@article{SeefriedMuellerDeubertSchwarzetal.2010, author = {Seefried, Lothar and Mueller-Deubert, Sigrid and Schwarz, Thomas and Lind, Thomas and Mentrup, Birgit and Kober, Melanie and Docheva, Denitsa and Liedert, Astrid and Kassem, Moustapha and Ignatius, Anita and Schieker, Matthias and Claes, Lutz and Wilke, Winfried and Jakob, Franz and Ebert, Regina}, title = {A small scale cell culture system to analyze mechanobiology using reporter gene constructs and polyurethane dishes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68099}, year = {2010}, abstract = {Mechanical forces are translated into biochemical signals and contribute to cell differentiation and phenotype maintenance. Mesenchymal stem cells and their tissuespecific offspring, as osteoblasts and chondrocytes, cells of cardiovascular tissues and lung cells are sensitive to mechanical loading but molecules and mechanisms involved have to be unraveled. It is well established that cellular mechanotransduction is mediated e.g. by activation of the transcription factor SP1 and by kinase signaling cascades resulting in the activation of the AP1 complex. To investigate cellular mechanisms involved in mechanotransduction and to analyze substances, which modulate cellular mechanosensitivity reporter gene constructs, which can be transfected into cells of interest might be helpful. Suitable small-scale bioreactor systems and mechanosensitive reporter gene constructs are lacking. To analyze the molecular mechanisms of mechanotransduction and its crosstalk with biochemically induced signal transduction, AP1 and SP1 luciferase reporter gene constructs were cloned and transfected into various cell lines and primary cells. A newly developed bioreactor and small-scale 24-well polyurethane dishes were used to apply cyclic stretching to the transfected cells. 1 Hz cyclic stretching for 30 min in this system resulted in a significant stimulation of AP1 and SP1 mediated luciferase activity compared to unstimulated cells. In summary we describe a small-scale cell culture/bioreactor system capable of analyzing subcellular crosstalk mechanisms in mechanotransduction, mechanosensitivity of primary cells and of screening the activity of putative mechanosensitizers as new targets, e.g. for the treatment of bone loss caused by both disuse and signal transduction related alterations of mechanotransduction.}, subject = {Bioreaktor}, language = {en} } @article{MarenholzEsparzaGordilloRueschendorfetal.2015, author = {Marenholz, Ingo and Esparza-Gordillo, Jorge and R{\"u}schendorf, Franz and Bauerfeind, Anja and Strachan, David P. and Spycher, Ben D. and Baurecht, Hansj{\"o}rg and Magaritte-Jeannin, Patricia and S{\"a}{\"a}f, Annika and Kerkhof, Marjan and Ege, Markus and Baltic, Svetlana and Matheson, Melanie C. and Li, Jin and Michel, Sven and Ang, Wei Q. and McArdle, Wendy and Arnold, Andreas and Homuth, Georg and Demenais, Florence and Bouzigon, Emmanuelle and S{\"o}derh{\"a}ll, Cilla and Pershagen, G{\"o}ran and de Jongste, Johan C. and Postma, Dirkje S. and Braun-Fahrl{\"a}nder, Charlotte and Horak, Elisabeth and Ogorodova, Ludmila M. and Puzyrev, Valery P. and Bragina, Elena Yu and Hudson, Thomas J. and Morin, Charles and Duffy, David L. and Marks, Guy B. and Robertson, Colin F. and Montgomery, Grant W. and Musk, Bill and Thompson, Philip J. and Martin, Nicholas G. and James, Alan and Sleiman, Patrick and Toskala, Elina and Rodriguez, Elke and F{\"o}lster-Holst, Regina and Franke, Andre and Lieb, Wolfgang and Gieger, Christian and Heinzmann, Andrea and Rietschel, Ernst and Keil, Thomas and Cichon, Sven and N{\"o}then, Markus M. and Pennel, Craig E. and Sly, Peter D. and Schmidt, Carsten O. and Matanovic, Anja and Schneider, Valentin and Heinig, Matthias and H{\"u}bner, Norbert and Holt, Patrick G. and Lau, Susanne and Kabesch, Michael and Weidinger, Stefan and Hakonarson, Hakon and Ferreira, Manuel A. R. and Laprise, Catherine and Freidin, Maxim B. and Genuneit, Jon and Koppelman, Gerard H. and Mel{\´e}n, Erik and Dizier, Marie-H{\´e}l{\`e}ne and Henderson, A. John and Lee, Young Ae}, title = {Meta-analysis identifies seven susceptibility loci involved in the atopic march}, series = {Nature Communications}, volume = {6}, journal = {Nature Communications}, number = {8804}, doi = {10.1038/ncomms9804}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-139835}, year = {2015}, abstract = {Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P = 2.1 x 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P = 5.3 x 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.}, language = {en} } @article{KernAgarwalHuberetal.2014, author = {Kern, Selina and Agarwal, Shruti and Huber, Kilian and Gehring, Andre P. and Str{\"o}dke, Benjamin and Wirth, Christine C. and Br{\"u}gl, Thomas and Abodo, Liane Onambele and Dandekar, Thomas and Doerig, Christian and Fischer, Rainer and Tobin, Andrew B. and Alam, Mahmood M. and Bracher, Franz and Pradel, Gabriele}, title = {Inhibition of the SR Protein-Phosphorylating CLK Kinases of Plasmodium falciparum Impairs Blood Stage Replication and Malaria Transmission}, series = {PLOS ONE}, volume = {9}, journal = {PLOS ONE}, number = {9}, issn = {1932-6203}, doi = {10.1371/journal.pone.0105732}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115405}, pages = {e105732}, year = {2014}, abstract = {Cyclin-dependent kinase-like kinases (CLKs) are dual specificity protein kinases that phosphorylate Serine/Arginine-rich (SR) proteins involved in pre-mRNA processing. Four CLKs, termed PfCLK-1-4, can be identified in the human malaria parasite Plasmodium falciparum, which show homology with the yeast SR protein kinase Sky1p. The four PfCLKs are present in the nucleus and cytoplasm of the asexual blood stages and of gametocytes, sexual precursor cells crucial for malaria parasite transmission from humans to mosquitoes. We identified three plasmodial SR proteins, PfSRSF12, PfSFRS4 and PfSF-1, which are predominantly present in the nucleus of blood stage trophozoites, PfSRSF12 and PfSF-1 are further detectable in the nucleus of gametocytes. We found that recombinantly expressed SR proteins comprising the Arginine/Serine (RS)-rich domains were phosphorylated by the four PfCLKs in in vitro kinase assays, while a recombinant PfSF-1 peptide lacking the RS-rich domain was not phosphorylated. Since it was hitherto not possible to knock-out the pfclk genes by conventional gene disruption, we aimed at chemical knock-outs for phenotype analysis. We identified five human CLK inhibitors, belonging to the oxo-beta-carbolines and aminopyrimidines, as well as the antiseptic chlorhexidine as PfCLK-targeting compounds. The six inhibitors block P. falciparum blood stage replication in the low micromolar to nanomolar range by preventing the trophozoite-to-schizont transformation. In addition, the inhibitors impair gametocyte maturation and gametogenesis in in vitro assays. The combined data show that the four PfCLKs are involved in phosphorylation of SR proteins with essential functions for the blood and sexual stages of the malaria parasite, thus pointing to the kinases as promising targets for antimalarial and transmission blocking drugs.