Search

Michael Bruford and colleagues report whole-genome sequencing of the peregrine (Falco peregrinus) and saker falcon (Falco cherrug). Their comparative analysis with five avian species provides insight into falcon evolution and adaptation to a predatory lifestyle.

The open-source FALCON and FALCON-Unzip software utilize long-read sequencing data to generate contiguous, accurate and phased diploid assemblies, even from genomes that are highly heterozygous.

Membrane budding plays pivotal roles in cellular processes, but a fully artificial system mimicking natural budding processes remains elusive. Here, the authors report a DNA origami-based membrane budding system that recapitulates key aspects of clathrin-mediated endocytosis without relying on components of cellular budding machineries.

Defective neurotransmission is a hallmark of spinal muscular atrophy (SMA). Here, the authors show that local presynaptic Munc13-1synthesis is defective in SMA and that modification of the Munc13-1 mRNA rescues presynaptic architecture and excitability.

Over 20 species of geographically and phylogenetically diverse bird species produce convergent whining vocalizations towards their respective brood parasites. Model presentation and playback experiments across multiple continents suggest that these learned calls provoke an innate response even among allopatric species.

Neuroinflammation following intracortical microelectrode implantation impairs long-term brain-machine interface performance. Here, the authors developed a nanoparticle-based therapy that improves local hemostasis and delivers dexamethasone, reducing inflammation.

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.

Proteomic data from natural isolates of Saccharomyces cerevisiae provide insight into how these cells tolerate aneuploidy (an imbalance in the number of chromosomes), and reveal differences between lab-engineered aneuploids and diverse natural yeasts.

Dendritic cells are supplied antigens by other cells such as lymphatic endothelial cells (LEC) at late time points after immunization. Here the authors show antigen archiving is defined by a transcriptional program that can predict antigen archiving depending on the priming pathogen, and that boosting of immune responses increases the archiving.

Tilt-corrected bright-field scanning transmission electron microscopy offers enhanced cryogenic electron microscopy contrast and substantial improvement in dose efficiency for thick samples such as bacterial cells and large organelles, while still being able to perform single-particle analysis.

Bodogai et al. identify a unique subset of CD8⁺ T cells expressing CD39 and CD73 that accumulate during aging and are recruited to and actively promote tumor progression by suppressing antitumor CD4⁺ T cells. Targeting their function or recruitment attenuates tumor growth in aged mice.

The Vertebrate Genome Project has used an optimized pipeline to generate high-quality genome assemblies for sixteen species (representing all major vertebrate classes), which have led to new biological insights.

EXO1 performs multiple roles in DNA replication and DNA damage repair (DDR), but its role in DDR-deficient cancers remains unclear. Here, the authors find EXO1 loss as synthetic lethal with many DDR genes involved in various cancers, including genes from Fanconi Anaemia pathway, BRCA1-A complex, and spliceosome factor ZRSR2; such interactions represent potential clinical targets.

Distinct subsets of conventional DCs (cDCs) promote the differentiation of distinct helper T cell lineages. Here, the authors identify a GM-CSF-dependent cDC2 population in the mouse lung that expresses CD301b at steady state and promotes the differentiation of Treg cells, whereas during the initiation of allergic responses, these cDC2s transition to CD200⁺ cDC2s, promoting Th2 differentiation.

High-fidelity reads improve variant detection and genome assembly on the PacBio platform.

Malaria control and elimination require environmentally safe strategies. Here, the authors propose L-DOPA, a naturally occurring tyrosine derivative, as a mosquito dietary intervention that can shorten lifespan and reduce malaria parasite burden of female Anopheles gambiae mosquitoes.

Aging leads to progressive loss of effective tissue regeneration, which has been linked to the accumulation of senescent cells. Here, the authors use machine learning to identify a stable nuclear morphometric phenotype that detects senescent cells across tissues and age, enabling their quantification and mapping in diverse environments.

Which combination of current genome sequencing and assembly approaches results in high-quality, complete diploid genome assemblies is determined.

A pangenome of the Cannabis genus including 193 genomes demonstrates high variability in most of the genome but low diversity in cannabinoid synthesis genes and provides a resource for future genetic studies and crop optimization.

Chapman, Klaourakis and colleagues reveal that a lymphatic vasculature with poor clearance capacity in perinatal, regeneration-competent mouse hearts is required to retain pro-reparative macrophages and allow cardiac regeneration.

Disulfide-based dimerization of modified identical and heterologous nanobody scaffolds enables higher-order assembly for high-resolution cryo-electron microscopy structure determination that is widely applicable to small protein targets.

The MRN complex plays a key role in detecting, signalling, and processing DNA double-strand breaks. This study reports the cryo-EM structures of human MRN bound to DNA, alone and with telomeric protection factor TRF2, revealing MRN’s structural transitions and regulatory mechanisms.

An improved, fully re-annotated Aedes aegypti genome assembly (AaegL5) provides insights into the sex-determining M locus, chemosensory systems that help mosquitoes to hunt humans and loci involved in insecticide resistance and will help to generate intervention strategies to fight this deadly disease vector.

The transcription factor ATF6 causes an enrichment in long-chain fatty acids in the colonic epithelium, which leads to changes in the gut microbiota and contributes to the development of colorectal cancer in humans and mice, thereby linking endoplasmic reticulum stress responses to lipid metabolism and tumorigenesis.

