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

Sequence Control of the Self-Assembly of Elastin-Like Polypeptides into Hydrogels with Bespoke Viscoelastic and Structural Properties

The biofabrication of structural proteins with controllable properties via amino acid sequence design is interesting for biomedicine and biotechnology, yet a complete framework that connects amino acid sequence to material properties is unavailable, despite great progress to establish design rules for synthesizing peptides and proteins with specific conformations (e.g., unfolded, helical, β-sheets, or β-turns) and intermolecular interactions (e.g., amphipathic peptides or hydrophobic domains). Molecular dynamics (MD) simulations can help in developing such a framework, but the lack of a standardized way of interpreting the outcome of these simulations hinders their predictive value for the design of de novo structural proteins. To address this, we developed a model that unambiguously classifies a library of de novo elastin-like polypeptides (ELPs) with varying numbers and locations of hydrophobic/hydrophilic and physical/chemical-cross-linking blocks according to their thermoresponsiveness at physiological temperature. Our approach does not require long simulation times or advanced sampling methods. Instead, we apply (un)supervised data analysis methods to a data set of molecular properties from relatively short MD simulations (150 ns). We also experimentally investigate hydrogels of those ELPs from the library predicted to be thermoresponsive, revealing several handles to tune their mechanical and structural properties: chain hydrophilicity/hydrophobicity or block distribution control the viscoelasticity and thermoresponsiveness, whereas ELP concentration defines the network permeability. Our findings provide an avenue to accelerate the design of de novo ELPs with bespoke phase behavior and material properties. BN/Gijsje Koenderink La

Effects of sodium chloride on tobacco plants

The effect of salinity on the growth and ion concentrations in a number of tobacco cultivars is described. Sodium chloride, at a concentration of 200 mol m−3, hardly affected the fresh weight, but significantly reduced the dry weight. The difference in the response of fresh and dry weights to salt was due to a change in succulence (water per unit leaf area); the latter increased with increasing leaf Na+ and Cl− concentration. Under saline conditions, increasing the external Na+: Ca− ratio by decreasing the Ca2+ concentration increased the accumulation of Na+ and Cl− into the leaf tissue

Amorphe Mischhalbleiter auf der Basis von Silizium fuer Tandemsolarzellen Schlussbericht

SIGLETIB Hannover: FR 2241(Schl) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Duennschichtsolarzellen auf der Basis von amorphem Silizium Schlussbericht

The conversion efficiency, and predominantly the stability with respect to light-induced degradation of amorphous silicon (a-Si:H) based solar cells can considerably be improved by the use of a tandem or triple junction structure. The variation of the optical band-gap of a-Si:H can easily be accomplished by the additional incorporation of germanium or carbon into the amporphous network. However, the density of defect states of such alloys, both at mid-gap and in the band-tails, is strongly enhanced, and thus their optoelectronic properties correspondingly deteriorate with respect to pure a-Si:H. a-Si:H, a-Ge:H and amorphous alloy semiconductors (a-SiGe:H, a-SiC:H) with band-gaps of 1.1...2.1 eV were deposited by various methods, and optimized for the application in pin solar cells. Beyond these accomplishments, pin solar cells were fabricated on a laboratory scale, interface phenomena which substantially influence the device performance were investigated, a description of metastability on thermodynamic grounds was given, and a novel macroscopic grooving of the substrate was tested within first attempts to enhance the stabilized conversion efficiency of amorphous solar cellsDer Wirkungsgrad und vor allem die Stabilitaet gegenueber lichtinduzierter Degradation von Solarzellen auf der Basis amorphen Siliziums (a-Si:H) laesst sich mit Mehrbarrierensystemen, die Absorber mit abgestuften Bandabstaenden verwenden, erheblich verbessern. Die Variation des optischen Bandabstandes von a-Si:H gelingt sehr einfach durch zusAetzlich Einbau von Germanium oder Kohlenstoff, allerdings weisen solche Legierungen erhoehte Zustandsdichten in der Mitte der Quasibandluecke sowie den Bandauslaeufern auf und zeigen entsprechend schlechtere optoelektronische Eigenschaften als amorphes Silizium selbst. a-Si:H, a-Ge:H und amorphe Mischhalbleiter (a-SiGe:H, a-SiC:H) mit Bandabstaenden von (1,1-2,1) eV wurden mit verschiedenen Verfahren hergestellt und fuer die Anwendung in pin-Solarzellen optimiert. Darueber hinaus wurden pin-Solarzellen hergestellt, Grenzflaechenphaenomene untersucht, die deren Wirkungsgrad massgeblich beeinflussen, eine thermodynamisch begruendete Beschreibung der Metastabilitaet der untersuchten Halbleiter gegeben und eine neuartige makroskopische Strukturierung zur Erhhung der stabilisierten Wirkungsgrade amorpher Solarzellen erprobtSIGLEAvailable from TIB Hannover: F94B1214+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

