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Wearable data from 7,013 participants in the All of Us Research Program show that park accessibility across 53 US cities is positively associated with daily step counts, providing a mechanism for how urban green space can improve health.

Here the authors reveal how replication stress in BRCA2-deficient cells triggers a mutagenic cycle of APOBEC3B upregulation, uracil accumulation at stalled forks, and DNA damage, uncovering a self-reinforcing loop that fuels genomic instability.

Here Jaster et al., show a single psilocybin dose produce sex-specific post-acute changes in opioid reward and withdrawal via 5-HT2A receptors in frontal cortex-to–nucleus accumbens circuits, with epigenetic and synaptic changes shaping therapeutic potential.

Meiosis is a cell division program that produces haploid gametes and is initiated by a retinoic acid-dependent process. Here the authors report that a meiosis-specific protein, MEIOC, is upregulated in a retinoic acid-independent manner and is required to stabilise meiosis-specific transcripts.

In this study, the authors assess the global response to the toxic aldehyde glyoxal (GO) in Pseudomonas aeruginosa, suggesting that GO controls quorum sensing during infection through a mechanism involving a novel protein, ArqI.

Notch1 mutations have opposing effects on clonal growth in normal and tumor cells of the mouse esophagus. In a mouse model of squamous esophageal tumorigenesis, Notch1 blockade reduced premalignant tumor growth, suggesting that it might be an effective prevention strategy for the disease.

Epithelioids are genetically stable, self-sustaining three-dimensional cultures. They may be used to investigate various aspects of epithelial biology over several months without need for passaging. In this paper, mouse epithelioids are used to identify drivers of clonal expansion in the esophagus.

TRIM7 acts as an antiviral factor during SARS-CoV-2 infection, by ubiquitinating the M protein on K14 and inhibiting caspase-6-dependent apoptosis. The natural K14 mutations in circulating strains support the physiological role of M ubiquitination.

Zhang et al. provide evidence that, during meiosis, recombination proteins assemble into active droplets, the coarsening of which partially explains the phenomenon of crossover interference.

Amyloid fibrils can adopt a range of distinct conformations, yet it is challenging to rapidly discriminate between these polymorphs. Now methods have been developed to screen large, diverse libraries of turn-on fluorescent dyes to rapidly identify probes that recognize fibril subsets.

A study uses single-molecule footprinting to measure protein occupancy at regulatory elements on individual molecules in human cells and describes how different properties of transcription factor binding contribute to gene expression.

Genome-wide analyses identify 30 independent loci associated with obsessive–compulsive disorder, highlighting genetic overlap with other psychiatric disorders and implicating putative effector genes and cell types contributing to its etiology.

In Drosophila, long noncoding RNAs (lncRNAs) are expressed most highly in male germline cells. Here the authors report the subcellular distributions of approximately 600 Drosophila lncRNAs in male reproductive tissues, indicating potential involvement in spermatogenesis, fertility and evolution.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

The authors use single-nucleus RNA-seq to identify 10 GABAergic interneuron subtypes in human cortex layer 1. Molecular, morphological, and physiological evidence points to an emerging human cell type, the rosehip cell, not found in other species.

Reducing the competitive advantage conferred by driver mutations can abrogate expansions of mutant clones in healthy tissue in mice. This suggests ways to prevent cancer and other diseases that are associated with somatic mutations in humans.

Ancient sulfate mineral compositions reflect an increase in Earth’s oxidation state ~400 million years ago, likely including an increase in atmospheric oxygen levels and shift in mineral weathering pathways.

The Omicron variant is partially attenuated, likely because it fails to efficiently infect lung cells. Here, Hoffmann et. al. show that this defect can be lost during Omicron evolution as demonstrated for the subvariant BA.5 that robustly infects lung cells in vitro and in vivo.

The hippocampus is a brain region critically involved in memory. In this study, the authors demonstrate that reactivating hippocampal neurons associated with positive memories can disrupt a fear response in mice.

RMC-7977, a compound that exhibits potent inhibition of the active states of mutant and wild-type KRAS, NRAS and HRAS variants has a strong anti-tumour effect on RAS-addicted tumours and is well tolerated in preclinical models.

