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5. Developmental Stage, Muscle and Genetic Type Modify Muscle Transcriptome in Pigs: Effects on Gene Expression and Regulatory Factors Involved in Growth and Metabolism

Author

Ayuso, Miriam, Fernández, Almudena, Núñez, Yolanda, Benítez, Rita, Isabel, Beatriz, Fernández, Ana I, Rey, Ana I, González-Bulnes, Antonio, Medrano, Juan F, Cánovas, Ángela, López-Bote, Clemente J, and Óvilo, Cristina

Subjects
Agricultural, Veterinary and Food Sciences, Biological Sciences, Genetics, Zoology, Animal Production, Pediatric, Biotechnology, Perinatal Period - Conditions Originating in Perinatal Period, 2.1 Biological and endogenous factors, Aetiology, Animals, Female, Gene Expression, Muscle, Skeletal, Swine, Transcriptome, General Science & Technology
Abstract

Iberian pig production includes purebred (IB) and Duroc-crossbred (IBxDU) pigs, which show important differences in growth, fattening and tissue composition. This experiment was conducted to investigate the effects of genetic type and muscle (Longissimus dorsi (LD) vs Biceps femoris (BF)) on gene expression and transcriptional regulation at two developmental stages. Nine IB and 10 IBxDU piglets were slaughtered at birth, and seven IB and 10 IBxDU at four months of age (growing period). Carcass traits and LD intramuscular fat (IMF) content were measured. Muscle transcriptome was analyzed on LD samples with RNA-Seq technology. Carcasses were smaller in IB than in IBxDU neonates (p < 0.001), while growing IB pigs showed greater IMF content (p < 0.05). Gene expression was affected (p < 0.01 and Fold change > 1.5) by the developmental stage (5,812 genes), muscle type (135 genes), and genetic type (261 genes at birth and 113 at growth). Newborns transcriptome reflected a highly proliferative developmental stage, while older pigs showed upregulation of catabolic and muscle functioning processes. Regarding the genetic type effect, IBxDU newborns showed enrichment of gene pathways involved in muscle growth, in agreement with the higher prenatal growth observed in these pigs. However, IB growing pigs showed enrichment of pathways involved in protein deposition and cellular growth, supporting the compensatory gain experienced by IB pigs during this period. Moreover, newborn and growing IB pigs showed more active glucose and lipid metabolism than IBxDU pigs. Moreover, LD muscle seems to have more active muscular and cell growth, while BF points towards lipid metabolism and fat deposition. Several regulators controlling transcriptome changes in both genotypes were identified across muscles and ages (SIM1, PVALB, MEFs, TCF7L2 or FOXO1), being strong candidate genes to drive expression and thus, phenotypic differences between IB and IBxDU pigs. Many of the identified regulators were known to be involved in muscle and adipose tissues development, but others not previously associated with pig muscle growth were also identified, as PVALB, KLF1 or IRF2. The present study discloses potential molecular mechanisms underlying phenotypic differences observed between IB and IBxDU pigs and highlights candidate genes implicated in these molecular mechanisms.

Published
2016

7. Increased Chamber Resting Tone Is a Key Determinant of Left Ventricular Diastolic Dysfunction

Author

Tamargo, María, primary, Martínez-Legazpi, Pablo, additional, Espinosa, M. Ángeles, additional, Lyon, Aurore, additional, Méndez, Irene, additional, Gutiérrez-Ibañes, Enrique, additional, Fernández, Ana I., additional, Prieto-Arévalo, Raquel, additional, González-Mansilla, Ana, additional, Arts, Theo, additional, Delhaas, Tammo, additional, Mombiela, Teresa, additional, Sanz-Ruiz, Ricardo, additional, Elízaga, Jaime, additional, Yotti, Raquel, additional, Tschöpe, Carsten, additional, Fernández-Avilés, Francisco, additional, Lumens, Joost, additional, and Bermejo, Javier, additional

Published
2023
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9. Microbiome profile and calprotectin levels as markers of risk of recurrent Clostridioides difficile infection

