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Different types of SETBP1 variants cause variable developmental syndromes with only partial clinical and functional overlaps. Here, the authors report that SETBP1 variants outside the degron region impair DNA-binding, transcription, and neuronal differentiation capacity and morphologies.

Asexual-to-sexual switching underpins malaria transmission. Prajapati et al. identify an AP2-G loss-of function mutation and use it as a genetic tool to show that GDV1 is essential for initial ap2-g activation and sexual commitment initiation.

Short pulses of high intensity laser light usually heat the ions in dense plasmas indirectly via collisions with the electrons. Here, the authors identify an extremely rapid alternative heating mechanism based on ion-ion collisions.

Upstream open reading frames (uORFs), located in 5’ untranslated regions, are regulators of downstream protein translation. Here, Whiffin et al. use the genomes of 15,708 individuals in the Genome Aggregation Database (gnomAD) to systematically assess the deleteriousness of variants creating or disrupting uORFs.

Ultrack leverages candidate segmentations from multiple algorithms and temporal consistency across time points for robust, long-term 3D segmentation in challenging samples such as densely packed zebrafish, fruit fly and nematode embryos.

Activity recognition in live-cell imaging is laborious. Here, authors present, IVEA, a fully automated AI ImageJ plugin, that efficiently detects and classifies exocytosis events, from synaptic transmission to single-vesicle fusion, across cell types and imaging setups.

Therapies combining chemotherapy and immune checkpoint inhibitors have shown limited efficacy in patients with advanced pancreatic ductal adenocarcinoma (PDAC). Here the authors report the results of a pilot phase 1 trial of neoadjuvant modified Folfirinox plus nivolumab in borderline-resectable PDAC, including safety, efficacy and immunological correlates.

Effective communication of uncertainty is vital for public accurate understanding of climate science. Here the authors find that projections using positive probability terms (for example, a small probability) are perceived as more scientific and trustworthy than those using negative terms (for example, unlikely).

Laboratory astrophysics experiments can provide useful insight into processes such as cosmic ray acceleration, yet the understanding of these phenomena is still incomplete. Here, the authors provide an experimental study of ion acceleration and diffusion at the GSI facilities, providing insight into wave-particle interactions and lower-hybrid drift instabilities.

BRCA1 and BRCA2 are well known breast cancer predisposition genes, however, many variants have not yet been classified for their pathogenicity. Here, the authors analyse a large combined cohort to provide evidence of variant pathogenicity.

An unusual ultraviolet compact object associated with a dusty starburst has been observed at a redshift of about 7.2, with a luminosity that falls between that of quasars and galaxies, possibly in transition between the two. 

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

The ZFTA–RELA fusion, an oncogene for ependymomas, promotes the production of itaconate, and its dependence on this metabolite represents a new therapeutic target for this cancer.

Negative regulation of the cGAS-STING pathway is crucial to limit damaging inflammation. Here, by combining in vitro experiments and myeloid cell-specific conditional knockout mice, the authors identify the autophagy receptor TAX1BP1 as a negative regulator of STING by targeting it for degradation through Golgiphagy and ESCRT-mediated microautophagy.

Reliable measuring the voltage dynamics of individual neurons in the intact brain is significantly challenging. Here authors developed an all-optical method combining two-photon voltage imaging and optogenetics to measure and induce synaptic plasticity in vivo, revealing LTP of inhibition in cerebellar circuits and providing a blueprint to link synaptic changes to learning.

This study uncovers hidden atomic order in high-entropy ceramics and shows it can be engineered to dramatically boost resistance to radiation damage, opening a new pathway for design of ceramics for extreme environments.

In topological insulators, studies have largely concentrated on the spin part of the wavefunction. But the spin–orbit coupling is strong, so the orbital components of the wavefunction need to be measured as well. Surprisingly, the orbital wavefunction turns out to be asymmetric about the Dirac point.

A secondary zone of subsidence near the volcanic arc in subduction zones is indicative of the locking state of the megathrust, which for the Lesser Antilles megathrust suggests that it is locked, according to numerical simulations and deformation data.

Current human tandem repeat catalogs are derived from short-read sequencing data, thus limiting the size range and sequence complexity of captured genotypes. Here the authors generate a comprehensive catalog de novo using long-read sequencing data.

Genome-wide association meta-analysis identifies 58 independent risk loci for major anxiety disorders among individuals of European ancestry and implicates GABAergic signaling as a potential mechanism underlying genetic risk for these disorders.

Ju et al. show that during three-dimensional cell migration, compression recruits cytoplasmic linker-associated proteins to microtubules; these stabilized microtubules then coordinate nuclear positioning and contractility in confined migration.

