Philosophical foundations of participatory democracy in science and technology

En la reflexión contemporánea sobre la ciencia, y especialmente dentro del campo de trabajo que constituyen los estudios sociales de la ciencia y la tecnología o estudios CTS, uno de los debates destacados está vinculado a la pertinencia y peculiaridades de la participación pública en el contexto de la tecnociencia (un marco en el que, a los problemas generales que se asocian con la democracia participativa, habría que añadir la problemática específica del entorno científico-tecnológico). Este trabajo explorará las preguntas generales por el quién, cuándo, de qué manera o dónde participar, a la luz de la respuesta proporcionada a la cuestión más general del por qué hacerlo. En este sentido el trabajo pondrá de manifiesto cómo buena parte del debate contemporáneo ancla sus raíces en la filosofía griega, planteando la necesidad de reconocer explícitamente esta herencia y sus implicaciones en la búsqueda de una solución adecuada a las encrucijadas de la participación en el ámbito de los problemas ambientales o la regulación energética.In contemporary reflection about science, specially in social studies of science (STS studies), one of the most important debates is related to the relevance and peculiarities of public participation in technoscientific matters (a frame where we must add the specific science and technology problems to the more general ones about participatory democracy). This article explores the general questions about who, when, how or where participate, assuming as framework the answer to the most general question about why to do it. In this sense, I will argue that contemporary debate has an important classical Greek philosophy legacy, suggesting the need to recognize this legacy and their implications in order to and adequate answers to the crossroads of citizen participation before cotemporary S&T issues such as those related to energy and the environment

SUMOylation regulates LKB1 localization and its oncogenic activity in liver cancer

BACKGROUND: Even though liver kinase B1 (LKB1) is usually described as a tumor suppressor in a wide variety of tissues, it has been shown that LKB1 aberrant expression is associated with bad prognosis in Hepatocellular Carcinoma (HCC). METHODS: Herein we have overexpressed LKB1 in human hepatoma cells and by using histidine pull-down assay we have investigated the role of the hypoxia-related post-translational modification of Small Ubiquitin-related Modifier (SUMO)ylation in the regulation of LKB1 oncogenic role. Molecular modelling between LKB1 and its interactors, involved in regulation of LKB1 nucleocytoplasmic shuttling and LKB1 activity, was performed. Finally, high affinity SUMO binding entities-based technology were used to validate our findings in a pre-clinical mouse model and in clinical HCC. FINDINGS: We found that in human hepatoma cells under hypoxic stress, LKB1 overexpression increases cell viability and aggressiveness in association with changes in LKB1 cellular localization. Moreover, by using site-directed mutagenesis, we have shown that LKB1 is SUMOylated by SUMO-2 at Lys178 hampering LKB1 nucleocytoplasmic shuttling and fueling hepatoma cell growth. Molecular modelling of SUMO modified LKB1 further confirmed steric impedance between SUMOylated LKB1 and the STe20-Related ADaptor cofactor (STRADα), involved in LKB1 export from the nucleus. Finally, we provide evidence that endogenous LKB1 is modified by SUMO in pre-clinical mouse models of HCC and clinical HCC, where LKB1 SUMOylation is higher in fast growing tumors. INTERPRETATION: Overall, SUMO-2 modification of LKB1 at Lys178 mediates LKB1 cellular localization and its oncogenic role in liver cancer. FUND: This work was supported by grants from NIH (US Department of Health and Human services)-R01AR001576-11A1 (J.M.M and M.L.M-C.), Gobierno Vasco-Departamento de Salud 2013111114 (to M.L.M.-C), ELKARTEK 2016, Departamento de Industria del Gobierno Vasco (to M.L.M.-C), MINECO: SAF2017-87301-R and SAF2014-52097-R integrado en el Plan Estatal de Investigación Cientifica y Técnica y Innovación 2013-2016 cofinanciado con Fondos FEDER (to M.L.M.-C and J.M.M., respectively), BFU2015-71017/BMC MINECO/FEDER, EU (to A.D.Q. and I.D.M.), BIOEF (Basque Foundation for Innovation and Health Research): EITB Maratoia BIO15/CA/014; Instituto de Salud Carlos III:PIE14/00031, integrado en el Plan Estatal de Investigación Cientifica y Técnica y Innovacion 2013-2016 cofinanciado con Fondos FEDER (to M.L.M.-C and J.M.M), Asociación Española contra el Cáncer (T.C.D, P·F-T and M.L.M-C), Daniel Alagille award from EASL (to T.C.D), Fundación Científica de la Asociación Española Contra el Cancer (AECC Scientific Foundation) Rare Tumor Calls 2017 (to M.L.M and M.A), La Caixa Foundation Program (to M.L.M), Programma di Ricerca Regione-Università 2007-2009 and 2011-2012, Regione Emilia-Romagna (to E.V.), Ramón Areces Foundation and the Andalusian Government (BIO-198) (A.D.Q. and I.D.M.), ayudas para apoyar grupos de investigación del sistema Universitario Vasco IT971-16 (P.A.), MINECO:SAF2015-64352-R (P.A.), Institut National du Cancer, FRANCE, INCa grant PLBIO16-251 (M.S.R.), MINECO - BFU2016-76872-R to (E.B.). Work produced with the support of a 2017 Leonardo Grant for Researchers and Cultural Creators, BBVA Foundation (M.V-R). Finally, Ciberehd_ISCIII_MINECO is funded by the Instituto de Salud Carlos III. We thank MINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-0644). Funding sources had no involvement in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication

