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

Investigation of Resistance and Behavior of Reinforced Concrete Members Subjected to Dynamic Loading: Part III

Defense Atomic Support AgencyOffice of the Chief of Engineers, U.S. Army.Contract DA 49-129-Eng-34

Should we allow human-induced migration of the Indo-West Pacific fish, barramundi Lates calcarifer (Bloch) within Australia?

Some biologists have expressed concerns about the possible genetic impacts of translocation between stocks of barramundi Lates calcarifer (Bloch) in Australia. Recent genetic, biogeographical studies have provided an understanding of the evolution of the currently observed population structure in Australian barramundi by assessing the impacts of ice-age, sea-level changes on their distribution. These studies found that genetic differences between most barramundi populations are extremely small, have arisen in the past 17 000 years, and substantial migration and hybridization between eastern and western populations, isolated for at least 110 000 years, has occurred naturally. Some phenotypic support for these minor genetic differences can be inferred from the lack of adaptation to temperature in growth and survival responses of widely separated stocks (tropical and temperate). Based on a low level of genetic differentiation and high levels of gene flow between populations, with little evidence of local adaptation, translocation between populations should not pose a significant risk or problem

Mitochondrial DNA evidence for rapid colonisation of the Indo- West Pacific by the mudcrab Scylla serrata

Scylla serrata (Forskål, 1775) is widely distributed throughout mangrove habitats of the Indo-West Pacific (IWP) coastal waters. This study investigated the phylogeographic distribution of S. serrata mitochondrial DNA haplotypes sampled throughout the species range. Adults were sampled from three west Indian Ocean locations (N = 21), five west Pacific sites (N = 28) and three sites from northern and eastern Australia (N = 76). Temperature-gradient gel-electrophoresis and sequencing of 549 base pairs of a mtDNA gene (cytochrome oxidase 1) identified 18 distinct haplotypes. Haplotypes cluster into two clades separated by ≃2% sequence-divergence. One clade is widespread throughout the IWP, the other is strictly confined to northern Australia. Genealogical assessment of sequenced haplotypes suggests that the historical spread of S. serrata throughout the IWP has occurred rapidly and recently (<1 million years before present) from a west Pacific origin. The fact that many locations contain a single unique haplotype suggests limited contemporary gene flow between trans-oceanic sites, and that recent historical episodes of population founding and retraction have both determined and affected the current distribution of S. serrata populations. Contrary to that reported for other widespread species of IWP taxa, there is no pattern of regional separation of Indian from Pacific Ocean populations. However, results do suggest a vicariant separation of northern Australian crabs prior to the IWP radiation. We speculate that this separation may have resulted in the formation of a new species of Scylla

Genetic variation and stock structure of school mackerel and spotted mackerel in northern Australian waters

The total mean sample heterozygosity calculated from eight polymorphic loci was 0·172 (0·047 S.E.) (Fst 0·025) for school mackerel Scomberomorus queenslandicus, and for spotted mackerel S. munroi was 0·110 (0·074 S.E.) (Fst 0·038). There was no evidence of temporal variation for either species as significant genetic differences were not detected between months or year classes within areas. Spatially, school mackerel have a complex stock structure, with stocks being associated with large embayments. In contrast, spotted mackerel appear to comprise a single stock in Australian east coast waters. Both species showed a significant pattern of stock structure between Australian east coast and northern (Arafura Sea) samples

Influences of light intensity and photoperiod on moulting and growth of Penaeus merguiensis cultured under laboratory conditions

The effects of light intensity (I, 750 and 75 lx) and photoperiod (P, 12L/12D and 7L/5D) on moulting and growth of Penaeus merguiensis were investigated over 12 weeks under laboratory conditions. Both light intensity and photoperiod significantly (P0.05), prawns cultured at 750 lx tended to moult more frequently. Sexual dimorphism was not observed within the range of tested prawns