Looking for the five continents…and some other one!

RESUMEN: Este Trabajo Fin de Grado utiliza el cine como recurso didáctico significativo en Educación Infantil, para realizar un viaje por los cinco continentes y alguno más. Con este fin, recurriré a la visualización de películas de animación acorde a la edad de los niños. Se parte de una breve introducción y justificación sobre el cine como herramienta de trabajo en el aula. Para entender la importancia de este recurso, he realizado una fundamentación teórica que muestra las múltiples ventajas de su uso desde edades tempranas. Por ende, durante la segunda parte del presente trabajo, se propone una unidad didáctica utilizando el cine, con la meta común de enriquecer el proceso de enseñanza-aprendizaje del alumnado. De esta manera se presentan una serie de actividades para las cuales se han especificado unos objetivos, una temporalización, recursos y los instrumentos de evaluación con respecto a ella.ABSTRACT: This dissertation uses the cinema as a significant educational resource in pre-school education, in order to travel through the five continents and then some. With this in mind, I will resort to the display of animated films according to the children's ages. It starts off with a brief introduction and a justification for the use of the cinema as a tool in the classroom. In order to understand the importance of this resource, I have conducted a theoretical basis which shows the multiple advantages of its use from very young ages. Therefore, a teaching unit which uses the cinema is suggested throughout the second part, with the shared goal to enrich the students’ teaching-learning process. In this way, a series of activities with specific objectives, timing, resources and assessment tools are presented accordingly.Grado en Magisterio en Educación Infanti

Fitoterapia como coadyuvante en el tratamiento de la obesidad

La obesidad es uno de los problemas de salud más importantes a nivel mundial debido a su relación con numerosas patologías como la diabetes mellitus tipo 2, la hipertensión y el aumento importante en el riesgo cardiovascular. La base del tratamiento es la dieta y el ejercicio físico, pero en muchos casos no es sufi ciente y es necesario combinarlo con tratamiento farmacológico. Recientemente se ha retirado sibutramina del mercado por lo que sólo se dispone de orlistat, que no está exento de contraindicaciones y efectos secundarios. Ante esta situación, se ha vuelto a retomar el tratamiento fi toterápico, aunque, en muchas ocasiones, con numerosas dudas. Esta revisión pretende aportar la información necesaria sobre las principales plantas utilizadas en este tratamiento

Cyclophilins A, B, and C Role in Human T Lymphocytes Upon Inflammatory Conditions

Cyclophilins (Cyps) are a group of peptidyl-prolyl cis/trans isomerases that play crucial roles in regulatory mechanisms of cellular physiology and pathology in several inflammatory conditions. Their receptor, CD147, also participates in the development and progression of the inflammatory response. Nevertheless, the main function of Cyps and their receptor are yet to be deciphered. The release of CypA and the expression of the CD147 receptor in activated T lymphocytes were already described, however, no data are available about other Cyps in these cells. Therefore, in the present work intra and extracellular CypA, B and C levels were measured followed by induced inflammatory conditions. After activation of T lymphocytes by incubation with concanavalin A, both intra and extracellular Cyps levels and the CD147 membrane receptor expression were increased leading to cell migration towards circulating CypA and CypB as chemoattractants. When CypA was modulated by natural and synthetic compounds, the inflammatory cascade was avoided including T cell migration. Our results strengthen the relationship between CypA, B, and C, their receptor, and the inflammatory process in human T lymphocytes, associating CypC with these cells for the first timeThe research leading to these results has received funding from the following FEDER cofunded-grants. From Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia, Spain, 2017 GRC GI-1682 (ED431C 2017/01). From CDTI and Technological Funds, supported by Ministerio de Economía, Industria y Competitividad, Spain, ISCIII/PI19/01248, ISCIII/PI19/00879. In European Union, Interreg AlertoxNet EAPA-317-2016, Interreg Agritox EAPA-998-2018, and H2020 778069-EMERTOX. SG was supported by a fellowship from FIDIS, SpainS

Caniferolide A, a Macrolide from Streptomyces caniferus, Attenuates Neuroinflammation, Oxidative Stress, Amyloid-Beta, and Tau Pathology in Vitro

