cGAS-STING effectively restricts murine norovirus infection but antagonizes the antiviral action of N-terminus of RIG-I in mouse macrophages

Although cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling has been well recognized in defending DNA viruses, the role of cGAS-STING signaling in regulating infection of RNA viruses remains largely elusive. Noroviruses, as single-stranded RNA viruses, are the main causative agents of acute viral gastroenteritis worldwide. This study comprehensively investigated the role of cGAS-STING in response to murine norovirus (MNV) infection. We found that STING agonists potently inhibited MNV replication in mouse macrophages partially requiring the JAK/STAT pathway that induced transcription of interferon (IFN)-stimulated genes (ISGs). Loss- and gain-function assays revealed that both cGAS and STING were necessary for host defense against MNV propagation. Knocking out cGAS or STING in mouse macrophages led to defects in induction of antiviral ISGs upon MNV infection. Overexpression of cGAS and STING moderately increased ISG transcription but potently inhibited MNV replication in human HEK293T cells ectopically expressing the viral receptor CD300lf. This inhibitory effect was not affected by JAK inhibitor treatment or expression of different MNV viral proteins. Interestingly, STING but not cGAS interacted with mouse RIG-I, and attenuated its N-terminus-mediated anti-MNV effects. Our results implicate an essential role for mouse cGAS and STING in regulating innate immune response and defending MNV infection. This further strengthens the evidence of cGAS-STING signaling in response to RNA virus infection

Search for long-lived, massive particles in events with displaced vertices and multiple jets in pp collisions at √s = 13 TeV with the ATLAS detector

A search for long-lived particles decaying into hadrons is presented. The analysis uses 139 fb−1 of pp collision data collected at √s = 13 TeV by the ATLAS detector at the LHC using events that contain multiple energetic jets and a displaced vertex. The search employs dedicated reconstruction techniques that significantly increase the sensitivity to long-lived particles decaying in the ATLAS inner detector. Background estimates for Standard Model processes and instrumental effects are extracted from data. The observed event yields are compatible with those expected from background processes. The results are used to set limits at 95% confidence level on model-independent cross sections for processes beyond the Standard Model, and on scenarios with pair-production of supersymmetric particles with long-lived electroweakinos that decay via a small R-parity-violating coupling. The pair-production of electroweakinos with masses below 1.5 TeV is excluded for mean proper lifetimes in the range from 0.03 ns to 1 ns. When produced in the decay of m(g∼) = 2.4 TeV gluinos, electroweakinos with m(χ∼01) = 1.5 TeV are excluded with lifetimes in the range of 0.02 ns to 4 ns

Application of predictive model for vaginal birth after caesarean delivery

Medical practitioners are concerned with the selection of delivery mode after caesarean delivery. Several researchers have developed numerous models for predicting vaginal birth after caesarean delivery. This study selected seven widely used and representative advanced models, such as those of Grobman, Troyer and Parisi, Schoorel, Flamm, Gonen, Weinstain and Smith et al., analysed the constitutions and clinical applications of the models and identified the factors associated with patients to provide midwives a scientific reference for vaginal delivery evaluation of pregnant women after caesarean delivery. Keywords: Predictive model, Vaginal birth after caesarean deliver

Acacetin—A simple flavone exhibiting diverse pharmacological activities

Acacetin (5,7-dihydroxy-4-methoxyflavone) is a naturally occurring flavonoid, known to possess numerous pharmacological properties, including neuroprotective, cardioprotective, anticancer, anti-inflammatory, antidiabetic, and antimicrobial activities. The molecule is widespread throughout the Plant Kingdom, but is particularly abundant in the Asteraceae, Euphorbiaceae, Passifloraceae, Lamiaceae and Malvaceae families. It has been shown to exhibit strong inhibitory effects against glutathione reductase, cyclo-oxygenase, acetylcholinesterase, aldose reductase and xanthine oxidase enzymes. A comprehensive overview of the potential therapeutic applications of acacetin was prepared after collating selected peer-reviewed papers, accessed from online scientific databases, specifically PubMed, Web of Science and Scopus. The mechanism of action, dose forms and structure-activity relationships of the molecule are some of the aspects discussed in the review, to facilitate further research and use of this molecule

Zebrafish Neurobehavioral Phenomics for Aquatic Neuropharmacology and Toxicology Research

Zebrafish (Danio rerio) are rapidly emerging as an important model organism for aquatic neuropharmacology and toxicology research. The behavioral/phenotypic complexity of zebrafish allows for thorough dissection of complex human brain disorders and drug-evoked pathological states. As numerous zebrafish models become available with a wide spectrum of behavioral, genetic, and environmental methods to test novel drugs, here we discuss recent zebrafish phenomics methods to facilitate drug discovery, particularly in the field of biological psychiatry. Additionally, behavioral, neurological, and endocrine endpoints are becoming increasingly well-characterized in zebrafish, making them an inexpensive, robust and effective model for toxicology research and pharmacological screening. We also discuss zebrafish behavioral phenotypes, experimental considerations, pharmacological candidates and relevance of zebrafish neurophenomics to other \u27omics\u27 (e.g., genomic, proteomic) approaches. Finally, we critically evaluate the limitations of utilizing this model organism, and outline future strategies of research in the field of zebrafish phenomics. (C) 2015 Elsevier B.V. All rights reserved