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Enhanced biological phosphorus removal (EBPR) is an efficient and sustainable technology to remove phosphorus from wastewater. A widely known cause of EBPR deterioration in wastewater treatment plants (WWTPs) is the presence of nitrate/nitrite or oxygen in the anaerobic reactor. Moreover, most existing studies on the effect of either permanent aerobic conditions or inhibition of EBPR by nitrate or free nitrous acid (FNA) have been conducted with a Candidatus Accumulibacter or Tetrasphaera-enriched sludge, which are the two major reported groups of polyphosphate accumulating organisms (PAO) with key roles in full-scale EBPR WWTPs. This work reports the denitrification capabilities of a bio-P microbial community developed using glutamate as the sole source of carbon and nitrogen. This bio-P sludge exhibited a high denitrifying PAO (DPAO) activity, in fact, 56% of the phosphorus was uptaken under anoxic conditions. Furthermore, this mixed culture was able to use nitrite and nitrate as electron acceptor for P-uptake, being 1.8 mu g HNO2-N.L- 1 the maximum FNA concentration at which P-uptake can occur. Net P-removal was observed under permanent aerobic conditions. However, this microbial culture was more sensitive to FNA and permanent aerobic conditions compared to Ca. Accumulibacter-enriched sludge. ; Spanish Ministerio de Economia y CompetitividadSpanish Government [CTQ2014-60495-R, CTQ2017-82404-R]; Fondo Europeo de Desarrollo Regional (FEDER)European CommissionSpanish Government; Universitat Autonoma de Barcelona; GENOCOV research group (Grup de Recerca Consolidat de la Generalitat de Catalunya)Generalitat de Catalunya [2017SGR 1175] ; This work was supported by the Spanish Ministerio de Economia y Competitividad (CTQ2014-60495-R and CTQ2017-82404-R) with funds from the Fondo Europeo de Desarrollo Regional (FEDER). Natalia Rey is grateful for the PIF PhD grant funded by the Universitat Aut`onoma de Barcelona. The authors are members of the GENOCOV research group (Grup de Recerca Consolidat de la Generalitat de ...

Metabotropic glutamate receptors (mGluRs) are dimeric G-protein-coupled receptors activated by the main excitatory neurotransmitter, L-glutamate. mGluR activation by agonists binding in the venus flytrap domain is regulated by positive (PAM) or negative (NAM) allosteric modulators binding to the 7-transmembrane domain (7TM). We report the cryo-electron microscopy structures of fully inactive and intermediate-active conformations of mGlu5 receptor bound to an antagonist and a NAM or an agonist and a PAM, respectively, as well as the crystal structure of the 7TM bound to a photoswitchable NAM. The agonist induces a large movement between the subunits, bringing the 7TMs together and stabilizing a 7TM conformation structurally similar to the inactive state. Using functional approaches, we demonstrate that the PAM stabilizes a 7TM active conformation independent of the conformational changes induced by agonists, representing an alternative mode of mGlu activation. These findings provide a structural basis for different mGluR activation modes. ; We would like to thank Joël Bockaert, Chris Tate, Philippe Marin, and Richard Henderson for careful reading and for their comments on the manuscript. We would like to thank SLS PSI XA06 microfocus beamline scientist (Villigen; Switzerland), MRC Laboratory Molecular Biology EM and computing core facilities (Cambridge, UK), and the platform of pharmacology Arpeges of the Institut de Génomique Fonctionnelle (Montpellier, France). This project was funded by the ATIP grant from CNRS. C.N. was funded by the Post-doctoral program from Montpellier University. A.E.B. was supported by the Labex EpiGenMed (program "Investissements d'avenir," ANR-10-LABX-12-01), L.B. was supported by Ligue Contre le Cancer. J.F.-I., X.G.-S., J.C., and A.L. were supported by Ministerio de Ciencia e Innovación, Agencia Estatal de Investigación and ERDF-FEDER European Fund (project CTQ2017-89222-R) and by the Catalan government (2017 SGR 1604). J.-L.B. was supported by ANR (ANR-17-CE11-0011). J.-P.P. was supported by the Fondation Recherche Médicale (FRM team: DEQ20170326522), grants from ANR (DynaMuR2, ANR-18-CE11-0004; Lanthslider, ANR-17-CE11-0046). G.C. and K.R.V. were supported by Medical Research Council grant MC-U105184322. K.R.V. acknowledges SERB, India for the Ramanujan Fellowship (RJN-094/2017), DBT B-Life grant DBT/PR12422/MED/31/287/2014, and the support of the Department of Atomic Energy, Government of India, Government of India, under Project Identification No. RTI4006. G.L. was supported by ANR grants AT2R-TRAAK Bioanalgesics (ANR-17-CE18-0001), DynaMuR2 (ANR-18-CE11-0004), SWITCH-ON (ANR-20-CE11-0019), and Fondation Recherche Médicale (ING20121226326). ; Peer reviewed

We had characterized low-, medium- and high-molecular protein fractions of hepatocytes under development of glutamate-induced obesity and correction of nanocrystalline cerium dioxide and pioglitazone. Protein fractions were separated by electrophoresis using a 10 % Laemmli SDS-PAGE sodium dodecyl sulfate. Protein hepatocytes change under glutamate-induced obesity: high-protein reduced, and low-protein increased. Changes in hepatocyte proteins are consistent with previously established changes in protein content of hepatocytes under the influence HCD rich in fats and carbohydrates. We had noticed similar changes in protein of hepatocytes under correction cerium dioxide, but compared with glutamate-induced obesity, low proteins were lower. Pioglitazone didn't show a positive effect on hepatocyte proteins that may be associated with short-term administration.

