Small tails tell tall tales - intra-individual variation in the stable isotope values of fish fin

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Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Gut content and stable isotope analyses provide complementary understanding of ontogenetic dietary shifts and trophic relationships among fishes in a tropical river

1. Despite widespread recognition of the role of body size in fish trophic ecology, little attention has been focused on this issue in isotopic studies, particularly in tropical systems. \ud \ud 2. We used analyses of stomach contents and stable isotopes to examine size-related shifts in diet in a terapontid fish assemblage in the Australian wetdry tropics. Stomach content analysis identified substantial ontogenetic dietary shifts in all species, corresponding to changes in body sizeisotope trajectories for two species. Shifts away from relatively specialised diets of heavily ¹³C-depleted insect larvae to consumption of a range of items across multiple basal carbon sources appeared to be the proximate cause of observed isotopic changes. \ud \ud 3. Allochthonous organic matter in the form of C3 riparian vegetation was particularly important to smaller terapontids before larger fish shifted to a broad range of dietary items and similarly broad range of basal carbon sources. \ud \ud 4. While there was general agreement between δ¹³C and stomach content analysis, there was minimal concurrence between the latter and δ¹⁵N isotopic derivation of estimates of trophic position. Due to factors such as omnivory, isotopically overlapping basal sources and uncertainties about rates of isotopic fractionation in both predator and prey species, stomach content analysis provides an essential complement to isotopic methodologies in tropical systems. \ud \ud 5. Given that basal sources supporting any individual species can change markedly with ontogeny, consideration of intraspecific, size-related variation is necessary in isotopic studies of food web structure

Impacts of run-of-river hydropower on food web structure and mercury bioaccumulation in American dippers of coastal British Columbia

Run-of-river (RoR) dams are an increasingly common alternate energy source on mountain streams. Despite reductions in dam size and greenhouse gas emissions compared to conventional impoundments, RoR hydro may have ecotoxicological impacts through disruption of the natural flow regime. The American Dipper (Cinclus mexicanus) is a high trophic level river bird that occupies mountain streams suitable for RoR dams year-round and are known indicators of stream health; thus, they are an ideal species to study potential impacts of run-of-river hydropower. The objectives of this study are to 1) characterize the food web upstream and downstream of regulated and unregulated streams using stable isotopes (δ13C, δ15N, δ34S); 2) evaluate the methylmercury biomagnification potential upstream and downstream of regulated streams and compare dipper methylmercury levels between regulated and unregulated streams; and 3) determine if in-stream and riparian habitat features important for river birds are altered by run-of-river dams. Food webs were sampled at regulated and unregulated streams using a paired design a) upstream and downstream of 7 regulated and 7 unregulated streams and b) between regulated and unregulated streams. Surveys have found dippers congregating immediately upstream and downstream of several RoR dams in coastal BC, particularly during autumn. This has led to the hypothesis that reduced flow associated with these small dams creates a novel habitat in which dippers may forage more efficiently. Analyses of the blood and invertebrate samples from 14 streams has revealed isotopic changes on regulated streams, specifically 34S-depleted dipper blood, suggesting microbial activity associated with the headponds. We are assessing whether this modified habitat reflects higher levels of methylmercury than upstream of the dam or nearby unregulated streams. This study is an opportunity to examine the effects of reduced and stabilized flow on lotic food webs and improve our understanding of methylmercury biomagnification in mountain streams

Productivity and connectivity in tropical riverscapes of northern Australia: Ecological insights for management

Flow regimes are fundamental to sustaining ecological characteristics of rivers worldwide, including their associated floodplains. Recent advances in understanding tropical river–floodplain ecosystems suggest that a small set of basic ecological concepts underpins their biophysical characteristics, especially the high levels of productivity, biodiversity and natural resilience. The concepts relate to (1) river-specific flow patterns, (2) processes ‘fuelled’ by a complex of locally generated carbon and nutrients seasonally mixed with carbon and nutrients from floodplains and catchments, (3) seasonal movements of biota facilitated by flood regimes, (4) food webs and overall productivity sustained by hydrological connectivity, (5) fires in the wet/dry tropical floodplains and riparian zones being major consumers of carbon and a key factor in the subsequent redistribution of nutrients, and (6) river–floodplains having inherent resilience to natural variability but only limited resilience to artificial modifications. Understanding these concepts is particularly timely in anticipating the effects of impending development that may affect tropical river–floodplains at the global scale. Australia, a region encompassing some of the last relatively undisturbed tropical riverine landscapes in the world, provides a valuable case study for understanding the productivity, diversity and resilience of tropical river–floodplain systems. However, significant knowledge gaps remain. Despite substantial recent advances in understanding, present knowledge of these highly complex tropical rivers is insufficient to predict many ecological responses to either human-generated or climate-related changes. The major research challenges identified herein (for example, those related to food web structure, nutrient transfers, productivity, connectivity and resilience), if accomplished in the next decade, will offer substantial insights toward assessing and managing ecological changes associated with human alterations to rivers and their catchments

Longitudinal variation of isotope ratios in fin ray and fin membrane.

<p>Comparison of the (a) carbon (<i>δ</i>¹³C), (b) nitrogen (<i>δ</i>¹⁵N), (c) hydrogen (<i>δ</i>²H) and (d) oxygen (<i>δ</i>¹⁸O) stable ratios of tip and base sections of the ray and membrane components of non-treated Atlantic salmon fins. 1:1 lines are added to each plot for visualisation purposes.</p

Variation of isotope ratios in salmon fin (TMB).

<p>Comparison of the (a) carbon (<i>δ</i>¹³C), (b) nitrogen (<i>δ</i>¹⁵N), (c) hydrogen (<i>δ</i>²H) and (d) oxygen (<i>δ</i>¹⁸O) stable isotope ratios of base and tip sections of non-treated Atlantic salmon fins. 1:1 lines are added to each plot for visualisation purposes.</p

Variation of isotope ratios between fin ray and fin membrane.

<p>Comparison of the (a) carbon (<i>δ</i>¹³C), (b) nitrogen (<i>δ</i>¹⁵N), (c) hydrogen (<i>δ</i>²H) and (d) oxygen (<i>δ</i>¹⁸O) stable ratios of ray and membrane components of tip, mid and base sections of non-treated Atlantic salmon fins. 1:1 lines are added to each plot for visualisation purposes.</p