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Short-chain fatty acid metabolites propionate and butyrate are unique epigenetic regulatory elements linking diet, metabolism and gene expression.
Nat Metab
January 2025
Department of Genetics, Stanford University, School of Medicine, Stanford, CA, USA.
The short-chain fatty acids (SCFAs) propionate and butyrate have beneficial health effects, are produced in large amounts by microbial metabolism and have been identified as unique acyl lysine histone marks. To better understand the function of these modifications, we used chromatin immunoprecipitation followed by sequencing to map the genome-wide location of four short-chain acyl histone marks, H3K18pr, H3K18bu, H4K12pr and H4K12bu, in treated and untreated colorectal cancer (CRC) and normal cells as well as in mouse intestines in vivo. We correlate these marks with open chromatin regions and gene expression to access the function of the target regions.
View Article and Find Full Text PDFRibosome customization and functional diversification among P-stalk proteins regulate late poxvirus protein synthesis.
Cell Rep
January 2025
Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. Electronic address:
Growing evidence suggests that ribosomes selectively regulate translation of specific mRNA subsets. Here, quantitative proteomics and cryoelectron microscopy demonstrate that poxvirus infection does not alter ribosomal subunit protein (RP) composition but skews 40S rotation states and displaces the 40S head domain. Genetic knockout screens employing metabolic assays and a dual-reporter virus further identified two RPs that selectively regulate non-canonical translation of late poxvirus mRNAs, which contain unusual 5' poly(A) leaders: receptor of activated C kinase 1 (RACK1) and RPLP2.
View Article and Find Full Text PDFBackground: Changes in Amyloid-β (A) and hyperphosphorylated Tau (T) in the brain and cerebrospinal fluid (CSF) precedes AD symptoms, making the CSF proteome a potential avenue to understand disease pathophysiology and facilitate reliable diagnostics and therapies.
Method: We used the Somascan assay for measuring the protein levels of 7,029 analytes in CSF of 2,286 participants from four different cohorts. We employed a three-stage analytical approach (discovery, replication, and meta-analysis).
Biomarkers.
Alzheimers Dement
December 2024
Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Background: The identification of novel blood-based biomarkers of small vessel disease of the brain (SVD) may improve pathophysiologic understanding and inform the development of new therapeutic strategies for prevention. We evaluated plasma proteomic associations of white matter fractional anisotropy (WMFA), white matter hyperintensity (WMH) volume, enlarged perivascular space (ePVS) volume, and the presence of microbleeds (MB) on brain magnetic resonance imaging (MRI) in the population-based Multi-Ethnic Study of Atherosclerosis (MESA).
Methods: Eligible MESA participants had 2941 plasma proteins measured from stored blood samples (collected in 2016-2018) using the antibody-based Olink proteomics platform, and completed brain MRI scans in 2018-2019.
Developing Topics.
Alzheimers Dement
December 2024
NeuroGenomics & Informatics Center, Washington University School of Medicine, St. Louis, MO, USA.
Background: Cerebrospinal fluid (CSF) is a valuable resource for the study and diagnosis of neurological diseases, but few studies have comprehensively characterized the genetic determinants of CSF protein levels that may contribute to the development of disease. These quantitative trait loci (QTL) have proven vital to identifying candidate genes for disease treatment and monitoring. Here, we utilize our largest-to-date CSF protein QTL atlas to prioritize potentially causal proteins for 14 neurological traits and examine the unique and overlapping disease mechanisms observed using CSF proteins.
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