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Background: Despite the beneficial effects of type 4 dipeptidyl peptidase (DPP-4) inhibitors on glucose levels, its effects on diabetic nephropathy remain unclear.
Method: This study examined the long-term renoprotective effects of DPP-4 inhibitor linagliptin in db/db mice, a model of type 2 diabetes.
Results were compared with the known beneficial effects of renin-angiotensin system blockade by enalapril. Ten-week-old male diabetic db/db mice were treated for 3 months with either vehicle (n = 10), 3 mg linagliptin/kg per day (n = 8), or 20 mg enalapril/kg per day (n = 10). Heterozygous db/m mice treated with vehicle served as healthy controls (n = 8). Results: Neither linagliptin nor enalapril had significant effects on the parameters of glucose metabolism or blood pressure in diabetic db/db mice. However, linagliptin treatment reduced albuminuria and attenuated kidney injury. In addition, expression of podocyte marker podocalyxin was normalized. We also analysed DPP-4 expression by immunofluorescence in human kidney biopsies and detected upregulation of DPP-4 in the glomeruli of patients with diabetic nephropathy, suggesting that our findings might be of relevance for human kidney disease as well.
Conclusion: Treatment with DPP-4 inhibitor linagliptin delays the progression of diabetic nephropathy damage in a glucose-independent and blood-pressure-independent manner. The observed effects may be because of the attenuation of podocyte injury and inhibition of myofibroblast transformation.
Membranes of eukaryotic cells contain high lipid-order sterol-rich domains that are thought to mediate temporal and spatial organization of cellular processes. Sterols are crucial for execution of cytokinesis, the last stage of cell division, in diverse eukaryotes. The cell plate of higher-plant cells is the membrane structure that separates daughter cells during somatic cytokinesis. Cell-plate formation in Arabidopsis relies on sterol- and DYNAMIN-RELATED PROTEIN1A (DRP1A)-dependent endocytosis. However, functional relationships between lipid membrane order or lipid packing and endocytic machinery components during eukaryotic cytokinesis have not been elucidated. Using ratiometric live imaging of lipid order-sensitive fluorescent probes, we show that the cell plate of Arabidopsis thaliana represents a dynamic, high lipid-order membrane domain. The cell-plate lipid order was found to be sensitive to pharmacological and genetic alterations of sterol composition. Sterols co-localize with DRP1A at the cell plate, and DRP1A accumulates in detergent-resistant membrane fractions. Modifications of sterol concentration or composition reduce cell-plate membrane order and affect DRP1A localization. Strikingly, DRP1A function itself is essential for high lipid order at the cell plate. Our findings provide evidence that the cell plate represents a high lipid-order domain, and pave the way to explore potential feedback between lipid order and function of dynamin-related proteins during cytokinesis.
We present pollen-based reconstructions of the spatio-temporal dynamics of northern European regional vegetation abundance through the Holocene. We apply the Regional Estimates of VEgetation Abundance from Large Sites (REVEALS) model using fossil pollen records from eighteen sites within five modern biomes in the region. The eighteen sites are classified into four time-trajectory types on the basis of principal components analysis of both the REVEALS-based vegetation estimates (RVs) and the pollen percentage (PPs). The four trajectory types are more clearly separated for RVs than PPs. Further, the timing of major Holocene shifts, rates of compositional change, and diversity indices (turnover and evenness) differ between RVs and PPs. The differences are due to the reduction by REVEALS of biases in fossil pollen assemblages caused by different basin size, and inter-taxonomic differences in pollen productivity and dispersal properties. For example, in comparison to the PPs, the RVs show an earlier increase in Corylus and Ulmus in the early-Holocene and a more pronounced increase in grassland and deforested areas since the mid-Holocene. The results suggest that the influence of deforestation and agricultural activities on plant composition and abundance from Neolithic times was stronger than previously inferred from PPs. Relative to PPs, RVs show a more rapid compositional change, a largest decrease in turnover, and less variable evenness in most of northern Europe since 5200 cal yr BP. All these changes are primarily related to the strong impact of human activities on the vegetation. This study demonstrates that RV-based estimates of diversity indices, timing of shifts, and rates of change in reconstructed vegetation provide new insights into the timing and magnitude of major human distribution on Holocene regional, vegetation, feature that are critical in the assessment of human impact on vegetation, land-cover, biodiversity, and climate in the past.
Two experiments examined the effects of dispositional optimism and attributions on feelings of success in a performance setting. In Experiment 1, participants successfully solved three cognitive tasks and attributed the success either internally (i.e., to themselves) or externally (i.e., to a teammate). We found no effect of optimism, but a significant effect of the attribution: Internal attribution predicted an increase in feelings of success. In Experiment 2, we replicated the design and adopted an extreme groups approach in order to include the extremes of the optimism dimension. Only optimism affected feelings of success in this sample: Pessimistic participants showed higher increases in feelings of success than optimistic participants. We conclude that optimism, if disentangled from attribution, may have an effect on affect, with pessimism showing potential affective benefits. However, this association may be concealed if samples with a restricted range of the optimism dimension are studied.
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
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