The neural stem cell microenvironment

In mammals, neural stem cells appear early in development and remain active within the central nervous system for the whole life duration of the organism. During this developmental process they assume different cellular morphologies and reside within changing microenvironments whilst retaining the basic properties of a stem cell: multipotentiality and the ability to self renew. In this chapter, the basic morphological characteristics of neural stem cells will be reviewed, along with the fundamental structural components and signalling molecules of their microenvironments. In early neural development, when the patterning of the nervous system is established, neural stem cells are called neuroepithelial cells; they are situated among other neuroepithelial cells and they are exposed to various signals such as retinoic acid, sonic hedgehog and fibroblast growth factors. When neurogenesis commences, stem cells are transformed to radial glial cells and the complexity of their microenvironment increases due to the emergence of various types of neuronal progenitors, differentiated cells and extracellular signaling molecules. Finally, during adulthood, neural stem cells assume astroglial morphology and reside in specific microenvironments that are called neurogenic niches; small neurogenic islands where neurons and glia are continuously generated under the control of mechanisms largely similar to those operating during embryonic development

Oscillations in the expression of a self-repressed gene induced by a slow transcriptional dynamics

We revisit the dynamics of a gene repressed by its own protein in the case where the transcription rate does not adapt instantaneously to protein concentration but is a dynamical variable. We derive analytical criteria for the appearance of sustained oscillations and find that they require degradation mechanisms much less nonlinear than for infinitely fast regulation. Deterministic predictions are also compared with stochastic simulations of this minimal genetic oscillator

Oscillations in the expression of a self-repressed gene induced by a slow transcriptional dynamics

We revisit the dynamics of a gene repressed by its own protein in the case where the transcription rate does not adapt instantaneously to protein concentration but is a dynamical variable. We derive analytical criteria for the appearance of sustained oscillations and find that they require degradation mechanisms much less nonlinear than for infinitely fast regulation. Deterministic predictions are also compared with stochastic simulations of this minimal genetic oscillator

Evaluating the Equilibrium Welfare Impacts of the 1990 Clean Air Act Amendments in the Los Angeles Area

This dissertation develops a discrete choice equilibrium model to evaluate the benefits of the air quality improvements that occurred in the Los Angeles area following the 1990 Clean Air Act Amendments (CAAA). Large improvements in air quality will change the desirability of different neighborhoods, disrupting the equilibrium of the housing market. The discrete choice equilibrium approach accounts for the fact that air quality improvements brought about by the 1990 CAAA will change housing choices and prices. The dissertation makes two empirical contributions to public economics. First, the study provides the first application of the discrete choice equilibrium framework (Anas, 1982, Bayer et al., 2005) to the valuation of large environmental changes. Second, the study provides new evidence for the distributional benefits of the 1990 CAAA in the Los Angeles area. Households' location choices are modeled according to the random utility framework of McFadden (1978) and the differentiated product specification of Berry, Levinsohn and Pakes (1995). The model is estimated with public-use household microdata from the 1990 U.S. Census. Findings suggest that the air quality improvements that occurred in the Los Angeles area between 1990 and 2000 provided an average equilibrium welfare benefit of $1,800 to households. In contrast, average benefits are$1,400 when equilibrium price effects are not accounted, demonstrating that ignoring equilibrium effects will likely underestimate the benefits of large environmental changes. We find that the equilibrium welfare impacts of the 1990 CAAA in the Los Angeles area varied significantly across income groups. Households in the highest income quartile experienced equilibrium benefits of approximately $3,600 as compared to only$400 for households in the lowest income quartile. We also find that ignoring equilibrium adjustments in housing prices can significantly alter the distribution of relative welfare gains (i.e. welfare gains as a proportion of household income) across households. Indeed, welfare impacts that do not account for equilibrium adjustments suggest that high-income households experience larger relative welfare gains compared to low-income households. However, when accounting for equilibrium adjustments, we find that the distribution of relative welfare gains from the 1990 CAAA is fairly even across income groups

The late response of rat subependymal zone stem and progenitor cells to stroke is restricted to directly affected areas of their niche

Ischaemia leads to increased proliferation of progenitors in the subependymal zone (SEZ) neurogenic niche of the adult brain and to generation and migration of newborn neurons. Here we investigated the spatiotemporal characteristics of the mitotic activity of adult neural stem and progenitor cells in the SEZ during the sub-acute and chronic post-ischaemic phases. Ischaemia was induced by performing a 1 h unilateral middle cerebral artery occlusion (MCAO) and tissue was collected 4/5 weeks and 1 year after the insult. Neural stem cells (NSCs) responded differently from their downstream progenitors to MCAO, with NSCs being activated only transiently whilst progenitors remain activated even at 1 year post-injury. Importantly, mitotic activation was observed only in the affected areas of the niche and specifically in the dorsal half of the SEZ. Analysis of the topography of mitoses, in relation to the anatomy of the lesion and to the position of ependymal cells and blood vessels, suggested an interplay between lesion-derived recruiting signals and the local signals that normally control proliferation in the chronic post-ischaemic phase

Drosophila embryos as model systems for monitoring bacterial infection in real time.