Phenylazopyridines are photoisomerizable compounds with high potential to control biological functions with light. We have obtained a series of phenylazopyridines with light dependent activity as negative allosteric modulators (NAM) of metabotropic glutamate receptor subtype 5 (mGlu5). Here we describe the factors needed to achieve an operational molecular photoisomerization and its effective translation into in vitro and in vivo receptor photoswitching, which includes zebrafish larva motility and the regulation of the antinociceptive effects in mice. The combination of light and some specific phenylazopyridine ligands displays atypical pharmacological profiles, including light-dependent receptor overactivation, which can be observed both in vitro and in vivo. Remarkably, the localized administration of light and a photoswitchable compound in the peripheral tissues of rodents or in the brain amygdalae results in an illumination-dependent analgesic effect. The results reveal a robust translation of the phenylazopyridine photoisomerization to a precise photoregulation of biological activity. © 2016 American Chemical Society. ; We are grateful to C. Serra and L. Muñoz for synthetic and analytical support, F. Malhaire for technical support in cell-based pharmacological assays, and Y. Pérez for NMR support. This research has been supported by RecerCaixa foundation (2010ACUP00378 to P.G., J.G., and A.L.), the Marató de TV3 Foundation (110230 to J.G., 110231 to A.L., 110232 to C.G., and 111531 to P.G.), the Catalan government (2010 BP-A 00194 to X.R., 2012FI_B 01122 to S.P., 2012 CTP 00033 and 2012 BE1 00597 to X.G.-S., 2014SGR-1251 to P.G., and 2014SGR-00109 to A.L.), the Spanish Government (CTQ2014-57020-R and PCIN-2013-017-C03-01 to A.L., PIE14/00034, SAF2014-55700-P, and PCIN-2013-019-C03-03 to F.C., and SAF2014-58396-R to J.G.), AWT (SBO-140028) to F.C., and the ERANET Neuron LIGHTPAIN project (to A.L., F.C., J.G., and J.-P.P.); SynBio MODULIGHTOR, Human Brain Project WAVESCALES and Ramon Areces foundation grants (to P.G.); the Agence Nationale de la Recherche (ANR-16-CE16-0010 to A.L. and C.G.). ; Peer reviewed

<b><i>Aim:</i></b> The aim of this study was to evaluate the role of the glutamate receptor subunit-7 <i>(GluR7, GRIK 3)</i> rs6691840 (Ser310Ala, T928G) in the pathogenesis of alcohol dependence (AD). <b><i>Methods:</i></b> DNA was provided from AD patients (n = 209) and healthy control subjects (n = 308) all of Polish descent. The history of alcoholism was obtained using the Polish version of the SSAGA (Semi-Structured Assessment for the Genetics of Alcoholism). We conducted case-control association study and transmission disequilibrium test (TDT). <i>GRIK3 </i>functional polymorphism was genotyped by the PCR-RFLP method. <b><i>Results:</i></b> Analyses revealed that polymorphism Ser310Ala of <i>GRIK3</i> gene is not associated with AD or any of its subgroups. TDT reveled an adequate transmission of both alleles in the group of alcohol families. <b><i>Conclusions:</i></b> These findings replicate and extend our previous research results that do not support the hypothesis of the role of rs6691840 in the pathogenesis of AD.

The excitatory neurotransmitter glutamate has been reported to have a major impact on brain energy metabolism. Using primary cultures of rat hippocampal neurons, we observed that glutamate reduces glucose utilization in this cell type, suggesting alteration in mitochondrial oxidative metabolism. the aquaglyceroporin AQP9 and the monocarboxylate transporter MCT2, two transporters for oxidative energy substrates, appear to be present in mitochondria of these neurons. Moreover, they not only co-localize but they interact with each other as they were found to co-immunoprecipitate from hippocampal neuron homogenates. Exposure of cultured hippocampal neurons to glutamate 100 mu M for 1 h led to enhanced expression of both AQP9 and MCT2 at the protein level without any significant change at the mRNA level. in parallel, a similar increase in the protein expression of LDHA was evidenced without an effect on the mRNA level. These data suggest that glutamate exerts an influence on neuronal energy metabolism likely through a regulation of the expression of some key mitochondrial proteins. ; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) ; Swiss government scholarship ; Swiss National Foundation ; Universidade Federal de São Paulo, Dept Fisiol, São Paulo, Brazil ; Univ Lausanne, Dept Physiol, Lab Neuroenerget, Lausanne, Switzerland ; Universidade Federal de São Paulo, Dept Fisiol, São Paulo, Brazil ; FAPESP: 10/50349-1 ; Swiss government scholarship: 2011.0188 ; Swiss National Foundation: 31003A-125063 ; Swiss National Foundation: 31003A-140957 ; Web of Science