Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Predicting impacts of food competition, climate and disturbance on a long-distance migratory herbivore

Climate change is driving worldwide shifts in the distribution of biodiversity, and fundamental changes to global avian migrations. Some arctic‐nesting species may shorten their migration distance as warmer temperatures allow them to winter closer to their high‐latitude breeding grounds. However, such decisions are not without risks, since this intensifies pressure on resources when they are used for greater periods of time. In this study, we used an individual‐based model to predict how future changes in food abundance, winter ice coverage, and human disturbance could impact an Arctic/sub‐Arctic breeding goose species, black brant (Branta bernicla nigricans, Lawrence 1846), and their primary food source, common eelgrass (Zostera marina L.), at the Izembek Lagoon complex in southwest Alaska. Brant use the site during fall and spring migrations, and increasingly, for the duration of winter. The model was validated by comparing predictions to empirical observations of proportion of geese surviving, proportion of geese emigrating, mean duration of stay, mean rate of mass gain/loss, percentage of time spent feeding, number of bird days, peak population numbers, and distribution across the complex. The model predicted that reductions >50% of the current decadal (2007–2015) mean of eelgrass biomass, which have been observed in some years, or increases in the number of brant, could lead to a reduction in the proportion of birds that successfully migrate to their breeding grounds from the site. The model also predicted that access to eelgrass in lagoons other than Izembek was critical for overwinter survival and spring migration of brant, if overall eelgrass biomass was 50% of the decadal mean biomass. Geese were typically predicted to be more vulnerable to environmental change during winter and spring, when eelgrass biomass is lower, and thermoregulatory costs for the geese are higher than in fall. We discuss the consequences of these predictions for goose population trends in the face of natural and human drivers of change

Lipídeos na nutrição de cães e gatos: metabolismo, fontes e uso em dietas práticas e terapêuticas Lipids in dogs and cats nutrition: metabolism, sources and application in practical and therapeutic diets

A partir do desenvolvimento de métodos mais precisos para a avaliação de lipídeos, diversos compostos têm sido descobertos e estudados como forma de enriquecer e melhorar dietas para atender às necessidades dos animais. O triglicerídeo é o principal componente lipídico da dieta e fonte de ácidos graxos que são utilizados para a síntese de outros lipídicos importantes como os fosfolípideos. Os ácidos graxos dos fosfolipídeos possuem papel fundamental na sinalização celular e são substratos das enzimas específicas durante o processo de produção de mediadores de respostas imunológicas. Diversos estudos têm evidenciado a participação de grupos de ácidos graxos das séries ômega 3 e 6 influenciando as respostas inflamatórias em cães e gatos. A deficiência de ácido araquidônico em gatos, por exemplo, pode ser suprida pelo acréscimo de AA pré formado ou pela inclusão de ácido &#947;-linolênico na dieta, que mostrou-se eficiente na sustentação dos níveis de ácido araquidônico exigidos por gatos adultos. Há evidências de que ácidos graxos de cadeia média (AGCM) proporcionam maior incremento calórico durante o processo de oxidação celular, sugerindo sua funcionalidade sobre o controle da obesidade. Outros compostos lipídicos têm sido avaliados quanto a sua participação no processo de controle de ganho de peso. A ausência de um AA nos diacilgliceróis (DAG) pode ser na posição sn 2 ou sn 3 do glicerol gerando DAGs diferentes. O 1,3 DAG quando comparado ao TAG resulta em diferentes efeitos metabólicos que suportam a hipótese de que o acréscimo de DAG na dieta aumenta a oxidação hepática ou intestinal de lipídeos, limitando a deposição de ácidos graxos em triglicerídeos junto ao tecido adiposo.<br>Following the development of more accurate methods for lipid evaluation, various compounds have been discovered and studied as a way to improve and enrich diets to meet the animal requirements. Triglycerides are the major lipid component of diets and source of fatty acids that are used in the synthesis of important compounds as phospholipids. The fatty acids from phospholipids play a fundamental role in cell signaling and are substrates for specific enzymes in the synthesis of immune response mediators. Several studies have shown the involvement of fatty acids, omega 3 and 6 series as influencing the inflammatory responses in dogs and cats. The deficiency of arachidonic acid in cats, for example, can be supplied by preformed arachidonic acid or by addition of &#947;-linolenic acid in the diet, which in turn can sustain the arachidonic acid levels required by adult cats. Evidences suggest that medium chain fatty acids (MCFAs) trigger greater energy expenditure during cellular oxidation, thus indicating their use as an aid for weight control in obesity. Other lipid compounds are under evaluation in their possible effects in the weight gain process in dogs and cats. This absence of one FA in the DAG can be at the sn2 or sn3 position in glycerol, and thus generating different DAGs. The 1,3 DAG when compared to TAG results in different metabolic effects which support the hypothesis that the addition of DAG in diets increases the hepatic or intestinal oxidation of lipids, thus limiting the deposition of fatty acids in adipose tissue triglycerides

Testing a global standard for quantifying species recovery and assessing conservation impact.

Recognizing the imperative to evaluate species recovery and conservation impact, in 2012 the International Union for Conservation of Nature (IUCN) called for development of a "Green List of Species" (now the IUCN Green Status of Species). A draft Green Status framework for assessing species' progress toward recovery, published in 2018, proposed 2 separate but interlinked components: a standardized method (i.e., measurement against benchmarks of species' viability, functionality, and preimpact distribution) to determine current species recovery status (herein species recovery score) and application of that method to estimate past and potential future impacts of conservation based on 4 metrics (conservation legacy, conservation dependence, conservation gain, and recovery potential). We tested the framework with 181 species representing diverse taxa, life histories, biomes, and IUCN Red List categories (extinction risk). Based on the observed distribution of species' recovery scores, we propose the following species recovery categories: fully recovered, slightly depleted, moderately depleted, largely depleted, critically depleted, extinct in the wild, and indeterminate. Fifty-nine percent of tested species were considered largely or critically depleted. Although there was a negative relationship between extinction risk and species recovery score, variation was considerable. Some species in lower risk categories were assessed as farther from recovery than those at higher risk. This emphasizes that species recovery is conceptually different from extinction risk and reinforces the utility of the IUCN Green Status of Species to more fully understand species conservation status. Although extinction risk did not predict conservation legacy, conservation dependence, or conservation gain, it was positively correlated with recovery potential. Only 1.7% of tested species were categorized as zero across all 4 of these conservation impact metrics, indicating that conservation has, or will, play a role in improving or maintaining species status for the vast majority of these species. Based on our results, we devised an updated assessment framework that introduces the option of using a dynamic baseline to assess future impacts of conservation over the short term to avoid misleading results which were generated in a small number of cases, and redefines short term as 10 years to better align with conservation planning. These changes are reflected in the IUCN Green Status of Species Standard