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1دورية أكاديمية
المؤلفون: Katherine Johnson, Marta Bertoli, Lauren Phillips, Ana Töpf, Peter Van den Bergh, John Vissing, Nanna Witting, Shahriar Nafissi, Shirin Jamal-Omidi, Anna Łusakowska, Anna Kostera-Pruszczyk, Anna Potulska-Chromik, Nicolas Deconinck, Carina Wallgren-Pettersson, Sonja Strang-Karlsson, Jaume Colomer, Kristl G. Claeys, Willem De Ridder, Jonathan Baets, Maja von der Hagen, Roberto Fernández-Torrón, Miren Zulaica Ijurco, Juan Bautista Espinal Valencia, Andreas Hahn, Hacer Durmus, Tracey Willis, Liwen Xu, Elise Valkanas, Thomas E. Mullen, Monkol Lek, Daniel G. MacArthur, Volker Straub
المصدر: Skeletal Muscle, Vol 8, Iss 1, Pp 1-12 (2018)
مصطلحات موضوعية: Whole-exome sequencing, Dystroglycanopathies, Limb-girdle muscle weakness, Diseases of the musculoskeletal system, RC925-935
الوصف: Abstract Background Dystroglycanopathies are a clinically and genetically heterogeneous group of disorders that are typically characterised by limb-girdle muscle weakness. Mutations in 18 different genes have been associated with dystroglycanopathies, the encoded proteins of which typically modulate the binding of α-dystroglycan to extracellular matrix ligands by altering its glycosylation. This results in a disruption of the structural integrity of the myocyte, ultimately leading to muscle degeneration. Methods Deep phenotypic information was gathered using the PhenoTips online software for 1001 patients with unexplained limb-girdle muscle weakness from 43 different centres across 21 European and Middle Eastern countries. Whole-exome sequencing with at least 250 ng DNA was completed using an Illumina exome capture and a 38 Mb baited target. Genes known to be associated with dystroglycanopathies were analysed for disease-causing variants. Results Suspected pathogenic variants were detected in DPM3, ISPD, POMT1 and FKTN in one patient each, in POMK in two patients, in GMPPB in three patients, in FKRP in eight patients and in POMT2 in ten patients. This indicated a frequency of 2.7% for the disease group within the cohort of 1001 patients with unexplained limb-girdle muscle weakness. The phenotypes of the 27 patients were highly variable, yet with a fundamental presentation of proximal muscle weakness and elevated serum creatine kinase. Conclusions Overall, we have identified 27 patients with suspected pathogenic variants in dystroglycanopathy-associated genes. We present evidence for the genetic and phenotypic diversity of the dystroglycanopathies as a disease group, while also highlighting the advantage of incorporating next-generation sequencing into the diagnostic pathway of rare diseases.
وصف الملف: electronic resource
العلاقة: http://link.springer.com/article/10.1186/s13395-018-0170-1Test; https://doaj.org/toc/2044-5040Test
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2دورية أكاديمية
المؤلفون: Raquel Montero, Delia Yubero, Joan Villarroya, Desiree Henares, Cristina Jou, Maria Angeles Rodríguez, Federico Ramos, Andrés Nascimento, Carlos Ignacio Ortez, Jaume Campistol, Belen Perez-Dueñas, Mar O'Callaghan, Mercedes Pineda, Angeles Garcia-Cazorla, Jaume Colomer Oferil, Julio Montoya, Eduardo Ruiz-Pesini, Sonia Emperador, Marija Meznaric, Laura Campderros, Susana G Kalko, Francesc Villarroya, Rafael Artuch, Cecilia Jimenez-Mallebrera
المصدر: PLoS ONE, Vol 11, Iss 2, p e0148709 (2016)
الوصف: BACKGROUND:We previously described increased levels of growth and differentiation factor 15 (GDF-15) in skeletal muscle and serum of patients with mitochondrial diseases. Here we evaluated GDF-15 as a biomarker for mitochondrial diseases affecting children and compared it to fibroblast-growth factor 21 (FGF-21). To investigate the mechanism of GDF-15 induction in these pathologies we measured its expression and secretion in response to mitochondrial dysfunction. METHODS:We analysed 59 serum samples from 48 children with mitochondrial disease, 19 samples from children with other neuromuscular diseases and 33 samples from aged-matched healthy children. GDF-15 and FGF-21 circulating levels were determined by ELISA. RESULTS:Our results showed that in children with mitochondrial diseases GDF-15 levels were on average increased by 11-fold (mean 4046pg/ml, 1492 SEM) relative to healthy (350, 21) and myopathic (350, 32) controls. The area under the curve for the receiver-operating-characteristic curve for GDF-15 was 0.82 indicating that it has a good discriminatory power. The overall sensitivity and specificity of GDF-15 for a cut-off value of 550pg/mL was 67.8% (54.4%-79.4%) and 92.3% (81.5%-97.9%), respectively. We found that elevated levels of GDF-15 and or FGF-21 correctly identified a larger proportion of patients than elevated levels of GDF-15 or FGF-21 alone. GDF-15, as well as FGF-21, mRNA expression and protein secretion, were significantly induced after treatment of myotubes with oligomycin and that levels of expression of both factors significantly correlated. CONCLUSIONS:Our data indicate that GDF-15 is a valuable serum quantitative biomarker for the diagnosis of mitochondrial diseases in children and that measurement of both GDF-15 and FGF-21 improves the disease detection ability of either factor separately. Finally, we demonstrate for the first time that GDF-15 is produced by skeletal muscle cells in response to mitochondrial dysfunction and that its levels correlate in vitro with FGF-21 levels.
