Cell autonomous regulation of herpes and influenza virus infection by the circadian clock.

Viruses are intracellular pathogens that hijack host cell machinery and resources to replicate. Rather than being constant, host physiology is rhythmic, undergoing circadian (∼24 h) oscillations in many virus-relevant pathways, but whether daily rhythms impact on viral replication is unknown. We find that the time of day of host infection regulates virus progression in live mice and individual cells. Furthermore, we demonstrate that herpes and influenza A virus infections are enhanced when host circadian rhythms are abolished by disrupting the key clock gene transcription factor Bmal1. Intracellular trafficking, biosynthetic processes, protein synthesis, and chromatin assembly all contribute to circadian regulation of virus infection. Moreover, herpesviruses differentially target components of the molecular circadian clockwork. Our work demonstrates that viruses exploit the clockwork for their own gain and that the clock represents a novel target for modulating viral replication that extends beyond any single family of these ubiquitous pathogens.A.B.R. acknowledges funding from the Wellcome Trust (083643/Z/07/Z, 100333/Z/12/Z and 100574/Z/12/Z), the European Research Council (ERC Starting Grant No. 281348, MetaCLOCK), the EMBO Young Investigators Programme, the Lister Institute of Preventative Medicine and the Medical Research Council (MRC_MC_UU_12012/5). A.D.N acknowledges funding from the People Programme (Marie Curie Actions) of the European Union Seventh Framework Programme (FP7/2007-2013; REA grant agreement 627630). We thank L. Ansel-Bollepalli for assistance with animal breeding, I. Robinson for assistance with pilot animal experiments, A. Snijders and H. Flynn (Francis Crick Institute Proteomics Core) for help with proteomics work, Cambridge NIHR BRC Cell Phenotyping Hub for flow cytometry assistance, A. Miyawaki (RIKEN Brain Science Institute, Japan) for Fucci2 lentiviral vectors, and H. Coleman, J. May and M. Jain for helpful discussions. We thank Prof J. Bass (Northwestern University, USA) for Bmal-/- mouse embryonic fibroblasts used in preliminary experiments, and N. Heaton and P. Palese (Icahn School of Medicine at Mount Sinai, USA) for PB2::Gaussia luciferase IAV (PR8 PB2::GLUC).This is the author accepted manuscript. The final version is available from the National Academy of Sciences via http://dx.doi.org/10.1073/pnas.160189511

Demanda de carnes certificadas de origem taurina no Rio Grande do Sul: uma visão das associações de raças.

O estudo tem como objetivo investigar a demanda de carnes certificadas no RS sob o ponto de vista das associações de raças.Claudia Cristina Gulias Gomes, editora técnica

The Pentose Phosphate Pathway Regulates the Circadian Clock

The circadian clock is a ubiquitous timekeeping system that organizes the behavior and physiology of organisms over the day and night. Current models rely on transcriptional networks that coordinate circadian gene expression of thousands of transcripts. However, recent studies have uncovered phylogenetically conserved redox rhythms that can occur independently of transcriptional cycles. Here we identify the pentose phosphate pathway (PPP), a critical source of the redox cofactor NADPH, as an important regulator of redox and transcriptional oscillations. Our results show that genetic and pharmacological inhibition of the PPP prolongs the period of circadian rhythms in human cells, mouse tissues, and fruit flies. These metabolic manipulations also cause a remodeling of circadian gene expression programs that involves the circadian transcription factors BMAL1 and CLOCK, and the redox-sensitive transcription factor NRF2. Thus, the PPP regulates circadian rhythms via NADPH metabolism, suggesting a pivotal role for NADPH availability in circadian timekeeping.Peer reviewe

Integrated high-content quantification of intracellular ROS levels and mitochondrial morphofunction

Oxidative stress arises from an imbalance between the production of reactive oxygen species (ROS) and their removal by cellular antioxidant systems. Especially under pathological conditions, mitochondria constitute a relevant source of cellular ROS. These organelles harbor the electron transport chain, bringing electrons in close vicinity to molecular oxygen. Although a full understanding is still lacking, intracellular ROS generation and mitochondrial function are also linked to changes in mitochondrial morphology. To study the intricate relationships between the different factors that govern cellular redox balance in living cells, we have developed a high-contentmicroscopy-based strategy for simultaneous quantification of intracellular ROS levels and mitochondrial morphofunction. Here, we summarize the principles of intracellular ROS generation and removal, and we explain the major considerations for performing quantitative microscopy analyses of ROS and mitochondrial morphofunction in living cells. Next, we describe our workflow, and finally, we illustrate that a multiparametric readout enables the unambiguous classification of chemically perturbed cells as well as laminopathy patient cells

