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José Luis Lavín Trueba, received two B.Sc, in Biology (1999) and Biochemistry (2000) from the University of Salamanca. For his Ph.D.studies he became interested in bioinformatics and received his Ph.D. on this discipline at the Dept. of Genetics and Microbiology at the Public University of Navarre in 2008 (awarded with the extraordinary PhD. prize). He worked in different fields of that discipline (Comparative Genomics, Genome Annotation, Promoter sequences analysis and Secreted proteins analysis). During his studies he also became proficient in some programming languages such as Perl/CGI, MySQL, HTML/CSS or R, which allowed him to develop online biological databases and simple bioinformatic tools (such as parsers and comparative genomics pipelines) that greatly enhanced the kind of analysis he performed for his research. As result of this work in bioinformatics he has been included in various research projects and collaborated as gene annotator for a number of fungal genome sequencing projects with the Joint Genome Institute (Department of Energy - U.S.). He has authored several presentations in Congress and Workshops and published his work in different high impact peer-reviewed journals (e.g. BMC Genomics, Veterinary Microbiology, PNAS, Database, Mitochondrion, Journal of Immunology, Gastroenterology, Hepatology, Current Biology, Science Advances or Science). He shifted to the Next Generation Sequencing field in 2012 and specialized on improving data management/processing
The aim of this trial was to assess the effect of feeding a concentrate including cold-pressed rapeseed cake (CPRC) on productive performance, milk quality and its sensory properties, ruminal biohydrogenation, and bacterial communities. Eighteen cows were paired, and two experimental diets (control vs. CPRC) were distributed within the pair. Concentrates were iso-energetic and iso-proteic and contained similar amounts of fat. The average days in milk, milk yield, and body weight of the animals were (mean ± SD) 172 ± 112 d, 585 ± 26 kg, and 25.4 ± 6.2 kg/d, respectively. The experiment lasted for 10 wk. Feeding CPRC resulted in lower ruminal saturated (p < 0.001) and higher monounsaturated (p = 0.002) fatty acids. Feeding CPRC increased Ruminococcus, Prevotella, and Entodinium but decreased Blautia; p-75-a5; undefined genera within orders Clostridiaceae and RF39 and within families Christensenellaceae, Lachnospiracease, and Ruminococcaceae; and fungi from the phylum neocallimastigomycota. The milk fatty acid profile was characterized by a lower n6:n3 ratio (p = 0.028). Feeding CPRC did not affect the milk yield, milk quality, or fat corrected milk (p > 0.05). Feeding CPRC improved the overall milk acceptability (p = 0.047). In conclusion, CPRC affected some microbial taxa, modified the biohydrogenation process, and improved the milk fatty acid profile and consumer acceptance without detrimental effects on milk production and composition.
Idoia Goiri; Izaro Zubiria; Jose Luís Lavín; Hanen Benhissi; Raquel Atxaerandio; Roberto Ruiz; Nerea Mandaluniz; Aser García-Rodríguez. Evaluating the Inclusion of Cold-Pressed Rapeseed Cake in the Concentrate for Dairy Cows upon Ruminal Biohydrogenation Process, Ruminal Microbial Community and Milk Production and Acceptability. Animals 2021, 11, 2553 .
AMA StyleIdoia Goiri, Izaro Zubiria, Jose Luís Lavín, Hanen Benhissi, Raquel Atxaerandio, Roberto Ruiz, Nerea Mandaluniz, Aser García-Rodríguez. Evaluating the Inclusion of Cold-Pressed Rapeseed Cake in the Concentrate for Dairy Cows upon Ruminal Biohydrogenation Process, Ruminal Microbial Community and Milk Production and Acceptability. Animals. 2021; 11 (9):2553.
Chicago/Turabian StyleIdoia Goiri; Izaro Zubiria; Jose Luís Lavín; Hanen Benhissi; Raquel Atxaerandio; Roberto Ruiz; Nerea Mandaluniz; Aser García-Rodríguez. 2021. "Evaluating the Inclusion of Cold-Pressed Rapeseed Cake in the Concentrate for Dairy Cows upon Ruminal Biohydrogenation Process, Ruminal Microbial Community and Milk Production and Acceptability." Animals 11, no. 9: 2553.
While a structural description of the molecular mechanisms guiding ribosome assembly in eukaryotic systems is emerging, bacteria use an unrelated core set of assembly factors for which high-resolution structural information is still missing. To address this, we used single-particle cryo–electron microscopy to visualize the effects of bacterial ribosome assembly factors RimP, RbfA, RsmA, and RsgA on the conformational landscape of the 30S ribosomal subunit and obtained eight snapshots representing late steps in the folding of the decoding center. Analysis of these structures identifies a conserved secondary structure switch in the 16S ribosomal RNA central to decoding site maturation and suggests both a sequential order of action and molecular mechanisms for the assembly factors in coordinating and controlling this switch. Structural and mechanistic parallels between bacterial and eukaryotic systems indicate common folding features inherent to all ribosomes.
Andreas Schedlbauer; Idoia Iturrioz; Borja Ochoa-Lizarralde; Tammo Diercks; Jorge Pedro López-Alonso; José Luis Lavin; Tatsuya Kaminishi; Retina Çapuni; Neha Dhimole; Elisa de Astigarraga; David Gil-Carton; Paola Fucini; Sean R. Connell. A conserved rRNA switch is central to decoding site maturation on the small ribosomal subunit. Science Advances 2021, 7, eabf7547 .
AMA StyleAndreas Schedlbauer, Idoia Iturrioz, Borja Ochoa-Lizarralde, Tammo Diercks, Jorge Pedro López-Alonso, José Luis Lavin, Tatsuya Kaminishi, Retina Çapuni, Neha Dhimole, Elisa de Astigarraga, David Gil-Carton, Paola Fucini, Sean R. Connell. A conserved rRNA switch is central to decoding site maturation on the small ribosomal subunit. Science Advances. 2021; 7 (23):eabf7547.
Chicago/Turabian StyleAndreas Schedlbauer; Idoia Iturrioz; Borja Ochoa-Lizarralde; Tammo Diercks; Jorge Pedro López-Alonso; José Luis Lavin; Tatsuya Kaminishi; Retina Çapuni; Neha Dhimole; Elisa de Astigarraga; David Gil-Carton; Paola Fucini; Sean R. Connell. 2021. "A conserved rRNA switch is central to decoding site maturation on the small ribosomal subunit." Science Advances 7, no. 23: eabf7547.
Lyme carditis is an extracutaneous manifestation of Lyme disease characterized by episodes of atrioventricular block of varying degrees and additional, less reported cardiomyopathies. The molecular changes associated with the response to Borrelia burgdorferi over the course of infection are poorly understood. Here, we identify broad transcriptomic and proteomic changes in the heart during infection that reveal a profound down-regulation of mitochondrial components. We also describe the long-term functional modulation of macrophages exposed to live bacteria, characterized by an augmented glycolytic output, increased spirochetal binding and internalization, and reduced inflammatory responses. In vitro, glycolysis inhibition reduces the production of tumor necrosis factor (TNF) by memory macrophages, whereas in vivo, it produces the reversion of the memory phenotype, the recovery of tissue mitochondrial components, and decreased inflammation and spirochetal burdens. These results show that B. burgdorferi induces long-term, memory-like responses in macrophages with tissue-wide consequences that are amenable to be manipulated in vivo.
