10,074 research outputs found

    Major Tributaries

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    FNODE: Internal ARCInfo Numbering (default) TNODE: Internal ARCInfo Numbering (default) CODE: 1. Streams, rivers, channeled rivers 2. Inland shorelines 3. Wet sand limits 4. Canals, aqueducts, flumes, penstocks, kanats 5. Glacial limits 6. Snow field, glacier, land ice to water ice or ocean 7. Ice free limits 8. Connector

    Natalia LL - artystka neoawangardowa

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    The paper shows Natalia Lach-Lachowicz (Natalia LL) as a neo avant-garde artist whose works in a specific maximalistic way are very close to the main currents of avant-garde trends: new mediality (photography), minimalism, conceptualism, performance, bodyart, pop-art, and feminist art. The author of the article concentrates mainly on the mutual influences of conceptualism, consumptionism, and feminism in Natalia LL’s works and pays attention to the emancipatory potential of her works of the seventies and the eighties

    LL-37-induced human osteoblast cytotoxicity and permeability occurs independently of cellular LL-37 uptake through clathrin-mediated endocytosis

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    The host defense peptide LL-37 is cytotoxic for bacteria but it has also been reported to reduce host cell viability through an intracellular mechanism. LL-37-evoked cytotoxicity may be involved in the loss of bone tissue in periodontitis which is an inflammatory disease characterized by high concentrations of LL-37 observed locally in the periodontal tissue at the inflammation process. Here, we showed that LL-37 reduced human osteoblast-like MG63 cell viability assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and increased plasma membrane permeability determined by measuring intracellular Ca2+ levels and lactate dehydrogenase (LDH) release. Treatment with chlorpromazine, a well-recognized inhibitor of clathrin-mediated endocytosis, reduced cellular uptake of synthesized LL-37 b y about 30% assessed by Western blotting and ELISA, while filipin, an inhibitor of caveolin-mediated endocytosis, had no effect. The chlorpromazine-induced attenuation of LL-37 uptake was not associated with modulation of LL-37-induced cytotoxicity and LL-37-evoked plasma membrane permeability. Clathrin heavy chain 2 is a major protein of the polyhedral coat of coated pits and vesicles encoded by clathrin heavy chain like 1 gene. Down-regulation of clathrin heavy chain like 1 gene activity by siRNA reduced uptake of LL-37 but did not affect LL-37-induced cytotoxicity and permeability. Thus, we show, using both a pharmacological approach and knockdown of clathrin heavy chain like 1 expression, that LL-37-induced MG63 cell cytotoxicity and permeability occurs independently of LL-37 uptake via clathrin-mediated endocytosis

    Energy flux in isotropic turbulence under large variations of external forcing

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    We investigate the response of energy flux in isotropic turbulence to step-function like perturbation in external forcing at large length scales. From both physical experiments and direct numerical simulations, we measured the evolution of the Eulerian velocity structure functions, such as DLL(r)D_{LL}(r), DNN(r)D_{NN}(r), before and after the perturbation in forcing. In both cases, we observed the cascade of the energy excess at large scales cascade through scales to the dissipative range, which can be used to study the dynamics of the cascade, and in particular, to estimate the relevant time scales

    Electrochemical Oxidation of W(CO)4(LL): Generation, Characterization, and Reactivity of [W(CO)4(LL)]+ (LL=α-diimine ligands)

