•Samples with different chemical composition showed the same behavior in relation to their magnetic response.•Samples with aging state I exhibits magnetic response at the carbide boundaries.•For ...advanced aging states no magnetic response is observed at microscopic scale.
HP steels are commonly used in steam reforming tubes, which are exposed to harsh operational conditions causing microstructural changes. These microstructural changes cause variations in the magnetic properties, which can be measured by different techniques. This work aims at the measurement of the magnetic and electric variations in HP-Nb modified alloys with different chemical composition using scanning probe microscopy (SPM) techniques. The results show that, despite the microstructural change due to variation of chemical composition, samples with aging state I exhibit a magnetic response at the carbides boundary, while for advanced aging states, the magnetic response is not evidenced.
BACKGROUNDThere is a controversy in the literature whether deep compared with moderate neuromuscular block (NMB) improves surgical conditions for laparoscopic surgery.
OBJECTIVESThe primary outcome ...measure was to examine whether switching from moderate to deep NMB improves surgical conditions for laparoscopic surgery in the obese; secondary outcome measures were changes in intra-abdominal pressure, time required to perform the gastrojejunal anastomosis and peri-operative surgical complications.
DESIGNA single-centre, randomised controlled study. Each patient was taken as their own control and examined twiceat the first evaluation (E1), all patients had a moderate NMB, thereafter patients were randomised to deep or moderate block and a second evaluation (E2) was performed within 10 min. Patients with excellent rating at E1 were excluded from E2, as their surgical condition could not be further improved.
SETTINGUniversity Hospital France.
PATIENTSPatients undergoing laparoscopic gastric bypass surgery under general anaesthesia were included. Main exclusion criteria were hypersensitivity to the drugs used and absence of written informed consent.
INTERVENTIONSAccording to the group assignment, patients received bolus doses of rocuronium or 0.9% saline.
MAIN OUTCOME MEASURESSurgical conditions were assessed with a 4-point rating scale. Intra-operative adverse events were assessed with the Kaafarani-classification and postoperative complications with the Clavien-Dindo classification.
RESULTSEighty-nine patients were initially included and data from 85 could be assessed at E1; surgical rating was excellent in 20, good in 35, acceptable in 18, poor in 12. After excluding those with an excellent rating, the remaining 65 patients were randomly assigned to deep or moderate block. At E2, an improvement of surgical conditions was observed in 29 out of 34 patients with deep block and in four out of 31 with moderate block; P < 0.0001. Poor surgical conditions were more frequently associated with surgical complications (61.5 versus 15.3%; P < 0.001).
CONCLUSIONSwitching from moderate to deep block improves surgical conditions. Poor surgical conditions were associated with a higher incidence of surgical complications.
TRIAL REGISTRATIONClinicalTrials.gov identifierNCT02118844
Purkinje cells (PC) control spike timing of neighboring PC by their recurrent axon collaterals. These synapses underlie fast cerebellar oscillations and are characterized by a strong facilitation ...within a time window of <20 ms during paired-pulse protocols. PC express high levels of the fast Ca2+ buffer protein calbindin D-28k (CB). As expected from the absence of a fast Ca2+ buffer, presynaptic action potential-evoked Ca2+i transients were previously shown to be bigger in PC boutons of young (second postnatal week) CB-/- mice, yet IPSC mean amplitudes remained unaltered in connected CB-/- PC. Since PC spine morphology is altered in adult CB-/- mice (longer necks, larger spine head volume), we summoned that morphological compensation/adaptation mechanisms might also be induced in CB-/- PC axon collaterals including boutons. In these mice, biocytin-filled PC reconstructions revealed that the number of axonal varicosities per PC axon collateral was augmented, mostly confined to the granule cell layer. Additionally, the volume of individual boutons was increased, evidenced from z-stacks of confocal images. EM analysis of PC-PC synapses revealed an enhancement in active zone (AZ) length by approximately 23%, paralleled by a higher number of docked vesicles per AZ in CB-/- boutons. Moreover, synaptic cleft width was larger in CB-/- (23.8 ± 0.43 nm) compared to wild type (21.17 ± 0.39 nm) synapses. We propose that the morphological changes, i.e. the larger bouton volume, the enhanced AZ length and the higher number of docked vesicles, in combination with the increase in synaptic cleft width likely modifies the GABA release properties at this synapse in CB-/- mice. We view these changes as adaptation/homeostatic mechanisms to likely maintain (preserve) characteristics of synaptic transmission in the absence of the fast Ca2+ buffer CB. Our study provides further evidence on the functioning of the Ca2+ homeostasome.
