Search

N¹-Methylpseudouridine enhances the translation of synthetic mRNAs, independently of innate immunity.

The anterior cingulate cortex encodes affective pain behaviours modulated by opioids; targeting opioid-sensitive neurons through a new chemogenetic gene therapy replicates the analgesic effects of morphine, providing precise chronic pain relief without affecting sensory detection.

Neural mechanism underlying behavioural flexibility is not fully understood. Here authors study decision-making of macaques in a reversal task. They identify two complementary cognitive processes. Distinct neural patterns link these processes to the dorsomedial prefrontal cortex, thalamus, and hippocampus.

A suite of TadA-derived cytosine base editors was optimized to improve efficiency, reduce sequence bias, expand PAM compatibility and minimize artefacts, enabling precise genetic interrogation of variants of uncertain significance (VUS) in zebrafish.

A synthesis of respirometry data, telemetry studies, long-term population monitoring, and in situ predator-prey experiments reveals that aerobic scope can circumstantially both limit and facilitate the fitness of imperiled Chinook salmon populations.

Affinity-proteomics platforms often yield poorly correlated measurements. Here, the authors show that protein-altering variants drive a portion of inter-platform inconsistency and that accounting for genetic variants can improve concordance of protein measures and phenotypic associations across ancestries.

The 4D Nucleome Project demonstrates the use of genomic assays and computational methods to measure genome folding and then predict genomic structure from DNA sequence, facilitating the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.

A platform using matched patient-derived lung tumouroids and healthy lung organoids enables accurate examination of patient responses to CAR T therapy and offers a faithful framework for improved CAR T design.

Here the authors present NCATS-SM0225, a small molecule that inhibits ERAD and selectively kills cancer cells by binding VDACs, disrupting calcium homeostasis, and triggering the PERK-STIM1 pathway to degrade ERAD regulators.

In a randomized controlled trial that included 97 participants, 69% patients with Crohn’s disease (CD) allocated to a fasting-mimicking diet (FMD) achieved clinical response, and over 60% reached remission, outperforming the control group. The FMD also reduced markers of intestinal inflammation, suggesting this dietary intervention could serve as adjunctive treatment for CD.

Spatially resolved gene expression during barley development was done by integrating an scRNA-seq dataset from cells with unknown position with spatial transcriptomics. This dataset is publicly available through the online web-based BARVISTA application.

In a multicenter, randomized trial of patients with atrial fibrillation and a low risk of thromboembolic events, treatment with the anticoagulant rivaroxaban showed no benefit in reducing cognitive decline, stroke or transient ischemic attack when compared to placebo.

Fermionic currents of opposing chirality can be spatially filtered without the need for a magnetic field using the quantum geometry of topological bands in single-crystal PdGa.

The enzyme PCMT1 was found to install a C-terminal cyclic imide modification on proteins that marks them for degradation by CRBN, uncovering a conserved protein turnover pathway with implications in metabolism and neurological function.

Analysis of behavioral data often involves tracking animal keypoints in video and motion capture recordings. DISK imputes missing keypoints, thereby improving downstream analyses.

Pathogenic variants in KIF1A give rise to KIF1A-associated neurodegenerative disorder (KAND). Here, the authors use antisense oligonucleotides targeting common polymorphisms to knock down pathogenic KIF1A expression in patient-derived stem cells.

Bessler et al. developed a human organoid model for H3.3K27M-altered diffuse midline glioma that recapitulates key tumor features and demonstrated its utility for modeling CAR T cell and microglia functions.

Here the authors show that tissue-resident memory and exhausted T cells in tumors are distinct populations that are shaped by relative presence or absence of TCR signals, suggesting that a tailored therapeutic strategy is needed to target each subset.

A 15-year prospective cohort study found that during times of social unrest in Hong Kong, people experienced more conflicts with family and friends and this coincided with the use of social media—these factors were also associated with higher levels of depression.

Vibrio cholerae O1 outbreak strains are classified as Ogawa or Inaba serotypes, but the impact of serotype on pathogenicity is understudied. Here, the authors show that O1 antigen methylation in Ogawa strains promotes colonization and infectivity.

Hole spin qubits in germanium have seen significant advancements, though improving control and noise resilience remains a key challenge. Here, the authors realize a dressed singlet-triplet qubit in germanium, achieving frequency-modulated high-fidelity control and a tenfold increase in coherence time.

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.

Lipid nanoparticle based mRNA vaccines are known to induce robust CD4 + T cell responses. Here the authors establish a role of endogenously derived antigen processing in the optimal priming of CD4 + T cell responses to mRNA lipid nanoparticle vaccines.

Multimodal fusion of digital pathology and transcriptomics can improve cancer diagnosis, but remains impractical in clinical settings. Here, the authors develop a crossmodal generative model, PathGen, to synthesise transcriptomic data from histopathology slides, and show how the combination of these multimodal data improves cancer diagnosis and prognosis prediction.