Diego Barriales; Itziar Martín-Ruiz; Ana Carreras-González; Marta Montesinos-Robledo; Mikel Azkargorta; Ibon Iloro; Iraide Escobés; Teresa Martín-Mateos; Estibaliz Atondo; Ainhoa Palacios; Monika Gonzalez-Lopez; Laura Bárcena; Ana R. Cortázar; Diana Cabrera; Ainize Peña-Cearra; Sebastiaan M. van Liempd; Juan M. Falcón-Pérez; Miguel A. Pascual-Itoiz; Juana María Flores; Leticia Abecia; Aize Pellon; Maria Luz Martínez-Chantar; Ana M. Aransay; Alberto Pascual; Felix Elortza; Edurne Berra; José Luis Lavín; Héctor Rodríguez; Juan Anguita. Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart. PLOS Biology 2021, 19, e3001062 .
AMA StyleDiego Barriales, Itziar Martín-Ruiz, Ana Carreras-González, Marta Montesinos-Robledo, Mikel Azkargorta, Ibon Iloro, Iraide Escobés, Teresa Martín-Mateos, Estibaliz Atondo, Ainhoa Palacios, Monika Gonzalez-Lopez, Laura Bárcena, Ana R. Cortázar, Diana Cabrera, Ainize Peña-Cearra, Sebastiaan M. van Liempd, Juan M. Falcón-Pérez, Miguel A. Pascual-Itoiz, Juana María Flores, Leticia Abecia, Aize Pellon, Maria Luz Martínez-Chantar, Ana M. Aransay, Alberto Pascual, Felix Elortza, Edurne Berra, José Luis Lavín, Héctor Rodríguez, Juan Anguita. Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart. PLOS Biology. 2021; 19 (1):e3001062.
Chicago/Turabian StyleDiego Barriales; Itziar Martín-Ruiz; Ana Carreras-González; Marta Montesinos-Robledo; Mikel Azkargorta; Ibon Iloro; Iraide Escobés; Teresa Martín-Mateos; Estibaliz Atondo; Ainhoa Palacios; Monika Gonzalez-Lopez; Laura Bárcena; Ana R. Cortázar; Diana Cabrera; Ainize Peña-Cearra; Sebastiaan M. van Liempd; Juan M. Falcón-Pérez; Miguel A. Pascual-Itoiz; Juana María Flores; Leticia Abecia; Aize Pellon; Maria Luz Martínez-Chantar; Ana M. Aransay; Alberto Pascual; Felix Elortza; Edurne Berra; José Luis Lavín; Héctor Rodríguez; Juan Anguita. 2021. "Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart." PLOS Biology 19, no. 1: e3001062.
Colorectal cancer pathogenesis and progression is associated with the presence of Fusobacterium nucleatum and the reduction of acetylated derivatives of spermidine, as well as dietary components such as tannin‐rich foods. We show that a new tannase orthologue of F. nucleatum (TanBFnn) has significant structural differences with its Lactobacillus plantarum counterpart affecting the flap covering the active site and the accessibility of substrates. Crystallographic and molecular dynamics analysis revealed binding of polyamines to a small cavity that connects the active site with the bulk solvent which interact with catalytically indispensable residues. As a result, spermidine and its derivatives, particularly N8‐acetylated spermidine, inhibit the hydrolytic activity of TanBFnn and increase the toxicity of gallotannins to F. nucleatum. Our results support a model in which the balance between the detoxicant activity of TanBFnn and the presence of metabolic inhibitors can dictate either conducive or unfavourable conditions for the survival of F. nucleatum.
José Miguel Mancheño; Estíbaliz Atondo; Julen Tomás‐Cortázar; José Luís Lavín; Laura Plaza‐Vinuesa; Itziar Martín‐Ruiz; Diego Barriales; Ainhoa Palacios; Claudio Daniel Navo; Leticia Sampedro; Ainize Peña‐Cearra; Miguel Ángel Pascual‐Itoiz; Janire Castelo; Ana Carreras‐González; Donatello Castellana; Aize Pellón; Susana Delgado; Patricia Ruas‐Madiedo; Blanca De Las Rivas; Leticia Abecia; Rosario Muñoz; Gonzalo Jiménez‐Osés; Juan Anguita; Héctor Rodríguez. A structurally unique Fusobacterium nucleatum tannase provides detoxicant activity against gallotannins and pathogen resistance. Microbial Biotechnology 2020, 1 .
AMA StyleJosé Miguel Mancheño, Estíbaliz Atondo, Julen Tomás‐Cortázar, José Luís Lavín, Laura Plaza‐Vinuesa, Itziar Martín‐Ruiz, Diego Barriales, Ainhoa Palacios, Claudio Daniel Navo, Leticia Sampedro, Ainize Peña‐Cearra, Miguel Ángel Pascual‐Itoiz, Janire Castelo, Ana Carreras‐González, Donatello Castellana, Aize Pellón, Susana Delgado, Patricia Ruas‐Madiedo, Blanca De Las Rivas, Leticia Abecia, Rosario Muñoz, Gonzalo Jiménez‐Osés, Juan Anguita, Héctor Rodríguez. A structurally unique Fusobacterium nucleatum tannase provides detoxicant activity against gallotannins and pathogen resistance. Microbial Biotechnology. 2020; ():1.
Chicago/Turabian StyleJosé Miguel Mancheño; Estíbaliz Atondo; Julen Tomás‐Cortázar; José Luís Lavín; Laura Plaza‐Vinuesa; Itziar Martín‐Ruiz; Diego Barriales; Ainhoa Palacios; Claudio Daniel Navo; Leticia Sampedro; Ainize Peña‐Cearra; Miguel Ángel Pascual‐Itoiz; Janire Castelo; Ana Carreras‐González; Donatello Castellana; Aize Pellón; Susana Delgado; Patricia Ruas‐Madiedo; Blanca De Las Rivas; Leticia Abecia; Rosario Muñoz; Gonzalo Jiménez‐Osés; Juan Anguita; Héctor Rodríguez. 2020. "A structurally unique Fusobacterium nucleatum tannase provides detoxicant activity against gallotannins and pathogen resistance." Microbial Biotechnology , no. : 1.
Antimicrobial and antioxidant properties of spent coffee grounds (SCG) make them a potential ingredient in a diet for ruminants. This study investigated the effects of SCG on rumen microbiota. For 51 days, 36 dairy ewes were assigned to the experimental treatments (0, 30, 50, and 100 g SCG/kg). Ruminal samples were collected on day 50. DNA was extracted and subjected to paired-end Illumina sequencing of the V3-V4 hypervariable region of the 16S rRNA genes. Bioinformatic analyses were performed using QIIME (v.1.9.0). SCG increased dose-dependently bacterial diversity and altered bacterial structure. Further, 60, 78, and 449 operational taxonomic unit (OUT) were different between control and 30, 50 and 100 g/kg SCG groups, respectively. Higher differences were observed between the control and 100 g/kg SCG group, where OTU of the genera Treponema, CF231, Butyrivibrio, BF331, Anaeroplasma, Blautia, Fibrobacter, and Clostridium were enriched with SCG. Correlations between volatile fatty acids (VFA) and bacterial taxa were sparser in the SCG groups and had little overlap. Certain bacterial taxa presented different signs of the correlation with VFA in SCG and control groups, but Butyrivibrio and Blautia consistently correlated with branched-chain VFA in all groups. SCG induced shifts in the ruminal bacterial community and altered the correlation networks among bacterial taxa and ruminal VFA.