Zorya uses a membrane-anchored H⁺-driven rotary motor ZorAB to sense phage invasion and to recruit the intracellular effectors ZorC and ZorD that execute anti-phage defence.

High-resolution data are crucial for accurate structural modeling. Here, authors enhance MicroED data quality using energy filtering, achieving sub-atomic resolution protein data and uncovering diffuse scattering, offering detailed insights into protein structure and function.

TRPML2, a lysosomal TRP channel, regulates endolysosomal integrity and chemokine secretion. This work reports the cryo-EM structures of TRPML2 in multiple states bound to modulators revealing its diverse regulatory mechanisms among ion channels.

Human iPSC-CMs are invaluable for cardiac disease modeling and regeneration. Here, authors developed an optimized suspension culture protocol to efficiently and reproducibly differentiate hiPSCs into cardiomyocytes and cardiac organoids.

A highly potent and selective small-molecule catalytic inhibitor of the protein lysine methyltransferase NSD2 shows therapeutic efficacy in preclinical models of KRAS-driven pancreatic cancer and lung cancer.

This article reports sub- and near-atomic structures of triclinic lysozyme and serine protease proteinase K, respectively, providing first demonstrations of ab initio phasing using electron counted MicroED data to solve macromolecular structures.

Inflammatory monocytes in the brain meninges promote stress-induced fear behaviour, and the pathways involved can be modulated using psychedelic compounds.

The enzyme ABHD18 is shown to have a key role in cardiolipin metabolism in mitochondria, offering a potential route for a small-molecule treatment of the rare genetic disease Barth syndrome.

A deep chemical proteomic investigation of diverse aminophilic electrophiles has identified ligandable lysines across a wide range of human proteins. The proteins cover different functional and structural classes, and the aminophilic electrophiles include compounds that disrupt protein–protein and protein–RNA interactions. This dataset provides a proteome-wide atlas of lysine-reactive chemistry.

The development of subunit vaccines mimicking the molecular complexity of attenuated vaccines has been limited by the difficulty in co-delivery of multiple chemically diverse payloads. Here, the authors report hierarchical hydrogels, assembled from a single homopolymer via a multi-stage process, that enable ratiometric loading of a protein antigen and four physicochemically distinct adjuvants.

North Africans are underrepresented in current genome-wide data sets. Here, the authors provide an Egyptian genome reference, consisting of de novo assembly of the genome of an Egyptian individual and genome-wide genetic variation from a representative cohort of 110 Egyptian individuals.

Certain antimetabolites used to treat cancer are more neurotoxic than others, and it is now shown that this is due to their greater tendency to generate DNA double-stranded breaks, whereas less neurotoxic agents induce single-stranded breaks.

The BRCC36 isopeptidase complex (BRISC) is a deubiquitylase that stabilizes interferon receptors, driving inflammation. We discovered ‘BRISC molecular glue’ inhibitors (BLUEs) that selectively inactivate BRISC, promoting interferon receptor ubiquitylation and degradation to dampen immune responses.

Hippocampal neurons adapt to experience through changes in gene expression and chromatin accessibility. Here, authors show that novel environment exposure induces region- and cell-type specific transcriptional changes coordinated by FOS/AP-1.

Genetic disposition can impact response to virus infection. Here, the authors used a reinfection approach with antigenically distinct SARS-CoV-2 variants Omicron and Beta and show that differences in the immune response correlate with disease outcome in mouse models with different genetic background upon reinfection.

Lymphostatin is a large protein required for Escherichia coli virulence. Here, Griessmann et al. use electron cryo-microscopy to describe the structure of lymphostatin determined at different pH values, showing three conformations, six distinct domains, and long inter-domain linkers that occlude the catalytic sites of the N-terminal glycosyltransferase and protease domains.

A population of TRAIL-positive astrocytes in glioblastoma contributes to an immunosuppressive tumour microenvironment and this mechanism can be targeted with an engineered oncolytic virus to improve outcomes.

Single-cell transcriptomic analysis of mouse hypothalamus and behavioural experiments show that specific hypothalamic networks regulate conflicting feeding versus parenting behaviours of female mice.

In a prospective, regulatory-grade study of assistance to pathologists in MASH histology scoring, AIM-MASH-assisted reads by expert MASH pathologists were superior to unassisted reads and decreased inter-reader variability.

Dynamic interface printing is a new form of 3D printing that leverages an acoustically modulated, constrained air–liquid boundary to rapidly generate centimetre-scale 3D structures within tens of seconds.

Bacterial Type I polyketide synthases are responsible for producing both lifesaving medicines and virulence factors, yet their stepwise mechanism remains elusive. Here, Burkart et al. characterize acyl carrier protein bound states of mycocerosic acid synthase from Mycobacterium tuberculosis through crosslinking and cryo-EM.

The notothenioid radiation is a remarkable group of fish adapted to life in the icy waters of the Southern Ocean. This study investigates the evolutionary history of this group and the basis of their adaption to cold environments through genomic analysis of 24 new genome assemblies.

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.

Adriaenssens et al. show that unlike soluble cargo receptors, transmembrane cargo receptors initiate autophagosome biogenesis by recruiting the FIP200/ULK1 or WIPI–ATG13 complex, revealing unexpected flexibility in the selective autophagy machinery.