WorldWideScience

Sample records for hp1a positively regulates

  1. Heterochromatin protein 1 (HP1a positively regulates euchromatic gene expression through RNA transcript association and interaction with hnRNPs in Drosophila.

    Directory of Open Access Journals (Sweden)

    Lucia Piacentini

    2009-10-01

    Full Text Available Heterochromatin Protein 1 (HP1a is a well-known conserved protein involved in heterochromatin formation and gene silencing in different species including humans. A general model has been proposed for heterochromatin formation and epigenetic gene silencing in different species that implies an essential role for HP1a. According to the model, histone methyltransferase enzymes (HMTases methylate the histone H3 at lysine 9 (H3K9me, creating selective binding sites for itself and the chromodomain of HP1a. This complex is thought to form a higher order chromatin state that represses gene activity. It has also been found that HP1a plays a role in telomere capping. Surprisingly, recent studies have shown that HP1a is present at many euchromatic sites along polytene chromosomes of Drosophila melanogaster, including the developmental and heat-shock-induced puffs, and that this protein can be removed from these sites by in vivo RNase treatment, thus suggesting an association of HP1a with the transcripts of many active genes. To test this suggestion, we performed an extensive screening by RIP-chip assay (RNA-immunoprecipitation on microarrays, and we found that HP1a is associated with transcripts of more than one hundred euchromatic genes. An expression analysis in HP1a mutants shows that HP1a is required for positive regulation of these genes. Cytogenetic and molecular assays show that HP1a also interacts with the well known proteins DDP1, HRB87F, and PEP, which belong to different classes of heterogeneous nuclear ribonucleoproteins (hnRNPs involved in RNA processing. Surprisingly, we found that all these hnRNP proteins also bind heterochromatin and are dominant suppressors of position effect variegation. Together, our data show novel and unexpected functions for HP1a and hnRNPs proteins. All these proteins are in fact involved both in RNA transcript processing and in heterochromatin formation. This suggests that, in general, similar epigenetic mechanisms

  2. Analysis of HP1α regulation in human breast cancer cells

    DEFF Research Database (Denmark)

    Thomsen, Rune; Christensen, Dennis B; Rosborg, Sanne

    2011-01-01

    The three mammalian HP1 proteins, HP1α/CBX5, HP1β/CBX1, and HPγ/CBX3, are involved in chromatin packing and gene regulation. The HP1α protein is down-regulated in invasive compared to non-invasive breast cancer cells and HP1α is a suppressor of cell migration and invasion. In this report, we...... examined the background for HP1α protein down-regulation in invasive breast cancer cells. We identified a strict correlation between HP1α down-regulation at the protein level and the mRNA level. The HP1α mRNA down-regulation in invasive cancer cells was not caused by mRNA destabilization. Chromatin...... immunoprecipitation analysis of the HP1α gene showed a decrease in the histone mark for transcriptional activity H3-K36 tri-methylation and RNA polymerase II in invasive breast cancer cells which correlated with a decreased abundance of basal transcription factors at the HP1α promoter. E2F transcription factors...

  3. The Aurora A-HP1γ pathway regulates gene expression and mitosis in cells from the sperm lineage.

    Science.gov (United States)

    Leonard, Phoebe H; Grzenda, Adrienne; Mathison, Angela; Morbeck, Dean E; Fredrickson, Jolene R; de Assuncao, Thiago M; Christensen, Trace; Salisbury, Jeffrey; Calvo, Ezequiel; Iovanna, Juan; Coddington, Charles C; Urrutia, Raul; Lomberk, Gwen

    2015-05-29

    HP1γ, a well-known regulator of gene expression, has been recently identified to be a target of Aurora A, a mitotic kinase which is important for both gametogenesis and embryogenesis. The purpose of this study was to define whether the Aurora A-HP1γ pathway supports cell division of gametes and/or early embryos, using western blot, immunofluorescence, immunohistochemistry, electron microscopy, shRNA-based knockdown, site-directed mutagenesis, and Affymetrix-based genome-wide expression profiles. We find that the form of HP1γ phosphorylated by Aurora A, P-Ser83 HP1γ, is a passenger protein, which localizes to the spermatozoa centriole and axoneme. In addition, disruption in this pathway causes centrosomal abnormalities and aberrations in cell division. Expression profiling of male germ cell lines demonstrates that HP1γ phosphorylation is critical for the regulation of mitosis-associated gene expression networks. In female gametes, we observe that P-Ser83-HP1γ is not present in meiotic centrosomes of M2 oocytes, but after syngamy, it becomes detectable during cleavage divisions, coinciding with early embryonic genome activation. These results support the idea that phosphorylation of HP1γ by Aurora A plays a role in the regulation of gene expression and mitotic cell division in cells from the sperm lineage and in early embryos. Combined, this data is relevant to better understanding the function of HP1γ in reproductive biology.

  4. Interaction of HP1 and Brg1/Brm with the globular domain of histone H3 is required for HP1-mediated repression.

    Directory of Open Access Journals (Sweden)

    Marc Lavigne

    2009-12-01

    Full Text Available The heterochromatin-enriched HP1 proteins play a critical role in regulation of transcription. These proteins contain two related domains known as the chromo- and the chromoshadow-domain. The chromo-domain binds histone H3 tails methylated on lysine 9. However, in vivo and in vitro experiments have shown that the affinity of HP1 proteins to native methylated chromatin is relatively poor and that the opening of chromatin occurring during DNA replication facilitates their binding to nucleosomes. These observations prompted us to investigate whether HP1 proteins have additional histone binding activities, envisioning also affinity for regions potentially occluded by the nucleosome structure. We find that the chromoshadow-domain interacts with histone H3 in a region located partially inside the nucleosomal barrel at the entry/exit point of the nucleosome. Interestingly, this region is also contacted by the catalytic subunits of the human SWI/SNF complex. In vitro, efficient SWI/SNF remodeling requires this contact and is inhibited in the presence of HP1 proteins. The antagonism between SWI/SNF and HP1 proteins is also observed in vivo on a series of interferon-regulated genes. Finally, we show that SWI/SNF activity favors loading of HP1 proteins to chromatin both in vivo and in vitro. Altogether, our data suggest that HP1 chromoshadow-domains can benefit from the opening of nucleosomal structures to bind chromatin and that HP1 proteins use this property to detect and arrest unwanted chromatin remodeling.

  5. Enrichment of HP1a on Drosophila chromosome 4 genes creates an alternate chromatin structure critical for regulation in this heterochromatic domain.

    Directory of Open Access Journals (Sweden)

    Nicole C Riddle

    2012-09-01

    Full Text Available Chromatin environments differ greatly within a eukaryotic genome, depending on expression state, chromosomal location, and nuclear position. In genomic regions characterized by high repeat content and high gene density, chromatin structure must silence transposable elements but permit expression of embedded genes. We have investigated one such region, chromosome 4 of Drosophila melanogaster. Using chromatin-immunoprecipitation followed by microarray (ChIP-chip analysis, we examined enrichment patterns of 20 histone modifications and 25 chromosomal proteins in S2 and BG3 cells, as well as the changes in several marks resulting from mutations in key proteins. Active genes on chromosome 4 are distinct from those in euchromatin or pericentric heterochromatin: while there is a depletion of silencing marks at the transcription start sites (TSSs, HP1a and H3K9me3, but not H3K9me2, are enriched strongly over gene bodies. Intriguingly, genes on chromosome 4 are less frequently associated with paused polymerase. However, when the chromatin is altered by depleting HP1a or POF, the RNA pol II enrichment patterns of many chromosome 4 genes shift, showing a significant decrease over gene bodies but not at TSSs, accompanied by lower expression of those genes. Chromosome 4 genes have a low incidence of TRL/GAGA factor binding sites and a low T(m downstream of the TSS, characteristics that could contribute to a low incidence of RNA polymerase pausing. Our data also indicate that EGG and POF jointly regulate H3K9 methylation and promote HP1a binding over gene bodies, while HP1a targeting and H3K9 methylation are maintained at the repeats by an independent mechanism. The HP1a-enriched, POF-associated chromatin structure over the gene bodies may represent one type of adaptation for genes embedded in repetitive DNA.

  6. dAdd1 and dXNP prevent genome instability by maintaining HP1a localization at Drosophila telomeres.

    Science.gov (United States)

    Chavez, Joselyn; Murillo-Maldonado, Juan Manuel; Bahena, Vanessa; Cruz, Ana Karina; Castañeda-Sortibrán, América; Rodriguez-Arnaiz, Rosario; Zurita, Mario; Valadez-Graham, Viviana

    2017-12-01

    Telomeres are important contributors to genome stability, as they prevent linear chromosome end degradation and contribute to the avoidance of telomeric fusions. An important component of the telomeres is the heterochromatin protein 1a (HP1a). Mutations in Su(var)205, the gene encoding HP1a in Drosophila, result in telomeric fusions, retrotransposon regulation loss and larger telomeres, leading to chromosome instability. Previously, it was found that several proteins physically interact with HP1a, including dXNP and dAdd1 (orthologues to the mammalian ATRX gene). In this study, we found that mutations in the genes encoding the dXNP and dAdd1 proteins affect chromosome stability, causing chromosomal aberrations, including telomeric defects, similar to those observed in Su(var)205 mutants. In somatic cells, we observed that dXNP and dAdd1 participate in the silencing of the telomeric HTT array of retrotransposons, preventing anomalous retrotransposon transcription and integration. Furthermore, the lack of dAdd1 results in the loss of HP1a from the telomeric regions without affecting other chromosomal HP1a binding sites; mutations in dxnp also affected HP1a localization but not at all telomeres, suggesting a specialized role for dAdd1 and dXNP proteins in locating HP1a at the tips of the chromosomes. These results place dAdd1 as an essential regulator of HP1a localization and function in the telomere heterochromatic domain.

  7. Drosophila atm/telomere fusion is required for telomeric localization of HP1 and telomere position effect.

    Science.gov (United States)

    Oikemus, Sarah R; McGinnis, Nadine; Queiroz-Machado, Joana; Tukachinsky, Hanna; Takada, Saeko; Sunkel, Claudio E; Brodsky, Michael H

    2004-08-01

    Terminal deletions of Drosophila chromosomes can be stably protected from end-to-end fusion despite the absence of all telomere-associated sequences. The sequence-independent protection of these telomeres suggests that recognition of chromosome ends might contribute to the epigenetic protection of telomeres. In mammals, Ataxia Telangiectasia Mutated (ATM) is activated by DNA damage and acts through an unknown, telomerase-independent mechanism to regulate telomere length and protection. We demonstrate that the Drosophila homolog of ATM is encoded by the telomere fusion (tefu) gene. In the absence of ATM, telomere fusions occur even though telomere-specific Het-A sequences are still present. High levels of spontaneous apoptosis are observed in ATM-deficient tissues, indicating that telomere dysfunction induces apoptosis in Drosophila. Suppression of this apoptosis by p53 mutations suggests that loss of ATM activates apoptosis through a DNA damage-response mechanism. Loss of ATM reduces the levels of heterochromatin protein 1 (HP1) at telomeres and suppresses telomere position effect. We propose that recognition of chromosome ends by ATM prevents telomere fusion and apoptosis by recruiting chromatin-modifying complexes to telomeres.

  8. Identification and characterization of a nuclear localization signal of TRIM28 that overlaps with the HP1 box

    International Nuclear Information System (INIS)

    Moriyama, Tetsuji; Sangel, Percival; Yamaguchi, Hiroki; Obuse, Chikashi; Miyamoto, Yoichi; Oka, Masahiro; Yoneda, Yoshihiro

    2015-01-01

    Tripartite motif-containing 28 (TRIM28) is a transcription regulator, which forms a repressor complex containing heterochromatin protein 1 (HP1). Here, we report identification of a nuclear localization signal (NLS) within the 462-494 amino acid region of TRIM28 that overlaps with its HP1 binding site, HP1 box. GST-pulldown experiments revealed the interaction of the arginine-rich TRIM28 NLS with various importin α subtypes (α1, α2 and α4). In vitro transport assay demonstrated that nuclear localization of GFP-TRIM28 NLS is mediated by importin αs, in conjunction with importin β1 and Ran. Further, we demonstrated that HP1 and importin αs compete for binding to TRIM28. Together, our findings suggest that importin α has an essential role in the nuclear delivery and preferential HP1 interaction of TRIM28. - Highlights: • TRIM28 contains an NLS within the 462-494 amino acid region. • The nuclear import of TRIM28 is mediated by importin α/importin β1. • TRIM28 NLS overlaps with HP1 Box. • HP1 and importin α compete for binding to TRIM28

  9. Identification and characterization of a nuclear localization signal of TRIM28 that overlaps with the HP1 box

    Energy Technology Data Exchange (ETDEWEB)

    Moriyama, Tetsuji; Sangel, Percival [Laboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka 567-0085 (Japan); Yamaguchi, Hiroki [School of Medicine, Osaka University, Osaka 565-0871 (Japan); Obuse, Chikashi [Graduate School of Life Science, Hokkaido University, Sapporo 001-0021 (Japan); Miyamoto, Yoichi [Laboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka 567-0085 (Japan); Oka, Masahiro, E-mail: moka@nibiohn.go.jp [Laboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka 567-0085 (Japan); Laboratory of Biomedical Innovation, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871 (Japan); Yoneda, Yoshihiro, E-mail: y-yoneda@nibiohn.go.jp [National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka 567-0085 (Japan); Laboratory of Biomedical Innovation, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871 (Japan)

    2015-07-03

    Tripartite motif-containing 28 (TRIM28) is a transcription regulator, which forms a repressor complex containing heterochromatin protein 1 (HP1). Here, we report identification of a nuclear localization signal (NLS) within the 462-494 amino acid region of TRIM28 that overlaps with its HP1 binding site, HP1 box. GST-pulldown experiments revealed the interaction of the arginine-rich TRIM28 NLS with various importin α subtypes (α1, α2 and α4). In vitro transport assay demonstrated that nuclear localization of GFP-TRIM28 NLS is mediated by importin αs, in conjunction with importin β1 and Ran. Further, we demonstrated that HP1 and importin αs compete for binding to TRIM28. Together, our findings suggest that importin α has an essential role in the nuclear delivery and preferential HP1 interaction of TRIM28. - Highlights: • TRIM28 contains an NLS within the 462-494 amino acid region. • The nuclear import of TRIM28 is mediated by importin α/importin β1. • TRIM28 NLS overlaps with HP1 Box. • HP1 and importin α compete for binding to TRIM28.

  10. HP1γ function is required for male germ cell survival and spermatogenesis

    Directory of Open Access Journals (Sweden)

    Brown Jeremy P

    2010-04-01

    Full Text Available Abstract Background HP1 proteins are conserved components of eukaryotic constitutive heterochromatin. In mammals, there are three genes that encode HP1-like proteins, termed HP1α, HP1β and HP1γ, which have a high degree of homology This paper describes for the first time, to our knowledge, the physiological function of HP1γ using a gene-targeted mouse. Results While targeting the Cbx3 gene (encoding the HP1γ protein with a conditional targeting vector, we generated a hypomorphic allele (Cbx3hypo, which resulted in much reduced (barely detectable levels of HP1γ protein. Homozygotes for the hypomorphic allele (Cbx3hypo/hypo are rare, with only 1% of Cbx3hypo/hypo animals reaching adulthood. Adult males exhibit a severe hypogonadism that is associated with a loss of germ cells, with some seminiferous tubules retaining only the supporting Sertoli cells (Sertoli cell-only phenotype. The percentage of seminiferous tubules that are positive for L1 ORF1 protein (ORF1p in Cbx3hypo/hypo testes is greater than that for wild-type testes, indicating that L1 retrotransposon silencing is reversed, leading to ectopic expression of ORF1p in Cbx3hypo/hypo germ cells. Conclusions The Cbx3 gene product (the HP1γ protein has a non-redundant function during spermatogenesis that cannot be compensated for by the other two HP1 isotypes. The Cbx3hypo/hypo spermatogenesis defect is similar to that found in Miwi2 and Dnmt3L mutants. The Cbx3 gene-targeted mice generated in this study provide an appropriate model for the study of HP1γ in transposon silencing and parental imprinting.

  11. Proportionate Dwarfism in Mice Lacking Heterochromatin Protein 1 Binding Protein 3 (HP1BP3) Is Associated With Alterations in the Endocrine IGF-1 Pathway.

    Science.gov (United States)

    Garfinkel, Benjamin P; Arad, Shiri; Le, Phuong T; Bustin, Michael; Rosen, Clifford J; Gabet, Yankel; Orly, Joseph

    2015-12-01

    Heterochromatin protein 1 binding protein 3 (HP1BP3) is a recently described histone H1-related protein with roles in chromatin structure and transcriptional regulation. To explore the potential physiological role of HP1BP3, we have previously described an Hp1bp3(-/-) mouse model with reduced postnatal viability and growth. We now find that these mice are proportionate dwarfs, with reduction in body weight, body length, and organ weight. In addition to their small size, microcomputed tomography analysis showed that Hp1bp3(-/-) mice present a dramatic impairment of their bone development and structure. By 3 weeks of age, mice of both sexes have severely impaired cortical and trabecular bone, and these defects persist into adulthood and beyond. Primary cultures of both osteoblasts and osteoclasts from Hp1bp3(-/-) bone marrow and splenocytes, respectively, showed normal differentiation and function, strongly suggesting that the impaired bone accrual is due to noncell autonomous systemic cues in vivo. One major endocrine pathway regulating both body growth and bone acquisition is the IGF regulatory system, composed of IGF-1, the IGF receptors, and the IGF-binding proteins (IGFBPs). At 3 weeks of age, Hp1bp3(-/-) mice exhibited a 60% reduction in circulating IGF-1 and a 4-fold increase in the levels of IGFBP-1 and IGFBP-2. These alterations were reflected in similar changes in the hepatic transcripts of the Igf1, Igfbp1, and Igfbp2 genes. Collectively, these results suggest that HP1BP3 plays a key role in normal growth and bone development by regulating transcription of endocrine IGF-1 components.

  12. KDM2A integrates DNA and histone modification signals through a CXXC/PHD module and direct interaction with HP1

    Science.gov (United States)

    Borgel, Julie; Tyl, Marek; Schiller, Karin; Pusztai, Zsofia; Dooley, Christopher M.; Deng, Wen; Wooding, Carol; White, Richard J.; Warnecke, Tobias; Leonhardt, Heinrich; Busch-Nentwich, Elisabeth M.

    2017-01-01

    Abstract Functional genomic elements are marked by characteristic DNA and histone modification signatures. How combinatorial chromatin modification states are recognized by epigenetic reader proteins and how this is linked to their biological function is largely unknown. Here we provide a detailed molecular analysis of chromatin recognition by the lysine demethylase KDM2A. Using biochemical approaches we identify a nucleosome interaction module within KDM2A consisting of a CXXC type zinc finger, a PHD domain and a newly identified Heterochromatin Protein 1 (HP1) interaction motif that mediates direct binding between KDM2A and HP1. This nucleosome interaction module enables KDM2A to decode nucleosomal H3K9me3 modification in addition to CpG methylation signals. The multivalent engagement with DNA and HP1 results in a nucleosome binding circuit in which KDM2A can be recruited to H3K9me3-modified chromatin through HP1, and HP1 can be recruited to unmodified chromatin by KDM2A. A KDM2A mutant deficient in HP1-binding is inactive in an in vivo overexpression assay in zebrafish embryos demonstrating that the HP1 interaction is essential for KDM2A function. Our results reveal a complex regulation of chromatin binding for both KDM2A and HP1 that is modulated by DNA- and H3K9-methylation, and suggest a direct role for KDM2A in chromatin silencing. PMID:28180290

  13. Proportionate Dwarfism in Mice Lacking Heterochromatin Protein 1 Binding Protein 3 (HP1BP3) Is Associated With Alterations in the Endocrine IGF-1 Pathway

    OpenAIRE

    Garfinkel, Benjamin P.; Arad, Shiri; Le, Phuong T.; Bustin, Michael; Rosen, Clifford J.; Gabet, Yankel; Orly, Joseph

    2015-01-01

    Heterochromatin protein 1 binding protein 3 (HP1BP3) is a recently described histone H1-related protein with roles in chromatin structure and transcriptional regulation. To explore the potential physiological role of HP1BP3, we have previously described an Hp1bp3?/? mouse model with reduced postnatal viability and growth. We now find that these mice are proportionate dwarfs, with reduction in body weight, body length, and organ weight. In addition to their small size, microcomputed tomography...

  14. Urinary 1-hydroxypyrene (1-HP) in environmental and occupational studies--a review

    DEFF Research Database (Denmark)

    Hansen, Ase M; Mathiesen, Line; Pedersen, Marie

    2008-01-01

    , volume (and time) or concentrations of creatinine are often used to standardize for diuresis. To be able to compare the included studies we recalculated the given concentrations to mumol 1-HP/mol creatinine. In conclusion, the highest concentrations of urinary 1-HP are found among workers...

  15. Celiac disease and Hp infection association in Iran Enfermedades celiacas e infección por Hp en Irán

    Directory of Open Access Journals (Sweden)

    M. Rostami-Nejad

    2009-12-01

    Full Text Available Background: we assessed the prevalence, the related symptoms, and the endoscopic and histologic gastric features of celiac disease (CD in patients with Helicobacter pylori (Hp. Methods: 450 dyspeptic patients were studied. Biopsies of gastric antrum and duodenum, CD serology, and total IgA were obtained. Histological findings were scored with the Marsh-Rostami criteria. Results: 411 (91.3% patients were Hp positive. Duodenal histology was normal in 385 (85.6% patients, 124 (27.5% had duodenitis and 28 (6.2% showed duodenal abnormalities (Marsh I-IIIc. Twenty three/28 (82.1% patients with malabsorption pattern were also Hp positive. Serological analysis: 12 of 31 (38.7% positive patients had abnormal histology (Marsh I,-IIIc. Nine out 450 patients were IgA deficient; none of them was serologically positive for CD. Conclusion: although a high prevalence of Hp infection was found in this study, the relationship between Hp infection and CD was similar to that reported in other geographic areas.

  16. Notes on HP1 a software package for simulating variably-saturated water flow, heat transport, solute transport, and biogeochemistry in porous media. HP1 Version 2.2

    Energy Technology Data Exchange (ETDEWEB)

    Jacques, D.; Simunek, J.

    2010-01-15

    HP1 is a comprehensive modeling tool in terms of processes and reactions for simulating reactive transport and biogeochemical processes in variably-saturated porous media. HP1 results from coupling the water and solute transport model HYDRUS-1D (Simunek et al., 2009a) and PHREEQC-2 (Parkhurst and Appelo, 1999). This note provides an overview of how to set up and execute a HP1 project using version 2.2.002 of HP1 and version 4.13 of the graphical user interface (GUI) of HYDRUS-1D. A large part of this note are step-by-step instructions for selected examples involving mineral dissolution and precipitation, cation exchange, surface complexation and kinetic degradation networks. The implementation of variably-saturated flow conditions, changing boundary conditions, a layered soil profile or immobile water is also illustrated.

  17. Notes on HP1 a software package for simulating variably-saturated water flow, heat transport, solute transport, and biogeochemistry in porous media. HP1 Version 2.2

    International Nuclear Information System (INIS)

    Jacques, D.; Simunek, J.

    2010-01-01

    HP1 is a comprehensive modeling tool in terms of processes and reactions for simulating reactive transport and biogeochemical processes in variably-saturated porous media. HP1 results from coupling the water and solute transport model HYDRUS-1D (Simunek et al., 2009a) and PHREEQC-2 (Parkhurst and Appelo, 1999). This note provides an overview of how to set up and execute a HP1 project using version 2.2.002 of HP1 and version 4.13 of the graphical user interface (GUI) of HYDRUS-1D. A large part of this note are step-by-step instructions for selected examples involving mineral dissolution and precipitation, cation exchange, surface complexation and kinetic degradation networks. The implementation of variably-saturated flow conditions, changing boundary conditions, a layered soil profile or immobile water is also illustrated.

  18. Epigenetic regulation of facultative heterochromatinisation in Planococcus citri via the Me(3)K9H3-HP1-Me(3)K20H4 pathway.

    Science.gov (United States)

    Bongiorni, Silvia; Pasqualini, Barbara; Taranta, Monia; Singh, Prim B; Prantera, Giorgio

    2007-03-15

    Using RNA interference (RNAi) we have conducted a functional analysis of the HP1-like chromobox gene pchet2 during embryogenesis of the mealybug Planococcus citri. Knocking down pchet2 expression results in decondensation of the male-specific chromocenter that normally arises from the developmentally-regulated facultative heterochromatinisation of the paternal chromosome complement. Together with the disappearance of the chromocenter the staining levels of two associated histone modifications, tri-methylated lysine 9 of histone H3 [Me(3)K9H3] and tri-methylated lysine 20 of histone H4 [Me(3)K20H4], are reduced to undetectable levels. Embryos treated with double-stranded RNA (dsRNA) targeting pchet2 also exhibit chromosome abnormalities, such as aberrant chromosome condensation, and also the presence of metaphases that contain 'lagging' chromosomes. We conclude that PCHET2 regulates chromosome behavior during metaphase and is a crucial component of a Me(3)K9H3-HP1-Me(3)K20H4 pathway involved in the facultative heterochromatinisation of the (imprinted) paternal chromosome set.

  19. High-resolution mapping reveals links of HP1 with active and inactive chromatin components.

    Directory of Open Access Journals (Sweden)

    Elzo de Wit

    2007-03-01

    Full Text Available Heterochromatin protein 1 (HP1 is commonly seen as a key factor of repressive heterochromatin, even though a few genes are known to require HP1-chromatin for their expression. To obtain insight into the targeting of HP1 and its interplay with other chromatin components, we have mapped HP1-binding sites on Chromosomes 2 and 4 in Drosophila Kc cells using high-density oligonucleotide arrays and the DNA adenine methyltransferase identification (DamID technique. The resulting high-resolution maps show that HP1 forms large domains in pericentric regions, but is targeted to single genes on chromosome arms. Intriguingly, HP1 shows a striking preference for exon-dense genes on chromosome arms. Furthermore, HP1 binds along entire transcription units, except for 5' regions. Comparison with expression data shows that most of these genes are actively transcribed. HP1 target genes are also marked by the histone variant H3.3 and dimethylated histone 3 lysine 4 (H3K4me2, which are both typical of active chromatin. Interestingly, H3.3 deposition, which is usually observed along entire transcription units, is limited to the 5' ends of HP1-bound genes. Thus, H3.3 and HP1 are mutually exclusive marks on active chromatin. Additionally, we observed that HP1-chromatin and Polycomb-chromatin are nonoverlapping, but often closely juxtaposed, suggesting an interplay between both types of chromatin. These results demonstrate that HP1-chromatin is transcriptionally active and has extensive links with several other chromatin components.

  20. Piezo type mechanosensitive ion channel component 1 functions as a regulator of the cell fate determination of mesenchymal stem cells.

    Science.gov (United States)

    Sugimoto, Asuna; Miyazaki, Aya; Kawarabayashi, Keita; Shono, Masayuki; Akazawa, Yuki; Hasegawa, Tomokazu; Ueda-Yamaguchi, Kimiko; Kitamura, Takamasa; Yoshizaki, Keigo; Fukumoto, Satoshi; Iwamoto, Tsutomu

    2017-12-18

    The extracellular environment regulates the dynamic behaviors of cells. However, the effects of hydrostatic pressure (HP) on cell fate determination of mesenchymal stem cells (MSCs) are not clearly understood. Here, we established a cell culture chamber to control HP. Using this system, we found that the promotion of osteogenic differentiation by HP is depend on bone morphogenetic protein 2 (BMP2) expression regulated by Piezo type mechanosensitive ion channel component 1 (PIEZO1) in MSCs. The PIEZO1 was expressed and induced after HP loading in primary MSCs and MSC lines, UE7T-13 and SDP11. HP and Yoda1, an activator of PIEZO1, promoted BMP2 expression and osteoblast differentiation, whereas inhibits adipocyte differentiation. Conversely, PIEZO1 inhibition reduced osteoblast differentiation and BMP2 expression. Furthermore, Blocking of BMP2 function by noggin inhibits HP induced osteogenic maker genes expression. In addition, in an in vivo model of medaka with HP loading, HP promoted caudal fin ray development whereas inhibition of piezo1 using GsMTx4 suppressed its development. Thus, our results suggested that PIEZO1 is responsible for HP and could functions as a factor for cell fate determination of MSCs by regulating BMP2 expression.

  1. Analysis of the human HP1 interactome reveals novel binding partners

    DEFF Research Database (Denmark)

    Rosnoblet, Claire; Vandamme, Julien; Völkel, Pamela

    2011-01-01

    Heterochromatin protein 1 (HP1) has first been described in Drosophila as an essential component of constitutive heterochromatin required for stable epigenetic gene silencing. Less is known about the three mammalian HP1 isotypes CBX1, CBX3 and CBX5. Here, we applied a tandem affinity purification...

  2. Pulmonary haptoglobin (pHp) is part of the surfactant system in the human lung.

    Science.gov (United States)

    Abdullah, Mahdi; Goldmann, Torsten

    2012-11-20

    Since the existence of pHp was demonstrated, it has been shown that this molecule and its receptor CD163 are regulated by different stimuli. Furthermore, a comparably fast secretion of pHp was described as well as the immuno-stimulatory effects. The intention of this study was to elucidate the role of pHp in the human lungs further. Here we show, by means of confocal microscopy and immune-electron-microscopy, a clear co-localization of pHp with surfactant protein-B in lamellar bodies of alveolar epithelial cells type II. These results are underlined by immunohistochemical stainings in differently fixed human lung tissues, which show pHp in vesicular and released form. The images of the released form resemble the intended position of surfactant in the human alveolus. pHp is secreted by Alveolar epithelial cells type II as previously shown. Moreover, pHp is co-localized with Surfactant protein-B. We conclude that the presented data shows that pHp is a native part of the surfactant system in the human lung. http://www.diagnosticpathology.diagnomx.eu/vs/2563584738239912.

  3. Helicobacter pylori stool antigen test (HpSA) for the diagnosis of gastric infection

    International Nuclear Information System (INIS)

    Faruqui, A.N.; Majid, U.; Ahmed, L.; Khalil, M.; Hussan, M.U.

    2007-01-01

    To determine the accuracy of Helicobacter pylori Stool Antigen test (HpSA), compared with endoscopic histopathology for the diagnosis of gastric Helicobecter pylori infection. A total of 50 patients underwent endoscopy for gastric antral mucosal tissue biopsy for histopathology of H.pylori and advised for HpSA. Patient's information including age, gender, past history, presenting signs and symptoms, results of HpSA and histopathology were recorded. Sensitivity analysis was performed to calculate sensitivity, specificity, and predictive values of HpSA. Among 50 patients, 48% males and 52% females (M: F 1: 1.08), a total of 27 (54%) were true positive while 20 (40%) were true negative. Two patients were false negative and only one was false positive. Sensitivity of HpSA was, therefore, 93.1%, specificity 95% and positive and negative predictive values were 96.42% and 90.9% respectively. Helicobacter pylori stool antigen was an accurate and reliable test for the diagnosis of gastric H. pylori infection. (author)

  4. LMTK1 regulates dendritic formation by regulating movement of Rab11A-positive endosomes.

    Science.gov (United States)

    Takano, Tetsuya; Urushibara, Tomoki; Yoshioka, Nozomu; Saito, Taro; Fukuda, Mitsunori; Tomomura, Mineko; Hisanaga, Shin-Ichi

    2014-06-01

    Neurons extend two types of neurites-axons and dendrites-that differ in structure and function. Although it is well understood that the cytoskeleton plays a pivotal role in neurite differentiation and extension, the mechanisms by which membrane components are supplied to growing axons or dendrites is largely unknown. We previously reported that the membrane supply to axons is regulated by lemur kinase 1 (LMTK1) through Rab11A-positive endosomes. Here we investigate the role of LMTK1 in dendrite formation. Down-regulation of LMTK1 increases dendrite growth and branching of cerebral cortical neurons in vitro and in vivo. LMTK1 knockout significantly enhances the prevalence, velocity, and run length of anterograde movement of Rab11A-positive endosomes to levels similar to those expressing constitutively active Rab11A-Q70L. Rab11A-positive endosome dynamics also increases in the cell body and growth cone of LMTK1-deficient neurons. Moreover, a nonphosphorylatable LMTK1 mutant (Ser34Ala, a Cdk5 phosphorylation site) dramatically promotes dendrite growth. Thus LMTK1 negatively controls dendritic formation by regulating Rab11A-positive endosomal trafficking in a Cdk5-dependent manner, indicating the Cdk5-LMTK1-Rab11A pathway as a regulatory mechanism of dendrite development as well as axon outgrowth. © 2014 Takano et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  5. Helicobacter pylori protein HP0986 (TieA) interacts with mouse TNFR1 and triggers proinflammatory and proapoptotic signaling pathways in cultured macrophage cells (RAW 264.7).

    Science.gov (United States)

    Ansari, Suhail A; Devi, Savita; Tenguria, Shivendra; Kumar, Ashutosh; Ahmed, Niyaz

    2014-08-01

    HP0986 protein of Helicobacter pylori has been shown to trigger induction of proinflammatory cytokines (IL-8 and TNF-α) through the activation of NF-κB and also to induce Fas mediated apoptosis of human macrophage cells (THP-1). In this study, we unravel mechanistic details of the biological effects of this protein in a murine macrophage environment. Up regulation of MCP-1 and TNF-α in HP0986-induced RAW 264.7 cells occurred subsequent to the activation and translocation of NF-κB to the cell nucleus. Further, HP0986 induced apoptosis of RAW 264.7 cells through Fas activation and this was in agreement with previous observations made with THP-1 cells. Our studies indicated activation of TNFR1 through interaction with HP0986 and this elicited the aforementioned responses independent of TLR2, TLR4 or TNFR2. We found that mouse TNFR1 activation by HP0986 facilitates formation of a complex comprising of TNFR1, TRADD and TRAF2, and this occurs upstream of NF-κB activation. Furthermore, FADD also forms a second complex, at a later stage, together with TNFR1 and TRADD, resulting in caspase-8 activation and thereby the apoptosis of RAW 264.7 cells. In summary, our observations reveal finer details of the functional activity of HP0986 protein in relation to its behavior in a murine macrophage cell environment. These findings reconfirm the proinflammatory and apoptotic role of HP0986 signifying it to be an important trigger of innate responses. These observations form much needed baseline data entailing future in vivo studies of the functions of HP0986 in a murine model. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Haplotype association between haptoglobin (Hp2 and Hp promoter SNP (A-61C may explain previous controversy of haptoglobin and malaria protection.

    Directory of Open Access Journals (Sweden)

    Sharon E Cox

    2007-04-01

    Full Text Available Malaria is one of the strongest recent selective pressures on the human genome, as evidenced by the high levels of varying haemoglobinopathies in human populations-despite the increased risk of mortality in the homozygous states. Previously, functional polymorphisms of Hp, coded by the co-dominant alleles Hp1 and Hp2, have been variously associated with several infectious diseases, including malaria susceptibility.Risk of a clinical malarial episode over the course of a malarial transmission season was assessed using active surveillance in a cohort of Gambian children aged 10-72 months. We report for the first time that the major haplotype for the A-61C mutant allele in the promoter of haptoglobin (Hp-an acute phase protein that clears haemoglobin released from haemolysis of red cells-is associated with protection from malarial infection in older children, (children aged >or=36 months, >500 parasites/ul and temperature >37.5 degrees C; OR = 0.42; [95% CI 0.24-0.73] p = 0.002 (lr test for interaction, or=36 months, p = 0.014. Protection was also observed using two other definitions, including temperature >37.5 degrees C, dipstick positive, plus clinical judgement of malaria blinded to dipstick result (all ages, OR = 0.48, [95% CI 0.30-0.78] p = 0.003; >or=36 months, OR = 0.31, [95% CI 0.15-0.62] p = 0.001. A similar level of protection was observed for the known protective genetic variant, sickle cell trait (HbAS.We propose that previous conflicting results between Hp phenotypes/genotypes and malaria susceptibility may be explained by differing prevalence of the A-61C SNP in the populations studied, which we found to be highly associated with the Hp2 allele. We report the -61C allele to be associated with decreased Hp protein levels (independent of Hp phenotype, confirming in vitro studies. Decreased Hp expression may lead to increased oxidant stress and increased red cell turnover, and facilitate the development of acquired immunity, similar to

  7. The Drosophila melanogaster CHD1 chromatin remodeling factor modulates global chromosome structure and counteracts HP1a and H3K9me2.

    Science.gov (United States)

    Bugga, Lakshmi; McDaniel, Ivy E; Engie, Liana; Armstrong, Jennifer A

    2013-01-01

    CHD1 is a conserved chromatin remodeling factor that localizes to active genes and functions in nucleosome assembly and positioning as well as histone turnover. Mouse CHD1 is required for the maintenance of stem cell pluripotency while human CHD1 may function as a tumor suppressor. To investigate the action of CHD1 on higher order chromatin structure in differentiated cells, we examined the consequences of loss of CHD1 and over-expression of CHD1 on polytene chromosomes from salivary glands of third instar Drosophila melanogaster larvae. We observed that chromosome structure is sensitive to the amount of this remodeler. Loss of CHD1 resulted in alterations of chromosome structure and an increase in the heterochromatin protein HP1a, while over-expression of CHD1 disrupted higher order chromatin structure and caused a decrease in levels of HP1a. Over-expression of an ATPase inactive form of CHD1 did not result in severe chromosomal defects, suggesting that the ATPase activity is required for this in vivo phenotype. Interestingly, changes in CHD1 protein levels did not correlate with changes in the levels of the euchromatin mark H3K4me3 or elongating RNA Polymerase II. Thus, while CHD1 is localized to transcriptionally active regions of the genome, it can function to alter the levels of HP1a, perhaps through changes in methylation of H3K9.

  8. The Drosophila melanogaster CHD1 chromatin remodeling factor modulates global chromosome structure and counteracts HP1a and H3K9me2.

    Directory of Open Access Journals (Sweden)

    Lakshmi Bugga

    Full Text Available CHD1 is a conserved chromatin remodeling factor that localizes to active genes and functions in nucleosome assembly and positioning as well as histone turnover. Mouse CHD1 is required for the maintenance of stem cell pluripotency while human CHD1 may function as a tumor suppressor. To investigate the action of CHD1 on higher order chromatin structure in differentiated cells, we examined the consequences of loss of CHD1 and over-expression of CHD1 on polytene chromosomes from salivary glands of third instar Drosophila melanogaster larvae. We observed that chromosome structure is sensitive to the amount of this remodeler. Loss of CHD1 resulted in alterations of chromosome structure and an increase in the heterochromatin protein HP1a, while over-expression of CHD1 disrupted higher order chromatin structure and caused a decrease in levels of HP1a. Over-expression of an ATPase inactive form of CHD1 did not result in severe chromosomal defects, suggesting that the ATPase activity is required for this in vivo phenotype. Interestingly, changes in CHD1 protein levels did not correlate with changes in the levels of the euchromatin mark H3K4me3 or elongating RNA Polymerase II. Thus, while CHD1 is localized to transcriptionally active regions of the genome, it can function to alter the levels of HP1a, perhaps through changes in methylation of H3K9.

  9. Recruitment of the cohesin loading factor NIPBL to DNA double-strand breaks depends on MDC1, RNF168 and HP1γ in human cells

    International Nuclear Information System (INIS)

    Oka, Yasuyoshi; Suzuki, Keiji; Yamauchi, Motohiro; Mitsutake, Norisato; Yamashita, Shunichi

    2011-01-01

    Highlights: → NIPBL is recruited to DSBs. → Localization of NIPBL to DSBs is regulated by MDC1 and RNF168. → HP1γ is required for NIPBL accumulation at DSBs. -- Abstract: The cohesin loading factor NIPBL is required for cohesin to associate with chromosomes and plays a role in DNA double-strand break (DSB) repair. Although the NIPBL homolog Scc2 is recruited to an enzymatically generated DSB and promotes cohesin-dependent DSB repair in yeast, the mechanism of the recruitment remains poorly understood. Here we show that the human NIPBL is recruited to the sites of DNA damage generated by micro-irradiation as well as to the sites of DSBs induced by homing endonuclease, I-PpoI. The recruitment of NIPBL was impaired by RNAi-mediated knockdown of MDC1 or RNF168, both of which also accumulate at DSBs. We also show that the recruitment of NIPBL to the sites of DNA damage is mediated by its C-terminal region containing HEAT repeats and Heterochromatin protein 1 (HP1) interacting motif. Furthermore, NIPBL accumulation at damaged sites was also compromised by HP1γ depletion. Taken together, our study reveals that human NIPBL is a novel protein recruited to DSB sites, and the recruitment is controlled by MDC1, RNF168 and HP1γ.

  10. Positive Selection Drives the Evolution of rhino, a Member of the Heterochromatin Protein 1 Family in Drosophila.

    Directory of Open Access Journals (Sweden)

    2005-07-01

    Full Text Available Heterochromatin comprises a significant component of many eukaryotic genomes. In comparison to euchromatin, heterochromatin is gene poor, transposon rich, and late replicating. It serves many important biological roles, from gene silencing to accurate chromosome segregation, yet little is known about the evolutionary constraints that shape heterochromatin. A complementary approach to the traditional one of directly studying heterochromatic DNA sequence is to study the evolution of proteins that bind and define heterochromatin. One of the best markers for heterochromatin is the heterochromatin protein 1 (HP1, which is an essential, nonhistone chromosomal protein. Here we investigate the molecular evolution of five HP1 paralogs present in Drosophila melanogaster. Three of these paralogs have ubiquitous expression patterns in adult Drosophila tissues, whereas HP1D/rhino and HP1E are expressed predominantly in ovaries and testes respectively. The HP1 paralogs also have distinct localization preferences in Drosophila cells. Thus, Rhino localizes to the heterochromatic compartment in Drosophila tissue culture cells, but in a pattern distinct from HP1A and lysine-9 dimethylated H3. Using molecular evolution and population genetic analyses, we find that rhino has been subject to positive selection in all three domains of the protein: the N-terminal chromo domain, the C-terminal chromo-shadow domain, and the hinge region that connects these two modules. Maximum likelihood analysis of rhino sequences from 20 species of Drosophila reveals that a small number of residues of the chromo and shadow domains have been subject to repeated positive selection. The rapid and positive selection of rhino is highly unusual for a gene encoding a chromosomal protein and suggests that rhino is involved in a genetic conflict that affects the germline, belying the notion that heterochromatin is simply a passive recipient of "junk DNA" in eukaryotic genomes.

  11. Positive selection drives the evolution of rhino, a member of the heterochromatin protein 1 family in Drosophila.

    Directory of Open Access Journals (Sweden)

    Danielle Vermaak

    2005-07-01

    Full Text Available Heterochromatin comprises a significant component of many eukaryotic genomes. In comparison to euchromatin, heterochromatin is gene poor, transposon rich, and late replicating. It serves many important biological roles, from gene silencing to accurate chromosome segregation, yet little is known about the evolutionary constraints that shape heterochromatin. A complementary approach to the traditional one of directly studying heterochromatic DNA sequence is to study the evolution of proteins that bind and define heterochromatin. One of the best markers for heterochromatin is the heterochromatin protein 1 (HP1, which is an essential, nonhistone chromosomal protein. Here we investigate the molecular evolution of five HP1 paralogs present in Drosophila melanogaster. Three of these paralogs have ubiquitous expression patterns in adult Drosophila tissues, whereas HP1D/rhino and HP1E are expressed predominantly in ovaries and testes respectively. The HP1 paralogs also have distinct localization preferences in Drosophila cells. Thus, Rhino localizes to the heterochromatic compartment in Drosophila tissue culture cells, but in a pattern distinct from HP1A and lysine-9 dimethylated H3. Using molecular evolution and population genetic analyses, we find that rhino has been subject to positive selection in all three domains of the protein: the N-terminal chromo domain, the C-terminal chromo-shadow domain, and the hinge region that connects these two modules. Maximum likelihood analysis of rhino sequences from 20 species of Drosophila reveals that a small number of residues of the chromo and shadow domains have been subject to repeated positive selection. The rapid and positive selection of rhino is highly unusual for a gene encoding a chromosomal protein and suggests that rhino is involved in a genetic conflict that affects the germline, belying the notion that heterochromatin is simply a passive recipient of "junk DNA" in eukaryotic genomes.

  12. Trypanosoma brucei gambiense group 1 is distinguished by a unique amino acid substitution in the HpHb receptor implicated in human serum resistance.

    Directory of Open Access Journals (Sweden)

    Rebecca E Symula

    Full Text Available Trypanosoma brucei rhodesiense (Tbr and T. b. gambiense (Tbg, causative agents of Human African Trypanosomiasis (sleeping sickness in Africa, have evolved alternative mechanisms of resisting the activity of trypanosome lytic factors (TLFs, components of innate immunity in human serum that protect against infection by other African trypanosomes. In Tbr, lytic activity is suppressed by the Tbr-specific serum-resistance associated (SRA protein. The mechanism in Tbg is less well understood but has been hypothesized to involve altered activity and expression of haptoglobin haemoglobin receptor (HpHbR. HpHbR has been shown to facilitate internalization of TLF-1 in T.b. brucei (Tbb, a member of the T. brucei species complex that is susceptible to human serum. By evaluating the genetic variability of HpHbR in a comprehensive geographical and taxonomic context, we show that a single substitution that replaces leucine with serine at position 210 is conserved in the most widespread form of Tbg (Tbg group 1 and not found in related taxa, which are either human serum susceptible (Tbb or known to resist lysis via an alternative mechanism (Tbr and Tbg group 2. We hypothesize that this single substitution contributes to reduced uptake of TLF and thus may play a key role in conferring serum resistance to Tbg group 1. In contrast, similarity in HpHbR sequence among isolates of Tbg group 2 and Tbb/Tbr provides further evidence that human serum resistance in Tbg group 2 is likely independent of HpHbR function.

  13. HP1330 Contributes to Streptococcus suis Virulence by Inducing Toll-Like Receptor 2- and ERK1/2-Dependent Pro-inflammatory Responses and Influencing In Vivo S. suis Loads

    Directory of Open Access Journals (Sweden)

    Qiang Zhang

    2017-07-01

    Full Text Available Streptococcus suis 2 (SS2 has evolved into a highly invasive pathogen responsible for two large-scale outbreaks of streptococcal toxic shock-like syndrome (STSLS in China. Excessive inflammation stimulated by SS2 is considered a hallmark of STSLS, even it also plays important roles in other clinical symptoms of SS2-related disease, including meningitis, septicemia, and sudden death. However, the mechanism of SS2-caused excessive inflammation remains poorly understood. Here, a novel pro-inflammatory protein was identified (HP1330, which could induce robust expression of pro-inflammatory cytokines (TNF-α, MCP-1, and IL-1β in RAW264.7 macrophages. To evaluate the role of HP1330 in SS2 virulence, an hp1330-deletion mutant (Δhp1330 was constructed. In vitro, hp1330 disruption led to a decreased pro-inflammatory ability of SS2 in RAW 264.7 macrophages. In vivo, Δhp1330 showed reduced lethality, pro-inflammatory activity, and bacterial loads in mice. To further elucidate the mechanism of HP1330-induced pro-inflammatory cytokine production, antibody blocking and gene-deletion experiments with macrophages were performed. The results revealed that the pro-inflammatory activity of HP1330 depended on the recognition of toll-like receptor 2 (TLR2. Furthermore, a specific inhibitor of the extracellular signal-regulated kinase 1/2 (ERK1/2 pathways could significantly decrease HP1330-induced pro-inflammatory cytokine production, and western blot analysis showed that HP1330 could induce activation of the ERK1/2 pathway. Taken together, our findings demonstrate that HP1330 contributes to SS2 virulence by inducing TLR2- and ERK1/2-dependent pro-inflammatory cytokine production and influencing in vivo bacterial loads, implying that HP1330 may be associated with STSLS caused by SS2.

  14. Ethnicity/culture modulates the relationships of the haptoglobin (Hp) 1-1 phenotype with cognitive function in older individuals with type 2 diabetes.

    Science.gov (United States)

    Guerrero-Berroa, Elizabeth; Ravona-Springer, Ramit; Heymann, Anthony; Schmeidler, James; Hoffman, Hadas; Preiss, Rachel; Koifmann, Keren; Greenbaum, Lior; Levy, Andrew; Silverman, Jeremy M; Leroith, Derek; Sano, Mary; Schnaider-Beeri, Michal

    2016-05-01

    The haptoglobin (Hp) genotype has been associated with cognitive function in type 2 diabetes. Because ethnicity/culture has been associated with both cognitive function and Hp genotype frequencies, we examined whether it modulates the association of Hp with cognitive function. This cross-sectional study evaluated 787 cognitively normal older individuals (>65 years of age) with type 2 diabetes participating in the Israel Diabetes and Cognitive Decline study. Interactions in two-way analyses of covariance compared Group (Non-Ashkenazi versus Ashkenazi Jews) on the associations of Hp phenotype (Hp 1-1 versus non- Hp 1-1) with five cognitive outcome measures. The primary control variables were age, gender, and education. Compared with Ashkenazi Jews, non-Ashkenazi Jews with the Hp 1-1 phenotype had significantly poorer cognitive function than non-Hp 1-1 in the domains of Attention/Working Memory (p = 0.035) and Executive Function (p = 0.023), but not in Language/Semantic Categorization (p = 0.432), Episodic Memory (p = 0.268), or Overall Cognition (p = 0.082). After controlling for additional covariates (type 2 diabetes-related characteristics, cardiovascular risk factors, Mini-mental State Examination, and extent of depressive symptoms), Attention/Working Memory (p = 0.038) and Executive Function (p = 0.013) remained significant. Older individuals from specific ethnic/cultural backgrounds with the Hp 1-1 phenotype may benefit more from treatment targeted at decreasing or halting the detrimental effects of Hp 1-1 on the brain. Future studies should examine differential associations of Hp 1-1 and cognitive impairment, especially for groups with high prevalence of both, such as African-Americans and Hispanics. Copyright © 2015 John Wiley & Sons, Ltd.

  15. Operation of the HP2250 with the HP9000 series 200 using PASCAL 3.0

    Science.gov (United States)

    Perry, John; Stroud, C. W.

    1986-01-01

    A computer program has been written to provide an interface between the HP Series 200 desktop computers, operating under HP Standard Pascal 3.0, and the HP2250 Data Acquisition and Control System. Pascal 3.0 for the HP9000 desktop computer gives a number of procedures for handling bus communication at various levels. It is necessary, however, to reach the lowest possible level in Pascal to handle the bus protocols required by the HP2250. This makes programming extremely complex since these protocols are not documented. The program described solves those problems and allows the user to immediately program, simply and efficiently, any measurement and control language (MCL/50) application with a few procedure calls. The complete set of procedures is available on a 5 1/4 inch diskette from Cosmic. Included in this group of procedures is an Exerciser which allows the user to exercise his HP2250 interactively. The exerciser operates in a fashion similar to the Series 200 operating system programs, but is adapted to the requirements of the HP2250. The programs on the diskette and the user's manual assume the user is acquainted with both the MCL/50 programming language and HP Standard Pascal 3.0 for the HP series 200 desktop computers.

  16. MeCP2 interacts with HP1 and modulates its heterochromatin association during myogenic differentiation

    Science.gov (United States)

    Agarwal, Noopur; Hardt, Tanja; Brero, Alessandro; Nowak, Danny; Rothbauer, Ulrich; Becker, Annette; Leonhardt, Heinrich; Cardoso, M. Cristina

    2007-01-01

    There is increasing evidence of crosstalk between epigenetic modifications such as histone and DNA methylation, recognized by HP1 and methyl CpG-binding proteins, respectively. We have previously shown that the level of methyl CpG-binding proteins increased dramatically during myogenesis leading to large-scale heterochromatin reorganization. In this work, we show that the level of HP1 isoforms did not change significantly throughout myogenic differentiation but their localization did. In particular, HP1γ relocalization to heterochromatin correlated with MeCP2 presence. Using co-immunoprecipitation assays, we found that these heterochromatic factors interact in vivo via the chromo shadow domain of HP1 and the first 55 amino acids of MeCP2. We propose that this dynamic interaction of HP1 and MeCP2 increases their concentration at heterochromatin linking two major gene silencing pathways to stabilize transcriptional repression during differentiation. PMID:17698499

  17. Arabidopsis SUMO protease ASP1 positively regulates flowering time partially through regulating FLC stability 

    KAUST Repository

    Kong, Xiangxiong; Luo, Xi; Qu, Gao Ping; Liu, Peng; Jin, Jing Bo

    2016-01-01

    The initiation of flowering is tightly regulated by the endogenous and environment signals, which is crucial for the reproductive success of flowering plants. It is well known that autonomous and vernalization pathways repress transcription of FLOWERING LOCUS C (FLC), a focal floral repressor, but how its protein stability is regulated remains largely unknown. Here, we found that mutations in a novel Arabidopsis SUMO protease 1 (ASP1) resulted in a strong late-flowering phenotype under long-days, but to a lesser extent under short-days. ASP1 localizes in the nucleus and exhibited a SUMO protease activity in vitro and in vivo. The conserved Cys-577 in ASP1 is critical for its enzymatic activity, as well as its physiological function in the regulation of flowering time. Genetic and gene expression analyses demonstrated that ASP1 promotes transcription of positive regulators of flowering, such as FT, SOC1 and FD, and may function in both CO-dependent photoperiod pathway and FLC-dependent pathways. Although the transcription level of FLC was not affected in the loss-of-function asp1 mutant, the protein stability of FLC was increased in the asp1 mutant. Taken together, this study identified a novel bona fide SUMO protease, ASP1, which positively regulates transition to flowering at least partly by repressing FLC protein stability.

  18. Arabidopsis SUMO protease ASP1 positively regulates flowering time partially through regulating FLC stability 

    KAUST Repository

    Kong, Xiangxiong

    2016-12-07

    The initiation of flowering is tightly regulated by the endogenous and environment signals, which is crucial for the reproductive success of flowering plants. It is well known that autonomous and vernalization pathways repress transcription of FLOWERING LOCUS C (FLC), a focal floral repressor, but how its protein stability is regulated remains largely unknown. Here, we found that mutations in a novel Arabidopsis SUMO protease 1 (ASP1) resulted in a strong late-flowering phenotype under long-days, but to a lesser extent under short-days. ASP1 localizes in the nucleus and exhibited a SUMO protease activity in vitro and in vivo. The conserved Cys-577 in ASP1 is critical for its enzymatic activity, as well as its physiological function in the regulation of flowering time. Genetic and gene expression analyses demonstrated that ASP1 promotes transcription of positive regulators of flowering, such as FT, SOC1 and FD, and may function in both CO-dependent photoperiod pathway and FLC-dependent pathways. Although the transcription level of FLC was not affected in the loss-of-function asp1 mutant, the protein stability of FLC was increased in the asp1 mutant. Taken together, this study identified a novel bona fide SUMO protease, ASP1, which positively regulates transition to flowering at least partly by repressing FLC protein stability.

  19. Helicobacter pylori antigen HP0986 (TieA) interacts with cultured gastric epithelial cells and induces IL8 secretion via NF-κB mediated pathway.

    Science.gov (United States)

    Devi, Savita; Ansari, Suhail A; Vadivelu, Jamuna; Mégraud, Francis; Tenguria, Shivendra; Ahmed, Niyaz

    2014-02-01

    The envisaged roles and partly understood functional properties of Helicobacter pylori protein HP0986 are significant in the context of proinflammatory and or proapoptotic activities, the two important facilitators of pathogen survival and persistence. In addition, sequence analysis of this gene predicts a restriction endonuclease function which remained unknown thus far. To evaluate the role of HP0986 in gastric inflammation, we studied its expression profile using a large number of clinical isolates but a limited number of biopsies and patient sera. Also, we studied antigenic role of HP0986 in altering cytokine responses of human gastric epithelial (AGS) cells including its interaction with and localization within the AGS cells. For in vitro expression study of HP0986, 110 H. pylori clinical isolates were cultured from patients with functional dyspepsia. For expression analysis by qRT PCR of HP0986, 10 gastric biopsy specimens were studied. HP0986 was also used to detect antibodies in patient sera. AGS cells were incubated with recombinant HP0986 to determine cytokine response and NF-κB activation. Transient transfection with HP0986 cloned in pEGFPN1 was used to study its subcellular localization or homing in AGS cells. Out of 110 cultured H. pylori strains, 34 (31%) were positive for HP0986 and this observation was correlated with in vitro expression profiles. HP0986 mRNA was detected in 7 of the 10 biopsy specimens. Further, HP0986 induced IL-8 secretion in gastric epithelial cells in a dose and time-dependent manner via NF-κB pathway. Serum antibodies against HP0986 were positively associated with H. pylori positive patients. Transient transfection of AGS cells revealed both cytoplasmic and nuclear localization of HP0986. HP0986 was moderately prevalent in clinical isolates and its expression profile in cultures and gastric biopsies points to its being naturally expressed. Collective observations including the induction of IL-8 via TNFR1 and NF

  20. Wnt signaling positively regulates endothelial cell fate specification in the Fli1a-positive progenitor population via Lef1.

    Science.gov (United States)

    Hübner, Kathleen; Grassme, Kathrin S; Rao, Jyoti; Wenke, Nina K; Zimmer, Cordula L; Korte, Laura; Mu Ller, Katja; Sumanas, Saulius; Greber, Boris; Herzog, Wiebke

    2017-10-01

    During vertebrate embryogenesis, vascular endothelial cells (ECs) and primitive erythrocytes become specified within close proximity in the posterior lateral plate mesoderm (LPM) from a common progenitor. However, the signaling cascades regulating the specification into either lineage remain largely elusive. Here, we analyze the contribution of β-catenin dependent Wnt signaling to EC and erythrocyte specification during zebrafish embryogenesis. We generated novel β-catenin dependent Wnt signaling reporters which, by using destabilized fluorophores (Venus-Pest, dGFP), specifically allow us to detect Wnt signaling responses in narrow time windows as well as in spatially restricted domains, defined by Cre recombinase expression (Tg(axin2 BAC :Venus-Pest) mu288 ; Tg(14TCF:loxP-STOP-loxP-dGFP) mu202 ). We therefore can detect β-catenin dependent Wnt signaling activity in a subset of the Fli1a-positive progenitor population. Additionally, we show that mesodermal Wnt3a-mediated signaling via the transcription factor Lef1 positively regulates EC specification (defined by kdrl expression) at the expense of primitive erythrocyte specification (defined by gata1 expression) in zebrafish embryos. Using mesoderm derived from human embryonic stem cells, we identified the same principle of Wnt signaling dependent EC specification in conjunction with auto-upregulation of LEF1. Our data indicate a novel role of β-catenin dependent Wnt signaling in regulating EC specification during vasculogenesis. Copyright © 2017. Published by Elsevier Inc.

  1. Modelling, experimentation and simulation of a reversible HP/ORC unit to get a Positive Energy Building

    DEFF Research Database (Denmark)

    Dumont, Olivier; Carmo, Carolina; Quoilin, Sylvain

    2015-01-01

    This paper presents an innovative building comprising a heat pump connected to a solar roof and a geothermal heat exchanger. This unit is able to invert its cycle and operate as an Organic Rankine Cycle (ORC). The solar roof is producing large amount of heat throughout the year. This allows...... and fluid R134a shows promising performance with a net electrical energy produced over one year reaching 4030 kWh. Following that, a prototype has been built and has proven the feasibility of the technology. Finally, a simulation code including the building, the ground heat exchanger, the thermal energy...... storage, the solar roof and the reversible HP/ORC unit is developed and allows to perform a sensivity analysis. Annual results show that this technology leads to a Positive Energy Building....

  2. Rice homeobox transcription factor HOX1a positively regulates gibberellin responses by directly suppressing EL1.

    Science.gov (United States)

    Wen, Bi-Qing; Xing, Mei-Qing; Zhang, Hua; Dai, Cheng; Xue, Hong-Wei

    2011-11-01

    Homeobox transcription factors are involved in various aspects of plant development, including maintenance of the biosynthesis and signaling pathways of different hormones. However, few direct targets of homeobox proteins have been identified. We here show that overexpression of rice homeobox gene HOX1a resulted in enhanced gibberellin (GA) response, indicating a positive effect of HOX1a in GA signaling. HOX1a is induced by GA and encodes a homeobox transcription factor with transcription repression activity. In addition, HOX1a suppresses the transcription of early flowering1 (EL1), a negative regulator of GA signaling, and further electrophoretic mobility shift assay and chromatin immunoprecipitation analysis revealed that HOX1a directly bound to the promoter region of EL1 to suppress its expression and stimulate GA signaling. These results demonstrate that HOX1a functions as a positive regulator of GA signaling by suppressing EL1, providing informative hints on the study of GA signaling. © 2011 Institute of Botany, Chinese Academy of Sciences.

  3. Differentiation-specific association of HP1alpha and HP1beta with chromocentres is correlated with clustering of TIF1beta at these sites

    Czech Academy of Sciences Publication Activity Database

    Bártová, Eva; Pacherník, J.; Kozubík, Alois; Kozubek, Stanislav

    2007-01-01

    Roč. 127, č. 4 (2007), s. 375-388 ISSN 0948-6143 R&D Projects: GA AV ČR(CZ) 1QS500040508; GA AV ČR(CZ) IAA5004306; GA MŠk(CZ) LC535; GA ČR(CZ) GA204/06/0978; GA ČR(CZ) GP524/03/P171 Institutional research plan: CEZ:AV0Z50040702 Keywords : HP1 proteiny * TIF1beta * chromocentry Subject RIV: BO - Biophysics Impact factor: 2.893, year: 2007

  4. Figure 1. Prediction of ScHP1 transmembrane domains I to XIV. (http ...

    Indian Academy of Sciences (India)

    Figure 2. Comparison of the ScHP1 amino acid sequence with H. +. -PPase from other species. The conserved domains GGG,. DVGADLVGKVE, DNVGDNVGD, EYYT and GNTTAA were found in the sequence alignment (shown in red boxes).

  5. Frequency of helicobacter pylori (hp) infection in children with recurrent abdominal pain (rap)

    International Nuclear Information System (INIS)

    Mahmud, S.; Ali, S.

    2015-01-01

    To study the frequency of Helicobacter Pylori (HP) infection among children with recurrent abdominal pain (RAP) Study Design: Cross-sectional comparative study. Place and Duration of Study: Military Hospital (MH), Rawalpindi from December 2011 to February 2012. Patients and Methods: One hundred children of either gender aged 2 to 12 years presenting with RAP were tested for HP at Paediatric OPD MH, Rawalpindi who consented to participate in the study. Those children who tested positive for Helicobacter Pylori Stool Antigen Test (HPSAT) were labeled as those having Hp infection. The stool assay was performed using the HpSAT kit and the socio-demographic and clinical profiles of children were associated. Results: Out of 100 children included in the study HpSAT was positive in 38% children. Frequency of Hp infection was significantly associated with source of drinking water (p = 0.014), socioeconomic status (p = 0.001) and positive family history of yspepsia (p= 0.023). While age and gender have no significant association with HP infection. Conclusion: Hp infection is very common in children presenting with RAP in our Paediatric OPD. Children with family history of dyspepsia, from low socioeconomic class and those drinking filtered water are at greater risk for HP infection. It is recommended that children from other populations in our country should also be tested in their medical health facilities in order to have a wider analysis of this problem in our setup. (author)

  6. Identification of E2F1 as a positive transcriptional regulator for δ-catenin

    International Nuclear Information System (INIS)

    Kim, Kwonseop; Oh, Minsoo; Ki, Hyunkyoung; Wang Tao; Bareiss, Sonja; Fini, M. Elizabeth.; Li Dawei; Lu Qun

    2008-01-01

    δ-Catenin is upregulated in human carcinomas. However, little is known about the potential transcriptional factors that regulate δ-catenin expression in cancer. Using a human δ-catenin reporter system, we have screened several nuclear signaling modulators to test whether they can affect δ-catenin transcription. Among β-catenin/LEF-1, Notch1, and E2F1, E2F1 dramatically increased δ-catenin-luciferase activities while β-catenin/LEF-1 induced only a marginal increase. Rb suppressed the upregulation of δ-catenin-luciferase activities induced by E2F1 but did not interact with δ-catenin. RT-PCR and Western blot analyses in 4 different prostate cancer cell lines revealed that regulation of δ-catenin expression is controlled mainly at the transcriptional level. Interestingly, the effects of E2F1 on δ-catenin expression were observed only in human cancer cells expressing abundant endogenous δ-catenin. These studies identify E2F1 as a positive transcriptional regulator for δ-catenin, but further suggest the presence of strong negative regulator(s) for δ-catenin in prostate cancer cells with minimal endogenous δ-catenin expression

  7. Comparison of four urease-dependent tests of detecting HP infection

    International Nuclear Information System (INIS)

    Han Yuan; Huang Gang; Zhu Cuiying; Ling Liqun

    2001-01-01

    Objective: The aim of this study is to compare the four urease-dependent tests of detecting Hp infection. The authors used following method: 1) rapid urease test (RUT), 2) 14 C urea breath test ( 14 C-UBT), 3) 13 C urea breath test which is measured by with infrared spectrometry ( 13 C-UBT1), 4) 13 C urea breath test with mass spectrometry ( 13 C-UBT). Methods: 54 patients underwent RUT, 14 C-UBT, 13 C-UBT1, 13 C-UBT2 respectively. Results: Sensitivity and specificity, accurate rate, positive predictive value (PPV), negative predictive value (NPV), respectively, were as follows: RUT (82.1%, 80%, 81.5%, 91.4%, 63.2%), 14 C-UBT (97.4%, 100%, 98.1%, 100%, 93.8%), 13 C-UBT1 (100%, 93.3%, 98.1%, 97.5%, 100%), 13 C-UBT2 (100%, 86.7%, 96.3%, 95.1%, 100%), PPV of four tests are not significantly different (P>0.05). Conclusion: Four urease-dependent tests are high sensitive and accurate methods for detecting Hp infection. UBT is an ideal tool for diagnosis, screen and follow-up of Hp infection

  8. The histone deacetylase HDAC1 positively regulates Notch signaling during Drosophila wing development

    Directory of Open Access Journals (Sweden)

    Zehua Wang

    2018-02-01

    Full Text Available The Notch signaling pathway is highly conserved across different animal species and plays crucial roles in development and physiology. Regulation of Notch signaling occurs at multiple levels in different tissues and cell types. Here, we show that the histone deacetylase HDAC1 acts as a positive regulator of Notch signaling during Drosophila wing development. Depletion of HDAC1 causes wing notches on the margin of adult wing. Consistently, the expression of Notch target genes is reduced in the absence of HDAC1 during wing margin formation. We further provide evidence that HDAC1 acts upstream of Notch activation. Mechanistically, we show that HDAC1 regulates Notch protein levels by promoting Notch transcription. Consistent with this, the HDAC1-associated transcriptional co-repressor Atrophin (Atro is also required for transcriptional activation of Notch in the wing disc. In summary, our results demonstrate that HDAC1 positively regulates Notch signaling and reveal a previously unidentified function of HDAC1 in Notch signaling.

  9. Virus-cell fusion inhibitory activity of novel analogue peptides based on the HP (2-20) derived from N-terminus of Helicobacter pylori Ribosomal Protein L1.

    Science.gov (United States)

    Woo, Eun-Rhan; Lee, Dong Gun; Chang, Young-Su; Park, Yoonkyung; Hahm, Kyung-Soo

    2002-12-01

    HP (2-20) (AKKVFKRLEKLFSKIQNDK) is the antibacterial sequence derived from N-terminus of Helicobacter pylori Ribosomal Protein L1 (RPL1). It has a broad-spectrum microbicidal activity in vitro that is thought to be related to the membrane-disruptive properties of the peptide. Based on the putative membrane-targeted mode of action, we postulated that HP (2-20) might be possessed virus-cell fusion inhibitory activity. To develop the novel virus-cell fusion inhibitory peptides, several analogues with amino acid substitution were designed to increase or decrease only net hydrophobic region. In particular, substitution of Gln and Asp for hydrophobic amino acid, Trp at position 17 and 19 of HP (2-20) (Anal 3) caused a dramatic increase in virus-cell fusion inhibitory activity without hemolytic effect.

