktivacija ERK1/2 kinaze pomoviše preživljavanje, međutim u određenim uslovima ERK1/2 može imati i pro-apoptotske odlike. S obzirom da je uloga neurotrofina u neurotoksičnosti koja je indukovana anestezijom tokom ranog postnatalnog razvića pokazana u nekoliko studija, cilj ove doktorske disertacije je bio da se na molekulskom nivou ispitaju promene u signalnom putu neurotrofina koje nastaju u kori i talamusu postnatalnih pacova nakon primene anestetske doze propofola, kao i da se utvrdi potencijal tretmana da indukuje ćelijsku smrt i/ili promene u sinaptičkoj plastičnosti. Nakon jednokratne primene propofola (25 mg/kg i.p.) ispitana je vremenska i prostorna ekspresija neurotrofina BDNF i NGF, njihovih aktiviranih receptora TrkB, TrkA i p75 receptora, kao i nishodnih kinaza Akt i ERK kod 14 dana starih (PND14) pacova. Ispitan je i potencijal propofolskog tretman da indukuje ćelijsku smrt, praćenjem ekspresije TNF-α, TNFR1, aktivnog fragmenta kaspaze-3, njegovog inhibitora XIAP proteina, kao i transkripcionog faktora NFκB. Finalno je ispitivan potencijal propofolskog tretmana da indukuje promene u ekspresiji markera sinaptičke plastičnosti (MAP-2, drebrina, GAP-43, sinaptofizina, sinukleina-1 i N-kadherina). Promene su praćene u kori i talamusu kao primarnim ciljevima dejstva anestetskog delovanja. Primenom sledećih metoda Western blot analize, RT- i PCR-a u realnom vremenu ispitivane su promene u ekspresiji ciljnih proteina i iRNK, a primenom Fluoro-žad B histološkog bojenja analizirana je pojava neurona u degeneraciji... The neurotrophins are a family of secreted proteins that mediate numerous functions in both the developing and mature nervous system, including growth, survival, differentiation and synaptic plasticity of postmitotic neurons. The binding of neurotrophins (BDNF, NGF) to Trk receptors induces their dimerization which is followed by autophosphorylation of tyrosine residues within the intracellular kinase domain, that leads to the activation of signaling pathways such as the PI3K/Akt and MAPK/ERK pathways. Akt and ERK kinases play a crucial role in regulating various processes in the brain, including neuronal proliferation, differentiation, development, migration, survival and long-term synaptic plasticity. Phosphorylated Akt can protect cells from apoptosis via stimulation of the expression of proteins that favor cell survival and by inhibiting executor caspases. Activation of ERK1/2 generally promotes cell survival, although under certain conditions, ERK1/2 can possess proapoptotic properties. Since several studies have revealed a role for neurotrophins in anesthesia-induced neurotoxicity in the developing brain, the goal of this study was to explore the potential of anesthetic dose of propofol to influence neurotrophic signaling pathway in the cortex and thalamus of 14-day-old (PND14) rats, and also to investigate whether same treatment is able to induce neurodegeneration and/or changes in synaptic plasticity. In this study we monitored the spatial and temporal expression of neurotrophic signaling molecules (BDNF, NGF, TrkA, TrkB, p75, Akt and ERK) in the brain of PND14 Wistar rats after the application of a single propofol dose (25 mg/kg i.p). The potential of propofol treatment to induce cell death was also examined, following the expression of TNF-α, TNFR1, cleaved caspase-3 fragment, XIAP and NFκB. Finally, we investigated the changes in the markers of synaptic plasticity (MAP-2, drebrin, GAP-43, synaptophysin, synuclein-1 and N-cadherin) after the propofol treatment. The structures of interest were the cortex and thalamus as the primary areas of anesthetic actions. Changes of the levels of mRNA and proteins of interest were assessed by RT- or Real Time PCR and Western immunoblot analysis at different time points during the first 24 h after the treatment. Fluoro-Jade B staining was used to follow the appearance of degenerating neurons... Univerzitet u Beogradu Biološki fakultet Kanazir, Selma Nedeljković, Nadežda Pešić, Vesna Ruždijić, Sabera 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=38 https://fedorabg.bg.ac.rs/fedora/get/o:2344/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41535247 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:39 2013-09-19T00:00:00Z 1

Uticaj restriktivnog režima ishrane na plastičnost neurona i glije nakon povrede senzomotorne kore mozga pacova Effect of dietary restriction on meuronal and glial plasticity following injury to the rat somatosensory cortex Lončarević-Vasiljković, Nataša, 1977- Povreda mozga, moždana kora, dijetalna restrikcija, pacov Brain injury, cerebral cortex, dietary restriction, rat Datum odbrane: 28.09.2012. Traumatska povreda mozga (engl. traumatic brain injury, TBI) predstavlja povredu moždanog tkiva uzrokovanu mehaničkom povredom glave. TBI je jedan od vodećih uzroka smrtnosti i invaliditeta u svetu, u populaciji ljudi do 45 godina starosti. Posledice TBI zavise od lokalizacije i količine oštećenja moždanog tkiva i mogu varirati od blažih motoričkih i kognitivnih smetnji, pa sve do težih oblika invaliditeta i smrti. Traumatska povreda mozga dovodi do narušavanja krvno-moždane barijere, što rezultuje tačno određenim sledom događaja u povređenom tkivu CNS-a. Naime, akutna faza, označena kao primarna povreda, nastaje direktnim delovanjem mehaničke sile na moždano tkivo i javlja se u trenutku povrede. Događaji koji slede nakon toga označeni su kao sekundarna povreda koja nastaje kao posledica inicijalnog oštećenja, a obuhvata procese koji dovode do daljeg oštećenja tkiva u danima i nedeljama nakon povrede. To su pre svega zapaljenski procesi koji dovode do smrti neurona koji prvobitno nisu bili zahvaćeni mehaničkom povredom. Smatra se da je broj neurona koji umre usled širenja sekundarne povrede daleko veći od broja neurona koji strada usled primarne povrede. Činjenica da se većina procesa u okviru sekundarne povrede odigrava relativno kasno (satima i danima nakon povrede) čini ih podložnim različitim terapeutskim intervencijama. Već decenijama je poznato da restrikcija hrane povoljno deluje na čitav organizam tako što odlaže starosno-zavisne fiziološke promene i smanjuje incidencu različitih obolenja (kancer, autoimunske bolesti, Parkinsonova i Alchajmerova bolest, itd.) Međutim, tek u poslednjih desetak godina intenzivno se istražuje uticaj smanjenog unosa hrane na procese oporavka nakon povrede. Dosadašnja istraživanja na ovom polju su pokazala da restrikcija hrane u trajanju od nekoliko meseci pre povrede CNS-a ima neuroprotektivno dejstvo i promoviše funkcionalni oporavak u nekoliko različitih modela povrede... Traumatic brain injury (TBI) represents a brain tissue injury caused by mechanical head injury. TBI is one of the leading causes of death and disability in the world human population, up to 45 years of age. Consequences of brain injury depend on the location and amount of brain tissue damage, and can range from mild motor and cognitive impairment, to severe forms of disability and death. Traumatic brain injury leads to impairment of blood-brain barrier, resulting in a precisely defined sequence of events in injured CNS tissue. Two main phases could be distinguished: acute phase, which is called the primary injury that occurs by direct action of mechanical forces on the brain tissue and occurs at the time of injury. The events that followed thereafter are called the secondary injury. Secondary injury occurs as a result of the initial damage, and includes the processes that lead to further tissue damage in the days and weeks following injury. These are primarily inflammatory processes that lead to the death of neurons that initially were not affected by mechanical injury. It is believed that the neuronal cell death caused by secondary injury is far greater than the one caused by primary injury. The fact that most of the processes within the secondary injury occur relatively late (hours and days following injury) makes them subject to various therapeutic interventions. For decades, it is known that food restriction has a beneficial effect on the entire organism by delaying age-dependent physiological changes and reducing the incidence of various diseases (cancer, autoimmune disease, Parkinson's and Alzheimer's, etc). However, only in the last ten years has been to investigate the influence reduced food intake in the recovery process following injury. Previous research in this field has shown that several months long food restriction prior to CNS injury has neuroprotective effects and promotes functional recovery in several different models of injury... Univerzitet u Beogradu Biološki fakultet Kanazir, Selma Nedeljković, Nadežda Pešić, Vesna, 1964- Ruždijić, Sabera Perović, Milka 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=39 https://fedorabg.bg.ac.rs/fedora/get/o:2348/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41539855 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:40 2012-11-22T00:00:00Z 1

Uticaj delimičnog isušivanja korenova na ekspresiju NCED, TAO1 i EIL1 gena i rastenje divljeg tipa i flacca mutanta paradajza (Lycopersicon esculentum Mill.) The effect of partial root-zone drying on expression of NCED, TAO1 and EIL1 genes and growth in tomato wild-type and flacca mutant (Lycopersicon esculentum Mill.) Milosavljević, Ana Z., 1981- delimiĉno isušivanje korenova, regulisani deficit irigacije, paradajz, vodni reţim, ABA, joni, NCED, TAO1, EIL1 Tomato, partial root-zone drying, regulated deficit irrigation, water regime, ABA content, ions, NCED, TAO1, EIL1 Datum odbrane: 25.07.2012. Cilj ovog istraţivanja je bio karakterizacija fizioloških procesa koji su u osnovi regulacije rastenja i razvića biljaka paradajza pod dejstvom delimiĉnog isušivanja korenova (Partial root-zone drying -PRD), ali i regulisanog deficita navodnjavanja (Regulated deficit irrigation - RDI). Cilj je bio i da se u ova ispitivanja ukljuĉe i molekularna istraţivanja, koja bi, uz analizu procesa rastenja i drugih fizioloških procesa (vodnog reţima, razmene gasova, akumulacije i distribucije stres hormona ABA, kao i usvajanja i distribucije jona), znaĉajno doprinela razumevanju PRD i RDI efekata na paradajz. Zato je praćena ekspresija gena ukljuĉenih u biosintetski put ABA (TAO1 i NCED1) i transdukciju signala etilena (EIL1). Eksperimentalni model u ovim istraţivanjima je bio paradajz (Lycopersicon esculentum Mill.), kao kultura koja ima znaĉajne potrebe za vodom i kod koje suša moţe da izazove znaĉajne efekte na rastenje i razviće. Odabrani su divlji tip (WT), sorta Ailsa Craig, i mutant flacca koji se odlikuje smanjenom sintezom hormona ABA. Biljke paradajza divljeg tipa i mutanta flacca su nakon proklijavanja presaĊene u posebno dizajnirane saksije, koje su podeljene na dve polovine plastiĉnom ploĉom, ĉime je omogućeno razdvajanje korenovog sistema u dva hidrauliĉno izolovana kompartmenta. Biljke su gajene u komercijalnom supstratu (Klasmann Potground H) u uslovima fitotronske komore (temperatura dan/noć 26/17 oC, relativna vlaţnost vazduha 60%, osvetljenost (PAR) 250 μmolm-2s-1 i duţina fotoperioda od 14 h). Koliĉina vode u supstratu je merena pomoću TDR proba (Time domain reflectometer, TRASE, Soil Moisture Equipment Corp., USA). Primenjivana su tri razliĉita tretmana zalivanja. Optimalno navodnjavanje (Full irrigation - FI) - supstrat u celoj rizosferi je svaki dan zalivan do optimalnog vodnog kapaciteta, odnosno, sadrţaja vode u supstratu od 36%. Delimiĉno isušivanje korenovog sistema (PRD) - supstrat u polovini korenovog sistema je zalivan do optimalnog vodnog kapaciteta, dok u drugoj polovini nije zalivan sve dok se sadrţaj vode u supstratu nije spustio na 18- 20%, kada je vršena inverzija strana zalivanja. Regulisani deficit navodnjavanja (RDI) - biljke su zalivane do vrednosti vode u supstratu od 18%. Vodni potencijal listova i otvorenost stoma su mereni u danu PRD okreta (promene strane zalivanja korena)... The aim of presented PhD thesis was to investigate the physiological mechanisms that are in the base of tomato growth and development under partial root-zone drying (PRD) and regulated deficit irrigation (RDI). Investigations included plant growth, water regime, gas exchange, abscisic acid (ABA) content in the leaves of tomato and ions content in different tomato plant organs. The aim of presented PhD thesis was, also, to assess the expression of TAO1, NCED and EIL1 genes in the leaves of tomato under drought treatments of PRD and RDI. The investigated genes are involved in the biosynthesis and signaling pathways of abscisic acid (ABA) and ethylene as key hormones in the reactions of plants to drought. Experiments were done with tomato plants (Lycopersicon esculentum Mill.), wild type (Ailsa Craig) and flacca mutant. Tomato was chosen because of its significant needs for water and because drought may have significant effects on its growth and development. Tomato mutant flacca, which is chosen for investigation, is defective in the last step of ABA biosynthesis. As a consequence, the endogenous level of ABA in flacca tissues is significantly lower than in wild type. Tomato plants wild type (WT) and flacca mutant were raised from seed and transplanted into 10 L pots (one plant per pot) filled with commercial compost (Klasmann Potground H) in a growth chamber (photoperiod was 14 h; light intensity at plant level 250 μmolm-2s-1, temperature 26/17 oC and relative humidity 60%). For PRD experiments the pots were specially designed in such a way that they were separated with plastic sheets into two equally sized compartments. Washed roots of the seedlings were divided into approximate halves and repotted into these two hydraulically separated compartments. The volumetric soil water content (θ) of both compartments of each pot was measured daily using TDR probes (time domain reflectometer, TRASE, Soil Moisture Equipment Corp., USA After transplantation, plants were subjected to following irrigation treatments: full irrigation (FI), in which the whole root system was irrigated to full substrate holding capacity (θ of 36%); ) partial root-zone drying (PRD), where one half of the root was irrigated to reach θ of 36% while the other half was allowed to dry, and the irrigation was shifted when θ of the dry side had decreased to 18-20%. deficit irrigation (RDI), in which water was evenly applied to the whole root system to rich θ of 18%. Leaf water potential and stomatal conductance were measured in day when PRD shift occurred... Univerzitet u Beogradu Biološki fakultet Stikić, Radmila Sabovljević, Aneta Subotić, Angelina 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=40 https://fedorabg.bg.ac.rs/fedora/get/o:2350/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41538063 sr Autorstvo-Nekomercijalno 3.0 Srbija (CC BY-NC 3.0)

oai:eteze.bg.ac.rs:41 2013-09-19T00:00:00Z 1

Metabolička raznovrsnost bakterija izolovanih iz površinskog rečnog sedimenta pod uticajem petrohemijskih efluenata: Pseudomonas sp. tn301 kao proizvođač polihidroksialkanoata Metabolic varsality of bacteria isolated from surgace river sediment influenced by petrochemical effluentes: the case of Pseudomonassp. TN301 as polyhydroxyalkanoate producer Narančić, Tanja M., 1979- Monoaromatična jedinjenja, poliaromatična jedinjenja, biodegradacija, bioremedijacija, teški metali, polifosfati, egzopolisaharidi, polihidroksibutirat, polihidroksialkanoat, Pseudomonas Monoaromatic compounds, polyaromatic hydrocarbons, biodegradation, , heavy metals, bioremediation, polyphosphates, exopolysaccharides, polyhydroxybutyrate, polyhydroxyalkanoate, Pseudomonas Datum odbrane: 06.07.2012. Mono- i poliaromatična jedinjenja predstavljaju široko rasprostranjene zagađivače životne sredine. Ova jedinjenja veoma dugo opstaju u datoj sredini, a mnoga od njih imaju i toksična, kancerogena i mutagena svojstva. Sredine zagađene aromatičnim jedinjenjima su najčešće kontaminirane i teškim metalima, a odlikuju se i neravnotežnim odnosom esencijalnih nutrijenata. Sa druge strane, ovakve sredine su dobar izvor bakterija sa sposobnošću preživljavanja u izuzetno teškim uslovima. Cilj ovog rada je bila izolacija robustnih bakterija sa potencijalnom biotehnološkom aplikacijom iz sedimenata koji su pod uticajem petrohemijskih efluenata. Upotrebom dve različite strategije izolovanja, toplotnog pretretmana i medijuma za rast i sporulaciju Actinobacteria, i predobogaćivanja uzoraka naftalenom u kombinaciji sa odabirom brzo rastućih bakterija sa sposobnošću rasta na naftalenu kao jedinom izvoru ugljenika i energije izolovane su 34 Gram-pozitivne i 4 Gram-negativne bakterije. Izolati sa sposobnošću degradacije od 9 do 15 najčešćih aromatičnih polutanata poput benzena, bifenila i naftalena pripadali su rodovima Bacillus, Arthrobacter, Rhodococcus, Gordonia, Streptomyces, Staphylococcus, Actinobacteria, Sinorhizobium i Pseudomonas. Rhodococcus sp. TN105, Gordonia sp. TN103 i Arthrobacter sp. TN221 su identifikovani kao novi sojevi. Od 11 izolata sa sposobnošću rasta u prisustvu bar jednog od testiranih teških metala (živa, kadmijum, nikl) u 100 mM koncentracijama, 8 je imalo sposobnost degradacije 15 različitih aromatičnih jedinjenja. Rezistenciju na bar jedan od testiranih antibiotika pokazalo je 60% izolata. Međutim, nije primećena visoka učestanost multirezistencije na antibiotike. Trećina izolata je imala sposobnost da akumulira bar jedan od biopolimera. Dvanaest izolata, uglavnom pripadnika rodova Bacillus i Arthrobacter su akumulirali polifosfate, 3 Bacillus sp. izolata su akumulirala polihidroksibutirat (PHB), Pseudomonas sp. TN301 je akumulirao polihidroksialkanoate srednje duzine niza (mcl-PHA), dok su 4 Grampozitivna izolata akumulirala egzopolisaharide. U ovom radu je po prvi put pokazana sposobnost pripadnika roda Bacillus da konvertuju toluen u PHB. Pseudomonas sp. TN301 se istakao zbog svoje sposobnosti da akumulira mcl-PHA do 22% suve ćelijske mase iz poliaromatičnog jedinjenja naftalena. Razvijen je metod za dodavanje izrazito hidrofobnih poliaromatičnih jedinjenja u kultivacioni medijum. Najveća masa i najviši nivo akumuliranog mcl-PHA postignuti su dodavanjem sintetičkog surfaktanta Tweena 80 (0.5 g l-1). Pokazano je da Pseudomonas sp. TN301 ima sposobnost akumulacije mcl-PHA iz širokog opsega poli- i monoaromatičnih jedinjenja, kao i njihovih smeša. Ovaj rad predstavlja prvu sveobuhvatnu studiju metabolički raznovrsnih, u prvom redu Gram-pozitivnih bakterija sa velikim aplikacionim potencijalom u procesu bioremedijacije sredina zagađenih mešovitim polutantima, ali i sa drugim biotehnološkim aplikacijama kao sto je konverzija otpadnog materijala u biopolimere. U ovom radu je po prvi put pokazana sposobnost bakterijskog soja da konvertuje različita poliaromatična jedinjenja i njihove smeše u biodegradabilni polimer (mcl- PHA). S obzirom na to da ima odlike biodegradabilnog termoelastomera, mcl-PHAsve više dobija na važnosti, pa je izolacija novih sojeva sa sposobnošću njegove produkcije od izuzetnog značaja. Mono- and polyaromatic compounds are among the most prevalent and persistent pollutants in the environment. They have been reported as toxic, carcinogenic and mutagenic. Contaminated sites usually contain complex mixture of aromatic compounds and heavy metals, and are characterized by essential nutrients imbalance. On the other hand, polluted sites proved to be valuable sources of bacteria capable of surviving in these harsh environments. The aim of this study was to obtain robust bacteria with potential biotechnological application from the river sediments affected by the proximity of a petrochemical industrial site. Using two different isolation strategies, heat pretreatment and media for growth and sporulation of Actinobacteria and naphthalene enrichment combined with the selection of fast growing bacteria capable of using naphthalene as the sole source of carbon and energy, 34 Gram-positive and 4 Gram-negative bacterial strains were isolated. Isolates that were able to use 9 or more common aromatic pollutants, such as benzene, biphenyl, naphthalene etc. as a sole source of carbon and energy included members of Bacillus, Arthrobacter, Rhodococcus, Gordonia, Streptomyces, Staphylococcus, Actinobacteria, Sinorhizobium, and Pseudomonas genus. Rhodococcus sp. TN105, Gordonia sp. TN103 and Arthrobacter sp. TN221 were identified as novel strains. Out of 11 isolates able to grow in the presence of one or more metals (mercury, cadmium, nickel) at high concentration (100 mM), eight could degrade 15 different aromatic compounds. Antibiotic resistance to at least one of the tested antibiotics was found among 60% of the isolates. However, high incidence of multiresistance was not observed. One third of the isolates could accumulate at least one biopolymer. Twelve isolates (mainly Bacillus sp. and Arthrobacter sp.) accumulated polyphosphate, three Bacillus sp. accumulated polyhydroxybutyrate (PHB), and Pseudomonas sp. TN301 accumulated medium chain length polyhydroxyalkanoate (mcl-PHA), while four Gram-positive isolates could accumulate exopolysaccharides. This study is the first report of a Bacillus strain capable of converting toluene to PHB. Pseudomonas sp. TN301 was distinguished by its ability to accumulate mcl-PHA up to 22% of cell dry weight from the naphthalene. A method of supplying highly hydrophobic polyaromatic hydrocarbons to a culture medium was developed. The best biomass and mcl-PHA yields were achieved with the addition of synthetic surfactant Tween 80 (0.5 g l-1). It was shown that Pseudomonas sp. TN301 can accumulate mcl-PHA from a wide range of poly- and monoaromatic hydrocarbons, and mixtures thereof. This is the first comprehensive study on the metabolically diverse, primarily Grampositive bacteria with great application potential for mixed pollution bioremediation studies, as well as in other biotechnological applications such as waste conversion to biopolymers. Also, this is the first report of the ability of a bacterial strain to convert a range of polyaromatic hydrocarbon compounds to the biodegradable polymer (mcl- PHA). Mcl-PHA is gaining importance as a promising biodegradable thermoelastomer and therefore isolation of new producing strains is highly significant. Univerzitet u Beogradu Biološki fakultet Nikodinović-Runić, Jasmina Fira, Đorđe, 1959- Fira, Đorđe, 1959- Vasiljević, Branka 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=41 https://fedorabg.bg.ac.rs/fedora/get/o:2400/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41542415 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:42 2012-12-06T00:00:00Z 1

Uloga humoralnog imunskog odgovora u etiopatogenezi amiotrofične lateralne skleroze The role of humoral immune response in the aetiopathogenesis of amyotrophic lateral sclerosis Milošević, Milena M., 1977- amiotrofična lateralna skleroza, imunoglobulin G, kalcijumova homeostaza, endozomi, lizozomi, mobilnost vezikula, astrociti amyotrophic lateral sclerosis, immunoglobulin G, calcium homeostasis, endosomes, lysosomes, vesicle mobility, astrocytes Datum odbrane: 28.09.2012. Amiotrofična lateralna skleroza (ALS) je fatalna neurodegenerativna bolest sa početkom u adultnom dobu koja se karakteriše progresivnim gubitkom gornjih i donjih motoneurona, što dovodi do atrofije muskulature, mišićne paralize i smrti usled slabosti respiratorne muskulature. Oko 5-10% ALS slučajeva su sa familijarnom istorijom bolesti (fALS), dok su preostali slučajevi sporadični (sALS) sa nepoznatim uzrokom bolesti. Cilj ove disertacije bio je da proceni efekat imunoglobulina G (IgG) izolovanog iz sALS bolesnika (ALS IgG) na homeostazu kalcijuma i mobilnost endozoma/lizozoma kod pacovskih kortikalnih astrocita u kulturi. ALS IgG (0.1 mg/ml) poreklom od 7 ALS pacijenata, za razliku od IgG iz 3 kontrolne osobe, izazvao je prolazne promene unutarćelijske koncentracije kalcijuma (Ca2+-talas) u astrocitima. Povećana aktivnost kalcijuma detektovana je kod oko polovine astrocita nakon tretmana sa ALS IgG, bez obzira na prisustvo vanćelijskog kalcijuma (47,5 ± 12,9 %, 2 mM Ca2+ naspram 48,2 ± 13,6 %, 0 mM Ca2+). U prisustvu vanćelijskog kalcijuma, maksimalna vrednost promene dostignuta je ~3x brže (19,7 ± 2,8 s, 2 mM Ca2+ naspram 56,3 ± 6,8 s, 0 mM Ca2+) i ukupno povećanje kalcijuma (površina pod Ca2+-talasom) bilo je ~1.7x veće (26,0 ± 1,6 F/F0 *s, 2 mM Ca2+ naspram 15,6 ± 1.1 F/F0 *s, 0 mM Ca2+), ali vanćelijski kalcijum nije uticao na maksimum amplitude kalcijumovog talasa. Primena farmakoloških inhibitora otkrila je da je aktivacija inozotol 1,4,5-trifosfatnog (IP3), za razliku od rianodinskog receptora neophodna i dovoljna da inicira povećanu aktivnost, a ulazak kalcijuma kroz TRPC kanale produžava odgovor. Inhibicija fosfolipaze C (PLC) umanjuje, dok inhibicija fosfatidilinozitol-3-kinaze (PI3K) u potpunosti sprečava tipičan ALS IgG-izazvan kalcijumski odgovor. Populacija vezikula obeleženih lizotrekerom koji boji endozome i lizozome, sastojala se od stacionarnih vezikula (6,1%) sa prosečnom brzinom koja nije prelazila 67 nm/s i mobilnih vezikula (93.9%) čija je ukupna dužina putanje (TL) pređene za 15 s iznosila u proseku 3,03±0,01 μm. ALS IgG (0.1 mg/ml) poreklom iz 12 od 13 ALS bolesnika povećao je TL mobilnih vezikula za ~24% i maksimalni pomeraj (MD) za ~26% tokom praćenih 4 min, za razliku od kontrolnih IgG (poreklom od 4 osobe) koji nisu uticali na mobilnost vezikula. ALS IgG-izazvano povećanje mobilnosti bilo je manje izraženo u rastvoru bez Ca2+, što ukazuje da su promene u homeostazi kalcijuma uključene u proces kojim ALS IgG povećava mobilnost vezikula. Interesantno, ALS IgG kao i ATP (1 mM) nisu uticali na oslobađanje sadržaja vezikula, što znači da je brza i kompletna egzocitoza malo verovatan događaj kod astrocita u kulturi u našim eksperimentalnim uslovima. Sumarno, ALS IgG utiče na kalcijumovu homeostazu astrocita preko IP3-posredovanog oslobađanja kalcijuma iz endoplazmatičnog retikuluma i ulaska kalcijuma kroz TRPC kanale, uz aktivaciju PI3K uzvodno od PLC. ALS IgG povećavaju mobilnost endozoma i lizozoma, a ovaj efekat delimično zavisi od vanćelijskog kalcijuma. Ova studija je otkrila molekulske mehanizme kojima astrociti postaju meta humoralnog imunskog odgovora u ALS, što može da doprinese etiopatogenezi bolesti. Amyotrophic lateral sclerosis (ALS) is an adult onset fatal neurodegenerative disease characterized mainly by the progressive loss of upper and lower motor neurons resulting in wasting, paresis and death from respiratory failure. Approximately 5-10% of ALS cases are familial (fALS), while the rest are sporadic (sALS) with unknown cause of disease. The objective of this dissertation was to evaluate the effect of immunoglobulin G (IgG) isolated from sALS patients (ALS IgG) on calcium homeostasis and mobility of endosomes/lysosomes in cultured rat cortical astrocytes. ALS IgG (0.1 mg/ml) from 7 ALS patients, but not IgG from 3 control individuals evoked calcium transients (Ca2+-waves) in astrocytes. About half of the tested astrocytes responded with elevated calcium activity regardless of the presence of extracellular calcium (47.5 ± 12.9 %, 2 mM Ca2+ vs. 48.2 ± 13.6 %, 0 mM Ca2+). In presence of extracellular calcium, the peak amplitude developed ~3x faster (19.7 ± 2.8 s, 2 mM Ca2+ vs. 56.3 ± 6.8 s, 0 mM Ca2+) and the overall magnitude of calcium rise (area under the Ca2+-wave) was ~1.7x larger (26.0 ± 1.6 F/F0 *s, 2 mM Ca2+ vs. 15.6 ± 1.1 F/F0 *s, 0 mM Ca2+), while the peak amplitude itself was not affected. Application of pharmacological inhibitors revealed that activation of inositol 1,4,5- triphosphate (IP3), but not of ryanodine receptors is necessary and sufficient to initiate elevated activity, while the influx of extracellular calcium through TRPC channels prolongs the responses. Inhibition of phospholipase C (PLC) diminishes, while the inhibition of phosphatidilinositol-3-kinase (PI3K) completely prevents typical ALS IgG evoked calcium response. The population of vesicles labeled with lysotracker that mainly stains endosomes and lysosomes, consisted of non-mobile (6.1%) vesicles with the average speed of <67 nm/s and mobile vesicles (93.9%) with total track length (TL) in 15 s averaging at 3.03±0.01 μm. ALS IgG (0.1 mg/ml) from 12 of 13 patients increased the TL of mobile vesicles by ~24% and the maximal displacement (MD) by ~26% within 4 min, while IgG from control group (n=4) did not alter the vesicle mobility. The mobility enhancement by ALS IgG was less pronounced in Ca2+-free extracellular solution, indicating that ALS IgG vesicle mobility enhancement involves changes in Ca2+ homeostasis. Interestingly, neither ALS IgG nor ATP (1 mM) triggered the release of vesicular cargo, making rapid and complete exocytosis unlikely in cultured astrocytes in our experimental conditions. In conclusion, ALS IgG affect calcium homeostatic system in astrocytes by IP3 mediated calcium release from the endoplasmic reticulum and entry of extracellular calcium through TRPC channels, with the activation of PI3K upstream of PLC. ALS IgG enhance the mobility of endosomes and lysosomes, and this effect is partialy dependent on extracellular calcium. This study revealed the molecular mechanisms by which astrocytes become targeted cells for humoral immune response in ALS that could contribute to the aetiopathogenesis of the disease. Univerzitet u Beogradu Biološki fakultet Anđus, Pavle, 1958- Stenovec, Matjaž Stević, Zorica, 1959- Božić, Biljana, 1975- Miljković, Đorđe 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=42 https://fedorabg.bg.ac.rs/fedora/get/o:2411/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41534223 sr Autorstvo-Nekomercijalno 3.0 Srbija (CC BY-NC 3.0)

oai:eteze.bg.ac.rs:43 2024-07-25T00:00:00Z 1

Kаrаktеrizаciја prоcеsа prоgrаmirаnе ćеliјskе smrti i sеnеscеnciје u listоvimа Nicotiana tabacum L. in vitro Characterisation of programmed cell death and senescence in leaves of Nicotiana tabacum L. in vitro Uzelac, Branka, 1973- аntiоksidаtivni еnzimi, citоkinini, Nicotiana tabacum L., prоgrаmirаnа ćеliјskа smrt, qRT-PCR, rеmоbilizаciја аzоtа, sеnеscеnciја listа, TUNEL rеаkciја, ultrаstrukturа antioxidative enzymes, cytokinins, leaf senescence, Nicotiana tabacum L., nitrogen remobilization, programmed cell death, qRT-PCR, TUNEL assay, ultrastructure Datum odbrane: 04.09.2012. Sеnеscеnciја listа prеdstаvlја kоmplеksnu, gеnеtički kоntrоlisаnu pоslеdnju fаzu оntоgеnеzе listа kоја rеzultirа kооrdinisаnоm rаzgrаdnjоm mаkrоmоlеkulа i mоbilizаciјоm njеgоvih kоmpоnеnti u drugе dеlоvе bilјkе. Nа ćеliјskоm nivоu, оnа оbuhvаtа prоmеnе strukturе, mеtаbоlizmа i gеnskе еksprеsiје kоје dоvоdе dо smrti, čiјi sе tip оznаčаvа kао prоgrаmirаnа ćеliјskа smrt (PCD). Kао еkspеrimеntаlni mоdеl u оvоm rаdu kоrišćеnе su in vitro gајеnе bilјkе duvаnа (Nicotiana tabacum L.) kоје оbеzbеđuјu sеt listоvа u kојimа pоstојi grаdаciја sеnеscеnciје. Istrаživаnjе је оbuhvаtilо citоhistоlоšku i imunоhistоhеmiјsku аnаlizu dinаmikе strukturnih prоmеnа mеzоfilа listоvа, kао i ispitivаnjе mеtаbоličkih, biоhеmiјskih i mоlеkulаrnih prоcеsа tоkоm sеnеscеnciје listа. Utvrđеn је rеdоslеd dеgеnеrаtivnih prоmеnа u strukturi ćеliја tоkоm fiziоlоškоg stаrеnjа listоvа. U sеnеscеntnim listоvimа dеtеktоvаni su tipični simptоmi prоgrаmirаnе ćеliјskе smrti, kоја pо svојim mоrfоlоškim оdlikаmа оdgоvаrа аutоfаgnој ćеliјskој smrti, i pоkаzаnо dа intеrnuklеоzоmаlnа frаgmеntаciја DNK prеthоdi ultrаstrukturnim prоmеnаmа kао štо su dеgrаdаciја hlоrоplаstа i kоndеnzаciја hrоmаtinа. Sаdržај hlоrоfilа i citоsоlnih prоtеinа idеntifikоvаni su kао pоuzdаni biоmаrkеri stеpеnа sеnеscеnciје listоvа. Hеmiјskоm аnаlizоm еndоgеnih rеgulаtоrа rаstеnjа idеntifikоvаnо је i kvаntifikоvаnо višе оd 20 rаzličitih citоkininа i pоkаzаnо dа је nаprеdоvаnjе sеnеscеnciје u kоrеlаciјi sа оpаdаnjеm sаdržаја ukupnih citоkininа, kао i sа smаnjеnjеm nivоа citоkininа trans-zеаtinskоg tipа. Таkоđе је uоčеnа јаsnа kоrеlаciја izmеđu smаnjеnjа nivоа еndоgеnе IAA, оdnоsnо ABA i nаprеdоvаnjа sеnеscеnciје. Imunоhistоhеmiјskоm аnаlizоm mеzоfilа listоvа bilјаkа trеtirаnih citоkininimа pоkаzаnо је dа visоkе dоzе citоkininа BА ubrzаvајu sеnеscеnciјu, čimе indukuјu prоgrаmirаnu smrt ćеliја. Аnаlizа аktivnоsti pојеdinih еnzimskih kоmpоnеnti аntiоksidаtivnоg sistеmа pоkаzаlа је znаčајnе prоmеnе u аntiоksidаtivnоm stаtusu listоvа tоkоm fiziоlоškоg stаrеnjа. Nаprеdоvаnjе sеnеscеnciје је u јаsnој kоrеlаciјi sа smаnjеnjеm аktivnоsti CAT i pоvеćаnjеm ukupnе аktivnоsti POD. Primаrnu аntiоksidаtivnu zаštitu tоkоm stаrеnjа оbеzbеđuјu SOD, а u prоcеs оdbrаnе оd štеtnоg dејstvа ROS u iniciјаlnој fаzi sеnеscеnciје uklјučuјu sе POD. Моlеkulаrnа аnаlizа sеnеscеnciје pоkаzаlа је аktivаciјu gеnа kојi kоdirајu еnzimе uklјučеnе u kоnvеrziјu i rеmоbilizаciјu prоdukаtа rаzlаgаnjа u sеnеscеntnim listоvimа. qRT-PCR mеtоdоm pоkаzаnа је indukciја еksprеsiје gеnа kојi kоdirајu cistеin prоtеаzе оdgоvоrnе zа rеmоbilizаciјu аminоkisеlinа, kао i cistеin prоtеаzu iz grupе mеtаkаspаzа uklјučеnu u kоntrоlu ćеliјskе smrti. Indukciја еksprеsiје Gln1-3 i GDH2, SAG-gеnа uklјučеnih u mоbilizаciјu аzоtа u sеnеscеntnim listоvimа, nаpоrеdо sа pаdоm еksprеsiје GS2 ukаzаlа је dа sе аsimilаciја аmоniјumа tоkоm sеnеscеnciје pоstеpеnо prеmеštа iz hlоrоplаstа u citоsоl mеzоfilnih ćеliја. Leaf senescence constitutes the final stage of leaf development that results in the coordinated degradation of macromolcules and the subsequent nutrient relocation to other plant parts. Leaf senescence involves an integrated action at the cellular, tissue, organ and organism levels under the control of a highly regulated genetic program. During senescence, leaf cells undergo orderly changes in cell structure, metabolism and gene expression leading to cell death, recognized as a form of programmed cell death (PCD). In vitro grown Nicotiana tabacum L. has been chosen as a model plant system, since a single plant provides a large set of leaves in which there is a gradation of senescence. The dynamics of ultrastructural changes in leaf mesophyll cells, as well as metabolic, biochemical and molecular changes during leaf senescence were investigated. We determined the time sequence of senescence-related events in mesophyll cells during physiological ageing of leaves. Typical symptoms of autophagic PCD were detected in senescing leaves using cytological analysis and TUNEL assay. We showed that PCD-specific nuclear DNA fragmentation occurs during natural tobacco leaf senescence but that it starts early in leaf development, thus preceeding ultrastructural changes such as chloroplast degradation and chromatin condensation. Chlorophyll and soluble protein content were identified as reliable biomarkers for estimating the relative age of a particular leaf along the main plant axis. Using HPLC/MS more than 20 different cytokinins were identified and quantified in tobacco leaves. The correlation of senescence with decline in total cytokinin content and the levels of trans-Z was found. The progression of leaf senescence correlated with a gradual decrease in endogenous levels of both IAA and ABA. Immunohistological analysis showed that high levels of cytokinin benzyladenine accelerate senescence thus inducing PCD. The activities of different antioxidative enzymes were analyzed during physiological ageing of leaves. Progression of senescence is correlated with decrease in CAT activity and a concomitant increase in POD activity. Primary antioxidative protection in the course of ageing is provided by SOD, whereas POD are implicated in defense against detrimental ROS action in an initial phase of senescence. Molecular analysis of leaf senescence has revealed activation of genes encoding enzymes involved in conversion and remobilization of degradation products in senescing leaves. Quantitative RT-PCR showed that the expression of cysteine proteases responsible for amino acid remobilization, typically associated with leaf senescence and not found in other forms of PCD, was induced in senescent leaves. Induced expression of SAGs involved in nitrogen mobilization in senescing leaves, Gln1-3 и GDH2, contiguous with decrease in GS2 expression indicated that, during senescence, ammonia assimilation is progressively shifted from the chloroplasts to the cytosol of leaf mesophyll cells. Univerzitet u Beogradu Biološki fakultet Budimir, Snežana, 1958- Janošević, Dušica, 1962- Simonović, Ana, 1969- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=43 https://fedorabg.bg.ac.rs/fedora/get/o:2416/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41541135 sr Autorstvo 3.0 Srbija (CC BY 3.0)

oai:eteze.bg.ac.rs:44 2013-09-30T00:00:00Z 1

Fiziološki i biohemijski aspekti regeneracije košutice (Fritillaria meleagris L.) in vitro Physiological and biochemical aspects of regeneration snake's head fritillary (Fritillaria meleargis L.) in vitro Petrić, Marija P. 1980- Fritillaria meleagris, morfogeneza in vitro, dormancija lukovica, organogeneza, oksidativni stres, somatska embriogeneza, antioksidativni enzimi, esteraze, arabinogalaktanski proteini Fritillaria meleagris, morphogenesis in vitro, bulb dormancy, organogenesis, oxidative stress, somatic embryogenesis, antioxidative enzymes, esterases, arabinogalactan proteins Datum odbrane: 10.07.2012. Proučavana je in vitro regeneracijia košutice (Fritillaria meleagris), višegodišnje lukovičaste geofite. Indukcija morfogeneze in vitro košutice postignuta je u kulturi zrelih zigotskih embriona, segmenata lukovica kao i bazalnih delova listova in vitro formiranih lukovica. U kulturi zrelih zigotskih embriona regeneracija biljaka je postignuta procesom somatske embriogeneze i organogeneze u isto vreme i na istom eksplalntatu na hranljivoj podlozi bez regulatora rastenja ili hranljivoj podlozi obogaćenoj sa TDZ. U kulturi segmenata in vitro formiranih lukovica indukcija morfogeneze postignuta je na hranljivoj podlozi sa 2,4-D ili TDZ na svetlosti ili u mraku. Regeneracija biljaka je bila postignuta na obe hranljive podloge putem somatske embriogeneze i organogeneze, s tim da je regeneracija putem organogeneze bila uspešnija na hranljivoj podlozi obogaćenoj sa TDZ. U kulturi bazalnih delova listova indukovana je somatska embriogeneza na hranljivim podlogama sa 2,4-D, KIN ili 2,4-D i KIN. Anatomska istraživanja su pokazala da je somatska embriogeneza direktna, a somatski embrioni imaju višećelijsko poreklo i nastaju od epidermalnih i subepidermalnih slojeva ćelija bazalnih delova lista. Ispitan je uticaj niskih temperatura (15 i 4 °C), povećane koncentracije saharoze u hranljivoj podlozi kao i predtretman sa GA3 na rastenje, razviće i prevazilaženje dormancije in vitro formiranih lukovica košutice. Pokazano je da predhodno gajenje lukovica na sniženim temperaturama i hranljivoj podlozi sa 4,5 % saharoze pozitivno utiče na rastenje i umnožavanje lukovica. Pored toga, predtretman rastvorom GA3 pre izlaganja lukovica niskoj temperaturi (4 °C) dovodi do stimulacije umnožavanja i klijanja lukovica. Izlaganjem in vitro formiranih lukovica košutice niskoj temperaturi dolazi do promena u sadržaju šećera (saharoze, glukoze i fruktoze), fotosintetičkih pigmenata i poliola. Ispitana je aktivnost antioksidativnh enzima (SOD, CAT, GR i POX) tokom prevazilaženja dormancije lukovica gajenjem na niskoj temperaturi. Analize su pokazale da enzimi antioksidativnog stresa aktivno učestvuju u procesima prekidanja dormancije in vitro formiranih lukovica košutice, kao i aklimatizacije lukovica na ex vitro uslove. Enzimi antioksidativne zaštite su aktivni i tokom indukcije morfogeneze košutice u kulturi segmenata lukovica, a njihova aktivnost zavisi od sastava hranljive podloge i predtretmana kome su lukovice prethodno izložene. Zimogramskom detekcijom esteraza tokom indukcije morfogeneze in vitro u kulturi segmenata lukovica utvrđeno je prisustvo 6 izoformi i njihova aktivnost kao i zastupljenost pojedinih izoformi zavise takođe od predtretmana na kojima su lukovice predhodno gajene kao i od regulatora rastenja u hranljivoj podlozi. Praćena je promena sadržaja arabinogalaktanskih proteina (AGP) u eksplantatima tokom indukcije morfogeneze in vitro u kulturi bazalnih delova listova i segmenata lukovica na dve hranljive podloge obogaćene sa 2,4-D i KIN ili TDZ. Koncentracija AGP u eksplantatima se povećava već posle 7 dana gajenja bazalnih delova listova odnosno posle 21 dana gajenja segmenata lukovica na hranljivim podlogama sa regulatorima rastenja. Koncentracija AGP je veća u bazalnim segmentima lista gajenim na hranljivoj podlozi sa 2,4-D i KIN nego na hranljivoj podlozi sa TDZ. Analizom profila AGP dobijenog ukrštenom elektroforezom pokazano je prisustvo samo jednog tipa AGP tokom indukcije morfogeneze in vitro. We have investigated in vitro regeneration of snake’head fritillary (Fritillaria meleagris L.), a perennial bulbous geophyte. The induction of morphogenesis in vitro of snake’head fritillary was achieved in mature zygotic embryo culture, scale segment and leaf base culture of in vitro formed bulbs. Plant regeneration via somatic embryogenesis and organogenesis was obtained in mature zygotic embryo culture on a growth regulator-free medium or on medium supplemented with TDZ. The induction of morphogenesis in vitro was achieved in scale segment culture of the in vitro formed bulbs on media supplemented with 2,4-D or TDZ, grown either on light or in darkness, with more efficient regeneration on media supplementned with TDZ. Somatic embryogenesis was induced in leaf base culture of the in vitro formed plants on media with 2,4-D, KIN or 2,4-D and KIN. Anatomical studies revealed that the somatic embryogenesis was direct, with somatic embryos of multicellular origin formed from epidermal and subepidermal leaf base cells . The effect of low temperature (4 and 15 °C), higher concentration of sucrose in the nutritional media and GA3 pretreatment on growth, differentiation and dormancy breaking of the in vitro formed bulbs was investigated. It was shown that pre-cultivation of the in vitro regenerated bulbs at lower temperatures and higher concentration of sucrose in the nutrition media (4,5 %) have stimulatory effect on growth and multiplication of the bulbs. Also, GA3 pretretment followed by cultivation at low temperature (4 °C) had a stimulatory effect on multiplication and germination of the bulbs. Cultivation at low temperature breaks dormancy of the bulbs and causees changes in the sugar content (sucrose, glucose and fructose), photosinthetic pigments and poliols. Activity of antioxidative enzymes (SOD, CAT, GR i POX) during dormancy breaking was investigated. It was shown that these enyzmes are actively involved in dormancy breaking of the in vitro formed bulbs, and in the process of acclimatization of the bulbs to ex vitro conditions. Antioxidative enzymes were active during the induction of morphogenesis in vitro in bulb segment culture and their activity depended on the nutritional media and the pretreatment to which the bulbs were exposed. During morphogenesis in vitro in the scale segment culture of snake’s head fritillary, up to 6 esterase isoforms have been detected, depending on the pretreatment and media composition. The content of arabinogalactan proteins (AGPs) in explants during the induction of morphogenesis in vitro in leaf base and scale segment cultures at media supplemented either with 2,4-D and KIN or with TDZ was determined. Concentration of AGPs increased after seven days of cultivation of explants on media with growth regulators in the leaf base culture and 21 days in the scale segment culture. In the leaf base culture, concentration of AGPs in explants was higher on a medium with 2,4-D and KIN than on a medium with TDZ. The AGP profile obtained by crossed electroforesis reveiled the presence of one AGP type during induction of morphogenesis in vitro of F. meleagris. Univerzitet u Beogradu Biološki fakultet Subotić, Angelina Dragićević, Ivana 1961- Jevremović, Slađana 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=44 https://fedorabg.bg.ac.rs/fedora/get/o:2441/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41534735 sr Autorstvo 3.0 Srbija (CC BY 3.0)

oai:eteze.bg.ac.rs:45 2012-12-10T00:00:00Z 1

Моlеkulаrnа dеtеkciја i gеnоtipizаciја sојеvа pаrаzitа Toxoplasma gondii izоlоvаnih u Srbiјi Molecular detection and genotyping of Toxooplasma gondiistrains isolated in Serbia Vujanić, Marija, 1980- Toxoplasma gondii, tоksоplаzmоzа, diјаgnоstikа, mоlеkulаrnа dеtеkciја, PCR, PCR-RFLP, humаni mаtеriјаl, glоdаri, gеnоtipizаciја, sојеvi, pаrаzitа Toxoplasma gondii, toxoplasmosis, diagnostics, molecular detection, PCR, PCR-RFLP, human material, rodents, genotyping, parasite strains Datum odbrane: 09.07.2012. Тоksоplаzmоzа, оbоlјеnjе kоје izаzivа pаrаzit Toxoplasma gondii, јеdnа je оd nајrаsprоstrаnjеniјih zооnоzа u svеtu, i prоcеnjuје sе dа је čаk јеdnа trеćinа čоvеčаnstvа inficirаnа оvim pаrаzitоm. Iаkо sеrоlоški tеstоvi prеdstаvlјајu primаrnu mеtоdu u rutinskој diјаgnоstici tоksоplаzmоzе, intеrprеtаciја rеzultаtа sеrоlоških аnаlizа u nеkim kliničkim slučајеvimа mоžе biti kоmplikоvаnа i dugоtrајnа, а nеrеtkо i nеdоvоlјnо infоrmаtivnа. Zbоg tоgа је uvоđеnjе mоlеkulаrnih mеtоdа kоје inаčе оdlikuје vеlikа оsеtlјivоst i pоmоću kојih је mоgućе dоbiti rеzultаtе u krаtkоm vrеmеnskоm pеriоdu, оd vеlikоg znаčаја zа diјаgnоstiku tоksоplаzmоzе. Оtudа је cilј оvоg istrаživаnjа biо uvоđеnjе mоlеkulаrnе diјаgnоstikе tоksоplаzmоzе pо prvi put u Srbiјi, kао i gеnоtipizаciја izоlоvаnih sојеvа T. gondii. Оvоm studiјоm је оbuhvаćеnо 160 uzоrаkа pоrеklоm оd 127 pаciјеnаtа sеrоlоški suspеktnih nа tоksоplаzmоzu, kоd kојih је prisustvо T. gondii аnаlizirаnо PCR-оm u rеаlnоm vrеmеnu i biоlоškim оglеdоm. Pоkаzаnо је dа uspеšnоst dоkаzivаnjа DNK T. gondii u mаtеriјаlu humаnоg pоrеklа zаvisi kаkо оd tipа mаtеriјаlа tаkо i оd ukupnе zаprеminе mаtеriјаlа оd kојеg sе uzimа uzоrаk. Таkо је PCR u rеаlnоm vrеmеnu biо pоzitivаn u 30,8% uzоrаkа pеrifеrnе krvi, u 33,3% uzоrаkа krvi iz pupčаnikа, u 35,7% uzоrаkа plоdоvih vоdа, u 57,1% uzоrаkа likvоrа i u 60% uzоrаkа оčnih vоdicа. U оdnоsu nа izоlаciјu pаrаzitа biоlоškim оglеdоm, pоkаzаnа је znаtnо višа stоpа dеtеkciје DNK T. gondii, i tо i u uzоrcimа krvi оd pаciјеnаtа suspеktnih nа аkutnu tоksоplаzmоzu tаkо i u оnimа pоrеklоm оd fеtusа i nоvоrоđеnčаdi suspеktnih nа kоngеnitаlnu tоksоplаzmоzu. Dоbiјеni rеzultаti ukаzuјu prе svеgа nа vеliki pоtеnciјаl i prаktični znаčај mоlеkulаrnе diјаgnоstikе kао i nа pоtrеbu uvоđеnjа оvе mеtоdе kао dеlа stаndаrdnоg prоtоkоlа zа diјаgnоstiku tоksоplаzmоzе... Toxoplasmosis, infection caused by the parasite Toxoplasma gondii, is one of the most widespread zoonoses in the world and it has been estimated that up to one third of the global human population is infected with this parasite. Although serological tests are the primary method in the routine diagnosis of toxoplasmosis, interpretation of the results can be not only difficult and time-consuming, but they can be inconclusive. Therefore, the introduction of highly sensitive molecular methods, by which results can be obtained within a day, into the diagnosis of toxoplasmosis is of great importance. The aim of this research was the introduction of molecular methods into the diagnosis of toxoplasmosis for the first time in Serbia, as well as genotypization of the isolated T. gondii strains. This study included 160 human biological samples from 127 patients serologically suspected of toxoplasmosis in which the presence of T. gondii was analyzed by PCR and by bioassay in mice. It was found that the detection of T. gondii DNA in human biological materials depends on the type of sample as well as on the initial volume. Real-time PCR was positive in 30.8% of peripheral blood samples, 33.3% of cord blood samples, 35.7% of amniotic fluid samples, 57.1% of CSF samples and 60% of humor aqueous samples. The detection rate of T. gondii by molecular methods was higher than by bioassay, in both blood samples from adults suspected of acute toxoplasmosis and samples from fetuses and newborns suspected of congenital toxoplasmosis. The results of this study emphasize the huge practical importance and potential of molecular diagnostics and show the benefit of introducing this method as part of the standard protocol for the diagnosis of toxoplasmosis... Univerzitet u Beogradu Biološki fakultet Ivović, Vladimir Savić-Pavićević, Dušanka, 1972- Đurković-Đaković, Olgica 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=45 https://fedorabg.bg.ac.rs/fedora/get/o:2444/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41539087 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:46 2012-12-25T00:00:00Z 1

