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This study used fine-mapping to analyze genetic regions associated with bipolar disorder, identifying specific risk genes and providing new insights into the biology of the condition that may guide future research and treatment approaches.

The development of subunit vaccines mimicking the molecular complexity of attenuated vaccines has been limited by the difficulty in co-delivery of multiple chemically diverse payloads. Here, the authors report hierarchical hydrogels, assembled from a single homopolymer via a multi-stage process, that enable ratiometric loading of a protein antigen and four physicochemically distinct adjuvants.

There are no vaccines or antivirals available against enterovirus D68. Here, the authors report Jun6504 as a 2C inhibitor and show that it provides broad-spectrum antiviral activity against EV-D68, EV-A71, and CVB3 and potent antiviral efficacy in a neonatal neurological mouse model of EV-D68 infection.

Nuclear quantum effects affect chemical processes and material properties. Here the authors use path-integral molecular dynamics simulation to analyze their effects on themophysical properties of 92 organic liquids across the chemical space.

Targeting CD8⁺ T cell exhaustion is a strategy to enhance immune checkpoint inhibition and to fight cancer. Here the authors show a NRF2-dependent role for the prostaglandin I₂ receptor PTGIR in controlling T cell exhaustion.

Crystal structures of HIV Env trimer with native glycosylation in complex with neutralizing antibodies reveal a glycan shield of high-mannose and complex-type N-glycan and indicate a path for germline-targeting vaccine design.

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.

Literature produced inconsistent findings regarding the links between extreme weather events and climate policy support across regions, populations and events. This global study offers a holistic assessment of these relationships and highlights the role of subjective attribution.

This study investigates drivers of redox potential in several salt marsh sites on the basis of time series datasets. Wavelet and mutual information analyses show that the terrestrial groundwater level, rather than the marsh groundwater level, is the dominant control on redox potential.

This study reports on excavations of hearths and stone artefacts from 20,000-year-old deposits at Dargan Shelter, which at an elevation of 1,073 m is believed to be the oldest occupied high-altitude site in Australia.

A steadily growing toolbox of techniques is helping researchers to understand the structural complexity that enables RNA molecules to perform a dizzying array of functions in the cell.

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).

BRCA1 and BRCA2 are well known breast cancer predisposition genes, however, many variants have not yet been classified for their pathogenicity. Here, the authors analyse a large combined cohort to provide evidence of variant pathogenicity.

Sarcomas are a group of mesenchymal malignancies which are molecularly heterogeneous. Here, the authors develop an in vivo muscle electroporation system for gene delivery to generate distinct subtypes of orthotopic genetically engineered mouse models of sarcoma, as well as syngeneic allograft models with scalability for preclinical assessment of therapeutics.

The structure-function relationships of a β-helix, a folding motif formed by parallel β-strands arranged in a helical repetitive pattern, remain poorly understood and underexploited. Here, the authors reconstitute a protein β-helix by design from an elementary sequence of 18 amino acids, which self-assembles into a self-contained multifunctional motif exhibiting a range of biological functions.

Guided by a structure of VGLUT2 with substrate, Li et al. identify the mechanisms for selective substrate recognition, a role for lipid modification in limiting axonal dispersion and for the cytoplasmic gate in allosteric regulation by lumenal H⁺.

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.

Net-zero policies can put pressure on land use, which can conflict with preserving natural landscapes, cultural sites and agricultural areas. Now a study integrates national energy models with proactive and collaborative planning to design net-zero pathways that conserve natural capital and address diverse concerns.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

While anti-retroviral therapy (ART) helps contain HIV, whether adoptive T cell therapy further improve the prognosis is unclear. Here the authors conduct an open-label, single-arm phase 1 study to assess the safety (primary outcome) and characteristic (secondary outcome) of autologous, HIV-specific T cell therapy to find it safe to warrant further efficacy assessment.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

For architectures with local connectivity, the surface code has been the leading approach to constructing fault-tolerant logical qubits, but typically requires over 1000 physical qubits per logical qubit. Here, the authors introduce a hierarchical code that maintains the same connectivity requirements as the surface code while reducing the physical qubit overhead by up to a factor of three.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

It remains unclear why some paediatric tumours appear to have such a low mutation burden. Here, the authors shed light on this paradox by analysing Wilms tumours using high resolution and high depth sequencing approaches, finding that - due to an unusual clonal architecture - standard methods significantly underestimate the mutation burden at the cellular level.

Conditional cysteine restriction in mice causes substantial weight loss, exceeding that seen with essential amino acid restriction, by activating the integrated stress and oxidative stress responses, and by unexpectedly depleting coenzyme A, leading to metabolic inefficiency.

Genetic and physical maps for the 16 chromosomes of Saccharomyces cerevisiae are presented. The genetic map is the result of 40 years of genetic analysis. The physical map was produced from the results of an international systematic sequencing effort. The data for the maps are accessible electronically from the Saccharomyces Genome Database (SGD: http://genome-www.stanford.edu/Saccharomyces/).

Comparison of genome-wide association studies of HTT CAG repeat expansion in blood to expansion-driven clinical traits in Huntington’s disease identifies shared and distinct modifiers implicating DNA mismatch repair with tissue and cell-type specificity.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

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.

Changing characteristics of light-driven molecular motors during their action is an unsolved problem. Here, the authors propose to use coupling with photon confined in an optical cavity to manipulate the speed of rotation of molecular motors.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Filamin C is a key actin-binding protein involved in cardiomyopathies and musculoskeletal disorders. Here, Wang et al reveal that it interacts with the heat shock protein HSPB7 under biomechanical stress, forming a stable hetero-dimer which is regulated by phosphorylation.

Authors show that Antarctic glaciers deliver high particle loads to the ocean, rich in iron that is potential food for marine algae. Microscopy techniques reveal this iron interacts with carbon. Ocean tracers show this glacial iron reaches far offshore.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

In a quantum simulation of a (2+1)D lattice gauge theory using a superconducting quantum processor, the dynamics of strings reveal the transition from deconfined to confined excitations as the effective electric field is increased.

An analysis of data from 522 population-based studies encompassing 82 global regions and spanning more than a century (1920–2024) shows spatiotemporal transitions across epidemiologic stages 1 to 3 of inflammatory bowel disease, and models stage 4 progression.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

The force fields used in molecular simulations typically assign varied Lennard-Jones parameters to the atoms of a given element, depending on the neighborhood of each atom in the chemical graph of a compound, but optimizing so many parameters without overfitting is challenging. Here, the authors provide evidence that far fewer LJ parameters may be needed.