Efecto citotóxico de andrografólida en modelos de cáncer de próstata sensibles y resistentes a terapia anti-androgénica

Tesis (Tecnólogo Médico)El cáncer de próstata es la neoplasia que ocupa el segundo lugar en mortalidad en hombres en Chile. Las células de la próstata, tanto benigna como maligna, tienen por característica presentar receptores de andrógenos (AR) que son esenciales para su proliferación y crecimiento. Una de las terapias para combatir el cáncer es la deprivación androgénica, impidiendo así la activación del receptor y por tanto impidiendo la proliferación celular. Pero un alto porcentaje de los pacientes con cáncer metastásico sufre una progresión de la enfermedad denominada resistente a la castración, donde las células tumorales adquieren la capacidad de proliferar en presencia de bajas concentraciones de andrógenos circulantes. La Andrografólida es una lactona diterpenoide derivada de la Andrographis paniculata que se utiliza para el tratamiento de infecciones, como antiinflamatorio y que tiene actividad anticancerígena recientemente conocidas. La andrografólida es capaz de inhibir la acción del AR y también la expresión de este, siendo una nueva droga a estudiar como futuro tratamiento de esta enfermedad. En este estudio comparamos la acción de la andrografólida frente a cultivos celulares de próstata benigna y maligna, ya sea sensible a andrógenos como también recurrentes a la castración. Mediante ensayo de azul de tripan se determinó que la andrografólida afecta diferencialmente a las células benignas de las malignas, y que incluso entre líneas malignas, afecta mayormente a las líneas celulares resistentes a la castración, que son más invasivas y que hasta ahora no tienen un tratamiento resolutivo sino más bien paliativo. En ensayos de citometría de flujo para proliferación y apoptosis se determinó que la andrografólida es capaz de inducir apoptosis y disminuir la proliferación en las distintas líneas celulares, pero este efecto no ocurre en presencia de andrógenos. Esto quiere decir que una posible terapia para combatir el cáncer de próstata con andrografólida por sí sola no tendría efecto, pero que en combinación con la terapia de deprivación de andrógenos, podría resultar en una terapia más efectiva

An extensive search algorithm to find feasible healthy menus for humans.

Promoting healthy lifestyles is nowadays a public priority among most public entities. The ability to design an array of nutritious and appealing diets is very valuable. Menu Planning still presents a challenge which complexity derives from the problems’ many dimensions and the idiosyncrasies of human behavior towards eating. Among the difculties encountered by researchers when facing the Menu Planning Problem, being able of fnding a rich feasible region stands out. We consider it as a system of inequalities to which we try to fnd solutions. We have developed and implemented a two-phase algorithm -that mainly stems from the Randomized Search and the Genetic- that is capable of rapidly fnding an pool of solutions to the system with the aim of properly identifying the feasible region of the underlying problem and proceed to its densifcation. It consists of a hybrid algorithm inspired on a GRASP metaheuristic and a later recombination. First, it generates initial seeds, identifying best candidates and guiding the search to create solutions to the system, thus attempting to verify every inequality. Afterwards, the recombination of diferent promising candidates helps in the densifcation of the feasible region with new solutions. This methodology is an adaptation of other previously used in literature, and that we apply to the MPP. For this, we generated a database of a 227 recipes and 272 ingredients. Applying this methodology to the database, we are able to obtain a pool of feasible (healthy and nutritious) complete menus for a given D number of days.Open Access granted by Universidad de Málaga / CBUA. This work has been partially supported by the Spanish *Ministerio de Ciencia, Innovación y Universidades *(MCIU/AEI/FEDER, UE) with grant ref PID2019-104263RBC42; and Junta de Andalucía with grant refs. P18-RT-1566, (contract ref CI-21-228) UMA18-FEDERJA- 065. Funding for open access charge: Universidad de Málaga / CBU

Butane Dry Reforming Catalyzed by Cobalt Oxide Supported on Ti2AlC MAX Phase

MAX (M(n+1)AX(n)) phases are layered carbides or nitrides with a high thermal and mechanical bulk stability. Recently, it was shown that their surface structure can be modified to form a thin non-stoichiometric oxide layer, which can catalyze the oxidative dehydrogenation of butane. Here, the use of a Ti2AlC MAX phase as a support for cobalt oxide was explored for the dry reforming of butane with CO2, comparing this new catalyst to more traditional materials. The catalyst was active and selective to synthesis gas. Although the surface structure changed during the reaction, the activity remained stable. Under the same conditions, a titania-supported cobalt oxide catalyst gave low activity and stability due to the agglomeration of cobalt oxide particles. The Co3O4/Al(2)O(3)catalyst was active, but the acidic surface led to a faster deactivation. The less acidic surface of the Ti2AlC was better at inhibiting coke formation. Thanks to their thermal stability and acid-base properties, MAX phases are promising supports for CO(2)conversion reactions

