ATP release due to Thy-1-integrin binding induces P2X7-mediated calcium entry required for focal adhesion formation.

Thy-1, an abundant mammalian glycoprotein, interacts with αvβ3 integrin and syndecan-4 in astrocytes and thus triggers signaling events that involve RhoA and its effector p160ROCK, thereby increasing astrocyte adhesion to the extracellular matrix. The signaling cascade includes calcium-dependent activation of protein kinase Cα upstream of Rho; however, what causes the intracellular calcium transients required to promote adhesion remains unclear. Purinergic P2X7 receptors are important for astrocyte function and form large non-selective cation pores upon binding to their ligand, ATP. Thus, we evaluated whether the intracellular calcium required for Thy-1-induced cell adhesion stems from influx mediated by ATP-activated P2X7 receptors. Results show that adhesion induced by the fusion protein Thy-1-Fc was preceded by both ATP release and sustained intracellular calcium elevation. Elimination of extracellular ATP with Apyrase, chelation of extracellular calcium with EGTA, or inhibition of P2X7 with oxidized ATP, all individually blocked intracellular calcium increase and Thy-1-stimulated adhesion. Moreover, Thy-1 mutated in the integrin-binding site did not trigger ATP release, and silencing of P2X7 with specific siRNA blocked Thy-1-induced adhesion. This study is the first to demonstrate a functional link between αvβ3 integrin and P2X7 receptors, and to reveal an important, hitherto unanticipated, role for P2X7 in calcium-dependent signaling required for Thy-1-stimulated astrocyte adhesion.

Neuronal Thy-1 induces astrocyte adhesion by engaging syndecan-4 in a cooperative interaction with alphavbeta3 integrin that activates PKCalpha and RhoA.

Clustering of alphavbeta3 integrin after interaction with the RGD-like integrin-binding sequence present in neuronal Thy-1 triggers formation of focal adhesions and stress fibers in astrocytes via RhoA activation. A putative heparin-binding domain is present in Thy-1, raising the possibility that this membrane protein stimulates astrocyte adhesion via engagement of an integrin and the proteoglycan syndecan-4. Indeed, heparin, heparitinase treatment and mutation of the Thy-1 heparin-binding site each inhibited Thy-1-induced RhoA activation, as well as formation of focal adhesions and stress fibers in DI TNC(1) astrocytes. These responses required both syndecan-4 binding and signaling, as evidenced by silencing syndecan-4 expression and by overexpressing a syndecan-4 mutant lacking the intracellular domain, respectively. Furthermore, lack of RhoA activation and astrocyte responses in the presence of a PKC inhibitor or a dominant-negative form of PKCalpha implicated PKCalpha and RhoA activation in these events. Therefore, combined interaction of the astrocyte alphavbeta3-integrin-syndecan-4 receptor pair with Thy-1, promotes adhesion to the underlying matrix via PKCalpha- and RhoA-dependent pathways. Importantly, signaling events triggered by such receptor cooperation are shown here to be the consequence of cell-cell rather than cell-matrix interactions. These observations are likely to be of widespread biological relevance because Thy-1-integrin binding is reportedly relevant to melanoma invasion, monocyte transmigration through endothelial cells and host defense mechanisms.

Motivação e desempenho dos funcionários da administração pública cabo-verdiana actual

The process of changes that have been taking place in contemporary world reaches undoubtedly to the public sector. The quest for a new public management, that seeks to provide quality and effective services to the citizens, has been the target of contemporary State. Within this framework, the study of people inside publics organizations becomes strategic. Knowledge is generated, processed, and communicated at great speed, taking society to adopt new approaches. In order to meet the challenges of the new millennium, organizations must thing more of people and, above all, they must be more concerned with creating incentives that can motivate their collaborators to achieve not only the objectives of the organization but also personal objectives of each individual, since there is no point in gaining profit and having productivity if the organization do not develop policies and practices that focus on the human being. Motivation implies accomplishment feelings and professional recognition, expressed by means of executing tasks and activities that are sufficiently challenging and meaningful to the job. The truth is that the adoption of a public management focused on quality requires changes in organization culture, requiring mainly motivation, which leads to efforts, dedication, persistence, and commitment. This work is intended to research motivation as a tool to achieve productivity and excellence in the performance of activities in Cape Verdean Public Administration. To achieve the aim of this work, a bibliographical research on Human Resources Administration as well as different theories related to work motivation in organizations was conducted. The inquisitive method was used based upon a written questionnaire aimed at obtaining data referring to motivation of Public Administration workers.

