Manuel Palacı́n, Raúl Estévez, Joan Bertran, António Zorzano,
Palacı́n, Manuel, Raúl Estévez, Joan Bertran, and Antonio Zorzano. Molecular Biology of Mammalian Plasma Membrane Amino Acid Transporters. Physiol. Rev. 78: 969– ...
Tópico(s): Pancreatic function and diabetes
1998 - American Physiological Society | Physiological Reviews
Juan Del Coso, Emma Estévez, Raúl Antonio Baquero, Ricardo Mora‐Rodríguez,
The effects that rehydrating drinks ingested during exercise may have on anaerobic exercise performance are unclear. This study aimed to determine which of four commercial rehydrating drinks better maintains leg power and force during prolonged cycling in the heat. Seven endurance-trained and heat-acclimatized cyclists pedaled for 120 min at 63% maximum oxygen consumption in a hot, dry environment (36 °C; 29% humidity, 1.9 m·s –1 airflow). In five randomized trials, during exercise, subjects drank ...
Tópico(s): Exercise and Physiological Responses
2008 - NRC Research Press | Applied Physiology Nutrition and Metabolism
Eduardo Collantes‐Estévez, Raúl Veroz, Alejandro Escudero‐Contreras, Elisa Muñoz, Maria Carmen Muñoz, Agustín Fernández Cisnal, Veronica Perez,
When evaluating patients for spondyloarthropathy, clinicians use the 'possible spondyloarthropathy' category to indicate that they are unsure about the diagnosis. We sought to determine whether Amor's criteria or the European Spondyloarthropathy Study Group (ESSG) criteria could lift thi uncertainty.During a Spanish study designed to validate criteria for spondyloar thropathies, 102 patients were classified in the 'possible spondyloarthropathy' category. We divided these patients into subgroups based ...
Tópico(s): Rheumatoid Arthritis Research and Therapies
2000 - Elsevier BV | Joint Bone Spine
Susana Soares, Ignacio García‐Estévez, Raúl Ferrer‐Gallego, Natércia F. Brás, Elsa Brandão, Mafalda Silva, Natércia Teixeira, Fátima Fonseca, Sérgio F. Sousa, Frederico Ferreira‐da‐Silva, Nuno Mateus, Víctor de Freitas,
In this work, saturation transfer difference-NMR, isothermal microcalorimetry and molecular dynamics simulations have been used to study the individual interactions between basic, glycosylated and acidic proline-rich proteins (bPRPS, gPRPs, aPRPs) and P-B peptide with some representative food tannins [procyanidin B2, procyanidin B2 3′-O-gallate (B2g) and procyanidin trimer (catechin-4–8-catechin-4–8-catechin)]. Results showed that P-B peptide was in general the salivary protein (SP) with higher affinity ...
Tópico(s): Muscle metabolism and nutrition
2017 - Elsevier BV | Food Chemistry
Javier Ampuero, R. Aller, Rocío Gallego‐Durán, Jesús M. Bañales, Javier Crespo, Carmelo García‐Monzón, María Jesús Pareja, Eduardo Vilar‐Gómez, Juan Caballería, Desamparados Escudero‐García, Judith Gómez‐Camarero, José Luís Calleja, Mercedes Alfaro Latorre, Agustı́n Albillos, Javier Salmerón, Patricia Aspichueta, Oreste Lo Iacono, Rubén Francés, Salvador Benlloch, Conrado Fernández‐Rodríguez, Javier García‐Samaniego, Pamela Estévez, Raúl J. Andrade, Juan Turnés, Manuel Romero‐Gómez,
Summary Background Metabolically healthy obesity ( MHO ) shows a reduced risk compared with obese patients with adverse metabolic conditions. Lean people suffering some metabolic derangements also have non‐alcoholic fatty liver disease ( NAFLD )‐related outcomes compared with non‐obese subjects with a few metabolic risks. Aim To define the impact of the metabolic status on the NAFLD ‐related outcomes, beyond the presence of obesity. Methods We designed a multicentre cross‐sectional study, including 1058 ...