Idoia Goiri; Xabier Díaz De Otálora; Roberto Ruiz; Jagoba Rey; Raquel Atxaerandio; Jose Luis Lavín; David San Martin; Mikel Orive; Bruno Iñarra; Jaime Zufia; Jabi Urkiza; Aser García-Rodríguez. Spent Coffee Grounds Alter Bacterial Communities in Latxa Dairy Ewes. Microorganisms 2020, 8, 1961 .
AMA StyleIdoia Goiri, Xabier Díaz De Otálora, Roberto Ruiz, Jagoba Rey, Raquel Atxaerandio, Jose Luis Lavín, David San Martin, Mikel Orive, Bruno Iñarra, Jaime Zufia, Jabi Urkiza, Aser García-Rodríguez. Spent Coffee Grounds Alter Bacterial Communities in Latxa Dairy Ewes. Microorganisms. 2020; 8 (12):1961.
Chicago/Turabian StyleIdoia Goiri; Xabier Díaz De Otálora; Roberto Ruiz; Jagoba Rey; Raquel Atxaerandio; Jose Luis Lavín; David San Martin; Mikel Orive; Bruno Iñarra; Jaime Zufia; Jabi Urkiza; Aser García-Rodríguez. 2020. "Spent Coffee Grounds Alter Bacterial Communities in Latxa Dairy Ewes." Microorganisms 8, no. 12: 1961.
Helicobacter pylori infects 4.4 billion individuals worldwide and is considered the most important etiologic agent for peptic ulcers and gastric cancer. Individual response to H. pylori infection is complex and depends on complex interactions between host and environmental factors. The pathway towards gastric cancer is a sequence of events known as Correa’s model of gastric carcinogenesis, a stepwise inflammatory process from normal mucosa to chronic-active gastritis, atrophy, metaplasia and gastric adenocarcinoma. This study examines gastric clinical specimens representing different steps of the Correa pathway with the aim of identifying the expression profiles of coding- and non-coding RNAs that may have a role in Correa’s model of gastric carcinogenesis. We screened for differentially expressed genes in gastric biopsies by employing RNAseq, microarrays and qRT-PCR. Here we provide a detailed description of the experiments, methods and results generated. The datasets may help other scientists and clinicians to find new clues to the pathogenesis of H. pylori and the mechanisms of progression of the infection to more severe gastric diseases. Data is available via ArrayExpress.
Sergio Lario; María J. Ramírez-Lázaro; Aintzane González-Lahera; José Luis Lavín; Maria Vila-Casadesús; María E. Quílez; Anna Brunet-Vega; Juan J. Lozano; Ana M. Aransay; Xavier Calvet. Cross-sectional study of human coding- and non-coding RNAs in progressive stages of Helicobacter pylori infection. Scientific Data 2020, 7, 1 -9.
AMA StyleSergio Lario, María J. Ramírez-Lázaro, Aintzane González-Lahera, José Luis Lavín, Maria Vila-Casadesús, María E. Quílez, Anna Brunet-Vega, Juan J. Lozano, Ana M. Aransay, Xavier Calvet. Cross-sectional study of human coding- and non-coding RNAs in progressive stages of Helicobacter pylori infection. Scientific Data. 2020; 7 (1):1-9.
Chicago/Turabian StyleSergio Lario; María J. Ramírez-Lázaro; Aintzane González-Lahera; José Luis Lavín; Maria Vila-Casadesús; María E. Quílez; Anna Brunet-Vega; Juan J. Lozano; Ana M. Aransay; Xavier Calvet. 2020. "Cross-sectional study of human coding- and non-coding RNAs in progressive stages of Helicobacter pylori infection." Scientific Data 7, no. 1: 1-9.
Secretome represents a main target for understanding the mechanisms of fungal adaptation. In the present study, we focus on the secretomes of fungi associated with infections in humans and other mammals in order to explore relationships between the diverse morphological and phylogenetic groups. Almost all the mammalian pathogenic fungi analyzed have secretome sizes smaller than 1000 proteins and, secreted proteins comprise between 5% and 10% of the total proteome. As expected, the correlation pattern between the secretome size and the total proteome was similar to that described in previous secretome studies of fungi. With regard to the morphological groups, minimum secretome sizes of less than 250 secreted proteins and low values for the fraction of secreted proteins are shown in mammalian pathogenic fungi with reduced proteomes such as microsporidia, atypical fungi and some species of yeasts and yeast-like fungi (Malassezia). On the other hand, filamentous fungi have significantly more secreted proteins and the highest numbers are present in species of filamentous fungi that also are plant or insect pathogens (Fusarium verticilloides, Fusarium oxysporum and Basidiobolus meristosporus). With respect to phylogeny, there are also variations in secretome size across fungal subphyla: Microsporidia, Taphrinomycotina, Ustilagomycotina and Saccharomycotina contain small secretomes; whereas larger secretomes are found in Agaricomycotina, Pezizomycotina, Mucoromycotina and Entomophthoromycotina. Finally, principal component analysis (PCA) was conducted on the complete secretomes. The PCA results revealed that, in general, secretomes of fungi belonging to the same morphological group or subphyla cluster together. In conclusion, our results point out that in medically important fungi there is a relationship between the secretome and the morphological group or phylogenetic classification.
Sarai Varona; José Luis Lavín; José A. Oguiza. Secretomes of medically important fungi reflect morphological and phylogenetic diversity. Fungal Biology 2020, 124, 915 -923.
AMA StyleSarai Varona, José Luis Lavín, José A. Oguiza. Secretomes of medically important fungi reflect morphological and phylogenetic diversity. Fungal Biology. 2020; 124 (11):915-923.
Chicago/Turabian StyleSarai Varona; José Luis Lavín; José A. Oguiza. 2020. "Secretomes of medically important fungi reflect morphological and phylogenetic diversity." Fungal Biology 124, no. 11: 915-923.
We report here the draft genome sequence of an extended-spectrum β-lactamase (ESBL)-producing Escherichia species isolated from rectal feces collected from beef cattle in northern Spain. Analysis of the draft genome identified the strain as a member of the newly described species Escherichia marmotae .
Medelin Ocejo; Maitane Tello; Beatriz Oporto; José Luis Lavín; Ana Hurtado. Draft Genome Sequence of Escherichia marmotae E690, Isolated from Beef Cattle. Microbiology Resource Announcements 2020, 9, 1 .
AMA StyleMedelin Ocejo, Maitane Tello, Beatriz Oporto, José Luis Lavín, Ana Hurtado. Draft Genome Sequence of Escherichia marmotae E690, Isolated from Beef Cattle. Microbiology Resource Announcements. 2020; 9 (32):1.
Chicago/Turabian StyleMedelin Ocejo; Maitane Tello; Beatriz Oporto; José Luis Lavín; Ana Hurtado. 2020. "Draft Genome Sequence of Escherichia marmotae E690, Isolated from Beef Cattle." Microbiology Resource Announcements 9, no. 32: 1.