Hirosawa et al. use single particle tracking and superresolution imaging to demonstrate that tumor-derived small extracellular vesicles (sEVs) undergo clathrin-independent endocytosis, with some using caveolae, facilitated by paracrine sEV binding-induced signaling in recipient cells.

Non-invasive strategies to detect and track activated myeloid cells will facilitate disease diagnosis and monitoring in patients affected by neuroinflammatory disorders. Here, the authors present 18F-FMD, a dendrimer-based PET tracer that detects and monitors activated myeloid cells at different stages (presymptomatic and symptomatic) of Experimental Autoimmune Encephalomyelitis (EAE) in mice and in response to disease-modifying therapies.

Patients with meningioma, the most common type of intracranial primary tumour, have been traditionally managed with surgery and radiotherapy, although advances over the past decade have brought about promising novel treatment options. In addition, new molecularly driven classification tools can improve prognostic accuracy and guide personalized management decisions. The authors of this Review provide an integrated roadmap for meningioma care as well as a framework for ongoing and future research in this field.

Extending their previous findings of brain changes in a first pregnancy, the authors show that a second pregnancy uniquely alters women’s brains, involving both a further fine-tuning of first-pregnancy effects and distinct changes in other networks.

Electron tomography enables high-resolution 3D imaging but is limited by radiation sensitivity. Here, the authors demonstrate a phase retrieval method using multiple tilted HRTEM focal series, achieving 1.6 Å resolution with improved dose efficiency and elemental sensitivity.

Genomic deletions in poxviruses are not well understood, the authors found large deletions in >2% of Mpox virus genomes during routine surveillance, highlighting their role in poxvirus evolution and potential impact on diagnostics and therapeutics.

How cerebellum controls motor timing for error-driven motor learning remains elusive. Here, authors show that the cerebellum sends error-related signals to the premotor cortex to adjust motor timing during learning, and later provides precise timing signals, highlighting its role in controlling when to move in goal-directed behavior.

The authors uncover a direct, BAI1-dependent, role for C1q in the control of neural stem cell proliferation and quiescence via MDM2–p53 and p32, a complement cascade-independent mechanism of C1q action that has implications for central nervous system health and disease.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer due to late detection and rapid progression. Here, the authors integrate multi-regional whole genome and RNA sequencing to characterize intratumoural heterogeneity and evolutionary trajectories underlying the malignant transformation of intraductal papillary mucinous neoplasms into invasive PDAC.

MK-7762 is a new oxazolidinone antitubercular agent that is structurally similar to linezolid, and demonstrated in vivo efficacy, lesion penetration and limited toxicity compared to linezolid, indicating it could be used in broad tuberculosis regimens.

Observations of a fast X-ray transient reveal that it is a gamma-ray-burst explosion from a very distant galaxy that emits light with the wavelength necessary to drive cosmic reionization, the last major phase change in the history of the Universe.

The transmission spectrum of the exoplanet WASP-39b is obtained using observations from the Single-Object Slitless Spectroscopy mode of the Near Infrared Imager and Slitless Spectrograph instrument aboard the JWST.

Active galactic nuclei are surrounded by a dusty and molecular disk that fuels supermassive black holes and connects them to their host galaxies. Here, the authors show with JWST interferometric observations that most of the dust in the Circinus galaxies lies in a compact disk, while only a tiny fraction traces hot outflowing material.

Populations of cerebellar neurons encode both the size and direction of motor errors, enabling the brain to rapidly adjust movements from one trial to the next.

Cadherin-based junctions connect cells to support tissue architecture. Here, the authors show that the condensation of core component β-catenin organizes cadherin complexes into clusters to promote formation of new adhesions.

Pathology-oriented multiplexing (PathoPlex) represents a framework for widespread access to multiplexed imaging and computational image analysis of clinical specimens at a relatively high throughput and subcellular resolution.

CRISPR-Cas9 technology holds the potential to treat a wide spectrum of genetic diseases. Here, the authors describe a modular platform for extracellular vesicle-based Cas9 delivery, using MS2-based RNA-binding domains and UV-cleavable linkers, suitable for various Cas9-based moieties.

The conserved eukaryotic heterotrimeric NatC complex co-translationally acetylates the N-termini of numerous target proteins. Here, the authors provide insights into the catalytic mechanism of NatC by determining the crystal structures of Saccharomyces cerevisiae NatC in the absence and presence of cofactors and peptide substrates and reveal the molecular basis of substrate binding by further biochemical analyses.

Discovery proteomics offers deep insights but is currently not applied clinically in diagnostics. Here, the authors present ADAPT-MS, a flexible machine learning framework that enables fast, personalized diagnostic and prognostic decisions directly from proteome-wide data.

Engineered mucus-tethering bispecific nanobodies neutralize and entrap viruses to enhance mucosal immunity, preventing influenza infection and limiting SARS-CoV-2 transmission.