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Studying gene expression in admixed Black Americans, Benjamin et al. reveal genetic ancestry-linked differences impacting immune and vascular genes and potentially influencing neurological disease risk. These findings highlight the importance of considering ancestry in brain research.

Spikes of deep-layer ID2⁺Nkx2.1⁺ cortical neurons are anticorrelated with spiking of all principal cells and interneurons, prominently during down states of sleep, and shape the sequential firing of neurons at down–up transitions.

Circuit QED with strongly driven cavities is a powerful framework for quantum technologies, but often undesired effects on the qubit are introduced. Here, by using an external tone tailored to destructively interfere with the cavity field, the authors show how a transmon can be protected from these unwanted effects.

This study shows that brain connectivity changes in Huntington’s disease begin decades before symptoms, shifting from hyper- to hypoconnectivity, with links to specific neurotransmitter systems specially in granular and infragranular cortical layers.

Many fusion oncoproteins (FOs) form condensates, some form in the nucleus and regulate gene expression while others form in the cytoplasm and promote cell signaling. In this work, the authors report the analysis of physicochemical features to enable prediction of FO condensation behavior.

Dietary restriction promotes the expansion of effector T cells via ketone bodies, which enhances anti-tumour immunity and synergizes with immunotherapy in mice.

Drosophila larvae are able to perform visually-guided behaviours yet the molecular and circuit mechanisms for discriminating changes in light intensity are not known. Here, the authors report that ON versus OFF discrimination results from opposing cholinergic and glutamatergic mechanisms.

Several 17B-HSD13 variants have been identified as protective against NASH/MASH. However the protein’s endogenous function is unknown. Here authors describe sulfonamide-based inhibitors and synthetic substrates, then apply to multiple cellular systems revealing that the most prevalent IsoD variant maintains NAD-dependent catalytic activity.

Understanding how cells maintain tissues is challenging. Here, the authors present a single consistent quantitative approach to analyse cell proliferation and lineage tracing data, which shows a single proliferating cell population that maintains epidermal and esophageal epithelial homeostasis.

It is unclear whether trait trade-offs and optimality principles observed at the individual level scale up to the ecosystem level. Here, the authors show that plant trait coordination principles also predict patterns between community-level traits and ecosystem-scale processes.

The SARS-CoV-2 Nucleocapsid (N) protein serves multiple roles in the viral lifecycle. Phosphorylation toggles N between these roles by altering N’s conformation, its material properties when phase separated with RNA, and its membrane interactions.

Visual cognition compensates for small changes in an object’s appearance to ensure its perceived continuity. We show that in situations with multiple objects, context features like color, temporal or spatial position are used as anchors to selectively integrate corresponding objects over time.

Evan Eichler and colleagues use single-molecule molecular-inversion probes to sequence the coding and splicing regions of 208 candidate genes in more than 11,730 individuals with neurodevelopmental disorders. They report 91 genes with an excess of de novo or private disruptive mutations, identify 25 genes showing a bias for autism versus intellectual disability, and highlight a network associated with high-functioning autism.

Whether and how spindle-locked ripples contribute to memory consolidation by mediating memory reactivation in humans is not fully understood. The authors show that ripples in the human medial temporal lobe are associated with memory reactivation, establishing them as key factor in sleep-based memory re-processing.

Machine learning classifiers generated using chronic neural measurements in individuals with obsessive-compulsive disorder accurately predicted clinical status and deep brain stimulation response.

Vinculin binding to talin is a key event in focal adhesion dynamics; yet, how vinculin is activated to recruit actin remains unknown. Here, the authors use a multiscale approach to reveal that talin activates vinculin through an intricate allosteric mechanism tightly regulated by force.

Using high-speed atomic force microscopy, the authors reveal the polymerization mechanism of VIPP1 into ESCRT-III-like filaments that adopt spiral and polygonal supramolecular structures.

Phosphorylated peptide antigens are present on cancer cells, but their role in cancer immunity is unknown. Here, the authors describe a molecular mechanism, by which a tumor-specific phosphopeptide found in acute myeloid leukemia is recognized by the human immune T cells.

A novel personalized phage therapy strategy that selects phages for a predicted evolutionary trade-off may represent a viable alternative approach for the treatment of antimicrobial-resistant bacterial infections.

CAR-T cells have been found to be less effective as treatment for solid tumours. Here the authors, utilising B7H3 as an antigen, consider how changes in B7H3 binders lead to functional changes of CAR-T cells and differences in tumour outcomes in humanised mouse tumour models.

Cancer mutations in histone H3 cause genome instability, but the mechanisms remain to be elucidated. Here, the authors show in a plant model that the oncohistone H3.1K27M disrupts the TSK/TONSL-H3.1 DNA repair pathway.

The neural codes underlying working memory are not fully understood. Here the authors recorded neurons in the lateral prefrontal cortex of male macaque monkeys, during a working memory task, and identify activation sequences that encode target locations in the task.

This work presents CalicoST for inferring allele-specific copy numbers and reconstructing spatial tumor evolution by using spatial transcriptomics data.

Artificial intelligence (AI) system is known to improve dermatologists’ diagnostic accuracy for melanoma. This group applies the eye-tracking technology on dermatologists when diagnosing dermoscopic images of melanomas and reports improved balanced diagnostic accuracy when using an X(explainable) AI system comparing to the standard one.

Chimeric antigen receptor (CAR) T cells specific for an antigen, BCMA, have shown efficacy in controlling multiple myeloma in some patients, but responses vary. Here the authors show that, by over-expressing a granzyme B-NOXA fusion protein in anti-BCMA CAR T cells, cancer cells are rendered more susceptible to apoptosis induction and CAR T-mediated killing.

