TY - JOUR A1 - Neuschäfer-Rube, Frank A1 - Oppermann, Martin A1 - Möller, Ulrike A1 - Böer, Ulrike A1 - Püschel, Gerhard Paul T1 - Agonist-induced phosphorylation by G protein-coupled receptor kinases of the EP4 receptor carboxyl-terminal domain in an EP3/EP4 prostaglandin E(2) receptor hybrid N2 - Prostaglandin E(2) receptors (EP-Rs) belong to the family of heterotrimeric G protein-coupled ectoreceptors with seven transmembrane domains. They can be subdivided into four subtypes according to their ligand-binding and G protein-coupling specificity: EP1 couple to G(q), EP2 and EP4 to G(s), and EP3 to G(i). The EP4-R, in contrast to the EP3beta-R, shows rapid agonist-induced desensitization. The agonist-induced desensitization depends on the presence of the EP4-R carboxyl-terminal domain, which also confers desensitization in a G(i)-coupled rEP3hEP4 carboxyl-terminal domain receptor hybrid (rEP3hEP4-Ct-R). To elucidate the possible mechanism of this desensitization, in vivo phosphorylation stimulated by activators of second messenger kinases, by prostaglandin E(2), or by the EP3-R agonist M&B28767 was investigated in COS-7 cells expressing FLAG-epitope-tagged rat EP3beta-R (rEP3beta-R), hEP4-R, or rEP3hEP4- Ct-R. Stimulation of protein kinase C with phorbol-12-myristate-13-acetate led to a slight phosphorylation of the FLAG- rEP3beta-R but to a strong phosphorylation of the FLAG-hEP4-R and the FLAG-rEP3hEP4-Ct-R, which was suppressed by the protein kinase A and protein kinase C inhibitor staurosporine. Prostaglandin E(2) stimulated phosphorylation of the FLAG- hEP4-R in its carboxyl-terminal receptor domain. The EP3-R agonist M&B28767 induced a time- and dose-dependent phosphorylation of the FLAG-rEP3hEP4-Ct-R but not of the FLAG-rEP3beta-R. Agonist-induced phosphorylation of the FLAG- hEP4-R and the FLAG-rEP3hEP4-Ct-R were not inhibited by staurosporine, which implies a role of G protein-coupled receptor kinases (GRKs) in agonist-induced receptor phosphorylation. Overexpression of GRKs in FLAG-rEP3hEP4-Ct-R- expressing COS-7 cells augmented the M&B28767-induced receptor phosphorylation and receptor sequestration. These findings indicate that phosphorylation of the carboxyl-terminal hEP4-R domain possibly by GRKs but not by second messenger kinases may be involved in rapid agonist-induced desensitization of the hEP4-R and the rEP3hEP4-Ct-R. Y1 - 1999 SN - 1521-0111 ER - TY - JOUR A1 - Böer, Ulrike A1 - Neuschäfer-Rube, Frank A1 - Möller, Ulrike A1 - Püschel, Gerhard Paul T1 - Requirement of N-glycosylation of the prostaglandin E2 receptor EP3beta for correct sorting to the plasma membrane but not for correct folding N2 - Eight heptahelical receptors have been characterized for prostaglandin (PG) D(2), PGE(2), PGF(2alpha), prostacyclin and thromboxane A(2). They share a sequence identity of 40%. All of them have potential N-glycosylation sites. The current study analysed the role of the two N-glycosylation sites in the rat EP3beta-subtype PGE(2) receptor for protein folding and sorting. The N-glycosylation consensus sequences were eliminated by site-directed mutagenesis and receptors expressed in HEK-293 cells. Both potential N-glycosylation sites were used. Their joint elimination resulted in the synthesis of a receptor protein with full binding competence, biological activity and no reduction of affinity; however, the half-life of the non-glycosylated receptor was slightly reduced. Ligand binding to intact stably transfected cells and confocal laser microscopic immunocytochemistry showed that the glycosylated receptor was correctly inserted into the plasma membrane to a much larger extent than the non-glycosylated receptor, which tended to accumulate in the perinuclear zone of the endoplasmic reticulum. Inhibition of N-glycosylation with tunicamycin resulted in a similar perinuclear