Uspostavljanje programa selektivnog uzgoja kalifornijske pastrmke (oncorhynchus mykiss, walbaum) u Srbiji

Zahtev za sve većim količinama hrane za ljudsku upotrebu, efikasnost iskorišćavanja hraniva i prostora za gajenje domaćih životinja, kao i pojava mnogih bolesti doveli su do intenzivnog razvijanja selekcionih programa u svim granama poljoprivrede. Za razliku od ostalih gajenih životinja, programi selekcije u akvakulturi su se razvili nešto kasnije usled nedostatka potrebnih procena heritabilnosti, koeficijenata varijacija i korelacija za ekonomski bitne osobine. Trenutno se u akvakulturi samo 1-2% od ukupne proizvodnje zasniva na genetički unapređenim vrstama riba (Gjedrem, 1997). Korišćenjem selektovanih linija riba postiže se više korisnih stvari. Na prvom mestu, programi selekcije riba predstavljaju jedini način stalnog unapređenja ekonomski bitnih osobina kao sto su prirast, konverzija hrane, otpornost na bolesti, smanjenje masnoće u mesu riba. Ribe iz selektovanih linija efikasnije iskorišćavaju hraniva i na taj način smanjuju pritisak na divlje populacije riba koje se koriste za proizvodnju ribljeg brašna, kao glavnog izvora proteina u smešama za ishranu pastrmki. Ribe koje potiču iz divljine ne napreduju zadovoljavajućim brzinom, što znači da su konstantno pod stresom, za razliku od riba poreklom iz selekcionih programa koje pokazuju manji uticaj stresa usled gajenja u zarobljeništvu. Tako se na ovaj način korišćenjem selektovanih linija riba postiže efikasna i održiva proizvodnja uz vođenje računa o dobrobiti životinja. Drugi dobar razlog za uspostavljanje programa selekcije pastrmke u Srbiji je dobro dokumentovano postojanje interakcije genotip x okolina kod kalifornijske pastrmke, kao što su pokazala istraživanja (McKay et al., 1984; Hanke et al., 1989; Sylven et al., 1991; Winkelman and Peterson, 1994; Kettunen et al., 1999; Kause et al., 2003). Na kraju, ali ne i najmanje važna je i kontrola bolesti kod kalifornijske pastrmke i mogućnost stvaranja otpornih linija pastrmki na neke bolesti putem selektivnog uzgoja (Henrion, 2005). Jedno od rešenja za ovaj ozbiljan problem, pored boljeg sistema kontrole pastrmske ikre poreklom iz uvoza, je i stvaranje lokalnih selektovanih matičnih jata sa proverenim poreklom i povećenom otpornošću na bolesti. Obzirom da za kalifornijsku pastrmku postoje pouzdani podaci o varijabilnosti i heritabilnosti proizvodnih osobina ovo pruža mogućnost efikasne selekcije, a samom tim i značajnog unapređenja proizvodnje uz smanjen ukupni mortalitet, putem odgovarajućeg programa selekcije u Srbiji

Center for Fishery and Applied Hydrobiology “Little Danube”, Experimental School Estate “Radmilovac”: Synergy of Research, Economy and Society

In every society, initiators and promoters of the development are individuals, teams or institutions with a vision, good ideas, seriousness, but above enthusiasm to work hard. They trace the road and drive activities related to research and/or economy. In the Serbian aquaculture sector such institutions is the Faculty of Agriculture and its Center for Fishery and Applied Hydrobiology (CEFAH) (or the “Little Danube”), which operates within the Experimental school estate “Radmilovac”. The Center started to be established in 2007. Unlike other similar Centers built by state resources intended for research and scientific work, the “Little Danube” was created much more as a result of enthusiasm of a group of researchers and their readiness to cooperate with national and international institutions, but also by enthusiasm of individuals ready to financially or materially help some of the Center’s programs. The Center’s activities are directed towards improving and developing the research and economy in aquaculture. Today the Center in “Radmilovac” and its laboratories located in the building of the Faculty of Agriculture represent an education and research polygon for aquaculture development. The education part is aimed at all levels: from pre-school and elementary school level by educational visits to the “Little Danube”, where they get to know different fish species and other aquatic organisms, their culture, fishing, fishing tools; to PhD level students and researchers that increase their knowledge and skills in the Center. CEFAH is a scientific polygon: in its aquaria, tanks, RAS systems, as well as in a number of earthen ponds a range of various experiments in different areas of aquaculture are carried out and knowledge is transferred directly in aquaculture economy. The development of Serbian aquaculture is directly affected by the connection of the Center with the economy through realization of biotechnology projects, fish selective breeding programs, and experiments

