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

Alterações morfológicas e alocação de biomassa em plantas jovens de espécies florestais sob diferentes condições de sombreamento Morphologic alterations and biomass allocation in young plants of forestry species under different conditions of shading

A seleção de espécies nativas e/ou exóticas para recuperação de ambientes degradados ou alterados pode ser baseada no potencial de aclimatação das espécies a diferentes níveis de luminosidade. Nesse contexto, o objetivo deste estudo foi avaliar o efeito do sombreamento (0%, 30% e 50% de interceptação da radiação solar incidente) no crescimento, na alocação de biomassa e nos teores de clorofila total de plantas jovens de quatro espécies florestais de diferentes grupos ecológicos: Maclura tinctoria (L.) D. Don ex Steud. (moreira), Senna macranthera (Collad.) Irwin et Barn. (fedegoso), Hymenaea courbaril L. var. stilbocarpa (Hayne) Lee et Lang. (jatobá) e Acacia mangium Willd. (acácia). Os maiores teores de clorofila total foram observados em condições sombreadas, para todas as espécies. A espécie clímax exigente em luz (moreira), apresentou os maiores resultados de crescimento. Em condições de pleno sol, a espécie pioneira (acácia) alocou mais biomassa em folhas enquanto que a espécie clímax exigente em luz (moreira) produziu mais raízes. Estas observações evidenciam o potencial de aclimatação a diferentes condições de disponibilidade de irradiação, que deve ser considerado em programas de recuperação de ambientes degradados e manejo de áreas naturais.<br>The selection of native and/or exotic species for recovery of degraded or perturbed environment can be associated with the acclimatation potential of species in different conditions of shading. In this context, the objective of this research was to evaluate the effect of shading (0%, 30% and 50% of interception of the incident solar radiation) on growth, biomass allocation and chlorophyll levels in young plants of forestry species from different ecological groups: Maclura tinctoria (L.) D. Don ex Steud. (moreira), Senna macranthera (Collad.) Irwin et Barn. (fedegoso), Hymenaea courbaril L. var. stilbocarpa (Hayne) Lee et Lang. (jatobá) e Acacia mangium Willd. (acácia). The results obtained showed that the higher chlorophyll levels were observed in shaded conditions for all species. The climax lighting demanding specie (moreira) showed the highest growth. In sunny conditions, the pioneer species (acacia) produced more leaves while the climax light demanding species (moreira) produced more roots. These observations indicated that these species are capable of acclimation to different conditions of radiation availability, a result that should be considered in regeneration programs of degraded environment and management of natural areas

Crescimento inicial de plantas de Cryptocaria aschersoniana Mez. submetidas a níveis de radiação solar Early growth of plants of Cryptocaria aschersoniana Mez. submitted to radiation solar levels

O plantio de essências nativas, seja com finalidade econômica ou conservacionista, requer uma série de cuidados que dependem do conhecimento prévio de suas características fisiológicas e exigências ecológicas nas diversas etapas de seu ciclo vital. O estudo do crescimento e desenvolvimento de uma planta, em diferentes condições ambientais, oferece ao pesquisador bom indício sobre quais as melhores condições para se cultivar determinada espécie. Objetivou-se avaliar o crescimento inicial e as concentrações de clorofilas em plantas jovens de Cryptocaria aschersoniana Mez. (Canela-Batalha), submetidas a níveis de redução da radiação solar: 0% (Pleno Sol), 30%, 50% e 70%. Os resultados demonstram que o teor de clorofila total foi maior nas plantas cultivadas em 70% de sombreamento, o mesmo ocorrendo com a razão clorofila a/b. A maior altura foi apresentada pelas plantas cultivadas em 50% de sombreamento. Do ponto de vista de acúmulo de matéria seca total e matéria seca de raízes, a melhor performance foi observada nas plantas em 30% de sombreamento e o maior acúmulo de matéria seca de folhas verificado nas plantas cultivadas em 30 e 50% de sombreamento. Conclui-se que as melhores condições de cultivo para mudas de Cryptocaria aschersoniana Mez. (Canela-Batalha) foram os níveis de 30 e 50% de redução da radiação solar incidente.<br>The cultivation of native essences with economical or conservacionist purpose needs a serie of cares that need some previous knowledgment of the physiological and ecologic characteristics of the diverses phases of the life cycle. The study of the growth and development of a plant under different environmental conditions offers to the researcher a good clue on which the best conditions to grow a particular species. It was aimed at to evaluate the initial growth and the concentration of chlorophylls in young plants of Cryptocaria aschersoniana Mez. (Canela-Batalha) submitted to levels of reduction of solar radiation: 0% (full sunlight), or 30, or 50 or 70%. The results demonstrate that the concentration of total chlorophyll was larger in the plants grown under 70% of shading, the same happened with the ratio of chlorophyll a/b. The greatest plant height was observed in the plants grown in 50% of shading. From the standpoint of total biomass accumulated and root dry matter, the best performance was observed in the plants under 30% of shading and the higher leaves dry matter accumulation was verified in the plants grown under 30 and 50% shading. It is ended that the best ones growing conditions for seedlings of Cryptocaria aschersoniana Mez. (Canela-Batalha) were the levels of 30 and 50% of reduction of the incident solar radiation

