Pflügers Archiv : European journal of physiology, 2003
Ca(2+) signalling is one of the most important means in mammalian cells of relaying the action of... more Ca(2+) signalling is one of the most important means in mammalian cells of relaying the action of hormones and neurotransmitters. The great diversity of agonist-induced Ca(2+) signatures, visualized by optical imaging techniques, can be explained by the production of intracellular messengers triggering Ca(2+) release from internal stores and/or by different coupling of Ca(2+) release to Ca(2+) entry. Several messengers, such as inositol trisphosphate and cyclic ADP-ribose, have been identified to date. More recent studies have reported the important role of a newly discovered Ca(2+) releasing messenger, nicotinic acid adenine dinucleotide phosphate (NAADP). These studies have shown important interactions of these messengers in the generation of specific Ca(2+) signals. NAADP acts at a very low concentration and seems to have a key role in sensitising cyclic ADP-ribose and inositol trisphosphate receptors. These points will be discussed in the present review.
Many physiological processes are controlled by a great diversity of Ca2+ signals. Within cell, Ca... more Many physiological processes are controlled by a great diversity of Ca2+ signals. Within cell, Ca2+ signals depend upon Ca2+ entry and/or Ca2+ release from internal Ca2+ stores. The control of Ca2+-store mobilization is ensured by a family of messengers comprising inositol 1,4,5 trisphosphate, cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate (NAADP). From recent works, new concepts have emerged where activation of the cells by outside stimuli, acting at the plasma membrane, results in the synthesis of multiple Ca2+-releasing messengers which may interact and shape complex Ca2+ signals in the cytosol as well as in the nucleus. This contribution will cover the most recent advances on NAADP signalling with some emphasis on neurons.
Synchrotron radiation X-ray scattering experiments were performed on unmyelinated pike olfactory ... more Synchrotron radiation X-ray scattering experiments were performed on unmyelinated pike olfactory nerves. The difference between the meridional and the equatorial traces of the 2-D spectra yielded the 1-D equatorial intensity of the macromolecular components oriented with respect to the nerve: axonal membranes, microtubules and other cytoskeletal filaments. These 1-D spectra display a diffuse band typical of bilayer membranes and, at small s, a few sharper bands reminiscent of microtubules. All the spectra merge at large s. The intensity of the axonal membrane was determined via a noise analysis of the nerve-dependent spectra, involving also the notion that the thickness of the membrane is finite. The shape of the intensity function indicated that the electron density profile is not centrosymmetric. The knowledge of intensity and thickness paved the way to the electron density profile via an ab initio solution of the phase problem. An iterative procedure was adopted: (i) choose the lattice D of a 1-D pseudo crystal, interpolate the intensity at the points sh = h/D, adopt an arbitrary set of initial phases and compute the profile; (ii) determine the phases corresponding to this profile truncated by the thickness D/2; (iii) repeat the operation with the updated phases until a stable result is obtained. This iterative procedure was carried out for different D-values, starting in each case from randomly generated phases: stable results were obtained in less than 10,000 iterations. Most importantly, for D in the vicinity of 200 A, the overwhelming majority of the profiles were congruent with each other. These profiles were strongly asymmetric and otherwise typical of biological membranes.
The effects of several agents, sugars, isotonic KCl, and a variety of drugs, on the structure of ... more The effects of several agents, sugars, isotonic KCl, and a variety of drugs, on the structure of the axonal membranes of unmyelinated pike olfactory nerve have been studied by synchrotron radiation X-ray scattering experiments. The main effects of the sugars are: (i) to increase the electron density of the extra-axonal space and thereby yield the absolute scale of the electron density profile; (ii) to osmotically stress the membrane and thus yield its elastic modulus of area compressibility, since the related strain, thickness dilation, is directly determined by the X-ray scattering experiments. Exposure to isotonic KCl, a depolarizing agent, induces membrane thickness to increase. The energy liberated in this process is a function of the amplitude of the dilation and of the elastic modulus of the membrane. This energy turns out to be close to the thermal energy liberated by the pike olfactory nerve during the initial phase of action potential that has previously been measured by others. Electrical depolarization thus seems to be accompanied by a thickness dilation of the axonal membrane. Another effect of isotonic KCl is to induce a large fraction of the membranes to pair by tight apposition of their extra-axonal faces. Local anaesthetics and some drugs have the effect of altering membrane thickness. All these observations are interpreted in terms of a modulation of the conformational disorder of the hydrocarbon chains of the lipid molecules.