Molybdenum Oxide Supported on Ti3AlC2 is an Active Reverse Water−Gas Shift Catalyst

MAX phases are layered ternary carbides or nitrides that are attractive for catalysis applications due to their unusual set of properties. They show high thermal stability like ceramics, but they are also tough, ductile, and good conductors of heat and electricity like metals. Here, we study the potential of the Ti(3)AlC(2 )MAX phase as a support for molybdenum oxide for the reverse water-gas shift (RWGS) reaction, comparing this new catalyst to more traditional materials. The catalyst showed higher turnover frequency values than MoO3/TiO2 and MoO3/Al2O3 catalysts, due to the outstanding electronic properties of the Ti3AlC2 support. We observed a charge transfer effect from the electronically rich Ti3AlC2 MAX phase to the catalyst surface, which in turn enhances the reducibility of MoO3 species during reaction. The redox properties of the MoO3/Ti3AlC2 catalyst improve its RWGS intrinsic activity compared to TiO2- and Al2O3-based catalysts

Transcription factors Sp1 and p73 control the expression of the proapoptotic protein NOXA in the response of testicular embryonal carcinoma cells to cisplatin

Testicular germ cell tumors (TGCTs) are highly responsive to and curable by cisplatin-based chemotherapy even in advanced stages. We have studied the molecular mechanisms involved in the induction of apoptosis in response to cisplatin, and found that proapoptotic Noxa is transcriptionally up-regulated following cisplatin exposure, even in the absence of p53, in NTERA2 cisplatin-sensitive cells but not in 1411HP-resistant cells. Blockade of Noxa reduced the apoptotic response of embryonal carcinoma (EC) NTERA2 cells to cisplatin. A detailed analysis of the Noxa promoter revealed that p73 and Sp1-like factors, Sp1 and KLF6, played key roles in the transcriptional control of this gene. Overexpression of TAp73 induced Noxa whereas the dominant negative isoform ΔNp73, reduced the levels of Noxa after cisplatin exposure in NTERA2 and 2102EP. Interestingly, down-regulation of Sp1 increased Noxa expression in response to cisplatin. However, blockade of KLF6 decreased cisplatin-induced up-regulation of Noxa in EC cell lines. In addition, tissue microarray analyses of TGCTs revealed that expression of Noxa correlates with good clinical prognosis in patients with embryonal carcinoma. Thus, our data show the transcriptional network that regulates Noxa in EC cells, which is key for their apoptotic response to cisplatin-based chemotherapy, and propose Noxa as a predictive factor of therapeutic response

What seems to explain suicidality in Yucatan Mexican young adults? findings from an app-based mental health screening test using the SMART-SCREEN protocol

The relationship between suicidality, depression, anxiety, and well-being was explored in young adults (median age 20.7 years) from the State of Yucatan (Mexico), which has a suicide rate double that of other Mexican states. A cross-sectional study was carried out in 20 universities in Yucatan and 9,366 students were surveyed using validated questionnaires built into a smartphone app, applying partial least squares structural equation models. High suicide risk was assessed in 10.8% of the sample. Clinically relevant depression and anxiety levels were found in 6.6% and 10.5% of the sample, respectively, and 67.8% reported high well-being. Comparably higher levels of suicide risk, depression and anxiety, and lower well-being were found in women, who were also somewhat older than men in our study. Furthermore, path analysis in the structural equation model revealed that depression was the main predictor of suicidal behaviour as well as of higher anxiety levels and lower self-perceived well-being in the total sample and in both genders. Our findings draw attention to the association between suicidality, depression, anxiety, and well-being in Yucatan young adults and gender differences with this regard. Mental health screening via smartphone might be a useful tool to reach large populations and contribute to mental health policies, including regional suicide prevention effortsOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. No funding was received for this stud

CALIFA, the Calar Alto Legacy Integral Field Area survey: III. Second public data release

