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A human neural organoid cell atlas integrating 36 single-cell transcriptomic datasets shows cell types and states and estimates transcriptomic similarity between primary and organoid counterparts, showing potential to assess organoid fidelity and facilitate protocol development.

Whole-genome sequencing analysis of 81 prehistoric individuals reveals how the genetic makeup of people from the North Pontic region was influenced by waves of migration during the Eneolithic period and Early Bronze Age.

Birdshot chorioretinopathy is an inflammatory eye condition strongly associated with HLA-A29. Here the authors use a single cell RNA sequencing approach to characterise NK cell involvement in this disease and show that CD8^bright CD244^bright NK cells are associated with active disease.

This study identifies candidate safeguard repressor transcription factors that repress alternate lineages in mature cell types and provides functional evidence that Prox1 performs such a function in hepatocytes during reprogramming, regeneration and in cancer.

Overexpression of c-MYC regulates tumor metabolism in pancreatic ductal adenocarcinoma (PDAC). Here the authors identify ELOVL6, a fatty acid elongase regulated by c-MYC, as a potential therapeutic target of PDAC.

A genome-wide association study meta-analysis combined with multiomics data of osteoarthritis identifies 700 effector genes as well as biological processes with a convergent involvement of multiple effector genes; 10% of these genes express the target of approved drugs.

High-energy interlayer excitons in van der Waals semiconducting transition metal dichalcogenides lie far above the bandgap and emit in the ultraviolet range.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

ATP production by mitochondria requires the efficient flow of protons through the F₁F_O ATP-synthase complex. Jonas and colleagues show that Bcl-xL interacts with the F₁F_O complex in the mitochondrial matrix and increases the efficiency of this enzyme by decreasing proton leak.

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.

Analysis of gravitational waves from merging binary neutron stars was accelerated using machine learning, enabling full low-latency parameter estimation and enhancing the potential for multi-messenger observations.

Evidence for a past large explosive eruption within the Santorini caldera suggests that early stages of silicic caldera cycles can be more hazardous than previously assumed, according to analyses of intra-caldera deposits from the Kameni Volcano.

Understanding the underlying pathophysiology of obesity can help prevent this condition. Here, the authors perform a GWAS of BMI in diverse ancestries, finding four missense variants in FRS3 that affect BMI.

Photoemission experiments demonstrate that the photon number statistics of the exciting light can be imprinted on the emitted electrons, allowing the controlled generation of classical or non-classical electron number statistics of free electrons.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

The study reveals the cryo-EM structure of human MICAL1, an enzyme that depolymerizes F-actin. Structural analyses show a conserved autoinhibition mechanism through intramolecular interactions between the N-terminal and C-terminal domains.

Many natural products are produced by non-ribosomal peptide synthetases in an assembly-line fashion. How these molecular machines orchestrate the biochemical sequences has remained elusive. It is now understood that an extended-conformation ensemble is needed to coordinate chemical-transformation steps whereas the biosynthesis directionality is driven by the enzyme’s innate conformational free energies.

Hibernating brown bears maintain their muscle mass, which is due to a drastic reduction in metabolic rate. Here, De Napoli et al. show that this is partly due to a reduction of energy consumption by the motor protein myosin in resting skeletal muscle that increases the super relaxed state stability.

Modified vaccinia Ankara (MVA) virus is the vaccine deployed to curb mpox. Here the authors conduct a multiplexed proteomic analysis to quantify cellular and viral proteins throughout MVA virus infection of human fibroblasts and macrophages and see substantial remodelling of the host proteome.

Genome-wide association analyses comprising 14,256 cases and 1,199,156 controls and incorporating correlated cardiac magnetic resonance imaging traits provide insights into the molecular etiology of dilated cardiomyopathy.

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.

Frameshift mutations that create arginine-rich basic tails in transcription factors and other proteins can lead to altered phase separation in the nucleolus, which in turn leads to syndromes such as brachyphalangy, polydactyly and tibial aplasia.

Although irrigation expansion during the 20th century masked or even reversed local warming trends over some intensely irrigated regions, the exposure to moist-heat extremes of local population has increased due to higher air humidity.

A high proportion of confirmed SARS-CoV-2 cases in Denmark were sequenced during the pandemic and linked to demographic, spatial and temporal data. Here, the authors analyse 290,000 genomes sampled in 2021 to demonstrate the value of this high coverage, detailed data set.

The molecular and cellular causes of glaucoma are not well understood. Here, the authors integrate GWAS with genetic regulation and single cell expression from multiple eye tissues to identify genes and key cell types that affect glaucoma pathogenesis.

A proof-of-principle study reports a complete photonic quantum computer architecture that can, once appropriate component performance is achieved, deliver a universal and fault-tolerant quantum computer.

Non covalent complexes are often considerably destabilized in the solvent. Here the authors combine vibrational Raman and NMR spectroscopy with a coupled-cluster computational investigation to show that the solvent polarity enhance the complex stability of a Me₃NBH₃ complex.

MS-based immunopeptidomics provides direct evidence for HLA peptide-antigen presentation, which is indispensable for therapeutic use. Here the authors present an ion mobility MS-based immunopeptidome workflow, largely expand benign reference databases and enables next generation tumor antigen discovery.

A tunable quantum dot device in Bernal bilayer graphene possesses a spin–valley relaxation time of 38 s at millikelvin temperatures.

Protein-tag degree of labeling (ProDOL) is a versatile reference-based approach for experimentally determining the degree of target labeling for improved protein counting and quantification and for optimizing labeling protocols in fixed and live cells.

Vaccination in glioblastomas does lead to the emergence of tumour-antigen-specific T cells but T cell dysfunction, poor tumour infiltration and persistence hinder efficient tumour killing. Here authors identify a T cell receptor in a vaccinated glioblastoma patient that specifically recognizes the glioblastoma stem cell antigen PTPRZ1 and utilise it in T cell receptor-engineered T (TCR-T) cell therapy, resulting in efficient tumour cell killing in vitro and in a mouse model.

Few studies have suggested that enteric glial cells (EGCs) promote colorectal cancer growth. Here the authors show that EGC-derived IL-6 promotes the expansion of tumorigenic SPP1⁺ tumor-associated macrophages, associated with worse disease outcome.

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.

Across 27 countries, Većkalov and Geiger et al. find that scientific consensus messaging on climate change is an effective, non-polarizing tool for changing misperceptions, beliefs and worry but not support for public action.

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.

Formation of urate and calcium pyrophosphate micro-crystals is responsible for painful inflammatory flares in gout and chondrocalcinosis. Here the authors show that the osmo-sensitive LRRC8 anion channel is involved with macrophage inflammasome activation by crystals involving cell volume regulation and ATP release leading to P2Y receptor activation.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

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.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

Drugs targeting cardiovascular disease (CVD) can have negative consequences for liver function. Here, the authors combine genome wide analyses on 69,479 individuals to identify loss-of-function variants with beneficial effects on CVD-related traits without negative impacts on liver function.

Pyroptosis has been implicated in many diseases with aberrant inflammation. Here, Kopp et al. characterize single-chain nanobodies targeting the human gasdermin D protein as tools to inhibit pyroptosis.

Medulloblastoma in children is a difficult cancer to treat and the immune response to this tumour is not fully understood. Here the authors characterise and validate T cell epitopes from these cancers using an immunopeptidomics approach, comparing different molecular subtypes.

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.

Magnetic atomic chains assembled on the surface of superconductors are a potential platform for engineering topological superconducting phases. Here the authors step towards this by manipulating magnetic atoms at interstitial sites to tune interatomic interactions and control the Yu-Shiba-Rusinov states that form.

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.