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Disease heterogeneity complicates precision medicine, which focuses on single conditions and ignores shared mechanisms. Here the authors introduce ‘pan-disease’ analysis using a deep learning model on multi-organ data, identifying 11 AI-derived biomarkers that reveal new therapeutic targets and pathways, enhancing patient stratification for disease risk monitoring and drug discovery.

In a rat model of multiple sclerosis, β-synuclein-specific T cells induce inflammation and pathological changes in the grey matter of the central nervous system; these cells were also found in higher numbers in patients with multiple sclerosis, particularly those with a chronic progressive course.

A brain–heart–eye axis is generated through integration of multi-omics and multi-organ data from UKBB, BLSA, FinnGen and PGC, revealing phenotypic landscapes and genetic arcitectures of disease.

This study reveals how infections that increase long-term dementia risk can contribute to longitudinal brain volume loss and regulate immunological proteins in plasma, and which of these proteins may drive infection-specific neurodegeneration.

How and to what extent oligodendrocytes (OLs) contribute to learning and cognition is not well understood. Here, the authors show that the performance of mice in working memory-dependent cognitive tasks depends on OL genesis and is proportional to the number of OL precursors and OLs generated during training.

How to live happily ever after.

The bacterium that causes stomach ulcers and deadly gastric cancer, Helicobacter pylori, is disappearing in many developed countries. Many physicians see this as cause for celebration. But at least one researcher thinks the bacterium is more than just a pathogen. Cassandra Willyard investigates whether H. pylori may be preventing diseases as well as causing them.

Through circuit dissection in juvenile, adolescent and adult mice, Klune, Goodpaster and colleagues reveal multiple developmental switches in mPFC–NAc and mPFC–BLA pathways that underlie developmental transitions in threat avoidance behavior.

This work shows a distinct involvement of the meningeal layers in CNS autoimmunity. In animal models and in patients with multiple sclerosis, the leptomeninges were highly inflamed and showed structural changes, while the dura was only marginally affected.

For most people, a single bite from a parasite-infected tsetse fly can trigger a slow, agonizing and sometimes fatal disease known as African sleeping sickness. But new research shows that some people, as well as baboons and other great apes, are naturally resistant to infection. Cassandra Willyard awakens to the possibility of using existing immunity to engineer new therapies and transgenic livestock.

Soil macroporosity responds rapidly to climate variations and may induce wide-ranging changes in soil hydraulic conductivity by the end of the century.

The effective hygroscopicity of organic matter and inorganic ions in atmospheric aerosols can be efficiently and accurately parameterized by global average values to constrain a critically important aspect in climate and Earth system models

A challenge in psychiatric drug discovery is to predict the therapeutic potential of a novel compound. Here, the authors show that brain-wide imaging of immediate early gene expression can be used to classify a panel of drugs including psychedelics and antidepressants with high accuracy.

Here the authors show in female mice at mid-life that deletion of estrogen receptor β in astrocytes induced cognitive impairment, hippocampal atrophy, glial activation and synaptic loss. ERβ ligand treatment restored cognition and decreased neuropathology in these animals.

Researchers are enrolling thousands of participants around the world in clinical trials in a massive effort to test whether a once-daily pill can prevent HIV. Cassandra Willyard explores why they are optimistic the strategy will work and why it might be difficult to implement.

How mechanisms underlying food-web stability may influence ecosystem regime shifts is not well understood. Combining food-web and ecosystem modelling, Kuiperet al. show that destabilizing reorganization of a small number of key trophic interactions precede catastrophic changes in shallow lake ecosystems.

This study reports unexpected structural diversity in computationally designed protein assemblies due to subunit flexibility. Fixing flexibility in one design restores the intended architecture, suggesting a strategy to design dynamic assemblies.

New formulas, devices and tools are removing historical bias from medical diagnoses.

A shift towards more-frequent, less-intense fires in Australia began about 11,000 years ago due to management by Indigenous societies, according to charcoal and stable polycyclic aromatic hydrocarbon records extending back 150,000 years.

What makes some people more prone to depression and less likely to respond to the medicines that can treat it? Comparing the genetic makeup of thousands of people is uncovering some answers, reports Cassandra Willyard.

