616 research outputs found

    The C. elegans dosage compensation complex mediates interphase X chromosome compaction

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    Abstract Background Dosage compensation is a specialized gene regulatory mechanism which equalizes X-linked gene expression between sexes. In Caenorhabditis elegans, dosage compensation is achieved by the activity of the dosage compensation complex (DCC). The DCC localizes to both X chromosomes in hermaphrodites to downregulate gene expression by half. The DCC contains a subcomplex (condensin IDC) similar to the evolutionarily conserved condensin complexes which play fundamental roles in chromosome dynamics during mitosis and meiosis. Therefore, mechanisms related to mitotic chromosome condensation have been long hypothesized to mediate dosage compensation. However experimental evidence was lacking. Results Using 3D FISH microscopy to measure the volumes of X and chromosome I territories and to measure distances between individual loci, we show that hermaphrodite worms deficient in DCC proteins have enlarged interphase X chromosomes when compared to wild type. By contrast, chromosome I is unaffected. Interestingly, hermaphrodite worms depleted of condensin I or II show no phenotype. Therefore X chromosome compaction is specific to condensin IDC. In addition, we show that SET-1, SET-4, and SIR-2.1, histone modifiers whose activity is regulated by the DCC, need to be present for the compaction of the X chromosome territory. Conclusion These results support the idea that condensin IDC, and the histone modifications regulated by the DCC, mediate interphase X chromosome compaction. Our results link condensin-mediated chromosome compaction, an activity connected to mitotic chromosome condensation, to chromosome-wide repression of gene expression in interphase.http://deepblue.lib.umich.edu/bitstream/2027.42/109510/1/13072_2014_Article_335.pd

    Influence of substitutional disorder on the electrical transport and the superconducting properties of Fe1+z_{1+z}Te1−x−y_{1-x-y}Sex_{x}Sy_{y}

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    We have carried out an investigation of the structural, magnetic, transport and superconducting properties of Fe1+z_{1+z}Te1−x−y_{1-x-y}Sex_xSy_y ceramic compounds, for z=0z=0 and some specific Se (0≤\leq x ≤\leq 0.5) and S (0 ≤\leq y ≤\leq0.12) contents. The incorporation of Se and S to the FeTe structure produces a progressive reduction of the crystallographic parameters as well as different degrees of structural disorder associated with the differences of the ionic radius of the substituting cations. In the present study, we measure transport properties of this family of compounds and we show the direct influence of disorder in the normal and superconductor states. We notice that the structural disorder correlates with a variable range hopping conducting regime observed at temperatures T>T > 200 K. At lower temperatures, all the samples except the one with the highest degree of disorder show a crossover to a metallic-like regime, probably related to the transport of resilient-quasi-particles associated with the proximity of a Fermi liquid state at temperatures below the superconducting transition. Moreover, the superconducting properties are depressed only for that particular sample, in accordance to the condition that superconductivity is affected by disorder when the electronic localization length ξL\xi_L becomes smaller than the coherence length ξSC\xi_{SC}.Comment: 23 pages, 9 figure

    Extractability and chemical forms of radioactive cesium in designated wastes investigated in an on-site test

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    In the aftermath of the 2011 accident at Fukushima Daiichi Nuclear Power Plant (F1 hereafter), municipal solid waste (MSW) contaminated with radioactive cesium (rad-Cs hereafter) has been generated in 12 prefectures in Japan. The Japanese Minister of Environment classified MSW that contained rad-Cs in the concentration more than 8,000 Bq/kg as “designated (solid) waste (DSW hereafter), and prescribed the collection, storage and transportation procedures. When MSW containing rad-Cs was incinerated, rad-Cs was concentrated in fly ash, and the ash often fell into the category of DSW. We have investigated a technique that can reduce the volume of the rad-Cs-contaminated fly-ash by extracting rad-Cs with aqueous solvents such as water and oxalic acid and concentrating rad-Cs in a small amount of hexacyanoferrate (or ferrocyanide, designated as Fer hereafter) precipitate. Since DSW could not be transported to the outside laboratory, we have conducted on-site tests at places where DSW were generated to investigate the applicability of the extraction – precipitation technique. The present report is a summary of our most recent on-site test conducted in 2014. Also presented is the re-evaluation of the results of our past on-site test from the viewpoint of leaching of rad-Cs and heavy metals in the fly ash. An apparent decrease in leaching of rad-Cs from fly ash was observed by incinerating sewage sludge with soil. Fly ash from a melting furnace contained more water-soluble rad-Cs than that from a fluidized-bed incinerator. Some incinerator fly ash appeared to produce rad-Cs in colloidal form when extracted with oxalic acid, resulting in the lower removal of rad-Cs from the extract by Fer method. © The Editor(s) if applicable and the Author(s) 2016

