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In this paper, the authors present findings demonstrating that variations of the MET gene are associated with specific structural differences in key language regions in individuals with schizophrenia.

Normothermic machine perfusion (NMP) is increasingly used for preserving and evaluating donor livers before transplantation. Here, the authors demonstrate increased regenerative protein profiles in the bile of perfused livers considered suitable for transplantation, providing insight into the mechanisms linked to recovery of the biliary tree following ischemia-reperfusion injury.

Voetterl and colleagues examined the application of ‘Brainmarker-I’, an age- and sex-normalized electroencephalogram measure of individual alpha peak frequency, on predicting remission to therapeutic noninvasive neuromodulation protocols (repetitive transcranial magnetic stimulation and electroconvulsive therapy).

In this compassionate use study, treatment of adult patients with H3K27M-mutant diffuse midline glioma with a long peptide vaccine targeting H3K27M led to vaccine-induced peripheral T cell immune responses and encouraging clinical efficacy in the majority of patients, including a durable complete response.

The use of IL-17/IL-23 blocking therapy for rare inflammatory skin diseases needs proof of principle data for larger clinical trials. Here the authors show that patients with Darier disease have enhanced Th17 cells and, using IL-17/IL-23 blockers, they show that the immune gene signatures are altered in localised skin biopsies.

Cysteine bioconjugation is an important method to modify biomolecules, but synthetic efforts to diversify reactive warheads and the low reactivity of introducible linchpins often impede application in biological laboratories. Now, a thianthrenium-based reagent permits site-selective installation of episulfonium on biomacromolecules, enabling one-step addition of bioorthogonal nucleophiles and further applications in quantitative proteomics and cross-linking.

Genome-wide association meta-analyses of waist-to-hip ratio adjusted for body mass index in more than 224,000 individuals identify 49 loci, 33 of which are new and many showing significant sexual dimorphism with a stronger effect in women; pathway analyses implicate adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution.

Mucosal Associated Invariant T cells have been implicated in response to bacterial pathogens. Here the authors show that in human viral infections, these cells are activated by IL-18 in cooperation with other pro-inflammatory cytokines, producing interferon gamma and granzyme B.

Infant gliomas behave differently to their childhood or adult counterparts. Here, the authors perform a large-scale genetic analysis of these tumours, revealing genetic alterations which may offer therapeutic opportunities.

Cortex morphology varies with age, cognitive function, and in neurological and psychiatric diseases. Here the authors report 160 genome-wide significant associations with thickness, surface area and volume of the total cortex and 34 cortical regions from a GWAS meta-analysis in 22,824 adults.

Jayavelu, Samaha et al., apply machine learning models on hospital admission data, including antibody titers and viral load, to identify patients at high risk for Long COVID. Low antibody levels, high viral loads, chronic diseases, and female sex are key predictors, supporting early, targeted interventions.

Chronic UV exposure has been associated with immune system suppression. Here the authors show that enhanced tumor growth and resistance to PD1 blockade in mice exposed to UV irradiation is associated with induced expression of Ly6a in CD8 + T cells and that targeting Ly6a enhances anti-tumor immune responses in models resistant to anti-PD1.

Calorie burning is normally turned off in thermogenic brown fat at warm temperatures. Here the authors show that adipocyte oxygen sensing directly boosts brown fat calorie burning, even at warm temperatures.

A study using cryo-electron microscopy has determined the structure of the human dopamine transporter with bound cocaine, revealing molecular details about neurotransmitter transport and how it is affected by neuropsychiatric drugs.

Venomous animals typically disrupt nervous, locomotor, and cardiovascular systems to incapacitate prey, but certain fish-hunting cone snails evolved toxins that specifically target glucose homeostasis. Here, the authors show the combinatorial nature of weaponized insulin and somatostatin mimetics, exemplifying the use of combinatorial chemical mimicry for prey capture.

Effective CD8⁺ T cell immunity requires the generation of a long-lived memory pool and the maintenance of a non-exhausted effector T cell pool. The implementation of immune checkpoint blockade can reduced levels of exhaustion but lacks the ability to support memory formation in the effector pool. Here the authors suggest a role for Let-7 in the enhancement of the anti-tumor CD8⁺ T cell response by supporting memory via modulation of metabolic and differentiation state.

