Presenilin Controls CBP Levels in the Adult Drosophila Central Nervous System

Background: Dominant mutations in both human Presenilin (Psn) genes have been correlated with the formation of amyloid plaques and development of familial early-onset Alzheimer’s disease (AD). However, a definitive mechanism whereby plaque formation causes the pathology of familial and sporadic forms of AD has remained elusive. Recent discoveries of several substrates for Psn protease activity have sparked alternative hypotheses for the pathophysiology underlying AD. CBP (CREB-binding protein) is a haplo-insufficient transcriptional co-activator with histone acetly-transferase (HAT) activity that has been proposed to be a downstream target of Psn signaling. Individuals with altered CBP have cognitive deficits that have been linked to several neurological disorders. Methodology/Principal Findings: Using a transgenic RNA-interference strategy to selectively silence CBP, Psn, and Notch in adult Drosophila, we provide evidence for the first time that Psn is required for normal CBP levels and for maintaining specific global acetylations at lysine 8 of histone 4 (H4K8ac) in the central nervous system (CNS). In addition, flies conditionally compromised for the adult-expression of CBP display an altered geotaxis behavior that may reflect a neurological defect. Conclusions/Significance: Our data support a model in which Psn regulates CBP levels in the adult fly brain in a manner that is independent of Notch signaling. Although we do not understand the molecular mechanism underlying th

Isolation and characterization of canine perivascular stem/stromal cells for bone tissue engineering

For over 15 years, human subcutaneous adipose tissue has been recognized as a rich source of tissue resident mesenchymal stem/stromal cells (MSC). The isolation of perivascular progenitor cells from human adipose tissue by a cell sorting strategy was first published in 2008. Since this time, the interest in using pericytes and related perivascular stem/stromal cell (PSC) populations for tissue engineering has significantly increased. Here, we describe a set of experiments identifying, isolating and characterizing PSC from canine tissue (N = 12 canine adipose tissue samples). Results showed that the same antibodies used for human PSC identification and isolation are cross-reactive with canine tissue (CD45, CD146, CD34). Like their human correlate, canine PSC demonstrate characteristics of MSC including cell surface marker expression, colony forming unit-fibroblast (CFU-F) inclusion, and osteogenic differentiation potential. As well, canine PSC respond to osteoinductive signals in a similar fashion as do human PSC, such as the secreted differentiation factor NEL-Like Molecule-1 (NELL-1). Nevertheless, important differences exist between human and canine PSC, including differences in baseline osteogenic potential. In summary, canine PSC represent a multipotent mesenchymogenic cell source for future translational efforts in tissue engineering

Collagen Cross-linkers On Dentin Bonding: Stability Of The Adhesive Interfaces, Degree Of Conversion Of The Adhesive, Cytotoxicity And In Situ Mmp Inhibition

Objective. To investigate the effect of collagen cross-links on the stability of adhesive properties, the degree of conversion within the hybrid layer, cytotoxicity and the inhibition potential of the MMPs' activity. Methods. The dentin surfaces of human molars were acid-etched and treated with primers containing: 6.5 wt% proanthocyanidin, UVA-activated 0.1 wt% riboflavin, 5 wt% glutaraldehyde and distilled water for 60s. Following, dentin was bonded with Adper Single Bond Plus and Tetric N-Bond; and restored with resin composite. The samples were sectioned into resin-dentin "sticks" and tested for microtensile bond strength (mu TBS) after immediate (IM) and 18-month (18 M) periods. Bonded sticks at each period were used to evaluate nanoleakage and the degree of conversion (DC) under micro-Raman spectroscopy. The enzimatic activity (P1L10 cross-linkers, P1L22 MMPs' activities) in the hybrid layer was evaluated under confocal microscopy. The culture cell (NIH 3T3 fibroblast cell line) and MTT assay were performed to transdentinal cytotoxicity evaluation. Data from all tests were submitted to appropriate statistical analysis (alpha = 0.05). Results. All cross-linking primers reduced the degradation of mu TBS compared with the control group after 18 M (p > 0.05). The DC was not affected (p > 0.213). The NL increased after 18 M for all experimental groups, except for proanthocyanidin with Single Bond Plus (p > 0.05). All of the cross-link agents reduced the MMPs' activity, although this inhibition was more pronounced by PA. The cytotoxicity assay revealed reduced cell viability only for glutaraldehyde (p < 0.001). Significance. Cross-linking primers used in clinically relevant minimized the time degradation of the mu TBS without jeopardizing the adhesive polymerization, as well as reduced the collagenolytic activity of MMPs. Glutaraldeyde reduced cell viability significantly and should be avoided for clinical use. (C) 2016 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.3273274

