Beziehungsweise Flüchtlingshilfe - Die (Re-)Produktion erfahrungsbasierter Beziehungen und situierter Transaktionsräume (der Teilhabe) durch Praktiken ehrenamtlicher Flüchtlingshilfe

The immigration of refugees to EU member states reached a numerical peak in the summer and fall of 2015. At that time, two buzzwords dominated media headlines in Germany: refugee crisis (as a description of the current migration phenomena) and welcome culture. The latter stood for the broad and multifaceted movement of voluntary refugee assistance, which noticeably relieved the organizationally overburdened asylum system in Germany in the reception and integration of refugees and thus made a significant contribution to maintaining social peace. Thus, voluntary refugee relief is not only a meaningful leisure activity or a commendable contribution to society but is always integrated into the public and political debates about the consequences of migration events. Volunteers consequently operate in a highly politicized field, which is becoming increasingly conflictual as the debate about migration and integration intensifies. The present book is dedicated to this dynamic field of civil engagement by presenting and reflecting on the modes of action and negotiation processes of voluntary refugee relief with help of a practice-theoretical perspective. It can be shown that voluntary engagement with refugees is shaped and legitimised in particular with regard to four core aspects: openness and non-commitment, to do moral good, the assumption of social responsibility, and the expectation of a noticeable cultural difference, which together establish practice-field-specific modes of relationship. Furthermore, it becomes clear that the personal relationships between volunteers and refugees in particular can help to counteract the aggravation of asylum law, open up new spaces for participation, and thus contribute to the stability of society as a whole.Die Einreise von Geflüchteten in die Mitgliedsstaaten der EU erreichte einen zahlenmäßigen Höhepunkt im Sommer und Herbst 2015. Zu dieser Zeit prägten in Deutschland zwei Schlagworte die mediale Berichterstattung: Flüchtlingskrise (als Beschreibung der gegenwärtigen Migrationsphänomene) und Willkommenskultur. Letztere stand für die breite und vielschichtige Bewegung ehrenamtlicher Flüchtlingshilfe, die das organisatorisch überforderte Asylsystem Deutschlands bei der Aufnahme und Integration Geflüchteter spürbar entlastete und so vielerorts einen wesentlichen Beitrag zur Aufrechterhaltung des sozialen Friedens leistete. Damit ist ehrenamtliche Flüchtlingshilfe nicht nur eine sinnvolle Freizeitbeschäftigung oder ein lobenswerter Beitrag für die Gesellschaft, sondern immer auch eingebunden in die öffentlichen und politischen Debatten um den Umgang mit und die Konsequenzen von Migrationsereignissen. Die ehrenamtlich Aktiven bewegen sich folglich in einem hoch politisierten Umfeld, welches sich mit der Verschärfung der Diskussion um Migration und Integration zunehmend konfliktreich darstellt. Diesem dynamischen Feld zivilgesellschaftlichen Engagements widmet sich das vorliegende Buch, indem es mit Hilfe einer praxistheoretischen Perspektive die Wirkungsweisen und Aushandlungsprozesse ehrenamtlicher Flüchtlingshilfe dargestellt und reflektiert. Die Analyse des prozessualen Beziehungsgeschehen der Menschen untereinander in und mit ihrer (Um-)Welt zeigt, dass ehrenamtliches Engagement für Geflüchtete insbesondere in Bezug auf die vier zum Teil konfligierenden Kernaspekte der Offenheit und Unverbindlichkeit, des moralisch guten Tuns, der Übernahme gesellschaftlicher Verantwortung und der Erwartung einer erfahrbaren kulturellen Differenz gestaltet und legitimiert wird. Darüber hinaus wird deutlich, dass insbesondere die persönlichen Beziehungen zwischen Ehrenamtlichen und Geflüchteten dazu beitragen können, asylrechtlichen Verschärfungen entgegenzuwirken, neue Teilhaberäume zu eröffnen und damit einen Beitrag zu gesamtgesellschaftlicher Stabilität zu leisten

Repression of human papillomavirus oncogene expression under hypoxia is mediated by PI3K/mTORC2/AKT signaling

