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

A visual assessment of vegetation structure for the Kruger National Park

Vegetation structure was assessed visually for 1045 of the 1093 quadrats (2.5' x 2.5', ca 4 x 4 km) that cover the Kruger National Park. Vegetation categories recorded were-woody vegetation (broad-leaved, mopane, fine-leaved, mixed, riparian, treeless, scrub bushes and trees); ground cover (grass, grassless and open areas); and emergent large trees (baobab, live and dead). The results are available as grid maps or as files on the Internet. The categories were selected for their relevance to bird distribution but can be applied to other organisms

Transcriptomic Analysis of Laser Capture Microdissected Tumors Reveals Cancer- and Stromal-Specific Molecular Subtypes of Pancreatic Ductal Adenocarcinoma

International audienceAbstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) lethality is multifactorial; although studies have identified transcriptional and genetic subsets of tumors with different prognostic significance, there is limited understanding of features associated with the minority of patients who have durable remission after surgical resection. In this study, we performed laser capture microdissection (LCM) of PDAC samples to define their cancer- and stroma-specific molecular subtypes and identify a prognostic gene expression signature for short-term and long-term survival. Experimental Design: LCM and RNA sequencing (RNA-seq) analysis of cancer and adjacent stroma of 19 treatment-naïve PDAC tumors was performed. Gene expression signatures were tested for their robustness in a large independent validation set. An RNA-ISH assay with pooled probes for genes associated with disease-free survival (DFS) was developed to probe 111 PDAC tumor samples. Results: Gene expression profiling identified four subtypes of cancer cells (C1–C4) and three subtypes of cancer-adjacent stroma (S1–S3). These stroma-specific subtypes were associated with DFS (P = 5.55E-07), with S1 associated with better prognoses when paired with C1 and C2. Thirteen genes were found to be predominantly expressed in cancer cells and corresponded with DFS in a validation using existing RNA-seq datasets. A second validation on an independent cohort of patients using RNA-ISH probes to six of these prognostic genes demonstrated significant association with overall survival (median 17 vs. 25 months; P < 0.02). Conclusions: Our results identified specific signatures from the epithelial and the stroma components of PDAC, which add clarity to the nature of PDAC molecular subtypes and may help predict survival

Screening for Corynebacterium diphtheriae and Corynebacterium ulcerans in patients with upper respiratory tract infections 2007-2008: a multicentre European study

AbstractDiphtheria is now rare in most European countries but, when cases do arise, the case fatality rate is high (5–10%). Because few countries continue to routinely screen for the causative organisms of diphtheria, the extent to which they are circulating amongst different European populations is largely unknown. During 2007–2008, ten European countries each screened between 968 and 8551 throat swabs from patients with upper respiratory tract infections. Six toxigenic strains of Corynebacterium diphtheriae were identified: two from symptomatic patients in Latvia (the country with the highest reported incidence of diphtheria in the European Union) and four from Lithuania (two cases, two carriers); the last reported case of diphtheria in Lithuania was in 2002. Carriage rates of non-toxigenic organisms ranged from 0 (Bulgaria, Finland, Greece, Ireland, Italy) to 4.0 per 1000 (95% CI 2.0–7.1) in Turkey. A total of 28 non-toxigenic strains were identified during the study (26 C. diphtheriae, one Corynebacterium ulcerans, one Corynebacterium pseudotuberculosis). The non-toxigenic C. ulcerans strain was isolated from the UK, the country with the highest reported incidence of cases due to C. ulcerans. Of the eleven ribotypes detected, Cluj was seen most frequently in the non-toxigenic isolates and, amongst toxigenic isolates, the major epidemic clone, Sankt-Petersburg, is still in circulation. Isolation of toxigenic C. diphtheriae and non-toxigenic C. diphtheriae and C. ulcerans in highly-vaccinated populations highlights the need to maintain microbiological surveillance, laboratory expertise and an awareness of these organisms amongst public health specialists, microbiologists and clinicians

Neoplastic–Stromal Cell Cross-talk Regulates Matrisome Expression in Pancreatic Cancer