  10. A positive feedback regulation of ISL-1 in DLBCL but not in pancreatic β-cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qiao, E-mail: zhangqiao200824@126.com [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China); Yang, Zhe, E-mail: zheyang@bjmu.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China); Wang, Weiping, E-mail: wwp@bjmu.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China); Guo, Ting, E-mail: luckyguoting@bjmu.edu.cn [Department of Gastrointestinal Translation Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital, 52 Fucheng Road, 100142 Beijing (China); Jia, Zhuqing, E-mail: zhuqingjia@126.com [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China); Ma, Kangtao, E-mail: makangtao11@126.com [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China); Zhou, Chunyan, E-mail: chunyanzhou@bjmu.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences (Ministry of Education), Peking University, 38 Xueyuan Road, 100191 Beijing (China)

    2014-07-04

    Highlights: • ISL-1 is highly expressed in human pancreatic β-cells and DLBCL. • ISL-1 accelerates the tumorigenesis of DLBCL in vivo. • c-Myc positively regulates ISL-1 expression in DLBCL but not in pancreatic β-cells. • ISL-1 and c-Myc forms an ISL-1/c-Myc transcriptional complex only in DLBCL. • Positive feedback regulation of ISL-1 does not exist in normal pancreatic β-cell. - Abstract: Insulin enhancer binding protein-1 (ISL-1), a LIM-homeodomain transcription factor, has been reported to play essential roles in promoting adult pancreatic β-cells proliferation. Recent studies indicate that ISL-1 may also involve in the occurrence of a variety of tumors. However, whether ISL-1 has any functional effect on tumorigenesis, and what are the differences on ISL-1 function in distinct conditions, are completely unknown. In this study, we found that ISL-1 was highly expressed in human pancreatic β-cells, as well as in diffuse large B cell lymphoma (DLBCL), but to a much less extent in other normal tissues or tumor specimens. Further study revealed that ISL-1 promoted the proliferation of pancreatic β-cells and DLBCL cells, and also accelerated the tumorigenesis of DLBCL in vivo. We also found that ISL-1 could activate c-Myc transcription not only in pancreatic β-cells but also in DLBCL cells. However, a cell-specific feedback regulation was detectable only in DLBCL cells. This auto-regulatory loop was established by the interaction of ISL-1 and c-Myc to form an ISL-1/c-Myc transcriptional complex, and synergistically to promote ISL-1 transcription through binding on the ISL-1 promoter. Taken together, our results demonstrate a positive feedback regulation of ISL-1 in DLBCL but not in pancreatic β-cells, which might result in the functional diversities of ISL-1 in different physiological and pathological processes.

  11. A positive feedback regulation of ISL-1 in DLBCL but not in pancreatic β-cells

    International Nuclear Information System (INIS)

    Zhang, Qiao; Yang, Zhe; Wang, Weiping; Guo, Ting; Jia, Zhuqing; Ma, Kangtao; Zhou, Chunyan

    2014-01-01

    Highlights: • ISL-1 is highly expressed in human pancreatic β-cells and DLBCL. • ISL-1 accelerates the tumorigenesis of DLBCL in vivo. • c-Myc positively regulates ISL-1 expression in DLBCL but not in pancreatic β-cells. • ISL-1 and c-Myc forms an ISL-1/c-Myc transcriptional complex only in DLBCL. • Positive feedback regulation of ISL-1 does not exist in normal pancreatic β-cell. - Abstract: Insulin enhancer binding protein-1 (ISL-1), a LIM-homeodomain transcription factor, has been reported to play essential roles in promoting adult pancreatic β-cells proliferation. Recent studies indicate that ISL-1 may also involve in the occurrence of a variety of tumors. However, whether ISL-1 has any functional effect on tumorigenesis, and what are the differences on ISL-1 function in distinct conditions, are completely unknown. In this study, we found that ISL-1 was highly expressed in human pancreatic β-cells, as well as in diffuse large B cell lymphoma (DLBCL), but to a much less extent in other normal tissues or tumor specimens. Further study revealed that ISL-1 promoted the proliferation of pancreatic β-cells and DLBCL cells, and also accelerated the tumorigenesis of DLBCL in vivo. We also found that ISL-1 could activate c-Myc transcription not only in pancreatic β-cells but also in DLBCL cells. However, a cell-specific feedback regulation was detectable only in DLBCL cells. This auto-regulatory loop was established by the interaction of ISL-1 and c-Myc to form an ISL-1/c-Myc transcriptional complex, and synergistically to promote ISL-1 transcription through binding on the ISL-1 promoter. Taken together, our results demonstrate a positive feedback regulation of ISL-1 in DLBCL but not in pancreatic β-cells, which might result in the functional diversities of ISL-1 in different physiological and pathological processes

  12. Growth promotion in pigs by oxytetracycline coincides with down regulation of serum inflammatory parameters and of hibernation-associated protein HP-27.

    Science.gov (United States)

    Soler, Laura; Miller, Ingrid; Hummel, Karin; Razzazi-Fazeli, Ebrahim; Jessen, Flemming; Escribano, Damian; Niewold, Theo

    2016-05-01

    The growth promoting effect of supplementing animal feed with antibiotics like tetracycline has traditionally been attributed to their antibiotic character. However, more evidence has been accumulated on their direct anti-inflammatory effect during the last two decades. Here we used a pig model to explore the systemic molecular effect of feed supplementation with sub therapeutic levels of oxytetracycline (OTC) by analysis of serum proteome changes. Results showed that OTC promoted growth, coinciding with a significant down regulation of different serum proteins related to inflammation, oxidation and lipid metabolism, confirming the anti-inflammatory mechanism of OTC. Interestingly, apart from the classic acute phase reactants also down regulation was seen of a hibernation associated plasma protein (HP-27), which is to our knowledge the first description in pigs. Although the exact function in non-hibernators is unclear, down regulation of HP-27 could be consistent with increased appetite, which is possibly linked to the anti-inflammatory action of OTC. Given that pigs are good models for human medicine due to their genetic and physiologic resemblance, the present results might also be used for rational intervention in human diseases in which inflammation plays an important role such as obesity, type 2 diabetes and cardiovascular diseases. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Clinical value of 13C-UBT diagnosing infection of the Hp

    International Nuclear Information System (INIS)

    Xu Changde; Chen Shaoliang; Liu Wenguan

    2004-01-01

    100 dyspeptic patients are performed an endoscopy with biopsy for histology, rapid urease test, 13 C-urea breath test( 13 C-UBT) and ASSURE TM Hp rapid Test(HpRT). Patients are considered to be infected if both histology and biopsies yield positive results, and not infected when both tests are negative. The pathology and persons responsible for endoscopy, urease test and 13 C-UBT are unaware of the results from the other diagnostic methods. The 13 C-UBT has the following results: sensitivity 96% ,specificity 95%; rapid urease test has the following results: sensitivity 79%, specificity 76%; HpRT has the following results: sensitivity 86%, specificity 88%. 13 C-UBT provides excellent sensitivity and specificity for the diagnosis of Hp. Pylori infected Hp, it can be the first choice for detecting the infection of the Hp. (authors)

  14. Body indices and basic vital signs in Helicobacter pylori positive and negative persons

    International Nuclear Information System (INIS)

    Kopacova, Marcela; Bures, Jan; Koupil, Ilona; Rejchrt, Stanislav; Vorisek, Viktor; Seifert, Bohumil; Pozler, Oldrich; Zivny, Pavel; Douda, Tomas; Palicka, Vladimir; Holcik, Jan

    2007-01-01

    It has been hypothesized that Helicobacter pylori (Hp) infection may contribute to reduced stature, risk of hypertension or obesity. The aim was to evaluate body indices in Hp positive and negative persons. A total of 2436 subjects (4-100 years old) were tested for Hp status by 13 C-urea breath test. Data on height and weight were collected for 84%, and blood pressure for 80% of the study subjects. The prevalence of Hp infection was 41.6%. The odds ratio for a 10-year increase in age was 1.21 (95% CI 1.17-1.25, p-value <0.001). Statistically significant negative association of Hp positivity with body height was most pronounced in the younger age groups, while a positive association of Hp positivity with body mass index was only seen in those aged 15+ years. There was a negative effect of Hp positivity on systolic and diastolic blood pressure in subjects below 25 and a relatively strong positive effect on blood pressure in subjects over 65 years. Residual confounding by social characteristics as a possible explanation for the associations of Hp positivity with height and blood pressure cannot be excluded. Unmeasured factors related to social and family environment may cause the apparent association between Hp positivity and children's growth and blood pressure

  15. Epigenetic aspects of HP1 exchange kinetics in apoptotic chromatin

    Czech Academy of Sciences Publication Activity Database

    Legartová, Soňa; Jugová, Alžbeta; Stixová, Lenka; Kozubek, Stanislav; Fojtová, Miloslava; Zdráhal, Z.; Lochmanová, G.; Bártová, Eva

    2013-01-01

    Roč. 95, č. 2 (2013), s. 167-179 ISSN 0300-9084 R&D Projects: GA ČR(CZ) GAP302/10/1022; GA ČR(CZ) GBP302/12/G157; GA MŠk(CZ) LD11020; GA MŠk(CZ) ED1.1.00/02.0068 Institutional research plan: CEZ:AV0Z50040702 Institutional support: RVO:68081707 Keywords : Apoptosis * Histones * HP1 Subject RIV: BO - Biophysics Impact factor: 3.123, year: 2013

  16. HP 9816

    CERN Multimedia

    1982-01-01

    The 9816 was introduced in late 1982. This was the low-cost model in the 200 Series range. It only had two expansion slots and featured a monitor integrated with the system unit and modular keyboard and mass storage (usually a 9121 dual 3.5 inch floppy drive). The monitor was nine inches diagonally with a 400 by 300 dot resolution. The HP 9816 was also designated as the HP 9000 216. It did not include any disk drives but it had a built-in 9 inch monochrome monitor, built-in HP-IB and RS-232 ports and 2 expansion slots. The standard keyboard for the 9816 is a itty-bitty number. The 9816 A came with 128K bytes of memory. The 9816 S included all of the above plus disk based BASIC and a card containing an additional 256K of memory bringing the total memory to 512K but only leaving only one expansion slot open.

  17. Haptoglobin genotyping of Vietnamese: global distribution of HP del, complete deletion allele of the HP gene.

    Science.gov (United States)

    Soejima, Mikiko; Agusa, Tetsuro; Iwata, Hisato; Fujihara, Junko; Kunito, Takashi; Takeshita, Haruo; Lan, Vi Thi Mai; Minh, Tu Binh; Takahashi, Shin; Trang, Pham Thi Kim; Viet, Pham Hung; Tanabe, Shinsuke; Koda, Yoshiro

    2015-01-01

    The haptoglobin (HP) gene deletion allele (HP(del)) is responsible for anhaptoglobinemia and a genetic risk factor for anaphylaxis reaction after transfusion due to production of the anti-HP antibody. The distribution of this allele has been explored by several groups including ours. Here, we studied the frequency of HP(del) in addition to the distribution of common HP genotypes in 293 Vietnamese. The HP(del) was encountered with the frequency of 0.020. The present result suggested that this deletion allele is restricted to East and Southeast Asians. Thus, this allele seems to be a potential ancestry informative marker for these populations. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Heterochromatin marks HP1γ, HP1α and H3K9me3, and DNA damage response activation in human testis development and germ cell tumours

    DEFF Research Database (Denmark)

    Bartkova, J; Moudry, P; Hodny, Z

    2011-01-01

    activation in CIS; and enhanced HP1α in teratoma structures with epithelial and neuronal differentiation. Differential expression of the three heterochromatin markers suggests their partly non-overlapping roles, and separation of heterochromatinization from DDR activation highlights distinct responses...

  19. SIRT1 is a positive regulator of the master osteoblast transcription factor, RUNX2.

    Directory of Open Access Journals (Sweden)

    Kayvan Zainabadi

    Full Text Available Activation of SIRT1 has previously been shown to protect mice against osteoporosis through yet ill-defined mechanisms. In this study, we outline a role for SIRT1 as a positive regulator of the master osteoblast transcription factor, RUNX2. We find that ex vivo deletion of sirt1 leads to decreased expression of runx2 downstream targets, but not runx2 itself, along with reduced osteoblast differentiation. Reciprocally, treatment with a SIRT1 agonist promotes osteoblast differentiation, as well as the expression of runx2 downstream targets, in a SIRT1-dependent manner. Biochemical and luciferase reporter assays demonstrate that SIRT1 interacts with and promotes the transactivation potential of RUNX2. Intriguingly, mice treated with the SIRT1 agonist, resveratrol, show similar increases in the expression of RUNX2 targets in their calvaria (bone tissue, validating SIRT1 as a physiologically relevant regulator of RUNX2.

  20. HP advances Grid Strategy for the adaptive enterprise

    CERN Multimedia

    2003-01-01

    "HP today announced plans to further enable its enterprise infrastructure technologies for grid computing. By leveraging open grid standards, HP plans to help customers simplify the use and management of distributed IT resources. The initiative will integrate industry grid standards, including the Globus Toolkit and Open Grid Services Architecture (OGSA), across HP's enterprise product lines" (1 page).

  1. Functional study of the Hap4-like genes suggests that the key regulators of carbon metabolism HAP4 and oxidative stress response YAP1 in yeast diverged from a common ancestor.

    Directory of Open Access Journals (Sweden)

    Nataliya Petryk

    Full Text Available The transcriptional regulator HAP4, induced by respiratory substrates, is involved in the balance between fermentation and respiration in S. cerevisiae. We identified putative orthologues of the Hap4 protein in all ascomycetes, based only on a conserved sixteen amino acid-long motif. In addition to this motif, some of these proteins contain a DNA-binding motif of the bZIP type, while being nonetheless globally highly divergent. The genome of the yeast Hansenula polymorpha contains two HAP4-like genes encoding the protein HpHap4-A which, like ScHap4, is devoid of a bZIP motif, and HpHap4-B which contains it. This species has been chosen for a detailed examination of their respective properties. Based mostly on global gene expression studies performed in the S. cerevisiae HAP4 disruption mutant (ScΔhap4, we show here that HpHap4-A is functionally equivalent to ScHap4, whereas HpHap4-B is not. Moreover HpHAP4-B is able to complement the H2O2 hypersensitivity of the ScYap1 deletant, YAP1 being, in S. cerevisiae, the main regulator of oxidative stress. Finally, a transcriptomic analysis performed in the ScΔyap1 strain overexpressing HpHAP4-B shows that HpHap4-B acts both on oxidative stress response and carbohydrate metabolism in a manner different from both ScYap1 and ScHap4. Deletion of these two genes in their natural host, H. polymorpha, confirms that HpHAP4-A participates in the control of the fermentation/respiration balance, while HpHAP4-B is involved in oxidative stress since its deletion leads to hypersensitivity to H2O2. These data, placed in an evolutionary context, raise new questions concerning the evolution of the HAP4 transcriptional regulation function and suggest that Yap1 and Hap4 have diverged from a unique regulatory protein in the fungal ancestor.

  2. Erk1 positively regulates osteoclast differentiation and bone resorptive activity.

    Directory of Open Access Journals (Sweden)

    Yongzheng He

    Full Text Available The extracellular signal-regulated kinases (ERK1 and 2 are widely-expressed and they modulate proliferation, survival, differentiation, and protein synthesis in multiple cell lineages. Altered ERK1/2 signaling is found in several genetic diseases with skeletal phenotypes, including Noonan syndrome, Neurofibromatosis type 1, and Cardio-facio-cutaneous syndrome, suggesting that MEK-ERK signals regulate human skeletal development. Here, we examine the consequence of Erk1 and Erk2 disruption in multiple functions of osteoclasts, specialized macrophage/monocyte lineage-derived cells that resorb bone. We demonstrate that Erk1 positively regulates osteoclast development and bone resorptive activity, as genetic disruption of Erk1 reduced osteoclast progenitor cell numbers, compromised pit formation, and diminished M-CSF-mediated adhesion and migration. Moreover, WT mice reconstituted long-term with Erk1(-/- bone marrow mononuclear cells (BMMNCs demonstrated increased bone mineral density as compared to recipients transplanted with WT and Erk2(-/- BMMNCs, implicating marrow autonomous, Erk1-dependent osteoclast function. These data demonstrate Erk1 plays an important role in osteoclast functions while providing rationale for the development of Erk1-specific inhibitors for experimental investigation and/or therapeutic modulation of aberrant osteoclast function.

  3. Differential regulation of renal Klotho and FGFR1 in normal and uremic rats.

    Science.gov (United States)

    Muñoz-Castañeda, Juan R; Herencia, Carmen; Pendón-Ruiz de Mier, Maria Victoria; Rodriguez-Ortiz, Maria Encarnación; Diaz-Tocados, Juan M; Vergara, Noemi; Martínez-Moreno, Julio M; Salmerón, Maria Dolores; Richards, William G; Felsenfeld, Arnold; Kuro-O, Makoto; Almadén, Yolanda; Rodríguez, Mariano

    2017-09-01

    In renal failure, hyperphosphatemia occurs despite a marked elevation in serum fibroblast growth factor (FGF)-23. Abnormal regulation of the FGFR1-Klotho receptor complex may cause a resistance to the phosphaturic action of FGF23. The purpose of the present study was to investigate the regulation of renal Klotho and FGF receptor (FEFR)-1 in healthy and uremic rats induced by 5/6 nephrectomy. In normal rats, the infusion of rat recombinant FGF23 enhanced phosphaturia and increased renal FGFR1 expression; however, Klotho expression was reduced. Uremic rats on a high-phosphate (HP) diet presented hyperphosphatemia with marked elevation of FGF23 and an increased fractional excretion of phosphate (P) that was associated with a marked reduction of Klotho expression and an increase in FGFR1. After neutralization of FGF23 by anti-FGF23 administration, phosphaturia was still abundant, Klotho expression remained low, and the FGFR1 level was reduced. These results suggest that the expression of renal Klotho is modulated by phosphaturia, whereas the FGFR1 expression is regulated by FGF23. Calcitriol (CTR) administration prevented a decrease in renal Klotho expression. In HEK293 cells HP produced nuclear translocation of β-catenin, together with a reduction in Klotho. Wnt/β-catenin inhibition with Dkk-1 prevented the P-induced down-regulation of Klotho. The addition of CTR to HP medium was able to recover Klotho expression. In summary, high FGF23 levels increase FGFR1, whereas phosphaturia decreases Klotho expression through the activation of Wnt/β-catenin pathway.-Muñoz-Castañeda, J. R., Herencia, C., Pendón-Ruiz de Mier, M. V., Rodriguez-Ortiz, M. E., Diaz-Tocados, J. M., Vergara, N., Martínez-Moreno, J. M., Salmerón, M. D., Richards, W. G., Felsenfeld, A., Kuro-O, M., Almadén, Y., Rodríguez, M. Differential regulation of renal Klotho and FGFR1 in normal and uremic rats. © FASEB.

  4. Bluetongue virus non-structural protein 1 is a positive regulator of viral protein synthesis

    Directory of Open Access Journals (Sweden)

    Boyce Mark

    2012-08-01

    Full Text Available Abstract Background Bluetongue virus (BTV is a double-stranded RNA (dsRNA virus of the Reoviridae family, which encodes its genes in ten linear dsRNA segments. BTV mRNAs are synthesised by the viral RNA-dependent RNA polymerase (RdRp as exact plus sense copies of the genome segments. Infection of mammalian cells with BTV rapidly replaces cellular protein synthesis with viral protein synthesis, but the regulation of viral gene expression in the Orbivirus genus has not been investigated. Results Using an mRNA reporter system based on genome segment 10 of BTV fused with GFP we identify the protein characteristic of this genus, non-structural protein 1 (NS1 as sufficient to upregulate translation. The wider applicability of this phenomenon among the viral genes is demonstrated using the untranslated regions (UTRs of BTV genome segments flanking the quantifiable Renilla luciferase ORF in chimeric mRNAs. The UTRs of viral mRNAs are shown to be determinants of the amount of protein synthesised, with the pre-expression of NS1 increasing the quantity in each case. The increased expression induced by pre-expression of NS1 is confirmed in virus infected cells by generating a replicating virus which expresses the reporter fused with genome segment 10, using reverse genetics. Moreover, NS1-mediated upregulation of expression is restricted to mRNAs which lack the cellular 3′ poly(A sequence identifying the 3′ end as a necessary determinant in specifically increasing the translation of viral mRNA in the presence of cellular mRNA. Conclusions NS1 is identified as a positive regulator of viral protein synthesis. We propose a model of translational regulation where NS1 upregulates the synthesis of viral proteins, including itself, and creates a positive feedback loop of NS1 expression, which rapidly increases the expression of all the viral proteins. The efficient translation of viral reporter mRNAs among cellular mRNAs can account for the observed

  5. Bluetongue virus non-structural protein 1 is a positive regulator of viral protein synthesis.

    Science.gov (United States)

    Boyce, Mark; Celma, Cristina C P; Roy, Polly

    2012-08-29

    Bluetongue virus (BTV) is a double-stranded RNA (dsRNA) virus of the Reoviridae family, which encodes its genes in ten linear dsRNA segments. BTV mRNAs are synthesised by the viral RNA-dependent RNA polymerase (RdRp) as exact plus sense copies of the genome segments. Infection of mammalian cells with BTV rapidly replaces cellular protein synthesis with viral protein synthesis, but the regulation of viral gene expression in the Orbivirus genus has not been investigated. Using an mRNA reporter system based on genome segment 10 of BTV fused with GFP we identify the protein characteristic of this genus, non-structural protein 1 (NS1) as sufficient to upregulate translation. The wider applicability of this phenomenon among the viral genes is demonstrated using the untranslated regions (UTRs) of BTV genome segments flanking the quantifiable Renilla luciferase ORF in chimeric mRNAs. The UTRs of viral mRNAs are shown to be determinants of the amount of protein synthesised, with the pre-expression of NS1 increasing the quantity in each case. The increased expression induced by pre-expression of NS1 is confirmed in virus infected cells by generating a replicating virus which expresses the reporter fused with genome segment 10, using reverse genetics. Moreover, NS1-mediated upregulation of expression is restricted to mRNAs which lack the cellular 3' poly(A) sequence identifying the 3' end as a necessary determinant in specifically increasing the translation of viral mRNA in the presence of cellular mRNA. NS1 is identified as a positive regulator of viral protein synthesis. We propose a model of translational regulation where NS1 upregulates the synthesis of viral proteins, including itself, and creates a positive feedback loop of NS1 expression, which rapidly increases the expression of all the viral proteins. The efficient translation of viral reporter mRNAs among cellular mRNAs can account for the observed replacement of cellular protein synthesis with viral protein

  6. YY1 positively regulates human UBIAD1 expression

    International Nuclear Information System (INIS)

    Funahashi, Nobuaki; Hirota, Yoshihisa; Nakagawa, Kimie; Sawada, Natumi; Watanabe, Masato; Suhara, Yoshitomo; Okano, Toshio

    2015-01-01

    Vitamin K is involved in bone formation and blood coagulation. Natural vitamin K compounds are composed of the plant form phylloquinone (vitamin K 1 ) and a series of bacterial menaquionones (MK-n; vitamin K 2 ). Menadione (vitamin K 3 ) is an artificial vitamin K compound. MK-4 contains 4-isoprenyl as a side group in the 2-methyl-1,4-naphthoquinone common structure and has various bioactivities. UbiA prenyltransferase domain containing 1 (UBIAD1 or TERE1) is the menaquinone-4 biosynthetic enzyme. UBIAD1 transcript expression significantly decreases in patients with prostate carcinoma and overexpressing UBIAD1 inhibits proliferation of a tumour cell line. UBIAD1 mRNA expression is ubiquitous in mouse tissues, and higher UBIAD1 mRNA expression levels are detected in the brain, heart, kidneys and pancreas. Several functions of UBIAD1 have been reported; however, regulation of the human UBIAD1 gene has not been elucidated. Here we report cloning and characterisation of the human UBIAD1 promoter. A 5′ rapid amplification of cDNA ends analysis revealed that the main transcriptional start site was 306 nucleotides upstream of the translation initiation codon. Deletion and mutation analyses revealed the functional importance of the YY1 consensus motif. Electrophoretic gel mobility shift and chromatin immunoprecipitation assays demonstrated that YY1 binds the UBIAD1 promoter in vitro and in vivo. In addition, YY1 small interfering RNA decreased endogenous UBIAD1 mRNA expression and UBIAD1 conversion activity. These results suggest that YY1 up-regulates UBIAD1 expression and UBIAD1 conversion activity through the UBIAD1 promoter. - Highlights: • We cloned the human UBIAD1 promoter. • The functional importance of the YY1 motif was identified in the UBIAD1 promoter. • YY1 binds the UBIAD1 promoter in vitro and in vivo. • Knockdown of YY1 significantly decreased UBIAD1 expression. • YY1 up-regulates UBIAD1 conversion activity through the UBIAD1 promoter

  7. YY1 positively regulates human UBIAD1 expression

    Energy Technology Data Exchange (ETDEWEB)

    Funahashi, Nobuaki, E-mail: nfunahashi@ri.ncgm.go.jp [Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe (Japan); Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo (Japan); Hirota, Yoshihisa [Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe (Japan); Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka (Japan); Nakagawa, Kimie; Sawada, Natumi; Watanabe, Masato [Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe (Japan); Suhara, Yoshitomo [Department of Bioscience and Engineering, Shibaura Institute of Technology, Saitama (Japan); Okano, Toshio [Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe (Japan)

    2015-05-01

    Vitamin K is involved in bone formation and blood coagulation. Natural vitamin K compounds are composed of the plant form phylloquinone (vitamin K{sub 1}) and a series of bacterial menaquionones (MK-n; vitamin K{sub 2}). Menadione (vitamin K{sub 3}) is an artificial vitamin K compound. MK-4 contains 4-isoprenyl as a side group in the 2-methyl-1,4-naphthoquinone common structure and has various bioactivities. UbiA prenyltransferase domain containing 1 (UBIAD1 or TERE1) is the menaquinone-4 biosynthetic enzyme. UBIAD1 transcript expression significantly decreases in patients with prostate carcinoma and overexpressing UBIAD1 inhibits proliferation of a tumour cell line. UBIAD1 mRNA expression is ubiquitous in mouse tissues, and higher UBIAD1 mRNA expression levels are detected in the brain, heart, kidneys and pancreas. Several functions of UBIAD1 have been reported; however, regulation of the human UBIAD1 gene has not been elucidated. Here we report cloning and characterisation of the human UBIAD1 promoter. A 5′ rapid amplification of cDNA ends analysis revealed that the main transcriptional start site was 306 nucleotides upstream of the translation initiation codon. Deletion and mutation analyses revealed the functional importance of the YY1 consensus motif. Electrophoretic gel mobility shift and chromatin immunoprecipitation assays demonstrated that YY1 binds the UBIAD1 promoter in vitro and in vivo. In addition, YY1 small interfering RNA decreased endogenous UBIAD1 mRNA expression and UBIAD1 conversion activity. These results suggest that YY1 up-regulates UBIAD1 expression and UBIAD1 conversion activity through the UBIAD1 promoter. - Highlights: • We cloned the human UBIAD1 promoter. • The functional importance of the YY1 motif was identified in the UBIAD1 promoter. • YY1 binds the UBIAD1 promoter in vitro and in vivo. • Knockdown of YY1 significantly decreased UBIAD1 expression. • YY1 up-regulates UBIAD1 conversion activity through the UBIAD1

  8. Stress-induced alterations in 5-HT1A receptor transcriptional modulators NUDR and Freud-1.

    Science.gov (United States)

    Szewczyk, Bernadeta; Kotarska, Katarzyna; Daigle, Mireille; Misztak, Paulina; Sowa-Kucma, Magdalena; Rafalo, Anna; Curzytek, Katarzyna; Kubera, Marta; Basta-Kaim, Agnieszka; Nowak, Gabriel; Albert, Paul R

    2014-11-01

    The effect of stress on the mRNA and protein level of the 5-HT1A receptor and two of its key transcriptional modulators, NUDR and Freud-1, was examined in the prefrontal cortex (PFC) and hippocampus (Hp) using rodent models: olfactory bulbectomy (OB) and prenatal stress (PS) in male and female rats; chronic mild stress in male rats (CMS) and pregnancy stress. In PFC, CMS induced the most widespread changes, with significant reduction in both mRNA and protein levels of NUDR, 5-HT1A receptor and in Freud-1 mRNA; while in Hp 5-HT1A receptor and Freud-1 protein levels were also decreased. In male, but not female OB rats PFC Freud-1 and 5-HT1A receptor protein levels were reduced, while in Hp 5-HT1A receptor, Freud-1 and NUDR mRNA's but not protein were reduced. In PS rats PFC 5-HT1A receptor protein was reduced more in females than males; while in Hp Freud-1 protein was increased in females. In pregnancy stress, PFC NUDR, Freud-1 and 5-HT1A protein receptor levels were reduced, and in HP 5-HT1A receptor protein levels were also reduced; in HP only NUDR and Freud-1 mRNA levels were reduced. Overall, CMS and stress during pregnancy produced the most salient changes in 5-HT1A receptor and transcription factor expression, suggesting a primary role for altered transcription factor expression in chronic regulation of 5-HT1A receptor expression. By contrast, OB (in males) and PS (in females) produced gender-specific reductions in PFC 5-HT1A receptor protein levels, suggesting a role for post-transcriptional regulation. These and previous data suggest that chronic stress might be a key regulator of NUDR/Freud-1 gene expression.

  9. HpARI Protein Secreted by a Helminth Parasite Suppresses Interleukin-33.

    Science.gov (United States)

    Osbourn, Megan; Soares, Dinesh C; Vacca, Francesco; Cohen, E Suzanne; Scott, Ian C; Gregory, William F; Smyth, Danielle J; Toivakka, Matilda; Kemter, Andrea M; le Bihan, Thierry; Wear, Martin; Hoving, Dennis; Filbey, Kara J; Hewitson, James P; Henderson, Holly; Gonzàlez-Cìscar, Andrea; Errington, Claire; Vermeren, Sonja; Astier, Anne L; Wallace, William A; Schwarze, Jürgen; Ivens, Alasdair C; Maizels, Rick M; McSorley, Henry J

    2017-10-17

    Infection by helminth parasites is associated with amelioration of allergic reactivity, but mechanistic insights into this association are lacking. Products secreted by the mouse parasite Heligmosomoides polygyrus suppress type 2 (allergic) immune responses through interference in the interleukin-33 (IL-33) pathway. Here, we identified H. polygyrus Alarmin Release Inhibitor (HpARI), an IL-33-suppressive 26-kDa protein, containing three predicted complement control protein (CCP) modules. In vivo, recombinant HpARI abrogated IL-33, group 2 innate lymphoid cell (ILC2) and eosinophilic responses to Alternaria allergen administration, and diminished eosinophilic responses to Nippostrongylus brasiliensis, increasing parasite burden. HpARI bound directly to both mouse and human IL-33 (in the cytokine's activated state) and also to nuclear DNA via its N-terminal CCP module pair (CCP1/2), tethering active IL-33 within necrotic cells, preventing its release, and forestalling initiation of type 2 allergic responses. Thus, HpARI employs a novel molecular strategy to suppress type 2 immunity in both infection and allergy. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  10. HP-SEE User Forum 2012

    CERN Document Server

    Karaivanova, Aneta; Oulas, Anastasis; Liabotis, Ioannis; Stojiljkovic, Danica; Prnjat, Ognjen

    2014-01-01

    This book is a collection of carefully reviewed papers presented during the HP-SEE User Forum, the meeting of the High-Performance Computing Infrastructure for South East Europe’s (HP-SEE) Research Communities, held in October 17-19, 2012, in Belgrade, Serbia. HP-SEE aims at supporting and integrating regional HPC infrastructures; implementing solutions for HPC in the region; and making HPC resources available to research communities in SEE, region, which are working in a number of scientific fields with specific needs for massively parallel execution on powerful computing resources. HP-SEE brings together research communities and HPC operators from 14 different countries and enables them to share HPC facilities, software, tools, data and research results, thus fostering collaboration and strengthening the regional and national human network; the project specifically supports research groups in the areas of computational physics, computational chemistry and the life sciences. The contributions presented i...

  11. 75 FR 62424 - EDS, an HP Company (Re-Branded as HP-Enterprise Services) Including On-Site Workers From: Abel...

    Science.gov (United States)

    2010-10-08

    ...-Branded as HP--Enterprise Services) Including On-Site Workers From: Abel Personnel Inc., Advantage Tech... February 4, 2010, applicable to workers of EDS, an HP Company (Re- branded as HP--Enterprise Services...-branded as HP-- Enterprise Services). These employees provided various activities related to the supply of...

  12. Dynamic variation of histone H3 trimethyl Lys4 (H3K4me3) and heterochromatin protein 1 (HP1) with employment length in nickel smelting workers.

    Science.gov (United States)

    Zhao, Yanhong; Cheng, Ning; Dai, Min; Pu, Hongquan; Zheng, Tongzhang; Li, Haiyan; He, Jie; Bai, Yana

    2017-07-01

    To investigate the dynamic variation in H3K4me3 and HP1 with employment length in nickel smelting workers. Blood samples were collected from 140 nickel smelting workers and 140 age-matched office workers to test for H3K4me3, and HP1 levels. H3K4me3 was statistically significantly different (p exposure to nickel can induce oxidative damage, and increase H3K4me3 expression and inhibit HP1 expression.

  13. Evaluation of HP0605 and HP0971 genes of efflux pumps in Helicobacter pylori resistance to Metronidazole

    Directory of Open Access Journals (Sweden)

    Mohammad hasan Shirazi

    2009-12-01

    Full Text Available Background: The presence of antibiotic resistance has been reported in H.pylori and it is a major cause of treatment failure. Five families of multidrug efflux pumps are defined in bacteria and resistance-nodulation-division (RND pumps are found mainly in gram negative bacteria. TolC is one of RND pump components and play a critical role in drug resistance. It hasn’t been established that RND family has a role in drug resistance in H.pylori. In this study, we assessed the role of two efflux genes in resistant to metronidazole in H.pylori by evaluation of overexpression TolC genes by RT-PCR method. Methods: In five metronidazole resistant strains of H.pylori, total RNA was extracted. RNA treated with DNase and RNA reverse transcribed to cDNA. Aliquots of the cDNA solution were assayed by RT- PCR for HP0605 and HP0971 genes. The levels of mRNA expression were evaluated by densitometry analysis. Results: All five strains displayed overexpression for HP0605 basis of increased concentration of metronidazole. Three strains showed transcripts for HP0971. One of these had transcripts for HP0971 only in Metronidazole concentration equaled to 16 µg/ml but two strains overexpressed adapt to increase concentration of metronidazole. Conclusion: According to current study, HP0605 and HP0971 genes overexpressed due to increase metronidazole. So, increasing of Metronidazole affects in H.pylori΄s efflux system in transcription level.

  14. The Inflammation-Related Gene S100A12 Is Positively Regulated by C/EBPβ and AP-1 in Pigs

    Directory of Open Access Journals (Sweden)

    Xinyun Li

    2014-08-01

    Full Text Available S100A12 is involved in the inflammatory response and is considered an important marker for many inflammatory diseases in humans. Our previous studies indicated that the S100A12 gene was abundant in the immune tissues of pigs and was significantly upregulated during infection with Haemophilus parasuis (HPS or porcine circovirus type 2 (PCV2. In this study, the mechanism of transcriptional regulation of S100A12 was investigated in pigs. Our results showed that S100A12, CCAAT/enhancer-binding protein beta (C/EBPβ and activator protein-1 (AP-1 genes were up-regulated in PK-15 (ATCC, CCL-33 cells when treated with LPS or Poly I: C. Additionally, the promoter activity and expression level of the S100A12 gene were significantly upregulated when C/EBPβ or AP-1 were overexpressed. We utilized electromobility shift assays (EMSA to confirm that C/EBPβ and AP-1 could directly bind the S100A12 gene promoter. We also found that the transcriptional activity and expression levels of C/EBPβ and AP-1 could positively regulate each other. Furthermore, the promoter activity of the S100A12 gene was higher when C/EBPβ and AP-1 were cotransfected than when they were transfected individually. We concluded that the S100A12 gene was cooperatively and positively regulated by C/EBPβ and AP-1 in pigs. Our study offers new insight into the transcriptional regulation of the S100A12 gene.

  15. A parallel direct solver for the self-adaptive hp Finite Element Method

    KAUST Repository

    Paszyński, Maciej R.

    2010-03-01

    In this paper we present a new parallel multi-frontal direct solver, dedicated for the hp Finite Element Method (hp-FEM). The self-adaptive hp-FEM generates in a fully automatic mode, a sequence of hp-meshes delivering exponential convergence of the error with respect to the number of degrees of freedom (d.o.f.) as well as the CPU time, by performing a sequence of hp refinements starting from an arbitrary initial mesh. The solver constructs an initial elimination tree for an arbitrary initial mesh, and expands the elimination tree each time the mesh is refined. This allows us to keep track of the order of elimination for the solver. The solver also minimizes the memory usage, by de-allocating partial LU factorizations computed during the elimination stage of the solver, and recomputes them for the backward substitution stage, by utilizing only about 10% of the computational time necessary for the original computations. The solver has been tested on 3D Direct Current (DC) borehole resistivity measurement simulations problems. We measure the execution time and memory usage of the solver over a large regular mesh with 1.5 million degrees of freedom as well as on the highly non-regular mesh, generated by the self-adaptive h p-FEM, with finite elements of various sizes and polynomial orders of approximation varying from p = 1 to p = 9. From the presented experiments it follows that the parallel solver scales well up to the maximum number of utilized processors. The limit for the solver scalability is the maximum sequential part of the algorithm: the computations of the partial LU factorizations over the longest path, coming from the root of the elimination tree down to the deepest leaf. © 2009 Elsevier Inc. All rights reserved.

  16. Silent decision: HP1 protein escorts heterochromatic RNAs to their destiny

    Science.gov (United States)

    Ren, Jie; Martienssen, Robert A

    2012-01-01

    EMBO J advance online publication 06072012; doi:10.1016/j.molcel.2012.05.009 Heterochromatin is classically perceived to be refractory to transcription because of its compact structure. However, Keller et al (2012) now demonstrated that heterochromatic transcripts can accumulate even when heterochromatin is normally packaged. By tracking down the fate of these heterochromatic RNAs, they revealed a new post-transcriptional mechanism of silencing in heterochromatin that involves the dynamic turnover of HP1Swi6 between its free, chromatin-bound and RNA-bound forms. The latter form escorts heterochromatic RNA to degradation. PMID:22705945

  17. User manual of the multicompenent variably - saturated flow and transport model HP1

    International Nuclear Information System (INIS)

    Jacques, D.; Simunek, J.

    2005-06-01

    This report describes a new comprehensive simulation tool HP1 (HYDRUS1D-PHREEQC) that was obtained by coupling the HYDRUS-1D one-dimensional variably-saturated water flow and solute transport model with the PHREEQC geochemical code. The HP1 code incorporates modules simulating (1) transient water flow in variably-saturated media, (2) transport of multiple components, and (3) mixed equilibrium/kinetic geochemical reactions. The program numerically solves the Richards equation for variably-saturated water flow and advection-dispersion type equations for heat and solute transport. The flow equation incorporates a sink term to account for water uptake by plant roots. The heat transport equation considers transport due to conduction and convection with flowing water. The solute transport equations consider advective-dispersive transport in the liquid phase. The program can simulate a broad range of low-temperature biogeochemical reactions in water, soil and ground water systems including interactions with minerals, gases, exchangers, and sorption surfaces, based on thermodynamic equilibrium, kinetics, or mixed equilibrium-kinetic reactions. The program may be used to analyze water and solute movement in unsaturated, partially saturated, or fully saturated porous media. The flow region may be composed of nonuniform soils or sediments. Flow and transport can occur in the vertical, horizontal, or a generally inclined direction. The water flow part of the model can deal with prescribed head and flux boundaries, boundaries controlled by atmospheric conditions, as well as free drainage boundary conditions. The governing flow and transport equations were solved numerically using Galerkin-type linear finite element schemes. To test the accuracy of the coupling procedures implemented in HP1, simulation results were compared with (i) HYDRUS-1D for transport problems of multiple components subject to sequential first-order decay, (ii) PHREEQC for steady-state flow conditions, and

  18. HP Ge planar detectors

    International Nuclear Information System (INIS)

    Gornov, M.G.; Gurov, Yu.B.; Soldatov, A.M.; Osipenko, B.P.; Yurkowski, J.; Podkopaev, O.I.

    1989-01-01

    Parameters of planar detectors manufactured of HP Ge are presented. The possibilities to use multilayer spectrometers on the base of such semiconductor detectors for nuclear physics experiments are discussed. It is shown that the obtained detectors including high square ones have spectrometrical characteristics close to limiting possible values. 9 refs.; 3 figs.; 1 tab

  19. Dampening or savoring positive emotions: a dialectical cultural script guides emotion regulation.

    Science.gov (United States)

    Miyamoto, Yuri; Ma, Xiaoming

    2011-12-01

    Four studies examined the hypothesis that, although people may generally want to savor, rather than to dampen, their positive emotions (i.e., hedonic emotion regulation), such a hedonic emotion regulation tendency should be less pronounced for Easterners than for Westerners. Using retrospective memory procedures, Study 1 found that Easterners recalled engaging in hedonic emotion regulation less than Westerners did, even after controlling for their initial emotional reactions. Studies 2-3 showed that cultural differences in emotion regulation were mediated by dialectical beliefs about positive emotions. Study 4 replicated the findings by examining online reports of emotion regulation strategies on the day students received a good grade. Furthermore, there were cultural differences in actual emotion change over time, which was partly explained by dialectical beliefs about positive emotions. These findings highlight the active role cultural scripts play in shaping emotion regulation and emotional experiences. (c) 2011 APA, all rights reserved.

  20. TaEDS1 genes positively regulate resistance to powdery mildew in wheat.

    Science.gov (United States)

    Chen, Guiping; Wei, Bo; Li, Guoliang; Gong, Caiyan; Fan, Renchun; Zhang, Xiangqi

    2018-04-01

    Three EDS1 genes were cloned from common wheat and were demonstrated to positively regulate resistance to powdery mildew in wheat. The EDS1 proteins play important roles in plant basal resistance and TIR-NB-LRR protein-triggered resistance in dicots. Until now, there have been very few studies on EDS1 in monocots, and none in wheat. Here, we report on three common wheat orthologous genes of EDS1 family (TaEDS1-5A, 5B and 5D) and their function in powdery mildew resistance. Comparisons of these genes with their orthologs in diploid ancestors revealed that EDS1 is a conserved gene family in Triticeae. The cDNA sequence similarity among the three TaEDS1 genes was greater than 96.5%, and they shared sequence similarities of more than 99.6% with the respective orthologs from diploid ancestors. The phylogenetic analysis revealed that the EDS1 family originated prior to the differentiation of monocots and dicots, and EDS1 members have since undergone clear structural differentiation. The transcriptional levels of TaEDS1 genes in the leaves were obviously higher than those of the other organs, and they were induced by Blumeria graminis f. sp. tritici (Bgt) infection and salicylic acid (SA) treatment. The BSMV-VIGS experiments indicated that knock-down the transcriptional levels of the TaEDS1 genes in a powdery mildew-resistant variety of common wheat compromised resistance. Contrarily, transient overexpression of TaEDS1 genes in a susceptible common wheat variety significantly reduced the haustorium index and attenuated the growth of Bgt. Furthermore, the expression of TaEDS1 genes in the Arabidopsis mutant eds1-1 complemented its susceptible phenotype to powdery mildew. The above evidences strongly suggest that TaEDS1 acts as a positive regulator and confers resistance against powdery mildew in common wheat.

  1. Informative gene selection using Adaptive Analytic Hierarchy Process (A2HP

    Directory of Open Access Journals (Sweden)

    Abhishek Bhola

    2017-12-01

    Full Text Available Gene expression dataset derived from microarray experiments are marked by large number of genes, which contains the gene expression values at different sample conditions/time-points. Selection of informative genes from these large datasets is an issue of major concern for various researchers and biologists. In this study, we propose a gene selection and dimensionality reduction method called Adaptive Analytic Hierarchy Process (A2HP. Traditional analytic hierarchy process is a multiple-criteria based decision analysis method whose result depends upon the expert knowledge or decision makers. It is mainly used to solve the decision problems in different fields. On the other hand, A2HP is a fused method that combines the outcomes of five individual gene selection ranking methods t-test, chi-square variance test, z-test, wilcoxon test and signal-to-noise ratio (SNR. At first, the preprocessing of gene expression dataset is done and then the reduced number of genes obtained, will be fed as input for A2HP. A2HP utilizes both quantitative and qualitative factors to select the informative genes. Results demonstrate that A2HP selects efficient number of genes as compared to the individual gene selection methods. The percentage of deduction in number of genes and time complexity are taken as the performance measure for the proposed method. And it is shown that A2HP outperforms individual gene selection methods.

  2. Acid Stability of the Hemagglutinin Protein Regulates H5N1 Influenza Virus Pathogenicity

    Energy Technology Data Exchange (ETDEWEB)

    DuBois, Rebecca M.; Zaraket, Hassan; Reddivari, Muralidhar; Heath, Richard J.; White, Stephen W.; Russell, Charles J. (Tennessee-HSC); (SJCH)

    2012-12-10

    Highly pathogenic avian influenza viruses of the H5N1 subtype continue to threaten agriculture and human health. Here, we use biochemistry and x-ray crystallography to reveal how amino-acid variations in the hemagglutinin (HA) protein contribute to the pathogenicity of H5N1 influenza virus in chickens. HA proteins from highly pathogenic (HP) A/chicken/Hong Kong/YU562/2001 and moderately pathogenic (MP) A/goose/Hong Kong/437-10/1999 isolates of H5N1 were found to be expressed and cleaved in similar amounts, and both proteins had similar receptor-binding properties. However, amino-acid variations at positions 104 and 115 in the vestigial esterase sub-domain of the HA1 receptor-binding domain (RBD) were found to modulate the pH of HA activation such that the HP and MP HA proteins are activated for membrane fusion at pH 5.7 and 5.3, respectively. In general, an increase in H5N1 pathogenicity in chickens was found to correlate with an increase in the pH of HA activation for mutant and chimeric HA proteins in the observed range of pH 5.2 to 6.0. We determined a crystal structure of the MP HA protein at 2.50 {angstrom} resolution and two structures of HP HA at 2.95 and 3.10 {angstrom} resolution. Residues 104 and 115 that modulate the acid stability of the HA protein are situated at the N- and C-termini of the 110-helix in the vestigial esterase sub-domain, which interacts with the B loop of the HA2 stalk domain. Interactions between the 110-helix and the stalk domain appear to be important in regulating HA protein acid stability, which in turn modulates influenza virus replication and pathogenesis. Overall, an optimal activation pH of the HA protein is found to be necessary for high pathogenicity by H5N1 influenza virus in avian species.

  3. Investigation of the three-dimensional lattice HP protein folding model using a genetic algorithm

    Directory of Open Access Journals (Sweden)

    Fábio L. Custódio

    2004-01-01

    Full Text Available An approach to the hydrophobic-polar (HP protein folding model was developed using a genetic algorithm (GA to find the optimal structures on a 3D cubic lattice. A modification was introduced to the scoring system of the original model to improve the model's capacity to generate more natural-like structures. The modification was based on the assumption that it may be preferable for a hydrophobic monomer to have a polar neighbor than to be in direct contact with the polar solvent. The compactness and the segregation criteria were used to compare structures created by the original HP model and by the modified one. An islands' algorithm, a new selection scheme and multiple-points crossover were used to improve the performance of the algorithm. Ten sequences, seven with length 27 and three with length 64 were analyzed. Our results suggest that the modified model has a greater tendency to form globular structures. This might be preferable, since the original HP model does not take into account the positioning of long polar segments. The algorithm was implemented in the form of a program with a graphical user interface that might have a didactical potential in the study of GA and on the understanding of hydrophobic core formation.

  4. HP investeerib tulevikku / Fredy-Edwin Esse

    Index Scriptorium Estoniae

    Esse, Fredy-Edwin

    2010-01-01

    Maailma suurima tehnoloogiafirma Hewlett-Packard (HP) tootearenduskulud kasvasid IV kvartalis 16%, 814 mln dollarini. Autor märgib, et HP aktsia on praegu väga hea saak, kuid mingit imehüpet aktsia hinnas ei tuleks kindlasti oodata

  5. miR-21-3p is a positive regulator of L1CAM in several human carcinomas.

    Science.gov (United States)

    Doberstein, Kai; Bretz, Niko P; Schirmer, Uwe; Fiegl, Heidi; Blaheta, Roman; Breunig, Christian; Müller-Holzner, Elisabeth; Reimer, Dan; Zeimet, Alain G; Altevogt, Peter

    2014-11-28

    Expression of L1 cell adhesion molecule (L1CAM) occurs frequently in human cancers and is associated with poor prognosis in cancers such as ovarian, endometrial, breast, renal cell carcinoma and pancreatic ductal adenocarcinoma. L1CAM promotes cell motility, invasion, chemoresistance and metastasis formation. Elucidating genetic processes involved in the expression of L1CAM in cancers is of considerable importance. Transcription factors such as SLUG, β-catenin/TCF-LEF, PAX8 and VHL have been implicated in the re-activation of L1CAM in various types of cancers. There is increasing evidence that micro-RNAs can also have strong effects on gene expression. Here we have identified miR-21-3p as a positive regulator of L1CAM expression. Over-expression of miR-21-3p (miR-21*) but not the complementary sequence miR-21-5p (miR-21) could strongly augment L1CAM expression in renal, endometrial and ovarian carcinoma derived cell lines by an unknown mechanism involving transcriptional activation of the L1CAM gene. In patient cohorts from renal, endometrial and ovarian cancers we observed a strong positive correlation of L1CAM and miR-21-3p expressions. Although L1CAM alone was a reliable marker for overall and disease free survival, the combination of L1CAM and miR-21-3p expressions strongly enhanced the predictive power. Our findings shed new light on the complex regulation of L1CAM in cancers and advocate the use of L1CAM/miR-21-3p for diagnostic application. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Positive Emotion Regulation and Psychopathology: A Transdiagnostic Cultural Neuroscience Approach

    Science.gov (United States)

    Hechtman, Lisa A.; Raila, Hannah; Chiao, Joan Y.; Gruber, June

    2013-01-01

    There is burgeoning interest in the study of positive emotion regulation and psychopathology. Given the significant public health costs and the tremendous variance in national prevalence rates associated with many disorders of positive emotion, it is critical to reach an understanding of how cultural factors, along with biological factors, mutually influence positive emotion regulation. Progress in this domain has been relatively unexplored, however, underscoring the need for an integrative review and empirical roadmap for investigating the cultural neuroscientific contributions to positive emotion disturbance for both affective and clinical science domains. The present paper thus provides a multidisciplinary, cultural neuroscience approach to better understand positive emotion regulation and psychopathology. We conclude with a future roadmap for researchers aimed at harnessing positive emotion and alleviating the burden of mental illness cross-culturally. PMID:24812583

  7. Positive sliding mode control for blood glucose regulation

    Science.gov (United States)

    Menani, Karima; Mohammadridha, Taghreed; Magdelaine, Nicolas; Abdelaziz, Mourad; Moog, Claude H.

    2017-11-01

    Biological systems involving positive variables as concentrations are some examples of so-called positive systems. This is the case of the glycemia-insulinemia system considered in this paper. To cope with these physical constraints, it is shown that a positive sliding mode control (SMC) can be designed for glycemia regulation. The largest positive invariant set (PIS) is obtained for the insulinemia subsystem in open and closed loop. The existence of a positive SMC for glycemia regulation is shown here for the first time. Necessary conditions to design the sliding surface and the discontinuity gain are derived to guarantee a positive SMC for the insulin dynamics. SMC is designed to be positive everywhere in the largest closed-loop PIS of plasma insulin system. Two-stage SMC is employed; the last stage SMC2 block uses the glycemia error to design the desired insulin trajectory. Then the plasma insulin state is forced to track the reference via SMC1. The resulting desired insulin trajectory is the required virtual control input of the glycemia system to eliminate blood glucose (BG) error. The positive control is tested in silico on type-1 diabetic patients model derived from real-life clinical data.

  8. Soybean (Glycine max) WRINKLED1 transcription factor, GmWRI1a, positively regulates seed oil accumulation.

    Science.gov (United States)

    Chen, Liang; Zheng, Yuhong; Dong, Zhimin; Meng, Fanfan; Sun, Xingmiao; Fan, Xuhong; Zhang, Yunfeng; Wang, Mingliang; Wang, Shuming

    2018-04-01

    Soybean is the world's most important leguminous crop producing high-quality protein and oil. Elevating oil accumulation in soybean seed is always many researchers' goal. WRINKLED1 (WRI1) encodes a transcription factor of the APETALA2/ethylene responsive element-binding protein (AP2/EREBP) family that plays important roles during plant seed oil accumulation. In this study, we isolated and characterized three distinct orthologues of WRI1 in soybean (Glycine max) that display different organ-specific expression patterns, among which GmWRI1a was highly expressed in maturing soybean seed. Electrophoretic mobility shift assays and yeast one-hybrid experiments demonstrated that the GmWRI1a protein was capable of binding to AW-box, a conserved sequence in the proximal upstream regions of many genes involved in various steps of oil biosynthesis. Transgenic soybean seeds overexpressing GmWRI1a under the control of the seed-specific napin promoter showed the increased total oil and fatty acid content and the changed fatty acid composition. Furthermore, basing on the activated expressions in transgenic soybean seeds and existence of AW-box element in the promoter regions, direct downstream genes of GmWRI1a were identified, and their products were responsible for fatty acid production, elongation, desaturation and export from plastid. We conclude that GmWRI1a transcription factor can positively regulate oil accumulation in soybean seed by a complex gene expression network related to fatty acid biosynthesis.

  9. New approach to calculate the true-coincidence effect of HpGe detector

    Energy Technology Data Exchange (ETDEWEB)

    Alnour, I. A., E-mail: aaibrahim3@live.utm.my, E-mail: ibrahim.elnour@yahoo.com [Department of Physics, Faculty of Pure and Applied Science, International University of Africa, 12223 Khartoum (Sudan); Wagiran, H. [Department of Physics, Faculty of Science, Universiti Teknologi Malaysia, 81310 UTM Skudai,Johor (Malaysia); Ibrahim, N. [Faculty of Defence Science and Technology, National Defence University of Malaysia, Kem Sungai Besi, 57000 Kuala Lumpur (Malaysia); Hamzah, S.; Elias, M. S. [Malaysia Nuclear Agency (MNA), Bangi, 43000 Kajang, Selangor D.E. (Malaysia); Siong, W. B. [Chemistry Department, Faculty of Resource Science & Technology, Universiti Malaysia Sarawak, 94300 Kota Samarahan, Sarawak (Malaysia)

    2016-01-22

    The corrections for true-coincidence effects in HpGe detector are important, especially at low source-to-detector distances. This work established an approach to calculate the true-coincidence effects experimentally for HpGe detectors of type Canberra GC3018 and Ortec GEM25-76-XLB-C, which are in operation at neutron activation analysis lab in Malaysian Nuclear Agency (NM). The correction for true-coincidence effects was performed close to detector at distances 2 and 5 cm using {sup 57}Co, {sup 60}Co, {sup 133}Ba and {sup 137}Cs as standard point sources. The correction factors were ranged between 0.93-1.10 at 2 cm and 0.97-1.00 at 5 cm for Canberra HpGe detector; whereas for Ortec HpGe detector ranged between 0.92-1.13 and 0.95-100 at 2 and 5 cm respectively. The change in efficiency calibration curve of the detector at 2 and 5 cm after correction was found to be less than 1%. Moreover, the polynomial parameters functions were simulated through a computer program, MATLAB in order to find an accurate fit to the experimental data points.

  10. Concurrent proinflammatory and apoptotic activity of a Helicobacter pylori protein (HP986 points to its role in chronic persistence.

    Directory of Open Access Journals (Sweden)

    Ayesha Alvi

    Full Text Available Helicobacter pylori induces cytokine mediated changes in gastroduodenal pathophysiology, wherein, the activated macrophages at the sub-mucosal space play a central role in mounting innate immune response against the antigens. The bacterium gains niche through persistent inflammation and local immune-suppression causing peptic ulcer disease or chronic gastritis; the latter being a significant risk factor for the development of gastric adenocarcinoma. What favors persistence of H. pylori in the gastric niches is not clearly understood. We report detailed characterization of a functionally unknown gene (HP986, which was detected in patient isolates associated with peptic ulcer and gastric carcinoma. Expression and purification of recombinant HP986 (rHP986 revealed a novel, ∼29 kDa protein in biologically active form which associates with significant levels of humoral immune responses in diseased individuals (p<0.001. Also, it induced significant levels of TNF-α and Interleukin-8 in cultured human macrophages concurrent to the translocation of nuclear transcription factor-κB (NF-κB. Further, the rHP986 induced apoptosis of cultured macrophages through a Fas mediated pathway. Dissection of the underlying signaling mechanism revealed that rHP986 induces both TNFR1 and Fas expression to lead to apoptosis. We further demonstrated interaction of HP986 with TNFR1 through computational and experimental approaches. Independent proinflammatory and apoptotic responses triggered by rHP986 as shown in this study point to its role, possibly as a survival strategy to gain niche through inflammation and to counter the activated macrophages to avoid clearance.

  11. The Grasso 5HP as a heat pump compressor for a dairy industry; De Grasso 5HP als warmtepompcompressor voor melkfabriek

    Energy Technology Data Exchange (ETDEWEB)

    Vermeer, H.; Gerritsen, J.; Unsworth, R. [Gea Grenco, Den Bosch (Netherlands)

    2011-12-15

    GEA Refrigeration has supplied a new cooling system with an additional stage heat pump to the milk factory Robert Wiseman for the pasteurisation of milk. The required condensation temperature of the additional stage heat pump is around 80C. The Grasso 5HP reciprocating compressor has a favorable energy consumption and can be used for this application. The limitation of this compressor, however, sets requirements to the design of the installation. [Dutch] Gea Refrigeration heeft een nieuwe koelinstallatie met extratrapwarmtepomp geleverd aan zuivelbedrijf Robert Wiseman ten behoeve van pasteuriseren van melk. De hiervoor benodigde condensatietemperatuur van de extratrapwarmtepomp bedraagt ongeveer 80C. De Grasso 5HP hogedrukzuigercompressor heeft een gunstig energiegebruik en kan voor deze toepassing ingezet worden. De begrenzing van het toepassingsgebied van deze compressor stelt echter eisen aan het ontwerp van de installatie.

  12. A socio-cultural instrumental approach to emotion regulation: Culture and the regulation of positive emotions.

    Science.gov (United States)

    Ma, Xiaoming; Tamir, Maya; Miyamoto, Yuri

    2018-02-01

    We propose a sociocultural instrumental approach to emotion regulation. According to this approach, cultural differences in the tendency to savor rather than dampen positive emotions should be more pronounced when people are actively pursuing goals (i.e., contexts requiring higher cognitive effort) than when they are not (i.e., contexts requiring lower cognitive efforts), because cultural beliefs about the utility of positive emotions should become most relevant when people are engaging in active goal pursuit. Four studies provided support for our theory. First, European Americans perceived more utility and less harm of positive emotions than Japanese did (Study 1). Second, European Americans reported a stronger relative preference for positive emotions than Asians, but this cultural difference was larger in high cognitive effort contexts than in moderate or low cognitive effort contexts (Study 2). Third, European Americans reported trying to savor rather than dampen positive emotions more than Asians did when preparing to take an exam, a typical high cognitive effort context (Studies 3-4), but these cultural differences were attenuated when an exam was not expected (Study 3) and disappeared when participants expected to interact with a stranger (Study 4). These findings suggest that cultural backgrounds and situational demands interact to shape how people regulate positive emotions. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  13. The silent information regulator 1 (Sirt1) is a positive regulator of the Notch pathway in Drosophila

    Czech Academy of Sciences Publication Activity Database

    Horváth, Matěj; Mihajlović, Zorana; Slaninová, Věra; Perez-Gomez, Raquel; Moshkin, Y.; Krejčí, Alena

    2016-01-01

    Roč. 473, č. 22 (2016), s. 4129-4143 ISSN 0264-6021 R&D Projects: GA ČR(CZ) GA14-08583S Institutional support: RVO:60077344 Keywords : Drosophila * silent information regulator 1 * Notch pathway Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.797, year: 2016

  14. AtPP2CG1, a protein phosphatase 2C, positively regulates salt tolerance of Arabidopsis in abscisic acid-dependent manner

    International Nuclear Information System (INIS)

    Liu, Xin; Zhu, Yanming; Zhai, Hong; Cai, Hua; Ji, Wei; Luo, Xiao; Li, Jing; Bai, Xi

    2012-01-01

    Highlights: ► AtPP2CG1 positively regulates salt tolerance in ABA-dependent manner. ► AtPP2CG1 up-regulates the expression of marker genes in different pathways. ► AtPP2CG1 expresses in the vascular system and trichomes of Arabidopsis. -- Abstract: AtPP2CG1 (Arabidopsis thaliana protein phosphatase 2C G Group 1) was predicted as an abiotic stress candidate gene by bioinformatic analysis in our previous study. The gene encodes a putative protein phosphatase 2C that belongs to Group G of PP2C. There is no report of Group G genes involved in abiotic stress so far. Real-time RT-PCR analysis showed that AtPP2CG1 expression was induced by salt, drought, and abscisic acid (ABA) treatment. The expression levels of AtPP2CG1 in the ABA synthesis-deficient mutant abi2–3 were much lower than that in WT plants under salt stress suggesting that the expression of AtPP2CG1 acts in an ABA-dependent manner. Over-expression of AtPP2CG1 led to enhanced salt tolerance, whereas its loss of function caused decreased salt tolerance. These results indicate that AtPP2CG1 positively regulates salt stress in an ABA-dependent manner. Under salt treatment, AtPP2CG1 up-regulated the expression levels of stress-responsive genes, including RD29A, RD29B, DREB2A and KIN1. GUS activity was detected in roots, leaves, stems, flower, and trichomes of AtPP2CG1 promoter–GUS transgenic plants. AtPP2CG1 protein was localized in nucleus and cytoplasm via AtPP2CG1:eGFP and YFP:AtPP2CG1 fusion approaches.

  15. AtPP2CG1, a protein phosphatase 2C, positively regulates salt tolerance of Arabidopsis in abscisic acid-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xin, E-mail: fangfei6073@126.com [Plant Bioengineering Laboratory, Northeast Agricultural University, Harbin 150030 (China); Zhu, Yanming, E-mail: ymzhu2001@neau.edu.cn [Plant Bioengineering Laboratory, Northeast Agricultural University, Harbin 150030 (China); Zhai, Hong, E-mail: Zhai.h@neigaehrb.ac.cn [Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Harbin 150040 (China); Cai, Hua, E-mail: small-big@sohu.com [Plant Bioengineering Laboratory, Northeast Agricultural University, Harbin 150030 (China); Ji, Wei, E-mail: iwei_j@hotmail.com [Plant Bioengineering Laboratory, Northeast Agricultural University, Harbin 150030 (China); Luo, Xiao, E-mail: luoxiao2010@yahoo.cn [Plant Bioengineering Laboratory, Northeast Agricultural University, Harbin 150030 (China); Li, Jing, E-mail: lijing@neau.edu.cn [Plant Secondary Metabolism Laboratory, Northeast Agricultural University, Harbin 150030 (China); Bai, Xi, E-mail: baixi@neau.edu.cn [Plant Bioengineering Laboratory, Northeast Agricultural University, Harbin 150030 (China)

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer AtPP2CG1 positively regulates salt tolerance in ABA-dependent manner. Black-Right-Pointing-Pointer AtPP2CG1 up-regulates the expression of marker genes in different pathways. Black-Right-Pointing-Pointer AtPP2CG1 expresses in the vascular system and trichomes of Arabidopsis. -- Abstract: AtPP2CG1 (Arabidopsis thaliana protein phosphatase 2C G Group 1) was predicted as an abiotic stress candidate gene by bioinformatic analysis in our previous study. The gene encodes a putative protein phosphatase 2C that belongs to Group G of PP2C. There is no report of Group G genes involved in abiotic stress so far. Real-time RT-PCR analysis showed that AtPP2CG1 expression was induced by salt, drought, and abscisic acid (ABA) treatment. The expression levels of AtPP2CG1 in the ABA synthesis-deficient mutant abi2-3 were much lower than that in WT plants under salt stress suggesting that the expression of AtPP2CG1 acts in an ABA-dependent manner. Over-expression of AtPP2CG1 led to enhanced salt tolerance, whereas its loss of function caused decreased salt tolerance. These results indicate that AtPP2CG1 positively regulates salt stress in an ABA-dependent manner. Under salt treatment, AtPP2CG1 up-regulated the expression levels of stress-responsive genes, including RD29A, RD29B, DREB2A and KIN1. GUS activity was detected in roots, leaves, stems, flower, and trichomes of AtPP2CG1 promoter-GUS transgenic plants. AtPP2CG1 protein was localized in nucleus and cytoplasm via AtPP2CG1:eGFP and YFP:AtPP2CG1 fusion approaches.

  16. Progression of Emphysema Evaluated by MRI Using Hyperpolarized 3He (HP 3He Measurements in Patients with Alpha-1-Antitrypsin (A1AT) Deficiency Compared with CT and Lung Function Tests

    International Nuclear Information System (INIS)

    Stavngaard, T.; Vejby Soegaard, L.; Batz, M.; Schreiber, L.M.; Dirksen, A.

    2009-01-01

    Background: The progression of emphysema is traditionally measured by pulmonary function test, with forced expiratory volume in 1 s (FEV1) being the most accepted and used measurement. However, FEV1 is insensitive in detecting mild/slow progression of emphysema because of low reproducibility as compared to yearly decline. Purpose: To investigate the progression of emphysema over a period of 2 years using diffusion-weighted hyperpolarized (HP) 3 He magnetic resonance imaging (MRI) in patients with alpha-1-antitrypsin (A1AT) deficiency. Material and Methods: Nine patients with severe A1AT deficiency were studied over a period of 2 years (baseline, year 1, and year 2) with HP 3 He MRI using apparent diffusion coefficient (ADC), lung function tests (FEV1 and carbon monoxide lung diffusion capacity [DL,CO]), and computed tomography (CT) using densitometric parameters (15th percentile density [CT-PD15] and relative area of emphysema below -910 HU [CT-RA-910]). Results: Seven patients were scanned three times, one patient two times, and one patient only at baseline. The mean increase in ADC values from first to last HP 3 He MR scanning was 3.8% (0.014 cm 2 /s [SD 0.024 cm 2 /s]; not significant). The time trends for FEV1, DL,CO, CT-PD15, and CT-RA-910 were all statistically significant. We found a high correlation between ADC and DL,CO (P 3 He MRI for monitoring the progression of emphysema. However, in the future, larger studies are needed to confirm these preliminary results

  17. Harsh parenting, child behavior problems, and the dynamic coupling of parents' and children's positive behaviors.

    Science.gov (United States)

    Lunkenheimer, Erika; Ram, Nilam; Skowron, Elizabeth A; Yin, Peifeng

    2017-09-01

    We examined self-reported maternal and paternal harsh parenting (HP) and its effect on the moment-to-moment dynamic coupling of maternal autonomy support and children's positive, autonomous behavior. This positive behavior coupling was measured via hidden Markov models as the likelihood of transitions into specific positive dyadic states in real time. We also examined whether positive behavior coupling, in turn, predicted later HP and child behavior problems. Children (N = 96; age = 3.5 years at Time 1) and mothers completed structured clean-up and puzzle tasks in the laboratory. Mothers' and fathers' HP was associated with children's being less likely to respond positively to maternal autonomy support; mothers' HP was also associated with mothers' being less likely to respond positively to children's autonomous behavior. When mothers responded to children's autonomous behavior with greater autonomy support, children showed fewer externalizing and internalizing problems over time and mothers showed less HP over time. These results were unique to the dynamic coupling of maternal autonomy support and children's autonomous behavior: The overall amount of these positive behaviors did not similarly predict reduced problems. Findings suggest that HP in the family system compromises the coregulation of positive behavior between mother and child and that improving mothers' and children's abilities to respond optimally to one another's autonomy-supportive behaviors may reduce HP and child behavior problems over time. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  18. A Chaotic Oscillator Based on HP Memristor Model

    Directory of Open Access Journals (Sweden)

    Guangyi Wang

    2015-01-01

    Full Text Available This paper proposes a simple autonomous memristor-based oscillator for generating periodic signals. Applying an external sinusoidal excitation to the autonomous system, a nonautonomous oscillator is obtained, which contains HP memristor model and four linear circuit elements. This memristor-based oscillator can generate periodic, chaotic, and hyperchaotic signals under the periodic excitation and an appropriate set of circuit parameters. It also shows that the system exhibits alternately a hidden attractor with no equilibrium and a self-excited attractor with a line equilibrium as time goes on. Furthermore, some specialties including burst chaos, irregular periodic bifurcations, and nonintermittence chaos of the circuit are found by theoretical analysis and numerical simulations. Finally, a discrete model for the HP memristor is given and the main statistical properties of this memristor-based oscillator are verified via DSP chip experiments and NIST (National Institute of Standards and Technology tests.

