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De novo and inherited dominant variants in genes encoding U4 and U6 small nuclear RNAs are identified in individuals with retinitis pigmentosa. The variants cluster at nucleotide positions distinct from those implicated in neurodevelopmental disorders.

piR48444 targets METTL7A to inhibit BMP2 mRNA m6A methylation and METTL7A/eIF4E complex-mediated BMP2 mRNA stability and translation, ultimately inhibiting osteogenic differentiation of MSCs and bone regeneration.

Here, Dillard and Taft-Benz et al. show in a female mouse model how different adjuvants affect inactivated vaccine-mediated protection against homologous SARS-CoV-2 and heterologous SARS-CoV-1-like coronaviruses. They find that an aluminum hydroxide-adjuvanted vaccine can increase risk of adverse outcomes during heterologous infection.

This prespecified updated survival and exploratory subgroup efficacy analysis of the phase 3 DESTINY-Breast04 trial shows that trastuzumab deruxtecan treatment in patients with HER2-low metastatic breast cancer leads to continuous survival benefit irrespective of estrogen receptor or hormone receptor status.

Determining the feasibility of intergrowths between zeolites is investigated using high-throughput atomistic simulations and experimental verification. Interfacial energy is an effective descriptor for identifying the feasibility of zeolite intergrowths and a zincosilicate zeolite intergrowth with three and nine rings is realized by hydrothermal syntheses.

IFNγ signalling has been described as a potential driver of resistance to immune checkpoint blockade (ICB) therapy. Here the authors report that PARP14 is upregulated in chronic IFNγ-treated cancer cell models and that its inhibition restores response to anti-PD-1 therapy in preclinical cancer models.

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

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.

Using more than 100 independent iPSC lines derived from patients with Alzheimer’s disease, the authors discovered loci associated with the neuronal production of amyloid β and confirmed their influence using RNA interference.

Bipolar membranes are increasingly being applied in a variety of electrochemical devices, yet understanding of how they operate in complex electrolyte environments is still limited. Here the authors outline a mechanistic model to explain the behaviour of bipolar membranes in forward bias polarization in mixed electrolytes.

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 analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

The authors identify V-161, a compound that inhibits enterococcal Na⁺-V-ATPase and reduces VRE colonization in mice. The high-resolution structure of V-161 reveals its action on the Na+ transport pathway, offering new therapeutic insights.

Intense, short-pulse laser irradiation generates energetic electrons that heat targets to extreme conditions relevant to laser fusion. Here, authors used an X-ray Free Electron Laser to perform spatiotemporal measurements in solid-density copper foil with sub-micron and femtosecond resolutions.

Carbon-neutral hydrogen can be produced through photocatalytic water splitting, as demonstrated here with a 100-m² array of panel reactors that reaches a maximum conversion efficiency of 0.76%.

Genome-wide association and fine-mapping analyses in approximately 260,000 Japanese individuals combined with a newly constructed Japanese-specific genotype reference panel identify hundreds of new loci and putative causal variants for 63 quantitative traits.

Douglas Easton, Per Hall and colleagues report meta-analyses of genome-wide association studies for breast cancer, including 10,052 cases and 12,575 controls, followed by genotyping using the iCOGS array in an additional 52,675 cases and 49,436 controls from studies within the Breast Cancer Association Consortium (BCAC). They identify 41 loci newly associated with susceptibility to breast cancer.

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.

Here, the authors develop a PMO-based heteroduplex oligonucleotide technology that enhances PMO delivery to tissues and normalizes motor/cardiac function and CNS symptoms in a mouse model of Duchenne muscular dystrophy.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

Hayabusa2 created an artificial crater on Ryugu to analyse the subsurficial material of the asteroid. Results show that the subsurface is more hydrated than the surface. It experienced alteration processes that can be traced back to Ryugu’s parent body.

The dopamine D₂ receptor (D₂R) is a GPCR and an important drug target for schizophrenia treatment. Here, the authors present the crystal structure of human D₂R in complex with the antipsychotic drug spiperone, which is of interest for designing antipsychotics with improved receptor selectivity.

By combining genome-wide clustered regularly interspaced short palindromic repeats with Cas9 screening and cryo-electron microscopy structure analysis, the authors identified transmembrane protein 63B as a lipid scramblase that detects structural changes in the lipid bilayer and scrambles lipids to regulate membrane lipid distributions.

Carbon fibre is a lightweight next-generation material with various applications, but its production often requires expensive and toxic organic solvents, as well as highly energy-intensive heating processes. Here, the authors describe the polymerisation and spinning of carbon fibre using water, along with the implementation of a rapid heating process to reduce energy consumption.

In wildlife tagging, stress from capture and handling can alter post- release behavior and potentially study interpretations. This study of 42 mammal species shows that these effects diminish within 4–7 days, and quicker for animals in high human activity areas indicating adaptation to disturbance.

Here, Imamuraet al. conduct meta-analysis of genome-wide association studies to identify novel susceptibility loci for type 2 diabetes (T2D) in the Japanese population. By doing so, this study shows that both ethnicity-specific and ethnically-shared genetic loci can contribute to T2D risk.

New structures of copper containing proteins with cupredoxin-like folds confirm earlier predictions, and reveal electron-transfer routes in cytochrome oxidase, while a new fold for amine-oxidase reveals a new use for copper in forming self-derived quino-cofactor.

Determination of the crystal structure of the human A_2A adenosine receptor in complex with an inverse-agonist antibody shows that the allosteric site of the receptor inhibits agonist binding and that the antibody locks the receptor in an inactive conformation.

Previous studies identified an association between the 2q35 locus and breast cancer. Here, the authors show that a SNP at 2q35, rs4442975, is associated with oestrogen receptor positive disease and suggest that this effect is mediated through the downregulation of a known breast cancer gene, IGFBP5.