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Here the authors report the formation of toxic clumps of protein, similar to amyloid assemblies found in Alzheimer’s disease and suggest their possible role for some of the neurological symptoms of long-COVID.

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.

A new study shows the total global SOC stock of 1 m in the world’s tidal marshes to be 1.44 Pg C. On average, SOC in tidal marshes’ 0–30 cm and 30–100 cm soil layers are estimated at 83.1 Mg C ha⁻¹ and 185.3 Mg C ha⁻¹, respectively.

The genome of the malaria parasite Plasmodium falciparum contains a record of past evolutionary forces. Here, using 2537 parasite sequences from the Democratic Republic of the Congo, the authors demonstrate how drug pressure and human movement have shaped the present-day parasite population.

Prognosis is poor for tumours with Y-chromosome loss. Examining the interplay between cancer and immune cells sheds light on potential mechanisms.

A phase I trial of a neoantigen-targeting personalized cancer vaccine led to durable and polyfunctional T cell responses and antitumour recognition, and was associated with no recurrence in patients with high-risk clear cell renal cell carcinoma.

In the observational ZERO Childhood Cancer Precision Medicine Program PRecISion Medicine for Children with Cancer (PRISM) trial, children with high-risk cancer were treated with molecular tumor board-recommended therapies, resulting in overall clinical response rates that translated into survival benefit after long-term follow-up.

Al-Refaie et al. show that fasting induces spatial reorganization of chromatin and formation of chromatin rings in an mTORC1- and RNA Pol I-dependent manner in the C. elegans intestine.

Mosquito salivary glands and malaria parasites exhibit daily rhythms, which impact blood feeding and sporozoite gene expression.

Polymers are known to spontaneously produce micro- and nanoplastics but the mechanisms by which environmentally-triggered Å-level random bond breaking events lead to the formation of these relatively large fragments are unclear. Here, the authors show that chain scission accumulates in the amorphous phase of a semicrystalline morphology which leads to mechanical failure and the concurrent release of nanoplastics even under quiescent conditions.

X-ray synchrotron measurements reveal heterogeneities at electrode|electrolyte interfaces of lithium metal batteries operating at high potentials. Here the authors demonstrate the rearrangement of ionically conductive phases in polymer electrolytes that lead to battery performance degradation.

Water quality monitoring stations are crucial to ensure a timely response to any problem emerging across water resource networks. A study of nutrient monitoring of surface waters in the South Atlantic-Gulf region shows an inhomogeneous monitoring station distribution, with fewer stations in highly vulnerable areas.

This Analysis estimates the health benefits and economic value of enhancing social determinants of mental health in Brisbane South, Australia, home to 1.2 million people. Crosland et al. analyze the impact of a 5% improvement in social cohesion, childhood difficulties, substance misuse, unemployment, underemployment, homelessness and staying engaged with education over 11 years.

Proliferative and effector functions of T cells are determined by T cell receptor signalling and modulated by activator and inhibitory co-receptors. Authors report here that the G-protein-coupled receptor GPR171 functions as a co-inhibitor of T cell signalling and might serve as a target for cancer immunotherapy.

Snakebite is a life-threatening neglected tropical disease that is currently treated using different antibody-based antivenoms, each effective against bites of specific snake species, but not others. Here, the authors show that a combination of two toxin-inhibiting repurposed drugs provides broad protection in experimental animals against the lethal effects of snakebites from multiple snake species.

It is unknown why infant acute lymphoblastic leukemia (ALL) produced by MLL rearrangements leads to worse outcomes than childhood ALL. Here the authors develop a CRISPR-Cas9-induced human xenograft model of MLL-AF4 infant-ALL that faithfully replicates the disease and reveals that fetal-specific genes are potential infant-ALL drivers.

The PNUTS-PP1 complex directly binds to RNA, and interacts with polymerase II and RNA processing factors to control transcriptional elongation rates and slow polymerase II after polyadenylation sites to promote termination. Using a genome-wide CRISPR screen, Devlin et al. identify this complex as a critical suppressor of herpesvirus KSHV gene expression. They further provide evidence that PNUTS-PP1 controls elongation both downstream and upstream of polyadenylation sites on specific viral genes.

Evolutionary modelling and expert review are applied to integrate experimentally supported knowledge accumulated in the Gene Ontology knowledgebase to create a draft human gene ‘functionome’.

