Rasterelektronenmikroskopische Untersuchungen zu möglichen Mikrosymptomen der ektodermalen Dysplasie bei Patienten mit multiplen Nichtanlagen bleibender Zähne

Es wurde untersucht, ob sich bei Patienten mit multiplen Nichtanlagen bleibender Zähne Mikrosymptome ektodermaler Dysplasien in anderen Geweben bzw. Organen ektodermalen Ursprungs finden lassen. Dazu wurde bei 28 Patienten mit multiplen Nichtanlagen bleibender Zähne, und 14 Kontrollprobanden ohne Nichtanlagen die Schweißporendichte auf den Fingerkuppen ermittelt, um festzustellen, ob Patienten mit Nichtanlagen bleibender Zähne eine verringerte Schweißporendichte haben, so wie Patienten, die unter bestimmten Formen ektodermaler Dysplasien leiden. Es wurden bei allen Teilnehmern der Studie Abformungen der Fingerkuppen mit einem dünnfließenden Silikon gemacht. Auf diesen Abformungen wurden dann mithilfe eines Rasterelektronenmikroskops die Anzahl der Schweißporen in einem definierten Areal mit zwei verschiedenen Methoden gezählt. Die statistische Auswertung ergab, dass die mittlere Schweißporendichte auf den Fingerkuppen in der Patientengruppe kleiner war als in der Kontrollgruppe

Towards timing and stratigraphy of the Bronze Age burial mound royal tomb (Königsgrab) of Seddin (Brandenburg, northeastern Germany)

This study uses an integrated multi-method geoarcheological and geochronological approach to contribute to the understanding of the timing and stratigraphy of the monumental burial mound royal tomb (Königsgrab) of Seddin. We show that the hitherto established radiocarbon-based terminus post quem time frame for the construction of the burial mound of 910–800 BCE is supported by optically stimulated luminescence (OSL) dating. The radiocarbon samples were obtained from a substrate directly underneath the burial mound which supposedly represents the late glacial/Holocene soil that was buried below the structure. We use sedimentological (grain-size analyses) and geochemical analyses (element analyses, carbon, pH, and electric conductivity determinations) to reassess and confirm this hypothesis. In addition to the burial age associated with the last anthropogenic reworking during construction of the burial mound, the OSL dating results provide new insights into the primary deposition history of the original substrates used for the structure. In combination with regional information about the middle and late Quaternary development of the environment, our data allow us to provide a synoptic genetic model of the landscape development and the multiphase stratigraphy of the royal tomb of Seddin within the Late Bronze Age cultural group “Seddiner Gruppe” of northern Germany. Based on our initial experiences with OSL dating applied to the sediments of a burial mound – to the best of our knowledge the first attempt in Europe – we propose a minimal invasive approach to obtain datable material from burial mounds and discuss related opportunities and challenges

Accurate Transponder Calibrations with the Novel Three-Transponder Method

Transponders are, besides trihedral corner reflectors, the most commonly used measurement standards in radiometric SAR calibration. They allow signal recording for the reconstruction of the azimuth pattern of the SAR system, adjustments of the backscattering matrix for polarimetric applications, and radar cross sections (RCSs) which are potentially much larger than those of passive point targets. These advantages led DLR to develop, manufacture, and install three new, accurate C-band “Kalibri” transponders in South Germany, which are now being used for the calibration and monitoring of the Copernicus Sentinel-1A satellite. Before the transponders could be used as radiometric measurement standards, they needed to be calibrated themselves. In an effort to find the most accurate RCS calibration approach for the given transponder design, several existing methods were compared [1], and a new, potentially highly accurate method, devised which exploits the specific design of the Kalibri transponders [2]. The new “three-transponder method” is similar in principle to the known “three-antenna method”, but is based on the radar equation instead of the Friis transmission formula. The approach exploits the fact that modern transponders like the “Kalibri” device can also be operated as radars because of the integrated digital sub-system (which is needed to implement a digital delay line and incorporates an AD and DA converter). To conduct a complete measurement, three transponders and three measurements (with one transponder pair each) are required; refined measurement schemas are also possible. In comparison to existing methods, no additional radiometric measurement standard is needed, which so far has been one of the limiting factors in accomplishing lower calibration uncertainties. Measurement traceability is achieved by tracing a comparatively simple length measurement back to a national realization of the meter. Such a length measurements can be performed with high accuracy. The presentation will include the setup and the measurement results of a first demonstration measurement campaign. Despite remaining challenges in the practical implementation, the uncertainty analysis shows that the method is a good candidate for highly accurate transponder RCS calibrations in the future

dPGS Regulates the Phenotype of Macrophages via Metabolic Switching

The synthetic compound dendritic polyglycerol sulfate (dPGS) is a pleiotropic acting molecule but shows a high binding affinity to immunological active molecules as L-/P-selectin or complement proteins leading to well described anti-inflammatory properties in various mouse models. In order to make a comprehensive evaluation of the direct effect on the innate immune system, macrophage polarization is analyzed in the presence of dPGS on a phenotypic but also metabolic level. dPGS administered macrophages show a significant increase of MCP1 production paralleled by a reduction of IL-10 secretion. Metabolic analysis reveals that dPGS could potently enhance the glycolysis and mitochondrial respiration in M0 macrophages as well as decrease the mitochondrial respiration of M2 macrophages. In summary the data indicate that dPGS polarizes macrophages into a pro-inflammatory phenotype in a metabolic pathway-dependent manner

Transcriptomic profiling of pancreatic alpha, beta and delta cell populations identifies delta cells as a principal target for ghrelin in mouse islets.

