<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Moura, David S</style></author><author><style face="normal" font="default" size="100%">Mondaza-Hernandez, Jose L</style></author><author><style face="normal" font="default" size="100%">Sanchez-Bustos, Paloma</style></author><author><style face="normal" font="default" size="100%">Peña-Chilet, Maria</style></author><author><style face="normal" font="default" size="100%">Cordero-Varela, Juan A</style></author><author><style face="normal" font="default" size="100%">Lopez-Alvarez, Maria</style></author><author><style face="normal" font="default" size="100%">Carrillo-Garcia, Jaime</style></author><author><style face="normal" font="default" size="100%">Martin-Ruiz, Marta</style></author><author><style face="normal" font="default" size="100%">Romero-Gonzalez, Pablo</style></author><author><style face="normal" font="default" size="100%">Renshaw-Calderon, Marta</style></author><author><style face="normal" font="default" size="100%">Ramos, Rafael</style></author><author><style face="normal" font="default" size="100%">Marcilla, David</style></author><author><style face="normal" font="default" size="100%">Alvarez-Alegret, Ramiro</style></author><author><style face="normal" font="default" size="100%">Agra-Pujol, Carolina</style></author><author><style face="normal" font="default" size="100%">Izquierdo, Francisco</style></author><author><style face="normal" font="default" size="100%">Ortega-Medina, Luis</style></author><author><style face="normal" font="default" size="100%">Martin-Davila, Francisco</style></author><author><style face="normal" font="default" size="100%">Hernandez-Leon, Carmen Nieves</style></author><author><style face="normal" font="default" size="100%">Romagosa, Cleofe</style></author><author><style face="normal" font="default" size="100%">Salgado, Maria Angeles Vaz</style></author><author><style face="normal" font="default" size="100%">Lavernia, Javier</style></author><author><style face="normal" font="default" size="100%">Bagué, Silvia</style></author><author><style face="normal" font="default" size="100%">Mayodormo-Aranda, Empar</style></author><author><style face="normal" font="default" size="100%">Alvarez, Rosa</style></author><author><style face="normal" font="default" size="100%">Valverde, Claudia</style></author><author><style face="normal" font="default" size="100%">Martinez-Trufero, Javier</style></author><author><style face="normal" font="default" size="100%">Castilla-Ramirez, Carolina</style></author><author><style face="normal" font="default" size="100%">Gutierrez, Antonio</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author><author><style face="normal" font="default" size="100%">Hindi, Nadia</style></author><author><style face="normal" font="default" size="100%">Garcia-Foncillas, Jesus</style></author><author><style face="normal" font="default" size="100%">Martin-Broto, Javier</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">HMGA1 regulates trabectedin sensitivity in advanced soft-tissue sarcoma (STS): A Spanish Group for Research on Sarcomas (GEIS) study.</style></title><secondary-title><style face="normal" font="default" size="100%">Cell Mol Life Sci</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Cell Mol Life Sci</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Antineoplastic Agents, Alkylating</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Line, Tumor</style></keyword><keyword><style  face="normal" font="default" size="100%">Drug Resistance, Neoplasm</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression Regulation, Neoplastic</style></keyword><keyword><style  face="normal" font="default" size="100%">HMGA1a Protein</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Leiomyosarcoma</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Prognosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Sarcoma</style></keyword><keyword><style  face="normal" font="default" size="100%">Signal Transduction</style></keyword><keyword><style  face="normal" font="default" size="100%">TOR Serine-Threonine Kinases</style></keyword><keyword><style  face="normal" font="default" size="100%">Trabectedin</style></keyword><keyword><style  face="normal" font="default" size="100%">Xenograft Model Antitumor Assays</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2024</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2024 May 17</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">81</style></volume><pages><style face="normal" font="default" size="100%">219</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;HMGA1 is a structural epigenetic chromatin factor that has been associated with tumor progression and drug resistance. Here, we reported the prognostic/predictive value of HMGA1 for trabectedin in advanced soft-tissue sarcoma (STS) and the effect of inhibiting HMGA1 or the mTOR downstream pathway in trabectedin activity. The prognostic/predictive value of HMGA1 expression was assessed in a cohort of 301 STS patients at mRNA (n = 133) and protein level (n = 272), by HTG EdgeSeq transcriptomics and immunohistochemistry, respectively. The effect of HMGA1 silencing on trabectedin activity and gene expression profiling was measured in leiomyosarcoma cells. The effect of combining mTOR inhibitors with trabectedin was assessed on cell viability in vitro studies, whereas in vivo studies tested the activity of this combination. HMGA1 mRNA and protein expression were significantly associated with worse progression-free survival of trabectedin and worse overall survival in STS. HMGA1 silencing sensitized leiomyosarcoma cells for trabectedin treatment, reducing the spheroid area and increasing cell death. The downregulation of HGMA1 significantly decreased the enrichment of some specific gene sets, including the PI3K/AKT/mTOR pathway. The inhibition of mTOR, sensitized leiomyosarcoma cultures for trabectedin treatment, increasing cell death. In in vivo studies, the combination of rapamycin with trabectedin downregulated HMGA1 expression and stabilized tumor growth of 3-methylcholantrene-induced sarcoma-like models. HMGA1 is an adverse prognostic factor for trabectedin treatment in advanced STS. HMGA1 silencing increases trabectedin efficacy, in part by modulating the mTOR signaling pathway. Trabectedin plus mTOR inhibitors are active in preclinical models of sarcoma, downregulating HMGA1 expression levels and stabilizing tumor growth.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">1</style></issue></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Esteban-Medina, Marina</style></author><author><style face="normal" font="default" size="100%">Loucera, Carlos</style></author><author><style face="normal" font="default" size="100%">Rian, Kinza</style></author><author><style face="normal" font="default" size="100%">Velasco, Sheyla</style></author><author><style face="normal" font="default" size="100%">Olivares-González, Lorena</style></author><author><style face="normal" font="default" size="100%">Rodrigo, Regina</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author><author><style face="normal" font="default" size="100%">Peña-Chilet, Maria</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">The mechanistic functional landscape of retinitis pigmentosa: a machine learning-driven approach to therapeutic target discovery.</style></title><secondary-title><style face="normal" font="default" size="100%">J Transl Med</style></secondary-title><alt-title><style face="normal" font="default" size="100%">J Transl Med</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Retinitis pigmentosa</style></keyword><keyword><style  face="normal" font="default" size="100%">Signal Transduction</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2024</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2024 Feb 06</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">22</style></volume><pages><style face="normal" font="default" size="100%">139</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;Retinitis pigmentosa is the prevailing genetic cause of blindness in developed nations with no effective treatments. In the pursuit of unraveling the intricate dynamics underlying this complex disease, mechanistic models emerge as a tool of proven efficiency rooted in systems biology, to elucidate the interplay between RP genes and their mechanisms. The integration of mechanistic models and drug-target interactions under the umbrella of machine learning methodologies provides a multifaceted approach that can boost the discovery of novel therapeutic targets, facilitating further drug repurposing in RP.