Evaluation of a novel quantitative canine species-specific point-of-care assay for C-reactive protein

Background: Species-specific point-of-care tests (POCT) permit a rapid analysis of canine C-reactive protein (CRP), enabling veterinarians to include CRP in clinical decisions. Aim of the study was to evaluate a novel POCT for canine CRP (Point Stripâ TM Canine CRP Assay) run on a small in-house-analyzer (Point Reader TM V) using lithium heparin plasma and to compare assay performance to an already established canine CRP assay (Gentian Canine CRP Immunoassay) run on two different bench top analyzers serving as reference methods (ABX Pentra 400, AU 5800). Linearity was assessed by stepwise dilution of plasma samples with high CRP concentrations. Limit of quantification (LoQ) was determined by repeated measurements of samples with low CRP concentrations. Coefficient of variation (CV) at low (10-50 mg/l), moderate (50-100 mg/l), and high (100-200 mg/l) CRP concentrations was investigated as well as possible interferences. Method comparison study was performed using 45 samples of healthy and diseased dogs. Quality criteria were fulfilled if the total observed error (TEobs=2CV%+bias%) was below the minimal total allowable error of 44.4% (TE min). Additionally, a reference range (n =60 healthy dogs) was established. Results: Linearity was present at CRP concentrations of 10-132 mg/l (&#8793; 361 mg/l CRP with reference method) with a LoQ set at 10 mg/l. At moderate to high CRP concentrations, intra- and inter-assay CVs were< =8% and <=11% respectively, while CVs<=22% and <=28% were present at low concentrations. No interferences were observed at concentrations of 4 g/l hemoglobin, 800 mg/l bilirubin and 8 g/l triglycerides. Method comparison study demonstrated an excellent correlation with both reference methods (r =0.98 for ABX Pentra 400; 0.99 for AU 5800), though revealing a proportional bias of 19.7% (ABX Pentra 400) and 10.7% (AU 5800) respectively. TEobs was 26.7-31.9% and 16.7-21.9% and thus < TEmin. Healthy dogs presented with CRP values <=11.9 mg/l. Conclusions The POCT precisely detects canine CRP at clinically relevant moderate and high CRP concentrations. The assay correlates well with both reference methods. Due to the bias, however, follow-up examinations should be performed with the same assay and analyzer

Computergestützte Analyse und Hit-Songwriting

From USC & GS chart 4273; Surveyed in 1907; Details at Hondagua by Manila R.R. Co

Comparative genomics and transcriptomics of lineages I, II, and III strains of Listeria monocytogenes

BACKGROUND: Listeria monocytogenes is a food-borne pathogen that causes infections with a high-mortality rate and has served as an invaluable model for intracellular parasitism. Here, we report complete genome sequences for two L. monocytogenes strains belonging to serotype 4a (L99) and 4b (CLIP80459), and transcriptomes of representative strains from lineages I, II, and III, thereby permitting in-depth comparison of genome- and transcriptome -based data from three lineages of L. monocytogenes. Lineage III, represented by the 4a L99 genome is known to contain strains less virulent for humans. RESULTS: The genome analysis of the weakly pathogenic L99 serotype 4a provides extensive evidence of virulence gene decay, including loss of several important surface proteins. The 4b CLIP80459 genome, unlike the previously sequenced 4b F2365 genome harbours an intact inlB invasion gene. These lineage I strains are characterized by the lack of prophage genes, as they share only a single prophage locus with other L. monocytogenes genomes 1/2a EGD-e and 4a L99. Comparative transcriptome analysis during intracellular growth uncovered adaptive expression level differences in lineages I, II and III of Listeria, notable amongst which was a strong intracellular induction of flagellar genes in strain 4a L99 compared to the other lineages. Furthermore, extensive differences between strains are manifest at levels of metabolic flux control and phosphorylated sugar uptake. Intriguingly, prophage gene expression was found to be a hallmark of intracellular gene expression. Deletion mutants in the single shared prophage locus of lineage II strain EGD-e 1/2a, the lma operon, revealed severe attenuation of virulence in a murine infection model. CONCLUSION: Comparative genomics and transcriptome analysis of L. monocytogenes strains from three lineages implicate prophage genes in intracellular adaptation and indicate that gene loss and decay may have led to the emergence of attenuated lineages

