Search

Association analysis identifies 65 new breast cancer risk loci, predicts target genes for known risk loci and demonstrates a strong overlap with somatic driver genes in breast tumours.

Costa-Verdera et. al describe a mechanism by which AAV vector genomes activate P53-mediated signalling in CNS cells involving downstream STING activation and pro-inflammatory responses. Inhibition of either P53 or STING prevented target-cell apoptosis and inflammatory signalling.

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.

Genome-wide association analyses identify 30 risk loci for IgA nephropathy. Functional annotations of putative causal genes converge on inflammatory signaling pathways and cytokine ligand–receptor pairs, prioritizing potential new drug targets.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

Profiling transcriptional crosstalk between promoters and cell-type-specific enhancers allows large gene cargo delivery.

An analysis based on data from the Global Dietary Database shows mean animal-sourced food intakes among children and adolescents increased modestly from 1990 to two portions per day in 2018, but remain low in sub-Saharan Africa, India and Bangladesh.

The histone methyltransferase ASH1L has been linked to tumorigenesis, mainly in leukemia. Here, authors report that ASH1L cooperates with HIF-1α to induce a pro-metastatic transcriptome in prostate cancer cells, and promotes conversion of monocytes to lipid-associated tumor-associated macrophages in the bone metastatic niche.

Data on chemical concentrations in commonly recommended diets are sparse. This study estimates the association between adherence to three dietary patterns considered healthy and exposure to environmental chemicals in a multi-racial pregnancy cohort, underscoring the need for increased regulation and monitoring of environmental contaminants.

G-quadruplex stabilizers, including CX-5461, exhibit synthetic lethality with loss of BRCA1/2 in preclinical models. Here the authors report the results of a phase I study of CX-5461 in patients with solid tumors enriched for DNA-repair deficiencies.

Tommaso Grossi and colleagues propose NeuberNet, a multi-task manifold decoder that maps low-fidelity elastic displacement fields to high-resolution stress-strain in regions with sharp notches. This framework allows engineers to model plastic effects near stress raisers efficiently, improving design reliability without fully nonlinear simulations.

Montserrat Garcia-Closas and colleagues report a meta-analysis of three genome-wide association studies for estrogen receptor (ER)-negative breast cancer, including 4,193 ER-negative breast cancer cases and 35,194 controls, with replication using the iCOGS custom genotyping array in 40 studies, including 6,514 cases and 41,455 controls. They identify four loci associated with ER-negative but not ER-positive breast cancer.

Significant process has been made in using one carbon sources toward biomanufacturing. Here, the authors explore how to strength its competitiveness, and highlight latest technologies and the released patents.

In this work, the authors study the immunological and virological effects of administering either wild-type anti-HIV-1 broadly neutralizing antibodies (bNAbs) or bNAbs with a mutation that increases binding to Fc-gamma receptors (FcγRs) to rhesus macaques in the acute phase of SHIV_AD8-EO infection.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

The WAVE regulatory complex activates Arp2/3 at the cell cortex and in membrane protrusions to generate persistent cell migration. Here authors show that PPP2R1A, a scaffold subunit of protein phosphatase 2, associates with an alternative form of the WAVE complex where WAVE, the subunit that activates Arp2/3, is replaced by NHSL1.

Using JWST, more than 40 individual stars have been detected in a distant galaxy, dating back to when the Universe was only half of its current age. The stars appear to be red (super)giants that are magnified by factors of hundreds.

The nucleation of microtubules from αβ-tubulin subunits is mediated by γtubulin complexes, which vary in composition across organisms. Here, authors present the cryo-EM structure of the heterotetrameric γ-tubulin small complex (γ-TuSC) from C. albicans at near-atomic resolution.

The authors present epiScanpy: a computational framework for the analysis of single-cell epigenomic data, both ATAC-seq and DNA methylation data, with examples for clustering, cell type identification, trajectory learning and atlas integration - and show its performance in distinguishing cell types.

Using 1,854 routinely collected clinical samples from early in pregnancy, with validation in an external cohort, low-coverage cfDNA sequence data identified distinctive features among those who developed preeclampsia.

Dietary quality is reported at the global, regional and national level across 185 countries. Though diet quality increased modestly since 1990 at the global level, in South Asia and Sub-Saharan Africa it did not improve. In some regions, children’s dietary quality is lower than that of adults.

The retinal foveola in the primate eye is critical for seeing fine details, color, text and faces. Using ultrahigh-field functional magnetic resonance imaging, Qian et al discover that there is a highly specialized cortical brain region for processing foveolar information.

Current vaccines are less efficient in preventing infection. Here, the authors show that an intranasal vaccine (DelNS1-RBD) based on a live attenuated influenza virus induces robust levels of neutralizing antibodies and T cells and prevents replication of SARS-CoV-2 Delta and Omicron variants in respiratory tissues.

Study shows PTSD predisposition shares distinct genes and genomic regions with several cardiovascular conditions. Here the findings reveal neuronal, immune, and metabolic pathways, and repurposed drug targets that further the understanding of the comorbidity.

