Organogels based on edible oils and specific mixtures of phytosterols can serve as structured systems with a low saturated fat content. These low-SAFA organogels can be used also to create o/w emulsions. Little is known about the structures formed in these specific organogels and at the emulsion interface. We studied o/w organogels on different length scales to describe and understand their micro-structural features. Very basic processing conditions such as composition, temperature and storage time were taken into account. Two different types of structure were observed; at the smallest scale, long thin crystals are formed out of the oil phase into the continuous water phase. We propose that these are needle-like crystals. Next, tube-like structures are identified and can be visualized as tubular micelles. A model is proposed which fits the dimension (*7 nm) with the length scale of the molecular building blocks (TAGs and sterols). As edible fats from food products are enzymatically hydrolyzed in the gut prior to absorption, we also looked into the impact on the lipase reaction speed. Simple in vitro enzymatic hydrolysis experiments showed a slower enzymatic digestion. Organogel systems and emulsion made thereof have interesting food structuring properties with possible advantages in composition (low SAFA) and digestion speed.

Original research article BACKGROUND: L-type calcium channels (LTCCs) play important roles in regulating cardiomyocyte physiology, which is governed by appropriate LTCC trafficking to and density at the cell surface. Factors influencing the expression, half-life, subcellular trafficking, and gating of LTCCs are therefore critically involved in conditions of cardiac physiology and disease. METHODS:Yeast 2-hybrid screenings, biochemical and molecular evaluations, protein interaction assays, fluorescence microscopy, structural molecular modeling, and functional studies were used to investigate the molecular mechanisms through which the LTCC Ca v β2 chaperone regulates channel density at the plasma membrane. RESULTS:On the basis of our previous results, we found a direct linear correlation between the total amount of the LTCC pore-forming Ca v α1.2 and the Akt-dependent phosphorylation status of Ca v β2 both in a mouse model of diabetic cardiac disease and in 6 diabetic and 7 nondiabetic cardiomyopathy patients with aortic stenosis undergoing aortic valve replacement. Mechanistically, we demonstrate that a conformational change in Ca v β2 triggered by Akt phosphorylation increases LTCC density at the cardiac plasma membrane, and thus the inward calcium current, through a complex pathway involving reduction of Ca v α1.2 retrograde trafficking and protein degradation through the prevention of dynaminmediated LTCC endocytosis; promotion of Ca v α1.2 anterograde trafficking by blocking Kir/Gem-dependent sequestration of Ca v β2, thus facilitating the chaperoning of Ca v α1.2; and promotion of Ca v α1.2 transcription by the prevention of Kir/Gem-mediated shuttling of Ca v β2 to the nucleus, where it limits the transcription of Ca v α1.2 through recruitment of the heterochromatin protein 1γ epigenetic repressor to the Cacna1c promoter. On the basis of this mechanism, we developed a novel mimetic peptide that, through targeting of Ca v β2, corrects LTCC lifecycle alterations, facilitating the proper function of cardiac cells. Delivery of mimetic peptide into a mouse model of diabetic cardiac disease associated with LTCC abnormalities restored impaired calcium balance and recovered cardiac function. CONCLUSIONS:We have uncovered novel mechanisms modulating LTCC trafficking and life cycle and provide proof of concept for the use of Ca v β2 mimetic peptide as a novel therapeutic tool for the improvement of cardiac conditions correlated with alterations in LTCC levels and function.Peptidomimetic targeting of ca v β2 Overcomes Dysregulation of the l-type calcium channel Density and recovers cardiac Function

Voltage-gated Ca2+ channels are involved in numerous physiological functions and various mechanisms finely tune their activity, including the Ca2+ ion itself. This is well exemplified by the Ca2+-dependent inactivation of L-type Ca2+ channels, whose alteration contributes to the dramatic disease Timothy Syndrome. For T-type Ca2+ channels, a long-held view is that they are not regulated by intracellular Ca2+. Here we challenge this notion by using dedicated electrophysiological protocols on both native and expressed T-type Ca2+ channels. We demonstrate that a rise in submembrane Ca2+ induces a large decrease in T-type current amplitude due to a hyperpolarizing shift in the steady-state inactivation. Activation of most representative Ca2+-permeable ionotropic receptors similarly regulate T-type current properties. Altogether, our data clearly establish that Ca2+ entry exerts a feedback control on T-type channel activity, by modulating the channel availability, a mechanism that critically links cellular properties of T-type Ca2+ channels to their physiological roles.DOI: http://dx.doi.org/10.7554/eLife.22331.001