Microcredit and poverty reduction: a case study of Microfinance Fund for Community Development in Northern Vietnam

Like other developing countries, microcredit in Vietnam has been recognized as an important credit source of the poor, who need capital but are normally by-passed by commercial banks. However, the provision of credit to the poor is challenged by the existing tradeoff between depth of outreach and financial sustainability. In this study, Principal Component Analysis and Propensity Score Matching were used to assess whether microcredit reaches the poor and its role in poverty reduction. The Microfinance Fund and Community Development (MFCD), a microfinance institution in Northern Vietnam was selected as a case study. The research has shown that microcredit successfully reaches the poor households as 67% of credit recipients belong to the last three bottom groups. The observed poverty targeting is consistent with the mission of the microfinance institution. In addition, the provision of microcredit has positive but statistically insignificant impact on household income and expenditure. This study suggests that unless access to additional resources should be made available to the poor, a small amount of credit alone could be insufficient to reduce poverty

Reverse engineering of logic-based differential equation models using a mixed-integer dynamic optimization approach

9 páginas, 6 figuras.-- This is an Open Access article distributed under the terms of the Creative Commons Attribution LicenseMotivation: Systems biology models can be used to test new hypotheses formulated on the basis of previous knowledge or new experimental data, contradictory with a previously existing model. New hypotheses often come in the shape of a set of possible regulatory mechanisms. This search is usually not limited to finding a single regulation link, but rather a combination of links subject to great uncertainty or no information about the kinetic parameters. Results: In this work, we combine a logic-based formalism, to describe all the possible regulatory structures for a given dynamic model of a pathway, with mixed-integer dynamic optimization (MIDO). This framework aims to simultaneously identify the regulatory structure (represented by binary parameters) and the real-valued parameters that are consistent with the available experimental data, resulting in a logic-based differential equation model. The alternative to this would be to perform real-valued parameter estimation for each possible model structure, which is not tractable for models of the size presented in this work. The performance of the method presented here is illustrated with several case studies: a synthetic pathway problem of signaling regulation, a two-component signal transduction pathway in bacterial homeostasis, and a signaling network in liver cancer cellsD.H., J.R.B. and J.S.R. acknowledge funding from the EU FP7 projects ‘NICHE’ (ITN Grant number 289384) and ‘BioPreDyn’ (KBBE grant number 289434). J.R.B. also acknowledges funding from the Spanish Ministerio de Economía y Competitividad (and the FEDER) through the project MultiScales (DPI2011-28112-C04-03).Peer reviewe

Regulation of the transcriptional program by DNA methylation during human αβ T-cell development

© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research. Thymocyte differentiation is a complex process involving well-defined sequential developmental stages that ultimately result in the generation of mature T-cells. In this study, we analyzed DNA methylation and gene expression profiles at successive human thymus developmental stages. Gain and loss of methylation occurred during thymocyte differentiation, but DNA demethylation was much more frequent than de novo methylation and more strongly correlated with gene expression. These changes took place in CpG-poor regions and were closely associated with T-cell differentiation and TCR function. Up to 88 genes that encode transcriptional regulators, some of whose functions in T-cell development are as yet unknown, were differentially methylated during differentiation. Interestingly, no reversion of accumulated DNA methylation changes was observed as differentiation progressed, except in a very small subset of key genes (RAG1, RAG2, CD8A, PTCRA, etc.), indicating that methylation changes are mostly unique and irreversible events. Our study explores the contribution of DNA methylation to T-cell lymphopoiesis and provides a fine-scale map of differentially methylated regions associated with gene expression changes. These can lay the molecular foundations for a better interpretation of the regulatory networks driving human thymopoiesis.Plan Nacional de [I+D+I 2008–2011]; Instituto de Salud Carlos III [grant number PI12/02587]; Red Española de Investigación Renal (REDinREN) [grant number RD12/0021/0018 and RD12/0021/0021]; Spanish Ministry of Science and Innovation [grant number SAF2010- 15106 and PLE2009-0110]; European Union [Fondos FEDER]Peer Reviewe

