The factors that determine persistence or clearance of hepatitis C virus (HCV) infection are poorly understood. The CD4 T cell responses to the HCV core protein were examined in a cohort of women infected with a single genotype of HCV. CD4 T cells from HCV-infected patients secreted interferon (IFN)-gamma in response to peptides from 4 immunodominant regions of the core protein, and these responses were stronger in persistently infected women. Interleukin (IL)-10 was also produced by CD4 T cells from HCV-infected subjects in response to the same core peptides. Furthermore, HCV core-specific CD4 T cell clones secreted either IFN-gamma or IL-10 but not IL-4. These findings demonstrate that T helper type 1 and regulatory T cells are induced against the same epitopes on the core protein during HCV infection.
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http://dx.doi.org/10.1086/339340 | DOI Listing |
New Phytol
January 2025
Section for Plant Biochemistry and Copenhagen Plant Science Centre, Department of Plant and Environmental Sciences, University of Copenhagen, 1871, Frederiksberg, Denmark.
Lupins are promising protein crops that accumulate toxic quinolizidine alkaloids (QAs) in the seeds, complicating their end-use. QAs are synthesized in green organs (leaves, stems, and pods) and a subset of them is transported to the seeds during fruit development. The exact sites of biosynthesis and accumulation remain unknown; however, mesophyll cells have been proposed as sources, and epidermal cells as sinks.
View Article and Find Full Text PDFBrain Behav Immun Health
February 2025
Healthy Brain Ageing Program, Brain and Mind Centre, School of Psychology, Faculty of Science, University of Sydney, NSW, 2050, Australia.
Inflammation is becoming increasingly recognised as a core feature of dementia with evidence indicating that its role may vary and adapt across different stages of the neurodegenerative process. This study aimed to investigate whether the associations of high-sensitivity C-reactive protein (hs-CRP) with neuropsychological performance (verbal memory, executive function, processing speed) and cerebral white matter hyperintensities (WMHs) differed between older adults with subjective cognitive decline (SCD; = 179) and mild cognitive impairment (MCI; = 286). Fasting serum hs-CRP concentrations were grouped into low (<1.
View Article and Find Full Text PDFJ Appl Toxicol
January 2025
Department of Toxicology, School of Public Health, Jilin University, Changchun, China.
Cadmium (Cd) is a widely available metal that has been found to have a role in causing nonalcoholic fatty liver disease (NAFLD). However, the detailed toxicological targets and mechanisms by which Cd causes NAFLD are unknown. Therefore, the present work aims to reveal the main targets of action, cellular processes, and molecular pathways by which cadmium causes NAFLD.
View Article and Find Full Text PDFJ Cheminform
January 2025
Oxford Protein Informatics Group, Department of Statistics, University of Oxford, Oxford, UK.
Current strategies centred on either merging or linking initial hits from fragment-based drug design (FBDD) crystallographic screens generally do not fully leaverage 3D structural information. We show that an algorithmic approach (Fragmenstein) that 'stitches' the ligand atoms from this structural information together can provide more accurate and reliable predictions for protein-ligand complex conformation than general methods such as pharmacophore-constrained docking. This approach works under the assumption of conserved binding: when a larger molecule is designed containing the initial fragment hit, the common substructure between the two will adopt the same binding mode.
View Article and Find Full Text PDFMethods Mol Biol
January 2025
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, USA.
Many membrane proteins on the cell surface are constantly internalized from, and re-delivered to, the plasma membrane. This endocytic cycling, which relies on accurate SNARE-mediated fusion of vesicles containing cargo proteins, is highly important for the function of many proteins such as signaling receptors. While the SNARE proteins that mediate fusion during specific events, such as neurotransmitter and hormone release, in mammalian cells has been heavily studied, the SNARE proteins that mediate surface delivery of specific cargo such as the receptors for these released factors are still not known.
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