313 resultados para Channel patterns
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Cognitive errors (CE) and coping strategies (CS) are the focus of most cognitive-behavioral treatments for incarcerated child molesters. Several studies have reported differences in CEs and CSs between child molesters and controls. However, the vast majority of these studies assessed cognitive errors and coping using questionnaires, which are known to present a number of important limitations. This pilot study aimed to compare the CEs and CSs of N = 17 incarcerated child abusers and N = 12 controls using observer-rated methods, namely the Cognitive Error Rating Scale (CERS; Drapeau et al., 2005) and the Coping Action Pattern Rating Scale (CAPRS; Perry, Drapeau, & Dunkley, 2005). Results showed that child molesters presented more cognitive errors, in particular positive selective abstraction, and lower coping functioning, such as escape strategies. Treatment and research implications, including the use of observer-rated methods, are discussed.
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Kidneys are the main regulator of salt homeostasis and blood pressure. In the distal region of the tubule active Na-transport is finely tuned. This transport is regulated by various hormonal pathways including aldosterone that regulates the reabsorption at the level of the ASDN, comprising the late DCT, the CNT and the CCD. In the ASDN, the amiloride-sensitive epithelial Na-channel (ENaC) plays a major role in Na-homeostasis, as evidenced by gain-of function mutations in the genes encoding ENaC, causing Liddle's syndrome, a severe form of salt-sensitive hypertension. In this disease, regulation of ENaC is compromised due to mutations that delete or mutate a PY-motif in ENaC. Such mutations interfere with Nedd4-2- dependent ubiquitylation of ENaC, leading to reduced endocytosis of the channel, and consequently to increased channel activity at the cell surface. After endocytosis ENaC is targeted to the lysosome and rapidly degraded. Similarly to other ubiquitylated and endocytosed plasma membrane proteins (such as the EGFR), it is likely that the multi-protein complex system ESCRT is involved. To investigate the involvement of this system we tested the role of one of the ESCRT proteins, Tsg101. Here we show that Tsg101 interacts endogenously and in transfected HEK-293 cells with all three ENaC sub-units. Furthermore, mutations of cytoplasmic lysines of ENaC subunits lead to the disruption of this interaction, indicating a potential involvement of ubiquitin in Tsg101 / ENaC interaction. Tsg101 knockdown in renal epithelial cells increases the total and cell surface pool of ENaC, thus implying TsglOl and consequently the ESCRT system in ENaC degradation by the endosomal/lysosomal system. - Les reins sont les principaux organes responsables de la régulation de la pression artérielle ainsi que de la balance saline du corps. Dans la région distale du tubule, le transport actif de sodium est finement régulé. Ce transport est contrôlé par plusieurs hormones comme l'aldostérone, qui régule la réabsorption au niveau de l'ASDN, segment comprenant la fin du DCT, le CNT et le CCD. Dans l'ASDN, le canal à sodium épithélial sensible à l'amiloride (ENaC) joue un rôle majeur dans l'homéostasie sodique, comme cela fut démontré par les mutations « gain de fonction » dans les gênes encodant ENaC, causant ainsi le syndrome de Liddle, une forme sévère d'hypertension sensible au sel. Dans cette maladie, la régulation d'ENaC est compromise du fait des mutations qui supprime ou mute le domaine PY présent sur les sous-unités d'ENaC. Ces mutations préviennent l'ubiquitylation d'ENaC par Nedd4-2, conduisant ainsi à une baisse de l'endocytose du canal et par conséquent une activité accrue d'ENaC à la surface membranaire. Après endocytose, ENaC est envoyé vers le lysosome et rapidement dégradé. Comme d'autres protéines membranaires ubiquitylées et endocytées (comme l'EGFR), il est probable que le complexe multi-protéique ESCRT est impliqué dans le transport d'ENaC au lysosome. Pour étudier l'implication du système d'ESCRT dans la régulation d'ENaC nous avons testé le rôle d'une protéine de ces complexes, TsglOl. Notre étude nous a permis de démontrer que TsglOl se lie aux trois sous-unités ENaC aussi bien en co-transfection dans des cellules HEK-293 que de manière endogène. De plus, nous avons pu démontrer l'importance de l'ubiquitine dans cette interaction par la mutation de toutes les lysines placées du côté cytoplasmique