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Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Kim, Wang, Clow and colleagues show that long-range chromatin loops bringing distal enhancers or super-enhancers together with promoters are cohesin dependent and cell type specific, whereas most short-range and promoter-centric transcriptional loops are cohesin independent and constitutive.

The accumulation of chemoreceptor proteins at bacterial poles is thought to depend on their clustering into arrays. Strahl et al. show that in Bacillus subtilis, the chemoreceptor TlpA uses high membrane curvature as a spatial cue for polar localization, through the intrinsic curvature sensitivity of the receptor complex.

The authors in this work identify an in vivo CNS active bifunctional degrader of GSK3. This was discovered via development of orthogonally reactive linker chemistry and a direct-to-biology screen that was able to provide hits of in vivo chemical probe quality.

Age-related macular degeneration (AMD) is a common cause of vision loss with a large genetic risk in older individuals. Here, for a high-risk AMD subtype, the authors identify an association with a chromosome 10 risk region containing a long non-coding RNA.

Combination immunotherapy approaches might be effective in inducing sustained control of HIV by slowing rebound and improving CD8⁺ T cell responses.

Circadian clocks enable organisms to anticipate daily cycles, while being robust to molecular and environmental noise. Here, Eremina et al. show how the cyanobacterial clock buffers genetic and environmental perturbations through its core phosphorylation loop, and demonstrate that known clock regulators are dispensable for clock robustness.

The extracellular secreted NS1 (sNS1) is a major factor contributing to dengue hemorrhagic fever. Here, Shu et al. report sNS1 exists in multiple oligomeric states and presents a tetrameric structure.

Here, using pre-HIV-infection and non-HIV samples in a multi-modal study of microbiomes and metabolomes, the authors develop a taxon-specific measure of DISruption in COrrelations (DISCO) revealing system-wide dysbiosis preceding HIV-1 infection in men who have sex with men.

South American cordilleran orogenic systems have repeated complex magmatic and deformation histories. Here the authors analyze detrital zircons found in the Amazon deep-sea fan that record mountain-building events and reveal cycles of orogenesis with periods of ~60–90 Myr since the Phanerozoic.

Keypoint-MoSeq is an unsupervised behavior segmentation algorithm that extracts behavioral modules from keypoint tracking data acquired with diverse algorithms, as demonstrated in mice, rats and fruit flies. The extracted modules faithfully reflect human-annotated behaviors even though they are obtained in an unsupervised fashion.

An oestrus cycle-dependent hypothalamic line attractor is discovered to encode the dynamics of female mating behaviour.

Preclinical studies for amyotrophic lateral sclerosis are challenging. Here, the authors propose a device mounted on the skin of animals that mitigates electromyography signal contamination and offers high precision in monitoring drug effects on dysphagia-responsible bulbar muscles.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

The complex patterns of activity in motor cortex that control movements such as reach and grasp are dependent on both upstream neuronal activity in the thalamus and the current state of the cortex.

DNA interstrand crosslinks induced by acetaldehyde are repaired by both the Fanconi anaemia pathway and by a second, excision-independent repair mechanism.

This Article reports the emergence of SARS-CoV-2 escape mutations during bamlanivimab therapy in the setting of a phase II clinical trial.

A cross-sectional study from four African countries shows the importance of investigating the gut microbiome in previously under-represented populations and provides a framework for equitable microbiome research.

In this Review, Nicholas Chew and colleagues use epidemiological data on the cardiovascular–liver–metabolic disease syndemic to illustrate current and future projections on the burden of these diseases and their risk factors, and propose a unified framework for integrating and implementing effective multisystem interventions to tackle key components of this syndemic.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

The naked mole-rat exhibits extreme longevity, resistance to hypoxia and absence of cardiovascular disease. Here, Faulkes et al. identify mechanisms behind these traits by comparing cardiac metabolomes and transcriptomes of naked more-rats to other African mole-rat genera and evolutionary divergent mammals.

Ad-sig-hMUC1/ecdCD40L is a recombinant adenovirus vaccine comprising human MUC1 antigen fused to the extracellular domain of the CD40 ligand. Here the authors report the result of a phase I clinical trial of Ad-sig-hMUC1/ecdCD40L in patients with advanced adenocarcinoma.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Bacteria can form organized multicellular communities through regulation of cell growth, motility, shape and differentiation. Here, Ellison et al. show that bacterial multicellular development can also be driven by specific patterns of localization of appendages known as type IV pili.

The influence of pregnancy on Long COVID is not well understood. Here, the authors use electronic health record data from the United States to compare the incidence of Long COVID in females after infection in pregnancy with matched non-pregnant females of reproductive age.

Approximately a quarter of the human genome consists of gene deserts. Here, Abassah-Oppong et al. reveal the biological relevance, embryonic functions and underlying enhancer architecture of a genomic gene desert flanking the Shox2 transcription factor essential for limb, craniofacial and cardiac pacemaker development.

USP30 has been proposed to regulate mitophagy, a relevant Parkinson’s disease mechanism. Here, the authors show that Usp30 knockout mice and USP30 inhibitors like MTX115325 demonstrate neuroprotective responses in an alpha-synuclein mouse model of Parkinson’s disease.

Although defects in nucleocytoplasmic transport (NCT) may be central to the pathogenesis of ALS, the molecular mechanisms modulating the nuclear pore function are still largely unknown. Here, authors show that genetic and pharmacological modulation of actin polymerization disrupts nuclear pore integrity and can be targeted to rescue nuclear pore instability and dysfunction caused by mutant PFN1 as well as by C9ORF72 repeat expansion

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

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

This carefully designed study demonstrates that CagriSema overcomes metabolic adaptation in response to weight loss in rats.

Qi et al. used cryo-electron microscopy to determine the structures of tau filaments from the brains of individuals with MAPT mutants V337M and R406W, known to give rise to frontotemporal dementias. They showed that the tau filaments adopted the Alzheimer fold.

Stabilizing pegRNAs with 3′ RNA structures increases prime editing efficiency.

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.