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Sample records for acetyltransferase hat hbo1

  1. Association with the origin recognition complex suggests a novel role for histone acetyltransferase Hat1p/Hat2p

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    Greenblatt Jack F

    2007-09-01

    Full Text Available Abstract Background Histone modifications have been implicated in the regulation of transcription and, more recently, in DNA replication and repair. In yeast, a major conserved histone acetyltransferase, Hat1p, preferentially acetylates lysine residues 5 and 12 on histone H4. Results Here, we report that a nuclear sub-complex consisting of Hat1p and its partner Hat2p interacts physically and functionally with the origin recognition complex (ORC. While mutational inactivation of the histone acetyltransferase (HAT gene HAT1 alone does not compromise origin firing or initiation of DNA replication, a deletion in HAT1 (or HAT2 exacerbates the growth defects of conditional orc-ts mutants. Thus, the ORC-associated Hat1p-dependent histone acetyltransferase activity suggests a novel linkage between histone modification and DNA replication. Additional genetic and biochemical evidence points to the existence of partly overlapping histone H3 acetyltransferase activities in addition to Hat1p/Hat2p for proper DNA replication efficiency. Furthermore, we demonstrated a dynamic association of Hat1p with chromatin during S-phase that suggests a role of this enzyme at the replication fork. Conclusion We have found an intriguing new association of the Hat1p-dependent histone acetyltransferase in addition to its previously known role in nuclear chromatin assembly (Hat1p/Hat2p-Hif1p. The participation of a distinct Hat1p/Hat2p sub-complex suggests a linkage of histone H4 modification with ORC-dependent DNA replication.

  2. UV Damage-Induced Phosphorylation of HBO1 Triggers CRL4DDB2-Mediated Degradation To Regulate Cell Proliferation

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    Matsunuma, Ryoichi; Ohhata, Tatsuya; Kitagawa, Kyoko; Sakai, Satoshi; Uchida, Chiharu; Shiotani, Bunsyo; Matsumoto, Masaki; Nakayama, Keiichi I.; Ogura, Hiroyuki; Shiiya, Norihiko; Kitagawa, Masatoshi

    2015-01-01

    Histone acetyltransferase binding to ORC-1 (HBO1) is a critically important histone acetyltransferase for forming the prereplicative complex (pre-RC) at the replication origin. Pre-RC formation is completed by loading of the MCM2-7 heterohexameric complex, which functions as a helicase in DNA replication. HBO1 recruited to the replication origin by CDT1 acetylates histone H4 to relax the chromatin conformation and facilitates loading of the MCM complex onto replication origins. However, the acetylation status and mechanism of regulation of histone H3 at replication origins remain elusive. HBO1 positively regulates cell proliferation under normal cell growth conditions. Whether HBO1 regulates proliferation in response to DNA damage is poorly understood. In this study, we demonstrated that HBO1 was degraded after DNA damage to suppress cell proliferation. Ser50 and Ser53 of HBO1 were phosphorylated in an ATM/ATR DNA damage sensor-dependent manner after UV treatment. ATM/ATR-dependently phosphorylated HBO1 preferentially interacted with DDB2 and was ubiquitylated by CRL4DDB2. Replacement of endogenous HBO1 in Ser50/53Ala mutants maintained acetylation of histone H3K14 and impaired cell cycle regulation in response to UV irradiation. Our findings demonstrate that HBO1 is one of the targets in the DNA damage checkpoint. These results show that ubiquitin-dependent control of the HBO1 protein contributes to cell survival during UV irradiation. PMID:26572825

  3. Expression profiling of S. pombe acetyltransferase mutants identifies redundant pathways of gene regulation

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    Wright Anthony PH

    2010-01-01

    Full Text Available Abstract Background Histone acetyltransferase enzymes (HATs are implicated in regulation of transcription. HATs from different families may overlap in target and substrate specificity. Results We isolated the elp3+ gene encoding the histone acetyltransferase subunit of the Elongator complex in fission yeast and characterized the phenotype of an Δelp3 mutant. We examined genetic interactions between Δelp3 and two other HAT mutants, Δmst2 and Δgcn5 and used whole genome microarray analysis to analyze their effects on gene expression. Conclusions Comparison of phenotypes and expression profiles in single, double and triple mutants indicate that these HAT enzymes have overlapping functions. Consistent with this, overlapping specificity in histone H3 acetylation is observed. However, there is no evidence for overlap with another HAT enzyme, encoded by the essential mst1+ gene.

  4. Histone acetyltransferases : challenges in targeting bi-substrate enzymes

    NARCIS (Netherlands)

    Wapenaar, Hannah; Dekker, Frank J

    2016-01-01

    Histone acetyltransferases (HATs) are epigenetic enzymes that install acetyl groups onto lysine residues of cellular proteins such as histones, transcription factors, nuclear receptors, and enzymes. HATs have been shown to play a role in diseases ranging from cancer and inflammatory diseases to

  5. Valproic acid exposure decreases Cbp/p300 protein expression and histone acetyltransferase activity in P19 cells

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    Lamparter, Christina L. [Department of Biomedical and Molecular Sciences, Graduate Program in Pharmacology and Toxicology, Queen' s University, Kingston, Ontario K7L 3N6 (Canada); Winn, Louise M., E-mail: winnl@queensu.ca [Department of Biomedical and Molecular Sciences, Graduate Program in Pharmacology and Toxicology, Queen' s University, Kingston, Ontario K7L 3N6 (Canada); School of Environmental Studies, Queen' s University, Kingston, Ontario K7L 3N6 (Canada)

    2016-09-01

    The teratogenicity of the antiepileptic drug valproic acid (VPA) is well established and its inhibition of histone deacetylases (HDAC) is proposed as an initiating factor. Recently, VPA-mediated HDAC inhibition was demonstrated to involve transcriptional downregulation of histone acetyltransferases (HATs), which was proposed to compensate for the increased acetylation resulting from HDAC inhibition. Cbp and p300 are HATs required for embryonic development and deficiencies in either are associated with congenital malformations and embryolethality. The objective of the present study was to characterize Cbp/p300 following VPA exposure in P19 cells. Consistent with previous studies, exposure to 5 mM VPA over 24 h induced a moderate decrease in Cbp/p300 mRNA, which preceded a strong decrease in total cellular protein mediated by ubiquitin-proteasome degradation. Nuclear Cbp/p300 protein was also decreased following VPA exposure, although to a lesser extent. Total cellular and nuclear p300 HAT activity was reduced proportionately to p300 protein levels, however while total cellular HAT activity also decreased, nuclear HAT activity was unaffected. Using the Cbp/p300 HAT inhibitor C646, we demonstrated that HAT inhibition similarly affected many of the same endpoints as VPA, including increased reactive oxygen species and caspase-3 cleavage, the latter of which could be attenuated by pre-treatment with the antioxidant catalase. C646 exposure also decreased NF-κB/p65 protein, which was not due to reduced mRNA and was not attenuated with catalase pre-treatment. This study provides support for an adaptive HAT response following VPA exposure and suggests that reduced Cbp/p300 HAT activity could contribute to VPA-mediated alterations. - Highlights: • VPA exposure in vitro downregulates Cbp/p300 mRNA and induces protein degradation. • Cbp/p300 histone acetyltransferase activity is similarly reduced with VPA exposure. • Inhibition of Cbp/p300 acetyltransferase activity

  6. H4 replication-dependent diacetylation and Hat1 promote S-phase chromatin assembly in vivo

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    Ejlassi-Lassallette, Aïda; Mocquard, Eloïse; Arnaud, Marie-Claire; Thiriet, Christophe

    2011-01-01

    While specific posttranslational modification patterns within the H3 and H4 tail domains are associated with the S-phase, their actual functions in replication-dependent chromatin assembly have not yet been defined. Here we used incorporation of trace amounts of recombinant proteins into naturally synchronous macroplasmodia of Physarum polycephalum to examine the function of H3 and H4 tail domains in replication-coupled chromatin assembly. We found that the H3/H4 complex lacking the H4 tail domain was not efficiently recovered in nuclei, whereas depletion of the H3 tail domain did not impede nuclear import but chromatin assembly failed. Furthermore, our results revealed that the proper pattern of acetylation on the H4 tail domain is required for nuclear import and chromatin assembly. This is most likely due to binding of Hat1, as coimmunoprecipitation experiments showed Hat1 associated with predeposition histones in the cytoplasm and with replicating chromatin. These results suggest that the type B histone acetyltransferase assists in shuttling the H3/H4 complex from cytoplasm to the replication forks. PMID:21118997

  7. Small molecule inhibitors of histone deacetylases and acetyltransferases as potential therapeutics in oncology

    NARCIS (Netherlands)

    van den Bosch, Thea; Leus, Niek; Timmerman, Tirza; Dekker, Frank J

    2016-01-01

    Uncontrolled cell proliferation and resistance to apoptosis in cancer are, among others, regulated by post-translational modifications of histone proteins. The most investigated type of histone modification is lysine acetylation. Histone acetyltransferases (HATs), acetylate histone lysine residues,

  8. Histone acetyltransferase (HAT) activity of p300 modulates human T lymphotropic virus type 1 p30II-mediated repression of LTR transcriptional activity

    International Nuclear Information System (INIS)

    Michael, Bindhu; Nair, Amrithraj M.; Datta, Antara; Hiraragi, Hajime; Ratner, Lee; Lairmore, Michael D.

    2006-01-01

    Human T-lymphotropic virus type-1 (HTLV-1) is a deltaretrovirus that causes adult T cell leukemia/lymphoma, and is implicated in a variety of lymphocyte-mediated inflammatory disorders. HTLV-1 provirus has regulatory and accessory genes in four pX open reading frames. HTLV-1 pX ORF-II encodes two proteins, p13 II and p30 II , which are incompletely defined in virus replication or pathogenesis. We have demonstrated that pX ORF-II mutations block virus replication in vivo and that ORF-II encoded p30 II , a nuclear-localizing protein that binds with CREB-binding protein (CBP)/p300, represses CREB and Tax responsive element (TRE)-mediated transcription. Herein, we have identified p30 II motifs important for p300 binding and in regulating TRE-mediated transcription in the absence and presence of HTLV-1 provirus. Within amino acids 100-179 of p30 II , a region important for repression of LTR-mediated transcription, we identified a single lysine residue at amino acid 106 (K3) that significantly modulates the ability of p30 II to repress TRE-mediated transcription. Exogenous p300, in a dose-responsive manner, reverses p30 II -dependent repression of TRE-mediated transcription, in the absence or presence of the provirus, In contrast to wild type p300, p300 HAT mutants (defective in histone acetyltransferase activity) only partially rescued p30 II -mediated LTR repression. Deacetylation by histone deacetylase-1 (HDAC-1) enhanced p30 II -mediated LTR repression, while inhibition of deacetylation by trichostatin A decreases p30 II -mediated LTR repression. Collectively, our data indicate that HTLV-1 p30 II modulates viral gene expression in a cooperative manner with p300-mediated acetylation

  9. Ervaringen met ICT-onderzoek in het HBO.

    NARCIS (Netherlands)

    van Leeuwen, H.; Teeuw, W.J.; Tangelder, R.; Griffioen, P.; Krose, B.; Schouten, B.

    2011-01-01

    In dit artikel wordt het belang aangegeven van onderzoeksvaardigheden in het HBO. Met de komst van de lectoraten en de nieuwe positionering van het HBO is het belangrijk om een antwoord te vinden hoe het onderzoek binnen het HBO vormgegeven moet worden. Hierbij wordt gekeken naar de bruikbaarheid

  10. Hvad er fantastisk ved HBO-serien Game of Thrones?

    DEFF Research Database (Denmark)

    Schubart, Rikke

    2013-01-01

    Blogindlæg på videnskab.dk, kaldt "Hvad er fantastisk ved HBO-serien Game of Thrones?" om HBO tv-serien Game of Thrones......Blogindlæg på videnskab.dk, kaldt "Hvad er fantastisk ved HBO-serien Game of Thrones?" om HBO tv-serien Game of Thrones...

  11. Three-dimensional structure of a Streptomyces sviceus GNAT acetyltransferase with similarity to the C-terminal domain of the human GH84 O-GlcNAcase

    International Nuclear Information System (INIS)

    He, Yuan; Roth, Christian; Turkenburg, Johan P.; Davies, Gideon J.

    2013-01-01

    The crystal structure of a bacterial acetyltransferase with 27% sequence identity to the C-terminal domain of human O-GlcNAcase has been solved at 1.5 Å resolution. This S. sviceus protein is compared with known GCN5-related acetyltransferases, adding to the diversity observed in this superfamily. The mammalian O-GlcNAc hydrolysing enzyme O-GlcNAcase (OGA) is a multi-domain protein with glycoside hydrolase activity in the N-terminus and with a C-terminal domain that has low sequence similarity to known acetyltransferases, prompting speculation, albeit controversial, that the C-terminal domain may function as a histone acetyltransferase (HAT). There are currently scarce data available regarding the structure and function of this C-terminal region. Here, a bacterial homologue of the human OGA C-terminal domain, an acetyltransferase protein (accession No. ZP-05014886) from Streptomyces sviceus (SsAT), was cloned and its crystal structure was solved to high resolution. The structure reveals a conserved protein core that has considerable structural homology to the acetyl-CoA (AcCoA) binding site of GCN5-related acetyltransferases (GNATs). Calorimetric data further confirm that SsAT is indeed able to bind AcCoA in solution with micromolar affinity. Detailed structural analysis provided insight into the binding of AcCoA. An acceptor-binding cavity was identified, indicating that the physiological substrate of SsAT may be a small molecule. Consistent with recently published work, the SsAT structure further questions a HAT function for the human OGA domain

  12. Three-dimensional structure of a Streptomyces sviceus GNAT acetyltransferase with similarity to the C-terminal domain of the human GH84 O-GlcNAcase

    Energy Technology Data Exchange (ETDEWEB)

    He, Yuan [Northwest University, Xi’an 710069 (China); The University of York, York YO10 5DD (United Kingdom); Roth, Christian; Turkenburg, Johan P.; Davies, Gideon J., E-mail: gideon.davies@york.ac.uk [The University of York, York YO10 5DD (United Kingdom); Northwest University, Xi’an 710069 (China)

    2014-01-01

    The crystal structure of a bacterial acetyltransferase with 27% sequence identity to the C-terminal domain of human O-GlcNAcase has been solved at 1.5 Å resolution. This S. sviceus protein is compared with known GCN5-related acetyltransferases, adding to the diversity observed in this superfamily. The mammalian O-GlcNAc hydrolysing enzyme O-GlcNAcase (OGA) is a multi-domain protein with glycoside hydrolase activity in the N-terminus and with a C-terminal domain that has low sequence similarity to known acetyltransferases, prompting speculation, albeit controversial, that the C-terminal domain may function as a histone acetyltransferase (HAT). There are currently scarce data available regarding the structure and function of this C-terminal region. Here, a bacterial homologue of the human OGA C-terminal domain, an acetyltransferase protein (accession No. ZP-05014886) from Streptomyces sviceus (SsAT), was cloned and its crystal structure was solved to high resolution. The structure reveals a conserved protein core that has considerable structural homology to the acetyl-CoA (AcCoA) binding site of GCN5-related acetyltransferases (GNATs). Calorimetric data further confirm that SsAT is indeed able to bind AcCoA in solution with micromolar affinity. Detailed structural analysis provided insight into the binding of AcCoA. An acceptor-binding cavity was identified, indicating that the physiological substrate of SsAT may be a small molecule. Consistent with recently published work, the SsAT structure further questions a HAT function for the human OGA domain.

  13. Curcumin and its demethoxy derivatives possess p300 HAT inhibitory activity and suppress hypertrophic responses in cardiomyocytes

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    Yoichi Sunagawa

    2018-04-01

    Full Text Available The natural compound, curcumin (CUR, possesses several pharmacological properties, including p300-specific histone acetyltransferase (HAT inhibitory activity. In our previous study, we demonstrated that CUR could prevent the development of cardiac hypertrophy by inhibiting p300-HAT activity. Other major curcuminoids isolated from Curcuma longa including demethoxycurcumin (DMC and bisdemethoxycurcumin (BDMC are structural analogs of CUR. In present study, we first confirmed the effect of these three curcuminoid analogs on p300-HAT activity and cardiomyocyte hypertrophy.Our results showed that DMC and BDMC inhibited p300-HAT activity and cardiomyocyte hypertrophy to almost the same extent as CUR. As the three compounds have structural differences in methoxy groups at the 3-position of their phenol rings, our results suggest that these methoxy groups are not involved in the inhibitory effects on p300-HAT activity and cardiac hypertrophy. These findings provide useful insights into the structure–activity relationship and biological activity of curcuminoids for p300-HAT activity and cardiomyocyte hypertrophy. Keywords: Curcumin, Demethoxycurcumin, Bisdemethoxycurcumin, p300, Cardiomyocyte hypertrophy

  14. The lysine acetyltransferase activator Brpf1 governs dentate gyrus development through neural stem cells and progenitors.

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    Linya You

    2015-03-01

    Full Text Available Lysine acetylation has recently emerged as an important post-translational modification in diverse organisms, but relatively little is known about its roles in mammalian development and stem cells. Bromodomain- and PHD finger-containing protein 1 (BRPF1 is a multidomain histone binder and a master activator of three lysine acetyltransferases, MOZ, MORF and HBO1, which are also known as KAT6A, KAT6B and KAT7, respectively. While the MOZ and MORF genes are rearranged in leukemia, the MORF gene is also mutated in prostate and other cancers and in four genetic disorders with intellectual disability. Here we show that forebrain-specific inactivation of the mouse Brpf1 gene causes hypoplasia in the dentate gyrus, including underdevelopment of the suprapyramidal blade and complete loss of the infrapyramidal blade. We trace the developmental origin to compromised Sox2+ neural stem cells and Tbr2+ intermediate neuronal progenitors. We further demonstrate that Brpf1 loss deregulates neuronal migration, cell cycle progression and transcriptional control, thereby causing abnormal morphogenesis of the hippocampus. These results link histone binding and acetylation control to hippocampus development and identify an important epigenetic regulator for patterning the dentate gyrus, a brain structure critical for learning, memory and adult neurogenesis.

  15. Tip off the HAT- Epigenetic control of learning and memory by Drosophila Tip60.

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    Xu, Songjun; Elefant, Felice

    2015-01-01

    Disruption of epigenetic gene control mechanisms involving histone acetylation in the brain causes cognitive impairment, a debilitating hallmark of most neurodegenerative disorders. Histone acetylation regulates cognitive gene expression via chromatin packaging control in neurons. Unfortunately, the histone acetyltransferases (HATs) that generate such neural epigenetic signatures and their mechanisms of action remain unclear. Our recent findings provide insight into this question by demonstrating that Tip60 HAT action is critical for morphology and function of the mushroom body (MB), the learning and memory center in the Drosophila brain. We show that Tip60 is robustly produced in MB Kenyon cells and extending axonal lobes and that targeted MB Tip60 HAT loss results in axonal outgrowth disruption. Functional consequences of loss and gain of Tip60 HAT levels in the MB are evidenced by defects in memory. Tip60 ChIP-Seq analysis reveals enrichment for genes that function in cognitive processes and accordingly, key genes representing these pathways are misregulated in the Tip60 HAT mutant fly brain. Remarkably, increasing levels of Tip60 in the MB rescues learning and memory deficits resulting from Alzheimer's disease associated amyloid precursor protein (APP) induced neurodegeneration. Our studies highlight the potential of HAT activators as a therapeutic option for cognitive disorders.

  16. Subunits of ADA-two-A-containing (ATAC) or Spt-Ada-Gcn5-acetyltrasferase (SAGA) Coactivator Complexes Enhance the Acetyltransferase Activity of GCN5.

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    Riss, Anne; Scheer, Elisabeth; Joint, Mathilde; Trowitzsch, Simon; Berger, Imre; Tora, László

    2015-11-27

    Histone acetyl transferases (HATs) play a crucial role in eukaryotes by regulating chromatin architecture and locus specific transcription. GCN5 (KAT2A) is a member of the GNAT (Gcn5-related N-acetyltransferase) family of HATs. In metazoans this enzyme is found in two functionally distinct coactivator complexes, SAGA (Spt Ada Gcn5 acetyltransferase) and ATAC (Ada Two A-containing). These two multiprotein complexes comprise complex-specific and shared subunits, which are organized in functional modules. The HAT module of ATAC is composed of GCN5, ADA2a, ADA3, and SGF29, whereas in the SAGA HAT module ADA2b is present instead of ADA2a. To better understand how the activity of human (h) hGCN5 is regulated in the two related, but different, HAT complexes we carried out in vitro HAT assays. We compared the activity of hGCN5 alone with its activity when it was part of purified recombinant hATAC or hSAGA HAT modules or endogenous hATAC or hSAGA complexes using histone tail peptides and full-length histones as substrates. We demonstrated that the subunit environment of the HAT complexes into which GCN5 incorporates determines the enhancement of GCN5 activity. On histone peptides we show that all the tested GCN5-containing complexes acetylate mainly histone H3K14. Our results suggest a stronger influence of ADA2b as compared with ADA2a on the activity of GCN5. However, the lysine acetylation specificity of GCN5 on histone tails or full-length histones was not changed when incorporated in the HAT modules of ATAC or SAGA complexes. Our results thus demonstrate that the catalytic activity of GCN5 is stimulated by subunits of the ADA2a- or ADA2b-containing HAT modules and is further increased by incorporation of the distinct HAT modules in the ATAC or SAGA holo-complexes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Inhibition of PCAF Histone Acetyltransferase, Cytotoxicity and Cell Permeability of 2-Acylamino-1-(3- or 4-Carboxy-phenylbenzamides

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    Eunsook Ma

    2012-11-01

    Full Text Available Small molecule HAT inhibitors are useful tools to unravel the role of histone acetyltransferases (HATs in the cell and they also have relevance in oncology. We synthesized a series of 2-acylamino-1-(3- or 4-carboxyphenylbenzamides 8–19 bearing C6, C8, C10, C12, C14, and C16 acyl chains at the 2-amino position of 2-aminobenzoic acid. Enzyme inhibition of these compounds was investigated using in vitro PCAF HAT assays. The inhibitory activities of compounds 8–10, 16, and 19 were similar to that of anacardic acid, and 17 was found to be more active than anacardic acid at 100 μM. Compounds 11–15 showed the low inhibitory activity on PCAF HAT. The cytotoxicity of the synthesized compounds was evaluated by SRB (sulforhodamine B assay against seven human cancer cell lines: HT-29 (colon, HCT-116 (colon, MDA-231 (breast, A549 (lung, Hep3B (hepatoma, HeLa (cervical and Caki (kidney and one normal cell line (HSF. Compound 17 was more active than anacardic acid against human colon cancer (HCT 116, IC50: 29.17 μM, human lung cancer (A549, IC50: 32.09 μM cell lines. 18 was more active than anacardic acid against human colon cancer (HT-29, IC50: 35.49 μM and HCT 116, IC50: 27.56 μM, human lung cancer (A549, IC50: 30.69 μM, and human cervical cancer (HeLa, IC50: 34.41 μM cell lines. The apparent permeability coefficient (Papp, cm/s values of two compounds (16 and 17 were evaluated as 68.21 and 71.48 × 10−6 cm/s by Caco-2 cell permeability assay.

  18. Interactions of Histone Acetyltransferase p300 with the Nuclear Proteins Histone and HMGB1, As Revealed by Single Molecule Atomic Force Spectroscopy.

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    Banerjee, S; Rakshit, T; Sett, S; Mukhopadhyay, R

    2015-10-22

    One of the important properties of the transcriptional coactivator p300 is histone acetyltransferase (HAT) activity that enables p300 to influence chromatin action via histone modulation. p300 can exert its HAT action upon the other nuclear proteins too--one notable example being the transcription-factor-like protein HMGB1, which functions also as a cytokine, and whose accumulation in the cytoplasm, as a response to tissue damage, is triggered by its acetylation. Hitherto, no information on the structure and stability of the complexes between full-length p300 (p300FL) (300 kDa) and the histone/HMGB1 proteins are available, probably due to the presence of unstructured regions within p300FL that makes it difficult to be crystallized. Herein, we have adopted the high-resolution atomic force microscopy (AFM) approach, which allows molecularly resolved three-dimensional contour mapping of a protein molecule of any size and structure. From the off-rate and activation barrier values, obtained using single molecule dynamic force spectroscopy, the biochemical proposition of preferential binding of p300FL to histone H3, compared to the octameric histone, can be validated. Importantly, from the energy landscape of the dissociation events, a model for the p300-histone and the p300-HMGB1 dynamic complexes that HAT forms, can be proposed. The lower unbinding forces of the complexes observed in acetylating conditions, compared to those observed in non-acetylating conditions, indicate that upon acetylation, p300 tends to weakly associate, probably as an outcome of charge alterations on the histone/HMGB1 surface and/or acetylation-induced conformational changes. To our knowledge, for the first time, a single molecule level treatment of the interactions of HAT, where the full-length protein is considered, is being reported.

  19. Inhibition of PCAF histone acetyltransferase, cytotoxicity and cell permeability of 2-acylamino-1-(3- or 4-carboxy-phenyl)benzamides.

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    Park, Woong Jae; Ma, Eunsook

    2012-11-05

    Small molecule HAT inhibitors are useful tools to unravel the role of histone acetyltransferases (HATs) in the cell and they also have relevance in oncology. We synthesized a series of 2-acylamino-1-(3- or 4-carboxyphenyl)benzamides 8–19 bearing C6, C8, C10, C12, C14, and C16 acyl chains at the 2-amino position of 2-aminobenzoic acid. Enzyme inhibition of these compounds was investigated using in vitro PCAF HAT assays. The inhibitory activities of compounds 8–10, 16, and 19 were similar to that of anacardic acid, and 17 was found to be more active than anacardic acid at 100 μM. Compounds 11–15 showed the low inhibitory activity on PCAF HAT. The cytotoxicity of the synthesized compounds was evaluated by SRB (sulforhodamine B) assay against seven human cancer cell lines: HT-29 (colon), HCT-116 (colon), MDA-231 (breast), A549 (lung), Hep3B (hepatoma), HeLa (cervical) and Caki (kidney) and one normal cell line (HSF). Compound 17 was more active than anacardic acid against human colon cancer (HCT 116, IC(50): 29.17 μM), human lung cancer (A549, IC₅₀: 32.09 μM) cell lines. 18 was more active than anacardic acid against human colon cancer (HT-29, IC₅₀: 35.49 μM and HCT 116, IC₅₀: 27.56 μM), human lung cancer (A549, IC₅₀: 30.69 μM), and human cervical cancer (HeLa, IC₅₀: 34.41 μM) cell lines. The apparent permeability coefficient (P(app), cm/s) values of two compounds (16 and 17) were evaluated as 68.21 and 71.48 × 10⁻⁶ cm/s by Caco-2 cell permeability assay.

  20. Epigenetic control of learning and memory in Drosophila by Tip60 HAT action.

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    Xu, Songjun; Wilf, Rona; Menon, Trisha; Panikker, Priyalakshmi; Sarthi, Jessica; Elefant, Felice

    2014-12-01

    Disruption of epigenetic gene control mechanisms in the brain causes significant cognitive impairment that is a debilitating hallmark of most neurodegenerative disorders, including Alzheimer's disease (AD). Histone acetylation is one of the best characterized of these epigenetic mechanisms that is critical for regulating learning- and memory- associated gene expression profiles, yet the specific histone acetyltransferases (HATs) that mediate these effects have yet to be fully characterized. Here, we investigate an epigenetic role for the HAT Tip60 in learning and memory formation using the Drosophila CNS mushroom body (MB) as a well-characterized cognition model. We show that Tip60 is endogenously expressed in the Kenyon cells, the intrinsic neurons of the MB, and in the MB axonal lobes. Targeted loss of Tip60 HAT activity in the MB causes thinner and shorter axonal lobes while increasing Tip60 HAT levels cause no morphological defects. Functional consequences of both loss and gain of Tip60 HAT levels in the MB are evidenced by defects in immediate-recall memory. Our ChIP-Seq analysis reveals that Tip60 target genes are enriched for functions in cognitive processes, and, accordingly, key genes representing these pathways are misregulated in the Tip60 HAT mutant fly brain. Remarkably, we find that both learning and immediate-recall memory deficits that occur under AD-associated, amyloid precursor protein (APP)-induced neurodegenerative conditions can be effectively rescued by increasing Tip60 HAT levels specifically in the MB. Together, our findings uncover an epigenetic transcriptional regulatory role for Tip60 in cognitive function and highlight the potential of HAT activators as a therapeutic option for neurodegenerative disorders. Copyright © 2014 by the Genetics Society of America.

  1. BRPF3-HBO1 regulates replication origin activation and histone H3K14 acetylation

    DEFF Research Database (Denmark)

    Feng, Yunpeng; Vlassis, Arsenios; Roques, Céline

    2016-01-01

    implicated in replication control by measuring RPA accumulation upon replication stress. We identify six factors required for normal rates of DNA replication and characterize a function of the bromodomain and PHD finger-containing protein 3 (BRPF3) in replication initiation. BRPF3 forms a complex with HBO1...

  2. Management of postoperative radiation injury of the urinary bladder by hyperbaric oxygen (HBO)

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    Peusch-Dreyer, D.; Dreyer, K.H. [Zentrum fuer Tauch- und Ueberdruckmedizin (ZETUeM), Bremen (Germany); Mueller, C.D. [Druckkammerzentrum Magdeburg (Germany); Carl, U. [Klinik fuer Strahlentherapie und Radioonkologie, Universitaet Duesseldorf (Germany)

    1998-11-01

    Aim: In many case reports the success of treatment of late complications of radiotherapy with hyperbaric oxygenation (HBO) has been shown. This synopsis attempts to review HBO in the treatment of chronic radiation injury of the bladder. Patients and methods: Three female patients who had developed urge-incontinence after a Wertheim operation and combined brachy-teletherapy with cobalt-60 and afterloading and did not respond to various drug therapies, were treated with HBO to a maximum of 40 applications. Results: In all patients HBO haltered and inverted the dynamic process underlying chronic bladder changes after irradiation. Rationales for the HBO are the reduction of tissue hypoxia and the induction of neoangiogenesis. Conclusions: There are no prospective trials up to date showing the benefit of HBO to urinary disorders caused by radiation cystitis. The positive results of our retrospective study should encourage clinicians to initiate prospective studies with the use of HBO in the treatment of radiation cystitis. (orig.) [Deutsch] Ziel: Ueber die erfolgreiche Anwendung der hyperbaren Sauerstofftherapie (HBO) zur Behandlung von Strahlenspaetkomplikationen ist in zahlreichen Publikationen berichtet worden. Ziel dieser Arbeit ist es, den Einsatz der HBO bei der Behandlung von Miktionsbeschwerden bei chronisch radiogenen Harnblasenschaeden zu bewerten. Patienten und Methode: Drei Patientinnen, die nach einer kombinierten Brachyteletherapie mit Kobalt 60 und Afterloading nach Wertheim-Operation unter einer medikamentoes nicht zu beeinflussenden Urge-Inkontinenz litten, wurden der HBO mit maximal 40 Behandlungen zugefuehrt. Ergebnisse: Die HBO war bei allen Patientinnen in der Lage, den dynamischen Krankheitsprozess der Strahlenzystitis aufzuhalten und teilweise umzukehren. Grundlage hierfuer ist die Beseitigung der Gewebshypoxie. Dieses wiederum stellt die Voraussetzung fuer eine Neovaskularisation im bestrahlten Gewebe dar. Schlussfolgerung: Prospektive Studien

  3. Delphinidin, a specific inhibitor of histone acetyltransferase, suppresses inflammatory signaling via prevention of NF-κB acetylation in fibroblast-like synoviocyte MH7A cells

    International Nuclear Information System (INIS)

    Seong, Ah-Reum; Yoo, Jung-Yoon; Choi, KyungChul; Lee, Mee-Hee; Lee, Yoo-Hyun; Lee, Jeongmin; Jun, Woojin; Kim, Sunoh; Yoon, Ho-Geun

    2011-01-01

    Highlights: → Delphinidin is a novel inhibitor of p300/CBP histone acetyltransferase. → Delphinidin prevents the hyperacetylation of p65 by inhibiting the HAT activity of p300/CBP. → Delphinidin efficiently suppresses the expression of inflammatory cytokines in MH7A cells via hypoacetylation of NF-κB. → Delphinidin inhibits cytokine release in the Jurkat T lymphocyte cell line. -- Abstract: Histone acetyltransferase (HAT) inhibitors (HATi) isolated from dietary compounds have been shown to suppress inflammatory signaling, which contributes to rheumatoid arthritis. Here, we identified a novel HATi in Punica granatum L. known as delphinidin (DP). DP did not affect the activity of other epigenetic enzymes (histone deacetylase, histone methyltransferase, or sirtuin1). DP specifically inhibited the HAT activities of p300/CBP. It also inhibited p65 acetylation in MH7A cells, a human rheumatoid arthritis synovial cell line. DP-induced hypoacetylation was accompanied by cytosolic accumulation of p65 and nuclear localization of IKBα. Accordingly, DP treatment inhibited TNFα-stimulated increases in NF-κB function and expression of NF-κB target genes in these cells. Importantly, DP suppressed lipopolysaccharide-induced pro-inflammatory cytokine expression in Jurkat T lymphocytes, demonstrating that HATi efficiently suppresses cytokine-mediated immune responses. Together, these results show that the HATi activity of DP counters anti-inflammatory signaling by blocking p65 acetylation and that this compound may be useful in preventing inflammatory arthritis.

  4. Delphinidin, a specific inhibitor of histone acetyltransferase, suppresses inflammatory signaling via prevention of NF-{kappa}B acetylation in fibroblast-like synoviocyte MH7A cells

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Ah-Reum; Yoo, Jung-Yoon; Choi, KyungChul [Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, College of Medicine, Yonsei University, Seoul (Korea, Republic of); Lee, Mee-Hee [Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, College of Medicine, Yonsei University, Seoul (Korea, Republic of); Brain Korea 21 Project for Medical Sciences, Yonsei University, College of Medicine, Seoul (Korea, Republic of); Lee, Yoo-Hyun [Department of Food Science and Nutrition, The University of Suwon, Kyunggi-do (Korea, Republic of); Lee, Jeongmin [Department of Medical Nutrition, Kyung Hee University, Kyunggi-do (Korea, Republic of); Jun, Woojin [Department of Food and Nutrition, Chonnam National University, Gwangju (Korea, Republic of); Kim, Sunoh, E-mail: sunoh@korea.ac.kr [Jeollanamdo Institute of Natural Resources Research, Jeonnam (Korea, Republic of); Yoon, Ho-Geun, E-mail: yhgeun@yuhs.ac [Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, College of Medicine, Yonsei University, Seoul (Korea, Republic of); Brain Korea 21 Project for Medical Sciences, Yonsei University, College of Medicine, Seoul (Korea, Republic of)

    2011-07-08

    Highlights: {yields} Delphinidin is a novel inhibitor of p300/CBP histone acetyltransferase. {yields} Delphinidin prevents the hyperacetylation of p65 by inhibiting the HAT activity of p300/CBP. {yields} Delphinidin efficiently suppresses the expression of inflammatory cytokines in MH7A cells via hypoacetylation of NF-{kappa}B. {yields} Delphinidin inhibits cytokine release in the Jurkat T lymphocyte cell line. -- Abstract: Histone acetyltransferase (HAT) inhibitors (HATi) isolated from dietary compounds have been shown to suppress inflammatory signaling, which contributes to rheumatoid arthritis. Here, we identified a novel HATi in Punica granatum L. known as delphinidin (DP). DP did not affect the activity of other epigenetic enzymes (histone deacetylase, histone methyltransferase, or sirtuin1). DP specifically inhibited the HAT activities of p300/CBP. It also inhibited p65 acetylation in MH7A cells, a human rheumatoid arthritis synovial cell line. DP-induced hypoacetylation was accompanied by cytosolic accumulation of p65 and nuclear localization of IKB{alpha}. Accordingly, DP treatment inhibited TNF{alpha}-stimulated increases in NF-{kappa}B function and expression of NF-{kappa}B target genes in these cells. Importantly, DP suppressed lipopolysaccharide-induced pro-inflammatory cytokine expression in Jurkat T lymphocytes, demonstrating that HATi efficiently suppresses cytokine-mediated immune responses. Together, these results show that the HATi activity of DP counters anti-inflammatory signaling by blocking p65 acetylation and that this compound may be useful in preventing inflammatory arthritis.

  5. Targeting Specific HATs for Neurodegenerative Disease Treatment: Translating Basic Biology to Therapeutic Possibilities

    Directory of Open Access Journals (Sweden)

    Sheila K. Pirooznia

    2013-03-01

    Full Text Available Dynamic epigenetic regulation of neurons is emerging as a fundamental mechanism by which neurons adapt their transcriptional responses to specific developmental and environmental cues. While defects within the neural epigenome have traditionally been studied in the context of early developmental and heritable cognitive disorders, recent studies point to aberrant histone acetylation status as a key mechanism underlying acquired inappropriate alterations of genome structure and function in post-mitotic neurons during the aging process. Indeed, it is becoming increasingly evident that chromatin acetylation status can be impaired during the lifetime of neurons through mechanisms related to loss of function of histone acetyltransferase (HATs activity. Several HATs have been shown to participate in vital neuronal functions such as regulation of neuronal plasticity and memory formation. As such, dysregulation of such HATs has been implicated in the pathogenesis associated with age-associated neurodegenerative diseases and cognitive decline. In order to counteract the loss of HAT function in neurodegenerative diseases, the current therapeutic strategies involve the use of small molecules called histone deacetylase (HDAC inhibitors that antagonize HDAC activity and thus enhance acetylation levels. Although this strategy has displayed promising therapeutic effects, currently used HDAC inhibitors lack target specificity, raising concerns about their applicability. With rapidly evolving literature on HATs and their respective functions in mediating neuronal survival and higher order brain function such as learning and memory, modulating the function of specific HATs holds new promises as a therapeutic tool in neurodegenerative diseases. In this review, we focus on the recent progress in research regarding epigenetic histone acetylation mechanisms underlying neuronal activity and cognitive function. We discuss the current understanding of specific HDACs and

  6. BBC ja HBO taaselustasid Rooma viletsuse ja hiilguse / Brigitta Davidjants

    Index Scriptorium Estoniae

    Davidjants, Brigitta, 1983-

    2005-01-01

    12-osaline ajalooline kostüümidraama - seriaali Rooma impeeriumi ajast "Rooma" tootsid Ameerika tootja Home Box Office (HBO) ja inglaste BBC. Esimest osa "Varastatud kotkas" näitas HBO 28. augustil. Kolme esimese osa režissöör on Michael Apted, stsenaariumi eest vastutab Bruno Heller

  7. The treatment of late radiation effects with hyperbaric oxygenation (HBO)

    International Nuclear Information System (INIS)

    Plafki, C.; Carl, U.M.; Glag, M.; Hartmann, K.A.

    1998-01-01

    Background: Late radiation injuries may impose a negative influence on the quality of life in the affected patients. In several entities, standardized treatment protocols are lacking. Hyperbaric oxygenation (HBO) has been shown to have beneficial effects in the treatment of late radiation sequelae. Material and methods: The basic principles of HBO are reviewed as well as clinical issues. Current study protocols are presented. Results: During HBO-therapy the patient breathes pure oxygen at pressures above 100 kPa. The oxygen solubility within the fluid phase of the blood is largely increased. Biological effects include an increased oxygen diffusibility, improved collagen synthesis and neoangiogenesis as well as an enhancement of antimicrobial defenses. By decreasing the capillary filtration pressure a reduction of edema becomes possible. HBO has been shown to prevent complications following surgery in irradiated tissues. Its efficacy as an adjunct in the treatment of osteonecroses in radiation patients could be demonstrated. In addition, the loss of osseointegrated implants in the maxillofacial bones of these patients could be significantly reduced. Further indications include soft tissue necroses, hemorrhagic cystitis and proctitis in tumor patients that have been treated by radiotherapy as part of a multimodality approach. Conclusions: HBO in the treatment of late radiation effects is still subject of investigation, but remarkable results have been reported. Optimized treatment protocols need to be determined in various entities. The rate of side effects is acceptable low. (orig.) [de

  8. Dysregulation of Histone Acetyltransferases and Deacetylases in Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Yonggang Wang

    2014-01-01

    Full Text Available Cardiovascular disease (CVD remains a leading cause of mortality worldwide despite advances in its prevention and management. A comprehensive understanding of factors which contribute to CVD is required in order to develop more effective treatment options. Dysregulation of epigenetic posttranscriptional modifications of histones in chromatin is thought to be associated with the pathology of many disease models, including CVD. Histone acetyltransferases (HATs and deacetylases (HDACs are regulators of histone lysine acetylation. Recent studies have implicated a fundamental role of reversible protein acetylation in the regulation of CVDs such as hypertension, pulmonary hypertension, diabetic cardiomyopathy, coronary artery disease, arrhythmia, and heart failure. This reversible acetylation is governed by enzymes that HATs add or HDACs remove acetyl groups respectively. New evidence has revealed that histone acetylation regulators blunt cardiovascular and related disease states in certain cellular processes including myocyte hypertrophy, apoptosis, fibrosis, oxidative stress, and inflammation. The accumulating evidence of the detrimental role of histone acetylation in cardiac disease combined with the cardioprotective role of histone acetylation regulators suggests that the use of histone acetylation regulators may serve as a novel approach to treating the millions of patients afflicted by cardiac diseases worldwide.

  9. 15-Deoxy-{Delta}{sup 12,14}-prostaglandin J{sub 2} impairs the functions of histone acetyltransferases through their insolubilization in cells

    Energy Technology Data Exchange (ETDEWEB)

    Hironaka, Asako [Department of Biochemistry, Nara Medical University, Shijo-Cho 840, Kashihara, Nara 634-8521 (Japan); Morisugi, Toshiaki; Kawakami, Tetsuji [Department of Oral and Maxillofacial Surgery, Nara Medical University, Shijo-Cho 840, Kashihara, Nara 634-8521 (Japan); Miyagi, Ikuko [Laboratory of Biometabolic Chemistry, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-Cho, Okinawa 903-0215 (Japan); Tanaka, Yasuharu, E-mail: yatanaka@med.u-ryukyu.ac.jp [Laboratory of Biometabolic Chemistry, School of Health Sciences, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-Cho, Okinawa 903-0215 (Japan)

    2009-12-11

    The cyclopentenonic prostaglandin 15-deoxy-{Delta}{sup 12,14}-PG J{sub 2} (15d-PGJ{sub 2}) is a metabolite derived from PGD{sub 2}. Although 15d-PGJ{sub 2} has been demonstrated to be a potent ligand for peroxisome proliferator activated receptor {gamma} (PPAR{gamma}), the functions are not fully understood. In order to examine the effect of 15d-PGJ{sub 2} on histone acetyltransferases (HATs), several lines of cell including mouse embryonic fibroblast (MEF) cells were exposed to 15d-PGJ{sub 2}. Three types of HAT, p300, CREB-binding protein (CBP), and p300/CBP-associated factor (PCAF), selectively disappeared from the soluble fraction in time- and dose-dependent manners. Inversely, HATs in the insoluble fraction increased, suggesting their conformational changes. The decrease in the soluble form of HATs resulted in the attenuation of NF-{kappa}B-, p53-, and heat shock factor-dependent reporter gene expressions, implying that the insoluble HATs are inactive. The resultant insoluble PCAF and p300 seemed to be digested by proteasome, because proteasome inhibitors caused the accumulation of insoluble HATs. Taken together, these results indicate that 15d-PGJ{sub 2} attenuates some gene expressions that require HATs. This inhibitory action of 15d-PGJ{sub 2} on the function of HATs was independent of PPAR{gamma}, because PPAR{gamma} agonists could not mimick 15d-PGJ{sub 2} and PPAR{gamma} antagonists did not inhibit 15d-PGJ{sub 2}.

  10. Contribution of hyperbaric oxygen therapy (HBO) to the treatment of radiation necrosis

    International Nuclear Information System (INIS)

    Michaud, A.; Mongredien-Taburet, H.; Barthelemy, L.; Bellet-Barthas, M.; Morvan, R.

    1985-01-01

    Twenty-two cases of radiation necrosis were treated in the multiplace hyperbaric chamber of Brest hospital: six osteoradionecrosis and sixteen soft tissue radionecrosis. Five times HBO was used as an adjunct of surgery, antibiotherapy and local care; four times only it was used as an integral part of a complete schedule, associating in a deliberate and well thought out way the different components of the treatment. 15 patients (68%) completely healed, 2 times (9%) HBO was uneffective, and 5 times (23%) the treatments, prematurely stopped for different reasons, must be considered as not significant. The authors insist on the following points: - HBO is a simple, cheap, logical and effective treatment of an illness the physicians are helpless to cure till now; - HBO (one treatment once a day at 2.5 and 2.0 ATA pure oxygen for one hour, five days in a week) must be carried on for a long time (one series or more, 25 to 30 treatments each); - HBO must be used, at least as an adjunct of surgery, well suited antibiotherapy and local care, or preferably as a part of a multistage protocol, associating in varied proportions, depending on the stage, the different components of the treatment, the typical example being the one given by the schedule of Marx for the treatment of osteoradionecrosis of the mandible [fr

  11. Induction of spermidine/spermine N1-acetyltransferase by methylglyoxal bis(guanylhydrazone).

    Science.gov (United States)

    Pegg, A E; Erwin, B G; Persson, L

    1985-10-17

    The anti-tumor agent methylglyoxal bis(guanylhydrazone) was found to be a competitive inhibitor of spermidine/spermine N1-acetyltransferase with a Ki of about 8 microM. Treatment of rats with this drug lead to a very large increase in the total amount of spermidine/spermine N1-acetyltransferase in liver, kidney and spleen. The total increase as measured using a specific antiserum amounted to 700-fold in liver and 100-fold in kidney within 18 h of treatment with 80 mg/kg doses. At least part of this induction was due to a pronounced increase in the half-life of the acetyltransferase which increased from 15 min to more than 12 h. The very large increase in the amount of the enzyme is likely to overwhelm the direct inhibition, and a net increase in the acetylation of polyamines by this enzyme would be expected to occur after treatment with methylglyoxal bis(guanylhydrazone). The acetylated polyamines are known to be rapidly degraded by polyamine oxidase producing putrescine. Direct evidence that a substantial part of the increase in the content of putrescine in the liver of rats treated with methylglyoxal bis(guanylhydrazone) occurs via the induction of this acetylase/oxidase pathway was obtained. These results indicate that methylglyoxal bis(guanylhydrazone) affects cellular polyamine levels not only by means of its inhibitory effect on S-adenosylmethionine decarboxylase and diamine oxidase but also by the induction of spermidine/spermine N1-acetyltransferase. They also raise the possibility that the enormous increase in this enzyme which occurs with higher doses may contribute to the very severe toxicity of methylglyoxal bis(guanylhydrazone).

  12. 31P NMR spectroscopy and HbO2 cryospectrophotometry in prediction of tumor radioresistance caused by hypoxia.

    Science.gov (United States)

    Rofstad, E K; DeMuth, P; Fenton, B M; Ceckler, T L; Sutherland, R M

    1989-04-01

    The aim of this study was to search for possible relationships between the fraction of radiobiologically hypoxic cells in tumors and their 31P NMR spectral parameters and intracapillary HbO2 saturations. Four different tumor lines, two murine sarcomas (KHT, RIF-1) and two human ovarian carcinoma xenografts (MLS, OWI), were used. When tumor volume increased from about 200 mm3 to about 2000 mm3, hypoxic fraction increased from 12 to 23% for the KHT line, from 0.9 to 1.7% for the RIF-1 line, and from 9 to 28% for the MLS line. The OWI line showed similar hypoxic fractions at 200 (17%) and 2000 mm3 (15%). Tumor bioenergetic status decreased, that is, the inorganic phosphate (Pi) resonance increased and the phosphocreatine (PCr) and nucleoside triphosphate beta (NTP beta) resonances decreased, with increasing tumor volume for the KHT, RIF-1, and MLS lines, whereas the OWI line did not show any changes in the 31P NMR spectral parameters during tumor growth. Similarly, tumor HbO2 saturation status, that is, the fraction of vessels with HbO2 saturation above 30%, decreased with increasing tumor volume for the KHT, RIF-1, and MLS lines, but remained unchanged during tumor growth for the OWI line. Although the data indicated a relationship between hypoxic fraction and tumor bioenergetic status as well as tumor HbO2 saturation status within a specific line during tumor growth, there was no correlation between hypoxic fraction and tumor bioenergetic status or tumor HbO2 saturation status across the four tumor lines. This may have occurred because cell survival time under hypoxic stress as well as fraction of non-clonogenic, but metabolically active hypoxic cells differed among the tumor lines. This indicates that 31P NMR spectroscopy and HbO2 cryospectrophotometry data have to be supplemented with other data to be useful in prediction of tumor radioresistance caused by hypoxia.

  13. Disposition, Metabolism and Histone Deacetylase and Acetyltransferase Inhibition Activity of Tetrahydrocurcumin and Other Curcuminoids

    Directory of Open Access Journals (Sweden)

    Júlia T. Novaes

    2017-10-01

    Full Text Available Tetrahydrocurcumin (THC, curcumin and calebin-A are curcuminoids found in turmeric (Curcuma longa. Curcuminoids have been established to have a variety of pharmacological activities and are used as natural health supplements. The purpose of this study was to identify the metabolism, excretion, antioxidant, anti-inflammatory and anticancer properties of these curcuminoids and to determine disposition of THC in rats after oral administration. We developed a UHPLC–MS/MS assay for THC in rat serum and urine. THC shows multiple redistribution phases with corresponding increases in urinary excretion rate. In-vitro antioxidant activity, histone deacetylase (HDAC activity, histone acetyltransferase (HAT activity and anti-inflammatory inhibitory activity were examined using commercial assay kits. Anticancer activity was determined in Sup-T1 lymphoma cells. Our results indicate THC was poorly absorbed after oral administration and primarily excreted via non-renal routes. All curcuminoids exhibited multiple pharmacological effects in vitro, including potent antioxidant activity as well as inhibition of CYP2C9, CYP3A4 and lipoxygenase activity without affecting the release of TNF-α. Unlike curcumin and calebin-A, THC did not inhibit HDAC1 and PCAF and displayed a weaker growth inhibition activity against Sup-T1 cells. We show evidence for the first time that curcumin and calebin-A inhibit HAT and PCAF, possibly through a Michael-addition mechanism.

  14. Pedagogisch klimaat in het hbo? : Een verkenning

    NARCIS (Netherlands)

    Janneke Wubs

    2013-01-01

    In het hoger onderwijs wordt het pedagogisch klimaat veronachtzaamd. Het concept wordt niet mee in beschouwing genomen bij onderwijsinnovatie en onderwijsonderzoek. Dit artikel definieert het concept voor het hbo en werkt het uit op basis van de Zelf-Determinatie Theorie van Ryan en Deci

  15. Regulation of spermidine/spermine N1-acetyltransferase in L6 cells by polyamines and related compounds.

    Science.gov (United States)

    Erwin, B G; Pegg, A E

    1986-01-01

    Exposure of rat L6 cells in culture to exogenous polyamines led to a very large increase in the activity of spermidine/spermine N1-acetyltransferase. Spermine was more potent than spermidine in bringing about this increase, but in both cases the elevated acetyltransferase activity increased the cellular conversion of spermidine into putrescine. The N1-acetyltransferase turned over very rapidly in the L6 cells, with a half-life of 9 min after spermidine and 18 min after spermine. A wide variety of synthetic polyamine analogues also brought about a substantial induction of spermidine/spermine N1-acetyltransferase activity. These included sym-norspermidine, sym-norspermine, sym-homospermidine, N4-substituted spermidine derivatives, 1,3,6-triaminohexane, 1,4,7-triaminoheptane and deoxyspergualin, which were comparable with spermidine in their potency, and N1N8-bis(ethyl)spermidine, N1N9-bis(ethyl)homospermidine, methylglyoxal bis(guanylhydrazone), ethylglyoxal bis(guanylhydrazone) and 1,1'-[(methylethanediylidene)dinitrilo]bis(3-amino-guanidine ), which were even more active than spermidine. It is suggested that these polyamine analogues may bring about a decrease in cellular polyamines not only by inhibiting biosynthesis but by stimulating the degradation of spermidine into putrescine. PMID:3800951

  16. 30 CFR 75.1720-1 - Distinctively colored hard hats, or hard caps; identification for newly employed, inexperienced...

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Distinctively colored hard hats, or hard caps... STANDARDS-UNDERGROUND COAL MINES Miscellaneous § 75.1720-1 Distinctively colored hard hats, or hard caps; identification for newly employed, inexperienced miners. Hard hats or hard caps distinctively different in color...

  17. Inhibition of Different Histone Acetyltransferases (HATs) Uncovers Transcription-Dependent and -Independent Acetylation-Mediated Mechanisms in Memory Formation

    Science.gov (United States)

    Merschbaecher, Katja; Hatko, Lucyna; Folz, Jennifer; Mueller, Uli

    2016-01-01

    Acetylation of histones changes the efficiency of the transcription processes and thus contributes to the formation of long-term memory (LTM). In our comparative study, we used two inhibitors to characterize the contribution of different histone acetyl transferases (HATs) to appetitive associative learning in the honeybee. For one we applied…

  18. WARM SPITZER PHOTOMETRY OF THREE HOT JUPITERS: HAT-P-3b, HAT-P-4b AND HAT-P-12b

    Energy Technology Data Exchange (ETDEWEB)

    Todorov, Kamen O. [Department of Astronomy and Astrophysics, Pennsylvania State University, University Park, PA 16802 (United States); Deming, Drake [Department of Astronomy, University of Maryland at College Park, College Park, MD 20742 (United States); Knutson, Heather A. [Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125 (United States); Burrows, Adam [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Fortney, Jonathan J.; Laughlin, Gregory [Department of Astronomy and Astrophysics, University of California at Santa Cruz, Santa Cruz, CA 95064 (United States); Lewis, Nikole K. [Department of Earth, Atmospheric, and Planetary Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Cowan, Nicolas B. [Department of Physics and Astronomy, Northwestern University, Evanston, IL 60208 (United States); Agol, Eric [Department of Astronomy, University of Washington, Box 351580, Seattle, WA 98195 (United States); Desert, Jean-Michel [Astronomy Department, California Institute of Technology, Pasadena, CA 91125 (United States); Sada, Pedro V. [Department of Physics and Mathematics, University of Monterrey, Monterrey (Mexico); Charbonneau, David [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States); Langton, Jonathan [Department of Physics, Principia College, Elsah, IL 62028 (United States); Showman, Adam P. [Lunar and Planetary Laboratory, University of Arizona, Tucson, AZ 85721 (United States)

    2013-06-20

    We present Warm Spitzer/IRAC secondary eclipse time series photometry of three short-period transiting exoplanets, HAT-P-3b, HAT-P-4b and HAT-P-12b, in both the available 3.6 and 4.5 {mu}m bands. HAT-P-3b and HAT-P-4b are Jupiter-mass objects orbiting an early K and an early G dwarf star, respectively. For HAT-P-3b we find eclipse depths of 0.112%+0.015%-0.030% (3.6 micron) and 0.094%+0.016%-0.009% (4.5 {mu}m). The HAT-P-4b values are 0.142%+0.014%-0.016% (3.6 micron) and 0.122%+0.012%-0.014% 4.5 {mu}m). The two planets' photometry is consistent with inefficient heat redistribution from their day to night sides (and low albedos), but it is inconclusive about possible temperature inversions in their atmospheres. HAT-P-12b is a Saturn-mass planet and is one of the coolest planets ever observed during secondary eclipse, along with the hot Neptune GJ 436b and the hot Saturn WASP-29b. We are able to place 3{sigma} upper limits on the secondary eclipse depth of HAT-P-12b in both wavelengths: <0.042% (3.6 {mu}m) and <0.085% (4.5 {mu}m). We discuss these results in the context of the Spitzer secondary eclipse measurements of GJ 436b and WASP-29b. It is possible that we do not detect the eclipses of HAT-P-12b due to high eccentricity, but find that weak planetary emission in these wavelengths is a more likely explanation. We place 3{sigma} upper limits on the |e cos {omega}| quantity (where e is eccentricity and {omega} is the argument of periapsis) for HAT-P-3b (<0.0081) and HAT-P-4b (<0.0042), based on the secondary eclipse timings.

  19. Structure of Mesorhizobium loti arylamine N-acetyltransferase 1

    Energy Technology Data Exchange (ETDEWEB)

    Holton, Simon J. [Laboratory of Molecular Biophysics, Department of Biochemistry, Oxford University, South Parks Road, Oxford OX1 3QU (United Kingdom); Dairou, Julien [CNRS-UMR 7000, Faculté de Médecine Pitié-Salpêtrière, 105 Boulevard de l’Hôpital, 75013 Paris (France); Sandy, James [Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT (United Kingdom); Rodrigues-Lima, Fernando; Dupret, Jean-Marie [CNRS-UMR 7000, Faculté de Médecine Pitié-Salpêtrière, 105 Boulevard de l’Hôpital, 75013 Paris (France); UFR de Biochimie, Université Denis Diderot-Paris 7, 75005 Paris (France); Noble, Martin E. M. [Laboratory of Molecular Biophysics, Department of Biochemistry, Oxford University, South Parks Road, Oxford OX1 3QU (United Kingdom); Sim, Edith, E-mail: edith.sim@pharm.ox.ac.uk [Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT (United Kingdom); Laboratory of Molecular Biophysics, Department of Biochemistry, Oxford University, South Parks Road, Oxford OX1 3QU (United Kingdom)

    2005-01-01

    The crystal structure of a M. loti arylamine N-acetyltransferase 1 has been determined at 2.0 Å resolution. The arylamine N-acetyltransferase (NAT) enzymes have been found in a broad range of both eukaryotic and prokaryotic organisms. The NAT enzymes catalyse the transfer of an acetyl group from acetyl Co-enzyme A onto the terminal nitrogen of a range of arylamine, hydrazine and arylhydrazine compounds. Recently, several NAT structures have been reported from different prokaryotic sources including Salmonella typhimurium, Mycobacterium smegmatis and Pseudomonas aeruginosa. Bioinformatics analysis of the Mesorhizobium loti genome revealed two NAT paralogues, the first example of multiple NAT isoenzymes in a eubacterial organism. The M. loti NAT 1 enzyme was recombinantly expressed and purified for X-ray crystallographic studies. The purified enzyme was crystallized in 0.5 M Ca(OAc){sub 2}, 16% PEG 3350, 0.1 M Tris–HCl pH 8.5 using the sitting-drop vapour-diffusion method. A data set diffracting to 2.0 Å was collected from a single crystal at 100 K. The crystal belongs to the orthorhombic spacegroup P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 53.2, b = 97.3, c = 114.3 Å. The structure was refined to a final free-R factor of 24.8%. The structure reveals that despite low sequence homology, M. loti NAT1 shares the common fold as reported in previous NAT structures and exhibits the same catalytic triad of residues (Cys-His-Asp) in the active site.

  20. Structure of Mesorhizobium loti arylamine N-acetyltransferase 1

    International Nuclear Information System (INIS)

    Holton, Simon J.; Dairou, Julien; Sandy, James; Rodrigues-Lima, Fernando; Dupret, Jean-Marie; Noble, Martin E. M.; Sim, Edith

    2004-01-01

    The crystal structure of a M. loti arylamine N-acetyltransferase 1 has been determined at 2.0 Å resolution. The arylamine N-acetyltransferase (NAT) enzymes have been found in a broad range of both eukaryotic and prokaryotic organisms. The NAT enzymes catalyse the transfer of an acetyl group from acetyl Co-enzyme A onto the terminal nitrogen of a range of arylamine, hydrazine and arylhydrazine compounds. Recently, several NAT structures have been reported from different prokaryotic sources including Salmonella typhimurium, Mycobacterium smegmatis and Pseudomonas aeruginosa. Bioinformatics analysis of the Mesorhizobium loti genome revealed two NAT paralogues, the first example of multiple NAT isoenzymes in a eubacterial organism. The M. loti NAT 1 enzyme was recombinantly expressed and purified for X-ray crystallographic studies. The purified enzyme was crystallized in 0.5 M Ca(OAc) 2 , 16% PEG 3350, 0.1 M Tris–HCl pH 8.5 using the sitting-drop vapour-diffusion method. A data set diffracting to 2.0 Å was collected from a single crystal at 100 K. The crystal belongs to the orthorhombic spacegroup P2 1 2 1 2 1 , with unit-cell parameters a = 53.2, b = 97.3, c = 114.3 Å. The structure was refined to a final free-R factor of 24.8%. The structure reveals that despite low sequence homology, M. loti NAT1 shares the common fold as reported in previous NAT structures and exhibits the same catalytic triad of residues (Cys-His-Asp) in the active site

  1. Frequency of human bocavirus (HBoV) infection among children with febrile respiratory symptoms in Argentina, Nicaragua and Peru

    Science.gov (United States)

    Salmón‐Mulanovich, Gabriela; Sovero, Merly; Laguna‐Torres, V. Alberto; Kochel, Tadeusz J.; Lescano, Andres G.; Chauca, Gloria; Sanchez, J. Felix; Rodriguez, Francisco; Parrales, Eduardo; Ocaña, Victor; Barrantes, Melvin; Blazes, David L.; Montgomery, Joel M.

    2010-01-01

    Please cite this paper as: Salmón‐Mulanovich et al. (2010) Frequency of human bocavirus (HBoV) infection among children with febrile respiratory symptoms in Argentina, Nicaragua and Peru. Influenza and Other Respiratory Viruses 5(1), 1–5. Background  Globally, respiratory infections are the primary cause of illness in developing countries, specifically among children; however, an etiological agent for many of these illnesses is rarely identified. Objectives  Our study aimed to estimate the frequency of human bocavirus (HBoV) infection among pediatric populations in Argentina, Nicaragua and Peru. Methods  We conducted a cross‐sectional study using stored samples of an influenza‐like illness surveillance program. Irrespective of previous diagnosis, nasopharyngeal or nasal swab specimens were randomly selected and tested using real‐time PCR from three sites during 2007 from patients younger than 6 years old. Results  A total of 568 specimens from Argentina (185), Nicaragua (192) and Peru (191) were tested. The prevalence of HBoV was 10·8% (95% CI: 6·3; 15·3) in Argentina, 33·3% in Nicaragua (95% CI: 26·6; 40·1) and 25·1% in Peru (95% CI: 18·9; 31·3). Conclusions  These findings demonstrate circulation of HBoV in Argentina, Nicaragua and Peru among children with influenza‐like symptoms enrolled in a sentinel surveillance program. PMID:21138534

  2. HBO-I on tour in Silicon Valley

    NARCIS (Netherlands)

    Ir. Deny Smeets; Drs. Miranda W Valkenburg

    2005-01-01

    Wat is 'hot' en wat is 'not' in de ict? Dat was 'in a nutshell' de reden voor het HBO-I om een studiereis te maken naar het Mekka voor ict'ers: Silicon Valley. Voor VS-verhoudingen een klein gebied met relatief veel belangrijke ict-bedrijven: SUN, Intel, Oracle, Hewlett-Packard. En twee van de beste

  3. Oxybiotest project: microorganisms under pressure. Hyperbaric oxygen (HBO and simple pressure interaction on selected bacteria

    Directory of Open Access Journals (Sweden)

    Zanon Vincenzo

    2012-09-01

    Full Text Available Abstract Background HyperBaric Oxygen (HBO therapy involves exposure to pure oxygen in a pressurized room, and it is an already well-established treatment for various conditions, including those originated by serious infections. Starting from the observation of an increased number of patients who were accessing our HBO units for diseases supported from concomitant multidrug-resistant microorganisms, as well as considering the evident clinical benefit and laboratory final outcome of those patients at the end of the treatment, aim of our study was to measure, or better define at least, if there was any interaction between a hyperbaric environment and some selected microorganisms and if those positive results were due to the increased oxygen partial pressure (pO2 value or just to the increased pressure, regardless of the fraction of inspired oxygen (FiO2 applied (21÷100%. Design and methods We applied various increased pO2 values in a hyperbaric environment. Our study design was tailored in four steps to answer four specific questions, ordered in a progressive process: OxyBioTest (OBT-1,2,3, and 4. Specifically, we chose to investigate possible changes in the Minimum Inhibitory Concentration (MIC and in the Minimum Bactericidal Concentration (MBC of multi-resistant microorganisms after a single session of hyperbaric therapy. Results OBT-1 and OBT-2 provide a semi-quantitative confirmation of the bacterio-cidal and cytostatic effects of HBO. HBO is cidal only if the total exposure pressure is elevated, and cidal or cytostatic effect are not always dependent on the pO2 applied. OBT-4 has shown the adjuvant effect of HBO and antimicrobial drug against some selected bacteria. Discussion We seem allowed to hypothesize that only in case of a good approach to a lesion, permitting smaller bacterial loads thanks to surgical debridement and/or eventual antibiotic therapy for example, You can observe the clear effectiveness of the HyperBaric Oxygen (HBO

  4. Criticality in the configuration-mixed interacting boson model (1) $U(5)-\\hat{Q}(\\chi)\\cdot\\hat{Q}(\\chi)$ mixing

    CERN Document Server

    Hellemans, V; De Baerdemacker, S; Heyde, K

    2008-01-01

    The case of U(5)--$\\hat{Q}(\\chi)\\cdot\\hat{Q}(\\chi)$ mixing in the configuration-mixed Interacting Boson Model is studied in its mean-field approximation. Phase diagrams with analytical and numerical solutions are constructed and discussed. Indications for first-order and second-order shape phase transitions can be obtained from binding energies and from critical exponents, respectively.

  5. 30 CFR 77.1710-1 - Distinctively colored hard hats or hard caps; identification for newly employed, inexperienced...

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Distinctively colored hard hats or hard caps... Distinctively colored hard hats or hard caps; identification for newly employed, inexperienced miners. Hard hats or hard caps distinctively different in color from those worn by experienced miners shall be worn at...

  6. Imbalance between HAT and HDAC activities in the PBMCs of patients with ankylosing spondylitis or rheumatoid arthritis and influence of HDAC inhibitors on TNF alpha production.

    Directory of Open Access Journals (Sweden)

    Eric Toussirot

    Full Text Available OBJECTIVE: Acetylation or deacetylation of histone proteins may modulate cytokine gene transcription such as TNF alpha (TNF. We evaluated the balance between histone deacetytlase (HDAC and histone acetyltransferase (HAT in patients with rheumatoid arthritis (RA or ankylosing spondylitis (AS compared to healthy controls (HC and determined the influence of HDAC inhibitors (trichostatin A -TSA- or Sirtinol -Sirt- on these enzymatic activities and on the PBMC production of TNF. METHODS: 52 patients with RA, 21 with AS and 38 HC were evaluated. HAT and HDAC activities were measured on nuclear extracts from PBMC using colorimetric assays. Enzymatic activities were determined prior to and after ex vivo treatment of PBMC by TSA or Sirt. TNF levels were evaluated in PBMC culture supernatants in the absence or presence of TSA or Sirt. RESULTS: HAT and HDAC activities were significantly reduced in AS, while these activities reached similar levels in RA and HC. Ex vivo treatment of PBMC by HDACi tended to decrease HDAC expression in HC, but Sirt significantly reduced HAT in RA. TNF production by PBMC was significantly down-regulated by Sirt in HC and AS patients. CONCLUSION: HAT and HDAC were disturbed in AS while no major changes were found in RA. HDACi may modulate HDAC and HAT PBMC expression, especially Sirt in RA. Sirtinol was able to down regulate TNF production by PBMC in HC and AS. An imbalance between HAT and HDAC activities might provide the rationale for the development of HDACi in the therapeutic approach to inflammatory rheumatic diseases.

  7. Garcinol, a Histone Acetyltransferase Inhibitor, Radiosensitizes Cancer Cells by Inhibiting Non-Homologous End Joining

    Energy Technology Data Exchange (ETDEWEB)

    Oike, Takahiro [Division of Multistep Carcinogenesis, National Cancer Center Research Institute, Chuo-ku, Tokyo (Japan); Division of Genome Biology, National Cancer Center Research Institute, Chuo-ku, Tokyo (Japan); Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Gunma (Japan); Ogiwara, Hideaki [Division of Genome Biology, National Cancer Center Research Institute, Chuo-ku, Tokyo (Japan); Torikai, Kohta [Gunma University Heavy Ion Medical Center, Maebashi, Gunma (Japan); Nakano, Takashi [Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Gunma (Japan); Yokota, Jun [Division of Multistep Carcinogenesis, National Cancer Center Research Institute, Chuo-ku, Tokyo (Japan); Kohno, Takashi, E-mail: tkkohno@ncc.go.jp [Division of Genome Biology, National Cancer Center Research Institute, Chuo-ku, Tokyo (Japan)

    2012-11-01

    Purpose: Non-homologous end joining (NHEJ), a major pathway used to repair DNA double-strand breaks (DSBs) generated by ionizing radiation (IR), requires chromatin remodeling at DSB sites through the acetylation of histones by histone acetyltransferases (HATs). However, the effect of compounds with HAT inhibitory activities on the DNA damage response (DDR), including the NHEJ and cell cycle checkpoint, as well as on the radiosensitivity of cancer cells, remains largely unclear. Here, we investigated whether garcinol, a HAT inhibitor found in the rinds of Garcinia indica fruit (called mangosteens), has effects on DDR, and whether it can be used for radiosensitization. Methods and Materials: The following assays were used to examine the effect of garcinol on the inhibition of DSB repair, including the following: a conventional neutral comet assay; a cell-based assay recently developed by us, in which NHEJ repair of DSBs on chromosomal DNA was evaluated; the micrococcal nuclease sensitivity assay; and immunoblotting for autophosphorylation of DNA-dependent protein kinase catalytic subunit (DNA-PKcs). We assessed the effect of garcinol on the cell cycle checkpoint after IR treatment by analyzing the phosphorylation levels of checkpoint kinases CHK1 and CHK2 and histone H3, and by cell cycle profile analysis using flow cytometry. The radiosensitizing effect of garcinol was assessed by a clonogenic survival assay, whereas its effects on apoptosis and senescence were examined by annexin V and senescence-associated {beta}-galactosidase (SA-{beta}-Gal) staining, respectively. Results: We found that garcinol inhibits DSB repair, including NHEJ, without affecting cell cycle checkpoint. Garcinol radiosensitized A549 lung and HeLa cervical carcinoma cells with dose enhancement ratios (at 10% surviving fraction) of 1.6 and 1.5, respectively. Cellular senescence induced by IR was enhanced by garcinol. Conclusion: These results suggest that garcinol is a radiosensitizer that

  8. "Work smart, wear your hard hat"

    CERN Multimedia

    2003-01-01

    Falling objects and collisions are frequent occurrences in work sites and hazardous areas. Hard hats can help prevent many types of accident and can even save lives. Just imagine an 800 g spanner falling from a 13 m high scaffold onto the head of someone standing below - a nightmare scenario! The impact to the head is equivalent to that of a 5 kg weight falling from 2 metres. That is just what happened to Gerd Fetchenhauer when he was working on the UA1 experiment. Fortunately, he was wearing a hard hat at the time. "That hat saved my life," he explains. "It punched a hole right through the hat and I was a bit dazed for a couple of hours but otherwise I was OK." Since that day, Gerd Fetchenhauer, now working on CMS, is never seen on a work site without his hard hat on. Work sites have proliferated at CERN with the construction of the LHC and its detectors, and the wearing of hard hats is compulsory (not to mention life-saving). In the underground caverns and experiment halls, where gantry cranes and other h...

  9. HATS-50b through HATS-53b: Four Transiting Hot Jupiters Orbiting G-type Stars Discovered by the HATSouth Survey

    Science.gov (United States)

    Henning, Th.; Mancini, L.; Sarkis, P.; Bakos, G. Á.; Hartman, J. D.; Bayliss, D.; Bento, J.; Bhatti, W.; Brahm, R.; Ciceri, S.; Csubry, Z.; de Val-Borro, M.; Espinoza, N.; Fulton, B. J.; Howard, A. W.; Isaacson, H. T.; Jordán, A.; Marcy, G. W.; Penev, K.; Rabus, M.; Suc, V.; Tan, T. G.; Tinney, C. G.; Wright, D. J.; Zhou, G.; Durkan, S.; Lazar, J.; Papp, I.; Sari, P.

    2018-02-01

    We report the discovery of four close-in transiting exoplanets (HATS-50b through HATS-53b), discovered using the HATSouth three-continent network of homogeneous and automated telescopes. These new exoplanets belong to the class of hot Jupiters and orbit G-type dwarf stars, with brightness in the range V = 12.5–14.0 mag. While HATS-53 has many physical characteristics similar to the Sun, the other three stars appear to be metal-rich ([{Fe}/{{H}}]=0.2{--}0.3), larger, and more massive. Three of the new exoplanets, namely HATS-50b, HATS-51b, and HATS-53b, have low density (HATS-50b: 0.39+/- 0.10 {M}{{J}}, 1.130+/- 0.075 {R}{{J}}; HATS-51b: 0.768+/- 0.045 {M}{{J}}, 1.41+/- 0.19 {R}{{J}}; HATS-53b: 0.595+/- 0.089 {M}{{J}}, 1.340+/- 0.056 {R}{{J}}) and similar orbital periods (3.8297 days, 3.3489 days, 3.8538 days, respectively). Instead, HATS-52b is more dense (mass 2.24+/- 0.15 {M}{{J}} and radius 1.382+/- 0.086 {R}{{J}}) and has a shorter orbital period (1.3667 days). It also receives an intensive radiation from its parent star and, consequently, presents a high equilibrium temperature ({T}{eq}=1834+/- 73 K). HATS-50 shows a marginal additional transit feature consistent with an ultra-short-period hot super Neptune (upper mass limit 0.16 {M}{{J}}), which will be able to be confirmed with TESS photometry. The HATSouth network is operated by a collaboration consisting of Princeton University (PU), the Max Planck Institute für Astronomie (MPIA), the Australian National University (ANU), and the Pontificia Universidad Católica de Chile (PUC). The station at Las Campanas Observatory (LCO) of the Carnegie Institute is operated by PU in conjunction with PUC, the station at the High Energy Spectroscopic Survey (H.E.S.S.) site is operated in conjunction with MPIA, and the station at Siding Spring Observatory (SSO) is operated jointly with ANU. Based in part on observations made with the ESO 3.6 m, the NTT, the MPG 2.2 m and Euler 1.2 m Telescopes at the ESO Observatory in

  10. The Fusarium graminearum Histone Acetyltransferases Are Important for Morphogenesis, DON Biosynthesis, and Pathogenicity

    Directory of Open Access Journals (Sweden)

    Xiangjiu Kong

    2018-04-01

    Full Text Available Post-translational modifications of chromatin structure by histone acetyltransferase (HATs play a central role in the regulation of gene expression and various biological processes in eukaryotes. Although HAT genes have been studied in many fungi, few of them have been functionally characterized. In this study, we identified and characterized four putative HATs (FgGCN5, FgRTT109, FgSAS2, FgSAS3 in the plant pathogenic ascomycete Fusarium graminearum, the causal agent of Fusarium head blight of wheat and barley. We replaced the genes and all mutant strains showed reduced growth of F. graminearum. The ΔFgSAS3 and ΔFgGCN5 mutant increased sensitivity to oxidative and osmotic stresses. Additionally, ΔFgSAS3 showed reduced conidia sporulation and perithecium formation. Mutant ΔFgGCN5 was unable to generate any conidia and lost its ability to form perithecia. Our data showed also that FgSAS3 and FgGCN5 are pathogenicity factors required for infecting wheat heads as well as tomato fruits. Importantly, almost no Deoxynivalenol (DON was produced either in ΔFgSAS3 or ΔFgGCN5 mutants, which was consistent with a significant downregulation of TRI genes expression. Furthermore, we discovered for the first time that FgSAS3 is indispensable for the acetylation of histone site H3K4, while FgGCN5 is essential for the acetylation of H3K9, H3K18, and H3K27. H3K14 can be completely acetylated when FgSAS3 and FgGCN5 were both present. The RNA-seq analyses of the two mutant strains provide insight into their functions in development and metabolism. Results from this study clarify the functional divergence of HATs in F. graminearum, and may provide novel targeted strategies to control secondary metabolite expression and infections of F. graminearum.

  11. p27Kip1 Modulates Axonal Transport by Regulating α-Tubulin Acetyltransferase 1 Stability

    Directory of Open Access Journals (Sweden)

    Giovanni Morelli

    2018-05-01

    Full Text Available Summary: The protein p27Kip1 plays roles that extend beyond cell-cycle regulation during cerebral cortex development, such as the regulation of neuronal migration and neurite branching via signaling pathways that converge on the actin and microtubule cytoskeletons. Microtubule-dependent transport is essential for the maturation of neurons and the establishment of neuronal connectivity though synapse formation and maintenance. Here, we show that p27Kip1 controls the transport of vesicles and organelles along the axon of mice cortical projection neurons in vitro. Moreover, suppression of the p27Kip1 ortholog, dacapo, in Drosophila melanogaster disrupts axonal transport in vivo, leading to the reduction of locomotor activity in third instar larvae and adult flies. At the molecular level, p27Kip1 stabilizes the α-tubulin acetyltransferase 1, thereby promoting the acetylation of microtubules, a post-translational modification required for proper axonal transport. : Morelli et al. report that p27Kip1/Dacapo modulates the acetylation of microtubules in axons via stabilization of ATAT1, the main α-tubulin acetyltransferase. Its conditional loss leads to the reduction of bidirectional axonal transport of vesicles and mitochondria in vitro in mice and in vivo in Drosophila. Keywords: p27Kip1, dacapo, acetylation, axonal transport, ATAT1, alpha-tubulin, HDAC6, Drosophila, mouse, cerebral cortex

  12. Intracapillary HbO2 saturations in murine tumours and human tumour xenografts measured by cryospectrophotometry: relationship to tumour volume, tumour pH and fraction of radiobiologically hypoxic cells.

    Science.gov (United States)

    Rofstad, E K; Fenton, B M; Sutherland, R M

    1988-05-01

    Frequency distributions for intracapillary HbO2 saturation were determined for two murine tumour lines (KHT, RIF-1) and two human ovarian carcinoma xenograft lines (MLS, OWI) using a cryospectrophotometric method. The aim was to search for possible relationships between HbO2 saturation status and tumour volume, tumour pH and fraction of radiobiologically hypoxic cells. Tumour pH was measured by 31P NMR spectroscopy. Hypoxic fractions were determined from cell survival curves for tumours irradiated in vivo and assayed in vitro. Tumours in the volume range 100-4000 mm3 were studied and the majority of the vessels were found to have HbO2 saturations below 10%. The volume-dependence of the HbO2 frequency distributions differed significantly among the four tumour lines; HbO2 saturation status decreased with increasing tumour volume for the KHT, RIF-1 and MLS lines and was independent of tumour volume for the OWI line. The data indicated that the rate of decrease in HbO2 saturation status during tumour growth was related to the rate of development of necrosis. The volume-dependence of tumour pH was very similar to that of the HbO2 saturation status for all tumour lines. Significant correlations were therefore found between HbO2 saturation status and tumour pH, both within tumour lines and across the four tumour lines, reflecting that the volume-dependence of both parameters probably was a compulsory consequence of reduced oxygen supply conditions during tumour growth. Hypoxic fraction increased during tumour growth for the KHT, RIF-1 and MLS lines and was volume-independent for the OWI line, suggesting a relationship between HbO2 saturation status and hypoxic fraction within tumour lines. However, there was no correlation between these two parameters across the four tumour lines, indicating that the hypoxic fraction of a tumour is not determined only by the oxygen supply conditions; other parameters may also be important, e.g. oxygen diffusivity, rate of oxygen

  13. Path representation of su-hat (2){sub k} states I: Operators and particles for k=1,2

    Energy Technology Data Exchange (ETDEWEB)

    Lamy-Poirier, Joel, E-mail: jlamypoirier@perimeterinstitute.c [Departement de physique, de genie physique et d' optique, Universite Laval, Quebec, G1K 7P4 (Canada); Mathieu, Pierre, E-mail: pmathieu@phy.ulaval.c [Departement de physique, de genie physique et d' optique, Universite Laval, Quebec, G1K 7P4 (Canada)

    2011-04-11

    This is the first of two articles devoted to the analysis of the path description of the states in su-hat (2){sub k} WZW models, a representation well suited for constructive derivations of the fermionic characters. In this first article, the cases k=1,2 are treated in detail, emphasizing a different description in each case (operators vs particles). For k=1, we first prove, as a side result, the equivalence of two known path representations for the finitized su-hat (2){sub 1} states by displaying an explicit bijection. An immediate offshoot is the gain of a new and simple weighting for the (Kyoto) path representation that generalizes to level k. The bijection also suggests two operator constructions for the su-hat (2){sub 1} paths, a local and a nonlocal one, both interrelated. These are formal operators that map a path to another path, so that any path can be obtained by successive applications of these operators on a simple reference (ground-state) path. The nonlocal operator description is the starting point for a direct and elementary derivation of the su-hat (2){sub 1} spinon character. The second part presents an extensive study of the su-hat (2){sub 2} paths from their particle point of view, where the particles are defined as the path building blocks. The resulting generating functions appear to provide new (at least superficially) fermionic forms of the characters. In particular, a nice relationship between the sum of the j=0,1 characters at k=2 and the two ones at k=1 is unraveled.

  14. An abnormally slow proton transfer reaction in a simple HBO derivative due to ultrafast intramolecular-charge transfer events.

    Science.gov (United States)

    Alarcos, Noemí; Gutierrez, Mario; Liras, Marta; Sánchez, Félix; Douhal, Abderrazzak

    2015-07-07

    We report on the steady-state, picosecond and femtosecond time-resolved studies of a charge and proton transfer dye 6-amino-2-(2'-hydroxyphenyl)benzoxazole (6A-HBO) and its methylated derivative 6-amino-2-(2'-methoxyphenyl)benzoxazole (6A-MBO), in different solvents. With femtosecond resolution and comparison with the photobehaviour of 6A-MBO, we demonstrate for 6A-HBO in solution, the photoproduction of an intramolecular charge-transfer (ICT) process at S1 taking place in ∼140 fs or shorter, followed by solvent relaxation in the charge transferred species. The generated structure (syn-enol charge transfer conformer) experiences an excited-state intramolecular proton-transfer (ESIPT) reaction to produce a keto-type tautomer. This subsequent proton motion occurs in 1.2 ps (n-heptane), 14 ps (DCM) and 35 ps (MeOH). In MeOH, it is assisted by the solvent molecules and occurs through tunneling for which we got a large kinetic isotope effect (KIE) of about 13. For the 6A-DBO (deuterated sample in CD3OD) the global proton-transfer reaction takes place in 200 ps, showing a remarkable slow KIE regime. The slow ESIPT reaction in DCM (14 ps), not through tunnelling as it is not sensitive to OH/OD exchange, has however to overcome an energy barrier using intramolecular as well as solvent coordinates. The rich ESIPT dynamics of 6A-HBO in the used solutions is governed by an ICT reaction, triggered by the amino group, and it is solvent dependent. Thus, the charge injection to a 6A-HBO molecular frame makes the ICT species more stable, and the phenol group less acidic, slowing down the subsequent ESIPT reaction. Our findings bring new insights into the coupling between ICT and ESIPT reactions on the potential-energy surfaces of several barriers.

  15. Gallic Acid Decreases Inflammatory Cytokine Secretion Through Histone Acetyltransferase/Histone Deacetylase Regulation in High Glucose-Induced Human Monocytes.

    Science.gov (United States)

    Lee, Wooje; Lee, Sang Yeol; Son, Young-Jin; Yun, Jung-Mi

    2015-07-01

    Hyperglycemia contributes to diabetes and several diabetes-related complications. Gallic acid is a polyhydroxy phenolic compound found in various natural products. In this study, we investigated the effects and mechanism of gallic acid on proinflammatory cytokine secretion in high glucose-induced human monocytes (THP-1 cells). THP-1 cells were cultured under normoglycemic or hyperglycemic conditions, in the absence or presence of gallic acid. Hyperglycemic conditions significantly induced histone acetylation, nuclear factor-κB (NF-κB) activation, and proinflammatory cytokine release from THP-1 cells, whereas gallic acid suppressed NF-κB activity and cytokine release. It also significantly reduced CREB-binding protein/p300 (CBP/p300, a NF-κB coactivator) gene expression, acetylation levels, and CBP/p300 histone acetyltransferase (HAT) activity. In addition, histone deacetylase 2 (HDAC2) expression was significantly induced. These results suggest that gallic acid inhibits hyperglycemic-induced cytokine production in monocytes through epigenetic changes involving NF-κB. Therefore, gallic acid may have potential for the treatment and prevention of diabetes and its complications.

  16. Carnitine acetyltransferase

    DEFF Research Database (Denmark)

    Berg, Sofia Mikkelsen; Beck-Nielsen, Henning; Færgeman, Nils Joakim

    2017-01-01

    Carnitine acetyltransferase (CRAT) deficiency has previously been shown to result in muscle insulin resistance due to accumulation of long-chain acylcarnitines. However, differences in the acylcarnitine profile and/or changes in gene expression and protein abundance of CRAT in myotubes obtained...

  17. Hard-hat day

    CERN Multimedia

    2003-01-01

    CERN will be organizing a special information day on Friday, 27th June, designed to promote the wearing of hard hats and ensure that they are worn correctly. A new prevention campaign will also be launched.The event will take place in the hall of the Main Building from 11.30 a.m. to 2.00 p.m., when you will be able to come and try on various models of hard hat, including some of the very latest innovative designs, ask questions and pass on any comments and suggestions.

  18. Cloning, Characterization, and Expression Analysis of the Novel Acetyltransferase Retrogene Ard1b in the Mouse1

    Science.gov (United States)

    Pang, Alan Lap-Yin; Peacock, Stephanie; Johnson, Warren; Bear, Deborah H.; Rennert, Owen M.; Chan, Wai-Yee

    2009-01-01

    N-alpha-terminal acetylation is a modification process that occurs cotranslationally on most eukaryotic proteins. The major enzyme responsible for this process, N-alpha-terminal acetyltransferase, is composed of the catalytic subunit ARD1A and the auxiliary subunit NAT1. We cloned, characterized, and studied the expression pattern of Ard1b (also known as Ard2), a novel homolog of the mouse Ard1a. Comparison of the genomic structures suggests that the autosomal Ard1b is a retroposed copy of the X-linked Ard1a. Expression analyses demonstrated a testis predominance of Ard1b. A reciprocal expression pattern between Ard1a and Ard1b is also observed during spermatogenesis, suggesting that Ard1b is expressed to compensate for the loss of Ard1a starting from meiosis. Both ARD1A and ARD1B can interact with NAT1 to constitute a functional N-alpha-terminal acetyltransferase in vitro. The expression of ARD1B protein can be detected in mouse testes but is delayed until the first appearance of round spermatids. In a cell culture model, the inclusion of the long 3′ untranslated region of Ard1b leads to reduction of luciferase reporter activity, which implicates its role in translational repression of Ard1b during spermatogenesis. Our results suggest that ARD1B may have an important role in the later course of the spermatogenic process. PMID:19246321

  19. Hat cycle dynamic simulation

    International Nuclear Information System (INIS)

    Trucco, A.; Corallo, C.; Pini Prato, A.; Porro, S.

