Amphid sensory neurons of Caenorhabditis elegans orchestrate its survival from infection with broad classes of pathogens

The survival of a host during infection relies on its ability to rapidly sense the invading pathogen and mount an appropriate response. The bacterivorous nematode Caenorhabditis elegans lacks most of the traditional pattern recognition mechanisms. In this study, we hypothesized that the 12 pairs of amphid sensory neurons in the heads of worms provide sensing capability and thus affect survival during infection. We tested animals lacking amphid neurons to three major classes of pathogens, namely—a Gram-negative bacterium Pseudomonas aeruginosa, a Gram-positive bacterium Enterococcus faecalis, and a pathogenic yeast Cryptococcus neoformans. By using individual neuronal ablation lines or mutants lacking specific neurons, we demonstrate that some neurons broadly suppress the survival of the host and colonization of all pathogens, whereas other amphid neurons differentially regulate host survival during infection. We also show that the roles of some of these neurons are pathogen-specific, as seen with the AWB odor sensory neurons that promote survival only during infections with P. aeruginosa. Overall, our study reveals broad and specific roles for amphid neurons during infections.</p

Homeostatic control of stearoyl desaturase expression via patched-like receptor PTR-23 ensures the survival of C. elegans during heat stress

Organismal responses to temperature fluctuations include an evolutionarily conserved cytosolic chaperone machinery as well as adaptive alterations in lipid constituents of cellular membranes. Using C. elegans as a model system, we asked whether adaptable lipid homeostasis is required for survival during physiologically relevant heat stress. By systematic analyses of lipid composition in worms during and before heat stress, we found that unsaturated fatty acids are reduced in heat-stressed animals. This is accompanied by the transcriptional downregulation of fatty acid desaturase enzymes encoded by fat-1, fat-3, fat-4, fat-5, fat-6, and fat-7 genes. Conversely, overexpression of the Δ9 desaturase FAT-7, responsible for the synthesis of PUFA precursor oleic acid, and supplementation of oleic acid causes accelerated death of worms during heat stress. Interestingly, heat stress causes permeability defects in the worm’s cuticle. We show that fat-7 expression is reduced in the permeability defective collagen (PDC) mutant, dpy-10, known to have enhanced heat stress resistance (HSR). Further, we show that the HSR of dpy-10 animals is dependent on the upregulation of PTR-23, a patched-like receptor in the epidermis, and that PTR-23 downregulates the expression of fat-7. Consequently, abrogation of ptr-23 in wild type animals affects its survival during heat stress. This study provides evidence for the negative regulation of fatty acid desaturase expression in the soma of C. elegans via the non-canonical role of a patched receptor signaling component. Taken together, this constitutes a skin-gut axis for the regulation of lipid desaturation to promote the survival of worms during heat stress.<br/

Nations within a nation: variations in epidemiological transition across the states of India, 1990–2016 in the Global Burden of Disease Study

18% of the world's population lives in India, and many states of India have populations similar to those of large countries. Action to effectively improve population health in India requires availability of reliable and comprehensive state-level estimates of disease burden and risk factors over time. Such comprehensive estimates have not been available so far for all major diseases and risk factors. Thus, we aimed to estimate the disease burden and risk factors in every state of India as part of the Global Burden of Disease (GBD) Study 2016

G protein-coupled receptors: The choreographers of innate immunity in Caenorhabditis elegans.

Caenorhabditis elegans is a free-living, bacterivorous nematode that frequently encounterspathogens while foraging for food in decomposing vegetation. Like other invertebrates, C. elegans entirely relies on its innate immune system to combat invading pathogens. A basal flightor fight response of animals is also observed in worms against infection. The former is an aversion response of C. elegans against select pathogens, and the latter is an inducible innateresponse comprising of pathogen-specific effectors including lysozymes, lectins, antimicrobialpeptides (AMPs), and cytoprotective molecules. Although pathogen recognition in worms ispoorly understood, various signaling pathways and immune effectors facilitating defenseresponse are well studied, making this nematode an excellent model to study host–microbeinteractions. In higher vertebrates such as mice and humans, sensing of infection throughpathogen-associated molecular patterns (PAMPs) or host damage-associated molecular patterns (DAMPs) is primarily mediated by the toll-like receptors (TLRs), nod-like receptors(NLRs), RIG-I like receptors (RLRs), C-type lectin domain (CTLD) proteins, and AIM-likereceptors (ALRs) [1]. Humans have 10 TLRs that sense PAMPs and DAMPs. However, TOL1, the only TLR homolog in C. elegans, does not seem to be essential during infections withmost pathogens, except during Salmonella enterica [2] and Serratia marcescens [3] infections.The C. elegans RIG-I like receptor DRH-1 detects products of viral replication and activates anintracellular pathogen response [4]. CLEC-39 and CLEC-49, two CTLD proteins in C. elegans,are essential for immune responses against S. marcescens and are known to bind live bacteria[5]. Despite all these findings, the molecular mechanisms involved in pattern recognition by C.elegans during a majority of infections remain elusive. In this review, we examine the roles ofG protein-coupled receptors (GPCRs) as noncanonical pattern recognition receptors (PRRs)and also discuss how GPCR signaling in C. elegans regulates various immune processes.GPCRs form the largest superfamily of cell surface receptors in eukaryotes; C. elegansencodes approximately 1,300 genes encoding putative GPCRs [6]. They are involved in a variety of physiological processes [7] and also for detecting various environmental cues, includingbacterial secondary metabolites [8]. In recent years, several studies on infection in C. eleganshave revealed the importance of GPCRs and their signaling in host defense. In this review, weexamine the role of GPCRs in innate immunity via the modulation of “flight” or “fight”responses of C. elegans

Magnetic resonance elastography for staging liver fibrosis in non-alcoholic fatty liver disease: a diagnostic accuracy systematic review and individual participant data pooled analysis

OBJECTIVES: We conducted an individual participant data (IPD) pooled analysis on the diagnostic accuracy of magnetic resonance elastography (MRE) to detect fibrosis stage in patients with NAFLD. METHODS: Through a systematic literature search, we identified studies of MRE (at 60–62.5Hz) for staging fibrosis in patients with NAFLD, using liver biopsy as gold standard and contacted study authors for IPD. Through pooled analysis, we calculated the cluster-adjusted AUROC, sensitivity and specificity of MRE for any (≥stage 1), significant (≥stage 2) and advanced fibrosis (≥stage 3) and cirrhosis (stage 4). RESULTS: We included 9 studies reporting on 232 patients with NAFLD (mean age, 51±13y; 37.5% males; mean BMI, 33.5±6.7 kg/m(2); interval between MRE and biopsy <1 year, 98.3%). Fibrosis stage distribution (stage 0/1/2/3/4) was 33.6%, 32.3%, 10.8%, 12.9% and 10.4%, respectively. Mean AUROC (and 95% confidence intervals) for diagnosis of any (≥stage 1), significant (≥stage 2) or advanced fibrosis (≥stage 3) and cirrhosis was 0.86 (0.82–0.90), 0.87 (0.82–0.93), 0.90 (0.84–0.94) and 0.91 (0.76–0.95), respectively. Similar diagnostic performance was observed in stratified analysis based on sex, obesity, and degree of inflammation. CONCLUSIONS: Based on pooled IPD analysis, MRE has high diagnostic accuracy for detection of fibrosis in NAFLD, independent of BMI and degree of inflammation