Motivação e desempenho dos funcionários da administração pública cabo-verdiana actual

O processo de mudanças que vem acontecendo no mundo contemporâneo alcança, inevitavelmente, o sector público. A busca de uma nova gestão pública, que procure prestar serviços ao cidadão com qualidade e eficiência tem sido o alvo a ser alcançado pelo Estado contemporâneo. Dentro desse prisma o estudo das pessoas dentro das organizações públicas apresenta-se como estratégico. O conhecimento é gerado, processado e comunicado a grande velocidade, o que leva a sociedade a assumir novas posturas. Para enfrentar os desafios do novo milénio, as organizações terão que pensar mais nas pessoas e sobretudo, preocupar-se mais em criar estímulos que motivem os colaboradores para alcançarem tanto os objectivos da organização quanto os objectivos pessoais de cada um porque não adianta obter lucro e produtividade se a organização não desenvolver políticas e práticas que privilegiam o ser humano. Motivação envolve sentimentos de realização e de reconhecimento profissional, manifestado por meio de exercícios das tarefas e actividades que oferecem suficiente desafio e significado para o trabalho. A verdade é que a adopção de uma gestão pública focada na qualidade requer mudanças na cultura organizacional, exigindo principalmente motivação, que conduz ao esforço, dedicação, persistência e comprometimento. Com o presente trabalho pretende-se investigar a motivação como uma ferramenta para alcançar a produtividade e a excelência no desempenho das actividades na Administração Pública Cabo-verdiana. Para alcançar o objectivo deste trabalho, fez-se uma pesquisa bibliográfica sobre a Administração dos Recursos Humanos e sobre as diversas teorias relacionadas com a motivação para o trabalho nas organizações. Utilizou-se o método inquisitivo baseado num interrogatório escrito para se obter dados referentes a motivação dos funcionários da Administração Pública.

Deposições rituais de vasos cerâmicos em contextos domésticos: os exemplares do povoado calcolítico fortificado do Outeiro Redondo (Sesimbra)

A identificação de dois recipientes colocados ritualmente em posição invertida, conotáveis com a derradeira fase de ocupação do povoado calcolítico do Outeiro Redondo (Sesimbra), e deste modo com uma cerimónia de abandono do próprio sítio arqueológico, conduziu à procura de exemplos comparáveis. Tal procura estendeu‑se, depois, às evidências de utilização ritual, em contextos habitacionais, de recipientes cerâmicos, desde a época a que pertencem os exemplares em causa, até ao Período Romano. Teve‑se ainda em consideração o contributo da Etnografia e da Arqueologia africana, através da experiência do signatário, relacionada com intervenção arqueológica que dirigiu em unidade doméstica do século XVII/XVIII da ilha de São Vicente (República de Cabo Verde). Sem se pretender assumir a continuidade desta prática ritual no actual território português, desde o Calcolítico até pelo menos à Época Romana, por poder tratar‑se de uma simples convergência, recorrentemente verificada ao longo da Idade do Bronze e do Ferro. Como se deverá interpretar o achado do Outeiro Redondo? As evidências assinaladas através do uso ritual de recipientes cerâmicos em contextos habitacionais podem ter um significado ligado ao próprio quotidiano, como no povoado de Fraga da Pena (Fornos de Algodres). Aquelas afiguram‑se, contudo, mais abundantes e expressivas no que se refere quer às práticas de natureza fundacional, quer às relacionadas com o abandono; por vezes, dada a presença de aves sacrificadas, tais rituais poderiam também revestir uma função propiciatória, que não é incompatível com as duas funções mencionadas, também elas não incompatíveis entre si.