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;By mapping Retinitis Pigmentosa-related genes (obtained from Orphanet, OMIM and HPO databases) onto KEGG signaling pathways, a collection of signaling functional circuits encompassing Retinitis Pigmentosa molecular mechanisms was defined. Next, a mechanistic model of the so-defined disease map, where the effects of interventions can be simulated, was built. Then, an explainable multi-output random forest regressor was trained using normal tissue transcriptomic data to learn causal connections between targets of approved drugs from DrugBank and the functional circuits of the mechanistic disease map. Selected target genes involvement were validated on rd10 mice, a murine model of Retinitis Pigmentosa.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;A mechanistic functional map of Retinitis Pigmentosa was constructed resulting in 226 functional circuits belonging to 40 KEGG signaling pathways. The method predicted 109 targets of approved drugs in use with a potential effect over circuits corresponding to nine hallmarks identified. Five of those targets were selected and experimentally validated in rd10 mice: Gabre, Gabra1 (GABARα1 protein), Slc12a5 (KCC2 protein), Grin1 (NR1 protein) and Glr2a. As a result, we provide a resource to evaluate the potential impact of drug target genes in Retinitis Pigmentosa.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;The possibility of building actionable disease models in combination with machine learning algorithms to learn causal drug-disease interactions opens new avenues for boosting drug discovery. Such mechanistically-based hypotheses can guide and accelerate the experimental validations prioritizing drug target candidates. In this work, a mechanistic model describing the functional disease map of Retinitis Pigmentosa was developed, identifying five promising therapeutic candidates targeted by approved drug. Further experimental validation will demonstrate the efficiency of this approach for a systematic application to other rare diseases.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">1</style></issue></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">León, Carlos</style></author><author><style face="normal" font="default" size="100%">Garcia-Garcia, Francisco</style></author><author><style face="normal" font="default" size="100%">Llames, Sara</style></author><author><style face="normal" font="default" size="100%">García-Pérez, Eva</style></author><author><style face="normal" font="default" size="100%">Carretero, Marta</style></author><author><style face="normal" font="default" size="100%">Arriba, María Del Carmen</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author><author><style face="normal" font="default" size="100%">Del Rio, Marcela</style></author><author><style face="normal" font="default" size="100%">Escamez, Maria José</style></author><author><style face="normal" font="default" size="100%">Martínez-Santamaría, Lucía</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Transcriptomic Analysis of a Diabetic Skin-Humanized Mouse Model Dissects Molecular Pathways Underlying the Delayed Wound Healing Response.</style></title><secondary-title><style face="normal" font="default" size="100%">Genes (Basel)</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Genes (Basel)</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Diabetes Mellitus, Experimental</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression Profiling</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression Regulation</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene ontology</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Metabolic Networks and Pathways</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice, Nude</style></keyword><keyword><style  face="normal" font="default" size="100%">Microarray Analysis</style></keyword><keyword><style  face="normal" font="default" size="100%">Molecular Sequence Annotation</style></keyword><keyword><style  face="normal" font="default" size="100%">Principal Component Analysis</style></keyword><keyword><style  face="normal" font="default" size="100%">Signal Transduction</style></keyword><keyword><style  face="normal" font="default" size="100%">Skin</style></keyword><keyword><style  face="normal" font="default" size="100%">Skin Transplantation</style></keyword><keyword><style  face="normal" font="default" size="100%">Skin Ulcer</style></keyword><keyword><style  face="normal" font="default" size="100%">Streptozocin</style></keyword><keyword><style  face="normal" font="default" size="100%">Tissue Engineering</style></keyword><keyword><style  face="normal" font="default" size="100%">Transcriptome</style></keyword><keyword><style  face="normal" font="default" size="100%">Transplantation, Heterologous</style></keyword><keyword><style  face="normal" font="default" size="100%">Wound Healing</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2020</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2020 12 31</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">12</style></volume><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Defective healing leading to cutaneous ulcer formation is one of the most feared complications of diabetes due to its consequences on patients' quality of life and on the healthcare system. A more in-depth analysis of the underlying molecular pathophysiology is required to develop effective healing-promoting therapies for those patients. Major architectural and functional differences with human epidermis limit extrapolation of results coming from rodents and other small mammal-healing models. Therefore, the search for reliable humanized models has become mandatory. Previously, we developed a diabetes-induced delayed humanized wound healing model that faithfully recapitulated the major histological features of such skin repair-deficient condition. Herein, we present the results of a transcriptomic and functional enrichment analysis followed by a mechanistic analysis performed in such humanized wound healing model. The deregulation of genes implicated in functions such as angiogenesis, apoptosis, and inflammatory signaling processes were evidenced, confirming published data in diabetic patients that in fact might also underlie some of the histological features previously reported in the delayed skin-humanized healing model. Altogether, these molecular findings support the utility of such preclinical model as a valuable tool to gain insight into the molecular basis of the delayed diabetic healing with potential impact in the translational medicine field.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">1</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/33396192?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Cobo-Vuilleumier, Nadia</style></author><author><style face="normal" font="default" size="100%">Lorenzo, Petra I</style></author><author><style face="normal" font="default" size="100%">Rodríguez, Noelia García</style></author><author><style face="normal" font="default" size="100%">Herrera Gómez, Irene de Gracia</style></author><author><style face="normal" font="default" size="100%">Fuente-Martin, Esther</style></author><author><style face="normal" font="default" size="100%">López-Noriega, Livia</style></author><author><style face="normal" font="default" size="100%">Mellado-Gil, José Manuel</style></author><author><style face="normal" font="default" size="100%">Romero-Zerbo, Silvana-Yanina</style></author><author><style face="normal" font="default" size="100%">Baquié, Mathurin</style></author><author><style face="normal" font="default" size="100%">Lachaud, Christian Claude</style></author><author><style face="normal" font="default" size="100%">Stifter, Katja</style></author><author><style face="normal" font="default" size="100%">Perdomo, German</style></author><author><style face="normal" font="default" size="100%">Bugliani, Marco</style></author><author><style face="normal" font="default" size="100%">De Tata, Vincenzo</style></author><author><style face="normal" font="default" size="100%">Bosco, Domenico</style></author><author><style face="normal" font="default" size="100%">Parnaud, Geraldine</style></author><author><style face="normal" font="default" size="100%">Pozo, David</style></author><author><style