Search

SLIDE is a machine learning-based method for identification of significant latent factors across multiomics datasets.

Meltwater entering the Southern Ocean from Antarctic ice shelves varies substantially from year to year, with consequences for Southern Ocean circulation and climate, according to remote sensing estimates of ice-shelf basal melting rates.

Montserrat Garcia-Closas and colleagues report a genome-wide association study for bladder cancer. They identify three new susceptibility loci on chromosomes 22q13.1, 19q12 and 2q37.1.

Exome sequencing and copy number analysis are used to define genomic aberrations in early sporadic pancreatic ductal adenocarcinoma; among the findings are mutations in genes involved in chromatin modification and DNA damage repair, and frequent and diverse somatic aberrations in genes known as embryonic regulators of axon guidance.

Rosalind Eeles and colleagues report meta-analysis of genome-wide association studies for prostate cancer and genotyping on the custom iCOGS array in 25,074 cases and 24,272 controls from 32 studies available in the PRACTICAL Consortium. They identify 23 new prostate cancer susceptibility loci, 20 of which are associated with both aggressive and non-aggressive disease.

The authors provide a comprehensive, single base resolution view of association between genetic variation and DNA methylation in human brain. They also show that heritability attributed to schizophrenia GWAS-associated variants reflects the epigenetic plasticity of the brain.

A phase 1/2a study shows that human neural progenitor cells modified to release the growth factor GDNF are safely transplanted into the spinal cord of patients with ALS, with cell survival and GDNF production for over 3 years.

Here, the authors design a multiplex serology platform to quantitatively measure antibodies against 20 infectious agents in UK Biobank participants and confirm associations of antibody responses with sociodemographic characteristics, HLA genetic variants, and disease outcomes.

Dynamic regulation of colonic secretory cell numbers is a critical component of the response to intestinal injury and inflammation. Here, the authors show that loss of the intracellular signalling regulator Sprouty2 in the intestinal epithelial cells is a protective response to injury that leads to increased secretory cell numbers, thus limiting colitis severity.

Acute ischemic stroke impacts men and women differently. Here, the authors show how different lesion patterns in men and women are linked to the extent of stroke severity.

Whole-genome sequence analysis identifies five independent risk loci for Lewy body dementia and demonstrates overlapping genetic architecture with Alzheimer’s and Parkinson’s diseases.

The tumour microenvironment is low in glucose and high in the alternative metabolite lactate, which regulatory T cells are shown here to use, maintaining their ability to suppress effector immune cells.

Evaluating the short-term exposure to wildfire-specific fine particulate matter (PM_2.5) showed greater risks of hospitalization for all major respiratory diseases than non-wildfire PM_2.5. When developing air quality guidelines, it is also important to consider that PM_2.5 from varying sources can have different health effects, which require targeted health and environmental policy approaches.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

Several studies show that APOE-ε4 coding variants are associated with Alzheimer’s disease (AD) risk. Here, Zhou et al. perform fine-mapping of the APOE region and find AD risk haplotypes with non-coding variants in the PVRL2 and APOC1 regions that are associated with relevant endophenotypes.

Progressive diseases tend to be heterogeneous in their underlying aetiology mechanism, disease manifestation, and disease time course. Here, Young and colleagues devise a computational method to account for both phenotypic heterogeneity and temporal heterogeneity, and demonstrate it using two neurodegenerative disease cohorts.

Robert Jenkins and colleagues report fine mapping of the glioma risk region at 8q24.21. They identify a new low-frequency variant in the region that is strongly associated with risk of oligodendroglial tumors and astrocytomas with IDH1 or IDH2 mutation.

The zinc-finger-containing protein schnurri-2 is shown to regulate positive selection in T-cell development by dampening the mitochondrial death pathway.

Notch1 signalling and the dosage of the Notch1 ligand, Dll4, are critical for vascular development. Here the authors show that the transcriptional repressor, Snail1, is expressed in endothelial cells, where it regulates vascular development by downregulating Dll4 levels and Notch1 signalling during mouse embryogenesis.

Single-cell transcriptomics studies on human and mouse non-small cell lung cancer and conditional knockout mouse models show that IL-4 from bone marrow basophils drives the development of granulocyte-monocyte progenitors to myeloid cells that suppress antitumour immunity.

TARPs and GSG1L are evolutionarily- and structurally-related AMPA receptor auxiliary subunits that differ in function through unresolved mechanisms. Here, the authors provide insight into the spatiotemporal expression, composition, and functionality of GSG1L-containing protein complexes.

Wetlands store large quantities of carbon, the distribution and quantity of which is little known. Here, Nahlik and Fennessy use data collected as part of the 2011 National Wetland Condition Assessment to estimate wetland carbon stocks across the United States, illustrating total storage of 11.52 PgC.

Obesity is a global pandemic with limited treatment options. Here, the authors show evidence in mice that the mitochondrial uncoupler BAM15 effectively induces fat loss without affecting food intake or compromising lean body mass.

Joint analysis of multiple traits can increase power and provide insights into shared genetic architecture. Here, Nguyen et al. develop multi-trait TADA (mTADA), an extension of TADA (transmission and de novo association test) that jointly analyses de novo mutations of traits for improved risk-gene identification power.

Elevated inorganic phosphate levels promote excessive parathyroid hormone secretion, which contributes to the aetiology of secondary hyperparathyroidism. Here, the authors show that phosphate directly inhibits the calcium-sensing receptor, the main regulator of parathyroid hormone secretion.