Neutrophilic inflammation is a hallmark of many monogenic autoinflammatory diseases. Here the authors report a case series of three unrelated boys with perinatal-onset of neutrophilic cutaneous small vessel vasculitis and systemic inflammation, and identify de novo truncating and missense variants in the Src-family tyrosine kinase LYN.

Resident macrophages of the muscularis externa refine the enteric nervous system (ENS) early in life by pruning synapses and phagocytosing enteric neurons, and later switch to a neuro-supportive function, indicating that the ENS is governed by a dedicated population of resident macrophages that adapt to the timely needs of the ENS.

Antibodies play a crucial role in protection from influenza virus infection, but functional details, particularly in older adults, are incomplete. Here the authors show that NK cell-activating antibodies are associated with protection from influenza infection in vaccinated older adults.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

Ruth Loos and colleagues report results of a large genome-wide association study for body mass index. They identify 18 new loci associated with this trait, some of which map near key hypothalamic regulators of energy balance.

Detection of topological phases in experiments is challenging, especially in the presence of incoherent noise. Cong et al. introduce a novel method combining error correction and renormalization-group flow and apply it to characterization of quantum spin liquid phases realized in a Rydberg-atom simulator.

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.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

Lipid concentration in the serum is one of the most important risk factors for coronary artery disease and can be targeted for therapeutic intervention. A genome-wide association study in >100,000 individuals of European ancestry now finds 95 significantly associated loci that also affect lipid traits in non-European populations. Among associated loci are those involved in cholesterol metabolism, known targets of cholesterol-lowering drugs and those that contribute to normal variation in lipid traits and to extreme lipid phenotypes.

In GWAS, waist-to-hip ratio (WHR) is often adjusted for body mass index (BMI) to account for their correlation (WHRadjBMI). Here, Winkler et al. classify 159 genetic variants for BMI, WHR, or WHRadjBMI based on their effect directions for BMI and WHR to differentiate subtypes of adiposity genetics.

Using an international collection of population-based microbiome studies of participants in the MicroCardio Consortium, a cross-cohort meta-analysis identified several phylogenetically diverse, species- and strain-level microbial features as well as community-level functional shifts encompassing diverse pathways to type 2 diabetes.

Mismatch repair-deficient colorectal cancer clones adapt their mutation landscape by toggling homopolymer sequences in MutS homolog 3 (MSH3) and MutS homolog 6 (MSH6). This increases the subclonal mutation rate and clonal diversity, favoring immune escape and tumor growth.

Analyses of individual shoot meristem transcriptomes in wild-type and mutant tomato, at high temporal resolution, produce remarkably precise information about gene expression patterns during the transition from vegetative to floral growth that translates into genetic hierarchies.

The authors use virtual reality tasks and a latent state modeling approach to demonstrate that the opposing control of behavior by striatal pathways is dependent on both task demands and changes in internal state.

Identifying causal variants and genes in genome-wide association studies remains a challenge, an issue that is ameliorated with larger sample sizes. Here the authors meta-analyze kidney function genome-wide association studies to identify new loci and fine-map loci to home in on variants and genes involved in kidney function.

A secure framework that harmonizes storage and querying of clinical and genetic data using blockchain technology was developed to support combined genotype–phenotype queries, improving transparency into how and when health information is used.

Vaccination regimens and the number of doses required for optimal immunity and protection are critical factors in the translation of vaccines. Here the authors show administration of a three dose protocol of a single T cell epitope to the SARS-CoV-2 spike protein induces a robust CD8⁺ T cell response and confers protection in a lethal murine challenge model of infection.

Molecular analyses of modern and fossil skeletal samples reveal that elevated metabolic rates consistent with endothermy evolved independently in mammals and plesiosaurs, and ornithodirans: Exceptional metabolic rates are ancestral to dinosaurs and pterosaurs and were acquired before energetically costly adaptations, such as flight.

The mechanism of flavivirus activation for membrane fusion is not yet understood. Here, Vaney et al. describe how the viral pr protein, derived from an HSP40/DnaJ chaperonin, interacts with a pH sensing loop in the envelope protein E for fusogenic activation.

B cells are engineered in vivo to secrete anti-HIV antibodies

Here, using fecal metagenomics data of 2,320 individuals, the authors develop a microbiome-based machine learning approach showing high accuracy for multi-class disease diagnosis, highlighting its potential application in improving noninvasive diagnostics and monitor responses to therapy.