Activation of Glial FGFRs Is Essential in Glial Migration, Proliferation, and Survival and in Glia-Neuron Signaling during Olfactory System Development

Development of the adult olfactory system of the moth Manduca sexta depends on reciprocal interactions between olfactory receptor neuron (ORN) axons growing in from the periphery and centrally-derived glial cells. Early-arriving ORN axons induce a subset of glial cells to proliferate and migrate to form an axon-sorting zone, in which later-arriving ORN axons will change their axonal neighbors and change their direction of outgrowth in order to travel with like axons to their target areas in the olfactory (antennal) lobe. These newly fasciculated axon bundles will terminate in protoglomeruli, the formation of which induces other glial cells to migrate to surround them. Glial cells do not migrate unless ORN axons are present, axons fail to fasciculate and target correctly without sufficient glial cells, and protoglomeruli are not maintained without a glial surround. We have shown previously that Epidermal Growth Factor receptors and the IgCAMs Neuroglian and Fasciclin II play a role in the ORN responses to glial cells. In the present work, we present evidence for the importance of glial Fibroblast Growth Factor receptors in glial migration, proliferation, and survival in this developing pathway. We also report changes in growth patterns of ORN axons and of the dendrites of olfactory (antennal lobe) neurons following blockade of glial FGFR activation that suggest that glial FGFR activation is important in reciprocal communication between neurons and glial cells

Roles of Specific Membrane Lipid Domains in EGF Receptor Activation and Cell Adhesion Molecule Stabilization in a Developing Olfactory System

BACKGROUND:Reciprocal interactions between glial cells and olfactory receptor neurons (ORNs) cause ORN axons entering the brain to sort, to fasciculate into bundles destined for specific glomeruli, and to form stable protoglomeruli in the developing olfactory system of an experimentally advantageous animal species, the moth Manduca sexta. Epidermal growth factor receptors (EGFRs) and the cell adhesion molecules (IgCAMs) neuroglian and fasciclin II are known to be important players in these processes. METHODOLOGY/PRINCIPAL FINDINGS:We report in situ and cell-culture studies that suggest a role for glycosphingolipid-rich membrane subdomains in neuron-glia interactions. Disruption of these subdomains by the use of methyl-beta-cyclodextrin results in loss of EGFR activation, depletion of fasciclin II in ORN axons, and loss of neuroglian stabilization in the membrane. At the cellular level, disruption leads to aberrant ORN axon trajectories, small antennal lobes, abnormal arrays of olfactory glomerul, and loss of normal glial cell migration. CONCLUSIONS/SIGNIFICANCE:We propose that glycosphingolipid-rich membrane subdomains (possible membrane rafts or platforms) are essential for IgCAM-mediated EGFR activation and for anchoring of neuroglian to the cytoskeleton, both required for normal extension and sorting of ORN axons

An NADPH-Dependent Genetic Switch Regulates Plant Infection by the Rice Blast Fungus

To cause rice blast disease, the fungus Magnaporthe oryzae breaches the tough outer cuticle of the rice leaf by using specialized infection structures called appressoria. These cells allow the fungus to invade the host plant and proliferate rapidly within leaf tissue. Here, we show that a unique NADPH-dependent genetic switch regulates plant infection in response to the changing nutritional and redox conditions encountered by the pathogen. The biosynthetic enzyme trehalose-6-phosphate synthase (Tps1) integrates control of glucose-6-phosphate metabolism and nitrogen source utilization by regulating the oxidative pentose phosphate pathway, the generation of NADPH, and the activity of nitrate reductase. We report that Tps1 directly binds to NADPH and, thereby, regulates a set of related transcriptional corepressors, comprising three proteins, Nmr1, Nmr2, and Nmr3, which can each bind NADP. Targeted deletion of any of the Nmr-encoding genes partially suppresses the nonpathogenic phenotype of a Δtps1 mutant. Tps1-dependentNmr corepressors control the expression of a set of virulence-associated genes that are derepressed during appressorium-mediated plant infection. When considered together, these results suggest that initiation of rice blast disease by M. oryzae requires a regulatory mechanism involving an NADPH sensor protein, Tps1, a set of NADP-dependent transcriptional corepressors, and the nonconsuming interconversion ofNADPHandNADPacting as signal transducer

Effects of emergency department Care Coordination Team referrals in older people presenting with a fall

Objectives: The study aims to describe the characteristics of patients presenting to an ED with a fall and evaluate multidisciplinary Care Coordination Team (CCT) referrals on patient outcomes. Methods: A single-centred retrospective analysis of electronic data at an adult tertiary hospital was performed using data from 2004 to 2009 of presentations for patients aged 65 years or over with a fall. The primary outcome measure was representation to hospital within 30 days, comparing patients referred to CCT and those not referred. Secondary outcomes were differences in demographic characteristics, mode of arrival, triage score and readmission. Results: The proportion of ED patients presenting with a fall and their mean age is stable over time. From 2006 to 2009, 5162 fallers were referred to CCT in a decreasing trend, but with increased urgency. Statistically significant predictors for being referred to CCT were increasing age, being female, arriving by ambulance, being transferred from a nursing home and higher socioeconomic category. Arrival by ambulance and a history of previous falls were associated with representation and readmission. A decreasing trend from 2006 to 2009 was seen in rate ratios and odds ratios via regression modelling for both representation and readmission in patients referred to CCT. Conclusion: Maturing of the CCT is associated with a decrease in representation and readmission rate. Over time, the CCT attended higher urgency patients associated with stable admission rates. These associations were not significant and the clinical effectiveness of ED CCTs requires further examination

