PKD phosphorylation and COP9/Signalosome modulate intracellular Spry2 protein stability

Spry2 is a molecular modulator of tyrosine kinase receptor signaling pathways that has cancer-type-specific effects. Mammalian Spry2 protein undergoes tyrosine and serine phosphorylation in response to growth factor stimulation. Spry2 expression is distinctly altered in various cancer types. Inhibition of the proteasome functionality results in reduced intracellular Spry2 degradation. Using in vitro and in vivo assays, we show that protein kinase D (PKD) phosphorylates Spry2 at serine 112 and interacts in vivo with the C-terminal half of this protein. Importantly, missense mutation of Ser112 decreases the rate of Spry2 intracellular protein degradation. Either knocking down the expression of all three mammalian PKD isoforms or blocking their kinase activity with a specific inhibitor contributes to the stabilization of Spry2 wild-type protein. Downregulation of CSN3, a component of the COP9/Signalosome that binds PKD, significantly increases the half-life of Spry2 wild-type protein but does not affect the stability of a Spry2 after mutating Ser112 to the non-phosphorylatable residue alanine. Our data demonstrate that both PKD and the COP9/Signalosome play a significant role in control of Spry2 intracellular stability and support the consideration of the PKD/COP9 complex as a potential therapeutic target in tumors where Spry2 expression is reduced.JMR-C received grant support from MINECO-FEDER (SAF2016-78852-R), AESI-ISCIII (PI20CIII/00029) and Spanish Association against Cancer (AECC, CGB14143035THOM). ES group was supported by grants from ISCIII-MCUI (FIS PI19/00934), JCyL (SA264P18-UIC-076), Areces Foundation (CIVP19A5942), Solorzano-Barruso Foundation (FS/32–2020) and by ISCIII-CIBERONC (group CB16/12/00352). Funding to AM group was provided by the Agencia Estatal de Investigación (PID2019-104867RB-I00/AEI/10.13039/501100011033) and by ISCIII-CIBERONC (group CB16/12/00273). TI was supported by grant PID2020-115218RB-I00 funded by MCIN/AEI/ 10.13039/501100011033 and by “ERDF A way of making Europe” and by ISCIII-CIBERNED. RB received grant support from AESI-ISCIII (PI20CIII/00019). Finally, DP-J and MY groups were supported by grants 1.012.022 (to DP-J), 1.010.929 and 1.400.002 (both to MY) from Fundación Universidad Alfonso X el Sabio (FUAX). All research co-financed by FEDER funds.S

Valoración de las metodologías y herramientas docentes por el alumnado. Impulso del mentoring para profesores en la enseñanza online y presencial

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¿Necesitamos un asistente virtual para apoyo y formación permanente de profesores, alumnos y egresados en nuestra página web?

Se trata de identificar las necesidades no resueltas y otras cuestiones de interés, y proponer la utilización del asistente virtual como herramienta de apoyo en el acceso, la formación presente y futura, con carácter permanente, al alumno y al profesor; ello supone su utilidad en el momento presente y en el futuro, como herramienta de formación y acceso permanente. La originalidad del Proyecto estriba precisamente en el planteamiento de la incorporación de la asistencia virtual e inteligencia artificial para la asistencia y apoyo a los alumnos y profesores. El uso de la tecnología es cada vez más mayor, y puede revertir en beneficio al alumno desde una perspectiva más amplia de la que un profesor individualmente puede ofrecerle; se lograría así el acceso a la información con una intervención humana mínima, en cualquier momento y en cuestiones generales de amplio espectro, al que cada profesor en su especialidad no llega a abarcar, y los programas voluntarios de mentorías tampoco

Functional interplay between c-Myc and Max in B lymphocyte differentiation.