}, language = {en} } @article{DegenHovestadtMitesseretal.2017, author = {Degen, Tobias and Hovestadt, Thomas and Mitesser, Oliver and H{\"o}lker, Franz}, title = {Altered sex-specific mortality and female mating success: ecological effects and evolutionary responses}, series = {Ecosphere}, volume = {8}, journal = {Ecosphere}, number = {5}, doi = {10.1002/ecs2.1820}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170953}, pages = {e01820}, year = {2017}, abstract = {Theory predicts that males and females should often join the mating pool at different times (sexual dimorphism in timing of emergence [SDT]) as the degree of SDT affects female mating success. We utilize an analytical model to explore (1) how important SDT is for female mating success, (2) how mating success might change if either sex's mortality (abruptly) increases, and (3) to what degree evolutionary responses in SDT may be able to mitigate the consequences of such mortality increase. Increasing male pre-mating mortality has a non-linear effect on the fraction of females mated: The effect is initially weak, but at some critical level a further increase in male mortality has a stronger effect than a similar increase in female mortality. Such a change is expected to impose selection for reduced SDT. Increasing mortality during the mating season has always a stronger effect on female mating success if the mortality affects the sex that emerges first. This bias results from the fact that enhancing mortality of the earlier emerging sex reduces female-male encounter rates. However, an evolutionary response in SDT may effectively mitigate such consequences. Further, if considered independently for females and males, the predicted evolutionary response in SDT could be quite dissimilar. The difference between female and male evolutionary response in SDT leads to marked differences in the fraction of fertilized females under certain conditions. Our model may provide general guidelines for improving harvesting of populations, conservation management of rare species under altered environmental conditions, or maintaining long-term efficiency of pest-control measures.}, language = {en} } @article{JazbutyteStumpnerRedeletal.2012, author = {Jazbutyte, Virginija and Stumpner, Jan and Redel, Andreas and Lorenzen, Johan M. and Roewer, Norbert and Thum, Thomas and Kehl, Franz}, title = {Aromatase Inhibition Attenuates Desflurane-Induced Preconditioning against Acute Myocardial Infarction in Male Mouse Heart In Vivo}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151258}, pages = {e42032}, year = {2012}, abstract = {The volatile anesthetic desflurane (DES) effectively reduces cardiac infarct size following experimental ischemia/reperfusion injury in the mouse heart. We hypothesized that endogenous estrogens play a role as mediators of desflurane-induced preconditioning against myocardial infarction. In this study, we tested the hypothesis that desflurane effects local estrogen synthesis by modulating enzyme aromatase expression and activity in the mouse heart. Aromatase metabolizes testosterone to 17b- estradiol (E2) and thereby significantly contributes to local estrogen synthesis. We tested aromatase effects in acute myocardial infarction model in male mice. The animals were randomized and subjected to four groups which were pre-treated with the selective aromatase inhibitor anastrozole (A group) and DES alone (DES group) or in combination (A+DES group) for 15 minutes prior to surgical intervention whereas the control group received 0.9\% NaCl (CON group). All animals were subjected to 45 minutes ischemia following 180 minutes reperfusion. Anastrozole blocked DES induced preconditioning and increased infarct size compared to DES alone (37.94615.5\% vs. 17.163.62\%) without affecting area at risk and systemic hemodynamic parameters following ischemia/reperfusion. Protein localization studies revealed that aromatase was abundant in the murine cardiovascular system with the highest expression levels in endothelial and smooth muscle cells. Desflurane application at pharmacological concentrations efficiently upregulated aromatase expression in vivo and in vitro. We conclude that desflurane efficiently regulates aromatase expression and activity which might lead to increased local estrogen synthesis and thus preserve cellular integrity and reduce cardiac damage in an acute myocardial infarction model.}, language = {en} } @article{WeisSchoenVictoretal.2011, author = {Weis, Eva and Schoen, Holger and Victor, Anja and Spix, Claudia and Ludwig, Marco and Schneider-Raetzke, Brigitte and Kohlschmidt, Nicolai and Bartsch, Oliver and Gerhold-Ay, Aslihan and Boehm, Nils and Grus, Franz and Haaf, Thomas and Galetzka, Danuta}, title = {Reduced mRNA and Protein Expression of the Genomic Caretaker RAD9A in Primary Fibroblasts of Individuals with Childhood and Independent Second Cancer}, series = {PLoS ONE}, volume = {6}, journal = {PLoS ONE}, number = {10}, doi = {10.1371/journal.pone.0025750}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141838}, pages = {e25750}, year = {2011}, abstract = {Background: The etiology of secondary cancer in childhood cancer survivors is largely unclear. Exposure of normal somatic cells to radiation and/or chemotherapy can damage DNA and if not all DNA lesions are properly fixed, the mis-repair may lead to pathological consequences. It is plausible to assume that genetic differences, i.e. in the pathways responsible for cell cycle control and DNA repair, play a critical role in the development of secondary cancer. Methodology/Findings: To identify factors that may influence the susceptibility for second cancer formation, we recruited 20 individuals who survived a childhood malignancy and then developed a second cancer as well as 20 carefully matched control individuals with childhood malignancy but without a second cancer. By antibody microarrays, we screened primary fibroblasts of matched patients for differences in the amount of representative DNA repair-associated proteins. We found constitutively decreased levels of RAD9A and several other DNA repair proteins in two-cancer patients, compared to one-cancer patients. The RAD9A protein level increased in response to DNA damage, however to a lesser extent in the two-cancer patients. Quantification of mRNA expression by real-time RT PCR revealed lower RAD9A mRNA levels in both untreated and 1 Gy gamma-irradiated cells of two-cancer patients. Conclusions/Significance: Collectively, our results support the idea that modulation of RAD9A and other cell cycle arrest and DNA repair proteins contribute to the risk of developing a second malignancy in childhood cancer patients.