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Recent studies revealed that the YTHDF family proteins bind preferentially to the N6-methyladenosine (m6A)-modified mRNA and regulate functions of these RNAs in different cell types. YTHDF2, the first identified m6A reader in mammals, has garnered significant attention because of its profound effect to regulate the m6A epitranscriptome in multiple biological processes. Here, we review current knowledge on the mechanisms by which YTHDF2 exerts its functions and discuss recent advances that underscore the multifaceted role of YTHDF2 in development, stem cell expansion and immune evasion.
View Article and Find Full Text PDFSP140 represses specific loci by recruiting polycomb repressive complex 2 and NuRD complex.
Nucleic Acids Res
December 2024
IFOM ETS, The AIRC Institute of Molecular Oncology, Via Adamello 16, 16039 Milano, Italy.
SP140, a lymphocytic-restricted protein, is an epigenetic reader working as a corepressor of genes implicated in inflammation and orchestrating macrophage transcriptional programs to maintain cellular identity. Reduced SP140 expression is associated both to autoimmune diseases and blood cancers. However, the molecular mechanisms that link SP140 altered protein levels to detrimental effects on the immune response and cellular growth, as well as the interactors through which SP140 promotes gene silencing, remain elusive.
View Article and Find Full Text PDFNeoadjuvant Chemotherapy VI-RADS Scores for Assessing Muscle-invasive Bladder Cancer Response to Neoadjuvant Immunotherapy with Multiparametric MRI.
Radiology
December 2024
From the Departments of Radiology (G. Brembilla, M.C., A.D.P., T.R., R.P., S.L., F.D.C.), Urology (G. Basile, M.B., M.M., A.B., F.M.), and Medical Oncology (D.R., C.M., V.T., A.C., D.P., E.C., A.N.), IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Via Olgettina 58, 20132 Milan, Italy (G. Brembilla, G. Basile, M.C., T.R., R.P., D.P., E.C., M.B., M.M., A.B., F.M., A.N., F.D.C.); Division of Surgery and Interventional Science, University College London, London, United Kingdom (F.G.); Department of Radiology, University College London Hospital NHS Foundation Trust, London, United Kingdom (F.G.); Genitourinary Department, Programma Prostata (P.G.) and Department of Radiology (A. Messina, G. Calareso), Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Urology, University of Texas MD Anderson Cancer Center, Houston, Tex (A. Martini); and Department of Radiology, IRCCS Ospedale San Raffaele-Turro, Milan, Italy (G. Cardone).
Background An accurate method of assessing the response of muscle-invasive bladder cancer (MIBC) to neoadjuvant treatment is needed for selecting candidates for bladder-sparing strategies. Purpose To evaluate the diagnostic accuracy and reproducibility of neoadjuvant chemotherapy Vesical Imaging Reporting and Data System (nacVI-RADS) scores and posttreatment Vesical Imaging Reporting and Data System (VI-RADS) scores when assessing MIBC response to neoadjuvant immunotherapy with multiparametric MRI (mpMRI). Materials and Methods A retrospective analysis of MRI scans was conducted in patients enrolled in the PURE-01 study (NCT02736266) from February 2017 to December 2019 who underwent pre- and postimmunotherapy mpMRI before radical cystectomy.
View Article and Find Full Text PDFRationalizing the effects of RNA modifications on protein interactions.
Mol Ther Nucleic Acids
December 2024
Centre for Human Technologies (CHT), RNA System Biology Lab, Istituto Italiano di Tecnologia (IIT), Via Enrico Melen, 83, 16152 Genova, Italy.
RNA modifications play a crucial role in regulating gene expression by altering RNA structure and modulating interactions with RNA-binding proteins (RBPs). In this study, we explore the impact of specific RNA chemical modifications-N-methyladenosine (m⁶A), A-to-I editing, and pseudouridine (Ψ)-on RNA secondary structure and protein-RNA interactions. Utilizing genome-wide data, including RNA secondary structure predictions and protein-RNA interaction datasets, we classify proteins into distinct categories based on their binding behaviors: modification specific and structure independent, or modification unspecific and structure dependent.
View Article and Find Full Text PDFBRD4 inhibition rewires cardiac macrophages toward a protective phenotype marked by low MHC class II expression.
Am J Physiol Heart Circ Physiol
December 2024
Department of Medicine, Division of Cardiology, University of Colorado Anschutz Medical Campus; Aurora, CO, USA.
Bromodomain and extra-terminal domain (BET) proteins, including BRD4, bind acetylated chromatin and co-activate gene transcription. A BET inhibitor, JQ1, prevents and reverses pathological cardiac remodeling in preclinical models of heart failure. However, the underlying cellular mechanisms by which JQ1 improves cardiac structure and function remain poorly defined.
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