AIMS/HYPOTHESIS: Intra-islet and gut-islet crosstalk are critical in orchestrating basal and postprandial metabolism. The aim of this study was to identify regulatory proteins and receptors underlying somatostatin secretion though the use of transcriptomic comparison of purified murine alpha, beta and delta cells. METHODS: Sst-Cre mice crossed with fluorescent reporters were used to identify delta cells, while Glu-Venus (with Venus reported under the control of the Glu [also known as Gcg] promoter) mice were used to identify alpha and beta cells. Alpha, beta and delta cells were purified using flow cytometry and analysed by RNA sequencing. The role of the ghrelin receptor was validated by imaging delta cell calcium concentrations using islets with delta cell restricted expression of the calcium reporter GCaMP3, and in perfused mouse pancreases. RESULTS: A database was constructed of all genes expressed in alpha, beta and delta cells. The gene encoding the ghrelin receptor, Ghsr, was highlighted as being highly expressed and enriched in delta cells. Activation of the ghrelin receptor raised cytosolic calcium levels in primary pancreatic delta cells and enhanced somatostatin secretion in perfused pancreases, correlating with a decrease in insulin and glucagon release. The inhibition of insulin secretion by ghrelin was prevented by somatostatin receptor antagonism. CONCLUSIONS/INTERPRETATION: Our transcriptomic database of genes expressed in the principal islet cell populations will facilitate rational drug design to target specific islet cell types. The present study indicates that ghrelin acts specifically on delta cells within pancreatic islets to elicit somatostatin secretion, which in turn inhibits insulin and glucagon release. This highlights a potential role for ghrelin in the control of glucose metabolism.This work was supported by the European Foundation for the Study of Diabetes and Boehringer Ingelheim Basic Research Programme; the Wellcome Trust (grants 106262/Z/14/Z, 106263/Z/14/Z and 100574/ Z/12/Z); the Medical Research Council Metabolic Diseases Unit (grants MRC_MC_UU_12012/3 and MRC_MC_UU_12012/5); and the Novo Nordisk Foundation

Bile Acids Trigger GLP-1 Release Predominantly by Accessing Basolaterally Located G Protein-Coupled Bile Acid Receptors.

Bile acids are well-recognized stimuli of glucagon-like peptide-1 (GLP-1) secretion. This action has been attributed to activation of the G protein-coupled bile acid receptor GPBAR1 (TGR5), although other potential bile acid sensors include the nuclear farnesoid receptor and the apical sodium-coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release and to determine whether bile acids target their receptors on GLP-1-secreting L-cells from the apical or basolateral compartment. Using transgenic mice expressing fluorescent sensors specifically in L-cells, we observed that taurodeoxycholate (TDCA) and taurolithocholate (TLCA) increased intracellular cAMP and Ca(2+). In primary intestinal cultures, TDCA was a more potent GLP-1 secretagogue than taurocholate (TCA) and TLCA, correlating with a stronger Ca(2+) response to TDCA. Using small-volume Ussing chambers optimized for measuring GLP-1 secretion, we found that both a GPBAR1 agonist and TDCA stimulated GLP-1 release better when applied from the basolateral than from the luminal direction and that luminal TDCA was ineffective when intestinal tissue was pretreated with an ASBT inhibitor. ASBT inhibition had no significant effect in nonpolarized primary cultures. Studies in the perfused rat gut confirmed that vascularly administered TDCA was more effective than luminal TDCA. Intestinal primary cultures and Ussing chamber-mounted tissues from GPBAR1-knockout mice did not secrete GLP-1 in response to either TLCA or TDCA. We conclude that the action of bile acids on GLP-1 secretion is predominantly mediated by GPBAR1 located on the basolateral L-cell membrane, suggesting that stimulation of gut hormone secretion may include postabsorptive mechanisms.Mesoscale GLP-1 immuno assays were performed by Keith Burling and colleagues at the Medical Research Council Metabolic Diseases Unit, Cambridge. Thisworkwas supported by the Wellcome Trust (grants 084 210/Z/07/Z, 088 357/Z/09/Z and 099 825/Z/12/Z) and the MRC (grant MRC_MC_UU_12012/ 3), the Novo Nordisk Center for Basic Metabolic Research (Novo Nordisk Foundation, Denmark) and the European Union’s Seventh Framework Programme for Research, Technological Development, and Demonstration Activities (Grant No. 266 408) Juraj Rievaj was supported by an EFSD Albert Renold Travel Fellowship. Ussing chamber equipment was initially kindly lent by Dr. Todd Alexander, Departments of Pediatrics& Physiology, University of Alberta, Canada.This is the final version of the article. It first appeared from Endocrine Society via http://dx.doi.org/10.1210/en.2015-132