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A novel common variant in DCST2 is associated with length in early life and height in adulthood
(2015)
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.
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.
COVID-19
(2022)
Eine COVID-19-Erkrankung kann zu schweren Krankheitsverläufen mit multiplen Organbeteiligungen und respiratorischen und neurologischen Funktionseinschränkungen führen. Schluckstörungen (Dysphagien) können in dieser Patientengruppe durch primäre Schädigungen des zentralen und peripheren neuronalen Netzwerkes der Schluckfunktion entstehen, aber auch bedingt durch die häufig längere intensivmedizinische Behandlung und Beatmung. Erste klinische Befunde zeigen persistierende Dysphagien im Rahmen des Post-COVID-Syndroms („Long-COVID“), sodass die Patienten auch längerfristige Maßnahmen zur Rehabilitation einer sicheren und suffizienten oralen Nahrungsaufnahme benötigen. Daher sollte in die Behandlung von COVID-19-Patienten ein strukturiertes erkrankungsspezifisches Monitoring in Bezug auf Dysphagiesymptome integriert werden, und atemtherapeutische Maßnahmen zur Regulation von Husteneffektivität und Atem-Schluck-Koordination sollten auch bei diesen Patienten essenzieller Bestandteil des Dysphagiemanagements sein. Herausforderungen ergeben sich dabei einerseits durch die erforderlichen Anpassungen etablierter Behandlungsstandards an den Infektionsschutz. Zudem müssen Auswahl und Durchführungsintensität therapeutischer Maßnahmen an die Kapazitäten und die spezifische Pathophysiologie der COVID-19- und Long-COVID-Patienten angepasst werden, um weitere funktionelle Verschlechterungen zu vermindern.
In der neurologischen Rehabilitation werden in zunehmendem Maße tracheotomierte Patienten mit schweren Dysphagien behandelt. Daher sollte den hierzu bisher entwickelten Interventionsverfahren eine evidenzbasierte Grundlage gegeben werden. In der vorliegenden Arbeit wird ein multidisziplinärer Behandlungsansatz zur Trachealkanülenentwöhung und Dekanülierung vorgestellt, der auf der Grundlage der relevanten Forschungsliteratur und klinischen Beobachtungen entwickelt wurde. Des Weiteren wird erstmals eine systematische Evaluation eines multidisziplinären Trachealkanülenmangements vorgenommen und es werden explorative Daten zum Rehabilitationsverlauf dargestellt. In einem retrospektiven Vergleich wurden hierzu die Dekanülierungs- und Komplikationsraten sowie die Dauer der Trachealkanülenentwöhnung zweier Patientengruppen gegenübergestellt, die vor bzw. nach Einführung des beschriebenen multidisziplinären Trachealkanülenmanagements im REHAB Basel, Schweiz, behandelt wurden. Der rehabilitative Verlauf der multidisziplinär behandelten Gruppe wurde mittels der Messinstrumente FIM (Functional Independence Measure) und EFA (Early Functional Abilities) untersucht. Der Vergleich der Dekanülierungs- und Komplikationsraten ergab eine vergleichbare Effektivität der beiden Behandlungsansätze. Darüber hinaus zeigte sich eine signifikante Verkürzung der Kanülenentwöhnungsphase bei Anwendung des multidisziplinären Vorgehens, so dass dieses als effizenter zu beurteilen ist. Die Verlaufsanalyse der multidisziplinär behandelten Patienten ergab erst nach der Dekanülierung einen signifikanten Zuwachs der funktionellen Selbständigkeit in Alltagsaktivitäten. Bei der Mehrzahl der Patienten konnte ein vollständiger oraler Kostaufbau nach der Dekanülierung erreicht werden.
