Psilocybin reshapes brain networks through activity-dependent plasticity, including a weakening of recurrent cortical loops that could underlie its therapeutic effects.
The force-sensing ion channel PIEZO2 is an essential regulator of the renin-angiotensin-aldosterone system (RAAS), a pathway that controls blood volume. Loss of PIEZO2 in the kidney cells that produce renin disrupts cellular calcium dynamics and levels of the enzyme in mice, linking mechanotransduction in the kidney to the RAAS.
Kidney podocytes of the blood-urine filter form autoimmunoglobulin-triggered extracellular vesicles (AIT-EVs) for intra- and extracellular waste removal into the urine, a cellular reaction that links basal immune complex clearance to podocyte injury and allows non-invasive diagnosis and monitoring of kidney autoimmune activity.
A fin-like structural loop in GPX4 is critical for anchoring the enzyme to cellular membranes, thereby preventing ferroptosis. A patient-associated R152H mutation destabilizes this loop, leading to ferroptotic neurodegeneration in human cells and mouse models and revealing Alzheimer’s-like molecular signatures. These findings position ferroptosis as a critical driver (and potential therapeutic target) of neurodegenerative disease.
(Cell187, 7637–7654.e1–e29; December 26, 2024)
Single-cell proteomics finds asymmetries between sister blastomeres from the 2-cell stage in human and mouse embryos, defining two states: alpha and beta. Alpha-beta asymmetry can be traced back to the zygote, is triggered by fertilization, and is linked to differential developmental potential, with beta blastomeres having a higher potential.
A complete hierarchical thermo-decoding mechanism in plants connects cell membrane lipid remodeling during heat stress to the downstream signaling cascade in the nucleus. Field trials demonstrate the potential application of this mechanism in customized heat-tolerant crop design in rice.
Umbrella toxin particles produced by Actinobacteria contain five spokes tipped with variable lectin domains. Here, Zhao et al. show that these lectins mediate species-specific binding to a previously unrecognized cell surface carbohydrate polymer and propose that the modular nature of umbrella particles enables bet hedging against unpredictable competitor encounters.
Addition of a pre-TCR domain to chimeric antigen receptors boosts mRNA translation and enables durable tumor control by T cells in both blood and solid cancers.
Cells in tissues need to know when to start growing and when to stop growing to quickly heal wounds but prevent tumorous overgrowth. Membrane potential allows cells to sense physical forces, including those from neighboring cells, and thereby regulates growth.
A natural experiment found that herpes zoster vaccination reduced the occurrence of mild cognitive impairment and deaths due to dementia, indicating that the vaccine may slow the progression of dementia throughout its clinical disease course.
Methanogenic archaea use the one-component system AmzR to sense methylamines and regulate the expression of methylamine-metabolizing genes. Unlike other prokaryotic one-component systems, the DNA-binding motif of AmzR resembles a structural fold typically found in eukaryotic transcription factors. This discovery narrows the gap between prokaryotic and eukaryotic regulatory proteins.
Wang et al. identify a new lytic cell death pathway, mitoxyperilysis, triggered by the synergy of innate immune activation and metabolic stress. This process is regulated by mTORC2 and involves persistent mitochondria-membrane contact, leading to localized oxidative damage and cell lysis, with implications for inflammatory diseases and cancer therapy.
Acute stress causes immediate hair follicle necrosis and hair loss via sympathetic nerves, which in turn activates and expands autoreactive CD8⁺ T cells targeting hair follicles. Thus, a single stress event not only causes immediate tissue damage but also predisposes the tissue to future autoimmune attack.
In vitro-derived insights into features that drive transcription factor binding to DNA, including motif-adjacent sequence, enable prediction of chromatin states and transcription factor occupancy in cells.
During sickness, animals exhibit prolonged social withdrawal, a response that may limit disease spread. Elevated IL-1β levels during inflammation activate IL-1R1-expressing neurons in the dorsal raphe nucleus to drive self-imposed withdrawal, highlighting a neural mechanism through which immune activation reconfigures social behavior.
Developing genetic access to transcriptionally distinct enteric neuronsin vivoenables the examination of morphological heterogeneity across cell types as well as cell-type-specific influences on GI function.
