Search

The functions of the vast majority of brain-expressed spliced isoforms are unknown. Here the authors describe an isoform-resolution perturbation system coupled to a single cell transcriptomics read-out, and through this approach identify neuronal microexons that control autism-linked signatures underlying neuronal maturation and function

It has been proposed that language meaning is represented throughout the cerebral cortex in a distributed ‘semantic system’, but little is known about the details of this network; here, voxel-wise modelling of functional MRI data collected while subjects listened to natural stories is used to create a detailed atlas that maps representations of word meaning in the human brain.

Respiration enhances cerebrospinal fluid flow through mechanical and autonomic pathways. Inhale length and diaphragm motion influence its displacement and net flow, identifying a modifiable, noninvasive mechanism relevant to brain homeostasis.

In a phase 1b/2 trial, an off-the-shelf vaccine using gorilla adenoviral and modified vaccinia Ankara vectors with over 200 mutated peptides known to be present in persons with mismatch-repair-deficient tumors is safe and elicits neoantigen-specific T cells in individuals with Lynch syndrome.

Here, the authors show that methylphenidate alters brain organization by compressing the hierarchy between sensory and association areas. This dopamine-driven shift predicts improved attention, revealing how stimulants reorganize brain networks to enhance cognitive function.

Although the number of participants is important for phenotypic prediction accuracy in brain-wide association studies using functional MRI, scanning for at least 30 min offers the greatest cost effectiveness.

CLASSIC is a high-throughput genetic profiling platform that combines long- and short-read next-generation-sequencing modalities to quantitatively assess pools of constructs of arbitrary length containing diverse genetic part compositions.

One of three back-to-back papers to show dosage of BACH2 can modulate T cell differentiation and function and how we might apply this to enhance chimeric antigen receptor T cell therapies for cancer.

Rider, Grantham, Smith, Watson et al. integrate multiomic data from patients with psoriasis using dimensionality reduction and machine learning techniques. This approach identifies biological relationships between genetic background, clinical features and disease severity, providing insight into disease variability across individuals.

Stability and flexibility are important, if antagonistic, features of memory. Here the authors show that a class of inhibitory neurons regulate plasticity and therefore the stability of memory representations in novel contexts requiring flexibility.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

The molecular mechanisms underlying drug resistance in relapsed or refractory (rr) acute myeloid leukemia (AML) remain to be explored. Here, the use of bulk and single cell multi-omics and ex vivo drug profiling for 21 rrAML patients reveals mechanisms of resistance to the Bcl-2 inhibitor venetoclax and treatment vulnerabilities.

The authors timestamp the development of amyloid plaques in a mouse model of Alzheimer’s disease in order to examine how plaque age affects the surrounding brain tissue. This includes a growing loss of nearby synapses, an increase in toxicity, and an increase in structural aggregation.

Analysis of copy number alterations in 1,451 patient-derived xenografts (PDXs) and matched patient tumor samples shows strong conservation from patient tumors through late-passage PDXs and a lack of systematic copy number evolution driven by the mouse host.

The authors developed a deep learning-based model to estimate the brain age gap based on metabolic and structural imaging data in cognitively normal individuals and in patients with dementia. An older brain age was associated with Alzheimer’s disease biomarkers and was predictive of future cognitive decline.

MGAT1 is a glycosyltransferase critical for the synthesis and maturation of complex N-glycans. Here, the authors show that MGAT1 modulation of CD73 glycosylation and function regulates tumor immune response in triple-negative breast cancer.

Smargon et al. show that small nuclear RNAs can improve the cellular safety and efficacy of endogenous protein-mediated RNA base editing, enhancing nuclear RNA editing and the rescue of premature termination codon disease.

Phosphorylation and SUMOylation of the kainate receptor (KAR) subunit GluK2 have both individually been shown to regulate KAR surface expression. Here the authors find that KAR synaptic plasticity and transmission are regulated by the dynamic interaction of GluK2 phosphorylation and SUMOylation.

An approach that combines single-nucleus RNA sequencing and multiplexed perturbation identifies genes that enable the biosynthesis of direct precursors of the anti-cancer drug Taxol, whose current production involves a laborious extraction process from yew trees.

Resistance to first line treatment is a major hurdle in cancer treatment, that can be overcome with drug combinations. Here, the authors provide a large drug combination screen across cancer cell lines to benchmark crowdsourced methods and to computationally predict drug synergies.

An adaptive deep brain stimulation algorithm delivers targeted stimulation increases during movement using brain motor signals.

A population of TRAIL-positive astrocytes in glioblastoma contributes to an immunosuppressive tumour microenvironment and this mechanism can be targeted with an engineered oncolytic virus to improve outcomes.