Author

Vázquez-Cuesta, Silvia, primary, Lozano García, Nuria, additional, Fernández, Ana I., additional, Olmedo, María, additional, Kestler, Martha, additional, Alcalá, Luis, additional, Marín, Mercedes, additional, Bermejo, Javier, additional, Díaz, Francisco Fernández-Avilés, additional, Muñoz, Patricia, additional, Bouza, Emilio, additional, and Reigadas, Elena, additional

Published
2023
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20. Characterization of the gut microbiome of patients with Clostridioides difficile infection, patients with non–C. difficile diarrhea, and C. difficile–colonized patients

Author

Vázquez-Cuesta, Silvia, primary, Villar, Laura, additional, García, Nuria Lozano, additional, Fernández, Ana I., additional, Olmedo, María, additional, Alcalá, Luis, additional, Marín, Mercedes, additional, Muñoz, Patricia, additional, Bouza, Emilio, additional, and Reigadas, Elena, additional

Published
2023
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27. Cardiovascular Diseases in the Digital Health Era: A Translational Approach from the Lab to the Clinic

Author

Sánchez de la Nava, Ana María, primary, Gómez-Cid, Lidia, additional, Ríos-Muñoz, Gonzalo Ricardo, additional, Fernández-Santos, María Eugenia, additional, Fernández, Ana I., additional, Arenal, Ángel, additional, Sanz-Ruiz, Ricardo, additional, Grigorian-Shamagian, Lilian, additional, Atienza, Felipe, additional, and Fernández-Avilés, Francisco, additional

Published
2022
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29. Flexible Tools for Gene Expression and Silencing in Tomato

Author

Fernandez, Ana I., Viron, Nicolas, Alhagdow, Moftah, Karimi, Mansour, Jones, Matthew, Amsellem, Ziva, Sicard, Adrien, Czerednik, Anna, Angenent, Gerco, Grierson, Donald, May, Sean, Seymour, Graham, Eshed, Yuval, Lemaire-Chamley, Martine, Rothan, Christophe, and Hilson, Pierre

Published
2009
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30. Diseño y fabricación de una órtesis activa para descarga de peso

Author

Gallego-Miguel, A., García Haro, Juan Miguel, Bautista, S., Simon Rodriguez, M.A., Velasco-Fernández, Ana-I, Gallego-Miguel, A., García Haro, Juan Miguel, Bautista, S., Simon Rodriguez, M.A., and Velasco-Fernández, Ana-I

Abstract

[Resumen] Cada día, un mayor número de personas sufren algún tipo de accidente, que termina derivando en una reducción de la movilidad de alguna extremidad o parte del cuerpo humano. Como consecuencia, la calidad de vida de estas personas se ve considerablemente reducida. Particularmente, una patología asociada a esta situación es la osteocondritis disecante del astrágalo, la cual produce fuertes dolores cuando se apoya el peso del cuerpo sobre el tobillo. Para intentar prevenir o aliviar dicho dolor, este artículo se centra en el diseño, prototipado y comprobación de una órtesis de descarga. Dicho dispositivo no tiene como objetivo asistir en el movimiento de flexo-extensión del tobillo, como la mayoría de las soluciones existentes, sino en descargar de manera axial y redistribuir el peso de forma externa al tobillo. Con este planteamiento, a través de una serie de pruebas y cuestionarios, se ha ido verificando la evolución de los pacientes antes, durante y después de usar la órtesis., [Abstract] Every day, a greater number of people suffer some type of accident, which ends up resulting in a reduction of the mobility of some limb or part of the human body. As a consequence, the quality of life of these people is considerably reduced. Particularly, a pathology associated with this situation is osteochondritis dissecans of the astragalus, which causes severe pain when the weight of the body is supported on the ankle. In an attempt to prevent or relieve such pain, this article focuses on the design, prototyping and testing of an unloading orthosis. This device does not aim to assist in the dorsiflexion ans plantarflexion movement of the ankle, as most existing solutions do. It pretends to offload axially and redistribute weight externally to the ankle. With this approach, through a series of tests and questionnaires, the evolution of the patients before, during and after using the orthosis has been verified.