Cytochrome c signalosome in mitochondria

Cytochrome c delicately tilts the balance between cell life (respiration) and cell death (apoptosis). Whereas cell life is governed by transient electron transfer interactions of cytochrome c inside the mitochondria, the cytoplasmic adducts of cytochrome c that lead to cell death are amazingly stable. Interestingly, the contacts of cytochrome c with its counterparts shift from the area surrounding the heme crevice for the redox complexes to the opposite molecule side when the electron flow is not necessary. The cytochrome c signalosome shows a higher level of regulation by post-translational modifications—nitration and phosphorylation—of the hemeprotein. Understanding protein interfaces, as well as protein modifications, would puzzle the mitochondrial cytochrome c-controlled pathways out and enable the design of novel drugs to silence the action of pro-survival and pro-apoptotic partners of cytochrome c.Spanish Ministry of Science and Innovation BFU2009-07190Andalusian Government BIO198 P08-CVI-387

Mozambikes : a case study of social entrepreneurship through

This dissertation has been prepared within the overall theme of Social Entrepreneurship and Development. It has been developed in case study format beginning with a literature review, followed by the actual case study, teaching notes and final conclusions and future research. The case study analyses Mozambikes, a for-profit social enterprise based in Mozambique, which intends to use bicycles to empower Mozambicans and improve their quality of life. There are two main objectives to this dissertation. The first is for it to be used for teaching classes of social entrepreneurship, social innovation and business strategy. The second is to unveil the real potential of the business model of Mozambikes, and understand whether or not it is sustainable in the long run. For the development of the case study, fieldwork and field research were conducted in person by the author in Maputo, Mozambique. During one month, interviews were made to the founders of Mozambikes, accompanied by visits to the office and factory of the enterprise to better understand its business model. Part of the research, including the relevant theories explored in the Literature Review, was done in Lisbon, Portugal. We can conclude that Mozambikes has real potential to become a social enterprise that is sustainable in the long run and, at the same time, has real impact in the lives of Mozambicans. In order for this to happen, it should broaden its product portfolio while maintaining a good value proposition for corporations. At the same time, it should focus in key partnerships as to expand and give incentive to the use of bicycles in the country, thus increasing the wholesale branch of its business model in Mozambique's main cities.Esta dissertação foi preparada no contexto do tema de Empreendedorismo Social e Desenvolvimento. Foi desenvolvida no formato de Estudo de Caso e é introduzida por uma revisão sobre a literatura relevante, seguida pelo Estudo de Caso, notas para ensinar o Caso no contexto de uma aula e, por ultimo, conclusões e indicações para pesquisas futuras. O Estudo de Caso analisa a Mozambikes, uma empresa social com fins lucrativos baseada em Moçambique, que pretende utilizar bicicletas para melhorar a qualidade de vida dos moçambicanos. Esta dissertação tem dois objectivos principais. O primeiro é que seja usada em aulas de empreendedorismo social, inovação social e estratégia. O segundo é compreender o verdadeiro potencial do modelo de negócio da Mozambikes e concluir se este é ou não sustentável no longo prazo. Para desenvolver o Estudo de Caos, a autora fez pessoalmente trabalho e pesquisa de campo. Durante um mês foram feitas entrevistas aos fundadores da Mozambikes, acompanhadas de visitas aos escritórios e oficina de montagem da empresa, de forma a melhor compreender o modelo de negócio. Parte da pesquisa, incluindo as teorias exploradas na Revisão de Literatura, foi realizada em Lisboa, Portugal. Podemos concluir que a Mozambikes tem um potencial real para se tornar uma empresa social sustentável no longo prazo e, ao mesmo tempo, ter um impacto na vida dos moçambicanos. Para que isto aconteça, a empresa deverá expandir o seu portefólio de produtos mantendo, ao mesmo tempo, uma boa proposta de valor para as empresas. Simultaneamente, deverá focar-se em parcerias-chave de forma a expandir e incentivar o uso de bicicletas no país, aumentando assim o nível de vendas a individuais no país