When doubly-degenerate band crossings known as Kramers nodal lines intersect the Fermi level, they form exotic three-dimensional Fermi surfaces composed of massless Dirac fermions. Here, the authors present evidence that the 3R polytypes of TaS₂ and NbS₂ are Kramers nodal line metals with open octdong and spindle-torus Fermi surfaces, respectively.

This study reveals that anti-NS1 IgA antibodies in plasma, induced by prior Zika virus infection, activate neutrophils, underlying severe dengue disease upon a subsequent DENV2 infection, uncovering a pathogenic mechanism relevant for vaccines and therapeutics.

A generative artificial intelligence-powered method enables de novo design of highly active enzymes based on information about the geometry of residues in the active site, without requiring protein backbone or sequence information.

Using ecological momentary assessment and multilevel time-series models, we quantify loneliness inertia and its links to perceived social threat and social behavior, identifying dynamic patterns that help explain the persistence of chronic loneliness.

A detailed spatiotemporal roadmap of the human female and male reproductive tracts during key periods of sexual differentiation provides new cellular and molecular insights into how early axial gradients lead to specific cell lineages and tissue structures.

In statistical physics, systems usually become disordered at high temperatures, but some exhibit entropic order when heated, where one type of ordering enables greater fluctuations in another. Here the authors show how this type of order can persist to arbitrarily high temperature in simple classical and quantum many-body models.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

A clinical cohort-based biomarker study in patients with metastatic renal cell carcinoma demonstrates that blood levels of soluble mucosal addressin cell adhesion molecule-1 are prognostic for survival in patients treated with tyrosine kinase inhibitors and immune checkpoint inhibitors and may serve as a surrogate marker for gut dysbiosis based on integrated data from three clinical trials.

The inter-system crossing induced by selenium may undesirably enhance formation of triplet excitons in non-fullerene acceptors, leading to increased non-radiative losses. Here, the authors introduce achiral N-alkyl substituents, achieving maximum efficiency of 20.4% for ternary organic solar cells.

The authors study pseudogap in electron-doped cuprates by computing the fermionic self energy beyond Eliashberg approximation. They show that recent experiments are consistent with the idea that pseudogap behavior is caused by thermal antiferromagnetic fluctuations with no Fermi-surface reconstruction.

During development of eutherian females, one of the X-chromosomes is silenced. Here, authors show that alleles on the inactive X-chromosome are dynamically expressed along neural differentiation enhancing resilience of female neural tissue.

The B1.23.2 antibody binds HLA-B*44:05 at a site that overlaps the killer Ig-like receptor binding site. It blocks inhibitory receptor interactions, leads to NK cell activation and suppresses tumor growth in a humanized mouse model.

Tree buds integrate cold and warm cues to control dormancy release. Extended warm periods block plasmodesmata opening by repressing Flowering Locus T and GA pathways in buds. This mechanism ensures robust temporal regulation of dormancy release.

Base editor off-target effects are profiled with high precision in a tailored approach.

Centennial-scale variations in methane carbon isotope ratios are attributed to changes in pyrogenic and biogenic sources that can be correlated with anthropogenic activities, such as varying levels of biomass burning during the period of the Roman empire and the Han dynasty, and changes in natural climate variability.

FACED 2.0 builds on and expands the capabilities of the free-space angular-chirp-enhanced delay microscopy approach. Its high speed, large field of view and volumetric coverage enable two-photon voltage imaging of hundreds of neurons or calcium imaging of thousands of neurons in the mouse or zebrafish brain.

The existing ENCODE registry of candidate human and mouse cis-regulatory elements is expanded with the addition of new ENCODE data, integrating new functional data as well as new cell and tissue types.

The authors report an enhancement of the superconducting onset temperature in nanometer-thin YBa₂Cu₃O₇-δ films grown on substrates with nanofaceted surfaces. They theoretically show that the enhancement is mainly driven by electronic nematicity and unidirectional charge density waves, and further suggest that the nanofacets themselves may promote these effects.

Glioblastoma is characterised by high levels of intratumoural heterogeneity and plasticity, hindering treatment. Here, the authors develop an analytical framework, scFOCAL, to predict the sensitivity of glioblastoma cell subpopulations to therapies based on reversal of disease transcriptional signatures to identify synergistic therapeutic combinations.

Distinct neuron subtypes compartmentalize specific functions by differentially localizing and translating specific RNAs. This work identifies dynamic subtype- and stage-specific growth cone molecular machinery during neocortical circuit development.

Myeloid derived suppressor cells (MDSC) use different metabolic mechanisms to adapt to the tumour microenvironment. Here the authors show that 6-phosphogluconate dehydrogenase (6PGD) is important for MSDC function and that blockade of 6PGD impaired MDSC function and suppresses tumour growth leading to metabolic and functional changes in the MDSC and a more pro-inflammatory phenotype.