The pilot phase of PigGTEx, re-analyzing 5,457 published RNA-seq samples, presents a pan-tissue catalog of molecular quantitative trait loci. Cross-species comparisons identify traits with shared genetic regulation in humans.

Several existing algorithms predict the methylation of DNA using Nanopore sequencing signals, but it is unclear how they compare in performance. Here, the authors benchmark the performance of several such tools, and propose METEORE, a consensus tool that improves prediction accuracy.

The mechanisms of recognition and response to emotional stimuli are not fully understood. Here, the authors reveal tuning to semantic and emotional image features within occipital temporal cortex that efficiently encodes information suited to guiding behavior.

Recurrence of meningiomas is unpredictable by current methods based on surgically removed specimens, and identification of patients likely to recur could inform treatment strategy. Here, the authors analysed DNA methylation in liquid biopsy specimens from meningioma patients to help classify recurrence risk noninvasively even before surgery.

Long-distance migration and dispersion is a common characteristic of nearly all classes of telencephalic GABAergic neurons, which diversify extensively after birth in the cortex and striatum, but show limited postnatal changes in the septum, preoptic area and pallidum.

Computational methods are becoming an increasingly important part of biological research. Using the Rosetta framework as an example, the authors demonstrate how community-driven development of computational methods can be done in a reproducible and reliable fashion.

Here, the authors develop pluripotent stem cell-derived kidney organoids by mimicking in vivo proximal differentiation, providing a model to study nephron development, injury responses, and a platform for therapeutic discovery.

Accurate protein synthesis depends on aminoacylated tRNAs, but their identities have been hard to measure. Here, authors present aa-tRNA-seq, a nanopore-based method that reveals the amino acid, sequence, and modification status of individual tRNAs at single-molecule resolution.

Immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS) infers B cell and T cell fractions from whole-genome sequencing data. Applied to the 100,000 Genomes Project datasets, circulating T cell fraction provides sex-dependent and prognostic insights in patients.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.

It is important to understand the correlates of protection against SARS-CoV-2 and its variants for future vaccine design. Here, the authors show that the complement system enhances the antibody-mediated neutralisation of SARS-CoV-2 via increased inhibition of virus-host interactions.

The mechanisms underlying the interplay between tumour cells and the microenvironment remain to be explored. Here, the authors report that the transcription factor FOXM1 epigenetically silences the DNA sensing pathway suppressing anti-tumour immunity and immune memory.

Hruska et al. suggest an architectural basis for NMDAR-dependent spine plasticity mediated by addition of unitary pre- and postsynaptic nanomodules that function as building blocks of synaptic organization and enable structural plasticity.

precisION discovers, localizes and quantifies protein modifications within complex proteoform assemblies through data-driven analysis of native top-down mass spectra.

How reduced blood flow plays a role in progressive white matter loss during aging and associated cognitive decline is unclear. Here the authors show that selective constriction and rarefaction of capillary–venous networks contribute to age-related hypoperfusion and white matter damage in mice.

Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.

GIANT, a genetically informed brain atlas, integrates genetic heritability with neuroanatomy. It shows strong neuroanatomical validity and surpasses traditional atlases in discovery power for brain imaging genomics.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Current view of the impact of A-site cation on the stability of perovskite materials and devices is derived from accelerated ageing tests at high temperature, which is beyond normal operation range. Here, the authors reveal the great impact of ageing condition on assessing the photothermal stability of mixed-cation perovskites using high-throughput robot system coupled with machine learning.

The clean-cooking transition in the Global South can support major improvements in public and environmental health and societal conditions. This study draws on survey data from greater than 7,000 households in Ghana to understand determinants of household fuel use through the transition and proposes a stage-based framework to support policy interventions.

By comparing neural responses to diverse visual stimuli measured with a standardized two-photon imaging pipeline, the authors reveal response specializations within the mouse visual cortex.

IL-27 promotes tumour control by preventing dysfunction and enhancing cytotoxicity of tumour-specific CD8⁺ T cells.

A machine learning approach shows that the downstream core promoter region (DPR) is widely used in human gene promoters, and that many promoters contain either a DPR or a TATA box, but not both.

The causes of ALS remain unclear with many proposed pathomechanisms. Here, the authors integrate iPSC-derived motor neuron and post-mortem datasets and identify a heightened DNA damage response accompanied by accumulation of somatic mutations in ALS.

End-stage kidney disease confers a high risk for severe COVID-19 infection. Using an at-risk group (end-stage kidney disease patients with COVID-19), authors using RNA-sequencing of immune cells and plasma proteomic profiling to investigate the host response to viral infection.

Ziegler et al. show that healthy young adults who used a meditation-inspired closed-loop app (MediTrain) for 6 weeks experienced gains in both sustained attention and working memory.