55 research outputs found

    Elimination of the BKCa Channel's High-Affinity Ca2+ Sensitivity

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    We report here a combination of site-directed mutations that eliminate the high-affinity Ca2+ response of the large-conductance Ca2+-activated K+ channel (BKCa), leaving only a low-affinity response blocked by high concentrations of Mg2+. Mutations at two sites are required, the “Ca2+ bowl,” which has been implicated previously in Ca2+ binding, and M513, at the end of the channel's seventh hydrophobic segment. Energetic analyses of mutations at these positions, alone and in combination, argue that the BKCa channel contains three types of Ca2+ binding sites, one of low affinity that is Mg2+ sensitive (as has been suggested previously) and two of higher affinity that have similar binding characteristics and contribute approximately equally to the power of Ca2+ to influence channel opening. Estimates of the binding characteristics of the BKCa channel's high-affinity Ca2+-binding sites are provided

    Autistic Disorder in Patients with Williams-Beuren Syndrome: A Reconsideration of the Williams-Beuren Syndrome Phenotype

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    International audienceBackground: Williams-Beuren syndrome (WBS), a rare developmental disorder caused by deletion of contiguous genes at 7q11.23, has been characterized by strengths in socialization (overfriendliness) and communication (excessive talkativeness). WBS has been often considered as the polar opposite behavioral phenotype to autism. Our objective was to better understand the range of phenotypic expression in WBS and the relationship between WBS and autistic disorder. Methodology: The study was conducted on 9 French individuals aged from 4 to 37 years old with autistic disorder associated with WBS. Behavioral assessments were performed using Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) scales. Molecular characterization of the WBS critical region was performed by FISH. Findings: FISH analysis indicated that all 9 patients displayed the common WBS deletion. All 9 patients met ADI-R and ADOS diagnostic criteria for autism, displaying stereotypies and severe impairments in social interaction and communication (including the absence of expressive language). Additionally, patients showed improvement in social communication over time. Conclusions: The results indicate that comorbid autism and WBS is more frequent than expected and suggest that the common WBS deletion can result in a continuum of social communication impairment, ranging from excessive talkativeness and overfriendliness to absence of verbal language and poor social relationships. Appreciation of the possible co-occurrence of WBS and autism challenges the common view that WBS represents the opposite behavioral phenotype of autism, and might lead to improved recognition of WBS in individuals diagnosed with autism

    Familial Autoimmune Thyroid Disease as a Risk Factor for Regression in Children with Autism Spectrum Disorder: A CPEA Study

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    A multicenter study of 308 children with Autism Spectrum Disorder (ASD) was conducted through the Collaborative Programs of Excellence in Autism (CPEA), sponsored by the National Institute of Child Health and Human Development, to compare the family history of autoimmune disorders in children with ASD with and without a history of regression. A history of regression was determined from the results of the Autism Diagnostic Interview-Revised (ADI-R). Family history of autoimmune disorders was obtained by telephone interview. Regression was significantly associated with a family history of autoimmune disorders (adjusted OR=1.89; 95% CI: 1.17, 3.10). The only specific autoimmune disorder found to be associated with regression was autoimmune thyroid disease (adjusted OR=2.09; 95% CI: 1.28, 3.41).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43035/1/10803_2005_Article_71.pd

    Mobilité du phosphore sédimentaire en contexte de retenues de barrage hydroélectrique