Ispitivanje uticaja aloe emodina na ćelije melanoma B16 i A375 i njihovu osetljivost na citostatike i imunski odgovor Evaluation of aloe emodin effect on B16 and A375 melanoma cells and their sensitivity to anticancer drugs and immune response Radović, Julijana M., 1975- Aloe emodin, melanom, ERK1/2, Akt, apoptoza, diferencijacija Aloe emodin, melanoma, ERK1/2, Akt, apoptosis, differentiation Datum odbrane : 28.9.2012. Aloe emodin (AE) spada u biljne molekule antraciklinskog tipa koji zahvaljujući reaktivnim grupama na atomima ugljenika benzenovih prstenova pokazuje izrazitu reaktivnost i posledično široki spektar biološke aktivnosti poput baktericidnog, fungicidnog, viricidnog, imunosupresivnog, antiinflamatornog, hepatoprotektivnog, laksativnog i vazorelaksirajućeg delovanja. Istraživanja novijeg datuma stavljaju u žižu interesovanja njegova antitumorska dejstva. Ciljevi koji su postavljeni u ovoj tezi podrazumevali su utvrđivanje tumoricidnog delovanja AE-a na ćelije mišjeg, B16 i humanog, A375 melanoma koje se inicijalno razlikuju u redoks statusu i aktivnosti signalnih puteva uključenih u kancerogenezu. Uz uporednu analizu unutarćelijskog odgovora pomenutih linija na tretman AE-om, ispitivan je i uticaja AE-a na osetljivost melanoma na imunski odgovor usmeren protiv transformisane ćelije kao i na efikasnost konvencionalne citostatske terapije. AE je snažno inhibirao rast obe ćelijske linije posredstvom različitih mehanizama. U slučaju A375 ćelija, AE je doveo do indukcije apoptoze zavisne od aktivnosti kaspaza uz smanjenje nivoa antiapoptotskih proteina XIAP i Bcl-2. Suprotno, tretman AE-om je indukovao ireverzibilnu diferencijaciju B16 ćelija u smeru primarnog fenotipa manifestovanog povećanom ekspresijom enzima tirozinaze i naknadnom produkcijom melanina. Opisana promena B16 ćelija bila je praćena brzom akumulacijom p53, ciklina D1 i D3. Ključni događaj u diferencijaciji B16 ćelija je, najverovatnije, povećana produkcija H2O2 indukovana AE-om. U osnovi heterogenih ishoda tretmana istovetnim agensom je recipročna regulacija aktivnosti ERK1/2 i Akt. Poseban značaj ima podatak da se apoptoza pokrenuta AE-om u A375 ćelijama odvija u uslovima prekomerne aktivnosti Akt. Analiza paralelnog tretmana ćelija melanoma AE-om i konvencionalnim citostaticima (doksorubicin i paklitaksel) pokazala je da pomenuta supstanca umanjuje efikasnost hemioterapije. Nekonzistentnost ishoda ko-tretmana AE-a i medijatora imunskog odgovora iz familije TNF molekula ukazala je na kompleksnost uticaja mikrosredine na učinak AE-a. U celini, rezultati ove doktorske disertacije pokazuju kako specifičnost ćelija melanoma definiše mehanizam delovanja AE-a iako ne ugrožava njegov antitumorski potencijal. S druge strane, opisani rezultati upozoravaju na opasnost kombinovanja biljnih preparata sa konvencionalnim terapeuticima usled mogućeg neutrališućeg efekta. Aloe emodin is an herbal antraquinone that, due to reactive groups on the carbon atoms of benzene rings, posseses a strong reactivity and consequently shows a wide range of biological activities such as antibacterial, antifungal, antiviral, diuretic, immunosuppressive, anti-inflammatory, hepatoprotective, laxative and vasorelaxant. Recent studies put the focus on its antitumor effects. The aim of this thesis was to determine and evaluate antitumor activity of AE on two melanoma cell lines that initially differs in redox status and activities of signaling pathways involved in carcinogenesis: mouse melanoma B16, and human melanoma A375 cells. Together with comparative analysis of the intracellular responses of two lines to the AE treatment, the impact of AE on the sensitivity of melanoma to antitumor immune response as well as the efficiency of conventional cytostatic therapy, were examined. AE decreased the growth of both cell lines through different mechanisms. In the case of A375 cells, AE inducted caspase dependent apoptosis by reducing protein levels of antiapoptotic molecules XIAP and Bcl-2. In contrast, treatment with AE promoted irreversible differentiation of B16 cells towords its primary phenotype manifested through increased expression of the tyrosinase and the subsequent production of melanin. Described change in B16 cells was accompanied by a rapid accumulation of p53, cyclin D1 and D3. Increased production of H2O2 triggered by AE is probably first in a line of events responsible for induction of differentiation of B16 cells. Opposite regulation of two main signaling pathways involved in cell proliferation, differentiation and death- MEK-ERK1/2 and PI3K-Akt in tested cell lines could be essential for different outcome of the treatment with single agent. Furthermore, analysis of the parallel treatment of melanoma cells with the AE and conventional cytostatics (doxorubicin and paclitaxel) showed that introduced substance decreases the effectiveness of chemotherapy. Incoherent outcome of co-treatment of AE and TNF, FasL or TRAIL, the most relevant mediators of nonspecific immune response aginst tumor cells, points to the complexity of the influence of microenvironmental factors to the effect of AE. In general, the results of this PhD thesis show that cell specificity of melanomas defines the mechanism of AE action, while it does not jeopardize its anticancer potential. On the other hand, presented results point to a danger of combining herbal medicines with conventional therapeutics due to their possible neutralizing effects. Univerzitet u Beogradu Biološki fakultet Maksimović-Ivanić, Danijela Kataranovski, Milena, 1952- Mijatović, Sanja Stošić-Grujičić, Stanislava Božić, Biljana 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=46 https://fedorabg.bg.ac.rs/fedora/get/o:2765/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024530098 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:47 2012-12-27T00:00:00Z 1

Efekti B hromozoma na genetičku varijabilnost i strukturu populacija žutogrlog miša Apodemus flavicollis (Mammalia, Rodentia) Effects of B chromosomes on genetic variability and population structure in yellow-necked mouse Apodemus flavicollis (Mammalia, Rodentia) Adnađević, Tanja B., 1978- Apodemus flavicollis, B hromozomi, populaciona genomika, AFLP, selekcija, adaptacija Apodemus flavicollis, B chromosomes, population genomics, AFLP, selection, adaptation Datum odbrane: 11.09.2012. B hromozomi predstavljaju prekobrojne hromozome koji nisu neophodni za normalan rast i razviće svojih nosilaca. Dosadašnja istraživanja, na različitim vrstama, su pokazala da B hromozomi nisu inertni i da se njihovi efekti u različitom stepenu manifestuju od molekularnog do populacionog nivoa. Jedna od vrsta roda Apodemus, kod koje su prisutni B hromozomi, jeste žutogrli miš Apodemus flavicollis, koja je rasprostranjena u Palearktiku. U cilju utvrđivanja efekata B hromozoma analizirane su četiri populacije vrste A.flavicollis sa različitom frekvencom B hromozoma, iz topološki i ekološki različitih staništa iz Srbije. Genotipizacija je izvršena multilokusnom metodom AFLP (Amplified Fragment Lenght Polymorphism) i primenom 14 prajmerskih kombinacija je dobijen ukupno 471 marker. Detektovane su značajne razlike u genetičkom diverzitetu i diferenciranosti među analiziranim populacijama A. flavicollis. Najveći genetički diverzitet je detektovan u populaciji sa lokaliteta Fruška gora koji predstavlja optimalno stanište za datu vrstu. Ispitivanje na nivou individua je pokazalo postojanje većih genetičkih razlika između jedinki sa B hromozomima, nego između jedinki bez B hromozoma, kako unutar populacija tako i između populacija. Razlika između jedinki sa i bez B hromozoma nije detektovana ispitivanjem na nivou populacija, ali je detektovana razlika u alelskim frekvencama između ove dve grupe jedinki. Raščlanjivanje genetičke varijabilnosti na različitim populacionim nivoima je pokazalo da je najveći deo genetičke varijabilnosti raspoređen na interpopulacionom i individualnom nivou. Genetičke razlike između jedinki sa i bez B hromozoma nisu detektovane. Visok nivo diferencijacije populacije na osnovu lokaliteta je potvrđen prostornom analizom molekularne varijanse, dok je nepostojanje korelisanosti genetičkih i geografskih distanci pokazalo da nisu genetički diferencirane uprkos udaljenosti. U ovom slučaju veliku genetičku Rezime/Summary diferenciranost između ispitivanih populacija možemo da objasnimo postojanjem lokalnih adaptacija. Ukupno dvanaest lokusa je detektovano kao mogući lokusi pod delovanjem selekcije ili koji se nalaze blizu lokusa koji su pod delovanjem selekcije. Tri lokusa su detektovana u svim populacijama, dok je ostalih devet karakteristično ili za populaciju sa nižom (Fruška gora) ili za populacije sa višom frekvencom B hromozoma (Tara, Devojački bunar i Lisine). S obzirom na to da su jedinke iz topološki i ekološki različitih staništa, pretpostavili smo da postoje različiti selekcioni pritisci u zavisnosti od toga da li je stanište optimalno za vrstu ili ne. Testiranje uticaja različitih sredinskih varijabli, koje su značajne za ovu vrstu, pokazalo je da je najveći broj asocijacija AFLP lokusa i sredinskih varijabli detektovan za dve varijable koje su bitne za populacionu dinamiku odnosno za dostupnost hrane koju preferiraju i reprodukciju vrste A. flavicollis. Selekcioni pritisci koje nameću dužina zime i leta bi mogli da predstavljaju glavni mehanizam variranja frekvence B hromozoma kako unutar populacija, tako i između populacija iz različitih staništa. U ispitivanim populacijama nije potvrđen efekat B hromozoma na genetički diverzitet i diferenciranost populacija. Pretpostavljamo da selekcija izazvana ekološkim faktorima dovodi do adaptiranosti populacija na specifične uslove sredine i direktno delujući na mehanizam transmisije B hromozoma favorizuje jedinke sa B hromozomima u populacijama koje naseljavaju staništa koja nisu optimalna za datu vrstu. Moguće je da su epistatički ili slabi aditivni efekti B hromozoma efikasniji u neoptimalnim sredinama, mada se ne sme zanemariti i moguće postojanje epigenetičkih procesa koji dovode do modifikacije u ekspresiji gena. U ovom slučaju B hromozomi imaju adaptivnu ulogu čime se potvrđuje heterotični model održavanja B hromozoma u populacijama iz Srbije. B chromosomes (Bs) are supernumerary to the standard set of chromosomes characterized with dispensable nature. Studies on various species, showed that they are not inert, with expression of their effects on different levels from molecular to population level. One of the species from genus Apodemus with B chromosomes, yellow-necked mouse Apodemus flavicollis, is widespread in Palearctic. In order to determine effects of Bs, four populations of A. flavicollis from localities in Serbia, differing in both topological and ecological conditions, as well as frequency of Bs, were examined. Genotyping was done by AFLP (Amplified Fragment Lenght Polymorphism) multiloci method, and 14 primer combinations produced 471 marker. We detected significantly different level of genetic diversity and differentiation between studied populations. Greatest genetic diversity was detected for Fruška gora population, settled in locality with optimal condition for this species. Band based approach estimated greatest genetic differencies between individuals with Bs, in comparison with individuals without Bs, on interpopulation as well as intrapopulation level. Allele frequency based approach did not detect difference between individuals with and without Bs, but it showed difference in alelle frequencies between these two groupes. Partitioning of genetic variability showed that majority of genetic variability is distributed on interpopulation and individual level. Genetic differencies between individuals with and without Bs were not detected. Spatial analysis of molecular variance confirmed high level of genetic differentation based on locality, while lack of correlation of genetic and geographic distances showed that population are not differentiated due to spatial separation. In this case, high level of genetic differentation detected between populations could be explained by local adaptation. Total of twelve loci were Rezime/Summary detected as loci under selection or close to loci under selection. Three of these loci were detected in all populations, while remaining nine were unique to either population with lower frequency (Fruška gora) or populations with higher frequency of Bs (Tara, Devojački bunar and Lisine). Considering the fact that population are settled on topologicaly and ecologicaly different habitats, we assumed existance of different selection preassures based on the optimality of habitat for this species. Analysis of assosiation of environmental variables ecologicaly important for this species with AFLP markers showed that the greatest number of associations was detected for two variables that could influence population dynamics of A. flavicollis, by affecting availability of preferred food and timing of reproduction. Selection pressures imposed by duration of winter and summer could represent main factors of Bs frequency variation at intrapopulation and interpopulation level. Effect of Bs on genetic diversity and differentiation was not detected in analyzed populations. Ecologically based selection led to adaptation of populations to different habitats, directly acting on mechanism of Bs transmission, favoring individuals with Bs in populations settled in habitats suboptimal for this species. It is possible that epistatic or very small additive effects of Bs are more effective in suboptimal environments, but their epigenetic effects, like modification of the expression of certain genes, could not be excluded either. In this case Bs can be considered as adaptive, confirming heterotic model of B chromosomes maintenance in populations from Serbia. Univerzitet u Beogradu Biološki fakultet Blagojević, Jelena Cvetković, Dragana, 1961- Vujošević, Mladen 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=47 https://fedorabg.bg.ac.rs/fedora/get/o:2774/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024498610 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:48 2013-01-11T00:00:00Z 1

Ispitivanje senzitivnosti genoma kod pacijenata sa bolestima hromozomske nestabilnosti . Genome sensitivity in patients with chromosomal instability disorders Ćirković, Sanja S. 1977- Fankonijeva anemija (FA), Nijmegenov sindrom nestabilnosti (NSN), diepoksibutan (DEB), bleomicin (BLC), hromozomska nestabilnost, citogenetika, komet test, analiza ćelijskog ciklusa, c.657_661del5 mutacija Fanconi’s anemia (FA), Nijmegen Breakage syndrome (NBS), diepoxybutane (DEB), bleomycin (BLC), chromosomal fragility, cytogenetic, comet assay, cell cycle, c.657_661del5 mutation Datum odbrane: 29.10.2012 U cilju ispitivanja senzitivnosti genoma i potvrde klinički postavljene dijagnoze bolesti hromozomske nestabilnosti, korišćeni su uzorci dve grupe pacijenata sa kliničkom slikom: Fankonijeve anemije (FA) i Nijmegenovog sindroma nestabilnosti (NSN) (eng. Nijmegen Breakage syndrome, NBS). Specifična hipersenzitivnost ćelija obolelih od FA na diepoksibutan (DEB), odnosno kod obolelih od NSN na bleomicin (BLC), iskorišćena je u diferencijalno dijagnostičke svrhe. Studija je obuhvatila ukupno 100 pacijenata: 90/100 sa kliničkom slikom FA i 10/100 pacijenata sa kliničkim znacima NSN, koji su dijagnostikovani na Institutu za zdravstvenu zaštitu majke i deteta Srbije „Dr Vukan Čupić“. U detekciji DEB-om indukovane hromozomske nestabilnosti obolelih od FA primenjene su standardne citogenetičke metode. Za potvrdu ili isključenje mozaičnog fenotipa FA korišćene su dodatne metode: analiza oštećenja DNK komet testom i protočno citometrijska analiza zastoja ćelija u G2 fazi ćelijskog ciklusa. Hromozomska osetljivost ćelija obolelih od NSN je analizirana primenom bleomicinovog testa (BLC test). Molekularna analiza prisustva ili odsustva c.657_661del5 mutacije u NBN genu obolelih od NSN, urađena je korišćenjem modifikovane PCR metode uz analizu heterodupleksa. Kod 11,11% (10/90) pacijenata pod sumnjom da boluju od FA (FA grupa), otkrivena je povećana hromozomska osetljivost na DEB u odnosu na kontrolnu grupu (Mann-Whitneyev test: p < 0,05), dok su kod 3,33% (3/90) pacijenata dobijene granične vrednosti iste analize (FA* grupa). U cilju preciznijeg klasifikovanja pacijenata u FA grupi, primenjen je indeks hromozomske fragilnosti. Na ovaj način je u FA grupi, kod 40% (4/10) pacijenata otkriven ćelijski fenotip FA nemozaičnog tipa, dok je kod 60% (6/10) pacijenata dobijen mozaični odgovor na DEB. Kod svih pacijenata sa mozaičnim fenotipom FA, kao i kod dva pacijenta sa graničnim vrednostima diepoksibutanovog testa (DEB testa), daljim analizama primenom komet testa i analizom zastoja ćelija u G2 fazi, potvrđena je dijagnoza FA. U drugoj grupi od 10 bolesnika sa sumnjom da boluju od NSN analizirana je BLC-om indukovana hromozomska nestabilnost, koja je bila povećana kod 40% (4/10) pacijenata (NBS grupa). Kod 30% (3/10) pacijenata dobijeni rezultati su se preklapali sa rezultatima kontrolne grupe (ne-NBS grupa), dok je kod preostala tri pacijenta analiza bila neuspešna zbog slabog mitotskog indeksa. Molekularnim analizama je otkriveno homozigotno prisustvo c.657_661del5 mutacije u NBN genu kod sva četiri pacijenta iz NBS grupe, kao i kod tri pacijenta kod kojih je citogenetička analiza bila neuspešna, i tako potvrđena konačna dijagnoza NSN. Na osnovu dobijenih rezultata može se zaključiti da su analize korišćene u ovoj studiji omogućile potvrdu klinički postavljene dijagnoze FA i NSN, što opravdava njihovu dalju primenu u diferencijalnoj dijagnostici ovih oboljenja. In order to determine the sensitivity of the genome and to confirm a clinical diagnosis of chromosomal instability disorders, blood samples from patients with clinical suspicion of Fanconi’s anemia (FA) and Nijmegen Breakage syndrome (NBS), were collected for chromosome fragility evaluation by the diepoxybutane (DEB) and bleomycin (BLC) tests. The study considered a total of 100 patients: 90/100 with the hematological and/or congenital phenotypic symptoms reminiscent of FA and 10/100 patients with clinical features of NBS, all diagnosed at the Mother and Child Health Care Institute of Serbia "Dr Vukan Čupić”. The DEB-induced chromosomal fragility analysis in patients with FA symptoms was carried out by using standard cytogenetic methods. The additional methods, such as: DNA damage analysis by comet assay and flow cytometric analysis of G2 phase cell cycle arrest, were used in order to confirm FA phenotype in patients with mosaic cytogenetic response to DEB. Chromosomal sensitivity of cells in patients with NBS symptoms was analyzed using a BLC test. Molecular analysis for the presence of the c.657_661del5 mutation in NBN gene in patients with NBS was carried out using modified PCR method and heteroduplex analysis on PAGE gel. In this study 11.11% (10/90) of patients with clinical suspicion of FA were found to have an increased chromosomal sensitivity to DEB (FA group), comparing to healthy controls (Mann-Whitney test: p < 0.05), while 3.33% (3/90) of patients showed borderline results of the same analysis (FA* group). The chromosome fragility index was used in order to provide a clear cut-off diagnostic level distinguishing FA mosaic from other patients in the FA group. In this group, 40% (4/10) of FA patients revealed non-mosaic FA phenotype, while the remaining 60% (6/10) of FA patients showed a mosaic response to DEB. In all of FA mosaic patients, and two patients with borderline DEB-sensitivity, further analyses were performed using comet assay and analysis of G2 phase cell cycle arrest, in order to confirm the diagnosis of FA. In the second group of 10 patients with clinical suspicion of NBS, the cytogenetic analysis revealed an increased chromosomal sensitivity to BLC in 40% (4/10) of them (NBS group). The BLC-induced chromosome fragility values in 30% (3/10) of these patients were overlapping those in the control group (non-NBS group). In the remaining of three patients the cytogenetic analysis was unsuccessful, due to the low mitotic index. Molecular analysis confirmed the presence of homozygous c.657_661del5 mutation in all seven NBS patients, including three patients with unsuccessful cytogenetic analysis, which confirmed the final diagnosis of NBS. Based on these results it can be concluded that the analyses used in this study are useful in confirmation of clinical diagnosis of FA and NBS, which justifies their further application in the differential diagnosis of these two diseases. Univerzitet u Beogradu Biološki fakultet Guć-Šćekić, Marija Milašin, Jelena 1957- Vuković-Gačić, Branka 1958- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=48 https://fedorabg.bg.ac.rs/fedora/get/o:3033/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024511666 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:49 2013-01-11T00:00:00Z 1

Bioinformatička i glikobiohemijska analiza modularne organizacije CA125 antigena čoveka Bioinformatic and glycobiochemical analysis of human CA125 antigen modular organization Mitić, Ninoslav M., 1982- CA125 antigen, in silico analiza, glikobiohemijska analiza, eritrociti, adhezija, leukocitni receptori, sigleci, selektini, DC-SIGN, manozni receptor makrofaga CA125 antigen, in silico analysis, glycobiochemical analysis, erythrocytes, adhesion, leukocyte receptors, siglecs, selectins, DC-SIGN, macrophage mannose receptor Datum odbrane: 9.11.2012. CА125 antigen, poznat kao marker seroznog karcinoma ovarijuma, predstavlja ekstracelularni deo mucina 16 (MUC16), koji nastaje njegovom proteolitiĉkom degradacijom. МUC16 pripada grupi transmembranskih proteina tipa I, i eksprimiran je u velikom broju embrionalnih, ali i adultnih tkiva. Njegovu primarnu strukturu karakteriše prisustvo tri regiona: N-terminalni region i region tandemskih ponovaka, koji su smešteni ekstracelularno, i C-terminalni region, koji se sastoji od transmembranskog dela i kratkog citoplazmatskog repa. Ekstracelularni region je intenzivno glikozilovan, a u intracelularnom regionu se nalazi potencijalno mesto fosforilacije. Fosforilacija predstavlja signal za proteolizu i oslobaĊanje ekstracelularnog dela molekula (СА125 antigen), koji se kao takav može detektovati u razliĉitim telesnim teĉnostima. Biološka uloga MUC16/CA125, još uvek nije razjašnjena. Dosadašnja ispitivanja funkcije MUC16 (membranska forma) su, uglavnom, bila bazirana na in vitro model sistemu ćelija ovarijalnog karcinoma, dok su literaturni podaci o aktivnosti CA125 antigena (solubilna forma) veoma retki. Solubilna forma predstavlja funkcionalni analog i kompetitor membranskoj formi i, u cirkulaciji, ona prva dospeva u kontakt sa razliĉitim tipovima normalnih ili patološki izmenjenih ćelija, ali ne postoje eksperimentalni dokazi o mogućem uticaju na njihovu adhezivnost, kao i imunomodulatorna svojstva. U ovom radu je ispitivana modularna organizacija MUC16/CA125 na bioinformatiĉkom i glikobiohemijskom nivou, sa ciljem da se bliže definišu biološki kapacitet i posebnosti prezentacije ovog molekula u kontekstu interaktoma ĉoveka. Bioinformatiĉka analiza, kao deo strategije za otkrivanje moguće biološke uloge MUC16/CA125, do sada nije korišćena u ispitivanjima ovog antigena. Pored toga, u kontekstu diskretnih bioloških funkcija, bez obzira na izuzetan biomedicinski znaĉaj, ne postoje eksperimentalni podaci o interakcijama MUC16/CA125 sa specifiĉnim klasama receptora na ćelijama krvnog sistema.CА125 antigen, poznat kao marker seroznog karcinoma ovarijuma, predstavlja ekstracelularni deo mucina 16 (MUC16), koji nastaje njegovom proteolitiĉkom degradacijom. МUC16 pripada grupi transmembranskih proteina tipa I, i eksprimiran je u velikom broju embrionalnih, ali i adultnih tkiva. Njegovu primarnu strukturu karakteriše prisustvo tri regiona: N-terminalni region i region tandemskih ponovaka, koji su smešteni ekstracelularno, i C-terminalni region, koji se sastoji od transmembranskog dela i kratkog citoplazmatskog repa. Ekstracelularni region je intenzivno glikozilovan, a u intracelularnom regionu se nalazi potencijalno mesto fosforilacije. Fosforilacija predstavlja signal za proteolizu i oslobaĊanje ekstracelularnog dela molekula (СА125 antigen), koji se kao takav može detektovati u razliĉitim telesnim teĉnostima. Biološka uloga MUC16/CA125, još uvek nije razjašnjena. Dosadašnja ispitivanja funkcije MUC16 (membranska forma) su, uglavnom, bila bazirana na in vitro model sistemu ćelija ovarijalnog karcinoma, dok su literaturni podaci o aktivnosti CA125 antigena (solubilna forma) veoma retki. Solubilna forma predstavlja funkcionalni analog i kompetitor membranskoj formi i, u cirkulaciji, ona prva dospeva u kontakt sa razliĉitim tipovima normalnih ili patološki izmenjenih ćelija, ali ne postoje eksperimentalni dokazi o mogućem uticaju na njihovu adhezivnost, kao i imunomodulatorna svojstva. U ovom radu je ispitivana modularna organizacija MUC16/CA125 na bioinformatiĉkom i glikobiohemijskom nivou, sa ciljem da se bliže definišu biološki kapacitet i posebnosti prezentacije ovog molekula u kontekstu interaktoma ĉoveka. Bioinformatiĉka analiza, kao deo strategije za otkrivanje moguće biološke uloge MUC16/CA125, do sada nije korišćena u ispitivanjima ovog antigena. Pored toga, u kontekstu diskretnih bioloških funkcija, bez obzira na izuzetan biomedicinski znaĉaj, ne postoje eksperimentalni podaci o interakcijama MUC16/CA125 sa specifiĉnim klasama receptora na ćelijama krvnog sistema.In silico analiza modularne organizacije MUC16/CA125, vršena je na osnovu podataka koji su preuzeti sa UniProtKB baze podataka, a koji se odnose na molekul izolovan iz ćelijske linije ovarijalnog karcinoma ĉoveka, OVCAR-3. Bioinformatiĉka analiza je obuhvatila: odreĊivanje homologije (korišćenjem BLAST, Basic Local Alignment Search Tool alatke); ispitivanje prisustva obrazaca, strukturnih motiva i konzerviranih domena (korišćenjem baza podataka kao što su Bgee: a dataBase for Gene Expression Evolution i Gene Ontology, CDD, ELM, BLOCKS, InterProScan, MyHits i iProClass); odreĊivanje fiziĉko-hemijskih osobina, globularnosti i odstupanja od pretpostavljene tercijarne strukture (korišćenjem ProtParam, ProtScale i GLOBPLOT v2.3 alatki); i predviĊanje funkcije pomoću alatki koje koriste nekoliko programa: JAFA, ProtFun 2.2 i GeneOntology. Glikobiohemijska analiza je obuhvatila ispitivanje uticaja CA125 antigena na adhezivnost i agregabilnost eritrocita, kao i moguće interakcije sa razliĉitim tipovima leukocitnih lektina tj. sigleka (Siglec - sialic acid-binding immunogobulin (Ig)-like lectin) i receptora sliĉnih lektinima tipa C (selektini, DC-SIGN - dendritic cell-specific ICAM-3-grabbing non-integrin 1, MMR - macrophage mannose receptor). Ispitivanje efekta CA125 antigena na eritrocite ĉoveka odreĊivano je u testovima na ĉvrstoj fazi ili primenom svetlosne mikroskopije. Interakcija CA125 antigena sa leukocitnim receptorima ispitivana je pomoću lektinskog- i imunoblota, kao i u testovima vezivanja i inhibicije na ĉvrstoj fazi, sa imobilisanim antigenima. Glikobiohemijskom analizom su, pored antigena iz ćelijske linije ovarijalnog karcinoma ĉoveka (clCA125), bili obuhvaćeni i antigen kancerskog porekla iz pleuralne teĉnosti (pfCA125) kao i antigen fetalnog porekla (pCA125), koji se sintetiše tokom trudnoće. Rezultati in silico analize proteinske sekvence MUC16/CA125, stavili su ovaj molekul u kontekst modularnih proteina sa anotiranom ulogom u adheziji i srodnim procesima. Uvid u sekvence koje pokazuju sliĉnost sa sekvencom MUC16/CA125, pokazao je da se one, uglavnom, nalaze u ekstracelularnom regionu MUC16, koji je bogat serinom i treoninom. Ove sliĉnosti se nisu mogle povezati sa anotiranim domenima iz dostupnih baza podataka, osim parcijalno, ali statistiĉki znaĉajno sa BLLF1, multidomenom karakteristiĉnim za glikoproteine omotaĉa virusa iz familije Herpesviridae. Bioinformatiĉka analiza je ukazala i na moguću korelaciju funkcionalnih aktivnosti, koje se pripisuju domenima bogatim serinom/treoninom kod identifikovanih proteina u okviru ispitivanih taksona, i moguće funkcije CA125 antigena. Na osnovu dobijenih rezultata, uloga CA125 antigena u procesima adhezije bi mogla ukljuĉiti i interakcije posredstvom konzerviranih proteinskih sekvenci, odgovornih za jonski transport, i interakcije sa šećernim supstratima. Polazeći od mucinske prirode CA125 antigena, kao i fizioloških stanja u kojima je njegova koncentracija u serumu povećana, u prvom delu glikobiohemijske analize, ispitan je uticaj CA125 antigena na eritrocite ĉoveka. Dobijeni rezultati su ukazali da pCA125 i pfCA125 umereno povećavaju agregaciju eritrocita, i uspešno inhibiraju njihovu adheziju. Za razliku od njih, clCA125 je pokazao neznatan uticaj na modulaciju ovih osobina eritrocita. Sumarni rezultati drugog dela analize, koja se odnosila na interakcije sa leukocitnim receptorima, pokazali su da CA125, kao ligand, može stupiti u interakcije sa razliĉitim tipovima proteina koji vezuju sijalinsku kiselinu. Pokazano je da postoje specifiĉni obrasci vezivanja sigleka za ispitivane CA125 antigene, kojima se ovi antigeni, uspešnije, razlikuju u odnosu na njihovo poreklo, nego što se to ĉini na osnovu obrazaca vezivanja biljnih lektina, takoĊe specifiĉnih za sijalinsku kiselinu. Najuoĉljivija razlika je zapažena u odnosu na ligandni kapacitet CA125 antigena fetalnog porekla prema sigleku-7, prisutnom na dendritskim ćelijama, NK (natural killer cell) ćelijama, monocitima i CD8+ T ćelijama i clCA125 antigena kancerskog porekla prema sigleku-9 i sigleku-10, prisutnim na B ćelijama, NK ćelijama, monocitima, neutrofilima i CD8+ T ćelijama. Za razliku od sigleka, sva tri ispitivana selektina: L-selektin, E-selektin i P-selektin su, na dozno-zavisan naĉin, interagovali sa pfCA125 i u manjoj meri pCA125, ali ne i clCA125. Pored toga, zapaženo je i da je P-selektin reagovao na znatno nižim koncentracijama nego L- i E-selektin. Na osnovu uoĉenog visokog afiniteta P-selektina, CA125 antigen bi pre stupio u interakcije sa aktiviranim endotelnim ćelijama ili krvnim ploĉicama, na kojima je ovaj selektin prisutan, nego sa ćelijama na kojima su prisutni drugi tipovi selektina. Ispitivanje interakcije CA125 antigena i DC-SIGN, koji je eksprimiran na površini dendritskih ćelija (DC) i koji vezuje manan i visoko-manozne glikane kao i glikane sa terminalnim Lex/Ley/Lea/Leb antigenima, pokazalo je da on prepoznaje pCA125 i pfCA125 antigen. Rezultati inhibicije su ukazali da je vezivanje DC-SIGN za pCA125 zavisno od prisustva glikana bogatih manozom, za razliku od vezivanja pfCA125, koje je nezavisno od prisustva N- ili O-glikana, što bi moglo uticati na njegove diskretne receptorske funkcije. Manozni receptor makrofaga (MMR), koji je prisutan na makrofagama i DC i koji vezuje terminalnu manozu i fukozu i SLex, nije reagovao ni sa jednim od ispitivanih CA125 antigena. Receptori sliĉni lektinima tipa C imaju važnu ulogu u imunskom sistemu, u smislu posredovanja u interakcijama tipa ćelija-ćelija, tj. u meĊusobnom kontaktu leukocita ili u njihovom kontaktu sa endotelom, kao i u vezivanju patogena. Promene u glikozilaciji liganada za receptore sliĉne lektinima tipa C, direktno utiĉu na njihovu aktivnost i specifiĉnost i imaju važne posledice na razvoj, preživljavanje i reaktivnost ćelija krvnog i imunskog sistema. Rezultati ovoga rada ukazuju da bi razlike u strukturi/glikozilaciji CA125 antigena, koje se vezuju za posebna fiziološka i patološka stanja, mogle menjati njegov uticaj na ćelije krvnog sistema ĉoveka i imati znaĉajne biomedicinske posledice u razliĉitim mikrosredinama. Dalji uvid u prirodu i mehanizme multifunkcionalnosti CA125 antigena zahteva interdisciplinarni pristup baziran na kompleksnim interakcijama koje su posredovane razliĉitim strukturnim domenima. CA125 antigen, a well known tumour marker for serous ovarian cancer, is an extracellular part of the mucin 16 (MUC16) molecule. This antigen arises from proteolytic degradation of MUC16, a type I transmembrane protein, expressed in both embrional and adult tissue. The primary structure of MUC16 consists of three characteristic parts: an N-terminal region and a series of tandem repeats, which are located extracellularly, and a C-terminal region, which consists of the transmembrane part and a short cytoplasmic tail. The extracellular peptide is extensively glycosylated, and there is a potential phosphorylation site in the intracellular chain. Phosphorylation is a signal for proteolysis and release of the extracellular part of the molecule (CA125 antigen), which can be detected as such in various body fluids. The biological role of MUC16/CA125 is not yet understood. Previous investigations of MUC16 (membrane form) functions were generally based on in vitro cell model systems of ovarian cancer, whereas published data on the activity of CA125 antigen (soluble form) are very rare. The soluble form is a functional analog and competitor to the membrane form, and, in the circulation, it first contacts different types of normal or pathologically altered cells. However, there is no experimental evidence on its possible impact on their adhesion nor immunomodulatory properties. In this work, the modular organization of human CA125 antigen was analyzed bioinformatically and glycobiochemically, aiming at closer definition of the biological capacity and presentation of this molecule in the context of the human interactome. As part of a strategy to detect a possible biological role for MUC16/CA125, bioinformatics analysis has never been used in studies of this antigen. In addition, in the context of discrete biological functions, regardless of its great biomedical importance, there are no CA125 antigen, a well known tumour marker for serous ovarian cancer, is an extracellular part of the mucin 16 (MUC16) molecule. This antigen arises from proteolytic degradation of MUC16, a type I transmembrane protein, expressed in both embrional and adult tissue. The primary structure of MUC16 consists of three characteristic parts: an N-terminal region and a series of tandem repeats, which are located extracellularly, and a C-terminal region, which consists of the transmembrane part and a short cytoplasmic tail. The extracellular peptide is extensively glycosylated, and there is a potential phosphorylation site in the intracellular chain. Phosphorylation is a signal for proteolysis and release of the extracellular part of the molecule (CA125 antigen), which can be detected as such in various body fluids. The biological role of MUC16/CA125 is not yet understood. Previous investigations of MUC16 (membrane form) functions were generally based on in vitro cell model systems of ovarian cancer, whereas published data on the activity of CA125 antigen (soluble form) are very rare. The soluble form is a functional analog and competitor to the membrane form, and, in the circulation, it first contacts different types of normal or pathologically altered cells. However, there is no experimental evidence on its possible impact on their adhesion nor immunomodulatory properties. In this work, the modular organization of human CA125 antigen was analyzed bioinformatically and glycobiochemically, aiming at closer definition of the biological capacity and presentation of this molecule in the context of the human interactome. As part of a strategy to detect a possible biological role for MUC16/CA125, bioinformatics analysis has never been used in studies of this antigen. In addition, in the context of discrete biological functions, regardless of its great biomedical importance, there are no experimental data on the interactions of MUC16/CA125 with specific classes of receptors on cells of the blood system. The modular organization of MUC16/CA125, was analyzed in silico using data taken from the UniProtKB database, which refers to a molecule isolated from the human ovarian cancer cell line, OVCAR-3. Bioinformatic analysis included: determination of homology (using BLAST, Basic Local Alignment Search Tool Tool); investigation of patterns, structural motifs and conserved domains (using databases such as Bgee: a database for Gene Expression and Gene Ontology Evolution, CDD, ELM, BLOCKS, InterProScan and MyHits iProClass); determination of physical and chemical properties, globularity and deviations from the assumed tertiary structure (using ProtParam, ProtScale and GLOBPLOT v2.3 tools); and function prediction using tools that employ several programs: JAFA, ProtFun 2.2 and GeneOntology. Glycobiochemical analysis comprised examination of the influence of CA125 on adhesion and aggregation of erythrocytes, as well as on interactions with different types of leukocyte lectins, namely siglecs [sialic acid-binding immunogobulin (Ig)-like lectin] and C-type lectin-like receptors [selectins, dendritic cell-specific ICAM-3-grabbing non-integrin 1 (DC-SIGN) and macrophage mannose receptor (MMR)]. The effect of CA125 antigen on human erythrocytes was determined using solid phase tests and light microscopy. The interaction of CA125 with leukocyte receptors was investigated employing lectin-blot and immunoblot, as well as binding and inhibition solid phase assays. Cancer antigen isolated from human pleural fluid (pfCA125) and pregnancy-associated antigen (pCA125) were included in the glycobiochemical analysis in addition to antigen from the human ovarian carcinoma cell line (clCA125). The results of in silico analysis placed MUC16/CA125 in the context of modular proteins with an annotated role in adhesion-related processes. They pointed to similarities within extracellular serine/threonine rich regions of MUC16 to protein sequences expressed in evolutionarily distant taxa. No relation to annotated domains from available databases appeared, except for BLLF1, a multidomain characteristic of virus envelope glycoproteins of the Herpesviridae family. Bioinformatics analysis also pointed to a possible correlation between functional activities, which are attributed to serine/threonine rich domains of experimental data on the interactions of MUC16/CA125 with specific classes of receptors on cells of the blood system. The modular organization of MUC16/CA125, was analyzed in silico using data taken from the UniProtKB database, which refers to a molecule isolated from the human ovarian cancer cell line, OVCAR-3. Bioinformatic analysis included: determination of homology (using BLAST, Basic Local Alignment Search Tool Tool); investigation of patterns, structural motifs and conserved domains (using databases such as Bgee: a database for Gene Expression and Gene Ontology Evolution, CDD, ELM, BLOCKS, InterProScan and MyHits iProClass); determination of physical and chemical properties, globularity and deviations from the assumed tertiary structure (using ProtParam, ProtScale and GLOBPLOT v2.3 tools); and function prediction using tools that employ several programs: JAFA, ProtFun 2.2 and GeneOntology. Glycobiochemical analysis comprised examination of the influence of CA125 on adhesion and aggregation of erythrocytes, as well as on interactions with different types of leukocyte lectins, namely siglecs [sialic acid-binding immunogobulin (Ig)-like lectin] and C-type lectin-like receptors [selectins, dendritic cell-specific ICAM-3-grabbing non-integrin 1 (DC-SIGN) and macrophage mannose receptor (MMR)]. The effect of CA125 antigen on human erythrocytes was determined using solid phase tests and light microscopy. The interaction of CA125 with leukocyte receptors was investigated employing lectin-blot and immunoblot, as well as binding and inhibition solid phase assays. Cancer antigen isolated from human pleural fluid (pfCA125) and pregnancy-associated antigen (pCA125) were included in the glycobiochemical analysis in addition to antigen from the human ovarian carcinoma cell line (clCA125). The results of in silico analysis placed MUC16/CA125 in the context of modular proteins with an annotated role in adhesion-related processes. They pointed to similarities within extracellular serine/threonine rich regions of MUC16 to protein sequences expressed in evolutionarily distant taxa. No relation to annotated domains from available databases appeared, except for BLLF1, a multidomain characteristic of virus envelope glycoproteins of the Herpesviridae family. Bioinformatics analysis also pointed to a possible correlation between functional activities, which are attributed to serine/threonine rich domains of experimental data on the interactions of MUC16/CA125 with specific classes of receptors on cells of the blood system. The modular organization of MUC16/CA125, was analyzed in silico using data taken from the UniProtKB database, which refers to a molecule isolated from the human ovarian cancer cell line, OVCAR-3. Bioinformatic analysis included: determination of homology (using BLAST, Basic Local Alignment Search Tool Tool); investigation of patterns, structural motifs and conserved domains (using databases such as Bgee: a database for Gene Expression and Gene Ontology Evolution, CDD, ELM, BLOCKS, InterProScan and MyHits iProClass); determination of physical and chemical properties, globularity and deviations from the assumed tertiary structure (using ProtParam, ProtScale and GLOBPLOT v2.3 tools); and function prediction using tools that employ several programs: JAFA, ProtFun 2.2 and GeneOntology. Glycobiochemical analysis comprised examination of the influence of CA125 on adhesion and aggregation of erythrocytes, as well as on interactions with different types of leukocyte lectins, namely siglecs [sialic acid-binding immunogobulin (Ig)-like lectin] and C-type lectin-like receptors [selectins, dendritic cell-specific ICAM-3-grabbing non-integrin 1 (DC-SIGN) and macrophage mannose receptor (MMR)]. The effect of CA125 antigen on human erythrocytes was determined using solid phase tests and light microscopy. The interaction of CA125 with leukocyte receptors was investigated employing lectin-blot and immunoblot, as well as binding and inhibition solid phase assays. Cancer antigen isolated from human pleural fluid (pfCA125) and pregnancy-associated antigen (pCA125) were included in the glycobiochemical analysis in addition to antigen from the human ovarian carcinoma cell line (clCA125). The results of in silico analysis placed MUC16/CA125 in the context of modular proteins with an annotated role in adhesion-related processes. They pointed to similarities within extracellular serine/threonine rich regions of MUC16 to protein sequences expressed in evolutionarily distant taxa. No relation to annotated domains from available databases appeared, except for BLLF1, a multidomain characteristic of virus envelope glycoproteins of the Herpesviridae family. Bioinformatics analysis also pointed to a possible correlation between functional activities, which are attributed to serine/threonine rich domains ofproteins identified in the studied taxa, and possible CA125 antigen function. Based on these results, the role of CA125 antigen in adhesion processes could involve interactions through conserved protein sequences responsible for ion transport, and for interactions with sugar substrates. Considering the mucin nature of CA125 antigen, as well as physiological conditions in which its concentration in serum is increased, the effect of this antigen on human erythrocytes was investigated in the first part of glycobiochemical analysis. The results showed that pCA125 and pfCA125 moderately increased aggregation of erythrocytes, and successfully inhibited their adhesion. In contrast, clCA125 showed little to no modulation of these properties. The second part of the glycobiochemical analysis related to interactions with leukocyte receptors. This showed that, as a ligand, CA125 may interact with different types of proteins that bind sialic acid. Siglecs were found to have specific binding patterns, which more effectively distinguished CA125 antigens of fetal from those of cancer origin, in contrast to the binding patterns of sialic acid-specific plant lectins. The most obvious difference was the ligand capacity of pCA125 antigen towards siglec-7, expressed on dendritic cells, NK (natural killer cells), monocytes and CD8+ T cells, and clCA125 towards siglec-9 and siglec-10 on B cells, NK cells, monocytes, neutrophils and CD8+ T cells. Unlike siglecs, all three investigated selectins: L-selectin, E-selectin and P-selectin, interacted in a dose-dependent manner with pfCA125, and to a lesser extent with pCA125, but not with clCA125. Moreover, P-selectin reacted at significantly lower concentrations than L- or E-selectin. Thus, CA125 antigen would preferentially interact with activated endothelial cells or platelets expressing P-selectin, compared to cells expressing the other types of selectin. The interaction of CA125 antigen and DC-SIGN, which is specific for mannan, high-mannose glycans and glycans with terminal Lex / Ley / Lea / Leb antigens was studied. DC-SIGN is expressed on dendritic cells (DC) and recognized pCA125 and pfCA125 antigen. Inhibition of DC-SIGN binding to pCA125 was dependent on the presence of mannose-rich glycans, in contrast to the binding to pfCA125, which was not affected by the presence of N- or O-linked glycans, all which can modify their discrete receptor functions. Macrophage mannose receptor (MMR), which is expressed on macrophages and DC, and which binds terminal mannose, fucose and sialyl Lex, did not react with any of the tested CA125 antigens. C-type lectin-like receptors play an important role in the immune system, mediating in cell-cell interactions, i.e. contacts between leukocytes or between leukocytes and endothelium,and in the binding of pathogens. Glycosylation changes in ligands for C-type lectin-like receptors directly influence their activity and specificity and have important effects on the development, survival and reactivity of cells of the blood and immune systems. Based on the results of this study, differences in the structure/glycosylation of CA125 antigens associated with different physiological or pathological conditions, could alter their influence on the human blood cells, and have important biomedical implications in different microenvironments. Further insight into the nature and mechanisms of CA125 multifunctionality requires an interdisciplinary approach, based on complex interactions that are mediated by its different structural domains. Univerzitet u Beogradu Biološki fakultet Korać, Aleksandra, 1964- Korać, Aleksandra, 1964- Janković, Miroslava Janković, Miroslava Milutinović, Bojana 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=49 https://fedorabg.bg.ac.rs/fedora/get/o:3035/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024527282 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:50 2013-09-30T00:00:00Z 1

Uticaj hroničnog intenzivnog treninga na parametre oksidativnog stresa i masnokiselinski profil plazme i eritrocita kod sportistkinja : doktorska disertacija The effect of chronic intensive training on oxidativ stress parameters and fatty acid profiles of plasma and erythrocytes in female athletes Arsić, Aleksandra Č., 1971- Fosfolipidi, masne kiseline, fizička aktivnost, vaterpolo, fudbal, sportistkinje, slobodni radikali, enzimi antioksidativne zaštite, mononuklearne ćelije Phospholipids, fatty acids, physical activity, water polo, football, female athletes, free radicals, antioxidant enzymes, mononuclear cells Datum odbrane: 10.10.2012. Intenzivna fizička aktivnost utiče na metabolizam lipida i masnih kiselina (MK), dovodi do povećane potrošnje kiseonika u mišićima i drugim tkivima što vodi povećanoj produkciji reaktivnih kiseoničnih vrsta i može uticati na funkciju imunog sistema. Uticaj hroničnog intenzivnog vežbanja na parametre oksidativnog stresa i masnokiselinski profil fosfolipida kod aktivnih sportistkinja nije dovoljno ispitivan. Zbog toga je ova studija imala za cilj da ispita MK profil fosfolipida plazme i eritrocita, parametre oksidativnog stresa, aktivnost enzima antioksidativne zaštite, kao i aktivnost monocita kao dela imunog sistema, kod dve grupe aktivnih sportistkinja: vaterpolistkinja (n=15) i fudbalerki (n=19). Kontrolnu grupu (n=14) su činile zdrave devojke istih godina starosti koje se ne bave fizičkom aktivnošću. Uprkos sličnom dijetarnom unosu, MK profil plazme pokazao je znatno veći udeo stearinske, oleinske i mononezasićenih masnih kiselina (MUFA) i značajno niži procenat ukupnih i n-6 polinezasićenih MK (PUFA) kod fudbalerki u odnosu na vaterpolo i kontrolnu grupu. Sa druge strane vaterpolistkinje su imale višu procentualnu zastupljenost palmitoleinske i arahidonske kiseline u odnosu na kontrolnu grupu. MK profil eritrocita pokazao je značajno veći procenat oleinske kiseline i MUFA kod fudbalerki u odnosu na kontrolnu grupu, i smanjeni procenat stearinske kiseline uz viši udeo palmitinske i palmitoleinske kiseline kod vaterpolistkinja u odnosu na druge dve grupe. Obe grupe sportistkinja su imale značajno niži procenat n-6 PUFA i ukupnih PUFA u poređenju sa kontrolnom grupom. Procenjena aktivnost desaturaza i elongaza u eritrocitima takođe je promenjena kod sportistkinja. Analiza parametara oksidativnog stresa pokazala je značajno veći ukupni antioksidativni status u plazmi i veći stepen lipidne peroksidacije u eritrocitima kod sportistkinja u odnosu na kontrolnu grupu. Koncentracija H2O2 u plazmi bila je veća kod sportistkinja u odnosu na neaktivne žene, ali su fudbalerke imale viši nivo H2O2 i u odnosu na vaterpolistkinje. Sa druge strane, koncentracija O2 .- bila je najniža kod vaterpolistkinja a najviša kod fudbalerki, značajno viša i u odnosu na kontrolnu grupu. Koncentracija NO2 - u plazmi bila je značajno viša kod fudbalerki u odnosu na kontrolnu grupu. Aktivnost enzima antioksidativne zaštite u eritrocitima razlikovala se između sportistkinja i kontrolne grupe. Tako je aktivnost katalaze kod sportistkinja bila značajno viša u odnosu na kontrolnu grupu, dok se aktivnost glutationperoksidaze nije razlikovala između ispitivanih grupa. Aktivnost superoksid-dismutaze bila je najviša kod vaterpolistkinja, i nije se značajno razlikovala između fudbalerki i kontrolne grupe. Analiza metaboličke aktivnosti mononuklearnih ćelija periferne krvi pokazala je veću aktivnost mononuklearnih ćelija kod sportistkinja, dok se produkcija O2 .- i NO2- u mononuklearnim ćelijama nije razlikovala između ispitivanih grupa. Naši rezultati su pokazali da dugotrajna intenzivna fizička aktivnost značajno utiče namasnokiselinski profil fosfolipida plazme i eritrocita, parametre oksidativnog stresa, aktivnost enzima antioksidativne zaštite, menja aktivnost mononuklearnih ćelija periferne krvi ali ne utiče na produkciju O2 .- i NO2 - u mononuklearnim ćelijama. Zapažene razlike između grupa vaterpolistkinja i fudbalerki ukazuju da tip sporta igra značajnu ulogu u promenama u metablizmu kod sportistkinja. Intensive physical activity affects metabolism of lipids and fatty acids (FA), increases consumption of oxygen in muscles and other tissues that leads to increased production of reactive oxygen species and can affect immune system. The effect of chronic intensive exercise on parameters of oxidative stress and phospholipids FA composition in elite female athletes has not been studied extensively so far. Thus the aim of this study was to investigate FA profiles in plasma and erythrocytes phospholipids, parameters of oxidative stress, activity of antioxidative enzyme system and activity of monocytes as a part of immune system in two groups of active female athletes: water polo (n=15) and football (n=19) players. The control group was composed of 14 apparently healthy age-matched sedentary women. In spite of similar dietary patterns, plasma FA profile in the football players showed significantly higher proportion of stearic acid, oleic acid and monounsaturated FA (MUFA), and significantly lower proportion of total and n-6 polyunsaturated FA (PUFA) than the water polo and control group. The water polo players had higher percentages of palmitoleic acid and arachidonic acid than the control subjects. Erythrocyte FA profile differed among groups. We found significantly higher proportion of oleic acid and MUFA in the football group than in the controls, and decreased stearic acid and elevated palmitic and palmitoleic acid in the water polo players than in the other two groups. Both groups of athletes had significantly lower percentages of n-6 PUFA and total PUFA compared to the controls. The estimated activities of elongase and desaturases in erythrocytes were also altered in the athletes. Analysis of oxidative stress parameters showed significantly higher plasma total antioxidant status and higher lipid peroxidation in erythrocytes of the athletes than in the controls. Concentration of H2O2 in plasma was higher in the athletes compared with sedentary women, but also higher in football than in the water polo players. On the other hand, level of O2 .- was the lowest in water polo players and the highest in the football group. Concentrations of both O2 .- and NO2 - were significantly higher in the football than in the control group. Catalase activity was significantly higher in the athletes that in sedentary women, while glutation peroxidase activity was similar in all groups. Superoxide-dismutase activity was higher in the water polo group than in the other two groups. Furthermore, metabolic activity of peripheral blood mononuclear cells was higher in the athletes, and production of O2 .- i NO2 - in mononuclear cells did not differ among the studied groups. Our results have shown that long-term, intense physical training significantly affected FA status of plasma and erythrocyte phospholipids, oxidative stress and antioxidant enzyme activity in women. It also changes metabolic activity of mononuclear cells but not the production of O2 .- i NO2 - in mononuclear cells. The observed differences between the water polo and the football players suggest that the type of regular training may contribute to the altered metabolism in athletes. Key words: phospholipids, fatty acids, physical activity, water polo, football, female athletes Univerzitet u Beogradu Biološki fakultet Korać, Bato. 1962- Korać, Bato. 1962- Vučić, Vesna Vučić, Vesna Glibetić, Marija 1958- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=50 https://fedorabg.bg.ac.rs/fedora/get/o:3038/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024528818 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:51 2013-09-19T00:00:00Z 1

Neuroinflamatorni procesi mozga u amiotrofičnoj lateralnoj sklerozi : studija na modelu hSOD1 G93A pacova Neuroinflammatory processes in the amyotrophic latera sclerosis brain : study of hSOD1 GV3A pacova Bataveljić, Danijela B., 1983- Amiotrofična lateralna skleroza, neuroinflamacija, krvno-moždana barijera, akvaporin-4, ulazni kalijumski ispravljač Amyotrophic lateral sclerosis, neuroinflammation, blood-brain barrier, aquaporin-4, inwardly rectifying potassium channel Datum odbrane: 06.11.2012. Amiotrofična lateralna skleroza (ALS) je neurodegenerativno oboljenje koje pogađa motorne neurone u kičmenoj moždini i višim moždanim centrima. Bolest karakteriše vrlo brza progresija i kratak životni vek od pojave simptoma. Predloženo je više mehanizama koji opisuju patogenezu bolesti, ali je uzrok ALS i dalje nepoznat. Cilj ove studije je da okarakteriše promene u višim moždanim centrima u modelu hSOD1G93A pacova i pokuša da dodatno razjasni mehanizme bolesti. Primenom tehnike magnetno-rezonantnog oslikavanja lokalizovana su neurodegenerativna žarišta u mozgu hSOD1G93A pacova. Istom metodom je in vivo praćena infiltracija T-limfocita pomoću posebno dizajniranih antitela obeleženih ultra malim paramagnetnim partikulama gvožđe oksida. Pokazano je da se CD4+ T-limfociti infiltriraju u tkivo oko moždanih komora, a CD8+ T-limfociti u moždano stablo hSOD1G93A pacova. Praćenje stanja krvno-moždane barijere pomoću Gd-DTPA kontrastnog agensa je ukazalo na njenu narušenost u moždanim regionima gde je uočena infiltracija T-ćelija. Prisustvo aktivirane mikroglije i reaktivnih astrocita je uočeno u moždanom stablu hSOD1G93A pacova. Pored toga, reaktivna mikroglija je uočena u moždanom tkivu oko lateralnih komora i hipokampusu. Nastavci aktivirane mikroglije ostvaruju kontakt sa telom neurona što ukazuje na mogućnost njihove interakcije. Primenom Western blot metode je pokazano da je ekspresija akvaporina-4 (AQP4) povećana, a ulaznog kalijumovog ispravljača (Kir4.1) smanjena u moždanom stablu i moždanoj kori hSOD1G93A pacova. Imunohistohemija na zamrznutim moždanim presecima je pokazala povećanu AQP4 i smanjenu Kir4.1 imunoreaktivnost u nc. facialis, nc. trigeminus i motornoj kori hSOD1G93A pacova. Kada su ispitivani kortikalni astrociti u kulturi, uočena je povećana AQP4 i smnjena Kir4.1 imunoreaktivnost u ALS. Proučavanje funkcionalnih osobina Kir kanala je ukazalo na smanjenu gustinu struja i smanjenu specifičnu membransku provodljivost u ALS astrocitima u kulturi. Pored toga, blokiranje ovih struja dodavanjem 1 mM CsCl ili 100 μM BaCl2 u vanćelijski rastvor je pokazalo da su Cs+-senzitivne odnosno Ba2+-senzitivne struje značajno manje u ALS astrocitima. U ovoj studiji su lokalizovana žarišta neurodegenerativnih i neuroinflamatornih promena u mozgu hSOD1G93A pacova, uočeno je oštećenje krvno-moždane barijere, a posebno su istaknute promene u ekspresiji i funkciji astrocitnih proteina koji doprinose stabilnosti krvno-moždane barijere. Dobijeni podaci su pružili dodatna objašnjenja koja doprinose razumevanju mehanizama ALS. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting lower and upper motor neurons. The disease shows fast progression and short lifetime following the disease onset. Several mechanisms contributing to ALS pathogenesis have been proposed, but the cause of disease remains unclear. The aim of this study was to characterize changes in the upper CNS regions of the hSOD1G93A rat model and to try to clarify disease mechanisms. Foci of neurodegeneration and neuroinflammation were localized in the brain of hSOD1G93A rat using magnetic resonance imaging. The same method was applied for in vivo monitoring of T-lymphocytes infiltration using specifically designed antibodies conjugated with ultrasmall superparamagnetic iron oxide particles. It was shown that CD4+ T-lymphocytes were infiltrated into the brain tissue around lateral ventricles while CD8+ T-lymphocytes were infiltrated into the brainstem of the hSOD1G93A rat. Using Gd-DTPA contrast, it has been shown that the blood-brain barrier was compromised in the brain regions invaded with T-cells. Activated microglia and reactive astrocytes were observed in the brainstem of the hSOD1G93A rat. In addition, reactive microglia was shown in the brain tissue around lateral ventricles and in the hippocampus. Processes of activated microglia were in contact with neuronal somata indicating possible interaction. Western blot results showed increased aquaporin-4 (AQP4) and reduced inwardly rectifying potassium channel (Kir4.1) expression in the brainstem and cortex of the hSOD1G93A rat. Immunohistochemistry on the frozen brain slices showed increased AQP4 and decreased Ki4.1 immunoreactivity in the nc. facialis, nc. trigeminus and motor cortex of the hSOD1G93A rat. Increased AQP4 and decreased Kir4.1 immunoreactivity were retained in cortical ALS astrocytes in culture. Examination of the functional properties of Kir channels revealed a decreased current density and diminished specific membrane conductance in ALS astrocytes in culture. Addition of 1 mM CsCl or 100 μM BaCl2 to the extracellular solution revealed significantly lower Cs+-sensitive and Ba2+-sensitive Kir currents in ALS. In this study we localized and characterized neurodegenerative nad neuroinflammatory changes in the brain of hSOD1G93A rat, confirmed the blood-brain barrier compromise and observed changes in the astrocytic proteins involved in the maintenance of the blood-brain barrier. Obtained data may contribute to further understanding of the mechanisms underlying ALS pathology. Univerzitet u Beogradu Biološki fakultet Anđus, Pavle, 1958- Bačić, Goran, 1951- Božić, Biljana, 1975- Stević, Zorica, 1959- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=51 https://fedorabg.bg.ac.rs/fedora/get/o:3046/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41902607 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:59 2013-01-30T00:00:00Z 1