Cancer cells can develop a strong addiction to discrete molecular regulators, which control the aberrant gene expression programs that drive and maintain the cancer phenotype. Here, we report the identification of the RNA-binding protein HuR/ELAVL1 as a central oncogenic driver for malignant peripheral nerve sheath tumors (MPNSTs), which are highly aggressive sarcomas that originate from cells of the Schwann cell lineage. HuR was found to be highly elevated and bound to a multitude of cancer-associated transcripts in human MPNST samples. Accordingly, genetic and pharmacological inhibition of HuR had potent cytostatic and cytotoxic effects on tumor growth, and strongly suppressed metastatic capacity in vivo. Importantly, we linked the profound tumorigenic function of HuR to its ability to simultaneously regulate multiple essential oncogenic pathways in MPNST cells, including the Wnt/β-catenin, YAP/TAZ, RB/E2F, and BET pathways, which converge on key transcriptional networks. Given the exceptional dependency of MPNST cells on HuR for survival, proliferation, and dissemination, we propose that HuR represents a promising therapeutic target for MPNST treatment.
Marta Palomo-Irigoyen; Encarnación Pérez-Andrés; Marta Iruarrizaga-Lejarreta; Adrián Barreira-Manrique; Miguel Tamayo-Caro; Laura Vila-Vecilla; Leire Moreno-Cugnon; Nagore Beitia; Daniela Medrano; David Fernández-Ramos; Juan José Lozano; Satoshi Okawa; José Luis Lavín; Natalia Martín-Martín; James D. Sutherland; Virginia Guitiérez De Juan; Monika Gonzalez-Lopez; Nuria Macías-Cámara; David Mosén-Ansorena; Liyam Laraba; C. Oliver Hanemann; Emanuela Ercolano; David B. Parkinson; Christopher W. Schultz; Marcos J. Araúzo-Bravo; Alex M. Ascensión; Daniela Gerovska; Haizea Iribar; Ander Izeta; Peter Pytel; Philipp Krastel; Alessandro Provenzani; Pierfausto Seneci; Ruben D. Carrasco; Antonio Del Sol; María Luz Martinez-Chantar; Rosa Barrio; Eduard Serra; Conxi Lazaro; Adrienne M. Flanagan; Myriam Gorospe; Nancy Ratner; Ana María Aransay; Arkaitz Carracedo; Marta Varela-Rey; Ashwin Woodhoo. HuR/ELAVL1 drives malignant peripheral nerve sheath tumor growth and metastasis. Journal of Clinical Investigation 2020, 130, 3848 -3864.
AMA StyleMarta Palomo-Irigoyen, Encarnación Pérez-Andrés, Marta Iruarrizaga-Lejarreta, Adrián Barreira-Manrique, Miguel Tamayo-Caro, Laura Vila-Vecilla, Leire Moreno-Cugnon, Nagore Beitia, Daniela Medrano, David Fernández-Ramos, Juan José Lozano, Satoshi Okawa, José Luis Lavín, Natalia Martín-Martín, James D. Sutherland, Virginia Guitiérez De Juan, Monika Gonzalez-Lopez, Nuria Macías-Cámara, David Mosén-Ansorena, Liyam Laraba, C. Oliver Hanemann, Emanuela Ercolano, David B. Parkinson, Christopher W. Schultz, Marcos J. Araúzo-Bravo, Alex M. Ascensión, Daniela Gerovska, Haizea Iribar, Ander Izeta, Peter Pytel, Philipp Krastel, Alessandro Provenzani, Pierfausto Seneci, Ruben D. Carrasco, Antonio Del Sol, María Luz Martinez-Chantar, Rosa Barrio, Eduard Serra, Conxi Lazaro, Adrienne M. Flanagan, Myriam Gorospe, Nancy Ratner, Ana María Aransay, Arkaitz Carracedo, Marta Varela-Rey, Ashwin Woodhoo. HuR/ELAVL1 drives malignant peripheral nerve sheath tumor growth and metastasis. Journal of Clinical Investigation. 2020; 130 (7):3848-3864.
Chicago/Turabian StyleMarta Palomo-Irigoyen; Encarnación Pérez-Andrés; Marta Iruarrizaga-Lejarreta; Adrián Barreira-Manrique; Miguel Tamayo-Caro; Laura Vila-Vecilla; Leire Moreno-Cugnon; Nagore Beitia; Daniela Medrano; David Fernández-Ramos; Juan José Lozano; Satoshi Okawa; José Luis Lavín; Natalia Martín-Martín; James D. Sutherland; Virginia Guitiérez De Juan; Monika Gonzalez-Lopez; Nuria Macías-Cámara; David Mosén-Ansorena; Liyam Laraba; C. Oliver Hanemann; Emanuela Ercolano; David B. Parkinson; Christopher W. Schultz; Marcos J. Araúzo-Bravo; Alex M. Ascensión; Daniela Gerovska; Haizea Iribar; Ander Izeta; Peter Pytel; Philipp Krastel; Alessandro Provenzani; Pierfausto Seneci; Ruben D. Carrasco; Antonio Del Sol; María Luz Martinez-Chantar; Rosa Barrio; Eduard Serra; Conxi Lazaro; Adrienne M. Flanagan; Myriam Gorospe; Nancy Ratner; Ana María Aransay; Arkaitz Carracedo; Marta Varela-Rey; Ashwin Woodhoo. 2020. "HuR/ELAVL1 drives malignant peripheral nerve sheath tumor growth and metastasis." Journal of Clinical Investigation 130, no. 7: 3848-3864.
Editorial: Macrophage Metabolism and Immune Responses
Héctor Rodríguez; Rafael Prados-Rosales; José Luis Lavín; Massimiliano Mazzone; Juan Anguita. Editorial: Macrophage Metabolism and Immune Responses. Frontiers in Immunology 2020, 11, 1 .
AMA StyleHéctor Rodríguez, Rafael Prados-Rosales, José Luis Lavín, Massimiliano Mazzone, Juan Anguita. Editorial: Macrophage Metabolism and Immune Responses. Frontiers in Immunology. 2020; 11 ():1.
Chicago/Turabian StyleHéctor Rodríguez; Rafael Prados-Rosales; José Luis Lavín; Massimiliano Mazzone; Juan Anguita. 2020. "Editorial: Macrophage Metabolism and Immune Responses." Frontiers in Immunology 11, no. : 1.
: Cholangiocarcinoma (CCA) comprises a group of heterogeneous biliary cancers with dismal prognosis. The etiologies of most CCAs are unknown, but primary sclerosing cholangitis (PSC) is a risk factor. Non-invasive diagnosis of CCA is challenging and accurate biomarkers are lacking. We aimed to characterize the transcriptomic profile of serum and urine extracellular vesicles (EVs) from patients with CCA, PSC, ulcerative colitis (UC), and healthy individuals. Serum and urine EVs were isolated by serial ultracentrifugations and characterized by nanoparticle tracking analysis, transmission electron microscopy, and immunoblotting. EVs transcriptome was determined by Illumina gene expression array [messenger RNAs (mRNA) and non-coding RNAs (ncRNAs)]. Differential RNA profiles were found in serum and urine EVs from patients with CCA compared to control groups (disease and healthy), showing high diagnostic capacity. The comparison of the mRNA profiles of serum or urine EVs from patients with CCA with the transcriptome of tumor tissues from two cohorts of patients, CCA cells in vitro, and CCA cells-derived EVs, identified 105 and 39 commonly-altered transcripts, respectively. Gene ontology analysis indicated that most commonly-altered mRNAs participate in carcinogenic steps. Overall, patients with CCA present specific RNA profiles in EVs mirroring the tumor, and constituting novel promising liquid biopsy biomarkers.