Modelling cholesterol effects on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis

A mathematical model of the hypothalamic-pituitary-adrenal (HPA) axis with cholesterol as a dynamical variable was derived to investigate the effects of cholesterol, the primary precursor of all steroid hormones, on the ultradian and circadian HPA axis activity. To develop the model, the parameter space was systematically examined by stoichiometric network analysis to identify conditions for ultradian oscillations, determine conditions under which dynamic transitions, i.e. bifurcations occur and identify bifurcation types. The bifurcations were further characterized using numerical simulations. Model predictions agree well with empirical findings reported in the literature, indicating that cholesterol levels may critically affect the global dynamics of the HPA axis. The proposed model provides a base for better understanding of experimental observations, it may be used as a tool for designing experiments and offers useful insights into the characteristics of basic dynamic regulatory mechanisms that, when impaired, may lead to the development of some modern-lifestyle-associated diseases

Dynamic transitions in a model of the hypothalamic-pituitary-adrenal axis

Dynamic properties of a nonlinear five-dimensional stoichiometric model of the hypothalamicpituitary-adrenal (HPA) axis were systematically investigated. Conditions under which qualitative transitions between dynamic states occur are determined by independently varying the rate constants of all reactions that constitute the model. Bifurcation types were further characterized using continuation algorithms and scale factor methods. Regions of bistability and transitions through supercritical Andronov-Hopf and saddle loop bifurcations were identified. Dynamic state analysis predicts that the HPA axis operates under basal (healthy) physiological conditions close to an Andronov-Hopf bifurcation. Dynamic properties of the stress-control axis have not been characterized experimentally, but modelling suggests that the proximity to a supercritical Andronov-Hopf bifurcation can give the HPA axis both, flexibility to respond to external stimuli and adjust to new conditions and stability, i.e., the capacity to return to the original dynamic state afterwards, which is essential for maintaining homeostasis. The analysis presented here reflects the properties of a low-dimensional model that succinctly describes neurochemical transformations underlying the HPA axis. However, the model accounts correctly for a number of experimentally observed properties of the stress-response axis. We therefore regard that the presented analysis is meaningful, showing how in silico investigations can be used to guide the experimentalists in understanding how the HPA axis activity changes under chronic disease and/or specific pharmacological manipulations

Stanje ribarstva u Srbiji

Fishery in Serbia comprises of aquaculture and fishery. Aquaculture in Serbia concerns fish culturing. For production of other aquatic animals, mainly ornamental plants and crayfish, only occasional interest and small scale production in aquarium type of units exists. Fish are produced in carp and trout fish farms (over 95%), to a smaller extent in cages, enclosed or partitioned natural or man made aquatic ecosystems. Aquaria fish culture is mainly low scale, with a small number of specialized breeders and one public aquarium (M a r k o v i ć i M i t r o v i ć T u t u n d ž i ć, 2003, 2005; M a r k o v i ć i P o l e k s i ć, 2007, M a r k o v i ć i sar., 2009). In Serbia freshwater species cultured are: common carp, white and gray bighead, wells, pike perch, rainbow trout and to a lesser degree Northern pike, tench, brown trout, beluga, Russian starlet. There is 13 500 – 14 000 ha of fish farms in Serbia, with 99.9% of carp farms and 0.1% of trout farms. The total fish production in recent years is between 10 000 and 15 000 tons with 70 to 75% of consumable fish. All three types of production systems are present: extensive, semi-intensive and intensive. Extensive production is sporadic and is present only at a few carp production units, mostly not economic for semi-intensive production due to remoteness from other production units or neglect. The principal type of production (75 – 80%) is semi-intensive production of cyprinids, with common carp as the main species. Common carp is present with more than 80% of the total production in warmwater fish farms. The traditional (old) type of feeding is slowly changing. Cereals are more often, at over 50% of production surfaces, totally of partially replaced by complete, peletted and even more extruded feed. This has resulted in an increase of production per surface unit in recent years. Intensive production systems in carp culture are less present, at a small number of earthen ponds with aeration systems, mainly for fish fry production, and in cages. However, rainbow trout, the only salmonid species cultured for consummation, is exclusively produced in intensive systems at trout farms in Serbia. The number of people involved full-time in fish production in Serbia is about 1100 and approximately 400 seasonal workers that are hired mainly prior to harvest. With the rising of standard and returning to traditional habits during religious fasting, as well as with a slow increase of “healthy food” supporters, fish consumption has a growing trend. However, although fish production is increasing in recent years, the country’s production and open-water capture fishery barely represent a quarter of the total needs of inhabitants. This results in increase of import, mainly marine and frizzed fish, but also freshwater fish. Open-water capture fishery is performed in Serbia’s fishing waters. They are represented by 66 000 km of water currents (rivers and streams), flood plains, backwaters, 50 lakes, 150 reservoir lakes and around 30 000 km of canal systems, hydromeliorative systems, as well as all other waters with fish. All fishing waters are divided into 6 fishing regions (Serbia – Vojvodina, Serbia – West, Serbia – South West, Srbia - South, Serbia – East, Serbia – Center) since year 2007. Sports fishing is obtainable at all regions but commercial fishery is aloud only at two regions (Serbia – Vojvodina, Serbia – west), and in rivers Tisa, Sava and Danube. Number of fisherman with purchased license in the last couple of years is between 50 000 and 100 000. Number of commercial fishermen is between 500 and 2000 in the last ten years. The amount of captured fish is between 2000 and 3000 tons in the few past years

