The aquaporins

Water is the major component of all living cells, and efficient regulation of water homeostasis is essential for many biological processes. The mechanism by which water passes through biological membranes was a matter of debate until the discovery of the aquaporin water channels. Aquaporins are intrinsic membrane proteins characterized by six transmembrane helices that selectively allow water or other small uncharged molecules to pass along the osmotic gradient. In addition, recent observations show that some aquaporins also facilitate the transport of volatile substances, such as carbon dioxide (CO(2)) and ammonia (NH(3)), across membranes. Aquaporins usually form tetramers, with each monomer defining a single pore. Aquaporin-related proteins are found in all organisms, from archaea to mammals. In both uni- and multicellular organisms, numerous isoforms have been identified that are differentially expressed and modified by post-translational processes, thus allowing fine-tuned tissue-specific osmoregulation. In mammals, aquaporins are involved in multiple physiological processes, including kidney and salivary gland function. They are associated with several clinical disorders, such as kidney dysfunction, loss of vision and brain edema

Cytokeratin 18 expression in immature Sertoli cells: co-localization with interstitial lymphocytic infiltrates.

Although multiple interactions of seminiferous tubules and the interstitial testicular tissue are known, correlation of cytokeratin 18 expressing Sertoli cells with interstitial changes has still not yet been reported. Considering this fact, we focused our investigation on changes of the adjacent interstitial tissue. A total sample of 51 testicular biopsies (from infertile patients) showing mixed atrophy was examined immunohistochemically with antibodies against cytokeratin 18, vimentin, L26/CD20, CD4 and CD8. Twenty-one of the 51 cases showed single seminiferous tubules with Sertoli cells expressing cytokeratin 18. These 21 tubules consistently exhibit either spermatogenic arrest at the level of spermatogonia or only immature Sertoli cells. In the adjacent interstitial tissue of 8 of the 21 cytokeratin 18 positive tubules (39%) striking inflammatory infiltrates--predominantly expressing L26/CD20 typical for B lymphocytes and CD8 typical for T suppressor lymphocytes--were detected. These findings underline that tubules with cytokeratin 18 expressing Sertoli cells exhibit early spermatogenic arrest or only few remaining Sertoli cells. Additionally, we observed a remarkable co-localization of these tubules with lymphocytic infiltrates of the adjacent interstitial tissue

Textüberarbeitung mit Schreibkonferenz oder Textlupe. Zum Einfluss der Schreibumgebung auf die Qualität von Schülertexten

In 16 Klassen mit Schülern des 3. Schuljahres wurde im Rahmen des DFG-Projekts KoText (Kooperative Schülerrückmeldungen bei der Textüberarbeitung im Deutschunterricht der Grundschule) der Einfluss von zwei unterschiedlich strukturierten Schreibumgebungen, Textlupe und Schreibkonferenz, auf die Qualität der Schülertexte untersucht. Analysiert wird die Veränderung der Qualität zwischen dem Entwurf und der Endfassung der Kindertexte (N = 2 x 132). Kovarianzanalysen ergeben, dass sich die Qualität derjenigen Texte, die in der Schreibkonferenz besprochen wurden, positiver entwickelte als die Qualität der Texte, die mit der Textlupe überarbeitet wurden; der Unterschied ist signifikant. Dies gilt jedoch nur für konventionelle Textualitätskriterien (z.B. Kohärenz des Textes), für unkonventionelle Merkmale der Textqualität (inhaltliches und sprachliches Wagnis) zeigte sich kein Effekt der Schreibumgebung. Die Ergebnisse werden hinsichtlich der Verschiedenheit der Strukturiertheit der Schreibumgebungen und der Medialität der Sprachhandlungen diskutiert. (DIPF/Orig.

