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Whole-genome alignment of 239 primate species reveals noncoding regulatory elements that are under selective constraint in primates but not in other placental mammals, that are enriched for variants that affect human gene expression and complex traits in diseases.

Song et al. inferred that stridulatory wings and tibial ears co-evolved in a sexual context among crickets, katydids, and their allies, while abdominal ears evolved first in a non-sexual context in grasshoppers, and were later co-opted for courtship. They found little evidence that the evolution of these organs increased lineage diversification.

The mechanisms regulating the balance between proliferation and differentiation in medulloblastomas with extensive nodularity (MBEN) remain poorly understood. Here, single cell multi-omics and spatial analysis characterises the spatial tissue organisation of MBEN in the context of the developmental trajectory.

Empirically based models of disease progression in familial frontotemporal dementia reveal the relative ordering of clinical, neuroimaging, and fluid biomarker changes and facilitate novel clinical trial designs

Two below-threshold surface code memories on superconducting processors markedly reduce logical error rates, achieving high efficiency and real-time decoding, indicating potential for practical large-scale fault-tolerant quantum algorithms.

Authors utilise a multi-omics approach for the ecophysiological characterization of a taurine-respiring mouse gut bacterium.

A hybrid CRISPR–Cas9 variant is able to specifically and efficiently target a larger proportion of the genome.

Genomic analyses of large population-based cohorts uncover the genetic determinants of perivascular space burden, an MRI marker of cerebral small vessel disease, across the lifespan, and reveal potential pathways implicated in the etiology of stroke and dementia.

Physical realizations of qubits are often vulnerable to leakage errors, where the system ends up outside the basis used to store quantum information. A leakage removal protocol can suppress the impact of leakage on quantum error-correcting codes.

Sarcomatoid and rhabdoid tumours are highly aggressive forms of renal cell carcinoma that are also responsive to immunotherapy. In this study, the authors perform a comprehensive molecular characterization of these tumours discovering an enrichment of specific alterations and an inflamed phenotype.

Two ‘outrigger’ telescopes were added to CHIME, leading to the localization at detection of FRB 20210603A. The burst originated from deep within the star-forming disk of its host galaxy.

The stromal microenvironment plays a key role in the expansion of chronic lymphocytic leukemia. Here, the authors use the Eµ-TCL1 mouse model to show that leukemic B-cells induce the activation of retinoic acid synthesis in stromal cells of the lymphoid microenvironment, and that impacting on retinoic acid signalling via diet or chemical inhibition prolonged survival by preventing leukemia dissemination and accumulation in lymphoid tissues.

Cannabinoid-induced feeding signals are shown to enhance pro-opiomelanocortin (POMC) neuronal activity in mice, causing an enhancement of β-endorphin release, which is crucial in causing this cannabinoid-induced response; these results uncover an overlooked role of hypothalamic POMC neurons in the promotion of feeding by cannabinoids.

Insufficient AHR activation has been suggested in SLE, and augmenting AHR activation therapeutically may prevent CXCL13⁺ T_PH/T_FH differentiation and the subsequent recruitment of B cells and formation of lymphoid aggregates in inflamed tissues.

Here the authors show in freely moving human participants that deep brain oscillations in the medial temporal lobe flexibly encode both memory and spatial information, depending on the current cognitive task demands.

Using various mouse models, human plaque data and isolated B cells combined with state-of-the-art imaging and transcriptomic analysis, the authors show that the G-protein-coupled orphan receptor GPR55 regulates B cell activation and plasma cell differentiation during hypercholesterolemia, which crucially affects atherosclerosis.

Here, de Sá et al. show that Gasdermin-D is transiently activated in Leishmania-infected macrophages and promotes NLRP3 inflammasome activation, but not cell death. Gasdermin-D is cleaved into a noncanonical fragment, indicating that Leishmania subverts Gasdermin-D-mediated host response to establish leishmaniasis.

Rasheed et al. show that dysregulation of lipid metabolism uniquely affects splenic endothelial cells of the hematopoietic niche, which promotes extramedullary myelopoiesis and contributes to plaque accumulation during atherosclerosis.

Using molecular dynamics simulations and functional assays, authors track the structural changes in heterotrimeric G proteins in response to receptor coupling that lead to the ejection of GDP, the rate-limiting step during G-protein activation.

Risk for renal cell carcinoma (RCC) is higher when there are first-degree family members with the disease. Here, Scelo and colleagues perform a genome-wide association meta-analysis and new genome-wide scan to identify seven new loci with significant RCC association.

John Chambers, Jaspal Kooner, Pim van der Harst, Shyong Tai, Paul Elliott, Jiang He, Norihiro Kato and colleagues performed a genome-wide association study of blood pressure phenotypes in individuals of European, East Asian and South Asian ancestry. They find trait-associated SNPs at 12 loci, some of which are associated with methylation at nearby CpG sites.