}, language = {en} } @article{KlinkSauerKoerberetal.2015, author = {Klink, Thomas and Sauer, Johannes and K{\"o}rber, Norbert J and Grehn, Franz and Much, Martin M and Thederan, Luisa and Matlach, Juliane and Salgado, Josefina Parente}, title = {Quality of life following glaucoma surgery: canaloplasty versus trabeculectomy}, series = {Clinical Ophthalmology}, volume = {9}, journal = {Clinical Ophthalmology}, doi = {10.2147/OPTH.S72357}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149520}, pages = {7-16}, year = {2015}, abstract = {Purpose: To evaluate quality of life (QoL) with a new questionnaire after canaloplasty (CP) and trabeculectomy (TE). Patients and methods: We assessed outcomes of surgery, rate of revision surgeries, patients' mood, and influence of postoperative care on QoL, surgery interference with daily activities, and postsurgical complaints. Patients completed the QoL questionnaire 24 months after surgery. Results: Patients who underwent CP (n=175) were compared to TE patients (n=152). In the CP group, 57\% of patients expressed high satisfaction, while 41\% of patients in the TE group said they were highly satisfied. The satisfaction difference was statistically significant (P=0.034). Significantly fewer second surgeries were needed after CP (8\% CP versus 35\% TE, P<0.001). Patients were more positive in the CP group (54\% CP versus 37\% TE, P<0.009). Stress related to postoperative care was lower in the CP group compared to the TE group (14\% versus 46\%). Difficulties with activities of daily living, such as reading, were much lower or even nonexistent after CP, and complaints like eye burning or stinging were significantly lower in the CP group. Conclusions: Compared with TE, CP is associated with less QoL impairment and higher patient satisfaction after surgery. However, long-term data on intraocular pressure reduction after surgery are needed to confirm long-term patient satisfaction with this surgery.}, language = {en} } @article{DegenHovestadtMitesseretal.2015, author = {Degen, Tobias and Hovestadt, Thomas and Mitesser, Oliver and H{\"o}lker, Franz}, title = {High female survival promotes evolution of protogyny and xexual conflict}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {3}, doi = {10.1371/journal.pone.0118354}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143586}, pages = {e0118354}, year = {2015}, abstract = {Existing models explaining the evolution of sexual dimorphism in the timing of emergence (SDT) in Lepidoptera assume equal mortality rates for males and females. The limiting assumption of equal mortality rates has the consequence that these models are only able to explain the evolution of emergence of males before females, i.e. protandry-the more common temporal sequence of emergence in Lepidoptera. The models fail, however, in providing adaptive explanations for the evolution of protogyny, where females emerge before males, but protogyny is not rare in insects. The assumption of equal mortality rates seems too restrictive for many insects, such as butterflies. To investigate the influence of unequal mortality rates on the evolution of SDT, we present a generalised version of a previously published model where we relax this assumption. We find that longer life-expectancy of females compared to males can indeed favour the evolution of protogyny as a fitness enhancing strategy. Moreover, the encounter rate between females and males and the sex-ratio are two important factors that also influence the evolution of optimal SDT. If considered independently for females and males the predicted strategies can be shown to be evolutionarily stable (ESS). Under the assumption of equal mortality rates the difference between the females' and males' ESS remains typically very small. However, female and male ESS may be quite dissimilar if mortality rates are different. This creates the potential for an 'evolutionary conflict' between females and males. Bagworm moths (Lepidoptera: Psychidae) provide an exemplary case where life-history attributes are such that protogyny should indeed be the optimal emergence strategy from the males' and females' perspectives: (i) Female longevity is considerably larger than that of males, (ii) encounter rates between females and males are presumably low, and (iii) females mate only once. Protogyny is indeed the general mating strategy found in the bagworm family.}, language = {en} } @article{WeisSchoenVictoretal.2011, author = {Weis, Eva and Schoen, Holger and Victor, Anja and Spix, Claudia and Ludwig, Marco and Schneider-Raetzke, Brigitte and Kohlschmidt, Nicolai and Bartsch, Oliver and Gerhold-Ay, Aslihan and Boehm, Nils and Grus, Franz and Haaf, Thomas and Galetzka, Danuta}, title = {Reduced mRNA and Protein Expression of the Genomic Caretaker RAD9A in Primary Fibroblasts of Individuals with Childhood and Independent Second Cancer}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-74777}, year = {2011}, abstract = {Background: The etiology of secondary cancer in childhood cancer survivors is largely unclear. Exposure of normal somatic cells to radiation and/or chemotherapy can damage DNA and if not all DNA lesions are properly fixed, the mis-repair may lead to pathological consequences. It is plausible to assume that genetic differences, i.e. in the pathways responsible for cell cycle control and DNA repair, play a critical role in the development of secondary cancer. Methodology/Findings: To identify factors that may influence the susceptibility for second cancer formation, we recruited 20 individuals who survived a childhood malignancy and then developed a second cancer as well as 20 carefully matched control individuals with childhood malignancy but without a second cancer. By antibody microarrays, we screened primary fibroblasts of matched patients for differences in the amount of representative DNA repair-associated proteins. We found constitutively decreased levels of RAD9A and several other DNA repair proteins in two-cancer patients, compared to onecancer patients. The RAD9A protein level increased in response to DNA damage, however to a lesser extent in the twocancer patients. Quantification of mRNA expression by real-time RT PCR revealed lower RAD9A mRNA levels in both untreated and 1 Gy c-irradiated cells of two-cancer patients. Conclusions/Significance: Collectively, our results support the idea that modulation of RAD9A and other cell cycle arrest and DNA repair proteins contribute to the risk of developing a second malignancy in childhood cancer patients.