Published
2022

37. Persistent Pulmonary Hypertension in Corrected Valvular Heart Disease: Hemodynamic Insights and Long-Term Survival

Author

Bermejo, Javier, González-Mansilla, Ana, Mombiela, Teresa, Fernández, Ana I., Martínez-Legazpi, Pablo, Yotti, Raquel, García-Orta, Rocío, Sánchez-Fernández, Pedro L., Castaño, Mario, Segovia-Cubero, Javier, Escribano-Subias, Pilar, San Román, J.Alberto, Borràs Pino, Xavier, Alonso-Gómez, Ángel María, Botas, Javier, Crespo-Leiro, Maria Generosa, Velasco, Sonia, Bayés-Genís, Antoni, López, Amador, Muñoz-Aguilera, Roberto, Jiménez-Navarro, Manuel, González-Juanatey, José R., Evangelista, Arturo, Elízaga, Jaime, Martín-Moreiras, Javier, González-Santos, José M., Moreno-Escobar, Eduardo, Fernández Avilés, F., García-Robles, José A., Pérez-David, Esther, Pérez Del Villar, Candelas, Sanz, Ricardo, Gutierrez-Ibanes, Enrique, Vázquez, María E., Mur, Ana, Benito, Yolanda, Barrio, Alicia, Vázquez, Alexandra, Uribe, Inés, González, Mercedes, Arribas, Antonio, Clemente Lorenzo, M. Milagros, Nieto, Alejandro Diego, Pérez De Prado, Armando, Alonso, David, Gómez-Bueno, Manuel, Sayago Silva, Inés, Cavero, Miguel Ángel, Domínguez, Laura, Tello De Meneses, Rocío, Ruíz Cano, María José, Jiménez López-Guarch, Carmen, Mota, Pedro, Amorós Galitó, Carmen, Belló Mora, M. Concepción, Mesa Rubio, Dolores, Campuzano, Raquel, Marzoa, Raquel, Cuenca, José, Muñoz, Roberto, Suberviola, Verónica, Beltrán Herrera, Cristina, Mora, Laura, Sarrión, M. Mar, Vaqueriza, David, Ferrer, Elena, Cid-Álvarez, Belén, Martínez Monzonís, Amparo, Arizón De Prado, José M., Santisteban, Marta, García-Dorado, David, De Teresa, Eduardo, Carrasco-Chinchilla, Fernando, Alonso, Joaquín, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), European Regional Development Fund (ERDF/FEDER), Centro de Investigación Biomedica en Red - CIBER, Institut Català de la Salut, [Bermejo J, González-Mansilla A, Mombiela T, Fernández AI, Martínez-Legazpi P] Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Facultad de Medicina, Universidad Complutense de Madrid, and CIBERCV Madrid Spain. [Yotti R] Instituto de Salud Carlos III Madrid Spain. [Evangelista A] Vall d'Hebron Hospital Universitari, Barcelona, Spain. CIBERCV Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Male, Heart Valve Diseases, Hemodynamics, Long Term Adverse Effects, heart failure, 030204 cardiovascular system & hematology, Valvular heart diseas, 0302 clinical medicine, Postoperative Complications, Risk Factors, Hipertensió pulmonar - Factors de risc, pulmonary hypertension, 030212 general & internal medicine, Original Research, Heart Valve Prosthesis Implantation, valvular heart disease, Organ Size, Middle Aged, Heart Valves, Cardiology, Female, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, enfermedades respiratorias::enfermedades pulmonares::hipertensión pulmonar [ENFERMEDADES], Hypertension, Pulmonary, Heart failure, enfermedades cardiovasculares::enfermedades cardíacas::enfermedades de las válvulas cardíacas [ENFERMEDADES], técnicas de investigación::métodos epidemiológicos::estadística como asunto::probabilidad::riesgo::factores de riesgo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Sildenafil Citrate, Pulmonary hypertension, 03 medical and health sciences, Respiratory Tract Diseases::Lung Diseases::Hypertension, Pulmonary [DISEASES], Double-Blind Method, Internal medicine, Long term survival, medicine, Diabetes Mellitus, Humans, Pulmonary Wedge Pressure, business.industry, Persistent pulmonary hypertension, Cor - Vàlvules - Malalties, Phosphodiesterase 5 Inhibitors, medicine.disease, Valvular heart disease, Valvular Heart Disease, Cardiovascular Diseases::Heart Diseases::Heart Valve Diseases [DISEASES], Vascular Resistance, Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], business
Abstract