Motivação e desempenho dos funcionários da administração pública cabo-verdiana actual

The process of changes that have been taking place in contemporary world reaches undoubtedly to the public sector. The quest for a new public management, that seeks to provide quality and effective services to the citizens, has been the target of contemporary State. Within this framework, the study of people inside publics organizations becomes strategic. Knowledge is generated, processed, and communicated at great speed, taking society to adopt new approaches. In order to meet the challenges of the new millennium, organizations must thing more of people and, above all, they must be more concerned with creating incentives that can motivate their collaborators to achieve not only the objectives of the organization but also personal objectives of each individual, since there is no point in gaining profit and having productivity if the organization do not develop policies and practices that focus on the human being. Motivation implies accomplishment feelings and professional recognition, expressed by means of executing tasks and activities that are sufficiently challenging and meaningful to the job. The truth is that the adoption of a public management focused on quality requires changes in organization culture, requiring mainly motivation, which leads to efforts, dedication, persistence, and commitment. This work is intended to research motivation as a tool to achieve productivity and excellence in the performance of activities in Cape Verdean Public Administration. To achieve the aim of this work, a bibliographical research on Human Resources Administration as well as different theories related to work motivation in organizations was conducted. The inquisitive method was used based upon a written questionnaire aimed at obtaining data referring to motivation of Public Administration workers.

Deposições rituais de vasos cerâmicos em contextos domésticos: os exemplares do povoado calcolítico fortificado do Outeiro Redondo (Sesimbra)

A identificação de dois recipientes colocados ritualmente em posição invertida, conotáveis com a derradeira fase de ocupação do povoado calcolítico do Outeiro Redondo (Sesimbra), e deste modo com uma cerimónia de abandono do próprio sítio arqueológico, conduziu à procura de exemplos comparáveis. Tal procura estendeu‑se, depois, às evidências de utilização ritual, em contextos habitacionais, de recipientes cerâmicos, desde a época a que pertencem os exemplares em causa, até ao Período Romano. Teve‑se ainda em consideração o contributo da Etnografia e da Arqueologia africana, através da experiência do signatário, relacionada com intervenção arqueológica que dirigiu em unidade doméstica do século XVII/XVIII da ilha de São Vicente (República de Cabo Verde). Sem se pretender assumir a continuidade desta prática ritual no actual território português, desde o Calcolítico até pelo menos à Época Romana, por poder tratar‑se de uma simples convergência, recorrentemente verificada ao longo da Idade do Bronze e do Ferro. Como se deverá interpretar o achado do Outeiro Redondo? As evidências assinaladas através do uso ritual de recipientes cerâmicos em contextos habitacionais podem ter um significado ligado ao próprio quotidiano, como no povoado de Fraga da Pena (Fornos de Algodres). Aquelas afiguram‑se, contudo, mais abundantes e expressivas no que se refere quer às práticas de natureza fundacional, quer às relacionadas com o abandono; por vezes, dada a presença de aves sacrificadas, tais rituais poderiam também revestir uma função propiciatória, que não é incompatível com as duas funções mencionadas, também elas não incompatíveis entre si.

Cape Verdean Creole of São Vicente: Its genesis and Structure

Although the Santiago variety of Cape Verdean Creole (CVC) has been the subject of numerous linguistic works, the second major variety of the language, i.e. the São Vicente variety of CVC (CVSV), has hardly been described. Nevertheless this lack of studies and given its striking differences, on all linguistic levels, from the variety of Santiago (CVST), the implicit explanation for such divergences, echoed for decades in the literature on CVC, has been the presumably decreolized character of CVSV. First, this study provides a comprehensive fieldwork-based synchronic description of CVSV major morpho-syntactic categories in the intent to document the variety. Second, it aims to place the study of CVSV within a broader scope of contact linguistics in the quest to explain its structure. Based on analyses of historical documents and studies, it reconstructs the sociohistorical scenario of the emergence and development of CVSV in the period of 1797- 1975. From the comparison of the current structures of CVSV and CVST, the examination of linguistic data in historical texts and the analysis of sociohistorical facts it becomes clear that the contemporary structure of CVSV stems from the contact-induced changes that occurred during the intensive language and dialect contact on the island of São Vicente in the early days of its settlement in the late 18th and ensuing early 19th century development, rather than from modern day pressure of Portuguese. Although this dissertation argues for multiple explanations rather than a single theory, by showing that processes such as languages shift among the first Portuguese settlers, L2 acquisition, migration of the Barlavento speakers and subsequent dialect leveling as well as language borrowing at a later stage were at stake, it demonstrates the usefulness of partial-restructuring model proposed by Holm (2004).