    Differential Expressions of Adhesive Molecules and Proteases Define Mechanisms of Ovarian Tumor Cell Matrix Penetration/Invasion

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    Epithelial ovarian cancer is an aggressive and deadly disease and understanding its invasion mechanisms is critical for its treatment. We sought to study the penetration/invasion of ovarian tumor cells into extracellular matrices (ECMs) using a fibroblast-derived three-dimensional (3D) culture model and time-lapse and confocal imaging. Twelve ovarian tumor cells were evaluated and classified into distinct groups based on their ECM remodeling phenotypes; those that degraded the ECM (represented by OVCAR5 cells) and those that did not (represented by OVCAR10 cells). Cells exhibiting a distinct ECM modifying behavior were also segregated by epithelial- or mesenchymal-like phenotypes and uPA or MMP-2/MMP-9 expression. The cells, which presented epithelial-like phenotypes, penetrated the ECM using proteases and maintained intact cell-cell interactions, while cells exhibiting mesenchymal phenotypes modified the matrices via Rho-associated serine/threonine kinase (ROCK) in the absence of apparent cell-cell interactions. Overall, this study demonstrates that different mechanisms of modifying matrices by ovarian tumor cells may reflect heterogeneity among tumors and emphasize the need to systematically assess these mechanisms to better design effective therapies

    The diacylglycerol kinase α/Atypical PKC/β1 integrin pathway in SDF-1α mammary carcinoma invasiveness

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    Diacylglycerol kinase α (DGKα), by phosphorylating diacylglycerol into phosphatidic acid, provides a key signal driving cell migration and matrix invasion. We previously demonstrated that in epithelial cells activation of DGKα activity promotes cytoskeletal remodeling and matrix invasion by recruiting atypical PKC at ruffling sites and by promoting RCP-mediated recycling of α5β1 integrin to the tip of pseudopods. In here we investigate the signaling pathway by which DGKα mediates SDF-1α-induced matrix invasion of MDA-MB-231 invasive breast carcinoma cells. Indeed we showed that, following SDF-1α stimulation, DGKα is activated and localized at cell protrusion, thus promoting their elongation and mediating SDF-1α induced MMP-9 metalloproteinase secretion and matrix invasion. Phosphatidic acid generated by DGKα promotes localization at cell protrusions of atypical PKCs which play an essential role downstream of DGKα by promoting Rac-mediated protrusion elongation and localized recruitment of β1 integrin and MMP-9. We finally demonstrate that activation of DGKα, atypical PKCs signaling and β1 integrin are all essential for MDA-MB-231 invasiveness. These data indicates the existence of a SDF-1α induced DGKα - atypical PKC - β1 integrin signaling pathway, which is essential for matrix invasion of carcinoma cells

    Synthetic emmprin peptides with chitobiose substitution stimulate MMP-2 production by fibroblasts

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    <p>Abstract</p> <p>Background</p> <p>Emmprin, a glycoprotein containing two Ig domains, is enriched on tumor cell surfaces and stimulates matrix metalloproteinase (MMP) production by adjacent stromal cells. Its first Ig domain (ECI) contains the biologically active site. The dependence of emmprin activity on N-glycosylation is controversial. We investigated whether synthetic ECI with the shortest sugar is functionally active.</p> <p>Methods</p> <p>The whole ECI peptides carrying sugar chains, a chitobiose unit or N-linked core pentasaccharide, were synthesized by the thioester method and added to fibroblasts to examine whether they stimulate MMP-2 production.</p> <p>Results</p> <p>ECI carrying a chitobiose unit, ECI-(GlcNAc) <sub>2</sub>, but not ECI without a chitobiose unit or the chitobiose unit alone, dose-dependently stimulated MMP-2 production by fibroblasts. ECI with longer chitobiose units, ECI-[(Man)<sub>3</sub>(GlcNAc)<sub>2</sub>], also stimulated MMP-2 production, but the extent of its stimulation was lower than that of ECI-(GlcNAc)<sub>2</sub>.</p> <p>Conclusions</p> <p>Our results indicate that ECI can mimic emmprin activity when substituted with chitobiose, the disaccharide with which N-glycosylation starts.</p
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