Tópico(s): Pancreatitis Pathology and Treatment
2018 - Wiley | Alimentary Pharmacology & Therapeutics
Javier Ampuero, Raluca Pais, R. Aller, Rocío Gallego‐Durán, Javier Crespo, Carmelo García‐Monzón, Jérôme Boursier, Eduardo Vilar, Salvatore Petta, Ming‐Hua Zheng, Desamparados Escudero, José Luís Calleja, Patricia Aspichueta, M. Diago, José Miguel Rosales Zábal, Joan Caballería, Judith Gómez‐Camarero, Oreste Lo Iacono, Salvador Benlloch, Agustı́n Albillos, Juan Turnés, Jesús M. Bañales, Vlad Ratziu, Manuel Romero‐Gómez, Salvador Agustin, Francisco Jorquera, Rubén Francés, Javier García‐Samaniego, Javier Salmerón, Conrado Fernández-Rodrı́guez, Pamela Estévez, Raúl J. Andrade, Germán Soriano, Miguel Fernández‐Bermejo, M. Arias, Rebeca Sigüenza, Aurora Giannetti, E Maroto,
Background & AimsFibrosis affects prognoses for patients with nonalcoholic fatty liver disease (NAFLD). Several non-invasive scoring systems have aimed to identify patients at risk for advanced fibrosis, but inconclusive results and variations in features of patients (diabetes, obesity and older age) reduce their diagnostic accuracy. We sought to develop a scoring system based on serum markers to identify patients with NAFLD at risk for advanced fibrosis.MethodsWe collected data from 2452 patients with ...
Tópico(s): Hepatitis C virus research
2019 - Elsevier BV | Clinical Gastroenterology and Hepatology
... of Mammalian Plasma Membrane Amino Acid TransportersMANUEL PALACÍN, RAÚL ESTÉVEZ, JOAN BERTRAN, and ANTONIO ZORZANO1 October 1998 | Physiological ...
Tópico(s): Infant Nutrition and Health
1982 - American Physiological Society | Physiological Reviews
... of Mammalian Plasma Membrane Amino Acid TransportersMANUEL PALACÍN, RAÚL ESTÉVEZ, JOAN BERTRAN, and ANTONIO ZORZANO1 October 1998 | Physiological ...
Tópico(s): Phytase and its Applications
1990 - American Physiological Society | Physiological Reviews
... of Mammalian Plasma Membrane Amino Acid TransportersMANUEL PALACÍN, RAÚL ESTÉVEZ, JOAN BERTRAN, and ANTONIO ZORZANO1 October 1998 | Physiological ...
Tópico(s): Sulfur Compounds in Biology
1988 - American Physiological Society | Physiological Reviews
Oona Scotti, Amos Nur, Raul Estevez,
The focus of this paper is to understand distributed deformation, in particular the relationship between fault slip and rotation of faults and blocks in a three dimensional stress field. Regions of distributed deformation, such as Southern California, are organized in complex arrays of contemporaneously active block‐faulted domains. We believe that the present day orientation of faults in many domains is due to the contemporaneous slip and rotation of the faults and of the blocks they bound. Traditional ...
Tópico(s): High-pressure geophysics and materials
1991 - American Geophysical Union | Journal of Geophysical Research Atmospheres
Raúl Estévez, Thomas J. Jentsch,
CLC chloride channels form a large gene family that is found in bacteria, archae and eukaryotes. Previous mutagenesis studies on CLC chloride channels, combined with electrophysiology, strongly supported the theory that these channels form a homodimeric structure with one pore per subunit (a'double-barrelled' channel), and also provided clues about gating and permeation. Recently, the crystal structures of two bacterial CLC proteins have been obtained by X-ray diffraction analysis. They confirm the ...
