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Activation of G_s signaling at mitochondria by mitoDREADD-G_s increases mitochondrial metabolism, leading to better memory in mouse models of dementia, directly linking brain mitochondrial deficits to cognitive symptoms of neurodegenerative diseases.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

DNA double strand breaks (DSBs) are among the most deleterious types of damage and there is strong evidence indicating a relationship between breaks and transcription. Here the authors provide a high-resolution, genome-wide map of induced DSBs and observe ATM-dependent transcriptional repression.

Photosynthetic organisms, fungi, and animals contain distinct pathways for vitamin C biosynthesis, but the final biosynthetic step consistently involves an oxidation reaction catalysed by the aldonolactone oxidoreductases. Here, the authors investigate the origin and evolution of the diversified activities and substrate preferences featured by these enzymes using different methods and find evidence that they share a common ancestor.

Digital trace data from search engines lacks information about the experiences of the individuals generating the data. Here the authors link search data and human computation to build a tracking model of influenza-like illness.

Materials that demonstrate long-range magnetic order are synonymous with information storage. Here, the authors report the effect of pressure on two mononuclear rhenium compounds that exhibit long-range magnetic order under ambient conditions via a spin canting mechanism, whereT_cis proportional to pressure.

Eddy-covariance observations suggest that rain pulses over global drylands drive substantial soil carbon emissions, which are underestimated in current measurement and modelling approaches.

X-chromosome inactivation (XCI) contributes to sex bias in T cell immunity, but data on profiling XCI during human T cell development is still lacking. Here, the authors leverage allele-specific expression, sex-biased gene expression and DNA methylation data on human pediatric thymocytes to find surprisingly stable XCI during thymocyte differentiation.

An ecological footprint approach demonstrates that EU-27 residents demand more from nature than the region’s ecosystems can regenerate, with a quarter of biocapacity for food originating outside of the region.

Here the authors used cryogenic electron microscopy and biochemistry to understand how yeast Mcm10 exerts its essential role in DNA replication initiation, finding that it splits the double Cdc45-MCM-GINS-Polε structure. The lagging-strand template is ejected from each MCM ring as the central channel of the helicase becomes too tight to accommodate two DNA strands.

Stochastic nucleation prevents the repeatable multi-level response of phase change materials in integrated photonics. Here the authors circumvent this issue with a method using deterministic amorphization via spatially controlled microheater hotspots.

The antisense oligonucleotide rugonersen has acceptable safety and tolerability in children with Angelman syndrome and shows partial normalization of electroencephalogram abnormalities and clinical improvements relative to natural history.

Experiments and theory show how superlubricity can emerge in large flakes sliding on a surface when the lattices of the flake and the surface are incommensurate.

Detailed structures of yeast RNA polymerase III and its initiation complex shed light on how the transcription of essential non-coding RNAs begins and allow comparisons with other RNA polymerases.

Malaria chemoprevention is used for young children, but resistance mutations raise concerns on efficacy. In this analysis of trials across Africa, the authors show that prevention treatment protects >42 days against susceptible parasites but <12 days against highly resistant strains highlighting the importance of genomic surveillance for chemoprevention strategies.

Due to mechanical stress, hydropower systems can suffer severe fatigue damage during start-up. Here, the authors propose a machine learning procedure to identify start-up trajectories which minimize fatigue damage.

Here the authors report the cryo-EM structure of heart-derived fibrils of an AL amyloidosis patient. Surprisingly, the fibrils form helical superstructures with collagen VI, potentially signifying a distinct pathophysiological mechanism for amyloidoses.

Human-driven forest fragmentation could have major impacts on ecosystem functioning. This global analysis shows that the relationship between fragmentation and vegetation resilience in forests may differ depending on bioclimatic region and local environmental conditions.

Impairment at the neuromuscular junction (NMJ) is an early sign of ALS. Here, the authors show that the RNA-binding protein HuD causes NMJ and apoptosis phenotypes in human iPSC and Drosophila ALS models, highlighting a possible role in disease onset.

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.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

In their study, Dorman and Bendoumou et al., reveal a post-transcriptional regulation of unspliced HIV-1 RNA by host factors MATR3, MTR4, and the viral protein Rev, identifying a previously uncharacterized post-transcriptional block in nucleocytoplasmic export, which plays a crucial role in HIV-1 latency and reactivation.

The p140Cap adaptor protein is a tumour suppressor associated with improved prognosis in breast cancer. Here, the authors identify a role for p140Cap in preventing the immunosuppressive and pro-tumour function of polymorphonuclear myeloid-derived suppressor cells via downmodulation of the β-Catenin/Tumor Initiating Cells/G-CSF axi

Patients with cystic fibrosis are not reporting particularly sever outcomes upon SARS-CoV-2 infection. Here, the authors demonstrate decreased ACE2 levels is cystic fibrosis airway epithelia associated with impaired viral entry and replication.

