210 research outputs found

    Supersymmetric Electromagnetic Waves on Giants and Dual-Giants

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    We set up the BPS equations for a D3-brane moving in AdS_5 \times S^5 which preserves two supercharges and with all bosonic fields turned on in the world-volume theory. By solving these, we find generalizations of Mikhailov giants and wobbling dual-giants that include electromagnetic waves propagating on their world-volume. For these giants (dual-giants) we show that the BPS field strength is the real part of the pull-back of a holomorphic 2-form in the ambient space C^3 (C^{1,2}) onto the world-volume.Comment: 18 page

    Modifying the Sum Over Topological Sectors and Constraints on Supergravity

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    The standard lore about the sum over topological sectors in quantum field theory is that locality and cluster decomposition uniquely determine the sum over such sectors, thus leading to the usual theta-vacua. We show that without changing the local degrees of freedom, a theory can be modified such that the sum over instantons should be restricted; e.g. one should include only instanton numbers which are divisible by some integer p. This conclusion about the configuration space of quantum field theory allows us to carefully reconsider the quantization of parameters in supergravity. In particular, we show that FI-terms and nontrivial Kahler forms are quantized. This analysis also leads to a new derivation of recent results about linearized supergravity.Comment: 17 pages, minor change

    Genetic Variants Associated with Arsenic Susceptibility: Study of Purine Nucleoside Phosphorylase, Arsenic (+3) Methyltransferase, and Glutathione S-Transferase Omega Genes

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    BACKGROUND: Individual variability in arsenic metabolism may underlie individual susceptibility toward arsenic-induced skin lesions and skin cancer. Metabolism of arsenic proceeds through sequential reduction and oxidative methylation being mediated by the following genes: purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), glutathione S-transferase omega 1 (GSTO1), and omega 2 (GSTO2). PNP functions as arsenate reductase; As3MT methylates inorganic arsenic and its metabolites; and both GSTO1 and GSTO2 reduce the metabolites. Alteration in functions of these gene products may lead to arsenic-specific disease manifestations. OBJECTIVES: To find any probable association between arsenicism and the exonic single nucleotide polymorphisms (SNPs) of the above-mentioned arsenic-metabolizing genes, we screened all the exons in those genes in an arsenic-exposed population. METHODS: Using polymerase chain reaction restriction fragment length polymorphism analysis, we screened the exons in 25 cases (individuals with arsenic-induced skin lesions) and 25 controls (individuals without arsenic-induced skin lesions), both groups drinking similar arsenic-contaminated water. The exonic SNPs identified were further genotyped in a total of 428 genetically unrelated individuals (229 cases and 199 controls) for association study. RESULTS: Among four candidate genes, PNP, As3MT, GSTO1, and GSTO2, we found that distribution of three exonic polymorphisms, His20His, Gly51Ser, and Pro57Pro of PNP, was associated with arsenicism. Genotypes having the minor alleles were significantly overrepresented in the case group: odds ratio (OR) = 1.69 [95% confidence interval (CI), 1.08–2.66] for His20His; OR = 1.66 [95% CI, 1.04–2.64] for Gly51Ser; and OR = 1.67 [95% CI, 1.05–2.66] for Pro57Pro. CONCLUSIONS: The results indicate that the three PNP variants render individuals susceptible toward developing arsenic-induced skin lesions. KEY WORDS: arsenic, As3MT, GSTO1, GSTO2, PNP, skin lesion, susceptibility. Environ Health Perspect 116:501–505 (2008). doi:10.1289/ehp.10581 available via http://dx.doi.org/ [Online 14 January 2008

    Fumaric acid production from sugarcane trash hydrolysate using Rhizopus oryzae NIIST1

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    548-556Production of organic acids through fermentation of biomass feedstock is a potent strategy for co-product generation and improving economics in lignocellulose biorefinery. Sugar cane trash (SCT), a surplus available agro-residue, was exploited for the production of fumaric acid - a dicarboxylic acid with applications in the synthesis of polyester resins, as mordant and as a food additive. The isolate NIIST1 which showed the production of fumaric acid was identified as Rhizopus oryzae. Media engineering was carried out and a maximum production of fumaric acid in SCT hydrolysate incorporated media was 5.2 g/L. Response surface analyses of the interaction of parameters indicated the importance of maintaining a high C/N ratio. Results indicate the scope for developing the Rhizopus oryzae strain NIIST1 as a potent organism for fumaric acid production, since only a few microorganisms have the ability to produce industrially relevant compounds using lignocellulose biomass hydrolysates

    Fumaric acid production from sugarcane trash hydrolysate using Rhizopus oryzae NIIST 1

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    Production of organic acids through fermentation of biomass feedstock is a potent strategy for co-product generation and improving economics in lignocellulose biorefinery. Sugar cane trash (SCT), a surplus available agro-residue, was exploited for the production of fumaric acid - a dicarboxylic acid with applications in the synthesis of polyester resins, as mordant and as a food additive. The isolate NIIST 1 which showed the production of fumaric acid was identified as Rhizopus oryzae. Media engineering was carried out and a maximum production of fumaric acid in SCT hydrolysate incorporated media was 5.2 g/L. Response surface analyses of the interaction of parameters indicated the importance of maintaining a high C/N ratio. Results indicate the scope for developing the Rhizopus oryzae strain NIIST 1 as a potent organism for fumaric acid production, since only a few microorganisms have the ability to produce industrially relevant compounds using lignocellulose biomass hydrolysates