face="normal" font="default" size="100%">Hmadcha, Abdelkrim</style></author><author><style face="normal" font="default" size="100%">Florido, Javier P</style></author><author><style face="normal" font="default" size="100%">Toscano, Miguel G</style></author><author><style face="normal" font="default" size="100%">de Haan, Peter</style></author><author><style face="normal" font="default" size="100%">Schoonjans, Kristina</style></author><author><style face="normal" font="default" size="100%">Sánchez Palazón, Luis</style></author><author><style face="normal" font="default" size="100%">Marchetti, Piero</style></author><author><style face="normal" font="default" size="100%">Schirmbeck, Reinhold</style></author><author><style face="normal" font="default" size="100%">Martín-Montalvo, Alejandro</style></author><author><style face="normal" font="default" size="100%">Meda, Paolo</style></author><author><style face="normal" font="default" size="100%">Soria, Bernat</style></author><author><style face="normal" font="default" size="100%">Bermúdez-Silva, Francisco-Javier</style></author><author><style face="normal" font="default" size="100%">St-Onge, Luc</style></author><author><style face="normal" font="default" size="100%">Gauthier, Benoit R</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus.</style></title><secondary-title><style face="normal" font="default" size="100%">Nat Commun</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Nat Commun</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Apoptosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Communication</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Survival</style></keyword><keyword><style  face="normal" font="default" size="100%">Diabetes Mellitus, Experimental</style></keyword><keyword><style  face="normal" font="default" size="100%">Diabetes Mellitus, Type 2</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression Regulation</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Hypoglycemic Agents</style></keyword><keyword><style  face="normal" font="default" size="100%">Immunity, Innate</style></keyword><keyword><style  face="normal" font="default" size="100%">insulin</style></keyword><keyword><style  face="normal" font="default" size="100%">Insulin-Secreting Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Islets of Langerhans</style></keyword><keyword><style  face="normal" font="default" size="100%">Islets of Langerhans Transplantation</style></keyword><keyword><style  face="normal" font="default" size="100%">Macrophages</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice, Inbred C57BL</style></keyword><keyword><style  face="normal" font="default" size="100%">Phenalenes</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptors, Cytoplasmic and Nuclear</style></keyword><keyword><style  face="normal" font="default" size="100%">Streptozocin</style></keyword><keyword><style  face="normal" font="default" size="100%">T-Lymphocytes, Regulatory</style></keyword><keyword><style  face="normal" font="default" size="100%">Transplantation, Heterologous</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2018</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2018 Apr 16</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">9</style></volume><pages><style face="normal" font="default" size="100%">1488</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Type 1 diabetes mellitus (T1DM) is due to the selective destruction of islet beta cells by immune cells. Current therapies focused on repressing the immune attack or stimulating beta cell regeneration still have limited clinical efficacy. Therefore, it is timely to identify innovative targets to dampen the immune process, while promoting beta cell survival and function. Liver receptor homologue-1 (LRH-1) is a nuclear receptor that represses inflammation in digestive organs, and protects pancreatic islets against apoptosis. Here, we show that BL001, a small LRH-1 agonist, impedes hyperglycemia progression and the immune-dependent inflammation of pancreas in murine models of T1DM, and beta cell apoptosis in islets of type 2 diabetic patients, while increasing beta cell mass and insulin secretion. Thus, we suggest that LRH-1 agonism favors a dialogue between immune and islet cells, which could be druggable to protect against diabetes mellitus.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">1</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/29662071?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Prieto, Javier</style></author><author><style face="normal" font="default" size="100%">León, Marian</style></author><author><style face="normal" font="default" size="100%">Ponsoda, Xavier</style></author><author><style face="normal" font="default" size="100%">Garcia-Garcia, Francisco</style></author><author><style face="normal" font="default" size="100%">Bort, Roque</style></author><author><style face="normal" font="default" size="100%">Serna, Eva</style></author><author><style face="normal" font="default" size="100%">Barneo-Muñoz, Manuela</style></author><author><style face="normal" font="default" size="100%">Palau, Francesc</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author><author><style face="normal" font="default" size="100%">López-García, Carlos</style></author><author><style face="normal" font="default" size="100%">Torres, Josema</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Dysfunctional mitochondrial fission impairs cell reprogramming.</style></title><secondary-title><style face="normal" font="default" size="100%">Cell Cycle</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Cell Cycle</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Cycle Checkpoints</style></keyword><keyword><style  face="normal" font="default" size="100%">Cellular Reprogramming</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA Damage</style></keyword><keyword><style  face="normal" font="default" size="100%">G2 Phase</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Knockdown Techniques</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Mitochondrial Dynamics</style></keyword><keyword><style  face="normal" font="default" size="100%">Mitosis</style></keyword><keyword><style  face="normal" font="default" size="100%">Nerve Tissue Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Pluripotent Stem Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Transcription Factors</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2016</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2016 Dec</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">15</style></volume><pages><style face="normal" font="default" size="100%">3240-3250</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;We have recently shown that mitochondrial fission is induced early in reprogramming in a Drp1-dependent manner; however, the identity of the factors controlling Drp1 recruitment to mitochondria was unexplored. To investigate this, we used a panel of RNAi targeting factors involved in the regulation of mitochondrial dynamics and we observed that MiD51, Gdap1 and, to a lesser extent, Mff were found to play key roles in this process. Cells derived from Gdap1-null mice were used to further explore the role of this factor in cell reprogramming. Microarray data revealed a prominent down-regulation of cell cycle pathways in Gdap1-null cells early in reprogramming and cell cycle profiling uncovered a G2/M growth arrest in Gdap1-null cells undergoing reprogramming. High-Content analysis showed that this growth arrest was DNA damage-independent. We propose that lack of efficient mitochondrial fission impairs cell reprogramming by interfering with cell cycle progression in a DNA damage-independent manner.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">23</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/27753531?