Role of Interaction and Nucleoside Diphosphate Kinase B in Regulation of the Cystic Fibrosis Transmembrane Conductance Regulator Function by cAMP-Dependent Protein Kinase A

Cystic fibrosis results from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent protein kinase A (PKA) and ATP-regulated chloride channel. Here, we demonstrate that nucleoside diphosphate kinase B (NDPK-B, NM23-H2) forms a functional complex with CFTR. In airway epithelia forskolin/IBMX significantly increases NDPK-B co-localisation with CFTR whereas PKA inhibitors attenuate complex formation. Furthermore, an NDPK-B derived peptide (but not its NDPK-A equivalent) disrupts the NDPK-B/CFTR complex in vitro (19-mers comprising amino acids 36-54 from NDPK-B or NDPK-A). Overlay (Far-Western) and Surface Plasmon Resonance (SPR) analysis both demonstrate that NDPK-B binds CFTR within its first nucleotide binding domain (NBD1, CFTR amino acids 351-727). Analysis of chloride currents reflective of CFTR or outwardly rectifying chloride channels (ORCC, DIDS-sensitive) showed that the 19-mer NDPK-B peptide (but not its NDPK-A equivalent) reduced both chloride conductances. Additionally, the NDPK-B (but not NDPK-A) peptide also attenuated acetylcholine-induced intestinal short circuit currents. In silico analysis of the NBD1/NDPK-B complex reveals an extended interaction surface between the two proteins. This binding zone is also target of the 19-mer NDPK-B peptide, thus confirming its capability to disrupt NDPK-B/CFTR complex. We propose that NDPK-B forms part of the complex that controls chloride currents in epithelia

NM23 proteins: innocent bystanders or local energy boosters for CFTR?

NM23 proteins NDPK-A and -B bind to the cystic fibrosis (CF) protein CFTR in different ways from kinases such as PKA, CK2 and AMPK or linkers to cell calcium such as calmodulin and annexins. NDPK-A (not -B) interacts with CFTR through reciprocal AMPK binding/control, whereas NDPK-B (not -A) binds directly to CFTR. NDPK-B can activate G proteins without ligand-receptor coupling, so perhaps NDPK-B's binding influences energy supply local to a nucleotide-binding site (NBD1) needed for CFTR to function. Curiously, CFTR (ABC-C7) is a member of the ATP-binding cassette (ABC) protein family that does not obey 'clan rules'; CFTR channels anions and is not a pump, regulates disparate processes, is itself regulated by multiple means and is so pleiotropic that it acts as a hub that orchestrates calcium signaling through its consorts such as calmodulin/annexins. Furthermore, its multiple partners make CFTR dance to different tunes in different cellular and subcellular locations as it recycles from the plasma membrane to endosomes. CFTR function in airway apical membranes is inhibited by smoking which has been dubbed 'acquired CF'. CFTR alone among family members possesses a trap for other proteins that it unfurls as a 'fish-net' and which bears consensus phosphorylation sites for many protein kinases, with PKA being the most canonical. Recently, the site of CFTR's commonest mutation has been proposed as a knock-in mutant that alters allosteric control of kinase CK2 by log orders of activity towards calmodulin and other substrates after CFTR fragmentation. This link from CK2 to calmodulin that binds the R region invokes molecular paths that control lumen formation, which is incomplete in the tracheas of some CF-affected babies. Thus, we are poised to understand the many roles of NDPK-A and -B in CFTR function and, especially lumen formation, which is defective in the gut and lungs of many CF babies

Influence of dehydration on strength of silica fibers

International audienceStrength and dynamic fatigue behaviour of silica optical fibers has been measured in very dry atmosphere. Bare and coated fibers were compared to characterize the influence of the polymer. The stress corrosion susceptibility parameter has been evaluated. Subcritical crack growth effect was found to be different in coated and bare fibers while their strength was found to be close. The strength measurement have been done using a two-point bending set up

