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  • 1
  • 2
    Language: English
    In: The Journal of biological chemistry, 18 September 2015, Vol.290(38), pp.23039-49
    Description: Calcium-binding proteins (CaBPs) such as parvalbumin are part of the cellular calcium buffering system that determines intracellular calcium diffusion and influences the spatiotemporal dynamics of calcium signals. In neurons, CaBPs are primarily localized to the cytosol and function, for example, in nerve terminals in short-term synaptic plasticity. However, CaBPs are also expressed in the cell nucleus, suggesting that they modulate nuclear calcium signals, which are key regulators of neuronal gene expression. Here we show that the calcium buffering capacity of the cell nucleus in mouse hippocampal neurons regulates neuronal architecture by modulating the expression levels of VEGFD and the complement factor C1q-c, two nuclear calcium-regulated genes that control dendrite geometry and spine density, respectively. Increasing the levels of nuclear calcium buffers by means of expression of a nuclearly targeted form of parvalbumin fused to mCherry (PV.NLS-mC) led to a reduction in VEGFD expression and, as a result, to a decrease in total dendritic length and complexity. In contrast, mRNA levels of the synapse pruning factor C1q-c were increased in neurons expressing PV.NLS-mC, causing a reduction in the density and size of dendritic spines. Our results establish a close link between nuclear calcium buffering capacity and the transcription of genes that determine neuronal structure. They suggest that the development of cognitive deficits observed in neurological conditions associated with CaBP deregulation may reflect the loss of necessary structural features of dendrites and spines.
    Keywords: Calcium ; Calcium Binding Protein ; Dendrite ; Gene Expression ; Signal Transduction ; Synapse ; Calcium -- Metabolism ; Dendritic Spines -- Metabolism ; Hippocampus -- Metabolism ; Nerve Net -- Metabolism
    E-ISSN: 1083-351X
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  • 3
    Language: German
    In: Soziale Passagen, 2015, Vol.7(1), pp.145-149
    Description: Das vom Sächsischen Staatsministerium für Wissenschaft und Kunst geförderte Projekt „Soziale Arbeit an sächsischen Hochschulen – ein disziplinäres Kooperationsprojekt zwischen Transfer, Qualifikation und Profilschärfung“ knüpft an die seit zwei Jahrzehnten bestehenden Kooperationen und Arbeitsbündnisse der Technischen Universität Dresden und der Hochschule Mittweida an. Diese sollen konzentriert und optimiert werden – mit dem Ziel des Auf- und Ausbaus nachhaltiger institutionell abgesicherter (Kooperations-) Strukturen in der Sozialen Arbeit an Universität und Fachhochschulen in Sachsen. Gelingt es, eine kooperative Struktur zu schaffen, kann dieser Rahmen maßgeblich zur Durchlässigkeit zwischen den Hochschultypen sowie zur Förderung des wissenschaftlichen Nachwuchses beitragen. Ebenso kann auf diesem Wege eine Profilschärfung in der sächsischen Hochschullandschaft im Bereich Soziale Arbeit erreicht werden. Der Beitrag widmet sich der Vorstellung des Projektes. The project “Social Work at saxon universities and universities of applied sciences–a disciplinal cooperation project between transfer, qualification and profile formation” which is promoted from Saxon State Ministry of Science and Art (Sächsisches Staatsministerium für Wissenschaft und Kunst) goes back to the cooperation and working alliances existing for two decades between the University of Technology Dresden and the University of Applied Sciences Mittweida. These should be concentrated and optimised with the aim of reconstruction and consolidation of institutionally secured (cooperation-) structures with sustainable effect in the field of Social Work at the university and the universities of applied sciences in Saxony. If one succeeds in creating a cooperative structure, this frame can decisively contribute to the permeability between the university types as well as to the promotion of the junior researchers. On this way also a profile formation can be reached in the saxon university scenery in the field of Social Work. The following paper deals with the presentation of the project.