We investigated the effect of a synthetic cannabinoid, WIN 55,212-2 on excitatory postsynaptic currents (EPSCs) evoked by stimulation of Schaffer collaterals in CA1 pyramidal cells. Bath application ...of WIN 55,212-2 reduced the amplitude of EPSCs in dose-dependent manner tested between 0.01nM and 30μM. In rats and mice, this cannabinoid ligand inhibited excitatory synapses in two steps at the nM and μM concentrations. When the function of CB1 cannabinoid receptors (CB1R) was impaired, either by the application of a CB1R antagonist AM251, or by using CB1R knockout mice, WIN 55,212-2 in μM concentrations could still significantly reduced the amplitude of EPSCs. WIN 55,212-2 likely affected the efficacy of excitatory transmission only at presynaptic sites, since both at low and high doses the paired pulse ratio of EPSC amplitude was significantly increased. The inactive enantiomer, WIN 55,212-3, mimicked the effect of WIN 55,212-2 applied in high doses. In further experiments we found that the CB1R-independent effect of 10μM WIN 55,212-2 at glutamatergic synapses was fully abolished, when slices were pre-treated with ω-conotoxin GVIA, but not with ω-agatoxin IVA.
These data suggest that, in the hippocampus, WIN 55,212-2 reduces glutamate release from Schaffer collaterals solely via CB1Rs in the nM concentration range, whereas in μM concentrations, WIN 55,212-2 suppresses excitatory transmission, in addition to activation of CB1Rs, by directly blocking N-type voltage-gated Ca2+ channels independent of CB1Rs.
Visa riposte au projet de souveraineté européenne Le spécialiste américain des cartes bancaires veut distribuer 4 millions de cartes en partenariat avec le groupe BPCE d'ici aux JO 2024, sur ...lesquelles ne figurera pas le sigle Carte Bleue. Avec le secteur financier européen veut inventer une alternative aux géants américains Visa et Mastercard dans le domaine du paiement. Mais les acteurs américains n'entendent pas se laisser faire. Visa s'apprête à annoncer lundi prochain sa première contre-mesure, en adressant un message aux acteurs français, très actifs dans ce projet. compte, d'ici aux JO de 2024, inonder le marché français avec 4 millions de cartes bancaires qui risquent de dénoter : le fameux logo « CB » (Carte Bleue) qui figure sur les cartes bancaires en France et dans des dizaines de milliers de commerces en sera absent. Et pour cause : avec cette carte « JO », qui sera émise par BPCE, Visa compte se passer des services du Groupement des Cartes Bancaires (GIE CB), l'entité qui réunit la plupart des établissements français afin d'assurer l'interopérabilité entre établissements dans le domaine de la monétique. Incontournables Aux yeux du public, il s'agira de cartes classiques stylisées, qui arboreront les quatre anneaux olympiques, ainsi que le logo de l'opérateur américain et celui de la banque émettrice. « Visa est le partenaire exclusif des Jeux Olympiques depuis plus de trente ans », justifie Charlotte Hogg, la directrice générale de Visa Europe. « C'est une manière de montrer que Visa est indispensable dans le paiement en France », glisse un spécialiste du secteur. A travers la France, Visa s'adresse plus largement à l'Europe. Il faut dire que l'EPI ne cache pas son jeu : les auteurs du projet, soit une soutenues par Bruxelles, visent à créer un schéma de paiement commun à l'ensemble de l'Union afin de mettre fin à la fragmentation du marché sur le Vieux Continent pour se passer de l'intermédiation des géants américains Visa et Mastercard. Ces derniers sont en effet parvenus à se rendre utilisables, voire incontournables, partout en Europe. Pour mener à bien son opération, Visa compte sur son partenaire BPCE, qui n'est autre que le premier fournisseur de cartes à l'échelle européenne. La banque se défend cependant de vouloir trahir le projet paneuropéen. « Visa est un partenaire historique du Groupe BPCE, explique Jean-Yves Forel, le directeur général du programme Paris 2024. Cela ne remet pas en cause le partenariat du groupe avec le GIE des Cartes Bancaires. Ni notre engagement dans EPI. » Reste que ces futures cartes Visa exclusifs resteront en circulation pendant plusieurs années en France, étant donné la durée de vie moyenne relativement élevée de ce moyen de paiement, soit un peu plus de deux ans. Un temps pendant lequel le sigle d'EPI ne se répandra pas aussi facilement que le souhaiteraient les porteurs du projet. Or, pour qu'il soit viable, il nécessite une adoption à la fois massive et rapide. Mardi, le gouverneur de la Banque de France, François Villeroy de Galhau, rappelait que le projet EPI « est une course contre la montre » essentielle à la souveraineté de l'Europe dans le domaine du paiement. Gabriel Nedelec
► CB1Rs have high density in three layers of the frontal cortex of the rat and mouse. ► CB1Rs are present in frontocortical glutamatergic and serotonergic nerve terminals. ► CB1R activation decreases ...evoked glutamate release in rat and mouse synaptosomes. ► CB1R activation decreases serotonin release in rat frontocortical synaptosomes. ► Evoked glutamate and serotonin release is greater in the CB1R KO versus WT mice.