    Labeling of Multiple HIV-1 Proteins with the Biarsenical-Tetracysteine System

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    Due to its small size and versatility, the biarsenical-tetracysteine system is an attractive way to label viral proteins for live cell imaging. This study describes the genetic labeling of the human immunodeficiency virus type 1 (HIV-1) structural proteins (matrix, capsid and nucleocapsid), enzymes (protease, reverse transcriptase, RNAse H and integrase) and envelope glycoprotein 120 with a tetracysteine tag in the context of a full-length virus. We measure the impact of these modifications on the natural virus infection and, most importantly, present the first infectious HIV-1 construct containing a fluorescently-labeled nucleocapsid protein. Furthermore, due to the high background levels normally associated with the labeling of tetracysteine-tagged proteins we have also optimized a metabolic labeling system that produces infectious virus containing the natural envelope glycoproteins and specifically labeled tetracysteine-tagged proteins that can easily be detected after virus infection of T-lymphocytes. This approach can be adapted to other viral systems for the visualization of the interplay between virus and host cell during infection

    Zinc-bound metallothioneins and immune plasticity: lessons from very old mice and humans

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    The capacity of the remodelling immune responses during stress (named immune plasticity) is fundamental to reach successful ageing. We herein report two pivotal experimental models in order to demonstrate the relevance of the immune plasticity in ageing and successful ageing. These two experimental models will be compared with the capacity in remodelling the immune response in human centenarians. With regard to experimental models, one model is represented by the circadian rhythms of immune responses, the other one is the immune responses during partial hepatectomy/liver regeneration (pHx). The latter is suggestive because it mimics the immunosenescence and chronic inflammation 48 h after partial hepatectomy in the young through the continuous production of IL-6, which is the main cause of immune plasticity lack in ageing. The constant production of IL-6 leads to abnormal increments of zinc-bound Metallothionein (MT), which is in turn unable in zinc release in ageing. As a consequence, low zinc ion bioavailability appears for thymic and extrathymic immune efficiency, in particular of liver NKT cells bearing TCR γδ. The remodelling during the circadian cycle and during pHx of zinc-bound MT confers the immune plasticity of liver NKT γδ cells and NK cells in young and very old mice, not in old mice. With regard to human centenarians and their capacity in remodelling the immune response with respect to elderly, these exceptional individuals display low zinc-bound MT associated with: a) satisfactory intracellular zinc ion availability, b) more capacity in zinc release by MT, c) less inflammation due to low gene expression of IL-6 receptor (gp130), d) increased levels of IFN-gamma and number of NKT cell bearing TCR γδ. Moreover, some polymorphisms for MT tested in PBMCs from human donors are related to successful ageing. In conclusion, zinc-bound MT homeostasis is fundamental to confer the immune plasticity that is a condition "sine qua non" to achieve healthy ageing and longevity

    Genome-Wide Linkage Analysis of Global Gene Expression in Loin Muscle Tissue Identifies Candidate Genes in Pigs

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    BACKGROUND: Nearly 6,000 QTL have been reported for 588 different traits in pigs, more than in any other livestock species. However, this effort has translated into only a few confirmed causative variants. A powerful strategy for revealing candidate genes involves expression QTL (eQTL) mapping, where the mRNA abundance of a set of transcripts is used as the response variable for a QTL scan. METHODOLOGY/PRINCIPAL FINDINGS: We utilized a whole genome expression microarray and an F(2) pig resource population to conduct a global eQTL analysis in loin muscle tissue, and compared results to previously inferred phenotypic QTL (pQTL) from the same experimental cross. We found 62 unique eQTL (FDR <10%) and identified 3 gene networks enriched with genes subject to genetic control involved in lipid metabolism, DNA replication, and cell cycle regulation. We observed strong evidence of local regulation (40 out of 59 eQTL with known genomic position) and compared these eQTL to pQTL to help identify potential candidate genes. Among the interesting associations, we found aldo-keto reductase 7A2 (AKR7A2) and thioredoxin domain containing 12 (TXNDC12) eQTL that are part of a network associated with lipid metabolism and in turn overlap with pQTL regions for marbling, % intramuscular fat (% fat) and loin muscle area on Sus scrofa (SSC) chromosome 6. Additionally, we report 13 genomic regions with overlapping eQTL and pQTL involving 14 local eQTL. CONCLUSIONS/SIGNIFICANCE: Results of this analysis provide novel candidate genes for important complex pig phenotypes

    Interplay of Substrate Retention and Export Signals in Endoplasmic Reticulum Quality Control

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    BACKGROUND: Endoplasmic reticulum (ER) quality control mechanisms are part of a comprehensive system to manage cell stress. The flux of molecules is monitored to retain folding intermediates and target misfolded molecules to ER-associated degradation (ERAD) pathways. The mechanisms of sorting remain unclear. While some proteins are retained statically, the classical model substrate CPY* is found in COPII transport vesicles, suggesting a retrieval mechanism for retention. However, its management can be even more dynamic. If ERAD is saturated under stress, excess CPY* traffics to the vacuole for degradation. These observations suggest that misfolded proteins might display different signals for their management. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report the existence of a functional ER exit signal in the pro-domain of CPY*. Compromising its integrity causes ER retention through exclusion from COPII vesicles. The signal co-exists with other signals used for retention and degradation. Physiologically, the export signal is important for stress tolerance. Disabling it converts a benign protein into one that is intrinsically cytotoxic. CONCLUSIONS/SIGNIFICANCE: These data reveal the remarkable interplay between opposing signals embedded within ERAD substrate molecules and the mechanisms that decipher them. Our findings demonstrate the diversity of mechanisms deployed for protein quality control and maintenance of protein homeostasis
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