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    Internal sedimentary phosphorus (P) load cause delay time in eutrophication recovery, especially in dam-reservoir systems where P stock are important. Then, the study of sedimentary P mobility in dam-reservoirs allow to better explain P geochemistry in this context and further to adapt management restauration policies. This study highlights the impact of three cascade dams (Age Complex, Creuse, France) on the distribution of sedimentary P along a fluvial continuum. In the impoundments studied, TP levels averaged 1.59 ± 0.51 mgP /g DW and increased towards dams. This contrast with the low and constant concentrations observed in the fluvial parts. In reservoirs, chemical fractionation showed that more than 50% of the extracted P was associated with the ascorbate fraction. The association of P to amorphous Fe oxi-hydroxides in the fine particles accumulated closed to the dam is the major factor explaining the longitudinal variations of the TP contents. In addition, the high levels of P associated with these redox-sensitive phases and the development of a hypoxic hypolimnion in studied reservoirs reveal the high potential for sediment P mobilization. Moreover, in aerobic conditions, a risk of mobilization resulting from an equilibrium concentration between solute and solid fraction exists. The determination of the EPC0 threshold value underlined the spatial evolution of the sink / source role of the sediment with respect to the P, between the reservoirs of the same complex. Finally, the study of sedimentary P mobility in the laboratory, following two successive aerobic and anaerobic cycles, showed that redox potential oscillation observed in the reservoirs, favors the mobilization of the sedimentary P. The geochemistry of iron and the quality of dissolved organic matter appear to be involved in the mobility of P.La charge interne en phosphore (P) sĂ©dimentaire stockĂ©e dans les retenues de barrages retarde la restauration du processus d’eutrophisation. Ainsi, l’étude de la mobilitĂ© du P sĂ©dimentaire dans les retenues de barrage permet d’une part de comprendre son cycle gĂ©ochimique dans ces systĂšmes, d’autre part de mieux apprĂ©hender les politiques de gestions de restauration des milieux. Cette Ă©tude met en Ă©vidence l’impact de trois barrages en cascade (Complexe de l’Age, Creuse, France) sur la distribution du P sĂ©dimentaire le long d’un continuum fluviatile. Dans les retenues Ă©tudiĂ©es, les teneurs en TP sont en moyenne de 1,59 ± 0,51 mgP/gsec et augmentent en direction des barrages. Ceci contraste avec les faibles teneurs observĂ©es dans les parties fluviatiles. Dans les rĂ©servoirs, le fractionnement chimique a montrĂ© que plus de 50% du P extrait Ă©tait associĂ© Ă  la fraction ascorbate. L’association du P avec les oxy-hydroxydes de Fe amorphes dans les particules fines des sĂ©diments accumulĂ©es prĂšs du barrage, s’avĂšre ĂȘtre le facteur majeur expliquant les variations longitudinales des teneurs en TP. De plus, ces fortes teneurs associĂ©es Ă  ces phases redox-sensibles et la mise en Ă©vidence d’un hypolimnion anoxique, rĂ©vĂšle le fort potentiel de mobilisation de P sĂ©dimentaire dans ces retenues. En condition aĂ©robie, un risque de mobilisation rĂ©sultant d’un Ă©quilibre des concentrations en P entre solutĂ© et fraction solide existe nĂ©anmoins. La dĂ©termination de valeur seuil EPC0 a soulignĂ© l’évolution du rĂŽle de puits/source du sĂ©diment vis-Ă -vis du P entre les retenues d’un mĂȘme complexe. Enfin, l’étude de la mobilitĂ© du P sĂ©dimentaire en laboratoire, suite Ă  deux cycles successifs aĂ©robies et anaĂ©robies montre que l’oscillation du potentiel d’oxydo-rĂ©duction, observĂ© dans les retenues, favorise la mobilisation du P sĂ©dimentaire. La gĂ©ochimie du Fe et la qualitĂ© de la matiĂšre organique dissoute semble ĂȘtre tous les deux impliquĂ©s dans la mobilitĂ© du P

