2,491 research outputs found

    The Structure of the American Civic Sphere

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    Book review: The Civic Constitution: Civic Visions and Struggles in the Path toward Constitutional Democracy. By Elizabeth Beaumont. Oxford University Press, 2014. Pp. xvi + 343. Peopling the Constitution. By John E. Finn. University Press of Kansas, 2014. Pp. xv + 350 Reviewed by Mariah Zeisber

    The Structure of the American Civic Sphere

    Get PDF
    Book review: The Civic Constitution: Civic Visions and Struggles in the Path toward Constitutional Democracy. By Elizabeth Beaumont. Oxford University Press, 2014. Pp. xvi + 343. Peopling the Constitution. By John E. Finn. University Press of Kansas, 2014. Pp. xv + 350 Reviewed by Mariah Zeisber

    AGING, HOME OR INSTITUTION? DIFFERENCES IN PSYCHOLOGICAL WELL-BEING AND THE FEELING OF LONELINESS OF INSTITUTIONALIZED AND NON-INSTITUTIONALIZED OLDER PEOPLE

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    Treball Final de Grau en Psicologia. Codi: PS1048. Curs: 2019/2020The increase in life expectancy and the decrease in the birth rate have caused great changes in society. In this sense, an important change has been observed regarding the aging of the population. This research aims to compare the feeling of loneliness and psychological well-being of the institutionalized and non-institutionalized adult population.El aumento de la esperanza de vida y el descenso de la natalidad han hecho que en la sociedad se produzcan grandes cambios. En este sentido, se ha observado un importante cambio en lo que se refiere al envejecimiento de la población. La presente investigación tiene como objetivo comparar la sensación de soledad y bienestar psicológico de la población adulta institucionalizada y no institucionalizada

    CRISPR/Cas Derivatives as Novel Gene Modulating Tools:Possibilities and In Vivo Applications

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    The field of genome editing started with the discovery of meganucleases (e.g., the LAGLIDADG family of homing endonucleases) in yeast. After the discovery of transcription activator-like effector nucleases and zinc finger nucleases, the recently discovered clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated proteins (Cas) system has opened a new window of applications in the field of gene editing. Here, we review different Cas proteins and their corresponding features including advantages and disadvantages, and we provide an overview of the different endonuclease-deficient Cas protein (dCas) derivatives. These dCas derivatives consist of an endonuclease-deficient Cas9 which can be fused to different effector domains to perform distinct in vitro applications such as tracking, transcriptional activation and repression, as well as base editing. Finally, we review the in vivo applications of these dCas derivatives and discuss their potential to perform gene activation and repression in vivo, as well as their potential future use in human therapy

    Endothelial Cells Expressing Endothelial and Mesenchymal Cell Gene Products in Lung Tissue From Patients With Systemic Sclerosis-Associated Interstitial Lung Disease.

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    OBJECTIVE: To examine whether lung endothelial cells (ECs) from patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) express mesenchymal cell-specific proteins and gene transcripts, indicative of the occurrence of endothelial-to-mesenchymal phenotypic transition (EndoMT). METHODS: Lung tissue from 6 patients with SSc-associated pulmonary fibrosis was examined by histopathology and immunohistochemistry. Confocal laser microscopy was utilized to assess the simultaneous expression of EC and myofibroblast molecular markers. CD31+CD102+ ECs were isolated from the lung tissue of 2 patients with SSc-associated ILD and 2 normal control subjects, and the expression of EC and mesenchymal cell markers and other relevant genes was analyzed by quantitative polymerase chain reaction, immunofluorescence microscopy, and Western blotting. RESULTS: Immunohistochemical staining revealed cells expressing the EC-specific marker CD31 in the subendothelial, perivascular, and parenchymal regions of the lungs from all SSc patients. Confocal microscopy identified cells displaying simultaneous expression of von Willebrand factor and α-smooth muscle actin in small and medium-sized arterioles in the SSc lung tissue but not in normal control lungs. CD31+CD102+ ECs isolated from SSc lungs expressed high levels of mesenchymal cell-specific genes (type I collagen, type III collagen, and fibronectin), EC-specific genes (type IV collagen and VE-cadherin), profibrotic genes (transforming growth factor β1 and connective tissue growth factor), and genes encoding EndoMT-related transcription factors (TWIST1 and SNAI2). CONCLUSION: Cells coexpressing EC- and mesenchymal cell-specific molecules are present in the lungs of patients with SSc-associated ILD. CD31+CD102+ ECs isolated from SSc lungs simultaneously expressed mesenchymal cell- and EC-specific transcripts and proteins. Collectively, these observations demonstrate the occurrence of EndoMT in the lungs of patients with SSc-associated ILD

    Stage-specific action of matrix metalloproteinases influences progressive hereditary kidney disease.

