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The gut microbiome is causally linked to body weight in preclinical models. Here, in a controlled feeding study, the authors show that greater delivery of gut-microbiome fermentable dietary substrates to the colon leads to a net negative energy balance that is accompanied by robust microbial and host responses.

Andrew Morris, Mark McCarthy, Michael Boehnke and colleagues report a meta-analysis of genome-wide association studies for type 2 diabetes, including 26,488 cases and 83,964 controls from populations of European, east Asian, south Asian and Mexican and Mexican American ancestry. They identify seven loci newly associated with type 2 diabetes and examine the genetic architecture of disease across populations.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

A strategy for inferring phase for rare variant pairs is applied to exome sequencing data for 125,748 individuals from the Genome Aggregation Database (gnomAD). This resource will aid interpretation of rare co-occurring variants in the context of recessive disease.

Genome-wide analyses in over one million self-reported cases and controls identify genetic variants associated with stuttering and find genetic correlations with autism, depression and impaired musical rhythm, supporting a potential neurological basis for stuttering.

The spike protein of the Omicron variant of SARS-CoV-2 has a higher affinity for ACE2 than Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic and vaccine-elicited neutralizing antibodies.

The light-sensitive LOV domain was engineered into the TurboID enzyme, creating ‘LOV-Turbo’. LOV-Turbo enables optogenetic control over proximity labeling, increasing the spatiotemporal precision of this technique.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

African trypanosome infections can persist for years, but immune evasion mechanisms are not fully understood. Here, Macleod et al. identify a trypanosome receptor for mammalian factor H, a negative regulator of the alternative complement pathway, that increases parasite transmission to tsetse flies.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

X-ray polarimetry observations with the Imaging X-ray Polarimetry Explorer constrain the accretion geometry in an X-ray pulsar and provide evidence for a misalignment of the spin, magnetic and orbital axes in Her X-1.

The structure of a transferrin receptor from the parasite Trypanosoma brucei in complex with human transferrin helps to understand how the parasite can use surface exposed receptors to acquire nutrients during infection while avoiding host immune detection.

A catalogue of predicted loss-of-function variants in 125,748 whole-exome and 15,708 whole-genome sequencing datasets from the Genome Aggregation Database (gnomAD) reveals the spectrum of mutational constraints that affect these human protein-coding genes.

Genome-wide analyses identify variants associated with sinus node dysfunction, distal conduction disease and pacemaker implantation, implicating ion channel function, cardiac developmental programs and sarcomeric structure in bradyarrhythmia susceptibility.

Risk variants of APOL1 associated with human chronic kidney disease have been identified, but causality has been unclear. Transgenic expression in mice now shows that such alleles can indeed cause renal disease.

To address the question of whether a recurrent tumour is genetically similar to the tumour at diagnosis, the evolution of medulloblastoma has been studied in both an in vivo mouse model of clinical tumour therapy as well as in humans with recurrent disease; targeted tumour therapies are usually based on targets present in the tumour at diagnosis but the results from this study indicate that post-treatment recurring tumours (compared with the tumour at diagnosis) have undergone substantial clonal divergence of the initial dominant tumour clone.

The occlusion of biomacromolecules can endow biominerals with enhanced mechanical properties. Here, the authors usein situatomic force microscopy and micromechanical simulations to trace micelle incorporation in calcite to shed light on the mechanism of occlusion and cavity formation.

A ‘mouse atlas’, comprising single-cell transcriptomic data from more than 100,000 cells from 20 organs and tissues, has been created as a resource for cell biology.

By demonstrating a computational approach to restore the clinical efficacy of a COVID-19 antibody, the potential to rapidly update clinical antibodies is explored.

To test the effect of transcription-generated torsional stress on nucleosome dynamics and RNA polymerase II (Pol II) kinetics in Drosophila cells, a new study reports a genome-wide sequencing-based assay to measure torsional states at the gene level. Inhibition of topoisomerases leads to rapid accumulation of torsional strain accompanied by changes in Pol II kinetics and destabilization of nucleosomes.

The human lipopolysaccharide receptor caspase-4 captures its cytokine substrate pro-IL-18 via a mechanism that is distinct from known caspase–substrate interactions, leading to inflammasome-independent IL-18 release from macrophages.

Genome-wide association analyses based on whole-genome sequencing and imputation identify 40 new risk variants for colorectal cancer, including a strongly protective low-frequency variant at CHD1 and loci implicating signaling and immune function in disease etiology.

The second Keystone Symposium on AAA+ proteins, “AAA+ Proteins: From Atomic Structures to Organisms”, was held in Tahoe City, USA in January 2020. The program highlighted recent advances from structural, biochemical and cellular approaches that have extended our understanding of these important ATP-driven molecular machines.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

Here, the authors describe the global distribution of crAssphage, its presence in Old-World and New-World primates, and its association with gut bacterial communities and dietary factors, providing insights into the origin, evolution and epidemiology of human gut crAssphage.

A genome-wide association study identifies 17 genetic loci that are associated with the risk of myeloproliferative neoplasms (MPNs), and shows that the modulation of haematopoietic stem cell function drives MPN risk.

The route of vaccine administration is known to effect the induction of immune response and the quality of such immunity. Here the authors show that intradermal but not intramuscular vaccination using live-attenuated vaccinia-based SHIV vaccine confers protection in the SHIV model in female macaques and characterise the induced immune response.

Spatial molecular imaging analysis of human pancreatic adenocarcinomas describes multicellular neighborhoods in the tumor microenvironment. Ligand–receptor analysis using optimal transport-based SCOTIA identifies interleukin-6 as a mediator of chemoresistance.

Pooling participant-level genetic data into a single analysis can result in variance stratification, reducing statistical performance. Here, the authors develop variant-specific inflation factors to assess variance stratification and apply this to pooled individual-level data from whole genome sequencing.

Tumour-infiltrating group 2 innate lymphoid cells prime CD8⁺ T cells and amplify the anti-tumour effects of PD-1 blockade in pancreatic ductal adenocarcinoma.

Different functional variants in ADH1B (and elsewhere) in Europeans and Africans strongly affect risk for alcohol dependence. Dependence only partly genetically correlates with consumption, with strong correlations to other psychiatric disorders.

The kinase regulatory-loop binding (KRLB) region of insulin receptor substrate 2 was originally thought to be a new type of domain with binding properties similar to phosphotyrosine binding (PTB) domains. A crystallographic study now shows that KRLB is actually a short peptide segment that binds to the insulin receptor using an extended series of contacts that mimic both autoinhibitory loop and ATP binding to its catalytic cleft.