159 research outputs found

    Novel insights into maintaining genomic integrity: Wee1 regulating Mus81/Eme1

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    Maintenance of genomic integrity is essential for cell survival. Specifically, during DNA replication cells use a complex network of mechanisms that prevents genomic instability. Recently, we and others identified Wee1, a serine/threonine and tyrosine kinase, as a new modulator of the genomic stability during S phase. Loss of its activity causes a general DNA damage response activation and a decrease in replication fork speed. These effects are counteracted by the downregulation of the endonuclease complex Mus81-Eme1, showing a new link between this endonuclease and Wee1 during DNA replication. Here we discuss the function of Wee1 in genomic stability and its relationship with the Mus81-Eme1 complex

    Clinical and economic value of sofosbuvir-based regimens in the treatment of chronic hepatitis C in Spain

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    Chronic hepatitis C; Economic valueHepatitis C crónica; Valor económicoHepatitis C crònica; Valor econòmicBackground The treatment of chronic hepatitis C virus (HCV) with direct-acting antivirals has undergone a spectacular revolution and added significant value to healthcare systems and patients. The aim of the study was to evaluate the efficiency and value of Sofosbuvir (SOF)-based regimens for a target population of 85,959 chronic HCV patients treated in Spain during 2015–2019, compared to previous therapeutic strategies (peginterferon/ and ribavirin in double/triple therapy with telaprevir or boceprevir). Methods A previously developed lifetime Markov model was adapted to simulate the disease HCV evolution. In SOF-based regimens, all patients (100%) were treated regardless with sustained virological response (SVR) of 93–98%, obtained from real-world data. In previous therapeutic, only ≥F2 patients were treated according to clinical practice (38%) with an average SVR of 61% taken from published literature. The value was measured as clinical and economic impact in terms of avoided HCV-related mortality and liver complications; total costs and quality-adjusted life years (QALYs) applying an annual 3% discount rate. Results Compared to previous therapeutic, during lifetime, SOF-based regimens reduced decompensated cirrhosis by 89%, hepatocellular carcinoma by 77% and liver transplant by 84%, decreasing the cost associated to liver complications management in €770 million. SOF-based regimens also decreased liver-related mortality by 82%. Besides, SOF-based regimens gained 310,765/QALYs, saving €274 million (considering drugs, monitoring, and HCV management). Conclusion For Spain, SOF-based regimens offer value for HCV patients in terms of lowering HCV-related liver disease burden and generating significant cost savings for the health system, contributing to the WHO goal.The study was funded by Gilead Spain Sciences. In addition, “The funder did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section”

    Enzyme-Catalyzed Polymerization of Kraft Lignin from Eucalyptus globulus: Comparison of Bacterial and Fungal Laccases Efficacy

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    Kraft lignin, a side-stream from the pulp and paper industry, can be modified by laccases for the synthesis of high added-value products. This work aims to study different laccase sources, including a bacterial laccase from Streptomyces ipomoeae (SiLA) and a fungal laccase from Myceliophthora thermophila (MtL), for kraft lignin polymerization. To study the influence of some variables in these processes, a central composite design (CCD) with two continuous variables (enzyme concentration and reaction time) and three levels for each variable was used. The prediction of the behavior of the output variables (phenolic content and molecular weight of lignins) were modelled by means of response surface methodology (RSM). Moreover, characterization of lignins was performed by Fourier-transform infrared (FTIR) spectroscopy and different nuclear magnetic resonance (NMR) spectroscopy techniques. In addition, antioxidant activity was also analyzed. Results showed that lignin polymerization (referring to polymerization as lower phenolic content and higher molecular weight) occurred by the action of both laccases. The enzyme concentration was the most influential variable in the lignin polymerization reaction within the range studied for SiLA laccase, while the most influential variable for MtL laccase was the reaction time. FTIR and NMR characterization analysis corroborated lignin polymerization results obtained from the RSM.This research was funded by Comunidad de Madrid via Project SUSTEC-CM S2018/EMT-4348; MICINN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe” via Project RTI2018-096080-B-C22; and MICINN via Project TED2021-132122B-C21

    Detection of NOTCH1 mutations in paraffin samples in patients with potentially malignant lesions