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    BackgroundGlomerular basement membrane (GBM), a key component of the blood-filtration apparatus in the in the kidney, is formed through assembly of type IV collagen with laminins, nidogen, and sulfated proteoglycans. Mutations or deletions involving alpha3(IV), alpha4(IV), or alpha5(IV) chains of type IV collagen in the GBM have been identified as the cause for Alport syndrome in humans, a progressive hereditary kidney disease associated with deafness. The pathological mechanisms by which such mutations lead to eventual kidney failure are not completely understood.Methods and findingsWe showed that increased susceptibility of defective human Alport GBM to proteolytic degradation is mediated by three different matrix metalloproteinases (MMPs)--MMP-2, MMP-3, and MMP-9--which influence the progression of renal dysfunction in alpha3(IV)-/- mice, a model for human Alport syndrome. Genetic ablation of either MMP-2 or MMP-9, or both MMP-2 and MMP-9, led to compensatory up-regulation of other MMPs in the kidney glomerulus. Pharmacological ablation of enzymatic activity associated with multiple GBM-degrading MMPs, before the onset of proteinuria or GBM structural defects in the alpha3(IV)-/- mice, led to significant attenuation in disease progression associated with delayed proteinuria and marked extension in survival. In contrast, inhibition of MMPs after induction of proteinuria led to acceleration of disease associated with extensive interstitial fibrosis and early death of alpha3(IV)-/- mice.ConclusionsThese results suggest that preserving GBM/extracellular matrix integrity before the onset of proteinuria leads to significant disease protection, but if this window of opportunity is lost, MMP-inhibition at the later stages of Alport disease leads to accelerated glomerular and interstitial fibrosis. Our findings identify a crucial dual role for MMPs in the progression of Alport disease in alpha3(IV)-/- mice, with an early pathogenic function and a later protective action. Hence, we propose possible use of MMP-inhibitors as disease-preventive drugs for patients with Alport syndrome with identified genetic defects, before the onset of proteinuria

    A New Framing? Constitutional Representation at Philadelphia's National Constitution Center A

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    in Philadelphia orients its representation of the Constitution around the role of "We the People" in the conduct of constitutional politics. The self-presentation of the NCC explicitly connects its participatory interpretation of the Constitution to the interactivity of the museum experience itself, and announces its aspiration that visitors "get involved!" In so doing the NCC draws upon an emerging edge in museum theory that emphasizes the capacity of museums to support political citizenship. Although the museum's aspiration to enact participatory citizenship is laudable, its exhibits-because of their technologies, use of space, and content-subvert, rather than sustain, the participatory ideal

    Light up your life:Einfluss geschlechtsspezifischer Maßnahmen in außerschulischen Lernorten auf MINT-Interesse und Berufswahl

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    Ausgehend von dem zu erwartenden Fachkräftemangel in naturwissenschaftlich-technischen Disziplinen lenkt diese Arbeit den Blick zunächst auf die aktuelle Diskussion über Geschlechterdifferenzen in Schule und Beruf. Neben den möglichen Ursachen werden sowohl aktuelle Maßnahmen und im speziellen die außerschulischen Leuchtturmprojekte der Universität Münster vorgestellt. In den Fokus rückt dann im zweiten Teil der Arbeit das Langzeitprojekt Light up your life als berufsorientierende und Interessen beeinflussende Maßnahme für junge Frauen im MINT-Bereich. Präsentiert werden Inhalte, Ziele und Evaluationsergebnisse. Schließlich wird die Auswertung einer Vergleichsstudie vorgestellt, die mit den Teilnehmerinnen von Light up your life und weiteren ca. 2000 Schülerinnen und Schülern verschiedener Jahrgänge durchgeführt wurde. Die Ergebnisse in Bezug auf die Zielsetzung des Projektes zur Feststellung des Interessenverlaufs in verschiedenen Unterrichtsfächern und Berufsfeldern werden vorgestellt und diskutiert: mit Light up your life wurde eine erfolgreiche geschlechtsspezifische Maßnahme mit positivem Einfluss auf MINT-Interesse und Berufswahl gefunden
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