Search

While the photoreceptor outer segments in the bird outer retina have access to oxygen, the inner retina operates under chronic anoxia, supported by anaerobic glycolysis in the retinal neurons.

TREM2 is an important AD risk factor playing essential roles in the microglial response to amyloid pathology. Here, authors show using a TREM2 reporter mouse that TREM2 levels are critical for efficacy of TREM2 agonism informing current clinical efforts.

Forests are essential for both climate change mitigation and biodiversity conservation, yet how to balance these goals in managed forests remains unclear. Here, using a Europe-wide dataset, the authors find that biodiversity increases with carbon stocks, but mostly when deadwood is included.

T-cell–mediated rejection (TCMR) remains a major cause of kidney transplant failure with incompletely understood mechanisms. Here the authors use single-nucleus RNA sequencing, spatial transcriptomics and immunofluorescence to show that injured kidney epithelial cell states associate with poor transplant outcomes after T-cell–mediated rejection.

Krisai et al. compare brain structure and cognitive function in elderly patients with and without atrial fibrillation using brain MRI and cognitive testing. They find that atrial fibrillation is associated with more brain lesions and lower cognitive function, but the cognitive impairment occurs primarily through direct effects of the arrhythmia rather than through brain damage.

Integrating complex multi-omics data for individual patient decision making can be challenging. Here, the authors develop Knowledge Connector as a decision support system to generate and document Molecular Tumor Board recommendations and support medical decision-making.

C-COMPASS is an open-source software designed to predict the spatial cellular distribution of proteins and lipids from cellular organelle profiling using a neural network-based regression model.

The West Antarctic Ice Sheet responded to different natural forcing mechanisms than the East Antarctic Ice Sheet through the mid-Pliocene due to a greater sensitivity to oceanic feedbacks, according to iceberg-rafted debris records and ice-sheet modelling experiments.

Highly pathogenic avian influenza H5N1 viruses cause mass mortality in birds and have infected over 50 mammalian species, including humans. Here, the authors report the use of a propagation-defective vesicular stomatitis virus replicon vaccine in captive birds, which provides protection against lethal H5N1 challenge.

Small cell lung cancer cells form functional synapses with glutamatergic neurons, receiving synaptic transmissions and deriving a proliferative advantage from these interactions.

Efficient lead optimization in drug discovery requires improving potency, synthetic accessibility, and physicochemical properties. Here, the authors utilize machine learning to screen large chemical spaces, demonstrating automated selection of optimized molecules to improve cycle times.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Karposi’s Sarcoma-associated herpesvirus (KSHV) infection is associated with malignancy in older infected humans. Here the authors characterise antigen presentation using a KSHV-specific CD4⁺ T cell-derived TCR in a mouse model and show that although KSHV-specific CD4⁺ T cells are difficult to detect in humans, antigen presentation is effective in vivo suggesting persistence and accumulation of these cells through antigen recognition.

Mendelian genetics posits equal transmission of alleles, but selfish alleles can bias the transmission of large genomic regions or entire chromosomes. This study reveals the evolution of large amplicons as a distinct genetic feature of chromosomes with selfish alleles.

Diamond colour centres are of interest for solid-state quantum technologies but obtaining an efficient spin-photon interface remains challenging. Here, the authors use resonant excitation under magnetic fields to optically access the electronic spin sublevels of silicon-vacancy centres in diamond.

This work investigates changes in regularity of crop failure, heatwave and wildfire exposure for different future climate scenarios. Major shifts in dominant periods are observed when moving from pre-industrial to current climate conditions.

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.

Müller-Tidow and colleagues demonstrate that hotspot DNMT3A mutations found in clonal hematopoiesis and acute myeloid leukemia render cancer cells sensitive to the DNMT1 inhibitor azacitidine through focal DNA demethylation, viral mimicry and interferon activation.

As presented at the ESMO Congress 2025, in the single-arm phase 2 IKF/AIO PHERFLOT trial, the perioperative combination of FLOT chemotherapy with anti-PD-1 and anti-HER2 monoclonal antibodies led to a pathological complete response rate of 48.4% in patients with resectable HER2+ esophagogastric adenocarcinoma, meeting the prespecified co-primary endpoint.

Plasma proteomics plays a key role in advancing clinical research and biomarker discovery. Here, the authors show in a large MSCoreSys multicenter benchmark study that DIA outperforms DDA, delivering robust, precise, and reproducible label-free protein quantification across sites.

Chemical systems with switchable molecular spins could allow the development of materials with controllable spintronic properties. Here, the authors show that nitric oxide coordination to cobalt(II)tetraphenylporphyrin on a nickel surface, followed by thermal dissociation, leads to off-on spin switching.