Journal ArticleResearch Support, Non-U.S. Gov'tDrosophila embryos are well studied developmental microcosms that have been used extensively as models for early development and more recently wound repair. Here we extend this work by looking at embryos as model systems for following bacterial infection in real time. We examine the behaviour of injected pathogenic (Photorhabdus asymbiotica) and non-pathogenic (Escherichia coli) bacteria and their interaction with embryonic hemocytes using time-lapse confocal microscopy. We find that embryonic hemocytes both recognise and phagocytose injected wild type, non-pathogenic E. coli in a Dscam independent manner, proving that embryonic hemocytes are phagocytically competent. In contrast, injection of bacterial cells of the insect pathogen Photorhabdus leads to a rapid 'freezing' phenotype of the hemocytes associated with significant rearrangement of the actin cytoskeleton. This freezing phenotype can be phenocopied by either injection of the purified insecticidal toxin Makes Caterpillars Floppy 1 (Mcf1) or by recombinant E. coli expressing the mcf1 gene. Mcf1 mediated hemocyte freezing is shibire dependent, suggesting that endocytosis is required for Mcf1 toxicity and can be modulated by dominant negative or constitutively active Rac expression, suggesting early and unexpected effects of Mcf1 on the actin cytoskeleton. Together these data show how Drosophila embryos can be used to track bacterial infection in real time and how mutant analysis can be used to genetically dissect the effects of specific bacterial virulence factors.Wellcome TrustBBSR

Authentication of cow feeding and geographic origin on milk using visible and near-infrared spectroscopy.

International audience; The ability of near-infrared spectroscopy to trace cow feeding systems and farming altitude was tested on 486 bulk milk samples from France and northwestern Italy. Milks were grouped into feeding systems according to the main forage in the diet. Partial least square discriminant analysis correctly classified 95.5, 91.5, and 93.3% of pasture versus maize silage, hay, and fermented herbage feeding systems, respectively. Discrimination was slightly less successful when diets with large proportions of the nondominant forage were included in each group. Near-infrared spectroscopy correctly discriminated no-pasture from pasture milk, even with only 30% of pasture in the diet (5.4% cross-validation error), and the error stabilized when pasture exceeded 70% (2.5% error). Near-infrared spectroscopy did not reliably trace milk geographic origin when the feeding system effect was isolated from the altitude effect. These findings may be usefully exploited for the authentication of dairy products

Pyrosequencing the transcriptome of the greenhouse whitefly, Trialeurodes vaporariorum reveals multiple transcripts encoding insecticide targets and detoxifying enzymes.

Published onlineJournal ArticleResearch Support, Non-U.S. Gov'tBACKGROUND: The whitefly Trialeurodes vaporariorum is an economically important crop pest in temperate regions that has developed resistance to most classes of insecticides. However, the molecular mechanisms underlying resistance have not been characterised and, to date, progress has been hampered by a lack of nucleotide sequence data for this species. Here, we use pyrosequencing on the Roche 454-FLX platform to produce a substantial and annotated EST dataset. This 'unigene set' will form a critical reference point for quantitation of over-expressed messages via digital transcriptomics. RESULTS: Pyrosequencing produced around a million sequencing reads that assembled into 54,748 contigs, with an average length of 965 bp, representing a dramatic expansion of existing cDNA sequences available for T. vaporariorum (only 43 entries in GenBank at the time of this publication). BLAST searching of non-redundant databases returned 20,333 significant matches and those gene families potentially encoding gene products involved in insecticide resistance were manually curated and annotated. These include, enzymes potentially involved in the detoxification of xenobiotics and those encoding the targets of the major chemical classes of insecticides. A total of 57 P450s, 17 GSTs and 27 CCEs were identified along with 30 contigs encoding the target proteins of six different insecticide classes. CONCLUSION: Here, we have developed new transcriptomic resources for T. vaporariorum. These include a substantial and annotated EST dataset that will serve the community studying this important crop pest and will elucidate further the molecular mechanisms underlying insecticide resistance.CASE PhD studentship BBSRCBayer CropScienceRothamsted Researc