  19. HpBase: A genome database of a sea urchin, Hemicentrotus pulcherrimus.

    Science.gov (United States)

    Kinjo, Sonoko; Kiyomoto, Masato; Yamamoto, Takashi; Ikeo, Kazuho; Yaguchi, Shunsuke

    2018-04-01

    To understand the mystery of life, it is important to accumulate genomic information for various organisms because the whole genome encodes the commands for all the genes. Since the genome of Strongylocentrotus purpratus was sequenced in 2006 as the first sequenced genome in echinoderms, the genomic resources of other North American sea urchins have gradually been accumulated, but no sea urchin genomes are available in other areas, where many scientists have used the local species and reported important results. In this manuscript, we report a draft genome of the sea urchin Hemincentrotus pulcherrimus because this species has a long history as the target of developmental and cell biology in East Asia. The genome of H. pulcherrimus was assembled into 16,251 scaffold sequences with an N50 length of 143 kbp, and approximately 25,000 genes were identified in the genome. The size of the genome and the sequencing coverage were estimated to be approximately 800 Mbp and 100×, respectively. To provide these data and information of annotation, we constructed a database, HpBase (http://cell-innovation.nig.ac.jp/Hpul/). In HpBase, gene searches, genome browsing, and blast searches are available. In addition, HpBase includes the "recipes" for experiments from each lab using H. pulcherrimus. These recipes will continue to be updated according to the circumstances of individual scientists and can be powerful tools for experimental biologists and for the community. HpBase is a suitable dataset for evolutionary, developmental, and cell biologists to compare H. pulcherrimus genomic information with that of other species and to isolate gene information. © 2018 Japanese Society of Developmental Biologists.

  20. XAP5 CIRCADIAN TIMEKEEPER Positively Regulates RESISTANCE TO POWDERY MILDEW8.1–Mediated Immunity in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Yong-Ju Xu

    2017-11-01

    Full Text Available Ectopic expression of the Arabidopsis RESISTANCE TO POWDERY MILDEW8.1 (RPW8.1 boosts pattern-triggered immunity leading to enhanced resistance to different pathogens in Arabidopsis and rice. However, the underlying regulatory mechanism remains largely elusive. Here, we report that XAP5 CIRCADIAN TIMEKEEPER (XCT, At2g21150 positively regulates RPW8.1-mediated cell death and disease resistance. Forward genetic screen identified the b3-17 mutant that exhibited less cell death and susceptibility to powdery mildew and bacterial pathogens. Map-based cloning identified a G-to-A point mutation at the 3′ splice site of the 8th intron, which resulted in splice shift to 8-bp down-stream of the original splice site of XCT in b3-17, and introduced into a stop codon after two codons leading to a truncated XCT. XCT has previously been identified as a circadian clock gene required for small RNA biogenesis and acting down-stream of ETHYLENE-INSENSITIVE3 (EIN3 in the ethylene-signaling pathway. Here we further showed that mutation or down-regulation of XCT by artificial microRNA reduced RPW8.1-mediated immunity in R1Y4, a transgenic line expressing RPW8.1-YFP from the RPW8.1 native promoter. On the contrary, overexpression of XCT in R1Y4 background enhanced RPW8.1-mediated cell death, H2O2 production and resistance against powdery mildew. Consistently, the expression of RPW8.1 was down- and up-regulated in xct mutant and XCT overexpression lines, respectively. Taken together, these results indicate that XCT positively regulates RPW8.1-mediated cell death and disease resistance, and provide new insight into the regulatory mechanism of RPW8.1-mediated immunity.

  1. Progression of emphysema evaluated by MRI using hyperpolarized (3)He (HP (3)He) measurements in patients with alpha-1-antitrypsin (A1AT) deficiency compared with CT and lung function tests

    DEFF Research Database (Denmark)

    Stavngaard, T; Søgaard, L Vejby; Batz, M

    2009-01-01

    BACKGROUND: The progression of emphysema is traditionally measured by pulmonary function test, with forced expiratory volume in 1 s (FEV(1)) being the most accepted and used measurement. However, FEV(1) is insensitive in detecting mild/slow progression of emphysema because of low reproducibility...... as compared to yearly decline. PURPOSE: To investigate the progression of emphysema over a period of 2 years using diffusion-weighted hyperpolarized (HP) (3)He magnetic resonance imaging (MRI) in patients with alpha-1-antitrypsin (A1AT) deficiency. MATERIAL AND METHODS: Nine patients with severe A1AT...... density [CT-PD15] and relative area of emphysema below -910 HU [CT-RA-910]). RESULTS: Seven patients were scanned three times, one patient two times, and one patient only at baseline. The mean increase in ADC values from first to last HP (3)He MR scanning was 3.8% (0.014 cm(2)/s [SD 0.024 cm(2)/s...

  2. Positive academic emotions moderate the relationship between self-regulation and academic achievement.

    Science.gov (United States)

    Villavicencio, Felicidad T; Bernardo, Allan B I

    2013-06-01

    Research has shown how academic emotions are related to achievement and to cognitive/motivational variables that promote achievement. Mediated models have been proposed to account for the relationships among academic emotions, cognitive/motivational variables, and achievement, and research has supported such mediated models, particularly with negative emotions. The study tested the hypotheses: (1) self-regulation and the positive academic emotions of enjoyment and pride are positive predictors of achievement; and (2) enjoyment and pride both moderate the relationship between self-regulation and achievement. Participants were 1,345 students enrolled in various trigonometry classes in one university. Participants answered the Academic Emotions Questionnaire-Math (Pekrun, Goetz, & Frenzel, 2005) and a self-regulation scale (Pintrich, Smith, Garcia, & McKeachie, 1991) halfway through their trigonometry class. The students' final grades in the course were regressed to self-regulation, positive emotions, and the interaction terms to test the moderation effects. Enjoyment and pride were both positive predictors of grades; more importantly, both moderated the relationship between self-regulation and grades. For students who report higher levels of both positive emotions, self-regulation was positively associated with grades. However, for those who report lower levels of pride, self-regulation was not related to grades; and, for those who reported lower levels of enjoyment, self-regulation was negatively related to grades. The results are discussed in terms of how positive emotions indicate positive appraisals of task/outcome value, and thus enhance the positive links between cognitive/motivational variables and learning. ©2012 The British Psychological Society.

  3. Identification of nucleosome assembly protein 1 (NAP1) as an interacting partner of plant ribosomal protein S6 (RPS6) and a positive regulator of rDNA transcription

    Energy Technology Data Exchange (ETDEWEB)

    Son, Ora [Department of Biological Science, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Kim, Sunghan [Department of Biological Science, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Department of Plant Science, Plant Genomics and Breeding Institute, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 151-921 (Korea, Republic of); Shin, Yun-jeong [Department of Biological Science, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Kim, Woo-Young [College of Pharmacy, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Koh, Hee-Jong, E-mail: heejkoh@snu.ac.kr [Department of Plant Science, Plant Genomics and Breeding Institute, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 151-921 (Korea, Republic of); Cheon, Choong-Ill, E-mail: ccheon@sookmyung.ac.kr [Department of Biological Science, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of)

    2015-09-18

    The ribosomal protein S6 (RPS6) is a downstream component of the signaling mediated by the target of rapamycin (TOR) kinase that acts as a central regulator of the key metabolic processes, such as protein translation and ribosome biogenesis, in response to various environmental cues. In our previous study, we identified a novel role of plant RPS6, which negatively regulates rDNA transcription, forming a complex with a plant-specific histone deacetylase, AtHD2B. Here we report that the Arabidopsis RPS6 interacts additionally with a histone chaperone, nucleosome assembly protein 1(AtNAP1;1). The interaction does not appear to preclude the association of RPS6 with AtHD2B, as the AtNAP1 was also able to interact with AtHD2B as well as with an RPS6-AtHD2B fusion protein in the BiFC assay and pulldown experiment. Similar to a positive effect of the ribosomal S6 kinase 1 (AtS6K1) on rDNA transcription observed in this study, overexpression or down regulation of the AtNAP1;1 resulted in concomitant increase and decrease, respectively, in rDNA transcription suggesting a positive regulatory role played by AtNAP1 in plant rDNA transcription, possibly through derepression of the negative effect of the RPS6-AtHD2B complex. - Highlights: • Nucleosome assembly protein 1 (AtNAP1) interacts with RPS6 as well as with AtHD2B. • rDNA transcription is regulated S6K1. • Overexpression or down regulation of AtNAP1 results in concomitant increase or decrease in rDNA transcription.

  4. A comparative study of stool antigen Immunocard STAT HpSA test with biopsy in diagnosis of H Pylori Infection

    Directory of Open Access Journals (Sweden)

    Munish Rastogi

    2015-12-01

    Full Text Available The present study was conducted on 78 cases in the Department of Medicine at G.S.V.M Medical College, Kanpur who reported with various gastrointestinal symptoms such as dyspepsia, heartburns, nausea, vomiting and loss of appetite. They all were advised for biopsy by the physician. Patients treated with antibiotics, bismuth or proton pump inhibitors within 4 weeks preceding the study were excluded. Invasive tests using mucosal biopsies including histology and rapid urease test (RUT were used to establish the gold standard in order to evaluate the accuracy of Immunocard STAT HpSA. Sensitivity, Specificity, Positive Predictive Value and Negative Predictive Value of Immunocard STAT HpSA as compared to gold standard were 95.5%, 81.8%, 96.9% and 75.0% respectively. It is thus concluded that the Immunocard STAT HpSA test has a diagnostic value comparable to the gold standard in detecting H Pylori. The sensitivity and specificity of the test is fair enough to be used as a test for screening purpose and also for diagnosis and treatment of H.Pylori infection in clinical practice

  5. A replica exchange Monte Carlo algorithm for protein folding in the HP model

    Directory of Open Access Journals (Sweden)

    Shmygelska Alena

    2007-09-01

    Full Text Available Abstract Background The ab initio protein folding problem consists of predicting protein tertiary structure from a given amino acid sequence by minimizing an energy function; it is one of the most important and challenging problems in biochemistry, molecular biology and biophysics. The ab initio protein folding problem is computationally challenging and has been shown to be NP MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaat0uy0HwzTfgDPnwy1egaryqtHrhAL1wy0L2yHvdaiqaacqWFneVtcqqGqbauaaa@3961@-hard even when conformations are restricted to a lattice. In this work, we implement and evaluate the replica exchange Monte Carlo (REMC method, which has already been applied very successfully to more complex protein models and other optimization problems with complex energy landscapes, in combination with the highly effective pull move neighbourhood in two widely studied Hydrophobic Polar (HP lattice models. Results We demonstrate that REMC is highly effective for solving instances of the square (2D and cubic (3D HP protein folding problem. When using the pull move neighbourhood, REMC outperforms current state-of-the-art algorithms for most benchmark instances. Additionally, we show that this new algorithm provides a larger ensemble of ground-state structures than the existing state-of-the-art methods. Furthermore, it scales well with sequence length, and it finds significantly better conformations on long biological sequences and sequences with a provably unique ground-state structure, which is believed to be a characteristic of real proteins. We also present evidence that our REMC algorithm can fold sequences which exhibit significant interaction between termini in the hydrophobic core relatively easily. Conclusion We demonstrate that REMC utilizing the pull move

  6. Analyzing the soybean transcriptome during autoregulation of mycorrhization identifies the transcription factors GmNF-YA1a/b as positive regulators of arbuscular mycorrhization.

    Science.gov (United States)

    Schaarschmidt, Sara; Gresshoff, Peter M; Hause, Bettina

    2013-06-18

    Similarly to the legume-rhizobia symbiosis, the arbuscular mycorrhiza interaction is controlled by autoregulation representing a feedback inhibition involving the CLAVATA1-like receptor kinase NARK in shoots. However, little is known about signals and targets down-stream of NARK. To find NARK-related transcriptional changes in mycorrhizal soybean (Glycine max) plants, we analyzed wild-type and two nark mutant lines interacting with the arbuscular mycorrhiza fungus Rhizophagus irregularis. Affymetrix GeneChip analysis of non-inoculated and partially inoculated plants in a split-root system identified genes with potential regulation by arbuscular mycorrhiza or NARK. Most transcriptional changes occur locally during arbuscular mycorrhiza symbiosis and independently of NARK. RT-qPCR analysis verified nine genes as NARK-dependently regulated. Most of them have lower expression in roots or shoots of wild type compared to nark mutants, including genes encoding the receptor kinase GmSIK1, proteins with putative function as ornithine acetyl transferase, and a DEAD box RNA helicase. A predicted annexin named GmAnnx1a is differentially regulated by NARK and arbuscular mycorrhiza in distinct plant organs. Two putative CCAAT-binding transcription factor genes named GmNF-YA1a and GmNF-YA1b are down-regulated NARK-dependently in non-infected roots of mycorrhizal wild-type plants and functional gene analysis confirmed a positive role for these genes in the development of an arbuscular mycorrhiza symbiosis. Our results indicate GmNF-YA1a/b as positive regulators in arbuscular mycorrhiza establishment, whose expression is down-regulated by NARK in the autoregulated root tissue thereby diminishing subsequent infections. Genes regulated independently of arbuscular mycorrhization by NARK support an additional function of NARK in symbioses-independent mechanisms.

  7. DhHP-6 extends lifespan of Caenorhabditis elegans by enhancing nuclear translocation and transcriptional activity of DAF-16.

    Science.gov (United States)

    Huang, Lei; Li, Pengfei; Wang, Guan; Guan, Shuwen; Sun, Xiaoli; Wang, Liping

    2013-04-01

    Earlier studies have demonstrated that Deuterohaemin-AlaHisThrValGluLys (DhHP-6), a novel porphyrin-peptide, increases lifespan and enhances stress resistance of Caenorhabditis elegans. To explore the possible mechanisms, in this study we investigated the roles of SIR-2.1 and DAF-16 in DhHP-6's function using wild-type and various other mutant strains of C. elegans. DhHP-6's effect was dependent upon DAF-16, and it did not extend the lifespan of the loss-of-function daf-16 mutant strain (daf-16(mu86) I). DhHP-6 enhanced DAF-16 translocation from cytoplasm to nuclei; and it increased DAF-16's transcriptional activity, likely by activating the SIR-2.1/DAF-16 complex. DhHP-6's effect was also dependent upon SIR-2.1, and it did not increase the lifespan of the worms with SIR-2.1 deacetylase activity inhibited by niacin amide (SIR-2.1 inhibitor) and SIR-2.1 RNA interference (RNAi). Niacin amide and RNAi increased DAF-16's nuclear localization; but they decreased DAF-16's transcriptional activity, likely by preventing the formation of the SIR-2.1/DAF-16 complex. These results suggest that DhHP-6 extends the lifespan of C. elegans via SIR 2.1 and DAF-16, and they provide new insights into the molecular mechanisms of aging.

  8. Texture and structure contribution to low-temperature plasticity enhancement of Mg-Al-Zn-Mn Alloy MA2-1hp after ECAP and annealing

    Science.gov (United States)

    Serebryany, V. N.; D'yakonov, G. S.; Kopylov, V. I.; Salishchev, G. A.; Dobatkin, S. V.

    2013-05-01

    Equal channel angular pressing (ECAP) in magnesium alloys due to severe plastic shear deformations provides both grain refinement and the slope of the initial basal texture at 40°-50° to the pressing direction. These changes in microstructure and texture contribute to the improvement of low-temperature plasticity of the alloys. Quantitative texture X-ray diffraction analysis and diffraction of backscattered electrons are used to study the main textural and structural factors responsible for enhanced low-temperature plasticity based on the example of magnesium alloy MA2-1hp of the Mg-Al-Zn-Mn system. The possible mechanisms of deformation that lead to this positive effect are discussed.

  9. AaERF1 positively regulates the resistance to Botrytis cinerea in Artemisia annua.

    Directory of Open Access Journals (Sweden)

    Xu Lu

    Full Text Available Plants are sessile organisms, and they can not move away under abiotic or biotic stresses. Thus plants have evolved a set of genes that response to adverse environment to modulate gene expression. In this study, we characterized and functionally studied an ERF transcription factor from Artemisia annua, AaERF1, which plays an important role in biotic stress responses. The AaERF1 promoter had been cloned and GUS staining results of AaERF1 promoter-GUS transgenic A. annua showed that AaERF1 is expressed ubiquitiously in all organs. Several putative cis-acting elements such as W-box, TGA-box and Py-rich element, which are involved in defense responsiveness, are present in the promoter. The expression of AaERF1 can be induced vigorously by methyl jasmonate as well as by ethephon and wounding, implying that AaERF1 may activate some of the defense genes via the jasmonic acid and ethylene signaling pathways of A. annua. The results of electrophoretic mobility shift assay (EMSA and yeast one-hybrid experiments showed that AaERF1 was able to bind to the GCC box cis-acting element in vitro and in yeast. Ectopic expression of AaERF1 could enhance the expression levels of the defense marker genes PLANT DEFENSIN1.2 (PDF1.2 and BASIC CHITINASE (ChiB, and increase the resistance to Botrytis cinerea in the 35S::AaERF1 transgenic Arabidopsis. The down-regulated expression level of AaERF1 evidently reduced the resistance to B. cinerea in A. annua. The overall results showed that AaERF1 positively regulated the resistance to B. cinerea in A. annua.

  10. Discrete Maximum Principle for a 1D Problem with Piecewise-Constant Coefficients Solved by hp-FEM

    Czech Academy of Sciences Publication Activity Database

    Vejchodský, Tomáš; Šolín, Pavel

    2007-01-01

    Roč. 15, č. 3 (2007), s. 233-243 ISSN 1570-2820 R&D Projects: GA ČR GP201/04/P021; GA ČR GA102/05/0629 Institutional research plan: CEZ:AV0Z10190503; CEZ:AV0Z20570509 Keywords : discrete maximum principle * hp-FEM * Poisson equation Subject RIV: BA - General Mathematics

  11. TOR complex 2-Ypk1 signaling is an essential positive regulator of the general amino acid control response and autophagy.

    Science.gov (United States)

    Vlahakis, Ariadne; Graef, Martin; Nunnari, Jodi; Powers, Ted

    2014-07-22

    The highly conserved Target of Rapamycin (TOR) kinase is a central regulator of cell growth and metabolism in response to nutrient availability. TOR functions in two structurally and functionally distinct complexes, TOR Complex 1 (TORC1) and TOR Complex 2 (TORC2). Through TORC1, TOR negatively regulates autophagy, a conserved process that functions in quality control and cellular homeostasis and, in this capacity, is part of an adaptive nutrient deprivation response. Here we demonstrate that during amino acid starvation TOR also operates independently as a positive regulator of autophagy through the conserved TORC2 and its downstream target protein kinase, Ypk1. Under these conditions, TORC2-Ypk1 signaling negatively regulates the Ca(2+)/calmodulin-dependent phosphatase, calcineurin, to enable the activation of the amino acid-sensing eIF2α kinase, Gcn2, and to promote autophagy. Our work reveals that the TORC2 pathway regulates autophagy in an opposing manner to TORC1 to provide a tunable response to cellular metabolic status.

  12. Optimization of statistical methods for HpGe gamma-ray spectrometer used in wide count rate ranges

    Energy Technology Data Exchange (ETDEWEB)

    Gervino, G., E-mail: gervino@to.infn.it [UNITO - Università di Torino, Dipartimento di Fisica, Turin (Italy); INFN - Istituto Nazionale di Fisica Nucleare, Sez. Torino, Turin (Italy); Mana, G. [INRIM - Istituto Nazionale di Ricerca Metrologica, Turin (Italy); Palmisano, C. [UNITO - Università di Torino, Dipartimento di Fisica, Turin (Italy); INRIM - Istituto Nazionale di Ricerca Metrologica, Turin (Italy)

    2016-07-11

    The need to perform γ-ray measurements with HpGe detectors is a common technique in many fields such as nuclear physics, radiochemistry, nuclear medicine and neutron activation analysis. The use of HpGe detectors is chosen in situations where isotope identification is needed because of their excellent resolution. Our challenge is to obtain the “best” spectroscopy data possible in every measurement situation. “Best” is a combination of statistical (number of counts) and spectral quality (peak, width and position) over a wide range of counting rates. In this framework, we applied Bayesian methods and the Ellipsoidal Nested Sampling (a multidimensional integration technique) to study the most likely distribution for the shape of HpGe spectra. In treating these experiments, the prior information suggests to model the likelihood function with a product of Poisson distributions. We present the efforts that have been done in order to optimize the statistical methods to HpGe detector outputs with the aim to evaluate to a better order of precision the detector efficiency, the absolute measured activity and the spectra background. Reaching a more precise knowledge of statistical and systematic uncertainties for the measured physical observables is the final goal of this research project.

  13. The power of extraverts: testing positive and negative mood regulation

    Directory of Open Access Journals (Sweden)

    Gonzalo Hervas

    Full Text Available Extraversion is a personality trait which has been systematically related to positive affect and well-being. One of the mechanisms that may account for these positive outcomes is the ability to regulate the responses to positive, as well as negative, moods. Prior research has found that extraverts' higher positive mood maintenance could explain their higher levels of positive affect. However, research exploring differences between extraverts and introverts in negative mood regulation has yielded mixed results. The aim of the current study was explore the role of different facets of mood regulation displayed by extraverts, ambiverts, and introverts. After been exposed to a sad vs. happy mood induction, participants underwent a mood regulation task. Extraverts and ambiverts exhibited higher positive mood regulation than introverts, but similar mood repair. Thus, this research highlights the importance of positive mood regulation in the psychological functioning of extraverts, and opens new conceptualizations for developing interventions for introverts to improve their positive mood regulation and, hence, overall positive affect and well-being.

  14. Global regulation of robots using only position measurements

    NARCIS (Netherlands)

    Berghuis, Harry; Berghuis, Harry; Nijmeijer, Henk

    1993-01-01

    In this note we propose a simple solution to the regulation problem of rigid robots based on the availability of only joint position measurements. The controller consists of two parts: (1) a gravitation compensation, (2) a linear dynamic first-order compensator. The gravitation compensation part can

  15. Longitudinal study of self-regulation, positive parenting, and adjustment problems among physically abused children

    Science.gov (United States)

    Kim, Jungmeen; Haskett, Mary E.; Longo, Gregory S.; Nice, Rachel

    2012-01-01

    Objective Research using normative and high-risk samples indicates a significant link between problems with self-regulation and child maladjustment. Nevertheless, little is known about the processes that may modify the link between self-regulation and maladjustment. This longitudinal study examined the joint contributions of child self-regulation and positive parenting behaviors to the development of externalizing and internalizing symptomatology spanning from preschool to 1st grade. Methods Data were collected on a total of 95 physically abused children (58% boys); our longitudinal analyses involved 43 children at Time 1 (preschool), 63 children at Time 2 (kindergarten), and 54 children at Time 3 (1st grade). Children's self-regulation was measured by parent report, and their externalizing and internalizing symptomatology was evaluated by teachers. Parents completed self-report measures of positive parenting. Results Our structural equation modeling analyses revealed positive parenting as a protective factor that attenuated the concurrent association between low self-regulation and externalizing symptomatology among physically abused children. Our findings regarding longitudinal changes in children's externalizing symptomatology supported the differential susceptibility hypothesis: Physically abused children who were at greater risk due to low levels of self-regulation were more susceptible to the beneficial effects of positive parenting, compared to those with high levels of self-regulation. Conclusions Findings suggest that although physical abuse presents formidable challenges that interfere with the development of adaptive self-regulation, positive parenting behaviors may ameliorate the detrimental effects of maladaptive self-regulation on the development of externalizing symptomatology. In addition, the positive and negative effects of caregiving behaviors were more prominent among physically abused children at great risk due to low self-regulation. Practice

  16. DAMT - DISTRIBUTED APPLICATION MONITOR TOOL (HP9000 VERSION)

    Science.gov (United States)

    Keith, B.

    1994-01-01

    requires 1Mb of disk space and 4Mb of RAM for execution. This package requires MIT's X Window System, Version 11 Revision 4, with OSF/Motif 1.1. The HP-9000 version (GSC-13589) includes sample HP-9000/375 and HP-9000/730 executables which were compiled under HP-UX, and the Sun version (GSC-13559) includes sample Sun3 and Sun4 executables compiled under SunOS. The standard distribution medium for the HP version of DAMT is a .25 inch HP pre-formatted streaming magnetic tape cartridge in UNIX tar format. It is also available on a 4mm magnetic tape in UNIX tar format. The standard distribution medium for the Sun version of DAMT is a .25 inch streaming magnetic tape cartridge in UNIX tar format. It is also available on a 3.5 inch diskette in UNIX tar format. DAMT was developed in 1992.

  17. Prevalence of coagulase-positive staphylococci, other than Staphylococcus aureus, in bovine mastitis.

    Science.gov (United States)

    Roberson, J R; Fox, L K; Hancock, D D; Gay, J M; Besser, T E

    1996-01-01

    To determine prevalence and relevance of coagulase-positive Staphylococcus hyicus and S intermedius intramammary infections (IMI) in dairy cows and determine the ability of the 4-hour tube coagulase (TC) test to differentiate the coagulase-positive staphylococci (CPS). Prevalence of CPS was determined for primiparous cows (point prevalence and prevalence at first parturition) and multiparous cows (point prevalence) of 2 herd groups: 10% CPS IMI prevalence = high prevalence (HP). For prevalence, cows of 22 dairy herds. For TC, 1,038 CPS strains isolated from cow milk. Speciation of CPS from aseptically collected composite milk samples was performed. Coagulase-positive isolates from 4 cow groups were tested for their ability to coagulate rabbit plasma by 4 hours: LP and HP primiparous cows at parturition, and LP and HP cows any time after first parturition. Of 487 CPS in the prevalence study, 82.1% were S aureus, 17.7% were coagulase-positive S hyicus, and 0.2% were S intermedius. Of all CPS IMI in LP herds, 34% were coagulase-positive S hyicus; of all CPS IMI in HP herds, 9% were coagulase-positive S hyicus. Coagulase-positive S hyicus appeared to persist to the end of lactation in 4 cows (mean linear somatic cell count = 3.7). The TC test was > or = 97% sensitive, < or = 33% specific, and had a predictive value positive range of 60 to 97% for S aureus isolates. Coagulase-positive S hyicus appears capable of inducing chronic, low-grade IMI. Staphylococcus intermedius does not appear to be an important mastitis pathogen. The TC test is not valid to use as the sole method to differentiate CPS species.

  18. 175Hp contrarotating homopolar motor design report

    Science.gov (United States)

    Cannell, Michael J.; Drake, John L.; McConnell, Richard A.; Martino, William R.

    1994-06-01

    A normally conducting contrarotating homopolar motor has been designed and constructed. The reaction torque, in the outer rotor, from the inner rotor is utilized to produce true contrarotation. The machine utilizes liquid cooled conductors, high performance liquid metal current collectors, and ferrous conductors in the active region. The basic machine output is 175 hp at + or - 1,200 rpm with an input of 4 volts and 35,000 amps.

  19. Determination of the dose equivalent Hp(0.07) in hands of occupationally exposed personnel in the practice of proton emission tomography (PET/CT); Determinacion de la dosis equivalente Hp(0.07) en manos de trabajadores ocupacionalmente expuestos en la practica de Tomografia por Emision de Positrones (PET/CT)

    Energy Technology Data Exchange (ETDEWEB)

    Lea, D. [Servicio de Radiofisica Sanitaria, Unidad de Tecnologia Nuclear, Instituto Venezolano de Investigaciones Cientificas, Ministerio de Ciencia y Tecnologia, Km 11 Carretera Panamerican, Altos del Pipe, Caracas (Venezuela); Ruiz, N.; Esteves, L. [Centro Diagnostico Docente Las Mercedes, Calle Paris cruce con calle Caroni, Edif. CDD, Las Mercedes, Caracas (Venezuela)]. e-mail: dlea@ivic.ve

    2006-07-01

    In Venezuela recently it was implanted the Positron Emission Tomography technique (PET) with the perspective of implanting it at national level. Even when in our country practices it of nuclear medicine it exists from early of 70, there is not experience in the determination of the occupational doses by exposure to the external radiation in hands. By this reason, a concern exists in the workers of the centers of nuclear medicine where it is practiced the Positron Emission Tomography technique. In absence of the TLD dosimetry to measure dose in hands in our country, measurements of the dose equivalent of the workers of the PET national reference center were made, using a detector of hands type diode. It was determined the dose in hands in terms of dose equivalent Hp(0.07) in two work positions, that is: the corresponding to the transfer of the receiving vial of ({sup 18}F) FDG to the shield, quality control and uni doses division. The second work position corresponds the person in charge of administering, via intravenous, the ({sup 18}F) FDG. In this work it realizes the dose equivalent in hands Hp(0.07) measures in each one of the work positions before described by daily production. The informed doses correspond to a total average produced activity of 20.4 GBq (550 mCi). The results of the measurements in terms of dose equivalent in hands Hp(0.07) correspond to 2.1 {+-} 20% mSv in the work position of division and 0.4 {+-} 10% mSv in the position of injection of the radioactive material. At short term this foreseen until 4 productions per week, what means an annual dose equivalent Hp(0.07) in hands of 400 mSv approximately, without taking into account abnormal situations as its are spills of the ({sup 18}F) FDG in the work place. This work is the starting point so that the regulatory authority settles down, in Venezuela, dose restrictions in the PET practices and implant, in the centers of nuclear medicine, an optimization politics of this practice in conformity

  20. Triptolide inhibits proliferation of Epstein–Barr virus-positive B lymphocytes by down-regulating expression of a viral protein LMP1

    International Nuclear Information System (INIS)

    Zhou, Heng; Guo, Wei; Long, Cong; Wang, Huan; Wang, Jingchao; Sun, Xiaoping

    2015-01-01

    Highlights: • Triptolide inhibits proliferation of EBV-positive lymphoma cells in vitro and in vivo. • Triptolide reduces expression of LMP1 by decreasing its transcription level. • Triptolide inhibits ED-L1 promoter activity. - Abstract: Epstein–Barr virus (EBV) infects various types of cells and mainly establishes latent infection in B lymphocytes. The viral latent membrane protein 1 (LMP1) plays important roles in transformation and proliferation of B lymphocytes infected with EBV. Triptolide is a compound of Tripterygium extracts, showing anti-inflammatory, immunosuppressive, and anti-cancer activities. In this study, it is determined whether triptolide inhibits proliferation of Epstein–Barr virus-positive B lymphocytes. The CCK-8 assays were performed to examine cell viabilities of EBV-positive B95-8 and P3HR-1 cells treated by triptolide. The mRNA and protein levels of LMP1 were examined by real time-PCR and Western blotting, respectively. The activities of two LMP1 promoters (ED-L1 and TR-L1) were determined by Dual luciferase reportor assay. The results showed that triptolide inhibited the cell viability of EBV-positive B lymphocytes, and the over-expression of LMP1 attenuated this inhibitory effect. Triptolide decreased the LMP1 expression and transcriptional levels in EBV-positive B cells. The activity of LMP1 promoter ED-L1 in type III latent infection was strongly suppressed by triptolide treatment. In addition, triptolide strongly reduced growth of B95-8 induced B lymphoma in BALB/c nude mice. These results suggest that triptolide decreases proliferation of EBV-induced B lymphocytes possibly by a mechanism related to down-regulation of the LMP1 expression

  1. Triptolide inhibits proliferation of Epstein–Barr virus-positive B lymphocytes by down-regulating expression of a viral protein LMP1

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Heng [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Guo, Wei [Department of Pathology and Physiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Long, Cong; Wang, Huan; Wang, Jingchao [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Sun, Xiaoping, E-mail: xsun6@whu.edu.cn [Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); State Key Laboratory of Virology, Wuhan University, Wuhan 430072 (China)

    2015-01-16

    Highlights: • Triptolide inhibits proliferation of EBV-positive lymphoma cells in vitro and in vivo. • Triptolide reduces expression of LMP1 by decreasing its transcription level. • Triptolide inhibits ED-L1 promoter activity. - Abstract: Epstein–Barr virus (EBV) infects various types of cells and mainly establishes latent infection in B lymphocytes. The viral latent membrane protein 1 (LMP1) plays important roles in transformation and proliferation of B lymphocytes infected with EBV. Triptolide is a compound of Tripterygium extracts, showing anti-inflammatory, immunosuppressive, and anti-cancer activities. In this study, it is determined whether triptolide inhibits proliferation of Epstein–Barr virus-positive B lymphocytes. The CCK-8 assays were performed to examine cell viabilities of EBV-positive B95-8 and P3HR-1 cells treated by triptolide. The mRNA and protein levels of LMP1 were examined by real time-PCR and Western blotting, respectively. The activities of two LMP1 promoters (ED-L1 and TR-L1) were determined by Dual luciferase reportor assay. The results showed that triptolide inhibited the cell viability of EBV-positive B lymphocytes, and the over-expression of LMP1 attenuated this inhibitory effect. Triptolide decreased the LMP1 expression and transcriptional levels in EBV-positive B cells. The activity of LMP1 promoter ED-L1 in type III latent infection was strongly suppressed by triptolide treatment. In addition, triptolide strongly reduced growth of B95-8 induced B lymphoma in BALB/c nude mice. These results suggest that triptolide decreases proliferation of EBV-induced B lymphocytes possibly by a mechanism related to down-regulation of the LMP1 expression.

  2. Investigating tumor perfusion and metabolism using multiple hyperpolarized 13C compounds: HP001, pyruvate and urea

    DEFF Research Database (Denmark)

    von Morze, Cornelius; Larson, Peder E.Z.; Hu, Simon

    2012-01-01

    The metabolically inactive hyperpolarized agents HP001 (bis-1,1-(hydroxymethyl)-[1-13C]cyclopropane-d8) and urea enable a new type of perfusion magnetic resonance imaging based on a direct signal source that is background-free. The addition of perfusion information to metabolic information obtained...... (T1=95 s ex vivo, 32 s in vivo at 3 T) using a pulse sequence with balanced steady-state free precession and ramped flip angle over time for efficient utilization of the hyperpolarized magnetization and three-dimensional echo-planar spectroscopic imaging of urea copolarized with [1-13C...... of separate dynamic HP001 imaging and copolarized pyruvate/urea imaging were compared. A strong and significant correlation (R=0.73, P=.02) detected between the urea and HP001 data confirmed the value of copolarizing urea with pyruvate for simultaneous assessment of perfusion and metabolism....

  3. A sensitization effect of hematoporphyrin oligomer (HpO) and caffeine for X-ray radiation of skin cancer

    International Nuclear Information System (INIS)

    Ishiguro, Kazumori; Ueda, Keiichi; Miyoshi, Norio; Nakanishi, Kazuo; Fukuda, Masaru

    1990-01-01

    Human malignant melanoma cells (G-361) were irradiated with X-ray for different irradiation times. The amount of DNA damage was much increased by the treatment of the cells with hematoporphyrin oligomer (HpO) before X-ray irradiation. Furthermore, it was found that the caffeine inhibited effectively the repair of the damaged DNA. Furthermore, HpO was administered before X-ray irradiation of transplantable skin tumor in C3H mice and/or caffeine was to be given the mouse after X-ray irradiation. The growth of the irradiated tumor combined with HpO and/or caffeine was more inhibited, and the necrotic area was more expanded than that of the tumor irradiated with X-ray only. Labeling Index utilizing bromodeoxyuridine (BrdU) in the viable area of the treated tumor decreased when HpO and/or caffeine were administered. The amount of DNA damage more increased in the irradiated tumor cells given HpO than the only irradiated cells. And, the repair of the damaged DNA was more delayed in the irradiated tumor cells combined with HpO and caffeine than those with other treatments. In conclusion, it was considered that HpO might be a radioactive sensitizer and caffeine enhanced the inhibition of the repair of DNA damaged. We hope that the treatment of X-ray radiation combined with HpO and caffeine is useful for clinical treatment of human malignant tumor. (author) 54 refs

  4. A sensitization effect of hematoporphyrin oligomer (HpO) and caffeine for X-ray radiation of skin cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ishiguro, Kazumori; Ueda, Keiichi; Miyoshi, Norio; Nakanishi, Kazuo; Fukuda, Masaru (Fukui Medical School, Matsuoka (Japan))

    1990-05-01

    Human malignant melanoma cells (G-361) were irradiated with X-ray for different irradiation times. The amount of DNA damage was much increased by the treatment of the cells with hematoporphyrin oligomer (HpO) before X-ray irradiation. Furthermore, it was found that the caffeine inhibited effectively the repair of the damaged DNA. Furthermore, HpO was administered before X-ray irradiation of transplantable skin tumor in C3H mice and/or caffeine was to be given the mouse after X-ray irradiation. The growth of the irradiated tumor combined with HpO and/or caffeine was more inhibited, and the necrotic area was more expanded than that of the tumor irradiated with X-ray only. Labeling Index utilizing bromodeoxyuridine (BrdU) in the viable area of the treated tumor decreased when HpO and/or caffeine were administered. The amount of DNA damage more increased in the irradiated tumor cells given HpO than the only irradiated cells. And, the repair of the damaged DNA was more delayed in the irradiated tumor cells combined with HpO and caffeine than those with other treatments. In conclusion, it was considered that HpO might be a radioactive sensitizer and caffeine enhanced the inhibition of the repair of DNA damaged. We hope that the treatment of X-ray radiation combined with HpO and caffeine is useful for clinical treatment of human malignant tumor. (author) 54 refs.

  5. Optimal design of PV and HP system

    DEFF Research Database (Denmark)

    Nepper-Rasmussen, Bjarke Christian; Rasmussen, Theis Bo

    2015-01-01

    Methods of utilizing residential produced photovoltaic (PV) power by converting to thermal energy through heat pumps (HP) are present in literature, where thermal energy is dispersed as either heat or hot water at the instant moment of PV production. In this paper an alternative solution is descr...... that the thermal storage with a BT is a better investment than a PV system without HP or no investment. Furthermore, it showed that the optimization model developed in this project is capable of finding the optimal combination of component sizes based on our data.......Methods of utilizing residential produced photovoltaic (PV) power by converting to thermal energy through heat pumps (HP) are present in literature, where thermal energy is dispersed as either heat or hot water at the instant moment of PV production. In this paper an alternative solution...... is described, where the thermal energy is stored in a buffer tank (BT) capable of dispersing heat to either the heating system of a house or a hot water tank, for later use. The thermal storage solution including a BT can increase the self-consumption of residentially produced PV power and thereby shift...

  6. Tomato NAC transcription factor SlSRN1 positively regulates defense response against biotic stress but negatively regulates abiotic stress response.

    Directory of Open Access Journals (Sweden)

    Bo Liu

    Full Text Available Biotic and abiotic stresses are major unfavorable factors that affect crop productivity worldwide. NAC proteins comprise a large family of transcription factors that play important roles in plant growth and development as well as in responses to biotic and abiotic stresses. In a virus-induced gene silencing-based screening to identify genes that are involved in defense response against Botrytis cinerea, we identified a tomato NAC gene SlSRN1 (Solanum lycopersicum Stress-related NAC1. SlSRN1 is a plasma membrane-localized protein with transactivation activity in yeast. Expression of SlSRN1 was significantly induced by infection with B. cinerea or Pseudomonas syringae pv. tomato (Pst DC3000, leading to 6-8 folds higher than that in the mock-inoculated plants. Expression of SlSRN1 was also induced by salicylic acid, jasmonic acid and 1-amino cyclopropane-1-carboxylic acid and by drought stress. Silencing of SlSRN1 resulted in increased severity of diseases caused by B. cinerea and Pst DC3000. However, silencing of SlSRN1 resulted in increased tolerance against oxidative and drought stresses. Furthermore, silencing of SlSRN1 accelerated accumulation of reactive oxygen species but attenuated expression of defense genes after infection by B. cinerea. Our results demonstrate that SlSRN1 is a positive regulator of defense response against B. cinerea and Pst DC3000 but is a negative regulator for oxidative and drought stress response in tomato.

  7. p32, a novel binding partner of Mcl-1, positively regulates mitochondrial Ca{sup 2+} uptake and apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Kang [Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong (China); Wang, Yinyin; Chang, Zhijie [School of Medicine, Tsinghua University, Beijing (China); Lao, Yuanzhi, E-mail: laurence_ylao@163.com [School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai (China); Chang, Donald C., E-mail: bochang@ust.hk [Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong (China)

    2014-08-22

    Highlights: • p32 binds to Mcl-1. • p32 affects apoptosis. • p32 and Mcl-1 regulate mitochondrial Ca{sup 2+}. - Abstract: Mcl-1 is a major anti-apoptotic Bcl-2 family protein. It is well known that Mcl-1 can interact with certain pro-apoptotic Bcl-2 family proteins in normal cells to neutralize their pro-apoptotic functions, thus prevent apoptosis. In addition, it was recently found that Mcl-1 can also inhibit mitochondrial calcium uptake. The detailed mechanism, however, is still not clear. Based on Yeast Two-Hybrid screening and co-immunoprecipitation, we identified a mitochondrial protein p32 (C1qbp) as a novel binding partner of Mcl-1. We found that p32 had a number of interesting properties: (1) p32 can positively regulate UV-induced apoptosis in HeLa cells. (2) Over-expressing p32 could significantly promote mitochondrial calcium uptake, while silencing p32 by siRNA suppressed it. (3) In p32 knockdown cells, Ruthenium Red treatment (an inhibitor of mitochondrial calcium uniporter) showed no further suppressive effect on mitochondrial calcium uptake. In addition, in Ruthenium Red treated cells, Mcl-1 also failed to suppress mitochondrial calcium uptake. Taken together, our findings suggest that p32 is part of the putative mitochondrial uniporter that facilitates mitochondrial calcium uptake. By binding to p32, Mcl-1 can interfere with the uniporter function, thus inhibit the mitochondrial Ca{sup 2+} uploading. This may provide a novel mechanism to explain the anti-apoptotic function of Mcl-1.

  8. Comparison of gadolinium Cy2DOTA, a new hepatobiliary agent, and gadolinium HP-DO3A, an extracellular agent, in healthy liver and metastatic disease

    International Nuclear Information System (INIS)

    Runge, V.M.; Wells, J.W.; Williams, N.M.

    1995-01-01

    A new gadolinium (Gd) chelate with preferential hepatobiliary uptake, Gd Cy 2 DOTA, was compared in two animal species with Gd HP-DO3A (gadoteridol), a clinically approved contrast agent with extracellular distribution. Liver enhancement was evaluated for these two contrast agents using magnetic resonance imaging, whereas an experimental model of metastatic disease was used to evaluate the agents' efficacy for liver-lesion delineation. The two agents were compared in four healthy Rhesus monkeys (eight studies) and five New Zealand White rabbits with implanted VX-2 liver tumors (ten studies). The contrast dose was 0.1 mmol/kg, with the agents given in random order and at least 72 hours between contrast injections. Breathhold T1-weighted spin echo scans were obtained at 1.5 tesla (T) before and after contrast was administered. Postcontrast scans were obtained 1 to 90 minutes after injection in the monkeys and 1 to 240 minutes after injection in the rabbits. Prolonged hepatic enhancement, superior in degree to that with Gd HP-DO3A, was noted to both monkeys and rabbits after injection of Gd Cy 2 DOTA. Two minutes after contrast, liver SI was 1.94 ± 0.05 with Gd Cy 2 DOTA compared with 1.5 ± 0.05 with Gd HP-DO3A in monkeys. Sixty minutes after contrast, liver SI was 1.60 ± 0.09 compared with 1.20 ± 0.02. The difference between agents was significant at all times from 2 to 60 minutes after contrast injection (P 2 DOTA but not with Gd HP-DO3A. The maximum improvement in lesion conspicuity (rabbit) occurred 45 minutes after injection of Gd Cy 2 DOTA and 5 minutes after injection of Gd HP-DO3A. 22 refs., 12 figs

  9. VLBA DETERMINATION OF THE DISTANCE TO NEARBY STAR-FORMING REGIONS. III. HP TAU/G2 AND THE THREE-DIMENSIONAL STRUCTURE OF TAURUS

    International Nuclear Information System (INIS)

    Torres, Rosa M.; Loinard, Laurent; Rodriguez, Luis F.; Mioduszewski, Amy J.

    2009-01-01

    Using multiepoch Very Long Baseline Array (VLBA) observations, we have measured the trigonometric parallax of the weak-line T Tauri star HP Tau/G2 in Taurus. The best fit yields a distance of 161.2 ± 0.9 pc, suggesting that the eastern portion of Taurus (where HP Tau/G2 is located) corresponds to the far side of the complex. Previous VLBA observations have shown that T Tau, to the south of the complex, is at an intermediate distance of about 147 pc, whereas the region around L1495 corresponds to the near side at roughly 130 pc. Our observations of only four sources are still too coarse to enable a reliable determination of the three-dimensional structure of the entire Taurus star-forming complex. They do demonstrate, however, that VLBA observations of multiple sources in a given star-forming region have the potential not only to provide a very accurate estimate of its mean distance, but also to reveal its internal structure. The proper motion measurements obtained simultaneously with the parallax allowed us to study the kinematics of the young stars in Taurus. Combining the four observations available so far, we estimate the peculiar velocity of Taurus to be about 10.6 km s -1 almost completely in a direction parallel to the Galactic plane. Using our improved distance measurement, we have refined the determination of the position on the H-R diagram of HP Tau/G2, and of two other members of the HP Tau group (HP Tau itself and HP Tau/G3). Most pre-main-sequence evolutionary models predict significantly discrepant ages (by 5 Myr) for those three stars-expected to be coeval. Only in the models of Palla and Stahler do they fall on a single isochrone (at 3 Myr).

  10. Structural, Mechanical, Anisotropic, and Thermal Properties of AlAs in oC12 and hP6 Phases under Pressure

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2018-05-01

    Full Text Available The structural, mechanical, anisotropic, and thermal properties of oC12-AlAs and hP6-AlAs under pressure have been investigated by employing first-principles calculations based on density functional theory. The elastic constants, bulk modulus, shear modulus, Young’s modulus, B/G ratio, and Poisson’s ratio for oC12-AlAs and hP6-AlAs have been systematically investigated. The results show that oC12-AlAs and hP6-AlAs are mechanically stable within the considered pressure. Through the study of lattice constants (a, b, and c with pressure, we find that the incompressibility of oC12-AlAs and hP6-AlAs is the largest along the c-axis. At 0 GPa, the bulk modulus B of oC12-AlAs, hP6-AlAs, and diamond-AlAs are 76 GPa, 75 GPa, and 74 Gpa, respectively, indicating that oC12-AlAs and hP6-AlAs have a better capability of resistance to volume than diamond-AlAs. The pressure of transition from brittleness to ductility for oC12-AlAs and hP6-AlAs are 1.21 GPa and 2.11 GPa, respectively. The anisotropy of Young’s modulus shows that oC12-AlAs and hP6-AlAs have greater isotropy than diamond-AlAs. To obtain the thermodynamic properties of oC12-AlAs and hP6-AlAs, the sound velocities, Debye temperature, and minimum thermal conductivity at considered pressure were investigated systematically. At ambient pressure, oC12-AlAs (463 K and hP6-AlAs (471 K have a higher Debye temperature than diamond-AlAs (433 K. At T = 300 K, hP6-AlAs (0.822 W/cm·K−1 has the best thermal conductivity of the three phases, and oC12-AlAs (0.809 W/cm·K−1 is much close to diamond-AlAs (0.813 W/cm·K−1.

  11. Factor Structure and Initial Validation of a Multidimensional Measure of Difficulties in the Regulation of Positive Emotions: The DERS-Positive.

    Science.gov (United States)

    Weiss, Nicole H; Gratz, Kim L; Lavender, Jason M

    2015-05-01

    Emotion regulation difficulties are a transdiagnostic construct relevant to numerous clinical difficulties. Although the Difficulties in Emotion Regulation Scale (DERS) is a multidimensional measure of maladaptive ways of responding to emotions, it focuses on difficulties with the regulation of negative emotions and does not assess emotion dysregulation in the form of problematic responding to positive emotions. The aim of this study was to develop and validate a measure of clinically relevant difficulties in the regulation of positive emotions (DERS-Positive). Findings revealed a three-factor structure and supported the internal consistency and construct validity of the total and subscale scores. © The Author(s) 2015.

  12. Heart position variability during voluntary moderate deep inspiration breath-hold radiotherapy for breast cancer determined by repeat CBCT scans.

    Science.gov (United States)

    van Haaren, Paul; Claassen-Janssen, Fiere; van de Sande, Ingrid; Boersma, Liesbeth; van der Sangen, Maurice; Hurkmans, Coen

    2017-08-01

    Voluntary moderate deep inspiration breath hold (vmDIBH) in left-sided breast cancer radiotherapy reduces cardiac dose. The aim of this study was to investigate heart position variability in vmDIBH using CBCT and to compare this variability with differences in heart position between vmDIBH and free breathing (FB). For 50 patients initial heart position with respect to the field edge (HP-FE) was measured on a vmDIBH planning CT scan. Breath-hold was monitored using an in-house developed vertical plastic stick. On pre-treatment CBCT scans, heart position variability with respect to the field edge (Δ HP-FE ) was measured, reflecting heart position variability when using an offline correction protocol. After registering the CBCT scan to the planning CT, heart position variability with respect to the chest wall (Δ HP-CW ) was measured, reflecting heart position variability when using an online correction protocol. As a control group, vmDIBH and FB computed tomography (CT) scans were acquired for 30 patients and registering both scans on the chest wall. For 34 out of 50 patients, the average HP-FE and HP-CW increased over the treatment course in comparison to the planning CT. Averaged over all patients and all treatment fractions, the Δ HP-FE and the Δ HP-CW was 0.8±4.2mm (range -9.4-+10.6mm) and 1.0±4.4mm (range -8.3-+10.4mm) respectively. The average gain in heart to chest wall distance was 11.8±4.6mm when using vmDIBH instead of FB. In conclusion, substantial variability in heart position using vmDIBH was observed during the treatment course. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  13. Positive emotion in distress as a potentially effective emotion regulation strategy for depression: A preliminary investigation.

    Science.gov (United States)

    Yamaguchi, Keiko; Ito, Masaya; Takebayashi, Yoshitake

    2018-03-12

    Emotion regulation utilizing positive emotion during negative emotional states might be one of the effective ways to alleviate depression and anxiety problems among people with emotional disorders. This study examined the psychometric properties and incremental validity of the Positive Emotion In Distress Scale (PEIDS), a newly developed self-report scale, in a sample of university students in Japan. To examine the psychometric properties of the PEIDS, the scale was completed by Japanese university students (396 men and 363 women; mean age of 19.92). Participants additionally answered the Emotion Regulation Questionnaire, Rumination and Reflection Questionnaire - Shorter Version, Affective Style Questionnaire, Positive and Negative Affective Schedule, and Hospital Anxiety and Depression Scale. The survey was conducted at two time points separated by 1 month to assess test-retest reliability and validity of the PEIDS. Exploratory and confirmatory factor analyses confirmed a one-factor structure. Reliability was confirmed by high internal consistency and test-retest stability; the convergent and discriminant validity was confirmed by correlations with related and unrelated variables. The results of hierarchical regression analyses demonstrated that positive emotion in distress might predict depression above and beyond the effect of baseline depression and other common emotion regulation strategies. The PEIDS showed acceptable reliability and validity within young adults and a non-clinical population in Japan. Further research will be needed to examine the effect of positive emotion among clinical populations. Previous research suggests that positive emotions play a key role in recovery from depression and anxiety problems through some forms of psychotherapy. The Positive Emotion In Distress Scale (PEIDS) measures individual differences regarding the extent to which people can experience positive emotions in negative emotional states. Results suggested that the

  14. Determination of the dose equivalent Hp(0.07) in hands of occupationally exposed personnel in the practice of proton emission tomography (PET/CT)

    International Nuclear Information System (INIS)

    Lea, D.; Ruiz, N.; Esteves, L.

    2006-01-01

    In Venezuela recently it was implanted the Positron Emission Tomography technique (PET) with the perspective of implanting it at national level. Even when in our country practices it of nuclear medicine it exists from early of 70, there is not experience in the determination of the occupational doses by exposure to the external radiation in hands. By this reason, a concern exists in the workers of the centers of nuclear medicine where it is practiced the Positron Emission Tomography technique. In absence of the TLD dosimetry to measure dose in hands in our country, measurements of the dose equivalent of the workers of the PET national reference center were made, using a detector of hands type diode. It was determined the dose in hands in terms of dose equivalent Hp(0.07) in two work positions, that is: the corresponding to the transfer of the receiving vial of ( 18 F) FDG to the shield, quality control and uni doses division. The second work position corresponds the person in charge of administering, via intravenous, the ( 18 F) FDG. In this work it realizes the dose equivalent in hands Hp(0.07) measures in each one of the work positions before described by daily production. The informed doses correspond to a total average produced activity of 20.4 GBq (550 mCi). The results of the measurements in terms of dose equivalent in hands Hp(0.07) correspond to 2.1 ± 20% mSv in the work position of division and 0.4 ± 10% mSv in the position of injection of the radioactive material. At short term this foreseen until 4 productions per week, what means an annual dose equivalent Hp(0.07) in hands of 400 mSv approximately, without taking into account abnormal situations as its are spills of the ( 18 F) FDG in the work place. This work is the starting point so that the regulatory authority settles down, in Venezuela, dose restrictions in the PET practices and implant, in the centers of nuclear medicine, an optimization politics of this practice in conformity with the ALARA

  15. Space-time adaptive hp-FEM for problems with traveling sharp fronts

    Czech Academy of Sciences Publication Activity Database

    Šolín, Pavel; Korous, L.

    2013-01-01

    Roč. 95, č. 1 (2013), S709-S722 ISSN 0010-485X Institutional support: RVO:61388998 Keywords : adaptive hp-FEM * transient problems * sharp fronts Subject RIV: BA - General Mathematics Impact factor: 1.055, year: 2013

  16. Spectral/ hp element methods: Recent developments, applications, and perspectives

    Science.gov (United States)

    Xu, Hui; Cantwell, Chris D.; Monteserin, Carlos; Eskilsson, Claes; Engsig-Karup, Allan P.; Sherwin, Spencer J.

    2018-02-01

    The spectral/ hp element method combines the geometric flexibility of the classical h-type finite element technique with the desirable numerical properties of spectral methods, employing high-degree piecewise polynomial basis functions on coarse finite element-type meshes. The spatial approximation is based upon orthogonal polynomials, such as Legendre or Chebychev polynomials, modified to accommodate a C 0 - continuous expansion. Computationally and theoretically, by increasing the polynomial order p, high-precision solutions and fast convergence can be obtained and, in particular, under certain regularity assumptions an exponential reduction in approximation error between numerical and exact solutions can be achieved. This method has now been applied in many simulation studies of both fundamental and practical engineering flows. This paper briefly describes the formulation of the spectral/ hp element method and provides an overview of its application to computational fluid dynamics. In particular, it focuses on the use of the spectral/ hp element method in transitional flows and ocean engineering. Finally, some of the major challenges to be overcome in order to use the spectral/ hp element method in more complex science and engineering applications are discussed.

  17. Painting of fourth and chromosome-wide regulation of the 4th chromosome in Drosophila melanogaster.

    Science.gov (United States)

    Johansson, Anna-Mia; Stenberg, Per; Bernhardsson, Carolina; Larsson, Jan

    2007-05-02

    Drosophila melanogaster exhibits two expression-regulating systems that target whole, specific chromosomes: the dosage compensation system whereby the male-specific lethal complex doubles transcription of genes on the male X-chromosome and the chromosome 4-specific protein Painting of fourth, POF. POF is the first example of an autosome-specific protein and its presence raises the question of the universality of chromosome-specific regulation. Here we show that POF and heterochromatin protein 1 (HP1) are involved in the global regulation of the 4th chromosome. Contrary to previous conclusions, Pof is not essential for survival of diplo-4th karyotype flies. However, Pof is essential for survival of haplo-4th individuals and expression of chromosome 4 genes in diplo-4th individuals is decreased in the absence of Pof. Mapping of POF using chromatin immunoprecipitation suggested that it binds within genes. Furthermore, we show that POF binding is dependent on heterochromatin and that POF and HP1 bind interdependently to the 4th chromosome. We propose a balancing mechanism involving POF and HP1 that provides a feedback system for fine-tuning expression status of genes on the 4th chromosome.

  18. Prolyl isomerase Pin1 is highly expressed in Her2-positive breast cancer and regulates erbB2 protein stability

    Directory of Open Access Journals (Sweden)

    Lu Kun

    2008-12-01

    Full Text Available Abstract Overexpression of HER-2/Neu occurs in about 25–30% of breast cancer patients and is indicative of poor prognosis. While Her2/Neu overexpression is primarily a result of erbB2 amplification, it has recently been recognized that erbB2 levels are also regulated on the protein level. However, factors that regulate Her2/Neu protein stability are less well understood. The prolyl isomerase Pin1 catalyzes the isomerization of specific pSer/Thr-Pro motifs that have been phosphorylated in response to mitogenic signaling. We have previously reported that Pin1-catalyzed post-phosphorylational modification of signal transduction modulates the oncogenic pathways downstream from c-neu. The goal of this study was to examine the expression of prolyl isomerase Pin1 in human Her2+ breast cancer, and to study if Pin1 affects the expression of Her2/Neu itself. Methods Immunohistochemistry for Her2 and Pin1 were performed on two hundred twenty-three human breast cancers, with 59% of the specimen from primary cancers and 41% from metastatic sites. Pin1 inhibition was achieved using siRNA in Her2+ breast cancer cell lines, and its effects were studied using cell viability assays, immunoblotting and immunofluorescence. Results Sixty-four samples (28.7% stained positive for Her2 (IHC 3+, and 54% (122/223 of all breast cancers stained positive for Pin1. Of the Her2-positive cancers 40 (62.5% were also Pin1-positive, based on strong nuclear or nuclear and cytoplasmic staining. Inhibition of Pin1 via RNAi resulted in significant suppression of Her2-positive tumor cell growth in BT474, SKBR3 and AU565 cells. Pin1 inhibition greatly increased the sensitivity of Her2-positive breast cancer cells to the mTOR inhibitor Rapamycin, while it did not increase their sensitivity to Trastuzumab, suggesting that Pin1 might act on Her2 signaling. We found that Pin1 interacted with the protein complex that contains ubiquitinated erbB2 and that Pin1 inhibition accelerated erbB2

  19. HP-HMG versus rFSH in treatments combining fresh and frozen IVF cycles: success rates and economic evaluation.

    Science.gov (United States)

    Wex-Wechowski, Jaro; Abou-Setta, Ahmed M; Kildegaard Nielsen, Sandy; Kennedy, Richard

    2010-08-01

    The economic implications of the choice of gonadotrophin influence decision making but their cost-effectiveness in frozen-embryo transfer cycles has not been adequately studied. An economic evaluation was performed comparing highly purified human menopausal gonadotrophin (HP-HMG) and recombinant FSH (rFSH) using individual patient data (n=986) from two large randomized controlled trials using a long agonist IVF protocol. The simulation model incorporated live birth data and published UK costs of IVF-related medical resources. After treatment for up-to-three cycles (one fresh and up to two subsequent fresh or frozen cycles conditional on availability of cryopreserved embryos), the cumulative live birth rate was 53.7% (95% CI 49.3-58.1%) for HP-HMG and 44.6% (40.2-49.0%) for rFSH (OR 1.44, 95% CI 1.12-1.85; Pcosts per IVF treatment for HP-HMG and rFSH were pound5393 ( pound5341-5449) and pound6269 ( pound6210-6324), respectively (number needed to treat to fund one additional treatment was seven; Pcosts applied, the median cost per IVF baby delivered with HP-HMG was pound11,157 ( pound11,089-11,129) and pound14,227 ( pound14,183-14,222) with rFSH (Pcost saving using HP-HMG remained after varying model parameters in a probabilistic sensitivity analysis. 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  20. The transport kinetics and selectivity of HpUreI, the urea channel from Helicobacter pylori†

    Science.gov (United States)

    Gray, Lawrence R; Gu, Sean X; Quick, Matthias; Khademi, Shahram

    2017-01-01

    Helicobacter pylori’s unique ability to colonize and survive in the acidic environment of the stomach is critically dependent on uptake of urea through the urea channel, HpUreI. Hence, HpUreI may represent a promising target for the development of specific drugs against this human pathogen. To obtain insight into the structure/function relationship of this channel, we have developed conditions for the high-yield expression and purification of stable recombinant HpUreI that allowed its detailed kinetic characterization in solubilized form and reconstituted into liposomes. Detergent-solubilized HpUreI forms homo-trimer, as determined by chemical cross-linking. Urea dissociation kinetics of purified HpUreI were determined by means of the scintillation proximity assay (SPA), whereas urea efflux was measured in HpUreI-containing proteoliposomes using stopped-flow spectrometry to determine the kinetics and selectivity of the urea channel. The kinetic analyses revealed that urea conduction in HpUreI is pH sensitive and saturable with a half-saturation concentration (or K0.5) of ~163 mM. Binding of urea by HpUreI was increased at lower pH; however, the apparent affinity of urea binding (~150 mM) was not significantly pH dependent. The solute selectivity analysis indicated that HpUreI is highly selective for urea and hydroxyurea. Removing either amino group of urea molecules diminishes their permeability through HpUreI. Similar to urea conduction, water diffusion through HpUreI is pH-dependent with low water permeability at neutral pH. PMID:21877689

  1. Self-regulation as a mediator between sibling relationship quality and early adolescents' positive and negative outcomes.

    Science.gov (United States)

    Padilla-Walker, Laura M; Harper, James M; Jensen, Alexander C

    2010-08-01

    The current study examined the role of adolescents' self-regulation as a mediator between sibling relationship quality and adolescent outcomes, after controlling for the quality of the parent-child relationship. Participants were 395 families (282 two parent; 113 single parent) with an adolescent child (M age of child at Time 1 = 11.15, SD = .96, 49% female) who took part in [project name masked for blind review] at both Time 1 and Time 2. Path analysis via structural equation modeling suggested that sibling affection was longitudinally and positively related to self-regulation and prosocial behaviors, and negatively related to externalizing behaviors; while sibling hostility was positively, and having a sister was negatively related to internalizing behaviors (in general, paths were stronger for adolescents from two- vs. single-parent families). There was also evidence that adolescents' self-regulation partially mediated the relation between sibling affection and positive and negative adolescent outcomes. The discussion focuses on the importance of continued research examining the mechanisms through which the sibling relationship influences development during adolescence.

  2. RUNX1 positively regulates the ErbB2/HER2 signaling pathway through modulating SOS1 expression in gastric cancer cells.

    Science.gov (United States)

    Mitsuda, Yoshihide; Morita, Ken; Kashiwazaki, Gengo; Taniguchi, Junichi; Bando, Toshikazu; Obara, Moeka; Hirata, Masahiro; Kataoka, Tatsuki R; Muto, Manabu; Kaneda, Yasufumi; Nakahata, Tatsutoshi; Liu, Pu Paul; Adachi, Souichi; Sugiyama, Hiroshi; Kamikubo, Yasuhiko

    2018-04-23

    The dual function of runt-related transcriptional factor 1 (RUNX1) as an oncogene or oncosuppressor has been extensively studied in various malignancies, yet its role in gastric cancer remains elusive. Up-regulation of the ErbB2/HER2 signaling pathway is frequently-encountered in gastric cancer and contributes to the maintenance of these cancer cells. This signaling cascade is partly mediated by son of sevenless homolog (SOS) family, which function as adaptor proteins in the RTK cascades. Herein we report that RUNX1 regulates the ErbB2/HER2 signaling pathway in gastric cancer cells through transactivating SOS1 expression, rendering itself an ideal target in anti-tumor strategy toward this cancer. Mechanistically, RUNX1 interacts with the RUNX1 binding DNA sequence located in SOS1 promoter and positively regulates it. Knockdown of RUNX1 led to the decreased expression of SOS1 as well as dephosphorylation of ErbB2/HER2, subsequently suppressed the proliferation of gastric cancer cells. We also found that our novel RUNX inhibitor (Chb-M') consistently led to the deactivation of the ErbB2/HER2 signaling pathway and was effective against several gastric cancer cell lines. Taken together, our work identified a novel interaction of RUNX1 and the ErbB2/HER2 signaling pathway in gastric cancer, which can potentially be exploited in the management of this malignancy.

  3. FIST - a suite of X-ray powder crystallography programs for use with a HP-65 calculator

    International Nuclear Information System (INIS)

    Ferguson, I.F.; Turek, M.

    1977-12-01

    Programs for X-ray powder crystallography are defined for use with a Hewlett Packard HP-65 (programmable) pocket calculator. These include the prediction of all Bragg reflections for defined P-, F-, I-cubic, tetragonal, hexagonal and orthorhombic cells; the calculation of the position of a specific Bragg reflection from defined unit cells with all symmetries except triclinic; interconversion of theta, 2theta, sin 2 theta and d, as well as the calculation of the Nelson-Riley function; the computation of crystal densities; the interconversion of rhombohedral and hexagonal unit cells, lsub(c) determinations for graphite, the calculation of a and c for boron carbide; and Miller index transformations between various unit cells. (author)

  4. Identification of small molecules that disrupt signaling between ABL and its positive regulator RIN1.

    Directory of Open Access Journals (Sweden)

    Pamela Y Ting

    Full Text Available Constitutively active BCR-ABL kinase fusions are causative mutations in the pathogenesis of hematopoietic neoplasias including chronic myelogenous leukemia (CML. Although these fusions have been successfully targeted with kinase inhibitors, drug-resistance and relapse continue to limit long-term survival, highlighting the need for continued innovative drug discovery. We developed a time-resolved Förster resonance energy transfer (TR-FRET -based assay to identify compounds that disrupt stimulation of the ABL kinase by blocking its ability to bind the positive regulator RIN1. This assay was used in a high throughput screen (HTS of two small molecule libraries totaling 444,743 compounds. 708 confirmed hits were counter-screened to eliminate off-target inhibitors and reanalyzed to prioritize compounds with IC50 values below 10 μM. The CML cell line K562 was then used to identify five compounds that decrease MAPK1/3 phosphorylation, which we determined to be an indicator of RIN1-dependent ABL signaling. One of these compounds is a thiadiazole, and the other four are structurally related acyl piperidine amides. Notably, these five compounds lower cellular BCR-ABL1 kinase activity by blocking a positive regulatory interaction rather than directly inhibiting ABL catalytic function.

  5. On a Weak Discrete Maximum Principle for hp-FEM

    Czech Academy of Sciences Publication Activity Database

    Šolín, Pavel; Vejchodský, Tomáš

    -, č. 209 (2007), s. 54-65 ISSN 0377-0427 R&D Projects: GA ČR(CZ) GA102/05/0629 Institutional research plan: CEZ:AV0Z20570509; CEZ:AV0Z10190503 Keywords : discrete maximum principle * hp-FEM Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 0.943, year: 2007

  6. A proposal for a test method for assessment of hazard property HP 12 (“Release of an acute toxic gas”) in hazardous waste classification - Experience from 49 waste

    OpenAIRE

    Hennebert , Pierre; Samaali , Ismahen; Molina , Pauline

    2016-01-01

    International audience; A stepwise method for assessment of the HP 12 is proposed and tested with 49 waste samples. The hazard property HP 12 is defined as “Release of an acute toxic gas”: waste which releases acute toxic gases (Acute Tox. 1, 2 or 3) in contact with water or an acid. When a waste contains a substance assigned to one of the following supplemental hazards EUH029, EUH031 and EUH032, it shall be classified as hazardous by HP 12 according to test methods or guidelines (EC, 2014a, ...

  7. hp-FEM electromechanical transduction model of ionic polymer metal composites

    Czech Academy of Sciences Publication Activity Database

    Pugal, D.; Šolín, Pavel; Kim, K.; Aabloo, A.

    2014-01-01

    Roč. 260, April (2014), s. 135-148 ISSN 0377-0427 R&D Projects: GA ČR(CZ) GAP102/11/0498 Institutional support: RVO:61388998 Keywords : hp-FEM * Nernst-Planck * Poisson Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 1.266, year: 2014

  8. Aspirin regulation of c-myc and cyclinD1 proteins to overcome tamoxifen resistance in estrogen receptor-positive breast cancer cells.

