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This trial found spinal cord stimulation was well tolerated in people with gait-impaired Parkinson’s disease. It suggests that longer use improved lower-body motor symptoms while reducing thalamic hypermetabolism and cholinergic overactivity.

Large-scale genome-wide analyses identify hundreds of genetic loci associated with hypothyroidism and thyroid hormone levels, demonstrating the potential of using polygenic risk scores to predict disease onset and progression.

The authors report findings from the MOBILIZE trial, which found that exercise therapy and self-management support improved patient-reported quality of life in individuals with multiple chronic conditions.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

A combination of animal studies, data from a clinical trial and insights from an observational cohort suggest that, in individuals with metabolic dysfunction-associated steatohepatitis, semaglutide improves liver histology by reverting patient proteomes to better mimic the proteome of individuals without the disease.

Genome-wide analyses identify variants associated with infertility and reproductive hormone levels but find limited polygenic overlap between reproductive hormone levels and infertility at the population level.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

The gut hormone tachykinin (Tk) is found to be regulated by protein intake in flies and mice. In flies, Tk is shown to impact food choices, sleep and lifespan.

Soft tissue tumors in infants encompass an overlapping spectrum of diseases posing unique diagnostic and clinical challenges. Here, the authors investigate the genetic basis of cryptogenic congenital mesoblastic nephroma and infantile fibrosarcoma lacking the canonical NTRK3-ETV6 fusion gene, and identify therapeutically tractable intragenic rearrangements in EGFR and BRAF.

A high-resolution spectroscopic tool is demonstrated using the stochastically fluctuating intensity spikes in time and energy domains of a self-amplified spontaneous emission X-ray free-electron laser.

C-terminal α-amidated peptides are attractive therapeutic targets, but preparative methods to access amidated pharmaceuticals are limited both on lab and manufacturing-scale. Here, the authors report a straightforward and scalable approach to the C-terminal α-amidation of peptides and proteins from cysteine-extended polypeptide precursors.

Examining drivers of the latitudinal biodiversity gradient in a global database of local tree species richness, the authors show that co-limitation by multiple environmental and anthropogenic factors causes steeper increases in richness with latitude in tropical versus temperate and boreal zones.

“Dissolved oxygen (DO) sustains river ecosystems, but the effects of hydrological extremes remain poorly understood. Here it is shown that sudden floods cause abrupt declines in DO, suggesting that increased future flooding may lead to the degradation of aquatic ecosystems.

Endogenous retroviruses (ERV) are inherited remains of retroviruses that have colonized host genomes during evolution. Here the authors observe considerable species-specific ERV variation among Darwin’s finches, reflecting historic retrovirus-host interactions.

In mouse and nonhuman primate models, treatment with selective, long-acting neurokinin 2 receptor agonists aids weight loss by suppressing appetite and increasing energy expenditure, as well as by increasing insulin sensitivity.

Genome-wide analyses using fetal and parental genotypes identify 40 independent associations influencing placental weight and highlight the role of the fetus in preeclampsia risk and placental growth regulation via insulin signaling.

Atmospheric methane-oxidizing bacteria constitute the sole biological sink for atmospheric methane. Here, Schmider et al. assess the ability and strategies of seven methanotrophic species to grow with air as sole energy, carbon, and nitrogen source, showing that these bacteria can grow on the trace concentrations of methane, carbon monoxide, and hydrogen present in air.

Understanding the emergence, evolution, and transmission of antibiotic resistance genes (ARGs) is essential to combat antimicrobial resistance. Here, Munk et al. analyse ARGs in hundreds of sewage samples from 101 countries and describe regional patterns, diverse genetic environments of common ARGs, and ARG-specific transmission patterns.

Meta-analyses of genome-wide association studies for endometriosis identify 49 distinct association signals. Fine-mapping of causal variants explores functional effects across various tissues. Genetic correlations between endometriosis and other pain conditions are also highlighted.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

The intestine is an important immunological organ in embryonic life, preparing the infant for the microbial colonization following birth. Here authors show that between gestational weeks 14 and 22, the human foetal intestine is first populated by myeloid and innate lymphoid cells, followed by the development of lymphoid cells and a wider range of proliferation-capable immune cell types.