des sous-unités d'ENaC, empêchant ainsi l'ubiquitylation de ces sous-unités. Enfin, le « knockdown » de TsglOl dans des cellules épithéliales de rein induit une augmentation de l'expression d'ENaC aussi bien dans le «pool» total qu'à la surface membranaire, indiquant ainsi un rôle pour TsglOl et par conséquent du système d'ESCRT dans la dégradation d'ENaC par la voie endosome / lysosome. - Le corps humain est composé d'organes chacun spécialisé dans une fonction précise. Chaque organe est composé de cellules, qui assurent la fonction de l'organe en question. Ces cellules se caractérisent par : - une membrane qui leur permet d'isoler leur compartiment interne (milieu intracellulaire ou cytoplasme) du liquide externe (milieu extracellulaire), - un noyau, où l'ADN est situé, - des protéines, sortent d'unités fonctionnelles ayant une fonction bien définie dans la cellule. La séparation entre l'extérieure et l'intérieure de la cellule est essentielle pour le maintien des composants de ces milieux ainsi que pour la bonne fonction de l'organisme et des cellules. Parmi ces composants, le sodium joue un rôle essentiel car il conditionne le maintien de volume sanguin en participant au maintien du volume extracellulaire. Une augmentation du sodium dans l'organisme provoque donc une augmentation du volume sanguin et ainsi provoque une hypertension. De ce fait, le contrôle de la quantité de sodium présente dans l'organisme est essentiel pour le bon fonctionnement de l'organisme. Le sodium est apporté par l'alimentation, et c'est au niveau du rein que va s'effectuer le contrôle de la quantité de sodium qui va être retenue dans l'organisme pour le maintien d'une concentration normale de sodium dans le milieu extracellulaire. Le rein va se charger de réabsorber toutes sortes de solutés nécessaires pour l'organisme avant d'évacuer les déchets ou le surplus de ces solutés en produisant l'urine. Le rein va se charger de réabsorber le sodium grâce à différentes protéines, parmi elle, nous nous sommes intéressés à une protéine appelée ENaC. Cette protéine joue un rôle important dans la réabsorption du sodium, et lorsqu'elle fonctionne mal, comme il a pu être observé dans certaines maladies génétiques, il en résulte des problèmes d'hypo- ou d'hypertension. Les problèmes résultant du mauvais fonctionnement de cette protéine obligent donc la cellule à réguler efficacement ENaC par différents mécanismes, notamment en diminuant son expression et en dégradant le « surplus ». Dans cette travail de thèse, nous nous sommes intéressés au mécanisme impliqué dans la dégradation d'ENaC et plus précisément à un ensemble de protéines, appelé ESCRT, qui va se charger « d'escorter » une protéine vers un sous compartiment à l'intérieur de la cellule ou elle sera dégradée.
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PURPOSE: Little is known regarding cannabis administration routes for nonmedical use-that is, its delivery methods (e.g., joints, water pipe, food). Therefore, we examined the prevalence rates of different cannabis delivery methods and assessed the relationship of the distinct administration routes with problematic drug use. Subgroups of cannabis users were also investigated (i.e., "pure" cannabis users, previously described as employing a harmless route of administration, and water pipe users, previously described as using a harmful route of administration). METHODS: As part of the Cohort Study on Substance Use Risk Factors, 1,763 cannabis users answered questions concerning their drug use (i.e., routes of administration, problematic cannabis use, other illicit drug use). Descriptive statistics, latent class analysis, correlations and t-tests were assessed. RESULTS: The main administration route was "joints with tobacco"; other routes of administration had prevalence rates from 23.99% to 38.23%. In addition, increasing the number of administration routes was associated with more problematic cannabis use, as well as heavier illicit drug use. Water pipes without tobacco were especially linked to heavy drug use patterns, whereas "pure" cannabis use seemed less harmful. CONCLUSIONS: Our findings highlighted that diversification in routes of administration can be associated with heavier illicit drug use. This was especially true for water pipe users, whereas "pure" cannabis users, who did not mix cannabis with tobacco, were an exception. Indeed, these results may be useful for future preventive programs, which may need to focus on those who have diversified routes of administration for cannabis.