Male beach workers and western female tourists : livelihood strategies in Kenya's south coast region

Recent years have seen an emerging knowledge base and increasing public interest and awareness of sexual-economic relationships between local men and Western women, in different touristic regions around the world. However, to date, Western perspectives on the phenomenon make up the bulk of the existent literature. Questioning the dominant discourse of 'romance tourism' and representations of male participants as 'victims-opportunists', this dissertation explores male beach workers' experiences with, and perspectives on sexual-economic relationships between Kenyan men and visiting Western women in Kenya's South Coast region. The men were not considered in isolation; their experiences and perspectives are situated in relation to their family ties, social networks and the political economy of beach tourism. The study shows that locally these relationships are clearly understood as livelihood strategies for the visited. Men seek to establish long-term intimate relationships with female tourists as a means to accessing life's basic necessities for themselves and for their families and overall to improve their standards of living. It is argued that these relationships are a response to the poverty and inequalities generated by socio-economic changes over time. They are also a response to local gender role prescriptions that hinge male social value on men's capacity to marry, procreate and provide intergenerational social and economic support. The men's parallel quest for non-sexual economically motivated friendships with visiting foreign tourists termed "family friends" is a salient finding, that serves to reinforce the finding that the sexual- economic relationships are above all livelihood strategies. Résumé Ces dernières années ont vu l'émergence d'une base de connaissance, ainsi que d'un intérêt et d'une prise de conscience accrue du public, à l'égard des relations économico-sexuelles entre hommes locaux et femmes occidentales, dans différentes régions touristiques du monde. Cependant, à ce jour, des perspectives occidentales sur ce phénomène constituent l'essentiel de la littérature existante. En remettant en question le discours dominant du «romance tourism» (tourisme sentimental) et les représentations qui conçoivent les hommes participants comme étant 'victimes-opportunistes', cette thèse explore les expériences, et les visions qu'ont les travailleurs de plage sur les relations économico-sexuelles entre hommes Kenyans et femmes Occidentales dans la région de la côte sud du Kenya. Les hommes n'ont pas été considérés de manière isolée; leurs expériences et leurs perspectives sont situées par rapport à leur liens familiaux, leur réseaux sociaux et aussi par rapport à l'économie politique du tourisme balnéaire. L'étude montre que sur place ces relations sont clairement conçues comme des stratégies de survie pour les participants hôtes. Les hommes cherchent à établir des relations de long durée avec des femmes touristes comme moyen d'accéder à des biens et des services qui constituent des nécessités de bases, pour eux et pour leur familles et globalement pour relever leur niveau de vie! L'étude fait valoir que ces relations sont une réponse à la pauvreté et aux inégalités sociales crées par des dynamiques socio-économiques au fil du temps. Elles sont aussi une réponse au prescriptions sociales locales par lesquelles la valeur sociale masculine est définie à travers la capacité des hommes à se marier, à procréer et d'assurer un soutien intergénérationnel social et économique. La quête, en parallèle, de relations d'amitiés non-sexuelles à motivation économique, dénommé « family friends », par des hommes, est un résultat saillant de cette étude qui vient renforcer l'observation que les relations économico-sexuelles relèvent avant tout des stratégies de survie.

Lentiviral delivery of the human wild-type tau protein mediates a slow and progressive neurodegenerative tau pathology in the rat brain.

Most models for tauopathy use a mutated form of the Tau gene, MAPT, that is found in frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) and that leads to rapid neurofibrillary degeneration (NFD). Use of a wild-type (WT) form of human Tau protein to model the aggregation and associated neurodegenerative processes of Tau in the mouse brain has thus far been unsuccessful. In the present study, we generated an original "sporadic tauopathy-like" model in the rat hippocampus, encoding six Tau isoforms as found in humans, using lentiviral vectors (LVs) for the delivery of a human WT Tau. The overexpression of human WT Tau in pyramidal neurons resulted in NFD, the morphological characteristics and kinetics of which reflected the slow and sporadic neurodegenerative processes observed in sporadic tauopathies, unlike the rapid neurodegenerative processes leading to cell death and ghost tangles triggered by the FTDP-17 mutant Tau P301L. This new model highlights differences in the molecular and cellular mechanisms underlying the pathological processes induced by WT and mutant Tau and suggests that preference should be given to animal models using WT Tau in the quest to understand sporadic tauopathies.

Teologis-filosofista aatehistoriaa uusissa väitöskirjoissa

Simo Knuuttila

Que cache l'agenda caché [What is behind the hidden agenda?]