Does Prenatal Stress Shape Postnatal Resilience? – An Epigenome-Wide Study on Violence and Mental Health in Humans

Stress during pregnancy widely associates with epigenetic changes and psychiatric problems during childhood. Animal studies, however, show that under specific postnatal conditions prenatal stress may have other, less detrimental consequences for the offspring. Here, we studied mental health and epigenome-wide DNA methylation in saliva following intimate partner violence (IPV) during pregnancy in São Gonçalo, a Brazilian city with high levels of violence. Not surprisingly, mothers exposed to pregnancy IPV expressed elevated depression, PTSD and anxiety symptoms. Children had similar psychiatric problems when they experienced maternal IPV after being born. More surprisingly, when maternal IPV occurred both during (prenatal) and after pregnancy these problems were absent. Following prenatal IPV, genomic sites in genes encoding the glucocorticoid receptor (NR3C1) and its repressor FKBP51 (FKBP5) were among the most differentially methylated and indicated an enhanced ability to terminate hormonal stress responses in prenatally stressed children. These children also showed more DNA methylation in heterochromatin-like regions, which previously has been associated with stress/disease resilience. A similar relationship was seen in prenatally stressed middle-eastern refugees of the same age as the São Gonçalo children but exposed to postnatal war-related violence. While our study is limited in location and sample size, it provides novel insights on how prenatal stress may epigenetically shape resilience in humans, possibly through interactions with the postnatal environment. This translates animal findings and emphasizes the importance to account for population differences when studying how early life gene–environment interactions affects mental health

Phenotypic Modulation of Smooth Muscle Cells in Atherosclerosis Is Associated With Downregulation of LMOD1, SYNPO2, PDLIM7, PLN, and SYNM

OBJECTIVE: Key augmented processes in atherosclerosis have been identified, whereas less is known about downregulated pathways. Here, we applied a systems biology approach to examine suppressed molecular signatures, with the hypothesis that they may provide insight into mechanisms contributing to plaque stability. APPROACH AND RESULTS: Muscle contraction, muscle development, and actin cytoskeleton were the most downregulated pathways (false discovery rate=6.99e-21, 1.66e-6, 2.54e-10, respectively) in microarrays from human carotid plaques (n=177) versus healthy arteries (n=15). In addition to typical smooth muscle cell (SMC) markers, these pathways also encompassed cytoskeleton-related genes previously not associated with atherosclerosis. SYNPO2, SYNM, LMOD1, PDLIM7, and PLN expression positively correlated to typical SMC markers in plaques (Pearson r>0.6, P0.8, P<0.0001). By immunohistochemistry, the proteins were expressed in SMCs in normal vessels, but largely absent in human plaques and intimal hyperplasia. Subcellularly, most proteins localized to the cytoskeleton in cultured SMCs and were regulated by active enhancer histone modification H3K27ac by chromatin immunoprecipitation-sequencing. Functionally, the genes were downregulated by PDGFB (platelet-derived growth factor beta) and IFNg (interferron gamma), exposure to shear flow stress, and oxLDL (oxidized low-density lipoprotein) loading. Genetic variants in PDLIM7, PLN, and SYNPO2 loci associated with progression of carotid intima-media thickness in high-risk subjects without symptoms of cardiovascular disease (n=3378). By eQTL (expression quantitative trait locus), rs11746443 also associated with PDLIM7 expression in plaques. Mechanistically, silencing of PDLIM7 in vitro led to downregulation of SMC markers and disruption of the actin cytoskeleton, decreased cell spreading, and increased proliferation. CONCLUSIONS: We identified a panel of genes that reflect the altered phenotype of SMCs in vascular disease and could be early sensitive markers of SMC dedifferentiation

Mutations in DSTYK and dominant urinary tract malformations.