Tópico(s): Nicotinic Acetylcholine Receptors Study
2002 - Elsevier BV | Current Opinion in Structural Biology
Raúl Estévez, Björn C. Schroeder, Alessio Accardi, Thomas J. Jentsch, Michael Pusch,
Crystal structures of bacterial CLC proteins were solved recently, but it is unclear to which level of detail they can be extrapolated to mammalian chloride channels. Exploiting the difference in inhibition by 9-anthracene carboxylic acid (9-AC) between ClC-0, -1, and -2, we identified a serine between helices O and P as crucial for 9-AC binding. Mutagenesis based on the crystal structure identified further residues affecting inhibitor binding. They surround a partially hydrophobic pocket close to ...
Tópico(s): Neuroscience and Neuropharmacology Research
2003 - Cell Press | Neuron
Anna Duarri, Óscar Teijido, Tania López-Hernández, Gert C. Scheper, H. Barrière, Ilja Boor, Fernando Aguado, António Zorzano, Manuel Palacı́n, Albert Martı́nez, Gergely L. Lukács, Marjo S. van der Knaap, Virginia Nunes, Raúl Estévez,
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare type of leukodystrophy, most often caused by mutations in the MLC1 gene. MLC1 is an oligomeric plasma membrane (PM) protein of unknown function expressed mainly in glial cells and neurons. Most disease-causing missense mutations dramatically reduced the total and PM MLC1 expression levels in Xenopus oocytes and mammalian cells. The impaired expression of the mutants was verified in primary cultures of rat astrocytes, as well ...
Tópico(s): Electrochemical Analysis and Applications
2008 - Oxford University Press | Human Molecular Genetics
Ilja Boor, Machiel Nagtegaal, Wouter Kamphorst, Paul van der Valk, Jan C. Pronk, Jack van Horssen, Argirios Dinopoulos, Kevin E. Bove, I Pascual-Castroviejo, Francesco Muntoni, Raúl Estévez, Gert C. Scheper, Marjo S. van der Knaap,
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a progressive cerebral white matter disease with onset in childhood, caused by mutations in the MLC1 gene. MLC1 is a protein with unknown function that is mainly expressed in the brain in astrocytic endfeet at the blood–brain and cerebrospinal fluid–brain barriers. It shares its localization at astrocytic endfeet with the dystrophin-associated glycoprotein complex (DGC). The objective of the present study was to investigate the possible ...
Tópico(s): Mitochondrial Function and Pathology
2007 - Springer Science+Business Media | Acta Neuropathologica
Óscar Teijido, Ricardo P. Casaroli‐Marano, Tatjana Kharkovets, Fernando Aguado, António Zorzano, Manuel Palacı́n, Eduardo Soriano, Albert Martı́nez, Raúl Estévez,
Mutations in MLC1 cause megalencephalic leukoencephalopathy with subcortical cysts (MLC), a disorder characterized clinically by macrocephaly, deterioration of motor functions, epilepsy and mental decline. Recent studies have detected MLC1 mRNA and protein in astroglial processes. In addition, our group previously reported MLC1 expression in some neurons in the adult mouse brain. Here we performed an exhaustive study of the expression pattern of MLC1 in the developing mouse brain by means of optic ...
Tópico(s): MicroRNA in disease regulation
2007 - Elsevier BV | Neurobiology of Disease
María J. Macías, Óscar Teijido, Giovanni Zifarelli, Pau Martin, Ximena Ramirez‐Espain, António Zorzano, Manuel Palacı́n, Michael Pusch, Raúl Estévez,
Myotonia is a state of hyperexcitability of skeletal-muscle fibres. Mutations in the ClC-1 Cl− channel cause recessive and dominant forms of this disease. Mutations have been described throughout the protein-coding region, including three sequence variations (A885P, R894X and P932L) in a distal C-terminal stretch of residues [CTD (C-terminal domain) region] that are not conserved between CLC proteins. We show that surface expression of these mutants is reduced in Xenopus oocytes compared with wild- ...
