22 research outputs found

    Identifying the roles of amino acids, alcohols and 1,2-diamines as mediators in coupling of haloarenes to arenes

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    Coupling of haloarenes to arenes has been facilitated by a diverse range of organic additives in the presence of KO(t)Bu or NaO(t)Bu since the first report in 2008. Very recently, we showed that the reactivity of some of these additives (e.g., compounds 6 and 7) could be explained by the formation of organic electron donors in situ, but the role of other additives was not addressed. The simplest of these, alcohols, including 1,2-diols, 1,2-diamines, and amino acids are the most intriguing, and we now report experiments that support their roles as precursors of organic electron donors, underlining the importance of this mode of initiation in these coupling reactions

    Comparison of methods for collecting and modeling dissimilarity data: applications to complex sound stimuli

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    Sorting procedures are frequently adopted as an alternative to dissimilarity ratings to measure the dissimilarity of large sets of stimuli in a comparatively short time. However, systematic empirical research on the consequences of this experiment-design choice is lacking. We carried out a behavioral experiment to assess the extent to which sorting procedures compare to dissimilarity ratings in terms of efficiency, reliability, and accuracy, and the extent to which data from different data-collection methods are redundant and are better fit by different distance models. Participants estimated the dissimilarity of either semantically charged environmental sounds or semantically neutral synthetic sounds. We considered free and hierarchical sorting and derived indications concerning the properties of constrained and truncated hierarchical sorting methods from hierarchical sorting data. Results show that the higher efficiency of sorting methods comes at a considerable cost in terms of data reliability and accuracy. This loss appears to be minimized with truncated hierarchical sorting methods that start from a relatively low number of groups of stimuli. Finally, variations in data-collection method differentially affect the fit of various distance models at the group-average and individual levels. On the basis of these results, we suggest adopting sorting as an alternative to dissimilarity-rating methods only when strictly necessary. We also suggest analyzing the raw behavioral dissimilarities, and avoiding modeling them with one single distance model

    Early-onset autosomal recessive cerebellar ataxia associated with retinal dystrophy: new human hotfoot phenotype caused by homozygous GRID2 deletion

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    Purpose: The aim of this study was to identify the genetic cause of early-onset autosomal recessive cerebellar ataxia associated with retinal dystrophy in a consanguineous family. Methods: An affected 6-month-old child underwent neurological and ophthalmological examinations. Genetic analyses included homozygosity mapping, copy number analysis, conventional polymerase chain reaction, Sanger sequencing, quantitative polymerase chain reaction, and whole-exome sequencing. Expression analysis of GRID2 was performed by quantitative polymerase chain reaction and immunohistochemistry. Results: A homozygous deletion of exon 2 of GRID2 (p.G1y30_Glu-81del) was identified in the proband. GRID2 encodes an ionotropic glutamate receptor known to be selectively expressed in cerebellar Purkinje cells. Here, we demonstrated GRID2 expression in human adult retina and retinal pigment epithelium. In addition, Grid2 expression was demonstrated in different stages of murine retinal development. GRID2 immunostaining was shown in murine and human retina. Whole-exome sequencing in the proband did not provide arguments for other disease-causing mutations, supporting the idea that the phenotype observed represents a single clinical entity. Conclusion: We identified GRID2 as an underlying disease gene of early-onset autosomal recessive cerebellar ataxia with retinal dystrophy, expanding the clinical spectrum of GRID2 deletion mutants. We demonstrated for the first time GRID2 expression and localization in human and murine retina, providing evidence for a novel functional role of GRID2 in the retina. Genet Med advance online publication 14 August 201
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