Ainhoa Lapitz; Ander Arbelaiz; Colm J. O’Rourke; Jose L. Lavin; Adelaida La Casta; Cesar Ibarra; Juan P. Jimeno; Alvaro Santos-Laso; Laura Izquierdo-Sanchez; Marcin Krawczyk; Maria J. Perugorria; Raul Jimenez-Aguero; Alberto Sanchez-Campos; Ioana Riaño; Esperanza Gónzalez; Frank Lammert; Marco Marzioni; Rocio I.R. Macias; Jose J. G. Marin; Tom H. Karlsen; Luis Bujanda; Juan M. Falcón-Pérez; Jesper B. Andersen; Ana M. Aransay; Pedro M. Rodrigues; Jesus M. Banales. Patients with Cholangiocarcinoma Present Specific RNA Profiles in Serum and Urine Extracellular Vesicles Mirroring the Tumor Expression: Novel Liquid Biopsy Biomarkers for Disease Diagnosis. Cells 2020, 9, 721 .
AMA StyleAinhoa Lapitz, Ander Arbelaiz, Colm J. O’Rourke, Jose L. Lavin, Adelaida La Casta, Cesar Ibarra, Juan P. Jimeno, Alvaro Santos-Laso, Laura Izquierdo-Sanchez, Marcin Krawczyk, Maria J. Perugorria, Raul Jimenez-Aguero, Alberto Sanchez-Campos, Ioana Riaño, Esperanza Gónzalez, Frank Lammert, Marco Marzioni, Rocio I.R. Macias, Jose J. G. Marin, Tom H. Karlsen, Luis Bujanda, Juan M. Falcón-Pérez, Jesper B. Andersen, Ana M. Aransay, Pedro M. Rodrigues, Jesus M. Banales. Patients with Cholangiocarcinoma Present Specific RNA Profiles in Serum and Urine Extracellular Vesicles Mirroring the Tumor Expression: Novel Liquid Biopsy Biomarkers for Disease Diagnosis. Cells. 2020; 9 (3):721.
Chicago/Turabian StyleAinhoa Lapitz; Ander Arbelaiz; Colm J. O’Rourke; Jose L. Lavin; Adelaida La Casta; Cesar Ibarra; Juan P. Jimeno; Alvaro Santos-Laso; Laura Izquierdo-Sanchez; Marcin Krawczyk; Maria J. Perugorria; Raul Jimenez-Aguero; Alberto Sanchez-Campos; Ioana Riaño; Esperanza Gónzalez; Frank Lammert; Marco Marzioni; Rocio I.R. Macias; Jose J. G. Marin; Tom H. Karlsen; Luis Bujanda; Juan M. Falcón-Pérez; Jesper B. Andersen; Ana M. Aransay; Pedro M. Rodrigues; Jesus M. Banales. 2020. "Patients with Cholangiocarcinoma Present Specific RNA Profiles in Serum and Urine Extracellular Vesicles Mirroring the Tumor Expression: Novel Liquid Biopsy Biomarkers for Disease Diagnosis." Cells 9, no. 3: 721.
Recent evidences indicate that mitochondrial genes and function are decreased in active ulcerative colitis (UC) patients, in particular, the activity of Complex I of the electron transport chain is heavily compromised. MCJ is a mitochondrial inner membrane protein identified as a natural inhibitor of respiratory chain Complex I. The induction of experimental colitis in MCJ-deficient mice leads to the upregulation of Timp3 expression resulting in the inhibition of TACE activity that likely inhibits Tnf and Tnfr1 shedding from the cell membrane in the colon. MCJ-deficient mice also show higher expression of Myd88 and Tlr9, proinflammatory genes and disease severity. Interestingly, the absence of MCJ resulted in distinct microbiota metabolism and composition, including a member of the gut community in UC patients, Ruminococcus gnavus. These changes provoked an effect on IgA levels. Gene expression analyses in UC patients showed decreased levels of MCJ and higher expression of TIMP3, suggesting a relevant role of mitochondrial genes and function among active UC. The MCJ deficiency disturbs the regulatory relationship between the host mitochondria and microbiota affecting disease severity. Our results indicate that mitochondria function may be an important factor in the pathogenesis. All together support the importance of MCJ regulation during UC.
Miguel Angel Pascual-Itoiz; Ainize Peña-Cearra; Itziar Martín-Ruiz; José Luis Lavín; Carolina Simó; Héctor Rodríguez; Estibaliz Atondo; Juana María Flores; Ana Carreras-González; Julen Tomás-Cortázar; Diego Barriales; Ainhoa Palacios; Virginia García-Cañas; Aize Pellón; Asier Fullaondo; Ana Mª Aransay; Rafael Prados-Rosales; Rebeca Martín; Juan Anguita; Leticia Abecia. The mitochondrial negative regulator MCJ modulates the interplay between microbiota and the host during ulcerative colitis. Scientific Reports 2020, 10, 1 -13.
AMA StyleMiguel Angel Pascual-Itoiz, Ainize Peña-Cearra, Itziar Martín-Ruiz, José Luis Lavín, Carolina Simó, Héctor Rodríguez, Estibaliz Atondo, Juana María Flores, Ana Carreras-González, Julen Tomás-Cortázar, Diego Barriales, Ainhoa Palacios, Virginia García-Cañas, Aize Pellón, Asier Fullaondo, Ana Mª Aransay, Rafael Prados-Rosales, Rebeca Martín, Juan Anguita, Leticia Abecia. The mitochondrial negative regulator MCJ modulates the interplay between microbiota and the host during ulcerative colitis. Scientific Reports. 2020; 10 (1):1-13.
Chicago/Turabian StyleMiguel Angel Pascual-Itoiz; Ainize Peña-Cearra; Itziar Martín-Ruiz; José Luis Lavín; Carolina Simó; Héctor Rodríguez; Estibaliz Atondo; Juana María Flores; Ana Carreras-González; Julen Tomás-Cortázar; Diego Barriales; Ainhoa Palacios; Virginia García-Cañas; Aize Pellón; Asier Fullaondo; Ana Mª Aransay; Rafael Prados-Rosales; Rebeca Martín; Juan Anguita; Leticia Abecia. 2020. "The mitochondrial negative regulator MCJ modulates the interplay between microbiota and the host during ulcerative colitis." Scientific Reports 10, no. 1: 1-13.
Glucocorticoids (GCs) are important hormones involved in the regulation of multiple physiologic functions. GCs are also widely used in anti-inflammatory/immunosuppressant drugs. GCs are synthesized by the adrenal cortex as part of the hypothalamus-pituitary-adrenal axis and also by intestinal epithelial cells, among other peripheral sites. GCs are one of the main therapy choices for the exacerbations of inflammatory bowel disease, but they are not useful to prolong remission, and development of tolerance with secondary treatment failure is frequent. Thus, GC actions at the intestinal epithelial level are of great importance, both physiologically and pharmacologically. We generated a tamoxifen-inducible nuclear receptor subfamily 3 group C member 1 (NR3C1)ΔIEC mouse model to study the effects of GCs on epithelial cells in vivo. Nr3c1 deletion in epithelial cells of the small intestine and colon was associated with limited colonic inflammation at 1 wk postdeletion, involving augmented epithelial proliferation and mucus production, plus local and systemic immune/inflammatory changes. This phenotype regressed substantially, but not completely, after 2 wk. The mechanism may involve augmented inflammatory signaling by epithelial cells or defective barrier function. We conclude that the epithelial GC receptor plays a significant role in colonic homeostasis in basal conditions, but its deficiency can be compensated in the short term. Future studies are required to assess the impact of Nr3c1 deletion in other conditions such as experimental colitis.—Aranda, C. J., Arredondo-Amador, M., Ocón, B., Lavín, J. L., Aransay, A. M., Martínez-Augustin, O., Sánchez de Medina, F. Intestinal epithelial deletion of the glucocorticoid receptor NR3C1 alters expression of inflammatory mediators and barrier function.