Animal diversity, measured in numbers of species, is rapidly being lost to extinction. Here, Cooke et al. show that the diversity of ecological strategies employed by land mammals and birds is also expected to narrow towards small, fecund, insect-eating generalists with fast-paced life histories.

The prognosis of cancer patients with lymph node (LN) metastasis is worse than those without. Here, the authors report that while histone deacetylase 11 (HDAC11) inhibition suppresses tumor growth within the LN, it also promotes cancer cell migration out of the LN to form distant metastasis, and therefore suggest caution with HDAC inhibitors.

An approximately 2-million-year-old male Paranthropus robustus cranium from Drimolen Main Quarry in South Africa refutes influential ideas of sexual dimorphism in this taxon and instead suggests local microevolution within robust australopiths.

As part of Myeloid Cells in Neurodegenerative Disease (MyND) initiative, the authors profiled the transcriptome of primary monocytes and microglia from patients with Parkinson’s disease and controls, revealing the pathways and genes that are altered in the immune system of patients with Parkinson’s disease.

For many neurodevelopmental disorder (NDD) risk genes, the significance for mutational burden is unestablished. Here, the authors sequence 125 candidate NDD genes in over 16,000 NDD cases; case-control mutational burden analysis identifies 48 genes with a significant burden of severe ultra-rare mutations.

Chronic pain is the greatest source of disability globally and claims related to chronic pain feature in many insurance and medico-legal cases. In this Consensus Statement, a presidential task force of the International Association for the Study of Pain examines the capabilities of brain imaging in the diagnosis of chronic pain, and the ethical and legal implications of such uses of brain imaging.

An exciting genome-wide association study in the British population for seven common diseases. This analysis confirms previously identified loci and provides strong evidence for many novel disease susceptibility loci.

Profiling the resistance landscape to PRC2 inhibitors in EZH2-mutant lymphoma with CRISPR-suppressor scanning reveals drug addiction mutations and a repressive methylation ceiling. Surpassing the ceiling with SETD2 inhibition halts lymphoma growth.

The centromere is required for the segregation of chromosomes. Here, the authors report the organization and dynamic of holocentric chromosomes, each containing 7 to 11 evenly spaced megabase-sized centromere-specific histone H3-positive units.

The median eminence (ME) at the base of the brain controls body homeostasis. Here, the authors describe a functional tanycyte subpopulation at the ME which tastes the surrounding milieu, responds to metabolic signals and regulates glucose homeostasis.

Mammalian orthoreovirus causes serotype-specific disease in the brain. Here, Shang et al. identify and characterise the role of paired immunoglobulin-like receptor B in reovirus attachment, entry and infectivity in the brain.

The external globus pallidus (GPe) is a key contributor to motor suppressing pathways in the basal ganglia. The authors show that optogenetic interventions targeted to specific neuronal subpopulations in the GPe can disrupt pathological activity in the basal ganglia and restore movement for hours beyond stimulation.

Male mice exposed to PFAS (a group of environmental contaminants) have reduced sperm production but normal sperm viability & motility. Embryos created by in vitro fertilisation (IVF) with PFAS-exposed sperm have disrupted transcriptomes suggesting possible transgenerational effects.

Phylogenetic and machine learning analyses reveal that bats (order: Chiroptera) are not a group with uniform viral epidemic potential: virulence, transmissibility, and death burden cluster within distinct clades of bats.

Fewer than 100 wild Cat Ba langurs survive in Vietnam. Here, the authors use whole genome sequencing to demonstrate potential adaptations to saltwater consumption as well as maintenance of adaptive potential despite low levels of genetic diversity and high levels of inbreeding.

Ecologists must understand how marine life responds to changing local conditions, rather than to overall global temperature rise, say Amanda E. Bates and 16 colleagues.

The stability of epithelial adherens junctions depends on tension generated by actomyosin contractility. Here Lee et al. describe a novel role for the axon guidance receptor Neogenin in maintaining junctional stability by recruiting actin nucleation machinery to adherens junctions.

Genome-wide association meta-analyses of waist-to-hip ratio adjusted for body mass index in more than 224,000 individuals identify 49 loci, 33 of which are new and many showing significant sexual dimorphism with a stronger effect in women; pathway analyses implicate adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution.

A spatially resolved transcriptional atlas of the mid-gestational developing human brain has been created using laser-capture microdissection and microarray technology, providing a comprehensive reference resource which also enables new hypotheses about the nature of human brain evolution and the origins of neurodevelopmental disorders.

By taking advantage of stimulated Raman spectroscopy and fibre-laser technology, virtual histology images can be obtained in real time in the operating room, with diagnostic quality comparable with that achieved via conventional histopathology.

John Perry and colleagues report the results of a large genome-wide association study meta-analysis to identify variants influencing age at natural menopause. They identify 54 independent signals and find enrichment near genes involved in delayed puberty and DNA damage response.

Some animals and insects can change the colour of their skin, but mimicking such function in man-made materials is complex. Here, the authors demonstrate an all-solution processed chameleon-inspired stretchable e-skin capable of interactive colour changes and tactile sensing.

Demyelination failure in multiple sclerosis (MS) may contribute to the disease progression. This study shows that chondroitin sulfate proteoglycans (CSPGs) can inhibit remyelination in an animal model of MS via CSPG binding with the receptor PTPσ on oligodendrocyte progenitor cells, and disruption of this interaction can promote recovery in the animal models of MS.

Family-based study designs have been applied to resolve confounding by population stratification, dynastic effects and assortative mating in genetic association analyses. Here, Brumpton et al. describe theory and simulations for overcoming such biases in Mendelian randomization through within-family studies.