Results 161 to 170 of about 10,613 (255)

Development and Structural Characterization of UTE‐156, a Covalent Inhibitor of the VCP/p97 AAA+ ATPase

open access: yesAdvanced Science, EarlyView.
The AAA+ ATPase Valosin‐containing protein (VCP/p97) regulates protein homeostasis by unfolding ubiquitinated substrates. Here, we describe UTE‐156, a novel irreversible covalent inhibitor that modifies Cys522 in the D2 ATPase motor domain. Although its pharmacochemical limitations preclude immediate therapeutic use, UTE‐156 serves as a valuable ...
Daniela Tamayo‐Jaramillo   +8 more
wiley   +1 more source

T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities

open access: yesAdvanced Science, EarlyView.
T cell exhaustion limits immunotherapy efficacy. This article delineates its progression from stem‐like to terminally exhausted states, governed by persistent antigen, transcription factors, epigenetics, and metabolism. It maps the exhaustion landscape in the TME and proposes integrated reversal strategies, providing a translational roadmap to overcome
Yang Yu   +7 more
wiley   +1 more source

Postsynaptic Complexin Mediates Constitutive Exocytosis of Nicotinic Acetylcholine Receptor

open access: yesAdvanced Science, EarlyView.
Beyond its established presynaptic role, complexin is identified as a postsynaptic regulator of neurotransmitter receptor trafficking. By promoting constitutive and activity‐dependent exocytosis of nicotinic acetylcholine receptors, complexin controls spontaneous synaptic signaling at the C.
Ya Wang   +4 more
wiley   +1 more source

Nanoscale Spatial Organization of ARC High‐ and Low‐Order Assemblies at Excitatory Synapses

open access: yesAdvanced Science, EarlyView.
ARC (Activity‐Regulated Cytoskeleton‐Associated protein) mediates synaptic plasticity by forming nanoscale assemblies in neurons. Using super‐resolution microscopy and time‐resolved anisotropy with targeted tagging, the study reveals low‐order ARC assemblies at synapses colocalizing with AMPARs, semi‐circular structures at endocytic zones, and 60–80 nm
Martina Damenti   +13 more
wiley   +1 more source

Cis‐ and Trans‐Regulatory Factors Independently Shape Phenotypic Heterogeneity of Retinitis Pigmentosa

open access: yesAdvanced Science, EarlyView.
A zebrafish model carrying an identical human RHO S334X allele reveals two independent genetic layers shaping retinitis pigmentosa (RP) severity: a protective 3‐bp cis‐regulatory insertion that attenuates transgene expression, and a dominant trans‐acting modifier that restores a severe phenotype.
Cong Cui   +9 more
wiley   +1 more source

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