Salinity resistance in Zea mays: fluxes of potassium, sodium and chloride, cytoplasmic concentrations and microsomal membrane lipids

Cytoplasmic concentrations, fluxes of K+, Na+ and Cl and microsomal membrane lipids were investigated in a salt-sensitive and salt-resistant variety of Zea mays. The salt resistance of Protador relative to LGH (salt-sensitive) appears to be related to higher K+ fluxes and cytoplasmic concentrations, and lower Na+ and Cl fluxes and cytoplasmic concentrations, when grown in NaCl. There were no apparent differences in the simple chemical composition of root microsomal membrane lipids between the two varicties, neither were these affected by salt

Acesso aos serviços de saúde: uma abordagem de geografia em saúde pública Access to health services: a geographical approach to public health

O acesso da população aos serviços de saúde é um pré-requisito de fundamental importância para uma eficiente assistência à saúde. A localização geográfica dos serviços é um dos fatores que interferem nessa acessibilidade. Pretendeu-se estudar a localização dos serviços de saúde. A proposta básica foi a de apresentação de uma metodologia considerando-se as relações de variáveis geográficas, demográficas e sociais. Enfatizou-se, no processo, a participação da comunidade. Efetuou-se o estudo da adequação dessa metodologia às características da região de Santo Amaro, Município de São Paulo, Brasil. A contribuição dada pela abordagem geográfica abre ampla perspectiva quanto ao estabelecimento de novas linhas de estudo, planejamento e gestão, advindas do intercâmbio entre a Geografia Humana e a Saúde Pública, numa área que se sugere denominar Geografia em Saúde Pública.<br>The access of the population to the health services is a requirement of basic importance for the efficiency of health assistance. The geographical localization of the services is one of the factors that interfere with this accessibility. It is intended to make a contribution to the study of the localization of health services. The basic proposal introduces a method which takes into account the relationships between geographical, demographical and social variables. Emphasis is placed on community participation in the process. The study of the adequacy of this method was undertaken under the regional characteristics of Santo Amaro, a suburb of the city of S. Paulo, Brazil. The contribution furnished by the geographical approach in this work opens up a broad perspective for the setting up of new lines of research, planning and administration resulting from the interation between human geography and public health within the common field for which it is suggested Geography of Public Health

Interacción genotipo-ambiente en avena sativa l: utilizando los modelos AMMI y factorial de correspondencias Genotype-environment interaction in avena sativa l: employing AMMI and factorial correspondence models

El objetivo fue (i) determinar la presencia de interacción genotipo-ambiente (IGA) en la producción forrajera de avena (Avena sativa L.) de genotipos tolerantes y no tolerantes a Schizaphis graminum empleando un número bajo de ambientes en la provincia de Buenos Aires (Argentina) mediante los modelos de efectos principales aditivos e interacción multiplicativa (AMMI) y análisis factorial de correspondencias (AFC) y (ii) comparar los resultados obtenidos por ambos métodos. Los ensayos se condujeron en La Dulce (Argentina) y La Plata (Argentina) (1993, 1994 y 1995). Se evaluaron 12 genotipos (comerciales y líneas avanzadas) en 12 ambientes (combinación de localidad, años y cortes). Los factores ambiente, genotipo e interacción explicaron un 41,15% (p<0,001), 7,88% (p<0,05) y 36,36% (p<0,001) de la suma de cuadrados del total respectivamente. El modelo AMMI mostró los tres primeros ejes del análisis de componentes principales (ACP) altamente significativos (p<0,001), explicando un 57,99%, 29,03% y 6,27% de la suma de cuadrados de la interacción respectivamente. Las tres primeros ejes del AFC explicaron un 58,98%, 29,58% y 5,60% de dicha suma de cuadrados, respectivamente. El uso conjunto de ambos métodos surge como una herramienta muy útil para reflejar y caracterizar la existencia de interacción genotipo-ambiente en avena.<br>The objective of this study was (i) to determine the presence of genotype-environment interaction (GXE) in Avena sativa l. for above dry matter yield of Schizaphis graminun tolerant and non-tolerant genotypes according to two different models: additive main effects and multiplicative interaction (AMMI) and factorial correspondence analysis; and (ii) to study and compare the results obtained with these models. Twelve genotypes and 12 environments were conducted at La Dulce and La Plata (Argentina) during three years (1993, 1994 and 1995). The environment (E), genotype (G) and GxE factors explained a 41.15%, 7.88% and 36.36% of the total sum of square, respectively. The first three axes of principal component analysis of AMMI were highly significant (p<0.001), explaining a 57.99%, 29.03% and 6.27% of interaction sum of square. The first three factorial correspondence coordinates accounted for 58.98%, 29.58% and 5.60% of the interaction sum of square. The relationships between tolerant genotypes-first clipping environments and non-tolerant genotypes-second clipping environments were reflected in the biplots of both models. The simultaneous use of AMMI and factorial correspondence analysis appeared as a useful methodology for the study of GxE interaction in the oat breeding for tolerance to Schizaphis graminum