Carlos J. Aranda; María Arredondo-Amador; Borja Ocón; José Luis Lavín; Ana María Aransay; Olga Martínez-Augustin; Fermín Sánchez de Medina. Intestinal epithelial deletion of the glucocorticoid receptor NR3C1 alters expression of inflammatory mediators and barrier function. The FASEB Journal 2019, 33, 14067 -14082.
AMA StyleCarlos J. Aranda, María Arredondo-Amador, Borja Ocón, José Luis Lavín, Ana María Aransay, Olga Martínez-Augustin, Fermín Sánchez de Medina. Intestinal epithelial deletion of the glucocorticoid receptor NR3C1 alters expression of inflammatory mediators and barrier function. The FASEB Journal. 2019; 33 (12):14067-14082.
Chicago/Turabian StyleCarlos J. Aranda; María Arredondo-Amador; Borja Ocón; José Luis Lavín; Ana María Aransay; Olga Martínez-Augustin; Fermín Sánchez de Medina. 2019. "Intestinal epithelial deletion of the glucocorticoid receptor NR3C1 alters expression of inflammatory mediators and barrier function." The FASEB Journal 33, no. 12: 14067-14082.
Summary In recent years, the macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage CSF (GM-CSF) cytokines have been identified as opposing regulators of the inflammatory program. However, the two cytokines are simultaneously present in the inflammatory milieu, and it is not clear how cells integrate these signals. In order to understand the regulatory networks associated with the GM/M-CSF signaling axis, we analyzed DNA methylation in human monocytes. Our results indicate that GM-CSF induces activation of the inflammatory program and extensive DNA methylation changes, while M-CSF-polarized cells are in a less differentiated state. This inflammatory program is mediated via JAK2 associated with the GM-CSF receptor and the downstream extracellular signal-regulated (ERK) signaling. However, PI3K signaling is associated with a negative regulatory loop of the inflammatory program and M-CSF autocrine signaling in GM-CSF-polarized monocytes. Our findings describe the regulatory networks associated with the GM/M-CSF signaling axis and how they contribute to the establishment of the inflammatory program associated with monocyte activation.
Ramon M. Rodriguez; Beatriz Suarez-Alvarez; José Luis Lavín; Alex M. Ascensión; Monika Gonzalez; Juan J. Lozano; Aroa Baragaño Raneros; Paula D. Bulnes; Jose R. Vidal-Castiñeira; Covadonga Huidobro; Cristina Martin-Martin; Ana B. Sanz; Marta Ruiz-Ortega; Amaya Puig-Kröger; Angel L. Corbí; Marcos J. Araúzo-Bravo; Ana M. Aransay; Carlos Lopez-Larrea. Signal Integration and Transcriptional Regulation of the Inflammatory Response Mediated by the GM-/M-CSF Signaling Axis in Human Monocytes. Cell Reports 2019, 29, 860 -872.e5.
AMA StyleRamon M. Rodriguez, Beatriz Suarez-Alvarez, José Luis Lavín, Alex M. Ascensión, Monika Gonzalez, Juan J. Lozano, Aroa Baragaño Raneros, Paula D. Bulnes, Jose R. Vidal-Castiñeira, Covadonga Huidobro, Cristina Martin-Martin, Ana B. Sanz, Marta Ruiz-Ortega, Amaya Puig-Kröger, Angel L. Corbí, Marcos J. Araúzo-Bravo, Ana M. Aransay, Carlos Lopez-Larrea. Signal Integration and Transcriptional Regulation of the Inflammatory Response Mediated by the GM-/M-CSF Signaling Axis in Human Monocytes. Cell Reports. 2019; 29 (4):860-872.e5.
Chicago/Turabian StyleRamon M. Rodriguez; Beatriz Suarez-Alvarez; José Luis Lavín; Alex M. Ascensión; Monika Gonzalez; Juan J. Lozano; Aroa Baragaño Raneros; Paula D. Bulnes; Jose R. Vidal-Castiñeira; Covadonga Huidobro; Cristina Martin-Martin; Ana B. Sanz; Marta Ruiz-Ortega; Amaya Puig-Kröger; Angel L. Corbí; Marcos J. Araúzo-Bravo; Ana M. Aransay; Carlos Lopez-Larrea. 2019. "Signal Integration and Transcriptional Regulation of the Inflammatory Response Mediated by the GM-/M-CSF Signaling Axis in Human Monocytes." Cell Reports 29, no. 4: 860-872.e5.
Cold-pressed sunflower cake (CPSC), by-product of oil-manufacturing, has high crude fat and linoleic acid concentrations, being a promising supplement to modulate rumen fatty acid (FA) profile. This trial studied CPSC effects on ruminal fermentation, biohydrogenation and the bacterial community in dairy cows. Ten cows were used in a crossover design with two experimental diets and fed during two 63-day periods. The cows were group fed forage ad libitum and the concentrate individually. The concentrates, control and CPSC, were isoenergetic, isoproteic and isofat. The ruminal samples collected at the end of each experimental period were analyzed for short-chain fatty acid, FA and DNA sequencing. CPSC decreased butyrate molar proportion (4%, p = 0.005). CPSC decreased C16:0 (28%, p < 0.001) and increased C18:0 (14%, p < 0.001) and total monounsaturated FA, especially C18:1 trans-11 (13%, p = 0.023). The total purine derivative excretion tended to be greater (5%, p = 0.05) with CPSC, resulting in a 6% greater daily microbial N flow. CPSC did not affect the diversity indices but increased the relative abundances of Treponema and Coprococcus, and decreased Enterococcus, Ruminococcus and Succinivibrio. In conclusion, the changes in ruminal fermentation and the FA profile were not associated with changes in microbial diversity or abundance of dominant populations, however, they might be associated with less abundant genera.
Izaro Zubiria; Aser Garcia-Rodriguez; Raquel Atxaerandio; Roberto Ruiz; Hanen Benhissi; Nerea Mandaluniz; Jose Luis Lavín; Leticia Abecia; Idoia Goiri; Garcia- Rodriguez; Ruiz. Effect of Feeding Cold-Pressed Sunflower Cake on Ruminal Fermentation, Lipid Metabolism and Bacterial Community in Dairy Cows. Animals 2019, 9, 755 .
AMA StyleIzaro Zubiria, Aser Garcia-Rodriguez, Raquel Atxaerandio, Roberto Ruiz, Hanen Benhissi, Nerea Mandaluniz, Jose Luis Lavín, Leticia Abecia, Idoia Goiri, Garcia- Rodriguez, Ruiz. Effect of Feeding Cold-Pressed Sunflower Cake on Ruminal Fermentation, Lipid Metabolism and Bacterial Community in Dairy Cows. Animals. 2019; 9 (10):755.
Chicago/Turabian StyleIzaro Zubiria; Aser Garcia-Rodriguez; Raquel Atxaerandio; Roberto Ruiz; Hanen Benhissi; Nerea Mandaluniz; Jose Luis Lavín; Leticia Abecia; Idoia Goiri; Garcia- Rodriguez; Ruiz. 2019. "Effect of Feeding Cold-Pressed Sunflower Cake on Ruminal Fermentation, Lipid Metabolism and Bacterial Community in Dairy Cows." Animals 9, no. 10: 755.
