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Kainate receptors (KARs) contribute to excitatory neurotransmission, neuronal plasticity and neurological disorders. Here, Gangwar et al. present KAR structures in complex with channel blockers NpTx8, PhTx74, KukoA, and spermine, which become trapped inside the channel upon its closure.

DNA nanotechnology, including DNA machines and devices for computing, is a rapidly expanding field of research. Here, the authors fabricate DNA catenane machines for the programmable arrangement of gold nanoparticle cargoes, and study their switchable spectroscopic features.

Here they show that the adhesion GPCR Gpr126/Adgrg6 regulates trabeculation during heart development. Its N-terminal fragment is required for maintaining cell adhesion and compact wall integrity while its C-terminal fragment is essential to provide trabecular identity.

The astrocytic transporter, GAT3, is a drug target for epilepsy. Here, the authors report the structures of human GAT3, bound to an inhibitor, to substrate GABA, or in substrate-free state, revealing the mechanism of transport and selective inhibition.

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.

Active neurons increase their energy supply by dilating nearby arterioles and capillaries to increase blood flow, but the mechanisms underlying neurovascular coupling are debated. In this paper, the authors show that different calcium-dependent signaling pathways regulate blood flow at the level of capillary pericytes and arteriole smooth muscle.

The loss of nerve cells in the brain is the main event causing life-long deficits and neurological problems after stroke. Weilinger et al. show that NMDA receptors cause nerve cell death during stroke in an unexpected way. Although they require ligand binding and recruitment of downstream pannexin channels, NMDA receptors do not use the receptor's ion channel.

Replicating intercellular communication in synthetic cells is challenging. Here, the authors report on engineered connexin nanopores that can be controlled with light to exchange distinct chemical signals between synthetic cells, creating programmable communication networks that mimic cellular interactions.

The authors report the structure of human oncochannel TRPV6 in complex with the plant derived phytoestrogen genistein. The structure provides insights into genistein binding in the channel pore, and how it acts as blocker and gating modifier, suggesting a mechanism of inhibition that can be explored for the structure-based drug design.

The tolerogenic activity of type 1 conventional dendritic cells (cDC1s) is determined by EPOR, which is preferentially expressed in cDC1s and induces antigen-specific FOXP3-expressing regulatory T cells.

Mapping of the neutrophil compartment using single-cell transcriptional data from multiple physiological and patological states reveals its organizational architecture and how cell state dynamics and trajectories vary during health, inflammation and cancer.

MicroRNAs regulate gene expression through selective pairing with target mRNAs. Here, the authors reveal distinct, mutually exclusive binding modes of miRISC at the 5′ seed and 3′ non-seed regions, advancing understanding of RNA silencing mechanisms.

GluA2-containing AMPA receptors (AMPARs) are not Ca²⁺ impermeable, and their ability to transport Ca²⁺ is shaped by the subunit composition of AMPAR tetramers as well as the orientation of transmembrane AMPAR regulatory proteins and cornichon auxiliary subunits.

Three-dimensional residual channel attention networks (RCAN) enable improved image denoising and resolution enhancement on volumetric time-lapse fluorescence microscopy data, allowing longitudinal super-resolution imaging of living samples.

Studies in humans and mice show that myocardial infarction recruits monocytes to the brain’s thalamus, promoting sleep, which in turn restricts cardiac inflammation and sympathetic signalling and assists healing.

Synaptic plasticity ensures functionality during perturbations and enables memory formation. Here, the authors describe homeostatic functional and nano-modular active zone modifications for immediate and long-lasting enhancement of neurotransmitter release, and identify Unc13 as a presynaptic molecular target for homeostatic potentiation and learning.

Durable agonism of NPR1 achieved with a novel investigational monoclonal antibody could mirror the positive hemodynamic changes in blood pressure and heart failure identified in humans with lifelong exposure to NPR1 coding variants.

Small molecules targeting transient receptor potential (TRP) channels might be used to control pain. Here, Neuberger et al. report cryo-EM structures of human TRPV1 in the absence of added ligands or in the presence of the TRPV1-specific antagonist SB-366791, providing insights for the design of new promising analgesics.

Experiments in mice show that a population of neurons in the vagal ganglia respond to the presence of glucose in the gut and connect to neurons in the brainstem, revealing the circuit that underlies the neural basis for the behavioural preference for sugar.

PU.1^low CD28-expressing microglia may act as suppressive cells in Alzheimer’s disease, mitigating its progression by reducing neuroinflammation and amyloid plaque load, indicating potential immunotherapeutic approaches for treatment.

Genes2Genes is a dynamic programming framework that enables precise alignment for single-cell trajectories at the per-gene level.

Ovarian cancers frequently develop resistance to therapy. Here, using transcriptomics, proteomics, and preclinical models to analyse paired ascitic fluids before and after chemotherapy in ovarian cancer patients, the authors discover that extracellular secretion and spliceosomal components contribute to therapy resistance, enhancing the DNA damage response in recipient cancer cells.

Fluid shear stress plays a role in medulloblastoma metastasis through a PIEZO2-actomyosin-GLUT1 signalling cascade.