وصف الملف: electronic resource
العلاقة: http://europepmc.org/articles/PMC4750949?pdf=renderTest; https://doaj.org/toc/1932-6203Test
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3دورية أكاديمية
المؤلفون: Sonia Paco, Susana G Kalko, Cristina Jou, María A Rodríguez, Joan Corbera, Francesco Muntoni, Lucy Feng, Eloy Rivas, Ferran Torner, Francesca Gualandi, Anna M Gomez-Foix, Anna Ferrer, Carlos Ortez, Andrés Nascimento, Jaume Colomer, Cecilia Jimenez-Mallebrera
المصدر: PLoS ONE, Vol 10, Iss 5, p e0128614 (2015)
وصف الملف: electronic resource
العلاقة: http://europepmc.org/articles/PMC4431837?pdf=renderTest; https://doaj.org/toc/1932-6203Test
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4دورية أكاديمية
المؤلفون: Sonia Paco, Teresa Casserras, Maria Angels Rodríguez, Cristina Jou, Montserrat Puigdelloses, Carlos I Ortez, Jordi Diaz-Manera, Eduardo Gallardo, Jaume Colomer, Andrés Nascimento, Susana G Kalko, Cecilia Jimenez-Mallebrera
المصدر: PLoS ONE, Vol 10, Iss 12, p e0145107 (2015)
الوصف: BACKGROUND:Collagen VI related myopathies encompass a range of phenotypes with involvement of skeletal muscle, skin and other connective tissues. They represent a severe and relatively common form of congenital disease for which there is no treatment. Collagen VI in skeletal muscle and skin is produced by fibroblasts. AIMS & METHODS:In order to gain insight into the consequences of collagen VI mutations and identify key disease pathways we performed global gene expression analysis of dermal fibroblasts from patients with Ullrich Congenital Muscular Dystrophy with and without vitamin C treatment. The expression data were integrated using a range of systems biology tools. Results were validated by real-time PCR, western blotting and functional assays. FINDINGS:We found significant changes in the expression levels of almost 600 genes between collagen VI deficient and control fibroblasts. Highly regulated genes included extracellular matrix components and surface receptors, including integrins, indicating a shift in the interaction between the cell and its environment. This was accompanied by a significant increase in fibroblasts adhesion to laminin. The observed changes in gene expression profiling may be under the control of two miRNAs, miR-30c and miR-181a, which we found elevated in tissue and serum from patients and which could represent novel biomarkers for muscular dystrophy. Finally, the response to vitamin C of collagen VI mutated fibroblasts significantly differed from healthy fibroblasts. Vitamin C treatment was able to revert the expression of some key genes to levels found in control cells raising the possibility of a beneficial effect of vitamin C as a modulator of some of the pathological aspects of collagen VI related diseases.