Genome-wide association analyses of two oral glucose tolerance test-derived measures of postprandial insulin resistance discover ten new loci. Functional characterization identifies nine candidate genes implicated in the regulation of GLUT4.

Most mammalian promoters are inherently bidirectional, but transcription only elongates productively in one direction. Data presented in this paper demonstrate that at least part of the answer lies in the asymmetric distribution of polyadenylation-site sequences around human gene promoters causing termination of upstream antisense transcription.

FRET has been used to study protein conformational changes but has never been applied to RNA aptamers. Here the authors develop a genetically encodable RNA aptamer-based FRET system on single-stranded RNA origami scaffolds, and demonstrate it can be used to study RNA conformational changes.

The transcription factor double homeobox protein (DUX) induces a totipotency-specific regulatory program, including the upregulation of DUXBL. DUXBL subsequently accesses DUX-bound regions and interacts with TRIM24 and TRIM33, thus contributing to totipotency exit.

Combining attosecond metrology and soliton dynamics in hollow-core fibres, the generation of attosecond laser pulses from the deep-ultraviolet to the near-infrared regime and the measurement of attosecond solitons with 350-as durations at optical wavelengths are demonstrated, providing an efficient route to generate intense isolated attosecond pulses complementary to those based on high-harmonic generation in gases.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Genome-wide association studies (GWAS) have become a key tool to discover genetic markers for complex traits; however, environmental factors that interact with genes are rarely considered. Here, the authors conduct a GWAS of obesity traits, and find that smoking may alter genetic susceptibilities.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

Isolation of circulating tumor cells (CTCs) allows for non-invasive disease monitoring and characterization. Here the authors describe an alternative CTC isolation method based on the ability of the malaria rVAR2 protein to specifically bind oncofetal chondroitin sulfate, which is expressed by all cancer cells

Selectivity of ligand-induced protein degradation and dimerization is conferred by plastic interprotein contacts. Computational protein–protein docking reveals the underlying interprotein contacts to inform the design of a BRD4 selective degrader.

A European ancestry genome-wide meta-analysis of pregnancy-associated bleeding traits identifies five novel loci associated with postpartum hemorrhage, but none with early bleeding. Functional analysis highlights a role for progesterone receptor-mediated signaling.

Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.

By analysing plant and nematode DNA from sites all around the Arctic, it is shown that vegetation before about 10,000 years ago contained more forbs (non-graminoid herbaceous vascular plants) than previously believed, which changes our understanding about the functioning of the diverse northern ecosystem that existed at this time.

Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. Here, using genetic data for 1.52 million individuals, the authors identify 25 genes with protein-altering variants exhibiting a strong deficit of homozygosity, suggesting they are essential for successful early development.

Multi-region sequencing of 35 primary uveal melanomas and their matched metastases yields new insights into the genetics and evolution of these tumors and provides potential biomarkers for progression and therapy.

Data from over 700,000 individuals reveal the identity of 83 sequence variants that affect human height, implicating new candidate genes and pathways as being involved in growth.

Maternal genome-wide analyses identify variants associated with gestational duration and preterm delivery. Maternal alleles positively associated with gestational duration exhibit negative fetal effects on birth weight, likely reflecting antagonistic pleiotropy.

Artificial nanopores can perform selective gating of molecules analogous to transmembrane proteins. Here, the authors design a DNA origami pore with a controllable lid for size-selective gating and translocation of macromolecules and evaluate its biosensing properties by single particle assay.

Hepatic bone morphogenetic protein 8b expression is shown to be induced in NASH to drive wound healing responses and NASH progression by promoting inflammatory pathways in hepatic stellate cells and, more broadly, in the liver parenchyma.

Following a wide-ranging review of studies, reports and policies about nature’s multiple values, combinations of values-centred approaches are proposed to improve valuation of nature, address barriers to uptake in decision-making, and make transformative changes towards more just and sustainable futures.

Establishing the relative transmissibility of emerging variants of SARS-CoV-2 is key for pandemic management. Here, the authors use full-population administrative data from Denmark linked to PCR test results and estimate that the Alpha variant was ~60% higher than other strains circulating in early 2021.