The generation of new neurons from neural stem cells in the adult hippocampal dentate gyrus contributes to learning and mood regulation. To sustain hippocampal neurogenesis throughout life, maintenance of the neural stem cell pool has to be tightly controlled. We found that the Notch/RBPJκ-signaling pathway is highly active in neural stem cells of the adult mouse hippocampus. Conditional inactivation of RBPJκ in neural stem cells in vivo resulted in increased neuronal differentiation of neural stem cells in the adult hippocampus at an early time point and depletion of the Sox2-positive neural stem cell pool and suppression of hippocampal neurogenesis at a later time point. Moreover, RBPJκ-deficient neural stem cells displayed impaired self-renewal in vitro and loss of expression of the transcription factor Sox2. Interestingly, we found that Notch signaling increases Sox2 promoter activity and Sox2 expression in adult neural stem cells. In addition, activated Notch and RBPJκ were highly enriched on the Sox2 promoter in adult hippocampal neural stem cells, thus identifying Sox2 as a direct target of Notch/RBPJκ signaling. Finally, we found that overexpression of Sox2 can rescue the self-renewal defect in RBPJκ-deficient neural stem cells. These results identify RBPJκ-dependent pathways as essential regulators of adult neural stem cell maintenance and suggest that the actions of RBPJκ are, at least in part, mediated by control of Sox2 expression.

SUMMARY Ligand-mediated dimerization has emerged as a universal mechanism of growth factor receptor activation. Recent structural studies have shown that neurotrophins interact with dimers of the p75 neurotrophin receptor (p75NTR), but the actual mechanism of receptor activation has remained elusive. Here we show that p75NTR forms disulphide-linked dimers independently of neurotrophin binding through the highly conserved Cys257 in its transmembrane domain. Mutation of Cys257 abolished neurotrophin-dependent receptor activity but did not affect downstream signaling by the p75NTR/NgR/Lingo-1 complex in response to MAG, indicating the existence of distinct, ligand-specific activation mechanisms for p75NTR. FRET experiments revealed a close association of p75NTR intracellular domains that was transiently disrupted by conformational changes induced upon NGF binding. Although mutation of Cys257 did not alter the oligomeric state of p75NTR, the mutant receptor was no longer able to propagate conformational changes to the cytoplasmic domain upon ligand binding. We propose that neurotrophins activate p75NTR by a novel mechanism involving rearrangement of disulphide-linked receptor subunits.

The dentate gyrus of the hippocampus is an exception to a 'neurogenesis-unfriendly' environment of the adult brain. New functional neurons generated in this region contribute to learning and mood regulation, and thus represent a unique form of neural plasticity. The rate of hippocampal neurogenesis significantly changes on physiological or pathological influences, such as physical activity, environmental enrichment, stress, and aging. We suggest that epigenetic mechanisms could be sensors of environmental changes and fine modulators of adult hippocampal neurogenesis. Here, we examine the role of DNA methylation and methylation of core histones mediated by the Polycomb and Trithorax complexes in the regulation of adult neurogenesis. Given the recent surprising discovery of dynamic and reversible DNA methylation in the hippocampus, we speculate regarding its regulation and its role in adult neurogenesis.

NTRactivation by neurotrophins, and reveal a genetic approach to generate gain-of-function receptor variants with distinct functional profiles.

In this paper, full and hollow fibers having round and trilobal cross-sectional shapes were produced in equal manufacturing conditions and bending, drapability and crease recovery behaviors of the woven fabrics produced from these fibers were investigated. The bending rigidities of the fabrics produced from hollow fibers were higher than the bending rigidities of the fabrics produced from full fibers. The highest bending rigidities were obtained in fabrics produced from hollow round fibers. The bending rigidities and drapabilities of the fabrics produced from fibers of similar cross-sectional shapes were in close relation with each other. The fabrics produced from full fibers had higher drapabilities than those produced from hollow fibers. The fabrics produced from full fibers had higher crease recovery angles than those produced from hollow fibers. Considering that the construction properties of the fabrics were kept constant, it could be concluded that the differences among the properties of the fabrics which were produced from full and hollow fibers (for both round and trilobal cross-sectional shapes) basically emerged from the very high differences between moments of inertia of full and hollow cross sections. It was also considered that another factor which caused differences between the fabric properties was the different bulkiness of the fibers and also the different bulkiness of the yarns with the same counts. The best results could be obtained with round and trilobal full fibers at fabrics in which drapability and crease recovery are desired.

The effects of the fiber cross-sectional shape on the structure and properties of polyester fibers were investigated. Fully drawn yarn (FDY) polyester fibers (167 dtex and 48 filaments) were produced under the same spinning conditions used in a spinning plant. The only difference between the fibers was their cross-sectional shapes. Four different cross-sectional shapes were chosen for the experimental work: round, hollow-round, trilobal, and hollow-trilobal. The crystallinity and values of the maximum stress, maximum strain, modulus, yield stress, shrinkage in boiling water, and unevenness of the fibers were determined. The difference in the cross-sectional shapes influenced the modulus, maximum strain, yield stress, and shrinkage in boiling water. No effects on the crystallinity and maximum stress were observed. The results suggested that the hollow fibers had higher amorphous orientation than the full fibers. The hollow-round fiber had the highest unevenness value.

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