Project description:We aim to compare the genomic discrepancies across de novo Ph+ ALL, Ph+ MPAL and Ph+ AML, three diseases characterized by the occurrence of BCR-ABL1 transcripts but showing varied immunophenotypes. The data we are now submitting is the genomic copy number variants of these three groups. The following is the abstract with associated manuscript. The chromosome abnormality of Philadelphia (Ph) is typically seen in de novo acute lymphoblastic leukemia (ALL). It has also been identified in mixed phenotype acute leukemia (MPAL) and acute myeloid leukemia (AML) in the revisions to World Health Organization classification of myeloid neoplasms and actue leukemia. The discrepancies between these patients and potential mechanisms underlying differentiation fate of the leukemia cells remain poorly defined. We evaluated the clinical, genomic and transcriptomic features of Ph+ ALL, Ph+ MPAL and Ph+ AML by taking advantage of high-density genomic analysis, including next-generation sequencing array comparative genomic hybridization and gene expression profiling for transcriptomic analysis. Our results showed that the three cohorts demonstrated diversified clinical features. Ph+ ALL had the best response to induction therapy, with a complete remission (CR) rate of 93.5 and molecular response of 43.5%. Ph+ MPAL had a 90.0% CR rate but only 5.9% of molecular response. The CR rate of Ph+ AML was only 68.8%. Ph+ ALL was characterized by loss and mutations of B-cell development gene IKZF1 and PAX5, and frequent histone H3K36 trimethyltransferase SETD2 mutations. SETD2 mutations were detected in 11.3% of Ph+ ALL patients and predicted higher relapse rate. Ph+ MPAL and Ph+ AML featured high frequency of RUNX1 mutations. Further studies showed RUNX1-R177X mutation inhibited 32D cell differentiation induced by G-Csf, and cooperated with BCR-ABL1 to lead to myeloid differentiation arrest of human cord blood CD34+ cells. It is therefore presumed that these additional mutations work in synergy with BCR-ABL1 fusion gene to facilitate the development of Ph-positive acute leukemia in different immunophenotypic classifications.
Project description:Whole genome sequencing was performed on E. coli BL21 (DE3) evolved at 25°C in pH 9 terrific broth media buffered with Tris-HCl (pH 9). The evolved E. coli was characterized and compared to the parent strain.
Project description:Genomic evolution of Enterobacter hormaechei towards resistance in an osteoarticular infection under piperacillin/tazobactam treatment
Project description:Lipomyces genome scale model based on the Lipomyces starkeyi NRRL-11557 genome.
Published in:
Genome-Scale Model Development and Genomic Sequencing of the Oleaginous Clade Lipomyces
Frontiers in Bioengineering and Biotechnology
Industrial Biotechnology
Volume 12 - 2024 | doi: 10.3389/fbioe.2024.1356551
Project description:Differences in global levels of histone acetylation occur in normal and cancer cells, although the reason cells regulate these levels has remained unclear. Here we demonstrate a role for histone acetylation in regulating intracellular pH (pHi). As pHi decreases, histones are globally deacetylated by histone deacetylases (HDACs) and the released acetate anions are co-exported with protons out of the cell by monocarboxylate transporters (MCTs), preventing further reductions in pHi. Conversely, global histone acetylation increases at more alkaline pHi, such as when resting cells are induced to proliferate. Inhibition of HDACs or MCTs decreases acetate export and lowers pHi, particularly compromising pHi maintenance in acidic environments. Global deacetylation at low pH is reflected at a genomic level by decreased abundance and extensive redistribution of acetylation at promoters and intergenic regions. Thus acetylation of chromatin functions as a rheostat to regulate pHi with important implications for therapeutic use of HDAC inhibitors. To investigate the redistribution of H4K16ac throughout the genome upon treatment at pH 6.5
Project description:BackgroundCross-border healthcare may promote the spread of multidrug-resistant microorganisms (MDRO) and is challenging due to heterogeneous antimicrobial resistance (AMR) prevention measures (APM). The aim of this article is to compare healthcare workers (HCW) from Germany (DE) and The Netherlands (NL) on how they perceive and experience AMR and APM, which is important for safe patient exchange and effective cross-border APM cooperation.MethodsA survey was conducted amongst HCW (n = 574) in hospitals in DE (n = 305) and NL (n = 269), using an online self-administered survey between June 2017 and July 2018. Mann-Whitney U tests were used to analyse differences between answers of German and Dutch physicians (n = 177) and German and Dutch nurses (n = 397) on 5-point Likert Items and Scales.ResultsSimilarities between DE and NL were a high awareness about the AMR problem and the perception that the possibility to cope with AMR is limited (30% respondents perceive their contribution to limit AMR as insufficient). Especially Dutch nurses scored significantly lower than German nurses on their contribution to limit AMR (means 2.6 vs. 3.1, p ≤ 0.001). German HCW were more optimistic about their potential role in coping with AMR (p ≤ 0.001), and scored higher on feeling sufficiently equipped to perform APM (p ≤ 0.003), although the mean scores did not differ much between German and Dutch respondents.ConclusionsAlthough both German and Dutch HCW are aware of the AMR problem, they should be more empowered to contribute to limiting AMR through APM (i.e. screening diagnostics, infection diagnosis, treatment and infection control) in their daily working routines. The observed differences reflect differences in local, national and cross-border structures, and differences in needs of HCW, that need to be considered for safe patient exchange and effective cross-border APM.
Project description:Whole genome bisulfite sequencing was performed on Chromomethylase-2 and Dicer-like-3 knockout mutants in order to confirm the results from genome wide association mapping and to identify the respective genomic regions that they target. Bisulfite sequencing of knockout mutants and WT controls
Project description:BackgroundBacterial antimicrobial resistance (AMR) is a global threat to both humans and livestock. Despite this, there is limited global consensus on data-informed, priority areas for intervention in both sectors. We compare current livestock AMR data collection efforts with other variables pertinent to human and livestock AMR to identify critical data gaps and mutual priorities.MethodsWe globally synthesized livestock AMR data from open-source surveillance reports and point prevalence surveys stratified for six pathogens (Escherichia coli, Staphylococcus aureus, non-typhoidal Salmonella, Campylobacter spp., Enterococcus faecalis, Enterococcus faecium) and eleven antimicrobial classes important in human and veterinary use, published between 2000 and 2020. We also included all livestock species represented in the data: cattle, chickens, pigs, sheep, turkeys, ducks, horses, buffaloes, and goats. We compared this data with intended priorities calculated from: disability-adjusted life years (DALYs), livestock antimicrobial usage (AMU), livestock biomass, and a global correlation exercise between livestock and human proportion of resistant isolates.ResultsResistance to fluoroquinolones and macrolides in Staphylococcus aureus were identified as priorities in many countries but, less than 10% of these reported livestock AMR data. Resistance data for Escherichia coli specific to cattle, chickens, and pigs, which we prioritized, were also well collected. AMR data collection on non-typhoidal Salmonella and other livestock species were often not prioritized. Of 232 categories prioritized by at least one country, data were only collected for 48% (n = 112).ConclusionsThe lack of livestock AMR data globally for broad resistance in Staphylococcus aureus could underplay their zoonotic threat. Countries can bolster livestock AMR data collection, reporting, and intervention setting for Staphylococcus aureus as done for Escherichia coli. This framework can provide guidance on areas to strengthen AMR surveillance and decision-making for humans and livestock, and if done routinely, can adapt to resistance trends and priorities.