45 results on '"Tornero, A"'
Search Results
2. Taguatagua 3: A new late Pleistocene settlement in a highly suitable lacustrine habitat in central Chile (34°S).
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Rafael Labarca, Matías Frugone-Álvarez, Liz Vilches, José Francisco Blanco, Ángela Peñaloza, Carolina Godoy-Aguirre, Álvaro Lizama-Catalán, Cristóbal Oyarzo, Carlos Tornero, Erwin González-Guarda, Ayelen Delgado, Marcela Sepúlveda, and Paula Soto-Huenchuman
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Medicine ,Science - Abstract
We present the results of the excavations and analyses of the diverse and exceptional archaeological assemblage of Taguatagua 3, a new late Pleistocene site located in the ancient Tagua Tagua lake in Central Chile (34°S). The anthropogenic context is constrained in a coherently dated stratigraphic deposit which adds new information about the mobility, subsistence strategies, and settlement of the early hunter-gatherers of southern South America. The age model constructed, as well as radiocarbon dates obtained directly from a combustion structure, indicate that the human occupation occurred over a brief time span around 12,440-12,550 cal yr BP. Considering taphonomic, geoarchaeological, lithic, archaeobotanical, and zooarchaeological evidence, as well as the spatial distribution combined with ethnographic data, we interpret Taguatagua 3 as a logistic and temporary camp associated mainly with gomphothere hunting and butchering. Nevertheless, several other activities were carried out here as well, such as hide and/or bone preparation, small vertebrate and plant processing and consumption, and red ochre grinding. Botanical and eggshell remains suggest that the anthropic occupation occurred during the dry season. Considering the contemporaneous sites recorded in the basin, we conclude that the ancient Tagua Tagua lake was a key location along the region's early hunter-gatherer mobility circuits. In this context, it acted as a recurrent hunting/scavenging place during the Late Pleistocene due to its abundant, diverse, and predictable resources.
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- 2024
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3. Taguatagua 3: A new late Pleistocene settlement in a highly suitable lacustrine habitat in central Chile (34°S)
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Labarca, Rafael, primary, Frugone-Álvarez, Matías, additional, Vilches, Liz, additional, Blanco, José Francisco, additional, Peñaloza, Ángela, additional, Godoy-Aguirre, Carolina, additional, Lizama-Catalán, Álvaro, additional, Oyarzo, Cristóbal, additional, Tornero, Carlos, additional, González-Guarda, Erwin, additional, Delgado, Ayelen, additional, Sepúlveda, Marcela, additional, and Soto-Huenchuman, Paula, additional
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- 2024
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4. The complex landscape of TMS devices: A brief overview
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Ane Miren Gutiérrez-Muto, Sven Bestmann, Rubén Sánchez de la Torre, José L. Pons, Antonio Oliviero, and Jesús Tornero
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Medicine ,Science - Published
- 2023
5. The complex landscape of TMS devices: A brief overview
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Gutiérrez-Muto, Ane Miren, primary, Bestmann, Sven, additional, Sánchez de la Torre, Rubén, additional, Pons, José L., additional, Oliviero, Antonio, additional, and Tornero, Jesús, additional
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- 2023
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6. Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers.
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Blanco, Ignacio, Kuchenbaecker, Karoline, Cuadras, Daniel, Wang, Xianshu, Barrowdale, Daniel, de Garibay, Gorka, Librado, Pablo, Sánchez-Gracia, Alejandro, Rozas, Julio, Bonifaci, Núria, McGuffog, Lesley, Pankratz, Vernon, Islam, Abul, Mateo, Francesca, Berenguer, Antoni, Petit, Anna, Català, Isabel, Brunet, Joan, Feliubadaló, Lidia, Tornero, Eva, Benítez, Javier, Osorio, Ana, Ramón y Cajal, Teresa, Nevanlinna, Heli, Aittomäki, Kristiina, Arun, Banu, Toland, Amanda, Karlan, Beth, Walsh, Christine, Lester, Jenny, Greene, Mark, Mai, Phuong, Nussbaum, Robert, Andrulis, Irene, Domchek, Susan, Nathanson, Katherine, Rebbeck, Timothy, Barkardottir, Rosa, Jakubowska, Anna, Lubinski, Jan, Durda, Katarzyna, Jaworska-Bieniek, Katarzyna, Claes, Kathleen, Van Maerken, Tom, Díez, Orland, Hansen, Thomas, Jønson, Lars, Gerdes, Anne-Marie, Ejlertsen, Bent, de la Hoya, Miguel, Caldés, Trinidad, Dunning, Alison, Oliver, Clare, Fineberg, Elena, Cook, Margaret, Peock, Susan, McCann, Emma, Murray, Alex, Jacobs, Chris, Pichert, Gabriella, Lalloo, Fiona, Chu, Carol, Dorkins, Huw, Paterson, Joan, Ong, Kai-Ren, Teixeira, Manuel, Hogervorst, Frans, van der Hout, Annemarie, Seynaeve, Caroline, van der Luijt, Rob, Ligtenberg, Marjolijn, Devilee, Peter, Wijnen, Juul, Rookus, Matti, Meijers-Heijboer, Hanne, Blok, Marinus, van den Ouweland, Ans, Aalfs, Cora, Rodriguez, Gustavo, Phillips, Kelly-Anne, Piedmonte, Marion, Nerenstone, Stacy, Bae-Jump, Victoria, OMalley, David, Ratner, Elena, Schmutzler, Rita, Wappenschmidt, Barbara, Rhiem, Kerstin, Engel, Christoph, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Plendl, Hansjoerg, Niederacher, Dieter, Sutter, Christian, Wang-Gohrke, Shan, Steinemann, Doris, Preisler-Adams, Sabine, Kast, Karin, and Varon-Mateeva, Raymonda
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Aurora Kinase A ,Breast Neoplasms ,Carcinogenesis ,Cell Cycle Proteins ,Estrogen Receptor alpha ,Evolution ,Molecular ,Extracellular Matrix Proteins ,Female ,Genes ,BRCA1 ,Genes ,BRCA2 ,Genetic Loci ,Genetic Predisposition to Disease ,Humans ,Hyaluronan Receptors ,Likelihood Functions ,Mammary Glands ,Human ,Microtubule-Associated Proteins ,Mutation ,Nuclear Proteins ,Polymorphism ,Single Nucleotide ,Retrospective Studies ,Tubulin - Abstract
While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04-1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03-1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteraction values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.
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- 2015
7. Investigating Neolithic caprine husbandry in the Central Pyrenees: Insights from a multi-proxy study at Els Trocs cave (Bisaurri, Spain).
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Cristina Tejedor-Rodríguez, Marta Moreno-García, Carlos Tornero, Alizé Hoffmann, Íñigo García-Martínez de Lagrán, Héctor Arcusa-Magallón, Rafael Garrido-Pena, José Ignacio Royo-Guillén, Sonia Díaz-Navarro, Leonor Peña-Chocarro, Kurt W Alt, and Manuel Rojo-Guerra
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Medicine ,Science - Abstract
Sheep remains constitute the main archaeozoological evidence for the presence of Early Neolithic human groups in the highlands of the Southern Pyrenees but understanding the role of herding activities in the Neolithisation process of this mountain ecosystem calls for the analysis of large and well-dated faunal assemblages. Cova de Els Trocs (Bisaurri, Huesca, Spain), a cave located at 1564 m a.s.l on the southern slopes of the Central Pyrenees, is an excellent case study since it was seasonally occupied throughout the Neolithic (ca. 5312-2913 cal. BC) and more than 4000 caprine remains were recovered inside. The multi-proxy analytical approach here presented has allowed us to offer new data elaborating on vertical mobility practices and herd management dynamics as has not been attempted up until now within Neolithic high-mountain sites in the Iberian Peninsula. For the first time, δ18O and δ13C stable isotope analyses offer direct evidence on both the regular practice of altitudinal movements of sheep flocks and the extended breeding season of sheep. Autumn births are recorded from the second half of the fifth millennium cal. BC onwards. Age-at-death distributions illustrate the progressive decline in caprine perinatal mortality together with the rising survival rate of individuals older than six months of age and the larger frequency of adults. This trend alongside the 'off-season' lambing signal at the implementation of husbandry techniques over time, probably aiming to increase the size of the flocks and their productivity. Palaeoparasitological analyses of sediment samples document also the growing reliance on herding activities of the human groups visiting the Els Trocs cave throughout the Neolithic sequence. In sum, our work provides substantial arguments to conclude that the advanced herding management skills of the Early Neolithic communities arriving in Iberia facilitated the anthropisation process of the subalpine areas of the Central Pyrenees.
