Geologia viatjant : proposta didàctica de treball per projectes programada en 5E

A qui no li agradaria conèixer els indrets més bells i geològicament interessants de la Terra? En aquesta seqüència didàctica us proposo treballar la dinàmica interna i externa de la Terra a partir d'un context de viatges figurats pel món per quinze destinacions diferents. La seqüència, d'un total de nou sessions, està organitzada d'acord amb la metodologia 5E (Enganxa, Explora, Explica, Elabora i Avalua) incloent aprenentatge basat en projectes (ABP) i coavaluació. L'estructura senzilla que segueix vol animar a treballar per projectes a docents que encara no hi tinguin àmplia experiència prèvia, així com ajudar a conèixer el model de programació en 5E.Who wouldn't want to get to know the most beautiful and geologically interesting places on the Earth? This didactic experience will allow you to study the internal and external dynamics of the Earth through a context of travelling to up to fifteen different destinations. The sequence, which includes nine sessions, is organised according to the 5E instructional model (Engage, Explore, Explain, Elaborate, and Evaluate) including project-based learning (PBL) and co-evaluation. The simplicity of this experience aims to engage other teachers to work through PBL, and to contribute to spread the 5E instructional model

Animacions en stop-motion : una oportunitat per aprofundir en el model cineticomolecular de la matèria

El model cineticomolecular és primordial per a la interpretació de diversos fenòmens de la matèria i constitueix una base de l'aprenentatge de la química. Però les partícules no són observables i alguns aspectes del model són complexos d'integrar: per exemple, el moviment de les partícules i els seus canvis amb la temperatura tenen molta importància en el model, però difícilment es descriuen en representacions gràfiques. Per superar aquestes dificultats d'aprenentatge a 2n d'ESO s'ha desenvolupat un projecte basat en la creació de vídeos en stop-motion amb el qual els alumnes aprendran a planificar un guió per a descriure un fenomen (els estats de la matèria, un canvi d'estat, la dilatació...) i a reproduir amb dibuixos i materials manipulatius el model cineticomolecular per tal de representar la interpretació dels processos microscòpics de diversos fenòmens quotidians.Kinetic-molecular theory is the key for interpretation of diverse matter phenomena, and it is the basis of chemical learning. However, particles cannot be seen, and some aspects of the model are difficult to acquire: for instance, particle movement related to temperature is very important in interpretations, but it is hardly represented in student's drawings and explanations. To overcome these learning difficulties at 2nd grade, we developed a project consisting of stop-motion video creation, in which students learn to plan a script to describe a phenomenon (states of the matter, state changes, dilatation...) and to draw and build kinetic-molecular models that represent the microscopic interpretation of diverse common phenomena.El modelo cineticomolecular es esencial para la interpretación de fenómenos diversos de la materia y constituye una base del aprendizaje de la química. Pero las partículas no son observables y algunos aspectos del modelo son complejos de integrar: el movimiento de las partículas y sus cambios con la temperatura tienen mucha importancia en el modelo, pero difícilmente se describen en representaciones graficas. Para superar estas dificultades de aprendizaje a 2o de ESO, se ha desarrollado un proyecto basado en la creación de vídeos en stop-motion, con el qual los alumnos aprenderán a planificar un guion para describir un fenómeno (los estados de la materia, un cambio de estado, la dilatación...) y a reproducir mediante dibujos y materiales manipulativos el modelo cineticomolecular con el fin de representar la interpretación de procesos microscópicos de diversos fenómenos cotidianos

Endothelin-Dependent Vasoconstriction in Human Uterine Artery: Application to Preeclampsia

