Search

Synaptic extracellular proteins increasingly emerge as key organizers of neurotransmitter receptors. Here, authors show that an IgLON family cell adhesion molecule directly traps a nicotinic receptor through extracellular interactions.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Modulating the unfolded protein response (UPR) can induce protective dedifferentiation of β-cells in non-obese diabetic mice. Here, the authors show that β-cell deletion of UPR transcription factor XBP1 is protective against diabetes in these mice and characterize the relevant regulatory networks.

Transcriptomic screening identifies pairs of cell-surface proteins that mediate repulsive interactions between axons and dendrites of non-cognate partner neurons, thereby contributing to correct synaptic partner matching.

Pathogenic variants in UNC13A underlie a novel neurodevelopmental syndrome, with three subtypes defined by distinct genotypes with varying clinical and functional impacts characterized in cellular and animal models.

Transition metal trichalcogenides are layered materials with strong in-plane anisotropy, and their vibrational characteristics remain largely unexplored. Here, the authors present high-pressure Raman studies to uncover unusual vibrational effects within this specific class of materials.

Structural lubricity—referring to ultralow levels of friction between atomically flat, incommensurate surfaces—has previously been observed under ultrahigh vacuum. Here, the authors report structural lubricity at gold-graphite interfaces under ambient conditions and on mesoscopic scales.

Nanorobots will likely play a major role in future therapeutic approaches. Here, the authors develop a molecular automaton based on Zinc-BODIPY complexes that can autonomously switch between singlet oxygen generation and fluorescence emission, i.e., therapeutic and diagnostic modes.

Carmona-Rosas, Li and Smith et al. show that two cell surface receptors, latrophilin and Toll-like receptor, interact in Caenorhabditis elegans and mediate strong roles in early development and morphogenesis.

IFNλ4 has posed a conundrum in human immunology, leading to structural and functional questions about the protein. Here, the authors use protein engineering and cryoEM to determine the cytokine-receptor complex structure and lend explanations to its different activity from other type III interferons.

Machine-learning-augmented single-nucleus transcriptomic analysis compared molecular landscapes of immature neurons in the mammalian hippocampus across species, highlighting human-specific gene expression but convergent biological processes.

The neurochemical basis of compulsive behaviour is not well understood. Here, the authors show that levels of glutamate and GABA in the supplementary motor area and anterior cingulate cortex relate to compulsive behaviour in healthy controls and individuals with OCD.

The authors show PTEN mutations, which can cause both congenital hydrocephalus and autism spectrum disorder, disrupt CSF homeostasis and brain connectivity in mice. Reducing mTORC1 activation ameliorates ventricular enlargement and neuronal deficits.

The demethylase KDM5C, mutations in which often lead to intellectual disability, is identified as a crucial player in regulating the precise timing of neurodevelopment together with the WNT signalling pathway.

The mixing of metals to form alloys with enhanced properties has been known at least since the Bronze Age, although being able to predict their properties remains difficult. An analytical model using computational input is now able to quantitatively predict the mechanical properties of metal yield stress in solute-strengthened alloys.

Robo3 is a divergent, multifunctional member of the Robo receptor family that mediates axon guidance by its ligand NELL2 instead of the canonical Slit ligands. Here, the authors present the crystal structures of human Robo3 in complex with NELL1 and NELL2, and they show through biophysical and functional assays how NELL-Robo3 affinity and ligand-induced receptor multimerization control axon guidance activity.

Biological systems are able to self-assemble in non-equilibrium conditions thanks to a continuous injection of energy. Here the authors present a tool to achieve non-equilibrium self-assembly of synthetic and biological constituents with sizes spanning three orders of magnitude.

Genome-wide association meta-analyses identify 26 risk loci for epilepsy, including 19 loci specific to genetic generalized epilepsy. Prioritized candidate genes implicate synaptic processes and overlap with targets of antiseizure medications.

Treatment of patients with relapsed or refractory multiple myeloma with a combination of the BCMA-targeting antibody–drug conjugate belatamab mafodotin with dexamethasone and pomlidomide is safe and shows promising preliminary clinical efficacy.

Pancreatic β-cells are naturally prone to ER stress due to their role in insulin production and secretion. Here, the authors show that chronic ER stress adaptive exhaustion results in an irreversible loss of β-cell function leading to T1D pathogenesis

CHAPLE disease is a lethal syndrome caused by genetic loss of the complement regulatory protein CD55. Lenardo, Ozen and their colleagues report that blockade of C5 complement activation in a small cohort of pediatric patients with CHAPLE disease reduced gastrointestinal pathology and restored their immunity and growth.

A study leveraging transsynaptic tracing demonstrates rapid and extensive integration of human glioblastoma organoids into the mouse brain.

In this largest whole-exome sequencing study of epilepsies to date, the Epi25 Collaborative identified extremely rare variants that confer risk for diverse epilepsy subtypes, highlighting roles in synaptic transmission and neuronal excitability.

Hormonal FABP4 is discovered to be a pivotal regulator of an adipose–beta-cell endocrine axis that coordinates energy status and metabolic organ function, and targeting this axis improved metabolic outcomes.

Controlling the polarization state in ferroeletric materials is a prerequisite for their application. Here an approach is presented to optically manipulate the polarization of ferroelectric BaTiO₃ by exploiting photogenerated carriers at the interface with a two-dimensional semiconducting MoS₂ film.

Duy and Weise et al. combined human functional integrative genomics with mouse experimental biology to reveal a neuroprogenitor-based genetic subtype of human hydrocephalus with defective neurogenesis and altered brain–fluid biomechanics.

Endocytosis and degradation of plasma membrane proteins in the axon initial segment, together with the diffusion-barrier mechanism, maintain a polarized distribution of plasma membrane proteins in Caenorhabditis elegans, mouse, rat and human neurons.

A supramolecule that inhibits the colony stimulating factor 1 and SIRPα receptors on macrophages significantly enhances antitumour and antimetastatic efficacies in two aggressive animal models of melanoma and breast cancer.

Genomic analyses in individuals with index and familial intracranial aneurysms and experiments in vertebrate models identify pathogenic variants in the PPIL4 gene implicated in cerebral angiogenesis and cerebrovascular integrity, through the Wnt signaling pathway.

Inflammasome inhibitors have potential in psoriasis treatment. Here, the authors report on a study into the shape effects of non-spherical anti-inflammatory lipid nanoparticles made from inflammasome inhibiting lipid and demonstrate application in reducing inflammasome formation in psoriasis in vivo models.