Both the serotonergic and endocannabinoid systems modulate frontocortical glutamate release; thus they are well positioned to participate in the pathogenesis of psychiatric disorders. With the help of fluorescent and confocal microscopy, we localized the CB1 cannabinoid receptor (CB1R) in VGLUT1- and 2- (i.e. glutamatergic) and serotonin transporter- (i.e. serotonergic) -positive fibers and nerve terminals in the mouse and rat frontal cortex.
CB1R activation by the synthetic agonists, WIN55212-2 (1μM) and R-methanandamide (1μM) inhibited the simultaneously measured evoked Ca2+-dependent release of 14Cglutamate and 3Hserotonin from frontocortical nerve terminals of Wistar rats, in a fashion sensitive to the CB1R antagonists, O-2050 (1μM) and LY320135 (5μM). CB1R agonists also inhibited the evoked release of 14Cglutamate in C57BL/6J mice in a reversible fashion upon washout.
Interestingly, the evoked release of 14Cglutamate and 3Hserotonin was significantly greater in the CB1R knockout CD-1 mice. Furthermore, CB1R binding experiments revealed similar frontocortical CB1R density in the rat and the CD-1 mouse. Still, the evoked release of 3Hserotonin was modulated by neither CB1R agonists nor antagonists in wild-type CD-1 or C57BL/6J mice.
Altogether, this is the first study to demonstrate functional presynaptic CB1Rs in frontocortical glutamatergic and serotonergic terminals, revealing species differences.
The endocannabinoid 2-arachidonoylglycerol (2-AG) regulates neurotransmission and neuroinflammation by activating CB1 cannabinoid receptors on neurons and CB2 cannabinoid receptors on microglia. ...Enzymes that hydrolyze 2-AG, such as monoacylglycerol lipase, regulate the accumulation and efficacy of 2-AG at cannabinoid receptors. We found that the recently described serine hydrolase alpha-beta-hydrolase domain 6 (ABHD6) also controls the accumulation and efficacy of 2-AG at cannabinoid receptors. In cells from the BV-2 microglia cell line, ABHD6 knockdown reduced hydrolysis of 2-AG and increased the efficacy with which 2-AG can stimulate CB2-mediated cell migration. ABHD6 was expressed by neurons in primary culture and its inhibition led to activity-dependent accumulation of 2-AG. In adult mouse cortex, ABHD6 was located postsynaptically and its selective inhibition allowed the induction of CB1-dependent long-term depression by otherwise subthreshold stimulation. Our results indicate that ABHD6 is a rate-limiting step of 2-AG signaling and is therefore a bona fide member of the endocannabinoid signaling system.
Spliceosomal small nuclear RNAs (snRNAs) are modified by small Cajal body (CB)-specific ribonucleoproteins (scaRNPs) to ensure snRNP biogenesis and pre-mRNA splicing. However, the function and ...subcellular site of snRNA modification are largely unknown. We show that CB localization of the protein Nopp140 is essential for concentration of scaRNPs in that nuclear condensate; and that phosphorylation by casein kinase 2 (CK2) at ∼80 serines targets Nopp140 to CBs. Transiting through CBs, snRNAs are apparently modified by scaRNPs. Indeed, Nopp140 knockdown-mediated release of scaRNPs from CBs severely compromises 2'-O-methylation of spliceosomal snRNAs, identifying CBs as the site of scaRNP catalysis. Additionally, alternative splicing patterns change indicating that these modifications in U1, U2, U5, and U12 snRNAs safeguard splicing fidelity. Given the importance of CK2 in this pathway, compromised splicing could underlie the mode of action of small molecule CK2 inhibitors currently considered for therapy in cholangiocarcinoma, hematological malignancies, and COVID-19.