    Science.gov (United States)

    Cheng, Ran; Liu, Ya-Jing; Cui, Jun-Wei; Yang, Man; Liu, Xiao-Ling; Li, Peng; Wang, Zhan; Zhu, Li-Zhang; Lu, Si-Yi; Zou, Li; Wu, Xiao-Qin; Li, Yu-Xia; Zhou, You; Fang, Zheng-Yu; Wei, Wei

    2017-05-02

    Tamoxifen is still the most commonly used endocrine therapy drug for estrogen receptor (ER)-positive breast cancer patients and has an excellent outcome, but tamoxifen resistance remains a great impediment to successful treatment. Recent studies have prompted an anti-tumor effect of aspirin. Here, we demonstrated that aspirin not only inhibits the growth of ER-positive breast cancer cell line MCF-7, especially when combined with tamoxifen, but also has a potential function to overcome tamoxifen resistance in MCF-7/TAM. Aspirin combined with tamoxifen can down regulate cyclinD1 and block cell cycle in G0/G1 phase. Besides, tamoxifen alone represses c-myc, progesterone receptor (PR) and cyclinD1 in MCF-7 cell line but not in MCF-7/TAM, while aspirin combined with tamoxifen can inhibit the expression of these proteins in the resistant cell line. When knocking down c-myc in MCF-7/TAM, cells become more sensitive to tamoxifen, cell cycle is blocked as well, indicating that aspirin can regulate c-myc and cyclinD1 proteins to overcome tamoxifen resistance. Our study discovered a novel role of aspirin based on its anti-tumor effect, and put forward some kinds of possible mechanisms of tamoxifen resistance in ER-positive breast cancer cells, providing a new strategy for the treatment of ER-positive breast carcinoma.

  9. A study on directional resistivity logging-while-drilling based on self-adaptive hp-FEM

    Science.gov (United States)

    Liu, Dejun; Li, Hui; Zhang, Yingying; Zhu, Gengxue; Ai, Qinghui

    2014-12-01

    Numerical simulation of resistivity logging-while-drilling (LWD) tool response provides guidance for designing novel logging instruments and interpreting real-time logging data. In this paper, based on self-adaptive hp-finite element method (hp-FEM) algorithm, we analyze LWD tool response against model parameters and briefly illustrate geosteering capabilities of directional resistivity LWD. Numerical simulation results indicate that the change of source spacing is of obvious influence on the investigation depth and detecting precision of resistivity LWD tool; the change of frequency can improve the resolution of low-resistivity formation and high-resistivity formation. The simulation results also indicate that the self-adaptive hp-FEM algorithm has good convergence speed and calculation accuracy to guide the geologic steering drilling and it is suitable to simulate the response of resistivity LWD tools.

  10. Positive Regulation of RNA Metabolic Process” Ontology Group Highly Regulated in Porcine Oocytes Matured In Vitro: A Microarray Approach

    Directory of Open Access Journals (Sweden)

    Piotr Celichowski

    2018-01-01

    Full Text Available The cumulus-oocyte complexes (COCs growth and development during folliculogenesis and oogenesis are accompanied by changes involving synthesis and accumulation of large amount of RNA and proteins. In this study, the transcriptomic profile of genes involved in “oocytes RNA synthesis” in relation to in vitro maturation in pigs was investigated for the first time. The RNA was isolated from oocytes before and after in vitro maturation (IVM. Interactions between differentially expressed genes/proteins belonging to “positive regulation of RNA metabolic process” ontology group were investigated by STRING10 software. Using microarray assays, we found expression of 12258 porcine transcripts. Genes with fold change higher than 2 and with corrected p value lower than 0.05 were considered as differentially expressed. The ontology group “positive regulation of RNA metabolic process” involved differential expression of AR, INHBA, WWTR1, FOS, MEF2C, VEGFA, IKZF2, IHH, RORA, MAP3K1, NFAT5, SMARCA1, EGR1, EGR2, MITF, SMAD4, APP, and NR5A1 transcripts. Since all of the presented genes were downregulated after IVM, we suggested that they might be significantly involved in regulation of RNA synthesis before reaching oocyte MII stage. Higher expression of “RNA metabolic process” related genes before IVM indicated that they might be recognized as important markers and specific “transcriptomic fingerprint” of RNA template accumulation and storage for further porcine embryos growth and development.

  11. miR-25-3p, Positively Regulated by Transcription Factor AP-2α, Regulates the Metabolism of C2C12 Cells by Targeting Akt1

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    2018-03-01

    Full Text Available miR-25, a member of the miR-106b-25 cluster, has been reported as playing an important role in many biological processes by numerous studies, while the role of miR-25 in metabolism and its transcriptional regulation mechanism remain unclear. In this study, gain-of-function and loss-of-function assays demonstrated that miR-25-3p positively regulated the metabolism of C2C12 cells by attenuating phosphoinositide 3-kinase (PI3K gene expression and triglyceride (TG content, and enhancing the content of adenosine triphosphate (ATP and reactive oxygen species (ROS. Furthermore, the results from bioinformatics analysis, dual luciferase assay, site-directed mutagenesis, qRT-PCR, and Western blotting demonstrated that miR-25-3p directly targeted the AKT serine/threonine kinase 1 (Akt1 3′ untranslated region (3′UTR. The core promoter of miR-25-3p was identified, and the transcription factor activator protein-2α (AP-2α significantly increased the expression of mature miR-25-3p by binding to its core promoter in vivo, as indicated by the chromatin immunoprecipitation (ChIP assay, and AP-2α binding also downregulated the expression of Akt1. Taken together, our findings suggest that miR-25-3p, positively regulated by the transcription factor AP-2α, enhances C2C12 cell metabolism by targeting the Akt1 gene.

  12. The law concerning the environmental impact assessment. Vol. 1. Collection of regulations with an introduction to EIA law; Das Recht der Umweltvertraeglichkeitspruefung. Bd. 1. Vorschriftensammlung mit Einfuehrung in das UVP-Recht

    Energy Technology Data Exchange (ETDEWEB)

    Peters, H.J.

    1995-12-31

    The present book contains all regulations relevant to EIA in compact form: The EU EIA Directive; the Federal Law on the EIA; the Procedural Rules of Atomic Energy Law; the Ninth Ordinance on the Federal Emissions Control Law including the pertinent general administrative regulation; the Federal Mining Law; the Federal Building Law; the Federal Regional Planning Law; and the EIA laws of the Laender such as implementing regulations, the Land EIA Laws, and the Land Planning Laws. There is a basic introduction to EIA law preceding this collection of regulations and laws. (orig./HP) [Deutsch] Das Buch bietet alle UVP-Vorschriften in kompakter Form, die UVPRL der EU, das UVPG, die Atomrechtliche Verfahrensverordnung (AtVfV) und die 9. BImSchV einschliesslich der entsprechenden Allgemeinen Verwaltungsvorschrift sowie das BBergG, das BauGB, das ROG bis hin zum UVP-Recht der Laender wie DurchfuehrungsVO, LUVPG und Landesplanungsgesetzen. Vorangestellt ist diesen Vorschriften eine grundlegende Einfuehrung in das Recht des UVP. (orig./HP)

  13. A nonlinear HP-type complementary resistive switch

    Directory of Open Access Journals (Sweden)

    Paul K. Radtke

    2016-05-01

    Full Text Available Resistive Switching (RS is the change in resistance of a dielectric under the influence of an external current or electric field. This change is non-volatile, and the basis of both the memristor and resistive random access memory. In the latter, high integration densities favor the anti-serial combination of two RS-elements to a single cell, termed the complementary resistive switch (CRS. Motivated by the irregular shape of the filament protruding into the device, we suggest a nonlinearity in the resistance-interpolation function, characterized by a single parameter p. Thereby the original HP-memristor is expanded upon. We numerically simulate and analytically solve this model. Further, the nonlinearity allows for its application to the CRS.

  14. A nonlinear HP-type complementary resistive switch

    Science.gov (United States)

    Radtke, Paul K.; Schimansky-Geier, Lutz

    2016-05-01

    Resistive Switching (RS) is the change in resistance of a dielectric under the influence of an external current or electric field. This change is non-volatile, and the basis of both the memristor and resistive random access memory. In the latter, high integration densities favor the anti-serial combination of two RS-elements to a single cell, termed the complementary resistive switch (CRS). Motivated by the irregular shape of the filament protruding into the device, we suggest a nonlinearity in the resistance-interpolation function, characterized by a single parameter p. Thereby the original HP-memristor is expanded upon. We numerically simulate and analytically solve this model. Further, the nonlinearity allows for its application to the CRS.

  15. DMBT1 expression is down-regulated in breast cancer

    DEFF Research Database (Denmark)

    Braidotti, P; Nuciforo, P G; Mollenhauer, J

    2004-01-01

    and hyperplastic mammary cells positive with DMBTh12 were also MCM5-positive. CONCLUSIONS: The redistribution and up-regulation of DMBT1 in normal and hyperplastic tissues flanking malignant tumours and its down-regulation in carcinomas suggests a potential role in breast cancer. Moreover, the concomitant......BACKGROUND: We studied the expression of DMBT1 (deleted in malignant brain tumor 1), a putative tumor suppressor gene, in normal, proliferative, and malignant breast epithelium and its possible relation to cell cycle. METHODS: Sections from 17 benign lesions and 55 carcinomas were immunostained...... expression was down-regulated in the cancerous lesions compared to the normal and/or hyperplastic epithelium adjacent to carcinomas (3/55 positive carcinomas versus 33/42 positive normal/hyperplastic epithelia; p = 0.0001). In 72% of cases RT-PCR confirmed immunohistochemical results. Most of normal...

  16. General requirements to implement the personal dose equivalent Hp(10) in Brazil

    International Nuclear Information System (INIS)

    Lopes, Amanda Gomes; Silva, Francisco Cesar Augusto da

    2017-01-01

    To update the dosimetry quantity with the international community, Brazil is changing the Individual Dose Hx to the Personal Dose Equivalent Hp(10). A bibliographical survey on the technical and administrative requirements of nine countries that use Hp(10) was carried out to obtain the most relevant ones. All of them follow IEC and ISO guidelines for technical requirements, while administrative requirements change from country to country. Based on countries experiences, this paper presents a list of important general requirements to implement Hp(10) and to prepare the Brazilian requirements according to the international scientific community. (author)

  17. General requirements to implement the personal dose equivalent Hp(10) in Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Lopes, Amanda Gomes; Silva, Francisco Cesar Augusto da, E-mail: amandagl@bolsista.ird.gov.br [Instituto de Radioproteção e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2017-07-01

    To update the dosimetry quantity with the international community, Brazil is changing the Individual Dose Hx to the Personal Dose Equivalent Hp(10). A bibliographical survey on the technical and administrative requirements of nine countries that use Hp(10) was carried out to obtain the most relevant ones. All of them follow IEC and ISO guidelines for technical requirements, while administrative requirements change from country to country. Based on countries experiences, this paper presents a list of important general requirements to implement Hp(10) and to prepare the Brazilian requirements according to the international scientific community. (author)

  18. The Haptoglobin-CD163-Heme Oxygenase-1 Pathway for Hemoglobin Scavenging

    Directory of Open Access Journals (Sweden)

    Jens Haugbølle Thomsen

    2013-01-01

    Full Text Available The haptoglobin- (Hp- CD163-heme oxygenase-1 (HO-1 pathway is an efficient captor-receptor-enzyme system to circumvent the hemoglobin (Hb/heme-induced toxicity during physiological and pathological hemolyses. In this pathway, Hb tightly binds to Hp leading to CD163-mediated uptake of the complex in macrophages followed by lysosomal Hp-Hb breakdown and HO-1-catalyzed conversion of heme into the metabolites carbon monoxide (CO, biliverdin, and iron. The plasma concentration of Hp is a limiting factor as evident during accelerated hemolysis, where the Hp depletion may cause serious Hb-induced toxicity and put pressure on backup protecting systems such as the hemopexin-CD91-HO pathway. The Hp-CD163-HO-1 pathway proteins are regulated by the acute phase mediator interleukin-6 (IL-6, but other regulatory factors indicate that this upregulation is a counteracting anti-inflammatory response during inflammation. The heme metabolites including bilirubin converted from biliverdin have overall an anti-inflammatory effect and thus reinforce the anti-inflammatory efficacy of the Hp-CD163-HO-1 pathway. Future studies of animal models of inflammation should further define the importance of the pathway in the anti-inflammatory response.

  19. hp-HGS strategy for inverse 3D DC resistivity logging measurement simulations

    KAUST Repository

    Gajda-Zaǵorska, Ewa; Paszý nski, Maciej; Schaefer, Robert; Pardo, David; Calo, Victor M.

    2012-01-01

    In this paper we present a twin adaptive strategy hp-HGS for solving inverse problems related to 3D DC borehole resistivity measurement simulations. The term “simulation of measurements” is widely used by the geophysical community. A quantity of interest, voltage, is measured at a receiver electrode located in the logging instrument. We use the self-adaptive goal-oriented hp-Finite Element Method (hp-FEM) computer simulations of the process of measurements in deviated wells (when the angle between the borehole and formation layers are < 90 deg). We also employ the hierarchical genetic search (HGS) algorithm to solve the inverse problem. Each individual in the population represents a single configuration of the formation layers. The evaluation of the individual is performed by solving the direct problem by means of the hp-FEM algorithm and by comparison with measured logging curve. We conclude the paper with some discussion on the parallelization of the algorithm.

  20. hp-HGS strategy for inverse 3D DC resistivity logging measurement simulations

    KAUST Repository

    Gajda-Zaǵorska, Ewa

    2012-06-02

    In this paper we present a twin adaptive strategy hp-HGS for solving inverse problems related to 3D DC borehole resistivity measurement simulations. The term “simulation of measurements” is widely used by the geophysical community. A quantity of interest, voltage, is measured at a receiver electrode located in the logging instrument. We use the self-adaptive goal-oriented hp-Finite Element Method (hp-FEM) computer simulations of the process of measurements in deviated wells (when the angle between the borehole and formation layers are < 90 deg). We also employ the hierarchical genetic search (HGS) algorithm to solve the inverse problem. Each individual in the population represents a single configuration of the formation layers. The evaluation of the individual is performed by solving the direct problem by means of the hp-FEM algorithm and by comparison with measured logging curve. We conclude the paper with some discussion on the parallelization of the algorithm.

  1. hpGEM -- A software framework for discontinuous Galerkin finite element methods

    NARCIS (Netherlands)

    Pesch, L.; Bell, A.; Sollie, W.E.H.; Ambati, V.R.; Bokhove, Onno; van der Vegt, Jacobus J.W.

    2006-01-01

    hpGEM, a novel framework for the implementation of discontinuous Galerkin finite element methods, is described. We present structures and methods that are common for many (discontinuous) finite element methods and show how we have implemented the components as an object-oriented framework. This

  2. Disaggregated regulation in network sections: The normative and positive theory; Disaggregierte Regulierung in Netzsektoren: Normative und positive Theorie

    Energy Technology Data Exchange (ETDEWEB)

    Knieps, G. [Inst. fuer Verkehrswissenschaft und Regionalpolitik, Albert-Ludwigs-Univ. Freiburg i.B. (Germany)

    2007-09-15

    The article deals with the interaction of normative and positive theorie of regulation. Those parts of the network which need regulation could be localised and regulated with the help of the normative theory of the monopolistic bottlenecks. Using the positive theory, the basic elements of a mandate for regulation in the sense of the disaggregated economy of regulation are derived.

  3. The Relationship between Oral Hygiene Index and Gastric Helicobacter Pylori Positivity

    Directory of Open Access Journals (Sweden)

    Tolga Önder

    2016-03-01

    Full Text Available Objective: Helicobacter pylori (HP is a bacterial patho­gen that leads to gastroduodenal inflammation, gastric and duodenal ulcer and atrophic gastritis. Colonization of bacteria can be shown by using rapid-urease test during endoscopy. There are conflicting data about the route of transmission and reservoir. It’s thought to be transmitted primarily by oral route. Many studies showed results sup­porting that the presence of bacteria in dental plaques has effects on gastric colonization and eradication. There are data about the potential inhibitory effect of oral flora on HP. We aimed to analyze the association of simplified oral hygiene index -a possible representation of a healthy oral flora- with HP positivity. Methods: Patients undergoing upper gastrointestinal system endoscopy for symptoms of dyspepsia were as­sessed by a dentist for the simplified oral hygiene index (OHI. Patients were classified as good, poor and bad groups based on oral hygiene index scale. Pre-pyloric biopsy materials were assessed using rapid-urease test. Oral hygiene indexes were analyzed retrospectively, groups were compared for HP positivity. Results: 66 patients (30 females, 45.5% were included. Mean age of patients was 34.17±14.7 years. 11 (16.7%, 29 (43.9% and 26 (39.4% patients were classified as in good, poor and bad hygiene index groups, respectively. In patients with good OHI gastric HP positivity was less frequent. Conclusion: Decreased frequency in gastric HP may be observed with maintaining an ideal oral hygiene.

  4. Connection of position sensing circuit of regulating body

    International Nuclear Information System (INIS)

    Janosek, B.

    1988-01-01

    The source of position pulses is connected to the evaluation unit to which is also connected a display which in turn is connected to a numerical selection unit connected via a power output to the action drive unit. A feedback member is connected between the evaluation unit and the numerical selection unit. Changes in the position of the regulating body produces voltage in the position sensor proportional to the actual value of this change. Voltage pulses are led via a measuring amplifier to the evaluation unit. After amplification the pulses are compared with the value on the numerical selection unit connected in the feedback branch to the measuring amplifier which evaluates differential values of pulses shown on the display in form of instantaneous and required values. The required value is selected via the numerical unit. (J.B.). 1 fig

  5. Liposome-encapsulated EF24-HP{beta}CD inclusion complex: a preformulation study and biodistribution in a rat model

    Energy Technology Data Exchange (ETDEWEB)

    Agashe, H; Lagisetty, P; Sahoo, K; Bourne, D [University of Oklahoma Health Sciences Center, Department of Pharmaceutical Sciences (United States); Grady, B [School of Chemical, Biological and Materials Engineering (United States); Awasthi, V [University of Oklahoma Health Sciences Center, Department of Pharmaceutical Sciences (United States)

    2011-06-15

    3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24) is an anti-proliferative diphenyldifluoroketone analog of curcumin with more potent activity. The authors describe a liposome preparation of EF24 using a 'drug-in-CD-in liposome' approach. An aqueous solution of EF24 and hydroxypropyl-{beta}-cyclodextrin (HP{beta}CD) inclusion complex (IC) was used to prepare EF24 liposomes. The liposome size was reduced by a combination of multiple freeze-thaw cycles. Co-encapsulation of glutathione inside the liposomes conferred them with the capability of labeling with imageable radionuclide Tc-99m. Phase solubility analysis of EF24-HP{beta}CD mixture provided k{sub 1:1} value of 9.9 M{sup -1}. The enhanced aqueous solubility of EF24 (from 1.64 to 13.8 mg/mL) due to the presence of HP{beta}CD helped in the liposome preparation. About 19% of the EF24 IC was encapsulated inside the liposomes (320.5 {+-} 2.6 nm) by dehydration-rehydration technique. With extrusion technique, the size of 177 {+-} 6.5 nm was obtained without any effect on encapsulation efficiency. The EF24-liposomes were evaluated for anti-proliferative activity in lung adenocarcinoma H441 and prostate cancer PC-3 cells. The EF24-liposomes demonstrated anti-proliferative activity superior to that of plain EF24 at 10 {mu}M dose. When injected in rats, the Tc-99m-labeled EF24-liposomes cleared from blood with an {alpha}-t{sub 1/2} of 21.4 min and {beta}-t{sub 1/2} of 397 min. Tissue radioactivity counting upon necropsy showed that the majority of clearance was due to the uptake in liver and spleen. The results suggest that using 'drug-in-CD-in liposome' approach is a feasible strategy to formulate an effective parenteral preparation of EF24. In vitro studies show that the liposomal EF24 remains anti-proliferative, while presenting an opportunity to image its biodistribution.

  6. Liposome-encapsulated EF24-HP{beta}CD inclusion complex: a preformulation study and biodistribution in a rat model

    Energy Technology Data Exchange (ETDEWEB)

    Agashe, H.; Lagisetty, P.; Sahoo, K.; Bourne, D. [University of Oklahoma Health Sciences Center, Department of Pharmaceutical Sciences (United States); Grady, B. [School of Chemical, Biological and Materials Engineering (United States); Awasthi, V., E-mail: vawasthi@ouhsc.edu [University of Oklahoma Health Sciences Center, Department of Pharmaceutical Sciences (United States)

    2011-06-15

    3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24) is an anti-proliferative diphenyldifluoroketone analog of curcumin with more potent activity. The authors describe a liposome preparation of EF24 using a 'drug-in-CD-in liposome' approach. An aqueous solution of EF24 and hydroxypropyl-{beta}-cyclodextrin (HP{beta}CD) inclusion complex (IC) was used to prepare EF24 liposomes. The liposome size was reduced by a combination of multiple freeze-thaw cycles. Co-encapsulation of glutathione inside the liposomes conferred them with the capability of labeling with imageable radionuclide Tc-99m. Phase solubility analysis of EF24-HP{beta}CD mixture provided k{sub 1:1} value of 9.9 M{sup -1}. The enhanced aqueous solubility of EF24 (from 1.64 to 13.8 mg/mL) due to the presence of HP{beta}CD helped in the liposome preparation. About 19% of the EF24 IC was encapsulated inside the liposomes (320.5 {+-} 2.6 nm) by dehydration-rehydration technique. With extrusion technique, the size of 177 {+-} 6.5 nm was obtained without any effect on encapsulation efficiency. The EF24-liposomes were evaluated for anti-proliferative activity in lung adenocarcinoma H441 and prostate cancer PC-3 cells. The EF24-liposomes demonstrated anti-proliferative activity superior to that of plain EF24 at 10 {mu}M dose. When injected in rats, the Tc-99m-labeled EF24-liposomes cleared from blood with an {alpha}-t{sub 1/2} of 21.4 min and {beta}-t{sub 1/2} of 397 min. Tissue radioactivity counting upon necropsy showed that the majority of clearance was due to the uptake in liver and spleen. The results suggest that using 'drug-in-CD-in liposome' approach is a feasible strategy to formulate an effective parenteral preparation of EF24. In vitro studies show that the liposomal EF24 remains anti-proliferative, while presenting an opportunity to image its biodistribution.

  7. Mutation of charged residues to neutral ones accelerates urea denaturation of HP-35.

    Science.gov (United States)

    Wei, Haiyan; Yang, Lijiang; Gao, Yi Qin

    2010-09-16

    Following the studies of urea denaturation of β-hairpins using molecular dynamics, in this paper, molecular dynamics simulations of two peptides, a 35 residue three helix bundle villin headpiece protein HP-35 and its doubly norleucine-substituent mutant (Lys24Nle/Lys29Nle) HP-35 NleNle, were undertaken in urea solutions to understand the molecular mechanism of urea denaturation of α-helices. The mutant HP-35 NleNle was found to denature more easily than the wild type. During the expansion of the small hydrophobic core, water penetration occurs first, followed by that of urea molecules. It was also found that the initial hydration of the peptide backbone is achieved through water hydrogen bonding with the backbone CO groups during the denaturation of both polypeptides. The mutation of the two charged lysine residues to apolar norleucine enhances the accumulation of urea near the hydrophobic core and facilitates the denaturation process. Urea also interacts directly with the peptide backbone as well as side chains, thereby stabilizing nonnative conformations. The mechanism revealed here is consistent with the previous study on secondary structure of β-hairpin polypeptide, GB1, PEPTIDE 1, and TRPZIP4, suggesting that there is a general mechanism in the denaturation of protein backbone hydrogen bonds by urea.

  8. Synthesis gas generation by high pressure partial oxidation (HP POX {sup registered}); Synthesegaserzeugung durch Hochdruck-Partialoxidation (HP POX {sup registered})

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, B.; Seifert, P.; Zeissler, R. [Technische Univ. Bergakademie Freiberg (Germany). Inst. fuer Energieverfahrenstechnik und Chemieingenieurwesen; Walter, St. [Lurgi AG, Frankfurt/Main (Germany)

    2005-05-01

    The high pressure synthesis gas process HP POX (High Pressure Partial Oxidation) is a thermal conversion process, which converts e.g. natural gas or heavy residue oil with oxygen to fuel or synthesis gas. Innovative burner technologies allow autothermal catalytic or non-catalytic reforming of gaseous feedstock and gasification of liquid feed streams. Hydrogen and carbon monoxide rich synthesis gases with low methane content (particularly suitable as feed gas for methanol synthesis) can be generated. The technology represents a new generation of entrained flow gasification characterized by the new developed equipment and a design pressure of 100 bar. According to the feeds, the HP POX gasification process is the link between the downstream synthesis chemistry (use of gaseous and liquid feeds) and the power plant process (liquid or solid fuels as suspension or slurry). The HP POX development is carried out together with the Lurgi AG at the Institute for Energy Process Engineering and Chemical Engineering (IEC). The 5 MW HP POX test plant built in Freiberg by Lurgi is core of the joint research project, which is supported by the German Federal Ministry of Economics and Labour (BMWA), the Saxon Ministry of Science and the Fine Arts (SMWK), and the mg technologies ag (parent company of Lurgi). The conducted sets of experiments indicate that the unit can be operated in a safe, smooth and stable manner. During this periods of operation, which included nine test campaigns for autothermal reforming (ATR), the maximum pressure for ATR amounted to 70 bar which exceeds the current benchmark in industry for 30 bar. Main objective of R and D work is the development of modelling tools for extreme gasification conditions and different gasification principles of up to 100 bar. These tools are supposed to improve the understanding of the entire gasification process. Their development requires a systematic investigation of the reaction mechanisms and the interactions with the process

  9. Scoring the home falls and accidents screening tool for health professionals (HOME FAST-HP): Evidence from one epidemiological study.

    Science.gov (United States)

    Mackenzie, Lynette; Byles, Julie

    2018-03-30

    Falls in older people are a major public health concern. To target falls prevention interventions, screening tools need to be able to identify older people at greater risk of falling. This study aimed to investigate the screening capacity of the Home Falls and Accidents Screening Tool for health professionals (HOME FAST-HP), and to identify the best cut-off score to identify older people at higher risk of falls using the HOME FAST-HP. The study used cross-sectional data from a random sample of 650 women from the 1921 to 1926 cohort of the Australian Longitudinal Study of Women's Health (ALSWH). Selected women were sent a postal survey including the HOME FAST-HP, falls history, and other health factors. Scores on the home fast were calculated and the cut-point for optimal sensitivity and specificity of the HOME FAST-HP in relation to falls was assessed using a Receiver Operating Characteristic curve. A total of 567 older women participated (response rate 87%). The mean age of participants was 77.5 yrs (95% CI 77.31-77.70). A total of 153 participants (27%) reported a fall in the previous six months. The mean number of hazards using the HOME FAST-HP was 9.74 (95% CI 9.48-10.01), range 2-22. Non-fallers had a mean of 9.6 hazards (95% CI 9.32-9.91) and fallers had a mean of 10.63 hazards (95% CI 10.08-11.19) which was a significant difference (t = 3.41, P = 0.001). The area under the receiver operator curve (AUC) was 0.58 (95% CI 0.53-0.64). A HOME FAST-HP cut-off score of 9 was associated with the optimal sensitivity for falls (73.9%), with specificity (37.9%), and positive predictive value was 30.6% and negative predictive value was 79.7%. The HOME FAST-HP can be used as a screening tool to identify fallers with a cut-off score of nine indicating a higher risk of falling. © 2018 Occupational Therapy Australia.

  10. HP fotovõistluse finalistid veebis / Henrik Roonemaa

    Index Scriptorium Estoniae

    Roonemaa, Henrik

    2002-01-01

    Hewlett-Packardi koduleheküljel on üleval rahvusvahelise digitaalfotograafia konkursi HP Invision Digital Photography Awards 2002 finalistide tööd, nende hulgas Katrin Arraku foto "Minu kala Vallo"

  11. The law concerning the environmental impact assessment. Vol. 1. Collection of regulations with an introduction to EIA law

    International Nuclear Information System (INIS)

    Peters, H.J.

    1995-01-01

    The present book contains all regulations relevant to EIA in compact form: The EU EIA Directive; the Federal Law on the EIA; the Procedural Rules of Atomic Energy Law; the Ninth Ordinance on the Federal Emissions Control Law including the pertinent general administrative regulation; the Federal Mining Law; the Federal Building Law; the Federal Regional Planning Law; and the EIA laws of the Laender such as implementing regulations, the Land EIA Laws, and the Land Planning Laws. There is a basic introduction to EIA law preceding this collection of regulations and laws. (orig./HP) [de

  12. Effect of Mutations on HP Lattice Proteins

    Science.gov (United States)

    Shi, Guangjie; Vogel, Thomas; Landau, David; Li, Ying; Wüst, Thomas

    2013-03-01

    Using Wang-Landau sampling with approriate trial moves[2], we investigate the effect of different types of mutations on lattice proteins in the HP model. While exact studies have been carried out for short HP proteins[3], the systems we investigate are of much larger size and hence not accessible for exact enumerations. Based on the estimated density of states, we systematically analyse the changes in structure and degeneracy of ground states of particular proteins and measure thermodynamic quantities like the stability of ground states and the specific heat, for example. Both, neutral mutations, which do not change the structure and stability of ground states, as well as critical mutations, which do change the thermodynamic behavior qualitatively, have been observed. Research supported by NSF

  13. A Wheat R2R3-type MYB Transcription Factor TaODORANT1 Positively Regulates Drought and Salt Stress Responses in Transgenic Tobacco Plants

    Directory of Open Access Journals (Sweden)

    Qiuhui Wei

    2017-08-01

    Full Text Available MYB transcription factors play important roles in plant responses to biotic and abiotic stress. In this study, TaODORANT1, a R2R3-MYB gene, was cloned from wheat (Triticum aestivum L.. TaODORANT1 was localized in the nucleus and functioned as a transcriptional activator. TaODORANT1 was up-regulated in wheat under PEG6000, NaCl, ABA, and H2O2 treatments. TaODORANT1-overexpressing transgenic tobacco plants exhibited higher relative water content and lower water loss rate under drought stress, as well as lower Na+ accumulation in leaves under salt stress. The transgenic plants showed higher CAT activity but lower ion leakage, H2O2 and malondialdehyde contents under drought and salt stresses. Besides, the transgenic plants also exhibited higher SOD activity under drought stress. Our results also revealed that TaODORANT1 overexpression up-regulated the expression of several ROS- and stress-related genes in response to both drought and salt stresses, thus enhancing transgenic tobacco plants tolerance. Our studies demonstrate that TaODORANT1 positively regulates plant tolerance to drought and salt stresses.

  14. A proposal for a test method for assessment of hazard property HP 12 ("Release of an acute toxic gas") in hazardous waste classification - Experience from 49 waste.

    Science.gov (United States)

    Hennebert, Pierre; Samaali, Ismahen; Molina, Pauline

    2016-12-01

    A stepwise method for assessment of the HP 12 is proposed and tested with 49 waste samples. The hazard property HP 12 is defined as "Release of an acute toxic gas": waste which releases acute toxic gases (Acute Tox. 1, 2 or 3) in contact with water or an acid. When a waste contains a substance assigned to one of the following supplemental hazards EUH029, EUH031 and EUH032, it shall be classified as hazardous by HP 12 according to test methods or guidelines (EC, 2014a, 2014b). When the substances with the cited hazard statement codes react with water or an acid, they can release HCl, Cl 2 , HF, HCN, PH 3 , H 2 S, SO 2 (and two other gases very unlikely to be emitted, hydrazoic acid HN 3 and selenium oxide SeO 2 - a solid with low vapor pressure). Hence, a method is proposed:For a set of 49 waste, water addition did not produce gas. Nearly all the solid waste produced a gas in contact with hydrochloric acid in 5 min in an automated calcimeter with a volume >0.1L of gas per kg of waste. Since a plateau of pressure is reached only for half of the samples in 5 min, 6 h trial with calorimetric bombs or glass flasks were done and confirmed the results. Identification of the gases by portable probes showed that most of the tested samples emit mainly CO 2 . Toxic gases are emitted by four waste: metallic dust from the aluminum industry (CO), two air pollution control residue of industrial waste incinerator (H 2 S) and a halogenated solvent (organic volatile(s) compound(s)). HF has not been measured in these trials started before the present definition of HP 12. According to the definition of HP 12, only the H 2 S emission of substances with hazard statement EUH031 is accounted for. In view of the calcium content of the two air pollution control residue, the presence of calcium sulphide (EUH031) can be assumed. These two waste are therefore classified potentially hazardous for HP 12, from a total of 49 waste. They are also classified as hazardous for other properties (HP 7

  15. Overexpression of GbWRKY1 positively regulates the Pi starvation response by alteration of auxin sensitivity in Arabidopsis.

    Science.gov (United States)

    Xu, Li; Jin, Li; Long, Lu; Liu, Linlin; He, Xin; Gao, Wei; Zhu, Longfu; Zhang, Xianlong

    2012-12-01

    Overexpression of a cotton defense-related gene GbWRKY1 in Arabidopsis resulted in modification of the root system by enhanced auxin sensitivity to positively regulate the Pi starvation response. GbWRKY1 was a cloned WRKY transcription factor from Gossypium barbadense, which was firstly identified as a defense-related gene and showed moderate similarity with AtWRKY75 from Arabidopsis thaliana. Overexpression of GbWRKY1 in Arabidopsis resulted in attenuated Pi starvation stress symptoms, including reduced accumulation of anthocyanin and impaired density of lateral roots (LR) in low Pi stress. The study also indicated that overexpression of GbWRKY1 caused plants constitutively exhibited Pi starvation response including increased development of LR, relatively high level of total P and Pi, high expression level of some high-affinity Pi transporters and phosphatases as well as enhanced accumulation of acid phosphatases activity during Pi-sufficient. It was speculated that GbWRKY1 may act as a positive regulator in the Pi starvation response as well as AtWRKY75. GbWRKY1 probably involves in the modulation of Pi homeostasis and participates in the Pi allocation and remobilization but do not accumulate more Pi in Pi-deficient condition, which was different from the fact that AtWRKY75 influenced the Pi status of the plant during Pi deprivation by increasing root surface area and accumulation of more Pi. Otherwise, further study suggested that the overexpression plants were more sensitive to auxin than wild-type and GbWRKY1 may partly influence the LPR1-dependent (low phosphate response 1) Pi starvation signaling pathway and was putatively independent of SUMO E3 ligase SIZ1 and PHR1 (phosphate starvation response 1) in response to Pi starvation.

  16. Influence of niobium addition on the high temperature mechanical properties of a centrifugally cast HP alloy

    International Nuclear Information System (INIS)

    Andrade, A.R.; Bolfarini, C.; Ferreira, L.A.M.; Vilar, A.A.A.; Souza Filho, C.D.; Bonazzi, L.H.C.

    2015-01-01

    The influence of niobium addition on the mechanical properties at high temperature of HP alloy has been investigated. Two HP alloys were centrifugally cast with a similar chemical composition differing only in the niobium content. Low strain rate high temperature tensile tests and creep-rupture tests were performed in the range of 900–1100 °C, and the results compared between the alloys. According to the results, the high temperature mechanical behavior of both alloys is controlled by several factors like solid solution, network of eutectic carbides, intradendritic precipitation and dendrite spacing. A significant increase in the mechanical properties for the HP alloy with niobium addition was found within the temperature range of 900–1050 °C. Beyond this temperature the mechanical behavior of both alloys is basically the same

  17. The CompHP Core Competencies Framework for Health Promotion in Europe

    Science.gov (United States)

    Barry, Margaret M.; Battel-Kirk, Barbara; Dempsey, Colette

    2012-01-01

    Background: The CompHP Project on Developing Competencies and Professional Standards for Health Promotion in Europe was developed in response to the need for new and changing health promotion competencies to address health challenges. This article presents the process of developing the CompHP Core Competencies Framework for Health Promotion across…

  18. A new crystal lattice structure of Helicobacter pylori neutrophil-activating protein (HP-NAP)

    International Nuclear Information System (INIS)

    Tsuruta, Osamu; Yokoyama, Hideshi; Fujii, Satoshi

    2012-01-01

    A new crystal lattice structure of H. pylori neutrophil-activating protein has been determined. Iron loading causes a series of conformational changes at the ferroxidase centre. A new crystal lattice structure of Helicobacter pylori neutrophil-activating protein (HP-NAP) has been determined in two forms: the native state (Apo) at 2.20 Å resolution and an iron-loaded form (Fe-load) at 2.50 Å resolution. The highly solvated packing of the dodecameric shell is suitable for crystallographic study of the metal ion-uptake pathway. Like other bacterioferritins, HP-NAP forms a spherical dodecamer with 23 symmetry including two kinds of channels. Iron loading causes a series of conformational changes of amino-acid residues (Trp26, Asp52 and Glu56) at the ferroxidase centre

  19. Sphingosine-1-Phosphate Is a Novel Regulator of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR Activity.

    Directory of Open Access Journals (Sweden)

    Firhan A Malik

    Full Text Available The cystic fibrosis transmembrane conductance regulator (CFTR attenuates sphingosine-1-phosphate (S1P signaling in resistance arteries and has emerged as a prominent regulator of myogenic vasoconstriction. This investigation demonstrates that S1P inhibits CFTR activity via adenosine monophosphate-activated kinase (AMPK, establishing a potential feedback link. In Baby Hamster Kidney (BHK cells expressing wild-type human CFTR, S1P (1μmol/L attenuates forskolin-stimulated, CFTR-dependent iodide efflux. S1P's inhibitory effect is rapid (within 30 seconds, transient and correlates with CFTR serine residue 737 (S737 phosphorylation. Both S1P receptor antagonism (4μmol/L VPC 23019 and AMPK inhibition (80μmol/L Compound C or AMPK siRNA attenuate S1P-stimluated (i AMPK phosphorylation, (ii CFTR S737 phosphorylation and (iii CFTR activity inhibition. In BHK cells expressing the ΔF508 CFTR mutant (CFTRΔF508, the most common mutation causing cystic fibrosis, both S1P receptor antagonism and AMPK inhibition enhance CFTR activity, without instigating discernable correction. In summary, we demonstrate that S1P/AMPK signaling transiently attenuates CFTR activity. Since our previous work positions CFTR as a negative S1P signaling regulator, this signaling link may positively reinforce S1P signals. This discovery has clinical ramifications for the treatment of disease states associated with enhanced S1P signaling and/or deficient CFTR activity (e.g. cystic fibrosis, heart failure. S1P receptor/AMPK inhibition could synergistically enhance the efficacy of therapeutic strategies aiming to correct aberrant CFTR trafficking.

  20. Spectral/hp least-squares finite element formulation for the Navier-Stokes equations

    International Nuclear Information System (INIS)

    Pontaza, J.P.; Reddy, J.N.

    2003-01-01

    We consider the application of least-squares finite element models combined with spectral/hp methods for the numerical solution of viscous flow problems. The paper presents the formulation, validation, and application of a spectral/hp algorithm to the numerical solution of the Navier-Stokes equations governing two- and three-dimensional stationary incompressible and low-speed compressible flows. The Navier-Stokes equations are expressed as an equivalent set of first-order equations by introducing vorticity or velocity gradients as additional independent variables and the least-squares method is used to develop the finite element model. High-order element expansions are used to construct the discrete model. The discrete model thus obtained is linearized by Newton's method, resulting in a linear system of equations with a symmetric positive definite coefficient matrix that is solved in a fully coupled manner by a preconditioned conjugate gradient method. Spectral convergence of the L 2 least-squares functional and L 2 error norms is verified using smooth solutions to the two-dimensional stationary Poisson and incompressible Navier-Stokes equations. Numerical results for flow over a backward-facing step, steady flow past a circular cylinder, three-dimensional lid-driven cavity flow, and compressible buoyant flow inside a square enclosure are presented to demonstrate the predictive capability and robustness of the proposed formulation

  1. Positive Gene Regulation by a Natural Protective miRNA Enables Arbuscular Mycorrhizal Symbiosis.

    Science.gov (United States)

    Couzigou, Jean-Malo; Lauressergues, Dominique; André, Olivier; Gutjahr, Caroline; Guillotin, Bruno; Bécard, Guillaume; Combier, Jean-Philippe

    2017-01-11

    Arbuscular mycorrhizal (AM) symbiosis associates most plants with fungi of the phylum Glomeromycota. The fungus penetrates into roots and forms within cortical cell branched structures called arbuscules for nutrient exchange. We discovered that miR171b has a mismatched cleavage site and is unable to downregulate the miR171 family target gene, LOM1 (LOST MERISTEMS 1). This mismatched cleavage site is conserved among plants that establish AM symbiosis, but not in non-mycotrophic plants. Unlike other members of the miR171 family, miR171b stimulates AM symbiosis and is expressed specifically in root cells that contain arbuscules. MiR171b protects LOM1 from negative regulation by other miR171 family members. These findings uncover a unique mechanism of positive post-transcriptional regulation of gene expression by miRNAs and demonstrate its relevance for the establishment of AM symbiosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Switching the JLab Accelerator Operations Environment from an HP-UX Unix-based to a PC/Linux-based environment

    International Nuclear Information System (INIS)

    Mcguckin, Theodore

    2008-01-01

    The Jefferson Lab Accelerator Controls Environment (ACE) was predominantly based on the HP-UX Unix platform from 1987 through the summer of 2004. During this period the Accelerator Machine Control Center (MCC) underwent a major renovation which included introducing Redhat Enterprise Linux machines, first as specialized process servers and then gradually as general login servers. As computer programs and scripts required to run the accelerator were modified, and inherent problems with the HP-UX platform compounded, more development tools became available for use with Linux and the MCC began to be converted over. In May 2008 the last HP-UX Unix login machine was removed from the MCC, leaving only a few Unix-based remote-login servers still available. This presentation will explore the process of converting an operational Control Room environment from the HP-UX to Linux platform as well as the many hurdles that had to be overcome throughout the transition period

  3. On optimal node and polynomial degree distribution in one-dimensional hp -FEM

    Czech Academy of Sciences Publication Activity Database

    Chleboun, J.; Šolín, Pavel

    2013-01-01

    Roč. 95, č. 1 (2013), s. 75-88 ISSN 1436-5057 R&D Projects: GA ČR GAP105/10/1682 Institutional support: RVO:61388998 Keywords : hp * boundary value problem * optimal mesh Subject RIV: JM - Building Engineering

  4. The Older Adult Positivity Effect in Evaluations of Trustworthiness: Emotion Regulation or Cognitive Capacity?

    Science.gov (United States)

    Zebrowitz, Leslie A; Boshyan, Jasmine; Ward, Noreen; Gutchess, Angela; Hadjikhani, Nouchine

    2017-01-01

    An older adult positivity effect, i.e., the tendency for older adults to favor positive over negative stimulus information more than do younger adults, has been previously shown in attention, memory, and evaluations. This effect has been attributed to greater emotion regulation in older adults. In the case of attention and memory, this explanation has been supported by some evidence that the older adult positivity effect is most pronounced for negative stimuli, which would motivate emotion regulation, and that it is reduced by cognitive load, which would impede emotion regulation. We investigated whether greater older adult positivity in the case of evaluative responses to faces is also enhanced for negative stimuli and attenuated by cognitive load, as an emotion regulation explanation would predict. In two studies, younger and older adults rated trustworthiness of faces that varied in valence both under low and high cognitive load, with the latter manipulated by a distracting backwards counting task. In Study 1, face valence was manipulated by attractiveness (low /disfigured faces, medium, high/fashion models' faces). In Study 2, face valence was manipulated by trustworthiness (low, medium, high). Both studies revealed a significant older adult positivity effect. However, contrary to an emotion regulation account, this effect was not stronger for more negative faces, and cognitive load increased rather than decreased the rated trustworthiness of negatively valenced faces. Although inconsistent with emotion regulation, the latter effect is consistent with theory and research arguing that more cognitive resources are required to process negative stimuli, because they are more cognitively elaborated than positive ones. The finding that increased age and increased cognitive load both enhanced the positivity of trustworthy ratings suggests that the older adult positivity effect in evaluative ratings of faces may reflect age-related declines in cognitive capacity rather

  5. Clerget 100 hp heavy-oil engine

    Science.gov (United States)

    Leglise, Pierre

    1931-01-01

    A complete technical description of the Clerget heavy-oil engine is presented along with the general characteristics. The general characteristics are: 9 cylinders, bore 120 mm, stroke 130 mm, four-stroke cycle engine, rated power limited to 100 hp at 1800 rpm; weight 228 kg; propeller with direct drive and air cooling. Moving parts, engine block, and lubrication are all presented.

  6. Goal-Oriented Self-Adaptive hp Finite Element Simulation of 3D DC Borehole Resistivity Simulations

    KAUST Repository

    Calo, Victor M.

    2011-05-14

    In this paper we present a goal-oriented self-adaptive hp Finite Element Method (hp-FEM) with shared data structures and a parallel multi-frontal direct solver. The algorithm automatically generates (without any user interaction) a sequence of meshes delivering exponential convergence of a prescribed quantity of interest with respect to the number of degrees of freedom. The sequence of meshes is generated from a given initial mesh, by performing h (breaking elements into smaller elements), p (adjusting polynomial orders of approximation) or hp (both) refinements on the finite elements. The new parallel implementation utilizes a computational mesh shared between multiple processors. All computational algorithms, including automatic hp goal-oriented adaptivity and the solver work fully in parallel. We describe the parallel self-adaptive hp-FEM algorithm with shared computational domain, as well as its efficiency measurements. We apply the methodology described to the three-dimensional simulation of the borehole resistivity measurement of direct current through casing in the presence of invasion.

  7. A phantom for assessing the personal dose equivalent, HP(10)

    International Nuclear Information System (INIS)

    Santoro, C.; Filho, J.A

    2013-01-01

    Characteristics of a phantom designed to evaluate the personal dose equivalent, H P (10), and appropriate for photographic dosimetry are presented. It is called HP(10) phantom due to cavities constructed to insert dosimetric films at a depth of 10 mm. The H P (10) phantom is irradiated with ionizing radiation energy, E, from 45 to 1250 keV, with doses ranging from 0.2 to 50 mSv. It is positioned in the direction α = 0 °, and the radiation field focusing perpendicular to its front surface. So, are established calibration curves of dosimeters in the position conventionally true and quantities H P (10). It made a comparison between the responses obtained with the H P (10) phantom and responses obtained when using the calibration procedure recommended by ISO dosimeters. The ISO recommends getting the air kerma, Ka, for photons at test point of the radiation field by an ionization chamber. And through conversion coefficients, h pK (10; E, α), becomes the air kerma for H P (10). The ISO 4037-3 recommendation has been studied by researchers to ensure that the low energy spectral differences occur in radiation fields which are generated by various X-ray equipment, and induce changes in the percentages of conversion coefficients on the order of 10% to 90% . On the basis of the recommendations ISO, this article develops phantom able to assess the dose to the influence of scattering and absorption of radiation, its implications with respect to dosimetry, providing improvement in the assessment of doses. (author)

  8. Clinical efficacy and cost-effectiveness of HP-human FSH (Fostimon®) versus rFSH (Gonal-F®) in IVF-ICSI cycles: a meta-analysis.

    Science.gov (United States)

    Gerli, Sandro; Bini, Vittorio; Favilli, Alessandro; Di Renzo, Gian Carlo

    2013-06-01

    Clinical efficacy of human-derived follicle-stimulating hormone (FSH) versus recombinant FSH (rFSH) in IVF-ICSI cycles has long been compared, but no clear evidence of the superiority of a preparation over the other has been found. Human gonadotropins have been often grouped together, but a different glycosylation may be present in each preparation, therefore influencing the specific bioactivity. To exclude confounding factors, a meta-analysis and a cost-effectiveness analysis were designed to compare effectiveness and cost-effectiveness of a specific highly purified human FSH (HP-hFSH) (Fostimon®) versus rFSH (Gonal-F®) in IVF/ICSI cycles. Research methodology filters were applied in MEDLINE, Current Contents and Web of Science from 1980 to February 2012. Eight randomized trials met selection criteria. The meta-analysis showed no significant differences between rFSH and HP-hFSH treatment in live-birth rate (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.63-1.11), clinical pregnancy rate (OR 0.85, 95% CI 0.68-1.07), number of oocytes retrieved, number of mature oocytes and days of stimulation. The cost-effectiveness ratio was € 7174 in the rFSH group and € 2056 in the HP-hFSH group. HP-hFSH is as effective as rFSH in ovarian stimulation for IVF-ICSI cycles, but the human preparation is more cost-effective.

  9. Experimental investigation of a PCM-HP heat sink on its thermal performance and anti-thermal-shock capacity for high-power LEDs

    International Nuclear Information System (INIS)

    Wu, Yuxuan; Tang, Yong; Li, Zongtao; Ding, Xinrui; Yuan, Wei; Zhao, Xuezhi; Yu, Binhai

    2016-01-01

    Highlights: • A phase-change material (PCM) base heat pipe heat sink (PCM-HP heat sink) is designed. • The PCM-HP heat sink can significantly lower the LED heating rate and temperature. • The PCM-HP heat sink achieves a best anti-thermal-shock capacity in LED cyclic working modes. - Abstract: High-power LEDs demonstrate a number of benefits compared with conventional incandescent lamps and fluorescent lamps, including a longer lifetime, higher brightness and lower power consumption. However, owing to their severe high heat flux, it is difficult to develop effective thermal management of high-power LEDs, especially under cyclic working modes, which cause serious periodic thermal stress and limit further development. Focusing on the above problem, this paper designed a phase-change material (PCM) base heat pipe heat sink (PCM-HP heat sink) that consists of a PCM base, adapter plate, heat pipe and finned radiator. Different parameters, such as three types of interior materials to fill the heat sink, three LED power inputs and eight LED cyclic working modes, were separately studied to investigate the thermal performance and anti-thermal-shock capacity of the PCM-HP heat sink. The results show that the PCM-HP heat sink possesses remarkable thermal performance owing to the reduction of the LED heating rate and peak temperature. More importantly, an excellent anti-thermal-shock capacity of the PCM-HP heat sink is also demonstrated when applied in LED cyclic working modes, and this capacity demonstrates the best range.

  10. Functional and evolutionary analyses of Helicobacter pylori HP0231 (DsbK protein with strong oxidative and chaperone activity characterized by a highly diverged dimerization domain

    Directory of Open Access Journals (Sweden)

    Katarzyna Marta Bocian-Ostrzycka

    2015-10-01

    Full Text Available Helicobacter pylori does not encode the classical DsbA/DsbB oxidoreductases that are crucial for oxidative folding of extracytoplasmic proteins. Instead, this microorganism encodes an untypical two proteins playing a role in disulfide bond formation – periplasmic HP0231, which structure resembles that of EcDsbC/DsbG, and its redox partner, a membrane protein HpDsbI (HP0595 with a -propeller structure. The aim of presented work was to assess relations between HP0231 structure and function.We showed that HP0231 is most closely related evolutionarily to the catalytic domain of DsbG, even though it possesses a catalytic motif typical for canonical DsbA proteins. Similarly, the highly diverged N-terminal dimerization domain is homologous to the dimerization domain of DsbG. To better understand the functioning of this atypical oxidoreductase, we examined its activity using in vivo and in vitro experiments. We found that HP0231 exhibits oxidizing and chaperone activities but no isomerizing activity, even though H. pylori does not contain a classical DsbC. We also show that HP0231 is not involved in the introduction of disulfide bonds into HcpC (Helicobacter cysteine-rich protein C, a protein involved in the modulation of the H. pylori interaction with its host. Additionally, we also constructed a truncated version of HP0231 lacking the dimerization domain, denoted HP0231m, and showed that it acts in E. coli cells in a DsbB-dependent manner. In contrast, HP0231m and classical monomeric EcDsbA (Escherichia coli DsbA protein were both unable to complement the lack of HP0231 in H. pylori cells, though they exist in oxidized forms. HP0231m is inactive in the insulin reduction assay and possesses high chaperone activity, in contrast to EcDsbA. In conclusion, HP0231 combines oxidative functions characteristic of DsbA proteins and chaperone activity characteristic of DsbC/DsbG, and it lacks isomerization activity.

  11. A Lexical Framework for Semantic Annotation of Positive and Negative Regulation Relations in Biomedical Pathways

    DEFF Research Database (Denmark)

    Zambach, Sine; Lassen, Tine

    presented here, we analyze 6 frequently used verbs denoting the regulation relations regulates, positively regulates and negatively regulates through corpus analysis, and propose a formal representation of the acquired knowledge as domain speci¯c semantic frames. The acquired knowledge patterns can thus...

  12. The HP0256 gene product is involved in motility and cell envelope architecture of Helicobacter pylori

    LENUS (Irish Health Repository)

    Douillard, Francois P

    2010-04-08

    Abstract Background Helicobacter pylori is the causative agent for gastritis, and peptic and duodenal ulcers. The bacterium displays 5-6 polar sheathed flagella that are essential for colonisation and persistence in the gastric mucosa. The biochemistry and genetics of flagellar biogenesis in H. pylori has not been fully elucidated. Bioinformatics analysis suggested that the gene HP0256, annotated as hypothetical, was a FliJ homologue. In Salmonella, FliJ is a chaperone escort protein for FlgN and FliT, two proteins that themselves display chaperone activity for components of the hook, the rod and the filament. Results Ablation of the HP0256 gene in H. pylori significantly reduced motility. However, flagellin and hook protein synthesis was not affected in the HP0256 mutant. Transmission electron transmission microscopy revealed that the HP0256 mutant cells displayed a normal flagellum configuration, suggesting that HP0256 was not essential for assembly and polar localisation of the flagella in the cell. Interestingly, whole genome microarrays of an HP0256 mutant revealed transcriptional changes in a number of genes associated with the flagellar regulon and the cell envelope, such as outer membrane proteins and adhesins. Consistent with the array data, lack of the HP0256 gene significantly reduced adhesion and the inflammatory response in host cells. Conclusions We conclude that HP0256 is not a functional counterpart of FliJ in H. pylori. However, it is required for full motility and it is involved, possibly indirectly, in expression of outer membrane proteins and adhesins involved in pathogenesis and adhesion.

  13. DMBT1 expression is down-regulated in breast cancer

    International Nuclear Information System (INIS)

    Braidotti, P; Pietra, GG; Nuciforo, PG; Mollenhauer, J; Poustka, A; Pellegrini, C; Moro, A; Bulfamante, G; Coggi, G; Bosari, S

    2004-01-01

    We studied the expression of DMBT1 (deleted in malignant brain tumor 1), a putative tumor suppressor gene, in normal, proliferative, and malignant breast epithelium and its possible relation to cell cycle. Sections from 17 benign lesions and 55 carcinomas were immunostained with anti DMBT1 antibody (DMBTh12) and sections from 36 samples, were double-stained also with anti MCM5, one of the 6 pre-replicative complex proteins with cell proliferation-licensing functions. DMBT1 gene expression at mRNA level was assessed by RT-PCR in frozen tissues samples from 39 patients. Normal glands and hyperplastic epithelium in benign lesions displayed a luminal polarized DMBTh12 immunoreactivity. Normal and hyperplastic epithelium adjacent to carcinomas showed a loss of polarization, with immunostaining present in basal and perinuclear cytoplasmic compartments. DMBT1 protein expression was down-regulated in the cancerous lesions compared to the normal and/or hyperplastic epithelium adjacent to carcinomas (3/55 positive carcinomas versus 33/42 positive normal/hyperplastic epithelia; p = 0.0001). In 72% of cases RT-PCR confirmed immunohistochemical results. Most of normal and hyperplastic mammary cells positive with DMBTh12 were also MCM5-positive. The redistribution and up-regulation of DMBT1 in normal and hyperplastic tissues flanking malignant tumours and its down-regulation in carcinomas suggests a potential role in breast cancer. Moreover, the concomitant expression of DMTB1 and MCM5 suggests its possible association with the cell-cycle regulation

  14. GDSL LIPASE1 Modulates Plant Immunity through Feedback Regulation of Ethylene Signaling1[W

    Science.gov (United States)

    Kim, Hye Gi; Kwon, Sun Jae; Jang, Young Jin; Nam, Myung Hee; Chung, Joo Hee; Na, Yun-Cheol; Guo, Hongwei; Park, Ohkmae K.

    2013-01-01

    Ethylene is a key signal in the regulation of plant defense responses. It is required for the expression and function of GDSL LIPASE1 (GLIP1) in Arabidopsis (Arabidopsis thaliana), which plays an important role in plant immunity. Here, we explore molecular mechanisms underlying the relationship between GLIP1 and ethylene signaling by an epistatic analysis of ethylene response mutants and GLIP1-overexpressing (35S:GLIP1) plants. We show that GLIP1 expression is regulated by ethylene signaling components and, further, that GLIP1 expression or application of petiole exudates from 35S:GLIP1 plants affects ethylene signaling both positively and negatively, leading to ETHYLENE RESPONSE FACTOR1 activation and ETHYLENE INSENSITIVE3 (EIN3) down-regulation, respectively. Additionally, 35S:GLIP1 plants or their exudates increase the expression of the salicylic acid biosynthesis gene SALICYLIC ACID INDUCTION-DEFICIENT2, known to be inhibited by EIN3 and EIN3-LIKE1. These results suggest that GLIP1 regulates plant immunity through positive and negative feedback regulation of ethylene signaling, and this is mediated by its activity to accumulate a systemic signal(s) in the phloem. We propose a model explaining how GLIP1 regulates the fine-tuning of ethylene signaling and ethylene-salicylic acid cross talk. PMID:24170202

  15. Determination of the approximate number of welding qualification procedures, according to the AD-HP 2/1 and NUCLEN rules

    International Nuclear Information System (INIS)

    Couto, J.G.V.

    1986-01-01

    The simple equations based on the phylosophy of AD-HP 2/1 which determine the approximate number welding qualification procedures for the manufacture either of one component, or several components requested simultaneously are presented. It is also intended to help the manufacturer in the rational preparation of scheduling the required minimum qualifications for performing the work, including giving him an idea about the involved costs which the firm will have to bear in this phase prior to manufacturing. (Author) [pt

  16. The HP 9825 A program for the determination of an isotope half-life

    International Nuclear Information System (INIS)

    Jujuratisbela, Uju.

    1980-01-01

    Determination of half life of gold 198, indium 116, manganese 56, copper 64 are presented, using least squares method in HP 9825 A. This method is more accurate and needs less time than graphic method. (author tr.)

  17. PINK1 positively regulates IL-1β-mediated signaling through Tollip and IRAK1 modulation

    Directory of Open Access Journals (Sweden)

    Lee Hyun Jung

    2012-12-01

    Full Text Available Abstract Background Parkinson disease (PD is characterized by a slow, progressive degeneration of dopaminergic neurons in the substantianigra. The cause of neuronal loss in PD is not well understood, but several genetic loci, including PTEN-induced putative kinase 1 (PINK1, have been linked to early-onset autosomal recessive forms of familial PD. Neuroinflammation greatly contributes to PD neuronal degeneration and pathogenesis. IL-1 is one of the principal cytokines that regulates various immune and inflammatory responses via the activation of the transcription factors NF-κB and activating protein-1. Despite the close relationship between PD and neuroinflammation, the functional roles of PD-linked genes during inflammatory processes remain poorly understood. Methods To explore the functional roles of PINK1 in response to IL-1β stimulation, HEK293 cells, mouse embryonic fibroblasts derived from PINK1-null (PINK1−/− and control (PINK1+/+ mice, and 293 IL-1RI cells stably expressing type 1 IL-1 receptor were used. Immunoprecipitation and western blot analysis were performed to detect protein–protein interaction and protein ubiquitination. To confirm the effect of PINK1 on NF-κB activation, NF-κB-dependent firefly luciferase reporter assay was conducted. Results PINK1 specifically binds two components of the IL-1-mediated signaling cascade, Toll-interacting protein (Tollip and IL-1 receptor-associated kinase 1 (IRAK1. The association of PINK1 with Tollip, a negative regulator of IL-1β signaling, increases upon IL-1β stimulation, which then facilitates the dissociation of Tollip from IRAK1 as well as the assembly of the IRAK1–TNF receptor-associated factor 6 (TRAF6 complex. PINK1 also enhances Lys63-linked polyubiquitination of IRAK1, an essential modification of recruitment of NF-κB essential modulator and subsequent IκB kinase activation, and increases formation of the intermediate signalosome including IRAK1, TRAF6, and

  18. 75 FR 50950 - Federal Speculative Position Limits for Referenced Energy Contracts and Associated Regulations

    Science.gov (United States)

    2010-08-18

    ..., section 4a(a) of the Act authorized the Commission to establish position limits for contracts traded on or... Position Limits for Referenced Energy Contracts and Associated Regulations AGENCY: Commodity Futures... and option contracts based on a limited set of exempt commodities,\\1\\ namely certain energy...

  19. A CAMAC seven-crate system on-line with an HP2116B computer

    International Nuclear Information System (INIS)

    Chernenko, S.P.; Chernykh, E.V.; Filatova, N.A.; Ivanov, A.B.; Kolpakov, I.F.; Nikityuk, N.N.; Smirnov, V.A.; Zanevsky, Yu.V.

    1975-01-01

    A branch of seven CAMAC on-line with an HP2116B computer is described. This system is used for data acquisition from a Cherenkov 90-channel spectrometer, 32 magnetostrictive chambers, 20 registers of the proportional chambers, scalers, and hodoscope registers

  20. Investigation of Trimethyllysine Binding by the HP1 Chromodomain via Unnatural Amino Acid Mutagenesis.

    Science.gov (United States)

    Baril, Stefanie A; Koenig, Amber L; Krone, Mackenzie W; Albanese, Katherine I; He, Cyndi Qixin; Lee, Ga Young; Houk, Kendall N; Waters, Marcey L; Brustad, Eric M

    2017-12-06

    Trimethyllysine (Kme3) reader proteins are targets for inhibition due to their role in mediating gene expression. Although all such reader proteins bind Kme3 in an aromatic cage, the driving force for binding may differ; some readers exhibit evidence for cation-π interactions whereas others do not. We report a general unnatural amino acid mutagenesis approach to quantify the contribution of individual tyrosines to cation binding using the HP1 chromodomain as a model system. We demonstrate that two tyrosines (Y24 and Y48) bind to a Kme3-histone tail peptide via cation-π interactions, but linear free energy trends suggest they do not contribute equally to binding. X-ray structures and computational analysis suggest that the distance and degree of contact between Tyr residues and Kme3 plays an important role in tuning cation-π-mediated Kme3 recognition. Although cation-π interactions have been studied in a number of proteins, this work is the first to utilize direct binding assays, X-ray crystallography, and modeling, to pinpoint factors that influence the magnitude of the individual cation-π interactions.

  1. Goal-Oriented Self-Adaptive hp Finite Element Simulation of 3D DC Borehole Resistivity Simulations

    KAUST Repository

    Calo, Victor M.; Pardo, David; Paszyński, Maciej R.

    2011-01-01

    (adjusting polynomial orders of approximation) or hp (both) refinements on the finite elements. The new parallel implementation utilizes a computational mesh shared between multiple processors. All computational algorithms, including automatic hp goal

  2. Spop promotes skeletal development and homeostasis by positively regulating Ihh signaling.

    Science.gov (United States)

    Cai, Hongchen; Liu, Aimin

    2016-12-20

    Indian Hedgehog (Ihh) regulates chondrocyte and osteoblast differentiation through the Glioma-associated oncogene homolog (Gli) transcription factors. Previous in vitro studies suggested that Speckle-type POZ protein (Spop), part of the Cullin-3 (Cul3) ubiquitin ligase complex, targets Gli2 and Gli3 for degradation and negatively regulates Hedgehog (Hh) signaling. In this study, we found defects in chondrocyte and osteoblast differentiation in Spop-null mutant mice. Strikingly, both the full-length and repressor forms of Gli3, but not Gli2, were up-regulated in Spop mutants, and Ihh target genes Patched 1 (Ptch1) and parathyroid hormone-like peptide (Pthlh) were down-regulated, indicating compromised Hh signaling. Consistent with this finding, reducing Gli3 dosage greatly rescued the Spop mutant skeletal defects. We further show that Spop directly targets the Gli3 repressor for ubiquitination and degradation. Finally, we demonstrate in a conditional mutant that loss of Spop results in brachydactyly and osteopenia, which can be rescued by reducing the dosage of Gli3. In summary, Spop is an important positive regulator of Ihh signaling and skeletal development.

  3. Expression of POEM, a positive regulator of osteoblast differentiation, is suppressed by TNF-α

    International Nuclear Information System (INIS)

    Tsukasaki, Masayuki; Yamada, Atsushi; Suzuki, Dai; Aizawa, Ryo; Miyazono, Agasa; Miyamoto, Yoichi; Suzawa, Tetsuo; Takami, Masamichi; Yoshimura, Kentaro; Morimura, Naoko; Yamamoto, Matsuo; Kamijo, Ryutaro

    2011-01-01

    Highlights: → TNF-α inhibits POEM gene expression. → Inhibition of POEM gene expression is caused by NF-κB activation by TNF-α. → Over-expression of POEM recovers inhibition of osteoblast differentiation by TNF-α. -- Abstract: POEM, also known as nephronectin, is an extracellular matrix protein considered to be a positive regulator of osteoblast differentiation. In the present study, we found that tumor necrosis factor-α (TNF-α), a key regulator of bone matrix properties and composition that also inhibits terminal osteoblast differentiation, strongly inhibited POEM expression in the mouse osteoblastic cell line MC3T3-E1. TNF-α-induced down-regulation of POEM gene expression occurred in both time- and dose-dependent manners through the nuclear factor kappa B (NF-κB) pathway. In addition, expressions of marker genes in differentiated osteoblasts were down-regulated by TNF-α in a manner consistent with our findings for POEM, while over-expression of POEM recovered TNF-α-induced inhibition of osteoblast differentiation. These results suggest that TNF-α inhibits POEM expression through the NF-κB signaling pathway and down-regulation of POEM influences the inhibition of osteoblast differentiation by TNF-α.

  4. Expression of POEM, a positive regulator of osteoblast differentiation, is suppressed by TNF-{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Tsukasaki, Masayuki [Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555 (Japan); Yamada, Atsushi, E-mail: yamadaa@dent.showa-u.ac.jp [Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555 (Japan); Suzuki, Dai [Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555 (Japan); Aizawa, Ryo [Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555 (Japan); Department of Periodontology, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ohta, Tokyo 145-8515 (Japan); Miyazono, Agasa [Department of Periodontology, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ohta, Tokyo 145-8515 (Japan); Miyamoto, Yoichi; Suzawa, Tetsuo; Takami, Masamichi; Yoshimura, Kentaro [Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555 (Japan); Morimura, Naoko [Laboratory for Comparative Neurogenesis, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198 (Japan); Yamamoto, Matsuo [Department of Periodontology, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ohta, Tokyo 145-8515 (Japan); Kamijo, Ryutaro [Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555 (Japan)

    2011-07-15

    Highlights: {yields} TNF-{alpha} inhibits POEM gene expression. {yields} Inhibition of POEM gene expression is caused by NF-{kappa}B activation by TNF-{alpha}. {yields} Over-expression of POEM recovers inhibition of osteoblast differentiation by TNF-{alpha}. -- Abstract: POEM, also known as nephronectin, is an extracellular matrix protein considered to be a positive regulator of osteoblast differentiation. In the present study, we found that tumor necrosis factor-{alpha} (TNF-{alpha}), a key regulator of bone matrix properties and composition that also inhibits terminal osteoblast differentiation, strongly inhibited POEM expression in the mouse osteoblastic cell line MC3T3-E1. TNF-{alpha}-induced down-regulation of POEM gene expression occurred in both time- and dose-dependent manners through the nuclear factor kappa B (NF-{kappa}B) pathway. In addition, expressions of marker genes in differentiated osteoblasts were down-regulated by TNF-{alpha} in a manner consistent with our findings for POEM, while over-expression of POEM recovered TNF-{alpha}-induced inhibition of osteoblast differentiation. These results suggest that TNF-{alpha} inhibits POEM expression through the NF-{kappa}B signaling pathway and down-regulation of POEM influences the inhibition of osteoblast differentiation by TNF-{alpha}.

