¿Cómo se puede querer la Red y el aula a la vez y no estar loco? Un paradigma de relación "cliente‐empresa" como base de un método docente no magistral, con evaluación continuada y sin exámenes

Hoy la información está en La Red. Lo que Google no encuentra, o no existe o es irrelevante. ¿Tiene algún sentido dar clase de espaldas a esta realidad? Aprovechar este magnífico instrumento y hacer que su uso tenga valor formativo para nuestros alumnos parece una opción más útil. La convergencia europea, y también el sentido común, demandan una educación comprometida con la formación. Los contenidos importan, pero también el entrenamiento de habilidades para afrontar el futuro profesional con autonomía, con mayor posibilidad de éxito, tal vez de supervivencia, en un mercado laboral y profesional globalizado donde Europa es ya una isla de bienestar en riesgo. ¿Cómo sumar contenidos con habilidades y reducir horas? ¿Cómo valorar el trabajo fuera del aula? ¿Se puede evaluar con equidad sin exámenes? ¿Cómo repartir los papeles entre profesor y tecnología? Nosotros hemos desarrollado y aplicado un método docente sobre un paradigma “cliente-empresa” como modelo de relación “profesor-alumno”, que se basa en el uso de la Red como fuente de información primaria. El profesor y la relación presencial son centrales, pero con un nuevo sentido. El profesor pasa a ser un consultor experto, un consejero, un tutor, y la relación presencial adquiere así un valor formativo de mayor profundidad. La tecnología no pretende aquí sustituir al profesor ni a la relación presencial con los alumnos. Sólo se utiliza como una herramienta de trabajo real, en la misma forma y para los mismos fines que en una actividad profesional. La experiencia se ha puesto en práctica, hasta la fecha, en dos cursos académicos sucesivos y en dos asignaturas considerablemente dispares. Consideramos que este método tiene aplicabilidad muy general y que aborda la práctica totalidad de los retos y objetivos que se plantean en la adaptación al Espacio Europeo de Educación Superior con resultados muy favorables.Today the information is in the Web. What Google does not find, it does not exist or else it is irrelevant. Does it make any sense to teach ignoring this reality? To take advantage of this magnificent instrument and to make it a formative value for our students seems to be a more useful option. The European convergence, but also the common sense, demands an education compromised with formation. The contents are important, but also the training in abilities to confront the professional future with autonomy, with greater possibility of success, perhaps of survival, in global professional market where Europe is already an island of comfort at risk. How can we keep contents plus abilities in fewer hours? How can we evaluate the work outside the classroom? Is it possible to evaluate with fairness without examinations? How to distribute roles between teacher and technology? We have developed and applied a docent methodology based on a “client‐company” paradigm as a model for the relationship “teacher‐student”. The method is heavily based on the use of the Web as the primary source of information. The professor and the actual relation are central, but with a new sense. The teacher takes the role of an expert consultant, an advisor, a tutor, and the actual relation acquires therefore a formative value of greater depth. Here technology does not replace the teacher nor the actual relation with the students. It is only used like a tool for real work, in the same form and for such aims that in a professional activity. The experience has been put in practice, up to date, in two successive academic courses and two considerably different subjects. This method may have very general applicability and approaches the practical totality of the challenges and objectives of the adaptation to the European Space of Superior Education with very favorable results

Thyroid hormone-mediated activation of the ERK/dual specificity phosphatase 1 pathway augments the apoptosis of GH4C1 cells by down-regulating nuclear factor-κB activity

14 pages, 5 figures.Thyroid hormone (T3) plays a crucial role in processes such as cell proliferation and differentiation, whereas its implication on cellular apoptosis has not been well documented. Here we examined the effect of T3 on the apoptosis of GH4C1 pituitary cells and the mechanisms underlying this effect. We show that T3 produced a significant increase in apoptosis in serum-depleted conditions. This effect was accompanied by a decrease in nuclear factor-kappaB (NF-kappaB)-dependent transcription, IkappaBalpha phosphorylation, translocation of p65/NF-kappaB to the nucleus, phosphorylation, and transactivation. Moreover, these effects were correlated with a T3-induced decrease in the expression of antiapoptotic gene products, such as members of the inhibitor of apoptosis protein and Bcl-2 families. On the other hand, ERK but not c-Jun N-terminal kinase or MAPK p38, was activated upon exposure to T3, and inhibition of ERK alone abrogated T3-mediated apoptosis. In addition, T3 increased the expression of the MAPK phosphatase, dual specificity phosphatase 1 (DUSP1), in an ERK-dependent manner. Interestingly, the suppression of DUSP1 expression abrogated T3-induced inhibition of NF-kappaB-dependent transcription and p65/NF-kappaB translocation to the nucleus, as well as T3-mediated apoptosis. Overall, our results indicate that T3 induces apoptosis in rat pituitary tumor cells by down-regulating NF-kappaB activity through a mechanism dependent on the ERK/DUSP1 pathway.This work was supported by grants from the Fundación Mutua Madrileña (2005X0615), from Fondo de Investigaciones Sanitarias (PI070832), from Ministerio de Educación y Ciencia (BFU2004 3465), from Fondo de Investigaciones Sanitarias (RD06/0020/0036), and the European grant CRESCENDO (FP-018652). A.S.-P. and M.L. are recipients of grants from the Spanish MEC (“Ramón y Cajal” Program).Peer reviewe