    1999-01-01

    Among the innovative cycle recently proposed in literature, the Humid Air Turbine Cycle - Hat better seems to fulfil the main energy market requirements of today: High efficiency in a large power ranger, low pollution, low specific capital cost. The previous results of an analysis at partial load and transient conditions are here presented, where the Hat plant has been simulated using the original model implemented in LEGO environment [it

  20. Cloning, Characterization, and Expression Analysis of the Novel Acetyltransferase Retrogene Ard1b in the Mouse1

    OpenAIRE

    Pang, Alan Lap-Yin; Peacock, Stephanie; Johnson, Warren; Bear, Deborah H.; Rennert, Owen M.; Chan, Wai-Yee

    2009-01-01

    N-alpha-terminal acetylation is a modification process that occurs cotranslationally on most eukaryotic proteins. The major enzyme responsible for this process, N-alpha-terminal acetyltransferase, is composed of the catalytic subunit ARD1A and the auxiliary subunit NAT1. We cloned, characterized, and studied the expression pattern of Ard1b (also known as Ard2), a novel homolog of the mouse Ard1a. Comparison of the genomic structures suggests that the autosomal Ard1b is a retroposed copy of th...

  1. Three-dimensional collagen I promotes gemcitabine resistance in vitro in pancreatic cancer cells through HMGA2-dependent histone acetyltransferase expression.

    Directory of Open Access Journals (Sweden)

    Surabhi Dangi-Garimella

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is associated with a pronounced collagen-rich stromal reaction that has been shown to contribute to chemo-resistance. We have previously shown that PDAC cells are resistant to gemcitabine chemotherapy in the collagen microenvironment because of increased expression of the chromatin remodeling protein high mobility group A2 (HMGA2. We have now found that human PDAC tumors display higher levels of histone H3K9 and H3K27 acetylation in fibrotic regions. We show that relative to cells grown on tissue culture plastic, PDAC cells grown in three-dimensional collagen gels demonstrate increased histone H3K9 and H3K27 acetylation, along with increased expression of p300, PCAF and GCN5 histone acetyltransferases (HATs. Knocking down HMGA2 attenuates the effect of collagen on histone H3K9 and H3K27 acetylation and on collagen-induced p300, PCAF and GCN5 expression. We also show that human PDAC tumors with HMGA2 demonstrate increased histone H3K9 and H3K27 acetylation. Additionally, we show that cells in three-dimensional collagen gels demonstrate increased protection against gemcitabine. Significantly, down-regulation of HMGA2 or p300, PCAF and GCN5 HATs sensitizes the cells to gemcitabine in three-dimensional collagen. Overall, our results increase our understanding of how the collagen microenvironment contributes to chemo-resistance in vitro and identify HATs as potential therapeutic targets against this deadly cancer.

  2. Long-term surveillance plan for the Mexican Hat disposal site Mexican Hat, Utah

    International Nuclear Information System (INIS)

    1997-05-01

    This long-term surveillance plan (LTSP) describes the U.S. Department of Energy's (DOE) long-term care program for the Uranium Mill Tailings Remedial Action (UMTRA) Project Mexican Hat, Utah, disposal site. The U.S. Nuclear Regulatory Commission (NRC) has developed regulations for the issuance of a general license for the custody and long-term care of UMTRA Project disposal sites in 10 CFR Part 40. The purpose of this general license is to ensure that the UMTRA Project disposal sites will be cared for in a manner that protects the public health and safety and the environment. Before each disposal site is licensed, the NRC requires the DOE to submit a site-specific LTSP. The DOE prepared this LTSP to meet this requirement for the Mexican Hat disposal site. The general license becomes effective when the NRC concurs with the DOE's determination of completion of remedial action for the disposal site and the NRC formally accepts this LTSP. This LTSP describes the long-term surveillance program the DOE will implement to ensure that the Mexican Hat disposal site performs as designed. The program is based on two distinct types of activities: (1) site inspections to identify potential threats to disposal cell integrity, and (2) monitoring of selected seeps to observe changes in flow rates and water quality. The LTSP is based on the UMTRA Project long-term surveillance program guidance and meets the requirements of 10 CFR section 40.27(b) and 40 CFR section 192.03. 18 refs., 6 figs., 1 tab

  3. Engineering assessment of inactive uranium mill tailings: Mexican Hat Site, Mexican Hat, Utah

    International Nuclear Information System (INIS)

    1981-09-01

    Ford, Bacon and Davis Utah Inc. has reevaluated the Mexican Hat site in order to revise the March 1977 engineering assessment of the problems resulting from the existence of radioactive uranium mill tailings at Mexican Hat, Utah. This engineering assessment has included the preparation of topographic maps, the performance of core drillings and radiometric measurements sufficient to determine areas and volumes of tailings and radiation exposures of individuals and nearby populations, the investigations of site hydrology and meteorology, and the evaluation and costing of alternative corrective actions. Radon gas released from the 2.2 million tons of tailings at the Mexican Hat site constitutes the most significant environmental impact, although windblown tailings and external gamma radiation also are factors. The four alternative actions presented in this engineering assessment range from millsite decontamination with the addition of 3 m of stabilization cover material to removal of the tailings to remote disposal sites and decontamination of the tailings site. Cost estimates for the four options range from about $15,200,000 for stabilization in place, to about $45,500,000 for disposal at a distance of about 16 mi. Three principal alternatives for the reprocessing of the Mexican Hat tailings were examined: heap leaching; treatment at an existing mill; and reprocessing at a new conventional mill constructed for tailings reprocessing. The cost of the uranium recovered would be about $115/lb of U 3 O 8 whether by heap leach or conventional plant processes. The spot market price for uranium was $25/lb early in 1981. Reprocessing the Mexican Hat tailings for uranium recovery is not economically attractive under present conditions

  4. HAT-P-25b

    DEFF Research Database (Denmark)

    Quinn, S.N.; Bakos, G. 'A; Hartman, J.

    2012-01-01

    We report the discovery of HAT-P-25b, a transiting extrasolar planet orbiting the V = 13.19 G5 dwarf star GSC 1788-01237, with a period P = 3.652836 +/- 0.000019 days, transit epoch Tc = 2455176.85173 +/- 0.00047 (BJD), and transit duration 0.1174 +/- 0.0017 days. The host star has mass of 1.01 +...

  5. Theoretical investigation of isomerism in dimers (HBO)2, (HBS)2, (HAlO)2 and (HAlS)2

    International Nuclear Information System (INIS)

    Zyubina, T.S.; Charkin, O.P.

    1991-01-01

    Using several basic sets and taking into account electron correlation, non-empiric calculations of the structure and relative stability of (HBO) 2 , (HBS) 2 , (HAlO) 2 and (HAlS) 2 dimers were made. Isomers of (HA) 2 Y 2 structure (A = B, Al; Y O,S) have the highest stability, isomers of A 2 (YH) 2 structure are more than 20 kcal/mol less stable. High potential barrier hampers transition frome one isomer to the other. Stability of (HA) 2 Y 2 dimer to decomposition into monomers (HAY+HAY) increases in the series HBS-HBO-HAlS-HAlO

  6. Engineering assessment of inactive uranium mill tailings: Mexican Hat site, Mexican Hat, Utah. Summary

    International Nuclear Information System (INIS)

    1981-09-01

    Ford, Bacon and Davis Utah Inc. has reevaluated the Mexican Hat site in order to revise the March 1977 engineering assessment of the problems resulting from the existence of radioactive uranium mill tailings at Mexican Hat, Utah. This engineering assessment has included the preparation of topographic maps, the performance of core drillings and radiometric measurements sufficient to determine areas and volumes of tailings and radiation exposures of individuals and nearby populations, the investigations of site hydrology and meteorology, and the investigations of site hydrology and meteorology, and the evaluation and costing of alternative corrective actions. Radon gas released from the 2.2 million tons of tailings at the Mexican Hat site constitutes the most significant environmental impact, although windblown tailings and external gamma radiation also are factors. The four alternative actions presented in this engineering assessment range from millsite decontamination with the addition of 3 m of stabilization cover material to removal of the tailings to remote disposal sites and decontamination of the tailings site. Cost estimates for the four options range from about $15,200,000 for stabilization in place, to about $45,500,000 for disposal at a distance of about 16 mi. Three principal alternatives for the reprocessing of the Mexican Hat tailings were examined: (a) heap leaching; treatment at an existing mill; and reprocessing at a new conventional mill constructed for tailings reprocessing. The cost of the uranium recovered would be about $115/lb of U 3 O 8 whether by heap leach or conventional plant processes. The spot market price for uranium was $25/lb early in 1981. Reprocessing the Mexican Hat tailings for uranium recovery is not economically attractive under present conditions

  7. FURTHER CONSTRAINTS ON THE OPTICAL TRANSMISSION SPECTRUM OF HAT-P-1b

    International Nuclear Information System (INIS)

    Montalto, M.; Santos, N. C.; Martins, J. H. C.; Figueira, P.; Alonso, R.; Iro, N.; Desidera, S.

    2015-01-01

    We report on novel observations of HAT-P-1 aimed at constraining the optical transmission spectrum of the atmosphere of its transiting hot-Jupiter exoplanet. Ground-based differential spectrophotometry was performed over two transit windows using the DOLORES spectrograph at the Telescopio Nazionale Galileo. Our measurements imply an average planet to star radius ratio equal to R p /R * = (0.1159 ± 0.0005). This result is consistent with the value obtained from recent near-infrared measurements of this object, but differs from previously reported optical measurements, being lower by around 4.4 exoplanet scale heights. Analyzing the data over five different spectral bins of ∼600 Å wide, we observed a single peaked spectrum (3.7 σ level) with a blue cutoff corresponding to the blue edge of the broad absorption wing of sodium and an increased absorption in the region in-between 6180 and 7400 Å. We also infer that the width of the broad absorption wings due to alkali metals is likely narrower than the one implied by solar abundance clear atmospheric models. We interpret the result as evidence that HAT-P-1b has a partially clear atmosphere at optical wavelengths with a more modest contribution from an optical absorber than previously reported

  8. FURTHER CONSTRAINTS ON THE OPTICAL TRANSMISSION SPECTRUM OF HAT-P-1b

    Energy Technology Data Exchange (ETDEWEB)

    Montalto, M.; Santos, N. C.; Martins, J. H. C.; Figueira, P.; Alonso, R. [Instituto de Astrofísica e Ciências do Espaço, Universidade do Porto, CAUP, Rua das Estrelas, PT4150-762 Porto (Portugal); Iro, N. [Theoretical Meteorology Group Klimacampus, University of Hamburg Grindelberg 5, D-20144, Hamburg (Germany); Desidera, S., E-mail: Marco.Montalto@astro.up.pt [INAF—Osservatorio Astronomico di Padova, Vicolo dellOsservatorio 5, Padova, I-35122 (Italy)

    2015-09-20

    We report on novel observations of HAT-P-1 aimed at constraining the optical transmission spectrum of the atmosphere of its transiting hot-Jupiter exoplanet. Ground-based differential spectrophotometry was performed over two transit windows using the DOLORES spectrograph at the Telescopio Nazionale Galileo. Our measurements imply an average planet to star radius ratio equal to R{sub p}/R{sub *} = (0.1159 ± 0.0005). This result is consistent with the value obtained from recent near-infrared measurements of this object, but differs from previously reported optical measurements, being lower by around 4.4 exoplanet scale heights. Analyzing the data over five different spectral bins of ∼600 Å wide, we observed a single peaked spectrum (3.7 σ level) with a blue cutoff corresponding to the blue edge of the broad absorption wing of sodium and an increased absorption in the region in-between 6180 and 7400 Å. We also infer that the width of the broad absorption wings due to alkali metals is likely narrower than the one implied by solar abundance clear atmospheric models. We interpret the result as evidence that HAT-P-1b has a partially clear atmosphere at optical wavelengths with a more modest contribution from an optical absorber than previously reported.

  9. Cross-section crushing behaviour of hat-sections (Part II: Analytical modelling)

    NARCIS (Netherlands)

    Hofmeyer, H.

    2005-01-01

    Hat-sections are often used to experimentally investigate building sheeting subject to a concentrated load and bending. In car doors, hat-sections are used for side-impact protection. Their crushing behaviour can partly be explained by only observing their cross-sectional behaviour [1]. This

  10. HAT-P-11: Discovery of a Second Planet and a Clue to Understanding Exoplanet Obliquities

    Science.gov (United States)

    Yee, Samuel W.; Petigura, Erik A.; Fulton, Benjamin J.; Knutson, Heather A.; Batygin, Konstantin; Bakos, Gáspár Á.; Hartman, Joel D.; Hirsch, Lea A.; Howard, Andrew W.; Isaacson, Howard; Kosiarek, Molly R.; Sinukoff, Evan; Weiss, Lauren M.

    2018-06-01

    HAT-P-11 is a mid-K dwarf that hosts one of the first Neptune-sized planets found outside the solar system. The orbit of HAT-P-11b is misaligned with the star’s spin—one of the few known cases of a misaligned planet orbiting a star less massive than the Sun. We find an additional planet in the system based on a decade of precision radial velocity (RV) measurements from Keck/High Resolution Echelle Spectrometer. HAT-P-11c is similar to Jupiter in its mass ({M}P\\sin i=1.6+/- 0.1 M J ) and orbital period (P={9.3}-0.5+1.0 year), but has a much more eccentric orbit (e = 0.60 ± 0.03). In our joint modeling of RV and stellar activity, we found an activity-induced RV signal of ∼7 {{m}} {{{s}}}-1, consistent with other active K dwarfs, but significantly smaller than the 31 {{m}} {{{s}}}-1 reflex motion due to HAT-P-11c. We investigated the dynamical coupling between HAT-P-11b and c as a possible explanation for HAT-P-11b’s misaligned orbit, finding that planet–planet Kozai interactions cannot tilt planet b’s orbit due to general relativistic precession; however, nodal precession operating on million year timescales is a viable mechanism to explain HAT-P-11b’s high obliquity. This leaves open the question of why HAT-P-11c may have such a tilted orbit. At a distance of 38 pc, the HAT-P-11 system offers rich opportunities for further exoplanet characterization through astrometry and direct imaging.

  11. HAT-P-16b

    DEFF Research Database (Denmark)

    Buchhave, Lars A.; Bakos, G. A.; Hartman, J. D.

    2010-01-01

    We report the discovery of HAT-P-16b, a transiting extrasolar planet orbiting the V = 10.8 mag F8 dwarf GSC 2792-01700, with a period P = 2.775960 ± 0.000003 days, transit epoch Tc = 2455027.59293 ± 0.00031 (BJD10), and transit duration 0.1276 ± 0.0013 days. The host star has a mass of 1.22 ± 0.0...

  12. Measurements of the UVR protection provided by hats used at school.

    Science.gov (United States)

    Gies, Peter; Javorniczky, John; Roy, Colin; Henderson, Stuart

    2006-01-01

    The importance of protection against solar ultraviolet radiation (UVR) in childhood has lead to SunSmart policies at Australian schools, in particular primary schools, where children are encouraged and in many cases required to wear hats at school. Hat styles change regularly and the UVR protection provided by some of the hat types currently used and recommended for sun protection by the various Australian state cancer councils had not been previously evaluated. The UVR protection of the hats was measured using UVR sensitive polysulphone film badges attached to different facial sites on rotating headforms. The sun protection type hats included in this study were broad-brimmed hats, "bucket hats" and legionnaires hats. Baseball caps, which are very popular, were also included. The broad-brimmed hats and bucket hats provided the most UVR protection for the six different sites about the face and head. Legionnaires hats also provided satisfactory UVR protection, but the caps did not provide UVR protection to many of the facial sites. The highest measured UVR protection factors for facial sites other than the forehead were 8 to 10, indicating that, while some hats can be effective, they need to be used in combination with other forms of UVR protection.

  13. James J. Gallagher: Man in the White Hat

    Science.gov (United States)

    Jolly, Jennifer L.; Robinson, Ann

    2014-01-01

    In classic Western movies, the good guy could be frequently identified by his trademark white Stetson hat, whereas the bad guy always wore black. James J. Gallagher wore many hats during his career that spanned over six decades; he too would be known as the "man in the white hat,"--trusted to do the right thing. From 1967 to 1970,…

  14. Insights into the phylogeny or arylamine N-acetyltransferases in fungi.

    Science.gov (United States)

    Martins, Marta; Dairou, Julien; Rodrigues-Lima, Fernando; Dupret, Jean-Marie; Silar, Philippe

    2010-08-01

    Previous studies have shown that Eumycetes fungi can acylate arylamine thanks to arylamine N-acetyltransferases, xenobiotic-metabolizing enzymes also found in animals and bacteria. In this article, we present the results of mining 96 available fungal genome sequences for arylamine N-acetyltransferase genes and propose their phylogeny. The filamentous Pezizomycotina are shown to possess many putative N-acetyltransferases, whilst these are often lacking in other fungal groups. The evolution of the N-acetyltransferases is best explained by the presence of at least one gene in the opisthokont ancestor of the fungi and animal kingdoms, followed by recurrent gene losses and gene duplications. A possible horizontal gene transfer event may have occurred from bacteria to the basidiomycetous yeast Malassezia globosa.

  15. Subregion-Specific p300 Conditional Knock-Out Mice Exhibit Long-Term Memory Impairments

    Science.gov (United States)

    Oliveira, Ana M. M.; Estevez, Marcel A.; Hawk, Joshua D.; Grimes, Shannon; Brindle, Paul K.; Abel, Ted

    2011-01-01

    Histone acetylation plays a critical role during long-term memory formation. Several studies have demonstrated that the histone acetyltransferase (HAT) CBP is required during long-term memory formation, but the involvement of other HAT proteins has not been extensively investigated. The HATs CBP and p300 have at least 400 described interacting…

  16. Long-term surveillance plan for the Mexican Hat disposal site Mexican Hat, Utah

    International Nuclear Information System (INIS)

    1997-06-01

    This long-term surveillance plan (LTSP) describes the U.S. Department of Energy's (DOE) long-term care program for the Uranium Mill Tailings Remedial Action (UMTRA) Project Mexican Hat, Utah, disposal site. This LSTP describes the long-term surveillance program the DOE will implement to ensure the Mexican Hat disposal site performs as designed and is cared for in a manner that protects the public health and safety and the environment. Before each disposal site is licensed for custody and long-term care, the Nuclear Regulatory Commission (NRC) requires the DOE to submit such a site-specific LTSP

  17. Spitzer Secondary Eclipses of HAT-P-13b

    Science.gov (United States)

    Hardy, Ryan A.; Harrington, J.; Hardin, M. R.; Madhusudhan, N.; Cubillos, P.; Blecic, J.; Bakos, G.; Hartman, J. D.

    2013-10-01

    HAT-P-13 b is a transiting hot Jupiter with a slightly eccentric orbit (e = 0.010) inhabiting a two-planet system. The two-planet arrangement provides an opportunity to probe the interior structure of HAT-P-13b. Under equilibrium-tide theory and confirmation that the apsides of planets b and c are in alignment, a measurement of the planet's eccentricity can be related to the planet's tidal Love number k2, which describes the central condensation of the planet's mass and its deformation under tidal effects. A measurement of k2 could constrain interior models of HAT-P-13b. HAT-P-13b's orbit is configured favorably for refinement of the eccentricity by secondary eclipse timing observations, which provide direct measurements of ecosω. In 2010, Spitzer observed two secondary eclipses of HAT-P-13b in the 3.6- and 4.5-μm IRAC bandpasses. We present secondary eclipse times and depths; joint models of the HAT-P-13 system that incorporate transit photometry and radial velocity data; and constraints on the atmospheric chemistry of HAT-P-13b that suggest solar-abundance composition without a thermal inversion. Spitzer is operated by the Jet Propulsion Laboratory, California Institute of Technology, under a contract with NASA, which provided support for this work. This work was supported in part by NASA Planetary Atmospheres Grant NNX13AF38G.

  18. WARM SPITZER OBSERVATIONS OF THREE HOT EXOPLANETS: XO-4b, HAT-P-6b, AND HAT-P-8b

    Energy Technology Data Exchange (ETDEWEB)

    Todorov, Kamen O. [Department of Astronomy and Astrophysics, The Pennsylvania State University, University Park, PA 16802 (United States); Deming, Drake [Planetary Systems Laboratory, NASA' s Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Knutson, Heather A. [Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125 (United States); Burrows, Adam [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 05844 (United States); Sada, Pedro V. [Department of Physics and Mathematics, University of Monterrey, Monterrey (Mexico); Cowan, Nicolas B. [Department of Physics and Astronomy, Northwestern University, Evanston, IL 60208 (United States); Agol, Eric [Department of Astronomy, University of Washington, Box 351580, Seattle, WA 98195 (United States); Desert, Jean-Michel; Charbonneau, David [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States); Fortney, Jonathan J.; Laughlin, Gregory [Department of Astronomy and Astrophysics, University of California at Santa Cruz, Santa Cruz, CA 95064 (United States); Langton, Jonathan [Department of Physics, Principia College, Elsah, IL 62028 (United States); Showman, Adam P.; Lewis, Nikole K. [Lunar and Planetary Laboratory, University of Arizona, Tucson, AZ 85721 (United States)

    2012-02-10

    We analyze Warm Spitzer/Infrared Array Camera observations of the secondary eclipses of three planets, XO-4b, HAT-P-6b, and HAT-P-8b. We measure secondary eclipse amplitudes at 3.6 {mu}m and 4.5 {mu}m for each target. XO-4b exhibits a stronger eclipse depth at 4.5 {mu}m than at 3.6 {mu}m, which is consistent with the presence of a temperature inversion. HAT-P-8b shows a stronger eclipse amplitude at 3.6 {mu}m and is best described by models without a temperature inversion. The eclipse depths of HAT-P-6b can be fitted with models with a small or no temperature inversion. We consider our results in the context of a postulated relationship between stellar activity and temperature inversion and a relationship between irradiation level and planet dayside temperature, as discussed by Knutson et al. and Cowan and Agol, respectively. Our results are consistent with these hypotheses, but do not significantly strengthen them. To measure accurate secondary eclipse central phases, we require accurate ephemerides. We obtain primary transit observations and supplement them with publicly available observations to update the orbital ephemerides of the three planets. Based on the secondary eclipse timing, we set upper boundaries for ecos ({omega}) for HAT-P-6b, HAT-P-8b, and XO-4b and find that the values are consistent with circular orbits.

  19. HAT-P-49b: a 1.7 M {sub J} planet transiting a bright 1.5 M {sub ☉} F-star

    Energy Technology Data Exchange (ETDEWEB)

    Bieryla, A.; Latham, D. W.; Buchhave, L. A.; Béky, B.; Falco, E.; Torres, G.; Noyes, R. W.; Berlind, P.; Calkins, M. C.; Esquerdo, G. A. [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States); Hartman, J. D.; Bakos, G. Á.; Bhatti, W.; Csubry, Z.; Penev, K.; De Val-Borro, M. [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Kovács, G. [Konkoly Observatory, Budapest 1121 (Hungary); Boisse, I. [Centro de Astrofísica, Universidade do Porto, Rua das Estrelas, 4150-762 Porto (Portugal); Lázár, J.; Papp, I., E-mail: abieryla@cfa.harvard.edu, E-mail: gbakos@astro.princeton.edu [Hungarian Astronomical Association (HAA), Budapest 1461 (Hungary); and others

    2014-04-01

    We report the discovery of the transiting extrasolar planet HAT-P-49b. The planet transits the bright (V = 10.3) slightly evolved F-star HD 340099 with a mass of 1.54 M {sub ☉} and a radius of 1.83 R {sub ☉}. HAT-P-49b is orbiting one of the 25 brightest stars to host a transiting planet which makes this a favorable candidate for detailed follow-up. This system is an especially strong target for Rossiter-McLaughlin follow-up due to the host star's fast rotation, 16 km s{sup –1}. The planetary companion has a period of 2.6915 days, mass of 1.73 M {sub J}, and radius of 1.41 R {sub J}. The planetary characteristics are consistent with that of a classical hot Jupiter but we note that this is the fourth most massive star to host a transiting planet with both M{sub p} and R{sub p} well determined.

  20. Atmospheric Retrievals of HAT-P-16b and WASP-11b/HAT-P-10b

    Science.gov (United States)

    McIntyre, Kathleen; Harrington, Joseph; Challener, Ryan; Lenius, Maria; Hartman, Joel D.; Bakos, Gaspar A.; Blecic, Jasmina; Cubillos, Patricio E.; Cameron, Andrew

    2018-01-01

    We report Bayesian atmospheric retrievals performed on the exoplanets HAT-P-16b and WASP-11b/HAT-P-10b. HAT-P-16b is a hot (equilibrium temperature 1626 ± 40 K, assuming zero Bond albedo and efficient energy redistribution), 4.19 ± 0.09 Jupiter-mass exoplanet orbiting an F8 star every 2.775960 ± 0.000003 days (Buchhave et al 2010). WASP-11b/HAT-P-10b is a cooler (1020 ± 17 K), 0.487 ± 0.018 Jupiter-mass exoplanet orbiting a K3 star every 3.7224747 ± 0.0000065 days (Bakos et al. 2009, co-discovered by West et al. 2008). We observed secondary eclipses of both planets using the 3.6 μm and 4.5 μm channels of the Spitzer Space Telescope's Infrared Array Camera (program ID 60003). We applied our Photometry for Orbits, Eclipses, and Transits (POET) code to produce normalized eclipse light curves, and our Bayesian Atmospheric Radiative Transfer (BART) code to constrain the temperature-pressure profiles and atmospheric molecular abundances of the two planets. Spitzer is operated by the Jet Propulsion Laboratory, California Institute of Technology, under a contract with NASA. This work was supported by NASA Planetary Atmospheres grant NNX12AI69G and NASA Astrophysics Data Analysis Program grant NNX13AF38G.

  1. Crystal structure of tabtoxin resistance protein complexed with acetyl coenzyme A reveals the mechanism for beta-lactam acetylation.

    Science.gov (United States)

    He, Hongzhen; Ding, Yi; Bartlam, Mark; Sun, Fei; Le, Yi; Qin, Xincheng; Tang, Hong; Zhang, Rongguang; Joachimiak, Andrzej; Liu, Jinyuan; Zhao, Nanming; Rao, Zihe

    2003-01-31

    Tabtoxin resistance protein (TTR) is an enzyme that renders tabtoxin-producing pathogens, such as Pseudomonas syringae, tolerant to their own phytotoxins. Here, we report the crystal structure of TTR complexed with its natural cofactor, acetyl coenzyme A (AcCoA), to 1.55A resolution. The binary complex forms a characteristic "V" shape for substrate binding and contains the four motifs conserved in the GCN5-related N-acetyltransferase (GNAT) superfamily, which also includes the histone acetyltransferases (HATs). A single-step mechanism is proposed to explain the function of three conserved residues, Glu92, Asp130 and Tyr141, in catalyzing the acetyl group transfer to its substrate. We also report that TTR possesses HAT activity and suggest an evolutionary relationship between TTR and other GNAT members.

  2. Cloning, characterization, and expression analysis of the novel acetyltransferase retrogene Ard1b in the mouse.

    Science.gov (United States)

    Pang, Alan Lap-Yin; Peacock, Stephanie; Johnson, Warren; Bear, Deborah H; Rennert, Owen M; Chan, Wai-Yee

    2009-08-01

    N-alpha-terminal acetylation is a modification process that occurs cotranslationally on most eukaryotic proteins. The major enzyme responsible for this process, N-alpha-terminal acetyltransferase, is composed of the catalytic subunit ARD1A and the auxiliary subunit NAT1. We cloned, characterized, and studied the expression pattern of Ard1b (also known as Ard2), a novel homolog of the mouse Ard1a. Comparison of the genomic structures suggests that the autosomal Ard1b is a retroposed copy of the X-linked Ard1a. Expression analyses demonstrated a testis predominance of Ard1b. A reciprocal expression pattern between Ard1a and Ard1b is also observed during spermatogenesis, suggesting that Ard1b is expressed to compensate for the loss of Ard1a starting from meiosis. Both ARD1A and ARD1B can interact with NAT1 to constitute a functional N-alpha-terminal acetyltransferase in vitro. The expression of ARD1B protein can be detected in mouse testes but is delayed until the first appearance of round spermatids. In a cell culture model, the inclusion of the long 3' untranslated region of Ard1b leads to reduction of luciferase reporter activity, which implicates its role in translational repression of Ard1b during spermatogenesis. Our results suggest that ARD1B may have an important role in the later course of the spermatogenic process.

  3. Neisseria meningitidis serogroup A capsular polysaccharide acetyltransferase, methods and compositions

    Energy Technology Data Exchange (ETDEWEB)

    Stephens, David S [Stone Mountain, GA; Gudlavalleti, Seshu K [Kensington, MD; Tzeng, Yih-Ling [Atlanta, GA; Datta, Anup K [San Diego, CA; Carlson, Russell W [Athens, GA

    2011-02-08

    Provided are methods for recombinant production of an O-acetyltransferase and methods for acetylating capsular polysaccharides, especially those of a Serogroup A Neisseria meningitidis using the recombinant O-acetyltransferase, and immunogenic compositions comprising the acetylated capsular polysaccharide.

  4. ERRATUM: Work smart, wear your hard hat

    CERN Multimedia

    2003-01-01

    An error appeared in the article «Work smart, wear your hard hat» published in Weekly Bulletin 27/2003, page 5. The impact which pierced a hole in the hard hat worn by Gerd Fetchenhauer was the equivalent of a box weighing 5 kg and not 50 kg.

  5. The GAPS programme with HARPS-N at TNG. XVI. Measurement of the Rossiter-McLaughlin effect of transiting planetary systems HAT-P-3, HAT-P-12, HAT-P-22, WASP-39, and WASP-60

    Science.gov (United States)

    Mancini, L.; Esposito, M.; Covino, E.; Southworth, J.; Biazzo, K.; Bruni, I.; Ciceri, S.; Evans, D.; Lanza, A. F.; Poretti, E.; Sarkis, P.; Smith, A. M. S.; Brogi, M.; Affer, L.; Benatti, S.; Bignamini, A.; Boccato, C.; Bonomo, A. S.; Borsa, F.; Carleo, I.; Claudi, R.; Cosentino, R.; Damasso, M.; Desidera, S.; Giacobbe, P.; González-Álvarez, E.; Gratton, R.; Harutyunyan, A.; Leto, G.; Maggio, A.; Malavolta, L.; Maldonado, J.; Martinez-Fiorenzano, A.; Masiero, S.; Micela, G.; Molinari, E.; Nascimbeni, V.; Pagano, I.; Pedani, M.; Piotto, G.; Rainer, M.; Scandariato, G.; Smareglia, R.; Sozzetti, A.; Andreuzzi, G.; Henning, Th.

    2018-05-01

    Context. The measurement of the orbital obliquity of hot Jupiters with different physical characteristics can provide clues to the mechanisms of migration and orbital evolution of this particular class of giant exoplanets. Aims: We aim to derive the degree of alignment between planetary orbit and stellar spin angular momentum vectors and look for possible links with other orbital and fundamental physical parameters of the star-planet system. We focus on the characterisation of five transiting planetary systems (HAT-P-3, HAT-P-12, HAT-P-22, WASP-39, and WASP-60) and the determination of their sky-projected planet orbital obliquity through the measurement of the Rossiter-McLaughlin effect. Methods: We used HARPS-N high-precision radial velocity measurements, gathered during transit events, to measure the Rossiter-McLaughlin effect in the target systems and determine the sky-projected angle between the planetary orbital plane and stellar equator. The characterisation of stellar atmospheric parameters was performed by exploiting the HARPS-N spectra, using line equivalent width ratios and spectral synthesis methods. Photometric parameters of the five transiting exoplanets were re-analysed through 17 new light curves, obtained with an array of medium-class telescopes, and other light curves from the literature. Survey-time-series photometric data were analysed for determining the rotation periods of the five stars and their spin inclination. Results: From the analysis of the Rossiter-McLaughlin effect we derived a sky-projected obliquity of λ = 21.2° ± 8.7°, λ = -54°-13°+41°, λ = -2.1° ± 3.0°, λ = 0° ± 11°, and λ = -129° ± 17° for HAT-P-3 b, HAT-P-12 b, HAT-P-22 b, WASP-39 b, and WASP-60 b, respectively. The latter value indicates that WASP-60 b is moving on a retrograde orbit. These values represent the first measurements of λ for the five exoplanetary systems under study. The stellar activity of HAT-P-22 indicates a rotation period of 28.7 ± 0

  6. Acetyltransferases and tumour suppression

    International Nuclear Information System (INIS)

    Phillips, A C; Vousden, Karen H

    2000-01-01

    The acetyltransferase p300 was first identified associated with the adenoviral transforming protein E1A, suggesting a potential role for p300 in the regulation of cell proliferation. Direct evidence demonstrating a role for p300 in human tumours was lacking until the recentl publication by Gayther et al, which strongly supports a role for p300 as a tumour suppressor. The authors identify truncating mutations associated with the loss or mutation of the second allele in both tumour samples and cell lines, suggesting that loss of p300 may play a role in the development of a subset of human cancers

  7. Crystal structure of tabtoxin resistance protein complexed with acetyl coenzyme A reveals the mechanism for {beta}-lactam acetylation.

    Energy Technology Data Exchange (ETDEWEB)

    He, H.; Ding, Y.; Bartlam, M.; Sun, F.; Le, Y.; Qin, X.; Tang, H.; Zhang, R.; Joachimiak, A.; Liu, J.; Zhao, N.; Rao, Z.; Biosciences Division; Tsinghua Univ.; Chinese Academy of Science

    2003-01-31

    Tabtoxin resistance protein (TTR) is an enzyme that renders tabtoxin-producing pathogens, such as Pseudomonas syringae, tolerant to their own phytotoxins. Here, we report the crystal structure of TTR complexed with its natural cofactor, acetyl coenzyme A (AcCoA), to 1.55 {angstrom} resolution. The binary complex forms a characteristic 'V' shape for substrate binding and contains the four motifs conserved in the GCN5-related N-acetyltransferase (GNAT) superfamily, which also includes the histone acetyltransferases (HATs). A single-step mechanism is proposed to explain the function of three conserved residues, Glu92, Asp130 and Tyr141, in catalyzing the acetyl group transfer to its substrate. We also report that TTR possesses HAT activity and suggest an evolutionary relationship between TTR and other GNAT members.

  8. FACTORS & ELEMENTAL ANALYSIS OF SIX THINKING HATS TECHNIQUE USING ABCD FRAMEWORK

    OpenAIRE

    Dr. P. S. Aithal; V. T. Shailashree; Dr. P. M. Suresh Kumar

    2017-01-01

    De Bono's Six Thinking Hats technique suggests different types of thinking corresponding to six thinking roles for the analyst, associated with hats of six different colors. The technique correlates different thinking styles used in a systematic problem solving procedure with different coloured hats. Alternately, by conceptualizing each type of hat, the person focuses on the style of thinking associated with each colour so that the problem can be analysed from different angles and frame of re...

  9. Mechanism by which arylamine N-acetyltransferase 1 ablation causes insulin resistance in mice

    DEFF Research Database (Denmark)

    Camporez, João Paulo; Wang, Yongliang; Faarkrog, Kasper

    2017-01-01

    A single-nucleotide polymorphism in the human arylamine N-acetyltransferase 2 (Nat2) gene has recently been identified as associated with insulin resistance in humans. To understand the cellular and molecular mechanisms by which alterations in Nat2 activity might cause insulin resistance, we...... examined murine ortholog Nat1 knockout (KO) mice. Nat1 KO mice manifested whole-body insulin resistance, which could be attributed to reduced muscle, liver, and adipose tissue insulin sensitivity. Hepatic and muscle insulin resistance were associated with marked increases in both liver and muscle...... adipose tissue, and hepatocytes. Taken together, these studies demonstrate that Nat1 deletion promotes reduced mitochondrial activity and is associated with ectopic lipid-induced insulin resistance. These results provide a potential genetic link among mitochondrial dysfunction with increased ectopic lipid...

  10. 'Nederlandismes' in HAT

    Directory of Open Access Journals (Sweden)

    F. van Houwelingen

    1998-04-01

    Full Text Available Dutch influence in HAT (1994 Although there is consensus among linguists that Afrikaans and Dutch are related languages, and that Afrikaans originated from 17th century Dutch, the differences between present-day varieties of Afrikaans and Dutch serve as proof that we are dealing with two separate languages. These differences should be clearly visible in descriptive as well as normative sources of the two languages. However, the third edition of Verklarende Handewoordeboek van die Afrikaanse Taal (HAT, one of the leading Afrikaans standard monolingual dictionaries, contains headwords as well as microstructural information that do not agree with the reality of the Afrikaans of today. An empirical investigation conducted among Afrikaans-speaking dictionary users has proven that a significant Dutch influence is still prominent - in the micro- as well as the macrostructure of the dictionary. It is believed that the Dutch "thread" of many Afrikaans dictionaries has indirectly contributed towards the creation of a super-standard norm, which is partially responsible for the estrangement between the cultural language and the vernacular.

  11. Kavunda ebeveyn hat ile melezlerinin bazı tohum ve tohum çıkışı özelliklerinin belirlenmesi

    OpenAIRE

    TUR, Ayşegül; SEYMEN, Musa; TÜRKMEN, Önder

    2018-01-01

    Bu çalışma, 2015-2016 yıllarında yürütülmüş ve bitkisel materyal olarak, 13 genotip (SÇ-1: Sel-1-1. SÇ-2: Sel-1-2. SÇ-3: Sel-2. SÇ-4: Sel-3. SÇ-5: Sel-4. SÇ-6: Sel-6-1. SÇ-7: Sel-6-2. SÇ-8: Sel-7. SÇ-9: Sel-8. SÇ-10: Sel-9. SÇ-11: Sel-10. SÇ-12: Sel-11. SÇ-13: Pop. Diyarbakır). 4 ebeveyn hat (EB-1: saf hat-7. EB-2: saf hat-A4. EB-3: saf hat-G22. EB-4: saf hat-136) ve 9 melez (M-1: safhat 7xsafhat-136. M-2: safhat-7xsafhat-A4. M-3: safhat-7xsafhat-G22. M-4: safhat-G22xsafhat-136. M-5: safhat-G...

  12. Crystallization and preliminary X-ray diffraction analysis of PAT, an acetyltransferase from Sulfolobus solfataricus

    International Nuclear Information System (INIS)

    Cho, Ching-Chang; Luo, Ching-Wei; Hsu, Chun-Hua

    2008-01-01

    PAT, an acetyltransferase from the archaeon S. solfataricus that specifically acetylates the chromatin protein Alba, was expressed, purified and crystallized. PAT is an acetyltransferase from the archaeon Sulfolobus solfataricus that specifically acetylates the chromatin protein Alba. The enzyme was expressed, purified and subsequently crystallized using the sitting-drop vapour-diffusion technique. Native diffraction data were collected to 1.70 Å resolution on the BL13C1 beamline of NSRRC from a flash-frozen crystal at 100 K. The crystals belonged to space group P2 1 2 1 2 1 , with unit-cell parameters a = 44.30, b = 46.59, c = 68.39 Å

  13. HAT-P-10b: A LIGHT AND MODERATELY HOT JUPITER TRANSITING A K DWARF

    International Nuclear Information System (INIS)

    Bakos, G. A.; Pal, A.; Torres, G.; Sipocz, B.; Latham, D. W.; Noyes, R. W.; Hartman, J.; Esquerdo, G. A.; Sasselov, D. D.; Kovacs, Gabor; Stefanik, R. P.; Kovacs, Geza; Fischer, D. A.; Johnson, J. A.; Marcy, G. W.; Howard, A. W.; Butler, R. P.; Lazar, J.; Papp, I.; Sari, P.

    2009-01-01

    We report on the discovery of HAT-P-10b, one of the lowest mass (0.487 ± 0.018 M J ) transiting extrasolar planets (TEPs) discovered to date by transit searches. HAT-P-10b orbits the moderately bright V = 11.89 K dwarf GSC 02340-01714, with a period P = 3.7224747 ± 0.0000065 days, transit epoch T c = 2454759.68683 ± 0.00016 (BJD), and duration 0.1090 ± 0.0008 days. HAT-P-10b has a radius of 1.005 +0.032 -0.027 R J yielding a mean density of 0.594 ± 0.052 g cm -3 . Comparing these observations with recent theoretical models we find that HAT-P-10b is consistent with a ∼4.5 Gyr, almost pure hydrogen and helium gas giant planet with a 10 M + core. With an equilibrium temperature of T eq = 1020 ± 17 K, HAT-P-10b is one of the coldest TEPs. Curiously, its Safronov number θ = 0.053 ± 0.002 falls close to the dividing line between the two suggested TEP populations.

  14. All Adventurous Women Do: HPV, Narrative, and HBO's Girls.

    Science.gov (United States)

    Rogers, Brian

    2016-01-01

    This study looks at media portrayals of sexual health through the popular HBO television show Girls. This rhetorical criticism of Girls delineates two emergent narrative themes. First, the show repeatedly discusses human papillomavirus (HPV) in terms of its severity, but it oscillates in terms of representing the degree of significance. Second, the show frames the source of infection as more important than other concerns related to HPV. Ultimately, this analysis demonstrates that Girls perpetuates a problematic narrative plot structure related to issues of HPV transmission; it also provides a largely scientifically accurate portrayal of HPV and promotes open and frank discussions of sexual health. It is argued that mediated narratives, such as Girls, might have the potential to transform social attitudes and actions and should thereby garner attention from health communication scholars and public health advocates.

  15. Application of Six Thinking Hats with the Theme „Profession of Sociologist”. Transcript of the Sequence of Green Hat

    Directory of Open Access Journals (Sweden)

    Gheorghe Onuţ

    2009-12-01

    Full Text Available The study is the transcription of the sequence of green hat from the application of the creative technique Six Thinking Hats (Edward de Bono’s creation that I did at the workshop with the theme „Profession of Sociologist”, of the international colloquium of social sciences ACUM 2008. The colloquium ACUM is the most important of the scientific manifestations organized by the Faculty of Law and Sociology of „Transilvania” University of Braşov.

  16. Phosphinothricin Acetyltransferases Identified Using In Vivo, In Vitro, and Bioinformatic Analyses

    Science.gov (United States)

    VanDrisse, Chelsey M.; Hentchel, Kristy L.

    2016-01-01

    ABSTRACT Acetylation of small molecules is widespread in nature, and in some cases, cells use this process to detoxify harmful chemicals. Streptomyces species utilize a Gcn5 N-acetyltransferase (GNAT), known as Bar, to acetylate and detoxify a self-produced toxin, phosphinothricin (PPT), a glutamate analogue. Bar homologues, such as MddA from Salmonella enterica, acetylate methionine analogues such as methionine sulfoximine (MSX) and methionine sulfone (MSO), but not PPT, even though Bar homologues are annotated as PPT acetyltransferases. S. enterica was used as a heterologous host to determine whether or not putative PPT acetyltransferases from various sources could acetylate PPT, MSX, and MSO. In vitro and in vivo analyses identified substrates acetylated by putative PPT acetyltransferases from Deinococcus radiodurans (DR_1057 and DR_1182) and Geobacillus kaustophilus (GK0593 and GK2920). In vivo, synthesis of DR_1182, GK0593, and GK2920 blocked the inhibitory effects of PPT, MSX, and MSO. In contrast, DR_1057 did not detoxify any of the above substrates. Results of in vitro studies were consistent with the in vivo results. In addition, phylogenetic analyses were used to predict the functionality of annotated PPT acetyltransferases in Burkholderia xenovorans, Bacillus subtilis, Staphylococcus aureus, Acinetobacter baylyi, and Escherichia coli. IMPORTANCE The work reported here provides an example of the use of a heterologous system for the identification of enzyme function. Many members of this superfamily of proteins do not have a known function, or it has been annotated solely on the basis of sequence homology to previously characterized enzymes. The critical role of Gcn5 N-acetyltransferases (GNATs) in the modulation of central metabolic processes, and in controlling metabolic stress, necessitates approaches that can reveal their physiological role. The combination of in vivo, in vitro, and bioinformatics approaches reported here identified GNATs that can

  17. Become a CERN WhiteHat

    CERN Multimedia

    CERN. Geneva

    2014-01-01

    Discovering CERN's weaknesses is as important as ever. Become a CERN WhiteHat and help us poking around CERN computing services and web applications. All you need is to apply and get the appropriate training...

  18. Incidence of Hospital Acquired Thrombosis (HAT) in a Tertiary Care Hospital.

    LENUS (Irish Health Repository)

    Khan, MI

    2017-04-01

    Venous thromboembolism (VTE) is a major cause of preventable morbidity and mortality in hospitalized patients. In spite of guidelines, VTE prophylaxis continues to be underutilised, and hospital acquired thrombosis (HAT) continues to be a problem. This study was conducted to estimate the incidence of HAT in a tertiary referral centre and to examine whether VTE risk assessment and thromboprophylaxis (TP) were implemented. Patients 18 years and above, with a radiologically-confirmed acute VTE during the study period of 15 weeks were included. Acute VTE was diagnosed in 100 patients and HAT was diagnosed in 48. There were 12,024 admissions over the study period, therefore the incidence of HAT was 0.4%. TP was prescribed in only 35% of patients, and 65% did not receive any or appropriate TP. Hospitals without active implementation of a formal risk assessment tool and TP policy are likely to continue to have increased incidence of HAT.

  19. Structure of a putative acetyltransferase (PA1377) from Pseudomonas aeruginosa

    International Nuclear Information System (INIS)

    Davies, Anna M.; Tata, Renée; Chauviac, François-Xavier; Sutton, Brian J.; Brown, Paul R.

    2008-01-01

    The crystal structure of an acetyltransferase encoded by the gene PA1377 from Pseudomonas aeruginosa has been determined at 2.25 Å resolution. Comparison with a related acetyltransferase revealed a structural difference in the active site that was taken to reflect a difference in substrate binding and/or specificity between the two enzymes. Gene PA1377 from Pseudomonas aeruginosa encodes a 177-amino-acid conserved hypothetical protein of unknown function. The structure of this protein (termed pitax) has been solved in space group I222 to 2.25 Å resolution. Pitax belongs to the GCN5-related N-acetyltransferase family and contains all four sequence motifs conserved among family members. The β-strand structure in one of these motifs (motif A) is disrupted, which is believed to affect binding of the substrate that accepts the acetyl group from acetyl-CoA

  20. The elliptic quantum algebra Uq,p(sl-hatN) and its vertex operators

    International Nuclear Information System (INIS)

    Chang Wenjing; Ding Xiangmao

    2009-01-01

    We construct a realization of the elliptic quantum algebra U q,p (sl-hat N ) for any given level k in terms of free boson fields and their twisted partners. It can be considered as the elliptic deformation of the Wakimoto realization of the quantum affine algebra U q (sl-hat N ). We also construct a family of screening currents, which commute with the currents of U q,p (sl-hat N ) up to total q-differences. And we give explicit twisted expressions for the type I and type II vertex operators of U q,p (sl-hat N ) by twisting the known results of the type I vertex operators of the quantum affine algebra U q (sl-hat N ) and the new results of the type II vertex operators of U q (sl-hat N ) we obtained in this paper.

  1. HATS-43b, HATS-44b, HATS-45b, and HATS-46b: Four Short-period Transiting Giant Planets in the Neptune–Jupiter Mass Range

    Science.gov (United States)

    Brahm, R.; Hartman, J. D.; Jordán, A.; Bakos, G. Á.; Espinoza, N.; Rabus, M.; Bhatti, W.; Penev, K.; Sarkis, P.; Suc, V.; Csubry, Z.; Bayliss, D.; Bento, J.; Zhou, G.; Mancini, L.; Henning, T.; Ciceri, S.; de Val-Borro, M.; Shectman, S.; Crane, J. D.; Arriagada, P.; Butler, P.; Teske, J.; Thompson, I.; Osip, D.; Díaz, M.; Schmidt, B.; Lázár, J.; Papp, I.; Sári, P.

    2018-03-01

    We report the discovery of four short-period extrasolar planets transiting moderately bright stars from photometric measurements of the HATSouth network coupled to additional spectroscopic and photometric follow-up observations. While the planet masses range from 0.26 to 0.90 {M}{{J}}, the radii are all approximately a Jupiter radii, resulting in a wide range of bulk densities. The orbital period of the planets ranges from 2.7 days to 4.7 days, with HATS-43b having an orbit that appears to be marginally non-circular (e = 0.173 ± 0.089). HATS-44 is notable for having a high metallicity ([{Fe}/{{H}}] = 0.320 ± 0.071). The host stars spectral types range from late F to early K, and all of them are moderately bright (13.3 Carnegie Institute is operated by PU in conjunction with PUC, the station at the High Energy Spectroscopic Survey (H.E.S.S.) site is operated in conjunction with MPIA, and the station at Siding Spring Observatory (SSO) is operated jointly with ANU. This paper includes data gathered with the MPG 2.2 m and ESO 3.6 m telescopes at the ESO Observatory in La Silla. This paper includes data gathered with the 6.5 meter Magellan Telescopes located at Las Campanas Observatory, Chile.

  2. How a hat may affect 3-month-olds' recognition of a face: an eye-tracking study.

    Science.gov (United States)

    Bulf, Hermann; Valenza, Eloisa; Turati, Chiara

    2013-01-01

    Recent studies have shown that infants' face recognition rests on a robust face representation that is resilient to a variety of facial transformations such as rotations in depth, motion, occlusion or deprivation of inner/outer features. Here, we investigated whether 3-month-old infants' ability to represent the invariant aspects of a face is affected by the presence of an external add-on element, i.e. a hat. Using a visual habituation task, three experiments were carried out in which face recognition was investigated by manipulating the presence/absence of a hat during face encoding (i.e. habituation phase) and face recognition (i.e. test phase). An eye-tracker system was used to record the time infants spent looking at face-relevant information compared to the hat. The results showed that infants' face recognition was not affected by the presence of the external element when the type of the hat did not vary between the habituation and test phases, and when both the novel and the familiar face wore the same hat during the test phase (Experiment 1). Infants' ability to recognize the invariant aspects of a face was preserved also when the hat was absent in the habituation phase and the same hat was shown only during the test phase (Experiment 2). Conversely, when the novel face identity competed with a novel hat, the hat triggered the infants' attention, interfering with the recognition process and preventing the infants' preference for the novel face during the test phase (Experiment 3). Findings from the current study shed light on how faces and objects are processed when they are simultaneously presented in the same visual scene, contributing to an understanding of how infants respond to the multiple and composite information available in their surrounding environment.

  3. The "Burgundian" hat from Herjolfsnes, Greenland: new discoveries, new dates

    DEFF Research Database (Denmark)

    Smith, Michèle Hayeur; Arneborg, Jette; Smith, Kevin

    2016-01-01

    of the Greenland Norse colony but also its enduring cultural links with continental European fashions, following a comment to this effect published by Nørlund himself. In 1996, the hat was dated to the early fourteenth century by Arneborg, a century earlier than Nørlund’s dating, based on stylistic comparisons...... with European examples. Recent research on North Atlantic textiles led to a re-examination of the hat, with different sections sampled and resubmitted for accelerated mass spectrometry dating. The results suggest that the body of the hat and its crown are of different periods with c. 100 years between them...

  4. SPITZER IRAC SECONDARY ECLIPSE PHOTOMETRY OF THE TRANSITING EXTRASOLAR PLANET HAT-P-1b

    International Nuclear Information System (INIS)

    Todorov, Kamen; Deming, Drake; Harrington, Jospeph; Stevenson, Kevin B.; Bowman, William C.; Nymeyer, Sarah; Fortney, Jonathan J.; Bakos, Gaspar A.

    2010-01-01

    We report Spitzer/IRAC photometry of the transiting giant exoplanet HAT-P-1b during its secondary eclipse. This planet lies near the postulated boundary between the pM and pL-class of hot Jupiters, and is important as a test of models for temperature inversions in hot Jupiter atmospheres. We derive eclipse depths for HAT-P-1b, in units of the stellar flux, that are: 0.080% ± 0.008% [3.6 μm], 0.135% ± 0.022% [4.5 μm], 0.203% ± 0.031% [5.8 μm], and 0.238% ± 0.040% [8.0 μm]. These values are best fit using an atmosphere with a modest temperature inversion, intermediate between the archetype inverted atmosphere (HD 209458b) and a model without an inversion. The observations also suggest that this planet is radiating a large fraction of the available stellar irradiance on its dayside, with little available for redistribution by circulation. This planet has sometimes been speculated to be inflated by tidal dissipation, based on its large radius in discovery observations, and on a non-zero orbital eccentricity allowed by the radial velocity data. The timing of the secondary eclipse is very sensitive to orbital eccentricity, and we find that the central phase of the eclipse is 0.4999 ± 0.0005. The difference between the expected and observed phase indicates that the orbit is close to circular, with a 3σ limit of |e cos ω| < 0.002.

  5. Structural and functional characterization of an arylamine N-acetyltransferase from the pathogen Mycobacterium abscessus

    DEFF Research Database (Denmark)

    Cocaign, Angélique; Kubiak, Xavier Jean Philippe; Xu, Ximing

    2014-01-01

    Mycobacterium abscessus is the most pathogenic rapid-growing mycobacterium and is one of the most resistant organisms to chemotherapeutic agents. However, structural and functional studies of M. abscessus proteins that could modify/inactivate antibiotics remain nonexistent. Here, the structural...... is endogenously expressed and functional in both the rough and smooth M. abscessus morphotypes. The crystal structure of (MYCAB)NAT1 at 1.8 Å resolution reveals that it is more closely related to Nocardia farcinica NAT than to mycobacterial isoforms. In particular, structural and physicochemical differences from...... and functional characterization of an arylamine N-acetyltransferase (NAT) from M. abscessus [(MYCAB)NAT1] are reported. This novel prokaryotic NAT displays significant N-acetyltransferase activity towards aromatic substrates, including antibiotics such as isoniazid and p-aminosalicylate. The enzyme...

  6. Prevalence and Phylogenetic Analysis of Human Bocaviruses 1-4 in Pediatric Patients with Various Infectious Diseases.

    Directory of Open Access Journals (Sweden)

    Min Zhao

    Full Text Available Viral infections caused by human bocaviruses 1-4 (HBoV1-4 are more complicated than previously believed. A retrospective, large-scale study was undertaken to explore the prevalence of HBoV1-4 in pediatric patients with various infectious diseases and delineate their phylogenetic characteristics.Clinical samples from four specimen types, including 4,941 respiratory, 2,239 cerebrospinal fluid (CSF, 2,619 serum, and 1,121 fecal specimens, collected from pediatric patients with various infectious diseases were screened for HBoV1-4. A 690-nt fragment in each specimen was then amplified and sequenced for phylogenetic analysis. Clinical characteristics of HBoV-positive patients with different specimen types available were evaluated.Approximately 1.2% of patients were confirmed as HBoV-positive, with the highest positive rate in patients with gastrointestinal infection (2.2%, followed by respiratory (1.65%, central nervous system (0.8%, and hematological infections (0.2%. A single genetic lineage of HBoV1 circulated among children over the 8-year period, while a new cluster of HBoV2, via intra-genotype recombination between HBoV2A and HBoV2B, was prevalent. Some patients had HBoV1-positive respiratory and serum specimens or fecal specimens. Several cases became HBoV1-positive following the appearance of respiratory infection, while several cases were positive for HBoV2 only in CSF and serum specimens, rather than respiratory specimens.A single genetic lineage of HBoV1 is speculated as a viral pathogen of respiratory infection and causes both comorbid infection and acute gastroenteritis. Additionally, a new cluster of HBoV2 is prevalent in China, which may infect the host through sites other than the respiratory tract.

  7. Application of Human-Autonomy Teaming (HAT) Patterns to Reduce Crew Operations (RCO)

    Science.gov (United States)

    Shively, R. Jay; Brandt, Summer L.; Lachter, Joel; Matessa, Mike; Sadler, Garrett; Battiste, Henri

    2016-01-01

    Unmanned aerial systems, robotics, advanced cockpits, and air traffic management are all examples of domains that are seeing dramatic increases in automation. While automation may take on some tasks previously performed by humans, humans will still be required, for the foreseeable future, to remain in the system. The collaboration with humans and these increasingly autonomous systems will begin to resemble cooperation between teammates, rather than simple task allocation. It is critical to understand this human-autonomy teaming (HAT) to optimize these systems in the future. One methodology to understand HAT is by identifying recurring patterns of HAT that have similar characteristics and solutions. This paper applies a methodology for identifying HAT patterns to an advanced cockpit project.

  8. Supplement to the UMTRA Project water sampling and analysis plan, Mexican Hat, Utah

    International Nuclear Information System (INIS)

    1995-09-01

    This water sampling and analysis plan (WSAP) supplement supports the regulatory and technical basis for water sampling at the Mexican Hat, Utah, Uranium Mill Tailings Remedial Action (UMTRA) Project site, as defined in the 1994 WSAP document for Mexican Hat (DOE, 1994). Further, the supplement serves to confirm our present understanding of the site relative to the hydrogeology and contaminant distribution as well as our intention to continue to use the sampling strategy as presented in the 1994 WSAP document for Mexican Hat. Ground water and surface water monitoring activities are derived from the US Environmental Protection Agency regulations in 40 CFR Part 192 (1991) and 60 FR 2854 (1995). Sampling procedures are guided by the UMTRA Project standard operating procedures (JEG, n.d.), the Technical Approach Document (DOE, 1989), and the most effective technical approach for the site. Additional site-specific documents relevant to the Mexican Hat site are the Mexican Hat Long-Term Surveillance Plan (currently in progress), and the Mexican Hat Site Observational Work Plan (currently in progress)

  9. HAT-P-38h

    DEFF Research Database (Denmark)

    Sato, Bun'ei; Hartman, Joel D.; Bakos, Gaspar Á.

    2012-01-01

    We report on the discovery of HAT-P-38b, a Saturn-mass exoplanet, transiting the V = 12.56 dwarf star GSC 2314-00559 on a P = 4.6404 d circular orbit. The host star is a 0.89 M-circle dot late G dwarf, with solar metallicity and a radius of 0.92 R-circle dot. The planetary companion has a mass of...

  10. A narrativa seriada televisiva: O seriado Mandrake produzido para a TV a cabo HBO

    Directory of Open Access Journals (Sweden)

    Lílian Fontes Moreira

    2007-10-01

    Full Text Available O presente artigo pretende abordar a investigação que se baseia na construção deum seriado produzido exclusivamente para uma TV a cabo, mais especificamente aHBO, baseado num personagem da literatura brasileira que surgiu na década de 60, opersonagem  Mandrake  criado pelo escritor Rubem Fonseca. Faremos, portanto, umtrajeto abordando a televisão como dispositivo audiovisual, seu papel na sociedadecontemporânea, as questões relativas à recepção e as características da narrativa seriadaaplicadas ao seriado em estudo.

  11. Home Automated Telemanagement (HAT System to Facilitate Self-Care of Patients with Chronic Diseases

    Directory of Open Access Journals (Sweden)

    Joseph Finkelstein

    2003-06-01

    Full Text Available Successful patient self-management requires a multidisciplinary approach that includes regular patient assessment, disease-specific education, control of medication adherence, implementation of health behavior change models and social support. Existing systems for computer-assisted disease management do not provide this multidisciplinary patient support and do not address treatment compliance issues. We developed the Home Automated Telemanagement (HAT system for patients with different chronic health conditions to facilitate their self-care. The HAT system consists of a home unit, HAT server, and clinician units. Patients at home use a palmtop or a laptop connected with a disease monitor on a regular basis. Each HAT session consists of self-testing, feedback, and educational components. The self-reported symptom data and objective results obtained from disease-specific sensors are automatically sent from patient homes to the HAT server in the hospital. Any web-enabled device can serve as a clinician unit to review patient results. The HAT system monitors self-testing results and patient compliance. The HAT system has been implemented and tested in patients receiving anticoagulation therapy, patients with asthma, COPD and other health conditions. Evaluation results indicated high level of acceptance of the HAT system by the patients and that the system has a positive impact on main clinical outcomes and patient satisfaction with medical care.

  12. Broad-band spectrophotometry of HAT-P-32 b

    DEFF Research Database (Denmark)

    Mallonn, M.; Bernt, I.; Herrero, E.

    2016-01-01

    Multicolour broad-band transit observations offer the opportunity to characterize the atmosphere of an extrasolar planet with small- to medium-sized telescopes. One of the most favourable targets is the hot Jupiter HAT-P-32 b. We combined 21 new transit observations of this planet with 36 previou...... makes a recent tentative detection of a scattering feature less likely. Instead, the available spectral measurements of HAT-P-32 b favour a completely flat spectrum from the near-UV to the near-IR. A plausible interpretation is a thick cloud cover at high altitudes....

  13. Probing the parameters of the HAT-P-2 system

    Science.gov (United States)

    Bailey, Elizabeth; Naoz, Smadar; Batygin, Konstantin

    2018-04-01

    The HAT-P-2 system contributes an exceptional set of parameters to the exoplanetary inventory. HAT-P-2b weighs in at approximately 9 Jupiter masses, residing on one of the most eccentric, close-in orbits of any hot Jupiter (e~0.5, a~0.07). The identification of an RV trend points to the existence of an additional, long-period companion, which may have facilitated Kozai-Lidov cycles in the system over its multi-Gyr history. The well-constrained parameters of HAT-P-2b present an opportunity to predict the parameters of the perturber, and furthermore, to assess the tidal dissipation involved in the system's evolution. In this work, we employ an octupole-level secular model to account for the interaction of the two massive planets, thus classifying the system's deviations away from purely quadrupolar dynamics.

  14. Crime, the Media, and Constructions of Reality: Using HBO's "The Wire" as a Frame of Reference

    Science.gov (United States)

    Guastaferro, Wendy P.

    2013-01-01

    This article shows how a uniquely situated television show was used as a pedagogical tool to address numerous criminal justice topics in a crime and media course. The show is Home Box Office's (HBO) "The Wire." The first season focused on "the law" and "the street" and how each is affected by drug enforcement,…

  15. The adipogenic acetyltransferase Tip60 targets activation function 1 of peroxisome proliferator-activated receptor gamma

    DEFF Research Database (Denmark)

    van Beekum, Olivier; Brenkman, Arjan B; Grøntved, Lars

    2008-01-01

    The transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) plays a key role in the regulation of lipid and glucose metabolism in adipocytes, by regulating their differentiation, maintenance, and function. The transcriptional activity of PPARgamma is dictated by the set...... in cells, and through use of chimeric proteins, we established that coactivation by Tip60 critically depends on the N-terminal activation function 1 of PPARgamma, a domain involved in isotype-specific gene expression and adipogenesis. Chromatin immunoprecipitation experiments showed that the endogenous Tip...... of proteins with which this nuclear receptor interacts under specific conditions. Here we identify the HIV-1 Tat-interacting protein 60 (Tip60) as a novel positive regulator of PPARgamma transcriptional activity. Using tandem mass spectrometry, we found that PPARgamma and the acetyltransferase Tip60 interact...

  16. Effect of increased yeast alcohol acetyltransferase activity on flavor profiles of wine and distillates.

    Science.gov (United States)

    Lilly, M; Lambrechts, M G; Pretorius, I S

    2000-02-01

    The distinctive flavor of wine, brandy, and other grape-derived alcoholic beverages is affected by many compounds, including esters produced during alcoholic fermentation. The characteristic fruity odors of the fermentation bouquet are primarily due to a mixture of hexyl acetate, ethyl caproate (apple-like aroma), iso-amyl acetate (banana-like aroma), ethyl caprylate (apple-like aroma), and 2-phenylethyl acetate (fruity, flowery flavor with a honey note). The objective of this study was to investigate the feasibility of improving the aroma of wine and distillates by overexpressing one of the endogenous yeast genes that controls acetate ester production during fermentation. The synthesis of acetate esters by the wine yeast Saccharomyces cerevisiae during fermentation is ascribed to at least three acetyltransferase activities, namely, alcohol acetyltransferase (AAT), ethanol acetyltransferase, and iso-amyl AAT. To investigate the effect of increased AAT activity on the sensory quality of Chenin blanc wines and distillates from Colombar base wines, we have overexpressed the alcohol acetyltransferase gene (ATF1) of S. cerevisiae. The ATF1 gene, located on chromosome XV, was cloned from a widely used commercial wine yeast strain of S. cerevisiae, VIN13, and placed under the control of the constitutive yeast phosphoglycerate kinase gene (PGK1) promoter and terminator. Chromoblot analysis confirmed the integration of the modified copy of ATF1 into the genome of three commercial wine yeast strains (VIN7, VIN13, and WE228). Northern blot analysis indicated constitutive expression of ATF1 at high levels in these yeast transformants. The levels of ethyl acetate, iso-amyl acetate, and 2-phenylethyl acetate increased 3- to 10-fold, 3.8- to 12-fold, and 2- to 10-fold, respectively, depending on the fermentation temperature, cultivar, and yeast strain used. The concentrations of ethyl caprate, ethyl caprylate, and hexyl acetate only showed minor changes, whereas the acetic acid

  17. A naturally-occurring histone acetyltransferase inhibitor derived from Garcinia indica impairs newly acquired and reactivated fear memories.

    Directory of Open Access Journals (Sweden)

    Stephanie A Maddox

    Full Text Available The study of the cellular and molecular mechanisms underlying the consolidation and reconsolidation of traumatic fear memories has progressed rapidly in recent years, yet few compounds have emerged that are readily useful in a clinical setting for the treatment of anxiety disorders such as post-traumatic stress disorder (PTSD. Here, we use a combination of biochemical, behavioral, and neurophysiological methods to systematically investigate the ability of garcinol, a naturally-occurring histone acetyltransferase (HAT inhibitor derived from the rind of the fruit of the Kokum tree (Garcina indica, to disrupt the consolidation and reconsolidation of Pavlovian fear conditioning, a widely studied rodent model of PTSD. We show that local infusion of garcinol into the rat lateral amygdala (LA impairs the training and retrieval-related acetylation of histone H3 in the LA. Further, we show that either intra-LA or systemic administration of garcinol within a narrow window after either fear conditioning or fear memory retrieval significantly impairs the consolidation and reconsolidation of a Pavlovian fear memory and associated neural plasticity in the LA. Our findings suggest that a naturally-occurring compound derived from the diet that regulates chromatin function may be useful in the treatment of newly acquired or recently reactivated traumatic memories.

  18. A Naturally-Occurring Histone Acetyltransferase Inhibitor Derived from Garcinia indica Impairs Newly Acquired and Reactivated Fear Memories

    Science.gov (United States)

    Maddox, Stephanie A.; Watts, Casey S.; Doyère, Valérie; Schafe, Glenn E.

    2013-01-01

    The study of the cellular and molecular mechanisms underlying the consolidation and reconsolidation of traumatic fear memories has progressed rapidly in recent years, yet few compounds have emerged that are readily useful in a clinical setting for the treatment of anxiety disorders such as post-traumatic stress disorder (PTSD). Here, we use a combination of biochemical, behavioral, and neurophysiological methods to systematically investigate the ability of garcinol, a naturally-occurring histone acetyltransferase (HAT) inhibitor derived from the rind of the fruit of the Kokum tree (Garcina indica), to disrupt the consolidation and reconsolidation of Pavlovian fear conditioning, a widely studied rodent model of PTSD. We show that local infusion of garcinol into the rat lateral amygdala (LA) impairs the training and retrieval-related acetylation of histone H3 in the LA. Further, we show that either intra-LA or systemic administration of garcinol within a narrow window after either fear conditioning or fear memory retrieval significantly impairs the consolidation and reconsolidation of a Pavlovian fear memory and associated neural plasticity in the LA. Our findings suggest that a naturally-occurring compound derived from the diet that regulates chromatin function may be useful in the treatment of newly acquired or recently reactivated traumatic memories. PMID:23349897

  19. Giant Paperclip Necklaces, Soup-Can Rings and Cherry-Pie Hats

    Science.gov (United States)

    Winters, Laurel A.

    2011-01-01

    In this article, the author describes an art project inspired by the wearable sculpture art created by artist Marjorie Schick. Students used wallpaper paste and newspapers to create papier-mache for a mountain hat, a cherry-pie mask/hat, a "dress" shoe and a Cubistic mask. Cardboard was used in many of these things, in addition to being used as…

  20. Detection of the Secondary Eclipse of Exoplanet HAT P-11b

    Science.gov (United States)

    Barry, R. K.; Deming, L. D.; Bakos, G.; Harrington, J.; Madhusudhan, N.; Noyes, R.; Seager, S.

    2010-01-01

    We have successfully conducted secondary eclipse observations of exoplanet HAT-P-11b using the Spitzer Space Telescope. HAT-P-11b was, until very recently, the smallest transiting extrasolar planet yet found and one of only two known exo-Neptunes. We observed the system at 3.6 microns for a period of 22 hours centered on the anticipated secondary eclipse time, to detect the eclipse and determine its phase. Having detected the secondary eclipse, we are at present making a more focused series of observations in both the 3.6 and 4.5 micron bands to fully characterize it. HAT-P-11b has a period of 4.8878 days, radius of 0.422 RJ, mass of 0.081 MJ and semi-major axis 0.053 AU. Measurements of the secondary eclipse will serve to clarify two key issues; 1) the planetary brightness temperature and the nature of its atmosphere, and 2) the eccentricity of its orbit, with implications for its dynamical evolution. A precise determination of the orbit phase for the secondary eclipse will also be of great utility for Kepler observations of this system at visible wavelengths.

  1. Mechanism of the lysosomal membrane enzyme acetyl coenzyme A: alpha-glucosaminide N-acetyltransferase

    International Nuclear Information System (INIS)

    Bame, K.J.

    1986-01-01

    Acetyl-CoA:α-glucosaminide N-acetyltransferase is a lysosomal membrane enzyme, deficient in the genetic disease Sanfilippo C syndrome. The enzyme catalyzes the transfer of an acetyl group from cytoplasmic acetyl-CoA to terminal α-glucosamine residues of heparan sulfate within the organelle. The reaction mechanism was examined using high purified lysosomal membranes from rat liver and human fibroblasts. The N-acetyltransferase reaction is optimal above pH 5.5 and a 2-3 fold stimulation of activity is observed in the presence of 0.1% taurodeoxycholate. Double reciprocal analysis and product inhibition studies indicate that the enzyme works by a Di-Iso Ping Pong Bi Bi mechanism. The binding of acetyl-CoA to the enzyme is measured by exchange label from [ 3 H]CoA to acetyl-CoA, and is optimal at pH's above 7.0. The acetyl-enzyme intermediate is formed by incubating membranes with [ 3 H]acetyl-CoA. The acetyl group can be transferred to glucosamine, forming [ 3 H]N-acetylglucosamine; the transfer is optimal between pH 4 and 5. Lysosomal membranes from Sanfilippo C fibroblasts confirm that these half reactions carried out by the N-acetyltransferase. The enzyme is inactivated by N-bromosuccinimide and diethylpyrocarbonate, indicating that a histidine is involved in the reaction. These results suggest that the histidine residue is at the active site of the enzyme. The properties of the N-acetyltransferase in the membrane, the characterization of the enzyme kinetics, the chemistry of a histidine mediated acetylation and the pH difference across the lysosomal membrane all support a transmembrane acetylation mechanism

  2. Characterization of the atmosphere of the hot Jupiter HAT-P-32Ab and the M-dwarf companion HAT-P-32B

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Ming; Wright, Jason T.; Curtis, Jason [Department of Astronomy and Astrophysics, Pennsylvania State University, PA 16802 (United States); O' Rourke, Joseph G.; Knutson, Heather A.; Ngo, Henry [Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125 (United States); Burrows, Adam [Department of Astrophysical Sciences, Princeton University, 4 Ivy Lane, Princeton, NJ 08544 (United States); Fortney, Johnathan [Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States); Fulton, Benjamin J.; Baranec, Christoph [Institute for Astronomy, University of Hawai' i at Mānoa, Hilo, HI 96720-2700 (United States); Riddle, Reed; Hinkley, Sasha [Division of Physics, Mathematics, and Astronomy, California Institute of Technology, Pasadena, CA 91125 (United States); Law, Nicholas M. [Department of Physics and Astronomy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3255 (United States); Muirhead, Philip S. [Department of Astronomy, Boston University, 725 Commonwealth Avenue, Boston, MA 02215 (United States); Showman, Adam P. [Department of Planetary Sciences and Lunar and Planetary Laboratory, The University of Arizona, Tucson, AZ 85721 (United States); Burruss, Rick, E-mail: mingzhao@psu.edu [Jet Propulsion Laboratory, California Institute of Technology, CA 91109 (United States)

    2014-12-01

    We report secondary eclipse photometry of the hot Jupiter HAT-P-32Ab, taken with Hale/Wide-field Infra-Red Camera (WIRC) in H and K{sub S} bands and with Spitzer/IRAC at 3.6 and 4.5 μm. We carried out adaptive optics imaging of the planet host star HAT-P-32A and its companion HAT-P-32B in the near-IR and the visible. We clearly resolve the two stars from each other and find a separation of 2.''923 ± 0.''004 and a position angle 110.°64 ± 0.°12. We measure the flux ratios of the binary in g'r'i'z' and H and K{sub S} bands, and determine T {sub eff}= 3565 ± 82 K for the companion star, corresponding to an M1.5 dwarf. We use PHOENIX stellar atmosphere models to correct the dilution of the secondary eclipse depths of the hot Jupiter due to the presence of the M1.5 companion. We also improve the secondary eclipse photometry by accounting for the non-classical, flux-dependent nonlinearity of the WIRC IR detector in the H band. We measure planet-to-star flux ratios of 0.090% ± 0.033%, 0.178% ± 0.057%, 0.364% ± 0.016%, and 0.438% ± 0.020% in the H, K{sub S} , 3.6 and 4.5 μm bands, respectively. We compare these with planetary atmospheric models, and find they prefer an atmosphere with a temperature inversion and inefficient heat redistribution. However, we also find that the data are equally well described by a blackbody model for the planet with T {sub p} = 2042 ± 50 K. Finally, we measure a secondary eclipse timing offset of 0.3 ± 1.3 minutes from the predicted mid-eclipse time, which constrains e = 0.0072{sub −0.0064}{sup +0.0700} when combined with radial velocity data and is more consistent with a circular orbit.

  3. New N-Acetyltransferase Fold in the Structure and Mechanism of the Phosphonate Biosynthetic Enzyme FrbF

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Brian; Cobb, Ryan E.; DeSieno, Matthew A.; Zhao, Huimin; Nair, Satish K. (UIUC)

    2015-10-15

    The enzyme FrbF from Streptomyces rubellomurinus has attracted significant attention due to its role in the biosynthesis of the antimalarial phosphonate FR-900098. The enzyme catalyzes acetyl transfer onto the hydroxamate of the FR-900098 precursors cytidine 5'-monophosphate-3-aminopropylphosphonate and cytidine 5'-monophosphate-N-hydroxy-3-aminopropylphosphonate. Despite the established function as a bona fide N-acetyltransferase, FrbF shows no sequence similarity to any member of the GCN5-like N-acetyltransferase (GNAT) superfamily. Here, we present the 2.0 {angstrom} resolution crystal structure of FrbF in complex with acetyl-CoA, which demonstrates a unique architecture that is distinct from those of canonical GNAT-like acetyltransferases. We also utilized the co-crystal structure to guide structure-function studies that identified the roles of putative active site residues in the acetyltransferase mechanism. The combined biochemical and structural analyses of FrbF provide insights into this previously uncharacterized family of N-acetyltransferases and also provide a molecular framework toward the production of novel N-acyl derivatives of FR-900098.

  4. Maximizing prosthetic valve size with the Top Hat supra-annular aortic valve

    DEFF Research Database (Denmark)

    Aagaard, Jan; Geha, Alexander S.

    2007-01-01

    BACKGROUND AND AIM OF THE STUDY: The CarboMedics Top Hat supra-annular aortic valve allows a one-size (and often two-size) increase over the standard intra-annular valve. This advantage should minimize the risk of patient-prosthesis mismatch, where the effective prosthetic valve orifice area....... This study evaluates the authors' clinical experience with Top Hat supra-annular aortic valve size selection, and the technical aspects of implantation. METHODS: Between January 1999 and October 2005, a total of 251 consecutive patients underwent 252 aortic valve replacements with Top Hat supra...... required unplanned coronary bypass, and 30-day mortality was 2.0% (5/251), indicating a good safety profile for the valves implanted in this series. CONCLUSION: The general distribution of implant sizes in the US indicates that cardiac surgeons may be under-sizing the Top Hat supra-annular aortic valve...

  5. Application of Human-Autonomy Teaming (HAT) Patterns to Reduced Crew Operations (RCO)

    Science.gov (United States)

    Shively, R. Jay; Brandt, Summer L.; Lachter, Joel; Matessa, Mike; Sadler, Garrett; Battiste, Henri

    2016-01-01

    As part of the Air Force - NASA Bi-Annual Research Council Meeting, slides will be presented on recent Reduced Crew Operations (RCO) work. Unmanned aerial systems, robotics, advanced cockpits, and air traffic management are all examples of domains that are seeing dramatic increases in automation. While automation may take on some tasks previously performed by humans, humans will still be required, for the foreseeable future, to remain in the system. The collaboration with humans and these increasingly autonomous systems will begin to resemble cooperation between teammates, rather than simple task allocation. It is critical to understand this human-autonomy teaming (HAT) to optimize these systems in the future. One methodology to understand HAT is by identifying recurring patterns of HAT that have similar characteristics and solutions. A methodology for identifying HAT patterns to an advanced cockpit project is discussed.

  6. Mutation of the CH1 Domain in the Histone Acetyltransferase CREBBP Results in Autism-Relevant Behaviors in Mice.

    Directory of Open Access Journals (Sweden)

    Fei Zheng

    Full Text Available Autism spectrum disorders (ASDs are a group of neurodevelopmental afflictions characterized by repetitive behaviors, deficits in social interaction, and impaired communication skills. For most ASD patients, the underlying causes are unknown. Genetic mutations have been identified in about 25 percent of ASD cases, including mutations in epigenetic regulators, suggesting that dysregulated chromatin or DNA function is a critical component of ASD. Mutations in the histone acetyltransferase CREB binding protein (CBP, CREBBP cause Rubinstein-Taybi Syndrome (RTS, a developmental disorder that includes ASD-like symptoms. Recently, genomic studies involving large numbers of ASD patient families have theoretically modeled CBP and its paralog p300 (EP300 as critical hubs in ASD-associated protein and gene interaction networks, and have identified de novo missense mutations in highly conserved residues of the CBP acetyltransferase and CH1 domains. Here we provide animal model evidence that supports this notion that CBP and its CH1 domain are relevant to autism. We show that mice with a deletion mutation in the CBP CH1 (TAZ1 domain (CBPΔCH1/ΔCH1 have an RTS-like phenotype that includes ASD-relevant repetitive behaviors, hyperactivity, social interaction deficits, motor dysfunction, impaired recognition memory, and abnormal synaptic plasticity. Our results therefore indicate that loss of CBP CH1 domain function contributes to RTS, and possibly ASD, and that this domain plays an essential role in normal motor function, cognition and social behavior. Although the key physiological functions affected by ASD-associated mutation of epigenetic regulators have been enigmatic, our findings are consistent with theoretical models involving CBP and p300 in ASD, and with a causative role for recently described ASD-associated CBP mutations.

  7. Radiologic characterization of the Mexican Hat, Utah, uranium mill tailings remedial action site: Appendix D, Addenda D1--D7

    Energy Technology Data Exchange (ETDEWEB)

    Ludlam, J.R.

    1985-01-01

    This radiologic characterization of the inactive uranium millsite at Mexican Hat, Utah, was conducted by Bendix Field Engineering Corporation foe the US Department of Energy (DOE), Grand Junction Project Office, in response to and in accord with a Statement of Work prepared by the DOE Uranium Mill tailings Remedial Action Project (UMTRAP) Technical Assistance Contractor, Jacobs Engineering Group, Inc. the objective of this project was to determine the horizontal and vertical extent of contamination that exceeds the US Environmental Protection Agency (EPA) standards at the Mexican Hat site. The data presented in this report are required for characterization of the areas adjacent to the Mexican Hat tailings piles and for the subsequent design of cleanup activities. Some on-pile sampling was required to determine the depth of the 15-pCi/g Ra-226 interface in an area where wind and water erosion has taken place.

  8. Estimating q-hat in Quenched Lattice SU(2) Gauge Theory

    International Nuclear Information System (INIS)

    Majumder, Abhijit

    2013-01-01

    The propagation of a virtual quark in a thermal medium is considered. The non-perturbative jet transport coefficient q -hat is estimated in quark less SU(2) lattice gauge theory. The light like correlator which defines q -hat , defined in the regime where the jet has small virtuality compared to its energy, is analytically related to a series of local operators in the deep Euclidean region, where the jet's virtuality is of the same order as its energy. It is demonstrated that in this region, for temperatures in the range of T=400–600 MeV, and for jet energies above 20 GeV, the leading term in the series is dominant over the next-to-leading term and thus yields an estimate of the value of q -hat . In these proceedings we discuss the details of the numerical calculation

  9. HAT-P-13b,c: A TRANSITING HOT JUPITER WITH A MASSIVE OUTER COMPANION ON AN ECCENTRIC ORBIT

    International Nuclear Information System (INIS)

    Bakos, G. A.; Noyes, R. W.; Hartman, J.; Torres, G.; Latham, D. W.; Sasselov, D. D.; Stefanik, R. P.; Sipocz, B.; Kovacs, Gabor; Esquerdo, G. A.; Pal, A.; Howard, A. W.; Marcy, G. W.; Kovacs, Geza; Fischer, D. A.; Johnson, J. A.; Lazar, J.; Papp, I.; Sari, P.

    2009-01-01

    We report on the discovery of a planetary system with a close-in transiting hot Jupiter on a near circular orbit and a massive outer planet on a highly eccentric orbit. The inner planet, HAT-P-13b, transits the bright V = 10.622 G4 dwarf star GSC 3416 - 00543 every P = 2.916260 ± 0.000010 days, with transit epoch T c = 2454779.92979 ± 0.00038 (BJD) and duration 0.1345 ± 0.0017 days. The outer planet HAT-P-13c orbits the star every P 2 = 428.5 ± 3.0 days with a nominal transit center (assuming zero impact parameter) of T 2c = 2454870.4 ± 1.8 (BJD) or time of periastron passage T 2,peri = 2454890.05 ± 0.48 (BJD). Transits of the outer planet have not been observed, and may not be present. The host star has a mass of 1.22 +0.05 -0.10 M sun , radius of 1.56 ± 0.08 R sun , effective temperature of 5653 ± 90 K, and is rather metal-rich with [Fe/H] = +0.41 ± 0.08. The inner planetary companion has a mass of 0.853 +0.029 -0.046 M J , and radius of 1.281 ± 0.079 R J , yielding a mean density of 0.498 +0.103 -0.069 g cm -3 . The outer companion has m 2 sin i 2 = 15.2 ± 1.0 M J , and orbits on a highly eccentric orbit of e 2 = 0.691 ± 0.018. While we have not detected significant transit timing variations of HAT-P-13b, due to gravitational and light-travel time effects, future observations will constrain the orbital inclination of HAT-P-13c, along with its mutual inclination to HAT-P-13b. The HAT-P-13 (b, c) double-planet system may prove extremely valuable for theoretical studies of the formation and dynamics of planetary systems.

  10. USING SIX THINKING HATS AS A TOOL FOR LATERAL THINKING IN ORGANIZATIONAL PROBLEM SOLVING

    OpenAIRE

    Dr. P. S. Aithal; Dr. P. M. Suresh Kumar

    2016-01-01

    Six thinking hats is recently introduced technique which outlines different thinking styles required by an individual while analysing a given problem in an effective way. The technique correlates different thinking styles used in a systematic problem-solving procedure with different coloured hats. Alternately, by conceptualizing each type of hat, the person focuses on the style of thinking associated with each colour so that the problem can be analysed from different angles and frame of refer...

  11. The elliptic quantum algebra U{sub q,p}(sl-hat{sub N}) and its vertex operators

    Energy Technology Data Exchange (ETDEWEB)

    Chang Wenjing [School of Mathematical Science, Capital Normal University, Beijing 100048 (China); Ding Xiangmao [Institute of Applied Mathematics, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing 100190 (China)], E-mail: wjchang@amss.ac.cn, E-mail: xmding@amss.ac.cn

    2009-10-23

    We construct a realization of the elliptic quantum algebra U{sub q,p}(sl-hat{sub N}) for any given level k in terms of free boson fields and their twisted partners. It can be considered as the elliptic deformation of the Wakimoto realization of the quantum affine algebra U{sub q}(sl-hat{sub N}). We also construct a family of screening currents, which commute with the currents of U{sub q,p}(sl-hat{sub N}) up to total q-differences. And we give explicit twisted expressions for the type I and type II vertex operators of U{sub q,p}(sl-hat{sub N}) by twisting the known results of the type I vertex operators of the quantum affine algebra U{sub q}(sl-hat{sub N}) and the new results of the type II vertex operators of U{sub q}(sl-hat{sub N}) we obtained in this paper.

  12. Remedial Action Plan for the codisposal and stabilization of the Monument Valley and Mexican Hat uranium mill tailings at Mexican Hat, Utah

    International Nuclear Information System (INIS)

    1993-02-01

    This document is a revision of the original Mexiacan Hat Remedial Action Plan (RAP) and RAP Modification submitted in July 1988 and January 1989, respectively, along with updated design documents. This RAP has been developed to serve a two-fold purpose. It presents the activities proposed by the Department of Energy (DOE) to accomplish long-term stabilization and control of the residual radioactive materials (RRM) from Monument Valley, Arizona, and Mexican Hat, Utah, at the Mexican Hat disposal site. It also serves to document the concurrence of both the Navajo Nation and the Nuclear Regulatory Commission (NRC) in the remedial action. This agreement, upon execution by DOE and the Navajo Nation and concurrence by the NRC, becomes Appendix B of the Cooperative Agreement. This document has been structured to provide a comprehensive understanding of the remedial action proposed for the Monument Valley and Mexican Hat sites. It includes specific design and construction requirements for the remedial action. Pertinent information and data are included with reference given to the supporting documents. Section 2.0 presents the EPA standards, including a discussion of their objectives. Section 3. 0 summarizes the present site characteristics and provides a definition of site-specific problems. Section 4.0 is the site design for the proposed action. Section 5.0 presents the water resources protection strategy. Section 6.0 summarizes the plan for ensuring health and safety protection for the surrounding community and the on- site workers. Section 7.0 lists the responsibilities of the project participants. Section 8.0 describes the features of the long-term surveillance and maintenance plan

  13. iHAT: interactive Hierarchical Aggregation Table for Genetic Association Data

    Directory of Open Access Journals (Sweden)

    Heinrich Julian

    2012-05-01

    Full Text Available Abstract In the search for single-nucleotide polymorphisms which influence the observable phenotype, genome wide association studies have become an important technique for the identification of associations between genotype and phenotype of a diverse set of sequence-based data. We present a methodology for the visual assessment of single-nucleotide polymorphisms using interactive hierarchical aggregation techniques combined with methods known from traditional sequence browsers and cluster heatmaps. Our tool, the interactive Hierarchical Aggregation Table (iHAT, facilitates the visualization of multiple sequence alignments, associated metadata, and hierarchical clusterings. Different color maps and aggregation strategies as well as filtering options support the user in finding correlations between sequences and metadata. Similar to other visualizations such as parallel coordinates or heatmaps, iHAT relies on the human pattern-recognition ability for spotting patterns that might indicate correlation or anticorrelation. We demonstrate iHAT using artificial and real-world datasets for DNA and protein association studies as well as expression Quantitative Trait Locus data.

