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The International Brain Laboratory presents a brain-wide electrophysiological map obtained from pooling data from 12 laboratories that performed the same standardized perceptual decision-making task in mice.

An event-based machine learning model developed to detect fluorescent astrocytic activity and neurotransmitter dynamics enables new and accurate approaches to quantifying physiology in brain slices and in vivo.

In this work, authors utilise a prefractionation natural product extract screening platform, which uncovers coniotins, lipopeptaibiotics with broad antifungal activity and a mechanism of action that targets fungal cell wall β-glucan.

Nature Biotechnology’s annual survey highlights academic startups that are, among other things, designing circular RNA therapeutics, tackling cancer with arenaviruses, creating psychedelics without the trip, editing genes and cells in vivo, harnessing the power of autoantibodies and editing the epigenome.

V1298 Tau b is a 20–30-Myr-old Jovian-sized planet with a haze-free, metal-poor atmosphere and a potentially hot interior. These properties suggest that V1298 Tau b formed in situ via pebble accretion and that it is still evolving and likely to become a Neptune- or sub-Neptune-sized planet.

Propagation of membrane tension mediates communication on the membrane surface. It is now shown that membrane-bound obstacles can obstruct tension propagation, which helps to localize signalling.

This study presents the crystal structure of a BRCA2-DMC1 complex revealing how BRCA2’s PhePP motifs stabilise RAD51 and DMC1 nucleoprotein filaments during DNA double-strand break repair by mitotic and meiotic recombination.

An approach combining bioorthogonal chemistry with genetically encoded fluorogen-activating proteins enables subcellular imaging of phospholipids and glycans, as well as the visualization of lipid transport between organelles and lipid asymmetry across membrane leaflets.

Analysis of medulloblastomas in humans and mice shows that the functional consequences of ZIC1 mutations are exquisitely dependent on the cells of origin that give rise to different subgroups of medulloblastoma.

Quantifying rapid and small cellular forces is a major challenge in mechanobiology. Here, the authors show a >2-fold spatially and >10-fold temporally force sampling improvement combining traction force microscopy with total internal reflection fluorescence super-resolution structured illumination microscopy.

Enhanced polyamine depletion in neuroblastoma models decreases translation of mRNA codons with adenosine in the third position, reprogramming the tumour proteome away from cell cycle progression and towards differentiation.

Therapeutic options for patients with renal medullary carcinoma (RMC) are limited. Here the authors report the results of a phase II clinical trial of anti-PD1 nivolumab plus anti-CTLA4 ipilimumab in RMC, associating the activation of a myeloid mimicry program in tumor cells to the rapid disease progression and hyper-progression observed in treated patients.

Eosinophils exist as a functionally heterogeneous population. Whether the heterogeneity is driven by cell-intrinsic or extrinsic factors is underexplored. Here, by leveraging single-cell transcriptomic data and epigenomic analysis, the authors propose that local environmental cues define the gene expression program of murine esophageal eosinophils and identify AP-1 family members, including ATF3, as key regulators of gene expression.

How Meckel-Gruber syndrome protein TMEM67 functions in ciliogenesis and Wnt signaling simultaneously is unknown. Here the authors show that TMEM67 is proteolytically cleaved by the matrix metalloproteinase ADAMTS9 generating two functional isoforms.

An extensive analysis of the JWST-NIRSpec spectrum of GN-z11 shows a supermassive black hole of a few million solar masses in a galaxy 440 million years after the Big Bang.

A super-resolution microscope images live cells in 3D with high speed, large fields of view and minimal photodamage.

New Zealand implemented stringent COVID-19 control measures early after identification of its first case. Here, the authors perform whole genome sequencing of samples taken until 22 May 2020 and find high viral diversity indicative of multiple separate introductions and limited community transmission.

MYCN amplification is common in neuroblastomas. Here the authors analyse the MYCN amplicon structure and its epigenetic regulation by integrating short- and longread genomic and epigenomic data and find two classes of MYCN amplicons in neuroblastomas, one driven by local enhancers and the other by hijacking of distal regulatory elements.

Brown adipose tissue activation of thermogenesis is accompanied by a sequence of events commonly associated with apoptosis, however they evade cell death. Assali et al. show that NCLX prevents mitochondrial calcium overload and apoptosis. Deletion of NCLX, converts a thermogenic signal into a death pathway.

This study identifies long-lived closed and pre-open states of GORK K+ channel through structural and functional analysis, suggesting semi-independent conformational transitions underlying channel activity and promising sites for stomata engineering.

Liu et al. show that SPIN90 dimerizes and binds two Arp2/3 complexes to nucleate two bidirectional actin filaments and the dimerization domain is conserved in multicellular animals, suggesting that the mechanism of bidirectional actin filament nucleation is conserved.

Autophagy is initiated by the Unc-51-like kinase protein kinase complex (ULK1C) and class III phosphatidylinositol 3-OH kinase complex I (PI3KC3-C1). Here, the authors reveal the structure of the 2:1:1 core of ULK1C and its complex with PI3KC3-C1. ULK1C transitions to a 2:2:2 complex in the presence of PI3KC3-C1, suggesting a mechanism for autophagy induction.