Invasive alien species pose a great threat to the integrity of natural communities by competition with and predation on native species. In Germany the invasive raccoon dog (Nyctereutes procyonoides) and the native red fox (Vulpes vulpes) occupy a similar ecological niche. Therefore, the aim of our study was to discover the extent of exploitative diet competition between these two generalist carnivores. Carcasses of red foxes (n=256) and raccoon dogs (n=253) were collected throughout Mecklenburg Western-Pomerania (north-east Germany) and stomachs contains were analysed. Frequency of occurrence and biomass share indicate that both canids are omnivorous and pursue opportunistic feeding strategies. Small mammals and edible plant material were the most important food resources for red foxes and raccoon dogs. Nonetheless, interspecies differences were recorded for edible plant material, small mammals and insects. While red foxes mostly feed on voles, raccoon dogs consumed mice and shrews as often as voles. Only raccoon dogs preyed on amphibians. There were no differences in carrion consumption, both species scavenged on wild boar and we found clear competition for carrion year-round. Moreover, there was evidence that two red foxes foraged on raccoon dogs and vice versa. The mean annual interspecies diet overlap index was relatively high. The diets determined for raccoon dogs and red foxes were quite similar and a similar food niche breadth was recorded. However, only minor competition is assumed to take place since differences in feeding habits do exist.
Background
Simple water-swallowing screening tools are not predictive of aspiration and dysphagia in patients with Parkinson's Disease (PD). We investigated the diagnostic accuracy of a multi-texture screening tool, the Gugging Swallowing Screen (GUSS) to identify aspiration and dysphagia/penetration in PD patients compared to flexible endoscopic evaluation of swallowing (FEES).
Methods
Swallowing function was evaluated in 51 PD participants in clinical 'on-medication' state with the GUSS and a FEES examination according to standardized protocols. Inter-rater reliability and convergent validity were determined and GUSS- and FEES-based diet recommendations were compared.
Key Results
Inter-rater reliability of GUSS ratings was high (r(s) = 0.8; p < 0.001). Aspiration was identified by the GUSS with a sensitivity of 50%, and specificity of 51.35% (PPV 28%, NPV 73%, LR+ 1.03, LR- 0.97), dysphagia/penetration was identified with 72.97% sensitivity and 35.71% specificity (PPV 75%, NPV 33.33%, LR+ 1.14, LR- 0.76). Agreement between GUSS- and FEES-based diet recommendations was low (r(s) = 0.12, p = 0.42) with consistent NPO (Nil per Os) allocation by GUSS and FEES in only one participant.
Conclusions and Inferences
The multi-texture screening tool GUSS in its current form, although applicable with good inter-rater reliability, does not detect aspiration in PD patients with acceptable accuracy. Modifications of the GUSS parameters "coughing," "voice change" and "delayed swallowing" might enhance validity. The GUSS' diet recommendations overestimate the need for oral intake restriction in PD patients and should be verified by instrumental swallowing examination.
Background
Simple water-swallowing screening tools are not predictive of aspiration and dysphagia in patients with Parkinson's Disease (PD). We investigated the diagnostic accuracy of a multi-texture screening tool, the Gugging Swallowing Screen (GUSS) to identify aspiration and dysphagia/penetration in PD patients compared to flexible endoscopic evaluation of swallowing (FEES).
Methods
Swallowing function was evaluated in 51 PD participants in clinical 'on-medication' state with the GUSS and a FEES examination according to standardized protocols. Inter-rater reliability and convergent validity were determined and GUSS- and FEES-based diet recommendations were compared.
Key Results
Inter-rater reliability of GUSS ratings was high (r(s) = 0.8; p < 0.001). Aspiration was identified by the GUSS with a sensitivity of 50%, and specificity of 51.35% (PPV 28%, NPV 73%, LR+ 1.03, LR- 0.97), dysphagia/penetration was identified with 72.97% sensitivity and 35.71% specificity (PPV 75%, NPV 33.33%, LR+ 1.14, LR- 0.76). Agreement between GUSS- and FEES-based diet recommendations was low (r(s) = 0.12, p = 0.42) with consistent NPO (Nil per Os) allocation by GUSS and FEES in only one participant.
Conclusions and Inferences
The multi-texture screening tool GUSS in its current form, although applicable with good inter-rater reliability, does not detect aspiration in PD patients with acceptable accuracy. Modifications of the GUSS parameters "coughing," "voice change" and "delayed swallowing" might enhance validity. The GUSS' diet recommendations overestimate the need for oral intake restriction in PD patients and should be verified by instrumental swallowing examination.
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.