وصف الملف: electronic resource
العلاقة: http://europepmc.org/articles/PMC4686057?pdf=renderTest; https://doaj.org/toc/1932-6203Test
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5دورية أكاديمية
المؤلفون: Jonàs Juan-Mateu, Lidia González-Quereda, Maria José Rodríguez, Edgard Verdura, Kira Lázaro, Cristina Jou, Andrés Nascimento, Cecilia Jiménez-Mallebrera, Jaume Colomer, Soledad Monges, Fabiana Lubieniecki, Maria Eugenia Foncuberta, Samuel Ignacio Pascual-Pascual, Jesús Molano, Montserrat Baiget, Pia Gallano
المصدر: PLoS ONE, Vol 8, Iss 3, p e59916 (2013)
الوصف: DMD nonsense and frameshift mutations lead to severe Duchenne muscular dystrophy while in-frame mutations lead to milder Becker muscular dystrophy. Exceptions are found in 10% of cases and the production of alternatively spliced transcripts is considered a key modifier of disease severity. Several exonic mutations have been shown to induce exon-skipping, while splice site mutations result in exon-skipping or activation of cryptic splice sites. However, factors determining the splicing pathway are still unclear. Point mutations provide valuable information regarding the regulation of pre-mRNA splicing and elements defining exon identity in the DMD gene. Here we provide a comprehensive analysis of 98 point mutations related to clinical phenotype and their effect on muscle mRNA and dystrophin expression. Aberrant splicing was found in 27 mutations due to alteration of splice sites or splicing regulatory elements. Bioinformatics analysis was performed to test the ability of the available algorithms to predict consequences on mRNA and to investigate the major factors that determine the splicing pathway in mutations affecting splicing signals. Our findings suggest that the splicing pathway is highly dependent on the interplay between splice site strength and density of regulatory elements.
وصف الملف: electronic resource
العلاقة: http://europepmc.org/articles/PMC3607557?pdf=renderTest; https://doaj.org/toc/1932-6203Test
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6دورية أكاديمية
المؤلفون: Sonia Paco, Susana G Kalko, Cristina Jou, María A Rodríguez, Joan Corbera, Francesco Muntoni, Lucy Feng, Eloy Rivas, Ferran Torner, Francesca Gualandi, Anna M Gomez-Foix, Anna Ferrer, Carlos Ortez, Andrés Nascimento, Jaume Colomer, Cecilia Jimenez-Mallebrera
المصدر: PLoS ONE, Vol 8, Iss 10, p e77430 (2013)
الوصف: Ullrich congenital muscular dystrophy (UCMD), caused by collagen VI deficiency, is a common congenital muscular dystrophy. At present, the role of collagen VI in muscle and the mechanism of disease are not fully understood. To address this we have applied microarrays to analyse the transcriptome of UCMD muscle and compare it to healthy muscle and other muscular dystrophies. We identified 389 genes which are differentially regulated in UCMD relative to controls. In addition, there were 718 genes differentially expressed between UCMD and dystrophin deficient muscle. In contrast, only 29 genes were altered relative to other congenital muscular dystrophies. Changes in gene expression were confirmed by real-time PCR. The set of regulated genes was analysed by Gene Ontology, KEGG pathways and Ingenuity Pathway analysis to reveal the molecular functions and gene networks associated with collagen VI defects. The most significantly regulated pathways were those involved in muscle regeneration, extracellular matrix remodelling and inflammation. We characterised the immune response in UCMD biopsies as being mainly mediated via M2 macrophages and the complement pathway indicating that anti-inflammatory treatment may be beneficial to UCMD as for other dystrophies. We studied the immunolocalisation of ECM components and found that biglycan, a collagen VI interacting proteoglycan, was reduced in the basal lamina of UCMD patients. We propose that biglycan reduction is secondary to collagen VI loss and that it may be contributing towards UCMD pathophysiology. Consequently, strategies aimed at over-expressing biglycan and restore the link between the muscle cell surface and the extracellular matrix should be considered.
