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Renal neoplasia is the 14th most common tumor type diagnosed worldwide. With a vast heterogeneity, renal neoplasia encompasses different subtypes. 90% of the neoplasms arise from the epithelial layer of the nephron and vary from benign renal masses (renal oncocytoma, RO) to more indolent or aggressive cancers (renal cell carcinomas, RCC). As RCC subtypes, clear cell (ccRCC) subtype is the most predominant subtype, followed by papillary (pRCC) and chromophobe (chRCC). Despite the different outcomes, some overlapped histological and morphological features difficult their differentiation and diagnosis. Therefore, new approaches for a clear and accurate diagnosis are still needed. To achieve this goal, renal tissue biopsies diagnosed with ccRCC (n = 7), pRCC (n = 5), chRCC (n = 5), RO (n = 5) and normal adjacent tissue (NAT, n= 5) were enrolled in this study. As a very resourceful tool for proteome analysis and biomarker discovery, mass spectrometry (MS)-based methods were used to interrogate the proteome of each tumor in order to undisclosed differences trough which to develop faster and accurate diagnostics. The results achieved with this doctoral thesis include i) the accomplishment of an effective ultrasonic workflow to recover the proteome of optimal cutting temperature (OCT)-embedded tissues, ii) a novel analytical approach based on MALDI-MS profiling to distinguish chRCC from RO, iii) a 109-protein panel to discriminate between chRCC and RO and NAT, iv) a top 24-protein panel to diagnose ccRCC, pRCC, chRCC and RO based on absolute concentration values, v) the translation and validation of three promising biomarkers by immunohistochemical analysis, and vi) an approach for phosphopeptide enrichment. This work brings new insights into the different mechanisms underlying formation of these tumors as well as it provides valuable information to improve clinical diagnosis by opening new avenues for immunohistochemistry and mass spectrometry-based approaches.

A pesca é uma das profissões mais perigosas. No entanto, poucos têm sido os estudos desenvolvidos quanto à Segurança e Saúde no Trabalho no grupo de trabalhadores desta indústria. A presente investigação foi realizada numa amostra de 14 pescadores ao serviço de uma embarcação de pesca por arte de cerco (traineira) que opera na região do Algarve, obtida por conveniência. O estudo teve como objetivo determinar os níveis de pressão sonora nos locais de trabalho e a exposição pessoal diária de cada trabalhador, avaliar a capacidade auditiva de cada trabalhador e nomeadamente se existem traços sugestivos de surdez sonotraumática, bem como avaliar a perceção de risco individual associada ao ruído neste grupo de trabalhadores. Para alcançar os objetivos definidos foram necessárias três fases de recolha de dados com recurso a diferentes instrumentos. Inicialmente efetuaram-se medições de ruído nos diferentes locais de trabalho da traineira. Posteriormente, os pescadores foram submetidos a exames audiométricos constituídos por otoscopia, timpanometria e audiometria tonal. Por último, a amostra respondeu a um questionário, por heteroadministração, dividido em três partes distintas: caracterização socioprofissional, anamnese audiológica ocupacional e perceção de risco associada ao ruído. Os resultados obtidos demonstraram que os pescadores alvo de estudo encontram-se expostos a elevados níveis de pressão sonora, que ultrapassam os valores de ação inferiores e os valores limites de exposição definidos na legislação. Metade dos trabalhadores apresentaram perda auditiva, sendo que quatro destes tinham traços sugestivos da perda ser induzida pelo ruído. Verificou-se que a perceção de risco individual é baixa, havendo trabalhadores com fracos conhecimentos acerca das fontes de ruído ou dos efeitos causados pela exposição prolongada. Marine fishing is one of the most dangerous occupations. However, few studies have been conducted regarding Health and Safety at Work in this industry workers. The present investigation was carried out on a sample of 14 fishermen on the service of a seiner fishing vessel (trawler) operating in the Algarve region, obtained for convenience. The study aimed to determine the sound pressure levels in the workplaces and the daily personal exposure of each worker, assessing the individual hearing capacity and, in particular, whether there are traits suggestive of noise induced hearing loss, as well as assessing the individual risk perception associated with noise in this group of workers. To achieve the defined objectives, three steps of data collection were necessary, using different instruments. Initially, sound pressure levels were measured in different vessel compartments. Afterwards, audiometric examinations consisting of otoscopy, tympanometry and pure tone audiometry were performed on the fishermen. Finally, the sample answered a questionnaire, by heteroadministration, divided into three distinct parts: socio-demographic profile, occupational audiological anamnesis and risk perception associated with noise. The results obtained showed that the fisehermen are exposed to high sound pressure levels, which exceed the lower action values and the exposure limit values recommended by the Portuguese legislation. Half of the workers had hearing loss, and four of them had traits suggesting noise induced hearing loss. It was found that the individual risk perception is low, with workers having poor knowledge about the sources of noise or the effects caused by continued exposure.

