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Though the complement system is pivotal in the defence against infections, pathologic activation of the system contributes to disease. Here, authors show that their recently developed monoclonal antibody against complement factor 2, empasiprubart, inhibits the classical and lectin pathways in a clinical trial, and its crystal structure provides basis for its inhibitory properties, such as Ca²⁺ binding.

Plant-parasitic nematodes have the potential to destroy crops globally, and limited options for managing nematode infestation are available. Here, the authors report the 1,3,4-oxadiazole thioether scaffold called Cyprocide that selectively kills nematodes including diverse species of plant-parasitic nematodes.

Here, Santamaria de Souza et al. explore the context-dependent fitness effects of glpT-deficiency in Salmonella enterica, showing mutants thrive in the gut lumen but are counter-selected by macrophages, highlighting antagonistic pleiotropy and niche-dependent adaptation.

This study introduces RNA origami nanotubes as self-assembling cytoskeleton mimics for synthetic cells. Expressed in vesicles from DNA templates, these RNA structures reach micrometre lengths, deform membranes and exhibit different phenotypes.

Nematodes use a characteristic set of movements, called nictation, to hitchhike on more mobile animals. Here, Lee et al. identify a genetic locus in the nematode Caenorhabditis elegans that underlies nictation and contributes to successful hitchhiking, but at expense of reduced offspring production.

Bacterial endonuclease V enzymes are characterized as DNA repair proteins. Here the authors show that human endonuclease V is an inosine-specific ribonuclease, indicating a role for this enzyme in normal RNA metabolism rather than DNA repair.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Using differences among strains as a model for inter-individual variation, this paper identifies a conserved metabolicadaptation in C. elegans that compensates for genetic variation.

Ascaroside pheromones reflect population density in Caenorhabditis elegans. Here, the authors show that variation in ascaroside receptor genes contributes to differences in pheromone responses in natural populations of C. elegans.

The genomes of 609 wild Caenorhabditis elegans strains isolated across the world reveal hyper-divergent regions, often shared among many wild strains, that are enriched for genes that mediate environmental response, which might have enabled the species to thrive in diverse environments.

An autonomous DNA-origami nanomachine powered by the chemical energy of DNA-templated RNA-transcription-consuming nucleoside triphosphates as fuel performs rhythmic pulsations is demonstrated. In combination with a passive follower, the nanomachine acts as a mechanical driver with molecular precision.

Bacterial pathogens have evolved intricate mechanisms to evade the human immune system, including the production of immunomodulatory enzymes. Here, the authors establish the mechanisms of recognition and specific deglycosylation of IgG antibodies by the multi-modular enzymes EndoS and EndoS2

Here, Miranda-Cervantes et al. identified pantothenate kinase 4 (PanK4) as a key regulator of muscle metabolism. Deleting PanK4 impairs fatty acid oxidation and glucose uptake, leading to glucose intolerance, while increasing PanK4 enhances glucose metabolism, highlighting its potential in promoting metabolic health.

Remdesivir is under evaluation for treatment of COVID-19 in clinical trials. Here, the authors report results of remdesivir treatment in a patient with COVID-19 and the genetic antibody deficiency XLA. They show a temporally correlated clinical and virological response, suggesting that remdesivir can reduce SARS-CoV-2 replication in patients.

Gene expression links genomic variation to organismal trait differences. Here, the authors identify regulatory loci underlying gene expression variation in C. elegans and demonstrate how this variation could impact other complex traits.

Ruth Loos and colleagues report a meta-analysis of genome-wide association studies in 181,171 individuals identifying 14 new loci associated with heart rate and test these for association with cardiac conduction, rhythm disorders and cardiovascular disease. Their experimental studies in Drosophila melanogaster and zebrafish models provide support for a role for 20 candidate genes at 11 of these loci in regulation of heart rate.

ALS is somewhat heritable, but the genetic basis is not completely understood. Here, the authors identify alterations in splicing in neurons associated with amyotrophic lateral sclerosis and uncover several associated genetic loci, with a potential link to nuclear pore defects.

Muscle mass is lost in patients with diabetes, which is associated with mitochondrial disfunction. Here they show that SLIRP maintains muscle mitochondria and that exercise training can compensate for SLIRP loss, improving mitochondrial function and quality control in muscle.

The mechanisms underlying the activity of non-receptor tyrosine kinase, TNK1, in cancers are unclear. Here the authors show that MARK mediates 14-3-3 and TNK1 interaction which restrains TNK1 activity, while the release of TNK1 from 14-3-3 leads to TNK1 activation through its interaction with ubiquitin and thus results in TNK1-mediated tumor growth in vivo

Leonid Kruglyak and colleagues report high-throughput selective sequencing of a worldwide collection of 200 wild C. elegans strains, providing a comprehensive characterization of genetic variation in this species. They find that chromosome-scale selective sweeps have acted to reduce genetic variation and shape the C. elegans population structure in recent history.

