Understanding Epigenetics in the Neurodegeneration of Alzheimer's Disease: SAMP8 Mouse Model

Epigenetics is emerging as the missing link among genetic inheritance, environmental influences, and body and brain health status. In the brain, specific changes in nucleic acids or their associated proteins in neurons and glial cells might imprint differential patterns of gene activation that will favor either cognitive enhancement or cognitive loss for more than one generation. Furthermore, derangement of age-related epigenetic signaling is appearing as a significant risk factor for illnesses of aging, including neurodegeneration and Alzheimer's disease (AD). In addition, better knowledge of epigenetic mechanisms might provide hints and clues in the triggering and progression of AD. Intense research in experimental models suggests that molecular interventions for modulating epigenetic mechanisms might have therapeutic applications to promote cognitive maintenance through an advanced age. The SAMP8 mouse is a senescence model with AD traits in which the study of epigenetic alterations may unveil epigenetic therapies against the AD. Keywords: Aging, DNA methylation, epigenetics, histone modification, neurodegeneratio

Synthesis and antitumor activity of mechercharmycin A analogues

Several analogs of the cytotoxic thiopeptide IB-01211 or Mechercharmycin A (1) have been synthetized. The cytotoxicity of 1 and the synthetized analogs was evaluated against a panel of three human tumor cell lines. Thiopeptide 1 and the most active derivatives, 2 and 3c, were chosen for further studies like effects on cell cycle progression and induction of apoptosis. Interestingly, the inhibition of cell division and activation of a programmed cell death by apoptosis was detected

Lamellarin D bioconjugates I: synthesis and cellular internalization of PEG-derivatives

Herein is reported the design and synthesis of poly(ethylene glycol) derivatives of Lamellarin D with the aim of modulating their physicochemical properties, and improving the biological activity. Mono-, di- and tri-PEG conjugates with improved solubility were obtained in 18-57% overall yields from the corresponding partially protected phenolic derivatives of Lamellarin D. Conjugates 1-9 were tested in a panel of three human tumor cell lines (MDA-MB-231 breast, A-549 lung and HT-29 colon) to evaluate their cytotoxicity. Several compounds exhibited enhanced cellular internalization, and more than 85% of the derivatives showed a lower GI50 than Lam-D. Furthermore, cell cycle arrest at G2 phase, and apoptotic cell-death pathways were determined for Lamellarin D and these derivatives

Novel index for quantification of ecosystems effects of fishing as removal of secondary production

Exploited ecosystems are characterised by exports of secondary production from each fished trophic level that reduce the energy available for upper levels at the ecosystem scale, thus impinging on overall secondary production. Depletion in secondary production is proposed here as a proxy for quantifying the ecosystem effects of fishing. Theoretical analysis of trophic web interactions permits the quantification of the ‘loss in production’ and provides an ecological basis for defining a new synthetic index (L index) that takes into account both ecosystem properties (primary production and transfer efficiency) and features of fishing activities (trophic level of catches and primary production required). Quantitative meta-analysis of ecological models, representing 51 exploited ecosystems previously classified as overexploited or sustainably exploited, allows the association of a probability of the ecosystem being sustainably fished with each index value. Moreover, by fixing the reference level for this probability, the index provides a basis for estimating the maximum allowable catches. The L index is applied here to several ecosystems worldwide using landings data and ecological models, providing quantification of the disruption of energy flows for ecosystems subjected to different types and levels of fishing pressure. Its application to outputs of calibrated dynamic models enables the evaluation of sustainability of fisheries in past and future scenarios of alternative fisheries management policies. Results highlight the usefulness of this index for quantifying the impacts of fishing and providing directional advice for fisheries management. Thus, the L index may be used to support ecosystem-based management of fisheries

High-Fat and Resveratrol Supplemented Diets Modulate Adenosine Receptors in the Cerebral Cortex of C57BL/6J and SAMP8 Mice