  5. Genomics of a Metamorphic Timing QTL: met1 Maps to a Unique Genomic Position and Regulates Morph and Species-Specific Patterns of Brain Transcription

    Science.gov (United States)

    Page, Robert B.; Boley, Meredith A.; Kump, David K.; Voss, Stephen R.

    2013-01-01

    Very little is known about genetic factors that regulate life history transitions during ontogeny. Closely related tiger salamanders (Ambystoma species complex) show extreme variation in metamorphic timing, with some species foregoing metamorphosis altogether, an adaptive trait called paedomorphosis. Previous studies identified a major effect quantitative trait locus (met1) for metamorphic timing and expression of paedomorphosis in hybrid crosses between the biphasic Eastern tiger salamander (Ambystoma tigrinum tigrinum) and the paedomorphic Mexican axolotl (Ambystoma mexicanum). We used existing hybrid mapping panels and a newly created hybrid cross to map the met1 genomic region and determine the effect of met1 on larval growth, metamorphic timing, and gene expression in the brain. We show that met1 maps to the position of a urodele-specific chromosome rearrangement on linkage group 2 that uniquely brought functionally associated genes into linkage. Furthermore, we found that more than 200 genes were differentially expressed during larval development as a function of met1 genotype. This list of differentially expressed genes is enriched for proteins that function in the mitochondria, providing evidence of a link between met1, thyroid hormone signaling, and mitochondrial energetics associated with metamorphosis. Finally, we found that met1 significantly affected metamorphic timing in hybrids, but not early larval growth rate. Collectively, our results show that met1 regulates species and morph-specific patterns of brain transcription and life history variation. PMID:23946331

  6. Drosophila atm/telomere fusion is required for telomeric localization of HP1 and telomere position effect

    OpenAIRE

    Oikemus, Sarah R.; McGinnis, Nadine; Queiroz-Machado, Joana; Tukachinsky, Hanna; Takada, Saeko; Sunkel, Claudio E.; Brodsky, Michael H.

    2004-01-01

    Terminal deletions of Drosophila chromosomes can be stably protected from end-to-end fusion despite the absence of all telomere-associated sequences. The sequence-independent protection of these telomeres suggests that recognition of chromosome ends might contribute to the epigenetic protection of telomeres. In mammals, Ataxia Telangiectasia Mutated (ATM) is activated by DNA damage and acts through an unknown, telomerase-independent mechanism to regulate telomere length and protection. We dem...

  7. Holomorphic extension of generalizations of Hp functions

    Directory of Open Access Journals (Sweden)

    Richard D. Carmichael

    1985-01-01

    Full Text Available In recent analysis we have defined and studied holomorphic functions in tubes in ℂn which generalize the Hardy Hp functions in tubes. In this paper we consider functions f(z, z=x+iy, which are holomorphic in the tube TC=ℝn+iC, where C is the finite union of open convex cones Cj, j=1,…,m, and which satisfy the norm growth of our new functions. We prove a holomorphic extension theorem in which f(z, z ϵ TC, is shown to be extendable to a function which is holomorphic in T0(C=ℝn+i0(C, where 0(C is the convex hull of C, if the distributional boundary values in &#x1D4AE;′ of f(z from each connected component TCj of TC are equal.

  8. Seasoning ingredients in a medium-fat diet regulate lipid metabolism in peripheral tissues via the hypothalamic-pituitary axis in growing rats.

    Science.gov (United States)

    Tanaka, Mitsuru; Yasuoka, Akihito; Yoshinuma, Haruka; Saito, Yoshikazu; Asakura, Tomiko; Tanabe, Soichi

    2018-03-01

    We fed rats noodle (N) -diet containing 30 wt.% instant noodle with a 26% fat-to-energy ratio for 30 days (N-group). Compared with rats that were fed the same amount of nutrients (C-group), the N-group showed lower liver triacylglycerol levels and higher fecal cholesterol levels. We then analyzed transcriptome of the hypothalamic-pituitary (HP), the liver and the white adipose tissue (WAT). Thyroid stimulating hormone (Tshb), and its partner, glycoprotein hormone genes were up-regulated in the HP of N-group. Sterol regulatory element binding transcription factors were activated in the liver of N-group, while an up-regulation of the angiogenic signal occurred in the WAT of N-group. N-group showed higher urine noradrenaline (NA) level suggesting that these tissue signals are regulated by NA and Tshb. The N-diet contains 0.326 wt.% glutamate, 0.00236 wt.% 6-shogaol and Maillard reaction products. Our results suggest that these ingredients may affect lipid homeostasis via the HP axis.

  9. Rasputin functions as a positive regulator of orb in Drosophila oogenesis.

    Directory of Open Access Journals (Sweden)

    Alexandre Costa

    Full Text Available The determination of cell fate and the establishment of polarity axes during Drosophila oogenesis depend upon pathways that localize mRNAs within the egg chamber and control their on-site translation. One factor that plays a central role in regulating on-site translation of mRNAs is Orb. Orb is a founding member of the conserved CPEB family of RNA-binding proteins. These proteins bind to target sequences in 3' UTRs and regulate mRNA translation by modulating poly(A tail length. In addition to controlling the translation of axis-determining mRNAs like grk, fs(1K10, and osk, Orb protein autoregulates its own synthesis by binding to orb mRNA and activating its translation. We have previously shown that Rasputin (Rin, the Drosophila homologue of Ras-GAP SH3 Binding Protein (G3BP, associates with Orb in a messenger ribonucleoprotein (mRNP complex. Rin is an evolutionarily conserved RNA-binding protein believed to function as a link between Ras signaling and RNA metabolism. Here we show that Orb and Rin form a complex in the female germline. Characterization of a new rin allele shows that rin is essential for oogenesis. Co-localization studies suggest that Orb and Rin form a complex in the oocyte at different stages of oogenesis. This is supported by genetic and biochemical analyses showing that rin functions as a positive regulator in the orb autoregulatory pathway by increasing Orb protein expression. Tandem Mass Spectrometry analysis shows that several canonical stress granule proteins are associated with the Orb-Rin complex suggesting that a conserved mRNP complex regulates localized translation during oogenesis in Drosophila.

  10. Rasputin functions as a positive regulator of orb in Drosophila oogenesis.

    Science.gov (United States)

    Costa, Alexandre; Pazman, Cecilia; Sinsimer, Kristina S; Wong, Li Chin; McLeod, Ian; Yates, John; Haynes, Susan; Schedl, Paul

    2013-01-01

    The determination of cell fate and the establishment of polarity axes during Drosophila oogenesis depend upon pathways that localize mRNAs within the egg chamber and control their on-site translation. One factor that plays a central role in regulating on-site translation of mRNAs is Orb. Orb is a founding member of the conserved CPEB family of RNA-binding proteins. These proteins bind to target sequences in 3' UTRs and regulate mRNA translation by modulating poly(A) tail length. In addition to controlling the translation of axis-determining mRNAs like grk, fs(1)K10, and osk, Orb protein autoregulates its own synthesis by binding to orb mRNA and activating its translation. We have previously shown that Rasputin (Rin), the Drosophila homologue of Ras-GAP SH3 Binding Protein (G3BP), associates with Orb in a messenger ribonucleoprotein (mRNP) complex. Rin is an evolutionarily conserved RNA-binding protein believed to function as a link between Ras signaling and RNA metabolism. Here we show that Orb and Rin form a complex in the female germline. Characterization of a new rin allele shows that rin is essential for oogenesis. Co-localization studies suggest that Orb and Rin form a complex in the oocyte at different stages of oogenesis. This is supported by genetic and biochemical analyses showing that rin functions as a positive regulator in the orb autoregulatory pathway by increasing Orb protein expression. Tandem Mass Spectrometry analysis shows that several canonical stress granule proteins are associated with the Orb-Rin complex suggesting that a conserved mRNP complex regulates localized translation during oogenesis in Drosophila.

  11. Cumulative nucleon production in 3Hep- and 3Hp interactions at momenta of colliding nuclei 5 GeV/c

    International Nuclear Information System (INIS)

    Abdullin, S.K.; Blinov, A.V.; Vanyushin, I.A.

    1989-01-01

    Inclusive cross sections of cumulative protons produced in 3 Hep- and 3 Hp-interactions under momenta of colliding 5 GeV/c nuclei are investigated. Experimental material is obtained using liquid-hydrogen ITEP chamber-80cm. Under the cumulative proton kinetic energy, exceeding 50 MeV inclusive cross section ratio σ( 3 Hep→pX)/σ( 3 Hp→pX)=1.6±0.1. Within the same energy interval evaluation of yield ratio of cumulative protons and neutrons, produced in 3 Hep -interactions, leads to ∼ 1.6 value. Asymmetry of mean multiple protons escaping forward and backward both in 3 Hep -and in 3 Hp interactions is observed. Averaged invariant distribution functions for cumulative protons and neutrons in 8 Hep-interactions and protons in 3 Hp-interactions are constructed (the averaging is performed within 90-180 deg and 120-180 deg intervals). To temperatures of such distributions are found. 43 refs.; 1 fig

  12. Calcium regulates caveolin-1 expression at the transcriptional level

    International Nuclear Information System (INIS)

    Yang, Xiao-Yan; Huang, Cheng-Cheng; Kan, Qi-Ming; Li, Yan; Liu, Dan; Zhang, Xue-Cheng; Sato, Toshinori; Yamagata, Sadako; Yamagata, Tatsuya

    2012-01-01

    Highlights: ► Caveolin-1 expression is regulated by calcium signaling at the transcriptional level. ► An inhibitor of or siRNA to L-type calcium channel suppressed caveolin-1 expression. ► Cyclosporine A or an NFAT inhibitor markedly reduced caveolin-1 expression. ► Caveolin-1 regulation by calcium signaling is observed in several mouse cell lines. -- Abstract: Caveolin-1, an indispensable component of caveolae serving as a transformation suppressor protein, is highly expressed in poorly metastatic mouse osteosarcoma FBJ-S1 cells while highly metastatic FBJ-LL cells express low levels of caveolin-1. Calcium concentration is higher in FBJ-S1 cells than in FBJ-LL cells; therefore, we investigated the possibility that calcium signaling positively regulates caveolin-1 in mouse FBJ-S1 cells. When cells were treated with the calcium channel blocker nifedipine, cyclosporin A (a calcineurin inhibitor), or INCA-6 (a nuclear factor of activated T-cells [NFAT] inhibitor), caveolin-1 expression at the mRNA and protein levels decreased. RNA silencing of voltage-dependent L-type calcium channel subunit alpha-1C resulted in suppression of caveolin-1 expression. This novel caveolin-1 regulation pathway was also identified in mouse NIH 3T3 cells and Lewis lung carcinoma cells. These results indicate that caveolin-1 is positively regulated at the transcriptional level through a novel calcium signaling pathway mediated by L-type calcium channel/Ca 2+ /calcineurin/NFAT.

  13. Modeling of Yield Estimation for The Main Crops in Iran Based on Mechanization Index (hp ha-1

    Directory of Open Access Journals (Sweden)

    K Abbasi

    2014-09-01

    Full Text Available Agricultural mechanization is a method for transiting from traditional agriculture towards industrial and sustainable one. Due to the limitation of natural resources and increasing population we need to have economical production of agricultural crops. For reaching this destination; agricultural mechanization has a remarkable role. So it is necessary to have an extensive view for mechanization, because with the help of mechanization the agricultural inputs such as seeds, fertilizer and even water and soil can effectively be managed for an economical and sustainable production. This study has been carried out in many provinces of Iran. The data of agricultural tractors and cereal combine harvesters were firstly gathered by means of questionnaire. The tractors were categorized in four power levels of less than 45, 45 to 80, 80 to 110, and more than 110 hp. In addition, it was also carried out for cereal combine harvesters; it was in three power levels, i.e. between 100 to 110, 110 to 155 and 155 to 210 horse-power in 3 ages, i.e. less than 13, between 13 to 20, and more than 20 years. Information regarding to cultivation areas, production volume, and yield of main crops gathered from statistics of Ministry of Jihad-e-Agriculture. Then agriculture mechanization level index (hp ha-1 in each province was calculated. Four main crops including irrigated and rain-fed wheat and irrigated and rain-fed barley, which met the required criteria to be used in the model, were statistically analyzed. Correlation analysis was carried out in order to get an effective model between yield of the four main crops in Iran and agriculture mechanization level index. Pearson correlation index showed that there is a direct and significant correlation between these variables. Subsequently, outliers were identified in order to get a model with necessary efficiency to predict the yield through mechanization level index, by scatter diagram and estimating regression lines in 1

  14. ASM-3 acid sphingomyelinase functions as a positive regulator of the DAF-2/AGE-1 signaling pathway and serves as a novel anti-aging target.

    Directory of Open Access Journals (Sweden)

    Yongsoon Kim

    Full Text Available In C. elegans, the highly conserved DAF-2/insulin/insulin-like growth factor 1 receptor signaling (IIS pathway regulates longevity, metabolism, reproduction and development. In mammals, acid sphingomyelinase (ASM is an enzyme that hydrolyzes sphingomyelin to produce ceramide. ASM has been implicated in CD95 death receptor signaling under certain stress conditions. However, the involvement of ASM in growth factor receptor signaling under physiological conditions is not known. Here, we report that in vivo ASM functions as a positive regulator of the DAF-2/IIS pathway in C. elegans. We have shown that inactivation of asm-3 extends animal lifespan and promotes dauer arrest, an alternative developmental process. A significant cooperative effect on lifespan is observed between asm-3 deficiency and loss-of-function alleles of the age-1/PI 3-kinase, with the asm-3; age-1 double mutant animals having a mean lifespan 259% greater than that of the wild-type animals. The lifespan extension phenotypes caused by the loss of asm-3 are dependent on the functions of daf-16/FOXO and daf-18/PTEN. We have demonstrated that inactivation of asm-3 causes nuclear translocation of DAF-16::GFP protein, up-regulates endogenous DAF-16 protein levels and activates the downstream targeting genes of DAF-16. Together, our findings reveal a novel role of asm-3 in regulation of lifespan and diapause by modulating IIS pathway. Importantly, we have found that two drugs known to inhibit mammalian ASM activities, desipramine and clomipramine, markedly extend the lifespan of wild-type animals, in a manner similar to that achieved by genetic inactivation of the asm genes. Our studies illustrate a novel strategy of anti-aging by targeting ASM, which may potentially be extended to mammals.

  15. ASM-3 acid sphingomyelinase functions as a positive regulator of the DAF-2/AGE-1 signaling pathway and serves as a novel anti-aging target.

    Science.gov (United States)

    Kim, Yongsoon; Sun, Hong

    2012-01-01

    In C. elegans, the highly conserved DAF-2/insulin/insulin-like growth factor 1 receptor signaling (IIS) pathway regulates longevity, metabolism, reproduction and development. In mammals, acid sphingomyelinase (ASM) is an enzyme that hydrolyzes sphingomyelin to produce ceramide. ASM has been implicated in CD95 death receptor signaling under certain stress conditions. However, the involvement of ASM in growth factor receptor signaling under physiological conditions is not known. Here, we report that in vivo ASM functions as a positive regulator of the DAF-2/IIS pathway in C. elegans. We have shown that inactivation of asm-3 extends animal lifespan and promotes dauer arrest, an alternative developmental process. A significant cooperative effect on lifespan is observed between asm-3 deficiency and loss-of-function alleles of the age-1/PI 3-kinase, with the asm-3; age-1 double mutant animals having a mean lifespan 259% greater than that of the wild-type animals. The lifespan extension phenotypes caused by the loss of asm-3 are dependent on the functions of daf-16/FOXO and daf-18/PTEN. We have demonstrated that inactivation of asm-3 causes nuclear translocation of DAF-16::GFP protein, up-regulates endogenous DAF-16 protein levels and activates the downstream targeting genes of DAF-16. Together, our findings reveal a novel role of asm-3 in regulation of lifespan and diapause by modulating IIS pathway. Importantly, we have found that two drugs known to inhibit mammalian ASM activities, desipramine and clomipramine, markedly extend the lifespan of wild-type animals, in a manner similar to that achieved by genetic inactivation of the asm genes. Our studies illustrate a novel strategy of anti-aging by targeting ASM, which may potentially be extended to mammals.

  16. ASM-3 Acid Sphingomyelinase Functions as a Positive Regulator of the DAF-2/AGE-1 Signaling Pathway and Serves as a Novel Anti-Aging Target

    Science.gov (United States)

    Kim, Yongsoon; Sun, Hong

    2012-01-01

    In C. elegans, the highly conserved DAF-2/insulin/insulin-like growth factor 1 receptor signaling (IIS) pathway regulates longevity, metabolism, reproduction and development. In mammals, acid sphingomyelinase (ASM) is an enzyme that hydrolyzes sphingomyelin to produce ceramide. ASM has been implicated in CD95 death receptor signaling under certain stress conditions. However, the involvement of ASM in growth factor receptor signaling under physiological conditions is not known. Here, we report that in vivo ASM functions as a positive regulator of the DAF-2/IIS pathway in C. elegans. We have shown that inactivation of asm-3 extends animal lifespan and promotes dauer arrest, an alternative developmental process. A significant cooperative effect on lifespan is observed between asm-3 deficiency and loss-of-function alleles of the age-1/PI 3-kinase, with the asm-3; age-1 double mutant animals having a mean lifespan 259% greater than that of the wild-type animals. The lifespan extension phenotypes caused by the loss of asm-3 are dependent on the functions of daf-16/FOXO and daf-18/PTEN. We have demonstrated that inactivation of asm-3 causes nuclear translocation of DAF-16::GFP protein, up-regulates endogenous DAF-16 protein levels and activates the downstream targeting genes of DAF-16. Together, our findings reveal a novel role of asm-3 in regulation of lifespan and diapause by modulating IIS pathway. Importantly, we have found that two drugs known to inhibit mammalian ASM activities, desipramine and clomipramine, markedly extend the lifespan of wild-type animals, in a manner similar to that achieved by genetic inactivation of the asm genes. Our studies illustrate a novel strategy of anti-aging by targeting ASM, which may potentially be extended to mammals. PMID:23049887

  17. Spatially adaptive hp refinement approach for PN neutron transport equation using spectral element method

    International Nuclear Information System (INIS)

    Nahavandi, N.; Minuchehr, A.; Zolfaghari, A.; Abbasi, M.

    2015-01-01

    Highlights: • Powerful hp-SEM refinement approach for P N neutron transport equation has been presented. • The method provides great geometrical flexibility and lower computational cost. • There is a capability of using arbitrary high order and non uniform meshes. • Both posteriori and priori local error estimation approaches have been employed. • High accurate results are compared against other common adaptive and uniform grids. - Abstract: In this work we presented the adaptive hp-SEM approach which is obtained from the incorporation of Spectral Element Method (SEM) and adaptive hp refinement. The SEM nodal discretization and hp adaptive grid-refinement for even-parity Boltzmann neutron transport equation creates powerful grid refinement approach with high accuracy solutions. In this regard a computer code has been developed to solve multi-group neutron transport equation in one-dimensional geometry using even-parity transport theory. The spatial dependence of flux has been developed via SEM method with Lobatto orthogonal polynomial. Two commonly error estimation approaches, the posteriori and the priori has been implemented. The incorporation of SEM nodal discretization method and adaptive hp grid refinement leads to high accurate solutions. Coarser meshes efficiency and significant reduction of computer program runtime in comparison with other common refining methods and uniform meshing approaches is tested along several well-known transport benchmarks

  18. Fate and transport of mercury in soil systems : a numerical model in HP1 and sensitivity analysis

    Science.gov (United States)

    Leterme, Bertrand; Jacques, Diederik

    2013-04-01

    Mercury (Hg) poses threats for human health and the environment, notably due to its persistence and its ability to bioaccumulate in ecosystems. Anthropogenic activities are major contributors of mercury release to soils. Main sources of contamination include manufacturing (chlor-alkali plants, manometer spill), mine tailings from mercury, gold and silver mining industries, wood preservation. The objective of this study was to develop a reactive transport model for simulating mercury fate and transport in the unsaturated zone, and to gain insight in the fate and transport of Hg following anthropogenic soil contamination. The present work is done in the framework of the IMaHg project, which aims at providing recommendations to improve management of sites contaminated by mercury within the SNOWMAN funding framework. A model of mercury fate and transport in soil systems was developed using the reactive transport code HP1 (Jacques and Šimůnek, 2010). The geochemical database THERMODDEM (Blanc et al., 2012) is used, augmented with some speciation data from (Skyllberg, 2012). The main processes accounted for in the model are : Hg aqueous speciation (including complexation with dissolved organic matter (DOM) - humic and fulvic acids, and thiol groups), Hg sorption to solid organic matter (SOM), dissolution of solid phase Hg (e.g. cinnabar HgS(s)), dissolution of Hg non-aqueous liquid phase (NAPL), sunlight-driven Hg(II) reduction to Hg(0), Hg(0) diffusion in the gas phase and volatilization, DOM sorption to soil minerals. Colloid facilitated transport is implicitly accounted for by solute transport of Hg-DOM complexes. Because we focused on soil systems having a high Hg contamination, some processes showing relatively smaller Hg fluxes could be neglected such as vegetation uptake and atmospheric wet and dry deposition. NAPL migration and entrapment is not modelled, as pollution is assumed to be historical and only residual NAPL to be present. Mercury methylation and

  19. Effect of a long-chained fructan Raftiline HP on blood lipids and spontaneous atherosclerosis in low density receptor knockout mice

    DEFF Research Database (Denmark)

    Mortensen, Alicja; Poulsen, Morten; Frandsen, Henrik Lauritz

    2002-01-01

    The effect of a long-chained fructan Raftiline HP on spontaneous hypercholesterolemia and atherosclerosis was studied in 40 LDLR-/- male mice receiving isocaloric, balanced in fat content, purified diets with 0 or 10% Raftiline HP, for 16 weeks. The feed intake was comparable (3.9 v. 3.8 g/day) b...

  20. Regulation of BAZ1A and nucleosome positioning in the nucleus accumbens in response to cocaine.

    Science.gov (United States)

    Sun, HaoSheng; Damez-Werno, Diane M; Scobie, Kimberly N; Shao, Ning-Yi; Dias, Caroline; Rabkin, Jacqui; Wright, Katherine N; Mouzon, Ezekiell; Kabbaj, Mohamed; Neve, Rachael; Turecki, Gustavo; Shen, Li; Nestler, Eric J

    2017-06-14

    Chromatin regulation, in particular ATP-dependent chromatin remodelers, have previously been shown to be important in the regulation of reward-related behaviors in animal models of mental illnesses. Here we demonstrate that BAZ1A, an accessory subunit of the ISWI family of chromatin remodeling complexes, is downregulated in the nucleus accumbens (NAc) of mice exposed repeatedly to cocaine and of cocaine-addicted humans. Viral-mediated overexpression of BAZ1A in mouse NAc reduces cocaine reward as assessed by conditioned place preference (CPP), but increases cocaine-induced locomotor activation. Furthermore, we investigate nucleosome repositioning genome-wide by conducting chromatin immunoprecipitation (ChIP)-sequencing for total H3 in NAc of control mice and after repeated cocaine administration, and find extensive nucleosome occupancy and shift changes across the genome in response to cocaine exposure. These findings implicate BAZ1A in molecular and behavioral plasticity to cocaine and offer new insight into the pathophysiology of cocaine addiction. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Animation company "Fast Forwards" production with HP Utility Data Center; film built using Adaptive Enterprise framework enabled by shared, virtual resource

    CERN Multimedia

    2003-01-01

    Hewlett Packard have produced a commercial-quality animated film using an experimental rendering service from HP Labs and running on an HP Utility Data Center (UDC). The project demonstrates how computing resources can be managed virtually and illustrates the value of utility computing, in which an end-user taps into a large pool of virtual resources, but pays only for what is used (1 page).

  2. Genome-wide analysis reveals the extent of EAV-HP integration in domestic chicken.

    Science.gov (United States)

    Wragg, David; Mason, Andrew S; Yu, Le; Kuo, Richard; Lawal, Raman A; Desta, Takele Taye; Mwacharo, Joram M; Cho, Chang-Yeon; Kemp, Steve; Burt, David W; Hanotte, Olivier

    2015-10-14

    EAV-HP is an ancient retrovirus pre-dating Gallus speciation, which continues to circulate in modern chicken populations, and led to the emergence of avian leukosis virus subgroup J causing significant economic losses to the poultry industry. We mapped EAV-HP integration sites in Ethiopian village chickens, a Silkie, Taiwan Country chicken, red junglefowl Gallus gallus and several inbred experimental lines using whole-genome sequence data. An average of 75.22 ± 9.52 integration sites per bird were identified, which collectively group into 279 intervals of which 5 % are common to 90 % of the genomes analysed and are suggestive of pre-domestication integration events. More than a third of intervals are specific to individual genomes, supporting active circulation of EAV-HP in modern chickens. Interval density is correlated with chromosome length (P < 2.31(-6)), and 27 % of intervals are located within 5 kb of a transcript. Functional annotation clustering of genes reveals enrichment for immune-related functions (P < 0.05). Our results illustrate a non-random distribution of EAV-HP in the genome, emphasising the importance it may have played in the adaptation of the species, and provide a platform from which to extend investigations on the co-evolutionary significance of endogenous retroviral genera with their hosts.

  3. Weighted curve-fitting program for the HP 67/97 calculator

    International Nuclear Information System (INIS)

    Stockli, M.P.

    1983-01-01

    The HP 67/97 calculator provides in its standard equipment a curve-fit program for linear, logarithmic, exponential and power functions that is quite useful and popular. However, in more sophisticated applications, proper weights for data are often essential. For this purpose a program package was created which is very similar to the standard curve-fit program but which includes the weights of the data for proper statistical analysis. This allows accurate calculation of the uncertainties of the fitted curve parameters as well as the uncertainties of interpolations or extrapolations, or optionally the uncertainties can be normalized with chi-square. The program is very versatile and allows one to perform quite difficult data analysis in a convenient way with the pocket calculator HP 67/97

  4. Tinker-HP: a massively parallel molecular dynamics package for multiscale simulations of large complex systems with advanced point dipole polarizable force fields.

    Science.gov (United States)

    Lagardère, Louis; Jolly, Luc-Henri; Lipparini, Filippo; Aviat, Félix; Stamm, Benjamin; Jing, Zhifeng F; Harger, Matthew; Torabifard, Hedieh; Cisneros, G Andrés; Schnieders, Michael J; Gresh, Nohad; Maday, Yvon; Ren, Pengyu Y; Ponder, Jay W; Piquemal, Jean-Philip

    2018-01-28

    We present Tinker-HP, a massively MPI parallel package dedicated to classical molecular dynamics (MD) and to multiscale simulations, using advanced polarizable force fields (PFF) encompassing distributed multipoles electrostatics. Tinker-HP is an evolution of the popular Tinker package code that conserves its simplicity of use and its reference double precision implementation for CPUs. Grounded on interdisciplinary efforts with applied mathematics, Tinker-HP allows for long polarizable MD simulations on large systems up to millions of atoms. We detail in the paper the newly developed extension of massively parallel 3D spatial decomposition to point dipole polarizable models as well as their coupling to efficient Krylov iterative and non-iterative polarization solvers. The design of the code allows the use of various computer systems ranging from laboratory workstations to modern petascale supercomputers with thousands of cores. Tinker-HP proposes therefore the first high-performance scalable CPU computing environment for the development of next generation point dipole PFFs and for production simulations. Strategies linking Tinker-HP to Quantum Mechanics (QM) in the framework of multiscale polarizable self-consistent QM/MD simulations are also provided. The possibilities, performances and scalability of the software are demonstrated via benchmarks calculations using the polarizable AMOEBA force field on systems ranging from large water boxes of increasing size and ionic liquids to (very) large biosystems encompassing several proteins as well as the complete satellite tobacco mosaic virus and ribosome structures. For small systems, Tinker-HP appears to be competitive with the Tinker-OpenMM GPU implementation of Tinker. As the system size grows, Tinker-HP remains operational thanks to its access to distributed memory and takes advantage of its new algorithmic enabling for stable long timescale polarizable simulations. Overall, a several thousand-fold acceleration over

  5. A High Phosphorus Diet Affects Lipid Metabolism in Rat Liver: A DNA Microarray Analysis

    Science.gov (United States)

    Chun, Sunwoo; Bamba, Takeshi; Suyama, Tatsuya; Ishijima, Tomoko; Fukusaki, Eiichiro; Abe, Keiko; Nakai, Yuji

    2016-01-01

    A high phosphorus (HP) diet causes disorders of renal function, bone metabolism, and vascular function. We previously demonstrated that DNA microarray analysis is an appropriate method to comprehensively evaluate the effects of a HP diet on kidney dysfunction such as calcification, fibrillization, and inflammation. We reported that type IIb sodium-dependent phosphate transporter is significantly up-regulated in this context. In the present study, we performed DNA microarray analysis to investigate the effects of a HP diet on the liver, which plays a pivotal role in energy metabolism. DNA microarray analysis was performed with total RNA isolated from the livers of rats fed a control diet (containing 0.3% phosphorus) or a HP diet (containing 1.2% phosphorus). Gene Ontology analysis of differentially expressed genes (DEGs) revealed that the HP diet induced down-regulation of genes involved in hepatic amino acid catabolism and lipogenesis, while genes related to fatty acid β-oxidation process were up-regulated. Although genes related to fatty acid biosynthesis were down-regulated in HP diet-fed rats, genes important for the elongation and desaturation reactions of omega-3 and -6 fatty acids were up-regulated. Concentrations of hepatic arachidonic acid and eicosapentaenoic acid were increased in HP diet-fed rats. These essential fatty acids activate peroxisome proliferator-activated receptor alpha (PPARα), a transcription factor for fatty acid β-oxidation. Evaluation of the upstream regulators of DEGs using Ingenuity Pathway Analysis indicated that PPARα was activated in the livers of HP diet-fed rats. Furthermore, the serum concentration of fibroblast growth factor 21, a hormone secreted from the liver that promotes fatty acid utilization in adipose tissue as a PPARα target gene, was higher (p = 0.054) in HP diet-fed rats than in control diet-fed rats. These data suggest that a HP diet enhances energy expenditure through the utilization of free fatty acids

  6. A High Phosphorus Diet Affects Lipid Metabolism in Rat Liver: A DNA Microarray Analysis.

    Directory of Open Access Journals (Sweden)

    Sunwoo Chun

    Full Text Available A high phosphorus (HP diet causes disorders of renal function, bone metabolism, and vascular function. We previously demonstrated that DNA microarray analysis is an appropriate method to comprehensively evaluate the effects of a HP diet on kidney dysfunction such as calcification, fibrillization, and inflammation. We reported that type IIb sodium-dependent phosphate transporter is significantly up-regulated in this context. In the present study, we performed DNA microarray analysis to investigate the effects of a HP diet on the liver, which plays a pivotal role in energy metabolism. DNA microarray analysis was performed with total RNA isolated from the livers of rats fed a control diet (containing 0.3% phosphorus or a HP diet (containing 1.2% phosphorus. Gene Ontology analysis of differentially expressed genes (DEGs revealed that the HP diet induced down-regulation of genes involved in hepatic amino acid catabolism and lipogenesis, while genes related to fatty acid β-oxidation process were up-regulated. Although genes related to fatty acid biosynthesis were down-regulated in HP diet-fed rats, genes important for the elongation and desaturation reactions of omega-3 and -6 fatty acids were up-regulated. Concentrations of hepatic arachidonic acid and eicosapentaenoic acid were increased in HP diet-fed rats. These essential fatty acids activate peroxisome proliferator-activated receptor alpha (PPARα, a transcription factor for fatty acid β-oxidation. Evaluation of the upstream regulators of DEGs using Ingenuity Pathway Analysis indicated that PPARα was activated in the livers of HP diet-fed rats. Furthermore, the serum concentration of fibroblast growth factor 21, a hormone secreted from the liver that promotes fatty acid utilization in adipose tissue as a PPARα target gene, was higher (p = 0.054 in HP diet-fed rats than in control diet-fed rats. These data suggest that a HP diet enhances energy expenditure through the utilization of free fatty

  7. Arbitrary-Level Hanging Nodes and Automatic Adaptivity in the hp-FEM

    Czech Academy of Sciences Publication Activity Database

    Šolín, Pavel; Červený, Jakub; Doležel, Ivo

    2008-01-01

    Roč. 77, č. 1 (2008), s. 117-132 ISSN 0378-4754 R&D Projects: GA ČR(CZ) GA102/07/0496; GA ČR GA102/05/0629; GA AV ČR IAA100760702 Institutional research plan: CEZ:AV0Z20570509 Keywords : constrained approximation * hanging nodes * hp-FEM Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 0.930, year: 2008

  8. Assessment of reproductive and developmental effects of DINP, DnHP and DCHP using quantitative weight of evidence.

    Science.gov (United States)

    Dekant, Wolfgang; Bridges, James

    2016-11-01

    Quantitative weight of evidence (QWoE) methodology utilizes detailed scoring sheets to assess the quality/reliability of each publication on toxicity of a chemical and gives numerical scores for quality and observed toxicity. This QWoE-methodology was applied to the reproductive toxicity data on diisononylphthalate (DINP), di-n-hexylphthalate (DnHP), and dicyclohexylphthalate (DCHP) to determine if the scientific evidence for adverse effects meets the requirements for classification as reproductive toxicants. The scores for DINP were compared to those when applying the methodology DCHP and DnHP that have harmonized classifications. Based on the quality/reliability scores, application of the QWoE shows that the three databases are of similar quality; but effect scores differ widely. Application of QWoE to DINP studies resulted in an overall score well below the benchmark required to trigger classification. For DCHP, the QWoE also results in low scores. The high scores from the application of the QWoE methodology to the toxicological data for DnHP represent clear evidence for adverse effects and justify a classification of DnHP as category 1B for both development and fertility. The conclusions on classification based on the QWoE are well supported using a narrative assessment of consistency and biological plausibility. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  9. One step ahead of technology Cern and HP - an ideal team project

    CERN Multimedia

    Garvey, Kelsey

    2009-01-01

    "In 2004, the It team at Cern recognized the comprehensiveness and future of the LHC Computing Grid Project and realized that the IT infrastructures were not sufficient enough to manage the data. Cern therefore partnered with HP ProCurve the following year to minimize the day-to-day workload and improve infrastructure for data output" (1 page)

  10. HP-67 calculator programs for thermodynamic data and phase diagram calculations

    International Nuclear Information System (INIS)

    Brewer, L.

    1978-01-01

    This report is a supplement to a tabulation of the thermodynamic and phase data for the 100 binary systems of Mo with the elements from H to Lr. The calculations of thermodynamic data and phase equilibria were carried out from 5000 0 K to low temperatures. This report presents the methods of calculation used. The thermodynamics involved is rather straightforward and the reader is referred to any advanced thermodynamic text. The calculations were largely carried out using an HP-65 programmable calculator. In this report, those programs are reformulated for use with the HP-67 calculator; great reduction in the number of programs required to carry out the calculation results

  11. pHP-Tethered N-Acyl Carbamate: A Photocage for Nicotinamide.

    Science.gov (United States)

    Salahi, Farbod; Purohit, Vatsal; Ferraudi, Guillermo; Stauffacher, Cynthia; Wiest, Olaf; Helquist, Paul

    2018-05-04

    The synthesis of a new photocaged nicotinamide having an N-acyl carbamate linker and a p-hydroxyphenacyl (pHP) chromophore is described. The photophysical and photochemical studies showed an absorption maximum at λ = 330 nm and a quantum yield for release of 11% that are dependent upon both pH and solvent. While the acyl carbamate releases nicotinamide efficiently, a simpler amide linker was inert to photocleavage. This photocaged nicotinamide has significant advantages with respect to quantum yield, absorbance wavelength, rate of release, and solubility that make it the first practical example of a photocaged amide.

  12. Lactobacillus fermentum HP3-Mediated Fermented Hericium erinaceus Juice as a Health Promoting Food Supplement to Manage Diabetes Mellitus.

    Science.gov (United States)

    Chaiyasut, Chaiyavat; Woraharn, Sasimar; Sivamaruthi, Bhagavathi Sundaram; Lailerd, Narissara; Kesika, Periyanaina; Peerajan, Sartjin

    2018-01-01

    The current study investigated the antidiabetic property of Lactobacillus fermentum HP3-mediated fermented Hericium erinaceus juice (FHJ) using male Wistar rats with streptozotocin-induced diabetes mellitus (DM). FHJ was prepared using boiled mushroom juice and L. fermentum HP3. Amino acid and γ-aminobutyric acid (GABA) content of FHJ was analyzed. Streptozotocin-induced DM rats were supplemented with FHJ in a pre- and posttreatment method. The changes in plasma insulin, plasma glucose level, glycated hemoglobin (HbA1c), representative cytokines, and the antioxidant system were assessed in experimental rats using spectrophotometric methods and enzyme-linked immunosorbent assay. The supplementation of FHJ improved the body mass, insulin level, and recovery progress of hyperglycemia. HbA1c level was altered by the FHJ intervention. The inflammatory cytokines level was suppressed in FHJ supplemented group compared with control. Intervention of FHJ and insulin improved the production of interleukin-10 and transforming growth factor--β1 in DM rat. The study suggested that fermented H erinaceus juice may be used as one of the food-based health-promoting supplement to manage DM along with medication.

  13. The pioneer factor PBX1 is a novel driver of metastatic progression in ERα-positive breast cancer

    Science.gov (United States)

    Magnani, Luca; Patten, Darren K.; Nguyen, Van T.M.; Hong, Sung-Pil; Steel, Jennifer H.; Patel, Naina; Lombardo, Ylenia; Faronato, Monica; Gomes, Ana R.; Woodley, Laura; Page, Karen; Guttery, David; Primrose, Lindsay; Garcia, Daniel Fernandez; Shaw, Jacqui; Viola, Patrizia; Green, Andrew; Nolan, Christopher; Ellis, Ian O.; Rakha, Emad A.; Shousha, Sami; Lam, Eric W.-F.; Győrffy, Balázs; Lupien, Mathieu; Coombes, R. Charles

    2015-01-01

    Over 30% of ERα breast cancer patients develop relapses and progress to metastatic disease despite treatment with endocrine therapies. The pioneer factor PBX1 translates epigenetic cues and mediates estrogen induced ERα binding. Here we demonstrate that PBX1 plays a central role in regulating the ERα transcriptional response to epidermal growth factor (EGF) signaling. PBX1 regulates a subset of EGF-ERα genes highly expressed in aggressive breast tumours. Retrospective stratification of luminal patients using PBX1 protein levels in primary cancer further demonstrates that elevated PBX1 protein levels correlate with earlier metastatic progression. In agreement, PBX1 protein levels are significantly upregulated during metastatic progression in ERα-positive breast cancer patients. Finally we reveal that PBX1 upregulation in aggressive tumours is partly mediated by genomic amplification of the PBX1 locus. Correspondingly, ERα-positive breast cancer patients carrying PBX1 amplification are characterized by poor survival. Notably, we demonstrate that PBX1 amplification can be identified in tumor derived-circulating free DNA of ERα-positive metastatic patients. Metastatic patients with PBX1 amplification are also characterized by shorter relapse-free survival. Our data identifies PBX1 amplification as a functional hallmark of aggressive ERα-positive breast cancers. Mechanistically, PBX1 amplification impinges on several critical pathways associated with aggressive ERα-positive breast cancer. PMID:26215677

  14. Measurement of personal equivalent dose Hp(3) during procedures involving in positron emission tomography; Medida del equivalente de dosis personal en cristalino Hp(3) durante los procedimientos asociados a la tomografía por emisión de positrones

    Energy Technology Data Exchange (ETDEWEB)

    Guiu Souto, J.; Sánchez García, M.; Vázquez, R.; Pardo Montero, J.; Pombar Cameán, M.

    2017-11-01

    The aim of the present study consists to determinate the personal equivalent dose Hp(3) at eye lens during the procedures involved in positron emission tomography. We have monitored the nurse's staff which is responsible of handling and dispensing 18F. We characterize the relevant stages as the preparation, the transport and the administration of monodose syringes in terms of occupational dose. We observed that the preparation presents a major contribution to the occupational doses than the other stages. In addition, during those stage there is a correlation between the dose increments and handling activity. To establish the eye lens dose we use the following dosimetry set: a direct readout solid state dosimeter for general purposes calibrated at Hp(10) and a set of thermolumiscent dosimeters specific for 18F calibrated at Hp(3). Finally, for the dose intercomparison between above dosimeters we obtain a correction factor by Monte Carlo. The eye lens dose, with a value of 2.8 ± 0.4 mSv/yr, results more critical than the dose obtained in other locations, as extremities. [Spanish] El propósito del presente trabajo consiste en la determinación del equivalente de dosis personal Hp(3) en cristalino durante los procedimientos asociados a la tomografía por emisión de positrones. Se ha monitorizado al personal de enfermería que realiza las tareas de manipulación y dispensación del 18F. Se ha realizado un estudio caracterizando la dosis en las etapas más relevantes del procedimiento: la preparación manual de las jeringuillas, el transporte de las mismas y su posterior administración al paciente. Se observó que la preparación es la etapa que más contribuye a la dosis ocupacional, además durante dicha etapa se observa una clara correlación entre el incremento de dosis y la actividad manipulada. Para determinar la dosis en cristalino se ha utilizado el siguiente equipo dosimétrico: un detector de estado sólido de lectura directa de propósito general

  15. Positive words or negative words: whose valence strength are we more sensitive to?

    Science.gov (United States)

    Yang, Jiemin; Zeng, Jing; Meng, Xianxin; Zhu, Liping; Yuan, Jiajin; Li, Hong; Yusoff, Nasir

    2013-10-02

    The present study investigates the human brains' sensitivity to the valence strength of emotionally positive and negative chinese words. Event-Related Potentials were recorded, in two different experimental sessions, for Highly Positive (HP), Mildly Positive (MP) and neutral (NP) words and for Highly Negative (HN), Mildly Negative (MN) and neutral (NN) words, while subjects were required to count the number of words, irrespective of word meanings. The results showed a significant emotion effect in brain potentials for both HP and MP words, and the emotion effect occurred faster for HP words than MP words: HP words elicited more negative deflections than NP words in N2 (250-350 ms) and P3 (350-500 ms) amplitudes, while MP words elicited a significant emotion effect in P3, but not in N2, amplitudes. By contrast, HN words elicited larger amplitudes than NN words in N2 but not in P3 amplitudes, whereas MN words produced no significant emotion effect across N2 and P3 components. Moreover, the size of emotion-neutral differences in P3 amplitudes was significantly larger for MP compared to MN words. Thus, the human brain is reactive to both highly and mildly positive words, and this reactivity increased with the positive valence strength of the words. Conversely, the brain is less reactive to the valence of negative relative to positive words. These results suggest that human brains are equipped with increased sensitivity to the valence strength of positive compared to negative words, a type of emotional stimuli that are well known for reduced arousal. © 2013 Elsevier B.V. All rights reserved.

  16. DYRK1A Is a Regulator of S-Phase Entry in Hepatic Progenitor Cells.

    Science.gov (United States)

    Kruitwagen, Hedwig S; Westendorp, Bart; Viebahn, Cornelia S; Post, Krista; van Wolferen, Monique E; Oosterhoff, Loes A; Egan, David A; Delabar, Jean-Maurice; Toussaint, Mathilda J; Schotanus, Baukje A; de Bruin, Alain; Rothuizen, Jan; Penning, Louis C; Spee, Bart

    2018-01-15

    Hepatic progenitor cells (HPCs) are adult liver stem cells that act as second line of defense in liver regeneration. They are normally quiescent, but in case of severe liver damage, HPC proliferation is triggered by external activation mechanisms from their niche. Although several important proproliferative mechanisms have been described, it is not known which key intracellular regulators govern the switch between HPC quiescence and active cell cycle. We performed a high-throughput kinome small interfering RNA (siRNA) screen in HepaRG cells, a HPC-like cell line, and evaluated the effect on proliferation with a 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay. One hit increased the percentage of EdU-positive cells after knockdown: dual specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A). Although upon DYRK1A silencing, the percentage of EdU- and phosphorylated histone H3 (pH3)-positive cells was increased, and total cell numbers were not increased, possibly through a subsequent delay in cell cycle progression. This phenotype was confirmed with chemical inhibition of DYRK1A using harmine and with primary HPCs cultured as liver organoids. DYRK1A inhibition impaired Dimerization Partner, RB-like, E2F, and multivulva class B (DREAM) complex formation in HPCs and abolished its transcriptional repression on cell cycle progression. To further analyze DYRK1A function in HPC proliferation, liver organoid cultures were established from mBACtgDyrk1A mice, which harbor one extra copy of the murine Dyrk1a gene (Dyrk+++). Dyrk+++ organoids had both a reduced percentage of EdU-positive cells and reduced proliferation compared with wild-type organoids. This study provides evidence for an essential role of DYRK1A as balanced regulator of S-phase entry in HPCs. An exact gene dosage is crucial, as both DYRK1A deficiency and overexpression affect HPC cell cycle progression.

  17. Heterochromatin protein 1 gamma and IκB kinase alpha interdependence during tumour necrosis factor gene transcription elongation in activated macrophages.

    Science.gov (United States)

    Thorne, James L; Ouboussad, Lylia; Lefevre, Pascal F

    2012-09-01

    IκB kinase α (IKKα) is part of the cytoplasmic IKK complex regulating nuclear factor-κB (NF-κB) release and translocation into the nucleus in response to pro-inflammatory signals. IKKα can also be recruited directly to the promoter of NF-κB-dependent genes by NF-κB where it phosphorylates histone H3 at serine 10, triggering recruitment of the bromodomain-containing protein 4 and the positive transcription elongation factor b. Herein, we report that IKKα travels with the elongating form of ribonucleic acid polymerase II together with heterochromatin protein 1 gamma (HP1γ) at NF-κB-dependent genes in activated macrophages. IKKα binds to and phosphorylates HP1γ, which in turn controls IKKα binding to chromatin and phosphorylation of the histone variant H3.3 at serine 31 within transcribing regions. Downstream of transcription end sites, IKKα accumulates with its inhibitor the CUE-domain containing protein 2, suggesting a link between IKKα inactivation and transcription termination.

  18. The Effect of Replacing Fish Meal in the Diet with Enzyme-Treated Soybean Meal (HP310) on Growth and Body Composition of Rainbow Trout Fry.

    Science.gov (United States)

    Haghbayan, Samira; Shamsaie Mehrgan, Mehdi

    2015-11-26

    The potential of enzyme-treated soybean meal powder (HP310) as fish meal alternative in diets for rainbow trout weighing 1.17 ± 0.3 g was evaluated for 60 days. Fish meal was replaced with HP310 at 25%, 50%, 75% and 100% of experimental diets. A control group was also considered. The results showed that diets containing 75% and 100% HP310 had significantly higher feed conversion ratio and lower feed intake, weight gain and specific growth rate compared to fish feed diets containing higher levels of fish protein ingredients (p replacement levels of diet (p > 0.05). However increasing in level of HP310 in the diet caused a significant increase of the white blood cells (p replaced by HP310 showed the highest values of ash and moisture content among the diets and showed significantly different levels when compared with the control and other feeding treatments (p < 0.05).

  19. JIL-1 and Su(var)3-7 Interact Genetically and Counteract Each Other's Effect on Position-Effect Variegation in Drosophila

    Science.gov (United States)

    Deng, Huai; Cai, Weili; Wang, Chao; Lerach, Stephanie; Delattre, Marion; Girton, Jack; Johansen, Jørgen; Johansen, Kristen M.

    2010-01-01

    The essential JIL-1 histone H3S10 kinase is a key regulator of chromatin structure that functions to maintain euchromatic domains while counteracting heterochromatization and gene silencing. In the absence of the JIL-1 kinase, two of the major heterochromatin markers H3K9me2 and HP1a spread in tandem to ectopic locations on the chromosome arms. Here we address the role of the third major heterochromatin component, the zinc-finger protein Su(var)3-7. We show that the lethality but not the chromosome morphology defects associated with the null JIL-1 phenotype to a large degree can be rescued by reducing the dose of the Su(var)3-7 gene and that Su(var)3-7 and JIL-1 loss-of-function mutations have an antagonistic and counterbalancing effect on position-effect variegation (PEV). Furthermore, we show that in the absence of JIL-1 kinase activity, Su(var)3-7 gets redistributed and upregulated on the chromosome arms. Reducing the dose of the Su(var)3-7 gene dramatically decreases this redistribution; however, the spreading of H3K9me2 to the chromosome arms was unaffected, strongly indicating that ectopic Su(var)3-9 activity is not a direct cause of lethality. These observations suggest a model where Su(var)3-7 functions as an effector downstream of Su(var)3-9 and H3K9 dimethylation in heterochromatic spreading and gene silencing that is normally counteracted by JIL-1 kinase activity. PMID:20457875

  20. A Positive Regulatory Loop between a Wnt-Regulated Non-coding RNA and ASCL2 Controls Intestinal Stem Cell Fate.

    Science.gov (United States)

    Giakountis, Antonis; Moulos, Panagiotis; Zarkou, Vasiliki; Oikonomou, Christina; Harokopos, Vaggelis; Hatzigeorgiou, Artemis G; Reczko, Martin; Hatzis, Pantelis

    2016-06-21

    The canonical Wnt pathway plays a central role in stem cell maintenance, differentiation, and proliferation in the intestinal epithelium. Constitutive, aberrant activity of the TCF4/β-catenin transcriptional complex is the primary transforming factor in colorectal cancer. We identify a nuclear long non-coding RNA, termed WiNTRLINC1, as a direct target of TCF4/β-catenin in colorectal cancer cells. WiNTRLINC1 positively regulates the expression of its genomic neighbor ASCL2, a transcription factor that controls intestinal stem cell fate. WiNTRLINC1 interacts with TCF4/β-catenin to mediate the juxtaposition of its promoter with the regulatory regions of ASCL2. ASCL2, in turn, regulates WiNTRLINC1 transcriptionally, closing a feedforward regulatory loop that controls stem cell-related gene expression. This regulatory circuitry is highly amplified in colorectal cancer and correlates with increased metastatic potential and decreased patient survival. Our results uncover the interplay between non-coding RNA-mediated regulation and Wnt signaling and point to the diagnostic and therapeutic potential of WiNTRLINC1. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  1. Regulation of positive and negative emotion: Effects of sociocultural context

    Directory of Open Access Journals (Sweden)

    Sara A. Snyder

    2013-07-01

    Full Text Available Previous research has demonstrated that the use of emotion regulation strategies can vary by sociocultural context. In a previous study, we reported changes in the use of two different emotion regulation strategies at an annual alternative cultural event, Burning Man (McRae, Heller, John, & Gross, 2011. In this sociocultural context, as compared to home, participants reported less use of expressive suppression (a strategy generally associated with maladaptive outcomes, and greater use of cognitive reappraisal (a strategy associated with adaptive outcomes. What remained unclear was whether these changes in self-reported emotion regulation strategy use were characterized by changes in the regulation of positive emotion, negative emotion, or both. We addressed this issue in the current study by asking Burning Man participants separate questions about positive and negative emotion. Using multiple datasets, we not only replicated our previous findings, but also found that the decreased use of suppression is primarily driven by reports of decreased suppression of positive emotion at Burning Man. By contrast, the reported increased use of reappraisal is not characterized by differential reappraisal of positive and negative emotion at Burning Man. Moreover, we observed novel individual differences in the magnitude of these effects. The contextual changes in self-reported suppression that we report are strongest for men and younger participants. For those who had previously attended Burning Man, we observed lower levels of self-reported suppression in both sociocultural contexts: Burning Man and home. These findings have implications for understanding the ways in which certain sociocultural contexts may decrease suppression, and possibly minimize its associated maladaptive effects.

  2. 78 FR 48468 - Hewlett Packard Company, Hewlett Packard Enterprise Business Unit, EG HP Storage, Enterprise...

    Science.gov (United States)

    2013-08-08

    ..., Hewlett Packard Enterprise Business Unit, EG HP Storage, Enterprise Storage, Servers and Networking Storage, APP Management, Research and Development Group, Andover, Massachusetts; Notice of Investigation... Enterprise Business Unit, EG HP Storage, Enterprise Storage, Servers and Networking Storage Division, APP...

  3. Discrete conservation of nonnegativity for elliptic problems solved by the hp-FEM

    Czech Academy of Sciences Publication Activity Database

    Šolín, P.; Vejchodský, Tomáš; Araiza, R.

    2007-01-01

    Roč. 76, 1-3 (2007), s. 205-210 ISSN 0378-4754 R&D Projects: GA ČR GP201/04/P021 Institutional research plan: CEZ:AV0Z10190503 Keywords : discrete nonnegativity conservation * discrete Green's function * elliptic problems * hp-FEM * higher-order finite element methods * Poisson equation * numerical experimetns Subject RIV: BA - General Mathematics Impact factor: 0.738, year: 2007

  4. Comparing Hp(3) evaluated from the conversion coefficients from air kerma to personal dose equivalent for eye lens dosimetry calibrated on a new cylindrical PMMA phantom

    Science.gov (United States)

    Esor, J.; Sudchai, W.; Monthonwattana, S.; Pungkun, V.; Intang, A.

    2017-06-01

    Based on a new occupational dose limit recommended by ICRP (2011), the annual dose limit for the lens of the eye for workers should be reduced from 150 mSv/y to 20 mSv/y averaged over 5 consecutive years in which no single year exceeding 50 mSv. This new dose limit directly affects radiologists and cardiologists whose work involves high radiation exposure over 20 mSv/y. Eye lens dosimetry (Hp(3)) has become increasingly important and should be evaluated directly based on dosimeters that are worn closely to the eye. Normally, Hp(3) dose algorithm was carried out by the combination of Hp(0.07) and Hp(10) values while dosimeters were calibrated on slab PMMA phantom. Recently, there were three reports from European Union that have shown the conversion coefficients from air kerma to Hp(3). These conversion coefficients carried out by ORAMED, PTB and CEA Saclay projects were performed by using a new cylindrical head phantom. In this study, various delivered doses were calculated using those three conversion coefficients while nanoDot, small OSL dosimeters, were used for Hp(3) measurement. These calibrations were performed with a standard X-ray generator at Secondary Standard Dosimetry Laboratory (SSDL). Delivered doses (Hp(3)) using those three conversion coefficients were compared with Hp(3) from nanoDot measurements. The results showed that percentage differences between delivered doses evaluated from the conversion coefficient of each project and Hp(3) doses evaluated from the nanoDots were found to be not exceeding -11.48 %, -8.85 % and -8.85 % for ORAMED, PTB and CEA Saclay project, respectively.

  5. Stimulus-dependent regulation of the phagocyte NADPH oxidase by a VAV1, Rac1, and PAK1 signaling axis

    DEFF Research Database (Denmark)

    Roepstorff, Kirstine; Rasmussen, Izabela Zorawska; Sawada, Makoto

    2008-01-01

    dominant-positive mutants enhanced, whereas dominant-negative mutants inhibited, NADPH oxidase-mediated superoxide generation following formyl-methionyl-leucylphenylalanine or phorbol 12-myristate 13-acetate stimulation. Both Rac1 and the GTP exchange factor VAV1 were required as upstream signaling......The p21-activated kinase-1 (PAK1) is best known for its role in the regulation of cytoskeletal and transcriptional signaling pathways. We show here in the microglia cell line Ra2 that PAK1 regulates NADPH oxidase (NOX-2) activity in a stimulus-specific manner. Thus, conditional expression of PAK1...... proteins in the formyl-methionyl-leucyl-phenylalanine-induced activation of endogenous PAK1. In contrast, PAK1 mutants had no effect on superoxide generation downstream of FcgammaR signaling during phagocytosis of IgG-immune complexes. We further present evidence that the effect of PAK1 on the respiratory...

  6. A new tomato NAC (NAM/ATAF1/2/CUC2) transcription factor, SlNAC4, functions as a positive regulator of fruit ripening and carotenoid accumulation.

    Science.gov (United States)

    Zhu, Mingku; Chen, Guoping; Zhou, Shuang; Tu, Yun; Wang, Yi; Dong, Tingting; Hu, Zongli

    2014-01-01

    Fruit ripening in tomato (Solanum lycopersicum) is a complicated development process affected by both endogenous hormonal and genetic regulators and external signals. Although the role of NOR, a member of the NAC domain family, in mediating tomato fruit ripening has been established, its underlying molecular mechanisms remain unclear. To explore further the role of NAC transcription factors in fruit ripening, we characterized a new tomato NAC domain protein, named SlNAC4, which shows high accumulation in sepal and at the onset of fruit ripening. Various stress treatments including wounding, NaCl, dehydration and low temperature significantly increased the expression of SlNAC4. Reduced expression of SlNAC4 by RNA interference (RNAi) in tomato resulted in delayed fruit ripening, suppressed Chl breakdown and decreased ethylene synthesis mediated mainly through reduced expression of ethylene biosynthesis genes of system-2, and reduced carotenoids by alteration of the carotenoid pathway flux. Transgenic tomato fruits also displayed significant down-regulation of multiple ripening-associated genes, indicating that SlNAC4 functions as a positive regulator of fruit ripening by affecting ethylene synthesis and carotenoid accumulation. Moreover, we also noted that SlNAC4 could not be induced by ethylene and may function upstream of the ripening regulator RIN and positively regulate its expression. Yeast two-hybrid assay further revealed that SlNAC4 could interact with both RIN and NOR protein. These results suggested that ethylene-dependent and -independent processes are regulated by SlNAC4 in the fruit ripening regulatory network.

  7. The PAM-1 aminopeptidase regulates centrosome positioning to ensure anterior-posterior axis specification in one-cell C. elegans embryos.

    Science.gov (United States)

    Fortin, Samantha M; Marshall, Sara L; Jaeger, Eva C; Greene, Pauline E; Brady, Lauren K; Isaac, R Elwyn; Schrandt, Jennifer C; Brooks, Darren R; Lyczak, Rebecca

    2010-08-15

    In the one-cell Caenorhabditis elegans embryo, the anterior-posterior (A-P) axis is established when the sperm donated centrosome contacts the posterior cortex. While this contact appears to be essential for axis polarization, little is known about the mechanisms governing centrosome positioning during this process. pam-1 encodes a puromycin sensitive aminopeptidase that regulates centrosome positioning in the early embryo. Previously we showed that pam-1 mutants fail to polarize the A-P axis. Here we show that PAM-1 can be found in mature sperm and in cytoplasm throughout early embryogenesis where it concentrates around mitotic centrosomes and chromosomes. We provide further evidence that PAM-1 acts early in the polarization process by showing that PAR-1 and PAR-6 do not localize appropriately in pam-1 mutants. Additionally, we tested the hypothesis that PAM-1's role in polarity establishment is to ensure centrosome contact with the posterior cortex. We inactivated the microtubule motor dynein, DHC-1, in pam-1 mutants, in an attempt to prevent centrosome movement from the cortex and restore anterior-posterior polarity. When this was done, the aberrant centrosome movements of pam-1 mutants were not observed and anterior-posterior polarity was properly established, with proper localization of cortical and cytoplasmic determinants. We conclude that PAM-1's role in axis polarization is to prevent premature movement of the centrosome from the posterior cortex, ensuring proper axis establishment in the embryo. Copyright 2010 Elsevier Inc. All rights reserved.

  8. Effect of hypoproteinemia (HP) upon FT4 and FT3 by kinetic radioligandassay (RLA)

    International Nuclear Information System (INIS)

    Bottger, I.G.; Schneck, H.J.

    1985-01-01

    HP, especially hypoalbuminemia (HA), has been associated with false low FT4 by RLA, predominantly of the analogue tracer type. Based upon previous more favourable findings in severe nonthyroidal illness (NTI), this study was designed to study this problem in more detail. Two groups of patients with severe NTI (polytrauma) were selected on the basis of their total serum protein (TSP) concentration and studied during intensive-care. Group I: N = 25, TSP 5.9 g/dl (6.0 - 7.7), A/G: 1.5, sera: N = 76. I and II: low-dose heparin (i.v. 5000 U/24 h), non-detectable in the periphery. The RLA kits used were: FT4/T4 and FT3/T3 (kinetic two-tube), and TBG, Corning Medical, rT3, Serono, TSH, Henning-Berlin, TSP/electrophoresis standard technique. The findings indicate: 1. Typical findings for follow-up of severe NTI; 2. No detection of a significant effect of HP/HA upon these RLAs for FT4 and FT3; and 3. The inter-group differences are most likely due to more severe NT1 in I (R/sub x/, A/G, rT3)

  9. β-TrCP1 Is a Vacillatory Regulator of Wnt Signaling.

    Science.gov (United States)

    Long, Marcus John; Lin, Hong-Yu; Parvez, Saba; Zhao, Yi; Poganik, Jesse Richard; Huang, Paul; Aye, Yimon

    2017-08-17

    Simultaneous hyperactivation of Wnt and antioxidant response (AR) are often observed during oncogenesis. However, it remains unclear how the β-catenin-driven Wnt and the Nrf2-driven AR mutually regulate each other. The situation is compounded because many players in these two pathways are redox sensors, rendering bolus redox signal-dosing methods uninformative. Herein we examine the ramifications of single-protein target-specific AR upregulation in various knockdown lines. Our data document that Nrf2/AR strongly inhibits β-catenin/Wnt. The magnitude and mechanism of this negative regulation are dependent on the direct interaction between β-catenin N terminus and β-TrCP1 (an antagonist of both Nrf2 and β-catenin), and independent of binding between Nrf2 and β-TrCP1. Intriguingly, β-catenin positively regulates AR. Because AR is a negative regulator of Wnt regardless of β-catenin N terminus, this switch of function is likely sufficient to establish a new Wnt/AR equilibrium during tumorigenesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Feedback control of plasma position in the HL-1 tokamak

    International Nuclear Information System (INIS)

    Yuan Baoshan; Jiao Boliang; Yang Kailing

    1991-01-01

    In the HL-1 tokamak with a thick copper shell, the control of plasma position is successfully performed by a feedback-feedforward system with dual mode regulator and the equilibrium field coils outside the shell. The plasma position can be controlled within ±2 mm in both vertical and horizontal directions under the condition that the iron core of transformer is not saturated

  11. A Flexible Binding Site Architecture Provides New Insights into CcpA Global Regulation in Gram-Positive Bacteria.

    Science.gov (United States)

    Yang, Yunpeng; Zhang, Lu; Huang, He; Yang, Chen; Yang, Sheng; Gu, Yang; Jiang, Weihong

    2017-01-24

    Catabolite control protein A (CcpA) is the master regulator in Gram-positive bacteria that mediates carbon catabolite repression (CCR) and carbon catabolite activation (CCA), two fundamental regulatory mechanisms that enable competitive advantages in carbon catabolism. It is generally regarded that CcpA exerts its regulatory role by binding to a typical 14- to 16-nucleotide (nt) consensus site that is called a catabolite response element (cre) within the target regions. However, here we report a previously unknown noncanonical flexible architecture of the CcpA-binding site in solventogenic clostridia, providing new mechanistic insights into catabolite regulation. This novel CcpA-binding site, named cre var , has a unique architecture that consists of two inverted repeats and an intervening spacer, all of which are variable in nucleotide composition and length, except for a 6-bp core palindromic sequence (TGTAAA/TTTACA). It was found that the length of the intervening spacer of cre var can affect CcpA binding affinity, and moreover, the core palindromic sequence of cre var is the key structure for regulation. Such a variable architecture of cre var shows potential importance for CcpA's diverse and fine regulation. A total of 103 potential cre var sites were discovered in solventogenic Clostridium acetobutylicum, of which 42 sites were picked out for electrophoretic mobility shift assays (EMSAs), and 30 sites were confirmed to be bound by CcpA. These 30 cre var sites are associated with 27 genes involved in many important pathways. Also of significance, the cre var sites are found to be widespread and function in a great number of taxonomically different Gram-positive bacteria, including pathogens, suggesting their global role in Gram-positive bacteria. In Gram-positive bacteria, the global regulator CcpA controls a large number of important physiological and metabolic processes. Although a typical consensus CcpA-binding site, cre, has been identified, it remains

  12. AIB1 regulates the ovarian cancer cell cycle through TUG1.

    Science.gov (United States)

    Li, L; Gan, Z-H; Qin, L; Jiao, S-H; Shi, Y

    2017-12-01

    To explore the mechanism of amplified in breast cancer 1 (AIB1) to promote ovarian cancer progress. Cor correlation analysis was performed to obtain the top 100 lncRNAs that were positively correlated with AIB1. The relationship of taurine upregulated gene 1 (TUG1) and clinicopathological characteristics. Moreover, Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) were performed to predict the biological process where TUG1 may be involved in. At last, Cell Counting Kit-8 (CCK-8), colon formation and flow cytometry were conducted to explore the biological process that TUG1 may influence. Meanwhile, Western blot was performed to explore the mechanism of TUG1. In this study, it was found that P73 antisense RNA 1T (TP73-AS1), LINC00654 and TUG1 had the tumor-promoting effect in the top 100 lncRNAs that were positively correlated with AIB1. The expression level of TUG1 was significantly decreased after intervention of AIB1. Then, the clinical data were analyzed and the results showed that TUG1 was related to the tumor residue, tumor staging, tumor grade and lymph node metastasis. Moreover, the bioinformatics analysis revealed that TUG1 was mainly involved in the regulation of cell cycle. After intervention in TUG1, it was found that the cell proliferation capacity was significantly decreased, and the cell cycle was arrested in G1 phase. Finally, Western blot revealed that the expressions of G1 phase-related proteins were significantly changed. This study indicated that AIB1 regulates the cycle of ovarian cancer cells through TUG1. This study proved that AIB1 can regulate the cell cycle through regulating TUG1.

  13. PENINGKATAN CD8 DAN IFN-γ PADA HYPERSENSITIVITY PNEUMONITIS (HP AKIBAT PAJANAN DEBU PENGGILINGAN PADI

    Directory of Open Access Journals (Sweden)

    Isa Ma'rufi

    2017-10-01

    Full Text Available Abstrak     Masalah klinis kesehatan kerja pada pekerja penggilingan padi saat ini adalah penyakit saluran pernafasan. Penelitian ini bertujuan untuk menganalisis peningkatan CD8 dan IFN-γ pada Pneumonitis Hipersensitif (HP akibat pajanan debu penggilingan padi pada mencit  (Musmusculus BALB/C. Penelitian yang dilakukan adalah penelitian eksperimental laboratoris dengan hewan coba mencit (Musmusculus BALB/C,  rancangan penelitian yang digunakan adalah Randomized the post test only control group design. Mencit  (Musmusculus BALB/C dipajan dengan debu penggilingan padi selama empat jam/hari selama tiga puluh hari dengan konsentrasi 0.50 mg/m3, 0.75 mg/m3, 1.00 mg/m3. Variabel bebas adalah debu penggilingan padi, sedangkan variabel tergantung adalah   CD8 dan IFN-γ, serta gambaran histopatologis paru mencit, sedangkan variabel kendali adalah strain, berat badan, dan umur. Hasil penelitian menunjukkan bahwa terjadi peningkatan kadar CD8 antara kontrol dengan perlakuan, dan secara statistik  ada perbedaan yang bermakna. Kemudian terjadi peningkatan IFN-γ dan secara statistik ada perbedaan yang bermakna antara kontrol dan perlakuan pada mencit  (Musmusculus BALB/C. Hasil penelitian dapat digunakan sebagai dasar upaya pencegahan dan pemberian terapi penyakit HP lebih dini sehingga dapat meningkatkan kualitas paru.   Kata Kunci: CD8, IFN-γ,  debu penggilingan padi     Abtract   The purpose of this research was to analyze increase of CD8  and IFN-γ of Hypersensitivity Pneumonitis (HP as a result from the exposure of dust from paddy milling on mice (MusmusculusBALB/C. The research done was a laboratory experimental research with mice (MusMusculus as experimental animal.  The research design used was the post only control group design using mice (MusMusculus Balb/c as experimental animal.  Mice (Musmusculus Balb/c were exposed to dust from paddy milling for four (4 hours/day and it was done for thirty (30 days with the exposed

  14. Present problems with atomic energy laws and regulations. 2. ed.

    International Nuclear Information System (INIS)

    Bluemel, W.