  14. WASP-12b AND HAT-P-8b are members of triple star systems

    Energy Technology Data Exchange (ETDEWEB)

    Bechter, Eric B.; Crepp, Justin R.; Matthews, Christopher T. [Department of Physics, University of Notre Dame, 225 Nieuwland Science Hall, Notre Dame, IN 46556 (United States); Ngo, Henry; Knutson, Heather A.; Batygin, Konstantin; Johnson, John Asher [Department of Planetary Science, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125 (United States); Hinkley, Sasha; Muirhead, Philip S.; Montet, Benjamin T.; Morton, Timothy D. [Department of Astronomy, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125 (United States); Howard, Andrew W., E-mail: ebechter@nd.edu [Institute for Astronomy, University of Hawaii, 2680 Woodlawn Drive, Honolulu, HI 96822 (United States)

    2014-06-10

    We present high spatial resolution images that demonstrate that WASP-12b and HAT-P-8b orbit the primary stars of hierarchical triple star systems. In each case, two distant companions with colors and brightnesses consistent with M dwarfs co-orbit the hot Jupiter planet host as well as one another. Our adaptive optics images spatially resolve the secondary around WASP-12, previously identified by Bergfors et al. and Crossfield et al. into two distinct sources separated by 84.3 ± 0.6 mas (21 ± 3 AU). We find that the secondary to HAT-P-8, also identified by Bergfors et al., is in fact composed of two stars separated by 65.3 ± 0.5 mas (15 ± 1 AU). Our follow-up observations demonstrate physical association through common proper motion. HAT-P-8 C has a particularly low mass, which we estimate to be 0.18 ± 0.02 M {sub ☉} using photometry. Due to their hierarchy, WASP-12 BC and HAT-P-8 BC will enable the first dynamical mass determination for hot Jupiter stellar companions. These previously well studied planet hosts now represent higher-order multi-star systems with potentially complex dynamics, underscoring the importance of diffraction-limited imaging and providing additional context for understanding the migrant population of transiting hot Jupiters.

  15. WASP-12b and HAT-P-8b are Members of Triple Star Systems

    Science.gov (United States)

    Bechter, Eric B.; Crepp, Justin R.; Ngo, Henry; Knutson, Heather A.; Batygin, Konstantin; Hinkley, Sasha; Muirhead, Philip S.; Johnson, John Asher; Howard, Andrew W.; Montet, Benjamin T.; Matthews, Christopher T.; Morton, Timothy D.

    2014-06-01

    We present high spatial resolution images that demonstrate that WASP-12b and HAT-P-8b orbit the primary stars of hierarchical triple star systems. In each case, two distant companions with colors and brightnesses consistent with M dwarfs co-orbit the hot Jupiter planet host as well as one another. Our adaptive optics images spatially resolve the secondary around WASP-12, previously identified by Bergfors et al. and Crossfield et al. into two distinct sources separated by 84.3 ± 0.6 mas (21 ± 3 AU). We find that the secondary to HAT-P-8, also identified by Bergfors et al., is in fact composed of two stars separated by 65.3 ± 0.5 mas (15 ± 1 AU). Our follow-up observations demonstrate physical association through common proper motion. HAT-P-8 C has a particularly low mass, which we estimate to be 0.18 ± 0.02 M ⊙ using photometry. Due to their hierarchy, WASP-12 BC and HAT-P-8 BC will enable the first dynamical mass determination for hot Jupiter stellar companions. These previously well studied planet hosts now represent higher-order multi-star systems with potentially complex dynamics, underscoring the importance of diffraction-limited imaging and providing additional context for understanding the migrant population of transiting hot Jupiters.

  16. WASP-12b AND HAT-P-8b are members of triple star systems

    International Nuclear Information System (INIS)

    Bechter, Eric B.; Crepp, Justin R.; Matthews, Christopher T.; Ngo, Henry; Knutson, Heather A.; Batygin, Konstantin; Johnson, John Asher; Hinkley, Sasha; Muirhead, Philip S.; Montet, Benjamin T.; Morton, Timothy D.; Howard, Andrew W.

    2014-01-01

    We present high spatial resolution images that demonstrate that WASP-12b and HAT-P-8b orbit the primary stars of hierarchical triple star systems. In each case, two distant companions with colors and brightnesses consistent with M dwarfs co-orbit the hot Jupiter planet host as well as one another. Our adaptive optics images spatially resolve the secondary around WASP-12, previously identified by Bergfors et al. and Crossfield et al. into two distinct sources separated by 84.3 ± 0.6 mas (21 ± 3 AU). We find that the secondary to HAT-P-8, also identified by Bergfors et al., is in fact composed of two stars separated by 65.3 ± 0.5 mas (15 ± 1 AU). Our follow-up observations demonstrate physical association through common proper motion. HAT-P-8 C has a particularly low mass, which we estimate to be 0.18 ± 0.02 M ☉ using photometry. Due to their hierarchy, WASP-12 BC and HAT-P-8 BC will enable the first dynamical mass determination for hot Jupiter stellar companions. These previously well studied planet hosts now represent higher-order multi-star systems with potentially complex dynamics, underscoring the importance of diffraction-limited imaging and providing additional context for understanding the migrant population of transiting hot Jupiters.

  17. The nonstructural protein NP1 of human bocavirus 1 induces cell cycle arrest and apoptosis in Hela cells

    International Nuclear Information System (INIS)

    Sun, Bin; Cai, Yingyue; Li, Yongshu; Li, Jingjing; Liu, Kaiyu; Li, Yi; Yang, Yongbo

    2013-01-01

    Human bocavirus type 1 (HBoV1) is a newly identified pathogen associated with human respiratory tract illnesses. Previous studies demonstrated that proteins of HBoV1 failed to cause cell death, which is considered as a possible common feature of bocaviruses. However, our work showed that the NP1 of HBoV1 induced apoptotic cell death in Hela cells in the absence of viral genome replication and expression of other viral proteins. Mitochondria apoptotic pathway was involved in the NP1-induced apoptosis that was confirmed by apoptotic characteristics including morphological changes, DNA fragmentation and caspase activation. We also demonstrated that the cell cycle of NP1-transfected Hela cells was transiently arrested at G2/M phase followed by rapid appearance of apoptosis and that the N terminal domain of NP1 was critical to its nuclear localization and function in apoptosis induction in Hela cells. These findings might provide alternative information for further study of mechanism of HBoV1 pathogenesis. - Highlights: ► NP1 protein of HBoV1 induced apoptosis in Hela cells was first reported. ► NP1 induced-apoptosis followed the cell cycle arrest at G2/M phase. ► The NP1 induced-apoptosis was mediated by mitochondrion apoptotic pathway. ► N terminal of NP1 was critical for apoptosis induction and nuclear localization

  18. The nonstructural protein NP1 of human bocavirus 1 induces cell cycle arrest and apoptosis in Hela cells

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Bin; Cai, Yingyue; Li, Yongshu [College of Life Science, Central China Normal University, Wuhan 430079, Hubei (China); Li, Jingjing [College of Life Science, Hubei Normal University, Huangshi 435002, Hubei (China); Liu, Kaiyu [College of Life Science, Central China Normal University, Wuhan 430079, Hubei (China); Li, Yi, E-mail: johnli2668@hotmail.com [College of Life Science, Central China Normal University, Wuhan 430079, Hubei (China); Bioengineering Department, Wuhan Bioengineering Institute, Wuhan 430415, Hubei (China); Yang, Yongbo, E-mail: yongboyang@mail.ccnu.edu.cn [College of Life Science, Central China Normal University, Wuhan 430079, Hubei (China)

    2013-05-25

    Human bocavirus type 1 (HBoV1) is a newly identified pathogen associated with human respiratory tract illnesses. Previous studies demonstrated that proteins of HBoV1 failed to cause cell death, which is considered as a possible common feature of bocaviruses. However, our work showed that the NP1 of HBoV1 induced apoptotic cell death in Hela cells in the absence of viral genome replication and expression of other viral proteins. Mitochondria apoptotic pathway was involved in the NP1-induced apoptosis that was confirmed by apoptotic characteristics including morphological changes, DNA fragmentation and caspase activation. We also demonstrated that the cell cycle of NP1-transfected Hela cells was transiently arrested at G2/M phase followed by rapid appearance of apoptosis and that the N terminal domain of NP1 was critical to its nuclear localization and function in apoptosis induction in Hela cells. These findings might provide alternative information for further study of mechanism of HBoV1 pathogenesis. - Highlights: ► NP1 protein of HBoV1 induced apoptosis in Hela cells was first reported. ► NP1 induced-apoptosis followed the cell cycle arrest at G2/M phase. ► The NP1 induced-apoptosis was mediated by mitochondrion apoptotic pathway. ► N terminal of NP1 was critical for apoptosis induction and nuclear localization.

  19. Bi-Directional Communication: A Critical Component of HAT

    Science.gov (United States)

    Shively, Robert J.

    2016-01-01

    Known problems with automation include lack of mode awareness, automation brittleness, and risk of miscalibrated trust. Human-Autonomy Teaming (HAT) is essential for improving these problems. This presentation outlines critical components for Human-Autonomy Teaming.

  20. CPLA 1.0: an integrated database of protein lysine acetylation.

    Science.gov (United States)

    Liu, Zexian; Cao, Jun; Gao, Xinjiao; Zhou, Yanhong; Wen, Longping; Yang, Xiangjiao; Yao, Xuebiao; Ren, Jian; Xue, Yu

    2011-01-01

    As a reversible post-translational modification (PTM) discovered decades ago, protein lysine acetylation was known for its regulation of transcription through the modification of histones. Recent studies discovered that lysine acetylation targets broad substrates and especially plays an essential role in cellular metabolic regulation. Although acetylation is comparable with other major PTMs such as phosphorylation, an integrated resource still remains to be developed. In this work, we presented the compendium of protein lysine acetylation (CPLA) database for lysine acetylated substrates with their sites. From the scientific literature, we manually collected 7151 experimentally identified acetylation sites in 3311 targets. We statistically studied the regulatory roles of lysine acetylation by analyzing the Gene Ontology (GO) and InterPro annotations. Combined with protein-protein interaction information, we systematically discovered a potential human lysine acetylation network (HLAN) among histone acetyltransferases (HATs), substrates and histone deacetylases (HDACs). In particular, there are 1862 triplet relationships of HAT-substrate-HDAC retrieved from the HLAN, at least 13 of which were previously experimentally verified. The online services of CPLA database was implemented in PHP + MySQL + JavaScript, while the local packages were developed in JAVA 1.5 (J2SE 5.0). The CPLA database is freely available for all users at: http://cpla.biocuckoo.org.

  1. Planet-induced Stellar Pulsations in HAT-P-2's Eccentric System

    International Nuclear Information System (INIS)

    Wit, Julien de; Lewis, Nikole K.; Knutson, Heather A.; Batygin, Konstantin; Fuller, Jim; Antoci, Victoria; Fulton, Benjamin J.; Laughlin, Gregory; Deming, Drake; Shporer, Avi; Cowan, Nicolas B.; Agol, Eric; Burrows, Adam S.; Fortney, Jonathan J.; Langton, Jonathan; Showman, Adam P.

    2017-01-01

    Extrasolar planets on eccentric short-period orbits provide a laboratory in which to study radiative and tidal interactions between a planet and its host star under extreme forcing conditions. Studying such systems probes how the planet’s atmosphere redistributes the time-varying heat flux from its host and how the host star responds to transient tidal distortion. Here, we report the insights into the planet–star interactions in HAT-P-2's eccentric planetary system gained from the analysis of ∼350 hr of 4.5 μ m observations with the Spitzer Space Telescope . The observations show no sign of orbit-to-orbit variability nor of orbital evolution of the eccentric planetary companion, HAT-P-2 b. The extensive coverage allows us to better differentiate instrumental systematics from the transient heating of HAT-P-2 b’s 4.5 μ m photosphere and yields the detection of stellar pulsations with an amplitude of approximately 40 ppm. These pulsation modes correspond to exact harmonics of the planet’s orbital frequency, indicative of a tidal origin. Transient tidal effects can excite pulsation modes in the envelope of a star, but, to date, such pulsations had only been detected in highly eccentric stellar binaries. Current stellar models are unable to reproduce HAT-P-2's pulsations, suggesting that our understanding of the interactions at play in this system is incomplete.

  2. Diversification of the Histone Acetyltransferase GCN5 through Alternative Splicing in Brachypodium distachyon

    Directory of Open Access Journals (Sweden)

    Alexandre Martel

    2017-12-01

    Full Text Available The epigenetic modulatory SAGA complex is involved in various developmental and stress responsive pathways in plants. Alternative transcripts of the SAGA complex's enzymatic subunit GCN5 have been identified in Brachypodium distachyon. These splice variants differ based on the presence and integrity of their conserved domain sequences: the histone acetyltransferase domain, responsible for catalytic activity, and the bromodomain, involved in acetyl-lysine binding and genomic loci targeting. GCN5 is the wild-type transcript, while alternative splice sites result in the following transcriptional variants: L-GCN5, which is missing the bromodomain and S-GCN5, which lacks the bromodomain as well as certain motifs of the histone acetyltransferase domain. Absolute mRNA quantification revealed that, across eight B. distachyon accessions, GCN5 was the dominant transcript isoform, accounting for up to 90% of the entire transcript pool, followed by L-GCN5 and S-GCN5. A cycloheximide treatment further revealed that the S-GCN5 splice variant was degraded through the nonsense-mediated decay pathway. All alternative BdGCN5 transcripts displayed similar transcript profiles, being induced during early exposure to heat and displaying higher levels of accumulation in the crown, compared to aerial tissues. All predicted protein isoforms localize to the nucleus, which lends weight to their purported epigenetic functions. S-GCN5 was incapable of forming an in vivo protein interaction with ADA2, the transcriptional adaptor that links the histone acetyltransferase subunit to the SAGA complex, while both GCN5 and L-GCN5 interacted with ADA2, which suggests that a complete histone acetyltransferase domain is required for BdGCN5-BdADA2 interaction in vivo. Thus, there has been a diversification in BdGCN5 through alternative splicing that has resulted in differences in conserved domain composition, transcript fate and in vivo protein interaction partners. Furthermore, our

  3. Long-term surveillance plan for the Mexican Hat disposal site, Mexican Hat, Utah

    International Nuclear Information System (INIS)

    1996-01-01

    This plan describes the long-term surveillance activities for the Uranium Mill Tailings Remedial Action (UMTRA) Project disposal site at Mexican Hat, Utah. The US Department of Energy (DOE) will carry out these activities to ensure that the disposal site continues to function as designed. This long-term surveillance plan (LTSP) was prepared as a requirement for acceptance under the US Nuclear Regulatory Commission (NRC) general license for custody and long-term care of residual radioactive material (RRM). This LTSPC documents the land ownership interests and details how the long-term care of the disposal site will be accomplished

  4. Presence of Human Bocavirus 1 in Hospitalised Children with Acute Respiratory Tract Infections in Latvia and Lithuania / Cilvēka Bokavīrusa 1 Klātbūtne Latvijā Un Lietuvā Hospitalizētiem Bērniem Ar Akūtām Elpceīu Slimībām

    Directory of Open Access Journals (Sweden)

    Nora-Krūkle Zaiga

    2016-08-01

    Full Text Available Human bocavirus 1 (HBoV1 is a parvovirus recently found to be a possible aetiologic agent of acute respiratory disease in children. We conducted the first clinical and molecular study on this virus in Latvia (LV and Lithuania (LT. The aim of the study was to determine the occurrence of HBoV1 in respiratory tract samples taken from hospitalised children with acute respiratory tract infections in LV and LT. In total 186 children with age one to 50 months, and who fulfilled criteria of acute respiratory tract infection, including lower respiratory tract infections, with or without fever, were included in this study. A nasopharyngeal aspirate was obtained from each patient on admission. DNA was isolated and polimerase chain reaction (PCR performed targeting the HBoV1 NS1sequence. HBoV1 positive samples were sequenced and phylogenetic analysis was performed. HBoV1 sequence was detected in 42 (32% of 130 LV and in 8 (14% of 56 LT samples. In LV the majority of patients with HBoV1 infection were observed in February while in LT in October. The phylogenetic tree for HBoV1 indicated that isolates of HBoV1 cluster closely and include almost all of the isolates in this study. HBoV1 is common in Latvia and Lithuania and might be a significant pathogen that contributes to acute respiratory tract infections in children.

  5. Implications of the Secondary Eclipse of Exoplanet HAT-P-11b

    Science.gov (United States)

    Barry, Richard K.; Deming, L. D.; Bakos, G.; Harrington, J.; Madhusudhan, N.; Noyes, R.; Seager, S.

    2010-01-01

    We observed exoplanet HAT-P-11b and have successfully detected its secondary eclipse. We conducted observations using the Spitzer Space Telescope in the post-cryo mission at 3.6 microns for a period of 22 hours centered on the anticipated secondary eclipse time, to detect the eclipse and determine its phase. Having detected the secondary eclipse, we are at present making a more focused series of observations in both the 3.6 and 4.5 micron bands to fully characterize it. HAT-P-11b is one of only two known exo-Neptunes and has a period of 4.8878 days, radius of 0.422 RJ, mass of 0.081 MJ and semi-major axis 0.053 AU. Measurements of the secondary eclipse will serve to clarify two key issues; 1) the planetary brightness temperature and the nature of its atmosphere, and 2) the eccentricity of its orbit, with implications for its dynamical evolution. We discuss implications of these observations.

  6. Potential ground water resources of Hat Yai Basin in Peninsular Thailand by gravity study

    Directory of Open Access Journals (Sweden)

    Warawutti Lohawijarn

    2005-05-01

    Full Text Available Residual gravity anomaly with a minimum of about -140 mm s-2 with approximately NS trend and a limited axial length was observed over Hat Yai Basin in Peninsular Thailand. The modeled Hat Yai basin is about 1 km deep at its deepest, 60 km long and 20 km wide. The porosity of basin sediment and the amount of potential ground water reserves within the basin are estimated to be 39% and 121.7±0.8 km3 respectively, assuming full saturation. Within the topmost 80 m of ground where the present extraction is concentrated, the estimated ground water reserve is 12.5±0.5 km3.

  7. Choline acetyltransferase expression during periods of behavioral activity and across natural sleep-wake states in the basal forebrain.

    Science.gov (United States)

    Greco, M A; McCarley, R W; Shiromani, P J

    1999-01-01

    The present study examined whether the expression of the messenger RNA encoding the protein responsible for acetylcholine synthesis is associated with sleep-wakefulness. Choline acetyltransferase messenger RNA levels were analysed using a semi-quantitative assay in which reverse transcription was coupled to complementary DNA amplification using the polymerase chain reaction. To examine the relationship between steady-state messenger RNA and behavioral activity, rats were killed during the day (4.00 p.m.) or night (4.00 a.m.), and tissue from the vertical and horizontal limbs of the diagonal bands of Broca was analysed. Choline acetyltransferase messenger RNA levels were higher during the day than during the night. The second study examined more closely the association between choline acetyltransferase messenger RNA levels and individual bouts of wakefulness, slow-wave sleep or rapid eye movement sleep. Choline acetyltransferase messenger RNA levels were low during wakefulness, intermediate in slow-wave sleep and high during rapid eye movement sleep. In contrast, protein activity, measured at a projection site of cholinergic neurons of the basal forebrain, was higher during wakefulness than during sleep. These findings suggest that choline acetyltransferase protein and messenger RNA levels exhibit an inverse relationship during sleep and wakefulness. The increased messenger RNA expression during sleep is consistent with a restorative function of sleep.

  8. Species specific substrates and products choices of 4-O-acetyltransferase from Trichoderma brevicompactum.

    Science.gov (United States)

    Sharma, Shikha; Kumari, Indu; Hussain, Razak; Ahmed, Mushtaq; Akhter, Yusuf

    2017-09-01

    Antagonistic species of Trichoderma such as T. harzianum, T. viride, T. virens and T. koningii are well-known biocontrol agents that have been reported to suppress pathogenic soil microbes and enhance the growth of crop plants. Secondary metabolites (SMs) including trichothecenes are responsible for its biocontrol activities. The trichothecenes, trichodermin and harzianum A (HA) are produced in species dependent manner respectively, by Trichoderma brevicompactum (TB) and Trichoderma arundinaceum (TA). The last step in the pathway involves the conversion of trichodermol into trichodermin or HA alternatively, which is catalyzed by 4-O-acetyltransferase (encoded by tri3 gene). Comparative sequence analysis of acetyltransferase enzyme of TB with other chloramphenicol acetyltransferase (CAT) family proteins revealed the conserved motif involved in the catalysis. Multiple substrate binding studies were carried out to explore the mechanism behind the two different outcomes. His188 was found to have a role in initial substrate binding. In the case of trichodermin synthesis, represented by ternary complex 1, the trichodermol and acetic anhydride (AAn), the two substrates come very close to each other during molecular simulation analysis so that interactions become possible between them and acetyl group may get transferred from AAn to trichodermol, and Tyr476 residue mediates this phenomenon resulting in the formation of trichodermin. However, in case of the HA biosynthesis using the TB version of enzyme, represented by ternary complex 2, the two substrates, trichodermol and octa-2Z,4E,6E-trienedioic acid (OCTA) did not show any such interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Insight into cofactor recognition in arylamine N-acetyltransferase enzymes

    DEFF Research Database (Denmark)

    Xu, Ximing; Li de la Sierra-Gallay, Inés; Kubiak, Xavier Jean Philippe

    2015-01-01

    Arylamine N-acetyltransferases (NATs) are xenobiotic metabolizing enzymes that catalyze the acetyl-CoA-dependent acetylation of arylamines. To better understand the mode of binding of the cofactor by this family of enzymes, the structure of Mesorhizobium loti NAT1 [(RHILO)NAT1] was determined...... for Bacillus anthracis NAT1 and Homo sapiens NAT2. Therefore, in contrast to previous data, this study shows that different orthologous NATs can bind their cofactors in a similar way, suggesting that the mode of binding CoA in this family of enzymes is less diverse than previously thought. Moreover......, it supports the notion that the presence of the `mammalian/eukaryotic insertion loop' in certain NAT enzymes impacts the mode of binding CoA by imposing structural constraints....

  10. Effects of hyperbaric oxygen and normobaric carbogen on the radiation response of the rat rhabdomyosarcoma R1H

    International Nuclear Information System (INIS)

    Hartmann, K. Axel; Kleij, Ad J. van der; Carl, Ulrich M.; Hulshof, Maarten C.C.M.; Willers, Reinhart; Sminia, Peter

    2001-01-01

    Purpose: Hypoxic tumor cells are an important factor of radioresistance. Hyperbaric oxygen (HBO) and normobaric carbogen (95% oxygen, 5% carbon dioxide) increase the oxygen delivery to tumors. This study was performed to explore changes of tumor oxygenation during a course of fractionated irradiation and to determine the effectiveness of normobaric carbogen and HBO during the final phase of the radiation treatment. Methods and Materials: Experiments were performed on the rhabdomyosarcoma R1H growing on WAG/Rij rats. After 20 X-ray fractions of 2 Gy within 4 weeks, oxygen partial pressure (pO 2 ) was measured using the Eppendorf oxygen electrode under ambient conditions, with normobaric carbogen or HBO at a pressure of 240 kPa. Following the 4-week radiation course, a top-up dose of 10-50 Gy was applied in 2-10 fractions of 5 Gy with or without hyperoxygenation. Results: HBO but not carbogen significantly increased the median pO 2 in irradiated tumors. The radiation doses to control 50% of tumors were 38.0 Gy, 29.5 Gy, and 25.0 Gy for air, carbogen, and HBO, respectively. Both high oxygen content gas inspirations led to significantly improved tumor responses with oxygen enhancement ratios (OERs) of 1.3 for normobaric carbogen and 1.5 for HBO (air vs. carbogen: p=0.044; air vs. HBO: p=0.02; carbogen vs. HBO: p=0.048). Conclusion: Both normobaric carbogen and HBO significantly improved the radiation response of R1H tumors. HBO appeared to be more effective than normobaric carbogen, both with regard to tumor oxygenation and response to irradiation

  11. A Role for Histone Deacetylases in the Cellular and Behavioral Mechanisms Underlying Learning and Memory

    Science.gov (United States)

    Mahgoub, Melissa; Monteggia, Lisa M.

    2014-01-01

    Histone deacetylases (HDACs) are a family of chromatin remodeling enzymes that restrict access of transcription factors to the DNA, thereby repressing gene expression. In contrast, histone acetyltransferases (HATs) relax the chromatin structure allowing for an active chromatin state and promoting gene transcription. Accumulating data have…

  12. Clinical study on HAT and SEDAN score scales and related risk factors for predicting hemorrhagic transformation following thrombolysis in acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    Heng WEI

    2015-03-01

    Full Text Available Objective To investigate the value of HAT and SEDAN score scales in predicting hemorrhagic transformation (HT following the recombinant tissue-type plasminogen activator (rt-PA intravenous thrombolysis in acute ischemic stroke patients and risk factors affecting HT.  Methods A total of 143 patients with acute ischemic stroke underwent rt-PA intravenous thrombolysis within 4.50 h of onset and their clinical data were collected. According to head CT after thrombolysis, patients were divided into HT group (18 cases and non-HT group (125 cases. Single factor analysis was used to assess differences in HAT and SEDAN score scales and related risk factors of ischemic stroke in 2 groups, and further Logistic regression analysis was used to investigate independent predictors of HT. Receiver operating characteristic (ROC curve was used to evaluate the sensitivity and specificity of HAT and SEDAN score scales in predicting HT.  Results Univariate Logistic regression analysis showed that history of atrial fibrillation (AF, admission systolic blood pressure (SBP, admission blood glucose level, early low density of head CT, thrombolytic time window, National Institute of Health Stroke Scale (NIHSS, HAT and SEDAN scores were all risk factors for HT after thrombolysis (P < 0.05, for all. Multivariate Logistic regression analysis showed that history of AF (OR = 1.677, 95% CI: 1.332-2.111; P = 0.000, admission SBP (OR = 1.102, 95% CI: 1.009-1.204; P = 0.031, admission blood glucose level (OR = 1.870, 95% CI: 1.119-3.125; P = 0.017, thrombolysis time window (OR = 1.030, 95%CI: 1.009-1.052; P = 0.005, NIHSS score (OR = 1.574, 95%CI: 1.186-2.090; P = 0.002, HAT score (OR = 2.515, 95%CI: 1.273-4.970;P = 0.008 and SEDAN score (OR = 2.413, 95%CI: 1.123-5.185; P = 0.024 were risk factors for HT after thrombolysis. ROC curve analysis showed that HAT score could predict HT with 94.40% sensitivity and 41.60% specificity, and area under curve (AUC was 0.70. SEDAN

  13. Depletion of the human N-terminal acetyltransferase hNaa30 disrupts Golgi integrity and ARFRP1 localization.

    Science.gov (United States)

    Starheim, Kristian K; Kalvik, Thomas V; Bjørkøy, Geir; Arnesen, Thomas

    2017-04-30

    The organization of the Golgi apparatus (GA) is tightly regulated. Golgi stack scattering is observed in cellular processes such as apoptosis and mitosis, and has also been associated with disruption of cellular lipid metabolism and neurodegenerative diseases. Our studies show that depletion of the human N-α-acetyltransferase 30 (hNaa30) induces fragmentation of the Golgi stack in HeLa and CAL-62 cell lines. The GA associated GTPase ADP ribosylation factor related protein 1 (ARFRP1) was previously shown to require N-terminal acetylation for membrane association and based on its N-terminal sequence, it is likely to be a substrate of hNaa30. ARFRP1 is involved in endosome-to- trans -Golgi network (TGN) traffic. We observed that ARFRP1 shifted from a predominantly cis -Golgi and TGN localization to localizing both Golgi and non-Golgi vesicular structures in hNaa30-depleted cells. However, we did not observe loss of membrane association of ARFRP1. We conclude that hNaa30 depletion induces Golgi scattering and induces aberrant ARFRP1 Golgi localization. © 2017 The Author(s).

  14. Sequence analysis of the N-acetyltransferase 2 gene (NAT2) among ...

    African Journals Online (AJOL)

    Yazun Bashir Jarrar

    2017-11-26

    Nov 26, 2017 ... Sequence analysis of the N-acetyltransferase 2 gene (NAT2) among Jordanian volunteers, Libyan. Journal of Medicine .... For molecular modeling of NAT2 protein, visualized ..... cal clustering. .... cular dynamics simulation.

  15. Path representation of su-hat (2){sub k} states II: Operator construction of the fermionic character and spin-1/2 -RSOS factorization

    Energy Technology Data Exchange (ETDEWEB)

    Lamy-Poirier, Joel, E-mail: jlamypoirier@perimeterinstitute.c [Departement de Physique, de Genie Physique et d' Optique, Universite Laval, Quebec, Canada, G1V 0A6 (Canada); Mathieu, Pierre, E-mail: pmathieu@phy.ulaval.c [Departement de Physique, de Genie Physique et d' Optique, Universite Laval, Quebec, Canada, G1V 0A6 (Canada)

    2011-06-01

    This is the second of two articles (independent of each other) devoted to the analysis of the path description of the states in su-hat (2){sub k} WZW models. Here we present a constructive derivation of the fermionic character at level k based on these paths. The starting point is the expression of a path in terms of a sequence of nonlocal (formal) operators acting on the vacuum ground-state path. Within this framework, the key step is the construction of the level-k operator sequences out of those at level-1 by the action of a new type of operators. These actions of operators on operators turn out to have a path interpretation: these paths are precisely the finitized RSOS paths related to the unitary minimal models M(k+1,k+2). We thus unravel - at the level of the path representation of the states - a direct factorization into a k=1 spinon part times a RSOS factor. It is also pointed out that since there are two fermionic forms describing these finite RSOS paths, the resulting fermionic su-hat (2){sub k} characters arise in two versions. Finally, the relation between the present construction and the Nagoya spectral decomposition of the path space is sketched.

  16. N-acetyltransferase Mpr1 confers ethanol tolerance on Saccharomyces cerevisiae by reducing reactive oxygen species

    Energy Technology Data Exchange (ETDEWEB)

    Du, Xiaoyi [Fukui Prefectural Univ., Fukui (Japan). Dept. of Bioscience; Takagi, Hiroshi [Nara Inst. of Science and Technology, Ikoma, Nara (Japan). Graduate School of Biological Sciences

    2007-07-15

    N-Acetyltransferase Mpr1 of Saccharomyces cerevisiae can reduce intracellular oxidation levels and protect yeast cells under oxidative stress, including H{sub 2}O{sub 2}, heat-shock, or freeze-thaw treatment. Unlike many antioxidant enzyme genes induced in response to oxidative stress, the MPR1 gene seems to be constitutively expressed in yeast cells. Based on a recent report that ethanol toxicity is correlated with the production of reactive oxygen species (ROS), we examined here the role of Mpr1 under ethanol stress conditions. The null mutant of the MPR1 and MPR2 genes showed hypersensitivity to ethanol stress, and the expression of the MPR1 gene conferred stress tolerance. We also found that yeast cells exhibited increased ROS levels during exposure to ethanol stress, and that Mpr1 protects yeast cells from ethanol stress by reducing intracellular ROS levels. When the MPR1 gene was overexpressed in antioxidant enzyme-deficient mutants, increased resistance to H{sub 2}O{sub 2} or heat shock was observed in cells lacking the CTA1, CTT1, or GPX1 gene encoding catalase A, catalase T, or glutathione peroxidase, respectively. These results suggest that Mpr1 might compensate the function of enzymes that detoxify H{sub 2}O{sub 2}. Hence, Mpr1 has promising potential for the breeding of novel ethanol-tolerant yeast strains. (orig.)

  17. An Inactive Geminin Mutant That Binds Cdt1

    Directory of Open Access Journals (Sweden)

    Marissa Suchyta

    2015-05-01

    Full Text Available The initiation of DNA replication is tightly regulated in order to ensure that the genome duplicates only once per cell cycle. In vertebrate cells, the unstable regulatory protein Geminin prevents a second round of DNA replication by inhibiting the essential replication factor Cdt1. Cdt1 recruits mini-chromosome maintenance complex (MCM2-7, the replication helicase, into the pre-replication complex (pre-RC at origins of DNA replication. The mechanism by which Geminin inhibits MCM2-7 loading by Cdt1 is incompletely understood. The conventional model is that Geminin sterically hinders a direct physical interaction between Cdt1 and MCM2-7. Here, we describe an inactive missense mutant of Geminin, GemininAWA, which binds to Cdt1 with normal affinity yet is completely inactive as a replication inhibitor even when added in vast excess. In fact, GemininAWA can compete with GemininWT for binding to Cdt1 and prevent it from inhibiting DNA replication. GemininAWA does not inhibit the loading of MCM2-7 onto DNA in vivo, and in the presence of GemininAWA, nuclear DNA is massively over-replicated within a single S phase. We conclude that Geminin does not inhibit MCM loading by simple steric interference with a Cdt1-MCM2-7 interaction but instead works by a non-steric mechanism, possibly by inhibiting the histone acetyltransferase HBO1.

  18. Cinnamoyl compounds as simple molecules that inhibit p300 histone acetyltransferase.

    Science.gov (United States)

    Costi, Roberta; Di Santo, Roberto; Artico, Marino; Miele, Gaetano; Valentini, Paola; Novellino, Ettore; Cereseto, Anna

    2007-04-19

    Cinnamoly compounds 1a-c and 2a-d were designed, synthesized, and in vitro tested as p300 inhibitors. At different degrees, all tested compounds were proven to inactivate p300, particularly, derivative 2c was the most active inhibitor, also showing high specificity for p300 as compared to other histone acetyltransferases. Most notably, 2c showed anti-acetylase activity in mammalian cells. These compounds represent a new class of synthetic inhibitors of p300, characterized by simple chemical structures.

  19. Flexural fatigue life prediction of closed hat-section using materially nonlinear axial fatigue characteristics

    Science.gov (United States)

    Razzaq, Zia

    1989-01-01

    Straight or curved hat-section members are often used as structural stiffeners in aircraft. For instance, they are employed as stiffeners for the dorsal skin as well as in the aerial refueling adjacent area structure in F-106 aircraft. The flanges of the hat-section are connected to the aircraft skin. Thus, the portion of the skin closing the hat-section interacts with the section itself when resisting the stresses due to service loads. The flexural fatigue life of such a closed section is estimated using materially nonlinear axial fatigue characteristics. It should be recognized that when a structural shape is subjected to bending, the fatigue life at the neutral axis is infinity since the normal stresses are zero at that location. Conversely, the fatigue life at the extreme fibers where the normal bending stresses are maximum can be expected to be finite. Thus, different fatigue life estimates can be visualized at various distances from the neural axis. The problem becomes compounded further when significant portions away from the neutral axis are stressed into plastic range. A theoretical analysis of the closed hat-section subjected to flexural cyclic loading is first conducted. The axial fatigue characteristics together with the related axial fatigue life formula and its inverted form given by Manson and Muralidharan are adopted for an aluminum alloy used in aircraft construction. A closed-form expression for predicting the flexural fatigue life is then derived for the closed hat-section including materially nonlinear action. A computer program is written to conduct a study of the variables such as the thicknesses of the hat-section and the skin, and the type of alloy used. The study has provided a fundamental understanding of the flexural fatigue life characteristics of a practical structural component used in aircraft when materially nonlinear action is present.

  20. Planet-induced Stellar Pulsations in HAT-P-2's Eccentric System

    Energy Technology Data Exchange (ETDEWEB)

    Wit, Julien de [Department of Earth, Atmospheric and Planetary Sciences, MIT, 77 Massachusetts Avenue, Cambridge, MA 02139 (United States); Lewis, Nikole K. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Knutson, Heather A.; Batygin, Konstantin [Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125 (United States); Fuller, Jim [TAPIR, Walter Burke Institute for Theoretical Physics, Mailcode 350-17, California Institute of Technology, Pasadena, CA 91125 (United States); Antoci, Victoria [Stellar Astrophysics Centre, Department of Physics and Astronomy, Aarhus University, Ny Munkegade 120, DK-8000 Aarhus C (Denmark); Fulton, Benjamin J. [Institute for Astronomy, University of Hawaii, Honolulu, HI 96822 (United States); Laughlin, Gregory [Department of Astronomy, Yale University, New Haven, CT 06511 (United States); Deming, Drake [Department of Astronomy, University of Maryland at College Park, College Park, MD 20742 (United States); Shporer, Avi [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Pasadena, CA 91009 (United States); Cowan, Nicolas B. [Department of Physics, Department of Earth and Planetary Sciences, McGill University, 3550 rue University, Montreal, QC H3A 2A7 (Canada); Agol, Eric [Department of Astronomy, University of Washington, Seattle, WA 98195 (United States); Burrows, Adam S. [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Fortney, Jonathan J. [Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States); Langton, Jonathan [Department of Physics, Principia College, Elsah, IL 62028 (United States); Showman, Adam P. [Lunar and Planetary Laboratory, University of Arizona, Tucson, AZ 85721 (United States)

    2017-02-20

    Extrasolar planets on eccentric short-period orbits provide a laboratory in which to study radiative and tidal interactions between a planet and its host star under extreme forcing conditions. Studying such systems probes how the planet’s atmosphere redistributes the time-varying heat flux from its host and how the host star responds to transient tidal distortion. Here, we report the insights into the planet–star interactions in HAT-P-2's eccentric planetary system gained from the analysis of ∼350 hr of 4.5 μ m observations with the Spitzer Space Telescope . The observations show no sign of orbit-to-orbit variability nor of orbital evolution of the eccentric planetary companion, HAT-P-2 b. The extensive coverage allows us to better differentiate instrumental systematics from the transient heating of HAT-P-2 b’s 4.5 μ m photosphere and yields the detection of stellar pulsations with an amplitude of approximately 40 ppm. These pulsation modes correspond to exact harmonics of the planet’s orbital frequency, indicative of a tidal origin. Transient tidal effects can excite pulsation modes in the envelope of a star, but, to date, such pulsations had only been detected in highly eccentric stellar binaries. Current stellar models are unable to reproduce HAT-P-2's pulsations, suggesting that our understanding of the interactions at play in this system is incomplete.

  1. Mof-associated complexes have overlapping and unique roles in regulating pluripotency in embryonic stem cells and during differentiation

    Science.gov (United States)

    Ravens, Sarina; Fournier, Marjorie; Ye, Tao; Stierle, Matthieu; Dembele, Doulaye; Chavant, Virginie; Tora, Làszlò

    2014-01-01

    The histone acetyltransferase (HAT) Mof is essential for mouse embryonic stem cell (mESC) pluripotency and early development. Mof is the enzymatic subunit of two different HAT complexes, MSL and NSL. The individual contribution of MSL and NSL to transcription regulation in mESCs is not well understood. Our genome-wide analysis show that i) MSL and NSL bind to specific and common sets of expressed genes, ii) NSL binds exclusively at promoters, iii) while MSL binds in gene bodies. Nsl1 regulates proliferation and cellular homeostasis of mESCs. MSL is the main HAT acetylating H4K16 in mESCs, is enriched at many mESC-specific and bivalent genes. MSL is important to keep a subset of bivalent genes silent in mESCs, while developmental genes require MSL for expression during differentiation. Thus, NSL and MSL HAT complexes differentially regulate specific sets of expressed genes in mESCs and during differentiation. DOI: http://dx.doi.org/10.7554/eLife.02104.001 PMID:24898753

  2. HDAC Inhibition Modulates Hippocampus-Dependent Long-Term Memory for Object Location in a CBP-Dependent Manner

    Science.gov (United States)

    Haettig, Jakob; Stefanko, Daniel P.; Multani, Monica L.; Figueroa, Dario X.; McQuown, Susan C.; Wood, Marcelo A.

    2011-01-01

    Transcription of genes required for long-term memory not only involves transcription factors, but also enzymatic protein complexes that modify chromatin structure. Chromatin-modifying enzymes, such as the histone acetyltransferase (HAT) CREB (cyclic-AMP response element binding) binding protein (CBP), are pivotal for the transcriptional regulation…

  3. Histone acetyltransferase TGF-1 regulates Trichoderma atroviride secondary metabolism and mycoparasitism.

    Science.gov (United States)

    Gómez-Rodríguez, Elida Yazmín; Uresti-Rivera, Edith Elena; Patrón-Soberano, Olga Araceli; Islas-Osuna, María Auxiliadora; Flores-Martínez, Alberto; Riego-Ruiz, Lina; Rosales-Saavedra, María Teresa; Casas-Flores, Sergio

    2018-01-01

    Some filamentous fungi of the Trichoderma genus are used as biocontrol agents against airborne and soilborne phytopathogens. The proposed mechanism by which Trichoderma spp. antagonizes phytopathogens is through the release of lytic enzymes, antimicrobial compounds, mycoparasitism, and the induction of systemic disease-resistance in plants. Here we analyzed the role of TGF-1 (Trichoderma Gcn Five-1), a histone acetyltransferase of Trichoderma atroviride, in mycoparasitism and antibiosis against the phytopathogen Rhizoctonia solani. Trichostatin A (TSA), a histone deacetylase inhibitor that promotes histone acetylation, slightly affected T. atroviride and R. solani growth, but not the growth of the mycoparasite over R. solani. Application of TSA to the liquid medium induced synthesis of antimicrobial compounds. Expression analysis of the mycoparasitism-related genes ech-42 and prb-1, which encode an endochitinase and a proteinase, as well as the secondary metabolism-related genes pbs-1 and tps-1, which encode a peptaibol synthetase and a terpene synthase, respectively, showed that they were regulated by TSA. A T. atroviride strain harboring a deletion of tgf-1 gene showed slow growth, thinner and less branched hyphae than the wild-type strain, whereas its ability to coil around the R. solani hyphae was not affected. Δtgf-1 presented a diminished capacity to grow over R. solani, but the ability of its mycelium -free culture filtrates (MFCF) to inhibit the phytopathogen growth was enhanced. Intriguingly, addition of TSA to the culture medium reverted the enhanced inhibition growth of Δtgf-1 MFCF on R. solani at levels compared to the wild-type MFCF grown in medium amended with TSA. The presence of R. solani mycelium in the culture medium induced similar proteinase activity in a Δtgf-1 compared to the wild-type, whereas the chitinolytic activity was higher in a Δtgf-1 mutant in the absence of R. solani, compared to the parental strain. Expression of mycoparasitism

  4. Histone acetyltransferase TGF-1 regulates Trichoderma atroviride secondary metabolism and mycoparasitism.

    Directory of Open Access Journals (Sweden)

    Elida Yazmín Gómez-Rodríguez

    Full Text Available Some filamentous fungi of the Trichoderma genus are used as biocontrol agents against airborne and soilborne phytopathogens. The proposed mechanism by which Trichoderma spp. antagonizes phytopathogens is through the release of lytic enzymes, antimicrobial compounds, mycoparasitism, and the induction of systemic disease-resistance in plants. Here we analyzed the role of TGF-1 (Trichoderma Gcn Five-1, a histone acetyltransferase of Trichoderma atroviride, in mycoparasitism and antibiosis against the phytopathogen Rhizoctonia solani. Trichostatin A (TSA, a histone deacetylase inhibitor that promotes histone acetylation, slightly affected T. atroviride and R. solani growth, but not the growth of the mycoparasite over R. solani. Application of TSA to the liquid medium induced synthesis of antimicrobial compounds. Expression analysis of the mycoparasitism-related genes ech-42 and prb-1, which encode an endochitinase and a proteinase, as well as the secondary metabolism-related genes pbs-1 and tps-1, which encode a peptaibol synthetase and a terpene synthase, respectively, showed that they were regulated by TSA. A T. atroviride strain harboring a deletion of tgf-1 gene showed slow growth, thinner and less branched hyphae than the wild-type strain, whereas its ability to coil around the R. solani hyphae was not affected. Δtgf-1 presented a diminished capacity to grow over R. solani, but the ability of its mycelium -free culture filtrates (MFCF to inhibit the phytopathogen growth was enhanced. Intriguingly, addition of TSA to the culture medium reverted the enhanced inhibition growth of Δtgf-1 MFCF on R. solani at levels compared to the wild-type MFCF grown in medium amended with TSA. The presence of R. solani mycelium in the culture medium induced similar proteinase activity in a Δtgf-1 compared to the wild-type, whereas the chitinolytic activity was higher in a Δtgf-1 mutant in the absence of R. solani, compared to the parental strain. Expression

  5. HAT-P-16b: A Bayesian Atmospheric Retrieval

    Science.gov (United States)

    McIntyre, Kathleen; Harrington, Joseph; Blecic, Jasmina; Cubillos, Patricio; Challener, Ryan; Bakos, Gaspar

    2017-10-01

    HAT-P-16b is a hot (equilibrium temperature 1626 ± 40 K, assuming zero Bond albedo and efficient energy redistribution), 4.19 ± 0.09 Jupiter-mass exoplanet orbiting an F8 star every 2.775960 ± 0.000003 days (Buchhave et al 2010). We observed two secondary eclipses of HAT-P-16b using the 3.6 μm and 4.5 μm channels of the Spitzer Space Telescope's Infrared Array Camera (program ID 60003). We applied our Photometry for Orbits, Eclipses, and Transits (POET) code to produce normalized eclipse light curves, and our Bayesian Atmospheric Radiative Transfer (BART) code to constrain the temperature-pressure profiles and atmospheric molecular abundances of the planet. Spitzer is operated by the Jet Propulsion Laboratory, California Institute of Technology, under a contract with NASA. This work was supported by NASA Planetary Atmospheres grant NNX12AI69G and NASA Astrophysics Data Analysis Program grant NNX13AF38G.

  6. Saccharomyces cerevisiae Atf1p is an alcohol acetyltransferase and a thioesterase in vitro.

    Science.gov (United States)

    Nancolas, Bethany; Bull, Ian D; Stenner, Richard; Dufour, Virginie; Curnow, Paul

    2017-06-01

    The alcohol-O-acyltransferases are bisubstrate enzymes that catalyse the transfer of acyl chains from an acyl-coenzyme A (CoA) donor to an acceptor alcohol. In the industrial yeast Saccharomyces cerevisiae this reaction produces acyl esters that are an important influence on the flavour of fermented beverages and foods. There is also a growing interest in using acyltransferases to produce bulk quantities of acyl esters in engineered microbial cell factories. However, the structure and function of the alcohol-O-acyltransferases remain only partly understood. Here, we recombinantly express, purify and characterize Atf1p, the major alcohol acetyltransferase from S. cerevisiae. We find that Atf1p is promiscuous with regard to the alcohol cosubstrate but that the acyltransfer activity is specific for acetyl-CoA. Additionally, we find that Atf1p is an efficient thioesterase in vitro with specificity towards medium-chain-length acyl-CoAs. Unexpectedly, we also find that mutating the supposed catalytic histidine (H191) within the conserved HXXXDG active site motif only moderately reduces the thioesterase activity of Atf1p. Our results imply a role for Atf1p in CoA homeostasis and suggest that engineering Atf1p to reduce the thioesterase activity could improve product yields of acetate esters from cellular factories. © 2017 The Authors. Yeast published by John Wiley & Sons, Ltd. © 2017 The Authors. Yeast published by John Wiley & Sons, Ltd.

  7. The E1A proteins of all six human adenovirus subgroups target the p300/CBP acetyltransferases and the SAGA transcriptional regulatory complex

    International Nuclear Information System (INIS)

    Shuen, Michael; Avvakumov, Nikita; Torchia, Joe; Mymryk, Joe S.

    2003-01-01

    The N-terminal/conserved region 1 (CR1) portion of the human adenovirus (Ad) 5 E1A protein was previously shown to inhibit growth in the simple eukaryote Saccharomyces cerevisiae. We now demonstrate that the corresponding regions of the E1A proteins of Ad3,-4,-9,-12, and -40, which represent the remaining five Ad subgroups, also inhibit yeast growth. These results suggest that the E1A proteins of all six human Ad subgroups share a common cellular target(s) conserved in yeast. Growth inhibition induced by either full-length or the N-terminal/CR1 portion of Ad5 E1A was relieved by coexpression of the E1A binding portions of the mammalian p300, CBP, and pCAF acetyltransferases. Similarly, growth inhibition by the N-terminal/CR1 portions of the other Ad E1A proteins was suppressed by expression of the same regions of CBP or pCAF known to bind Ad5 E1A. The physical interaction of each of the different Ad E1A proteins with CBP, p300, and pCAF was confirmed in vitro. Furthermore, deletion of the gene encoding yGcn5, the yeast homolog of pCAF and a subunit of the SAGA transcriptional regulatory complex, restored growth in yeast expressing each of the different Ad E1A proteins. This indicates that the SAGA complex is a conserved target of all Ad E1A proteins. Our results demonstrate for the first time that the p300, CBP, and pCAF acetyltransferases are common targets for the E1A proteins of all six human Ad subgroups, highlighting the importance of these interactions for E1A function

  8. Highly acidic C-terminal domain of pp32 is required for the interaction with histone chaperone, TAF-Ibeta.

    Science.gov (United States)

    Lee, In-Seon; Oh, Sang-Min; Kim, Sung-Mi; Lee, Dong-Seok; Seo, Sang-Beom

    2006-12-01

    We have previously reported that INHAT (inhibitor of acetyltransferases) complex subunits, TAF (template activating factor)-Ialpha, TAF-Ibeta and pp32 can inhibit histone acetylation and HAT (histone acetyltransferase)-dependent transcription by binding to histones. Evidences are accumulating that INHAT complex subunits have important regulatory roles in various cellular activities such as replication, transcription, and apoptosis etc. However, how these subunits interact each other remains largely unknown. Using immunoprecipitation (IP) and protein-protein interaction assays with TAF-Ibeta and pp32 deletion mutant proteins, we identify INHAT complex subunits, TAF-Ibeta and pp32 interaction requires highly acidic C-terminal domain of pp32. We also show that the interaction between the INHAT complex subunits is stronger in the presence of histones. In this study, we report that the synergistic inhibition of HAT-mediated transcription by TAF-Ibeta and pp32 is dependent on the highly acidic C-terminal domain of pp32.

  9. Postsynaptic alpha-adrenergic receptors potentiate the beta-adrenergic stimulation of pineal serotonin N-acetyltransferase.

    OpenAIRE

    Klein, D C; Sugden, D; Weller, J L

    1983-01-01

    The role played by postsynaptic alpha-adrenergic receptors in the stimulation of pineal N-acetyltransferase (EC 2.3.1.5) and [3H]melatonin production was investigated in the rat. In vivo studies indicated that phenylephrine, an alpha-adrenergic agonist, potentiated and prolonged the effects of isoproterenol, a beta-adrenergic agonist. Similar observations were made in organ culture with glands devoid of functional nerve endings. In addition, a combination of 1 microM prazosin, an alpha 1-adre...

  10. Analysis of cis and trans Requirements for DNA Replication at the Right-End Hairpin of the Human Bocavirus 1 Genome.

    Science.gov (United States)

    Shen, Weiran; Deng, Xuefeng; Zou, Wei; Engelhardt, John F; Yan, Ziying; Qiu, Jianming

    2016-09-01

    Parvoviruses are single-stranded DNA viruses that use the palindromic structures at the ends of the viral genome for their replication. The mechanism of parvovirus replication has been studied mostly in the dependoparvovirus adeno-associated virus 2 (AAV2) and the protoparvovirus minute virus of mice (MVM). Here, we used human bocavirus 1 (HBoV1) to understand the replication mechanism of bocaparvovirus. HBoV1 is pathogenic to humans, causing acute respiratory tract infections, especially in young children under 2 years old. By using the duplex replicative form of the HBoV1 genome in human embryonic kidney 293 (HEK293) cells, we identified the HBoV1 minimal replication origin at the right-end hairpin (OriR). Mutagenesis analyses confirmed the putative NS1 binding and nicking sites within the OriR. Of note, unlike the large nonstructural protein (Rep78/68 or NS1) of other parvoviruses, HBoV1 NS1 did not specifically bind OriR in vitro, indicating that other viral and cellular components or the oligomerization of NS1 is required for NS1 binding to the OriR. In vivo studies demonstrated that residues responsible for NS1 binding and nicking are within the origin-binding domain. Further analysis identified that the small nonstructural protein NP1 is required for HBoV1 DNA replication at OriR. NP1 and other viral nonstructural proteins (NS1 to NS4) colocalized within the viral DNA replication centers in both OriR-transfected cells and virus-infected cells, highlighting a direct involvement of NP1 in viral DNA replication at OriR. Overall, our study revealed the characteristics of HBoV1 DNA replication at OriR, suggesting novel characteristics of autonomous parvovirus DNA replication. Human bocavirus 1 (HBoV1) causes acute respiratory tract infections in young children. The duplex HBoV1 genome replicates in HEK293 cells and produces progeny virions that are infectious in well-differentiated airway epithelial cells. A recombinant AAV2 vector pseudotyped with an HBoV1

  11. HATS-36b and 24 Other Transiting/Eclipsing Systems from the HATSouth-K2 Campaign 7 Program

    Science.gov (United States)

    Bayliss, D.; Hartman, J. D.; Zhou, G.; Bakos, G. Á.; Vanderburg, A.; Bento, J.; Mancini, L.; Ciceri, S.; Brahm, R.; Jordán, A.; Espinoza, N.; Rabus, M.; Tan, T. G.; Penev, K.; Bhatti, W.; de Val-Borro, M.; Suc, V.; Csubry, Z.; Henning, Th.; Sarkis, P.; Lázár, J.; Papp, I.; Sári, P.

    2018-03-01

    We report on the result of a campaign to monitor 25 HATSouth candidates using the Kepler space telescope during Campaign 7 of the K2 mission. We discover HATS-36b (EPIC 215969174b, K2-145b), an eccentric (e=0.105+/- 0.028) hot Jupiter with a mass of 3.216+/- 0.062 {M}{{J}} and a radius of 1.235+/- 0.043 {R}{{J}}, which transits a solar-type G0V star (V = 14.386) in a 4.1752-day period. We also refine the properties of three previously discovered HATSouth transiting planets (HATS-9b, HATS-11b, and HATS-12b) and search the K2 data for TTVs and additional transiting planets in these systems. In addition, we also report on a further three systems that remain as Jupiter-radius transiting exoplanet candidates. These candidates do not have determined masses, however pass all of our other vetting observations. Finally, we report on the 18 candidates that we are now able to classify as eclipsing binary or blended eclipsing binary systems based on a combination of the HATSouth data, the K2 data, and follow-up ground-based photometry and spectroscopy. These range in periods from 0.7 day to 16.7 days, and down to 1.5 mmag in eclipse depths. Our results show the power of combining ground-based imaging and spectroscopy with higher precision space-based photometry, and serve as an illustration as to what will be possible when combining ground-based observations with TESS data.

  12. Long-term surveillance plan for the Mexican Hat Disposal Site, Mexican Hat, Utah

    International Nuclear Information System (INIS)

    1996-02-01

    This plan describes the long-term surveillance activities for the Uranium Mill Tailings Remedial Action (UMTRA) Project disposal site at Mexican Hat, Utah. The U.S. Department of Energy (DOE) will carry out these activities to ensure that the disposal site continues to function as designed. This long-term surveillance plan (LTSP) was prepared as a requirement for acceptance under the U.S. Nuclear Regulatory Commission (NRC) general license for custody and long-term care of residual radioactive material (RRM). This LTSP (based on the DOE's Guidance for Implementing the UMTRA Project Long-term Surveillance Program), documents the land ownership interests and details how the long-term care of the disposal site will be accomplished

  13. ORBITAL PHASE VARIATIONS OF THE ECCENTRIC GIANT PLANET HAT-P-2b

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, Nikole K.; Showman, Adam P. [Department of Planetary Sciences and Lunar and Planetary Laboratory, The University of Arizona, Tucson, AZ 85721 (United States); Knutson, Heather A.; Desert, Jean-Michel; Kao, Melodie [Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125 (United States); Cowan, Nicolas B. [Center for Interdisciplinary Exploration and Research in Astrophysics and Department of Physics and Astronomy, Northwestern University, 2131 Tech Drive, Evanston, IL 60208 (United States); Laughlin, Gregory; Fortney, Jonathan J. [Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States); Burrows, Adam; Bakos, Gaspar A.; Hartman, Joel D. [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Deming, Drake [Department of Astronomy, University of Maryland, College Park, MD 20742 (United States); Crepp, Justin R. [Department of Physics, University of Notre Dame, Notre Dame, IN 46556 (United States); Mighell, Kenneth J. [National Optical Astronomy Observatories, Tucson, AZ 85726 (United States); Agol, Eric [Department of Astronomy, University of Washington, Seattle, WA 98195 (United States); Charbonneau, David [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Fischer, Debra A. [Department of Astronomy, Yale University, New Haven, CT 06511 (United States); Hinkley, Sasha; Johnson, John Asher [Department of Astrophysics, California Institute of Technology, MC 249-17, Pasadena, CA 91125 (United States); Howard, Andrew W., E-mail: nklewis@mit.edu [Institute for Astronomy, University of Hawaii, 2680 Woodlawn Drive, Honolulu, HI 96822 (United States); and others

    2013-04-01

    We present the first secondary eclipse and phase curve observations for the highly eccentric hot Jupiter HAT-P-2b in the 3.6, 4.5, 5.8, and 8.0 {mu}m bands of the Spitzer Space Telescope. The 3.6 and 4.5 {mu}m data sets span an entire orbital period of HAT-P-2b (P = 5.6334729 d), making them the longest continuous phase curve observations obtained to date and the first full-orbit observations of a planet with an eccentricity exceeding 0.2. We present an improved non-parametric method for removing the intrapixel sensitivity variations in Spitzer data at 3.6 and 4.5 {mu}m that robustly maps position-dependent flux variations. We find that the peak in planetary flux occurs at 4.39 {+-} 0.28, 5.84 {+-} 0.39, and 4.68 {+-} 0.37 hr after periapse passage with corresponding maxima in the planet/star flux ratio of 0.1138% {+-} 0.0089%, 0.1162% {+-} 0.0080%, and 0.1888% {+-} 0.0072% in the 3.6, 4.5, and 8.0 {mu}m bands, respectively. Our measured secondary eclipse depths of 0.0996% {+-} 0.0072%, 0.1031% {+-} 0.0061%, 0.071%{sub -0.013%}{sup +0.029,} and 0.1392% {+-} 0.0095% in the 3.6, 4.5, 5.8, and 8.0 {mu}m bands, respectively, indicate that the planet cools significantly from its peak temperature before we measure the dayside flux during secondary eclipse. We compare our measured secondary eclipse depths to the predictions from a one-dimensional radiative transfer model, which suggests the possible presence of a transient day side inversion in HAT-P-2b's atmosphere near periapse. We also derive improved estimates for the system parameters, including its mass, radius, and orbital ephemeris. Our simultaneous fit to the transit, secondary eclipse, and radial velocity data allows us to determine the eccentricity (e = 0.50910 {+-} 0.00048) and argument of periapse ({omega} = 188. Degree-Sign 09 {+-} 0. Degree-Sign 39) of HAT-P-2b's orbit with a greater precision than has been achieved for any other eccentric extrasolar planet. We also find evidence for a long

  14. Regioselective Acetylation of C21 Hydroxysteroids by the Bacterial Chloramphenicol Acetyltransferase I.

    Science.gov (United States)

    Mosa, Azzam; Hutter, Michael C; Zapp, Josef; Bernhardt, Rita; Hannemann, Frank

    2015-07-27

    Chloramphenicol acetyltransferase I (CATI) detoxifies the antibiotic chloramphenicol and confers a corresponding resistance to bacteria. In this study we identified this enzyme as a steroid acetyltransferase and designed a new and efficient Escherichia-coli-based biocatalyst for the regioselective acetylation of C21 hydroxy groups in steroids of pharmaceutical interest. The cells carried a recombinant catI gene controlled by a constitutive promoter. The capacity of the whole-cell system to modify different hydroxysteroids was investigated, and NMR spectroscopy revealed that all substrates were selectively transformed into the corresponding 21-acetoxy derivatives. The biotransformation was optimized, and the reaction mechanism is discussed on the basis of a computationally modeled substrate docking into the crystal structure of CATI. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Detection and monitoring of human bocavirus 1 infection by a new rapid antigen test

    Directory of Open Access Journals (Sweden)

    A.H.L. Bruning

    2016-05-01

    Full Text Available Clinically relevant diagnosis of human bocavirus 1 (HBoV1 is challenging, as the virus is frequently detected in asymptomatic patients, and cofindings with other respiratory viruses are common. The clinical value of current diagnostic methods, such as PCR, is therefore low, and alternative diagnostic strategies are needed. We describe for the first time the use of an antigen detection assay for the rapid identification of HBoV1 in a paediatric patient with respiratory tract infection symptoms. We estimate the duration of active HBoV1 infection to be 6 days.

  16. Thermodynamic studies of a HAT cycle and its components

    International Nuclear Information System (INIS)

    Nyberg, Bjoern; Thern, Marcus

    2012-01-01

    Highlights: → Performance maps for HAT cycles with different complexity are shown. → A suggestion, where to extract cooling air for the turbine is presented. → The influence of the makeup water on total efficiency is shown. → The optimal pressure level for intercooling is described. -- Abstract: The electric power grid contains more and more renewable power production such as wind and solar power. The use of renewable power sources increases the fluctuations in the power grid which increase the demand for highly efficient, fast-starting power-producing units that can cope with sudden production losses. One of the more innovative power plant cycles, that have the potential of competing with conventional combined power plants in efficiency but has a higher availability and faster start up time, is the Evaporative Gas Turbine (EvGT) or Humid Air Turbine (HAT). A thermodynamic evaluation of different HAT cycle layouts has been done in this paper. Each layout is evaluated separately which makes it possible to study different components individual contribution to the efficiency and specific power. The thermodynamic evaluation also shows that it is important to look at different cool-flow extracting positions. The effect of water temperature entering the cycle, called make-up water, and where it is introduced into the cycle has been evaluated. The make-up water temperature also affects the optimal pressure level for intercooling and it is shown that an optimal position can be decided considering design parameters of the compressor and the water circuit.

  17. Signatures of rocky planet engulfment in HAT-P-4. Implications for chemical tagging studies

    Science.gov (United States)

    Saffe, C.; Jofré, E.; Martioli, E.; Flores, M.; Petrucci, R.; Jaque Arancibia, M.

    2017-07-01

    Aims: We aim to explore the possible chemical signature of planet formation in the binary system HAT-P-4 by studying the trends of abundance vs. condensation temperature Tc. The star HAT-P-4 hosts a planet detected by transits, while its stellar companion does not have any detected planet. We also study the lithium content, which might shed light on the problem of Li depletion in exoplanet host stars. Methods: We derived for the first time both stellar parameters and high-precision chemical abundances by applying a line-by-line full differential approach. The stellar parameters were determined by imposing ionization and excitation equilibrium of Fe lines, with an updated version of the FUNDPAR program, together with ATLAS9 model atmospheres and the MOOG code. We derived detailed abundances of different species with equivalent widths and spectral synthesis with the MOOG program. Results: The exoplanet host star HAT-P-4 is found to be 0.1 dex more metal rich than its companion, which is one of the highest differences in metallicity observed in similar systems. This could have important implications for chemical tagging studies. We rule out a possible peculiar composition for each star, such as is the case for λ Boötis and δ Scuti, and neither is this binary a blue straggler. The star HAT-P-4 is enhanced in refractory elements relative to volatile when compared to its stellar companion. Notably, the Li abundance in HAT-P-4 is greater than that of its companion by 0.3 dex, which is contrary to the model that explains the Li depletion by the presence of planets. We propose a scenario where at the time of planet formation, the star HAT-P-4 locked the inner refractory material in planetesimals and rocky planets, and formed the outer gas giant planet at a greater distance. The refractories were then accreted onto the star, possibly as a result of the migration of the giant planet. This explains the higher metallicity, the higher Li content, and the negative Tc trend we

  18. ORBITAL PHASE VARIATIONS OF THE ECCENTRIC GIANT PLANET HAT-P-2b

    International Nuclear Information System (INIS)

    Lewis, Nikole K.; Showman, Adam P.; Knutson, Heather A.; Désert, Jean-Michel; Kao, Melodie; Cowan, Nicolas B.; Laughlin, Gregory; Fortney, Jonathan J.; Burrows, Adam; Bakos, Gáspár Á.; Hartman, Joel D.; Deming, Drake; Crepp, Justin R.; Mighell, Kenneth J.; Agol, Eric; Charbonneau, David; Fischer, Debra A.; Hinkley, Sasha; Johnson, John Asher; Howard, Andrew W.

    2013-01-01

    We present the first secondary eclipse and phase curve observations for the highly eccentric hot Jupiter HAT-P-2b in the 3.6, 4.5, 5.8, and 8.0 μm bands of the Spitzer Space Telescope. The 3.6 and 4.5 μm data sets span an entire orbital period of HAT-P-2b (P = 5.6334729 d), making them the longest continuous phase curve observations obtained to date and the first full-orbit observations of a planet with an eccentricity exceeding 0.2. We present an improved non-parametric method for removing the intrapixel sensitivity variations in Spitzer data at 3.6 and 4.5 μm that robustly maps position-dependent flux variations. We find that the peak in planetary flux occurs at 4.39 ± 0.28, 5.84 ± 0.39, and 4.68 ± 0.37 hr after periapse passage with corresponding maxima in the planet/star flux ratio of 0.1138% ± 0.0089%, 0.1162% ± 0.0080%, and 0.1888% ± 0.0072% in the 3.6, 4.5, and 8.0 μm bands, respectively. Our measured secondary eclipse depths of 0.0996% ± 0.0072%, 0.1031% ± 0.0061%, 0.071% -0.013% +0.029, and 0.1392% ± 0.0095% in the 3.6, 4.5, 5.8, and 8.0 μm bands, respectively, indicate that the planet cools significantly from its peak temperature before we measure the dayside flux during secondary eclipse. We compare our measured secondary eclipse depths to the predictions from a one-dimensional radiative transfer model, which suggests the possible presence of a transient day side inversion in HAT-P-2b's atmosphere near periapse. We also derive improved estimates for the system parameters, including its mass, radius, and orbital ephemeris. Our simultaneous fit to the transit, secondary eclipse, and radial velocity data allows us to determine the eccentricity (e = 0.50910 ± 0.00048) and argument of periapse (ω = 188.°09 ± 0.°39) of HAT-P-2b's orbit with a greater precision than has been achieved for any other eccentric extrasolar planet. We also find evidence for a long-term linear trend in the radial velocity data. This trend suggests the presence of

  19. Virtual Screening of Phytochemicals to Novel Target (HAT) Rtt109 in Pneumocystis Jirovecii using Bioinformatics Tools.

    Science.gov (United States)

    Sugumar, Ramya; Adithavarman, Abhinand Ponneri; Dakshinamoorthi, Anusha; David, Darling Chellathai; Ragunath, Padmavathi Kannan

    2016-03-01

    Pneumocystis jirovecii is a fungus that causes Pneumocystis pneumonia in HIV and other immunosuppressed patients. Treatment of Pneumocystis pneumonia with the currently available antifungals is challenging and associated with considerable adverse effects. There is a need to develop drugs against novel targets with minimal human toxicities. Histone Acetyl Transferase (HAT) Rtt109 is a potential therapeutic target in Pneumocystis jirovecii species. HAT is linked to transcription and is required to acetylate conserved lysine residues on histone proteins by transferring an acetyl group from acetyl CoA to form e-N-acetyl lysine. Therefore, inhibitors of HAT can be useful therapeutic options in Pneumocystis pneumonia. To screen phytochemicals against (HAT) Rtt109 using bioinformatics tool. The tertiary structure of Pneumocystis jirovecii (HAT) Rtt109 was modeled by Homology Modeling. The ideal template for modeling was obtained by performing Psi BLAST of the protein sequence. Rtt109-AcCoA/Vps75 protein from Saccharomyces cerevisiae (PDB structure 3Q35) was chosen as the template. The target protein was modeled using Swiss Modeler and validated using Ramachandran plot and Errat 2. Comprehensive text mining was performed to identify phytochemical compounds with antipneumonia and fungicidal properties and these compounds were filtered based on Lipinski's Rule of 5. The chosen compounds were subjected to virtual screening against the target protein (HAT) Rtt109 using Molegro Virtual Docker 4.5. Osiris Property Explorer and Open Tox Server were used to predict ADME-T properties of the chosen phytochemicals. Tertiary structure model of HAT Rtt 109 had a ProSA score of -6.57 and Errat 2 score of 87.34. Structure validation analysis by Ramachandran plot for the model revealed 97% of amino acids were in the favoured region. Of all the phytochemicals subjected to virtual screening against the target protein (HAT) Rtt109, baicalin exhibited highest binding affinity towards the

  20. Sequence analysis of the N-acetyltransferase 2 gene (NAT2) among ...

    African Journals Online (AJOL)

    Yazun Bashir Jarrar

    2017-11-26

    Nov 26, 2017 ... Sequence analysis of the N-acetyltransferase 2 gene (NAT2) among Jordanian volunteers. Yazun Bashir Jarrar, Ayat Ahmed Balasmeh and Wassan Jarrar. Department of Pharmacy, College of Pharmacy, AlZaytoonah University of Jordan, Amman, Jordan. ABSTRACT. The present study aimed to identify ...

  1. The Chromatin Regulator Brpf1 Regulates Embryo Development and Cell Proliferation*

    Science.gov (United States)

    You, Linya; Yan, Kezhi; Zou, Jinfeng; Zhao, Hong; Bertos, Nicholas R.; Park, Morag; Wang, Edwin; Yang, Xiang-Jiao

    2015-01-01

    With hundreds of chromatin regulators identified in mammals, an emerging issue is how they modulate biological and pathological processes. BRPF1 (bromodomain- and PHD finger-containing protein 1) is a unique chromatin regulator possessing two PHD fingers, one bromodomain and a PWWP domain for recognizing multiple histone modifications. In addition, it binds to the acetyltransferases MOZ, MORF, and HBO1 (also known as KAT6A, KAT6B, and KAT7, respectively) to promote complex formation, restrict substrate specificity, and enhance enzymatic activity. We have recently showed that ablation of the mouse Brpf1 gene causes embryonic lethality at E9.5. Here we present systematic analyses of the mutant animals and demonstrate that the ablation leads to vascular defects in the placenta, yolk sac, and embryo proper, as well as abnormal neural tube closure. At the cellular level, Brpf1 loss inhibits proliferation of embryonic fibroblasts and hematopoietic progenitors. Molecularly, the loss reduces transcription of a ribosomal protein L10 (Rpl10)-like gene and the cell cycle inhibitor p27, and increases expression of the cell-cycle inhibitor p16 and a novel protein homologous to Scp3, a synaptonemal complex protein critical for chromosome association and embryo survival. These results uncover a crucial role of Brpf1 in controlling mouse embryo development and regulating cellular and gene expression programs. PMID:25773539

  2. P300/CBP acts as a coactivator to cartilage homeoprotein-1 (Cart1), paired-like homeoprotein, through acetylation of the conserved lysine residue adjacent to the homeodomain.

    Science.gov (United States)

    Iioka, Takashi; Furukawa, Keizo; Yamaguchi, Akira; Shindo, Hiroyuki; Yamashita, Shunichi; Tsukazaki, Tomoo

    2003-08-01

    The paired-like homeoprotein, Cart1, is involved in skeletal development. We describe here that the general coactivator p300/CBP controls the transcription activity of Cart1 through acetylation of a lysine residue that is highly conserved in other homeoproteins. Acetylation of this residue increases the interaction between p300/CBP and Cart1 and enhances its transcriptional activation. Cart1 encodes a paired-like homeoprotein expressed selectively in chondrocyte lineage during embryonic development. Although its target gene remains unknown, gene disruption studies have revealed that Cart1 plays an important role for craniofacial bone formation as well as limb development by cooperating with another homeoprotein, Alx4. In this report, we study the functional involvement of p300/CBP, coactivators with intrinsic histone acetyltransferase (HAT) activity, in the transcriptional control of Cart1. To study the transcription activity of Cart1, a reporter construct containing a putative Cart1 binding site was transiently transfected with the expression vectors of each protein. The interaction between p300/CBP and Cart1 was investigated by glutathione S-transferase (GST) pull-down, yeast two-hybrid, and immunoprecipitation assays. In vitro acetylation assay was performed with the recombinant p300-HAT domain and Cart1 in the presence of acetyl-CoA. p300 and CBP stimulate Cart1-dependent transcription activity, and this transactivation is inhibited by E1A and Tax, oncoproteins that suppress the activity of p300/CBP. Cart1 binds to p300 in vivo and in vitro, and this requires the homeodomain of Cart 1 and N-terminal 139 amino acids of p300. Confocal microscopy analysis shows that Cart1 recruits overexpressed and endogenous p300 to a Cart1-specific subnuclear compartment. Cart1 is acetylated in vivo and sodium butyrate and trichostatin A, histone deacetylase inhibitors, markedly enhance the transcription activity of Cart1. Deletion and mutagenesis analysis identifies the 131st

  3. Hypoglycaemia in patients with type 1 and type 2 diabetes mellitus on insulin therapy. Results of the global HAT study in Argentina

    Directory of Open Access Journals (Sweden)

    José E. Costa Gil

    2017-12-01

    Full Text Available We describe the results of the HAT study in 433 Argentinean patients with type 1 diabetes (T1D and 823 with type 2 diabetes (T2D. HAT was an international non-interventional study assessing severe and non-severe hypoglycaemia in patients with T1D and T2D under insulin treatment through a two-part self-assessment questionnaire (retrospective and prospective. The annual incidence of at least one hypoglycaemic episode was 46 episode/patient/year in T1D and 14.2 in T2D (retrospective, 96.5 and 24.6 episode/patient/year in T1D and T2D, respectively (prospective. Hypoglycaemia affected quality of life (on a scale of 0-10 for fear of hypoglycaemia: 60% in T1D and 37.6% in T2D scored 5 to 10, daily life, occupational or academic performance (2.1% with T1D and 3.2% with T2D did not attend to their work after hypoglycaemia, and induced an increased use of health resources (T1D: 66.1% increased glucose monitoring, 60.5% food intake, 51% consultations, 3.5% hospital admissions; 60.5% reduced insulin and 20.9% exercises; T2D increased 46.2% glucose monitoring, 43.8% consultations, 38.6% food intake, 24.1% reduced and 13.9% skipped the insulin dose and 14.3% suspended exercises. Greater numbers of episodes were recorded in the prospective period. An instrument to assess hypoglycaemia in clinical practice and strategies to reduce their risk are required. It is also important to ask about the episodes and reinforce the education of patients and close relatives on hypoglycaemia prevention and treatment

  4. Monitoring of BTX by passive sampling in Hat Yai

    Directory of Open Access Journals (Sweden)

    Proespichaya Kanatharana

    2004-02-01

    Full Text Available Laboratory-built passive samplers were used for monitoring of trace benzene, toluene and xylene (BTX in Hat Yai from 28 July to 12 August, 2003. Sampler bottles contained activated Tenax TA 60/80 meshand a lab-built thermal well were developed and evaluated for the sampling and analysis of BTX. The sampling was carried out for two weeks before the passive samplers were thermally desorbed, trapped ina sampling loop by a laboratory built purge and trap system and analysed by gas chromatography (GC equipped with a flame ionization detector. After optimization and calibration, the developed method showed high selectivity, a good sensitivity with detection limits for BTX of 0.8, 1.1 and 13.0 µg/m3 respectively and an acceptable precision. Ambient BTX measurements were conducted at many monitoring site i.e. hot spots (high exposure, residential areas/work places (common exposure and park (low exposure. The concentration at hot spots range from 3.2 to 5.4 µg/m3 for benzene, 38.0 to 80.3 µg/m3 for toluene and 29.7 to 66.7 µg/m3 for xylene.The low BTX were found at the city periphery (Tesco-Lotus billboard sampling stations, roof level and in Hat Yai Municipal Park but no absolute background concentration could be defined. The monitoring results showed that at higher level from the street surface, the level of BTX tended to decrease and the BTX pollution built up along a street canyon (Sanehanuson Road according to the wind direction. The highest BTX were found at the underground parking, 23.5 725.1 and 267.9 µg/m3 respectively where both WHO guideline for Benzene (16.3 µg/m3 and Toluene (260 µg/m3 were exceeded.

  5. Crystal structure of homoserine O-acetyltransferase from Leptospira interrogans

    International Nuclear Information System (INIS)

    Wang Mingzhu; Liu Lin; Wang Yanli; Wei Zhiyi; Zhang Ping; Li Yikun; Jiang Xiaohua; Xu Hang; Gong Weimin

    2007-01-01

    Homoserine O-acetyltransferase (HTA, EC 2.3.1.31) initiates methionine biosynthesis pathway by catalyzing the transfer of acetyl group from acetyl-CoA to homoserine. This study reports the crystal structure of HTA from Leptospira interrogans determined at 2.2 A resolution using selenomethionyl single-wavelength anomalous diffraction method. HTA is modular and consists of two structurally distinct domains-a core α/β domain containing the catalytic site and a helical bundle called the lid domain. Overall, the structure fold belongs to α/β hydrolase superfamily with the characteristic 'catalytic triad' residues in the active site. Detailed structure analysis showed that the catalytic histidine and serine are both present in two conformations, which may be involved in the catalytic mechanism for acetyl transfer

  6. Mexican hat curve for hydrogen and antihydrogen-states in natural atom H

    CERN Document Server

    Van Hooydonk, G

    2004-01-01

    Molecular band spectra as well as atomic line spectra reveal a left-right symmetry for atoms (Van Hooydonk, Spectrochim. Acta A, 2000, 56, 2273 and CERN-Ext-2002-041). We now extract a Mexican hat shaped or double well curve from the line spectrum (Lyman ns1/2 singlets) of natural atom H. An H CSB theory and its oscillator contribution (1-0.5pi/n)esp2/nexp2 lead to unprecedented results for antihydrogen physics, ahead of the CERN AD-project on artificial antihydrogen.

  7. Influence of hyperbaric oxygen on biomechanics and structural bone matrix in type 1 diabetes mellitus rats.

    Directory of Open Access Journals (Sweden)

    Pedro Henrique Justino Oliveira Limirio

    Full Text Available The aim of this study was to evaluate the biomechanics and structural bone matrix in diabetic rats subjected to hyperbaric oxygen therapy (HBO.Twenty-four male rats were divided into the following groups: Control; Control + HBO; Diabetic, and Diabetic + HBO. Diabetes was induced with streptozotocin (STZ in the diabetic Groups. After 30 days, HBO was performed every 48h in HBO groups and all animals were euthanized 60 days after diabetic induction. The femur was submitted to a biomechanical (maximum strength, energy-to-failure and stiffness and Attenuated Total Reflectance Fourier transform infrared (ATR-FTIR analyses (crosslink ratio, crystallinity index, matrix-to-mineral ratio: Amide I + II/Hydroxyapatite (M:MI and Amide III + Collagen/HA (M:MIII.In biomechanical analysis, diabetic animals showed lower values of maximum strength, energy and stiffness than non-diabetic animals. However, structural strength and stiffness were increased in groups with HBO compared with non-HBO. ATR-FTIR analysis showed decreased collagen maturity in the ratio of crosslink peaks in diabetic compared with the other groups. The bone from the diabetic groups showed decreased crystallinity compared with non-diabetic groups. M:MI showed no statistical difference between groups. However, M:MIII showed an increased matrix mineral ratio in diabetic+HBO and control+HBO compared with control and diabetic groups. Correlations between mechanical and ATR-FTIR analyses showed significant positive correlation between collagen maturity and stiffness.Diabetes decreased collagen maturation and the mineral deposition process, thus reducing biomechanical properties. Moreover, the study showed that HBO improved crosslink maturation and increased maximum strength and stiffness in the femur of T1DM animals.

  8. Influence of hyperbaric oxygen on biomechanics and structural bone matrix in type 1 diabetes mellitus rats.

    Science.gov (United States)

    Limirio, Pedro Henrique Justino Oliveira; da Rocha Junior, Huberth Alexandre; Morais, Richarlisson Borges de; Hiraki, Karen Renata Nakamura; Balbi, Ana Paula Coelho; Soares, Priscilla Barbosa Ferreira; Dechichi, Paula

    2018-01-01

    The aim of this study was to evaluate the biomechanics and structural bone matrix in diabetic rats subjected to hyperbaric oxygen therapy (HBO). Twenty-four male rats were divided into the following groups: Control; Control + HBO; Diabetic, and Diabetic + HBO. Diabetes was induced with streptozotocin (STZ) in the diabetic Groups. After 30 days, HBO was performed every 48h in HBO groups and all animals were euthanized 60 days after diabetic induction. The femur was submitted to a biomechanical (maximum strength, energy-to-failure and stiffness) and Attenuated Total Reflectance Fourier transform infrared (ATR-FTIR) analyses (crosslink ratio, crystallinity index, matrix-to-mineral ratio: Amide I + II/Hydroxyapatite (M:MI) and Amide III + Collagen/HA (M:MIII)). In biomechanical analysis, diabetic animals showed lower values of maximum strength, energy and stiffness than non-diabetic animals. However, structural strength and stiffness were increased in groups with HBO compared with non-HBO. ATR-FTIR analysis showed decreased collagen maturity in the ratio of crosslink peaks in diabetic compared with the other groups. The bone from the diabetic groups showed decreased crystallinity compared with non-diabetic groups. M:MI showed no statistical difference between groups. However, M:MIII showed an increased matrix mineral ratio in diabetic+HBO and control+HBO compared with control and diabetic groups. Correlations between mechanical and ATR-FTIR analyses showed significant positive correlation between collagen maturity and stiffness. Diabetes decreased collagen maturation and the mineral deposition process, thus reducing biomechanical properties. Moreover, the study showed that HBO improved crosslink maturation and increased maximum strength and stiffness in the femur of T1DM animals.

  9. Effectiveness Of Six Thinking Hats Training In Improving The ...

    African Journals Online (AJOL)

    This study investigated the effectiveness of Six Thinking Hats Training in improving the psychological well- being of prisoners. The study consisted of 24 convicted prisoners whose ages ranged from 19-60 years with a mean of 22.50 years. A 2x2 experimental group design was adopted, and subjects were randomly ...

  10. BALTIMORE’S M.S. LEVY AND SONS: Straw Hat Makers to the World, 1870-1960

    Directory of Open Access Journals (Sweden)

    Jessica I. Elfenbein

    2008-01-01

    Full Text Available From 1860 to 1960, Baltimore was an important center of the men’s ready-to- wear clothing industries. German-speaking Jews created many businesses that manufactured and sold underwear, men’s suits, and specialty items like hats and umbrellas. The straw hat making firm started by M.S. Levy is an interesting example of a Baltimore-based, family-owned niche business that existedfor 90 years, through three generations ofa singlefamily. The M.S. Levy and Sons story has two main chapters. The first covers the period from its founding by Michael Simon Levy in the 1870s through his son Julius’ death in 1926. This is the story of ascension. A premonition about the coming popularity of straw hats, together with a small but important technological breakthrough, positioned a family and a small industry for significant expansion. The second period began in 1930 with the introduction of wool felt hats and the death of William, M.S. Levy’s oldest son, and includes the Great Depression, unionization, merger, third generation leadership, and finally, in 1959, the family’s withdrawal from the industry. This later period, as told by grandsons of the founder, is the story of struggle followed by decline.

  11. Dicty_cDB: Contig-U06794-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available opus laevis N-acetyltransferase... 179 7e-44 ( P41227 ) RecName: Full=N-terminal acetyltransferase compl...P2... 178 1e-43 (Q9QY36) RecName: Full=N-terminal acetyltransferase complex ARD1... 178 1e-43 AK009697_1( AK...3 (Q9UTI3) RecName: Full=N-terminal acetyltransferase A complex ca... 174 2e-42 D...( AL672002 |pid:none) Mouse DNA sequence from clone RP2... 152 6e-36 ( P07347 ) RecName: Full=N-terminal acetyltransferase A compl...867 |pid:none) Methanococcus maripaludis C6, c... 55 2e-06 ( Q03503 ) RecName: Full=N-terminal acetyltransferase C compl

  12. p300 Acetyltransferase Regulates Androgen Receptor Degradation and PTEN-Deficient Prostate Tumorigenesis

    NARCIS (Netherlands)

    Zhong, J.; Ding, L.; Bohrer, L.R.; Pan, Y.; Liu, P.; Zhang, J.; Sebo, T.J.; Karnes, R.J.; Tindall, D.J.; Deursen, J.M. van; Huang, H.

    2014-01-01

    Overexpression of the histone acetyltransferase p300 is implicated in the proliferation and progression of prostate cancer, but evidence of a causal role is lacking. In this study, we provide genetic evidence that this generic transcriptional coactivator functions as a positive modifier of prostate

  13. UMTRA project water sampling and analysis plan, Mexican Hat, Utah

    International Nuclear Information System (INIS)

    1994-04-01

    The Mexican Hat, Utah, Uranium Mill Tailings Remedial Action (UMTRA) Project site is a former uranium mill that is undergoing surface remediation in the form of on-site tailings stabilization. Contaminated surface materials from the Monument Valley, Arizona, UMTRA Project site have been transported to the Mexican Hat site and are being consolidated with the Mexican Hat tailings. The scheduled completion of the tailings disposal cell is August 1995. Water is found in two geologic units at the site: the Halgaito Shale Formation and the Honaker Trail Formation. The tailings rest on the Halgaito Shale, and water contained in that unit is a result of milling activities and, to a lesser extent, water released from the tailings from compaction during remedial action construction of the disposal cell. Water in the Halgaito Shale flows through fractures and discharges at seeps along nearby arroyos. Flow from the seeps will diminish as water drains from the unit. Ground water in the lower unit, the Honaker Trail Formation, is protected from contamination by an upward hydraulic gradient. There are no nearby water supply wells because of widespread poor background ground water quality and quantity, and the San Juan River shows no impacts from the site. This water sampling and analysis plan (WSAP) recommends sampling six seeps and one upgradient monitor well compared in the Honaker Trail Formation. Samples will be taken in April 1994 (representative of high group water levels) and September 1994 (representative of low ground water levels). Analyses will be performed on filtered samples for plume indicator parameters

  14. On variable geometric factor systems for top-hat electrostatic space plasma analyzers

    International Nuclear Information System (INIS)

    Collinson, Glyn A; Kataria, Dhiren O

    2010-01-01

    Even in the relatively small region of space that is the Earth's magnetosphere, ion and electron fluxes can vary by several orders of magnitude. Top-hat electrostatic analyzers currently do not possess the dynamic range required to sample plasma under all conditions. The purpose of this study was to compare, through computer simulation, three new electrostatic methods that would allow the sensitivity of a sensor to be varied through control of its geometric factor (GF) (much like an aperture on a camera). The methods studied were inner filter plates, split hemispherical analyzer (SHA) and top-cap electrode. This is the first discussion of the filter plate concept and also the first study where all three systems are studied within a common analyzer design, so that their relative merits could be fairly compared. Filter plates were found to have the important advantage that they facilitate the reduction in instrument sensitivity whilst keeping all other instrument parameters constant. However, it was discovered that filter plates have numerous disadvantages that make such a system impracticable for a top-hat electrostatic analyzer. It was found that both the top-cap electrode and SHA are promising variable geometric factor system (VGFS) concepts for implementation into a top-hat electrostatic analyzer, each with distinct advantages over the other

  15. Histone deacetylase inhibitors induced differentiation and accelerated mineralization of pulp-derived cells.

    LENUS (Irish Health Repository)

    Duncan, Henry F

    2012-03-01

    Histone deacetylase inhibitors (HDACis) alter the homeostatic balance between 2 groups of cellular enzymes, histone deacetylases (HDACs) and histone acetyltransferases (HATs), increasing transcription and influencing cell behavior. This study investigated the potential of 2 HDACis, valproic acid (VPA) and trichostatin A (TSA), to promote reparative processes in pulp cells as assayed by viability, cell cycle, and mineralization analyses.

