Results 61 to 70 of about 27,247 (245)

Phenotyping of Rare CFTR Mutations Reveals Distinct Trafficking and Functional Defects

Cells, 2020
Background. The most common CFTR mutation, F508del, presents with multiple cellular defects. However, the possible multiple defects caused by many rarer CFTR mutations are not well studied.
Marjolein Ensinck, Liesbeth De Keersmaecker, Lise Heylen, Anabela S. Ramalho, Rik Gijsbers, Ricard Farré, Kris De Boeck, Frauke Christ, Zeger Debyser, Marianne S. Carlon   +9 more
doaj   +1 more source

Rescue of Mutant CFTR Trafficking Defect by the Investigational Compound MCG1516A

Cells, 2022
Although some therapeutic progress has been achieved in developing small molecules that correct F508del-CFTR defects, the mechanism of action (MoA) of these compounds remain poorly elucidated.
Miquéias Lopes-Pacheco, Mafalda Bacalhau, Sofia S. Ramalho, Iris A. L. Silva, Filipa C. Ferreira, Graeme W. Carlile, David Y. Thomas, Carlos M. Farinha, John W. Hanrahan, Margarida D. Amaral   +9 more
doaj   +1 more source

A Unifying Thermodynamic Model for Phase Separation and Aging of Biopolymers

Advanced 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, Joana Caria, Edward A. Lemke   +2 more
wiley   +1 more source

Female rats are less susceptible during puberty to the lethal effects of percutaneous exposure to VX

Toxicology Reports, 2016
Nerve agents with low volatility such as VX are primarily absorbed through the skin when released during combat or a terrorist attack. The barrier function of the stratum corneum may be compromised during certain stages of development, allowing VX to ...
Linnzi K.M. Wright, Robyn B. Lee, Edward D. Clarkson, Lucille A. Lumley   +3 more
doaj   +1 more source

Corr-4a reverses the negative effects of VX-770 on VX-809-corrected ΔF508 CFTR half-life.

, 2016
A. I507-ATT ΔF508 CFTR turnover in VX-809 (5μM), VX-809+VX-770 (5μM+5μM) and VX-809+VX-770+Corr-4a (5μM +5μM+10μM) treated cells. B. I507-ATC ΔF508 CFTR turnover in VX-809 (5μM), VX-809+VX-770 (5μM+5μM) and VX-809+VX-770+Corr-4a (5μM +5μM+10μM) treated ...
Purushotham Guroji (2805343), Ahmed Lazrak (613734), Sadis Matalon (613735), Vedrana Bali (2805340), Zsuzsanna Bebok (2657035)   +4 more
core   +1 more source

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

Advanced 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, Yu He, Shuyao Li, Haoyu Guan, Ruili Cui, Yu Shi, Zhongwen Jiang, Siyu Wang, Xuan Li, Jiyuan Li, Mei Hu, Yupeng Zhou, Beisha Tang, Yanyan Zhang, Zhaobing Gao, Yu Zhou, Zhenhua Liu, Ping Li   +17 more
wiley   +1 more source

The Functional Impact of VX-770 on the Cystic Fibrosis Transmembrane Conductance Regulator Is Enduring and Increases the Constitutive Activity of This Channel in Primary Airway Epithelia Generated from Healthy Donors

Biomolecules
VX-770 is a small-molecule CFTR potentiator that is highly efficacious in individuals with cystic fibrosis caused by mutations in CFTR that result in a defect in channel gating.
Heidi J. Nick, Sarah E. Christeson, Preston E. Bratcher   +2 more
doaj   +1 more source

A High‐Loading Zn Single‐Atom Nanozyme Targets the Zn/HIF‐1α/GLUT1 Axis to Disrupt Glucose Metabolic Reprogramming and Remodel the Tumor Immune Microenvironment

Advanced Science, EarlyView.
A high‐loading Zn single‐atom nanozyme (ZMG@CS) delivers ML‐SA5 and GOx to lysosomes. ML‐SA5 activates TRPML1 to release endogenous Zn2+, while the nanozyme provides exogenous Zn2+ and GOx‐driven acidification amplifies ROS production. Together, these effects suppress the HIF‐1α/GLUT1 axis, disrupt glucose and redox homeostasis, induce disulfidptosis ...
Zhenxin Wang, Yuhang Tang, Ronghao Yue, Jingtao Xu, Yong Tao, Jie Chen, Shipeng Li, Guosheng Zhao, Jinfang Xue, Mingwei Sun, Fenglei Gao, Yunsheng Ou, Yang Wang   +12 more
wiley   +1 more source

The Development and Characterization of VX-770 Molecular Probes [PDF]

, 2016
Cystic fibrosis is the most common genetic disease affecting the Canadian population. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene, and there is currently no cure.
Hung, Maurita
core   +2 more sources

Stress Hyperglycemia Drives CD4+ T Cell PANoptosis and Postoperative Organ Injury via Monocyte‐Derived Succinate

Advanced Science, EarlyView.
High glucose is linked to reduced succinate dehydrogenase activity in CD14+ monocytes, accompanied by succinate accumulation and extracellular release. Extracellular succinate exacerbates mitochondrial ROS production and mtDNA release in CD4+ T cells. Cytosolic mtDNA then activates Z‐DNA binding protein 1 (ZBP1) and engages ZBP1‐associated inflammatory
Shuai Zhao, Xuemei Miao, Wei Luo, Tao Liu, Yang Wang, Jiaying Li, Di Fu, Weiyun Shen, Yan Luo, Kang Chen, Ruping Dai, Hui Li   +11 more
wiley   +1 more source