Role of HDAC3 on p53 Expression and Apoptosis in T Cells of Patients with Multiple Sclerosis

Background: Histone deacetylase 3 (HDAC3) belongs to a family of proteins which plays an important role in protein acetylation, chromatin remodeling and transcription of genes, including those that are involved in cell proliferation and cell death. While increased expression of HDAC3 is seen in neoplastic cells, the role of HDAC3 in T cells and their role in autoimmune disease is not known. Methodology/Principal Findings: Applying Affymetrix GeneChip Human Gene 1.0 ST Array and the mixed effects model for gene set analysis, we compared gene expression profiles between multiple sclerosis (MS) patients and healthy controls (HC). Within the Apoptosis_GO gene set, the constitutive expression level of HDAC3 in peripheral blood mononuclear cell (PBMC) was significantly increased in MS patients when compared to controls. Following addition of trichostatin A (TSA), an inhibitor of HDAC3, we examined the expression of p53 by flow cytometry and p53 targeted genes by real time RT-PCR in MS and HC. Culture of PBMC with TSA resulted in increased expression of p53 in HC but not in MS patients. TSA treated T cells from MS patients also showed reduced sensitivity to apoptosis when compared to HC, which was independent of activation of p53 targeted pro-apoptotic genes. Conclusion/Significance: MS patients, when compared to controls, show an increased expression of HDAC3 and relative resistance to TSA induced apoptosis in T cells. Increased expression of HDAC3 in PBMC of MS patients may render putativ

Simulation haute-fidélité et optimisation des pratiques professionnelles. De l'échelon individuel à l'échelle du pôle hospitalier

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High impact of COVID-19 outbreak in a nursing home in the Nouvelle-Aquitaine region, France, March to April 2020

International audienceAbstract Background Elderly people in nursing homes are particularly vulnerable to COVID-19 due to their age, the presence of comorbidities, and community living. On March 14, 2020, at the beginning of the first epidemic wave of COVID-19 in France, a cluster was reported in a nursing home in the Nouvelle-Aquitaine region. We monitored the outbreak as well as the infection prevention and control (IPC) measures implemented. Methods A confirmed case was defined as laboratory-confirmed COVID-19 in a resident or staff member present in the nursing home between March 7 and May 1, 2020; and a probable case as a person presenting an acute respiratory illness after contact with a confirmed case. Symptomatic inpatient residents and symptomatic staff members were systematically tested for SARS-CoV-2. In addition, two screening sessions were held on site. Results We identified 109 cases (98 confirmed, 11 probable). The attack rate was 66% among residents and 45% among staff. Half of all cases were identified during the screening sessions. One-quarter of cases had minor symptoms or were asymptomatic. The case fatality rate among residents was 29%. IPC measures were rapidly implemented such as the quarantine of residents, the reinforcement of staff personal protective equipment, and home quarantine of staff testing positive, which were supplemented in April by systematic controls at the entrance of the nursing home and the creation of additional staff break rooms. Conclusions This outbreak confirmed the considerable health impact of SARS-CoV-2 transmission in a nursing home. In addition to the implementation of IPC measures, the early detection of cases through the screening of residents and staff is essential to identify asymptomatic and pre-symptomatic cases and limit the spread of the virus

Interorgan Coordination of the Murine Adaptive Response to Fasting*

Starvation elicits a complex adaptive response in an organism. No information on transcriptional regulation of metabolic adaptations is available. We, therefore, studied the gene expression profiles of brain, small intestine, kidney, liver, and skeletal muscle in mice that were subjected to 0–72 h of fasting. Functional-category enrichment, text mining, and network analyses were employed to scrutinize the overall adaptation, aiming to identify responsive pathways, processes, and networks, and their regulation. The observed transcriptomics response did not follow the accepted “carbohydrate-lipid-protein” succession of expenditure of energy substrates. Instead, these processes were activated simultaneously in different organs during the entire period. The most prominent changes occurred in lipid and steroid metabolism, especially in the liver and kidney. They were accompanied by suppression of the immune response and cell turnover, particularly in the small intestine, and by increased proteolysis in the muscle. The brain was extremely well protected from the sequels of starvation. 60% of the identified overconnected transcription factors were organ-specific, 6% were common for 4 organs, with nuclear receptors as protagonists, accounting for almost 40% of all transcriptional regulators during fasting. The common transcription factors were PPARα, HNF4α, GCRα, AR (androgen receptor), SREBP1 and -2, FOXOs, EGR1, c-JUN, c-MYC, SP1, YY1, and ETS1. Our data strongly suggest that the control of metabolism in four metabolically active organs is exerted by transcription factors that are activated by nutrient signals and serves, at least partly, to prevent irreversible brain damage

Seasonal variations in the diet and food selection of the Algerian hedgehog Atelerix algirus

International audienceThe Algerian hedgehog Atelerix algirus is an insectivorous species. However, the exact composition of its naturaldiet remains largely undetermined, especially in relation to seasonal variations in food availability. From Marchto November, we simultaneously analysed the composition of 180 hedgehog faecal samples and food availabilityin the Soumman Valley, Algeria to assess food selection in this species. The faeces contained 196 differentprey species, of which 92% belonged to the class Insecta. The highest prey species diversity was found in theColeoptera order (100 species recorded) and the highest species occurrence was found in Hymenoptera (65% of theprey items, mainly represented by the harvester ant Messor barbarus, a crop-ravaging species). This study showsthat the Algerian hedgehog is mainly a generalist species with a diet that is strongly linked to food availability.However, seasonal variations were observed in prey selection, and a notable shift in food preference was observedduring autumn. The exact nature of these changes in feeding behaviour remains to be investigated, notably inrelation to changes in energy requirements of this species before hibernation, in terms of quantity and/or quality