Lim1, an embryonal transcription factor, is absent in multicystic renal dysplasia, but reactivated in nephroblastomas

OBJECTIVE: Lim1 (Lim homeobox 1) plays an important role during rodent renal development; however, its rolein human kidney development and disease is still unclear. METHODS: We investigated LIM1 expression during human renal development, in dysplastic kidneys and in renal neoplasms using immunohistochemistry. RNA levels in renal carcinomas were determined by quantitative RT-PCR, and the potential roles of LIM1 in mesenchymal-epithelial transition and cell cycle were investigated in a cell culture model. RESULTS: LIM1 was detected in pretubular aggregates, S-shaped and comma-shaped bodies as well as immature glomeruli between 10 and 30 weeks of gestation. Eleven dysplastic kidneys showed no expression of LIM1. In contrast, 12 of 32 nephroblastomas showed nuclear positivity. One regressive nephroblastoma had diffuse expression of LIM1 in tubular structures, all others showed focal positivity in mesenchymal, blastemal and epithelial structures. Renal cell carcinomas revealed no expression of LIM1. Overexpression of LIM1 in a cell culture model led to an increase in KERATIN7 expression but no change in the cell cycle. CONCLUSION: Our study supports the concept of a causative role of LIM1 deficiency in the development of multicystic kidney. In a small subset of nephroblastomas with a more diffuse expression pattern LIM1 might also contribute to the pathogenesis of these lesions

Loss of PTEN/MMAC1 activity is a rare and late event in the pathogenesis of nephroblastomas.

Recent genetic investigations of nephroblastomas point to an activation of the Wnt pathway. Data indicate however that activation might be partly due to cross talk of different signaling pathways including the tumor suppressor gene PTEN (phosphatase and tensin homolog on chromosome 10). Therefore, we examined expression and chromosomal aberrations of PTEN in nephroblastomas of different subtypes and the corresponding nephrogenic rests. Loss of heterozygosity was analyzed by high-resolution melting analysis of 4 different single nucleotide polymorphisms. Results were confirmed by sequence analysis of the polymerase chain reaction products. In addition, an intragenic insertion-deletion polymorphism of the PTEN gene was investigated. Protein expression was assessed by immunohistochemistry. Twenty-two nephroblastomas and their corresponding nephrogenic rests were included in the study. In the high-resolution melting analysis, 15 samples were homozygous, 6 were heterozygous, and for 1 sample results could not be obtained for technical reasons. None of the samples showed loss of heterozygosity. Nineteen of the tumors and corresponding nephrogenic rests were also examined immunohistochemically. All tumors showed cytoplasmic positivity, with the exception of 1 tumor that showed complete loss of staining. In 1 tumor, the epithelial component showed distinct cytoplasmic staining, whereas the immature muscle and hyaline cartilage were negative. All nephrogenic rests exhibited positive cytoplasmic staining of all components. Our results establish that inactivation of PTEN is a rare and late event in the pathogenesis of nephroblastomas

LXR-Agonists Regulate ApoM Expression Differentially in Liver and In- testine

Abstract: Apolipoprotein M (apoM) has been suggested to play a role in reverse cholesterol transport. Here we studied the influence of liver X-receptor (LXR) agonist on the transcriptional regulation of apoM. Studies were performed in murine liver and intestinal mucosal cells in vivo and in human intestinal Caco-2 cells in vitro. The expression of apoM was analyzed by quantitative real time PCR, and compared to well-established LXR target genes. Mice fed with TO901317 for six days showed a downregulation of apoM and apoAI in the liver to 40 % and 60 % respectively and an upregulation of Cyp7A1 to 280 %. In the small intestine, however, apoM and apoAI were upregulated by 30-60 % and ABCA1 by 250-430 %. In Caco-2 cells TO901317 caused a 60 % upregulation and the natural LXR agonist 22-hydroxycholesterol a 40 % upregulation of apoM. Possible causes for the differential effects in liver and intestine are discussed

MOOC creation in adult education. Recommendations for creating and implementing online courses for many people

Auf der österreichischen MOOC-Plattform iMooX.at werden seit 2014 zahlreiche offene Online-Kurse angeboten. Für den vorliegenden Beitrag haben ExpertInnen - dabei handelt es sich um die Verantwortlichen für eine reiche Palette an unterschiedlichen Erwachsenenbildungs-MOOCs mit insgesamt etwa 21.000 registrierten TeilnehmerInnen - ihre Erfahrungen mit MOOCs systematisch zusammengetragen. Sie formulieren Empfehlungen, die für ErwachsenenbildnerInnen bei der Konzeption und Durchführung eines großen, offenen Online-Kurses hilfreich sein könnten. Außerdem enthält der Beitrag sowohl Überlegungen zu potenziellen Zielgruppen, Themen und Vorhaben für MOOCs als auch Reflexionen rund um die Herausforderungen bei der MOOC-Konzeption. Schließlich legt das AutorInnenkollektiv dar, wie MOOCs didaktisch ausgestaltet werden sollten, um die Lernenden optimal zu unterstützen. (DIPF/Orig.)Since 2014 a large number of open online courses have been offered on the Austrian MOOC platform iMooX.at. For this article, experts - those responsible for a rich variety of different adult education MOOCs with a total of around 21,000 registered participants - have systematically collected their experiences with MOOCs. They formulate recommendations that may help adult educators create and implement a massive open online course. The article also includes thoughts on potential target groups, topics and plans for MOOCs as well as reflections on the challenges involved in creating a MOOC. Finally, the experts\u27 collective explains how MOOCs should be designed in terms of didactics so that learners receive optimal support. (DIPF/Orig.

