Analysis of SNAP25 mRNA expression and promoter DNA methylation in brain areas of Alzheimer’s Disease patients

Alzheimer's Disease (AD) is the most common cause of dementia in elderly people. the presynaptic terminal is an important site of pathological changes in AD, leading to synaptic loss in specific brain regions, such as in the cortex and hippocampus. in this study, we investigated synaptosomal-associated protein, 25-kDa (SNAP25) mRNA levels and promoter DNA methylation in post mortem brain tissues (entorhinal and auditory cortices and hippocampus) from healthy elderly and AD subjects as well as in peripheral blood leukocytes of young, healthy elderly and AD patients. mRNA quantification was performed by quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) using the Delta Delta C-T method and promoter DNA methylation was quantified by mass spectrometry using the Sequenom EpiTYPER platform. We observed a significant decrease in SNAP25 expression in AD across all the three brain regions in relation to the healthy elderly subjects, suggesting impairment in synaptic function. the changes in the auditory cortex reflected those observed in the hippocampus and entorhinal cortex, the primary areas affected in AD. However, no AD-associated differences in SNAP25 promoter DNA methylation were observed suggesting that other mechanisms may be involved in mediating the observed gene expression changes. (C) 2012 IBRO. Published by Elsevier B.V. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Disciplina Genet, Dept Morfol & Genet, São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Neurol Clin, Dept Neurol Neurocirurgia, São Paulo, BrazilFac Med Marilia FAMEMA, Hemoctr, Genet Lab, Marilia, SP, BrazilMcGill Univ, Dept Psychiat, Douglas Hosp Res Ctr, Montreal, PQ, CanadaKings Coll London, Inst Psychiat, London WC2R 2LS, EnglandUniv Sagrado Coracao, Bauru, SP, BrazilUniversidade Federal de São Paulo, Disciplina Genet, Dept Morfol & Genet, São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Neurol Clin, Dept Neurol Neurocirurgia, São Paulo, BrazilWeb of Scienc

A Declarative Approach to View Selection Modeling

Abstract. View selection is important in many data-intensive systems e.g., commercial database and data warehousing systems. Given a database (or a data warehouse) schema and a query workload, view selection is to choose an appropriate set of views to be materialized that optimizes the total query cost, given a limited amount of resource, e.g., storage space and total view maintenance cost. The view selection problem is known to be a NP-complete problem. In this paper, we propose a declarative approach that involves a constraint programming technique which is known to be e cient for the resolution of NP-complete problems. The originality of our approach is that it provides a clear separation between formulation and resolution of the problem. For this purpose, the view selection problem is modeled as a constraint satisfaction problem in an easy and declarative way. Then, its resolution is performed automatically by the constraint solver. Furthermore, our approach is exible and extensible, in that it can easily model and handle new constraints and new heuristic search strategies to reduce the solution space. The performance results show that our approach outperforms the genetic algorithm which is known to provide the best trade-o between quality of solutions in terms of cost saving and execution time

'To Create Her World Anew': Charlotte Salomon's Graphic Life Narrative

This chapter discusses Charlotte Salomon’s Life? or Theatre?, a sequence of 784 paintings created between 1940 and 1942 by a young German-Jewish artist. Focusing upon three key paintings within the cycle, and in particular their representations of open windows, this chapter argues that Life? or Theatre? is a complex, kaleidoscopic rendering of multiple graphic life stories, which can be opened up and better understood through the vocabulary of comics criticism. By focusing on the spaces between pages—the gutter—this chapter exposes how these are vital, generative gaps charged with meaning. In so doing it challenges reductive, biographical readings of Salomon’s life and work, insisting that Life? or Theatre? is a visual and textual representation of many life narratives, taking on the shapeshifting form of an epic, reiterative cycle