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- 2021
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8. Efficacy of Sphincter Control Training and medical device in the treatment of premature ejaculation: A multicenter randomized controlled clinical trial.
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Jesús E Rodríguez, Jose A Picazo, Juan C Marzo, José A Piqueras, Leandro Reina, Guillermo Hidalgo, and Guillermo Tornero
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Medicine ,Science - Abstract
A new line of treatment for premature ejaculation (PE) based on the use of masturbation aid device in combination with behavioral techniques has emerged in recent years. We report a multicenter randomized clinical trial with a parallel group design to determine the effectiveness of an electronic device called Myhixel I© in the treatment of PE. Forty patients who met the criteria for the diagnosis of lifelong PE, were assigned to two treatment groups completed the Sphincter control training (SCT) program in eight weeks. The only difference between groups was the use of the device. The main measure was the "fold increase" (FI) of the intravaginal ejaculatory latency time (IELT). The geometric means of IELT show, at the end of the treatment at week 8, a superiority of the device group. The mean FI 4.27 (SD 2.59) at the end of treatment for the device group was clearly higher than obtained in the previous clinical trial, in which a specific medical device was not used. No side effects were observed and it required little therapeutic input and no partner involvement. The SCT program in combination with the Myhixel I© is an effective treatment for PE.
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- 2021
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9. Correction: Taguatagua 3: A new late Pleistocene settlement in a highly suitable lacustrine habitat in central Chile (34°S).
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Labarca, Rafael, Frugone-Álvarez, Matías, Vilches, Liz, Francisco Blanco, José, Peñaloza, Ángela, Godoy-Aguirre, Carolina, Lizama-Catalán, Álvaro, Oyarzo, Cristóbal, Tornero, Carlos, González-Guarda, Erwin, Delgado, Ayelen, Sepúlveda, Marcela, and Soto-Huenchuman, Paula
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PLEISTOCENE Epoch ,HABITATS ,FACIES ,ASTRAGALUS (Plants) ,VERTEBRAE - Abstract
This document is a correction notice for an article titled "Taguatagua 3: A new late Pleistocene settlement in a highly suitable lacustrine habitat in central Chile (34°S)" published in the journal PLoS ONE. The correction states that the images for Figures 4 and 5 in the article were incorrectly switched. The correct figures and their captions are provided in the correction notice. The figures depict the relative frequencies of faunal remains and taphonomic modifications, as well as taphonomic modifications on gomphothere bones. The authors of the article are listed as Rafael Labarca, Matías Frugone-Álvarez, Liz Vilches, José Francisco Blanco, Ángela Peñaloza, Carolina Godoy-Aguirre, Álvaro Lizama-Catalán, Cristóbal Oyarzo, Carlos Tornero, Erwin González-Guarda, Ayelen Delgado, Marcela Sepúlveda, and Paula Soto-Huenchuman. [Extracted from the article]
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- 2024
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10. Surface respiratory electromyography and dyspnea in acute heart failure patients.
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Daniele Luiso, Jair A Villanueva, Laia C Belarte-Tornero, Aleix Fort, Zorba Blázquez-Bermejo, Sonia Ruiz, Ramon Farré, Jordi Rigau, Julio Martí-Almor, and Núria Farré
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Medicine ,Science - Abstract
INTRODUCTION AND OBJECTIVES:Dyspnea is the most common symptom among hospitalized patients with heart failure (HF) but besides dyspnea questionnaires (which reflect the subjective patient sensation and are not fully validated in HF) there are no measurable physiological variables providing objective assessment of dyspnea in a setting of acute HF patients. Studies performed in respiratory patients suggest that the measurement of electromyographic (EMG) activity of the respiratory muscles with surface electrodes correlates well with dyspnea. Our aim was to test the hypothesis that respiratory muscles EMG activity is a potential marker of dyspnea severity in acute HF patients. METHODS:Prospective and descriptive pilot study carried out in 25 adult patients admitted for acute HF. Measurements were carried out with a cardio-respiratory portable polygraph including EMG surface electrodes for measuring the activity of main (diaphragm) and accessory (scalene and pectoralis minor) respiratory muscles. Dyspnea sensation was assessed by means of the Likert 5 questionnaire. Data were recorded during 3 min of spontaneous breathing and after breathing at maximum effort for several cycles for normalizing data. An index to quantify the activity of each respiratory muscle was computed. This assessment was carried out within the first 24 h of admission, and at day 2 and 5. RESULTS:Dyspnea score decreased along the three measured days. Diaphragm and scalene EMG index showed a positive and significant direct relationship with dyspnea score (p
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- 2020
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11. Prefiltering based on experimental paradigm for analysis of fMRI complex brain networks.
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Salvador Jiménez, Laura Rotger, Carlos Aguirre, Alberto Muñoz, Sergio Granados, and Jesús Tornero
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Medicine ,Science - Abstract
Brain networks offers a new insight about connections between function and anatomical regions of human brain. We present results from brain networks built from functional magnetic resonance images during finger tapping paradigm. Pearson voxel-voxel correlation in time and frequency domains were performed for all subjects. Besides this standard framework we have implemented a new approach consisting in filtering the data with respect to the fMRI paradigm (finger tapping) in order to obtain a better understanding of the network involved in the execution of the task. The main topological graph measures have been compared in both cases: voxel-voxel correlation and voxel-paradigm filtering plus voxel-voxel correlation. With the standard voxel-voxel correlation a clearly free-scale network was obtained. On the other hand, when we prefiltered the paradigm we obtained two different kind of networks: 1) free-scale; 2) random-like. To our best knowledge, this behaviour is reported here for first time for brain networks. We suggest that paradigm signal prefiltering can provide more infomation about the brain networks.
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- 2020
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12. NPR1 paralogs of Arabidopsis and their role in salicylic acid perception.
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María José Castelló, Laura Medina-Puche, Julián Lamilla, and Pablo Tornero
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Medicine ,Science - Abstract
Salicylic acid (SA) is responsible for certain plant defence responses and NON EXPRESSER OF PATHOGENESIS RELATED 1 (NPR1) is the master regulator of SA perception. In Arabidopsis thaliana there are five paralogs of NPR1. In this work we tested the role of these paralogs in SA perception by generating combinations of mutants and transgenics. NPR2 was the only paralog able to partially complement an npr1 mutant. The null npr2 reduces SA perception in combination with npr1 or other paralogs. NPR2 and NPR1 interacted in all the conditions tested, and NPR2 also interacted with other SA-related proteins as NPR1 does. The remaining paralogs behaved differently in SA perception, depending on the genetic background, and the expression of some of the genes induced by SA in an npr1 background was affected by the presence of the paralogs. NPR2 fits all the requirements of an SA receptor while the remaining paralogs also work as SA receptors with a strong hierarchy. According to the data presented here, the closer the gene is to NPR1, the more relevant its role in SA perception.
