Antiplasmodial Activity of Nitroaromatic Compounds : Correlation with Their Reduction Potential and Inhibitory Action on Plasmodium falciparum Glutathione Reductase

With the aim to clarify the mechanism(s) of action of nitroaromatic compounds against the malaria parasite Plasmodium falciparum, we examined the single-electron reduction by P. falciparum ferredoxin:NADP+ oxidoreductase (PfFNR) of a series of nitrofurans and nitrobenzenes (n = 23), and their ability to inhibit P. falciparum glutathione reductase (PfGR). The reactivity of nitroaromatics in PfFNR-catalyzed reactions increased with their single-electron reduction midpoint potential (E17). Nitroaromatic compounds acted as non- or uncompetitive inhibitors towards PfGR with respect to NADPH and glutathione substrates. Using multiparameter regression analysis, we found that the in vitro activity of these compounds against P. falciparum strain FcB1 increased with their E17 values, octanol/water distribution coefficients at pH 7.0 (log D), and their activity as PfGR inhibitors. Our data demonstrate that both factors, the ease of reductive activation and the inhibition of PfGR, are important in the antiplasmodial in vitro activity of nitroaromatics. To the best of our knowledge, this is the first quantitative demonstration of this kind of relationship. No correlation between antiplasmodial activity and ability to inhibit human erythrocyte GR was detected in tested nitroaromatics. Our data suggest that the efficacy of prooxidant antiparasitic agents may be achieved through their combined action, namely inhibition of antioxidant NADPH:disulfide reductases, and the rapid reduction by single-electron transferring dehydrogenases-electrontransferases

Properties of projectile-fragments in the 40^{40}Ar + 27^{27}Al reaction at 44 A MeV. Comparison with a multisequential decay model

GANIL-EXPResults on projectile fragment–fragment coincidences in the forward direction and for the reaction 40Ar + 27Al at 44 A MeV are presented and compared with the predictions of two different entrance channel models, a two-body and a three-body mechanism both followed by a binary multisequential decay including fission. This analysis shows that many features of the projectile decay products are well accounted for by the binary multisequential decay model. However the results depend critically upon the initial masses and excitation energies of the primary projectile fragments. In this respect, the three-body approach underestimates the excitation energy imparted to the primary fragments whereas the two-body scenario overestimates it. The present data put strong constraints on the initial excitation energy imparted to the primary fragments which appears to be intermediate between the predictions of the two models

AntiMalarial Mode of Action (AMMA) Database: Data Selection, Verification and Chemical Space Analysis

© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim This paper presents the effort of collecting and curating a data set of 15461 molecules tested against the malaria parasite, with robust activity and mode of action annotations. The set is compiled from in-house experimental data and the public ChEMBL database subsets. We illustrate the usefulness of the dataset by building QSAR models for antimalarial activity and QSPR models for modes of actions, as well as by the analysis of the chemical space with the Generative Topographic Mapping method. The GTM models perform well in prediction of both activity and mode of actions, on par with the classical SVM methods. The visualization of obtained maps helps to understand the distribution of molecules corresponding to different modes of action: molecules with similar targets are located close to each other on the map. Therefore, this analysis may suggest new modes of action for non-annotated or even annotated compounds. In perspective, this can be used as a tool for prediction of both antimalarial activity and target for novel, untested compounds

Dynamical effects in multifragmentation at intermediate energies

The fragmentation of the quasi-projectile is studied with the INDRA multidetector for different colliding systems and incident energies in the Fermi energy range. Different experimental observations show that a large part of the fragmentation is not compatible with the statistical fragmentation of a fully equilibrated nucleus. The study of internal correlations is a powerful tool, especially to evidence entrance channel effects. These effects have to be included in the theoretical descriptions of nuclear multifragmentation.Comment: 13 pages, 26 figures, submitted to Physical Review

Transition from participant to spectator fragmentation in Au+Au reaction between 60 AMeV and 150 AMeV

Using the quantum molecular dynamics approach, we analyze the results of the recent INDRA Au+Au experiments at GSI in the energy range between 60 AMeV and 150 AMeV. It turns out that in this energy region the transition toward a participant-spectator scenario takes place. The large Au+Au system displays in the simulations as in the experiment simultaneously dynamical and statistical behavior which we analyze in detail: The composition of fragments close to midrapidity follows statistical laws and the system shows bi-modality, i.e. a sudden transition between different fragmentation pattern as a function of the centrality as expected for a phase transition. The fragment spectra at small and large rapidities, on the other hand, are determined by dynamics and the system as a whole does not come to equilibrium, an observation which is confirmed by FOPI experiments for the same system.Comment: published versio

