Recombination is a key driver of genomic and phenotypic diversity in a Pseudomonas aeruginosa population during cystic fibrosis infection

Peer reviewe

Déclaration sur l’approche par l’archéologie sociale du changement climatique

Manifiesto sobre Arqueología Social del Cambio Climático aprobado en la Cumbre SACC celebrada en Kiel. Aprobado y firmado el 6 de septiembre de 2021.[ES] El SACC es un grupo independiente, constituido en Kiel, de investigadores e investigadoras que trabajan sobre cambio climático. El objetivo de SACC es reunir científicos y científicas internacionales y representantes de importantes organizaciones internacionales de las áreas de arqueología, paleoecología y gestión del patrimonio para con el fin de discutir y evaluar la contribución de la investigación arqueológica y paleo-ecológica para comprender la interrelación entre el cambio social, el cultural, el ecológico y el climático. Pretendemos resaltar cómo la arqueología, a través del estudio de la conducta adaptativa en el pasado, es capaz de reforzar tanto la resiliencia socio-ecológica de nuestras sociedades, como su capacidad adaptativa ante el actual cambio climático. Además, pretendemos contribuir a la comprensión del impacto del cambio climático en los yacimientos y sitios arqueológicos y patrimoniales, así como en los paisajes culturales, los museos, las colecciones y archivos patrimoniales. SACC celebrará cumbres cada dos años y emitirá una declaración o manifiesto al término de cada una de ellas. S ACC está organizada por un comité interino presidido por las personas convocantes del SACC 1.[EN] SACC is an independent group of researchers working on climate change in the past constituted in Kiel. The aim of SACC is to bring together international scientists and representatives of important international organisations in the fields of archaeology, paleoecology and heritage management to discuss and evaluate the contribution of archaeological and paleo-ecological research to understand the link between social, cultural, ecological and climatic change; and to highlight how archaeology, through the study of past adaptive behaviour, is able to enhance socio-ecological resilience of societies as well as their adaptive capacity to current climate change; furthermore, to contribute to the understanding of the impact of climate change on archaeological and heritage sites as well as on cultural landscapes, museums, collections, and archives. SACC will hold its summit every second year with a declaration at the end of each summit. SACC is organized by a steering committee chaired by the SACC 1 organisers.[FR] Le SACC est un groupe indépendant de chercheurs travaillant sur le changement climatique dans le passé, qui s’est formé à Kiel. L’objectif du S ACC est de réunir des scientifiques internationaux et des représentants d’organisations internationales importantes dans les domaines de l’archéologie, de la paléoécologie et de la gestion du patrimoine. Il a pour objectif de discuter et d’évaluer la contribution de la recherche archéologique et paléo-écologique à la compréhension du lien entre les changements sociaux, culturels, écologiques et climatiques et de souligner comment l’archéologie, par l’étude du comportement adaptatif du passé, est capable d’améliorer la résilience socioécologique des sociétés ainsi que leur capacité d’adaptation au changement climatique actuel. En outre, il contribue à la compréhension de l’impact du changement climatique sur les sites archéologiques et patrimoniaux ainsi que sur les paysages culturels, les musées, les collections et les archives. Le SACC tiendra son conseil tous les deux ans avec une déclaration à la fin de chaque conseil. Il est organisé par un comité de pilotage présidé par les organisateurs de SACC 1.Peer reviewe

Interlaboratory study for coral Sr/Ca and other element/Ca ratio measurements

The Sr/Ca ratio of coral aragonite is used to reconstruct past sea surface temperature (SST). Twentyone laboratories took part in an interlaboratory study of coral Sr/Ca measurements. Results show interlaboratory bias can be significant, and in the extreme case could result in a range in SST estimates of 7°C. However, most of the data fall within a narrower range and the Porites coral reference material JCp- 1 is now characterized well enough to have a certified Sr/Ca value of 8.838 mmol/mol with an expanded uncertainty of 0.089 mmol/mol following International Association of Geoanalysts (IAG) guidelines. This uncertainty, at the 95% confidence level, equates to 1.5°C for SST estimates using Porites, so is approaching fitness for purpose. The comparable median within laboratory error is <0.5°C. This difference in uncertainties illustrates the interlaboratory bias component that should be reduced through the use of reference materials like the JCp-1. There are many potential sources contributing to biases in comparative methods but traces of Sr in Ca standards and uncertainties in reference solution composition can account for half of the combined uncertainty. Consensus values that fulfil the requirements to be certified values were also obtained for Mg/Ca in JCp-1 and for Sr/Ca and Mg/Ca ratios in the JCt-1 giant clam reference material. Reference values with variable fitness for purpose have also been obtained for Li/Ca, B/Ca, Ba/Ca, and U/Ca in both reference materials. In future, studies reporting coral element/Ca data should also report the average value obtained for a reference material such as the JCp-1

Transglutaminase 6: a protein associated with central nervous system development and motor function.

Transglutaminases (TG) form a family of enzymes that catalyse various post-translational modifications of glutamine residues in proteins and peptides including intra- and intermolecular isopeptide bond formation, esterification and deamidation. We have characterized a novel member of the mammalian TG family, TG6, which is expressed in a human carcinoma cell line with neuronal characteristics and in mouse brain. Besides full-length protein, alternative splicing results in a short variant lacking the second β-barrel domain in man and a variant with truncated β-sandwich domain in mouse. Biochemical data show that TG6 is allosterically regulated by Ca(2+) and guanine nucleotides. Molecular modelling indicates that TG6 could have Ca(2+) and GDP-binding sites related to those of TG3 and TG2, respectively. Localization of mRNA and protein in the mouse identified abundant expression of TG6 in the central nervous system. Analysis of its temporal and spatial pattern of induction in mouse development indicates an association with neurogenesis. Neuronal expression of TG6 was confirmed by double-labelling of mouse forebrain cells with cell type-specific markers. Induction of differentiation in mouse Neuro 2a cells with NGF or dibutyryl cAMP is associated with an upregulation of TG6 expression. Familial ataxia has recently been linked to mutations in the TGM6 gene. Autoantibodies to TG6 were identified in immune-mediated ataxia in patients with gluten sensitivity. These findings suggest a critical role for TG6 in cortical and cerebellar neurons

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Genetic effects on gene expression across human tissues

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist