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Native top-down proteomics reveals epidermal growth factor receptor–estrogen receptor-alpha (EGFR–ER) signaling crosstalk in breast cancer cells and dissociation of nuclear transport factor 2 (NUTF2) dimers to modulate ER signaling and cell growth.

ProtAIDe-Dx is a deep joint-learning model that uses plasma proteomics to provide simultaneous probabilistic diagnoses across six conditions associated with aging.

A hexanucleotide repeat expansion of C9orf72 is translated to dipeptide repeat proteins in amyotrophic lateral sclerosis and frontotemporal dementia patients. Here the authors generate a C. elegans model of C9orf72-mediated ALS/FTD and show that translation initiation factor eIF2D regulates the dipeptide repeat protein expression.

The functional impact of most missense variants remains unknown. Here the authors perform deep mutational scanning of the tumor suppressor SMARCB1 and find missense mutations that retain detectable protein expression but disrupt function similar to protein-null mutations

Cue-evoked striatal dopamine release in mice encodes bidirectional trajectory errors, spatially and temporally separated from value coding, reflecting the relationship between the speed and direction of ongoing movement relative to optimal goal trajectories.

Analysis of nuclear and mitochondrial genomes from archaeological canid remains found across Europe and Anatolia shows that a genetically homogeneous dog population was already widely distributed across the region by 15,000 years ago.

Drugs that rescue function of episodic ataxia 1 (EA1) mutant potassium channels are lacking. Here, Manville et al identify and describe the molecular basis for Native American botanical ataxia remedies that directly rescue EA1 mutant channels.

Decreased brain volumes and increased NfL levels can be observed earlier than disease diagnosis in short-tandem-repeat-associated neurological diseases.

The authors present a comprehensive plant-specific modelling framework for CRISPR gene drives: dormant seed banks can slow spread and require larger releases but can also ease weed elimination and limit unintended spread to nearby populations.

A brain–machine interface is used in monkeys to investigate the biophysical underpinnings of cortical high gamma-band activity, a signal that is often studied in the context of many brain functions.

Nuclear protein homeostasis relies on proteasome import into the nucleus. Here the authors identify how assembled human proteasomes are transported across the nuclear pore complex and reveal a mechanism enabling the large complex to bypass pore size limitations.

A technique called condense-seq has been developed to measure nucleosome condensability and used to show that mononucleosomes contain sufficient information to condense into large-scale compartments without requiring any external factors.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

Over five years, implementation of the NHS England Lung Cancer Screening Programme achieved high early-stage detection rates and demonstrated that the programme is both feasible and scalable for reaching high-risk and underserved populations.

Genetic analyses in more than 15,000 individuals from across the Americas, including individuals with autism and family members, define the genetic landscape of autism in Latin American populations and identify significant overlap with other ancestries.

Genome-wide analysis shows European dogs existed by 14,200 years ago, were already genetically distinct, received less Neolithic Southwest Asian admixture than humans did and contributed substantially to later European dogs.

ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

Neuroinflammation triggers DNA damage and subsequent parthanatos-mediated neuron death. Inhibiting parthanatos in a mouse model of autoimmune inflammation is neuroprotective and reduces disease-associated paralysis.

Individual supratentorial ependymoma tumour subgroups have two distinct progenitor-like cell states—neuroepithelial-like and embryonic-like—that are reminiscent of early human brain development and diverge in the extent of their neuronal or ependymal differentiation.

Polyamides (PAs) or nylons are types of plastics with wide applications, but due to their accumulation in the environment, strategies for their deconstruction are of interest. Here, the authors screen 40 potential nylon-hydrolyzing enzymes (nylonases) using a mass spectrometry-based approach and identify a thermostabilized N-terminal nucleophile hydrolase as the most promising for further development, as well as crucial targets for progressing PA6 enzymatic depolymerization.

Parsimonious deep neural network models can be used for prediction of visual neuron responses.

The ~200-Myr-old star TOI-2076 hosts a young four-planet system, the orbits and atmospheres of which are still evolving, showing signs of early dynamical reshaping and atmospheric sculpting and offering a rare glimpse of how planetary systems form and transform in their youth.

A pangenome reference for the phenotypically diverse crop sorghum aims to help accelerate future efforts to breed crops that are better adapted to changing environments.

Hexanucleotide GGGGCC repeat expansion in C9ORF72 is the most frequent cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here the authors show that (GGGGCC) _n translation can initiate without a 5′-cap, and this cap-independent translation is upregulated by stress mediated through eIF2α phosphorylation.