Integrated data, including 100 human genomes from the Mesolithic, Neolithic and Early Bronze Age periods show that two major population turnovers occurred over just 1,000 years in Neolithic Denmark, resulting in dramatic changes in the genes, diet and physical appearance of the local people, as well as the landscape in which they lived.

An analysis involving the shotgun sequencing of more than 300 ancient genomes from Eurasia reveals a deep east–west genetic divide from the Black Sea to the Baltic, and provides insight into the distinct effects of the Neolithic transition on either side of this boundary.

In this study, the authors investigate immune responses following a third (booster) SARS-CoV-2 vaccination dose in a cohort of healthcare professionals in Denmark. They find stronger immune responses among those with a prior infection, and correlation between lower antibody responses and higher risk of subsequent breakthrough infection.

Several routes designed to induce a bandgap opening in graphene have been proposed. It is now demonstrated that hydrogen adsorption on the Moiré pattern induced by an iridium substrate can induce a bandgap of 450 meV.

Kupper and colleagues introduce the T-cell fraction as a molecular assessment of T-cell-mediated antitumor responses in primary melanomas that can predict metastatic recurrence.

Results from the phase 2/3 clinical trial of gantenerumab or solanezumab in dominantly inherited Alzheimer’s disease reveal no beneficial effects on cognitive measures despite a significant reduction in amyloid plaques and other key biomarkers in those treated with gantenerumab.

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology.

Analysis of HbA1c and FPG levels across 117 population-based studies demonstrates regional variation in prevalence of previously undiagnosed screen-detected diabetes using one or both measures and suggests that use of elevated FPG alone could underestimate diabetes prevalence in low- and middle-income countries.

Two high-affinity proton-dependent transporters of glucosinolates have been identified in Arabidopsis and termed GTR1 and GTR2; these transporters are essential for transporting glucosinolates to seeds, offering a means to control the allocation of defence compounds in a tissue-specific manner, which may have agricultural biotechnology implications.

This study investigates the dynamics of immunological markers after first SARS-CoV-2 vaccination dose in cohort of healthcare professionals in Denmark. Natural infection was associated with higher antibody responses, and IgG decline varied by age, sex, T-cell response, previous infection, and interval between vaccine doses.

The North Water polynya is a unique but vulnerable ecosystem, home to Indigenous people and Arctic keystone species. New palaeoecological records from Greenland suggest human abandonment c. 2200–1200 cal yrs BP occurred during climate-forced polynya instability, foreshadowing future ecosystem declines.

A cross-scale analysis of paired-stressor effects on biological variables of European freshwater ecosystems shows that in 39% of cases, significant effects were limited to single stressors, with nutrient enrichment being the most important of these in lakes. Additive and interactive effects were similarly frequent (ca. 30% each), this frequency being independent of the spatial scale of analysis for lakes but increasing with scale for rivers.

Soil microbiota can increase crop resilience to abiotic stressors. Here the authors show that Streptomyces produce bioactive spiroketal polyketides to enhance plant growth under drought and salt stress.

A hallmark of diverticular disease is pouches in the bowel wall which can become infected and inflamed, causing the more severe diverticulitis. Here, the authors report the first genome-wide association study on these interconnected conditions and identifyARHGAP15, COLQ and FAM155Aas novel risk loci.

Dimethyl fumarate (DMF) is a major drug in the treatment of psoriasis and multiple sclerosis. Here the authors reveal a mechanism of RSK/MSK inhibition through covalent inhibition that can explain the observed clinical effects and the dose–response characteristics of DMF treatment.

Two below-threshold surface code memories on superconducting processors markedly reduce logical error rates, achieving high efficiency and real-time decoding, indicating potential for practical large-scale fault-tolerant quantum algorithms.

Using the FANTOM5 CAGE expression atlas, the authors show that bidirectional capped RNAs are a signature feature of active enhancers and identify over 40,000 enhancer candidates from over 800 human cell and tissue samples across the whole human body.

Even genetically identical organisms in homogeneous environments vary, indicating that randomness in developmental processes such as gene expression may generate phenotypic diversity. Intestinal specification in the nematode Caenorhabditis elegans, in which wild-type cell fate is invariant and controlled by a small transcriptional network, is now studied. The results demonstrate that mutations in developmental networks can expose stochastic variability in gene expression, leading to phenotypic variation.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.