وصف الملف: electronic resource
العلاقة: http://europepmc.org/articles/PMC3819505?pdf=renderTest; https://doaj.org/toc/1932-6203Test
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7دورية أكاديمية
المؤلفون: Emma Mormeneo, Cecilia Jimenez-Mallebrera, Xavier Palomer, Valeria De Nigris, Manuel Vázquez-Carrera, Anna Orozco, Andrés Nascimento, Jaume Colomer, Carles Lerín, Anna M Gómez-Foix
المصدر: PLoS ONE, Vol 7, Iss 1, p e29985 (2012)
الوصف: The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) is a chief activator of mitochondrial and metabolic programs and protects against atrophy in skeletal muscle (skm). Here we tested whether PGC-1α overexpression could restructure the transcriptome and metabolism of primary cultured human skm cells, which display a phenotype that resembles the atrophic phenotype. An oligonucleotide microarray analysis was used to reveal the effects of PGC-1α on the whole transcriptome. Fifty-three different genes showed altered expression in response to PGC-1α: 42 upregulated and 11 downregulated. The main gene ontologies (GO) associated with the upregulated genes were mitochondrial components and processes and this was linked with an increase in COX activity, an indicator of mitochondrial content. Furthermore, PGC-1α enhanced mitochondrial oxidation of palmitate and lactate to CO(2), but not glucose oxidation. The other most significantly associated GOs for the upregulated genes were chemotaxis and cytokine activity, and several cytokines, including IL-8/CXCL8, CXCL6, CCL5 and CCL8, were within the most highly induced genes. Indeed, PGC-1α highly increased IL-8 cell protein content. The most upregulated gene was PVALB, which is related to calcium signaling. Potential metabolic regulators of fatty acid and glucose storage were among mainly regulated genes. The mRNA and protein level of FITM1/FIT1, which enhances the formation of lipid droplets, was raised by PGC-1α, while in oleate-incubated cells PGC-1α increased the number of smaller lipid droplets and modestly triglyceride levels, compared to controls. CALM1, the calcium-modulated δ subunit of phosphorylase kinase, was downregulated by PGC-1α, while glycogen phosphorylase was inactivated and glycogen storage was increased by PGC-1α. In conclusion, of the metabolic transcriptome deficiencies of cultured skm cells, PGC-1α rescued the expression of genes encoding mitochondrial proteins and FITM1. Several myokine genes, including IL-8 and CCL5, which are known to be constitutively expressed in human skm cells, were induced by PGC-1α.
وصف الملف: electronic resource
العلاقة: http://europepmc.org/articles/PMC3260188?pdf=renderTest; https://doaj.org/toc/1932-6203Test
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8دورية أكاديمية
المؤلفون: Jaume Colomer
المصدر: Periférica, Vol 1, Iss 12 (2011)
مصطلحات موضوعية: Gestión, públicos culturales, marketing, tecnología, Social Sciences
الوصف: La diversidad de públicos culturales és un hecho evidente. La diversidad de intereses, gustos y universos personales hace necesaria una relación personalizada con los públicos potenciales de un proyecto cultural para conocerlos mejor, proponerles prácticas culturales de acuerdo con sus intereses y expectativas, para generar confianza recíproca que permita su implicación proactiva en el proyecto en forma de comunidad de intereses. El marketing y las tecnologías digitales nos dan instrumentos y metodologías que no podemos desaprovechar. El marketing relacional y las plataformas CRM nos pueden ayudar a construir relaciones duraderas con los públicos basadas en la confianza que fomenten el empoderamiento y la implicación. Pero hay que elaborar un Plan de Gestión de Públicos que defina prioridades y estrategias de acuerdo con la misión y los objetivos del proyecto. Se proponen cinco estrategias básicas de gestión de públicos a partir de una categorización de los mismos: diversificar, incrementar y regularizar las prácticas de los públicos activos; gestionar la comunidad de públicos implicados; captar nuevos públicos a partir de la demanda latente; invertir en la formación de gustos y valores en niños y adolescentes; crear interés por las prácticas culturales en públicos con demanda inexistente.