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Voltage-gated Na(+) channels (NaV channels) are specifically blocked by guanidinium toxins such as tetrodotoxin (TTX) and saxitoxin (STX) with nanomolar to micromolar affinity depending on key amino acid substitutions in the outer vestibule of the channel that vary with NaV gene isoforms. All NaV channels that have been studied exhibit a use-dependent enhancement of TTX/STX affinity when the channel is stimulated with brief repetitive voltage depolarizations from a hyperpolarized starting voltage. Two models have been proposed to explain the mechanism of TTX/STX use dependence: a conformational mechanism and a trapped ion mechanism. In this study, we used selectivity filter mutations (K1237R, K1237A, and K1237H) of the rat muscle NaV1.4 channel that are known to alter ionic selectivity and Ca(2+) permeability to test the trapped ion mechanism, which attributes use-dependent enhancement of toxin affinity to electrostatic repulsion between the bound toxin and Ca(2+) or Na(+) ions trapped inside the channel vestibule in the closed state. Our results indicate that TTX/STX use dependence is not relieved by mutations that enhance Ca(2+) permeability, suggesting that ion-toxin repulsion is not the primary factor that determines use dependence. Evidence now favors the idea that TTX/STX use dependence arises from conformational coupling of the voltage sensor domain or domains with residues in the toxin-binding site that are also involved in slow inactivation.
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The epithelial sodium channel (ENaC) is a key element for the maintenance of sodium balance and the regulation of blood pressure. Three homologous ENaC subunits (alpha, beta and gamma) assemble to form a highly Na+-selective channel. However, the subunit stoichiometry of ENaC has not yet been solved. Quantitative analysis of cell surface expression of ENaC alpha, beta and gamma subunits shows that they assemble according to a fixed stoichiometry, with alpha ENaC as the most abundant subunit. Functional assays based on differential sensitivities to channel blockers elicited by mutations tagging each alpha, beta and gamma subunit are consistent with a four subunit stoichiometry composed of two alpha, one beta and one gamma. Expression of concatameric cDNA constructs made of different combinations of ENaC subunits confirmed the four subunit channel stoichiometry and showed that the arrangement of the subunits around the channel pore consists of two alpha subunits separated by beta and gamma subunits.
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The fatty acid oxygenation up-regulated 2 (fou2) mutant in Arabidopsis thaliana creates a gain-of-function allele in a non-selective cation channel encoded by the Two Pore Channel 1 (TPC1) gene. This mutant genetically implicates cation fluxes in the control of the positive feedback loop whereby jasmonic acid (JA) stimulates its own synthesis. In this study we observed extensive transcriptome reprogramming in healthy fou2 leaves closely resembling that induced by treatment with methyl jasmonate, biotic stresses and the potassium starvation response. Proteomic analysis of fou2 leaves identified increased levels of seven biotic stress- and JA-inducible proteins. In agreement with these analyses, epistasis studies performed by crossing fou2 with aos indicated that elevated levels of JA in fou2 are the major determinant of the mutant phenotype. In addition, generation of fou2 aba1-5, fou2 etr1-1 and fou2 npr1-1 double mutants showed that the fou2 phenotype was only weakly affected by ABA levels and unaffected by mutations in NPR1 and ETR1. The results now suggest possible mechanisms whereby fou2 could induce JA synthesis/signaling early in the wound response. In contrast to fou2, transcriptome analysis of a loss-of-function allele of TPC1, tpc1-2, revealed no differential expression of JA biosynthesis genes in resting leaves. However, the analysis disclosed reduced mRNA levels of the pathogenesis-related genes PDF1.2a and THI2.1 in healthy and diseased tpc1-2 leaves. The results suggest that wild-type TPC1 contributes to their expression by mechanisms somewhat different from those affecting their expression in fou2.
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Temporal dynamical analysis in fire sequences recorded from 1969 to 2008 in Canton Ticino (Switzerland) was carried out by using the Allan Factor statistics. The obtained results show the presence of daily periodicities, superimposed to two time-scaling regimes. The daily cycle vanishes for sequences of higher altitude fires, for which a single scaling behaviour is observed.