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- 2018
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13. Attenuation of reactive gliosis in stroke-injured mouse brain does not affect neurogenesis from grafted human iPSC-derived neural progenitors.
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Cecilia Laterza, Naomi Uoshima, Daniel Tornero, Ulrika Wilhelmsson, Anna Stokowska, Ruimin Ge, Milos Pekny, Olle Lindvall, and Zaal Kokaia
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Medicine ,Science - Abstract
Induced pluripotent stem cells (iPSCs) or their progeny, derived from human somatic cells, can give rise to functional improvements after intracerebral transplantation in animal models of stroke. Previous studies have indicated that reactive gliosis, which is associated with stroke, inhibits neurogenesis from both endogenous and grafted neural stem/progenitor cells (NSPCs) of rodent origin. Here we have assessed whether reactive astrocytes affect the fate of human iPSC-derived NSPCs transplanted into stroke-injured brain. Mice with genetically attenuated reactive gliosis (deficient for GFAP and vimentin) were subjected to cortical stroke and cells were implanted adjacent to the ischemic lesion one week later. At 8 weeks after transplantation, immunohistochemical analysis showed that attenuated reactive gliosis did not affect neurogenesis or commitment towards glial lineage of the grafted NSPCs. Our findings, obtained in a human-to-mouse xenograft experiment, provide evidence that the reactive gliosis in stroke-injured brain does not affect the formation of new neurons from intracortically grafted human iPSC-derived NSPCs. However, for a potential clinical translation of these cells in stroke, it will be important to clarify whether the lack of effect of reactive gliosis on neurogenesis is observed also in a human-to-human experimental setting.
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- 2018
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14. Dispersal mode and spatial extent influence distance-decay patterns in pond metacommunities.
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Irene Tornero, Dani Boix, Simonetta Bagella, Carla Pinto-Cruz, Maria Carmela Caria, Anabela Belo, Ana Lumbreras, Jordi Sala, Jordi Compte, and Stéphanie Gascón
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Medicine ,Science - Abstract
Assuming that dispersal modes or abilities can explain the different responses of organisms to geographic or environmental distances, the distance-decay relationship is a useful tool to evaluate the relative role of local environmental structuring versus regional control in community composition. Based on continuing the current theoretical framework on metacommunity dynamics and based on the predictive effect of distance on community similarity, we proposed a new framework that includes the effect of spatial extent. In addition, we tested the validity of our proposal by studying the community similarity among three biotic groups with different dispersal modes (macrofaunal active and passive dispersers and plants) from two pond networks, where one network had a small spatial extent, and the other network had an extent that was 4 times larger. Both pond networks have similar environmental variability. Overall, we found that environmental distance had larger effects than geographical distances in both pond networks. Moreover, our results suggested that species sorting is the main type of metacommunity dynamics shaping all biotic groups when the spatial extent is larger. In contrast, when the spatial extent is smaller, the observed distance-decay patterns suggested that different biotic groups were mainly governed by different metacommunity dynamics. While the distance-decay patterns of active dispersers better fit the trend that was expected when mass effects govern a metacommunity, passive dispersers showed a pattern that was expected when species sorting prevails. Finally, in the case of plants, it is difficult to associate their distance-decay patterns with one type of metacommunity dynamics.
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- 2018
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15. Genetic variation associated with cardiovascular risk in autoimmune diseases.
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Pedro P Perrotti, Adrià Aterido, Antonio Fernández-Nebro, Juan D Cañete, Carlos Ferrándiz, Jesús Tornero, Javier P Gisbert, Eugeni Domènech, Benjamín Fernández-Gutiérrez, Fernando Gomollón, Esther García-Planella, Emilia Fernández, Raimon Sanmartí, Jordi Gratacós, Víctor Manuel Martínez-Taboada, Luís Rodríguez-Rodríguez, Núria Palau, Raül Tortosa, Mireia L Corbeto, María L Lasanta, Sara Marsal, Antonio Julià, and IMID Consortium
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Medicine ,Science - Abstract
Autoimmune diseases have a higher prevalence of cardiovascular events compared to the general population. The objective of this study was to investigate the genetic basis of cardiovascular disease (CVD) risk in autoimmunity. We analyzed genome-wide genotyping data from 6,485 patients from six autoimmune diseases that are associated with a high socio-economic impact. First, for each disease, we tested the association of established CVD risk loci. Second, we analyzed the association of autoimmune disease susceptibility loci with CVD. Finally, to identify genetic patterns associated with CVD risk, we applied the cross-phenotype meta-analysis approach (CPMA) on the genome-wide data. A total of 17 established CVD risk loci were significantly associated with CVD in the autoimmune patient cohorts. From these, four loci were found to have significantly different genetic effects across autoimmune diseases. Six autoimmune susceptibility loci were also found to be associated with CVD risk. Genome-wide CPMA analysis identified 10 genetic clusters strongly associated with CVD risk across all autoimmune diseases. Two of these clusters are highly enriched in pathways previously associated with autoimmune disease etiology (TNFα and IFNγ cytokine pathways). The results of this study support the presence of specific genetic variation associated with the increase of CVD risk observed in autoimmunity.
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- 2017
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16. β-carbonic anhydrases play a role in salicylic acid perception in Arabidopsis.
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Laura Medina-Puche, María José Castelló, Juan Vicente Canet, Julián Lamilla, María Laura Colombo, and Pablo Tornero
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Medicine ,Science - Abstract
The plant hormone salicylic acid (SA) is required for defense responses. NON EXPRESSER OF PATHOGENESIS RELATED 1 (NPR1) and NON RECOGNITION OF BTH-4 (NRB4) are required for the response to SA in Arabidopsis (Arabidopsis thaliana). Here, we isolated several interactors of NRB4 using yeast two-hybrid assays. Two of these interactors, βCA1 and βCA2, are β-carbonic anhydrase family proteins. Since double mutant βca1 βca2 plants did not show any obvious phenotype, we investigated other βCAs and found that NRB4 also interacts with βCA3 and βCA4. Moreover, several βCAs interacted with NPR1 in yeast, including one that interacted in a SA-dependent manner. This interaction was abolished in loss-of-function alleles of NPR1. Interactions between βCAs and both NRB4 and NPR1 were also detected in planta, with evidence for a triple interaction, NRB4-βCA1-NPR1. The quintuple mutant βca1 βca2 βca3 βca4 βca6 showed partial insensitivity to SA. These findings suggest that one of the functions of carbonic anhydrases is to modulate the perception of SA in plants.
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- 2017
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17. Hidden α-helical propensity segments within disordered regions of the transcriptional activator CHOP.
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Ángeles Canales, Marcel Rösinger, Javier Sastre, Isabella C Felli, Jesús Jiménez-Barbero, Guillermo Giménez-Gallego, and Carlos Fernández-Tornero
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Medicine ,Science - Abstract
C/EBP-homologous protein (CHOP) is a key determinant of the apoptotic response to endoplasmic reticulum stress or DNA damage. As a member of the C/EBP family, CHOP contains a low complexity N-terminal region involved in transcriptional activation, followed by a bZIP that binds DNA after dimerization. However, in contrast to other C/EBPs, CHOP directs binding to non-canonical C/EBP sites due to unique substitutions in its DNA-binding domain. Herein, we show that the N-terminal region of CHOP is intrinsically unstructured but contains two segments presenting α-helical propensity. One of these segments is conserved in other C/EBPs and mediates essential roles of CHOP, including regulation through phosphorylation. The second segment is placed within a proteolytic-resistant portion of the protein and exhibits reduced flexibility. Moreover, the DNA-binding region of CHOP also contains a segment with α-helical character towards its most N-terminal part. Our results suggest that structure-prone segments scattered within disordered regions may be critical for macromolecular recognition during CHOP-mediated transcriptional activation.