ADMINISTRAÇÃO EPIDURAL DE OPIÓIDES EM CÃES EPIDURAL OPIOIDS ADMINISTRATION IN DOGS

Os opióides têm sido utilizados em Medicina Veterinária há vários anos como alternativa para o alívio da dor pós-operatória ou traumática. Atualmente, tem-se dado maior valor ao controle da dor nos animais, visando a oferecer melhores condições de recuperação ao paciente traumatizado ou recém-operado. A morfina foi o primeiro opióide usado em animais. Mais recentemente, a administração dessa substância, por via epidural, vem sendo empregada no controle da dor com resultados promissores. Assim, nesta revisão, abordam-se vários aspectos referentes aos efeitos e às indicações da administração epidural de opióides em cães.<br>Opioids have been used for several years to relieve traumatic pain in Veterinary Medicine. The painful stimulus are implicated with delayed tissue recuperation of surgical wounds. Today, a great importance has been given to pre-emptive control of post operative pain in animals. Indeed, the use of epidural morphine, the first opioid substance used in animals, has provided excellent analgesia and good condition at the immediate post operative period. In addition, several aspects concerning the effects indications and forms of epidural opioids injections in dogs are considered in this review

Crescimento de Hymenaea courbaril L. var. stilbocarpa (Hayne) Lee et Lang. e Enterolobium contortisiliquum (Vell.) Morong (Leguminosae) sob diferentes níveis de sombreamento Growth of Hymenaea courbaril L. var. stilbocarpa (Hayne) Lee et Lang. e Enterolobium contortisiliquum (Vell.) Morong (Leguminosae) under different shading levels

Hymenaea courbaril L. var. stilbocarpa (Hayne) Lee et Lang. é uma espécie clímax tolerante a sombra, ao passo que Enterolobium contortisiliquum (Vell.) Morong. é uma espécie pioneira. O desenvolvimento destas espécies pode refletir a habilidade de adaptação aos diferentes fatores ambientais (luz, água e temperatura) no local em que estão crescendo. O suprimento inadequado de um desses fatores pode reduzir o vigor da planta e limitar seu desenvolvimento. O presente trabalho teve como objetivo avaliar os efeitos do nível de sombreamento no crescimento e a concentração de pigmentos fotossintéticos em duas espécies de leguminosas arbóreas, Hymenaea courbaril L. var. stilbocarpa (Hayne) Lee et Lang. e Enterolobium contortisiliquum (Vell.) Morong. O experimento foi conduzido no Setor de Olericultura do Centro Universitário Luterano de Ji-Paraná (CEULJI/ULBRA)/Rondônia. Durante a formação das mudas, ambas as espécies foram expostas a quatro tratamentos de sombra: 0 % (controle - sol pleno); 30 %; 50 % e 80 %. Cada tratamento foi constituído com três repetições de cada espécie; o delineamento experimental foi inteiramente casualisado. Quatro meses após a semeadura, as seguintes análises foram realizadas: número de folhas, altura da planta, comprimento do sistema radicular, massa seca total e concentração de pigmentos fotossintéticos. O tratamento sob sol pleno afetou negativamente o crescimento de ambas as espécies. As mudas crescidas sob 50% e 80% apresentaram melhor desenvolvimento. Conforme o aumento do sombreamento houve um decréscimo na razão clorofila a/b e um aumento nas concentrações de clorofila total e carotenóides totais.<br>Hymenaea courbaril L. var. stilbocarpa (Hayne) Lee et Lang. is a clímax shadow tolerant specie and Enterolobium contortisiliquum (Vell.) Morong., by the other hand, is considered as a pioneer specie. The development of these species may reflect its adaptation ability to different environmental elements (light, water and temperature) at its growth site. An inadequate supply of some of these elements may reduce plant vigor and limit its development. This work aimed to evaluate the effects of shade intensity on the growth and photosynthetic pigment concentration of two arboreal legumes that are typical to northern Brazil, namely, the Hymenaea courbaril L. var. stilbocarpa (Hayne) Lee et Lang. and the Enterolobium contortisiliquum (Vell.) Morong. The experiment was carried out at the Centro Universitário Luterano de Ji-Paraná (CEULJ/ULBRA)/Rondônia. During the formation of the seedlings, both species were exposed to four treatments of shade: 0 % (control - without shade); 30 %; 50 % e 80 %. Each treatment was carried out with three replications for each species; the experimental design was completely randomized. Four month after sowing, the following analyses were carried out: number of leaves, plant height, roots length, dry mass and photosynthetic pigment concentration. The treatment under 0% shade impaired the seedling growth of both species. The most favorable treatments were 50 % and 80 % shade. According to the shade intensity, the chlorophyll a/b ratio decreased and the chlorophyll and carotenoids increased

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