Arsenal of plant cell wall degrading enzymes reflects host preference among plant pathogenic fungi

<p>Abstract</p> <p>Background</p> <p>The discovery and development of novel plant cell wall degrading enzymes is a key step towards more efficient depolymerization of polysaccharides to fermentable sugars for the production of liquid transportation biofuels and other bioproducts. The industrial fungus <it>Trichoderma reesei </it>is known to be highly cellulolytic and is a major industrial microbial source for commercial cellulases, xylanases and other cell wall degrading enzymes. However, enzyme-prospecting research continues to identify opportunities to enhance the activity of <it>T. reesei </it>enzyme preparations by supplementing with enzymatic diversity from other microbes. The goal of this study was to evaluate the enzymatic potential of a broad range of plant pathogenic and non-pathogenic fungi for their ability to degrade plant biomass and isolated polysaccharides.</p> <p>Results</p> <p>Large-scale screening identified a range of hydrolytic activities among 348 unique isolates representing 156 species of plant pathogenic and non-pathogenic fungi. Hierarchical clustering was used to identify groups of species with similar hydrolytic profiles. Among moderately and highly active species, plant pathogenic species were found to be more active than non-pathogens on six of eight substrates tested, with no significant difference seen on the other two substrates. Among the pathogenic fungi, greater hydrolysis was seen when they were tested on biomass and hemicellulose derived from their host plants (commelinoid monocot or dicot). Although <it>T. reesei </it>has a hydrolytic profile that is highly active on cellulose and pretreated biomass, it was less active than some natural isolates of fungi when tested on xylans and untreated biomass.</p> <p>Conclusions</p> <p>Several highly active isolates of plant pathogenic fungi were identified, particularly when tested on xylans and untreated biomass. There were statistically significant preferences for biomass type reflecting the monocot or dicot host preference of the pathogen tested. These highly active fungi are promising targets for identification and characterization of novel cell wall degrading enzymes for industrial applications.</p

The Amateur Sky Survey Mark III Project

The Amateur Sky Survey (TASS) is a loose confederation of amateur and professional astronomers. We describe the design and construction of our Mark III system, a set of wide-field drift-scan CCD cameras which monitor the celestial equator down to thirteenth magnitude in several passbands. We explain the methods by which images are gathered, processed, and reduced into lists of stellar positions and magnitudes. Over the period October, 1996, to November, 1998, we compiled a large database of photometric measurements. One of our results is the "tenxcat" catalog, which contains measurements on the standard Johnson-Cousins system for 367,241 stars; it contains links to the light curves of these stars as well.Comment: 20 pages, including 4 figures; additional JPEG files for Figures 1, 2. Submitted to PAS

Coordination of myeloid differentiation with reduced cell cycle progression by PU.1 Induction of microRNAs targeting cell cycle regulators and lipid anabolism

During macrophage development, myeloid progenitor cells undergo terminal differentiation coordinated with reduced cell cycle progression. Differentiation of macrophages from myeloid progenitors is accompanied by increased expression of the E26 transformation-specific transcription factor PU.1. Reduced PU.1 expression leads to increased proliferation and impaired differentiation of myeloid progenitor cells. It is not understood how PU.1 coordinates macrophage differentiation with reduced cell cycle progression. In this study, we utilized cultured PU.1- inducible myeloid cells to perform genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) analysis coupled with gene expression analysis to determine targets of PU.1 that may be involved in regulating cell cycle progression. We found that genes encoding cell cycle regulators and enzymes involved in lipid anabolism were directly and inducibly bound by PU.1 although their steady-state mRNA transcript levels were reduced. Inhibition of lipid anabolism was sufficient to reduce cell cycle progression in these cells. Induction of PU.1 reduced expression of E2f1, an important activator of genes involved in cell cycle and lipid anabolism, indirectly through microRNA 223. Next-generation sequencing identified microRNAs validated as targeting cell cycle and lipid anabolism for downregulation. These results suggest that PU.1 coordinates cell cycle progression with differentiation through induction of microRNAs targeting cell cycle regulators and lipid anabolism

Observational consequences of fine structure line optical depths on infrared spectral diagnostics

It has long been known that infrared fine structure lines of abundant ions, like the [O III] 88 micron line, can become optically thick in H II regions under certain high luminosity conditions. This could mitigate their potential as diagnostic tools, especially if the source is too dusty for optical spectroscopy to otherwise determine the system's parameters. We examined a series of photoionization calculations which were designed to push the nebulae into the limit where many IR lines should be quite optically thick. We find that radiative transfer effects do not significantly change the observed emission line spectrum. This is due to a combination of grain absorption of the hydrogen ionizing continuum and the fact that the correction for stimulated emission in these lines is large. Given these results, and the likelihood that real objects have non-thermal line broadening, it seems unlikely that line optical depth presents a problem in using these lines as diagnostics of the physical conditions or chemical composition.Comment: 16 pages, 4 figures, to be published in the February 2003 issue of the PAS