}, subject = {Medizin}, language = {en} } @article{MatlachHoffmannFreibergetal.2012, author = {Matlach, Juliane and Hoffmann, Niels and Freiberg, Florentina J. and Grehn, Franz and Klink, Thomas}, title = {Comparative study of trabeculectomy using single sutures versus releasable sutures}, series = {Clinical ophthalmology}, volume = {6}, journal = {Clinical ophthalmology}, doi = {http://dx.doi.org/10.2147/OPTH.S32503}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-123715}, pages = {1019-1027}, year = {2012}, abstract = {BACKGROUND: The purpose of this study was to compare the outcomes of trabeculectomy using single sutures or releasable sutures. METHODS: This retrospective study analyzed the medical records of 61 patients who had undergone trabeculectomy using single sutures (n = 33, 54.1\%) or releasable sutures (n = 28, 45.9\%). The scleral flap was secured with a mean 3.9 (range 3-5) single sutures in 33 patients and with three releasable sutures in 28 patients. Primary outcomes were the success rate, based on intraocular pressure and medication usage, and the frequency of complications and post-surgical interventions. The criteria used to determine complete success were, first, intraocular pressure < 18 mmHg and, second, <=21 mmHg and >=20\% intraocular pressure reduction without glaucoma medication. RESULTS: All patients had an intraocular pressure <= 21 mmHg; 87.5\% in the single suture group and 92.6\% in the releasable suture group had an intraocular pressure < 18 mmHg at 24 months. There was a highly significant reduction in intraocular pressure to baseline values in both groups at the last visit. Applying the first criterion, complete success was achieved in 57.6\% of patients with single sutures and 71.4\% with releasable sutures, and based on the second criterion, 66.7\% and 71.4\%, respectively. No significant difference was found between the groups with regard to intraocular pressure, or success or complication rates. CONCLUSION: The results of trabeculectomy using single sutures or releasable sutures are equivalent. Therefore, the choice of suture technique should be based on individual patient requirements and surgeon experience.}, language = {en} } @article{VortkampFranzGessleretal.1992, author = {Vortkamp, Andrea and Franz, Thomas and Gessler, Manfred and Grzeschik, Karl-Heinz}, title = {Deletion of GLI3 supports the homology of the human Greig cephalopolysyndactyly syndrome (GCPS) and the mouse mutant extra toes (Xt)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-30166}, year = {1992}, abstract = {No abstract available}, language = {en} } @article{KlinkSauerKoerberetal.2014, author = {Klink, Thomas and Sauer, Johannes and K{\"o}rber, Norbert J. and Grehn, Franz and Much, Martin M. and Thederan, Luisa and Matlach, Juliane and Salgado, Josefina Parente}, title = {Quality of life following glaucoma surgery: canaloplasty versus trabeculectomy}, doi = {10.2147/OPTH.S72357}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-113596}, year = {2014}, abstract = {Purpose: To evaluate quality of life (QoL) with a new questionnaire after canaloplasty (CP) and trabeculectomy (TE). Patients and methods: We assessed outcomes of surgery, rate of revision surgeries, patients' mood, and influence of postoperative care on QoL, surgery interference with daily activities, and postsurgical complaints. Patients completed the QoL questionnaire 24 months after surgery. Results: Patients who underwent CP (n=175) were compared to TE patients (n=152). In the CP group, 57\% of patients expressed high satisfaction, while 41\% of patients in the TE group said they were highly satisfied. The satisfaction difference was statistically significant (P=0.034). Significantly fewer second surgeries were needed after CP (8\% CP versus 35\% TE, P<0.001). Patients were more positive in the CP group (54\% CP versus 37\% TE, P<0.009). Stress related to postoperative care was lower in the CP group compared to the TE group (14\% versus 46\%). Difficulties with activities of daily living, such as reading, were much lower or even nonexistent after CP, and complaints like eye burning or stinging were significantly lower in the CP group. Conclusions: Compared with TE, CP is associated with less QoL impairment and higher patient satisfaction after surgery. However, long-term data on intraocular pressure reduction after surgery are needed to confirm long-term patient satisfaction with this surgery.}, language = {en} } @article{FreibergMatlachGrehnetal.2013, author = {Freiberg, Florentina Joyce and Matlach, Juliane and Grehn, Franz and Karl, Sabine and Klink, Thomas}, title = {Postoperative subconjunctival bevacizumab injection as an adjunct to 5-fluorouracil in the management of scarring after trabeculectomy}, series = {Clinical Ophthalmology}, journal = {Clinical Ophthalmology}, doi = {10.2147/OPTH.S41750}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96546}, year = {2013}, abstract = {Purpose: Scarring after glaucoma filtering surgery remains the most frequent cause for bleb failure. The aim of this study was to assess if the postoperative injection of bevacizumab reduces the number of postoperative subconjunctival 5-fluorouracil (5-FU) injections. Further, the effect of bevacizumab as an adjunct to 5-FU on the intraocular pressure (IOP) outcome, bleb morphology, postoperative medications, and complications was evaluated. Methods: Glaucoma patients (N = 61) who underwent trabeculectomy with mitomycin C were analyzed retrospectively (follow-up period of 25 ± 19 months). Surgery was performed exclusively by one experienced glaucoma specialist using a standardized technique. Patients in group 1 received subconjunctival applications of 5-FU postoperatively. Patients in group 2 received 5-FU and subconjunctival injection of bevacizumab. Results: Group 1 had 6.4 ± 3.3 (0-15) (mean ± standard deviation and range, respectively) 5-FU injections. Group 2 had 4.0 ± 2.8 (0-12) (mean ± standard deviation and range, respectively) 5-FU injections. The added injection of bevacizumab significantly reduced the mean number of 5-FU injections by 2.4 ± 3.08 (P ≤ 0.005). There was no significantly lower IOP in group 2 when compared to group 1. A significant reduction in vascularization and in cork screw vessels could be found in both groups (P < 0.0001, 7 days to last 5-FU), yet there was no difference between the two groups at the last follow-up. Postoperative complications were significantly higher for both groups when more 5-FU injections were applied. (P = 0.008). No significant difference in best corrected visual acuity (P = 0.852) and visual field testing (P = 0.610) between preoperative to last follow-up could be found between the two groups. Conclusion: The postoperative injection of bevacizumab reduced the number of subconjunctival 5-FU injections significantly by 2.4 injections. A significant difference in postoperative IOP reduction, bleb morphology, and postoperative medication was not detected.}, language = {en} } @article{MatlachSloboddaGrehnetal.2012, author = {Matlach, Juliane and Slobodda, Joerg and Grehn, Franz and Klink, Thomas}, title = {Pars plana vitrectomy for malignant glaucoma in non-glaucomatous and in filtered glaucomatous eyes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-76375}, year = {2012}, abstract = {Purpose: To assess the outcomes of pars plana vitrectomy for the treatment of malignant glaucoma in patients with and without previous filtration surgery. Patients and methods: Data of 15 patients developing malignant glaucoma after trabeculectomy (60\%) or following ophthalmic interventions other than filtration surgery (40\%) were recorded retrospectively. Pars plana vitrectomy was performed in case of failed medical or laser treatment recreating the normal pathway of aqueous humor. The main outcome measures were the postoperative intraocular pressure (IOP), the frequency of complications, and success rate based on the following criteria: IOP reduction by \$20\% and to \#21 mmHg (definition one) or an IOP , 18 mmHg (definition two) with (qualified success) and without (complete success) glaucoma medication. Results: Vitrectomy reduced IOP from baseline in eyes with and without previous trabeculectomy during a median follow-up of 16.4 months (range 7 days to 58 months); although the majority of patients required glaucoma medication to reach desired IOP. The complete success rates were 11\% (both definitions) for patients with filtering blebs and none of the patients without previous trabeculectomy had complete success at the 12-month visit. Complications were few and included transient shallowing of the anterior chamber, choroidal detachment, corneal decompensation, filtering bleb failure, and need for further IOP-lowering procedures. Conclusion: Pars plana vitrectomy is equally effective for malignant glaucoma caused by trabeculectomy or interventions other than filtration surgery, although IOP-lowering medication is necessary in nearly all cases to maintain target IOP.