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Cancer cells can depend on Pol θ for survival. Here, the authors show that Pol θ typically initiates end-joining at microhomologies that contain mismatches, without requiring bidirectional synthesis. This suggests a revision of the definition of microhomology for analysis of genomic mutations.

Here, the authors show that post-translational molecular signatures of human skeletal muscle in response to acute or chronic aerobic and resistance exercise are distinct, potentially dictating the differential physiologic adaptations to different exercise modes.

The role of nicotinic acetylcholine receptors in human cortical development remains largely unexplored. Here authors investigate CHRNA7 and CHRFAM7A, uncovering their involvement in radial glial cell proliferation and neuronal differentiation, and identify YAP1 as a downstream effector of cholinergic signaling.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Here, the authors show that delafloxacin, a respiratory antibacterial fluoroquinolone, binds the Streptococcus pneumoniae topoisomerase IV-DNA cleavage complex in a distinct tilted-ring conformation involving multiple Mg^2 + , K⁺ and water links. Intrinsic target affinity likely contributes to activity against quinolone-resistant bacteria.

Whether multimorbidity accelerates brain Aβ deposition in humans remains largely unknown. Here, the authors demonstrate that higher self-reported multimorbidity burden predicts increased brain Aβ accumulation rates in the ADNI cohort.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Previous work has shown that electronic and structural transitions in VO₂ can be decoupled by realizing an electronic transition within a monoclinic phase. Here, the authors extend this to the rutile phase by demonstrating a photodoping-driven transition from an insulating to a metallic rutile phase.

The morphogenetic events that occur during gastrulation involve dramatic cell- and tissue-level changes. Here they show that propagation of nematic order, leading to long-range spatial correlation, is universally conserved during metazoan embryogenesis.

This study uncovered genetic associations with environmental sensitivity in psychiatric and neurodevelopmental traits in an international collaboration using data from more than 21,000 monozygotic twins—the largest genetic study of monozygotic twin differences to date.

Operation of lithium–sulphur batteries suffers from uncontrolled lithium polysulphide formation and corrosion at the anode. Huang et al.design an integrated anode structure composed of electrically connected graphite and lithium metal, which alleviates the problems and leads to high battery performance.

Protein citrullination regulates the physiological function of proteins and is linked to various autoimmune disorders. Here, the authors report on the allosteric targeting of PAD1-4 leading to broad inhibition of protein citrullination in neutrophils.

A comprehensive analysis of the cell-specific molecular regulatory mechanisms underlying post-traumatic stress disorder in the human prefrontal cortex.

Stadler et al. evaluate the diagnostic value of urinary tract infection biomarker, nitrite, in predicting disease progression and treatment efficacy. The longitudinal measurement of nitrite in an in-vitro UTI distinguishes between amoxicillin-resistant and susceptible E. coli strains and correlates with bacterial colony-forming unit counts in-vitro and in clinical UTI.

Riebesell et al. introduce Matbench Discovery, a framework to compare machine learning models used to identify stable crystals. Out of several architectures, they find that universal interatomic potentials perform best in the competition.

Poly(carboxybetaine) lipids enhance mRNA lipid nanoparticles efficacy and reduce their immunogenicity, being promising alternatives to poly(ethylene) glycol lipids used in traditional mRNA lipid nanoparticle formulations.

Materials with variable and reversible thermal conductivities are important in technologies, and yet such materials are rare. Here, Cho et al. report in situmeasurements of thermal conductivity of lithium cobalt oxide, and show how to reversibly modulate thermal conductivities over a considerable range.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

¹³⁴Ce and ¹³⁴La have great potential as companion diagnostic isotopes for radiotherapeutics labelled with α-emitting ²²⁵Ac and ²²⁷Th. Now, by controlling the Ce^III/Ce^IV redox couple, the large-scale production, purification and characterization of ¹³⁴Ce- and ¹³⁴La-based radiolabels has been achieved and their use for in vivo positron emission tomography is demonstrated.

Constitutional mismatch repair deficiency (CMMRD) is associated with high cancer incidence early in life. Here, the authors perform a genomic analysis of CMMRD-associated tumors and find mutational patterns influenced by the affected mismatch repair gene, tumour type, and treatment history.