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.

Direct interaction between the small GTPase Rab7a and the cation channel TPC2 has been reported but the functional regulation is less clear. Here, the authors show that Rab7a enhances the activity of TPC2 to promote melanoma progression through the GSK3β/β-Catenin/MITF axis.

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.

Natural products have historically made a major contribution to pharmacotherapy, but also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization. This Review discusses recent technological developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — that are enabling a revitalization of natural product-based drug discovery.

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.

Heart failure with preserved ejection fraction (HFpEF), which can be driven by obesity and hypertension, has a high prevalence but limited treatment options. Here, the authors show that nitro-oleic acid restores mitochondrial function and improves heart failure symptoms in a mouse model of HFpEF.

Epstein–Barr virus infection generates a neuroinvasive B cell subset, which recruits activated T cells to the central nervous system, promoting multiple sclerosis.

A fault-tolerant, universal set of single- and two-qubit quantum gates is demonstrated between two instances of the seven-qubit colour code in a trapped-ion quantum computer.

Seismological and geodetic data are used together with a machine learning earthquake catalogue to reconstruct magma migration before and during the 2025 volcano–tectonic crisis at Santorini volcano, indicating a coupling between Santorini and Kolumbo.

Induced pluripotent stem cells (iPSCs) hold great potential for modelling human developmental processes and diseases. Here the authors induce human iPSCs to spontaneously form fully laminated three-dimensional retinal tissue containing functional photoreceptor cells.

The experimental investigation of relaxation times in graphene quantum dots has long been hindered by the limited tunability of these devices. Here Volk et. al.employ a device design to study this problem and report charge relaxation times of around 60–100 ns.

Hegazy and colleagues demonstrate that epithelial oncostatin M receptor expression drives gut inflammation and tumor formation.

Despite their differences, the rarer sarcoma CIC::DUX4 sarcoma (CDS) is typically treated with therapies developed for Ewing Sarcoma (EwS) with limited success. Here, the authors develop a co-clinical drug response profiling platform to establish patient-derived CDS and EwS tumoroids, identifying MCL1 inhibition as a promising therapeutic approach in CDS.

Müller-Tidow and colleagues perform a randomized clinical trial and show that administration of convalescent plasma improves COVID-19 outcome in patients with cancer who are unable to generate an adequate immune response.

Examining drivers of the latitudinal biodiversity gradient in a global database of local tree species richness, the authors show that co-limitation by multiple environmental and anthropogenic factors causes steeper increases in richness with latitude in tropical versus temperate and boreal zones.

Expression of TMPRSS2—a protease that activates SARS-CoV-2 for entry into cells—renders SARS-CoV-2 insensitive to chloroquine.

Climate change affects agricultural productivity. New systematic global agricultural yield projections of the major crops were conducted using ensembles of the latest generation of crop and climate models. Substantial shifts in global crop productivity due to climate change will occur within the next 20 years—several decades sooner than previous projections—highlighting the need for targeted food system adaptation and risk management in the coming decades.

The study reveals strikingly different nonlinear Rabi splitting dynamics in MoSe₂ monolayers and (Ga,In)As quantum wells, highlighting the pivotal role of Coulomb interactions in shaping light–matter coupling in two-dimensional semiconductors.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

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.

Aberrant redox homeostasis links lipid metabolism and cell death programs. Here, authors reveal how cell stress reduces growth factor signaling, enriching polyunsaturated fatty acids in phospholipids and sensitizing membranes to oxidative damage.

Here, the authors introduce a computational strategy for antimicrobial discovery that addresses the scarcity of large datasets. Based on data-driven representations of molecular structures, this framework uncovers new growth inhibitors of Staphylococcus aureus.

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.

CD123 expression on leukemic stem and progenitor cells (LSPCs) and leukemic blasts representing a promising therapeutic target. However previous CD123-targeting approaches had limited efficacy and safety concerns. The authors here evaluate the bispecific CD123/CD16A innate cell engager AFM28 and manifest its efficacy both in vitro and in vivo, which is mediated by NK cells.

A genome-wide association study and Metabochip meta-analysis of body mass index (BMI) detects 97 BMI-associated loci, of which 56 were novel, and many loci have effects on other metabolic phenotypes; pathway analyses implicate the central nervous system in obesity susceptibility and new pathways such as those related to synaptic function, energy metabolism, lipid biology and adipogenesis.

Kaiser et al. characterize the disordered extracellular N-terminus of a peptide-activated G protein-coupled receptor. They combine biophysical, biochemical, and computational methods to uncover its role in the activation of G protein and arrestin pathways.