Institute Investigacion

Valencia, Spain

Institute Investigacion

Valencia, Spain
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Llorente-Folch I.,Autonomous University of Madrid | Llorente-Folch I.,Research Center Biomedica En Red Of Enfermedades Raras | Llorente-Folch I.,Institute Investigacion | Rueda C.B.,Autonomous University of Madrid | And 12 more authors.
Journal of Neuroscience | Year: 2016

ARALAR/AGC1/Slc25a12, the aspartate-glutamate carrier from brain mitochondria, is the regulatory step in the malate-aspartate NADH shuttle, MAS. MAS is used to oxidize cytosolic NADH in mitochondria, a process required to maintain oxidative glucose utilization. The role of ARALAR was analyzed in two paradigms of glutamate-induced excitotoxicity in cortical neurons: glucose deprivation and acute glutamate stimulation. ARALAR deficiency did not aggravate glutamate-induced neuronal death in vitro, although glutamate-stimulated respiration was impaired. In contrast, the presence of L-lactate as an additional source protected against glutamate-induced neuronal death in control, but not ARALAR-deficient neurons. L-Lactate supplementation increased glutamate-stimulated respiration partially prevented the decrease in the cytosolic ATP/ADP ratio induced by glutamate and substantially diminished mitochondrial accumulation of 8-oxoguanosine, a marker of reactive oxygen species production, only in the presence, but not the absence, of ARALAR. In addition, L-lactate potentiated glutamate-induced increase in cytosolic Ca2+, in a way independent of the presence of ARALAR. Interestingly, in vivo, the loss of half-a-dose of ARALAR inaralar+/− mice enhanced kainic acid-induced seizures and neuronal damage with respect to control animals, in a model of excitotoxicity in which increased L-lactate levels and L-lactate consumption have been previously proven. These results suggest that, in vivo, an inefficient operation of the shuttle in the aralar hemizygous mice prevents the protective role of L-lactate on glutamate excitotoxiciy and that the entry and oxidation of L-lactate through ARALAR-MAS pathway is required for its neuroprotective function. SIGNIFICANCE STATEMENT Lactate now stands as a metabolite necessary for multiple functions in the brain and is an alternative energy source during excitotoxic brain injury. Here we find that the absence of a functional malate-aspartate NADH shuttle caused by aralar/AGC1 disruption causes a block in lactate utilization by neurons, which prevents the protective role of lactate on excitotoxicity, but not glutamate excitotoxicity itself. Thus, failure to use lactate is detrimental and is possibly responsible for the exacerbated in vivo excitotoxicity in aralar+/− mice. © 2016 the authors.

Portillo B.C.,El Bosque University | Moreno J.E.,Instituto Nacional Of Salud | Yomayusa N.,Clinica Colsanitas S.A. | Alvarez C.A.,Clinica Colsanitas S.A. | And 9 more authors.
International Journal of Infectious Diseases | Year: 2013

Objective: To determine the molecular epidemiology and presence of virulence genes in community-acquired (CA) and hospital-acquired (HA) methicillin-resistant Staphylococcus aureus (MRSA) isolates and their relationship to clinical outcomes. Methods: An observational and prospective study of infections caused by MRSA was conducted between June 2006 and December 2007 across seven hospitals in three Colombian cities. MRSA isolates were analyzed for SCC. mec. Also, pulsed-field gel electrophoresis and multilocus sequence typing were performed and 25 virulence genes were identified. Results: Two hundred and seventy isolates were collected from 262 adult hospital patients with MRSA infections. Overall, 68% of the isolates were classified as HA-MRSA and 32% as CA-MRSA. We identified differences in the patterns of virulence genes: 85% of HA-MRSA isolates possessed the enterotoxin gene cluster (egc), whereas 92% of CA-MRSA isolates possessed the lukF-PV/lukS-PV genes. Multivariate analysis showed an increased risk of mortality for seg (p=0.001, odds ratio 4.73) and a protective effect for eta (p=0.018, odds ratio 0.33). Conclusions: Our study confirms that three clones of MRSA predominantly circulate in Colombia: a Chilean clone, a pediatric clone that causes HA-MRSA infections, and a USA300-related clone (SCC. mec IVc) in CA-MRSA infections, which differ in the content of clinically important virulence genes. This study confirms that PVL is not a determinant of severity or mortality in CA-MRSA infections. © 2013 International Society for Infectious Diseases.