Intellectual property isn't something you can see or touch. Yet some companies are trying to sell medical patents the same way antiques dealers sell ancient coins or fine art—at live auctions. Will this new model work? Cassandra Willyard explores the weird world of intellectual property auctions.

A high-resolution gene expression atlas of prenatal and postnatal brain development of rhesus monkey charts global transcriptional dynamics in relation to brain maturation, while comparative analysis reveals human-specific gene trajectories; candidate risk genes associated with human neurodevelopmental disorders tend to be co-expressed in disease-specific patterns in the developing monkey neocortex.

We find that the optical emission due to ionized gas that is characteristic of a shock extends 40 kpc in diameter across the host galaxy of an odd radio circle.

In low- and middle-income nations, snakebite envenoming is more deadly than almost any other neglected tropical disease.

NAD + metabolism is potential target to treat metabolic disorders, in part due to the effects of the NAD + dependent enzyme Sirt1. Here the authors report that hepatic nicotinamide phosphoribosyltransferase, a rate-limiting step in the NAD + salvage pathway, regulates dark-cycle thermogenesis in a Sirt1-dependent but light-cycle thermogenesis and glucose homeostasis in a Sirt1-independent manner.

Du et al. genetically engineer bacteriophages into heterologous effector phage therapeutics, enabling dual phage- and effector-mediated targeting for a two-pronged attack against bacterial pathogens.

Electrical stimulation has promised huge gains for people with paralysis. Now comes the hard part — getting beyond those first steps.

In a replicated ecosystem-scale natural experiment across ten islands in the Indian Ocean, invasive black rats disrupted nutrients provided by seabirds, leading to a coral reef fish having larger territories and investing less time in aggression than on rat-free islands.

Engineered switchgrass and poplar are better feedstocks for biofuel synthesis and yield more biomass in multi-year field trials.

Although diagnosis of urinary tract infections has improved through the use of point-of-care molecular technologies, they are however limited by poor specificity and / or sensitivity, and requirement of laboratory resources. In this work, the authors develop a bacteriophage-based diagnostic assay for the detection of prevalent uropathogens.

Transcriptomic analyses of acute phase whole blood from a large cohort of patients with COVID-19 identify molecular determinants of post-infection long-term sequelae.

Researchers disagree over how bad it is to be reinfected, and whether COVID-19 can cause lasting changes to the immune system.

Spin qubits in systems with strong spin–orbit coupling can be electrically controlled, but are usually affected by short coherence times. Here, coherence times up to 10 ms are obtained for strain-engineered hole states bound to boron acceptors in silicon 28.

Recent electron microscopy techniques have attracted significant attention for their ability to image electric fields at the atomic level. Here, the authors investigate the possibility to separate the charge density contributions of core and valence electrons in monolayer MoS2, highlighting the limitations induced by the electron probe shape.

The evolution of germ cell specification by maternal germ plasm has been proposed to accelerate vertebrate protein evolution by liberating selective constraints. Whittle and Extavour analyse global rates of protein evolution and find no support for this hypothesis in vertebrates or invertebrates.

Luminescent materials are widely used for imaging and sensing because of their high sensitivity and rapid response. A strategy for modulating dual emission for radiometric sensing in a single component is now shown to enable tumour hypoxia imaging.

Regulators have identified around 30 cases of cancer linked to this blockbuster treatment. But is CAR T to blame? The hunt is on for answers.

The ovarian tumour protease (OTU) family of deubiquitinating enzymes (DUBs) are biochemically well-characterised and of therapeutic interest, however, only a few tool compounds exist to study their cellular function and therapeutic potential. Here, the authors present a chemoproteomics fragment screening platform for identifying DUB-specific hit matter, which combines activity-based protein profiling with high-throughput optimisation to enable rapid elaboration of initial fragment hits against OTU DUBs, and identify an enantioselective chloroacetamide-based covalent fragment for OTUD7B.

Researchers had high hopes for patient-derived xenografts. Now they are contending with limitations in the clinic and the lab.

The authors pooled resources to identify best practices and develop a new standardized protocol for estimating functional connectivity in rats with magnetic resonance imaging.

Tumours are subject to the same rules of natural selection as any other living thing. Clinicians are now putting that knowledge to use.

Many drugs unexpectedly influence the human gut microbiome, showed a recent study, prompting questions about toxicity assays, clinical implications and repurposing opportunities.