Background The determinants and consequences of pulmonary hypertension after successfully corrected valvular heart disease remain poorly understood. We aim to clarify the hemodynamic bases and risk factors for mortality in patients with this condition. Methods and Results We analyzed long‐term follow‐up data of 222 patients with pulmonary hypertension and valvular heart disease successfully corrected at least 1 year before enrollment who had undergone comprehensive hemodynamic and imaging characterization as per the SIOVAC (Sildenafil for Improving Outcomes After Valvular Correction) clinical trial. Median (interquartile range) mean pulmonary pressure was 37 mm Hg (32–44 mm Hg) and pulmonary artery wedge pressure was 23 mm Hg (18–26 mm Hg). Most patients were classified either as having combined precapillary and postcapillary or isolated postcapillary pulmonary hypertension. After a median follow‐up of 4.5 years, 91 deaths accounted for 4.21 higher‐than‐expected mortality in the age‐matched population. Risk factors for mortality were male sex, older age, diabetes mellitus, World Health Organization functional class III and higher pulmonary vascular resistance—either measured by catheterization or approximated from ultrasound data. Higher pulmonary vascular resistance was related to diabetes mellitus and smaller residual aortic and mitral valve areas. In turn, the latter correlated with prosthetic nominal size. Six‐month changes in the composite clinical score and in the 6‐minute walk test distance were related to survival. Conclusions Persistent valvular heart disease–pulmonary hypertension is an ominous disease that is almost universally associated with elevated pulmonary artery wedge pressure. Pulmonary vascular resistance is a major determinant of mortality in this condition and is related to diabetes mellitus and the residual effective area of the corrected valve. These findings have important implications for individualizing valve correction procedures. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00862043.

Published
2021

43. The Essential Need for a Validated Potency Assay for Cell-Based Therapies in Cardiac Regenerative and Reparative Medicine. A Practical Approach to Test Development

Author

Gómez Cid, Lidia, Grigorian Shamagian, Lilian, Sanz Ruiz, Ricardo, Nava, Ana S. de la, Fernández, Ana I., Fernández Santos, María Eugenia, Fernández-Avilés Díaz, Francisco, Gómez Cid, Lidia, Grigorian Shamagian, Lilian, Sanz Ruiz, Ricardo, Nava, Ana S. de la, Fernández, Ana I., Fernández Santos, María Eugenia, and Fernández-Avilés Díaz, Francisco

Abstract

CRUE-CSIC (Acuerdos Transformativos 2021), Biological treatments are one of the medical breakthroughs in the twenty-first century. The initial enthusiasm pushed the field towards indiscriminatory use of cell therapy regardless of the pathophysiological particularities of underlying conditions. In the reparative and regenerative cardiovascular field, the results of the over two decades of research in cell-based therapies, although promising still could not be translated into clinical scenario. Now, when we identified possible deficiencies and try to rebuild its foundations rigorously on scientific evidence, development of potency assays for the potential therapeutic product is one of the steps which will bring our goal of clinical translation closer. Although, highly challenging, the potency tests for cell products are considered as a priority by the regulatory agencies. In this paper we describe the main characteristics and challenges for a cell therapy potency test focusing on the cardiovascular field. Moreover, we discuss different steps and types of assays that should be taken into consideration for an eventual potency test development by tying together two fundamental concepts: target disease and expected mechanism of action., Instituto de Salud Carlos III (ISCIII)/MICINN, Depto. de Medicina, Fac. de Medicina, TRUE, pub

Published
2021

48. The impact of Mediterranean diet on coronary plaque vulnerability, microvascular function, inflammation and microbiome after an acute coronary syndrome: study protocol for the MEDIMACS randomized, controlled, mechanistic clinical trial.

