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  • 1
    Language: English
    In: American Behavioral Scientist, November 2018, Vol.62(12), pp.1715-1734
    Description: The article presents the aims, approaches, and activities of German social welfare foundations and how they position themselves toward other actors in the field of social welfare provision. The field is characterized by competition and the opening up of the system to deal with the societal challenges of increased demand heterogeneity through migration and demographic changes. Differences in size and approach of the foundations are the main focus and reveal a different understanding and fit toward the challenges of changing demand between old and new subsidiarity. Besides the mutual identity of social foundations in aiming at relief, the large operating foundations more often identify with change, they act complementary and more often consider other actors as important for their work. The small foundations in the field have a charitable–substitutive self-conception.
    Keywords: Philanthropic Foundations ; Social Welfare ; Subsidiarity ; Germany ; Social Sciences (General) ; Psychology
    ISSN: 0002-7642
    E-ISSN: 1552-3381
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  • 2
    Language: English
    In: Cancer Research, 04/15/2012, Vol.72(8 Supplement), pp.4915-4915
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
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  • 3
    Language: English
    In: American Behavioral Scientist, November 2018, Vol.62(12), pp.1639-1669
    Description: The article presents the findings of a research project on the roles and positioning of foundations in Germany, with a focus on the fields of education, higher education, social services, and arts and culture. Results show that fields as well as differences in size and mode of operation are key to understanding the roles and positioning of foundations. Germany is a coordinated market economy with a conservative welfare regime and a corporatist nonprofit sector. However, especially the latter of the two characteristics is gradually changing, and foundations are moving away from a state orientation toward a greater civil society focus.
    Keywords: Philanthropic Foundations ; Germany ; Roles ; Nonprofit ; Welfare Regime ; Social Sciences (General) ; Psychology
    ISSN: 0002-7642
    E-ISSN: 1552-3381
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  • 4
    Language: English
    In: Biochimica et biophysica acta, September 2014, Vol.1842(9), pp.1333-9
    Description: The potential role of the posttranslational modification of proteins with O-linked N-acetyl-β-d-glucosamine (O-GlcNAc) in the pathogenesis of Alzheimer disease (AD) has been studied extensively, yet the exact function of O-GlcNAc in AD remains elusive. O-GlcNAc cycling is facilitated by only two highly conserved enzymes: O-GlcNAc transferase (OGT) catalyzes the addition, while O-GlcNAcase (OGA) catalyzes the removal of GlcNAc from proteins. Studies analyzing global O-GlcNAc levels in AD brain have produced inconsistent results and the reasons for altered O-GlcNAcylation in AD are still poorly understood. In this study, we show a 1.2-fold increase in cytosolic protein O-GlcNAc modification in AD brain when compared to age-matched controls. Interestingly, O-GlcNAc changes seem to be attributable to differential modification of a few individual proteins. While our finding of augmented O-GlcNAcylation concurs with some reports, it is contrary to others demonstrating decreased O-GlcNAc levels in AD brain. These conflicting results emphasize the need for further studies providing conclusive evidence on the subject of O-GlcNAcylation in AD. We further demonstrate that, while OGT protein levels are unaffected in AD, OGA protein levels are significantly decreased to 75% of those in control samples. In addition, augmented protein O-GlcNAc modification correlates to decreased OGA protein levels in AD subjects. While OGA inhibitors are already being tested for AD treatment, our results provide a strong indication that the general subject of O-GlcNAcylation and specifically its regulation by OGA and OGT in AD need further investigation to conclusively elucidate its potential role in AD pathogenesis and treatment.
