DIFFERENCES IN IMPULSIVITY BETWEEN HIGH-ALCOHOL PREFERRING AND LOW-ALCOHOL PREFERRING MICE IN A DRL TASK

poster abstractHigh impulsivity, the propensity to prefer small immediate rewards to larger delayed rewards, is more observable in alcoholics as well as drug addicts than in non-addicts. However, it remains unclear whether impulsivity precedes and potentially causes substance use disorders. Of particular interest to us is whether the high drinkers differ from low drinkers in their ability to perceive time. In this study we examine differences in impulsivity, as measured by a differential reinforcement of low rates of responding (DRL) task, in mice selectively bred for differences in alcohol consumption, High Alcohol Preferring (HAP-II) and Low Alcohol Preferring (LAP-II) mice. In this task, subjects must inhibit instrumental behavior until an unsignaled DRL interval has elapsed. We hypothesize that due to their previously demonstrated impulsivity, the HAPII mice will perform poorly and receive fewer rewards than LAPII mice. We expect that our results will indicate that due to premature responding, HAPII mice will receive fewer rewards than LAPII mice during the DRL task, but obtain more rewards during a basic fixed interval task, when early responding is not punished. Therefore, alcohol naive HAPII mice will be more impulsive than LAPII mice, as measured by the DRL task. This finding suggests impulsivity is a heritable endophenotype that precedes exposure to alcoholism or drugs

Perspectives on the Trypanosoma cruzi-host cell receptor interaction

Chagas disease is caused by the parasite Trypanosoma cruzi. The critical initial event is the interaction of the trypomastigote form of the parasite with host receptors. This review highlights recent observations concerning these interactions. Some of the key receptors considered are those for thromboxane, bradykinin, and for the nerve growth factor TrKA. Other important receptors such as galectin-3, thrombospondin, and laminin are also discussed. Investigation into the molecular biology and cell biology of host receptors for T. cruzi may provide novel therapeutic targets

Polarization of TH2 response is decreased during pregnancy in systemic lupus erythematosus

This study evaluated some cytokines involved in the Th1-Th2 shift during pregnancy in patients with systemic lupus erythematosus (SLE) and healthy women. Twenty-seven consecutive successful pregnancies in 26 SLE patients and 28 pregnancies in 28 matched healthy subjects, as controls, were enrolled and prospectively studied. Sera obtained at first and third trimesters of pregnancy were tested for IL-1α, IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12p70, INF-γ, and TNF-α with a highly sensitive, multiplexed sandwich ELISA (SearchLight Human Inflammatory Cytokine Array). Statistics were performed by SPSS package. IL-8 serum levels were higher in the first (P<0.0001) and third (P=0.003) trimesters of pregnancy in SLE patients compared with controls, INF-γ serum levels in the third trimester (P=0.009), and IL-10 serum levels in the first and third trimesters (P=0.055 and P<0.0001, respectively). IL-2 (r=0.524 P=0.010), IL-12 (r=0.549 P=0.007), IFN-γ (r=0.492 P=0.017), and IL-6 (r=0.515 P=0.020) serum levels correlated with disease activity in SLE patients in the first trimester of pregnancy. Cytokine profile was similar in patients with and without lupus nephritis both in the first and in the third trimesters of pregnancy. IL-8 serum levels were lower in patients with a previous diagnosis of antiphospholipid antibody syndrome compared with those without, both in the first and in the third trimesters of pregnancy. In SLE patients, a lower than expected decrease in Th1 cytokine serum levels was observed in the third trimester of gestation which could contribute to a lower Th2 cytokine polarization during pregnancy

Detection of serum anti-B/B' UsnRNP antibodies in patients with connective tissue diseases by immunoblotting

Objective: To investigate the reliability of the immunoblot method in the detection of serum immunoreactivity towards the B/B' polypeptides of U small nuclear ribonucleoproteins (UsnRNP) and to assess the significance of these antibodies in connective tissue disease (CTD) patients. Methods: We tested the sera of 348 patients with CTD (101 SLE, 51 systemic sclerosis, 53 primary Sjogren's syndrome, 27 poly/dermatomyositis, 15 rheumatoid arthritis and 101 overlap CTD), of 31 matched healthy subjects and 13 patients with primary Epstein-Barr virus (EBV) infection with high titre IgG anti-EBV antibodies. IgG anti-UsnRNP antibodies were determined by immunoblotting on nuclear extract from Raji cells (an EBV-immortalised human B lymphoid cell line) and Jurkat cells (a human T lymphoid cell line). Anti-dsDNA antibodies were detected by indirect immunofluorescence on Crithidia luciliae and anti-ENA by counterimmunoelectrophoresis. Anti-dsDNA activity and avidity were measured in SLE sera by ELISA with Scatchard analysis. Results were statistically analysed by chi-square and Mann-Whitney tests. Results: A high frequency of anti-B/B' antibodies was found in the sera of CTD patients, confined to SLE (54.4%) and overlap CTD with SLE features (55,2%). Anti-B/B' immune reactivity was closely associated with other anti-UsnRNP specificities, gel precipitating anti-nRNP and anti-P antibodies. Nine out of 15 (60%) anti-B/B' positive/anti-ENA negative lupus sera on Raji blots were confirmed to be positive also on Jurkat blots. The sera from patients with EBV infection provided, on Raji blots, completely different band patterns from those obtained with auto-immune sera. Conclusions. The Sm B/B' proteins are the predominant or, at least, the most frequently targeted antigens of the UsnRNP auto-immune response in SLE and "lupus-like" overlap CTD. Moreover, anti-B/B' is diagnostically specific for CTD with SLE features. Immunoblotting on human B lymphoid cells is a reliable method, in terms of sensitivity and specificity, for the detection of anti-Sm B/B' antibodies