Author

Fernández, Ana I., Bermejo, Javier, Yotti, Raquel, Martínez-Gonzalez, Miguel Ángel, Mira, Alex, Gophna, Uri, Karlsson, Roger, Al-Daccak, Reem, Martín-Demiguel, Irene, Gutiérrez-Ibanes, Enrique, Charron, Dominique, Fernández-Avilés, Francisco, on behalf of the MEDIMACS research team, Gutierrez-Ibanes, Enrique, Gabaldón-Badiola, Álvaro, Sanz, Ricardo, Martínez-Legazpi, Pablo, Elízaga, Jaime, Jurado, Elena, and Razquin, Cristina

Subjects
*MEDITERRANEAN diet, *ACUTE coronary syndrome, *RESEARCH protocols, *CORONARY artery disease, *OPTICAL coherence tomography
Abstract

Background: Primary prevention trials have demonstrated that the traditional Mediterranean diet is associated with a reduction in cardiovascular mortality and morbidity. However, this benefit has not been proven for secondary prevention after an acute coronary syndrome (ACS). We hypothesized that a high-intensity Mediterranean diet intervention after an ACS decreases the vulnerability of atherosclerotic plaques by complex interactions between anti-inflammatory effects, microbiota changes and modulation of gene expression.Methods: The MEDIMACS project is an academically funded, prospective, randomized, controlled and mechanistic clinical trial designed to address the effects of an active randomized intervention with the Mediterranean diet on atherosclerotic plaque vulnerability, coronary endothelial dysfunction and other mechanistic endpoints. One hundred patients with ACS are randomized 1:1 to a monitored high-intensity Mediterranean diet intervention or to a standard-of-care arm. Adherence to diet is assessed in both arms using food frequency questionnaires and biomarkers of compliance. The primary endpoint is the change (from baseline to 12 months) in the thickness of the fibrous cap of a non-significant atherosclerotic plaque in a non-culprit vessel, as assessed by repeated optical coherence tomography intracoronary imaging. Indices of coronary vascular physiology and changes in gastrointestinal microbiota, immunological status and protein and metabolite profiles will be evaluated as secondary endpoints.Discussion: The results of this trial will address the key effects of dietary habits on atherosclerotic risk and will provide initial data on the complex interplay of immunological, microbiome-, proteome- and metabolome-related mechanisms by which non-pharmacological factors may impact the progression of coronary atherosclerosis after an ACS.Trial Registration: ClinicalTrials.gov NCT03842319 . Registered on 13 May 2019. [ABSTRACT FROM AUTHOR]

Published
2021
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50. Dificultades de los investigadores españoles para publicar en revistas internacionales: métricas, editores y multilingüismo

Author

López Navarro, Irene [0000-0001-9013-6128], Rey-Rocha, Jesús [0000-0002-0122-1601], Moreno Fernández, Ana I. [0000-0003-1369-0883], López Navarro, Irene, Moreno Fernández, Ana I., Rey-Rocha, Jesús, López Navarro, Irene [0000-0001-9013-6128], Rey-Rocha, Jesús [0000-0002-0122-1601], Moreno Fernández, Ana I. [0000-0003-1369-0883], López Navarro, Irene, Moreno Fernández, Ana I., and Rey-Rocha, Jesús

Abstract

[ES] Throughout history, there have been several languages, such as German, French or English, which have gained the status of lingua franca of international scientific communication. However, contemporary science has witnessed a significant increase in the use of English for scholarly communication. As a result, nowadays, scientific records written in languages other than English are increasingly scarce, hence, perpetuating English as a lingua franca in this context. This situation has brought about many difficulties and inequalities that non-Anglophone researchers need to face when it comes to developing their professional activity. It has also given rise to a change in researchers´ patterns of publication associated with their attitudes towards the languages they can choose to communicate their results. In this paper, we offer a state-of-the-art review and analyze the data available from the main studies that have been carried out in Spain and in other non-Anglophone contexts. Finally, pedagogical, economic and political implications are discussed.

Published
2017

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