Diversity of Staphylococcus aureus Isolates in European Wildlife

Staphylococcus aureus is a well-known colonizer and cause of infection among animals and it has been described from numerous domestic and wild animal species. The aim of the present study was to investigate the molecular epidemiology of S. aureus in a convenience sample of European wildlife and to review what previously has been observed in the subject field. 124 S. aureus isolates were collected from wildlife in Germany, Austria and Sweden; they were characterized by DNA microarray hybridization and, for isolates with novel hybridization patterns, by multilocus sequence typing (MLST). The isolates were assigned to 29 clonal complexes and singleton sequence types (CC1, CC5, CC6, CC7, CC8, CC9, CC12, CC15, CC22, CC25, CC30, CC49, CC59, CC88, CC97, CC130, CC133, CC398, ST425, CC599, CC692, CC707, ST890, CC1956, ST2425, CC2671, ST2691, CC2767 and ST2963), some of which (ST2425, ST2691, ST2963) were not described previously. Resistance rates in wildlife strains were rather low and mecA-MRSA isolates were rare (n = 6). mecC-MRSA (n = 8) were identified from a fox, a fallow deer, hares and hedgehogs. The common cattle- associated lineages CC479 and CC705 were not detected in wildlife in the present study while, in contrast, a third common cattle lineage, CC97, was found to be common among cervids. No Staphylococcus argenteus or Staphylococcus schweitzeri-like isolates were found. Systematic studies are required to monitor the possible transmission of human- and livestock- associated S. aureus/MRSA to wildlife and vice versa as well as the possible transmission, by unprotected contact to animals. The prevalence of S. aureus/MRSA in wildlife as well as its population structures in different wildlife host species warrants further investigation

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

„Ein Lehrer ist wie…“: Mit welchen Metaphern umschreiben Studierende der Wirtschaftspädagogik die Tätigkeit von Lehrpersonen?

Im Rahmen der Lehr-Lernforschung wird untersucht, wie Lehr-Lernprozesse ablaufen und durch welche Phänomene sie beeinflusst werden. Eine bedeutsame Einflussgröße wird in den Wahrnehmungen der handelnden Akteure gesehen, die wiederum durch Vorwissen, Erfahrungen und Überzeugungen bestimmt werden. [...] Im Fokus der nachfolgend dargestellten Arbeiten stehen erste Prüfungen der Tauglichkeit des Werkzeugs \u27Metapher\u27. Mit den Arbeiten wird insgesamt das Ziel angestrebt, Aussagen über die Beziehung metaphorischer Umschreibungen der Tätigkeit von Lehrpersonen und unterrichtlichem Handeln treffen zu können. Falls Metaphern substanzielle Handlungsbedeutsamkeit zukommt, wären mögliche Konsequenzen für die Qualifizierung von Lehrpersonen zu prüfen. (DIPF/Orig.

Metaphors as tool of inquiry: Detecting the different views of pre-service and in-service teachers

One of the most important challenges in education is to recruit and qualify the most eligible persons for the demanding job “teacher” to assure a high quality of instructional activities. Therefore, it seems to be worthwhile trying to get clues of prospective teaching behavior before admission or in an early stage of qualifying respectively. According to the Cognitive Theory of the Metaphor (Lakoff & Johnson, 1980), metaphors are influential mental models. There is some evidence that they regulate how we perceive, think, and act. Thus, a reliable and valid metaphor-based instrument could be helpful for getting such clues concerning student teachers’ prospective instructional activities efficiently. The aim of the study to be presented is to validate our step-by-step developed tool of inquiry using metaphors to describe student teachers’ thinking about instructional activities. Beyond, we investigate significant differences in the selection of metaphors at different stages and circumstances in their teaching career. Students from the area “Economic and Business Education” (n=317) and teachers (n=365) from nine vocational schools completed a questionnaire. The instrument consists of 28 metaphors. Exploratory factor analysis and t-test for independent measures are conducted. 20 metaphors can be classified in four subscales: (1) KNOWLEDGE WORK (α=0.890), (2) SOCIAL SUPPORT (α=0.770), (3) GOAL-/LEARNER-ORIENTATED LEADING (α=0.729), and (4) DETERMINATE & DETERMINATING ACTIVITY (α=0.706), which explained 57.4% of variance. Differences between the views of pre-service and in-service teachers are found. On this account, this predetermined set of metaphors seems to be a useful tool in the above mentioned area of application