  16. A research on the postural stability of a person wearing the lower limb exoskeletal robot by the HAT model.

    Science.gov (United States)

    Chang, Minsu; Kim, Yeongmin; Lee, Yoseph; Jeon, Doyoung

    2017-07-01

    This paper proposes a method of detecting the postural stability of a person wearing the lower limb exoskeletal robot with the HAT(Head-Arm-Trunk) model. Previous studies have shown that the human posture is stable when the CoM(Center of Mass) of the human body is placed on the BoS(Base of Support). In the case of the lower limb exoskeletal robot, the motion data, which are used for the CoM estimation, are acquired by sensors in the robot. The upper body, however, does not have sensors in each segment so that it may cause the error of the CoM estimation. In this paper, the HAT(Head-Arm-Trunk) model which combines head, arms, and torso into a single segment is considered because the motion of head and arms are unknown due to the lack of sensors. To verify the feasibility of HAT model, the reflecting markers are attached to each segment of the whole human body and the exact motion data are acquired by the VICON to compare the COM of the full body model and HAT model. The difference between the CoM with full body and that with HAT model is within 20mm for the various motions of head and arms. Based on the HAT model, the XCoM(Extrapolated Center of Mass) which includes the velocity of the CoM is used for prediction of the postural stability. The experiment of making unstable posture shows that the XCoM of the whole body based on the HAT model is feasible to detect the instance of postural instability earlier than the CoM by 20-250 msec. This result may be used for the lower limb exoskeletal robot to prepare for any action to prevent the falling down.

  17. Modulation of thyroid hormone receptor transactivation by the early region 1A (E1A-like inhibitor of differentiation 1 (EID1

    Directory of Open Access Journals (Sweden)

    Diana Vargas

    2008-01-01

    Full Text Available Transcriptional activation (TA mediated by the effect of thyroid hormones on target genes requires co-activator proteins such as the early region 1A (E1A associated 300 kDa binding protein (p300 and the cAMP response element binding protein (CREB binding protein (CBP, known as the p300/CBP complex, which acetylate histones 3 and 4 to allow transcriptional machinery access to the target gene promoter. Little is known on the role of p300 in thyroid hormone receptor (TR mediated TA but the E1A-like inhibitor of differentiation 1 (EID1, an inhibitor of p300 histone acetyltransferase (HAT, is a functional homolog of E1A and may inhibit myogenic differentiation factor D (MyoD transcriptional activity and reduces muscle cell differentiation. We evaluated the influence of EID1 on TR-mediated transcriptional activity using transfection and mammalian two-hybrid studies to show that EID1 may partially reduces TA activity of the TR receptor, probably due to p300 blockage since EID1 mutants cannot reduce TR-mediated TA. The EID1 does not affect the function of p160 co-activator proteins (160 kDa proteins of steroid receptor co-activators and is functionally independent of co-repressor proteins or TR binding. Summarizing, EID1 reduces TR-mediated transcriptional activity by blocking p300 and may play an important role in thyroid receptor activity in muscle and other tissues.

  18. Structure of the Hat Creek graben region: Implications for the structure of the Hat Creek graben and transfer of right-lateral shear from the Walker Lane north of Lassen Peak, northern California, from gravity and magnetic anomalies

    Science.gov (United States)

    Langenheim, Victoria; Jachens, Robert C.; Clynne, Michael A.; Muffler, L. J. Patrick

    2016-01-01

    Interpretation of magnetic and new gravity data provides constraints on the geometry of the Hat Creek Fault, the amount of right-lateral offset in the area between Mt. Shasta and Lassen Peak, and confirmation of the influence of pre-existing structure on Quaternary faulting. Neogene volcanic rocks coincide with short-wavelength magnetic anomalies of both normal and reversed polarity, whereas a markedly smoother magnetic field occurs over the Klamath Mountains and its Paleogene cover. Although the magnetic field over the Neogene volcanic rocks is complex, the Hat Creek Fault, which is one of the most prominent normal faults in the region and forms the eastern margin of the Hat Creek Valley, is marked by the eastern edge of a north-trending magnetic and gravity high 20-30 km long. Modeling of these anomalies indicates that the fault is a steeply dipping (~75-85°) structure. The spatial relationship of the fault as modeled by the potential-field data, the youngest strand of the fault, and relocated seismicity suggests that deformation continues to step westward across the valley, consistent with a component of right-lateral slip in an extensional environment. Filtered aeromagnetic data highlight a concealed magnetic body of Mesozoic or older age north of Hat Creek Valley. The body’s northwest margin strikes northeast and is linear over a distance of ~40 km. Within the resolution of the aeromagnetic data (1-2 km), we discern no right-lateral offset of this body. Furthermore, Quaternary faults change strike or appear to end, as if to avoid this concealed magnetic body and to pass along its southeast edge, suggesting that pre-existing crustal structure influenced younger faulting, as previously proposed based on gravity data.

  19. Modulation of Escherichia coli serine acetyltransferase catalytic activity in the cysteine synthase complex

    Czech Academy of Sciences Publication Activity Database

    Benoni, Roberto; De Bei, O.; Paredi, G.; Hayes, C. S.; Franko, N.; Mozzarelli, A.; Bettati, S.; Campanini, B.

    2017-01-01

    Roč. 591, č. 9 (2017), s. 1212-1224 ISSN 0014-5793 Institutional support: RVO:61388963 Keywords : cysteine synthase * protein - protein interaction * serine acetyltransferase Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 3.623, year: 2016

  20. Photoacoustically Measured Speeds of Sound of Liquid HBO2: On Unlocking the Fuel Potential of Boron

    Energy Technology Data Exchange (ETDEWEB)

    Bastea, S; Crowhurst, J; Armstrong, M; ., N T

    2010-03-24

    Elucidation of geodynamic, geochemical, and shock induced processes is often limited by challenges to accurately determine molecular fluid equations of state (EOS). High pressure liquid state reactions of carbon species underlie physiochemical mechanisms such as differentiation of planetary interiors, deep carbon sequestration, propellant deflagration, and shock chemistry. Here we introduce a versatile photoacoustic technique developed to measure accurate and precise speeds of sound (SoS) of high pressure molecular fluids and fluid mixtures. SoS of an intermediate boron oxide, HBO{sub 2} are measured up to 0.5 GPa along the 277 C isotherm. A polarized Exponential-6 interatomic potential form, parameterized using our SoS data, enables EOS determinations and corresponding semi-empirical evaluations of > 2000 C thermodynamic states including energy release from bororganic formulations. Our thermochemical model propitiously predicts boronated hydrocarbon shock Hugoniot results.

  1. Ideologiekritik des E-Learnings. Welchen Nutzen hat die Einführung von E-Learning?

    Directory of Open Access Journals (Sweden)

    Katharina Kaiser-Müller

    2015-03-01

    Full Text Available Vor etwa sieben Jahren hat das damalige Bundesministerium für Unterricht, Kunst und Kultur (bm:ukk, das seit 2014 Bundesministerium für Bildung und Frauen (BMBF genannt wird, verschiedene Maßnahmen im Blick auf neuen Medien – insbesondere im Blick auf das E-Learning – gesetzt, um einen Beitrag zur Vorbereitung der Lernenden auf eine Informations- und Wissensgesellschaft zu leisten. E-Learning wurde als Erfolgsfaktor für die Zukunft gesehen und mit der Begründung, es fördere das individuelle und selbst gesteuerte Lernen, gefördert. Die zentrale Frage ist dabei: Welchen Nutzen hat die Einführung von E-Learning? In diesem Artikel wird dahingehend aufgezeigt, dass E-Learning nicht wegen pädagogischem Bedarf, sondern durch ministeriell gesetzte Maßnahmen eingeführt wurde und dadurch – wenn auch nicht bewusst und schon gar nicht als solches kommuniziert – neoliberale Strukturen durchgesetzt wurden. Die Einführung von E-Learning hat somit für deren Akzeptanz gesorgt.

  2. Acetylation of Mammalian ADA3 Is Required for Its Functional Roles in Histone Acetylation and Cell Proliferation.

    Science.gov (United States)

    Mohibi, Shakur; Srivastava, Shashank; Bele, Aditya; Mirza, Sameer; Band, Hamid; Band, Vimla

    2016-10-01

    Alteration/deficiency in activation 3 (ADA3) is an essential component of specific histone acetyltransferase (HAT) complexes. We have previously shown that ADA3 is required for establishing global histone acetylation patterns and for normal cell cycle progression (S. Mohibi et al., J Biol Chem 287:29442-29456, 2012, http://dx.doi.org/10.1074/jbc.M112.378901). Here, we report that these functional roles of ADA3 require its acetylation. We show that ADA3 acetylation, which is dynamically regulated in a cell cycle-dependent manner, reflects a balance of coordinated actions of its associated HATs, GCN5, PCAF, and p300, and a new partner that we define, the deacetylase SIRT1. We use mass spectrometry and site-directed mutagenesis to identify major sites of ADA3 acetylated by GCN5 and p300. Acetylation-defective mutants are capable of interacting with HATs and other components of HAT complexes but are deficient in their ability to restore ADA3-dependent global or locus-specific histone acetylation marks and cell proliferation in Ada3-deleted murine embryonic fibroblasts (MEFs). Given the key importance of ADA3-containing HAT complexes in the regulation of various biological processes, including the cell cycle, our study presents a novel mechanism to regulate the function of these complexes through dynamic ADA3 acetylation. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  3. Possible detection of a bimodal cloud distribution in the atmosphere of HAT-P-32 A b from multiband photometry

    Science.gov (United States)

    Tregloan-Reed, J.; Southworth, J.; Mancini, L.; Mollière, P.; Ciceri, S.; Bruni, I.; Ricci, D.; Ayala-Loera, C.; Henning, T.

    2018-03-01

    We present high-precision photometry of eight separate transit events in the HAT-P-32 planetary system. One transit event was observed simultaneously by two telescopes of which one obtained a simultaneous multiband light curve in three optical bands, giving a total of 11 transit light curves. Due to the filter selection and in conjunction with using the defocused photometry technique, we were able to obtain an extremely high-precision, ground-based transit in the u band (350 nm), with an rms scatter of ≈1 mmag. All 11 transits were modelled using PRISM and GEMC, and the physical properties of the system calculated. We find the mass and radius of the host star to be 1.182 ± 0.041 M⊙ and 1.225 ± 0.015 R⊙, respectively. For the planet, we find a mass of 0.80 ± 0.14 MJup, a radius of 1.807 ± 0.022 RJup, and a density of 0.126 ± 0.023 ρJup. These values are consistent with those found in the literature. We also obtain a new orbital ephemeris for the system T0 = BJD/TDB 2 454 420.447187(96) + 2.15000800(10) × E. We measured the transmission spectrum of HAT-P-32 A b and compared it to theoretical transmission spectra. Our results indicate a bimodal cloud particle distribution consisting of Rayleigh-like haze and grey absorbing cloud particles within the atmosphere of HAT-P-32 A b.

  4. HAT-P-26b: A Neptune-mass exoplanet with a well-constrained heavy element abundance.

    Science.gov (United States)

    Wakeford, Hannah R; Sing, David K; Kataria, Tiffany; Deming, Drake; Nikolov, Nikolay; Lopez, Eric D; Tremblin, Pascal; Amundsen, David S; Lewis, Nikole K; Mandell, Avi M; Fortney, Jonathan J; Knutson, Heather; Benneke, Björn; Evans, Thomas M

    2017-05-12

    A correlation between giant-planet mass and atmospheric heavy elemental abundance was first noted in the past century from observations of planets in our own Solar System and has served as a cornerstone of planet-formation theory. Using data from the Hubble and Spitzer Space Telescopes from 0.5 to 5 micrometers, we conducted a detailed atmospheric study of the transiting Neptune-mass exoplanet HAT-P-26b. We detected prominent H 2 O absorption bands with a maximum base-to-peak amplitude of 525 parts per million in the transmission spectrum. Using the water abundance as a proxy for metallicity, we measured HAT-P-26b's atmospheric heavy element content ([Formula: see text] times solar). This likely indicates that HAT-P-26b's atmosphere is primordial and obtained its gaseous envelope late in its disk lifetime, with little contamination from metal-rich planetesimals. Copyright © 2017, American Association for the Advancement of Science.

  5. Histone acetyltransferase inhibitors antagonize AMP-activated protein kinase in postmortem glycolysis

    Directory of Open Access Journals (Sweden)

    Qiong Li

    2017-06-01

    Full Text Available Objective The purpose of this study was to investigate the influence of AMP-activated protein kinase (AMPK activation on protein acetylation and glycolysis in postmortem muscle to better understand the mechanism by which AMPK regulates postmortem glycolysis and meat quality. Methods A total of 32 mice were randomly assigned to four groups and intraperitoneally injected with 5-Aminoimidazole-4-carboxamide1-β-D-ribofuranoside (AICAR, a specific activator of AMPK, AICAR and histone acetyltransferase inhibitor II, or AICAR, Trichostatin A (TSA, an inhibitor of histone deacetylase I and II and Nicotinamide (NAM, an inhibitor of the Sirt family deacetylases. After mice were euthanized, the Longissimus dorsi muscle was collected at 0 h, 45 min, and 24 h postmortem. AMPK activity, protein acetylation and glycolysis in postmortem muscle were measured. Results Activation of AMPK by AICAR significantly increased glycolysis in postmortem muscle. At the same time, it increased the total acetylated proteins in muscle 45 min postmortem. Inhibition of protein acetylation by histone acetyltransferase inhibitors reduced AMPK activation induced increase in the total acetylated proteins and glycolytic rate in muscle early postmortem, while histone deacetylase inhibitors further promoted protein acetylation and glycolysis. Several bands of proteins were detected to be differentially acetylated in muscle with different glycolytic rates. Conclusion Protein acetylation plays an important regulatory role in postmortem glycolysis. As AMPK mediates the effects of pre-slaughter stress on postmortem glycolysis, protein acetylation is likely a mechanism by which antemortem stress influenced postmortem metabolism and meat quality though the exact mechanism is to be elucidated.

  6. HAT-P-68b: A Transiting Hot Jupiter Around a K5 Dwarf Star

    Science.gov (United States)

    Lindor, Bethlee; Hartman, Joel D.

    2018-01-01

    One of the main goals of the astrophysical society has been to detect sources of life outside of Earth. To aid this search, astronomers have spent the last 2 decades focused on the discovery and characterization of exoplanets. The most effective method for doing so has been transit photometry, wherein we measure the brightness of stars over periods of time. These measurements, or light curves, are later analyzed for dips in brightness caused by objects passing in front of the star. However, variations in these time series can also occur due to non-planetary systems and a meticulous process is needed to distinguish the planets from the various false positives that are detected. HATNet is one of many surveys involved in this endeavor, and in this work I analyze HAT-P-68. First, I model the system as a single star with a transiting planet and derive estimates of the stellar and planetary physical parameters. I also model HAT-P-68 as a number of a false positives such as a pair of stars in an eclipsing binary blended with a background star, and a planet-sized star orbiting a Sun-like star. In order to rule out the possibility that HAT-P-68 is a blend, I carried out a statistical blend analysis of the photometric data and find that all blend models tested can be ruled out. Thus, I conclude that HAT-P-68 is a system with a transiting hot jupiter and consider what future observations would be most promising to further characterize the system.

  7. Investigation of local heterogeneity of hbO2 and hb in working dog heart in situ under isovolemic hemodilution and critical coronary stenosis

    Science.gov (United States)

    Krug, Alfons; Kessler, Manfred D.; Khuri, Raja; Lust, Robert; Chitwood, Randolph

    1996-12-01

    A tissue spectrophotometer (EMPHO II) working with 70 micrometer micro lightguide sensors enables recording of spectra in the visible wavelength range (500 - 630 nm). During an initial period arterial hypoxia and hyperoxia were induced on working dog heart by mechanical ventilation with oxygen fractions (fiO2) of 0.1 and 0.5. Under these conditions the effects of low and high fiO2 on oxygenation distribution of intracapillary hemoglobin were investigated. In the second part of the experiment the relation between systemic hematocrit, local hemoglobin concentration, local hemoglobin oxygenation and the oxygen regulation mechanism were studied in detail. In the final part of the experiment the effect of critical coronary stenosis on hb and hbO2 was measured. Critical stenosis was achieved by partial clamping of the left anterior coronary artery (LAD).

  8. Needs and wishes of alumni and employers : Research into the requirements of the labour market for international competencies in the Bachelor programme HBO ICT of The Hague University of Applied Sciences

    NARCIS (Netherlands)

    Anneke Wieman

    2015-01-01

    The Hague University of Applied Sciences has high ambitions in the field of internationalisation. Two out of four priorities in the institutional policy touch this theme: global citizenship and internationalisation. In order to ensure that the curriculum of the new degree programme HBO ICT meets

  9. Crystallization of ornithine acetyltransferase from yeast by counter-diffusion and preliminary X-ray study

    Energy Technology Data Exchange (ETDEWEB)

    Maes, Dominique, E-mail: dominique.maes@vub.ac.be; Crabeel, Marjolaine [Laboratorium voor Ultrastructuur, Vrije Universiteit Brussel (VUB) and Vlaams Interuniversitair Instituut voor Biotechnologie (VIB), Pleinlaan 2, B-1050 Brussels (Belgium); Van de Weerdt, Cécile; Martial, Joseph [Laboratoire de Biologie Moléculaire et de Génie Génétique, Université de Liège, Allée de la Chimie 3, B-4000 Liège (Belgium); Peeters, Eveline; Charlier, Daniël [Erfelijkheidsleer en Microbiologie, Vrije Universiteit Brussel (VUB), Pleinlaan 2, B-1050 Brussels (Belgium); Decanniere, Klaas; Vanhee, Celine; Wyns, Lode; Zegers, Ingrid [Laboratorium voor Ultrastructuur, Vrije Universiteit Brussel (VUB) and Vlaams Interuniversitair Instituut voor Biotechnologie (VIB), Pleinlaan 2, B-1050 Brussels (Belgium)

    2006-12-01

    A study on the crystallization of ornithine acetyltransferase from yeast, catalysing the fifth step in microbial arginine synthesis, is presented. The use of the counter-diffusion technique removes the disorder present in one dimension in crystals grown by either batch or hanging-drop techniques. A study is presented on the crystallization of ornithine acetyltransferase from yeast, which catalyzes the fifth step in microbial arginine synthesis. The use of the counter-diffusion technique removes the disorder present in one dimension in crystals grown by either the batch or hanging-drop techniques. This makes the difference between useless crystals and crystals that allow successful determination of the structure of the protein. The crystals belong to space group P4, with unit-cell parameters a = b = 66.98, c = 427.09 Å, and a data set was collected to 2.76 Å.

  10. PP32 and SET/TAF-Iβ proteins regulate the acetylation of newly synthesized histone H4.

    Science.gov (United States)

    Saavedra, Francisco; Rivera, Carlos; Rivas, Elizabeth; Merino, Paola; Garrido, Daniel; Hernández, Sergio; Forné, Ignasi; Vassias, Isabelle; Gurard-Levin, Zachary A; Alfaro, Iván E; Imhof, Axel; Almouzni, Geneviève; Loyola, Alejandra

    2017-11-16

    Newly synthesized histones H3 and H4 undergo a cascade of maturation steps to achieve proper folding and to establish post-translational modifications prior to chromatin deposition. Acetylation of H4 on lysines 5 and 12 by the HAT1 acetyltransferase is observed late in the histone maturation cascade. A key question is to understand how to establish and regulate the distinct timing of sequential modifications and their biological significance. Here, we perform proteomic analysis of the newly synthesized histone H4 complex at the earliest time point in the cascade. In addition to known binding partners Hsp90 and Hsp70, we also identify for the first time two subunits of the histone acetyltransferase inhibitor complex (INHAT): PP32 and SET/TAF-Iβ. We show that both proteins function to prevent HAT1-mediated H4 acetylation in vitro. When PP32 and SET/TAF-Iβ protein levels are down-regulated in vivo, we detect hyperacetylation on lysines 5 and 12 and other H4 lysine residues. Notably, aberrantly acetylated H4 is less stable and this reduces the interaction with Hsp90. As a consequence, PP32 and SET/TAF-Iβ depleted cells show an S-phase arrest. Our data demonstrate a novel function of PP32 and SET/TAF-Iβ and provide new insight into the mechanisms regulating acetylation of newly synthesized histone H4. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. The MYST family histone acetyltransferase complex regulates stress resistance and longevity through transcriptional control of DAF-16/FOXO transcription factors.

    Science.gov (United States)

    Ikeda, Takako; Uno, Masaharu; Honjoh, Sakiko; Nishida, Eisuke

    2017-08-09

    The well-known link between longevity and the Sir2 histone deacetylase family suggests that histone deacetylation, a modification associated with repressed chromatin, is beneficial to longevity. However, the molecular links between histone acetylation and longevity remain unclear. Here, we report an unexpected finding that the MYST family histone acetyltransferase complex (MYS-1/TRR-1 complex) promotes rather than inhibits stress resistance and longevity in Caenorhabditis elegans Our results show that these beneficial effects are largely mediated through transcriptional up-regulation of the FOXO transcription factor DAF-16. MYS-1 and TRR-1 are recruited to the promoter regions of the daf-16 gene, where they play a role in histone acetylation, including H4K16 acetylation. Remarkably, we also find that the human MYST family Tip60/TRRAP complex promotes oxidative stress resistance by up-regulating the expression of FOXO transcription factors in human cells. Tip60 is recruited to the promoter regions of the foxo1 gene, where it increases H4K16 acetylation levels. Our results thus identify the evolutionarily conserved role of the MYST family acetyltransferase as a key epigenetic regulator of DAF-16/FOXO transcription factors. © 2017 The Authors.

  12. HAT-P-11b: A SUPER-NEPTUNE PLANET TRANSITING A BRIGHT K STAR IN THE KEPLER FIELD

    International Nuclear Information System (INIS)

    Bakos, G. A.; Torres, G.; Pal, A.; Hartman, J.; Noyes, R. W.; Latham, D. W.; Sasselov, D. D.; Sipocz, B.; Esquerdo, G. A.; Kovacs, Gabor; Fernandez, J.; Kovacs, Geza; Moor, A.; Fischer, D. A.; Isaacson, H.; Johnson, J. A.; Marcy, G. W.; Howard, A.; Butler, R. P.; Vogt, S.

    2010-01-01

    We report on the discovery of HAT-P-11b, the smallest radius transiting extrasolar planet (TEP) discovered from the ground, and the first hot Neptune discovered to date by transit searches. HAT-P-11b orbits the bright (V = 9.587) and metal rich ([Fe/H] = +0.31 ± 0.05) K4 dwarf star GSC 03561-02092 with P = 4.8878162 ± 0.0000071 days and produces a transit signal with depth of 4.2 mmag, the shallowest found by transit searches that is due to a confirmed planet. We present a global analysis of the available photometric and radial velocity (RV) data that result in stellar and planetary parameters, with simultaneous treatment of systematic variations. The planet, like its near-twin GJ 436b, is somewhat larger than Neptune (17 M + , 3.8 R + ) both in mass M p = 0.081 ± 0.009 M J (25.8 ± 2.9 M + ) and radius R p = 0.422 ± 0.014 R J (4.73 ± 0.16 R + ). HAT-P-11b orbits in an eccentric orbit with e = 0.198 ± 0.046 and ω = 355. 0 2 ± 17. 0 3, causing a reflex motion of its parent star with amplitude 11.6 ± 1.2 m s -1 , a challenging detection due to the high level of chromospheric activity of the parent star. Our ephemeris for the transit events is T c = 2454605.89132 ± 0.00032 (BJD), with duration 0.0957 ± 0.0012 days, and secondary eclipse epoch of 2454608.96 ± 0.15 days (BJD). The basic stellar parameters of the host star are M * = 0.809 +0.020 -0.027 M sun , R * = 0.752 ± 0.021 R sun , and T eff* = 4780 ± 50 K. Importantly, HAT-P-11 will lie on one of the detectors of the forthcoming Kepler mission; this should make possible fruitful investigations of the detailed physical characteristic of both the planet and its parent star at unprecedented precision. We discuss an interesting constraint on the eccentricity of the system by the transit light curve and stellar parameters. This will be particularly useful for eccentric TEPs with low-amplitude RV variations in Kepler's field. We also present a blend analysis, that for the first time treats the case of a

  13. Risks on N-acetyltransferase 2 and bladder cancer: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Zhu Z

    2015-12-01

    Full Text Available Zongheng Zhu,1 Jinshan Zhang,2 Wei Jiang,3 Xianjue Zhang,4 Youkong Li,4 Xiaoming Xu51Department of General Surgery, Huangshi Love & Health Hospital, Huangshi, 2Department of Tumor surgery, Huangshi Central Hospital, Huangshi, 3Department of Urinary Surgery, Huangshi No 5 Hospital, Huangshi, 4Department of Urinary Surgery Jingzhou Central Hospital, Jingzhou, 5Department of Bone Surgery, Jingzhou Central Hospital, Jingzhou, People’s Republic of ChinaBackground: It is known that bladder cancer disease is closely related to aromatic amine compounds, which could cause cancer by regulating of N-acetylation and N-acetyltransferase 1 and 2 (NAT1 and NAT2. The NAT2 slowed acetylation and would increase the risk of bladder cancer, with tobacco smoke being regarded as a risk factor for this increased risk. However, the relationship between NAT2 slow acetylation and bladder cancer is still debatable at present. This study aims to explore preliminarily correlation of NAT2 slow acetylation and the risk of bladder cancer.Methods: The articles were searched from PubMed, Cochran, McGrane English databases, CBM, CNKI, and other databases. The extraction of bladder cancer patients and a control group related with the NAT2 gene were detected by the state, and the referenced articles and publications were also used for data retrieval. Using a random effects model, the model assumes that the studies included in the analysis cases belong to the overall population in the study of random sampling, and considering the variables within and between studies. Data were analyzed using STATA Version 6.0 software, using the META module. According to the inclusion and exclusion criteria of the literature study, 20 independent studies are included in this meta-analysis.Results: The results showed that the individual differences of bladder cancer susceptibility might be part of the metabolism of carcinogens. Slow acetylation status of bladder cancer associated with the pooled

  14. Purification and characterization of an N alpha-acetyltransferase from Saccharomyces cerevisiae.

    Science.gov (United States)

    Lee, F J; Lin, L W; Smith, J A

    1988-10-15

    N alpha-Acetyltransferase, which catalyzes the transfer of an acetyl group from acetyl coenzyme A to the alpha-NH2 group of proteins and peptides, was isolated from Saccharomyces cerevisiae and demonstrated by protein sequence analysis to be NH2-terminally blocked. The enzyme was purified 4,600-fold to apparent homogeneity by successive purification steps using DEAE-Sepharose, hydroxylapatite, DE52 cellulose, and Affi-Gel blue. The Mr of the native enzyme was estimated to be 180,000 +/- 10,000 by gel filtration chromatography, and the Mr of each subunit was estimated to be 95,000 +/- 2,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme has a pH optimum near 9.0, and its pI is 4.3 as determined by chromatofocusing on Mono-P. The enzyme catalyzed the transfer of an acetyl group to various synthetic peptides, including human adrenocorticotropic hormone (ACTH) (1-24) and its [Phe2] analogue, yeast alcohol dehydrogenase I (1-24), yeast alcohol dehydrogenase II (1-24), and human superoxide dismutase (1-24). These peptides contain either Ser or Ala as NH2-terminal residues which together with Met are the most commonly acetylated NH2-terminal residues (Persson, B., Flinta, C., von Heijne, G., and Jornvall, H. (1985) Eur. J. Biochem. 152, 523-527). Yeast enolase, containing a free NH2-terminal Ala residue, is known not to be N alpha-acetylated in vivo (Chin, C. C. Q., Brewer, J. M., and Wold, F. (1981) J. Biol. Chem. 256, 1377-1384), and enolase (1-24), a synthetic peptide mimicking the protein's NH2 terminus, was not acetylated in vitro by yeast acetyltransferase. The enzyme did not catalyze the N alpha-acetylation of other synthetic peptides including ACTH(11-24), ACTH(7-38), ACTH(18-39), human beta-endorphin, yeast superoxide dismutase (1-24). Each of these peptides has an NH2-terminal residue which is rarely acetylated in proteins (Lys, Phe, Arg, Tyr, Val, respectively). Among a series of divalent cations, Cu2+ and Zn2+ were demonstrated to be

  15. DIY teleport hats - the consolation of technology

    DEFF Research Database (Denmark)

    Hansen, Lone Koefoed

    2009-01-01

    or biking there. This particular set is made in the free-form crochet style: there is no exact pattern to crochet from, instead you crochet in an iterative process alternating between crocheting and trying the hat on for size and pattern adaptations. Disclaimer: It is of course not a functioning device...... but it works well as a gift for someone you miss or someone who misses another person madly as it provides an opportunity to take some kind of action when ordinary options like driving, jetting or biking are not feasible even if the action is only symbolic....

  16. Six Thinking Hats and Social Workers' Innovative Competence: An Experimental Study

    Science.gov (United States)

    Azeez, Razaq Olugbenga

    2016-01-01

    Employees, no doubt, are the main force in organizations, and their innovative behaviours are vital for outcome efficacy. Innovative organisations, therefore, need creative employees who generate new ideas for product or process of innovation. This study investigated the effect of six thinking hats creativity technique on innovative competence of…

  17. Protein acetylation sites mediated by Schistosoma mansoni GCN5

    International Nuclear Information System (INIS)

    Moraes Maciel, Renata de; Furtado Madeiro da Costa, Rodrigo; Meirelles Bastosde Oliveira, Francisco; Rumjanek, Franklin David; Fantappie, Marcelo Rosado

    2008-01-01

    The transcriptional co-activator GCN5, a histone acetyltransferase (HAT), is part of large multimeric complexes that are required for chromatin remodeling and transcription activation. As in other eukaryotes, the DNA from the parasite Schistosome mansoni is organized into nucleosomes and the genome encodes components of chromatin-remodeling complexes. Using a series of synthetic peptides we determined that Lys-14 of histone H3 was acetylated by the recombinant SmGCN5-HAT domain. SmGCN5 was also able to acetylate schistosome non-histone proteins, such as the nuclear receptors SmRXR1 and SmNR1, and the co-activator SmNCoA-62. Electron microscopy revealed the presence of SmGCN5 protein in the nuclei of vitelline cells. Within the nucleus, SmGCN5 was found to be located in interchromatin granule clusters (IGCs), which are transcriptionally active structures. The data suggest that SmGCN5 is involved in transcription activation

  18. Hippocampal histone acetylation regulates object recognition and the estradiol-induced enhancement of object recognition.

    Science.gov (United States)

    Zhao, Zaorui; Fan, Lu; Fortress, Ashley M; Boulware, Marissa I; Frick, Karyn M

    2012-02-15

    Histone acetylation has recently been implicated in learning and memory processes, yet necessity of histone acetylation for such processes has not been demonstrated using pharmacological inhibitors of histone acetyltransferases (HATs). As such, the present study tested whether garcinol, a potent HAT inhibitor in vitro, could impair hippocampal memory consolidation and block the memory-enhancing effects of the modulatory hormone 17β-estradiol E2. We first showed that bilateral infusion of garcinol (0.1, 1, or 10 μg/side) into the dorsal hippocampus (DH) immediately after training impaired object recognition memory consolidation in ovariectomized female mice. A behaviorally effective dose of garcinol (10 μg/side) also significantly decreased DH HAT activity. We next examined whether DH infusion of a behaviorally subeffective dose of garcinol (1 ng/side) could block the effects of DH E2 infusion on object recognition and epigenetic processes. Immediately after training, ovariectomized female mice received bilateral DH infusions of vehicle, E2 (5 μg/side), garcinol (1 ng/side), or E2 plus garcinol. Forty-eight hours later, garcinol blocked the memory-enhancing effects of E2. Garcinol also reversed the E2-induced increase in DH histone H3 acetylation, HAT activity, and levels of the de novo methyltransferase DNMT3B, as well as the E2-induced decrease in levels of the memory repressor protein histone deacetylase 2. Collectively, these findings suggest that histone acetylation is critical for object recognition memory consolidation and the beneficial effects of E2 on object recognition. Importantly, this work demonstrates that the role of histone acetylation in memory processes can be studied using a HAT inhibitor.

  19. Effects of Human Parvovirus B19 and Bocavirus VP1 Unique Region on Tight Junction of Human Airway Epithelial A549 Cells

    Science.gov (United States)

    Chiu, Chun-Ching; Shi, Ya-Fang; Yang, Jiann-Jou; Hsiao, Yuan-Chao; Tzang, Bor-Show; Hsu, Tsai-Ching

    2014-01-01

    As is widely recognized, human parvovirus B19 (B19) and human bocavirus (HBoV) are important human pathogens. Obviously, both VP1 unique region (VP1u) of B19 and HBoV exhibit the secreted phospholipase A2 (sPLA2)-like enzymatic activity and are recognized to participate in the pathogenesis of lower respiratory tract illnesses. However, exactly how, both VP1u from B19 and HBoV affect tight junction has seldom been addressed. Therefore, this study investigates how B19-VP1u and HBoV-VP1u may affect the tight junction of the airway epithelial A549 cells by examining phospholipase A2 activity and transepithelial electrical resistance (TEER) as well as performing immunoblotting analyses. Experimental results indicate that TEER is more significantly decreased in A549 cells by treatment with TNF-α (10 ng), two dosages of B19-VP1u and BoV-VP1u (400 ng and 4000 ng) or bee venom PLA2 (10 ng) than that of the control. Accordingly, more significantly increased claudin-1 and decreased occludin are detected in A549 cells by treatment with TNF-α or both dosages of HBoV-VP1u than that of the control. Additionally, more significantly decreased Na+/K+ ATPase is observed in A549 cells by treatment with TNF-α, high dosage of B19-VP1u or both dosages of BoV-VP1u than that of the control. Above findings suggest that HBoV-VP1u rather than B19 VP1u likely plays more important roles in the disruption of tight junction in the airway tract. Meanwhile, this discrepancy appears not to be associated with the secreted phospholipase A2 (sPLA2)-like enzymatic activity. PMID:25268969

  20. Methamphetamine causes differential alterations in gene expression and patterns of histone acetylation/hypoacetylation in the rat nucleus accumbens.

    Directory of Open Access Journals (Sweden)

    Tracey A Martin

    Full Text Available Methamphetamine (METH addiction is associated with several neuropsychiatric symptoms. Little is known about the effects of METH on gene expression and epigenetic modifications in the rat nucleus accumbens (NAC. Our study investigated the effects of a non-toxic METH injection (20 mg/kg on gene expression, histone acetylation, and the expression of the histone acetyltransferase (HAT, ATF2, and of the histone deacetylases (HDACs, HDAC1 and HDAC2, in that structure. Microarray analyses done at 1, 8, 16 and 24 hrs after the METH injection identified METH-induced changes in the expression of genes previously implicated in the acute and longterm effects of psychostimulants, including immediate early genes and corticotropin-releasing factor (Crf. In contrast, the METH injection caused time-dependent decreases in the expression of other genes including Npas4 and cholecystokinin (Cck. Pathway analyses showed that genes with altered expression participated in behavioral performance, cell-to-cell signaling, and regulation of gene expression. PCR analyses confirmed the changes in the expression of c-fos, fosB, Crf, Cck, and Npas4 transcripts. To determine if the METH injection caused post-translational changes in histone markers, we used western blot analyses and identified METH-mediated decreases in histone H3 acetylated at lysine 9 (H3K9ac and lysine 18 (H3K18ac in nuclear sub-fractions. In contrast, the METH injection caused time-dependent increases in acetylated H4K5 and H4K8. The changes in histone acetylation were accompanied by decreased expression of HDAC1 but increased expression of HDAC2 protein levels. The histone acetyltransferase, ATF2, showed significant METH-induced increased in protein expression. These results suggest that METH-induced alterations in global gene expression seen in rat NAC might be related, in part, to METH-induced changes in histone acetylation secondary to changes in HAT and HDAC expression. The causal role that HATs and

  1. Environmental assessment of remedial action at the Mexican Hat uranium mill tailings site, Mexican Hat, Utah

    International Nuclear Information System (INIS)

    1987-10-01

    This document assesses the environmental impacts of the proposed remedial action at the Mexican Hat uranium mill tailings site located on the Navajo Reservation in southern Utah. The site covers 235 acres and contains 69 acres of tailings and several of the original mill structures. Remedial action must be performed in accordance with standards and with the concurrence of the US Nuclear Regulatory Commission and the Navajo Nation. The proposed action is to stabilize the tailings within the present tailings site by consolidating the tailings and associated contaminated soils into a recontoured pile. A radon barrier of compacted earth would be constructed over the pile, and various erosion control measures would be taken to assure the long-term stability of the pile. The no action alternative is also assessed in this document. 240 refs., 12 figs., 20 tabs

  2. Identification of a BET Family Bromodomain/Casein Kinase II/TAF-Containing Complex as a Regulator of Mitotic Condensin Function

    Directory of Open Access Journals (Sweden)

    Hyun-Soo Kim

    2014-03-01

    Full Text Available Condensin is a central regulator of mitotic genome structure with mutants showing poorly condensed chromosomes and profound segregation defects. Here, we identify NCT, a complex comprising the Nrc1 BET-family tandem bromodomain protein (SPAC631.02, casein kinase II (CKII, and several TAFs, as a regulator of condensin function. We show that NCT and condensin bind similar genomic regions but only briefly colocalize during the periods of chromosome condensation and decondensation. This pattern of NCT binding at the core centromere, the region of maximal condensin enrichment, tracks the abundance of acetylated histone H4, as regulated by the Hat1-Mis16 acetyltransferase complex and recognized by the first Nrc1 bromodomain. Strikingly, mutants in NCT or Hat1-Mis16 restore the formation of segregation-competent chromosomes in cells containing defective condensin. These results are consistent with a model where NCT targets CKII to chromatin in a cell-cycle-directed manner in order to modulate the activity of condensin during chromosome condensation and decondensation.

  3. Identification of a BET family bromodomain/casein kinase II/TAF-containing complex as a regulator of mitotic condensin function.

    Science.gov (United States)

    Kim, Hyun-Soo; Mukhopadhyay, Rituparna; Rothbart, Scott B; Silva, Andrea C; Vanoosthuyse, Vincent; Radovani, Ernest; Kislinger, Thomas; Roguev, Assen; Ryan, Colm J; Xu, Jiewei; Jahari, Harlizawati; Hardwick, Kevin G; Greenblatt, Jack F; Krogan, Nevan J; Fillingham, Jeffrey S; Strahl, Brian D; Bouhassira, Eric E; Edelmann, Winfried; Keogh, Michael-Christopher

    2014-03-13

    Condensin is a central regulator of mitotic genome structure with mutants showing poorly condensed chromosomes and profound segregation defects. Here, we identify NCT, a complex comprising the Nrc1 BET-family tandem bromodomain protein (SPAC631.02), casein kinase II (CKII), and several TAFs, as a regulator of condensin function. We show that NCT and condensin bind similar genomic regions but only briefly colocalize during the periods of chromosome condensation and decondensation. This pattern of NCT binding at the core centromere, the region of maximal condensin enrichment, tracks the abundance of acetylated histone H4, as regulated by the Hat1-Mis16 acetyltransferase complex and recognized by the first Nrc1 bromodomain. Strikingly, mutants in NCT or Hat1-Mis16 restore the formation of segregation-competent chromosomes in cells containing defective condensin. These results are consistent with a model where NCT targets CKII to chromatin in a cell-cycle-directed manner in order to modulate the activity of condensin during chromosome condensation and decondensation. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1

    Directory of Open Access Journals (Sweden)

    Zhao MZ

    2017-03-01

    Full Text Available Minzhi Zhao,* Haiyun Li,* Yan Ma, He Gong, Shu Yang, Qiaojun Fang, Zhiyuan Hu Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Abraxane (Abr, a US Food and Drug Administration-approved albumin-bound nanoparticle applied for the treatment of non-small-cell lung cancer, has been reported to be more effective than paclitaxel (PTX. To further understand the molecular mechanisms that produce this superior drug efficacy of Abr, a quantitative proteomic approach has been applied to investigate the global protein expression profiles of lung cancer cell A549 treated with Abr and PTX. Only one protein, namely, glucosamine 6-phosphate N-acetyltransferase 1 (GNA1, showed significant differential expression (P<0.05 in the cutoff of 2.0 fold, suggesting that Abr can be used safely as a substitute for PTX. GNA1 is a key enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine, which is an important donor substrate for N-linked glycosylation and has several important functions such as embryonic development and growth. Albumin plays a major role in the regulation of this protein. In summary, this study first shows that the superior drug effect of Abr is mainly due to the downregulation of GNA1, which causes proliferative delay and cell adhesion defect. It is also noteworthy that the deficiency of GNA1 might reduce insulin secretion which correlates with type 2 diabetes. Keywords: quantitative proteomics, nano-drug, drug efficacy, lung cancer, molecular mechanisms, abraxane

  5. Rapid quantitative assay for chloramphenicol acetyltransferase

    International Nuclear Information System (INIS)

    Neumann, J.R.; Morency, C.A.; Russian, K.O.

    1987-01-01

    Measuring the expression of exogenous genetic material in mammalian cells is commonly done by fusing the DNA of interest to a gene encoding an easily-detected enzyme. Chloramphenicol acetyltransferase(CAT) is a convenient marker because it is not normally found in eukaryotes. CAT activity has usually been detected using a thin-layer chromatographic separation followed by autoradiography. An organic solvent extraction-based method for CAT detection has also been described, as well as a procedure utilizing HPLC analysis. Building on the extraction technique, they developed a rapid sensitive kinetic method for measuring CAT activity in cell homogenates. The method exploits the differential organic solubility of the substrate ([ 3 H] or [ 14 C]acetyl CoA) and the product (labeled acetylchloramphenicol). The assay is a simple one-vial, two-phase procedure and requires no tedious manipulations after the initial setup. Briefly, a 0.25 ml reaction with 100mM Tris-HCL, 1mM chloramphenicol, 0.1mM [ 14 C]acetyl CoA and variable amounts of cell homogenate is pipetted into a miniscintillation vial, overlaid with 5 ml of a water-immiscible fluor, and incubated at 37 0 C. At suitable intervals the vial is counted and the CAT level is quantitatively determined as the rate of increase in counts/min of the labeled product as it diffuses into the fluor phase, compared to a standard curve. When used to measure CAT in transfected Balb 3T3 cells the method correlated well with the other techniques

  6. A Novel 6'-N-Aminoglycoside Acetyltransferase, AAC(6')-Ial, from a Clinical Isolate of Serratia marcescens.

    Science.gov (United States)

    Tada, Tatsuya; Miyoshi-Akiyama, Tohru; Shimada, Kayo; Dahal, Rajan K; Mishra, Shyam K; Ohara, Hiroshi; Kirikae, Teruo; Pokhrel, Bharat M

    2016-03-01

    Serratia marcescens IOMTU115 has a novel 6'-N-aminoglycoside acetyltransferase-encoding gene, aac(6')-Ial. The encoded protein AAC(6')-Ial has 146 amino acids, with 91.8% identity to the amino acid sequence of AAC(6')-Ic in S. marcescens SM16 and 97.3% identity to the amino acid sequence of AAC(6')-Iap in S. marcescens WW4. The minimum inhibitory concentrations of aminoglycosides for Escherichia coli expressing AAC(6')-Ial were similar to those for E. coli expressing AAC(6')-Ic or AAC(6')-Iap. Thin-layer chromatography showed that AAC(6')-Ial, AAC(6')-Ic, or AAC(6')-Iap acetylated all the aminoglycosides tested, except for apramycin, gentamicin, and lividomycin. Kinetics assays revealed that AAC(6')-Ial is a functional acetyltransferase against aminoglycosides. The aac(6')-Ial gene was located on chromosomal DNA.

  7. Spontaneous breaking of chiral symmetry, and eventually of parity, in a σ-model with two Mexican hats

    International Nuclear Information System (INIS)

    Giacosa, Francesco

    2010-01-01

    A σ-model with two linked Mexican hats is discussed. This scenario could be realized in low-energy QCD when the ground state and the first excited (pseudo)scalar mesons are included, and where not only in the subspace of the ground states, but also in that of the first excited states, a Mexican hat potential is present. This possibility can change some basic features of a low-energy hadronic theory of QCD. It is also shown that spontaneous breaking of parity can occur in the vacuum for some parameter choice of the model. (orig.)

  8. A distinct DGAT with sn-3 acetyltransferase activity that synthesizes unusual, reduced-viscosity oils in Euonymus and transgenic seeds.

    Science.gov (United States)

    Durrett, Timothy P; McClosky, Daniel D; Tumaney, Ajay W; Elzinga, Dezi A; Ohlrogge, John; Pollard, Mike

    2010-05-18

    Endosperm and embryo tissues from the seeds of Euonymus alatus (Burning Bush) accumulate high levels of 3-acetyl-1,2-diacyl-sn-glycerols (acTAGs) as their major storage lipids. In contrast, the aril tissue surrounding the seed produces long-chain triacylglycerols (lcTAGs) typical of most other organisms. The presence of the sn-3 acetyl group imparts acTAGs with different physical and chemical properties, such as a 30% reduction in viscosity, compared to lcTAGs. Comparative transcriptome analysis of developing endosperm and aril tissues using pyrosequencing technology was performed to isolate the enzyme necessary for the synthesis of acTAGs. An uncharacterized membrane-bound O-acyltransferase (MBOAT) family member was the most abundant acyltransferase in the endosperm but was absent from the aril. Expression of this MBOAT in yeast resulted in the accumulation of acTAGs but not lcTAG; hence, the enzyme was named EaDAcT (Euonymus alatus diacylglycerol acetyltransferase). Yeast microsomes expressing EaDAcT possessed acetyl-CoA diacylglycerol acetyltransferase activity but lacked long-chain acyl-CoA diacylglycerol acyltransferase activity. Expression of EaDAcT under the control of a strong, seed-specific promoter in Arabidopsis resulted in the accumulation of acTAGs, up to 40 mol % of total TAG in the seed oil. These results demonstrate the utility of deep transcriptional profiling with multiple tissues as a gene discovery strategy for low-abundance proteins. They also show that EaDAcT is the acetyltransferase necessary and sufficient for the production of acTAGs in Euonymus seeds, and that this activity can be introduced into the seeds of other plants, allowing the evaluation of these unusual TAGs for biofuel and other applications.

  9. Wie viel Kapazität hat ein Mobilfunknetz?

    Science.gov (United States)

    Eisenblätter, Andreas; Geerdes, Hans-Florian

    Wer hat das noch nicht erlebt? Der Akku ist aufgeladen und reichlich Guthaben vorhanden, doch das Telefonieren mit dem Handy klappt trotzdem nicht. Meist liegt das daran, dass man sich in einem Funkloch befindet. Aber manchmal ist auch das Netz überlastet. Anders gesagt: das Funknetz des Mobilfunkanbieters, das viele Antennen auf Hausdächern oder Masten umfasst, bietet entweder nicht genügend Abdeckung oder nicht genügend Kapazität. Genau das will der Anbieter natürlich vermeiden. Mathematik hilft, diese Herausforderungen mit einer guten Planung des Mobilfunknetzes zu bewältigen.

  10. Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours

    Energy Technology Data Exchange (ETDEWEB)

    Lasko, Loren M.; Jakob, Clarissa G.; Edalji, Rohinton P.; Qiu, Wei; Montgomery, Debra; Digiammarino, Enrico L.; Hansen, T. Matt; Risi, Roberto M.; Frey, Robin; Manaves, Vlasios; Shaw, Bailin; Algire, Mikkel; Hessler, Paul; Lam, Lloyd T.; Uziel, Tamar; Faivre, Emily; Ferguson, Debra; Buchanan, Fritz G.; Martin, Ruth L.; Torrent, Maricel; Chiang, Gary G.; Karukurichi, Kannan; Langston, J. William; Weinert, Brian T.; Choudhary, Chunaram; de Vries, Peter; Van Drie, John H.; McElligott, David; Kesicki, Ed; Marmorstein, Ronen; Sun, Chaohong; Cole, Philip A.; Rosenberg, Saul H.; Michaelides, Michael R.; Lai, Albert; Bromberg, Kenneth D. (AbbVie); (UCopenhagen); (Petra Pharma); (UPENN); (JHU); (Van Drie); (Faraday)

    2017-09-27

    The dynamic and reversible acetylation of proteins, catalysed by histone acetyltransferases (HATs) and histone deacetylases (HDACs), is a major epigenetic regulatory mechanism of gene transcription1 and is associated with multiple diseases. Histone deacetylase inhibitors are currently approved to treat certain cancers, but progress on the development of drug-like histone actyltransferase inhibitors has lagged behind2. The histone acetyltransferase paralogues p300 and CREB-binding protein (CBP) are key transcriptional co-activators that are essential for a multitude of cellular processes, and have also been implicated in human pathological conditions (including cancer3). Current inhibitors of the p300 and CBP histone acetyltransferase domains, including natural products4, bi-substrate analogues5 and the widely used small molecule C6466,7, lack potency or selectivity. Here, we describe A-485, a potent, selective and drug-like catalytic inhibitor of p300 and CBP. We present a high resolution (1.95 Å) co-crystal structure of a small molecule bound to the catalytic active site of p300 and demonstrate that A-485 competes with acetyl coenzyme A (acetyl-CoA). A-485 selectively inhibited proliferation in lineage-specific tumour types, including several haematological malignancies and androgen receptor-positive prostate cancer. A-485 inhibited the androgen receptor transcriptional program in both androgen-sensitive and castration-resistant prostate cancer and inhibited tumour growth in a castration-resistant xenograft model. These results demonstrate the feasibility of using small molecule inhibitors to selectively target the catalytic activity of histone acetyltransferases, which may provide effective treatments for transcriptional activator-driven malignancies and diseases.

  11. Remedial Action Plan for the codisposal and stabilization of the Monument Valley and Mexican Hat uranium mill tailings at Mexican Hat, Utah: Appendices C--E. Final report

    International Nuclear Information System (INIS)

    1993-02-01

    This document provides appendices C, D, and E this Remedial Action Plan (RAP) which is a revision of the original Mexican Hat Remedial Action Plan and RAP Modification submitted in July 1988 and January 1989, respectively, along with updated design documents. Appendix C provide the Radiological Support Plan, Appendix D provides the Site Characterization, and Appendix E provides the Water Resources Protection Strategy

  12. Remedial Action Plan for the codisposal and stabilization of the Monument Valley and Mexican Hat uranium mill tailings at Mexican Hat, Utah: Appendices C--E. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-02-01

    This document provides appendices C, D, and E this Remedial Action Plan (RAP) which is a revision of the original Mexican Hat Remedial Action Plan and RAP Modification submitted in July 1988 and January 1989, respectively, along with updated design documents. Appendix C provide the Radiological Support Plan, Appendix D provides the Site Characterization, and Appendix E provides the Water Resources Protection Strategy.

  13. REFINED SYSTEM PARAMETERS AND TTV STUDY OF TRANSITING EXOPLANETARY SYSTEM HAT-P-20

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Leilei; Gu, Shenghong; Wang, Xiaobin; Cao, Dongtao; Wang, Yibo; Xiang, Yue [Yunnan Observatories, Chinese Academy of Sciences, Kunming 650011 (China); Cameron, Andrew Collier [School of Physics and Astronomy, University of St Andrews, North Haugh, St Andrews, Fife KY16 9SS (United Kingdom); Hui, Ho-Keung; Kwok, Chi-Tai [Ho Koon Nature Education cum Astronomical Centre, Sik Sik Yuen, Hong Kong (China); Yeung, Bill; Ng, Eric [Hong Kong Astronomical Society, Hong Kong (China); Horta, Ferran Grau, E-mail: wangxb@ynao.ac.cn [Observatori Ca l’Ou, C/de Dalt 18, Sant Martí Sesgueioles (Spain)

    2017-01-01

    We report new photometric observations of the transiting exoplanetary system HAT-P-20, obtained using CCD cameras at Yunnan Observatories and Ho Koon Nature Education cum Astronomical Centre, China, from 2010 to 2013, and Observatori Ca l’Ou, Sant Marti Sesgueioles, Spain, from 2013 to 2015. The observed data are corrected for systematic errors according to the coarse de-correlation and SYSREM algorithms, so as to enhance the signal of the transit events. In order to consistently model the star spots and transits of this exoplanetary system, we develop a highly efficient tool STMT based on the analytic models of Mandel and Agol and Montalto et al. The physical parameters of HAT-P-20 are refined by homogeneously analyzing our new data, the radial velocity data, and the earlier photometric data in the literature with the Markov chain Monte Carlo technique. New radii and masses of both host star and planet are larger than those in the discovery paper due to the discrepancy of the radius among K-dwarfs between predicted values by standard stellar models and empirical calibration from observations. Through the analysis of all available mid-transit times calculated with the normal model and spotted model, we conclude that the periodic transit timing variations in these transit events revealed by employing the normal model are probably induced by spot crossing events. From the analysis of the distribution of occulted spots by HAT-P-20b, we constrain the misaligned architecture between the planetary orbit and the spin of the host star.

  14. Photoacoustically Measured Speeds of Sound and the Equation of State of HBO2: On Understanding Detonation with Boron Fuel

    Energy Technology Data Exchange (ETDEWEB)

    Zaug, J M; Bastea, S; Crowhurst, J; Armstrong, M; Fried, L; Teslich, N

    2010-03-09

    Elucidation of geodynamic, geochemical, and shock induced processes is limited by challenges to accurately determine molecular fluid equations of state (EOS). High pressure liquid state reactions of carbon species underlie physiochemical mechanisms such as differentiation of planetary interiors, deep carbon sequestration, propellant deflagration, and shock chemistry. In this proceedings paper we introduce a versatile photoacoustic technique developed to measure accurate and precise speeds of sound (SoS) of high pressure molecular fluids and fluid mixtures. SoS of an intermediate boron oxide, HBO{sub 2} are measured up to 0.5 GPa along the 277 C isotherm. A polarized exponential-6 interatomic potential form, parameterized using our SoS data, enables EOS determinations and corresponding semi-empirical evaluations of >2000 C thermodynamic states including energy release from bororganic formulations. Our thermochemical model propitiously predicts boronated hydrocarbon shock Hugoniot results.

  15. Exercise enhances cognitive function and neurotrophin expression in the hippocampus accompanied by changes in epigenetic programming in senescence-accelerated mice.

    Science.gov (United States)

    Maejima, Hiroshi; Kanemura, Naohiko; Kokubun, Takanori; Murata, Kenji; Takayanagi, Kiyomi

    2018-02-05

    Aerobic exercise is known to increase expression of neurotrophins, particularly brain-derived neurotrophic factor (BDNF), in the hippocampus and to improve cognitive function. Exercise exerts neuroprotective effects in the hippocampus by inducing epigenetic changes, which play crucial roles in aging and neurodegenerative diseases. Specifically, the activity levels of histone acetyltransferases (HATs) and histone deacetylases (HDACs) regulate histone acetylation and modulate gene transcription. The objective of the present study was to assess the interactive effects of exercise and aging on cognitive function, expression of neurotrophins (BDNF and neurotrophin-4) and their receptors (tyrosine receptor kinase B and p75), and epigenetic regulations, including the activity of HATs and HADCs in the hippocampus. We used the senescence-accelerated mouse (SAM) model, specifically 13-month-old SAM resistant 1(SAMR1) and SAM prone 1 (SAMP1) lines. Mice were distributed into four groups based on accelerated senescence and exercise status. Mice in the exercise groups exercised on a treadmill for approximately 60min a day, 5days a week. Aerobic exercise for 4 weeks improved cognitive function, accompanied by an increase in BDNF expression and a decrease in p75 transcription in both SAMR1 and SAMP1. In addition, the exercise regimen activated both HAT and HDAC in the hippocampus. Therefore, the present study reveals that despite accelerated senescence, long-term exercise improved cognitive function, upregulated the expression of BDNF, and downregulated p75, a receptor involved in apoptotic signaling. Furthermore, long-term exercise enhanced activity of both HAT and HDAC, which may contribute to the transcriptional regulation underlying the improvement of cognitive function. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Occurrence of human bocaviruses and parvovirus 4 in solid tissues.

    Science.gov (United States)

    Norja, Päivi; Hedman, Lea; Kantola, Kalle; Kemppainen, Kaisa; Suvilehto, Jari; Pitkäranta, Anne; Aaltonen, Leena-Maija; Seppänen, Mikko; Hedman, Klaus; Söderlund-Venermo, Maria

    2012-08-01

    Human bocaviruses 1-4 (HBoV1-4) and parvovirus 4 (PARV4) are recently discovered human parvoviruses. HBoV1 is associated with respiratory infections of young children, while HBoV2-4 are enteric viruses. The clinical manifestations of PARV4 remain unknown. The objective of this study was to determine whether the DNAs of HBoV1-4 and PARV4 persist in human tissues long after primary infection. Biopsies of tonsillar tissue, skin, and synovia were examined for HBoV1-4 DNA and PARV4 DNA by PCR. Serum samples from the tissue donors were assayed for HBoV1 and PARV4 IgG and IgM antibodies. To obtain species-specific seroprevalences for HBoV1 and for HBoV2/3 combined, the sera were analyzed after virus-like particle (VLP) competition. While HBoV1 DNA was detected exclusively in the tonsillar tissues of 16/438 individuals (3.7%), all of them ≤8 years of age. HBoV2-4 and PARV4 DNAs were absent from all tissue types. HBoV1 IgG seroprevalence was 94.9%. No subject had HBoV1 or PARV4 IgM, nor did they have PARV4 IgG. The results indicate that HBoV1 DNA occurred in a small proportion of tonsils of young children after recent primary HBoV1 infection, but did not persist long in the other tissue types studied, unlike parvovirus B19 DNA. The results obtained by the PARV4 assays are in line with previous results on PARV4 epidemiology. Copyright © 2012 Wiley Periodicals, Inc.

  17. The histone acetyltransferase PsGcn5 mediates oxidative stress responses and is required for full virulence of Phytophthora sojae.

    Science.gov (United States)

    Zhao, Wei; Wang, Tao; Liu, Shusen; Chen, Qingqing; Qi, Rende

    2015-10-01

    In eukaryotic organisms, histone acetyltransferase complexes are coactivators that are important for transcriptional activation by modifying chromatin. In this study, a gene (PsGcn5) from Phytophthora sojae encoding a histone acetyltransferase was identified as a homolog of one component of the histone acetyltransferase complex from yeasts to mammals. PsGcn5 was constitutively expressed in each stage tested, but had a slightly higher expression in sporulating hyphae and 3 h after infection. PsGcn5-silenced mutants were generated using polyethylene glycol-mediated protoplast stable transformation. These mutants had normal development, but compared to wild type strains they had higher sensitivity to hydrogen peroxide (H2O2) and significantly reduced virulence in soybean. Diaminobenzidine staining revealed an accumulation of H2O2 around the infection sites of PsGcn5-silenced mutants but not for wild type strains. Inhibition of the plant NADPH oxidase by diphenyleneiodonium prevented host-derived H2O2 accumulation in soybean cells and restored infectious hyphal growth of the mutants. Thus, we concluded that PsGcn5 is important for growth under conditions of oxidative stress and contributes to the full virulence of P. sojae by suppressing the host-derived reactive oxygen species. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Characterization of N-acetyltransferase 1 and 2 polymorphisms and haplotype analysis for inflammatory bowel disease and sporadic colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Cobbs Gary A

    2007-05-01

    Full Text Available Abstract Background N-acetyltransferase 1 (NAT1 and 2 (NAT2 are polymorphic isoenzymes responsible for the metabolism of numerous drugs and carcinogens. Acetylation catalyzed by NAT1 and NAT2 are important in metabolic activation of arylamines to electrophilic intermediates that initiate carcinogenesis. Inflammatory bowel diseases (IBD consist of Crohn's disease (CD and ulcerative colitis (UC, both are associated with increased colorectal cancer (CRC risk. We hypothesized that NAT1 and/or NAT2 polymorphisms contribute to the increased cancer evident in IBD. Methods A case control study was performed with 729 Caucasian participants, 123 CRC, 201 CD, 167 UC, 15 IBD dysplasia/cancer and 223 controls. NAT1 and NAT2 genotyping were performed using Taqman based techniques. Eight single nucleotide polymorphisms (SNPs were characterized for NAT1 and 7 SNPs for NAT2. Haplotype frequencies were estimated using an Expectation-Maximization (EM method. Disease groups were compared to a control group for the frequencies at each individual SNP separately. The same groups were compared for the frequencies of NAT1 and NAT2 haplotypes and deduced NAT2 phenotypes. Results No statistically significant differences were found for any comparison. Strong linkage disequilibrium was present among both the NAT1 SNPs and the NAT2 SNPs. Conclusion This study did not demonstrate an association between NAT1 and NAT2 polymorphisms and IBD or sporadic CRC, although power calculations indicate this study had sufficient sample size to detect differences in frequency as small as 0.05 to 0.15 depending on SNP or haplotype.

  19. IL-1β-specific recruitment of GCN5 histone acetyltransferase induces the release of PAF1 from chromatin for the de-repression of inflammatory response genes.

    Science.gov (United States)

    Kim, Nari; Sun, Hwa-Young; Youn, Min-Young; Yoo, Joo-Yeon

    2013-04-01

    To determine the functional specificity of inflammation, it is critical to orchestrate the timely activation and repression of inflammatory responses. Here, we explored the PAF1 (RNA polymerase II associated factor)-mediated signal- and locus-specific repression of genes induced through the pro-inflammatory cytokine interleukin (IL)-1β. Using microarray analysis, we identified the PAF1 target genes whose expression was further enhanced by PAF1 knockdown in IL-1β-stimulated HepG2 hepatocarcinomas. PAF1 bound near the transcription start sites of target genes and dissociated on stimulation. In PAF1-deficient cells, more elongating RNA polymerase II and acetylated histones were observed, although IL-1β-mediated activation and recruitment of nuclear factor κB (NF-κB) were not altered. Under basal conditions, PAF1 blocked histone acetyltransferase general control non-depressible 5 (GCN5)-mediated acetylation on H3K9 and H4K5 residues. On IL-1β stimulation, activated GCN5 discharged PAF1 from chromatin, allowing productive transcription to occur. PAF1 bound to histones but not to acetylated histones, and the chromatin-binding domain of PAF1 was essential for target gene repression. Moreover, IL-1β-induced cell migration was similarly controlled through counteraction between PAF1 and GCN5. These results suggest that the IL-1β signal-specific exchange of PAF1 and GCN5 on the target locus limits inappropriate gene induction and facilitates the timely activation of inflammatory responses.

  20. The HAT Score-A Simple Risk Stratification Score for Coagulopathic Bleeding During Adult Extracorporeal Membrane Oxygenation.

    Science.gov (United States)

    Lonergan, Terence; Herr, Daniel; Kon, Zachary; Menaker, Jay; Rector, Raymond; Tanaka, Kenichi; Mazzeffi, Michael

    2017-06-01

    The study objective was to create an adult extracorporeal membrane oxygenation (ECMO) coagulopathic bleeding risk score. Secondary analysis was performed on an existing retrospective cohort. Pre-ECMO variables were tested for association with coagulopathic bleeding, and those with the strongest association were included in a multivariable model. Using this model, a risk stratification score was created. The score's utility was validated by comparing bleeding and transfusion rates between score levels. Bleeding also was examined after stratifying by nadir platelet count and overanticoagulation. Predictive power of the score was compared against the risk score for major bleeding during anti-coagulation for atrial fibrillation (HAS-BLED). Tertiary care academic medical center. The study comprised patients who received venoarterial or venovenous ECMO over a 3-year period, excluding those with an identified source of surgical bleeding during exploration. None. Fifty-three (47.3%) of 112 patients experienced coagulopathic bleeding. A 3-variable score-hypertension, age greater than 65, and ECMO type (HAT)-had fair predictive value (area under the receiver operating characteristic curve [AUC] = 0.66) and was superior to HAS-BLED (AUC = 0.64). As the HAT score increased from 0 to 3, bleeding rates also increased as follows: 30.8%, 48.7%, 63.0%, and 71.4%, respectively. Platelet and fresh frozen plasma transfusion tended to increase with the HAT score, but red blood cell transfusion did not. Nadir platelet count less than 50×10 3 /µL and overanticoagulation during ECMO increased the AUC for the model to 0.73, suggesting additive risk. The HAT score may allow for bleeding risk stratification in adult ECMO patients. Future studies in larger cohorts are necessary to confirm these findings. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Bridging Theory and Experiment to Address Structural Properties of Truncated Haemoglobins: Insights from Thermobifida fusca HbO.

    Science.gov (United States)

    Howes, Barry D; Boechi, Leonardo; Boffi, Alberto; Estrin, Dario E; Smulevich, Giulietta

    2015-01-01

    In this chapter, we will discuss the paradigmatic case of Thermobifida fusca (Tf-trHb) HbO in its ferrous and ferric states and its behaviour towards a battery of possible ligands. This choice was dictated by the fact that it has been one of the most extensively studied truncated haemoglobins, both in terms of spectroscopic and molecular dynamics studies. Tf-trHb typifies the structural properties of group II trHbs, as the active site is characterized by a highly polar distal environment in which TrpG8, TyrCD1, and TyrB10 provide three potential H-bond donors in the distal cavity capable of stabilizing the incoming ligands. The role of these residues in key topological positions, and their interplay with the iron-bound ligands, has been addressed in studies carried out on the CO, F(-), OH(-), CN(-), and HS(-) adducts formed with the wild-type protein and a combinatorial set of mutants, in which the distal polar residues, TrpG8, TyrCD1, and TyrB10, have been singly, doubly, or triply replaced by a Phe residue. In this context, such a complete analysis provides an excellent benchmark for the investigation of the relationship between protein structure and function, allowing one to translate physicochemical properties of the active site into the observed functional behaviour. Tf-trHb will be compared with other members of the group II trHbs and, more generally, with members of the other trHb subgroups. © 2015 Elsevier Ltd. All rights reserved.

  2. Effect of dietary γ-aminobutyric acid on the nerve growth factor and the choline acetyltransferase in the cerebral cortex and hippocampus of ovariectomized female rats.

    Science.gov (United States)

    Tujioka, Kazuyo; Thanapreedawat, Panicha; Yamada, Takashi; Yokogoshi, Hidehiko; Horie, Kenji; Kim, Mujo; Tsutsui, Kazumi; Hayase, Kazutoshi

    2014-01-01

    The brain protein synthesis and the plasma concentration of growth hormone (GH) is sensitive to the dietary γ-aminobutyric acid (GABA) in ovariectomized female rats; however, the role of dietary GABA on biomarkers including nerve growth factor (NGF) and choline acetyltransferase for the function of cholinergic neurons remains unknown in ovariectomized female rats. The purpose of this study was to determine whether the dietary GABA affects the concentration and mRNA level of NGF, and the activity of choline acetyltransferase in the brains of ovariectomized female rats. Experiments were done on two groups of 24-wk-old ovariectomized female rats given 0 or 0.5% GABA added to a 20% casein diet. The concentrations of NGF and activities of choline acetyltransferase in the cerebral cortex and hippocampus, and mRNA level of NGF in the hippocampus increased significantly with the 20% casein+0.5% GABA compared with the 20% casein diet alone. In the hippocampus, the mRNA level of NGF significantly correlated with the NGF concentration (r=0.714, pGABA to ovariectomized female rats is likely to control the mRNA level and concentration of NGF and cause an increase in the activity of choline acetyltransferase in the brains.

  3. HAT-P-12b: A LOW-DENSITY SUB-SATURN MASS PLANET TRANSITING A METAL-POOR K DWARF

    International Nuclear Information System (INIS)

    Hartman, J. D.; Bakos, G. A.; Torres, G.; Noyes, R. W.; Pal, A.; Latham, D. W.; Sipocz, B.; Esquerdo, G. A.; Sasselov, D. D.; Kovacs, Gabor; Stefanik, R. P.; Fernandez, J. M.; Kovacs, Geza; Fischer, D. A.; Johnson, J. A.; Marcy, G. W.; Howard, A. W.; Butler, R. P.; Lazar, J.; Papp, I.

    2009-01-01

    We report on the discovery of HAT-P-12b, a transiting extrasolar planet orbiting the moderately bright V ∼ 12.8 K4 dwarf GSC 03033 - 00706, with a period P = 3.2130598 ± 0.0000021 d, transit epoch T c = 2454419.19556 ± 0.00020 (BJD), and transit duration 0.0974 ± 0.0006 d. The host star has a mass of 0.73 ± 0.02 M sun , radius of 0.70 +0.02 -0.01 R sun , effective temperature 4650 ± 60 K, and metallicity [Fe/H] = -0.29 ± 0.05. We find a slight correlation between the observed spectral line bisector spans and the radial velocity, so we consider, and rule out, various blend configurations including a blend with a background eclipsing binary, and hierarchical triple systems where the eclipsing body is a star or a planet. We conclude that a model consisting of a single star with a transiting planet best fits the observations, and show that a likely explanation for the apparent correlation is contamination from scattered moonlight. Based on this model, the planetary companion has a mass of 0.211 ± 0.012 M J and radius of 0.959 +0.029 -0.021 R J yielding a mean density of 0.295 ± 0.025 g cm -3 . Comparing these observations with recent theoretical models, we find that HAT-P-12b is consistent with a ∼1-4.5 Gyr, mildly irradiated, H/He-dominated planet with a core mass M C ∼ + . HAT-P-12b is thus the least massive H/He-dominated gas giant planet found to date. This record was previously held by Saturn.

  4. Arylamine N-acetyltransferase 1 in situ N-acetylation on CD3+ peripheral blood mononuclear cells correlate with NATb mRNA and NAT1 haplotype.

    Science.gov (United States)

    Salazar-González, Raúl A; Turiján-Espinoza, Eneida; Hein, David W; Niño-Moreno, Perla C; Romano-Moreno, Silvia; Milán-Segovia, Rosa C; Portales-Pérez, Diana P

    2018-02-01

    Human arylamine N-acetyltransferase 1 (NAT1) is responsible for the activation and elimination of xenobiotic compounds and carcinogens. Genetic polymorphisms in NAT1 modify both drug efficacy and toxicity. Previous studies have suggested a role for NAT1 in the development of several diseases. The aim of the present study was to evaluate NAT1 protein expression and in situ N-acetylation capacity in peripheral blood mononuclear cells (PBMC), as well as their possible associations with the expression of NAT1 transcript and NAT1 genotype. We report NAT1 protein, mRNA levels, and N-acetylation in situ activity for PBMC obtained from healthy donors. NAT1-specific protein expression was higher in CD3+ cells than other major immune cell subtypes (CD19 or CD56 cells). N-acetylation of pABA varied markedly among the PBMC of participants, but correlated very significantly with levels of NAT1 transcripts. NAT1*4 subjects showed significantly (p = 0.017) higher apparent pABA V max of 71.3 ± 3.7 versus the NAT1*14B subjects apparent V max of 58.5 ± 2.5 nmoles Ac-pABA/24 h/million cells. Levels of pABA N-acetylation activity at each concentration of substrate evaluated also significantly correlated with NAT1 mRNA levels for all samples (p N-acetylation in PBMC is higher in T cell than in other immune cell subtypes and that individual variation in N-acetylation capacity is dependent upon NAT1 mRNA and NAT1 haplotype.

  5. LHX3 interacts with inhibitor of histone acetyltransferase complex subunits LANP and TAF-1β to modulate pituitary gene regulation.

    Science.gov (United States)

    Hunter, Chad S; Malik, Raleigh E; Witzmann, Frank A; Rhodes, Simon J

    2013-01-01

    LIM-homeodomain 3 (LHX3) is a transcription factor required for mammalian pituitary gland and nervous system development. Human patients and animal models with LHX3 gene mutations present with severe pediatric syndromes that feature hormone deficiencies and symptoms associated with nervous system dysfunction. The carboxyl terminus of the LHX3 protein is required for pituitary gene regulation, but the mechanism by which this domain operates is unknown. In order to better understand LHX3-dependent pituitary hormone gene transcription, we used biochemical and mass spectrometry approaches to identify and characterize proteins that interact with the LHX3 carboxyl terminus. This approach identified the LANP/pp32 and TAF-1β/SET proteins, which are components of the inhibitor of histone acetyltransferase (INHAT) multi-subunit complex that serves as a multifunctional repressor to inhibit histone acetylation and modulate chromatin structure. The protein domains of LANP and TAF-1β that interact with LHX3 were mapped using biochemical techniques. Chromatin immunoprecipitation experiments demonstrated that LANP and TAF-1β are associated with LHX3 target genes in pituitary cells, and experimental alterations of LANP and TAF-1β levels affected LHX3-mediated pituitary gene regulation. Together, these data suggest that transcriptional regulation of pituitary genes by LHX3 involves regulated interactions with the INHAT complex.

  6. Immunolocalization of choline acetyltransferase of common type in the central brain mass of Octopus vulgaris

    Directory of Open Access Journals (Sweden)

    A. Casini

    2012-07-01

    Full Text Available Acetylcholine, the first neurotransmitter to be identified in the vertebrate frog, is widely distributed among the animal kingdom. The presence of a large amount of acetylcholine in the nervous system of cephalopods is well known from several biochemical and physiological studies. However, little is known about the precise distribution of cholinergic structures due to a lack of a suitable histochemical technique for detecting acetylcholine. The most reliable method to visualize the cholinergic neurons is the immunohistochemical localization of the enzyme choline acetyltransferase, the synthetic enzyme of acetylcholine. Following our previous study on the distribution patterns of cholinergic neurons in the Octopus vulgaris visual system, using a novel antibody that recognizes choline acetyltransferase of the common type (cChAT, now we extend our investigation on the octopus central brain mass. When applied on sections of octopus central ganglia, immunoreactivity for cChAT was detected in cell bodies of all central brain mass lobes with the notable exception of the subfrontal and subvertical lobes. Positive varicosed nerves fibers where observed in the neuropil of all central brain mass lobes.

  7. Immunolocalization of choline acetyltransferase of common type in the central brain mass of Octopus vulgaris.

    Science.gov (United States)

    Casini, A; Vaccaro, R; D'Este, L; Sakaue, Y; Bellier, J P; Kimura, H; Renda, T G

    2012-07-19

    Acetylcholine, the first neurotransmitter to be identified in the vertebrate frog, is widely distributed among the animal kingdom. The presence of a large amount of acetylcholine in the nervous system of cephalopods is well known from several biochemical and physiological studies. However, little is known about the precise distribution of cholinergic structures due to a lack of a suitable histochemical technique for detecting acetylcholine. The most reliable method to visualize the cholinergic neurons is the immunohistochemical localization of the enzyme choline acetyltransferase, the synthetic enzyme of acetylcholine. Following our previous study on the distribution patterns of cholinergic neurons in the Octopus vulgaris visual system, using a novel antibody that recognizes choline acetyltransferase of the common type (cChAT), now we extend our investigation on the octopus central brain mass. When applied on sections of octopus central ganglia, immunoreactivity for cChAT was detected in cell bodies of all central brain mass lobes with the notable exception of the subfrontal and subvertical lobes. Positive varicosed nerves fibers where observed in the neuropil of all central brain mass lobes.

  8. Human bocavirus in children with acute respiratory infections in Vietnam.

    Science.gov (United States)

    Tran, Dinh Nguyen; Nguyen, Tran Quynh Nhu; Nguyen, Tuan Anh; Hayakawa, Satoshi; Mizuguchi, Masashi; Ushijima, Hiroshi

    2014-06-01

    Acute respiratory infections are the major cause of morbidity and mortality globally. Human bocavirus (HBoV), a novel virus, is recognized to increasingly associate with previously unknown etiology respiratory infections in young children. In this study, the epidemiological, clinical, and molecular characteristics of HBoV infections were described in hospitalized Vietnamese pediatric patients. From April 2010 to May 2011, 1,082 nasopharyngeal swab samples were obtained from patients with acute respiratory infections at the Children's Hospital 2, Ho Chi Minh City, Vietnam. Samples were screened for HBoV by PCR and further molecularly characterized by sequencing. HBoV was found in 78 (7.2%) children. Co-infection with other viruses was observed in 66.7% of patients infected with HBoV. Children 12-24 months old were the most affected age group. Infections with HBoV were found year-round, though most cases occurred in the dry season (December-April). HBoV was possible to cause severe diseases as determined by higher rates of hypoxia, pneumonia, and longer hospitalization duration in patients with HBoV infection than in those without (P-value infection with HBoV did not affect the disease severity. The phylogenetic analysis of partial VP1 gene showed minor variations and all HBoV sequences belonged to species 1 (HBoV1). In conclusion, HBoV1 was circulating in Vietnam and detected frequently in young children during dry season. Acute respiratory infections caused by HBoV1 were severe enough for hospitalization, which implied that HBoV1 may have an important role in acute respiratory infections among children. © 2013 Wiley Periodicals, Inc.

  9. The boson and the Mexican hat

    International Nuclear Information System (INIS)

    Cohen-Tannoudji, Gilles; Spiro, Michel

    2013-01-01

    This document contains a brief presentation and the table of contents of a book in which the authors who reports the evolutions of the contemporary astrophysics theories, and the scientific, technological and human adventure of the CERN until the discovery of the Higgs boson by means of the LHC. The Mexican hat is the name given to the mechanism by which the boson reports the origin of the elementary particle masses. The first part reports the boson genealogy: the law of universal gravitation, the relativity and the limits of the rational mechanics, quantum mechanics, and particle physics at the end of the 1960's. The second part addresses the necessary existence of the boson: quantum electrodynamics, from the quark model to quantum chromo-dynamics, from intermediate bosons to the Brout, Englert and Higgs boson, the standard cosmology model. The third part deals with the perspectives opened by the existence and evidence of the boson: the search for physics theory and models beyond standard models

  10. Overexpression of rice serotonin N-acetyltransferase 1 in transgenic rice plants confers resistance to cadmium and senescence and increases grain yield.

    Science.gov (United States)

    Lee, Kyungjin; Back, Kyoungwhan

    2017-04-01

    While ectopic overexpression of serotonin N-acetyltransferase (SNAT) in plants has been accomplished using animal SNAT genes, ectopic overexpression of plant SNAT genes in plants has not been investigated. Because the plant SNAT protein differs from that of animals in its subcellular localization and enzyme kinetics, its ectopic overexpression in plants would be expected to give outcomes distinct from those observed from overexpression of animal SNAT genes in transgenic plants. Consistent with our expectations, we found that transgenic rice plants overexpressing rice (Oryza sativa) SNAT1 (OsSNAT1) did not show enhanced seedling growth like that observed in ovine SNAT-overexpressing transgenic rice plants, although both types of plants exhibited increased melatonin levels. OsSNAT1-overexpressing rice plants did show significant resistance to cadmium and senescence stresses relative to wild-type controls. In contrast to tomato, melatonin synthesis in rice seedlings was not induced by selenium and OsSNAT1 transgenic rice plants did not show tolerance to selenium. T 2 homozygous OsSNAT1 transgenic rice plants exhibited increased grain yield due to increased panicle number per plant under paddy field conditions. These benefits conferred by ectopic overexpression of OsSNAT1 had not been observed in transgenic rice plants overexpressing ovine SNAT, suggesting that plant SNAT functions differently from animal SNAT in plants. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Genetic disruption of tubulin acetyltransferase, αTAT1, inhibits proliferation and invasion of colon cancer cells through decreases in Wnt1/β-catenin signaling

    International Nuclear Information System (INIS)

    Oh, Somi; You, Eunae; Ko, Panseon; Jeong, Jangho; Keum, Seula; Rhee, Sangmyung

    2017-01-01

    Microtubules are required for diverse cellular processes, and abnormal regulation of microtubule dynamics is closely associated with severe diseases including malignant tumors. In this study, we report that α-tubulin N-acetyltransferase (αTAT1), a regulator of α-tubulin acetylation, is required for colon cancer proliferation and invasion via regulation of Wnt1 and its downstream genes expression. Public transcriptome analysis showed that expression of ATAT1 is specifically upregulated in colon cancer tissue. A knockout (KO) of ATAT1 in the HCT116 colon cancer cell line, using the CRISPR/Cas9 system showed profound inhibition of proliferative and invasive activities of these cancer cells. Overexpression of αTAT1 or the acetyl-mimic K40Q α-tubulin mutant in αTAT1 KO cells restored the invasiveness, indicating that microtubule acetylation induced by αTAT1 is critical for HCT116 cell invasion. Analysis of colon cancer-related gene expression in αTAT1 KO cells revealed that the loss of αTAT1 decreased the expression of WNT1. Mechanistically, abrogation of tubulin acetylation by αTAT1 knockout inhibited localization of β-catenin to the plasma membrane and nucleus, thereby resulting in the downregulation of Wnt1 and of its downstream genes including CCND1, MMP-2, and MMP-9. These results suggest that αTAT1-mediated Wnt1 expression via microtubule acetylation is important for colon cancer progression. - Highlights: • Ablation of αTAT1 inhibits HCT116 colon cancer cell invasion. • αTAT1/acetylated microtubules regulate expression of Wnt1/β-catenin target genes. • Acetylated microtubules regulate cellular localization of β-catenin. • Loss of αTAT1 prevents Wnt1 from inducing β-catenin-dependent and -independent pathways.

  12. Gene expression in tumor cells and stroma in dsRed 4T1 tumors in eGFP-expressing mice with and without enhanced oxygenation

    International Nuclear Information System (INIS)

    Moen, Ingrid; Øyan, Anne M; Stuhr, Linda EB; Jevne, Charlotte; Wang, Jian; Kalland, Karl-Henning; Chekenya, Martha; Akslen, Lars A; Sleire, Linda; Enger, Per Ø; Reed, Rolf K

    2012-01-01

    The tumor microenvironment is pivotal in tumor progression. Thus, we aimed to develop a mammary tumor model to elucidate molecular characteristics in the stroma versus the tumor cell compartment by global gene expression. Secondly, since tumor hypoxia influences several aspects of tumor pathophysiology, we hypothesized that hyperoxia might have an inhibitory effect on tumor growth per se. Finally, we aimed to identify differences in gene expression and key molecular mechanisms, both in the native state and following treatment. 4T1 dsRed breast cancer cells were injected into eGFP expressing NOD/SCID mice. Group 1 was exposed to 3 intermittent HBO treatments (Day 1, 4 and 7), Group 2 to 7 daily HBO treatments (both 2.5bar, 100% O 2 , à 90 min), whereas the controls were exposed to a normal atmosphere. Tumor growth, histology, vascularisation, cell proliferation, cell death and metastasis were assessed. Fluorescence-activated cell sorting was used to separate tumor cells from stromal cells prior to gene expression analysis. The purity of sorted cells was verified by fluorescence microscopy. Gene expression profiling demonstrated that highly expressed genes in the untreated tumor stroma included constituents of the extracellular matrix and matrix metalloproteinases. Tumor growth was significantly inhibited by HBO, and the MAPK pathway was found to be significantly reduced. Immunohistochemistry indicated a significantly reduced microvessel density after intermittent HBO, whereas daily HBO did not show a similar effect. The anti-angiogenic response was reflected in the expression trends of angiogenic factors. The present in vivo mammary tumor model enabled us to separate tumor and stromal cells, and demonstrated that the two compartments are characterized by distinct gene expressions, both in the native state and following HBO treatments. Furthermore, hyperoxia induced a significant tumor growth-inhibitory effect, with significant down-regulation of the MAPK pathway

  13. A method to detect transfected chloramphenicol acetyltransferase gene expression in intact animals

    International Nuclear Information System (INIS)

    Narayanan, R.; Jastreboff, M.M.; Chiu, Chang Fang; Ito, Etsuro; Bertino, J.R.

    1988-01-01

    A rapid procedure is described for assaying chloramphenicol acetyltransferase enzyme activity in intact animals following transfection of the RSV CAT plasmid into mouse bone marrow cells by electroporation. The reconstituted mice were injected with [ 14 C]chloramphenicol and ethyl acetate extracts of 24-h urine samples were analyzed by TLC autoradiography for the excretion of 14 C-labeled metabolites. CAT expression in vivo can be detected by the presence of acetylated 14 C-labeled metabolites in the urine within 1 week after bone marrow transplantation and, under the conditions described, these metabolites can be detected for at least 3 months. CAT expression in intact mice as monitored by the urine assay correlates with the CAT expression in the hematopoietic tissues assayed in vitro. This method offers a quick mode of screening for introduced CAT gene expression in vivo without sacrificing the mice

  14. A Bayesian analysis of HAT-P-7b using the EXONEST algorithm

    International Nuclear Information System (INIS)

    Placek, Ben; Knuth, Kevin H.