Neurodegenerative disorders are devastating diseases in which aging is a major risk factor. High-fat diet (HFD) seems to contribute to cognition deterioration, but the underlying mechanisms are poorly understood. Moreover, resveratrol (RSV) has been reported to counteract the loss of cognition associated with age. Our study aimed to investigate whether the adenosinergic system and plasma membrane cholesterol are modulated by HFD and RSV in the cerebral cortex of C57BL/6J and SAMP8 mice. Results show that HFD induced increased A1R and A2AR densities in C57BL/6J, whereas this remained unchanged in SAMP8. Higher activity of 50 -Nucleotidase was found as a common effect induced by HFD in both mice strains. Furthermore, the effect of HFD and RSV on A2BR density was different depending on the mouse strain. RSV did not clearly counteract the HFD-induced effects on the adenosinergic system. Besides, no changes in free-cholesterol levels were detected in the plasma membrane of cerebral cortex in both strains. Taken together, our data suggest a different modulation of adenosine receptors depending on the mouse strain, not related to changes in plasma membrane cholesterol conten

Maternal Resveratrol Supplementation Prevents Cognitive Decline in Senescent Mice Offspring

A variety of environmental factors contribute significantly to age-related cognitive decline and memory impairment in Alzheimer's Disease (AD) and other neurodegenerative diseases. Nutrition can alter epigenetics, improving health outcomes, which can be transmitted across generations; this process is called epigenetic inheritance. We investigate the beneficial effects of maternal resveratrol supplementation in the direct exposed F1 generation and the transgenerational F2 generation. The offspring was generated from females Senescence Accelerated Mouse-Prone (SAMP8) fed a resveratrol-enriched diet for two months prior to mating. Object novel recognition and Morris Water Maze (MWM) demonstrated improvements in cognition in the 6-month-old F1 and F2 generations from resveratrol fed mothers. A significant increase in global DNA methylation with a decrease in hydroxymethylation in F1 and F2 were found. Accordingly, Dnmt3a/b and Tet2 gene expression changed. Methylation levels of Nrf2 and NF-kβ genes promoters raised in offspring, inducing changes in target genes expression, as well as hydrogen peroxide levels. Offspring that resulted from a resveratrol fed mother showed increase AMPKα activation, mTOR inhibition, and an increase in Pgc-1α gene expression and Beclin-1 protein levels. Endoplasmic reticulum stress sensors were found changed both in F1 and F2 generations. Overall, our results demonstrated that maternal resveratrol supplementation could prevent cognitive impairment in the SAMP8 mice offspring through epigenetic changes and cell signaling pathways. Keywords: cognitive decline; epigenetics; epigenetic inheritance; methylation; Nrf2; NF-κB; oxidative stress; inflammation; resveratrol; SAMP

Spread of the alien bleak Alburnus alburnus (Linnaeus, 1758) (Actinopterygii, Cyprinidae) in the Iberian Peninsula: the role of reservoirs

Desde su aparición en un afluente de la cuenca del Ebro en 1992, el alburno Alburnus alburnus se ha expandido en gran parte de la península Ibérica. El presente trabajo aporta nueva información sobre su expansión (basada en el muestreo de 598 localidades mediante pesca eléctrica). Se facilita información detallada sobre su actual distribución en la cuenca del Ebro y en cuencas al este de los Pirineos, así como nuevas citas de tres grandes cuencas hidrográficas. De acuerdo a su actual distribución en la península Ibérica, el alburno habita en simpatría con 15 especies endémicas (el 58% del total de endemismos ibéricos). Se analiza la posible amenaza que el alburno representa para la ictiofauna ibérica, examinando los factores causantes de su rápida expansión, en especial el papel de los embalses

Behaviour and cognitive changes correlated with hippocampal neuroinflammaging and neuronal markers in female SAMP8, a model of accelerated senescence

