TY - JOUR A1 - Jones, Julia C. A1 - Fruciano, Carmelo A1 - Keller, Anja A1 - Schartl, Manfred A1 - Meyer, Axel T1 - Evolution of the elaborate male intromittent organ of Xiphophorus fishes JF - Ecology and Evolution N2 - Internally fertilizing animals show a remarkable diversity in male genital morphology that is associated with sexual selection, and these traits are thought to be evolving particularly rapidly. Male fish in some internally fertilizing species have “gonopodia,” highly modified anal fins that are putatively important for sexual selection. However, our understanding of the evolution of genital diversity remains incomplete. Contrary to the prediction that male genital traits evolve more rapidly than other traits, here we show that gonopodial traits and other nongonopodial traits exhibit similar evolutionary rates of trait change and also follow similar evolutionary models in an iconic genus of poeciliid fish (Xiphophorus spp.). Furthermore, we find that both mating and nonmating natural selection mechanisms are unlikely to be driving the diverse Xiphophorus gonopodial morphology. Putative holdfast features of the male genital organ do not appear to be influenced by water flow, a candidate selective force in aquatic habitats. Additionally, interspecific divergence in gonopodial morphology is not significantly higher between sympatric species, than between allopatric species, suggesting that male genitals have not undergone reproductive character displacement. Slower rates of evolution in gonopodial traits compared with a subset of putatively sexually selected nongenital traits suggest that different selection mechanisms may be acting on the different trait types. Further investigations of this elaborate trait are imperative to determine whether it is ultimately an important driver of speciation. KW - Male intromittent organ KW - reproductive character displacement KW - sexual selection KW - species diversification KW - Xiphophorus fish Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164956 VL - 6 IS - 20 ER - TY - JOUR A1 - Subramanian, Hariharan A1 - Döring, Frank A1 - Kollert, Sina A1 - Rukoyatkina, Natalia A1 - Sturm, Julia A1 - Gambaryan, Stepan A1 - Stellzig-Eisenhauer, Angelika A1 - Meyer-Marcotty, Philipp A1 - Eigenthaler, Martin A1 - Wischmeyer, Erhard T1 - PTH1R Mutants Found in Patients with Primary Failure of Tooth Eruption Disrupt G-Protein Signaling JF - PLoS One N2 - Aim Primary failure of tooth eruption (PFE) is causally linked to heterozygous mutations of the parathyroid hormone receptor (PTH1R) gene. The mutants described so far lead to exchange of amino acids or truncation of the protein that may result in structural changes of the expressed PTH1R. However, functional effects of these mutations have not been investigated yet. Materials and Methods In HEK293 cells, PTH1R wild type was co-transfected with selected PTH1R mutants identified in patients with PFE. The effects on activation of PTH-regulated intracellular signaling pathways were analyzed by ELISA and Western immunoblotting. Differential effects of wild type and mutated PTH1R on TRESK ion channel regulation were analyzed by electrophysiological recordings in Xenopus laevis oocytes. Results In HEK293 cells, activation of PTH1R wild type increases cAMP and in response activates cAMP-stimulated protein kinase as detected by phosphorylation of the vasodilator stimulated phosphoprotein (VASP). In contrast, the PTH1R mutants are functionally inactive and mutant PTH1R/Gly452Glu has a dominant negative effect on the signaling of PTH1R wild type. Confocal imaging revealed that wild type PTH1R is expressed on the cell surface, whereas PTH1R/Gly452Glu mutant is mostly retained inside the cell. Furthermore, in contrast to wild type PTH1R which substantially augmented K+ currents of TRESK channels, coupling of mutated PTH1R to TRESK channels was completely abolished. Conclusions PTH1R mutations affect intracellular PTH-regulated signaling in vitro. In patients with primary failure of tooth eruption defective signaling of PTH1R mutations is suggested to occur in dento-alveolar cells and thus may lead to impaired tooth movement. KW - phosphorylation KW - xenopus oocytes KW - calcium signaling KW - intracellular receptors KW - mutation KW - teeth KW - tooth eruption KW - transfection Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147967 VL - 11 IS - 11 ER - TY - THES A1 - Meyer, Julia T1 - Klinische Relevanz der Bestimmung von MMP-9 und TIMP-1 in BALF bei Lungenfibrose- und Sarkoidosepatienten T1 - Clinical relevance of the measurement of MMP-9 and TIMP-1 in BALF from patients with pulmonary fibrosis and sarcoidosis N2 - Konzentrationen von MMP-9 und TIMP-1 (mittels ELISA) waren in der BALF von Lungenfibrosepatienten am höchsten, gefolgt von Sarkoidose- und Kontrollpersonen. Eine Beteiligung an der Entstehung einer Lungenfibrose konnte dementsprechend sowohl für MMP-9, als auch für TIMP-1 bestätigt