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Total energy expenditure (TEE) and patterns of activity were measured by means of a heart rate (HR)-monitoring method in a group of 8-10-year-old children including 13 obese children (weight, 46 +/- 10 kg; fat mass: 32 +/- 9%) and 16 nonobese children (weight, 31 +/- 5 kg; fat mass, 18 +/- 5%). Time for sleeping was not statistically different in the two groups of children (596 +/- 33 vs. 582 +/- 43 min; p = NS). Obese children spent more time doing sedentary activities (400 +/- 129 vs. 295 +/- 127 min; p < 0.05) and less time in nonsedentary activities (449 +/- 126 vs. 563 +/- 135 min; p < 0.05) than nonobese children. Time spent in moderate or vigorous activity-i.e., time spent at a HR between 50% of the maximal O2 uptake (peak VO2) and 70% peak VO2 (moderate) and at a HR > or = 70% peak VO2 (vigorous)-was not statistically different in obese and nonobese children (88 +/- 69 vs. 52 +/- 35 min and 20 +/- 21 vs. 16 +/- 13 min, respectively; p = NS). TEE was significantly higher in the obese group than in the nonobese group (9.46 +/- 1.40 vs. 7.51 +/- 1.67 MJ/day; p < 0.01). The energy expenditure for physical activity (plus thermogenesis) was significantly higher in the obese children (3.98 +/- 1.30 vs. 2.94 +/- 1.39 MJ/day; p < 0.05). The proportion of TEE daily devoted to physical activity (plus thermogenesis) was not significantly different in the two groups, as shown by the ratio between TEE and the postabsorptive metabolic rate (PMR): 1.72 +/- 0.25 obese vs 1.61 +/- 0.28 non-obese. In conclusion, in free-living conditions obese children have a higher TEE than do nonobese children, despite the greater time devoted to sedentary activities. The higher energy cost to perform weight-bearing activities as well as the higher absolute PMR of obese children help explain this apparent paradox.
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BACKGROUND: Mutations in the SCN9A gene cause chronic pain and pain insensitivity syndromes. We aimed to study clinical, genetic, and electrophysiological features of paroxysmal extreme pain disorder (PEPD) caused by a novel SCN9A mutation. METHODS: Description of a 4-generation family suffering from PEPD with clinical, genetic and electrophysiological studies including patch clamp experiments assessing response to drug and temperature. RESULTS: The family was clinically comparable to those reported previously with the exception of a favorable effect of cold exposure and a lack of drug efficacy including with carbamazepine, a proposed treatment for PEPD. A novel p.L1612P mutation in the Nav1.7 voltage-gated sodium channel was found in the four affected family members tested. Electrophysiologically the mutation substantially depolarized the steady-state inactivation curve (V1/2 from -61.8 ± 4.5 mV to -30.9 ± 2.2 mV, n = 4 and 7, P < 0.001), significantly increased ramp current (from 1.8% to 3.4%, n = 10 and 12) and shortened recovery from inactivation (from 7.2 ± 5.6 ms to 2.2 ± 1.5 ms, n = 11 and 10). However, there was no persistent current. Cold exposure reduced peak current and prolonged recovery from inactivation in wild-type and mutated channels. Amitriptyline only slightly corrected the steady-state inactivation shift of the mutated channel, which is consistent with the lack of clinical benefit. CONCLUSIONS: The novel p.L1612P Nav1.7 mutation expands the PEPD spectrum with a unique combination of clinical symptoms and electrophysiological properties. Symptoms are partially responsive to temperature but not to drug therapy. In vitro trials of sodium channel blockers or temperature dependence might help predict treatment efficacy in PEPD.
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The Spanish sand racer (Psammodromus hispanicus) has been recently split into three distinct species: P. hispanicus, P. edwardsianus, and P. occidentalis. Some morphological differences have been reported but there is as yet no description allowing unambiguous identification of the three species. Here, we describe differentiation in body measurements, scalation traits, and colour traits as well as in the degree of sexual dimorphism. Our results show that P. edwardsianus can be easily distinguished by the presence of a supralabial scale below the subocular scale, which is absent in the other two species. Psammodromus hispanicus and P. occidentalis can be distinguished by the number of femoral pores, throat scales and ocelli, and the relative width of the anal scale. The degree of sexual size dimorphism and sexual colour dimorphism substantially differs among species, suggesting that different scenarios of sexual and natural selection may exist for each species. Moreover, sexually selected traits (nuptial colouration, ocelli, and femoral pores) significantly differ among species, suggesting that visual and chemical communication may also differ among species. Such differences could prevent reproduction and gene flow at secondary contact zones, potentially reinforcing isolation and speciation within this group of lizards.
