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Ataluren restored SBDS protein synthesis in three patients with Shwachman-Diamond syndrome, improving bone marrow cellularity and pancreatic function without side effects, highlighting its potential as therapeutic option for this genetic disease.

UCHL5 is a deubiquitinating enzyme that cleaves Lys-48-linked polyubiquitin chains. Here, the authors discover through in-vivo CRISPR-Cas9 screens that Uchl5 is involved in immune evasion and modulation of extracellular matrix deposition in head and neck squamous cell carcinoma.

Precise separation of ions with similar valence and size is critical. Here, authors designed a selective membrane that precisely extract Li+ from Na+ and Ca²⁺ interferences. The high selectivity and permeability enable energy-efficient, precise, and chemical-free lithium extraction using the electrodialysis process.

Tian et al. show that RNA folding limits extensive base pairing among mRNAs in Drosophila germ granules. Instead, mRNAs interact via scattered bases exposed on the surface of folded RNAs, which may preserve proper gene function during development.

Hachem et al. show that AMPAR signaling drives the acute activation of ependymal-derived neural stem/progenitor cells after spinal cord injury and that this mechanism can be targeted therapeutically to harness the endogenous regenerative potential of the spinal cord.

Here the authors present a method to transform polygenic scores into disorder probabilities using only GWAS summary statistics, genotype data and a prior - no tuning sample is needed. The method enables individualized, well-calibrated predictions.

Genome-wide and targeted perturbation of DNA methylation at centromeres affects CENP-A positioning and centromere structure, resulting in aneuploidy and reduced cell viability.

Perception can occur in the absence of report. Here, the authors use intracranial recordings to show that sequential sampling of sensory evidence in the ventral visual cortex supports perception beyond report.

Spatial cell distribution within a tissue microenvironment is a rapidly advancing field. Here, authors assess three commercially available single-cell resolution spatial transcriptomics approaches (CosMx, MERFISH, and Xenium) to inform which technology outperforms for immune profiling of solid tumors using patient samples.

Bone marrow adipose tissue accounts for almost 10% of human fat mass, but its roles remain unclear. Here, Xu et al. identify more than 45 diseases linked to marrow adiposity in over 48,000 people, including causal roles in musculoskeletal disease.

Edge states of QSHIs hold promise for future technologies due to protection against backscattering. This work observes that intraband backscattering remains allowed for nonmonotonic edge bands, revealing critical aspects of edge state stability.

In angle-resolved photoemission spectra, nearly vertical energy-momentum dispersions, often termed waterfalls, can occur at high energies in materials including nickelates and cuprates. Using dynamical mean-field theory, the authors show that these features naturally emerge when a Hubbard band develops and splits off from the central quasiparticle band.

In 2022, mpox predominantly spread through sexual contact, necessitating updated prevention strategies. Here, the authors show that rectal challenge in male cynomolgus macaques with a 2022 clade IIb MPXV isolate mimics sexual transmission, and that vaccination with modified-vaccinia Ankara protects pre- but not post-exposure.

This study explores the relationship between telomere length and clonal hematopoiesis. Splicing factor and PPM1D gene mutations are more frequent in people with genetically predicted shorter telomere lengths, suggesting that these mutations protect against the consequences of telomere attrition.

The ribosomal decoding center monitors accurate translation of 3-base mRNA codons. Here, the authors use cryo-EM to show how one of the monitoring bases of the ribosome enables a frameshift-inducing tRNA to instead read a 2-base codon.

Doping is used in p-n junction devices to partially mitigate nonradiative recombination losses. Here, authors use phosphorus dopants to reduce charge carrier trapping and electronic band tails in polycrystalline CdSeTe, achieving improved ambipolar mobilities, fill factor and solar cell efficiency.

In this work, the authors investigate the activation mechanism of proprotein convertases (PC) based on the PC1/3-prodomain and the PC furin. They engineer a prodomain-nanobody fusion protein that effectively blocks propagation of a H7N7 bird flu virus.

Zeinert et al. provide cryo-EM structures of the E. coli Mg²⁺ importer MgtA: unexpectedly, this P-type ATPase is a dimer with an uncommon transmembrane ion-binding site and knotted N-terminus, which are functionally important features.

Surgical nerve injuries can cause significant morbidity, yet no approved fluorescent agents exist for visualization. Here, the authors show in a Phase I multi-site trial that bevonescein was safe, established optimal dosing and timing, and provided a fluorescence signal for intraoperative nerve identification.

Beck et al. develop a model where striosomes create a flexible “decision-space” that adapts to environmental context and internal state. It explains how we make choices and why decision-making varies between people, and in neuropsychiatric disorders.

Cells can regulate their mass density. Here, the authors demonstrate how eukaryotes establish and maintain a lower density in the nucleus than in the cytoplasm via pressure balance, and how deviations emerge during pathophysiological states like senescence.

Polygenic risk scores can help identify individuals at higher risk of type 2 diabetes. Here, the authors characterise a multi-ancestry score across nearly 900,000 people, showing that its predictive value depends on demographic and clinical context and extends to related traits and complications.

Cornelis Albers and colleagues identify NBEAL2 as the causative gene for gray platelet syndrome (GPS). Knockdown of this gene in zebrafish leads to spontaneous bleeding and defects in thrombocyte formation.

Perceptual abilities can be improved by training, up to certain limits. Martin et al. show that vagus nerve stimulation in mice boosts performance on an auditory task via cholinergic modulation, beyond the level achieved by training alone.