    2015-01-01

    The study of exoplanets (planets orbiting other stars) is revolutionizing the way we view our universe. High-precision photometric data provided by the Kepler Space Telescope (Kepler) enables not only the detection of such planets, but also their characterization. This presents a unique opportunity to apply Bayesian methods to better characterize the multitude of previously confirmed exoplanets. This paper focuses on applying the EXONEST algorithm to characterize the transiting short-period-hot-Jupiter, HAT-P-7b (also referred to as Kepler-2b). EXONEST evaluates a suite of exoplanet photometric models by applying Bayesian Model Selection, which is implemented with the MultiNest algorithm. These models take into account planetary effects, such as reflected light and thermal emissions, as well as the effect of the planetary motion on the host star, such as Doppler beaming, or boosting, of light from the reflex motion of the host star, and photometric variations due to the planet-induced ellipsoidal shape of the host star. By calculating model evidences, one can determine which model best describes the observed data, thus identifying which effects dominate the planetary system. Presented are parameter estimates and model evidences for HAT-P-7b

  15. Phase II, Title I engineering assessment of inactive uranium mill tailings, Mexican Hat site, Mexican Hat, Utah

    International Nuclear Information System (INIS)

    1977-01-01

    An engineering assessment of the problems resulting from the existence of radioactive uranium mill tailings at the Mexican Hat millsite in Utah is presented. Topographic maps, data on core drillings and radiometric measurements sufficient to determine areas and volumes of tailings and other radium-contaminated materials, the evaluation of resulting radiation exposures of individuals residing nearby, the investigation of site hydrology and meteorology, and the evaluation and costing of alternative corrective actions are presented. Radon gas release from the 2,200,000 tons of tailings on the site constitutes the most significant environmental impact. T he six alternative actions presented are directed towards restricting access to the site, returning the windblown tailings to the piles and stabilizing the piles with cover material, and consolidating the two piles into one pile and stabilizing it with cover material. Fencing around the site or the tailings and the decontamination of mill buildings is included in all options. Costs of the options range from $370,000 to $4,390,000

  16. Inhibition of histone deacetylation alters Arabidopsis root growth in response to auxin via PIN1 degradation.

    Science.gov (United States)

    Nguyen, Hoai Nguyen; Kim, Jun Hyeok; Jeong, Chan Young; Hong, Suk-Whan; Lee, Hojoung

    2013-10-01

    Our results showed the histone deacetylase inhibitors (HDIs) control root development in Arabidopsis via regulation of PIN1 degradation. Epigenetic regulation plays a crucial role in the expression of many genes in response to exogenous or endogenous signals in plants as well as other organisms. One of epigenetic mechanisms is modifications of histone, such as acetylation and deacetylation, are catalyzed by histone acetyltransferase (HAT) and histone deacetylase (HDAC), respectively. The Arabidopsis HDACs, HDA6, and HDA19, were reported to function in physiological processes, including embryo development, abiotic stress response, and flowering. In this study, we demonstrated that histone deacetylase inhibitors (HDIs) inhibit primary root elongation and lateral root emergence. In response to HDIs treatment, the PIN1 protein was almost abolished in the root tip. However, the PIN1 gene did not show decreased expression in the presence of HDIs, whereas IAA genes exhibited increases in transcript levels. In contrast, we observed a stable level of gene expression of stress markers (KIN1 and COR15A) and a cell division marker (CYCB1). Taken together, these results suggest that epigenetic regulation may control auxin-mediated root development through the 26S proteasome-mediated degradation of PIN1 protein.

  17. Conserved B-cell epitopes among human bocavirus species indicate potential diagnostic targets.

    Directory of Open Access Journals (Sweden)

    Zhuo Zhou

    Full Text Available BACKGROUND: Human bocavirus species 1-4 (HBoV1-4 have been associated with respiratory and enteric infections in children. However, the immunological mechanisms in response to HBoV infections are not fully understood. Though previous studies have shown cross-reactivities between HBoV species, the epitopes responsible for this phenomenon remain unknown. In this study, we used genomic and immunologic approaches to identify the reactive epitopes conserved across multiple HBoV species and explored their potential as the basis of a novel diagnostic test for HBoVs. METHODOLOGY/PRINCIPAL FINDINGS: We generated HBoV1-3 VP2 gene fragment phage display libraries (GFPDLs and used these libraries to analyze mouse antisera against VP2 protein of HBoV1, 2, and 3, and human sera positive for HBoVs. Using this approach, we mapped four epitope clusters of HBoVs and identified two immunodominant peptides--P1 (¹MSDTDIQDQQPDTVDAPQNT²⁰, and P2 (¹⁶²EHAYPNASHPWDEDVMPDL¹⁸⁰--that are conserved among HBoV1-4. To confirm epitope immunogenicity, we immunized mice with the immunodominant P1 and P2 peptides identified in our screen and found that they elicited high titer antibodies in mice. These two antibodies could only recognize the VP2 of HBoV 1-4 in Western blot assays, rather than those of the two other parvoviruses human parvovirus B19 and human parvovirus 4 (PARV4. Based on our findings, we evaluated epitope-based peptide-IgM ELISAs as potential diagnostic tools for HBoVs IgM antibodies. We found that the P1+P2-IgM ELISA showed a higher sensitivity and specificity in HBoVs IgM detection than the assays using a single peptide. CONCLUSIONS/SIGNIFICANCE: The identification of the conserved B-cell epitopes among human bocavirus species contributes to our understanding of immunological cross-reactivities of HBoVs, and provides important insights for the development of HBoV diagnostic tools.

  18. The TopHat experiment: A balloon-borne instrument for mapping millimeter and submillimeter emission

    DEFF Research Database (Denmark)

    Silverberg, R.F.; Cheng, E.S.; Aguirre, J.E.

    2005-01-01

    The TopHat experiment was designed to measure the anisotropy in the cosmic microwave background radiation on angular scales from 0.degrees 3 to 30 degrees and the thermal emission from both Galactic and extragalactic dust. The balloon-borne instrument had five spectral bands spanning frequencies ...

  19. The G-HAT Search for Advanced Extraterrestrial Civilizations: The Reddest Extended WISE Sources

    Science.gov (United States)

    Maldonado, Jessica; Povich, Matthew S.; Wright, Jason; Griffith, Roger; Sigurdsson, Steinn; Mullan, Brendan L.

    2015-01-01

    Freeman Dyson (1960) theorized how to identify possible signatures of advanced extra-terrestrial civilizations by their waste heat, an inevitable byproduct of a civilization using a significant fraction of the luminosity from their host star. If a civilizations could tap the starlight throughout their host galaxy their waste heat would be easily detectable by recent infrared surveys. The Glimpsing Heat from Alien Technologies (G-HAT) pilot project aims to place limits on the existence of extraterrestrial civilizations at pan-galactic scales. We present results from the G-HAT cleaned catalog of 563 extremely red, extended high Galactic latitude (|b| ≥ 10) sources from the WISE All-Sky Catalog. Our catalog includes sources new to the scientific literature along with well-studied objects (e.g. starburst galaxies, AGN, and planetary nebulae) that exemplify extreme WISE colors. Objects of particular interest include a supergiant Be star (48 Librae) surrounded by a resolved, mid-infrared nebula, possibly indicating dust in the stellar wind ejecta, and a curious cluster of seven extremely red WISE sources (associated with IRAS 04287+6444) that have no optical counterparts.

  20. Antioxidant N-acetyltransferase Mpr1/2 of industrial baker's yeast enhances fermentation ability after air-drying stress in bread dough.

    Science.gov (United States)

    Sasano, Yu; Takahashi, Shunsuke; Shima, Jun; Takagi, Hiroshi

    2010-03-31

    During bread-making processes, yeast cells are exposed to multiple stresses. Air-drying stress is one of the most harmful stresses by generation of reactive oxygen species (ROS). Previously, we discovered that the novel N-acetyltransferase Mpr1/2 confers oxidative stress tolerance by reducing intracellular ROS level in Saccharomyces cerevisiae Sigma1278b strain. In this study, we revealed that Japanese industrial baker's yeast possesses one MPR gene. The nucleotide sequence of the MPR gene in industrial baker's yeast was identical to the MPR2 gene in Sigma1278b strain. Gene disruption analysis showed that the MPR2 gene in industrial baker's yeast is involved in air-drying stress tolerance by reducing the intracellular oxidation levels. We also found that expression of the Lys63Arg and Phe65Leu variants with enhanced enzymatic activity and stability, respectively, increased the fermentation ability of bread dough after exposure to air-drying stress compared with the wild-type Mpr1. In addition, our recent study showed that industrial baker's yeast cells accumulating proline exhibited enhanced freeze tolerance in bread dough. Proline accumulation also enhanced the fermentation ability after air-drying stress treatment in industrial baker's yeast. Hence, the antioxidant enzyme Mpr1/2 could be promising for breeding novel yeast strains that are tolerant to air-drying stress. Copyright 2010 Elsevier B.V. All rights reserved.

  1. Acetyl coenzyme A synthetase is acetylated on multiple lysine residues by a protein acetyltransferase with a single Gcn5-type N-acetyltransferase (GNAT) domain in Saccharopolyspora erythraea.

    Science.gov (United States)

    You, Di; Yao, Li-Li; Huang, Dan; Escalante-Semerena, Jorge C; Ye, Bang-Ce

    2014-09-01

    Reversible lysine acetylation (RLA) is used by cells of all domains of life to modulate protein function. To date, bacterial acetylation/deacetylation systems have been studied in a few bacteria (e.g., Salmonella enterica, Bacillus subtilis, Escherichia coli, Erwinia amylovora, Mycobacterium tuberculosis, and Geobacillus kaustophilus), but little is known about RLA in antibiotic-producing actinomycetes. Here, we identify the Gcn5-like protein acetyltransferase AcuA of Saccharopolyspora erythraea (SacAcuA, SACE_5148) as the enzyme responsible for the acetylation of the AMP-forming acetyl coenzyme A synthetase (SacAcsA, SACE_2375). Acetylated SacAcsA was deacetylated by a sirtuin-type NAD(+)-dependent consuming deacetylase (SacSrtN, SACE_3798). In vitro acetylation/deacetylation of SacAcsA enzyme was studied by Western blotting, and acetylation of lysine residues Lys(237), Lys(380), Lys(611), and Lys(628) was confirmed by mass spectrometry. In a strain devoid of SacAcuA, none of the above-mentioned Lys residues of SacAcsA was acetylated. To our knowledge, the ability of SacAcuA to acetylate multiple Lys residues is unique among AcuA-type acetyltransferases. Results from site-specific mutagenesis experiments showed that the activity of SacAcsA was controlled by lysine acetylation. Lastly, immunoprecipitation data showed that in vivo acetylation of SacAcsA was influenced by glucose and acetate availability. These results suggested that reversible acetylation may also be a conserved regulatory posttranslational modification strategy in antibiotic-producing actinomycetes. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  2. Application of a new adsorbent for fluoride removal from aqueous solutions

    International Nuclear Information System (INIS)

    Srivastav, Arun Lal; Singh, Prabhat K.; Srivastava, Varsha; Sharma, Yogesh C.

    2013-01-01

    Highlights: • A new adsorbent has been prepared. • The adsorbent is non-toxic and easy to synthesize. • HBO 1 has displayed best capacity for the removal of fluoride. • Unlike most adsorbents, HBO 1 is suitable for the removal of fluoride from water. • The process of removal has been optimized. -- Abstract: Hydrous bismuth oxides (HBOs) have been investigated as a possible adsorbent for fluoride removal from water. Apart from bismuth trioxide (Bi 2 O 3 ) compound, three additional HBOs, named as HBO 1 , HBO 2 , and HBO 3 were synthesized in the laboratory and examined for their relative potentials for fluoride removal from aqueous solutions. HBO 1 was observed to have highest fluoride removal at 10 mg/L initial concentration in aqueous environment. Among competitive anions, sulfate and chloride affect the fluoride removal by HBO 1 more adversely than bicarbonate. Characterization of HBOs using X-ray diffraction (XRD) pattern analyses indicated crystalline structures, and the broad chemical composition of materials showed successive increase of Bi(OH) 3 from HBO 1 to HBO 3 , with decrease of BiOCl in the same order. Fourier Transform Infrared (FTIR) spectroscopy analyses indicated presence of Bi-O bond and successively increasing number of peaks corresponding to OH ion from HBO 1 to HBO 3 . Scanning Electron Microscopic (SEM) images of HBOs show rough and porous structure of the materials. Presence of higher proportion of chloride compound in HBO 1 with respect to others appears to be the factor responsible for its better performance in fluoride removal from aqueous solutions

  3. Human bocavirus isolated from children with acute respiratory tract infections in Korea, 2010-2011.

    Science.gov (United States)

    Ahn, Jong Gyun; Choi, Seong Yeol; Kim, Dong Soo; Kim, Ki Hwan

    2014-12-01

    Human bocavirus (HBoV) was first recognized in respiratory samples in 2005. The clinical importance of HBoV infection remains unclear. This report describes the clinical features and molecular phylogeny of HBoV isolates in children with acute respiratory infections. Nasopharyngeal aspirates were obtained from 1,528 children with acute respiratory infections between 2010 and 2011. Respiratory samples were screened for HBoV by multiplex PCR. A phylogenetic analysis of the HBoV VP1/VP2 gene was also undertaken. HBoV was detected in 187 (12.2%) of the 1,528 patients with a peak incidence of infection observed in patients aged 12-24 months. Coinfection with other respiratory viruses was observed in 107 (57.2%) of the HBoV-positive children. The peak of HBoV activity occurred during the month of June in both 2010 and 2011. A higher previous history of wheezing (P = 0.016), a higher frequency of chest retraction (P respiratory symptom score (P = 0.002), and a longer duration of hospital stay (P = 0.021) were observed in HBoV-positive children compared with the HBoV-negative group. Phylogenetic analysis showed all 187 HBoV-positive isolates were identified as HBoV 1, indicating minimal sequence variations among the isolates. A single lineage of HBoV 1 was found to have circulated in children with acute respiratory infections between 2010 and 2011 and was associated with several clinical characteristics including age, seasonality, and clinical severity with retraction, wheezing, and longer hospitalization. The clinical relevance of the minimal sequence variations of HBoV remains to be determined. © 2014 Wiley Periodicals, Inc.

  4. Validation of buoyancy driven spectral tensor model using HATS data

    DEFF Research Database (Denmark)

    Chougule, A.; Mann, Jakob; Kelly, Mark C.

    2016-01-01

    We present a homogeneous spectral tensor model for wind velocity and temperature fluctuations, driven by mean vertical shear and mean temperature gradient. Results from the model, including one-dimensional velocity and temperature spectra and the associated co-spectra, are shown in this paper....... The model also reproduces two-point statistics, such as coherence and phases, via cross-spectra between two points separated in space. Model results are compared with observations from the Horizontal Array Turbulence Study (HATS) field program (Horst et al. 2004). The spectral velocity tensor in the model...

  5. Molecular Evolution of Aralkylamine N-Acetyltransferase in Fish: A Genomic Survey

    Directory of Open Access Journals (Sweden)

    Jia Li

    2015-12-01

    Full Text Available All living organisms synchronize biological functions with environmental changes; melatonin plays a vital role in regulating daily and seasonal variations. Due to rhythmic activity of the timezyme aralkylamine N-acetyltransferase (AANAT, the blood level of melatonin increases at night and decreases during daytime. Whereas other vertebrates have a single form of AANAT, bony fishes possess various isoforms of aanat genes, though the reasons are still unclear. Here, we have taken advantage of multiple unpublished teleost aanat sequences to explore and expand our understanding of the molecular evolution of aanat in fish. Our results confirm that two rounds of whole-genome duplication (WGD led to the existence of three fish isoforms of aanat, i.e., aanat1a, aanat1b, and aanat2; in addition, gene loss led to the absence of some forms from certain special fish species. Furthermore, we suggest the different roles of two aanat1s in amphibious mudskippers, and speculate that the loss of aanat1a, may be related to terrestrial vision change. Several important sites of AANAT proteins and regulatory elements of aanat genes were analyzed for structural comparison and functional forecasting, respectively, which provides insights into the molecular evolution of the differences between AANAT1 and AANAT2.

  6. Observations and modeling of the transiting exoplanets XO-2b, HAT-P-18b, and WASP-80b

    Directory of Open Access Journals (Sweden)

    Kjurkchieva Diana P.

    2017-01-01

    Full Text Available We present photometric observations and transit solutions of the exoplanets XO-2b, HAT-P-18b and WASP 80b. Our solution of the XO-2b transit gave system parameters whose values are close to those of the previous studies. The solutions of the new transits of HAT-P-18b and WASP 80b differ from the previous ones by bigger stellar and planet radii. We obtained new values of the target initial epochs corresponding to slightly different periods. Our investigation reaffirmed that small telescopes can be used successfully for the study of exoplanets orbiting stars brighter than 13 mag.

  7. Final audit report of remedial action construction at the UMTRA Project Mexican Hat, Utah -- Monument Valley, Arizona, sites

    International Nuclear Information System (INIS)

    1995-10-01

    The final audit report for remedial action at the Mexican Hat, Utah, Monument Valley, Arizona, Uranium Mill Tailings Remedial Action (UMTRA) Project sites consists of a summary of the radiological surveillances/audits, quality assurance (QA) in-process surveillances, and QA remedial action close-out inspections performed by the US Department of Energy (DOE) and the Technical Assistance Contractor (TAC); on-site construction reviews (OSCR) performed by the US Nuclear Regulatory Commission (NRC); and a surveillance performed by the Navajo Nation. This report refers to remedial action activities performed at the Mexican Hat, Utah--Monument Valley, Arizona, Uranium Mill Tailings Remedial Action (UMTRA) Project sites

  8. Three Point Bending of Top-Hat Stiffened Chopped Short Fibre Ramie/HDPE Thermoplastic Composite Beam

    Science.gov (United States)

    Hadi, Bambang K.; Nuril, Yogie S.

    2018-04-01

    The use of natural fibre and thermoplastic matrices in composite materials increased significantly during the last decade especially in the automotive industries. Ramie is one of these potential natural fibres. In this paper, a three point bending of top-hat beam made of ramie/HDPE (High-Density-Polyethylene) composites was performed. Top-hat stiffened structures were common structures found in the aerospace industries. Nevertheless, these structures are beginning to be applied in automotive structures in the forms of chassis and bumpers. The ramie/HDPE composite was manufactured using hot-press technique. The temperature was set to be 135°C and the pressure was 6 bars. Chopped short ramie fibre was used, due to good drape ability characteristics. The experiments showed that the beams produced a large non-linearity. Linear Finite Element Analysis was carried out to be compared with the experimental data. The differences are reasonable.

  9. Analyzing the public discourse on works of fiction - Detection and visualization of emotion in online coverage about HBO's Game of Thrones.

    Science.gov (United States)

    Scharl, Arno; Hubmann-Haidvogel, Alexander; Jones, Alistair; Fischl, Daniel; Kamolov, Ruslan; Weichselbraun, Albert; Rafelsberger, Walter

    2016-01-01

    This paper presents a Web intelligence portal that captures and aggregates news and social media coverage about "Game of Thrones", an American drama television series created for the HBO television network based on George R.R. Martin's series of fantasy novels. The system collects content from the Web sites of Anglo-American news media as well as from four social media platforms: Twitter, Facebook, Google+ and YouTube. An interactive dashboard with trend charts and synchronized visual analytics components not only shows how often Game of Thrones events and characters are being mentioned by journalists and viewers, but also provides a real-time account of concepts that are being associated with the unfolding storyline and each new episode. Positive or negative sentiment is computed automatically, which sheds light on the perception of actors and new plot elements.

  10. MRG15 activates the cdc2 promoter via histone acetylation in human cells

    International Nuclear Information System (INIS)

    Pena, AndreAna N.; Tominaga, Kaoru; Pereira-Smith, Olivia M.

    2011-01-01

    Chromatin remodeling is required for transcriptional activation and repression. MRG15 (MORF4L1), a chromatin modulator, is a highly conserved protein and is present in complexes containing histone acetyltransferases (HATs) as well as histone deacetylases (HDACs). Loss of expression of MRG15 in mice and Drosophila results in embryonic lethality and fibroblast and neural stem/progenitor cells cultured from Mrg15 null mouse embryos exhibit marked proliferative defects when compared with wild type cells. To determine the role of MRG15 in cell cycle progression we performed chromatin immunoprecipitation with an antibody to MRG15 on normal human fibroblasts as they entered the cell cycle from a quiescent state, and analyzed various cell cycle gene promoters. The results demonstrated a 3-fold increase in MRG15 occupancy at the cdc2 promoter during S phase of the cell cycle and a concomitant increase in acetylated histone H4. H4 lysine 12 was acetylated at 24 h post-serum stimulation while there was no change in acetylation of lysine 16. HDAC1 and 2 were decreased at this promoter during cell cycle progression. Over-expression of MRG15 in HeLa cells activated a cdc2 promoter-reporter construct in a dose-dependent manner, whereas knockdown of MRG15 resulted in decreased promoter activity. In order to implicate HAT activity, we treated cells with the HAT inhibitor anacardic acid and determined that HAT inhibition results in loss of expression of cdc2 mRNA. Further, chromatin immunoprecipitation with Tip60 localizes the protein to the same 110 bp stretch of the cdc2 promoter pulled down by MRG15. Additionally, we determined that cotransfection of MRG15 with the known associated HAT Tip60 had a cooperative effect in activating the cdc2 promoter. These results suggest that MRG15 is acting in a HAT complex involving Tip60 to modify chromatin via acetylation of histone H4 at the cdc2 promoter to activate transcription.

  11. MRG15 activates the cdc2 promoter via histone acetylation in human cells

    Energy Technology Data Exchange (ETDEWEB)

    Pena, AndreAna N., E-mail: andreana.pena@gmail.com [Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX (United States); Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX (United States); Tominaga, Kaoru; Pereira-Smith, Olivia M. [Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX (United States); Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX (United States)

    2011-07-01

    Chromatin remodeling is required for transcriptional activation and repression. MRG15 (MORF4L1), a chromatin modulator, is a highly conserved protein and is present in complexes containing histone acetyltransferases (HATs) as well as histone deacetylases (HDACs). Loss of expression of MRG15 in mice and Drosophila results in embryonic lethality and fibroblast and neural stem/progenitor cells cultured from Mrg15 null mouse embryos exhibit marked proliferative defects when compared with wild type cells. To determine the role of MRG15 in cell cycle progression we performed chromatin immunoprecipitation with an antibody to MRG15 on normal human fibroblasts as they entered the cell cycle from a quiescent state, and analyzed various cell cycle gene promoters. The results demonstrated a 3-fold increase in MRG15 occupancy at the cdc2 promoter during S phase of the cell cycle and a concomitant increase in acetylated histone H4. H4 lysine 12 was acetylated at 24 h post-serum stimulation while there was no change in acetylation of lysine 16. HDAC1 and 2 were decreased at this promoter during cell cycle progression. Over-expression of MRG15 in HeLa cells activated a cdc2 promoter-reporter construct in a dose-dependent manner, whereas knockdown of MRG15 resulted in decreased promoter activity. In order to implicate HAT activity, we treated cells with the HAT inhibitor anacardic acid and determined that HAT inhibition results in loss of expression of cdc2 mRNA. Further, chromatin immunoprecipitation with Tip60 localizes the protein to the same 110 bp stretch of the cdc2 promoter pulled down by MRG15. Additionally, we determined that cotransfection of MRG15 with the known associated HAT Tip60 had a cooperative effect in activating the cdc2 promoter. These results suggest that MRG15 is acting in a HAT complex involving Tip60 to modify chromatin via acetylation of histone H4 at the cdc2 promoter to activate transcription.

  12. Transiting Exoplanet Monitoring Project (TEMP). II. Refined System Parameters and Transit Timing Analysis of HAT-P-33b

    Science.gov (United States)

    Wang, Yong-Hao; Wang, Songhu; Liu, Hui-Gen; Hinse, Tobias C.; Laughlin, Gregory; Wu, Dong-Hong; Zhang, Xiaojia; Zhou, Xu; Wu, Zhenyu; Zhou, Ji-Lin; Wittenmyer, R. A.; Eastman, Jason; Zhang, Hui; Hori, Yasunori; Narita, Norio; Chen, Yuanyuan; Ma, Jun; Peng, Xiyan; Zhang, Tian-Meng; Zou, Hu; Nie, Jun-Dan; Zhou, Zhi-Min

    2017-08-01

    We present 10 R-band photometric observations of eight different transits of the hot Jupiter HAT-P-33b, which has been targeted by our Transiting Exoplanet Monitoring Project. The data were obtained by two telescopes at the Xinglong Station of National Astronomical Observatories of China (NAOC) from 2013 December through 2016 January, and exhibit photometric scatter of 1.6{--}3.0 {mmag}. After jointly analyzing the previously published photometric data, radial-velocity (RV) measurements, and our new light curves, we revisit the system parameters and orbital ephemeris for the HAT-P-33b system. Our results are consistent with the published values except for the planet to star radius ratio ({R}{{P}}/{R}* ), the ingress/egress duration (τ) and the total duration (T 14), which together indicate a slightly shallower and shorter transit shape. Our results are based on more complete light curves, whereas the previously published work had only one complete transit light curve. No significant anomalies in Transit Timing Variations (TTVs) are found, and we place upper mass limits on potential perturbers, largely supplanting the loose constraints provided by the extant RV data. The TTV limits are stronger near mean-motion resonances, especially for the low-order commensurabilities. We can exclude the existence of a perturber with mass larger than 0.6, 0.3, 0.5, 0.5, and 0.3 {M}\\oplus near the 1:3, 1:2, 2:3, 3:2, and 2:1 resonances, respectively.

  13. Complete genome sequence analysis of novel human bocavirus reveals genetic recombination between human bocavirus 2 and human bocavirus 4.

    Science.gov (United States)

    Khamrin, Pattara; Okitsu, Shoko; Ushijima, Hiroshi; Maneekarn, Niwat

    2013-07-01

    Epidemiological surveillance of human bocavirus (HBoV) was conducted on fecal specimens collected from hospitalized children with diarrhea in Chiang Mai, Thailand in 2011. By partial sequence analysis of VP1 gene, an unusual strain of HBoV (CMH-S011-11), was initially identified as HBoV4. The complete genome sequence of CMH-S011-11 was performed and analyzed further to clarify whether it was a recombinant strain or a new HBoV variant. Analysis of complete genome sequence revealed that the coding sequence starting from NS1, NP1 to VP1/VP2 was 4795 nucleotides long. Interestingly, the nucleotide sequence of NS1 gene of CMH-S011-11 was most closely related to the HBoV2 reference strains detected in Pakistan, which contradicted to the initial genotyping result of the partial VP1 region in the previous study. In addition, comparison of NP1 nucleotide sequence of CMH-S011-11 with those of other HBoV1-4 reference strains also revealed a high level of sequence identity with HBoV2. On the other hand, nucleotide sequence of VP1/VP2 gene of CMH-S011-11 was most closely related to those of HBoV4 reference strains detected in Nigeria. The overall full-length sequence analysis revealed that this CMH-S011-11 was grouped within HBoV4 species, but located in a separate branch from other HBoV4 prototype strains. Recombination analysis revealed that CMH-S011-11 was the result of recombination between HBoV2 and HBoV4 strains with the break point located near the start codon of VP2. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Hyperbaric Oxygen therapy effects on bone regeneration in Type 1 diabetes mellitus in rats.

    Science.gov (United States)

    Dias, Pâmella Coelho; Limirio, Pedro Henrique Justino Oliveira; Linhares, Camila Rodrigues Borges; Bergamini, Mariana Lobo; Rocha, Flaviana Soares; Morais, Richarlisson Borges de; Balbi, Ana Paula Coelho; Hiraki, Karen Renata Nakamura; Dechichi, Paula

    2018-01-29

    The aim of this study was evaluate the effect of HBO on diabetic rats. Twenty rats were distributed into four groups (n = 5): Control (C); Control + HBO (CH); Diabetes (D) and Diabetes + HBO (DH). Diabetes was induced by streptozotocin, and bone defects were created in both femurs in all animals. HBO therapy began immediately after surgery and was performed daily in the CH and DH groups. After 7 days, the animals were euthanized. The femurs were removed, demineralized, embedded in paraffin, and histologic images were analyzed. Qualitative histologic analyses showed more advanced stage bone regeneration in control groups (C and CH) compared with diabetic groups (D and DH). Histomorphometric analysis showed significantly increased bone neoformation in CH compared with the other groups (p  0.05). The mast cell population increased in CH compared with the other groups (C, D, and DH) (p < 0.05). The mast cell population did not differ between D and DH Groups. This study showed that HBO therapy improved early bone regeneration in diabetic rats and increased the mast cell population only in non-diabetic animals. HBO was shown to be important treatment for minimizing deleterious effects of diabetes on bone regeneration.

  15. Histone acetyltransferase PCAF is required for Hedgehog-Gli-dependent transcription and cancer cell proliferation

    DEFF Research Database (Denmark)

    Malatesta, Martina; Steinhauer, Cornelia; Mohammad, Faizaan

    2013-01-01

    The Hedgehog (Hh) signaling pathway plays an important role in embryonic patterning and development of many tissues and organs as well as in maintaining and repairing mature tissues in adults. Uncontrolled activation of the Hh-Gli pathway has been implicated in developmental abnormalities as well...... that the histone acetyltransferase PCAF/KAT2B is an important factor of the Hh pathway. Specifically, we show that PCAF depletion impairs Hh activity and reduces expression of Hh target genes. Consequently, PCAF downregulation in medulloblastoma and glioblastoma cells leads to decreased proliferation and increased...... apoptosis. In addition, we found that PCAF interacts with GLI1, the downstream effector in the Hh-Gli pathway, and that PCAF or GLI1 loss reduces the levels of H3K9 acetylation on Hh target gene promoters. Finally, we observed that PCAF silencing reduces the tumor-forming potential of neural stem cells...

  16. UMTRA Project Site Observational Work Plan, Mexican Hat, Utah

    International Nuclear Information System (INIS)

    1994-09-01

    Surface cleanup activities at the Mexican Hat UMTRA processing site are nearing completion. Ground Water contamination at the Mexican Hat site is a result of uranium milling operations. The extent of residual process water has been identified, and it is limited to the uppermost aquifer in the vicinity of the site. Deeper aquifers are not affected because of an upward hydraulic gradient and the presence of a confining unit (the deeper aquifers are protected by hydrogeologic isolation). The uppermost unit is returning to its pre-milling, mainly unsaturated state. The unit that contains the contaminated water is not a ground water resource because it qualifies as Class III (limited use) based on limited yield. Ground water in the uppermost unit is currently not used and is not anticipated to be used as a ground water resource. The nearby San Juan River and a converted oil exploration well provide all of the water needs for the area. There are no current threats to human health or livestock; and, because the zone of contamination does not represent a ground water resource, none are anticipated in the future. There are, however, seeps where contaminated water is exposed at land surface. The seeps create potential exposure pathways for plants and wildlife. It is not known at this time if there is a risk to the environment. Additional investigations are needed and are described in this document to confirm the presence or absence of potential environmental risks. Additional hydrogeologic investigations are not required. The proposed ground water compliance strategy for the site is no remediation, because the ground water in the uppermost aquifer (which is also the zone of contamination) qualifies for supplemental standards based on Class III, limited yield, and because there are no threats to human health. Domestic and agricultural water is pumped from a deeper aquifer that is isolated from the contaminated zone

  17. Assessment of seeps in the vicinity of the Mexican Hat tailings disposal cell

    International Nuclear Information System (INIS)

    1990-10-01

    The Phase II remedial action at the Mexican Hat site began in September 1988, and involved the excavation, transportation, and placement of contaminated materials onto the lower tailings pile. These materials were from the upper tailings pile, portions of the lower tailings pile, off-pile contaminated areas, and demolition material stockpiled at the former-mill site. By December 1989, all of the contaminated soils on the upper tailings pile area and most of the off-pile windblown and waterborne contamination had been removed and placed on the lower pile. Since that time, several seeps have been observed near the site. These seeps and some previously identified seeps may be related to remedial action construction activities or the past disposal of mill tailings at the Mexican Hat site. The objectives of this report are to: summarize the geology and hydrostratigraphy of the site; discuss field investigation of the locations, chronology, and flow rates of the seeps; discuss background groundwater quality, tailings pore fluid characterization, and water quality of the seeps; identify possible sources of the seeps; interpret the data; make recommendations for continued site characterization and assessment

  18. RG domain wall for the general (su)-hat (2) coset models

    Energy Technology Data Exchange (ETDEWEB)

    Stanishkov, Marian [Institute for Nuclear Research and Nuclear Energy,Bulgarian Academy of Sciences, 1784 Sofia (Bulgaria)

    2016-08-16

    We consider a RG flow in a general (su)-hat (2) coset model induced by the least relevant field. This is done using two different approaches. We first compute the mixing coefficients of certain fields in the UV and IR theories using a conformal perturbation theory. The necessary structure constants are computed. The same coefficients can be calculated using the RG domain wall construction of Gaiotto. We compute the corresponding one-point functions and show that the two approaches give the same result in the leading order.

  19. Resveratrol Promotes Nerve Regeneration via Activation of p300 Acetyltransferase-Mediated VEGF Signaling in a Rat Model of Sciatic Nerve Crush Injury.

    Science.gov (United States)

    Ding, Zhuofeng; Cao, Jiawei; Shen, Yu; Zou, Yu; Yang, Xin; Zhou, Wen; Guo, Qulian; Huang, Changsheng

    2018-01-01

    Peripheral nerve injuries are generally associated with incomplete restoration of motor function. The slow rate of nerve regeneration after injury may account for this. Although many benefits of resveratrol have been shown in the nervous system, it is not clear whether resveratrol could promote fast nerve regeneration and motor repair after peripheral nerve injury. This study showed that the motor deficits caused by sciatic nerve crush injury were alleviated by daily systematic resveratrol treatment within 10 days. Resveratrol increased the number of axons in the distal part of the injured nerve, indicating enhanced nerve regeneration. In the affected ventral spinal cord, resveratrol enhanced the expression of several vascular endothelial growth factor family proteins (VEGFs) and increased the phosphorylation of p300 through Akt signaling, indicating activation of p300 acetyltransferase. Inactivation of p300 acetyltransferase reversed the resveratrol-induced expression of VEGFs and motor repair in rats that had undergone sciatic nerve crush injury. The above results indicated that daily systematic resveratrol treatment promoted nerve regeneration and led to rapid motor repair. Resveratrol activated p300 acetyltransferase-mediated VEGF signaling in the affected ventral spinal cord, which may have thus contributed to the acceleration of nerve regeneration and motor repair.

  20. Regulation of Histone Acetyltransferase TIP60 Function by Histone Deacetylase 3

    Science.gov (United States)

    Yi, Jingjie; Huang, Xiangyang; Yang, Yuxia; Zhu, Wei-Guo; Gu, Wei; Luo, Jianyuan

    2014-01-01

    The key member of the MOZ (monocyticleukaemia zinc finger protein), Ybf2/Sas3, Sas2, and TIP60 acetyltransferases family, Tat-interactive protein, 60 kD (TIP60), tightly modulates a wide array of cellular processes, including chromatin remodeling, gene transcription, apoptosis, DNA repair, and cell cycle arrest. The function of TIP60 can be regulated by SIRT1 through deacetylation. Here we found that TIP60 can also be functionally regulated by HDAC3. We identified six lysine residues as its autoacetylation sites. Mutagenesis of these lysines to arginines completely abolishes the autoacetylation of TIP60. Overexpression of HDAC3 increases TIP60 ubiquitination levels. However, unlike SIRT1, HDAC3 increased the half-life of TIP60. Further study found that HDAC3 colocalized with TIP60 both in the nucleus and the cytoplasm, which could be the reason why HDAC3 can stabilize TIP60. The deacetylation of TIP60 by both SIRT1 and HDAC3 reduces apoptosis induced by DNA damage. Knockdown of HDAC3 in cells increased TIP60 acetylation levels and increased apoptosis after DNA damage. Together, our findings provide a better understanding of TIP60 regulation mechanisms, which is a significant basis for further studies of its cellular functions. PMID:25301942

  1. 3D structure prediction of histone acetyltransferase (HAC proteins of the p300/CBP family and their interactome in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Amar Cemanovic

    2014-09-01

    Full Text Available Histone acetylation is an important posttranslational modification correlated with gene activation. In Arabidopsis thaliana the histone acetyltransferase (HAC proteins of the CBP family are homologous to animal p300/CREB (cAMP-responsive element-binding proteins, which are important histone acetyltransferases participating in many physiological processes, including proliferation, differentiation, and apoptosis. In this study the 3-D structure of all HAC protein subunits in Arabidopsis thaliana: HAC1, HAC2, HAC4, HAC5 and HAC12 is predicted by homology modeling and confirmed by Ramachandran plot analysis. The amino acid sequences HAC family members are highly similar to the sequences of the homologous human p300/CREB protein. Conservation of p300/CBP domains among the HAC proteins was examined further by sequence alignment and pattern search. The domains of p300/CBP required for the HAC function, such as PHD, TAZ and ZZ domains, are conserved in all HAC proteins. Interactome analysis revealed that HAC1, HAC5 and HAC12 proteins interact with S-adenosylmethionine-dependent methyltransferase domaincontaining protein that shows methyltransferase activity, suggesting an additional function of the HAC proteins. Additionally, HAC5 has a strong interaction value for the putative c-myb-like transcription factor MYB3R-4, which suggests that it also may have a function in regulation of DNA replication.

  2. Purification, crystallization and preliminary X-ray analysis of the aminoglycoside-6′-acetyltransferase AAC(6′)-Im

    International Nuclear Information System (INIS)

    Toth, Marta; Vakulenko, Sergei B.; Smith, Clyde A.

    2012-01-01

    AAC(6′)-Im is an N-acetyltransferase enzyme responsible for aminoglycoside resistance in E. faecium and E. coli isolates. Crystals of the kanamycin complex of this enzyme have been prepared and preliminary X-ray diffraction experiments have been undertaken. Bacterial resistance to the aminoglycoside antibiotics is primarily the result of enzymatic deactivation of the drugs. The aminoglycoside N-acetyltransferases (AACs) are a large family of bacterial enzymes that are responsible for coenzyme-A-facilitated acetylation of aminoglycosides. The gene encoding one of these enzymes, AAC(6′)-Im, has been cloned and the protein (comprising 178 amino-acid residues) was expressed in Escherichia coli, purified and crystallized as the kanamycin complex. Synchrotron diffraction data to approximately 2.0 Å resolution were collected from a crystal of this complex on beamline BL12-2 at SSRL (Stanford, California, USA). The crystals belonged to the hexagonal space group P6 5 , with approximate unit-cell parameters a = 107.75, c = 37.33 Å, and contained one molecule in the asymmetric unit. Structure determination is under way using molecular replacement

  3. Warm Spitzer and Palomar near-IR secondary eclipse photometry of two hot Jupiters: WASP-48b and HAT-P-23b

    Energy Technology Data Exchange (ETDEWEB)

    O' Rourke, Joseph G.; Knutson, Heather A.; Désert, Jean-Michel [Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125 (United States); Zhao, Ming [Department of Astronomy and Astrophysics, 525 Davey Laboratory, The Pennsylvania State University, University Park, PA 16802 (United States); Fortney, Jonathan J. [Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States); Burrows, Adam [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 05844 (United States); Agol, Eric [Department of Astronomy, University of Washington, Box 351580, Seattle, WA 98195 (United States); Deming, Drake [Department of Astronomy, University of Maryland, College Park, MD 20742 (United States); Howard, Andrew W. [Institute for Astronomy, University of Hawaii, 2680 Woodlawn Drive, Honolulu, HI 96822 (United States); Lewis, Nikole K. [Department of Earth, Atmospheric, and Planetary Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Showman, Adam P. [Lunar and Planetary Laboratory, University of Arizona, Tucson, AZ 85721 (United States); Todorov, Kamen O. [Institute for Astronomy, ETH Zürich, Wolfgang-Pauli-Strasse 27, 8093 Zürich (Switzerland)

    2014-02-01

    We report secondary eclipse photometry of two hot Jupiters, WASP-48b and HAT-P-23b, at 3.6 and 4.5 μm taken with the InfraRed Array Camera aboard the Spitzer Space Telescope during the warm Spitzer mission and in the H and K{sub S} bands with the Wide Field IR Camera at the Palomar 200 inch Hale Telescope. WASP-48b and HAT-P-23b are Jupiter-mass and twice Jupiter-mass objects orbiting an old, slightly evolved F star and an early G dwarf star, respectively. In the H, K{sub S} , 3.6 μm, and 4.5 μm bands, respectively, we measure secondary eclipse depths of 0.047% ± 0.016%, 0.109% ± 0.027%, 0.176% ± 0.013%, and 0.214% ± 0.020% for WASP-48b. In the K{sub S} , 3.6 μm, and 4.5 μm bands, respectively, we measure secondary eclipse depths of 0.234% ± 0.046%, 0.248% ± 0.019%, and 0.309% ± 0.026% for HAT-P-23b. For WASP-48b and HAT-P-23b, respectively, we measure delays of 2.6 ± 3.9 minutes and 4.0 ± 2.4 minutes relative to the predicted times of secondary eclipse for circular orbits, placing 2σ upper limits on |ecos ω| of 0.0053 and 0.0080, both of which are consistent with circular orbits. The dayside emission spectra of these planets are well-described by blackbodies with effective temperatures of 2158 ± 100 K (WASP-48b) and 2154 ± 90 K (HAT-P-23b), corresponding to moderate recirculation in the zero albedo case. Our measured eclipse depths are also consistent with one-dimensional radiative transfer models featuring varying degrees of recirculation and weak thermal inversions or no inversions at all. We discuss how the absence of strong temperature inversions on these planets may be related to the activity levels and metallicities of their host stars.

  4. Design and evaluation of a foam-filled hat-stiffened panel concept for aircraft primary structural applications

    Science.gov (United States)

    Ambur, Damodar R.

    1995-01-01

    A structurally efficient hat-stiffened panel concept that utilizes a structural foam as stiffener core has been designed for aircraft primary structural applications. This stiffener concept utilizes a manufacturing process that can be adapted readily to grid-stiffened structural configurations which possess inherent damage tolerance characteristics due to their multiplicity of load paths. The foam-filled hat-stiffener concept in a prismatically stiffened panel configuration is more efficient than most other stiffened panel configurations in a load range that is typical for both fuselage and wing structures. The prismatically stiffened panel concept investigated here has been designed using AS4/3502 preimpregnated tape and Rohacell foam core and evaluated for its buckling and postbuckling behavior with and without low-speed impact damage. The results from single-stiffener and multi-stiffener specimens suggest that this structural concept responds to loading as anticipated and has good damage tolerance characteristics.

  5. KEPLER'S OPTICAL SECONDARY ECLIPSE OF HAT-P-7b AND PROBABLE DETECTION OF PLANET-INDUCED STELLAR GRAVITY DARKENING

    Energy Technology Data Exchange (ETDEWEB)

    Morris, Brett M.; Deming, Drake [Department of Astronomy, University of Maryland, College Park, MD 20742 (United States); Mandell, Avi M. [Goddard Center for Astrobiology, NASA' s Goddard Space Flight Center, Greenbelt, MD 20771 (United States)

    2013-02-20

    We present observations spanning 355 orbital phases of HAT-P-7 observed by Kepler from 2009 May to 2011 March (Q1-9). We find a shallower secondary eclipse depth than initially announced, consistent with a low optical albedo and detection of nearly exclusively thermal emission, without a reflected light component. We find an approximately 10 ppm perturbation to the average transit light curve near phase -0.02 that we attribute to a temperature decrease on the surface of the star, phased to the orbit of the planet. This cooler spot is consistent with planet-induced gravity darkening, slightly lagging the sub-planet position due to the finite response time of the stellar atmosphere. The brightness temperature of HAT-P-7b in the Kepler bandpass is T{sub B} = 2733 {+-} 21 K and the amplitude of the deviation in stellar surface temperature due to gravity darkening is approximately -0.18 K. The detection of the spot is not statistically unequivocal due its small amplitude, though additional Kepler observations should be able to verify the astrophysical nature of the anomaly.

  6. Analysis of Myc-induced histone modifications on target chromatin.

    Directory of Open Access Journals (Sweden)

    Francesca Martinato

    Full Text Available The c-myc proto-oncogene is induced by mitogens and is a central regulator of cell growth and differentiation. The c-myc product, Myc, is a transcription factor that binds a multitude of genomic sites, estimated to be over 10-15% of all promoter regions. Target promoters generally pre-exist in an active or poised chromatin state that is further modified by Myc, contributing to fine transcriptional regulation (activation or repression of the afferent gene. Among other mechanisms, Myc recruits histone acetyl-transferases to target chromatin and locally promotes hyper-acetylation of multiple lysines on histones H3 and H4, although the identity and combination of the modified lysines is unknown. Whether Myc dynamically regulates other histone modifications (or marks at its binding sites also remains to be addressed. Here, we used quantitative chromatin immunoprecipitation (qChIP to profile a total of 24 lysine-acetylation and -methylation marks modulated by Myc at target promoters in a human B-cell line with a regulatable c-myc transgene. Myc binding promoted acetylation of multiple lysines, primarily of H3K9, H3K14, H3K18, H4K5 and H4K12, but significantly also of H4K8, H4K91 and H2AK5. Dimethylation of H3K79 was also selectively induced at target promoters. A majority of target promoters showed co-induction of multiple marks - in various combinations - correlating with recruitment of the two HATs tested (Tip60 and HBO1, incorporation of the histone variant H2A.Z and transcriptional activation. Based on this and previous findings, we surmise that Myc recruits the Tip60/p400 complex to achieve a coordinated histone acetylation/exchange reaction at activated promoters. Our data are also consistent with the additive and redundant role of multiple acetylation events in transcriptional activation.

  7. Bifurcated Degradative Pathway of 3-Sulfolactate in Roseovarius nubinhibens ISM via Sulfoacetaldehyde Acetyltransferase and (S)-Cysteate Sulfolyase ▿ †

    Science.gov (United States)

    Denger, Karin; Mayer, Jutta; Buhmann, Matthias; Weinitschke, Sonja; Smits, Theo H. M.; Cook, Alasdair M.

    2009-01-01

    Data from the genome sequence of the aerobic, marine bacterium Roseovarius nubinhibens ISM were interpreted such that 3-sulfolactate would be degraded as a sole source of carbon and energy for growth via a novel bifurcated pathway including two known desulfonative enzymes, sulfoacetaldehyde acetyltransferase (EC 2.3.3.15) (Xsc) and cysteate sulfo-lyase (EC 4.4.1.25) (CuyA). Strain ISM utilized sulfolactate quantitatively with stoichiometric excretion of the sulfonate sulfur as sulfate. A combination of enzyme assays, analytical chemistry, enzyme purification, peptide mass fingerprinting, and reverse transcription-PCR data supported the presence of an inducible, tripartite sulfolactate uptake system (SlcHFG), and a membrane-bound sulfolactate dehydrogenase (SlcD) which generated 3-sulfopyruvate, the point of bifurcation. 3-Sulfopyruvate was in part decarboxylated by 3-sulfopyruvate decarboxylase (EC 4.1.1.79) (ComDE), which was purified. The sulfoacetaldehyde that was formed was desulfonated by Xsc, which was identified, and the acetyl phosphate was converted to acetyl-coenzyme A by phosphate acetyltransferase (Pta). The other portion of the 3-sulfopyruvate was transaminated to (S)-cysteate, which was desulfonated by CuyA, which was identified. The sulfite that was formed was presumably exported by CuyZ (TC 9.B.7.1.1 in the transport classification system), and a periplasmic sulfite dehydrogenase is presumed. Bioinformatic analyses indicated that transporter SlcHFG is rare but that SlcD is involved in three different combinations of pathways, the bifurcated pathway shown here, via CuyA alone, and via Xsc alone. This novel pathway involves ComDE in biodegradation, whereas it was discovered in the biosynthesis of coenzyme M. The different pathways of desulfonation of sulfolactate presumably represent final steps in the biodegradation of sulfoquinovose (and exudates derived from it) in marine and aquatic environments. PMID:19581363

  8. Magic hat economics: counter-cultural ideals and practices of the Nordic Ting community

    Directory of Open Access Journals (Sweden)

    Janne Juhana Rantala

    2009-01-01

    Full Text Available The author's anthropological study concerns one of today’s communities with no shared belief system, but with a clear spiritualist orientation. The Nordic Ting Community does not have any defined or committing roles, specialized distribution of tasks, entrance fee to their two annual gatherings, membership or any formal hierarchy. This exiguity of structural differentiation could well be understood to represent ‘subjective spirituality’. This thesis refers to the decline of institutional forms of religion with, instead, an increase in subjective experience in spirituality. This presentation shows that at least in the author's field of study, there hardly exists any increase in emphasis on individualism in spirituality. Instead the material indicates a relatively long continuum of a self-organized type of communality which could be understood as neither individualistic nor collectivistic. The type of agency observed in the social action of the studied network-like field is intersubjective. This article focuses on the use of the magic hat and the combination of ideals and practices characteristic to the Ting Community, which the author calls the magic hat economics. It is argued that by looking at these kinds of intermediating objects, the problem of individualization can be seen much more clearly

  9. TCUP: A novel hAT transposon active in maize tissue culture

    Directory of Open Access Journals (Sweden)

    Alan eSmith

    2012-01-01

    Full Text Available Transposable elements are capable of inducing heritable de novo genetic variation. The sequences capable of reactivation, and environmental factors that induce mobilization, remain poorly defined even in well-studied genomes such as maize. We treated maize tissue culture with the demethylating agent 5-aza-2-deoxcytidine and examined long-term tissue culture lines to discover silenced transposable elements that have the potential to induce heritable genetic variation. Through these screens we have identified a novel low copy number hAT transposon, Tissue Culture Up-Regulated (TCUP, which is transcribed at high levels in long-term maize Black Mexican Sweet (BMS tissue culture and up-regulated in response to treatment with 5-aza-2-deoxycytidine. Analysis of the TIGR Maize Gene Index revealed that this element is the most frequently represented EST from the BMS cell culture library and is not represented in other tissue libraries, which is the basis for its name. A full-length sequence was assembled in inbred B73 that contains the putative functional motifs required for autonomous movement of a hAT transposon. Transposon display detected movement of TCUP in two long-term tissue cultured cell lines of the genotype Hi-II AxB and BMS. This research implicates TCUP as a transposon that is capable of reactivation and which may also be particularly sensitive to the stress of the tissue culture environment. Our findings are consistent with the hypothesis that epigenetic alterations potentiate genomic responses to stress during clonal propagation of plants.

  10. Substrate-Induced Allosteric Change in the Quaternary Structure of the Spermidine N-Acetyltransferase SpeG

    OpenAIRE

    Filippova, Ekaterina V.; Weigand, Steven; Osipiuk, Jerzy; Kiryukhina, Olga; Joachimiak, Andrzej; Anderson, Wayne F.

    2015-01-01

    The spermidine N-acetyltransferase SpeG is a dodecameric enzyme that catalyzes the transfer of an acetyl group from acetyl-coenzyme A to polyamines such as spermidine and spermine. SpeG has an allosteric polyamine-binding site and acetylating polyamines regulates their intracellular concentrations. The structures of SpeG from Vibrio cholerae in complexes with polyamines and cofactor have been characterized earlier. Here, we present the dodecameric structure of SpeG from V. cholerae in a ligan...

  11. Crystal structure of inhibitor of growth 4 (ING4) dimerization domain reveals functional organization of ING family of chromatin-binding proteins.

    Science.gov (United States)

    Culurgioni, Simone; Muñoz, Inés G; Moreno, Alberto; Palacios, Alicia; Villate, Maider; Palmero, Ignacio; Montoya, Guillermo; Blanco, Francisco J

    2012-03-30

    The protein ING4 binds to histone H3 trimethylated at Lys-4 (H3K4me3) through its C-terminal plant homeodomain, thus recruiting the HBO1 histone acetyltransferase complex to target promoters. The structure of the plant homeodomain finger bound to an H3K4me3 peptide has been described, as well as the disorder and flexibility in the ING4 central region. We report the crystal structure of the ING4 N-terminal domain, which shows an antiparallel coiled-coil homodimer with each protomer folded into a helix-loop-helix structure. This arrangement suggests that ING4 can bind simultaneously two histone tails on the same or different nucleosomes. Dimerization has a direct impact on ING4 tumor suppressor activity because monomeric mutants lose the ability to induce apoptosis after genotoxic stress. Homology modeling based on the ING4 structure suggests that other ING dimers may also exist.

  12. Biochemical and Structural Analysis of an Eis Family Aminoglycoside Acetyltransferase from Bacillus anthracis

    Energy Technology Data Exchange (ETDEWEB)

    Green, Keith D.; Biswas, Tapan; Chang, Changsoo; Wu, Ruiying; Chen, Wenjing; Janes, Brian K.; Chalupska, Dominika; Gornicki, Piotr; Hanna, Philip C.; Tsodikov, Oleg V.; Joachimiak, Andrzej; Garneau-Tsodikova, Sylvie

    2015-05-26

    Proteins from the enhanced intracellular survival (Eis) family are versatile acetyltransferases that acetylate amines at multiple positions of several aminoglycosides (AGs). Their upregulation confers drug resistance. Homologues of Eis are present in diverse bacteria, including many pathogens. Eis from Mycobacterium tuberculosis (Eis_Mtb) has been well characterized. In this study, we explored the AG specificity and catalytic efficiency of the Eis family protein from Bacillus anthracis (Eis_Ban). Kinetic analysis of specificity and catalytic efficiency of acetylation of six AGs indicates that Eis_Ban displays significant differences from Eis_Mtb in both substrate binding and catalytic efficiency. The number of acetylated amines was also different for several AGs, indicating a distinct regiospecificity of Eis_Ban. Furthermore, most recently identified inhibitors of Eis_Mtb did not inhibit Eis_Ban, underscoring the differences between these two enzymes. To explain these differences, we determined an Eis_Ban crystal structure. The comparison of the crystal structures of Eis_Ban and Eis_Mtb demonstrates that critical residues lining their respective substrate binding pockets differ substantially, explaining their distinct specificities. Our results suggest that acetyltransferases of the Eis family evolved divergently to garner distinct specificities while conserving catalytic efficiency, possibly to counter distinct chemical challenges. The unique specificity features of these enzymes can be utilized as tools for developing AGs with novel modifications and help guide specific AG treatments to avoid Eis-mediated resistance.

  13. Choline acetyltransferase-containing neurons in the human parietal neocortex

    Directory of Open Access Journals (Sweden)

    V Benagiano

    2009-06-01

    Full Text Available A number of immunocytochemical studies have indicated the presence of cholinergic neurons in the cerebral cortex of various species of mammals. Whether such cholinergic neurons in the human cerebral cortex are exclusively of subcortical origin is still debated. In this immunocytochemical study, the existence of cortical cholinergic neurons was investigated on surgical samples of human parietal association neocortex using a highly specific monoclonal antibody against choline acetyltransferase (ChAT, the acetylcholine biosynthesising enzyme. ChAT immunoreactivity was detected in a subpopulation of neurons located in layers II and III. These were small or medium-sized pyramidal neurons which showed cytoplasmic immunoreactivity in the perikarya and processes, often in close association to blood microvessels. This study, providing demonstration of ChAT neurons in the human parietal neocortex, strongly supports the existence of intrinsic cholinergic innervation of the human neocortex. It is likely that these neurons contribute to the cholinergic innervation of the intracortical microvessels.

  14. Combination Treatments with Luteolin and Fisetin Enhance Anti-Inflammatory Effects in High Glucose-Treated THP-1 Cells Through Histone Acetyltransferase/Histone Deacetylase Regulation.

    Science.gov (United States)

    Kim, Arang; Yun, Jung-Mi

    2017-08-01

    Hyperglycemia leads to diabetes and its diabetic complications. In this study, we investigated the synergistic effects of luteolin and fisetin on proinflammatory cytokine secretion and its underlying epigenetic regulation in human monocytes exposed to hyperglycemic (HG) concentrations. Human monocytic cells (THP-1) were cultured under controlled (14.5 mM mannitol), normoglycemic (5.5 mM glucose), or HG (20 mM glucose) conditions in the absence or presence of the two phytochemicals for 48 h. Whereas HG conditions significantly induced histone acetylation, nuclear factor-kappa B (NF-κB) activation, interleukin 6, and tumor necrosis factor-α release from THP-1 cells; combination treatments with the two phytochemicals (500 nM fisetin, and l μM and 500 nM luteolin) suppressed NF-κB activity and inflammatory cytokine release. Fisetin, luteolin, and their combination treatments also significantly decreased the activity of histone acetyltransferase, a known NF-κB coactivator; inhibited reactive oxygen species production; and activated sirtuin (SIRT)1 and forkhead box O3a (FOXO3a) expressions (P < .05). Thus, combination treatments with the two phytochemicals inhibited HG condition-induced cytokine production in monocytes, through epigenetic changes involving NF-κB activation. We, therefore, suggest that combination treatments with luteolin and fisetin may be a potential candidate for the treatment and prevention of diabetes and its complications.

  15. HAT-P-65b and HAT-P-66b: Two Transiting Inflated Hot Jupiters and Observational Evidence for the Reinflation of Close-in Giant Planets

    Science.gov (United States)

    Hartman, J. D.; Bakos, G. Á.; Bhatti, W.; Penev, K.; Bieryla, A.; Latham, D. W.; Kovács, G.; Torres, G.; Csubry, Z.; de Val-Borro, M.; Buchhave, L.; Kovács, T.; Quinn, S.; Howard, A. W.; Isaacson, H.; Fulton, B. J.; Everett, M. E.; Esquerdo, G.; Béky, B.; Szklenar, T.; Falco, E.; Santerne, A.; Boisse, I.; Hébrard, G.; Burrows, A.; Lázár, J.; Papp, I.; Sári, P.

    2016-12-01

    We present the discovery of the transiting exoplanets HAT-P-65b and HAT-P-66b, with orbital periods of 2.6055 and 2.9721 days, masses of 0.527+/- 0.083 {M}{{J}} and 0.783+/- 0.057 {M}{{J}}, and inflated radii of 1.89+/- 0.13 {R}{{J}} and {1.59}-0.10+0.16 {R}{{J}}, respectively. They orbit moderately bright (V=13.145+/- 0.029 and V=12.993+/- 0.052) stars of mass 1.212+/- 0.050 {M}⊙ and {1.255}-0.054+0.107 {M}⊙ . The stars are at the main-sequence turnoff. While it is well known that the radii of close-in giant planets are correlated with their equilibrium temperatures, whether or not the radii of planets increase in time as their hosts evolve and become more luminous is an open question. Looking at the broader sample of well-characterized close-in transiting giant planets, we find that there is a statistically significant correlation between planetary radii and the fractional ages of their host stars, with a false-alarm probability of only 0.0041%. We find that the correlation between the radii of planets and the fractional ages of their hosts is fully explained by the known correlation between planetary radii and their present-day equilibrium temperatures; however, if the zero-age main-sequence equilibrium temperature is used in place of the present-day equilibrium temperature, then a correlation with age must also be included to explain the planetary radii. This suggests that, after contracting during the pre-main-sequence, close-in giant planets are reinflated over time due to the increasing level of irradiation received from their host stars. Prior theoretical work indicates that such a dynamic response to irradiation requires a significant fraction of the incident energy to be deposited deep within the planetary interiors. Based on observations obtained with the Hungarian-made Automated Telescope Network. Based on observations obtained at the W. M. Keck Observatory, which is operated by the University of California and the California Institute of Technology

  16. Density functional calculations of potential energy surface and charge transfer integrals in molecular triphenylene derivative HAT6

    NARCIS (Netherlands)

    Zbiri, M.; Johnson, M.R.; Kearley, G.J.; Mulder, F.M.

    2009-01-01

    We investigate the effect of structural fluctuations on charge transfer integrals, overlap integrals, and site energies in a system of two stacked molecular 2,3,6,7,10,11-hexakishexyloxytriphenylene (HAT6), which is a model system for conducting devices in organic photocell applications. A density

  17. Depression of nocturnal pineal serotonin N-acetyltransferase activity in castrate male rats

    International Nuclear Information System (INIS)

    Rudeen, P.K.; Reiter, R.J.; Texas Univ., San Antonio

    1980-01-01

    Pineal serotonin N-acetyltransferase (NAT) activity was examined in intact rats, castrated rats, and in rats that had been castrated and had received testosterone proprionate. Castration resulted in significantly depressing nocturnal levels of pineal NAT (p<0.05) when compared to enzyme activity in intact rats. Testosterone proprionate administration restored plasma LH levels to normal values in castrate rats but did not induce nocturnal pineal enzyme activity to levels seen in the pineal glands of intact rats. The data substantiate the existence of a feedback control of pineal biosynthetic activity by the hypophyseal-gonadal system, but the identity of the hormone(s) responsible for regulation of pineal NAT activity is not known. (author)

  18. Structural basis of hAT transposon end recognition by Hermes, an octameric DNA transposase from Musca domestica.

    Science.gov (United States)

    Hickman, Alison B; Ewis, Hosam E; Li, Xianghong; Knapp, Joshua A; Laver, Thomas; Doss, Anna-Louise; Tolun, Gökhan; Steven, Alasdair C; Grishaev, Alexander; Bax, Ad; Atkinson, Peter W; Craig, Nancy L; Dyda, Fred

    2014-07-17

    Hermes is a member of the hAT transposon superfamily that has active representatives, including McClintock's archetypal Ac mobile genetic element, in many eukaryotic species. The crystal structure of the Hermes transposase-DNA complex reveals that Hermes forms an octameric ring organized as a tetramer of dimers. Although isolated dimers are active in vitro for all the chemical steps of transposition, only octamers are active in vivo. The octamer can provide not only multiple specific DNA-binding domains to recognize repeated subterminal sequences within the transposon ends, which are important for activity, but also multiple nonspecific DNA binding surfaces for target capture. The unusual assembly explains the basis of bipartite DNA recognition at hAT transposon ends, provides a rationale for transposon end asymmetry, and suggests how the avidity provided by multiple sites of interaction could allow a transposase to locate its transposon ends amidst a sea of chromosomal DNA. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. The Multiscale Bowler-Hat Transform for Vessel Enhancement in 3D Biomedical Images

    OpenAIRE

    Sazak, Cigdem; Nelson, Carl J.; Obara, Boguslaw

    2018-01-01

    Enhancement and detection of 3D vessel-like structures has long been an open problem as most existing image processing methods fail in many aspects, including a lack of uniform enhancement between vessels of different radii and a lack of enhancement at the junctions. Here, we propose a method based on mathematical morphology to enhance 3D vessel-like structures in biomedical images. The proposed method, 3D bowler-hat transform, combines sphere and line structuring elements to enhance vessel-l...

  20. Calculating the Jet Transport Coefficient q-hat in Lattice Gauge Theory

    International Nuclear Information System (INIS)

    Majumder, Abhijit

    2013-01-01

    The formalism of jet modification in the higher twist approach is modified to describe a hard parton propagating through a hot thermalized medium. The leading order contribution to the transverse momentum broadening of a high energy (near on-shell) quark in a thermal medium is calculated. This involves a factorization of the perturbative process of scattering of the quark from the non-perturbative transport coefficient. An operator product expansion of the non-perturbative operator product which represents q -hat is carried out and related via dispersion relations to the expectation of local operators. These local operators are then evaluated in quenched SU(2) lattice gauge theory

  1. Transiting Exoplanet Monitoring Project (TEMP). IV. Refined System Parameters, Transit Timing Variations, and Orbital Stability of the Transiting Planetary System HAT-P-25

    Science.gov (United States)

    Wang, Xian-Yu; Wang, Songhu; Hinse, Tobias C.; Li, Kai; Wang, Yong-Hao; Laughlin, Gregory; Liu, Hui-Gen; Zhang, Hui; Wu, Zhen-Yu; Zhou, Xu; Zhou, Ji-Lin; Hu, Shao-Ming; Wu, Dong-Hong; Peng, Xi-Yan; Chen, Yuan-Yuan

    2018-06-01

    We present eight new light curves of the transiting extra-solar planet HAT-P-25b obtained from 2013 to 2016 with three telescopes at two observatories. We use the new light curves, along with recent literature material, to estimate the physical and orbital parameters of the transiting planet. Specifically, we determine the mid-transit times (T C ) and update the linear ephemeris, T C[0] = 2456418.80996 ± 0.00025 [BJDTDB] and P = 3.65281572 ± 0.00000095 days. We carry out a search for transit timing variations (TTVs), and find no significant TTV signal at the ΔT = 80 s-level, placing a limit on the possible strength of planet–planet interactions (TTVG). In the course of our analysis, we calculate the upper mass-limits of the potential nearby perturbers. Near the 1:2, 2:1, and 3:1 resonances with HAT-P-25b, perturbers with masses greater than 0.5, 0.3, and 0.5 M ⊕ respectively, can be excluded. Furthermore, based on the analysis of TTVs caused by light travel time effect (LTTE) we also eliminate the possibility that a long-period perturber exists with M p > 3000 MJ within a = 11.2 au of the parent star.

  2. Assessment of the radiological impact of the inactive uranium-mill tailings at Mexican Hat, Utah

    Energy Technology Data Exchange (ETDEWEB)

    Haywood, F.F.; Goldsmith, W.A.; Ellis, B.S.; Hubbard, H.M. Jr.; Fox, W.F.; Shinpaugh, W.H.

    1980-03-01

    High surface soil concentrations of /sup 226/Ra and high above-ground measurements of gamma-ray intensity in the vicinity of the inactive uranium-mill tailings at Mexican Hat show both wind and water erosion of the tailings. The former mill area, occupied by a trade school at the time of this survey, shows a comparatively high level of contamination, probably from unprocessed ore on the surface of the ore storage area near the location of the former mill buildings. However, the estimated health effect of exposure to gamma rays during a 2000-hr work year in the area represents an increase of 0.1% in the risk of death from cancer. Exposure of less than 600 persons within 1.6 km of the tailings to radon daughters results in an estimated 0.2%/year increase in risk of lung cancer.

  3. Assessment of the radiological impact of the inactive uranium-mill tailings at Mexican Hat, Utah

    International Nuclear Information System (INIS)

    Haywood, F.F.; Goldsmith, W.A.; Ellis, B.S.; Hubbard, H.M. Jr.; Fox, W.F.; Shinpaugh, W.H.

    1980-03-01

    High surface soil concentrations of 226 Ra and high above-ground measurements of gamma-ray intensity in the vicinity of the inactive uranium-mill tailings at Mexican Hat show both wind and water erosion of the tailings. The former mill area, occupied by a trade school at the time of this survey, shows a comparatively high level of contamination, probably from unprocessed ore on the surface of the ore storage area near the location of the former mill buildings. However, the estimated health effect of exposure to gamma rays during a 2000-hr work year in the area represents an increase of 0.1% in the risk of death from cancer. Exposure of less than 600 persons within 1.6 km of the tailings to radon daughters results in an estimated 0.2%/year increase in risk of lung cancer

  4. Insulin stimulates choline acetyltransferase activity in cultured embryonic chicken retina neurons

    International Nuclear Information System (INIS)

    Kyriakis, J.M.; Hausman, R.E.; Peterson, S.W.

    1987-01-01

    The effect of insulin on the appearance of the enzyme choline acetyltransferase in embryonic chicken retina neurons cultured in defined medium was studied. In the presence of a minimal level of insulin (1 ng/ml), ChoAcT activity increased with time in culture. A correspondence between the insulin concentration in the defined medium (1-100 ng/ml) and both the rate of increase and maximum attained level of ChoAcT activity was observed. Maximal ChoAcT activity was 2- to 3-fold greater in cells cultured in the presence of 100 ng of insulin per ml than in cells cultured in the presence of 1 ng of insulin per ml. To elicit maximum ChoAcT activity, insulin at 100 ng/ml was required in the medium for only the first 4 days of the culture period, at which time insulin could be reduced to maintenance levels (10 ng/ml) without affecting ChoAcT activity. Insulin binding assays performed during a 7-day culture period revealed that irrespective of the 125 I-insulin concentration in the medium during culture, cell-surface insulin receptors decreased by ≅ 90% between 4 and 7 days in culture. This decrease in insulin binding corresponded to the observed decrease in the sensitivity of ChoAcT activity to insulin. The findings suggest that insulin plays a role in mediating cholinergic differentiation in the embryonic chicken retina

  5. Description of rainfall variability in Br hat -samhita of Varâha-mihira

    OpenAIRE

    Iyengar, RN

    2004-01-01

    Br hat -samhita of Varâha-mihira (5–6th century AD) provides valuable information on the approach in ancient India towards monsoon rainfall, including its measurement and forecasting. In this context, we come across a description of the expected amount of total seasonal rainfall depending on the first rains under the 27 naks atras of Indian astronomy. This provides a rough statistical picture of what might have been the rainfall and its variability in the region around Ujjain, where Varâha-mi...

  6. The enhancing effect of genistein on apoptosis induced by trichostatin A in lung cancer cells with wild type p53 genes is associated with upregulation of histone acetyltransferase

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Tzu-Chin [Chest Clinic, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Lin, Yi-Chin [Department of Nutritional Science, Chung Shan Medical University, Taichung, Taiwan (China); Chen, Hsiao-Ling [Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China); Huang, Pei-Ru; Liu, Shang-Yu [Department of Nutritional Science, Chung Shan Medical University, Taichung, Taiwan (China); Yeh, Shu-Lan, E-mail: suzyyeh@csmu.edu.tw [Department of Nutritional Science, Chung Shan Medical University, Taichung, Taiwan (China); Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan (China)

    2016-02-01

    Genistein has been shown to enhance the antitumor activity of trichostatin A (TSA) in human lung carcinoma A549 cells. However, whether the combined treatment exerts the same effect in other lung cancer cells is unclear. In the present study we first compared the enhancing effect of genistein on the antitumor effect of TSA in ABC-1, NCI-H460 (H460) and A549 cells. Second, we investigated whether the effects of genistein are associated with increased histone/non-histone protein acetylation. We found that the enhancing effect of genistein on cell-growth-arrest in ABC-1 cells (p53 mutant) was less than in A549 and H460 cells. Genistein enhanced TSA induced apoptosis in A549 and H460 cells rather than in ABC-1 cells. After silencing p53 expression in A549 and H460 cells, the enhancing effect of genistein was diminished. In addition, genistein increased TSA-induced histone H3/H4 acetylation in A549 and H460 cells. Genistein also increased p53 acetylation in H460 cells. The inhibitor of acetyltransferase, anacardic acid, diminished the enhancing effect of genistein on all TSA-induced histone/p53 acetylation and apoptosis. Genistein in combination with TSA increased the expression of p300 protein, an acetyltransferase, in A549 and NCI-H460 cells. Furthermore, we demonstrated that genistein also enhanced the antitumor effect of genistein in A549-tumor-bearing mice. Taken together, these results suggest that the enhancing effects of genistein on TSA-induced apoptosis in lung cancer cells were p53-dependent and were associated with histone/non-histone protein acetylation. - Highlights: • Genistein enhances the antitumor effect of TSA through p53-associated pathways. • Genistein enhances TSA-induced histone acetylation commonly. • An acetyltransferase inhibitor diminishes the antitumor effect of genistein + TSA. • TSA in combination with genistein increases the expression of p300. • Genistein given by i.p. injection increases the antitumor effect of TSA in vivo.

  7. The enhancing effect of genistein on apoptosis induced by trichostatin A in lung cancer cells with wild type p53 genes is associated with upregulation of histone acetyltransferase

    International Nuclear Information System (INIS)

    Wu, Tzu-Chin; Lin, Yi-Chin; Chen, Hsiao-Ling; Huang, Pei-Ru; Liu, Shang-Yu; Yeh, Shu-Lan

    2016-01-01

    Genistein has been shown to enhance the antitumor activity of trichostatin A (TSA) in human lung carcinoma A549 cells. However, whether the combined treatment exerts the same effect in other lung cancer cells is unclear. In the present study we first compared the enhancing effect of genistein on the antitumor effect of TSA in ABC-1, NCI-H460 (H460) and A549 cells. Second, we investigated whether the effects of genistein are associated with increased histone/non-histone protein acetylation. We found that the enhancing effect of genistein on cell-growth-arrest in ABC-1 cells (p53 mutant) was less than in A549 and H460 cells. Genistein enhanced TSA induced apoptosis in A549 and H460 cells rather than in ABC-1 cells. After silencing p53 expression in A549 and H460 cells, the enhancing effect of genistein was diminished. In addition, genistein increased TSA-induced histone H3/H4 acetylation in A549 and H460 cells. Genistein also increased p53 acetylation in H460 cells. The inhibitor of acetyltransferase, anacardic acid, diminished the enhancing effect of genistein on all TSA-induced histone/p53 acetylation and apoptosis. Genistein in combination with TSA increased the expression of p300 protein, an acetyltransferase, in A549 and NCI-H460 cells. Furthermore, we demonstrated that genistein also enhanced the antitumor effect of genistein in A549-tumor-bearing mice. Taken together, these results suggest that the enhancing effects of genistein on TSA-induced apoptosis in lung cancer cells were p53-dependent and were associated with histone/non-histone protein acetylation. - Highlights: • Genistein enhances the antitumor effect of TSA through p53-associated pathways. • Genistein enhances TSA-induced histone acetylation commonly. • An acetyltransferase inhibitor diminishes the antitumor effect of genistein + TSA. • TSA in combination with genistein increases the expression of p300. • Genistein given by i.p. injection increases the antitumor effect of TSA in vivo.

  8. A 82Br tracer study of coastal groundwater movement at Hat Head, NSW

    International Nuclear Information System (INIS)

    Hughes, C.; Stone, D.

    2003-01-01

    At Hat Head, NSW, on the eastern Australian coast, a radioisotope tracer study of groundwater flow in response to tidal forcing was conducted adjacent to a tidal creek. Using radiotracer, 82 Br, groundwater movement was tracked in-situ over 5 days on two occasions encompassing both neap and spring tide conditions. The tracer was injected into one borehole and gamma counts monitored from an adjacent borehole using NaI(Th) detectors. This technique maps the path of the slow moving tracer without sampling and allows the net groundwater movement to be distinguished from short term tidally driven fluxes. During the neap tide period net groundwater movement of 0.1 m/d was observed with horizontal tidal fluctuations in the order of 0.04 m. This contrasts with the tidally dominated spring tide period where net groundwater movement was negligible but tidally driven fluctuations of up to 0.13 m were observed

  9. An Algorithm of Building Extraction in Urban Area Based on Improved Top-hat Transformations and LBP Elevation Texture

    Directory of Open Access Journals (Sweden)

    HE Manyun

    2017-09-01

    Full Text Available Classification of building and vegetation is difficult solely by LiDAR data and vegetation in shadows can't be eliminated only by aerial images. The improved top-hat transformations and local binary patterns (LBP elevation texture analysis for building extraction are proposed based on the fusion of aerial images and LiDAR data. Firstly, LiDAR data is reorganized into grid cell, the algorithm removes ground points through top-hat transform. Then, the vegetation points are extracted by normalized difference vegetation index (NDVI. Thirdly, according to the elevation information of LiDAR points, LBP elevation texture is calculated and achieving precise elimination of vegetation in shadows or surrounding to the buildings. At last, morphological operations are used to fill the holes of building roofs, and region growing for complete building edges. The simulation is based on the complex urban area in Vaihingen benchmark provided by ISPRS, the results show that the algorithm affording higher classification accuracy.

  10. [Relationship between viral load of human bocavirus and clinical characteristics in children with acute lower respiratory tract infection].

    Science.gov (United States)

    Ding, Xiao-Fang; Zhang, Bing; Zhong, Li-Li; Xie, Le-Yun; Xiao, Ni-Guang

    2017-03-01

    To investigate the prevalence of human bocavirus (HBoV) in children with acute lower respiratory tract infection and to explore the relationship between the viral load of HBoV and the clinical characteristics of acute lower respiratory tract infection in children. A total of 1 554 nasopharyngeal aspirates from children who were hospitalized due to acute lower respiratory tract infection between March 2011 and March 2014 were collected. Quantitative real-time PCR was used to detect 12 RNA and 2 DNA viruses, adenovirus (ADV) and HBoV, and to measure the viral load of HBoV in HBoV-positive children. A comprehensive analysis was performed with reference to clinical symptoms and indicators. In the 1 554 specimens, 1 212 (77.99%) were positive for viruses, and 275 (17.70%) were HBoV-positive. In HBoV-positive cases, 94.9% were aged infection, and 230 (83.64%) had mixed infection. There was no significant difference in viral load between children with single infection and mixed infection (P>0.05). The patients with fever had a significantly higher viral load than those without fever (Pacute lower respiratory tract infection (P>0.05). HBoV is one of the important pathogens of acute lower respiratory tract infection in children. Children with a higher viral load of HBoV are more likely to experience symptoms such as fever and wheezing. However, the severity of disease and mixed infection are not significantly related to viral load.

  11. Phylogenic analysis of human bocavirus detected in children with acute respiratory infection in Yaounde, Cameroon.

    Science.gov (United States)

    Kenmoe, Sebastien; Vernet, Marie-Astrid; Njankouo-Ripa, Mohamadou; Penlap, Véronique Beng; Vabret, Astrid; Njouom, Richard

    2017-07-17

    Human Bocavirus (HBoV) was first identified in 2005 and has been shown to be a common cause of respiratory infections and gastroenteritis in children. In a recent study, we found that 10.7% of children with acute respiratory infections (ARI) were infected by HBoV. Genetic characterization of this virus remains unknown in Central Africa, particularly in Cameroon Leeding us to evaluate the molecular characteristics of HBoV strains in Cameroonian children with ARI. Phylogenetic analysis of partial HBoV VP1/2 sequences showed a low level of nucleotide variation and the circulation of HBoV genotype 1 (HBoV-1) only. Three clades were obtained, two clustering with each of the reference strains ST1 and ST2, and a third group consisting of only Cameroon strains. By comparing with the Swedish reference sequences, ST1 and ST2, Cameroon sequences showed nucleotide and amino acid similarities of respectively 97.36-100% and 98.35-100%. These results could help improve strategies for monitoring and control of respiratory infections in Cameroon.

  12. Cigarette Smoking, N-Acetyltransferase 2 Acetylation Status, and Bladder Cancer Risk

    DEFF Research Database (Denmark)

    Marcus, P.M.; Hayes, R.B.; Vineis, P.

    2000-01-01

    Tobacco use is an established cause of bladder cancer. The ability to detoxify aromatic amines, which are present in tobacco and are potent bladder carcinogens, is compromised in persons with the N-acetyltransferase 2 slow acetylation polymorphism. The relationship of cigarette smoking with bladder...... cancer risk therefore has been hypothesized to be stronger among slow acetylators. The few studies to formally explore such a possibility have produced inconsistent results, however. To assess this potential gene-environment interaction in as many bladder cancer studies as possible and to summarize...... results, we conducted a meta-analysis using data from 16 bladder cancer studies conducted in the general population (n = 1999 cases), Most had been conducted in European countries. Because control subjects were unavailable for a number of these studies, we used a case-series design, which can be used...

  13. Logarithmic sℓ-hat (2) CFT models from Nichols algebras: I

    International Nuclear Information System (INIS)

    Semikhatov, A M; Tipunin, I Yu

    2013-01-01

    We construct chiral algebras that centralize rank-2 Nichols algebras with at least one fermionic generator. This gives ‘logarithmic’ W-algebra extensions of a fractional-level sℓ-hat (2) algebra. We discuss crucial aspects of the emerging general relation between Nichols algebras and logarithmic conformal field theory (CFT) models: (i) the extra input, beyond the Nichols algebra proper, needed to uniquely specify a conformal model; (ii) a relation between the CFT counterparts of Nichols algebras connected by Weyl groupoid maps; and (iii) the common double bosonization U(X) of such Nichols algebras. For an extended chiral algebra, candidates for its simple modules that are counterparts of the U(X) simple modules are proposed, as a first step toward a functorial relation between U(X) and W-algebra representation categories. (paper)

  14. Spin Triplet Nematic Pairing Symmetry and Superconducting Double Transition in U1-xThxBe13

    Science.gov (United States)

    Machida, Kazushige

    2018-03-01

    Motivated by a recent experiment on U1-xThxBe13 with x = 3%, we develop a theory to narrow down the possible pair symmetry to consistently describe the double transition utilizing various theoretical tools, including group theory and Ginzburg-Landau theory. It is explained in terms of the two-dimensional representation Eu with spin triplet. Symmetry breaking causes the degenerate Tc to split into two. The low-temperature phase is identified as the cyclic p wave: d(k) = \\hat{x}kx + ɛ \\hat{y}ky + ɛ 2\\hat{z}kz with ɛ3 = 1, whereas the biaxial nematic phase: d(k) = √{3} (\\hat{x}kx - \\hat{y}ky) is the high-temperature one. This allows us to simultaneously identify the uniaxial nematic phase: d(k) = 2\\hat{z}kz - \\hat{x}kx - \\hat{y}ky for UBe13, which spontaneously breaks the cubic symmetry of the system. Those pair functions are fully consistent with this description and existing data. We comment on the accidental scenario in addition to this degeneracy scenario and the intriguing topological nature hidden in this long-known material.

  15. Antifungal Activity of Phenyl Derivative of Pyranocoumarin from Psoralea corylifolia L. Seeds by Inhibition of Acetylation Activity of Trichothecene 3-O-Acetyltransferase (Tri101

    Directory of Open Access Journals (Sweden)

    Sangeetha Srinivasan

    2012-01-01

    Full Text Available Antifungal activity of petroleum ether extract of Psoralea corylifolia L. seed, tested against Fusarium sp. namely, Fusarium oxysporum, Fusarium moniliforme, and Fusarium graminearum, was evaluated by agar well diffusion assay. The chromatographic fractionation of the extract yielded a new phenyl derivative of pyranocoumarin (PDP. The structure of the PDP was confirmed using spectroscopic characterization (GC-MS, IR, and NMR, and a molecular mass of m/z 414 [M-2H]+ with molecular formula C27H28O4 was obtained. The PDP had a potent antifungal activity with a minimum inhibitory concentration of 1 mg/mL against Fusarium sp. Molecular docking using Grid-Based Ligand Docking with Energetics (GLIDE, Schrodinger was carried out with the Tri101, trichothecene 3-O-acetyltransferase, as target protein to propose a mechanism for the antifungal activity. The ligand PDP showed bifurcated hydrogen bond interaction with active site residues at TYR 413 and a single hydrogen bond interaction at ARG 402 with a docking score −7.19 and glide energy of −45.78 kcal/mol. This indicated a strong binding of the ligand with the trichothecene 3-O-acetyltransferase, preventing as a result the acetylation of the trichothecene mycotoxin and destruction of the “self-defense mechanism” of the Fusarium sp.

  16. Synergistic inhibitory effect of hyperbaric oxygen combined with sorafenib on hepatoma cells.

    Directory of Open Access Journals (Sweden)

    Hai-Shan Peng

    Full Text Available OBJECTIVES: Hypoxia is a common phenomenon in solid tumors, associated with chemotherapy and radiotherapy resistance, recurrence and metastasis. Hyperbaric oxygen (HBO therapy can increase tissue oxygen pressure and content to prevent the resistance, recurrence and metastasis of cancer. Presently, Sorafenib is a first-line drug, targeted for hepatocellular carcinoma (HCC but effective in only a small portion of patients and can induce hypoxia. The purpose of this study is to investigate the effect of HBO in combination with sorafenib on hepatoma cells. METHODS: Hepatoma cell lines (BEL-7402 and SK-Hep1 were treated with HBO at 2 atmosphere absolute pressure for 80 min per day or combined with sorafenib or cisplatin. At different time points, cells were tested for cell growth, colony formation, apoptosis, cell cycle and migration. Finally, miRNA from the hepatoma cells was detected by microRNA array and validated by qRT-PCR. RESULTS: Although HBO, sorafenib or cisplatin alone could inhibit growth of hepatoma cells, HBO combined with sorafenib or cisplatin resulted in much greater synergistic growth inhibition (cell proliferation and colony formation in hepatoma cells. Similarly, the synergistic effect of HBO and sorafenib on induction of apoptosis was also observed in hepatoma cells. HBO induced G1 arrest in SK-Hep1 not in BEL-7402 cells, but enhanced cell cycle arrest induced by sorafenib in BEL-7402 treated cells. However, HBO had no obvious effect on the migration of hepatoma cells, and microRNA array analysis showed that hepatoma cells with HBO treatment had significantly different microRNA expression profiles from those with blank control. CONCLUSIONS: We show for the first time that HBO combined with sorafenib results in synergistic growth inhibition and apoptosis in hepatoma cells, suggesting a potential application of HBO combined with sorafenib in HCC patients. Additionally, we also show that HBO significantly altered microRNA expression

  17. The Discovery of Ellipsoidal Variations in the Kepler Light Curve of HAT-P-7

    OpenAIRE

    Welsh, William F.; Orosz, Jerome A.; Seager, Sara; Fortney, Jonathan J.; Jenkins, Jon; Rowe, Jason F.; Koch, David; Borucki, William J.

    2010-01-01

    We present an analysis of the early Kepler observations of the previously discovered transiting planet HAT-P-7b. The light curve shows the transit of the star, the occultation of the planet, and the orbit phase-dependent light from the planet. In addition, phase-dependent light from the star is present, known as "ellipsoidal variations". The very nearby planet (only 4 stellar radii away) gravitationally distorts the star and results in a flux modulation twice per orbit. The ellipsoidal variat...

