193 research outputs found

    Relation between Preference for Local or Global Brands and Various Demographic Features of Consumer

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    Now a days, dilemma of choosing between local and global brands is faced while purchasing most of the goods be it be a needle or a sophisticated machinery. Good quality and affordable prices of goods of global brands are overpowering the local brands. It is seen that young generation is getting very much inclined towards the global brands and gradually local brands are finding it difficult to survive in market. Along with age many other factors are also responsible for this phenomenon. In this situation a study on various factors which are related with preference for local or global brands is need of the hour. For the purpose of study a questionnaire was developed and sent to respondents in order to find out whether actually there is any relationship between demographic factors of respondents and their choice between branded and local goods. On the bases of survey it was found out that, actually there is a relation between demographic factors of respondents and their choice between local and branded goods to a large extent

    Structural elements of an NRPS cyclization domain and its intermodule docking domain

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    Epothilones are thiazole-containing natural products with anticancer activity that are biosynthesized by polyketide synthase (PKS)-nonribosomal peptide synthetase (NRPS) enzymes EpoA–F. A cyclization domain of EpoB (Cy) assembles the thiazole functionality from an acetyl group and L-cysteine via condensation, cyclization, and dehydration. The PKS carrier protein of EpoA contributes the acetyl moiety, guided by a docking domain, whereas an NRPS EpoB carrier protein contributes L-cysteine. To visualize the structure of a cyclization domain with an accompanying docking domain, we solved a 2.03-Å resolution structure of this bidomain EpoB unit, comprising residues M1-Q497 (62 kDa) of the 160-kDa EpoB protein. We find that the N-terminal docking domain is connected to the V-shaped Cy domain by a 20-residue linker but otherwise makes no contacts to Cy. Molecular dynamic simulations and additional crystal structures reveal a high degree of flexibility for this docking domain, emphasizing the modular nature of the components of PKS-NRPS hybrid systems. These structures further reveal two 20-Å-long channels that run from distant sites on the Cy domain to the active site at the core of the enzyme, allowing two carrier proteins to dock with Cy and deliver their substrates simultaneously. Through mutagenesis and activity assays, catalytic residues N335 and D449 have been identified. Surprisingly, these residues do not map to the location of the conserved HHxxxDG motif in the structurally homologous NRPS condensation (C) domain. Thus, although both C and Cy domains have the same basic fold, their active sites appear distinct

    Structural elements of an NRPS cyclization domain and its intermodule docking domain

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    Epothilones are thiazole-containing natural products with anticancer activity that are biosynthesized by polyketide synthase (PKS)-nonribosomal peptide synthetase (NRPS) enzymes EpoA-F. A cyclization domain of EpoB (Cy) assembles the thiazole functionality from an acetyl group and l-cysteine via condensation, cyclization, and dehydration. The PKS carrier protein of EpoA contributes the acetyl moiety, guided by a docking domain, whereas an NRPS EpoB carrier protein contributes l-cysteine. To visualize the structure of a cyclization domain with an accompanying docking domain, we solved a 2.03-A resolution structure of this bidomain EpoB unit, comprising residues M1-Q497 (62 kDa) of the 160-kDa EpoB protein. We find that the N-terminal docking domain is connected to the V-shaped Cy domain by a 20-residue linker but otherwise makes no contacts to Cy. Molecular dynamic simulations and additional crystal structures reveal a high degree of flexibility for this docking domain, emphasizing the modular nature of the components of PKS-NRPS hybrid systems. These structures further reveal two 20-A-long channels that run from distant sites on the Cy domain to the active site at the core of the enzyme, allowing two carrier proteins to dock with Cy and deliver their substrates simultaneously. Through mutagenesis and activity assays, catalytic residues N335 and D449 have been identified. Surprisingly, these residues do not map to the location of the conserved HHxxxDG motif in the structurally homologous NRPS condensation (C) domain. Thus, although both C and Cy domains have the same basic fold, their active sites appear distinct

    Measurement of Oxygenated Polycyclic Aromatic Hydrocarbons Associated with a Size-Segregated Urban Aerosol