distribution of the wild-type receptor. Therefore, glycosylation of the EP3beta receptor seems not to be necessary for correct folding of the receptor protein but for the efficient transport of the receptor protein to the plasma membrane. This contrasts with a previous finding which described a reduction of the affinity for PGE(2) of the EP3alpha receptor by elimination of the distal glycosylation site when the receptor protein was expressed in insect cells. Y1 - 2000 ER - TY - JOUR A1 - Gaeckle, Maren A1 - Domahs, Frank A1 - Kartmann, Angelika A1 - Tomandl, Bernd A1 - Frank, Ulrike T1 - Predictors of Penetration-Aspiration in Parkinson’s Disease Patients With Dysphagia BT - a retrospective analysis JF - Annals of Otology, Rhinology and Laryngology N2 - Methods: The data of 89 PD patients with dysphagia who underwent routinely conducted videofluoroscopic studies of swallowing (VFSS) were included in this retrospective study. The occurrence of penetration-aspiration was defined as scores >= 3 on the Penetration-Aspiration Scale (PAS). Four commonly reported signs of dysphagia in PD patients were evaluated as possible predictors. Furthermore, the relationships between the occurrence of penetration-aspiration and liquid bolus volume as well as clinical severity of PD (modified Hoehn and Yahr scale) were examined. Results: Logistic regression showed that a delayed initiation of the pharyngeal swallow (odds ratio [OR] = 7.47, P = .008) and a reduced hyolaryngeal excursion (OR = 5.13, P = .012) were predictors of penetration-aspiration. Moreover, there was a strong, positive correlation between increasing liquid bolus volume and penetration-aspiration (gamma = 0.71, P < .001). No correlation was found between severity of PD and penetration-aspiration (gamma = 0.077, P = .783). Conclusion: Results of the present study allow for a better understanding of penetration-aspiration risk in PD patients. They are useful for treatment planning in order to improve safe oral intake and adequate nutrition. KW - pneumonia KW - videofluoroscopy Y1 - 2019 U6 - https://doi.org/10.1177/0003489419841398 SN - 0003-4894 SN - 1943-572X VL - 128 IS - 8 SP - 728 EP - 735 PB - Sage Publ. CY - Thousand Oaks ER - TY - JOUR A1 - Schlickewei, Ole A1 - Nienstedt, Julie Cläre A1 - Frank, Ulrike A1 - Fründt, Odette A1 - Pötter-Nerger, Monika A1 - Gerloff, Christian A1 - Buhmann, Carsten A1 - Müller, Frank A1 - Lezius, Susanne A1 - Koseki, Jana-Christiane A1 - Pflug, Christina T1 - The ability of the eating assessment tool‑10 to detect penetration and aspiration in Parkinson’s disease JF - European archives of oto-rhino-laryngology and head & neck N2 - Purpose: Dysphagia is common in patients with Parkinson's disease (PD) and often leads to pneumonia, malnutrition, and reduced quality of life. This study investigates the ability of the Eating Assessment Tool-10 (EAT-10), an established, easy self-administered screening tool, to detect aspiration in PD patients. This study aims to validate the ability of the EAT-10 to detect FEES-proven aspiration in patients with PD. Methods: In a controlled prospective cross-sectional study, a total of 50 PD patients completed the EAT-10 and, subsequently, were examined by Flexible Endoscopic Evaluation of Swallowing (FEES) to determine the swallowing status. The results were rated through the Penetration-Aspiration Scale (PAS) and data were analyzed retrospectively. Results: PAS and EAT-10 did not correlate significantly. Selected items of the EAT-10 could not predict aspiration or residues. 