Značaj fitoplanktona kao indikatora eutrofikacije u akvatorijumu Bokokotorskog zaliva Importance of phytoplankton as indicator of eutrophication in aquatorium of the Boka Kotorska Bay: doctoral dissertation Drakulović, Dragana D., 1978- Fitoplankton, eutrofikacija, indikacija, Bokokotorski zaliv, Crna Gora Phytoplankton, eutrophication, indication, Boka Kotorska Bay, Montenegro Datum odbrane: 10.10.2012. Fitoplanktonski organizmi su primarna karika u lancima ishrane, odnosno primarni producenti organskih supstanci. Sa jedne strane se ističe njihova važnost u ishrani, a sa druge njihov povećan razvoj može da dovede do neželjenih posljedica za ekosistem. Cilj ovog istraživanja je bio da se prikaže kvalitativno i kvantitativno stanje fitoplanktona u Bokokotorskom zalivu, uključujući tu u posljednjem slučaju i biomasu fitoplanktona, a izraženu preko koncentracije hlorofila a. Preko kvalitativnog i kvantitativnog aspekta fitoplanktona može se stvoriti okvirna slika o stepenu eutrofikacije u zalivu i ukazati na moguće opasnosti i mjere koje treba preduzeti da bi se izbjegle negativne posljedice. Sve nabrojane biološke parametre nije moguće odvojiti od fizičko-hemijskih parametara sa kojima su u međusobnoj interakciji i koji direktno utiču na količinu i sastav fitoplanktona. Brojnost fitoplanktona je često dostizala vrijednosti 106 ćelija/l, što je karakteristično za eutrofno područje i nije bila ispod 105 ćelija/l tokom cijelog istraživanja, što opet ukazuje na povećanu eutrofikaciju. Fitoplanktonska grupa koja je dominirala tokom istraživanja su bile dijatomeje, koje su eurivalentna grupa organizama. Druga grupa organizama koja je bila prisutna su dinoflagelate, koje su interesantne s obzirom da mnoge od njih proizvode toksine koji mogu biti štetni za čovjeka. Među dijatomejama zabilježene su vrste koje su karakteristične za područja bogata nutrijentima, što govori o promjenama u zalivu. Alge koje su nađene, a koje preferiraju povećanu količinu nutrijentima su Chaetoceros affinis, Dactyliosolen fragilissimus, Leptocylindrus danicus, Navicula spp., Pseudonitzschia spp., Thalassionema nitzschioides i dr. Analizirani su indeksi diverziteta Shannon-ov indeks diverziteta (H’), recipročan Simpson-ov indeks(1/D) i Margalef-ov indeks (d) za područje Bokokotorskog zaliva i nađeno je da su indeksi bili manji kada je brojnost fitoplanktona bila veća i kada je bila prisutna dominacija određenih vrsta, kao npr. u julu mjesecu kada je dominirala vrsta Thalassionema nitzshioides. To ukazuje na činjenicu da je diverzitet manji kada je prisutna dominacija određenih vrsta. U odnosu na biomasu fitoplanktona izraženu koncentracijom hlorofila a, prema raznim kriterijumima (Håkanson et al., 1994; Ignatiades 2005), zalivsko područje je okarakterisano kao mezo-eutrofno područje. S obzirom da parametri koji pokazuju stepen eutrofikacije ukazuju da Bokokotorski zaliv počinje da dobija karakteristike eutrofnog, treba preduzeti mjere da bi se spriječilo dalje napredovanje prema još višem stepenu eutrofije. Bokokotorski zaliv je jedan osjetljiv ekosistem, a naročito Kotorski zaliv koji je zatvoreniji, sa slabijom dinamikom vodenih masa i pod većim pritiskom eutrofikacije. slabijom dinamikom vodenih masa i pod većim pritiskom eutrofik Phytoplankton organisms are primary link in the food chain and primary producers of organic substances. On one side, it is emphasissed their importance in the diet and, on the other, their excessive growth can lead to undesirable consequences for the ecosystem. The aim of this study is to present qualitative and quantitative situation of phytoplankton in the Boka Kotorska Bay, including in the last case phytoplankton biomass too, which is expressed through the concentration of chlorophyll a. Through qualitative and quantitative aspects of phytoplankton can be create a general overview of the degree of eutrophication in the Bokakotorska Bay and to point out possible hazards and precautions to be taken to avoid negative consequences. All these biological parameters can not be separated from the physical-chemical parameters with which they are in interaction and which directly affect the quantity and qualitative composition of phytoplankton. The abundance of phytoplankton often reached values of 106 cells/l, which is typical for an eutrophic area and abundance of phytoplankton wasn’t below 105 cells/l throughout the study, which again points to increased eutrophication. Phytoplankton group that has dominated almost during all investigated period were diatoms, which are eurivalent group of organisms. Another group of organisms that were present were dinoflagellates, which are interesting because they produce toxins that can be harmful to humans. Among diatoms, it was found algae that are otherwise characteristic of nutrients-enriched areas, which indicate changes in the Bay. Noticed algae that prefer higher nutrients concentration were Chaetoceros affinis, Dactyliosolen fragilissimus, Leptocylindrus danicus, Navicula spp., Pseudo-nitzschia spp. and Thalassionema nitzschioides. The following diversity were analyzed: Shannon's diversity index (H '), the reciprocal of Simpson's index (1 / D) and Margalef's index (d) for the Boka Kotorska Bay. It was found that indices were lower when phytoplankton abundance was higher and when the dominance of certain species was noticed, such in current study it was in July, when dominated species Thalassionema nitzshioides. That suggests that diversity is lower when occurrs predominance of certain species. In relation to phytoplankton biomass expressed in chlorophyll a concentration, according to various criteria (Håkanson et al., 1994; Ignatiades 2005), Boka Kotorska Bay was identified as meso-eutrophic area. Considering that parameters which indicate the degree of eutrophication suggest that the Boka Kotorska Bay begins to take characteristic of eutrophic area, it should be taken measures to prevent further progression to an even higher degree of eutrophication. Boka Kotorska Bay is one particularly sensitive ecosystem, especially the Kotor Bay, which is closed and with the weaker dynamics of water masses and under the growing pressure of eutrophication. Univerzitet u Beogradu Biološki fakultet Cvijan, Mirko Cvijan, Mirko, Vuksanović, Nenad Krizmanić, Jelena Krivokapić, Slađana 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=59 https://fedorabg.bg.ac.rs/fedora/get/o:3366/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41904655 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:62 2013-01-31T00:00:00Z 1

Paleoekologija karbonskih drvenastih prečica reda Lepidodendrales sa posebnim osvrtom na region Balkanskog poluostrva Paleoecology of carboniferous arboreous Lycopsids from order Lepidodendrales with special consideration of region of Balkan peninsula : doctoral dissertation Đorđević-Milutinović, Desa Đ., 1967- Lepidodendron, Lepidophloios, Sigillaria, Diaphorodendron, Synchyidendron, karbon, ugalj, paleobotanika, paleoekvator Lepidodendron, Lepidophloios, Sigillaria, Diaphorodendron, Synchyidendron, Carboniferous, coal, paleobotany, paleoequator Datum odbrane: 2.10.2012. Tokom perioda karbona, od pre 320 do pre 306 mliona godina, u području tropskog pojasa (paleoekvatora) Evroameričkog kopna, razvijale su se močvarne šume čiji su edifikatori bile drvolike prečice reda Lepidodendrales. Prečice generalno pripadaju razdelu Lycopodiophyta i predstavljaju jednu od najstarijih grupa biljaka, čija evolutivna linija traje sve do današnjih dana. Njihovi najstariji predstavnici Asteroxylon, .Drepanophycus i Baragwanathia pojavili su se pre oko 400 miliona godina i spadaju u grupu prvih kopnenih biljaka. Pored toga Lycopodiophyta su evolitivno bile i prve biljke koje su formirale fanerofitnu životnu formu (rodovi Cyclostigma i Archaeosigillaria u gornjem devonu pre 370 miliona godina). Tokom karbona, drvolike prečice su dostigle svoj maksimalan razvoj. U to vreme veliki prostori paleotropskog pojasa bili su prekriveni močvarnim šumama u kojima su dominirale Lycopodiophyta čija su stabla prevazilazila 40 metara visine. Najveći broj karbonskih prečica pripadao je redu Lepidodendrales i rodovima Lepidodendron, Synchysidendron, Diaphorodendron, Lepidophloios i Sigillaria. Krajem karbona, pre oko 300 miliona godina sve drvolike prečice su izumrle, i koliko je za sada poznato, u okviru ovog razdela više se nisu pojavljivale drvolike životne forme. Danas predstavnici Lycopodiophyta predstavljaju marginalnu grupu biljaka, minorne uloge i značaja u okviru različitih vegetacija, čiji predstavnici (Lycopodium, Selaginella, Isoetes i dr.) nemaju gotovo nikakvih morfoloških sličnosti sa predstavnicima iz reda Lepidodendrales. Najveći deo uporedne analize izmedju Lepidodendrales i recentne denroflore bio je baziran prvenstveno na principima aktuelizma i zakonitostima koje se javljaju prilikom fosilizacije biljaka. Aktuelističke metode su primenjene zato što je utvrdjeno da postoje bazične sličnosti u razvoju vegetacija gornjeg karbona i neogena/kvartara. Tu prvenstveno treba pomenuti pojedine uticaje/dogadjaje koji su doveli do formiranja i diferenciranja različitih vegetacijskih pojaseva, kao što su pojava Karbonskog i Pleistocenskog ledenog doba, nastanak intenzivnih orogeneza (Hercinsko/Varscinska i Alpijska), formiranje sličnih močvarnih staništa, postojanje tropskog vegetacijskog pojasa, kao i činjenica da su karbonske kao i neogene močvarne šume ostavile za sobom izrazito velike količine uglja. Paleotropske šume u kojima su dominirale drvolike prečice reda Lepidodendrales predstavljaju izuzetno značajnu i na osnovu fosila veoma dobro dokumentovanu šumsku vegetaciju čiji se kompleksni ekološki značaj može sagledati u sledećem: 1. Neobnovljivi energetski resursi sadržani u ogromnim količinama karbonskog uglja koji je nastao uglavnom od stabala Lepidodendrales. 2. Konvergentne morfo-anatomske karakteristike sa filogenetski udaljenim kopnenim (vaskularnih) semenim biljakama (drvoliki habitus, tipovi grananja, strukture slične semenima, pojava monokarpije). To ukazuje da su se mnoge krakteristike biljaka, kao i životne forme (u ovom slučaju fanerofitna) pojavljivale nezavisno i više puta u filogenetski udaljenim evolutivnim linijama. 3. Tek sa formiranjem i razvojem bujnih paleotropskih šuma došlo je, zahvaljujući povoljnoj šumskoj mikroklimi, pogodnim staništima i gotovo neograničenom izvoru hrane, do ubrzanog razvoja kopnenih životinja. U cilju objašnjenja razvoja i dinamike ovih šuma analizirane su paleoekološke osobine pojedinih rodova koji su bili njihovi edifikatori. Kao referentni rodovi uzeti su oni za koje postoji najviše fosilnih i literaturnih podataka i koji su već ranije utvrdjeni kao morfotipovi, kao što su Lepidodendron, Synchysidendron, Diaphorodendron, Lepidophloios i Sigillaria. Ovi rodovi su svojim morfoanatomskim karakteristikama, prvenstveno opštim izgledom habitusa, tipom grananja, visinom stabala i odlikama korenskog sistema uporedjivani sa strukturnim karakterisitkama recetnih predstavnika dendroflore, pre svega sa drvećem i drvenastim semenim biljkama. Na osnovu pojave i uloge sličnih ili različitih morfo-anatomskih karakteristka kod ispitivanih fosilnih Lepidodendrales i referentnih predstavnika recentne dendroflore utvrdjene su brojne konvergetne strukturne karakteristike koje objašnjavaju paleoekološki karakter i značaj izumrlih Lepidodendrales. Prilikom analize opšteg izgleda habitusa i visine stabala utvrdjeno je da su monokarpne vrste, posebno rod Lepidodendron, mogle da budu visoke i preko 40 m (koliko je za sada utvrdjena najveća visina ovog roda), što ukauje da su neki predstavnici Lepidodendrales visinom približavali recentnim četinarima, odnosno da su bili viši od mnogih današnjih drvenastih cvetnica. Konstatovane su analogne heteroblastične i monokarpne odlike vegetativnih i reproduktivnih adultnih stadijuma predstavnika drevnih rodova Lepidodendron, Synchysidendron i Lepidophloios i recentnih monokarpnih vrsta iz familija Agavaceae, Bromelidaceae i Asteraceae. Monokarpni Lepidodendrales pokazuju određenu sličnost sa nekim džinovskim rozetastim (zeljastim) monokarpnim vrstama roda Agave koje upadljivo, heteroblastično, menjaju izgled habitusa tokom reproduktivnog stadijuma. Pored toga, monokarni predstavnici Lepidodendrales se opstajanjem na staništu i posle reproduktivne faze mogu porediti sa drvenastim monokarpnim vrstama roda Tachigali kod kojih nema heteroblastičnih promena, ali koje se, takođe zadržavaju na staništu još izvesno vreme posle reproduktivne faze, obezbedjujući svojim stablom prostor mladim jedinkama iste vrste. Uočena je i sličnost heteroblastičnih promena tokom smenjivanja vegetativnog u reproduktivni stadijum kod Lepidodendrales i prelaza iz juvenilnog u adultni stadijum recentnih polikarpnih vrsta roda Pseudopanax. Uporedne analize bazirane na gradji i ulozi listova i lisnih jastučića dovele su do zaključka da su listovi Lepidodendrales, koji periodično opadaju ostavljajući za sobom lisne baze (lisne jastučiće), jedinstvena karakteristika reda Lepidodendrales i da se ne mogu definitivno porediti sa recentnim biljkama. Nasuprot tome, postoje izvesne analogne morfološke odlike osnovnih delova lista, pre svega lisne ploče i ligule Lepidodendrales i nekih recentnih biljaka. Na poprečnom preseku lisna ploča Lepidodendrales slična je lisnoj ploči nekih vrsta roda Pinus iz grupe Diploxylon, odnosno vrstama iz grupe Haploxylon. Donekle se i ligula Lepidodendrales može porediti sa ligulom kod familije Poaceae, pre svega u pogledu sličnog položaja - u pazuhu lista, tj na prelazu lisne sare u lisnu ploču. Rizomorfni ili korenski sitem Lepidodendrales označen kao stigmarija (rod Stigmaria) može se uporediti sa korenovima nekih drvenastih recentnih biljaka sa vlažnih i močvarnih staništa. Naime, može se pretpostaviti da su bočni korenski izdanci stigmarija imali aeracionu ulogu slično pneumatoforama na korenovima današnjih vrsta iz rodova Taxodium, Nyssa, ili mangrova vegetacija (Rhizophora spp.). Na osnovu velikog broja fosilnih ostataka zaključeno je da su stigmarije bile površinski organi ili površinski deo korenskog sistema čiji se podzemni deo, poput drugih podzemnih biljnih organa, nije sačuvao u fosilnom obliku. U doktorskoj disertaciji je obavljena i uporedna analiza paleotropskih šuma Lepidodendrales i odgovarajućih recentnih šumskih zajednica. Utvrdjeno je da paleotropske šume najviše sličnosti pokazuju sa suptropskim močvarnim šumama u kojima dominira močvarni četinar Taxodium spp. Obe ove, vremenski veoma udaljene, zajednice odlikuje slično močvarno stanište, kao i sličan nasumičan raspored i opšti izgled edifirkatorskih vrsta, najveći deo fitomase se nalazi u stablu, dok je veličina krošnji zanemarljiva. Paleotropske močvarne šume se mogu porediti i sa recentnim tropskim kišnim šumama, pre svega stoga što se obe zajednice razvijaju u uslovima vlažne tropske klime. Međutim, mora se uzeti u obzir da struktura recentnih tropskih šuma daleko složenija zahvaljujući raznovrsnim životnim formama koje su razvile različite vrste cvetnica. Diskutovana je i izvesna analogija paleotropskih šuma Lepidodendrales i borealnih četinarskih šuma - tajgi, koja se ogleda u maloj taksonomskoj raznovrsnosti i malom broju edifikatorskih vrsta. U disertaciji su po prvi put iscrpno komentarisana dosadašnja istraživanja Lepidodendrales na Balkanskom poluostrvu. Na osnovu dostupnih podataka florističkih spiskova i paleofitocenoloških podataka većeg broja različitih paleotropskih zajednica Lepidodendrales na području zapadnog i centralnog Balkana, na teritoriji današnjih država Slovenije, Bosne i Hercegovine i Srbije, uradjena je rekonstrukcija mogućeg/pretpostavljenog staništa odgovarajućih paleofitocenoza. During the Carboniferous period, 320-306 million years ago, swamp forests with tree-like lycopsids named Lepidodendrales as edificatory species have developed in the region of tropical belt (paleoequator). The lycopsids belong to the general division of Lycopodiophyta, representing one of the oldest plant groups, and their evolution continues to this day. The oldest lycopsids have appeared about 400 million years ago and their representatives from genera Asteroxylon, Drepanophycus and Baragwanathia belong to the group of first land plants. Lycopodiophyta were also the first land plants to form the phanerophyte life form (genera Cyclostigma and Archaeosigillaria in Upper Devonian, 370 million years ago). During the Carboniferous period, the arboreous lycopsids have reached their maximal development. At that time there were large areas of paleotropical belt covered in swamp forests, where the edificatory species were Lycopodiophyta over 40 m tall. The Carboniferous arboreous lycopsids belonged to order Lepidodendrales and genera Lepidodendron, Synchysidendron, Diaphorodendron, Lepidophloios and Sigillaria. By the end of Carboniferous (about 300 million years ago) all the arboreous lycopsids became extinct, and according to present knowledge the tree-like life forms never appeared again in this group. Today the representatives of Lycopodiophyta are a marginal group of plants, with a minor role and importance in various vegetation lists. Their representatives (Lycopodium, Selaginella, Isoetes etc.) have almost no morphological similarities with the arboreous lycopsids of order Lepidodendrales. The comparative analysis of Lepidodendrales and the recent dendroflora was mostly based on principles of actualism and rules of plant fossilization. The actualistic methods were applied as some basic similarities were noted in development of vegetation in Upper Carboniferous and Neogene/Quaternary. It is particularly important to mention certain factors/events that led to formation and differentiation of different vegetation belts. They include appearance of Carboniferous and Pleistocene Ice Ages, appearance of intensive orogeny (Hercynian/Variscan and Alpine), formation of similar wetland habitats, presence of a tropical vegetation belt, as well as the fact that Carboniferous and Neogene swamp forests have both left behind prominent large amounts of coal. The paleotropical forests dominated by tree-like lycopsids of order Lepidodendrales are representative of particularly important forest vegetation, well-documented by fossils. Its complex ecological importance may be summed in a following way: 1. Unsustainable energetic resources of enormous amounts of Carboniferous coal, mostly originating from stems of Lepidodendrales. 2. Morpho-anatomic characteristics convergent with those of phylogenetically distant land (vascular) seed plants (tree-like habit, branching types, seed-like structures, appearance of monocarpy). This indicates that many of the plant characteristics and life forms (in this case phanerophytes) have appeared independently several times in phylogenetically distant evolutionary lines. 3. The accelerated development of land animals took place only after the formation and development of lush paleotropical forests and appearance of favorable forest microclimates, suitable habitats and almost infinite sources of food. In order to explain development and dynamics of these forests, paleoecological characteristics of certain edificatory genera were analyzed. The reference genera were chosen by number of fossil and literature data and by being previously determined as morphotypes, for example Lepidodendron, Synchysidendron, Diaphorodendron, Lepidophloios and Sigillaria. These genera were compared with structural characteristics of recent representatives of dendroflora, primarily trees and woody seed plants, regarding the general habit, type of branching, height of habit/stem and characteristics of root system. Appearance and role of similar or different morpho-anatomical characteristics in studied fossil Lepidodendrales and referenced representatives of recent dendroflora were used to determine numerous convergent structural characteristics explaining the paleoecological character and importance of extinct Lepidodendrales During the analysis of general habit and height of trees, it was determined that the monocarpous species, particularly the genus Lepidodendron, could reach over 40 m in height (that is the greatest determined height of this genus so far), indicating that certain representatives of Lepidodendrales could reach the height of recent conifers and were taller than many present-day arboreous flowering plants. Analogous heteroblastic and monocarpous characteristics of vegetative and reproductive adult stages were recorded in representatives of ancient genera Lepidodendron, Synchysidendron and Lepidophloios and in recent monocarpous species from families Agavaceae, Bromelidaceae and Asteraceae. The monocarpous Lepidodendrales are showing certain similarities with some giant rosette-bearing (herbaceous) monocarpous plants of genus Agave, which have a pronounced heteroblastic change in habitus during the reproductive stage. As monocarpous representatives of Lepidodendrales remain in the habitat after the reproductive phase, they may also be compared with arboreous monocarpous species of genus Tachigali, which lack the heteroblastic changes but also remain in the habitat for some time after the reproductive phase, providing shelter for young individuals of its species with its stem. Also noted was similarity of heteroblastic changes during the shift from the vegetative to the reproductive stage in Lepidodendrales and shift from the juvenile to the adult stage in recent polycarpous species of genus Pseudopanax. The comparative analyses based on structure and role of leaves and leaf cushions led to conclusion that leaves of Lepidodendrales, periodically excised while leaving leaf bases (cushions) on the stem, are a unique characteristic of order Lepidodendrales and may not be definitively compared with recent plants. On the other hand, there are certain analogous morphological characteristics of main flower parts, primarily the leaf plate and ligula in Lepidodendrales and certain recent plants. The transversal cut of leaf plate of Lepidodendrales is similar to that of certain species of Pinus from Diploxylon group or species from Haploxylon group. The ligula of Lepidodendrales may be compared to some extent to ligula in family Poaceae, primarily due to the similar position – between the leaf and the stem, at the transition between the leaf sheath and blade. The rhizomorph or root system of Lepidodendrales named stigmaria (genus Stigmaria) may be compared with roots of certain recent woody plants from wetland and marsh habitats. It may be assumed that the lateral root shoots of stigmaria had a role in aeration, similar to pneumatophores in roots of present-day species from genera Taxodium, Nyssa, or mangrove vegetation (Rhizophora spp.). In relation to the large number of fossil remains it was concluded that stigmaria were aerial organs or aerial parts of root system, while the underground part, like many other underground plant organs, was not preserved in fossil form. The Ph.D. thesis also includes a comparative analysis of paleotropical forests of Lepidodendrales and corresponding recent forest associations. It was determined that the paleotropical forests show most similarities with the subtropical swamp forests dominated by swamp conifer Taxodium spp. Both these associations, although very distant from each other in time, are characterized by similar swamp soil and similar random distribution and general habitus of edificatory species – the greatest part of phytomass is situated in the bole while the canopy size is negligible. The paleotropical swamp forests may also be compared to the recent tropical rainforests, as both associations develop in conditions of humid tropical climate. However, it must be considered that the structure of recent tropical forest is far more complex due to diverse life forms developed by various species of flowering plants. Also discussed was certain analogy between the paleotropical forests of Lepidodendrales and boreal conifer forest (taiga), expressed in low taxonomic diversity and a small number of edificatory species. This dissertation is the first paper with detailed analysis of all studies on Lepidodendrales performed at Balkan Peninsula. The available data in floristic lists and paleophytocoenological data on a larger number of different paleotropical associations of Lepidodendrales in western and central parts of Balkans (the territories of present-day Slovenia, Bosnia-Herzegovina and Serbia) were used for reconstruction of possible/assumed habitat of appropriate paleophytocoenoses. Univerzitet u Beogradu Biološki fakultet Stevanović, Vladimir Stevanović, Branka Sudar, Milan Kolar-Jurkovšek, Tea 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=62 https://fedorabg.bg.ac.rs/fedora/get/o:3372/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41904911 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:63 2013-02-01T00:00:00Z 1

Taksonomsko-faunistička studija leptira (Insecta : Lepidoptera) Fruške Gore Taxonomic-faunistical study of butterflies and moths (Insecta : Lepidoptera) of mt. Fruška Gora : doctoral dissertation Stojanović, Dejan V. 1966- Lepidoptera, Fruška gora, fauna Lepidoptera, Mt. Fruška Gora, fauna Datum odbrane: 7.12.2012. U studiji je dat prikaz jedanaestogodišnjih istraţivanja insekata iz reda Lepidoptera na Fruškoj gori. Registrovane su 934 vrste leptira i moljaca. Za 382 vrste Lepidoptera ili 40,89% od ukupnog broja vrsta izvršena je taksonomska verifikacija analizom hitinskih armatura genitalnih aparata. U periodu od 2001. do 2011. godine sakupljani su leptiri i moljci uglavnom uz pomoć svetlosne klopke (ţivine sijalice TEŢ WTF od 250 W, “Philips Ml“ od 100, 160, 250 i 400 W i petromaks lampe od 400 W), iza koje je postavljeno belo pamuĉno platno. 934 zabeleţene vrste su svrstane u 22 superfamilije, 47 familija i 564 rodova. Broj od 934 vrste Lepidoptera predstavlja u odnosu na evropsku faunu leptira (8478 vrsta) 11,01%. Sve vrste leptira i moljaca Fruške gore svrstane su u 7 zoogeografskih kategorija. PreovlaĊuju evroazijske vrste (449 vrsta ili 48,07% od ukupnog broja vrsta). Evropskih vrsta je 236 (25,27% od ukupnog broja vrsta). Mediteransko-azijski elementi su zastupljeni sa 162 vrste ili 17,34% od ukupnog broja vrsta. Holarktiĉki elementi zastupljeni su sa 44 vrste ili sa 4,71% od ukupnog broja vrsta, a palearktiĉki sa 25 vrsta ili 2,68% od ukupnog broja vrsta. Paleotropsko-suptropski elementi zastupljeni su sa 10 vrsta ili sa 1,07% od ukupnog broja vrsta. Kosmopolitskih vrsta je 8 vrsta ili 0,86% od ukupnog broja vrsta. Sve evidentirane vrste u ovoj studiji grupisane su u pet skupova: mali moljci, veliki moljci, dnevni leptiri, zemljomerke i sovice. Ukupno 287 vrsta malih moljaca svrstano je u 16 superfamilija i 31 familiju. Više od 5% vrsta malih moljaca Evrope (5,16%) je zastupljeno na Fruškoj gori. Veliki moljci (Lasiocampidae, Saturniidae, Sphingidae, Drepanidae, Notodontidae, Lymantriidae i Arctiidae) su zastupljeni na Fruškoj gori sa 77 vrsta . Više od ĉetvrtine vrsta velikih moljaca Evrope (27,5%) je zastupljeno na Fruškoj gori. Dnevni leptiri (Hesperiidae, Papilionidae, Pieridae, Lycaenidae i Nymphalidae) su zastupljeni na Fruškoj gori sa 115 vrsta. Više od ĉetvrtine vrsta dnevnih leptira Evrope (26,13%) je zastupljeno na Fruškoj gori. Zemljomerke su zastupljene na Fruškoj gori sa 187 vrsta. Oko petine vrsta zemljomerki Evrope (20,43%) je zastupljeno na Fruškoj gori. Sovice (Noctuidae, Pantheidae, Nolidae) su zastupljene na Fruškoj gori sa 268 vrsta. Više od petine vrsta sovica Evrope (20,87%) je zastupljeno na Fruškoj gori. Najbrojnija je grupa malih moljaca sa 287 zabeleţenih vrsta ili sa 30,73% od ukupnog broja utvrĊenih vrsta. Zatim sledi grupa sovica sa 268 zabeleţenih vrsta ili 28,69% od ukupnog broja utvrĊenih vrsta. Na trećem mestu po zastupljenosti nalazi se grupa zemljomerki sa 187 zabeleţenih vrsta ili sa 20,02% od ukupnog broja utvrĊenih vrsta. Slede dnevni leptiri (sa 115 vrsta ili 12,31% od ukupnog broja vrsta) i veliki moljci (sa 77 vrsta ili 8,24% od ukupnog broja vrsta). Na Fruškoj gori je zabeleţeno 129 vrsta Lepidoptera (13,80% od ukupnog broja vrsta) koje mogu naneti štetu lišćarskom i ĉetinarskom drveću. Istraţivanjima na Fruškoj gori identifikovana je 61 vrsta Lepidoptera iz grupe migratornih vrsta, tj. selica. Sezonskih selica prvog reda ima 7 vrsta, sezonskih selica drugog reda 1 vrsta, selica iseljenika (lokalnih selaca prvog i drugog reda) 36 vrsta, selica raseljenika (povremenih selaca) 10 vrsta, selica raseljenika (vrsta koje proširuju svoj areal) 2 vrste, dok mogućih selica ima 5 vrsta. U odnosu na zabeleţeni broj od 934 vrste leptira, procenjuje se da je poznato svega oko jedne trećine vrsta koje bi se mogle otkriti na Fruškoj gori. PronaĊene su 133 nove vrste iz reda Lepidoptera za faunu Srbije. Prvi put u Srbiji, ali i u zemljama u sastavu bivše SFRJ je kao prilog poznavanju faune Lepidoptera u ovoj studiji dat detaljan prikaz hitinskih armatura genitalnih aparata sa opredeljujućim taksonomskim karakteristikama za 250 vrsta (26,76% od ukupnog broja vrsta) uglavnom iz grupe malih moljaca i za nekoliko izdvojenih taksona ostalih grupa. Dat je uporedni prikaz brojnosti vrsta po familijama i superfamilijama za Frušku goru, Timoĉku krajinu, Evropu, Rumuniju, rumunski Banat i MaĊarsku. Lepidoptera su veoma slabo istraţeni na pojedinim podruĉjima Fruške gore. Ovo se prvenstveno odnosi na podruĉje juţno od Dunava oko Neština, Suseka, Banoštora i Ĉerevića, deo od Sremskih Karlovaca do Petrovaradina i Ĉortanovaca, od Krušedola i Neradina do Iriga sa juţne strane Fruške gore i od Vrdnika do Leţimira sa jugozapadne strane (izuzimajući podruĉje oko grgurevaĉkog lovaĉkog doma, selo Grgurevci). Neophodno je da se faunistiĉka i ekološka istraţivanja nastave. Veliki broj lokaliteta je nedovoljno istraţen, na pojedinim mikrolokalitetima istraţivanja nisu ni otpoĉela, a potencijalno su na njima se mogu naći zanimljivi nalazi. This thesis presents results of an eleven-year research on insects belonging from order Lepidoptera on Mt. Fruška Gora. Total of 934 species were recorded. For 382 species Lepidoptera, or 40.89% of the total number of species, a taxonomic verification has been performed by the analysis of chitinous armatures of genital apparatus. In the 2001-2011 period, the specimens were collected mostly by light trap (mercury bulb TEŢ WTF of 250W, “Philips Ml“ of 100, 160, 250 and 400W, and Petromax lamp of 400W), with a white cotton sheet propped in behind. 934 recorded species of Lepidoptera belong to 22 superfamilies, 47 families and 564 genera. The number of 934 species represents 11,01% of European fauna of Lepidoptera (8,478 species). The Lepidoptera species from Mt. Fruška Gora are classified into seven zoogeographical categories. Eurasian species are prevailing (449 species or 48.07% of the total number of species). We recorded 236 European species (25.27% of the total number of species) and 162 Mediterranean-Asian species (17.34% of the total number of species). Holarctic elements are represented by 44 species (4.71% of the total number of species), Palearctic elements by 25 species (2.68% of the total number of species), while Paleotropical-subtropical elements are represented by 10 species (1.07% of the total number of species). Finally, cosmopolitan elements are represented by eight species (0.86% of the total number of species). Within the research, all registered species were classified into five groups: Microlepidoptera (micromoths), macromoths, butterflies, geometrid moths and owlet moths. 287 species of micromoths are classified into 16 superfamilies and 31 families. More than 5% of European species of micromoths (5.16%) are present on Mt. Fruška Gora. Macromoths (Lasiocampidae, Saturniidae, Sphingidae, Drepanidae, Notodontidae, Lymantriidae and Arctiidae) are represented on Mt. Fruška Gora with 77 species. More than one quarter of European species of macromoths (27.5%) are recorded on Mt. Fruška Gora. Butterflies (Hesperiidae, Papilionidae, Pieridae, Lycaenidae and Nymphalidae) are represented on Mt. Fruška Gora with 115 species, which is more than a quarter of the butterfly species of Europe (26.13%). Geometrid moths are represented by 187 species on Mt. Fruška Gora, which is about one fifth of European species of Geometridae (20.43%). Owlet moths (Noctuidae, Pantheidae and Nolidae) are represented on Mt. Fruška Gora by 268 species, which is more than a fifth of the European owlet moth species (20.87%). The micromoths are the most numerous group with 287 recorded species, or 30.73% of the total number of species recorded on Mt. Fruška Gora. They are followed by the group of owlet moths with 268 recorded species (28.69% of the total number of species), geometrid moths with 187 recorded species (20.02% of the total number of species), butterflies (with 115 species or 12.31% of the total number of species), and macromoths (with 77 species or 8.24% of the total number of species). Of all Lepidoptera species recorded in Mt. Fruška Gora, 129 (or 13.80% of the total number of species) may be harmful for deciduous and coniferous trees. Research also revealed 61 species of Lepidoptera belonging to the group of migratory species. Seven species are first-order seasonal migratory species (eumigrators), one seasonal species is second-order migratory species (paramigrator), and 36 species are emigrants (first- and second-order local migrants). Finally, among the dismigrators there are two invasive species that expand their areas and five species that are possibly migratory. Regarding the recorded number of 934 species of Lepidoptera, it is estimated that this is just one third of the species that might exist on Mt. Fruška Gora and the rest could be recorded in the future. From Lepidoptera species recorded, 133 are new for the fauna of Serbia. For the first time in Serbia, but also in other former Yugoslav countries, a detailed analysis of chitinous armatures of genital apparatus with presenting specific taxonomic characteristics for 250 species (26.76% of the total number of recorded species), mostly for micromoths and some selected taxa. A comparative overview is given of species population number within families and superfamilies in investigated Fruška Gora area, as well as for Timoĉka Krajina, Europe, Romania, Romanian Banat, and Hungary. The order Lepidoptera is not sufficiently investigated in some areas of Mt. Fruška Gora. This primarily refers to the area south of the Danube River around Neštin, Susek, Banoštor, and Ĉerević, to the part between Sremski Karlovci, Petrovaradin and Ĉortanovci, from Krušedol and Neradin to Irig on the south slope of Mt. Fruška Gora, and from Vrdnik to Leţimir on the southwest slope (except the area around hunter’s house in the village of Grgurevci). Therefore, it is necessary to continue further faunistic and ecological research. A large number of localities are not explored enough, while at some microlocalities investigations have not even started, although they could be very interesting with possible new findings. Univerzitet u Beogradu Biološki fakultet Ćurčić, Srećko Stanisavljević, Ljubiša Kereši, Tatjana Pešić, Vladimir Ćurčić, Srećko 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=63 https://fedorabg.bg.ac.rs/fedora/get/o:3424/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024543410 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:64 2013-02-06T00:00:00Z 1

Efekti i mehanizmi delovanja interleukina-17 na funkcije mezenhimskih i endotelskih ćelija Effects of interleukin-17 on mesenchymal and endothelial cell functions and mechanisms involved : doctoral dissertation Kocić, Jelena S. 1981- Interleukin-17, mezenhimske matične ćelije, endotelske ćelije, diferencijacija, angiogeneza, C2C12, EA.hy 926, tkivo pupčanika, hipoksija Interleukin-17, mesenchymal stem cells, endothelial cells, differentiation, angiogenesis, C2C12, EA.hy 926, umbilical cord, hypoxia Datum odbrane: 1.10.2012. Interleukin (IL) 17 familija citokina se smatra najmanje istraženom citokinskom familijom sa značajnom ulogom u procesu inflamacije. Ubikvitarna rasprostranjenost receptora za IL-17 omogućava ovom citokinu mnogobrojne biološke efekte u organizmu, poput važne uloge u imunskom odgovoru i regulaciji procesa hematopoeze, ali i u progresiji različitih bolesti, uključujući inflamatorna, autoimunska i maligna oboljenja. IL-17 ima ulogu u ćelijskim procesima poput proliferacije i diferencijacije, i to prvenstveno na hematopoetskim matičnim i progenitor ćelijama, pri čemu IL-17 ispoljava različite efekte na proliferaciju i diferencijaciju zavisno od tipa ćelijske loze i stepena diferencijacije ćelija. Takoñe, zbog ubikvitarne rasprostranjenosti svog receptora, IL-17 je uključen u interakcije izmeñu imunskog sistema i somatskih tkiva. Novija istraživanja su pokazala da IL-17 ima i ulogu finog regulatora diferencijacije mezenhimskih matičnih ćelija (MSC, Mesenchymal stem cells), s obzirom na to da stimuliše osteogenu diferencijaciju dok, s druge strane, inhibira adipogenu diferencijciju humanih MSC. Savremena istraživanja biologije MSC ukazala su na širok opseg njihove potencijalne terapijske primene, prvenstveno u regenerativnoj medicini, jer ove multipotentne adultne matične ćelije koje predstavljaju nediferencirane ćelije sa sposobnošću samoobnove, imaju sposobnost diferenciranja u ćelije tkiva mezenhimskog porekla, poput osteoblasta, hondroblasta i adipocita, a prema saznanjima koja imamo danas, i u ćelije tkiva ektodermalnog i endodermalnog porekla. Matične ćelije različitog stepena multipotentnosti izolovane su iz raznih adultnih tkiva, kao i perinatalnih tkiva koja se poslednjih godina sve češće pominju kao povoljan izvor MSC. Meñutim, i pored velikog napretka u ovoj oblasti, nema konačnih saznanja kako o mehanizmima odgovornim za regulaciju višestrukih funkcija MSC, tako i o njihovom ukupnom terapijskom potencijalu. Kako biološke funkcije MSC umnogome zavise od konteksta mikrosredine, ispitivanje interakcija MSC i IL-17 u održavanju multipotentnosti, mobilizaciji i usmerenoj diferencijaciji MSC je od posebnog značaja. Pored mezenhimskih ćelija, IL-17 ostvaruje svoje efekte delovanjem na endotelske ćelije. Jedan od terapijskih ciljeva u regenerativnoj medicini, koji je još uvek nedovoljno objašnjen, je i podsticanje revaskularizacije oštećenog tkiva. Stimulacija postojećih, in situ prisutnih endotelskih ćelija na angiogenezu je jedan od mogućih mehanizama. Efekti IL-17 na endotelske ćelije nisu do sada u potpunosti opisani, i poznato je samo da IL-17 u prisustvu drugih poznatih angiogenih faktora stimuliše sposobnost endotelskih ćelija za angiogenezu. Pored toga, poznato je da se funkcije ćelija kao i delovanje citokina značajano razlikuju u zavisnosti od procenta kiseonika prisutnog u mikrosredini ćelija. Efekat delovanja IL-17 na endotelske ćelije u prisustvu različitih koncentracija kiseonika do sada nije istraživan. Takoñe je još uvek nepoznato da li IL-17 može uticati na diferencijaciju MSC u endotelske ćelije. Da bi se sprovela istraživanja u ovom pravcu, neophodno je uspostaviti pogodan model za diferencijaciju MSC u endotelske ćelije Cilj istraživanja ove disertacije bilo je ispitivanje efekata IL-17 na različite ćelijske funkcije mezenhimskih i endotelskih ćelija u specifičnim uslovima mikrosredine. Analizirano je dejstvo IL-17 na proliferaciju, migraciju, angiogenezu i diferencijaciju ćelija. Istraživani su i molekularni mehanizmi koji omogućavaju finu regulaciju ćelijskih funkcija od strane IL-17, analizom aktivacije signalnih molekula, kao i ekspresije gena i proteina neophodnih za specifične funkcije. Posebna pažnja u istraživanjima bila je posvećena izolaciji, karakterizaciji i endotelskoj diferencijaciji primarnih MSC iz tkiva pupčanika (UC-MSC, Umbilical cord-mesenchymal stem cells). U okviru razjašnjavanja efekata i mehanizama delovanja IL-17 na diferencijaciju mezenhimskih ćelija, primenjena je multipotentna mišja C2C12 ćelijska linija. Uticaj IL-17 na diferencijaciju analiziran je na osnovu ekspresije gena i proteina specifičnih za odreñeni tip diferencijacije: teškog lanca miozina (MyHC, Myosin heavy chain) i miogenina za miogenu, a alkalne fosfataze (ALP, Alkaline phosphatase), Runx2/Cbfa1 (Runt-related transcription factor 2/Core-binding factor subunit alpha-1) transkripcionog faktora i ciklooksigenaze 2 (Cox-2, Cyclooxygenase 2) za osteogenu diferencijaciju. Pored toga, utvrñivano je učešće mitogenom aktiviranih protein kinaza (MAPK) i morfogenetskih proteina kosti (BMP, Bone morphogenic proteins) u IL-17-usmerenoj diferencijaciji C2C12 ćelija. Rezultati su pokazali da IL-17 inhibira miogenu i stimuliše osteogenu diferencijaciju C2C12 ćelija, s obzirom na to da je IL-17-zavisna inhibicija miogeneze povezana sa redukcijom ekspresije iRNK za miogenin, redukcijom ekspresije MyHC i izostankom formiranja miotuba, dok je IL-17-zavisna indukcija osteogeneze povezana sa indukcijom ekspresije iRNK za Runx2/Cbfa1, indukcijom ekspresije Cox-2 i povišenom aktivnošću ALP. Rezultati su takoñe pokazali da IL-17 ostvaruje ove efekte putem aktivacije ERK1,2 MAPK signalnog puta, nezavisno od BMP-Smad signalnog puta. U drugom delu ove studije ispitivan je efekat IL-17 na funkcije endotelskih ćelija na modelu humane endotelske ćelijske linije, EA.hy 926, praćenjem njihove proliferacije, migracije i tubulogeneze u uslovima normoksije i hipoksije. Analizirana je i ekspresija gena za endotelsku azot monoksid sintazu (eNOS, Endothelial nitric oxide synthase) i Cox-2, kao i njihovih proteinskih produkata, budući da ovi molekuli imaju važnu ulogu u procesu angiogeneze. Dobijeni rezultati su potvrdili da IL-17 stimuliše ključne funkcije uključene u proces angiogeneze EA.hy 926 ćelija, poput ćelijske migracije i tubulogneze, kao i ekspresiju eNOS i Cox-2 u ovim ćelijama. Pro-angiogeni efekti IL-17 su pokazani u uslovima normoksije (20% O2). Uslovi hipoksije (3% O2) pokazali su toksično dejstvo na ovu ćelijsku liniju, dok je IL-17 u ovakvim uslovima umanjio broj apoptotičnih ćelija. U okviru trećeg dela ove disertacije MSC su izolovane iz vezivnog tkiva pupčanika, tzv. Vartonove sluzi, umnožene i okarakterisane prema važećim preporukama i kriterijumima Meñunarodnog društva za ćelijsku terapiju. Zatim je ispitan i odreñen optimalni protokol za njihovu efikasnu diferencijaciju u endotelske ćelije, u cilju uspostavljanja novog ćelijskog modela za buduća istraživanja. Princip diferenciranja UC-MSC u endotelske ćelije zasnivao se na inhibiciji signalizacije faktora transformacije rasta (TGF-β, Transforming growth factor beta), i to njegovog receptora, aktivinu-nalik kinaze 5 (ALK5, Activin-like kinase). Na osnovu dobijenih rezultata, zaključeno je da se UC-MSC odlikuju visokom sposobnošću samoobnove i visokim kapacitetom za diferencijaciju kao i da se mogu diferencirati u endotelske ćelije putem inhibicije ALK5 receptora Interleukin (IL) 17 cytokine family is considered the least explored cytokine family with an important role in inflammation. Due to the ubiquitous expression of its receptor, IL-17 has been implicated in interactions between the immune system and somatic tissues. In this context, recent findings have shown that IL-17 acts as a fine regulator of mesenchymal stem cell (MSC) differentiation. Having in mind that behaviour of MSC depends on the surrounding microenvironment, it is important to analyze the interactions between MSC and IL-17 involved in the maintenance of their multipotency, mobilization and directed differentiation. In addition to mesenchymal cells, IL-17 exerts its roles by acting on endothelial cells as well. Even though IL-17’s effects on endothelial cells have not been fully discovered yet, it is well known that IL- 17, in the presence of other angiogenic factors, has the ability to stimulate endothelial cells to undergo angiogenesis. Furthermore, it is well known that cellular functions, as well as cytokine effects can be significantly modulated by the percentage of oxygen present in their microenvironment. However, effects of IL-17 on endothelial cells in the context of different O2 concentrations have not been explored yet. Also, it is still unknown whether IL-17 can affect endothelial differentiation of MSC, but to address this issue, it is necessary to create a valid model of endothelial differentiation of MSC. The objective of this study was to investigate the effects of IL-17 on different functions of mesenchymal and endothelial cells in specific microenvironmental conditions. The influence of IL-17 on proliferation, migration, angiogenesis and differentiation was analyzed, as well as the molecular mechanisms involved. The activation of various signaling molecules and the expression of genes and proteins involved in specific functions were examined. Yet another objective was to establish an appropriate model for the mesenchymal-endothelial transdifferentiation. For this task primary MSC from umbilical cord tissue (UC-MSC) were isolated and characterized with emphases on their endothelial differentiation. In order to elucidate the effects and mechanisms involved in IL-17 acting on mesenchymal cell differentiation, a multipotent mouse C2C12 cell line was used. The influence of IL-17 on cell differentiation was analyzed based on the expression of genes and proteins specific for the certain type of differentiation: Myosin heavy chain (MyHC) and Myogenin for myogenic, and Alkaline phosphatase (ALP), Runt-related transcription factor 2/Core-binding factor subunit alpha-1 (Runx2/Cbfa1) and Cyclooxygenase-2 (Cox-2) for osteogenic differentiation. Additionaly, the involvement of Mitogen-activated protein kinases (MAPK) and Bone morphogenetic proteins (BMP) in IL-17-directed differentiation of C2C12 cells was investigated. Results obtained demonstrated that IL-17 inhibits myogenic and stimulates osteogenic differentiation of C2C12 cells, by down-regulating the Myogenin mRNA expression, MyHC expression and myotube formation, while up-regulating the Runx2/Cbfa1 mRNK expression, Cox- 2 expression and ALP activity. IL-17 exerted these effects by activating ERK1,2 MAPK signaling pathway, which in turn regulated the expression of relevant genes and proteins to inhibit myogenic differentiation and induce osteogenic differentiation. It was also shown that the induction of osteogenic differentiation by IL-17 is independent of the BMP-Smad signaling pathway. In the second part of this study the effect of IL-17 on endothelial cell functions was investigated using human endothelial cell line EA.hy 926 as a model. The changes in cells’ proliferation, migration and tubulogenesis were analyzed, along with the expression of genes for endothelial Nitric oxide synthase (eNOS) and Cox-2, and their corresponding protein products, since these molecules have important roles in angiogenesis. The influence of the environmental stimuli (normoxia vs. hypoxia) was also investigated. Results obtained demonstrated that IL-17 stimulates crutial events involved in angiogenesis of EA.hy 926 cells, such as cell migration and tubulogenesis, along with the expression of eNOS and Cox-2. However, the effects of IL-17 were dependent on the O2 concentration, since pro-angiogenic effects of IL-17 were noticed in the presence of 20% O2, while 3% O2 exerted toxic effect on this cell line, and IL-17 in these conditions decreased the number of apoptotic cells. In the final task, MSC were isolated from the umbilical cord Wharton’s jelly, expanded in culture and characterized according to the recomendations from the International Society for Cell Therapy. Following this, an optimal protocol for the endothelial diffrentiation of UC-MSC was established. The endothelial-directed differentiation was based on the inhibition of the Transforming growth factor beta (TGF-β) signaling, specifficaly its receptor activin-like kinase 5 (ALK5). Based on the results gained, it was concluded that UC-MSC have a high ability to selfrenew and high diferentiation capacity, as well as that these cells can be differentiated into endothelial cells by inhibiting ALK5 receptor Univerzitet u Beogradu Biološki fakultet Bugarski, Diana Korać, Aleksandra Santibañez, Juan 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=64 https://fedorabg.bg.ac.rs/fedora/get/o:3419/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024511922 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:68 2013-02-11T00:00:00Z 1

Uloga hormona jajnika u involuciji timusa pacova Role of ovarian hormones in thymic involution in rats : doctoral dissertation Perišić, Milica M., 1978- involucija timusa; hormoni jajnika; timusne epitelne ćelije; timopoeza; IL-6; IL-7; noradrenalin; adrenergički receptori; sveži timusni emigranti; regulatorne T ćelije thymic involution; ovarian hormones; thymic epithelial cells; thymopoiesis; IL-6; IL-7; noradrenaline; adrenergic receptors; recent thymic emigrants; regulatory T-cells Datum odbrane: 28.9.2012. Timus je primarni limfoidni organ koji obezbeđuje mikrosredinu neophodnu za diferencijaciju/sazrevanje T-limfocita. Tokom ontogeneze, ovaj organ trpi značajne strukturne i funkcionalne promene koje se zbirno označavaju kao involucija timusa, i manifestuju se kao smanjena efikasnosti timopoeze i posledično, smanjen izlazak novoformiranih T-limfocita na periferiju. Involucija timusa je kod glodara najizraženija u periodu sticanja polne zrelosti. Veliki broj literaturnih podataka ukazuje na to da hormoni hipotalamo-hipofizo-gonadne (H-H-G) osovine, pre svega hormoni gonada, utiču na razvoj i involuciju timusa. Međutim, uprkos brojnim istraživanjima u proteklim decenijama, uloga hormona jajnika u inicijaciji i održavanju/progresiji involucije timusa nije do kraja rasvetljena. Cilj ove doktorske disertacije je bio da se ispita uloga hormona jajnika u inicijaciji i održavanju/progresiji involucije timusa. U tom cilju ispitivan je uticaj jednokratnog davanja testosterona u kritičnom neonatalnom uzrastu, koji dovodi do odlaganja sazrevanja H-H-G osovine i promena u obrascu sekrecije hormona jajnika kod adultnih životinja (neonatalna androgenizacija) i uklanjanja jajnika ženkama pacova u uzrastu od 10 meseci, kada su involutivne promene timusa jasno izražene, na građu timusa i timopoezu u ranom adultnom uzrastu; odnosno u uzrastu od 11 meseci. Posebno je ispitivan, mogući, indirektan uticaj promena u sekreciji hormona jajnika na aktivnost timusnog kateholaminergičkog regulatornog sistema. Neonatalna androgenizacija, delujući na različite stadijume diferencijacije/sazrevanja T-ćelija, od ulaska/diferencijacije progenitorskih ćelija do linijskog usmeravanja timocita, povećala je efikasnost timopoeze (na osnovu većeg broja svežih timusnih emigranata u perifernoj krvi i slezini), uključujući, najverovatnije, i povećano stvaranje ćelija regulatornog fenotipa (CD4+CD25+FoxP3+ i CD161+TCRαβ+ ćelije). Pored toga, kod ovih životinja je uočeno favorizovano stvaranje ćelija CD4-CD8+TCRαβ++ fenotipa (fenotipska defeminizacija/maskulinizacija procesa timopoeze). Uprkos povećanoj efikasnosti timopoeze, nepromenjena relativna zastupljenost timusnih epitelnih ćelija (TEC) kao i nivo iRNK za IL-6, a smanjen nivo iRNK za IL-7 u tkivu timusa, ukazuju, da je kod neonatalno androgenizovanih životinja, u uzrastu od 3 meseca, najverovatnije, došlo do pokretanja mehanizama negativne povratne sprege, koji ograničavaju ekspanziju TEC i timopoezu. Ovarijektomija u uzrastu od 10 meseci, nakon 30. dana, imala je za posledicu povećanje relativne zastupljenosti TEC i efikasnosti timopoeze (uključujući i povećano stvaranje ćelija regulatornog fenotipa), što se manifestovalo povećanim brojem svežih timusnih emigranata CD4+ i CD8+ fenotipa u perifernoj krvi i slezini. Međutim, uprkos regeneraciji epitelne komponente timusa i povećanoj efikasnosti timopoeze, smanjen nivo iRNK za IL-6 i IL-7 u tkivu timusa ovarijektomisani životinja sugeriše da je kod ovih životinja došlo do aktivacije intratimusnih mehanizama negativne povratne sprege koji ograničava ekspanziju TEC koje sintetišu IL-6 i efikasnost timopoeze. U zaključku, nalazi dobijeni u ovoj disertaciji ukazuju da neonatalna androgenizacija menja kinetiku postnatalnog razvoja timusa i polno specifičan obrazac diferencijacije/sazrevanja timocita i odlaže, ali vrlo verovatno ne sprečava involuciju timusa, dok uklanjanje hormona jajnika u uzrastu kada su involutivne promene timusa uznapredovale dovodi do delimične reverzije ovih promena i efikasnije timopoeze, koji su, najverovatnije, vremenski ograničenog trajanja. Pored toga, pokazano je da se uticaj hormona jajnika na ove procese odvija i indirektno, menjanjem efikasnosti modulatornog delovanja noradrenalina na timopoezu. The thymus is a primary lymphoid organ that provides the microenvironment necessary for the differentiation/maturation of T-lymphocytes. During ontogeny, thymus undergoes significant structural and functional changes leading to reduced efficiency of thymopoiesis and, consequently, reduced output of newly generated Tlymphocytes. These changes are collectively referred to as thymic involution. The most profound thymic changes in rodents, occur around puberty. There is an accumulating body of evidence indicating that hormones of the hypothalamic-pituitary-gonadal (H-PG) axis, particularly gonadal hormones, influence thymic development and involution. However, despite extensive research in the past decades, the role of ovarian hormones in the initiation and maintenance/progression of thymic involution is not fully understood. Bearing all aforementioned in mind, this dissertation was aimed to elucidate the role of ovarian hormones in initiation and maintenance/progression of thymic involution. To this end the effects of single injection of testosterone in critical postnatal period, which postpones H-P-G axis maturation and affects the gender-specific pattern of gonadal hormone secretion in adult animals (neonatal androgenization), and ovarian hormone removal in rats with advanced thymic involutive changes (10-month-old), on thymic structure and function, were examined in 3-month-old and 11-month-old female rats, respectively. In addition, the putative indirect, catecholamine-mediated effects of the neonatal androgenization and ovariectomy on thymopoiesis were explored. Neonatal androgenization, affecting distinct stages of thymocyte differentiation/maturation (from progenitor cell entry and differentiation to thymocyte lineage commitment), increased the efficiency of thymopoiesis and consequently thymic output (as evidenced by the increased number of recent thymic emigrants in peripheral blood and spleen), including, most likely, increased output of the cells with regulatory phenotype (CD4+CD25+FoxP3+ and CD161+TCRαβ+ cells). In addition, neonatal treatment with testosterone skewed thymocyte lineage commitment towards CD4-CD8+TCRαβ++ cells (phenotypic defeminization/masculinization of thymopoiesis). Despite the increased efficiency of thymopoiesis, unaltered relative abundance of thymic epithelial cells (TEC) and the thymic level of IL-6 mRNA, and reduced thymic level of IL-7 mRNA, indicated, most likely, activation of intrathymic negative feedback mechanisms limiting TEC proliferation and thymopoiesis in 3- month-old neonatally androgenized rats. Ovariectomy at the age of 10 months led to the expansion of TECs and greater efficiency of thymopoiesis (including generation of cells with regulatory phenotype), increasing the number of both CD4+ and CD8+ recent thymic emigrants in peripheral blood and spleen of 11-month-old rats, compared with age-matched controls. However, despite the regeneration of the thymic epithelial component and increased efficiency of thymopoiesis, reduced thymic levels of mRNA for IL-6 and IL-7 in ovariectomized rats indicated activation of intrathymic negative feedback mechanisms limiting the expansion of IL-6-synthesizing TECs and thymopoietic efficiency in these animals. In conclusion, the data obtained in this dissertation indicate that neonatal androgenization alters the kinetics of postnatal thymic development and sex-specific pattern of thymocyte differentiation/maturation and postpones thymic involution, but, most likely, does not prevent it completely. The removal of ovarian hormones in female rats with advanced thymic involutive changes leads to partial reversion of these changes, and an increase in thymopoietic efficiency of, most likely, limited duration. In addition, these data indicate that ovarian hormones might affect thymic development/involution not only directly, but also indirectly by diminishing the efficiency of noradrenaline-mediated modulation of thymopoiesis. Univerzitet u Beogradu Biološki fakultet Leposavić, Gordana Leposavić, Gordana, Božić, Biljana Božić, Biljana Vučević, Dragana 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=68 https://fedorabg.bg.ac.rs/fedora/get/o:3435/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41905423 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:69 2013-09-19T00:00:00Z 1

