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The cytoplasm can be partitioned into distinct compartments by microtubule structures, which can be stabilized by distinct mechanisms in different species.

iGluSnFR4f and iGluSnFR4s are the latest generation of genetically encoded glutamate sensors. They are advantageous for detecting rapid dynamics and large population activity, respectively, as demonstrated in a variety of applications in the mouse brain.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

To mark the occasion of Nature Chemistry turning 10 years old, we asked scientists working in different areas of chemistry to tell us what they thought the most exciting, interesting or challenging aspects related to the development of their main field of research will be — here is what they said.

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.

With the yearly exodus from labs and lecture theatres imminent, Nature's regular reviewers and editors share some tempting holiday reads.

The CMS Collaboration reports the study of three simultaneous hard interactions between quarks and gluons in proton–proton collisions. This manifests through the concurrent production of three J/ψ mesons, which consist of a charm-quark–antiquark pair.

Endoplasmic reticulum exit sites (ERES) are specialized ER subdomains that regulate the export of secreted cargo. This Roadmap explores how ERES integrate biochemical and mechanical signals to coordinate trafficking and proposes a multidisciplinary strategy to investigate their function, including in disease.

Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.

Portugal's spending on research is near the lowest in western Europe. Can a single-minded lady with half a billion euros change things, asks Alison Abbott.

The genetic basis of metabolic diseases is incompletely understood. Here, by high-throughput phenotyping of 2,016 knockout mouse strains, Rozman and colleagues identify candidate metabolic genes, many of which are associated with unexplored regulatory gene networks and metabolic traits in human GWAS.

A multi-ancestry genome-wide association study for age at menarche followed by fine mapping and downstream analysis implicates 665 pubertal timing genes, such as the G-protein-coupled receptor 83 (GPR83) and other genes expressed in the ovaries involved in the DNA damage response.

The structure of nanoparticles strongly influences their properties. Here, the authors use single crystal X-ray diffraction to resolve the crystal structures of Ag₁₃₆ and Ag₃₇₄nanoparticles, enabling the observation of local structure distortion and the lower size limit of surface plasmon resonance.

The ER exit site component Sec16A was identified as the target of Retro-2, a small-molecule inhibitor of protein toxins and pathogens. Retro-2 treatment alters retrograde early/maturing endosomes-to-Golgi trafficking of Shiga toxin.

A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

Woody plants across the continental United States make extensive use of water stored in bedrock across diverse climates and biomes.

The sustainability of the majority of multispecies reef fisheries around the globe remains unassessed. This study provides context-specific sustainable reference points for coral reef fish using environmental conditions. Using these reference points, they show that most reef fish stocks have failed at least one fisheries sustainability benchmark.

Human behaviour is complex and multifaceted, and is studied by a broad range of disciplines across the social and natural sciences. To mark our 5th anniversary, we asked leading scientists in some of the key disciplines that we cover to share their vision of the future of research in their disciplines. Our contributors underscore how important it is to broaden the scope of their disciplines to increase ecological validity and diversity of representation, in order to address pressing societal challenges that range from new technologies, modes of interaction and sociopolitical upheaval to disease, poverty, hunger, inequality and climate change. Taken together, these contributions highlight how achieving progress in each discipline will require incorporating insights and methods from others, breaking down disciplinary silos.

Water thermodynamics drive changes in macromolecular assembly that rapidly restore intracellular water availability in response to physiological fluctuations in temperature, pressure and osmotic strength.

Genome-wide association meta-analyses identify 26 risk loci for epilepsy, including 19 loci specific to genetic generalized epilepsy. Prioritized candidate genes implicate synaptic processes and overlap with targets of antiseizure medications.

At a time when protecting the environment is urgent, dealing with inherent uncertainties in the responses of biodiversity to disturbances is essential. This study promotes a promising tool to assess the vulnerability of species assemblages to guide protection efforts even if species response and disturbance regimes are poorly documented.

Cox and colleagues develop PXS-5505, a first-in-class selective pan-lysyl oxidase inhibitor and show that it reduces chemotherapy-induced desmoplasia and stiffness, thereby improving chemotherapy response and survival in pancreatic cancer models.

Primary open-angle glaucoma (POAG) is highly heritable, yet not well understood from a genetic perspective. Here, the authors perform a meta-analysis of genome-wide association studies in 34,179 POAG cases, identifying 44 previously unreported risk loci and mapping effects across multiple ethnicities.

