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(2005)
Nonsymbolic numerical magnitude processing skills are assumed to be fundamental to mathematical learning. Recent findings suggest that visual–spatial skills account for associations between children’s performance in visually presented nonsymbolic numerical magnitude comparison tasks and their performance in visually presented arithmetic tasks. The aim of the current study was to examine whether associations between children’s performance in visually presented tasks assessing nonsymbolic numerical magnitude processing skills and their performance in tasks assessing early mathematical skills, which do not involve visual stimulation, may also be mediated by visual–spatial skills. This line of reasoning is based on the assumption that children make use of mental visualization processes when working on tasks assessing early mathematical skills, such as knowledge of the sequence of number words, even when these tasks do not involve visual stimulation. We assessed 4- to 6-year-old children’s performance in a nonsymbolic numerical magnitude comparison task, in tasks concerning knowledge of the sequence of number words, and in a developmental test to assess visual–spatial skills. Children’s nonsymbolic numerical magnitude processing skills were found to be associated with their number word sequence skills. This association was fully mediated by interindividual differences in visual–spatial skills. The effect size of this mediation effect was small. We assume that the ability to construct mental visualizations constitutes the key factor underlying this mediation effect.
Synthesis and purification of peptide drugs for medical applications is a challenging task. The leech-derived factor hirudin is in clinical use as an alternative to heparin in anticoagulatory therapies. So far, recombinant hirudin is mainly produced in bacterial or yeast expression systems. We describe the successful development and application of an alternative protocol for the synthesis of active hirudin based on a cell-free protein synthesis approach. Three different cell lysates were compared, and the effects of two different signal peptide sequences on the synthesis of mature hirudin were determined. The combination of K562 cell lysates and the endogenous wild-type signal peptide sequence was most effective. Cell-free synthesized hirudin showed a considerably higher anti-thrombin activity compared to recombinant hirudin produced in bacterial cells.
Major depressive disorder (MDD) is a common and severe disease characterized by mood changes, somatic alterations, and often suicide. MDD is treated with antidepressants, but the molecular mechanism of their action is unknown. We found that widely used antidepressants such as amitriptyline and fluoxetine induce autophagy in hippocampal neurons via the slow accumulation of sphingomyelin in lysosomes and Golgi membranes and of ceramide in the endoplasmic reticulum (ER). ER ceramide stimulates phosphatase 2A and thereby the autophagy proteins Ulk, Beclin, Vps34/Phosphatidylinositol 3-kinase, p62, and Lc3B. Although treatment with amitriptyline or fluoxetine requires at least 12 days to achieve sphingomyelin accumulation and the subsequent biochemical and cellular changes, direct inhibition of sphingomyelin synthases with tricyclodecan-9-yl-xanthogenate (D609) results in rapid (within 3 days) accumulation of ceramide in the ER, activation of autophagy, and reversal of biochemical and behavioral signs of stress-induced MDD. Inhibition of Beclin blocks the antidepressive effects of amitriptyline and D609 and induces cellular and behavioral changes typical of MDD. These findings identify sphingolipid-controlled autophagy as an important target for antidepressive treatment methods and provide a rationale for the development of novel antidepressants that act within a few days.