Mechanisms of reactivation of latent tuberculosis infection due to SIV coinfection

HIV is a major driver of tuberculosis (TB) reactivation. Depletion of CD4+ T cells is assumed to be the basis behind TB reactivation in individuals with latent tuberculosis infection (LTBI) coinfected with HIV. Nonhuman primates (NHPs) coinfected with a mutant simian immunodeficiency virus (SIVΔGY) that does not cause depletion of tissue CD4+ T cells during infection failed to reactivate TB. To investigate the contribution of CD4+ T cell depletion relative to other mechanisms of SIV-induced reactivation of LTBI, we used CD4R1 antibody to deplete CD4+ T cells in animals with LTBI without lentiviral infection. The mere depletion of CD4+ T cells during LTBI was insufficient in generating reactivation of LTBI. Instead, direct cytopathic effects of SIV resulting in chronic immune activation, along with the altered effector T cell phenotypes and dysregulated T cell homeostasis, were likely mediators of reactivation of LTBI. These results revealed important implications for TB control in HIV-coinfected individuals

Reinspection of a Clinical Proteomics Tumor Analysis Consortium (CPTAC) Dataset with Cloud Computing Reveals Abundant Post-Translational Modifications and Protein Sequence Variants.

The Clinical Proteomic Tumor Analysis Consortium (CPTAC) has provided some of the most in-depth analyses of the phenotypes of human tumors ever constructed. Today, the majority of proteomic data analysis is still performed using software housed on desktop computers which limits the number of sequence variants and post-translational modifications that can be considered. The original CPTAC studies limited the search for PTMs to only samples that were chemically enriched for those modified peptides. Similarly, the only sequence variants considered were those with strong evidence at the exon or transcript level. In this multi-institutional collaborative reanalysis, we utilized unbiased protein databases containing millions of human sequence variants in conjunction with hundreds of common post-translational modifications. Using these tools, we identified tens of thousands of high-confidence PTMs and sequence variants. We identified 4132 phosphorylated peptides in nonenriched samples, 93% of which were confirmed in the samples which were chemically enriched for phosphopeptides. In addition, our results also cover 90% of the high-confidence variants reported by the original proteogenomics study, without the need for sample specific next-generation sequencing. Finally, we report fivefold more somatic and germline variants that have an independent evidence at the peptide level, including mutations in ERRB2 and BCAS1. In this reanalysis of CPTAC proteomic data with cloud computing, we present an openly available and searchable web resource of the highest-coverage proteomic profiling of human tumors described to date

Multivariate analysis of FcR-mediated NK cell functions identifies unique clustering among humans and rhesus macaques

Rhesus macaques (RMs) are a common pre-clinical model used to test HIV vaccine efficacy and passive immunization strategies. Yet, it remains unclear to what extent the Fc-Fc receptor (FcR) interactions impacting antiviral activities of antibodies in RMs recapitulate those in humans. Here, we evaluated the FcR-related functionality of natural killer cells (NKs) from peripheral blood of uninfected humans and RMs to identify intra- and inter-species variation. NKs were screened for FcγRIIIa (human) and FcγRIII (RM) genotypes (FcγRIII(a)), receptor signaling, and antibody-dependent cellular cytotoxicity (ADCC), the latter mediated by a cocktail of monoclonal IgG1 antibodies with human or RM Fc. FcγRIII(a) genetic polymorphisms alone did not explain differences in NK effector functionality in either species cohort. Using the same parameters, hierarchical clustering separated each species into two clusters. Importantly, in principal components analyses, ADCC magnitude, NK contribution to ADCC, FcγRIII(a) cell-surface expression, and frequency of phosphorylated CD3ζ NK cells all contributed similarly to the first principal component within each species, demonstrating the importance of measuring multiple facets of NK cell function. Although ADCC potency was similar between species, we detected significant differences in frequencies of NK cells and pCD3ζ+ cells, level of cell-surface FcγRIII(a) expression, and NK-mediated ADCC (P<0.001), indicating that a combination of Fc-FcR parameters contribute to overall inter-species functional differences. These data strongly support the importance of multi-parameter analyses of Fc-FcR NK-mediated functions when evaluating efficacy of passive and active immunizations in pre- and clinical trials and identifying correlates of protection. The results also suggest that pre-screening animals for multiple FcR-mediated NK function would ensure even distribution of animals among treatment groups in future preclinical trials

Division of Labor

This article describes how dividing a large repetitive task into smaller parts and allocating each to a single person can made tasks simpler, easier to learn, and enabled them to be more quickly carried out. But there are also drawbacks including monotony of work, possible physical injury from task repetition, low flexibility and poor robustness

NUTRITION KNOWLEDGE BETWEEN HEALTH AND NON-HEALTH MAJORS IN COLLEGE-AGED UNDERGRADUATES: A PILOT STUDY

H. Chicoine, K. Hoxie, J. Magana, T. Barron, A. Vahk, K. Taylor Eastern Washington University, Cheney, WA Nutrition is an important aspect in contributing to overall health; however, many individuals have a limited knowledge and/or are misinformed about nutrition. These factors may negatively influence one’s nutrition quality and therefore increase possible health risks. PURPOSE: To examine the general nutrition knowledge between two health majors and two non-health majors in undergraduate students and determine any factors leading to significant differences. METHODS: Researchers distributed the General Nutrition Knowledge Questionnaire obtained from the University College London website and a consent form in health major (Exercise Science and Public Health) courses and non-health major (Marketing and English) courses. Seventy-seven participants completed these four section, 20-minute questionnaires. Additionally, demographic information such as sex, age, weight, height, year in school, and major were collected. Data was analyzed using independent samples t-test with an alpha level set at 0.05. RESULTS: A significant difference was found between health and non-health majors in section 2 (food groups and their nutrients; health; 70.4± 10.9%, non-health; 64.2±10.4%; p=0.013) and section 4 (health problems or diseases related to diet and weight management; health; 72.2±12.8%, non-health;64.1± 14.2%; p=0.011). Health majors scored higher than non-health majors on these two questionnaire sections, but were very similar within the other two sections. Although, females scored higher than males in all four questionnaire sections, this difference was not significant. Additionally, no significant difference was found in body mass index (BMI) between the majors, overall average BMI fell into the overweight category (25.4±5.4 kg/m2) when looking at both majors. CONCLUSIONS: Undergraduate health majors scored significantly higher than non-health majors in questionnaire sections, yet no difference was found in BMI. Therefore, our findings may suggest that although health majors may have a greater understanding about nutrition, the application of this knowledge may be lacking. Study limitations include a larger ratio of females (n=53) to males (n=24), and a large difference in the number of participants representing each year in school