Search

Sex bias and association with smoking history identified in the landscape of driver mutations and clonal expansions in normal human bladder tissue may explain the higher bladder cancer risk in men and smokers.

There is a need forPlasmodium transmission blocking drugs for malaria elimination. Here, Miguel-Blanco et al. screen >10,000 compounds against stage V female gametocytes, identify active compounds belonging to 57 chemotypes and confirm transmission blocking activity of four selected compounds in vitro.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

The implications of early telencephalic development in cortical disorders remain elusive. Here, the authors define risk gene dynamics and perturbation effects in neural stem cells, revealing vulnerability phases during early human corticogenesis.

Drug resistance remains a major challenge in cancer treatment. Here, the authors identify Connexin43 as target that enhances BRAF/MEKi efficacy by interfering with DNA repair pathways, overcoming drug resistance. They develop an mRNA therapy that improves efficacy and sensitizes resistant cells.

A survey across 90 societies reveals that variation and change in everyday norms are explained by a single value dimension: the priority societies place on individualizing versus binding moral concerns.

This study demonstrates that growth arrest under stress in Arabidopsis protects meristem cells from DNA damage, challenging the idea that it is merely due to energy trade-offs and highlighting its role as an active defense strategy.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Actin is crucial for nervous system function yet the role of microexons in its modulation is unclear. Here, the authors show that a microexon in DAAM1 has a role in actin dynamics, neuronal function and memory formation in mice.

In 1,088 pregnant individuals, assessment of abnormal serum angiogenic factors is demonstrated to be noninferior to the standard clinical approach based on estimated fetal weight and Doppler percentiles for the identification of fetuses at a higher risk of neonatal acidosis or Cesarean delivery, thus offering a beneficial option in settings where Doppler or experienced sonographers are not readily available.

Historical ecology uses a wide and varied range of sources to investigate long-term dynamics of ecosystems, species and their traits, and different dimensions of nature–human interactions. This Perspective discusses the value of this approach for biodiversity and conservation science, and offers a strategy for the continued development of the field.

Anaplastic thyroid cancer (ATC) is a particularly aggressive cancer type with limited effective therapeutic options. Here, the authors identify the SUMO E3 ligase PIAS2 as a potential therapeutic target in ATC and mechanistically investigate its role in mitotic spindle and centrosome assembly.

Ancient DNA reveals genetic differences between stone-tool users and people associated with ceramic technology in the Caribbean and provides substantially lower estimates of population sizes in the region before European contact.

The authors present a multiomics study of type 2 diabetes and quantitative blood lipid and lipoprotein traits in Hispanic/Latino populations. They demonstrate how integrating GWAS with omics characterization can advance precision medicine.

Kdm1a is a histone demethylase implicated in intellectual disability. Here, the authors show that removing Kdm1a in neurons of the adult mouse forebrain disrupts silencing of nonneuronal genes and chromatin organization, emphasizing its role in preserving neuronal genome integrity.

Myelomagenesis progresses through well-defined pre-malignant states. Here, using single-cell RNA sequencing and T cell receptor repertoire analysis of bone marrow T cells in patients at different stages of myelomagenesis, the authors identify large clonotypic expansions characterized by the expression of multiple immune checkpoints.

By deciphering the molecular fingerprint of cells treated with host-directed therapies targeting protein translation, the authors identified a rational approach to select for broad-spectrum antivirals with potential to counteract future pandemic viruses.

Nonreceptor guanine-nucleotide exchange factors (GEFs) are emerging as important regulators of heterotrimeric G proteins. Here, the authors present structural and mechanistic insights into how a class of nonreceptor GEFs containing the Ga-Binding and Activating motif interact and modulate G proteins.

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

Ito et al. present CoVFit, an AI model that predicts variant fitness (transmissibility) from spike protein sequences alone. They further demonstrate its utility in forecasting viral evolution via single amino acid mutations.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Liu et al. demonstrate that human-driven soil contamination in natural areas mirrors that in nearby urban greenspaces globally, and highlight the potential influence that soil contaminants have on ecosystem functions.

A four-stranded DNA intermediate, known as a Holliday junction, is formed during meiosis and DNA repair. This structure covalently links two DNA molecules. The product of the RuvC gene in Escherichia coli was shown to be the bacterial Holliday junction resolvase. The mammalian enzyme has remained refractory to identification until now, where GEN1 is identified as the human resolvase.

The authors show that TET2 is recruited to chromatin by the RNA-binding protein PSPC1. PSPC1 and TET2 contribute to ERV and ERV-associated gene regulation by both transcriptional repression via histone deacetylases and post-transcriptional destabilization of ERV RNAs through 5hmC modification.

Sexual forms of malaria parasites are responsible for transmission to the mosquito. Anti-malarial drug resistance remains a serious problem and requires advent of new drug therapies. Here, the authors present a high-throughput screen of potential antimalarial compounds, identifying seventeen drug-like molecules specifically targeting transmission.

Environmental drivers of soil carbon and its sensitivity to warming are poorly understood. The authors compare soil samples of paired urban and natural ecosystems and show that under warming, the microbiome is an essential driver of soil carbon in urban greenspace compared with natural ecosystems.

A common immune signature in the blood of patients with COVID-19, who are otherwise clinically heterogeneous, sheds light into the pathogenesis and clinical progression of the disease.

Mosses support carbon sequestration, nutrient cycling, organic matter decomposition and plant pathogen control in soils across the globe, according to a global survey of soil attributes in ecosystems with and without mosses.

In a widespread sampling campaign across urban soils, the authors find that soil biodiversity, but not plant diversity, is positively related to multiple ecosystem functions in urban environments.

Hepatitis B virus (HBV) infection and DNA integration is a frequent cause of hepatocellular carcinoma (HCC), but the consequences of this process are not fully understood. Here the authors use whole-genome and long-read sequencing data from HCC patient samples to study the timing and alterations induced by HBV insertions.

Cohesin, which tethers sister chromatids together, is found to be cleaved by separase after DNA damage, resulting in cohesin dissociation and allowing for post-replicative repair of DNA double-strand breaks.

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.

Neuronal identity maintenance is highly regulated. Here, the authors showed that CBP and p300 safeguard neuronal identity through histone acetylation at promoters and enhancers of neuronal specific genes. The loss of both CBP and p300 impairs gene expression, circuit activity, and behavior in mice.

Ankylosing spondylitis is a common, highly inheritable inflammatory arthritis with poorly understood biology. Here Brown, Cortes and colleagues use fine mapping of the major histocompatibility complex and identify novel associations, and identify other HLA alleles that like HLA-B27 interact with ERAP1 variants to influence disease risk.