}, subject = {Medizin}, language = {en} } @article{MatlachFreibergLeippietal.2013, author = {Matlach, Juliane and Freiberg, Florentina Joyce and Leippi, Swetlana and Grehn, Franz and Klink, Thomas}, title = {Comparison of phacotrabeculectomy versus phacocanaloplasty in the treatment of patients with concomitant cataract and glaucoma}, series = {BMC Ophthalmology}, journal = {BMC Ophthalmology}, doi = {10.1186/1471-2415-13-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-95948}, year = {2013}, abstract = {Background Cataract and glaucoma are both common comorbidities among older patients. Combining glaucoma surgery with minimal invasive phacoemulsification (phaco) is a considerable option to treat both conditions at the same time, although the combination with filtration surgery can produce a strong inflammatory response. Combined non-penetrating procedures like canaloplasty have shown to reduce intraocular pressure (IOP) comparable to trabeculectomy without the risk of serious bleb-related complications. The purpose of this retrospective study was to compare the outcomes of phacotrabeculectomy and phacocanaloplasty. Methods Thirty-nine eyes with concomitant cataract and glaucoma who underwent phacotrabeculectomy (n = 20; 51.3\%) or phacocanaloplasty (n = 19; 48.7\%) were included into this trial on reduction of IOP, use of medication, success rate, incidence of complications and postsurgical interventions. Complete success was defined as IOP reduction by 30\% or more and to 21 mmHg or less (definition 1a) or IOP to less than 18 mmHg (definition 2a) without glaucoma medication. Results Over a 12-month follow-up, baseline IOP significantly decreased from 30.0 ± 5.3 mmHg with a mean of 2.5 ± 1.2 glaucoma medications to 11.7 ± 3.5 mmHg with a mean of 0.2 ± 0.4 medications in eyes with phacotrabeculectomy (P < .0001). Eyes with phacocanaloplasty had a preoperative IOP of 28.3 ± 4.1 mmHg and were on 2.8 ± 1.1 IOP-lowering drugs. At 12 months, IOP significantly decreased to 12.6 ± 2.1 mmHg and less glaucoma medications were necessary (mean 1.0 ± 1.5 topical medications; P < .05). 15 patients (78.9\%) with phacotrabeculectomy and 9 patients (60.0\%) in the phacocanaloplasty group showed complete success according to definition 1 and 2 after 1 year (P = .276). Postsurgical complications were seen in 7 patients (36.8\%) of the phacocanaloplasty group which included intraoperative macroperforation of the trabeculo-Descemet membrane (5.3\%), hyphema (21.1\%) and bleb formation (10.5\%). Although more complications were observed in the phacotrabeculectomy group, no statistically significant difference was found. Conclusions Phacocanaloplasty offers a new alternative to phacotrabeculectomy for treatment of concomitant glaucoma and cataract, although phacotrabeculectomy yielded in better results in terms of IOP maintained without glaucoma medications.}, subject = {Augenkrankheit}, language = {en} } @article{SchwedhelmZdziebloAppeltMenzeletal.2019, author = {Schwedhelm, Ivo and Zdzieblo, Daniela and Appelt-Menzel, Antje and Berger, Constantin and Schmitz, Tobias and Schuldt, Bernhard and Franke, Andre and M{\"u}ller, Franz-Josef and Pless, Ole and Schwarz, Thomas and Wiedemann, Philipp and Walles, Heike and Hansmann, Jan}, title = {Automated real-time monitoring of human pluripotent stem cell aggregation in stirred tank reactors}, series = {Scientific Reports}, volume = {9}, journal = {Scientific Reports}, doi = {10.1038/s41598-019-48814-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202649}, pages = {12297}, year = {2019}, abstract = {The culture of human induced pluripotent stem cells (hiPSCs) at large scale becomes feasible with the aid of scalable suspension setups in continuously stirred tank reactors (CSTRs). Innovative monitoring options and emerging automated process control strategies allow for the necessary highly defined culture conditions. Next to standard process characteristics such as oxygen consumption, pH, and metabolite turnover, a reproducible and steady formation of hiPSC aggregates is vital for process scalability. In this regard, we developed a hiPSC-specific suspension culture unit consisting of a fully monitored CSTR system integrated into a custom-designed and fully automated incubator. As a step towards cost-effective hiPSC suspension culture and to pave the way for flexibility at a large scale, we constructed and utilized tailored miniature CSTRs that are largely made from three-dimensional (3D) printed polylactic acid (PLA) filament, which is a low-cost material used in fused deposition modelling. Further, the monitoring tool for hiPSC suspension cultures utilizes in situ microscopic imaging to visualize hiPSC aggregation in real-time to a statistically significant degree while omitting the need for time-intensive sampling. Suitability of our culture unit, especially concerning the developed hiPSC-specific CSTR system, was proven by demonstrating pluripotency of CSTR-cultured hiPSCs at RNA (including PluriTest) and protein level.}, language = {en} } @article{DollKolbSchnappetal.2020, author = {Doll, Julia and Kolb, Susanne and Schnapp, Linda and Rad, Aboulfazl and R{\"u}schendorf, Franz and Khan, Imran and Adli, Abolfazl and Hasanzadeh, Atefeh and Liedtke, Daniel and Knaup, Sabine and Hofrichter, Michaela AH and M{\"u}ller, Tobias and Dittrich, Marcus and Kong, Il-Keun and Kim, Hyung-Goo and Haaf, Thomas and Vona, Barbara}, title = {Novel loss-of-function variants in CDC14A are associated with recessive sensorineural hearing loss in Iranian and Pakistani patients}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {1}, issn = {1422-0067}, doi = {10.3390/ijms21010311}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285142}, year = {2020}, abstract = {CDC14A encodes the Cell Division Cycle 14A protein and has been associated with autosomal recessive non-syndromic hearing loss (DFNB32), as well as hearing impairment and infertile male syndrome (HIIMS) since 2016. To date, only nine variants have been associated in patients whose initial symptoms included moderate-to-profound hearing impairment. Exome analysis of Iranian and Pakistani probands who both showed bilateral, sensorineural hearing loss revealed a novel splice site variant (c.1421+2T>C, p.?) that disrupts the splice donor site and a novel frameshift variant (c.1041dup, p.Ser348Glnfs*2) in the gene CDC14A, respectively. To evaluate the pathogenicity of both loss-of-function variants, we analyzed the effects of both variants on the RNA-level. The splice variant was characterized using a minigene assay. Altered expression levels due to the c.1041dup variant were assessed using RT-qPCR. In summary, cDNA analysis confirmed that the c.1421+2T>C variant activates a cryptic splice site, resulting in a truncated transcript (c.1414_1421del, p.Val472Leufs*20) and the c.1041dup variant results in a defective transcript that is likely degraded by nonsense-mediated mRNA decay. The present study functionally characterizes two variants and provides further confirmatory evidence that CDC14A is associated with a rare form of hereditary hearing loss.