    1993-01-01

    The report includes two speeches held by the author on the 3rd Japanese-German Atomic Law Symposion in Tokio on 5-7 Oct. 1992. The titles are: 1) Recent developments in the German Laws and regulations ruling atomic energy; 2) Legal aspects of stopping and eliminating nuclear plants in Germany. Both speeches were translated into Japanese. (HP) [de

  15. Simulation and thermoeconomic analysis of different configurations of gas turbine (GT)-based dual-purpose power and desalination plants (DPPDP) and hybrid plants (HP)

    International Nuclear Information System (INIS)

    Rensonnet, Thibaut; Uche, Javier; Serra, Luis

    2007-01-01

    This paper contains a simulation and a thermoeconomic analysis of several configurations of gas turbine (GT)-based dual-purpose power and desalination plants (DPPDP): Gas turbine with reverse osmosis (GT+RO), combined cycle with reverse osmosis (CC+RO), combined cycle with multi-effect distillation (CC+MED) and two different hybrid plant (HP) arrangements combining CC, MED and RO (CC+MED+RO, CC+MED+RO bis ). The last two configurations only differ from the feed solution to the MED units (raw seawater or brine coming from the RO discharge). A complete thermodynamic simulation at both design and at part load conditions has been made, as well as an exergy and an exergo-economic (thermoeconomic) analysis of each configuration, in order to compare the evolution of the water and electricity cost for different arrangements. The results show that even for a significantly reduced fuel cost (1.42 $/GJ), the CC is much more profitable than a GT operating in open cycle, with electricity cost values of 1.647 and 2.166 c$/kWh, respectively. As was expected, RO is more efficient and profitable than MED desalination processes, the difference in the obtained desalted water cost being significant. In the hybrid configuration with MED fed by the RO brine discharge, a decrease in the equivalent electrical consumption of nearly 2 kWh/m 3 was achieved, but even in this case RO was more efficient (14.15 vs. 4.048 kWh/m 3 ). The evolution of electricity cost in each configuration is more similar at part load operation than at full load, but in the case of water cost, RO is once again more profitable and less sensitive to load variations. Costs given in this paper correspond to investment and fuel costs. Further, profitability and operation strategies of HP, i.e., DPPDP combining distillation and membrane processes, are also analyzed. It is shown that HP can be more profitable than RO plants in the case of increasing the water production capacity of existing DPPDP, because the profit

  16. Negative-tone imaging with EUV exposure for 14nm hp and beyond

    Science.gov (United States)

    Tsubaki, Hideaki; Nihashi, Wataru; Tsuchihashi, Toru; Fujimori, Toru; Momota, Makoto; Goto, Takahiro

    2015-03-01

    Manipulation of dissolution properties by changing organic solvent developer and rinse material provides a novel technology to obtain fine pattern beyond the limitation of imaging system based on alkaline developer. QCM study showed no swelling character in negative-tone imaging (NTI) process even for current developer of n-butyl acetate (nBA). Actually, NTI process has shown advantages on resolution and line-width roughness (LWR) in loose pitch around 30 ~ 45 nm hp as a consequence of its non-swelling character. On the other hand, bridge and collapse limited its resolution below 20 nm hp, indicating that non-negligible amount of swelling still exists for tight pitch resolution. We investigated effects of solubility parameter of organic solvents on resolution below 20 nm hp. A bridge was reduced with a decrease in the solubility parameter dp from nBA. On the other hand, much lower dp caused film remaining due to its extremely slow Rmax. Based on these results, we newly developed FN-DP301 containing organic solvent with smaller dp than nBA. Although rinse solvent gave negligible effects on bridge, there is a clear improvement on pattern collapse only in case of using new rinse solvent of FN-RP311. Lithographic performances of NTI process using nBA and FN-DP301 together with the other organic solvents were described in this paper under exposures with an E-beam and a EUV light. It is emphasized that 14 nm hp resolution was obtained only using FN-DP301 as a developer and FN-RP311 as a rinse under E-beam exposure. NTI showed 43% faster photospeed in comparison with PTI at 16 nm hp, indicating that NTI is applicable to obtain high throughput with maintaining resolution. In addition, sub-20 nm trench was obtained using NTI without bridge under EUV exposure, all of which are attributed to the low swelling character of NTI process. Similarly, NTI was able to print 20 nm dots using NXE:3100 with only a little peeling. Conversely CH patterning was significantly worse with NTI

  17. Susceptibility of the tomato mutant high pigment-2dg (hp-2dg) to Orobanche spp. infection.

    Science.gov (United States)

    López-Ráez, Juan Antonio; Charnikhova, Tatsiana; Mulder, Patrick; Kohlen, Wouter; Bino, Raoul; Levin, Ilan; Bouwmeester, Harro

    2008-08-13

    The consumption of natural products with potential health benefits has been continuously growing, and enhanced pigmentation is of major economic importance in fruits and vegetables. The tomato hp-2 ( dg ) is an important mutant line that has been introgressed into commercial tomato cultivars marketed as lycopene rich tomatoes (LRT) because of their enhanced fruit pigmentation, attributed to higher levels of carotenoids, including lycopene. Strigolactones are signaling compounds that mediate host finding in root parasitic plants and are biosynthetically derived from carotenoids. Considering the high carotenoid content of the hp-2 ( dg ) mutant, we studied its susceptibility to the root parasite Orobanche. In a field experiment, the average number of Orobanche aegyptiaca plants growing on hp-2 ( dg ) was surprisingly significantly reduced compared with its isogenic wild-type counterpart. In vitro assays and LC-MS/MS analysis showed that this reduction was associated with a lower production of strigolactones, which apparently renders the high-carotenoid hp-2 ( dg ) mutant less susceptible to Orobanche.

  18. An object-oriented decomposition of the adaptive-hp finite element method

    Energy Technology Data Exchange (ETDEWEB)

    Wiley, J.C.

    1994-12-13

    Adaptive-hp methods are those which use a refinement control strategy driven by a local error estimate to locally modify the element size, h, and polynomial order, p. The result is an unstructured mesh in which each node may be associated with a different polynomial order and which generally require complex data structures to implement. Object-oriented design strategies and languages which support them, e.g., C++, help control the complexity of these methods. Here an overview of the major classes and class structure of an adaptive-hp finite element code is described. The essential finite element structure is described in terms of four areas of computation each with its own dynamic characteristics. Implications of converting the code for a distributed-memory parallel environment are also discussed.

  19. Lactobacillus fermentum HP3–Mediated Fermented Hericium erinaceus Juice as a Health Promoting Food Supplement to Manage Diabetes Mellitus

    Science.gov (United States)

    Chaiyasut, Chaiyavat; Woraharn, Sasimar; Sivamaruthi, Bhagavathi Sundaram; Lailerd, Narissara; Kesika, Periyanaina; Peerajan, Sartjin

    2018-01-01

    The current study investigated the antidiabetic property of Lactobacillus fermentum HP3–mediated fermented Hericium erinaceus juice (FHJ) using male Wistar rats with streptozotocin-induced diabetes mellitus (DM). FHJ was prepared using boiled mushroom juice and L. fermentum HP3. Amino acid and γ-aminobutyric acid (GABA) content of FHJ was analyzed. Streptozotocin-induced DM rats were supplemented with FHJ in a pre- and posttreatment method. The changes in plasma insulin, plasma glucose level, glycated hemoglobin (HbA1c), representative cytokines, and the antioxidant system were assessed in experimental rats using spectrophotometric methods and enzyme-linked immunosorbent assay. The supplementation of FHJ improved the body mass, insulin level, and recovery progress of hyperglycemia. HbA1c level was altered by the FHJ intervention. The inflammatory cytokines level was suppressed in FHJ supplemented group compared with control. Intervention of FHJ and insulin improved the production of interleukin-10 and transforming growth factor-–β1 in DM rat. The study suggested that fermented H erinaceus juice may be used as one of the food-based health-promoting supplement to manage DM along with medication. PMID:29619846

  20. DMPD: When signaling pathways collide: positive and negative regulation of toll-likereceptor signal transduction. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18631453 When signaling pathways collide: positive and negative regulation of toll-...uction. PubmedID 18631453 Title When signaling pathways collide: positive and neg...l) Show When signaling pathways collide: positive and negative regulation of toll-likereceptor signal transd...likereceptor signal transduction. O'Neill LA. Immunity. 2008 Jul 18;29(1):12-20. (.png) (.svg) (.html) (.csm

  1. Agp2, a Member of the Yeast Amino Acid Permease Family, Positively Regulates Polyamine Transport at the Transcriptional Level

    KAUST Repository

    Aouida, Mustapha

    2013-06-03

    Agp2 is a plasma membrane protein of the Saccharomyces cerevisiae amino acid transporter family, involved in high-affinity uptake of various substrates including L-carnitine and polyamines. The discovery of two high affinity polyamine permeases, Dur3 and Sam3, prompted us to investigate whether Agp2 directly transports polyamines or acts instead as a regulator. Herein, we show that neither dur3? nor sam3? single mutant is defective in polyamine transport, while the dur3? sam3? double mutant exhibits a sharp decrease in polyamine uptake and an increased resistance to polyamine toxicity similar to the agp2? mutant. Studies of Agp2 localization indicate that in the double mutant dur3? sam3?, Agp2-GFP remains plasma membrane-localized, even though transport of polyamines is strongly reduced. We further demonstrate that Agp2 controls the expression of several transporter genes including DUR3 and SAM3, the carnitine transporter HNM1 and several hexose, nucleoside and vitamin permease genes, in addition to SKY1 encoding a SR kinase that positively regulates low-affinity polyamine uptake. Furthermore, gene expression analysis clearly suggests that Agp2 is a strong positive regulator of additional biological processes. Collectively, our data suggest that Agp2 might respond to environmental cues and thus regulate the expression of several genes including those involved in polyamine transport. © 2013 Aouida et al.

  2. Agp2, a Member of the Yeast Amino Acid Permease Family, Positively Regulates Polyamine Transport at the Transcriptional Level

    KAUST Repository

    Aouida, Mustapha; Texeira, Marta Rubio; Thevelein, Johan M.; Poulin, Richard; Ramotar, Dindial

    2013-01-01

    Agp2 is a plasma membrane protein of the Saccharomyces cerevisiae amino acid transporter family, involved in high-affinity uptake of various substrates including L-carnitine and polyamines. The discovery of two high affinity polyamine permeases, Dur3 and Sam3, prompted us to investigate whether Agp2 directly transports polyamines or acts instead as a regulator. Herein, we show that neither dur3? nor sam3? single mutant is defective in polyamine transport, while the dur3? sam3? double mutant exhibits a sharp decrease in polyamine uptake and an increased resistance to polyamine toxicity similar to the agp2? mutant. Studies of Agp2 localization indicate that in the double mutant dur3? sam3?, Agp2-GFP remains plasma membrane-localized, even though transport of polyamines is strongly reduced. We further demonstrate that Agp2 controls the expression of several transporter genes including DUR3 and SAM3, the carnitine transporter HNM1 and several hexose, nucleoside and vitamin permease genes, in addition to SKY1 encoding a SR kinase that positively regulates low-affinity polyamine uptake. Furthermore, gene expression analysis clearly suggests that Agp2 is a strong positive regulator of additional biological processes. Collectively, our data suggest that Agp2 might respond to environmental cues and thus regulate the expression of several genes including those involved in polyamine transport. © 2013 Aouida et al.

  3. In Sync and in Control: A Meta-Analysis of Parent-Child Positive Behavioral Synchrony and Youth Self-Regulation.

    Science.gov (United States)

    Davis, Molly; Bilms, Joanie; Suveg, Cynthia

    2017-12-01

    A growing body of research has highlighted the connection between parent-child positive behavioral synchrony and youth self-regulation; however, this association has yet to be the focus of a meta-analytic review. Therefore, the present meta-analysis aimed to estimate the magnitude of the relation between parent-child positive behavioral synchrony and youth self-regulation and to identify moderator variables that can explain the variability in the degree of this association across the extant literature. A thorough literature search of two major databases, in addition to scanning the reference sections of relevant articles, yielded a total of 10 peer-reviewed articles (24 effect sizes, 658 children) that were eligible for inclusion in the current meta-analysis. Results from the overall mean effect size calculation using a random-effects model indicated that parent-child positive behavioral synchrony was significantly, positively correlated with youth self-regulation and the effect size was medium. Children's ages at the time of synchrony and self-regulation measurements, as well as parent gender, served as significant moderator variables. Findings from the present meta-analysis can help to refine existing theoretical models on the role of the parent-child relationship in youth adjustment. Prevention and intervention efforts may benefit from an increased emphasis on building parent-child positive behavioral synchrony to promote youth self-regulation and thus children's overall well-being. © 2016 Family Process Institute.

  4. c-Fos downregulation positively regulates EphA5 expression in a congenital hypothyroidism rat model.

    Science.gov (United States)

    Song, Honghua; Zheng, Yuqin; Cai, Fuying; Ma, Yanyan; Yang, Jingyue; Wu, Youjia

    2018-04-01

    The EphA5 receptor is well established as an axon guidance molecule during neural system development and plays an important role in dendritic spine formation and synaptogenesis. Our previous study has showed that EphA5 is decreased in the developing brain of congenital hypothyroidism (CH) and the EphA5 promoter methylation modification participates in its decrease. c-Fos, a well-kown transcription factor, has been considered in association with brain development. Bioinformatics analysis showed that the EphA5 promoter region contained five putative c-fos binding sites. The chromatin immunoprecipitation (ChIP) assays were used to assess the direct binding of c-fos to the EphA5 promoter. Furthermore, dual-luciferase assays showed that these three c-fos protein binding sites were positive regulatory elements for EphA5 expression in PC12 cells. Moreover, We verified c-fos positively regulation for EphA5 expression in CH model. Q-PCR and Western blot showed that c-fos overexpression could upregulate EphA5 expression in hippocampal neurons of rats with CH. Our results suggest that c-fos positively regulates EphA5 expression in CH rat model.

  5. The APSES protein Sok2 is a positive regulator of sporulation in Ashbya gossypii.

    Science.gov (United States)

    Wasserstrom, Lisa; Dünkler, Alexander; Walther, Andrea; Wendland, Jürgen

    2017-12-01

    Ashbya gossypii is a homothallic, flavinogenic, filamentous ascomycete that starts overproduction of riboflavin and fragments its mycelium quantitatively into spore producing sporangia at the end of a growth phase. Mating is not required for sporulation and the standard homothallic laboratory strain is a MATa strain. Here we show that ectopic expression of Saccharomyces cerevisiae MATα2 in A. gossypii completely suppresses sporulation, inhibits riboflavin overproduction and downregulates among others AgSOK2. AgSok2 belongs to a fungal-specific group of (APSES) transcription factors. Deletion of AgSOK2 strongly reduces riboflavin production and blocks sporulation. The initiator of meiosis, AgIME1, is a transcription factor essential for sporulation. We characterized the AgIME1 promoter region required for complementation of the Agime1 mutant. Reporter assays with AgIME1 promoter fragments fused to lacZ showed that AgSok2 does not control AgIME1 transcription. However, global transcriptome analysis identified two other essential regulators of sporulation, AgIME2 and AgNDT80, as potential targets of AgSok2. Our data suggest that sporulation and riboflavin production in A. gossypii are under mating type locus and nutritional control. Sok2, a target of the cAMP/protein kinase A pathway, serves as a central positive regulator to promote sporulation. This contrasts Saccharomyces cerevisiae where Sok2 is a repressor of IME1 transcription. © 2017 John Wiley & Sons Ltd.

  6. A Molecular Mechanism to Regulate Lysosome Motility for Lysosome Positioning and Tubulation

    Science.gov (United States)

    Li, Xinran; Rydzewski, Nicholas; Hider, Ahmad; Zhang, Xiaoli; Yang, Junsheng; Wang, Wuyang; Gao, Qiong; Cheng, Xiping; Xu, Haoxing

    2016-01-01

    To mediate the degradation of bio-macromolecules, lysosomes must traffic towards cargo-carrying vesicles for subsequent membrane fusion or fission. Mutations of the lysosomal Ca2+ channel TRPML1 cause lysosome storage disease (LSD) characterized by disordered lysosomal membrane trafficking in cells. Here we show that TRPML1 activity is required to promote Ca2+-dependent centripetal movement of lysosomes towards the perinuclear region, where autophagosomes accumulate, upon autophagy induction. ALG-2, an EF-hand-containing protein, serves as a lysosomal Ca2+ sensor that associates physically with the minus-end directed dynactin-dynein motor, while PI(3,5)P2, a lysosome-localized phosphoinositide, acts upstream of TRPML1. Furthermore, the PI(3,5)P2-TRPML1-ALG-2-dynein signaling is necessary for lysosome tubulation and reformation. In contrast, the TRPML1 pathway is not required for the perinuclear accumulation of lysosomes observed in many LSDs, which is instead likely caused by secondary cholesterol accumulation that constitutively activates Rab7-RILP-dependent retrograde transport. Collectively, Ca2+ release from lysosomes provides an on-demand mechanism regulating lysosome motility, positioning, and tubulation. PMID:26950892

  7. Monte Carlo determination of the conversion coefficients Hp(3)/Ka in a right cylinder phantom with 'PENELOPE' code. Comparison with 'MCNP' simulations.

    Science.gov (United States)

    Daures, J; Gouriou, J; Bordy, J M

    2011-03-01

    This work has been performed within the frame of the European Union ORAMED project (Optimisation of RAdiation protection for MEDical staff). The main goal of the project is to improve standards of protection for medical staff for procedures resulting in potentially high exposures and to develop methodologies for better assessing and for reducing, exposures to medical staff. The Work Package WP2 is involved in the development of practical eye-lens dosimetry in interventional radiology. This study is complementary of the part of the ENEA report concerning the calculations with the MCNP-4C code of the conversion factors related to the operational quantity H(p)(3). In this study, a set of energy- and angular-dependent conversion coefficients (H(p)(3)/K(a)), in the newly proposed square cylindrical phantom made of ICRU tissue, have been calculated with the Monte-Carlo code PENELOPE and MCNP5. The H(p)(3) values have been determined in terms of absorbed dose, according to the definition of this quantity, and also with the kerma approximation as formerly reported in ICRU reports. At a low-photon energy (up to 1 MeV), the two results obtained with the two methods are consistent. Nevertheless, large differences are showed at a higher energy. This is mainly due to the lack of electronic equilibrium, especially for small angle incidences. The values of the conversion coefficients obtained with the MCNP-4C code published by ENEA quite agree with the kerma approximation calculations obtained with PENELOPE. We also performed the same calculations with the code MCNP5 with two types of tallies: F6 for kerma approximation and *F8 for estimating the absorbed dose that is, as known, due to secondary electrons. PENELOPE and MCNP5 results agree for the kerma approximation and for the absorbed dose calculation of H(p)(3) and prove that, for photon energies larger than 1 MeV, the transport of the secondary electrons has to be taken into account.

  8. Development of a safety and regulation systems simulation program II

    International Nuclear Information System (INIS)

    1985-05-01

    This report describes the development of a safety and regulation systems simulation program under contract to the Atomic Energy Control Board of Canada. A systems logic interaction simulation (SLISIM) program was developed for the AECB's HP-1000 computer which operates in the interactive simulation (INSIM) program environment. The SLISIM program simulates the spatial neutron dynamics, the regulation of the reactor power and in this version the CANDU-PHW 600 MW(e) computerized shutdown systems' trip parameters. The modular concept and interactive capability of the INSIM environment provides the user with considerable flexibility of the setup and control of the simulation

  9. Determination of effective dose in anisotropic gamma radiation fields: application of dosimeters calibrated in terms of Hp(10)

    International Nuclear Information System (INIS)

    Chumak, V. V.; Bakhanova, E. V.

    2003-01-01

    In this presentation authors deals with determination of effective dose in anisotropic gamma radiation fields. It was conclude that: - Straightforward application of Hp(10) as surrogate for E may not work under certain conditions; - Partial data on behavior of E and Hp(10) for different dosimeters allow to estimate E/Hp(10) conversion coefficients for any particular composite source; - In practical situations, anisotropy of workplace fields may be measured by six- collimator device assessing contribution to a dose from six orthogonal directions; - Reasonably conservative conversion coefficients may be assessed for given energy spectrum and degree of anisotropy of workplace fields; - For strongly anisotropic fields multiple dosimetry approach gives the best estimate of E comparing to plain Hp(10) readouts or integral conversion coefficients

  10. Shikonin regulates C-MYC and GLUT1 expression through the MST1-YAP1-TEAD1 axis

    Energy Technology Data Exchange (ETDEWEB)

    Vališ, Karel, E-mail: karel.valis@biomed.cas.cz [Laboratory of Structural Biology and Cell Signaling, Institute of Microbiology, v.v.i., The Czech Academy of Sciences, Prague (Czech Republic); Faculty of Science, Charles University, Prague (Czech Republic); Talacko, Pavel; Grobárová, Valéria [Laboratory of Structural Biology and Cell Signaling, Institute of Microbiology, v.v.i., The Czech Academy of Sciences, Prague (Czech Republic); Faculty of Science, Charles University, Prague (Czech Republic); Černý, Jan [Faculty of Science, Charles University, Prague (Czech Republic); Novák, Petr, E-mail: pnovak@biomed.cas.cz [Laboratory of Structural Biology and Cell Signaling, Institute of Microbiology, v.v.i., The Czech Academy of Sciences, Prague (Czech Republic); Faculty of Science, Charles University, Prague (Czech Republic)

    2016-12-10

    The general mechanism underlying the tumor suppressor activity of the Hippo signaling pathway remains unclear. In this study, we explore the molecular mechanisms connecting the Hippo signaling pathway with glucose metabolism. We have found that two key regulators of glycolysis, C-MYC and GLUT1, are targets of the Hippo signaling pathway in human leukemia cells. Our results revealed that activation of MST1 by the natural compound shikonin inhibited the expression of GLUT1 and C-MYC. Furthermore, RNAi experiments confirmed the regulation of GLUT1 and C-MYC expression via the MST1-YAP1-TEAD1 axis. Surprisingly, YAP1 was found to positively regulate C-MYC mRNA levels in complex with TEAD1, while it negatively regulates C-MYC levels in cooperation with MST1. Hence, YAP1 serves as a rheostat for C-MYC, which is regulated by MST1. In addition, depletion of MST1 stimulates lactate production, whereas the specific depletion of TEAD1 has an opposite effect. The inhibition of lactate production and cellular proliferation induced by shikonin also depends on the Hippo pathway activity. Finally, a bioinformatic analysis revealed conserved TEAD-binding motifs in the C-MYC and GLUT1 promoters providing another molecular data supporting our observations. In summary, regulation of glucose metabolism could serve as a new tumor suppressor mechanism orchestrated by the Hippo signaling pathway. - Highlights: • Shikonin inhibits C-MYC and GLUT1 expression in MST1 and YAP1 dependent manner. • YAP1-TEAD1 interaction activates C-MYC and GLUT1 expression. • MST1 in cooperation with YAP1 inhibits C-MYC and GLUT1 expression. • MST1-YAP1-TEAD1 axis regulates lactate production by leukemic cells. • MST1 and YAP1 proteins block proliferation of leukemic cells.

  11. Culturable Bacterial Microbiota of the Stomach of Helicobacter pylori Positive and Negative Gastric Disease Patients

    Directory of Open Access Journals (Sweden)

    Yalda Khosravi

    2014-01-01

    Full Text Available Human stomach is the only known natural habitat of Helicobacter pylori (Hp, a major bacterial pathogen that causes different gastroduodenal diseases. Despite this, the impact of Hp on the diversity and the composition of the gastric microbiota has been poorly studied. In this study, we have analyzed the culturable gastric microbiota of 215 Malaysian patients, including 131 Hp positive and 84 Hp negative individuals that were affected by different gastric diseases. Non-Hp bacteria isolated from biopsy samples were identified by matrix assisted laser desorption ionization-time of flight mass spectrometry based biotyping and 16SrRNA sequencing. The presence of Hp did not significantly modify the diversity of the gastric microbiota. However, correlation was observed between the isolation of Streptococci and peptic ulcer disease. In addition, as a first report, Burkholderia pseudomallei was also isolated from the gastric samples of the local population. This study suggested that there may be geographical variations in the diversity of the human gastric microbiome. Geographically linked diversity in the gastric microbiome and possible interactions between Hp and other bacterial species from stomach microbiota in pathogenesis are proposed for further investigations.

  12. Capsicum annuum transcription factor WRKYa positively regulates defense response upon TMV infection and is a substrate of CaMK1 and CaMK2.

    Science.gov (United States)

    Huh, Sung Un; Lee, Gil-Je; Jung, Ji Hoon; Kim, Yunsik; Kim, Young Jin; Paek, Kyung-Hee

    2015-01-23

    Plants are constantly exposed to pathogens and environmental stresses. To minimize damage caused by these potentially harmful factors, plants respond by massive transcriptional reprogramming of various stress-related genes via major transcription factor families. One of the transcription factor families, WRKY, plays an important role in diverse stress response of plants and is often useful to generate genetically engineered crop plants. In this study, we carried out functional characterization of CaWRKYa encoding group I WRKY member, which is induced during hypersensitive response (HR) in hot pepper (Capsicum annuum) upon Tobacco mosaic virus (TMV) infection. CaWRKYa was involved in L-mediated resistance via transcriptional reprogramming of pathogenesis-related (PR) gene expression and affected HR upon TMV-P0 infection. CaWRKYa acts as a positive regulator of this defense system and could bind to the W-box of diverse PR genes promoters. Furthermore, we found Capsicum annuum mitogen-activated protein kinase 1 (CaMK1) and 2 (CaMK2) interacted with CaWRKYa and phosphorylated the SP clusters but not the MAPK docking (D)-domain of CaWRKYa. Thus, these results demonstrated that CaWRKYa was regulated by CaMK1 and CaMK2 at the posttranslational level in hot pepper.

  13. A point kernel shielding code, PKN-HP, for high energy proton incident

    Energy Technology Data Exchange (ETDEWEB)

    Kotegawa, Hiroshi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1996-06-01

    A point kernel integral technique code PKN-HP, and the related thick target neutron yield data have been developed to calculate neutron and secondary gamma-ray dose equivalents in ordinary concrete and iron shields for fully stopping length C, Cu and U-238 target neutrons produced by 100 MeV-10 GeV proton incident in a 3-dimensional geometry. The comparisons among calculation results of the present code and other calculation techniques, and measured values showed the usefulness of the code. (author)

  14. Application of a Long Term Asset Management Strategy for HP Feedwater Heaters

    International Nuclear Information System (INIS)

    Won, Se Youl; Yun, Eun Sub; Park, Young Sheop

    2008-01-01

    As the commercial operating year of nuclear power plants is increased, it becomes imperative to develop integrated cost-effective asset management and to improve plans for degraded Structures, Systems, and Components (SSCs) in terms of safety and economical consideration. A long-term asset management (LTAM) strategy can improve the condition of nuclear plants, maximize their value, and optimize their operational life by maintaining their safety. This paper presents an optimized LTAM plan for HP feedwater heaters at a specific nuclear power plant

  15. Nonconforming h-p spectral element methods for elliptic problems

    Indian Academy of Sciences (India)

    In [6,7,13,14] h-p spectral element methods for solving elliptic boundary value problems on polygonal ... Let M denote the number of corner layers and W denote the number of degrees of .... β is given by Theorem 2.2 of [3] which can be stated.

  16. PGC1α −1 Nucleosome Position and Splice Variant Expression and Cardiovascular Disease Risk in Overweight and Obese Individuals

    Directory of Open Access Journals (Sweden)

    Tara M. Henagan

    2014-01-01

    Full Text Available PGC1α, a transcriptional coactivator, interacts with PPARs and others to regulate skeletal muscle metabolism. PGC1α undergoes splicing to produce several mRNA variants, with the NTPGC1α variant having a similar biological function to the full length PGC1α (FLPGC1α. CVD is associated with obesity and T2D and a lower percentage of type 1 oxidative fibers and impaired mitochondrial function in skeletal muscle, characteristics determined by PGC1α expression. PGC1α expression is epigenetically regulated in skeletal muscle to determine mitochondrial adaptations, and epigenetic modifications may regulate mRNA splicing. We report in this paper that skeletal muscle PGC1α  −1 nucleosome (−1N position is associated with splice variant NTPGC1α but not FLPGC1α expression. Division of participants based on the −1N position revealed that those individuals with a1N phased further upstream from the transcriptional start site (UP expressed lower levels of NTPGC1α than those with the −1N more proximal to TSS (DN. UP showed an increase in body fat percentage and serum total and LDL cholesterol. These findings suggest that the −1N may be a potential epigenetic regulator of NTPGC1α splice variant expression, and −1N position and NTPGC1α variant expression in skeletal muscle are linked to CVD risk. This trial is registered with clinicaltrials.gov, identifier NCT00458133.

  17. Expression of alkyl hydroperoxide reductase is regulated negatively by OxyR1 and positively by RpoE2 sigma factor in Azospirillum brasilense Sp7.

    Science.gov (United States)

    Singh, Sudhir; Dwivedi, Susheel Kumar; Singh, Vijay Shankar; Tripathi, Anil Kumar

    2016-10-01

    OxyR proteins are LysR-type transcriptional regulators, which play an important role in responding to oxidative stress in bacteria. Azospirillum brasilense Sp7 harbours two copies of OxyR. The inactivation of the oxyR1, the gene organized divergently to ahpC in A. brasilense Sp7, led to an increased tolerance to alkyl hydroperoxides, which was corroborated by an increase in alkyl hydroperoxide reductase (AhpC) activity, enhanced expression of ahpC :lacZ fusion and increased synthesis of AhpC protein in the oxyR1::km mutant. The upstream region of ahpC promoter harboured a putative OxyR binding site, T-N11-A. Mutation of T, A or both in the T-N11-Amotif caused derepression of ahpC in A. brasilense suggesting that T-N11-A might be the binding site for a negative regulator. Retardation of the electrophoretic mobility of the T-N11-A motif harbouring oxyR1-ahpC intergenic DNA by recombinant OxyR1, under reducing as well as oxidizing conditions, indicated that OxyR1 acts as a negative regulator of ahpC in A. brasilense. Sequence of the promoter of ahpC, predicted on the basis of transcriptional start site, and an enhanced expression of ahpC:lacZ fusion in chrR2::km mutant background suggested that ahpC promoter was RpoE2 dependent. Thus, this study shows that in A. brasilense Sp7, ahpC expression is regulated negatively by OxyR1 but is regulated positively by RpoE2, an oxidative-stress-responsive sigma factor. It also shows that OxyR1 regulates the expression RpoE1, which is known to play an important role during photooxidative stress in A. brasilense.

  18. Difficulties in emotion regulation mediate negative and positive affects and craving in alcoholic patients.

    Science.gov (United States)

    Khosravani, Vahid; Sharifi Bastan, Farangis; Ghorbani, Fatemeh; Kamali, Zoleikha

    2017-08-01

    The aim of this study was to assess the mediating effects of difficulties in emotion regulation (DER) on the relations of negative and positive affects to craving in alcoholic patients. 205 treatment-seeking alcoholic outpatients were included. DER, positive and negative affects as well as craving were evaluated by the Difficulties in Emotion Regulation Scale (DERS), the Positive/Negative Affect Scales, and the Obsessive Compulsive Drinking Scale (OCDS) respectively. Clinical factors including depression and severity of alcohol dependence were investigated by the Alcohol Use Disorders Identification Test (AUDIT) and the Beck Depression Inventory-II (BDI-II) respectively. Results revealed that both increased negative affect and decreased positive affect indirectly influenced craving through limited access to emotion regulation strategies. It was concluded that limited access to emotion regulation strategies may be important in predicting craving for alcoholics who experience both increased negative affect and decreased positive affect. This suggests that treatment and prevention efforts focused on increasing positive affect, decreasing negative affect and teaching effective regulation strategies may be critical in reducing craving in alcoholic patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Effect of antiparkinson drug HP-200 (Mucuna pruriens) on the central monoaminergic neurotransmitters.

    Science.gov (United States)

    Manyam, Bala V; Dhanasekaran, Muralikrishnan; Hare, Theodore A

    2004-02-01

    HP-200, which contains Mucuna pruriens endocarp, has been shown to be effective in the treatment of Parkinson's disease. Mucuna pruriens endocarp has also been shown to be more effective compared to synthetic levodopa in an animal model of Parkinson's disease. The present study was designed to elucidate the long-term effect of Mucuna pruriens endocarp in HP-200 on monoaminergic neurotransmitters and its metabolite in various regions of the rat brain. HP-200 at a dose of 2.5, 5.0 or 10.0 g/kg/day was mixed with rat chow and fed daily ad lib to Sprague-Dawley rats (n = 6 for each group) for 52 weeks. Controls (n = 6) received no drug. Random assignment was made for doses and control. The rats were sacrificed at the end of 52 weeks and the neurotransmitters were analyzed in the cortex, hippocampus, substantia nigra and striatum. Oral administration of Mucuna pruriens endocarp in the form of HP-200 had a significant effect on dopamine content in the cortex with no significant effect on levodopa, norepinephrine or dopamine, serotonin, and their metabolites- HVA, DOPAC and 5-HIAA in the nigrostriatal tract. The failure of Mucuna pruriens endocarp to significantly affect dopamine metabolism in the striatonigral tract along with its ability to improve Parkinsonian symptoms in the 6-hydorxydopamine animal model and humans may suggest that its antiparkinson effect may be due to components other than levodopa or that it has an levodopa enhancing effect. Copyright 2004 John Wiley & Sons, Ltd. Copyright 2004 John Wiley & Sons, Ltd.

  20. hp Spectral element methods for three dimensional elliptic problems

    Indian Academy of Sciences (India)

    This is the first of a series of papers devoted to the study of h-p spec- .... element functions defined on mesh elements in the new system of variables with a uni- ... the spectral element functions on these elements and give construction of the stability .... By Hm( ), we denote the usual Sobolev space of integer order m ≥ 0 ...

  1. Oxonium ions substituting cesium ions in the structure of the new high-pressure borate HP-Cs{sub 1-x}(H{sub 3}O){sub x}B{sub 3}O{sub 5} (x=0.5-0.7)

    Energy Technology Data Exchange (ETDEWEB)

    Sohr, Gerhard; Heymann, Gunter; Wurst, Klaus; Huppertz, Hubert [Institut fuer Allgemeine, Anorganische und Theoretische Chemie, Leopold-Franzens-Universitaet Innsbruck (Austria); Neumair, Stephanie C. [Tyrolit Schleifmittelwerke Swarovski K.G., Schwaz (Austria); Schmedt auf der Guenne, Joern [Department fuer Chemie und Biologie, Universitaet Siegen (Germany)

    2014-04-07

    The new high-pressure borate HP-Cs{sub 1-x}(H{sub 3}O){sub x}B{sub 3}O{sub 5} (x=0.5-0.7) was synthesized under high-pressure/high-temperature conditions of 6 GPa/900 C in a Walker-type multianvil apparatus. The compound crystallizes in the monoclinic space group C2/c (Z=8) with the parameters a=1000.6(2), b=887.8(2), c=926.3(2) pm, β=103.1(1) , V=0.8016(3) nm{sup 3}, R1=0.0452, and wR2=0.0721 (all data). The boron-oxygen network is analogous to those of the compounds HP-MB{sub 3}O{sub 5}, (M=K, Rb) and exhibits all three structural motifs of borates - BO{sub 3} groups, corner-sharing BO{sub 4} tetrahedra, and edge-sharing BO{sub 4} tetrahedra - at the same time. Channels inside the boron-oxygen framework contain the cesium and oxonium ions, which are disordered on a specific site. Estimating the amount of hydrogen by solid-state NMR spectroscopy and X-ray diffraction led to the composition HP-Cs{sub 1-x}(H{sub 3}O){sub x}B{sub 3}O{sub 5} (x=0.5-0.7), which implies a nonzero phase width. (copyright 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  2. Physicochemical properties of calcium silicate-based formulations MTA Repair HP and MTA Vitalcem.

    Science.gov (United States)

    Guimarães, Bruno Martini; Prati, Carlo; Duarte, Marco Antonio Hungaro; Bramante, Clovis Monteiro; Gandolfi, Maria Giovanna

    2018-04-05

    This study aimed to analyze the following physicochemical properties: radiopacity, final setting time, calcium release, pH change, solubility, water sorption, porosity, surface morphology, and apatite-forming ability of two calcium silicate-based materials. We tested MTA Repair HP and MTA Vitalcem in comparison with conventional MTA, analyzing radiopacity and final setting time. Water absorption, interconnected pores and apparent porosity were measured after 24-h immersion in deionized water at 37°C. Calcium and pH were tested up to 28 d in deionized water. We analyzed data using two-way ANOVA with Student-Newman-Keuls tests (pcalcium release at 28 d (pcalcium phosphate on their surface after 28 d in HBSS. MTA Repair HP and MTA Vitalcem had extended alkalinizing activity and calcium release that favored calcium phosphate nucleation. The presence of the plasticizer in MTA HP might increase its solubility and porosity. The radiopacifier calcium tungstate can be used to replace bismuth oxide.

  3. Hypoxia-inducible factor-1 alpha has a key role in hypoxic preconditioning.

    Science.gov (United States)

    Taie, Satoshi; Ono, Junichiro; Iwanaga, Yasuyuki; Tomita, Shuhei; Asaga, Takehiko; Chujo, Kosuke; Ueki, Masaaki

    2009-08-01

    Sublethal hypoxia induces tolerance to subsequent hypoxic insults in a process known as hypoxic preconditioning (HP). Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a key transcription protein involved in the mechanism of HP. In this study, we investigated the effects of HP on tissue oxygenation and expression of HIF-1 alpha gene targets in the brain using neural cell-specific HIF-1 alpha-deficient mice. The animals were exposed to 8% oxygen for 3 hours. Twenty-four hours later, the oxygen partial pressure (pO(2)) of brain tissue and gene expression were measured during hypoxia. HP improved the pO(2) of brain tissue during subsequent hypoxia with upregulated inducible nitric oxide synthase in wild-type mice, whereas HP had no detectable effect in the mutant mice. Our results indicate that the protective effects of HP may be partially mediated by improving tissue oxygenation via HIF-1 alpha and inducible nitric oxide synthase.

  4. Comparison of Hyoid Bone Position Among Cleft Lip Palate and Normal Subjects

    International Nuclear Information System (INIS)

    Wahaj, A.; Erum, G.; Ahmed, I.

    2014-01-01

    Objective: To compare the hyoid bone position between cleft lip/palate and normal patients. Study Design: Cross-sectional analytical study. Place and Duration of Study: Dr. Ishrat-ul-Ebad Khan Institute of Oral Health Sciences (DIEKIOHS), Dow University of Health Sciences (DUHS), Karachi, from March 2012 to February 2013. Methodology: The sample for this study consisted of total 68 subjects among which Group 1 consisted of 34 nonsyndromic cleft lip and palate (both unilateral and bilateral) and Group 2 included 34 subjects with normal facial morphology. Both groups included males and females with mean age 14.3 +- 0.1 year. Analysis was done on lateral cephalometric radiographs of patients including angulations taken as Hp-Mp, Hp-Ol, Hp-Sn, Cvt-Evt, Opt-Cvt, Nke, Sn-Vert, Cvt-Vert, Sn-Vert and linear distance of hyoid bone measured as C3-H, C3-RGN, and H-RGN. Results: Statistically significant differences (p < 0.001) in C3-H, C3-Rgn, H-Rgn, and Sn-Cvt were found between cleft lip/palate group and normal group. Conclusion: Hyoid bone is located anteriorly and caudally in cleft lip and palate group. (author)

  5. Hydrostatic Pressure Regulates MicroRNA Expression Levels in Osteoarthritic Chondrocyte Cultures via the Wnt/β-Catenin Pathway

    Directory of Open Access Journals (Sweden)

    Sara Cheleschi

    2017-01-01

    Full Text Available Mechanical loading and hydrostatic pressure (HP regulate chondrocytes’ metabolism; however, how mechanical stimulation acts remain unclear. MicroRNAs (miRNAs play an important role in cartilage homeostasis, mechanotransduction, and in the pathogenesis of osteoarthritis (OA. This study investigated the effects of a cyclic HP (1–5 MPa, in both normal and OA human chondrocytes, on the expression of miR-27a/b, miR-140, miR-146a/b, and miR-365, and of their target genes (MMP-13, ADAMTS-5, IGFBP-5, and HDAC-4. Furthermore, we assessed the possible involvement of Wnt/β-catenin pathway in response to HP. Chondrocytes were exposed to HP for 3h and the evaluations were performed immediately after pressurization, and following 12, 24, and 48 h. Total RNA was extracted and used for real-time PCR. β-catenin was detected by Western blotting analysis and immunofluorescence. In OA chondrocytes, HP induced a significant increase (p < 0.01 of the expression levels of miR-27a/b, miR-140, and miR-146a, and a significant reduction (p < 0.01 of miR-365 at all analyzed time points. MMP-13, ADAMTS-5, and HDAC-4 were significantly downregulated following HP, while no significant modification was found for IGFBP-5. β-catenin levels were significantly increased (p < 0.001 in OA chondrocytes at basal conditions and significantly reduced (p < 0.01 by HP. Pressurization did not cause any significant modification in normal cells. In conclusion, in OA chondrocytes, HP restores the expression levels of some miRNAs, downregulates MMP-13, ADAMTS-5, and HDAC-4, and modulates the Wnt/β-catenin pathway activation.

  6. Mua (HP0868) Is a Nickel-Binding Protein That Modulates Urease Activity in Helicobacter pylori

    Science.gov (United States)

    Benoit, Stéphane L.; Maier, Robert J.

    2011-01-01

    A novel mechanism aimed at controlling urease expression in Helicobacter pylori in the presence of ample nickel is described. Higher urease activities were observed in an hp0868 mutant (than in the wild type) in cells supplemented with nickel, suggesting that the HP0868 protein (herein named Mua for modulator of urease activity) represses urease activity when nickel concentrations are ample. The increase in urease activity in the Δmua mutant was linked to an increase in urease transcription and synthesis, as shown by quantitative real-time PCR, SDS-PAGE, and immunoblotting against UreAB. Increased urease synthesis was also detected in a Δmua ΔnikR double mutant strain. The Δmua mutant was more sensitive to nickel toxicity but more resistant to acid challenge than was the wild-type strain. Pure Mua protein binds 2 moles of Ni2+ per mole of dimer. Electrophoretic mobility shift assays did not reveal any binding of Mua to the ureA promoter or other selected promoters (nikR, arsRS, 5′ ureB-sRNAp). Previous yeast two-hybrid studies indicated that Mua and RpoD may interact; however, only a weak interaction was detected via cross-linking with pure components and this could not be verified by another approach. There was no significant difference in the intracellular nickel level between wild-type and mua mutant cells. Taken together, our results suggest the HP0868 gene product represses urease transcription when nickel levels are high through an as-yet-uncharacterized mechanism, thus counterbalancing the well-described NikR-mediated activation. PMID:21505055

  7. Developmentally regulated GTP-binding protein 2 is required for stabilization of Rac1-positive membrane tubules.

    Science.gov (United States)

    Mani, Muralidharan; Lee, Unn Hwa; Yoon, Nal Ae; Yoon, Eun Hye; Lee, Byung Ju; Cho, Wha Ja; Park, Jeong Woo

    2017-11-04

    Previously we have reported that developmentally regulated GTP-binding protein 2 (DRG2) localizes on Rab5 endosomes and plays an important role in transferrin (Tfn) recycling. We here identified DRG2 as a key regulator of membrane tubule stability. At 30 min after Tfn treatment, DRG2 localized to membrane tubules which were enriched with phosphatidylinositol 4-monophosphate [PI(4)P] and did not contain Rab5. DRG2 interacted with Rac1 more strongly with GTP-bound Rac1 and tubular localization of DRG2 depended on Rac1 activity. DRG2 depletion led to destabilization of membrane tubules, while ectopic expression of DRG2 rescued the stability of the membrane tubules in DRG2-depleted cells. Our results reveal a novel mechanism for regulation of membrane tubule stability mediated by DRG2. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Software quality assurance documentation for the release of NUFT 2.0 for HP platforms

    International Nuclear Information System (INIS)

    Fernandez, M.W.; Preckshot, G.G.; Johnson, G.L.

    1998-01-01

    This document is the Individual Software Plan (ISP) for version 2.0 of the Non-isothermal Unsaturated-saturated Flow and Transport (NUFT.) analysis computer program. This document addresses the applicable requirements of LLNL YMP procedure 033-YMP-QP 3.2, Section 4.2.1.1. The purpose of this ISP is to plan and organize the activities required to certify the NUFT code for quality affecting work involving problems that include cross drift analysis of the Yucca Mountain Repository facility. NUFT is software for application to the solution of a class of coupled mass and heat transport problems in porous geologic media including Yucca Mountain Repository Cross Drift Problem (YMRCDP- also known as the Enhanced Characterization of the Repository Block (ECRB)). Solution of this class of problems requires a suite of multiphase, multi-component models for numerical solution of non- isothermal flow and transport in porous media with applications to subsurface contaminant transport problems. NUFT is a suite of multiphase, multi-component models for numerical solution of non- isothermal flow and transport in porous media, with application to subsurface contaminant transport problems, and in particular, to the hydrology in and about the Yucca Mountain Repository Site. NUFI is acquired software, as defined by 033-YMP-QP 3.2, and a preliminary baseline of source code, electronic documentation, and paper documentation has been established as required by 033-YMP-QP 3.2, Section 4.1. NUFT runs on Sun Unix platforms, Solaris operating system version 5.5 and HP-UX with operating system version 10.20. The product to be qualified under this ISP is the version running on HP- UX. The HP version will be labeled Version 2.0h. The h is included to distinguish the HP version from possible future versions qualified for Sun or other platforms. The scope of the plans and procedures outlined in this ISP is limited to the effort required to qualify NUFT for the class of problems identified in

  9. Non-Canonical Hedgehog Signaling Is a Positive Regulator of the WNT Pathway and Is Required for the Survival of Colon Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Joseph L. Regan

    2017-12-01

    Full Text Available Summary: Colon cancer is a heterogeneous tumor driven by a subpopulation of cancer stem cells (CSCs. To study CSCs in colon cancer, we used limiting dilution spheroid and serial xenotransplantation assays to functionally define the frequency of CSCs in a panel of patient-derived cancer organoids. These studies demonstrated cancer organoids to be enriched for CSCs, which varied in frequency between tumors. Whole-transcriptome analysis identified WNT and Hedgehog signaling components to be enhanced in CSC-enriched tumors and in aldehyde dehydrogenase (ALDH-positive CSCs. Canonical GLI-dependent Hedgehog signaling is a negative regulator of WNT signaling in normal intestine and intestinal tumors. Here, we show that Hedgehog signaling in colon CSCs is autocrine SHH-dependent, non-canonical PTCH1 dependent, and GLI independent. In addition, using small-molecule inhibitors and RNAi against SHH-palmitoylating Hedgehog acyltransferase (HHAT, we demonstrate that non-canonical Hedgehog signaling is a positive regulator of WNT signaling and required for colon CSC survival. : Colon cancer is a heterogeneous tumor driven by a subpopulation(s of therapy-resistant cancer stem cells (CSCs. Regan et al. use 3D culture models to demonstrate that CSC survival is regulated by non-canonical, SHH-dependent, PTCH1-dependent Hedgehog signaling, which acts as a positive regulator of WNT signaling to block CSC differentiation. Keywords: WNT pathway, non-canonical Hedgehog signaling, cancer stem cell, colon cancer, cancer organoid, PTCH1, HHAT, SHH

  10. Categorizing Mistaken False Positives in Regulation of Human and Environmental Health

    DEFF Research Database (Denmark)

    Hansen, Steffen Foss; Krayer von Krauss, Martin Paul; Tickner, J.A.

    2007-01-01

    One of the concerns often voiced by critics of the precautionary principle is that a widespread regulatory application of the principle will lead to a large number of false positives (i.e., over-regulation of minor risks and regulation of nonexisting risks). The present article proposes a general......," including: real risks, "The jury is still out," nonregulated proclaimed risks, "Too narrow a definition of risk," and risk-risk tradeoffs. These categories are defined and examples are presented in order to illustrate their key characteristics. On the basis of our analysis, we were able to identify only...... four cases that could be defined as regulatory false positives in the light of today's knowledge and recognized uncertainty: the Southern Corn Leaf Blight, the Swine Flu, Saccharin, and Food Irradiation in relation to consumer health. We conclude that concerns about false positives do not represent...

  11. Tensor analyzing power T20 of the dd →3Hen and dd →3Hp reactions at zero angle for energies 140, 200, and 270 MeV

    International Nuclear Information System (INIS)

    Ladygin, V. P.; Uesaka, T.; Saito, T.; Hatano, M.; Isupov, A. Yu.; Kato, H.; Ladygina, N. B.; Maeda, Y.; Malakhov, A. I.; Nishikawa, J.; Ohnishi, T.; Okamura, H.; Reznikov, S. G.; Sakai, H.; Sakamoto, N.; Sakoda, S.; Satou, Y.; Sekiguchi, K.; Suda, K.; Tamii, A.

    2006-01-01

    RIKEN Accelerator Research Facility data on the tensor analyzing power T 20 of the dd → 3 Hen and dd → 3 Hp reactions at zero angle for deuteron kinetic energies of 140, 200, and 270 MeV are reported. The observed positive sign of T 20 clearly demonstrates the sensitivity to the D/S-wave ratio in the 3 He and 3 H wave functions in the energy range of the experiment. Data on T 20 for the 3 Hen channel are in agreement with those for the 3 Hp channel within the experimental errors

  12. Sphingosine-1-phosphate (S1P) enhances glomerular endothelial cells activation mediated by anti-myeloperoxidase antibody-positive IgG.

    Science.gov (United States)

    Sun, Xiao-Jing; Chen, Min; Zhao, Ming-Hui

    2018-03-01

    Cumulating evidences suggested an important role of sphingosine-1-phosphate (S1P) and its receptors in regulating endothelial barrier integrity. Our previous study revealed that the circulating S1P levels and renal expression of S1PRs correlated with disease activity and renal damage in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This study investigated the role of S1P and its receptors in myeloperoxidase (MPO)-ANCA-positive IgG-mediated glomerular endothelial cell (GEnC) activation. The effect of S1P on morphological alteration of GEnCs in the presence of MPO-ANCA-positive IgG was observed. Permeability assay was performed to determine endothelial monolayer activation in quantity. Both membrane-bound and soluble ICAM-1 and VCAM-1 levels were measured. Furthermore, antagonists and/or agonists of various S1PRs were employed to determine the role of different S1PRs. S1P enhanced MPO-ANCA-positive IgG-induced disruption of tight junction and disorganization of cytoskeleton in GEnCs. S1P induced further increase in monolayer permeability of GEnC monolayers in the presence of MPO-ANCA-positive IgG. S1P enhanced MPO-ANCA-positive IgG-induced membrane-bound and soluble ICAM-1/VCAM-1 up-regulation of GEnCs. Soluble ICAM-1 levels in the supernatants of GEnCs stimulated by S1P and MPO-ANCA-positive IgG increased upon pre-incubation of S1PR1 antagonist, while pre-incubation of GEnCs with the S1PR1 agonist down-regulated sICAM-1 level. Blocking S1PR2-4 reduced sICAM-1 levels in the supernatants of GEnCs stimulated by S1P and MPO-ANCA-positive IgG. Pre-incubation with S1PR5 agonist could increase sICAM-1 level in the supernatants of GEnC stimulated by S1P and MPO-ANCA-positive IgG. S1P can enhance MPO-ANCA-positive IgG-mediated GEnC activation through S1PR2-5. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  13. Regulation of UGT1A1 and HNF1 transcription factor gene expression by DNA methylation in colon cancer cells

    Directory of Open Access Journals (Sweden)

    Harvey Mario

    2010-01-01

    Full Text Available Abstract Background UDP-glucuronosyltransferase 1A1 (UGT1A1 is a pivotal enzyme involved in metabolism of SN-38, the active metabolite of irinotecan commonly used to treat metastatic colorectal cancer. We previously demonstrated aberrant methylation of specific CpG dinucleotides in UGT1A1-negative cells, and revealed that methylation state of the UGT1A1 5'-flanking sequence is negatively correlated with gene transcription. Interestingly, one of these CpG dinucleotides (CpG -4 is found close to a HNF1 response element (HRE, known to be involved in activation of UGT1A1 gene expression, and within an upstream stimulating factor (USF binding site. Results Gel retardation assays revealed that methylation of CpG-4 directly affect the interaction of USF1/2 with its cognate sequence without altering the binding for HNF1-alpha. Luciferase assays sustained a role for USF1/2 and HNF1-alpha in UGT1A1 regulation in colon cancer cells. Based on the differential expression profiles of HNF1A gene in colon cell lines, we also assessed whether methylation affects its expression. In agreement with the presence of CpG islands in the HNF1A promoter, treatments of UGT1A1-negative HCT116 colon cancer cells with a DNA methyltransferase inhibitor restore HNF1A gene expression, as observed for UGT1A1. Conclusions This study reveals that basal UGT1A1 expression in colon cells is positively regulated by HNF1-alpha and USF, and negatively regulated by DNA methylation. Besides, DNA methylation of HNF1A could also play an important role in regulating additional cellular drug metabolism and transporter pathways. This process may contribute to determine local inactivation of drugs such as the anticancer agent SN-38 by glucuronidation and define tumoral response.

  14. [Relationships between the enrichment of ETBF, Fn, Hp in intestinal and colorectal cancer].

    Science.gov (United States)

    Zhang, J; Lu, X L; Zhao, G; Shi, H T; Geng, Y; Zhong, W T; Dong, L

    2018-02-23

    Objective: To explore relationships between the enrichment of ETBF, Fn, Hp in feces, tissues and colorectal cancer. Methods: Feces, lesion tissue and adjacent tissue from 24 patients with colorectal cancer and 31 patients with adenomas were collected, and we collected Feces and tissue of 20 healthy control persons. Then the copy numbers of enterotoxigenic B. fragilis (ETBF), Fusobacterium nucleatum (Fn) and Helicobacter pylori (Hp) were determined by quantitative real-time PCR. Immunohistochemical method was used to examine the expression intensity of EGFR and p53, and the relationships between different expression intensity of EGFR, p53 and the numbers of three bacterias. Results: In the feces, copy numbers of ETBF and Fn were as follous: colorectal cancer group>adenomas group>healthy control group ( P healthy control group ( P healthy control group ( P adenomas group>healthy control group ( P healthy control group ( P healthy control group ( P bacteria in the lesion tissue and the adjacent tissue had no significant difference. This happened both in colorectal cancer group and adenomas group. The different expression intensity of EGFR, p53 and the number of three bacteria showed no obviously statistical correlation( P >0.05). Conclusion: Adenomatous polyp and colorectal cancer patients show high enrichment of ETBF, Fn and Hp in both feces and tissues. ETBF, Fn and Hp probably contribute to the development of adenomatous polyp and colorectal cancer. Trial registration Chinese Clinical Trial Registry, ChiCTR-BOC-17012509.

  15. The tensor analyzing power T20 in the dd → 3Hen and dd → 3Hp reactions at the energies 140, 200 and 270 MeV at zero angle

    International Nuclear Information System (INIS)

    Ladygin, V.P.; ); Uesaka, T.; Saito, T.

    2006-01-01

    The data on the tensor analyzing power T 20 in the dd → 3 Hen and dd → 3 Hp reactions at 140, 200 and 270 MeV of the deuteron kinetic energy and at zero angle obtained at RIKEN Accelerator Research Facility are presented. The observed positive sign of T 20 clearly demonstrates the sensitivity to the D/S wave ratios in the 3 He and 3 H in the energy domain of the measurements. The T 20 data for the 3 Hen and 3 Hp channels are in agreement within experimental accuracy [ru

  16. Helicobacter pylori HP1034 (ylxH) is required for motility

    NARCIS (Netherlands)

    van Amsterdam, Karin; van der Ende, Arie

    2004-01-01

    Background. Helicobacter pylori motility is essential for the colonization and persistence in the human gastric mucosa. So far, more than 50 genes have been described to play a role in flagellar biosynthesis. H. pylori YlxH (HP1034) is annotated as an ATP-binding protein. However, H. pylori YlxH

  17. Transcription Factor Foxo1 Is a Negative Regulator of NK Cell Maturation and Function

    Science.gov (United States)

    Deng, Youcai; Kerdiles, Yann; Chu, Jianhong; Yuan, Shunzong; Wang, Youwei; Chen, Xilin; Mao, Hsiaoyin; Zhang, Lingling; Zhang, Jianying; Hughes, Tiffany; Deng, Yafei; Zhang, Qi; Wang, Fangjie; Zou, Xianghong; Liu, Chang-Gong; Freud, Aharon G.; Li, Xiaohui; Caligiuri, Michael A; Vivier, Eric; Yu, Jianhua

    2015-01-01

    SUMMARY Little is known about the role of negative regulators in controlling natural killer (NK) cell development and effector functions. Foxo1 is a multifunctional transcription factor of the forkhead family. Using a mouse model of conditional deletion in NK cells, we found that Foxo1 negatively controlled NK cell differentiation and function. Immature NK cells expressed abundant Foxo1 and little Tbx21 relative to mature NK cells, but these two transcription factors reversed their expression as NK cells proceeded through development. Foxo1 promoted NK cell homing to lymph nodes through upregulating CD62L expression, and impaired late-stage maturation and effector functions by repressing Tbx21 expression. Loss of Foxo1 rescued the defect in late-stage NK cell maturation in heterozygous Tbx21+/− mice. Collectively, our data reveal a regulatory pathway by which the negative regulator Foxo1 and the positive regulator Tbx21 play opposing roles in controlling NK cell development and effector functions. PMID:25769609

  18. β-Catenin Is a Positive Regulator of Estrogen Receptor-α Function in Breast Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Nibedita; Schmitt, Fee; Grebhardt, Sina; Mayer, Doris, E-mail: d.mayer@dkfz.de [Hormones and Signal Transduction Group, German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, 69120 Heidelberg (Germany)

    2011-07-22

    Estrogen receptor-alpha (ERα) is a key factor in the development of breast cancer in humans. The expression and activity of ERα is regulated by a multitude of intracellular and extracellular signals. Here we show a cross-talk between β-catenin and ERα in human breast cancer cells. Knockdown of β-catenin by RNAi resulted in significant reduction of ERα mRNA and/or protein levels in MCF-7, T-47D, and BT-474 breast cancer cells and in significant reduction of estradiol-induced expression of the ERα target genes pS2 and GREB1. In addition β-catenin silencing resulted in significant decrease of growth of MCF-7 cells both in the absence and presence of estradiol. β-catenin and ERα could not be co-immunoprecipitated by ERα antibodies from lysates of E2-treated or untreated cells suggesting lack of direct physical interaction. It is concluded that β-catenin is a positive regulator of ERα mRNA and protein expression.

  19. A Flexible Binding Site Architecture Provides New Insights into CcpA Global Regulation in Gram-Positive Bacteria

    Directory of Open Access Journals (Sweden)

    Yunpeng Yang

    2017-01-01

    Full Text Available Catabolite control protein A (CcpA is the master regulator in Gram-positive bacteria that mediates carbon catabolite repression (CCR and carbon catabolite activation (CCA, two fundamental regulatory mechanisms that enable competitive advantages in carbon catabolism. It is generally regarded that CcpA exerts its regulatory role by binding to a typical 14- to 16-nucleotide (nt consensus site that is called a catabolite response element (cre within the target regions. However, here we report a previously unknown noncanonical flexible architecture of the CcpA-binding site in solventogenic clostridia, providing new mechanistic insights into catabolite regulation. This novel CcpA-binding site, named crevar, has a unique architecture that consists of two inverted repeats and an intervening spacer, all of which are variable in nucleotide composition and length, except for a 6-bp core palindromic sequence (TGTAAA/TTTACA. It was found that the length of the intervening spacer of crevar can affect CcpA binding affinity, and moreover, the core palindromic sequence of crevar is the key structure for regulation. Such a variable architecture of crevar shows potential importance for CcpA’s diverse and fine regulation. A total of 103 potential crevar sites were discovered in solventogenic Clostridium acetobutylicum, of which 42 sites were picked out for electrophoretic mobility shift assays (EMSAs, and 30 sites were confirmed to be bound by CcpA. These 30 crevar sites are associated with 27 genes involved in many important pathways. Also of significance, the crevar sites are found to be widespread and function in a great number of taxonomically different Gram-positive bacteria, including pathogens, suggesting their global role in Gram-positive bacteria.

  20. A Case of Monoclonal Lymphoplasmacytosis of the Bone Marrow with IgM-Positive Russell Bodies

    Directory of Open Access Journals (Sweden)

    Hidekazu Kayano

    2011-01-01

    Full Text Available A 71-year-old Japanese male patient infected with HCV was diagnosed with thrombocytopenia. Histological examination of the bone marrow aspirate showed numerous lymphoid aggregates with Russell bodies. Immunohistochemistry and flow cytometric analysis demonstrated clonal expansion of CD5+ CD23+ B cells. Russell bodies were positive for IgM and lambda immunoglobulin light chain. The patient also underwent gastric biopsy, which revealed Helicobacter pylori (HP infection. Subsequent eradication of the bacteria resulted in improvement of his thrombocytopenia. The clinical course remained uneventful at 15-month follow-up, consistent with monoclonal B-cell lymphocytosis. The observed clonal expansion with plasmacytic differentiation may have occurred under the influence of HCV with HP infection.

  1. Gr and hp-1 tomato mutants unveil unprecedented interactions between arbuscular mycorrhizal symbiosis and fruit ripening.

    Science.gov (United States)

    Chialva, Matteo; Zouari, Inès; Salvioli, Alessandra; Novero, Mara; Vrebalov, Julia; Giovannoni, James J; Bonfante, Paola

    2016-07-01

    Systemic responses to an arbuscular mycorrhizal fungus reveal opposite phenological patterns in two tomato ripening mutants depending whether ethylene or light reception is involved. The availability of tomato ripening mutants has revealed many aspects of the genetics behind fleshy fruit ripening, plant hormones and light signal reception. Since previous analyses revealed that arbuscular mycorrhizal symbiosis influences tomato berry ripening, we wanted to test the hypothesis that an interplay might occur between root symbiosis and fruit ripening. With this aim, we screened seven tomato mutants affected in the ripening process for their responsiveness to the arbuscular mycorrhizal fungus Funneliformis mosseae. Following their phenological responses we selected two mutants for a deeper analysis: Green ripe (Gr), deficient in fruit ethylene perception and high-pigment-1 (hp-1), displaying enhanced light signal perception throughout the plant. We investigated the putative interactions between ripening processes, mycorrhizal establishment and systemic effects using biochemical and gene expression tools. Our experiments showed that both mutants, notwithstanding a normal mycorrhizal phenotype at root level, exhibit altered arbuscule functionality. Furthermore, in contrast to wild type, mycorrhization did not lead to a higher phosphate concentration in berries of both mutants. These results suggest that the mutations considered interfere with arbuscular mycorrhiza inducing systemic changes in plant phenology and fruits metabolism. We hypothesize a cross talk mechanism between AM and ripening processes that involves genes related to ethylene and light signaling.

  2. Ly49Q, an ITIM-bearing NK receptor, positively regulates osteoclast differentiation

    International Nuclear Information System (INIS)

    Hayashi, Mikihito; Nakashima, Tomoki; Kodama, Tatsuhiko; Makrigiannis, Andrew P.; Toyama-Sorimachi, Noriko; Takayanagi, Hiroshi

    2010-01-01

    Osteoclasts, multinucleated cells that resorb bone, play a key role in bone remodeling. Although immunoreceptor tyrosine-based activation motif (ITAM)-mediated signaling is critical for osteoclast differentiation, the significance of immunoreceptor tyrosine-based inhibitory motif (ITIM) has not been well understood. Here we report the function of Ly49Q, an Ly49 family member possessing an ITIM motif, in osteoclastogenesis. Ly49Q is selectively induced by receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL) stimulation in bone marrow-derived monocyte/macrophage precursor cells (BMMs) among the Ly49 family of NK receptors. The knockdown of Ly49Q resulted in a significant reduction in the RANKL-induced formation of tartrate-resistance acid phosphatase (TRAP)-positive multinucleated cells, accompanied by a decreased expression of osteoclast-specific genes such as Nfatc1, Tm7sf4, Oscar, Ctsk, and Acp5. Osteoclastogenesis was also significantly impaired in Ly49Q-deficient cells in vitro. The inhibitory effect of Ly49Q-deficiency may be explained by the finding that Ly49Q competed for the association of Src-homology domain-2 phosphatase-1 (SHP-1) with paired immunoglobulin-like receptor-B (PIR-B), an ITIM-bearing receptor which negatively regulates osteoclast differentiation. Unexpectedly, Ly49Q deficiency did not lead to impaired osteoclast formation in vivo, suggesting the existence of a compensatory mechanism. This study provides an example in which an ITIM-bearing receptor functions as a positive regulator of osteoclast differentiation.

  3. Studying the Efficiency of XAD-7HP Anionic Resin in the Extraction of Humic Acid from Surface Water

    Directory of Open Access Journals (Sweden)

    Hassan Hashemi

    2017-09-01

    Results: The average extraction efficiency for XAD-7HP was 77% and HA concentration determined in all seasons ranges from 0.15 to 0.29 mg/L in raw water. Conclusions: From the findings of this study, it can be concluded that the use of XAD-7HP is a proper and effective method for the extraction of HS and its extraction efficiency is more influenced by pH and turbidity than other parameters. It can also be deduced from this study that XAD-7HP resin was most efficient at a pH of 2 and an increase in turbidity resulted in a corresponding decrease in the efficiency of resin.

  4. Presence of serum antibodies to influenza A subtypes H5 and N1 in swans and ibises in French wetlands, irrespective of highly pathogenic H5N1 natural infection.

    Science.gov (United States)

    Niqueux, Eric; Guionie, Olivier; Schmitz, Audrey; Hars, Jean; Jestin, Véronique

    2010-03-01

    Highly pathogenic (HP) avian influenza A viruses (AIVs) subtype H5N1 (subclade 2.2) were detected in wild birds during outbreaks in France during winter 2006 and summer 2007 in la Dombes wetlands (eastern France) and in Moselle wetlands (northeastern France), respectively. Blood samples from apparently healthy wild birds were collected in 2006 and 2007 from the end of the outbreak to several weeks after the influenza A outbreak inside and outside the contaminated areas, and in 2008 outside the contaminated areas. The samples were tested for the presence and/or quantitation of serum antibodies to influenza A subtypes H5 and N1 using hemagglutination inhibition tests (HITs), a commercial N1-specific enzyme-linked immunosorbent assay kit, and virus neutralization assay. In the HIT, low pathogenicity (LP) and HP H5 AIVs (belonging to H5N1, H5N2, and H5N3 subtypes) were used as antigens. One hundred mute swans were bled in the la Dombes outbreak area in 2006. During 2007, 46 mallards, 69 common pochards, and 59 mute swans were sampled in the Moselle outbreak area. For comparison, blood samples were also collected in 2007 from 60 mute swans from the Marne department where no HP H5N1 influenza A cases have been reported, and in 2008 from 111 sacred ibises in western France where no HP H5N1 influenza A infections in wild birds have been reported either. Mute swans (irrespective of their origin and time of sampling) and sacred ibises (from an area with no known outbreaks) had the highest prevalence of positive sera in the H5 HIT (49-69% and 64%, respectively). The prevalence of anti-H5 antibodies in mallards and common pochards was lower (28% and 27%, respectively). Positive H5- and N1-antibody responses were also significantly associated in swans (irrespective of their origin and time of sampling) and in sacred ibises. However, in swans from the area without outbreaks, the HIT titer against an H5N1 LPAIV was significantly higher than against an H5N1 2.2.1 HPAIV, whereas no

  5. Discrete maximum principle for Poisson equation with mixed boundary conditions solved by hp-FEM

    Czech Academy of Sciences Publication Activity Database

    Vejchodský, Tomáš; Šolín, P.