Tópico(s): Cardiomyopathy and Myosin Studies
2007 - Portland Press | Biochemical Journal
Margreet C. Ridder, Ilja Boor, Johannes C. Lodder, Nienke L. Postma, Xavier Capdevila‐Nortes, Anna Duarri, Arjen B. Brussaard, Raúl Estévez, Gert C. Scheper, Huibert D. Mansvelder, Marjo S. van der Knaap,
Megalencephalic leucoencephalopathy with subcortical cysts is a genetic brain disorder with onset in early childhood. Affected infants develop macrocephaly within the first year of life, after several years followed by slowly progressive, incapacitating cerebellar ataxia and spasticity. From early on, magnetic resonance imaging shows diffuse signal abnormality and swelling of the cerebral white matter, with evidence of highly increased white matter water content. In most patients, the disease is ...
Tópico(s): Mitochondrial Function and Pathology
2011 - Oxford University Press | Brain
Tania López-Hernández, Sònia Sirisi, Xavier Capdevila‐Nortes, Marisol Montolio, Víctor Fernández‐Dueñas, Gert C. Scheper, Marjo S. van der Knaap, Pilar Casquero, Francisco Ciruela, Isidró Ferrer, Virginia Nunes, Raúl Estévez,
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare leukodystrophy caused by mutations in MLC1 or GLIALCAM. The GLIALCAM gene product functions as an MLC1 beta-subunit. We aim to further clarify the molecular mechanisms of MLC caused by mutations in MLC1 or GLIALCAM. For this purpose, we analyzed a human post-mortem brain obtained from an MLC patient, who was homozygous for a missense mutation (S69L) in MLC1. We showed that this mutation affects the stability of MLC1 in vitro ...
Tópico(s): RNA Research and Splicing
2011 - Oxford University Press | Human Molecular Genetics
Tania López-Hernández, Margreet C. Ridder, Marisol Montolio, Xavier Capdevila‐Nortes, Emiel Polder, Sònia Sirisi, Anna Duarri, Uwe Schulte, Bernd Fakler, Virginia Nunes, Gert C. Scheper, Albert Martı́nez, Raúl Estévez, Marjo S. van der Knaap,
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a leukodystrophy characterized by early-onset macrocephaly and delayed-onset neurological deterioration. Recessive MLC1 mutations are observed in 75% of patients with MLC. Genetic-linkage studies failed to identify another gene. We recently showed that some patients without MLC1 mutations display the classical phenotype; others improve or become normal but retain macrocephaly. To find another MLC-related gene, we used quantitative ...
Tópico(s): RNA Interference and Gene Delivery
2011 - Elsevier BV | The American Journal of Human Genetics
Anna Duarri, Miguel López de Heredia, Xavier Capdevila‐Nortes, Margreet C. Ridder, Marisol Montolio, Tania López-Hernández, Ilja Boor, Chun‐Fu Lien, Tracy L. Hagemann, Albee Messing, Dariusz C. Górecki, Gert C. Scheper, Albert Martı́nez, Virginia Nunes, Marjo S. van der Knaap, Raúl Estévez,
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare type of leukodystrophy, in the majority of cases caused by mutations in the MLC1 gene. MRI from MLC patients shows diffuse cerebral white matter signal abnormality and swelling, with evidence of increased water content. Histopathology in a MLC patient shows vacuolation of myelin, which causes the cerebral white matter swelling. MLC1 protein is expressed in astrocytic processes that are part of blood- and cerebrospinal fluid- ...
Tópico(s): Electrochemical Analysis and Applications
2011 - Elsevier BV | Neurobiology of Disease
Giorgia Montagna, Óscar Teijido, Eléonore Eymard‐Pierre, Koutarou Muraki, Bruce H. Cohen, Annalivia Loizzo, Pietro Grosso, Gioacchino Tedeschi, Manuel Palacı́n, Odile Boespflug‐Tanguy, Enrico Bertini, Filippo M. Santorelli, Raúl Estévez,
Nine new unrelated patients presenting vacuolating myelinopathy with subcortical cysts were identified and analyzed for variations in the MLC1 gene. We detected 12 mutations (p.Leu37fs, p.Met80Val, p.Leu83Phe, p.Pro92Ser, p.Ser93Leu, p.Ile108fs, p.Gly130Arg, p.Cys171fs, p.Glu202Lys, p.Ser269Tyr, p.Ala275Asn, and p.Leu310_311insLeu) of which nine were novel. In one patient we did not detect mutations. Using a heterologous system, three new missense variants (p.Glu202Lys, p.Ser269Tyr, and p.Ala275Asn) ...