García-Benito, R. et. al.© ESO, 2015. This paper describes the Second Public Data Release (DR2) of the Calar Alto Legacy Integral Field Area (CALIFA) survey. The data for 200 objects are made public, including the 100 galaxies of the First Public Data Release (DR1). Data were obtained with the integral-field spectrograph PMAS/PPak mounted on the 3.5 m telescope at the Calar Alto observatory. Two different spectral setups are available for each galaxy, (i) a low-resolution V500 setup covering the wavelength range 3745-7500 Å with a spectral resolution of 6.0 Å (FWHM); and (ii) a medium-resolution V1200 setup covering the wavelength range 3650-4840 Å with a spectral resolution of 2.3 Å (FWHM). The sample covers a redshift range between 0.005 and 0.03, with a wide range of properties in the color-magnitude diagram, stellar mass, ionization conditions, and morphological types. All the cubes in the data release were reduced with the latest pipeline, which includes improvedspectrophotometric calibration, spatial registration, and spatial resolution. The spectrophotometric calibration is better than 6% and the median spatial resolution is 2.4. In total, the second data release contains over 1.5 million spectra.R.G.B., R.G.D., and E.P. are supported by the Spanish Ministerio de Ciencia e Innovacion under grant AYA2010-15081. S.Z. is supported by the EU Marie Curie Integration Grant >SteMaGE> Nr. PCIG12-GA-2012-326466 (Call Identifier: FP7-PEOPLE-2012 CIG). J.F.B. acknowledges support from grants AYA2010-21322-C03-02 and AIB-2010-DE-00227 from the Spanish Ministry of Economy and Competitiveness (MINECO), as well as from the FP7 Marie Curie Actions of the European Commission, via the Initial Training Network DAGAL under REA grant agreement number 289313. Support for L.G. is provided by the Ministry of Economy, Development, and Tourism's Millennium Science Initiative through grant IC12009, awarded to The Millennium Institute of Astrophysics, M.A.S.L.G. also acknowledges support by CONICYT through FONDECYT grant 3140566. A.G. acknowledges support from the FP7/2007-2013 under grant agreement n. 267251 (AstroFIt). J.M.G. acknowledges support from the Fundacao para a Ciencia e a Tecnologia (FCT) through the Fellowship SFRH/BPD/66958/2009 from FCT (Portugal) and research grant PTDC/FIS-AST/3214/2012. RAM was funded by the Spanish programme of International Campus of Excellence Moncloa (CEI). J.M.A. acknowledges support from the European Research Council Starting Grant (SEDmorph; P.I. V. Wild). I.M., J.M. and A.d.O. acknowledge the support by the projects AYA2010-15196 from the Spanish Ministerio de Ciencia e Innovacion and TIC 114 and PO08-TIC-3531 from Junta de Andalucia. AMI acknowledges support from Agence Nationale de la Recherche through the STILISM project (ANR-12-BS05-0016-02). M.M. acknowledges financial support from AYA2010-21887-C04-02 from the Ministerio de Economia y Competitividad. P.P. is supported by an FCT Investigador 2013 Contract, funded by FCT/MCTES (Portugal) and POPH/FSE (EC). P.P. acknowledges support by FCT under project FCOMP-01-0124-FEDER-029170 (Reference FCT PTDC/FIS-AST/3214/2012), funded by FCT-MEC (PIDDAC) and FEDER (COMPETE). T.R.L. thanks the support of the Spanish Ministerio de Educacion, Cultura y Deporte by means of the FPU fellowship. PSB acknowledges support from the Ramon y Cajal program, grant ATA2010-21322-C03-02 from the Spanish Ministry of Economy and Competitiveness (MINECO). C.J.W. acknowledges support through the Marie Curie Career Integration Grant 303912. V.W. acknowledges support from the European Research Council Starting Grant (SEDMorph P.I. V. Wild) and European Career Re-integration Grant (Phiz-Ev P.I.V. Wild). Y.A. acknowledges financial support from the Ramon y Cajal programme (RyC-2011-09461) and project AYA2013-47742-C4-3-P, both managed by the Ministerio de Economia y Competitividad, as well as the >Study of Emission-Line Galaxies with Integral-Field Spectroscopy> (SELGIFS) programme, funded by the EU (FP7-PEOPLE-2013-IRSES-612701) within the Marie-Sklodowska-Curie Actions schemePeer Reviewe

Immune synapse instructs epigenomic and transcriptomic functional reprogramming in dendritic cells.

Understanding the fate of dendritic cells (DCs) after productive immune synapses (postsynaptic DCs) with T cells during antigen presentation has been largely neglected in favor of deciphering the nuances of T cell activation and memory generation. Here, we describe that postsynaptic DCs switch their transcriptomic signature, correlating with epigenomic changes including DNA accessibility and histone methylation. We focus on the chemokine receptor Ccr7 as a proof-of-concept gene that is increased in postsynaptic DCs. Consistent with our epigenomic observations, postsynaptic DCs migrate more efficiently toward CCL19 in vitro and display enhanced homing to draining lymph nodes in vivo. This work describes a previously unknown DC population whose transcriptomics, epigenomics, and migratory capacity change in response to their cognate contact with T cells.This study was supported by grant SAF2017-82886-R from the Spanish Ministry of Economy and Competitiveness (MINECO), grant S2017/BMD-3671-INFLAMUNE-CM from the Comunidad de Madrid, a grant from the Ramon Areces Foundation “Ciencias de la Vida y la Salud” (XIX Concurso-2018), a grant from Ayudas Fundacion BBVA a Equipos de Investigacion Cientifica (BIOMEDICINA-2018), the Fundacio Marato TV3 (grant 122/C/2015), “la Caixa” Banking Foundation (HR17-00016), BIOIMID (PIE13/041) from Instituto de Salud Carlos III, CIBER Cardiovascular (CB16/11/00272), and Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III and co-funding by Fondo Europeo de Desarrollo Regional FEDER). D.C.-F. is supported by a Fellowship from “la Caixa” Foundation (LCF/BQ/DR19/11740010). I.F.-D. is supported by a Fellowship from the Spanish Ministry of Science, Innovation, and Universities (FPU15/02539). The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015- 0505). Funding agencies did not intervene in the design of the studies, with no copyright over the study.S

