2013 REU Poster: Purification and Characterization of a Ferredoxin from Mycobacterium tuberculosis

Poster presentation at REU Summer's End Research Symposium, 2013, by REU participant Jonas A, de Oliveira, MassBay Community College - Sean Elliott group, Evan Judd lab mentorM. tuberculosis possesses a sulfite reductase (MtsirA) that is over-expressed when the bacteria is in its dormant stage of infection. MtSirA catalyzes the six-electron reduction of sulfite to sulfide. Previous kinetic studies of MtsirA have used methyl viologen (MV), a chemical reductant, as an electron donor. The goal of this work is to purify and characterize a ferredoxin from M. tuberculosis (MtFd) and determine if MtFd can act as an electron donor to mtSirA, with the ultimate goal of using it as a more physiologically relevant electron donor in kinetic studies of mtSirA. We have found that that MtFd purifies without a cluster and must be chemically reconstituted. MtFd likely contains a [4Fe-4S] cluster, and may be able to donate electrons to mtSirA.NSF-RE

Enasidenib in the treatment of relapsed/refractory acute myeloid leukemia: an evidence-based review of its place in therapy.

Introduction: Acute myeloid leukemia (AML) remains a disease with high mortality, especially for older patients and those with relapsed/refractory (R/R) disease. With recent advances in molecular testing, targeting particular leukemogenic mutations such as those occurring in isocitrate dehydrogenase (IDH) became possible. Enasidenib is a new small-molecule inhibitor of mutant isocitrate dehydrogenase-2 (IDH2). Aim: The objective of this article is to review the evidence for the use of enasidenib in R/R AML, as well as to outline future directions of enasidenib therapy. Evidence Review: Enasidenib was approved in August 2017, after a successful Phase I/II trial showing an overall response rate (ORR) of 40.3% in R/R disease, with 19.3% of patients achieving complete remission (CR). Enrollees in the trial were mostly older adults. The most prominent toxicities were hyperbilirubinemia and IDH-differentiation syndrome (IDH-DS), though the drug was generally well tolerated and the maximum tolerated dose was not reached. A Phase III trial is currently ongoing. Conclusion: Enasidenib provides a new therapeutic option for patients with R/R AML. Further studies are ongoing to ascertain its role in combination with other agents and newly diagnosed disease

Hipsters on Networks: How a Small Group of Individuals Can Lead to an Anti-Establishment Majority

The spread of opinions, memes, diseases, and "alternative facts" in a population depends both on the details of the spreading process and on the structure of the social and communication networks on which they spread. In this paper, we explore how \textit{anti-establishment} nodes (e.g., \textit{hipsters}) influence the spreading dynamics of two competing products. We consider a model in which spreading follows a deterministic rule for updating node states (which describe which product has been adopted) in which an adjustable fraction $p_{\rm Hip}$ of the nodes in a network are hipsters, who choose to adopt the product that they believe is the less popular of the two. The remaining nodes are conformists, who choose which product to adopt by considering which products their immediate neighbors have adopted. We simulate our model on both synthetic and real networks, and we show that the hipsters have a major effect on the final fraction of people who adopt each product: even when only one of the two products exists at the beginning of the simulations, a very small fraction of hipsters in a network can still cause the other product to eventually become the more popular one. To account for this behavior, we construct an approximation for the steady-state adoption fraction on $k$-regular trees in the limit of few hipsters. Additionally, our simulations demonstrate that a time delay $\tau$ in the knowledge of the product distribution in a population, as compared to immediate knowledge of product adoption among nearest neighbors, can have a large effect on the final distribution of product adoptions. Our simple model and analysis may help shed light on the road to success for anti-establishment choices in elections, as such success can arise rather generically in our model from a small number of anti-establishment individuals and ordinary processes of social influence on normal individuals.Comment: Extensively revised, with much new analysis and numerics The abstract on arXiv is a shortened version of the full abstract because of space limit

Group VIII Coordination Chemistry of a Pincer-Type Bis(8-quinolinyl)amido Ligand

This paper provides an entry point to the coordination chemistry of the group VIII chemistry of the bis(8-quinolinyl)amine (BQA) ligand. In this context, mono- and disubstituted BQA complexes of iron, ruthenium, and osmium are described. For example, the low-spin bis-ligated Fe(III) complex [Fe(BQA)2][BPh4] has been prepared via amine addition to FeCl3 in the presence of a base and NaBPh4. Complexes featuring a single BQA ligand are more readily prepared for Ru and Os. Auxiliary ligands featuring a single BQA ligand, along with two other L-type donor ligands, allow for a variety of ligand types to occupy a sixth coordination site. Representative examples include the halide and pseudohalide complexes trans-(BQA)MX(PPh3)2 (M = Ru, Os; X = Cl, Br, N3, OTf), as well as the hydride and alkyl complexes trans-(BQA)RuH(PMe3)2 and trans-(BQA)RuMe(PMe3)2. Electrochemical studies are discussed that help to contextualize the BQA ligand with respect to its neutral counterpart 2,2′,2′′-terpyridine (terpy) in terms of electron-releasing character. Bidentate ligands have been explored in conjunction with the BQA ligand. Thus, the bidentate, monoanionic aryl(8-quinolinyl)amido ligand 3,5-(CF3)2-(C6H3)QA has been installed onto the (BQA)Ru platform to provide (BQA)Ru(3,5-(CF3)2-(C6H3)QA)(PPh3). A bis(phosphino)borate ligand stabilizes the five-coordinate complex [Ph2B(CH2PPh2)2]Ru(BQA). Finally, access to dinitrogen complexes of the types [(BQA)Ru(N2)(PPh3)2][PF6], [(BQA)Ru(N2)(PMe3)2][PF6], and [(BQA)Os(N2)(PPh3)2][PF6] is provided by exposure of the sixth coordination site under a N2 atmosphere