GRP78 as a marker of pre-eclampsia: an exploratory study

Although the exact mechanisms that lead to shallow invasion or defective trophoblastic differentiation in pre-eclampsia are still unknown, it is widely admitted that the etiology of pre-eclampsia is a defect in trophoblast invasion of the uterine spiral arteries. We have previously observed that the status of a chaperone protein, glucose regulated protein 78 (GRP78) is associated with the invasive properties of cytotrophoblastic cells; we therefore hypothesized that circulating GRP78 could serve as a diagnostic tool in pre-eclampsia. In a prospective case-control study, we quantified GRP78 autoantibodies, complexes of GRP78 with autoantibodies and GRP78 (C-term fragment, N-term fragment and full-length GRP78) by ELISA. Plasma from women diagnosed with pre-eclampsia (n = 16), from women during the first trimester of pregnancy who subsequently developed pre-eclampsia (n = 10) and from healthy pregnant women (controls, n = 58 at term, n = 26 at first trimester) were analysed and compared. We observed no significant difference between pre-eclamptic and healthy pregnant women for autoantibodies-GRP78 complexes or total GRP78 at both first trimester and at delivery. In contrast, the ratio of C-terminal GRP78 over full length GRP78 was significantly different in plasma of pre-eclamptic patients as compared with controls both during first trimester (P < 0.004) and at term (P < 0.0001). Our findings suggest that circulating C-terminal GRP78 reflect the invasive properties of cells, and could be used as a predictive marker for pre-eclampsia early in pregnanc

Mesure des durées de vie des premiers niveaux excités du molybdène 93

Les durées de vie des six premiers niveaux excités du 93Mo ont été mesurées en utilisant l'effet Doppler associé à la réaction 93Nb(p, nγ)93Mo. Deux nouvelles durées de vie ont été obtenues et la précision des quatre autres a été améliorée

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

Squatina occulta, Hidden Angelshark

The Hidden Angelshark (Squatina occulta) is a medium-sized shark (to 160 cm total length) endemic to the Southwest Atlantic inhabiting waters from Rio de Janeiro, Brazil, to Buenos Aires Province, Argentina and likely further south to the northern Patagonia-Argentine region. It is mainly found on the continental shelf at depths of 10-150 m, but has been found at depths to 350 m. The species' low reproductive potential (litter size of 4-10 and a possible three-to-five-year female breeding cycle) together with its susceptibility to capture in both trawl and gillnet gear makes it highly susceptible to population depletion. Angel sharks are heavily fished in southern Brazil and significant reductions have been documented there. In the period from 1988 to 2002, on the continental shelf of southern Brazil, the abundance of Squatina species was reduced by approximately 85%, and benthic trawl fishing continued to intensively exploit this population in more recent years. In the same region, scientific fishing cruises conducted between 1986 to 2001 using bottom trawls revealed that the frequency of occurrence and CPUE (in kg/hour and number of individuals/hour) of this species was reduced by 80% confirming trends observed in commercial fisheries. In Argentina, trawl catches of Squatina underwent a reduction of 58% in the years 1992-1998, showing a continuing negative trend since then. These are the equivalent of a >99% reduction over three generation lengths (46.5 years), however there may be other areas within its range where fishing intensity is not as high. The catch and trade of this species has been banned in Brazil since 2004, but it is still targeted illegally and caught as bycatch and sold in markets. Given the species' relatively low productivity, the presence of intensive fisheries throughout the species' range, and the level of localized reductions reported, the Hidden Angelshark is inferred to have undergone a population reduction of over 80% over three generation lengths (46.5 years) across its range, and is therefore assessed as Critically Endangered A2bd.Fil: Awruch, C. A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; ArgentinaFil: Barreto, R.. Instituto Chico Mendes de Conservacao Da Biodiversidade; BrasilFil: 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: Faria, V.. Universidade Federal Do Ceara; BrasilFil: Paesch, L.. Dirección Nacional de Recursos Acuáticos; UruguayFil: Rincon, G.. Universidade Federal Do Maranhao.; Brasi

Recent Duplication and Functional Divergence in Parasitic Nematode Levamisole-Sensitive Acetylcholine Receptors

Helminth parasites rely on fast-synaptic transmission in their neuromusculature to experience the outside world and respond to it. Acetylcholine plays a pivotal role in this and its receptors are targeted by a wide variety of both natural and synthetic compounds used in human health and for the control of parasitic disease. The model, Caenorhabditis elegans is characterized by a large number of acetylcholine receptor subunit genes, a feature shared across the nematodes. This dynamic family is characterized by both gene duplication and loss between species. The pentameric levamisole-sensitive acetylcholine receptor has been characterized from C. elegans, comprised of five different subunits. More recently, cognate receptors have been reconstituted from multiple parasitic nematodes that are found to vary in subunit composition. In order to understand the implications of receptor composition change and the origins of potentially novel drug targets, we investigated a specific example of subunit duplication based on analysis of genome data for 25 species from the 50 helminth genome initiative. We found multiple independent duplications of the unc-29, acetylcholine receptor subunit, where codon substitution rate analysis identified positive, directional selection acting on amino acid positions associated with subunit assembly. Characterization of four gene copies from a model parasitic nematode, Haemonchus contortus, demonstrated that each copy has acquired unique functional characteristics based on phenotype rescue of transgenic C. elegans and electrophysiology of receptors reconstituted in Xenopus oocytes. We found evidence that a specific incompatibility has evolved for two subunits co-expressed in muscle. We demonstrated that functional divergence of acetylcholine receptors, driven by directional selection, can occur more rapidly than previously thought and may be mediated by alteration of receptor assembly. This phenomenon is common among the clade V parasitic nematodes and this work provides a foundation for understanding the broader context of changing anthelmintic drug targets across the parasitic nematodes

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

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

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

Pion radii in nonlocal chiral quark model

The electromagnetic radius of the charged pion and the transition radius of the neutral pion are calculated in the framework of the nonlocal chiral quark model. It is shown in this model that the contributions of vector mesons to the pion radii are noticeably suppressed in comparison with a similar contribution in the local Nambu--Jona-Lasinio model. The form-factor for the process gamma*pi+pi- is calculated for the -1 GeV^2<q^2<1.6 GeV^2. Our results are in satisfactory agreement with experimental data.Comment: 7 pages, 7 figure