BACKGROUND: Reduced uteroplacental perfusion, the initiating event in preeclampsia, is associated with enhanced endothelin-1 (ET-1) production which feeds the vasoconstriction of uterine artery. Whether the treatments of preeclampsia were effective on ET-1 induced contraction and could reverse placental ischemia is the question addressed in this study. We investigated the effect of antihypertensive drugs used in preeclampsia and of ET receptor antagonists on the contractile response to ET-1 on human uterine arteries. METHODOLOGY/PRINCIPAL FINDINGS: Experiments were performed, ex vivo, on human uterine artery samples obtained after hysterectomy. We studied variations in isometric tension of arterial rings in response to the vasoconstrictor ET-1 and evaluated the effects of various vasodilators and ET-receptor antagonists on this response. Among antihypertensive drugs, only dihydropyridines were effective in blocking and reversing the ET-1 contractile response. Their efficiency, independent of the concentration of ET-1, was only partial. Hydralazine, alpha-methyldopa and labetalol had no effect on ET-1 induced contraction which is mediated by both ET(A) and ET(B) receptors in uterine artery. ET receptors antagonists, BQ-123 and BQ-788, slightly reduced the amplitude of the response to ET-1. Combination of both antagonists was more efficient, but it was not possible to reverse the maximal ET-1-induced contraction with antagonists used alone or in combination. CONCLUSION: Pharmacological drugs currently used in the context of preeclampsia, do not reverse ET-1 induced contraction. Only dihydropyridines, which partially relax uterine artery previously contracted with ET-1, might offer interesting perspectives to improve placental perfusion

Mitochondrial regulation of citotoxicity induced by amyloid-beta peptides

Peer Reviewe

Geologia viatjant : proposta didàctica de treball per projectes programada en 5E

A qui no li agradaria conèixer els indrets més bells i geològicament interessants de la Terra? En aquesta seqüència didàctica us proposo treballar la dinàmica interna i externa de la Terra a partir d'un context de viatges figurats pel món per quinze destinacions diferents. La seqüència, d'un total de nou sessions, està organitzada d'acord amb la metodologia 5E (Enganxa, Explora, Explica, Elabora i Avalua) incloent aprenentatge basat en projectes (ABP) i coavaluació. L'estructura senzilla que segueix vol animar a treballar per projectes a docents que encara no hi tinguin àmplia experiència prèvia, així com ajudar a conèixer el model de programació en 5E.Who wouldn't want to get to know the most beautiful and geologically interesting places on the Earth? This didactic experience will allow you to study the internal and external dynamics of the Earth through a context of travelling to up to fifteen different destinations. The sequence, which includes nine sessions, is organised according to the 5E instructional model (Engage, Explore, Explain, Elaborate, and Evaluate) including project-based learning (PBL) and co-evaluation. The simplicity of this experience aims to engage other teachers to work through PBL, and to contribute to spread the 5E instructional model

APP/PS1 mice overexpressing SREBP-2 exhibit combined Aß accumulation and tau pathology underlying Alzheimer's disease

El pdf del artículo es la versión post-print.Current evidence indicates that excess brain cholesterol regulates amyloid-β (Aβ) deposition, which in turn can regulate cholesterol homeostasis. Moreover, Aβ neurotoxicity is potentiated, in part, by mitochondrial glutathione (mGSH) depletion. To better understand the relationship between alterations in cholesterol homeostasis and Alzheimer's disease (AD), we generated a triple transgenic mice featuring sterol regulatory element-binding protein-2 (SREBP-2) overexpression in combination with APPswe/PS1ΔE9 mutations (APP/PS1) to examine key biochemical and functional characteristics of AD. Unlike APP/PS1 mice, APP/PS1/SREBP-2 mice exhibited early mitochondrial cholesterol loading and mGSH depletion. Moreover, β-secretase activation and Aβ accumulation, correlating with oxidative damage and neuroinflammation, were accelerated in APP/PS1/SREBP-2 mice compared with APP/PS1 mice. Triple transgenic mice displayed increased synaptotoxicity reflected by loss of synaptophysin and neuronal death, resulting in early object-recognition memory impairment associated with deficits in spatial memory. Interestingly, tau pathology was present in APP/PS1/SREBP-2 mice, manifested by increased tau hyperphosphorylation and cleavage, activation of tau kinases and neurofibrillary tangle (NFT) formation without expression of mutated tau. Importantly, in vivo treatment with the cell permeable GSH ethyl ester, which restored mGSH levels in APP/PS1/SREBP-2 mice, partially prevented the activation of tau kinases, reduced abnormal tau aggregation and Aβ deposition, resulting in attenuated synaptic degeneration. Taken together, these results show that cholesterol-mediated mGSH depletion is a key event in AD progression, accelerating the onset of key neuropathological hallmarks of the disease. Thus, therapeutic approaches to recover mGSH may represent a relevant strategy in the treatment of AD.This work was supported by Plan Nacional de I+ D+I (SAF2010-03923 to A.C. and SAF2009-11417 and SAF2012-34831 to J.C.F-C); by Centro de Investigación Biomédica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD); by Instituto de Salud Carlos III; by Research Center for Liver and Pancreatic Diseases, NIAAA/NIH (P50-AA-11999 to J.C. F-C) and by Marato TV3. E.B.C. has a FPI fellowship from Ministerio de Economía y Competitividad.Peer Reviewe