The CB2R agonist AM1710, examined in animal models of peripheral neuropathy, is effective in controlling aberrant light touch sensitivity, referred to as mechanical allodynia. However, nonspecific ...binding of AM1710 to CB1R, either peripherally or centrally, could be partially responsible for the analgesic effects of AM1710. Thus, we sought to determine in mice whether spinal (intrathecal; i.t.) or peripheral AM1710 administration could lead to anti‐allodynia by reducing the protein expression of spinal and dorsal root ganglia (DRG) proinflammatory cytokines and elevating the anti‐inflammatory cytokine interleukin‐10 (IL‐10) in the absence of CB1R. Macrophage cell cultures were examined to characterize AM1710‐mediated suppression of the proinflammatory cytokine tumor necrosis factor‐alpha (TNF‐α). Either i.p. or i.t. AM1710 reversed CCI‐induced mechanical allodynia to sham levels in CB1R (−/−), (+/−), (+/+) mice. CCI‐induced neuropathy decreased IL‐10 immunoreactivity (IR) in the dorsal root ganglia (DRG) and the dorsal horn of the spinal cord, with i.t. AM1710 restoring basal IL‐10 IR. CCI‐induced elevations in proinflammatory cytokine IR were decreased within the spinal cord only after i.t. AM1710 in all mouse genotypes. Meanwhile, within DRG tissue from neuropathic mice, proinflammatory cytokines were decreased following either i.p. or i.t. AM1710. Analysis of cultured supernatants revealed AM1710 decreased TNF‐alpha protein. We conclude that CB1R is dispensable for either peripheral or central anti‐allodynic actions of AM1710 in neuropathic mice. Cannabinoid CB2R agonists produce heightened spinal IL‐10 which may be clinically relevant to successfully treat neuropathic pain.
Either i.p. or i.t. AM1710 reversed CCI‐induced mechanical allodynia in CB1R (−/−), (+/−), (+/+) mice similar to sham control threshold levels. The absence of the CB1R following CCI‐induced neuropathy revealed greater significant increases in IL‐10 immunoreactivity (IR) in the dorsal root ganglia (DRG) and the dorsal horn of the spinal cord in (−/−) and (+/−) mice that was further elevated following i.t. and i.p. AM1710. The absence of CB1R may allow for enhanced tissue/axon damage‐associated signaling to the DRG and spinal cord, resulting in endogenous compensatory increases in IL‐10 expression.
Les établissements bancaires s'intéressent à la biométrie pour confirmer le règlement des achats A l'heure où Bruxelles leur demande d'être plus exigeantes pour faire baisser la fraude sur les ...paiements en ligne, les banques pourraient déployer des solutions biométriques auprès de leurs clients. La biométrie a de beaux jours devant elle dans le secteur des paiements. Les solutions d'identification des consommateurs basées sur leur empreinte digitale, leur voix, ou leur image, ont de fortes chances de se répandre A partir de la mi-septembre, et en vertu de la directive DSP2, les banques devront en effet être particulièrement rigoureuses pour vérifier que les transactions réalisées sur des sites d'e-commerce ne sont pas le fait de fraudeurs. Résultat : elles risquent de demander plus souvent qu'avant aux cyber-acheteurs de confirmer leur identité pour valider leur achat. Un risque d'abandon du panier d'achats Cette étape - baptisée « authentification forte » dans le jargon des spécialistes - n'est pas une nouveauté pour les acheteurs. Il n'empêche, les commerçants redoutent que les authentifications fortes se multiplient avec DSP2 et dissuadent des consommateurs de régler leur « panier d'achats ». D'où l'intérêt de solutions qui permettraient par exemple à un consommateur de confirmer son identité et valider son achat sur Internet simplement en posant son doigt sur son téléphone portable. « On travaille avec les banques à mettre en place des solutions d'identification par la biométrie qui vont beaucoup faciliter l'authentification », explique ainsi Olivier Gabrielli, responsable innovation et paiement digital chez Mastercard, beaucoup de banques commencent à avoir des solutions en la matière ». En France, les banques sont d'autant plus susceptibles de s'intéresser à ces solutions que la validation des achats pas SMS ne répond pas aux exigences européennes de sécurité des paiements qui s'appliqueront dans quelques mois. Plusieurs acteurs de la Place misent sur un délai de trois ans environ pour trouver des alternatives. Les solutions biométriques ont toutes les chances d'en faire partie. Elles ne seront cependant pas les seules. « Les banques ont l'obligation de servir tous leurs clients. Tous n'ont pas un smartphone qui permet d'utiliser la biométrie et tous ne veulent pas l'utiliser. », explique Loÿs Moulin, directeur chez Cartes Bancaires CB, l'organisation qui pilote le système de paiement par carte en France. S. P.
PDF