وصف الملف: electronic resource
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المؤلفون: Julita Medina, Jessica Expósito-Escudero, Andrés Nascimento, Cecilia Jimenez-Mallebrera, Laura Carrera-García, Juan José Lazaro, Daniel Cuadras, Carlos Ortez, Magda Bosch de Basea, Daniel Natera-de Benito, Jordi Muchart, Jaume Colomer
المصدر: European Journal of Paediatric Neurology. 31:92-101
مصطلحات موضوعية: Male, musculoskeletal diseases, medicine.medical_specialty, Adolescent, Oligonucleotides, Scoliosis, Radiography, Interventional, Neurosurgical Procedures, Muscular Atrophy, Spinal, 03 medical and health sciences, Imaging, Three-Dimensional, 0302 clinical medicine, Lumbar, 030225 pediatrics, Humans, Medicine, Child, Injections, Spinal, Cobb angle, medicine.diagnostic_test, business.industry, Lumbar puncture, Decision Trees, Infant, General Medicine, Spinal muscular atrophy, medicine.disease, SMA, Surgery, Spinal anatomy, Child, Preschool, Pediatrics, Perinatology and Child Health, Feasibility Studies, Female, Nusinersen, Neurology (clinical), Tomography, X-Ray Computed, business, Algorithms, 030217 neurology & neurosurgery
الوصف: The approval of nusinersen for the treatment of spinal muscular atrophy (SMA) has significantly changed the natural history of the disease. Nevertheless, scoliosis secondary to axial muscle weakness occurs at some point in most of patients with SMA and a conventional posterior interlaminar approach for intrathecal administration of nusinersen can be particularly challenging to perform in patients with severe scoliosis and/or previous spine fusion surgeries. We developed a protocol for the administration of nusinersen in pediatric patients, which includes a decision-tree algorithm that categorizes patients according to the estimated technical difficulty for the intrathecal administration. Complex spine patients were defined as those with a Cobb angle greater than 50° and/or a history of spinal surgery, while the rest of patients were considered non-complex. Nusinersen was successfully administered through a conventional non-CT-guided lumbar puncture in all 14 non-complex spine patients (110 out of 110 procedures; 100%). The feasibility of the intrathecal injection in the 15 complex spine patients was assessed by 3D CT. Administration was considered unfeasible in 7 out of these 15 patients according to imaging. In the 8 complex spine patients in whom the administration was considered feasible, conventional non-CT-guided lumbar punctures were successful only in 19 out of 53 procedures (36%). The remaining 34 procedures (64%) were guided by CT scan, all successful. Our work demonstrates that a cut-off point of 50° in Cobb angle and history of spinal surgery can reliably be used to anticipate the need for CT guidance in nusinersen administration.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::86830f9eea863686abc9710a8780b214Test
https://doi.org/10.1016/j.ejpn.2021.02.009Test -
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المؤلفون: Jessica Expósito-Escudero, Cristina Jou, J. Corbera, Daniel Cuadras, Obdulia Moya, Julita Medina, Daniel Natera-de Benito, Veronica Saez, Jaume Colomer, Lidia Gonzalez-Quereda, Edna Julieth Bobadilla-Quesada, María Eugenia Yoldi, Cecilia Jimenez-Mallebrera, Pia Gallano, Carlos Ortez, Laura Carrera-García, Andrés Nascimento, A. Codina
المصدر: NEUROMUSCULAR DISORDERS
r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname
r-IIB SANT PAU: Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
Institut dInvestigació Biomèdica Sant Pau (IIB Sant Pau)
r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
r-FSJD: Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
Fundació Sant Joan de Déuمصطلحات موضوعية: Adult, Male, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Scoliosis, Disease, Muscular Dystrophies, Congenital myasthenic syndrome, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Term effect, In patient, Muscular dystrophy, Dystroglycans, Genetics (clinical), Pyridostigmine, Myasthenic Syndromes, Congenital, business.industry, medicine.disease, Nucleotidyltransferases, Response to treatment, Dystroglycanopathy, 030104 developmental biology, Muscular Dystrophies, Limb-Girdle, Neurology, Pediatrics, Perinatology and Child Health, Female, Gmppb, Neurology (clinical), business, Motor functional scales, 030217 neurology & neurosurgery, Pyridostigmine Bromide, medicine.drug
الوصف: GMPPB mutations cause congenital myasthenic syndromes (CMS) overlapping with muscular dystrophy. Treatment with pyridostigmine has been reported to be effective in those patients. Nevertheless, results of functional motor assessments to determine its precise impact on the short and long term were not available. We describe the response to treatment with pyridostigmine in three siblings with GMPPB-related CMS using functional motor scales performed regularly over a period of 40 months. The beneficial effect of the treatment was outstanding within the first hours, with all the scales showing a dramatic increase in only two days. This remarkable improvement remained steady during 12 months but a moderate decrease was subsequently detected in two of the three patients. Despite this decline in the scores of the scales at the end of follow up, the functional motor status of the patients was still significantly better than it was before starting treatment. The introduction of pyridostigmine at an early age of the disease in one of the patients, before the onset of scoliosis, may have had a protective effect on it. (C) 2020 Elsevier B.V. All rights reserved.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0d00ad6d5fbbf5ed1276d00e253cf71dTest
https://doi.org/10.1016/j.nmd.2020.07.009Test
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