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Remodeling of the extracellular matrix is a key component of the metabolic adaptations of adipose tissue in response to dietary and physiological challenges. Disruption of its integrity is a well-known aspect of adipose tissue dysfunction, for instance, during aging and obesity. Adipocyte regeneration from a tissue-resident pool of mesenchymal stem cells is part of normal tissue homeostasis. Among the pathophysiological consequences of adipogenic stem cell aging, characteristic changes in the secretory phenotype, which includes matrix-modifying proteins, have been described. Here, we show that the expression of the matricellular protein periostin, a component of the extracellular matrix produced and secreted by adipose tissue-resident interstitial cells, is markedly decreased in aged brown and white adipose tissue depots. Using a mouse model, we demonstrate that the adaptation of adipose tissue to adrenergic stimulation and high-fat diet feeding is impaired in animals with systemic ablation of the gene encoding for periostin. Our data suggest that loss of periostin attenuates lipid metabolism in adipose tissue, thus recapitulating one aspect of age-related metabolic dysfunction. In human white adipose tissue, periostin expression showed an unexpected positive correlation with age of study participants. This correlation, however, was no longer evident after adjusting for BMI or plasma lipid and liver function biomarkers. These findings taken together suggest that age-related alterations of the adipose tissue extracellular matrix may contribute to the development of metabolic disease by negatively affecting nutrient homeostasis.
Ankommen
(2016)
Jaro und Malia sind endlich wieder mit ihren Kindern Juna, Nenad und Yasha zusammen. Endlich! Vor den klimatischen Veränderungen und den dadurch ausgelösten bürgerkriegsähnlichen Zuständen flohen sie. Der Vater ging mit der ältesten Tochter Juna zuerst, so hatten sie es beschlossen. Die Mutter folgte später mit den Kindern Nenad und Yasha. Nun wohnen sie in der winzigen Wohnung von Avron und versuchen, in Deutschland anzukommen. Dabei stellen sich ihnen nicht nur deutsche Wortmonster in den Weg. Alles ist neu: Die Stadt, in der sich Nenad noch nach Wochen verläuft; der Schnee, der zu Hause nicht fiel; die Formulare, die auf Ämtern auszufüllen sind und die Supermärkte, in denen es keine ganzen Hähne zu kaufen gibt. Nur die Zahlen und Zeichen der Mathematik sind überall gleich und geben zumindest Nenad Sicherheit. Noch mehr Geborgenheit erfährt die Familie jedoch durch ihre Religion. Wie in ihrem alten Zuhause gibt es auch hier Menschen, die sich versammeln um zu beten, zu feiern und zu singen. Aber sie treffen sich nicht in einer heiligen Grotte wie die Ahaqu. Besonders Malia, die Mutter, vermisst ihre Religion mit ihren naturverbundenen Bräuchen sehr.
„Ankommen“ thematisiert unaufdringlich das Verhältnis zwischen Religion und Migration anhand einer Familie, die aus einem unbekannten und nicht näher bezeichneten Land nach Deutschland kommt und einer fiktiven Religion angehört. Hier treffen sie nicht nur auf andere naturräumliche Gegebenheiten, sondern auch auf völlig andere gesellschaftlich-kulturell-religiöse Traditionen, wodurch es zu Irritationen und Missverständnissen kommt. Die elf Geschichten des Buches stehen jeweils für sich und thematisieren ein Element religiösen Lebens bzw. der Religion unter den Bedingungen des Ankommens in einem fremden Land. Zugleich sind alle Texte inhaltlich-thematisch miteinander verwoben. Dadurch ist es möglich, die Geschichten einzeln zu lesen oder das Buch als Ganzschrift. Für den Einsatz im wertebildenden und religionskundlichen Unterricht bietet das Buch am Ende jeder Geschichte ein didaktisches Setting an.