ABSTRACT Introduction Congenital abnormalities of the kidney of the urinary tract are the most common cause of pediatric kidney failure. These disorders are highly heterogeneous, and their etiology is poorly understood. Methods We performed genome-wide linkage analysis and whole-exome sequencing in a family with autosomal dominant congenital abnormalities of the kidney of the urinary tract (7 affected family members). We also performed sequence analysis in 311 unrelated patients, as well as histologic and functional studies. Results Linkage analysis identified five regions of the genome that were shared among all affected family members. Exome sequencing identified a single rare deleterious variant within these linkage intervals, a heterozygous splice-site mutation in dual serine/threonine and tyrosine protein kinase (DSTYK). This variant, which resulted in aberrant gene product splicing, was present in all affected family members. Additional independent DSTYK mutations, including nonsense and splice-site mutations, were detected among 7/311 unrelated patients. DSTYK is highly expressed in the maturing epithelia of all major organs, localizing to cell membranes. Knockdown in zebrafish resulted in multi-organ developmental defects, resembling loss of fibroblast growth factor (FGF) signaling. Consistent with this finding, DSTYK colocalizes with FGF receptors in the ureteric bud and metanephric mesenchyme. Finally, DSTYK knockdown in human embryonic kidney cells inhibited FGF-stimulated ERK-phosphorylation, the principal signal downstream of receptor tyrosine kinases. Conclusions We detected DSTYK mutations in 2.2% of patients with congenital abnormalities of the kidney and urinary tract whom we studied, suggesting that DSTYK is a major determinant of human urinary tract development, downstream of FGF signaling

Distinct roles of the RasGAP family proteins in C. elegans associative learning and memory

The Ras GTPase activating proteins (RasGAPs) are regulators of the conserved Ras/MAPK pathway. Various roles of some of the RasGAPs in learning and memory have been reported in different model systems, yet, there is no comprehensive study to characterize all gap genes in any organism. Here, using reverse genetics and neurobehavioural tests, we studied the role of all known genes of the rasgap family in C. elegans in associative learning and memory. We demonstrated that their proteins are implicated in different parts of the learning and memory processes. We show that gap-1 contribute redundantly with gap-3 to the chemosensation of volatile compounds, gap-1 plays a major role in associative learning, while gap-2 and gap-3 are predominantly required for short- and long-term associative memory. Our results also suggest that the C. elegans Ras orthologue let-60 is involved in multiple processes during learning and memory. Thus, we show that the different classes of RasGAP proteins are all involved in cognitive function and their complex interplay ensures the proper formation and storage of novel information in C. elegans

Microarray-Based Maps of Copy-Number Variant Regions in European and Sub-Saharan Populations

The genetic basis of phenotypic variation can be partially explained by the presence of copy-number variations (CNVs). Currently available methods for CNV assessment include high-density single-nucleotide polymorphism (SNP) microarrays that have become an indispensable tool in genome-wide association studies (GWAS). However, insufficient concordance rates between different CNV assessment methods call for cautious interpretation of results from CNV-based genetic association studies. Here we provide a cross-population, microarray-based map of copy-number variant regions (CNVRs) to enable reliable interpretation of CNV association findings. We used the Affymetrix Genome-Wide Human SNP Array 6.0 to scan the genomes of 1167 individuals from two ethnically distinct populations (Europe, N = 717; Rwanda, N = 450). Three different CNV-finding algorithms were tested and compared for sensitivity, specificity, and feasibility. Two algorithms were subsequently used to construct CNVR maps, which were also validated by processing subsamples with additional microarray platforms (Illumina 1M-Duo BeadChip, Nimblegen 385K aCGH array) and by comparing our data with publicly available information. Both algorithms detected a total of 42669 CNVs, 74% of which clustered in 385 CNVRs of a cross-population map. These CNVRs overlap with 862 annotated genes and account for approximately 3.3% of the haploid human genome