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Whereas previous studies have shown that opening of the mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channel protects the adult heart against ischemia-reperfusion injury, it remains to be established whether this mechanism also operates in the developing heart. Isolated spontaneously beating hearts from 4-day-old chick embryos were subjected to 30 min of anoxia followed by 60 min of reoxygenation. The chrono-, dromo-, and inotropic disturbances, as well as alterations of the electromechanical delay (EMD), reflecting excitation-contraction (E-C) coupling, were investigated. Production of reactive oxygen species (ROS) in the ventricle was determined using the intracellular fluorescent probe 2',7'-dichlorofluorescin (DCFH). Effects of the specific mitoK(ATP) channel opener diazoxide (Diazo, 50 microM) or the blocker 5-hydroxydecanoate (5-HD, 500 microM), the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 50 microM), the antioxidant N-(2-mercaptopropionyl)glycine (MPG, 1 mM), and the PKC inhibitor chelerythrine (Chel, 5 microM) on oxidative stress and postanoxic functional recovery were determined. Under normoxia, the baseline parameters were not altered by any of these pharmacological agents, alone or in combination. During the first 20 min of postanoxic reoxygenation, Diazo doubled the peak of ROS production and, interestingly, accelerated recovery of ventricular EMD and the PR interval. Diazo-induced ROS production was suppressed by 5-HD, MPG, or L-NAME, but not by Chel. Protection of ventricular EMD by Diazo was abolished by 5-HD, MPG, L-NAME, or Chel, whereas protection of the PR interval was abolished by L-NAME exclusively. Thus pharmacological opening of the mitoK(ATP) channel selectively improves postanoxic recovery of cell-to-cell communication and ventricular E-C coupling. Although the NO-, ROS-, and PKC-dependent pathways also seem to be involved in this cardioprotection, their interrelation in the developing heart can differ markedly from that in the adult myocardium.
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RÉSUMÉ Introduction: l'histoire naturelle et la physiopathologie des infarctus de la moelle épinière restent largement inconnues. En effet, la plupart des études cliniques portent sur des patients qui ont souffert d'infarctus médullaire secondaire à des chirurgies aortiques ou des hypotensions prolongées. Méthode: ce travail analyse les données cliniques, le laboratoire, l'imagerie (IRM) et l'évolution de 27 patients souffrant d'infarctus de la moelle épinière admis dans le service de Neurologie du CHUV. Parmi ces patients, il y avait 11 hommes et 16 femmes (âge moyen de 56 ans, tranche d'âge de 19 à 80 ans). Résultats: dix patients (37%) souffraient d'infarctus de l'artère spinale antérieure, 4 (15%) d'infarctus unilatéraux antérieurs, 4 (15%) unilatéraux postérieurs, 3 (11%) d'infarctus centraux, 2 (7%) d'infarctus des artères spinales postérieures, 2 (7%) d'infarctus transverse tandis que 2 patients présentaient des tableaux cliniques inclassables. Vingt patients (74%) n'avaient pas d'étiologie identifiable. Les patients avec infarctus centraux ou transverses présentaient fréquemment (40%) des artériopathies périphériques et tous les infarctus transverses survenaient à la suite d'hypotensions artérielles prolongées. Le début de tous les autres types d'infarctus était associé à des facteurs mécaniques (p=0.02} et ces patients avaient fréquemment des pathologies du rachis (p=0.003) au niveau de la lésion médullaire. Dans ces cas, les données cliniques suggèrent une lésion d'une racine nerveuse au niveau de l'infarctus médullaire compromettant mécaniquement le flux de son artère radiculaire. L'évolution clinique était généralement favorable, seuls 13 patients (48%) présentaient une atteinte significative de la marche à la sortie de l'hôpital. Conclusion: ce travail montre qu'il existe 2 types principaux d'infarctus de la moelle épinière : d'une part les infarctus dans le territoire d'une artère radiculaire (infarctus de l'artère spinale antérieure, des artères spinales postérieures et infarctus unilatéraux) et d'autre part les hypoperfusions régionales globales de la moelle épinière (infarctus centraux et transverses). Chacune de ces 2 catégories d'infarctus ont des caractéristiques cliniques, radiologiques, physiopathologiques et pronostiques distinctes.
