103 research outputs found

    Genetic polymorphisms located in TGFB1, AGTR1, and VEGFA genes are associated to chronic renal allograft dysfunction

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    Background: Persistent inflammation and fibrosis have been related to active progression of renal deterioration and reduced survival of kidney transplant. The aim of this study was to determine the impact of single-nucleotide polymorphisms (SNPs) located in regions related to inflammatory and immune processes on the development of chronic renal allograft dysfunction (CRAD). Methods: A retrospective study was carried out on 276 patients who received kidney transplant (KT). SNPs were genotyped via the SNPlex platform. Statistical analysis was performed with SNPstat and regression logistic analyses were adjusted by age and gender of recipients and donors, cold ischemia time and the number of human leukocyte antigen (HLA) mismatches. Results: From 276 patients with KT, 118 were non-CRAD and 158 were CRAD. Three SNPs showed significant associations with CRAD development: rs1800471 in transforming growth factor beta 1 (TGFB1), rs5186 in angiotensin II receptor type 1 (AGTR1), and rs699947 in vascular endothelial growth factor A (VEGFA). GC genotype of rs1800471 was associated with increased odds of CRAD compared to GG genotype (OR=2.65 (95% confidence interval (CI)=1.09; 6.47), p=0.025), as well as AC and AA genotype of rs699947 assuming a dominant model (OR=1.80 (95% CI=1.02; 3.20), p=0.044). Besides, AC and CC genotypes of rs5186 were associated with reduced odds of CRAD assuming a dominant model (OR=0.56 (95% CI=0.33; 0.96), p=0.033). Conclusion: Our findings suggest that three genes related to immunity and inflammation (rs1800471, rs5186 and rs699947) are associated to susceptibility or protection to CRAD, and might have diagnostic utility in predicting the likelihood of developing CRAD.This work was supported by two Grants from Instituto de Salud Carlos III (Ref: PI08/0738 and PI11/00245) and from Junta de Castilla y León (Ref: GRS 234/A/08). MAJs, AFR and MGF are supported by Grants from Instituto de Salud Carlos III, CM10/00105, UIPY-1377/08 and CM09/00031, respectively.S

    Evidence of the participation of electronic excited states in the mechanism of positronium formation in substitutional Tb1-xEux(dpm)(3) solid solutions studied by optical and positron annihilation spectroscopies

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    Positronium formation in the bimary molecular solid solutions Tb1-xEux (dpm)(3) (dpm = dipivaloylmethanate) has been investigated. A strong linear correlation between the D-5(4) Tb(III) energy level excited state lifetime and the positronium formation probability has been observed. This correlation indicates that the ligand-to-metal charge transfer LMCT states act in both luminescence quenching and positronium formation inhibition, as previously proposed. A kinetic mechanism is proposed to explain this correlation and shows that excited electronic states have a very important role in the positronium formation mechanism.CNPqCNPqFAPEMIGFAPEMIGFAPESPFAPESPRENAMI (National Project)RENAMI (National Project

    Levels and spatial distribution of organochlorinated compounds and polycyclic aromatic hydrocarbons in fishes from a Mediterranean coastal lagoon

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    The seasonal input and distribution of organic contaminants in the Mar Menor lagoon have been recently characterized in seawater and sediments, showing the significant impact of flash flood events. Mar Menor is a hypersaline (42-47 psu) coastal lagoon located in the Cartagena Field area at the South East of Spain subjected mainly to intensive agriculture, seasonal tourism and recreational activities. The bioaccumulation of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and organochlorinated pesticides (OCPs) has been also determined in bivalves, but no information was available about their accumulation in fishes. In this study the concentrations of PAHs, PCBs and OCPs in golden grey mullet (Liza aurata) and red mullet (Mullus barbatus) muscle were determined. Their spatial distribution throughout the Mar Menor lagoon was characterized considering 9 sampling areas and two different sampling periods, spring and autumn in 2010 for golden grey mullet and only one (autumn) for red mullet. PAHs and organochlorinated pollutants were extracted using specific Soxhlet procedures. After cleanup and purification steps the final extracts were analyzed by HPLC for PAHs, and by GC-MS for PCBs and OCPs. The higher concentrations of all pollutants were found close to main urban and port areas of this lagoon and in the influence area of El Albujón watercourse. PAHs concentrations (sum of 14 congeners) in both species varied between 1 and 20.7 g/kg w.w. being pyrene and phenanthrene the most abundant ones. p,p’DDE showed higher concentrations than PAHs in golden grey mullet (concentration range: 0.2-32.7 g/kg w.w.), specially close to the main navigation channel between this lagoon and the Mediterranean Sea.This work has been supported by the Spanish Inter-Ministerial Science and Technology Commission through ‘DECOMAR’ project (CICYT, CTM2008-01832) and by Seneca Foundation (Region of Murcia, Spain) through ‘BIOMARO’ project (15398/PI/10). Rubén Moreno-González wishes to thank the Spanish Ministry of Science and Innovation for the FPI grant (BES 2009-014713)

    Dopaminergic control of ADAMTS2 expression through cAMP/CREB and ERK: molecular effects of antipsychotics

