Rate-limiting step analysis of the microbial desulfurization of dibenzothiophene in a model oil system

A mechanistic analysis of the various mass transport and kinetic steps in the microbial desulfurization of dibenzothiophene (DBT) by Rhodococcus erythropolis IGTS8 in a model biphasic (oil–water), small-scale system was performed. The biocatalyst was distributed into three populations, free cells in the aqueous phase, cell aggregates and oil–adhered cells, and the fraction of cells in each population was measured. The power input per volume (P/V) and the impeller tip speed (v[subscript tip]) were identified as key operating parameters in determining whether the system is mass transport controlled or kinetically controlled. Oil–water DBT mass transport was found to not be limiting under the conditions tested. Experimental results at both the 100 mL and 4 L (bioreactor) scales suggest that agitation leading to P/V greater than 10,000 W/ m3 and/or v[subscript tip] greater than 0.67 m/s is sufficient to overcome the major mass transport limitation in the system, which was the diffusion of DBT within the biocatalyst aggregates.National Institutes of Health (U.S.). Biotechnology Training Program (Grant T32GM008334)Saudi Aramc

Dissimilatory Antimonate Reduction and Production of Antimony Trioxide Microcrystals by a Novel Microorganism

Antimony (Sb) is a metalloid that has been exploited by humans since the beginning of modern civilization. The importance of Sb to such diverse industries as nanotechnology and health is underscored by the fact that it is currently the ninth-most mined metal worldwide. Although its toxicity mirrors that of its Group 15 neighbor arsenic, its environmental chemistry is very different, and, unlike arsenic, relatively little is known about the fate and transport of Sb, especially with regard to biologically mediated redox reactions. To further our understanding of the interactions between microorganisms and Sb, we have isolated a bacterium that is capable of using antimonate [Sb­(V)] as a terminal electron acceptor for anaerobic respiration, resulting in the precipitation of antimonite [Sb­(III)] as microcrystals of antimony trioxide. The bacterium, designated strain MLFW-2, is a sporulating member of a deeply branching lineage within the order <i>Bacillales</i> (phylum <i>Firmicutes</i>). This report provides the first unequivocal evidence that a bacterium is capable of conserving energy for growth and reproduction from the reduction of antimonate. Moreover, microbiological antimonate reduction may serve as a novel route for the production of antimony trioxide microcrystals of commercial significance to the nanotechnology industry

The natural history of NPM1MUT Measurable Residual Disease (MRD) positivity after completion of chemotherapy in Acute Myeloid Leukemia (AML)

Molecular MRD assays targeting NPM1 mutant (mut) transcripts have an established role for monitoring treatment efficacy in patients with NPM1mut AML. Approximately 25% of NPM1mut patients show persistent MRD level in the bone marrow (BM) at the end of treatment (EOT), which is associated with a higher risk of relapse (Ivey, NEJM 2016; Kronke, JCO 2011). Molecular persistence at low copy number (MP-LCN) is defined by the European LeukemiaNet (ELN) as MRD positivity in patients in morphological complete remission (CR) with <1000-2000 transcripts per 105ABL and a relative increase of <1 log between any two positive samples collected after EOT (Schuurhuis, Blood 2018). The UK NCRI working group recently reported the impact of NPM1mut MRD burden and FLT3-ITD status on risk of relapse after allogeneic stem cell transplantation (Dillon, Blood 2020), however the clinical relevance of NPM1mut MP-LCN in patients who are not transplanted is unknown. We aimed to characterize the natural history of persistent NPM1mut MRD after chemotherapy and to identify factors associated with subsequent disease progression

Clinical impact of NPM1-mutant molecular persistence after chemotherapy for acute myeloid leukemia

Abstract Monitoring of NPM1 mutant (NPM1mut) measurable residual disease (MRD) in acute myeloid leukemia (AML) has an established role in patients who are treated with intensive chemotherapy. The European LeukemiaNet has defined molecular persistence at low copy number (MP-LCN) as an MRD transcript level <1% to 2% with a <1-log change between any 2 positive samples collected after the end of treatment (EOT). Because the clinical impact of MP-LCN is unknown, we sought to characterize outcomes in patients with persistent NPM1mut MRD after EOT and identify factors associated with disease progression. Consecutive patients with newly diagnosed NPM1mut AML who received ≥2 cycles of intensive chemotherapy were included if bone marrow was NPM1mut MRD positive at the EOT, and they were not transplanted in first complete remission. One hundred patients were followed for a median of 23.5 months; 42% remained free of progression at 1 year, either spontaneously achieving complete molecular remission (CRMRD−; 30%) or retaining a low-level NPM1mut transcript (12% for ≥12 months and 9% at last follow-up). Forty percent met the criteria for MP-LCN. Preemptive salvage therapy significantly prolonged relapse-free survival. Risk factors associated with disease progression were concurrent FLT3-internal tandem duplication at diagnosis and suboptimal MRD response (NPM1mut reduction <4.4-log) at EOT