    Sedimentary phosphorus mobility in the context of hydroelectric dam reservoirs

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    La charge interne en phosphore (P) sĂ©dimentaire stockĂ©e dans les retenues de barrages retarde la restauration du processus d’eutrophisation. Ainsi, l’étude de la mobilitĂ© du P sĂ©dimentaire dans les retenues de barrage permet d’une part de comprendre son cycle gĂ©ochimique dans ces systĂšmes, d’autre part de mieux apprĂ©hender les politiques de gestions de restauration des milieux. Cette Ă©tude met en Ă©vidence l’impact de trois barrages en cascade (Complexe de l’Age, Creuse, France) sur la distribution du P sĂ©dimentaire le long d’un continuum fluviatile. Dans les retenues Ă©tudiĂ©es, les teneurs en TP sont en moyenne de 1,59 ± 0,51 mgP/gsec et augmentent en direction des barrages. Ceci contraste avec les faibles teneurs observĂ©es dans les parties fluviatiles. Dans les rĂ©servoirs, le fractionnement chimique a montrĂ© que plus de 50% du P extrait Ă©tait associĂ© Ă  la fraction ascorbate. L’association du P avec les oxy-hydroxydes de Fe amorphes dans les particules fines des sĂ©diments accumulĂ©es prĂšs du barrage, s’avĂšre ĂȘtre le facteur majeur expliquant les variations longitudinales des teneurs en TP. De plus, ces fortes teneurs associĂ©es Ă  ces phases redox-sensibles et la mise en Ă©vidence d’un hypolimnion anoxique, rĂ©vĂšle le fort potentiel de mobilisation de P sĂ©dimentaire dans ces retenues. En condition aĂ©robie, un risque de mobilisation rĂ©sultant d’un Ă©quilibre des concentrations en P entre solutĂ© et fraction solide existe nĂ©anmoins. La dĂ©termination de valeur seuil EPC0 a soulignĂ© l’évolution du rĂŽle de puits/source du sĂ©diment vis-Ă -vis du P entre les retenues d’un mĂȘme complexe. Enfin, l’étude de la mobilitĂ© du P sĂ©dimentaire en laboratoire, suite Ă  deux cycles successifs aĂ©robies et anaĂ©robies montre que l’oscillation du potentiel d’oxydo-rĂ©duction, observĂ© dans les retenues, favorise la mobilisation du P sĂ©dimentaire. La gĂ©ochimie du Fe et la qualitĂ© de la matiĂšre organique dissoute semble ĂȘtre tous les deux impliquĂ©s dans la mobilitĂ© du P.Internal sedimentary phosphorus (P) load cause delay time in eutrophication recovery, especially in dam-reservoir systems where P stock are important. Then, the study of sedimentary P mobility in dam-reservoirs allow to better explain P geochemistry in this context and further to adapt management restauration policies. This study highlights the impact of three cascade dams (Age Complex, Creuse, France) on the distribution of sedimentary P along a fluvial continuum. In the impoundments studied, TP levels averaged 1.59 ± 0.51 mgP /g DW and increased towards dams. This contrast with the low and constant concentrations observed in the fluvial parts. In reservoirs, chemical fractionation showed that more than 50% of the extracted P was associated with the ascorbate fraction. The association of P to amorphous Fe oxi-hydroxides in the fine particles accumulated closed to the dam is the major factor explaining the longitudinal variations of the TP contents. In addition, the high levels of P associated with these redox-sensitive phases and the development of a hypoxic hypolimnion in studied reservoirs reveal the high potential for sediment P mobilization. Moreover, in aerobic conditions, a risk of mobilization resulting from an equilibrium concentration between solute and solid fraction exists. The determination of the EPC0 threshold value underlined the spatial evolution of the sink / source role of the sediment with respect to the P, between the reservoirs of the same complex. Finally, the study of sedimentary P mobility in the laboratory, following two successive aerobic and anaerobic cycles, showed that redox potential oscillation observed in the reservoirs, favors the mobilization of the sedimentary P. The geochemistry of iron and the quality of dissolved organic matter appear to be involved in the mobility of P

    Traduction et validation en langue française de l’instrument "Diabetes Knowledge Questionnaire"

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    Introduction : l’amĂ©lioration des connaissances des patients sur le diabĂšte pourrait soutenir leur adhĂ©sion au traitement, prĂ©venir les complications et favoriser la prise de dĂ©cision partagĂ©e. Les professionnels de la santĂ© ont besoin d’évaluer les connaissances des patients Ă  l’aide d’un questionnaire validĂ© dans la langue locale. Objectif : l’étude avait pour but de traduire le Diabetes Knowledge Questionnaire en français et d’évaluer les qualitĂ©s psychomĂ©triques de la version traduite. MĂ©thodes : dans cette Ă©tude transversale, les personnes diabĂ©tiques ont Ă©tĂ© recrutĂ©es dans les services de diabĂ©tologie, ainsi que dans les services de dialyse, car environ 30 % des patients dialysĂ©s sont diabĂ©tiques. Les participants diabĂ©tiques de type 1 ou 2 ont rĂ©pondu au questionnaire traduit, le questionnaire s’adressant aux deux populations, avec des questions supplĂ©mentaires pour les diabĂ©tiques de type 1. La fidĂ©litĂ© et la validitĂ© ont Ă©tĂ© Ă©valuĂ©es selon la dĂ©marche COSMIN. RĂ©sultats : l’analyse du questionnaire traduit (n = 102) a montrĂ© une bonne cohĂ©rence interne (α = 0,77), similaire au questionnaire d’origine. La suppression d’un item portant sur les autocontrĂŽles de glycĂ©mie a augmentĂ© le coefficient α Cronbach de 0,03. Discussion : malgrĂ© sa validation, le questionnaire mĂ©riterait une mise Ă  jour selon les nouvelles pratiques et recommandations mĂ©dicales, pour garantir une cohĂ©rence entre les connaissances souhaitĂ©es et les objectifs de soins visĂ©s. Conclusion : la version française du Diabetes Knowledge Questionnaire a dĂ©montrĂ© une bonne validitĂ© et fidĂ©litĂ©, et peut ĂȘtre utilisĂ©e dans la pratique et la recherche, aprĂšs la suppression de l’item n° 9
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