Frei zugängliche Bildungsressourcen für die Sekundarstufe. Eine Analyse von deutschsprachigen Online-Angeboten und der Entwurf eines "OER Quality Index"

Offene Bildungsressourcen (engl. Open Educational Resources oder kurz OER) finden heutzutage immer mehr Anklang von Seiten der Nutzer/innen, der Anbieter/innen, der Forschungsförderung sowie der Bildungspolitik. Tatsächlich gibt es viele Lehr- und Lernmaterialien für die verschiedensten Schulstufen und Fächer, die auf unterschiedlichsten Webseiten kostenfrei zugänglich sind. Mit dem vorliegenden Beitrag werden die Ergebnisse einer Analyse des Angebots von deutschsprachigen Online-Angeboten für die Sekundarstufe mit einem Schwerpunkt auf österreichische Anbieter vorgestellt. Ein wesentliches Ergebnis ist dabei, dass es sich mehrheitlich nicht um tatsächlich „offene“ Bildungsressourcen handelt, da die rechtlichen Rahmenbedingungen (z.B. Verwendung eines entsprechenden Lizenzmodells) nicht gegeben sind. Neben einem Kriterienkatalog zur Analyse des Angebots wird ein daraus abgeleiteter „OER Quality Index“ vorgestellt und entsprechende Ergebnisse einer detaillierten Analyse von 46 Online-Angeboten präsentiert. (DIPF/Orig.

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

Recombinant Protein L: Production, Purification and Characterization of a Universal Binding Ligand

Protein L (PpL) is a universal binding ligand that can be used for the detection and purification of antibodies and antibody fragments. Due to the unique interaction with immunoglobulin light chains, it differs from other affinity ligands, like protein A or G. However, due to its current higher market price, PpL is still scarce in applications. In this study, we investigated the recombinant production and purification of PpL and characterized the product in detail. We present a comprehensive roadmap for the production of the versatile protein PpL in E. coli

Epidermal Langerhans Cells Rapidly Capture and Present Antigens from C-Type Lectin-Targeting Antibodies Deposited in the Dermis

Antigen-presenting cells can capture antigens that are deposited in the skin, including vaccines given subcutaneously. These include different dendritic cells (DCs) such as epidermal Langerhans cells (LCs), dermal DCs, and dermal langerin+ DCs. To evaluate access of dermal antigens to skin DCs, we used mAb to two C-type lectin endocytic receptors, DEC-205/CD205 and langerin/CD207. When applied to murine and human skin explant cultures, these mAbs were efficiently taken up by epidermal LCs. In addition, anti-DEC-205 targeted langerin+ CD103+ and langerin− CD103− mouse dermal DCs. Unexpectedly, intradermal injection of either mAb, but not isotype control, resulted in strong and rapid labeling of LCs in situ, implying that large molecules can diffuse through the basement membrane into the epidermis. Epidermal LCs targeted in vivo by ovalbumin-coupled anti-DEC-205 potently presented antigen to CD4+ and CD8+ T cells in vitro. However, to our surprise, LCs targeted through langerin were unable to trigger T-cell proliferation. Thus, epidermal LCs have a major function in uptake of lectin-binding antibodies under standard vaccination conditions

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

Mitochondrial Haplogroups, Control Region Polymorphisms and Malignant Melanoma: A Study in Middle European Caucasians

Because mitochondria play an essential role in energy metabolism, generation of reactive oxygen species (ROS), and apoptosis, sequence variation in the mitochondrial genome has been postulated to be a contributing factor to the etiology of multifactorial age-related diseases, including cancer. The aim of the present study was to compare the frequencies of mitochondrial DNA (mtDNA) haplogroups as well as control region (CR) polymorphisms of patients with malignant melanoma (n = 351) versus those of healthy controls (n = 1598) in Middle Europe.Using primer extension analysis and DNA sequencing, we identified all nine major European mitochondrial haplogroups and known CR polymorphisms. The frequencies of the major mitochondrial haplogroups did not differ significantly between patients and control subjects, whereas the frequencies of the one another linked CR polymorphisms A16183C, T16189C, C16192T, C16270T and T195C were significantly higher in patients with melanoma compared to the controls. Regarding clinical characteristics of the patient cohort, none of the nine major European haplogroups was associated with either Breslow thickness or distant metastasis. The CR polymorphisms A302CC-insertion and T310C-insertion were significantly associated with mean Breslow thickness, whereas the CR polymorphism T16519C was associated with metastasis.Our results suggest that mtDNA variations could be involved in melanoma etiology and pathogenesis, although the functional consequence of CR polymorphisms remains to be elucidated