The incorporation of the SDGs in the Technical Architecture and Building plan (2021) of the University of Alcalá

[EN] The Bachelor's degrees of the first round of verifications (2008), have the obligation to review and renew their teaching approaches, since neither the ways of teaching, nor the ways of practicing the profession, nor the technologies are the same in 2021. There is an opportunity to update the contents and the interrelation between them. The Sustainable Development Goals (SDGs) can and should be part of this process of teaching innovation. This is the case of the evolution of the Degree in Science and Technology of Building, to the Degree in Technical Architecture and Building, recently approved (March 2021). The objective of the communication is to present the method followed for the integration of the SDGs in the verification process. The way practiced to determine the goals of each SDG to be incorporated is analyzed. The prioritization of the character of transversality in the planned approach, not as a specific subject but integrated, coordinated, and related between the different subjects in which it is progressively integrated into the degree. Finally, the definitive incorporation procedure to the Plan, its documentary and conceptual reflection, and the implementation forecast, the monitoring and control processes for the 2021/2022 academic year will be discussed.[ES] Las titulaciones de Grado de la primera tanda de verificaciones (2008), tienen la obligación de revisar y renovar sus planteamientos docentes, ya que ni los modos de enseñar, ni los modos de ejercer la profesión, ni las tecnologías son las mismas en 2021. Se presenta una oportunidad de actualización de los contenidos y la interrelación entre ellos. Los Objetivos de Desarrollo Sostenible (ODS) pueden y deben formar parte de este proceso de innovación docente. Es el caso de la evolución del Grado en Ciencia y Tecnología de la Edificación, al Grado de Arquitectura Técnica y Edificación, aprobado recientemente (marzo 2021). El objetivo de la comunicación es presentar el método seguido para la integración de los ODS en el proceso de verificación. Se analiza el modo practicado para determinar las metas de cada ODS a incorporar. La priorización del carácter de transversalidad en el enfoque planificado, no como materia específica sino integrada, coordinada, y relacionada entre las diferentes asignaturas en las que se integra de forma progresiva en la titulación. Por último se comentará el procedimiento de incorporación definitiva al Plan, su reflejo documental y conceptual, y la previsión de implantación, los procesos de seguimientos y control para el curso 2021/2022.Da Casa Martín, F.; Baño Nieva, A.; Vega Ballesteros, JM.; Delgado Conde, I.; Maza Vazquez, F.; Fernandez Tapia, E.; Temiño Vela, J.... (2021). La incorporación de los ODS en el plan de estudios de Arquitectura Técnica y Edificación (2021) de la Universidad de Alcalá. En EDIFICATE. I Congreso de Escuelas de Edificación y Arquitectura Técnica de España. Editorial Universitat Politècnica de València. 409-421. https://doi.org/10.4995/EDIFICATE2021.2021.13543OCS40942

WHODAS 2.0 as a Measure of Severity of Illness: Results of a FLDA Analysis

WHODAS 2.0 is the standard measure of disability promoted by World Health Organization whereas Clinical Global Impression (CGI) is a widely used scale for determining severity of mental illness. Although a close relationship between these two scales would be expected, there are no relevant studies on the topic. In this study, we explore if WHODAS 2.0 can be used for identifying severity of illness measured by CGI using the Fisher Linear Discriminant Analysis (FLDA) and for identifying which individual items of WHODAS 2.0 best predict CGI scores given by clinicians. One hundred and twenty-two patients were assessed with WHODAS 2.0 and CGI during three months in outpatient mental health facilities of four hospitals of Madrid, Spain. Compared with the traditional correction of WHODAS 2.0, FLDA improves accuracy in near 15%, and so, with FLDA WHODAS 2.0 classifying correctly 59.0% of the patients. Furthermore, FLDA identifies item 6.6 (illness effect on personal finances) and item 4.5 (damaged sexual life) as the most important items for clinicians to score the severity of illness