Fragestellung: Ziel war die Untersuchung des Verlaufs von Kindern mit Rechenstörungen bzw. Rechenschwächen. Neben der Persistenz wurden Auswirkungen von Rechenproblemen auf künftige Rechenleistungen sowie den Schulerfolg geprüft. Methodik: Für 2909 Schüler der 2. bis 5. Klasse liegen die Resultate standardisierter Rechen- und Intelligenztests vor. Ein Teil dieser Kinder ist nach 37 und 68 Mona-ten erneut untersucht worden. Ergebnisse: Die Prävalenz von Rechenstörungen betrug 1.4 %, Rechenschwächen traten bei 11.2 % auf. Rechen-probleme zeigten eine mittlere bis hohe Persistenz. Schüler mit Rechenschwäche blieben im Rechnen gut eine Standardabweichung hinter durchschnittlich und ca. eine halbe Standardabweichung hinter unterdurchschnittlich intelligenten Kontrollkindern zurück. Der allgemeine Schulerfolg rechenschwacher Probanden (definiert über Mathematiknote, Deutschnote und Schultyp) ähnelte dem der unterdurchschnittlich intelligenten Kontrollgruppe und blieb hinter dem Schulerfolg durchschnittlich intelligenter Kontrollkinder zurück. Eingangs ältere Probanden mit Rechenproblemen (4. bis 5. Klasse) wiesen eine schlechtere Prognose auf als Kinder, die zu Beginn die 2. oder 3. Klasse besuchten. Schluss-folgerungen: Rechenprobleme stellen ein ernsthaftes Entwicklungsrisiko dar. Längsschnittuntersuchungen, die Kinder mit streng definierter Rechenstörung bis ins Erwachsenenalter begleiten und Prädiktoren für unterschiedlich erfolgreiche Verläufe ermitteln, sind dringend notwendig.
The centrosome is the main microtubule-organizing center and constitutes the largest protein complex in a eukaryotic cell. The Dictyostelium centrosome is an established model for acentriolar centrosomes and it consists of a layered core structure Surrounded by a so-called corona, which harbors microtubule nucleation complexes. We have identified 34 new centrosomal candidate proteins through mass spectrometrical analysis of the proteome of isolated Dictyostelium centrosomes. Here we present a characterization of 12 centrosomal candidate proteins all featuring coiled coil regions and low expression levels, which are the most common attributes of centrosomal proteins. We used GFP fusion proteins to localize the candidate proteins in whole cells and on microtubule-free, isolated centrosomes. Thus we were able to identify nine new genuine centrosomal proteins including a putative orthologue of Cep192, an interaction partner of polo-like kinase 4 in human centriole biogenesis. In this respect, centrosomal localization of the only polo-like kinase in Dictyostelium, Pik, is also shown in this work. Using confocal deconvolution microscopy, four components, CP39, CP55, CP75, and CP91 could be clearly assigned to the so far almost uncharacterized centrosomal core structure, while CP148 and Cep192 localized to a zone between that of corona marker and core proteins. Finally, CP103 and CP248 were constituents of the corona. In contrast, NE81 was localized at the nuclear envelope and three others, an orthologue of the spindle checkpoint component Mad1, the novel Cenp68, and the centrosomal CP248 were observed at the centromeres, which are clustered and linked to the centrosome throughout the entire cell cycle. Cell Motil. Cytoskeleton 66: 915-928, 2009.
Cell cycle-dependent localization of novel centrosomal and centromeric proteins in Dictyostelium
(2009)
The endothelialization of synthetic surfaces applied as cardiovascular implant materials is an important issue to ensure the anti-thrombotic quality of a biomaterial. However, the rapid and constant development of a functionallycon-fluent endothelial cell monolayer is challenging. In order to investigate the compatibility of potential implant materials with endothelial cells several in vitro studies are performed. Here, glass and tissue culture plates (TCP) are often used as reference materials for in vitro pre-testing. However, a direct comparison of both substrates is lacking. Therefore, a comparison of study results is difficult, since results are often related to various reference materials. In this study, the endothelialization of glass and TCP was investigated in terms of adherence, morphology, integrity, viability and function using human umbilical vein endothelial cells (HUVEC). On both substrates an almost functionally confluent HUVEC monolayer was developed after nine days of cell seeding with clearly visible cell rims, decreased stress fiber formation and a pronounced marginal filament band. The viability of HUVEC was comparable for both substrates nine days after cell seeding with only a few dead cells. According to that, the cell membrane integrity as well as the metabolic activity showed no differences between TCP and glass. However, a significant difference was observed for the secretion of IL-6 and IL-8. The concentration of both cytokines, which are associated with migratory activity, was increased in the supernatant of HUVEC seeded on TCP. This result matches well with the slightly increased number of adherent HUVEC on TCP. In conclusion, these findings indicate that both reference materials are almost comparable and can be used equivalently as control materials in in vitro endothelialization studies.
Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are hepatic manifestations of the metabolic syndrome. Many currently used animal models of NAFLD/NASH lack clinical features of either NASH or metabolic syndrome such as hepatic inflammation and fibrosis (e.g., high-fat diets) or overweight and insulin resistance (e.g., methionine-choline-deficient diets), or they are based on monogenetic defects (e.g., ob/ob mice). In the current study, a Western-type diet containing soybean oil with high n-6-PUFA and 0.75% cholesterol (SOD + Cho) induced steatosis, inflammation and fibrosis accompanied by hepatic lipid peroxidation and oxidative stress in livers of C57BL/6-mice, which in addition showed increased weight gain and insulin resistance, thus displaying a phenotype closely resembling all clinical features of NASH in patients with metabolic syndrome. In striking contrast, a soybean oil-containing Western-type diet without cholesterol (SOD) induced only mild steatosis but not hepatic inflammation, fibrosis, weight gain or insulin resistance. Another high-fat diet, mainly consisting of lard and supplemented with fructose in drinking water (LAD + Fru), resulted in more prominent weight gain, insulin resistance and hepatic steatosis than SOD + Cho, but livers were devoid of inflammation and fibrosis. Although both LAD + Fru-and SOD + Cho-fed animals had high plasma cholesterol, liver cholesterol was elevated only in SOD + Cho animals. Cholesterol induced expression of chemotactic and inflammatory cytokines in cultured Kupffer cells and rendered hepatocytes more susceptible to apoptosis. In summary, dietary cholesterol in the SOD + Cho diet may trigger hepatic inflammation and fibrosis. SOD + Cho-fed animals may be a useful disease model displaying many clinical features of patients with the metabolic syndrome and NASH.
Glycoproteins adsorbing on an implant upon contact with body fluids can affect the biological response in vitro and in vivo, depending on the type and conformation of the adsorbed biomacromolecules. However, this process is poorly characterized and so far not controllable. Here, protein monolayers of high molecular cohesion with defined density are transferred onto polymeric substrates by the Langmuir-Schaefer (LS) technique and were compared with solution deposition (SO) method. It is hypothesized that on polydimethylsiloxane (PDMS), a substrate with poor cell adhesion capacity, the fibronectin (FN) layers generated by the LS and SO methods will differ in their organization, subsequently facilitating differential stem cell adhesion behavior. Indeed, atomic force microscopy visualization and immunofluorescence images indicated that organization of the FN layer immobilized on PDMS was uniform and homogeneous. In contrast, FN deposited by SO method was rather heterogeneous with appearance of structures resembling protein aggregates. Human mesenchymal stem cells showed reduced absolute numbers of adherent cells, and the vinculin expression seemed to be higher and more homogenously distributed after seeding on PDMS equipped with FN by LS in comparison with PDMS equipped with FN by SO. These divergent responses could be attributed to differences in the availability of adhesion molecule ligands such as the Arg-Gly-Asp (RGD) peptide sequence presented at the interface. The LS method allows to control the protein layer characteristics, including the thickness and the protein orientation or conformation, which can be harnessed to direct stem cell responses to defined outcomes, including migration and differentiation. Copyright (c) 2016 John Wiley & Sons, Ltd.
A series of multiblock copolymers (PDLCL) synthesized from oligo(omega-pentadecalactone) diol (OPDL) and oligo(epsilon-caprolactone) diol (OCL), which are linked by 2,2(4), 4-trimethyl-hexamethylene diisocyanate (TMDI), is investigated by the Langmuir monolayer technique at the air-water interface. Brewster angle microscopy (BAM) and spectroscopic ellipsometry are employed to characterize the polymer film morphologies in situ. PDLCL containing >= 40 wt% OCL segments form homogeneous Langmuir monofilms after spreading. The film elasticity modulus decreases with increasing amounts of OPDL segments in the copolymer. In contrast, the OCL-free polyesterurethane OPDL-TMDI cannot be spread to monomolecular films on the water surface properly, and movable slabs are observed by BAM even at low surface pressures. The results of the in situ morphological characterization clearly show that essential information concerning the reliability of Langmuir monolayer degradation (LMD) experiments cannot be obtained from the evaluation of the pi-A isotherms only. Consequently, in situ morphological characterization turns out to be indispensable for characterization of Langmuir layers before LMD experiments.
Three oligo[(rac-lactide)-co-glycolide] based polyesterurethanes (OLGA-PUs) containing different diurethane linkers are investigated by the Langmuir monolayer technique and compared to poly[(rac-lactide)-co-glycolide] (PLGA) to elucidate the influence of the diurethane junction units on hydrophilicity and packing motifs of these polymers at the air-water interface. The presence of diurethane linkers does not manifest itself in the Langmuir layer behavior both in compression and expansion experiments when monomolecular films of OLGA-PUs are spread on the water surface. However, the linker retard the evolution of morphological structures at intermediate compression level under isobaric conditions (with a surface pressure greater than 11 mN m(-1)) compared to the PLGA, independent on the chemical structure of the diurethane moiety. The layer thicknesses of both OLGA-PU and PLGA films decrease in the high compression state with decreasing surface pressure, as deduced from ellipsometric data. All films must be described with the effective medium approximation as water swollen layers.