13 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

    Determinants of local abundance in a major radiation of Australian passerines (Aves: Meliphagoidea)

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    Aim&ensp; To identify the factors that contribute to variation in abundance (population density), and to investigate whether habitat breadth and diet breadth predict macroecological patterns in a suborder of passerine birds (Meliphagoidea).Location&ensp; Australia (including Tasmania).Methods&ensp; Mean abundance data were collated from site surveys of bird abundance (the Australian Bird Count); range size and latitudinal position data from published distribution maps; and body mass and diet breadth information from published accounts. A diversity index of habitats used (habitat breadth) was calculated from the bird census data. We used bivariate correlation and multiple regression techniques, employing two phylogenetic comparative methods: phylogenetic generalized least squares and independent contrasts.Results&ensp; Body mass and latitude were the only strong predictors of abundance, with larger-bodied and lower-latitude species existing at lower densities. Together, however, body mass and latitude explained only 11.1% of the variation in mean abundance. Range size and habitat breadth were positively correlated, as were diet breadth and body mass. However, neither range size, nor habitat breadth and diet breadth, explained patterns in abundance either directly or indirectly.Main conclusions&ensp; Levels of abundance (population density) in meliphagoid birds are most closely linked to body mass and latitudinal position, but not range size. As with many other macroecological analyses, we find little evidence for aspects of niche breadth having an effect on patterns of abundance. We hypothesize that evolutionary age may also have a determining effect on why species tend to be rarer (less abundant) in the tropics.<br /

    Proximate body composition of the larval, metamorphosing and downstream migrant stages in the life cycle of the Southern Hemisphere lamprey, Geotria australis

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    The water, total lipid, protein and ash content have been measured in larval, metamorphosing (stages 1-7) and downstream migrant Geotria australis caught in Western Australia between October 1977 and August 1979. The total lipid content of ammocoetes changed markedly with season and increased with body size. Although, unlike other species, the ammocoetes of G. australis continue to increase in length during the latter part of larval life, the relative amount of total lipid still rose during this period, eventually reaching levels equivalent to approximately 14% of the wet body weight at the commencement of metamorphosis. During the six months between the onset of metamorphosis and the downstream migration, total lipid declined to approximately 8%. Assays for phospholipid of larval and metamorphosing G. australis indicated that changes in total lipid were almost entirely due to variations in neutral lipid. Changes in the percentage amount of total lipid were accompanied by an inverse but slightly greater amount of change in percentage water. During metamorphosis, the absolute amount of total lipid in a 'standard animal' declined from 122 mg at stage 1 to 53 mg at stage 7, whereas water rose initially from 597 mg at stage 1 to 638 mg at stage 3, before declining to 442 mg by stage 7. Although the percentage amount of protein and ash tended to increase slightly during larval life, neither showed conspicuous seasonal changes. In both relative and absolute terms, protein declined during metamorphosis. A comparison of the data on the proximate body composition in G. australis and holarctic lampreys shows that different strategies have been employed to accumulate large amounts of fat by the end of larval life and to utilize protein during metamorphosis

    Anatomia e ultra-estrutura foliar de Cyperus maritimus Poir. (Cyperaceae): estratégias adaptativas ao ambiente de dunas litorâneas Leaf anatomy and ultrastructure of Cyperus maritimus Poir. (Cyperaceae): adaptive strategies for coastal dune environment

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    Foram analisados aspectos anatômicos e ultra-estruturais foliares de Cyperus maritimus Poir. visando identificar caracteres adaptativos ao ambiente de dunas litorâneas. Para isto, indivíduos ocorrentes nas dunas da Praia de Pipa, Rio Grande do Norte, Brasil, tiveram as folhas submetidas a diferentes análises: microscopia de luz, eletrônica de varredura e de transmissão. Em vista frontal, a epiderme possui tricomas unicelulares, corpos de sílica, cutícula estriada e depósitos de cera. Em secção transversal, a epiderme é unisseriada com parede periclinal externa espessa. Os estômatos são paracíticos, podendo o ostíolo estar obstruído por cera. Abaixo da face adaxial observa-se o parênquima aqüífero. Os feixes vasculares ocorrem em múltiplas fileiras, sendo as periféricas compostas por feixes de diâmetro menor que os feixes da fileira central. Foram observados caracteres relacionados à síndrome Kranz do tipo clorociperóide. Aspectos ultra-estruturais, como cloroplastos presentes na bainha do feixe, esses sem grana evidentes, entre outras características, reforçam a possível ocorrência da via C4 nesta espécie. É a primeira citação para o gênero Cyperus de cloroplasto nas celulas do tecido vascular. Neste trabalho foi possível observar vários caracteres importantes para plantas submetidas a estresse hídrico e salino, como: cera, células epidérmicas com parede periclinal externa espessada, parênquima aqüífero e síndrome Kranz.<br>Anatomical and ultrastructural aspects of Cyperus maritimus Poir. were analyzed with the aim of identifying adaptive features for the dune environment. Collections were made at Pipa beach, Rio Grande do Norte, Brazil. Leaves were submitted to different analyses: light microscopy, scanning and transmission electron microscopy. In frontal view, the epidermis has unicellular trichomes, silica bodies, a striate cuticle and wax deposits. In transverse section, the epidermis is uniseriate with thickened outer periclinal walls. The stomata are paracitic and the pore sometimes obstructed by wax. Under the adaxial epidermis, there are several layers of aqueous parenchyma. The vascular bundles occur in multiple rows, the peripheral row having bundles with narrower diameters than the central row. Characters related to Kranz syndrome of the chlorocyperoid type were observed. Ultrastructural features support a possible C4 pathway in this species. This work is the first citation of chloroplasts in the cells of the vascular system for the genus. In this study, it was possible to observe several important features of plants submitted to water and salt stress, such as: wax, thickened outer periclinal walls of the epidermal cells, aqueous parenchyma and Kranz syndrome

    The impact of climate change on lakes in the Netherlands: a review

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    Climate change will alter freshwater ecosystems but specific effects will vary among regions and the type of water body. Here, we give an integrative review of the observed and predicted impacts of climate change on shallow lakes in the Netherlands and put these impacts in an international perspective. Most of these lakes are man-made and have preset water levels and poorly developed littoral zones. Relevant climatic factors for these ecosystems are temperature, ice-cover and wind. Secondary factors affected by climate include nutrient loading, residence time and water levels. We reviewed the relevant literature in order to assess the impact of climate change on these lakes. We focussed on six management objectives as bioindicators for the functioning of these ecosystems: target species, nuisance species, invading species, transparency, carrying capacity and biodiversity. We conclude that climate change will likely (i) reduce the numbers of several target species of birds; (ii) favour and stabilize cyanobacterial dominance in phytoplankton communities; (iii) cause more serious incidents of botulism among waterfowl and enhance the spreading of mosquito borne diseases; (iv) benefit invaders originating from the Ponto-Caspian region; (v) stabilize turbid, phytoplankton-dominated systems, thus counteracting restoration measures; (vi) destabilize macrophyte-dominated clear-water lakes; (vii) increase the carrying capacity of primary producers, especially phytoplankton, thus mimicking eutrophication; (viii) affect higher trophic levels as a result of enhanced primary production; (ix) have a negative impact on biodiversity which is linked to the clear water state; (x) affect biodiversity by changing the disturbance regime. Water managers can counteract these developments by reduction of nutrient loading, development of the littoral zone, compartmentalization of lakes and fisheries management
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