Povezanost polimorfizama VDR, CYP27B1 i CYP24A1 gena sa etiološkim faktorima i ishodom bolesti kod pacijenata sa oralnim skvamocelularnim karcinomom Association of polymorphisms in VDR, CYP27B1 and CYP24A1 genes with etiological factors and disease outcomes in patients with oral squamous cell carcinoma : doctoral dissertation Zeljić, Katarina 1984- Oralni skvamocelularni karcinom, polimorfizmi nukleotidne sekvence, VDR gen, CYP27B1 gen, CYP24A1 gen Oral squamocellular carcinoma, single nucleotide polymorphism, VDR gene, CYP27B1 gene, CYP24A1 gene Datum odbrane: 5.11.2012. Oralni skvamocelularni karcinomi (Oral Squamous Cell Carcinoma- OSCC) se karakterišu visokom stopom mortaliteta, lošom prognozom i porastom incidence među osobama mlađe populacije. I pored uloženih napora na polju prevencije, petogodišnje preživljavanje je ostalo nepromenjeno poslednjih nekoliko decenija, što nameće potrebu za nove, molekularne vidove karakterizacije oralnog karcinoma. Poznati faktori rizika za nastanak oralnog karcinoma su: pušenje i žvakanje duvana, konzumiranja alkohola, loša oralna higijena i infekcije visokorizičnim tipovima humanog papiloma virusa. Činjenica da samo izvesni procenat osoba izloženih navedenim faktorima rizika zaista i razvije OSCC, ukazuje na značaj genetičke osnove u procesu oralne kancerogeneze. Mnogobrojnim studijama je pokazano da vitamin D ima antikancerogeni efekat, koji se ogleda u zaustavljanju ćelijskog ciklusa, inicijaciji ćelijske diferencijacije, indukciji apoptoze, sprečavanju invazije malignih ćelija i antiangiogenetskom dejstvu. Vitamin D ispoljava svoju fiziološki aktivnu ulogu nakon vezivanja za receptor za vitamin D (engl. Vitamin D Receptor- VDR) koji je kodiran VDR genom. U VDR genu je identifikovan veliki broj polimorfizama nukleotidne sekvence (engl. Single Nucleotide Polymorphisms- SNP), od kojih samo mali broj ima funkcionalni efekat. U metabolizam vitamina D su uključeni članovi velike familije proteina citohroma P450 i to: 1α-hidroksilaza uključena u proces anabolizma (kodirana CYP27B1 genom), odnosno 24-hidroksilaza koja ima ulogu u katabolizmu (kodirana CYP24A1 genom). Obzirom na značaj proučavanja SNP-ova u genetičkim studijama asocijacije, postavlja se pitanje da li postojanje izvesnih genetičkih varijanti u genima uključenim u funkcionisanje i metabolizam vitamina D može biti asocirano sa rizikom nastanka oralnog karcinoma, kliničko patološkim karakteristikama i preživljavanjem pacijenata... Oral Squamous Cell Carcinoma (OSCC) is characterized with a high mortality, low survival rate and rising incidences among members of younger age groups. Despite efforts in prevention, the survival rate remains unchanged for the last few decades, which indicates the need for oral cancer molecular characterization. The well-known risk factors are tobacco smoking and chewing, alcohol consumption, poor oral hygiene and infection with high risk human papilloma virus types. The fact that only a small percentage of people exposed to the risk factors really develops OSCC indicates the importance of genetic background in the process of oral cancerogenesis. Numerous studies have demonstrated the anticancerogen effects of vitamin D, which is reflected in cell cycle arrest, induction of cell differentiation, apoptosis induction, inhibition of malignant cell invasion and antiangiogenic effect. Vitamin D exerts it’s physiological function after binding to the Vitamin D Receptor (VDR), which is encoded by the VDR gene. A great number of Single Nucleotide Polymorphisms (SNPs) have been identified in the VDR gene, among which a small number have functional effects. Members of the huge protein cytochrome P450 family are involved in vitamin D metabolism: 1α-hydroxylase is involved in anabolism (encoded by the CYP27B1 gene) and 24-hydroxylase is involved in catabolism (encoded by the CYP24A1 gene). Since SNPs investigation is of great importance in the genetic association studies, it is interesting to consider whether genetic variants in genes, involved in vitamin D functioning and metabolism, could be associated with oral cancer risk, clinicopathological characteristics and patient survival... Univerzitet u Beogradu Biološki fakultet Stamenković-Radak, Marina Magić, Zvonko Milašin, Jelena 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=69 https://fedorabg.bg.ac.rs/fedora/get/o:3437/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024527538 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:70 2013-09-19T00:00:00Z 1

Molekularna osnova hronične limfocitne leukemije : korelacija između mutacionog statusa teških lanaca imunoglobulina i ekspresije apoptotskih gena Molecular basis of chronic lymphocytic leukemia: correlation between the immunoglobulin heavy chain mutational status and the expression of apoptotic genes Karan-Đurašević, Teodora, 1973- Hronična limfocitna leukemija, IGHV mutacioni status, apoptoza, Bcl2, Bax, Bcl2L12 Chronic lymphocytic leukemia, IGHV mutational status, apoptosis, Bcl2, Bax, Bcl2L12 Datum odbrane: 6.11.2012. Hronična limfocitna leukemija (HLL), najčešći tip leukemije u Evropi i Severnoj Americi, se manifestuje kao klonska ekspanzija zrelih CD5+ CD19+ CD23+ sIgM+/- B limfocita i karakteriše se izuzetno heterogenim kliničkim tokom. Leukemični, kao i normalni B limfociti, na svojoj površini eksprimiraju imunoglobulinski antigenski receptor. Struktura varijabilnog regiona njegovog teškog lanca (IGH) je determinisana specifičnim rearanžmanima između IGHV, IGHD i IGHJ gena, koji se odvijaju tokom diferencijacije B ćelija. Nakon susreta sa antigenom, B limfociti ulaze u proces afinitetnog sazrevanja u germinalnim centrima sekundarnih limfnih folikula, tokom koga dolazi do akumulacije somatskih hipermutacija u IGHV-IGHD-IGHJ rearanžmanima. Pokazano je da je mutacioni status rearanžiranih gena za varijabilni region teških lanaca imunoglobulina (IGHV) najpouzdaniji molekularni marker u HLL, koji definiše dva podtipa bolesti: M-HLL i N-HLL. Pacijenti sa malim procentom ili bez IGHV mutacija (N-HLL) obično imaju mnogo agresivniji tok bolesti i lošiju prognozu od pacijenata sa mutiranim IGH rearanžmanima (M-HLL). Razlike u IGHV genskom repertoaru između M-HLL i N-HLL klonova, populacione varijacije u učestalosti određenih IGHV gena u HLL rearanžmanima kao i ekspresija visoko homologih, ˝stereotipnih˝ rearanžmana, ukazuju na ulogu antigenske stimulacije u patogenezi HLL.HLL se smatra tipičnim primerom maligniteta uzrokovanog poremećajima u procesu apoptoze. U HLL su detektovane genetičke promene i aberantna ekspresija brojnih proteina regulatora apoptoze, koji su uključeni kako u spoljašnji tako i u unutrašnji put aktivacije ovog procesa. Smatra se da je smanjeni apoptotski potencijal HLL klonova uzrokovan, između ostalog, i poremećajima u ekspresiji proteina Bcl2 familije. U ovom radu je analiziran IGHV mutacioni status i genski repertoar IGHV-IGHD-IGHJ rearanžmana kod pacijenata obolelih od HLL. Pored toga, analizirana je ekspresija gena Bcl2 familije, kao osnovnih regulatora unutrašnjeg puta aktivacije apoptoze, u cilju utvrđivanja njihove uloge u apoptotskoj rezistenciji HLL B limfocita. qRT-PCR metodom je merena ekspresija Bcl2, Bax i Bcl2L12 gena, i ispitivana asocijacija nivoa njihove ekspresije sa odabranim kliničkim i molekularnim prognostičkim faktorima (IGHV mutacionim statusom, ekspresijom CD38 i lipoprotein lipaze). Bcl2L12 je novi član Bcl2 familije apoptotskih proteina čija pro- ili anti-apoptotska funkcija još uvek nije razjašnjena. Pored analize ekspresije Bcl2L12 gena u HLL, jedan od ciljeva ovog rada je bilo i definisanje promotorskog regiona i mesta starta transkripcije Bcl2L12, što je neophodno za proučavanje mehanizama njegove transkripcione regulacije. Određivanjem IGHV mutacionog statusa je pokazano da 55.3% analiziranih pacijenata pripada M-HLL, a 44.7% N-HLL podtipu, kao i da u N-HLL preovlađuju pacijenti sa progresivnim oblikom bolesti. U analiziranim rearanžmanima su sa najvećom frekvencom bili zastupljeni geni IGHV3 familije (55.7%), a zatim IGHV1 (27.3%), IGHV4 (12.5%), IGHV5 (2.3%), IGHV2 (1.1%) i IGHV6 (1.1%) geni. Pokazano je prisustvo tzv. ˝stereotipnih˝ rearanžmana kod 15.3% pacijenata, predominantno u N-HLL podtipu. Na osnovu određenih frekvenci IGHV, IGHD i IGHJ gena i genskih familija je zaključeno da je IGH genski repertoar leukemičnih klonova kod pacijenata iz Srbije veoma sličan repertoaru detektovanom kod pacijenata iz zemalja mediteranskog područja, sa izuzetkom gena IGHV4 familije koji su kod pacijenata u ovoj studiji zastupljeni sa manjom učestalošću.Analizom ekspresije Bcl2, Bax i Bcl2L12 su detektovani znatno viši nivoi ekspresije sva tri gena kod HLL pacijenata u odnosu na zdrave kontrole, pri čemu je povećanje ekspresije bilo najizraženije u slučaju Bcl2 gena. Povišena ekspresija Bcl2 je pokazala asocijaciju sa nepovoljnim prognostičkim parametrima: progresivnim tipom bolesti, visokim nivoom serumskog β2-mikroglobulina i povišenim nivoom ekspresije gena za lipoprotein lipazu (LPL). Ekspresija Bax je pokazala korelaciju samo sa ekspresijom LPL, dok je ekspresija Bcl2L12 bila relativno homogena među HLL pacijentima i, kao takva, nije ispoljila značajnu asocijaciju sa većinom kliničkih i molekularnih prognostičkih faktora. Ekspresija Bcl2, Bax i Bcl2L12 je bila viša u grupi N-HLL pacijenata u odnosu na M-HLL pacijente, ali ova razlika nije dostigla statističku značajnost.Kloniranjem fragmenata 5' kraja Bcl2L12 gena i funkcionalnom analizom reporterskih konstrukata, detektovan je region koji ispoljava jaku promotorsku aktivnost. Ovaj region se prostire od 338 nukleotida uzvodno, do 148 nizvodno od početka kodirajućeg dela egzona 1, a esejom usporene elektroforetske pokretljivosti (˝EMSA˝) je pokazano da se za njega vezuju Sp1 i GATA-1 transkripcioni faktori. Metodom elongacije reverznog prajmera (˝primer extension˝) je određen položaj starta transkripcije Bcl2L12 gena, 33 nukleotida uzvodno od translacionog start kodona Chronic lymphocytic leukemia (CLL), the most common type of leukemia in Western countries, manifests as clonal expansion of mature CD5+ CD19+ CD23+ sIgMlow B lymphocytes and it is characterized by an extremely heterogeneous clinical course. Leukemic, as well as normal B lymphocytes, express immunoglobulin antigenic receptor at their surface. The structure of its heavy chain (IGH) variable region is being formed during B-cell differentiation, through rearrangements between IGHV, IGHD and IGHJ genes. After antigen encouner, B lymphocytes undergo the process of affinity maturation in germinal centers of secondary lymphoid follicles, durring which IGHV-IGHD-IGHJ rearrangements accumulate somatic hypermutations. It has been shown that the mutational status of rearranged immunoglobulin heavy variable genes (IGHV) represents the most reliable molecular marker in CLL, which defines two CLL subsets: M-CLL and U-CLL. The patients without or with a small percentage of IGHV mutations (UCLL) usually have more agressive disease and inferior prognosis in comparison to patients expressing mutated IGH rearrangements (M-CLL). Biased IGHV gene repertoire between MCLL and U-CLL clones, population differences in IGHV gene usage, as well as the expression of highly homologous, ˝stereotyped˝ rearrangements, strongly imply the role of antigenic stimulation in pathogenesis of CLL.CLL typifies the malignancy caused by defective apoptosis. Genetic alterations and aberrant expression of numerous proteins involved in extrinsic and intrinsic pathways of apoptosis regulation have been described in CLL. Reduced apoptotic capacity of CLL clones is, in part, caused by disturbances in the expression of Bcl2 family proteins. In this study, we analized IGHV mutational status and gene repertoire of IGHV-IGHD-IGHJ rearrangements in CLL patients. Furthermore, the expression of Bcl2 family genes, the key regulators of intrinsic apoptotic pathway, has been studied, in order to elucidate their role in resistance of CLL B lymphocytes to apoptosis. The expression levels of Bcl2, Bax and Bcl2L12 genes were measured by qRT-PCR, and association of their expression with clinical and molecular prognostic factors (IGHV mutational status, expression of CD38 and lipoprotein lipase) was analized. Bcl2L12 is a novel member of Bcl2 family of apoptotic proteins, whose pro- or anti-apoptotic function has not been elucidated yet. Besides the expression analysis of Bcl2L12 gene in CLL, one of the aims of this dissertation was defining the promoter region and transcription start site of Bcl2L12, which is essential for the study of mechanisms involved in its transcriptional regulation. The analysis of IGHV mutational status showed that 55.3% of patients enrolled in this study belonged to M-CLL, and 44.7% to U-CLL subset, and that in U-CLL predominated patients with the progressive form of the disease. The most frequently expressed genes were those belonging to IGHV3 family (55.7%), followed by IGHV1 (27.3%), IGHV4 (12.5%), IGHV5 (2.3%), IGHV2 (1.1%) i IGHV6 (1.1%) genes. The presence of ˝stereotyped˝ rearrangements was detected in 15.3% of patients, predominantly in U-CLL subset. Based on the determined frequencies of IGHV, IGHD and IGHJ genes and gene families, we concluded that the IGH gene repertoire of leukemic clones of Serbian CLL patients closely resembles the repertoire observed in patients from Mediterranean countries, with the exception of IGHV4 family, which was underrepresented in our cohort. The expression analysis of Bcl2, Bax and Bcl2L12 showed that those three genes were overexpressed in CLL patients compared to healthy controls, and that elevation of expression level was the most prominent in the case of Bcl2 gene. High expression levels of Bcl2 were associated with unfavorable prognostic parameters: progressive form of the disease, elevated β2- microglobulin and high expression of lipoprotein lipase gene (LPL). The expression of Bax was correlated only with the expression of LPL, while the expression of Bcl2L12 turned out to be relatively homogenous among CLL patients and, as such, failed to show association with the majority of clinical and molecular prognostic factors. Expression levels of Bcl2, Bax and Bcl2L12 were higher in U-CLL in comparison to M-CLL group of patients, but this difference did not reach statistical significance.Cloning of fragments corresponding to 5' end of Bcl2L12 gene and functional analysis of reporter constructs, led to identification of a region which exerts high promoter activity. This region extends from 338 nucleotides upstream, to 148 nucleotides downstream relative to the beginning of exon 1 coding sequence, and electromobility shift assay (˝EMSA˝) showed that it binds Sp1 and GATA-1 transcription factors. Transcription start site of Bcl2L12 gene was determined by primer extension assay, which showed that it is located 33 nucleotides upstream of translation start codon. Univerzitet u Beogradu Biološki fakultet Pavlović, Sonja Pavlović, Sonja Savić-Pavićević, Dušanka Savić-Pavićević, Dušanka Tošić, Nataša 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=70 https://fedorabg.bg.ac.rs/fedora/get/o:3444/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41903375 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:71 2013-02-13T00:00:00Z 1

Ekološka analiza zajednice makrozoobentosa reke Nišave Ecological analysis of macrozoobenthos communities in the Nišava River : doctoral dissertation Savić, Ana V. 1978- faktori sredine, faunistička raznovrsnost, trofičke gilde, makroinvertebrate, reka Nišava, struktura zajednica, zagađenost vode environmental factors, faunistic diversity, trophic guilds, macroinvertebrates, Nišava River, community structure, water pollution Datum odbrane: 6.10.2012. Doktorska disertacija obuhvata ekološku analizu zajednica makrozoobentosa reke Nišave i njihovu zavisnost od biotičkih i abiotičkih faktora. Istraživanja su obavljena mesečnom dinamikom na dvanaest lokaliteta od maja 2006. do aprila 2007. godine. U disertaciji se diskutuje zavisnost koncentracije hlorofila a i mase perifitona od abiotičkih faktora. Sa druge strane, razmatran je pritisak (na osnovu brojnosti) filtratornih vrsta zajednice makroinvertebrata na količinu fitoplanktona (izraženu preko hlorofila a) i pritisak grebača na masu perifitona. Dobijen je predikcioni model za izračunavanje koncentracije hlorofila a korišćenjem multiple linearne regresije. Model ima značajnu predikcionu moć (sig=0,003). Na osnovu Pirsonovog koeficijenta korelacije konstatovano je da postoji značajna povezanost koncentracije hlorofila a sa mutnoćom (p=0,000), sa ukupnim fosforom (p=0,029) i sa kombinovanom (zbirnom) koncentracijom ukupnog azota i fosfora (p=0,036). Nije utvrđena značajna povezanost sa brojnošću filtratornih organizama, što govori da njihov pritisak nije dovoljno jak da bi limitirao količinu fitoplanktona. Taksonomskom analizom makroinvertebrata reke Nišave utvrđeno je prisustvo 132 vrste iz 4 različita filuma. Filum Platyhelminthes je predstavljen sa 3 vrste iz 2 familije. Filum Annelida obuhvata 23 vrste iz 6 familija. Najveći broj vrsta ovog filuma pripada potklasi Oligochaeta (16 vrsta). Filum Mollusca obuhvata 13 vrsta iz 5 familija, od kojih 11 pripada klasi Gastropoda, a 2 klasi Bivalvia. Najveći broj vrsta faune makroinvertebrata pripada filumu Arthropoda (92 vrste iz 33 familije), od kojih 3 pripadaju subfilumu Crustacea, a sve ostale podfilumu Hexapoda, odnosno klasi Insecta. Rezultati taksonomske analize pojedinačnih grupa u okviru zajednice makroinvertebrata pokazuju da najveći broj vrsta pripada grupi Ephemeroptera (28 vrsta), zatim slede Diptera (26 vrsta) i Trichoptera (20 vrsta). Ostale grupe su zastupljene sa manjim brojem vrsta. Diskutovana je sezonska i longitudinalna dinamika grupa makroinvertebrata i njihova uslovljenost faktorima sredine. Razmatrani su indeksi diverziteta i adekvatnost njihovog korišćenja kao pokazatelja zagađenosti ekosistema, posebno za svaku grupu... This doctoral dissertation comprises the ecological analysis of macrozoobenthos communities in the Nišava River and their dependence on biotic and abiotic factors. The studies followed the monthly dynamics at 12 sites, from May 2006 to April 2007. The dissertation is discussing the dependence of chlorophyll a concentration and periphyton mass on abiotic factors, as well as the pressure (based on abundance) of filtrating species in the macroinvertebrate community on the amount of phytoplankton (expressed as chlorophyll a) and pressure of scraper species on periphyton mass. The prediction model for calculating chlorophyll a concentration was derived from the multiple linear regression. This model has a significant prediction power (sig=0.003). The Pearson's correlation coefficient was used to determine the correlation of chlorophyll a concentration with water turbidity (p=0.000), total phosphorus (p=0.029) and combined (summative) concentration of total nitrogen and total phosphorus (p=0.036). No significant connection with the abundance of filtrating organisms was determined, which indicates that their pressure was not strong enough to limit the quantity of phytoplankton. The taxonomic analysis of macroinvertebrates in the Nišava River yielded the presence of 132 species from 4 different phyla. The phylum Platyhelminthes was represented with 3 species from 2 families. The phylum Annelida was represented with 23 species from 6 families. Most recorded species from this phylum belong to the subclass Oligochaeta (16 species). The phylum Mollusca was represented with 13 species from 5 families, of which 11 were from the class Gastropoda and 2 from the class Bivalvia. Most species of the macroinvertebrate fauna belong to the phylum Arthropoda (92 species from 33 families), of which 3 were from the subphylum Crustacea, while all others belong to the subphylum Hexapoda and class Insecta. The results of the taxonomic analysis of individual groups within the macroinvertebrate community have shown that most species belong to the group Ephemeroptera (28 species), followed by Diptera (26 species), and Trichoptera (20 species). Other groups were represented with a smaller number of species. The study also includes the discussion on seasonal and longitudinal dynamics of macroinvertebrate groups and the effect of environmental factors on their presence. The diversity indices and their suitability as indicators of ecosystem pollution were discussed for each group separately... Univerzitet u Beogradu Biološki fakultet Krpo-Ćetković, Jasmina, 1961- Krpo-Ćetković, Jasmina, 1961- Živić, Ivana, 1972- Živić, Ivana, 1972- Marković, Zoran, 1963- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=71 https://fedorabg.bg.ac.rs/fedora/get/o:3461/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024510386 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:72 2013-02-13T00:00:00Z 1

Alelopatski efekti transformisanih korenova Chenopodium murale L. in vitro Allelopathic effects of Chenopodium murale L. hairy roots in vitro : doctoral dissertation Dmitrović, Slavica S., 1975- Agrobacterium rhizogenes, alelopatija, antioksidativni enzimi, Chenopodium murale, fenolne kiseline, genetička transformacija, geni ćelijskog ciklusa, hairy roots, qPCR, rol geni Agrobacterium rhizogenes, allelopathy, antioxidant enzyme, Chenopodium murale L., phenolic acids, genetic transformation, cell cycle-related genes, hairy roots, qPCR, rol genes Datum odbrane: 2.10. 2012. Korenov sistem C. murale produkuje i luči hemijske materije koje imaju alelopatsku aktivnost. Proučavanje efekata na druge organizme, kao i izolovanje i karakterizacija metabolita koji su izlučeni iz korenova u zemljište je veoma kompleksan proces. Zbog toga je cilj ovog istraživanja bio uspostavljanje kulture transformisanih korenova C. murale in vitro, kao novog sistema pogodnog za izučavanje alelopatskog efekta. Transgeni korenovi su indukovani pomoću Agrobacterium rhizogenes A4M70GUS na eksplantatima korenova, kotiledona, listova i internodija klijanaca C. murale. Eksplantati korenova su imali najveću efikasnost transformacije (11,1%). Uspostavljeni su klonovi transformisanih korenova različite morfologije i potencijala rasta koji se gajenjem (subkultivisanjem) u tečnom MS medijumu održavaju više od dve godine. Potvrda transformacije ovih klonova je urađena pomoću PCR, RT–PCR i histohemijske GUS analize. Nije ustanovljena razlika u prisustvu rol gena među klonovima. Ispitivan je alelopatski efekat tečnih medijuma u kojima su rasli transformisani i netransformisani korenovi C. murale (fitotoksični medijum) na klijanje i rast klijanaca test biljaka arabidopsisa (Arabidopsis thaliana (L.) Heynh), pšenice (Triticum aestivum L.) i salate (Lactuca sativa L.). Kod sve tri test biljke ustanovljen je inhibitorni efekat na klijanje semena i rast klijanaca. Klonovi transformisanih klonova: R1 i R8, imali su najveći alelopatski potencijal. Kod test biljaka arabidopsisa i pšenice, koje su bile tretirane fitotoksičnim medijumima, praćena je ukupna aktivnost antioksidativnih enzima – katalaza, peroksidaza i superoksid dismutaza (spektrofotometrijski), kao i zastupljenost i aktivnost pojedinih izoformi navedenih enzima (elektroforetski). Aktivnost ovih enzima (izuzev katalaza kod arabidopsisa) bila je povećana kod klijanaca isklijavanih i gajenih na fitotoksičnim medijumima, što je u skladu sa aktiviranjem odbrambenih mehanizama u biljkama kada se one bile izlažu stresu (fitotoksinima, tj. alelohemikalijama). Fitotoksični medijumi različitih klonova transformisanih korenova dovodili su do različitog nivoa povećanja aktivnosti katalaza, peroksidaza i superoksid dismutaza kod različitih test biljaka... Root system produces and releases chemical compounds with allelopathic activity. Isolation and characterization of these metabolites, as well as investigation of their effects on other organisms, are very complicated processes. The aim of the present study was to initiate and establish Chenopodium murale L. transgenic hairy root in vitro culture system, as a new tool for allelopathic assays. Transgenic hairy roots were induced by Agrobacterium rhizogenes A4M70GUS from roots, cotyledons, leaves and internodes of C. murale seedlings. Roots were found to be the best target explants, providing transformation efficiency of up to 11.1%. Established 13 hairy root clones differed in their morphology and growth potential. The liquid culture system of characterized hairy root clones was maintained for over two years. Molecular characterization of these clones was carried out by PCR, RT-PCR and histochemical GUS analyses. No differences in rol gene presence were observed. We investigated allelopathic effect of wild-type and hairy root growth media (phytotoxic media) against germination and seedling development of Arabidopsis thaliana (L.) Heynh, wheat (Triticum aestivum L.) and lettuce (Lactuca sativa L.) test plants. The inhibitory potential varied depending on the test plant and hairy root clone. R1 and R8 clones had strong allelopathic effects. These results revealed that hairy roots as an independent system synthesize some bioactive substances with allelopathic activity and exude them into the growth medium. In test plants A. thaliana and wheat, after treatment with phytotoxic media, activity of different antioxidative enzymes (catalase, peroxidase and superoxide dismutase) were analyzed spectrophotometrically and electrophoretically. Activities of these antioxidative enzymes were higher in comparison to the control, except the catalase activity in A. thaliana, which was the same or lower. Phytotoxic media from different hairy root clones cause different changes in activities of catalases, peroxidases and superoxide dismutases in test plants... Univerzitet u Beogradu Biološki fakultet Ninković, Slavica Sabovljević, Aneta Mitić, Nevena. Simonović, Ana Maksimović, Vuk 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=72 https://fedorabg.bg.ac.rs/fedora/get/o:3463/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41901071 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:74 2013-02-20T00:00:00Z 1

Promena aktivnosti Na+/K+ pumpe i njen uticaj na spontanu bioelektričnu aktivnost neurona vinogradskog puža Helix pomatia L. pod dejstvom magnetnog polja Change in the activity of Na+/K+ pump and its effect on the spontaneous bioelectric activity of neuron of the garden snail Helix pomantia L. in the magnetic field : doctoral dissertation Nikolić, Ljiljana M. 1978- spontana bioelektrična aktivnost, statičko magnetno polje , Na+/K+ pumpa, intracelularna registracija, puž spontaneous bioelectric activity, static magnetic field, Na+/K+ pump ,intracellular registration, garden snail Datum odbrane: 18.10.2012. aktivnost neurona ima veliki značaj jer je magnetno polje umerene jačine prisutno u životnoj sredini. Jednako važno je i proučavanje mehanizama delovanja umereno jakog statičkog magnetnog polja na biofizičke osobine membrane neurona usled sve veće terapijske primene ovog polja, s tim što odgovarajuća jačina polja i dužina izlaganja polju tek treba da budu precizno određene. Uporednim eksperimentima primenom tehnike intracelularne registracije utvrđeno je da kratkotrajno izlaganje (15 min) umereno jakom statičkom magnetnom polju jačine 2,7 mT i 10 mT dovodi do promena bioelektrične aktivnosti spontano aktivnog Br neurona, dok promene nisu uočene kod nemog N1 neurona. Magnetno polje od 2,7 mT povećalo je amplitudu i skratilo trajanje akcionog potencijala, dok je magnetno polje od 10 mT hiperpolarisalo membranu, povećalo amplitudu, smanjilo frekvenciju i trajanje akcionog potencijala Br neurona. Veličine promena ispitivanih parametara zavisile su od jačine magnetnog polja i uočavane su i tokom perioda od 20 min nakon prestanka izlaganja Br neurona polju od 2,7 mT i 10 mT. Kombinovanim eksperimentima, biohemijskim analizama i 31P NMR spektroskopijom na okoloždrelnom ganglijskom kompleksu kao i tehnikom intracelularne registracije na Br neuronu vinogradskog puža, pronađeno je da kratkotrajno izlaganje (15 min) statičkom magnetnom polju jačine 10 mT povećava aktivnost Na+/K+ pumpe. Povećana aktivnost Na+/K+ pumpe dovodi do povećanja potrošnje ATP-a, kao i povećanja pHi posredstvom povećanja aktivnosti Na+/H+ izmenjivača, pH regulatornog sistema čija je aktivnost zavisna od gradijenta Na+ jona koji stvara i održava Na+/K+ pumpa. Rezultati elektrofizioloških eksperimenata na Br neuronu u saglasnosti su sa rezultatima dobijenim na okoloždrelnom ganglijskom kompleksu... It is important to investigate the effects of moderate intensity static magnetic field on the bioelectric activity of neurons, since this field is present in the environment. Equally important is to reveal the mechanism of action of moderate intensity static magnetic field on biophysical properties of neuronal membranes, as this field has been applied in disease treatment, whereby proper dosages of exposure still need to be determined. Comparative intracellular registration studies showed that short term exposure (15 min) to the moderate intensity static magnetic field of 2,7 mT and 10 mT strength changed bioelectric activity of the spontaneously active Br neuron, while bioelectric activity of silent N1 neuron remained unchanged. The 2,7 mT magnetic field increased amplitude and decreased duration of action potential, whereas the 10 mT magnetic field hyperpolarized membrane potential, increased amplitude, decreased firing frequency and duration of action potential of the Br neuron. The magnitude of change of measured bioelectric parameters depended on the strength of applied magnetic field, and was still observed during the period of 20 min after exposure of Br neuron to the 2,7 mT and 10 mT magnetic field. Combined experiments, using biochemical analysis and NMR spectroscopy on whole snail brains and intracellular registration on Br neuron, showed that short-term exposure (15 min) to the 10 mT magnetic field increased activity of Na+/K+ pump. Increased Na+/K+ pump activity in the snail brain caused an increase in ATP consumption and increase in the pHi which is mediated through an increase in the activity of Na+/H+ exchanger, a pH regulatory system governed by the gradient of Na+ ions created and maintained by Na+/K+ pump. Electrophysiology from Br neuron is in agreement with the results obtained on the whole snail brain... Univerzitet u Beogradu Biološki fakultet Živić, Miroslav Nedeljković, Miodrag. 1951- Kartelija, Gordana Todorović, Nataša Zakrzewska, Joanna 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=74 https://fedorabg.bg.ac.rs/fedora/get/o:3471/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024529330 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:75 2013-02-20T00:00:00Z 1

Uticaj elektromagnetnog polja (0,5 mT, 50 Hz) na motorno ponašanje, parametre oksidativnog stresa i morfološke karakteristike mozga nakon eksperimentalno izazvane moždane ishemije na modelu pustinjskog miša Influence of electromagnetic field (0,5mT, 50 Hz) on motor behaviour, oxidative stress parameters and morphological characteristicsof brain after global cerebral ischemia in mongolian gerbils : doctoral dissertation Rauš, Snežana, 1980- moždana ishemija, elektromagnetno polje, motorno ponašanje, oksidativni stres, morfologija cerebral ischemia, electromagnetic field, motor behaviour, oxidative stress, morphology Datum odbrane: 7.11.2012. današnje vreme, jedna od najčešćih bolesti koja pogaña celokupno društvo je moždani udar, koji može biti uzrokovan moždanom ishemijom. Osim što u velikom procentu dovodi do smrti, posledice moždanog udara su najčešće trajne i za njih ne postoji efikasna terapija. Još jedna karakteristika modernog doba je razvitak elektronske industrije i primena sve raznovrsnijih električnih ureñaja, a samim tim i povećanje stepena zagañenja “elektromagnetnim smogom”. Povećano prisustvo niskofrekventnih elektromagnetnih polja (EMP) je privuklo interesovanje velikog broja naučnika te su ispitivani njegovi efekti, izmeñu ostalog i na funkcionalne karakteristike centralnog nervnog sistema. Na osnovu poznatih činjenica o njegovom dejstvu možemo pretpostaviti da ovo polje utiče i na razvoj patofizioloških dogañaja i oporavak u uslovima moždane ishemije. Cilj naše studije je bio da ispitamo da li elektromagnetno polje (0,5 mT, 50 Hz, u trajanju od 7 dana) utiče na hipermotorno ponašanje pustinjskih miševa izazvano 10-min globalnom moždanom ishemijom i to 1., 2., 4. i 7. dana (neposredan efekat EMP), kao i 14. dana nakon reperfuzije (odloženi efekat EMP). Takoñe, na modelu moždane ishemije smo ispitali da li primenjeno EMP utiče na parametre oksidativnog stresa, koji su inače povišeni nakon moždane ishemije, u pojedinim regionima mozga 7. i 14. dana nakon reperfuzije. Praćen je i uticaj EMP na morfološke promene u najosetljivijim strukturama mozga (hipokampus, striatum i kora velikog mozga) izazvane ishemijom 7. i 14. dana... Nowadays, one of the most common diseases, which affect the whole society, is brain stroke, which can be caused by cerebral ischemia. Beside high mortality rate, consequences of brain stroke are often permanent without appropriate treatment. Another hallmark of modern society is development of electronic industry and usage of diverse electron devices, therefore increasing degree of pollution with “electromagnetic smog”. The increased presence of extremely low frequency magnetic fields (ELF-MF) has attracted the interest of many scientists to explore its effects, among others, on functional properties of central nervous system. Based on the known facts of its action, we can propose that this field affects development of pathophysiological events and recovery in conditions like cerebral ischemia. The purpose of this study was to determine whether ELF-MF (0.5 mT, 50 Hz, continuous exposue during 7 days) affects hypermotor activity of gerbils, induced by 10-min global cerebral ischemia on the 1st, 2nd, 4th and 7th day (immediate effect) as well as on the 14th day after reperfusion (delayed effect). Also, on this model we examined whether applied ELF-MF affect oxidative stress parameters, otherwise increased after cerebral ischemia, in some brain regions on the 7th and 14th reperfusion day. Also, we examined effect of ELF-MF on morphological changes in the most vulnerable structures of brain (hippocampus, striatum and forebrain cortex) induced by ischemia on the 7th and 14th reperfusion day, as well as performed quantification of this changes in neurons and glial cells. Animal behaviour was monitored for 60 min in the open field. It was shown that the 10-min global cerebral ischemia per se induced a significant... Univerzitet u Beogradu Biološki fakultet Janać, Branka Radenović, Lidija, 1966- Selaković, Vesna Prolić, Zlatko Manojlović-Stojanoski, Milica 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=75 https://fedorabg.bg.ac.rs/fedora/get/o:3473/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/41902351 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:76 2013-02-20T00:00:00Z 1

Hipofizno-ovarijalni sistem pacova od fetalnog do peripubertalnog perioda života nakon intrauterinog izlaganja deksametazonu Pituitary-ovarian axis of rats from fetal to peripubertal period of life after intrauterine exposure to dexamethasone : doctoral dissertation Ristić, Nataša M. 1975- deksametazon, fetusi, potomci, gonadotropne ćelije, jajnik, germinativne ćelije, folikuli dexamethasone, fetus, offspring, gonadotropic cells, ovary, germinative cells, follicles Datum odbrane: 5.11.2012. Tokom fetalnog razvića organizam prolazi kroz “kritične periode”, tokom kojih se dešavaju intenzivne ćelijske deobe, razvijanje i sazrevanje tkiva, organa i organskih sistema. Sredina u kojoj fetus raste i razvija se u velikoj meri odreñuje kvalitet razvojnog procesa, a svaka promena uslova dovodi do čitavog niza poremećaja, koji mogu biti praćeni smanjenjem fetalnog rasta ili IUGR (eng. Intrauterine growth retardation). Posledice IUGR su dugotrajne i ispoljavaju se u vidu različitih metaboličkih i kardiovaskularnih oboljenja u kasnijem životu. Fetalno okruženje na taj način odreñuje adultni fenotip, a njihova povezanost proučava se u okviru koncepta programiranja. Najčešće korišćeni eksperimentalni pristupi u proučavanju programiranja i efekta IUGR su dijeta majke koja vodi pothranjenosti, izazivanje stresne reakcije kod majke ili primena antenatalne terapije glukokortikoidima. Svaki od ovih eksperimentalnih modela različitim mehanizmima dovodi do izlaganja fetusa povećanoj koncentraciji glukokortikoida, koji u velikoj meri mogu da poremete fiziološki tok razvojnog procesa. Cilj ove studije je bio da se ustanovi da li je izlaganje fetusa pacova od 16. do 18.dana gestacije sintetičkom glukokortikoidu deksametazonu programiralo razvoj i funkciju hipofizno-ovarijalnog sistema od fetalnog do peripubertalnog perioda života. Predmet istraživanja u ovoj doktorskoj disertaciji bili su fetusi i ženke pacova koje su od 16. do 18. dana gestacije izloženi deksametazonu. Gravidne ženke pacova su tri uzastopna dana (od 16. do 18. dana gestacije) subkutano tretirane deksametazonom (Dexamethasonis phosphat - Dx, Krka, p.o., Novo Mesto) rastvorenom u fiziološkom rastvoru (0.9% NaCl), u dozi od 1.0, 0.5 i 0.5 mg Dx/kg... During fetal development an organism undergoes “critical periods” of intensive cell division as well as the growth and maturation of tissues, organs and organ systems. The fetal environment principally determines the quality of the developmental process, while variation of conditions may lead to a range of disorders followed by intrauterine growth retardation (IUGR). The consequences of IUGR are long-lasting and manifest through various metabolic and cardiovascular issues in later life. Thus, the fetal environment prejudices the adult phenotype, while their intertwining is elaborated with the programming concept. The most widely exploited experimental approaches in the field of programming and IUGR effects are maternal diet leading to offspring malnutrition, provoking stress to mother and antenatal glucocorticoid therapy. Each of these experimental approaches via different mechanisms leads to fetal exposure to elevated glucocorticoid levels, which may disrupt to a great extent the physiology of the developmental process. The aim of this study was to establish whether the exposure of rat fetuses to synthetic glucocorticoid dexamethasone, during the period between days 16 and 18 of gestation, programmed the development and function of the pituitary-ovarian system, starting from the fetal to the peripubertal period of life. The subject of this doctoral thesis investigation were rat fetuses and females exposed to dexamethasone from the 16th to the 18th gestational day. During three consecutive days (16–18 days of gestation) pregnant rat females were subcutaneously treated with dexamethasone (Dexamethasonis phosphate – Dx, Krka, p.o., Novo Mesto) dissolved in saline (0.9% NaCl), in doses of 1.0, 0.5 and 0.5 mg Dx/kg... Univerzitet u Beogradu Biološki fakultet Koko, Vesna. 1947- Milošević, Verica Nestorović, Nataša. 1972-( 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=76 https://fedorabg.bg.ac.rs/fedora/get/o:3475/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024526770 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:79 2013-02-25T00:00:00Z 1

Kateholamini kao medijatori delovanja muških polnih hormona na timopoezu : Catecholamines as mediators of male gonadal hormone action on thymopoiesis : doctoral dissertation Pilipović, Ivan M., 1975- timus; timopoeza; kateholamini; β2-adrenergički receptor; hormoni testisa; sveži timusni emigranti; regulatorne T-ćelije thymus; thymopoiesis; catecholamines; β2-adrenoceptor, testicular hormones; recent thymic emigrants; regulatory T cells Datum odbrane: 3.12.2012. Danas je široko prihvaćeno mišljenje da je progresivno smanjenje efikasnosti timopoeze, koje počinje u pubertetu, kauzalno povezano sa porastom koncentracije polnih hormona. Pored toga, i koncentracija kateholamina, toničnih inhibitora timopoeze posredstvom β-adrenergičih receptora, se u timusu povećava, počevši od pubertetnog perioda. Poznato je da zrele ćelije imunskog sistema (T-limfociti, makrofage i dendritske ćelije), i različiti tipovi epitelnih ćelija, imaju sposobnost sinteze kateholamina. Konačno, u različitim tkivima, muški polni hormoni utiču na sintezu kateholamina i ispoljavanje β-adrenergičkih receptora. Ova saznanja su nužno nametnula pitanje da li timociti i/ili ćelije strome timusa poseduju sposobnost sinteze kateholamina, i, ukoliko je odgovor potvrdan, da li i u kojim tipovima ćelija timusa hormoni testisa utiču na sintezu kateholamina i/ili ispoljavanje β2-adrenergičkog receptora i time, moguće, na modulatorno delovanje kateholamina na proces timopoeze. Imajući u vidu sve prethodno navedene nalaze, postavljeni su ciljevi ove disertacije: 1) da se utvrdi da li timociti i/ili ćelije strome timusa odraslih mužjaka pacova sintetišu kateholamine, i da se precizno definišu tipovi ćelija u ovom organu koji ispoljavaju β2-adrenergički receptor, 2) da se ispita da li orhidektomija u uzrastu od 30 dana, kada je timus pacova najosetljiviji na efekte kastracije, utiče na koncentraciju kateholamina i ispoljavanje β2-adrenergičkog receptora u timusu odraslih pacova, i, ako je odgovor potvrdan, 3) da se utvrdi da li se modulatorno delovanje kateholamina na timopoezu razlikuje kod orhidektomisanih i neorhidektomisanih životinja. Nađeno je da timociti, timusne epitelne ćelije i makrofage sadrže i sintetišu kateholamine. Osim toga, subpopulacije ovih tipova ćelija, takođe, ispoljavaju β2- adrenergički receptor. Orhidektomija u uzrastu od 30 dana je smanjila koncentraciju noradrenalina u timusu odraslih životinja, usled smanjenja gustine noradrenergičkih nervnih vlakana i ćelija strome timusa koje sadrže kateholamine i sadržaja noradrenalina u njima. Pored toga, u timusu ovih životinja je detektovano i smanjenje ekspresije iRNK za β2-adrenergički receptor, kao i površinske gustine ovog receptora na membrani timocita... It is widely accepted that the progressive decline in the efficiency of thymopoiesis, starting at puberty, is causally related to increasing concentrations of gonadal hormones. In addition, thymic level of catecholamines, which act, via β- adrenoceptors, as tonic inhibitors of thymopoiesis, increases around puberty. There is a pile of evidence that mature immune cells (T-lymphocytes, macrophages and dendritic cells) as well as different types of epithelial cells, synthesize catecholamines. Furthermore, it has been shown that in various tissues male gonadal hormones affect catecholamine synthesis and β-adrenoceptor expression. These findings imposed the question whether thymocytes and/or thymic stromal cells synthesize catecholamines, and, if so, whether testicular hormones influence the synthesis of catecholamines and/or expression of β2-adrenoceptors, and possibly, consequently, the modulatory action of catecholamines on thymopoiesis. Considering all the aforementioned, the dissertation was aimed to: 1) explore whether thymocytes and/or thymic stromal cells in adult male rats synthesize catecholamines, and to define the types of thymic cells expressing β2-adrenoceptor; 2) examine whether orchidectomy at the age of 30 days, when rat thymus is the most sensitive to testicular hormone deprivation, affects catecholamine levels and β2- adrenoceptor expression in the thymus of adult rats, and, if so, 3) determine whether the modulatory effects of catecholamines on thymopoiesis differ in orchidectomized and non-orchidectomized animals. It has been found that thymocytes, thymic epithelial cells and macrophages in adult rats contain and synthesize catecholamines. In addition, it was shown that subsets of these cells also express the β2-adrenoceptors. Orchidectomy at the age of 30 days decreased the concentration of noradrenaline in the thymus of adult animals by diminishing the density of noradrenergic nerve fibers and catecholamine-containing thymic stromal cells and their noradrenaline content... Univerzitet u Beogradu Biološki fakultet Leposavić, Gordana 1955- Leposavić, Gordana 1955- Cvijić, Gordana 1948- Jasnić, Nebojša 1979- Kosec, Duško 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=79 https://fedorabg.bg.ac.rs/fedora/get/o:3481/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024549554 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:81 2013-02-25T00:00:00Z 1

Ekspresija gena za inhibitor serinskih proteinaza (BvSTI) šećerne repe (Beta vulgaris L.) i uloga u otpornosti na insekte Expression of sugar beet (Beta vulgaris L.) serine proteinase inhibitor gene (BvSTI) and the role in insect resistance : doctoral dissertation Savić, Jelena, 1977- otpornost prema insektima; Inhibitor serinskih proteinaza; BvSTI gen; Šećerna repa; Inducibilni genski promotori; transgeni duvan; Spodoptera frugiperda insect resistance; Serine proteinase inhibitor; BvSTI gene; Sugar beet; Inducible gene promoters; transgenic tobacco; Spodoptera frugiperda Datum odbrane: 21.12.2012. Biljni inhibitori proteinaza aktivno učestvuju u odbrani biljaka od insekata štetočina inhibirajući insekatske digestivne proteinaze. In planta analiza ekspresije BvSTI gena koji kodira inhibitora serinskih proteinaza urađena je sa ciljem otkrivanja uloge ovog inhibitora u otpornosti biljaka šećerne repe na insekte, kao i radi utvrđivanja potencijala ovog gena kao pogodnog kandidat-gena koji bi se biotehnološkim metodama mogao uvesti u osetljive biljne genome, čime bi se povećala njihova otpornost prema insektima štetočinama. Ekspresija BvSTI gena praćena je kod tri genotipa šećerne repe koji se odlikuju umerenom otpornošću prema larvama štetočine korena Tetanops myopaeformis Roder, F1016, F1015 i UT-8, kao i kod jednog osetljivog genotipa, F1010. Kod svih otpornih genotipova mehaničko povređivanje indukovalo je ekspresiju ovog gena, a nivo transkripcije bio je povišen u poređenju sa nivoom kod osetljivog genotipa. Najintenzivniji odgovor na povređivanje zabeležen je kod otpornih genotipova F1016 i UT-8. U listovima osetljivog F1010, ali i trećeg otpornog genotipa F1015, registrovan je samo neznatni porast u intenzitetu BvSTI transkripcije, dok je u korenovima ova dva genotipa mehaničko povređivanje dovelo do blage početne supresije u aktivnosti BvSTI gena. Akumulacija BvSTI transkripata u listovima i korenovima otpornog F1016 i osetljivog F1010 kojima su se hranile larve Spodoptera frugiperda J.E. Smith pokazala je sličan obrazac ekspresije kod oba genotipa. U poređenju sa transkripcionim obrascima dobijenim nakon mehanilčkog povređivanja, ishrana insekata dovela je do znatno sporije indukcije i slabijeg intenziteta transkripcije. Analize na proteinskom nivou pokazale su da nakon povređivanja listova dolazi do akumulacije proteina veličine 30 kDa za koji su se vezala poliklonalna BvSTI specifična antitela kako kod otpornog F1016, tako i kod osetljivog F1010 genotipa. Aktivnost BvSTI inhibitora protiv tripsina pokazana je kod F1016 korenova i listova, kao i kod F1010 listova. U F1010 korenovima aktivnost BvSTI inhibitora nije detektovana. U biotestu u kome je ispitivana otpornost pojedinačnih genotipova na larve S. frugiperda korišćena su sva četiri genotipa šećerne repe kod kojih je pokazano da povređivanje utiče na ekspresiju BvSTI gena. Larve koje su se hranile listovima sva tri otporna genotipa bile su statistički značajno lakše od larvi koje su hranile osetljivim F1010 listovima... Plant proteinase inhibitor genes are among the prime candidates suitable for insect resistance improvement in plants. Expression pattern of a sugar beet serine proteinase inhibitor gene, BvSTI, was characterized in response to mechanical and fall armyworm (Spodoptera frugiperda J.E. Smith) induced wounding. BvSTI expression was analyzed in three breeding lines moderately resistant to sugar beet root maggot (Tetanops myopaeformis Roder.) and in a susceptible line, F1010. Increased mechanical wounding induced levels of BvSTI expression were observed in all resistant lines as compared to F1010. The most intensive response to wounding was observed in resistant lines, F1016 and UT-8, with a maximum up to 4- and 2,5-fold increase of BvSTI transcript levels over non-wounded roots and leaves, respectively. In contrast, slight increase of BvSTI transcript levels in leaves and even an initial decrease in roots were observed in sensitive F1010, but also in the third resistant line, F1015. BvSTI transcript accumulation in F1016 and F1010 tissues wounded by FAW showed a similar gene expression pattern, but it was delayed and less intense than the response incited by abiotic wounding. On the protein level, BvSTI-specific polyclonal antibodies confirmed increased accumulation of the 30 kDa BvSTI protein in wounded leaves but not in roots of F1016 and F1010. Using trypsin inhibition assays, the activity of BvSTI was confirmed in F1016 roots and leaves and F1010 leaves. In F1010 roots BvSTI activity was completely lacking. To confirm the potential role of the BvSTI gene in defending mechanisms to insect pests in sugar beet the same analyzed germplasm were bioassayed for resistance to fall armyworm insects. Larvae fed sugar beet leaves from all three resistant germplasms (F1016, F1015 and UT-8) had significant reductions in larval weights as compared to larvae fed on sensitive F1010 leaves. The observed daily weight increase was also the highest in larvae from sensitive vs. resistant leaves. As the larvae entered the pupal stage, pupal sizes did not reflect the overall larval weights and all developed pupae were similar. Larvae fed on roots were almost double lighter than larvae from leaves for all analyzed gemplasms. Some developmental abnormalities of the pupae fed on F1016 and F1015 leaves were noted... Univerzitet u Beogradu Biološki fakultet Ninković, Slavica Radović, Svetlana, 1958- Smigocki, Ann 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=81 https://fedorabg.bg.ac.rs/fedora/get/o:3484/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/42099471 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:86 2013-03-01T00:00:00Z 1

