102 research outputs found

    Ydj1 governs fungal morphogenesis and stress response, and facilitates mitochondrial protein import via Mas1 and Mas2

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    We thank Zhen-Yuan Lin for help in the preparation of the AP-MS samples, and Cathy Collins for technical assistance. MDL is supported by a Sir Henry Wellcome Postdoctoral Fellowship (Wellcome Trust 096072), LEC is supported by a Canada Research Chair in Microbial Genomics and Infectious Disease and by Cana-dian Institutes of Health Research (CIHR) Grants MOP-119520 and MOP-86452. OK is supported by National Insti-tutes of Health grant 5R01GM108975. A-CG is supported by a CIHR Foundation Grant (FDN143301), Genome Cana-da Genomics Innovation Network (GIN) Node and Tech-nical Development Grants, and a Canada Research Chair in Functional Proteomics. J-PL was supported by a TD Bank Health Research Fellowship at the Lunenfeld-Tanenbaum Research Institute and by a Scholarship for the Next Gen-eration of Scientists from the Cancer Research Society. JLX is supported by a CIHR – Frederick Banting and Charles Best Canada Graduate Scholarship. The funding agencies had no role in the study design, data collection and inter-pretation, or the decision to submit the work for publication.Peer reviewedPublisher PD

    Signaling through Lrg1, Rho1 and Pkc1 Governs Candida albicans Morphogenesis in Response to Diverse Cues

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    The capacity to transition between distinct morphological forms is a key virulence trait for diverse fungal pathogens. A poignant example of a leading opportunistic fungal pathogen of humans for which an environmentally responsive developmental program underpins virulence is Candida albicans. C. albicans mutants that are defective in the transition between yeast and filamentous forms typically have reduced virulence. Although many positive regulators of C. albicans filamentation have been defined, there are fewer negative regulators that have been implicated in repression of filamentation in the absence of inducing cues. To discover novel negative regulators of filamentation, we screened a collection of 1,248 C. albicans homozygous transposon insertion mutants to identify those that were filamentous in the absence of inducing cues. We identified the Rho1 GAP Lrg1, which represses filamentous growth by stimulating Rho1 GTPase activity and converting Rho1 to its inactive, GDP-bound form. Deletion of LRG1or introduction of a RHO1 mutation that locks Rho1 in constitutively active, GTP-bound state, leads to filamentation in the absence of inducing cues. Deletion of the Rho1 downstream effector PKC1 results in defective filamentation in response to diverse host-relevant inducing cues, including serum. We further established that Pkc1 is not required to sense filament-inducing cues, but its kinase activity is critical for the initiation of filamentous growth. Our genetic analyses revealed that Pkc1 regulates filamentation independent of the canonical MAP kinase cascade. Further, although Ras1 activation is not impaired in a pkc1Δ/pkc1Δ mutant, adenylyl cyclase activity is reduced, consistent with a model in which Pkc1 functions in parallel with Ras1 in regulating Cyr1 activation. Thus, our findings delineate a signaling pathway comprised of Lrg1, Rho1 and Pkc1 with a core role in C. albicans morphogenesis, and illuminate functional relationships that govern activation of a central transducer of signals that control environmental response and virulence programs

    Dissolution of cellulose in ionic liquid–DMSO mixtures : roles of DMSO/IL ratio and the cation alkyl chain length

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    The dissolution behavior of cellulose in the mixtures of dimethyl sulfoxide (DMSO) and different ionic liquids (ILs) at 25 °C was studied. High solubility of cellulose was reached in the mixtures of ILs and DMSO at mole fractions of 1:2, 1:2, and 1:1 for 1-butyl-3-methylimidazolium acetate, 1-propyl-3-methylimidazolium acetate, and 1-ethyl-3-methylimidazolium acetate, respectively. At high DMSO/IL molar ratios (10:1–2:1), a longer alkyl chain of the IL cation led to higher cellulose solubility. However, shorter cation alkyl chains favored cellulose dissolution at 1:1. Rheological, Fourier transform infrared spectroscopy (FTIR), and nuclear magnetic resonance (NMR) measurements were used to understand cellulose dissolution. It was found out that the increase of the DMSO ratio in binary mixtures caused higher cellulose solubility by decreasing the viscosity of systems. For cations with longer alkyl chains, stronger interaction between the IL and cellulose and higher viscosity of DMSO/IL mixtures were observed. The new knowledge obtained here could be useful to the development of cost-effective solvent systems for biopolymers

