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

Indicators of the quality of the foster care

Una de las dificultades en la selección de las familias que se acercan al acogimiento familiar está relacionado con la falta de estudios que pudieran apuntar hacia características necesarias que apoyaran un desarrollo integral y comunitario óptimo del menor acogido y a su vez, en el proceso acogedor ayudar tanto a la familia como al menor para generar y/u optimizar aquellos recursos que permitan la consecución de las mismas. En una muestra de 53 familias que a lo largo tres años acogieron a 80 menores nuestro objetivo fue identificar las características que más habían favorecido el desarrollo del menor. Los resultados subrayan la importancia del establecimiento de vínculos seguros del menor con los acogedores, la integración del menor en la familia acogedora (la aparición de un sentido de pertenencia), la existencia de hijos en el núcleo de convivencia y una percepción de satisfacción con el acogimiento, por parte de la familia acogedora.One of the difficulties in choosing the families who come to foster care is related to the lack of studies that indicate the features needed to support optimal integrated development of children in foster care and also help in the process both the family as the child to generate the necessary resources. The sample consisted of 53 families with 80 children in foster care for three years. The aim was to identify characteristics that allow promote the development of the child. The results underline the importance of establishing secure links between the child and the foster family, the integration of the child in the foster family (the emergence of a sense of belonging), the existence of children in the foster family and a sense of satisfaction with welcoming, by the foster family.peerReviewe

Conductas de riesgo y actitudes relacionadas con la infección por VIH/SIDA en HSH

El objetivo de esta investigación es analizar las conductas sexuales de riesgo y las actitudes para la infección por VIH/SIDA en hombres que tienen sexo con otros hombres (HSH). Se administró la Encuesta Sobre SIDA (Ballester, Gil, y Giménez, 2007) a 202 hombres, 168 homosexuales y 34 bisexuales con edades comprendidas entre 14 y 57 años. Los resultados muestran un alta confianza en el preservativo como método de prevención del VIH (el 75.7% considera que es muy eficaz y el 28.1% muy eficaz); no obstante, el uso sistemático del preservativo es moderado tanto en el coito anal (54.6%) como en el coito vaginal (49.1%) y muy bajo en el sexo oral (6.2%). Hay una baja probabilidad percibida (20.3%) y un miedo moderado (41.3%) de infectarse con VIH. El 20.3% afirman haber consumido alcohol en la última relación sexual mientras que el 5.4% refieren otras drogas. Estos resultados deben tenerse en cuenta en la elaboración de programas de prevención.The aim of this investigation is to analyze sexual risk behaviors and attitudes for HIV/AIDS infection of MSM. The ENSI was administrated to 202 men, 168 homosexuals and 24 bisexuals, from 14 to 57 years. The results show a high confidence in condoms as a method of HIV prevention (75.7% very effective and 28.1% effective); however the systematic use of a condom is moderate in anal intercourse (54.64%) and in vaginal intercourse (49.05%) and very low in oral sex (6.22%). There is a low perceived probability (20.28%) and moderate fear (41.25%) become infected with HIV. 20.3% report having drunk alcohol in the last relationship and 5.4% say other drugs. These results should be considered in the development of prevention programs.peerReviewe

