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Local Inflammation Precedes Diaphragm Wasting and Fibrotic Remodelling in a Mouse Model of Pancreatic Cancer.
J Cachexia Sarcopenia Muscle
February 2025
Department of Physical Therapy, University of Florida Health Cancer Center, Gainesville, Florida, USA.
Background: Cancer cachexia represents a debilitating muscle wasting condition that is highly prevalent in gastrointestinal cancers, including pancreatic ductal adenocarcinoma (PDAC). Cachexia is estimated to contribute to ~30% of cancer-related deaths, with deterioration of respiratory muscles suspected to be a key contributor to cachexia-associated morbidity and mortality. In recent studies, we identified fibrotic remodelling of respiratory accessory muscles as a key feature of human PDAC cachexia.
View Article and Find Full Text PDFObesity-associated MRAP2 variants impair multiple MC4R-mediated signaling pathways.
Hum Mol Genet
January 2025
Department of Metabolism and Systems Science, University of Birmingham, Birmingham, B15 2TT, United Kingdom.
The melanocortin-4 receptor (MC4R) is a G protein-coupled receptor expressed at hypothalamic neurons that has an important role in appetite suppression and food intake. Mutations in MC4R are the most common cause of monogenic obesity and can affect multiple signaling pathways including Gs-cAMP, Gq, ERK1/2, β-arrestin recruitment, internalization and cell surface expression. The melanocortin-2 receptor accessory protein 2 (MRAP2), is a single-pass transmembrane protein that interacts with and regulates signaling by MC4R.
View Article and Find Full Text PDFMolecular Dynamics Simulation for Membrane Fusion.
Methods Mol Biol
January 2025
Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
The soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) protein complex drives membrane fusion, and this process is further aided by accessory proteins, including complexin and α-synuclein. To understand the molecular mechanism underlying membrane fusion, we introduce an all-atom molecular dynamics (MD) simulation method. This method is used to understand and predict the conformations of protein and lipids, membrane geometry, and their interaction at femtosecond precision, by describing complex chemical systems with atomic models.
View Article and Find Full Text PDFHIV capsids: orchestrators of innate immune evasion, pathogenesis and pandemicity.
J Gen Virol
January 2025
Division of Infection and Immunity, UCL, London, WC1E 6BT, UK.
Human immunodeficiency virus (HIV) is an exemplar virus, still the most studied and best understood and a model for mechanisms of viral replication, immune evasion and pathogenesis. In this review, we consider the earliest stages of HIV infection from transport of the virion contents through the cytoplasm to integration of the viral genome into host chromatin. We present a holistic model for the virus-host interaction during this pivotal stage of infection.
View Article and Find Full Text PDFNovel genomic features in entomopathogenic fungus Beauveria bassiana ILB308: accessory genomic regions and putative virulence genes involved in the infection process of soybean pest Piezodorus guildinii.
Pest Manag Sci
January 2025
Laboratorio de Bioproducción, Bioinsumos, INIA Las Brujas, Canelones, Uruguay.
Background: Biological control methods involving entomopathogenic fungi like Beauveria bassiana have been shown to be a valuable approach in integrated pest management as an environmentally friendly alternative to control pests and pathogens. Identifying genetic determinants of pathogenicity in B. bassiana is instrumental for enhancing its virulence against insects like the resistant soybean pest Piezodorus guildinii.
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