Sustained release of prostaglandin E2 in fibroblasts expressing ectopically cyclooxygenase 2 impairs P2Y-dependent Ca2+-mobilization

The nucleotide uridine trisphosphate (UTP) released to the extracellular milieu acts as a signaling molecule via activation of specific pyrimidine receptors (P2Y). P2Y receptors are G protein-coupled receptors expressed in many cell types. These receptors mediate several cell responses and they are involved in intracellular calcium mobilization. We investigated the role of the prostanoid PGE2in P2Y signaling in mouse embryonic fibroblasts (MEFs), since these cells are involved in different ontogenic and physiopathological processes, among them is tissue repair following proinflammatory activation. Interestingly, Ca2+-mobilization induced by UTP-dependent P2Y activation was reduced by PGE2when this prostanoid was produced by MEFs transfected with COX-2 or when PGE2was added exogenously to the culture medium. This Ca2+-mobilization was important for the activation of different metabolic pathways in fibroblasts. Moreover, inhibition of COX-2 with selective coxibs prevented UTP-dependent P2Y activation in these cells. The inhibition of P2Y responses by PGE2involves the activation of PKCs and PKD, a response that can be suppressed after pharmacological inhibition of these protein kinases. In addition to this, PGE2reduces the fibroblast migration induced by P2Y-agonists such as UTP. Taken together, these data demonstrate that PGE2is involved in the regulation of P2Y signaling in these cells.This work was supported by Grants BFU2011-24760 and BFU2011-24743 from MINECO, S2010/BMD-2378 from Comunidad de Madrid, Red de Investigación Cardiovascular, RIC, RD12/0042/0019, and Fundación Marcelino Botín (to María Teresa Miras-Portugal). RIC and Ciberehd are funded by the Instituto de Salud Carlos III.Peer Reviewe

Treatment of lactating sows with clofibrate as a synthetic agonist of PPARalpha does not influence milk fat content and gains of litters

BACKGROUND: In rats, it has been observed that treatment with activators of peroxisome proliferator-activated receptor a (PPARalpha) disturbs metabolic adaptations during lactation, which in turn lead to a reduction of milk fat content and gains of litters during the suckling period. It has not yet been investigated whether agonists of PPARalpha are impairing milk production of lactating sows in a similar manner as in rats. Therefore, the present study aimed to investigate the effect of treatment with clofibrate, a strong synthetic agonist of PPARalpha, on milk composition and litter gains in lactating sows. RESULTS: Twenty lactating sows received either a basal diet (control group) or the same diet with supplementation of 2 g of clofibrate per kg of diet (clofibrate group). In the clofibrate group, mRNA concentrations of various PPARalpha target genes involved in fatty acid utilization in liver and skeletal muscle were moderately up-regulated. Fat and energy content of the milk and gains of litters during the suckling period were not different between the control group and the clofibrate group. CONCLUSIONS: It is shown that treatment with clofibrate induces only a moderate up-regulation of PPARalpha target genes in liver and muscle of lactating sows and in turn might have limited effect on whole body fatty acid utilization. This may be the reason why clofibrate treatment did not influence milk fat content and gains of litters during the suckling period. Thus, the present study indicates that activation of PPARalpha induced either by native agonists such as dietary polyunsaturated fatty acids or a by negative energy balance might be largely uncritical in lactating sows with respect to milk production and litter gains in lactating sows

Neuorientierung der Agrar- und Ernährungswirtschaft in der Ukraine

Die Tätigkeitsschwerpunkte der Sektion 2 des Zentrums für internationale Entwicklungs- und Umweltforschung (ZEU) – zusammengefasst unter dem vereinigenden Titel „Ernährungssicherung“ – widmen sich der aktuellen Ernährungssituation von Menschen sowie den wirtschaftlichen Rahmenbedingungen von Ländern und Regionen zur Gewährleistung von Nahrungs- und Ernährungssicherheit. Dabei haben wir es uns zur Aufgabe gemacht, unsere wissenschaftliche Forschung als Mittelpunkt der Sektionsarbeit durch weitere Maßnahmen zu flankieren, wie beispielsweise Beratung und Weiterbildung, mit denen wir aktiv einen Beitrag zur Ernährungssicherung leisten können