Results 41 to 50 of about 2,621 (151)

DyProL: Dynamic Ensemble Representation Learning for Protein–Nucleic Acid Binding Site Prediction

open access: yesAdvanced Science, EarlyView.
Protein function is represented as a dynamic conformational ensemble rather than a single static structure. A multi‐conformation geometric attention framework aligns, clusters, and learns representative states to capture residue‐ and ensemble‐level signals. Integrating structural dynamics improves interpretable protein‐NA binding prediction and reveals
Pengpai Li   +3 more
wiley   +1 more source

Similarity‐Enhanced Representation Learning of Non‐Canonical Amino Acids for Therapeutic Peptide Modeling

open access: yesAdvanced Science, EarlyView.
Non‐canonical amino acids (ncAAs) enhance peptide therapeutics but remain difficult to model computationally. SinCAA, a similarity‐enhanced pretraining framework, jointly optimizes contrastive learning guided by a novel conformational similarity metric with masked node reconstruction, capturing both functional relationships and chemical identity of ...
Chencheng Xu   +8 more
wiley   +1 more source

Leveraging Microphysiological Systems to Facilitate Neutrophil‐Based Cancer Immunotherapy

open access: yesAdvanced Science, EarlyView.
Microphysiological systems are emerging as powerful human‐relevant platforms for studying neutrophil biology in cancer. Current applications of spheroids, organoids, and organ‐on‐a‐chip models are reviewed, together with future opportunities in behaviorome profiling, multi‐omics integration, personalized medicine, immune crosstalk, and multi‐organ ...
Shuai Shao   +2 more
wiley   +1 more source

Abstract Representation of Movement Parameters in Basal Ganglia Output

open access: yesAdvanced Science, EarlyView.
The basal ganglia output provides a scalable velocity/position signal across behavioral contexts, supporting the idea that these variables are represented in the brain as abstract entities rather than as fixed changes in joint angles or specific sets of body effectors.
Ana Silvia Báez‐Cordero   +3 more
wiley   +1 more source

Probing the Energy Landscape of α‐Synuclein Amyloid Fibril Formation by Systematic K‐to‐Q Mutagenesis

open access: yesAdvanced Science, EarlyView.
We use lysine‐to‐glutamine mutations to study the effect of electrostatics on the kinetics and thermodynamics of alpha‐synuclein amyloid fibril formation. We find that mutational effects map on their structural context within fibrils and identify residues that modulate the energy landscape of alpha‐synuclein self‐assembly. Our work outlines a scalable,
Antonin Kunka   +10 more
wiley   +1 more source

An Unbiased Geometry‐Resolved Membrane Platform for Proteome‐Scale Discovery of Membrane Curvature Sensors

open access: yesAdvanced Science, EarlyView.
A novel geometry‐resolved membrane platform provides a seamlessly integrated pipeline for studying curvature‐sensing proteins. By linking shotgun proteomics with quantitative imaging, this approach enables both the unbiased discovery and rigorous validation of novel sensors across the entire curvature range—positive, negative, and zero.
Takumi Komikawa   +6 more
wiley   +1 more source

Expanding Genetic Code to Generate Human Brain Organoids with Both Vasculature and Microglia‐Like Cells

open access: yesAdvanced Science, EarlyView.
Using genetic code expansion, we engineered vascularized human cerebral organoids (vhCOs) with microglia‐like cells and blood‐brain barrier features. vhCOs recapitulate neurovascular interactions, regional identities, and neuronal subtypes resembling the fetal brain.
Haishuang Lin   +7 more
wiley   +1 more source

Spatial Transcriptomics Reveals a T Cell‐Mediated Microglial Activation Axis of Immune Checkpoint Inhibition‐Related Adverse Events in the Brain

open access: yesAdvanced Science, EarlyView.
Immune checkpoint inhibition (ICI) reshapes the hippocampal neuroimmune niche. Spatial transcriptomic profiling and human brain histological analyses identify neuroinflammation and altered neuronal and glial programs. Notably, T cell depletion prevents ICI‐driven microglial activation, establishing the T cell–microglia crosstalk axis as a driving ...
Devyani Swami   +7 more
wiley   +1 more source

An Extracellular Pore‑Targeting Peptide Defines a Designable Allosteric Site in TRPV2

open access: yesAdvanced Science, EarlyView.
Structure‐guided peptide engineering yields Depiv2, a highly potent and subtype‐selective TRPV2 inhibitor that binds to the extracellular pore and remodels it into a closed, non‐conductive state. Depiv2 suppresses pathological cardiac hypertrophy, establishing the TRPV2 outer pore as a designable interface for selective peptide modulation.
Aiqin Zhu   +7 more
wiley   +1 more source

PLXDC2 siRNA‐Mediated Intervention Attenuates Microglial Senescence Through cGAS‐STING Signaling

open access: yesAdvanced Science, EarlyView.
PLXDC2 was identified as a microglial target in Parkinson's disease through human and mouse single‐cell analyses. Ferritin‐armed biomimetic nanovesicles delivered PLXDC2 siRNA, deferoxamine, and CeO2 nanoparticles across the blood–brain barrier, reducing cGAS‐STING activation, iron burden, oxidative stress, and senescence in microglia, thereby ...
Heyue Lu   +13 more
wiley   +1 more source

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