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A combination of high-resolution spatial imaging, spatial proteomics and transcriptional data reveals sparse and heterogeneous bacterial signals in gliomas and brain metastases.

The genetic architecture underlying brainstem regions and how this links to common brain disorders is not well understood. Here, the authors use MRI and GWAS data from 27,034 individuals to identify genetic and morphological brainstem features that influence common brain disorders.

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.

Using structural MRI data from 45,615 individuals aged 3–96 years, Kaufmann and colleagues reveal that common brain disorders are associated with heritable patterns of apparent aging of the brain.

Genomic studies often lack representation from diverse populations, limiting equitable insights. Here, the authors show that the BIG Initiative captures extensive genetic diversity and reveals ancestry-linked health disparities in a community-based Mid-South cohort.

Genome-wide association analyses of migraine and its subtypes identify new susceptibility loci, including rare variants with large effects implicating PRRT2, SCN11A and KCNK5.

Amyloid aggregation of mutant p53 contributes to its loss of tumor suppressor function and oncogenic gain-of-function. Here, the authors use a protein mimetic to abrogate mutant p53 aggregation and rescue p53 function, which inhibits cancer cell proliferation in vitro and halts tumor growth in vivo.

Stroke is a multifactorial disease influenced by genetic and environmental factors. Here, the authors apply exome-wide association analysis to find rare coding variants associated with stroke in a Pakistani cohort, finding a significant association of a variant in NOTCH3 that is highly enriched in South Asians.

In situ cryoEM and modelling of the Campylobacter jejuni flagellar motor characterize the periplasmic scaffold and the structural basis for increased torque generation.

A genome-wide association meta-analysis study here shows novel genetic loci to be associated to body fat percentage, and describes cross-phenotype association that further demonstrate a close relationship between adiposity and cardiovascular disease risk.

α-Synuclein accumulation in putaminal synapses is hypothesised to drive Parkinson’s disease progression. This study demonstrates synaptic pSer129 α-synuclein enrichment in early-stage Parkinson’s disease, and its link with dopaminergic denervation and cortical Lewy body pathology.

The small RNA RepG modulates expression of chemotaxis receptor TlpB in Helicobacter pylori by targeting a length-variable G-repeat in the tlpB mRNA. Here, Pernitzsch et al. show that RepG also gradually controls lipopolysaccharide biosynthesis, antibiotic susceptibility, and in-vivo colonization of the stomach, by regulating a gene that is co-transcribed with tlpB.

A multi-ancestry genome-wide gene–smoking interaction study identifies 13 new loci associated with serum lipids.

A genome-wide association study and Metabochip meta-analysis of body mass index (BMI) detects 97 BMI-associated loci, of which 56 were novel, and many loci have effects on other metabolic phenotypes; pathway analyses implicate the central nervous system in obesity susceptibility and new pathways such as those related to synaptic function, energy metabolism, lipid biology and adipogenesis.

The authors find that the hippocampus creates a spatial and predictive cognitive map, and show how orbitofrontal and hippocampal computations select these maps adaptively to guide novel choices.

A pool of quality control proteins (QC) maintains the protein-folding homeostasis in the cell, but its quantitative analysis is challenging. Here the authors develop a FRET sensor based on the protein barnase, able to quantify QC holdase activity and its ability to suppress protein aggregation.

There is currently no disease-modifying treatment for Parkinson’s disease, a common neurodegenerative disorder. Here, the authors use genetic variation associated with gene and protein expression to find putative drug targets for Parkinson’s disease using Mendelian randomization of the druggable genome.

The microanatomy of the axonal projections of olfactory sensory neurons from the olfactory epithelium to the olfactory bulb in a human enbloc specimen is visualized in a 3D reconstruction assembled by deep learning and high performance computing.

Values of choice options often change over time. Here, the authors show that during prospective decision making the entorhinal cortex encodes changing values using a grid-like representation, suggesting the formation of a cognitive value map.

Missense variants in RNA-binding proteins underlie many diseases. Here the authors report an oculopharyngeal muscular dystrophy caused by heterozygous frameshift mutations in HNRNPA2B1 that alter its nucleocytoplasmic transport dynamics and result in cytoplasmic accumulation of hnRNPA2 protein.

An analysis of 52 million births in 26 countries shows small reductions in preterm birth during the first to third months of lockdown. Further research is needed to examine causal pathways.

In mice aged 12–18 months, chronic administration of low-dose Δ⁹-tetrahydrocannabinol (THC) improves performance in behavioral learning and memory tasks, whereas a similar administration in younger mice (aged 2 months) impairs performance.

Joseph Gleeson and colleagues report that biallelic mutations in SNX14 cause a syndromic form of cerebellar atrophy marked by lysosome-autophagosome dysfunction. Their findings suggest a role for SNX14 in mediating lysosome-autophagosome fusion.

Down syndrome can be associated with major impairments in skeletal maturation and bone mass accrual, which increases the risk of fragility fractures. Here, the authors outline various endocrine and metabolic factors that could contribute to suboptimal bone health in children and adolescents with Down syndrome, review indications and limitations of bone density measurement in children and discuss available therapeutic strategies to improve bone health in such patients.

In this Perspective, the authors present a model of assessing urban environmental factors’ impact on mental health by using UrbanSat measures and data from adolescents in the ABCD Study.