Transcription factor NRF2 uses the Hippo pathway effector TAZ to induce tumorigenesis in glioblastomas

Transcription factor NRF2 orchestrates a cellular defense against oxidative stress and, so far, has been involved in tumor progression by providing a metabolic adaptation to tumorigenic demands and resistance to chemotherapeutics. In this study, we discover that NRF2 also propels tumorigenesis in gliomas and glioblastomas by inducing the expression of the transcriptional co-activator TAZ, a protein of the Hippo signaling pathway that promotes tumor growth. The expression of the genes encoding NRF2 (NFE2L2) and TAZ (WWTR1) showed a positive correlation in 721 gliomas from The Cancer Genome Atlas database. Moreover, NRF2 and TAZ protein levels also correlated in immunohistochemical tissue arrays of glioblastomas. Genetic knock-down of NRF2 decreased, while NRF2 overexpression or chemical activation with sulforaphane, increased TAZ transcript and protein levels. Mechanistically, we identified several NRF2-regulated functional enhancers in the regulatory region of WWTR1. The relevance of the new NRF2/TAZ axis in tumorigenesis was demonstrated in subcutaneous and intracranial grafts. Thus, intracranial inoculation of NRF2-depleted glioma stem cells did not develop tumors as determined by magnetic resonance imaging. Forced TAZ overexpression partly rescued both stem cell growth in neurospheres and tumorigenicity. Hence, NRF2 not only enables tumor cells to be competent to proliferate but it also propels tumorigenesis by activating the TAZ-mediated Hippo transcriptional program.This study was funded by the Spanish Ministry of Economy and Competitiveness (MINECO) under the grant SAF2016-76520-R. ME is recipient of a postdoctoral contract Juan de la Cierva; DL and NRA of a FPU contract of MINECO; MP and RFG of a FPI contracts of Autonomous University of Madrid. RG has been funded by the AECC Scientific Foundation

Teaching biological rhythms in endocrinology: cortisol and wrist temperature. Póster

This work has been developed as part of the Endocrinology and Metabolism student’s laboratory formation from Biology degree at the University of Murcia. Endocrinology and Metabolism is an elective oneterm course that is taught in the fourth year (4.5 ECTS) for "Biosanitary and Biotechnology" intensification. The course focuses on the study of global and intermediary human metabolism and hormonal regulation, both under normal and special situations. It is our objective to get undergraduate students of Endocrinology and Metabolism with the importance of hormonal diurnal fluctuations in endocrine systems through their involvement in an innovative research program. In addition, with the participation of PhD student in this program, we try to improve their skills in innovative teaching. In humans cortisol circadian rhythm peaks in the morning and shows the lowest levels during the midnight. This fluctuation of cortisol plasma level is reflected in saliva, allowing a simple, non invasive and unstressful sample collection. The influence of different factors, exercise, schedule and weekend shifts, on the rhythmic pattern of cortisol has been studied along various years.Campus Mare Nostrum, Universidad Politécnica de Cartagena, Universidad de Murcia, Región de Murci

Innovación del Diseño para el Desarrollo Social

Una labor de síntesis alrededor de la gran temática de este libro que surge a partir de una serie de reflexiones y propuestas encaminadas desde la innovación del diseño para el desarrollo social, refleja una invitación al lector para enunciar a partir de su lectura nuevas discusiones sobre el quehacer del diseño con una perspectiva de innovación para este tipo de desarrollo, es pues este texto una invitación a enunciar nuevos retos y diálogos partiendo de reconocer al desarrollo social como uno de los pilares fundamentales desde la Organización de las Naciones Unidas (ONU) como parte fundamental para garantizar el mejoramiento de la vida de las personas. Desde la disciplina del diseño y retomado como eje para su discusión se pretendería establecer una serie de reflexiones y acciones que permitan atender situaciones para grupos minoritarios y vulnerables, así como apoyar esfuerzos encaminados a mejorar la calidad de vida de los integrantes de grupos y sociedades establecidas y recuperar el patrimonio cultural como parte fundamental de las identidades culturales y por tanto de la historia de la humanidad.A lo largo de la historia, el diseño, en cualquiera de sus manifestaciones, ha estado presente en todos los ámbitos. Se ha convertido en una disciplina que evoluciona al ritmo de las sociedades, que se pone al servicio de las necesidades de mercado pero también de las que requieren un abordaje distinto, observadas desde una mirada que concierne a lo social, entendido éste como lo que se reproduce o se instaura en el colectivo, en el grupo, en las comunidades, en las sociedades como parte significativa de sus cotidianeidades. El Diseño desde esta perspectiva acompaña al ser humano produciendo una significación de los objetos como parte fundamental de sus vidas, que transforma una realidad deseada en una realidad concreta, de aquí la importancia de crear una conciencia social para la praxis laboral de esta disciplina. En este sentido el campo profesional, académico y de investigación del diseño debe ocuparse de crear, difundir y divulgar el quehacer de la misma, manifestando un equilibrio entre conciencia, racionalidad y la realidad. Desde el contexto planteado, la Universidad Autónoma del Estado de México, a través de su Facultad de Arquitectura y Diseño presenta en esta obra una serie de reflexiones en torno al papel que desempeña el diseño humanístico, científico y tecnológico desde un enfoque de vanguardia e innovación para el desarrollo social, como resultado de la experiencia vertida en el Coloquio Internacional de Diseño que organiza éste año este espacio académico, en donde cada una de las aportaciones refleja la experiencia de cada uno de sus participantes; con base en ello, el presente libro integrado por una compilación de trabajos ofrece descripciones, análisis y propuestas que contribuyen a la solución de problemas procurando un desarrollo social