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    Size-segregated atmospheric particles were collected in Boston, MA, using a micro-orifice impactor. The samples were analyzed for oxygenated polycyclic aromatic hydrocarbons (OPAH) using gas chromatography/mass spectrometry. Seven PAH ketones (1-acenaphthenone, 9-fluorenone, 11H-benzo[a]fluoren-11-one, 7H-benzo[c]fluoren-7-one, 11H-benzo[b]fluoren-11-one, benzanthrone, and 6H-benzo[cd]pyrene-6-one), four PAH diones (1,4-naphthoquinone, phenanthrenequinone, 5,12-naphthacenequinone, and benzo[a]pyrene-6,12-dione), and one PAH dicarboxylic acid anhydride (naphthalic anhydride) were identified. Seven additional compounds with mass spectra typical of OPAH were tentatively identified. OPAH were generally distributed among aerosol size fractions based on molecular weight. Compounds with molecular weights between 168 and 208 were ap proximately evenly distributed between the fine (aerodynamic diameter, D_p, 2 μm) particles. OPAH with molecular weights of 248 and greater were associated primarily with the fine aerosol fraction. Most OPAH were distributed with particle size in a broad, unimodal hump similar to the the distributions observed for PAH in the same samples. These results suggest that OPAH are initially associated with fine particles after formation by either combustion or gas phase photooxidation and then partition to larger particles by vaporization and sorption. Two OPAH were distributed in bimodal distributions with peaks at D_p ≈ 2 μm and D_p ≈ 2 μm. These bimodal distributions may be indicative of sorption behavior different from PAH and other OPAH

    Measurement of Oxygenated Polycyclic Aromatic Hydrocarbons Associated with a Size-Segregated Urban Aerosol

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    Size-segregated atmospheric particles were collected in Boston, MA, using a micro-orifice impactor. The samples were analyzed for oxygenated polycyclic aromatic hydrocarbons (OPAH) using gas chromatography/mass spectrometry. Seven PAH ketones (1-acenaphthenone, 9-fluorenone, 11H-benzo[a]fluoren-11-one, 7H-benzo[c]fluoren-7-one, 11H-benzo[b]fluoren-11-one, benzanthrone, and 6H-benzo[cd]pyrene-6-one), four PAH diones (1,4-naphthoquinone, phenanthrenequinone, 5,12-naphthacenequinone, and benzo[a]pyrene-6,12-dione), and one PAH dicarboxylic acid anhydride (naphthalic anhydride) were identified. Seven additional compounds with mass spectra typical of OPAH were tentatively identified. OPAH were generally distributed among aerosol size fractions based on molecular weight. Compounds with molecular weights between 168 and 208 were ap proximately evenly distributed between the fine (aerodynamic diameter, D_p, 2 μm) particles. OPAH with molecular weights of 248 and greater were associated primarily with the fine aerosol fraction. Most OPAH were distributed with particle size in a broad, unimodal hump similar to the the distributions observed for PAH in the same samples. These results suggest that OPAH are initially associated with fine particles after formation by either combustion or gas phase photooxidation and then partition to larger particles by vaporization and sorption. Two OPAH were distributed in bimodal distributions with peaks at D_p ≈ 2 μm and D_p ≈ 2 μm. These bimodal distributions may be indicative of sorption behavior different from PAH and other OPAH

    Measurement of C_(24)H_(14) Polycyclic Aromatic Hydrocarbons Associated with a Size-Segregated Urban Aerosol

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    Six-ring C_(24)H_(14) (MW 302) polycyclic aromatic hydrocarbons (PAH), some of which are potent mutagens, are present in urban aerosols. Size-segregated atmospheric aerosol samples from Boston, MA, were analyzed for C_(24)H_(14) PAH by gas chromatography/mass spectrometry. Eleven peaks were found with mass to charge ratios of 302; of these, eight were identified using authentic standards. Five of the peaks were quantified. For each of these five, the distributions with respect to particle size were bimodal with the majority of the mass associated with accumulation mode particles (0.3−1.0 μm) and a smaller fraction of the mass associated with ultrafine mode particles (0.09−0.14 μm). These distribu tions are similar to those observed for PAH of molecular weight 252−278 in the same sample but different from those of benzo[ghi]perylene (MW 276) and coronene (MW 300), which were associated to a greater degree with ultrafine particles. The data suggest that C_(24)H_(14) PAH repartition to larger particles by vaporization and sorption more rapidly than do benzo[ghi]perylene and coronene. The total concentration of C_(24)H_(14) PAH (1.5 ng/m^3) was comparable to that of benzo[a]pyrene in the same sample. Because of their mutagenicities, C_(24)H_(14) PAH may make a contribution to the genotoxicity of urban aerosols comparable to that of benzo[a]pyrene

    Measurement of C_(24)H_(14) Polycyclic Aromatic Hydrocarbons Associated with a Size-Segregated Urban Aerosol