The Myc family of oncogenic transcription factors regulates myriad cellular functions. Myc proteins contain a basic region/helix-loop-helix/leucine zipper domain that mediates DNA binding and heterodimerization with its partner Max. Among the Myc proteins, c-Myc is the most widely expressed and relevant in primary B lymphocytes. There is evidence suggesting that c-Myc can perform some of its functions in the absence of Max in different cellular contexts. However, the functional in vivo interplay between c-Myc and Max during B lymphocyte differentiation is not well understood. Using in vivo and ex vivo models, we show that while c-Myc requires Max in primary B lymphocytes, several key biological processes, such as cell differentiation and DNA replication, can initially progress without the formation of c-Myc/Max heterodimers. We also describe that B lymphocytes lacking Myc, Max, or both show upregulation of signaling pathways associated with the B-cell receptor. These data suggest that c-Myc/Max heterodimers are not essential for the initiation of a subset of important biological processes in B lymphocytes, but are required for fine-tuning the initial response after activation.We thank the CNB Animal and Flow Cytometry facilities and the Transgenic CNB-CBMSO UAM/CSIC Unit for the generation of maxflox mice. Next-generation sequencing experiments were performed in the Genomics Unit of the CNIC. We thank K McCreath for editing the manuscript. This work was supported by a grant of the Spanish Ministry of Economy and Competitiveness (SAF2014-52398, AEI/FEDER, UE).S

FRAILTOOLS study protocol: a comprehensive validation of frailty assessment tools to screen and diagnose frailty in different clinical and social settings and to provide instruments for integrated care in older adults

Abstract Background Dozens of scales and questionnaires have been used in the detection of frailty; however, a generalized method for its screening and diagnosis is still lacking in clinical settings. FRAILTOOLS´ main objective is to evaluate the usefulness of frailty scales in the detection of frailty in different clinical and social settings, and its integration in management algorithms for the frail older patient. Methods FRAILTOOLS is an observational, longitudinal and prospective study with a follow-up of 6, 12 and 18 months. People older than 75 years old will be recruited from three separate clinical settings (acute geriatric wards, geriatric outpatient clinics and primary care) and one social setting (nursing homes). Exclusion criteria include Mini-mental State Examination < 20 points, and a Barthel index < 90 points, except in nursing home residents (< 40 points). The participants will be recruited in Spain, Italy, France, United Kingdom and Poland. The total sample size will be of 1.940 subjects, 97 subjects in each clinical setting by center. A personal interview with each participant will take place to register data on comorbidity (Charlson Index), functional (SPPB, Barthel and Lawton indexes), cognitive (MMSE) and frailty status (Fried Phenotype, Frailty Trait Scale – short version, SHARE-FI, 35-Items Rockwood Frailty Index, Clinical Frailty Scale, FRAIL scale and Gérontopôle Frailty Screening Tool) in the baseline visit, month 12 and month 18 visit of follow up. At 6 month a phone call will be made to assess whether there have been falls and to check the vital status. Discussion Currently, the usefulness of certain assessment tools in social and clinical settings have not been properly assessed, including their ability to predict the individual risk for different adverse outcomes, which is the main interest in daily practice. The FRAILTOOLS project concentrates on providing screening and diagnostic tools for frailty in those settings where its prevalence is the highest and where efforts in prevention could make a significant change in the trend towards disability. Trial registration Comprehensive validation of frailty assessment tools in older adults in different clinical and social settings (FRAILTOOLS), NCT02637518 (date of registration: 12/18/2015)

Mentoring para la enseñanza online y mixta. Cambios en las metodologías que se han implementado con la nueva docencia. Estudio y puesta en común de las diferentes metodologías y herramientas didácticas entre las áreas. Focus group con alumnos

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Asistencia virtual para apoyo del personal de administración y servicios en nuestra página www.ucm.es

Este proyecto de innovación es continuación de los proyectos de los cursos 2018/2019 y 2019/2020. El proyecto investiga acerca de las cuestiones que la asistencia virtual puede aportar a la universidad. Pese a los esfuerzos destinados a informar a profesores, alumnos y egresados, y personal de administración y servicios, se observan dificultades en el acceso a la información, por desconocimiento de recursos que la UCM tiene disponibles, o por cuestiones relacionadas con el acceso a la misma