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Climate change can alter when and how animals grow, breed, and migrate, but it is unclear whether this allows populations to persist. This global study shows that shifts in seasonal timing are key to helping vertebrate species maintain population growth under global warming.

A newly discovered fossil from the Cretaceous of Belgium is the oldest modern bird ever found, showing a unique combination of features and suggesting attributes shared by avian survivors of the end-Cretaceous extinction.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Antimicrobial resistance genes that have been mobilized between bacterial species represent a subset of the naturally occurring resistome. Here, the authors compare the abundance, diversity and geographical patterns of acquired resistance genes with latent resistance genes in global sewage metagenomes.

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.

A large empirical assessment of sequence-resolved structural variants from 14,891 genomes across diverse global populations in the Genome Aggregation Database (gnomAD) provides a reference map for disease-association studies, population genetics, and diagnostic screening.

A genomic constraint map for the human genome constructed using data from 76,156 human genomes from the Genome Aggregation Database shows that non-coding constrained regions are enriched for regulatory elements and variants associated with complex diseases and traits.

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

A new taxon of toothed Late Cretaceous ornithurine preserving a pterygoid is reported, overturning assumptions about the nature of the ancestral crown bird skull.

Using microcomputed tomographic scans, whole-skeletal reconstruction of the tiny Scleromochlus taylori from the early Late Triassic of Scotland reveals new anatomical details, identifying it as a cousin of pterosaurs.

Exome sequencing data from 60,706 people of diverse geographic ancestry is presented, providing insight into genetic variation across populations, and illuminating the relationship between DNA variants and human disease.

Creating accurate digital twins and controlling nonlinear systems displaying chaotic dynamics is challenging due to high system sensitivity to initial conditions and perturbations. The authors introduce a nonlinear controller for chaotic systems, based on next-generation reservoir computing, with improved accuracy, energy cost, and suitable for implementation with field-programmable gate arrays.

Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

The APOE4 allele is a major genetic risk factor for the development of late-onset Alzheimer’s disease (AD). In this manuscript, Butovsky and colleagues suggest that APOE4 impairs the microglial response in AD by inducing TGFβ-mediated checkpoints.

Phagocytic activity of macrophages is reduced in HIV-1-infected patients, but the reason for this is unknown. Here, the authors report that secreted Tat protein inhibits phagocytosis by binding to the phospholipid PI(4,5)P₂and impairing the recruitment of small GTPase Cdc42 to the phagocytic cup.

Roger Milne and colleagues conduct a genome-wide association study for estrogen receptor (ER)-negative breast cancer combined with BRCA1 mutation carriers in a large cohort. They identify ten new risk variants and find high genetic correlation between breast cancer risk for BRCA1 mutation carriers and risk of ER-negative breast cancer in the general population.

Multiple transcriptome approaches, including single-cell sequencing, demonstrate that escape from X chromosome inactivation is widespread and occasionally variable between cells, chromosomes, and tissues, resulting in sex-biased expression of at least 60 genes and potentially contributing to sex-specific differences in health and disease.

Multi-nucleotide variants (MNV) are genetic variants in close proximity of each other on the same haplotype whose functional impact is difficult to predict if they reside in the same codon. Here, Wang et al. use the gnomAD dataset to assemble a catalogue of MNVs and estimate their global mutation rate.

A silicon-based membrane with functionalized nanopores offers significant advantages as a proton-exchange membrane for fuel cells.

Upstream open reading frames (uORFs), located in 5’ untranslated regions, are regulators of downstream protein translation. Here, Whiffin et al. use the genomes of 15,708 individuals in the Genome Aggregation Database (gnomAD) to systematically assess the deleteriousness of variants creating or disrupting uORFs.

A novel variant annotation metric that quantifies the level of expression of genetic variants across tissues is validated in the Genome Aggregation Database (gnomAD) and is shown to improve rare variant interpretation.

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.

Empirically based models of disease progression in familial frontotemporal dementia reveal the relative ordering of clinical, neuroimaging, and fluid biomarker changes and facilitate novel clinical trial designs

Reservoir computers are artificial neural networks that can be trained on small data sets, but require large random matrices and numerous metaparameters. The authors propose an improved reservoir computer that overcomes these limitations and shows advantageous performance for complex forecasting tasks

Mirrors that demonstrate 98% reflectivity and withstand 10 kilowatts of focused continuous-wave laser light are created by nanoscale fabrication of single-crystal diamond. The work finds applications in medicine, defence, industry, and communications.

These authors report and analyse the draft genome sequence of the demosponge Amphimedon queenslandica. Sponges lie on the earliest branching lineage in the animal kingdom and thus have been important in studies of the origins of multicellularity. Comparative genomic analyses presented here provide significant insights into evolutionary origins of genes and pathways related to the hallmarks of metazoan multicellularity and to cancer biology.

The use of PET for detection of Aβ in the brain in AD has limitations; studies also indicate that retinal changes, including Aβ deposition, occur in AD. Here the authors demonstrate the potential to use in vivo retinal hyperspectral imaging as a surrogate for brain accumulation of Aβ.

The synthetic-diploid (Syndip) benchmark dataset, constructed from two fully homozygous long-read assemblies, provides more accurate assessments of error rates in small-variant-calling algorithms than existing benchmarks.

In this largest whole-exome sequencing study of epilepsies to date, the Epi25 Collaborative identified extremely rare variants that confer risk for diverse epilepsy subtypes, highlighting roles in synaptic transmission and neuronal excitability.

The pituitary gland plays important roles in the regulation of key physiological functions. Here the authors provide a multiomics atlas including transcriptome, chromatin accessibility, and methylation status of over 70,000 single nuclei (sn) from mouse pituitaries.

Variations in cell shape must be accommodated by the cell membrane, but how the membrane adjusts to changes in area and volume is not known. Here the authors show that the membrane responds in a nearly instantaneous, purely physical manner involving the flattening or generation of membrane invaginations.

Evidence for multicellular life before 1.6–1.0 billion years ago is scarce and controversial. Here the authors report organized, macroscopic structures from Gabon that date to 2.1 billion years ago, have a consistent structure and seem to show evidence of multicellular colonial organization. Coming not long after the rise in atmospheric oxygen concentration, these fossils might be considered harbingers of the multicellular life that drastically expanded about a billion years later.

Computed tomography and phylogenetic analysis of the Eunotosaurus africanus skull suggests that not only is Eunotosaurus an early relative of the group that eventually evolved into turtles, but that it is also a diapsid caught in the act of evolving towards a secondarily anapsid state.

The trioxacarcins are polyoxygenated natural products that potently inhibit the growth of cultured human cancer cells. Here, the syntheses of trioxacarcin A, DC-45-A1 and structural analogues are described — the majority of which were found to be active in antiproliferative assays. A convergent, component-based route comprising sequential stereoselective glycosylation reactions allows assembly of these analogues in 11 steps or fewer.

Analysis of predicted loss-of-function variants from 125,748 human exomes and 15,708 whole genomes in the Genome Aggregation Database (gnomAD) provides a roadmap for human ‘knockout’ studies and a guide for future research into disease biology and drug-target selection.

A new method for slowing down light pulses while minimizing pulse distortion could help create practical photonic devices that route bits of information in optical-telecommunication systems.

Whole-genome sequencing analyses of African populations provide insights into continental migration, gene flow and the response to human disease, highlighting the importance of including diverse populations in genomic analyses to understand human ancestry and improve health.

The developing pelvis in birds revisits its dinosaurian state before transitioning to the characteristic avian form, providing evidence of terminal addition during evolution.