Oncogenic HPV types are major human carcinogens. Under hypoxia, HPV-positive cancer cells can repress the viral E6/E7 oncogenes and induce a reversible growth arrest. This response could contribute to therapy resistance, immune evasion, and tumor recurrence upon reoxygenation. Here, we uncover evidence that HPV oncogene repression is mediated by hypoxia-induced activation of canonical PI3K/mTORC2/AKT signaling. AKT-dependent downregulation of E6/E7 is only observed under hypoxia and occurs, at least in part, at the transcriptional level. Quantitative proteome analyses identify additional factors as candidates to be involved in AKT-dependent E6/E7 repression and/or hypoxic PI3K/mTORC2/AKT activation. These results connect PI3K/mTORC2/AKT signaling with HPV oncogene regulation, providing new mechanistic insights into the cross talk between oncogenic HPVs and their host cells.Hypoxia is linked to therapeutic resistance and poor clinical prognosis for many tumor entities, including human papillomavirus (HPV)-positive cancers. Notably, HPV-positive cancer cells can induce a dormant state under hypoxia, characterized by a reversible growth arrest and strong repression of viral E6/E7 oncogene expression, which could contribute to therapy resistance, immune evasion and tumor recurrence. The present work aimed to gain mechanistic insights into the pathway(s) underlying HPV oncogene repression under hypoxia. We show that E6/E7 downregulation is mediated by hypoxia-induced stimulation of AKT signaling. Ablating AKT function in hypoxic HPV-positive cancer cells by using chemical inhibitors efficiently counteracts E6/E7 repression. Isoform-specific activation or downregulation of AKT1 and AKT2 reveals that both AKT isoforms contribute to hypoxic E6/E7 repression and act in a functionally redundant manner. Hypoxic AKT activation and consecutive E6/E7 repression is dependent on the activities of the canonical upstream AKT regulators phosphoinositide 3-kinase (PI3K) and mechanistic target of rapamycin (mTOR) complex 2 (mTORC2). Hypoxic downregulation of E6/E7 occurs, at least in part, at the transcriptional level. Modulation of E6/E7 expression by the PI3K/mTORC2/AKT cascade is hypoxia specific and not observed in normoxic HPV-positive cancer cells. Quantitative proteome analyses identify additional factors as candidates to be involved in hypoxia-induced activation of the PI3K/mTORC2/AKT signaling cascade and in the AKT-dependent repression of the E6/E7 oncogenes under hypoxia. Collectively, these data uncover a functional key role of the PI3K/mTORC2/AKT signaling cascade for viral oncogene repression in hypoxic HPV-positive cancer cells and provide new insights into the poorly understood cross talk between oncogenic HPVs and their host cells under hypoxia

Extractability and Intracellular Localisation of Urea Cycle Enzym es from Rat Liver

Peer Reviewe

Entwicklung von Lehrfilmen zur Gesprächsführung zwischen Realitätsnähe und systematischer didaktischer Gestaltung

Der vorliegende Beitrag beschäftigt sich mit Gestaltungskriterien für Lehrfilme, die im Kontext von Gesprächsführungstrainings eingesetzt werden können. Sie sollten nach der Maßgabe theoretischer Grundlagen oder Modelle systematisch aufgebaut sein und gleichzeitig relevante Kommunikationssituationen realitätsnah darstellen. Hinzu kommt der Anspruch, sie technisch so umzusetzen, dass sie aktuellen Sehgewohnheiten gerecht werden. Ziel dieses Beitrages ist es, entlang dieser Punkte systematische Hinweise für die Realisierung instruktiver Lehrfilme zu geben, die aus Erfahrungen im Projekt ProfKom mit Lehrfilmen zum Arzt-Patienten- und Lehrkraft-Eltern-Gespräch gewonnen wurden. 24.04.2014 | Tobias Hoppe-Seyler, Martin Gartmeier, Grit Möller, Johannes Bauer, Anne Wiesbeck & Gudrun Karsten (Kiel Und München

Enhancer of zeste homolog 2 (EZH2) expression is an independent prognostic factor in renal cell carcinoma

Background: The enhancer of zeste homolog 2 (EZH2) gene exerts oncogene-like activities and its (over)expression has been linked to several human malignancies. Here, we studied a possible association between EZH2 expression and prognosis in patients with renal cell carcinoma (RCC). Methods: EZH2 protein expression in RCC specimens was analyzed by immunohistochemistry using a tissue microarray (TMA) containing RCC tumor tissue and corresponding normal tissue samples of 520 patients. For immunohistochemical assessment of EZH2 expression, nuclear staining quantity was evaluated using a semiquantitative score. The effect of EZH2 expression on cancer specific survival (CSS) was assessed by univariate and multivariate Cox regression analyses. Results: During follow-up, 147 patients (28%) had died of their disease, median follow-up of patients still alive was 6.0 years (range 0 - 16.1 years). EZH2 nuclear staining was present in tumor cores of 411 (79%) patients. A multivariate Cox regression analysis revealed that high nuclear EZH2 expression was an independent predictor of poor CSS (>25-50% vs. 0%: HR 2.72, p = 0.025) in patients suffering from non-metastatic RCC. Apart from high nuclear EZH2 expression, tumor stage and Fuhrman's grading emerged as significant prognostic markers. In metastatic disease, nuclear EZH2 expression and histopathological subtype were independent predictive parameters of poor CSS (EZH2: 1-5%: HR 2.63, p = 0.043, >5-25%: HR 3.35, p = 0.013, >25%-50%: HR 4.92, p = 0.003, all compared to 0%: HR 0.36, p = 0.025, respectively). Conclusions: This study defines EZH2 as a powerful independent unfavourable prognostic marker of CSS in patients with metastatic and non-metastatic RCC

Expression of inhibitor of apoptosis protein Livin in renal cell carcinoma and non-tumorous adult kidney