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- 2017
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18. Variation at FCGR2A and functionally related genes is associated with the response to anti-TNF therapy in rheumatoid arthritis.
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Gabriela Avila-Pedretti, Jesús Tornero, Antonio Fernández-Nebro, Francisco Blanco, Isidoro González-Alvaro, Juan D Cañete, Joan Maymó, Mercedes Alperiz, Benjamín Fernández-Gutiérrez, Alex Olivé, Héctor Corominas, Alba Erra, Adrià Aterido, María López Lasanta, Raül Tortosa, Antonio Julià, and Sara Marsal
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Medicine ,Science - Abstract
ObjectiveAnti-TNF therapies have been highly efficacious in the management of rheumatoid arthritis (RA), but 25-30% of patients do not show a significant clinical response. There is increasing evidence that genetic variation at the Fc receptor FCGR2A is associated with the response to anti-TNF therapy. We aimed to validate this genetic association in a patient cohort from the Spanish population, and also to identify new genes functionally related to FCGR2A that are also associated with anti-TNF response.MethodsA total of 348 RA patients treated with an anti-TNF therapy were included and genotyped for FCGR2A polymorphism rs1081274. Response to therapy was determined at 12 weeks, and was tested for association globally and independently for each anti-TNF drug (infliximab, etanercept and adalimumab). Using gene expression profiles from macrophages obtained from synovial fluid of RA patients, we searched for genes highly correlated with FCGR2A expression. Tag SNPs were selected from each candidate gene and tested for association with the response to therapy.ResultsWe found a significant association between FCGR2A and the response to adalimumab (P=0.022). Analyzing the subset of anti-CCP positive RA patients (78%), we also found a significant association between FCGR2A and the response to infliximab (P=0.035). DHX32 and RGS12 were the most consistently correlated genes with FCGR2A expression in RA synovial fluid macrophages (PConclusionsIn the present study we have validated the FCGR2A association in an independent population, and we have identified new genes associated with the response to anti-TNF therapy in RA.
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- 2015
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19. Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers.
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Ignacio Blanco, Karoline Kuchenbaecker, Daniel Cuadras, Xianshu Wang, Daniel Barrowdale, Gorka Ruiz de Garibay, Pablo Librado, Alejandro Sánchez-Gracia, Julio Rozas, Núria Bonifaci, Lesley McGuffog, Vernon S Pankratz, Abul Islam, Francesca Mateo, Antoni Berenguer, Anna Petit, Isabel Català, Joan Brunet, Lidia Feliubadaló, Eva Tornero, Javier Benítez, Ana Osorio, Teresa Ramón y Cajal, Heli Nevanlinna, Kristiina Aittomäki, Banu K Arun, Amanda E Toland, Beth Y Karlan, Christine Walsh, Jenny Lester, Mark H Greene, Phuong L Mai, Robert L Nussbaum, Irene L Andrulis, Susan M Domchek, Katherine L Nathanson, Timothy R Rebbeck, Rosa B Barkardottir, Anna Jakubowska, Jan Lubinski, Katarzyna Durda, Katarzyna Jaworska-Bieniek, Kathleen Claes, Tom Van Maerken, Orland Díez, Thomas V Hansen, Lars Jønson, Anne-Marie Gerdes, Bent Ejlertsen, Miguel de la Hoya, Trinidad Caldés, Alison M Dunning, Clare Oliver, Elena Fineberg, Margaret Cook, Susan Peock, Emma McCann, Alex Murray, Chris Jacobs, Gabriella Pichert, Fiona Lalloo, Carol Chu, Huw Dorkins, Joan Paterson, Kai-Ren Ong, Manuel R Teixeira, Teixeira, Frans B L Hogervorst, Annemarie H van der Hout, Caroline Seynaeve, Rob B van der Luijt, Marjolijn J L Ligtenberg, Peter Devilee, Juul T Wijnen, Matti A Rookus, Hanne E J Meijers-Heijboer, Marinus J Blok, Ans M W van den Ouweland, Cora M Aalfs, Gustavo C Rodriguez, Kelly-Anne A Phillips, Marion Piedmonte, Stacy R Nerenstone, Victoria L Bae-Jump, David M O'Malley, Elena S Ratner, Rita K Schmutzler, Barbara Wappenschmidt, Kerstin Rhiem, Christoph Engel, Alfons Meindl, Nina Ditsch, Norbert Arnold, Hansjoerg J Plendl, Dieter Niederacher, Christian Sutter, Shan Wang-Gohrke, Doris Steinemann, Sabine Preisler-Adams, Karin Kast, Raymonda Varon-Mateeva, Andrea Gehrig, Anders Bojesen, Inge Sokilde Pedersen, Lone Sunde, Uffe Birk Jensen, Mads Thomassen, Torben A Kruse, Lenka Foretova, Paolo Peterlongo, Loris Bernard, Bernard Peissel, Giulietta Scuvera, Siranoush Manoukian, Paolo Radice, Laura Ottini, Marco Montagna, Simona Agata, Christine Maugard, Jacques Simard, Penny Soucy, Andreas Berger, Anneliese Fink-Retter, Christian F Singer, Christine Rappaport, Daphne Geschwantler-Kaulich, Muy-Kheng Tea, Georg Pfeiler, BCFR, Esther M John, Alex Miron, Susan L Neuhausen, Mary Beth Terry, Wendy K Chung, Mary B Daly, David E Goldgar, Ramunas Janavicius, Cecilia M Dorfling, Elisabeth J van Rensburg, Florentia Fostira, Irene Konstantopoulou, Judy Garber, Andrew K Godwin, Edith Olah, Steven A Narod, Gad Rennert, Shani Shimon Paluch, Yael Laitman, Eitan Friedman, SWE-BRCA, Annelie Liljegren, Johanna Rantala, Marie Stenmark-Askmalm, Niklas Loman, Evgeny N Imyanitov, Ute Hamann, kConFab Investigators, Amanda B Spurdle, Sue Healey, Jeffrey N Weitzel, Josef Herzog, David Margileth, Chiara Gorrini, Manel Esteller, Antonio Gómez, Sergi Sayols, Enrique Vidal, Holger Heyn, GEMO, Dominique Stoppa-Lyonnet, Melanie Léoné, Laure Barjhoux, Marion Fassy-Colcombet, Antoine de Pauw, Christine Lasset, Sandra Fert Ferrer, Laurent Castera, Pascaline Berthet, François Cornelis, Yves-Jean Bignon, Francesca Damiola, Sylvie Mazoyer, Olga M Sinilnikova, Christopher A Maxwell, Joseph Vijai, Mark Robson, Noah Kauff, Marina J Corines, Danylko Villano, Julie Cunningham, Adam Lee, Noralane Lindor, Conxi Lázaro, Douglas F Easton, Kenneth Offit, Georgia Chenevix-Trench, Fergus J Couch, Antonis C Antoniou, and Miguel Angel Pujana
- Subjects
Medicine ,Science - Abstract
While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04-1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03-1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteraction values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.
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- 2015
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20. Altered Expression of Wnt Signaling Pathway Components in Osteogenesis of Mesenchymal Stem Cells in Osteoarthritis Patients.