An unusual inward current which is slowly elicited in the Xenopus oocyte membrane during sustaine... more An unusual inward current which is slowly elicited in the Xenopus oocyte membrane during sustained depolarization is reportedly carried by Na+. It is thought that Na+ selective channels are in some way induced to become voltage-sensitive by the depolarization. Earlier studies report that the induction process involves a phospholipase C and a protein kinase C as well as calcium ions. The present work investigated the origins of this calcium in the oocyte. We show that injection of the powerful Ca2+ chelator (BAPTA) in the oocyte, before induction of the Na+ channels, prevented the appearance of the Na+ current, confirming an important role for [Ca2+]i. However, in oocytes perfused with Ca2+ -free medium, induction of the channels could still be obtained, indicating that induction did not depend upon the entry of external Ca2+. Downmodulation of Ca2+ release from inositol 1,4,5-trisphosphate (InsP3)-sensitive stores with caffeine and with a low molecular weight heparin resulted in decreased or no Na+ currents. The results are discussed in terms of the contributions from other endogenous calcium-dependent conductances which can influence the Na+ current amplitudes and time courses. The results presented support the idea that intracellular Ca2+ increase principally due to Ca2+ released from InsP3-sensitive stores is needed by the enzyme systems to produce the depolarization-induced activation of the Na+ conductance in the Xenopus oocyte.
2010 Fifth IEEE International Symposium on Electronic Design, Test & Applications, 2010
Abstract A flexible hardware accelerator for full-search vector quantization (VQ) has been develo... more Abstract A flexible hardware accelerator for full-search vector quantization (VQ) has been developed as a component for a system on a programmable chip (SoPC) to use in real-time image compression and recognition applications. In the system, the number of elements ...
ABSTRACT Objectif DIABEO est un système de télémédecine utilisant un logiciel de carnet électroni... more ABSTRACT Objectif DIABEO est un système de télémédecine utilisant un logiciel de carnet électronique, téléchargé sur un PDA-phone, et couplé à une aide à la décision des doses d’insuline et à la possibilité de téléconsultations avec l’ensemble des données accessibles aux soignants via Internet. L’objectif de cette étude était d’évaluer l’efficacité de ce système à améliorer l’équilibre glycémique de patients diabétiques de type 1 (DT1) chroniquement mal équilibrés. Patients et Méthodes 180 adultes DT1 (> 1 an), traités par basal-bolus (> 6 mois, par pompe ou multi-injections) et avec une HbA1c > 8 % à au moins 2 reprises consécutives, ont été randomisés en 3 groupes, pendant 6 mois : contrôle avec suivi habituel par consultations trimestrielles (G1), DIABEO avec consultations trimestrielles (G2) et DIABEO couplé à des consultations téléphoniques tous les 15 j et sans consultation face-face (G3). Résultats A 6 mois, l’HbA1c est significativement plus basse dans les G2 (8,6 %, p = 0,022) et G3 (8,4%, p < 0,002) en comparaison du G1 (9,1 %). L’évolution de l’HbA1c entre 0 et 6 mois est également significativement meilleure (p < 0,001) pour les G2 (-0,5 %) et G3 (-0,7 %), en comparaison du G1 (+0,2 %, NS). Le pourcentage de patients atteignant un taux d’HbA1c < 7,5 % est plus élevé dans le G3 (19 %) que dans le G2 (8 %, NS) et G1 (3 %, p = 0,007). Le nombre d’hypoglycémies bénignes ou sévères n’est pas différent entre les 3 groupes. Le temps moyen cumulé de consultation sur 6 mois est de 1,2 h dans chaque groupe tandis que le temps total de prise en charge (incluant déplacement et attente des patients) est moindre dans le G3 (1,2 h, p < 0,001) que dans les G1 (7,1 h) et G2 (8,3 h). 66 % des patients du G2 et 75 % de ceux du G3 souhaitaient poursuivre l’utilisation de DIABEO. Conclusion Le système DIABEO permet d’améliorer significativement, à 6 mois, l’HbA1c de patients DT1 mal équilibrés, sans augmentation du risque hypoglycémique. De plus, associé aux consultations téléphoniques, il permet à un nombre plus élevé de patients d’atteindre un très bon contrôle glycémique, avec une meilleure efficience médicale et un gain de temps pour les patients. Une large majorité des patients souhaitent poursuivre l’utilisation au long cours de ce système, désormais en libre accès, pour patients et diabéto, via « Diabeo.com ».