    Keywords: Alzheimer Disease ; O-Glcnac ; O-Glcnacase ; Acetylglucosamine -- Metabolism ; Alzheimer Disease -- Metabolism ; Brain -- Metabolism ; N-Acetylglucosaminyltransferases -- Metabolism ; Beta-N-Acetylhexosaminidases -- Metabolism
    ISSN: 0006-3002
    ISSN: 09254439
    E-ISSN: 1879260X
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  • 5
    In: PROTEOMICS, November 2013, Vol.13(21), pp.3131-3144
    Description: Growth factor receptor mediated signaling is meanwhile recognized as a complex signaling network, which is initiated by recruiting specific patterns of adaptor proteins to the intracellular domain of epidermal growth factor receptor (. Approaches to globally identify ‐binding proteins are required to elucidate this network. We affinity‐purified with its interacting proteins by coprecipitation from lysates of A431 cells. A total of 183 proteins were repeatedly detected in high‐resolution measurements. For 15 of these, direct interactions with were listed in the iefIndex interaction database, including rb2, shc‐1, 1 and 2, 1 and 3, 2, 3, and . The newly developed ytoscape plugin oduleraph allowed retrieving and visualizing 93 well‐described protein complexes that contained at least one of the proteins found to interact with in our experiments. Abundances of 14 proteins were modulated more than twofold upon activation whereof clathrin‐associated adaptor complex ‐2 showed 4.6‐fold enrichment. These proteins were further annotated with different cellular compartments. Finally, interactions of ‐2 proteins and the newly discovered interaction of 2 could be verified. In conclusion, a powerful technique is presented that allowed identification and quantitative assessment of the interactome to provide further insight into signaling.
    Keywords: Bioinformatics ; Global Protein Analysis ; High Resolution Proteomics ; Interaction Profiling ; Protein Complexes ; Systems Biology
    ISSN: 1615-9853
    E-ISSN: 1615-9861
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  • 6
    Language: English
    In: Biochimica et biophysica acta, August 2014, Vol.1842(8), pp.1248-57
    Description: The initiation and progression of Alzheimer disease (AD) is a complex process not yet fully understood. While many hypotheses have been provided as to the cause of the disease, the exact mechanisms remain elusive and difficult to verify. Proteomic applications in disease models of AD have provided valuable insights into the molecular basis of this disorder, demonstrating that on a protein level, disease progression impacts numerous cellular processes such as energy production, cellular structure, signal transduction, synaptic function, mitochondrial function, cell cycle progression, and proteasome function. Each of these cellular functions contributes to the overall health of the cell, and the dysregulation of one or more could contribute to the pathology and clinical presentation in AD. In this review, foci reside primarily on the amyloid β-peptide (Aβ) induced oxidative stress hypothesis and the proteomic studies that have been conducted by our laboratory and others that contribute to the overall understanding of this devastating neurodegenerative disease.
    Keywords: Alzheimer Disease ; Amyloid-Β ; Methionine-35 ; Oxidative Stress ; Redox Proteomics ; Oxidative Stress ; Proteomics ; Alzheimer Disease -- Metabolism ; Amyloid Beta-Peptides -- Metabolism
    ISSN: 0006-3002
    ISSN: 09254439
    E-ISSN: 1879260X
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  • 7
    Language: English
    In: International Journal of Oncology, Vol.52(4), pp.1117-1128
    Description: Driven by genetic and epigenetic alterations, progression, therapy resistance and metastasis are frequent events in colorectal cancer (CRC). Although often speculated, the function of cell-cell contact for radiochemosensitivity, particularly associated with E-cadherin/catenin complex, warrants further clarification. In this study, we investigated the role of the E-cadherin/catenin complex proteins under more physiological three-dimensional (3D) cell culture conditions in a panel of CRC cell lines. In contrast to floating spheroids and growth in the laminin-rich matrix, collagen type 1 induced the formation of two distinct growth phenotypes, i.e., cell groups and single cells, in 5 out of the 8 CRC cell lines. Further characterization of these subpopulations revealed that, intriguingly, cell-cell contact proteins are important for invasion, but negligible for radiochemosensitivity, proliferation and adhesion. Despite the generation of genomic and transcriptomic data, we were unable to elucidate the mechanisms through which α-catenin affects collagen type 1 invasion. In a retrospective analysis of patients with rectal carcinoma, a low α-catenin expression trended with overall survival, as well as locoregional and distant control. Our results suggest that the E-cadherin/catenin complex proteins forming cell-cell contacts are mainly involved in the invasion, rather than the radiochemosensitivity of 3D grown CRC cells. Further studies are warranted in order to provide a better understanding of the molecular mechanisms controlling cell-cell adhesion in the context of radiochemoresistance.