Spatial RNA sequencing is extended beyond poly-A transcripts to capture the full transcriptome.

This realist review shows that music therapy interventions must meet a person’s needs in the moment and be supported and integrated within the wider care environment to reduce distress and improve well-being for people with advanced dementia.

SARS-CoV-2 variants have accumulated multiple defining mutations within their spike glycoproteins. Here, the authors report a structural basis for broad neutralization of several variants by a heavy chain antibody fragment and provide a mutational analysis focusing on antibody evasion, receptor engagement, and spike protein structure.

Nagano et al. identify the third mitotic cohesin complex, STAG3–cohesin, which, with its unique biophysical properties, weakens insulation and rewires regulatory interactions of spermatogonial stem cells, shaping the male germline nucleome.

In experimental situations, random and sparse observations hinder understanding of the underlying complex dynamical system. The authors introduce a hybrid, transformer-based machine-learning framework to reconstruct the dynamics of new, unseen systems from sparse observations by training on a diverse set of synthetic systems.

This study investigates long-term trajectories of post-traumatic-stress-disorder symptoms of World Trade Center responders (n = 12,822), revealing highly variable symptom trajectories and 10% of responders experiencing persistence or worsening of symptoms after 20 years.

The application of electric fields >1 V/nm in solid state devices could provide access to unexplored phenomena, but it is currently difficult to implement. Here, the authors develop a double-sided ionic liquid gating technique to generate electric fields as large as 4 V/nm across few-layer WSe₂, leading to field-induced semiconductor-to-metal transitions.

Chronic brain infection and IL-1 exposure impair spatial memory by triggering DNA double-strand break signaling in hippocampal neurons. Blocking this pathway prevents memory deficits, suggesting new therapeutic prospects for various brain diseases.

Preliminary epidemiological evidence suggests that some non-cancer medications may affect breast cancer risk, recurrence, and survival. In this study, the authors utilized a nationwide database of breast cancer patients to estimate the association between frequently used drugs taken prior to diagnosis and breast cancer prognosis. And they identified 16 drugs associated with breast cancer outcomes.

Here, the authors unveiled a ‘super-silencer’ and its mechanisms of action. They revealed that a combined treatment of an enhancer of zeste homolog 2 inhibitor and a repressor element 1-silencing transcription factor inhibitor can disrupt super-silencers, potentially leading to cancer ablation.

Crop diversification could be important for food security. Here, using methods from network science, the authors find that a positive relationship between crop diversity and nutritional stability globally does not necessarily equate to improving nutritional stability in a given country.

In a new report, Benjamin Alman and his colleagues find that the morphogenic pathway activated by Hedgehog signaling is a key mediator of osteoarthritis, a condition that is marked by irreversible degeneration of the joints and with no current treatment. They also found that blockade of Hedgehog signaling prevented osteoarthritis in a mouse model, suggesting this pathway as a possible target to treat this devastating disease.

In this study, the concept of dynamic character displacement among interacting bacterial species from leaf-colonizing families was empirically tested using a proteomics approach. A phenotypic shift towards the utilization of alternative carbon sources was observed during coexistence, thereby minimizing niche overlap.

A genome-wide association study in ~3 million individuals identifies 3,952 independent variants associated with educational attainment. A polygenic index explains 12–16% of variance for this trait and contributes to risk prediction for ten diseases.

The neural systems which underlie the experience of anticipated threat under uncertainty are not well understood. Here, the authors find a whole-brain signature which specifically predicts anxious anticipation.

Current antimalarials often fail to target mature stage V gametocytes. To aid antimalarial drug discovery, the authors present a preclinical malaria transmission-blocking drug research platform, using engineered parasites, that facilitates the screening for gametocytocidal compounds in vitro and the evaluation of transmission-blocking drug activity in vivo.

This isoform-centric microglia genomic atlas includes 35,879 novel human microglia isoforms identified by long-read RNA sequencing. A multi-ancestry quantitative trait locus meta-analysis of known and novel isoforms in 555 samples from 391 donors finds associations with genetic risk loci in Alzheimer’s and Parkinson’s diseases.

Single-cell multi-omic analysis of 300,000 cells from 29 patients representing peripheral immune cells and colon mucosal immune, epithelial and mesenchymal cells reveals crosstalk between circulating and tissue-resident immune cells with epithelial cells in checkpoint inhibitor colitis and identifies potential therapeutic targets.

Classification of archaeal and bacterial viruses can be automated with an algorithm that identifies relationships on the basis of shared gene content.

Dietary changes can impact the microbial constitution of the gastrointestinal tract and modulate the local immune response. Here, the authors show supplementation using lysates of Methylococcus capsulatus Bath result in changes to the microbiota, modulate Treg populations and metabolic read outs in a dietary control murine model.

Hookworm infection remains a threat to public health where economic factors restrict treatment and lack of effective vaccination have limited successful therapeutic control which results in reinfection in endemic areas. Here the authors use a controlled human hookworm infection model and use high dimensional single cell profiling to show that plasmacytoid dendritic cells and regulatory T cells profiles that resemble those seen during natural infections in endemic areas.

Combined high-throughput protein engineering with machine learning to curate libraries of CRISPR genome-editing enzymes with distinct genome targeting properties is described.

Increasing the capacity of existing lines or adding new lines in power grids may, counterintuitively, reduce the system performance and promote blackouts. The authors propose an approach for prediction of edges that lower system performance and defining potential constrains for grid extensions.