Background Fibromyalgia is a complex, relatively unknown disease characterised by chronic, widespread musculoskeletal pain. The gut-brain axis connects the gut microbiome with the brain through the enteric nervous system (ENS); its disruption has been associated with psychiatric and gastrointestinal disorders. To gain an insight into the pathogenesis of fibromyalgia and identify diagnostic biomarkers, we combined different omics techniques to analyse microbiome and serum composition. Methods We collected faeces and blood samples to study the microbiome, the serum metabolome and circulating cytokines and miRNAs from a cohort of 105 fibromyalgia patients and 54 age- and environment-matched healthy individuals. We sequenced the V3 and V4 regions of the 16S rDNA gene from faeces samples. UPLC-MS metabolomics and custom multiplex cytokine and miRNA analysis (FirePlex™ technology) were used to examine sera samples. Finally, we combined the different data types to search for potential biomarkers. Results We found that the diversity of bacteria is reduced in fibromyalgia patients. The abundance of the Bifidobacterium and Eubacterium genera (bacteria participating in the metabolism of neurotransmitters in the host) in these patients was significantly reduced. The serum metabolome analysis revealed altered levels of glutamate and serine, suggesting changes in neurotransmitter metabolism. The combined serum metabolomics and gut microbiome datasets showed a certain degree of correlation, reflecting the effect of the microbiome on metabolic activity. We also examined the microbiome and serum metabolites, cytokines and miRNAs as potential sources of molecular biomarkers of fibromyalgia. Conclusions Our results show that the microbiome analysis provides more significant biomarkers than the other techniques employed in the work. Gut microbiome analysis combined with serum metabolomics can shed new light onto the pathogenesis of fibromyalgia. We provide a list of bacteria whose abundance changes in this disease and propose several molecules as potential biomarkers that can be used to evaluate the current diagnostic criteria.
Marc Clos-Garcia; Naiara Andrés-Marin; Gorka Fernández-Eulate; Leticia Abecia; José L. Lavín; Sebastiaan van Liempd; Diana Cabrera; Félix Royo; Alejandro Valero; Nerea Errazquin; María Cristina Gómez Vega; Leila Govillard; Michael R. Tackett; Genesis Tejada; Esperanza Gónzalez; Juan Anguita; Luis Bujanda; Ana María Callejo Orcasitas; Ana M. Aransay; Olga Maíz; Adolfo López de Munain; Juan Manuel Falcón-Pérez. Gut microbiome and serum metabolome analyses identify molecular biomarkers and altered glutamate metabolism in fibromyalgia. EBioMedicine 2019, 46, 499 -511.
AMA StyleMarc Clos-Garcia, Naiara Andrés-Marin, Gorka Fernández-Eulate, Leticia Abecia, José L. Lavín, Sebastiaan van Liempd, Diana Cabrera, Félix Royo, Alejandro Valero, Nerea Errazquin, María Cristina Gómez Vega, Leila Govillard, Michael R. Tackett, Genesis Tejada, Esperanza Gónzalez, Juan Anguita, Luis Bujanda, Ana María Callejo Orcasitas, Ana M. Aransay, Olga Maíz, Adolfo López de Munain, Juan Manuel Falcón-Pérez. Gut microbiome and serum metabolome analyses identify molecular biomarkers and altered glutamate metabolism in fibromyalgia. EBioMedicine. 2019; 46 ():499-511.
Chicago/Turabian StyleMarc Clos-Garcia; Naiara Andrés-Marin; Gorka Fernández-Eulate; Leticia Abecia; José L. Lavín; Sebastiaan van Liempd; Diana Cabrera; Félix Royo; Alejandro Valero; Nerea Errazquin; María Cristina Gómez Vega; Leila Govillard; Michael R. Tackett; Genesis Tejada; Esperanza Gónzalez; Juan Anguita; Luis Bujanda; Ana María Callejo Orcasitas; Ana M. Aransay; Olga Maíz; Adolfo López de Munain; Juan Manuel Falcón-Pérez. 2019. "Gut microbiome and serum metabolome analyses identify molecular biomarkers and altered glutamate metabolism in fibromyalgia." EBioMedicine 46, no. : 499-511.
Diet is one of the main factors affecting host’s health. The aim of this work was to study the interaction among nutrition, microbiota and host, using zebrafish adults as animal model. Thus, the effects of a high-saturated-fat diet, and its supplementation with a commercial fish-oil on fish lipid profile, intestinal microbiota and blood glucose were evaluated. The dietary saturated fat changed the fish lipid profile, microbial community composition, and its metabolism. Saturated fatty acids levels were higher in fish fed the high-saturated-fat diet, which correlated with an increased in Pseudomonas. Otherwise, the commercial fish-oil intake ameliorated the effect of the fat on the lipid profile, lowering saturated fatty acid levels while increasing polyunsaturated fatty acids. It also contributed to limit the growth of Pseudomonas on intestinal microbial community. Furthermore, blood glucose diminished in animals fed fish-oil supplemented diet. This suggests that fish-oil may mitigate the effect of the high-saturated-fat-diet.
Nerea Arias-Jayo; Leticia Abecia; José Luis Lavín; Itziar Tueros; Sara Arranz; Andoni Ramírez-García; Miguel Angel Pardo. Host-microbiome interactions in response to a high-saturated fat diet and fish-oil supplementation in zebrafish adult. Journal of Functional Foods 2019, 60, 103416 .
AMA StyleNerea Arias-Jayo, Leticia Abecia, José Luis Lavín, Itziar Tueros, Sara Arranz, Andoni Ramírez-García, Miguel Angel Pardo. Host-microbiome interactions in response to a high-saturated fat diet and fish-oil supplementation in zebrafish adult. Journal of Functional Foods. 2019; 60 ():103416.
Chicago/Turabian StyleNerea Arias-Jayo; Leticia Abecia; José Luis Lavín; Itziar Tueros; Sara Arranz; Andoni Ramírez-García; Miguel Angel Pardo. 2019. "Host-microbiome interactions in response to a high-saturated fat diet and fish-oil supplementation in zebrafish adult." Journal of Functional Foods 60, no. : 103416.
Steroid-refractoriness is a common and unpredictable phenomenon in ulcerative colitis (UC), but there are no conclusive studies on the molecular functions involved. We aimed to assess in depth the mechanism of action related to steroid failure by integrating transcriptomic data from UC patients, and updated molecular data on UC and glucocorticoids. miRNA and mRNA expression were evaluated by sequencing and microarrays, respectively, from rectal biopsies of patients with moderately-to-severe active UC, obtained before and on the 3rd day of steroid treatment. The differential results were integrated into the mathematical models generated by Systems Biology. This computational approach identified 18 proteins that stand out either by being associated to the mechanism of action or by providing a major capacity to classify the patients according to steroid response. Their biologicals functions have been linked with inflammation, glucocorticoid-induced transcription and angiogenesis. All the selected proteins but ANP32E (a chaperone which has been linked to the exchange of H2A.z histone and promotes glucocorticoid receptor-induced transcription) had previously been related to UC and/or glucocorticoid-induced biological actions. Western blot and immunofluorescence assays confirmed the implication of this chaperone in steroid failure in patients with active UC. A biology systems approach allowed to identify a comprehensive mechanism of action of steroid-refractoriness, highlighting the key role of steroid-induced transcription and the potential implication of ANP32E in this phenomenon.