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Pilar Tornero-Esteban, Ascensión Peralta-Sastre, Eva Herranz, Luis Rodríguez-Rodríguez, Arkaitz Mucientes, Lydia Abásolo, Fernando Marco, Benjamín Fernández-Gutiérrez, and José Ramón Lamas
- Subjects
Medicine ,Science - Abstract
INTRODUCTION:Osteoarthritis (OA) is characterized by altered homeostasis of joint cartilage and bone, whose functional properties rely on chondrocytes and osteoblasts, belonging to mesenchymal stem cells (MSCs). WNT signaling acts as a hub integrating and crosstalking with other signaling pathways leading to the regulation of MSC functions. The aim of this study was to evaluate the existence of a differential signaling between Healthy and OA-MSCs during osteogenesis. METHODS:MSCs of seven OA patients and six healthy controls were isolated, characterised and expanded. During in vitro osteogenesis, cells were recovered at days 1, 10 and 21. RNA and protein content was obtained. Expression of WNT pathway genes was evaluated using RT-qPCR. Functional studies were also performed to study the MSC osteogenic commitment and functional and post-traslational status of β-catenin and several receptor tyrosine kinases. RESULTS:Several genes were downregulated in OA-MSCs during osteogenesis in vitro. These included soluble Wnts, inhibitors, receptors, co-receptors, several kinases and transcription factors. Basal levels of β-catenin were higher in OA-MSCs, but calcium deposition and expression of osteogenic genes was similar between Healthy and OA-MSCs. Interestingly an increased phosphorylation of p44/42 MAPK (ERK1/2) signaling node was present in OA-MSCs. CONCLUSION:Our results point to the existence in OA-MSCs of alterations in expression of Wnt pathway components during in vitro osteogenesis that are partially compensated by post-translational mechanisms modulating the function of other pathways. We also point the relevance of other signaling pathways in OA pathophysiology suggesting their role in the maintenance of joint homeostasis through modulation of MSC osteogenic potential.
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- 2015
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21. Equality in Educational Policy and the Heritability of Educational Attainment.
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Lucía Colodro-Conde, Frühling Rijsdijk, María J Tornero-Gómez, Juan F Sánchez-Romera, and Juan R Ordoñana
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Medicine ,Science - Abstract
Secular variation in the heritability of educational attainment are proposed to be due to the implementation of more egalitarian educational policies leading to increased equality in educational opportunities in the second part of the 20th century. The action of effect is hypothesized to be a decrease of shared environmental (e.g., family socioeconomic status or parents' education) influences on educational attainment, giving more room for genetic differences between individuals to impact on the variation of the trait. However, this hypothesis has not yet found consistent evidence. Support for this effect relies mainly on comparisons between countries adopting different educational systems or between different time periods within a country reflecting changes in general policy. Using a population-based sample of 1271 pairs of adult twins, we analyzed the effect of the introduction of a specific educational policy in Spain in 1970. The shared-environmental variance decreased, leading to an increase in heritability in the post-reform cohort (44 vs. 67%) for males. Unstandardized estimates of genetic variance were of a similar magnitude (.56 vs. .57) between cohorts, while shared environmental variance decreased from .56 to .04. Heritability remained in the same range for women (40 vs. 34%). Our results support the role of educational policy in affecting the relative weight of genetic and environmental factors on educational attainment, such that increasing equality in educational opportunities increases heritability estimates by reducing variation of non-genetic familial origin.
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- 2015
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22. Efficacy of Sphincter Control Training and medical device in the treatment of premature ejaculation: A multicenter randomized controlled clinical trial
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Rodríguez, Jesús E., primary, Picazo, Jose A., additional, Marzo, Juan C., additional, Piqueras, José A., additional, Reina, Leandro, additional, Hidalgo, Guillermo, additional, and Tornero, Guillermo, additional
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- 2021
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23. An allele of Arabidopsis COI1 with hypo- and hypermorphic phenotypes in plant growth, defence and fertility.
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Albor Dobón, Brande B H Wulff, Juan Vicente Canet, Patrocinio Fort, and Pablo Tornero
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Medicine ,Science - Abstract
Resistance to biotrophic pathogens is largely dependent on the hormone salicylic acid (SA) while jasmonic acid (JA) regulates resistance against necrotrophs. JA negatively regulates SA and is, in itself, negatively regulated by SA. A key component of the JA signal transduction pathway is its receptor, the COI1 gene. Mutations in this gene can affect all the JA phenotypes, whereas mutations in other genes, either in JA signal transduction or in JA biosynthesis, lack this general effect. To identify components of the part of the resistance against biotrophs independent of SA, a mutagenised population of NahG plants (severely depleted of SA) was screened for suppression of susceptibility. The screen resulted in the identification of intragenic and extragenic suppressors, and the results presented here correspond to the characterization of one extragenic suppressor, coi1-40. coi1-40 is quite different from previously described coi1 alleles, and it represents a strategy for enhancing resistance to biotrophs with low levels of SA, likely suppressing NahG by increasing the perception to the remaining SA. The phenotypes of coi1-40 lead us to speculate about a modular function for COI1, since we have recovered a mutation in COI1 which has a number of JA-related phenotypes reduced while others are equal to or above wild type levels.
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- 2013
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24. Functional and structural analysis of C-terminal BRCA1 missense variants.
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Francisco Quiles, Juana Fernández-Rodríguez, Roberto Mosca, Lídia Feliubadaló, Eva Tornero, Joan Brunet, Ignacio Blanco, Gabriel Capellá, Miquel Àngel Pujana, Patrick Aloy, Alvaro Monteiro, and Conxi Lázaro
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Medicine ,Science - Abstract
Germline inactivating mutations in BRCA1 and BRCA2 genes are responsible for Hereditary Breast and Ovarian Cancer Syndrome (HBOCS). Genetic testing of these genes is available, although approximately 15% of tests identify variants of uncertain significance (VUS). Classification of these variants into pathogenic or non-pathogenic type is an important challenge in genetic diagnosis and counseling. The aim of the present study is to functionally assess a set of 7 missense VUS (Q1409L, S1473P, E1586G, R1589H, Y1703S, W1718L and G1770V) located in the C-terminal region of BRCA1 by combining in silico prediction tools and structural analysis with a transcription activation (TA) assay. The in silico prediction programs gave discrepant results making its interpretation difficult. Structural analysis of the three variants located in the BRCT domains (Y1703S, W1718L and G1770V) reveals significant alterations of BRCT structure. The TA assay shows that variants Y1703S, W1718L and G1770V dramatically compromise the transcriptional activity of BRCA1, while variants Q1409L, S1473P, E1586G and R1589H behave like wild-type BRCA1. In conclusion, our results suggest that variants Y1703S, W1718L and G1770V can be classified as likely pathogenic BRCA1 mutations.