A multi-ancestry genome-wide association study of prostate cancer performed in 156,319 cases and 788,443 controls identifies 187 novel risk variants associated with the disease. Genetic risk scores associated with overall risk, and risk of aggressive disease in men of African ancestry.

Osmotic compensation by electroneutral ion transport buffers TORC1-mediated changes in the cytosolic proteome, and maintains intracellular homeostasis and cell volume over the circadian cycle. Here, the authors find such ion content changes drive daily rhythms in cardiomyocyte electrical activity.

Photonic methods can be greatly improved by metal nanoparticles, but biological targets such as cells prevent spatial control of particles, excluding key regions of interest. Here, the authors show laser light can control nanoparticle growth locations in the cell, and probe intracellular molecules.

Adipocyte-expressed long non-coding RNAs (lncRNAs) have been shown to regulate the transcription of genes involved in lipid metabolism. Here the authors describe a human adipocyte-specific lncRNA, ADIPINT, which regulates lipid metabolism in white adipocytes in part through its interaction with the metabolic enzyme pyruvate carboxylase.

In breast cancer, genome-wide associations studies (GWAS) have highlighted loci associated with disease risk. Here, the authors perform a meta-analysis of GWAS data from Asian populations, discovering 31 potential new risk loci, 10 of which are validated in an independent disease cohort.

Saville, Mannar et al. provide a structural basis for enhanced antibody evasion and ACE2 binding by the Delta SARS-CoV-2 spike protein. They further identify a head-to-head dimer-of-trimers cryoEM reconstruction unique to the Kappa variant spike.

Cellulose is synthesized as microfibrils of β-1,4-linked glucan chains arranged in a crystalline lattice. Here Ye et al. use grazing incidence wide angle X-ray scattering to show that cellulose crystals are preferentially orientated parallel to the plant cell wall, rather than as twisting microfibrils as previously hypothesized.

Inter- and intra-species comparison of Arabidopsis centromere variation identifies rapid cycles of transposon invasion and purging through satellite homogenization that drive centromere evolution.

In this Review, Holmes and colleagues explore the mechanisms by which healthcare functions as a driver, reservoir and amplifier of antimicrobial resistance (AMR), and they explore opportunities and innovative solutions to mitigate healthcare-associated AMR and promote healthcare resilience.

NF-κB transcription factors have been implicated in cellular transformation and tumorigenesis, but despite extensive biochemical characterization of NF-κB signalling, its requirement in tumour development is not completely understood. Here, the NF-κB pathway is shown to be required for the development of tumours in a mouse model of lung adenocarcinoma in a p53-status-dependent manner, providing support for the development of NF-κB inhibitory drugs as targeted therapies.

A study from the FANTOM consortium using single-molecule cDNA sequencing of transcription start sites and their usage in human and mouse primary cells, cell lines and tissues reveals insights into the specificity and diversity of transcription patterns across different mammalian cell types.

Neurodevelopmental disorders are frequently associated with synaptic dysfunction. Recent genome-wide association studies associate the gene encoding microRNA-137 with an increased risk for schizophrenia. Using mouse and human models, the authors show that dysregulation of this miRNA leads to presynaptic defects and, consequently, to impaired synaptic plasticity and cognitive dysfunction.

2024 marks twenty years of the educational website Not Voodoo: Demystifying Synthetic Organic Chemistry — a fount of knowledge for organic chemistry laboratory techniques, with tips and tricks for both beginning research students and advanced experimentalists. 

The adhesion receptor CD2 plays an important role in the full activation of T cells. Dustin and colleagues show that CD2 occupies a region in the periphery of the immunological synapse where it amplifies cognate antigen signals, whereas the presence of PD-1 disrupts this effect.

Decline in sensorimotor skills with age may be due to an overreliance on the prediction of the sensory consequences of one’s actions. Here the authors show that sensorimotor attenuation increases with age, and that this is associated with structural and functional changes in frontostriatal circuits.

The protective effect of vaccines is often poorest in low-income countries. Here, the authors explore the immunological factors that may explain the geographical variation in vaccine responsiveness and the ways in which they might be modulated to ensure effective vaccination in regions where it is needed most.