    2009-01-01

    Roč. 1, č. 2 (2009), s. 201-214 ISSN 2070-0733 R&D Projects: GA AV ČR IAA100760702; GA ČR(CZ) GA102/07/0496; GA ČR GA102/05/0629 Institutional research plan: CEZ:AV0Z10190503 Keywords : discrete maximum principle * hp-FEM * Poisson equation * mixed boundary conditions Subject RIV: BA - General Mathematics

  6. Positive regulation of raphe serotonin neurons by serotonin 2B receptors.

    Science.gov (United States)

    Belmer, Arnauld; Quentin, Emily; Diaz, Silvina L; Guiard, Bruno P; Fernandez, Sebastian P; Doly, Stéphane; Banas, Sophie M; Pitychoutis, Pothitos M; Moutkine, Imane; Muzerelle, Aude; Tchenio, Anna; Roumier, Anne; Mameli, Manuel; Maroteaux, Luc

    2018-06-01

    Serotonin is a neurotransmitter involved in many psychiatric diseases. In humans, a lack of 5-HT 2B receptors is associated with serotonin-dependent phenotypes, including impulsivity and suicidality. A lack of 5-HT 2B receptors in mice eliminates the effects of molecules that directly target serotonergic neurons including amphetamine derivative serotonin releasers, and selective serotonin reuptake inhibitor antidepressants. In this work, we tested the hypothesis that 5-HT 2B receptors directly and positively regulate raphe serotonin neuron activity. By ex vivo electrophysiological recordings, we report that stimulation by the 5-HT 2B receptor agonist, BW723C86, increased the firing frequency of serotonin Pet1-positive neurons. Viral overexpression of 5-HT 2B receptors in these neurons increased their excitability. Furthermore, in vivo 5-HT 2B -receptor stimulation by BW723C86 counteracted 5-HT 1A autoreceptor-dependent reduction in firing rate and hypothermic response in wild-type mice. By a conditional genetic ablation that eliminates 5-HT 2B receptor expression specifically and exclusively from Pet1-positive serotonin neurons (Htr2b 5-HTKO mice), we demonstrated that behavioral and sensitizing effects of MDMA (3,4-methylenedioxy-methamphetamine), as well as acute behavioral and chronic neurogenic effects of the antidepressant fluoxetine, require 5-HT 2B receptor expression in serotonergic neurons. In Htr2b 5-HTKO mice, dorsal raphe serotonin neurons displayed a lower firing frequency compared to control Htr2b lox/lox mice as assessed by in vivo extracellular recordings and a stronger hypothermic effect of 5-HT 1A -autoreceptor stimulation was observed. The increase in head-twitch response to DOI (2,5-dimethoxy-4-iodoamphetamine) further confirmed the lower serotonergic tone resulting from the absence of 5-HT 2B receptors in serotonin neurons. Together, these observations indicate that the 5-HT 2B receptor acts as a direct positive modulator of serotonin Pet1

  7. COOLII code conversion from Cyber to HP

    International Nuclear Information System (INIS)

    Lee, Hae Cho; Kim, Hee Kyung

    1996-06-01

    COOLII computer code determines the time required to cooldown the plant from shutdown cooling system initiation condition to cold shutdown or refueling condition. Required time for cooldown is calculated under the various assumption on shutdown cooling heat exchanger(SDCHX) availability, reactor coolant system (RCS) low pressure safety injection(LPSI) flowrate. RCS cooldown rates and component cooling system flow rates. This report firstly describes detailed work carried out for installation of COOLII on HP 9000/700 series as well as relevant code validation results. Attached is a report on software verification and validation results. 7 refs. (Author) .new

  8. Growth/differentiation factor 15 promotes EGFR signalling, and regulates proliferation and migration in the hippocampus of neonatal and young adult mice.

    Science.gov (United States)

    Carrillo-García, Carmen; Prochnow, Sebastian; Simeonova, Ina K; Strelau, Jens; Hölzl-Wenig, Gabriele; Mandl, Claudia; Unsicker, Klaus; von Bohlen Und Halbach, Oliver; Ciccolini, Francesca

    2014-02-01

    The activation of epidermal growth factor receptor (EGFR) affects multiple aspects of neural precursor behaviour, including proliferation and migration. Telencephalic precursors acquire EGF responsiveness and upregulate EGFR expression at late stages of development. The events regulating this process and its significance are still unclear. We here show that in the developing and postnatal hippocampus (HP), growth/differentiation factor (GDF) 15 and EGFR are co-expressed in primitive precursors as well as in more differentiated cells. We also provide evidence that GDF15 promotes responsiveness to EGF and EGFR expression in hippocampal precursors through a mechanism that requires active CXC chemokine receptor (CXCR) 4. Besides EGFR expression, GDF15 ablation also leads to decreased proliferation and migration. In particular, lack of GDF15 impairs both processes in the cornu ammonis (CA) 1 and only proliferation in the dentate gyrus (DG). Importantly, migration and proliferation in the mutant HP were altered only perinatally, when EGFR expression was also affected. These data suggest that GDF15 regulates migration and proliferation by promoting EGFR signalling in the perinatal HP and represent a first description of a functional role for GDF15 in the developing telencephalon.

  9. Spectral/hp element methods for CFD

    CERN Document Server

    Karniadakis, George Em

    1999-01-01

    Traditionally spectral methods in fluid dynamics were used in direct and large eddy simulations of turbulent flow in simply connected computational domains. The methods are now being applied to more complex geometries, and the spectral/hp element method, which incorporates both multi-domain spectral methods and high-order finite element methods, has been particularly successful. This book provides a comprehensive introduction to these methods. Written by leaders in the field, the book begins with a full explanation of fundamental concepts and implementation issues. It then illustrates how these methods can be applied to advection-diffusion and to incompressible and compressible Navier-Stokes equations. Drawing on both published and unpublished material, the book is an important resource for experienced researchers and for those new to the field.

  10. N-Myc Differentially Regulates Expression of MXI1 Isoforms in Neuroblastoma1

    Science.gov (United States)

    Armstrong, Michael B; Mody, Rajen J; Ellis, D Christian; Hill, Adam B; Erichsen, David A; Wechsler, Daniel S

    2013-01-01

    Amplification of the MYCN proto-oncogene is associated with a poor prognosis in patients with metastatic neuroblastoma (NB). MYCN encodes the N-Myc protein, a transcriptional regulator that dimerizes with the Max transcription factor, binds to E-box DNA sequences, and regulates genes involved in cell growth and apoptosis. Overexpression of N-Myc leads to transcriptional activation and an increase in NB cell proliferation. Mxi1, a member of the Myc family of transcriptional regulators, also binds to Max. However, Mxi1 is a transcriptional repressor and inhibits proliferation of NB cells, suggesting that Mxi1 functions as an N-Myc antagonist. Our laboratory previously identified Mxi1-0, an alternatively transcribed Mxi1 isoform. Mxi1-0 has properties distinct from those of Mxi1; in contrast to Mxi1, Mxi1-0 is unable to suppress c-Myc-dependent transcription. We now show that Mxi1-0 expression increases in response to MYCN overexpression in NB cells, with a positive correlation between MYCN and MXI1-0 RNA levels. We also show that N-Myc expression differentially regulates the MXI1 and MXI1-0 promoters: Increased MYCN expression suppresses MXI1 promoter activity while enhancing transcription through the MXI1-0 promoter. Finally, induction of Mxi1-0 leads to increased proliferation, whereas expression of Mxi1 inhibits cell growth, indicating differential roles for these two proteins. These data suggest that N-Myc differentially regulates the expression of MXI1 and MXI1-0 and can alter the balance between the two transcription factors. Furthermore, MXI1-0 appears to be a downstream target of MYCN-dependent signaling pathways and may contribute to N-Myc-dependent cell growth and proliferation. PMID:24403858

  11. Multifaceted regulation of V(D)J recombination

    Science.gov (United States)

    Wang, Guannan

    V(D)J recombination is responsible for generating an enormous repertoire of immunoglobulins and T cell receptors, therefore it is a centerpiece to the formation of the adaptive immune system. The V(D)J recombination process proceeds through two steps, site-specific cleavage at RSS (Recombination Signal Sequence) site mediated by the RAG recombinase (RAG1/2) and the subsequent imprecise resolution of the DNA ends, which is carried out by the ubiquitous non-homologous end joining pathway (NHEJ). The V(D)J recombination reaction is obliged to be tightly controlled under all circumstances, as it involves generations of DNA double strand breaks, which are considered the most dangerous lesion to a cell. Multifaceted regulatory mechanisms have been evolved to create great diversity of the antigen receptor repertoire while ensuring genome stability. The RAG-mediated cleavage reaction is stringently regulated at both the pre-cleavage stage and the post-cleavage stage. Specifically, RAG1/2 first forms a pre-cleavage complex assembled at the boarder of RSS and coding flank, which ensures the appropriate DNA targeting. Subsequently, this complex initiates site-specific cleavage, generating two types of double stranded DNA breaks, hairpin-ended coding ends (HP-CEs) and blunt signal ends (SEs). After the cleavage, RAG1/2 proteins bind and retain the recombination ends to form post-cleavage complexes (PCC), which collaborates with the NHEJ machinery for appropriate transfer of recombination ends to NHEJ for proper end resolution. However, little is known about the molecular basis of this collaboration, partly attributed to the lack of sensitive assays to reveal the interaction of PCC with HP-CEs. Here, for the first time, by using two complementary fluorescence-based techniques, fluorescence anisotropy and fluorescence resonance energy transfer (FRET), I managed to monitor the RAG1/2-catalyzed cleavage reaction in real time, from the pre-cleavage to the post-cleavage stages. By

  12. HapX positively and negatively regulates the transcriptional response to iron deprivation in Cryptococcus neoformans.

    Directory of Open Access Journals (Sweden)

    Won Hee Jung

    2010-11-01

    Full Text Available The fungal pathogen Cryptococcus neoformans is a major cause of illness in immunocompromised individuals such as AIDS patients. The ability of the fungus to acquire nutrients during proliferation in host tissue and the ability to elaborate a polysaccharide capsule are critical determinants of disease outcome. We previously showed that the GATA factor, Cir1, is a major regulator both of the iron uptake functions needed for growth in host tissue and the key virulence factors such as capsule, melanin and growth at 37°C. We are interested in further defining the mechanisms of iron acquisition from inorganic and host-derived iron sources with the goal of understanding the nutritional adaptation of C. neoformans to the host environment. In this study, we investigated the roles of the HAP3 and HAPX genes in iron utilization and virulence. As in other fungi, the C. neoformans Hap proteins negatively influence the expression of genes encoding respiratory and TCA cycle functions under low-iron conditions. However, we also found that HapX plays both positive and negative roles in the regulation of gene expression, including a positive regulatory role in siderophore transporter expression. In addition, HapX also positively regulated the expression of the CIR1 transcript. This situation is in contrast to the negative regulation by HapX of genes encoding GATA iron regulatory factors in Aspergillus nidulans and Schizosaccharomyces pombe. Although both hapX and hap3 mutants were defective in heme utilization in culture, only HapX made a contribution to virulence, and loss of HapX in a strain lacking the high-affinity iron uptake system did not cause further attenuation of disease. Therefore, HapX appears to have a minimal role during infection of mammalian hosts and instead may be an important regulator of environmental iron uptake functions. Overall, these results indicated that C. neoformans employs multiple strategies for iron acquisition during infection.

  13. [PRODUCT OF THE BMI1--A KEY COMPONENT OF POLYCOMB--POSITIVELY REGULATES ADIPOCYTE DIFFERENTIATION OF MOUSE MESENCHYMAL STEM CELLS].

    Science.gov (United States)

    Petrov, N S; Vereschagina, N A; Sushilova, E N; Kropotov, A V; Miheeva, N F; Popov, B V

    2016-01-01

    Bmil is a key component of Polycomb (PcG), which in mammals controls the basic functions of mammalian somatic stem cells (SSC) such as self-renewal and differentiation. Bmi1 supports SSC via transcriptional suppression of genes associated with cell cycle and differentiation. The most studied target genes of Bmi1 are the genes of Ink4 locus, CdkI p16(Ink4a) and p1(Arf), suppression of which due to activating mutations of the BMI1 results in formation of cancer stem cells (CSC) and carcinomas in various tissues. In contrast, inactivation of BMI1 results in cell cycle arrest and cell senescence. Although clinical phenomena of hypo- and hyperactivation of BMI1 are well known, its targets and mechanisms of regulation of tissue specific SSC are still obscure. The goal of this study was to evaluate the regulatory role of BMI1 in adipocyte differentiation (AD) of mouse mesenchymal stem cells (MSC). Induction of AD in mouse MSC of the C3H10T1/2 cell line was associated with an increase in the expression levels of BMI1, the genes of pRb family (RB, p130) and demethylase UTX, but not methyltransferase EZH2, whose products regulate the methylation levels of H3K27. It was observed earlier that H3K27me3 may play the role of the epigenetic switch by promoting AD of human MSC via activating expression of the PPARγ2, the master gene of AD (Hemming et al., 2014). Here we show that inactivation of BMI1 using specific siRNA slows and decreases the levels of AD, but does not abolish it. This is associated with a complete inhibition of the expression of adipogenic marker genes--PPARγ2, ADIPOQ and a decrease in the expression of RB, p130, but not UTX. The results obtained give evidence that the epigenetic mechanism regulating AD differentiation in mouse and human MSC is different.

  14. Transcription Factor SmWRKY1 Positively Promotes the Biosynthesis of Tanshinones in Salvia miltiorrhiza

    Directory of Open Access Journals (Sweden)

    Wenzhi Cao

    2018-04-01

    Full Text Available Tanshinones, one group of bioactive diterpenes, were widely used in the treatment of cardiovascular diseases. WRKYs play important roles in plant metabolism, but their regulation mechanism in Salvia miltiorrhiza remains elusive. In this study, one WRKY transcription factor SmWRKY1 was isolated and functionally characterized from S. miltiorrhiza. Multiple sequence alignment and phylogenetic tree analysis showed SmWRKY1 shared high homology with other plant WRKYs such as CrWRKY1. SmWRKY1 was found predominantly expressed in leaves and stems, and was responsive to salicylic acid (SA, methyl jasmonate (MeJA, and nitric oxide (NO treatment. Subcellular localization analysis found that SmWRKY1 was localized in the nucleus. Over-expression of SmWRKY1 significantly elevated the transcripts of genes coding for enzymes in the MEP pathway especially 1-deoxy-D-xylulose-5-phosphate synthase (SmDXS and 1-deoxy-D-xylulose-5-phosphate reductoisomerase (SmDXR, resulted in over fivefold increase in tanshinones production in transgenic lines (up to 13.7 mg/g DW compared with the control lines. A dual-luciferase (Dual-LUC assay showed that SmWRKY1 can positively regulate SmDXR expression by binding to its promoter. Our work revealed that SmWRKY1 participated in the regulation of tanshinones biosynthesis and acted as a positive regulator through activating SmDXR in the MEP pathway, thus provided a new insight to further explore the regulation mechanism of tanshinones biosynthesis.

  15. Ubiquitin ligase RNF123 mediates degradation of heterochromatin protein 1α and β in lamin A/C knock-down cells.

    Directory of Open Access Journals (Sweden)

    Pankaj Chaturvedi

    Full Text Available The nuclear lamina is a key determinant of nuclear architecture, integrity and functionality in metazoan nuclei. Mutations in the human lamin A gene lead to highly debilitating genetic diseases termed as laminopathies. Expression of lamin A mutations or reduction in levels of endogenous A-type lamins leads to nuclear defects such as abnormal nuclear morphology and disorganization of heterochromatin. This is accompanied by increased proteasomal degradation of certain nuclear proteins such as emerin, nesprin-1α, retinoblastoma protein and heterochromatin protein 1 (HP1. However, the pathways of proteasomal degradation have not been well characterized.To investigate the mechanisms underlying the degradation of HP1 proteins upon lamin misexpression, we analyzed the effects of shRNA-mediated knock-down of lamins A and C in HeLa cells. Cells with reduced levels of expression of lamins A and C exhibited proteasomal degradation of HP1α and HP1β but not HP1γ. Since specific ubiquitin ligases are upregulated in lamin A/C knock-down cells, further studies were carried out with one of these ligases, RNF123, which has a putative HP1-binding motif. Ectopic expression of GFP-tagged RNF123 directly resulted in degradation of HP1α and HP1β. Mutational analysis showed that the canonical HP1-binding pentapeptide motif PXVXL in the N-terminus of RNF123 was required for binding to HP1 proteins and targeting them for degradation. The role of endogenous RNF123 in the degradation of HP1 isoforms was confirmed by RNF123 RNAi experiments. Furthermore, FRAP analysis suggested that HP1β was displaced from chromatin in laminopathic cells.Our data support a role for RNF123 ubiquitin ligase in the degradation of HP1α and HP1β upon lamin A/C knock-down. Hence lamin misexpression can cause degradation of mislocalized proteins involved in key nuclear processes by induction of specific components of the ubiquitin-proteasome system.

  16. Identifying Functional Neighborhoods within the Cell Nucleus: Proximity Analysis of Early S-Phase Replicating Chromatin Domains to Sites of Transcription, RNA Polymerase II, HP1γ, Matrin 3 and SAF-A

    Science.gov (United States)

    Malyavantham, Kishore S; Bhattacharya, Sambit; Barbeitos, Marcos; Mukherjee, Lopamudra; Xu, Jinhui; Fackelmayer, Frank O; Berezney, Ronald

    2009-01-01

    Higher order chromatin organization in concert with epigenetic regulation is a key process that determines gene expression at the global level. The organization of dynamic chromatin domains and their associated protein factors is intertwined with nuclear function to create higher levels of functional zones within the cell nucleus. As a step towards elucidating the organization and dynamics of these functional zones, we have investigated the spatial proximities among a constellation of functionally related sites that are found within euchromatic regions of the cell nucleus including: HP1γ, nascent transcript sites (TS), active DNA replicating sites in early S phase (PCNA) and RNA polymerase II sites. We report close associations among these different sites with proximity values specific for each combination. Analysis of matrin 3 and SAF-A sites demonstrates that these nuclear matrix proteins are highly proximal with the functionally related sites as well as to each other and display closely aligned and overlapping regions following application of the minimal spanning tree (MST) algorithm to visualize higher order network-like patterns. Our findings suggest that multiple factors within the nuclear microenvironment collectively form higher order combinatorial arrays of function. We propose a model for the organization of these functional neighborhoods which takes into account the proximity values of the individual sites and their spatial organization within the nuclear architecture. PMID:18618731

  17. The Weak Link HP-41C hand-held calculator program

    Science.gov (United States)

    Ross A. Phillips; Penn A. Peters; Gary D. Falk

    1982-01-01

    The Weak Link hand-held calculator program (HP-41C) quickly analyzes a system for logging production and costs. The production equations model conventional chain saw, skidder, loader, and tandemaxle truck operations in eastern mountain areas. Production of each function of the logging system may be determined so that the system may be balanced for minimum cost. The...

  18. Evaluation of personal dose equivalent 'HP(d)' in a external individual monitoring system for X and gamma radiation

    International Nuclear Information System (INIS)

    Santoro, C.; Antonio Filho, J.; Santos, M.A.P.

    2007-01-01

    The good of individual monitoring for external radiation is the assessment of occupational exposure from X and γ radiations in order to assure that the radiological conditions of the workplace are acceptable, safe and satisfactory. The evaluation of radiations doses for workers must not exceed dose limits specified for workers, according to national regulatory agencies. Nowadays, there are two external monitoring systems in use, both based on ICRU definitions. In the conventional system, the workers doses are evaluated in terms of Hx. The personal dosimeter is worn over chest surface and it is calibrated in function of air kerma. In the new system, the workers doses are evaluated in terms of HP(d) and the personal dosimeter is calibrated in function of phantom doses. The aim of this paper is to adapt an external dosimetry laboratory (based on photographic dosimetry) to evaluate the personal dosimeters in terms of HP(d). In this way, a simple methodology, based on linear programming, was utilized. In this adaptation, calibration curves were obtained for radiation qualities (W and N series) described by International Organization for Standardization (ISO 4037-1, 1995). These calibration curves offer a better accuracy on dose determinations and energy below 140 keV, improving the quality of service rendered the society. (author)

  19. Arabidopsis calcium-dependent protein kinase AtCPK1 plays a positive role in salt/drought-stress response.

    Science.gov (United States)

    Huang, Kui; Peng, Lu; Liu, Yingying; Yao, Rundong; Liu, Zhibin; Li, Xufeng; Yang, Yi; Wang, Jianmei

    2018-03-25

    The calcium-dependent protein kinases (CDPKs) play vital roles in plant response to various environmental stimuli. Here, we investigated the function of Arabidopsis AtCPK1 in response to salt and drought stress. The loss-of-function cpk1 mutant displayed hypersensitive to salt and drought stress, whereas overexpressing AtCPK1 in Arabidopsis plants significantly enhanced the resistance to salt or drought stress. The reduced or elevated tolerance of cpk1 mutant and AtCPK1-overexpressing lines was confirmed by the changes of proline, malondialdehyde (MDA) and H 2 O 2 . Real-time PCR analysis revealed that the expression of several stress-inducible genes (RD29A, COR15A, ZAT10, APX2) down-regulated in cpk1 mutant and up-regulated in AtCPK1-overexpressing plants. These results are likely to indicate that AtCPK1 positively regulates salt and drought stress in Arabidopsis. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Space and Time Adaptive Two-Mesh hp-Finite Element Method for Transient Microwave Heating Problems

    Czech Academy of Sciences Publication Activity Database

    Dubcová, Lenka; Šolín, Pavel; Červený, Jakub; Kůs, Pavel

    1-2, č. 30 (2010), s. 23-40 ISSN 0272-6343 R&D Projects: GA ČR(CZ) GA102/07/0496; GA AV ČR IAA100760702 Institutional research plan: CEZ:AV0Z20570509 Keywords : hp-finite element method * microwave heating * edge elements Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 0.844, year: 2010

  1. Comparative analysis of the folding dynamics and kinetics of an engineered knotted protein and its variants derived from HP0242 of Helicobacter pylori

    Science.gov (United States)

    Wang, Liang-Wei; Liu, Yu-Nan; Lyu, Ping-Chiang; Jackson, Sophie E.; Hsu, Shang-Te Danny

    2015-09-01

    Understanding the mechanism by which a polypeptide chain thread itself spontaneously to attain a knotted conformation has been a major challenge in the field of protein folding. HP0242 is a homodimeric protein from Helicobacter pylori with intertwined helices to form a unique pseudo-knotted folding topology. A tandem HP0242 repeat has been constructed to become the first engineered trefoil-knotted protein. Its small size renders it a model system for computational analyses to examine its folding and knotting pathways. Here we report a multi-parametric study on the folding stability and kinetics of a library of HP0242 variants, including the trefoil-knotted tandem HP0242 repeat, using far-UV circular dichroism and fluorescence spectroscopy. Equilibrium chemical denaturation of HP0242 variants shows the presence of highly populated dimeric and structurally heterogeneous folding intermediates. Such equilibrium folding intermediates retain significant amount of helical structures except those at the N- and C-terminal regions in the native structure. Stopped-flow fluorescence measurements of HP0242 variants show that spontaneous refolding into knotted structures can be achieved within seconds, which is several orders of magnitude faster than previously observed for other knotted proteins. Nevertheless, the complex chevron plots indicate that HP0242 variants are prone to misfold into kinetic traps, leading to severely rolled-over refolding arms. The experimental observations are in general agreement with the previously reported molecular dynamics simulations. Based on our results, kinetic folding pathways are proposed to qualitatively describe the complex folding processes of HP0242 variants.

  2. Preliminary assessment of Geant4 HP models and cross section libraries by reactor criticality benchmark calculations

    DEFF Research Database (Denmark)

    Cai, Xiao-Xiao; Llamas-Jansa, Isabel; Mullet, Steven

    2013-01-01

    Geant4 is an open source general purpose simulation toolkit for particle transportation in matter. Since the extension of the thermal scattering model in Geant4.9.5 and the availability of the IAEA HP model cross section libraries, it is now possible to extend the application area of Geant4......, U and O in uranium dioxide, Al metal, Be metal, and Fe metal. The native HP cross section library G4NDL does not include data for elements with atomic number larger than 92. Therefore, transuranic elements, which have impacts for a realistic reactor, can not be simulated by the combination of the HP...... models and the G4NDL library. However, cross sections of those missing isotopes were made available recently through the IAEA project “new evaluated neutron cross section libraries for Geant4”....

  3. Osr1 Interacts Synergistically with Wt1 to Regulate Kidney Organogenesis.

    Directory of Open Access Journals (Sweden)

    Jingyue Xu

    Full Text Available Renal hypoplasia is a common cause of pediatric renal failure and several adult-onset diseases. Recent studies have associated a variant of the OSR1 gene with reduction of newborn kidney size and function in heterozygotes and neonatal lethality with kidney defects in homozygotes. How OSR1 regulates kidney development and nephron endowment is not well understood, however. In this study, by using the recently developed CRISPR genome editing technology, we genetically labeled the endogenous Osr1 protein and show that Osr1 interacts with Wt1 in the developing kidney. Whereas mice heterozygous for either an Osr1 or Wt1 null allele have normal kidneys at birth, most mice heterozygous for both Osr1 and Wt1 exhibit defects in metanephric kidney development, including unilateral or bilateral kidney agenesis or hypoplasia. The developmental defects in the Osr1+/-Wt1+/- mouse embryos were detected as early as E10.5, during specification of the metanephric mesenchyme, with the Osr1+/-Wt1+/- mouse embryos exhibiting significantly reduced Pax2-positive and Six2-positive nephron progenitor cells. Moreover, expression of Gdnf, the major nephrogenic signal for inducing ureteric bud outgrowth, was significantly reduced in the metanephric mesenchyme in Osr1+/-Wt1+/- embryos in comparison with the Osr1+/- or Wt1+/- littermates. By E11.5, as the ureteric buds invade the metanephric mesenchyme and initiate branching morphogenesis, kidney morphogenesis was significantly impaired in the Osr1+/-Wt1+/- embryos in comparison with the Osr1+/- or Wt1+/- embryos. These results indicate that Osr1 and Wt1 act synergistically to regulate nephron endowment by controlling metanephric mesenchyme specification during early nephrogenesis.

  4. Type I NKT-cell-mediated TNF-α is a positive regulator of NLRP3 inflammasome priming.

    Science.gov (United States)

    Chow, Melvyn T; Duret, Helene; Andrews, Daniel M; Faveeuw, Christelle; Möller, Andreas; Smyth, Mark J; Paget, Christophe

    2014-07-01

    The NLRP3 inflammasome plays a crucial role in the innate immune response to pathogens and exogenous or endogenous danger signals. Its activity must be precisely and tightly regulated to generate tailored immune responses. However, the immune cell subsets and cytokines controlling NLRP3 inflammasome activity are still poorly understood. Here, we have shown a link between NKT-cell-mediated TNF-α and NLRP3 inflammasome activity. The NLRP3 inflammasome in APCs was critical to potentiate NKT-cell-mediated immune responses, since C57BL/6 NLRP3 inflammasome-deficient mice exhibited reduced responsiveness to α-galactosylceramide. Importantly, NKT cells were found to act as regulators of NLRP3 inflammasome signaling, as NKT-cell-derived TNF-α was required for optimal IL-1β and IL-18 production by myeloid cells in response to α-galactosylceramide, by acting on the NLRP3 inflammasome priming step. Thus, NKT cells play a role in the positive regulation of NLRP3 inflammasome priming by mediating the production of TNF-α, thus demonstrating another means by which NKT cells control early inflammation. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Assessment of four calculation methods proposed by the EC for waste hazardous property HP 14 'Ecotoxic'.

    Science.gov (United States)

    Hennebert, Pierre; Humez, Nicolas; Conche, Isabelle; Bishop, Ian; Rebischung, Flore

    2016-02-01

    Legislation published in December 2014 revised both the List of Waste (LoW) and amended Appendix III of the revised Waste Framework Directive 2008/98/EC; the latter redefined hazardous properties HP 1 to HP 13 and HP 15 but left the assessment of HP 14 unchanged to allow time for the Directorate General of the Environment of the European Commission to complete a study that is examining the impacts of four different calculation methods for the assessment of HP 14. This paper is a contribution to the assessment of the four calculation methods. It also includes the results of a fifth calculation method; referred to as "Method 2 with extended M-factors". Two sets of data were utilised in the assessment; the first (Data Set #1) comprised analytical data for 32 different waste streams (16 hazardous (H), 9 non-hazardous (NH) and 7 mirror entries, as classified by the LoW) while the second data set (Data Set #2), supplied by the eco industries, comprised analytical data for 88 waste streams, all classified as hazardous (H) by the LoW. Two approaches were used to assess the five calculation methods. The first approach assessed the relative ranking of the five calculation methods by the frequency of their classification of waste streams as H. The relative ranking of the five methods (from most severe to less severe) is: Method 3>Method 1>Method 2 with extended M-factors>Method 2>Method 4. This reflects the arithmetic ranking of the concentration limits of each method when assuming M=10, and is independent of the waste streams, or the H/NH/Mirror status of the waste streams. A second approach is the absolute matching or concordance with the LoW. The LoW is taken as a reference method and the H wastes are all supposed to be HP 14. This point is discussed in the paper. The concordance for one calculation method is established by the number of wastes with identical classification by the considered calculation method and the LoW (i.e. H to H, NH to NH). The discordance is

  6. CSR-1 RNAi pathway positively regulates histone expression in C. elegans.

    Science.gov (United States)

    Avgousti, Daphne C; Palani, Santhosh; Sherman, Yekaterina; Grishok, Alla

    2012-10-03

    Endogenous small interfering RNAs (endo-siRNAs) have been discovered in many organisms, including mammals. In C. elegans, depletion of germline-enriched endo-siRNAs found in complex with the CSR-1 Argonaute protein causes sterility and defects in chromosome segregation in early embryos. We discovered that knockdown of either csr-1, the RNA-dependent RNA polymerase (RdRP) ego-1, or the dicer-related helicase drh-3, leads to defects in histone mRNA processing, resulting in severe depletion of core histone proteins. The maturation of replication-dependent histone mRNAs, unlike that of other mRNAs, requires processing of their 3'UTRs through an endonucleolytic cleavage guided by the U7 snRNA, which is lacking in C. elegans. We found that CSR-1-bound antisense endo-siRNAs match histone mRNAs and mRNA precursors. Consistently, we demonstrate that CSR-1 directly binds to histone mRNA in an ego-1-dependent manner using biotinylated 2'-O-methyl RNA oligonucleotides. Moreover, we demonstrate that increasing the dosage of histone genes rescues the lethality associated with depletion of CSR-1 and EGO-1. These results support a positive and direct effect of RNAi on histone gene expression.

  7. Proposal of concentration limits for determining the hazard property HP 14 for waste using ecotoxicological tests.

    Science.gov (United States)

    Hennebert, Pierre

    2018-04-01

    substances), 37 were classified H (64%) and 21 were classified NH (36%). These concentration limits can be refined with the method proposed here, as soon as additional data of NH waste (by list and by composition) are available. The test battery (without options) and the concentration limits (in percent of waste in the culture/dilution medium) proposed are the following: A waste is hazardous for HP 14 'Ecotoxic' if the concentration of waste (eluate or solid) in the culture/dilution medium producing 50% of biological effect relative to the control EC 50 -30 min of Vibrio fischeri (EN ISO 11348-3) is lower than 15.8%, or if the EC 50 -72 h of Pseudokirchneriella subcapitata (EN ISO 8692) is lower than 7.03%, or if the EC 50 -48 h of Daphnia magna (EN ISO 6341) is lower than 7.95%, or if the EC 50 -6h of Arthrobacter globiformis (ISO 18187) is lower than 2.25%, or if the EC 50 -14d of Brassica rapa (EN ISO 11269-2) is lower than 13.7%, or if the EC 50 -48 h of Eisenia fetida avoidance test (ISO 17512-1) is lower than 3.75%. These CLs range between 2% and 16%, which is in line with the typically 10% concentration proposed without validation. To fix regulatory concentration limits, the regulators can use these CLs and the uncertainty of the ecotoxicological tests (standard deviation of inter-laboratory reproducibility typically of 25% of the mean, as published in the standards). Classification of waste for HP 14 with these tests and concentration limits will agree with the European List of Waste. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Cross-Validation of the Spanish HP-Version of the Jefferson Scale of Empathy Confirmed with Some Cross-Cultural Differences.

    Science.gov (United States)

    Alcorta-Garza, Adelina; San-Martín, Montserrat; Delgado-Bolton, Roberto; Soler-González, Jorge; Roig, Helena; Vivanco, Luis

    2016-01-01

    Medical educators agree that empathy is essential for physicians' professionalism. The Health Professional Version of the Jefferson Scale of Empathy (JSE-HP) was developed in response to a need for a psychometrically sound instrument to measure empathy in the context of patient care. Although extensive support for its validity and reliability is available, the authors recognize the necessity to examine psychometrics of the JSE-HP in different socio-cultural contexts to assure the psychometric soundness of this instrument. The first aim of this study was to confirm its psychometric properties in the cross-cultural context of Spain and Latin American countries. The second aim was to measure the influence of social and cultural factors on the development of medical empathy in health practitioners. The original English version of the JSE-HP was translated into International Spanish using back-translation procedures. The Spanish version of the JSE-HP was administered to 896 physicians from Spain and 13 Latin American countries. Data were subjected to exploratory factor analysis using principal component analysis (PCA) with oblique rotation (promax) to allow for correlation among the resulting factors, followed by a second analysis, using confirmatory factor analysis (CFA). Two theoretical models, one based on the English JSE-HP and another on the first Spanish student version of the JSE (JSE-S), were tested. Demographic variables were compared using group comparisons. A total of 715 (80%) surveys were returned fully completed. Cronbach's alpha coefficient of the JSE for the entire sample was 0.84. The psychometric properties of the Spanish JSE-HP matched those of the original English JSE-HP. However, the Spanish JSE-S model proved more appropriate than the original English model for the sample in this study. Group comparisons among physicians classified by gender, medical specialties, cultural and cross-cultural backgrounds yielded statistically significant differences

  9. Realidad aumentada en fisiología: descarga y breves instrucciones del uso de la aplicación HP REVEAL (AURASMA) sobre marcadores de nivel 1 y 2 en la docencia

    OpenAIRE

    Domínguez Vías, Germán; Carrasco Viñuela, Manuel; González Forero, David; Portillo Pacheco, Federico Luís; Vallo de Castro, Jose Juan

    2018-01-01

    Diálogo (Script): - Hola a todos. Una vez descargada la aplicación Aurasma, ahora llamada HP Reveal, tendréis que pulsar la aplicación, app AURASMA, y buscar y darle a seguir al grupo fisiologiaUCA. A continuación, podréis probar en clase activando el escáner y enfocando sobre marcadores de realidad aumentada de nivel 1, como código, o al final de este video marcadores de nivel 2, como son las fotos. Os saldrán, como estáis viendo, animaciones que os ayudarán a ver y comprender conceptos ...

  10. Structural effects at Λ3Hp-scattering

    International Nuclear Information System (INIS)

    Tartakovskij, V.K.; Fursaev, A.V.; Ivanova, O.I.

    2003-01-01

    In the paper the calculated dependences of falling hyper-tritons energy E=156 MeV differential cross sections from the scattering angle in the center of mass system θ and for more high energy values E from coupling energy ε 0 of Λ 3 H with regard to its disintegration into Λ-hyperon and deuteron are presented. It is established the strong dependence of differential cross section from ε 0 , moreover the sensitivity of differential cross sections to ε 0 value grows up with increasing of energy E. This allows to use the Λ 3 Hp-scattering as a method for ε 0 value elaboration

  11. Regulation of hedgehog signaling by Myc-interacting zinc finger protein 1, Miz1.

    Directory of Open Access Journals (Sweden)

    Jiuyi Lu

    Full Text Available Smoothened (Smo mediated Hedgehog (Hh signaling plays an essential role in regulating embryonic development and postnatal tissue homeostasis. Aberrant activation of the Hh pathway contributes to the formation and progression of various cancers. In vertebrates, however, key regulatory mechanisms responsible for transducing signals from Smo to the nucleus remain to be delineated. Here, we report the identification of Myc-interacting Zinc finger protein 1 (Miz1 as a Smo and Gli2 binding protein that positively regulates Hh signaling. Overexpression of Miz1 increases Gli luciferase reporter activity, whereas knockdown of endogenous Miz1 has the opposite effect. Activation of Smo induces translocation of Miz1 to the primary cilia together with Smo and Gli2. Furthermore, Miz1 is localized to the nucleus upon Hh activation in a Smo-dependent manner, and loss of Miz1 prevents the nuclear translocation of Gli2. More importantly, silencing Miz1 expression inhibits cell proliferation in vitro and the growth of Hh-driven medulloblastoma tumors allografted in SCID mice. Taken together, these results identify Miz1 as a novel regulator in the Hh pathway that plays an important role in mediating Smo-dependent oncogenic signaling.

  12. Improved Functional Properties and Efficiencies of Nitinol Wires Under High-Performance Shape Memory Effect (HP-SME)

    Science.gov (United States)

    Casati, R.; Saghafi, F.; Biffi, C. A.; Vedani, M.; Tuissi, A.

    2017-10-01

    Martensitic Ti-rich NiTi intermetallics are broadly used in various cyclic applications as actuators, which exploit the shape memory effect (SME). Recently, a new approach for exploiting austenitic Ni-rich NiTi shape memory alloys as actuators was proposed and named high-performance shape memory effect (HP-SME). HP-SME is based on thermal recovery of de-twinned martensite produced by mechanical loading of the parent phase. The aim of the manuscript consists in evaluating and comparing the fatigue and actuation properties of austenitic HP-SME wires and conventional martensitic SME wires. The effect of the thermomechanical cycling on the actuation response and the changes in the electrical resistivity of both shape memory materials were studied by performing the actuation tests at different stages of the fatigue life. Finally, the changes in the transition temperatures before and after cycling were also investigated by differential calorimetric tests.

  13. Financial Incentives Differentially Regulate Neural Processing of Positive and Negative Emotions during Value-Based Decision-Making

    Directory of Open Access Journals (Sweden)

    Anne M. Farrell

    2018-02-01

    Full Text Available Emotional and economic incentives often conflict in decision environments. To make economically desirable decisions then, deliberative neural processes must be engaged to regulate automatic emotional reactions. In this functional magnetic resonance imaging (fMRI study, we evaluated how fixed wage (FW incentives and performance-based (PB financial incentives, in which pay is proportional to outcome, differentially regulate positive and negative emotional reactions to hypothetical colleagues that conflicted with the economics of available alternatives. Neural activity from FW to PB incentive contexts decreased for positive emotional stimuli but increased for negative stimuli in middle temporal, insula, and medial prefrontal regions. In addition, PB incentives further induced greater responses to negative than positive emotional decisions in the frontal and anterior cingulate regions involved in emotion regulation. Greater response to positive than negative emotional features in these regions also correlated with lower frequencies of economically desirable choices. Our findings suggest that whereas positive emotion regulation involves a reduction of responses in valence representation regions, negative emotion regulation additionally engages brain regions for deliberative processing and signaling of incongruous events.

  14. Financial Incentives Differentially Regulate Neural Processing of Positive and Negative Emotions during Value-Based Decision-Making.

    Science.gov (United States)

    Farrell, Anne M; Goh, Joshua O S; White, Brian J

    2018-01-01

    Emotional and economic incentives often conflict in decision environments. To make economically desirable decisions then, deliberative neural processes must be engaged to regulate automatic emotional reactions. In this functional magnetic resonance imaging (fMRI) study, we evaluated how fixed wage (FW) incentives and performance-based (PB) financial incentives, in which pay is proportional to outcome, differentially regulate positive and negative emotional reactions to hypothetical colleagues that conflicted with the economics of available alternatives. Neural activity from FW to PB incentive contexts decreased for positive emotional stimuli but increased for negative stimuli in middle temporal, insula, and medial prefrontal regions. In addition, PB incentives further induced greater responses to negative than positive emotional decisions in the frontal and anterior cingulate regions involved in emotion regulation. Greater response to positive than negative emotional features in these regions also correlated with lower frequencies of economically desirable choices. Our findings suggest that whereas positive emotion regulation involves a reduction of responses in valence representation regions, negative emotion regulation additionally engages brain regions for deliberative processing and signaling of incongruous events.

  15. Hp Ge: Purification, crystal growth, and annealing properties

    International Nuclear Information System (INIS)

    Hall, R.N.

    1984-01-01

    The prospects for growing HP Ge crystals of increased size and purity are examined. One interesting approach is to grow dislocation-free crystals, which must then be annealed to reduce the concentration of V 2 H traps. The phenomena which occur during annealing are discussed and compared with experiment. Hydrogen, present in atomic form at the growth temperature, forms H 2 molecules during cooling, causing the effective diffusion coefficient to decrease rapidly. Models representing the reactions between H and the V 2 H, A(H, Si), and D(H,O) complexes are presented and analyzed

  16. The next step in coastal numerical models: spectral/hp element methods?

    DEFF Research Database (Denmark)

    Eskilsson, Claes; Engsig-Karup, Allan Peter; Sherwin, Spencer J.

    2005-01-01

    In this paper we outline the application of spectral/hp element methods for modelling nonlinear and dispersive waves. We present one- and two-dimensional test cases for the shallow water equations and Boussinesqtype equations – including highly dispersive Boussinesq-type equations....

  17. Mechanisms of continental subduction and exhumation of HP and UHP rocks

    NARCIS (Netherlands)

    Burov, Evgene; Francois, Thomas; Yamato, Philippe; Wolf, Sylvie

    We discuss possible scenarios of continental collision, and their relation to mechanisms of exhumation of HP and UHP rocks, inferred from thermo-mechanical numerical models accounting for thermo-rheological complexity of the continental lithosphere. Due to this complexity, mechanisms of continental

  18. Modeling of heterogeneous elastic materials by the multiscale hp-adaptive finite element method

    Science.gov (United States)

    Klimczak, Marek; Cecot, Witold

    2018-01-01

    We present an enhancement of the multiscale finite element method (MsFEM) by combining it with the hp-adaptive FEM. Such a discretization-based homogenization technique is a versatile tool for modeling heterogeneous materials with fast oscillating elasticity coefficients. No assumption on periodicity of the domain is required. In order to avoid direct, so-called overkill mesh computations, a coarse mesh with effective stiffness matrices is used and special shape functions are constructed to account for the local heterogeneities at the micro resolution. The automatic adaptivity (hp-type at the macro resolution and h-type at the micro resolution) increases efficiency of computation. In this paper details of the modified MsFEM are presented and a numerical test performed on a Fichera corner domain is presented in order to validate the proposed approach.

  19. VMP1 related autophagy and apoptosis in colorectal cancer cells: VMP1 regulates cell death

    Energy Technology Data Exchange (ETDEWEB)

    Qian, Qinyi [Department of Ultrasonograph, Changshu No. 2 People’s Hospital, Changshu (China); Zhou, Hao; Chen, Yan [Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou (China); Shen, Chenglong [Department of General Surgery, Changshu No. 2 People’s Hospital, Changshu (China); He, Songbing; Zhao, Hua; Wang, Liang [Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou (China); Wan, Daiwei, E-mail: 372710369@qq.com [Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou (China); Gu, Wen, E-mail: 505339704@qq.com [Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou (China)

    2014-01-17

    Highlights: •This research confirmed VMP1 as a regulator of autophagy in colorectal cancer cell lines. •We proved the pro-survival role of VMP1-mediated autophagy in colorectal cancer cell lines. •We found the interaction between VMP1 and BECLIN1 also existing in colorectal cancer cell lines. -- Abstract: Vacuole membrane protein 1 (VMP1) is an autophagy-related protein and identified as a key regulator of autophagy in recent years. In pancreatic cell lines, VMP1-dependent autophagy has been linked to positive regulation of apoptosis. However, there are no published reports on the role of VMP1 in autophagy and apoptosis in colorectal cancers. Therefore, to address this gap of knowledge, we decided to interrogate regulation of autophagy and apoptosis by VMP1. We have studied the induction of autophagy by starvation and rapamycin treatment in colorectal cell lines using electron microscopy, immunofluorescence, and immunoblotting. We found that starvation-induced autophagy correlated with an increase in VMP1 expression, that VMP1 interacted with BECLIN1, and that siRNA mediated down-regulation of VMP1-reduced autophagy. Next, we examined the relationship between VMP1-dependent autophagy and apoptosis and found that VMP1 down-regulation sensitizes cells to apoptosis and that agents that induce apoptosis down-regulate VMP1. In conclusion, similar to its reported role in other cell types, VMP1 is an important regulator of autophagy in colorectal cell lines. However, in contrast to its role in pancreatic cell lines, in colorectal cancer cells, VMP1-dependent autophagy appears to be pro-survival rather than pro-cell death.

  20. Surface adsorption of lattice HP proteins: Thermodynamics and structural transitions using Wang-Landau sampling

    International Nuclear Information System (INIS)

    Li Yingwai; Landau, David P; Wüst, Thomas

    2012-01-01

    Wang-Landau sampling has been applied to investigate the thermodynamics and structural properties of a lattice hydrophobic-polar heteropolymer (the HP protein model) interacting with an attractive substrate. For simplicity, we consider a short HP sequence consisting of only 36 monomers interacting with a substrate which attracts all monomers in the sequence. The conformational “phase transitions” have been identified by a canonical analysis of the specific heat and suitable structural observables. Three major “transitions”, namely, adsorption, hydrophobic core formation and “flattening” of adsorbed structures, are observed. Depending on the surface attractive strength relative to the intra-protein attraction among the H monomers, these processes take place in different sequences upon cooling.

  1. COAST code conversion from Cyber to HP

    International Nuclear Information System (INIS)

    Lee, Hae Cho

    1996-04-01

    The transient thermal hydraulic behavior of reactor coolant system in a nuclear power plant following loss of coolant flow is analyzed by use of COAST digital computer code. COAST calculates individual loop flow rates and steam generator pressure drops is a function of time following coast-down of any number of reactor coolant pumps. This report firstly describes detailed work carried out for installation of COAST on HP 9000/700 series and code validation results after installation. Secondly, a series of work is also describes in relation to installation of COAST on Apollo DN10000 series as well as relevant code validation results. Attached is a report on software verification and validation results. 7 refs. (Author) .new

  2. The tensor analyzing power T20 in the dd → 3Hen and dd → 3Hp reactions at the energies 140, 200 and 270 MeV and at zero degree

    International Nuclear Information System (INIS)

    Ladygin, V.P.; Uesaka, T.; Saito, T.

    2005-01-01

    The data on the tensor analyzing power T 20 in the dd → 3 Hen and dd → 3 Hp reactions at 140, 200 and 270 MeV of the deuteron kinetic energy and at zero degree obtained at RIKEN Accelerator Research Facility are presented. The observed positive sign of T 20 clearly demonstrates the sensitivity to the D/S wave ratios in the 3 He and 3 H in the energy domain of the measurements. The T 20 data for the 3 He-n and 3 H-p channels are in agreement within experimental accuracy

  3. Discrete frequency identification using the HP 5451B Fourier analyser

    International Nuclear Information System (INIS)

    Holland, L.; Barry, P.

    1977-01-01

    The frequency analysis by the HP5451B discrete frequency Fourier analyser is studied. The advantages of cross correlation analysis to identify discrete frequencies in a background noise are discussed in conjuction with the elimination of aliasing and wraparound error. Discrete frequency identification is illustrated by a series of graphs giving the results of analysing 'electrical' and 'acoustical' white noise and sinusoidal signals [pt

  4. PML-associated repressor of transcription (PAROT), a novel KRAB-zinc finger repressor, is regulated through association with PML nuclear bodies

    International Nuclear Information System (INIS)

    Fleischer, Sandra; Wiemann, Stefan; Will, Hans; Hofmann, Thomas G.

    2006-01-01

    Promyelocytic leukemia nuclear bodies (PML-NBs) are implicated in transcriptional regulation. Here we identify a novel transcriptional repressor, PML-associated repressor of transcription (PAROT), which is regulated in its repressor activity through recruitment to PML-NBs. PAROT is a Krueppel-associated box ( KRAB) zinc-finger (ZNF) protein, which comprises an amino terminal KRAB-A and KRAB-B box, a linker domain and 8 tandemly repeated C 2 H 2 -ZNF motifs at its carboxy terminus. Consistent with its domain structure, when tethered to DNA, PAROT represses transcription, and this is partially released by the HDAC inhibitor trichostatin A. PAROT colocalizes with members of the heterochromatin protein 1 (HP1) family and with transcriptional intermediary factor-1β/KRAB-associated protein 1 (TIF-1β/KAP1), a transcriptional corepressor for the KRAB-ZNF family. Interestingly, PML isoform IV, in contrast to PML-III, efficiently recruits PAROT and TIF-1β from heterochromatin to PML-NBs. PML-NB recruitment of PAROT partially releases its transcriptional repressor activity, indicating that PAROT can be regulated through subnuclear compartmentalization. Taken together, our data identify a novel transcriptional repressor and provide evidence for its regulation through association with PML-NBs

  5. The death-inducer obliterator 1 (Dido1) gene regulates embryonic stem cell self-renewal.

    Science.gov (United States)

    Liu, Yinyin; Kim, Hyeung; Liang, Jiancong; Lu, Weisi; Ouyang, Bin; Liu, Dan; Songyang, Zhou

    2014-02-21

    The regulatory network of factors that center on master transcription factors such as Oct4, Nanog, and Sox2 help maintain embryonic stem (ES) cells and ensure their pluripotency. The target genes of these master transcription factors define the ES cell transcriptional landscape. In this study, we report our findings that Dido1, a target of canonical transcription factors such as Oct4, Sox2, and Nanog, plays an important role in regulating ES cell maintenance. We found that depletion of Dido1 in mouse ES cells led to differentiation, and ectopic expression of Dido1 inhibited differentiation induced by leukemia inhibitory factor withdrawal. We further demonstrated that whereas Nanog and Oct4 could occupy the Dido1 locus and promote its transcription, Dido1 could also target to the loci of pluripotency factors such as Nanog and Oct4 and positively regulate their expression. Through this feedback and feedforward loop, Dido1 is able to regulate self-renewal of mouse ES cells.

  6. AICAR Protects against High Palmitate/High Insulin-Induced Intramyocellular Lipid Accumulation and Insulin Resistance in HL-1 Cardiac Cells by Inducing PPAR-Target Gene Expression

    Directory of Open Access Journals (Sweden)

    Ricardo Rodríguez-Calvo

    2015-01-01

    Full Text Available Here we studied the impact of 5-aminoimidazole-4-carboxamide riboside (AICAR, a well-known AMPK activator, on cardiac metabolic adaptation. AMPK activation by AICAR was confirmed by increased phospho-Thr172-AMPK and phospho-Ser79-ACC protein levels in HL-1 cardiomyocytes. Then, cells were exposed to AICAR stimulation for 24 h in the presence or absence of the AMPK inhibitor Compound C, and the mRNA levels of the three PPARs were analyzed by real-time RT-PCR. Treatment with AICAR induced gene expression of all three PPARs, but only the Ppara and Pparg regulation were dependent on AMPK. Next, we exposed HL-1 cells to high palmitate/high insulin (HP/HI conditions either in presence or in absence of AICAR, and we evaluated the expression of selected PPAR-targets genes. HP/HI induced insulin resistance and lipid storage was accompanied by increased Cd36, Acot1, and Ucp3 mRNA levels. AICAR treatment induced the expression of Acadvl and Glut4, which correlated to prevention of the HP/HI-induced intramyocellular lipid build-up, and attenuation of the HP/HI-induced impairment of glucose uptake. These data support the hypothesis that AICAR contributes to cardiac metabolic adaptation via regulation of transcriptional mechanisms.

  7. PULSION registered HP: Tunable, High Productivity Plasma Doping

    International Nuclear Information System (INIS)

    Felch, S. B.; Torregrosa, F.; Etienne, H.; Spiegel, Y.; Roux, L.; Turnbaugh, D.

    2011-01-01

    Plasma doping has been explored for many implant applications for over two decades and is now being used in semiconductor manufacturing for two applications: DRAM polysilicon counter-doping and contact doping. The PULSION HP is a new plasma doping tool developed by Ion Beam Services for high-volume production that enables customer control of the dominant mechanism--deposition, implant, or etch. The key features of this tool are a proprietary, remote RF plasma source that enables a high density plasma with low chamber pressure, resulting in a wide process space, and special chamber and wafer electrode designs that optimize doping uniformity.

  8. RBX2 maintains final retinal cell position in a DAB1-dependent and -independent fashion.

    Science.gov (United States)

    Fairchild, Corinne L; Hino, Keiko; Han, Jisoo S; Miltner, Adam M; Peinado Allina, Gabriel; Brown, Caileigh E; Burns, Marie E; La Torre, Anna; Simó, Sergi

    2018-02-02

    The laminated structure of the retina is fundamental for the organization of the synaptic circuitry that translates light input into patterns of action potentials. However, the molecular mechanisms underlying cell migration and layering of the retina are poorly understood. Here, we show that RBX2, a core component of the E3 ubiquitin ligase CRL5, is essential for retinal layering and function. RBX2 regulates the final cell position of rod bipolar cells, cone photoreceptors and Muller glia. Our data indicate that sustained RELN/DAB1 signaling, triggered by depletion of RBX2 or SOCS7 - a CRL5 substrate adaptor known to recruit DAB1 - causes rod bipolar cell misposition. Moreover, whereas SOCS7 also controls Muller glia cell lamination, it is not responsible for cone photoreceptor positioning, suggesting that RBX2, most likely through CRL5 activity, controls other signaling pathways required for proper cone localization. Furthermore, RBX2 depletion reduces the number of ribbon synapses and disrupts cone photoreceptor function. Together, these results uncover RBX2 as a crucial molecular regulator of retina morphogenesis and cone photoreceptor function. © 2018. Published by The Company of Biologists Ltd.

  9. LnqR, a TetR-family transcriptional regulator, positively regulates lacticin Q production in Lactococcus lactis QU 5.

    Science.gov (United States)

    Iwatani, Shun; Ishibashi, Naoki; Flores, Floirendo P; Zendo, Takeshi; Nakayama, Jiro; Sonomoto, Kenji

    2016-09-01

    Lacticin Q is an unmodified leaderless bacteriocin produced by Lactococcus lactis QU 5. It has been revealed that the production and self-immunity of lacticin Q are facilitated by a gene cluster lnqQBCDEF The gene for a putative TetR-family transcriptional regulator, termed lnqR, was found nearby the lnqQBCDEF cluster, but its involvement in lacticin Q biosynthesis remained unknown. In this study, we created an LnqR-overexpressing QU 5 recombinant by using lactococcal constitutive promoter P32 The recombinant QU 5 showed enhanced production of and self-immunity to lacticin Q. RT-PCR analysis has revealed that an overexpression of LnqR increases the amounts of lnqQBCDEF transcripts, and these six genes are transcribed as an operon in a single transcriptional unit. Interestingly, LnqR expression and thus lacticin Q production by L. lactis QU 5 was found temperature dependent, while LnzR, an LnqR-homologue, in L. lactis QU 14 was expressed in a similar but not identical manner to LnqR, resulting in dissimilar bacteriocin productivities by these strains. This report demonstrates LnqR as the first TetR-family transcriptional regulator involved in LAB bacteriocin biosynthesis and that, as an exceptional case of TetR-family regulators, LnqR positively regulates the transcription of these biosynthetic genes. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Forkhead Box C1 Regulates Human Primary Keratinocyte Terminal Differentiation.

    Directory of Open Access Journals (Sweden)

    Lianghua Bin

    Full Text Available The epidermis serves as a critical protective barrier between the internal and external environment of the human body. Its remarkable barrier function is established through the keratinocyte (KC terminal differentiation program. The transcription factors specifically regulating terminal differentiation remain largely unknown. Using a RNA-sequencing (RNA-seq profiling approach, we found that forkhead box c 1 (FOXC1 was significantly up-regulated in human normal primary KC during the course of differentiation. This observation was validated in human normal primary KC from several different donors and human skin biopsies. Silencing FOXC1 in human normal primary KC undergoing differentiation led to significant down-regulation of late terminal differentiation genes markers including epidermal differentiation complex genes, keratinization genes, sphingolipid/ceramide metabolic process genes and epidermal specific cell-cell adhesion genes. We further demonstrated that FOXC1 works down-stream of ZNF750 and KLF4, and upstream of GRHL3. Thus, this study defines FOXC1 as a regulator specific for KC terminal differentiation and establishes its potential position in the genetic regulatory network.

  11. Crystallography and Morphology of MC Carbides in Niobium-Titanium Modified As-Cast HP Alloys

    Science.gov (United States)

    Buchanan, Karl G.; Kral, Milo V.; Bishop, Catherine M.

    2014-07-01

    The microstructures of two as-cast heats of HP alloy stainless steels modified with niobium and titanium were examined with particular attention paid to the interdendritic niobium-titanium-rich carbides formed during solidification of these alloys. Generally, these precipitates obtain a blocky morphology in the as-cast condition. However, the (NbTi)C precipitates may obtain a nodular morphology. To provide further insight to the origin of the two different morphologies obtained by the (NbTi)C precipitates in the HP-NbTi alloy, the microstructure and crystallography of each have been studied in detail using scanning electron microscopy, transmission electron microscopy, various electron diffraction methods (EBSD, SAD, and CBED), and energy-dispersive X-ray spectroscopy.

  12. Nitric oxide acts as a positive regulator to induce metamorphosis of the ascidian Herdmania momus.

    Science.gov (United States)

    Ueda, Nobuo; Degnan, Sandie M

    2013-01-01

    Marine invertebrates commonly have a biphasic life cycle in which the metamorphic transition from a pelagic larva to a benthic post-larva is mediated by the nitric oxide signalling pathway. Nitric oxide (NO) is synthesised by nitric oxide synthase (NOS), which is a client protein of the molecular chaperon heat shock protein 90 (HSP90). It is notable, then, that both NO and HSP90 have been implicated in regulating metamorphosis in marine invertebrates as diverse as urochordates, echinoderms, molluscs, annelids, and crustaceans. Specifically, the suppression of NOS activity by the application of either NOS- or HSP90-inhibiting pharmacological agents has been shown consistently to induce the initiation of metamorphosis, leading to the hypothesis that a negative regulatory role of NO is widely conserved in biphasic life cycles. Further, the induction of metamorphosis by heat-shock has been demonstrated for multiple species. Here, we investigate the regulatory role of NO in induction of metamorphosis of the solitary tropical ascidian, Herdmania momus. By coupling pharmacological treatments with analysis of HmNOS and HmHSP90 gene expression, we present compelling evidence of a positive regulatory role for NO in metamorphosis of this species, in contrast to all existing ascidian data that supports the hypothesis of NO as a conserved negative regulator of metamorphosis. The exposure of competent H. momus larvae to a NOS inhibitor or an NO donor results in an up-regulation of NOS and HSP90 genes. Heat shock of competent larvae induces metamorphosis in a temperature dependent manner, up to a thermal tolerance that approaches 35°C. Both larval/post-larval survival and the appearance of abnormal morphologies in H. momus post-larvae reflect the magnitude of up-regulation of the HSP90 gene in response to heat-shock. The demonstrated role of NO as a positive metamorphic regulator in H. momus suggests the existence of inter-specific adaptations of NO regulation in ascidian

  13. Negative regulation of NOD1 mediated angiogenesis by PPARγ-regulated miR-125a

    International Nuclear Information System (INIS)

    Kang, Hyesoo; Park, Youngsook; Lee, Aram; Seo, Hyemin; Kim, Min Jung; Choi, Jihea; Jo, Ha-neul; Jeong, Ha-neul; Cho, Jin Gu; Chang, Woochul; Lee, Myeong-Sok; Jeon, Raok; Kim, Jongmin

    2017-01-01

    Infection with pathogens activates the endothelial cell and its sustained activation may result in impaired endothelial function. Endothelial dysfunction contributes to the pathologic angiogenesis that is characteristic of infection-induced inflammatory pathway activation. Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is a protein receptor which recognizes bacterial molecules and stimulates an immune reaction in various cells; however, the underlying molecular mechanisms in the regulation of inflammation-triggered angiogenesis are not fully understood. Here we report that peroxisome proliferator-activated receptor gamma (PPARγ)-mediated miR-125a serves as an important regulator of NOD1 agonist-mediated angiogenesis in endothelial cells by directly targeting NOD1. Treatment of human umbilical vein endothelial cells with natural PPARγ ligand, 15-Deoxy-Delta12,14-prostaglandin J2, led to inhibition of NOD1 expression; contrarily, protein levels of NOD1 were significantly increased by PPARγ knockdown. We report that PPARγ regulation of NOD1 expression is a novel microRNA-mediated regulation in endothelial cells. MiR-125a expression was markedly decreased in human umbilical vein endothelial cells subjected to PPARγ knockdown while 15-Deoxy-Delta12,14-prostaglandin J2 treatment increased the level of miR-125a. In addition, NOD1 is closely regulated by miR-125a, which directly targets the 3′ untranslated region of NOD1. Moreover, both overexpression of miR-125a and PPARγ activation led to inhibition of NOD1 agonist-induced tube formation in endothelial cells. Finally, NOD1 agonist increased the formation of cranial and subintestinal vessel plexus in zebrafish, and this effect was abrogated by concurrent PPARγ activation. Overall, these findings identify a PPARγ-miR-125a-NOD1 signaling axis in endothelial cells that is critical in the regulation of inflammation-mediated angiogenesis. - Highlights: • Expression of NOD1 is regulated by

  14. GBF1 differentially regulates CAT2 and PAD4 transcription to promote pathogen defense in Arabidopsis thaliana.

    Science.gov (United States)

    Giri, Mrunmay K; Singh, Nidhi; Banday, Zeeshan Z; Singh, Vijayata; Ram, Hathi; Singh, Deepjyoti; Chattopadhyay, Sudip; Nandi, Ashis K

    2017-09-01

    G-BOX BINDING FACTOR 1 (GBF1) influences light-regulated seedling development in Arabidopsis, and inhibits CATALASE 2 (CAT2) expression during senescence. CAT2 functions as a scavenger of hydrogen peroxide. The role of GBF1 in the defense response is not known. We report here that GBF1 positively influences the defense against virulent and avirulent strains of Pseudomonas syringae. The gbf1 mutants are susceptible, whereas GBF1 over-expresser transgenic plants are resistant to bacterial pathogens. GBF1 negatively regulates pathogen-induced CAT2 expression and thereby positively regulates the hypersensitive response. In addition to CAT2 promoter, GBF1 binds to the G-box-like element present in the intron of PHYTOALEXIN DEFICIENT 4 (PAD4). This association of GBF1 with PAD4 intron is enhanced upon pathogenesis. GBF1 positively regulates PAD4 transcription in an intron-dependent manner. GBF1-mediated positive regulation of PAD4 expression is also evident in gbf1 mutant and GBF1 over-expression lines. Similar to pad4 mutants, pathogen-induced camalexin and salicylic acid (SA) accumulation, and expression of SA-inducible PATHOGENESIS RELATED1 (PR1) gene are compromised in the gbf1 mutant. Exogenous application of SA rescues the loss-of-defense phenotypes of gbf1 mutant. Thus, altogether, our results demonstrate that GBF1 is an important component of the plant defense response that functions upstream of SA accumulation and, by oppositely regulating CAT2 and PAD4, promotes disease resistance in Arabidopsis. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  15. Prediction of extracellular proteases of the human pathogen Helicobacter pylori reveals proteolytic activity of the Hp1018/19 protein HtrA.

    Directory of Open Access Journals (Sweden)

    Martin Löwer

    Full Text Available Exported proteases of Helicobacter pylori (H. pylori are potentially involved in pathogen-associated disorders leading to gastric inflammation and neoplasia. By comprehensive sequence screening of the H. pylori proteome for predicted secreted proteases, we retrieved several candidate genes. We detected caseinolytic activities of several such proteases, which are released independently from the H. pylori type IV secretion system encoded by the cag pathogenicity island (cagPAI. Among these, we found the predicted serine protease HtrA (Hp1019, which was previously identified in the bacterial secretome of H. pylori. Importantly, we further found that the H. pylori genes hp1018 and hp1019 represent a single gene likely coding for an exported protein. Here, we directly verified proteolytic activity of HtrA in vitro and identified the HtrA protease in zymograms by mass spectrometry. Overexpressed and purified HtrA exhibited pronounced proteolytic activity, which is inactivated after mutation of Ser205 to alanine in the predicted active center of HtrA. These data demonstrate that H. pylori secretes HtrA as an active protease, which might represent a novel candidate target for therapeutic intervention strategies.

  16. SGN III code conversion from Apollo to HP

    International Nuclear Information System (INIS)

    Lee, Hae Cho

    1996-04-01

    SGN III computer code is used to analyze transient behavior of reactor coolant system, pressurizer and steam generators in the event of main steam line break (MSLB), and to calculate mass and energy release for containment design. This report firstly describes detailed work carried out for installation of SFN III on Apollo DN 10000 and code validation results after installation. Secondly, a series of work is also describes in relation to installation of SGN III on HP 9000/700 series as well as relevant code validation results. Attached is a report on software verification and validation results. 8 refs. (Author) .new

  17. CONTRANS 2 code conversion from Apollo to HP

    International Nuclear Information System (INIS)

    Lee, Hae Cho

    1996-01-01

    CONTRANS2 computer code is used to calculate transient thermal hydraulic responses of containment building to loss of coolant and main steam line break accident. Mass and energy release to the containment following an accident are code inputs. This report firstly describes detailed work carried out for installation of CONTRANS2 on Apollo DN10000 and code validation results after installation. Secondly, A series of work is also describes in relation to installation of CONTRANS2 on HP 9000/700 series as well as relevant code validation results. Attached is a report on software verification and validation results. 7 refs. (Author) .new

  18. The cag PAI is intact and functional but HP0521 varies significantly in Helicobacter pylori isolates from Malaysia and Singapore.

    Science.gov (United States)

    Schmidt, H-M A; Andres, S; Nilsson, C; Kovach, Z; Kaakoush, N O; Engstrand, L; Goh, K-L; Fock, K M; Forman, D; Mitchell, H

    2010-04-01

    Helicobacter pylori-related disease is at least partially attributable to the genotype of the infecting strain, particularly the presence of specific virulence factors. We investigated the prevalence of a novel combination of H. pylori virulence factors, including the cag pathogenicity island (PAI), and their association with severe disease in isolates from the three major ethnicities in Malaysia and Singapore, and evaluated whether the cag PAI was intact and functional in vitro. Polymerase chain reaction (PCR) was used to detect dupA, cagA, cagE, cagT, cagL and babA, and to type vacA, the EPIYA motifs, HP0521 alleles and oipA ON status in 159 H. pylori clinical isolates. Twenty-two strains were investigated for IL-8 induction and CagA translocation in vitro. The prevalence of cagA, cagE, cagL, cagT, babA, oipA ON and vacA s1 and i1 was >85%, irrespective of the disease state or ethnicity. The prevalence of dupA and the predominant HP0521 allele and EPIYA motif varied significantly with ethnicity (p < 0.05). A high prevalence of an intact cag PAI was found in all ethnic groups; however, no association was observed between any virulence factor and disease state. The novel association between the HP0521 alleles, EPIYA motifs and host ethnicity indicates that further studies to determine the function of this gene are important.

  19. Histone variant H2A.Z antagonizes the positive effect of the transcriptional activator CPC1 to regulate catalase-3 expression under normal and oxidative stress conditions.

    Science.gov (United States)

    Dong, Qing; Wang, Yajun; Qi, Shaohua; Gai, Kexin; He, Qun; Wang, Ying

    2018-05-05

    In eukaryotes, deposition of the histone variant H2A.Z into nucleosomes through the chromatin remodeling complex, SWR1, is a crucial step in modulating gene transcription. Recently, H2A.Z has been shown to control the expression of responsive genes, but the underlying mechanism of how H2A.Z responds to physiological stimuli is not well understood. Here, we reveal that, in Neurospora crassa, H2A.Z is a negative regulator of catalase-3 gene, which is responsible for resistance to oxidative stress. H2A.Z represses cat-3 gene expression through direct incorporation at cat-3 locus in a SWR1 complex dependent pathway. Notably, loss of H2A.Z or SWR1 subunits leads to increased binding of a transcription factor, CPC1, at cat-3 locus. Additionally, introduction of plasmids containing gene encoding H2A.Z or SWR1 complex subunits into wild-type strains decreased CAT-3 expression, indicating that H2A.Z counteracts the positive effect of CPC1 to achieve low level cat-3 expression under non-inductive condition. Furthermore, upon oxidative stress, H2A.Z is rapidly evicted from cat-3 locus for the recruitment of CPC1, resulting in robust and full cat-3 gene expression in response to external stimuli. Collectively, this study strongly demonstrates that H2A.Z antagonizes the function of transcription factor to regulate responsive gene transcription under normal conditions and to poise for gene full activation under oxidative stress. Copyright © 2018. Published by Elsevier Inc.