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    On certain occasions, oral cancer is preceded by potentially malignant lesions. The degree of dysplasia in Guinea pigs attempts to determine the risk of developing a malignant lesion. The search for genetic mutations, biomarkers, as a more truthful and r

    Angiotensin II type 2 receptor as a novel activator of brown adipose tissue in obesity

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    The angiotensin II type 2 receptor (AT2R) exerts vasorelaxant, anti-inflammatory, and antioxidant properties. In obesity, its activation counterbalances the adverse cardiovascular effects of angiotensin II mediated by the AT1R. Preliminary results indicate that it also promotes brown adipocyte differentiation in vitro. Our hypothesis is that AT2R activation could increase BAT mass and activity in obesity. Five-week-old male C57BL/6J mice were fed a standard or a high-fat (HF) diet for 6 weeks. Half of the animals were treated with compound 21 (C21), a selective AT2R agonist, (1 mg/kg/day) in the drinking water. Electron transport chain (ETC), oxidative phosphorylation, and UCP1 proteins were measured in the interscapular BAT (iBAT) and thoracic perivascular adipose tissue (tPVAT) as well as inflammatory and oxidative parameters. Differentiation and oxygen consumption rate (OCR) in the presence of C21 was tested in brown preadipocytes. In vitro, C21-differentiated brown adipocytes showed an AT2R-dependent increase of differentiation markers (Ucp1, Cidea, Pparg) and increased basal and H+ leak-linked OCR. In vivo, HF-C21 mice showed increased iBAT mass compared to HF animals. Both their iBAT and tPVAT showed higher protein levels of the ETC protein complexes and UCP1, together with a reduction of inflammatory and oxidative markers. The activation of the AT2R increases BAT mass, mitochondrial activity, and reduces markers of tissue inflammation and oxidative stress in obesity. Therefore, insulin reduction and better vascular responses are achieved. Thus, the activation of the protective arm of the renin–angiotensin system arises as a promising tool in the treatment of obesity15 página

    Internacionalización y convergencia de las variaciones en los métodos docentes en Prótesis Estomatológica, iniciados y proyectados a raíz de la pandemia por Covid-19, en las facultades europeas de Odontología durante el último curso de Grado

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    Investigar los cambios (propiciados por la pandemia de Covid-19) en la docencia de prótesis en 5º de Odontología en Europa durante el curso 2020-21. Para ello hemos diseñado y distribuido un cuestionario acerca de la dedicación presencial, telemática y asistencial con pacientes. Estamos iniciando una red de trabajo europea para compartir la retroalimentación de este proyecto y las experiencias de los compañeros que coordinan esta disciplina en otras facultades europeas, para fomentar el proceso de convergencia al EEES en un momento tan crucial como el que estamos viviendo

    Mapas Conceptuales y Aprendizaje Cooperativo : una visión desde la enseñanza universitaria

