HIV-1 Infection Causes a Down-Regulation of Genes Involved in Ribosome Biogenesis

HIV-1 preferentially infects CD4+ T cells, causing fundamental changes that eventually lead to the release of new viral particles and cell death. To investigate in detail alterations in the transcriptome of the CD4+ T cells upon viral infection, we sequenced polyadenylated RNA isolated from Jurkat cells infected or not with HIV-1. We found a marked global alteration of gene expression following infection, with an overall trend toward induction of genes, indicating widespread modification of the host biology. Annotation and pathway analysis of the most deregulated genes showed that viral infection produces a down-regulation of genes associated with the nucleolus, in particular those implicated in regulating the different steps of ribosome biogenesis, such as ribosomal RNA (rRNA) transcription, pre-rRNA processing, and ribosome maturation. The impact of HIV-1 infection on genes involved in ribosome biogenesis was further validated in primary CD4+ T cells. Moreover, we provided evidence by Northern Blot experiments, that host pre-rRNA processing in Jurkat cells might be perturbed during HIV-1 infection, thus strengthening the hypothesis of a crosstalk between nucleolar functions and viral pathogenesis

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Evo-devo of human adolescence: beyond disease models of early puberty

Despite substantial heritability in pubertal development, much variation remains to be explained, leaving room for the influence of environmental factors to adjust its phenotypic trajectory in the service of fitness goals. Utilizing evolutionary development biology (evo-devo), we examine adolescence as an evolutionary life-history stage in its developmental context. We show that the transition from the preceding stage of juvenility entails adaptive plasticity in response to energy resources, other environmental cues, social needs of adolescence and maturation toward youth and adulthood. Using the evolutionary theory of socialization, we show that familial psychosocial stress fosters a fast life history and reproductive strategy rather than early maturation being just a risk factor for aggression and delinquency. Here we explore implications of an evolutionary-developmental-endocrinological-anthropological framework for theory building, while illuminating new directions for research

Stress factors and stress management interventions: the heuristic of “bottom up” an update from a systematic review

Organizations have increasingly sought to adopt innovative interventions to prevent stress-related issues. In the field of manufacturing, however, the effectiveness of these interventions remains unclear because a systematic and specific review of existing primary evidence has not been undertaken. The present systematic literature review sought to address the foregoing limitation in the literature by summarizing the main source of stress and effectiveness of stress management interventions as grounded in the context of manufacturing. Our review was limited to only randomized clinical trials (RCTs) and quasi-experimental studies and concerned employees from the manufacturing sector. Twenty-two studies on primary, secondary and tertiary interventions across four continents (Asia, Europe, USA and South America) were selected and analyzed in terms of stress factors, methodological properties and outcomes. Most of these were RCT studies (68% Vs 32%) with a majority of secondary interventions (N = 11, 50%), followed by primary (N = 5, 22%), tertiary (N = 3, 13%), and two (9%) mixed interventions. The main outcomes included an improvement of psychological wellbeing, decreased stress reactivity and an increment of general health. There was a predominance of interventions utilizing skills programs and/or cognitive-behavioral techniques. The main source of stress reported related to professional identity, organizational deficiencies, interpersonal conflicts, physical complaints and poor work environment. Taken together, the findings provide important theoretical and practical implications for advancing the study of stress factors and the use of stress management interventions in the workplace. The prerequisite for a successful intervention is to address the real problems experienced by professionals and help them to cope with their difficult situations. The strategy of “bottom-up” offers a potential means of enhancing employees’ health and well-being; however, the most effective means of implementing these interventions needs to be understood better

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

A novel outbred mouse model of 2009 pandemic influenza and bacterial co-infection severity

Influenza viruses pose a significant health risk and annually impose a great cost to patients and the health care system. The molecular determinants of influenza severity, often exacerbated by secondary bacterial infection, are largely unclear. We generated a novel outbred mouse model of influenza virus, Staphylococcus aureus, and coinfection utilizing influenza A/CA/07/2009 virus and S. aureus (USA300). Outbred mice displayed a wide range of pathologic phenotypes following influenza virus or co-infection ranging broadly in severity. Influenza viral burden positively correlated with weight loss although lung histopathology did not. Inflammatory cytokines including IL-6, TNF-α, G-CSF, and CXCL10 positively correlated with both weight loss and viral burden. In S. aureus infection, IL-1β, G-CSF, TNF-α, and IL-6 positively correlated with weight loss and bacterial burden. In co-infection, IL-1β production correlated with decreased weight loss suggesting a protective role. The data demonstrate an approach to identify biomarkers of severe disease and to understand pathogenic mechanisms in pneumonia. © 2013 McHugh et al

