4,346 research outputs found

    Sleep drive reconfigures wake-promoting clock circuitry to regulate adaptive behavior

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    Circadian rhythms help animals synchronize motivated behaviors to match environmental demands. Recent evidence indicates that clock neurons influence the timing of behavior by differentially altering the activity of a distributed network of downstream neurons. Downstream circuits can be remodeled by Hebbian plasticity, synaptic scaling, and, under some circumstances, activity-dependent addition of cell surface receptors; the role of this receptor respecification phenomena is not well studied. We demonstrate that high sleep pressure quickly reprograms the wake-promoting large ventrolateral clock neurons to express the pigment dispersing factor receptor (PDFR). The addition of this signaling input into the circuit is associated with increased waking and early mating success. The respecification of PDFR in both young and adult large ventrolateral neurons requires 2 dopamine (DA) receptors and activation of the transcriptional regulator nejire (cAMP response element-binding protein [CREBBP]). These data identify receptor respecification as an important mechanism to sculpt circuit function to match sleep levels with demand

    Molecular mechanisms linking wound inflammation and fibrosis: knockdown of osteopontin leads to rapid repair and reduced scarring

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    Previous studies of tissue repair have revealed osteopontin (OPN) to be up-regulated in association with the wound inflammatory response. We hypothesize that OPN may contribute to inflammation-associated fibrosis. In a series of in vitro and in vivo studies, we analyze the effects of blocking OPN expression at the wound, and determine which inflammatory cells, and which paracrine factors from these cells, may be responsible for triggering OPN expression in wound fibroblasts. Delivery of OPN antisense oligodeoxynucleotides into mouse skin wounds by release from Pluronic gel decreases OPN protein levels at the wound and results in accelerated healing and reduced granulation tissue formation and scarring. To identify which leukocytic lineages may be responsible for OPN expression, we cultured fibroblasts in macrophage-, neutrophil-, or mast cell–conditioned media (CM), and found that macrophage- and mast cell–secreted factors, specifically platelet-derived growth factor (PDGF), induced fibroblast OPN expression. Correspondingly, Gleevec, which blocks PDGF receptor signaling, and PDGF-Rβ–neutralizing antibodies, inhibited OPN induction by macrophage-CM. These studies indicate that inflammation-triggered expression of OPN both hinders the rate of repair and contributes to wound fibrosis. Thus, OPN and PDGF are potential targets for therapeutic modulation of skin repair to improve healing rate and quality

    Accurate Realizations of the Ionized Gas in Galaxy Clusters: Calibrating Feedback

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    Using the full, three-dimensional potential of galaxy cluster halos (drawn from an N-body simulation of the current, most favored cosmology), the distribution of the X-ray emitting gas is found by assuming a polytropic equation of state and hydrostatic equilibrium, with constraints from conservation of energy and pressure balance at the cluster boundary. The resulting properties of the gas for these simulated redshift zero clusters (the temperature distribution, mass-temperature and luminosity-temperature relations, and the gas fraction) are compared with observations in the X-ray of nearby clusters. The observed properties are reproduced only under the assumption that substantial energy injection from non-gravitational sources has occurred. Our model does not specify the source, but star formation and AGN may be capable of providing this energy, which amounts to 3 to 5 x10^{-5} of the rest mass in stars (assuming ten percent of the gas initially in the cluster forms stars). With the method described here it is possible to generate realistic X-ray and Sunyaev-Zel'dovich cluster maps and catalogs from N-body simulations, with the distributions of internal halo properties (and their trends with mass, location, and time) taken into account.Comment: Matches ApJ published version; 30 pages, 7 figure

    Arabidopsis nucleolar protein database (AtNoPDB)

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    The Arabidopsis Nucleolar Protein Database (http://bioinf.scri.sari.ac.uk/cgi-bin/atnopdb/home) provides information on 217 proteins identified in a proteomic analysis of nucleoli isolated from Arabidopsis cell culture. The database is organized on the basis of the Arabidopsis gene identifier number. The information provided includes protein description, protein class, whether or not the plant protein has a homologue in the most recent human nucleolar proteome and the results of reciprocal BLAST analysis of the human proteome. In addition, for one-third of the 217 Arabidopsis nucleolar proteins, localization images are available from analysis of full-length cDNA–green fluorescent protein (GFP) fusions and the strength of signal in different parts of the cell—nucleolus, nucleolus-associated structures, nucleoplasm, nuclear bodies and extra-nuclear—is provided. For each protein, the most likely human and yeast orthologues, where identifiable through BLASTX analysis, are given with links to relevant information sources

    Synthesis and characterisation of an N-heterocyclic carbene with spatially-defined steric impact

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    The synthesis and co-ordination chemistry of a new ‘bulky yet flexible’ N-heterocyclic carbene (“IPaul”) is reported. This carbene has spatially-defined steric impact; steric maps show that two quadrants are very bulky while the other two are quite open. The electronic properties of this carbene are very similar to those of other 1,3-diarylimidazol-2-ylidenes. Copper, silver, iridium, and nickel complexes of the new ligand have been prepared. In solution, the ligand adopts two different conformations, while X-ray crystallographic analyses of the transition metal complexes suggest that the syn-conformer is preferred in the solid state due to intermolecular interactions. The copper complex of this new ligand has been shown to be highly-active in the hydrosilylation of carbonyl compounds, when compared to the analogous IPr, IMes, IPr* and IPr*OMe complexes

    Long-lived Five-Coordinate Platinum(IV) Intermediates : regiospecific C-C coupling

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    Three different phosphine derivatives of doubly cyclometallated diphenypyridine complexes of Pt(II), 1, were reacted with methyliodide to give octahedral Pt(IV) complexes, 2, as two isomers. Treatment of either isomer of complexes 2 with AgBF4, to abstract iodide, gave long-lived five-coordinate complexes 3, which could be trapped as pyridine adducts. Complexes 3 underwent a C-C coupling reaction, at a rate that depended on phosphine size, to give a methyl group attached to the original diphenylpyridine. Recylometallation was then performed and the cycle of reactions was repeated to give a diphenylpyridine doubly methylated on only one phenyl, with complete regiospecificity. NMR was used to demonstrate the geometry of all complexes in solution, with multiple Xray crystal structures confirming these assignments
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