Observations of optical flares from AT2022tsd (the ‘Tasmanian Devil’) show that they have durations on the timescale of minutes, occur over a period of months, are highly energetic, are probably nonthermal and have supernova luminosities.

Minor changes to complex structures can exert major influences on synthesis strategy and functional properties but synthetic difficulties can obstruct the exploration of natural product function. Here the authors explore two parallel series of picrotoxinin analogs and identify leads with selectivity between mammalian and insect ion channels.

Engineered polyketide synthases (PKSs) have great potential as biocatalysts for the synthesis of chemically challenging molecules. Here the authors show a retrobiosynthesis approach to design and construct PKSs to produce a series of valerolactams for biopolymer production.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

Clonal hematopoiesis, which increases with age and is implicated in a variety of age-related diseases, is shown here to be associated with a greater risk of acute kidney injury and worse outcome following injury, as demonstrated using multiple patient cohorts, Mendelian randomization analysis and mechanistic studies in mouse disease models.

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.

The NIBIT-M4 trial was designed to assess the safety, biological and clinical activity of anti-CTLA4 ipilimumab with the DNA hypomethylating agent guadecitabine in advanced melanoma patients. Here the authors report the five-year follow-up results of the trial and an integrated multi-omics analysis of pre- and on-treatment tumor biopsies.

Repetto et al. provide an analysis of the genetic basis of variation of neuro-related protein levels in plasma and link this to human behaviour and disorders.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

Epichaperomes are chaperone assemblies that reorganize protein networks under stress. Here, authors reveal how HSP90 phosphorylation drives epichaperome formation, linking this process to cancer cell behaviors and pluripotent stem cell functions.

Leaf rust and stripe rust of wheat are two important fungal diseases of cultivated wheat and they are caused by infection of different pathogens. Here, the authors report the nucleotide-binding leucine-rich repeat (NLR) protein encoding gene Yr87/Lr85 confers resistance to both diseases.

The study provides a comprehensive transcriptomic atlas of the human gastrointestinal tract across the lifespan, highlighting inflammation-induced changes in epithelial stem cells that alter mucosal architecture and promote further inflammation.

A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.

Stereotactic needle biopsies are currently performed for diagnosis only in glioblastoma; this study highlights the depth of information available through multi-omics analysis.

The integration of Artificial Intelligence (AI) into Citizen Science (CS) is transforming how communities collect, analyze, and share data, offering opportunities for enhanced efficiency, accuracy, and scalability of CS projects. AI technologies such as natural language processing, anomaly detection systems, and predictive modeling are increasingly being used to address challenges like CS data validation, participant engagement, and large-scale analysis in CS projects. However, this integration also introduces significant risks and challenges, including ethical concerns related to transparency, accountability, and bias, as well as the potential demotivation of participants through automation of meaningful tasks. Furthermore, issues such as algorithmic opacity and data ownership can undermine trust in community-driven projects. This paper explores the dual impact of AI on CS. It emphasizes the need for a balanced approach where technological advancements do not overshadow the foundational principles of community participation, openness, and volunteer-driven efforts. Drawing from insights shared during a panel discussion with experts from diverse fields, this paper provides a roadmap for the responsible integration of AI into CS. Key considerations include developing standards and legal and ethical frameworks, promoting digital inclusivity, balancing technology with human capacity, and ensuring environmental sustainability.

Todorova et al. characterize the strategies through which embryos secure amino acid supply during the early phases of development. Their findings show that, in the preimplantation phase, embryos uptake whole proteins through macropinocytosis and, over time, they shift towards soluble amino acid uptake. This strategy may contribute to protecting embryos from nutrient fluctuations.

This study finds that decision markets can be a useful tool for selecting studies for replication. For a sample of 26 online experiments published in PNAS selected by a decision market, the authors find replication rates ranging between 54% and 62%.

Anna Andersson, Tanja Gruber, James Downing and colleagues report a genomic analysis of infant acute lymphoblastic leukemias with MLL rearrangements. They identify recurrent activating mutations in tyrosine kinase, phosphatidylinositol 3-kinase and RAS pathway genes but find that these mutations were often present in minor subclones and lost at the time of relapse.

Multi-ancestry genome-wide association analyses and systematic variant-to-gene mapping strategies implicate new genes and pathways influencing lung function and chronic obstructive pulmonary disease risk.

Many interactions between viral and host proteins are mediated by short peptide motifs. Here, using a phage-based viral peptide library, the authors identify 269 peptide-based interactions for 18 coronaviruses, including an interaction between SARS-CoV-2 N and G3BP1/2 that affects stress granules.

The 24-hour circadian clocks in cartilage and intervertebral disc play key roles in regulating tissue physiology, yet how they are reset on a daily basis remains elusive. Here the authors show that daily patterns of mechanical loading and associated changes in osmolarity provide a tissue-type specific entrainment time cue for these skeletal clocks.