Tópico(s): Alzheimer's disease research and treatments
2006 - Wiley | Human Mutation
Marjo S. van der Knaap, Ilja Boor, Raúl Estévez,
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is characterised by chronic white matter oedema. The disease has an infantile onset and leads to slow neurological deterioration in most cases, but, surprisingly, some patients recover. The first disease gene, MLC1, identified in 2001, is mutated in 75% of patients. At that time, nothing was known about MLC1 protein function and the pathophysiology of MLC. More recently, HEPACAM (also called GLIALCAM) has been identified as a second ...
Tópico(s): Retinal Development and Disorders
2012 - Elsevier BV | The Lancet Neurology
Elena Jeworutzki, Tania López-Hernández, Xavier Capdevila‐Nortes, Sònia Sirisi, Luiza Bengtsson, Marisol Montolio, Giovanni Zifarelli, Tanit Arnedo, Catrin Swantje Müller, Uwe Schulte, Virginia Nunes, Albert Martı́nez, Thomas J. Jentsch, Xavier Gasull, Michael Pusch, Raúl Estévez,
Ion fluxes mediated by glial cells are required for several physiological processes such as fluid homeostasis or the maintenance of low extracellular potassium during high neuronal activity. In mice, the disruption of the Cl(-) channel ClC-2 causes fluid accumulation leading to myelin vacuolation. A similar vacuolation phenotype is detected in humans affected with megalencephalic leukoencephalopathy with subcortical cysts (MLC), a leukodystrophy which is caused by mutations in MLC1 or GLIALCAM. We ...
Tópico(s): Mitochondrial Function and Pathology
2012 - Cell Press | Neuron
Susanna Bodoy, Lorena Martín‐Jaular, António Zorzano, Manuel Palacı́n, Raúl Estévez, Joan Bertran,
System L amino acid transporters mediate the movement of bulky neutral amino acids across cell membranes. Until now three proteins that induce system L activity have been identified: LAT1, LAT2, and LAT3. The former two proteins belong to the solute carrier family 7 (SLC7), whereas the latter belongs to SLC43. In the present study we present a new cDNA, designated LAT4, which also mediates system L activity when expressed in Xenopus laevis oocytes. Human LAT4 exhibits 57% identity to human LAT3. ...
Tópico(s): Metabolism and Genetic Disorders
2005 - Elsevier BV | Journal of Biological Chemistry
Juan J. Chillarón, Raúl Estévez, Conchi Mora, Carsten A. Wagner, H. Suessbrich, Florian Läng, Josep Lluis Gelpí, Xavier Testar, Andreas Büsch, António Zorzano, Manuel Palacı́n,
Mutations in the rBAT gene cause type I cystinuria, a common inherited aminoaciduria of cystine and dibasic amino acids due to their defective renal and intestinal reabsorption (Calonge, M. J., Gasparini, P., Chillarón, J., Chillón, M., Gallucci, M., Rousaud, F., Zelante, L., Testar, X., Dallapiccola, B., Di Silverio, F., Barceló, P., Estivill, X., Zorzano, A., Nunes, V., and Palacín, M. (1994) Nat. Genet. 6, 420-426; Calonge, M. J., Volipini, V., Bisceglia, L., Rousaud, F., De Sanctis, L., Beccia, ...