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Corton, M</style></author><author><style face="normal" font="default" size="100%">Avila-Fernández, A</style></author><author><style face="normal" font="default" size="100%">Campello, L</style></author><author><style face="normal" font="default" size="100%">Sánchez, M</style></author><author><style face="normal" font="default" size="100%">Benavides, B</style></author><author><style face="normal" font="default" size="100%">López-Molina, M I</style></author><author><style face="normal" font="default" size="100%">Fernández-Sánchez, L</style></author><author><style face="normal" font="default" size="100%">Sánchez-Alcudia, R</style></author><author><style face="normal" font="default" size="100%">da Silva, L R J</style></author><author><style face="normal" font="default" size="100%">Reyes, N</style></author><author><style face="normal" font="default" size="100%">Martín-Garrido, E</style></author><author><style face="normal" font="default" size="100%">Zurita, O</style></author><author><style face="normal" font="default" size="100%">Fernández-San José, P</style></author><author><style face="normal" font="default" size="100%">Pérez-Carro, R</style></author><author><style face="normal" font="default" size="100%">García-García, F</style></author><author><style face="normal" font="default" size="100%">Dopazo, J</style></author><author><style face="normal" font="default" size="100%">García-Sandoval, B</style></author><author><style face="normal" font="default" size="100%">Cuenca, N</style></author><author><style face="normal" font="default" size="100%">Ayuso, C</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Identification of the Photoreceptor Transcriptional Co-Repressor SAMD11 as Novel Cause of Autosomal Recessive Retinitis Pigmentosa.</style></title><secondary-title><style face="normal" font="default" size="100%">Sci Rep</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Sci Rep</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Co-Repressor Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Codon, Nonsense</style></keyword><keyword><style  face="normal" font="default" size="100%">Cohort Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Comparative Genomic Hybridization</style></keyword><keyword><style  face="normal" font="default" size="100%">Consanguinity</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA Mutational Analysis</style></keyword><keyword><style  face="normal" font="default" size="100%">Exome</style></keyword><keyword><style  face="normal" font="default" size="100%">Eye Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression Regulation</style></keyword><keyword><style  face="normal" font="default" size="100%">Genes, Recessive</style></keyword><keyword><style  face="normal" font="default" size="100%">Homeodomain Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Homozygote</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Middle Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Single Nucleotide</style></keyword><keyword><style  face="normal" font="default" size="100%">Protein Interaction Mapping</style></keyword><keyword><style  face="normal" font="default" size="100%">Retina</style></keyword><keyword><style  face="normal" font="default" size="100%">Retinal Dystrophies</style></keyword><keyword><style  face="normal" font="default" size="100%">Retinal Rod Photoreceptor Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Retinitis pigmentosa</style></keyword><keyword><style  face="normal" font="default" size="100%">Spain</style></keyword><keyword><style  face="normal" font="default" size="100%">Trans-Activators</style></keyword><keyword><style  face="normal" font="default" size="100%">Transcription Factors</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2016</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2016 Oct 13</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">6</style></volume><pages><style face="normal" font="default" size="100%">35370</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Retinitis pigmentosa (RP), the most frequent form of inherited retinal dystrophy is characterized by progressive photoreceptor degeneration. Many genes have been implicated in RP development, but several others remain to be identified. Using a combination of homozygosity mapping, whole-exome and targeted next-generation sequencing, we found a novel homozygous nonsense mutation in SAMD11 in five individuals diagnosed with adult-onset RP from two unrelated consanguineous Spanish families. SAMD11 is ortholog to the mouse major retinal SAM domain (mr-s) protein that is implicated in CRX-mediated transcriptional regulation in the retina. Accordingly, protein-protein network analysis revealed a significant interaction of SAMD11 with CRX. Immunoblotting analysis confirmed strong expression of SAMD11 in human retina. Immunolocalization studies revealed SAMD11 was detected in the three nuclear layers of the human retina and interestingly differential expression between cone and rod photoreceptors was observed. Our study strongly implicates SAMD11 as novel cause of RP playing an important role in the pathogenesis of human degeneration of photoreceptors.&lt;/p&gt;</style></abstract><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/27734943?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Sevilla, Teresa</style></author><author><style face="normal" font="default" size="100%">Lupo, Vincenzo</style></author><author><style face="normal" font="default" size="100%">Martínez-Rubio, Dolores</style></author><author><style face="normal" font="default" size="100%">Sancho, Paula</style></author><author><style face="normal" font="default" size="100%">Sivera, Rafael</style></author><author><style face="normal" font="default" size="100%">Chumillas, María J</style></author><author><style face="normal" font="default" size="100%">García-Romero, Mar</style></author><author><style face="normal" font="default" size="100%">Pascual-Pascual, Samuel I</style></author><author><style face="normal" font="default" size="100%">Muelas, Nuria</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author><author><style face="normal" font="default" size="100%">Vílchez, Juan J</style></author><author><style face="normal" font="default" size="100%">Palau, Francesc</style></author><author><style face="normal" font="default" size="100%">Espinós, Carmen</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Mutations in the MORC2 gene cause axonal Charcot-Marie-Tooth disease.</style></title><secondary-title><style face="normal" font="default" size="100%">Brain</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Brain</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adult</style></keyword><keyword><style  face="normal" font="default" size="100%">Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Axons</style></keyword><keyword><style  face="normal" font="default" size="100%">Charcot-Marie-Tooth Disease</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">gene expression</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Infant</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Middle Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">mutation</style></keyword><keyword><style  face="normal" font="default" size="100%">Pedigree</style></keyword><keyword><style  face="normal" font="default" size="100%">Phenotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Sciatic Nerve</style></keyword><keyword><style  face="normal" font="default" size="100%">Sural Nerve</style></keyword><keyword><style  face="normal" font="default" size="100%">Transcription Factors</style></keyword><keyword><style  face="normal" font="default" size="100%">Young Adult</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2016</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2016 Jan</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">139</style></volume><pages><style face="normal" font="default" size="100%">62-72</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Charcot-Marie-Tooth disease (CMT) is a complex disorder with wide genetic heterogeneity. Here we present a new axonal Charcot-Marie-Tooth disease form, associated with the gene microrchidia family CW-type zinc finger 2 (MORC2). Whole-exome sequencing in a family with autosomal dominant segregation identified the novel MORC2 p.R190W change in four patients. Further mutational screening in our axonal Charcot-Marie-Tooth disease clinical series detected two additional sporadic cases, one patient who also carried the same MORC2 p.R190W mutation and another patient that harboured a MORC2 p.S25L mutation. Genetic and in silico studies strongly supported the pathogenicity of these sequence variants. The phenotype was variable and included patients with congenital or infantile onset, as well as others whose symptoms started in the second decade. The patients with early onset developed a spinal muscular atrophy-like picture, whereas in the later onset cases, the initial symptoms were cramps, distal weakness and sensory impairment. Weakness and atrophy progressed in a random and asymmetric fashion and involved limb girdle muscles, leading to a severe incapacity in adulthood. Sensory loss was always prominent and proportional to disease severity. Electrophysiological studies were consistent with an asymmetric axonal motor and sensory neuropathy, while fasciculations and myokymia were recorded rather frequently by needle electromyography. Sural nerve biopsy revealed pronounced multifocal depletion of myelinated fibres with some regenerative clusters and occasional small onion bulbs. Morc2 is expressed in both axons and Schwann cells of mouse peripheral nerve. Different roles in biological processes have been described for MORC2. As the silencing of Charcot-Marie-Tooth disease genes have been associated with DNA damage response, it is tempting to speculate that a deregulation of this pathway may be linked to the axonal degeneration observed in MORC2 neuropathy, thus adding a new pathogenic mechanism to the long list of causes of Charcot-Marie-Tooth disease. &lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">Pt 1</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/26497905?