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The M₅ muscarinic acetylcholine receptor represents a promising therapeutic target for neurological disorders. Here, the authors reveal a 2.1 Å cryo-EM structure of the M₅ bound to a selective positive allosteric modulator site that enables structure-based drug design.

Using ultrafast electron diffraction and deflectometry, the study tracks polarization and structural dynamics in NbOI₂ nanocrystals with femtosecond resolution, revealing coherent phonon generation and polarization enhancement after UV irradiation.

Microscopy drives biological discovery, yet high costs limit its access to resource-limited regions. We highlight examples of successful frugal microscopes that have overcome adoption barriers, offering a roadmap to expand affordable, quantitative imaging tools and foster impactful research in resource-limited settings.

A survey of sharks and rays on coral reefs within 66 marine protected areas across 36 countries showcases that the conservation benefits of full MPA protection to sharks almost double when accompanied by effective fisheries management.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

Discussions at a recent conference on microscopy technology dissemination spotlighted the importance of setting technology adoption capable of producing scientific outcome as the end goal. This Comment examines current global efforts in microscopy dissemination and summarizes the challenges and paths forward.

Fishing has had a profound impact on global reef shark populations, and the absence or presence of sharks is strongly correlated with national socio-economic conditions and reef governance.

From an analysis of participants in lipid-lowering trials for primary and secondary prevention of coronary artery disease, a polygenic risk score comprising 35 single nucleotide variants with predicted effects on endothelial cell function identified patients who benefited most from aggressive lipid-lowering therapy.

Stem cell migration plays critical roles in the regeneration of adult tissue. Here, the authors demonstrate that Wnt5a-mediated activation of non-canonical Wnt signaling promotes migration of airway stem cells after epithelial injury.

We may be discovering climate as it becomes less important to well-being. A range of technologies appears to have lessened the vulnerability of human societies to climate variation.

In humans, ADPKD can develop from “second hit” mutations in the PKD1 gene. Here, the authors show that human PKD1 contains guanine quadruplex structures that cause mutagenic double stranded breaks.

The role of ancestry in target discovery remains to be systematically explored. Here, the authors analyse data from 611 genome scale CRISPR/Cas9 viability experiments in human cell line models as part of The Cancer Dependency Map and identify ancestry-associated genetic dependencies.

Podosomes are actin structures important in multiple cell functions. Here, the authors use iPALM microscopy to reveal an “hourglass” shape of the podosome actin core, a protruding “knob” at the bottom of the core, and two actin networks extending from it.

Social inequalities may be reflected in how ecosystem services are distributed among groups of people. Here the authors estimate the distribution of three ecosystem services across demographic and socioeconomic groups in the US between 2020 and 2100, finding that non-white and lower-income groups disproportionately bear the loss of ecosystem service benefits.

The natural hallucinogen psilocybin — produced by so-called magic mushrooms — holds promise for the treatment of depression and other mental health conditions. Here, the authors provide a structural and biochemical analysis of the Psilocybe methyl transferase PsiM that provides mechanistic insight into the last step of psilocybin biosynthesis.

Variant detection in problematic genes is facilitated with a curated benchmark.

Trinucleotide-repeat-containing 18 (TNRC18), which has poorly understood functions, is now identified as an H3K9me3-specific reader that silences endogenous retroviruses.

Focal adhesions are dynamic structures that link the cell to the extracellular matrix. Here, the authors report that focal adhesions contain tropomyosin-decorated actin filaments, and show evidence that suggests specific functions in adhesion dynamics and cell migration.

A variant of MHC class I is protective against severe malaria disease and enriched in affected African populations. Here, Wroblewski et al., characterise the consequences of malaria infection in wild bonobo populations showing that the presence of malaria drives a similar evolution in immune genes.

The actin-based molecular motors, myosins, have also been linked to transcription, but their precise role has remained elusive. Here the authors show RNA polymerase II (RNAPII) is lost from chromatin upon myosin perturbation and that myosin acts as a molecular anchor to maintain RNAPII spatial organisation.

Here the authors present a deep learning framework for dementia diagnosis, which can identify persons with normal cognition, mild cognitive impairment, Alzheimer’s disease, and dementia due to other etiologies.

An autophagy receptor, NDP52, is recruited to the nucleus where it can bind DNA. The authors show this promotes changes in chromatin accessibility which supports transcription initiation, providing a direct link between autophagy and transcription regulation.

Bharathan et al. discover that the endoplasmic reticulum associates with keratin intermediate filaments and desmosomal cell–cell junctions, and that desmosomes and the keratin cytoskeleton regulate the distribution, dynamics and function of the endoplasmic reticulum network.

