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Sphingolipids are characterized by a broad range of bioactive properties. Particularly, the development of insulin resistance, a major pathophysiological hallmark of Type 2 Diabetes mellitus (T2D), has been linked to ceramide signaling. Since vitamin D supplementation may slow down T2D progression by improving glucose concentrations and insulin sensitivity, we investigated whether vitamin D supplementation impacts on plasma sphingolipid levels in T2D patients. Thus, plasma samples of 59 patients with non-insulin-requiring T2D from a placebo-controlled, randomized, and double-blind study were retrospectively analyzed. Once per week, patients received either 20 drops of Vigantol oil, corresponding to a daily dose of 1904 IU/d vitamin D (verum: n = 31), or a placebo oil consisting of medium chain triglycerides (placebo: n = 28). Blood samples were taken from all of the participants at three different time points: 1) at the beginning of the study (baseline), 2) after 6 months supplementation, and 3) after an additional 6 months of follow-up. Plasma sphingolipids were measured by high-performance liquid chromatography tandem mass spectrometry. At baseline and 6 months follow-up, no significant differences in plasma sphingolipid species were detected between the placebo and verum groups. After 6 months, vitamin D supplementation significantly enhanced plasma C18dihydroceramide (dhCer; N-stearoyl-sphinganine (d18:0/18:0)) and C18ceramide (Cer; N-stearoyl-sphingosine (d18:1/18:0)) levels were observed in the verum group compared to the placebo group. This was accompanied by significantly higher 25-hydroxyvitamin D3 (25(OH)D3) blood levels in patients receiving vitamin D compared to the placebo group. Taken together, vitamin D supplementation induced changes of the C18 chain-length-specific dhCer and Cer plasma levels in patients with T2D. The regulation of sphingolipid signaling by vitamin D may thus unravel a novel mechanism by which vitamin D can influence glucose utilization and insulin action. Whether this acts favorably or unfavorably for the progression of T2D needs to be clarified.
Visualization of cytosolic ribosomes on the surface of mitochondria by electron cryo‐tomography
(2017)
We employed electron cryo‐tomography to visualize cytosolic ribosomes on the surface of mitochondria. Translation‐arrested ribosomes reveal the clustered organization of the TOM complex, corroborating earlier reports of localized translation. Ribosomes are shown to interact specifically with the TOM complex, and nascent chain binding is crucial for ribosome recruitment and stabilization. Ribosomes are bound to the membrane in discrete clusters, often in the vicinity of the crista junctions. This interaction highlights how protein synthesis may be coupled with transport. Our work provides unique insights into the spatial organization of cytosolic ribosomes on mitochondria.
Yves R. Simon (1903-1961), one of the greatest contemporary philosophers, gives a modern formulation for many classical philosophical concepts such as authority, the common good, and natural law. These topics have received extensive attention from scholars. Simon also discusses the nature of human virtue, moral and intellectual, but this topic has been less studied until now. The idea of virtue, and in our case virtue in political life, runs through Simon's works. Through a close study of Simon's works and the relevant secondary literature, this book explores Simon's definition of virtue in order to highlight its originality, and show how he weaves the need for it into the fabric of three facets of political life, namely, the common good, the virtue of the ruler and the ruled, and the law. These ideas are important for the ruler-ship of any country and especially of developing nations which are populated by sit-tight dictators. Philosophy can be dry and abstract, yet in this case we deal with one of its more practical manifestations.
Der Aufbau unserer Umwelt folgt bestimmten Regelmäßigkeiten, die für uns so selbstverständlich sind, dass wir ihrer kaum bewusst sind. Doch würden Sie die Milch unter dem Bett suchen oder das Kissen in der Badewanne? Wohl kaum. Die Psychologin Prof. Melissa Lê-Hoa Võ untersucht das erlernte Regelwerk, die Entwicklung von sogenanntem Szenenwissen, mithilfe psychophysischer Verfahren, Blickbewegungsund Hirnpotenzialmessungen.