320 resultados para Lippen-Kiefer-Gaumenspalte
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Von Dr. Carl Freiherr von Tubeuf
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Von Dr. Carl Freiherr von Tubeuf
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Von Ernst H. L. Krause
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Von W. Sukatscheff
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Von Prof. Dr. August Schulz
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Signatur des Originals: S 36/F08938
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Mode of access: Internet.
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The extracellular loop 3 (ECL3) of the mammalian gonadotropin-releasing hormone receptor (GnRH-R) contains an acidic amino acid (Glu(301) in the mouse GnRH-R,) that confers agonist selectivity for Are in mammalian GnRH. It is proposed that a specific conformation of ECL3 is necessary to orientate the carboxyl side chain of the acidic residue for interaction with Arg(8) of GnRH, which is supported by decreased affinity for Arg(8) GnRH but not Gln(8) GnRH when an adjacent Pro is mutated to Ala. To probe the structural contribution of the loop domain to the proposed presentation of the carboxyl side chain, we synthesized a model peptide (CGPEMLNRVSEPGC) representing residues 293-302 of mouse ECL3, where Cys and Gly residues are added symmetrically at the N and C termini, respectively, allowing the introduction of a disulfide bridge to simulate the distances at which the ECL3 is tethered to the transmembrane domains 6 and 7 of the receptor. The ability of the ECL3 peptide to bind GnRH with low affinity was demonstrated by its inhibition of GnRH stimulation of inositol phosphate production in cells expressing the GnRH-R. The CD bands of the ECL3 peptides exhibited a superposition of predominantly unordered structure and partial contributions from beta-sheet structure. Likewise, the analysis of the amide I and amide III bands from micro-Raman and FT Raman experiments revealed mainly unordered conformations of the cyclic and of the linear peptide. NMR data demonstrated the presence of a beta-hairpin among an ensemble of largely disordered structures in the cyclic peptide. The location of the turn linking the two strands of the hairpin was assigned to the three central residues L-296, N-297, and R-298. A small population of structured species among an ensemble of predominantly random coil conformation suggests that the unliganded receptor represents a variety of structural conformers, some of which have the potential to make contacts with the ligand. We propose a mechanism of receptor activation whereby binding of the agonist to the inactive receptor state induces and stabilizes a particular structural state of the loop domain, leading to further conformational rearrangements across the transmembrane domain and signal propagating interaction with G proteins. Interaction of the Glu(301) of the receptor with Arg(8) of GnRH induces a folded configuration of the ligand. Our proposal thus suggests that conformational changes of both ligand and receptor result from this interaction.
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Este estudo teve o objetivo de avaliar planos de suplementação com ractopamina, em dietas sem ajustes aminoacídicos, para suínos machos castrados, em terminação. Foram utilizados 72 suínos machos castrados, com peso inicial de 68,61 ± 3,89 kg, distribuídos em seis planos de suplementação com duração de 30 dias (0 ppm; 5 ppm; 10 ppm; 20 ppm; 5 ppm, durante 15 dias, seguidos por 10 ppm durante 15 dias; e 10 ppm durante 15 dias seguidos por 20 ppm durante 15 dias), com seis repetições e dois animais por unidade experimental. A suplementação com ractopamina melhorou a conversão alimentar. A suplementação com 5 ppm de ractopamina aumentou o ganho de peso diário. Os níveis de 10 e 20 ppm e as suplementações graduais reduziram o consumo de ração diário e de nutrientes. Não houve influência da suplementação sobre o peso de carcaça quente e o comprimento de carcaça. A ractopamina reduziu a espessura de toucinho e aumentou a profundidade de músculo, o percentual de carne magra, a quantidade de carne magra e o índice de bonificação das carcaças. A suplementação de 5 ppm de ractopamina em dietas sem ajustes aminoacídicos melhora o desempenho e as características de carcaça de suínos em terminação, nos 30 dias pré-abate.
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Magdeburg, Univ., Med. Fak., Diss., 2013
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Die kaulquappe von Thoropa miliaris lebt in mittleren Lagen des Itatiáia-Gebirges (Staat Rio de Janeiro), in etwa 1650 m Hoebe, auf fast senkracht stehenden Felsplatten, ueber die staendig eine sehr duenne Schicht Wasser herablaeuft. Die Tiere haben keinen Flossensaum; der zwei- bis dreimal koerperlange Schwanz ist fast drehrund und besitzt an Stelle eines Flossensaumes nur einen ventralen Kiel, der die Schlaengelbewegung gegen den Wasserstrom unterstuetzt. Auch die juengsten Stadien haben keine aeusseren kiemen, sondern innere in einer Atemhoehle, deren Ausgang sich auf der linken Seite in der Mitte des Koerpers befindet. Die Tiere heften sich an den Steinen vermittels ihres sehr grossen Mundapparates fest. Die Lippen tragen zwei oder drei Reihen starker Keratin-Haken, die durch laufende Neubildung ersetzt werden. Die arbeitenden Spitzenzaehne des Hornschnabels in der Mundhoehle werden ebenfalls durch fortgesetztes Wachstum erneuert. Die Saugscheibenwirkung des Mundes wird durch ein Muskelpaar bedingt, das einerseits am Parasphenoid- und am Sphenethmoidknorpel, andererseits mit seinen unteren Buendeln am Prodentale (Spitze des Meckel'schen Knorpels), mit seinem oberen vermittels je zweier Sehnen am Promaxillare ansetzt. Durch die kontraktion dieser Muskeln wird das Prodentale nach oben und dann nach hinten, das Promaxillare (mit Gelenkstellen am Prointermaxillare und Pronasale) nach oben und dann nach vorne gedreht. Hierdurch treten die beiden Kegel des Hornschnabels in die Mundhoehle, da sie den beiden Knorpeln fest aufsitzen. Bei starker Kontraktion werden die Knorpel auseinander gedrueckt und vergroessern die Mundhoehle. Wenn die Lippen, unterstuetzt von den Hakenreihen, fest dem Stein aufliegen, ergibt sich ein Unterdruck in der Mundhoehle, der genuegt, um die Larven auf der Unterlage festzuhalten. Das Loesen des Saugnapfes erfolgt durch die kontraktion einer Gruppe kleiner Muskelbuendel, die einerseits am Unterrand des Prodentale, andererseits an den falten der Unterlippe ansetzen.
