Results 181 to 190 of about 3,163,162 (241)

A Unifying Thermodynamic Model for Phase Separation and Aging of Biopolymers

open access: yesAdvanced Science, EarlyView.
Phase separation and aging of intrinsically disordered proteins are placed in a unifying framework. A thermodynamically consistent time‐dependent version of associating‐polymer theory shows how the processes are intricately coupled. Assuming aging to occur through interacting sites resulting from reversible conformational transitions, the model ...
Jasper J. Michels   +2 more
wiley   +1 more source

Cancer‐Associated BCL‐2 Mutants Reveal Mechanisms Towards Venetoclax Resistance

open access: yesAdvanced Science, EarlyView.
Venetoclax (VEN) resistance in chronic lymphocytic leukemia arises from diverse BCL2 mutations. We map mechanisms contributing to VEN resistance across common BCL‐2 variants. G101V and D103Y reduce drug binding and increase sequestration of pro‐apoptotic proteins. V156D blocks VEN allosterically.
Jonas Aufdermauer   +9 more
wiley   +1 more source

Integrated Single‐Cell and TCR Profiling Reveals Protection‐Associated CD8+ T Cell Subsets Linked to Viral Control in PRRSV

open access: yesAdvanced Science, EarlyView.
PRRSV vaccine‐mediated protection is associated with clonally expanded cytotoxic CD8+ T cell subsets driven by viral structural proteins and supported by innate TLR4/TLR8 signaling and CD4+ T cell help, whereas non‐protective responses are characterized by dysfunctional exhausted‐like CD8+ T cells linked to poor viral control.
Can Kong   +14 more
wiley   +1 more source

Trafficking Deficiency of TMEM175 Variants in Parkinson's Disease Pathogenesis and the Prospects of Precision Medicine

open access: yesAdvanced Science, EarlyView.
This study identifies that the PD‐associated TMEM175‐L156P variant disrupts lysosomal ion channel trafficking by causing aberrant endoplasmic reticulum retention. A “chaperone–agonist” bifunctional small molecule restores TMEM175‐L156P lysosomal localization and channel function, thereby alleviating PD‐relevant cellular phenotypes and highlighting a ...
Ting Luo   +17 more
wiley   +1 more source

Aberrant GRP78 Phase Transition Sustains Endothelial IRE1α Signaling and Drives Blood–Brain Barrier Failure in Cerebral Amyloid Angiopathy

open access: yesAdvanced Science, EarlyView.
Vascular Aβ40 corrupts GRP78 phase behavior in brain endothelial cells, sustaining IRE1α–TRAF2–JNK signaling and driving apoptosis, tight junction loss, and blood–brain barrier failure in cerebral amyloid angiopathy. Pharmacological IRE1α inhibition restores vascular integrity, reduces leakage, and improves functional outcomes, revealing a targetable ...
Honglin Zheng   +19 more
wiley   +1 more source

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