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    El libro que se presenta bajo el título “Mapas Conceptuales y Aprendizaje Cooperativo. Una visión desde la enseñanza universitaria, constituye uno de los resultados del trabajo de un grupo de profesores y especialistas suscrito en el Proyecto de Innovación “ Los Mapas Conceptuales como metodología docente activa dentro del Nuevo Espacio de Educación Superior Europeo”, Finestra Oberta.UV-SFPIE_2014_221354, bajo la dirección de la profesora María Elena Cobas Cobiella, del Departamento de Derecho Civil, de la Facultad de Derecho, Universidad de Valencia. Este libro tiene además la peculiaridad que participan estudiantes de Grado, del Máster Universitario en Mediación, Arbitraje y Gestión de Conflictos en Derecho Privado (curso 2014- 2015), así como de la Maestría en Estudios Jurídicos con orientación en Derecho Constitucional y Derecho de la persona y Doctorado de la Universidad Juárez Autónoma de Tabasco y del Doctorado en Estudios Jurídicos, con las experiencias de sus respectivos trabajos en clase. El libro recoge las experiencias del profesorado y personal colaborador en la innovación en esta temática, y su aplicación práctica a diversas asignaturas y cursos de Derecho, dobles grados, Derecho y ADE, Derecho y criminología, Derecho y Ciencias Políticas, entre otras disciplinas. Los profesores universitarios y especialistas del derecho nos cuentan sus impresiones y nos recrean con ejemplos su forma de trabajar y ver la docencia desde la práctica. El Libro consta de varias partes, siguiendo una estructura metodológica ordenada. La Parte General recoge los trabajos de los profesores y especialistas en la materia, y sus experiencias en el desarrollo tanto del aprendizaje cooperativo, como del empleo de la metodología de innovación educativa de los mapas conceptuales, en la Parte Especial se exponen los trabajos de los estudiantes de Grado, como de los estudiantes de Master y Doctorado, con la peculiaridad de que este libro tiene un apartado dedicado al área internacional, porque los estudiantes de la Maestría en Estudios Jurídicos con orientación en Derecho Constitucional y Derecho de la persona y Doctorado de la Universidad Juárez Autónoma de Tabasco, México han participado bajo la dirección de las profesoras e investigadoras del Programa de Estudios de Doctorado de la citada Universidad. Igualmente en el Libro aparecen las aportaciones de los estudiantes de la Universidad de Valencia, de la primera Edición del Máster Universitario en Mediación, Arbitraje y Gestión de Conflictos en Derecho Privado (curso 2014- 2015), en el Módulo impartido por la Dra Cobas, en la materia de Mediación y Arbitraje en Derecho de Sucesiones y Empresa familiar. El prólogo de la cita obra fue realizado por la Dra Pérez Fuentes, profesora investigadora de la Alta Casa de Estudios de la Universidad Juárez Autónoma de Tabasco, México.The book presented under the title "Concept maps and cooperative learning". A view from university education, represents one of the results of the work of a group of professors and specialists involved in the Innovation Project "Concept Maps as an active teaching methodology within the new European Higher Education Area" Finestra Oberta, UV- SFPIE_2014_221354, under the direction of Professor Maria Elena Cobas Cobiella, Department of Civil Law, Faculty of Law, University of Valencia. This book also has the peculiarity that are involved undergraduate students, students from the Master in Mediation, students from the course "Arbitration and Conflict Management in Private Law" (course 2014-2015), from the Master of Legal Studies in relation with the constitutional law and the law person and finally students from the Doctorate program of the Universidad Juárez Autónoma de Tabasco and from the Doctorate in Legal Studies, with the experiences of their works in class.Figuran también como autores y colaboradores del libro, los siguientes estudiantes:Alba Albert Garrido, Jorge González Molina, María Belén Fernández Ruano, Amaia Moreno Madina. Desirée Panizo López, Rafael Villalba Crucera, Guillermo Martínez Miquel, Borja Jesús Sanjuán Roca, Carlos Crespo Dualde, Blanca Ramírez Belloch, Arturo Brugger