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- 2013
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25. Surface respiratory electromyography and dyspnea in acute heart failure patients
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Ramon Farré, Zorba Blázquez-Bermejo, Núria Farré, Aleix Fort, Laia Carla Belarte-Tornero, Sonia Ruiz, Jordi Rigau, Daniele Luiso, Julio Martí-Almor, and Jair A. Villanueva
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Male ,Pulmonology ,Physiology ,Electromiografia ,Respiratory System ,Social Sciences ,Pilot Projects ,Electromyography ,Insuficiència cardíaca ,Thoracic Diaphragm ,Medicine and Health Sciences ,Psychology ,Prospective Studies ,Respiratory system ,Prospective cohort study ,Diafragma (Anatomia) ,Aged, 80 and over ,Multidisciplinary ,medicine.diagnostic_test ,Respiration ,Pectoralis minor muscle ,Muscle Analysis ,Respiratory Muscles ,Diaphragm (structural system) ,Dispnea ,Bioassays and Physiological Analysis ,Breathing ,Research Design ,Acute Disease ,Cardiology ,Medicine ,Female ,Sensory Perception ,Anatomy ,Muscle Electrophysiology ,Research Article ,medicine.medical_specialty ,Science ,Diaphragm ,Heart failure ,Research and Analysis Methods ,Pectoralis Muscles ,Internal medicine ,Respiratory muscle ,medicine ,Humans ,Aged ,Heart Failure ,business.industry ,Electrophysiological Techniques ,Biology and Life Sciences ,Aparell respiratori--Malalties ,Pilot Studies ,medicine.disease ,Aturada cardíaca ,Dyspnea ,Physiological Processes ,business ,Neuroscience - Abstract
Introduction and objectives: Dyspnea is the most common symptom among hospitalized patients with heart failure (HF) but besides dyspnea questionnaires (which reflect the subjective patient sensation and are not fully validated in HF) there are no measurable physiological variables providing objective assessment of dyspnea in a setting of acute HF patients. Studies performed in respiratory patients suggest that the measurement of electromyographic (EMG) activity of the respiratory muscles with surface electrodes correlates well with dyspnea. Our aim was to test the hypothesis that respiratory muscles EMG activity is a potential marker of dyspnea severity in acute HF patients. Methods: Prospective and descriptive pilot study carried out in 25 adult patients admitted for acute HF. Measurements were carried out with a cardio-respiratory portable polygraph including EMG surface electrodes for measuring the activity of main (diaphragm) and accessory (scalene and pectoralis minor) respiratory muscles. Dyspnea sensation was assessed by means of the Likert 5 questionnaire. Data were recorded during 3 min of spontaneous breathing and after breathing at maximum effort for several cycles for normalizing data. An index to quantify the activity of each respiratory muscle was computed. This assessment was carried out within the first 24 h of admission, and at day 2 and 5. Results: Dyspnea score decreased along the three measured days. Diaphragm and scalene EMG index showed a positive and significant direct relationship with dyspnea score (p
- Published
- 2020
26. Bcl-x(L) blocks a mitochondrial inner membrane channel and prevents Ca2+ overload-mediated cell death.
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Daniel Tornero, Inmaculada Posadas, and Valentín Ceña
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Medicine ,Science - Abstract
Apoptosis is an active process that plays a key role in many physiological and pathological conditions. One of the most important organelles involved in apoptosis regulation is the mitochondrion. An increase in intracellular Ca(2+) is a general mechanism of toxicity in neurons which occurs in response to different noxious stimuli like excitotoxicity and ischemia producing apoptotic and necrotic cell death through mitochondria-dependent mechanisms. The Bcl-2 family of proteins modulate the release of pro-apoptotic factors from the mitochondrial intermembrane space during cell death induction by different stimuli. In this work, we have studied, using single-cell imaging and patch-clamp single channel recording, the mitochondrial mechanisms involved in the neuroprotective effect of Bcl-x(L) on Ca(2+) overload-mediated cell death in human neuroblastoma SH-SY5Y cells. We have found that Bcl-x(L) neuroprotective actions take place at mitochondria where this antiapoptotic protein delays both mitochondrial potential collapse and opening of the permeability transition pore by preventing Ca(2+)-mediated mitochondrial multiple conductance channel opening. Bcl-x(L) neuroprotective actions were antagonized by the Bcl-x(L) inhibitor ABT-737 and potentiated by the Ca(2+) chelator BAPTA-AM. As a consequence, this would prevent free radical production, mitochondrial membrane permeabilization, release from mitochondria of pro-apoptotic molecules, caspase activation and cellular death.
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- 2011
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27. Investigating Neolithic caprine husbandry in the Central Pyrenees: Insights from a multi-proxy study at Els Trocs cave (Bisaurri, Spain)
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Tejedor-Rodríguez, Cristina, primary, Moreno-García, Marta, additional, Tornero, Carlos, additional, Hoffmann, Alizé, additional, García-Martínez de Lagrán, Íñigo, additional, Arcusa-Magallón, Héctor, additional, Garrido-Pena, Rafael, additional, Royo-Guillén, José Ignacio, additional, Díaz-Navarro, Sonia, additional, Peña-Chocarro, Leonor, additional, Alt, Kurt. W., additional, and Rojo-Guerra, Manuel, additional
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- 2021
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28. Efficacy of Sphincter Control Training and medical device in the treatment of premature ejaculation: A multicenter randomized controlled clinical trial
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José A. Piqueras, Jose A. Picazo, Juan C. Marzo, Guillermo Tornero, Guillermo Hidalgo, Leandro Reina, and Jesús Rodríguez
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Male ,Physiology ,Social Sciences ,Anal Canal ,law.invention ,Treatment and control groups ,Randomized controlled trial ,law ,Reflexes ,Medicine and Health Sciences ,Psychology ,Multidisciplinary ,Coitus ,Software Engineering ,Middle Aged ,Exercise Therapy ,Treatment Outcome ,medicine.anatomical_structure ,Medicine ,Engineering and Technology ,Anatomy ,medicine.symptom ,Genital Anatomy ,Research Article ,Biotechnology ,Adult ,Computer and Information Sciences ,medicine.medical_specialty ,Drug Research and Development ,Medical device ,Ejaculation ,Science ,Bioengineering ,Research and Analysis Methods ,Computer Software ,Young Adult ,Complementary and Alternative Medicine ,Double-Blind Method ,Urethra ,Premature ejaculation ,medicine ,Humans ,Effective treatment ,Clinical Trials ,Premature Ejaculation ,Pharmacology ,Behavior ,Cognitive Behavioral Therapy ,business.industry ,Reproductive System ,Biology and Life Sciences ,Randomized Controlled Trials ,Masturbation ,Clinical trial ,Physical therapy ,Sphincter ,Medical Devices and Equipment ,Clinical Medicine ,Physiological Processes ,business ,Neuroscience ,Penis - Abstract
A new line of treatment for premature ejaculation (PE) based on the use of masturbation aid device in combination with behavioral techniques has emerged in recent years. We report a multicenter randomized clinical trial with a parallel group design to determine the effectiveness of an electronic device called Myhixel I© in the treatment of PE. Forty patients who met the criteria for the diagnosis of lifelong PE, were assigned to two treatment groups completed the Sphincter control training (SCT) program in eight weeks. The only difference between groups was the use of the device. The main measure was the “fold increase” (FI) of the intravaginal ejaculatory latency time (IELT). The geometric means of IELT show, at the end of the treatment at week 8, a superiority of the device group. The mean FI 4.27 (SD 2.59) at the end of treatment for the device group was clearly higher than obtained in the previous clinical trial, in which a specific medical device was not used. No side effects were observed and it required little therapeutic input and no partner involvement. The SCT program in combination with the Myhixel I© is an effective treatment for PE.