}, language = {en} } @article{KaltdorfBreitenbachKarletal.2023, author = {Kaltdorf, Martin and Breitenbach, Tim and Karl, Stefan and Fuchs, Maximilian and Kessie, David Komla and Psota, Eric and Prelog, Martina and Sarukhanyan, Edita and Ebert, Regina and Jakob, Franz and Dandekar, Gudrun and Naseem, Muhammad and Liang, Chunguang and Dandekar, Thomas}, title = {Software JimenaE allows efficient dynamic simulations of Boolean networks, centrality and system state analysis}, series = {Scientific Reports}, volume = {13}, journal = {Scientific Reports}, doi = {10.1038/s41598-022-27098-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313303}, year = {2023}, abstract = {The signal modelling framework JimenaE simulates dynamically Boolean networks. In contrast to SQUAD, there is systematic and not just heuristic calculation of all system states. These specific features are not present in CellNetAnalyzer and BoolNet. JimenaE is an expert extension of Jimena, with new optimized code, network conversion into different formats, rapid convergence both for system state calculation as well as for all three network centralities. It allows higher accuracy in determining network states and allows to dissect networks and identification of network control type and amount for each protein with high accuracy. Biological examples demonstrate this: (i) High plasticity of mesenchymal stromal cells for differentiation into chondrocytes, osteoblasts and adipocytes and differentiation-specific network control focusses on wnt-, TGF-beta and PPAR-gamma signaling. JimenaE allows to study individual proteins, removal or adding interactions (or autocrine loops) and accurately quantifies effects as well as number of system states. (ii) Dynamical modelling of cell-cell interactions of plant Arapidopsis thaliana against Pseudomonas syringae DC3000: We analyze for the first time the pathogen perspective and its interaction with the host. We next provide a detailed analysis on how plant hormonal regulation stimulates specific proteins and who and which protein has which type and amount of network control including a detailed heatmap of the A.thaliana response distinguishing between two states of the immune response. (iii) In an immune response network of dendritic cells confronted with Aspergillus fumigatus, JimenaE calculates now accurately the specific values for centralities and protein-specific network control including chemokine and pattern recognition receptors.}, language = {en} } @article{SadovnickTraboulseeBernalesetal.2016, author = {Sadovnick, A. Dessa and Traboulsee, Anthony L. and Bernales, Cecily Q. and Ross, Jay P. and Forwell, Amanda L. and Yee, Irene M. and Guillot-Noel, Lena and Fontaine, Bertrand and Cournu-Rebeix, Isabelle and Alcina, Antonio and Fedetz, Maria and Izquierdo, Guillermo and Matesanz, Fuencisla and Hilven, Kelly and Dubois, B{\´e}n{\´e}dicte and Goris, An and Astobiza, Ianire and Alloza, Iraide and Antig{\"u}edad, Alfredo and Vandenbroeck, Koen and Akkad, Denis A. and Aktas, Orhan and Blaschke, Paul and Buttmann, Mathias and Chan, Andrew and Epplen, Joerg T. and Gerdes, Lisa-Ann and Kroner, Antje and Kubisch, Christian and K{\"u}mpfel, Tania and Lohse, Peter and Rieckmann, Peter and Zettl, Uwe K. and Zipp, Frauke and Bertram, Lars and Lill, Christina M. and Fernandez, Oscar and Urbaneja, Patricia and Leyva, Laura and Alvarez-Cerme{\~n}o, Jose Carlos and Arroyo, Rafael and Garagorri, Aroa M. and Garc{\´i}a-Mart{\´i}nez, Angel and Villar, Luisa M. and Urcelay, Elena and Malhotra, Sunny and Montalban, Xavier and Comabella, Manuel and Berger, Thomas and Fazekas, Franz and Reindl, Markus and Schmied, Mascha C. and Zimprich, Alexander and Vilari{\~n}o-G{\"u}ell, Carles}, title = {Analysis of Plasminogen Genetic Variants in Multiple Sclerosis Patients}, series = {G3: Genes Genomes Genetics}, volume = {6}, journal = {G3: Genes Genomes Genetics}, number = {7}, doi = {10.1534/g3.116.030841}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165405}, pages = {2073-2079}, year = {2016}, abstract = {Multiple sclerosis (MS) is a prevalent neurological disease of complex etiology. Here, we describe the characterization of a multi-incident MS family that nominated a rare missense variant (p.G420D) in plasminogen (PLG) as a putative genetic risk factor for MS. Genotyping of PLG p.G420D (rs139071351) in 2160 MS patients, and 886 controls from Canada, identified 10 additional probands, two sporadic patients and one control with the variant. Segregation in families harboring the rs139071351 variant, identified p.G420D in 26 out of 30 family members diagnosed with MS, 14 unaffected parents, and 12 out of 30 family members not diagnosed with disease. Despite considerably reduced penetrance, linkage analysis supports cosegregation of PLG p.G420D and disease. Genotyping of PLG p.G420D in 14446 patients, and 8797 controls from Canada, France, Spain, Germany, Belgium, and Austria failed to identify significant association with disease (P = 0.117), despite an overall higher prevalence in patients (OR = 1.32; 95\% CI = 0.93-1.87). To assess whether additional rare variants have an effect on MS risk, we sequenced PLG in 293 probands, and genotyped all rare variants in cases and controls. This analysis identified nine rare missense variants, and although three of them were exclusively observed in MS patients, segregation does not support pathogenicity. PLG is a plausible biological candidate for MS owing to its involvement in immune system response, blood-brain barrier permeability, and myelin degradation. Moreover, components of its activation cascade have been shown to present increased activity or expression in MS patients compared to controls; further studies are needed to clarify whether PLG is involved in MS susceptibility.}, language = {en} } @article{DienemannFujiiOrlandietal.2016, author = {Dienemann, Thomas and Fujii, Naohiko and Orlandi, Paula and Nessel, Lisa and Furth, Susan L. and Hoy, Wendy E. and Matsuo, Seiichi and Mayer, Gert and Methven, Shona and Schaefer, Franz and Schaeffner, Elke S. and Sol{\´a}, Laura and Stengel, B{\´e}n{\´e}dicte and Wanner, Christoph and Zhang, Luxia and Levin, Adeera and Eckardt, Kai-Uwe and Feldman, Harold I.