Dissertação de Mestrado , apresentada no ISPA – Instituto Universitário para obtenção de grau de Mestre na especialidade de Psicologia da Saúde Submitted by Paulo Pinhão Nunes (pnunes@ispa.pt) on 2019-09-11T10:47:58Z No. of bitstreams: 22 23218-Consistência Interna Social.pdf: 11034 bytes, checksum: d957551ad6bae2e0e1e385e24ba15c18 (MD5) 23218-Diablumia Output's.pdf: 210533 bytes, checksum: 8faf1f02c2d0ab3237a41f943b08059c (MD5) 23218-diabulimiatese output.spv: 147649 bytes, checksum: e8c68240ef12c19ea899321276563f52 (MD5) 23218-diabumiliatese.sav: 50038 bytes, checksum: b9d33266ff9eea3bf4ec5d7376c0bfa7 (MD5) 23218-MODELO 1.amw: 98792 bytes, checksum: 3c4217a127f7312e2d8a121390f1547e (MD5) 23218-MODELO 2.amw: 106628 bytes, checksum: 3ab250aeac8af4f2c7d5ef6cac5aeac3 (MD5) 23218-Motivações para a Atividade Física.pdf: 261237 bytes, checksum: 5f8feed7dc468092ad8abc08b657ab25 (MD5) 23218.pdf: 2137541 bytes, checksum: 0bbbe0e545e9fbeaa9c1ce7c61895ef4 (MD5) 23218-Análise Confirmatória Adesão ao Tratamento.pdf: 65887 bytes, checksum: 1ebb012a12563b79b9c8594c3b71cfb3 (MD5) 23218 - Cópia.pdf: 2137541 bytes, checksum: 0bbbe0e545e9fbeaa9c1ce7c61895ef4 (MD5) 23218-Análise Confirmatória Comportamento Alimentar.pdf: 149082 bytes, checksum: ce42a971fba0ac49a6e011b4d3c8731e (MD5) 23218-Análise Confirmatória Imagem Corporal.pdf: 94467 bytes, checksum: fbe5d94d8fdee5f5ba8ada2f31a4abe2 (MD5) 23218-Análise da Sensibilidade da Adesão ao tratamento.pdf: 105365 bytes, checksum: c96553690b8664b74dd7087433bc77f1 (MD5) 23218-Análise da Sensibilidade do Comportamento Alimentar.pdf: 119262 bytes, checksum: be2a4d0a790c0db2f7aaaed411ec07d5 (MD5) 23218-Análise da Sensibilidade MAF 28.pdf: 121750 bytes, checksum: a5378c7bec90ed8903f0e452ad5396e5 (MD5) 23218-Análise da Sensibilidade Imagem Corporal.pdf: 13943 bytes, checksum: 94dde61a94212f7ad2bf475f46d00f76 (MD5) 23218-Consistência Interna Adesão Terapêutica.pdf: 13786 bytes, checksum: c55745d70dcf558b8357be64af51bd45 (MD5) 23218-Consistência Interna Aparência.pdf: 12858 bytes, checksum: 146557d996663c5c5018bca531ffebc4 (MD5) 23218-Consistência Interna Competência.pdf: 13103 bytes, checksum: 4e8a4e828e0270c54c11b95052204820 (MD5) 23218-Consistência Interna Descontrolo Alimentar.pdf: 15571 bytes, checksum: fe7e4e9b92eadf2d5d8107b947c7d5b6 (MD5) 23218-Consistencia Interna Diversão.pdf: 13637 bytes, checksum: 6e4d5538fa58e03b29faf9a6adb47e9a (MD5) 23218-Consistência Interna Saúde.pdf: 12126 bytes, checksum: 115c1fdb956cd6b4a9310549f871d126 (MD5) Made available in DSpace on 2019-09-11T10:47:58Z (GMT). No. of bitstreams: 22 23218-Consistência Interna Social.pdf: 11034 bytes, checksum: d957551ad6bae2e0e1e385e24ba15c18 (MD5) 23218-Diablumia Output's.pdf: 210533 bytes, checksum: 8faf1f02c2d0ab3237a41f943b08059c (MD5) 23218-diabulimiatese output.spv: 147649 bytes, checksum: e8c68240ef12c19ea899321276563f52 (MD5) 23218-diabumiliatese.sav: 50038 bytes, checksum: b9d33266ff9eea3bf4ec5d7376c0bfa7 (MD5) 23218-MODELO 1.amw: 98792 bytes, checksum: 3c4217a127f7312e2d8a121390f1547e (MD5) 23218-MODELO 2.amw: 106628 bytes, checksum: 3ab250aeac8af4f2c7d5ef6cac5aeac3 (MD5) 23218-Motivações para a Atividade Física.pdf: 261237 bytes, checksum: 