Effects of grinding on the surface integrity of an austenitic stainless steel

International audienc

Classification of Human Chromosome 21 Gene-Expression Variations in Down Syndrome: Impact on Disease Phenotypes

Down syndrome caused by chromosome 21 trisomy is the most common genetic cause of mental retardation in humans. Disruption of the phenotype is thought to be the result of gene-dosage imbalance. Variations in chromosome 21 gene expression in Down syndrome were analyzed in lymphoblastoid cells derived from patients and control individuals. Of the 359 genes and predictions displayed on a specifically designed high-content chromosome 21 microarray, one-third were expressed in lymphoblastoid cells. We performed a mixed-model analysis of variance to find genes that are differentially expressed in Down syndrome independent of sex and interindividual variations. In addition, we identified genes with variations between Down syndrome and control samples that were significantly different from the gene-dosage effect (1.5). Microarray data were validated by quantitative polymerase chain reaction. We found that 29% of the expressed chromosome 21 transcripts are overexpressed in Down syndrome and correspond to either genes or open reading frames. Among these, 22% are increased proportional to the gene-dosage effect, and 7% are amplified. The other 71% of expressed sequences are either compensated (56%, with a large proportion of predicted genes and antisense transcripts) or highly variable among individuals (15%). Thus, most of the chromosome 21 transcripts are compensated for the gene-dosage effect. Overexpressed genes are likely to be involved in the Down syndrome phenotype, in contrast to the compensated genes. Highly variable genes could account for phenotypic variations observed in patients. Finally, we show that alternative transcripts belonging to the same gene are similarly regulated in Down syndrome but sense and antisense transcripts are not

Ternary phase diagram of ketamine ((R,S)-2-(2-chlorophenyl)-2methylaminocyclohexanone) in ethanol and preliminary studies aiming at Enantioselective Crystallization of S-ketamine

Crystallization is an important industrial-scale process for the purification of enantiomers that depends on a phase diagram. In this work, the ternary phase diagram of R- and S-ketamine in ethanol was determined. The eutectic point indicated that crystallization of pure enantiomers from solutions containing more than 75% of the desired enantiomer is feasible. Solubility studies showed the feasibility of using temperature control to conduct the process. Batch crystallization of ketamine (S/R:80/20) solutions at 25ºC provided the isolation of S-ketamine (purity of 100%) with a yield from 65 to 70% and a productivity of 6.5 g/(lh)

BDNF and DYRK1A are variable and inversely correlated in lymphoblastoid cell lines from Down Syndrome patients

Down syndrome or trisomy 21 is the most common genetic disorder leading to mental retardation. One feature is impaired short- and long-term spatial memory, which has been linked to altered brain-derived neurotrophic factor (BDNF) levels. Mouse models of Down syndrome have been used to assess neurotrophin levels, and reduced BDNF has been demonstrated in brains of adult transgenic mice overexpressing Dyrk1a, a candidate gene for Down syndrome phenotypes. Given the link between DYRK1A overexpression and BDNF reduction in mice, we sought to assess a similar association in humans with Down syndrome. To determine the effect of DYRK1A overexpression on BDNF in the genomic context of both complete trisomy 21 and partial trisomy 21, we used lymphoblastoid cell lines from patients with complete aneuploidy of human chromosome 21 (three copies of DYRK1A) and from patients with partial aneuploidy having either two or three copies of DYRK1A. Decreased BDNF levels were found in lymphoblastoid cell lines from individuals with complete aneuploidy as well as those with partial aneuploidies conferring three DYRK1A alleles. In contrast, lymphoblastoid cell lines from individuals with partial trisomy 21 having only two DYRK1A copies displayed increased BDNF levels. A negative correlation was also detected between BDNF and DYRK1A levels in lymphoblastoid cell lines with complete aneuploidy of human chromosome 21. This finding indicates an upward regulatory role of DYRK1A expression on BDNF levels in lymphoblastoid cell lines and emphasizes the role of genetic variants associated with psychiatric disorders.Asma Tlili, Alexander Hoischen, Clémentine Ripoll, Eva Benabou, Anne Badel, Anne Ronan, Renaud Touraine, Yann Grattau, Samantha Stora, Bregje van Bon, Bert de Vries, Björn Menten, Nele Bockaert, Joseph Gecz, Stylianos E. Antonarakis, Dominique Campion, Marie-Claude Potier, Henri Bléhaut, Jean-Maurice Delabar and Nathalie Jane