Understanding molecular near neighbours is key for molecular optimization. Here, authors propose a transformer model that improves correlation between generation probability and molecular similarity, enhancing exploration of molecular neighbourhoods.

By characterizing APOB-reactive CD4⁺ T cells in patients with atherosclerosis, Roy et al. identify effector regulatory T (eT_reg) cells as the predominant autoreactive subset. These APOB-specific eT_reg cells are clonally expanded, express the plaque-homing receptor CXCR6 and progressively lose their regulatory phenotype as disease severity increases.

Dnmt3a mutations in mouse haematopoietic stem and progenitor cells equivalent to R882 mutations in human cause increased mitochondrial respiration, suggesting that this is a mechanism of clonal haematopoiesis and a potential therapeutic target.

Using survey and internet browsing data and expert ratings, Bhadani et al. find that incorporating partisan audience diversity into algorithmic rankings of news websites increases the trustworthiness of the sites they recommend and maintains relevance.

The BRCC36 isopeptidase complex (BRISC) is a deubiquitylase that stabilizes interferon receptors, driving inflammation. We discovered ‘BRISC molecular glue’ inhibitors (BLUEs) that selectively inactivate BRISC, promoting interferon receptor ubiquitylation and degradation to dampen immune responses.

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.

Ty3 retrotransposon integrates with an exquisite specificity upstream of RNA Polymerase III-transcribed genes, such as transfer RNAs. Here the authors resolve a cryo-EM structure of an active Ty3 intasome in complex with a TFIIIB-bound tRNA promoter, shedding light into the molecular determinants of harmless retrotransposition.

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.

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.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Islet transplantation for type 1 diabetes management is hindered by the life-long need for immunosuppressive medications. Here, the authors report an islet encapsulation device with local anti-rejection drug release that achieves long-term diabetes reversal in male rats and reduces drug-related toxicity.

Double Asteroid Redirection Test (DART) mission’s impact on asteroid Dimorphos has led to various impact related features. Here, the authors show that those features result naturally from the dynamical interaction of the ejecta with the binary system and solar radiation pressure.

Idiopathic pulmonary fibrosis is associated with increased abundance of Staphylococcus and Streptococcus in the lungs. Here, the authors identify a Staphylococcus nepalensis-derived peptide, named corisin, to induce apoptosis of lung epithelial cells and exacerbation of pulmonary fibrosis in mice.

Loss of Amplified in Liver Cancer 1 (ALC1) has been shown to confer PARP inhibitor hypersensitivity in BRCA-mutant cells. Here, the authors show that in ALC1-deficient BRCA-mutant cells, APE1 cleaves abasic sites at the forks resulting in DNA breaks and thereby enhances PARP inhibitor sensitivity.

Analysis using a combination of molecular and genetic epidemiological approaches reveals an interaction between female sex and the genetic variant PNPLA3 p.I148M that might explain why some women have increased susceptibility to fatty liver disease after onset of menopause.

PIP4Ks are phosphoinositide kinases often dysregulated in cancer. Here Poli and colleagues find that PIP4K2B is downregulated on soft substrates, and its depletion leads to altered nuclear mechanical properties and defects in cell spreading and motility.

Glutathione has pleiotropic functions in different organs. Here the authors specifically examine deletion of a glutathione synthetic enzyme in the liver of adult mice and show that lack of glutathione affects lipid abundance through repressing NRF2.

Macroglia are neural cells that have garnered less interest than neurons despite their crucial functions including neurogenesis. Here the authors use sequencing from several species to investigate the evolution of macroglia and of adult neurogenesis.

Time-resolved electron microscopy reveals the mechanism by which the origin recognition complex loads pairs of MCM helicases around DNA prior to bidirectional replication.

NK cells play an important role in anti-tumour immunity, however, the immune-hostile microenvironment often impairs their function. Here authors show that cancers disable autophagy in NK cells, and by restoring this process, intra-tumour NK cells could be re-invigorated.

Phenomena like imitation, herding and positive feedbacks in the complex financial markets characterize the emergence of endogenous instabilities, which however is still understudied. Here the authors show that the graph-based approach is helpful to timely recognize phases of increasing instability that can drive the system to a new market configuration.

This study shows how the yeast Ctf4 protein couples the DNA helicase, Cdc45–MCM–GINS, to DNA polymerase α — the GINS subunit of the helicase and the polymerase use a similar interaction to bind Ctf4, suggesting that, as Ctf4 is a trimer, two polymerases could be simultaneously coupled to a single helicase during lagging-strand synthesis.

The cell wall of the bacterial pathogen Group A Streptococcus is decorated with a polysaccharide termed GAC, which is a target for vaccine development. Here, Rush et al. characterize the linkage between GAC and peptidoglycan, and identify a protein that deacetylates the linkage and thus protects the pathogen against host cationic antimicrobial proteins.