5f8feed7dc468092ad8abc08b657ab25 (MD5) 23218.pdf: 2137541 bytes, checksum: 0bbbe0e545e9fbeaa9c1ce7c61895ef4 (MD5) 23218-Análise Confirmatória Adesão ao Tratamento.pdf: 65887 bytes, checksum: 1ebb012a12563b79b9c8594c3b71cfb3 (MD5) 23218 - Cópia.pdf: 2137541 bytes, checksum: 0bbbe0e545e9fbeaa9c1ce7c61895ef4 (MD5) 23218-Análise Confirmatória Comportamento Alimentar.pdf: 149082 bytes, checksum: ce42a971fba0ac49a6e011b4d3c8731e (MD5) 23218-Análise Confirmatória Imagem Corporal.pdf: 94467 bytes, checksum: fbe5d94d8fdee5f5ba8ada2f31a4abe2 (MD5) 23218-Análise da Sensibilidade da Adesão ao tratamento.pdf: 105365 bytes, checksum: c96553690b8664b74dd7087433bc77f1 (MD5) 23218-Análise da Sensibilidade do Comportamento Alimentar.pdf: 119262 bytes, checksum: be2a4d0a790c0db2f7aaaed411ec07d5 (MD5) 23218-Análise da Sensibilidade MAF 28.pdf: 121750 bytes, checksum: a5378c7bec90ed8903f0e452ad5396e5 (MD5) 23218-Análise da Sensibilidade Imagem Corporal.pdf: 13943 bytes, checksum: 94dde61a94212f7ad2bf475f46d00f76 (MD5) 23218-Consistência Interna Adesão Terapêutica.pdf: 13786 bytes, checksum: c55745d70dcf558b8357be64af51bd45 (MD5) 23218-Consistência Interna Aparência.pdf: 12858 bytes, checksum: 146557d996663c5c5018bca531ffebc4 (MD5) 23218-Consistência Interna Competência.pdf: 13103 bytes, checksum: 4e8a4e828e0270c54c11b95052204820 (MD5) 23218-Consistência Interna Descontrolo Alimentar.pdf: 15571 bytes, checksum: fe7e4e9b92eadf2d5d8107b947c7d5b6 (MD5) 23218-Consistencia Interna Diversão.pdf: 13637 bytes, checksum: 6e4d5538fa58e03b29faf9a6adb47e9a (MD5) 23218-Consistência Interna Saúde.pdf: 12126 bytes, checksum: 115c1fdb956cd6b4a9310549f871d126 (MD5) Previous issue date: 2019-07-17

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Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are known as the most frequent cause of familial Parkinson's disease (PD), but are also present in sporadic cases. The G2019S-LRRK2 mutation is located in the kinase domain of the protein, and has consistently been reported to promote a gain of kinase function. Several proteins have been reported as LRRK2 substrates and/or interactors, suggesting possible pathways involved in neurodegeneration in PD. Hyperphosphorylated Tau protein accumulates in neurofibrillary tangles, a typical pathological hallmark in Alzheimer's disease and frontotemporal dementia. In addition, it is also frequently found in the brains of PD patients. Although LRRK2 is a kinase, it appears that a putative interaction with Tau is phosphorylation-independent. However, the underlying mechanisms and the cellular consequences of this interaction are still unclear. In this study, we demonstrate an interaction between LRRK2 and Tau and that LRRK2 promotes the accumulation of non-monomeric and high-molecular weight (HMW) Tau species independent of its kinase activity. Interestingly, we found that LRRK2 increases Tau secretion, possibly as a consequence of an impairment of Tau proteasomal degradation. Our data highlight a mechanism through which LRRK2 regulates intracellular Tau levels, contributing to the progression of the pathology caused by the LRRK2-mediated proteasome impairment. In total, our findings suggest that the interplay between LRRK2 and proteasome activity might constitute a valid target for therapeutic intervention in PD.