Evaluating the Evidence for Transmission Distortion in Human Pedigrees

Children of a heterozygous parent are expected to carry either allele with equal probability. Exceptions can occur, however, due to meiotic drive, competition among gametes, or viability selection, which we collectively term “transmission distortion” (TD). Although there are several well-characterized examples of these phenomena, their existence in humans remains unknown. We therefore performed a genome-wide scan for TD by applying the transmission disequilibrium test (TDT) genome-wide to three large sets of human pedigrees of European descent: the Framingham Heart Study (FHS), a founder population of European origin (HUTT), and a subset of the Autism Genetic Resource Exchange (AGRE). Genotyping error is an important confounder in this type of analysis. In FHS and HUTT, despite extensive quality control, we did not find sufficient evidence to exclude genotyping error in the strongest signals. In AGRE, however, many signals extended across multiple SNPs, a pattern highly unlikely to arise from genotyping error. We identified several candidate regions in this data set, notably a locus in 10q26.13 displaying a genome-wide significant TDT in combined female and male transmissions and a signature of recent positive selection, as well as a paternal TD signal in 6p21.1, the same region in which a significant TD signal was previously observed in 30 European males. Neither region replicated in FHS, however, and the paternal signal was not visible in sperm competition assays or as allelic imbalance in sperm. In maternal transmissions, we detected no strong signals near centromeres or telomeres, the regions predicted to be most susceptible to female-specific meiotic drive, but we found a significant enrichment of top signals among genes involved in cell junctions. These results illustrate both the potential benefits and the challenges of using the TDT to study transmission distortion and provide candidates for investigation in future studies

The Mitochondrial T16189C Polymorphism Is Associated with Coronary Artery Disease in Middle European Populations

BACKGROUND: The pivotal role of mitochondria in energy production and free radical generation suggests that the mitochondrial genome could have an important influence on the expression of multifactorial age related diseases. Substitution of T to C at nucleotide position 16189 in the hypervariable D-loop of the control region (CR) of mitochondrial DNA (mtDNA) has attracted research interest because of its suspected association with various multifactorial diseases. The aim of the present study was to compare the frequency of this polymorphism in the CR of mtDNA in patients with coronary artery disease (CAD, n = 482) and type 2 diabetes mellitus (T2DM, n = 505) from two study centers, with healthy individuals (n = 1481) of Middle European descent in Austria. METHODOLOGY AND PRINCIPAL FINDINGS: CR polymorphisms and the nine major European haplogroups were identified by DNA sequencing and primer extension analysis, respectively. Frequencies and Odds Ratios for the association between cases and controls were calculated. Compared to healthy controls, the prevalence of T16189C was significantly higher in patients with CAD (11.8% vs 21.6%), as well as in patients with T2DM (11.8% vs 19.4%). The association of CAD, but not the one of T2DM, with T16189C remained highly significant after correction for age, sex and body mass index (BMI) and was independent of the two study centers. CONCLUSIONS AND SIGNIFICANCE: Our results show for the first time a significant association of T16189C with CAD in a Middle European population. As reported in other studies, in patients with T2DM an association with T16189C in individuals of European decent remains questionable

Benefits of outdoor sports for society. A systematic literature review and reflections on evidence

The combination of physical activity and being in nature is recognized as providing a range of significant benefits. The objective of this literature review was to compile an overview of the social benefits and costs associated with outdoor sports within the academic literature and to reflect on the quality of underlying evidence that supports the relationship. A systematic review was carried out with seven partners from different European countries, including Bulgaria, France, Germany, United Kingdom, Italy, Portugal, and Spain. From a total of 17,560 studies identified, 133 studies were selected with relevant data extracted to standardized forms. The selected studies have been analyzed with qualitative research methods. A meta-analysis could not be conducted due to the heterogeneity of the study designs and outcome measures. As a result, the review gives an overview of the social impacts associated with outdoor sports which have been clustered to six broad categories: physical health, mental health and wellbeing, education and lifelong learning, active citizenship, crime reduction, and anti-social behavior, as well as additional benefits. The review furthermore revealed gaps in the evidence base which are especially notable in the long-term effects that outdoor sports can have on personal and social development

Threonine utilization is high in the intestine of piglets

The whole-body threonine requirement in parenterally fed piglets is substantially lower than that in enterally fed piglets, indicating that enteral nutrition induces intestinal processes in demand of threonine. We hypothesized that the percentage of threonine utilization for oxidation and intestinal protein synthesis by the portal-drained viscera (PDV) increases when dietary protein intake is reduced. Piglets (n = 18) received isocaloric normal or protein-restricted diets. After 7 h of enteral feeding, total threonine utilization, incorporation into intestinal tissue, and oxidation by the PDV, were determined with stable isotope methodology [U-(13)C threonine infusion]. Although the absolute amount of systemic and dietary threonine utilized by the PDV was reduced in protein-restricted piglets, the percentage of dietary threonine intake utilized by the PDV did not differ between groups (normal protein 91% vs. low protein 85%). The incorporation of dietary threonine into the proximal jejunum was significantly different compared with the other intestinal segments. Dietary, rather than systemic threonine was preferentially utilized for protein synthesis in the small intestinal mucosa in piglets that consumed the normal protein diet (P < 0.05). Threonine oxidation by the PDV was limited during normal protein feeding. In protein-restricted pigs, half of the total whole-body oxidation occurred in the PDV. We conclude that, in vivo, the PDV have a high obligatory visceral requirement for threonine. The high rate of intestinal threonine utilization is due mainly to incorporation into mucosal protein