Tau pathology drives neuronal dysfunction in 4- repeat tauopathies. Here, the authors combine tau-PET, resting-state fMRI and histopathology data, to show that brain connectivity is associated with tau deposition patterns in 4-repeat tauopathies.

The precise regulatory mechanisms controlling ciliary Hedgehog signaling remain incomplete. Here, the authors use ciliary proteomics to reveal that Numb facilitates the endocytosis of the receptor Ptch1 from the ciliary pocket, thereby enabling activation of Hedgehog signaling.

Chapeau et al. develop a nonallosteric inhibitor of the interaction between YAP and all four TEAD proteins. Treatment with the inhibitor, either as monotherapy or in combination with other treatment modalities, leads to induction of cell death in several in vivo cancer models.

Cerebral malaria infection can provoke fatal neuroinflammation. Gros and colleagues identify an ubiquitin-modification axis that exacerbates neuroinflammation and that involves TRIM25 and USP15, which jointly promote type I interferon production.

Combining analysis of host proteome and transcriptome perturbations induced by tumour virus proteins with ongoing genome-wide studies of cancer facilitates the prioritization of cancer genes.

Cajal-Retzius neurons number drastically decreases during postnatal life. Here, authors show that their programmed death is required for the construction of functional hippocampal circuits and memory with aberrant survival leading to gamma rhythmopathies and susceptibility to seizures.

Topical microbicide combined with vaccine effectively prevents infection of female macaques with simian immunodeficiency virus.

The intestinal microbiota modulates host physiology and gene expression via unclear mechanisms. Here, Jabs et al. show that variations in the gut microbiota correlate with N6-methyladenosine modifications of host mRNAs in the cecum and liver of mice.

Controlling RNA and protein condensation is helpful in synthetic biology. Here the authors show programmable assembly of synthetic RNA nanostructures into designer membrane-less organelles that selectively recruit ligands via protein-binding aptamers.

Non-small cell lung cancer (NSCLC) is often associated with metastasis to the lungs. Here, the authors perform independent screens and identify NuRD as a co-repressor of ZEB1, and demonstrate TBC1D2b as a downstream target of ZEB1/NuRD complex regulating NSCLC metastasis.

Irisin is shown to mediate beneficial effects on cognitive function associated with exercise and to improve cognitive function in mouse models of Alzheimer’s disease, probably through its direct action in the brain.

A study establishes a scalable approach to engineer and characterize a many-body-localized discrete time crystal phase on a superconducting quantum processor.

It is hoped that quantum computers may be faster than classical ones at solving optimization problems. Here the authors implement a quantum optimization algorithm over 23 qubits but find more limited performance when an optimization problem structure does not match the underlying hardware.

Nebulized mRNA delivery has broad therapeutic potential but has proven challenging. Here, the authors report on a modified lipid nanoparticle with improved conditions to allow nebulization and demonstrate its application for delivering mRNA to the lungs.

AI-enabled diagnostic applications in healthcare can be powerful, but study design is very important to avoid subtle issues of bias in the dataset and evaluation. Coppock et al. demonstrate how an AI-based classifier for diagnosing SARS-Cov-2 infection from audio recordings can seem to make predictions with high accuracy but shows much lower performance after taking into account confounders, providing insights in study design and replicability in AI-based audio analysis.

The Candida albicans toxin, candidalysin, is embedded in an unusual conserved precursor peptide sequence (Ece1). The precursor is not required to block premature pore-forming toxicity, but rather to prevent candidalysin auto-aggregation.

Phosphorus (P) limitation is pervasive in tropical forests. Here the authors analyse the dependence of photosynthesis on leaf N and P in tropical forests, and show that incorporating leaf P constraints in a terrestrial biosphere model enhances its predictive power.

Squidpy enables comprehensive analysis and visualization of spatial omics data and image with high efficiency.

An analysis of human chromosome 15 — which is altered in Prader-Willi and Angelman syndromes — reveals that it resembles a hall of mirrors, as it contains a number of sequence duplications throughout its length. The evolutionary events that may have led to the high number of duplications was also reconstructed.

The plant circadian clock regulates numerous developmental processes such as seasonal growth and flowering time. Here Ritteret al. identify two transcription factors, FRS7 and FRS12, which interact to form a repressor complex that regulates clock output partially by controlling the expression of GIGANTEA and PIF4.

A phenotypic screen led to the identification of potent inhibitors of mouse BAK-driven apoptosis. The compounds interact with VDAC2 and stabilize its interaction with BAK, blocking apoptosis at an early stage to preserve long-term cell survival.

FRESH, a multi-lab collaboration, reveals how data quality, analysis pipelines, and researcher expertise influence reproducibility in fNIRS neuroimaging, highlighting key factors driving variability in hypothesis outcomes.