Alpha-synuclein (aSyn) misfolding and aggregation are pathological features common to several neurodegenerative diseases, including Parkinson's disease (PD). Mounting evidence suggests that aSyn can be secreted and transferred from cell to cell, participating in the propagation and spreading of pathological events. Rab11, a small GTPase, is an important regulator in both endocytic and secretory pathways. Here, we show that Rab11 is involved in regulating aSyn secretion. Rab11 knockdown or overexpression of either Rab11a wild-type (Rab11a WT) or Rab11a GDP-bound mutant (Rab11a S25N) increased secretion of aSyn. Furthermore, we demonstrate that Rab11 interacts with aSyn and is present in intracellular inclusions together with aSyn. Moreover, Rab11 reduces aSyn aggregation and toxicity. Our results suggest that Rab11 is involved in modulating the processes of aSyn secretion and aggregation, both of which are important mechanisms in the progression of aSyn pathology in PD and other synucleinopathies.

© Springer Science+Business Media New York 2016, The protein α-synuclein (α-Syn) interferes with glucose and lipid uptake and also activates innate immune cells. However, it remains unclear whether α-Syn or its familial mutant forms contribute to metabolic alterations and inflammation in synucleinopathies, such as Parkinson's disease (PD). Here, we address this issue in transgenic mice for the mutant A53T human α-Syn (α-SynA53T), a mouse model of synucleinopathies. At 9.5 months of age, mice overexpressing α-SynA53T (homozygous) had a significant reduction in weight, exhibited improved locomotion and did not show major motor deficits compared with control transgenic mice (heterozygous). At 17 months of age, α-SynA53T overexpression promoted general reduction in grip strength and deficient hindlimb reflex and resulted in severe disease and mortality in 50 % of the mice. Analysis of serum metabolites further revealed decreased levels of cholesterol, triglycerides and non-esterified fatty acids (NEFA) in α-SynA53T-overexpressing mice. In fed conditions, these mice also showed a significant decrease in serum insulin without alterations in blood glucose. In addition, assessment of inflammatory gene expression in the brain showed a significant increase in TNF-α mRNA but not of IL-1β induced by α-SynA53T overexpression. Interestingly, the brain mRNA levels of Sirtuin 2 (Sirt2), a deacetylase involved in both metabolic and inflammatory pathways, were significantly reduced. Our findings highlight the relevance of the mechanisms underlying initial weight loss and hyperactivity as early markers of synucleinopathies. Moreover, we found that changes in blood metabolites and decreased brain Sirt2 gene expression are associated with motor deficits., This work was funded by Fundação para a Ciência e Tecnologia, Portugal (PTDC/SAU-ORG/114083/2009). TFP was “Investigador FCT”; JEC is a postdoctoral FCT fellow (BPD/87647/2012); LVL is an “Investigador FCT”; TFO is supported by the DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB).