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Sánchez-Tena, Susana</style></author><author><style face="normal" font="default" size="100%">Lizarraga, Daneida</style></author><author><style face="normal" font="default" size="100%">Miranda, Anibal</style></author><author><style face="normal" font="default" size="100%">Vinardell, Maria P</style></author><author><style face="normal" font="default" size="100%">Garcia-Garcia, Francisco</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author><author><style face="normal" font="default" size="100%">Torres, Josep L</style></author><author><style face="normal" font="default" size="100%">Saura-Calixto, Fulgencio</style></author><author><style face="normal" font="default" size="100%">Capellà, Gabriel</style></author><author><style face="normal" font="default" size="100%">Cascante, Marta</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Grape antioxidant dietary fiber inhibits intestinal polyposis in ApcMin/+ mice: relation to cell cycle and immune response.</style></title><secondary-title><style face="normal" font="default" size="100%">Carcinogenesis</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Carcinogenesis</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Antioxidants</style></keyword><keyword><style  face="normal" font="default" size="100%">Body Weight</style></keyword><keyword><style  face="normal" font="default" size="100%">Carcinogenesis</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Cycle</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Cycle Checkpoints</style></keyword><keyword><style  face="normal" font="default" size="100%">Colorectal Neoplasms</style></keyword><keyword><style  face="normal" font="default" size="100%">Dietary Fiber</style></keyword><keyword><style  face="normal" font="default" size="100%">Dietary Supplements</style></keyword><keyword><style  face="normal" font="default" size="100%">Down-Regulation</style></keyword><keyword><style  face="normal" font="default" size="100%">G1 Phase</style></keyword><keyword><style  face="normal" font="default" size="100%">Inflammation</style></keyword><keyword><style  face="normal" font="default" size="100%">Intestinal Polyposis</style></keyword><keyword><style  face="normal" font="default" size="100%">Intestinal Polyps</style></keyword><keyword><style  face="normal" font="default" size="100%">Intestine, Small</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Transcriptome</style></keyword><keyword><style  face="normal" font="default" size="100%">Vitis</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2013</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2013 Aug</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">34</style></volume><pages><style face="normal" font="default" size="100%">1881-8</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Epidemiological and experimental studies suggest that fiber and phenolic compounds might have a protective effect on the development of colon cancer in humans. Accordingly, we assessed the chemopreventive efficacy and associated mechanisms of action of a lyophilized red grape pomace containing proanthocyanidin (PA)-rich dietary fiber [grape antioxidant dietary fiber (GADF)] on spontaneous intestinal tumorigenesis in the Apc(Min/+) mouse model. Mice were fed a standard diet (control group) or a 1% (w/w) GADF-supplemented diet (GADF group) for 6 weeks. GADF supplementation greatly reduced intestinal tumorigenesis, significantly decreasing the total number of polyps by 76%. Moreover, size distribution analysis showed a considerable reduction in all polyp size categories [diameter &lt;1mm (65%), 1-2mm (67%) and &gt;2mm (87%)]. In terms of polyp formation in the proximal, middle and distal portions of the small intestine, a decrease of 76, 81 and 73% was observed, respectively. Putative molecular mechanisms underlying the inhibition of intestinal tumorigenesis were investigated by comparison of microarray expression profiles of GADF-treated and non-treated mice. We observed that the effects of GADF are mainly associated with the induction of a G1 cell cycle arrest and the downregulation of genes related to the immune response and inflammation. Our findings show for the first time the efficacy and associated mechanisms of action of GADF against intestinal tumorigenesis in Apc(Min/+) mice, suggesting its potential for the prevention of colorectal cancer. &lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">8</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/23615403?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Sebastián-Leon, Patricia</style></author><author><style face="normal" font="default" size="100%">Carbonell, José</style></author><author><style face="normal" font="default" size="100%">Salavert, Francisco</style></author><author><style face="normal" font="default" size="100%">Sánchez, Rubén</style></author><author><style face="normal" font="default" size="100%">Medina, Ignacio</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Inferring the functional effect of gene expression changes in signaling pathways.</style></title><secondary-title><style face="normal" font="default" size="100%">Nucleic Acids Res</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Nucleic Acids Res</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Internet</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Models, Statistical</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptors, Cell Surface</style></keyword><keyword><style  face="normal" font="default" size="100%">Signal Transduction</style></keyword><keyword><style  face="normal" font="default" size="100%">Software</style></keyword><keyword><style  face="normal" font="default" size="100%">Transcriptome</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2013</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2013 Jul</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">41</style></volume><pages><style face="normal" font="default" size="100%">W213-7</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Signaling pathways constitute a valuable source of information that allows interpreting the way in which alterations in gene activities affect to particular cell functionalities. There are web tools available that allow viewing and editing pathways, as well as representing experimental data on them. However, few methods aimed to identify the signaling circuits, within a pathway, associated to the biological problem studied exist and none of them provide a convenient graphical web interface. We present PATHiWAYS, a web-based signaling pathway visualization system that infers changes in signaling that affect cell functionality from the measurements of gene expression values in typical expression microarray case-control experiments. A simple probabilistic model of the pathway is used to estimate the probabilities for signal transmission from any receptor to any final effector molecule (taking into account the pathway topology) using for this the individual probabilities of gene product presence/absence inferred from gene expression values. Significant changes in these probabilities allow linking different cell functionalities triggered by the pathway to the biological problem studied. PATHiWAYS is available at: http://pathiways.babelomics.org/. &lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">Web Server issue</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/23748960?