Emotional Education within the Tutorial Action in COVID-19’s context

RESUMEN: La Educación Emocional es el proceso educativo que permite potenciar la conciencia emocional y social en la población adolescente. Por ello, es necesario que se trabaje dentro del contexto educativo y en especial dentro de la Acción Tutorial. El objetivo es investigar la atención dedicada a la Educación Emocional en la acción tutorial debido al COVID-19, para posteriormente realizar una propuesta didáctica centrada en las necesidades detectadas. La metodología se basa en un análisis documental del PAT del curso académico 2019/2020 y 2020/2021, en el que se estudia la inclusión de contenidos de Educación Emocional, y en un análisis de la encuesta realizada al profesorado-tutores del mismo centro para conocer su percepción, sensibilización y trabajo sobre la Educación Emocional. Además, se ha realizado una propuesta didáctica para trabajar la Educación Emocional dentro de la Acción Tutorial basándose en las necesidades detectadas. Existen ciertas limitaciones a la investigación debido al tamaño muestral y a la escasez de investigaciones realizadas con anterioridad, pero los resultados obtenidos parecen indicar que, a raíz del COVID-19, el profesorado ha percibido que su alumnado está más sensible emocionalmente y por ello, ha trabajado más la Educación Emocional dentro de la Acción Tutorial.ABSTRACT: Emotional Education is the educational process that allows to enhance emotional and social awareness in the adolescent population. Therefore, it is necessary to work within the educational context and especially within the Tutorial Action. The objective is to investigate the attention dedicated to Emotional Education in the tutorial action due to COVID-19, to later make a didactic proposal focused on the needs detected. The methodology is based on a documentary analysis of the PAT of the academic year 2019/2020 and 2020/2021, in which the inclusion of Emotional Education content is studied, and on an analysis of the survey carried out to the teacher-tutors of the same center to know their perception, awareness and work on Emotional Education. In addition, a didactic proposal has been made to work on Emotional Education within the Tutorial Action based on the needs detected. There are certain limitations to the research due to the sample size and the scarcity of research carried out previously, but the results obtained seem to indicate that, as a result of COVID-19, teachers have perceived that their students are more emotionally sensitive and therefore have worked more on Emotional Education within the Tutorial Action.Máster en Formación del Profesorado de Educación Secundari

Dual inhibition of V600EBRAF and the PI3K/AKT/mTOR pathway cooperates to induce apoptosis in melanoma cells through a MEK-independent mechanism

BRAF is a main oncogene in human melanomas. Here, we show that BRAF depletion by siRNA or inhibition of its activity by treatment with RAF inhibitor Sorafenib induces apoptosis in NPA melanoma cells expressing oncogenic (V600E)BRAF. This effect is mediated through a MEK/ERK-independent mechanism, since treatment with the MEK inhibitor U0126 does not exert any effect. Moreover, we demonstrate that inhibition of the PI3K/AKT/mTOR cascade alone does not increase apoptosis in these cells. However, the blockage of this pathway in cells lacking either BRAF expression or activity cooperates to induce higher levels of apoptosis than those achieved by inhibition of BRAF alone. Consistently, we demonstrate that abrogation of BRAF expression increases AKT and mTOR phosphorylation, suggesting the existence of a compensatory pro-survival mechanism after BRAF depletion. Together, our data provide a rationale for dual targeting of BRAF and PI3K/AKT/mTOR signalling to effectively control melanoma disease

Genomic analysis of the function of the transcription factor gata3 during development of the Mammalian inner ear