Bathyraja multispinis, Multispine Skate

The Multispine Skate (Bathyraja multispinis) is a medium-sized (to 126 cm total length) skate that occurs in the Southeast Pacific Ocean from Coquimbo, Chile to Cape Horn and in the Southwest Atlantic Ocean from Santa Catarina, Brazil to Tierra del Fuego and the Falkland Islands (Malvinas) and is demersal on the continental and insular shelves and slopes at depths of 70-740 m. It is captured in demersal trawl and longline fisheries that operate throughout its range and there is little refuge at depth; it is likely to be retained for sale for human consumption in the Southwest Atlantic, but is discarded dead in the Southeast Pacific. Across its range, skates are typically not recorded or managed at the species level, and there are no estimates of population size. In Argentina, there are no species-specific data, but rays in general declined in catch-per-unit-effort (CPUE) in the 1990s and early 2000s. In the Falkland Islands (Malvinas) target skate fishery, this species showed an either stable or increasing trend in CPUE over the time-series from 1994 to 2013. Overall, due to the level of inadequately managed fisheries it is exposed to, general declines of skates in some parts of its range, and its lack of refuge at depth, balanced with the increase in CPUE in the Falkland Islands (Malvinas), it is suspected that this skate has undergone a population reduction of 20-29% over the past three generations (45 years). Therefore, the Multispine Skate is assessed as Near Threatened, nearly meeting the threshold for Vulnerable A2bd.Fil: Pollom, R.. University Fraser Simon; CanadáFil: Dulvy, N. K.. University Fraser Simon; CanadáFil: Acuña, E.. Universidad Católica del Norte; ChileFil: Bustamante, C.. Universidad de Antofagasta; ChileFil: Charvet, P.. Universidade Federal do Paraná; BrasilFil: Chiaramonte, Gustavo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia". Estación Hidrobiológica de Puerto Quequén (sede Quequén); ArgentinaFil: Cuevas, J. M.. Wildlife Conservation Society; Estados UnidosFil: Herman, K.. Georgia Aquarium; Estados UnidosFil: Paesch, L.. Dirección Nacional de Recursos Acuáticos; UruguayFil: Pompert, J.. No especifíca;Fil: Velez Zuazo, X.. Smithsonian Conservation Biology Institute; Estados Unido

Bathyraja brachyurops, Broadnose Skate

The Broadnose Skate (Bathyraja brachyurops) is a medium-sized (to 125 cm total length) skate that occurs in the Southeast Pacific and Southwest Atlantic Oceans from Biobío, Chile, south around Cape Horn and north to Rio Grande do Sul, Brazil, including the Falkland Islands (Malvinas). It is demersal on the inner continental shelf and upper slope at depths of 28?604 m. This skate is taken as bycatch in inadequately-managed demersal trawl and longline fisheries throughout most of its range. In the Argentina-Uruguay Common Fishing Zone, it is taken as bycatch but recorded with all other coastal skates. Species-specific catch time-series for Argentinian fisheries are unavailable, but overall skate landings were minimal prior to 1994 before rising rapidly and reaching a peak in 2007 and then dropping again until 2017. It is one of the main species captured in the Falkland Islands (Malvinas) multispecies target skate fishery, where the catch-per-unit-effort time-series suggests its relative abundance increased over the period 1994?2013. In Chile, it is a retained bycatch of the commercial longline fishery targeting Yellownose Skate, and in trawl fisheries targeting Chilean Hake and crustaceans. Overall, due to the level of fishing pressure that this skate is exposed to throughout much of its geographic range, its limited refuge at depth, its continued common presence in fisheries catches, and its moderately productive life history that allows it to withstand some fishing pressure, combined with an increasing trend in the Falkland Islands (Malvinas) and declines in skates in general elsewhere in its range, it is suspected that a population reduction of 20-29% has occurred over the past three generations (42 years). Therefore, the Broadnose Skate is assessed as Near Threatened, nearly meeting the threshold under criterion A2bd.Fil: Pollom, R.. University Fraser Simon; CanadáFil: Dulvy, N. K.. University Fraser Simon; CanadáFil: Acuña, E.. Universidad Católica del Norte; ChileFil: Bustamante, C.. Universidad de Antofagasta; ChileFil: Charvet, P.. Universidade Federal do Paraná; BrasilFil: Chiaramonte, Gustavo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia". Estación Hidrobiológica de Puerto Quequén (sede Quequén); ArgentinaFil: Cuevas, J. M.. Wildlife Conservation Society; Estados UnidosFil: Herman, K.. Georgia Aquarium; Estados UnidosFil: Paesch, L.. Dirección Nacional de Recursos Acuáticos; UruguayFil: Pompert, J.. No especifíca;Fil: Velez Zuazo, X.. No especifíca

Multifragmentation process for different mass asymmetry in the entrance channel around the Fermi energy

The influence of the entrance channel asymmetry upon the fragmentation process is addressed by studying heavy-ion induced reactions around the Fermi energy. The data have been recorded with the INDRA 4pi array. An event selection method called the Principal Component Analysis is presented and discussed. It is applied for the selection of central events and furthermore to multifragmentation of single source events. The selected subsets of data are compared to the Statistical Multifragmentation Model (SMM) to check the equilibrium hypothesis and get the source characteristics. Experimental comparisons show the evidence of a decoupling between thermal and compresional (radial flow) degrees of freedom in such nuclear systems.Comment: 28 pages, 15 figures, article sumitted to Nuclear Physics

Response of CsI(Tl) scintillators over a large range in energy and atomic number of ions (Part I): recombination and delta -- electrons

A simple formalism describing the light response of CsI(Tl) to heavy ions, which quantifies the luminescence and the quenching in terms of the competition between radiative transitions following the carrier trapping at the Tl activator sites and the electron-hole recombination, is proposed. The effect of the delta rays on the scintillation efficiency is for the first time quantitatively included in a fully consistent way. The light output expression depends on four parameters determined by a procedure of global fit to experimental data.Comment: 28 pages, 6 figures, submitted to Nucl. Inst. Meth.