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Ventoso, Iván</style></author><author><style face="normal" font="default" size="100%">Kochetov, Alex</style></author><author><style face="normal" font="default" size="100%">Montaner, David</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author><author><style face="normal" font="default" size="100%">Santoyo, Javier</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Extensive translatome remodeling during ER stress response in mammalian cells.</style></title><secondary-title><style face="normal" font="default" size="100%">PLoS One</style></secondary-title><alt-title><style face="normal" font="default" size="100%">PLoS One</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Endoplasmic Reticulum Stress</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Jurkat Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">NIH 3T3 Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Oligonucleotide Array Sequence Analysis</style></keyword><keyword><style  face="normal" font="default" size="100%">Protein Biosynthesis</style></keyword><keyword><style  face="normal" font="default" size="100%">RNA, Messenger</style></keyword><keyword><style  face="normal" font="default" size="100%">Transcription, Genetic</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2012</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2012</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">7</style></volume><pages><style face="normal" font="default" size="100%">e35915</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;In this work we have described the translatome of two mammalian cell lines, NIH3T3 and Jurkat, by scoring the relative polysome association of ∼10,000 mRNA under normal and ER stress conditions. We have found that translation efficiencies of mRNA correlated poorly with transcript abundance, although a general tendency was observed so that the highest translation efficiencies were found in abundant mRNA. Despite the differences found between mouse (NIH3T3) and human (Jurkat) cells, both cell types share a common translatome composed by ∼800-900 mRNA that encode proteins involved in basic cellular functions. Upon stress, an extensive remodeling in translatomes was observed so that translation of ∼50% of mRNA was inhibited in both cell types, this effect being more dramatic for those mRNA that accounted for most of the cell translation. Interestingly, we found two subsets comprising 1000-1500 mRNA whose translation resisted or was induced by stress. Translation arrest resistant class includes many mRNA encoding aminoacyl tRNA synthetases, ATPases and enzymes involved in DNA replication and stress response such as BiP. This class of mRNA is characterized by high translation rates in both control and stress conditions. Translation inducible class includes mRNA whose translation was relieved after stress, showing a high enrichment in early response transcription factors of bZIP and zinc finger C2H2 classes. Unlike yeast, a general coordination between changes in translation and transcription upon stress (potentiation) was not observed in mammalian cells. Among the different features of mRNA analyzed, we found a relevant association of translation efficiency with the presence of upstream ATG in the 5'UTR and with the length of coding sequence of mRNA, and a looser association with other parameters such as the length and the G+C content of 5'UTR. A model for translatome remodeling during the acute phase of stress response in mammalian cells is proposed.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">5</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/22574127?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Koziol, Agnieszka</style></author><author><style face="normal" font="default" size="100%">Gonzalo, Pilar</style></author><author><style face="normal" font="default" size="100%">Mota, Alba</style></author><author><style face="normal" font="default" size="100%">Pollán, Angela</style></author><author><style face="normal" font="default" size="100%">Lorenzo, Cristina</style></author><author><style face="normal" font="default" size="100%">Colomé, Nuria</style></author><author><style face="normal" font="default" size="100%">Montaner, David</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author><author><style face="normal" font="default" size="100%">Arribas, Joaquín</style></author><author><style face="normal" font="default" size="100%">Canals, Francesc</style></author><author><style face="normal" font="default" size="100%">Arroyo, Alicia G</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">The protease MT1-MMP drives a combinatorial proteolytic program in activated endothelial cells.</style></title><secondary-title><style face="normal" font="default" size="100%">FASEB J</style></secondary-title><alt-title><style face="normal" font="default" size="100%">FASEB J</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Blotting, Western</style></keyword><keyword><style  face="normal" font="default" size="100%">Combinatorial Chemistry Techniques</style></keyword><keyword><style  face="normal" font="default" size="100%">Computational Biology</style></keyword><keyword><style  face="normal" font="default" size="100%">Endothelial Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression Regulation, Enzymologic</style></keyword><keyword><style  face="normal" font="default" size="100%">Inflammation</style></keyword><keyword><style  face="normal" font="default" size="100%">Matrix Metalloproteinase 14</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Protein Array Analysis</style></keyword><keyword><style  face="normal" font="default" size="100%">Reverse Transcriptase Polymerase Chain Reaction</style></keyword><keyword><style  face="normal" font="default" size="100%">RNA Interference</style></keyword><keyword><style  face="normal" font="default" size="100%">RNA, Small Interfering</style></keyword><keyword><style  face="normal" font="default" size="100%">Transcriptome</style></keyword><keyword><style  face="normal" font="default" size="100%">Tumor Necrosis Factor-alpha</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2012</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2012 Nov</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">26</style></volume><pages><style face="normal" font="default" size="100%">4481-94</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;The mechanism by which proteolytic events translate into biological responses is not well understood. To explore the link of pericellular proteolysis to events relevant to capillary sprouting within the inflammatory context, we aimed at the identification of the collection of substrates of the protease MT1-MMP in endothelial tip cells induced by inflammatory stimuli. We applied quantitative proteomics to endothelial cells (ECs) derived from wild-type and MT1-MMP-null mice to identify the substrate repertoire of this protease in TNF-α-activated ECs. Bioinformatics analysis revealed a combinatorial MT1-MMP proteolytic program, in which combined rather than single substrate processing would determine biological decisions by activated ECs, including chemotaxis, cell motility and adhesion, and vasculature development. MT1-MMP-deficient ECs inefficiently processed several of these substrates (TSP1, CYR61, NID1, and SEM3C), validating the model. This novel concept of MT1-MMP-driven combinatorial proteolysis in angiogenesis might be extendable to proteolytic actions in other cellular contexts.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">11</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/22859368?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Vivas, Yurena</style></author><author><style face="normal" font="default" size="100%">Martinez-Garcia, Cristina</style></author><author><style face="normal" font="default" size="100%">Izquierdo, Adriana</style></author><author><style face="normal" font="default" size="100%">Garcia-Garcia, Francisco</style></author><author><style face="normal" font="default" size="100%">Callejas, Sergio</style></author><author><style face="normal" font="default" size="100%">Velasco, Ismael</style></author><author><style face="normal" font="default" size="100%">Campbell, Mark</style></author><author><style face="normal" font="default" size="100%">Ros, Manuel</style></author><author><style face="normal" font="default" size="100%">Dopazo, Ana</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author><author><style face="normal" font="default" size="100%">Vidal-Puig, Antonio</style></author><author><style face="normal" font="default" size="100%">Medina-Gomez, Gema</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Early peroxisome proliferator-activated receptor gamma regulated genes involved in expansion of pancreatic beta cell mass.