The cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel consists of two motifs (each containing a membrane-spanning domain [MSD] and a nucleotide-binding domain [NBD]) linked by an R domain. We tested the hypothesis that one MSD-NBD motif could form a Cl- channel. The amino-terminal portion of CFTR (D836X, which contains MSD1, NBD1, and the R domain) formed Cl- channels with conductive properties identical to those of CFTR. However, channel regulation differed. Although phosphorylation increased activity, channels opened without phosphorylation. MgATP stimulated D836X more potently than CFTR and may interact at more than one site. These data and migration of D836X on sucrose density gradients suggest that D836X may function as a multimer. Thus, the amino-terminal portion of CFTR contains all of the structures required to build a regulated Cl- channel.
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http://dx.doi.org/10.1016/0092-8674(94)90385-9 | DOI Listing |
Background: Understanding the genetic etiology of Alzheimer's disease (AD) has been a major focus of research in neurodegenerative diseases. Amid the three common allelic variants of the apolipoprotein E (APOE) gene in humans, called APOE ε2, ε3 and ε4, the ε4 allele is the most common genetic risk factor for late-onset AD, being found in 20% of the world population.
Method: We used Event-Related Potentials (ERP) and Event-Related Spectral Perturbation (ERSP) as features for classification of apolipoprotein E ϵ4 (APOE ε4) allele carriers in AD patients and healthy controls.
Background: Cerebral microbleeds (CMBs) hold significant clinical relevance, linked to elevated risks of hemorrhages, cognitive decline, and mortality. Notably, with the recent advancement in Alzheimer's treatments, the number of CMBs serves as a crucial safety indicators to assess the risk and occurrence of amyloid-related imaging abnormalities. However, the commonly utilized manual detection process is time-consuming and labor-intensive, prompting the development of various automated detection models.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Centre for Brain Research (CBR), Indian Institute of Science, Bengaluru, Karnataka, India.
Background: Deep Neural Networks (DNNs) have emerged as powerful tools in the biomedical field, particularly for the early detection of neurodegenerative diseases. Despite their complexity and data-intensive nature, simpler fully connected Convolutional Neural Network (SFCN) architectures have shown effectiveness in accurately discerning between subjects affected by Alzheimer's disease (AD) and healthy controls (HC). This model draws inspiration from the work of Peng H et al.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Health Sciences and Pharmacy, St. Louis, MO, USA.
Background: Major Depressive Disorder (MDD) is a complex and multifaceted condition. Traditional screening methods may not capture the full spectrum of symptoms, causing delayed diagnoses or misdiagnoses. Further, MDD is highly prevalent among patients with mild cognitive impairment (MCI), which may then progress to Alzheimer's disease (AD).
View Article and Find Full Text PDFJCI Insight
January 2025
Center for Precision Medicine, Department of Medicine, and.
The role played by anionic channels in diabetic kidney disease (DKD) is not known. Chloride channel accessory 1 (CLCA1) facilitates the activity of TMEM16A (Anoctamin-1), a Ca2+-dependent Cl- channel. We examined if CLCA1/TMEM16A had a role in DKD.
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