Tópico(s): Mass Spectrometry Techniques and Applications
1996 - Elsevier BV | Journal of Biological Chemistry
Raúl Estévez, Michael Pusch, Carles Ferrer‐Costa, Modesto Orozco, Thomas J. Jentsch,
All eukaryotic CLC Cl(-) channel subunits possess a long cytoplasmic carboxy-terminus that contains two so-called CBS (cystathionine beta-synthase) domains. These domains are found in various unrelated proteins from all phylae. The crystal structure of the CBS domains of inosine monophosphate dehydrogenase (IMPDH) is known, but it is not known whether this structure is conserved in CLC channels. Working primarily with ClC-1, we used deletion scanning mutagenesis, coimmunoprecipitation and electrophysiology ...
Tópico(s): Adenosine and Purinergic Signaling
2004 - Wiley | The Journal of Physiology
Óscar Teijido, Albert Martı́nez, Michael Pusch, António Zorzano, Eduardo Soriano, José Antonio del Rı́o, Manuel Palacı́n, Raúl Estévez,
Mutations in the MLC1 gene are responsible for one form of the neurological disorder megalencephalic leukoencephalopathy with subcortical cysts (MLC). The disease is a type of vacuolating myelinopathy. The biochemical properties and the function of the MLC1 protein are unknown. To characterize MLC1, we generated polyclonal antibodies. The MLC1 protein was detected in the brain, assembled into higher molecular complexes, as assessed by assembly-dependent trafficking assays. In situ hybridization and ...
Tópico(s): Neuroscience and Neuropharmacology Research
2004 - Oxford University Press | Human Molecular Genetics
Manuel Palacı́n, Joan Bertran, Juan J. Chillarón, Raúl Estévez, António Zorzano,
Heteromeric amino acid transporters (HATs) are composed of two subunits, a polytopic membrane protein (the light subunit) and a disulfide-linked type II membrane glycoprotein (the heavy subunit). HATs represent several of the classic mammalian amino acid transport systems (e.g., L isoforms, y+L isoforms, asc, xc−, and b0,+). The light subunits confer the amino acid transport specificity to the HAT. Two transporters of this family are relevant for inherited aminoacidurias. Mutations in any of the two ...
Tópico(s): Biomedical Research and Pathophysiology
2004 - Elsevier BV | Molecular Genetics and Metabolism
Elena Jeworutzki, Laura Lagostena, Xabier Elorza‐Vidal, Tania López-Hernández, Raúl Estévez, Michael Pusch,
GlialCAM, a glial cell adhesion molecule mutated in megalencephalic leukoencephalopathy with subcortical cysts, targets the CLC-2 Cl- channel to cell contacts in glia and activates CLC-2 currents in vitro and in vivo. We found that GlialCAM clusters all CLC channels at cell contacts in vitro and thus studied GlialCAM interaction with CLC channels to investigate the mechanism of functional activation. GlialCAM slowed deactivation kinetics of CLC-Ka/barttin channels and increased CLC-0 currents opening ...
Tópico(s): Neuroscience and Neuropharmacology Research
2014 - Elsevier BV | Biophysical Journal
Maja B. Hoegg-Beiler, Sònia Sirisi, Ian J. Orozco, Isidró Ferrer, Svea Hohensee, Muriel Auberson, Kathrin Gödde, Clara Vilches, Miguel López de Heredia, Virginia Nunes, Raúl Estévez, Thomas J. Jentsch,
Defects in the astrocytic membrane protein MLC1, the adhesion molecule GlialCAM or the chloride channel ClC-2 underlie human leukoencephalopathies. Whereas GlialCAM binds ClC-2 and MLC1, and modifies ClC-2 currents in vitro, no functional connections between MLC1 and ClC-2 are known. Here we investigate this by generating loss-of-function Glialcam and Mlc1 mouse models manifesting myelin vacuolization. We find that ClC-2 is unnecessary for MLC1 and GlialCAM localization in brain, whereas GlialCAM ...
Tópico(s): Neuroinflammation and Neurodegeneration Mechanisms
2014 - Nature Portfolio | Nature Communications