Showing papers by "Neil R. Smalheiser published in 2002"

Reelin function in neural stem cell biology

Abstract: In the adult brain, neural stem cells (NSC) must migrate to express their neuroplastic potential. The addition of recombinant reelin to human NSC (HNSC) cultures facilitates neuronal retraction in the neurospheroid. Because we detected reelin, α3-integrin receptor subunits, and disabled-1 immunoreactivity in HNSC cultures, it is possible that integrin-mediated reelin signal transduction is operative in these cultures. To investigate whether reelin is important in the regulation of NSC migration, we injected HNSCs into the lateral ventricle of null reeler and wild-type mice. Four weeks after transplantation, we detected symmetrical migration and extensive neuronal and glial differentiation of transplanted HNSCs in wild-type, but not in reeler mice. In reeler mice, most of the injected HNSCs failed to migrate or to display the typical differentiation pattern. However, a subpopulation of transplanted HNSCs expressing reelin did show a pattern of chain migration in the reeler mouse cortex. We also analyzed the endogenous NSC population in the reeler mouse using bromodeoxyuridine injections. In reeler mice, the endogenous NSC population in the hippocampus and olfactory bulb was significantly reduced compared with wild-type mice; in contrast, endogenous NSCs expressed in the subventricular zonewere preserved. Hence, it seems likely that the lack of endogenous reelin may have disrupted the migration of the NSCs that had proliferated in the SVZ. We suggest that a possible inhibition of NSC migration in psychiatric patients with a reelin deficit may be a potential problem in successful NSC transplantation in these patients.

Informatics and hypothesis‐driven research

Abstract: of data, but rather as providing significant ‘added value’. Consider a commercial database consisting of credit-card transactions: its purpose is to keep track of individual accounts, and most of the queries to the database are specific, focused and initiated individually. In contrast, automated data-mining techniques permit the same database to be characterised in terms of significant large-scale correlations that provide a rich array of market research data. More importantly, one can search on an ongoing basis for anomalous patterns of activity that raise the possibility of fraud; in fact, a commercial database that does not carry out such automated ‘data-driven discovery’ might even be considered negligent. I suggest that research databases that are populated and analysed according to specific