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Many studies have provided evidence that prey adjust their behaviour to adaptively balance the fitness effects of reproduction and predation risk. Nocturnal terrestrial animals should deal with a range of environmental conditions during the reproductive season at the breeding sites, including a variable amount of natural ambient light. High degrees of illumination are expected to minimize those behaviours that might increase the animal detection by predators. Therefore, under habitat variable brightness conditions and in different ecosystems, the above mentioned behaviours are expected to depend on the variation in predation risk. Although moon effects on amphibian biology have been recognized, the direction of this influence is rather controversial with evidences of both increased and depressed activity under full moon. We tested in four nocturnal amphibian species (Hyla intermedia, Rana dalmatina, Rana italica, Salamandrina perspicillata) the effects of different (i) light conditions and (ii) habitats (open land vs. dense forest) on the reproductive phenology. Our results showed that the effects of the lunar cycle on the study species are associated with the change in luminosity, and there is no evidence of an endogenous rhythm controlled by biological clocks. The habitat type conditioned the amphibian reproductive strategy in relation to moon phases. Open habitat breeders (e. g., ponds with no canopy cover) strongly avoided conditions with high brightness, whereas forest habitat breeders were apparently unaffected by the different moon phases. Indeed, for all the studied species no effects of the moon phase itself on the considered metrics were found. Rather, the considered amphibian species seem to be conditioned mainly by moonlight irrespective of the moon phase. The two anurans spawning in open habitat apparently adjust their oviposition timing by balancing the fitness effects of the risk to be detected by predators and the reproduction.
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Purpose: To identify patterns of initially pain freedom response in patients with classical trigeminal neuralgia (CTN) with Gamma Knife surgery (GKS) and to compare their associated hypoesthesia and recurrence rates. Methods: In this study we analysed only 497 patients treated between July 1992 and November 2010, with a follow-up longer than 1 year, after excluding megadolichobasilar artery and multiple sclerosis related trigeminal neuralgia, as well as the second GKS treatments so as to have only cases with CTN and single radiosurgical treatment. GKS using a Gamma Knife (model B or C or Perfexion) was performed, based on both MRI and computer tomography (CT) targeting. A single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.8 mm (range 4.5-14) anteriorly to the emergence of the nerve. A median maximum dose of 85 Gy (range 70-90) was delivered. After empiric methods but also by using a chart with clear cut-off periods of pain free distribution, we were able to divide the initially pain free patients into 3 separate groups: within the first 48 hours, after 48 hours till 30 days and after 30 days, respectively. Results: The median follow- up period was 43.75 months (range 12-174.41). Four hundred and fifty-four patients (91.75%) were initially pain free in a median time of 10 days (range 1-459): 169 (37.2%) became pain free within the first 48 hours (pf<=48 h), compared to 194 (42.8%) between the 3-rd day and the day 30 (pf (>48 h, <=30 d)), inclusively and 91 (20%) patients after 30 days (pf>30d). Differences in terms of postoperative hypoesthesia were found with a p value of 0.014 as follows: the group pf<=48 h had 18 (13.7%) compared to pf (>48 h, <=30 d) with 30 (19%) and pf>30d with 22 (30.5%) patients developing a postoperative GKS hypoesthesia. One hundred and fifty seven (34.4%) patients initially pain free experienced a recurrence with a median delay of 24 months (range 0.62-150.06). There were no statistically significant differences between the three groups concerning recurrence (p value of 0.515). Conclusions: An important number of patients (169 cases, 37.2%) became pain free in the first 48 hours. Hypoesthesia rate was higher within the group becoming pain free after 30 days with a statistically significant difference between the three populations (p= 0.014). Further analysis will eventually help to elucidate the differences observed among groups.