Gender roles and aggressiveness in adolescence

La violencia entre adolescentes y jóvenes es un problema que repercute en su desarrollo biopsicosocial y viene determinado por diversos factores. El binomio sexo-género, ha mostrado una influencia considerable en las conductas agresivas adolescentes. Con el interés de profundizar nuestro conocimiento sobre estas variables, el presente estudio analiza la relación que las categorías de género (masculino, femenino, andrógino o indiferenciado) y sexo (hombre o mujer) tienen sobre la agresividad adolescente. Por este motivo, mediante la adaptación española de Inventario de Rol Sexual de Bem (García-Mina Freire, 2004) y el Cuestionario de Información, Actitudes y Comportamientos relacionados con la Salud (Ballester y Gil, 1999), se analiza la presencia de conductas violentas realizadas por 270 adolescentes de la Comunidad Valenciana, entre 13 y 17 años, así como su auto-identificación con el género. En general, los resultados ratifican la relación entre los rasgos masculinos y una mayor probabilidad de ejercer conductas agresivas. Este resultado, también se obtiene en la mayoría de personas identificadas con el “género indiferenciado”. Por el contrario, se reafirma la mayor preocupación por otras personas, de los y las adolescentes con más rasgos femeninos. Además, estos rasgos femeninos son los que muestran tener una mayor influencia en la realización de conductas agresivas, previniendo su aparición. Así pues, los hallazgos confirman la desigualdad de género en el comportamiento agresivo, asociado al universo masculino e indiferenciado, y proponen un amplio campo de acción para las intervenciones preventivas.Adolescent and Young violence remains a concern which damages their biopsychosocial development and involves several factors. The binomial sex-gender has revealed considerable influence on aggressive behavior among adolescents. In order to study in depth our knowledge about these variables, this study analyzes the relation between gender category (masculinity, feminity, adrogyny or undifferentiated) and sex (men or women) to adolescent aggressiveness. For this purpose, by the Spanish adaptation of Sexual Role Inventory by Bem (García-Mina Freire, 2004) and the Cuestionario de Información, Actitudes y Comportamientos relacionados con la Salud (Ballester y Gil, 1999), we analyze the existence of violent behaviors of 270 adolescents from Comunidad Valenciana, ranging from 13 and 17 years old, as well as their self-identification in gender. In general, the results support the relation between masculine traits and higher probability to develop aggressive behaviors. This result is also obtained by the majority of participants self identified as “undifferentiated gender”. However, participants who have more feminine traits are usually more worried about other people. In addition, these traits have shown more influence on aggressive behaviors, preventing their beginning. Therefore, our findings support the gender inequality about aggressive behavior, associated with masculine and undifferentiated universe, and suggest a broad range of actions for preventive interventions.peerReviewe

Knowledge, attitudes and sexual behavior in adults with intellectual disabilities

En este trabajo se lleva a cabo un estudio exploratorio cuyo objetivo general es analizar el comportamiento sexual, y el nivel de conocimientos y actitudes relativas a las prácticas de sexo seguro en una muestra de personas con discapacidad intelectual para prevenir la violencia sexual hacia este colectivo. La muestra está compuesta por 78 personas (39 hombres y 39 mujeres) con discapacidad intelectual leve o moderada. Los resultados obtenidos mediante una entrevista estructurada indican que en el nivel de conocimientos sobre prácticas sexuales destaca que el 73.1% había mantenido relaciones sexuales, el 87.4% conocían los diferentes tipos de métodos anticonceptivos y el 56.3% confiaba en los profesionales y educadores para tratar temas relativos a la sexualidad. Estos resultados subrayan la necesidad de desarrollar programas de educación afectiva-sexual adecuados a este colectivo.This paper conducts an exploratory study whose overall objective is to analyze sexual behavior, level of knowledge and attitudes about safe sex practices in a sample of people with intellectual disabilities to prevent sexual violence against this group. The sample is composed of 78 people (39 men and 39 women) with a mild or moderate intellectual disability. The results obtained through a structured interview indicate that the level of knowledge about sexual practices highlights that 73.1% had sexual intercourse, 87.4% had knowledge of the different types of contraceptive methods and 56.3% trust the professionals and educators to address sexuality issues. These results underscore the importance of tailoring affective-sexual educations programs for this group.peerReviewe