The macrolide caniferolide A was isolated from extracts of a culture of the marine-derived actinomyceteStreptomyces caniferus, and its ability to ameliorate Alzheimer’s disease (AD) hallmarks was determined. The compound reducedneuroinflammatory markers in BV2 microglial cells activated with lipopolysaccharide (LPS), being able to block NFκB-p65translocation to the nucleus and to activate the Nrf2 pathway. It also produced a decrease in pro-inflammatory cytokines (IL-1β,IL-6, and TNF-α), reactive oxygen species (ROS) and nitric oxide release and inhibited iNOS, JNK, and p38 activities.Moreover, the compound blocked BACE1 activity and attenuated Aβ-activation of microglia by drastically diminishing ROSlevels. The phosphorylated state of the tau protein was evaluated in SH-SY5Y tau441 cells. Caniferolide A reduced Thr212 andSer214 phosphorylation by targeting p38 and JNK MAPK kinases. On the other side, the antioxidant properties of themacrolide were determined in an oxidative stress model with SH-SY5Y cells treated with H2O2. The compound diminishedROS levels and increased cell viability and GSH content by activating the nuclear factor Nrf2. Finally, the neuroprotectiveability of the compound was confirmed in two trans-well coculture systems with activated BV2 cells (both with LPS and Aβ)and wild type and transfected SH-SY5Y cells. The addition of caniferolide A to microglial cells produced a significant increase inthe survival of neuroblastoma in both cases. These results indicate that the compound is able to target many pathologicalmarkers of AD, suggesting that caniferolide A could be an interesting drug lead for a polypharmacological approach to theillnessThe research leading to these results has received funding from the following FEDER cofunded-grants, Consellería de Cultura, Educación e Ordenación Universitaria Xunta de Galicia, 2017 GRC GI-1682 (ED431C 2017/01); CDTI and Technological Funds, supported by Ministerio de Economía, Industria y Competitividad, AGL2014-58210-R, AGL2016-78728-R (AEI/FEDER, UE), ISCIII/PI16/01830, RTC-2016-5507-2, and ITC-20161072; and European Union POCTEP 0161-Nanoeaters-1-E-1, Interreg AlertoxNet EAPA-317-2016, Interreg Agritox EAPA-998-2018, H2020 778069-EMERTOX, and FP7 PharmaSea (Grant Agreement 312184).This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular pharmaceutics, copyright © 2019 American Chemical Society, after peer review and technical editing by the publisher.S

Streptocyclinones A and B ameliorate Alzheimer's disease pathological processes in vitro

Alzheimer's disease (AD) is a pathology characterized by the abnormal accumulation of amyloid-beta (Aβ) and hyperphosphorylated tau. Oxidative stress and neuroinflammation are also strongly related to this disease. The ability of two new glycosylated angucyclinones, streptocyclinones A and B (1 and 2), isolated from Streptomyces sp to improve AD hallmarks was evaluated. Compounds were able to protect SH-SY5Y neuroblastoma cells from H2O2-induced oxidative injury by activating the nuclear factor E2-related factor (Nrf2). Their capacity to modulate neuroinflammation was tested in lipopolysaccharide-activated BV2 microglial cells. Compounds reduced the release of pro-inflammatory factors, inhibited the activation of NFκB and mitogen activated kinases (MAPK), and induced the translocation of Nrf2 to the nucleus of microglial cells. A trans-well co-culture was established to determine the effect of microglia treated with streptocyclinones on the survival of SH-SY5Y cells. The cell viability of neuroblastoma cells increased when the compounds were added to BV2 cells. SH-SY5Y-TMHT441 cells were used to determine the effect of compounds on tau phosphorylation. Both compounds reduced tau hyperphophorylation by targeting MAPK kinases. Moreover, streptocyclinone B (2) was able to inhibit the activity of β-secretase 1 and decrease the release of reactive oxygen species in BV2 cells stimulated with Aβ. With the same co-culture trans-well system, the treatment of Aβ-stimulated microglia with compound 2 augmented the viability of SH-SY5Y-TMHT441 cells. The results presented in this work provide evidences of the multitarget activities displayed by these new Streptomyces compounds, making them good candidates for further studies in the treatment of ADThe research leading to these results has received funding from the following FEDER cofunded-grants. From Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia, 2017 GRC GI-1682 (ED431C 2017/01). From CDTI and Technological Funds, supported by Ministerio de Economía, Industria y Competitividad, AGL2014-58210-R, AGL2016-78728-R (AEI/FEDER, UE), ISCIII/PI16/01830 and RTC-2016-5507-2, ITC-20161072. From European Union POCTEP 0161-Nanoeaters -1-E-1, Interreg AlertoxNet EAPA-317-2016, H2020 778069-EMERTOX and FP7 PharmaSea (Grant Agreement 312184).S

