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Membrane ion channels can be responsive to a variety of stimuli such as pressure, temperature, or pH. Here, the authors show that simply shining 365 nm light activates a native potassium channel in rodent pain-sensing neurons, delivering powerful analgesia without drugs or genetic manipulations.

Viral proteins can achieve high multifunctionality, but mechanisms are poorly understood. This study shows structural flexibility of rabies virus P protein enables RNA binding and phase separation to expand functions by infiltrating host condensates.

Specific pain-sensing nociceptors and chemosensory tuft cells form a circuit to promote type 2 immune responses in the intestine.

UCN2 acts as a ligand for the GPCR CRHR2 and there have been conflicting reports on whether UCN2 treatment improves or worsens glucose tolerance. Here, the authors show that acute UCN2 recruits Gs and decreases glucose uptake, while chronic treatment desensitizes CRHR2 and improves glucose uptake.

Dietary n-6 PUFAs enhance adipose tissue expandability through the PPARγ–LPCAT3 membrane remodelling axis.

DNA affinity purification and sequencing (DAP-seq) allows genome-scale studies of transcription factor (TF)-binding sites with high reproducibility. Here, Lax et al. use this technique to characterize 58 TFs encoded by genes regulated by adenine methylation, and provide insights into the regulatory mechanisms of gene expression in an opportunistic pathogenic fungus.

This study examined the impacts of drought on future global staple crop production and how drought and socio-economic factors may impact individual countries’ food security. Although drought has a small impact on global mean production, some countries may face drought-related production losses exceeding 20%.

VRACs are ubiquitously expressed osmosensitive ion channels assembled from LRRC8A-E subunits. Here, the authors determine the structures of a LRRC8A:D VRAC using cryo-EM and identified that these channels are gated by lipids inside the channel pore.

Distinct cytochrome P450 (CYP) activities associated with specific CYP-redox partnerships show that divergent enzyme activities between human hepatocytes and microsomes may be driven by a mismatch in redox-partner interactions.

Affinity-proteomics platforms often yield poorly correlated measurements. Here, the authors show that protein-altering variants drive a portion of inter-platform inconsistency and that accounting for genetic variants can improve concordance of protein measures and phenotypic associations across ancestries.

Perivascular and leptomeningeal macrophages, collectively termed here parenchymal border macrophages, are shown to regulate flow dynamics of cerebrospinal fluid, implicating this cell population as new therapeutic targets in neurological diseases such as Alzheimer’s.

Azacitidine (AZA) response in myelodysplastic neoplasms is unpredictable. Here, the authors show in a phase 2 trial that while global methylation changes did not differ by response, baseline and initial CpG methylation differences in HSPCs predicted AZA response.

Analysis of medulloblastomas in humans and mice shows that the functional consequences of ZIC1 mutations are exquisitely dependent on the cells of origin that give rise to different subgroups of medulloblastoma.

Colorectal cancer is often diagnosed at later stages, leading to poor prognosis. Here, the authors utilise analysis of rectal mucus specimens using host and microbial analysis to detect cancer lesions.

Using a season-long field manipulation with an established model fish system on the Great Barrier Reef, this study demonstrates that limiting motorboat activity on reefs leads to faster growth and survival of more fish offspring compared to reefs experiencing busy motorboat traffic. Noise mitigation and abatement could therefore present a valuable opportunity for enhancing ecosystem resilience.

A 50 microRNA-based dynamic risk score for stratifying individuals with and without type 1 diabetes was developed using samples obtained from multicenter and multiethnic cohorts.

Morphological subtypes of autism spectrum disorder (ASD) may differ in their genetic bases. Chan et al. develop a method for calculating a patient-level, genome-wide rare variant score and find significant differences in rare and common variant associations between dysmorphic and nondysmorphic ASD groups.

The oomycete Phytophthora infestans is a damaging crop pathogen. Here, the authors show that a group of P. infestans secreted enzymes play roles in penetration and colonization of host plants by oxidising fragments of the polysaccharide pectin in the plant cell wall.

Sick heart and vessels skew hematopoiesis toward inflammatory myeloid cells. Rhode et al. show that hypertension, atherosclerosis and myocardial infarction cause endothelial dysfunction in bone marrow (BM), which in return causes overproduction of inflammatory myeloid cells and systemic leukocytosis in mice. This process is mediated by VEGF signaling, IL-6 and versican production by the BM endothelium.

The order in which driver mutations of colorectal cancer occur in intestinal epithelium can determine whether clones are positively or negatively selected and can shape subsequent tumour development.

García-Prat, Perdiguero, Alonso-Martín et al. show that skeletal muscle contains a subpopulation of quiescent stem cells, maintained by FoxO signalling, that is preserved into late life but declines in advanced geriatric age.

A recombinant antivenom composed of eight nanobodies provides broad protection against venom-induced lethality and dermonecrosis in mice challenged with venoms from cobras, mambas and rinkhals snakes.

Zinc finger protein transcription factors are developed for the selective silencing of the mutant huntingtin gene in human neurons in vitro and multiple animal models of Huntington’s disease in vivo while preserving expression of the wild-type allele.