(Cell185, 860–871.e1–e4; March 3, 2022)
Interspecies PSC co-culture induces horizontal RNA transfer that activates innate immunity in “winner” mouse cells, a response that is alleviated byMavsdeletion, thereby enhancing “loser” human PSC survival and chimerism.
(Cell188, 3329–3348.e1–e18; June 12, 2025)
A full-length dimeric form of the anti-apoptotic protein BCL-w can block oligomeric BAX-driven mitochondrial permeabilization and apoptosis, revealing a new layer of cell-death control.
Clinical evidence from AD patients reveals an association between impaired CCKBR-Gq signaling and disease severity, guiding structure-based design of a Gq-biased agonist that rescues memory and pathology in AD animal models.
BRAIN-MAGNET, a convolutional neural network trained on 148,198 functionally tested non-coding regulatory elements, predicts enhancer activity directly from DNA sequence and identifies nucleotides essential for function. This functional genomic atlas and BRAIN-MAGNET prioritize disease-relevant non-coding variants, advancing functional interpretation of the regulatory genome in neurodevelopment and neurological disease.
Reduced levels of the essential metabolite heme are a common feature of acute myeloid leukemia, and consequently, leukemic cells are highly sensitive to inhibition ofde novoheme synthesis. Blockade of heme biosynthesis enzymes triggers cuproptosis, a form of copper-dependent cell death that is molecularly distinct from other cell death pathways.
MiTEs are myeloid-targeted immunocytokine prodrugs that block TREM2+tumor-associated macrophages while activating cytotoxic lymphocytes via TME-specific IL-2 activity, eliciting strong anti-tumor efficacy in preclinical models with minimal systemic toxicity.
Systematic profiling of 707 drugs on their impact on stool-derived microbial communities shows that nutrient competition explains and predicts species shifts under drug treatment and that post-drug recovery is driven by ecological interactions like extinction and strain swapping.
Long-lived plasma cells that secrete virus-specific IgA at the mucosae are a key determinant in preventing viral infection. Generation of this response is dependent on a unique subset of follicular helper T cells with a type 1 signature—the helper T cells are generated through unconventional priming by B cells and promote the migration of virus-specific IgA+plasma cells to mucosal effector sites.
Not all cells that can be infected by a virus become infected with that virus. Single-cell clone tracing reveals intrinsic cell states with variable expression patterns that increase susceptibility to viral infection, and this applies for several distinct viruses.
Ancient RNA profiles from Late Pleistocene woolly mammoths were sequenced from permafrost-preserved mummified tissues, revealing tissue-specific transcriptional functions and gene expression regulatory dynamics. These findings highlight the potential of ancient RNA molecules to provide additional biological information, thus advancing toward integrative paleogenetic research beyond the limits of DNA sequencing alone.
Structural and functional analyses of a brain-enriched serotonin receptor, 5-HT1AR, elucidate the molecular basis of Gi/osubtype selectivity, leading to the design of a GoA-preferential agonist that induces rapid antidepressant effects in mice while avoiding autoreceptor activation.
Grammars inferred using NARDINI+ (GIN) is a resource that uncovers molecular grammars of intrinsically disordered regions (IDRs) across the human proteome, revealing how distinct grammars underlie protein localization, function, and disease associations.
Longitudinal ultrasensitive ctDNA detection improves disease stratification accuracy, demonstrates clinical utility for adjuvant therapy, and reveals insights into characteristic features of relapse in patients with non-small cell lung cancer.
Phase separation stabilizes synthetic gene circuits and boosts production under dynamic growth conditions. By locally concentrating transcription factors at promoters, it protects gene expression from growth-driven dilution and provides a broadly applicable strategy for gene circuit engineering.
This study presents a comprehensive evolutionary history of gibbons by resolving their contentious phylogeny, reclassifying an extinct species with ancient DNA, and identifying a structural variant potentially contributing to their limb elongation.
By sidestepping Cas9 immunogenicity, the StealTHY CRISPR platform enables immune-compatiblein vivogenetic screens, directly translatable to humanized cancer models. Using this immune-stealth strategy allows for the discovery of metastatic drivers and reveals the AMH-AMHR2 axis as a clinically actionable pathway for dampening carcinoma metastasis.