The physicians often forget to ask their patients if they would like to discuss other complaints or topics. It is sometimes quite difficult to explore the patient's complaints; while the physicians tend to focus on the immediate problem, the patients may have not only one, but several hidden agendas during a visit. In a caring relation there is a clear advantage to clarify the implicit. The search for the hidden agenda is to improve the care of i) biomedical problems ii) the social quest presented to the physicians. The sentence "Oh, by the way, doctor..." should not be only understood as an information but also as a relational expression and a reaction to the imminent separation from the physician.

Robustness of entanglement

In the quest to completely describe entanglement in the general case of a finite number of parties sharing a physical system of finite-dimensional Hilbert space an entanglement magnitude is introduced for its pure and mixed states: robustness. It corresponds to the minimal amount of mixing with locally prepared states which washes out all entanglement. It quantifies in a sense the endurance of entanglement against noise and jamming. Its properties are studied comprehensively. Analytical expressions for the robustness are given for pure states of two-party systems, and analytical bounds for mixed states of two-party systems. Specific results are obtained mainly for the qubit-qubit system (qubit denotes quantum bit). As by-products local pseudomixtures are generalized, a lower bound for the relative volume of separable states is deduced, and arguments for considering convexity a necessary condition of any entanglement measure are put forward.

Analysis of potential transcriptomic biomarkers for Huntington's disease in peripheral blood.

Highly quantitative biomarkers of neurodegenerative disease remain an important need in the urgent quest for disease-modifying therapies. For Huntington's disease (HD), a genetic test is available (trait marker), but necessary state markers are still in development. In this report, we describe a large battery of transcriptomic tests explored as state biomarker candidates. In an attempt to exploit the known neuroinflammatory and transcriptional perturbations of disease, we measured relevant mRNAs in peripheral blood cells. The performance of these potential markers was weak overall, with only one mRNA, immediate early response 3 (IER3), showing a modest but significant increase of 32% in HD samples compared with controls. No statistically significant differences were found for any other mRNAs tested, including a panel of 12 RNA biomarkers identified in a previous report [Borovecki F, Lovrecic L, Zhou J, Jeong H, Then F, Rosas HD, Hersch SM, Hogarth P, Bouzou B, Jensen RV, et al. (2005) Proc Natl Acad Sci USA 102:11023-11028]. The present results may nonetheless inform the future design and testing of HD biomarker strategies.

Aggregation of integrins and RhoA activation are required for Thy-1-induced morphological changes in astrocytes.

Thy-1, a cell adhesion molecule abundantly expressed in mammalian neurons, binds to a beta(3)-containing integrin on astrocytes and thereby stimulates the assembly of focal adhesions and stress fibers. Such events lead to morphological changes in astrocytes that resemble those occurring upon injury in the brain. Extracellular matrix proteins, typical integrin ligands, bind to integrins and promote receptor clustering as well as signal transduction events that involve small G proteins and cytoskeletal changes. Here we investigated the possibility that the cell surface protein Thy-1, when interacting with a beta(3)-containing integrin on astrocytes, could trigger signaling events similar to those generated by extracellular matrix proteins. DI-TNC(1) astrocytes were stimulated with Thy-1-Fc immobilized on beads, and increased RhoA activity was confirmed using an affinity precipitation assay. The effect of various inhibitors on the cellular response was also studied. The presence of Y-27632, an inhibitor of Rho kinase (p160ROCK), a key downstream effector of RhoA, significantly reduced focal adhesion and stress fiber formation induced by Thy-1. Similar effects were obtained when astrocytes were treated with C3 transferase, an inhibitor of RhoA. Alternatively, astrocytes were transfected with an expression vector encoding fusion proteins of enhanced green fluorescent protein with either the Rho-binding domain of Rhotekin, which blocks RhoA function, or the dominant-negative N19RhoA mutant. In both cases, Thy-1-induced focal adhesion formation was inhibited. Furthermore, we observed that RhoA activity after stimulation with soluble Thy-1-Fc molecule was augmented upon further cross-linking using protein A-Sepharose beads. The same was shown by cross-linking beta(3)-containing integrin with anti-beta(3) antibodies. Together, these results indicate that Thy-1-mediated astrocyte stimulation depended on beta(3) integrin clustering and the resulting increase in RhoA activity.