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    The electrochemistry of a series of W(CO)4(LL) complexes, where LL is an aromatic α-diimine ligand, was examined in coordinating and weakly coordinating media using several techniques. These compounds undergo metal-centred one-electron oxidations and the electrogenerated radical cations undergo a range of subsequent chemical steps, the nature of which depends on the substituents of the α-diimine ligand and the presence of coordinating species. In CH2Cl2/TBAPF6, where TBAPF6 is n-tetrabutylammonium hexaflurophosphate, the bulk oxidations are partially reversible at scan rates of 0.25 V s−1; the resulting tungsten(i) radicals react via disproportionation and loss of carbonyl, the rate constants for which were measured by double-potential step chronocoulometry. Large-amplitude a.c. voltammetry experiments suggest that the one-electron oxidized species are in equilibrium with the corresponding disproportionation products. Steric crowding of the metal centre prolongs the lifetime of the radical cations, allowing the infrared spectroelectrochemical characterization of two [W(CO)4(LL)]+ species. Electrogenerated [W(CO)4(LL)]+ cations are highly susceptible to attack by potential ligands; oxidations performed in CH3CN/TBAPF6, for example, were chemically irreversible. Kinetic studies in weakly coordinating media show that near-stoichiometric amounts of added pyridine and acetonitrile are enough to greatly diminish the reversibility of the bulk oxidations; the dominant path of the coupled chemistry depends on the ligand strength, with substitution being the major reaction with added pyridine, whereas disproportionation is favoured by the presence of acetonitrile. A reaction scheme that provides an overall framework of the reactions followed by the radical cations is presented and discussed in the context of the previously observed chemistry of the molybdenum analogues.</jats:p

    Structural and functional analysis of the pro-domain of human cathelicidin, LL-37

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    Cathelicidins form a family of small host defense peptides distinct from another class of cationic antimicrobial peptides, the defensins. They are expressed as large precursor molecules with a highly conserved pro-domain known as the cathelin-like domain (CLD). CLDs have high degrees of sequence homology to cathelin, a protein isolated from pig leukocytes and belonging to the cystatin family of cysteine protease inhibitors. In this report, we describe for the first time the X-ray crystal structure of the human CLD (hCLD) of the sole human cathelicidin, LL-37. The structure of hCLD, determined at 1.93 Å resolution, shows the cystatin-like fold and is highly similar to the structure of the CLD of the pig cathelicidin, protegrin-3. We assayed the in vitro antibacterial activities of hCLD, LL-37 and the precursor form, pro-cathelicidin (also known as hCAP18), and we found that the unprocessed protein inhibited the growth of Gramnegative bacteria with efficiencies comparable to the mature peptide, LL-37. In addition, the antibacterial activity of LL-37 was not inhibited by hCLD intermolecularly, since exogenously added hCLD had no effect on the bactericidal activity of the mature peptide. hCLD itself lacked antimicrobial function and did not inhibit the cysteine protease, cathepsin L. Our results contrast with previous reports of hCLD activity. A comparative structural analysis between hCLD and the cysteine protease inhibitor stefin A showed why hCLD is unable to function as an inhibitor of cysteine proteases. In this respect, the cystatin scaffold represents an ancestral structural platform from which proteins evolved divergently, with some losing inhibitory functions

    The modulatory effect of TLR2 on LL-37-induced human mast cells activation

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    The sole and endogenous anti-microbial peptide LL-37 is a significant effector molecule in the innate host defense system. Apart from its broadly direct anti-microbial activity, the peptide also activates mast cell in respect of allergic diseases and inflammation. On the other hand, mast cell can be activated by Toll-like receptors (TLRs) which are at the center of innate immunity. It was the aim of the study to illustrate the modulatory effect of TLR2 ligands peptidoglycan (PGN) and tripalmitoyl-S-glycero-Cys-(Lys)4 (Pam3CSK4) on LL-37 induced LAD2 cells (a human mast cell line) activation. LL-37 induced LAD2 cells degranulation and the release of IL-8. TLR2 ligands didn&apos;t induce LAD2 cells degranulation, but triggered the release of IL-8. Incubation with PGN or Pam3CSK4 significantly suppressed LL-37-induced degranulation through inhibition of calcium mobilization from LAD2 cells. Similarly, the release of IL-8 was inhibited when LAD2 cells were co-stimulated with TLR2 ligands and LL-37. Studies with inhibitors of key enzymes involved in mast cell signaling indicated that the release of IL-8 induced by TLR2 ligands and LL-37 involved the activation of the PI3K, ERK, JNK and calcineurin signaling pathways. In contrast, p38 activation down-regulated the release of IL-8 induced by TLR2 ligands and LL-37. Taken together, these observations suggest that activation of human mast cells by LL-37 could be modified by TLR2 ligands and the function of human mast cells could be switched from allergic reactions to innate immune response. (C) 2016 Elsevier Inc. All rights reserved.National Natural Science Foundation of China [81271755, 81371737]; Guangdong Natural Science Foundation [2014A030313708]; Shenzhen Research Grant [CXZZ20140416144209739, JCYJ20130329110752142, KQCX20120803145850990]SCI(E)[email protected]; [email protected]