Cytochrome c: Surfing Off of the Mitochondrial Membrane on the Tops of Complexes III and IV

The proper arrangement of protein components within the respiratory electron transport chain is nowadays a matter of intense debate, since altering it leads to cell aging and other related pathologies. Here, we discuss three current views-the so-called solid, fluid and plasticity models-which describe the organization of the main membrane-embedded mitochondrial protein complexes and the key elements that regulate and/or facilitate supercomplex assembly. The soluble electron carrier cytochrome c has recently emerged as an essential factor in the assembly and function of respiratory supercomplexes. In fact, a 'restricted diffusion pathway' mechanism for electron transfer between complexes III and IV has been proposed based on the secondary, distal binding sites for cytochrome c at its two membrane partners recently discovered. This channeling pathway facilitates the surfing of cytochrome c on both respiratory complexes, thereby tuning the efficiency of oxidative phosphorylation and diminishing the production of reactive oxygen species. The well-documented post-translational modifications of cytochrome c could further contribute to the rapid adjustment of electron flow in response to changing cellular conditions.Spanish Ministry of Economy and Competitiveness (BFU2015-71017/BMC MINECO/FEDER and PGC2018-096049-B-I00 BIO/BMC MICINN/FEDER, EU

Influencia del sistema de evaluación continua en el rendimiento de los alumnos

Desde la implantación del Espacio Europeo de Educación Superior (EEES) en la Universidad española, los esfuerzos en cuanto al diseño e implantación de nuevas metodologías de enseñanza, aprendizaje, y evaluación han sido constantes. Uno de los pilares de este nuevo modelo es la evaluación continua del alumnado. Sin embargo, dada la actual coyuntura, los sistemas diseñados inicialmente han tenido que adaptarse a las condiciones del aula, manteniendo el espíritu inicial. El propósito principal de este trabajo es mostrar los resultados de la adaptación de la metodología docente y el sistema de evaluación, en el marco de una asignatura que requiere un elevado nivel de abstracción y que por lo general resulta, a priori, poco atractiva para el perfil del alumnado de titulaciones informáticas. Este estudio se ha realizado sobre la asignatura Computabilidad a lo largo de tres cursos académicos. Durante cada uno de ellos la metodología docente y el sistema de evaluación se han ido adaptando progresivamente a las necesidades y particularidades de la asignatura y del alumno, logrando mejorar los resultados e incrementar las tasas de Rendimiento, Éxito y Expectativa. También se han estudiado las posibles diferencias en cuanto a estas tasas del curso con docencia en español frente a su equivalente con docencia en inglés.SUMMARY -- During the last years Spanish higher education is involved in the European Higher Education Area (EHEA) which requires new teaching, learning and evaluation methods. One of the keypoint in this new context is the continuous assessment. However, systems designed in advance have been adapted to the current classroom conditions, trying to keep the original spirit. The goal of this paper is the adaptation of the teaching methodology and evaluation system in the context of a course that requires a high level of abstraction and that usually is, a priori, unattractive for the profile of students from computer grades. This study has been conducted on the course computability over three academic years. During each one, teaching methodology and evaluation system have gradually adapted to the needs and characteristics of the course and student, achieving better results and increasing rates of Output, Success and Expectation. In addition, we have also studied the possible differences in these rates with teaching the course in Spanish versus equivalent teaching in English

