Krpeljska fauna autohtone pramenke u Istočnoj Srbiji

Sheep production is an example of a sustainable production fully integrated within the local rural development. One of the main threats on the outdoor breeding of sheep is parasitism. Ticks are nuisances and vectors of several diseases agents. The distribution of ticks appears to be changing, with spread to previously unaffected areas. Tick and tick-borne disease control is one of the major components of animal health program protecting livestock in the developing countries, which reflects impact on the livelihood of resource-poor farming communities. Taking into consideration the negative impact on the health status of the livestock, also the direct and indirect economic losses, it is necessary to examine the tolerance and resistance of certain species against diseases. It is one of the most important elements of the strategy of selection and screening for resistant animals. The aim of this study was to determine the tick species persisting in 45 tested autochthonous Zackel sheep flocks, and examine their seasonal occurrence from March 2010 to January 2011, in the region of South Serbia. The result showed that Ixodes, Dermacentor, Ripicephalus and Haemaphysalis were the most abundant ticks found, affecting 50.40% tested sheep. The result of this study is a survey of tick species from autochthonous Zackel sheep in Serbia and implication of possible preventions measures for diseases caused and transmitted by ticks.Ovčarstvo predstavlja primer održive proizvodnje koja čini sastavni deo ruralnog razvoja. Jedan od glavnih zdravstvenih problema kod ekstenzivnog načina uzgoja ovaca predstavljaju parazitske infekcije. Krpelji su vektori za uzročnike mnogobrojnih oboljenja. Rasprostranjenost krpelja se menja i u novije vreme ih nalazimo i na novim arealima. U zemljama u razvoju, borba protiv krpelja i oboljenja prenosica krpeljima predstavljaju jedan od glavnih strateških tačaka zdravstvenog nadzora nad životinjama i ljudima. Uzimajući u obzir značaj direktnih i indirektnih ekonomskih gubitaka izazvanih krpeljima i oboljenjima čiji su oni uzročnici, posebna pažnja treba da se posveti ispitivanju tolerancije i otpornosti ka parazitskim bolestima pojedinih vrsta i rasa životinja. Potraga za otpornim jedinkama i njihova selekcija treba da bude deo strategije stočarstva. Cilj ovog rada je bio da prikaže rezultate ispitivanja o prisustvu krpeljske faune u 45 zapata ovaca autohtone pramenke. Ispitana je sezonalna distribucija pojave pojedinih krpelja u periodu između marta 2010. i januara 2011. godine, u regionu Istočne Srbije. Kod 50, 40% ispitanih ovaca ustanovljeno je prisustvo krpelja. Rezultati pokazuju da su krpelji iz rodova Ixodes, Dermacentor, Ripicephalus i Haemaphysalis najučestaliji u zapatima ovaca autohtone pramenke

Efficacy and safety of a novel oral isoxazoline, sarolaner (Simparica™), for the treatment of sarcoptic mange in dogs

AbstractThe efficacy of the novel isoxazoline, sarolaner (Simparica™) was investigated in dogs with clinical signs consistent with sarcoptic mange and harbouring natural infestations of Sarcoptes scabiei. One placebo-controlled laboratory study and one multi-centred field study with a commercial comparator containing imidacloprid/moxidectin (Advocate® spot-on) were conducted. Oral or topical treatments were administered on Days 0 and 30. Up to 10 skin scrapings were taken for the assessment of S. scabiei infestations from each dog before treatment and on Days 14, 30, 44 and 60 in the laboratory study, and on Days 30 and 60 in the field study. In the laboratory study, efficacy was calculated based on the percent reduction of mean live mite counts compared to the placebo group. In the field study parasitological cure rate (% dogs free of mites) was determined and non-inferiority of sarolaner to the control product was assessed.In the laboratory study 44 mixed breed dogs were enrolled in four batches. Due to decreasing mite counts in the placebo treated dogs, immunosuppression with dexamethasone (0.4mg/kg three times per week for two weeks) was initiated in all dogs on study at that time (n=6) and those subsequently enrolled (n=14). In the field study, dogs were enrolled in a 2:1 ratio (sarolaner:comparator); 79 dogs were assessed for efficacy and safety, and an additional 45 dogs were assessed for safety only. There were no treatment related adverse events in either study.In the laboratory study, no mites were found on any sarolaner-treated dogs 14 days after the first treatment except for one dog that had a single mite on Day 44. In the field study, the parasitological cure rate was 88.7% and 100% in the sarolaner group and 84.6% and 96.0% in the imidacloprid/moxidectin group, on Days 30 and 60, respectively. Statistical analysis showed that sarolaner was non-inferior to imidacloprid/moxidectin at both time points. The clinical signs of sarcoptic mange, including hair loss, papules, pruritus, erythema, and scaling/crusting improved throughout the study.Sarolaner was safe, achieved 100% reduction in the numbers of S. scabiei detected and resulted in marked improvement of the clinical signs of sarcoptic mange in dogs following two monthly oral administrations

