Spotlight on avian pathology: fowlpox virus

Fowlpox virus is the type species of an extensive and poorly-defined group of viruses isolated from more than 200 species of birds, together comprising the avipoxvirus genus of the poxvirus family. Long known as a significant poultry pathogen, vaccines developed in the early and middle years of the 20th century led to its effective eradication as a problem to commercial production in temperate climes in developed western countries (such that vaccination there is now far less common). Transmitted mechanically by biting insects, it remains problematic, causing significant losses to all forms of production (from back-yard, through extensive to intensive commercial flocks), in tropical climes where control of biting insects is difficult. In these regions, vaccination (via intra-dermal or subcutaneous, and increasingly in ovo, routes) remains necessary. Although there is no evidence that more than a single serotype exists, there are poorly-described reports of outbreaks in vaccinated flocks. Whether this is due to inadequate vaccination or penetrance of novel variants remains unclear. Some such outbreaks have been associated with strains carrying endogenous, infectious proviral copies of the retrovirus, reticulo-endotheliosis virus (REV), which might represent a pathotypic (if not newly emerging) variant in the field. Until more is known about the phylogenetic structure of the avipoxvirus genus (by more widespread genome sequencing of isolates from different species of birds) it remains difficult to ascertain the risk of novel avipoxviruses emerging from wild birds (and/or by recombination/mutation) to infect farmed poultry

Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults comprising 14 established US prospective cohort studies. Starting as early as 1971, investigators in the C4R cohort studies have collected data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R links this pre-coronavirus disease 2019 (COVID-19) phenotyping to information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute and postacute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and reflects the racial, ethnic, socioeconomic, and geographic diversity of the United States. C4R ascertains SARS-CoV-2 infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey conducted via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations and high-quality event surveillance. Extensive prepandemic data minimize referral, survival, and recall bias. Data are harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these data will be pooled and shared widely to expedite collaboration and scientific findings. This resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including postacute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term health trajectories

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

THE ADSORPTION SITE OF FORMATE (HCOO) ON COPPER SURFACES

Les études SEXAFS précédentes de la nature de formiate sur Cu(100) et Cu(110) ont conduit de différentes conclusions. En particulier la distance Cu-O sur Cu(100) est trouvée très longue (~2.3Å) et est crue comme évidence pour une bond de surface anomale. En réanalysant les deux spectres par l'utilisation de la simulation de multicoquille atomique, les résultats montrent que la structure est, en fait, très similaire pour les deux surfaces avec une distance voisine Cu-O d'environ 1.97Å, qui est similaire que celle trouvée dans le formiate de cuivre anhydre. L'assignation précédente résulte de l'échec de la filtration de Fourier de la "contribution du premier voisin'' pour séparer les effets de deux liaison similaires pour cette coquille atomique. Le problème se pose par le déplacement de la distance O-O dans le formiate et de la distance Cu-Cu à la surface qui force les atomes d'oxygène à adopter les sites d'adsorption de faible symétrie.Previous SMAFS studies of the structure of formate on Cu(100) and Cu(110) have led to very different conclusions. In particular the Cu-O distance on Cu(100) was found to be very long (~2.3Å) and believed to be evidence for an 'anomalous' surface bond. Reanalysis of both sets of data using a multishell simulation shows that the structure is, in fact, very similar on both surfaces with a Cu-O nearest neighbour distance of about 1.97Å, similiar to that in anhydrous copper formate. The previous assignment arises from the failure of the Fourier filtering of the 'nearest neighbour contribution' to resolve the effects of two similar bondlengths to this shell. The problem arises because of the mismatch of the O-O distance in formate and the Cu-Cu distance on the surface which forces the oxygen atoms to adopt low symmetry adsorption sites

THE STRUCTURE OF THE Cu(111) (√3 x √3) R30°-Cl SURFACE : A COMBINED SEXAFS AND PHOTOELECTRON DIFFRACTION STUDY

L'étude de la surface EXAFS de Cu(√3 x √3)R30°-Cl, en enregistrant le spectre du rendement total électronique au delà du seuil d'absorption - K de Cl en utilisant SRS Daresbury, montre que la distance interatomique CuCl dans cette phase est de 0.05 ± 0.02Å plus longue que celle de CuCl massif. Ce résultat est donné a la fois par l'analyse de Fourier en filtrant une seule coquille atomique at par simulation de multicoquille atomique. Les deux analyses révèlent aussi l'adsorption dans les sites creux de coordination - 3, cependant aucune de ces deux méthodes permet de faire une distinction entre deux sites, creux inéquivalents, de coordination - 3 à la surface (111) du cubic face centrée (cfc). Ces deux sites montrent que la contribution pour l'EXAFS des atomes les plus proches est identique dans toutes les directions de polarisation et diffère seulement à la troisième (et plus) coquille atomique la plus proche. Par contrast les spectres obtenus par diffraction photoélectronique pour la photoémission 1s de Cl, le long des directions [111] et [110], fournissent de claires distinctions entre ces sites en montrant que les atomes de Cl sont adsorbés dans les mêmes sites du "cfc" que la prochaine couche atomique de Cu pourrait occuper, sur les sites creux de coordination - 3 dans la couche atomique supérieure (ou extérieure) et la second du métal. La nature complémentaire de ces deux techniques dans l'enregistrement du spectre et de son analyse est clairement démontré par cette étude.A Surface EXAFS study of the Cu(√3 x √3)R30°-Cl structure, collecting data above the Cl K-edge in total electron yield on the SRS at Daresbury, indicates that the Cu-Cl distance in this phase is 0.05 ± 0.02Å longer than in bulk CuCl. This result is given by both single shell Fourier filtering analysis and by a multishell simulation treatment. Both analyses also reveal that adsorption is in a 3-fold coordinated hollow site, although neither method is able to distinguish between the two inequivalent 3-fold hollow sites present on this fcc (111) surface. These two sites show identical nearest neighbour contributions to the EXAFS at all polarisation directions, and differ only in the third (and higher) nearest neighbour shell structure. By contrast photoelectron diffraction data for the Cl 1s photoemission, collected along the [111] and [110] directions, do provide a clear distinction between these sites, showing that the Cl atoms are adsorbed in the same "fcc" sites as the next Cu atom layer would occupy, above 3-fold hollow sites in both the top and second metal atom layers. The complementary nature of these two techniques in the collection and analysis of data is highlighted by this study