In order to achieve excellence, an organization should use two key instruments—quality and an effi cient and effective communication process amongst all employees—so it can attain quality management. This chapter aims to examine whether organizational communication and quality are interrelated, in order to answer the following question: Is it necessary to improve communication within an organization so that quality management can be effi ciently and effectively pursued? For this purpose, data were collected through the administration of a questionnaire to the staff of a Portuguese public organization. The fi ndings showed that, in this organization, communication among employees of various sectors is satisfactory and that there is mutual help between them in order to improve the organizational performance.

Mestrado em Contabilidade, Fiscalidade e Finanças Empresariais Este relatório procura reproduzir, de forma sucinta, todo o trabalho desenvolvido e realizado enquanto assistente de auditoria, na empresa Victor José & Associados, durante um período de 4 meses (400 horas). Complementarmente realizou-se um estudo, nos clientes da entidade acolhedora, sobre o impacto da Proposta de Lei n.o334/XII (2015) na continuidade dos serviços de auditoria. Dos 33 clientes que colaboraram, 63,63% indicaram que iriam continuar a sujeitar-se/contratar serviços de auditoria de forma voluntária. Como principais benefícios dos serviços de auditoria, 38,10% apontaram que aumentariam a credibilidade das demonstrações financeiras e 33,33% indicaram que melhorariam a qualidade da informação financeira. Constatou-se que quanto maior é a entidade, maior é a probabilidade de se sujeitarem/contratarem serviços de auditoria, de forma voluntária. Mas não se verificou associação positiva entre o nível de satisfação dos serviços atualmente recebidos com a decisão das entidades de se sujeitarem/contratarem serviços de auditoria, de forma voluntária. The following report results from an effort to sum up the development and the application stages of the proposed project as an audit assistant in the company Victor José &Associados for a period of 4 months, in a total of 400 hours. At the same time, a study was organized as a mean to evaluate the impact of the law proposal n.o334/XII (2015) regarding the voluntarily continuity of auditing services. Of the 33 clients who willingly participated, 63, 63% answered they would voluntarily continuing hiring auditing services. 38, 10% pointed the demonstrations of financial credibility as one of the main beneficial features of the auditing services hired, while 33, 33% pointed the improvement of financial information quality. From the results it was possible to conclude that as companies get larger, the higher the probability gets, that these companies will voluntarily hire auditing services. Yet, it was not possible to find a positive association between the levels of satisfaction with actual hired services and the decision of companies to voluntarily hire auditing services.

Copyright: © 2014 Lázaro et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited., Aggregation of alpha-synuclein (ASYN) in Lewy bodies and Lewy neurites is the typical pathological hallmark of Parkinson's disease (PD) and other synucleinopathies. Furthermore, mutations in the gene encoding for ASYN are associated with familial and sporadic forms of PD, suggesting this protein plays a central role in the disease. However, the precise contribution of ASYN to neuronal dysfunction and death is unclear. There is intense debate about the nature of the toxic species of ASYN and little is known about the molecular determinants of oligomerization and aggregation of ASYN in the cell. In order to clarify the effects of different mutations on the propensity of ASYN to oligomerize and aggregate, we assembled a panel of 19 ASYN variants and compared their behaviour. We found that familial mutants linked to PD (A30P, E46K, H50Q, G51D and A53T) exhibited identical propensities to oligomerize in living cells, but had distinct abilities to form inclusions. While the A30P mutant reduced the percentage of cells with inclusions, the E46K mutant had the opposite effect. Interestingly, artificial proline mutants designed to interfere with the helical structure of the N-terminal domain, showed increased propensity to form oligomeric species rather than inclusions. Moreover, lysine substitution mutants increased oligomerization and altered the pattern of aggregation. Altogether, our data shed light into the molecular effects of ASYN mutations in a cellular context, and established a common ground for the study of genetic and pharmacological modulators of the aggregation process, opening new perspectives for therapeutic intervention in PD and other synucleinopathies., This work was supported by the DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB).