Bases del metabolismo anaerobio en anfibios anuros / Pilar Mendiola López.

Tesis-Universidad de Murcia.Consulte la tesis en: BCA. GENERAL. ARCHIVO UNIVERSITARIO. TM 3385.Consulte la tesis en: BCA. GENERAL. ARCHIVO UNIVERSITARIO. D 170

Pressurized green liquid extraction of betalains and phenolic compounds from Opuntia stricta var. Dillenii whole fruit: Process optimization and biological activities of green extracts

The Opuntia Stricta var. Dillenii's prickly pears are an underutilized fruits, which provide a great source of betalains (mainly, betacyanins) and phenolic compounds (phenolic acids and flavonoids) that could play an important role in health-promotion. This study focuses on the optimization of process for the green extraction of betalains and phenolic compounds from Opuntia stricta var. Dillenii's whole fruits by Pressurized liquid extraction (PLE), using a response surface methodology (RSM) by a central composite design (CCD) in order to obtain rich extracts in betalains and phenolic compounds with the similar profile of the original one found in O. dillenii fruits (avoiding any degradation of these compounds during the extraction process) with proven biological activities. For PLE optimization, the ethanol volume in water (0–100%, v/v) and the temperature (25–65°C) were selected as independent variables. The identification and quantification of the individual bioactive compounds of the obtained green extracts were done by HPLC-DAD-ESI/MS and HPLC-DAD-ESI/QTOF and their biological activities were determined by in vitro tests, as: the antioxidant activity by the ORAC method and the anti-inflammatory activity by the hyaluronidase inhibition method. Ethanol volume in water (%, v/v) was the variable with most significant (p ≤ 0.05) effect in the target responses (bioactive content and biological activities). The best results were obtained at 50% ethanol in water (v/v) and 25°C temperature (run 10) obtaining extracts with betalains as 2.34 ± 0.18 mg of betanin/g dry weight, 2.51 ± 0.04 mg of 5′´-O-E-sinapoyl-2′-apyosil-phyllocactin/g dry weight, 2.32 ± 0.19 mg of neobetanin/g dry weight and phenolic compounds, 2.08 ± 0.07 mg of piscicid acid/g dry weight and 0.25 ± 0.02 mg of isorhamnetin glucoxyl-rhamnosyl-pentoside (IG2) /g dry weight. The betalain and phenolic profile of the PLE extracts was quite similar to the profile from the conventional extraction, but PLE extraction process enhanced the extraction of some bioactives as neobetanin (39%) andpiscidic acid (124%). All employed PLE process CCD combinations significantly upgrade the in vitro biological activities (antioxidant and anti-inflammatory) of the Opuntia stricta var. Dillenii's PLE green extracts.Author Iván Gómez-López thanks Basque Country Government (Spain) for his pre-doctoral scholarship no. PRE_2019_1_010. We thank Gloria Lobo-Rodrigo (ICIA, Spain) for the provision of Opuntia stricta var. Dillinii whole fruits from Tenerife, Canary Islands, Spain. Also, we thanks to the Spanish Ministry of Sciene and Innovation through project PID2020-118300RB-C21Peer reviewe