In a large UK-based primary care randomized trial, immediate artificial intelligence (AI)-driven prioritization of chest X-rays did not significantly shorten time to computed tomography or lung cancer diagnosis versus standard workflow, suggesting that AI-based prioritization alone is unlikely to accelerate the lung cancer diagnostic pathway.

A candidate-based genetic screen in Drosophila expressing 30 G₄C₂-repeat-containing RNAs finds that RanGAP, a key regulator of nucleocytoplasmic transport, is a potent suppressor of neurodegeneration; the defects caused by the G₄C₂ repeat expansions can be rescued with antisense oligonucleotides or small molecules targeting the G-quadruplexes.

Liquid-cell transmission electron microscopy is used to investigate the network structure of cellulosic gels. The formation of nano- and microscale fibrillar bundles is observed, providing insight into structure–property relationships in hydrogels.

Brief ultrasound to human frontal eye fields, but not motor cortex, rapidly biases eye movement contralaterally in a perceptual choice task. The size of this effect scales with individual baseline FEF inhibitory tone.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Nuclear pore complexes control selective transport between the nucleus and cytoplasm. Here, the authors show how FG-Nups and transport receptors form a dynamic interface that enables selective and efficient transport.

JWST imaged three of the gas giants orbiting the star HR 8799 to study their atmospheres. The uniform enrichment of heavy elements, including sulfur, indicates that they formed like Jupiter and Saturn by accreting a lot of icy and rocky solids.

The mitochondrial pathway of apoptosis requires coordinated protein–lipid signals. Here, Gelles et al. show that a BAX lipid-binding cavity for 2-trans-hexadecenal cooperates with BIM to allosterically activate BAX prior to membrane insertion.

Carrington and colleagues explore how HLA class I signal peptide polymorphism influences NK cell functionality. They derive a genetically informed SP score metric that predicts CD94/NKG2A–HLA-E binding strength, correlates with human CD56^bright NK responsiveness and associates with disease risk.

KRAS mutations are keenly associated with pancreatic ductal adenocarcinoma and represent a potential therapeutic target. Here the authors present the findings from a phase I clinical trial testing pooled KRAS mutant peptides in combination with immune checkpoint blockade in patients with resected pancreatic ductal adenocarcinoma.

Using 63 globally distributed grassland and shrubland sites from the International Drought Experiment, this study identified plant traits linked to drought resistance after 1 year of extreme drought across growth forms, lifespans and climate.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

This study shows how the bacterial retron Eco2 defends against viruses. Phage nucleases trigger activation of Eco2, which cuts RNAs, shuts down protein production and stops phage replication.

Oceans provide essential ecosystem services to human society, yet the climate impacts on blue capital have long been ignored. Incorporating the latest works on ocean science and economics, researchers show that accounting for the potential damage would almost double the social cost of carbon estimation.

Magnon transport is confined to a plane by sandwiching BiFeO₃ between layers of non-polar antiferromagnetic LaFeO₃, resulting in efficient magnon transport and a higher voltage output through spin–charge conversion that can be controlled using electric fields. These results have implications for electric-field-controlled spin-based memory and logic elements.

In scenarios involving 1,000 acute-pain clinical vignettes, varied across 34 socio-demographic features, a panel of ten large language models is found to provide inconsistent recommendations, which also present disparities with respect to marginalized populations.

Soft and conducting organic materials are promising for electronic devices, though their nanostructures are not fully understood, due to the lack of high resolution real spacing imaging of these complex systems. Here the authors use cryogenic transmission electron microscopy methods to investigate the morphology of PEDOT:PSS in the presence of additives and upon hydration.

An online experiment compared 12 brief online interventions for depression. Most improved mental health immediately, but these gains decreased over time, with only two interventions significantly reducing depression 4 weeks later.

Hexanucleotide repeat expansion in the intron 1 of the C9ORF72 gene can cause amyotrophic lateral sclerosis (ALS) and frontal temporal dementia (FTD). Here the authors use single molecule imaging to show nuclear export and translation of circular repeat-containing C9ORF72 intronic RNA.

Although defects in nucleocytoplasmic transport (NCT) may be central to the pathogenesis of ALS, the molecular mechanisms modulating the nuclear pore function are still largely unknown. Here, authors show that genetic and pharmacological modulation of actin polymerization disrupts nuclear pore integrity and can be targeted to rescue nuclear pore instability and dysfunction caused by mutant PFN1 as well as by C9ORF72 repeat expansion