  18. Effects of hyperbaric oxygen therapy in enhancing expressions of e-NOS, TNF-α and VEGF in wound healing

    Science.gov (United States)

    Susilo, Imam; Devi, Anita; Purwandhono, Azham; Hadi Warsito, Sunaryo

    2017-05-01

    Wound healing is a physiological process that occurs progressively through overlapping phases. Tissue oxygenation is an important part of the complex regulation for wound healing. Hyperbaric Oxygen (HBO) therapy is a method of increasing oxygen delivery to tissues. The therapy improves tissue oxygenation and stimulates the formation of H2O2 as a secondary messenger for Tumour Necrosis Factor alpha (TNF α), e-NOS, VEGF and Nuclear Factor Kappa Beta phosphorylation (NF-Kb) which play an important role in the rapid transcription of a wide variety of genes in response to extracellular stimuli. This study aims to determine the effects of Hyperbaric Oxygen therapy in enhancing the expressions of e-NOS, TNF-α, VEGF and wound healing. This study is an animal study with a ‘randomized control group of pre-test and post test design’ on 28 Wistar rats. Randomly, the rats were divided into 4 groups with 7 rats in each group. The HBO treatment group 1 received 5 sessions of HBO 2.4 ATA in 3 × 30 minutes; the HBO treatment group 2 received 10 sessions of HBO 2.4 ATA in 3 × 30 minutes; and each of the control groups were without HBO. Each of the 28 male rats were given a full thickness excisional wound of 1 × 1cm. Examinations of e-NOS, TNF-α, VEGF expressions and wound healing were performed on day-0 (pre-HBO) and day-5 HBO or on day-0 (pre-HBO) and day-10 HBO. The resultsshowthat the Hyperbaric Oxygen therapy can improve e-NOS (p=0.02), TNF-α (p= 0.02), VEGF expression (p=0.02) and wound healing (p=0.002) significantly in the provision of HBO 2.4 ATA for 3 × 30 minutes in 5 sessions over 5 consecutive days. While the 10 sessions of HBO 2.4 ATA for 3 × 30 minutes over 10 consecutive days only increase e-NOS (p=0.02), TNF-α (p=0.04), VEGF expression significantly (p=0.03) but do not improve wound healing significantly (p=0.3) compared with no HBO. The study concludes that HBO can improve the expressions of e-NOS, TNF-α, VEGF and wound healing in the provision of HBO

  19. Effect of prophylactic hyperbaric oxygen treatment for radiation-induced brain injury after stereotactic radiosurgery of brain metastases

    International Nuclear Information System (INIS)

    Ohguri, Takayuki; Imada, Hajime; Kohshi, Kiyotaka; Kakeda, Shingo; Ohnari, Norihiro; Morioka, Tomoaki; Nakano, Keita; Konda, Nobuhide; Korogi, Yukunori

    2007-01-01

    Purpose: The purpose of the present study was to evaluate the prophylactic effect of hyperbaric oxygen (HBO) therapy for radiation-induced brain injury in patients with brain metastasis treated with stereotactic radiosurgery (SRS). Methods and Materials: The data of 78 patients presenting with 101 brain metastases treated with SRS between October 1994 and September 2003 were retrospectively analyzed. A total of 32 patients with 47 brain metastases were treated with prophylactic HBO (HBO group), which included all 21 patients who underwent subsequent or prior radiotherapy and 11 patients with common predictors of longer survival, such as inactive extracranial tumors and younger age. The other 46 patients with 54 brain metastases did not undergo HBO (non-HBO group). Radiation-induced brain injuries were divided into two categories, white matter injury (WMI) and radiation necrosis (RN), on the basis of imaging findings. Results: Radiation-induced brain injury occurred in 5 lesions (11%) in the HBO group (2 WMIs and 3 RNs) and in 11 (20%) in the non-HBO group (9 WMIs and 2 RNs). The WMI was less frequent for the HBO group than for the non-HBO group (p = 0.05), although multivariate analysis by logistic regression showed that WMI was not significantly correlated with HBO (p = 0.07). The 1-year actuarial probability of WMI was significantly better for the HBO group (2%) than for the non-HBO group (36%) (p < 0.05). Conclusions: The present study showed a potential value of prophylactic HBO for Radiation-induced WMIs, which justifies further evaluation to confirm its definite benefit

  20. ANALYSIS OF SPIN-ORBIT ALIGNMENT IN THE WASP-32, WASP-38, AND HAT-P-27/WASP-40 SYSTEMS

    Energy Technology Data Exchange (ETDEWEB)

    Brown, D. J. A.; Collier Cameron, A.; Enoch, B.; Miller, G. R. M. [SUPA, School of Physics and Astronomy, University of St Andrews, North Haugh, St Andrews, Fife KY16 9SS (United Kingdom); Diaz, R. F. [LAM (Laboratoire d' Astrophysique de Marseille), Aix Marseille Universite, CNRS, UMR 7326, F-13388 Marseille (France); Doyle, A. P.; Smalley, B.; Anderson, D. R.; Hellier, C.; Maxted, P. F. L. [Astrophysics Group, School of Physical and Geographical Sciences, Lennard-Jones Building, Keele University, Staffordshire ST5 5BG (United Kingdom); Gillon, M. [Institut d' Astrophysique et de Geophysique, Universite de Liege, Allee du 6 Aout, 17 (Bat. B5C) Sart Tilman, B-4000 Liege (Belgium); Lendl, M.; Triaud, A. H. M. J.; Queloz, D. [Observatoire Astronomique de l' Universite de Geneve, 51 Chemin des Maillettes, CH-1290 Sauverny (Switzerland); Pollacco, D. [Astrophysics Research Centre, School of Mathematics and Physics, Queen' s University, University Road, Belfast BT7 1NN (United Kingdom); Boisse, I. [Centro de Astrofisica, Universidade do Porto, Rua das Estrelas, 4150-762 Porto (Portugal); Hebrard, G., E-mail: djab@st-andrews.ac.uk [Institut dAstrophysique de Paris, UMR7095 CNRS, Universite Pierre and Marie Curie, 98bis boulevard Arago, F-75014 Paris (France)

    2012-12-01

    We present measurements of the spin-orbit alignment angle, {lambda}, for the hot Jupiter systems WASP-32, WASP-38, and HAT-P-27/WASP-40, based on data obtained using the HARPS spectrograph. We analyze the Rossiter-McLaughlin effect for all three systems and also carry out Doppler tomography for WASP-32 and WASP-38. We find that WASP-32 (T {sub eff} = 6140{sup +90} {sub -100} K) is aligned, with an alignment angle of {lambda} = 10.{sup 0}5{sup +6.4} {sub -6.5} obtained through tomography, and that WASP-38 (T {sub eff} = 6180{sup +40} {sub -60} K) is also aligned, with tomographic analysis yielding {lambda} = 7.{sup 0}5{sup +4.7} {sub -6.1}. The latter result provides an order-of-magnitude improvement in the uncertainty in {lambda} compared to the previous analysis of Simpson et al. We are only able to loosely constrain the angle for HAT-P-27/WASP-40 (T{sub eff} = 5190{sup +160} {sub -170} K) to {lambda} = 24.{sup 0}2{sup +76.0}{sub -44.5}, owing to the poor signal-to-noise ratio of our data. We consider this result a non-detection under a slightly updated version of the alignment test of Brown et al. We place our results in the context of the full sample of spin-orbit alignment measurements, finding that they provide further support for previously established trends.

  1. Does human bocavirus infection depend on helper viruses? A challenging case report

    Directory of Open Access Journals (Sweden)

    Brockmann Michael

    2011-08-01

    Full Text Available Abstract A case of severe diarrhoea associated with synergistic human bocavirus type 1 (HBoV and human herpes virus type 6 (HHV6 is reported. The case supports the hypotheses that HBoV infection under clinical conditions may depend on helper viruses, or that HBoV replicates by a mechanism that is atypical for parvoviruses, or that HBoV infection can be specifically treated with cidofovir.

  2. Transcriptional Adaptor ADA3 of Drosophila melanogaster Is Required for Histone Modification, Position Effect Variegation, and Transcription▿ †

    OpenAIRE

    Grau, Benjamin; Popescu, Cristina; Torroja, Laura; Ortuño-Sahagún, Daniel; Boros, Imre; Ferrús, Alberto

    2007-01-01

    The Drosophila melanogaster gene diskette (also known as dik or dAda3) encodes a protein 29% identical to human ADA3, a subunit of GCN5-containing histone acetyltransferase (HAT) complexes. The fly dADA3 is a major contributor to oogenesis, and it is also required for somatic cell viability. dADA3 localizes to chromosomes, and it is significantly reduced in dGcn5 and dAda2a, but not in dAda2b, mutant backgrounds. In dAda3 mutants, acetylation at histone H3 K9 and K14, but not K18, and at hist...

  3. The man who mistook his wife for a hat

    CERN Document Server

    Sacks, Oliver

    2011-01-01

    Oliver Sacks’s The Man Who Mistook His Wife for a Hat tells the stories of individuals afflicted with fantastic perceptual and intellectual aberrations: patients who have lost their memories and with them the greater part of their pasts; who are no longer able to recognize people and common objects; who are stricken with violent tics and grimaces or who shout involuntary obscenities; whose limbs have become alien; who have been dismissed as retarded yet are gifted with uncanny artistic or mathematical talents. If inconceivably strange, these brilliant tales remain, in Dr. Sacks’s splendid and sympathetic telling, deeply human. They are studies of life struggling against incredible adversity, and they enable us to enter the world of the neurologically impaired, to imagine with our hearts what it must be to live and feel as they do. A great healer, Sacks never loses sight of medicine’s ultimate responsibility: “the suffering, afflicted, fighting human subject.”

  4. Quercetin suppresses cyclooxygenase-2 expression and angiogenesis through inactivation of P300 signaling.

    Directory of Open Access Journals (Sweden)

    Xiangsheng Xiao

    Full Text Available Quercetin, a polyphenolic bioflavonoid, possesses multiple pharmacological actions including anti-inflammatory and antitumor properties. However, the precise action mechanisms of quercetin remain unclear. Here, we reported the regulatory actions of quercetin on cyclooxygenase-2 (COX-2, an important mediator in inflammation and tumor promotion, and revealed the underlying mechanisms. Quercetin significantly suppressed COX-2 mRNA and protein expression and prostaglandin (PG E(2 production, as well as COX-2 promoter activation in breast cancer cells. Quercetin also significantly inhibited COX-2-mediated angiogenesis in human endothelial cells in a dose-dependent manner. The in vitro streptavidin-agarose pulldown assay and in vivo chromatin immunoprecipitation assay showed that quercetin considerably inhibited the binding of the transactivators CREB2, C-Jun, C/EBPβ and NF-κB and blocked the recruitment of the coactivator p300 to COX-2 promoter. Moreover, quercetin effectively inhibited p300 histone acetyltransferase (HAT activity, thereby attenuating the p300-mediated acetylation of NF-κB. Treatment of cells with p300 HAT inhibitor roscovitine was as effective as quercetin at inhibiting p300 HAT activity. Addition of quercetin to roscovitine-treated cells did not change the roscovitine-induced inhibition of p300 HAT activity. Conversely, gene delivery of constitutively active p300 significantly reversed the quercetin-mediated inhibition of endogenous HAT activity. These results indicate that quercetin suppresses COX-2 expression by inhibiting the p300 signaling and blocking the binding of multiple transactivators to COX-2 promoter. Our findings therefore reveal a novel mechanism of action of quercetin and suggest a potential use for quercetin in the treatment of COX-2-mediated diseases such as breast cancers.

  5. The Spt-Ada-Gcn5 Acetyltransferase (SAGA complex in Aspergillus nidulans.

    Directory of Open Access Journals (Sweden)

    Paraskevi Georgakopoulos

    Full Text Available A mutation screen in Aspergillus nidulans uncovered mutations in the acdX gene that led to altered repression by acetate, but not by glucose. AcdX of A. nidulans is highly conserved with Spt8p of Saccharomyces cerevisiae, and since Spt8p is a component of the Spt-Ada-Gcn5 Acetyltransferase (SAGA complex, the SAGA complex may have a role in acetate repression in A. nidulans. We used a bioinformatic approach to identify genes encoding most members of the SAGA complex in A. nidulans, and a proteomic analysis to confirm that most protein components identified indeed exist as a complex in A. nidulans. No apparent compositional differences were detected in mycelia cultured in acetate compared to glucose medium. The methods used revealed apparent differences between Yeast and A. nidulans in the deubiquitination (DUB module of the complex, which in S. cerevisiae consists of Sgf11p, Sus1p, and Ubp8p. Although a convincing homologue of S. cerevisiae Ubp8p was identified in the A. nidulans genome, there were no apparent homologues for Sus1p and Sgf11p. In addition, when the SAGA complex was purified from A. nidulans, members of the DUB module were not co-purified with the complex, indicating that functional homologues of Sus1p and Sgf11p were not part of the complex. Thus, deubiquitination of H2B-Ub in stress conditions is likely to be regulated differently in A. nidulans compared to S. cerevisiae.

  6. Nuclear 82-kDa choline acetyltransferase decreases amyloidogenic APP metabolism in neurons from APP/PS1 transgenic mice.

    Science.gov (United States)

    Albers, Shawn; Inthathirath, Fatima; Gill, Sandeep K; Winick-Ng, Warren; Jaworski, Ewa; Wong, Daisy Y L; Gros, Robert; Rylett, R Jane

    2014-09-01

    Alzheimer disease (AD) is associated with increased amyloidogenic processing of amyloid precursor protein (APP) to β-amyloid peptides (Aβ), cholinergic neuron loss with decreased choline acetyltransferase (ChAT) activity, and cognitive dysfunction. Both 69-kDa ChAT and 82-kDa ChAT are expressed in cholinergic neurons in human brain and spinal cord with 82-kDa ChAT localized predominantly to neuronal nuclei, suggesting potential alternative functional roles for the enzyme. By gene microarray analysis, we found that 82-kDa ChAT-expressing IMR32 neural cells have altered expression of genes involved in diverse cellular functions. Importantly, genes for several proteins that regulate APP processing along amyloidogenic and non-amyloidogenic pathways are differentially expressed in 82-kDa ChAT-containing cells. The predicted net effect based on observed changes in expression patterns of these genes would be decreased amyloidogenic APP processing with decreased Aβ production. This functional outcome was verified experimentally as a significant decrease in BACE1 protein levels and activity and a concomitant reduction in the release of endogenous Aβ1-42 from neurons cultured from brains of AD-model APP/PS1 transgenic mice. The expression of 82-kDa ChAT in neurons increased levels of GGA3, which is involved in trafficking BACE1 to lysosomes for degradation. shRNA-induced decreases in GGA3 protein levels attenuated the 82-kDa ChAT-mediated decreases in BACE1 protein and activity and Aβ1-42 release. Evidence that 82-kDa ChAT can enhance GGA3 gene expression is shown by enhanced GGA3 gene promoter activity in SN56 neural cells expressing this ChAT protein. These studies indicate a novel relationship between cholinergic neurons and APP processing, with 82-kDa ChAT acting as a negative regulator of Aβ production. This decreased formation of Aβ could result in protection for cholinergic neurons, as well as protection of other cells in the vicinity that are sensitive to

  7. Co-expression of G2-EPSPS and glyphosate acetyltransferase GAT genes conferring high tolerance to glyphosate in soybean

    OpenAIRE

    Guo, Bingfu; Guo, Yong; Hong, Huilong; Jin, Longguo; Zhang, Lijuan; Chang, Ru-Zhen; Lu, Wei; Lin, Min; Qiu, Li-Juan

    2015-01-01

    Glyphosate is a widely used non-selective herbicide with broad spectrum of weed control around the world. At present, most of the commercial glyphosate tolerant soybeans utilize glyphosate tolerant gene CP4-EPSPS or glyphosate acetyltransferase gene GAT separately. In this study, both glyphosate tolerant gene G2-EPSPS and glyphosate degraded gene GAT were co-transferred into soybean and transgenic plants showed high tolerance to glyphosate. Molecular analysis including PCR, Sothern blot, qRT-...

  8. Structures of the N-acetyltransferase domain of Xylella fastidiosa N-acetyl-L-glutamate synthase/kinase with and without a His tag bound to N-acetyl-L-glutamate.

    Science.gov (United States)

    Zhao, Gengxiang; Jin, Zhongmin; Allewell, Norma M; Tuchman, Mendel; Shi, Dashuang

    2015-01-01

    Structures of the catalytic N-acetyltransferase (NAT) domain of the bifunctional N-acetyl-L-glutamate synthase/kinase (NAGS/K) from Xylella fastidiosa bound to N-acetyl-L-glutamate (NAG) with and without an N-terminal His tag have been solved and refined at 1.7 and 1.4 Å resolution, respectively. The NAT domain with an N-terminal His tag crystallized in space group P4(1)2(1)2, with unit-cell parameters a=b=51.72, c=242.31 Å. Two subunits form a molecular dimer in the asymmetric unit, which contains ∼41% solvent. The NAT domain without an N-terminal His tag crystallized in space group P21, with unit-cell parameters a=63.48, b=122.34, c=75.88 Å, β=107.6°. Eight subunits, which form four molecular dimers, were identified in the asymmetric unit, which contains ∼38% solvent. The structures with and without the N-terminal His tag provide an opportunity to evaluate how the His tag affects structure and function. Furthermore, multiple subunits in different packing environments allow an assessment of the plasticity of the NAG binding site, which might be relevant to substrate binding and product release. The dimeric structure of the X. fastidiosa N-acetytransferase (xfNAT) domain is very similar to that of human N-acetyltransferase (hNAT), reinforcing the notion that mammalian NAGS is evolutionally derived from bifunctional bacterial NAGS/K.

  9. Comparison of the effects of 665 nm low level diode Laser Hat versus and a combination of 665 nm and 808nm low level diode Laser Scanner of hair growth in androgenic alopecia.

    Science.gov (United States)

    Barikbin, Behrooz; Khodamrdi, Zeinab; Kholoosi, Leila; Akhgri, Mohammad Reza; Haj Abbasi, Majid; Hajabbasi, Mojgan; Razzaghi, Zahra; Akbarpour, Samaneh

    2017-05-17

    This study aimed to evaluate the effectiveness of a combined set of low level diode laser scanner (665 nm and 808nm) on hair growth, and assessment of safety and effectiveness of a new laser scanner on hair growth treatment procedure in androgenic alopecia. 90 patients (18 to 70 years) with androgenic alopecia were randomized into three groups. The first group (n=30) received 655 nm red light using laser hat, the second group (n=30) received 655 nm red laser plus 808 nm infrared laser using a laser scanner of hair growth device (with the patent number: 77733) and the third group (n=30) received no laser as the control group. Patients in laser scanner group had better results and showed a higher increase in terminal hair density compared with laser hat group (mean of 9.61 versus 9.16 per cm 2 ). We found significant decrease in terminal hair density from baseline in control group (mean -1.8 per cm 2 , plaser scanner of the hair growth group compared with laser hat and the control group. The study showed that treatment with new laser devise had a promising result without any observable adverse effects.

  10. Spherical top-hat collapse of a viscous unified dark fluid

    Energy Technology Data Exchange (ETDEWEB)

    Li, Wei [Bohai University, Department of Physics, Jinzhou (China); Dalian University of Technology, Institute of Theoretical Physics, Dalian (China); Xu, Lixin [Dalian University of Technology, Institute of Theoretical Physics, Dalian (China)

    2014-05-15

    In this paper, we test the spherical collapse of a viscous unified dark fluid (VUDF) which has constant adiabatic sound speed and show the nonlinear collapse for VUDF, baryons, and darkmatter, which are important in forming the large-scale structure of our Universe. By varying the values of the model parameters α and ζ{sub 0}, we discuss their effects on the nonlinear collapse of the VUDF model, and we compare its result to the ΛCDM model. The results of the analysis show that, within the spherical top-hat collapse framework, larger values of α and smaller values of ζ{sub 0} make the structure formation earlier and faster, and the other collapse curves are almost distinguished with the curve of ΛCDM model if the bulk viscosity coefficient ζ{sub 0} is less than 10{sup -3}. (orig.)

  11. Histone deacetylase 2 is decreased in peripheral blood pro-inflammatory CD8+ T and NKT-like lymphocytes following lung transplant.

    Science.gov (United States)

    Hodge, Greg; Hodge, Sandra; Holmes-Liew, Chien-Li; Reynolds, Paul N; Holmes, Mark

    2017-02-01

    Immunosuppression therapy following lung transplantation fails to prevent chronic rejection in many patients, which is associated with lack of suppression of cytotoxic mediators and pro-inflammatory cytokines in peripheral blood T and natural killer T (NKT)-like cells. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) upregulate/downregulate pro-inflammatory gene expression, respectively; however, differences in the activity of these enzymes following lung transplant are unknown. We hypothesized decreased HDAC2 expression and increased HAT expression in pro-inflammatory lymphocytes following lung transplant. Blood was collected from 18 stable lung transplant patients and 10 healthy age-matched controls. Intracellular pro-inflammatory cytokines and HAT/HDAC2 expression were determined in lymphocyte subsets following culture using flow cytometry. A loss of HDAC2 in cluster of differentiation (CD) 8+ T and NKT-like cells in transplant patients compared with controls was noted (CD8+ T: 28 ± 10 (45 ± 10), CD8+NKT-like: 30 ± 13 (54 ± 16) (mean ± SD transplant) (control)). Loss of HDAC2 was associated with an increased percentage of CD8+ T and NKT-like cells expressing perforin, granzyme b, interferon gamma (IFN-γ) and TNF-α (no change in HAT expression in any lymphocyte subset). There was a negative correlation between loss of HDAC2 expression by CD8+ T cells with cumulative dose of prednisolone and time post-transplant. Treatment with 10 mg/L theophylline + 1 µmol/L prednisolone or 2.5 ng/mL cyclosporine A synergistically upregulated HDAC2 and inhibited IFN-γ and TNF-α production by CD8+ T and NKT-like lymphocytes. HDAC2 is decreased in CD8+ T and NKT-like pro-inflammatory lymphocytes following lung transplant. Treatment options that increase HDAC2 may improve graft survival. © 2016 Asian Pacific Society of Respirology.

  12. Structural analysis of PseH, the Campylobacter jejuni N-acetyltransferase involved in bacterial O-linked glycosylation

    Energy Technology Data Exchange (ETDEWEB)

    Song, Wan Seok; Nam, Mi Sun; Namgung, Byeol [Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Yoon, Sung-il, E-mail: sungil@kangwon.ac.kr [Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701 (Korea, Republic of)

    2015-03-20

    Campylobacter jejuni is a bacterium that uses flagella for motility and causes worldwide acute gastroenteritis in humans. The C. jejuni N-acetyltransferase PseH (cjPseH) is responsible for the third step in flagellin O-linked glycosylation and plays a key role in flagellar formation and motility. cjPseH transfers an acetyl group from an acetyl donor, acetyl coenzyme A (AcCoA), to the amino group of UDP-4-amino-4,6-dideoxy-N-acetyl-β-L-altrosamine to produce UDP-2,4-diacetamido-2,4,6-trideoxy-β-L-altropyranose. To elucidate the catalytic mechanism of cjPseH, crystal structures of cjPseH alone and in complex with AcCoA were determined at 1.95 Å resolution. cjPseH folds into a single-domain structure of a central β-sheet decorated by four α-helices with two continuously connected grooves. A deep groove (groove-A) accommodates the AcCoA molecule. Interestingly, the acetyl end of AcCoA points toward an open space in a neighboring shallow groove (groove-S), which is occupied by extra electron density that potentially serves as a pseudosubstrate, suggesting that the groove-S may provide a substrate-binding site. Structure-based comparative analysis suggests that cjPseH utilizes a unique catalytic mechanism of acetylation that has not been observed in other glycosylation-associated acetyltransferases. Thus, our studies on cjPseH will provide valuable information for the design of new antibiotics to treat C. jejuni-induced gastroenteritis. - Highlights: • cjPseH adopts a single-domain structure of a central β-sheet decorated by α-helices. • cjPseH features two continuously connected grooves on the protein surface. • Acetyl coenzyme A (AcCoA) binds into a deep groove of cjPseH in an ‘L’ shape. • The acetyl end of AcCoA points to a wide groove, a potential substrate-binding site.

  13. Frequency and clinical relevance of human bocavirus infection in acute exacerbations of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Felix C Ringshausen

    2009-02-01

    Full Text Available Felix C Ringshausen1, Ai-Yui M Tan1, Tobias Allander2, Irmgard Borg1, Umut Arinir1, Juliane Kronsbein1, Barbara M Hauptmeier1, Gerhard Schultze-Werninghaus1, Gernot Rohde11Clinical Research Group “Significance of viral infections in chronic respiratory diseases of children and adults,” University Hospital Bergmannsheil, Department of Internal Medicine III–Pneumology, Allergology and Sleep Medicine, Bochum, Germany; 2Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, and Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, SwedenObjective: Human bocavirus (HBoV is a recently discovered parvovirus associated with acute respiratory tract infections in children. The objective of the present study was to determine the frequency and clinical relevance of HBoV infection in adult patients with acute exacerbation of chronic obstructive pulmonary disease (AE-COPD.Methods: We retrospectively tested 212 COPD patients, 141 (66.5% with AE-COPD and 71 (33.5% with stable disease, of whom nasal lavage and induced sputum had been obtained for the presence of HBoV deoxyribonucleic acid (DNA. The specificity of positive polymerase chain reaction results was confirmed by sequencing.Results: Two hundred two of 212 patients for whom PCR results were available both for nasal lavage and induced sputum samples were eligible for data analysis. HBoV DNA was detected in three patients (1.5%. Of those, only one patient had AE-COPD. Thus, the frequency of HBoV infection demonstrated to be low in both AE-COPD (0.8% and stable COPD (2.9%. HBoV was found in two sputum and one nasal lavage sample in different patients, respectively. Sequencing revealed >99% sequence identity with the reference strain.Conclusion: HBoV detection was infrequent. Since we detected HBoV in both upper and lower respiratory tract specimens and in AE-COPD as well as stable disease, a major role of HBoV infection in adults with AE-COPD is unlikely

  14. Enhanced B-Raf-mediated NRF2 gene transcription and HATs-mediated NRF2 protein acetylation contributes to ABCC1-mediated chemoresistance and glutathione-mediated survival in acquired topoisomerase II poison-resistant cancer cells.

    Science.gov (United States)

    Chen, Huang-Hui; Chang, Hsin-Huei; Chang, Jang-Yang; Tang, Ya-Chu; Cheng, Yung-Chi; Lin, Li-Mei; Cheng, Shu-Ying; Huang, Chih-Hsiang; Sun, Man-Wu; Chen, Chiung-Tong; Kuo, Ching-Chuan

    2017-12-01

    Nuclear factor erythroid-2-related factor 2 (NRF2) mainly regulates transcriptional activation through antioxidant-responsive elements (AREs) present in the promoters of NRF2 target genes. Recently, we found that NRF2 was overexpressed in a KB-derived drug-resistant cancer cell panel. In this panel, KB-7D cells, which show acquired resistance to topoisomerase II (Top II) poisons, exhibited the highest NRF2 activation. To investigate whether NRF2 directly contributed to acquired resistance against Top II poisons, we manipulated NRF2 by genetic and pharmacological approaches. The result demonstrated that silencing of NRF2 by RNA interference increased the sensitivity and treatment with NRF2 activator decreased the sensitivity of KB and KB-7D cells toward Top II poisons. Further, increased B-Raf-mediated NRF2 gene transcription and HATs-mediated NRF2 protein acetylation activated NRF2 signaling in KB-7D cells. Moreover, increased binding of NRF2 to an ARE in the promoter of ATP-binding cassette subfamily C member 1 (ABCC1) directly contributed to Top II poison resistance. In addition, activation of NRF2 increased glutathione level and antioxidant capacity in KB-7D cells compared with that in KB cells; moreover, high glutathione level provided survival advantage to KB-7D cells. Our study is the first to show that aberrant NRF2 activation is via increased B-Raf-mediated NRF2 gene transcription and HATs-mediated NRF2 protein acetylation, which increases the acquired resistance and promote the survival of Top II poison-resistant cancer cells. Importantly, NRF2 downstream effectors ABCC1 and glutathione directly contribute to acquired resistance and survival, respectively. These results suggest that blockade of NRF2 signaling may enhance therapeutic efficacy and reduce the survival of Top II poison-refractory tumors in clinical. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Andrographolide: A potent antituberculosis compound that targets Aminoglycoside 2'-N-acetyltransferase in Mycobacterium tuberculosis.

    Science.gov (United States)

    Prabu, Amudha; Hassan, Sameer; Prabuseenivasan; Shainaba, A S; Hanna, L E; Kumar, Vanaja

    2015-09-01

    Tuberculosis (TB) still remains a major challenging infectious disease. The increased rate of emergence of multi-drug resistant and extensively-drug resistant strains of the organism has further complicated the situation, resulting in an urgent need for new anti-TB drugs. Antimycobacterial activity of Andrographis paniculata was evaluated using a rapid LRP assay and the probable targets were identified by docking analysis. The methanolic extract of A. paniculata showed maximum antimycobacterial activity at 250μg/ml against all the tested strains of M. tuberculosis (H37Rv, MDR, and drug sensitive). Based on bioassay guided fractionation, andrographolide was identified as the potent molecule. With the docking analysis, both ICDH (Isocitrate Dehydrogenase) and AAC (Aminoglycoside 2'-N-acetyltransferase) were predicted as targets of andrographolide in M. tuberculosis. Molecular simulation revealed that, ICDH showed low binding affinity to andrographolide. However, for AAC, the andrographolide was observed to be well within the active site after 10ns of molecular simulation. This suggests that ACC (PDB ID 1M4I) could be the probable target for andrographolide. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Adoption of open source software in business models: a Red Hat and IBM case study

    CSIR Research Space (South Africa)

    Munga, N

    2009-10-01

    Full Text Available and its position in the market identified [15]. Various types of business models are discussed in the literature. Rappa [16], using the customer relationship as the primary dimension, defines the brokerage model, information intermediary model... is growing at twice the rate of the platform business [29]. The Market After years of trying to sell to the individual consumer market, Red Hat decided to follow the money and focus its efforts on the enterprise market. The enterprise business customers...

  17. Metabolic Regulation of Histone Acetyltransferases by Endogenous Acyl-CoA Cofactors.

    Science.gov (United States)

    Montgomery, David C; Sorum, Alexander W; Guasch, Laura; Nicklaus, Marc C; Meier, Jordan L

    2015-08-20

    The finding that chromatin modifications are sensitive to changes in cellular cofactor levels potentially links altered tumor cell metabolism and gene expression. However, the specific enzymes and metabolites that connect these two processes remain obscure. Characterizing these metabolic-epigenetic axes is critical to understanding how metabolism supports signaling in cancer, and developing therapeutic strategies to disrupt this process. Here, we describe a chemical approach to define the metabolic regulation of lysine acetyltransferase (KAT) enzymes. Using a novel chemoproteomic probe, we identify a previously unreported interaction between palmitoyl coenzyme A (palmitoyl-CoA) and KAT enzymes. Further analysis reveals that palmitoyl-CoA is a potent inhibitor of KAT activity and that fatty acyl-CoA precursors reduce cellular histone acetylation levels. These studies implicate fatty acyl-CoAs as endogenous regulators of histone acetylation, and suggest novel strategies for the investigation and metabolic modulation of epigenetic signaling. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Method to produce acetyldiacylglycerols (ac-TAGs) by expression of an acetyltransferase gene isolated from Euonymus alatus (burning bush)

    Energy Technology Data Exchange (ETDEWEB)

    Durrett, Timothy; Ohlrogge, John; Pollard, Michael

    2016-05-03

    The present invention relates to novel diacylglycerol acyltransferase genes and proteins, and methods of their use. In particular, the invention describes genes encoding proteins having diacylglycerol acetyltransferase activity, specifically for transferring an acetyl group to a diacylglycerol substrate to form acetyl-Triacylglycerols (ac-TAGS), for example, a 3-acetyl-1,2-diacyl-sn-glycerol. The present invention encompasses both native and recombinant wild-type forms of the transferase, as well as mutants and variant forms. The present invention also relates to methods of using novel diacylglycerol acyltransferase genes and proteins, including their expression in transgenic organisms at commercially viable levels, for increasing production of 3-acetyl-1,2-diacyl-sn-glycerols in plant oils and altering the composition of oils produced by microorganisms, such as yeast, by increasing ac-TAG production. Additionally, oils produced by methods of the present inventions comprising genes and proteins are contemplated for use as biodiesel fuel, in polymer production and as naturally produced food oils with reduced calories.

  19. An Acetyltransferase Conferring Tolerance to Toxic Aromatic Amine Chemicals

    Science.gov (United States)

    Martins, Marta; Rodrigues-Lima, Fernando; Dairou, Julien; Lamouri, Aazdine; Malagnac, Fabienne; Silar, Philippe; Dupret, Jean-Marie

    2009-01-01

    Aromatic amines (AA) are a major class of environmental pollutants that have been shown to have genotoxic and cytotoxic potentials toward most living organisms. Fungi are able to tolerate a diverse range of chemical compounds including certain AA and have long been used as models to understand general biological processes. Deciphering the mechanisms underlying this tolerance may improve our understanding of the adaptation of organisms to stressful environments and pave the way for novel pharmaceutical and/or biotechnological applications. We have identified and characterized two arylamine N-acetyltransferase (NAT) enzymes (PaNAT1 and PaNAT2) from the model fungus Podospora anserina that acetylate a wide range of AA. Targeted gene disruption experiments revealed that PaNAT2 was required for the growth and survival of the fungus in the presence of toxic AA. Functional studies using the knock-out strains and chemically acetylated AA indicated that tolerance of P. anserina to toxic AA was due to the N-acetylation of these chemicals by PaNAT2. Moreover, we provide proof-of-concept remediation experiments where P. anserina, through its PaNAT2 enzyme, is able to detoxify the highly toxic pesticide residue 3,4-dichloroaniline in experimentally contaminated soil samples. Overall, our data show that a single xenobiotic-metabolizing enzyme can mediate tolerance to a major class of pollutants in a eukaryotic species. These findings expand the understanding of the role of xenobiotic-metabolizing enzyme and in particular of NATs in the adaptation of organisms to their chemical environment and provide a basis for new systems for the bioremediation of contaminated soils. PMID:19416981

  20. Single step synthesis of gold-amino acid composite, with the evidence of the catalytic hydrogen atom transfer (HAT) reaction, for the electrochemical recognition of Serotonin

    Science.gov (United States)

    Choudhary, Meenakshi; Siwal, Samarjeet; Nandi, Debkumar; Mallick, Kaushik

    2016-03-01

    A composite architecture of amino acid and gold nanoparticles has been synthesized using a generic route of 'in-situ polymerization and composite formation (IPCF)' [1,2]. The formation mechanism of the composite has been supported by a model hydrogen atom (H•≡H++e-) transfer (HAT) type of reaction which belongs to the proton coupled electron transfer (PCET) mechanism. The 'gold-amino acid composite' was used as a catalyst for the electrochemical recognition of Serotonin.

  1. Patterns of Direct Projections from the Hippocampus to the Medial Septum-Diagonal Band Complex : Anterograde Tracing with Phaseolus vulgaris Leucoagglutinin Combined with Immunohistochemistry of Choline Acetyltransferase

    NARCIS (Netherlands)

    Gaykema, R.P.A.; Kuil, J. van der; Hersh, L.B.; Luiten, P.G.M.

    1991-01-01

    The projections from the Ammon's horn to the cholinergic cell groups in the medial septal and diagonal band nuclei were investigated with anterograde tracing of Phaseolus vulgaris leucoagglutinin combined with immunocytochemical detection of choline acetyltransferase, in the rat. Tracer injections

  2. GCN5 regulates the activation of PI3K/Akt survival pathway in B cells exposed to oxidative stress via controlling gene expressions of Syk and Btk.

    Science.gov (United States)

    Kikuchi, Hidehiko; Kuribayashi, Futoshi; Takami, Yasunari; Imajoh-Ohmi, Shinobu; Nakayama, Tatsuo

    2011-02-25

    Histone acetyltransferase(s) (HATs) are involved in the acetylation of core histones, which is an important event for transcription regulation through alterations in the chromatin structure in eukaryotes. General control non-depressible 5 (GCN5) was first identified as a global coactivator and transcription-related HAT. Here we report that GCN5 regulates the activation of phosphatidylinositol 3-kinase (PI3K)/acutely transforming retrovirus AKT8 in rodent T cell lymphoma (Akt) survival pathway in B cells exposed to oxidative stress via controlling gene expressions of spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (Btk). The GCN5-deficiency remarkably caused apoptotic cell death by treatment with exogenous hydrogen peroxide (H(2)O(2)) in chicken DT40 cells. In GCN5-deficient DT40 cells, gene expressions of Syk and Btk, which are involved in activation of PI3K/Akt survival pathway in DT40 cells exposed to exogenous H(2)O(2), were remarkably decreased compared with those in wild type DT40 cells. In addition, phosphorylation of Akt in H(2)O(2)-treated GCN5-deficient cells was remarkably suppressed as compared to that of DT40. Chromatin immunoprecipitation assay revealed that GCN5 binds to proximal 5'-upstream regions of Syk and Btk genes in vivo. These results suggest that GCN5 takes part in transcriptional regulations of the Syk and Btk genes, and plays a key role in epigenetic regulation of PI3K/Akt survival pathway in B cells exposed to reactive oxygen species such as H(2)O(2). Copyright © 2011 Elsevier Inc. All rights reserved.

  3. 3D spin-orbit angle of Kepler-25 and HAT-P-7

    Directory of Open Access Journals (Sweden)

    Benomar Othman

    2015-01-01

    Full Text Available The number of discovered exoplanets now exceeds 1500, mostly due to the Kepler space instrument observations. Many of these planet orbit in less than a week around their host stars. This implies that the inward migration of those planets is a basic ingredient of successful theories of planet formation and evolution. Several mechanisms have been proposed to explain the observed periods, which lead to different orbit eccentricity and obliquity distributions. Here we summarise and discuss the results of obliquities for two Kepler stars: HAT-P-7 and Kepler-25. These are interesting stellar systems as we could carry out a joint analysis using asteroseismology, transit lightcurve and the Rossiter-McLaughlin effect in order to measure the three dimensional obliquity.

  4. Recombination analysis based on the complete genome of bocavirus

    Directory of Open Access Journals (Sweden)

    Chen Shengxia

    2011-04-01

    Full Text Available Abstract Bocavirus include bovine parvovirus, minute virus of canine, porcine bocavirus, gorilla bocavirus, and Human bocaviruses 1-4 (HBoVs. Although recent reports showed that recombination happened in bocavirus, no systematical study investigated the recombination of bocavirus. The present study performed the phylogenetic and recombination analysis of bocavirus over the complete genomes available in GenBank. Results confirmed that recombination existed among bocavirus, including the likely inter-genotype recombination between HBoV1 and HBoV4, and intra-genotype recombination among HBoV2 variants. Moreover, it is the first report revealing the recombination that occurred between minute viruses of canine.

  5. Bayesian estimation inherent in a Mexican-hat-type neural network

    Science.gov (United States)

    Takiyama, Ken

    2016-05-01

    Brain functions, such as perception, motor control and learning, and decision making, have been explained based on a Bayesian framework, i.e., to decrease the effects of noise inherent in the human nervous system or external environment, our brain integrates sensory and a priori information in a Bayesian optimal manner. However, it remains unclear how Bayesian computations are implemented in the brain. Herein, I address this issue by analyzing a Mexican-hat-type neural network, which was used as a model of the visual cortex, motor cortex, and prefrontal cortex. I analytically demonstrate that the dynamics of an order parameter in the model corresponds exactly to a variational inference of a linear Gaussian state-space model, a Bayesian estimation, when the strength of recurrent synaptic connectivity is appropriately stronger than that of an external stimulus, a plausible condition in the brain. This exact correspondence can reveal the relationship between the parameters in the Bayesian estimation and those in the neural network, providing insight for understanding brain functions.

  6. Spermidine/spermine N1-acetyltransferase (SSAT) activity in human small-cell lung carcinoma cells following transfection with a genomic SSAT construct.

    Science.gov (United States)

    Murray-Stewart, Tracy; Applegren, Nancy B; Devereux, Wendy; Hacker, Amy; Smith, Renee; Wang, Yanlin; Casero, Robert A

    2003-07-15

    Spermidine/spermine N (1)-acetyltransferase (SSAT) activity is typically highly inducible in non-small-cell lung carcinomas in response to treatment with anti-tumour polyamine analogues, and this induction is associated with subsequent cell death. In contrast, cells of the small-cell lung carcinoma (SCLC) phenotype generally do not respond to these compounds with an increase in SSAT activity, and usually are only moderately affected with respect to growth. The goal of the present study was to produce an SSAT-overexpressing SCLC cell line to further investigate the role of SSAT in response to these anti-tumour analogues. To accomplish this, NCI-H82 SCLC cells were stably transfected with plasmids containing either the SSAT genomic sequence or the corresponding cDNA sequence. Individual clones were selected based on their ability to show induced SSAT activity in response to exposure to a polyamine analogue, and an increase in the steady-state SSAT mRNA level. Cells transfected with the genomic sequence exhibited a significant increase in basal SSAT mRNA expression, as well as enhanced SSAT activity, intracellular polyamine pool depletion and growth inhibition following treatment with the analogue N (1), N (11)-bis(ethyl)norspermine. Cells containing the transfected cDNA also exhibited an increase in the basal SSAT mRNA level, but remained phenotypically similar to vector control cells with respect to their response to analogue exposure. These studies indicate that both the genomic SSAT sequence and polyamine analogue exposure play a role in the transcriptional and post-transcriptional regulation and subsequent induction of SSAT activity in these cells. Furthermore, this is the first production of a cell line capable of SSAT protein induction from a generally unresponsive parent line.

  7. A SEARCH FOR WATER IN THE ATMOSPHERE OF HAT-P-26b USING LDSS-3C

    Energy Technology Data Exchange (ETDEWEB)

    Stevenson, Kevin B.; Bean, Jacob L.; Seifahrt, Andreas; Gilbert, Gregory J. [Department of Astronomy and Astrophysics, University of Chicago, 5640 S Ellis Avenue, Chicago, IL 60637 (United States); Line, Michael R. [NASA Ames Research Center, Moffett Field, CA 94035 (United States); Désert, Jean-Michel [Anton Pannekoek Institute for Astronomy, University of Amsterdam, Amsterdam (Netherlands); Fortney, Jonathan J., E-mail: kbs@uchicago.edu [Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States)

    2016-02-01

    The characterization of a physically diverse set of transiting exoplanets is an important and necessary step toward establishing the physical properties linked to the production of obscuring clouds or hazes. It is those planets with identifiable spectroscopic features that can most effectively enhance our understanding of atmospheric chemistry and metallicity. The newly commissioned LDSS-3C instrument on Magellan provides enhanced sensitivity and suppressed fringing in the red optical, thus advancing the search for the spectroscopic signature of water in exoplanetary atmospheres from the ground. Using data acquired by LDSS-3C and the Spitzer Space Telescope, we search for evidence of water vapor in the transmission spectrum of the Neptune-mass planet HAT-P-26b. Our measured spectrum is best explained by the presence of water vapor, a lack of potassium, and either a high-metallicity, cloud-free atmosphere or a solar-metallicity atmosphere with a cloud deck at ∼10 mbar. The emergence of multi-scale-height spectral features in our data suggests that future observations at higher precision could break this degeneracy and reveal the planet’s atmospheric chemical abundances. We also update HAT-P-26b’s transit ephemeris, t{sub 0} = 2455304.65218(25) BJD{sub TDB}, and orbital period, p = 4.2345023(7) days.

  8. ATMOSPHERE AND SPECTRAL MODELS OF THE KEPLER-FIELD PLANETS HAT-P-7b AND TrES-2

    International Nuclear Information System (INIS)

    Spiegel, David S.; Burrows, Adam

    2010-01-01

    We develop atmosphere models of two of the three Kepler-field planets that were known prior to the start of the Kepler mission (HAT-P-7b and TrES-2). We find that published Kepler and Spitzer data for HAT-P-7b appear to require an extremely hot upper atmosphere on the dayside, with a strong thermal inversion and little day-night redistribution. The Spitzer data for TrES-2 suggest a mild thermal inversion with moderate day-night redistribution. We examine the effect of nonequilibrium chemistry on TrES-2 model atmospheres and find that methane levels must be adjusted by extreme amounts in order to cause even mild changes in atmospheric structure and emergent spectra. Our best-fit models to the Spitzer data for TrES-2 lead us to predict a low secondary eclipse planet-star flux ratio (∼ -5 ) in the Kepler bandpass, which is consistent with what very recent observations have found. Finally, we consider how the Kepler-band optical flux from a hot exoplanet depends on the strength of a possible extra optical absorber in the upper atmosphere. We find that the optical flux is not monotonic in optical opacity, and the non-monotonicity is greater for brighter, hotter stars.

  9. Oxygenation measurements in head and neck cancers during hyperbaric oxygenation

    International Nuclear Information System (INIS)

    Becker, A.; Kuhnt, T.; Dunst, J.; Liedtke, H.; Krivokuca, A.; Bloching, M.

    2002-01-01

    Background: Tumor hypoxia has proven prognostic impact in head and neck cancers and is associated with poor response to radiotherapy. Hyperbaric oxygenation (HBO) offers an approach to overcome hypoxia. We have performed pO 2 measurements in selected patients with head and neck cancers under HBO to determine in how far changes in the oxygenation occur and whether a possible improvement of oxygenation parameters is maintained after HBO. Patients and Methods: Seven patients (five male, two female, age 51-63 years) with squamous cell cancers of the head and neck were investigated (six primaries, one local recurrence). The median pO 2 prior to HBO was determined with the Eppendorf histograph. Sites of measurement were enlarged cervical lymph nodes (n = 5), the primary tumor (n = 1) and local recurrence (n = 1). Patients then underwent HBO (100% O 2 at 240 kPa for 30 minutes) and the continuous changes in the oxygenation during HBO were determined with a Licox probe. Patients had HBO for 30 minutes (n = 6) to 40 minutes (n = 1). HBO was continued because the pO 2 had not reached a steady state after 30 minutes. After decompression, patients ventilated pure oxygen under normobaric conditions and the course of the pO 2 was further measured over about 15 minutes. Results: Prior to HBO, the median tumor pO 2 in the Eppendorf histography was 8.6 ± 5.4 mm Hg (range 3-19 mm Hg) and the pO 2 measured with the Licox probe was 17.3 ± 25.5 mm Hg (range 0-73 mm Hg). The pO 2 increased significantly during HBO to 550 ± 333 mm Hg (range 85-984 mm Hg, p = 0.018). All patients showed a marked increase irrespective of the oxygenation prior to HBO. The maximum pO 2 in the tumor was reached after 10-33 minutes (mean 17 minutes). After leaving the hyperbaric chamber, the pO 2 was 282 ± 196 mm Hg. All patients maintained an elevated pO 2 for further 5-25 minutes (138 ± 128 mm Hg, range 42-334 mm Hg, p = 0.028 vs the pO 2 prior to HBO). Conclusions: Hyperbaric oxygenation resulted in a

  10. Functional Characterization of ATM Kinase Using Acetylation-Specific Antibodies.

    Science.gov (United States)

    Sun, Yingli; Du, Fengxia

    2017-01-01

    The activation of ATM is critical in the DNA double strand breaks repair pathway. Acetylation of ATM by Tip60 histone acetyltransferase (HAT) plays a key role in the activation of ATM kinase activity in response to DNA damage. ATM forms a stable complex with Tip60 through the FATC domain of ATM. Tip60 acetylates lysine3016 of ATM, and this acetylation induces the activation of ATM. Several techniques are included in the study of ATM acetylation by Tip60, such as in vitro kinase assay, systematic mutagenesis, western blots. Here, we describe how to study the acetylation of ATM using acetylation-specific antibodies.

  11. Characterization of the serine acetyltransferase gene family of Vitis vinifera uncovers differences in regulation of OAS synthesis in woody plants

    OpenAIRE

    Silvia eTavares; Silvia eTavares; Markus eWirtz; Marcel Pascal Beier; Jochen eBogs; Jochen eBogs; Jochen eBogs; Ruediger eHell; Sara eAmâncio

    2015-01-01

    In higher plants cysteine biosynthesis is catalyzed by O-acetylserine(thiol)lyase (OASTL) and represents the last step of the assimilatory sulfate reduction pathway. It is mainly regulated by provision of O-acetylserine (OAS), the nitrogen/carbon containing backbone for fixation of reduced sulfur. OAS is synthesized by Serine acetyltransferase (SERAT), which reversibly interacts with OASTL in the cysteine synthase complex (CSC). In this study we identify and characterize the SERAT protein fam...

  12. Characterization of the serine acetyltransferase gene family of Vitis vinifera uncovers differences in regulation of OAS synthesis in woody plants

    OpenAIRE

    Tavares, Sílvia; Wirtz, Markus; Beier, Marcel P.; Bogs, Jochen; Hell, Rüdiger; Amâncio, Sara

    2015-01-01

    In higher plants cysteine biosynthesis is catalyzed by O-acetylserine(thiol)lyase (OASTL) and represents the last step of the assimilatory sulfate reduction pathway. It is mainly regulated by provision of O-acetylserine (OAS), the nitrogen/carbon containing backbone for fixation of reduced sulfur. OAS is synthesized by Serine acetyltransferase (SERAT), which reversibly interacts with OASTL in the cysteine synthase complex (CSC). In this study we identify and characterize the SERAT gene family...

  13. Kepler and Ground-Based Transits of the exo-Neptune HAT-P-11b

    Science.gov (United States)

    Deming, Drake; Sada, Pedro V.; Jackson, Brian; Peterson, Steven W.; Agol, Eric; Knutson, Heather A.; Jennings, Donald E.; Haase, Plynn; Bays, Kevin

    2011-01-01

    We analyze 26 archival Kepler transits of the exo-Neptune HAT-P-11b, supplemented by ground-based transits observed in the blue (B band) and near-IR (J band). Both the planet and host star are smaller than previously believed; our analysis yields Rp = 4.31 R xor 0.06 R xor and Rs = 0.683 R solar mass 0.009 R solar mass, both about 3 sigma smaller than the discovery values. Our ground-based transit data at wavelengths bracketing the Kepler bandpass serve to check the wavelength dependence of stellar limb darkening, and the J-band transit provides a precise and independent constraint on the transit duration. Both the limb darkening and transit duration from our ground-based data are consistent with the new Kepler values for the system parameters. Our smaller radius for the planet implies that its gaseous envelope can be less extensive than previously believed, being very similar to the H-He envelope of GJ 436b and Kepler-4b. HAT-P-11 is an active star, and signatures of star spot crossings are ubiquitous in the Kepler transit data. We develop and apply a methodology to correct the planetary radius for the presence of both crossed and uncrossed star spots. Star spot crossings are concentrated at phases 0.002 and +0.006. This is consistent with inferences from Rossiter-McLaughlin measurements that the planet transits nearly perpendicular to the stellar equator. We identify the dominant phases of star spot crossings with active latitudes on the star, and infer that the stellar rotational pole is inclined at about 12 deg 5 deg to the plane of the sky. We point out that precise transit measurements over long durations could in principle allow us to construct a stellar Butterfly diagram to probe the cyclic evolution of magnetic activity on this active K-dwarf star.

  14. Effect of hyperbaric oxygenation on mitochondrial function of neuronal cells in the cortex of neonatal rats after hypoxic-ischemic brain damage

    Directory of Open Access Journals (Sweden)

    L. Yang

    2016-01-01

    Full Text Available The timing and mechanisms of protection by hyperbaric oxygenation (HBO in hypoxic-ischemic brain damage (HIBD have only been partially elucidated. We monitored the effect of HBO on the mitochondrial function of neuronal cells in the cerebral cortex of neonatal rats after HIBD. Neonatal Sprague-Dawley rats (total of 360 of both genders were randomly divided into normal control, HIBD, and HIBD+HBO groups. The HBO treatment began immediately after hypoxia-ischemia (HI and continued once a day for 7 consecutive days. Animals were euthanized 0, 2, 4, 6, and 12 h post-HI to monitor the changes in mitochondrial membrane potential (ΔΨm occurring soon after a single dose of HBO treatment, as well as 2, 3, 4, 5, 6, and 7 days post-HI to study ΔΨm changes after a series of HBO treatments. Fluctuations in ΔΨm were observed in the ipsilateral cortex in both HIBD and HIBD+HBO groups. Within 2 to 12 h after HI insult, the ΔΨm of the HIBD and HIBD+HBO groups recovered to some extent. A secondary drop in ΔΨm was observed in both groups during the 1-4 days post-HI period, but was more severe in the HIBD+HBO group. There was a secondary recovery of ΔΨm observed in the HIBD+HBO group, but not in the HIBD group, during the 5-7 days period after HI insult. HBO therapy may not lead to improvement of neural cell mitochondrial function in the cerebral cortex in the early stage post-HI, but may improve it in the sub-acute stage post-HI.

  15. Benzodiazepines: rat pinealocyte binding sites and augmentation of norepinephrine-stimulated N-acetyltransferase activity

    Energy Technology Data Exchange (ETDEWEB)

    Matthew, E.; Parfitt, A.G.; Sugden, D.; Engelhardt, D.L.; Zimmerman, E.A.; Klein, D.C.

    1984-02-01

    Studies of (/sup 3/H)diazepam binding to intact rat pineal cells were carried out in tissue culture preparations. The binding was saturable, reversible and proportional to the number of cells used. Scatchard analysis resulted in a linear plot (Kd . 23 nM, maximum binding sites (Bmax) . 1.56 pmol/mg of protein for cells in monolayer culture; Kd . 7 nM, Bmax . 1.3 pmol/mg of protein for cells in suspension culture). Inhibition constants (Ki) for clonazepam (500 nM), flunitrazepam (38 nM) and Ro-5-4864 (5 nM) indicated that the binding sites were probably of the ''peripheral'' type. In addition, the effects of diazepam on norepinephrine-stimulated N-acetyltransferase (NAT) activity were studied in organ culture and dissociated cell culture. Diazepam (10-50 microM) both prolonged and increased the magnitude of the norepinephrine-induced increase in NAT activity but did not affect the initial rate of rise of enzyme activity. The effect was dose-dependent and was also seen with clonazepam, flunitrazepam and Ro-5-4864, but not with Ro-15-1788. Diazepam, by itself, at these concentrations, had no effect on NAT, but enzyme activity was increased by higher concentrations (0.1-1 mM). Although a relationship between the (/sup 3/H)diazepam binding sites described here and the effect of benzodiazepines on NAT cannot be established from these studies, the data suggest that the benzodiazepines may alter melatonin levels through their action on NAT.

  16. Ein Nachkömmling Tristans : Warum hat Theodor Storm in seiner Novelle „Späte Rosen" Gottfried von Straßburgs „Tristan und Isolde" erwähnt?

    OpenAIRE

    田淵, 昌太

    2010-01-01

    Man hat bisher Theodor Storms Novelle „Späte Rosen" für ein Werk gehalten, das ein friedliches Familienleben beziehungweise das tägliche Zusammenleben eines Ehepaars schildert. Zum Beispiel hat Beate Charlotte Göhler in ihrer umfangreichen Storm-Biografie geschrieben, dass Theodor Storm mit diesem Werk seiner Frau Constanze eine Liebeserklärung machte („Ein Leben für die Graue Stadt" S.198). Wenn man diese Novelle nur oberflächlich liest, ist es eine mögliche Folge, dass man „Späte Rosen"...

  17. Nipple Reduction With the Chullo-Hat Technique.

    Science.gov (United States)

    Sim, Hyung-Bo; Sun, Sang-Hoon

    2015-08-01

    Although various techniques of nipple reduction have been described in the literature, many are difficult to design or have unreliable outcomes. For men, as well as women who do not plan to breastfeed, it is not necessary to apply a complicated technique that protects the lactiferous ducts. The authors introduce a simple technique for nipple reduction that has achieved consistent, reproducible results. The desired nipple length is marked, and a chullo-hat excision pattern is drawn. After infiltration of a local anesthetic solution around the nipple, excision of the excess nipple tissue is performed, comprising 2 triangular flaps. The remaining 2 pillars are approximated with 5-0 Nylon simple interrupted sutures. However, the wound is not completely closed in the central area of the nipple, which promotes the drainage of discharge. Fifty-three women (106 nipples) underwent this surgery between December 2009 and December 2013. The follow-up period ranged from 6 months to 2 years (mean, 10 months). No major complications occurred, and the scars were very inconspicuous. The postoperative appearance of nipples was consistently similar in size and shape. This simple technique was safe and effective in nipples of different sizes. The results were reliable and consistent with expectations. Although this study included only women, the authors believe that outcomes would be successful in men as well. 4 Therapeutic. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

  18. Hyperbaric oxygen preconditioning protects against traumatic brain injury at high altitude.

    Science.gov (United States)

    Hu, S L; Hu, R; Li, F; Liu, Z; Xia, Y Z; Cui, G Y; Feng, H

    2008-01-01

    Recent studies have shown that preconditioning with hyperbaric oxygen (HBO) can reduce ischemic and hemorrhagic brain injury. We investigated effects of HBO preconditioning on traumatic brain injury (TBI) at high altitude and examined the role of matrix metalloproteinase-9 (MMP-9) in such protection. Rats were randomly divided into 3 groups: HBO preconditioning group (HBOP; n = 13), high-altitude group (HA; n = 13), and high-altitude sham operation group (HASO; n = 13). All groups were subjected to head trauma by weight-drop device, except for HASO group. HBOP rats received 5 sessions of HBO preconditioning (2.5 ATA, 100% oxygen, 1 h daily) and then were kept in hypobaric chamber at 0.6 ATA (to simulate pressure at 4000m altitude) for 3 days before operation. HA rats received control pretreatment (1 ATA, room air, 1 h daily), then followed the same procedures as HBOP group. HASO rats were subjected to skull opening only without brain injury. Twenty-four hours after TBI, 7 rats from each group were examined for neurological function and brain water content; 6 rats from each group were killed for analysis by H&E staining and immunohistochemistry. Neurological outcome in HBOP group (0.71 +/- 0.49) was better than HA group (1.57 +/- 0.53; p < 0.05). Preconditioning with HBO significantly reduced percentage of brain water content (86.24 +/- 0.52 vs. 84.60 +/- 0.37; p < 0.01). Brain morphology and structure seen by light microscopy was diminished in HA group, while fewer pathological injuries occurred in HBOP group. Compared to HA group, pretreatment with HBO significantly reduced the number of MMP-9-positive cells (92.25 +/- 8.85 vs. 74.42 +/- 6.27; p < 0.01). HBO preconditioning attenuates TBI in rats at high altitude. Decline in MMP-9 expression may contribute to HBO preconditioning-induced protection of brain tissue against TBI.

  19. Hyperbaric oxygen therapy for cognitive disorders after irradiation of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Hulshof, M C.C.M.; Sminia, P; Gonzalez, D G [Amsterdam Univ. (Netherlands). Dept. of Radiation Oncology; Stark, N M; Smeding, H M.M. [Amsterdam Univ. (Netherlands). Dept. of Neurology; Kleij, A van der [Amsterdam Univ. (Netherlands). Dept. of Surgery/Hyperbaric Oxygen

    2002-04-01

    Purpose: Analysis of the feasibility and effect of hyperbaric oxygen treatment (HBO) on cognitive functioning in patients with cognitive disorders after irradiation of the brain. Patients and Method: Seven patients with cognitive impairment after brain irradiation, with an interval of at least 1.5 years after treatment, were treated with 30 sessions of HBO in a phase I-II study. A comprehensive neuropsychological test battery was performed before treatment, at 3 and 6 months thereafter. Patients were randomized into an immediate treatment group and a delayed treatment group. The delayed group had a second neurospychological test at 3 months without treatment in that period and started HBO thereafter. Results: All eligible patients completed the HBO treatment and the extensive neuropsychological testing. One out of seven patients had a meaningful improvement in neuropsychological functioning. At 3 months there was a small, but not significant benefit in neuropsychological performance for the group with HBO compared to the group without HBO treatment. Six out of seven patients eventually showed improvement after HBO in one to nine (median 2.5) of the 31 tests, although without statistical significance. Conclusion: HBO treatment was feasible and resulted in a meaningful improvement of cognitive functioning in one out of seven patients. Overall there was a small but not significant improvement. (orig.)

  20. Hyperbaric oxygen therapy for cognitive disorders after irradiation of the brain

    International Nuclear Information System (INIS)

    Hulshof, M.C.C.M.; Sminia, P.; Gonzalez, D.G.; Stark, N.M.; Smeding, H.M.M.; Kleij, A. van der

    2002-01-01

    Purpose: Analysis of the feasibility and effect of hyperbaric oxygen treatment (HBO) on cognitive functioning in patients with cognitive disorders after irradiation of the brain. Patients and Method: Seven patients with cognitive impairment after brain irradiation, with an interval of at least 1.5 years after treatment, were treated with 30 sessions of HBO in a phase I-II study. A comprehensive neuropsychological test battery was performed before treatment, at 3 and 6 months thereafter. Patients were randomized into an immediate treatment group and a delayed treatment group. The delayed group had a second neurospychological test at 3 months without treatment in that period and started HBO thereafter. Results: All eligible patients completed the HBO treatment and the extensive neuropsychological testing. One out of seven patients had a meaningful improvement in neuropsychological functioning. At 3 months there was a small, but not significant benefit in neuropsychological performance for the group with HBO compared to the group without HBO treatment. Six out of seven patients eventually showed improvement after HBO in one to nine (median 2.5) of the 31 tests, although without statistical significance. Conclusion: HBO treatment was feasible and resulted in a meaningful improvement of cognitive functioning in one out of seven patients. Overall there was a small but not significant improvement. (orig.)

  1. Attenuating brain edema, hippocampal oxidative stress, and cognitive dysfunction in rats using hyperbaric oxygen preconditioning during simulated high-altitude exposure.

    Science.gov (United States)

    Lin, Hung; Chang, Ching-Ping; Lin, Hung-Jung; Lin, Mao-Tsun; Tsai, Cheng-Chia

    2012-05-01

    We assessed whether hyperbaric oxygen preconditioning (HBO2P) in rats induced heat shock protein (HSP)-70 and whether HSP-70 antibody (Ab) preconditioning attenuates high altitude exposure (HAE)-induced brain edema, hippocampal oxidative stress, and cognitive dysfunction. Rats were randomly divided into five groups: the non-HBO2P + non-HAE group, the HBO2P + non-HAE group, the non-HBO2P + HAE group, the HBO2P + HAE group, and the HBO2P + HSP-70 Abs + HAE group. The HBO2P groups were given 100% O2 at 2.0 absolute atmospheres for 1 hour per day for 5 consecutive days. The HAE groups were exposed to simulated HAE (9.7% O2 at 0.47 absolute atmospheres of 6,000 m) in a hypobaric chamber for 3 days. Polyclonal rabbit anti-mouse HSP-70-neutralizing Abs were intravenously injected 24 hours before the HAE experiments. Immediately after returning to normal atmosphere, the rats were given cognitive performance tests, overdosed with a general anesthetic, and then their brains were excised en bloc for water content measurements and biochemical evaluation and analysis. Non-HBO2P group rats displayed cognitive deficits, brain edema, and hippocampal oxidative stress (evidenced by increased toxic oxidizing radicals [e.g., nitric oxide metabolites and hydroxyl radicals], increased pro-oxidant enzymes [e.g., malondialdehyde and oxidized glutathione] but decreased antioxidant enzymes [e.g., reduced glutathione, glutathione peroxide, glutathione reductase, and superoxide dismutase]) in HAE. HBO2P induced HSP-70 overexpression in the hippocampus and significantly attenuated HAE-induced brain edema, cognitive deficits, and hippocampal oxidative stress. The beneficial effects of HBO2P were significantly reduced by HSP-70 Ab preconditioning. Our results suggest that high-altitude cerebral edema, cognitive deficit, and hippocampal oxidative stress can be prevented by HSP-70-mediated HBO2P in rats.

  2. The Occupancy Rate Modeling of Kendari Hotel Room using Mexican Hat Transformation and Partial Least Squares

    Directory of Open Access Journals (Sweden)

    Margaretha Ohyver

    2016-12-01

    Full Text Available Partial Least Squares (PLS method was developed in 1960 by Herman Wold. The method particularly suits with construct a regression model when the number of independent variables is many and highly collinear. The PLS can be combined with other methods, one of which is a Continuous Wavelet Transformation (CWT. By considering that the presence of outliers can lead to a less reliable model, and this kind of transformation may be required at a stage of pre-processing, the data is free of noise or outliers. Based on the previous study, Kendari hotel room occupancy rate was affected by the outlier, and it had a low value of R2. Therefore, this research aimed to obtain a good model by combining the PLS method and CWT transformation using the Mexican Hats them other wavelet of CWT. The research concludes that merging the PLS and the Mexican Hat transformation has resulted in a better model compared to the model that combined the PLS and the Haar wavelet transformation as shown in the previous study. The research shows that by changing the mother of the wavelet, the value of R2 can be improved significantly. The result provides information on how to increase the value of R2. The other advantage is the information for hotel managements to notice the age of the hotel, the maximum rates, the facilities, and the number of rooms to increase the number of visitors.

  3. Climatic change and environmental implications in the Medicine Hat region using Billings, Montana as an analogue

    International Nuclear Information System (INIS)

    Proudfoot, W.A.

    1994-01-01

    There is concern that climatic change due to anthropogenic enhancement of the greenhouse effect may have considerable impacts on the natural and agricultural environments in Canada. The Palliser Triangle in the southern prairie region is an area in which the impacts of climatic change could be significant; it is an important agricultural zone and is already sensitive due to its semi-arid climate. The possible effects of a change in the climate of the Medicine Hat (Alberta) area in the Palliser Triangle is examined through the use of a regional analogue in a warmer, more southerly area. The selected analogue region is the area around Billings, Montana. Aspects of the natural environment, including potential vegetation distribution, frost-free period, and drought, as well as aspects of the agricultural environment, including agricultural practices and examination of wheat yields, are studied within each region. Comparisons are drawn between the two regions to evaluate whether significant differences exist in the environmental aspects examined. It is shown that although a change in Medicine Hat's climate to one more like that of Billings may not have drastic impacts on the environment, such a change may require adjustments in current practices or adaptations to altered environmental conditions. Reviews of several policy areas will be necessary to ensure appropriate adjustments in agricultural or resource management practices. Regional analogy is shown to be an essential preliminary tool for determining possible effects of climatic change. 138 refs., 42 figs., 22 tabs

  4. Identification of critical residues of the serotype modifying O-acetyltransferase of Shigella flexneri

    Directory of Open Access Journals (Sweden)

    Thanweer Farzaana

    2012-07-01

    Full Text Available Abstract Background Thirteen serotypes of Shigella flexneri (S. flexneri have been recognised, all of which are capable of causing bacillary dysentery or shigellosis. With the emergence of the newer S. flexneri serotypes, the development of an effective vaccine has only become more challenging. One of the factors responsible for the generation of serotype diversity is an LPS O-antigen modifying, integral membrane protein known as O-acetyltransferase or Oac. Oac functions by adding an acetyl group to a specific O-antigen sugar, thus changing the antigenic signature of the parent S. flexneri strain. Oac is a membrane protein, consisting of hydrophobic and hydrophilic components. Oac bears homology to several known and predicted acetyltransferases with most homology existing in the N-terminal transmembrane (TM regions. Results In this study, the conserved motifs in the TM regions and in hydrophilic loops of S. flexneri Oac were targeted for mutagenesis with the aim of identifying the amino acid residues essential for the function of Oac. We previously identified three critical arginines–R73, R75 and R76 in the cytoplasmic loop 3 of Oac. Re-establishing that these arginines are critical, in this study we suggest a catalytic role for R73 and a structural role for R75 and R76 in O-acetylation. Serine-glycine motifs (SG 52–53, GS 138–139 and SYG 274–276, phenylalanine-proline motifs (FP 78–79 and FPV 282–84 and a tryptophan-threonine motif (WT141-142 found in TM segments and residues RK 110–111, GR 269–270 and D333 found in hydrophilic loops were also found to be critical to Oac function. Conclusions By studying the effect of the mutations on Oac’s function and assembly, an insight into the possible roles played by the chosen amino acids in Oac was gained. The transmembrane serine-glycine motifs and hydrophilic residues (RK 110–111, GR 269–270 and D333 were shown to have an affect on Oac assembly which suggests a structural role

  5. Association of N-acetyltransferase-2 and glutathione S-transferase polymorphisms with idiopathic male infertility in Vietnam male subjects.

    Science.gov (United States)

    Trang, Nguyen Thi; Huyen, Vu Thi; Tuan, Nguyen Thanh; Phan, Tran Duc

    2018-04-25

    N-acetyltransferase-2 (NAT2) and Glutathione S-transferases (GSTs) are phase-II xenobiotic metabolizing enzymes participating in detoxification of toxic arylamines, aromatic amines, hydrazines and reactive oxygen species (ROS), which are produced under oxidative and electrophile stresses. The purpose of this research was to investigate whether two common single-nucleotide polymorphisms (SNP) of NAT2 (rs1799929, rs1799930) and GSTP1 (rs1138272, rs1695) associated with susceptibility to idiopathic male infertility. A total 300 DNA samples (150 infertile patients and 150 healthy control) were genotyped for the polymorphisms by ARMS - PCR. We revealed a significant association between the NAT2 variant genotypes (CT + TT (rs1799929), (OR: 3.74; p male infertility in subjects from Vietnam. This pilot study is the first (as far as we know) to reveal that polymorphisms of NAT2 (rs1799929, rs1799930) and GSTP1 (rs1138272, rs1695) are some novel genetic markers for susceptibility to idiopathic male infertility. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. A near-infrared transmission spectrum for the warm Saturn HAT-P-12b

    Energy Technology Data Exchange (ETDEWEB)

    Line, Michael R.; Knutson, Heather; Desert, Jean-Michel [Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125 (United States); Deming, Drake; Wilkins, Ashlee, E-mail: mrl@gps.caltech.edu [Department of Astronomy, University of Maryland, College Park, MD 20742 (United States)

    2013-12-01

    We present a Hubble Space Telescope Wide Field Camera-3 (WFC3) transmission spectrum for the transiting exoplanet HAT-P-12b. This warm (1000 K) sub-Saturn-mass planet has a smaller mass and a lower temperature than the hot Jupiters that have been studied so far. We find that the planet's measured transmission spectrum lacks the expected water absorption feature for a hydrogen-dominated atmosphere and is instead best described by a model with high-altitude clouds. Using a frequentist hypothesis testing procedure, we can rule out a hydrogen-dominated cloud-free atmosphere to 4.9σ. When combined with other recent WFC3 studies, our observations suggest that clouds may be common in exoplanetary atmospheres.

  7. Expression of T helper cell-associated inflammatory mediator mRNAs in cells of bronchoalveolar lavage fluid samples and oxygen concentration in arterial blood samples from healthy horses exposed to hyperbaric oxygen.

    Science.gov (United States)

    Looijen, Maty G P; New, Dallas J; Fischer, Carrie D; Dardari, Rkia; Irwin, Karyn M; Berezowski, Christopher J; Bond, Stephanie L; Léguillette, Renaud

    2016-10-01

    OBJECTIVE To evaluate the mRNA expression of T helper (Th)1, Th2, and Th17 cell-associated inflammatory mediators in cells of bronchoalveolar lavage fluid samples collected from healthy horses exposed to hyperbaric oxygen (HBO) and to monitor blood oxygen concentration during and following HBO therapy. ANIMALS 8 healthy horses. PROCEDURES In a randomized controlled crossover design study, each horse was exposed (beginning day 1) to 100% oxygen at a maximum of 3 atmospheres absolute (304 kPa) daily for 10 days or ambient air at atmospheric pressure in the HBO chamber for an equivalent amount of time (control). Bronchoalveolar lavage fluid samples were collected on days 0 and 10. After validation of candidate reference genes, relative mRNA expressions of various innate inflammatory, Th1 cell-derived, Th2 cell-derived (including eotaxin-2), Th17 cell-derived, and regulatory cytokines were measured by quantitative PCR assays. For 3 horses, arterial blood samples were collected for blood gas analysis during a separate HBO session. RESULTS The optimal combination of reference genes was glyceraldehyde-3-phosphate dehydrogenase, hypoxanthine ribosyltransferase, and ribosomal protein L32. Compared with day 0 findings, expression of eotaxin-2 mRNA was significantly lower (0.12-fold reduction) and the percentage of neutrophils in bronchoalveolar lavage fluid samples was significantly lower on day 10 when horses received HBO therapy. Values of Pao2 rapidly increased (> 800 mm Hg) but immediately decreased to pretreatment values when HBO sessions ended. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that HBO therapy does not increase mRNA expression of inflammatory cytokines, but reduces eotaxin-2 mRNA transcription. The Pao2 increase was transient with no cumulative effects of HBO.

  8. Signaling pathways involved in HSP32 induction by hyperbaric oxygen in rat spinal neurons

    Directory of Open Access Journals (Sweden)

    Guoyang Huang

    2016-12-01

    Full Text Available Spinal cord injury (SCI is a debilitating disease, effective prevention measures are in desperate need. Our previous work found that hyperbaric oxygen (HBO preconditioning significantly protected rats from SCI after stimulated diving, and in vitro study further testified that HBO protected primary cultured rat spinal neurons from oxidative insult and oxygen glucose deprivation injury via heat shock protein (HSP 32 induction. In this study, underlying molecular mechanisms were further investigated. The results showed that a single exposure to HBO significantly increased intracellular levels of reactive oxygen species (ROS and nitric oxide (NO and activated MEK1/2, ERK1/2, p38 MAPK, CREB, Bach1 and Nrf2. The induction of HSP32 by HBO was significantly reversed by pretreatment neurons with ROS scavenger N-Acetyl-L-cysteine, p38 MAPK inhibitor or Nrf2 gene knockdown, enhanced by MEK1/2 inhibitors or gene knockdown but not by ERK1/2 inhibitor. CREB knockdown did not change the expression of HSP32 induced by HBO. N-Acetyl-L-cysteine significantly inhibited the activation of MEK1/2, ERK1/2, p38 MAPK, and Nrf2. Activation of Nrf2 was significantly inhibited by p38 MAPK inhibitor and the nuclear export of Bach1 was significantly enhanced by MEK1/2 inhibitor. The results demonstrated that HBO induces HSP32 expression through a ROS/p38 MAPK/Nrf2 pathway and the MEK1/2/Bach1 pathway contributes to negative regulation in the process. More importantly, as we know, this is the first study to delineate that ERK1/2 is not the only physiological substrates of MEK1/2.

  9. Engineering assessment of inactive uranium mill tailings, Mexican Hat site, Mexican Hat, Utah. A summary of the Phase II, Title I

    International Nuclear Information System (INIS)

    1977-01-01

    Ford, Bacon and Davis Utah Inc. has performed an engineering assessment of the problems resulting from the existence of radioactive uranium mill tailings at the Mexican Hat millsite in Utah. The Phase II, Title I services include the preparation of topographic maps, the performance of core drillings and radiometric measurements sufficient to determine areas and volumes of tailings and other radium-contaminated materials, the evaluation of resulting radiation exposures of individuals residing nearby, the investigation of site hydrology and meteorology, and the evaluation and costing of alternative corrective actions. Radon gas release from the 2,200,000 tons of tailings on the site constitutes the most significant environmental impact. The six alternative actions presented are directed towards restricting access to the site (Option I), returning the windblown tailings to the piles and stabilizing the piles with cover material (Options II, III, and IV), and consolidating the two piles into one pile and stabilizing it with cover material (Options V and VI). Fencing around the site or the tailings and the decontamination of mill buildings is included in all options. Options II and V provide 2 ft of cover material on the tailings, Options III, IV, and VI provide 4 ft, 13 ft, and 10 ft of cover, respectively. Costs of the options range from $370,000 to $4,390,000. Reprocessing the tailings for uranium is not feasible at present

  10. Hyperbaric oxygen and radiotherapy

    International Nuclear Information System (INIS)

    Mayer, R.; Hamilton-Farrell, M.R.; Kleij, A.J. van der

    2005-01-01

    Background: Hyperbaric oxygen (HBO) therapy is the inhalation of 100% oxygen at a pressure of at least 1.5 atmospheres absolute (150 kPa). It uses oxygen as a drug by dissolving it in the plasma and delivering it to the tissues independent of hemoglobin. For a variety of organ systems, HBO is known to promote new vessel growth into areas with reduced oxygen tension due to poor vascularity, and therewith promotes wound healing and recovery of radiation-injured tissue. Furthermore, tumors may be sensitized to irradiation by raising intratumoral oxygen tensions. Methods: A network of hyperbaric facilities exists in Europe, and a number of clinical studies are ongoing. The intergovernmental framework COST B14 action 'Hyperbaric Oxygen Therapy' started in 1999. The main goal of the Working Group Oncology is preparation and actual implementation of prospective study protocols in the field of HBO and radiation oncology in Europe. Results: In this paper a short overview on HBO is given and the following randomized clinical studies are presented: (a) reirradiation of recurrent squamous cell carcinoma of the head and neck after HBO sensitization; (b) role of HBO in enhancing radiosensitivity on glioblastoma multiforme; (c) osseointegration in irradiated patients; adjunctive HBO to prevent implant failures; (d) the role of HBO in the treatment of late irradiation sequelae in the pelvic region. The two radiosensitization protocols (a, b) allow a time interval between HBO and subsequent irradiation of 10-20 min. Conclusion: Recruitment of centers and patients is being strongly encouraged, detailed information is given on www.oxynet.org. (orig.)

  11. The small delta antigen of hepatitis delta virus is an acetylated protein and acetylation of lysine 72 may influence its cellular localization and viral RNA synthesis

    International Nuclear Information System (INIS)

    Mu, J.-J.; Tsay, Y.-G.; Juan, L.-J.; Fu, T.-F.; Huang, W.-H.; Chen, D.-S.; Chen, P.-J.

    2004-01-01

    Hepatitis delta virus (HDV) is a single-stranded RNA virus that encodes two viral nucleocapsid proteins named small and large form hepatitis delta antigen (S-HDAg and L-HDAg). The S-HDAg is essential for viral RNA replication while the L-HDAg is required for viral assembly. In this study, we demonstrated that HDAg are acetylated proteins. Metabolic labeling with [ 3 H]acetate revealed that both forms of HDAg could be acetylated in vivo. The histone acetyltransferase (HAT) domain of cellular acetyltransferase p300 could acetylate the full-length and the N-terminal 88 amino acids of S-HDAg in vitro. By mass spectrometric analysis of the modified protein, Lys-72 of S-HDAg was identified as one of the acetylation sites. Substitution of Lys-72 to Arg caused the mutant S-HDAg to redistribute from the nucleus to the cytoplasm. The mutant reduced viral RNA accumulation and resulted in the earlier appearance of L-HDAg. These results demonstrated that HDAg is an acetylated protein and mutation of HDAg at Lys-72 modulates HDAg subcellular localization and may participate in viral RNA nucleocytoplasmic shuttling and replication

  12. Hippocampal Focal Knockout of CBP Affects Specific Histone Modifications, Long-Term Potentiation, and Long-Term Memory

    Science.gov (United States)

    Barrett, Ruth M; Malvaez, Melissa; Kramar, Eniko; Matheos, Dina P; Arrizon, Abraham; Cabrera, Sara M; Lynch, Gary; Greene, Robert W; Wood, Marcelo A

    2011-01-01

    To identify the role of the histone acetyltransferase (HAT) CREB-binding protein (CBP) in neurons of the CA1 region of the hippocampus during memory formation, we examine the effects of a focal homozygous knockout of CBP on histone modifications, gene expression, synaptic plasticity, and long-term memory. We show that CBP is critical for the in vivo acetylation of lysines on histones H2B, H3, and H4. CBP's homolog p300 was unable to compensate for the loss of CBP. Neurons lacking CBP maintained phosphorylation of the transcription factor CREB, yet failed to activate CREB:CBP-mediated gene expression. Loss of CBP in dorsal CA1 of the hippocampus resulted in selective impairments to long-term potentiation and long-term memory for contextual fear and object recognition. Together, these results suggest a necessary role for specific chromatin modifications, selectively mediated by CBP in the consolidation of memories. PMID:21508930

  13. 5-methyl-tetrahydrofolate and the S-adenosylmethionine cycle in C57BL/6J mouse tissues: gender differences and effects of arylamine N-acetyltransferase-1 deletion.

    Directory of Open Access Journals (Sweden)

    Katey L Witham

    Full Text Available Folate catabolism involves cleavage of the C(9-N(10 bond to form p-aminobenzoylgluamate (PABG and pterin. PABG is then acetylated by human arylamine N-acetyltransferase 1 (NAT1 before excretion in the urine. Mice null for the murine NAT1 homolog (Nat2 show several phenotypes consistent with altered folate homeostasis. However, the exact role of Nat2 in the folate pathway in vivo has not been reported. Here, we examined the effects of Nat2 deletion in male and female mice on the tissue levels of 5-methyl-tetrahydrofolate and the methionine-S-adenosylmethionine cycle. We found significant gender differences in hepatic and renal homocysteine, S-adenosylmethionine and methionine levels consistent with a more active methionine-S-adenosylmethionine cycle in female tissues. In addition, methionine levels were significantly higher in female liver and kidney. PABG was higher in female liver tissue but lower in kidney compared to male tissues. In addition, qPCR of mRNA extracted from liver tissue suggested a significantly lower level of Nat2 expression in female animals. Deletion of Nat2 affected liver 5- methyl-tetrahydrofolate in female mice but had little effect on other components of the methionine-S-adenosylmethionine cycle. No N-acetyl-PABG was observed in any tissues in Nat2 null mice, consistent with the role of Nat2 in PABG acetylation. Surprisingly, tissue PABG levels were similar between wild type and Nat2 null mice. These results show that Nat2 is not required to maintain tissue PABG homeostasis in vivo under normal conditions.

  14. Endoplasmic reticulum stress-responsive transcription factor ATF6α directs recruitment of the Mediator of RNA polymerase II transcription and multiple histone acetyltransferase complexes.

    Science.gov (United States)

    Sela, Dotan; Chen, Lu; Martin-Brown, Skylar; Washburn, Michael P; Florens, Laurence; Conaway, Joan Weliky; Conaway, Ronald C

    2012-06-29

    The basic leucine zipper transcription factor ATF6α functions as a master regulator of endoplasmic reticulum (ER) stress response genes. Previous studies have established that, in response to ER stress, ATF6α translocates to the nucleus and activates transcription of ER stress response genes upon binding sequence specifically to ER stress response enhancer elements in their promoters. In this study, we investigate the biochemical mechanism by which ATF6α activates transcription. By exploiting a combination of biochemical and multidimensional protein identification technology-based mass spectrometry approaches, we have obtained evidence that ATF6α functions at least in part by recruiting to the ER stress response enhancer elements of ER stress response genes a collection of RNA polymerase II coregulatory complexes, including the Mediator and multiple histone acetyltransferase complexes, among which are the Spt-Ada-Gcn5 acetyltransferase (SAGA) and Ada-Two-A-containing (ATAC) complexes. Our findings shed new light on the mechanism of action of ATF6α, and they outline a straightforward strategy for applying multidimensional protein identification technology mass spectrometry to determine which RNA polymerase II transcription factors and coregulators are recruited to promoters and other regulatory elements to control transcription.

  15. Primary structure of the human M2 mitochondrial autoantigen of primary biliary cirrhosis: Dihydrolipoamide acetyltransferase

    International Nuclear Information System (INIS)

    Coppel, R.L.; McNeilage, L.J.; Surh, C.D.; Van De Water, J.; Spithill, T.W.; Whittingham, S.; Gershwin, M.E.

    1988-01-01

    Primary biliary cirrhosis is a chronic, destructive autoimmune liver disease of humans. Patient sera are characterized by a high frequency of autoantibodies to a M r 70,000 mitochondrial antigen a component of the M2 antigen complex. The authors have identified a human cDNA clone encoding the complete amino acid sequence of this autoantigen. The predicted structure has significant similarity with the dihydrolipoamide acetyltransferase of the Escherichia coli pyruvate dehydrogenase multienzyme complex. The human sequence preserves the Glu-Thr-Asp-Lys-Ala motif of the lipoyl-binding site and has two potential binding sites. Expressed fragments of the cDNA react strongly with sera from patients with primary biliary cirrhosis but not with sera from patients with autoimmune chronic active hepatitis or sera from healthy subjects

  16. Genetic polymorphisms of N-acetyltransferase 2 & susceptibility to antituberculosis drug-induced hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Surendra K Sharma

    2016-01-01

    Full Text Available Background & objectives: The N-acetyltransferase 2 (NAT2 gene encodes an enzyme which both activates and deactivates arylamine and other drugs and carcinogens. This study was aimed to investigate the role of NAT2 gene polymorphism in anti-tuberculosis drug-induced hepatotoxicity (DIH. Methods: In this prospective study, polymerase chain reaction-restriction fragment length polymorphism results for NAT2 gene were compared between 185 tuberculosis patients who did not develop DIH and 105 tuberculosis patients who developed DIH while on anti-tuberculosis drugs. Results: Frequency of slow-acetylator genotype was commonly encountered and was not significantly different between DIH (82.8% and non-DIH (77.2% patients. However, the genotypic distribution of variant NAT2FNx015/FNx017 amongst slow-acetylator genotypes was significantly higher in DIH (56% group as compared to non-DIH (39% group (odds ratio 2.02; P=0.006. Interpretation & conclusions: The present study demonstrated no association between NAT2 genotype and DIH in the north Indian patients with tuberculosis.

  17. Crystal Structures of Murine Carnitine Acetyltransferase in Ternary Complexes with Its Substrates

    Energy Technology Data Exchange (ETDEWEB)

    Hsiao,Y.; Jogl, G.; Tong, L.

    2006-01-01

    Carnitine acyltransferases catalyze the reversible exchange of acyl groups between coenzyme A (CoA) and carnitine. They have important roles in many cellular processes, especially the oxidation of long-chain fatty acids in the mitochondria for energy production, and are attractive targets for drug discovery against diabetes and obesity. To help define in molecular detail the catalytic mechanism of these enzymes, we report here the high resolution crystal structure of wild-type murine carnitine acetyltransferase (CrAT) in a ternary complex with its substrates acetyl-CoA and carnitine, and the structure of the S554A/M564G double mutant in a ternary complex with the substrates CoA and hexanoylcarnitine. Detailed analyses suggest that these structures may be good mimics for the Michaelis complexes for the forward and reverse reactions of the enzyme, representing the first time that such complexes of CrAT have been studied in molecular detail. The structural information provides significant new insights into the catalytic mechanism of CrAT and possibly carnitine acyltransferases in general.

  18. Effect of hyperbaric oxygen on lipid peroxidation and visual development in neonatal rats with hypoxia-ischemia brain damage.

    Science.gov (United States)

    Chen, Jing; Chen, Yan-Hui; Lv, Hong-Yan; Chen, Li-Ting

    2016-07-01

    The aim of the present study was to investigate the effect of hyperbaric oxygen (HBO) on lipid peroxidation and visual development in a neonatal rat model of hypoxic-ischemic brain damage (HIBD). The rat models of HIBD were established by delayed uterus dissection and were divided randomly into two groups (10 rats each): HIBD and HBO-treated HIBD (HIBD+HBO) group. Another 20 rats that underwent sham-surgery were also divided randomly into the HBO-treated and control groups. The rats that underwent HBO treatment received HBO (0.02 MPa, 1 h/day) 24 h after the surgery and this continued for 14 days. When rats were 4 weeks old, their flash visual evoked potentials (F-VEPs) were monitored and the ultrastructures of the hippocampus were observed under transmission electron microscope. The levels of superoxide dismutase (SOD) and malonyldialdehyde (MDA) in the brain tissue homogenate were detected by xanthine oxidase and the thiobarbituric acid colorimetric method. Compared with the control group, the ultrastructures of the pyramidal neurons in the hippocampal CA3 area were distorted, the latencies of F-VEPs were prolonged (P0.05). HBO enhances antioxidant capacity and reduces the ultrastructural damage induced by hypoxic-ischemia, which may improve synaptic reconstruction and alleviate immature brain damage to promote the habilitation of brain function.

  19. Effects of hyperbaric oxygen and irradiation on experimental skin flaps in rats

    International Nuclear Information System (INIS)

    Nemiroff, P.M.; Merwin, G.E.; Brant, T.; Cassisi, N.J.

    1985-01-01

    This study investigated the effects of hyperbaric oxygen (HBO) and irradiation (RT) on experimental skin flaps in rats under varying conditions. Animals were assigned at random to 1 of 15 groups that represented all possible ordering effects of HBO, RT, and flap, as well as controls that included flap-only, RT-only, and HBO-only groups. Cranially based skin flaps measuring 3 x 9 cm were elevated on the dorsum. The surviving length was evaluated with fluorescein dye 7 days after the operation. Depending on the treatment condition, HBO was given either 48 hours or 24 hours before flap elevation, or within 4 hours or 48 hours after flap elevation. Rats receiving RT ( 60 Co) were given a single dose of 1000 rads to the dorsum. Results showed that all groups receiving HBO within 4 hours after flap elevation had significantly greater flap survival length, with as much as a 22% greater length of surviving flap. HBO given 48 hours before flap elevation also significantly improved flap survival over controls. RT appeared to have no immediate significant effect on flap survival. However, rats receiving RT, regardless of other factors, gained significantly less weight than did controls. Findings clearly indicate that, to be effective, HBO needs to be given as soon after surgery as possible

  20. Yeast Sgf73/Ataxin-7 serves to anchor the deubiquitination module into both SAGA and Slik(SALSA HAT complexes

    Directory of Open Access Journals (Sweden)

    Lee Kenneth K

    2009-02-01

    Full Text Available Abstract Spinocerebellar ataxia (SCA is a physically devastating, genetically inherited disorder characterized by abnormal brain function that results in the progressive loss of the ability to coordinate movements. There are many types of SCAs as there are various gene mutations that can cause this disease. SCA types 1–3, 6–10, 12, and 17 result from a trinucleotide repeat expansion in the DNA-coding sequence. Intriguingly, recent work has demonstrated that increased trinucleotde expansions in the SCA7 gene result in defect in the function of the SAGA histone acetyltransferase complex. The SCA7 gene encodes a subunit of the SAGA complex. This subunit is conserved in yeast as the SGF73 gene. We demonstrate that Sgf73 is required to recruit the histone deubiquitination module into both SAGA and the related SliK(SALSA complex, and to maintain levels of histone ubiquitination, which is necessary for regulation of transcription at a number of genes.