De Rojas, Rocío Mormeneo Oliveros, Miguel Blanco Pineda, Teresa Pérez Huertas, José Guillermo Gil García, Rodrigo Climent Pedrosa, Victoria Salguero Rebolledo, Pablo Alba Repullo, Carlota Ramírez Pérez, José Manuel Aznar Cerdán, Emilia Simó García,Ana Asunción Guisan Piñero, Alejandra López Robert, Aroa González Blanco, Aroa Gimeno Muñoz, Francisco Rafael Galán Rubio, Andrea María García Ortiz, Marina Castella Fernandez, Claudia Jover Bernabeu, Pascual Monreal Sanz, Sandra Comes Fernández, Mª Paz Delgado Sanchos, Marina Hernández Ramón, Carla Juliá Fernández, Mónica López Iglesias, Jezabel Tomas Visier, Alberto Armero Estruch, Mar Monter Anduix,Carlos Sáiz Carrión,Elisabet Sanchis Albert, Herminio Serra Martínez, Anna Bueno Girbés, Aila Faus Silvestre,Arian Guillem Sebastià, Laura Caselles Riera, Arantxa Ruiz Ruiz, Enya Aguado Martín, Llivipuma Chaverra, Nuria Iborra Ballester, Jessica Oliva Tomás, Rocío Rodrigo Sousa, José Luis Rodrigo Clemente, Carlos Arias Oliver,Juan Luis Benlliure Salañer, María Teresa Ferrando Toledo, Víctor Lillo Pellicer, Pedro José Paúl Navarrón, Cristina Sánchez Lapetra, Lorena Sanchis Linares, Andrés Vidal Tejedor, Fernando Roig Cervera, Álvaro Sillas Espejo, Laura Rubio Sabater, Sergio Alonso Ávila, Carmen Escamilla Torregrosa, Antonio Fernández Benedito, Cristina Martí Navarro,Asunción Díaz López, Andrada Eliana Tufeanu, Marta Chiva Segrelles, Rut Altur Altur, Mª Maravillas Barranco Alfonso,Alba Barreda Barberà, Alejandro Estruch González, Raquel Guillén Ciscar, Jerahy García García, Carlos Gisbert Blay, Arturo López Peiró, Carlos Martínez Tormo, Rodrigo Gonzalo Muñoz, José Manuel Salas Sampedro, Antonio Gonzalo Vallet Sánchez, Paula Picó, Roberto Pitarch, Inmaculada Monzó, Francisco Javier Ladrón, Álvaro Zabala, Borja Ferrer Pilato, Marien Vila Borja, Marta Ruiz López, Claudia Martínez Moreno, Esther Mont Soria, Giulia Latorre García, Roser Viñoles Tarín, Sofía Nordlund Sierra, Lucia Pérez-Manglano Villalonga, José Miguel Llidó García, Alba Molins Latorre,Paula Moragues Soldevila, Isa Benavent Bonet, Belén Garcia Sachis, Ana Maria Torres, Maria Sydorko, Neus Pérez Monzo, Cristian Mas Font, Francisco Fuentes Ibarra, Tula Juanes Arnal, Vanesa Serrano Ferrandis, Ines Alonso de Armiño, Teresa Giorgeta Blasco, Enrique Estelles Beneyto, Claudia Navarro Pascual, Javier Calatayud García, Mantvydas Bucys, Ruben Si Modjeca, Lisandro Giordani Gonzalez, Marta Requena Montes, Ramón Roda, Miguel Ruiz García, Cristina Esteban Catalá, Iryna Ratseska. Soraya Baltasar Cuevas, Marta Gallardo Andreu, Olena Dyachyshyn, Vicente Boronat Fornes, Ángel Ayala López, Abel Rubio Navarro, Alejandro Guadalajara Crespo, Alejandro Reverte Borras, Henry Valdivia Rocha, Sofia Duart Navarro, Carme Guerola Márquez, Virginia Olivares Tórtola, Rosa Mª de Rojas Galiana, Miguel Crespo Celda, Cristóbal Pino Gómez, Ainhoa Sánchez Navarro, Rosana Franco Altava, Catina Cano Verdia, Mª Carmen Sales Mondrago, Cristina Grimalt Molina, Paloma Moratal Moya, Alba Loreto Peris Rivera, María Jiménez Román, Hizbullah Khan, Francisco López Guillot, Miguel Vaquero Meri, Elisabeth Ruiz Pérez, Cristina Bastida Beltrán, Blanca Bolta Orts, Carla Calabuig Sánchez, Clara Cañero Lois,Carlos Ferrer Mateu, Fernando Fos de la Rubia, Mar Just Catalá, Laura Ortega Cano, Mª Antonia García Juncos, Melina Mata Bernabe, Mª Teresa Mateo Casalí, Mª Amparo Monasor Pérez, Pablo Zurita Varela, Nuria Castillo González, Sandra Nicolás Mascarell, Teresa Bartret García, Laura Madrid Casado, Sara Salvador Lluch, Masun García Boix, Alicia Hernández Rosalén, Inés Escrivá Aranda, Elena Beneyto Soriano, Jorge Montoya Villanueva, Javier Corbí Gradolí, Sonia Pujol Guillot, Silvia Gabarda Navarro, Berta Ramo Alpuente; Claudia Doñate Gallego; Luis Leyva Pardo, Rebeca Mozón Martorell, Arancha Montes Parra,Tatiana López Segura, Ángela Antón Moya,Roberto Gimeno Calleja, Eliseo Gordillo Alvarez, José Alonso Rodríguez Cruz, Luis Andrés Pampillón Ponce, José Armando Flores Sánchez, Yazmín Isolda Álvarez García, Margarita del Carmen Rodríguez Collado, Àngel Aparisi Doménech, Esteban Gaviria, Irene Hernández, Pilar Nagore Lacasa, Georgina Quijada Manganelli
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