International audienc

Conserving large carnivores : dollars and fence

Conservationists often advocate for landscape approaches to wildlife management while others argue for physical separation between protected species and human communities, but direct empirical comparisons of these alternatives are scarce. We relate African lion population densities and population trends to contrasting management practices across 42 sites in 11 countries. Lion populations in fenced reserves are significantly closer to their estimated carrying capacities than unfenced populations. Whereas fenced reserves can maintain lions at 80% of their potential densities on annual management budgets of $500 km−2, unfenced populations require budgets in excess of$2000 km−2 to attain half their potential densities. Lions in fenced reserves are primarily limited by density dependence, but lions in unfenced reserves are highly sensitive to human population densities in surrounding communities, and unfenced populations are frequently subjected to density-independent factors. Nearly half the unfenced lion populations may decline to near extinction over the next 20–40 years.Research funded by Adrian Gardiner/Mantis Collection (AL), African Wildlife Foundation (SB,LF), Wendy Arnold (LF), Arthur Blank Family Foundation (LF), Australian Research Council - DP0987528 (KZ), Australian Research Council – LP0990395 (SG), Banovich Wildscapes Foundation (LF), Bateleurs (RS), Boesak Kruger Fund (LF,AL), Born Free (SB,SC), Michael Calvin (LF), Charles Darwin University (STG,KKZ), Cheryl Grunbock & Martin King Foundation (LF), Chicago Board of Trade for Endangered Species (RG), Columbus Zoo (SB,TC,RG,LF), Conservation Force (LF,PF), Dallas Ecological Foundation (LF), Dallas Safari Club (LF), Darwin Initiative for Biodiversity (AL), Paul Davies (SMD), Denver Zoo (LF), Directors of Ongava Game Reserve (KJS), Disney Worldwide Conservation Fund (CMB,KSB,CP,RS), Dominion Oil (EOO, AP), Earthwatch Institute #5123 (SMK,BP), Fairplay Foundation (CMB,KSB), Fauna & Flora International (CMB,KSB), Flora Family Foundation (LF), Frankenberg Foundation (AL), Stephen Gold (LF), Green Trust WWF-SA (RS), GTZ/Pendjari Project (EAS), Hluhluwe Tourism Assoc. (RS), Houston Zoo (CMB,KSB,JWMcN), Idea Wild (HBr), Kenya Wildlife Service (SK), Lakeside Foundation (SMD), Lee & Juliet Folger Foundation (JWMcN), Lillian Jean Kaplan Foundation (AL), Lion Ore (KN), Bruce Ludwig (LF), Malilangwe Trust (BC), Mara Conservancy (BH), MGM Grand Hotel (CP,RS), Mohamed Bin Zayed Species Fund (HHdeI), N. & R. Myhrvold (JWMcN), National Geographic Big Cat Initiative (HHdeI,JWMcN), National Geographic Society (SB,HBr,TC,LF,RG,CP), National Research Foundation (RS), Netherlands Committee for IUCN (HHdeI), Netherlands Support Program for the Garoua Wildlife School (HBa), NSF (LF,JS), NSF DEB-0 613 730(DMacN), NSF DEB-1 020 479(CP), Okavango Wildlife Society (KN), Ol Pejeta Ranch Ltd. (NG,CN), Panthera (GB,CMB,KSB,HBr,LF, LH,BK, PL,AL,CP,EOO,AP,EAS), Panthera Kaplan Awards Program (ACB,LF), PG Allen Family Foundation (JWMcN), Philadelphia Zoological Society (LF,KN,KS), Porini Camp Amboseli (LF), Potrero Nuevo Fund (LF), Predator Conservation Trust (CMB,KSB), Rann Safaris (CW,HW), Rufford Foundation (CMB,KSB,LF,KN), Rufford-Maurice-Laing Foundation (AL), Kathy Ruttenberg (AP), Safari South (C&HW), San Francisco Zoo (LF), SCI Foundation (LF), Seaworld/Busch Gardens Conservation Foundation (SB,LF), Technology and Human Resources for Industry Programme, SA (RS), Thandiza Foundation and the Rotterdam Zoo (KN), Tshwane University of Technology – Faculty Research Committee (PF), Tshwane University of Technology – Postgraduate Scholarship Programme (SMM), Tusk Trust (JWMcN), University of KwaZulu-Natal (RS), US Forest Service (AP), US National Cancer Institute (LF), Van Tienhoven Foundation (HBa), Jonathan Vannini (LF), Vectronic Aerospace (LF), West Midlands Safari Park (KS), Debby Wettlaufer (LF), Wild about Cats (RS), Wild Entrust International (JWMcN), Wildlife Conservation Network (CMB,KSB,LF), Wildlife Conservation Society (CMB,KSB,LF,BK,EOO,AP), Wildlife Conservation Trust KZN (RS), Wildlife Direct (LF), Wildlife Division of the Forestry Commission of Ghana (ACB), Woodland Park Zoo (JWMcN) and World Wide Fund for Nature (HHdeI).http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1461-0248hb201

Spatial patterns of large African cats: a large-scale study on density, home range size, and home range overlap of lions Panthera leo and leopards Panthera pardus

Environmental Biolog