Roma-Mateo C.,Institute Investigacion | Roma-Mateo C.,University of Valencia | Aguado C.,Research Center Biomedica En Red Of Enfermedades Raras | Aguado C.,Research Center Principe Felipe | And 10 more authors.
Free Radical Biology and Medicine | Year: 2015

Lafora disease (LD; OMIM 254780, ORPHA501) is a devastating neurodegenerative disorder characterized by the presence of glycogen-like intracellular inclusions called Lafora bodies and caused, in most cases, by mutations in either the EPM2A or the EPM2B gene, encoding respectively laforin, a phosphatase with dual specificity that is involved in the dephosphorylation of glycogen, and malin, an E3-ubiquitin ligase involved in the polyubiquitination of proteins related to glycogen metabolism. Thus, it has been reported that laforin and malin form a functional complex that acts as a key regulator of glycogen metabolism and that also plays a crucial role in protein homeostasis (proteostasis). Regarding this last function, it has been shown that cells are more sensitive to ER stress and show defects in proteasome and autophagy activities in the absence of a functional laforin-malin complex. More recently, we have demonstrated that oxidative stress accompanies these proteostasis defects and that various LD models show an increase in reactive oxygen species and oxidative stress products together with a dysregulated antioxidant enzyme expression and activity. In this review we discuss possible connections between the multiple defects in protein homeostasis present in LD and oxidative stress. ©2015PublishedbyElsevierInc.

Mateo-Moriones A.,Institute Investigacion | Villafuerte R.,Institute Investigacion | Ferreras P.,Institute Investigacion
Ibis | Year: 2012

A better knowledge of chick survival rates is required to enable understanding of the population dynamics of gamebirds and to develop management measures to conserve their populations. The Red-legged Partridge Alectoris rufa is a highly valued game species in Spain but its populations have declined in recent decades. A lack of appropriate monitoring methods has been a limitation in gaining information on the mortality of Red-legged Partridge chicks. We developed methods for the effective radiotagging of chicks in captivity and applied these methods in the field in northern Spain to estimate survival during the first 5 months of life. The most effective method for radiotagging captive chicks between 3 and 8 days old involved gluing small tags directly to the skin in the interscapular space using cyanoacrylate adhesive. Backpack harness tags attached with elastic bands were the most effective method of radiotagging 4-week-old chicks. Predation was the main cause of chick mortality identified during the field experiments. Survival between hatching and 5 months of age was estimated to be 16-21%. The lowest survival rates occurred during the first 7 days of life (62-70% cumulative survival) and this period seems to be a major determinant in the life history of the species. © 2012 The Authors. Ibis © 2012 British Ornithologists' Union.

Hospital readmissions are common and expensive, and there is little information on the problem in Colombia. The objective was to determine the frequency of 30-day all-cause hospital readmissions and associated factors. This was a retrospective analytical cohort study of 64,969 hospitalizations from January 2008 to January 2009 in 47 Colombian cities. 6,573 hospital readmissions, prevalence: 10.1% (men 10.9%, women 9.5%), 44.7% > 65 years of age. Hospital readmissions was associated with higher mortality (5.8% vs. 1.8%). There was an increase in the Hospital readmissions rate in patients with diseases of the circulatory system. Hospital readmissions was more likely in hematological diseases and neoplasms. Mean length of stay during the first readmission was 7 days in patients that were readmitted and 4.5 in those without readmission. Greater total cost of hospital readmissions (USA 21,998,275): 15.8% of the total cost of hospitalizations. Higher prevalence rates in referred patients (18.8%) and patients from the outpatient clinic (13.7%). Hospital readmissions is common and is associated with longer length of hospital stay and higher mortality and cost. Increased risk of hospital readmissions in men > 65 years, patients referred from other institutions, and in hematological diseases and neoplasms. © 2016, Fundacao Oswaldo Cruz. All rights reserved.

Krall P.,Institute Investigacion | Krall P.,Institute Investigacion Carlos III | Pineda C.,Institute Investigacion | Ruiz P.,Institute Investigacion | And 9 more authors.
Pediatric Nephrology | Year: 2014

Background: Genetic diagnosis of autosomal recessive polycystic kidney disease (ARPKD) is challenging due to the length and allelic heterogeneity of the PKHD1 gene. Mutations appear to be clustered at specific exons, depending on the geographic origin of the patient. We aimed to identify the PKHD1 exons most likely mutated in Spanish ARPKD patients. Methods: Mutation analysis was performed in 50 ARPKD probands and nine ARPKD-suspicious patients by sequencing PKHD1 exons arranged by their reported mutation frequency. Haplotypes containing the most frequent mutations were analyzed. Other PKD genes (HNF1B, PKD1, PKD2) were sequenced in PKHD1-negative cases. Results: Thirty-six different mutations (concentrated in 24 PKHD1 exons) were detected, giving a mutation detection rate of 86 %. The screening of five exons (58, 32, 34, 36, 37) yielded a 54 % chance of detecting one mutation; the screening of nine additional exons (3, 9, 39, 61, 5, 22, 26, 41, 57) increased the chance to 76 %. The c.9689delA mutation was present in 17 (34 %) patients, all of whom shared the same haplotype. Two HNF1B mutations and one PKD1 variant were detected in negative cases. Conclusions: Establishing a PKHD1 exon mutation profile in a specific population and starting the analysis with the most likely mutated exons might significantly enhance the efficacy of genetic testing in ARPKD. Analysis of other PKD genes might be considered, especially in suspicious cases. © 2013 IPNA.

