Evaluating 5-nitrothiazoles as trypanocidal agents

OA Monitor ExerciseOA Monitor ExerciseThe growth inhibitory properties of a 5-nitrothiazole series was evaluated against Trypanosoma brucei. A subset of related compounds displayed the greatest potency towards the parasite while exhibiting little cytotoxic effect on mammalian cells, with this anti-parasitic activity being dependent on expression of a type I nitroreductase by the trypanosome. We conclude that the 5-nitrothiazole class of nitroheterocycle may represent new leads in the treatment of human African trypanosomiasis.BAV acknowledges financial support by FONDECYT Postdoctorado 313036

3-Nitrotriazole-based piperazides as potent antitrypanosomal agents

publisher: Elsevier articletitle: 3-Nitrotriazole-based piperazides as potent antitrypanosomal agents journaltitle: European Journal of Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.ejmech.2015.08.042 content_type: article copyright: Copyright © 2015 Elsevier Masson SAS. All rights reserved.publisher: Elsevier articletitle: 3-Nitrotriazole-based piperazides as potent antitrypanosomal agents journaltitle: European Journal of Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.ejmech.2015.08.042 content_type: article copyright: Copyright © 2015 Elsevier Masson SAS. All rights reserved.publisher: Elsevier articletitle: 3-Nitrotriazole-based piperazides as potent antitrypanosomal agents journaltitle: European Journal of Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.ejmech.2015.08.042 content_type: article copyright: Copyright © 2015 Elsevier Masson SAS. All rights reserved.publisher: Elsevier articletitle: 3-Nitrotriazole-based piperazides as potent antitrypanosomal agents journaltitle: European Journal of Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.ejmech.2015.08.042 content_type: article copyright: Copyright © 2015 Elsevier Masson SAS. All rights reserved

Discovery of potent nitrotriazole-based antitrypanosomal agents: In vitro and in vivo evaluation

publisher: Elsevier articletitle: Discovery of potent nitrotriazole-based antitrypanosomal agents: In vitro and in vivo evaluation journaltitle: Bioorganic & Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.bmc.2015.08.014 content_type: article copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.publisher: Elsevier articletitle: Discovery of potent nitrotriazole-based antitrypanosomal agents: In vitro and in vivo evaluation journaltitle: Bioorganic & Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.bmc.2015.08.014 content_type: article copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.publisher: Elsevier articletitle: Discovery of potent nitrotriazole-based antitrypanosomal agents: In vitro and in vivo evaluation journaltitle: Bioorganic & Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.bmc.2015.08.014 content_type: article copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.publisher: Elsevier articletitle: Discovery of potent nitrotriazole-based antitrypanosomal agents: In vitro and in vivo evaluation journaltitle: Bioorganic & Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.bmc.2015.08.014 content_type: article copyright: Copyright © 2015 Elsevier Ltd. All rights reserved

Tracking Holocene palaeostratification and productivity changes in the Western Irish Sea: A multi-proxy record

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.The Western Irish Sea preserves an exceptionally thick (ca. 40 m) Holocene succession that is ideally suited to understanding the pattern of palaeostratification and water mass productivity changes in the region, and their relationship with sea level, sedimentation, and biota. Additionally, the presence of shallow-buried methane provides an opportunity to explore its potential impact on the local pattern of Holocene marine environmental change. Multi-proxy investigation of a cored borehole succession through the Holocene interval tracks changes from mixed to seasonally stratified conditions. In the earliest Holocene (11.2–10 ka), high productivity, mixed water conditions prevailed, with abundant and diverse foraminifera and dominant heterotrophic dinoflagellate cysts. Productivity was probably driven by high nutrient fluxes related to high rates of sedimentation (>1600 cm/kyr), in turn influenced by relatively low sea level and restricted sediment accommodation space across shelf areas to the east of the borehole site (eastern Irish Sea Basin). With rising sea level in the later part of the Early Holocene, the region evolved into a relatively lower productivity mixed water mass system, with significant changes in ecology revealed by dinoflagellate cysts and foraminifera. In the latest Early Holocene and earliest Mid Holocene (ca. 8.4–8.2 ka) a return to higher productivity is signalled by dinoflagellate cyst data; a result of seasonal stratification becoming established, evidenced by sharply increased summer sea surface temperature estimates (typically 16–17 °C) that contrast with an opposite (more positive) trend in δ18O values for benthic foraminifera. Reductions in turbulent mixing associated with stratification might have exacerbated the palaeoecological impact of shallow-buried methane associated with the borehole site, potentially evidenced by a significant change in dominant benthic foraminifera and strong, localised excursions in the benthic δ13C/δ18O record

Intra-Genomic Ribosomal RNA Polymorphism and Morphological Variation in Elphidium macellum Suggests Inter-Specific Hybridization in Foraminifera

Elphidium macellum is a benthic foraminifer commonly found in the Patagonian fjords. To test whether its highly variable morphotypes are ecophenotypes or different genotypes, we analysed 70 sequences of the SSU rRNA gene from 25 specimens. Unexpectedly, we identified 11 distinct ribotypes, with up to 5 ribotypes co-occurring within the same specimen. The ribotypes differ by varying blocks of sequence located at the end of stem-loop motifs in the three expansion segments specific to foraminifera. These changes, distinct from typical SNPs and indels, directly affect the structure of the expansion segments. Their mosaic distribution suggests that ribotypes originated by recombination of two or more clusters of ribosomal genes. We propose that this expansion segment polymorphism (ESP) could originate from hybridization of morphologically different populations of Patagonian Elphidium. We speculate that the complex geological history of Patagonia enhanced divergence of coastal foraminiferal species and contributed to increasing genetic and morphological variation

Determination of the Strong Phase in D0 -> K+pi- Using Quantum-Correlated Measurements

We exploit the quantum coherence between pair-produced D0 and D0bar in psi(3770) decays to study charm mixing, which is characterized by the parameters x and y, and to make a first determination of the relative strong phase \delta between D0 -> K+pi- and D0bar -> K+pi-. Using 281 pb^-1 of e^+e^- collision data collected with the CLEO-c detector at E_cm = 3.77 GeV, as well as branching fraction input and time-integrated measurements of R_M = (x^2+y^2)/2 and R_{WS} = Gamma(D0 -> K+pi-)/Gamma(D0bar -> K+pi-) from other experiments, we find \cos\delta = 1.03 +0.31-0.17 +- 0.06, where the uncertainties are statistical and systematic, respectively. By further including other mixing parameter measurements, we obtain an alternate measurement of \cos\delta = 1.10 +- 0.35 +- 0.07, as well as x\sin\delta = (4.4 +2.7-1.8 +- 2.9) x 10^-3 and \delta = 22 +11-12 +9-11 degrees.Comment: 5 pages, also available through http://www.lns.cornell.edu/public/CLNS/2007/. Incorporated referees' comment