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

New sauropodomorph and cynodont remains from the Late Triassic Sacisaurus site in southern Brazil and its stratigraphic position in the Norian Caturrita Formation

Sacisaurus agudoensis is the only silesaurid known from the Triassic beds of the Santa Maria Supersequence and the correlation of its type locality to the other Triassic deposits of south Brazil has always been controversial. In an attempt to improve this, a handful of dinosaur and cynodont remains found associated to S. agudoensis are here described and compared. The anatomy of the sauropodomorph is more similar to that of Norian forms such as Pantydraco caducus and Unaysaurus tolentinoi than to that of Carnian taxa such as Saturnalia tupiniquim and Pampadromaeus barberenai. The cynodonts recovered based on isolated teeth include a brasilodontid and a Riograndia-like form. This assemblage is consistent with a Norian age, as is also suggested by local stratigraphic correlation, which positions the site in the Caturrita Formation

Chemical composition and energy value of guava and tomato wastes for broilers chickens at different ages Composição química e valores energéticos dos resíduos de goiaba e tomate para frangos corte em diferentes idades

The chemical composition and energy value of guava and tomato wastes for broilers at different ages were determined in this research. The metabolism assays were carried out by using the methodology of total excreta collection to calculate the chemical composition of wastes collected in different months. A total of 270 COBB broiler chicks was used: 150 in the period from 1 to 8 days of age (phase 1) and 120 chicks were used in the period from 10 to 17 days of age (phase 2). The trials were analyzed as completely randomized design with three treatments with five replications of 10 and 8 birds at the respective ages. The treatments consisted of different diets: one reference diet, one with 30% tomato meal and another with 20% guava meal, both partially replacing the reference diet. The values of the chemical composition of guava and tomato wastes varied according to the collection season. The chemical composition indicated that the wastes can be used in poultry feed, but with high crude fiber contents. The values of apparent metabolizable energy and nitrogen-corrected apparent metabolizable energy and of gross energy metabolizability coefficient of guava waste was not affected by the birds age, different from the result observed for tomato waste, whose digestibility coefficients and apparent metabolizable energy values varied among growing phases. The apparent metabolizable energy values (AME) for broilers form 1 to 8 and from 10 to 17 days of age were 1,331 and 1,358 kcal/kg for guava waste and from 2,351 to 2,465 kcal/kg for tomato waste.<br>Objetivou-se determinar a composição química e os valores nergéticos dos resíduos de goiaba e de tomate para frangos de corte em diferentes idades. Os resíduos foram coletados em meses distintos e, posteriormente, determinada a composição química por meio de ensaios de metabolismo utilizando a metodologia da coleta total de excretas. Utilizaram-se 270 pintos de corte da linhagem COBB, sendo 150 no período de 1 a 8 dias e 120 no período de 10 a 17 dias de idade. Nos ensaios utilizou-se o delineamento inteiramente casualizado e três tratamentos com cinco repetições de 10 e 8 aves nas respectivas idades. Os tratamentos consistiram de três dietas: uma dieta referência, uma com 30% de farelo de tomate e outra com 20% de farelo de goiaba, ambas substituindo parte da ração referência. Os valores de composição química dos resíduos da goiaba e do tomate variaram quanto à época de coleta. Os resíduos apresentaram composição satisfatória para alimentação de aves, porém com altos teores de fibra bruta. Os valores de energia metabolizável o coeficiente de metabolizabilidade da energia bruta do resíduo da goiaba não sofreram influência da idade das aves. Para o resíduo de tomate os valores de energia metabolizável aparente e coeficiente de metabolização variaram entre as idades. Os valores de energia metabolizável aparente corrigida para pintos de corte de 1 a 8 e de 10 a 17 dias de idade foram de 1.331 e 1.358 kcal/kg para o resíduo de goiaba e de 2.351 e 2.465 kcal/kg para o resíduo de tomate