Alpha-synuclein (αS) misfolding is associated with Parkinson's disease (PD) but little is known about the mechanisms underlying αS toxicity. Increasing evidence suggests that defects in membrane transport play an important role in neuronal dysfunction. Here we demonstrate that the GTPase Rab8a interacts with αS in rodent brain. NMR spectroscopy reveals that the C-terminus of αS binds to the functionally important switch region as well as the C-terminal tail of Rab8a. In line with a direct Rab8a/αS interaction, Rab8a enhanced αS aggregation and reduced αS-induced cellular toxicity. In addition, Rab8 – the Drosophila ortholog of Rab8a – ameliorated αS-oligomer specific locomotor impairment and neuron loss in fruit flies. In support of the pathogenic relevance of the αS–Rab8a interaction, phosphorylation of αS at S129 enhanced binding to Rab8a, increased formation of insoluble αS aggregates and reduced cellular toxicity. Our study provides novel mechanistic insights into the interplay of the GTPase Rab8a and αS cytotoxicity, and underscores the therapeutic potential of targeting this interaction. Fil: Yin, Guowei. Max Planck Institute Of Biochemistry.; Alemania Fil: Lopes da Fonseca, Tomas. Universität Göttingen; Alemania. Research Center Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania Fil: Eisbach, Sibylle E.. Universität Göttingen; Alemania. Research Center Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania Fil: Anduaga, Ane Martin. University of Leicester; Reino Unido Fil: Breda, Carlo. University of Leicester; Reino Unido Fil: Orcellet, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina Fil: Szegő, Eva M.. Universität Göttingen; Alemania. Research Center Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania Fil: Guerreiro, Patria. Universität Göttingen; Alemania. Research Center Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania Fil: Lázaro, Diana F.. Universität Göttingen; Alemania. Research Center Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania Fil: Braus, Gerhard H.. Universität Göttingen; Alemania. Research Center Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania Fil: Fernandez, Claudio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina Fil: Griesinger, Christian. Max Planck Institute for Biophysical Chemistry; Alemania Fil: Becker, Stefan. Max Planck Institute for Biophysical Chemistry; Alemania Fil: Goody, Roger S.. Max-Planck-Institute of Molecular Physiology; Alemania Fil: Itzen, Aymelt. Universitat Technical Zu Munich; Alemania. Max-Planck-Institute of Molecular Physiology; Alemania Fil: Giorgini, Flaviano. University of Leicester; Reino Unido Fil: Outeiro, Tiago F.. Universität Göttingen; Alemania. Research Center Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania Fil: Zweckstetter, Markus. Max Planck Institute for Biophysical Chemistry; Alemania. German Center for Neurodegenerative Diseases; Alemania. Research Center Nanoscale Microscopy and Molecular Physiology of the Brain; Alemania

Para se atingir a excelência numa organização esta deve utilizar dois instrumentos essenciais: a qualidade e uma comunicação eficiente e eficaz entre todos os trabalhadores, pois é através desta que se pode atingir a gestão pela qualidade. O presente trabalho tem como objetivo principal averiguar se a comunicação organizacional e a qualidade estão interligadas, isto é, qual a necessidade em melhorar a comunicação dentro de uma organização, de modo a desenvolver-se eficazmente uma gestão pela qualidade. Para tal, efetuou-se uma recolha de dados através da aplicação de questionários aos trabalhadores da Câmara Municipal de Santiago do Cacém. Quanto ao conteúdo, o instrumento de recolha de dados foi adaptado dos questionários aplicados nas investigações