    Keywords: Colorectal Cancer ; Α-Catenin ; Radiochemotherapy ; E-Cadherin
    ISSN: 1019-6439
    E-ISSN: 1791-2423
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  • 8
    In: Applied Immunohistochemistry & Molecular Morphology, 2016, Vol.24(6), pp.414-421
    Description: Although basal cell carcinomas (BCC) show typical histomorphologic features, they sometimes remain difficult in distinction from benign adnexal skin tumors of follicular origin like trichoepithelioma (TE) or trichoblastoma (TB). Consequently, an immunohistochemical marker panel separating described entities would be helpful in clinical routine. Thus, we stained 22 skin lesions (BCC, TE, and TB) against β-catenin, CK20, E-cadherin, p40, and p63. The staining pattern was described and quantified using an immunohistochemical score. Although p40 and p63 revealed a strong staining intensity of all skin lesions without distinction between BCC and benign lesions (P=1.000), established Merkel cell marker CK20 illustrated a loss of staining in BCC compared with TE and TB (P=0.007). In contrast, BCC exhibited an increased expression of E-cadherin in relation to TE and TB (P=0.009). Single application of CK20 or E-cadherin could predict diagnosis of BCC in 81.8% or 72.7%, respectively. Combining consecutive staining of E-cadherin and CK20 could even enhance specificity toward diagnosis of TE or TB. Hence, findings of our study imply that sequential staining of CK20 and E-cadherin prevents false-positive classification of BCC. Furthermore, our study demonstrated that p40 exhibits the same staining pattern in BCC, TE, and TB. Therefore, p40 might replace p63 equivalently establishing diagnosis of primary adnexal neoplasms of the skin in the form of BCC as well as benign adnexal tumors. As a result, the depicted immunohistochemical marker panel may be applied for adnexal skin neoplasms as a diagnostic adjunct especially in surgically challenging body regions.
    Keywords: Basal Cells ; Skin Diseases ; Trichoepithelioma ; Tumors ; Immunohistochemistry ; E-Cadherin ; Carcinoma ; Benign ; Methods ; Ck20 ; E-Cadherin ; P40 ; Basal Cell Carcinoma ; Trichoblastoma;
    ISSN: 1541-2016
    E-ISSN: 15334058
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  • 9
    Language: English
    In: Bioengineered, 01 May 2013, Vol.4(3), pp.172-179
    Description: The anti-inflammatory cytokine interleukin-10 and its viral homologs were chosen as model proteins for the development of drug delivery systems based on probiotic carriers like E. coli Nissle 1917, E. coli G3/10, and Saccharomyces boulardii. Exterior cytokine secretion was achieved by a modified E. coli hemolysin transporter. Release of interleukin-10 transported to the periplasm via the OmpF signal peptide was enabled by a T4 phage lysis system under control of the araC PBAD activator-promoter. The yield of interleukin-10 delivered by the phage lysis system was too low for functional analysis whereas the fusion protein secreted by the hemolysin transporter proved to be biologically inactive. Moreover, partial processing of the fusion protein by the E. coli membrane protease OmpT had no effect on the protein's functionality. Using the α-mating factor signal sequence, the yeast S. boulardii proved to be suitable for secretory expression of biologically active viral interleukin-10.
    Keywords: Escherichia Coli ; Saccharomyces Boulardii ; Interleukin-10 ; Probiotics ; Hemolysin A ; Transport System ; Bacterial Cell Lysis ; Biological Containment ; Engineering
    ISSN: 2165-5979
    E-ISSN: 2165-5987
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  • 10
    In: FEBS Journal, December 2012, Vol.279(23), pp.4398-4409
    Description: The neural cell adhesion molecule NCAM is involved in neural development and in plasticity in the adult brain. Intracellular trafficking of NCAM is regulated by its ubiquitination. Here we show that ubiquitination of NCAM is regulated by the de‐ubiquitinating enzyme ubiquitin C‐terminal hydrolase L1 (UCHL1) and that UCHL1 overexpression regulates recycling of NCAM to the cell surface
    Keywords: Cytosolic Interaction Partner Of ; Intracellular Trafficking ; Neural Cell Adhesion Molecule ; Ubiquitin C‐Terminal Hydrolase 1 ; Ubiquitination
    ISSN: 1742-464X
    E-ISSN: 1742-4658
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