    Keywords: University ; University of applied sciences ; Social work ; Social pedagogy ; Cooperative doctorate
    ISSN: 1867-0180
    E-ISSN: 1867-0199
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  • 4
  • 5
    Language: German
    In: Soziale Passagen, 2009, Vol.1(1), pp.97-101
    Description: Der Artikel gibt einen kurzen Überblick über den Bologna-Prozess in Europa, Deutschland und in der Disziplin Erziehungswissenschaft. Beleuchtet werden hochschul- und wirtschaftspolitische Hintergründe der Studienreform sowie der aktuelle Stand und erste Ergebnisse auf internationaler und nationaler Ebene. Die Entwicklung in der Erziehungswissenschaft wird beschrieben. Aufgegriffen wird dabei die Frage nach der drohenden Deprofessionalisierung durch den Bologna-Prozess, die auch in der erziehungswissenschaftlichen Debatte immer wieder gestellt wird. Mit hilfe der Modelle pädagogischer Professionalität von Oevermann und Koring sowie Niekes Modell pädagogischer Kompetenz können verschiedene Faktoren identifiziert werden, die zu einer Deprofessionalisierung in der Pädagogik führen könnten und anhand der aktuellen Entwicklungen auch nachweisbar sind. Während eine endgültige Aussage über eine Deprofessionalisierung aufgrund der Dynamik des Bologna-Prozesses jedoch noch nicht möglich scheint, können die aufgezeigten Faktoren dazu dienen, den problematischen Entwicklungen entgegenzuwirken und weitere empirische und theoretische Forschung anzuregen. The article gives a short overview about the Bologna Process in Europe, Germany and within the discipline of Educational Science. Backgrounds of the academic reform that are to be found in Higher Education Policy and Economic Policy are mentioned as well as the current status and first results on the international and national level. The trend in the field of Educational Science is described. Thereby the question of the imminent danger of deprofessionalisation due to the Bologna Process, that is being discussed repeatedly also within the Educational Science, is picked up. By using Oevermann’s and Koring’s models of pedagogical professionalism and Nieke’s model of pedagogical competence several factors leading to deprofessionalisation in the field of education can be identified and are getting visible by analyzing the current developments. Due to the dynamism of the Bologna Process a final statement about the question of deprofessionalisation seems not yet possible. However, the shown factors can be usefully to avoid the problematic trends and to inspire further empirical and theoretical research.
    Keywords: Bologna process ; Deprofessionalisation ; Educational science
    ISSN: 1867-0180
    E-ISSN: 1867-0199
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  • 6
    Language: German
    In: Sozial Extra, 2007, Vol.31(3), pp.21-24
    Description: Die Wogen der Bologna-Diskussion schlagen hoch. Worauf beziehen sich die kritischen Argumente? Und gibt es eigentlich auch positive Aspekte des BA-/MA-Systems für die Soziale Arbeit?
    Keywords: Knowledge-based Systems;
    ISSN: 0931-279X
    E-ISSN: 1863-8953
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  • 7
    Language: English
    In: Nature medicine, 2016, Vol.22(11), pp.1314-1320
    Description: Pediatric glioblastoma is one of the most common and most deadly brain tumors in childhood. Using an integrative genetic analysis of 53 pediatric glioblastomas and five in vitro model systems, we identified previously unidentified gene fusions involving the MET oncogene in similar to 10% of cases. These MET fusions activated mitogen-activated protein kinase (MAPK) signaling and, in cooperation with lesions compromising cell cycle regulation, induced aggressive glial tumors in vivo. MET inhibitors suppressed MET tumor growth in xenograft models. Finally, we treated a pediatric patient bearing a MET-fusion-expressing glioblastoma with the targeted inhibitor crizotinib. This therapy led to substantial tumor shrinkage and associated relief of symptoms, but new treatment-resistant lesions appeared, indicating that combination therapies are likely necessary to achieve a durable clinical response
    Keywords: Medicine ; Biology;
    ISSN: 1078-8956
    ISSN: 1546-170x
    E-ISSN: 1546170X
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  • 8
    In: Neuro-Oncology, 2018, Vol. 20(suppl2), pp.i106-i106
