50 research outputs found

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

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    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

    Toler\ue2ncia de Himatanthus sucuuba Wood. (Apocynaceae) ao alagamento na Amaz\uf4nia Central

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    Himatanthus sucuuba is a tree species with known phytotherapic value which colonizes both white-water floodplains (várzea) and upland forests (terra firme) in Central Amazonian. The objective of this study was to compare germination and initial seedling development from seeds collected in both the ecosystems. There was no significant difference between dry seed mass, but in a four month period in a glasshouse in Manaus, Brazil, germination rate differed according to the substrate and origin of the seeds. In the substrate sand + sawdust (non-flooded) germination rate was high, independent of seed origin (várzea 94% and terra firme 91%). In the substrate constituted only by water (flooded), the seeds originating from várzea had a higher germination rate (96%) and seedling formation (84%) than those originating from terra firme which had a germination rate of 64% and none of the seeds formed seedlings. In this treatment, the radicles rot few days after their emission, indicating that the seeds originating from várzea present adaptive characteristics to the floodplain environment which are not present in seeds from terra firme

    Testes de vigor na avaliação da qualidade fisiológica de sementes Erythrina velutina Willd. (FABACEAE - PAPILIONOIDEAE) Vigor tests in the evaluation of physiological quality of Erythrina velutina Willd. (FABACEAE- PAPILIONOIDEAE) seeds

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    A aplicação de testes de vigor de sementes tem sido fundamental para determinação da qualidade fisiológica de forma rápida e eficaz, destacando-se, os testes baseados no desempenho das plântulas como uma das opções disponíveis. Conduziu-se este trabalho, com o objetivo de avaliar a eficiência de testes de vigor para determinação da qualidade fisiológica de sementes de Erythrina velutina. Determinou-se em cinco lotes de sementes de E. velutina o teor de água e o peso de mil sementes e realizou-se os testes de germinação, emergência em campo, índice de velocidade de germinação e de emergência, comprimento e massa seca de plântulas do laboratório e campo. Os testes de campo (emergência de plântulas, índice de velocidade de emergência de plântulas e massa seca da parte aérea das plântulas) são eficientes na separação dos lotes de sementes de E. velutina em níveis de vigor.<br>The application of vigor tests of seeds has been fundamental as a fast and efficient form of determination of physiological seed quality, highlighting the tests based on the performance of seedlings as one of the available options. The objective of this study was to evaluate the efficiency of different vigor tests for the determination of the physiologic quality of Erythrina velutina seeds. In five lots of E. velutina seeds, water content and seed weight were determined. Tests for germination were performed for field seedling emergence, speed germination and emergence index, and length and dry matter weight of seedlings from both the laboratory and from the field. Field tests (seedling emergence, speed emergence index, and dry matter weight of the aerial part of seedlings) are efficient in the separation of the seed lots of E. velutina in vigor levels
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