Pflügers Archiv : European journal of physiology, 2003
Ca(2+) signalling is one of the most important means in mammalian cells of relaying the action of... more Ca(2+) signalling is one of the most important means in mammalian cells of relaying the action of hormones and neurotransmitters. The great diversity of agonist-induced Ca(2+) signatures, visualized by optical imaging techniques, can be explained by the production of intracellular messengers triggering Ca(2+) release from internal stores and/or by different coupling of Ca(2+) release to Ca(2+) entry. Several messengers, such as inositol trisphosphate and cyclic ADP-ribose, have been identified to date. More recent studies have reported the important role of a newly discovered Ca(2+) releasing messenger, nicotinic acid adenine dinucleotide phosphate (NAADP). These studies have shown important interactions of these messengers in the generation of specific Ca(2+) signals. NAADP acts at a very low concentration and seems to have a key role in sensitising cyclic ADP-ribose and inositol trisphosphate receptors. These points will be discussed in the present review.
Many physiological processes are controlled by a great diversity of Ca2+ signals. Within cell, Ca... more Many physiological processes are controlled by a great diversity of Ca2+ signals. Within cell, Ca2+ signals depend upon Ca2+ entry and/or Ca2+ release from internal Ca2+ stores. The control of Ca2+-store mobilization is ensured by a family of messengers comprising inositol 1,4,5 trisphosphate, cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate (NAADP). From recent works, new concepts have emerged where activation of the cells by outside stimuli, acting at the plasma membrane, results in the synthesis of multiple Ca2+-releasing messengers which may interact and shape complex Ca2+ signals in the cytosol as well as in the nucleus. This contribution will cover the most recent advances on NAADP signalling with some emphasis on neurons.
Synchrotron radiation X-ray scattering experiments were performed on unmyelinated pike olfactory ... more Synchrotron radiation X-ray scattering experiments were performed on unmyelinated pike olfactory nerves. The difference between the meridional and the equatorial traces of the 2-D spectra yielded the 1-D equatorial intensity of the macromolecular components oriented with respect to the nerve: axonal membranes, microtubules and other cytoskeletal filaments. These 1-D spectra display a diffuse band typical of bilayer membranes and, at small s, a few sharper bands reminiscent of microtubules. All the spectra merge at large s. The intensity of the axonal membrane was determined via a noise analysis of the nerve-dependent spectra, involving also the notion that the thickness of the membrane is finite. The shape of the intensity function indicated that the electron density profile is not centrosymmetric. The knowledge of intensity and thickness paved the way to the electron density profile via an ab initio solution of the phase problem. An iterative procedure was adopted: (i) choose the lattice D of a 1-D pseudo crystal, interpolate the intensity at the points sh = h/D, adopt an arbitrary set of initial phases and compute the profile; (ii) determine the phases corresponding to this profile truncated by the thickness D/2; (iii) repeat the operation with the updated phases until a stable result is obtained. This iterative procedure was carried out for different D-values, starting in each case from randomly generated phases: stable results were obtained in less than 10,000 iterations. Most importantly, for D in the vicinity of 200 A, the overwhelming majority of the profiles were congruent with each other. These profiles were strongly asymmetric and otherwise typical of biological membranes.
The effects of several agents, sugars, isotonic KCl, and a variety of drugs, on the structure of ... more The effects of several agents, sugars, isotonic KCl, and a variety of drugs, on the structure of the axonal membranes of unmyelinated pike olfactory nerve have been studied by synchrotron radiation X-ray scattering experiments. The main effects of the sugars are: (i) to increase the electron density of the extra-axonal space and thereby yield the absolute scale of the electron density profile; (ii) to osmotically stress the membrane and thus yield its elastic modulus of area compressibility, since the related strain, thickness dilation, is directly determined by the X-ray scattering experiments. Exposure to isotonic KCl, a depolarizing agent, induces membrane thickness to increase. The energy liberated in this process is a function of the amplitude of the dilation and of the elastic modulus of the membrane. This energy turns out to be close to the thermal energy liberated by the pike olfactory nerve during the initial phase of action potential that has previously been measured by others. Electrical depolarization thus seems to be accompanied by a thickness dilation of the axonal membrane. Another effect of isotonic KCl is to induce a large fraction of the membranes to pair by tight apposition of their extra-axonal faces. Local anaesthetics and some drugs have the effect of altering membrane thickness. All these observations are interpreted in terms of a modulation of the conformational disorder of the hydrocarbon chains of the lipid molecules.