</style></title><secondary-title><style face="normal" font="default" size="100%">BMC Med Genomics</style></secondary-title><alt-title><style face="normal" font="default" size="100%">BMC Med Genomics</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Proliferation</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Survival</style></keyword><keyword><style  face="normal" font="default" size="100%">Cholesterol</style></keyword><keyword><style  face="normal" font="default" size="100%">Down-Regulation</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression Regulation</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Knockout Techniques</style></keyword><keyword><style  face="normal" font="default" size="100%">Insulin Resistance</style></keyword><keyword><style  face="normal" font="default" size="100%">Insulin-Secreting Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">obesity</style></keyword><keyword><style  face="normal" font="default" size="100%">Oxidation-Reduction</style></keyword><keyword><style  face="normal" font="default" size="100%">Phosphorylation</style></keyword><keyword><style  face="normal" font="default" size="100%">PPAR gamma</style></keyword><keyword><style  face="normal" font="default" size="100%">Signal Transduction</style></keyword><keyword><style  face="normal" font="default" size="100%">Transcription, Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">Transforming Growth Factor beta</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2011</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2011 Dec 30</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">4</style></volume><pages><style face="normal" font="default" size="100%">86</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;The progression towards type 2 diabetes depends on the allostatic response of pancreatic beta cells to synthesise and secrete enough insulin to compensate for insulin resistance. The endocrine pancreas is a plastic tissue able to expand or regress in response to the requirements imposed by physiological and pathophysiological states associated to insulin resistance such as pregnancy, obesity or ageing, but the mechanisms mediating beta cell mass expansion in these scenarios are not well defined. We have recently shown that ob/ob mice with genetic ablation of PPARγ2, a mouse model known as the POKO mouse failed to expand its beta cell mass. This phenotype contrasted with the appropriate expansion of the beta cell mass observed in their obese littermate ob/ob mice. Thus, comparison of these models islets particularly at early ages could provide some new insights on early PPARγ dependent transcriptional responses involved in the process of beta cell mass expansion&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;Here we have investigated PPARγ dependent transcriptional responses occurring during the early stages of beta cell adaptation to insulin resistance in wild type, ob/ob, PPARγ2 KO and POKO mice. We have identified genes known to regulate both the rate of proliferation and the survival signals of beta cells. Moreover we have also identified new pathways induced in ob/ob islets that remained unchanged in POKO islets, suggesting an important role for PPARγ in maintenance/activation of mechanisms essential for the continued function of the beta cell.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;Our data suggest that the expansion of beta cell mass observed in ob/ob islets is associated with the activation of an immune response that fails to occur in POKO islets. We have also indentified other PPARγ dependent differentially regulated pathways including cholesterol biosynthesis, apoptosis through TGF-β signaling and decreased oxidative phosphorylation.&lt;/p&gt;</style></abstract><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/22208362?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Huerta-Cepas, Jaime</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author><author><style face="normal" font="default" size="100%">Huynen, Martijn A</style></author><author><style face="normal" font="default" size="100%">Gabaldón, Toni</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Evidence for short-time divergence and long-time conservation of tissue-specific expression after gene duplication.</style></title><secondary-title><style face="normal" font="default" size="100%">Brief Bioinform</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Brief Bioinform</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Conserved Sequence</style></keyword><keyword><style  face="normal" font="default" size="100%">Evolution, Molecular</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Duplication</style></keyword><keyword><style  face="normal" font="default" size="100%">gene expression</style></keyword><keyword><style  face="normal" font="default" size="100%">Genome</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Organ Specificity</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2011</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2011 Sep</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">12</style></volume><pages><style face="normal" font="default" size="100%">442-8</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Gene duplication is one of the main mechanisms by which genomes can acquire novel functions. It has been proposed that the retention of gene duplicates can be associated to processes of tissue expression divergence. These models predict that acquisition of divergent expression patterns should be acquired shortly after the duplication, and that larger divergence in tissue expression would be expected for paralogs, as compared to orthologs of a similar age. Many studies have shown that gene duplicates tend to have divergent expression patterns and that gene family expansions are associated with high levels of tissue specificity. However, the timeframe in which these processes occur have rarely been investigated in detail, particularly in vertebrates, and most analyses do not include direct comparisons of orthologs as a baseline for the expected levels of tissue specificity in absence of duplications. To assess the specific contribution of duplications to expression divergence, we combine here phylogenetic analyses and expression data from human and mouse. In particular, we study differences in spatial expression among human-mouse paralogs, specifically duplicated after the radiation of mammals, and compare them to pairs of orthologs in the same species. Our results show that gene duplication leads to increased levels of tissue specificity and that this tends to occur promptly after the duplication event.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">5</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/21515902?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Yung, Sun</style></author><author><style face="normal" font="default" size="100%">Ledran, Maria</style></author><author><style face="normal" font="default" size="100%">Moreno-Gimeno, Inmaculada</style></author><author><style face="normal" font="default" size="100%">Conesa, Ana</style></author><author><style face="normal" font="default" size="100%">Montaner, David</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author><author><style face="normal" font="default" size="100%">Dimmick, Ian</style></author><author><style face="normal" font="default" size="100%">Slater, Nicholas J</style></author><author><style face="normal" font="default" size="100%">Marenah, Lamin</style></author><author><style face="normal" font="default" size="100%">Real, Pedro J</style></author><author><style face="normal" font="default" size="100%">Paraskevopoulou, Iliana</style></author><author><style face="normal" font="default" size="100%">Bisbal, Viviana</style></author><author><style face="normal" font="default" size="100%">Burks, Deborah</style></author><author><style face="normal" font="default" size="100%">Santibanez-Koref, Mauro</style></author><author><style face="normal" font="default" size="100%">Moreno, Ruben</style></author><author><style face="normal" font="default" size="100%">Mountford, Joanne</style></author><author><style face="normal" font="default" size="100%">Menendez, Pablo</style></author><author><style face="normal" font="default" size="100%">Armstrong, Lyle</style></author><author><style face="normal" font="default" size="100%">Lako, Majlinda</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Large-scale transcriptional profiling and functional assays reveal important roles for Rho-GTPase signalling and SCL during haematopoietic differentiation of human embryonic stem cells.