QuantiMus: A Machine Learning-Based Approach for High Precision Analysis of Skeletal Muscle Morphology.

Skeletal muscle injury provokes a regenerative response, characterized by the de novo generation of myofibers that are distinguished by central nucleation and re-expression of developmentally restricted genes. In addition to these characteristics, myofiber cross-sectional area (CSA) is widely used to evaluate muscle hypertrophic and regenerative responses. Here, we introduce QuantiMus, a free software program that uses machine learning algorithms to quantify muscle morphology and molecular features with high precision and quick processing-time. The ability of QuantiMus to define and measure myofibers was compared to manual measurement or other automated software programs. QuantiMus rapidly and accurately defined total myofibers and measured CSA with comparable performance but quantified the CSA of centrally-nucleated fibers (CNFs) with greater precision compared to other software. It additionally quantified the fluorescence intensity of individual myofibers of human and mouse muscle, which was used to assess the distribution of myofiber type, based on the myosin heavy chain isoform that was expressed. Furthermore, analysis of entire quadriceps cross-sections of healthy and mdx mice showed that dystrophic muscle had an increased frequency of Evans blue dye+ injured myofibers. QuantiMus also revealed that the proportion of centrally nucleated, regenerating myofibers that express embryonic myosin heavy chain (eMyHC) or neural cell adhesion molecule (NCAM) were increased in dystrophic mice. Our findings reveal that QuantiMus has several advantages over existing software. The unique self-learning capacity of the machine learning algorithms provides superior accuracy and the ability to rapidly interrogate the complete muscle section. These qualities increase rigor and reproducibility by avoiding methods that rely on the sampling of representative areas of a section. This is of particular importance for the analysis of dystrophic muscle given the "patchy" distribution of muscle pathology. QuantiMus is an open source tool, allowing customization to meet investigator-specific needs and provides novel analytical approaches for quantifying muscle morphology

Herramientas moleculares aplicadas al estudio de aguas para el consumo humano, comunidad El Cacao, Nicaragua

Se determinó la presencia de contaminantes microbianos en aguas de consumo humano de la comunidad El Cacao, Mosonte, Nueva Segovia. El análisis se realizó tanto por métodos microbiológicos como por ví­a molecular analizando su interrelación con las enfermedades que se observan en la comunidad. Se obtuvo la presencia de coliformes fecales, totales y Escherichia coli desde la captación hasta el tanque de almacenamiento. Los aislados identificados pertenecen a las bacterias del tipo Alcaligenes y Paenalcaligenes, además de Stenotrophomonas y Serratia. Las cuales son bacterias acuáticas y están asociadas a diversas enfermedades. Además se identificó lapresencia de Aspergillus que han sido bien reportados en diversas enfermedades humanas

Diagnostic efficacy of the ELISA test for the detection of deamidated anti-gliadin peptide antibodies in the diagnosis and monitoring of celiac disease

Volcano plot of differential gene expression in IZE_Suc vs IZE, ZE_5w vs IZE_Suc and SE_5w vs IZE. (DOCX 256 kb

Genome-Scale CRISPR-Mediated Control of Gene Repression and Activation

While the catalog of mammalian transcripts and their expression levels in different cell types and disease states is rapidly expanding, our understanding of transcript function lags behind. We present a robust technology enabling systematic investigation of the cellular consequences of repressing or inducing individual transcripts. We identify rules for specific targeting of transcriptional repressors (CRISPRi), typically achieving 90%–99% knockdown with minimal off-target effects, and activators (CRISPRa) to endogenous genes via endonuclease-deficient Cas9. Together they enable modulation of gene expression over a ∼1,000-fold range. Using these rules, we construct genome-scale CRISPRi and CRISPRa libraries, each of which we validate with two pooled screens. Growth-based screens identify essential genes, tumor suppressors, and regulators of differentiation. Screens for sensitivity to a cholera-diphtheria toxin provide broad insights into the mechanisms of pathogen entry, retrotranslocation and toxicity. Our results establish CRISPRi and CRISPRa as powerful tools that provide rich and complementary information for mapping complex pathways