Martinez-Ferri E.,Institute Investigacion | Muriel-Fernandez J.L.,Institute Investigacion | Diaz J.A.R.,University of Cordoba, Spain
Outlook on Agriculture | Year: 2013

The physically based agro-hydrological Soil, Water, Atmosphere and Plant (SWAP) model was applied in Andalucía (southern Spain) to simulate the water balance components in an irrigated citrus orchard. Direct measurements of soil water status using a frequency domain reflectometry (FDR) probe were used to calibrate the soil hydraulic functions using PEST, a parameter estimation package, and for crop coefficient (Kc) estimation. Model calibration and evaluation were carried out in 2008 using data from a citrus orchard considered representative of the typical agricultural practices in Andalucía. The SWAP model outputs agreed well with corresponding measured values in simulating soil water dynamics in-field. The model can be used in support of developing appropriate irrigation strategies for sustainable water management. An illustrative application using SWAP to assess the impacts of climate change on citrus production suggested increases in irrigation requirement of +6% to +16% for selected emissions scenarios for the 2050s and 2080s.

Arcas N.,Technical University of Cartagena | Alcon F.,Technical University of Cartagena | Gomez-Limon J.A.,Institute Investigacion | de Miguel M.D.,Technical University of Cartagena
Spanish Journal of Agricultural Research | Year: 2010

This work analyses the main research trends (subjects, methodology used, countries of the authors and data) in the economics of irrigation water during the last 10 years (2000-2009). For this purpose, a quantitative methodology has been used which is new to this sphere, based on the review of a representative sample of 332 papers published in the 15 most important journals focused on this field of science indexed in the databases of the Institute for Scientific Information (ISI), the Science Citation Index (SCI) and the Social Science Citation Index (SCCI). The results obtained confirm: a) the notable growth in the number of papers published, especially in the last three years, b) the high degree of collaboration between authors, including those of different origin, for their performance c) the prominence of the USA, Australia, India and Spain as the countries of the first authors and origin of the data, d) the greater attention given to subjects related with «investment project analysis», «production planning» and, especially, «production function and productivity of water», and e) the predominance of empirical studies that use basic analysis approaches (cost analysis, investment evaluation, etc.).

Matanza J.,Institute Investigacion | Alexandres S.,Comillas Pontifical University | Rodriguez-Morcillo C.,Institute Investigacion
2012 IEEE International Symposium on Power Line Communications and Its Applications, ISPLC 2012 | Year: 2012

The presented paper addresses the problem of impulsive noise interferences in Power Line Communication (PLC) systems. In order to provide a realistic scenario, a popular narrow band PLC solution has been chosen: PRIME. System's performance is evaluated under different impulsive noise environments. Simulations show how, even when the high-powerful time impulses hits a few signal samples, the noise energy corrupts most of the symbol in the OFDM spectrum. This affects directly the performance in terms of BER vs. SNR despite using the most robust communication mode in PRIME. Additionally, two common techniques are proposed to increase the performance under this kind of disturbances. The paper shows detailed figures with the improvement and a discussion of their usability. © 2012 IEEE.

Celio Alves P.,University of Porto | Pinheiro I.,University of Porto | Godinho R.,University of Porto | Vicente J.,Institute Investigacion | And 2 more authors.
Biological Journal of the Linnean Society | Year: 2010

The Eurasian wild boar, Sus scrofa, is an important game species and is widely distributed in Eurasia. The recent demographic expansions allied to man mediated translocations and reintroductions, reshaped the genetic variability of wild boar populations, and gave rise to management problems. Genetic variability and the population structure of the European populations are not well-known, in particular in the Iberian Peninsula. In the present study, we assessed the phylogenetic relationship among 17 Iberian wild boar populations and several Eurasian wild and domestic pigs by sequencing 660 bp of the mitochondrial (mt)DNA control region. This analysis was extended to the two autochthonous Portuguese pig breeds, Bísaro and Alentejano, and their relationship with Eurasian pigs was also established. High levels of gene diversity were found in Iberian wild boar and Portuguese domestic pigs, as well as a significant genetic difference among and within populations. Iberian wild boar and Portuguese pig breeds belong to the main European clade but diverge with animals from Central Europe, showing a high proportion of private (Iberian) haplotypes. These results suggest the existence of glacial refugia for Sus scrofa in the Iberian Peninsula during the Last Glacial Maximum. No signs of Asian mtDNA introgression from Asian populations were found in the present survey. © 2010 The Linnean Society of London.

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