Protection from Alzheimer's-like disease in the mouse by genetic ablation of inducible nitric oxide synthase

Brains from subjects who have Alzheimer's disease (AD) express inducible nitric oxide synthase (iNOS). We tested the hypothesis that iNOS contributes to AD pathogenesis. Immunoreactive iNOS was detected in brains of mice with AD-like disease resulting from transgenic expression of mutant human β-amyloid precursor protein (hAPP) and presenilin-1 (hPS1). We bred hAPP-, hPS1-double transgenic mice to be iNOS+/+ or iNOS−/−, and compared them with a congenic WT strain. Deficiency of iNOS substantially protected the AD-like mice from premature mortality, cerebral plaque formation, increased β-amyloid levels, protein tyrosine nitration, astrocytosis, and microgliosis. Thus, iNOS seems to be a major instigator of β-amyloid deposition and disease progression. Inhibition of iNOS may be a therapeutic option in AD

Plasma Metabolomics in Human Pulmonary Tuberculosis Disease: A Pilot Study

We aimed to characterize metabolites during tuberculosis (TB) disease and identify new pathophysiologic pathways involved in infection as well as biomarkers of TB onset, progression and resolution. Such data may inform development of new anti-tuberculosis drugs. Plasma samples from adults with newly diagnosed pulmonary TB disease and their matched, asymptomatic, sputum culture-negative household contacts were analyzed using liquid chromatography high-resolution mass spectrometry (LC-MS) to identify metabolites. Statistical and bioinformatics methods were used to select accurate mass/charge (m/z) ions that were significantly different between the two groups at a false discovery rate (FDR) of q<0.05. Two-way hierarchical cluster analysis (HCA) was used to identify clusters of ions contributing to separation of cases and controls, and metabolomics databases were used to match these ions to known metabolites. Identity of specific D-series resolvins, glutamate and Mycobacterium tuberculosis (Mtb)-derived trehalose-6-mycolate was confirmed using LC-MS/MS analysis. Over 23,000 metabolites were detected in untargeted metabolomic analysis and 61 metabolites were significantly different between the two groups. HCA revealed 8 metabolite clusters containing metabolites largely upregulated in patients with TB disease, including anti-TB drugs, glutamate, choline derivatives, Mycobacterium tuberculosis-derived cell wall glycolipids (trehalose-6-mycolate and phosphatidylinositol) and pro-resolving lipid mediators of inflammation, known to stimulate resolution, efferocytosis and microbial killing. The resolvins were confirmed to be RvD1, aspirin-triggered RvD1, and RvD2. This study shows that high-resolution metabolomic analysis can differentiate patients with active TB disease from their asymptomatic household contacts. Specific metabolites upregulated in the plasma of patients with active TB disease, including Mtb-derived glycolipids and resolvins, have potential as biomarkers and may reveal pathways involved in TB disease pathogenesis and resolution

Use of a Molecular Diagnostic Test in AFB Smear Positive Tuberculosis Suspects Greatly Reduces Time to Detection of Multidrug Resistant Tuberculosis

Background: The WHO has recommended the implementation of rapid diagnostic tests to detect and help combat M/XDR tuberculosis (TB). There are limited data on the performance and impact of these tests in field settings. Methods: The performance of the commercially available Genotype MTBDRplus molecular assay was compared to conventional methods including AFB smear, culture and drug susceptibility testing (DST) using both an absolute concentration method on Löwenstein-Jensen media and broth-based method using the MGIT 960 system. Sputum specimens were obtained from TB suspects in the country of Georgia who received care through the National TB Program. Results: Among 500 AFB smear-positive sputum specimens, 458 (91.6%) had both a positive sputum culture for Mycobacterium tuberculosis and a valid MTBDRplus assay result. The MTBDRplus assay detected isoniazid (INH) resistanc

Praktyczna metoda analizy ortogonalnych płyt z uwzględnieniem schematu statycznego, warunków brzegowych i obciążenia

Is stated practical method for analysis of orthogonal plates with consideration of specific model of design diagram, boundary conditions and loading. For illustration of offered method are considered specific examples: applied in the center pinning on all four sides plate, when is constant, all four sides of plate are rigidly attached and on them is applied uniformly distributed constant loading.W artykule przedstawiono metodę analizy ortogonalnych płyt, która ma zastosowanie praktyczne. Metoda projektowania polega na analizie schematu statycznego, warunków brzegowych i obciążeń. W celu zilustrowania metody przedstawiono przykłady obliczeniowe. Pierwszy dotyczy płyty opartej swobodnie na wszystkich czterech krawędziach, obciążonej siłą skupioną pośrodku, natomiast drugi dotyczy płyty zamocowanej sztywno oraz obciążonej obciążeniem równomiernie rozłożonym

Young children's evaluations of the ingroup and of outgroups: A multi-national study

In investigating intergroup attitudes, previous research in developmental psychology has frequently confounded ingroup favouritism and outgroup derogation. The present study, using unconfounded measures, examines the possibility that ingroup favouritism and outgroup derogation are distinct phenomena. Six-year-old children (n=594) from five, culturally diverse nations were asked to make various evaluations of the national ingroup and of four national outgroups. The data indicate that although there is overwhelming evidence that young children favour the ingroup over other groups, outgroup derogation is limited in extent and appears to reproduce attitudes held by adult members of the particular nations investigated