    Description: The main challenge in the clinical management of pilocytic astrocytoma (PA) is its unpredictable growth behavior. PA cells are driven into oncogene-induced senescence (OIS) by aberrant MAPK activation. In other senescence models OIS was shown to be regulated and maintained by the senescence-associated secretory phenotype (SASP). In this study, the first patient-derived cell culture model DKFZ-BT66 was used to show presence of the SASP in PA and to analyze its impact on OIS. This model allows for shifting between proliferation and senescence via doxycycline-inducible inhibition of the OIS-relevant p53/RB pathway. Both states were studied using gene-expression profiling (GEP), Western blot, qPCR, ELISA, and automated trypan blue exclusion staining. The GEP shows significant upregulation of SASP factors during OIS in DKFZ-BT66 cells. Conditioned medium of senescent DKFZ-BT66 cells is sufficient to induce growth arrest of proliferating DKFZ-BT66 cells. Upregulation of the SASP factors IL-1B and IL-6 was validated on mRNA and protein levels and both pathways are active during OIS. Stimulation of the IL-1 pathway reduces growth of proliferating DKFZ-BT66 cells. While pharmacological inhibition of single cytokines is not sufficient to overcome growth arrest during OIS, treatment with the anti-inflammatory drug dexamethasone induces regrowth of senescent cells. Overall, the primary PA model provides evidence of the presence of OIS in PA and exhibits increased activity of the SASP during senescence. Our data suggest that the SASP has an important impact on the growth regulation of senescent PA cells. Alteration of SASP factors may result in spontaneous regrowth of senescent PA tumors.
    Keywords: Medicine;
    ISSN: 1522-8517
    E-ISSN: 1523-5866
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  • 9
    Language: English
    In: Nature communications, 11 June 2015, Vol.6, pp.7391
    Description: In vivo functional investigation of oncogenes using somatic gene transfer has been successfully exploited to validate their role in tumorigenesis. For tumour suppressor genes this has proven more challenging due to technical aspects. To provide a flexible and effective method for investigating somatic loss-of-function alterations and their influence on tumorigenesis, we have established CRISPR/Cas9-mediated somatic gene disruption, allowing for in vivo targeting of TSGs. Here we demonstrate the utility of this approach by deleting single (Ptch1) or multiple genes (Trp53, Pten, Nf1) in the mouse brain, resulting in the development of medulloblastoma and glioblastoma, respectively. Using whole-genome sequencing (WGS) we characterized the medulloblastoma-driving Ptch1 deletions in detail and show that no off-targets were detected in these tumours. This method provides a fast and convenient system for validating the emerging wealth of novel candidate tumour suppressor genes and the generation of faithful animal models of human cancer.
    Keywords: Crispr-Cas Systems ; Disease Models, Animal ; Brain Neoplasms -- Genetics ; Gene Knockout Techniques -- Methods ; Glioblastoma -- Genetics ; Medulloblastoma -- Genetics
    E-ISSN: 2041-1723
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  • 10
    Language: German
    In: Psychiatrische Praxis, March 2002, Vol.29(2), pp.83-9
    Description: Development of an instrument to assess patient satisfaction with inpatient psychiatric treatment as one component of quality of care. The TUBB 2000 has been developed in four steps (n = 80; n = 111; n = 104; n = 135) and covers the inpatients' satisfaction with 22 areas of psychiatric care. Three factors were extracted: "atmosphere", "quality of treatment", "autonomy". The relationship to the therapeutic staff was especially important for the patients. Intervention variables had no significant impact on patients' satisfaction. Answers to change oriented questions have been less variable than to a state oriented questions. The construct patients' satisfaction implies many methodological pitfalls. The TUBB 2000 can provide useful change sensitive data of patients' satisfaction with the quality of care in a psychiatric unit. It may help to increase quality of inpatient care in psychiatry.
    Keywords: Patient Admission ; Schizophrenic Psychology ; Patient Satisfaction -- Statistics & Numerical Data ; Quality Assurance, Health Care -- Statistics & Numerical Data ; Schizophrenia -- Therapy
    ISSN: 0303-4259
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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