Here the authors apply ZooMS, radiocarbon, and stable isotope analyses to whale bones from the Bay of Biscay. They find that humans were utilizing the remains of at least five species of whales from 20,000 years ago, and that those whale communities may have resembled today’s arctic waters.

Allele-preferential transcription factor binding can influence pancreatic ductal adenocarcinoma risk loci function. Here, the authors show allele-specific JunB and JunD binding at chr1p36.33 and propose a role for KLHL17 in protein homeostasis by mitigating inflammation.

This study identified prevalent giant extrachromosomal elements from the human oral microbiome. The genetic and ecological analysis provides insight on the potential contribution of this element in adaptation against multiple oral environmental stressors.

GBA, a major gene for Parkinson’s disease and dementia with Lewy bodies, is associated with increased risk of developing dementia. Here, we demonstrate that GBA mutations in mice contribute to cognitive deficits through α-synuclein-independent mechanisms that impact synaptic vesicle endocytosis.

Xiangdong Fu and colleagues report characterization of a major rice grain yield QTL at the DEP1 locus.

The alveolar bone supports the tooth’s lifelong functionality. Here, the authors identify a tooth-specific mechanism of bone formation in which the Hedgehog–Foxf pathway regulates the alveolar bone osteoblast fates of DF progenitor cells.

A super-pangenome analysis incorporating 123 newly sequenced bryophyte genomes reveals that bryophytes exhibit a larger number of unique and lineage-specific gene families than vascular plants.

Geometric quantum gates—engineered evolution paths for qubit control—promise noise resilience but have shown limited fidelity in prior implementations in semiconductor quantum computation. Here the authors demonstrate high-fidelity single-qubit gates in a single-hole quantum dot in Ge, outperforming conventional dynamical gates.

The complex processes guiding mammalian cortical folding are incompletely understood. Here authors report that cortical folding was enhanced in mice by combining mutations affecting neuron adhesion and progenitor expansion, producing both sulci and gyri.

The tooth root is a critical component of the tooth. Here they identify root-forming CXCL12+ apical papilla progenitor cells that provide odontoblasts and cementoblasts in a Wnt-dependent manner, with plasticity to form alveolar bone osteoblasts during regeneration.

Reddy et al. used ancestral protein reconstruction, cryo-electron microscopy and functional assays to elucidate how a secondary active transporter evolved to harness the energy of sodium gradients to power the concentrative uptake of its substrate.

Alzheimer’s disease (AD) drug discovery has been hampered by patient heterogeneity, and the lack of sensitive tools for precise stratification. Here, the authors show an AI-guided model enhances patient stratification, improving outcomes and increasing efficiency in the AMARANTH trial.

The role of pathogenic mitochondrial DNA (mtDNA) mutation in cancer remains to be studied. Here the authors show that high mtDNA mutation burden in lung cancer models leads to increased glycolysis but limited de novo serine synthesis, rendering sensitivity to dietary serine and glycine deprivation.

A modeling approach to assess the global risk of Plasmodium falciparum histidine-rich protein 2 and 3 gene deletions identifies ten priority African countries for surveillance and could inform malaria control policies.

Spatial relationships between clustered proteins within synapses shape neurotransmission. Here, NMDA receptors are shown to align with only a subset of presynaptic release sites, suggesting a structural mechanism controls NMDAR-mediated synaptic transmission.

The EWSR1::FLI1 fusion protein is the oncogenic driver of Ewing sarcoma (EwS). Here, the authors find that EWSR1::FLI1 plays a non-canonical role in mRNA decay via interactions with the CCR4-NOT deadenylation complex and the RNA-binding protein HuR. This role uncovers a new therapeutic vulnerability of EwS to HuR inhibition.

Neel domain walls are typically stabilized by an interfacial Dzyaloshinskii-Moriya interaction, with a chirality that is fixed by the sample materials. Here, Song, Huang and coauthors demonstrate the existence of two bistable Néel domain wall states with opposite chiralities, and the switching between these via magnetic field pulses

The BabyScreen+ study offered genomic screening to 1,000 newborns in Australia, and showed that the approach is feasible and positively received by families, leading to molecular diagnoses in 1.6% of babies.

In people with severe brain injuries, stimulation restored consciousness by engaging a deep brain circuit for wakefulness—revealing a target that may also guide treatment in stroke and epilepsy.

The microbiomes associated with reef corals are complex and diverse. Here, the authors investigate fire coral clones naturally occurring in distinct habitats as a model system to disentangle the contribution of host genotype and environment on their microbiome, and predict genomic functions based on taxonomic profiles.

Both environmental factors and genetic factors influence human immunity. Albert and colleagues leverage data from the Milieu Intérieur Consortium to comprehensively describe the effects of lifestyle, environment and genetics on human innate and adaptive immunity.

How different cell types in primary motor cortex contribute to movement during learning and/or execution is not fully understood. Here authors show that corticothalamic neurons of the primary motor cortex are silent during movement and that this activity signature is critical for proficient movement generation.

Brain-wide recordings in mice reveal that prior expectations are distributed through recurrent loops across all levels of cortical and subcortical processing.

How metabolic reprogramming influences EMT during development has not been fully described. Here they explore how metabolism drives embryonic EMT and show that neural crest cells display molecular processes linking metabolic events with gene regulation during EMT.

Researchers from the NCI report how 14-3-3 proteins keep the Parkinson’s-associated kinase LRRK2 inactive, offering structural insights into disease mechanisms and highlighting strategies to stabilize LRRK2 for potential therapeutic benefit.