An Evaluation of the COVID-19 Pandemic and Perceived Social Distancing Policies in Relation to Planning, Selecting, and Preparing Healthy Meals: An Observational Study in 38 Countries Worldwide

Objectives: To examine changes in planning, selecting, and preparing healthy foods in relation to personal factors (time, money, stress) and social distancing policies during the COVID-19 crisis. Methods: Using cross-sectional online surveys collected in 38 countries worldwide in April-June 2020 (N = 37,207, Mage 36.7 SD 14.8, 77% women), we compared changes in food literacy behaviors to changes in personal factors and social distancing policies, using hierarchical multiple regression analyses controlling for sociodemographic variables. Results: Increases in planning (4.7 SD 1.3, 4.9 SD 1.3), selecting (3.6 SD 1.7, 3.7 SD 1.7), and preparing (4.6 SD 1.2, 4.7 SD 1.3) healthy foods were found for women and men, and positively related to perceived time availability and stay-at-home policies. Psychological distress was a barrier for women, and an enabler for men. Financial stress was a barrier and enabler depending on various sociodemographic variables (all p < 0.01). Conclusion: Stay-at-home policies and feelings of having more time during COVID-19 seem to have improved food literacy. Stress and other social distancing policies relate to food literacy in more complex ways, highlighting the necessity of a health equity lens. Copyright 2021 De Backer, Teunissen, Cuykx, Decorte, Pabian, Gerritsen, Matthys, Al Sabbah, Van Royen and the Corona Cooking Survey Study Group.This research was funded by the Research Foundation Flanders (G047518N) and Flanders Innovation and Entrepreneurship (HBC.2018.0397). These funding sources had no role in the design of the study, the analysis and interpretation of the data or the writing of, nor the decision to publish the manuscript.Scopu

Transanal endoscopic microsurgery for rectal tumours using a Single Incision Laparoscopic Port.

Transanal endoscopic microsurgery (TEM), first described by Buess enables a less aggressive approach of benign rectal lesions, or even early rectal cancer in a curative intent. The SILS Port, initially designed for laparoscopic surgery, was successfully used for 20 TEM procedures in 16 patients. Local resection was sufficient in 15 procedures (benign tumours or pT1) out of 20, whereas 5 TEM operations required additional surgery: 3 rectal resections (pT1Nx, pT1sm3Nx and pT2N1) and 1 TEM revision (1 patient refused the rectal resection (pT1Nx). Postoperative complications following Dindo-Clavien were: grade II in 4 patients (pain: 2; fever: 1; bleeding: 1) and grade IIIb in 2 patients (bleeding). No long-term faecal incontinence was noted. TEM using the SILS Port is a safe and effective procedure for local resection of benign and certain malignant tumours. Using such a cheaper device, TEM procedure could be available in any operating theatre

Interleukin-6 production of uraemic haemodialysed patients: effects of different membranes.

Interleukin-6 (Il-6) has a complex spectrum of biological activities (growth and differentiation of B cells and synthesis of acute-phase proteins by liver). To evaluate the role of this cytokine in the inflammatory response induced by blood interaction with haemodialysis membranes, we have investigated Il-6 synthesis and release in supernatant of 24-h cultured peripheral blood mononuclear cells (PBMC) isolated from ten haemodialysed patients and eight healthy control subjects. In haemodialysed patients, blood samples were drawn before and after their usual dialytic treatment with cuprophane membranes and following 1 and 2 months with polymethylmethacrylate (PMMA) membranes. Il-6 was determined by 72-h incubation of serial dilutions of PBMC supernatant with Il-6-dependent cell line 7TD1; dilutions of rIl-6 were included as standard. Compared to Il-6 synthesis in control subjects (3.3 +/- 2.8 U/ml) the patients usually haemodialysed with cuprophane membranes showed significantly greater values (9.8 +/- 4.5 U/ml, P less than 0.02 before the treatment, and 10.4 +/- 6.1 U/ml, P less than 0.05 after the treatment). A significant reduction, in comparison with the values obtained with cuprophane membranes, was obtained after 1 month (5.3 +/- 2 U/ml, P less than 0.02 before the treatment, and 7.5 +/- 6 U/ml after the treatment) and especially after 2 months (3.4 +/- 3.2 U/ml, P less than 0.02 before the treatment, and 4.4 +/- 3.4 U/ml, P less than 0.05 after the treatment) of dialysis with PMMA membranes. In conclusion, our results show increased Il-6 production in haemodialysed patients usually treated with cuprophane membranes, suggesting a chronic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS