Results 221 to 230 of about 1,274,843 (306)

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

A Second Pathogenic Protein, PolyGN2C‐iso2, Reveals a Dual‐Protein Pathology in Neuronal Intranuclear Inclusion Disease

open access: yesAdvanced Science, EarlyView.
This study reveals that NOTCH2NLC transcript variant 2 generates PolyGN2C‐iso2, an aggregating protein present within intranuclear inclusions of NIID patient tissues. A novel mouse model expressing PolyGN2C‐iso2 recapitulates white matter abnormalities and cognitive deficits, mechanistically linked to mitochondrial dysfunction. These findings support a
Kang Zhang   +22 more
wiley   +1 more source

Immediate Growth Control in Response to Boiling Histotripsy is Prognostic for Intratumoral Immune Activation

open access: yesAdvanced Science, EarlyView.
Boiling Histrotripsy (BH), a mechanical form of focused ultrasound (FUS), allows for non‐invasive and non‐ionizing tissue destruction. Utilizing a BH treatment protocol that yielded bifurcating primary tumor growth responses, we found that immediate BH‐induced tumor growth control identifies tumors with acute reductions in antigen‐presenting cells (APC)
Lydia E. Kitelinger   +8 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

Human Foetal Neuroblasts Exhibit BK Channel‐Dependent Membrane Voltage Oscillations upon Depolarization

open access: yesAdvanced Science, EarlyView.
Primary cultures of neuroblasts isolated from the nucleus basalis of Meynert of 12‐weeks‐old human foetuses were prepared. Whole‐cell patch‐clamp recordings were performed by injecting a depolarizing stimulus current (+500 pA; 500 ms), and the membrane voltage recorded; this stimulus current evoked periodic‐like oscillations in membrane voltage ...
Elisabetta Coppi   +9 more
wiley   +1 more source

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