The antiapoptotic Livin/ML-IAP gene has recently gained much attention as a potential new target for cancer therapy. Reports indicating that livin is expressed almost exclusively in tumours, but not in the corresponding normal tissue, suggested that the targeted inhibition of livin may present a novel tumour-specific therapeutic strategy. Here, we compared the expression of livin in renal cell carcinoma and in non-tumorous adult kidney tissue by quantitative real-time reverse transcription-PCR, immunoblotting, and immunohistochemistry. We found that livin expression was significantly increased in tumours (P=0.0077), but was also clearly detectable in non-tumorous adult kidney. Transcripts encoding Livin isoforms α and β were found in both renal cell carcinoma and normal tissue, without obvious qualitative differences. Livin protein in renal cell carcinoma samples exhibited cytoplasmic and/or nuclear staining. In non-tumorous kidney tissue, Livin protein expression was only detectable in specific cell types and restricted to the cytoplasm. Thus, whereas the relative overexpression of livin in renal cell carcinoma indicates that it may still represent a therapeutic target to increase the apoptotic sensitivity of kidney cancer cells, this strategy is likely to be not tumour-specific

Werner Syndrome Protein (WRN) Regulates Cell Proliferation and the Human Papillomavirus 16 Life Cycle during Epithelial Differentiation

Human papillomaviruses recruit a host of DNA damage response factors to their viral genome to facilitate homologous recombination replication in association with the viral replication factors E1 and E2. We previously demonstrated that SIRT1 deacetylation of WRN promotes recruitment of WRN to E1-E2 replicating DNA and that WRN regulates both the levels and fidelity of E1-E2 replication. The deacetylation of WRN by SIRT1 results in an active protein able to complex with replicating DNA, but a protein that is less stable. Here, we demonstrate an inverse correlation between SIRT1 and WRN in CIN cervical lesions compared to normal control tissue, supporting our model of SIRT1 deacetylation destabilizing WRN protein. We CRISPR/Cas9 edited N/Tert-1 and N/Tert-1+HPV16 cells to knock out WRN protein expression and subjected the cells to organotypic raft cultures. In N/Tert-1 cells without WRN expression, there was enhanced basal cell proliferation, DNA damage, and thickening of the differentiated epithelium. In N/Tert-1+HPV16 cells, there was enhanced basal cell proliferation, increased DNA damage throughout the epithelium, and increased viral DNA replication. Overall, the results demonstrate that the expression of WRN is required to control the proliferation of N/Tert-1 cells and controls the HPV16 life cycle in these cells. This complements our previous data demonstrating that WRN controls the levels and fidelity of HPV16 E1-E2 DNA replication. The results describe a new role for WRN, a tumor suppressor, in controlling keratinocyte differentiation and the HPV16 life cycle

EZH2 Depletion Blocks the Proliferation of Colon Cancer Cells

The Enhancer of Zeste 2 (EZH2) protein has been reported to stimulate cell growth in some cancers and is therefore considered to represent an interesting new target for therapeutic intervention. Here, we investigated a possible role of EZH2 for the growth control of colon cancer cells. RNA interference (RNAi)-mediated intracellular EZH2 depletion led to cell cycle arrest of colon carcinoma cells at the G1/S transition. This was associated with a reduction of cell numbers upon transient transfection of synthetic EZH2-targeting siRNAs and with inhibition of their colony formation capacity upon stable expression of vector-borne siRNAs. We furthermore tested whether EZH2 may repress the growth-inhibitory p27 gene, as reported for pancreatic cancer. However, expression analyses of colon cancer cell lines and colon cancer biopsies did not reveal a consistent correlation between EZH2 and p27 levels. Moreover, EZH2 depletion did not re-induce p27 expression in colon cancer cells, indicating that p27 repression by EZH2 may be cell- or tissue-specific. Whole genome transcriptome analyses identified cellular genes affected by EZH2 depletion in colon cancer cell lines. They included several cancer-associated genes linked to cellular proliferation or invasion, such as Dag1, MageD1, SDC1, Timp2, and Tob1. In conclusion, our results demonstrate that EZH2 depletion blocks the growth of colon cancer cells. These findings might provide benefits for the treatment of colon cancer

A RasGAP SH3 Peptide Aptamer Inhibits RasGAP-Aurora Interaction and Induces Caspase-Independent Tumor Cell Death

The Ras GTPase-activating protein RasGAP catalyzes the conversion of active GTP-bound Ras into inactive GDP-bound Ras. However, RasGAP also acts as a positive effector of Ras and exerts an anti-apoptotic activity that is independent of its GAP function and that involves its SH3 (Src homology) domain. We used a combinatorial peptide aptamer approach to select a collection of RasGAP SH3 specific ligands. We mapped the peptide aptamer binding sites by performing yeast two-hybrid mating assays against a panel of RasGAP SH3 mutants. We examined the biological activity of a peptide aptamer targeting a pocket delineated by residues D295/7, L313 and W317. This aptamer shows a caspase-independent cytotoxic activity on tumor cell lines. It disrupts the interaction between RasGAP and Aurora B kinase. This work identifies the above-mentioned pocket as an interesting therapeutic target to pursue and points its cognate peptide aptamer as a promising guide to discover RasGAP small-molecule drug candidates