HuR biological function involves RRM3-mediated dimerization and RNA binding by all three RRMs

HuR/ELAVL1 is an RNA-binding protein involved in differentiation and stress response that acts primarily by stabilizing messenger RNA (mRNA) targets. HuR comprises three RNA recognition motifs (RRMs) where the structure and RNA binding of RRM3 and of full-length HuR remain poorly understood. Here, we report crystal structures of RRM3 free and bound to cognate RNAs. Our structural, NMR and biochemical data show that RRM3 mediates canonical RNA interactions and reveal molecular details of a dimerization interface localized on the α-helical face of RRM3. NMR and SAXS analyses indicate that the three RRMs in full-length HuR are flexibly connected in the absence of RNA, while they adopt a more compact arrangement when bound to RNA. Based on these data and crystal structures of tandem RRM1,2-RNA and our RRM3-RNA complexes, we present a structural model of RNA recognition involving all three RRM domains of full-length HuR. Mutational analysis demonstrates that RRM3 dimerization and RNA binding is required for functional activity of full-length HuR in vitro and to regulate target mRNAs levels in human cells, thus providing a fine-tuning for HuR activity in vivo.España, MINECO BFU2015-71017España, Junta de Andalucía CVI-BIO198; P11-CVI7216 to I.D.M

Centroid-Based Clustering with ab-Divergences

Centroid-based clustering is a widely used technique within unsupervised learning algorithms in many research fields. The success of any centroid-based clustering relies on the choice of the similarity measure under use. In recent years, most studies focused on including several divergence measures in the traditional hard k-means algorithm. In this article, we consider the problem of centroid-based clustering using the family of ab-divergences, which is governed by two parameters, a and b. We propose a new iterative algorithm, ab-k-means, giving closed-form solutions for the computation of the sided centroids. The algorithm can be fine-tuned by means of this pair of values, yielding a wide range of the most frequently used divergences. Moreover, it is guaranteed to converge to local minima for a wide range of values of the pair (a, b). Our theoretical contribution has been validated by several experiments performed with synthetic and real data and exploring the (a, b) plane. The numerical results obtained confirm the quality of the algorithm and its suitability to be used in several practical applications.MINECO TEC2017-82807-

Dimerization model of the C-terminal RNA Recognition Motif of HuR

In PressHuman antigen R (HuR) is a ubiquitous 32kDa protein comprising three RNA Recognition Motifs (RRMs), whose main function is to bind Adenylate and uridylate Rich Elements (AREs) in 3′ UnTranslated Regions (UTRs) of mRNAs. In addition to binding RNA molecules, the third domain (RRM3) is involved in HuR oligomerization and apoptotic signaling. The RRM3 monomer is able to dimerize, with its self-binding affinity being dependent on ionic strength. Here we provide a deeper structural insight into the nature of the encounter complexes leading to the formation of RRM3 dimers by using Brownian Dynamics and Molecular Dynamics. Our computational data show that the initial unspecific encounter follows a downhill pathway until reaching an optimum conformation stabilized by hydrophobic interactions.I.D.-M. wishes to thank the Andalusian Government (P07-CVI-02896, P11-CVI-07216 and BIO198) for financial support.Peer reviewe