We have studied the function of the zinc finger transcription factor gata3 in auditory system development by analysing temporal profiles of gene expression during differentiation of conditionally immortal cell lines derived to model specific auditory cell types and developmental stages. We tested and applied a novel probabilistic method called the gamma Model for Oligonucleotide Signals to analyse hybridization signals from Affymetrix oligonucleotide arrays. Expression levels estimated by this method correlated closely (p<0.0001) across a 10-fold range with those measured by quantitative RT-PCR for a sample of 61 different genes. In an unbiased list of 26 genes whose temporal profiles clustered most closely with that of gata3 in all cell lines, 10 were linked to Insulin-like Growth Factor signalling, including the serine/threonine kinase Akt/PKB. Knock-down of gata3 in vitro was associated with a decrease in expression of genes linked to IGF-signalling, including IGF1, IGF2 and several IGF-binding proteins. It also led to a small decrease in protein levels of the serine-threonine kinase Akt2/PKB beta, a dramatic increase in Akt1/PKB alpha protein and relocation of Akt1/PKB alpha from the nucleus to the cytoplasm. The cyclin-dependent kinase inhibitor p27(kip1), a known target of PKB/Akt, simultaneously decreased. In heterozygous gata3 null mice the expression of gata3 correlated with high levels of activated Akt/PKB. This functional relationship could explain the diverse function of gata3 during development, the hearing loss associated with gata3 heterozygous null mice and the broader symptoms of human patients with Hearing-Deafness-Renal anomaly syndrome

V600e braf inhibition induces cytoprotective autophagy through ampk in thyroid cancer cells

The dysregulation of autophagy is important in the development of many cancers, including thyroid cancer, whereV600E BRAF is a main oncogene. Here, we analyse the effect ofV600E BRAF inhibition on autophagy, the mechanisms involved in this regulation and the role of autophagy in cell survival of thyroid cancer cells. We reveal that the inhibition ofV600E BRAF activity with its specific inhibitor PLX4720 or the depletion of its expression by siRNA induces autophagy in thyroid tumour cells. We show thatV600E BRAF downregulation increases LKB1-AMPK signalling and decreases mTOR activity through a MEK/ERK-dependent mechanism. Moreover, we demonstrate that PLX4720 activates ULK1 and increases autophagy through the activation of the AMPK-ULK1 pathway, but not by the inhibition of mTOR. In addition, we find that autophagy blockade decreases cell viability and sensitize thyroid cancer cells toV600E BRAF inhibition by PLX4720 treatment. Finally, we generate a thyroid xenograft model to demonstrate that autophagy inhibition synergistically enhances the anti-proliferative and pro-apoptotic effects ofV600E BRAF inhibition in vivo. Collectively, we uncover a new role of AMPK in mediating the induction of cytoprotective autophagy byV600E BRAF inhibition. In addition, these data establish a rationale for designing an integrated therapy targetingV600E BRAF and the LKB1-AMPK-ULK1-autophagy axis for the treatment ofV600E BRAF-positive thyroid tumours.This research was supported by grants from the Ministerio de Ciencia, Innovación y Universidades of Spain (SAF 2014-53639-R) and from UAH-Comunidad de Madrid (CAM) (CM/JIN/2019-019

Crosstalk between cAMP and MAP Kinase Signaling in the Regulation of Cell Proliferation

Hormonal stimulation of cyclic adenosine monophosphate (cAMP) and the cAMP-dependent protein kinase PKA regulates cell growth by multiple mechanisms. A hallmark of cAMP is its ability to stimulate cell growth in many cell types while inhibiting cell growth in others. In this review, the cell type-specific effects of cAMP on the mitogen-activated protein (MAP) kinase (also called extracellular signal-regulated kinase, or ERK) cascade and cell proliferation are examined. Two basic themes are discussed. First, the capacity of cAMP for either positive or negative regulation of the ERK cascade accounts for many of the cell type-specific actions of cAMP on cell proliferation. Second, there are several specific mechanisms involved in the inhibition or activation of ERKs by cAMP. Emerging new data suggest that one of these mechanisms might involve the activation of the GTPase Rap1, which can activate or inhibit ERK signaling in a cell-specific manner

Oncogenic Ras, but not V600EB-RAF, protects from cholesterol depletion-induced apoptosis through the PI3K/AKT pathway in colorectal cancer cells