RNA Binding Protein Regulation and Cross-Talk in the Control of AU-rich mRNA Fate

mRNA metabolism is tightly orchestrated by highly-regulated RNA Binding Proteins (RBPs) that determine mRNA fate, thereby influencing multiple cellular functions across biological contexts. Here, we review the interplay between six well-known RBPs (TTP, AUF-1, KSRP, HuR, TIA-1, and TIAR) that recognize AU-rich elements (AREs) at the 3′ untranslated regions of mRNAs, namely ARE-RBPs. Examples of the links between their cross-regulations and modulation of their targets are analyzed during mRNA processing, turnover, localization, and translational control. Furthermore, ARE recognition can be self-regulated by several factors that lead to the prevalence of one RBP over another. Consequently, we examine the factors that modulate the dynamics of those protein-RNA transient interactions to better understand the final consequences of the regulation mediated by ARE-RBPs. For instance, factors controlling the RBP isoforms, their conformational state or their post-translational modifications (PTMs) can strongly determine the fate of the protein-RNA complexes. Moreover, mRNA specific sequence and secondary structure or subtle environmental changes are also key determinants to take into account. To sum up, the whole understanding of such a fine tuned regulation is a challenge for future research and requires the integration of all the available structural and functional data by in vivo, in vitro and in silico approaches.España, Ministerio de Economía y Competitividad BFU2015-71017-PEspaña, Ministerio de Educación, Cultura y Deporte FPU013/04373, FPU016/0151

Indicators of the quality of the foster care

Una de las dificultades en la selección de las familias que se acercan al acogimiento familiar está relacionado con la falta de estudios que pudieran apuntar hacia características necesarias que apoyaran un desarrollo integral y comunitario óptimo del menor acogido y a su vez, en el proceso acogedor ayudar tanto a la familia como al menor para generar y/u optimizar aquellos recursos que permitan la consecución de las mismas. En una muestra de 53 familias que a lo largo tres años acogieron a 80 menores nuestro objetivo fue identificar las características que más habían favorecido el desarrollo del menor. Los resultados subrayan la importancia del establecimiento de vínculos seguros del menor con los acogedores, la integración del menor en la familia acogedora (la aparición de un sentido de pertenencia), la existencia de hijos en el núcleo de convivencia y una percepción de satisfacción con el acogimiento, por parte de la familia acogedora.One of the difficulties in choosing the families who come to foster care is related to the lack of studies that indicate the features needed to support optimal integrated development of children in foster care and also help in the process both the family as the child to generate the necessary resources. The sample consisted of 53 families with 80 children in foster care for three years. The aim was to identify characteristics that allow promote the development of the child. The results underline the importance of establishing secure links between the child and the foster family, the integration of the child in the foster family (the emergence of a sense of belonging), the existence of children in the foster family and a sense of satisfaction with welcoming, by the foster family.peerReviewe

About identification of features that affect the estimation of citrus harvest

Accurate models for early harvest estimation in citrus production generally involve expensive variables. The goal of this research work was to develop a model to provide early and accurate estimations of harvest using low-cost features. Given the original data may derive from tree measurements, meteorological stations, or satellites, they have varied costs. The studied orchards included tangerines (Citrus reticulata x C. sinensis) and sweet oranges (C. sinensis) located in northeastern Argentina. Machine learning methods combined with different datasets were tested to obtain the most accurate harvest estimation. The final model is based on support vector machines with low-cost variables like species, age, irrigation, red and near-infrared reflectance in February and December, NDVI in December, rain during ripening, and humidity during fruit growth. Highlights: Red and near-infrared reflectance in February and December are helpful values to predict orange harvest. SVM is an efficient method to predict harvest. A ranking method to A ranking-based method has been developed to identify the variables that best predict orange production.  Accurate models for early harvest estimation in citrus production generally involve expensive variables. The goal of this research work was to develop a model to provide early and accurate estimations of harvest using low-cost features. Given the original data may derive from tree measurements, meteorological stations, or satellites, they have varied costs. The studied orchards included tangerines (Citrus reticulata x C. sinensis) and sweet oranges (C. sinensis) located in northeastern Argentina. Machine learning methods combined with different datasets were tested to obtain the most accurate harvest estimation. The final model is based on support vector machines with low-cost variables like species, age, irrigation, red and near-infrared reflectance in February and December, NDVI in December, rain during ripening, and humidity during fruit growth. Highlights: Red and near-infrared reflectance in February and December are helpful values to predict orange harvest. SVM is an efficient method to predict harvest. A ranking method to A ranking-based method has been developed to identify the variables that best predict orange production