Senescence accelerated mice P8 (SAMP8) is a phenotypic model of age, characterized by deficits in memory and altered behaviour. Here determined the effect of age in SAMP8, compared with the resistant strain, SAMR1, in behaviour and learning parameters linking these disturbances with oxidative stress environment. We found impairment in emotional behaviour with regard to fear and anxiety in young SAMP8 vs. age-mated SAMR1. Differences were attenuated with age. In contrast, learning capabilities are worse in SAMP8, both in young and aged animals, with regard to SAMR1. These waves in behaviour and cognition were correlated with an excess of Oxidative stress (OS) in SAMP8 at younger ages that diminished with age. In this manner, we found changes in the hippocampal expression of ALDH2, IL-6, HMOX1, COX2, CXCL10, iNOS, and MCP-1 with an altered amyloidogenic pathway by increasing the Amyloid beta precursor protein (APP) and BACE1, and reduced ADAM10 expression; in addition, astrogliosis and neuronal markers decreased. Moreover, Superoxide dismutase 1 (SOD1) and Nuclear factor-kappa beta (NF-kβ) expression and protein levels were higher in younger SAMP8 than in SAMR1. In conclusion, the accelerated senescence process present in SAMP8 can be linked with an initial deregulation in redox homeostasis, named neuroinflammaging, by inducing molecular changes that lead to neuroinflammation and the neurodegenerative process. These changes are reflected in the emotional and cognitive behaviour of SAMP8 that differs from that of SAMR1 and that highlighted the importance of earlier oxidative processes in the onset of neurodegeneration

El impacto del centro universitario de la costa sur en el municipio de Autlán de Navarro, Jalisco, México