werden. Dies ist vereinbar mit der Pathogenese der Erkrankung. MMP-9 degradiert Basalmembranen, ein Mechanismus, der für die Proliferation von Fibroblasten-Foci von Bedeutung ist. Die Konzentration von MMP und TIMP korrelierte positiv mit der Anzahl neutrophiler Granulozyten sowie Lymphozyten in der BAL und negativ zu Alveolarmakrophagen. Es stellte sich keine Beziehung zwischen MMP-9 bzw. TIMP-1 und dem klinischen Ausmaß der Erkrankung, gemessen an den Lungenfunktionswerten, heraus. Die molare Ratio von Patienten im Follow-up korrelierte jedoch signifikant negativ mit deren Vitalkapazität nach zwei Jahren. Aufgrund dieser Ergebnisse kamen wir zu der Schlussfolgerung, dass eine höhere Ratio mit einer Verschlechterung der Lungenfunktion im Verlauf einhergehen könnte. N2 - Concentrations of MMP-9 and TIMP-1 (with ELISA) were highest in BALF of patients with pulmonary fibrosis, followed by patients with sarcoidosis and controlls. According to this, an involvement in the development of lung fibrosis could be confirmed for MMP and TIMP. This is compatible to the pathogenesis of the disease. MMP-9 degrades basalmembranes, a mechanism which is of importance for proliferation of fibroblast-foci. The concentration of MMP and TIMP correlated positively with the amount of neutrophil granulocytes and lymphocytes and negatively to alveolar macrophages. There was no correlation between MMP-9 respectively TIMP-1 and the clinical extent of the disease, measured by lung function. However, the molar ratio from patients in follow-up correlated significantly negatively with the vitalcapacity after two years. Because of these results we concluded that a higher ratio could go along with a decline in lung function. KW - Lungenfibrose KW - Sarkoidose KW - BALF KW - MMP KW - MMP-9 KW - TIMP KW - TIMP-1 KW - BALF KW - MMP KW - MMP-9 KW - TIMP KW - TIMP-1 Y1 - 2009 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-40984 ER - TY - JOUR A1 - Hebestreit, Helge A1 - Zeidler, Cornelia A1 - Schippers, Christopher A1 - de Zwaan, Martina A1 - Deckert, Jürgen A1 - Heuschmann, Peter A1 - Krauth, Christian A1 - Bullinger, Monika A1 - Berger, Alexandra A1 - Berneburg, Mark A1 - Brandstetter, Lilly A1 - Deibele, Anna A1 - Dieris-Hirche, Jan A1 - Graessner, Holm A1 - Gündel, Harald A1 - Herpertz, Stephan A1 - Heuft, Gereon A1 - Lapstich, Anne-Marie A1 - Lücke, Thomas A1 - Maisch, Tim A1 - Mundlos, Christine A1 - Petermann-Meyer, Andrea A1 - Müller, Susanne A1 - Ott, Stephan A1 - Pfister, Lisa A1 - Quitmann, Julia A1 - Romanos, Marcel A1 - Rutsch, Frank A1 - Schaubert, Kristina A1 - Schubert, Katharina A1 - Schulz, Jörg B. A1 - Schweiger, Susann A1 - Tüscher, Oliver A1 - Ungethüm, Kathrin A1 - Wagner, Thomas O. F. A1 - Haas, Kirsten T1 - Dual guidance structure for evaluation of patients with unclear diagnosis in centers for rare diseases (ZSE-DUO): study protocol for a controlled multi-center cohort study JF - Orphanet Journal of Rare Diseases N2 - Background In individuals suffering from a rare disease the diagnostic process and the confirmation of a final diagnosis often extends over many years. Factors contributing to delayed diagnosis include health care professionals' limited knowledge of rare diseases and frequent (co-)occurrence of mental disorders that may complicate and delay the diagnostic process. The ZSE-DUO study aims to assess the benefits of a combination of a physician focusing on somatic aspects with a mental health expert working side by side as a tandem in the diagnostic process. Study design This multi-center, prospective controlled study has a two-phase cohort design. Methods Two cohorts of 682 patients each are sequentially recruited from 11 university-based German Centers for Rare Diseases (CRD): the standard care cohort (control, somatic expertise only) and the innovative care cohort (experimental, combined somatic and mental health expertise). Individuals aged 12 years and older presenting with symptoms and signs which are not explained by current diagnoses will be included. Data will be collected prior to the first visit to the CRD’s outpatient clinic (T0), at the first visit (T1) and 12 months thereafter (T2). Outcomes Primary outcome is the percentage of patients with one or more confirmed diagnoses covering the symptomatic spectrum presented. Sample size is calculated to detect a 10 percent increase from 30% in standard care to 40% in the innovative dual expert cohort. Secondary outcomes are (a) time to diagnosis/diagnoses explaining the symptomatology; (b) proportion of patients successfully referred from CRD to standard care; (c) costs of diagnosis including incremental cost effectiveness ratios; (d) predictive value of screening instruments administered at T0 to identify patients with mental disorders; (e) patients’ quality of life and evaluation of care; and f) physicians’ satisfaction with the innovative care approach. Conclusions This is the first multi-center study to investigate the