The heterochromatic 'condensates' may not be conserved across mammals. This study highlights the influence of host genome on nuclear architecture and challenges the hypothesis that heterochromatin and MeCP2 undergo phase separation.

Metastatic cells can mimic many of the phenotypic behaviors of embryonic cells. Here, the authors generate a melanoblast-specific transcriptome using a genetically engineered mouse model and identify KDELR3 as a pro-metastasis gene in melanoma.

Brain microvascular dysfunction occurs in Alzheimer’s disease and other taupathies. Here the authors show that soluble pathogenic tau accumulates in brain microvascular endothelial cells of P301S(PS19) mice modeling tauopathy, and that it contributes to vascular deficits in these mice.

CD40 is typically understood as a costimulatory molecule. Here, the authors show CD4⁺ T cell-induced CD40 signaling in conventional type 1 dendritic cells results in complicated gene expression that can enhance CD8⁺ T cell priming by various underappreciated and independent mechanisms.

Black and white fonio are two small indigenous grain cereals grown in West Africa. Here, the authors reveal their independent domestication and cultivation histories through population genetics and demographic history analyses.

The transcription factor NFIL3 acts antagonistically to C/EBP proteins by binding the Zeb2 enhancer to prevent Zeb2 expression and the development of the conventional type 2 dendritic cell lineage.

Analysing whole-genome sequences from 68 rattlesnakes, the authors show a role of long-term balancing selection in maintaining diversity of multiple venom gene families and find reduced selective interference of venom genes with neighbouring loci.

Myelofibrosis causes a pathological remodelling of the bone marrow, which becomes stiffer and more elastic, thus promoting the proliferation of proinflammatory monocytes and their differentiation into dendritic cells.

Coronary heart disease is the leading cause of death worldwide with multiple environmental and genetic risk factors. Here the authors integrate genomic, epigenomic and transcriptomic mapping to elucidate causal variation and mechanisms of known genetic associations.

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.

By constructing an evolutionary trajectory of the cyclostome-gnathostome Pou5 gene family and comparing the structural and phenotypic protein variations, the authors uncover the origin of functional characteristics for the pluripotency factor Oct4.

Kallies and colleagues examine the role of the chromatin regulator SATB1 in CD8⁺ T cell differentiation during viral infection and cancer. They show that SATB1 is a negative regulator of exhausted CD8⁺ T cell expansion and effector differentiation.

Here, the authors characterize the epigenetic landscape of the human fungal pathogen Rhizopus microsporus with a focus on symmetric DNA N6-methyladenine, revealing its regulatory role in gene expression and its essentiality for viability.

Examination of the sulfur and copper contents of global cratonic peridotites combined with new high-pressure experiments shows that the migration of carbonated melts towards cratonic margins explains the co-location of magmatic metal deposits with carbonatites.

Comprehensive genomic profiling of human H3K27M mutant diffuse midline gliomas, combining single-cell RNA sequencing and ATAC sequencing with bulk ChIP sequencing and other data, proposes distinct oligodendrocyte populations as potential cells of origin.

In mass photometry, the optical contrast generated by individual molecules at a glass–water interface enables mass-resolved quantification of biomolecular mixtures. This protocol describes how to optimize and validate this method.

Atherosclerosis results from the accumulation of lipoproteins in the vascular wall. Here, Thierer et al. report the design of a chemiluminescent reporter for atherogenic lipoproteins using fusion of apolipoprotein-B to a luciferase enzyme, and find it bears potential for the identification of regulators of lipoprotein metabolism in vivo.

Amyloid-like proteins are central to age-related diseases, such as Alzheimer’s and Parkinson’s. Here, the authors show that transcription errors can produce mutant proteins with enhanced amyloid- and prion-like properties in human cells.

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.

Compound freeze-dry events have been the primary drivers of historical yield loss in the south of Northern China, whereas compound hot-dry events  have dominated in other regions. Statistical analyses and climate simulations indicate that these compound extremes are projected to intensify under future climate scenarios.

Severe COVID-19 is characterized by an accumulation of and functional changes in neutrophils. Using metabolomics, the authors demonstrate that neutrophils display a reduction in GAPDH activity in severe COVID-19 and that GAPDH inhibition promotes neutrophil extracellular trap formation.

Partitioning of FtsN and the septal peptidoglycan synthesis complex between an active synthesis track and an inactive denuded glycan track coordinates opposing peptidoglycan synthesis and degradation activities in E. coli.

PU.1 is a master regulator of myeloid development but its role in disease-relevant neutrophils is not well known. Here, the authors look at primary neutrophils from a human population and find that genetic variants affecting binding of PU.1 are associated with cell count and disease susceptibility.

Callahan et al. show that GC and extra-GC sites spawn distinct MBC subsets. MBC precursors have open chromatin regions (OCRs) that will remain open in MBC progeny, with extra-GC and GC-derived MBCs having distinct OCRs and functions.

Synapse-tuned CAR immune cells effectively kill solid tumor cells.

Cancers of the same tissue type are characterized with different molecular features depending on anatomical location. Here, the authors show that proximal and distal colon stem cells have distinct transcriptional programs mediated by the transcription factor CDX2, with differential roles in colon cancers based on anatomical location.