Hromozomska, mikrosatelitska i mitohondrijalna DNK varijabilnost populacija Drosophila subobscura u klisurama i kanjonima Srbije Chromosomal, microsatellite and mitochondrial DNA variability of Drosophila subobscura population from gorges and canyons in Serbia : doctoral dissertation Jelić, Mihailo Đ. 1982- Drosophila subobscura, pribežište, inverzioni polimorfizam, mikrosateliti, mtDNK, cito-nukleusne koadaptacije Drosophila subobscura, refugia, inversion polymorphism, microsatellites, mtDNA, cyto-nuclear coadaptations Datum odbrane: 1.12.2012. Drosophila subobscura je vrsta sa širokim Palearktičkim rasprostranjenjem. Naseljava gotovo ceo evropski kontinent, severnu Afriku, Malu Aziju i neka atlanska ostrva. Genetička struktura prirodnih populacija ove vrste je opisana upotrebom nekoliko genetičkih markera. Najtemeljnije je izučena varijabilnost hromozomskog inverzionog polimorfizma, po kome populacije D. subobscura pokazuju prostornu i vremensku struktuiranost. Klinalni obrasci ovog tipa varijabilnosti upućuju na značaj selektivnih procesa u njenom oblikovanju, dok razlike između geografski bliskih područja između kojih postoji geografska barijera upućuju na značaj istorijskih procesa. Naime, uočena varijabilnost oslikava procese rekolonizacije Evrope nakon završetka poslednje glacijacije iz primarnog pribežišta lociranog u regionu koji obuhvata Balkan, Malu Aziju i Kavkaz, ali i sekundarnog u regionu Pirinejskog poluostrva. Mikrosatelitska varijabilnost izučavana je u nekoliko evropskih populacija D. subobscura, uglavnom iz zapadnog dela Evrope. Pokazano je da su populacije slabo struktuirane po ovom genetičkom markeru. Populacije u južnom delu areala odlikuju se nešto većom genetičkom raznovrsnošću. Donekle je slična i slika varijabilnosti prirodnih populacija po mitohondrijalnoj DNK (mtDNK), u slučaju koje je zabeležena homogenost distribucije haplotipova između populacija. U velikoj većini do sada analiziranih populacija zabeleženo je prisustvo dva dominantna haplotipa i veliki broj endemičnih haplotipova niske učestalosti. Pokazano je da nekoliko faktora oblikuje varijabilnost mtDNK D.subobscura. Među njima su najznačajniji istorijski procesi, genetički drift, i prirodna selekcija koja najverovatnije deluje preko cito-nukleusne koadaptacije između alelskih kombinacija u okviru inverzija i mtDNK varijanti... Drosophila subobscura shows a wide Palearctic distribution. It inhabits most of Europe, Northern Africa, Asia Minor and some Atlantic islands. The genetic structure in natural populations of this species has been extensively studied with respect to several genetic markers. The variability of chromosomal inversion polymorphism has been most thoroughly studied showing spatial and temporal structure in natural populations. The clinal pattern of chromosomal variability suggests the action of natural selection on inversion polymorphism, while abrupt changes in gene arrangement frequencies between closely related populations separated by geographical barrier suggest the importance of historical processes on the genetic structure. After the decay of the ice caps, Drosophila subobscura, most probably, recolonized Europe mainly from the Balkan Peninsula, Asia Minor and Caucasus, but also, to a lesser degree, from the Iberian Peninsula. Several populations of D. subobscura, mostly from the Western Europe, have been studied with respect to microsatellite variability. The analysis showed absence of structuring of genetic variation, with slightly higher genetic variability in Southern populations. There is a widespread genetic homogeneity of mitochondrial DNA (mtDNA) variability throughout the species range with high prevalence of two almost equally frequent haplotypes, and a number of population specific, rare haplotypes. Several factors account for the observed distribution in mtDNA variability: historical processes, genetic drift and natural selection, most probably acting through cytonuclear coadaptation of alleles inside inversions and mtDNA haplotypes... Univerzitet u Beogradu Biološki fakultet Anđelković, Marko. 1945- Stamenković-Radak, Marina 1958-( Kurbalija-Novičić, Zorana Ludoški, Jasmina 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=86 https://fedorabg.bg.ac.rs/fedora/get/o:3490/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024538802 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:87 2013-03-01T00:00:00Z 1

Izolacija i karakterizacija bioaktivnih sekundarnih metabolita iz odabranih sojeva roda Streptomyces Isolation and characterization of bioactive secondary metabolites from selected Streptomyces strains : doctoral dissertation Stanković, Nada N. 1972- bioaktivna jedinjenja, sekundarni metaboliti, Streptomyces, pigmenti, undecilprodigiozin, izoalkanske masne kiseline, biciklični peptidi, Streptomyces durmitorensis, PKS bioactive compounds, secondary metabolites, Streptomyces, pigments, undecylprodigiosine, iso-branched fatty acids, bicyclic peptides, Streptomyces durmitotensis, PKS Datum odbrane: 6.12.2012. Actinomycetes are Gram-positive soil bacteria known as producers of secondary bioactive metabolites. In the search for new bioactive compounds collection of actinomycetes from the Laboratory for Microbial Molecular Genetics and Ecology (Institute of Molecular Genetic and Genetic Engineering, University of Belgrade) was screened according to several criteria - bioactivity, the presence of the genes for polyketide synthase (PKS), pigmentation, and crude culture extracts absorption profile in ultraviolet and visible (UV/Vis) spectra. Based on these we have isolated three strains NP10, JS520, and Streptomyces durmitotensis, previously renewed for didehydroroflamicoin (DDHR) production. Isolates NP10 and JS520 were identified to belong to the genus Streptomyces. Streptomyces sp. NP10 accumulated branched chain fatty acids, predominately isopalmitic, and cyclic dipeptides consisting of proline in combination with valine, isoleucine or alanine, that have a stimulating effect on the trophoblast cell line in culture at low concentrations (1 ng/ml and 1 mg/ml) and cytotoxic effect at high concentrations (1 mg/ml). Streptomyces sp. JS520 was determined to be exceptionally good producer of pigment undecylprodigiosine (UP) with antibacterial, antifungal, antioxidant and UV protective activities showing cytotoxic effects on trophoblast cell line in culture at high concentrations (1 ng/ml). Cytotoxicity of polyene macrolide antibiotic DDHR from S. durmitotensis was confirmed and it’s antifungal effects were shown. PKS cluster responsible for DDHR synthesis was subcloned in the cosmid library and partially sequenced. Optimization of culture conditions resulted in 2.12 times increased production of UP, and 1.1 times increased production of DDHR. Actinomycetes are Gram-positive soil bacteria known as producers of secondary bioactive metabolites. In the search for new bioactive compounds collection of actinomycetes from the Laboratory for Microbial Molecular Genetics and Ecology (Institute of Molecular Genetic and Genetic Engineering, University of Belgrade) was screened according to several criteria - bioactivity, the presence of the genes for polyketide synthase (PKS), pigmentation, and crude culture extracts absorption profile in ultraviolet and visible (UV/Vis) spectra. Based on these we have isolated three strains NP10, JS520, and Streptomyces durmitotensis, previously renewed for didehydroroflamicoin (DDHR) production. Isolates NP10 and JS520 were identified to belong to the genus Streptomyces. Streptomyces sp. NP10 accumulated branched chain fatty acids, predominately isopalmitic, and cyclic dipeptides consisting of proline in combination with valine, isoleucine or alanine, that have a stimulating effect on the trophoblast cell line in culture at low concentrations (1 ng/ml and 1 mg/ml) and cytotoxic effect at high concentrations (1 mg/ml). Streptomyces sp. JS520 was determined to be exceptionally good producer of pigment undecylprodigiosine (UP) with antibacterial, antifungal, antioxidant and UV protective activities showing cytotoxic effects on trophoblast cell line in culture at high concentrations (1 ng/ml). Cytotoxicity of polyene macrolide antibiotic DDHR from S. durmitotensis was confirmed and it’s antifungal effects were shown. PKS cluster responsible for DDHR synthesis was subcloned in the cosmid library and partially sequenced. Optimization of culture conditions resulted in 2.12 times increased production of UP, and 1.1 times increased production of DDHR. Univerzitet u Beogradu Biološki fakultet Vasiljević, Branka Fira, Đorđe. 1959- Vasiljević, Branka Fira, Đorđe Nikodinović-Runić, Jasmina 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=87 https://fedorabg.bg.ac.rs/fedora/get/o:3492/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024553906 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:88 2013-03-01T00:00:00Z 1

Florističko-ekološka analiza silikatnih algi (Bacillariophyta) reke Nišave i pritoka Jerme i Temske Floristic-ecological analysis of (Bacillariophyta) from the Nišava river and tributaries Jerma and Temska rivers : doctoral dissertation Andrejić, Jelena Z. 1983- Silikatne alge, floristički sastav, sezonska dinamika, Nišava, Jerma, Temska, TDI Diatoms, floristic composition, seasonal dymanics, Nišava, Jerma, Temska, TDI Datum odbrane: 6.12.2012. Florističko-ekološka analiza silikatnih algi reke Nišave i pritoka Jerme i Temske realizovana je sa ciljem da se utvrdi floristički sastav i sezonska dinamika zajednice silikatnih algi i da se proceni kvalitet vode ovih reka na osnovu TDI (Trophic Diatom Index). Algološki materijal je sakupljan od maja 2008. godine do maja 2009. godine, na 11 lokaliteta u reci Nišavi i po jednom lokalitetu u rekama Jermi i Temskoj. Osnovni fizičko-hemijski parametri vode su mereni na svakom lokalitetu. Uzorci silikatnih algi su u laboratoriji tretirani jakim kiselinama, zatim zatopljeni u sintetičku smolu i posmatrani pod svetlosnim mikroskopom. Fizičko-hemijske analize vode reke Nišave ukazuju na povećanje koncentracije nutrijenata (amonijum jona, nitrata, nitrita) na lokalitetima posle Dimitrovgrada, Bele Palanke, Pirota i Niša. Izmerena vrednost pH vode na većini lokaliteta je u granici od 6 do 7. Ove vrednosti su niže od očekivanog slabo baznog karaktera vode za slivno područje Nišave. Analizom florističkog sastava u sve tri reke utvrđena su ukupno 194 taksona, svrstanih u 58 rodova. Taksonima najbrojniji rodovi su Navicula (24), Nitzschia (17) i Gomphonema (13). U reci Nišavi utvrđeno je 177 taksona, u Jermi 115 i u Temskoj 93. Dva taksona (Navicula novaesiberica i Neidiomorpha binodiformis) predstavljaju nove nalaze za floru silikatnih algi Srbije Sezonska dinamika silikatnih algi u Nišavi, Jermi i Temskoj i njihova procentualna zastupljenost u epilitnoj zajednici u ispitivanom periodu, zavise od koncentracije nutrijenata i temperature vode. Zapažamo smenu zajednica silikatnih algi. U prolećnoj sezoni dominiraju predstavnici roda Achnanthidium... Floristic and ecological analysis of the diatoms from the Nišava River and tributaries Jerma and Temska Rivers was conducted to determine the floristic composition and seasonal dynamics of diatom communities as well as to evaluate the water quality of these rivers based on the TDI (Trophic Diatom Index). Algological material was collected from May 2008 until May 2009 at 11 sampling sites in the Nišava River and one site in the Jerma and Temska Rivers. Basic physico-chemical properties of the water were measured at each sampling site. In the laboratory diatom samples were treated with strong acids, then mounted in a synthetic medium and examined with a light microscope. Physico-chemical analysis of the water of the Nišava River indicated an increase in nutrient concentration (ammonium ions, nitrate, nitrite) at sites located downstream of Dimitrovgrad, Bela Palanka, Pirot and Niš cities. The majority of sampling sites had pHs that ranged from 6 to 7. These pHs were lower than the weakly alkaline values expected for the Nišava River catchment area. Analysis of the floristic composition of the three rivers determined a total of 194 taxa grouped in 58 genera. The genera with the most numerous taxa were Navicula (24), Nitzschia (17) and Gomphonema (13). In total, 177 taxa were identified in the Nišava River, 115 in the Jerma River and 93 taxa in the Temska River. Two taxa (Navicula novaesiberica and Neidiomorpha binodiformis) were new findings for the Serbian diatom flora. The seasonal dynamics of diatoms in the Nišava, Jerma and Temska Rivers and their proportional representations in epilithic communities depended on the concentration of nutrients and water temperature. A seasonal shift of diatom communities was noticed. The spring season was dominated by taxa from the genus Achnanthidium... Univerzitet u Beogradu Biološki fakultet Krizmanić, Jelena, 1971- Cvijan, Mirko, 1950- Simić, Snežana, 1966- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=88 https://fedorabg.bg.ac.rs/fedora/get/o:3494/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/42097935 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:91 2013-03-05T00:00:00Z 1

Ekspresija gena za inhibitore cisteinskih proteinaza (OCI i OCII) u transformisanim biljkama krompira (Solanum tuberosum L.) Expression of cysteine proteinase inhibitor genes (OCI and OCII) in transformed potato (Solanum tuberosum L.) plants Cingel, Aleksandar, 1969- „slaganje“ gena; ko-transformacija; re-transformacija; krompir; inhibitori cisteinskih proteinaza; orizacistatin I; orizacistatin II; otpornost prema insektima; krompirova zlatica; kompenzatorni odgovori insekata gene stacking; co-transformation; re-transformation; potato; cysteine proteinase inhibitors; oryzacystatin I; oryzacystatin II; insect resistance; Colorado potato beetle; insect compensatory response Datum odbrane: 6.12.2012. Kombinovanje ili “slaganje” različitih gena u transgenim biljkama radi postizanja uspešnije kontrole patogena i štetočina i/ili većeg prinosa predstavlja jednu od glavnih oblasti istraživanja savremene biotehnologije. Orizacistatini I i II (OCI i OCII), proteinazni inhibitori različitih specifičnosti, pokazali su potencijal u kontroli štetočina koje koriste cisteinske proteinaze za digestiju proteina. Da bi se pojačao njihov inhibitorni potencijal i, eventualno, povećala efikasnost ovih inhibitora u kontroli štetočina, oba cistatina su koeksprimirana u transformisanim biljkama tri sorte krompira. “Slaganje” orizacistatinskih gena kod sorti Dragačevka i Dezire ostvareno je postupkom ko-transformacije i zabeležena je frekvenca kointegracije OCI i OCII gena od 20-22%. Kod sorte Jelica sekvencijalna re-transformacija se pokazala kao efikasniji pristup: frekvenca integracije OCII gena nakon re-transformacije OCI-transformisane linije iznosila je 91%. Istovremeno, “slaganje” dva orizacistatnska gena, bilo postupkom ko- ili re-transformacije, postignuto je upotrebom nptII gena kao jedinog selekcionog markera. Ekspresija OCI i OCII gena indukovana povređivanjem i akumulacija biološki aktivnih rekombinantnih OCI i OCII proteina potvrđena je kod svih analiziranih OCI/OCII transformisanih linija krompira. OCI/OCII linije krompira nisu ispoljavale značajna odstupanja od normalnog fenotipa, što ukazuje na nizak nivo somaklonalnih varijacija i odsustvo uticaja rekombinantnih OCI i OCII na metabolizam biljke domaćina. Iako nije uticala na preživljavanje, ishrana larvi krompirove zlatice (Leptinotarsa decemlineata Say) listovima krompira koji eksprimiraju oba orizacistatina imala je značajan uticaj na različite osobine performanse rasta i razvića larvi. Larve hranjene transformisanim listovima su se presvlačile ranije, i tokom L2 i L3 stupnja uvećavale masu do 29,7% brže i konzumirale listove do 29,1% brže u odnosu na one hranjene netransformisanim listovima. Istovremeno, larve na OCI/OCII listovima su do tri dana ranije dostizale maksimum mase i ranije “usporavale” sa ishranom ulazeći u prepupalnu fazu razvića. Uprkos povećanju performansi rasta i ishrane, pri istoj efikasnosti ishrane, L4 larve na transformisanim listovima nisu u potpunosti uspele da kompenzuju negativne efekte prisustva orizacistatina u hrani. U odnosu na larve hranjene netransformisanim listovima, maksimalna masa na kraju larvenog razvića i ukupan stepen oštećenja listova bili su do 19,4% i do 18,5% manji kod larvi krompirove zlatice hranjenih OCI/OCII transformisanim listovima krompira. Smanjenje mase larvi na OCI/OCII listovima dovelo je i do pojave adulta krompirove zlatice sa do 26,3% redukovanom telesnom masom. Analiza ukupne proteinazne... The combination or stacking different genes in transgenic plants to achieve disease and pest control and/or higher crop yield is one of a major method of contemporary biotechnology. Oryzacystatins I and II (OCI and OCII), inhibitors with different specificity, show potential in controlling pests that utilize cysteine proteinases for protein digestion. To strengthen this inhibitory range and, possibly, achieve an additive effect in the overall efficiency of these proteins against pests, both cystatins were co-expressed in three potato cultivars. Oryzacystatin genes pyramiding in Dragačevka and Desiree cultivars were achieved by co-transformation with OCI and OCII genes co-integration frequency of 20-22%. For Jelica cultivar sequential re-transformation was more efficient approach: OCII gene integration frequency following re-transformation of an OCI-expressing line was 91%. Additionally, pyramiding of different oryzacystatin genes, by co- or re-transformation approach, were achieved using the nptII gene as the only selection marker. Wounding induction of OCI and OCII gene transcripts and accumulation of biologically active OCI and OCII recombinant proteins was confirmed in all analyzed OCI/OCII transformed lines. OCI/OCII potato lines did not exhibit morphological abnormalities, indicating low level of somaclonal variation or interference of the recombinant OCI or OCII with host plant metabolism. In the absence of significant mortality, feeding Colorado potato beetle larvae (Leptinotarsa decemlineata Say) on OCI/OCII-expressing foliage had an impact on various aspects of the growth and developmental performances of larvae. Larvae feeding on transformed potato leaves tended to molt earlier and, especially during L2-L3 stages, gain weight up to 29.7% faster and consume leaf material up to 29.1% faster, compared to those on untransformed foliage. Larvae on OCI/OCII foliage were also reach maximum weight gained three days earlier and slow down earlier in preparation for pupation. Despite their faster growth and feeding, with similar efficiencies of conversion of ingested food, L4 larvae reared on transformed foliage were not compensating presence of the recombinant oryzacystatins in the diet.Compared to those on untransformed foliage, maximum weight gained and amount of foliage consumed were up to 19.4% and 18.5%, respectively, lower for the larvae fed on OCI/OCII potato foliage. Larval weight reduction on OCI/OCII foliage resulted in adult emergence with up to 26.3% reduced body mass. Analysis of total digestive proteinases activity showed initially, up to 56%, reduction in digestive capacity... Univerzitet u Beogradu Biološki fakultet Ninković, Slavica Radović, Svetlana Lazarević, Jelica Miljuš-Đukić, Jovanka 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=91 https://fedorabg.bg.ac.rs/fedora/get/o:3499/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/42095119 sr Autorstvo 3.0 Srbija (CC BY 3.0)

oai:eteze.bg.ac.rs:92 2013-03-05T00:00:00Z 1

Uticaj trombina na regulaciju proliferacije glatkih mišićnih ćelija aorte pacova Effects of trombin in the regulation of rat's aortic smooth muscle cells proliferation : doctoral dissertation Smiljanić, Katarina trombin, VSMC, proliferacija, ADAM 12, MMP-2, PKCδ, ERK1/2, HB-EGF, ateroskleroza Thrombin, VSMC, Proliferation, ADAM 12, MMP-2, PKCδ, EGFR, ERK1/2, HB-EGF, Aterosclerosis Datum odbrane: 22.10.2012. Kardiovaskularne bolesti predstavljaju najveći uzrok smrtnosti ljudske populacije, a njihova glavna i osnovna patološka komponenta je ateroskleroza. Proliferacija ili deoba glatkih mišićnih ćelija krvnog suda (VSMC) ključni je događaj u nastanku raznih vaskularnih oboljenja, uključujući aterosklerozu i hipertenziju. U procesu diferencijacije i abnormalne deobe VSMC povezanih sa hipertenzijom i aterosklerozom uključen je i trombin. Stimulisanje VSMC trombinom dovodi do aktivacije ekstracelularnim signalima regulisanih kinaza 1 i 2 (ERK1/2), preko transaktivacije receptora za epidermalni faktor rasta (EGFR). U ranijim studijama Isenović i saradnici potvrdili su na osnovu inhibicije ERK1/2 od strane PD9805 inhibitora, učešće ERK1/2 u regulaciji proliferacije VSMC izazvanoj trombinom. U nastavku, faktor rasta sličan epidermalnom faktoru rasta koji vezuje heparin (HB-EGF), protein kinaza C delta (PKCδ) i matriksne metaloproteinaze (MMP), nađene su u VSMC i pokazano je da je i njihova aktivnost regulisana trombinom. ADAM (engl. “A Disintegrin And Metalloproteinase”) transmembranske su metaloproteinaze koje pripadaju adamalizinskoj grupi i razlikuju se od matriksnih metaloproteinaza po tome što imaju vanćelijski dizintegrinski i citoplazmatski domen. C terminalni domen može da stupa u interakciju sa unutarćelijskim proteinima. Uvidom u literaturu, do sada ne postoji istraživanje koje ukazuje na prisustvo ADAM metaloproteinazne aktivnosti vezane za proliferaciju VSMC stimulisane trombinom. Predmet ove doktorske teze jeste proučavanje uloge EGFR, ERK1/2, HB-EGF, PKCδ, ukupnih metaloproteinaza, kao i specifičnih MMP-2 i ADAM 12, u posredovanju proliferativnog efekta trombina na VSMC pacova. Inkubacija VSMC pacova sa trombinom (1 U/ml) u periodu od 5 minuta rezultirala je u značajnom povećanju: fosforilacije ERK1/2 od 8.7 ± 0.9 puta (p<0.001), fosforilacije EGFR od 8.5 ± 1.3 puta (p<0.001) i sinteze DNK od 3.6 ± 0.4 puta (p<0.001). Prethodni pojedinačni tretmani ovih ćelija u trajanju od 30 minuta sa 10 μM PD169540 (PD), ireverzibilnim inhibitorom EGFR, i 20 μM antitelom protiv HB-EGF značajno su smanjili trombinom stimulisanu fosforilaciju EGFR za 81 % i 72 % i ERK1/2... ardiovascular disease is the largest single cause of mortality and its major underlying pathology is atherosclerosis. The proliferation of vascular smooth muscle cells (VSMC) is a key event in the pathogenesis of various vascular diseases, including atherosclerosis and hypertension. Thrombin is involved in the differentiation and abnormal proliferation of VSMC associated with atherosclerosis and hypertension. Thrombin stimulation results in extracellular signal-regulated kinase (ERK 1/2) activation through transactivation of the epidermal growth factor receptor (EGFR). Based on the studies in which PD98059 used to inhibit ERK1/2, we have shown previously that ERK1/2 was involved in the regulation by thrombin of VSMC’s proliferation. In addition, heparin-binding EGF-like growth factor (HB-EGF) and matrix metalloproteinases (MMPs) have also been detected in VSMC and shown to be regulated by thrombin. ADAMs (A Disintegrin And Metalloproteinase) are transmembrane metalloproteinases, belonging to adamalysin group, that are distinct from matrix metalloproteinases (MMPs) in that, they have an extracellular disintegrin domain and cytoplasmic domain that can associate with intracellular proteins. To the present knowledge there is no study that indicates the activation of an ADAM member in thrombin-induced VSMC proliferation. In this dissertation, the role of EGFR, ERK1/2, HB-EGF, general metalloproteinases, MMP-2 and ADAM 12, as well as PKCδ in mediating the mitogenic action of Thrombin in rat VSMC was investigated. Incubation of rat VSMC with Thrombin (1 U/ml) for 5 minutes resulted in significant increase of ERK1/2 phosphorylation by 8.7 ± 0.9 fold (p<0.001), EGFR phosphorylation by 8.5 ± 1.3 fold (p<0.001) and DNA synthesis by 3.6 ± 0.4 fold (p<0.001). Separate pretreatments for 30 minutes with EGFR tyrosine kinase irreversible inhibitor, 10 μM PD169540 (PD), and 20 μM anti-HB-EGF antibody, significantly reduced thrombinstimulated EGFR and ERK1/2 phosphorylation by 81 %, 72 % and by 48 % and 61%, respectively. Furthermore, same pretreatments with PD and anti-HB-EGF antibody reduced Thrombin-induced VSMC’s proliferation by 44% and 45%, respectively. In addition, pretreatments for 30 minutes with 10 μM KB-R7785 (KB), a specific ADAM 12 inhibitor or 10 μM specific MMP2 inhibitor significantly reduced thrombin-stimulated EGFR.. Univerzitet u Beogradu Biološki fakultet Isenović, Esma 1962- Isenović, Esma. 1962- Đorđević, Jelena, 1964- Đorđević, Jelena, 1964- Putniković, Biljana, 1954- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=92 https://fedorabg.bg.ac.rs/fedora/get/o:3502/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024530866 sr Autorstvo 3.0 Srbija (CC BY 3.0)

oai:eteze.bg.ac.rs:93 2013-09-30T00:00:00Z 1

Transkripciona regulacija ekspresije humanog SOX18 gena Transcriptional regulation of the human SOX18 gene expression : doctoral dissertation Petrović, Isidora, 1976- SOX18, transkripcija, promotor, transkripcioni faktor, endotelijalne ćelije, angiogeneza SOX18, transcription, promoter, transcription factor, endothelial cells, angiogenesis Datum odbrane: 5.12.2012. Humani SOX18 gen pripada familiji SOX gena koji kodiraju DNK-vezujuće proteine koji imaju ulogu transkripcionih faktora i arhitektonskih komponenti hromatina. SOX18 gen ima važnu ulogu u regulaciji vaskularnog razvića, i učestvuje u specifikaciji i diferencijaciji endotelijalnih ćelija, angiogenezi i limfangiogenezi. Mutacije u SOX18 genu kod čoveka su povezane sa sidromom Hipotrihoza-Limfedem-Talengiektazija (eng. Hypotrichosis-Lymphedema-Talengiectasia) čije su karakteristike poremećaji u razviću dlake, vaskularnog i limfnog sistema. Iako do danas ima dosta podataka o ulozi SOX18 gena u procesima vaskularogeneze, angiogeneze i limfangiogeneze, još uvek se malo zna o molekularnim mehanizmima uključenim u regulaciju ekspresije ovog gena. Osnovni ciljevi, istraživanja predstavljenog u ovoj tezi, bili su analiza transkripcione regulacije ekspresije humanog SOX18 gena, kao i analiza uticaja pro-angiogenetskih faktora i inhibitora angiogeneze na ekspresiju ovog gena u endotelijalnim ćelijama. Ispitivanja transkripcione regulacije su obuhvatala analizu uloge određenih transkripcionih faktora u regulaciji aktivnosti SOX18 promotora, kao i u regulaciji endogene ekspresije SOX18 gena. Transkripciona regulacija je ispitivana u dva model sistema: HeLa ćelijama, koje su korišćena kao tumorski model sistem i EA.hy926 ćelijama, koje su korišćene kao endotelijalni model sistem. In silico analizom su identifikovana potencijalna vezivna mesta za različite transkripcione faktore koji mogu biti uključeni u regulaciju ekspresije SOX18 gena. Za dalju funkcionalnu analizu odabrani su transkripcioni faktori Sp3, ZBP-89, NF-Y i EGR1. Na osnovu eksperimenata smanjene elektroforetske pokretljivosti, funkcionalnih/mutacionih analiza, i analiza ekspresije u nativnom kontekstu, pokazano je da su transkripcioni faktori Sp3 i ZBP-89 negativni, a NF-Y i EGR1 pozitivni regulatori transkripcije humanog SOX18 gena. Na ovaj način pokazana je funkcionalna veza između transkripcionih faktora Sp3, ZBP-89, NF-Y i EGR1 i SOX18 gena i omogućeno je bolje razumevanje, dela, transkripcione kontrole ekpresije ovog gena... Human SOX18 gene belongs to the family of SOX genes that encode DNA-binding proteins, which display properties of both transcription factors and architectural components of chromatin. SOX18 gene plays important role in vascular development, endothelial cell specification and differentiation, angiogenesis and lymphangiogenesis. Mutations in human SOX18 gene are associated with Hypotrichosis-Lymphedema-Talengiectasia syndrome, characterized by defects in hair, vascular and lymphatic development. Despite the mounting evidence that SOX18 gene is an important player in vasculogenesis, angiogenesis and lymphangiogenesis, little is known about molecular mechanisms involved in the regulation of its expression. The aim of this study was to investigate transcriptional regulation of the human SOX18 gene expression, as well as the effecs of pro- and anti-angiogenic factors on SOX18 expression in endothelial cells. Analyses of transcriptional regulation included identification of transcription factors that are involved in regulation of SOX18 promoter activity, as well as in regulation of endogenous SOX18 expression. Two model systems were used: HeLa cells, as a tumor model system, and EA.hy926 cells, as an endothelial model system. Several putative transcription factor binding sites were identified by in silico analysis of the SOX18 promoter sequence. Transcription factors Sp3, ZBP-89, NF-Y and EGR1 were selected for further functional analysis. By in vitro binding assays, functional/mutagenesis assays and analyses of endogenous SOX18, it has been shown that transcription factors Sp3 and ZBP-89 act as negative regulators, while NF-Y and EGR1operate as positive regulators of SOX18 gene expression. These results gave first functional link between Sp3, ZBP-89, NF-Y and EGR1 transcription factors and SOX18 gene, thus providing better understanding of transcriptional regulation of SOX18 gene expression... Univerzitet u Beogradu Biološki fakultet Stevanović, Milena Stevanović, Milena Brajušković, Goran. 1968- Brajušković, Goran. 1968- Radović, Svetlana. 1958- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=93 https://fedorabg.bg.ac.rs/fedora/get/o:3503/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024552370 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:94 2013-03-05T00:00:00Z 1

Efekti kombinovane transkranijalne magnetne stimulacije i deprivacije spavanja u tretmanu major depresija Effects of combined transcranial magnetic stimulation and sleep deprivation in the treatment of major depression : doctoral dissertation Krstić, Jelena D. 1971- major depresija, repetitivna transkranijalna magnetna stimulacija, deprivacija spavanja, BDNFVal66Met genetički polimorfizam major depression, repetitive transcranial magnetic stimulation, sleep deprivation, BDNF Val66Met genetic polymorphism Datum odbrane: 12.12.2012. Cilj rada. Cilj ovog rada je procena efekata kombinovane primene repetitivne transkranijalne magnetne stimulacije (rTMS) niske frekvencije (1 Hz) i parcijalne deprivacije spavanja (PDS) kod osoba obolelih od major depresije, koje prethodno pokazuju nezadovoljavajući odgovor na dva različita antidepresiva (ispunjavaju kriterijume terapijske rezistencije). Uporedo sa dugoročnim praćenjem (do 6 meseci) efekata ovog tretmana, analiziran je i genetički BDNF Val66Met polimorfizam, kao mogući perimisivni faktor plasticiteta odgovoran za predikciju efikasnosti primenjenih terapijskih strategija. Ispitanici i metode. Ukupno 20 osoba obolelih od major depresije, koje su ispunjavale kriterijume terapijske rezistencije tretirano je na navedeni način kombinacijom rTMS i PDS, uporedo sa njihovom prethodnom medikamentoznom terapijom. Kombinovani protokol rTMS i PDS sprovodio se tokom dve uzastopne nedelje, i za to vreme su ispitanici svakog dana, izuzev pauze za vikend dobijali stimulaciju rTMS (frekvencija 1 Hz, intenzitet 110% praga izazivanja motornog odgovora) primenjivanu iznad desnog dorzolateralnog prefrontalnog korteksa (DLPFK), u jutarnjim časovima. U svakoj nedelji po jednom, opisanoj rTMS, prethodila je redukcija noćnog spavanja uz buđenje u pola 2. Ispitanici su randomski podeljeni u grupu koja je primala rTMS+PDS i grupu koja je primala placebo (sham) rTMS stimulaciju + PDS. Procene efekta vršene su standardnim instrumentima kliničke procene (modifikovana Hamiltonova skala za procenu depresivnosti - HDRS-24; Montgomery-Asberg skala za procenu depresivnosti - MADRS, i skala opšteg kliničkog utiska), i to: pre početka primene protokola, neposredno po završetku, jednu nedelju kasnije, tri i šest meseci kasnije (dugoročna praćenja sprovedena su isključivo kod ispitanika koji su bili podvrgnuti aktivnom tretmanu). Rezultati. Primenjeni protokol stimulacije pokazao je antidepresivni efekat, kod osoba obolelih od unipolarne depresije na nepromenjenoj dozi antidepresivnih lekova koji se održavao tokom čitavog šestomesečnog perioda praćenja. Neposredno nakon 2 nedelje protokola ispitanici koji su primali aktivni rTMS imali su prosečno poboljšanje od 39%... Objectives. The main aim of this study was to evaluate potential synergistic antidepressant effect of two therapies: repetitive transcranial magnetic stimulation (rTMS) applied at 1 Hz associated with partial sleep deprivation (PSD) in patients with treatment resistant major depression. Besides the long- term (during the next 6 months) evaluation of effecacy of this treatment, potential predictive role of brain-derived neurotrophic factor (BDNF) Val66Met genetic polymorphism in rTMS treatment response was analysed, as a factor of neuronal plasticity, also involved in patogenesis of major depression Subjects and methods Twenty patients with diagnoses of treatment resistant major depression, at fixed doses of antidepressants, were treated with combination of rTMS and PSD. rTMS was applied during two consecutive weeks (5 days/week) with frequency of 1Hz, at 110% intensity of resting motor threshold, over the right dorso-lateral prefrontal cortex (DLPFC), in the morrning hours. Partial sleep deprivation was applied once during every week, as late partial sleep deprivation (patients were woke up at 01.30 a.m.). Patients were randomly assigned to receive rTMS+PSD, or sham+PSD. Clinical evaluation was done using the following rating scales: the modified Hamilton depression rating scale (HDRS-24), Montgomery-Asberg rating scale (MADRS ) and Clinical global impression scale (CGI-S), at baseline, after 2 weeks of treatment and one week after treatment, as well as long-term follow-up (only patients treated with active rTMS). Results. Study results suggest clinically relevant response, lasted up to 6 months in patients with unipolar major depression at fixed doses of antidepressants. After 2 weeks of treatment, patients treated with active rTMS had the average improvement of 39% score reduction on HDRS... Univerzitet u Beogradu Biološki fakultet Ilić, Tihomir V. Nedeljković, Nadežda 1967- Špirić, Željko 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=94 https://fedorabg.bg.ac.rs/fedora/get/o:3504/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024553138 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:95 2013-03-06T00:00:00Z 1

Varijabilnost gena uključenih u inflamatorne, imunomodulatorne i apoptotske procese kao faktor rizika za nastanak bazocelularnog karcinoma glave i vrata Variability of genes involved in inflammatory, immunomodulatory and apoptotic process as a risk factor for head and neck basal cell carcinomas : doctoral dissertation Kostić, Marija M., 1984- bazocelularni karcinom, polimorfizmi nukleotidne sekvance, TNF-alpha, TNF receptori,MMP-9, survivin, TP53 basal cell carcinoma, single nucleotide polymorphizms, TNF-alpha, TNF receptors,MMP-9, survivin, TP53 Datum odbrane: 4.12.2012. Bazocelularni karcinom (BCK), poznat kao i bazaliom, je najčešćih oblik kancera u populaciji Kavkayijanaca... Introduction: Basal-cell carcinoma (BCC), also known as basalioma, is the most frequent tzpe of cancer among the Caucasus... Univerzitet u Beogradu Biološki fakultet Stamenković-Radak, Marina 1958- Milašin, Jelena 1957- Novaković, Ivana 1961- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=95 https://fedorabg.bg.ac.rs/fedora/get/o:3508/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024539314 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:96 2013-03-11T00:00:00Z 1

Struktura topološki zatvorene ORI sekvence dihidrofolatreduktaznog lokusa u interakciji sa inicijacionim proteinom ORC Structure of topologically closed ORI sequence from dihydrofolate reductase locus in interaction with initiation protein ORC : doctoral dissertation Tomić, Branko V., 1980- HsOrc4, ori DHFR, superspiralizacija, Topoizomeraza I, Mung Bean nukleaza HsOrc4, ori DHFR, supercoiling, Topoisomerase I, Mung Bean nuclease Datum odbrane: 24.9.2012. Replikacija je jedan od osnovnih procesa u životnom ciklusu ćelije. Cilj replikacije je udvajanje genetičkog materijala. Da bi genetički materijal bio pravilno umnožen i kasnije razdvojen na ćerke ćelije, razvijen je veliki broj mehanizama regulacije replikacije. Jedan od načina regulacije je pravilan izbor i aktivacija mesta inicijacije replikacije. Broj i kompleksnost mesta inicijacije replikacije varira među vrstama. Kod evolutivno nižih eukariota su jednostavnija, dok su kod viših eukariota kompleksnija. Način prepoznavanja ovih mesta od strane inicijacionih proteina nije u potpunosti razjašnjen. Ori sekvenca, locirana nizvodno od gena DHFR (dihidrofolat reduktaza) hrčka, sadrži tri definisana ori mesta inicijacije replikacije: ori β, ori β' i ori γ. Ori β sekvenca DHFR je jak replikator i pokazuje aktivnost na ektopičnim mestima. Premda je ori sekvenca DHFR jedna od najbolje okarakterisanih ori sekvenci kod metazoa i u okviru nje definisani funkcionalno značajni regioni (AT bogati region, DNR region, BEND, RIP60 region, IR 4 bp), njihova funkcija nije u potpunosti razjašnjena. Protein ORC (eng. Origin recognition complex) je heteroheksamer odgovoran za prepoznavanje mesta inicijacije replikacije. Pretpostavka je da nekoliko elemenata ima ulogu u prepoznavanju ori sekvence od strane ORC kompleksa kod metazoa. Funkcija ljudskog proteina Orc4 (HsOrc4) do sad nije u potpunosti razjašnjena. Našim prethodnim istraživanjima, pokazali smo da HsOrc4 prepoznaje nekanonske strukture i ima sposobnost za utiče na formiranje TAT tripleksa i homoadeninskih struktura... Replication is one of the fundamental processes in the life cycle of the cell. The aim of replication is a duplication of genetic material. To make genetic material properly duplicated and subsequently divided into daughter cells, a large number of mechanisms of regulation of replication have been developed. One way of regulation is the proper selection and activation of replication initiation. The number and complexity of the origins of replication (ori) varies among species. They are simpler at evolution lower eukaryotes, while in higher eukaryotes are more complex. The way of recognizing these places by initiation proteins is not fully understood. Ori sequence, located downstream of the DHFR gene (dihydrofolate reductase) hamster, contains three defined origins of replication: ori β, ori β' and ori γ. Ori β DHFR sequence is strong replicator and shows activity at ectopic places. Although the sequence of ori DHFR is one of the best characterized ori sequences in metazoans and within defined functionally important regions (AT rich region, DNR region, BEND, RIP60 region, IR 4 bp), their function is still not completely understood. ORC (Origin recognition complex) is heterohexamer protein responsible for identifying origins of replication. It is assumed that several elements play a role in recognizing ori sequences of the ORC complex in metazoans.The function of the human protein Orc4 (HsOrc4) has not been fully elucidated. Our previous studies showed that HsOrc4 recognize non-canonical structures and has the ability to influence at formation of TAT triplexes and homoadenine structures... Univerzitet u Beogradu Biološki fakultet Kušić-Tišma, Jelena Brajušković, Goran, 1968- (ths, code: 09006) Brajušković, Goran, 1968- Stefanović, Dragana Radojković, Dragica 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=96 https://fedorabg.bg.ac.rs/fedora/get/o:3566/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024530354 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:97 2013-03-12T00:00:00Z 1

Citogenetička, palinološka i filogeografska istraživanja roda Ramonda (Gesneriaceae) na Balkanskom poluostrvu Cytogenetics, palynology and phylogeography of genus Ramonda (Gesneriaceae) in the Balkan peninsula : doctoral dissertation Lazarević, Maja R., 1976- Ramonda, Gesneriaceae, endemiti, relikti, Balkan, poliploidija, hibridi, citometrija, AFLP Ramonda, Gesneriaceae, endemics, relicts, Balkan, polyploidy, hybrids, cytometry, AFLP Datum odbrane: 8.12.2012. Familija Gesneriaceae obuhvata biljne vrste pretežno rasprostranjene u tropskim u subtropskim oblastima Starog i Novog sveta. Samo mali broj vrsta naseljava umerene oblasti, a među njima je i jedinih 5 vrsta ove familije u Evropi: Ramonda myconi, endemit Pirinejskog poluostrva, kao i R. nathaliae, R. serbica, Haberlea rhodopensis i Jankaea heldreichii, četiri endemične vrste Balkanskog poluostrva. Svih pet vrsta su relikti Tercijera, vremena kada je klima u Evropi bila toplija i vlažnija. Za vreme Ledenog doba, one su našle skrovište u klisurama i kanjonima gde ih najčešće nalazimo i danas. Ovi „živi fosili“ danas nepovoljne uticaje spoljašnje sredine u velikoj meri preživljavaju zahvaljujući poikilohidričnosti, pa se još nazivaju i „biljke koje vaskrsavaju“. Danas se dve balkanske vrste roda Ramonda odlikuju disjunktnim arealima. Ramonda nathaliae zastupljena je u Makedoniji, S Grčkoj, na obroncima planine Šare na Kosovu i u JI Srbiji. Najveći deo areala vrste R. serbica nalazi se u Albaniji, a prisutna je i na SZ Grčke, u Z Makedoniji, JZ i SI Crnoj Gori, JZ, JI i SI Srbiji, kao i na SZ Bugarske. Jedina zona u kojoj se areali dve vrste susreću nalazi se u JI Srbiji, gde na dva lokaliteta, Oblik i Radovanski Kamen, obrazuju simpatrijske populacije. Obe vrste prevashodno naseljavaju krečnjačku podlogu, s tim što se R. nathaliae može naći i na serpentinitu, škriljcima i granitu. Ova vrsta, takođe, bolje podnosi otvorenija staništa, a njene populacije se mogu naći i na većem rasponu nadmorskih visina, zbog čega se smatra otpornijom i tolerantijom. Ciljevi ovog rada su višestruki: da se utvrde morfološke osobine polena i semena sve tri vrste roda Ramonda, jer detalji njihove građe do sada nisu istraživani; da se procene vijabilnost njihovog polena i klijavost semena; da se utvrdi broj hromozoma, kao i veličina genoma kod tri vrste; da se proveri da li postoje hibridne jedinke u simpatrijskim populacijama; da se pomoću molekularnih markera utvrdi stepen sličnosti i filogeografske veze između vrsta R. nathaliae i R. serbica. U tu svrhu, polen i seme analizirani su pomoću svetlosnog i scanning elektronskog mikroskopa, broj hromozoma određen je standardnim kariološkim tehnikama, veličina genoma procenjena je pomoću protočne citometrije, a genetički diverzitet primenom molekularne AFLP tehnike... Family Gesneriaceae comprises plant species mostly distributed in the tropics and subtropics of both the Old and New Worlds. Only a small number of species inhabits temperate regions. Among them, there are the only 5 species of this family in Europe: Ramonda myconi, endemic of the Iberian Peninusla, as well as R. nathaliae, R. serbica, Haberlea rhodopensis i Jankaea heldreichii, four endemic species of the Balkan Peninsula. All five species are Tertiary relicts, remnants from the times when the climate was much warmer and more humid. During the Ice Age, they have found shelter in canyons and gorges where can be often found today as well. These „living fossils“ are poikilohydric, „resurrection plants“ what helps them survive the inhospitable environmental conditions. Balkan species of the genus Ramonda are today characterized by disjunct distribution. Ramonda nathaliae is restricted to Macedonia, N Greece, slopes of Mt. Šara in Kosovo and few localities in SE Serbia. The largest part of the R. serbica range is situated in Albania, but is also present in NW Greece, W Macedonia, SW and NE Montenegro, SW, SE and NE Serbia and NE Bulgaria. The ranges of two species cooccur only in two localities in SE Serbia, Oblik and Radovanski Kamen, establishing sympatric populations. Both species prefer limestone rocks, but R. nathaliae can also be found on serpentine, schist and granite. This species is often found in more open habitats and in higher altitudes why it is considered as more resistant and tolerant than R. serbica. The aims of this study are: to investigate morphology of both pollen and seeds of three Ramonda species; to estimate pollen viability and germination capacity of their seeds; to determine chromosome numbers and genome size of three species; to explore if there are hybrids in sympatric populations; to look into genetic diversity and phylogeography of R. nathaliae and R. serbica. Pollen grains and seeds were examined by light and scanning electron microscopy, chromosome number by standard karyological techniques, genome size was estimated by flow cytometry and genetic diversity by molecular AFLP method... Univerzitet u Beogradu Biološki fakultet Stevanović, Vladimir, 1947- Siljak-Yakovlev, Sonja Stevanović, Branka, 1944- Niketić, Marjan, 1961- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=97 https://fedorabg.bg.ac.rs/fedora/get/o:3594/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/42098447 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:99 2013-10-01T00:00:00Z 1

Uticaj životne dobi, estrogenskog statusa i karotidne ateroskleroze na protok krvi kroz zubnu pulpu The influence of age, estrogen status and carotid atherosclerosis on dental pulp blood flow : doctoral dissertation Dželetović, Bojan D., 1983- protok krvi u zubnoj pulpi, starenje, estrogen, karotidna ateroskleroza, spektralna Vejvlet analiza dental pulp blood flow, ageing, estrogen, carotid atherosclerosis, spectral analysis, wavelet analysis Datum odbrane: 20.11.2012. Zubna pulpa predstavlja mikrocirkulatorni sistem koji zbog svoje lokalizacije unutar čvrstih dentinskih zidova ima posebne karakteristike. Glavni dovodni krvni sudovi za zubnu pulpu, kao i druge organe i tkiva orofacijalne regije, su zajednička karotidna arterija (ZKA) i spoljašnja karotidna arterija (SKA). Karotidne arterije, kao i mikrocirkulacija zubne pulpe starenjem podležu različitim strukturnim i funkcionalnim promenama. Pokazano je da fiziološke promene nivoa estrogena u plazmi tokom menstrualnog ciklusa, kao i u menopauzi, značajno utiču na protok krvi u mikrocirkulatornim sistemima mozga i kože. U patološkim uslovima, u prisustvu ateroskleroze karotidnih arterija, postoje značajne promene u protoku krvi u tkivima koja one ishranjuju. Imajući sve ovo u vidu postavljena je hipoteza da životna dob, estrogenski status i ateroskleroza karotidnih arterija značajno utiču na protok krvi u zubnoj pulpi. Ciljevi ovog istraživanja bili su: 1. Odrediti protok krvi kroz krvne sudove zubne pulpe i protok kroz ZKA i SKA kao i debljinu intimo-medijalnog kompleksa (IMK) pomenutih arterija kod zdravih osoba, oba pola, u dve starosne grupe, od 20-25 i od 50- 60 godina (opšta populacija); 2. Ispitati zavisnost protoka krvi u zubnoj pulpi, protoka kroz ZKA i SKA kao i debljine IMK pomenutih arterija u odnosu na životnu dob kod opšte populacije; 3. Ispitati korelaciju između protoka krvi kroz krvne sudove zubne pulpe i protoka kroz ZKA i SKA i debljine IMK pomenutih arterija kod opšte populacije; 4. Odrediti protok krvi kroz krvne sudove zubne pulpe i nivo estrogena kod zdravih žena starosti od 20-25 godina u toku redovnog menstrualnog ciklusa (koji traje 28 dana), u fazi kada je visok estrogen (od 10. do 13. dana) i u fazi niskog estrogena (od 26. do 5. dana), kao i kod žena u menopauzi; 5. Ispitati korelaciju između protoka krvi u krvnim sudovima zubne pulpe i estrogenskog statusa žena sa redovnim menstrualnim ciklusom i žena u menopauzi Dental pulp represents a microcirculatory sistem which due to localization within dentinal walls has specific characteristics. Major feeding blood vesels of dental pulp, as well as orofacial region, are common carotid artery (CCA) and external carotid artery (ECA). Carotid arteries, like dental pulp microcirculation, undergo different structural and functional age-related changes. It has been shown that physiological changes in plasma estrogen levels during the menstrual cycle, and postmenopause, significantly affect blood flow in the microcirculatory system of the brain and skin. In pathological conditions, in presence of carotid atherosclerosis, there are significant changes in blood flow in tissues they supply. Having all this in mind, it was hypothesized that age, estrogen status and carotid atherosclerosis significantly affect blood flow in the dental pulp. The aims of this study were to: 1. Determine dental pulp blood flow and blood flow through the CCA and ECA and intima-media thickness (IMT) of these arteries in healthy adults of both sexes in two age groups of 20-25 and 50-60 years (general population); 2. Examine the dependence of dental pulp blood flow, the flow through the CCA and ECA, and IMT of these arteries in relation to age in the general population; 3. Examine the correlation between dental pulp blood flow and flow through the CCA and ECA and IMT of these arteries in the general population; 4. Determine dental pulp blood flow and estrogen levels in healthy women aged 20-25 years during the regular menstrual cycle (which is 28 days), at a phase when estrogen is high (from 10 to 13 days) and a phase when estrogen is low (from 26 to 5 days), and in postmenopausal women; 5. Examine the correlation between dental pulp blood flow and estrogen levels in women with regular menstrual cycle and postmenopausal women... Univerzitet u Beogradu Stomatološki fakultet Stojić, Dragica, 1952- Kršljak, Elena, 1957- Lukić, Aleksandra, 1946- Grga, Đurica, 1956- Japundžić-Žigon, Nina, 1963- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=99 https://fedorabg.bg.ac.rs/fedora/get/o:3774/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/42651151 sr Autorstvo-Nekomercijalno 3.0 Srbija (CC BY-NC 3.0)

oai:eteze.bg.ac.rs:103 2013-09-25T00:00:00Z 1

Проучавање паразитских гљива на дивљој трешњи (Prunus avium L.) са посебним освртом на биоекологију Daedaleopsis confragosa (Bolt.: Fr.) J. Schroet. Investigation of parasitic funghi on wild cherry (Prunus avium L.) with special accent on bioecology of Daedaleopsis confragosa (Bilt.: Fr.) J. Schroet. : doctoral dissertation Marković, Miroslav P. 1961- Daedaleopsis confragosa, идентификација, Србија, Европа, PCR Daedaleopsis confragosa, identification, Serbia, Europe, PCR Datum odbrane: 24.11.2012. Род Prunus L. обухвата око 200, већином листопадних, а ређе зимзелених дрвенастих врста, које су природно распрострањене у северној хемисфери. Дивља трешња (Prunus avium L.) је један од значајнијих представника овог рода - родоначелник је великог броја најзначајнијих сорти трешања које се данас гаје широм света. Најчешће се јавља као примешана врста, појединачно или, врло ретко, у већим групама. Са еколошког гледишта врло је значајна због своје еколошке прилагодљивости с обзиром да се јавља од низијских шума уз речне токове до подручја високо планинске букве, на граници шумске вегетације. Према својим биолошким својствима прираста и приноса, дивља трешња се сврстава у групу брзорастућих врста, са опходњом од 40-60 година. Погодна је за подизање дрвореда и пољезаштитиних појасева јер је декоративна, медоносна, лековита, плодови су јој јестиви, а уз све то даје и вредну дрвну масу. Истраживања оболења на дивљој трешњи у Србији су врло оскудна. Готово да нема радова у нашој стручној литератури посвећених болестима дивље трешње. Saccardo, P. A. (1898) у свом капиталном делу на дивљој трешњи у целом свету наводи 33 врсте гљива. Треба навести и радове Viennot, G. B. (1949) који на дивљој трешњи детаљно описује 14 врста гљива. Ellis, M., Ellis P. (1985) на роду Prunus бележи 37 врста гљива од чега на дивљој трешњи 4. Dennis, R. W. G. (1978) на Prunus врстама у Енглеској наводи 14 гљива, од чега на дивљој трешњи наводи две. Peace, T. R. (1962) у књизи о болестима дрвећа и жбуња у Британији на Prunus врстама наводи 23 врста гљиве а на дивљој трешњи 5. Ogawa, M. J. et al. (1995) на Prunus врстама у Америци бележе 35 врста гљива, углавном као изазиваче оболења у воћњацима док на дивљој трешњи наводе 3. Sutton, C. B. (1980) на роду Prunus бележи 13 врста гљиве од чега посебно на дивљој трешњи 2 врсте. Током ових истраживања, Марковић, М. (2012) је на дивљој трешњи у Србији забележио 47 врста паразитских и сапрофитских гљива, од чега је по први пут на дивљој трешњи у Србији забележено 31 врста. Од 31 новозабележене врсте гљива, 5 гљива никада нису констатоване у Србији, а 26 је забележено, али на другим домаћинима. На свим ликалитетима истраживања гљива Daedaleopsis confragosa је често налажена на сувим гранама и лежећем дрвном материјалу што потврђује мишљење већине аутора да се ради о сапрофиту. Међутим, ова гљива је током истраћивања у Србији, врло често налажена на живим стаблима (и до висине од 15 m) и гранама дивље трешње, што нас је навело да овој гљиви посветимо посебну пажњу... The genus Prunus L. includes roughly 200 species, mostly broadleaf and rarely coniferous trees, naturally distributed over the Northern Hemisphere. Wild sweet cherry (Prunus avium L.) is one of the important representatives of this genus, from which a great number of the most important cherry varieties worldwide are derived. It occurs most often in a mixture of species, individually, or very rarely in larger groups. From an ecological point of view, it is very significant due to its environmental adaptability as it ranges from the lowland forest along the river flow to the area of high mountain beech at the edge of the forest vegetation. According to its properties of growth and yield, the wild sweet cherry belongs to the group of fast growing trees, with rotation period as long as 60-40 years. It is suitable for formation of tree alleys and protection belts due to its decorative appearance, medical properties, edible fruits, and on top of all that it gives a valuable wood mass. Researches done on wild sweet cherry diseases in Serbia are very scarce. There is hardly any science-based paper devoted to wild sweet cherry diseases. Saccardo, P. A. (1898) in his capital work on wild sweet cherry mentioned some 33 fungal species worldwide. The works of the following authors should also be mentioned: Viennot, G. B. (1949), who described 14 fungal species on wild sweet cherry; Ellis, M., Ellis P. (1985), who described 37 fungal species on Prunus, from which four on wild sweet cherry; Dennis, R. W. G. (1978) described 14 fungal species on Prunus in England, from which two on wild sweet cherry; Peace, T. R. (1962) in his book on diseases of trees and shrubs in Britain mentioned 23 fungal species on Prunus species, and five on wild sweet cherry; Ogawa, M. J. et al. (1995) observed 35 fungal species as possible causes of diseases on Prunus in orchards in America, while only three on wild sweet cherry; Sutton, C. B. (1980) observed 13 fungal species on Prunus, from which two on wild sweet cherry. During these studies, Markovic, M (2012) observed 47 parasitic and saprophytic fungi on wild sweet cherry in Serbia, from which 31 species were observed on wild sweet cherry for the first time. Of the 31 newly observed fungal species, five fungi were never recorded in Serbia, and 26 were observed but on different hosts. At all studied localities the fungus Daedaleopsis confragosa was often observed on dry branches and dead woody material, which confirmed the opinion of the majority of authors that it was the saprophyte. However, during studies in Serbia this fungus was often found on living trees (up to 15 m of height) and branches of wild sweet cherry, which made us pay special attention to this fungus... Univerzitet u Beogradu Šumarski fakultet Karadžić, Dragan, 1950- Karadžić, Dragan, 1950- Keča, Nenad, 1975- Galović, Vladislava Golubović-Ćurguz, Vesna, 1958- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=103 https://fedorabg.bg.ac.rs/fedora/get/o:3997/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/512531612 sr Autorstvo-Nekomercijalno 3.0 Srbija (CC BY-NC 3.0)

