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The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
Unique features of a global human ectoparasite identified through sequencing of the bed bug genome
(2016)
The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host–symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human–bed bug and symbiont–bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite.
It is no accident that the figuration of rewriting as copying is an image from "One Way Street". This apparently casual assemblage of small, rather belletristic texts - still some of the least explored terrain in all of Benjamin - is in important ways the key to all of Benjamin’s later writing, and especially that writing based on the form of the "Denkbild" or figure of thought. In what follows, I will concentrate on one set of paired examples in order to demonstrate in a more focused way the practice of rewriting and its effects: on the relationship between "Berlin Childhood around 1900" and "One Way Street".
Der Literatur- und Medienwissenschaftler Michael W. Jennings stellt in seinem Aufsatz die Bedeutung des theologischen Konzepts der 'apokatastasis' in Benjamins Texten heraus, das sich auf Origines' Lehre von der Wiederherstellung der Dinge am Ende der Zeiten bezieht. Nach Jennings basiert Benjamins Vorstellung, dass es in der Gegenwart noch keine Religion geben kann, auf der Überzeugung, dass die Bedingungen für die Möglichkeit von Religion erst nach dem Ende der Geschichte gegeben sind. In einem zweiten Schritt geht er den verborgenen Spuren des Konzepts der 'apokastastasis' in Benjamins medientheoretischen Schriften nach. Er zeigt, wie die im Kunstwerk-Aufsatz artikulierte Hoffnung, dass die vom Kapitalismus deformierten Wahrnehmungsformen durch eine revolutionäre Veränderung der Wahrnehmung zerstört und durch eine neue Sicht auf die Welt ersetzt wird, auf die Idee der 'apokastasis' zurückgeführt werden kann.
The three 'Materialienbände' - 'Schnitte'; 'Rom, Blicke'; and 'Erkundungen für die Präzisierung des Gefühls für einen Aufstand' - that Rolf Dieter Brinkmann produced in the early 1970s have, in the last decade, gradually come to be recognized as central statements of a radically new cultural formation. A peculiar feature of this recognition, though, is the relative puzzlement that lingers over the question as to the 'form' of these volumes. That the three objects resist generic classification is by now a truism of the Brinkmann literature; yet even the construction of a cultural field within which the volumes might be compared to other works has remained elusive. The essay that follows, based largely on a reading of 'Rom, Blicke', is an attempt to construct precisely that cultural field.
We use observations of total particle number concentration at 36 worldwide sites and a global aerosol model to quantify the primary and secondary sources of particle number. We show that emissions of primary particles can reasonably reproduce the spatial pattern of observed condensation nuclei (CN) (R2=0.51) but fail to explain the observed seasonal cycle at many sites (R2=0.1). The modeled CN concentration in the free troposphere is biased low (normalised mean bias, NMB=−88%) unless a secondary source of particles is included, for example from binary homogeneous nucleation of sulfuric acid and water (NMB=−25%). Simulated CN concentrations in the continental boundary layer (BL) are also biased low (NMB=−74%) unless the number emission of anthropogenic primary particles is increased or an empirical BL particle formation mechanism based on sulfuric acid is used. We find that the seasonal CN cycle observed at continental BL sites is better simulated by including a BL particle formation mechanism (R2=0.3) than by increasing the number emission from primary anthropogenic sources (R2=0.18). Using sensitivity tests we derive optimum rate coefficients for this nucleation mechanism, which agree with values derived from detailed case studies at individual sites.
We synthesised observations of total particle number (CN) concentration from 36 sites around the world. We found that annual mean CN concentrations are typically 300–2000 cm -3 in the marine boundary layer and free troposphere (FT) and 1000–10 000 cm -3 in the continental boundary layer (BL). Many sites exhibit pronounced seasonality with summer time concentrations a factor of 2–10 greater than wintertime concentrations. We used these CN observations to evaluate primary and secondary sources of particle number in a global aerosol microphysics model. We found that emissions of primary particles can reasonably reproduce the spatial pattern of observed CN concentration (R2=0.46) but fail to explain the observed seasonal cycle (R2=0.1). The modeled CN concentration in the FT was biased low (normalised mean bias, NMB=& -88%) unless a secondary source of particles was included, for example from binary homogeneous nucleation of sulfuric acid and water (NMB= -25%). Simulated CN concentrations in the continental BL were also biased low (NMB= -74%) unless the number emission of anthropogenic primary particles was increased or a mechanism that results in particle formation in the BL was included. We ran a number of simulations where we included an empirical BL nucleation mechanism either using the activation-type mechanism (nucleation rate, J, proportional to gas-phase sulfuric acid concentration to the power one) or kinetic-type mechanism (J proportional to sulfuric acid to the power two) with a range of nucleation coefficients. We found that the seasonal CN cycle observed at continental BL sites was better simulated by BL particle formation (R2=0.3) than by increasing the number emission from primary anthropogenic sources (R2=0.18). The nucleation constants that resulted in best overall match between model and observed CN concentrations were consistent with values derived in previous studies from detailed case studies at individual sites. In our model, kinetic and activation-type nucleation parameterizations gave similar agreement with observed monthly mean CN concentrations.