Analysis of ATAC-seq and RNA-seq data from stimulated T cells identifies genetic variants that disrupt transcription factor binding sites within ATAC-seq peaks. ATAC quantitative trait loci (ATAC-QTLs) are enriched for autoimmune disease-associated variants.

A machine learning approach is used to analyse multi-omics (proteomics, metabolomics and transcriptomics) data, producing genetic scores for more than 17,000 biomolecular traits in human blood, and identifying possible associations with disease.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

HMGN1 and HMGN2 are ubiquitous nucleosome binding proteins. Here the authors provide evidence that HMGN proteins preferentially localize to chromatin regulatory sites to modulate the plasticity of the epigenetic landscape, proposing that HGMNs stabilize, rather than determine, cell identity.

Fonio millet is a fast growing orphan cereal crop with a great potential for dryland agriculture. Here, the authors report chromosome-scale reference genome assembly and population genomic resources to shed light on genetic diversity, population structure and domestication of fonio millet.

Automated pathotyping of synovial tissue in arthritis is a major unmet need. Here, the authors develop and demonstrate the efficacy of an automated tissue and cellular pathotyping tool for inflammatory arthritis.

A genomic constraint map for the human genome constructed using data from 76,156 human genomes from the Genome Aggregation Database shows that non-coding constrained regions are enriched for regulatory elements and variants associated with complex diseases and traits.

Gene regulatory network architecture and complex dosage effects from paralogue diversification converge to shape phenotypic space, producing the potential for both strongly buffered phenotypes and sudden bursts of phenotypic change.

A deep learning model, WaveCastNet, predicts seismic ground motion in real time. It outperforms traditional methods by accurately forecasting wave behavior, even in rare and large earthquakes, without relying on magnitude or epicenter location data

Sustained drug delivery is critical for patient adherence to chronic disease treatments. Here the authors apply machine learning to engineer multifunctional peptides with high melanin binding, high cell-penetration, and low cytotoxicity, enhancing the duration and efficacy of peptide-drug conjugates for sustained ocular delivery.

Hypertrophic cardiomyopathy-causing mutations in cardiac myosin disrupt its auto-inhibited OFF state, leading to hypercontractility. Here, the authors show that disease-linked mutations remote from intramolecular OFF state interfaces can allosterically impair myosin autoinhibition

Tornadoes, which cause loss of life and damage to property worldwide, may occur in outbreaks of six or more in rapid succession. Here, the authors show that the annual mean number of tornadoes per US outbreak rose over the last 60 years, with the variance increasing four times faster than the mean.

Whilst superlattices containing thin films of 5d transition metal oxides are expected to yield strong interfacial coupling, only weak effects have been observed. Here, the authors report strong coupling between 3d SrMnO₃ and 5d SrIrO₃due to the interplay of strong Coulomb and spin orbit interactions.

Synchronization may occur when naturally oscillating systems are driven by an external modulation, for example, in charge density waves. Here, Juniper et al. visualize the locked modes of synchronization at a microscopic level using a colloidal system.

Observations of optical flares from AT2022tsd (the ‘Tasmanian Devil’) show that they have durations on the timescale of minutes, occur over a period of months, are highly energetic, are probably nonthermal and have supernova luminosities.

The three-dimensional architecture of genome-reduced bacteria is poorly understood. Here the authors combine Hi-C with super-resolution microscopy inMycoplasma pneumoniaeand provide evidence of how supercoiling and local organization influences gene regulation.

Focusing on two ill-characterized subtypes of medulloblastoma (group 3 and group 4), this study identifies prevalent genomic structural variants that are restricted to these two subtypes and independently bring together coding regions of GFI1 family proto-oncogenes with active enhancer elements, leading to their mutually exclusive oncogenic activation.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

A map of cohesin-mediated chromatin loops in 24 types of human cells identifies loops that show cell-type-specific variation, indicating that chromatin loops may help to specify cell-specific gene expression programs and functions.

Single-molecule localization microscopy relies on stochastic blinking events, treated as independent events without assignment to a particular emitter. Here, BaGoL takes low precision localizations generated from multiple emitter blinkings during DNAPAINT and dSTORM and finds the underlying emitter positions with high precision.

The design of photoactivatable fluorophores—which are required for some super-resolution fluorescence microscopy methods—usually relies on light-sensitive protecting groups imparting lipophilicity and generating reactive by-products. Now, it has been shown that by exploiting a unique intramolecular photocyclization, bright and highly photostable fluorophores can be rapidly generated in situ from appropriately substituted 1-alkenyl-3,6-diaminoxanthone precursors.

When a wound heals, different types of branched and bundled actin structure form, each designed to perform a specific function. Experiments and theory now suggest that the actin architecture depends on the stiffness of the cell’s surroundings.

Ultra-deep mapping of genome organization uncovers precise nuclear compartments and diffuse CTCF loops. This work demonstrates that compartment domains segregate the 5′ and 3′ ends of genes and that CTCF loops create proximal structures.

Vaccinia virus recruits host proteins to promote viral release from infected cells. This is achieved by the viral protein A36, which contains three NPF motifs that interact with the host proteins intersectin-1 and Eps15.

Changes in chromatin structure impact gene expression programs by modulating accessibility to the transcription machinery. Here, West et al. explore differences in nucleosome occupancy between mammalian pluripotent and somatic cells and uncover regulatory regions likely to play key roles in determining cell identity.