Crambescidin-816 Acts as a Fungicidal with More Potency than Crambescidin-800 and -830, Inducing Cell Cycle Arrest, Increased Cell Size and Apoptosis in Saccharomyces cerevisiae

In this paper, we show the effect of crambescidin-816, -800, and -830 on Saccharomyces cerevisiae viability. We determined that, of the three molecules tested, crambescidin-816 was the most potent. Based on this result, we continued by determining the effect of crambescidin-816 on the cell cycle of this yeast. The compound induced cell cycle arrest in G2/M followed by an increase in cell DNA content and size. When the type of cell death was analyzed, we observed that crambescidin-816 induced apoptosis. The antifungal effect indicates that crambescidins, and mostly crambescidin-816, could serve as a lead compound to fight fungal infectionsThe research leading to these results has received funding from the following FEDER cofunded-grants: From Ministerio de Ciencia y Tecnología, Spain: AGL2009-13581-CO2-01, AGL2012-40485-CO2-01. From Xunta de Galicia, Spain: 10PXIB261254 PR. From the European Union’s Seventh Framework Programme managed by REA—Research Executive Agency (FP7/2007-2013) under grant agreement Nos. 211326—CP (CONffIDENCE), 265896 BAMMBO, 265409 µAQUA, and 262649 BEADS, 315285 Ciguatools and 312184 PharmaSea. From the Atlantic Area Programme (Interreg IVB Trans-national): 2009-1/117 PharmatlanticS

Gracilin A Derivatives Target Early Events in Alzheimer’s Disease: inVitro Effects on Neuroinflammation and Oxidative Stress

The search for compounds capable of targeting early pathological changes of Alzheimer̀s disease (AD), such as oxidative stress and neuroinflammation, is an important challenge. Gracilin A derivatives were recently synthesized, using a pharmacophore-directed retrosynthesis (PDR) strategy, and found to possess potent neuroprotective effects. In this work, the previously described derivatives 1–7 which demonstrated mitochondrial-mediated, antioxidant effects were chosen for further study. The ability of compounds to modulate the expression of antioxidant genes (CAT, GPx, SODs, and Nrf2) was determined in SH-SY5Y cells, and the simplified derivatives 2 and 3 were found to be the most effective. The anti-neuroinflammatory properties of all derivatives were assessed in BV2 microglial cells activated with lipopolysaccharide (LPS). Several derivatives decreased the release of cytokines (Il-1β, IL-6, GM-CSF, and TNF-α) and other damaging molecules (ROS, NO) and also regulated the translocation of Nrf2 and NFκB, and reduced p38 activation. These protective effects were confirmed in a trans-well coculture with BV2 and SH-SY5Y cells and several derivatives increased SH-SY5Y survival. This present work demonstrates the neuroprotective properties of gracilin A derivatives, making them promising candidate drugs for AD. Particularly, derivatives 2 and 3 showed the greatest potential as lead compounds for further developmentThe research leading to these results has received funding fromthe following FEDER cofunded-grants. From Consellería de Cultura, Educación e Ordenación Universitaria Xunta de Galicia, 2017 GRC GI-1682 (ED431C 2017/01). From CDTI and Technological Funds, supported by Ministerio de Economía, Industria y Competitividad, AGL2014-58210-R, AGL2016-78728-R (AEI/FEDER, UE), ISCIII/PI16/01830 and RTC-2016-5507-2, ITC-20161072. From European Union POCTEP 0161-Nanoeaters−1-E-1, Interreg AlertoxNet EAPA-317-2016, Interreg Agritox EAPA-998-2018 and H2020 778069-EMERTOX. Support from NIH (R37GM052964 to D.R.) and the Robert A. Welch Foundation (AA-1280 to D.R.) is also gratefully acknowledged.This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Chemical neuroscience, copyright © 2019 American Chemical Society, after peer review and technical editing by the publisher.S

The hidden microbial ecosystem in the perennial ice from a Pyrenean ice cave.

