Ma L.,Salk Institute for Biological Studies |
Quigley I.,Salk Institute for Biological Studies |
Omran H.,University Hospital Muenster |
Kintner C.,Salk Institute for Biological Studies
Genes and Development | Year: 2014
Multiciliate cells employ hundreds of motile cilia to produce fluid flow, which they nucleate and extend by first assembling hundreds of centrioles. In most cells, entry into the cell cycle allows centrioles to undergo a single round of duplication, but in differentiating multiciliate cells, massive centriole assembly occurs in G0 by a process initiated by a small coiled-coil protein, Multicilin. Here we show that Multicilin acts by forming a ternary complex with E2f4 or E2f5 and Dp1 that binds and activates most of the genes required for centriole biogenesis, while other cell cycle genes remain off. This complex also promotes the deuterosome pathway of centriole biogenesis by activating the expression of deup1 but not its paralog, cep63. Finally, we show that this complex is disabled by mutations in human Multicilin that cause a severe congenital mucociliary clearance disorder due to reduced generation of multiple cilia. By coopting the E2f regulation of cell cycle genes, Multicilin drives massive centriole assembly in epithelial progenitors in a manner required for multiciliate cell differentiation. © 2014 Ma et al.
Troppmann B.,University Hospital Muenster |
Kleinau G.,Charite Universittsmedizin Berlin |
Krause G.,Leibniz Institute for Molecular Pharmacology |
Gromoll J.,University Hospital Muenster
Human Reproduction Update | Year: 2013
background: In recent years it became evident that several types of the luteinizing hormone/choriogonadotrophin receptor (LHCGR) exist. In addition to the classical receptor type known in rodents, an LHCGR type containing an additional exon is present in primates and humans. This specific exon 6A introduces a hitherto unknown regulatory pathway of the LHCGR at the transcriptional level which can lead to the expression of an alternative protein covering the extracellular part only. Furthermore, an LHCGR type lacking exon 10 at the mRNA and protein levels has been described in the New World primate lineage, giving rise to an additional receptor type in which amino acids of the extracellular hinge region connecting the leucine-rich repeat domain and transmembrane domain are missing. methods: Topic-related information was retrieved by systematic searches using Medline/PubMed. Structural homology models were retrieved from a glycoprotein hormone receptors web application and from recent publications. results: In a novel approach, we combine functional aspects with three-dimensional properties of the LHCGR and the different receptor types to deduce causative relationships between these two parameters. On this basis, the physiological impact and patho-physiological consequences of the different LHCGR types are inferred. conclusions: The complex system of differentLHCGRtypes and two corresponding hormones (LH andCG)represents a major challenge for future studies on selective hormone binding, signal transduction and receptor regulation. The presence of these naturally occurring LHCGR types requires re-examining of our present view on receptor function, experimental set-ups and data interpretation, but also offers new clinical approaches to interfere with LH/CG action in humans. ©The Author 2013. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
Lotts T.,University Hospital Muenster |
Stander S.,University Hospital Muenster
JDDG - Journal of the German Society of Dermatology | Year: 2014
Pruritus is an unpleasant sensation of the skin, which triggers a desire to scratch or rub. The chronic form (≥6 weeks' duration) often occurs as a side effect of many diseases and is usually accompanied by a high loss in quality of life for patients, especially in cases in which the symptom is chronic without adequate treatment options. In recent years, the situation improved continuously, guidelines for chronic pruritus have been defined and standard medications have been proposed. For many reasons, there are still patients who are unable to obtain relief. New therapeutic approaches are therefore urgently needed. Blocking the neuropeptide substance P is a promising strategy; substance P mediates clinically relevant pro-inflammatory effects by binding to the neurokinin 1 receptor (NK-1R). This led us to hypothesize that NK-1R antagonists are promising therapeutic options for chronic pruritus. Several international case series have meanwhile proven the antipruritic effect of the NK-1R antagonist aprepitant for various forms of chronic pruritus. Initiation of clinical trials with new NK-1R-antagonists as a new therapeutic option continues this trend. © 2014 Deutsche Dermatologische Gesellschaft (DDG).
Bosch K.,University Hospital Muenster |
Rosenbaum D.,University Hospital Muenster
Gait and Posture | Year: 2010
Children under 10 years of age are less efficient than adults regarding their dynamic balance control . The development of the somatosensory system is necessary for the control of posture and balance. The foot, as the final link between body and ground, transfers internal forces during gait. The coordination of force transfer needs to be balanced between both feet thus leading to a potential asymmetry of foot loading. The magnitude of asymmetry in infants' gait has been previously studied. However, the individual development and improvement of gait symmetry should also be considered. Therefore, the aim of this study was to retrospectively evaluate the longitudinal development of foot loading symmetries from the onset of independent walking. Sixty-two healthy infants were followed over the course of 4 years by means of plantar pressure distribution measurements (mean age of 15 months at study start and 63 months at the end). The subjects attended a total of nine measurements scheduled every 6 months. Foot loading data was recorded during walking with the emed® pressure platform to evaluate contact area, peak pressure, force-time integral, relative maximum force and contact time. An absolute symmetry index was calculated for all parameters. Furthermore, the infants' data were compared to the data of 26 healthy adults. The adults were measured once and the data acquisition followed exactly the same procedures as the infants' data. In conclusion, foot loading is asymmetric with the onset of independent walking and shows improved symmetry with increasing age dependent on the foot loading parameters. © 2010 Elsevier B.V.
Mennigen R.,University Hospital Muenster |
Senninger N.,University Hospital Muenster |
Laukoetter M.G.,University Hospital Muenster
World Journal of Gastroenterology | Year: 2014
Endoscopic management of leakages and perforations of the upper gastrointestinal tract has gained great importance as it avoids the morbidity and mortality of surgical intervention. In the past years, covered selfexpanding metal stents were the mainstay of endoscopic therapy. However, two new techniques are now available that enlarge the possibilities of defect closure: endoscopic vacuum therapy (EVT), and over-the-scope clip (OTSC). EVT is performed by mounting a polyurethane sponge on a gastric tube and placing it into the leakage. Continuous suction is applied via the tube resulting in effective drainage of the cavity and the induction of wound healing, comparable to the application of vacuum therapy in cutaneous wounds. The system is changed every 3-5 d. The overall success rate of EVT in the literature ranges from 84% to 100%, with a mean of 90%; only few complications have been reported. OTSCs are loaded on a transparent cap which is mounted on the tip of a standard endoscope. By bringing the edges of the perforation into the cap, by suction or by dedicated devices, such as anchor or twin grasper, the OTSC can be placed to close the perforation. For acute endoscopy associated perforations, the mean success rate is 90% (range: 70%-100%). For other types of perforations (postoperative, other chronic leaks and fistulas) success rates are somewhat lower (68%, and 59%, respectively). Only few complications have been reported. Although first reports are promising, further studies are needed to define the exact role of EVT and OTSC in treatment algorithms of upper gastrointestinal perforations. © 2014 Baishideng Publishing Group Inc. All rights reserved.