Zur Qualität von Kindertexten. Entwicklung eines Bewertungsinstruments in der Grundschule

Im Rahmen des Forschungsprojekts "Kooperative Schülerrückmeldungen bei der Textüberarbeitung im Deutschunterricht der Grundschule" wurde ein Ratingsystem entwickelt, mit dessen Hilfe die Qualität von Schülertexten in 10 Dimensionen eingeschätzt wurde. Die herangezogene Stichprobe bestand aus 132 Texten von Schülern des 3. Schuljahres. Die Analysen zeigen in einem ersten Schritt, dass sich die Qualität der Texte auf den 10 unterschiedlichen Dimensionen mit einer hohen Beurteilerübereinstimmung einschätzen ließ. Mittels konfirmatorischer Faktorenanalyse wurde in einem zweiten Schritt die angenommene Modellstruktur überprüft. Die entsprechenden Ergebnisse zeigen, dass das ursprünglich angenommene Modell nicht zu den Daten passte. Daher wurde das Modell modifiziert, indem drei Items aus dem Modell entfernt wurden. Die erneute Überprüfung des reduzierten Modells mit den beiden Faktoren Textualität konventionell und Textualität unkonventionell ergab schließlich einen akzeptablen Modellfit. Der Faktor Textualität konventionell setzt sich aus den Items Kohärenz, Implizitheit und Explizitheit des Textes sowie Wortschatz zusammen aus, der Faktor Textualität unkonventionell aus den Items sprachliches Wagnis und inhaltliches Wagnis zusammen. (DIPF/Orig.)In the project “Peer feedback within cooperative settings for text revision in German classes in primary schools” a rating system comprising 10 dimensions was developed to evaluate the quality of student story writing. The sample consisted of 132 texts written by 3rd grade students. First analyses show that the quality of student texts could be evaluated with an acceptable degree of correspondence among the raters. Secondly, the structure of the hypothesized model was tested by using a confirmatory factor analysis (CFA). These results indicated that the hypothesized model did not fit the data. Therefore the model was modified by eliminating three items. This modified model allows us to generate two valid factors (textuality – conventional/unconventional), which fit the model adequately. The factor textuality conventional comprises the items text coherency, textual implicitness, textual explicitness, vocabulary, the factor textuality unconventional comprises textual risk-taking, with regard to language and to content

Primary ChAdOx1 vaccination does not reactivate pre-existing, cross-reactive immunity

Currently available COVID-19 vaccines include inactivated virus, live attenuated virus, mRNA-based, viral vectored and adjuvanted protein-subunit-based vaccines. All of them contain the spike glycoprotein as the main immunogen and result in reduced disease severity upon SARS-CoV-2 infection. While we and others have shown that mRNA-based vaccination reactivates pre-existing, cross-reactive immunity, the effect of vector vaccines in this regard is unknown. Here, we studied cellular and humoral responses in heterologous adenovirus-vector-based ChAdOx1 nCOV-19 (AZ; Vaxzeria, AstraZeneca) and mRNA-based BNT162b2 (BNT; Comirnaty, BioNTech/Pfizer) vaccination and compared it to a homologous BNT vaccination regimen. AZ primary vaccination did not lead to measurable reactivation of cross-reactive cellular and humoral immunity compared to BNT primary vaccination. Moreover, humoral immunity induced by primary vaccination with AZ displayed differences in linear spike peptide epitope coverage and a lack of anti-S2 IgG antibodies. Contrary to primary AZ vaccination, secondary vaccination with BNT reactivated pre-existing, cross-reactive immunity, comparable to homologous primary and secondary mRNA vaccination. While induced anti-S1 IgG antibody titers were higher after heterologous vaccination, induced CD4(+) T cell responses were highest in homologous vaccinated. However, the overall TCR repertoire breadth was comparable between heterologous AZ-BNT-vaccinated and homologous BNT-BNT-vaccinated individuals, matching TCR repertoire breadths after SARS-CoV-2 infection, too. The reasons why AZ and BNT primary vaccination elicits different immune response patterns to essentially the same antigen, and the associated benefits and risks, need further investigation to inform vaccine and vaccination schedule development

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management