Coupled 230Th/234U-ESR analyses for corals: A new method to assess sealevel change

Although coupled 230Th/234U-ESR analyses have become routine for dating teeth, they have never been used for corals. While the ESR age depends on, and requires assumptions about, the time-averaged cosmic dose rate, over(D, -)cos (t), 230Th/234U dates do not. Since over(D, -)cos (t) received by corals depends on the attenuation by any intervening material, over(D, -)cos (t) response reflects changing water depths and sediment cover. By coupling the two methods, one can determine the age and a unique over(D, -)cos, coupled (t) simultaneously. From a coral's water depth and sedimentary history as predicted by a given sealevel curve, one can predict over(D, -)cos, sealevel (t) . If over(D, -)cos, co

ESR analyses for teeth from the open-air site at Attirampakkam, India: Clues to complex U uptake and paleoenvironmental change

In open-air sites, diagenetic alteration makes teeth difficult to analyze with electron spin resonance (ESR). Despite strong diagenetic alteration, three ungulate teeth from Pleistocene fluvial sediment in the open-air Paleolithic site at Attirampakkam, Tamil Nadu, India, were analyzed using standard and isochron ESR. Diagenetic alteration features in two teeth indicated rapid submergence in quiet saline to hypersaline water, following a short subaerial exposure, while the third remained constantly buried under reducing conditions. Geochemical signatures and ESR data all indicate that the teeth experienced at least three independent U uptake events during diagenesis, including two that occurred long after burial

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

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization 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