19 (38%) out of 50 patients with either penetration or aspiration were not detected by the EAT-10. The diagnostic accuracy was established at only a sufficient level (AUC 0.65). An optimal cut-off value of >= 6 presented a sensitivity of 58% and specificity of 82%. Conclusions: The EAT-10 is not suited for the detection of penetration and aspiration in PD patients. Therefore, it cannot be used as a screening method in this patient population. There is still a need for a valid, simple, and efficient screening tool to assist physicians in their daily diagnostics and to avoid clinical complications. KW - Parkinson's disease KW - dysphagia KW - questionnaire KW - screening Y1 - 2020 U6 - https://doi.org/10.1007/s00405-020-06377-x SN - 0937-4477 SN - 1434-4726 VL - 278 IS - 5 SP - 1661 EP - 1668 PB - Springer CY - Berlin ER - TY - JOUR A1 - Frank, Ulrike A1 - Frank, Katrin A1 - Zimmermann, Heinrich T1 - Effects of Respiratory Therapy (bagging) on Respiratory Function, Swallowing Frequency and Vigilance in Tracheotomized Patients in Early Neurorehabilitation JF - Pneumologie : Zeitschrift für Pneumologie und Beatmungsmedizin N2 - Objective: Tracheotomized patients often suffer from impairments in mucociliary clearance and limited capacities for active expectoration of secretions. We investigated the effects of a specific respiratory intervention method (bagging) for tracheotomized patients on respiratory parameters (pO(2), pCO(2), SpO(2), respiratory rates), swallowing frequency, vigilance and secretion viscosity. Methods: The bagging method supports enforced mobilization and expectoration of secretions by application of a series of manual hyperinflations with a resuscitation bag during active inspiration and manual cough support on the chest. 30 tracheotomized neurological patients participated in a multiple-baseline study including a three-weeks intervention period and a follow-up measurement three weeks after termination of the treatment. Results: Most outcome parameters improved significantly during the intervention period: pO(2) (p<.01), SpO(2) (p<.01), respiratory rates (p<.01), swallowing rates (p<.01), and vigilance scores (p<.01). The quality of bronchial secretions improved in all participants. All effects were sustained up to the follow-up measurements. Conclusion: This preliminary data indicates positive effects for a respiratory intervention method (bagging) on respiratory function and additional respiration-related functions in tracheotomized neurological patients. This easy-to-learn and inexpensive method might expand the range of treatment options for tracheotomized and non-responsive patients. Y1 - 2015 U6 - https://doi.org/10.1055/s-0034-1392359 SN - 0934-8387 SN - 1438-8790 VL - 69 IS - 7 SP - 394 EP - 399 PB - Thieme CY - Stuttgart ER - TY - JOUR A1 - van der Valk, Ralf J. P. A1 - Kreiner-Moller, Eskil A1 - Kooijman, Marjolein N. A1 - Guxens, Monica A1 - Stergiakouli, Evangelia A1 - Saaf, Annika A1 - Bradfield, Jonathan P. A1 - Geller, Frank A1 - Hayes, M. Geoffrey A1 - Cousminer, Diana L. A1 - Koerner, Antje A1 - Thiering, Elisabeth A1 - Curtin, John A. A1 - Myhre, Ronny A1 - Huikari, Ville A1 - Joro, Raimo A1 - Kerkhof, Marjan A1 - Warrington, Nicole M. A1 - Pitkanen, Niina A1 - Ntalla, Ioanna A1 - Horikoshi, Momoko A1 - Veijola, Riitta A1 - Freathy, Rachel M. A1 - Teo, Yik-Ying A1 - Barton, Sheila J. A1 - Evans, David M. A1 - Kemp, John P. A1 - St Pourcain, Beate A1 - Ring, Susan M. A1 - Smith, George Davey A1 - Bergstrom, Anna A1 - Kull, Inger A1 - Hakonarson, Hakon A1 - Mentch, Frank D. A1 - Bisgaard, Hans A1 - Chawes, Bo Lund Krogsgaard A1 - Stokholm, Jakob A1 - Waage, Johannes A1 - Eriksen, Patrick A1 - Sevelsted, Astrid A1 - Melbye, Mads A1 - van Duijn, Cornelia M. A1 - Medina-Gomez, Carolina A1 - Hofman, Albert A1 - de Jongste, Johan C. A1 - Taal, H. Rob A1 - Uitterlinden, Andre G. A1 - Armstrong, Loren L. A1 - Eriksson, Johan A1 - Palotie, Aarno A1 - Bustamante, Mariona A1 - Estivill, Xavier A1 - Gonzalez, Juan R. A1 - Llop, Sabrina A1 - Kiess, Wieland A1 - Mahajan, Anubha A1 - Flexeder, Claudia A1 - Tiesler, Carla M. T. A1 - Murray, Clare S. A1 - Simpson, Angela A1 - Magnus, Per A1 - Sengpiel, Verena A1 - Hartikainen, Anna-Liisa A1 - Keinanen-Kiukaanniemi, Sirkka A1 - Lewin, Alexandra A1 - Alves, Alexessander Da Silva Couto A1 - Blakemore, Alexandra I. F. A1 - Buxton, Jessica L. A1 - Kaakinen, Marika A1 - Rodriguez, Alina A1 - Sebert, Sylvain A1 - Vaarasmaki, Marja A1 - Lakka, Timo A1 - Lindi, Virpi A1 - Gehring, Ulrike A1 - Postma, Dirkje S. A1 - Ang, Wei A1 - Newnham, John P. A1 - Lyytikainen, Leo-Pekka A1 - Pahkala, Katja A1 - Raitakari, Olli T. A1 - Panoutsopoulou, Kalliope A1 - Zeggini, Eleftheria A1 - Boomsma, Dorret I. A1 - Groen-Blokhuis, Maria A1 - Ilonen, Jorma A1 - Franke, Lude A1 - Hirschhorn, Joel N. A1 - Pers, Tune H. A1 - Liang, Liming A1 - Huang, Jinyan A1 - Hocher, Berthold A1 - Knip, Mikael A1 - Saw, Seang-Mei A1 - Holloway, John W. A1 - Melen, Erik A1 - Grant, Struan F. A. A1 - Feenstra, Bjarke A1 - Lowe, William L. A1 - Widen, Elisabeth A1 - Sergeyev, Elena A1 - Grallert, Harald A1 - Custovic, Adnan A1 - Jacobsson, Bo A1 - Jarvelin, Marjo-Riitta A1 - Atalay, Mustafa A1 - Koppelman, Gerard H. A1 - Pennell, Craig E. A1 - Niinikoski, Harri A1 - Dedoussis, George V. A1 - Mccarthy, Mark I. A1 - Frayling, Timothy M. A1 - Sunyer, Jordi A1 - Timpson, Nicholas J. A1 - Rivadeneira, Fernando A1 - Bonnelykke, Klaus A1 - Jaddoe, Vincent W. V. T1 - A novel common variant in DCST2 is associated with length in early life and height in adulthood JF - Human molecular genetics N2 - Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 x 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; beta = 0.046, SE = 0.008, P = 2.46 x 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 x 10(-4)) and adult height (N = 127 513; P = 1.45 x 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height. Y1 - 2015 U6 - https://doi.org/10.1093/hmg/ddu510 SN - 0964-6906 SN - 1460-2083 VL - 24 IS - 4 SP - 1155 EP - 1168 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Gervais, Frank A1 - Siedel, Ulrike A1 - Heilmann, Britta A1 - Weithoff, Guntram A1 - Heisig-Gunkel, Gabriele A1 - Nicklisch, Andreas T1 - Small-scale vertical distribution of phytoplankton, nutrients and sulphide below the oxicline of a mesotrophic lake N2 - A characteristic vertical sequence of phytoplankton populations was observed below the metalimnetic oxycline of a stratified, mesotrophic lake. Ceratium spp., Closterium acutum and Aphanizomenon flos- aquae were present in the epilimnion but had distinct population maxima in the microaerobic chemocline. Below these populations, Cryptomonas phaseolus, Planktothrix clathrata, Pseudanabaena catenata and Limnothrix sp. followed each other in the transition zone between the chemocline and the sulphide-containing hypolimnion. The dominating populations of P. clathrata and P. catenata caused a deep chlorophyll maximum. Phytoplankton structure was determined by the vertical gradients of sulphide and light. Compared with the epilimnion, nutrient availability was not fundamentally better below the oxycline but the algae might have benefited from reduced grazing pressure in their habitat. Y1 - 2003 UR - http://plankt.oupjournals.org/cgi/content/full/25/3/273 ER - TY - GEN A1 - Embs, Frank A1 - Funhoff, Dirk A1 - Laschewsky, André A1 - Licht, Ulrike A1 - Ohst, Holger A1 - Prass, Werner A1 - Ringsdorf, Helmut A1 - Wegner, Gerhard A1 - Wehrmann, Rolf T1 - Preformed polymers for Langmuir-Blodgett films- molecular concepts N2 - The use of preformed polymers for the preparation of Langmuir-Blodgett (LB) multilayers is reviewed. Principles for polymer self-organization are outlined and the appropriate molecular designs are discussed. Recent developments in the different classes of polymers for LB multilayers are presented, and their outstanding properties highlighted. