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Analysis of shared chromosomal segments is applied to identify distantly related, previously undiagnosed carriers of a rare KCNE1 variant. The carriers are shown to have the Long QT Syndrome phenotype with incomplete penetrance.

The first controlled human infection model of cutaneous leishmaniasis transmitted by sand flies enables assessment of immune responses and parasitism in infected participants that can inform future vaccine and therapeutic development.

Arbuscular mycorrhizal fungi help plants to overcome soil nutrient limitations. To promote symbiosis these fungi use effector proteins. The authors show that the SP7 effector family modulates host alternative splicing, impacting host development.

Contacts between mitochondria and endoplasmatic reticulum (ER), and the transfer of calcium between them, have an important role in the regulation of cellular phenotypes, including senescence. Here the authors show that ITPR2 deficient mice display improved aging, associated with a decreased number of contacts between the mitochondria and the ER.

Mycobacterium tuberculosis infection remains a global health crisis. Here researchers characterise the alveolar macrophage subsets in a murine model of BCG vaccination in mice and link increases of CD38+ macrophages with restriction of bacterial growth.

Technical challenges have previously hindered the detailed study of in vivo senescent cells. Here, the authors deeply characterize senescent skeletal cells across murine aging, establishing CD24 as a marker of osteolineage cells cleared by senolytics.

Malaria mosquitoes use their ears to detect the flight tones of mating partners in the swarm as part of the courtship ritual. Here, the authors describe the auditory role of octopamine as a modulator of auditory plasticity in malaria mosquitoes and identify the main receptors involved in this process.

During aging, the ability of skeletal muscle to repair itself declines, in part due to a decrease in muscle stem cells. Here, the authors report that muscle stem cells that accumulate mitochondrial damage fuse with existing muscle fibers in a manner that depends on the induction of Scinderin.

OPA1 regulates the formation of the distinct mitochondrial morphology observed in T helper 17 cells, which influences cytokine expression via LKB1.

The neurotransmitter dopamine is known to regulate learning and decision-making. Here, the authors show that pharmacologically enhancing dopamine levels influences the regulation of speed and accuracy during reward learning.

The whisking oscillator—consisting of parvalbumin-expressing inhibitory neurons located in the vibrissa intermediate reticular nucleus—in mice is an all-inhibitory network and recurrent synaptic inhibition has a key role in its rhythmogenesis.

Post-stroke walking impairment is a significant public health concern. Here, the authors perform an interventional, randomized controlled trial evaluating the efficacy and safety of InTandem™, an autonomous neurorehabilitation system utilizing auditory-motor entrainment to improve walking after stroke.

Investigators present findings from a double-blind randomized controlled trial of personalized stimulation of the left dorsolateral prefrontal cortex using transcranial magnetic stimulation to increase hypnotizability in a sample of patients with fibromyalgia syndrome.

A global gauge-corrected monthly river flow and storage dataset suggests that residence time is a key driver of water storage and variability and indicates substantial freshwater discharge to the ocean from the Maritime Continent.

A neural epigenetic signature detectable via plasma analyses is prognostic in patients with glioblastoma, resembling an oligodendrocyte-progenitor- and neuronal-progenitor-cell-like state and showing increased neuro-to-glioma synapse formation.

Synaptic dysfunction is hypothesised to play a key role in schizophrenia pathogenesis. Here, using [¹¹C]UCB-J PET, the authors show for the first time in vivo that levels of the synaptic marker protein SV2A are reduced in schizophrenia and unaffected by antipsychotic treatment in a rat model.

Trajectory-coding neurons in the hippocampus convey important information for performing memory tasks. Here, Kinsky et al. track long-term neural activity in the hippocampus to find that trajectory-coding emerges rapidly and remains stable across long time-scales.

Cerebral adrenoleukodystrophy (CALD) is a demyelinating disease caused by loss of ABCD1 gene function. Here the authors investigate white matter structural and microvascular changes in boys with CALD that received gene therapy with autologous hematopoietic stem-cells.

Inflammatory monocytes are identified as important players in T cell restimulation in the tumour microenvironment.