de Quintino (2009), do artigo científico de Downs e Hazen (1977) e do livro adaptado por Goldhaber e Rogers (1979). Os resultados obtidos revelaram que nesta organização a comunicação entre os trabalhadores dos vários setores é satisfatória e que existe entreajuda entre os mesmos, afim de melhorar o desempenho organizacional; Abstract: Quality for effective communication in organizations. Case study in the Câmara Municipal de Santiago do Cacém. In order to attain excellence in an organization, two key tools should be used: Quality and an efficient and effective Communication between all employees. Only through these tools can we achieve quality management. This study aims to determine whether or not organizational communication and quality are interrelated. That is to say, to identify the need to improve communication within an organization in order to effectively develop quality management. To this end, data was collected through questionnaires given to employees of the Câmara Municipal de Santiago do Cacém. Regarding content, the instrument of data collection was adapted from questionnaires used in investigations of Quintino (2009), the scientific article by Downs and Hazen (1977) and adapted from the book by Goldhaber and Rogers (1979). The results obtained revealed that the communication between the employees of various sectors within the organization is satisfactory and that there exists mutual assistance between the employees in order to improve the organizational performance.

Copyright © 2012 the authors, Parkinson's disease (PD) is the most common representative of a group of disorders known as synucleinopathies, in which misfolding and aggregation of α-synuclein (a-syn) in various brain regions is the major pathological hallmark. Indeed, the motor symptoms in PD are caused by a heterogeneous degeneration of brain neurons not only in substantia nigra pars compacta but also in other extrastriatal areas of the brain. In addition to the well known motor dysfunction in PD patients, cognitive deficits and memory impairment are also an important part of the disorder, probably due to disruption of synaptic transmission and plasticity in extrastriatal areas, including the hippocampus. Here, we investigated the impact of a-syn aggregation on AMPA and NMDA receptor-mediated rat hippocampal (CA3-CA1) synaptic transmission and long-term potentiation (LTP), the neurophysiological basis for learning and memory. Our data show that prolonged exposure to a-syn oligomers, but not monomers or fibrils, increases basal synaptic transmission through NMDA receptor activation, triggering enhanced contribution of calcium-permeable AMPA receptors. Slices treated with a-syn oligomers were unable to respond with further potentiation to theta-burst stimulation, leading to impaired LTP. Prior delivery of a low-frequency train reinstated the ability to express LTP, implying that exposure to a-syn oligomers drives the increase of glutamatergic synaptic transmission, preventing further potentiation by physiological stimuli. Our novel findings provide mechanistic insight on how a-syn oligomers may trigger neuronal dysfunction and toxicity in PD and other synucleinopathies., This research is supported by a Marie Curie International Reintegration Grant (Neurofold; T.F.O.), an EMBO Installation Grant, Fundação para a Ciência e Tecnologia (FCT), PTDC/QUI/73430/2006 Grant from FCT (A.Q), PDCT/SAU-NMC/099853/2008 from FCT (L.V.L.), PDCT/SAU-NMC/110838/2009 from FCT (A.M.S.), FCT fellowships SFRH/BD/60386/2009 (D.M.R.) and SFRH/BD/27761/2006 (R.B.D.), FCT fellowship SFRH/BPD/64702/2009 (H.V.M.), and by the University of Rome Sapienza (F.M.). We also thank Alex Kasrayan and Monica Ekberg for the production of recombinant a-syn.