Here the authors show that lowering IGF-1R levels in endothelial cells improves insulin sensitivity, boosts energy use, and supports beneficial changes in adipose tissue, offering insights into potential treatments for obesity-related metabolic disorders.

Nitric oxide (NO) and hydrogen sulphide (H₂S) are two gaseous signalling molecules produced in tissues. Here the authors propose that NO and H₂S react with each other to form nitroxyl (HNO), which activates the TRPA1 channel in nerve cells and triggers the release of the vasoactive peptide CGRP.

Two broadly reactive and inhibitory human monoclonal antibodies against the malaria parasite Plasmodium falciparum have been characterized, providing insights into immunity, prevention and treatment of severe malaria.

In this study, the authors use selective silencing of specific subsets of afferent neurons and stimulation with pruritogens or algogens to show that histaminergic and non-histaminergic itch is mediated by functionally distinct sets of sensory fibers. These findings provide further evidence for the labeled line theory of sensory perception.

Intraventricular hemorrhage is one of the most fatal forms of brain injury. It is a common complication in premature infants and has limited treatment options. Here, the authors show that transcranial photostimulation can ameliorate lymphatic removal of blood from the brain of adult and newborn rodents after intraventricular hemorrhage, providing fast recovery and improvement of behavioral outcomes.

Evolutionary conservation of plant receptor structure allowed for generation of new variants of wheat and barley nucleotide-binding leucine-rich repeat receptors (NLRs) that recognize AvrSr35 of the wheat stem rust pathogen, supporting proof of principle for structure-based engineering of NLRs for crop improvement.

TRPV6 is a calcium-selective ion channel that is involved in numerous calcium-dependent physiological processes and it is of interest as a potential drug target. Here, the authors present the cryo-EM structures of human TRPV6 with the bound inhibitors ruthenium red and the antifungal drug econazole and discuss their inhibition mechanisms.

Oxidative stress is associated with cardiovascular and neurodegenerative diseases. Here the authors show studies of transgenic chemogenetic mouse lines that develop sensory ataxia and cardiac hypertrophy caused by neurovascular oxidative stress.

Inorganic polyphosphates have been identified in the central nervous system. Holmström and colleagues examine neuroglial cultures in vitro and cardiorespiratory responses in vivo, and find that inorganic polyphosphates trigger calcium-dependent activation of astrocytes and increase cardiorespiratory activity.

Karpf et al. showed that distinct layers of the adult human and mouse DG are populated by astrocytes, which exhibit a subtype-specific molecular profile and morphology, leading to subtype-specific physiological characteristics.

DNA probes used in next generation sequencing (NGS) have variable hybridisation kinetics, resulting in non-uniform coverage. Here, the authors develop a deep learning model to predict NGS depth using DNA probe sequences and apply to human and non-human sequencing panels.

Drug resistance remains a major challenge in cancer treatment. Here, the authors identify Connexin43 as target that enhances BRAF/MEKi efficacy by interfering with DNA repair pathways, overcoming drug resistance. They develop an mRNA therapy that improves efficacy and sensitizes resistant cells.

The depolarizing funny current contributing to cardiac pacemaking is upregulated in the myocardium of  failing and infarcted hearts, but whether the current is implied in disease mechanisms is unclear. Here the authors generate HCN4 transgenic mice and show that upregulation of funny current to the levels observed in human heart failure alters calcium homeostasis leading to cardiac remodelling and arrhythmia.

Here, Biswas et al. present and characterize a second-generation model of HBV infection in rhesus macaques, showing that extended infection requires suppression of host immunity.

Two doses of the coronavirus disease 2019 vaccine ChAdOx1 nCoV-19 boost antibody responses and functions in phase 1/2 trial participants.

Palmitoylation is a post translational modification that regulates GPCR activity. Here the authors show that palmitoylation of 5-HT1AR by the palmitoyltransferase enzyme ZDHHC21 contributes to depression-like behaviour in rodents and might be implicated in major depressive disorder.

Obstructive lung diseases are a frequent cause of morbidity worldwide. Here, the authors identify the endocannabinoid anandamide (AEA) as an airway relaxant under physiological and pathophysiological conditions that can be locally applied to the lung as an aerosol in mice.

Current approaches to detect allograft damages non-invasively are limited and do not differentiate between cellular mechanisms. Here, the authors show that the composition of cell-free DNA in blood samples can reveal cellular causes of allograft injury after liver transplant.

Il-13 is expressed in neurons and IL-13 ko causes memory impairment. Here, authors show that IL-13 and its receptor IL-13Ra1 are pre- and post-synaptic proteins, respectively, involved in synaptic signaling, plasticity and neuroprotection.

In a prespecified analysis of the FLOW trial, the use of an SGLT2 inhibitor did not impact the overall benefits of semaglutide on kidney and cardiovascular outcomes in participants with type 2 diabetes and chronic kidney disease.

The neurotransmitter noradrenaline can regulate cellular processes that contribute to cancer progression, but the underlying mechanisms remain largely unknown. Here the authors identify Src as a key mediator of noradrenaline signalling networks in tumour metastasis.