A new tool for advanced vehicle simulations

7th International Conference on Engines for Automobile ICE 2005, CAPRI, ITALIE, 11-/09/2005 - 16/09/2005To overcome future stringent regulations on pollutant emissions and to decrease CO emissions and fuel consumption, hybrid vehicles seem to be one of the near future most promising technologies. This type of car uses complex energy management and control strategy. Simulation can be very useful for the development of such a control system. This paper highlights a new library developed under the AMESim software that enables the simulation of complex interactive systems in vehicles. In addition, the possibility to combine with other AMESim modules, allows the users to add more complexity to any of the sub-components of the vehicle. As an illustration of this new tool capability, we propose in this paper a simulation example of the Prius, the most known hybrid vehicle which was the first commercial vehicle in 1997 and selected as the 2004 Car of the Year in Europe. Comparisons between measurements and simulations of the response of different components are presented on different driving cycles

Guest Editorial Focused Section on Modeling and Control of Soft Manipulators

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Mechanical Strength of Stripped Optical Fiber

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Modeling of Continuum Manipulators using Pythagorean Hodograph Curves

International audienceResearch on continuum manipulators is increasingly developing in the context of bionic robotics because of their many advantages over conventional rigid manipulators. Due to their soft structure, they have inherent flexibility which makes it a huge challenge to control them with high performances. Before elaborating a control strategy of such robots, it is essential to reconstruct first the behavior of the robot through the development of an approximate behavioral model. This can be kinematic or dynamic depending on the conditions of operation of the robot itself. Kinematically, two types of modeling methods exist to describe the robot behavior, quantitative methods describe a model-based method; and qualitative methods, describe a learning-based method. In kinematic modeling of continuum manipulator, the assumption of constant curvature is often considered to simplify the model formulation. In this work, a quantitative modeling method is proposed, based on the Pythagorean Hodograph (PH) curves. The aim is to obtain a 3D reconstruction of the shape of the continuum manipulator with variable curvature, allowing the calculation of its inverse kinematic model. It is noticed that the performances of the PH-based kinematic modeling of continuum manipulators are considerable regarding position accuracy, shape reconstruction and time-cost of the model calculation, than other kinematic modeling methods, for two cases: free load manipulation and variable load manipulation. This modeling method is applied to Compact Bionic Handling Assistant (CBHA) manipulator for validation. The results are compared with other inverse kinematic models developed in case of CBHA manipulator

Characterisation of the hygro-thermo-mechanical behaviour of organic matrix composites instrumented with optical fibres: A study of interfacial bonding

International audienceMoisture diffusion can decrease the mechanical stiffness and strength of organic matrix composites. Recently, Fibre Bragg Grating (FBG) sensors have been used in order to study the hygroscopic ageing of polyester/glass composites at room temperature. In the present study, the hygroscopic strain measurement of polyester/glass composite has been achieved at room temperature. Furthermore, measurements have been done at higher temperatures in order to better understand the combination of both hygroscopic ageing and varying temperatures on the mechanical properties of these composite samples. The Bragg wavelength (λbλb) was found to shift linearly over a temperature range from room temperature to 35 °C. Beyond 35 °C, the Bragg wavelength does not linearly vary as a function of the temperature. A strong variation of the Bragg wavelength above a specific temperature threshold was found. This could be explained according to two mechanisms. Firstly, hygroscopic ageing could result in a decrease of the glass transition temperature (Tg) of the polymer matrix. Therefore viscoelastic behavior may appear beyond this temperature. Hygroscopic ageing could also degrade the interfacial shear strength between the fibre and the resin. Differential Scanning Calorimetry (DSC) analyses showed that hygroscopic aging does not affect the Tg of the polyester resin. Furthermore, it has been found that the hygroscopic aging degrades the interfacial adhesion of the optical fibre/polyester according to the considerable decreases of the interfacial shear strength observed in practic