Cholesterol is necessary for proliferation and survival of transformed cells. Here we analyse the effect of cholesterol depletion on apoptosis and the mechanisms underlying this effect in colorectal cancer cells carrying oncogenic Ras or B-V600E-RAF mutations. We show that chronic cholesterol depletion achieved with lipoprotein-deficient serum (LPDS) and 25-hydroxycholesterol (25-HC) treatment results in a significant increase in apoptosis in HT-29 and Colo-205 cells containing the B-V600E-RAF mutation, but not in HCT-116 and LoVo cells harbouring the (G13D)Ras mutation, or BE cells, which possess two mutations, (G13D)Ras and B-G463V-RAF. We also demonstrate that oncogenic Ras protects from apoptosis induced by cholesterol depletion through constitutive activation of the phosphatidylinositol-3 kinase (PI3K)/AKT pathway. The specific activation of the PI3K/AKT pathway by overexpression of the (V12)RasC40 mutant or a constitutively active AKT decreases the LPDS plus 25-HC-induced apoptosis in HT-29 cells, whereas PI3K inhibition or abrogation of AKT expression renders HCT-116 sensitive to cholesterol depletion-induced apoptosis. Moreover, our data show that LPDS plus 25-HC increases the activity of c-Jun N-terminal kinase proteins only in HT-29 cells and that the inhibition of this kinase blocks the apoptosis induced by LPDS plus 25-HC. Finally, we demonstrate that AKT hyperactivation by oncogenic Ras protects from apoptosis, preventing the activation of c-Jun N-terminal kinase by cholesterol depletion. Thus, our data demonstrate that low levels of cholesterol induce apoptosis in colorectal cancer cells without oncogenic Ras mutations. These results reveal a novel molecular characteristic of colon tumours containing Ras or B-RAF mutations and should help in defining new targets for cancer therapy

Biobased polymers derived from itaconic acid bearing clickable groups with potent antibacterial activity and negligible hemolytic activity.

Herein, we report, for the first time, the synthesis of clickable polymers derived from biobased itaconic acid, which was then used for the preparation of novel cationic polymers with antibacterial properties and low hemotoxicity via click chemistry. Itaconic acid (IA) was subjected to chemical modification by incorporating clickable alkyne groups on the carboxylic acids. The resulting monomer with pendant alkyne groups was easily polymerized and copolymerized with dimethyl itaconate (DMI) by radical polymerization. The feed molar ratio of comonomers was varied to precisely tune the content of alkyne groups in the copolymers and the amphiphilic balance. Subsequently, an azide with a thiazole group, which is a component of the vitamin thiamine (B1), was attached onto the polymers by copper-catalyzed azidealkyne cycloaddition (CuAAC) click chemistry leading to triazole linkages. N-Alkylation reactions of the thiazole and triazole groups with methyl and butyl iodides provide the corresponding itaconate derivatives with pendant azolium groups. The copolymers with variable cationic charge densities and hydrophobic/ hydrophilic balances, depending on the comonomer feed ratio, display potent antibacterial activity against Gram-positive bacteria, whereas the activity was almost null against Gram-negative bacteria. Hemotoxicity assays demonstrated that the copolymers exhibited negligible hemolysis and excellent selectivity, more than 1000-fold, for Gram-positive bacteria over human red blood cells.post-print1945 K

PLA and PBAT-based electrospun fibers functionalized with antibacterial bio-based polymers

Antimicrobial fibers based on biodegradable polymers, poly(lactic acid) (PLA), and poly(butylene adipate-co-terephthalate) (PBAT) are prepared by electrospinning. For this purpose, a biodegradable/bio-based polyitaconate containing azoles groups (PTTI) is incorporated at 10&nbsp;wt.% into the electrospinning formulations. The resulting fibers functionalized with azole moieties are uniform and free of beads. Then, the accessible azole groups are subjected to N-alkylation, treatment that provides cationic azolium groups with antibacterial activity at the surface of fibers. The positive charge density, roughness, and wettability of the cationic fibers are evaluated and compared with flat films. It is confirmed that these parameters exert an important effect on the antimicrobial properties, as well as the length of the alkylating agent and the hydrophobicity of the matrix. The quaternized PLA/PTTI fibers exhibit the highest efficiency against the tested bacteria, yielding a 4-Log reduction against S. aureus and 1.7-Log against MRSA. Then, biocompatibility and bioactivity of the fibers are evaluated in terms of adhesion, morphology and viability of fibroblasts. The results show no cytotoxic effect of the samples, however, a cytostatic effect is appreciated, which is ascribed to the strong electrostatic interactions between the positive charge at the fiber surface and the negative charge of the cell membranes