Con el objetivo de estimar el impacto económico, social y cultural del Centro Universitario de la Costa Sur (CU Costa Sur) en el Municipio de Autlán de la Navarro, Jalisco, México se realizó la presente tesis. Se fundamenta en la premisa de que el CU Costa Sur como una dependencia de la Universidad de Guadalajara maneja recursos económicos, empleo, incide en el desarrollo y crecimiento de empresas, en la formación de recursos humanos y el mejoramiento de las artes, la danza, el teatro y la cultura en general. Así se convierte en un foco importante de atracción que dinamiza el desarrollo social, económico y cultural en el municipio. Se utilizaron métodos y técnicas cualitativas y cuantitativas propias de la investigación educativa (McMillan y Schumacher, 2005, pp. 39-48 y 48-53). El impacto económico es aproximadamente de 176, 029,008.00 dolares para el año 2008 y para el 2015 es de 218'028,908.35 dolares, lo que representa un incremento de 23.86 porciento. El CU Costa Sur, el Ayuntamiento de Autlán de Navarro y el Ingenio Melchor Ocampo, son las organizaciones que más derrama económica tienen en el Municipio. En lo social, específicamente en la formación de recursos humanos y el desarrollo del proyecto de vida de los egresados entrevistados, se encontró que el 75% de ellos mencionó que el principal acontecimiento de su vida está relacionado con su formación en el CU Costa Sur. Se observa que cambió el horizonte de vida de los egresados que viven en el municipio. Respecto al impacto en arte y cultura en los 20 años que tiene el CU Costa Sur en la región, son miles los autlenses que se han beneficiado de la programación cultural a través de; la Semana Cultural Universitaria, que en el 2014 va en su XX edición, consolidada a nivel regional y es uno de los eventos culturales más importantes en el Estado de Jalisco; la Feria Infantil Confeti y los Cursos de Verano para niños, han fortalecido la cultura de la niñez autlense; el Premio de Pintura José Atanasio Monroy, que en el 2014 celebro su segunda bienal, está consolidado a nivel del Centro Occidente de la República Mexicana, se realiza a nivel nacional y ya es un evento esperado por los principiantes y avanzados de las artes plásticas; las Semanas de la Muerte en su XIX y la de la Navidad en su XX edición, son eventos propios de los universitarios y de la población de Autlán; la Muestra de Cine Mexicano, que recientemente, del 16 al 22 de marzo de 2015, se efectuó su edición; el apoyo del personal académico del centro universitario en las estructuras y los eventos culturales que organiza el Ayuntamiento de Autlán de Navarro, como son la Jefatura de Arte, Cultura y Turismo, en el Patronato de las Fiestas Patrias del Municipio de Autlán de Navarro y en el Patronato del Carnaval Autlán; y finalmente, en la revaloración de personajes autlenses distinguidos como son; José Atanasio Monroy, Antonio Alatorre, Rubén Villaseñor Bordes, Hermilio Hernández, Ernesto Medina Lima y Lavinia Cueva, entre otros. La opinión de los entrevistados; 12 en forma colectiva y cuatro individual, coincide al 100% en su declaración categórica de que la programación cultural del CU Costa Sur si ha impactado al Municipio de Autlán de Navarro y ha influenciado a la programación cultural del Gobierno Municipal. Se concluye que el CU Costa Sur tiene un impacto económico, social y cultural significativo en el Municipio de Autlán de Navarro y lo convierten en un importante foco de atracción que impulsa el desarrollo regional.In order to estimate the economic, social and cultural impact of the University Centre of the South Coast (Cu Costa Sur) in the city of Autlán de Navarro, Jalisco, Mexico, this thesis was conducted. It is based on the premise that the CU Costa Sur as a dependency of the University of Guadalajara manages economic resources, employment, influences the development and growth of enterprises in the training of human resources and the improvement of the arts, dance, theatre and culture in general. As a result it becomes an important centre of attraction which stimulates the social, economic and cultural development in the municipality. Qualitative and quantitative methods and techniques typical of educational research (McMillan and Schumacher, 2005, pp. 39-48 and 48-53) were used. The economic impact is approximately 176, 029,008.00 dollars for 2008 and 2015 is 218'028,908.35 dollars, representing an increase of 23.86 percent. The CU Costa Sur, the municipality of Autlán de Navarro and the sugar mill Melchor Ocampo, are organizations that have more economic benefit in the municipality. Social, specifically in human resource training and development project of life of those graduates that were interviewed, it was found that 75% of them mentioned that the main event of their life is related to their training at the CU Costa Sur. It is noted that the horizon of life of graduates living in the municipality has changed. Regarding the impact on art and culture in the 20 years that the CU Costa Sur has in the region, thousands of autlenses have been benefited from the cultural program through; University Cultural Week, which in 2014 was in the twentieth issue, consolidated at regional level it is one of the most important cultural events in the State of Jalisco; Confetti Kids Fair and Summer Courses for children, have strengthened the autlense childhood culture; Painting Prize José Atanasio Monroy, which in 2014 celebrated its second biennial, it is consolidated at West Central Mexico level, it is carried out at a national level and is an expected event by both beginners and advanced visual arts ones; the Death Week in its nineteenth issue and Christmas Week in its twentieth issue, are unique events of the university and the city of Autlan; the Mexican Film Festival, which recently edition was done, 16th to 22nd March , 2015; the support of the academic staff of the university centre in the structures and the cultural events organized by the municipality of Autlan de Navarro; such as the Art Headquarters , Culture and Tourism, in the Board of the National Holiday of the Municipality of Autlán de Navarro and the Board of Carnival Autlán; and finally, in assessing outstanding personalities autlenses such as; José Atanasio Monroy, Antonio Alatorre, Ruben Villasenor Bordes, Hermilio Hernández, Ernesto Medina Lima and Lavinia Cueva, among others. The opinion of the interviewees; 12 of them were interviewed collectively and four more individually, 100% match on their categorical statement that the cultural program of the CU Costa Sur has impacted the Municipality of Autlán de Navarro and has influenced the cultural program of the Municipal Government. It is concluded that the CU Costa Sur has a significant economic, social and cultural impact on the Municipality of Autlán de Navarro and makes it a major focus of attraction that promotes regional development

On the mechanism of phenolic formylation mediated by TiCl4 complexes: existence of diradical intermediates induced by valence tautomerism

The conventional electrophilic intramolecular aromatic substitution pathway proposed by Cresp et al. [J. Chem. Soc., Perkin Trans. 1 1973, 340 345] is confirmed by the observed products of phenolic formylation mediated by TiCl4. However, when the nucleophilic path is quenched by appropriate ligand modification, the initial equilibria between the possible neutral complexes of TiCl4 with 3,5-dimethoxy-phenol and/or diethyl ether lead to different stable diradical intermediates induced by valence tautomerism that provide valuable activated reagents. Some of these species have been detected by EPR, characterized theoretically and captured by TEMPO, thus providing a consistent mechanism for the reaction with one or more equivalents of TEMPO per phenol