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Standard cell culture systems impose environmental oxygen (O(2)) levels of 20%, whereas actual tissue O(2) levels in both developing and adult brain are an order of magnitude lower. To address whether proliferation and differentiation of CNS precursors in vitro are influenced by the O(2) environment, we analyzed embryonic day 12 rat mesencephalic precursor(More)
We report on generation of dopamine neurons from long-term cultures of human fetal mesencephalic precursor cells. These CNS precursor cells were successfully expanded in vitro using the mitogens epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2). Incubation of these cultures in 3% atmospheric oxygen resulted in higher cellular yields than(More)
Isolated neural crest stem cells (NCSCs) differentiate to autonomic neurons in response to bone morphogenetic protein 2 (BMP2) in clonal cultures, but these neurons do not express sympathoadrenal (SA) lineage markers. Whether this reflects a developmental restriction in NCSCs or simply inappropriate culture conditions was not clear. We tested the growth and(More)
This paper aims to bridge progress in neuroscience involving sophisticated quantitative analysis of behavior, including the use of robust control, with other relevant conceptual and theoretical frameworks from systems engineering, systems biology, and mathematics. Familiar and accessible case studies are used to illustrate concepts of robustness,(More)
Complex engineered and biological systems share protocol-based architectures that make them robust and evolvable, but with hidden fragilities to rare perturbations. Chaos, fractals, random graphs and power laws inspire a popular view of complexity in which behaviours that are typically unpredictable and fragile 'emerge' from simple interconnections among(More)
High-level, mathematically precise descriptions of the global organisation of complex metabolic networks are necessary for understanding the global structure of metabolic networks, the interpretation and integration of large amounts of biologic data (sequences, various -omics) and ultimately for rational design of therapies for disease processes. Metabolic(More)
1868 M any of the detailed mechanisms by which bacteria express genes in response to various environmental signals are well-known. The molecular players underlying these responses are part of a bacterial transcriptional regulatory network (BTN). To explore the properties and evolution of such networks and to extract general principles, biologists have(More)
In this study we present a novel imaging method that combines high resolution cerebral blood flow imaging with a highly flexible map of absolute pO 2. In vivo measurements of pO 2 in animals using phosphorescence quenching is a well established method, and is preferable over electrical probes which are inherently invasive and are limited to single point(More)