Estimating the prevalence of food risk increasing behaviours in UK kitchens

© 2017 Jones et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Foodborne disease poses a serious threat to public health. In the UK, half a million cases are linked to known pathogens and more than half of all outbreaks are associated with catering establishments. The UK Food Standards Agency (FSA) has initiated the UK Food Hygiene Rating Scheme in which commercial food establishments are inspected and scored with the results made public. In this study we investigate the prevalence of food risk increasing behaviours among chefs, catering students and the public. Given the incentive for respondents to misreport when asked about illegal or illicit behaviours we employed a Randomised Response Technique designed to elicit more accurate prevalence rates of such behaviours. We found 14% of the public not always hand-washing immediately after handling raw meat, poultry or fish; 32% of chefs and catering students had worked within 48 hours of suffering from diarrhoea or vomiting. 22% of the public admitted having served meat “on the turn” and 33% of chefs and catering students admitted working in kitchens where such meat was served; 12% of the public and 16% of chefs and catering students admitted having served chicken at a barbeque when not totally sure it was fully cooked. Chefs in fine-dining establishment were less likely to wash their hands after handling meat and fish and those who worked in award winning restaurants were more likely to have returned to work within 48 hours of suffering from diarrhoea and vomiting. We found no correlation between the price of a meal in an establishment, nor its Food Hygiene Rating Score, and the likelihood of any of the food malpractices occurring

Central metabolism in Mycobacterium smegmatis during the transition from O2-rich to O2-poor conditions as studied by isotopomer-assisted metabolite analysis

Isotopomer-assisted metabolite analysis was used to investigate the central metabolism of Mycobacterium smegmatis and its transition from normal growth to a non-replicating state under a hypoxic environment. Tween 80 significantly promoted aerobic growth by improving O2 transfer, while only small amount was degraded and metabolized via the TCA cycle for biomass synthesis. As the bacillus encountered hypoxic stress, isotopomer analysis suggested: (1) isocitrate lyase activity increased, which further induced glyoxylate pathway and glycine dehydrogenase for replenishing NAD+; (2) the relative amount of acetyl-CoA entering the TCA cycle was doubled, whereas little entered the glycolytic and pentose phosphate pathways

Trends of increase in western medical services in traditional medicine hospitals in china

Background: Compare changes in types of hospital service revenues between traditional Chinese medicine (TCM) hospitals and Western-medicine based general hospitals. Methods: 97 TCM hospitals and 103 general hospitals were surveyed in years of 2000 and 2004. Six types of medical service revenue between the two types of hospitals were compared overtime. The national statistics from 1999 to 2008 were also used as complementary evidence. Results: For TCM hospitals, the percentage of service revenue from Western medicine increased from 44.3% to 47.4% while the percentage of service revenue from TCM declined from 26.4% to 18.8% from 1999 to 2004. Percentages of revenue from laboratory tests and surgical procedures for both types of hospitals increased and the discrepancy between the two types of hospitals was narrowed from 1999 to 2004. For TCM hospitals, revenues from laboratory tests increased from 3.64% to 5.06% and revenues from surgical procedures increased from 3.44% to 7.02%. General hospitals\u27 TCM drug revenue in outpatient care declined insignificantly from 5.26% to 3.87%, while the decline for the TCM hospitals was significant from 19.73% to 13.77%. The national statistics from 1999 to 2008 showed similar trends that the percentage of revenue from Western medicine for TCM hospitals increased from 59.6% in 1999 to 62.2% in 2003 and 66.1% in 2008 while the percentage of revenue from TCM for TCM hospitals decreased from 18.0% in 1999, 15.4% in 2003, and 13.7% in 2008. Conclusion: Western medicine has become a vital revenue source for TCM hospitals in the current Chinese health care environment where government subsidies to health care facilities have significantly declined. Policies need to encourage TCM hospitals to identify their own special and effective services, improve public perception, increase demand, strengthen financial sources, and ultimately make contributions to preserving one of the national treasures

What the ‘Moonwalk’ Illusion Reveals about the Perception of Relative Depth from Motion

When one visual object moves behind another, the object farther from the viewer is progressively occluded and/or disoccluded by the nearer object. For nearly half a century, this dynamic occlusion cue has beenthought to be sufficient by itself for determining the relative depth of the two objects. This view is consistent with the self-evident geometric fact that the surface undergoing dynamic occlusion is always farther from the viewer than the occluding surface. Here we use a contextual manipulation ofa previously known motion illusion, which we refer to as the‘Moonwalk’ illusion, to demonstrate that the visual system cannot determine relative depth from dynamic occlusion alone. Indeed, in the Moonwalk illusion, human observers perceive a relative depth contrary to the dynamic occlusion cue. However, the perception of the expected relative depth is restored by contextual manipulations unrelated to dynamic occlusion. On the other hand, we show that an Ideal Observer can determine using dynamic occlusion alone in the same Moonwalk stimuli, indicating that the dynamic occlusion cue is, in principle, sufficient for determining relative depth. Our results indicate that in order to correctly perceive relative depth from dynamic occlusion, the human brain, unlike the Ideal Observer, needs additionalsegmentation information that delineate the occluder from the occluded object. Thus, neural mechanisms of object segmentation must, in addition to motion mechanisms that extract information about relative depth, play a crucial role in the perception of relative depth from motion