}, title = {International Network of Chronic Kidney Disease cohort studies (iNET-CKD): a global network of chronic kidney disease cohorts}, series = {BMC Nephrology}, volume = {17}, journal = {BMC Nephrology}, doi = {10.1186/s12882-016-0335-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164604}, pages = {121}, year = {2016}, abstract = {Background Chronic kidney disease (CKD) is a global health burden, yet it is still underrepresented within public health agendas in many countries. Studies focusing on the natural history of CKD are challenging to design and conduct, because of the long time-course of disease progression, a wide variation in etiologies, and a large amount of clinical variability among individuals with CKD. With the difference in health-related behaviors, healthcare delivery, genetics, and environmental exposures, this variability is greater across countries than within one locale and may not be captured effectively in a single study. Methods Studies were invited to join the network. Prerequisites for membership included: 1) observational designs with a priori hypotheses and defined study objectives, patient-level information, prospective data acquisition and collection of bio-samples, all focused on predialysis CKD patients; 2) target sample sizes of 1,000 patients for adult cohorts and 300 for pediatric cohorts; and 3) minimum follow-up of three years. Participating studies were surveyed regarding design, data, and biosample resources. Results Twelve prospective cohort studies and two registries covering 21 countries were included. Participants age ranges from >2 to >70 years at inclusion, CKD severity ranges from stage 2 to stage 5. Patient data and biosamples (not available in the registry studies) are measured yearly or biennially. Many studies included multiple ethnicities; cohort size ranges from 400 to more than 13,000 participants. Studies' areas of emphasis all include but are not limited to renal outcomes, such as progression to ESRD and death. Conclusions iNET-CKD (International Network of CKD cohort studies) was established, to promote collaborative research, foster exchange of expertise, and create opportunities for research training. Participating studies have many commonalities that will facilitate comparative research; however, we also observed substantial differences. The diversity we observed across studies within this network will be able to be leveraged to identify genetic, behavioral, and health services factors associated with the course of CKD. With an emerging infrastructure to facilitate interactions among the investigators of iNET-CKD and a broadly defined research agenda, we are confident that there will be great opportunity for productive collaborative investigations involving cohorts of individuals with CKD.}, language = {en} } @article{DollVonaSchnappetal.2020, author = {Doll, Julia and Vona, Barbara and Schnapp, Linda and R{\"u}schendorf, Franz and Khan, Imran and Khan, Saadullah and Muhammad, Noor and Alam Khan, Sher and Nawaz, Hamed and Khan, Ajmal and Ahmad, Naseer and Kolb, Susanne M. and K{\"u}hlewein, Laura and Labonne, Jonathan D. J. and Layman, Lawrence C. and Hofrichter, Michaela A. H. and R{\"o}der, Tabea and Dittrich, Marcus and M{\"u}ller, Tobias and Graves, Tyler D. and Kong, Il-Keun and Nanda, Indrajit and Kim, Hyung-Goo and Haaf, Thomas}, title = {Genetic Spectrum of Syndromic and Non-Syndromic Hearing Loss in Pakistani Families}, series = {Genes}, volume = {11}, journal = {Genes}, number = {11}, issn = {2073-4425}, doi = {10.3390/genes11111329}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219293}, year = {2020}, abstract = {The current molecular genetic diagnostic rates for hereditary hearing loss (HL) vary considerably according to the population background. Pakistan and other countries with high rates of consanguineous marriages have served as a unique resource for studying rare and novel forms of recessive HL. A combined exome sequencing, bioinformatics analysis, and gene mapping approach for 21 consanguineous Pakistani families revealed 13 pathogenic or likely pathogenic variants in the genes GJB2, MYO7A, FGF3, CDC14A, SLITRK6, CDH23, and MYO15A, with an overall resolve rate of 61.9\%. GJB2 and MYO7A were the most frequently involved genes in this cohort. All the identified variants were either homozygous or compound heterozygous, with two of them not previously described in the literature (15.4\%). Overall, seven missense variants (53.8\%), three nonsense variants (23.1\%), two frameshift variants (15.4\%), and one splice-site variant (7.7\%) were observed. Syndromic HL was identified in five (23.8\%) of the 21 families studied. This study reflects the extreme genetic heterogeneity observed in HL and expands the spectrum of variants in deafness-associated genes.}, language = {en} } @article{MatlachDhillonHainetal.2015, author = {Matlach, Juliane and Dhillon, Christine and Hain, Johannes and Schlunck, G{\"u}nther and Grehn, Franz and Klink, Thomas}, title = {Trabeculectomy versus canaloplasty (TVC study) in the treatment of patients with open-angle glaucoma: a prospective randomized clinical trial}, series = {Acta Ophthalmologica}, volume = {93}, journal = {Acta Ophthalmologica}, doi = {10.1111/aos.12722}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149263}, pages = {753-761}, year = {2015}, abstract = {Purpose: To compare the outcomes of canaloplasty and trabeculectomy in open-angle glaucoma. Methods: This prospective, randomized clinical trial included 62 patients who randomly received trabeculectomy (n = 32) or canaloplasty (n = 30) and were followed up prospectively for 2 years. Primary endpoint was complete (without medication) and qualified success (with or without medication) defined as an intraocular pressure (IOP) of ≤18 mmHg (definition 1) or IOP ≤21 mmHg and ≥20\% IOP reduction (definition 2), IOP ≥5 mmHg, no vision loss and no further glaucoma surgery. Secondary endpoints were the absolute IOP reduction, visual acuity, medication, complications and second surgeries. Results: Surgical treatment significantly reduced IOP in both groups (p < 0.001). Complete success was achieved in 74.2\% and 39.1\% (definition 1, p = 0.01), and 67.7\% and 39.1\% (definition 2, p = 0.04) after 2 years in the trabeculectomy and canaloplasty group, respectively. Mean absolute IOP reduction was 10.8 ± 6.9 mmHg in the trabeculectomy and 9.3 ± 5.7 mmHg in the canaloplasty group after 2 years (p = 0.47). Mean IOP was 11.5 ± 3.4 mmHg in the trabeculectomy and 14.4 ± 4.2 mmHg in the canaloplasty group after 2 years. Following trabeculectomy, complications were more frequent including hypotony (37.5\%), choroidal detachment (12.5\%) and elevated IOP (25.0\%). Conclusions: Trabeculectomy is associated with a stronger IOP reduction and less need for medication at the cost of a higher rate of complications. If target pressure is attainable by moderate IOP reduction, canaloplasty may be considered for its relative ease of postoperative care and lack of complications.