effects of a mental health specialist working in tandem with a somatic expert physician in CRDs. If this innovative approach proves successful, it will be made available on a larger scale nationally and promoted internationally. In the best case, ZSE-DUO can significantly shorten the time to diagnosis for a suspected rare disease. KW - rare diseases KW - multi‑center cohort study KW - dual guidance Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300440 VL - 17 IS - 1 ER - TY - JOUR A1 - Griebsch, Nora-Isabell A1 - Kern, Johanna A1 - Hansen, Jonas A1 - Rullmann, Michael A1 - Luthardt, Julia A1 - Helfmeyer, Stephanie A1 - Dekorsy, Franziska J. A1 - Soeder, Marvin A1 - Hankir, Mohammed K. A1 - Zientek, Franziska A1 - Becker, Georg-Alexander A1 - Patt, Marianne A1 - Meyer, Philipp M. A1 - Dietrich, Arne A1 - Blüher, Matthias A1 - Ding, Yu-Shin A1 - Hilbert, Anja A1 - Sabri, Osama A1 - Hesse, Swen T1 - Central serotonin/noradrenaline transporter availability and treatment success in patients with obesity JF - Brain Sciences N2 - Serotonin (5-hydroxytryptamine, 5-HT) as well as noradrenaline (NA) are key modulators of various fundamental brain functions including the control of appetite. While manipulations that alter brain serotoninergic signaling clearly affect body weight, studies implicating 5-HT transporters and NA transporters (5-HTT and NAT, respectively) as a main drug treatment target for human obesity have not been conclusive. The aim of this positron emission tomography (PET) study was to investigate how these central transporters are associated with changes of body weight after 6 months of dietary intervention or Roux-en-Y gastric bypass (RYGB) surgery in order to assess whether 5-HTT as well as NAT availability can predict weight loss and consequently treatment success. The study population consisted of two study cohorts using either the 5-HTT-selective radiotracer [\(^{11}\)C]DASB to measure 5-HTT availability or the NAT-selective radiotracer [\(^{11}\)C]MRB to assess NAT availability. Each group included non-obesity healthy participants, patients with severe obesity (body mass index, BMI, >35 kg/m\(^2\)) following a conservative dietary program (diet) and patients undergoing RYGB surgery within a 6-month follow-up. Overall, changes in BMI were not associated with changes of both 5-HTT and NAT availability, while 5-HTT availability in the dorsal raphe nucleus (DRN) prior to intervention was associated with substantial BMI reduction after RYGB surgery and inversely related with modest BMI reduction after diet. Taken together, the data of our study indicate that 5-HTT and NAT are involved in the pathomechanism of obesity and have the potential to serve as predictors of treatment outcomes. KW - obesity KW - serotonin KW - noradrenaline KW - serotonin transporter KW - noradrenaline transporter KW - Roux-en-Y gastric bypass surgery KW - body mass index (BMI; kg/m\(^2\)) KW - radiotracer KW - PET KW - PET imaging Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-290294 SN - 2076-3425 VL - 12 IS - 11 ER - TY - JOUR A1 - Schulmeyer, Carla E. A1 - Fasching, Peter A. A1 - Häberle, Lothar A1 - Meyer, Julia A1 - Schneider, Michael A1 - Wachter, David A1 - Ruebner, Matthias A1 - Pöschke, Patrik A1 - Beckmann, Matthias W. A1 - Hartmann, Arndt A1 - Erber, Ramona A1 - Gass, Paul T1 - Expression of the immunohistochemical markers CK5, CD117, and EGFR in molecular subtypes of breast cancer correlated with prognosis JF - Diagnostics N2 - Molecular-based subclassifications of breast cancer are important for identifying treatment options and stratifying the prognosis in breast cancer. This study aimed to assess the prognosis relative to disease-free survival (DFS) and overall survival (OS) in patients with triple-negative breast cancer (TNBC) and other subtypes, using a biomarker panel including cytokeratin 5 (CK5), cluster of differentiation 117 (CD117), and epidermal growth factor receptor (EGFR). This cohort–case study included histologically confirmed breast carcinomas as cohort arm. From a total of 894 patients, 572 patients with early breast cancer, sufficient clinical data, and archived tumor tissue were included. Using the immunohistochemical markers CK5, CD117, and EGFR, two subgroups were formed: one with all three biomarkers negative (TBN) and one with at least one of those three biomarkers positive (non-TBN). There were significant differences between the two biomarker subgroups (TBN versus non-TBN) in TNBC for DFS (p = 0.04) and OS (p = 0.02), with higher survival rates (DFS and OS) in the non-TBN subgroup. In this study, we found the non-TBN subgroup of TNBC lesions with at least one positive biomarker of CK5, CD117, and/or EGFR, to be associated with longer DFS and OS. KW - early breast cancer KW - therapy KW - prognosis KW - CK5 KW - CD117 KW - EGFR KW - triple-negative breast cancer Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304987 SN - 2075-4418 VL - 13 IS - 3 ER -