    Structural disorganization of cereal, tuber and bean starches in aqueous ionic liquid at room temperature : role of starch granule surface structure

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    The structural disorganization of different starches in a 1-ethyl-3-methylimidazolium acetate ([Emim][OAc])/water mixture (1:6 mol./mol.) at room temperature (25 °C) was studied. For normal cereal starches, which have pinholes randomly dispersed on the granule surface or only in the outermost annular region (wheat starch), the aqueous ionic liquid (IL) completely destroyed the granule structure within 1–1.5 h. Pea starch (PeS) granules with cracks were destroyed by the aqueous IL within 6 h. High-amylose maize starch (HAMS), as well as potato and purple yam starches (PoS and PYS), which have a dense and thick outer granule layer, were even more resistant to the action of the solvent. Structural disorganization was accompanied by increased viscosity and controlled the binding of water molecules with starch chains. From this study, we concluded that the surface characteristics of starch granule are an important factor affecting starch structural disorganization in an aqueous IL

    Anchoring Cu 1 species over nanodiamond-graphene for semi-hydrogenation of acetylene

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    The design of cheap, non-toxic, and earth-abundant transition metal catalysts for selective hydrogenation of alkynes remains a challenge in both industry and academia. Here, we report a new atomically dispersed copper (Cu) catalyst supported on a defective nanodiamondgraphene (ND@G), which exhibits excellent catalytic performance for the selective conversion of acetylene to ethylene, i.e., with high conversion (95%), high selectivity (98%), and good stability (for more than 60 h). The unique structural feature of the Cu atoms anchored over graphene through Cu-C bonds ensures the effective activation of acetylene and easy desorption of ethylene, which is the key for the outstanding activity and selectivity of the catalyst

    The Candida albicans transcription factor Cas5 couples stress responses, drug resistance and cell cycle regulation

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    We thank Cowen lab members for helpful discussions. We also thank David Rogers (University of Tennessee) for sharing microarray analysis of the CAS5 homozygous mutant, and Li Ang (University of Macau) for assistance in optimizing the ChIP-Seq experiments. J.L.X. is supported by a Canadian Institutes of Health Research Doctoral award and M.D.L. is supported by a Sir Henry Wellcome Postdoctoral Fellowship (Wellcome Trust 096072). B.T.G. holds an Ontario Graduate Scholarship. C.B. and B.J.A. are supported by the Canadian Institutes of Health Research Foundation Grants (FDN-143264 and -143265). D.J.K. is supported by a National Institute of Allergy and Infectious Diseases grant (1R01AI098450) and J.D.L.C.D. is supported by the University of Rochester School of Dentistry and Medicine PREP program (R25 GM064133). A.S. is supported by the Creighton University and the Nebraska Department of Health and Human Services (LB506-2017-55). K.H.W. is supported by the Science and Technology Development Fund of Macau S.A.R. (FDCT; 085/2014/A2). L.E.C. is supported by the Canadian Institutes of Health Research Operating Grants (MOP-86452 and MOP-119520), the Natural Sciences and Engineering Council (NSERC) of Canada Discovery Grants (06261 and 462167), and an NSERC E.W.R. Steacie Memorial Fellowship (477598).Peer reviewedPublisher PD

    PoxA, YjeK and Elongation Factor P Coordinately Modulate Virulence and Drug Resistance in \u3cem\u3eSalmonella enterica\u3c/em\u3e