The development of efficient actuators and the understanding of their mechanisms is crucial for improving their application. Here, the authors develop a self-standing film of an ionic covalent organic framework which undergoes a reversible photoactuation following a triple energy conversion cascade in a short time.

From modern seasonal to the deep time, global data show that continental hydrology has a direct and consistent effect on river and marine Li isotope compositions, highlighting a crucial role of climate on Earth’s weathering and the carbon cycle.

Trees come in all shapes and size, but what drives this incredible variation in tree form remains poorly understood. Using a global dataset, the authors show that a combination of climate, competition, disturbance and evolutionary history shape the crown architecture of the world’s trees and thereby constrain the 3D structure of woody ecosystems.

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

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.

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.

Isotope production is usually associated with nuclear reactors, but there are alternative approaches. One such proposal is based on the well-known atomic physics experimental techniques of optical pumping and magnetic guiding, and its viability for isotope separation is now experimentally demonstrated.

PCSK9 regulates low density lipoprotein-cholesterol import and determines organ preference of metastatic pancreatic ductal adenocarcinoma, with PCSK9-low cells metastasizing to the liver and PCSK9-high cells preferring the lung.

The upsurge of mpox has stimulated the development of new vaccines and therapeutics. Here, the authors describe a VLP vaccine comprised of modified MPXV proteins M1, A35, and B6 and demonstrate induction of protective antibodies in mice and non-human primates.

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.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Checkpoint inhibitor (CPI) therapy is modestly effective in Glioblastoma patients, with some patients not benefitting at all. Authors here present the outcomes of single arm prospective clinical trial employing combination CPI therapy in newly diagnosed GBM and identify the pre-treatment genetic, microbiome and immunological factors that might contribute to sensitivity.

Parasitic reactions between Li metal and electrolytes need to be mitigated in Li-metal batteries. Here, the authors report the use of a fluorinated orthoformate-based electrolyte, leading to a monolithic solid–electrolyte interphase and subsequently a high-performance Li-metal battery.

Sialoglycan receptor binding promotes the D2 ___domain up conformation in the HKU1 coronavirus spike protein. Here the authors show that this conformational change is driven fundamentally by the full structuring of the canonical embecovirus binding site.

Colour code on a superconducting qubit quantum processor is demonstrated, reporting above-breakeven performance and logical error scaling with increased code size by a factor of 1.56 moving from distance-3 to distance-5 code.

Lithium metal is an ideal anode material for rechargeable batteries, but lithium dendritic growth and limited Columbic efficiency prevent its applications. Here, the authors report the use of highly concentrated electrolytes composed of ether solvents and the salt lithium bis(fluorosulfonyl)imide to enable high-rate cycling of lithium anode.

Reflection interference microscopy provides dynamic, non-invasive, operando imaging capabilities that enable the solid–electrolyte interphase formation and evolution of a battery to be mapped in real time with high sensitivity.

In this study authors use morphological profiling and CRISPR/Cas9 genetic screens to investigate the mechanisms by which BiDACs induce the degradation of plasma membrane receptor tyrosine kinases (RTKs) EGFR and Her2.

Sulfur encapsulation with nanoporous carbon is a widely adopted approach for Li–S batteries, but this often results in low sulfur utilization and low volumetric energy density. Here the authors report a non-encapsulation approach for the growth of S-containing species with low-surface-area carbon and high energy.

Myostatin and activin A are the two primary negative regulators of muscle mass. Blocking these circulating ligands during GLP-1 therapy induces improved body composition through preservation of lean mass and enhanced fat mass loss in obese primates.

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.

Natural ecosystems efficiently sequester CO₂, but containing and controlling living systems remains challenging. Here, the authors engineer a photosynthetic living material for dual CO₂ sequestration via biomass accumulation and microbially-induced calcium carbonate precipitation.

This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the molecular basis of human disease.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

The polyoxoanion [P₂W₁₈O₆₂]⁶⁻ has been shown to reversibly accept up to 18 electrons upon reduction in aqueous solution. The resulting highly reduced solution can then be used either for the on-demand generation of hydrogen over a catalyst bed, or as a high-energy-density electrolyte in a redox flow battery.

The development of Li metal batteries requires understanding of cell-level electrochemical processes. Here the authors investigate the interplay between electrode thickness, electrolyte depletion and solid–electrolyte interphase in practical pouch cells and demonstrate the construction of high-energy long-cycle Li metal batteries.