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Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst formation and loss of kidney function, yet prognostic biomarkers remain limited. Here, the authors show that serum proteomics identifies protein signatures associated with disease severity, enabling improved risk prediction and stratified management.

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.

Lolamicin, a novel antibiotic developed from a pyridinepyrazole precursor, exhibits potent activity against a broad range of Gram-negative multidrug-resistant clinical isolates, and good efficacy in mouse models of infection without inducing gut dysbiosis.

The enzyme Rubisco has a central role in atmospheric CO₂ fixation. Rubisco can be inactivated if its sugar substrate is bound prior to carbamylation of a residue in the active site. The structure of tobacco Rca, the enzyme that removes the bound sugar substrate and activates Rubisco, is now presented, offering insight into this process.

Electrophysiology experiments on reconstituted membranes provide functional information on membrane proteins. Protocols for Montal-Mueller and Mueller-Rudin bilayers, or for formation via giant liposomes are presented and compared.

A high-resolution, global atlas of mortality of children under five years of age between 2000 and 2017 highlights subnational geographical inequalities in the distribution, rates and absolute counts of child deaths by age.

The mechanism of action of daptomycin, a lipopeptidic antibiotic, is unclear. Here, the authors show that Ca²⁺-daptomycin simultaneously interacts with lipid-coupled precursors of the bacterial cell envelope and with the anionic phospholipid phosphatidylglycerol, forming a tripartite complex.

Hofer et al. show that fasting promotes the synthesis of spermidine, which stimulates eIF5A hypusination to induce autophagy and increase lifespan in various species in a conserved manner.

MethyLYZR, an epigenetic classifier of brain tumors, provides clinically relevant cancer classification results within 15 min of sequencing, with potential applications for neurosurgical intraoperative use.

Keyl et al. present an explainable artificial intelligence model-based real-world data analysis from over 15,000 patients across 38 cancer types, identified key prognostic marker interactions, and confirmed these in an external lung cancer cohort.

Design of efficient catalysts requires understanding the decisive electronic parameters for catalytic efficacy and their dependence on elemental composition. Here, the authors report covalency as suitable descriptor of perovskite-type transition metal oxides as chemo-catalysts.

Many bacteria release DNA and membrane vesicles through unclear mechanisms. Here, the authors show that a prophage endolysin is involved in the explosive lysis of a sub-population of cells in Pseudomonas aeruginosa, releasing cytoplasmic content and membrane fragments that rapidly form membrane vesicles.

Fungus-growing ants cultivate fungi for food, but it is unclear whether single ant and fungal species are exclusive to one another. This study ofC. wheeleriants and their fungi shows that each ant species has been associated with a single fungal cultivar species for millions of years and that ant speciation coincides with shifts in fungal use.

Although progress in the coverage of routine measles vaccination in children in low- and middle-income countries was made during 2000–2019, many countries remain far from the goal of 80% coverage in all districts by 2019.

Here the authors show efficacy of a low-dose, unmodified, bivalent mRNA vaccine against SARS-CoV-2 variants in two female rodent models and find that combination of mRNA encoding Beta and Delta Spike sequences induces broadly neutralizing antibodies and robust T-cell responses.

SUMOylation is a post-translational modification that has been shown to be altered in cancer. Here, the authors show that loss of the SUMO isopeptidase SENP6 leads to unrestricted SUMOylation and genomic instability promoting lymphomagenesis and generating vulnerability to PARP inhibition.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

Chitin degrading bacteria are important for marine ecosystems. Here the authors structurally and functionally characterize the Vibrio harveyi outer membrane diffusion channel chitoporin and give mechanistic insights into chito-oligosaccharide uptake.

Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.

Emerging SARS-CoV-2 variants with mutations in the spike protein raise concerns regarding vaccine efficacy. Here, the authors show that two spike encoding mRNA vaccines in preclinical and clinical development protect human ACE2 mice from the B.1.351 variant of concern and ancestral B BavPat1.

Climate change is expected to intensify the global hydrological cycle and to alter evapotranspiration, but direct observational constraints are lacking at the global scale. Now a data-driven, machine-learning technique and a suite of process-based models have been used to show that from 1982 to 1997 global evapotranspiration increased by about 7.1 millimetres per year per decade. But since 1998 this increase has ceased, probably because of moisture limitation in the Southern Hemisphere.

Biodiversity often increases the functioning and productivity of ecosystems or communities. This work shows that such a positive diversity effect, namely overyielding in mixtures of two divergent Arabidopsis thaliana genotypes, can be genetically mapped and resolved to a single gene.

Merz and colleagues perform single-cell multiomic analysis of mononuclear cells isolated from individuals receiving BCMA-directed CAR T cell therapy for myeloma and show that nonresponders are characterized by an immune-suppressive microenvironment.

High-resolution subnational mapping of child growth failure indicators for 105 low- and middle-income countries between 2000 and 2017 shows that, despite considerable progress, substantial geographical inequalities still exist in some countries.

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.

The most up-to-date combination of results on the properties of the Higgs boson is reported, which indicate that its properties are consistent with the standard model predictions, within the precision achieved to date.

The CMS Collaboration reports evidence for off-shell Higgs boson contributions in the production of Z boson pairs, and measures the width of the Higgs boson, which is inversely related to its lifetime.

Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by aggregation of Tau, encoded by MAPT. Here, the authors perform an EWAS for PSP in prefrontal lobe tissue and find hypermethylation of DLX1 and its antisense transcript DLX1AS to associate with MAPT expression.

Ribosome biogenesis is tightly coordinated with cell-cycle progression. By characterizing the SUMO isopeptidases SENP3/SENP5, Doenig et al. identify a long-sought p53-independent impaired ribosome checkpoint that converges on downregulation of CDK6.

An online approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups has been developed to help to improve current diagnostic standards.

Schumacher and colleagues find that the FOXO transcription factor DAF-16 is activated in response to DNA damage in C. elegans and promotes developmental growth in a manner involving EGL-27.

Single-molecule fluorescence in situ hybridization and live-cell imaging are used to study the contribution of transcriptional noise to stem cell heterogeneity, revealing that stochastic transcription dynamics are conducive to concomitant stem-cell maintenance and tissue homeostasis.

How the substrate specificity of fatty aldehyde dehydrogenase (FALDH) towards long-chain aldehydes is achieved is an unresolved question. Here the authors present a crystal structure of human membrane-bound FALDH and find that it contains a ‘gatekeeper’ helix that directs substrate specificity towards long-chain fatty aldehydes.