SREBP-2-mediated cholesterol accumulation regulates beta-amyloid-induced autophapy in APP/PS1/SREBP-2 mice

Comunicación presentada en la Alzheimer's Association 2013 International Conference, celebrada del 13 al 18 de julio de 2013 en Boston (Estados Unidos)Aberrant autophagy in Alzheimer's Disease (AD) is evidenced by a massive build-up of autophagy intermediates, suggesting increased autophagosome formation or defective progression to autophagolysosomes. To date, the exact mechanisms that led to this dysfunction are unknown; however, as similar defects are observed in Niemann-Pick type C1 knockout mice, which accumulate cholesterol in late endosomes/lysosomes, we hypothesize that the impaired cholesterol homeostasis described in AD may play a rolePeer Reviewe

La generación de ratones transgénicos Tg-APP/PS1-SREBP2 como modelo del papel patogénico de colesterol en la enfermedad de Alzheimer (EA)

Trabajo presentado al XXXIII Congreso de la Sociedad Española de Bioquímica y Biología Molecular celebrado en Córdoba del 14 al 17 de septiembre de 2010.El colesterol promueve la síntesis y agregación de péptidos beta-amiloide (Ab). Además, en estudios recientes mostramos un nuevo papel patogénico del colesterol mitocondrial en la EA, estimulando la citotoxicidad de Ab debido a una disminución del glutation mitocondrial (mGSH). Nuestro objetivo fue estudiar el efecto regulador del colesterol en la progresión de la EA, en relación con el estrés de retículo endoplasmático (RE). Para ello, generamos ratones transgénicos Tg-APP/PS1 que sobreexpresan SREBP-2 (Tg-APP/PS-SREBP2) y analizamos a diferentes edades (4, 7, 10 meses) indicadores característicos de la EA. Resultados: Los ratones Tg-APP/PS1-SREBP2 mostraban un incremento de colesterol (total y mitocondrial) y una disminución selectiva del mGSH. Ambas alteraciones eran detectables en ratones Tg-APP/PS1 de 10 meses y se acompañaban de una activación de SREBP2. La frecuencia de animales con elevados niveles de Ab aumentaba con la sobre-expresión de SREBP2. Estas diferencias eran significativas a los 4-7 meses de edad y correlacionaban con una mayor actividad de la enzima gammasecretasa. A partir de los 7 meses los ratones Tg-APP/PS1-SREBP2 mostraban mayor daño oxidativo y neuroinflamación. Además, el incremento de colesterol aceleraba tanto la degeneración sináptica como la muerte neuronal. El análisis de expresión de GADD153, GRP78 y pEIF2a reveló una temprana activación de estrés de RE. Conclusiones: El colesterol potencia el daño neuronal mediado por Ab acelerando la progresión de la EA. La existencia de un estrés de RE temprano, a través de la activación de SREBP2, podría ser el mecanismo responsable del incremento de colesterol detectado en ratones Tg-APP/PS1.Peer Reviewe

Colesterol i mitocondria en la citotoxicitat induïda per beta-amiloide

Trabajo presentado en la Jornada anual: «Senyals implicats en mort cel·lular», celebrada en Barcelona, España, el 18 de junio de 2010Peer Reviewe