Antiretroviral therapy and the prevalence and incidence of diabetes [2] (multiple letters)

In the study by Brown et al,1 the authors did not mention several limitations that might have an important impact on the interpretation of the results. First, the study only included men, who were mostly white (approximately 86%). Therefore, the results cannot be extrapolated to women and other ethnic groups. Second, the family history of diabetes was not ascertained in the study participants, and this could have confounded the magnitude of differences in prevalence and incidence of diabetes between the 2 study groups. Third, the reported prevalence and incidence rates of diabetes were likely to be overestimated because the diagnosis of diabetes was not confirmed by a repeated measurement of fasting plasma glucose

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

Evolution of human chromosome 7: new information from the mapping of Williams-Beuren locus on non-human primates chromosomes

Human chromosome 7 (HSA7) derives, by a pericentric inversion and a paracentric inversion, from an ancestral chromosome homologous to chromosome 10 of Pongo pygmaeus (the Asiatic Orang-Utan). Nevertheless the genesis of this autosome during primates evolution is not clear. Even if chromosome painting shows that HAS 7 synteny is highly conserved, GTG-banding comparison in Hominoidea and Cercopithecoidea indicates the probable occurrence of complex rearrangements during the evolution. In this study we used a single locus FISH approach, a powerful tool to detect fine rearrangements, in order to investigate the evolution of HAS 7. We report the chromosome mapping of Williams-Beuren syndrome locus (WS - HSA 7q11.23) on Macaca fascicularis (MFA), Cercopithecus (Chlorocebus) aethiops (CAE) and Trachypithecus cristatus (TCR) (Cercopithecoidea, Primates). The probe hybridises on all species tested and demonstrates the occurrence of rearrangements like fusion, fission and pericentric plus paracentric inversions respectively in MFA, CAE and TCR. Together with the first chromosome mapping of WS locus in Cercopithecoidea, this study confirms that single locus mapping is a very efficacious tool for the analysis of chromosomal rearrangements as it gave the opportunity to have a fine molecular confirmation to proposed banding patterns homologies

Advanced materials development for fossil energy conversion applications

Research activities being conducted as part of this project include: (1) fundamental studies of electrochemical processes occurring at surfaces and interfaces in fuel cells, and (2) development of novel materials synthesis and processing methodologies for fossil energy conversion applications. Complex impedance and dc polarization studies of the electrocatalytic activity at the cathode have allowed intrinsic materials properties to be separated from extrinsic properties related to morphology. Mixed conduction in cathode materials was shown to dramatically enhance electrocatalytic activity with this approach. Combustion synthesis methods were used to prepare multicomponent perovskite catalysts in the La{sub 1-x}Sr{sub x}Co{sub 1-y}Fe{sub y}O{sub 3} system. Electronic properties of these catalysts can be altered by adjusting the composition, which affects both catalytic activity and selectivity. Inverse micelles have been utilized to prepare nanosized nickel sulfide particles, which show promise as hydrodesulfurization catalysts for liquefied coal. Self-assembling organic monolayers and derivatized inorganic surfaces have been used to control nucleation and crystal morphology of inorganic phases