</style></title><secondary-title><style face="normal" font="default" size="100%">Hum Mol Genet</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Hum Mol Genet</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Acute Disease</style></keyword><keyword><style  face="normal" font="default" size="100%">Anemia, Hemolytic</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Basic Helix-Loop-Helix Transcription Factors</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Differentiation</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Line</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Lineage</style></keyword><keyword><style  face="normal" font="default" size="100%">Cluster Analysis</style></keyword><keyword><style  face="normal" font="default" size="100%">Embryonic Stem Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Erythroid Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Flow Cytometry</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression Profiling</style></keyword><keyword><style  face="normal" font="default" size="100%">Hematopoietic Stem Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Myeloid Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Paracrine Communication</style></keyword><keyword><style  face="normal" font="default" size="100%">Proto-Oncogene Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Reverse Transcriptase Polymerase Chain Reaction</style></keyword><keyword><style  face="normal" font="default" size="100%">rho GTP-Binding Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Signal Transduction</style></keyword><keyword><style  face="normal" font="default" size="100%">Stem Cell Transplantation</style></keyword><keyword><style  face="normal" font="default" size="100%">T-Cell Acute Lymphocytic Leukemia Protein 1</style></keyword><keyword><style  face="normal" font="default" size="100%">Transcriptome</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2011</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2011 Dec 15</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">20</style></volume><pages><style face="normal" font="default" size="100%">4932-46</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Understanding the transcriptional cues that direct differentiation of human embryonic stem cells (hESCs) and human-induced pluripotent stem cells to defined and functional cell types is essential for future clinical applications. In this study, we have compared transcriptional profiles of haematopoietic progenitors derived from hESCs at various developmental stages of a feeder- and serum-free differentiation method and show that the largest transcriptional changes occur during the first 4 days of differentiation. Data mining on the basis of molecular function revealed Rho-GTPase signalling as a key regulator of differentiation. Inhibition of this pathway resulted in a significant reduction in the numbers of emerging haematopoietic progenitors throughout the differentiation window, thereby uncovering a previously unappreciated role for Rho-GTPase signalling during human haematopoietic development. Our analysis indicated that SCL was the 11th most upregulated transcript during the first 4 days of the hESC differentiation process. Overexpression of SCL in hESCs promoted differentiation to meso-endodermal lineages, the emergence of haematopoietic and erythro-megakaryocytic progenitors and accelerated erythroid differentiation. Importantly, intrasplenic transplantation of SCL-overexpressing hESC-derived haematopoietic cells enhanced recovery from induced acute anaemia without significant cell engraftment, suggesting a paracrine-mediated effect.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">24</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/21937587?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Reumers, Joke</style></author><author><style face="normal" font="default" size="100%">Conde, Lucia</style></author><author><style face="normal" font="default" size="100%">Medina, Ignacio</style></author><author><style face="normal" font="default" size="100%">Maurer-Stroh, Sebastian</style></author><author><style face="normal" font="default" size="100%">Van Durme, Joost</style></author><author><style face="normal" font="default" size="100%">Dopazo, Joaquin</style></author><author><style face="normal" font="default" size="100%">Rousseau, Frederic</style></author><author><style face="normal" font="default" size="100%">Schymkowitz, Joost</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Joint annotation of coding and non-coding single nucleotide polymorphisms and mutations in the SNPeffect and PupaSuite databases.</style></title><secondary-title><style face="normal" font="default" size="100%">Nucleic Acids Res</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Nucleic Acids Res</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Amino Acid Substitution</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Databases, Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Diseases, Inborn</style></keyword><keyword><style  face="normal" font="default" size="100%">HSP70 Heat-Shock Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Internet</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">MicroRNAs</style></keyword><keyword><style  face="normal" font="default" size="100%">mutation</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Single Nucleotide</style></keyword><keyword><style  face="normal" font="default" size="100%">Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Rats</style></keyword><keyword><style  face="normal" font="default" size="100%">RNA Splice Sites</style></keyword><keyword><style  face="normal" font="default" size="100%">Transcription Factors</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2008</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2008 Jan</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">36</style></volume><pages><style face="normal" font="default" size="100%">D825-9</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Single nucleotide polymorphisms (SNPs) are, together with copy number variation, the primary source of variation in the human genome. SNPs are associated with altered response to drug treatment, susceptibility to disease and other phenotypic variation. Furthermore, during genetic screens for disease-associated mutations in groups of patients and control individuals, the distinction between disease causing mutation and polymorphism is often unclear. Annotation of the functional and structural implications of single nucleotide changes thus provides valuable information to interpret and guide experiments. The SNPeffect and PupaSuite databases are now synchronized to deliver annotations for both non-coding and coding SNP, as well as annotations for the SwissProt set of human disease mutations. In addition, SNPeffect now contains predictions of Tango2: an improved aggregation detector, and Waltz: a novel predictor of amyloid-forming sequences, as well as improved predictors for regions that are recognized by the Hsp70 family of chaperones. The new PupaSuite version incorporates predictions for SNPs in silencers and miRNAs including their targets, as well as additional methods for predicting SNPs in TFBSs and splice sites. Also predictions for mouse and rat genomes have been added. In addition, a PupaSuite web service has been developed to enable data access, programmatically. The combined database holds annotations for 4,965,073 regulatory as well as 133,505 coding human SNPs and 14,935 disease mutations, and phenotypic descriptions of 43,797 human proteins and is accessible via http://snpeffect.vib.be and http://pupasuite.bioinfo.cipf.es/.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">Database issue</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/18086700?dopt=Abstract</style></custom1></record></records></xml>