}, language = {en} } @article{VonaMazaheriLinetal.2021, author = {Vona, Barbara and Mazaheri, Neda and Lin, Sheng-Jia and Dunbar, Lucy A. and Maroofian, Reza and Azaiez, Hela and Booth, Kevin T. and Vitry, Sandrine and Rad, Aboulfazl and R{\"u}schendorf, Franz and Varshney, Pratishtha and Fowler, Ben and Beetz, Christian and Alagramam, Kumar N. and Murphy, David and Shariati, Gholamreza and Sedaghat, Alireza and Houlden, Henry and Petree, Cassidy and VijayKumar, Shruthi and Smith, Richard J. H. and Haaf, Thomas and El-Amraoui, Aziz and Bowl, Michael R. and Varshney, Gaurav K. and Galehdari, Hamid}, title = {A biallelic variant in CLRN2 causes non-syndromic hearing loss in humans}, series = {Human Genetics}, volume = {140}, journal = {Human Genetics}, number = {6}, issn = {1432-1203}, doi = {10.1007/s00439-020-02254-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267740}, pages = {915-931}, year = {2021}, abstract = {Deafness, the most frequent sensory deficit in humans, is extremely heterogeneous with hundreds of genes involved. Clinical and genetic analyses of an extended consanguineous family with pre-lingual, moderate-to-profound autosomal recessive sensorineural hearing loss, allowed us to identify CLRN2, encoding a tetraspan protein, as a new deafness gene. Homozygosity mapping followed by exome sequencing identified a 14.96 Mb locus on chromosome 4p15.32p15.1 containing a likely pathogenic missense variant in CLRN2 (c.494C > A, NM_001079827.2) segregating with the disease. Using in vitro RNA splicing analysis, we show that the CLRN2 c.494C > A variant leads to two events: (1) the substitution of a highly conserved threonine (uncharged amino acid) to lysine (charged amino acid) at position 165, p.(Thr165Lys), and (2) aberrant splicing, with the retention of intron 2 resulting in a stop codon after 26 additional amino acids, p.(Gly146Lysfs*26). Expression studies and phenotyping of newly produced zebrafish and mouse models deficient for clarin 2 further confirm that clarin 2, expressed in the inner ear hair cells, is essential for normal organization and maintenance of the auditory hair bundles, and for hearing function. Together, our findings identify CLRN2 as a new deafness gene, which will impact future diagnosis and treatment for deaf patients.}, language = {en} } @article{FiedlerHeyneBogner2022, author = {Fiedler, Sonja T. and Heyne, Thomas and Bogner, Franz X.}, title = {Closing the gap: potentials of ESE distance teaching}, series = {Sustainability}, volume = {14}, journal = {Sustainability}, number = {14}, issn = {2071-1050}, doi = {10.3390/su14148330}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281893}, year = {2022}, abstract = {Environmental and sustainability education (ESE) traditionally relies on green teaching environments and active participation. Thus, during the lockdown phase, a gap between curricular goals and learning outcomes appeared. This study investigates the impact of ESE distance teaching on 288 Bavarian fifth-graders and learning factors that could bridge this gap. The influence of digital preferences on learning progress is examined and compared with the influence of fascination levels. A negative correlation between spending time outside in nature and spending time inside in front of a digital device is expected. A control group completed a learning unit about biological topics such as plant identification and environmental factors, as well as ESE topics such as characteristics of sustainable agriculture, at an out-of-school ESE center. The experimental group completed the same learning unit in distance teaching. Fascination with Biology (FBio) and Digital Nativity Assessment Scale (DNAS) were applied in addition to a customized knowledge test. Both values seem to have a positive impact on learning outcomes. There were no significant differences between the control and experimental group. Surprisingly, Fascination and Digital Nativity show a low, if not negligible, relationship. Implications for digital ESE, especially between outdoor learning centers and schools, are discussed.}, language = {en} } @article{FiedlerHeyneBogner2021, author = {Fiedler, Sonja T. and Heyne, Thomas and Bogner, Franz X.}, title = {COVID-19 and lockdown schooling: how digital learning environments influence semantic structures and sustainability knowledge}, series = {Discover Sustainability}, volume = {2}, journal = {Discover Sustainability}, doi = {10.1007/s43621-021-00041-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261572}, year = {2021}, abstract = {Promoting sustainable lifestyles through Education for Sustainable Development (ESD) is part of the UN's Agenda 2030. Earlier empirical studies proved direct interactions with and in natural environments to be effective ESD methods. Pandemic-related lockdowns rendered such courses nearly impossible, which raised concerns about achieving the Sustainable Development Goals (SDGs) in general. To evaluate what young learners know about the concept sustainability so far and how it can be taught effectively online, we designed an online learning module tackling sustainability issues and compared it with data from an on-site intervention module for Bavarian 5th graders (~ 10 years old). Cognitive learning as well as attitudinal preferences of 288 learners were monitored in a pretest-posttest design. The learning module comprised two sections: One about botany, plant characteristics, and plant families; the other about the advantages and disadvantages of traditional as well as sustainable farming methods. The customized cognitive test and semantic differentials for sustainability and environmental protection produced three major findings: (1) A digital learning environment successfully and significantly increased sustainability knowledge (2) Learners clearly distinguished the concepts Sustainability and Environmental Protection (3) There is no direct correlation between semantic differential scores and learning outcome.}, language = {en} } @article{StormsJakharMitesseretal.2022, author = {Storms, Mona and Jakhar, Aryan and Mitesser, Oliver and Jechow, Andreas and H{\"o}lker, Franz and Degen, Tobias and Hovestadt, Thomas and Degen, Jacqueline}, title = {The rising moon promotes mate finding in moths}, series = {Communications Biology}, volume = {5}, journal = {Communications Biology}, doi = {10.1038/s42003-022-03331-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301365}, year = {2022}, abstract = {To counteract insect decline, it is essential to understand the underlying causes, especially for key pollinators such as nocturnal moths whose ability to orientate can easily be influenced by ambient light conditions. These comprise natural light sources as well as artificial light, but their specific relevance for moth orientation is still unknown. We investigated the influence of moonlight on the reproductive behavior of privet hawkmoths (Sphinx ligustri) at a relatively dark site where the Milky Way was visible while the horizon was illuminated by distant light sources and skyglow. We show that male moths use the moon for orientation and reach females significantly faster with increasing moon elevation. Furthermore, the choice of flight direction depended on the cardinal position of the moon but not on the illumination of the horizon caused by artificial light, indicating that the moon plays a key role in the orientation of male moths.}, language = {en} }