Transcriptional Autoregulatory Loops Are Highly Conserved in Vertebrate Evolution

BACKGROUND: Feedback loops are the simplest building blocks of transcriptional regulatory networks and therefore their behavior in the course of evolution is of prime interest. METHODOLOGY: We address the question of enrichment of the number of autoregulatory feedback loops in higher organisms. First, based on predicted autoregulatory binding sites we count the number of autoregulatory loops. We compare it to estimates obtained either by assuming that each (conserved) gene has the same chance to be a target of a given factor or by assuming that each conserved sequence position has an equal chance to be a binding site of the factor. CONCLUSIONS: We demonstrate that the numbers of putative autoregulatory loops conserved between human and fugu, danio or chicken are significantly higher than expected. Moreover we show, that conserved autoregulatory binding sites cluster close to the factors' starts of transcription. We conclude, that transcriptional autoregulatory feedback loops constitute a core transcriptional network motif and their conservation has been maintained in higher vertebrate organism evolution

The interplay of intrinsic and extrinsic bounded noises in genetic networks

After being considered as a nuisance to be filtered out, it became recently clear that biochemical noise plays a complex role, often fully functional, for a genetic network. The influence of intrinsic and extrinsic noises on genetic networks has intensively been investigated in last ten years, though contributions on the co-presence of both are sparse. Extrinsic noise is usually modeled as an unbounded white or colored gaussian stochastic process, even though realistic stochastic perturbations are clearly bounded. In this paper we consider Gillespie-like stochastic models of nonlinear networks, i.e. the intrinsic noise, where the model jump rates are affected by colored bounded extrinsic noises synthesized by a suitable biochemical state-dependent Langevin system. These systems are described by a master equation, and a simulation algorithm to analyze them is derived. This new modeling paradigm should enlarge the class of systems amenable at modeling. We investigated the influence of both amplitude and autocorrelation time of a extrinsic Sine-Wiener noise on: $(i)$ the Michaelis-Menten approximation of noisy enzymatic reactions, which we show to be applicable also in co-presence of both intrinsic and extrinsic noise, $(ii)$ a model of enzymatic futile cycle and $(iii)$ a genetic toggle switch. In $(ii)$ and $(iii)$ we show that the presence of a bounded extrinsic noise induces qualitative modifications in the probability densities of the involved chemicals, where new modes emerge, thus suggesting the possibile functional role of bounded noises

Strong negative self regulation of Prokaryotic transcription factors increases the intrinsic noise of protein expression

Background Many prokaryotic transcription factors repress their own transcription. It is often asserted that such regulation enables a cell to homeostatically maintain protein abundance. We explore the role of negative self regulation of transcription in regulating the variability of protein abundance using a variety of stochastic modeling techniques. Results We undertake a novel analysis of a classic model for negative self regulation. We demonstrate that, with standard approximations, protein variance relative to its mean should be independent of repressor strength in a physiological range. Consequently, in that range, the coefficient of variation would increase with repressor strength. However, stochastic computer simulations demonstrate that there is a greater increase in noise associated with strong repressors than predicted by theory. The discrepancies between the mathematical analysis and computer simulations arise because with strong repressors the approximation that leads to Michaelis-Menten-like hyperbolic repression terms ceases to be valid. Because we observe that strong negative feedback increases variability and so is unlikely to be a mechanism for noise control, we suggest instead that negative feedback is evolutionarily favoured because it allows the cell to minimize mRNA usage. To test this, we used in silico evolution to demonstrate that while negative feedback can achieve only a modest improvement in protein noise reduction compared with the unregulated system, it can achieve good improvement in protein response times and very substantial improvement in reducing mRNA levels. Conclusions Strong negative self regulation of transcription may not always be a mechanism for homeostatic control of protein abundance, but instead might be evolutionarily favoured as a mechanism to limit the use of mRNA. The use of hyperbolic terms derived from quasi-steady-state approximation should also be avoided in the analysis of stochastic models with strong repressors

Modelling of the regulation of the hilA promoter of type three secretion system of Salmonella enterica serovar Typhimurium