The authors show that the assembly of the meiotic chromosome axis in worms depends on activation of the master DNA-damage response kinase ATM, which leads to destabilization of the cohesin-unloader WAPL. Similar ATM-dependent WAPL inhibition also occurs in cohesin-rich genomic regions upon DNA-damage induction.

Glioblastoma is an immunologically cold tumour, with poor CD8 + T cell infiltration and enrichment in immunosuppressive tumour-associated myeloid cells. Here, the authors generate a bispecific lipid nanoparticle targeting CD47 and PD-L1, combined with a STING agonist, to promote anti-tumour immunity.

Hyper-phosphorylated tau accumulates in Alzheimer’s disease; but the roles of these phosphorylation sites are unclear. Here the authors show that phosphorylation of a single site, pSer416, limits its turnover and promotes accumulation.

Studies in mice show that observational fear learning is encoded by neurons in the dorsomedial prefrontal cortex in a manner that is distinct from the encoding of fear learned by direct experience.

In this immunological ancillary study of the PREVAC trial, the authors show that approved Ebola virus vaccines induce memory T-cell responses that persist during the five year follow-up after initial vaccination.

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).

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Pairing centres are specialized regions on worm chromosomes that mediate homologous pairing during meiosis. Sequence motifs that recruit proteins involved in pairing have been identified and they are sufficient for chromosome synapsis and segregation during meiosis.

Tumor cell in the peritoneum are often exposed to shear forces generated by ascitic flow during metastasis. Here, the authors show that metastatic cancer stem cells tether more and roll slower than the non-metastatic counterparts, and that sialyl-Lewis^x -P-selectin axis mediates peritoneal metastasis.

Design of a bivalent inhibitor containing an ATP-competitive moiety and rapamycin-modified FRB binding ligand that selectively inhibits mTORC1 results in potent and durable inhibition of 4EBP1 phosphorylation and cell proliferation in vitro and in vivo.

Overexpression of human antigen R (HuR) correlates with high grade tumours and poor patient prognosis. Here, the authors engineer a TRIM21 biological PROTAC to demonstrate the benefit of a targeted protein degradation approach to deplete HuR, resulting in tumour growth inhibition in pre-clinical cancer models by altering the HuR-regulated proteome.

Carbonate melt is one of the most important materials involved in the carbon cycle of the Earth’s interior; however, its mobility is poorly understood. Here, the authors suggest that carbonate melts possess much lower viscosities than previously thought, which in turn suggest very high mobility.

An ensemble of simulations indicates that ongoing climate change will exceed the bounds of historical climate variability some time in the mid to late twenty-first century and that the burden of rapid climate adaption will occur earliest in highly biodiverse and often economically challenged tropical areas.

In this study, the anti-anginal drug ranolazine is found to sensitize BRAF inhibitor-resistant melanoma to targeted therapy and immunotherapy by rewiring fatty acid oxidation and the methionine salvage pathway.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Reninomas are very rare kidney tumours of juxtaglomerular cells. Here, the authors analyse reninomas using whole-genome and transcriptome sequencing, and reveal the presence and functional effects of NOTCH1 rearrangements.

A photoswitchable analog of spingosine-1-phosphate (S1P) that allows for modulation of the action of this bioactive lipid exhibits prolonged metabolic stability compared to S1P, activates S1P receptors in cells and mediates nociception in mice.

The development of split-engineered base editors (seBEs) enables small-molecule control over DNA deaminase activity, decreasing off-target effects and offering a generalizable solution for temporal control over precise genome editing.

Loss of surface CD19 expression by leukemic cells leads to resistance and relapse to CD19-targeted CAR-T therapies. Here the authors show that loss of SPPL3 in malignant B cells results in hyperglycosylation of CD19.

A nematode symbiont Robbea hypermnestra divides longitudinally and asynchronously in a host-oriented fashion.

Roberti, Grier et al., assessed metabolic and lipid profiles in pediatric type 1 diabetes patients at diagnosis and post-insulin treatment, utilizing UHPLC-MS/MS methods. Findings reveal significant associations between acyl-carnitines, ketoacidosis, and hematological changes, suggesting potential biomarkers and therapeutic targets.

Existing methods for generating sgRNA predictions do not account for the tracrRNA sequence. Here the authors report an on-target model, Rule Set 3, to generate optimal predictions for multiple tracrRNA variants, and validate this on a new dataset of sgRNAs showing improvement over prior prediction models.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.