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Structural insights into binding-site access and ligand recognition by human ABCB1.
EMBO J
January 2025
The Hormel Institute, University of Minnesota, Austin, MN, 55912, USA.
ABCB1 is a broad-spectrum efflux pump central to cellular drug handling and multidrug resistance in humans. However, how it is able to recognize and transport a wide range of diverse substrates remains poorly understood. Here we present cryo-EM structures of lipid-embedded human ABCB1 in conformationally distinct apo-, substrate-bound, inhibitor-bound, and nucleotide-trapped states at 3.
View Article and Find Full Text PDFLifetime risk and projected burden of dementia.
Nat Med
January 2025
Optimal Aging Institute and Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA.
Understanding the lifetime risk of dementia can inform public health planning and improve patient engagement in prevention. Using data from a community-based, prospective cohort study (n = 15,043; 26.9% Black race, 55.
View Article and Find Full Text PDFImportance: Cardiovascular health outcomes associated with noncigarette tobacco products (cigar, pipe, and smokeless tobacco) remain unclear, yet such data are required for evidence-based regulation.
Objective: To investigate the association of noncigarette tobacco products with cardiovascular health outcomes.
Design, Setting, And Participants: This cohort study was conducted within the Cross Cohort Collaboration Tobacco Working Group by harmonizing tobacco-related data and conducting a pooled analysis from 15 US-based prospective cohorts with data on the use of at least 1 noncigarette tobacco product ranging between 1948 and 2015.
Five-Year Results With Patisiran for Hereditary Transthyretin Amyloidosis With Polyneuropathy: A Randomized Clinical Trial With Open-Label Extension.
JAMA Neurol
January 2025
Amyloidosis Research and Treatment Center, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy.
Importance: There is a lack of long-term efficacy and safety data on hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN) and on RNA interference (RNAi) therapeutics in general. This study presents the longest-term data to date on patisiran for hATTR-PN.
Objective: To present the long-term efficacy and safety of patisiran in adults with hATTR-PN.
Effect of Triheptanoin on Caudate Atrophy and Motor Scores in Patients With Early-Stage Huntington Disease: A Phase II Study.
Neurology
January 2025
APHP- Salpêtrière Hospital, DMU BioGem, CNRS, INSERM, Paris Brain Institute, Sorbonne University.
Background And Objectives: Brain energy deficiency occurs at the early stage of Huntington disease (HD). Triheptanoin, a drug that targets the Krebs cycle, can restore a normal brain energetic profile in patients with HD. In this study, we aimed at assessing its efficacy on clinical and neuroimaging structural measures in HD.
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