Local proliferation dominates lesional macrophage accumulation in atherosclerosis

During the inflammatory response that drives atherogenesis, macrophages accumulate progressively in the expanding arterial wall1,2. The observation that circulating monocytes give rise to lesional macrophages3–9 has reinforced the concept that monocyte infiltration dictates macrophage build-up. Recent work indicates, however, that macrophages do not depend on monocytes in some inflammatory contexts10. We therefore revisited the mechanism of macrophage accumulation in atherosclerosis. We show that murine atherosclerotic lesions experience a surprisingly rapid, 4-week, cell turnover. Replenishment of macrophages in these experimental atheromata depends predominantly on local macrophage proliferation rather than monocyte influx. The microenvironment orchestrates macrophage proliferation via the involvement of scavenger receptor (SR)-A. Our study reveals macrophage proliferation as a key event in atherosclerosis and identifies macrophage self-renewal as a therapeutic target for cardiovascular disease

National identity predicts public health support during a global pandemic

Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = −0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.publishedVersio

Current advances in the inhibition of the auto-regulatory interaction between the p53 tumour suppressor protein and MDM2 protein

The p53 tumour suppressor protein is involved in co-ordinating the cellular response to genotoxic stress through initiating a G1-growth arrest and/or induction of apoptosis and thereby influences the success of most anticancer treatments. p53 is a damage-inducible transcription factor whose activity is negatively regulated by the binding of MDM2 protein. The ability to disrupt the p53-MDM2 regulatory loop has identified a novel therapeutic opportunity. Potent peptide inhibitors of the interaction between p53 and MDM2 protein have been identified, with IC50 values in the nanomolar range, and activate the p53-dependent stress response. Potentially, such peptides might have a wider application as non-genotoxic therapeutic p53 activators, in tumours that retain expression of wild type p53 protein, to induce the p53-dependent apoptotic pathway

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Not AvailableHeavy mortality in cage farmed cobia in the southeast coast of Tamil Nadu occurred during the summer of 2016 was investigated. About 60 per cent of the fish died following a few days of high temperature and low wind in the coastal region. The fish had an average size of 27.5 cm length and 200 g weight. The affected fish had focal erythematous lesions on the ventral distended abdomen, peritoneal serosanguinous fluid accumulation, splenomegaly and swollen kidney. Bacteriological examination of the peritoneal fluid, kidney and spleen revealed the presence of Gram negative short rods in large numbers. The bacteria grew as green colonies on thiosulphate citrate bile salt sucrose agar. The tissues were also screened for the presence of nervous necrosis nodavirus by PCR and cell culture but did not yield positive result. The bacterial strains isolated from the tissues were identified as Photobacterium damselae sub sp. damselae using API 20 E microbial identification kit. The species was confirmed by multiplex PCR for 16S rRNA and urease gene. Sequence analysis of 16S rRNA showed 99 per cent homogeneity with P. damselae subsp. damselae. One of the isolates was used for the pathogenicity study in sea bass fingerlings. The experimental infection was done by intraperitoneal administration of 50 micro liters of two dilutions of the culture at 4.2 ×10 raised to the power 5 and 4.2×103 cfu per fish. The experiment revealed that the bacteria were highly pathogenic to seabass and could induce 100 per cent mortality in 36 h. The same bacteria were re-isolated from kidney sample of moribund fish and were confirmed as Pdd with API test kits and 16S rRNA sequencing. The isolates were also screened for the presence of virulence genes.Not Availabl

Identification of DNA Components Required for Induction of Cotton Leaf Curl Disease

AbstractCotton leaf curl disease (CLCuD) is a major constraint to cotton production in Pakistan. Infectious clones of the monopartite begomovirus cotton leaf curl virus (CLCuV), associated with diseased cotton, are unable to induce typical symptoms in host plants. We have identified and isolated a single-stranded DNA molecule approximately 1350 nucleotides in length which, when coinoculated with the begomovirus to cotton, induces symptoms typical of CLCuD, including vein swelling, vein darkening, leaf curling, and enations. This molecule (termed DNA β) requires the begomovirus for replication and encapsidation. The CLCuV/DNA 1/DNA β complex, together with a similar complex previously identified in Ageratum conyzoides, represent members of an entirely new type of infectious, disease-causing agents. The implications of this finding to our understanding of the evolution of new disease-causing agents are discussed

Radiation-Induced Fibrosis: Mechanisms and Opportunities to Mitigate. Report of an NCI Workshop,

A workshop entitled "Radiation-Induced Fibrosis: Mechanisms and Opportunities to Mitigate" (held in Rockville, MD, September 19, 2016) was organized by the Radiation Research Program and Radiation Oncology Branch of the Center for Cancer Research (CCR) of the National Cancer Institute (NCI), to identify critical research areas and directions that will advance the understanding of radiation-induced fibrosis (RIF) and accelerate the development of strategies to mitigate or treat it. Experts in radiation biology, radiation oncology and related fields met to identify and prioritize the key areas for future research and clinical translation. The consensus was that several known and newly identified targets can prevent or mitigate RIF in pre-clinical models. Further, basic and translational research and focused clinical trials are needed to identify optimal agents and strategies for therapeutic use. It was felt that optimally designed preclinical models are needed to better study biomarkers that predict for development of RIF, as well as to understand when effective therapies need to be initiated in relationship to manifestation of injury. Integrating appropriate endpoints and defining efficacy in clinical trials testing treatment of RIF were felt to be critical to demonstrating efficacy. The objective of this meeting report is to (a) highlight the significance of RIF in a global context, (b) summarize recent advances in our understanding of mechanisms of RIF, (c) discuss opportunities for pharmacological mitigation, intervention and modulation of specific molecular pathways, (d) consider the design of optimal clinical trials for mitigation and treatment and (e) outline key regulatory nonprescriptive frameworks for approval