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- 2021
29. Prefiltering based on experimental paradigm for analysis of fMRI complex brain networks
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Jiménez, Salvador, primary, Rotger, Laura, additional, Aguirre, Carlos, additional, Muñoz, Alberto, additional, Granados, Sergio, additional, and Tornero, Jesús, additional
- Published
- 2020
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30. Surface respiratory electromyography and dyspnea in acute heart failure patients
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Luiso, Daniele, primary, Villanueva, Jair A., additional, Belarte-Tornero, Laia C., additional, Fort, Aleix, additional, Blázquez-Bermejo, Zorba, additional, Ruiz, Sonia, additional, Farré, Ramon, additional, Rigau, Jordi, additional, Martí-Almor, Julio, additional, and Farré, Núria, additional
- Published
- 2020
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31. Attenuation of reactive gliosis in stroke-injured mouse brain does not affect neurogenesis from grafted human iPSC-derived neural progenitors
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Naomi Uoshima, Zaal Kokaia, Daniel Tornero, Ulrika Wilhelmsson, Ruimin Ge, Olle Lindvall, Anna Stokowska, Milos Pekny, and Cecilia Laterza
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Male ,0301 basic medicine ,Macroglial Cells ,Somatic cell ,lcsh:Medicine ,Endogeny ,Vimentin ,Vascular Medicine ,Mice ,0302 clinical medicine ,Neural Stem Cells ,Animal Cells ,Medicine and Health Sciences ,Gliosis ,Induced pluripotent stem cell ,lcsh:Science ,Stroke ,Neurons ,Cerebral Ischemia ,Multidisciplinary ,biology ,Neurogenesis ,Cell Differentiation ,Animal Models ,Arteries ,Neurology ,Experimental Organism Systems ,Cellular Types ,Anatomy ,Neuronal Differentiation ,Research Article ,Cerebrovascular Diseases ,Induced Pluripotent Stem Cells ,Glial Cells ,Mouse Models ,Research and Analysis Methods ,03 medical and health sciences ,Model Organisms ,Glial Fibrillary Acidic Protein ,medicine ,Animals ,Humans ,Progenitor cell ,Ischemic Stroke ,lcsh:R ,Biology and Life Sciences ,Cell Biology ,Cerebral Arteries ,medicine.disease ,Mice, Inbred C57BL ,Transplantation ,030104 developmental biology ,Astrocytes ,Cellular Neuroscience ,Mutation ,Cardiovascular Anatomy ,biology.protein ,Blood Vessels ,lcsh:Q ,Neuroscience ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Induced pluripotent stem cells (iPSCs) or their progeny, derived from human somatic cells, can give rise to functional improvements after intracerebral transplantation in animal models of stroke. Previous studies have indicated that reactive gliosis, which is associated with stroke, inhibits neurogenesis from both endogenous and grafted neural stem/progenitor cells (NSPCs) of rodent origin. Here we have assessed whether reactive astrocytes affect the fate of human iPSC-derived NSPCs transplanted into stroke-injured brain. Mice with genetically attenuated reactive gliosis (deficient for GFAP and vimentin) were subjected to cortical stroke and cells were implanted adjacent to the ischemic lesion one week later. At 8 weeks after transplantation, immunohistochemical analysis showed that attenuated reactive gliosis did not affect neurogenesis or commitment towards glial lineage of the grafted NSPCs. Our findings, obtained in a human-to-mouse xenograft experiment, provide evidence that the reactive gliosis in stroke-injured brain does not affect the formation of new neurons from intracortically grafted human iPSC-derived NSPCs. However, for a potential clinical translation of these cells in stroke, it will be important to clarify whether the lack of effect of reactive gliosis on neurogenesis is observed also in a human-to-human experimental setting.
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- 2018
32. NPR1 paralogs of Arabidopsis and their role in salicylic acid perception
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Castelló, María José, primary, Medina-Puche, Laura, additional, Lamilla, Julián, additional, and Tornero, Pablo, additional
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- 2018
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33. Dispersal mode and spatial extent influence distance-decay patterns in pond metacommunities
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Tornero, Irene, primary, Boix, Dani, additional, Bagella, Simonetta, additional, Pinto-Cruz, Carla, additional, Caria, Maria Carmela, additional, Belo, Anabela, additional, Lumbreras, Ana, additional, Sala, Jordi, additional, Compte, Jordi, additional, and Gascón, Stéphanie, additional
- Published
- 2018
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34. Attenuation of reactive gliosis in stroke-injured mouse brain does not affect neurogenesis from grafted human iPSC-derived neural progenitors
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Laterza, Cecilia, primary, Uoshima, Naomi, additional, Tornero, Daniel, additional, Wilhelmsson, Ulrika, additional, Stokowska, Anna, additional, Ge, Ruimin, additional, Pekny, Milos, additional, Lindvall, Olle, additional, and Kokaia, Zaal, additional
- Published
- 2018
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35. Hidden α-helical propensity segments within disordered regions of the transcriptional activator CHOP
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Canales, Ángeles, primary, Rösinger, Marcel, additional, Sastre, Javier, additional, Felli, Isabella C., additional, Jiménez-Barbero, Jesús, additional, Giménez-Gallego, Guillermo, additional, and Fernández-Tornero, Carlos, additional
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- 2017
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36. β-carbonic anhydrases play a role in salicylic acid perception in Arabidopsis
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Medina-Puche, Laura, primary, Castelló, María José, additional, Canet, Juan Vicente, additional, Lamilla, Julián, additional, Colombo, María Laura, additional, and Tornero, Pablo, additional
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- 2017
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37. Genetic variation associated with cardiovascular risk in autoimmune diseases
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Perrotti, Pedro P., Aterido, Adrià, Fernández Nebro, Antonio, Cañete Crespillo, Juan D., Ferrándiz, Carlos, Tornero, Jesús, Gisbert, Javier P., Domènech, Eugeni, Fernández Gutiérrez, Benjamín, Gomollón, Fernando, Garcia Planella, Esther, Fernández, Emilia, Sanmartí, Raimon, Gratacós, Jordi, Martínez Taboada, Víctor Manuel, Rodríguez Rodríguez, Luis, Palau, Núria, Tortosa, Raül, Corbeto, Mireia L., Lasanta, María L., Marsal, Sara, Julià, Antonio, Nolla Solé, Joan Miquel, Montilla, Carlos, Ramírez, Julio, Universitat de Barcelona, and Universidad de Cantabria
- Subjects
Male ,0301 basic medicine ,lcsh:Medicine ,Autoimmunity ,Disease ,Cardiovascular Medicine ,medicine.disease_cause ,Polymorphism (computer science) ,Medicine and Health Sciences ,lcsh:Science ,education.field_of_study ,Multidisciplinary ,Malalties autoimmunitàries ,Genomics ,Cardiovascular Diseases ,Female ,Research Article ,Immunology ,Population ,Polymorphism, Single Nucleotide ,Autoimmune Diseases ,03 medical and health sciences ,Genetic variation ,Genetics ,Genome-Wide Association Studies ,medicine ,Humans ,Genetic Predisposition to Disease ,education ,Genotyping ,Autoimmune disease ,Evolutionary Biology ,Population Biology ,Malalties cardiovasculars ,business.industry ,lcsh:R ,Biology and Life Sciences ,Computational Biology ,Genetic Variation ,Human Genetics ,Genome Analysis ,medicine.disease ,030104 developmental biology ,Genetic Loci ,Genetics of Disease ,Genetic Polymorphism ,Etiology ,lcsh:Q ,Clinical Immunology ,Clinical Medicine ,business ,Genètica ,Population Genetics - Abstract
Autoimmune diseases have a higher prevalence of cardiovascular events compared to the general population. The objective of this study was to investigate the genetic basis of cardiovascular disease (CVD) risk in autoimmunity. We analyzed genome-wide genotyping data from 6,485 patients from six autoimmune diseases that are associated with a high socioeconomic impact. First, for each disease, we tested the association of established CVD risk loci. Second, we analyzed the association of autoimmune disease susceptibility loci with CVD. Finally, to identify genetic patterns associated with CVD risk, we applied the cross-phenotype meta-analysis approach (CPMA) on the genome-wide data. A total of 17 established CVD risk loci were significantly associated with CVD in the autoimmune patient cohorts. From these, four loci were found to have significantly different genetic effects across autoimmune diseases. Six autoimmune susceptibility loci were also found to be associated with CVD risk. Genome-wide CPMA analysis identified 10 genetic clusters strongly associated with CVD risk across all autoimmune diseases. Two of these clusters are highly enriched in pathways previously associated with autoimmune disease etiology (TNF alpha and IFN gamma cytokine pathways). The results of this study support the presence of specific genetic variation associated with the increase of CVD risk observed in autoimmunity.