Dissertação de mest., Biotecnologia, Faculdade de Ciências e Tecnologia, Univ. do Algarve, 2011 Perrault syndrome is a rare autosomal recessive disorder and its hallmarks are bilateral sensorineural hearing loss in both female and male, ovarian dysgenesis in females and in some patients neurological abnormalities, revealing a clinical heterogeneity. Two genes have already been associated with the syndrome in two families, however they do not explain the disease in all affected individuals. Four affected patients, three females and one male from the same large consanguineous family with unaffected parents, were diagnosed with Perrault syndrome, suggesting a default inherited by descent from a common ancestor. The aim of the study was to identify the gene that is responsible for the disease by determining the causal mutation. In a first step, using genome-wide SNP genotyping, we delineated a single large genomic segment that was homozygous in all patients, at chr19:608,234-6,766,463. This segment is hence expected to encompass the causal mutation. Then, using bioinformatic tools the genes present there were prioritized and the AMH, KISS1R, TCF3 and DAZAP1 were chosen as possible candidates for the defect. These genes were sequenced in the four patients by direct dideoxy incorporation (Sanger) in search of a pathogenic mutation. No mutation was found. As the gene harboring the genetic cause of the syndrome remained unidentified, the full exome of one proband was sequenced by massively parallel sequencing and an homozygous variant in the ZNF77 gene was identified, which was present in all affected patient of the family. However we found copies of this mutation in control subjects from the same ethnic group, with an estimated allelic frequency that would result in 1 affected individual in 300. Considering the possibility of compound heterozygosity in spite of parental consanguinity, we re-examined the full exome, but failed to identify a gene with robust evidence for bi-allelic inactivation. We conclude that the candidate gene analyses and full exome sequencing very likely failed to identify the causal gene, either because of insufficient sequencing depth, or because the mutation was non coding, or because the mutated exon was not captured by the exome sequencing approach.

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Dissertação (mestrado)-Universidade de Brasília, Instituto de Letras, Departamento de Teoria Literária e Literaturas, Brasília, 2006. Texto parcialmente liberado pelo autor. Conteúdo: Capítulos 1,2 e 3. Esta dissertação tem como tema o duplo. Procuramos situá-lo desde a sua origem, por meio de textos crítico-teóricos que o desenvolveram. Nesse sentido, escolhemos textos literários de Guy de Maupassant, Robert-Louis Stevenson, Edgar Allan Poe, Fiodor Dostoievski, Michel de Montaigne e de Jorge Luis Borges, que nos forneceram elementos cruciais a essa reflexão, pela forma como apresentaram a compreensão das personagens duplicadas, pela maneira como são construídas e como estas expressam a sua visão de mundo e de si mesmas aos leitores. _____________________________________________________________________________________ ABSTRACT This dissertation has to theme the double-ganger. Shall find situate since the your origin, by means of texts critical-theoretical that the development. Therein, we work on texts literaries from Guy de Maupassant, Robert-Louis Stevenson, Edgar Allan Poe, Fiodor Dostoievski, Michel de Montaigne and from Jorge Luis Borges, that we to frame elements crucial to this reflexion, by way how presents the comprehension the persons doubles, by way as was construct and how these express your vision to the world and to the lectors.

Mutations in the genes encoding leucine-rich repeat kinase 2 (LRRK2) and α-synuclein are associated with both autosomal dominant and idiopathic forms of Parkinson’s disease (PD). α-Synuclein is the main protein in Lewy bodies, hallmark inclusions present in both sporadic and familial PD. We show that in PD brain tissue, the levels of LRRK2 are positively related to the increase in α-synuclein phosphorylation and aggregation in affected brain regions (amygdala and anterior cingulate cortex), but not in the unaffected visual cortex. In disease-affected regions, we show co-localization of these two proteins in neurons and Lewy body inclusions. Further, in vitro experiments show a molecular interaction between α-synuclein and LRRK2 under endogenous and over-expression conditions. In a cell culture model of α-synuclein inclusion formation, LRRK2 co-localizes with the α-synuclein inclusions, and knocking down LRRK2 increases the number of smaller inclusions. In addition to providing strong evidence for an interaction between LRRK2 and α-synuclein, our results shed light on the complex relationship between these two proteins in the brains of patients with PD and the underlying molecular mechanisms of the disease. Electronic supplementary material The online version of this article (doi:10.1007/s00109-012-0984-y) contains supplementary material, which is available to authorized users.