oai:eteze.bg.ac.rs:104 2013-09-25T00:00:00Z 1

Prilоg rаzvојu mеtоdоlоgiје zа izbоr trаsа zа krеtаnjе vоzilа kоја trаnspоrtuјu оpаsnu rоbu sа аspеktа uprаvlјаnjа rizikоm Development of methodology for the selection of routes for the movement of vehicles transporting dangerous goods in terms of risk management Milovanović, Branko M. 1979- оpаsnа rоbа, uprаvlјаnjе rizikоm, izbоr trаsа, incidеntnа situаciја, individuаlni rizik, društvеni rizik, vоzilа dangerous goods, risk management, selection of routes, incident situation, individual risk, societal risk, vehicles.Opasne materije Datum odbrane: 06.07.2012. U cilјu bеzbеdnоg izvršеnjа trаnspоrtnоg prоcеsа оpаsnе rоbе nеоphоdnо је uprаvlјаti rizikоm, kојi prеdstаvlја vеоmа slоžеn prоcеs, а јеdаn оd kоrаkа u оkviru оvоg prоcеsа је izbоr trаsа zа krеtаnjе vоzilа kоја trаnspоrtuјu оpаsnu rоbu. Izvršiti izbоr trаsа zа krеtаnjе vоzilа kоја trаnspоrtuјu оpаsnu rоbu а pri tоmе nе izvršiti kvаntifikаciјu nivоа rizikа u оkviru svаkе trаsе, dоvеlо bi dо mоgućnоsti pоgrеšnоg izbоrа а sаmim tim i vеlikih pоtеnciјаnih pоslеdicа kоје mоžе dа izаzоvе оpаsnа rоbа kоја sе trаnspоrtuје. Kаkо bi sе izvršiо аdеkvаtаn izbоr trаsа sа аspеktа uprаvlјаnjа rizikоm, u оkviru rаdа dаt је prikаz prоcеsа uprаvlјаnjа rizikоm u trаnspоrtu оpаsnе rоbе, оdnоsnо prikаz fаzа iz kојih sе prоcеs uprаvlјаnjа rizikоm sаstојi i dаt је dеtаlјаn оpis svаkе fаzе pоsеbnо. Оdrеđеnо је i mеstо i znаčај izbоrа trаsа zа krеtаnjе vоzilа kоја trаnspоrtuјu оpаsnu rоbu, kоја prеdstаvlја јеdnu оd pоčеtnih аktivnоsti u оkviru izrаdе аnаlizе оpаsnоsti оd nаstаnkа incidеntnе situаciје, оdnоsnо prvе fаzе pоmеnutоg prоcеsа. Pоsеbnа pаžnjа је pоsvеćеnа оdrеđivаnju nivоа društvеnоg i individuаlnоg rizikа zbоg vеlikе znаčајnоsti оvih vrstа rizikа pri izbоru trаsа zа krеtаnjе vоzilа kоја trаnspоrtuјu оpаsnu rоbu sа аspеktа uprаvlјаnjа rizikоm. U trеćеm pоglаvlјu rаdа dаt је prikаz nајvаžniјih mеtоdоlоgiја iz litеrаturе оd strаnе inоstrаnih аutоrа kоје sе оdnоsе nа izbоr trаsа zа krеtаnjе vоzilа kоја trаnspоrtuјu оpаsnu rоbu nа оsnоvu nivоа individuаlnоg i društvеnоg rizikа i nа оsnоvu аpsоlutnоg i rеlаtivnоg rizikа. Zа prеthоdnо dvе nаvеdеnе grupе mеtоdоlоgiја dаt је njihоv krаtаk prikаz, kоrаci iz kојih sе оnе sаstоје, prеdnоsti i nеdоstаci, kао i pоdručје njihоvе primеnе. U оkviru čеtvrtоg pоglаvlја rаdа dаt је blоk diјаgrаm nа kоmе su prikаzаni kоrаci u оkviru mеtоdоlоgiје zа izbоr trаsа zа krеtаnjе vоzilа kоја trаnspоrtuјu оpаsnu rоbu sа аspеktа uprаvlјаnjа rizikоm. Меtоdоlоgiја kоја је prеzеntirаnа u čеtvrtоm pоglаvlјu rаdа оbјеdinjuје svе mоgućе еlеmеntе kојi utiču ili оnе kојi mоgu uticаti nа izbоr trаsе zа krеtаnjе vоzilа kоја trаnspоrtuјu оpаsnu rоbu nа оsnоvu vеličinе аpsоlutnоg rizikа. Меtоdоlоgiја sе sаstојi iz 11 kоrаkа i zаsnivа sе nа izbоru trаsа zа trаnspоrt оpаsnе rоbе nа оsnоvu аpsоlutnоg rizikа, оdnоsnо rizikа kојi sе mоžе kvаntifikоvаti. Оnа оbјеdinjuје svе fаzе u оkviru prvе fаzе u оkviru Меtоdоlоgiје uprаvlјаnjа rizikоm оd nаstаnkа incidеntnе situаciје. Idеntifikаciја оpаsnоsti i vеličinа pоslеdicа оd nаstаnkа incidеntnе situаciје su оbuhvаćеnе u оkviru prvih pеt kоrаkа mеtоdоlоgiје, dоk је prоcеnа rizikа kао zаvršnа fаzа u оkviru аnаlizе оpаsnоsti оd nаstаnkа incidеntnе situаciје sprоvеdеnа krоz sеdmi, оsmi, dеvеti i dеsеti kоrаk. Kао јеdаn оd kоrаkа u оkviru mеtоdоlоgiје је i primеnа mоdеlа zаsnоvаnоg nа utvrđivаnju аpsоlutnоg rizikа i dеfinisаnjа prihvаtlјivоg nivоа rizikа оdrеđеnе dеоnicе putа, оdnоsnо dеlа trаsе. U cilјu utvrđivаnjа nivоа rizikа u оkviru mеtоdоlоgiје dеfinisаni su pаrаmеtri kојi utiču nа vеličinu vеrоvаtnоćе nаstаnkа incidеntnе situаciје i pаrаmеtri kојi utiču nа vеličinu pоslеdicа i njihоvе vrеdnоsti su pоvеzаnе sа vеličinоm rizikа, dоk је zа svаki pаrаmеtаr utvrđеn njеgоv tеžinski fаktоr nа оsnоvu sprоvеdеnе аnkеtе еkspеrаtа. U оkviru pоslеdnjеg pоglаvlја dаt је prikаz primеnе unаprеđеnе mеtоdоlоgiје nа mrеžu sаоbrаćајnicа nа tеritоriјi grаdа Bеоgrаdа sа cilјеm izbоrа trаsа zа krеtаnjе vоzilа kоја trаnspоrtuјu оpаsnu rоbu sа аspеktа uprаvlјаnjа rizikоm. Kаkо bi sе sprоvеlа cеlоkupnа mеtоdоlоgiја, sprоvеdеnа su оpsеžnа istrаživаnjа kаrаktеristikа trаnspоrtnih zаhtеvа nаftе i nаftnih dеrivаtа nа tоtаlnоm uzоrku zа pоdručје Rеpublikе Srbiје, dеfinisаni tеžinski fаkоri zа svаki pаrаmеtаr i utvrđеnе njihоvе vrеdnоsti zа svаku оd izаbrаnih dеоnicа, оdnоsnо zа svаku dеоnicu pоsеbnо је fоrmirаnа mаtricа rizikа nа оsnоvu kоје је dоnеtа оdlukа dа li је оdrеđеnа dеоnicа u оkviru trаsе pоdоbnа zа trаnspоrt оpаsnе rоbе ili nе sа аspеktа dоzvоlјеnоg nivоа rizikа. Nа оsnоvu sprоvеdеnih svih kоrаkа u оkviru mеtоdоlоgiје, nа krајu rаdа dаt је prikаz trаsа zа krеtаnjе vоzilа kоја trаnspоrtuјu оpаsnu rоbu nа tеritоriјi grаdа Bеоgrаdа nа оsnоvu upоrеđеnjа vеličinе rizikа nа tој dеоnici sа dоzvоlјеnim nivооm rizikа. In order to secure the execution process of the transport of dangerous goods it is necessary to manage risk, which is a very complex process, and one of the steps in this process is the selection of routes for the movement of vehicles transporting dangerous goods. Make a selection of routes for the movement of vehicles transporting dangerous goods while not perform quantification of risk levels within each route would lead to the possibility of a wrong choice and thus of potential major consequences that can lead to dangerous goods being transported. In order to execute an appropriate choice of route in terms of risk management within the article gives an overview of risk management in the transport of dangerous goods, or display the phase from which the risk management process and includes a detailed description of each stage separately. Is determined by the place and importance of the route for the movement of vehicles transporting dangerous goods, which is one of the initial activity within the development of hazard analysis of the occurrence of the incident or the first stage of the process. Special attention is paid to determining the level of social and individual risk because of the significance of these kinds of risks in choosing the route for the movement of vehicles transporting dangerous goods in terms of risk management. In the third section of the paper presents the most important methodologies in the literature by foreign authors concerning the choice of route for the movement of vehicles transporting dangerous goods by the level of individual and social risk on the basis of absolute and relative risk. For the two previously mentioned groups methodology is given in their brief statement, the steps from which they are made, the advantages and disadvantages, as well as their application area. In the fourth chapter of the paper is a block diagram which shows the steps in the methodology for choosing the route for the movement of vehicles transporting dangerous goods in terms of risk management. The methodology presented ucetvrtom of chapter combines all the elements that can affect or which may affect the choice of route for the movement of vehicles transporting dangerous goods based on the size of absolute risk. The methodology consists of 11 steps and is based on choosing the route for the transport of dangerous goods on the basis of absolute risk, that risk can be quantified. It combines all the stages in the first phase of the Risk Management Methodology occurrence of the incident. The identification of hazards and consequences of occurrence of the size of the incident are included in the first five steps of the methodology, while the risk assessment as the final stage in the analysis of the risk of occurrence of the incident conducted by the seventh, eighth, ninth and tenth step. As one of the steps in the methodology and the use of model-based determination of absolute risk and defining acceptable risk levels specific sections of the road or part of the route. In order to determine the level of risk according to the methodology defined by the parameters that influence the size of the probability of occurrence of the incident and the parameters that influence the size of the result and the value associated with the size of risk, and for each parameter determined by its weighting factor based on the survey of experts. In the last chapter presents the application of improved methodologies to network traffic in the city of Belgrade with the objective of the route for the movement of vehicles transporting dangerous goods in terms of risk management. In order to implement the entire methodology, conducted the comprehensive study of the characteristics of transportation requires oil and petroleum products in the total sample for the Republic of Serbia, the growth factor defined by weight for each parameter and their values are determined for each of the selected section, and for each section separately formed matrix risk on the basis that the decision is made whether a particular section of the route suitable for the transport of dangerous goods or not in terms of allowable levels of risk. Based on performed all the steps in the methodology, at the end of the paper presents a route for movement of vehicles transporting dangerous goods in the territory of Belgrade on the basis of comparisons of the size of the risk in this section of the allowable level of risk. Univerzitet u Beogradu Saobraćajni fakultet Jovanović, Vojkan D., 1948- Filipović, Snežana M. 1947- Gladović, Pavle K., 1951- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=104 https://fedorabg.bg.ac.rs/fedora/get/o:5097/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/512305834 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:146 2013-11-13T00:00:00Z 1

Dramske obrade mita o Filoktetu u zapadnoevropskoj i srpskoj književnosti Dramatic versions of Philoctetes myth in the Western European and Serbian literature Stolić, Dragana N., 1969- mit, Filоktеt, Оdisеј, Sоfоklе, Аndrе Žid Vеlimir Lukić, Hајnеr Мilеr, Šејmаs Hini myth, Philoctetes, Odysseus, Sophocles, André Gide, Velimir Lukić, Heiner Miller, Seamus Heaney Datum odbrane: 08.05.2013. Rаd pоd nаzivоm “Drаmskе оbrаdе mitа о Filоktеtu u zаpаdnоеvrоpskој i srpskој knjižеvnоsti” pоlаzi оd nајstаriјih pisаnih izvоrа u kојimа sе pоminjе trојаnski јunаk Filоktеt, prеkо prvih drаmskih оbrаdа mitа u dеlimа Еshilа, Еuripidа i Sоfоklа, dо dvаdеsеtоvеkоvnih drаmа kоје su nа nоvi nаčin pristupilе оvој tеmi, mеnjајući је u sklаdu sа nоvim istоriјskim iskustvоm. Nајvišе pаžnjе је pоsvеćеnо drаmаmа Аndrеа Židа (“Filоktеt”, 1898), Hајnеrа Мilеrа (“Filоktеt”, 1968), Vеlimirа Lukićа (“I smrt dоlаzi nа Lеmnо”, 1970) i Šејmаsа Hiniја (“Iscеlјеnjе kоd Тrоје”, 1990). Оsim оvоg glаvnоg kоrpusа, prеdmеt prоučаvаnjа su bilа i drugа, mаnjе pоznаtа drаmskа dеlа nаstаlа nа tlu Еvrоpе, kао štо је “Filоktеt” Žаn-Bаtistа Šаtоbrеnа iz 1756. gоdinе. Rаdi pоtpunоg uvidа u rаzvој i prisustvо mitа оd аntikе krоz pоtоnjе vеkоvе, bilо је nеоphоdnо pоmеnuti i dеlа kоја nе pripаdајu sаmо drаmskој knjižеvnоsti, pа ni knjižеvnоsti uоpštе (Fеnеlоnоv rоmаn “Теlеmаh” ili dеlа likоvnе umеtnоsti). Nа krајu, krаtkо је prоučеnо i prisustvо mitа u vаnеvrоpskim knjižеvnоstimа, u drаmi (Оskаr Маndеl) ili rоmаnu (Rоbеrt Silvеrbеrg). Pоrеd tеžnjе dа sе krоz štо iscrpniјi prеglеd prikаžе kоlikо је оvај mit оbrаđivаn u knjižеvnоsti, prе svеgа drаmskој, оd аntičkе trаgеdiје dо dаnаšnjеg tеаtrа, u rаdu sе оtvаrа i pitаnjе zаštо је оn pоstао prеdmеt intеrеsоvаnjа mоdеrnih аutоrа. Pоlаzеći оd prеtpоstаvkе dа је nајznаčајniјu ulоgu u tоm prоcеsu imаlа Sоfоklоvа drаmа, kоја је zа rаzliku оd Еshilоvе u Еuripidоvе sаčuvаnа, pristupilо sе njеnој dеtаlјnој аnаlizi kаkо bi sе dоkаzаlо dа su uprаvо Sоfоklоvа drаmskа rеšеnjа, nаčin pоstаvlјаnjа zаplеtа i čitаvе drаmskе strukurе prоuzrоkоvаli dа drаmа budе intrigаntnа i mnоgо nаkоn vrеmеnа u kојеm је nаstаlа i u sаsvim drugаčiјim kulturnim i istоriјskim kоntеkstimа. Svi budući аutоri su, stvаrајući svоја dеlа, pоlаzili оd Sоfоklоvоg, uglеdајući sе nа njеgа i оdrеđuјući sе u оdnоsu nа tоg аntičkоg Filоktеtа. Sоfоklоvа drаmа је јеdаn оd klјučnih kоnstituеnаtа оnоgа štо dаnаs zоvеmо mitоm о Filоktеtu, аli i prvа sаčuvаnа cеlоvitа drаmskа оbrаdа оvоg mitа. Оnа је istоvrеmеnо pоstаlа i nеzаоbilаznа smеrnicа drugim аutоrimа, јеr је stvоrilа strukturu zаsnоvаnu nа nеrеšivоm sukоbu аntаgоnistа – Filоktеtа i Оdisеја, čiјi su pоstupci višеstukо mоtivisаni i čiје su ulоgе krајnjе аmbilаvеntnе. Sоfоklоvа drаmа u kојој sе pојаvlјuјu sаmо muški likоvi pоkrеnulа је niz pitаnjа mеđu kојimа је prе svеgа оdnоs pојеdincа prеmа društvu ili zајеdnici, stаvlјајući nаglаsаk nа čоvеkа kао nа pоlitičku živоtinju, štо su аutоri, nаrоčitо dvаdеsеtоvеkоvni, prеpоznаli kао dео svоg iskustvа. Paper "Dramatic Versions of Philoctetes Myth in the Western European and Serbian Literature" begins from the oldest written sources in which the Trojan hero Philoctetes is mentioned, investigates first known dramatic versions of that myth in the work of Aeschylus, Euripides and Sophocles, and continues till 20th century drama which had new approach to this theme, changing it according to new historical experiences. This part is mainly dedicated to drama of André Gide ("Philoctetes", 1898), Heiner Miller("Philoktet", 1968), Velimir Lukić ("And death comes to Lemnos", 1970) and Seamus Heaney ("The Cure at Troy", 1990). Beside this main subject, we have also researched other, less known dramatic work which emerged in Europe, as "Philoctetes" of Jean-Baptiste de Chateaubrun from 1756. For the purpose of complete insight into presence of myth from antiquity to following centuries it was necessary to mention the works of art, like novels (Fénelone’s "Télémaque") or paintings. Finally, it is shortly analyzed the presence of myth in literature outside of Europe, in drama (Oscar Mandel) or novel (Robert Silverberg). Beside the tendency to offer most exhaustive overview and to show the presence of this myth in drama from antiquity to present day, paper discusses also the question of reasons why it became the object of interest to modern authors. Having the presumption that the most significant role in this process had drama of Sophocles, which is extant, differently from versions of Aeschylus or Euripides, it is analyzed in detail. The purpose of such approach is to make obvious that Sophocles’ solutions as such, his version of plot and dramatic structure made this story attractive long after its genesis and in totally different cultural and historical contexts. The starting point for all future authors was drama of Sophocles which they followed as an example and to which they determined their own work. Drama of Sophocles makes one of the key components of what we call “myth of Philoctetes”, but at the same time this is first complete dramatic version of that myth. By pointing out the unsolved antagonism between Philoctetes and Odysseus, whose actions has complex motivation and whose roles are highly ambivalent, drama became an inevitable guideline to other authors. Sophocles’ drama, with all male characters initiated many questions such as the position of individual among the societyor community, and emphasized the man as a “political animal”, which was something that authors from 20th century recognized as a part of their own experience. Univerzitet u Beogradu Filološki fakultet Popov, Jovan, 1962- Maričić, Gordan, 1964- Bečanović Nikolić, Zorica, 1963- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=146 https://fedorabg.bg.ac.rs/fedora/get/o:5368/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/43926543 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:147 2013-09-25T00:00:00Z 1

Аnаlizа mеtоdа zа zаštitu vеtrоеlеktrаnа оd dirеktnоg аtmоsfеrskоg prаžnjеnjа Analysis of the methods for wind turbine protection against direct atmospheric discharges Radičević, Branko M. 1970- atmоsfеrskо prаžnjеnjе, vеtrоеlеktrаnа, grоmоbrаnskа zаštitа, mоdеl, еlisa, rоtаciја, prеskоčni nаpоn atmospheric discharge, wind turbine, lightning protection, model, blade, rotation, flashover voltage Datum odbrane: 22.05.2012. Теmа dоktоrskе disеrtаciје је vеоmа аktuеlnа zbоg intеnzivnоg širеnjа primеnе vеtrоеlеktrаnа širоm svеtа sа јеdnе strаnе, а sа drugе strаnе zbоg njihоvе оsеtlјivоsti nа аtmоsfеrskе udаrе i tеških pоslеdicа kоје pri tоmе nаstајu. Vеtrоturbinе su visоkе nеstаndаrdnе kоnstrukciје sа rоtirајućim еlеmеntimа, kоје sе оbičnо instаlirајu nа lоkаciјаmа nа kојimа је kеrаunički nivо vеоmа visоk i lоši uslоvi uzеmlјеnjа, i kао distribuirаni izvоri еlеktričnе еnеrgiје imајu pоvеćаn rizik оd udаrа grоmа. Nајistаknutiјi dеlоvi vеtrоturbinа, kао štо su dugаčkе еlisе i gоndоlа, tipičnо su nаprаvlјеni оd kоmpоzitnih mаtеriјаlа, kојi nе mоgu uspеšnо dа izdržе dirеktnе udаrе grоmа sа struјаmа intеnzitеtа dо 200 kA, niti prоticаnjе struја prаžnjеnjа pо njihоvој pоvršini, pri čеmu znаčајаn dео оvе struје, prilikоm sprоvоđеnjа u zеmlјu, imа putаnju prеkо ili u blizini prаktičnо svih vitаlnih kоmpоnеnti vеtrоturbinе. Kоntinuirаn rаzvој zаštitnih sistеmа vеtrоеlеktrаnа оd аtmоsfеrskih prаžnjеnjа imа izuzеtаn znаčај kаkо bi sе smаnjilе štеtnе pоslеdicе zbоg mеhаničkih оštеćеnjа еlisа, kvаrоvа nа еlеktričnој i еlеktrоnskој оprеmi i ispаdа vеtrоеlеktrаnа iz pоgоnа. Оriginаlnа tеоriјskа rаzmаtrаnjа, primеnа sоftvеrskо-numеričkih pоstupаkа, i vеоmа izаzоvnо i finаnsiјski zаhtеvnо еkspеrimеntаlnо ispitivаnjе, оmоgućili su dа sе u dоktоrskој tеzi nа kvаlitеtаn nаčin izvrši аnаlizа mеtоdа zа zаštitu vеtrоеlеktrаnа оd dirеktnоg аtmоsfеrskоg prаžnjеnjа i dоbiјu znаčајni dоprinоsi. Istrаživаnjа kоја su sprоvеdеnа u tоku izrаdе dоktоrskе disеrtаciје su dоstа slоžеnа, zbоg prirоdе pојаvа kоје sе ispituјu i nеstаndаrdnih nаčinа ispitivаnjа, а istоvrеmеnо i multidisciplinаrnа, јеr оbuhvаtајu dоbrо pоznаvаnjе slеdеćih оblаsti: tеhnikа visоkоg nаpоnа, vеtrоеnеrgеtikа, fizikа аtmоsfеrskih prаžnjеnjа i grоmоbrаnskа zаštitа. U prvоm dеlu disеrtаciје оbјаšnjеn је svе vеći znаčај kоје vеtrоеlеktrаnе imајu u sаvrеmеnоm dеcеntrаlizоvаnоm ЕЕS-u, dаt је prеglеd аktuеlnоg stаnjа i stаndаrdа u vеzi sа аtmоsfеrskim prаžnjеnjimа u vеtrоturbinе i ukаzаnо је nа spеcifičnоsti mеtоdа njihоvе grоmоbrаnskе zаštitе. Prikаzаni su glаvni dеlоvi sаvrеmеnе vеtrоturbinе, kоја је vеоmа kоmplеksаn urеđај, pri čеmu је pоsеbnа pаžnjа pоsvеćеnа аnаlizi kаrаktеristikа i nаčinimа zаštitе kоmpоnеnti krоz kоје prоtičе glаvni dео struје prаžnjеnjа. Rаzmоtrеni su rаzličiti principi zа zаštitu kоmpоzitnih mаtеriјаlа оd аtmоsfеrskоg prаžnjеnjа i оbјаšnjеnо је kоје vrstе kоmpоzitа i u kојој mеri mоgu dа sе kоristе zа izrаdu еlisа vеtrоturbinа. Dаt је prеglеd rеlеvаntnih pаrаmеtаrа i kаrаktеristikа dirеktnih аtmоsfеrskih prаžnjеnjа kоја sе tipičnо dеšаvајu nа vеtrоturbinаmа kоје su u pоgоnu. U tеzi је rаzmоtrеn оpšti princip grоmоbrаnskе zаštitе vеtrоеlеktrаnа, zаsnоvаn nа оdrеđivаnju pоtrеbnоg nivоа zаštitе grоmоbrаnskе instаlаciје. Аnаlizirаnа su čеtiri nivоа zаštitе, pri čеmu su zа svаki оd njih dеfinisаni kritеriјumi kоје trеbа dа zаdоvоlјi svаki оd еlеmеnаtа grоmоbrаnskоg zаštitnоg sistеmа. Ispitivаnjе оvih kritеriјumа trеbа dа оbеzbеdi dа vеrоvаtnоćа еfikаsnоg dеlоvаnjа zаštitе budе u оkviru unаprеd dеfinisаnih grаnicа, kоје su kаrаktеrističnе zа svаki оd nivоа zаštitе. Prеdlоžеni su pоstupci zа izrаčunаvаnjе rаčunskе еfikаsnоsti grоmоbrаnskе instаlаciје vеtrоеlеktrаnе i udаrnоg rаstојаnjа nа оsnоvu kојih sе јеdinstvеnо оdrеđuје nivо zаštitе štićеnе vеtrоеlеktrаnе... The subject of this PhD Thesis is a very current subject due to intensive progress in applying wind turbines around the world on one hand, and on the other hand due to their sensitivity to atmospheric discharges and serious consequences that can arise. Wind turbines are tall and nonstandard constructions with rotating elements, usually installed in locations at which the keraunic level is very high and grounding conditions are bad, and as distributed sources of electrical energy they are more prone to lightning stikes. The most prominent parts of the wind turbines, e.g. long blades and nacelle are typically made of composite materials, which cannot successfully withstand direct lightning strikes with currents up to 200 kA, neither current disharge flow on their surface, during which a significant part of this current at grounding has a path over or in vicinity of practically all vital components of the wind turbine. Continuous development of protective wind turbine systems for atmospheric discharges has a remarkable significance in order to reduce negative consequences of mechanical damages of blades, failure of electrical and electronic equipment and outage rate. Original theoretical discussions, applying software numerical procedures and very chalenging and financially demanding experimental testing enabled a high quality analysis to be preformed in the PhD Thesis regarding direct atmospheric discharges and to significally contribute to the subject. The research conducted during work on this PhD Thesis are rather complex due to nature of the events that are the subject of the research and non-standard ways of testing and at the same time multidisciplinary because they involve a good knowledge of the following fields: highvoltage technique, wind energy, atmospheric discharge physics and lightning protection. In the first part of this thesis the increasing significance that wind turbines have in contemporary decentralized EES, an overview of actual state and standards with regards to atmospheric discharges into wind turbines, and the specifics of the methods of their lighting protections have been pointed out. The main parts of the modern wind turbine are shown, because the wind turbine is a very complex device, and special attention is paid to the analysis of characteristics and means of protection of components through which the main part of the discharge current flows. Different principles for protection of composite materials from atmospheric discharges are discussed and explanations on which types of composites can be used to construct wind turbine blades and to what extent. An overview is given of the relevant parameters and characteristics of direct atmospheric discharges, which typically happen on wind turbine in service. The general principle of lightning protection of wind turbines is discussed in the thesis, based on determination of the necessary level of protection of electrical installation for lightning protection. Four levels of protection are analyzed, and for each of them criteria are defined which need to be meet by each element of the lightning protection system. The testing of these criteria needs to enable the probability of efficient work of protection is within predefined limits which are characteristic for each level of protection. The proposed procedures for calculating evaluation efficiency of lightning protection installation of wind turbine and striking distance based on which the level of protection of the protected wind turbine is uniquely determined... Univerzitet u Beogradu Elektrotehnički fakultet Savić, Milan S., 1947- Rajaković, Nikola, 1942- Gerić, Ljubomir Stojković, Zlatan, 1960- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=147 https://fedorabg.bg.ac.rs/fedora/get/o:5376/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/40758799 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:151 2013-07-23T00:00:00Z 1

Fluktuirajuća asimetrija kao pokazatelj stabilnosti razvića odabranih biljnih taksona u uslovima nenarušene životne sredine i antropogeno indukovanog stresa : doktorska disertacija Fluctuating asymmetry as an indicator of developmental stability of selected plant taxa in unpolluted environment and under anthropogenically induced stress Barišić-Klisarić, Nataša R., 1973- Robinia pseudoacacia, Iris pumila, Iris germanica, razvojna stabilnost, radijalna asimetrija, fluktuirajuća asimetrija, biomonitoring Robinia pseudoacacia, Iris pumila, Iris germanica, developmental stability, radial asymmetry, fluctuating asymmetry, biomonitoring Datum odbrane: 27.12.2012. Promene u životnoj sredini od industrijske revolucije do danas su bez presedana u istoriji živog sveta i svojim razmerama prete da nadmaše adaptivni potencijal mnogih živih organizama, naročito biljaka, koje kao sesilni organizmi imaju samo ograničene mehanizme za izbegavanje stresa. Razumevanje kako biljke reaguju na ovakve promene, od subcelularnog do nivoa zajednica, je od krucijalnog značaja. U ovom radu smo ispitivali mogućnosti korišćenja analiza fluktuirajuće i radijalne asimetrije kao pokazatelja stabilnosti razvića vegetativnih i reproduktivnih organa kod dve zeljaste monokotile (Iris pumila i Iris germanica) i jedne drvenaste dikotile (Robinia pseudoacacia), u uslovima nenarušene životne sredine i u uslovima antropogeno uzrokovanog stresa (zagađenja u industrijskim i urbanim zonama). Analizirali smo mogućnosti korišćenja ovih analiza kao primarnih indikatora u sredinama sa negativnim antropogenim uticajem, kao i prednosti i mane ovog i nekih drugih metoda detekcije zagađenja. Stabilnost razvića procenjena putem fluktuirajuće i radijalne asimetrije se razlikuje između izučavanih sredina u slučaju sve tri vrste. Kod vrste R. pseudoacacia kao sredina u kojoj je detektovan najveći stepen razvojne nestabilnosti se izdvojio Kostolac (antropogeno degradirana sredina). Kod vrste I. pumila su biljke poreklom iz sredine pod antropogenim uticajem pokazale veću razvojnu nestabilnost kako u slučaju fluktuirajuće asimetrije, tako i u slučaju radijalne asimetrije. Kod vrste I. germanica su detektovane značajne razlike između zagađenja u slučaju indeksa radijalne asimetrije gde su biljke poreklom sa zagađenog staništa pokazale značajno veću razvojnu nestabilnost od biljaka poreklom sa nezagađenog staništa. Kod sve tri vrste je utvrđena značajna interakcija individue i asimetrije osobina, tj. da ekspresija razlika u fluktuirajućoj i radijalnoj asimetriji između ispitivanih osobina zavisi od klona tj. individue. Changes in the environment from the industrial revolution till present are unprecedented in the history of the life on Earth and their magnitude can overpower the adaptive potential of many living organisms, especially plants, that are sessile and have only limited mechanisms for avoiding stress. Understanding how plants respond to these changes, from subcellular to the community level, is crucial. In this study we investigated the possibility of using analysis of fluctuating and radial asymmetry as an indicator of developmental stability of vegetative and reproductive organs in two herbaceous monocots (Iris pumila and Iris germanica) and one wooden dikotile (Robinia pseudoacacia), in unpolluted environment, as well as in environment characterized by anthropogenically induced stress (industrial and urban zones pollution). We have analyzed the possibility of using this analysis as a primary indicator of pollution in areas with negative human impact, and the advantages and disadvantages of these and some other methods of pollution detection. Developmental stability estimated by fluctuating and radial asymmetry differed between the studied habitats for all three species. For R. pseudoacacia plants from Kostolac (polluted environment) had the highest degree of developmental instability. I. pumila plants originated from the environment under the influence of anthropogenic stress showed greater developmental instability in the case of fluctuating asymmetry, as well as radial asymmetry. In I. germanica species we detected significant differences between polluted and unpolluted habitats estimated by radial asymmetry where the plants originated from contaminated habitats showed significantly greater developmental instability. In all three species we detected significant interaction between individuals and trait asymmetries, e.g. expression of the difference in the radial and fluctuating asymmetry between the studied traits depended on the individual (clone). Univerzitet u Beogradu Biološki fakultet Tarasjev, Aleksej Stevanović, Vladimir, 1947- Miljković, Danijela Avramov, Stevan 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=151 https://fedorabg.bg.ac.rs/fedora/get/o:5384/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/43481359 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:153 2013-07-23T00:00:00Z 1

Morfološka i genetička karakterizacija Aphidius colemani kompleksa vrsta (Hymenoptera, Braconidae) Morphological and genetic characterization of Aphidius colemani species complex (Hymenoptera, Braconidae) Shukshuk, Alkasm Hesen, 1972- Aphidius colemani, Aphidius transcaspicus, morfometrija, citohrom oksidaza subjedinica 1, parazitoidi Aphidius colemani, Aphidius transcaspicus, morphometry, COI mtDNA Datum odbrane: 5.2.2012. Aphidius colemani kompleks vrsta je definisan kao grupa vrsta sa pantropsko-suptropskim rasprostranjenjem koja se odlikuje malim brojem brazdi, karakterističnog položaja, na anterolateralnom regionu petiolusa. Predstavlja jednu od 10 grupa vrsta (kompleksa) sa nerešenim taksonomskim statusom u okviru roda Aphidius. Morfološka i genetička karakterizacija Aphidius colemani kompleksa izvršena je primenom morfometrije i analize sekvenci barkoding regiona gena za subjedinicu jedan citohrom oksidaze (COI). Morfometrijskim analizama obuhvaćeno je 250 jedinki A. colemani kompleksa sа prostorа 23 države sa četiri kontinenta. Analizom varijabilnosti morfoloških karaktera pokazano je postojanje značajnih razlika u pogledu njihove informativnosti u pogledu razdavjanja različitih grupa ovog kompleksa. UtvrĎeno je koji su morfološki karakteri dovoljno informativni za razlikovanje taksona unutar ovog kompleksa parazitskih osa. Molekularne analize su obuhvatile 54 jedinke iz 8 država. Analizom sekvenci COI gena i rekonstrukcijom filogenetskih odnosa utvrĎeno je postojanje skrivenog taksona unutar A. colemani kompleksa. Kombinacijom rmorfometrijskih i molekularnih metoda utvrĎeno je da u okviru Aphidius colemani kompleksa vrsta postoje najmanje tri taksona: Aphidius colemani, Aphidius transcaspicus i Aphidius cf. colemani 1 (novi takson). UtvrĎeno je da novotkirvena vrsta naseljava Aziju (Iran) i Južnu Ameriku (Čile). Pokazano je da ne postoji jasna veza izmeĎu genetičke diferencijacije parazitoida ovog kompleksa i njihovih afidnih domaćina, kao ni izmeĎu genetičke diferencijacije i geografskog porekla. Aphidius colemani species complex has been defined as a group of species with pantropical – subtropical distribution which is characterized by low number of grooves (costulae) with specific position on the anterolateral region of the petiole. This group is one of the 10 groups of species (complexes) with unsolved taxonomical status among the genus Aphidius. Morphological and genetic characterization of the Aphidius colemani complex was done by using morphometrics and DNA sequence analysis of the barcoding gene for Cytochrome oxidase I (COI). In total 250 specimens of A. colemani complex from 23 deferent countries on four continents were encompassed with morphometric analysis. By analyzing variability of morphological characters, statistically significant differences were noted in the sense of their informativity in separation of deferent groups of the complex. Molecular analysis was performed on 54 specimens from eight deferent countries. By analyzing sequences of COI gene and the reconstruction of phylogenetic relations, one hidden taxon was detected among the A. colemani complex. Combination morphometric and molecular methods has shown the existence of at least three distinct taxa: Aphidius colemani, Aphidius transcaspicus and Aphidius cf. colemani 1 (new taxon). This new species can be found in Asia (Iran) and South America (Chile). It has been shown that there are no clear connections between genetic differentiation of the parasitoids from this complex and their aphid hosts, as well as between genetic differentiation and geographic distribution. Univerzitet u Beogradu Biološki fakultet Tomanović, Željko, 1966- Petrović, Anđeljko Žikić, Vladimir, 1969- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=153 https://fedorabg.bg.ac.rs/fedora/get/o:5386/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024556722 sr Autorstvo-Nekomercijalno 3.0 Srbija (CC BY-NC 3.0)

oai:eteze.bg.ac.rs:154 2013-07-24T00:00:00Z 1

Galektin-1 i funkcionalna svojstva ćelija trofoblasta čoveka in vitro Galectin-1 and functional properties of human trophoblast cells in vitro. Kolundžić, Nikola M., 1983- gal-1, trofoblast, ćelijska invazija, izolovani citotrofoblast, HTR-8/SVneo, JAr, galektinski profil, gal-8 gal-1, trophoblast, cell invasion, isolated cytotrophoblast, HTR-8/SVneo, JAr, galectin profile, gal-8 Datum odbrane: 26.12.2012. U zoni interakcije majke i fetusa galektin-1 (gal-1) je eksprimiran na način koji ukazuje na njegovu moguću ulogu u ćelijskoj adheziji, migraciji i invaziji trofoblasta, procesima koji su ključni za implantaciju embriona i formiranje funkcionalne placente. Međutim, uloga gal-1 u trofoblastu čoveka dosada nije bila ispitivana, što je predmet istraživanja ovog doktorskog rada. U tu svrhu korišćeni su odgovarajući funkcionalni in vitro testovi adhezije, migracije i invazije na modelima invazivnog trofoblasta (izolovanom citotrofoblastu iz placenti prvog trimestra normalne trudnoće, imortalizovanoj ekstravilusnoj ćelijskoj linija HTR-8/SVneo, i, u manjoj meri, na horiokarcinomskoj ćelijskoj liniji JAr). Obzirom da gal-1 sintetišu i ekstravilusne trofoblastne i decidualne stromalne ćelije in vivo, u ovom radu je ispitivan mogući uticaj kako endogenog (upotrebom antitela prema gal-1 koja blokiraju i funkciju gal-1), tako i egzogenog gal-1 (upotrebom dveju molekulskih formi rekombinantnog humanog gal-1 dokazane biološke aktivnosti, od kojih jedna poseduje lektinsku aktivnost - CS-gal-1, a druga ne - Ox-gal-1) na funkcionalna svojstva trofoblasta in vitro. Značaj lektinskih interakcija za funkciju trofoblastnih ćelija ispitivan je funkcionalnim testovima u prisustvu laktoze (inhibitornog šećera za lektinski tip interakcija galektina). Zbog činjenice da se obrasci ekspresije, kao i funkcije galektina često znatno preklapaju, utvrđen je galektinskog profila invazivnog trofoblasta na nivou RNK i proteina. U ovom radu je po prvi put pokazan funkcionalni značaj nekog od galektina za invazivnost trofoblasta čoveka in vitro, kvalifikujući gal-1 za važnog člana grupe molekula koji učestvuju u trofoblastnoj invaziji. Pokazali smo da endogeni gal-1, kao i dodatni egzogeni gal-1 (obe ispitivane molekulske forme) stimulišu invaziju trofoblasta, što ukazuje na mogućnost da bi i u uslovima in vivo, gal-1, kako trofoblastnog, tako i decidualnog porekla, mogao biti uključen u ovaj proces. Dobijeni rezultati su pokazali i da se ovaj uticaj gal-1 na invazivnu sposobnost trofoblasta ostvaruje pre svega njegovom lektinskom aktivnošću. Ovim radom je po prvi put utvrđen galektinski profil invazivnog trofoblasta koji čine gal-1, gal-3, i do sada u trofoblastu čoveka neidentifikovani član galektinske familije, gal-8. Galectin-1 (gal-1) is expressed at the fetomaternal interface in a manner suggestive of a potential involvement in cell adhesion, migration and invasion of the human trophoblast. These processes are considered essential for the embryo implantation and formation of the functional placenta. However, no studies have examined the role of the gal-1 in the human placenta. Hypothesis that gal-1 may be relevant for trophoblast invasion was addressed by this thesis for the first time. To this end appropriate functional tests of cell adhesion, migration and invasion were performed in vitro, using invasive trophoblast models (isolated first trimester cytotrophoblast, immortalized extravillous HTR-8/SVneo cell line and choriocarcinoma JAr cell line). Since gal-1 is synthesised by both extravillous cytotrophoblast and decidual stromal cells in vivo, selected approaches addressed possible effect of both endogenous and exogenous gal-1. Use of function blocking anti-gal-1 antibody provided an insight into participation of endogenous gal-1, while supplementation by either molecular form of biologically active recombinant human gal-1, CS-gal-1 (with lectin activity) or Ox-gal-1 (without lectin activity) indicated relevance of exogenous gal-1 for trophoblast invasion in vitro. The importance of lectin-type interactions was investigated primarily using lactose (an inhibitory sugar for galectins). Since the expression patterns and functions of galectins often overlap, galectin profile of the invasive trophoblast at RNA and protein levels was established here. This is the first study to address the functional relevance of any galectin for human trophoblast invasivness in vitro, qualifying gal-1 as an important member of the trophoblast cell invasion machinery. It is documented here that endogenous gal-1, as well as additional exogenous gal-1 (both forms, but particularly the form with lectin activity) participate in trophoblast invasion, suggesting possible involvement of trophoblastic and decidual gal-1 in this process in vivo. Galectin profile of the invasive trophoblast was established here for the first time, which comprised of gal-1, gal-3 and gal-8 Univerzitet u Beogradu Biološki fakultet Vićovac-Panić, Ljiljana Korać, Aleksandra, 1964- Korać, Aleksandra, 1964- Bojić-Trbojević, Žanka 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=154 https://fedorabg.bg.ac.rs/fedora/get/o:5390/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024554930 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:155 2013-07-24T00:00:00Z 1

Genetički markeri oksidativnog stresa kod bolesnika sa manifestnim dijabetesom tipa 2 i aterosklerozom Genetic markers of oxidative stress in patients with manifested diabetes type 2 and atherosclerosis Grubiša, Ivana I., 1980- ateroskleroza, diabetes mellitus tip 2, oksidativni stres, genski polimorfizmi, apoE, pon1, GSTM1, GSTT1, GSTP1 atherosclerosis, diabetes mellitus type 2, oxidative stress, gene polymorphisms, apoE, pon1, GSTM1, GSTT1, GSTP1 Datum odbrane: 26.4.2013. Ateroskleroza je kompleksno i multifaktorsko oboljenje koje obuhvata veliki broj tipova ćelija kao i brojne fiziološke procese. Veruje se da oksidativni stres igra važnu ulogu u inicijaciji i progresiji ateroskleroze. Kardiovaskularne bolesti (CVD) predstavljaju vodeći uzrok smrtnosti u Srbiji i pronalaženje markera oksidativnog stresa, uključujući i genske varijante, doprinelo bi smanjenju broja obolelih. Studija asocijacije, koja je obuhvatala 140 obolelih od diabetes mellitus tip 2 sa kardiovaskularnim komplikacijama (DM+A), 60 obolelih od neke od kliničkih manifestacija ateroskleroze (A) i 100 zdravih kontrola (K) je sprovedena da bi se utvrdila značajnost polimorfizama gena koji su povezani sa oksidativnim stresom, metabolizmom lipida i detoksifikacijom kao markera oksidativnog stresa i faktora rizika za nastanak oboljenja. Za studiju su odabrani polimorfizmi gena čiji produkti imaju antioksidativnu ulogu u plazmi (pon1 Q192R, L55M i C(-107)T), antioksidativnu ulogu i ulogu u metabolizmu lipida u plazmi i ćeliji (apoE 112/158 polimorfizam) i antioksidativnu i detoksifikujuću ulogu u ćeliji (GSTM1*0, GSTT1*0 i GSTP1 Ile105Val). Genomska DNK je izolovana ili iz ćelija periferne krvi ili iz epitelnih ćelija bukalne sluzokože. Genotipizacija je rañena restrikcionom digestijom PCR produkata i analizom dužine restrikcionih fragmenata (PCR-RFLP) na agaroznom ili poliakrilamidnom gelu i real-time PCR metodom. Hi-kvadrat i Fišerov egzaktni test su upotrebljeni za utvrñivanje razlika u distribuciji učestalosti ispitivanih genotipova i alela, a logističkom regresionom analizom utvrñivan je rizik za oboljevanje. Atherosclerosis is a complex and multifactorial disorder that involves many cell types and organs as well as many physiological processes. It is believed that the oxidative stress plays a critical role in the initiation and progression of atherosclerosis. Cardiovascular diseases (CVD) are the leading cause of death in Serbia and discovering oxidative stress markers, including gene variants, would contribute to reducing the number of patients. A association study, comprised 140 patients with diabetes mellitus type 2 and cardiovascular complications (DM+A), 60 patients with clinical manifestations of atherosclerosis (A) and 100 healthy individuals (K), has been undertaken in order to estimate the relevance of polymorphisms in genes related to oxidative stress, lipid metabolism, and detoxification as oxidative stress markers and disease risk factors. Polymorphisms in genes whose products exert an antioxidative role in the plasma (pon1 Q192R, L55M i C(-107)T), in both plasma and cells (apoE 112/158 polymorphisms) and antioxidative and detoxication role in cells (GSTM1*0, GSTT1*0 i GSTP1 Ile105Val) have been selected for the study. Genomic DNA was isolated from peripheral blood cells or from buccal epithelial cells. The genotyping was performed using restriction digestion of PCR products and by analysis of restriction fragment length (PCR-RFLP) on agarose or polyacrilamide gel electrophoresis and the real-time PCR method.Chi-square and Fisher exact test were used for determination of differences in the analyzed genotype and allele distribution frequencies, and logistic regression analysis was used for disease risk assessment. Univerzitet u Beogradu Biološki fakultet Milašin, Jelena, 1957- Stamenković-Radak, Marina, 1958- Vučinić, Nada Novaković, Ivana, 1961- 2013 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=155 https://fedorabg.bg.ac.rs/fedora/get/o:5392/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/43481103 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:156 2013-07-24T00:00:00Z 1

Modelovanje ekoloških niša Podarcis sicula i P. melisellensis (Sauria, Lacertidae) u eumediteranu i submediteranu istočnog Jadrana Ecological niche modelling of Podarcis sicula and P. melisellensis (Sauria, Lacertidae) in the eumediterranean and submediterranean of the eeastern Adriatic sea Stamenković, Srđan Ž., 1961- Podarcis sicula, Podarcis melisellensis, modeliranje ekoloških niša, modeliranje stanišne povoljnosti, analiza rizika izumiranja populacija Podarcis sicula, Podarcis melisellensis, ecological niche modelling, habitat suitability modelling, population viability analysis Datum odbrane: 18.4.2013. Rad obuhvata modelovanje ekoloških niša dve vrste guštera Podarcis sicula i P. melisellensis na dva područja kopnene oblasti istočnog Jadrana povezane sa analizom rizika izumiranja metapoulacionih demografskih modela formiranih na osnovu prostornih niša. Obe vrste su su od opisivanja u XIX veku bile epizodično predmet zoogeografskih, ekoloških i evolucionih istraživanja u Jadranskoj oblasti. Brojni dosad prikupljeni bionomski i ekološki podaci o obe vrste na istraživanom području, međutim, uglavnom nisu stavljeni u celovit kvantitativni koncept, velikim delom ostajući na nivou manje ili više detaljnog kvalitativnog opisa. Postojeći kvantitativni podaci, prikazani su kao “lateralni” ili “akcesorni” rezultati istraživanja čiji je osnovni cilj bio sasvim drugačiji te je njihova upotrebna vrednost u potpunosti podređena kontekstu realizovanih istraživanja. Posebno se to odnosi na autekološka i populaciono-ekološka istraživanja. Ostrvske populacije su znatno bolje istražene od kopnenih. Realizujući kvantitativno modeliranje niša kopnenih populacija, pokušali smo da makar malo taj problem ublažimo. U modelovanju ekoloških niša korišćeno je 47 kvantitativnih i 9 kvalitativnih EGV, u zavisnosti od metode, koje su formirane na osnovu globalnih baza podataka. Obuhvaćena područja, oko 100 km2 po površini, nalazila su se u Poljicama (okolina Splita, Hrvatska) i šireg regiona Boke Kotorske (Crna Gora) na kojoj su detaljno mapirane obe vrste. Korišćene su tri metode sa prisustvom vrsta (P/O, ENFA, MaxEnt i GARP), četiri koje zahtevaju prisustva/odsustva (P/A, SpFA, PLS, GRM, DA), i tri koje mogu koristiti oba tipa podataka (P/O ili P/A, GAM, MARS, BRT). Na osnovu profila stanišne povoljnosti formirane su detaljne karte prostornih niša. Sve metode su identifikovale centre povoljnostog staništa istog ili sličnog položaja i obuhvata. P/A metode su identifikovale mnogo šire zone suboptimalnih staništa za obe vrste na oba područja. EGV korišćene za analizu su ocenjene po čestoći odabira u modelima i minimalni skup promenljivih koji daju pouzdane predikcije je: ALT, *OVER1, *CONVEX1, SLOPE10, BIO1, *4, *5, *7, *8, *9, *10, *11, *12, *19, WB, PET, TOWNSFQ1, *TOPODST, *BLENGTH, AGRIFQ1, *TOPODST, *BLENGTH, OPENFQ1, *TOPODST, *BLENGTH, SPARSEFQ1, *TOPODST, *BLENGTH. Svi modeli niša su bili statistički značajni, a po uspešnosti predikciji ističu se MARS, PLS, GRM. Za područje Hrvatske, sve metode imaju lošiju uspešnost nego za područje Crne Gore. Modeli niša bili su uspešniji za Podarcis sicula na oba područja. Modeli ekoloških niša nisu transportabilni po područjima, zbog suviše velikih razlika u intenzitetu delovanja i prostornom rasporedu ekoloških faktora. Ecological niche models were generated for two lizard species, Podarcis sicula i P. melisellensis, in two mainland areas of the eastern Adriatic, and coupled with spatially-explicit PVA based on habitat suitabilty profiles generated by ENM. Both species have, since their description in the XIX century, been episodically studied from zoogeographical, ecological, and evolutionary aspects. However, a wealth of bionomic data collected by investigators was qualitative, lacking a comprehensive quantitative framewok, and as such are of limited value. The available bionomic and ecological data was largely presented as "lateral" or "accessory" data collected for a different scientific objective, and their utility is largely determined by the context of that research. Specifically, that problem pertains to the utility of reported autecological and population-ecological data. Mainland populations of both species were also much less studied than the island populations in the Adriatic. We addressed this problem by conducting quantitative niche-modelling research based on the mainland. For ecological niche modelling we used 47 quantitative and 9 qualitative EGV's, depending on the method, which were generated from global datasets. Both regions were cc. 100 km2 in area, and were located in Poljice (Split, Croatia) and the general region of Boka Kotorska (Montenegro) for we had which detailed distribution data. Three methods requiring presence/only data were used (P/O, ENFA, MaxEnt i GARP), four requiring presence/absence (P/A, SpFA, PLS, GRM, DA), and three which could use both (P/O or P/A, GAM, MARS, BRT). Habitat suitability profiles generated by these methods were used to map the spatial niches. All methods identified identical or very similar core areas of HS. P/A methods were much more liberal in assigning adjacent suboptimal HS zones for both species in both areas. EGV's selected by the methods were scored by frequency of selection in models, and a minimal subset generating reliable predictions was identified: ALT, *OVER1, *CONVEX1, SLOPE10, BIO1, *4, *5, *7, *8, *9, *10, *11, *12, *19, WB, PET, TOWNSFQ1, *TOPODST, *BLENGTH, AGRIFQ1, *TOPODST, *BLENGTH, OPENFQ1, *TOPODST, *BLENGTH, SPARSEFQ1, *TOPODST, *BLENGTH. All niche models were satistically significant, with MARS, PLS, GRM generally preforming better than the rest. For Croatia, all methods had lower performance than for Montenegro. Niche models were more reliable for Podarcis sicula in both areas. Large differences in context due to differences in intensity and spatial distibution of EGV's precluded model transportability over areas. Univerzitet u Beogradu Biološki fakultet Kataranovski, Dragan, 1950- Jovanović, Aleksandar, 1949- Krpo-Ćetković, Jasmina, 1961- Vukov, Tanja Lakušić, Dmitar, 1965- 2013 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=156 https://fedorabg.bg.ac.rs/fedora/get/o:5393/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/43480079 sr Autorstvo 3.0 Srbija (CC BY 3.0)

oai:eteze.bg.ac.rs:161 2013-09-30T00:00:00Z 1

Razvoj modela za monitoring i evaluaciju informacionog društva Srbije Development of a model for monitoring and evaluation of the information society in Serbia Savić, Ninoslava, 1957- informaciono društvo, merenje, benčmarking indikatori, evaluacija, digitalne podele, indeks digitalne polarizacije, klaster analiza, I- odstojanje information society, measurement, benchmarking indicators, evaluation, digital divide, Digital Polarization Index, cluster analysis, I-distance method Datum odbrane: 2.04.2013. Predmet disertacije pripada oblasti informacionog društva, njegovog razvoja i mehanizama za praćenje i merenje tog razvoja. Doktorska disertacija prikazuje dosadašnja istraživanja i teorije o informacionom drušvu i njegovoj evoluciji i oblicima, faktorima njegovog razvoja i međunarodnim inicijativama koje usmeravaju i usaglašavaju njegov globalni razvoj. Proučavajući oblast merenja informacionog društva kao složene pojave opisane skupom međusobno korelisanih pokazatelja, u tezi se traži najpogodnija metrika kojom bi se prevazišla složenost i olakšalo praćenje, vrednovanje i izvođenje zaključaka o aktuelnom stanju informacionog društva. Pored evolucije i klasifikacije benčmarking indikatora, kao elementarnih činilaca svake metodologije za merenje informacionog društva, u tezi je dat i pregled najznačajnijih svetskih metodologija za vrednovanje informacionog društva. Centralno mesto predstavlja projektovanje originalnog modela koji definiše postupke neophodne za praćenje i evaluaciju razvoja informacionog društva Srbije. Ovaj model podrazumeva: · teorijsku zasnovanost, · kompatibilnost sa standardima Evropske Unije koja omogućava učešće u međunarodnim projektima, analizama i poređenjima, · prilagođenost specifičnostima Srbije, njenom aktuelnom stanju informacionog društva mogućnostima za ulaganje u dalji razvoj. Definisanje modela za merenje i evaluaciju informacionog društva Srbije obuhvatilo je: · selekciju skupa indikatora informacionog društva (IKT indikatora) u skladu sa zahtevima Evropske Unije, uz prilagođavanje specifičnostima i razvojnm mogućnostima Srbije, · transformaciju skupa IKT indikatora, koja omogućava njihovo rangiranje prema značaju za praćenje informacionog društva, · izdvajanje podskupa najznačajnijih IKT indikatora, · definisanje podmodela za kvantitativno izražavanje nivoa digitalnih podela preko sintetičkog pokazatelja - indeksa digitalne polarizacije. Projektovani model je verifikovan implementacijom na slučaju Srbije, kroz praćenje i analizu stanja razvoja informacionog društva u petogodišnjem periodu. Tom prilikom je izvršeno: · statističko praćenje, merenje i obrada relevantnih podataka, · analiza rezultata istraživanja koja je omogućila sagledavanje aktuelnog stanja, otkrivanje i kvantifikovanje ‘kritičnih tačaka’ u razvoju informacionog društva Srbije, kao i predviđanje njegovog budućeg razvoja. The main topic of the doctoral dissertation belongs to the field of information society, its development and mechanisms for tracking and measuring its advancements. This dissertation summarizes the existing research and theories developed on the topic of information society, its evolution and variety of forms, factors that determine its growth and various international initiatives aimed at guiding the global progress of information society. By investigating the possibilities to quantify the information society as a complex concept defined by the set of mutually correlated indicators, this dissertation research the most convenient metrics that would enable observing, measuring and evaluating the actual condition of information society. In addition to providing the classification and the evolution path of the benchmarking indicators that represent the cornerstone of every methodology aimed at quantifying the information society, this dissertation contains the overview of the most relevant methodologies used for evaluating the information society worldwide. However, the main focus of this work represents the design of the original model which specifies actions required to track and evaluate the advancements in the information society of Serbia. This model assumes: · theoretical foundation, · compatibility with the European Union (EU) standards, which enables its broad use in the projects with international cross-country analyses and comparisons, · compliance with the particularities of Serbian information society and the existing possibilities of Serbia for investment and further development. Formulation of the model has encompassed: · selection of the set of Information Society Indicators (ISI) in accordance with EU standards, but with modification with regards to characteristics and development possibilities of Serbia, · transformation of the ISI set that enables their ranking according to the significance for monitoring of the information society, · extracting a subset of the most relevant ISI, · Defining the sub-model that quantifies the degree of digital divide through an unique compound indicator - Digital Polarization Index (DPI). Univerzitet u Beogradu Fakultet organizacionih nauka Radojičić, Zoran. 1967- Vukmirović, Dragan. 1962- Surla, Dušan. 1942- 2013 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=161 https://fedorabg.bg.ac.rs/fedora/get/o:5394/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/515340186 sr Autorstvo-Nekomercijalno-Deliti pod istim uslovima 3.0 Srbija (CC BY-NC-SA 3.0)

oai:eteze.bg.ac.rs:162 2013-07-24T00:00:00Z 1

Molekularni mehanizmi patogeneze mijeloproliferativnih neoplazija : poremećaj ekspresije gena uključenih u proliferaciju i apoptozu Molecular mechanisms of pathogenesis of myeloproliferative neoplasms: deregulation of genes involved in cell proliferation and apoptosis Spasovski, Vesna M., 1971- Mijeloproliferativne neoplazije, JAK2-V617F mutacija, 46/1 haplotip, transkripciona regulacija, ekspresija JAK2 gena, apoptoza Myeloproliferative neoplasms, JAK2-V617F-mutation, 46/1 haplotype, transcriptional regulation, expression of the JAK2 gene, apoptosis Datum odbrane : 27.12.2012. Mijeloproliferativne neoplazije (MPN) su hronični hematološki maligniteti koji se odlikuju autonomnom proliferacijom opredeljenih progenitora hematopoeze i aberantnom aktivacijom tirozin kinaznih signalnih puteva u kombinaciji sa snažnim odgovorom na citokine i faktore rasta. Tri bolesti predstavljaju MPN u užem smislu: policitemija vera (PV), esencijalna trombocitemija (ET) i mijelofibroza (MF). Jedna od komplikacija ovih oboljenja je njihova kasna evolucija u akutnu mijeloidnu leukemiju (AML). Važno obeležje ovih bolesti ja prisustvo „missense“ JAK2-V617F mutacije u sve tri bolesti, a procenat zastupljenosti mutacije po bolestima je različit. TakoĎe pokazano je da kod ovih pacijenata postoji tzv. efekat “doze gena”, odnosno da različit nivo V617F alela utiče kliničku sliku bolesti. JAK2-V617F mutacija dogaĎa se u 80% slučajeva na specifičnom haplotipu koji je nazvan 46/1 haplotip. Na koji način ovaj niz SNP-ova, koji se nalaze u JAK2 genu, predisponira nastajanje mutacije kao i njen uticaj na fenotip MPN, još nije utvrĎeno. Jedan od mogućih mehanizama je uticaj ovog haplotipa na transkripciju. Posebnu pažnju u okviru 46/1 haplotipa je privukao SNP rs12343867, koji u potpunosti asocira sa MPN. Proces apoptoze je deregulisan u hematološkim malignitetima, što dovodi do rezistencije malignih ćelija na signale smrti i obezbeĎuje im duži život u odnosu na normalne ćelije. Proces apoptoze nije detaljno izučen kod MPN, mada se zna da je direktno pogoĎen JAK2-V617F mutacijom. Naime, glavni signalni put preko STAT5 (Signal Transducers and Activators of Transcription) proteina direktno aktivira anti- apoptotski BCL2-xL protein, čime se smanjuje apoptoza. Deregulacija ostalih apoptotskih puteva u MPN nije u potpunosti rasvetljena Myeloproliferative neoplasms (MPN) are chronic hematological malignancies that are characterized by autonomous proliferation of committed hematopoietic progenitors and aberrant activation of tyrosine kinase signaling pathways, in combination with a strong response to cytokines and growth factors. Three major entities constitute MPN: polycythaemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). One of the complications of these diseases is their late evolution into acute myeloid leukemia. Important feature of these diseases is the presence of missense mutation JAK2- V617F and its variable representation among MPN entities. It is also shown that there is socalled effect of "gene dosage" in these patients, meaning that a different level of V617F alleles influences the clinical picture of the disorders. JAK2-V617F mutation occurs in 80% of cases on a specific haplotype, called 46/1 haplotype. Exact mechanism of action of this set of SNPs, that are located within the JAK2 gene, has not been determined yet. One of the possible mechanisms could be that it effects transcription. Among eight SNPs, included in this haplotype, SNP rs12343867 has drawn special attention because of its strong association with the MPN. The process of apoptosis is deregulated in hematological malignancies, leading to resistance of cancer cells to death signals, thus providing them a longer life span compared to normal cells. The process of apoptosis has not been extensively studied in MPN, although it is known that it is directly affected by the JAK2-V617F mutation. Specifically, the main signaling pathway through STAT5 protein directly activates anti-apoptotic BCL2- xL protein, thereby reducing apoptosis. Deregulation of other apoptotic pathways in MPN is not fully understood Univerzitet u Beogradu Biološki fakultet Pavlović, Sonja. 1949- Pavlović, Sonja. 1949- Savić-Pavićević, Dušanka, 1972- Savić-Pavićević, Dušanka, 1972- Nikčević, Gordana 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=162 https://fedorabg.bg.ac.rs/fedora/get/o:5396/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024559538 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:163 2013-09-30T00:00:00Z 1