    The phaeochromycins from streptomyces strain LL-P018: from taxonomy to novelties of biosynthesis

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    The phaeochromycins are a newly discovered family of aromatic polyketides produced by Streptomyces strain LL-P018. The novel phaeochromycins A and C are of medical interest as they have inhibitory activity against MK-2, a kinase involved in the inflammatory response. The phaeochromycins are structurally similar to actinomycete secondary shunt metabolites derived from the actinorhodin and enterocin biosynthetic pathways. Because these phaeochromycins show promise as potential anti-inflammatory therapeutic agents, further knowledge of their biosynthesis and the taxonomy of the producing organism was sought. Strain LL-P018 was identified taxonomically using a combination of traditional and molecular techniques. Analyses of morphology, physiology, 16S ribosomal RNA (16SrRNA) sequence, and ribosomal polymerase β- subunit (rpoB) gene sequence were used to identify LL-P018 as a strain of Streptomyces phaeochromogenes. New methods for strain comparison by combining genetic fingerprints and metabolite profiles in a single comparison were developed to assess strain variation between strain LL-P018 and closely related organisms. This approach also clarified relationships between multiple "types" and other published strains of S. phaeochromogenes and Streptomyces ederensis. Alnumycin, an additional aromatic polyketide which has structural similarities to the phaeochromycins, was produced by strain LL-P018 in liquid culture media. Genomic analysis of strain LL-P018 revealed the presence of a type II polyketide synthase gene cluster. Gene disruption experiments determined this pathway to be responsible for both phaeochromycin and alnumycin biosynthesis, suggesting that the phaeochromycins may be intermediates or shunt products in alnumycin biosynthesis. This thesis describes a novel taxonomic approach to classification which integrates data from prior genetic and metabolic assessments into a single combined comparison. The S. phaeochromogenes type strain is defined, and taxonomic status of the species S. ederensis is clarified. New insights of phaeochromycin biosynthesis are revealed by cultural and genetic studies of Streptomyces strain LL-P018.Ph. D.Includes bibliographical references

    Human host defense peptide LL-37 prevents bacterial biofilm formation

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    The ability to form biofilms is a critical factor in chronic infections by Pseudomonas aeruginosa and has made this bacterium a model organism with respect to biofilm formation. This study describes a new, previously unrecognized role for the human cationic host defense peptide LL-37. In addition to its key role in modulating the innate immune response and weak antimicrobial activity, LL-37 potently inhibited the formation of bacterial biofilms in vitro. This occurred at the very low and physiologically meaningful concentration of 0.5 μg/ml, far below that required to kill or inhibit growth (MIC = 64 μg/ml). LL-37 also affected existing, pregrown P. aeruginosa biofilms. Similar results were obtained using the bovine neutrophil peptide indolicidin, but no inhibitory effect on biofilm formation was detected using subinhibitory concentrations of the mouse peptide CRAMP, which shares 67% identity with LL-37, polymyxin B, or the bovine bactenecin homolog Bac2A. Using microarrays and follow-up studies, we were able to demonstrate that LL-37 affected biofilm formation by decreasing the attachment of bacterial cells, stimulating twitching motility, and influencing two major quorum sensing systems (Las and Rhl), leading to the downregulation of genes essential for biofilm development.Full Tex
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