“O Sistema Único de Saúde que dá certo”: ações de humanização no pré-natal

Objetivo: Entender como ocorre a aproximação dos pressupostos de humanização das políticas públicas e dos programas de saúde propostos pelo Ministério da Saúde na práxis da atenção pré-natal de risco habitual.Método: Estudo de campo, descritivo exploratório de abordagem qualitativa. A pesquisa foi realizada de fevereiro a junho de 2014, com observação participante e entrevista semiestruturada, em quatro unidades de saúde da família, tendo a participação de cinco enfermeiros e três médicos. Quanto à análise de dados, optou-se pela Proposta Operativa.Resultados: As categorias reveladas neste estudo que promoveram a humanização da atenção pré-natal foram: a aproximação e a vinculação da gestante e de sua família com as unidades de saúde da família e a educação permanente como facilitadora da humanização no pré-natal.Conclusões: Compreende-se que para a aproximação de uma atenção humanizada é necessário um olhar ampliado frente às singularidades das mulheres.Palavras-chave: Cuidado pré-natal. Humanização da assistência. Atenção primária à saúde. Objetivos de Desenvolvimento do Milênio

Chemical mechanism development : laboratory studies and model application

Within the German Tropospheric Research Programme (TFS) numerous kinetic and mechanistic studies on the tropospheric reaction/degradation of the following reactants were carried out:oxygenated VOC,aromatic VOC,biogenic VOC,short-lived intermediates, such as alkoxy and alkylperoxy radicals.At the conception of the projects these selected groups were classes of VOC or intermediates for which the atmospheric oxidation mechanisms were either poorly characterised or totally unknown. The motivation for these studies was the attainment of significant improvements in our understanding of the atmospheric chemical oxidation processes of these compounds, particularly with respect to their involvement in photooxidant formation in the troposphere.In the present paper the types of experimental investigations performed and the results obtained within the various projects are briefly summarised. The major achievements are highlighted and discussed in terms of their contribution to improving our understanding of the chemical processes controlling photosmog formation in the troposphere

A proposed framework for the systematic review and integrated assessment (SYRINA) of endocrine disrupting chemicals

Abstract Background: The issue of endocrine disrupting chemicals (EDCs) is receiving wide attention from both the scientific and regulatory communities. Recent analyses of the EDC literature have been criticized for failing to use transparent C exposures to adverse health or environmental outcomes. Systematic review methodologies are ideal for addressing this issue as they provide transparent and consistent approaches to study selection and evaluation. Objective methods are needed for integrating the multiple streams of evidence (epidemiology, wildlife, laboratory animal, in vitro, and in silico data) that are relevant in assessing EDCs. Methods: We have developed a framework for the systematic review and integrated assessment (SYRINA) of EDC studies. The framework was designed for use with the International Program on Chemical Safety (IPCS) and World Health Organization (WHO) definition of an EDC, which requires appraisal of evidence regarding 1) association between exposure and an adverse effect, 2) association between exposure and endocrine disrupting activity, and 3) a plausible link between the adverse effect and the endocrine disrupting activity. Results: Building from existing methodologies for evaluating and synthesizing evidence, the SYRINA framework includes seven steps: 1) Formulate the problem; 2) Develop the review protocol; 3) Identify relevant evidence; 4) Evaluate evidence from individual studies; 5) Summarize and evaluate each stream of evidence; 6) Integrate evidence across all streams; 7) Draw conclusions, make recommendations, and evaluate uncertainties. The proposed method is tailored to the IPCS/WHO definition of an EDC but offers flexibility for use in the context of other definitions of EDCs. Conclusions: When using the SYRINA framework, the overall objective is to provide the evidence base needed to support decision making, including any action to avoid/minimise potential adverse effects of exposures. This framework allows for the evaluation and synthesis of evidence from multiple evidence streams. Finally, a decision regarding regulatory action is not only dependent on the strength of evidence, but also the consequences of action/inaction, e.g. limited or weak evidence may be sufficient to justify action if consequences are serious or irreversible