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    We report an interaction between poxA, encoding a paralog of lysyl tRNA-synthetase, and the closely linked yjeK gene, encoding a putative 2,3-ÎČ-lysine aminomutase, that is critical for virulence and stress resistance in Salmonella enterica. Salmonella poxA and yjeK mutants share extensive phenotypic pleiotropy, including attenuated virulence in mice, an increased ability to respire under nutrient-limiting conditions, hypersusceptibility to a variety of diverse growth inhibitors, and altered expression of multiple proteins, including several encoded on the SPI-1 pathogenicity island. PoxA mediates posttranslational modification of bacterial elongation factor P (EF-P), analogous to the modification of the eukaryotic EF-P homolog, eIF5A, with hypusine. The modification of EF-P is a mechanism of regulation whereby PoxA acts as an aminoacyl-tRNA synthetase that attaches an amino acid to a protein resembling tRNA rather than to a tRNA

    A Peptide Derived from the Intercellular Adhesion Molecule-2 Regulates the Avidity of the Leukocyte Integrins CD11b/CD18 and CDllc/CD18

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    ÎČ2 integrin (CDlla,b,c/CD18)-mediated cell adhesion is required for many leukocyte functions. Under normal circumstances, the integrins are nonadhesive, and become adhesive for their cell surface ligands, the intercellular adhesion molecules (ICAMs), or soluble ligands such as fibrinogen and iC3b, when leukocytes are activated. Recently, we defined a peptide derived from ICAM-2, which specifically binds to purified CDlla/CD18. Furthermore, this peptide strongly induces T cell aggregation mainly mediated by CDlla/CD18-ICAM-1 interaction, and natural killer cell cytotoxicity. In the present study, we show that the same ICAM-2 peptide also avidly binds to purified CDllb/CD18, but not to CDllc/CD18. This binding can be blocked by the CD1 lb antibody OKM10. The peptide strongly stimulates CDllb/CD18-ICAM-l-mediated cell aggregations of the monocytic cell lines THP-1 and U937. The aggregations are energy and divalent cation-dependent. The ICAM-2 peptide also induces CDllb/CD18 and CDllc/CD18-mediated binding of THP-1 cells to fibrinogen and iC3b coated on plastic. These findings indicate that in addition to induction of CDlla/CD18- mediated cell adhesion, the ICAM-2 peptide may also serve as a "trigger" for high avidity ligand binding of other ÎČ2 integrins

    Tin Assisted Fully Exposed Platinum Clusters Stabilized on Defect-Rich Graphene for Dehydrogenation Reaction

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    Tin assisted fully exposed Pt clusters are fabricated on the core-shell nanodiamond@graphene (ND@G) hybrid support (a-PtSn/ND@G). The obtained atomically dispersed Pt clusters, with an average Pt atom number of 3, were anchored over the ND@Gsupport by the assistance of Sn atoms as a partition agent and through the Pt-C bond between Pt clusters and defect-rich graphene nanoshell. The atomically dispersed Pt clusters guaranteed a full metal availability to the reactants, a high thermal stability, and an optimized adsorption/desorption behavior. It inhibits the side reactions and enhances catalytic performance in direct dehydrogenation of n-butane at a low temperature of 450 °C, leading to \u3e98% selectivity toward olefin products, and the turnover frequency (TOF) of a-PtSn/ND@G is approximately 3.9 times higher than that of the traditional Pt3Sn alloy catalyst supported on Al2O3 (Pt3Sn/Al2O3)

    Atomic-layered Au clusters on α-MoC as catalysts for the low-temperature water-gas shift reaction

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    The water-gas shift (WGS) reaction (where carbon monoxide plus water yields dihydrogen and carbon dioxide) is an essential process for hydrogen generation and carbon monoxide removal in various energy-related chemical operations. This equilibrium-limited reaction is favored at a low working temperature. Potential application in fuel cells also requires a WGS catalyst to be highly active, stable, and energy-efficient and to match the working temperature of on-site hydrogen generation and consumption units. We synthesized layered gold (Au) clusters on a molybdenum carbide (α-MoC) substrate to create an interfacial catalyst system for the ultralow-temperature WGS reaction. Water was activated over α-MoC at 303 kelvin, whereas carbon monoxide adsorbed on adjacent Au sites was apt to react with surface hydroxyl groups formed from water splitting, leading to a high WGS activity at low temperatures
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