The plasma membrane can expand the blades of the PIEZO1 ion channel, impacting channel activation.

Garon and colleagues demonstrate that the association of HLA supertype B44 with response to immune checkpoint blockade in melanoma but not NSCLC is related to differential mutational features that influence HLA binding of neoepitopes.

Wheat yield is sensitive to temperature, but there could be substantial variation in this response across cultivars. Here the authors present data on the climatic responses of wheat cultivars in South Africa, highlighting which cultivars might be better able to maintain yield under warming.

An individual with multidrug-resistant HIV and Kaposi sarcoma achieved sustained viral suppression after treatment with an anti-CD4 domain 1 antibody and the injectable long-acting capsid inhibitor, lenacapavir.

A global dataset of the satellite-tracked movements of pelagic sharks and fishing fleets show that sharks—and, in particular, commercially important species—have limited spatial refuge from fishing effort.

A microfluidics-free, scalable single-cell RNA-sequencing method produces high-quality transcriptomes.

Pluripotent stem cell colonies are encircled by large cornerstone focal adhesions (FAs). Here, using super-resolution imaging, the authors describe features in the nanoscale makeup of these stable FAs such as inverted vinculin, lateral talin segregation and distinct kank protein distributions.

The genome is folded in 3-dimensions, though the lack of robust ultra-resolution imaging makes this difficult to visualise. Here, the authors present 3D-EMISH that combines serial block-face scanning electron microscopy with in situ hybridization.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

Observations from the JWST of the second brightest GRB ever detected, GRB 230307A, indicate that it belongs to the class of long-duration GRBs resulting from compact object mergers, with the decay of lanthanides powering the longlasting optical and infrared emission.

The hierarchy of symmetry breaking in magic-angle twisted bilayer graphene remains a topic of intense fundamental study. Here, the authors determine the spin polarization of symmetry-broken quantum Hall states and Chern insulators in MATBG using a twist-decoupled graphene probe.

This Perspective discusses strategies and challenges for the Molecular Phenotypes of Null Alleles in Cells (MorPhiC) Consortium as it aims to catalogue the molecular and cellular phenotypes associated with null alleles of all human genes.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Amyotrophic Lateral Sclerosis (ALS) is highly heritable but the mechanisms of sporadic ALS are not fully understood. In this study, the authors identify drivers of variation and disease-relevant changes in the epigenomic profile of iPSC-derived motor neuron lines generated from ALS patients and healthy controls as part of the Answer ALS program.

As phase 1 of the Earth Microbiome Project, analysis of 16S ribosomal RNA sequences from more than 27,000 environmental samples delivers a global picture of the basic structure and drivers of microbial distribution.

In South Africa, GM white maize has been grown for direct human consumption, whereas GM yellow and conventional hybrid maize have been cultivated primarily for livestock feed. Across 106 locations, 28 years, 491 cultivars, and 49,335 dryland and 9,617 irrigated observations in South Africa, GM maize showed increased mean yields over conventional hybrid maize, and GM white maize showed higher increased yields than GM yellow maize.

Neoantigen prediction from clinical samples is improved using a neural network model trained on a large HLA peptide and genomic tumor dataset.

Studies of mice and humans suggest a role for loss of the C9orf72 protein in some neurodegenerative disorders: with reduced C9orf72 levels, there is more inflammation mediated by the STING protein in immune and brain cells.

Extensive genomic analyses of the chromatin architecture in acute myeloid leukaemia reveals several characteristics, including subtype-specific distal enhancers and silencers, that may represent new anticancer therapeutic targets.

The Cancer Genome Atlas consortium reports on their genome-wide characterization of somatic alterations in colorectal cancer; in addition to revealing a remarkably consistent pattern of genomic alteration, with 24 genes being significantly mutated, the study identifies new targets for therapeutic intervention and suggests an important role for MYC-directed transcriptional activation and repression.

Whilst estrogen is known to be tumorigenic in some breast cancer, in some contexts it can be protective against invasion and dissemination. Here, the authors show estrogen can promote generation of Suppressive Cortical Actin Bundles that can inhibit motility dynamics through EVL-mediated actin cytoskeletal remodeling.

HIV particles contain a relatively low amount of viral envelope (Env), but underlying packaging mechanisms are poorly understood. Here, the authors use superresolution microscopy and show that Env distribution is biased toward the necks of cell-associated particles during assembly.

Local zoning ordinances may impact wind and solar development in the United States. A new study finds that setbacks could reduce resource potential by up to 87% for wind and 38% for solar.

The authors describe an integrated atlas of the diverse cell types in the mouse primary motor cortex.