Tyrosine kinase 2 (TYK2) critically regulates tau levels and aggregation by phosphorylating tau’s tyrosine 29. Partial inhibition of TYK2 mitigates tau pathologies in cells and mice, highlighting TYK2 as a potential therapeutic target for Alzheimer’s disease and other tauopathies.

A subpopulation of astrocytes selectively expresses synaptic-like glutamate-release machinery, actively secretes the transmitter and is localized to discrete sites in the hippocampus.

Inclusion body myositis (IBM) is a progressive inflammatory muscle disease of unknown cause, prevalent in older adults. Through spatial and single nuclear profiling, the authors identify a selective type 2 myofiber pathology in IBM, linked to genomic stress and denervation.

Despite decades of use in clinical care, only half of individuals who receive continuous renal replacement therapy (CRRT) benefit, and no consensus exists around who should be placed on CRRT. Here, the authors use electronic health record data from multiple institutions to improve prediction of CRRT response before initiating treatment

IL-11 is identified as a key regulator of ERK–AMPK–mTORC1 signalling, metabolism, inflammation and age-related disease and lifespan in mouse and human.

Sakata et al. performed a prospective personalized mechanistic computational (digital twin) study focused on characterizing the arrhythmogenic properties of the atrial fibrotic substrate in patients with persistent atrial fibrillation, and they introduce here a novel mechanism-oriented strategy for optimal ablation.

Self-tolerance is established during B cell development but the contribution of clonal deletion, receptor editing, anergy and apoptosis is debated. Here we show that although apoptosis does occur in a high proportion of transitional B cells after exiting the bone marrow, the reactivity of apoptotic B cells does not differ from that of viable cells, which argues against apoptosis as major mechanism to eliminate self-reactive and polyreactive clones.

Faecal carbon:nitrogen measurements and manipulation of nitrogen availability via diet and host secretions in a murine model suggest that intestinal nitrogen limitation occurs due to host absorption and microbial use, leading to benefits for specific taxa.

Serotonin has a role in ependymoma tumorigenesis through modifying histones and thereby regulating key transcription factors and activating specific oncogenic transcriptional networks in brain cells.

Depression is associated with dysregulated circadian rhythms. Here, the authors show a critical role for mPFC molecular clock in regulating depression-like behavior and therapeutic potential of clock modulators influencing glutamatergic plasticity.

In-depth characterization of adeno-associated virus (AAV)-mediated CRISPR delivery is still lacking. Here, the authors show high levels of integration into Cas9-induced double-strand breaks (DSBs) in therapeutically relevant genes in vivo.

Interleukin (IL)-1α is a critical inflammatory cytokine and yet its intracellular role is poorly understood. Here, the authors use proximity labelling of pro-IL-1α and assess its interactome, and dissect the presence and impact on a conserved nuclear interaction and its impact on the immunobiology and evolutionary convergence/divergence between species.

A study of genetic associations identifies 46 new loci associated with alcohol consumption. By assessing their function and potential pleiotropy, the authors suggest genetic mechanisms that are shared with neuropsychiatric disorders, including schizophrenia.

Soft tissue trauma can result in aberrant osteochondral differentiation of local mesenchymal progenitor cells. Here the authors show that, in mice, soft tissue trauma results in NGF expression by perivascular cells, which leads to axonal invasion and drives abnormal osteochondral differentiation, and show that this process can be prevented by inhibition of NGF signaling.

Using viral sequence data, individuals with persistent SARS-CoV-2 infections were identified, and had higher odds of self-reporting long COVID, in a large community surveillance study.

The potential of evinacumab, a monoclonal antibody targeting angiopoietin-like 3, for reducing triglyceride levels was tested in patients with severe hypertriglyceridemia due to differing genetic etiologies.

The Huntington's disease (HD) induced pluripotent stem cell (iPSC) consortium describe the combined use of differentiated patient-derived iPSCs and systems biology to discover underlying mechanisms in HD. They identify neurodevelopmental deficits in HD cells that can be corrected in cells and in vivo with a small molecule.

We describe a human DNA methylome atlas based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis of cell-type-specific markers and providing an essential resource for studies of gene regulation and for deconvolution of cell mixtures and liquid biopsies.

Resident microglia in the central nervous system are identified as the specific macrophage population that regulates myelin growth and integrity.