One of the most common modes of secretion of toxins in gram-negative bacteria is via the type three secretion system (TTSS), which enables the toxins to be specifically exported into the host cell. The hilA gene product is a key regulator of the expression of the TTSS located on the pathogenicity island (SPI-1) of Salmonella enterica serovar Typhimurium. It has been proposed earlier that the regulation of HilA expression is via a complex feedforward loop involving the transactivators HilD, HilC and RtsA. In this paper, we have constructed a mathematical model of regulation of hilA-promoter by all the three activators using two feedforward loops. We have modified the model to include additional complexities in regulation such as the proposed positive feedback and cross regulations of the three transactivators. Results of the various models indicate that the basic model involving two Type I coherent feedforward loops with an OR gate is sufficient to explain the published experimental observations. We also discuss two scenarios where the regulation can occur via monomers or heterodimers of the transactivators and propose experiments that can be performed to distinguish the two modes of regulator function

Regulatory control and the costs and benefits of biochemical noise

Experiments in recent years have vividly demonstrated that gene expression can be highly stochastic. How protein concentration fluctuations affect the growth rate of a population of cells, is, however, a wide open question. We present a mathematical model that makes it possible to quantify the effect of protein concentration fluctuations on the growth rate of a population of genetically identical cells. The model predicts that the population's growth rate depends on how the growth rate of a single cell varies with protein concentration, the variance of the protein concentration fluctuations, and the correlation time of these fluctuations. The model also predicts that when the average concentration of a protein is close to the value that maximizes the growth rate, fluctuations in its concentration always reduce the growth rate. However, when the average protein concentration deviates sufficiently from the optimal level, fluctuations can enhance the growth rate of the population, even when the growth rate of a cell depends linearly on the protein concentration. The model also shows that the ensemble or population average of a quantity, such as the average protein expression level or its variance, is in general not equal to its time average as obtained from tracing a single cell and its descendants. We apply our model to perform a cost-benefit analysis of gene regulatory control. Our analysis predicts that the optimal expression level of a gene regulatory protein is determined by the trade-off between the cost of synthesizing the regulatory protein and the benefit of minimizing the fluctuations in the expression of its target gene. We discuss possible experiments that could test our predictions.Comment: Revised manuscript;35 pages, 4 figures, REVTeX4; to appear in PLoS Computational Biolog

Stochastic signalling rewires the interaction map of a multiple feedback network during yeast evolution

During evolution, genetic networks are rewired through strengthening or weakening their interactions to develop new regulatory schemes. In the galactose network, the GAL1/GAL3 paralogues and the GAL2 gene enhance their own expression mediated by the Gal4p transcriptional activator. The wiring strength in these feedback loops is set by the number of Gal4p binding sites. Here we show using synthetic circuits that multiplying the binding sites increases the expression of a gene under the direct control of an activator, but this enhancement is not fed back in the circuit. The feedback loops are rather activated by genes that have frequent stochastic bursts and fast RNA decay rates. In this way, rapid adaptation to galactose can be triggered even by weakly expressed genes. Our results indicate that nonlinear stochastic transcriptional responses enable feedback loops to function autonomously, or contrary to what is dictated by the strength of interactions enclosing the circuit

Modeling stochasticity and robustness in gene regulatory networks

Motivation: Understanding gene regulation in biological processes and modeling the robustness of underlying regulatory networks is an important problem that is currently being addressed by computational systems biologists. Lately, there has been a renewed interest in Boolean modeling techniques for gene regulatory networks (GRNs). However, due to their deterministic nature, it is often difficult to identify whether these modeling approaches are robust to the addition of stochastic noise that is widespread in gene regulatory processes. Stochasticity in Boolean models of GRNs has been addressed relatively sparingly in the past, mainly by flipping the expression of genes between different expression levels with a predefined probability. This stochasticity in nodes (SIN) model leads to over representation of noise in GRNs and hence non-correspondence with biological observations

Tick fauna of the autochthonous Zackel sheep in South Serbia region

Sheep production is an example of a sustainable production fully integrated within the local rural development. One of the main threats on the outdoor breeding of sheep is parasitism. Ticks are nuisances and vectors of several diseases agents. The distribution of ticks appears to be changing, with spread to previously unaffected areas. Tick and tick-borne disease control is one of the major components of animal health program protecting livestock in the developing countries, which reflects impact on the livelihood of resource-poor farming communities. Taking into consideration the negative impact on the health status of the livestock, also the direct and indirect economic losses, it is necessary to examine the tolerance and resistance of certain species against diseases. It is one of the most important elements of the strategy of selection and screening for resistant animals. The aim of this study was to determine the tick species persisting in 45 tested autochthonous Zackel sheep flocks, and examine their seasonal occurrence from March 2010 to January 2011, in the region of South Serbia. The result showed that Ixodes, Dermacentor, Ripicephalus and Haemaphysalis were the most abundant ticks found, affecting 50.40% tested sheep. The result of this study is a survey of tick species from autochthonous Zackel sheep in Serbia and implication of possible preventions measures for diseases caused and transmitted by ticks