Assessment of co–contaminant effects on uranium and thorium speciation in freshwater using geochemical modelling

Speciation modelling of uranium (as uranyl) and thorium, in four freshwaters impacted by mining activities, was used to evaluate (i) the influence of the co–contaminants present on the predicted speciation, and (ii) the influence of using nine different model/database combinations on the predictions. Generally, co–contaminants were found to have no significant effects on speciation, with the exception of Fe(III) in one system, where formation of hydrous ferric oxide and adsorption of uranyl to its surface impacted the predicted speciation. Model and database choice on the other hand clearly influenced speciation prediction. Complexes with dissolved organic matter, which could be simulated by three of the nine model/database combinations, were predicted to be important in a slightly acidic, soft water. Model prediction of uranyl and thorium speciation needs to take account of database comprehensiveness and cohesiveness, including the capability of the model and database to simulate interactions with dissolved organic matter. Measurement of speciation in natural waters is needed to provide data that may be used to assess and improve model capabilities and to better constrain the type of predictive modelling work presented here

Mitochondrion targeted trypanosome alternative oxidase inhibitors as chemotherapeutic agents against T. brucei

Trabajo presentado en el XII SEQT Mini Symposium. IIIrd Spanish/Portuguese/Brazilian Meeting, celebrado en Madrid del 17 al 18 de noviembre de 2016.During their life-cycle, trypanosomes adapt their energy metabolism to the availability of nutrients in their environment. Hence, procyclic forms of T. brucei have a fully functional respiratory chain and synthesize ATP by oxidative phosphorylation in the mitochondrion. In contrast, respiration of bloodstream forms (BSF) of T. brucei (i.e. the human-infective form) relies exclusively on glycolysis for energy production. The trypanosome alternative oxidase (TAO) is the sole terminal oxidase enzyme to re-oxidize NADH accumulated during glycolysis. It is a cyanide-resistant and cytochrome-independent ubiquinol oxidase which is sensitive to the specific inhibitors salicylhydroxamic acid (SHAM) and ascofuranone. This enzyme which is essential to the viability of BSF trypanosomes and has no counterpart in the mammalian host is a potential target for chemotherapy. To boost the activity of TAO inhibitors against T. brucei, we investigated a chemical strategy consisting in the conjugation of the inhibitor with lipophilic cations (LC) that can cross lipid bilayers by non-carrier mediated transport, and thus accumulate specifically into the mitochondrion, driven by the plasma and mitochondrial transmembrane potentials (negative inside). This design afforded several LC¿TAO inhibitor conjugates active in the submicromolar to low nanomolar range against wild type and resistant strains of African trypanosomes (T. b. brucei, T. congolense). Selectivity over human cells was >500. Studies of the effects on purified TAO, parasite respiration, mitochondrial membrane potential (¿m), and cell cycle suggest that TAO is a likely target of the compounds in vivo

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe

Determining redox properties of clay-rich sedimentary deposits in the context of performance assessment of radioactive waste repositories : Conceptual and practical aspects

Redox reactions play a key factor controlling the mobility of redox sensitive radionuclides in clay-rich sediments which might serve as host formations for radioactive waste repositories. Assessing the redox speciation of radionuclides requires information about the redox conditions in the formation and the electron transfer kinetics between the redox active constituents in the sediment and the radionuclides. Clay-rich sediments, like most natural systems, are usually not in redox-equilibrium when they received sufficient organic material during deposition to enforce anaerobic conditions during early diagenesis. Consequently, any derived redox potential (Eh) to characterize the conditions in the formation should include an evaluation about which half reactions were probed by the used technique or indicate for which half reaction(s) the value was calculated. Conventional Eh measurements, performed with an inert electrode in the pore water retrieved from clay-rich sediments, are unlikely to provide meaningful values. This is due to the intrinsic limitations of this technique to probe the redox potential of environmentally relevant dissolved constituents and because many redox reactions in clay-rich sediments involve solids. Electrochemical techniques which probe the redox properties of solids in aqueous suspensions or in salt matrix are promising alternatives but their applicability in clay-rich sediments still has to be tested. When these techniques live up to the expectations, their application in combination with geochemical characterization and thermodynamic calculations might be the most reliable approach to constrain the Eh of redox active constituents in clay-rich sediments. A large variety of redox active species of the elements H, O, N, C, Fe, Mn and S might be present in clay-rich sediments. A straightforward approach to obtain Eh values for various redox couples in the sediment is to use thermodynamic calculations in combination with a rigorous geochemical characterization of the sediment. However, not for all redox active species, which are of possible importance for controlling the redox states of radionuclides, reliable thermodynamic data are available. This is in particular the case for structurally bound Fe in clay minerals, organic matter, and secondary minerals formed during early diagenesis or after burial. The role of many of these redox couples for redox transformations of radionuclides has been experimentally investigated under environmentally relevant conditions. Examples for different reactions are compiled in this report. In general, the reduction of oxidized species of U, Se, and Tc by reduced species of Fe, S, and C in the absence or presence of microbial mediation have been frequently studied. Studies on transuranium elements, other redox sensitive radionuclides, and the oxidation of radionuclides are more rare. Information about the kinetics of redox reactions between radionuclides and the oxidized or reduced species of redox sensitive major elements in the formation should be used to interpret the Eh value(s) obtained for one or more redox couples in the formation. An Eh value obtained for a redox couple in the sediment is only of relevance for predicting the redox state of a radionuclide when the time scale of the redox reaction is shorter than the half-life of the radionuclide and the residence time of the radionuclide in the formation. Often, redox reactions between radionuclides and redox active constituents of the clay-rich sediment only proceed rapidly in one direction while the reaction in opposite direction is kinetically hindered. In this case, the Eh derived for a redox couple in the sediment should only be used as an upper or lower limit to constrain the redox speciation of the radionuclide of interest. As a general conclusion, it can be stated that while clay-rich sediments in many cases are considered to be reducing, the exact redox potential, the in situ activity of the various redox couples, and their effect on redox sensitive radionuclides are less evident. This frequently results in pragmatic and stylised approaches when transferring phenomenological knowledge to safety assessment calculations

Non-thermal plasmas in and in contact with liquids

During the last two decades atmospheric ( or high) pressure non-thermal plasmas in and in contact with liquids have received a lot of attention in view of their considerable environmental and medical applications. The simultaneous generation of intense UV radiation, shock waves and active radicals makes these discharges particularly suitable for decontamination, sterilization and purification purposes. This paper reviews the current status of research on atmospheric pressure non-thermal discharges in and in contact with liquids. The emphasis is on their generation mechanisms and their physical characteristics