  1. Chromatin-regulating proteins as targets for cancer therapy

    International Nuclear Information System (INIS)

    Oike, Takahiro; Ogiwara, Hideaki; Kohno, Takashi; Amornwichet, Napapat; Nakano, Takashi

    2014-01-01

    Chromatin-regulating proteins represent a large class of novel targets for cancer therapy. In the context of radiotherapy, acetylation and deacetylation of histones by histone acetyltransferases (HATs) and histone deacetylases (HDACs) play important roles in the repair of DNA double-strand breaks generated by ionizing irradiation, and are therefore attractive targets for radiosensitization. Small-molecule inhibitors of HATs (garcinol, anacardic acid and curcumin) and HDACs (vorinostat, sodium butyrate and valproic acid) have been shown to sensitize cancer cells to ionizing irradiation in preclinical models, and some of these molecules are being tested in clinical trials, either alone or in combination with radiotherapy. Meanwhile, recent large-scale genome analyses have identified frequent mutations in genes encoding chromatin-regulating proteins, especially in those encoding subunits of the SWI/SNF chromatin-remodeling complex, in various human cancers. These observations have driven researchers toward development of targeted therapies against cancers carrying these mutations. DOT1L inhibition in MLL-rearranged leukemia, EZH2 inhibition in EZH2-mutant or MLL-rearranged hematologic malignancies and SNF5-deficient tumors, BRD4 inhibition in various hematologic malignancies, and BRM inhibition in BRG1-deficient tumors have demonstrated promising anti-tumor effects in preclinical models, and these strategies are currently awaiting clinical application. Overall, the data collected so far suggest that targeting chromatin-regulating proteins is a promising strategy for tomorrow's cancer therapy, including radiotherapy and molecularly targeted chemotherapy. (author)

  2. Sampling of BTX in Hat Yai city using cost effective laboratory-built PCB passive sampler.

    Science.gov (United States)

    Subba, Jas Raj; Thammakhet, Chongdee; Thavarungkul, Panote; Kanatharana, Proespichaya

    2016-08-23

    A laboratory-built printed circuit board (PCB) passive sampler used for the monitoring of xylene and styrene in copy print shops was re-validated for detecting benzene, toluene and xylene (BTX) and applied for the sampling of ambient air from Hat Yai city, Songkhla, Thailand, in the month of November 2014. For monitoring, the PCB passive samplers were exposed to target analytes in 16 locations covering high to low exposure areas. After sampling, the samplers were thermally desorbed and the analytes were trapped by multi-walled carbon nanotubes packed into a micro-preconcentrator coupled to a gas chromatograph (GC) equipped with a flame ionization detector. At the optimum GC operating conditions, the linear dynamic ranges for BTX were 0.06-5.6 µg for benzene, 0.07-2.2 µg for toluene and 0.23-2.5 µg for xylene with R(2) > 0.99 with the limits of detection being 6.6, 6.8 and 19 ng for benzene, toluene and xylene, respectively. The concentrations of BTX in the 16 sampling sites were in the range of N.D.-1.3 ± 1.6, 4.50 ± 0.76-49.6 ± 3.7 and 1.00 ± 0.21-39.6 ± 3.1 µg m(-3), respectively. When compared to past studies, there had been an increase in the benzene concentration.

  3. Arylamine N-acetyltransferase activity in bronchial epithelial cells and its inhibition by cellular oxidants

    International Nuclear Information System (INIS)

    Dairou, Julien; Petit, Emile; Ragunathan, Nilusha; Baeza-Squiban, Armelle; Marano, Francelyne; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

    2009-01-01

    Bronchial epithelial cells express xenobiotic-metabolizing enzymes (XMEs) that are involved in the biotransformation of inhaled toxic compounds. The activities of these XMEs in the lung may modulate respiratory toxicity and have been linked to several diseases of the airways. Arylamine N-acetyltransferases (NAT) are conjugating XMEs that play a key role in the biotransformation of aromatic amine pollutants such as the tobacco-smoke carcinogens 4-aminobiphenyl (4-ABP) and β-naphthylamine (β-NA). We show here that functional human NAT1 or its murine counterpart Nat2 are present in different lung epithelial cells i.e. Clara cells, type II alveolar cells and bronchial epithelial cells, thus indicating that inhaled aromatic amines may undergo NAT-dependent biotransformation in lung epithelium. Exposure of these cells to pathophysiologically relevant amounts of oxidants known to contribute to lung dysfunction, such as H 2 O 2 or peroxynitrite, was found to impair the NAT1/Nat2-dependent cellular biotransformation of aromatic amines. Genetic and non genetic impairment of intracellular NAT enzyme activities has been suggested to compromise the important detoxification pathway of aromatic amine N-acetylation and subsequently to contribute to an exacerbation of untoward effects of these pollutants on health. Our study suggests that oxidative/nitroxidative stress in lung epithelial cells, due to air pollution and/or inflammation, could contribute to local and/or systemic dysfunctions through the alteration of the functions of pulmonary NAT enzymes.

  4. Genetic variants in the choline acetyltransferase (ChAT) gene are modestly associated with normal cognitive function in the elderly

    DEFF Research Database (Denmark)

    Mengel-From, J; Christensen, K; Thinggaard, M

    2011-01-01

    Genetic variants in the choline acetyltransferase (ChAT) gene have been suggested as risk factors for neurodegenerative Alzheimer's disease (AD). Here we tested the importance of genetic variants in the ChAT gene in normal cognitive function of elderly in a study sample of Danish twins...... and singletons (N = 2070). The ChAT rs3810950 A allele, which has been associated with increased risk for AD, was found to be associated with a decrease cognitive status evaluated by a five-component cognitive composite score [P = 0.03, regression coefficient -0.30, 95% confidence interval (CI) -0.57 to -0...

  5. [Detection of human parvovirus B19, human bocavirus and human parvovirus 4 infections in blood samples among 95 patients with liver disease in Nanjing by nested PCR].

    Science.gov (United States)

    Tong, Rui; Zhou, Wei-Min; Liu, Xi-Jun; Wang, Yue; Lou, Yong-Liang; Tan, Wen-Jie

    2013-04-01

    To analyze the infection of human parvovirus B19, human bocavirus (HBoV) and human parvovirus 4 (PARV4) in blood samples among patients with liver disease in Nanjing by molecular detection. Nested PCR assays were designed and validated to detect B19, HBoV and PARV4, respectively. The assays were used to screen three parvoviruses in blood samples from 95 patients with different liver disease in Nanjing. The parvovirus infection was analyzed statistically. The detection limits were 10 copies of genomic DNA equivalents per reaction for each assays and the good specificity were observed. The frequency of B19 and HBoV were 2/95 (2.1%) and 9/95 (9.5%) in blood samples respectively. No PARV4 was detected. HBoV was detected in 3/5 patients with drug-induced hepatitis. Both B19 and HBoV infection were detected in blood from patients with liver disease.

  6. Hydrogen gas alleviates oxygen toxicity by reducing hydroxyl radical levels in PC12 cells.

    Directory of Open Access Journals (Sweden)

    Junchao Yu

    Full Text Available Hyperbaric oxygen (HBO therapy through breathing oxygen at the pressure of above 1 atmosphere absolute (ATA is useful for varieties of clinical conditions, especially hypoxic-ischemic diseases. Because of generation of reactive oxygen species (ROS, breathing oxygen gas at high pressures can cause oxygen toxicity in the central nervous system, leading to multiple neurological dysfunction, which limits the use of HBO therapy. Studies have shown that Hydrogen gas (H2 can diminish oxidative stress and effectively reduce active ROS associated with diseases. However, the effect of H2 on ROS generated from HBO therapy remains unclear. In this study, we investigated the effect of H2 on ROS during HBO therapy using PC12 cells. PC12 cells cultured in medium were exposed to oxygen gas or mixed oxygen gas and H2 at 1 ATA or 5 ATA. Cells viability and oxidation products and ROS were determined. The data showed that H2 promoted the cell viability and inhibited the damage in the cell and mitochondria membrane, reduced the levels of lipid peroxidation and DNA oxidation, and selectively decreased the levels of •OH but not disturbing the levels of O2•-, H2O2, or NO• in PC12 cells during HBO therapy. These results indicated that H2 effectively reduced •OH, protected cells against oxygen toxicity resulting from HBO therapy, and had no effect on other ROS. Our data supported that H2 could be potentially used as an antioxidant during HBO therapy.

  7. Radiological audit of remedial action activities at the processing sites Mexican Hat, Utah and Monument Valley, Arizona. Audit date: May 3--7, 1993, Final report

    International Nuclear Information System (INIS)

    1993-05-01

    The Uranium Mill Tailings Remedial Action (UMTRA) Project's Technical Assistance Contractor (TAC) performed a radiological audit of the Remedial Action Contractor (RAC), MK-Ferguson and CWM Federal Environmental Services, Inc., at the processing sites in Mexican Hat, Utah, and Monument Valley, Arizona. This audit was conducted May 3--7, 1993, by Bill James and Gerry Simiele of the TAC. Three site-specific findings and four observations were identified during the audit and are presented in this report. The overall conclusion from the audit is that the majority of the radiological aspects of the Mexican Hat, Utah, and Monument Valley, Arizona, remedial action programs are performed adequately. However, the findings identify that there is some inconsistency in following procedures and meeting requirements for contamination control, and a lack of communication between the RAC and the DOE on variances from the published remedial action plan (RAP)

  8. Directional Migration in Esophageal Squamous Cell Carcinoma (ESCC) is Epigenetically Regulated by SET Nuclear Oncogene, a Member of the Inhibitor of Histone Acetyltransferase Complex

    OpenAIRE

    Xiang Yuan; Xinshuai Wang; Bianli Gu; Yingjian Ma; Yiwen Liu; Man Sun; Jinyu Kong; Wei Sun; Huizhi Wang; Fuyou Zhou; Shegan Gao

    2017-01-01

    Directional cell migration is of fundamental importance to a variety of biological events, including metastasis of malignant cells. Herein, we specifically investigated SET oncoprotein, a subunit of the recently identified inhibitor of acetyltransferases (INHAT) complex and identified its role in the establishment of front–rear cell polarity and directional migration in Esophageal Squamous Cell Carcinoma (ESCC). We further define the molecular circuits that govern these processes by showing t...

  9. Peroxisome proliferator-activated receptor gamma and spermidine/spermine N1-acetyltransferase gene expressions are significantly correlated in human colorectal cancer

    International Nuclear Information System (INIS)

    Linsalata, Michele; Giannini, Romina; Notarnicola, Maria; Cavallini, Aldo

    2006-01-01

    The peroxisome proliferator-activated receptor γ (PPARγ) is a transcription factor that regulates adipogenic differentiation and glucose homeostasis. Spermidine/spermine N 1 -acetyltransferase (SSAT) and ornithine decarboxylase (ODC) are key enzymes involved in the metabolism of polyamines, compounds that play an important role in cell proliferation. While the PPARγ role in tumour growth has not been clearly defined, the involvement of the altered polyamine metabolism in colorectal carcinogenesis has been established. In this direction, we have evaluated the PPARγ expression and its relationship with polyamine metabolism in tissue samples from 40 patients operated because of colorectal carcinoma. Since it is known that the functional role of K-ras mutation in colorectal tumorigenesis is associated with cell growth and differentiation, polyamine metabolism and the PPARγ expression were also investigated in terms of K-ras mutation. PPARγ, ODC and SSAT mRNA levels were evaluated by reverse transcriptase and real-time PCR. Polyamines were quantified by high performance liquid chromatography (HPLC). ODC and SSAT activity were measured by a radiometric technique. PPARγ expression, as well as SSAT and ODC mRNA levels were significantly higher in cancer as compared to normal mucosa. Tumour samples also showed significantly higher polyamine levels and ODC and SSAT activities in comparison to normal samples. A significant and positive correlation between PPARγ and the SSAT gene expression was observed in both normal and neoplastic tissue (r = 0.73, p < 0.0001; r = 0.65, p < 0.0001, respectively). Moreover, gene expression, polyamine levels and enzymatic activities were increased in colorectal carcinoma samples expressing K-ras mutation as compared to non mutated K-ras samples. In conclusion, our data demonstrated a close relationship between PPARγ and SSAT in human colorectal cancer and this could represent an attempt to decrease polyamine levels and to reduce cell

  10. The first successful laparoscopic Whipple procedure at Hat Yai Hospital: surgical technique and a case report.

    Science.gov (United States)

    Khaimook, Araya; Borkird, Jumpot; Alapach, Sakda

    2010-09-01

    Whipple procedure is the most complex abdominal surgical procedure to treat periampullary carcinoma. With the benefit of minimally invasive approach, many institutes attempt to do Whipple procedure laparoscopically. However, only 146 cases of laparoscopic Whipple procedure have yet been reported in the literature worldwide between 1994 and 2008. The authors reported the first laparoscopic Whipple procedure at Hat Yai Hospital in December 2009. The patient was a 40-year-old, Thai-Muslim female, with the diagnosis of ampullary carcinoma. The operating time was 685 minutes. The patient was discharged on postoperative day 14 without serious complication. The surgical technique and postoperative progress of the patient were described.

  11. Investigation of endocrine and immunological response in fat tissue to hyperbaric oxygen administration in rats.

    Science.gov (United States)

    Şen, H; Erbağ, G; Ovali, M A; Öztopuz, R Ö; Uzun, M

    2016-04-30

    Though HBO treatment is becoming more common, the mechanism of action is not fully known. The positive effects of HBO administration on the inflammatory response is thought to be a possible basic mechanism. As a result, we aimed to research whether endocrine and immunological response of fat tissue changes in rats given HBO treatment model. This research was carried out on Wistar albino rats, they were treated with hyperbaric oxygen therapy. Their fatty tissue were taken from the abdomen, gene expression of the cytokines and adipokines were analyzed with Real time PCR method. When the gene expression of hormones and cytokines by fat tissue was examined, the leptin, visfatin, TNF-α, IL-1β and IL-10 levels in the HBO treatment group were statistically significantly increased compared to the control group (p=0.0313, p=0.0156, p=0.0156, p=0.0156, p=0.0313). In conclusion, in our study we identified that HBO administration affected the endochrinological functions of fat tissue.

  12. Detection of Human Bocavirus DNA by Multiplex PCR Analysis: Postmortem Case Report

    Directory of Open Access Journals (Sweden)

    Nihan Ziyade

    2015-06-01

    Full Text Available Background: Human bocavirus (HBoV is a virus belonging to the Parvoviridae family, which has been newly discovered to be associated with respiratory tract infections in children. There are many reports worldwide on the endemicity of this virus. Since it is relatively new, it is not routinely detected in clinical laboratory investigations. Case Report: We demonstrated that HBoV infection caused the death of a 5-month-old girl with a history of high fever and wheezing. Human bocavirus (HBoV 1/2/3/4 was found in a nasopharyngeal swab, paraffin-embedded lung tissue and stool samples by multiplex PCR methods using postmortem microbiological analysis. Conclusion: This case suggests that lower respiratory tract infections due to HBoV may cause severe and life-threatening diseases. Postmortem microbiology is useful in both clinical and forensic autopsies, and allows a suspected infection to be confirmed. To our knowledge, this report is the first document of a HBoV postmortem case in Turkey.

  13. Alteration of striatal dopamine levels under various partial pressure of oxygen in pre-convulsive and convulsive phases in freely-moving rats.

    Science.gov (United States)

    Lavoute, Cécile; Weiss, Michel; Risso, Jean-Jacques; Rostain, Jean-Claude

    2014-02-01

    The purpose of this study was to investigate the change in the striatal dopamine (DA) level in freely-moving rat exposed to different partial pressure of oxygen (from 1 to 5 ATA). Some works have suggested that DA release by the substantia nigra pars compacta (SNc) neurons in the striatum could be disturbed by hyperbaric oxygen (HBO) exposure, altering therefore the basal ganglia activity. Such changes could result in a change in glutamatergic and GABAergic control of the dopaminergic neurons into the SNc. Such alterations could provide more information about the oxygen-induced seizures observed at 5 ATA in rat. DA-sensitive electrodes were implanted into the striatum under general anesthesia. After 1 week rest, awaked rats were exposed to oxygen-nitrogen mixture at a partial pressure of oxygen of 1, 2, 3, 4 and 5 ATA. DA level was monitored continuously (every 3 min) by in vivo voltammetry before and during HBO exposure. HBO induced a decrease in DA level in relationship to the increase in partial pressure of oxygen from 1 ATA to 4 ATA (-15 % at 1 ATA, -30 % at 2 ATA, -40 % at 3 ATA, -45 % at 4 ATA), without signs of oxygen toxicity. At 5 ATA, DA level strongly decreases (-75 %) before seizure which occurred after 27 min ± 7 HBO exposure. After the epileptic seizure the decrease in DA level disappeared. These changes and the biphasic effect of HBO were discussed in function of HBO action on neurochemical regulations of the nigro striatal pathway.

  14. In vitro inhibition of choline acetyltransferase by a series of 2-benzylidene-3-quinuclidinones

    International Nuclear Information System (INIS)

    Capacio, B.R.

    1988-01-01

    Ten substituted 2-benzylidene-3-quinuclidinones were synthesized and evaluated for their relative potency as in vitro inhibitors of choline acetyltransferase (ChAT). Acetylcholine (ACh) synthesis was followed radiometrically by the incorporation of labeled acetate originating from 14 C-acetyl-CoA. Woolf-Augustinsson-Hofstee data analysis was used to calculate Vmax, Km, and Ki values. The inhibition was found to be noncompetitive or uncompetitive with respect to choline. Quantitative structure activity relationship correlations demonstrated a primary dependence on κ-σ, as well as steric properties of the substituted benzene ring. Additional radiometric and spectrophotometric were performed with 2-(3'-methyl)-benzylidene-3-quinuclidinone, one of the more potent analogs, to further elucidate the inhibitory mechanism. ChAT-mediated cleavage of ACh was measured spectrophotometrically by following the appearance of NADH at 340 nanometers in an enzyme coupled assay. Lineweaver-Burk analysis indicated mixed or uncompetitive inhibition with respect to both substrates of the forward reaction, suggesting interference with a rate limiting step

  15. N-acetyltransferase 2 gene polymorphism and presbycusis.

    Science.gov (United States)

    Unal, Murat; Tamer, Lülüfer; Doğruer, Zeynep Nil; Yildirim, Hatice; Vayisoğlu, Yusuf; Camdeviren, Handan

    2005-12-01

    The enzyme of N-acetyltransferase (NAT) is involved in the metabolism and detoxification of cytotoxic and carcinogenic compounds as well as reactive oxygen species (ROS). The excessive amount of ROS generation occurs in the ageing inner ear. The exact etiopathogenesis of presbycusis is not known, but it is generally accepted that it is the result of series of insults, such as physiologic age-related degeneration, noise exposure, medical disorders and their treatment, as well as hereditary susceptibility. The effect of aging shows a wide interindividual range; we aimed to investigate whether profiles of NAT2 genotypes may be associated with the risk of presbycusis. Hospital-based, case-control study. We examined 68 adults with presbycusis and 98 healthy controls. DNA was extracted from whole blood, and the polymorphisms of NAT2*5A, NAT2*6A, NAT2*7A/B, and NAT2*14A were determined using a real-time polymerase chain reaction and fluorescence resonance energy transfer with a Light-Cycler Instrument. Associations between specific genotypes and the development of presbycusis were examined by use of logistic regression analyses to calculate odds ratios and 95% confidence intervals. Gene polymorphisms at NAT2*5A, NAT2*7A/B, and NAT2*14A in subjects with presbycusis were not significantly different from in the controls (P > .05). However, in NAT2*6A, the risk of presbycusis was 15.2-fold more in individuals with mutant allele than subjects with wild genotype (P = .013). Individuals with NAT2*6A heterozygote allele had a 0.34-fold less risk in the development of presbycusis than subjects with mutant allele (P = .032) We demonstrated a significant association between the NAT2*6A polymorphism and age-related hearing loss in this population. However, the sample size was relatively small, and further studies need to investigate the exact role of NAT2 gene polymorphism in the etiopathogenesis of the presbycusis.

  16. Effects of normobaric versus hyperbaric oxygen on cell injury induced by oxygen and glucose deprivation in acute brain slices

    Directory of Open Access Journals (Sweden)

    Laurent Chazalviel

    2016-01-01

    Full Text Available Normobaric oxygen (NBO and hyperbaric oxygen (HBO are emerging as a possible co-treatment of acute ischemic stroke. Both have been shown to reduce infarct volume, to improve neurologic outcome, to promote endogenous tissue plasminogen activator-induced thrombolysis and cerebral blood flow, and to improve tissue oxygenation through oxygen diffusion in the ischemic areas, thereby questioning the interest of HBO compared to NBO. In the present study, in order to investigate and compare the oxygen diffusion effects of NBO and HBO on acute ischemic stroke independently of their effects at the vascular level, we used acute brain slices exposed to oxygen and glucose deprivation, an ex vivo model of brain ischemia that allows investigating the acute effects of NBO (partial pressure of oxygen (pO 2 = 1 atmospheres absolute (ATA = 0.1 MPa and HBO (pO 2 = 2.5 ATA = 0.25 MPa through tissue oxygenation on ischemia-induced cell injury as measured by the release of lactate dehydrogenase. We found that HBO, but not NBO, reduced oxygen and glucose deprivation-induced cell injury, indicating that passive tissue oxygenation (i.e. without vascular support of the brain parenchyma requires oxygen partial pressure higher than 1 ATA.

  17. Kinetic characterisation of arylamine N-acetyltransferase from Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Sim Edith

    2007-03-01

    Full Text Available Abstract Background Arylamine N-acetyltransferases (NATs are important drug- and carcinogen-metabolising enzymes that catalyse the transfer of an acetyl group from a donor, such as acetyl coenzyme A, to an aromatic or heterocyclic amine, hydrazine, hydrazide or N-hydroxylamine acceptor substrate. NATs are found in eukaryotes and prokaryotes, and they may also have an endogenous function in addition to drug metabolism. For example, NAT from Mycobacterium tuberculosis has been proposed to have a role in cell wall lipid biosynthesis, and is therefore of interest as a potential drug target. To date there have been no studies investigating the kinetic mechanism of a bacterial NAT enzyme. Results We have determined that NAT from Pseudomonas aeruginosa, which has been described as a model for NAT from M. tuberculosis, follows a Ping Pong Bi Bi kinetic mechanism. We also describe substrate inhibition by 5-aminosalicylic acid, in which the substrate binds both to the free form of the enzyme and the acetyl coenzyme A-enzyme complex in non-productive reaction pathways. The true kinetic parameters for the NAT-catalysed acetylation of 5-aminosalicylic acid with acetyl coenzyme A as the co-factor have been established, validating earlier approximations. Conclusion This is the first reported study investigating the kinetic mechanism of a bacterial NAT enzyme. Additionally, the methods used herein can be applied to investigations of the interactions of NAT enzymes with new chemical entities which are NAT ligands. This is likely to be useful in the design of novel potential anti-tubercular agents.

  18. Transfection of cultured cells of the cotton boll weevil, Anthonomus grandis, with a heat-shock-promoter-chloramphenicol-acetyltransferase construct.

    Science.gov (United States)

    Stiles, B; Heilmann, J; Sparks, R B; Santoso, A; Leopold, R A

    1992-01-01

    Expression of heat shock proteins (hsp) in the BRL-AG-3C cell line from the cotton boll weevil was examined. It was determined that the maximal expression of endogenous hsp occurred at 41 degrees C. Various transfection methods were then compared using this cell line in conjunction with a transiently expressed bacterial gene marker (chloramphenicol acetyltransferase) which was under the control of the Drosophila hsp 70 gene promoter. The cationic lipid preparation Lipofectin was found to be very efficient at transfecting the boll weevil cells. Polylysine and 20-hydroxyecdysone-conjugated polylysine were moderately effective, whereas polybrene and electroporation, under the conditions reported herein, were ineffective at transfecting this cell line.

  19. Ubiquitylation of the acetyltransferase MOF in Drosophila melanogaster.

    Science.gov (United States)

    Schunter, Sarah; Villa, Raffaella; Flynn, Victoria; Heidelberger, Jan B; Classen, Anne-Kathrin; Beli, Petra; Becker, Peter B

    2017-01-01

    The nuclear acetyltransferase MOF (KAT8 in mammals) is a subunit of at least two multi-component complexes involved in transcription regulation. In the context of complexes of the 'Non-Specific-Lethal' (NSL) type it controls transcription initiation of many nuclear housekeeping genes and of mitochondrial genes. While this function is conserved in metazoans, MOF has an additional, specific function in Drosophila in the context of dosage compensation. As a subunit of the male-specific-lethal dosage compensation complex (MSL-DCC) it contributes to the doubling of transcription output from the single male X chromosome by acetylating histone H4. Proper dosage compensation requires finely tuned levels of MSL-DCC and an appropriate distribution of MOF between the regulatory complexes. The amounts of DCC formed depends directly on the levels of the male-specific MSL2, which orchestrates the assembly of the DCC, including MOF recruitment. We found earlier that MSL2 is an E3 ligase that ubiquitylates most MSL proteins, including MOF, suggesting that ubiquitylation may contribute to a quality control of MOF's overall levels and folding state as well as its partitioning between the complex entities. We now used mass spectrometry to map the lysines in MOF that are ubiquitylated by MSL2 in vitro and identified in vivo ubiquitylation sites of MOF in male and female cells. MSL2-specific ubiquitylation in vivo could not be traced due to the dominance of other, sex-independent ubiquitylation events and conceivably may be rare or transient. Expressing appropriately mutated MOF derivatives we assessed the importance of the ubiquitylated lysines for dosage compensation by monitoring DCC formation and X chromosome targeting in cultured cells, and by genetic complementation of the male-specific-lethal mof2 allele in flies. Our study provides a comprehensive analysis of MOF ubiquitylation as a reference for future studies.

  20. Ubiquitylation of the acetyltransferase MOF in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Sarah Schunter

    Full Text Available The nuclear acetyltransferase MOF (KAT8 in mammals is a subunit of at least two multi-component complexes involved in transcription regulation. In the context of complexes of the 'Non-Specific-Lethal' (NSL type it controls transcription initiation of many nuclear housekeeping genes and of mitochondrial genes. While this function is conserved in metazoans, MOF has an additional, specific function in Drosophila in the context of dosage compensation. As a subunit of the male-specific-lethal dosage compensation complex (MSL-DCC it contributes to the doubling of transcription output from the single male X chromosome by acetylating histone H4. Proper dosage compensation requires finely tuned levels of MSL-DCC and an appropriate distribution of MOF between the regulatory complexes. The amounts of DCC formed depends directly on the levels of the male-specific MSL2, which orchestrates the assembly of the DCC, including MOF recruitment. We found earlier that MSL2 is an E3 ligase that ubiquitylates most MSL proteins, including MOF, suggesting that ubiquitylation may contribute to a quality control of MOF's overall levels and folding state as well as its partitioning between the complex entities. We now used mass spectrometry to map the lysines in MOF that are ubiquitylated by MSL2 in vitro and identified in vivo ubiquitylation sites of MOF in male and female cells. MSL2-specific ubiquitylation in vivo could not be traced due to the dominance of other, sex-independent ubiquitylation events and conceivably may be rare or transient. Expressing appropriately mutated MOF derivatives we assessed the importance of the ubiquitylated lysines for dosage compensation by monitoring DCC formation and X chromosome targeting in cultured cells, and by genetic complementation of the male-specific-lethal mof2 allele in flies. Our study provides a comprehensive analysis of MOF ubiquitylation as a reference for future studies.

  1. Detection of human bocavirus from children and adults with acute respiratory tract illness in Guangzhou, southern China

    Directory of Open Access Journals (Sweden)

    Liu Wen-Kuan

    2011-12-01

    Full Text Available Abstract Background Human bocavirus (HBoV is a newly discovered parvovirus associated with acute respiratory tract illness (ARTI and gastrointestinal illness. Our study is the first to analyze the characteristics of HBoV-positive samples from ARTI patients with a wide age distribution from Guangzhou, southern China. Methods Throat swabs (n=2811 were collected and analyzed from children and adults with ARTI over a 13-month period. The HBoV complete genome from a 60 year-old female patient isolate was also determined. Results HBoV DNA was detected in 65/2811 (2.3% samples, of which 61/1797 were from children (Mycoplasma pneumoniae had the highest frequency of 16.9% (11/65. Upper and lower respiratory tract illness were common symptoms, with 19/65 (29.2% patients diagnosed with pneumonia by chest radiography. All four adult patients had systemic influenza-like symptoms. Phylogenetic analysis of the complete genome revealed a close relationship with other HBoVs, and a more distant relationship with HBoV2 and HBoV3. Conclusions HBoV was detected from children and adults with ARTI from Guangzhou, southern China. Elderly people were also susceptive to HBoV. A single lineage of HBoV was detected among a wide age distribution of patients with ARTI.

  2. Combining hypobaric hypoxia or hyperbaric oxygen postconditioning with memantine reduces neuroprotection in 7-day-old rat hypoxia-ischemia.

    Science.gov (United States)

    Gamdzyk, Marcin; Ziembowicz, Apolonia; Bratek, Ewelina; Salinska, Elzbieta

    2016-10-01

    Perinatal hypoxia-ischemia causes brain injury in neonates, but a fully successful treatment to prevent changes in the brain has yet to be developed. The aim of this study was to evaluate the effect of combining memantine treatment with HBO (2.5 ATA) or HH (0.47 ATA) on neonatal hypoxia-ischemia brain injury. 7-day old rats were subjected to hypoxia-ischemia (H-I) and treated with combination of memantine and HBO or HH. The brain damage was evaluated by examination of infarct area and the number of apoptotic cells in CA1 region of hippocampus. Additionally, the level of reactive oxygen species (ROS) was measured. Memantine, HBO or HH postconditioning applied at short time (1-6h) after H-I, and repeated for two subsequent days, resulted in significant neuroprotection. The reduction in ipsilateral hemisphere weight deficit and in the size of infarct area was observed 14days after H-I. A reduction in apoptosis and ROS level was also observed. Combining memantine with HBO or HH resulted in a loss of neuroprotection. Our results show that, combining HBO or HH postconditioning with memantine produce no additive increase in the neuroprotective effect. On the contrary, combining the treatments resulted in lower neuroprotection in comparison to the effects of memantine, HBO or HH alone. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  3. No germline mutations in the histone acetyltransferase gene EP300 in BRCA1 and BRCA2 negative families with breast cancer and gastric, pancreatic, or colorectal cancer

    International Nuclear Information System (INIS)

    Campbell, Ian G; Choong, David; Chenevix-Trench, Georgia

    2004-01-01

    Mutations in BRCA1, BRCA2, ATM, TP53, CHK2 and PTEN account for many, but not all, multiple-case breast and ovarian cancer families. The histone acetyltransferase gene EP300 may function as a tumour suppressor gene because it is sometimes somatically mutated in breast, colorectal, gastric and pancreatic cancers, and is located on a region of chromosome 22 that frequently undergoes loss of heterozygosity in many cancer types. We hypothesized that germline mutations in EP300 may account for some breast cancer families that include cases of gastric, pancreatic and/or colorectal cancer. We screened the entire coding region of EP300 for mutations in the youngest affected members of 23 non-BRCA1/BRCA2 breast cancer families with at least one confirmed case of gastric, pancreatic and/or colorectal cancer. These families were ascertained in Australia through the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer. Denaturing HPLC analysis identified a heterozygous alteration at codon 211, specifically a GGC to AGC (glycine to serine) alteration, in two individuals. This conservative amino acid change was not within any known functional domains of EP300. The frequency of the Ser211 variant did not differ significanlty between a series of 352 breast cancer patients (4.0%) and 254 control individuals (2.8%; P = 0.5). The present study does not support a major role for EP300 mutations in breast and ovarian cancer families with a history of gastric, pancreatic and/or colorectal cancer

  4. Functional recovery in rat spinal cord injury induced by hyperbaric oxygen preconditioning.

    Science.gov (United States)

    Lu, Pei-Gang; Hu, Sheng-Li; Hu, Rong; Wu, Nan; Chen, Zhi; Meng, Hui; Lin, Jiang-Kai; Feng, Hua

    2012-12-01

    It is a common belief that neurosurgical interventions can cause inevitable damage resulting from the procedure itself in surgery especially for intramedullary spinal cord tumors. The present study was designed to examine if hyperbaric oxygen preconditioning (HBO-PC) was neuroprotective against surgical injuries using a rat model of spinal cord injury (SCI). Sprague-Dawley rats were randomly divided into three groups: HBO-PC group, hypobaric hypoxic preconditioning (HH-PC) control group, and normobaric control group. All groups were subjected to SCI by weight drop device. Rats from each group were examined for neurological behavior and electrophysiological function. Tissue sections were analyzed by using immunohistochemistry, TdT-mediated dUTP-biotin nick end labeling, and axonal tract tracing. Significant neurological deficits were observed after SCI and HBO-PC and HH-PC improved neurological deficits 1 week post-injury. The latencies of motor-evoked potential and somatosensory-evoked potential were significantly delayed after SCI, which was attenuated by HBO-PC and HH-PC. Compared with normobaric control group, pretreatment with HBO and hypobaric hypoxia significantly reduced the number of TdT-mediated dUTP-biotin nick end labeling-positive cells, and increased nestin-positive cells. HBO-PC and HH-PC enhanced axonal growth after SCI. In conclusion, preconditioning with HBO and hypobaric hypoxia can facilitate functional recovery and suppress cell apoptosis after SCI and may prove to be a useful preventive strategy to neurosurgical SCI.

  5. EPR Oximetry for Investigation of Hyperbaric O2 Pre-treatment for Tumor Radiosensitization.

    Science.gov (United States)

    Williams, Benjamin B; Hou, Huagang; Coombs, Rachel; Swartz, Harold M

    A number of studies have reported benefits associated with the application of hyperbaric oxygen treatment (HBO) delivered immediately prior to radiation therapy. While these studies provide evidence that pre-treatment with HBO may be beneficial, no measurements of intratumoral pO2 were carried out and they do not directly link the apparent benefits to decreased hypoxic fractions at the time of radiation therapy. While there is empirical evidence and some theoretical basis for HBO to enhance radiation therapy, without direct and repeated measurements of its effects on pO2, it is unlikely that the use of HBO can be understood and optimized for clinical applications. In vivo EPR oximetry is a technique uniquely capable of providing repeated direct measurements of pO2 through a non-invasive procedure in both animal models and human patients. In order to evaluate the ability of pretreatment with HBO to elevate tumor pO2, a novel small animal hyperbaric chamber system was constructed that allows simultaneous in vivo EPR oximetry. This chamber can be placed within the EPR magnet and is equipped with a variety of ports for multiplace gas delivery, thermoregulation, delivery of anesthesia, physiologic monitoring, and EPR detection. Initial measurements were performed in a subcutaneous RIF-1 tumor model in C3H/HeJ mice. The mean baseline pO2 value was 6.0 ± 1.2 mmHg (N = 7) and responses to two atmospheres absolute pressure HBO varied considerably across subjects, within tumors, and over time. When an increase in pO2 was observed, the effect was transient in all but one case, with durations lasting from 5 min to over 20 min, and returned to baseline levels during HBO administration. These results indicate that without direct measurements of pO2 in the tissue of interest, it is likely to be difficult to know the effects of HBO on actual tissue pO2.

  6. Human bocavirus infection as a cause of severe acute respiratory tract infection in children.

    Science.gov (United States)

    Moesker, F M; van Kampen, J J A; van der Eijk, A A; van Rossum, A M C; de Hoog, M; Schutten, M; Smits, S L; Bodewes, R; Osterhaus, A D M E; Fraaij, P L A

    2015-10-01

    In 2005 human bocavirus (HBoV) was discovered in respiratory tract samples of children. The role of HBoV as the single causative agent for respiratory tract infections remains unclear. Detection of HBoV in children with respiratory disease is frequently in combination with other viruses or bacteria. We set up an algorithm to study whether HBoV alone can cause severe acute respiratory tract infection (SARI) in children. The algorithm was developed to exclude cases with no other likely cause than HBoV for the need for admission to the paediatric intensive care unit (PICU) with SARI. We searched for other viruses by next-generation sequencing (NGS) in these cases and studied their HBoV viral loads. To benchmark our algorithm, the same was applied to respiratory syncytial virus (RSV)-positive patients. From our total group of 990 patients who tested positive for a respiratory virus by means of RT-PCR, HBoV and RSV were detected in 178 and 366 children admitted to our hospital. Forty-nine HBoV-positive patients and 72 RSV-positive patients were admitted to the PICU. We found seven single HBoV-infected cases with SARI admitted to PICU (7/49, 14%). They had no other detectable virus by NGS. They had much higher HBoV loads than other patients positive for HBoV. We identified 14 RSV-infected SARI patients with a single RSV infection (14/72, 19%). We conclude that our study provides strong support that HBoV can cause SARI in children in the absence of viral and bacterial co-infections. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  7. Sum of top-hat transform based algorithm for vessel enhancement in MRA images

    Science.gov (United States)

    Ouazaa, Hibet-Allah; Jlassi, Hajer; Hamrouni, Kamel

    2018-04-01

    The Magnetic Resonance Angiography (MRA) is rich with information's. But, they suffer from poor contrast, illumination and noise. Thus, it is required to enhance the images. But, these significant information can be lost if improper techniques are applied. Therefore, in this paper, we propose a new method of enhancement. We applied firstly the CLAHE method to increase the contrast of the image. Then, we applied the sum of Top-Hat Transform to increase the brightness of vessels. It is performed with the structuring element oriented in different angles. The methodology is tested and evaluated on the publicly available database BRAINIX. And, we used the measurement methods MSE (Mean Square Error), PSNR (Peak Signal to Noise Ratio) and SNR (Signal to Noise Ratio) for the evaluation. The results demonstrate that the proposed method could efficiently enhance the image details and is comparable with state of the art algorithms. Hence, the proposed method could be broadly used in various applications.

  8. Phenotypic variability in 49 cases of ESCO2 mutations, including novel missense and codon deletion in the acetyltransferase domain, correlates with ESCO2 expression and establishes the clinical criteria for Roberts syndrome

    DEFF Research Database (Denmark)

    Vega, H; Trainer, A H; Gordillo, M

    2010-01-01

    Roberts syndrome (RBS) and SC phocomelia are caused by mutations in ESCO2, which codes for an acetyltransferase involved in the regulation of sister chromatid cohesion. Of 26 mutations described to date, only one missense mutation has been reported and all others are predicted to be truncating...

  9. Phenotypic variability in 49 cases of ESCO2 mutations, including novel missense and codon deletion in the acetyltransferase domain, correlates with ESCO2 expression and establishes the clinical criteria for Roberts syndrome

    NARCIS (Netherlands)

    Vega, H.; Trainer, A.H.; Gordillo, M.; Crosier, M.; Kayserili, H.; Skovby, F.; Uzielli, M.L.G.; Schnur, R.E.; Manouvrier, S.; Blair, E.; Hurst, J.A.; Forzano, F.; Meins, M.; Simola, K.O.J.; Raas-Rothschild, A; Hennekam, R.C.M.; Jabs, E.W.

    2010-01-01

    Background Roberts syndrome (RBS) and SC phocomelia are caused by mutations in ESCO2, which codes for an acetyltransferase involved in the regulation of sister chromatid cohesion. Of 26 mutations described to date, only one missense mutation has been reported and all others are predicted to be

  10. Acetyl coenzyme A: alpha-glucosaminide N-acetyltransferase. Evidence for a transmembrane acetylation mechanism

    International Nuclear Information System (INIS)

    Bame, K.J.; Rome, L.H.

    1985-01-01

    The lysosomal membrane enzyme acetyl-CoA: alpha-glucosaminide N-acetyltransferase catalyzes the transfer of an acetyl group from acetyl-CoA to terminal alpha-linked glucosamine residues of heparan sulfate. The reaction mechanism was examined using highly purified lysosomal membranes from rat liver. The reaction was followed by measuring the acetylation of a monosaccharide acetyl acceptor, glucosamine. The enzyme reaction was optimal above pH 5.5, and a 2-3-fold stimulation of activity was observed when the membranes were assayed in the presence of 0.1% taurodeoxycholate. Double reciprocal analysis and product inhibition studies indicated that the enzyme works by a Di-Iso Ping Pong Bi Bi mechanism. Further evidence to support this mechanism was provided by characterization of the enzyme half-reactions. Membranes incubated with acetyl-CoA and [ 3 H]CoA were found to produce acetyl-[ 3 H]CoA. This exchange was optimal at pH values above 7.0. Treating membranes with [ 3 H] acetyl-CoA resulted in the formation of an acetyl-enzyme intermediate. The acetyl group could then be transferred to glucosamine, forming [ 3 H]N-acetylglucosamine. The transfer of the acetyl group from the enzyme to glucosamine was optimal between pH 4 and 5. The results suggest that acetyl-CoA does not cross the lysosomal membrane. Instead, the enzyme is acetylated on the cytoplasmic side of the lysosome and the acetyl group is then transferred to the inside where it is used to acetylate heparan sulfate

  11. Effect of acute and delayed hyperbaric oxygen therapy on cyanide whole blood levels during acute cyanide intoxication

    DEFF Research Database (Denmark)

    Lawson-Smith, P; Jansen, E C; Hilsted, Linda Maria

    2011-01-01

    and the subsequent formation of cyanocobalamin measured by a spectrophotometer. Results showed that whole-blood-cyanide concentration in Group 1 controls and acute HBO2 initially rose and then fell towards zero. In rats treated with delayed HBO2, the reduction in whole-blood-cyanide concentration was significantly...

  12. Cryospectrophotometric determination of tumor intravascular oxyhemoglobin saturations: dependence on vascular geometry and tumor growth.

    Science.gov (United States)

    Fenton, B M; Rofstad, E K; Degner, F L; Sutherland, R M

    1988-12-21

    To delineate the complex relationships between overall tumor oxygenation and vascular configuration, intravascular oxyhemoglobin (HbO2) saturation distributions were measured with cryospectrophotometric techniques. Four factors related to vascular morphometry and tumor growth were evaluated: a) vessel diameter, b) distance of vessel from the tumor surface, c) tumor volume, and d) vascular density. To measure intertumor heterogeneity, two murine sarcomas (RIF-1 and KHT) and two human ovarian carcinoma xenografts (OWI and MLS) were utilized. In contrast to skeletal muscle, a preponderance of very low HbO2 saturations was observed for both large and small tumors of all lines. Saturations up to about 90% were also generally present, however, even in very large tumors. Variations in vascular configuration were predominantly tumor-line dependent rather than due to inherent characteristics of the host vasculature, and widely disparate HbO2 distributions were found for alternate lines implanted in identical host mice. Although peripheral saturations remained fairly constant with tumor growth, HbO2 values were markedly lower for vessels nearer the tumor center and further decreased with increasing tumor volume. HbO2 saturations did not change substantially with increasing vascular density (except for KHT tumors), although density did decrease with increasing distance from tumor surface. Combined effects of vessel diameter, tumor volume, and vessel location on HbO2 saturations were complex and varied markedly with both tumor line and vessel class. For specific classes, HbO2 distributions correlated closely with radiobiological hypoxic fractions, i.e., for tumor lines in which hypoxic fraction increased substantially with tumor volume, corresponding HbO2 values decreased, while for lines in which hypoxic fraction remained constant, HbO2 values also were unchanged. Although these trends may also be a function of differing oxygen consumption rates between tumor lines

  13. ORF Alignment: NC_003282 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available NC_003282 gi|25145178 >1nm8A 15 591 29 627 e-131 ... gb|AAB88370.1| Abnormal choline ...acetyltransferase protein 1, isoform b ... [Caenorhabditis elegans] ref|NP_500387.2| choline ... ... ... acetyltransferase, abnormal CHoline Acetyltransferase ... CHA-1, UNCoordinated locomotion UNC-17 (...71.3 kD) ... (unc-17+cha-1) [Caenorhabditis elegans] pir||T37293 ... choli...ne O-acetyltransferase (EC 2.3.1.6) - ... Caenorhabditis elegans sp|P32756|CLAT_CAEEL Choline

  14. HAT-TR-318-007: A Double-lined M Dwarf Binary with Total Secondary Eclipses Discovered by HATNet and Observed by K2

    Science.gov (United States)

    Hartman, J. D.; Quinn, S. N.; Bakos, G. Á.; Torres, G.; Kovács, G.; Latham, D. W.; Noyes, R. W.; Shporer, A.; Fulton, B. J.; Esquerdo, G. A.; Everett, M. E.; Penev, K.; Bhatti, W.; Csubry, Z.

    2018-03-01

    We report the discovery by the HATNet survey of HAT-TR-318-007, a P=3.34395390+/- 0.00000020 day period detached double-lined M dwarf binary with total secondary eclipses. We combine radial velocity (RV) measurements from TRES/FLWO 1.5 m and time-series photometry from HATNet, FLWO 1.2 m, BOS 0.8 m, and NASA K2 Campaign 5, to determine the masses and radii of the component stars: MA=0.448+/-0.011 M⊙N, MB=0.2721-0.0042+0.0041 M⊙N, RA=0.4548-0.0036+0.0035 R⊙N, and RB=0.2913-0.0024+0.0023 R⊙N. We obtained a FIRE/Magellan near-infrared spectrum of the primary star during a total secondary eclipse, and we use this to obtain disentangled spectra of both components. We determine spectral types of STA=M 3.71+/- 0.69 and STB=M 5.01+/- 0.73 and effective temperatures of Teff, A= 3190+/-110 K and Teff, B=3100+/- 110 K for the primary and secondary star, respectively. We also measure a metallicity of [Fe/H] = +0.298+/- 0.080 for the system. We find that the system has a small, but significant, nonzero eccentricity of 0.0136+/- 0.0026. The K2 light curve shows a coherent variation at a period of 3.41315-0.00032+0.00030 days, which is slightly longer than the orbital period, and which we demonstrate comes from the primary star. We interpret this as the rotation period of the primary. We perform a quantitative comparison between the Dartmouth stellar evolution models and the seven systems, including HAT-TR-318-007, that contain M dwarfs with 0.2 M⊙N< M< 0.5 M⊙N, have metallicity measurements, and have masses and radii determined to better than 5% precision. Discrepancies between the predicted and observed masses and radii are found for three of the systems.

  15. Co-expression of G2-EPSPS and glyphosate acetyltransferase GAT genes conferring high tolerance to glyphosate in soybean

    Directory of Open Access Journals (Sweden)

    Bingfu eGuo

    2015-10-01

    Full Text Available Glyphosate is a widely used non-selective herbicide with broad spectrum of weed control around the world. At present, most of the commercial glyphosate tolerant soybeans utilize glyphosate tolerant gene CP4-EPSPS or glyphosate acetyltransferase gene GAT separately. In this study, both glyphosate tolerant gene G2-EPSPS and glyphosate degraded gene GAT were co-transferred into soybean and transgenic plants showed high tolerance to glyphosate. Molecular analysis including PCR, Sothern blot, qRT-PCR and Western blot revealed that target genes have been integrated into genome and expressed effectively at both mRNA and protein levels. Furthermore, the glyphosate tolerance analysis showed that no typical symptom was observed when compared with a glyphosate tolerant line HJ06-698 derived from GR1 transgenic soybean even at four-fold labeled rate of Roundup. Chlorophyll and shikimic acid content analysis of transgenic plant also revealed that these two indexes were not significantly altered after glyphosate application. These results indicated that co-expression of G2-EPSPS and GAT conferred high tolerance to the herbicide glyphosate in soybean. Therefore, combination of tolerant and degraded genes provides a new strategy for developing glyphosate tolerant transgenic crops.

  16. Carnitine acetyltransferase: A new player in skeletal muscle insulin resistance?

    Directory of Open Access Journals (Sweden)

    Sofia Mikkelsen Berg

    2017-03-01

    Full Text Available Carnitine acetyltransferase (CRAT deficiency has previously been shown to result in muscle insulin resistance due to accumulation of long-chain acylcarnitines. However, differences in the acylcarnitine profile and/or changes in gene expression and protein abundance of CRAT in myotubes obtained from obese patients with type 2 diabetes mellitus (T2DM and glucose-tolerant obese and lean controls remain unclear. The objective of the study was to examine whether myotubes from obese patients with T2DM express differences in gene expression and protein abundance of CRAT and in acylcarnitine species pre-cultured under glucose and insulin concentrations similar to those observed in healthy individuals in the over-night fasted, resting state. Primary myotubes obtained from obese persons with or without T2DM and lean controls (n=9 in each group were cultivated and harvested for LC-MS-based profiling of acylcarnitines. The mRNA expression and protein abundance of CRAT were determined by qPCR and Western Blotting, respectively. Our results suggest that the mRNA levels and protein abundance of CRAT were similar between groups. Of the 14 different acylcarnitine species measured by LC-MS, the levels of palmitoylcarnitine (C16 and octadecanoylcarnitine (C18 were slightly reduced in myotubes derived from T2DM patients (p<0.05 compared to glucose-tolerant obese and lean controls. This suggests that the CRAT function is not the major contributor to primary insulin resistance in cultured myotubes obtained from obese T2DM patients.

  17. HDACi: cellular effects, opportunities for restorative dentistry.

    LENUS (Irish Health Repository)

    Duncan, H F

    2011-12-01

    Acetylation of histone and non-histone proteins alters gene expression and induces a host of cellular effects. The acetylation process is homeostatically balanced by two groups of cellular enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). HAT activity relaxes the structure of the human chromatin, rendering it transcriptionally active, thereby increasing gene expression. In contrast, HDAC activity leads to gene silencing. The enzymatic balance can be \\'tipped\\' by histone deacetylase inhibitors (HDACi), leading to an accumulation of acetylated proteins, which subsequently modify cellular processes including stem cell differentiation, cell cycle, apoptosis, gene expression, and angiogenesis. There is a variety of natural and synthetic HDACi available, and their pleiotropic effects have contributed to diverse clinical applications, not only in cancer but also in non-cancer areas, such as chronic inflammatory disease, bone engineering, and neurodegenerative disease. Indeed, it appears that HDACi-modulated effects may differ between \\'normal\\' and transformed cells, particularly with regard to reactive oxygen species accumulation, apoptosis, proliferation, and cell cycle arrest. The potential beneficial effects of HDACi for health, resulting from their ability to regulate global gene expression by epigenetic modification of DNA-associated proteins, also offer potential for application within restorative dentistry, where they may promote dental tissue regeneration following pulpal damage.

  18. Ovarian steroid hormones modulate the expression of progesterone receptors and histone acetylation patterns in uterine leiomyoma cells.

    Science.gov (United States)

    Sant'Anna, Gabriela Dos Santos; Brum, Ilma Simoni; Branchini, Gisele; Pizzolato, Lolita Schneider; Capp, Edison; Corleta, Helena von Eye

    2017-08-01

    Uterine leiomyomas are the most common benign smooth muscle cell tumors in women. Estrogen (E2), progesterone (P4) and environmental factors play important roles in the development of these tumors. New treatments, such as mifepristone, have been proposed. We evaluated the gene expression of total (PRT) and B (PRB) progesterone receptors, and the histone acetyltransferase (HAT) and deacetylase (HDAC) activity after treatment with E2, P4 and mifepristone (RU486) in primary cell cultures from uterine leiomyoma and normal myometrium. Compared to myometrium, uterine leiomyoma cells showed an increase in PRT mRNA expression when treated with E2, and increase in PRB mRNA expression when treated with E2 and P4. Treatment with mifepristone had no significant impact on mRNA expression in these cells. The HDAC activity was higher in uterine leiomyoma compared to myometrial cells after treatment with E2 and E2 + P4 + mifepristone. HAT activity was barely detectable. Our results suggest that ovarian steroid hormones modulate PR, and mifepristone was unable to decrease PRT and PRB mRNA. The higher activity of HDAC leiomyoma cells could be involved in transcriptional repression of genes implicated in normal myometrium cell function, contributing to the maintenance and growth of uterine leiomyoma.

  19. Genome-Wide Identification of Histone Modifiers and Their Expression Patterns during Fruit Abscission in Litchi

    Directory of Open Access Journals (Sweden)

    Jianguo Li

    2017-04-01

    Full Text Available Modifications to histones, including acetylation and methylation processes, play crucial roles in the regulation of gene expression in plant development as well as in stress responses. However, limited information on the enzymes catalyzing histone acetylation and methylation in non-model plants is currently available. In this study, several histone modifier (HM types, including six histone acetyltransferases (HATs, 11 histone deacetylases (HDACs, 48 histone methyltransferases (HMTs, and 22 histone demethylases (HDMs, are identified in litchi (Litchi chinensis Sonn. cv. Feizixiao based on similarities in their sequences to homologs in Arabidopsis (A. thaliana, tomato (Solanum lycopersicum, and rice (Oryza sativa. Phylogenetic analyses reveal that HM enzymes can be grouped into four HAT, two HDAC, two HMT, and two HDM subfamilies, respectively, while further expression profile analyses demonstrate that 17 HMs were significantly altered during fruit abscission in two field treatments. Analyses reveal that these genes exhibit four distinct patterns of expression in response to fruit abscission, while an in vitro assay was used to confirm the HDAC activity of LcHDA2, LcHDA6, and LcSRT2. Our findings are the first in-depth analysis of HMs in the litchi genome, and imply that some are likely to play important roles in fruit abscission in this commercially important plant.

  20. Histone acetylation and CREB binding protein are required for neuronal resistance against ischemic injury.

    Directory of Open Access Journals (Sweden)

    Ferah Yildirim

    Full Text Available Epigenetic transcriptional regulation by histone acetylation depends on the balance between histone acetyltransferase (HAT and deacetylase activities (HDAC. Inhibition of HDAC activity provides neuroprotection, indicating that the outcome of cerebral ischemia depends crucially on the acetylation status of histones. In the present study, we characterized the changes in histone acetylation levels in ischemia models of focal cerebral ischemia and identified cAMP-response element binding protein (CREB-binding protein (CBP as a crucial factor in the susceptibility of neurons to ischemic stress. Both neuron-specific RNA interference and neurons derived from CBP heterozygous knockout mice showed increased damage after oxygen-glucose deprivation (OGD in vitro. Furthermore, we demonstrated that ischemic preconditioning by a short (5 min subthreshold occlusion of the middle cerebral artery (MCA, followed 24 h afterwards by a 30 min occlusion of the MCA, increased histone acetylation levels in vivo. Ischemic preconditioning enhanced CBP recruitment and histone acetylation at the promoter of the neuroprotective gene gelsolin leading to increased gelsolin expression in neurons. Inhibition of CBP's HAT activity attenuated neuronal ischemic preconditioning. Taken together, our findings suggest that the levels of CBP and histone acetylation determine stroke outcome and are crucially associated with the induction of an ischemia-resistant state in neurons.

  1. Microvascular oxygen partial pressure during hyperbaric oxygen in diabetic rat skeletal muscle.

    Science.gov (United States)

    Yamakoshi, Kohei; Yagishita, Kazuyoshi; Tsuchimochi, Hirotsugu; Inagaki, Tadakatsu; Shirai, Mikiyasu; Poole, David C; Kano, Yutaka

    2015-12-15

    Hyperbaric oxygen (HBO) is a major therapeutic treatment for ischemic ulcerations that perforate skin and underlying muscle in diabetic patients. These lesions do not heal effectively, in part, because of the hypoxic microvascular O2 partial pressures (PmvO2 ) resulting from diabetes-induced cardiovascular dysfunction, which alters the dynamic balance between O2 delivery (Q̇o2) and utilization (V̇o2) rates. We tested the hypothesis that HBO in diabetic muscle would exacerbate the hyperoxic PmvO2 dynamics due, in part, to a reduction or slowing of the cardiovascular, sympathetic nervous, and respiratory system responses to acute HBO exposure. Adult male Wistar rats were divided randomly into diabetic (DIA: streptozotocin ip) and healthy (control) groups. A small animal hyperbaric chamber was pressurized with oxygen (100% O2) to 3.0 atmospheres absolute (ATA) at 0.2 ATA/min. Phosphorescence quenching techniques were used to measure PmvO2 in tibialis anterior muscle of anesthetized rats during HBO. Lumbar sympathetic nerve activity (LSNA), heart rate (HR), and respiratory rate (RR) were measured electrophysiologically. During the normobaric hyperoxia and HBO, DIA tibialis anterior PmvO2 increased faster (mean response time, CONT 78 ± 8, DIA 55 ± 8 s, P < 0.05) than CONT. Subsequently, PmvO2 remained elevated at similar levels in CONT and DIA muscles until normobaric normoxic recovery where the DIA PmvO2 retained its hyperoxic level longer than CONT. Sympathetic nervous system and cardiac and respiratory responses to HBO were slower in DIA vs. CONT. Specifically the mean response times for RR (CONT: 6 ± 1 s, DIA: 29 ± 4 s, P < 0.05), HR (CONT: 16 ± 1 s, DIA: 45 ± 5 s, P < 0.05), and LSNA (CONT: 140 ± 16 s, DIA: 247 ± 34 s, P < 0.05) were greater following HBO onset in DIA than CONT. HBO treatment increases tibialis anterior muscle PmvO2 more rapidly and for a longer duration in DIA than CONT, but not to a greater level. Whereas respiratory, cardiovascular

  2. Effects of hyperbaric oxygen on Pseudomonas aeruginosa susceptibility to imipenem and macrophages.

    Science.gov (United States)

    Lima, Flavia Luna; Joazeiro, Paulo Pinto; Lancellotti, Marcelo; de Hollanda, Luciana Maria; de Araújo Lima, Bruna; Linares, Edlaine; Augusto, Ohara; Brocchi, Marcelo; Giorgio, Selma

    2015-01-01

    The seriousness to treat burn wounds infected with Pseudomonas aeruginosa led us to examine whether the effect of the carbapenem antibiotic imipenem is enhanced by hyperbaric oxygen (HBO). The effects of HBO (100% O2, 3 ATA, 5 h) in combination with imipenen on bacterial counts of six isolates of P. aeruginosa and bacterial ultrastructure were investigated. Infected macrophages were exposed to HBO (100% O2, 3 ATA, 90 min) and the production of reactive oxygen species monitored. HBO enhanced the effects of imipenen. HBO increased superoxide anion production by macrophages and likely kills bacteria by oxidative mechanisms. HBO in combination with imipenem can be used to kill P. aeruginosa in vitro and such treatment may be beneficial for the patients with injuries containing the P. aeruginosa.

  3. Resistance to glufosinate is proportional to phosphinothricin acetyltransferase expression and activity in LibertyLink(®) and WideStrike(®) cotton.

    Science.gov (United States)

    Carbonari, Caio A; Latorre, Débora O; Gomes, Giovanna L G C; Velini, Edivaldo D; Owens, Daniel K; Pan, Zhiqiang; Dayan, Franck E

    2016-04-01

    Insertion of the gene encoding phosphinothricin acetyltransferase (PAT) has resulted in cotton plants resistant to the herbicide glufosinate. However, the lower expression and commensurate reduction in PAT activity is a key factor in the low level of injury observed in the WideStrike(®) cotton and relatively high level of resistance observed in LibertyLink(®) cotton. LibertyLink(®) cotton cultivars are engineered for glufosinate resistance by overexpressing the bar gene that encodes phosphinothricin acetyltransferase (PAT), whereas the insect-resistant WideStrike(®) cultivars were obtained using the similar pat gene as a selectable marker. The latter cultivars carry some level of resistance to glufosinate which enticed certain farmers to select this herbicide for weed control with WideStrike(®) cotton. The potency of glufosinate on conventional FM 993, insect-resistant FM 975WS, and glufosinate-resistant IMACD 6001LL cotton cultivars was evaluated and contrasted to the relative levels of PAT expression and activity. Conventional cotton was sensitive to glufosinate. The single copy of the pat gene present in the insect-resistant cultivar resulted in very low RNA expression of the gene and undetectable PAT activity in in vitro assays. Nonetheless, the presence of this gene provided a good level of resistance to glufosinate in terms of visual injury and effect on photosynthetic electron transport. The injury is proportional to the amount of ammonia accumulation. The strong promoter associated with bar expression in the glufosinate-resistant cultivar led to high RNA expression levels and PAT activity which protected this cultivar from glufosinate injury. While the insect-resistant cultivar demonstrated a good level of resistance to glufosinate, its safety margin is lower than that of the glufosinate-resistant cultivar. Therefore, farmers should be extremely careful in using glufosinate on cultivars not expressly designed and commercialized as resistant to this

  4. Structures and functions of insect arylalkylamine N-acetyltransferase (iaaNAT; a key enzyme for physiological and behavioral switch in arthropods

    Directory of Open Access Journals (Sweden)

    Susumu eHiragaki

    2015-04-01

    Full Text Available The evolution of N-acetyltransfeases (NATs seems complex. Vertebrate arylalkylamine N-acetyltransferase (aaNAT has been extensively studied since it Leads to the synthesis of melatonin, a multifunctional neurohormone prevalent in photoreceptor cells, and is known as as a chemical token of the night. Melatonin also serves as a scavenger for reactive oxygen species. This is also true with invertebrates. NAT therefore has distinct functional implications in circadian function, as timezymes (aaNAT, and also xenobiotic reactions (arylamine NAT or simply NAT. NATs belong to a broader enzyme group, the GCN5-related N-acetyltransferase superfamily. Due to low sequence homology and a seemingly fast rate of structural differentiation, the nomenclature for NATs can be confusing. The advent of bioinformatics, however, has helped to classify this group of enzymes; vertebrates have two distinct subgroups, the timezyme type and the xenobiotic type, which has a wider substrate range including imidazolamine, pharmacological drugs, environmental toxicants and even histone. Insect aaNAT (iaaNAT form their own clade in the phylogeny, distinct from vertebrate aaNATs. Arthropods are unique, since the phylum has exoskeleton in which quinones derived from N-acetylated monoamines function in coupling chitin and arthropodins. Monoamine oxidase (MAO activity is limited in insects, but NAT-mediated degradation prevails. However, unexpectedly iaaNAT occurs not only among arthropods but also among basal deuterostomia, and is therefore more apomorphic. Our analyses illustrate that iaaNATs has unique physiological roles but at the same time it plays a role in a timezyme function, at least in photoperiodism. Photoperiodism has been considered as a function of circadian system but the detailed molecular mechanism is not well understood. We propose a molecular hypothesis for photoperiodism in Antheraea pernyi based on the transcription regulation of NAT interlocked by the

  5. "It's your badge of inclusion": the Red Hat Society as a gendered subculture of aging.

    Science.gov (United States)

    Barrett, Anne E; Pai, Manacy; Redmond, Rebecca

    2012-12-01

    Although studies document the health-enhancing effects of social engagement, they reveal little about the underlying mechanisms operating within specific organizational contexts. Limited attention is given to the role of inequality--particularly age and gender--in shaping either the organizations to which we belong or their consequences for our well-being. We address this issue by examining the Red Hat Society, a social organization for middle-aged and older women. Interviews with members (n=52) illustrate how age and gender inequality interact to shape the organization, which can be viewed as a gendered subculture of aging. Drawing on this framework, we discuss four processes through which participation generates benefits for older women involved in age- and gender-segregated organizations: enhancing social networks, countering invisibility, creating positive frames for aging experiences, and promoting youthful identities. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Hyperbaric oxygenation therapy for crush injuries reduces the risk of complications: research report.

    Science.gov (United States)

    Yamada, Noriaki; Toyoda, Izumi; Doi, Tomoaki; Kumada, Keisuke; Kato, Hisaaki; Yoshida, Shozo; Shirai, Kunihiro; Kanda, Norihide; Ogura, Shinji

    2014-01-01

    Hyperbaric oxygen (HBO2) therapy has been adopted for crush injuries, but there are few studies supporting its use. We therefore investigated the effects of HBO2 on management of patients with complicated crush injuries. This historic cohort study included patients with crush injuries and open fractures with severities greater than or equal to Gustilo class IIIA. We divided the patients into two groups: Control and HBO2. The control group received conventional treatment, while the HBO2 group received conventional treatment plus HBO2. We compared the groups with respect to the incidence of infection, need for additional surgery, and length of intensive care unit (ICU) and hospital stays. There were 16 patients in the HBO2 group and 13 in the control group. There were no patients with infections in the HBO2 group, whereas in the control group six patients had infections and five needed another drainage procedure. These incidences were significantly lower in the HBO2 group (p = 0.003 and 0.013). However, the durations of ICU and hospital stays were similar across the two groups. HBO2 is effective in the management of crush injuries from the viewpoint of reducing complications and reoperations. These observations should be verified in additional studies with larger sample sizes because the patient number is limited.

  7. Groundwater evolution beneath Hat Yai, a rapidly developing city in Thailand

    Science.gov (United States)

    Lawrence, A. R.; Gooddy, D. C.; Kanatharana, P.; Meesilp, W.; Ramnarong, V.

    2000-09-01

    Many cities and towns in South and Southeast Asia are unsewered, and urban wastewaters are often discharged either directly to the ground or to surface-water canals and channels. This practice can result in widespread contamination of the shallow groundwater. In Hat Yai, southern Thailand, seepage of urban wastewaters has produced substantial deterioration in the quality of the shallow groundwater directly beneath the city. For this reason, the majority of the potable water supply is obtained from groundwater in deeper semi-confined aquifers 30-50 m below the surface. However, downward leakage of shallow groundwater from beneath the city is a significant component of recharge to the deeper aquifer, which has long-term implications for water quality. Results from cored boreholes and shallow nested piezometers are presented. The combination of high organic content of the urban recharge and the shallow depth to the water table has produced strongly reducing conditions in the upper layer and the mobilisation of arsenic. A simple analytical model shows that time scales for downward leakage, from the surface through the upper aquitard to the semi-confined aquifer, are of the order of several decades. Résumé. De nombreuses villes du sud et du sud-est de l'Asie ne possèdent pas de réseaux d'égouts et les eaux usées domestiques s'écoulent souvent directement sur le sol ou dans des canaux et des cours d'eau de surface. Ces pratiques peuvent provoquer une contamination dispersée de la nappe phréatique. A Hat Yai (sud de la Thaïlande), les infiltrations d'eaux usées domestiques sont responsables d'une détérioration notable de la qualité de la nappe phréatique directement sous la ville. Pour cette raison, la majorité de l'eau potable est prélevée dans des aquifères semi-captifs plus profonds, situés entre 30 et 50 m sous la surface. Cependant, une drainance à partir de la nappe phréatique sous la ville constitue une composante significative de la recharge

  8. Defining the extreme substrate specificity of Euonymus alatus diacylglycerol acetyltransferase, an unusual membrane-bound O-acyltransferase

    Science.gov (United States)

    Bansal, Sunil; Durrett, Timothy P.

    2016-01-01

    Euonymus alatus diacylglycerol acetyltransferase (EaDAcT) synthesizes the unusually structured 3-acetyl-1,2-diacylglycerols (acetyl-TAG) found in the seeds of a few plant species. A member of the membrane-bound O-acyltransferase (MBOAT) family, EaDAcT transfers the acetyl group from acetyl-CoA to sn-1,2-diacylglycerol (DAG) to produce acetyl-TAG. In vitro assays demonstrated that the enzyme is also able to utilize butyryl-CoA and hexanoyl-CoA as acyl donors, though with much less efficiency compared with acetyl-CoA. Acyl-CoAs longer than eight carbons were not used by EaDAcT. This extreme substrate specificity of EaDAcT distinguishes it from all other MBOATs which typically catalyze the transfer of much longer acyl groups. In vitro selectivity experiments revealed that EaDAcT preferentially acetylated DAG molecules containing more double bonds over those with less. However, the enzyme was also able to acetylate saturated DAG containing medium chain fatty acids, albeit with less efficiency. Interestingly, EaDAcT could only acetylate the free hydroxyl group of sn-1,2-DAG but not the available hydroxyl groups in sn-1,3-DAG or in monoacylglycerols (MAG). Consistent with its similarity to the jojoba wax synthase, EaDAcT could acetylate fatty alcohols in vitro to produce alkyl acetates. Likewise, when coexpressed in yeast with a fatty acyl-CoA reductase capable of producing fatty alcohols, EaDAcT synthesized alkyl acetates although the efficiency of production was low. This improved understanding of EaDAcT specificity confirms that the enzyme preferentially utilizes acetyl-CoA to acetylate sn-1,2-DAGs and will be helpful in engineering the production of acetyl-TAG with improved functionality in transgenic plants. PMID:27688773

  9. Inference of Functionally-Relevant N-acetyltransferase Residues Based on Statistical Correlations.

    Directory of Open Access Journals (Sweden)

    Andrew F Neuwald

    2016-12-01

    Full Text Available Over evolutionary time, members of a superfamily of homologous proteins sharing a common structural core diverge into subgroups filling various functional niches. At the sequence level, such divergence appears as correlations that arise from residue patterns distinct to each subgroup. Such a superfamily may be viewed as a population of sequences corresponding to a complex, high-dimensional probability distribution. Here we model this distribution as hierarchical interrelated hidden Markov models (hiHMMs, which describe these sequence correlations implicitly. By characterizing such correlations one may hope to obtain information regarding functionally-relevant properties that have thus far evaded detection. To do so, we infer a hiHMM distribution from sequence data using Bayes' theorem and Markov chain Monte Carlo (MCMC sampling, which is widely recognized as the most effective approach for characterizing a complex, high dimensional distribution. Other routines then map correlated residue patterns to available structures with a view to hypothesis generation. When applied to N-acetyltransferases, this reveals sequence and structural features indicative of functionally important, yet generally unknown biochemical properties. Even for sets of proteins for which nothing is known beyond unannotated sequences and structures, this can lead to helpful insights. We describe, for example, a putative coenzyme-A-induced-fit substrate binding mechanism mediated by arginine residue switching between salt bridge and π-π stacking interactions. A suite of programs implementing this approach is available (psed.igs.umaryland.edu.

  10. Inference of Functionally-Relevant N-acetyltransferase Residues Based on Statistical Correlations.

    Science.gov (United States)

    Neuwald, Andrew F; Altschul, Stephen F

    2016-12-01

    Over evolutionary time, members of a superfamily of homologous proteins sharing a common structural core diverge into subgroups filling various functional niches. At the sequence level, such divergence appears as correlations that arise from residue patterns distinct to each subgroup. Such a superfamily may be viewed as a population of sequences corresponding to a complex, high-dimensional probability distribution. Here we model this distribution as hierarchical interrelated hidden Markov models (hiHMMs), which describe these sequence correlations implicitly. By characterizing such correlations one may hope to obtain information regarding functionally-relevant properties that have thus far evaded detection. To do so, we infer a hiHMM distribution from sequence data using Bayes' theorem and Markov chain Monte Carlo (MCMC) sampling, which is widely recognized as the most effective approach for characterizing a complex, high dimensional distribution. Other routines then map correlated residue patterns to available structures with a view to hypothesis generation. When applied to N-acetyltransferases, this reveals sequence and structural features indicative of functionally important, yet generally unknown biochemical properties. Even for sets of proteins for which nothing is known beyond unannotated sequences and structures, this can lead to helpful insights. We describe, for example, a putative coenzyme-A-induced-fit substrate binding mechanism mediated by arginine residue switching between salt bridge and π-π stacking interactions. A suite of programs implementing this approach is available (psed.igs.umaryland.edu).

  11. Electronic and photophysical properties of 2-(2′-hydroxyphenyl)benzoxazole and its derivatives enhancing in the excited-state intramolecular proton transfer processes: A TD-DFT study on substitution effect

    Energy Technology Data Exchange (ETDEWEB)

    Daengngern, Rathawat; Kungwan, Nawee, E-mail: naweekung@gmail.com

    2015-11-15

    The effect of electron donating and withdrawing substituents on the enol absorption and keto emission spectra of 2-(2′-hydroxyphenyl)benzoxazole (HBO) and its derivatives has been systematically investigated by means of density functional theory (DFT) and time-dependent DFT (TD-DFT) methods. The enol absorption spectra of HBO were simulated by using five different DFTs with various exchange-correlation functions to validate a suitable functional prior to being further used as a method of choice to study the effect of substituents on the spectral characteristics of HBO derivatives. The popular B3LYP (Becke, three-parameter, Lee–Yang–Parr) exchange-correlation functional is found to provide the best desirable result in predicting the absorption spectrum close to experimental data. In the ground state, enol forms of HBO and its derivatives are more stable than those of keto forms, while in the first lowest excited state, keto forms are found to be more stable than their enol forms. Overall, simulated absorption and emission spectra of HBO and its derivatives from TD-B3LYP calculations are in good agreement with the experimental data. For enol, absorption maxima of HBO derivatives having electron-withdrawing groups are red-shift corresponding to their lower HOMO–LUMO energy gaps compared to that of HBO. For keto emission, HBO having electron donating groups (m-MeHBO and MHBO) and withdrawing group (CNHBO) at 4′-position on the phenol fragment as well as electron donating groups (HBOMe and HBOM) at 6-position on the benzoxazole fragment make the position of keto emission peak shift to shorter wavelength (blue-shift). However, HBO derivatives with electron withdrawing groups (HBOF, HBOCl, HBOA and HBOE) at 6-position give redshifted emission compared to the parent compound (HBO). The type of substituent on both 4′- and 6-positions certainly has a pronounced effect on the absorption and emission spectra of HBO derivatives. - Highlights: • Simulated spectra

  12. Electronic and photophysical properties of 2-(2′-hydroxyphenyl)benzoxazole and its derivatives enhancing in the excited-state intramolecular proton transfer processes: A TD-DFT study on substitution effect

    International Nuclear Information System (INIS)

    Daengngern, Rathawat; Kungwan, Nawee

    2015-01-01

    The effect of electron donating and withdrawing substituents on the enol absorption and keto emission spectra of 2-(2′-hydroxyphenyl)benzoxazole (HBO) and its derivatives has been systematically investigated by means of density functional theory (DFT) and time-dependent DFT (TD-DFT) methods. The enol absorption spectra of HBO were simulated by using five different DFTs with various exchange-correlation functions to validate a suitable functional prior to being further used as a method of choice to study the effect of substituents on the spectral characteristics of HBO derivatives. The popular B3LYP (Becke, three-parameter, Lee–Yang–Parr) exchange-correlation functional is found to provide the best desirable result in predicting the absorption spectrum close to experimental data. In the ground state, enol forms of HBO and its derivatives are more stable than those of keto forms, while in the first lowest excited state, keto forms are found to be more stable than their enol forms. Overall, simulated absorption and emission spectra of HBO and its derivatives from TD-B3LYP calculations are in good agreement with the experimental data. For enol, absorption maxima of HBO derivatives having electron-withdrawing groups are red-shift corresponding to their lower HOMO–LUMO energy gaps compared to that of HBO. For keto emission, HBO having electron donating groups (m-MeHBO and MHBO) and withdrawing group (CNHBO) at 4′-position on the phenol fragment as well as electron donating groups (HBOMe and HBOM) at 6-position on the benzoxazole fragment make the position of keto emission peak shift to shorter wavelength (blue-shift). However, HBO derivatives with electron withdrawing groups (HBOF, HBOCl, HBOA and HBOE) at 6-position give redshifted emission compared to the parent compound (HBO). The type of substituent on both 4′- and 6-positions certainly has a pronounced effect on the absorption and emission spectra of HBO derivatives. - Highlights: • Simulated spectra

  13. Identification and characterization of a new bocavirus species in gorillas.

    Directory of Open Access Journals (Sweden)

    Amit Kapoor

    2010-07-01

    Full Text Available A novel parvovirus, provisionally named Gorilla Bocavirus species 1 (GBoV1, was identified in four stool samples from Western gorillas (Gorilla gorilla with acute enteritis. The complete genomic sequence of the new parvovirus revealed three open reading frames (ORFs with an organization similar to that of known bocaviruses. Phylogenetic analysis using complete capsid and non structural (NS gene sequence suggested that the new parvovirus is most closely related to human bocaviruses (HBoV. However, the NS ORF is more similar in length to the NS ORF found in canine minute virus and bovine parvovirus than in HBoV. Comparative genetic analysis using GBoV and HBoV genomes enabled characterization of unique splice donor and acceptor sites that appear to be highly conserved among all four HBoV species, and provided evidence for expression of two different NS proteins in all primate bocaviruses. GBoV is the first non-human primate bocavirus identified and provides new insights into the genetic diversity and evolution of this highly prevalent and recently discovered group of parvoviruses.

  14. Investigation of the effect and mechanism of hyperbaric oxygenation therapy on neonatal hypoxic-ischemic encephalopathy with SPECT

    International Nuclear Information System (INIS)

    Jia Shaowei; Yi Zhi; Liao Jianxiang

    2001-01-01

    Objective: To evaluate the effect of HBO on neonatal hypoxic-ischemic encephalopathy with SPECT, and to explore the mechanisms. Methods: The research subjects were totally 34 newborn babies, including 3 normal neonates. The group treated with HBO included 20 babies with HIE, and the control group contained 11 HIE babies. All babies in both groups received SPECT exams before and after the treatments. Results: SPECT before treatment showed 46 foci of low perfusion and functional defect or insufficiencies in 31 HIE babies. SPECT after 1-2 period of treatments of HBO therapy in HIE babies showed disappeared or reduced low perfusion and functional defect or insufficiency in the brains. The HIE babies in the control group showed improvement with less degree than HBO treated babies. There were significant differences (P<0.01) between two groups. Conclusion: The effect of HBO on HIE babies were prominent. The treatment can improve the hypoxic status of brain cell through increase the regional cerebral blood flow perfusion and oxygen content of the brain tissue, then provoked the brain cells activities, and at last, enhance the repair of the injured brain cells

  15. Tarih Algısı Bağlamında Postmodern Bir Anlatı: İstanbul Hatırası A Postmodern Narration in the Context of History Perception: İstanbul Hatırası

    Directory of Open Access Journals (Sweden)

    Mustafa AYDEMİR

    2012-09-01

    Full Text Available Detective novel, formed around an intelligently planned murder and a detective who tries to solve it and find the murderer, shows a significant improvement with the influence of Postmodernism, which rose in the second half of 20th Century. That improvement first shows its face in translation, then writing in Turkish Literature. The history of detective novel, which began to take its place inliterary history due to the emergence of crime and along withurbanization, is as old as the concept of crime history. Having aparticular history, it can be claimed that it prepared the ground for theemergence of novel. However, two major war, which happened in the20th century, has led to a rapid development of the detective novel, thebest way to tell the story of the crimes.Ahmet Ümit’s novel İstanbul Hatırası is important as it shows thechange of detective novel in Turkish novel. A real – up to date and anunreal – historical, two different engaging fictions are being narrated inthat detective novel. Beginning with the murder, a journey to thehistorical sites of Istanbul is made. In addition, the importances ofthese sites, which are close to be destroyed, are pointed out.In this study, after mentioning how detective novel emerged inWest and Turkish Literature and its historic development, Ahmet Ümit’sİstanbul Hatırası has been analyzed and postmodern features in thisnovel has been emphasized. With this method, postmoderncharacteristics of the novel has been taken care in terms of plot, time,place, characters and the classical elements of the novel has beenevaluated with a postmodernist approach. Zekice plânlanmış bir cinayet ve onu çözmeye, katili bulmaya çalışan bir dedektif etrafında şekillenen polisiye roman, 20. yüzyılın ikinci yarısında ortaya çıkan postmodernizmin de etkisiyle önemli bir gelişme gösterir. Bu gelişme, Türk edebiyatında önce çeviri, sonra da telif yoluyla kendini gösterir. Suçun ortaya

  16. Human neural stem cells over-expressing choline acetyltransferase restore cognition in rat model of cognitive dysfunction.

    Science.gov (United States)

    Park, Dongsun; Lee, Hong Jun; Joo, Seong Soo; Bae, Dae-Kwon; Yang, Goeun; Yang, Yun-Hui; Lim, Inja; Matsuo, Akinori; Tooyama, Ikuo; Kim, Yun-Bae; Kim, Seung U

    2012-04-01

    A human neural stem cell (NSC) line over-expressing human choline acetyltransferase (ChAT) gene was generated and these F3.ChAT NSCs were transplanted into the brain of rat Alzheimer disease (AD) model which was induced by application of ethylcholine mustard aziridinium ion (AF64A) that specifically denatures cholinergic nerves and thereby leads to memory deficit as a salient feature of AD. Transplantation of F3.ChAT human NSCs fully recovered the learning and memory function of AF64A animals, and induced elevated levels of acetylcholine (ACh) in cerebrospinal fluid (CSF). Transplanted F3.ChAT human NSCs were found to migrate to various brain regions including cerebral cortex, hippocampus, striatum and septum, and differentiated into neurons and astrocytes. The present study demonstrates that brain transplantation of human NSCs over-expressing ChAT ameliorates complex learning and memory deficits in AF64A-cholinotoxin-induced AD rat model. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Sulfonamide-Based Inhibitors of Aminoglycoside Acetyltransferase Eis Abolish Resistance to Kanamycin in Mycobacterium tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Garzan, Atefeh; Willby, Melisa J.; Green, Keith D.; Gajadeera, Chathurada S.; Hou, Caixia; Tsodikov, Oleg V.; Posey, James E.; Garneau-Tsodikova, Sylvie

    2016-12-08

    A two-drug combination therapy where one drug targets an offending cell and the other targets a resistance mechanism to the first drug is a time-tested, yet underexploited approach to combat or prevent drug resistance. By high-throughput screening, we identified a sulfonamide scaffold that served as a pharmacophore to generate inhibitors of Mycobacterium tuberculosis acetyltransferase Eis, whose upregulation causes resistance to the aminoglycoside (AG) antibiotic kanamycin A (KAN) in Mycobacterium tuberculosis. Rational systematic derivatization of this scaffold to maximize Eis inhibition and abolish the Eis-mediated KAN resistance of M. tuberculosis yielded several highly potent agents. A crystal structure of Eis in complex with one of the most potent inhibitors revealed that the inhibitor bound Eis in the AG-binding pocket held by a conformationally malleable region of Eis (residues 28–37) bearing key hydrophobic residues. These Eis inhibitors are promising leads for preclinical development of innovative AG combination therapies against resistant TB.

  18. ORF Alignment: NC_002945 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available ] ... pdb|1M4I|B Chain B, Aminoglycoside ... 2'-N-Acetyltransferase From Mycobacterium ... Tuberculosis...ain A, Aminoglycoside ... 2'-N-Acetyltransferase From Mycobacterium ... Tuberculosis-Complex W...se From Mycobacterium ... Tuberculosis-Complex With Coenzyme A And Ribostamycin ... pdb|1M4G|A... Chain A, Aminoglycoside ... 2'-N-Acetyltransferase From Mycobacterium ... Tuberculosis... ... 2'-N-Acetyltransferase From Mycobacterium ... Tuberculosis-Complex With Coenzyme A And Tob

  19. ORF Alignment: NC_000962 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available ] ... pdb|1M4I|B Chain B, Aminoglycoside ... 2'-N-Acetyltransferase From Mycobacterium ... Tuberculosis...ain A, Aminoglycoside ... 2'-N-Acetyltransferase From Mycobacterium ... Tuberculosis-Complex W...se From Mycobacterium ... Tuberculosis-Complex With Coenzyme A And Ribostamycin ... pdb|1M4G|A... Chain A, Aminoglycoside ... 2'-N-Acetyltransferase From Mycobacterium ... Tuberculosis... ... 2'-N-Acetyltransferase From Mycobacterium ... Tuberculosis-Complex With Coenzyme A And Tob

  20. ORF Alignment: NC_002755 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available ] ... pdb|1M4I|B Chain B, Aminoglycoside ... 2'-N-Acetyltransferase From Mycobacterium ... Tuberculosis...ain A, Aminoglycoside ... 2'-N-Acetyltransferase From Mycobacterium ... Tuberculosis-Complex W...se From Mycobacterium ... Tuberculosis-Complex With Coenzyme A And Ribostamycin ... pdb|1M4G|A... Chain A, Aminoglycoside ... 2'-N-Acetyltransferase From Mycobacterium ... Tuberculosis... ... 2'-N-Acetyltransferase From Mycobacterium ... Tuberculosis-Complex With Coenzyme A And Tob

  1. Alba from Thermoplasma volcanium belongs to α-NAT's: An insight into the structural aspects of Tv Alba and its acetylation by Tv Ard1.

    Science.gov (United States)

    Ma, Chao; Pathak, Chinar; Lee, Sang Jae; Lee, Ki-Young; Jang, Sun-Bok; Nam, Minjoo; Im, Hookang; Yoon, Hye-Jin; Lee, Bong-Jin

    2016-01-15

    The Alba superfamily proteins have been regarded as a conserved group of proteins in archaea and eukarya, which have shown to be important in nucleic acid binding, chromatic organization and gene regulation. These proteins often belong to the N-acetyltransferase (NAT) category (N(α)-acetyltransferases or N(ε)-acetyltransferases) and undergo post-translational modifications. Here, we report the crystal structure of Alba from Thermoplasma volcanium (Tv Alba) at 2.4 Å resolution. The acetylation of Tv Alba was monitored and the N-terminal of Tv Alba has been shown to interact with acetyl coenzyme A (Ac-CoA). The chemical shift perturbation experiments of Tv Alba were performed in the presence of Ac-CoA and/or Tv Ard1, another T. volcanium protein that treats Tv Alba as a substrate. To examine the DNA binding capabilities of Tv Alba alone and in the presence of Ac-CoA and/or Tv Ard1, EMSA experiments were carried out. It is shown that although Tv Alba binds to Ac-CoA, the acetylation of Tv Alba is not related with its binding to dsDNA, and the involvement of the N-terminus in Ac-CoA binding demonstrates that Tv Alba belongs to the N(α)-acetyltransferase family. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. daf-31 encodes the catalytic subunit of N alpha-acetyltransferase that regulates Caenorhabditis elegans development, metabolism and adult lifespan.

    Science.gov (United States)

    Chen, Di; Zhang, Jiuli; Minnerly, Justin; Kaul, Tiffany; Riddle, Donald L; Jia, Kailiang

    2014-10-01

    The Caenorhabditis elegans dauer larva is a facultative state of diapause. Mutations affecting dauer signal transduction and morphogenesis have been reported. Of these, most that result in constitutive formation of dauer larvae are temperature-sensitive (ts). The daf-31 mutant was isolated in genetic screens looking for novel and underrepresented classes of mutants that form dauer and dauer-like larvae non-conditionally. Dauer-like larvae are arrested in development and have some, but not all, of the normal dauer characteristics. We show here that daf-31 mutants form dauer-like larvae under starvation conditions but are sensitive to SDS treatment. Moreover, metabolism is shifted to fat accumulation in daf-31 mutants. We cloned the daf-31 gene and it encodes an ortholog of the arrest-defective-1 protein (ARD1) that is the catalytic subunit of the major N alpha-acetyltransferase (NatA). A daf-31 promoter::GFP reporter gene indicates daf-31 is expressed in multiple tissues including neurons, pharynx, intestine and hypodermal cells. Interestingly, overexpression of daf-31 enhances the longevity phenotype of daf-2 mutants, which is dependent on the forkhead transcription factor (FOXO) DAF-16. We demonstrate that overexpression of daf-31 stimulates the transcriptional activity of DAF-16 without influencing its subcellular localization. These data reveal an essential role of NatA in controlling C. elegans life history and also a novel interaction between ARD1 and FOXO transcription factors, which may contribute to understanding the function of ARD1 in mammals.