An unusual inward current which is slowly elicited in the Xenopus oocyte membrane during sustaine... more An unusual inward current which is slowly elicited in the Xenopus oocyte membrane during sustained depolarization is reportedly carried by Na+. It is thought that Na+ selective channels are in some way induced to become voltage-sensitive by the depolarization. Earlier studies report that the induction process involves a phospholipase C and a protein kinase C as well as calcium ions. The present work investigated the origins of this calcium in the oocyte. We show that injection of the powerful Ca2+ chelator (BAPTA) in the oocyte, before induction of the Na+ channels, prevented the appearance of the Na+ current, confirming an important role for [Ca2+]i. However, in oocytes perfused with Ca2+ -free medium, induction of the channels could still be obtained, indicating that induction did not depend upon the entry of external Ca2+. Downmodulation of Ca2+ release from inositol 1,4,5-trisphosphate (InsP3)-sensitive stores with caffeine and with a low molecular weight heparin resulted in decreased or no Na+ currents. The results are discussed in terms of the contributions from other endogenous calcium-dependent conductances which can influence the Na+ current amplitudes and time courses. The results presented support the idea that intracellular Ca2+ increase principally due to Ca2+ released from InsP3-sensitive stores is needed by the enzyme systems to produce the depolarization-induced activation of the Na+ conductance in the Xenopus oocyte.
2010 Fifth IEEE International Symposium on Electronic Design, Test & Applications, 2010
Abstract A flexible hardware accelerator for full-search vector quantization (VQ) has been develo... more Abstract A flexible hardware accelerator for full-search vector quantization (VQ) has been developed as a component for a system on a programmable chip (SoPC) to use in real-time image compression and recognition applications. In the system, the number of elements ...
ABSTRACT Objectif DIABEO est un système de télémédecine utilisant un logiciel de carnet électroni... more ABSTRACT Objectif DIABEO est un système de télémédecine utilisant un logiciel de carnet électronique, téléchargé sur un PDA-phone, et couplé à une aide à la décision des doses d’insuline et à la possibilité de téléconsultations avec l’ensemble des données accessibles aux soignants via Internet. L’objectif de cette étude était d’évaluer l’efficacité de ce système à améliorer l’équilibre glycémique de patients diabétiques de type 1 (DT1) chroniquement mal équilibrés. Patients et Méthodes 180 adultes DT1 (> 1 an), traités par basal-bolus (> 6 mois, par pompe ou multi-injections) et avec une HbA1c > 8 % à au moins 2 reprises consécutives, ont été randomisés en 3 groupes, pendant 6 mois : contrôle avec suivi habituel par consultations trimestrielles (G1), DIABEO avec consultations trimestrielles (G2) et DIABEO couplé à des consultations téléphoniques tous les 15 j et sans consultation face-face (G3). Résultats A 6 mois, l’HbA1c est significativement plus basse dans les G2 (8,6 %, p = 0,022) et G3 (8,4%, p < 0,002) en comparaison du G1 (9,1 %). L’évolution de l’HbA1c entre 0 et 6 mois est également significativement meilleure (p < 0,001) pour les G2 (-0,5 %) et G3 (-0,7 %), en comparaison du G1 (+0,2 %, NS). Le pourcentage de patients atteignant un taux d’HbA1c < 7,5 % est plus élevé dans le G3 (19 %) que dans le G2 (8 %, NS) et G1 (3 %, p = 0,007). Le nombre d’hypoglycémies bénignes ou sévères n’est pas différent entre les 3 groupes. Le temps moyen cumulé de consultation sur 6 mois est de 1,2 h dans chaque groupe tandis que le temps total de prise en charge (incluant déplacement et attente des patients) est moindre dans le G3 (1,2 h, p < 0,001) que dans les G1 (7,1 h) et G2 (8,3 h). 66 % des patients du G2 et 75 % de ceux du G3 souhaitaient poursuivre l’utilisation de DIABEO. Conclusion Le système DIABEO permet d’améliorer significativement, à 6 mois, l’HbA1c de patients DT1 mal équilibrés, sans augmentation du risque hypoglycémique. De plus, associé aux consultations téléphoniques, il permet à un nombre plus élevé de patients d’atteindre un très bon contrôle glycémique, avec une meilleure efficience médicale et un gain de temps pour les patients. Une large majorité des patients souhaitent poursuivre l’utilisation au long cours de ce système, désormais en libre accès, pour patients et diabéto, via « Diabeo.com ».
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