- Ulrike Leitner: Einleitung
- Frank Baron: From Alexander von Humboldt to Frederic Edwin Church: Voyages of Scientific Exploration and Artistic Creativity
- Rex Clark: Alexander von Humboldt‘s Images of Landscape and the ‚Chaos of the Poets
- Detlev Doherr: The Humboldt Digital Library: Exploring Innovative Structures
- Wolfgang Griep: Die Bedeutung der Umkreisquellen für Alexander von Humboldts südamerikanische Reise
- Ulrike Leitner: Vielschichtigkeit und Komplexität im Reisewerk Alexander von Humboldts – Bibliographischer Hintergrund
- Markus Schnoepf: El Proyecto Humboldt: Una biblioteca digital para las expediciones científicas a las Islas Canarias
Inhalt:
Alexander von Humboldt-Forschungsstelle: Ingo Schwarz zum 65. Geburtstag
Ottmar Ette: Findung und Erfindung einer Leserschaft. Neuere Editionsprojekte zu Alexander von Humboldt als Grundlage und Herausforderung künftigen Forschens
Eberhard Knobloch: Alexandre de Humboldt et le Marquis de Laplace
Oliver Schwarz: Alexander von Humboldt als astronomischer Arbeiter, Diskussionspartner und Ideengeber
Petra Werner: Innenwelten und bleiche Gärten. Alexander von Humboldt untertage und in der Caripe-Höhle
Christian Suckow: Alexander von Humboldt in Ust’-Kamenogorsk
Anne Jobst: Neue Briefe Christian Gottfried Ehrenbergs an Alexander von Humboldt
Thomas Schmuck: Humboldt, Baer und die Evolution
Manfred Ringmacher: Zwei Briefe auf Guaraní in Alexander von Humboldts Handschrift
Ute Tintemann: Julius Klaproths Mithridates-Projekt, Alexander von Humboldt und das Verlagshaus Cotta
Ulrike Leitner: „Ja! Wenn Berlin Bonn wäre!“ Friedrich Rückerts Berufung nach Berlin
Frank Holl: „Zur Freiheit bestimmt“ – Alexander von Humboldts Blick auf die Kulturen der Welt
Sebastian Panwitz: Das Humboldt-Mendelssohn-Haus Jägerstraße 22. Ein Quellenfund
Laura Péaud: Du Mexique à l‘Oural : l‘expertise humboldtienne au service du politique
Bärbel Holtz: „Cicerone“ des Königs? Alexander von Humboldt und Friedrich Wilhelm III.
Menso Folkerts: Ein unerwartetes Zusammentreffen in Sanssouci. Alexander von Humboldt und Karl Ludwig Hencke an der Tafel Friedrich Wilhelms IV.
Ulrich Päßler: Preußens Mann in Washington. Fünf Briefe Friedrich von Gerolts an Alexander von Humboldt (1858/1859)
Bill Roba: German-Iowan Strategies in Celebrating the Centennial of Alexander von Humboldt’s Birth
Regina Mikosch: Ingo Schwarz‘ Veröffentlichungen zur Alexander von Humboldt
Über die Autoren
Prostanoid receptors belong to the class of heptahelical plasma membrane receptors. For the five prostanoids, eight receptor subtypes have been identified. They display an overall sequence similarity of roughly 30%. Based on sequence comparison, single amino acids in different subtypes of different species have previously been identified by site-directed mutagenesis or in hybrid receptors that appear to be essential for ligand binding or G-protein coupling. Based on this information, a series of mutants of the human FP receptor was generated and characterized in ligand- binding and second-messenger-formation studies. It was found that mutation of His-81 to Ala in transmembrane domain 2 and of Arg-291 to Leu in transmembrane domain 7, which are putative interaction partners for the prostanoid's carboxyl group, abolished ligand binding. Mutants in which Ser-263 in transmembrane domain 6 or Asp-300 in transmembrane domain 7 had been replaced by Ala or Gln, respectively, no longer discriminated between prostaglandins PGF(2alpha) and PGD(2). Thus distortion of the topology of transmembrane domains 6 and 7 appears to interfere with the cyclopentane ring selectivity of the receptor. PGF(2alpha)-induced inositol formation was strongly reduced in the mutant Asp-300Gln, inferring a role for this residue in agonist-induced G-protein activation.