The horizontal transfer of plasmids has been recognized as one of the key drivers for the worldwide spread of antimicrobial resistance (AMR) across bacterial pathogens. However, knowledge remain limited about the contribution made by environmental stress on the evolution of bacterial AMR by modulating horizontal acquisition of AMR plasmids and other mobile genetic elements. Here we combined experimental evolution, whole genome sequencing, reverse genetic engineering, and transcriptomics to examine if the evolution of chromosomal AMR to triclosan (TCS) disinfectant has correlated effects on modulating bacterial pathogen (Klebsiella pneumoniae) permissiveness to AMR plasmids and phage susceptibility.
View Article and Find Full Text PDFIdentification of branched-chain amino acid (BCAA) oxidation enzymes in the nucleus led us to predict that they are a source of the propionyl-CoA that is utilized for histone propionylation and, thereby, regulate gene expression. To investigate the effects of BCAAs on the development of cardiac hypertrophy and failure, we applied pressure overload on the heart in mice maintained on a diet with standard levels of BCAAs (BCAA control) versus a BCAA-free diet. The former was associated with an increase in histone H3K23-propionyl (H3K23Pr) at the promoters of upregulated genes (e.
View Article and Find Full Text PDFTraditional medicine, 'LuRu', is a commonly used Tibetan medicine for clearing away heat and detoxifying. Dried products of and are often used as 'LuRu' in the market. This study aims to compare the chemical constituents of and using GC-MS and UPLC-TOF-MS, and confirm which plant species is more suitable to be used as 'LuRu'.
View Article and Find Full Text PDFCa/Fe-rich antibiotic fermentation residues (AFRs), a type of hazardous waste, can be regarded as recyclable biomass and metal resources. However, concurrent detoxification and reutilization of biomass and metals resources from AFRs have never been reported before. In this study, Ca/Fe-rich vancomycin fermentation residues were pyrolyzed into biochar to adsorb phosphate for the first time.
View Article and Find Full Text PDFIn this study, a novel and low-cost seawater-modified biochar (SBC) was fabricated via the pyrolysis of fir wood waste followed by co-precipitation modification using seawater as the Ca/Mg source. The co-precipitation pH was a vital factor during modification, and the optimal pH was 10.50 according to calculations using PHREEQC 2.
View Article and Find Full Text PDFObjective: We previously reported that β-oxidation enzymes are present in the nucleus in close proximity to transcriptionally active promoters. Thus, we hypothesized that the fatty acid intermediate, butyryl-CoA, is the substrate for histone butyrylation and its abundance is regulated by acyl-CoA dehydrogenase short chain (ACADS). The objective of this study was to determine the genomic distribution of H3K9-butyryl (H3K9Bu) and its regulation by dietary fat, stress, and ACADS and its impact on gene expression.
View Article and Find Full Text PDFAdiponectin is one of the most abundant circulating hormones, which through adenosine monophosphate-activated protein kinase (AMPK), enhances fatty acid and glucose oxidation, and exerts a cardioprotective effect. However, its effects on cellular bioenergetics have not been explored. We have previously reported that 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR, an AMPK activator) enhances mitochondrial respiration through a succinate dehydrogenase (SDH or complex II)-dependent mechanism in cardiac myocytes, leading us to predict that Adiponectin would exert a similar effect via activating AMPK.
View Article and Find Full Text PDFBiochim Biophys Acta Gene Regul Mech
October 2019
Histone H2A.Z plays an essential role in regulating transcriptional rates and memory. Interestingly, H2A.
View Article and Find Full Text PDFBiochim Biophys Acta Gene Regul Mech
May 2018
The mechanisms that regulate H2A.Z and its requirement for transcription in differentiated mammalian cells remains ambiguous. In this study, we identified the interaction between the C-terminus of ANP32e and N-terminus of H2A.
View Article and Find Full Text PDFBackground: MicroRNAs (miR) are small, posttranscriptional regulators, expressed as part of a longer primary transcript, following which they undergo nuclear and cytoplasmic processing by Drosha and Dicer, respectively, to form the functional mature ~20mer that gets incorporated into the silencing complex. Others and we have shown that mature miR-1 levels decrease with pressure-induced cardiac hypertrophy, however, there is little or no change in the primary transcript encompassing miR-1 stem-loop, suggesting critical regulatory step in microRNA processing. The objective of this study was to investigate the underlying mechanisms regulating miR-1 expression in cardiomyocytes.
View Article and Find Full Text PDFBackground: We previously reported that specialized and housekeeping genes are differentially regulated via de novo recruitment and pause-release of RNA polymerase II, respectively, during cardiac hypertrophy. However, the significance of this finding remains to be examined. Therefore, the purpose of this study was to determine the mechanisms that differentially regulate these gene groups and exploit them for therapeutic targeting.
View Article and Find Full Text PDFCardiac hypertrophy is characterized by a generalized increase in gene expression that is commensurate with the increase in myocyte size and mass, on which is superimposed more robust changes in the expression of specialized genes. Both transcriptional and posttranscriptional mechanisms play fundamental roles in these processes; however, genome-wide characterization of the transcriptional changes has not been investigated. Our goal was to identify the extent and modes, RNA polymerase II (pol II) pausing versus recruitment, of transcriptional regulation underlying cardiac hypertrophy.
View Article and Find Full Text PDFAims: GATA4 is a transcription factor that is up-regulated during cardiac hypertrophy and plays a fundamental role in myocyte growth and survival. In this study, we investigate the transcriptional vs. post-transcriptional mechanisms that are involved in regulating GATA4 in the heart during neonatal and pressure overload-induced hypertrophic growth.
View Article and Find Full Text PDFMicroRNA-21 (miR-21) is highly up-regulated during hypertrophic and cancerous cell growth. In contrast, we found that it declines in cardiac myocytes upon exposure to hypoxia. Thus, the objective was to explore its role during hypoxia.
View Article and Find Full Text PDFWe have recently reported that downregulation of miR-199a-5p is necessary and sufficient for inducing upregulation of its targets, including hypoxia-inducible factor-1 alpha (Hif-1 alpha) and Sirt1, during hypoxia preconditioning (HPC). Conversely, others and we have reported that miR-199a-5p is upregulated during cardiac hypertrophy. Thus, the objective of this study was to delineate the signaling pathways that regulate the expression of miR-199a-5p and its targets, and their role in myocyte survival during hypoxia.
View Article and Find Full Text PDFMicroRNAs are posttranscriptional gene regulators that are differentially expressed during various diseases and have been implicated in the underlying pathogenesis. We report here that miR-199a is acutely downregulated in cardiac myocytes on a decline in oxygen tension. This reduction is required for the rapid upregulation of its target, hypoxia-inducible factor (Hif)-1alpha.
View Article and Find Full Text PDFThe posttranscriptional regulator, microRNA-21 (miR-21), is up-regulated in many forms of cancer, as well as during cardiac hypertrophic growth. To understand its role, we overexpressed it in cardiocytes where it revealed a unique type of cell-to-cell "linker" in the form of long slender outgrowths and branches. We subsequently confirmed that miR-21 directly targets and down-regulates the expression of Sprouty2 (SPRY2), an inhibitor of branching morphogenesis and neurite outgrowths.
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