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - paper 081 KW - Amphiphilic Polymers KW - Rod-like Polymers KW - LCPs KW - Stability of LB Films Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-17196 ER - TY - JOUR A1 - Huckabee, Maggie-Lee A1 - McIntosh, Theresa A1 - Fuller, Laura A1 - Curry, Morgan A1 - Thomas, Paige A1 - Walshe, Margaret A1 - McCague, Ellen A1 - Battel, Irene A1 - Nogueira, Dalia A1 - Frank, Ulrike A1 - van den Engel-Hoek, Lenie A1 - Sella-Weiss, Oshrat T1 - The test of masticating and swallowing solids (TOMASS) BT - reliability, validity and international normative data JF - International Journal of language & communicaton disorders N2 - BackgroundClinical swallowing assessment is largely limited to qualitative assessment of behavioural observations. There are limited quantitative data that can be compared with a healthy population for identification of impairment. The Test of Masticating and Swallowing Solids (TOMASS) was developed as a quantitative assessment of solid bolus ingestion. AimsThis research programme investigated test development indices and established normative data for the TOMASS to support translation to clinical dysphagia assessment. Conclusions & ImplicationsThe TOMASS is presented as a valid, reliable and broadly normed clinical assessment of solid bolus ingestion. Clinical application may help identify dysphagic patients at bedside and provide a non-invasive, but sensitive, measure of functional change in swallowing. KW - deglutition KW - assessment KW - mastication KW - swallowing KW - timed KW - solid Y1 - 2018 U6 - https://doi.org/10.1111/1460-6984.12332 SN - 1368-2822 SN - 1460-6984 VL - 53 IS - 1 SP - 144 EP - 156 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Frank, Ulrike A1 - van den Engel-Hoek, Lenie A1 - Nogueira, Dalia A1 - Schindler, Antonio A1 - Adams, Sasha A1 - Curry, Morgan A1 - Huckabee, Maggie-Lee T1 - International standardisation of the test of masticating and swallowing solids in children JF - Journal of oral rehabilitation N2 - The Test of Masticating and Swallowing Solids (TOMASS) is a validated assessment tool measuring the efficiency of solid bolus intake by four quantitative parameters: discrete bites, masticatory cycles, swallows and time to ingest a single cracker. A normative database for adults (20-80+ years) has previously been established. The objective of this study was to investigate the applicability and reliability of the TOMASS in children and adolescents (TOMASS-C) and to establish the normative database for this younger population. We collected data from 638 participants (male: 311, female: 327) in five age groups (4-18 years) with five different but very similar test crackers in four countries. Significant effects of bolus type (cracker), age group and gender on the TOMASS parameters were identified, requiring stratification of the TOMASS-C database by these variables. Intra-rater reliability was excellent (ICC > 0.94) for all parameters; inter-rater reliability was moderate for "number of swallows" (ICC = 0.54), good for "bites" (ICC = 0.78) and "time" (ICC = 0.82), and excellent for "masticatory cycles" (ICC = 0.96). The "Test of Masticating and Swallowing Solids in Children (TOMASS-C)" was identified to be a reliable diagnostic tool for the comprehensive measurement of discrete oral stage components of solid bolus ingestion, standardised by a large normative database that covers age groups from preschoolers to young adults. While differences between gender groups were less pronounced than in the adult population, previous results relating to changes in masticatory and swallowing as a function of age are confirmed by our data. KW - mastication KW - normative data KW - reliability KW - solid bolus KW - swallowing Y1 - 2018 U6 - https://doi.org/10.1111/joor.12728 SN - 0305-182X SN - 1365-2842 VL - 46 IS - 2 SP - 161 EP - 169 PB - Wiley CY - Hoboken ER -