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

Rule-based inspection of printed green ceramic tape

A template-based vision system for the 100% inspection of printed flaws on green ceramic tape has been developed. Design goals included a requirement for the detection of flaws as small as two thousandths of an inch on parts up to 8 by 8 inches in size. The inspection engine is a Datacube, Inc., MV200 pipeline processor. As each part is inspected, four 2K by 2K pixel quadrant images are stitched together to construct a single 4K by 4K pixel image with the aid of multiple fiducials located in each quadrant. The part fiducial locations, mask image, and punched-hole position data are generated, beforehand, from CAD designs using a defect map editor (DME), a preprocessing software package developed for the PC. The DME also generates a part ``defect map``. Each unique structure in the printed pattern is defined as an object. Objects are grouped into user-defined categories such as die pads, contact fingers, traces, and electrolysis buses. The map is used during the runtime inspection to associate each detected defect with an object group and a particular defect specification for that group. Repeat defects are optionally tracked for up to three consecutive parts

Characterization of biological types of cattle: indicator traits offertility in beef cows

Genetic diversity among breeds of cattle allows producers to select animals for specific environments or market conditions. Reproductive efficiency is a multi-component trait that is largely influenced by environmental influences such as health and nutritional status; however, there are clearly genetic components to reproductive efficiency, and breed differences in a number of indicator traits associated with fertility and cow productivity have been identified. Historical indicators of fertility include scrotal circumference, age at puberty, and postpartum interval. Both age at puberty and postpartum interval are laborious traits to collect in heifers and cows because they require many days of detection of behavioral estrus. In recent years, the addition of ultrasonography to management practices has allowed for the collection of female traits such as follicle diameter, antral follicle counts, and fetal age that are not as labor intensive. These additional diagnostic traits provide novel phenotypes for the identification of genetic markers of fertility and cow productivity, which would be the ultimate goal. Genetic markers of the number of follicles in the bovine ovary have the potential to identify heifers that will be highly productive cows. Furthermore, identifying and understanding the genes that control various reproductive traits and the response to stressors, such as temperature and nutrient availability, could improve production efficiency by improving management and breeding decisions in a wide range of production environments

Efeitos do manejo pós-parto de vacas primíparas no desempenho de bezerros de corte até um ano de idade Effects of post-partum management of primiparous cows on growth of beef calves up to one year of age

Os efeitos no desenvolvimento de bezerros submetidos a: a) três tratamentos, consitindo de cargas animais pós-parto (CA) de 240 kg de peso vivo (PV)/ha (tratamento 1, T1), de 320 kg de PV/ha (T2), ambas em campo nativo, e de 400 kg de PV/ha em pastagem melhorada de azevém (Lolium multiflorum L.) por 80 dias pós-parto e, posteriormente, em CA igual à do T2 em campo nativo (T3); b) duas idades de desmame, consistindo de desmame aos 100 (DP) ou 180 (DC) dias de idade, foram avaliados utilizando 92 bezerros filhos de vacas primíparas Hereford e Braford. O sexo dos bezerros influenciou significativamente o peso ao nascer, não sendo observado efeito da raça da vaca. Os tratamentos e a raça da vaca não influenciaram o ganho médio diário (GMD) dos bezerros do nascimento ao desmame precoce. Bezerros filhos de vacas Braford tiveram maiores pesos no DP (PDP) que os filhos de vacas Hereford, enquanto os tratamentos não influenciaram o PDP. Os bezerros filhos de vacas Braford no T2 tiveram GMD até os 180 dias (GMD180) e PV aos 180 dias (PAJ180) superiores aos bezerros filhos de vacas Braford no T1 e Hereford no T2. Os bezerros do DP tiveram GMD180 e PAJ180 significativamente inferiores aos bezerros do DC. Entretanto, não se verificaram efeitos de tratamentos e idade de desmame sobre o GMD até os 365 dias e o peso ajustado aos 365 dias de idade. Portanto, os três manejos pós-parto das vacas e as duas idades de desmame dos bezerros avaliados não influenciaram o desenvolvimento dos bezerros a um ano de idade.<br>The effects on the performance of calves submitted to: a) three treatments, consisted of post-partum stocking rates (CA) of 240 kg of live weight (LW)/ha (treatment 1, T1), of 320 kg of LW/ha (T2), both on natural pastures, and of 400 kg of LW/ha on improved pasture of Italian ryegrass (Lolium multiflorum L.) during the first 80 days post-partum, and after on natural pasture at the same stocking rate as T2 afterwards (T3); b) two weaning ages, consisted of weaning at 100 (EW) and at 180 (CW) days of age, were evaluated using 92 beef calves from Hereford and Braford primiparous cows. The sex of the calves affected significantly the birth weight, and no effect was observed for the breed of cow. The treatments and breed of cow did not affect the average daily gain (ADG) of the calves from birth to early weaning (GEW). Calves born from Braford cows had higher LW at EW (WEW) than calves born from Hereford cows, while the WEW was not affected by the treatments. Calves born from Braford cows on T2 had ADG up to 180 days (ADG180) and LW at 180 days (LW180) greater than calves born from Braford cows on T1 and Hereford cows on T2. Calves from CW had greater LW180 and ADG180 than calves from EW. However, treatments and weaning ages did not affect the LW at 365 days and the ADG up to 365 days of age. The three cows post-partum management schemes and the two calves weaning ages evaluated did not affect the calves performance up to one year of age