Interoperabilnost u elektronskom poslovanju statističkih sistema E-business interoperability in statistical systems Milojković, Jelena, 1967- G2G integracija, interoperabilnost statističkih sistema, SOA G2G Integration, Interoperability of Statistical Systems, SOA Datum odbrane: 09.09.2012. Predmet ove disertacije je definisanje modela interoperabilnog elektronskog poslovanja statističkih sistema baziranog na servisno orijentisanoj arhitekturi i veb-servisima. Istraživanje je prilagođeno za primenu u statističkom sistemu Srbije. Zvanična statistika je neophodan element u informacionom sistemu svakog demokratskog društva u obezbeđivanju podataka o ekonomskoj, demografskoj i socijalnoj situaciji i o stanju životne sredine. Najvažniji zadatak zvanične statistike jeste da pruži realnu sliku društvenih i ekonomskih kretanja u zemlji i da obezbedi pouzdanu osnovu za analizu i donošenje odluka na raznim nivoima društva, od državne uprave i drugih institucija, preko poslovnih subjekata, sve do zainteresovanih građana. Zvanična statistika Srbije, pored ostalog, polazi i od principa koji su definisani u dokumentu Ekonomsko-socijalnog saveta UN – Osnovni principi zvanične statistike, kao i u dokumentu Evropske komisije – Kodeks prakse evropske statistike Većina zemalja ima jednu ili više nacionalnih statističkih organizacija (engl. NSIs), koje čine nacionalni statistički sistem te zemlje. Osnovni zadaci NSIs su: prikupljanje, obrada i organizovanje statističkih podatka, a zatim njihovo stavljanje na korišćenje različitim zajednicama korisnika. U okviru svake NSI, produkcija statistike najčešće funkcioniše kroz različite proizvodne linije i procese za različite statističke oblasti. Poslovne arhitekture većine NSI su zasnovane na takozvanom stove-pipe modelu. U takvom modelu, za svaku statističku oblast u okviru NSI se formira posebna i nezavisna proizvodna linija. Za svaki domen, ceo proces proizvodnje od projektovanja istraživanja preko prikupljanja i obrade podataka potrebnih za objavljivanje, odvija se nezavisno od drugih domena a svaki ima svoje sopstvene izvore podataka i korisnike. Elektronska razmena statističkih podataka je sve češći i važniji vid komunikacije između različitih statističkih službi. Ova razmena je stalno praćena nedostatkom interoperabilnosti i potrebom za konvertovanjem podataka. Ovim se naglašava potreba za usvajanjem skupa zajedničkih standarda za razmenu i deljenje statističkih podataka i meta-podataka, čime bi se statistički procesi učinili efikasnijim. Cilj je da se uspostavi skup standarda koji su široko prihvaćeni, što omogućava ne samo lak i blagovremen pristup podacima već i pristup meta-podacima koji opisuju te podatke i čine ih smislenijim i upotrebljivijim. Servisno-orijentisana arhitektura (SOA) statističkih informacionih sistema omogućava interoperabilnost na nivou aplikacija i na nivou poslovnih procesa, dok je interoperabilnost na semantičkom nivou obezbeđena kreiranjem zajedničke domenske ontologije i razvojem zajedničkog modela podataka nad domenskom ontologijom. This thesis defines model of interoperable e-business statistical systems based on service oriented architecture and web services. Research is adapted for application in statistical system of the Republic of Serbia. Official statistics is one of the key elements in information system of each democratic society. This component provides data related to economical, demographical, social situation and state of the environment. The most important task for official statistics is to give real picture of social and economic movements in state. Further, it aims to provide reliable basis for analysis and decision making at different levels, from public government and other institutions to business entities and citizens. Official statistics in the Republic of Serbia works on principles defined in document of Economic-social council of UN - basic principles of official statistics, as well as in document of European commission – Practical codex of European statistics. Majority of countries have one or more statistical institutions on national level (NSI) that together constitute national statistical system of that country. Main tasks of such systems are: gathering, storing and analysis of statistical data, and providing the data to different groups of users. Within each of NSI, statistical production is performed through various production lines and processes for different statistical areas. Mostly, business architecture of NSIs are based on so called stove-pipe model. In this model, independent production line is formed for each statistical area within NSI. For each domain, full process of production from research planning to gathering and analysis of data that are necessary for publishing, is realized independently of other domains. Each domain posses its own data, sources and users. Electronic exchange of statistical data is very common way of communication among statistical services. The exchange is permanently followed by lack of interoperability and need for data conversion. This thesis proposes for adopting common standards for statistical data sharing and exchange. Main goal is to create set of standards that are broadly acceptable, so to enable quick and prompt access to data and metadata. Service-oriented architecture of statistical information system enables interoperability both on application level and business process level. Interoperability on semantic level is provided by designing common domain ontology and by developing common data model on domain ontology. Univerzitet u Beogradu Fakultet organizacionih nauka Radenković, Božidar. 1958- Zrakić, Marijana Despotović- Vukmirović, Dragan. 1962- Radojičić, Zoran. 1967- Stanojević, Milorad, 1947- 2013 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=163 https://fedorabg.bg.ac.rs/fedora/get/o:5398/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/515210650 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:164 2013-07-24T00:00:00Z 1

Uticaj adrenalina i efedrina na pojavu primarnih oštećenja DNK u limfocitima čoveka in vitro Influence of adrenaline and ephedrine on primary DNA damage of lymfocytes of man in vitro Radaković, Milena, 1983- adrenalin, efedrin, genotoksičnost, Komet test, antioksidansi, inhibitori reparacije adrenaline, ephedrine, genotoxicity, Comet assay, antioxidants, inhibitors of DNA repair Datum odbrane: 20.3.2013. U ovom radu cilj istraživanja je bilo ispitivanje primarnih oštećenja DNK izolovanih limfocita čoveka pod uticajem adrenalina i efedrina. Oštećenja DNK su evaluirana primenom in vitro Komet testa. Ispitivan je širok spektar koncentracija adrenalina i efedrina (u rasponu od 0,0005 μM do 500 μM) u različitim vremenskim intervalima (15 min, 60 min, 120 min, 240 min i 24 sata). Najizraženije oštećenje DNK ustanovljeno je nakon 15 min tretmana adrenalinom, pri čemu su sve koncetracije izuzev najniže (0.0005 μM) dovele do povećane migracije DNK. Nakon 60 min, 120 min, 240 min tretmana adrenalinom indukovano je oštećenje DNK u opsegu od 5 do 300 μM. Najslabiji efekat ispoljen je nakon 24 sata, tako da su samo najviše koncetracije adrenalina (150 μM i 300 μM) dovele do povećanog stepena oštećenja DNK. Radi utvrđivanja mogućeg učešća reaktivnih kiseoničnih vrsta (ROS) u indukovanju DNK oštećenja pod dejstvom adrenalina upotrebili smo antiokisanse katalazu (100 IU i 500 IU) i kvercetin (100 μM i 500 μM). Kotretman limfocita adrenalinom (300 μM) i antioksidansima nakon 15 ili 60 minuta doveo je do značajnog smanjenja količine DNK u repovima kometa. Prema tome, može se zaključiti da adrenalin ispoljava svoje genotoksične efekte indukcijom reaktivnih kiseoničnih vrsta i da se neka oštećenja poprave tokom prva četiri sata nakon tretmana adrenalinom. Za razliku od adrenalina, efedrin nije doveo do povećanja migracije DNK u odnosu na negativnu kontrolu tokom različitih vremenskih intervala. Jedino je koncetracija efedrina od 500 μM nakon 15 minuta tretmana indukovala oštećenje DNK koje je bilo statistički značajno. The objectives of these investigations were to investigate primary DNA damage in isolated human lymphocytes exposed to adrenaline and ephedrine. DNA damage was evaluated by the in vitro Comet assay. A broad spectrum of adrenaline and ephedrine concentrations (range from 0.0005 μM to 300 μM) were examined in the Comet assay for various treatment times (15 min, 60 min, 120 min, 240 min and 24 h). The most profound DNA damage was observed after 15 min of adrenaline treatment, as all concentrations tested except the lowest one (0.0005 μM) caused an increase in DNA migration. After 1 h, 2 h and 4 h of treatment, adrenaline induced DNA damage at concentration range from 5 μM to 300 μM. The slightest DNA damage was observed after 24 h of adrenaline treatment, therefore only the highest concentrations of adrenaline (150 μM and 300 μM) caused increased level of DNA damage. In order to evaluate the potential contribution of reactive oxygen species (ROS)-induced DNA damage exposed to adrenaline, we used antoxidants catalase (100 IU and 500 IU) and quercetin (100 μM and 500 μM). Co-treatment of lymphocytes with adrenaline (300 μM) and antioxidants for 15 or 60 min, significantly reduced the quantity of DNA in the comet tails. Therefore, it can be concluded that adrenaline exhibits genotoxic effects mainly through induction of reactive oxygen species and that some of the DNA damage is repaired during the first four hours following the treatment with adrenaline Univerzitet u Beogradu Biološki fakultet Anđelković, Marko 1945- Živković, Lada, 1970- Đelić, Ninoslav, 1962- Đelić, Ninoslav, 1962- Stamenković-Radak, Marina, 1958- 2013 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=164 https://fedorabg.bg.ac.rs/fedora/get/o:5399/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024571058 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:165 2020-03-19T00:00:00Z 1

Gen za veliku subjedinicu šaperonina (groEL gen) kao dodatni molekularni marker za diferencijaciju fitoplazmi srodnih 'Candidatus Phytoplasma asteris' Molecular chaperonin large subunit gene (gro EL gene) as an additional marker for differntiation of 'Canidatus Phytoplasma asteris' - related strains Mitrović, Jelena R., 1981- varijabilnost gena, RFLP, groELI podgrupe, tufI podgrupe, rpI podgrupe, secYI podgrupe, Stolbur fitoplazme, filogenetska analiza gene variability, RFLP, groELI subgroups, tufI subgroups, rpI subgroups, secYI subgroups, Stolbur phytoplasma, phylogenetic analysis Datum odbrane: 15.4.2013. Na teritoriji Republike Srbije su u periodu od 2009. do 2011. godine sakupljeni uzorci biljaka sa simptomima karakterističnim za prisustvo fitoplazmi. Upotrebom PCR metode pomoću univerzalnih prajmera P1/P7 i R16F2n/R16R2 u njima su detektovane fitoplazme. Upotrebom restrikcionih enzima Tru1I, HhaI, RsaI i Tsp509I na R16F2n/R16R2 amplikone, ove fitoplazme su na osnovu dobijenih restrikcionih profila identifikovane kao Aster yellows fitoplazme (ribozomalna grupa 16SrI), podgrupe 16SrI-B, I-C i I-P, odnosno kao Stolbur fitoplazme (ribozomalna grupa 16SrXII). Upotrebom iste PCR-RFLP metode kod 19 sojeva Aster yellows fitoplazmi iz kolekcije i tri soja poreklom iz šargarepe iz Srbije, potvrĎena je pripadnost podgrupama 16SrI-A, I-B, I-C i I-F preuzeta iz literature. TakoĎe je utvrĎena pripadnost odreĎenoj podgrupi kod četiri soja iz kolekcije, koji se prvi put koriste u analizi i o kojima nema literaturnih podataka. Upotrebom novodizajniranih prajmera AYgroesF/AYampR i AYgroelF/AYgroelR umnoţen je groEL gen kod sva 34 testirana soja Aster yellows fitoplazmi. Analizom restrikcionih profila dobijenih pomoću Tru1I i AluI restrikcionih enzima na AYgroelF/R amplikone, utvrĎeno je postojanje šest, odnosno osam različitih profila na osnovu kojih su svi testirani sojevi svrstani u devet groELI podgrupa (groELI-I do groELI-IX). Na osnovu groEL gena podgrupe 16SrI-A i I-C su dalje diferencirane u dve groELI podgrupe, 16SrI-B u tri, dok podgrupe 16SrI-M i I-L nisu pokazale nikakve meĎusobne razlike u odnosu na jedan deo podgrupe 16SrI-B. Podgrupe 16SrI-F i I-P se razlikuju od ostalih podgrupa i na nivou groEL gena kao i na nivou 16S rDNK. TakoĎe je utvrĎeno da sedam novodetektovanih sojeva Aster yellows fitoplazmi iz Srbije pripada podgrupama groELI-III, I-VII i I-IX. Analizom tuf gena, dela rp operona i secY gena kod 22 odabrana od 34 testirana soja soja Aster yellows fitoplazmi moguće je testirane sojeve klasifikovati u šest tufI i sedam rpI i secYI podgrupa na osnovu MboI, Tsp509I i Tru1I restrikcionih profila za tuf gen, HhaI, AluI i Tsp509I za rp gen i Tsp509I i Tru1I za secY gen. Podgrupa 16SrI-A je dalje diferencirana u dve tufI podgrupe, odnosno 16SrI-A i I-B u po dve rpI i secYI podgrupe, dok podgrupe 16SrI-B, I-M i I-L nisu pokazale nikakve meĎusobne razlike. Podgrupe 16SrI-C, I-F i I-P se razlikuju od ostalih podgrupa i na nivou sva tri testirana gena kao i na nivou 16S rDNK The plant samples with symptoms typical for phytoplasma infection were collected in Serbia from 2009 till 2011. In those samples phytoplasmas were detected by PCR technique with universal primers P1/P7 and R16F2n/R16R2 and identified according to their Tru1I, HhaI, RsaI and Tsp509I restriction profiles of digested R16F2n/R16R2 amplicons as Aster yellows phytoplasma (ribosomal group 16SrI), subgroups 16SrI-B, I-C and I-P or as Stolbur phytoplasma (ribosomal group 16SrXII). Applying the same PCR-RFLP method on 19 strains of Aster yellows phytoplasmas from collection and three strains from carrot from Serbia, it was confirmed that this strains belong to subgroups 16SrI-A, I-B, I-C and I-F as stated in literature. Also the subgroups were determined for four strains from collection that are used in analyses for the first time and that have no literature data. Using newly designed primers AYgroesF/AYampR and AYgroelF/AYgroelR, the groEL gene was successfully amplified in all 34 strains of Aster yellows phytoplasma tested. RFLP analyses of AYgroelF/AYgroelR amplicons with Tru1I i AluI restriction enzymes revealed existence of six and eight different restriction profiles, respectively, according to which all tested strains were classified in nine groELI subgroups (groELI-I till groELI-IX). On the basis of groEL gene, subgroups 16SrI-A and I-C were further differentiated into two groELI subgroups, 16SrI-B into three, while subgroups 16SrI-M and I-L showed no difference to some strains belonging to subgroup 16SrI-B. Subgroups 16SrI-F and I-P could be differentiated from other subgroups on the basis of groEL gene as on the basis of 16S rDNA. The seven newly detected Aster yellows strains from Serbia were affiliated to subgroups groELI-III, I-VII and I-IX. RFLP analyses with MboI, Tsp509I and Tru1I restriction enzymes of tuf gene, HhaI, AluI and Tsp509I of rp gene and Tsp509I and Tru1I of secY gene, classified 22 selected Aster yellows strains into six tufI subgroups and seven rpI and secYI subgroups. Subgroup 16SrI-A was further differentiated into two tufI subgroups and subgroups 16SrI-A and I-B were further differentiated into two rpI and secYI subgroups each. On the other hand subgroups 16SrI-B, I-M and I-L showed no mutual differences, while subgroups 16SrI-C, I-F and I-P could be differentiated from other subgroups on the basis of all three genes tested as on the basis of 16S rDNA. RFLP analysis of tuf gen with HpaII restriction enzyme showed that all 116 tested Stolbur phytoplasma strains from Serbia belong to tuf type II variant. For further analyses, 39 Stolbur strains were selected out of 116 detected and two strains from grapevine from Croatia were also included in analyses as tuf type I reference strains to gain a larger picture of variability of groEL gene in Stolbur phytoplasmas. Univerzitet u Beogradu Biološki fakultet Radović, Svetlana, 1958- Duduk, Bojan, 1976- Stamenković-Radak, Marina, 1958- 2013 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=165 https://fedorabg.bg.ac.rs/fedora/get/o:5400/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/43480591 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:167 2013-07-24T00:00:00Z 1

Mehanizam zaštitnog dejstva arilpiperazinskih liganada za dopaminske D2 receptore u azot monoksidom i 6-hidroksidopaminom izazvanoj smrti SH-SY5Y ćelija humanog neuroblastoma Protective mechanism of arylpiperazine dopaminergic D2ligands on nitric oxide and 6-hydroxydopamine induced SH-SY5Y human neuroblastoma cell death Tovilović, Gordana I., 1978- arilpiperazini, neuroprotekcija, azot monoksid, oksidativni stres, 6-hidroksidopamin, apoptoza, autofagija, dopaminski D2 receptori arylpiperazines, neuroprotection, nitric oxide, oxidative stress, 6-hydroxydopamine, apoptosis, autophagy, dopamine D2 receptors Datum odbrane: 28.12.2012. U ovom radu je ispitivan uticaj 20 novosintetisanih arilpiperazinskih dopaminergičkih liganada na vijabilnost humanih SH-SY5Y neuroblastomskih ćelija tretiranih donorom azot monoksida (engl. nitric oxide, NO) natrijum nitroprusidom (engl. sodium nitroprusside, SNP) i uzročnikom oksidativnog stresa dopaminergičkim neurotoksinom 6-hidroksidopaminom (6-OHDA). Supstanca koje je pružala najjaču zaštitu od donora NO je bio N-{4-[2-(4-fenil-piperazin-1-il)-etil]-fenil}-pikolinamid (arilpiperazin 6a), dok je N-{3-[2-(4-fenil-piperazin-1-il)-etil]-fenil}-pikolinamid (arilpiperazin 6b) najefikasnije štitio humanu neuroblastomsku ćelijsku liniju SH-SY5Y od 6-OHDA. Arilpiperazin 6a je delimično sprečavao povećanje sadržaja superoksid anjon radikala, smanjenje potencijala membrane mitohondrija i unutarćelijskog sadržaja adenozin-trifosfata (ATP), aktivaciju kaspaza i sledstvenu fragmentaciju DNK koje je izazivao NO. Uočeno smanjenje unutarćelijske koncentracije superoksida nije bilo posledica direktne interakcije ispitivanog arilpiperazina sa O2 -∙, niti je supstanca 6a uticala na akumulaciju NO unutar ćelije. Arilpiperazin 6a je sprečavao inhibiciju protektivnog Akt, kao i aktivaciju proapoptotskih ERK, JNK i AMPK signalnih puteva izazvane SNP-om, ukazujući na bitnu ulogu ovih molekula u njegovom zaštitnom delovanju. Potencijalni značaj arilpiperazina 6a u sprečavanju neurodegenerativnih/neurozapaljenskih procesa posebno naglašava činjenica da je štitio neuronima slične SH-SY5Y ćelije i od citotoksičnog efekta NO-a poreklom od stimulisanih makrofaga. Slično, arilpiperazin 6b je sprečavao povećanje unutarćelijskog sadržaja superoksid anjon radikala (O2 -∙), smanjenje potencijala membrane mitohondrija posledične apoptotske događaje – aktivaciju kaspaza i fragmentaciju DNK – koje je izazivao 6-OHDA. Stabilizacija potencijala mitohondrijalne membrane pod dejstvom arilpiperazina 6b se vremenski poklapala sa smanjenjem unutarćelijskog sadržaja O2 -∙,što ukazuje da je supstanca 6b inhibirala oslobađanje superoksida iz oštećenih mitohondrija stabilizacijom potencijala njihove membrane... We investigated the protective ability of 20 novel arylpiperazine-based dopaminergic ligands against nitric oxide (NO) and dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA)-mediated neurotoxicity. The most potent neuroprotective compound against NO-induced toxicity was N-{4-[2-(4-phenylpiperazin- 1-yl)-ethyl]-phenyl}-picolinamide (arylpiperazine 6a), while N-{3-[2-(4- phenyl-piperazin-1-yl)-ethyl]-phenyl}-picolinamide (arylpiperazine 6b) most effectively protected SH-SY5Y human neuron-like cells from 6-OHDA-generated oxidative injury. Arylpiperazine 6a diminished the proapoptotic action of NO donor sodium nitroprusside (SNP) by decreasing superoxide anion content, mitochondrial membrane depolarization, decline in intracellular adenozine-triphosphate (ATP) content, caspase activation and subsequent phosphatydilserine externalization/DNA fragmentation. The observed decrease of intracellular superoxide concentration was not mediated by direct O2 -∙ scavenging. Arylpiperazine 6a did not interfere with NO accumulation within the cell. The protective effect of arylpiperazine 6a in NO-induced stress was associated with activation of anti-apoptotic (Akt) and the inhibition of proapoptotic (JNK, ERK, AMPK) signaling pathways. A potential therapeutic value of the arylpiperazine 6a in neurodegenerative/neuroinflammatory diseases prevention was additionally supported by the ability of this arylpiperazine to protect SH-SY5Y neuronlike cells from macrophage-derived NO. Similarly, arylpiperazine 6b prevented 6-OHDA-induced increase in superoxide anion content, mitochondrial membrane depolarization and following apoptotic related events – caspase activation and DNA fragmentation. The stabilization of 6-OHDA-disrupted mitochondrial membrane potential by arylpiperazine 6b correlated with the decrease in intracellular superoxide anion (O2 -∙) content, suggesting that decline in O2 -∙ concentration resulted from mitohondrial membrane stabilization Univerzitet u Beogradu Biološki fakultet Anđus, Pavle. 1958- Zogović, Nevena Trajković, Vladimir, 1967- Tomić, Mirko 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=167 https://fedorabg.bg.ac.rs/fedora/get/o:5401/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024560050 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:169 2013-09-30T00:00:00Z 1

Analiza antitumorskog delovanja agenasa modifikovanih azot-monoksidom, Sakvinavir-NO i GIT-27NO na kanceru kolona in vitro i in vivo In vitro and in vivo evaluation of antitumor activity of NO-modified compounds, Saquinavir-NO and GIT-27NO in colon cancer Mojić, Marija S., 1984- Kancer kolona, hemioterapija, GIT-27NO, Saq-NO, apoptoza, metastaze, S6 protein, TRAIL Colon cancer, chemotherapy, GIT-27NO, Saq-NO, apoptosis, metastasis, S6 protein, TRAIL Datum odbrane: 07.03.2013. Iz poznate uzročno-posledične veze infekcije i inflamacije, s jedne strane i karcinogeneze i progresije tumora, s druge strane, proistekla je ideja o upotrebi anti-inflamatornih i anti-infektivnih agenasa u terapiji kancera. Međutim, problem gastrotoksičnosti anti-inflamatornih, kao i generalne toksičnosti anti-viralnih lekova uz činjenicu da je reč o agensima niske biološke iskoristljivosti, ozbiljne su barijere u razmatranju njihove primene u terapiji bolesti za koje inicijalno nisu namenjeni. Kako bi se prevazišla farmakološka ograničenja pomenutih jedinjenja, a imajući u vidu poznato svojstvo azot-monoksida (NO) da neutrališe toksičnost supstanci na različitim nivoima, anti-inflamatornom agensu VGX-1027 i anti-retroviralnom agensu sakvinaviru (Saq) adekvatnom hemijskom intervencijom je dodata grupa dizajnirana da donira NO. Prednost novodobijenih jedinjenja GIT-27NO i Saq-NO nad poznatim nesteroidnim anti-inflamatornim agensima modifikovanim kovalentnim vezivanjem NO (NO-NSAID) je odsustvo molekula “nosača”, koji je inače odgovoran za genotoksičnost NO-NSAID. Strukturna promena ova dva jedinjenja doprinela je njihovom snažnom antitumorskom svojstvu, što je potvđeno brojnim in vitro i in vivo studijama, uz umanjenu toksičnost u slučaju GIT-27NO ili potpunom gubitku toksičnosti Saq-NO tretmana.U ovoj studiji je po prvi put ispitano antitumorsko delovanje GIT-27NO i Saq-NO in vitro i in vivo na modelu kancera kolona, jednog od najtežih formi maligniteta. Kako su oba agensa NO-derivati, definisana je uloga NO u njihovom antitumorskom delovanju. Na molekularnom nivou, determinisani su glavni unutarćelijski događaji pokrenuti u odgovoru na tretman pomenutim jedinjenjima. Na kraju, imajući u vidu značaj mikrosredine za rast i progresiju tumora, ispitana je sposobnost GIT-27NO i Saq-NO da povrate osetljivost ćelija kancera kolona na antitumorski imunski odgovor posredovan TRAIL molekulom. Concept of using anti-inflammatory and anti-infectious agents in cancer therapy is based on a known relationship between inflammation and infection on one side and carcinogenesis and tumor progression on the other side. However, the problem of gastrotoxicity of anti-inflammatory and general toxicity of antiviral drugs, along with their low bioavailability, marks a strong barrier when considering them in therapies for which they were not initially intended for. In order to overcome the pharmacological limits of these compounds, nitric-oxide (NO) with its documented feature to neutralize toxicity of drugs on various levels was added to anti-inflammatory agent VGX-1027 and antiretroviral agent saquinavir (Saq). The advantage of new compounds, GIT-27NO and Saq-NO, over known non-steroid anti-inflammatory agents modified by covalent binding NO moiety (NO-NSAID) is the absence of “carrier” molecule, which is responsible for genotoxicity of NO-NSAID. Structural change in these compounds resulted in potentiation of antitumor action, confirmed by numerous in vitro and in vivo studies, along with reduced toxicity of GIT-27NO or complete loss of toxicity of Saq-NO treatment. In this study, antitumor potential of GIT-27NO and Saq-NO was tested in vitro and in vivo for the first time in colon cancer model, one of the most severe forms of malignancy. As both agents are NO-derivates, the role of NO in their antitumor action was defined. On molecular level, main intercellular events triggered by the treatment were determined. Finally, considering the importance of microenvironment for tumor growth and progression, the ability of GIT-27NO and Saq-NO to re-establish colon cancer cell sensitivity to TRAIL-mediated antitumor immune response was tested. GIT-27NO and Saq-NO reduced the viability of mouse CT26CL25 and human HCT116 colon cancer cell lines, both in vitro and in vivo. The importance of NO release for antitumor action was quite different. While cell viability reduction under GIT-27NO treatment was due to accumulation of high intracellular concentration of NO and consecutively generated oxidative and nitrosative stress, antitumor action of Saq-NO was not mediated by a release of quantitatively relevant amount of this free radical. GIT-27NO induced the accumulation of p53 tumor suppressor, changed pro- and antiapoptotic molecule ratio and triggered mitochondrial membrane depolarization which resulted in cell death via caspase-dependent apoptosis. Univerzitet u Beogradu Biološki fakultet Mijatović, Sanja Mijatović, Sanja. Matić, Gordana Stošić-Grujičić, Stanislava Maksimović-Ivanić, Danijela 2013 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=169 https://fedorabg.bg.ac.rs/fedora/get/o:5402/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024570546 sr Autorstvo-Nekomercijalno-Deliti pod istim uslovima 3.0 Srbija (CC BY-NC-SA 3.0)

oai:eteze.bg.ac.rs:170 2013-09-19T00:00:00Z 1

Ekspresija antioksidativnih enzima i transkripcionog faktora Nrf2 kod pacijentkinja sa benigno, premaligno i maligno transformisanim endometrijumom Expression of antioxidant enzymes and transcription factor Nrf2 in patients with benign, premalignant and malignant endometrial transformation . Todorović, Ana U., 1970- Superoksid dismutaza, katalaza, glutation peroksidaza, glutation reduktaza, Nrf2, kancer endometrijuma, polip, miom, hiperplazija, adenokarciinom Superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, Nrf2, endometrial cancer, polyp, myoma, hyperplasia, adenocarcinoma Datum odbrane: 21.05.2013. Tokom čitavog životnog ciklusa aerobni organizmi su izloženi brojnim endogenim i egzogenim faktorima koji indukuju povećanje produkcije ROS-a. Prisutni u fiziološkim koncentracijama, reaktivni molekuli ROS-a imaju značajnu ulogu u važnim ćelijskim procesima kao što su regulacija signalnih kaskada i genske ekspresije. U visokim koncentracijama ROS mogu oksidovati ćelijske proteine, lipide i DNK i time dovesti do promena strukture i funkcije, oštećenja, pa i smrti ćelije. Kada koncentracija slobodnih radikala premaši fiziološki nivo, smatra se da se ćelija nalazi u stanju oksidativnog stresa. Kako bi sprečili nastanak i umanjili posledice ove vrste stresa, živi organizmi su razvili moćan antioksidativni sistem zaštite (AOS). Ovaj sistem uključuje seriju mehanizama kojima se nivo slobodnih radikala održava u uskom opsegu između fiziološke i toksične koncentracije. Najvažnije enzimske komponente AOS su: superoksid dismutaze (SOD), katalaza (CAT), glutation peroksidaza (GPx) i glutation reduktaza (GR). Ovi enzimi uklanjaju višak ROS-a i učestvuju u održavanju nivoa redukovanog glutationa, čime obezbeđuju očuvanje osnovnih životnih funkcija i sprečavaju nastanak oštećenja i bolesti ćelije. Zbog tako važne uloge AOS, regulacija funkcionalne ekspresije njegovih komponenti je naročito značajna za fiziološke i patološke procese u aerobnim organizmima. Jedan od najvažnijih regulatornih molekula u tom sistemu je Nrf2 (NF-E2 related factor 2). Nrf2 je transkripcioni faktor koji indukuje ekspresiju mnogih citoprotektivnih proteina uključujući i antioksidativne enzime, zbog čega ima značajnu ulogu u regulaciji oksidativnog stresa. Savremena istraživanja na različitim model-sistemima ukazuju na povezanost oksidativnog stresa i kancerogeneze. Razvoj kancera je višestepeni proces koji se razvija kroz tri faze: inicijaciju, promociju i progresiju, a oksidativni stres je povezan sa svakim od ova tri stadijuma transformacije ćelije. Osim toga i sam antioksidativni profil je u ćelijama kancera izmenjen u odnosu na zdrave, normalne ćelije, pa ovi molekuli mogu biti i značajni biomarkeri u dijagnostici, proceni rizika i stepena kancerogeneze... During the life cycle aerobic organisms are exposed to a number of endogenous and exogenous sources of ROS. Present in low to moderate concentrations these reactive molecules play an important role in many physiological processes such as regulation of signaling cascades and gene expression. In high concentrations, ROS can oxidize cellular proteins, lipids and DNA, causing changes in structure and function, damage and even cell death. When the concentration of free radicals exceeds the physiological level, a cell is said to be in a state of oxidative stress. To prevent the onset and reduce the consequences of oxidative stress, living organisms have developed powerful antioxidant system (AOS). This system includes a set of mechanisms to maintain the level of free radicals in the narrow range between physiological and toxic concentrations. The most important enzyme components in AOS are: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR). These enzymes are involved in the removal of ROS and participate in maintaining level of reduced glutathione, thus ensuring the preservation of physiological functions and inhibit the development of cell damage and disease. Because of such an important role of AOS, the regulation of the functional expression of its components is of particular importance for physiological and pathological processes in aerobic organisms. One of the most important regulatory molecules in this system is Nrf2 (NF-E2 related factor 2). Nrf2 is a transcription factor that induces expression of many cytoprotective proteins including antioxidant enzymes, and therefore play an important role in the regulation of oxidative stress. Previous studies have clearly demonstrated a link between oxidative stress and carcinogenesis. Cancer is a multistage process that develops over three stages: initiation, promotion and progression and oxidative stress is associated with each of them. Moreover, antioxidant profile is altered in cancer cells compared with healthy, normal tissue, so these molecules may be important biomarkers in the assessment of risk and the degree of carcinogenesis Univerzitet u Beogradu Biološki fakultet Pejić, Snežana. 1967- Đurašević, Siniša, 1963- Pajović, Snežana B., 1961- Saičić, Zorica S. 2013 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=170 https://fedorabg.bg.ac.rs/fedora/get/o:5404/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024570802 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:171 2013-07-25T00:00:00Z 1

Подизање нивоа квалитета здравствених пословних система Improving quality of health care business systems Živaljević, Aleksandra A., 1974- Здравствени пословни систем, квалитет, модел, анатомска структура, подсистем, процес, параметар квалитета Health care Business system, Quality, Model, Anatomical structure, Subsystem, Process, Quality parameter Datum odbrane: 11.07.2012. Бројне студије спроведене у протеклих двадесет година су показале да упркос примени различитих модела за обезбеђење, управљање или менаџмент квалитетом у организацијама здравствене заштите и даље постоје неусаглашености и грешке, што онемогућава постизање потребног нивоа квалитета ових организација и услуга које оне пружају. Пројектовани и примењени модели за менаџмент квалитетом, управљање квалитетом или обезбеђење квалитета се разликују међу собом, иако су често засновани на истим смерницама, односно стандардима, прописима или концептима, стога они у примени и дају различите резултате. Узроци разлика у структури модела за обезбеђење, управљање или менаџмент квалитетом, као и разликa у резултатима примене ових модела, могу се наћи у процесу превођења смерница у конкретан имплементиран модел за обезбеђење, управљање или менаџмент квалитетом у организацији здравствене заштите, при чему се у конкретном моделу занемарују процеси организације здравствене заштите који нису клинички процеси, али су и даље одговорни за квалитет организације здравствене заштите и квалитет услуга које она пружа. Информације о квалитету различитих лекара или организација здравствене заштите као и о исходима различитих начина лечења или дијагностиковања које су неопходне пацијентима да би се могли смостално опредељивати за одређену организацију здравствене заштите, одређеног лекара или одређен начин лечења и дијагностиковања су често недоступне, недовољне или нису дате у погодном облику за доношење оптималне одлуке... Numerous studies conducted in the last twenty years have shown that in spite of quality models implementation, nonconformities and errors in health care organizations are still present, therefore low quality of those organizations and services they produce is still present, too. These implemented quality models differ among themselves, although they are based on the same guideline, i.e. standard, regulation or concept, so results of implemented models differ as well. The cause of diversity in the structure of implemented quality models and diversity in model results could be found in process of translating guideline into the implemented model for quality assurance or improvement in health care organization, while neglecting processes of health care organization that are not clinical processes, but still responsible for quality of health care organizations and services they produce. Information on the quality of various physician or health care organizations, as well as on the outcomes of different methods of treatment or diagnosis that are necessary for the patients’ appropriation for a particular health care organization, physician, or method of treatment and diagnosis are unavailable, insufficient or not in a suitable form for making the right decision. There is few information available to patients on the quality or outcome of different treatments or different providers or specialists. Health care quality reports are designed primarily to support payers' choice of health plans and quality improvement among plans and providers, not patient awareness and choice. For this reason health care organizations with higher level of quality cannot be awarded with more frequent patients’ appropriation for their services, and patients are not provided with understandable information which would allow them to make a choice based on the factors important to them... Univerzitet u Beogradu Fakultet organizacionih nauka Filipović, Jovan, 1962- Radović, Milić, 1947- Tasić, Ljiljana, 1954- Mijatović, Ivana. 1968- Šantrić-Milićević, Milena, 1968- ( 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=171 https://fedorabg.bg.ac.rs/fedora/get/o:5405/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/515153306 sr Autorstvo-Nekomercijalno 3.0 Srbija (CC BY-NC 3.0)

oai:eteze.bg.ac.rs:173 2013-07-25T00:00:00Z 1

Pristup izgradnji informacionog sistema telekomunikacione kompanije zasnovan na modelima An approach to build information system of telecommunication company based on models Cvetković, Radovan Softverska proizvodna linija, Modeli karakteristika, Višenivovsko fazno konfigurisanje, NGOSS okviri: eTOM i SID, Generisanje modela, Konkretizacija telekomunikacionog domena, Transformacija modela, Biznis i IT poravnanje, Ponovno korišćenje softvera, Metodologija razvoja IS Software Product Line, Feature Models, Multilevel Staged Configuration, NGOSS Frameworks: eTOM and SID, Model Generation, Concretization of telecommunication domain, Model Transformation, Business and IT Alignment, Software Reuse, IS Development Methodology. Datum odbrane: 15.10.2012. U ovom radu se definiše metodološki pristup za izgradnju informacionog sistema telekomunikacione kompanije zasnovan na modelima objedinjavanjem opštih pristupa razvoja IS i specifične inicijative u oblasti telekomunikacija:  MDA (Model Driven Architecture), pristup razvoju softvera koji je kao standard utvrdila i promoviše OMG (Object Management Group).  EA (Enterprise Architecture), pristup za razvoj arhitekture preduzeća, razvoj poslovanja i IT-a istovremeno. TOGAF (The Open Group Architectural Framework) je opšti najpoznatiji arhitekturalni okvir i metod za razvoj arhitekture preduzeća.  NGOSS (The New Generation Operations Systems and Software) program koji razvija Telemanagement Forum i koji predstavlja okvir za razvoj i primenu „Operation and Business Support Systems – OSS/BSS“ u telekomunikacionoj industriji.  SPL (Software Product Line), razvoj IS preko Softverskih proizvodnih linija, predstavlja savremeni pristup za automatizaciju razvoja softvera koji je zasnovan na domenskim, specifičnim modelima gde se kroz domensko inženjerstvo razvija familija softverskih proizvoda a ne pojedinačni softverski proizvod. Osnovu metodološkog pristupa čini specifična softverska proizvodna linija za telekomunikacioni domen koja je zasnovana na NGOSS okvirima i modelima i omogućava efikasnu izgradnju IS telekomunikacione kompanije kroz tri posebna procesa:  Opšti domenski inženjering telekomunikacionog domena,  Domenski inženjering telekomunikacionog domena za tip servisa,  Aplikacioni inženjering... This work gives definition of a methodological approach to build information system of telecommunication company based on models, through consolidation of general approaches of IS development and a specific initiative within telecommunication area:  MDA (Model Driven Architecture), an approach to software development that was set as a standard and promoted by OMG (Object Management Group).  EA (Enterprise Architecture), an approach to simultaneous development of Business and IT Architecture of a company. TOGAF (The Open Group Architectural Framework) is the most common and best known architecture framework and method for enterprise architecture development.  NGOSS (New Generation Operations Systems and Software), a program being developed by Telemanagement Forum that represents a framework for development and implementation of „Operation and Business Support Systems – OSS/BSS” within telecommunication industry.  SPL (Software Product Line), a development of IS over Software Product Lines, represents a modern approach to automation of domain-specific model-driven software development, where a software product family, and not a single software product, is developed through domain engineering. The methodological approach is based on a software product line specific to telecommunication domain which is based on NGOSS frameworks and models and which allows efficient building of Telecommunication Company IS through the following three distinct processes:  General domain engineering for telecommunication domain,  Domain engineering for telecommunication domain type of service,  Application engineering... Univerzitet u Beogradu Fakultet organizacionih nauka Marjanović, Zoran. 1960- Nešković, Siniša. 1962- Dukić, Miroslav. 1949- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=173 https://fedorabg.bg.ac.rs/fedora/get/o:5407/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/515303578 sr Autorstvo-Nekomercijalno 3.0 Srbija (CC BY-NC 3.0)

oai:eteze.bg.ac.rs:174 2013-07-26T00:00:00Z 1

Model IT infrastrukture za e-obrazovanje IT infrastructure model for e-learning Vujin, Vladimir Elektronsko obrazovanje, IT Infrastruktura, Cloud Computing e-learning, it infrastructure, Cloud Computing Datum odbrane: 09.05.2012. Elektronsko obrazovanje je kompleksan sistem koji uključuje učenje na daljinu, predavanja na daljinu, nastavne materijale u raznim elektronskim formama, individualni i grupni proces učenja, tutorski i interaktivni rad. Ogroman i brzi rast broja korisnika, usluga, obrazovnih sadržaja i potrebnih resursa, suočavaju obrazovne ustanove i njihove sisteme elektronskog obrazovanja sa izazovima optimizacije izdvajanja resursa, zahtevima dinamičke konkurentnosti i sa kontrolom troškova ovakvih sistema. Sve ovo dovodi do toga da su zahtevi za projektovanje i implementaciju IT infrastrukture sistema za elektronsko obrazovanje sve kompleksniji. Primenom savremenih informaciono-komunikacionih tehnologija moguće je doprineti povećanju efikasnosti, fleksibilnosti i ekonomičnosti sistema za elektronsko obrazovanje. Uvođenjem modela IT infrastrukture za elektronsko obrazovanje, zasnovanog na savremenom IT konceptu Cloud Computing-a, mogu se unaprediti obrazovni procesi sa stanovišta pouzdanosti, skalabilnosti i ekonomičnosti sistema. Nedovoljno razvijena naučna podrška primene koncepta Cloud Computing-a u modelovanju IT infrastrukture u visokoškolskom obrazovanju Republike Srbije i strateška važnost ovog koncepta, ukazuje na potrebu postavljanja teorijske podrške njegovog efikasnijeg razvoja i primene. U tom smislu je i predstavljen predmet istraživanja disertacije, koji se bazira na definisanju i razvijanju planova i aktivnosti visokoškolskih ustanova, vezanih za razvoj modela IT infrastrukture za elektronsko obrazovanje pomoću Cloud Computing koncepta. Preispitujući postojeće i tražeći nove načine pružanja usluga studentima i naučno-istraživačkom osoblju, visokoškolske ustanove se suočavaju sa velikim brojem izazova uglavnom oko digitalnog identiteta i upravljanja pristupom. Prvi i možda najveći izazov je kako da se podstakne usvajanje i implementacija sistema za upravljanje digitalnim identitetom. Uspešna IT infrastruktura za upravljanje digitalnim identitetom zahteva celovito razmišljanje o identitetima i međuzavisnostima koje između njih postoje. Drugi izazov je izgradnja podrške za sistem koji će moći da iskoristi sve prednosti saveza sistema za upravljanje digitalnim identitetima. Stvaranjem ovakvih saveza između obrazovnih ustanova obezbeđuje se mobilnost korisnika, sadržaja i usluga. Glavna hipoteza koja je razvijena i dokazana u okviru doktorske disertacije je da se primenom razvijenog modela IT infrastrukture može uticati na efikasnost i ekonomičnost sistema za elektronsko obrazovanje. U eksperimentalnom delu doktorske disertacije realizovano je istraživanje usmereno ka validaciji predloženog modela IT infrastrukture za elektronsko obrazovanje... E-learning is a complex system which includes distance learning, lectures, and classroom materials in various electronic forms; both individual and group learning process, tutor and interactive work. A significant and rapid increase in the number of users, services, educational content and resources required, face educational institutions and their e-learning systems with new challenges of optimization of singling resources out, with the demands of dynamic competitiveness and with the control of expenses of such systems. All this leads to the fact that the demands for development and implementation of IT infrastructure for e-learning systems are becoming more complex. By applying modern information and communication technologies, it is possible to increase efficiency, flexibility and cost-effectiveness of e-learning systems. Through introducing models of IT infrastructure for e-learning based on a contemporary IT concept of Cloud Computing, the reliability, scalability and cost-effectiveness of a system of educational processes could be improved. Insufficient development of scientific support in the application of the Cloud Computing concept in modeling the IT infrastructure of higher education of the Republic of Serbia and the strategic importance of this concept indicates the need to establish theoretic support for its more efficient development and application. With regards to this, the subject of the dissertation research is presented, based on defining and development of plans and activities of higher education institutions, related to the development of IT infrastructure model for e-learning by means of Cloud Computing concept. Through examining the existing and searching for new ways of providing services to students and scientific research staff, higher education institutions are faced with a significant number of challenges, mainly regarding digital identity and access management. The first and probably the greatest challenge is to prompt adoption and implementation of digital identity management systems. Successful IT infrastructure for digital identity management requires systematic thinking about identities and interdependence which exists between them. The second challenge is to provide support for a system which would be able to use all advantages of federation systems for digital identities management. The development of such federations among educational institutions enables mobility of users, content and services. The main hypothesis devised and proven within the doctoral thesis is that the application of a developed IT infrastructure model can influence the efficiency and cost-effectiveness of e-learning systems. The experimental part of the doctoral thesis is consisted of a research, directed towards the validation of the proposed IT infrastructure model for e-learning... Univerzitet u Beogradu Fakultet organizacionih nauka Radenković, Božidar. 1958- Zrakić, Marijana Despotović- Stanojević, Milorad, 1947- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=174 https://fedorabg.bg.ac.rs/fedora/get/o:5408/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/515130266 sr Autorstvo-Deliti pod istim uslovima 3.0 Srbija (CC BY-SA 3.0)

oai:eteze.bg.ac.rs:176 2013-09-30T00:00:00Z 1

Модел B2B интеграције саобраћајних пословних система A model for B2B integration traffic systems Janković, Slađana, 1978- B2B Integration, Interoperability of Traffic Systems, Cloud Computing, SOA Датум одбране: 20.07.2012. The subject of this dissertation is to define a methodology and a model of interoperable e-business of the traffic business systems based on their B2B (Business to Business) integration in the cloud computing technology environment. The survey was adapted for use in transportation businesses in Serbia. Traffic and transportation systems are heterogeneous systems that share information in their operation. Some of the causes of non-interoperable e-business can be found in the fact that transportation business systems develop, maintain and update databases that are relevant for other traffic systems; in the databases that they use, the same entities are modeled from the real system, using different methodologies and tools; update own database by downloading information from the databases of other transportation business systems; due to the inability to exchange data at the level of information systems, they download the data manually, which causes a delay in updating the data; maintain and update the entire databases that are not relevant to them in order to occasionally generate statistical reports; making business decisions about common issues based on syntactically and semantically incompatible reports. The literature often describes four types of B2B integration: information integration, user interface-based integration – portal integration, business process integration and integration of services. In this dissertation we perform the analyzes the existing and development of the new models of B2B integration of traffic business systems based on combining the four listed types of integration. Service-oriented architecture (SOA) of the traffic and transport information systems provides interoperability at the application level and the level of business processes, while at the semantic level interoperability is provided by creating a common domain ontology and development of a common data model based on the domain ontology. SOA and integration of the traffic and transportation applications is implemented by development and use of WCF Data Services (Windows Communication Foundation Data Services) hosted on the cloud computing platform. Model for exchange of information and services that are proposed in this dissertation is based on combining the three models of service delivery from the cloud: Infrastructureas- a-Service, Platform-as-a-service and Software-as-a-service. Development and hosting of a shared database in the cloud, the infrastructure and platform are using as a service, and developing and hosting applications in the cloud are using the platform and software as a service. Implementation of the proposed model consists of development of a Web portal and SQL Azure database in the cloud. The portal provides users with traffic and transportation related applications and informations from the SQL Azure database. Existing applications in the traffic and transportation organizations are addressing WCF Data services from the cloud. By applying the proposed solution, there will be no need for updating and maintaining related databases on the servers of different organizations. Consequently that would reduce the redundancy and ensure the data integrity. . Univerzitet u Beogradu Fakultet organizacionih nauka Radenković, Božidar. 1958- Zrakić, Marijana Despotović- Stanojević, Milorad, 1947- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=176 https://fedorabg.bg.ac.rs/fedora/get/o:5410/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/515165082 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:177 2013-07-26T00:00:00Z 1

