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

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Not AvailableCastor (Ricinus communis L.) is one of the oldest cultivated crops, but currently it represents only 0.15% of the vegetable oil produced in the world. Castor oil is of continuing importance to the global specialty chemical industry because it is the only commercial source of a hydroxylated fatty acid. Castor also has tremendous future potential as an industrial oilseed crop because of its high seed oil content (more than 480 g kg–1), unique fatty acid composition (900 g kg–1 of ricinoleic acid), potentially high oil yields (1250–2500 L ha–1), and ability to be grown under drought and saline conditions. Th e scientifi c literature on castor has been generated by a relatively small global community of researchers over the past century. Much of this work was published in dozens of languages in journals that are not easily accessible to the scientifi c community. Th is review was conducted to provide a compilation of the most relevant historic research information and defi ne the tremendous future potential of castor. Th e article was prepared by a group of 22 scientists from 16 institutions and eight countries. Topics discussed in this review include: (i) germplasm, genetics, breeding, biotic stresses, genome sequencing, and biotechnology; (ii) agronomic production practices, diseases, and abiotic stresses; (iii) management and reduction of toxins for the use of castor meal as both an animal feed and an organic fertilizer; (iv) future industrial uses of castor including renewable fuels; (v) world production, consumption, and prices; and (vi) potential and challenges for increased castor productionNot Availabl

Gradiente florístico das florestas secundárias do Nordeste Paraense Floristic gradient of the northeast Paraense secondary forests

O presente estudo descreve um gradiente florístico de uma cronosequência de florestas secundárias do Nordeste Paraense, a partir de 19 sítios de diferentes idades, avaliados em diferentes anos. Foram usados os dados de densidade e realizada análise de regressão para riqueza, diversidade, densidade, densidade relativa máxima e equibilidade em relação à idade. Foi usado o método de análise de agrupamento hierárquico, sendo a distância euclidiana utilizada como medida de dissimilaridade e aplicada uma Análise de Componente Principal (PCA) para confirmação dos grupos. Após a definição dos grupos, foi feita a análise indicadora de espécies (IndVal) sobre a mesma matriz utilizada para análise de agrupamento. Encontrou-se um gradiente geográfico na cronosequência analisada e as espécies Tapirira guianensis, Vismia guianensis, Inga alba, Lacistema aggregatum, Croton maturensis, Abarema jupunba, Inga rubiginosa, Guateria poepigiana e Thyrsodium paraense, são indicadoras das florestas secundárias do Nordeste Paraense analisadas neste estudo.<br>This study describes a floristic gradient of secondary forest chronosequence in northeast of Pará State - Brazil, from 19 sites of different ages, evaluated in different years. We used density data and carried out regression analysis for richness, diversity, density, maximum relative density and equitability in relation to the age. We used the hierarchic grouping method of analysis and the Euclidean distance as dissimilarity measure, and applied a Principal Component Analysis (PCA) for confirming the groups. After defining the groups, we made an indicating species analysis (IndVal) on the same matrix used for the grouping analysis. We found a geographic gradient in the chronosequence analyzed and the species Tapirira guianensis, Vismia guianensis, Inga alba, Lacistema aggregatum, Croton maturensis, Abarema jupunba, Inga rubiginosa, Guateria poepigiana and Thyrsodium paraense to be indicators of the northeast Para (Brazil) secondary forests analyzed in this study