  3. Indonesia Cohort of IO HAT Study to Evaluate Diabetes Management, Control, and Complications in Retrospective and Prospective Periods Among Insulin-Treated Patients with Type 1 and Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Achmad Rudijanto

    2018-04-01

    Full Text Available Background: hypoglycemia is a major adverse event of insulin therapy for diabetes mellitus patients. The study was conducted to evaluate the incidence of hypoglycemia among insulin treated patients with type 1 diabetes mellitus (T1DM or type 2 diabetes mellitus (T2DM in the Indonesian cohort. Methods: this Indonesian cohort study consisted of retrospective and prospective evaluation of hypoglycemic episodes, using International Operations Hypoglycemia Assessment Tool (IO HAT in 374 patients with diabetes (T1DM; n=17 or T2DM; n=357. The patients of ≥18 years of age and treated with insulin for >12 months were selected for this study (ClinicalTrials.gov number: NCT02306681. Results: a total of 374 patients were enrolled in this study and completed SAQ1. All patients with T1DM (17 [100%], and 347 (97.2% patients with T2DM completed SAQ2. Almost all the patients in the 4-week prospective period reported at least one hypoglycemic event (T1DM 100%, T2DM 99.4% and the incidence rate of any hypoglycemia was 67.5 events per patient-year (PPY and 25.7 events PPY for T1DM and T2DM patients, respectively. Among patients with T1DM and T2DM, 5.9% and 36.4%, respectively, did not know what hypoglycemia was at baseline, also high proportion of patients had impaired hypoglycemic awareness in the study (82.4% and 62.7%, respectively. Conclusion: overall, high proportion of patients reported hypoglycemic events in the prospective period indicating under reporting during the retrospective period due to recall bias. Therefore, there is a need for patient education program to improve the awareness of hypoglycemia in diabetes patient in Indonesia.

  4. HYPERBARIC OXYGENT HERAPY AND CANCER - A REVIEW.

    Directory of Open Access Journals (Sweden)

    I. Moen

    2015-01-01

    Full Text Available Hypoxia is a critical hallmark of solid tumors and involves enhanced cell survival, angiogenesis, glycolytic metabolism, andmetastasis. Hyperbaric oxygen (HBO treatment has for centuries been used to improve or cure disorders involving hypoxia and ischemia, by enhancing the amount of dissolved oxygen in the plasma and thereby increasing О2 delivery to the tissue. Studies on HBO and cancer have up to recently focused on whether enhanced oxygen acts as a cancer promoter or not. As oxygen is believed to be required for all the major processes of wound healing, one feared that the effects of HBO would be applicable to cancer tissue as well and promote cancer growth. Furthermore, one also feared that exposing patients who had been treated for cancer, to HBO, would lead to recurrence. Nevertheless, two systematic reviews on HBO and cancer have concluded that the use of HBO in patients with malignancies is considered safe. To supplement the previous reviews, we have summarized the work performed on HBO and cancer in the period 2004–2012. Based on the present as well as previous reviews, there is no evidence indicating that HBO neither acts as a stimulator of tumor growth nor as an enhancer of recurrence. On the other hand, there is evidence that implies that HBO might have tumor-inhibitory effects in certain cancer subtypes, and we thus strongly believe that we need to expand our knowledge on the effect and the mechanisms behind tumor oxygenation.

  5. The effect of increased yeast alcohol acetyltransferase and esterase activity on the flavour profiles of wine and distillates.

    Science.gov (United States)

    Lilly, Mariska; Bauer, Florian F; Lambrechts, Marius G; Swiegers, Jan H; Cozzolino, Daniel; Pretorius, Isak S

    2006-07-15

    The fruity odours of wine are largely derived from the synthesis of esters and higher alcohols during yeast fermentation. The ATF1- and ATF2-encoded alcohol acetyltransferases of S. cerevisiae are responsible for the synthesis of ethyl acetate and isoamyl acetate esters, while the EHT1-encoded ethanol hexanoyl transferase is responsible for synthesizing ethyl caproate. However, esters such as these might be degraded by the IAH1-encoded esterase. The objectives of this study were: (a) to overexpress the genes encoding ester-synthesizing and ester-degrading enzymes in wine yeast; (b) to prepare Colombard table wines and base wines for distillation using these modified strains; and (c) to analyse and compare the ester concentrations and aroma profiles of these wines and distillates. The overexpression of ATF1 significantly increased the concentrations of ethyl acetate, isoamyl acetate, 2-phenylethyl acetate and ethyl caproate, while the overexpression of ATF2 affected the concentrations of ethyl acetate and isoamyl acetate to a lesser degree. The overexpression of IAH1 resulted in a significant decrease in ethyl acetate, isoamyl acetate, hexyl acetate and 2-phenylethyl acetate. The overexpression of EHT1 resulted in a marked increase in ethyl caproate, ethyl caprylate and ethyl caprate. The flavour profile of the wines and distillates prepared using the modified strains were also significantly altered as indicated by formal sensory analysis. This study offers prospects for the development of wine yeast starter strains with optimized ester-producing capability that could assist winemakers in their effort to consistently produce wine and distillates such as brandy to definable flavour specifications and styles.

  6. The HAT TRICK programme for improving physical activity, healthy eating and connectedness among overweight, inactive men: study protocol of a pragmatic feasibility trial.

    Science.gov (United States)

    Caperchione, Cristina M; Bottorff, Joan L; Oliffe, John L; Johnson, Steven T; Hunt, Kate; Sharp, Paul; Fitzpatrick, Kayla M; Price, Ryley; Goldenberg, S Larry

    2017-09-06

    Physical activity, healthy eating and maintaining a healthy weight are associated with reduced risk of cardiovascular disease, type 2 diabetes and cancer and with improved mental health. Despite these benefits, many men do not meet recommended physical activity guidelines and have poor eating behaviours. Many health promotion programmes hold little appeal to men and consequently fail to influence men's health practices. HAT TRICK was designed as a 12-week face-to-face, gender-sensitised intervention for overweight and inactive men focusing on physical activity, healthy eating and social connectedness and was delivered in collaboration with a major junior Canadian ice hockey team (age range 16-20 years). The programme was implemented and evaluated to assess its feasibility. This article describes the intervention design and study protocol of HAT TRICK. HAT TRICK participants (n=60) were men age 35 years, residing in the Okanagan Region of British Columbia, who accumulate 150 min of moderate to vigorous physical activity a week, with a body mass index of >25 kg/m 2 and a pant waist size of >38'. Each 90 min weekly session included targeted health education and theory-guided behavioural change techniques, as well as a progressive (ie, an increase in duration and intensity) group physical activity component. Outcome measures were collected at baseline, 12 weeks and 9 months and included the following: objectively measured anthropometrics, blood pressure, heart rate, physical activity and sedentary behaviour, as well as self-reported physical activity, sedentary behaviour, diet, smoking, alcohol consumption, sleep habits, risk of depression, health-related quality of life and social connectedness. Programme feasibility data (eg, recruitment, satisfaction, adherence, content delivery) were assessed at 12 weeks via interviews and self-report. Ethical approval was obtained from the University of British Columbia Okanagan Behavioural Research Ethics Board (reference no H

  7. TAF10 and TAF10b partially redundant roles during Drosophila melanogaster morphogenesis.

    Science.gov (United States)

    Pahi, Z; Borsos, B N; Vedelek, B; Shidlovskii, Y V; Georgieva, S G; Boros, I M; Pankotai, T

    2017-01-01

    Transcription of eukaryotic genes requires the cooperative action of the RNA polymerase complex, the general transcription factors (TFIIB, TFIID, TFIIE, TFIIF and TFIIH) and chromatin modifiers. The TFIID complex contributes to transcriptional activation by several mechanisms and has a subunit with associated histone acetyltransferase (HAT) activity. The histone modifier SAGA complex has both HAT and deubiquitylase (DUB) activities. TFIID and SAGA share several TBP-associated factors (TAFs), but not their HAT subunit. Recently, several duplicated TAF proteins have been identified in higher eukaryotes, but their functional diversity has been so far poorly characterized. Here, we report the functional similarities and differences of TAF10 and TAF10b, the two TAF10 orthologs of Drosophila melanogaster. Results from in silico modeling suggest that dTAF10 and dTAF10b have similar secondary structures characterized by the presence of a histone-fold domain. Additionally, dTAF10 and dTAF10b share interaction partners and show similar expression patterns in neuronal tissues. Nonetheless, dTAF10 and dTAF10b seem to have partly distinct functions. To investigate their roles, we generated dTaf10-dTaf10b double-mutants and rescued the mutant flies with transgenes, which allowed the translation of either dTAF10 or dTAF10b protein. We found that the loss of dTAF10b resulted in pupal lethality, while animals lacking dTAF10 were able to form puparium. dTaf10 mutant adults showed distorted eye morphology. During DNA repair, dTAF10 and dTAF10b act redundantly, suggesting that these proteins have distinct but partially overlapping functions.

  8. The Effectiveness of Adjuvant Hyperbaric Oxygen Therapy in Adults who Underwent Hypospadias Surgery

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    Onder Kara

    2017-01-01

    Full Text Available Aim: To evaluate the role of hyperbaric oxygen therapy (HBO2T with buccal mucosal tube urethroplasty in adult patients with hypospadias. Material and Method: Sixteen adult patients with hypospadias were included in our study. Patients with a short urethra and penile curvature were treated in two stages (orthoplasty buccal mucosal tube urethroplasty. Buccal mucosa was taken and prepared for tube urethroplasty around a 16 French (Fr nelaton catheter and the urethral tube was introduced between the urethral meatus and glans penis. Beginning the 1st postoperative day (HBO2T was applied for 10 sessions during weekdays in 13 patients. Results: The mean age was 21 (±1.23 years and mean follow-up time was 10.1 (±2.1 months. In the group who received HBO2T postoperatively (n=13, a two-stage (orthoplasty buccal mucosal tube urethroplasty procedure was performed in 6 (46%, and the mean length of graft was 5.4 (±1.23 cm. In this group of 13 the success rate without any additional manipulations (urethrotomy intern, fistula repair was 54% (7/13. After additional manipulations, complete healing was achieved in 11 out of 13 patients (84.6%. In the group who did not receive HBO2T postoperatively (n=3, a two-stage procedure was performed in 1 patient (33%, and the mean length of graft was 8 (±5 cm. In this group of 3, complete healing was not achieved in any of these patients as a result of the hypospadias surgery. However, after the additional manipulations, complete healing was achieved in 1 patient (33%. Discussion: Given the promising rates of surgical success, postoperative HBO2T might be considered as a supportive treatment modality for adult patients with hypospadias who undergo buccal mucosal tube urethroplasty. Randomized controlled studies are needed.

  9. MultiModality Surgical and Hyperbaric Management of Mandibular Osteoradionecrosis

    International Nuclear Information System (INIS)

    Freiberger, John J.; Yoo, David S.; Lisle Dear, Guy de; McGraw, Thomas A.; Blakey, George H.; Padilla Burgos, Rebecca; Kraft, Kevin; Nelson, John W.; Moon, Richard E.; Piantadosi, Claude A.

    2009-01-01

    Purpose: To elucidate long-term outcomes in 65 consecutive patients meeting a uniform definition of mandibular osteoradionecrosis (ORN) treated with multimodality therapy including hyperbaric oxygen (HBO). Methods and Materials: Pretreatment, post-treatment and long-term follow-up of mandibular lesions with exposed bone were ranked by a systematic review of medical records and patient telephone calls. The ranking system was based on lesion diameter and number plus disease progression. Changes from pretreatment to post-treatment and follow-up were analyzed by Wilcoxon signed-rank tests. Improved wound survival, measured by time to relapse, defined as any less favorable rank after HBO treatment, was assessed by Kaplan-Meier analysis. Results: In all, 57 cases (88%) resolved or improved by lesion grade or progression and evolution criteria after HBO (p < 0.001). Four patients healed before surgery after HBO alone. Of 57 patients who experienced improvement, 41 had failed previous nonmultimodality therapy for 3 months and 26 for 6 months or more. A total of 43 patients were eligible for time-to-relapse survival analysis. Healing or improvement lasted a mean duration of 86.1 months (95% confidence interval [95% CI], 64.0-108.2) in nonsmokers (n = 20) vs. 15.8 months (95% CI, 8.4-23.2) in smokers (n = 14) versus 24.2 months (95% CI, 15.2-33.2) in patients with recurrent cancer (n = 9) (p = 0.002 by the log-rank method). Conclusions: Multimodality therapy using HBO is effective for ORN when less intensive therapies have failed. Although the healing rate in similarly affected patients not treated with HBO is unknown, the improvements seen with peri-operative HBO were durable provided that the patients remained cancer free and abstained from smoking.

  10. The effect of hyperbaric oxygen treatment on aspiration pneumonia.

    Science.gov (United States)

    Sahin, Sevtap Hekimoglu; Kanter, Mehmet; Ayvaz, Suleyman; Colak, Alkin; Aksu, Burhan; Guzel, Ahmet; Basaran, Umit Nusret; Erboga, Mustafa; Ozcan, Ali

    2011-08-01

    We have studied whether hyperbaric oxygen (HBO) prevents different pulmonary aspiration materials-induced lung injury in rats. The experiments were designed in 60 Sprague-Dawley rats, ranging in weight from 250 to 300 g, randomly allotted into one of six groups (n = 10): saline control, Biosorb Energy Plus (BIO), hydrochloric acid (HCl), saline + HBO treated, BIO + HBO treated, and HCl + HBO treated. Saline, BIO, HCl were injected into the lungs in a volume of 2 ml/kg. A total of seven HBO sessions were performed at 2,4 atm 100% oxygen for 90 min at 6-h intervals. Seven days later, rats were sacrificed, and both lungs in all groups were examined biochemically and histopathologically. Our findings show that HBO inhibits the inflammatory response reducing significantly (P fibrosis, granuloma, and necrosis formation in different pulmonary aspiration models. Pulmonar aspiration significantly increased the tissue HP content, malondialdehyde (MDA) levels and decreased (P < 0.05) the antioxidant enzyme (SOD, GSH-Px) activities. HBO treatment significantly (P < 0.05) decreased the elevated tissue HP content, and MDA levels and prevented inhibition of SOD, and GSH-Px (P < 0.05) enzymes in the tissues. Furthermore, there is a significant reduction in the activity of inducible nitric oxide synthase, TUNEL and arise in the expression of surfactant protein D in lung tissue of different pulmonary aspiration models with HBO therapy. It was concluded that HBO treatment might be beneficial in lung injury, therefore, shows potential for clinical use.

  11. Peripheral neuropathy may increase the risk for asymptomatic otic barotrauma during hyperbaric oxygen therapy: research report.

    Science.gov (United States)

    Mozdzanowski, Christopher; Perdrizet, George A

    2014-01-01

    Otic barotrauma (OBT) is an adverse event seen in patients receiving hyperbaric oxygen (HBO2) therapy. After encountering a case of painless tympanic perforation during HBO2 therapy of a diabetic patient with the diagnosis of neuropathic Wagner Grade III foot ulcer, we hypothesized that peripheral neuropathy of the lower extremity may be associated with an increased risk of asymptomatic OBT during HBO2 therapy. The medical records of all HBO2 patients during a one-year period of time were reviewed. Subjects were selected based on otoscopic documentation of OBT and divided into two groups based on the presence or absence of lower extremity peripheral neuropathy. Time to therapeutic compression, presence or absence of ear-related symptoms and modified Teed (mTeed) scores were compared between the two groups. A total of 38 patients with OBT, 18 neuropathic and 20 non-neuropathic, were identified. Asymptomatic OBT occurred more frequently in the neuropathic vs. non-neuropathic group (56% vs. 5%, p < 0.001). mTeed scores were significantly greater in the neuropathic vs. non-neuropathic group (mTeed 1, 30% vs. 61%; mTeed 2, 65% vs. 36%; mTeed 3, 4% vs. 3%; p = 0.032). Mean compression times were shorter in the neuropathic vs. non-neuropathic group (10. 5 +/- 1.8 vs. 14.4 +/- 3.3 minutes, p < 0.001). The presence of peripheral neuropathy of the lower extremity may be associated with a significantly greater incidence of asymptomatic otic barotrauma during HBO2 therapy.

  12. Hospital Acquired Thrombosis (HAT) Prevention in an Acute Hospital; A Single Centre Cross-Sectional Study

    LENUS (Irish Health Repository)

    Khan, MI

    2017-04-01

    Evidence based guidelines are effective in reducing incidence of venous thromboembolism (VTE) which is associated with morbidly, mortality and economic burden. This study aimed to identify the proportion of inpatients who had a VTE risk assessment (RA) performed and who received thromboprophylaxis (TP), in Cork University Hospital. There was no structured RA tool at the time; information was obtained from medical and drug charts to ascertain if a RA was performed. Patients were then RA by researchers and stratified as per NICE guidelines and the proportion who received TP was calculated. One thousand and nineteen inpatients were screened. Risk was documented in 24% of cases. TP was prescribed in 43.2% of inpatients. Following application of a RA tool >80% were at high risk of VTE with low risk of bleeding with TP prescription in 46.3% of inpatients. A national collaborative effort should be encouraged to develop a standardized approach for safe RA of inpatients and prescription of TP for prevention of HAT

  13. Hyperbaric oxygen therapy for the treatment of radiation-induced macular ischemia

    Directory of Open Access Journals (Sweden)

    Shamim A Haji

    2010-05-01

    Full Text Available Shamim A Haji1,2, Ronald EP Frenkel1,2,31Eye Research Foundation, Stuart, FL, USA; 2East Florida Eye Institute, Stuart, FL, USA; 3Bascom Palmer Eye Institute, Miami, FL, USAPurpose: To report a case of radiation-induced macular ischemia where vision and macular perfusion improved after hyperbaric oxygen (HBO therapy.Methods: A 62-year-old male patient developed radiation-induced macular ischemia after he was treated with radiation for brain glioma. The patient presented with best spectacle-corrected visual acuity (BSCVA acuity of 20/400 in his right eye. Optical coherence tomography (OCT showed central macular thickness of 468 μm. The patient received focal laser, intravitreal triamcinolone, and HBO therapy.Results: The patient’s vision improved from 20/400 to 20/100 after focal laser and intravitreal triamcinolone. His central macular thickness improved from 468 μm to 132 μm. After receiving HBO therapy, his VA improved to 20/50 and fluorescein angiography showed improvement in macular perfusion.Conclusion: HBO therapy improves macular perfusion in patients with radiation-induced macular ischemia.Keywords: macular ischemia, visual acuity, hyperbaric oxygen therapy, macular perfusion

  14. Estimation of gas-particle partitioning coefficients (Kp) of carcinogenic polycyclic aromatic hydrocarbons in carbonaceous aerosols collected at Chiang-Mai, Bangkok and Hat-Yai, Thailand.

    Science.gov (United States)

    Pongpiachan, Siwatt; Ho, Kin Fai; Cao, Junji

    2013-01-01

    To assess environmental contamination with carcinogens, carbonaceous compounds, water-soluble ionic species and trace gaseous species were identified and quantified every three hours for three days at three different atmospheric layers at the heart of Chiang-Mai, Bangkok and Hat-Yai from December 2006 to February 2007. A DRI Model 2001 Thermal/Optical Carbon Analyzer with the IMPROVE thermal/optical reflectance (TOR) protocol was used to quantify the organic carbon (OC) and elemental carbon (EC) contents in PM10. Diurnal and vertical variability was also carefully investigated. In general, OC and EC mass concentration showed the highest values at the monitoring period of 21.00-00.00 as consequences of human activities at night bazaar coupled with reduction of mixing layer, decreased wind speed and termination of photolysis at nighttime. Morning peaks of carbonaceous compounds were observed during the sampling period of 06:00-09:00, emphasizing the main contribution of traffic emission in the three cities. The estimation of incremental lifetime particulate matter exposure (ILPE) raises concern of high risk of carbonaceous accumulation over workers and residents living close to the observatory sites. The average values of incremental lifetime particulate matter exposure (ILPE) of total carbon at Baiyoke Suit Hotel and Baiyoke Sky Hotel are approximately ten times higher than those air samples collected at Prince of Songkla University Hat-Yai campus corpse incinerator and fish-can manufacturing factory but only slightly higher than those of rice straw burning in Songkla province. This indicates a high risk of developing lung cancer and other respiratory diseases across workers and residents living in high buildings located in Pratunam area. Using knowledge of carbonaceous fractions in PM10, one can estimate the gas-particle partitioning of polycyclic aromatic hydrocarbons (PAHs). Dachs-Eisenreich model highlights the crucial role of adsorption in gas

  15. daf-31 encodes the catalytic subunit of N alpha-acetyltransferase that regulates Caenorhabditis elegans development, metabolism and adult lifespan.

    Directory of Open Access Journals (Sweden)

    Di Chen

    2014-10-01

    Full Text Available The Caenorhabditis elegans dauer larva is a facultative state of diapause. Mutations affecting dauer signal transduction and morphogenesis have been reported. Of these, most that result in constitutive formation of dauer larvae are temperature-sensitive (ts. The daf-31 mutant was isolated in genetic screens looking for novel and underrepresented classes of mutants that form dauer and dauer-like larvae non-conditionally. Dauer-like larvae are arrested in development and have some, but not all, of the normal dauer characteristics. We show here that daf-31 mutants form dauer-like larvae under starvation conditions but are sensitive to SDS treatment. Moreover, metabolism is shifted to fat accumulation in daf-31 mutants. We cloned the daf-31 gene and it encodes an ortholog of the arrest-defective-1 protein (ARD1 that is the catalytic subunit of the major N alpha-acetyltransferase (NatA. A daf-31 promoter::GFP reporter gene indicates daf-31 is expressed in multiple tissues including neurons, pharynx, intestine and hypodermal cells. Interestingly, overexpression of daf-31 enhances the longevity phenotype of daf-2 mutants, which is dependent on the forkhead transcription factor (FOXO DAF-16. We demonstrate that overexpression of daf-31 stimulates the transcriptional activity of DAF-16 without influencing its subcellular localization. These data reveal an essential role of NatA in controlling C. elegans life history and also a novel interaction between ARD1 and FOXO transcription factors, which may contribute to understanding the function of ARD1 in mammals.

  16. Hyperbaric oxygen for carbon monoxide poisoning : a systematic review and critical analysis of the evidence.

    Science.gov (United States)

    Buckley, Nicholas A; Isbister, Geoffrey K; Stokes, Barrie; Juurlink, David N

    2005-01-01

    Poisoning with carbon monoxide (CO) is an important cause of unintentional and intentional injury worldwide. Hyperbaric oxygen (HBO) enhances CO elimination and has been postulated to reduce the incidence of neurological sequelae. These observations have led some clinicians to use HBO for selected patients with CO poisoning, although there is considerable variability in clinical practice. This article assesses the effectiveness of HBO compared with normobaric oxygen (NBO) for the prevention of neurological sequelae in patients with acute CO poisoning. The following databases were searched: MEDLINE (1966 to present), EMBASE (1980 to present), and the Controlled Trials Register of the Cochrane Collaboration, supplemented by a manual review of bibliographies of identified articles and discussion with recognised content experts. All randomised controlled trials involving people acutely poisoned with CO, regardless of severity, were examined. The primary analysis included all trials from which data could be extracted. Sensitivity analysis examined trials with better validity (defined using the validated instrument of Jadad) and those enrolling more severely poisoned patients. Two reviewers independently extracted from each trial, including information on the number of randomised patients, types of participants, the dose and duration of the intervention, and the prevalence of neurological sequelae at follow-up. A pooled odds ratio (OR) for the presence of neurological symptoms at 1-month follow-up was calculated using a random effects model. Bayesian models were also investigated to illustrate the degree of certainty about clinical effectiveness. Eight randomised controlled trials were identified. Two had no evaluable data and were excluded. The remaining trials were of varying quality and two have been published only as abstracts. The severity of CO poisoning varied among trials. At 1-month follow-up after treatment, sequelae possibly related to CO poisoning were

  17. Mycothiol acetyltransferase (Rv0819) of Mycobacterium tuberculosis is a potential biomarker for direct diagnosis of tuberculosis using patient serum specimens.

    Science.gov (United States)

    Zeitoun, H; Bahey-El-Din, M; Kassem, M A; Aboushleib, H M

    2017-12-01

    Mycobacterium tuberculosis infection constitutes a global threat that results in significant morbidity and mortality worldwide. Efficient and early diagnosis of tuberculosis (TB) is of paramount importance for successful treatment. The aim of the current study is to investigate the mycobacterial mycothiol acetyltransferase Rv0819 as a potential novel biomarker for the diagnosis of active TB infection. The gene encoding Rv0819 was cloned and successfully expressed in Escherichia coli. The recombinant Rv0819 was purified using metal affinity chromatography and was used to raise murine polyclonal antibodies against Rv0819. The raised antibodies were employed for direct detection of Rv0819 in patient serum samples using dot blot assay and competitive enzyme-linked immunosorbent assay (ELISA). Serum samples were obtained from 68 confirmed new TB patients and 35 healthy volunteers as negative controls. The dot blot assay showed sensitivity of 64·7% and specificity of 100%, whereas the competitive ELISA assay showed lower sensitivity (54·4%) and specificity (88·57%). The overall sensitivity of the combined results of the two tests was found to be 89·7%. Overall, the mycobacterial Rv0819 is a potential TB serum biomarker that can be exploited, in combination with other TB biomarkers, for efficient and reliable diagnosis of active TB infection. The early and accurate diagnosis of tuberculosis infection is of paramount importance for initiating treatment and avoiding clinical complications. Most current diagnostic tests have poor sensitivity and/or specificity and in many cases they are too expensive for routine diagnostic testing in resource-limited settings. In the current study, we examined a novel mycobacterial serum biomarker, namely mycothiol acetyltransferase Rv0819. The antigen was detectable in serum specimens of a significant number of tuberculosis patients. This article proves the importance of Rv0819 and paves the way towards its future use as a useful

  18. The Acetyl Group Buffering Action of Carnitine Acetyltransferase Offsets Macronutrient-Induced Lysine Acetylation of Mitochondrial Proteins

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    Michael N. Davies

    2016-01-01

    Full Text Available Lysine acetylation (AcK, a posttranslational modification wherein a two-carbon acetyl group binds covalently to a lysine residue, occurs prominently on mitochondrial proteins and has been linked to metabolic dysfunction. An emergent theory suggests mitochondrial AcK occurs via mass action rather than targeted catalysis. To test this hypothesis, we performed mass spectrometry-based acetylproteomic analyses of quadriceps muscles from mice with skeletal muscle-specific deficiency of carnitine acetyltransferase (CrAT, an enzyme that buffers the mitochondrial acetyl-CoA pool by converting short-chain acyl-CoAs to their membrane permeant acylcarnitine counterparts. CrAT deficiency increased tissue acetyl-CoA levels and susceptibility to diet-induced AcK of broad-ranging mitochondrial proteins, coincident with diminished whole body glucose control. Sub-compartment acetylproteome analyses of muscles from obese mice and humans showed remarkable overrepresentation of mitochondrial matrix proteins. These findings reveal roles for CrAT and L-carnitine in modulating the muscle acetylproteome and provide strong experimental evidence favoring the nonenzymatic carbon pressure model of mitochondrial AcK.

  19. United States Air Force Summer Faculty Research Program, 1988. Program Technical Report. Volume 4

    Science.gov (United States)

    1988-12-01

    keratin rich regions of the stratum corneum. Evidently the proteins of the RBC are y= unlike keratin! Of more interest to hyoerbaric oxygen. HBO. theraoy ...San Francisco State University. Prooo ed Patient Protocol vs. Conventional HBO Theraoy : Consider a patient requiring HBO for a problem wound on a

  20. The Epigenome as a therapeutic target for Parkinson's disease

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    Shane V Hegarty

    2016-01-01

    Full Text Available Parkinson's disease (PD is a common, progressive neurodegenerative disease characterised by degeneration of nigrostriatal dopaminergic neurons, aggregation of α-synuclein and motor symptoms. Current dopamine-replacement strategies provide symptomatic relief, however their effectiveness wear off over time and their prolonged use leads to disabling side-effects in PD patients. There is therefore a critical need to develop new drugs and drug targets to protect dopaminergic neurons and their axons from degeneration in PD. Over recent years, there has been robust evidence generated showing that epigenetic dysregulation occurs in PD patients, and that epigenetic modulation is a promising therapeutic approach for PD. This article first discusses the present evidence implicating global, and dopaminergic neuron-specific, alterations in the methylome in PD, and the therapeutic potential of pharmacologically targeting the methylome. It then focuses on another mechanism of epigenetic regulation, histone acetylation, and describes how the histone acetyltransferase (HAT and histone deacetylase (HDAC enzymes that mediate this process are attractive therapeutic targets for PD. It discusses the use of activators and/or inhibitors of HDACs and HATs in models of PD, and how these approaches for the selective modulation of histone acetylation elicit neuroprotective effects. Finally, it outlines the potential of employing small molecule epigenetic modulators as neuroprotective therapies for PD, and the future research that will be required to determine and realise this therapeutic potential.

  1. The impact of hyperbaric oxygen therapy on serological values of vascular endothelial growth factor (VEGF and basic fibroblast growth factor (bFGF

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    Ziebura Thomas

    2010-12-01

    Full Text Available Abstract Background Hyperbaric oxygen (HBO therapy is an effective adjunct treatment for ischemic disorders such as chronic infection or chronic wounds. It combines hyperoxic effects with the stimulating potential of post-therapeutic reactive hypoxia. As its crucial effects, stimulation of fibroblast growth, induction of collagen synthesis and the initiation of angiogenesis are discussed. Angiogenesis is a multistage process resulting in the growth of blood vessels. It includes degradation of extracellular matrix, proliferation and migration of different cell populations and finally formation of new vessel structures. This complex chain of procedures is orchestrated by different cytokines and growth factors. Crucial mediators of angiogenesis are basic fibroblast growth factor (bFGF and vascular endothelial growth factor (VEGF; their in-vivo function is still not fully understood. Methods Forty-three patients suffering from sudden sensorineural hearing loss or tinnitus were treated with HBO. The therapy included 10 sessions of 90 minutes each, one session a day. Serological levels of bFGF and VEGF were assessed by enzyme-linked immunosorbent assays performed according to the manufacturer's instructions on day 1, 2, 5 and 10 of HBO therapy and were compared to mean values of the control group, related to the patient's age and sex, and their development observed over the ten days of HBO. Results There was no sex- or age dependency of bFGF observed in the present study, whereas under HBO our results showed a significant mitigation of the bFGF concentration. In the present data, there was no connection between the VEGF concentration and the patients' ages. Women showed significantly higher levels of VEGF. There was no significant change of VEGF concentration or the VEGF/bFGF ratio during HBO. All scored results varied within the range of standard values as described in the current literature. Conclusions A significant effect of HBO on serum

  2. Inhibition of hypoxia-associated response and kynurenine production in response to hyperbaric oxygen as mechanisms involved in protection against experimental cerebral malaria.

    Science.gov (United States)

    Bastos, Marcele F; Kayano, Ana Carolina A V; Silva-Filho, João Luiz; Dos-Santos, João Conrado K; Judice, Carla; Blanco, Yara C; Shryock, Nathaniel; Sercundes, Michelle K; Ortolan, Luana S; Francelin, Carolina; Leite, Juliana A; Oliveira, Rafaella; Elias, Rosa M; Câmara, Niels O S; Lopes, Stefanie C P; Albrecht, Letusa; Farias, Alessandro S; Vicente, Cristina P; Werneck, Claudio C; Giorgio, Selma; Verinaud, Liana; Epiphanio, Sabrina; Marinho, Claudio R F; Lalwani, Pritesh; Amino, Rogerio; Aliberti, Julio; Costa, Fabio T M

    2018-03-20

    Cerebral malaria (CM) is a multifactorial syndrome involving an exacerbated proinflammatory status, endothelial cell activation, coagulopathy, hypoxia, and accumulation of leukocytes and parasites in the brain microvasculature. Despite significant improvements in malaria control, 15% of mortality is still observed in CM cases, and 25% of survivors develop neurologic sequelae for life-even after appropriate antimalarial therapy. A treatment that ameliorates CM clinical signs, resulting in complete healing, is urgently needed. Previously, we showed a hyperbaric oxygen (HBO)-protective effect against experimental CM. Here, we provide molecular evidence that HBO targets brain endothelial cells by decreasing their activation and inhibits parasite and leukocyte accumulation, thus improving cerebral microcirculatory blood flow. HBO treatment increased the expression of aryl hydrocarbon receptor over hypoxia-inducible factor 1-α (HIF-1α), an oxygen-sensitive cytosolic receptor, along with decreased indoleamine 2,3-dioxygenase 1 expression and kynurenine levels. Moreover, ablation of HIF-1α expression in endothelial cells in mice conferred protection against CM and improved survival. We propose that HBO should be pursued as an adjunctive therapy in CM patients to prolong survival and diminish deleterious proinflammatory reaction. Furthermore, our data support the use of HBO in therapeutic strategies to improve outcomes of non-CM disorders affecting the brain.-Bastos, M. F., Kayano, A. C. A. V., Silva-Filho, J. L., Dos-Santos, J. C. K., Judice, C., Blanco, Y. C., Shryock, N., Sercundes, M. K., Ortolan, L. S., Francelin, C., Leite, J. A., Oliveira, R., Elias, R. M., Câmara, N. O. S., Lopes, S. C. P., Albrecht, L., Farias, A. S., Vicente, C. P., Werneck, C. C., Giorgio, S., Verinaud, L., Epiphanio, S., Marinho, C. R. F., Lalwani, P., Amino, R., Aliberti, J., Costa, F. T. M. Inhibition of hypoxia-associated response and kynurenine production in response to hyperbaric oxygen

  3. Hyperoxic treatment induces mesenchymal-to-epithelial transition in a rat adenocarcinoma model.

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    Ingrid Moen

    Full Text Available Tumor hypoxia is relevant for tumor growth, metabolism and epithelial-to-mesenchymal transition (EMT. We report that hyperbaric oxygen (HBO treatment induced mesenchymal-to-epithelial transition (MET in a dimethyl-alpha-benzantracene induced mammary rat adenocarcinoma model, and the MET was associated with extensive coordinated gene expression changes and less aggressive tumors. One group of tumor bearing rats was exposed to HBO (2 bar, pO(2 = 2 bar, 4 exposures à 90 minutes, whereas the control group was housed under normal atmosphere (1 bar, pO(2 = 0.2 bar. Treatment effects were determined by assessment of tumor growth, tumor vascularisation, tumor cell proliferation, cell death, collagen fibrils and gene expression profile. Tumor growth was significantly reduced (approximately 16% after HBO treatment compared to day 1 levels, whereas control tumors increased almost 100% in volume. Significant decreases in tumor cell proliferation, tumor blood vessels and collagen fibrils, together with an increase in cell death, are consistent with tumor growth reduction and tumor stroma influence after hyperoxic treatment. Gene expression profiling showed that HBO induced MET. In conclusion, hyperoxia induced MET with coordinated expression of gene modules involved in cell junctions and attachments together with a shift towards non-tumorigenic metabolism. This leads to more differentiated and less aggressive tumors, and indicates that oxygen per se might be an important factor in the "switches" of EMT and MET in vivo. HBO treatment also attenuated tumor growth and changed tumor stroma, by targeting the vascular system, having anti-proliferative and pro-apoptotic effects.

  4. Investigations of solution-processed charge generation unit with low concentration of small molecule doped in p-type/HAT-CN6 for tandem OLED

    International Nuclear Information System (INIS)

    Talik, N.A.; Yeoh, K.H.; Ng, C.Y.B.; Tan, C.Y.; Yap, B.K.

    2016-01-01

    We investigated the charge generation and injection mechanism in solution processed charge generation unit (CGU) used in our high performance tandem organic light emitting diode (OLED) via capacitance–voltage (C–V) and current density–voltage (J–V) measurements. By doping 2 wt% of small molecule 1,1-bis-(4-bis(4-tolyl)-aminophenyl) cyclohexene (TAPC) into Poly (N-vinylcarbazole) (PVK) as p-type layer of the CGU, we obtained more than two folds improvement in the tandem device efficiency compared to single device. The performance improvement of the TAPC doped CGU could be attributed to low built-in potential, large vacuum level shift as well as high charge density for efficient charge generation. - Highlights: • Charge-generation and injection mechanism in CGU for tandem OLED is investigated. • Small molecule, TAPC doped in p-type/HAT-CN 6 has been used for tandem OLED. • The improvement attributes to the lower V bi and larger ΔV L in doped layer. • Narrower W and high carrier density also contribute to efficiency improvement.

  5. Hyperbaric oxygen therapy and surgical delay improve flap survival of reverse pedicle flaps for lower third leg and foot reconstruction

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    Pradeoth Mukundan Korambayil

    2015-06-01

    Full Text Available Aim: The purpose of the study is to present a management protocol for various types of soft tissue defects of the distal third region of leg and foot treated with pedicle flaps, by including hyperbaric oxygen (HBO therapy in the treatment regimen with flap delay. Methods: We present a prospective study of 23 patients with various types of soft tissue defects of the foot, and lower third of leg managed in our institution from December 2012 to December 2013. All soft tissue defects were treated by a reverse pedicle flap. Twelve patients were managed with flap delay with HBO therapy and 11 patients with immediate flaps without HBO therapy. The postoperative period, hospital course, and follow-up were documented. Results: Of 12 patients with flap delay and HBO, 10 patients did not suffer any complications secondary to flap transfer. One patient had discoloration of the tip of the flap, which settled without the intervention, and 1 patient had recurrent abscess formation, which required debridement and closure. Of 11 patients with direct transfer, 6 patients presented with complications including flap congestion, partial flap loss, and tip necrosis, which required secondary intervention. Conclusion: HBO therapy is a useful adjunct in flap delay of the reverse pedicle flap for soft tissue reconstruction of the lower third of the leg and foot regions.

  6. Interrelations between blood-brain barrier permeability and matrix metalloproteinases are differently affected by tissue plasminogen activator and hyperoxia in a rat model of embolic stroke

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    Michalski Dominik

    2012-01-01

    Full Text Available Abstract Background In ischemic stroke, blood-brain barrier (BBB regulations, typically involving matrix metalloproteinases (MMPs and inhibitors (TIMPs as mediators, became interesting since tissue plasminogen activator (tPA-related BBB breakdown with risk of secondary hemorrhage was considered to involve these mediators too. Despite high clinical relevance, detailed interactions are purely understood. After a pilot study addressing hyperoxia as potential neuroprotective co-treatment to tPA, we analyzed interrelations between BBB permeability (BBB-P, MMPs and TIMPs. Findings Rats underwent embolic middle cerebral artery occlusion (eMCAO and treatment with normobaric (NBO or hyperbaric oxygen (HBO, tPA, tPA+HBO, or no treatment. BBB-P was assessed by intravenously applied FITC-albumin at 4 or 24 hours. MMP-2/-9 and TIMP-1/-2 serum levels were determined at 5 or 25 hours. Time point-corrected partial correlations were used to explore interrelations of BBB-P in ischemic regions (extra-/intravasal FITC-albumin ratio and related serum markers. BBB-P correlated positively with MMP-2 and MMP-9 in controls, whereas hyperoxia led to an inverse association, most pronounced for HBO/MMP-9 (r = -0.606; P Conclusions HBO was found to reverse the positively directed interrelation of BBB-P and MMPs after eMCAO, but this effect failed to sustain in the expected amount when HBO and tPA were given simultaneously.

  7. Hyperbaric Oxygen Therapy as a Sole Agent Is Not Immunosuppressant in a Highly Immunogenic Mouse Model

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    Adam Gassas

    2011-01-01

    Full Text Available Background. Hyperbaric oxygen (HBO therapy, which is used for many conditions, may also have immunosuppressive effects and could be used for prevention or treatment of graft-versus-host disease (GvHD. If HBO is immunosuppressant, then we hypothesize that HBO therapy will delay the T-cell mediated skin graft rejection. Methods. C57/BL6 black-coated (H2B mice received skin graft from CBA (H2D white-coated mice. Mice were treated with either 19 session of 240 kpa oxygen or 29 session of 300 kpa oxygen, for 90 minutes. Mice were housed either 4 per cage or separately, to prevent friction and mechanical factors that may affect graft survival. Skin grafts were assessed daily. Results. There was no difference in length of graft survival between mice that received either regimens of HBO therapy and mice that did not receive HBO therapy. Conclusions. HBO therapy, as a sole agent, did not delay skin graft rejection in a highly immunogenic mouse model.

  8. Benefits of hyperbaric oxygen pretreatment for decompression sickness in Bama pigs.

    Science.gov (United States)

    Qing, Long; Yi, Hong-Jie; Wang, Ye-Wei; Zhou, Quan; Ariyadewa, Dinesh K; Xu, Wei-Gang

    2018-03-07

    Decompression sickness (DCS) occurs when ambient pressure is severely reduced during diving and aviation. Hyperbaric oxygen (HBO) pretreatment has been shown to exert beneficial effects on DCS in rats via heat-shock proteins (HSPs). We hypothesized that HBO pretreatment will also reduce DCS via HSPs in swine models. In the first part of our investigation, six swine were subjected to a session of HBO treatment. HSP32, 60, 70 and 90 were detected, before and at 6, 12, 18, 24 and 30 h following exposure in lymphocytes. In the second part of our investigation, another 10 swine were randomly assigned into two groups (five per group). All swine were subjected to two simulated air dives in a hyperbaric chamber with an interval of 7 days. Eighteen hours before each dive, the swine were pretreated with HBO or air: the first group received air pretreatment prior to the first dive and HBO pretreatment prior to the second; the second group were pretreated with HBO first and then air. Bubble loads, skin lesions, inflammation and endothelial markers were detected after each dive. In lymphocytes, all HSPs increased significantly ( P <0.05), with the greatest expression appearing at 18 h for HSP32 and 70. HBO pretreatment significantly reduced all the determined changes compared with air pretreatment. The results demonstrate that a single exposure to HBO 18 h prior to diving effectively protects against DCS in the swine model, possibly via induction of HSPs. © 2018. Published by The Company of Biologists Ltd.

  9. The neuroprotective effect of hyperbaric oxygen treatment on laser-induced retinal damage in rats

    Science.gov (United States)

    Vishnevskia-Dai, Victoria; Belokopytov, Mark; Dubinsky, Galina; Nachum, Gal; Avni, Isaac; Belkin, Michael; Rosner, Mordechai

    2005-04-01

    Retinal damage induced by mechanical trauma, ischemia or laser photocoagulation increases considerably by secondary degeneration processes. The spread of damage may be ameliorated by neuroprotection that is aimed at reducing the extent of the secondary degeneration and promote healing processes. Hyperbaric oxygen (HBO) treatment consists of inspiration of oxygen at higher than one absolute atmospheric pressure. Improved neural function was observed in patients with acute brain trauma or ischemia treated with HBO. This study was designed to evaluate the neuroprotective effect of hyperbaric oxygen (HBO) on laser induced retinal damage in a rat model. Standard argon laser lesions were created in 25 pigmented rats divided into three groups: Ten rats were treated immediately after the irradiation with HBO three times during the first 24 hr followed by 12 consecutive daily treatments. Five rats received a shorter treatment regimen of 10 consecutive HBO treatments. The control group (10 rats) underwent the laser damage with no additional treatment. The retinal lesions were evaluated 20 days after the injury. All outcome measures were improved by the longer HBO treatment (Ptreatment was less effective, showing an increase only in nuclei density at the central area of lesion (Pretinal damage in a rat model. In the range of HBO exposures studied, longer exposure provides more neuroprotection. These results encourage further evaluation of the potential therapeutic use of hyperbaric oxygen in diseases and injuries of the retina.

  10. Interleaved quantitative BOLD: Combining extravascular R2' - and intravascular R2-measurements for estimation of deoxygenated blood volume and hemoglobin oxygen saturation.

    Science.gov (United States)

    Lee, Hyunyeol; Englund, Erin K; Wehrli, Felix W

    2018-03-23

    Quantitative BOLD (qBOLD), a non-invasive MRI method for assessment of hemodynamic and metabolic properties of the brain in the baseline state, provides spatial maps of deoxygenated blood volume fraction (DBV) and hemoglobin oxygen saturation (HbO 2 ) by means of an analytical model for the temporal evolution of free-induction-decay signals in the extravascular compartment. However, mutual coupling between DBV and HbO 2 in the signal model results in considerable estimation uncertainty precluding achievement of a unique set of solutions. To address this problem, we developed an interleaved qBOLD method (iqBOLD) that combines extravascular R 2 ' and intravascular R 2 mapping techniques so as to obtain prior knowledge for the two unknown parameters. To achieve these goals, asymmetric spin echo and velocity-selective spin-labeling (VSSL) modules were interleaved in a single pulse sequence. Prior to VSSL, arterial blood and CSF signals were suppressed to produce reliable estimates for cerebral venous blood volume fraction (CBV v ) as well as venous blood R 2 (to yield HbO 2 ). Parameter maps derived from the VSSL module were employed to initialize DBV and HbO 2 in the qBOLD processing. Numerical simulations and in vivo experiments at 3 T were performed to evaluate the performance of iqBOLD in comparison to the parent qBOLD method. Data obtained in eight healthy subjects yielded plausible values averaging 60.1 ± 3.3% for HbO 2 and 3.1 ± 0.5 and 2.0 ± 0.4% for DBV in gray and white matter, respectively. Furthermore, the results show that prior estimates of CBV v and HbO 2 from the VSSL component enhance the solution stability in the qBOLD processing, and thus suggest the feasibility of iqBOLD as a promising alternative to the conventional technique for quantifying neurometabolic parameters. Copyright © 2018. Published by Elsevier Inc.

  11. Histone deacetylases and their roles in mineralized tissue regeneration

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    Nam Cong-Nhat Huynh

    2017-12-01

    Full Text Available Histone acetylation is an important epigenetic mechanism that controls expression of certain genes. It includes non-sequence-based changes of chromosomal regional structure that can alter the expression of genes. Acetylation of histones is controlled by the activity of two groups of enzymes: the histone acetyltransferases (HATs and histone deacetylases (HDACs. HDACs remove acetyl groups from the histone tail, which alters its charge and thus promotes compaction of DNA in the nucleosome. HDACs render the chromatin structure into a more compact form of heterochromatin, which makes the genes inaccessible for transcription. By altering the transcriptional activity of bone-associated genes, HDACs control both osteogenesis and osteoclastogenesis. This review presents an overview of the function of HDACs in the modulation of bone formation. Special attention is paid to the use of HDAC inhibitors in mineralized tissue regeneration from cells of dental origin.

  12. Induction of autophagy by spermidine promotes longevity.

    Science.gov (United States)

    Eisenberg, Tobias; Knauer, Heide; Schauer, Alexandra; Büttner, Sabrina; Ruckenstuhl, Christoph; Carmona-Gutierrez, Didac; Ring, Julia; Schroeder, Sabrina; Magnes, Christoph; Antonacci, Lucia; Fussi, Heike; Deszcz, Luiza; Hartl, Regina; Schraml, Elisabeth; Criollo, Alfredo; Megalou, Evgenia; Weiskopf, Daniela; Laun, Peter; Heeren, Gino; Breitenbach, Michael; Grubeck-Loebenstein, Beatrix; Herker, Eva; Fahrenkrog, Birthe; Fröhlich, Kai-Uwe; Sinner, Frank; Tavernarakis, Nektarios; Minois, Nadege; Kroemer, Guido; Madeo, Frank

    2009-11-01

    Ageing results from complex genetically and epigenetically programmed processes that are elicited in part by noxious or stressful events that cause programmed cell death. Here, we report that administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extended the lifespan of yeast, flies and worms, and human immune cells. In addition, spermidine administration potently inhibited oxidative stress in ageing mice. In ageing yeast, spermidine treatment triggered epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), suppressing oxidative stress and necrosis. Conversely, depletion of endogenous polyamines led to hyperacetylation, generation of reactive oxygen species, early necrotic death and decreased lifespan. The altered acetylation status of the chromatin led to significant upregulation of various autophagy-related transcripts, triggering autophagy in yeast, flies, worms and human cells. Finally, we found that enhanced autophagy is crucial for polyamine-induced suppression of necrosis and enhanced longevity.

  13. Epigenetic changes modulate schistosome egg formation and are a novel target for reducing transmission of schistosomiasis.

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    Vitor Coutinho Carneiro

    2014-05-01

    Full Text Available Treatment and control of schistosomiasis relies on the only available drug, praziquantel, and the search for alternative chemotherapeutic agents is therefore urgent. Egg production is required for the transmission and immunopathology of schistosomiasis and females of S. mansoni lay 300 eggs daily. A large fraction of the total mRNA in the mature female worm encodes one eggshell protein, Smp14. We report that the nuclear receptors SmRXR1 and SmNR1 regulate Smp14 transcription through the recruitment of two histone acetyltransferases (HATs, SmGCN5 and SmCBP1. The treatment of HEK293 cells with histone deacetylase (HDAC inhibitors (NaB or TSA produced an 8-fold activation of the SmRXR1/SmNR1-mediated Smp14 promoter activity. Incubation with synthetic HAT inhibitors, including PU139, significantly impaired the Smp14 promoter activity in these cells. Worm pairs cultivated in the presence of PU139 exhibited limited expression of Smp14 mRNA and protein. ChIP analysis demonstrated chromatin condensation at the Smp14 promoter site in worms treated with PU139. ChIP also revealed the presence of H3K27me3 and the absence of RNA Pol II at the Smp14 promoter region in the PU139-treated worms. Most significantly, the PU139-mediated inhibition of Smp14 expression resulted in a significant number of abnormal eggs as well as defective eggs within the ootype. In addition, scanning electron microscopy revealed structural defects and unformed eggshells, and vitelline cell leakage was apparent. The dsRNAi-targeting of SmGCN5 or SmCBP1 significantly decreased Smp14 transcription and protein synthesis, which compromised the reproductive system of mature female worms, egg-laying and egg morphology. Our data strongly suggest that the inhibition of Smp14 expression targeting SmGCN5 and/or SmCBP1 represents a novel and effective strategy to control S. mansoni egg development.

  14. Investigations of solution-processed charge generation unit with low concentration of small molecule doped in p-type/HAT-CN{sub 6} for tandem OLED

    Energy Technology Data Exchange (ETDEWEB)

    Talik, N.A., E-mail: azrina_talik@hotmail.com [Low Dimensional Material Research Centre (LDMRC), Physics Dept., Faculty of Science, University of Malaya, 50603 Kuala Lumpur (Malaysia); Yeoh, K.H. [Low Dimensional Material Research Centre (LDMRC), Physics Dept., Faculty of Science, University of Malaya, 50603 Kuala Lumpur (Malaysia); Centre for Photonics and Advanced Materials Research (CPR), Lee Kong Chian Faculty of Engineering and Science, University Tunku Abdul Rahman, 43000 Kajang, Selangor (Malaysia); Ng, C.Y.B. [Low Dimensional Material Research Centre (LDMRC), Physics Dept., Faculty of Science, University of Malaya, 50603 Kuala Lumpur (Malaysia); Tan, C.Y. [Centre of Advanced Manufacturing & Material Processing (AMMP), Department of Mechanical Engineering, Faculty of Engineering, University of Malaya, 50603 Kuala Lumpur (Malaysia); Yap, B.K., E-mail: kbyap@uniten.edu.my [Centre of Microelectronic and Nano Engineering (CeMNE), College of Engineering, Universiti Tenaga Nasional, 43000 Kajang, Selangor (Malaysia)

    2016-01-15

    We investigated the charge generation and injection mechanism in solution processed charge generation unit (CGU) used in our high performance tandem organic light emitting diode (OLED) via capacitance–voltage (C–V) and current density–voltage (J–V) measurements. By doping 2 wt% of small molecule 1,1-bis-(4-bis(4-tolyl)-aminophenyl) cyclohexene (TAPC) into Poly (N-vinylcarbazole) (PVK) as p-type layer of the CGU, we obtained more than two folds improvement in the tandem device efficiency compared to single device. The performance improvement of the TAPC doped CGU could be attributed to low built-in potential, large vacuum level shift as well as high charge density for efficient charge generation. - Highlights: • Charge-generation and injection mechanism in CGU for tandem OLED is investigated. • Small molecule, TAPC doped in p-type/HAT-CN{sub 6} has been used for tandem OLED. • The improvement attributes to the lower V{sub bi} and larger ΔV{sub L} in doped layer. • Narrower W and high carrier density also contribute to efficiency improvement.

  15. Regional CBF in chronic stable TBI treated with hyperbaric oxygen.

    Science.gov (United States)

    Barrett, K F; Masel, B; Patterson, J; Scheibel, R S; Corson, K P; Mader, J T

    2004-01-01

    To investigate whether Hyperbaric Oxygen Therapy (HBO2) could improve neurologic deficits and regional cerebral blood flow (rCBF) in chronic traumatic brain injuries (TBI), the authors employed a nonrandomized control pilot trial. Five subjects, at least three years post head injury, received HBO2. Five head injured controls (HIC) were matched for age, sex, and type of injury. Five healthy subjects served as normal controls. Sixty-eight normal volunteers comprised a reference data bank against which to compare SPECT brain scans. HBO2 subjects received 120 HBO2 in blocks of 80 and 40 treatments with an interval five-month break. Normal controls underwent a single SPECT brain scan, HBO2, and repeat SPECT battery. TBI subjects were evaluated by neurologic, neuropsychometric, exercise testing, and pre and post study MRIs, or CT scans if MRI was contraindicated. Statistical Parametric Mapping was applied to SPECT scans for rCBF analysis. There were no significant objective changes in neurologic, neuropsychometric, exercise testing, MRIs, or rCBF. In this small pilot study, HBO2 did not effect clinical or regional cerebral blood flow improvement in TBI subjects.

  16. Pulse radiolysis study of the reactions of certain radicals with the oxyhemoglobin-methemoglobin system

    International Nuclear Information System (INIS)

    Gilles, Lucien; Haristoy, D.

    1981-01-01

    Hemoglobin occupies an important role as oxygen carrier in the respiratory chain. The autoxydation of oxyhemoglobin (HbO 2 ) into methemoglobin (HbFesup(III)) could perturb this chain unless the system acts as a source of O 2 - which could facilitate oxydation processes. The reactivity of the HbO 2 -HbFesup(III) system with short lived transients (O 2 - , CO 2 - ) was studied in order to gain some insight into this problem. The low reactivity of O 2 - with respect to both HbO 2 and HbFesup(III) shows that the autoxydation of HbO 2 in vivo could act as an O 2 - donor [fr

  17. Pulse radiolysis study of the reactions of certain radicals with the oxyhemoglobin-methemoglobin system

    International Nuclear Information System (INIS)

    Gilles, L.; Haristoy, D.

    1982-06-01

    Hemoglobin occupies an important role as oxygen carrier in the respiratory chain. The autoxydation of oxyhemoglobin (HbO 2 ) into methemoglobin (HbFesup(III)) could perturb this chain unless the system acts as a source of O 2 - which could facilitate oxydation processes. The reactivity of the HbO 2 -HbFesup(III) system with short lived transients (O 2 - , CO 2 - ) was studied in order to gain some insigh into this problem. The low reactivity of O 2 - with respect to both HbO 2 and HbFesup(III) shows that the autoxydation of HbO 2 in vivo could act as an O 2 - donor [fr

  18. Dual N- and C-terminal helices are required for endoplasmic reticulum and lipid droplet association of alcohol acetyltransferases in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Jyun-Liang Lin

    Full Text Available In the yeast Saccharomyces cerevisiae two alcohol acetyltransferases (AATases, Atf1 and Atf2, condense short chain alcohols with acetyl-CoA to produce volatile acetate esters. Such esters are, in large part, responsible for the distinctive flavors and aromas of fermented beverages including beer, wine, and sake. Atf1 and Atf2 localize to the endoplasmic reticulum (ER and Atf1 is known to localize to lipid droplets (LDs. The mechanism and function of these localizations are unknown. Here, we investigate potential mechanisms of Atf1 and Atf2 membrane association. Segments of the N- and C-terminal domains of Atf1 (residues 24-41 and 508-525, respectively are predicted to be amphipathic helices. Truncations of these helices revealed that the terminal domains are essential for ER and LD association. Moreover, mutations of the basic or hydrophobic residues in the N-terminal helix and hydrophobic residues in the C-terminal helix disrupted ER association and subsequent sorting from the ER to LDs. Similar amphipathic helices are found at both ends of Atf2, enabling ER and LD association. As was the case with Atf1, mutations to the N- and C-terminal helices of Atf2 prevented membrane association. Sequence comparison of the AATases from Saccharomyces, non-Saccharomyces yeast (K. lactis and P. anomala and fruits species (C. melo and S. lycopersicum showed that only AATases from Saccharomyces evolved terminal amphipathic helices. Heterologous expression of these orthologs in S. cerevisiae revealed that the absence of terminal amphipathic helices eliminates LD association. Combined, the results of this study suggest a common mechanism of membrane association for AATases via dual N- and C-terminal amphipathic helices.

  19. Breast cancer, heterocyclic aromatic amines from meat and N-acetyltransferase 2 genotype.

    Science.gov (United States)

    Delfino, R J; Sinha, R; Smith, C; West, J; White, E; Lin, H J; Liao, S Y; Gim, J S; Ma, H L; Butler, J; Anton-Culver, H

    2000-04-01

    Breast cancer risk has been hypothesized to increase with exposure to heterocyclic aromatic amines (HAAs) formed from cooking meat at high temperature. HAAs require enzymatic activation to bind to DNA and initiate carcinogenesis. N-acetyltransferase 2 (NAT2) enzyme activity may play a role, its rate determined by a polymorphic gene. We examined the effect of NAT2 genetic polymorphisms on breast cancer risk from exposure to meat by cooking method, doneness and estimated HAA [2-amino-1-methyl-6-phenylimidazole[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx)] intake. Women were recruited with suspicious breast masses and questionnaire data were collected prior to biopsy to blind subjects and interviewers to diagnoses. For 114 cases with breast cancer and 280 controls with benign breast disease, NAT2 genotype was determined using allele-specific PCR amplification to detect slow acetylator mutations. HAAs were estimated from interview data on meat type, cooking method and doneness, combined with a quantitative HAA database. Logistic regression models controlled for known risk factors, first including all controls, then 108 with no or low risk (normal breast or no hyperplasia) and finally 149 with high risk (hyperplasia, atypical hyperplasia, complex fibroadenomas). Meat effects were examined within NAT2 strata to assess interactions. We found no association between NAT2 and breast cancer. These Californian women ate more white than red meat (control median 46 versus 8 g/day). There were no significant associations of breast cancer with red meat for any doneness. White meat was significantly protective (>67 versus chicken, including well done, pan fried and barbecued chicken. MeIQx and DiMeIQx were not associated with breast cancer. A protective effect of PhIP was confounded after controlling for well done chicken. Results were unchanged using low or high risk controls or dropping

  20. "Das Konkrete ist das Abstrakte, an das man sich schließlich gewöhnt hat." (Laurent Schwartz) Über den Ablauf des mathematischen Verstehens

    Science.gov (United States)

    Lowsky, Martin

    Die im Titel genannte Aussage findet sich in den Lebenserinnerungen von Laurent Schwartz (1915-2002), einem der fruchtbarsten Mathematiker, Mitglied der Gruppe Bourbaki. Im Original lautet die Aussage: "un objet concret est un objet abstrait auquel on a fini par s'habituer." Schwartz erläutert sie am Beispiel des Integrals über {e^{-1/2{x^2}}} , das den Wert Wurzel aus 2π hat und in dem sich also die Zahlen e und π verknüpfen. Was Schwartz aber vor allem ausdrücken will, ist dies: Das mathematische Verständnisd geht langsam vor sich und es bedarf der Anstrengung. "Es ist eine Frage der Zeit und der Energie", sagt Schwartz, und gerade dies mache es so schwer, die höhere Mathematik unter das Volk zu bringen. Das Lernen und Lehren von Mathematik laufe eben mühevoll und langsam ab.

  1. Biphasic oxidation of oxy-hemoglobin in bloodstains.

    Directory of Open Access Journals (Sweden)

    Rolf H Bremmer

    Full Text Available BACKGROUND: In forensic science, age determination of bloodstains can be crucial in reconstructing crimes. Upon exiting the body, bloodstains transit from bright red to dark brown, which is attributed to oxidation of oxy-hemoglobin (HbO(2 to met-hemoglobin (met-Hb and hemichrome (HC. The fractions of HbO(2, met-Hb and HC in a bloodstain can be used for age determination of bloodstains. In this study, we further analyze the conversion of HbO(2 to met-Hb and HC, and determine the effect of temperature and humidity on the conversion rates. METHODOLOGY: The fractions of HbO(2, met-Hb and HC in a bloodstain, as determined by quantitative analysis of optical reflectance spectra (450-800 nm, were measured as function of age, temperature and humidity. Additionally, Optical Coherence Tomography around 1300 nm was used to confirm quantitative spectral analysis approach. CONCLUSIONS: The oxidation rate of HbO(2 in bloodstains is biphasic. At first, the oxidation of HbO(2 is rapid, but slows down after a few hours. These oxidation rates are strongly temperature dependent. However, the oxidation of HbO(2 seems to be independent of humidity, whereas the transition of met-Hb into HC strongly depends on humidity. Knowledge of these decay rates is indispensable for translating laboratory results into forensic practice, and to enable bloodstain age determination on the crime scene.

  2. CRTC1 Nuclear Translocation Following Learning Modulates Memory Strength via Exchange of Chromatin Remodeling Complexes on the Fgf1 Gene

    Directory of Open Access Journals (Sweden)

    Shusaku Uchida

    2017-01-01

    Full Text Available Summary: Memory is formed by synapse-to-nucleus communication that leads to regulation of gene transcription, but the identity and organizational logic of signaling pathways involved in this communication remain unclear. Here we find that the transcription cofactor CRTC1 is a critical determinant of sustained gene transcription and memory strength in the hippocampus. Following associative learning, synaptically localized CRTC1 is translocated to the nucleus and regulates Fgf1b transcription in an activity-dependent manner. After both weak and strong training, the HDAC3-N-CoR corepressor complex leaves the Fgf1b promoter and a complex involving the translocated CRTC1, phosphorylated CREB, and histone acetyltransferase CBP induces transient transcription. Strong training later substitutes KAT5 for CBP, a process that is dependent on CRTC1, but not on CREB phosphorylation. This in turn leads to long-lasting Fgf1b transcription and memory enhancement. Thus, memory strength relies on activity-dependent changes in chromatin and temporal regulation of gene transcription on specific CREB/CRTC1 gene targets. : Uchida et al. link CRTC1 synapse-to-nucleus shuttling in memory. Weak and strong training induce CRTC1 nuclear transport and transient Fgf1b transcription by a complex including CRTC1, CREB, and histone acetyltransferase CBP, whereas strong training alone maintains Fgf1b transcription through CRTC1-dependent substitution of KAT5 for CBP, leading to memory enhancement. Keywords: memory enhancement, long-term potentiation, hippocampus, nuclear transport, epigenetics, FGF1, CRTC1, KAT5/Tip60, HDAC3, CREB

  3. The early response of pineal N-acetyltransferase activity, melatonin and catecholamine levels in rats irradiated with gamma rays

    International Nuclear Information System (INIS)

    Kassayova, M.; Ahlersova, E.; Ahlers, I.; Pastorova, B.

    1995-01-01

    Male Wistar rats adapted to an artificial light-dark regimen were whole-body gamma-irradiated with a dose of 14.35 Gy. Irradiation, sham-irradiation and decapitation 30, 60 and 120 min after the exposure were performed between 2000 h and 0100 h in the darkness. The serotonin N-acetyltransferase activity (NAT), the concentration of melatonin and corticosterone were also determined. Ionizing radiation did not change the activity of NAT, the key enzyme of melatonin synthesis; however, it decreased the concentration of pineal melatonin. The concentration of pineal dopamine and norepinephrine decreased 30 and 120 min after exposure, while the concentration of epinephrine was elevated 30 min after irradiation, though later it was markedly decreased. The serum melatonin level was not changed but an increase in corticosterone level was observed. In the early period after exposure a decrease in pineal melatonin occurred, accompanied by a decrease in pineal catecholamines. On the contrary, in the phase of developed radiation injury the signs of increased melatonin synthesis were observed on days 3 and 4 after the exposure. (author) 6 figs., 25 refs

  4. Quantum-Classical Phase Transition of the Escape Rate of Two-Sublattice Antiferromagnetic Large Spins

    Science.gov (United States)

    Owerre, Solomon Akaraka; Paranjape, M. B.

    2014-11-01

    The Hamiltonian of a two-sublattice antiferromagnetic spins, with single (hard-axis) and double ion anisotropies described by H = J {\\hat S}1...\\hatS 2-2Jz \\hat {S}1z\\hat {S}2z+K(\\hat {S}1z2 +\\hat {S}2z2) is investigated using the method of effective potential. The problem is mapped to a single particle quantum-mechanical Hamiltonian in terms of the relative coordinate and reduced mass. We study the quantum-classical phase transition of the escape rate of this model. We show that the first-order phase transition for this model sets in at the critical value Jc = (Kc+Jz, c)/2 while for the anisotropic Heisenberg coupling H = J(S1xS2x +S1yS2y) + JzS1zS2z + K(S1z2+ S2z2) we obtain Jc = (2Kc-Jz, c)/3. The phase diagrams of the transition are also studied.

  5. Effects of hyperbaric oxygen and nerve growth factor on the long-term neural behavior of neonatal rats with hypoxic ischemic brain damage.

    Science.gov (United States)

    Wei, Lixia; Ren, Qing; Zhang, Yongjun; Wang, Jiwen

    2017-04-01

    To evaluate the effects of HBO (Hyperbaric oxygen) and NGF (Nerve growth factor) on the long-term neural behavior of neonatal rats with HIBD (Neonatal hypoxic ischemic brain damage). The HIBD model was produced by ligating the right common carotid artery of 7 days old SD (Sprague-Dawley) rats followed by 8% O2 + 92% N2 for 2h. Totally 40 rats were randomly divided into 5 groups including sham-operated group, HIBD control group, HBO treated group, NGF treated group and NGF + HBO treated group. The learning and memory ability of these rats was evaluated by Morris water maze at 30 days after birth, and sensory motor function was assessed by experiments of foot error and limb placement at 42 days after birth. The escape latency of HBO treated group, NGF treated group and NGF + HBO treated group was shorter than that of HIBD control group (pmemory ability and sensory motor function in neonatal rats after hypoxic ischemic brain damage.

  6. Study by γ radiolysis and pulsed radiolysis of the reactivity of the superoxide ion in the oxyhemoglobin-methemoglobin system

    International Nuclear Information System (INIS)

    Haristoy, Didier.

    1976-01-01

    γ radiolysis of aqueous solutions of methemoglobin (MetHb) in the presence of formate ions, shows that only 25% of the total protein is reduced in oxyhemoglobin (HbO 2 ) by superoxide ions O 2 - according to the reaction MetHb+O 2 - →HbO 2 . The result can be attributed neither to the reactions of O 2 - with HbO 2 , nor the oxidation of HbO 2 by H 2 O 2 produced in the radiolysis of water and by dismutation of O 2 - . Pulse radiolysis studies of this reaction strongly suggest the formation of a transient complex 'MetHbO 2 - ' during the reaction. In addition to the well known self-oxidation of HbO 2 , these results show the existence of an equilibrium between HbO 2 and MetHb+O 2 - . Such an equilibrium could give rise, 'in vivo' to a nearly steady concentration of superoxide ions which could initiate a reaction favoring oxidation by oxygen [fr

  7. Hyperbaric oxygen therapy in periodontal diseases

    Directory of Open Access Journals (Sweden)

    Swapna A. Mahale

    2013-01-01

    Full Text Available Hyperbaric oxygen (HBO 2 has been successfully used in several medical fields. The therapeutic effect is related to elevated partial oxygen pressure in the tissues. The pressure itself enhances oxygen solubility in the tissue fluids. HBO 2 has shown to affect angiogenesis, bone metabolism and bone turnover. Studies have been conducted to analyze the effects of HBO 2 therapy on periodontal disease. HBO 2 increases local oxygen distribution, especially at the base of the periodontal pocket, which inhibits the growth of anaerobic bacteria and allows the ischemic tissues to receive an adequate intake of oxygen sufficient for a rapid recovery of cell metabolism. It is increasingly being accepted as a beneficial adjunct to diverse clinical conditions. Nonhealing ulcers, chronic wounds and refractory osteomyelitis are a few conditions for which HBO therapy (HBOT has been extensively tried out. The dental surgeons have found a good ally in HBOT in managing dental condition.

  8. 16:9 Podcast #02: Sex i populærkulturen (2:2)

    DEFF Research Database (Denmark)

    2018-01-01

    It’s not porn, it’s HBO! Eller er det en Trierfilm? I denne anden podcast om sex i populærkulturen bevæger Isak Thorsen og Jakob Isak Nielsen sig væk fra dansk film i 70erne for at causere over forekomsten af eksplicit seksualitet i en bredere film- og tv-historisk kontekst. De to gange Isak rund...... såvel nyere som ældre kunstfilm, ligesom de via nedslag i Game of Thrones (HBO, 2011- ) og Tell Me You Love Me (HBO, 2007) diskuterer to vidt forskellige funktioner, som eksplicit seksualitet kan have i HBO-serier.......It’s not porn, it’s HBO! Eller er det en Trierfilm? I denne anden podcast om sex i populærkulturen bevæger Isak Thorsen og Jakob Isak Nielsen sig væk fra dansk film i 70erne for at causere over forekomsten af eksplicit seksualitet i en bredere film- og tv-historisk kontekst. De to gange Isak runder...

  9. Spatial and social factors associated with transportation and recreational physical activity among adults in Hat Yai City, Songkhla,Thailand.

    Science.gov (United States)

    Churangsarit, Saowaphan; Chongsuvivatwong, Virasakdi

    2011-08-01

    Transportation physical activity (TPA) and recreational physical activity (RPA) in an urban area can be sources of physical activity (PA) in addition to working. This study was conducted in Hat Yai City Municipality, the fourth most populous city in Thailand, to describe the magnitude of these physical activities and identify their associated factors. 369 adults were selected from a random sampling of registered households. Based on the Global Physical Activity Questionnaire (GPAQ), subjects were interviewed on their modes of TPA and RPA during the past week. Hurdle regression was used to examine predictors for having PA separately from predictor of intensity of PA among the active. Metabolic equivalent (MET) of TPA and RPA were computed. Prevalence of not having TPA and RPA were 71.3% and 45.8%, respectively. TPA and RPA contributed 1.5% and 9.2% of total PA. Active commuters were more common in females 40 or more years old, less sedentary persons, and those living near shopping places. Persons having RPA were more likely to be less sedentary, whereas the intensity of RPA was higher among single persons and males. TPA and RPA in this study area were uncommon. Further strategies are needed to improve the situation, especially among sedentary persons.

  10. Characterization of the serine acetyltransferase gene family of Vitis vinifera uncovers differences in regulation of OAS synthesis in woody plants

    Science.gov (United States)

    Tavares, Sílvia; Wirtz, Markus; Beier, Marcel P.; Bogs, Jochen; Hell, Rüdiger; Amâncio, Sara

    2015-01-01

    In higher plants cysteine biosynthesis is catalyzed by O-acetylserine(thiol)lyase (OASTL) and represents the last step of the assimilatory sulfate reduction pathway. It is mainly regulated by provision of O-acetylserine (OAS), the nitrogen/carbon containing backbone for fixation of reduced sulfur. OAS is synthesized by Serine acetyltransferase (SERAT), which reversibly interacts with OASTL in the cysteine synthase complex (CSC). In this study we identify and characterize the SERAT gene family of the crop plant Vitis vinifera. The identified four members of the VvSERAT protein family are assigned to three distinct groups upon their sequence similarities to Arabidopsis SERATs. Expression of fluorescently labeled VvSERAT proteins uncover that the sub-cellular localization of VvSERAT1;1 and VvSERAT3;1 is the cytosol and that VvSERAT2;1 and VvSERAT2;2 localize in addition in plastids and mitochondria, respectively. The purified VvSERATs of group 1 and 2 have higher enzymatic activity than VvSERAT3;1, which display a characteristic C-terminal extension also present in AtSERAT3;1. VvSERAT1;1 and VvSERAT2;2 are evidenced to form the CSC. CSC formation activates VvSERAT2;2, by releasing CSC-associated VvSERAT2;2 from cysteine inhibition. Thus, subcellular distribution of SERAT isoforms and CSC formation in cytosol and mitochondria is conserved between Arabidopsis and grapevine. Surprisingly, VvSERAT2;1 lack the canonical C-terminal tail of plant SERATs, does not form the CSC and is almost insensitive to cysteine inhibition (IC50 = 1.9 mM cysteine). Upon sulfate depletion VvSERAT2;1 is strongly induced at the transcriptional level, while transcription of other VvSERATs is almost unaffected in sulfate deprived grapevine cell suspension cultures. Application of abiotic stresses to soil grown grapevine plants revealed isoform-specific induction of VvSERAT2;1 in leaves upon drought, whereas high light- or temperature- stress hardly trigger VvSERAT2;1 transcription. PMID:25741355

  11. Clinical and epidemiological characteristics of acute respiratory virus infections in Vietnamese children.

    Science.gov (United States)

    Tran, D N; Trinh, Q D; Pham, N T K; Vu, M P; Ha, M T; Nguyen, T Q N; Okitsu, S; Hayakawa, S; Mizuguchi, M; Ushijima, H

    2016-02-01

    Information about viral acute respiratory infections (ARIs) is essential for prevention, diagnosis and treatment, but it is limited in tropical developing countries. This study described the clinical and epidemiological characteristics of ARIs in children hospitalized in Vietnam. Nasopharyngeal samples were collected from children with ARIs at Ho Chi Minh City Children's Hospital 2 between April 2010 and May 2011 in order to detect respiratory viruses by polymerase chain reaction. Viruses were found in 64% of 1082 patients, with 12% being co-infections. The leading detected viruses were human rhinovirus (HRV; 30%), respiratory syncytial virus (RSV; 23·8%), and human bocavirus (HBoV; 7·2%). HRV was detected all year round, while RSV epidemics occurred mainly in the rainy season. Influenza A (FluA) was found in both seasons. The other viruses were predominant in the dry season. HRV was identified in children of all age groups. RSV, parainfluenza virus (PIV) 1, PIV3 and HBoV, and FluA were detected predominantly in children aged 24 months, respectively. Significant associations were found between PIV1 with croup (P < 0·005) and RSV with bronchiolitis (P < 0·005). HBoV and HRV were associated with hypoxia (P < 0·05) and RSV with retraction (P < 0·05). HRV, RSV, and HBoV were detected most frequently and they may increase the severity of ARIs in children.

  12. Molecular Diagnosis Of Human Boca virus Gastroenteritis

    International Nuclear Information System (INIS)

    Kassem, N.N.; Kamel, E.M.; Ismail, G.A.; Emam, E.K.; Saber, S.M.; EL Ashry, M.A.

    2012-01-01

    The idea that human boca virus (HBoV) infection possibly plays a role in gastroenteritis has been suggested because of the frequent manifestation of gastrointestinal symptoms. The purpose of this study was to investigate the role of HBoV In children with gastroenteritis. We studied the etiologic agents in 100 fecal samples in children suffered from acute gastroenteritis. Bacterial etiological agents were dtected by conventional bacteriological culture, and viral etiologic agents were detected by rotavirus latex agglutination and conventional PCR for HBoV and enteric adenovirus. Enteropathogenic E-Coli (EPEC) was detected in 4% of cases. Rotatavirus, enteric adenovirus and co infection between rotavirus and adenovirus were detected in 14%, 6% and 2% respectively. Human boca virus was detected in 1% of cases without associated respiratory symptoms or co infection with other pathogen which suggests its role in children gastroenteritis

  13. Structure of noncoding RNA is a determinant of function of RNA binding proteins in transcriptional regulation

    Directory of Open Access Journals (Sweden)

    Oyoshi Takanori

    2012-01-01

    Full Text Available Abstract The majority of the noncoding regions of mammalian genomes have been found to be transcribed to generate noncoding RNAs (ncRNAs, resulting in intense interest in their biological roles. During the past decade, numerous ncRNAs and aptamers have been identified as regulators of transcription. 6S RNA, first described as a ncRNA in E. coli, mimics an open promoter structure, which has a large bulge with two hairpin/stalk structures that regulate transcription through interactions with RNA polymerase. B2 RNA, which has stem-loops and unstructured single-stranded regions, represses transcription of mRNA in response to various stresses, including heat shock in mouse cells. The interaction of TLS (translocated in liposarcoma with CBP/p300 was induced by ncRNAs that bind to TLS, and this in turn results in inhibition of CBP/p300 histone acetyltransferase (HAT activity in human cells. Transcription regulator EWS (Ewing's sarcoma, which is highly related to TLS, and TLS specifically bind to G-quadruplex structures in vitro. The carboxy terminus containing the Arg-Gly-Gly (RGG repeat domains in these proteins are necessary for cis-repression of transcription activation and HAT activity by the N-terminal glutamine-rich domain. Especially, the RGG domain in the carboxy terminus of EWS is important for the G-quadruplex specific binding. Together, these data suggest that functions of EWS and TLS are modulated by specific structures of ncRNAs.

  14. Novel Functions for TAF7, a Regulator of TAF1-independent Transcription

    OpenAIRE

    Devaiah, Ballachanda N.; Lu, Hanxin; Gegonne, Anne; Sercan, Zeynep; Zhang, Hongen; Clifford, Robert J.; Lee, Maxwell P.; Singer, Dinah S.

    2010-01-01

    The transcription factor TFIID components TAF7 and TAF1 regulate eukaryotic transcription initiation. TAF7 regulates transcription initiation of TAF1-dependent genes by binding to the acetyltransferase (AT) domain of TAF1 and inhibiting the enzymatic activity that is essential for transcription. TAF7 is released from the TAF1-TFIID complex upon completion of preinitiation complex assembly, allowing transcription to initiate. However, not all transcription is TAF1-dependent, and the role of TA...

  15. Tectonic geomorphology and volcano-tectonic interaction in the eastern boundary of the Southern Cascades (Hat Creek Graben region, California, USA

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    Engielle Mae Raot-raot Paguican

    2016-07-01

    Full Text Available The eastern boundary of the Southern Cascades (Hat Creek Graben region, California, USA, is an extensively faulted volcanic corridor between the Cascade Range and Modoc Plateau. The east-west extending region is in the transition zone between the convergence and subduction of the Gorda Plate underneath the North American Plate; north-south shortening within the Klamath Mountain region; and transcurrent movement in the Walker Lane. We describe the geomorphological and tectonic features, their alignment and distribution, in order to understand the tectonic geomorphology and volcano-tectonic relationships. One outcome of the work is a more refined morpho-structural description that will affect future hazard assessment in the area.A database of volcanic centers and structures was created from interpretations of topographic models generated from satellite images. Volcanic centers in the region were classified by morphological type into cones, sub-cones, shields and massifs. A second classification by height separated the bigger and smaller edifices and revealed an evolutionary trend. Poisson Nearest Neighbor analysis shows that bigger volcanoes are spatially dispersed while smaller ones are clustered. Using volcano centroid locations, about 90 lineaments consisting of at least three centers within 6km of one another were found, revealing that preferential north-northwest directed pathways control the transport of magma from the source to the surface, consistent with the strikes of the major fault systems. Most of the volcano crater openings are perpendicular to the maximum horizontal stress, expected for extensional environments with dominant normal regional faults. These results imply that the extension of the Hat Creek Graben region and impingement of the Walker Lane is accommodated mostly by extensional faults and partly by the intrusions that formed the volcanoes. Early in the history of a volcano or volcano cluster, melt produced at depth in the

  16. 31P nuclear magnetic resonance spectroscopy studies of tumor energy metabolism and its relationship to intracapillary oxyhemoglobin saturation status and tumor hypoxia.

    Science.gov (United States)

    Rofstad, E K; DeMuth, P; Fenton, B M; Sutherland, R M

    1988-10-01

    Relationships between tumor bioenergetic status on the one hand and intracapillary oxyhemoglobin (HbO2) saturation status and fraction of radiobiologically hypoxic cells on the other were studied using two murine sarcoma lines (KHT, RIF-1) and two human ovarian carcinoma xenograft lines (MLS, OWI). Tumor energy metabolism was studied in vivo by 31P nuclear magnetic resonance (NMR) spectroscopy and the resonance area ratio (PCr + NTP beta)/Pi was used as parameter for bioenergetic status. Intracapillary HbO2 saturation status reflects the oxygen supply conditions in tumors and was measured in vitro using a cryospectrophotometric method. The KHT, RIF-1, and MLS lines showed decreasing bioenergetic status, i.e., decreasing PCr and NTP beta resonances and an increasing Pi resonance, with increasing tumor volume, whereas the OWI line showed no changes in these resonances during tumor growth. The volume-dependence of the HbO2 saturation status differed similarly among the tumor lines; HbO2 saturation status decreased with increasing tumor volume for the KHT, RIF-1, and MLS lines and was independent of tumor volume for the OWI line. Moreover, linear correlations were found between bioenergetic status and HbO2 saturation status for individual tumors of the KHT, RIF-1, and MLS lines. These observations together indicated a direct relationship between 31P-NMR spectral parameters and tumor oxygen supply conditions. However, this relationship was not identical for the different tumor lines, suggesting that it was influenced by intrinsic properties of the tumor cells such as rate of respiration and ability to survive under hypoxia. Similarly, there was no correlation between bioenergetic status and fraction of radiobiologically hypoxic cells across the four tumor lines. This indicates that 31P-NMR spectroscopy data have to be supplemented with other data, e.g., rate of oxygen consumption, cell survival time under hypoxic stress, and/or fraction of metabolically active

  17. Research report: the effects of hyperbaric oxygen preconditioning on myocardial biomarkers of cardioprotection in patients having coronary artery bypass graft surgery.

    Science.gov (United States)

    Jeysen, Zivan Yogaratnam; Gerard, Laden; Levant, Guvendik; Cowen, Mike; Cale, Alex; Griffin, Steve

    2011-01-01

    We have previously conducted and reported on the primary endpoint of a clinical study which demonstrated that hyperbaric oxygen (HBO2) preconditioning consisting of two 30-minute intervals of 100% oxygen at 2.4 atmospheres absolute (ATA) prior to coronary artery bypass graft (CABG) surgery leads to an improvement in left ventricular stroke work (LVSW) 24 hours following CABG. In that study, 81 patients were randomized to treatment with HBO2 (HBO2; n = 41) or routine treatment (Control Group; n = 40) prior to surgery. The objective of this manuscript is to further report on the result of the exploratory secondary endpoints from that study, specifically the effects of HBO2 preconditioning on biomarkers of myocardial protection. Intraoperative right atrial biopsies were assessed, via an Enzyme Linked ImmunoSorbent Assay (ELISA), for the expression of eNOS and HSP72. In this study, no significant differences were observed between the groups with respect to the quantity of myocardial eNOS and HSP72. However, in the HBO2 Group, following ischemia and reperfusion, the quantities of myocardial eNOS and HSP72 were increased. This suggests that HBO2 preconditioning in this group of patients may be capable of inducing endogenous cardioprotection following ischemic reperfusion injury (IRI).

  18. Variability in hyperbaric oxygen treatment for acute carbon monoxide poisoning.

    Science.gov (United States)

    Byrne, Brendan T; Lu, Jenny J; Valento, Matthew; Bryant, Sean M

    2012-01-01

    In patients with acute carbon monoxide (CO) poisoning, we have noted wide clinical variability in both criteria for hyperbaric oxygen (HBO2) treatment as well as HBO2 treatment regimens. Our aim was to survey Midwest hyperbaric centers for insight into specific criteria and protocols for treating acute CO toxicity with HBO2. Hyperbaric centers were identified from the published list of the Undersea and Hyperbaric Medical Society. Ninety-three centers from nine Midwestern states were contacted via telephone. A standard script was used to minimize surveyor bias. Thirty centers that treat CO poisonings were identified. One did not participate in the study. Nineteen reported a specific level of carboxyhemoglobin (COHb) that served as an independent indication for initiation of HBO2 treatment. Four centers used the COHb level as the exclusive indication for HBO2 treatment. Ten centers relied solely on reported symptoms, while the remaining centers used a combination of symptoms plus COHb levels. There were 19 separate treatment protocols. No uniform practice for either the initiation or implementation of HBO2 therapy for CO poisoning exists among U.S. Midwest hyperbaric centers responding to a survey. We see opportunity for specific targeted educational programs as well as further study.

  19. A novel method to quantify the activity of alcohol acetyltransferase Using a SnO2-based sensor of electronic nose.

    Science.gov (United States)

    Hu, Zhongqiu; Li, Xiaojing; Wang, Huxuan; Niu, Chen; Yuan, Yahong; Yue, Tianli

    2016-07-15

    Alcohol acetyltransferase (AATFase) extensively catalyzes the reactions of alcohols to acetic esters in microorganisms and plants. In this work, a novel method has been proposed to quantify the activity of AATFase using a SnO2-based sensor of electronic nose, which was determined on the basis of its higher sensitivity to the reducing alcohol than the oxidizing ester. The maximum value of the first-derivative of the signals from the SnO2-based sensor was therein found to be an eigenvalue of isoamyl alcohol concentration. Quadratic polynomial regression perfectly fitted the correlation between the eigenvalue and the isoamyl alcohol concentration. The method was used to determine the AATFase activity in this type of reaction by calculating the conversion rate of isoamyl alcohol. The proposed method has been successfully applied to determine the AATFase activity of a cider yeast strain. Compared with GC-MS, the method shows promises with ideal recovery and low cost. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Substrate-Induced Allosteric Change in the Quaternary Structure of the Spermidine N-Acetyltransferase SpeG.

    Science.gov (United States)

    Filippova, Ekaterina V; Weigand, Steven; Osipiuk, Jerzy; Kiryukhina, Olga; Joachimiak, Andrzej; Anderson, Wayne F

    2015-11-06

    The spermidine N-acetyltransferase SpeG is a dodecameric enzyme that catalyzes the transfer of an acetyl group from acetyl coenzyme A to polyamines such as spermidine and spermine. SpeG has an allosteric polyamine-binding site and acetylating polyamines regulate their intracellular concentrations. The structures of SpeG from Vibrio cholerae in complexes with polyamines and cofactor have been characterized earlier. Here, we present the dodecameric structure of SpeG from V. cholerae in a ligand-free form in three different conformational states: open, intermediate and closed. All structures were crystallized in C2 space group symmetry and contain six monomers in the asymmetric unit cell. Two hexamers related by crystallographic 2-fold symmetry form the SpeG dodecamer. The open and intermediate states have a unique open dodecameric ring. This SpeG dodecamer is asymmetric except for the one 2-fold axis and is unlike any known dodecameric structure. Using a fluorescence thermal shift assay, size-exclusion chromatography with multi-angle light scattering, small-angle X-ray scattering analysis, negative-stain electron microscopy and structural analysis, we demonstrate that this unique open dodecameric state exists in solution. Our combined results indicate that polyamines trigger conformational changes and induce the symmetric closed dodecameric state of the protein when they bind to their allosteric sites. Copyright © 2015. Published by Elsevier Ltd.