Sexualidad en diversidad funcional intelectual: recopilación de los instrumentos de evaluación del equipo Salusex

The sexuality of people with intellectual disabilities (ID) is a controversial issue. Their sexuality is characterised by myths and false beliefs that have restricted their right to achieve the experience of a free sexuality. In some cases, their sexuality was equated with that of children, as asexual people; and in other cases, a lack of control over their impulses was assumed, trying not to awaken their sexual instincts. In 2015, SALUSEX team initiated the study of sexuality in this group with a project, funded by the Ministry of Economy and Competitiveness, related to the quality of life and sequelae of sexual abuse. Taking into consideration the needs detected, this project was followed by another, currently under development, with the aim of developing and analysing the effectiveness of a programme to prevent abuse and improve sexual health. In this project, some psychometric instruments are being developed and validated to collect information about their knowledge, beliefs and experiences in both self-reported and other-reported. The aim of this paper is to present some instruments to assess the sexuality in the field of intellectual functional diversity, developed by Salusex team.La sexualidad de las personas con discapacidad intelectual (DI) ha sido un tema muy controvertido. Su sexualidad ha estado sustentada por una serie de mitos y falsas creencias que, a pesar de carecer de apoyo empírico, han restringido su derecho a conseguir una expresión libre de esta faceta. En unos casos su sexualidad ha sido equiparada a la de los niños, creyendo que eran personas asexuadas; y en otros se les ha presupuesto una ausencia de control sobre sus impulsos, optando por no despertar sus instintos sexuales. El equipo SALUSEX inició el estudio de la sexualidad en este colectivo en el año 2015 con un proyecto financiado por el Ministerio de Economía y Competitividad relacionado con la calidad de vida y las secuelas del abuso sexual. Dadas las carencias y necesidades observadas, a este primer proyecto le siguió otro, actualmente en desarrollo, cuyo objetivo es la elaboración y el análisis de la eficacia de un programa de prevención del abuso y mejora de la salud sexual mediante el cual se están desarrollando y validando instrumentos psicométricos para recoger información sobre sus conocimientos, creencias y experiencias tanto de forma autoinformada como heteroinformada. Así, el presente trabajo tiene como propósito presentar algunos instrumentos para la evaluación de la sexualidad en el ámbito de la diversidad funcional intelectual desarrollados por el equipo Salusex

Conductas de riesgo y actitudes relacionadas con la infección por vih/sida en hsh

The aim of this investigation is to analyze sexual risk behaviors and attitudes for HIV/AIDS infection of MSM. The ENSI was administrated to 202 men, 168 homosexuals and 24 bisexuals, from 14 to 57 years. The results show a high confidence in condoms as a method of HIV prevention (75.7% very effective and 28.1% effective); however the systematic use of a condom is moderate in anal intercourse (54.64%) and in vaginal intercourse (49.05%) and very low in oral sex (6.22%). There is a low perceived probability (20.28%) and moderate fear (41.25%) become infected with HIV. 20.3% report having drunk alcohol in the last relationship and 5.4% say other drugs. These results should be considered in the development of prevention programs.El objetivo de esta investigación es analizar las conductas sexuales de riesgo y las actitudes para la infección por VIH/SIDA en hombres que tienen sexo con otros hombres (HSH). Se administró la Encuesta Sobre SIDA (Ballester, Gil, y Giménez, 2007) a 202 hombres, 168 homosexuales y 34 bisexuales con edades comprendidas entre 14 y 57 años. Los resultados muestran un alta confianza en el preservativo como método de prevención del VIH (el 75.7% considera que es muy eficaz y el 28.1% muy eficaz); no obstante, el uso sistemático del preservativo es moderado tanto en el coito anal (54.6%) como en el coito vaginal (49.1%) y muy bajo en el sexo oral (6.2%). Hay una baja probabilidad percibida (20.3%) y un miedo moderado (41.3%) de infectarse con VIH. El 20.3% afirman haber consumido alcohol en la última relación sexual mientras que el 5.4% refieren otras drogas. Estos resultados deben tenerse en cuenta en la elaboración de programas de prevención