Blood Group Distribution in Switzerland - a Historical Comparison.

BACKGROUND Ethnicities differ in prevalence of blood groups and antigens. Substantial donor-recipient mismatch within mixed-ethnic societies may render certain recipients at higher risk for alloimmunization. Data regarding antigen distribution within Switzerland by ethnicity is limited. We examined immigration patterns against the distribution of ABO blood groups using large cross-sectional Swiss samples spanning 70 years. METHODS Historical ABO blood group distribution data (1940-1945) from Swiss army personnel (n = 275,664) were sourced from the literature. Recent blood group phenotypes of 122,925 individuals who presented themselves at army recruitment centers (2004-2015) were obtained, alongside a validation sample of 175,202 patients from a university hospital. Two-sample tests with z-statistics assessing blood groups between samples were used. RESULTS The respective proportions of A (47.2% and 45.2%), B (8.4% and 9.8%), and AB (3.0 and 4.1) in the historical and recent army samples were significantly different (p < 0.001), while group O was not. Conclusion: ABO blood groups in Switzerland have remained stable despite substantial immigration with a changing foreign-national profile. Further research is needed to improve the understanding of antigen differences in newly introduced ethnic groups. Blood product requirements and public health initiatives aimed at recruiting blood donors would benefit from this information

Identification of tolerated insertion sites in poliovirus non-structural proteins

Insertion of nucleotide sequences encoding “tags” that can be expressed in specific viral proteins during an infection is a useful strategy for purifying viral proteins and their functional complexes from infected cells and/or for visualizing the dynamics of their subcellular location over time. To identify regions in the poliovirus polyprotein that could potentially accommodate insertion of tags, transposon-mediated insertion mutagenesis was applied to the entire nonstructural protein-coding region of the poliovirus genome, followed by selection of genomes capable of generating infectious, viable viruses. This procedure allowed us to identify at least one site in each viral nonstructural protein, except protein 2C, in which a minimum of five amino acids could be inserted. The distribution of these sites is analyzed from the perspective of their protein structural context and from the perspective of virus evolution

Structural Basis for Antiviral Inhibition of the Main Protease, 3C, from Human Enterovirus 93 ▿

Members of the Enterovirus genus of the Picornaviridae family are abundant, with common human pathogens that belong to the rhinovirus (HRV) and enterovirus (EV) species, including diverse echo-, coxsackie- and polioviruses. They cause a wide spectrum of clinical manifestations ranging from asymptomatic to severe diseases with neurological and/or cardiac manifestations. Pandemic outbreaks of EVs may be accompanied by meningitis and/or paralysis and can be fatal. However, no effective prophylaxis or antiviral treatment against most EVs is available. The EV RNA genome directs the synthesis of a single polyprotein that is autocatalytically processed into mature proteins at Gln↓Gly cleavage sites by the 3C protease (3Cpro), which has narrow, conserved substrate specificity. These cleavages are essential for virus replication, making 3Cpro an excellent target for antivirus drug development. In this study, we report the first determination of the crystal structure of 3Cpro from an enterovirus B, EV-93, a recently identified pathogen, alone and in complex with the anti-HRV molecules compound 1 (AG7404) and rupintrivir (AG7088) at resolutions of 1.9, 1.3, and 1.5 Å, respectively. The EV-93 3Cpro adopts a chymotrypsin-like fold with a canonically configured oxyanion hole and a substrate binding pocket similar to that of rhino-, coxsackie- and poliovirus 3C proteases. We show that compound 1 and rupintrivir are both active against EV-93 in infected cells and inhibit the proteolytic activity of EV-93 3Cpro in vitro. These results provide a framework for further structure-guided optimization of the tested compounds to produce antiviral drugs against a broad range of EV species

Body size and allometric variation in facial shape in children

Objectives: Morphological integration, or the tendency for covariation, is commonly seen in complex traits such as the human face. The effects of growth on shape, or allometry, represent a ubiquitous but poorly understood axis of integration. We address the question of to what extent age and measures of size converge on a single pattern of allometry for human facial shape.Methods: Our study is based on two large cross-sectional cohorts of children, one from Tanzania and the other from the United States (N57,173). We employ 3D facial imaging and geometric morphometrics to relate facial shape to age and anthropometric measures.Results: The two populations differ significantly in facial shape, but the magnitude of this difference is small relative to the variation within each group. Allometric variation for facial shape is similar in both populations, representing a small but significant proportion of total variation in facialshape. Different measures of size are associated with overlapping but statistically distinct aspects of shape variation. Only half of the size-related variation in facial shape can be explained by the first principal component of four size measures and age while the remainder associates distinctly with individual measures.Conclusions: Allometric variation in the human face is complex and should not be regarded as a singular effect. This finding has important implications for how size is treated in studies of human facial shape and for the developmental basis for allometric variation more generally.Fil: Larson, Jacinda R.. University of Calgary; CanadáFil: Manyama, Mange F.. Catholic University Of Health And Allied Sciences; TanzaniaFil: Cole, Joanne B.. Broad Institute of MIT and Harvard; Estados UnidosFil: Gonzalez, Paula Natalia. Universidad Nacional de La Plata; ArgentinaFil: Percival, Christopher J.. Stony Brook University; Estados UnidosFil: Liberton, Denise K.. National Institutes of Health; Estados UnidosFil: Ferrara, Tracey M.. University of Colorado School of Medicine; Estados UnidosFil: Riccardi, Sheri L.. University of Colorado School of Medicine; Estados UnidosFil: Kimwaga, Emmanuel A.. University of Health and Allied Science; TanzaniaFil: Mathayo, Joshua. University of Health and Allied Science; TanzaniaFil: Spitzmacher, Jared A.. University of Alberta; CanadáFil: Rolian, Campbell. University of Calgary; CanadáFil: Jamniczky, Heather A.. University of Calgary; CanadáFil: Weinberg, Seth M.. University of Pittsburgh; Estados UnidosFil: Roseman, Charles C.. University of Illinois; Estados UnidosFil: Klein, Ophir. University of California San Francisco; Estados UnidosFil: Lukowiak, Ken. University of Calgary; CanadáFil: Spritz, Richard A.. University of Colorado School of Medicine; Estados UnidosFil: Hallgrimsson, Benedikt. University of Calgary; Canad