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

Flowers and fruits in Flacourtiaceae. I. Scaphocalyx spathacea Ridl

Descriptions are given of the flowers, fruits, and seeds. The petals have basal scales. The pistil is an urceolate structure issuing in 5—7 stigmas. In it are two whorls of ovules along the wall, the lower whorl in the same radial planes as are the stigmas, the upper whorl in alternate radii. The pistil wall is entirely covered by nectariferous hairs. There is a peculiar vascular bundle pattern. The ovule is sessile and atropous, the nucellus is beaked, the inner integument terminates into 2—4 projections, the outer integument into 2—4 lobes. The ovules develop into inferior seeds mainly by proximal growth. Lobes of the endocarp grow around the ectostome. The testa has its hard layer in the middle. The seeds consist of two parts, a hard container containing a free kernel, an air mantle being enclosed. This is probably a swimming device. As, moreover, the fruit is pulpous, the species probably is diplochorous. The results are put against the theory of metamorphosis and the carpel theory. It is thought that this Malaysian plant is a very unusual, possibly ancient, monotype

Flowers and fruits in Flacourtiaceae. II. The seeds of Pangium edule Reinw

The seeds are inferior. Only in the apical part of the seed the testa is integumental; for the greater part it is chalazal. A thick mesotesta is formed by a matted layer of sclereids. The chalazal part of the ectotesta is richly vascularized. A sheath of inverted vascular bundles occurs on the inside of the chalazal part of the mesotesta. The seeds are albuminous, the cotyledons foliaceous. An inside cavity may make the seeds float in water. The nucellar beak persists in the ripe seed. The endopyle is five-rayed in c.s., the ectopyle is a longitudinal slit

On the development of some Gynoecia with septal nectaries

Septal nectaries are formed by local regions of later nectariferous epidermal cells on the sides of the carpels at their very base. In order that the epidermal cells may differentiate into nectariferous cells, the carpels which constitute the gynoecium have to develop as separate organs. It was argued that if no septal nectaries develop, this free carpel development does not take place. The nectariferous regions get shaped as nectar containers by dermal fusion of the sides of the carpels surrounding them, by upward growth of the apex, and mostly also by meristematic continuity of part of the ovary wall on the outside. By the latter the level of the openings of the nectaries on the ovary is defined. Septal nectaries in Monocotyledons are considered original

The early development of inflorescences and flowers of the oil palm (Elaeis guineensis Jacq.) seen through the scanning electron microscope

The development of inflorescences and flowers of the African Oil Palm up to anthesis is illustrated by scanning electron microscopy images. The time of origin relative to the development of the foliage leaves of the basipetalous succession of flowering rachillae is determined, as well as the time of morphological sex definition. The logical stage when sex is determined is inferred to be not before the first appearance of the spikelet primordia. Female flower groups develop acropetally as triaxial cincinni, the male units as reduced ones. A developmental diagram is added

Note on the floral development of Thottea (Aristolochiaceae)

The occurrence of four placentae is a constant character in Thottea. The species can be distinguished by differences in the androecium. The androecial pattern is relatively variable and its rather high plasticity in the genus is suggested to be a derived feature within the family. The gynoecial structure is most remarkable, as the stylar organs do not correspond with the placentae in number nor in position. It is assumed that these organs do not belong to the gynoecium morphologically. They may represent independent, phylogenetically secondary organs, which may function in the capturing of pollen

Reviews

This study is a full-sounding prelude to the fundamental work on the morphology of inflorescences, which is being prepared by Prof. Dr. W. Troll of Mainz. All inflorescences in Valerianaceae are understood as modifications of one basic form, the thyrse. It is gratifying to note that forms of inflorescences, described in systematical works as for instance 1) capitate or interruptedly spicate (Plectritis), 2) compound dichasium, dichotomous throughout (cymoid Valeriana spp.), or dichotomously branched inflorescence (Valerianella), 3) ‘rispig bis fast trugdoldig’ (Phuodendron), in reality all are variations on one theme, the decussate mono-, to pleiothyrse, i. e. a simple to compound inflorescence with a racemous primary axis and cymous lateral axes. The transformations take place first of all by a favoured development of lateral axes on definite heights of the main axis (‘basi-mesotoner, akrotoner Förderungssinn’) and secondly by the number of flowers developing and the more or less pronounced tendency to form monochasia. Moreover, different forms such as loose panicles, umbels, glomerules, heads and even nearly simple racemes (Aretiastrum), originate by extension or reduction of axes of some or all orders