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    Six-ring C_(24)H_(14) (MW 302) polycyclic aromatic hydrocarbons (PAH), some of which are potent mutagens, are present in urban aerosols. Size-segregated atmospheric aerosol samples from Boston, MA, were analyzed for C_(24)H_(14) PAH by gas chromatography/mass spectrometry. Eleven peaks were found with mass to charge ratios of 302; of these, eight were identified using authentic standards. Five of the peaks were quantified. For each of these five, the distributions with respect to particle size were bimodal with the majority of the mass associated with accumulation mode particles (0.3−1.0 μm) and a smaller fraction of the mass associated with ultrafine mode particles (0.09−0.14 μm). These distribu tions are similar to those observed for PAH of molecular weight 252−278 in the same sample but different from those of benzo[ghi]perylene (MW 276) and coronene (MW 300), which were associated to a greater degree with ultrafine particles. The data suggest that C_(24)H_(14) PAH repartition to larger particles by vaporization and sorption more rapidly than do benzo[ghi]perylene and coronene. The total concentration of C_(24)H_(14) PAH (1.5 ng/m^3) was comparable to that of benzo[a]pyrene in the same sample. Because of their mutagenicities, C_(24)H_(14) PAH may make a contribution to the genotoxicity of urban aerosols comparable to that of benzo[a]pyrene

    Latent transforming growth factor binding protein 4 (LTBP4) is downregulated in mouse and human DCIS and mammary carcinomas

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    Transforming growth factor beta (TGF-) is able to inhibit the proliferation of epithelial cells and is involved in the carcinogenesis of mammary tumors. Three latent transforming growth factor- binding proteins (LTBPs) are known to modulate TGF- functions. The current study analyses the expression profiles of LTBP4, its isoforms LTBP1 and LTBP3, and TGF-1, TGF-2, TGF-3, and SMAD2, SMAD3 and SMAD4 in human and murine (WAP-TNP8) DCIS compared to invasive mammary tumors. Additionally mammary malignant (MCF7, Hs578T, MDA-MB361) and non malignant cell lines (Hs578BsT) were analysed. Microarray, q-PCR, immunoblot, immunohistochemistry and immunofluorescence were used. In comparison to non-malignant tissues (n = 5), LTBP4 was downregulated in all human and mouse DCIS (n = 9) and invasive mammary adenocarcinomas (n = 5) that were investigated. We also found decreased expression of bone morphogenic protein 4 (BMP4) and increased expression of its inhibitor gremlin (GREM1). Treatment of the mammary tumor cell line (Hs578T) with recombinant TGF-1 rescued BMP4 and GREM1 expression. We conclude that the lack of LTBP4-mediated targeting in malignant mammary tumor tissues may lead to a possible modification of TGF-1 and BMP bioavailability and function

    Quantitative Analysis of Histone Modifications: Formaldehyde Is a Source of Pathological N6-Formyllysine That Is Refractory to Histone Deacetylases

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    Aberrant protein modifications play an important role in the pathophysiology of many human diseases, in terms of both dysfunction of physiological modifications and the formation of pathological modifications by reaction of proteins with endogenous electrophiles. Recent studies have identified a chemical homolog of lysine acetylation, N[superscript 6]-formyllysine, as an abundant modification of histone and chromatin proteins, one possible source of which is the reaction of lysine with 3′-formylphosphate residues from DNA oxidation. Using a new liquid chromatography-coupled to tandem mass spectrometry method to quantify all N[superscript 6]-methyl-, -acetyl- and -formyl-lysine modifications, we now report that endogenous formaldehyde is a major source of N[superscript 6]-formyllysine and that this adduct is widespread among cellular proteins in all compartments. N[superscript 6]-formyllysine was evenly distributed among different classes of histone proteins from human TK6 cells at 1–4 modifications per 10[superscript 4] lysines, which contrasted strongly with lysine acetylation and mono-, di-, and tri-methylation levels of 1.5-380, 5-870, 0-1400, and 0-390 per 10[superscript 4] lysines, respectively. While isotope labeling studies revealed that lysine demethylation is not a source of N[superscript 6]-formyllysine in histones, formaldehyde exposure was observed to cause a dose-dependent increase in N[superscript 6]-formyllysine, with use of [[superscript 13]C,[superscript 2]H[subscript 2]]-formaldehyde revealing unchanged levels of adducts derived from endogenous sources. Inhibitors of class I and class II histone deacetylases did not affect the levels of N[superscript 6]-formyllysine in TK6 cells, and the class III histone deacetylase, SIRT1, had minimal activity (<10%) with a peptide substrate containing the formyl adduct. These data suggest that N[superscript 6]-formyllysine is refractory to removal by histone deacetylases, which supports the idea that this abundant protein modification could interfere with normal regulation of gene expression if it arises at conserved sites of physiological protein secondary modification
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