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    © The Author(s) 2019.A better understanding of the molecular mechanisms that participate in the development and clinical manifestations of schizophrenia can lead to improve our ability to diagnose and treat this disease. Previous data strongly associated the levels of deregulated ADAMTS2 expression in peripheral blood mononuclear cells (PBMCs) from patients at first episode of psychosis (up) as well as in clinical responders to treatment with antipsychotic drugs (down). In this current work, we performed an independent validation of such data and studied the mechanisms implicated in the control of ADAMTS2 gene expression. Using a new cohort of drug-naïve schizophrenia patients with clinical follow-up, we confirmed that the expression of ADAMTS2 was highly upregulated in PBMCs at the onset (drug-naïve patients) and downregulated, in clinical responders, after treatment with antipsychotics. Mechanistically, ADAMTS2 expression was activated by dopaminergic signalling (D1-class receptors) and downstream by cAMP/CREB and mitogen-activated protein kinase (MAPK)/ERK signalling. Incubation with antipsychotic drugs and selective PKA and MEK inhibitors abrogated D1-mediated activation of ADAMTS2 in neuronal-like cells. Thus, D1 receptors signalling towards CREB activation might participate in the onset and clinical responses to therapy in schizophrenia patients, by controlling ADAMTS2 expression and activity. The unbiased investigation of molecular mechanisms triggered by antipsychotic drugs may provide a new landscape of novel targets potentially associated with clinical efficacy.This work was supported by: SAF2016-76046-R and SAF2013-46292-R (MINECO and FEDER) to B.C.F., PI16/00156 (isciii and FEDER) to J.P.V., LUCHAMOS POR LA VIDA project to F.R.J. and J.P.V., SAF2017-83702-R (MINECO and FEDER), Red TERCEL RD12/0019/0024 (ISCIII) and GVA-PROMETEO 2018/041 (Generalitat Valenciana) to S.M. J.P.V. is supported by the RyC research programme (RYC-2013-14097) and F.R.J. by the predoctoral research programme (BES-2014-070615), from MINECO and FEDER

    On the functional use of the membrane compartmentalized pool of ATP by the Na+ and Ca++ pumps in human red blood cell ghosts

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    Previous evidence established that a sequestered form of adenosine triphosphate (ATP pools) resides in the membrane/cytoskeletal complex of red cell porous ghosts. Here, we further characterize the roles these ATP pools can perform in the operation of the membrane's Na+ and Ca2+ pumps. The formation of the Na+- and Ca2+-dependent phosphointermediates of both types of pumps (ENa-P and ECa-P) that conventionally can be labeled with trace amounts of [γ-3P]ATP cannot occur when the pools contain unlabeled ATP, presumably because of dilution of the [γ-3P]ATP in the pool. Running the pumps forward with either Na+ or Ca2+ removes pool ATP and allows the normal formation of labeled ENa-P or ECa-P, indicating that both types of pumps can share the same pools of ATP. We also show that the halftime for loading the pools with bulk ATP is 10–15 minutes. We observed that when unlabeled “caged ATP” is entrapped in the membrane pools, it is inactive until nascent ATP is photoreleased, thereby blocking the labeled formation of ENa-P. We also demonstrate that ATP generated by the membrane-bound pyruvate kinase fills the membrane pools. Other results show that pool ATP alone, like bulk ATP, can promote the binding of ouabain to the membrane. In addition, we found that pool ATP alone functions together with bulk Na+ (without Mg2+) to release prebound ouabain. Curiously, ouabain was found to block bulk ATP from entering the pools. Finally, we show, with red cell inside-outside vesicles, that pool ATP alone supports the uptake of 45Ca by the Ca2+ pump, analogous to the Na+ pump uptake of 22Na in this circumstance. Although the membrane locus of the ATP pools within the membrane/cytoskeletal complex is unknown, it appears that pool ATP functions as the proximate energy source for the Na+ and Ca2+ pumps

    Unravelling Chemical Composition of Agave Spines: News from Agave fourcroydes Lem.

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    Spines are key plant modifications developed to deal against herbivores; however, its physical structure and chemical composition have been little explored in plant species. Here, we took advantage of high-throughput chromatography to characterize chemical composition of Agave fourcroydes Lem. spines, a species traditionally used for fiber extraction. Analyses of structural carbohydrate showed that spines have lower cellulose content than leaf fibers (52 and 72%, respectively) but contain more than 2-fold the hemicellulose and 1.5-fold pectin. Xylose and galacturonic acid were enriched in spines compared to fibers. The total lignin content in spines was 1.5-fold higher than those found in fibers, with elevated levels of syringyl (S) and guaiacyl (G) subunits but similar S/G ratios within tissues. Metabolomic profiling based on accurate mass spectrometry revealed the presence of phenolic compounds including quercetin, kaempferol, (+)-catechin, and (-)-epicatechin in A. fourcroydes spines, which were also detected in situ in spines tissues and could be implicated in the color of these plants' structures. Abundance of (+)-catechins could also explain proanthocyanidins found in spines. Agave spines may become a plant model to obtain more insights about cellulose and lignin interactions and condensed tannin deposition, which is valuable knowledge for the bioenergy industry and development of naturally dyed fibers, respectively
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