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Die Autoren bearbeiten in der vorliegenden Arbeit die bulimuliden Pulmonaten Cochlorina aurisleporis (Bruguiére, 1792), wobei sie insbesondere auf die anatomischen und histologischen Verhaeltnisse des Geschlechtsapparates eingehen und Schale, Kiefer und Lunge mit in die Betrachtung einbeziehen, um die Charaktere der Art anatomisch zu festigen.
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Introduction: We previously reported the results of a phase II study for patients with newly diagnosed primary CNS lymphoma (PCNSL) treated with autologous peripheral blood stem-cell transplantation (aPBSCT) and responseadapted whole brain radiotherapy (WBRT). The purpose of this report is to update the initial results and provide long-term data regarding overall survival, prognostic factors, and the risk of treatment-related neurotoxicity.Methods: A long-term follow-up was conducted on surviving primary central nervous system lymphoma patients having been treated according to the ,,OSHO-53 study", which was initiated by the Ostdeutsche Studiengruppe Hamatologie-Onkologie. Between August 1999 and October 2004 twentythree patients with an average age of 55 and median Karnofsky performance score of 70% were enrolled and received high-dose mthotrexate (HD-MTX) on days 1 and 10. In case of at least a partial remission (PR), high-dose busulfan/ thiotepa (HD-BuTT) followed by aPBSCT was performed. Patients without response to induction or without complete remission (CR) after HD-BuTT received WBRT. All patients (n=8), who are alive in 2011, were contacted and Mini Mental State examination (MMSE) and the EORTC QLQ-C30 were performed.Results: Eight patients are still alive with a median follow-up of 116,9 months (79 - 141, range). One of them suffered from a late relapse eight and a half years after initial diagnosis of PCNSL, another one suffers from a gall bladder carcinoma. Both patients are alive, the one with the relapse of PCNSL has finished rescue therapy and is further observed, the one with gall baldder carcinoma is still under therapy. MMSE and QlQ-C30 showed impressive results in the patients, who were not irradiated. Only one of the irradiated patients is still alive with a clear neurologic deficit but acceptable quality of life.Conclusions: Long-term follow-up of our patients, who were included in the OSHO-53 study show an overall survival of 30 percent. If WBRT can be avoided no long-term neurotoxicity has been observed and the patients benefit from excellent Quality of Life. Induction chemotherapy with two cycles of HD-MTX should be intensified to improve the unsatisfactory OAS of 30 percent.
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Lymphatic valves are essential for efficient lymphatic transport, but the mechanisms of early lymphatic-valve morphogenesis and the role of biomechanical forces are not well understood. We found that the transcription factors PROX1 and FOXC2, highly expressed from the onset of valve formation, mediate segregation of lymphatic-valve-forming cells and cell mechanosensory responses to shear stress in vitro. Mechanistically, PROX1, FOXC2, and flow coordinately control expression of the gap junction protein connexin37 and activation of calcineurin/NFAT signaling. Connexin37 and calcineurin are required for the assembly and delimitation of lymphatic valve territory during development and for its postnatal maintenance. We propose a model in which regionally increased levels/activation states of transcription factors cooperate with mechanotransduction to induce a discrete cell-signaling pattern and morphogenetic event, such as formation of lymphatic valves. Our results also provide molecular insights into the role of endothelial cell identity in the regulation of vascular mechanotransduction.
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Androgenetic alopecia (AGA) is a highly heritable condition and the most common form of hair loss in humans. Susceptibility loci have been described on the X chromosome and chromosome 20, but these loci explain a minority of its heritable variance. We conducted a large-scale meta-analysis of seven genome-wide association studies for early-onset AGA in 12,806 individuals of European ancestry. While replicating the two AGA loci on the X chromosome and chromosome 20, six novel susceptibility loci reached genome-wide significance (p = 2.62×10(-9)-1.01×10(-12)). Unexpectedly, we identified a risk allele at 17q21.31 that was recently associated with Parkinson's disease (PD) at a genome-wide significant level. We then tested the association between early-onset AGA and the risk of PD in a cross-sectional analysis of 568 PD cases and 7,664 controls. Early-onset AGA cases had significantly increased odds of subsequent PD (OR = 1.28, 95% confidence interval: 1.06-1.55, p = 8.9×10(-3)). Further, the AGA susceptibility alleles at the 17q21.31 locus are on the H1 haplotype, which is under negative selection in Europeans and has been linked to decreased fertility. Combining the risk alleles of six novel and two established susceptibility loci, we created a genotype risk score and tested its association with AGA in an additional sample. Individuals in the highest risk quartile of a genotype score had an approximately six-fold increased risk of early-onset AGA [odds ratio (OR) = 5.78, p = 1.4×10(-88)]. Our results highlight unexpected associations between early-onset AGA, Parkinson's disease, and decreased fertility, providing important insights into the pathophysiology of these conditions.