V Lorén; A Garcia-Jaraquemada; J E Naves; X Carmona; M Mañosa; A M Aransay; José Luis Lavín; Ivelisse Sanchez; E Cabré; J Manyé; E Domènech. ANP32E, a Protein Involved in Steroid-Refractoriness in Ulcerative Colitis, Identified by a Systems Biology Approach. Journal of Crohn's and Colitis 2018, 13, 351 -361.
AMA StyleV Lorén, A Garcia-Jaraquemada, J E Naves, X Carmona, M Mañosa, A M Aransay, José Luis Lavín, Ivelisse Sanchez, E Cabré, J Manyé, E Domènech. ANP32E, a Protein Involved in Steroid-Refractoriness in Ulcerative Colitis, Identified by a Systems Biology Approach. Journal of Crohn's and Colitis. 2018; 13 (3):351-361.
Chicago/Turabian StyleV Lorén; A Garcia-Jaraquemada; J E Naves; X Carmona; M Mañosa; A M Aransay; José Luis Lavín; Ivelisse Sanchez; E Cabré; J Manyé; E Domènech. 2018. "ANP32E, a Protein Involved in Steroid-Refractoriness in Ulcerative Colitis, Identified by a Systems Biology Approach." Journal of Crohn's and Colitis 13, no. 3: 351-361.
Glycine N-methyltransferase (GNMT) is the most abundant methyltransferase in the liver and a master regulator of the transmethylation flux. GNMT downregulation leads to loss of liver function progressing to fibrosis, cirrhosis, and hepatocellular carcinoma. Moreover, GNMT deficiency aggravates cholestasis-induced fibrogenesis. To date, little is known about the mechanisms underlying downregulation of GNMT levels in hepatic fibrosis and cirrhosis. On this basis, microRNAs are epigenetic regulatory elements that play important roles in liver pathology. In this work, we aim to study the regulation of GNMT by microRNAs during liver fibrosis and cirrhosis. Luciferase assay on the 3'UTR-Gnmt was used to confirm in silico analysis showing that GNMT is potentially targeted by the microRNA miR-873-5p. Correlation between GNMT and miR-873-5p in human cholestasis and cirrhosis together with miR-873-5p inhibition in vivo in different mouse models of liver cholestasis and fibrosis [bile duct ligation and Mdr2 (Abcb4)-/- mouse] were then assessed. The analysis of liver tissue from cirrhotic and cholestatic patients, as well as from the animal models, showed that miR-873-5p inversely correlated with the expression of GNMT. Importantly, high circulating miR-873-5p was also detected in cholestastic and cirrhotic patients. Preclinical studies with anti-miR-873-5p treatment in bile duct ligation and Mdr2-/- mice recovered GNMT levels in association with ameliorated inflammation and fibrosis mainly by counteracting hepatocyte apoptosis and cholangiocyte proliferation. In conclusion, miR-873-5p emerges as a novel marker for liver fibrosis, cholestasis, and cirrhosis and therapeutic approaches based on anti-miR-873-5p may be effective treatments for liver fibrosis and cholestatic liver disease.
David Fernández-Ramos; Pablo Fernández-Tussy; Fernando Lopitz-Otsoa; Virginia Gutiérrez-De-Juan; Nicolás Navasa; Lucía Barbier-Torres; Imanol Zubiete-Franco; Jorge Simón; Agustín F. Fernández; Ander Arbelaiz; Ana M. Aransay; José Luis Lavín; Naiara Beraza; María J. Perugorria; Jesus M. Banales; Erica Villa; Mario Fraga; Juan Anguita; Matias Avila; Carmen Berasain; Paula Iruzibieta; Javier Crespo; Shelly C. Lu; Marta Varela-Rey; José M. Mato; Teresa C. Delgado; María L. Martínez-Chantar. MiR-873-5p acts as an epigenetic regulator in early stages of liver fibrosis and cirrhosis. Cell Death & Disease 2018, 9, 958 .
AMA StyleDavid Fernández-Ramos, Pablo Fernández-Tussy, Fernando Lopitz-Otsoa, Virginia Gutiérrez-De-Juan, Nicolás Navasa, Lucía Barbier-Torres, Imanol Zubiete-Franco, Jorge Simón, Agustín F. Fernández, Ander Arbelaiz, Ana M. Aransay, José Luis Lavín, Naiara Beraza, María J. Perugorria, Jesus M. Banales, Erica Villa, Mario Fraga, Juan Anguita, Matias Avila, Carmen Berasain, Paula Iruzibieta, Javier Crespo, Shelly C. Lu, Marta Varela-Rey, José M. Mato, Teresa C. Delgado, María L. Martínez-Chantar. MiR-873-5p acts as an epigenetic regulator in early stages of liver fibrosis and cirrhosis. Cell Death & Disease. 2018; 9 (10):958.
Chicago/Turabian StyleDavid Fernández-Ramos; Pablo Fernández-Tussy; Fernando Lopitz-Otsoa; Virginia Gutiérrez-De-Juan; Nicolás Navasa; Lucía Barbier-Torres; Imanol Zubiete-Franco; Jorge Simón; Agustín F. Fernández; Ander Arbelaiz; Ana M. Aransay; José Luis Lavín; Naiara Beraza; María J. Perugorria; Jesus M. Banales; Erica Villa; Mario Fraga; Juan Anguita; Matias Avila; Carmen Berasain; Paula Iruzibieta; Javier Crespo; Shelly C. Lu; Marta Varela-Rey; José M. Mato; Teresa C. Delgado; María L. Martínez-Chantar. 2018. "MiR-873-5p acts as an epigenetic regulator in early stages of liver fibrosis and cirrhosis." Cell Death & Disease 9, no. 10: 958.
SummaryGenes sharing functions, expression patterns or quantitative traits are not randomly distributed along eukaryotic genomes. In order to study the distribution of genes that share a given feature, we present Cluster Locator, an online analysis and visualization tool. Cluster Locator determines the number, size and position of all the clusters formed by the protein-coding genes on a list according to a given maximum gap, the percentage of gene clustering of the list and its statistical significance. The output includes a visual representation of the distribution of genes and gene clusters along the reference genome.Availability and implementationCluster Locator is freely available at http://clusterlocator.bnd.edu.uy/.Supplementary informationSupplementary data are available at Bioinformatics online.
Flavio Pazos Obregón; Pablo Soto; José Luis Lavín; Ana Rosa Cortazar; Rosa Barrio; Ana María Aransay; Rafael Cantera. Cluster Locator, online analysis and visualization of gene clustering. Bioinformatics 2018, 34, 3377 -3379.
AMA StyleFlavio Pazos Obregón, Pablo Soto, José Luis Lavín, Ana Rosa Cortazar, Rosa Barrio, Ana María Aransay, Rafael Cantera. Cluster Locator, online analysis and visualization of gene clustering. Bioinformatics. 2018; 34 (19):3377-3379.
Chicago/Turabian StyleFlavio Pazos Obregón; Pablo Soto; José Luis Lavín; Ana Rosa Cortazar; Rosa Barrio; Ana María Aransay; Rafael Cantera. 2018. "Cluster Locator, online analysis and visualization of gene clustering." Bioinformatics 34, no. 19: 3377-3379.