Effect of diaminopropionic acid (Dap) on the biophysical properties of a modified synthetic channel-forming peptide

Citation: Bukovnik, U., Sala-Rabanal, M., Francis, S., Frazier, S. J., Schultz, B. D., Nichols, C. G., & Tomich, J. M. (2013). Effect of diaminopropionic acid (Dap) on the biophysical properties of a modified synthetic achannel-forming peptide. Molecular Pharmaceutics, 10(10), 3959-3966.Channel replacement therapy, based on synthetic channel-forming peptides (CFPs) with the ability to supersede defective endogenous ion channels, is a novel treatment modality that may augment existing interventions against multiple diseases. Previously, we derived CFPs from the second transmembrane segment of the α-subunit of the glycine receptor, M2GlyR, which forms chloride-selective channels in its native form. The best candidate, NK₄-M2GlyR T19R, S22W (p22-T19R, S22W), was water-soluble, incorporated into cell membranes and was nonimmunogenic, but lacked the structural properties for high conductance and anion selectivity when assembled into a pore. Further studies suggested that the threonine residues at positions 13, 17, and 20 line the pore of assembled p22-T19R, S22W, and here we used 2,3-diaminopropionic acid (Dap) substitutions to introduce positive charges to the pore-lining interface of the predicted p22-T19R, S22W channel. Dap-substituted p22-T19R, S22W peptides retained the α-helical secondary structure characteristic of their parent peptide, and induced short-circuit transepithelial currents when exposed to the apical membrane of Madin-Darby canine kidney (MDCK) cells; the sequences containing multiple Dap-substituted residues induced larger currents than the peptides with single or no Dap substitutions. To gain further insights into the effects of Dap residues on the properties of the putative pore, we performed two-electrode voltage clamp electrophysiology on Xenopus oocytes exposed to p22-T19R, S22W or its Dap-modified analogues. We observed that Dap-substituted peptides also induced significantly larger voltage-dependent currents than the parent compound, but there was no apparent change in reversal potential upon replacement of external Na⁺, Cl⁻ or K⁺, indicating that these currents remained nonselective. These results suggest that the introduction of positively charged side chains in predicted pore-lining residues does not improve anion-to-cation selectivity, but results in higher conductance, perhaps due to higher oligomerization numbers

Uncooled micro-earth sensor for micro-satellite attitude control: Earth remote sensing application

International audienceMEMS technology now makes possible to produce active microdevices combining detection, signal processing, and data storage with accuracy and compactness. In view of their characteristics, it can be expected that such microsensors will be used extensively in space applications dedicated to micro and nano satellites.For this purpose, a specific investigation dealing with the complete development of a micro-earth sensor used for attitude control of Low Earth Orbit satellites is under realization and test. Based on an infrared uncooled 320x240 microbolometer the experimental characterization of the final active system consists of three microsensors linear arrays of 240 pixels of the same technology, radialy spaced at 120°, watching and receiving earth IR radiations. The transition between excited and non excited pixels will determine the IR image of the Earth/Space transition hidden in IR atmosphere response. Specific on-chip algorithms have been implemented to extract the transition and compute the attitude satellite position in roll and pitch.The complete physical system modeling of one linear 240 pixels array including earth models, optic characteristics, microbolometer behavioral models, mixed analog/digital electronics and associated algorithms is consistent (at ±8% ) with the breadboard measurements

La draperie en Normandie du XIIIe siècle au XXe siècle

Né des rencontres suscitées par les euroconférences de 2001 et 2002 consacrées à l'histoire de la laine, cet ouvrage réunit une quinzaine de contributions de chercheurs normands mais aussi parisiens et étrangers. De l'époque médiévale à la particularisation actuelle, en passant par l'apogée des xviiie et xixe siècles, les auteurs analysent la production des différents centres normands, les réseaux de commercialisation et d'exportation, les mécanismes des transferts de technologie. Se recoupant et se répondant les unes aux autres, ces études éclairent l'histoire de l'une des principales activités industrielles de la région

The effect of cooking on phytochemical content in vegetables: a review

Cooking induces many chemical and physical modifications in foods; among these the phytochemical content can change. Many authors have studied variations in vegetable nutrients after cooking, and great variability in the data has been reported. In this review more than 100 articles from indexed scientific journals were considered in order to assess the effect of cooking on different phytochemical classes. Changes in phytochemicals upon cooking may result from two opposite phenomena: (1) thermal degradation, which reduces their concentration, and (2) a matrix softening effect, which increases the extractability of phytochemicals, resulting in a higher concentration with respect to the raw material. The final effect of cooking on phytochemical concentration depends on the processing parameters, the structure of food matrix, and the chemical nature of the specific compound. Looking at the different cooking procedures it can be concluded that steaming will ensure better preservation/extraction yield of phenols and glucosinolates than do other cooking methods: steamed tissues are not in direct contact with the cookingmaterial (water or oil) so leaching of soluble compounds into water isminimised and, at the same time, thermal degradation is limited. Carotenoids showed a different behaviour; a positive effect on extraction and the solubilisation of carotenes were reported after severe processing