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| http://dx.doi.org/10.1007/s10565-019-09505-4 | DOI Listing |
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Defining proteoform-specific interactions for drug targeting in a native cell signalling environment.
Nat Chem
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Physical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, Oxford, UK.
Understanding the dynamics of membrane protein-ligand interactions within a native lipid bilayer is a major goal for drug discovery. Typically, cell-based assays are used, however, they are often blind to the effects of protein modifications. In this study, using the archetypal G protein-coupled receptor rhodopsin, we found that the receptor and its effectors can be released directly from retina rod disc membranes using infrared irradiation in a mass spectrometer.
View Article and Find Full Text PDFDifferentiation of the chronic lymphocytic leukemia response to ibrutinib and acalabrutinib treatment by single-cell MALDI-TOF MS imaging.
J Pharm Biomed Anal
January 2025
Clinical Institute of Laboratory Diagnostics, University Hospital Centre Osijek, J. Huttlera 4, Osijek 31 000, Croatia; Faculty of Medicine Osijek, JJ Strossmayer University of Osijek, J. Huttlera 4, Osijek 31 000, Croatia. Electronic address:
Ibrutinib and acalabrutinib, Bruton's tyrosine kinase inhibitors (BTKi) used for chronic lymphocytic leukemia (CLL) treatment, aim the same target but their off-target effects are different. The aim of this study was to use single-cell MALDI TOF mass spectrometry imaging to compare the CD19+ lymphocytes' mass spectra in untreated and ibrutinib- or acalabrutinib-treated subjects in order to better understand the therapeutic effect of BTKi. 180 cells from 9 male subjects divided in 3 groups (untreated, ibrutinib-treated and acalabrutinib-treated) were analyzed using MALDI-TOF mass spectrometry analyzer.
View Article and Find Full Text PDFxCas9 is an evolved variant of the CRISPR-Cas9 genome editing system, engineered to improve specificity and reduce undesired off-target effects. How xCas9 expands the DNA targeting capability of Cas9 by recognizing a series of alternative Protospacer Adjacent Motif (PAM) sequences while ignoring others is unknown. Here, we elucidate the molecular mechanism underlying xCas9's expanded PAM recognition and provide critical insights for expanding DNA targeting.
View Article and Find Full Text PDFGene expression is coordinated by a multitude of transcription factors (TFs), whose binding to the genome is directed through multiple interconnected epigenetic signals, including chromatin accessibility and histone modifications. These complex networks have been shown to be disrupted during aging, disease, and cancer. However, profiling these networks across diverse cell types and states has been limited due to the technical constraints of existing methods for mapping DNA:Protein interactions in single cells.
View Article and Find Full Text PDFPara-aminopropiophenone toxicity in domestic dogs: a description of non-target toxicosis in Victoria, Australia: 13 dogs (2016-2023).
Aust Vet J
January 2025
Melbourne Veterinary School, University of Melbourne, Werribee, Victoria, Australia.
Background: PAPP is widely used in Australia as a potent vertebrate bait, with potential for off-target ingestion and poisoning in domestic dogs. Whilst toxicosis and resulting methaemoglobinaemia is anecdotally known to occur, this is the first description in the literature. This study reports thirteen clinical cases of suspected Para-aminopropiophenone (PAPP) toxicity in dogs, with the aim of describing clinical presentation and current management of toxicosis in this species.
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