Analyses of the genetic architecture of the human plasma metabolome in two large population-based cohorts identify associations between genetically determined metabolite levels and health.

DiNardo et al. perform a phase 1b/2 clinical trial of telaglenastat (CB-839) in combination with azacytidine in persons with advanced myelodysplastic syndromes and report on the treatment safety and efficacy, including a definition of clinical responders.

In this work, the authors provide mechanistic insights for understanding the sodium-dependent, bacterial flagellar stator unit PomAB ion selectivity, directional rotation, and rotor incorporation in Vibrio spp.

The globally distributed marine tubeworm Hydroides elegans is emerging as a powerful model for studying bacteria-induced metamorphosis, and offers insights into developmental biology, marine ecology and host–microbe interactions.

Crossing the blood–brain barrier in primates is a major obstacle to gene delivery in the brain. Here an adeno-associated virus variant (AAV.CAP-Mac) is identified and demonstrated for crossing the blood–brain barrier and delivering gene sequences to the brain of different non-human primates species.

A genomic constraint map for the human genome constructed using data from 76,156 human genomes from the Genome Aggregation Database shows that non-coding constrained regions are enriched for regulatory elements and variants associated with complex diseases and traits.

The MET receptor is frequently activated in cancer. Here, the authors show that in head and neck and lung squamous carcinoma, a polymorphic MET variant enhances binding to HER2, resulting in activation of HER2 signalling and progression of the cancers.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Most functional genomic resources have been based on individuals with European ancestry. Here, the authors perform DNA methylation quantitative trait locus (mQTL) analyses in 3,701 European and 2,099 East Asian individuals to identify thousands of genetic variants, a large degree of which are shared between the two populations.

The ESCRT pathway is crucial for membrane remodelling in eukaryotes. Here, Hatano et al. explore the phylogeny, structure, and biochemistry of homologues of the ESCRT machinery and the associated ubiquitylation system in Asgard archaea, the closest living relatives of eukaryotes.

Curiosity is motivated by uncertainty and valence, but how uncertainty and valence are encoded in the brain remains poorly understood. Here, the authors show that parietal neurons are enhanced by both factors, but that they specifically predict visual information seeking based on uncertainty.

Selective protein degradation in disease-relevant cells or tissues has seen limited success. Hence, the authors develop Folate Receptor Targeting Chimeras (FRTACs) to specifically target proteins in cancer cells, aiming to reduce on-target, off-tumor toxicity.

A 4 °C global temperature increase would push 7.5% of amphibian species beyond their physiological limits.

Characterization of clinical isolates of the cryptic fungal pathogen Aspergillus latus revealed traits that distinguish it from other species. Steenwyck et al show that A. latus originated via allodiploid hybridization with both parental subgenomes actively expressed.

PD-1 is a critical modulator of CD8⁺ T cell activation and exhaustion. Sen and colleagues show that a cell-state-specific enhancer tunes PD-1 expression exclusively in exhaustion and that deletion of this enhancer improves CD8⁺ T cell function.

Gene duplication and subsequent paralogue diversification are major obstacles to genotype-to-phenotype predictability.

Cellular target engagement technologies enable quantification of intracellular drug binding, but the simultaneous assessment of drug-associated phenotypes is challenging. Here, the authors develop CeTEAM (cellular target engagement by accumulation of mutant), a platform that can simultaneously evaluate drug-target interactions and phenotypic responses for holistic assessment of drug pharmacology using conditionally stabilized drug biosensors.

Ji and colleagues show that the specific angiosperm growth-governing DELLA–SLY1/GID2 protein interaction evolved from a broader ancestral affinity, suggesting affinity narrowing to be a general evolutionary driver of interaction specificity.

Increased longevity of diet-restricted Caenorhabditis elegans requires the transcription factor gene skn-1 acting in the ASIs, a pair of neurons in the head. Dietary restriction activates skn-1 in the ASIs, which signals peripheral tissues to increase metabolic activity. These findings demonstrate that increased lifespan in a diet-restricted nematode depends on signalling from central neuronal cells to non-neuronal body tissues, and suggest that the ASIs mediate dietary restriction-induced longevity by an endocrine mechanism.

Size control in quantum materials by direct growth is still difficult to achieve. Here, the authors present the width-dependent growth of single-layer nanoribbons of transition metal dichalcogenides from nanoalloy seeds, achieving strain-induced quantum emission with a purity of up to 90 % for single photons.