- Published
- 2017
38. Equality in Educational Policy and the Heritability of Educational Attainment
- Author
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Colodro-Conde, Lucía, primary, Rijsdijk, Frühling, additional, Tornero-Gómez, María J., additional, Sánchez-Romera, Juan F., additional, and Ordoñana, Juan R., additional
- Published
- 2015
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39. Altered Expression of Wnt Signaling Pathway Components in Osteogenesis of Mesenchymal Stem Cells in Osteoarthritis Patients
- Author
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Tornero-Esteban, Pilar, primary, Peralta-Sastre, Ascensión, additional, Herranz, Eva, additional, Rodríguez-Rodríguez, Luis, additional, Mucientes, Arkaitz, additional, Abásolo, Lydia, additional, Marco, Fernando, additional, Fernández-Gutiérrez, Benjamín, additional, and Lamas, José Ramón, additional
- Published
- 2015
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40. Variation at FCGR2A and Functionally Related Genes Is Associated with the Response to Anti-TNF Therapy in Rheumatoid Arthritis
- Author
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Avila-Pedretti, Gabriela, primary, Tornero, Jesús, additional, Fernández-Nebro, Antonio, additional, Blanco, Francisco, additional, González-Alvaro, Isidoro, additional, Cañete, Juan D., additional, Maymó, Joan, additional, Alperiz, Mercedes, additional, Fernández-Gutiérrez, Benjamín, additional, Olivé, Alex, additional, Corominas, Héctor, additional, Erra, Alba, additional, Aterido, Adrià, additional, López Lasanta, María, additional, Tortosa, Raül, additional, Julià, Antonio, additional, and Marsal, Sara, additional
- Published
- 2015
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41. Functional and Structural Analysis of C-Terminal BRCA1 Missense Variants
- Author
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Quiles, Francisco, primary, Fernández-Rodríguez, Juana, additional, Mosca, Roberto, additional, Feliubadaló, Lídia, additional, Tornero, Eva, additional, Brunet, Joan, additional, Blanco, Ignacio, additional, Capellá, Gabriel, additional, Pujana, Miquel Àngel, additional, Aloy, Patrick, additional, Monteiro, Alvaro, additional, and Lázaro, Conxi, additional
- Published
- 2013
- Full Text
- View/download PDF
42. An Allele of Arabidopsis COI1 with Hypo- and Hypermorphic Phenotypes in Plant Growth, Defence and Fertility
- Author
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Dobón, Albor, primary, Wulff, Brande B. H., additional, Canet, Juan Vicente, additional, Fort, Patrocinio, additional, and Tornero, Pablo, additional
- Published
- 2013
- Full Text
- View/download PDF
43. Bcl-xL Blocks a Mitochondrial Inner Membrane Channel and Prevents Ca2+ Overload-Mediated Cell Death
- Author
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Tornero, Daniel, primary, Posadas, Inmaculada, additional, and Ceña, Valentín, additional
- Published
- 2011
- Full Text
- View/download PDF
44. Bcl-xL Blocks a Mitochondrial Inner Membrane Channel and Prevents Ca2+ Overload-Mediated Cell Death
- Author
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Valentín Ceña, Inmaculada Posadas, and Daniel Tornero
- Subjects
Patch-Clamp Techniques ,Mitochondrial intermembrane space ,Excitotoxicity ,lcsh:Medicine ,Apoptosis ,Mitochondrion ,medicine.disease_cause ,Mitochondrial apoptosis-induced channel ,Ion Channels ,Piperazines ,Nitrophenols ,Molecular Cell Biology ,Neurobiology of Disease and Regeneration ,lcsh:Science ,Inner mitochondrial membrane ,Egtazic Acid ,Apoptotic Signaling Cascade ,Membrane Potential, Mitochondrial ,Sulfonamides ,Multidisciplinary ,Cell Death ,Ionomycin ,Mechanisms of Signal Transduction ,Neurodegenerative Diseases ,Parkinson Disease ,Signaling Cascades ,Mitochondria ,Cell biology ,Neurology ,Caspases ,Mitochondrial Membranes ,Medicine ,Single-Cell Analysis ,Ion Channel Gating ,Research Article ,Signal Transduction ,Programmed cell death ,bcl-X Protein ,Biology ,Signaling Pathways ,Permeability ,Cell Line, Tumor ,Calcium-Mediated Signal Transduction ,medicine ,Humans ,lcsh:R ,Biphenyl Compounds ,Biological Transport ,Gene Expression Regulation ,Mitochondrial permeability transition pore ,Calcium Signaling Cascade ,Cellular Neuroscience ,DNAJA3 ,lcsh:Q ,Calcium ,Molecular Neuroscience ,Neuroscience - Abstract
Apoptosis is an active process that plays a key role in many physiological and pathological conditions. One of the most important organelles involved in apoptosis regulation is the mitochondrion. An increase in intracellular Ca(2+) is a general mechanism of toxicity in neurons which occurs in response to different noxious stimuli like excitotoxicity and ischemia producing apoptotic and necrotic cell death through mitochondria-dependent mechanisms. The Bcl-2 family of proteins modulate the release of pro-apoptotic factors from the mitochondrial intermembrane space during cell death induction by different stimuli. In this work, we have studied, using single-cell imaging and patch-clamp single channel recording, the mitochondrial mechanisms involved in the neuroprotective effect of Bcl-x(L) on Ca(2+) overload-mediated cell death in human neuroblastoma SH-SY5Y cells. We have found that Bcl-x(L) neuroprotective actions take place at mitochondria where this antiapoptotic protein delays both mitochondrial potential collapse and opening of the permeability transition pore by preventing Ca(2+)-mediated mitochondrial multiple conductance channel opening. Bcl-x(L) neuroprotective actions were antagonized by the Bcl-x(L) inhibitor ABT-737 and potentiated by the Ca(2+) chelator BAPTA-AM. As a consequence, this would prevent free radical production, mitochondrial membrane permeabilization, release from mitochondria of pro-apoptotic molecules, caspase activation and cellular death.
- Published
- 2011
45. Bcl-xL Blocks a Mitochondrial Inner Membrane Channel and Prevents Ca2+ Overload-Mediated Cell Death.
- Author
-
Tornero, Daniel, Posadas, Inmaculada, and Ceñ a, Valentín
- Subjects
- *
MITOCHONDRIA , *CALCIUM channels , *CELL death , *APOPTOSIS , *ORGANELLES , *NEURAL stimulation , *CHRONIC lymphocytic leukemia , *NEUROPROTECTIVE agents - Abstract
Apoptosis is an active process that plays a key role in many physiological and pathological conditions. One of the most important organelles involved in apoptosis regulation is the mitochondrion. An increase in intracellular Ca2+ is a general mechanism of toxicity in neurons which occurs in response to different noxious stimuli like excitotoxicity and ischemia producing apoptotic and necrotic cell death through mitochondria-dependent mechanisms. The Bcl-2 family of proteins modulate the release of pro-apoptotic factors from the mitochondrial intermembrane space during cell death induction by different stimuli. In this work, we have studied, using single-cell imaging and patch-clamp single channel recording, the mitochondrial mechanisms involved in the neuroprotective effect of Bcl-xL on Ca2+overload-mediated cell death in human neuroblastoma SH-SY5Y cells. We have found that Bcl-xL neuroprotective actions take place at mitochondria where this antiapoptotic protein delays both mitochondrial potential collapse and opening of the permeability transition pore by preventing Ca2+-mediated mitochondrial multiple conductance channel opening. Bcl-xL neuroprotective actions were antagonized by the Bcl-xL inhibitor ABT-737 and potentiated by the Ca2+ chelator BAPTA-AM. As a consequence, this would prevent free radical production, mitochondrial membrane permeabilization, release from mitochondria of pro-apoptotic molecules, caspase activation and cellular death. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
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