Primena fazi logike u analizi funkcionalnih zavisnosti u relacionim bazama podataka Analysis of functional dependencies in relational databases using fuzzy logic Vučetić, Miljan fazi relacija, fazi funkcionalna zavisnost, fazi implikacija, rudarenje podataka fuzzy relation, fuzzy functional dependency, fuzzy implication Datum odbrane: 1.06.2013. Predmet istraživanja u disertaciji su fazi funkcionalne zavisnosti u relacionim bazama podataka, a cilj istraživanja je proučavanja dosadašnjih rezultata u ovom polju, te razvoj sopstvenog algoritma za identifikovanje zavisnosti između atributa relacije koji je zasnovan na primeni fazi implikacija iz fazi logike. Problem analize fazi funkcionalnih zavisnoti nije nov. U ovoj oblasti postoji značajan broj radova u poslednje dve decenije i veliki broj autora se bavio ovom problematikom. Međutim, analizom dostupne literature utvrđeno je da ne postoji algoritam koji bi omogućio identifikovanje zavisnosti između atributa relacione šeme. Ovo ograničenje bilo je motiv za razvoj sopstvenog pristupa u analizu funkcionalnih zavisnosti nad datim skupom atributa. Rešavanje ovog, ne tako novog problema, ne predstavlja samo teorijski značaj i istraživački izazov, već ima i praktični značaj. U tom smislu, cilj istraživanja je implementacija logičkog modela baze podataka koju daje prethodna teorija i koja podržava očekivane rezultate istraživanja, ali i veza sa drugim oblastima i poljima (geografski informacioni sistemi, rudarenje podataka, ekstrakcija informacija, smanjenje redundancije, estimacija nepoznatih vrednosti atributa...). Polazna pretpostavka je bila da teorija fazi skupova i određeni fragment fazi logike predstavljaju pogodno rešenje kada projektanti informacionih sistema ne mogu jednoznačno da odrede zavisnost između podataka i atributa relacije. U oblasti veštačke inteligencije, fazi skupovi i fazi logika izučavaju se sa aspekta dizajniranja fazi ralacionih baza podataka, u okviru inteligentnih sistema, jer teorija fazi skupova i fazi logika predstavljaju moćan alat za manilupisanje nepreciznim i neodređenim informacijama. Otkrivanje potencijalnih zavisnosti između atributa posmatrane fazi relacije ustvari predstavlja pronalaženje skrivenih i korisnih znanja koja možemo da koristimo za donošenje poslovnih i upravljačkih odluka. U radu je predstavljena nova tehnika koja identifikuje postojanje zavisnosti između atributa na nivou podrelacije (parova n-torki) primenom različitih fazi implikacija, čija karakterizacija je opisana u ovoj disertaciji u kontkestu primene u ovoj problematici. Fazi implikacije koje zadovoljavaju ustanovljene kriterijume prihvatanja koristimo za procenu jačine zavisnosti θ u slučaju postojanja fazi funkcionalne zavisnosti X   Y. Za potrebe demonstracije predložene metodologije i verifikaciju rezultata istraživanja izvršen je eksperiment nad realnim podacima u fazi modelu baze podataka na bazi relacije bliskosti i fazi modelu na bazi mogućnosti distribucije. Da bismo identifikovali fazi funkcionalne zavisnosti u odgovarajućem fazi modelu potrebno je: 1. Pripremiti podatke za analizu, 2. Pronaći podrelacije (parove n-torki) na posmatranim atributima u kojima se potencijalno kriju fazi funkcionalne zavisnosti, 3. Pridružiti fazi funkcionalnim zavisnostima odgovarajuće fazi implikacije, 4. Interpretirati rezultate istraživanja da bismo dobili konačan skup fazi zavisnosti... The research presented in this dissertation is finding of fuzzy functional dependencies in the fuzzy relational database models. The goal is reviewing and analyzing of recent results in this field and developing our own algorithm for identification of dependencies between attributes in the fuzzy relations based on fuzzy implication in fuzzy logic. The problem of fuzzy functional dependency analzsing in fuzzy relational database models is not recent. In this area there is a significant number of papers and authors dealt with mentioned issue in the last two decades. However, literature analysis showed that there is no algorithm that would enable the identification of attribute relationships in relational schemas. This restriction was the motive for the development of our metodology in the analysis of fuzzy functional dependencies over a given set of attributes. Solving this, not so new problem, is not only research challenge having theoretical importance, but it also has practical significance. Implementation of logical database models provided by the previous theory and integration to other areas and fields (GIS, Rudarenje podataka, Information Retrieval, reducing data redundansy,estimation of NULL values...) are crucial aims in this paper. The initial assumption was that the theory of fuzzy sets and particular fragment of fuzzy logic are the perfect solution when database managers can’t unambiguously determine the relationships between data and attributes within the relation. In the field of artificial intelligence, fuzzy sets and fuzzy logic are studied in terms of fuzzy relational database design within the intelligent systems because fuzzy set theory and fuzzy logic are powerful tools for manipulating and representing imprecise and uncertain information. Finding potential dependencies between attributes in fuzzy relations is actually rudarenje podataka technique related to hidden and useful knowledge used for decision making. This dissertation presents a new technique for identification of existing dependencies between pairs of tuples using different fuzzy implications which characterization is described by author. Fuzzy implications meeting established acceptance criteria are used for estimation of linguistic strength θ when fuzzy functional dependency X   Y is satisfied. For demonstration of proposed methodology and research verification we performed experiment on real data under two different models: fuzzy database model based on proximity relation and fuzzy database model with possibility distribution. Discovering potential dependencies between attributes of the observed fuzzy relation actually represents a discovery of hidden and useful knowledge, i.e. a rudarenje podataka technique. In order to identify fuzzy functional dependency within the corresponding fuzzy model, following is necessary: 1. Preparing the data for the analysis (preprocessing, data summarization, data warehousing etc.). 2. Finding subrelations (n-tuples) on the observed attributes with potentially hidden fuzzy functional dependencies. 3. Associating fuzzy functional dependencies with corresponding fuzzy implications. 6 4. Interpreting search results for the purpose of getting the final set of fuzzy dependencies... Univerzitet u Beogradu Fakultet organizacionih nauka Vujošević, Mirko, 1952- Aničić, Nenad. 1970- Avramović, Zoran Babarogić, Slađan, 1970- Radojević, Dragan 2013 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=177 https://fedorabg.bg.ac.rs/fedora/get/o:5411/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/515339418 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:178 2013-09-30T00:00:00Z 1

Tunelovanje elektromagnetskih talasa kroz kompleksne optičke sredine Tunneling of electromagnetic waves through complex optical media Ilić, Igor, 1984- elektromagnetno tunelovanje, nelinearna optika, metamaterijali electromagnetic tunneling, nonlinear optics, metamaterials Datum odbrane: 15.03.2012. Predmet ove disertacije je analiza karakteristika tunelovanja elektromagnetskih talasa kroz različite kompleksne optičke sredine, sa posebnim osvrtom na metamaterijale sa negativnim indeksom prelamanja. Teorijski su razmatrane različite strukture, te su za njih, korišdenjem brojnih matematičkih metoda, izvedeni izrazi za vremena tunelovanja u: (1) nelinearnim disperzivnim anizotropnim strukturama, (2) linearnim anizotropnim strukturama (poluprovodničkim metamaterijalima), a proračunat je i uticaj Gus-Henkenovog pomeraja na ova vremena. Vremena tunelovanja za različite, postojede, strukture su izračunate koridenjem numeričke metode pod nazivom metoda pogađanja (shooting method), koja je odgovarajuda za ovu problematiku. Takođe, teorijski je razmatrana propagacija elektromagnetnog zračenja u anizotropnim strukturama sastavljenim od naizmenično postavljenih slojeva dva različita poluprovodnika, te je, na osnovu ove analize, dizajniran poluprovodnički metamaterijal sastavljen od naizmenično postavljenih slojeva različito dopiranih InGaAs. Mogudnost negativnog prelamanja u ovim materijalima potvrđena je primenom FDTD (Finite-Difference Time-Domain) numeričke metode, koja omogudava simulaciju realnog prostiranja elektromagnetnog zračenja kroz različite strukture. Subject of this dissertation is the analysis of electromagnetic waves tunneling properties through different complex optical media, with emphasis on metamaterials with negative index of refraction. Different structures are theoretically considered, i.e., using numerous mathematical methods, expressions for tunneling times are derived for: (1) nonlinear dispersive anisotropic structures, (2) linear anisotropic structures (semiconductor metamaterials). Also, influence of Goos- Hänchen shift on these times is calculated. Tunneling times for existing structures are calculated by using suitable numerical method: shooting method. Besides these, propagation of electromagnetic radiation through anisotropic structures composed of alernately placed layers of two different semiconductors is analyzed. On the grounds of this analysis, semiconductor metamaterial composed of alternately placed layers of differently doped InGaAs is designed. The possibility of obtaining negative refraction in these structures is confirmed by using FDTD (Finite-Difference-Time-Domain) numerical method, which enables simulation of electromagnetic radiation propagation through various structures. Univerzitet u Beogradu Elektrotehnički fakultet Radovanović, Jelena, 1973- Hadžievski, Ljupčo, 1957- Milanović, Vitomir, 1947- Petrović, Jovana, 1978- Radunović, Jovan, 1949- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=178 https://fedorabg.bg.ac.rs/fedora/get/o:5414/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/43479567 sr Autorstvo-Nekomercijalno 3.0 Srbija (CC BY-NC 3.0)

oai:eteze.bg.ac.rs:179 2013-07-29T00:00:00Z 1

Model za procenu efikasnosti izbora tehnologija digitalne televizije Simulation model for digital broadcasting technologies efficiency estimation Sugaris, Aleksandar DVB-T, DVB-T2, MPEGx, digitalna dividenda, tehno-ekonomska analiza, modeliranje, strateško planiranje, efikasnost tehnologija, PayTV, Bass difuzioni model DVB-T, DVB-T2, MPEGx, digital dividend, techno-economic analysis, modeling, strategic planning, technology efficiency, PayTV, Bass diffusion model Datum odbrane: 5.07.2012. Digitalizacija zemaljskog emitovanja televizijskih programa prva je velika promena u TV sistemima još od uvoĊenja kolor televizije. Prelazak sa analognog na digitalno emitovanje predstavlja jedan od najvećih izazova u razvoju video i audio tehnologije i desiće se u celom svetu u veoma bliskoj budućnosti. Pored ozbiljnih tehniĉkih zahvata, ovaj proces zahteva znaĉajne finansijske investicije vezane za enorman broj standardnih TV prijemnika i široko rasprostranjene televizijske mreţe. Zbog toga, gde god je moguće u distributivnoj mreţi, potrebno je obezbediti kompatibilnost sa postojećim sistemima. Nasuprot tome, digitalizacija video signala visoke rezolucije zahteva visoko sofisticirane algoritme sa velikom kompresijom i veoma efikasnom tehnologijom prenosa. Trenutno u svetu koriste se tri meĊunarodna standarda za digitalno zemaljsko emitovanje TV programa - Advanced Television Systems Committee (ATSC) u upotrebi u Severnoj Americi i Juţnoj Koreji, Digital Video Broadcasting Terrestrial (DVB-T) pored Evrope upotrebljava se u Australiji, Indiji i nekim zemljama Azije i Afrike, Integrated Services Digital Broadcasting Terrestrial (ISDB-T), koristi se u Japanu i Juţnoj Americi. Fokus ove disertacije je na analizi performansi i razvoju metoda za procenu efikasnosti tehnologija za fiksni prijem koje se koriste u Evropi. Za isporuku TV servisa krajnjim korisnicima postoje tri glavna sistema prenosa, satelitski, kablovski i preko zemaljskih predajnika. Digitalni zemaljski sistem je sposoban za isporuku TV programa ĉak i mobilnim korisnicima. Servisi prenosa podataka i televizije visoke rezolucije (HD) raspoloţivi su preko digitalnih satelitskih i kablovskih mreţa, ali sve do sada korisnici zemaljskih mreţa nisu primali ove servise jer je za njihov prenos potreban veći kapacitet kanala u odnosu na onaj korišćen za televiziju standardne rezolucije (SD) - Digital Video Broadcasting Terrestrial (DVB-T) i Moving Picture Expert Group MPEG-2 standard kompresije. Novije tehnologije, kao što su standard kompresije MPEG-4 verzija 10 i druga generacija standarda za zemaljsko emitovanje (DVB-T2), obezbeĊuju povećan kapacitet i robusnost u zemaljskim mreţama. MeĊutim, pored tehniĉkih prednosti evidentno je da najnovije tehnologije sa sobom donose i više cene opreme i sistema. Sprovodljivost poslovnog plana uvoĊenja digitalnog emitovanja je pod direktnim uticajem ovih tehno-ekonomskih pitanja. The first major change within the TV system since the introduction of color is the digitalization of television terrestrial broadcast network. The digital switchover is one of the main challenges in video and audio technology developments and it is going to happen in the very near future throughout the world. Besides the severe technical requirements, this process is driven by significant financial investments, regarding to an enormous number of standard TV sets and widespread broadcast networks. Consequently, it is necessary, wherever is possible in distribution network, to ensure the compatibility with existing systems. On the contrary, digitization of high-resolution video and audio signals needs highly sophisticated algorithms with high compression and very efficient transmission technology. There are three international standards currently used world-wide for digital terrestrial broadcasting - Advanced Television Systems Committee (ATSC) used in North America and South Korea, Digital Video Broadcasting Terrestrial (DVB-T) used apart from Europe in Australia, India and some other Asian and African countries, Integrated Services Digital Broadcasting Terrestrial (ISDB-T), used in Japan and South America. The focus of this dissertation is the performance analysis and efficiency estimation method applied to the technologies for fixed reception used in our region – Europe. The three main transmission systems for delivering TV service to end-users are satellite, cable and terrestrial networks. The digital terrestrial television (DTT) system is capable of distribution of television content even to the mobile devices. Data-casting services and high-definition (HD) television content is available via digital satellite and digital cable networks but, until now, terrestrial users have not received data and HD content because its transmission requires a higher channel capacity than that used for standard definition (SD) TV - Digital Video Broadcasting Terrestrial (DVB-T) and Moving Picture Expert Group MPEG-2 coding and compression standard. The latest technologies, like compression standard MPEG-4 part 10 and the second generation of digital terrestrial broadcasting standard (DVB-T2), provide increased capacity and ruggedness in the terrestrial transmission networks. But besides technical benefits it is evident that the latest technologies bring also a higher system cost. The viability of digital broadcasting business case is directly influenced by this techno-economic issue. Univerzitet u Beogradu Elektrotehnički fakultet Reljin, Irini, 1952- Dukić, Miroslav, 1949- Reljin, Branimir, 1945- Samčović, Andreja, 1963- Bjelica, Milan, 1977- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=179 https://fedorabg.bg.ac.rs/fedora/get/o:5415/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/43464207 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:184 2013-07-31T00:00:00Z 1

Modelovanje gradiranih fotonskih plazmonskih kristala koji rade u režimu metamaterijala Modelling of graded photonic and plasmonic crystals in metamaterial regime Vasić, Borislav fotonski i plazmonski kristali, elektromagnetski metamaterijali, novi plazmonski materijali - grafen photonic and plasmonic crystals, electromagnetic metamaterials, new plasmonic materials - graphene Datum odbrane: 27.12.2012. U ovoj tezi su istraˇzeni elektromagnetski kompozitni materijali u cilju realizacije sredina sa elektromagnetskim osobinama koje ne postoje u prirodnim materijalima. Istraˇzivani kompoziti su jednodimenzionalni i dvodimenzionalni fotonski i plazmonski kristali. Jednodimenzionalne strukture se sastoje od slojeva odgovaraju´ceg oblika, dok se dvodimenzionalne strukture sastoje od ˇstapi´ca u vazduhu ili cilindriˇcnih rupa u dielektriku. Pored struktura sa periodiˇcnim ponavljanjem jediniˇcnih ´celija, razmatraju se i gradirane strukture dobijene prostornom promenom geometrije ili dielektriˇcne permitivnosti jediniˇcnih ´celija. Fotonski kristali se sastoje iskljuˇcivo od dielektrika, dok su plazmonski kristali kombinacija dielektriˇcnih i plazmonskih materijala, metala ili poluprovodnika. Posebna klasa razmotrenih kompozitnih struktura su planarni plazmonski kristali koji se sastoje od paralelnih traka od plazmonskih materijala na dielektriˇcnom substratu. Sve kompozitne strukture se razmatraju u reˇzimu metamaterijala gde veliˇcina jedini ˇcne ´celije nije zanemarljiva u odnosu na talasnu duˇzinu svetlosti, ali se efektivni parametri ipak mogu definisati. I jednodimenzionalne i dvodimenzionalne strukture su homogenizovane pomo´cu Maksvel Garnetove teorije. Planarni plazmonski kristali nisu opisani efektivnim parametrima, nego se razmatraju kao nizovi istih i podtalasnih rezonatora sa definisanim plazmonskim rezonancijama tako da rezonantne karakteristike plazmonskih kristala predstavljaju kolektivni odziv svih rezonatora. Posebna paˇznja je posve´cena izboru odgovaraju´cih materijala u kompozitima. Strukture namenjene vodenju elektromagnetskog polja treba da imaju ˇsto manje gubitke tako da u ovom sluˇcaju strukture treba da budu iskljuˇcivo dielektriˇcne. Plazmonski materijali kao ˇsto su metali i poluprovodnici se moraju koristiti u slede´cim sluˇcajevima: u realizaciji visoke anizotropije dielektriˇcne permitivnosti i u realizaciji rezonantnih struktura. Prvi metod koji je istraˇzivan za vodenje elektromagnetskog polja je transformaciona optika. U ovom metodu, prave linije polja u slobodnom prostoru se na odgovaraju´ci naˇcin transformiˇsu u linije polja sa ˇzeljenim oblikom. Maksvelove jednaˇcine su invarijantne prilikom koordinatnih transformacija dok se materijalni parametri menjaju u skladu sa primenjenom transformacijom. Dobijeni materijalni parametri su opisani anizotropnom i prostorno nehomogenom dielektriˇcnom permitivno ˇs´cu i magnetskom peremabilnoˇs´cu u opˇstem sluˇcaju. Ovde je data procedura kojom se nalaze jednostavniji materijalni parametri pomo´cu koncepta redukovanih parametara pri ˇcemu se zadrˇzava ista disperzija ili pomo´cu koncepta transformacija sa jediniˇcnim Jakobijanom. Kao rezultat primenjenih procedura, pokazuje se da je mogu´ce realizovati uredaje na bazi transformacione optike pomo´cu anizotropne i prostorno nehomogene dielektriˇcne permitivnosti. Anizotropija je onda realizovana slojevima ploˇca, dok se nehomogenost moˇze realizovati odgovaraju´com gradacijom debljine ili permitivnosti ploˇca.parametri menjaju u skladu sa primenjenom transformacijom. Dobijeni materijalni parametri su opisani anizotropnom i prostorno nehomogenom dielektriˇcnom permitivno ˇs´cu i magnetskom peremabilnoˇs´cu u opˇstem sluˇcaju. Ovde je data procedura kojom se nalaze jednostavniji materijalni parametri pomo´cu koncepta redukovanih parametara pri ˇcemu se zadrˇzava ista disperzija ili pomo´cu koncepta transformacija sa jediniˇcnim Jakobijanom. Kao rezultat primenjenih procedura, pokazuje se da je mogu´ce realizovati uredaje na bazi transformacione optike pomo´cu anizotropne i prostorno nehomogene dielektriˇcne permitivnosti. Anizotropija je onda realizovana slojevima ploˇca, dok se nehomogenost moˇze realizovati odgovaraju´com gradacijom debljine ili permitivnosti ploˇca.parametri menjaju u skladu sa primenjenom transformacijom. Dobijeni materijalni parametri su opisani anizotropnom i prostorno nehomogenom dielektriˇcnom permitivno ˇs´cu i magnetskom peremabilnoˇs´cu u opˇstem sluˇcaju. Ovde je data procedura kojom se nalaze jednostavniji materijalni parametri pomo´cu koncepta redukovanih parametara pri ˇcemu se zadrˇzava ista disperzija ili pomo´cu koncepta transformacija sa jediniˇcnim Jakobijanom. Kao rezultat primenjenih procedura, pokazuje se da je mogu´ce realizovati uredaje na bazi transformacione optike pomo´cu anizotrparametri menjaju u skladu sa primenjenom transformacijom. Dobijeni materijalni parametri su opisani anizotropnom i prostorno nehomogenom dielektriˇcnom permitivnoˇs´cu i magnetskom peremabilnoˇs´cu u opˇstem sluˇcaju... In this thesis we investigate electromagnetic composite materials in order to realize media with the electromagnetic properties not achievable in the nature. The investigated composites are one dimensional and two dimensional photonic and plasmonic crystals. One dimensional structures consist of appropriately shaped slabs, whereas two dimensional structures consist of rods in air or cylindrical holes in a dielectric host. Beside the structures with the periodic arrangement of the unit cells, we consider graded structures obtained by a spatial variation of either cells’ geometry or dielectric permittivity. Photonic crystals are all dielectric structures whereas the plasmonic crystals are combination of dielectric and plasmonic materials, metals or semiconductors. Special class of the composite structures are the planar plasmonic crystals which consist of parallel ribbons made from plasmonic material on a dielectric substrate. All composites are considered in the metamaterial regime where unit cell size of the composites are not negligible in comparison to light wavelength, but the effective parameters can be still well defined. Homogenization of both one and two dimensional structures are done within the framework of Maxwell Garnett theory. Planar plasmonic crystals are not described by effective parameters, but they are considered as arrays of the same and subwavelength resonators with well defined plasmonic resonances so the resonant behaviour of the plasmonic crystals is the collective response of all resonators. Special attention is devoted to the choice of appropriate materials in the composites. The structures aimed for guiding of electromagnetic field should have as low as possible losses so the structures built form dielectrics only are the most preferably in this case. The plasmonic materials such as metals or semiconductors have to be used in the following cases: in the realization of extreme anisotropy in the dielectric permittivity and in the realization of resonant structures. The first method investigated for guiding of electromagnetic field is transformation optics. In this method, straight field trajectories in free space are appropriately transformed into the desired field trajectories. Maxwell equations are invariant under the applied coordinate transformations while the material parameters are scaled accordingly. The obtained material parameters are described with anisotropic and spatially inhomogeneous dielectric permittivity and magnetic permeability in a general case... Univerzitet u Beogradu Elektrotehnički fakultet Gajić, Radoš Radovanović, Jelena Tadić, Milan, 1964- Milanović, Vitomir, 1947- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=184 https://fedorabg.bg.ac.rs/fedora/get/o:5428/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/43465487 sr Autorstvo-Deliti pod istim uslovima 3.0 Srbija (CC BY-SA 3.0)

oai:eteze.bg.ac.rs:186 2013-08-01T00:00:00Z 1

Планирање предела као инструмент просторног развоја Србије Landscape planning as an instrument of spatial development of Serbia Vasiljević, Nevena B., 1965- Планирање предела, теорије и модели планирања предела, планирање за предео, планирање кроз предео, карактер предела као јавно добро, институционализација планирања предела у систем просторног планирања у Србији Landscape planning, theories and models of landscape planning, planning for landscape, planning through landscape, landscape character as a public benefit, institutionalization of the landscape planning in the system of spatial planning in Serbia Datum odbrane: 19.03.2013. Проблем дефинисања основе на којој се гради концепт планирања предела као инструмента просторног развоја Србије је централно питање којим се аутор бави у овом раду. Да идеје на којима почива постојеће планирање предела (у Србији посебно) више нису идеје времена у ком живимо, основна је теза која је покренула ово истраживање. Глобални процеси су створили нови амбијент у ком се данас планира: планирање за предео је превазиђено. Данашња теоријска парадигма мења тежиште, односно просторни концепт. Предео није више само резерват културне и природне баштине који треба конзервирати у затеченој слици, већ је холистички, хибридни, ентитет природних, културних и социјалних вредности који се мења и развија. Као такав он постаје предмет истраживања. Овим радом су понуђени елементи за грађу другачијег концепта планирања - планирања кроз предео. Настао је као модел примене нове парадигме којом су дефинисани просторни концепт и планерски принципи. Парадигма интегрише научнe принципe: предеоне екологије, естетике предела као система и принципе комуникативног планирања у оквирима предела (као просторног концепта). У хеуристичком смислу, обједињена је дескриптивна и прескриптивна теорија планирања, а решавање научних проблема и задатака заснива се на: концепту предела као целине, трансдисциплинарности у истраживачком приступу и карактеру предела као новој вредности (јавно добро)у систему планирања. У интерпретацији новог концепта планирања, питања просторног развоја воде ка опредељењу за тип односно карактер будућег предела, који је јавно добро и јавни интерес, у који су уграђени циљеви свих сектора (становања, индустрије, пољопривреде, шумарства, енергетике, заштите животне средине, природног и културног наслеђа...). Степен интегративности и холизма нас може определити у закључку да се понуђени односно могући концепт умногоме разликује од постојећег. А да ли је и основа за планирање бољих и лепших предела питање је непредвидљивости будућег развоја планирања уопште. С обзиром на искуства вечите потраге за моделом интегралног планирања, као и неизвесности у ком се планирање креће, отворена су нова питања и дилеме... The problem of defining the basis to the concept of landscape planning as an instrument of spatial development in Serbia is the central issue that this thesis deals with. The basic thesis that initiated this study consideres that the ideas underlying the existing landscape planning (especially in Serbia) are not the ideas valid at the present time any more. Global processes have created a new environment for nowadays planning: planning for landscape is outdated. The current theoretical paradigm changes the focus or spatial concept. The landscape is no longer only a reserve of cultural and natural heritage that should be preserved in the same state, but it is a holistic, hybrid entity of natural, cultural and social values, which has been changing and evolving through time, and as such, becomes the subject of research. This paper provides elements for creating a different concept of planning through landscape, as an application model of the new paradigm that defines the spatial concept and planning principles. It integrates the application of scientific principles: landscape ecology, landscape aesthetics as a system and principles of communicative planning within the landscape as a spatial concept. In heuristic terms, descriptive and prescriptive theories of planning are unified, and solving scientific problems and tasks is based on: the concept of landscape as a whole, transdisciplinarity in research approach and landscape character as a new value in the planning system but also in an integral interpretation of knowledge about landscape. Spatial development issues in the interpretation of the new concept of planning, lead to the determination of type and character of the future landscape, which is public benefit and public interest, and where the objectives of all sectors are incorporated (housing, industry, agriculture, forestry, energy, environmental protection, natural and cultural heritage, ...). Level of integration and holism can prompt us towards the conclusion that offered or possible concept veries significantly from the existing one. And whether that concept is the basis for better planning and more beautiful landscapes, is the question of unpredictability of future development of planning in general. New questions and dilemmas have been raised, as it could have been predicted, given the experiences of the eternal search of an integrated planning model as well as the uncertainty of the planning itself... Univerzitet u Beogradu Šumarski fakultet Cvejić, Jasminka, 1947- Gazvoda, Davorin Medarević, Milan, 1951- Đorđević, Dejan, 1963- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=186 https://fedorabg.bg.ac.rs/fedora/get/o:5432/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/512668572 sr Autorstvo-Nekomercijalno 3.0 Srbija (CC BY-NC 3.0)

oai:eteze.bg.ac.rs:187 2013-08-01T00:00:00Z 1

Šumska zemljišta planine Javor u Republici Srpskoj Forest soils of Javor mountain in the Republic of Srpska Kapović, Marijana Javor planina, zemljišta, osobine, vegetacija, produktivnost Javor mountain, soils, characteristics, vegetation, productivity Datum odbrane: 05.03.2013. U disertaciji su prikazana šumska zemljišta Javor planine u Republici Srpskoj, a na bazi terenskih i laboratorijskih istraživanja osnovnih fizičkih i hemijskih osobina. Planina Javor se nalazi u istočnom dijelu Republike Srpske izmeñu opština Vlasenica, Han Pijesak i Kladanj (Federacija BiH). Pravac pružanja masiva Javor jeste sjeverozapad – jugoistok, a najveći vrh je Veliki Žep 1537 mn.v. Geološki je heterogeno, centralnim dijelom dominiraju krečnjaci, južne i jugozapadne padine pokrivaju pješčari, rožnjaci i glinci, sjeverne i sjeveroistočne krečnjaci – rožnjaci. Lokalno ima laporaca, jezerskih sedimenata i peridotita. Područje ima obilježja planinske klime sa kontinentalnim uticajem. Vrijednost srednje godišnje temperature na donjoj granici rasprostranjenja iznosi 6,2°C, a na gornjoj granici visinskog pojasa 3,8°C. U vegetacionom periodu padne prosječno 583 mm odnosno 57,7%. Prema veličini godišnjeg klimatskog indeksa dominira jako humidna klima, sa povećanjem visine postaje perhumidna. Najveći dio masiva Javor pokrivaju šume bukve i jele sa smrčom (Piceo – Abieti – Fagetum, Stef., et al. 1983). Izdvojeni su sledeći tipovi zemljišta: crnica, ranker, eutrično smeñe zemljište, kiselo smeñe zemljište, smeñe zemljište na krečnjaku, podzol, brunipodzol i ilimerizovano zemljište. Najrasprostranjeniji tipovi zemljišta na krečnjacima crnica i smeñe zemljište. Crnice su dobro razvijene, varijabilne dubine, struktuirane i humozne. Na grebenima, strmim padinama veoma su ugrožene od erozije. Smeñe krečnjačko zemljište je srednje duboko, najčešće dobro obezbijeñeno humusom, a produktivnost mu je odreñena dubinom, stepenom stjenovitosti i kamenitosti. Kiselo smeñe zemljište je dominantan tip zemljišta na silikatima Javora. Ovo je uglavnom srednje duboko do duboko zemljište. Humus je tipa moder. Ilovasta tekstura uz stabilnu sferoidnu strukturu obezbijeñuju povoljan vodno – vazdušni režim. Eutrični kambisol je lokalno rasprostranjen, srednje dubok, humozan. Tekstura mu varira u zavisnosti od supstrata. Podzoli se javljaju lokalno u Partizan polju. Ovo je duboko, pjeskovito i veoma siromašno zemljište. Brunipodzoli se razvijaju u uslovima manje kiselosti supstrata i manje su siromašni od podzola. Ilimerizovano zemljište je razvijeno na krečnjačkoj i silikatnoj podlozi... This dissertation presents forest soils of Javor Mountain in the Republic of Srpska, based on field and laboratory research of basic physical and hemical characteristics. Javor mountain is located in east part of the Republic of Srpske, between municipalities Vlasenica, Han Pijesak and Kladanj (Federation of Bosnia and Herzegovina). Geographical direction of massif is northwest - southeast, and the highest peak is 1537 meters above sea namely Veliki Žep. Geologicaly is heterogeneous, the central part is covered by limestones, southern and southwestern slopes covers sandstones, cherts and claystones, north and northeast slopes are covered with limestones and cherts. Localy we found marl, lake sediments and peridotite. The area has mountain climate with continental influences. Average value of annual temperature at the lowest level of mountain is 6.2°C, and the highest point has 3.8°C. In vegetation period average precipitation is 583 mm or 57.7%. According to the size of the annual climate index, very humid climate dominated and with higher altutide becomes perhumid. The biggest surface of Javor Mountain is covered by beech fir and spruce forests (Piceo - Abieti - Fagetum, Stef., et al. 1983). The following types of soil are separated: ranker, black soil, eutric brown soil, dystric brown soil, brown soil, podzol, brown podzolized soil and illimerized soil. The most prevalent soil type on limestones are black soil and brown soil. Black soils are well developed, with variable depth, well structured, humic, with a high adsorptive complex. On the ridges, steep slopes black soils are highly endangered by erosion. Brown soil on limestone is moderately deep, mostly with moderate humus level, and productivity is determined by their depth and degree of rockiness and stouniness. Acid brown soil is the dominant soil type on silicates of Javor Mountain. These are mainly moderately to very deep soils. Humus is moder type. Loam texture with a stable spheroidal structure provides advantageous water - air regime. Eutric brown soil is developed on small parts of mountain. Texture depends of character of substrate. Podzols are connected with specific acidophilic conditions in small parts of Partizan field. Brown podzolic soils are developed in condition of lower substrate acidity and they are not as poor as podzols are.... Univerzitet u Beogradu Šumarski fakultet Knežević, Milan N., 1953- Knežević, Milan N., 1953- Cvjetićanin, Rade, 1958- Marković, Mihajlo 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=187 https://fedorabg.bg.ac.rs/fedora/get/o:5434/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/512619676 sr Autorstvo-Nekomercijalno 3.0 Srbija (CC BY-NC 3.0)

oai:eteze.bg.ac.rs:189 2013-09-30T00:00:00Z 1

Uticaj akustičkog i biološkog šuma na kvalitet merenja signala otoakustičke emisije The influence of acoustic and biological noise on signal quality measurements of otoacoustic emissions Subotić, Miško Biološka osnova nastanka signala otoakusticke emisije (OAE), akusticka priroda njegovog nastanka i izuzetna maskiranost raznim oblicima smetnji jesu polazna osnova razvoja raznih metoda detekcije, obrade i interpretacije signala OAE, odnosno samog efekta otoakusticke emisije u svetlu karakterizacije funkcionisanja kohlee. Metode merenja OAE se razlikuju po nacinu generisanja stimulusa, mehanizmima generisanja odziva kao i po nacinima obrade signala i statistickog tumacenja dobijenih rezultata. Postojece metode merenja i obrade signala OAE jesu osnova savremenih sistema za merenje OAE, koji su našli široku primenu u klinickoj praksi. Meutim, nisu iscrpljene sve mogucnosti, pre svega teorijske a zatim i metodološke prirode, prvenstveno u domenu ekstrakcije signala OAE iz šuma. Poboljšanjem uslova merenja smanjuje se uticaj spoljašnje buke (šumova) na mogucnost ekstrakcije signala otoakusticke emisije i biološki šum postaje dominantan izvor smetnji. Istraživanje karakteristika bioloških šumova je jedan od preduslova za uspešno rešavanje problema detekcije OAE u prisustvu biološkog šuma. Na pažljivo odabranom uzorku, u skladu sa potrebama istraživanja, analizirani su biološki šumovi snimljeni u ušnom kanalu. Pokazalo se da postoji znacajna korelacija bioloških šumova u levom i desnom uhu i da koeficijent korelacije raste sa porastom intenziteta bioloških šumova. Ovakvo ponašanje bioloških šumova predstavlja povoljnu okolnost sa stanovišta primene adaptivnih metoda filtriranja i adaptivnih metoda potiskivanja šuma. U disertaciji su analizirane karakteristike najznacajnijih bioloških smetnji koje su prisutne kod merenja signala OAE. Ova saznanja su omogucila izbor optimalane adaptivne metode za detekciju TEOAE u prisustvu biološkog šuma. Osnovna ideja za potiskivanje biološkog šuma sastojala se u korišcenju biološkog šuma iz drugog ušnog c kanala za adaptivno potiskivanje biološkog šuma u ušnom kanalu u kome se meri OAE signal. Pošto je signal OAE duboko uronjen u šum, neophodno je bilo kombinovati nekoliko postupaka u toku predobrade signala kako bi se postiglo dobro potiskivanje šuma. Primenjeni su postupci adaptivnog filtriranja, ponderisanog usrednjavanja i oduzimanja procenjene vrednosti signala OAE od signala odziva snimljenog u ušnom kanalu... OAE, TEOAE, biological noise, ambient noise, adaptive filter, adaptive suppression of noise, hearing loss, screening program Datum odbrane: 21.02.2013. Biološka osnova nastanka signala otoakusticke emisije (OAE), akusticka priroda njegovog nastanka i izuzetna maskiranost raznim oblicima smetnji jesu polazna osnova razvoja raznih metoda detekcije, obrade i interpretacije signala OAE, odnosno samog efekta otoakusticke emisije u svetlu karakterizacije funkcionisanja kohlee. Metode merenja OAE se razlikuju po nacinu generisanja stimulusa, mehanizmima generisanja odziva kao i po nacinima obrade signala i statistickog tumacenja dobijenih rezultata. Postojece metode merenja i obrade signala OAE jesu osnova savremenih sistema za merenje OAE, koji su našli široku primenu u klinickoj praksi. Meutim, nisu iscrpljene sve mogucnosti, pre svega teorijske a zatim i metodološke prirode, prvenstveno u domenu ekstrakcije signala OAE iz šuma. Poboljšanjem uslova merenja smanjuje se uticaj spoljašnje buke (šumova) na mogucnost ekstrakcije signala otoakusticke emisije i biološki šum postaje dominantan izvor smetnji. Istraživanje karakteristika bioloških šumova je jedan od preduslova za uspešno rešavanje problema detekcije OAE u prisustvu biološkog šuma. Na pažljivo odabranom uzorku, u skladu sa potrebama istraživanja, analizirani su biološki šumovi snimljeni u ušnom kanalu. Pokazalo se da postoji znacajna korelacija bioloških šumova u levom i desnom uhu i da koeficijent korelacije raste sa porastom intenziteta bioloških šumova. Ovakvo ponašanje bioloških šumova predstavlja povoljnu okolnost sa stanovišta primene adaptivnih metoda filtriranja i adaptivnih metoda potiskivanja šuma. U disertaciji su analizirane karakteristike najznacajnijih bioloških smetnji koje su prisutne kod merenja signala OAE. Ova saznanja su omogucila izbor optimalane adaptivne metode za detekciju TEOAE u prisustvu biološkog šuma. Osnovna ideja za potiskivanje biološkog šuma sastojala se u korišcenju biološkog šuma iz drugog ušnog c kanala za adaptivno potiskivanje biološkog šuma u ušnom kanalu u kome se meri OAE signal. Pošto je signal OAE duboko uronjen u šum, neophodno je bilo kombinovati nekoliko postupaka u toku predobrade signala kako bi se postiglo dobro potiskivanje šuma. Primenjeni su postupci adaptivnog filtriranja, ponderisanog usrednjavanja i oduzimanja procenjene vrednosti signala OAE od signala odziva snimljenog u ušnom kanalu... Biological basis of the otoacoustic emission signal (OAE), acoustic nature of its generation and exceptional masking with various forms of interference are the starting point for the development of various methods of detection, signal processing and interpretation of OAE signal, or the effect of otoacoustic emission in light of the characterization of the cochlea functioning. OAE measurement methods differ in the way of stimulus generation, response generation mechanisms and the methods of signal processing and statistical interpretation of results. Existing methods of measurement and OAE signal processing are the basis of modern systems for OAE measurement, which have found wide application in clinical practice. However, all possibilities are not exhausted, especially the theoretical and methodological nature aproaches, primarily in the field of OAE signal extraction from the noise. Improvement of the measuring conditions reduces the influence of external noise on the possibility of extraction of otoacoustic emissions, and biological noise becomes the dominant source of interference. The study of characteristics of biological noise is one of the prerequisites for successful troubleshooting OAE detection in the presence of biological noise. In carefully selected sample, in accordance with the needs of research, we analyzed the biological noise recorded in the ear canal. It turned out that there was a significant correlation of biological noise in the left and right ear and the correlation coefficient increases with the intensity of biological noise. This behavior of biological noise is a favorable circumstance from the point of application of adaptive filtering methods and adaptive noise suppression method. The dissertation analyzes the characteristics of the most important form of biological interference that are present during OAE measurement. These findings have enabled the selection of optimal adaptive methods for the detection of TEOAE in the presence of biological noise. The basic idea of suppressing biological noise consisted in e the use of biological noise from the other ear canal for adaptive suppression of biological noise in the ear canal in which OAE signal is measured. Since the OAE signal is deeply immersed in the noise it was necessary to combine several steps during preprocessing the signal to achieve good noise suppression. The applied methods are adaptive filtering, weighted averaging and estimated value of OAE signal subtraction from the signal response recorded in the ear canal... Univerzitet u Beogradu Elektrotehnički fakultet Jovičić, Slobodan Mijić, Miomir, 1951- Pavlović-Šumarac, Dragana Šarić, Zoran Radunović, Jovan 2013 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=189 https://fedorabg.bg.ac.rs/fedora/get/o:5430/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/43470351 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:190 2013-08-03T00:00:00Z 1

Таксономска и еколошка истраживања врста рода Vaccinium L. у Србији Taxonomic and ecological investigation of Vaccinium L. genus in Serbia Bjedov, Ivana R., 1975- Vaccinium myrtillus, V. uliginosum,V. vitis-idaea, морфо- анатомске карактеристике листова, RAPD маркери, генетички диверзитет и варијабилност, фитоценозе, тешки метали, VSD модел, одрживост Vaccinium myrtillus, V. uliginosum, V. vitis-idaea, morphoanatomical characteristics of leaves, RAPD markers, genetic diversity and variability, phytocenosis, heavy metals, VSD model, sustainability Datum odbrane: 20.11.2012. Врсте рода Vaccinium су листопадни или зимзелени жбунови или полужбунови које се сврставају у фамилију Ericaceae. Широко су распрострањене у планинским регионима централне Европе, као и у бореалним и суб-арктичким регионима северне Европе, посебно у приземном спрату четинарских шума. На подручје Србије у брдским и планинским регионима налазе се три врсте овог рода: V. myrtillus, V. uliginosum и V. vitis-idaea. Ове врсте су дугоживеће, њихова репродуктивна стратегија обухвата и вегетативно и генеративно размножавање, њихове цветове опрашују инсекти или су самооплодне, а семена разносе птице. Резултати добијени морфо-анатомским истраживањима одабраних карактера листова проучаваних врста статистички су обрађени коришћењем програма “Statistica” (StatSoft, Inc., Tulsa, OK, USA). На основу анализираник морфо-анатомских карактера листова, утврђена је јасна диференцијација између проучаваних врста, док се диференцијација између популација у оквиру исте врсте не уочава. Варијабилност проучаваних морфо – анатомских карактеристика листова доведена је у везу са одређеним еколошким факторима. Кластер анализом морфо- анатомских карактеристика листова указала је на могућност постојање генетичке варијабилности између популација, што је потврђено молекуларно – генетичким истраживањима. За потребе молекуларно-генетичких истраживања, ДНК је изолована из младих листова проучаваних врста. За проучавање генетичког диверзитета и варијабилности коришћени су RAPD маркери. Обрада података вршена је употребом неколико софтвера: POPGENE, PAST, NTSYSpc, Arlequin и STRUCTURE 2.2... The species of the Vaccinium genus include deciduous or evergreen shrubs which belong to the family Ericaceae. They are widespread in the mountainous regions of central Europe and in the boreal and sub-arctic regions of northern Europe, particularly on the ground floor of coniferous forests. In the hilly and mountainous regions on the territory of Serbia, three species of this genus are described: V. myrtillus, V. uliginosum and V. vitis-idaea. These species are longlived, their reproductive strategy includes vegetative and generative reproduction, their flowers are pollinated by insects, they can also be selfpollinated, and their seeds are dispersed by birds. The results obtained by morpho-anatomical investigation of leaves were statistically analyzed using the program “Statistica” (StatSoft, Inc., Tulsa, OK, USA). Based on the analysis of the morpho-anatomical character of leaves, a clear differentiation between the investigated species was noticed, while the differentiation between the populations within the same species was not observed. The variability of the studied morpho - anatomical leaf characteristics were correlated with certain environmental factors. The cluster analysis of morpho-anatomical leaf characteristics indicated the possibility of the existence of genetic variation among the populations, which was confirmed by molecular - genetic research. For the purposes of molecular genetic studies, DNA was extracted from young leaves of the studied species. For the study of genetic diversity and variability RAPD markers were used. Data analysis was performed using several kinds of software: POPGENE, PAST, NTSYSpc, Arlequin and STRUCTURE 2.2... Univerzitet u Beogradu Šumarski fakultet Obratov-Petković, Dragica, 1956- Marin, Petar, 1957- Dajić-Stevanović, Zora, 1962- Aleksić, Jelena, 1970- Đukić, Matilda, 1952- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=190 https://fedorabg.bg.ac.rs/fedora/get/o:5435/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/512521628 sr Autorstvo-Nekomercijalno 3.0 Srbija (CC BY-NC 3.0)

oai:eteze.bg.ac.rs:191 2013-09-24T00:00:00Z 1

Еколошки и економски ефекти одрживог управљања земљишним ресурсима планинског подручја општине Љубовија Ecological and economic effects in sustainable land management in the mountainous region of the municipality of Ljubovija Todosijević, Mirjana M., 1971- губици земљишта, ерозија, конзервационе мере, одрживо управљање soil loss, erosion, conservation measures, economic effects, sustainable management Datum odbrane: 02.07.2012. Савремени свет је суочен са потребом заједничке одговорности за развој у складу са потребама људи и природе и схватањем да се планета Земља мора очувати како за садашњу, тако и за будуће генерације људи на прихватљив начин. Одрживо управљање земљишним ресурсима се заснива на очувању земљишног ресурса и планирању производње која ће имати позитивне ефекте. Планински регион је подручје где су процеси деградације земљишта изражени а производне могућности ограничене, што доводи у питање елементарне услове за живот и рад људи. Да бе се ти ефекти ублажили, предложен је концептуални модел одрживог управљања земљишним ресурсима планинског подручја. Представља јединство еколошких и економских параметара у просторном, временском и управљачком смислу. У сливу Трешњице, губици земљишта изазвани дејством ерозионих процеса су велики, а продуктивност мала. Степен угрожености земљишта процесима ерозије, оцењен је методом потенцијала ерозије (метод проф. Гавриловића), и USLE моделом (Универзална једначина губитака земљишта). Уз примену WOCAT методологије, за одређене геофизичке, социо-економске и институционалне услове, предложени су рехабилитациони приступи и технике одрживог управљање земљишним ресурсима... shared responsibility for a development that is in line with the needs of people and nature, and consideration of the fact that the Earth must be preserved both for the present and future generations of people in an acceptable way. Sustainable management of land resources is based on the conservation of soil resources by planning a production with positive effects. Mountainous regions are areas with significant processes of soil degradation and a limited production capacity, which predetermines the basic living and working conditions of the local people. A conceptual model for a sustainable management of land resources in mountainous areas has been proposed with the aim of mitigating these effects. This model represents the unity of ecological and economic parameters in terms of space, time and management. In the basin of the Trešnjica River, the soil losses caused by the influence of soil erosion processes is high and the productivity is low. The degree of soil vulnerability to erosion processes was evaluated using the erosion potential method (established by Prof. Gavrilovic), and the USLE model (Universal Soil Loss |Equation). Along with the implementation of the WOCAT methodology for specific geophysical, socio-economic and institutional conditions, rehabilitation approaches and techniques for sustainable management of soil resources have been proposed... Univerzitet u Beogradu Šumarski fakultet Zlatić, Miodrag, 1953- Dragović, Nada, 1959- ( Kadović, Ratko, 1945- Kostadinov, Stanimir, 1946- Vukelić, Gordana, 1958- 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=191 https://fedorabg.bg.ac.rs/fedora/get/o:5437/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/512422300 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:192 2013-11-15T00:00:00Z 1

Komparativna analiza agenasa za biološku kontrolu patogenih gljiva izolovanih sa lekovitih biljaka Comparative analysis of agents for biological of pathogenic fungi isolated from medicinal plants Stević, Tatjana, 1970- Fitopatogene gljive, biološka kontrola, etarska ulja, antifungalna aktivnost, izolati Bacillus sp., ekstrakti izolata antagonista, antagonizam Pathogenic fungi, biological control, essential oils, antifungal activity, Bacillus sp. isolates, lipopeptide extracts of isolates, antagonism Datum odbrane: 23.04.2013. Primena lekovitog bilja i njihovih preparata u prevenciji i lečenju različitih poremećaja u ljudskom organizmu može biti ograničena njihovom mogućom kontaminacijom fitopatogenim gljivama i mikotoksinima. Saznanja o riziku pri primeni hemijskih fungicida po rukovaoca, potrošača i životnu sredinu, dovela su do povećanja interesa za uvođenje alternativnih mera u zaštiti bilja, gde posebno mesto pripada preparatima prirodnog porekla tzv. agensima biološke kontrole. Biološka kontrola podrazumeva primenu korisnih mikroorganizama (bakterija, kvasaca, gljiva) ili produkata njihovog metabolizma, kao i primenu biljnih ekstrakata i etarskih ulja u zaštiti biljaka. Ispitivanjem preko 40 vrsta lekovitog bilja najlošiji mikrobiološki kvalitet utvrđen je za sledeće droge: kukuruznu svilu, list i herbu nane, list koprive, herbu rastavića i cvet nane. Iako su na svim biljnim drogama utvrđene mešovite infekcije gljivama iz različitih rodova, većina izolovanih vrsta gljiva pripada rodu Fusarium, a potom Aspergillus i Alternaria. Osim pomenutih, identifikovani su i predstavnici rodova: Penicillium, Phoma, Cephalosporium, Nigrospora, Cladosporium, Epicoccum, Gliocladium, Myrothecium, Cercospora, Phomopsis, Verticillum, Dreschlera (=Bipolaris), Rhizoctonia, Septoria, Trichoderma, Curvularia, Stahybotrys, Trichotecium, Puccinia, Botrytis, Mucor i Rhizopus sp., u zavisnosti od biljne droge. U cilju pronalaženja efikasnog biokontrolog agensa ispitivali smo mogućnost primene etarskih ulja i izolata Bacillus sp. u kontroli odabranih identifikovanih gljiva. U tom smislu, odabrali smo sledeće vrste gljiva: Fusarium solani, F. equiseti, F. oxysporum (izolovani sa kukuruzne svile i nevena), F. tricinctum, F. semitectum, F. sporotrichioides, F. subglutinans, Aspergillus flavus, A. niger, Alternaria alternata, Penicillium sp., Chaetomium sp., Curvularia lunata, Trichoderma viride, Trichotecium roseum, Gliocladium roseum, Myrotechium verrucaria, Phoma sp., Phomopsis sp. i Verticillium dahliae... The application of medicinal plants and their preparations for the prevention and treatment of various disorders in humans may be limited by the possible contamination with phytopathogenic fungi and mycotoxins. Risk of using chemical fungicides for the operator, the consumer and the environment, have led to increasing interest in the introduction of alternative measures in plant protection. Lately, preparations of natural origin, so-called biological control agents are in the focus of investigation. Biological control involves the use of beneficial microorganisms (bacteria, yeasts, fungi) or the products of their metabolism, as well as the application of plant extracts and essential oils in plant protection. Examining over 40 stored dried medicinal plant species the lowest microbial quality were determined for next herbal drugs: Maydis stigmata (corn silk), Mentha leaf and herb (mint herb and leaf), Urtica leaf (nettle leaf), Equisetum herb (horsetail herb) and Calendula flower (marigold flower). Although mixed infections was recorded with different types of fungus the Fusarium was noted as the most dominant genera for most tested drugs, followed by Aspergillus and Alternaria. Twelve species of the genus Fusarium was identified. In addition, species from the following genera were identified: Phoma, Cephalosporium, Nigrospora, Cladosporium, Epicoccum, Gliocladium, Myrothecium, Cercospora, Phomopsis, Verticillum, Dreschlera (=Bipolaris), Rhizoctonia, Septoria, Trichoderma, Curvularia, Stahybotrys, Trichotecium, Puccinia, Botrytis, Mucor and Rhizopus sp. depending on plant species. In order to find an effective biological control agent, we investigated the possibility of applying the essential oils and isolates of Bacillus sp. in the control of selected identified fungi. In this regard, we chose the following fungal species: Fusarium solani, F. equiseti, F. oxysporum (isolated from corn silk and marigold flower), F. tricinctum, F. semitectum, F. sporotrichioides, F. subglutinans, Aspergillus flavus, A. niger, Alternaria alternata, Penicillium sp., Chaetomium sp., Curvularia lunata, Trichoderma viride, Trichotecium roseum, Gliocladium roseum, Myrotechium verrucaria, Phoma sp., Phomopsis sp. and Verticillium dahliae... Univerzitet u Beogradu Biološki fakultet Berić, Tanja, 1974- Šavikin, Katarina Stanković, Slaviša, 1965- Soković, Marina Gođevac, Dejan 2013 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=192 https://fedorabg.bg.ac.rs/fedora/get/o:5438/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/43480335 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)

oai:eteze.bg.ac.rs:193 2013-11-15T00:00:00Z 1

Antitumorski efekat steroidnih tetraoksana na maligno transformisane ćelijske linije čoveka Antitumor effect of steroidal tetraoxanes on malignantly transformed human cell lines Žižak, Željko S., 1965- Antitumorski lekovi, apoptoza, artemizinin, citotoksičnost, ćelijski ciklus, hemioterapija, peroksidi, reaktivne vrste kiseonika, tetraoksani Anticancer drugs, apoptosis, artemisinin, cytotoxicity, cell cycle, chemotherapy, peroxides, reactive oxygen species, tetraoxanes Datum odbrane: 27.12.2012. Uvod: Pronalaženje agenasa sa potencijalnim antitumorskim dejstvom je imperativ u modernoj onkologiji. Pri tome se sve više zapaža da određene hemijske strukture imaju specifičnije toksično dejstvo na maligne ćelije. Otkriće artemizinina je označilo početak istraživanja peroksida kao potencijalne zamene za tradicionalne antimalarijske lekove, a iz ovih istraživanja nastala je i strukturno jednostavna klasa peroksida - 1,2,4,5-tetraoksani, za koje je ubrzo pokazano da pored antimalarijskog pokazuju i snažan antiproliferativni efekat. Maligne ćelije imaju poremećaje u regulatornim mehanizmima koji upravljaju ćelijskom proliferacijom i homeostazom. Sposobnost tumorskih ćelijskih populacija da povećaju broj ćelija je određena ne samo intenzitetom ćelijske proliferacije, već i brzinom uklanjanja ćelija. Programirana ćelijska smrt - apoptoza, predstavlja glavni izvor ovog uklanjanja. Cilj rada je bio da se odredi nivo citotoksičnog dejstva grupe mešovitih tetraoksana prema različitim humanim malignim ćelijama, kao i da se odredi koeficijenat selektivnosti u njihovom dejstvu u odnosu na zdrave imunokompetentne ćelije. U cilju dobijanja uvida u mehanizam dejstva ispitivanih jedinjenja odrediće se tip ćelijske smrti koju indukuju ispitivani tetraoksani, kao i produkcija reaktivnih kiseoničnih vrsta u Hela ćelijama. Cilj 3D QSAR studije o antiproliferativoj aktivnosti trideset tri 1,2,4,5-tetraoksanska derivata prema Hela i Fem-x tumorskim ćelijskim linijama, je bio da se utvrdi koje su najvažnije farmakofore steroidnih tetraoksana koje utiču na potenciju ispitivanih jedinjenja prema HeLa i Fem-x tumorskim ćelijskim linijama. Materijal i metode: Citotoksično dejstvo tetraoksana DO-122 - DO-124 i DO-126 - DO-128, prema pet tumorskih ćelijskih linija je ispitivano standardnim MTT testom. U cilju određivanja tipa ćelijske smrti indukovane tretmanom ispitivanim tetraoksanima načinjena je morfološka analiza HeLa ćelija obojenih smešom akridin oranža i etidijum bromida. Analiza određivanja distribucije faza ćelijskog ciklusa HeLa ćelija obojenih propidijum jodidom, urađena je na protočnom citometru. Produkcija intraćelijskih reaktivnih vrsta kiseonika (ROS) je merena fluorometrijski pomoću fluorescentne boje 2’,7’-dihlorodihidrofluorescein diacetata. Zavisnost strukture i funkcije trideset tri 1,2,4,5-tetraoksanskih derivata prema HeLa i Fem-x ćelijskim linijama pokazana je 3D QSAR studijom... Univerzitet u Beogradu Biološki fakultet Radenović, Lidija. 1966- Juranić, Zorica. Šolaja, Bogdan, 1951- Opsenica, Dejan 2012 PhD thesis application/pdf https://eteze.bg.ac.rs/application/showtheses?thesesId=193 https://fedorabg.bg.ac.rs/fedora/get/o:5439/bdef:Content/download https://plus.cobiss.net/cobiss/sr/sr/bib/1024559794 sr Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0) 1775659340450