Over the last years, perennial ice deposits located within caves have awakened interest as places to study microbial communities since they represent unique cryospheric archives of climate change. Since the beginning of the twentieth century, the temperature has gradually increased, and it is estimated that by the end of this century the increase in average temperature could be around 4.0°C. In this context of global warming the ice deposits of the Pyrenean caves are undergoing a significant regression. Among this type of caves, that on the Cotiella Massif in the Southern Pyrenees is one of the southernmost studied in Europe. These types of caves house microbial communities which have so far been barely explored, and therefore their study is necessary. In this work, the microbial communities of the Pyrenean ice cave A294 were identified using metabarcoding techniques. In addition, research work was carried out to analyze how the age and composition of the ice affect the composition of the bacterial and microeukaryotic populations. Finally, the in vivo effect of climate change on the cellular machinery that allow microorganisms to live with increasing temperatures has been studied using proteomic techniques

The association of bacterial C9-based TTX-like compounds with Prorocentrum minimum opens new uncertainties about shellfish seafood safety

In 2012, Tetrodotoxin (TTX) was identified in mussels and linked to the presence of Prorocentrum minimum (P. minimum) in Greece. The connexion between TTX and P. minimum was further studied in this paper. First, the presence of TTX-producer bacteria, Vibrio and Pseudomonas spp, was confirmed in Greek mussels. In addition these samples showed high activity as inhibitors of sodium currents (INa). P. minimum was before associated with neurotoxic symptoms, however, the nature and structure of toxins produced by this dinoflagellate remains unknown. Three P. minimum strains, ccmp1529, ccmp2811 and ccmp2956, growing in different conditions of temperature, salinity and light were used to study the production of toxic compounds. Electrophysiological assays showed no effect of ccmp2811 strain on INa, while ccmp1529 and ccmp2956 strains were able to significantly reduce INa in the same way as TTX. In these samples two new compounds, m/z 265 and m/z 308, were identified and characterized by liquid chromatography tandem high-resolution mass spectrometry. Besides, two TTX-related bacteria, Roseobacter and Vibrio sp, were observed. These results show for the first time that P. minimum produce TTX-like compounds with a similar ion pattern and C9-base to TTX analogues and with the same effect on INaInés Rodríguez is supported by a fellowship from Subprograma de Formación de Personal Investigador MINECO (AGL2012-40185-CO2-01), Spain. The research leading to these results has received funding from the following FEDER cofunded-grants. From CDTI and Technological Funds, supported by Ministerio de Economía y Competitividad, AGL2012-40185-CO2-01, AGL2014-58210-R, and Consellería de Cultura, Educación e Ordenación Universitaria, GRC2013-016. From CDTI under ISIP Programme, Spain, IDI-20130304 APTAFOOD. From the European Union’s Seventh Framework Programme managed by REA – Research Executive Agency (FP7/2007-2013) under grant agreement 312184 PHARMASEA.S

Simplified immunosuppressive and neuroprotective agents based on gracilin A

The architecture and bioactivity of natural products frequently serve as embarkation points for the exploration of biologically relevant chemical space. Total synthesis followed by derivative synthesis has historically enabled a deeper understanding of structure–activity relationships. However, synthetic strategies towards a natural product are not always guided by hypotheses regarding the structural features required for bioactivity. Here, we report an approach to natural product total synthesis that we term ‘pharmacophore-directed retrosynthesis’. A hypothesized, pharmacophore of a natural product is selected as an early synthetic target and this dictates the retrosynthetic analysis. In an ideal application, sequential increases in the structural complexity of this minimal structure enable development of a structure–activity relationship profile throughout the course of the total synthesis effort. This approach enables the identification of simpler congeners retaining bioactivity at a much earlier stage of a synthetic effort, as demonstrated here for the spongiane diterpenoid, gracilin A, leading to simplified derivatives with potent neuroprotective and immunosuppressive activityThe authors acknowledge support from the NIH (R37 GM052964 to D.R.), NSF (CHE1800411, to D.R.) the Robert A. Welch Foundation (AA-1280 to D.R.), FEDER co-funded grants from CONSELLERIA DE Cultura, EDUCACION e ordenación Universitaria Xunta de Galicia (2017 GRC GI-1682, ED431C 2017/01), CDTI and Technological Funds, supported by Ministerio de Economía, Industria y Competitividad (AGL2014- 58210-R, AGL2016-78728-R, AEI/FEDER, UE) (to L.M.B.), ISCIII/PI1/01830 (to A.A.) and RTC-2016-5507-2 and ITC-20161072, from EU POCTEP 0161-Nanoeaters-1-E-1, Interreg AlertoxNet EAPA-317-2016 and H2020 778069-EMERTOX (to L.M.B.) and from the European Union’s Seventh Framework Programme managed by the Research Executive Agency (FP7/2007-2013 under grant agreement 312184 PHARMASEA to L.M.B. and M.J.). N. Bhuvanesh and J. Reibenspies (Center for X-ray Analysis, TAMU) secured X-ray data and W. Russell (Laboratory for Biological Mass Spectrometry, TAMU) provided mass data. Correspondence and requests for materials should be directed to D. Romo (chemistry) and L. Botana (biology).S