  20. Cross-validation of the Spanish HP-Version of the Jefferson Scale of Empathy confirmed with some cross-cultural differences

    Directory of Open Access Journals (Sweden)

    Adelina Alcorta-Garza

    2016-07-01

    Full Text Available Context: Medical educators agree that empathy is essential for physicians’ professionalism. The Health Professional Version of the Jefferson Scale of Empathy (JSE-HP was developed in response to a need for a psychometrically sound instrument to measure empathy in the context of patient care. Although extensive support for its validity and reliability is available, the authors recognize the necessity to examine psychometrics of the JSE-HP in different socio-cultural contexts to assure the psychometric soundness of this instrument. The first aim of this study was to confirm its psychometric properties in the cross-cultural context of Spain and Latin American countries. The second aim was to measure the influence of social and cultural factors on the development of medical empathy in health practitioners.Methods: The original English version of the JSE-HP was translated into International Spanish using back-translation procedures. The Spanish version of the JSE-HP was administered to 896 physicians from Spain and thirteen Latin American countries. Data were subjected to exploratory factor analysis using principal component analysis with oblique rotation (promax to allow for correlation among the resulting factors, followed by a second analysis, using confirmatory factor analysis. Two theoretical models, one based on the English JSE-HP and another on the first Spanish student version of the JSE (JSE-S, were tested. Demographic variables were compared using group comparisons.Results: A total of 715 (80% surveys were returned fully completed. Cronbach’s alpha coefficient of the JSE for the entire sample was 0.84. The psychometric properties of the Spanish JSE-HP matched those of the original English JSE-HP. However, the Spanish JSE-S model proved more appropriate than the original English model for the sample in this study. Group comparisons among physicians classified by gender, medical specialties, cultural and cross-cultural backgrounds yielded

  1. Frizzled 7 expression is positively regulated by SIRT1 and β-catenin in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Glenn E Simmons

    Full Text Available The Wnt signaling pathway is often chronically activated in diverse human tumors, and the Frizzled (FZD family of receptors for Wnt ligands, are central to propagating oncogenic signals in a β-catenin-dependent and independent manner. SIRT1 is a class III histone deacetylase (HDAC that deacetylates histone and non-histone proteins to regulate gene transcription and protein function. We previously demonstrated that SIRT1 loss of function led to a significant decrease in the levels of Dishevelled (Dvl proteins. To further explore this connection between the sirtuins and components of the Wnt pathway, we analyzed sirtuin-mediated regulation of FZD proteins. Here we explore the contribution of sirtuin deacetylases in promoting constitutive Wnt pathway activation in breast cancer cells. We demonstrate that the use of small molecule inhibitors of SIRT1 and SIRT2, and siRNA specific to SIRT1, all reduce the levels of FZD7 mRNA. We further demonstrate that pharmacologic inhibition of SIRT1/2 causes a marked reduction in FZD7 protein levels. Additionally, we show that β-catenin and c-Jun occupy the 7 kb region upstream of the transcription start site of the FZD7 gene, and SIRT1 inhibition leads to a reduction in the occupancy of both β-catenin and c-Jun at points along this region. This work uncovers a new mechanism for the regulation of FZD7 and provides a critical new link between the sirtuins and FZD7, one of the earliest nodal points from which oncogenic Wnt signaling emanates. This study shows that inhibition of specific sirtuins may provide a unique strategy for inhibiting the constitutively active Wnt pathway at the level of the receptor.

  2. Interleukin-1β: A New Regulator of the Kynurenine Pathway Affecting Human Hippocampal Neurogenesis

    Science.gov (United States)

    Zunszain, Patricia A; Anacker, Christoph; Cattaneo, Annamaria; Choudhury, Shanas; Musaelyan, Ksenia; Myint, Aye Mu; Thuret, Sandrine; Price, Jack; Pariante, Carmine M

    2012-01-01

    Increased inflammation and reduced neurogenesis have been associated with the pathophysiology of major depression. Here, we show for the first time how IL-1β, a pro-inflammatory cytokine shown to be increased in depressed patients, decreases neurogenesis in human hippocampal progenitor cells. IL-1β was detrimental to neurogenesis, as shown by a decrease in the number of doublecortin-positive neuroblasts (−28%), and mature, microtubule-associated protein-2-positive neurons (−36%). Analysis of the enzymes that regulate the kynurenine pathway showed that IL-1β induced an upregulation of transcripts for indolamine-2,3-dioxygenase (IDO), kynurenine 3-monooxygenase (KMO), and kynureninase (42-, 12- and 30-fold increase, respectively, under differentiating conditions), the enzymes involved in the neurotoxic arm of the kynurenine pathway. Moreover, treatment with IL-1β resulted in an increase in kynurenine, the catabolic product of IDO-induced tryptophan metabolism. Interestingly, co-treatment with the KMO inhibitor Ro 61-8048 reversed the detrimental effects of IL-1β on neurogenesis. These observations indicate that IL-1β has a critical role in regulating neurogenesis whereas affecting the availability of tryptophan and the production of enzymes conducive to toxic metabolites. Our results suggest that inhibition of the kynurenine pathway may provide a new therapy to revert inflammatory-induced reduction in neurogenesis. PMID:22071871

  3. The Nesprin family member ANC-1 regulates synapse formation and axon termination by functioning in a pathway with RPM-1 and β-Catenin.

    Science.gov (United States)

    Tulgren, Erik D; Turgeon, Shane M; Opperman, Karla J; Grill, Brock

    2014-07-01

    Mutations in Nesprin-1 and 2 (also called Syne-1 and 2) are associated with numerous diseases including autism, cerebellar ataxia, cancer, and Emery-Dreifuss muscular dystrophy. Nesprin-1 and 2 have conserved orthologs in flies and worms called MSP-300 and abnormal nuclear Anchorage 1 (ANC-1), respectively. The Nesprin protein family mediates nuclear and organelle anchorage and positioning. In the nervous system, the only known function of Nesprin-1 and 2 is in regulation of neurogenesis and neural migration. It remains unclear if Nesprin-1 and 2 regulate other functions in neurons. Using a proteomic approach in C. elegans, we have found that ANC-1 binds to the Regulator of Presynaptic Morphology 1 (RPM-1). RPM-1 is part of a conserved family of signaling molecules called Pam/Highwire/RPM-1 (PHR) proteins that are important regulators of neuronal development. We have found that ANC-1, like RPM-1, regulates axon termination and synapse formation. Our genetic analysis indicates that ANC-1 functions via the β-catenin BAR-1, and the ANC-1/BAR-1 pathway functions cell autonomously, downstream of RPM-1 to regulate neuronal development. Further, ANC-1 binding to the nucleus is required for its function in axon termination and synapse formation. We identify variable roles for four different Wnts (LIN-44, EGL-20, CWN-1 and CWN-2) that function through BAR-1 to regulate axon termination. Our study highlights an emerging, broad role for ANC-1 in neuronal development, and unveils a new and unexpected mechanism by which RPM-1 functions.

  4. Quantifying Net Synergy/Redundancy of Spontaneous Variability Regulation via Predictability and Transfer Entropy Decomposition Frameworks.

    Science.gov (United States)

    Porta, Alberto; Bari, Vlasta; De Maria, Beatrice; Takahashi, Anielle C M; Guzzetti, Stefano; Colombo, Riccardo; Catai, Aparecida M; Raimondi, Ferdinando; Faes, Luca

    2017-11-01

    Objective: Indexes assessing the balance between redundancy and synergy were hypothesized to be helpful in characterizing cardiovascular control from spontaneous beat-to-beat variations of heart period (HP), systolic arterial pressure (SAP), and respiration (R). Methods: Net redundancy/synergy indexes were derived according to predictability and transfer entropy decomposition strategies via a multivariate linear regression approach. Indexes were tested in two protocols inducing modifications of the cardiovascular regulation via baroreflex loading/unloading (i.e., head-down tilt at -25° and graded head-up tilt at 15°, 30°, 45°, 60°, 75°, and 90°, respectively). The net redundancy/synergy of SAP and R to HP and of HP and R to SAP were estimated over stationary sequences of 256 successive values. Results: We found that: 1) regardless of the target (i.e., HP or SAP) redundancy was prevalent over synergy and this prevalence was independent of type and magnitude of the baroreflex challenge; 2) the prevalence of redundancy disappeared when decoupling inputs from output via a surrogate approach; 3) net redundancy was under autonomic control given that it varied in proportion to the vagal withdrawal during graded head-up tilt; and 4) conclusions held regardless of the decomposition strategy. Conclusion: Net redundancy indexes can monitor changes of cardiovascular control from a perspective completely different from that provided by more traditional univariate and multivariate methods. Significance: Net redundancy measures might provide a practical tool to quantify the reservoir of effective cardiovascular regulatory mechanisms sharing causal influences over a target variable. Objective: Indexes assessing the balance between redundancy and synergy were hypothesized to be helpful in characterizing cardiovascular control from spontaneous beat-to-beat variations of heart period (HP), systolic arterial pressure (SAP), and respiration (R). Methods: Net redundancy

  5. DNA demethylases target promoter transposable elements to positively regulate stress responsive genes in Arabidopsis.

    Science.gov (United States)

    Le, Tuan-Ngoc; Schumann, Ulrike; Smith, Neil A; Tiwari, Sameer; Au, Phil Chi Khang; Zhu, Qian-Hao; Taylor, Jennifer M; Kazan, Kemal; Llewellyn, Danny J; Zhang, Ren; Dennis, Elizabeth S; Wang, Ming-Bo

    2014-09-17

    DNA demethylases regulate DNA methylation levels in eukaryotes. Arabidopsis encodes four DNA demethylases, DEMETER (DME), REPRESSOR OF SILENCING 1 (ROS1), DEMETER-LIKE 2 (DML2), and DML3. While DME is involved in maternal specific gene expression during seed development, the biological function of the remaining DNA demethylases remains unclear. We show that ROS1, DML2, and DML3 play a role in fungal disease resistance in Arabidopsis. A triple DNA demethylase mutant, rdd (ros1 dml2 dml3), shows increased susceptibility to the fungal pathogen Fusarium oxysporum. We identify 348 genes differentially expressed in rdd relative to wild type, and a significant proportion of these genes are downregulated in rdd and have functions in stress response, suggesting that DNA demethylases maintain or positively regulate the expression of stress response genes required for F. oxysporum resistance. The rdd-downregulated stress response genes are enriched for short transposable element sequences in their promoters. Many of these transposable elements and their surrounding sequences show localized DNA methylation changes in rdd, and a general reduction in CHH methylation, suggesting that RNA-directed DNA methylation (RdDM), responsible for CHH methylation, may participate in DNA demethylase-mediated regulation of stress response genes. Many of the rdd-downregulated stress response genes are downregulated in the RdDM mutants nrpd1 and nrpe1, and the RdDM mutants nrpe1 and ago4 show enhanced susceptibility to F. oxysporum infection. Our results suggest that a primary function of DNA demethylases in plants is to regulate the expression of stress response genes by targeting promoter transposable element sequences.

  6. Mit1 Transcription Factor Mediates Methanol Signaling and Regulates the Alcohol Oxidase 1 (AOX1) Promoter in Pichia pastoris*

    Science.gov (United States)

    Wang, Xiaolong; Wang, Qi; Wang, Jinjia; Bai, Peng; Shi, Lei; Shen, Wei; Zhou, Mian; Zhou, Xiangshan; Zhang, Yuanxing; Cai, Menghao

    2016-01-01

    The alcohol oxidase 1 (AOX1) promoter (PAOX1) of Pichia pastoris is the most powerful and commonly used promoter for driving protein expression. However, mechanisms regulating its transcriptional activity are unclear. Here, we identified a Zn(II)2Cys6-type methanol-induced transcription factor 1 (Mit1) and elucidated its roles in regulating PAOX1 activity in response to glycerol and methanol. Mit1 regulated the expression of many genes involved in methanol utilization pathway, including AOX1, but did not participate in peroxisome proliferation and transportation of peroxisomal proteins during methanol metabolism. Structural analysis of Mit1 by performing domain deletions confirmed its specific and critical role in the strict repression of PAOX1 in glycerol medium. Importantly, Mit1, Mxr1, and Prm1, which positively regulated PAOX1 in response to methanol, were bound to PAOX1 at different sites and did not interact with each other. However, these factors cooperatively activated PAOX1 through a cascade. Mxr1 mainly functioned during carbon derepression, whereas Mit1 and Prm1 functioned during methanol induction, with Prm1 transmitting methanol signal to Mit1 by binding to the MIT1 promoter (PMIT1), thus increasingly expressing Mit1 and subsequently activating PAOX1. PMID:26828066

  7. On Adjusting the H-P Filter for the Frequency of Observations

    NARCIS (Netherlands)

    Uhlig, H.F.H.V.S.; Ravn, M.

    1997-01-01

    This paper studies how the HP-Filter should be adjusted, when changing the frequency of observations. The usual choices in the literature are to adjust the smoothing parameter by multiplying it with either the square of the observation frequency ratios or simply with the observation frequency. In

  8. The C-terminal domain of Nrf1 negatively regulates the full-length CNC-bZIP factor and its shorter isoform LCR-F1/Nrf1β; both are also inhibited by the small dominant-negative Nrf1γ/δ isoforms that down-regulate ARE-battery gene expression.

    Science.gov (United States)

    Zhang, Yiguo; Qiu, Lu; Li, Shaojun; Xiang, Yuancai; Chen, Jiayu; Ren, Yonggang

    2014-01-01

    The C-terminal domain (CTD, aa 686-741) of nuclear factor-erythroid 2 p45-related factor 1 (Nrf1) shares 53% amino acid sequence identity with the equivalent Neh3 domain of Nrf2, a homologous transcription factor. The Neh3 positively regulates Nrf2, but whether the Neh3-like (Neh3L) CTD of Nrf1 has a similar role in regulating Nrf1-target gene expression is unknown. Herein, we report that CTD negatively regulates the full-length Nrf1 (i.e. 120-kDa glycoprotein and 95-kDa deglycoprotein) and its shorter isoform LCR-F1/Nrf1β (55-kDa). Attachment of its CTD-adjoining 112-aa to the C-terminus of Nrf2 yields the chimaeric Nrf2-C112Nrf1 factor with a markedly decreased activity. Live-cell imaging of GFP-CTD reveals that the extra-nuclear portion of the fusion protein is allowed to associate with the endoplasmic reticulum (ER) membrane through the amphipathic Neh3L region of Nrf1 and its basic c-tail. Thus removal of either the entire CTD or the essential Neh3L portion within CTD from Nrf1, LCR-F1/Nrf1β and Nrf2-C112Nrf1, results in an increase in their transcriptional ability to regulate antioxidant response element (ARE)-driven reporter genes. Further examinations unravel that two smaller isoforms, 36-kDa Nrf1γ and 25-kDa Nrf1δ, act as dominant-negative inhibitors to compete against Nrf1, LCR-F1/Nrf1β and Nrf2. Relative to Nrf1, LCR-F1/Nrf1β is a weak activator, that is positively regulated by its Asn/Ser/Thr-rich (NST) domain and acidic domain 2 (AD2). Like AD1 of Nrf1, both AD2 and NST domain of LCR-F1/Nrf1β fused within two different chimaeric contexts to yield Gal4D:Nrf1β607 and Nrf1β:C270Nrf2, positively regulate their transactivation activity of cognate Gal4- and Nrf2-target reporter genes. More importantly, differential expression of endogenous ARE-battery genes is attributable to up-regulation by Nrf1 and LCR-F1/Nrf1β and down-regulation by Nrf1γ and Nrf1δ.

  9. SALT-RESPONSIVE ERF1 is a negative regulator of grain filling and gibberellin-mediated seedling establishment in rice.

    Science.gov (United States)

    Schmidt, Romy; Schippers, Jos H M; Mieulet, Delphine; Watanabe, Mutsumi; Hoefgen, Rainer; Guiderdoni, Emmanuel; Mueller-Roeber, Bernd

    2014-02-01

    Grain quality is an important agricultural trait that is mainly determined by grain size and composition. Here, we characterize the role of the rice transcription factor (TF) SALT-RESPONSIVE ERF1 (SERF1) during grain development. Through genome-wide expression profiling and chromatin immunoprecipitation, we found that SERF1 directly regulates RICE PROLAMIN-BOX BINDING FACTOR (RPBF), a TF that functions as a positive regulator of grain filling. Loss of SERF1 enhances RPBF expression resulting in larger grains with increased starch content, while SERF1 overexpression represses RPBF resulting in smaller grains. Consistently, during grain filling, starch biosynthesis genes such as GRANULE-BOUND STARCH SYNTHASEI (GBSSI), STARCH SYNTHASEI (SSI), SSIIIa, and ADP-GLUCOSE PYROPHOSPHORYLASE LARGE SUBUNIT2 (AGPL2) are up-regulated in SERF1 knockout grains. Moreover, SERF1 is a direct upstream regulator of GBSSI. In addition, SERF1 negatively regulates germination by controlling RPBF expression, which mediates the gibberellic acid (GA)-induced expression of RICE AMYLASE1A (RAmy1A). Loss of SERF1 results in more rapid seedling establishment, while SERF1 overexpression has the opposite effect. Our study reveals that SERF1 represents a negative regulator of grain filling and seedling establishment by timing the expression of RPBF.

  10. Interferon Potentiates Toll-Like Receptor-Induced Prostaglandin D2 Production through Positive Feedback Regulation between Signal Transducer and Activators of Transcription 1 and Reactive Oxygen Species

    Directory of Open Access Journals (Sweden)

    Ji-Yun Kim

    2017-12-01

    Full Text Available Prostaglandin D2 (PGD2 is a potent lipid mediator that controls inflammation, and its dysregulation has been implicated in diverse inflammatory disorders. Despite significant progress made in understanding the role of PGD2 as a key regulator of immune responses, the molecular mechanism underlying PGD2 production remains unclear, particularly upon challenge with different and multiple inflammatory stimuli. Interferons (IFNs potentiate macrophage activation and act in concert with exogenous inflammatory mediators such as toll-like receptor (TLR ligands to amplify inflammatory responses. A recent study found that IFN-γ enhanced lipopolysaccharide-induced PGD2 production, indicating a role of IFNs in PGD2 regulation. Here, we demonstrate that TLR-induced PGD2 production by macrophages was significantly potentiated by signaling common to IFN-β and IFN-γ in a signal transducer and activators of transcription (STAT1-dependent mechanism. Such potentiation by IFNs was also observed for PGE2 production, despite the differential regulation of PGD synthase and PGE synthase isoforms mediating PGD2 and PGE2 production under inflammatory conditions. Mechanistic analysis revealed that the generation of intracellular reactive oxygen species (ROS was remarkably potentiated by IFNs and required for PGD2 production, but was nullified by STAT1 deficiency. Conversely, the regulation of STAT1 level and activity by IFNs was largely dependent on ROS levels. Using a model of zymosan-induced peritonitis, the relevance of this finding in vivo was supported by marked inhibition of PGD2 and ROS produced in peritoneal exudate cells by STAT1 deficiency. Collectively, our findings suggest that IFNs, although not activating on their own, are potent amplifiers of TLR-induced PGD2 production via positive-feedback regulation between STAT1 and ROS.

  11. Monocrotophos, an organophosphorus insecticide, disrupts the expression of HpNetrin and its receptor neogenin during early development in the sea urchin (Hemicentrotus pulcherrimus).

    Science.gov (United States)

    Zhang, Xiaona; Xu, Lei; Tian, Hua; Wang, Cuicui; Wang, Wei; Ru, Shaoguo

    2017-09-01

    Netrins, chemotropic guidance cues, can guide the extension of serotonergic axons by binding to netrin receptors during neural development. However, little is known about whether disruption of netrin signaling is involved in the mechanisms by which organophosphorus pesticides affect serotonergic nervous system (SNS) development. In this study, we evaluated the effects of the pesticide monocrotophos (MCP) on the expression patterns of HpNetrin and its receptor neogenin as well as on the intracellular calcium ion (Ca 2+ ) levels in Hemicentrotus pulcherrimus (sea urchin) by exposing fertilized embryos to 0, 0.01, 0.10, and 1.00mg/L MCP. The results showed that MCP disrupted HpNetrin and neogenin expression at different developmental stages in H. pulcherrimus and that Ca 2+ appeared to be involved in the MCP-induced developmental neurotoxicity. Specifically, the lower concentrations of MCP elevated HpNetrin and neogenin transcription, resulting in higher intracellular Ca 2+ levels during the early developmental stages in the sea urchin; this may affect netrin-directed cell migration/axon extension and subsequently disrupt serotonergic axon branching and synapse formation. In contrast, 1.00mg/L MCP exhibited an inhibitory effect on HpNetrin and neogenin transcription. This finding implies that the regulatory roles of these factors may be diminished during early development, thereby causing developmental defects in the sea urchin. Collectively, our results provide a basis for exploring the involvement of netrin and neogenin in the organophosphate-induced disruption of the SNS during development. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Helicobacter-negative gastritis: a distinct entity unrelated to Helicobacter pylori infection.

    Science.gov (United States)

    Genta, R M; Sonnenberg, A

    2015-01-01

    Helicobacter-negative gastritis is diagnosed when no organisms are detected in a gastric mucosa with typical features of Helicobacter gastritis (Hp-gastritis). If Helicobacter-negative gastritis consisted mostly of 'missed' Helicobacter infections, its prevalence should represent a constant percentage of these infections in a population, and their clinico-epidemiological features would overlap. To compare the epidemiologic patterns of Hp-positive and Hp-negative gastritis. From a pathology database, we extracted demographic, clinical and histopathological data from patients with gastric biopsies (1.2008-12.2013). We allocated patients to high (≥12%) and low (≤6%) H. pylori prevalence regions defined by ZIP code-based data. The prevalence of H. pylori-positive and -negative gastritis by sex, age and state were expressed as a per cent of the total study population stratified accordingly. Of 895 323 patients, 10.6% had Hp-gastritis and 1.5% Helicobacter-negative gastritis. Hp-gastritis, but not Helicobacter-negative gastritis, was more common in males than females (OR 1.17, 95% CI: 1.16-1.19). While Hp-gastritis was more prevalent in high than in low-prevalence areas (OR 3.65, 95% CI: 3.57-3.74), Helicobacter-negative gastritis was only minimally affected by the underlying H. pylori prevalence (1.7% vs. 1.5%). The age-specific prevalence of Hp-gastritis peaked in the 4th to 5th decades; Helicobacter-negative gastritis exhibited a low and relatively flat pattern. The geographic distribution of H. pylori-positive and -negative gastritis showed no significant correlation. Intestinal metaplasia was found in 13.0% of patients with Hp-gastritis and in 6.1% of those with Helicobacter-negative gastritis (OR 0.43, 95% CI: 0.40-0.47). These data suggest that Helicobacter-negative gastritis is, in the vast majority of cases, a nosologically and epidemiologically distinct entity that deserves further investigation. © 2014 John Wiley & Sons Ltd.

  13. HP-multigrid as smoother algorithm for higher order discontinuous Galerkin discretizations of advection dominated flows. Part I. Multilevel Analysis

    NARCIS (Netherlands)

    van der Vegt, Jacobus J.W.; Rhebergen, Sander

    2011-01-01

    The hp-Multigrid as Smoother algorithm (hp-MGS) for the solution of higher order accurate space-(time) discontinuous Galerkin discretizations of advection dominated flows is presented. This algorithm combines p-multigrid with h-multigrid at all p-levels, where the h-multigrid acts as smoother in the

  14. 78 FR 61153 - Post-Employment Conflict of Interest Regulations; Exempted Senior Employee Positions

    Science.gov (United States)

    2013-10-03

    ... Regulations; Exempted Senior Employee Positions AGENCY: Office of Government Ethics (OGE). ACTION: Final rule... notice of the revocation of certain regulatory exemptions of senior employee positions at the Securities... employee'' for a period of one year from knowingly making, with the intent to influence, any communication...

  15. Use of a low-background and anti-Compton HpGe gamma-spectrometer in analyses of environmental samples

    Energy Technology Data Exchange (ETDEWEB)

    Qiong, Su; Yamin, Gao [Ministry of Public Health, Beijing, BJ (China). Lab. of Industrial Hygiene

    1989-12-01

    The results of application of a HpGe gamma-spectrometer in the analyses of enviromental samples are reported. The spectrometer has very low background and good property of Compton suppression. By comparison between the gamma-spectra with and without anti-coincidence shield for the same samples, the advantage in analysing environmental samples became apparent. In the analyses of carp samples, the ratio of specific activities of {sup 226}Ra in the flesh and bone of the carp was 1 to 35, which is basically in agreement with the ratio of the accumulation factors 1:37, as reported in the literature. Thus the spectrometer would play an important role in the research of the transfer of radionuclides of low activity in the environment. The method of gamma-ray data processing is also described.

  16. Use of a low-background and anti-Compton HpGe gamma-spectrometer in analyses of environmental samples

    International Nuclear Information System (INIS)

    Su Qiong; Gao Yamin

    1989-01-01

    The results of application of a HpGe gamma-spectrometer in the analyses of enviromental samples are reported. The spectrometer has very low background and good property of Compton suppression. By comparison between the gamma-spectra with and without anti-coincidence shield for the same samples, the advantage in analysing environmental samples became apparent. In the analyses of carp samples, the ratio of specific activities of 226 Ra in the flesh and bone of the carp was 1 to 35, which is basically in agreement with the ratio of the accumulation factors 1:37, as reported in the literature. Thus the spectrometer would play an important role in the research of the transfer of radionuclides of low activity in the environment. The method of gamma-ray data processing is also described

  17. Coupled-Flow Simulation of HP-LP Turbines Has Resulted in Significant Fuel Savings

    Science.gov (United States)

    Veres, Joseph P.

    2001-01-01

    Our objective was to create a high-fidelity Navier-Stokes computer simulation of the flow through the turbines of a modern high-bypass-ratio turbofan engine. The simulation would have to capture the aerodynamic interactions between closely coupled high- and low-pressure turbines. A computer simulation of the flow in the GE90 turbofan engine's high-pressure (HP) and low-pressure (LP) turbines was created at GE Aircraft Engines under contract with the NASA Glenn Research Center. The three-dimensional steady-state computer simulation was performed using Glenn's average-passage approach named APNASA. The areas upstream and downstream of each blade row mutually interact with each other during engine operation. The embedded blade row operating conditions are modeled since the average passage equations in APNASA actively include the effects of the adjacent blade rows. The turbine airfoils, platforms, and casing are actively cooled by compressor bleed air. Hot gas leaks around the tips of rotors through labyrinth seals. The flow exiting the high work HP turbines is partially transonic and, therefore, has a strong shock system in the transition region. The simulation was done using 121 processors of a Silicon Graphics Origin 2000 (NAS 02K) cluster at the NASA Ames Research Center, with a parallel efficiency of 87 percent in 15 hr. The typical average-passage analysis mesh size per blade row was 280 by 45 by 55, or approx.700,000 grid points. The total number of blade rows was 18 for a combined HP and LP turbine system including the struts in the transition duct and exit guide vane, which contain 12.6 million grid points. Design cycle turnaround time requirements ran typically from 24 to 48 hr of wall clock time. The number of iterations for convergence was 10,000 at 8.03x10(exp -5) sec/iteration/grid point (NAS O2K). Parallel processing by up to 40 processors is required to meet the design cycle time constraints. This is the first-ever flow simulation of an HP and LP

  18. [Pr2(pdc3(Hpdc(H2O4]n·n(H3hp·8n(H2O, a One-Dimensional Coordination Polymer Containing PrO6N3 Tri-Capped Trigonal Prisms and PrO8N Mono-Capped Square Anti-Prisms (H2pdc = Pyridine 2,6-Dicarboxylic Acid, C7H5NO4; 3hp = 3-Hydroxy Pyridine, C5H5NO

    Directory of Open Access Journals (Sweden)

    Shahzad Sharif

    2012-08-01

    Full Text Available The synthesis, structure and some properties of the one-dimensional coordination polymer, [Pr2(pdc3(Hpdc]n·n(H3hp·8n(H2O, (H2pdc = pyridine 2,6-dicarboxylic acid, C7H5NO4; 3hp = 3-hydroxypyridine, C5H5NO are described. One of the Pr3+ ions is coordinated by two O,N,O-tridentate pdc2− ligands and one tridentate Hpdc− anion to generate a fairly regular PrO6N3 tri-capped trigonal prism, with the N atoms acting as the caps. The second Pr3+ ion is coordinated by one tridentate pdc2− dianion, four water molecules and two monodentate bridging pdc2− ligands to result in a PrO8N coordination polyhedron that approximates to a mono-capped square-anti-prism. The ligands bridge the metal-atom nodes into a chain, which extends in the [100] direction. The H3hp+ cation and uncoordinated water molecules occupy the inter-chain regions and an N–HLO and numerous O–HLO hydrogen bonds consolidate the structure. The H3hp+ species appears to intercalate between pendant pdc rings to consolidate the polymeric structure. Crystal data: 1 (C33H43N5O29Pr2, Mr = 1255.54, triclinic,  (No. 2, Z = 2, a = 13.2567(1 Å, b = 13.6304(2 Å, c = 13.6409(2 Å, α = 89.695(1°, β = 63.049(1°, γ = 86.105(1°, V = 2191.16(5 Å3, R(F = 0.033, wR(F2 = 0.084.

  19. Targeted deficiency of the transcriptional activator Hnf1alpha alters subnuclear positioning of its genomic targets.

    Directory of Open Access Journals (Sweden)

    Reini F Luco

    2008-05-01

    Full Text Available DNA binding transcriptional activators play a central role in gene-selective regulation. In part, this is mediated by targeting local covalent modifications of histone tails. Transcriptional regulation has also been associated with the positioning of genes within the nucleus. We have now examined the role of a transcriptional activator in regulating the positioning of target genes. This was carried out with primary beta-cells and hepatocytes freshly isolated from mice lacking Hnf1alpha, an activator encoded by the most frequently mutated gene in human monogenic diabetes (MODY3. We show that in Hnf1a-/- cells inactive endogenous Hnf1alpha-target genes exhibit increased trimethylated histone H3-Lys27 and reduced methylated H3-Lys4. Inactive Hnf1alpha-targets in Hnf1a-/- cells are also preferentially located in peripheral subnuclear domains enriched in trimethylated H3-Lys27, whereas active targets in wild-type cells are positioned in more central domains enriched in methylated H3-Lys4 and RNA polymerase II. We demonstrate that this differential positioning involves the decondensation of target chromatin, and show that it is spatially restricted rather than a reflection of non-specific changes in the nuclear organization of Hnf1a-deficient cells. This study, therefore, provides genetic evidence that a single transcriptional activator can influence the subnuclear location of its endogenous genomic targets in primary cells, and links activator-dependent changes in local chromatin structure to the spatial organization of the genome. We have also revealed a defect in subnuclear gene positioning in a model of a human transcription factor disease.

  20. Investigation of HP Turbine Blade Failure in a Military Turbofan Engine

    Science.gov (United States)

    Mishra, R. K.; Thomas, Johny; Srinivasan, K.; Nandi, Vaishakhi; Bhatt, R. Raghavendra

    2017-04-01

    Failure of a high pressure (HP) turbine blade in a military turbofan engine is investigated to determine the root cause of failure. Forensic and metallurgical investigations are carried out on the affected blades. The loss of coating and the presence of heavily oxidized intergranular fracture features including substrate material aging and airfoil curling in the trailing edge of a representative blade indicate that the coating is not providing adequate oxidation protection and the blade material substrate is not suitable for the application at hand. Coating spallation followed by substrate oxidation and aging leading to intergranular cracking and localized trailing edge curling is the root cause of the blade failure. The remaining portion of the blade fracture surface showed ductile overload features in the final failure. The damage observed in downstream components is due to secondary effects.

  1. Strategies to regulate transcription factor-mediated gene positioning and interchromosomal clustering at the nuclear periphery.

    Science.gov (United States)

    Randise-Hinchliff, Carlo; Coukos, Robert; Sood, Varun; Sumner, Michael Chas; Zdraljevic, Stefan; Meldi Sholl, Lauren; Garvey Brickner, Donna; Ahmed, Sara; Watchmaker, Lauren; Brickner, Jason H

    2016-03-14

    In budding yeast, targeting of active genes to the nuclear pore complex (NPC) and interchromosomal clustering is mediated by transcription factor (TF) binding sites in the gene promoters. For example, the binding sites for the TFs Put3, Ste12, and Gcn4 are necessary and sufficient to promote positioning at the nuclear periphery and interchromosomal clustering. However, in all three cases, gene positioning and interchromosomal clustering are regulated. Under uninducing conditions, local recruitment of the Rpd3(L) histone deacetylase by transcriptional repressors blocks Put3 DNA binding. This is a general function of yeast repressors: 16 of 21 repressors blocked Put3-mediated subnuclear positioning; 11 of these required Rpd3. In contrast, Ste12-mediated gene positioning is regulated independently of DNA binding by mitogen-activated protein kinase phosphorylation of the Dig2 inhibitor, and Gcn4-dependent targeting is up-regulated by increasing Gcn4 protein levels. These different regulatory strategies provide either qualitative switch-like control or quantitative control of gene positioning over different time scales. © 2016 Randise-Hinchliff et al.

  2. Position Control of Pneumatic Actuator Using Self-Regulation Nonlinear PID

    Directory of Open Access Journals (Sweden)

    Syed Najib Syed Salim

    2014-01-01

    Full Text Available The enhancement of nonlinear PID (N-PID controller for a pneumatic positioning system is proposed to improve the performance of this controller. This is executed by utilizing the characteristic of rate variation of the nonlinear gain that is readily available in N-PID controller. The proposed equation, namely, self-regulation nonlinear function (SNF, is used to reprocess the error signal with the purpose of generating the value of the rate variation, continuously. With the addition of this function, a new self-regulation nonlinear PID (SN-PID controller is proposed. The proposed controller is then implemented to a variably loaded pneumatic actuator. Simulation and experimental tests are conducted with different inputs, namely, step, multistep, and random waveforms, to evaluate the performance of the proposed technique. The results obtained have been proven as a novel initiative at examining and identifying the characteristic based on a new proposal controller resulting from N-PID controller. The transient response is improved by a factor of 2.2 times greater than previous N-PID technique. Moreover, the performance of pneumatic positioning system is remarkably good under various loads.

  3. Perfectionism and negative/positive affect associations: the role of cognitive emotion regulation and perceived distress/coping.

    Science.gov (United States)

    Castro, Juliana; Soares, Maria João; Pereira, Ana T; Macedo, António

    2017-01-01

    To explore 1) if perfectionism, perceived distress/coping, and cognitive emotion regulation (CER) are associated with and predictive of negative/positive affect (NA/PA); and 2) if CER and perceived distress/coping are associated with perfectionism and if they mediate the perfectionism-NA/PA associations. There is a distinction between maladaptive and adaptive perfectionism in its association with NA/PA. CER and perceived distress/coping may mediate the maladaptive/adaptive perfectionism and NA/PA associations. 344 students (68.4% girls) completed the Hewitt & Flett and the Frost Multidimensional Perfectionism Scales, the Composite Multidimensional Perfectionism Scale, the Profile of Mood States, the Perceived Stress Scale, and the Cognitive Emotion Regulation Questionnaire. NA predictors were maladaptive/adaptive perfectionism, maladaptive CER and perceived distress (positively), positive reappraisal and planning, and perceived coping (negatively). PA predictors were maladaptive/adaptive perfectionism and perceived distress (negatively), positive reappraisal and planning, positive refocusing and perceived coping (positively). The association between maladaptive perfectionism and NA was mediated by maladaptive CER/low adaptive CER, perceived distress/low coping. Maladaptive perfectionism and low PA association was mediated by perceived distress. High PA was determined by low maladaptive perfectionism and this association was mediated by adaptive REC and coping. Adaptive perfectionism and NA association was mediated by maladaptive CER and perceived distress. CER and perceived distress/coping are associated and mediate the perfectionism-NA/PA associations.

  4. The Protein Kinase SmSnRK2.6 Positively Regulates Phenolic Acid Biosynthesis in Salvia miltiorrhiza by Interacting with SmAREB1.

    Science.gov (United States)

    Jia, Yanyan; Bai, Zhenqing; Pei, Tianlin; Ding, Kai; Liang, Zongsuo; Gong, Yuehua

    2017-01-01

    Subclass III members of the sucrose non-fermenting-1-related protein kinase 2 (SnRK2) play essential roles in both the abscisic acid signaling and abiotic stress responses of plants by phosphorylating the downstream ABA-responsive element (ABRE)-binding proteins (AREB/ABFs). This comprehensive study investigated the function of new candidate genes, namely SmSnRK2.3 , SmSnRK2.6 , and SmAREB1 , with a view to breeding novel varieties of Salvia miltiorrhiza with improved stress tolerance stresses and more content of bioactive ingredients. Exogenous ABA strongly induced the expression of these genes. PlantCARE predicted several hormones and stress response cis -elements in their promoters. SmSnRK2.6 and SmAREB1 showed the highest expression levels in the leaves of S. miltiorrhiza seedlings, while SmSnRK2.3 exhibited a steady expression in their roots, stems, and leaves. A subcellular localization assay revealed that both SmSnRK2.3 and SmSnRK2.6 were located in the cell membrane, cytoplasm, and nucleus, whereas SmAREB1 was exclusive to the nucleus. Overexpressing SmSnRK2.3 did not significantly promote the accumulation of rosmarinic acid (RA) and salvianolic acid B (Sal B) in the transgenic S. miltiorrhiza hairy roots. However, overexpressing SmSnRK2.6 and SmAREB1 increased the contents of RA and Sal B, and regulated the expression levels of structural genes participating in the phenolic acid-branched and side-branched pathways, including SmPAL1 , SmC4H , Sm4CL1 , SmTAT , SmHPPR , SmRAS , SmCHS , SmCCR , SmCOMT , and SmHPPD . Furthermore, SmSnRK2.3 and SmSnRK2.6 interacted physically with SmAREB1. In summary, our results indicate that SmSnRK2.6 is involved in stress responses and can regulate structural gene transcripts to promote greater metabolic flux to the phenolic acid-branched pathway, via its interaction with SmAREB1 , a transcription factor. In this way, SmSnRK2.6 contributes to the positive regulation of phenolic acids in S. miltiorrhiza hairy roots.

  5. The Protein Kinase SmSnRK2.6 Positively Regulates Phenolic Acid Biosynthesis in Salvia miltiorrhiza by Interacting with SmAREB1

    Directory of Open Access Journals (Sweden)

    Yanyan Jia

    2017-08-01

    Full Text Available Subclass III members of the sucrose non-fermenting-1-related protein kinase 2 (SnRK2 play essential roles in both the abscisic acid signaling and abiotic stress responses of plants by phosphorylating the downstream ABA-responsive element (ABRE-binding proteins (AREB/ABFs. This comprehensive study investigated the function of new candidate genes, namely SmSnRK2.3, SmSnRK2.6, and SmAREB1, with a view to breeding novel varieties of Salvia miltiorrhiza with improved stress tolerance stresses and more content of bioactive ingredients. Exogenous ABA strongly induced the expression of these genes. PlantCARE predicted several hormones and stress response cis-elements in their promoters. SmSnRK2.6 and SmAREB1 showed the highest expression levels in the leaves of S. miltiorrhiza seedlings, while SmSnRK2.3 exhibited a steady expression in their roots, stems, and leaves. A subcellular localization assay revealed that both SmSnRK2.3 and SmSnRK2.6 were located in the cell membrane, cytoplasm, and nucleus, whereas SmAREB1 was exclusive to the nucleus. Overexpressing SmSnRK2.3 did not significantly promote the accumulation of rosmarinic acid (RA and salvianolic acid B (Sal B in the transgenic S. miltiorrhiza hairy roots. However, overexpressing SmSnRK2.6 and SmAREB1 increased the contents of RA and Sal B, and regulated the expression levels of structural genes participating in the phenolic acid-branched and side-branched pathways, including SmPAL1, SmC4H, Sm4CL1, SmTAT, SmHPPR, SmRAS, SmCHS, SmCCR, SmCOMT, and SmHPPD. Furthermore, SmSnRK2.3 and SmSnRK2.6 interacted physically with SmAREB1. In summary, our results indicate that SmSnRK2.6 is involved in stress responses and can regulate structural gene transcripts to promote greater metabolic flux to the phenolic acid-branched pathway, via its interaction with SmAREB1, a transcription factor. In this way, SmSnRK2.6 contributes to the positive regulation of phenolic acids in S. miltiorrhiza hairy roots.

  6. Mit1 Transcription Factor Mediates Methanol Signaling and Regulates the Alcohol Oxidase 1 (AOX1) Promoter in Pichia pastoris.

    Science.gov (United States)

    Wang, Xiaolong; Wang, Qi; Wang, Jinjia; Bai, Peng; Shi, Lei; Shen, Wei; Zhou, Mian; Zhou, Xiangshan; Zhang, Yuanxing; Cai, Menghao

    2016-03-18

    The alcohol oxidase 1 (AOX1) promoter (P AOX1) of Pichia pastoris is the most powerful and commonly used promoter for driving protein expression. However, mechanisms regulating its transcriptional activity are unclear. Here, we identified a Zn(II)2Cys6-type methanol-induced transcription factor 1 (Mit1) and elucidated its roles in regulating PAOX1 activity in response to glycerol and methanol. Mit1 regulated the expression of many genes involved in methanol utilization pathway, including AOX1, but did not participate in peroxisome proliferation and transportation of peroxisomal proteins during methanol metabolism. Structural analysis of Mit1 by performing domain deletions confirmed its specific and critical role in the strict repression of P AOX1 in glycerol medium. Importantly, Mit1, Mxr1, and Prm1, which positively regulated P AOX1 in response to methanol, were bound to P AOX1 at different sites and did not interact with each other. However, these factors cooperatively activated P AOX1 through a cascade. Mxr1 mainly functioned during carbon derepression, whereas Mit1 and Prm1 functioned during methanol induction, with Prm1 transmitting methanol signal to Mit1 by binding to the MIT1 promoter (P MIT1), thus increasingly expressing Mit1 and subsequently activating P AOX1. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Safety regulation KTA 3901: Communication systems for nuclear power plants

    International Nuclear Information System (INIS)

    1981-01-01

    The regulation applies to communication systems in stationary nuclear power plants with at least one power plant unit, i.e. alarm systems, staff locator systems, communicators, and systems for external communication. The regulation determines the type and extent of staff communication systems as well as the demands to be made on layout, installation, operating systems, and testing of communication systems for nuclear power plants. (orig./HP) [de

  8. Test of ring, eye lens and whole body dosemeters for the dose quantity Hp(3) to be used in interventional radiology

    Science.gov (United States)

    Szumska, A.; Budzanowski, M.; Kopeć, R.

    2017-11-01

    In its statement on tissue reactions approved on 21st April 2011, the International Commission on Radiological Protection (ICRP, 2012) reviewed its recommendation concerning the equivalent dose limit for the eye lens and reduced the dose limits for occupationally exposed persons to 20 mSv in a year, averaged over defined periods of 5 years, with no single year exceeding 50 mSv. This limit was approved and written down in the new EURATOM (European Atomic Energy Community) directive 2013/59 and in the IAEA (International Atomic Energy Agency) BSS (Basic Safety Standard) of July 2014. For that reason, the necessity to monitor the eye lens may become more important than it was before. However, specially dedicated dosemeters for the dose quantity Hp(3) are using very rarely. Commonly use are only whole body personal dosemeters for the personal dose equivalent quantities Hp(10) worn on the trunk and ring dosemeters worn on finger to measure the quantity Hp(0.07). Therefore, in this work it was investigated whether dosemeters from routine use calibrated in terms of Hp(10) and Hp(0.07) and worn on thyroid collar and protective apron could deliver similar results like dedicated eye lens dosemeter worn close to the eyes. The results show that the best method if dedicated eye lens dosimeters is not used is to measure doses in terms of Hp(0.07) on the thyroid collar (Pearson product, r=0.85). Obtained results shows also importance of proper localization of eye lens dosimeter (close to the eye, from side of the X-ray source).

  9. Mcm1p binding sites in ARG1 positively regulate Gcn4p binding and SWI/SNF recruitment

    OpenAIRE

    Yoon, Sungpil; Hinnebusch, Alan G.

    2009-01-01

    Transcription of the arginine biosynthetic gene ARG1 is activated by Gcn4p, a transcription factor induced by starvation for any amino acid. Previously we showed that Gcn4p binding stimulates the recruitment of Mcm1p and co-activator SWI/SNF to ARG1 in cells via Gcn4p induction through amino acid starvation. Here we report that Gcn4p binding is reduced by point mutations of the Mcm1p binding site and increased by overexpression of Mcm1p. This result suggests that Mcm1p plays a positive role i...

  10. Salt Stress Represses Soybean Seed Germination by Negatively Regulating GA Biosynthesis While Positively Mediating ABA Biosynthesis.

    Science.gov (United States)

    Shu, Kai; Qi, Ying; Chen, Feng; Meng, Yongjie; Luo, Xiaofeng; Shuai, Haiwei; Zhou, Wenguan; Ding, Jun; Du, Junbo; Liu, Jiang; Yang, Feng; Wang, Qiang; Liu, Weiguo; Yong, Taiwen; Wang, Xiaochun; Feng, Yuqi; Yang, Wenyu

    2017-01-01

    Soybean is an important and staple oilseed crop worldwide. Salinity stress has adverse effects on soybean development periods, especially on seed germination and post-germinative growth. Improving seed germination and emergence will have positive effects under salt stress conditions on agricultural production. Here we report that NaCl delays soybean seed germination by negatively regulating gibberellin (GA) while positively mediating abscisic acid (ABA) biogenesis, which leads to a decrease in the GA/ABA ratio. This study suggests that fluridone (FLUN), an ABA biogenesis inhibitor, might be a potential plant growth regulator that can promote soybean seed germination under saline stress. Different soybean cultivars, which possessed distinct genetic backgrounds, showed a similar repressed phenotype during seed germination under exogenous NaCl application. Biochemical analysis revealed that NaCl treatment led to high MDA (malondialdehyde) level during germination and the post-germinative growth stages. Furthermore, catalase, superoxide dismutase, and peroxidase activities also changed after NaCl treatment. Subsequent quantitative Real-Time Polymerase Chain Reaction analysis showed that the transcription levels of ABA and GA biogenesis and signaling genes were altered after NaCl treatment. In line with this, phytohormone measurement also revealed that NaCl considerably down-regulated active GA 1 , GA 3 , and GA 4 levels, whereas the ABA content was up-regulated; and therefore ratios, such as GA 1 /ABA, GA 3 /ABA, and GA 4 /ABA, are decreased. Consistent with the hormonal quantification, FLUN partially rescued the delayed-germination phenotype caused by NaCl-treatment. Altogether, these results demonstrate that NaCl stress inhibits soybean seed germination by decreasing the GA/ABA ratio, and that FLUN might be a potential plant growth regulator that could promote soybean seed germination under salinity stress.

  11. Salt Stress Represses Soybean Seed Germination by Negatively Regulating GA Biosynthesis While Positively Mediating ABA Biosynthesis

    Directory of Open Access Journals (Sweden)

    Kai Shu

    2017-08-01

    Full Text Available Soybean is an important and staple oilseed crop worldwide. Salinity stress has adverse effects on soybean development periods, especially on seed germination and post-germinative growth. Improving seed germination and emergence will have positive effects under salt stress conditions on agricultural production. Here we report that NaCl delays soybean seed germination by negatively regulating gibberellin (GA while positively mediating abscisic acid (ABA biogenesis, which leads to a decrease in the GA/ABA ratio. This study suggests that fluridone (FLUN, an ABA biogenesis inhibitor, might be a potential plant growth regulator that can promote soybean seed germination under saline stress. Different soybean cultivars, which possessed distinct genetic backgrounds, showed a similar repressed phenotype during seed germination under exogenous NaCl application. Biochemical analysis revealed that NaCl treatment led to high MDA (malondialdehyde level during germination and the post-germinative growth stages. Furthermore, catalase, superoxide dismutase, and peroxidase activities also changed after NaCl treatment. Subsequent quantitative Real-Time Polymerase Chain Reaction analysis showed that the transcription levels of ABA and GA biogenesis and signaling genes were altered after NaCl treatment. In line with this, phytohormone measurement also revealed that NaCl considerably down-regulated active GA1, GA3, and GA4 levels, whereas the ABA content was up-regulated; and therefore ratios, such as GA1/ABA, GA3/ABA, and GA4/ABA, are decreased. Consistent with the hormonal quantification, FLUN partially rescued the delayed-germination phenotype caused by NaCl-treatment. Altogether, these results demonstrate that NaCl stress inhibits soybean seed germination by decreasing the GA/ABA ratio, and that FLUN might be a potential plant growth regulator that could promote soybean seed germination under salinity stress.

  12. Cytoprotective effect exerted by geraniin in HepG2 cells is through microRNA mediated regulation of BACH-1 and HO-1.

    Science.gov (United States)

    Aayadi, Hoda; Mittal, Smriti P K; Deshpande, Anjali; Gore, Makarand; Ghaskadbi, Saroj S

    2017-11-01

    Geraniin, a hydrolysable tannin, used in traditional medicine in Southeast Asia, is known to exhibit various biological activities. As an antioxidant it is known to up-regulate phase II enzyme Heme oxygenase-1 (HO-1). However its mechanism is not clearly understood. Nuclear factor erythroid-derived 2 related factor 2 (Nrf-2) is transcriptionally up-regulated by Extracellular signal-regulated kinase (ERK) 1/2 and retained in nucleus due to inactivated Glycogen synthase kinase 3 beta (GSK-3β). Geraniin additionally down-regulates expression of microRNA 217 and 377 (miR-217 and miR-377) which target HO-1 mRNA. Expression of BTB and CNC homolog 1 (BACH-1), another regulator of HO-1, is also down-regulated by up-regulating microRNA 98 (miR-98), a negative regulator of BACH-1. Thus, geraniin up-regulates HO-1 expression both through activating its positive regulator Nrf-2 and by down-regulating its negative regulator BACH-1. Up-regulation of HO-1 also confers protection to HepG2 cells from tertiary butyl hydroperoxide (TBH) induced cytotoxicity. [BMB Reports 2017; 50(11): 560-565].

  13. Regulation of the Hippocampal Network by VGLUT3-Positive CCK- GABAergic Basket Cells

    Directory of Open Access Journals (Sweden)

    Caroline Fasano

    2017-05-01

    Full Text Available Hippocampal interneurons release the inhibitory transmitter GABA to regulate excitation, rhythm generation and synaptic plasticity. A subpopulation of GABAergic basket cells co-expresses the GABA/glycine vesicular transporters (VIAAT and the atypical type III vesicular glutamate transporter (VGLUT3; therefore, these cells have the ability to signal with both GABA and glutamate. GABAergic transmission by basket cells has been extensively characterized but nothing is known about the functional implications of VGLUT3-dependent glutamate released by these cells. Here, using VGLUT3-null mice we observed that the loss of VGLUT3 results in a metaplastic shift in synaptic plasticity at Shaeffer’s collaterals – CA1 synapses and an altered theta oscillation. These changes were paralleled by the loss of a VGLUT3-dependent inhibition of GABAergic current in CA1 pyramidal layer. Therefore presynaptic type III metabotropic could be activated by glutamate released from VGLUT3-positive interneurons. This putative presynaptic heterologous feedback mechanism inhibits local GABAergic tone and regulates the hippocampal neuronal network.

  14. Vibration and Stability of 3000-hp, Titanium Chemical Process Blower

    Directory of Open Access Journals (Sweden)

    Les Gutzwiller

    2003-01-01

    Full Text Available This 74-in-diameter blower had an overhung rotor design of titanium construction, operating at 50 pounds per square inch gauge in a critical chemical plant process. The shaft was supported by oil-film bearings and was directdriven by a 3000-hp electric motor through a metal disk type of coupling. The operating speed was 1780 rpm. The blower shaft and motor shaft motion was monitored by Bently Nevada proximity probes and a Model 3100 monitoring system.

  15. Multilayered Regulation of Ethylene Induction Plays a Positive Role in Arabidopsis Resistance against Pseudomonas syringae1[OPEN

    Science.gov (United States)

    Guan, Rongxia; Su, Jianbin; Meng, Xiangzong; Li, Sen; Liu, Yidong; Xu, Juan; Zhang, Shuqun

    2015-01-01

    Ethylene, a key phytohormone involved in plant-pathogen interaction, plays a positive role in plant resistance against fungal pathogens. However, its function in plant bacterial resistance remains unclear. Here, we report a detailed analysis of ethylene induction in Arabidopsis (Arabidopsis thaliana) in response to Pseudomonas syringae pv tomato DC3000 (Pst). Ethylene biosynthesis is highly induced in both pathogen/microbe-associated molecular pattern (PAMP)-triggered immunity and effector-triggered immunity (ETI), and the induction is potentiated by salicylic acid (SA) pretreatment. In addition, Pst actively suppresses PAMP-triggered ethylene induction in a type III secretion system-dependent manner. SA potentiation of ethylene induction is dependent mostly on MITOGEN-ACTIVATED PROTEIN KINASE6 (MPK6) and MPK3 and their downstream ACS2 and ACS6, two type I isoforms of 1-aminocyclopropane-1-carboxylic acid synthases (ACSs). ACS7, a type III ACS whose expression is enhanced by SA pretreatment, is also involved. Pst expressing the avrRpt2 effector gene (Pst-avrRpt2), which is capable of triggering ETI, induces a higher level of ethylene production, and the elevated portion is dependent on SALICYLIC ACID INDUCTION DEFICIENT2 and NONEXPRESSER OF PATHOGENESIS-RELATED GENE1, two key players in SA biosynthesis and signaling. High-order ACS mutants with reduced ethylene induction are more susceptible to both Pst and Pst-avrRpt2, demonstrating a positive role of ethylene in plant bacterial resistance mediated by both PAMP-triggered immunity and ETI. PMID:26265775

  16. Both sides of the same coin: Rac1 splicing regulating by EGF signaling.

    Science.gov (United States)

    Fu, Xiang-Dong

    2017-04-01

    EGF, a well-studied mitogen for cancer cells, is revealed to induce an E3 ubiquitin ligase adaptor SPSB1, which recruits the Elongin B/C-Collin complex to trigger ubiquitylation of the negative splicing regulator hnRNP A1. This event is synergized with EGF-activated SR proteins to alter alternative splicing of a key small GTPase Rac1 to enhance cell migration, highlighting converging EGF signals on both negative and positive splicing regulators to jointly promote a key cancer pathway.

  17. Spo0A positively regulates epr expression by negating the ...

    Indian Academy of Sciences (India)

    2013-03-07

    Mar 7, 2013 ... ly regulate the epr expression by the process of co-repression. (Kodgire et al. 2006). ... Bacterial strains and plasmids used in this study are listed in table 1. E. coli DH5α ... Wherever necessary, antibiotics were added to the ...

  18. Wingless is a positive regulator of eyespot color patterns in Bicyclus anynana butterflies.

    Science.gov (United States)

    Özsu, Nesibe; Chan, Qian Yi; Chen, Bin; Gupta, Mainak Das; Monteiro, Antónia

    2017-09-01

    Eyespot patterns of nymphalid butterflies are an example of a novel trait yet, the developmental origin of eyespots is still not well understood. Several genes have been associated with eyespot development but few have been tested for function. One of these genes is the signaling ligand, wingless, which is expressed in the eyespot centers during early pupation and may function in eyespot signaling and color ring differentiation. Here we tested the function of wingless in wing and eyespot development by down-regulating it in transgenic Bicyclus anynana butterflies via RNAi driven by an inducible heat-shock promoter. Heat-shocks applied during larval and early pupal development led to significant decreases in wingless mRNA levels and to decreases in eyespot size and wing size in adult butterflies. We conclude that wingless is a positive regulator of eyespot and wing development in B. anynana butterflies. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Passion for a Cause: How It Affects Health and Subjective Well-Being.

    Science.gov (United States)

    St-Louis, Ariane C; Carbonneau, Noémie; Vallerand, Robert J

    2016-06-01

    Using the dualistic model of passion (Vallerand et al., 2003), this research investigated how harmonious passion (HP) or obsessive passion (OP) for a cause can affect volunteers' health and subjective well-being. Three studies with volunteers for local (local emergency crises and community help) and international (humanitarian missions) causes assessed physical and psychological health using cross-sectional and longitudinal designs. Study 1 (N = 108) showed that HP was positively related to satisfaction with one's involvement in the cause and unrelated to physical injuries due to cause involvement. OP was unrelated to satisfaction but positively associated with injuries. Findings were replicated in Study 2 (N = 83). Moreover, self-neglect mediated the positive and negative effects of HP and OP, respectively, on injuries. Study 3 (N = 77) revealed that HP predicted an increase in satisfaction and health over a 3-month mission. OP predicted an increase in physical symptoms and a decrease in health. Furthermore, OP before a mission was positively related to self-neglect that was positively associated with physical symptoms after a mission. OP also positively predicted rumination that was conducive to posttraumatic stress disorder. HP was unrelated to these variables. Findings underscore the role of passion for a cause in predicting intrapersonal outcomes of volunteers. © 2014 Wiley Periodicals, Inc.

  20. The SUD1 gene encodes a putative E3 ubiquitin ligase and is a positive regulator of 3-hydroxy-3-methylglutaryl coenzyme a reductase activity in Arabidopsis.

    Science.gov (United States)

    Doblas, Verónica G; Amorim-Silva, Vítor; Posé, David; Rosado, Abel; Esteban, Alicia; Arró, Montserrat; Azevedo, Herlander; Bombarely, Aureliano; Borsani, Omar; Valpuesta, Victoriano; Ferrer, Albert; Tavares, Rui M; Botella, Miguel A

    2013-02-01

    The 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) enzyme catalyzes the major rate-limiting step of the mevalonic acid (MVA) pathway from which sterols and other isoprenoids are synthesized. In contrast with our extensive knowledge of the regulation of HMGR in yeast and animals, little is known about this process in plants. To identify regulatory components of the MVA pathway in plants, we performed a genetic screen for second-site suppressor mutations of the Arabidopsis thaliana highly drought-sensitive drought hypersensitive2 (dry2) mutant that shows decreased squalene epoxidase activity. We show that mutations in SUPPRESSOR OF DRY2 DEFECTS1 (SUD1) gene recover most developmental defects in dry2 through changes in HMGR activity. SUD1 encodes a putative E3 ubiquitin ligase that shows sequence and structural similarity to yeast Degradation of α factor (Doα10) and human TEB4, components of the endoplasmic reticulum-associated degradation C (ERAD-C) pathway. While in yeast and animals, the alternative ERAD-L/ERAD-M pathway regulates HMGR activity by controlling protein stability, SUD1 regulates HMGR activity without apparent changes in protein content. These results highlight similarities, as well as important mechanistic differences, among the components involved in HMGR regulation in plants, yeast, and animals.

  1. Arabidopsis YAK1 regulates abscisic acid response and drought resistance.

    Science.gov (United States)

    Kim, Dongjin; Ntui, Valentine Otang; Xiong, Liming

    2016-07-01

    Abscisic acid (ABA) is an important phytohormone that controls several plant processes such as seed germination, seedling growth, and abiotic stress response. Here, we report that AtYak1 plays an important role in ABA signaling and postgermination growth in Arabidopsis. AtYak1 knockout mutant plants were hyposensitive to ABA inhibition of seed germination, cotyledon greening, seedling growth, and stomatal movement. atyak1-1 mutant plants display reduced drought stress resistance, as evidenced by water loss rate and survival rate. Molecular genetic analysis revealed that AtYak1 deficiency led to elevated expression of stomatal-related gene, MYB60, and down-regulation of several stress-responsive genes. Altogether, these results indicate that AtYak1 plays a role as a positive regulator in ABA-mediated drought response in Arabidopsis. © 2016 Federation of European Biochemical Societies.

  2. Arabidopsis YAK1 regulates abscisic acid response and drought resistance

    KAUST Repository

    Kim, Dongjin

    2016-06-06

    Abscisic acid (ABA) is an important phytohormone that controls several plant processes such as seed germination, seedling growth, and abiotic stress response. Here, we report that AtYak1 plays an important role in ABA signaling and postgermination growth in Arabidopsis. AtYak1 knockout mutant plants were hyposensitive to ABA inhibition of seed germination, cotyledon greening, seedling growth, and stomatal movement. atyak1-1 mutant plants display reduced drought stress resistance, as evidenced by water loss rate and survival rate. Molecular genetic analysis revealed that AtYak1 deficiency led to elevated expression of stomatal-related gene, MYB60, and down-regulation of several stress-responsive genes. Altogether, these results indicate that AtYak1 plays a role as a positive regulator in ABA-mediated drought response in Arabidopsis. © 2016 Federation of European Biochemical Societies.

  3. Mechanical behaviour of Astm A 297 grade Hp joints welded using different processes

    International Nuclear Information System (INIS)

    Emygdio, Paulo Roberto Oliveira; Zeemann, Annelise; Almeida, Luiz Henrique de

    1996-01-01

    The influence of different arc welding processes on mechanical behaviour was studied for cast heat resistant stainless steel welded joints, in the as welded conditions. ASTM A 297 grade HP with niobium and niobium/titanium additions were welded following three different welding procedures, using shielded metal arc welding gas tungsten arc welding and plasma arc welding, in six welded joints. The welded joint mechanical behaviour was evaluated by ambient temperature and 870 deg C tensile tests; and creep tests at 900 deg C and 50 MPa. Mechanical test results showed that the welding procedure qualification following welding codes is not suitable for high temperature service applications. (author)

  4. Quantitative kinetics of In-111 autologous (In-AP) and homologous (Cr-HP) platelets in immune thrombocytopenic purpura (ITP)

    International Nuclear Information System (INIS)

    Lotter, M.G.; Heyns, A.D.P.; Badenhorst, P.N.; Minnaar, P.C.

    1984-01-01

    Contrary to the accepted view, the authors have found that platelet turnover is not always increased in ITP if the mean platelet survival time (PS) is measured with In-AP. The authors investigated the possible cause of the discrepancy by comparing kinetics of In-AP with those of Cr-HP in 10 patients with ITP. PS was estimated with the multiple hit model. The equilibrium and final in vivo distribution of In-AP was quantitated with the geometrical mean method. The patients could be divided into either those with splenic or diffuse RES platelet destruction. The authors conclude that in ITP platelet survival of In-AP is significantly (P < .05) longer than that of Cr-HP. Platelet turnover measured with In-AP is only normal in patients with mainly splenic platelet sequestration. Results with Cr-HP give a false impression of PS. It seems that in ITP those patients with severe disease also have a platelet production defect

  5. The histone demethylase Jhdm1a regulates hepatic gluconeogenesis.

    Directory of Open Access Journals (Sweden)

    Dongning Pan

    Full Text Available Hepatic gluconeogenesis is required for maintaining blood glucose homeostasis; yet, in diabetes mellitus, this process is unrestrained and is a major contributor to fasting hyperglycemia. To date, the impacts of chromatin modifying enzymes and chromatin landscape on gluconeogenesis are poorly understood. Through catalyzing the removal of methyl groups from specific lysine residues in the histone tail, histone demethylases modulate chromatin structure and, hence, gene expression. Here we perform an RNA interference screen against the known histone demethylases and identify a histone H3 lysine 36 (H3K36 demethylase, Jhdm1a, as a key negative regulator of gluconeogenic gene expression. In vivo, silencing of Jhdm1a promotes liver glucose synthesis, while its exogenous expression reduces blood glucose level. Importantly, the regulation of gluconeogenesis by Jhdm1a requires its demethylation activity. Mechanistically, we find that Jhdm1a regulates the expression of a major gluconeogenic regulator, C/EBPα. This is achieved, at least in part, by its USF1-dependent association with the C/EBPα promoter and its subsequent demethylation of dimethylated H3K36 on the C/EBPα locus. Our work provides compelling evidence that links histone demethylation to transcriptional regulation of gluconeogenesis and has important implications for the treatment of diabetes.

  6. The Histone Demethylase Jhdm1a Regulates Hepatic Gluconeogenesis

    Science.gov (United States)

    Zou, Tie; Yao, Annie Y.; Cooper, Marcus P.; Boyartchuk, Victor; Wang, Yong-Xu

    2012-01-01

    Hepatic gluconeogenesis is required for maintaining blood glucose homeostasis; yet, in diabetes mellitus, this process is unrestrained and is a major contributor to fasting hyperglycemia. To date, the impacts of chromatin modifying enzymes and chromatin landscape on gluconeogenesis are poorly understood. Through catalyzing the removal of methyl groups from specific lysine residues in the histone tail, histone demethylases modulate chromatin structure and, hence, gene expression. Here we perform an RNA interference screen against the known histone demethylases and identify a histone H3 lysine 36 (H3K36) demethylase, Jhdm1a, as a key negative regulator of gluconeogenic gene expression. In vivo, silencing of Jhdm1a promotes liver glucose synthesis, while its exogenous expression reduces blood glucose level. Importantly, the regulation of gluconeogenesis by Jhdm1a requires its demethylation activity. Mechanistically, we find that Jhdm1a regulates the expression of a major gluconeogenic regulator, C/EBPα. This is achieved, at least in part, by its USF1-dependent association with the C/EBPα promoter and its subsequent demethylation of dimethylated H3K36 on the C/EBPα locus. Our work provides compelling evidence that links histone demethylation to transcriptional regulation of gluconeogenesis and has important implications for the treatment of diabetes. PMID:22719268

  7. TALE activators regulate gene expression in a position- and strand-dependent manner in mammalian cells.

    Science.gov (United States)

    Uhde-Stone, Claudia; Cheung, Edna; Lu, Biao

    2014-01-24

    Transcription activator-like effectors (TALEs) are a class of transcription factors that are readily programmable to regulate gene expression. Despite their growing popularity, little is known about binding site parameters that influence TALE-mediated gene activation in mammalian cells. We demonstrate that TALE activators modulate gene expression in mammalian cells in a position- and strand-dependent manner. To study the effects of binding site location, we engineered TALEs customized to recognize specific DNA sequences located in either the promoter or the transcribed region of reporter genes. We found that TALE activators robustly activated reporter genes when their binding sites were located within the promoter region. In contrast, TALE activators inhibited the expression of reporter genes when their binding sites were located on the sense strand of the transcribed region. Notably, this repression was independent of the effector domain utilized, suggesting a simple blockage mechanism. We conclude that TALE activators in mammalian cells regulate genes in a position- and strand-dependent manner that is substantially different from gene activation by native TALEs in plants. These findings have implications for optimizing the design of custom TALEs for genetic manipulation in mammalian cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Unions and NGOs positions on the risks and regulation of nanotechnology

    Directory of Open Access Journals (Sweden)

    Noela Invernizzi

    2013-11-01

    Full Text Available This article discusses the perspectives of a number of Non-Governmental Organizations (NGOs and trade unions on the risks and regulation of nanotechnology. In the context of large public and private investments in nanotechnology, and its rapid incorporation into processes and products, these groups have sought to advance their interests through diverse strategies. Their positions are centered in the application of the precautionary principle and include demands for moratoria, more investigation on environmental, health and occupational risks, specific and mandatory regulation, transparent information and broad public participation in the governance of nanotechnology. We show that these civil society organizations are constructing collaborations and alliances and have had some degree of success in placing the issues of risks and regulation into the government´s agendas.

  9. Correlation between Chinese and international energy prices based on a HP filter and time difference analysis

    International Nuclear Information System (INIS)

    He, Yongxiu; Wang, Bing; Wang, Jianhui; Xiong, Wei; Xia, Tian

    2013-01-01

    To establish a reasonable system and mechanism for Chinese energy prices, we use the Granger causality test, Hodrick–Prescott (HP) filter and time difference analysis to research the pricing relationship between Chinese and international energy prices. We find that Chinese and international crude oil prices changed synchronously while Chinese refined oil prices follow the changes of international oil prices with the time difference being about 1 month to 2 months. Further, Australian coal prices Granger causes Chinese coal prices, and there is a high correlation between them. The U.S. electricity price is influenced by the WTI crude oil price, the U.S. gasoline price and the HenryHub gas price. Due to the unreasonable price-setting mechanism and regulation from the central government, China′s terminal market prices for both electricity and natural gas do not reflect the real supply–demand situation. This paper provides quantitative results on the correlation between Chinese and international energy prices to better predict the impact of international energy price fluctuations on China′s domestic energy supply and guide the design of more efficient energy pricing policies. Moreover, it provides references for developing countries to improve their energy market systems and trading, and to coordinate domestic and international energy markets. -- Highlights: •The Hodrick-Prescott filter and time difference analysis are used to research the correlation among energy prices. •Our study finds that the U.S. and British refined oil prices Granger cause the Chinese refined oil price. •Both Chinese and the Australian coal prices play an important role in the international coal market. •The Chinese terminal electric power and terminal natural gas prices are not highly correlated. •The results are useful for guiding the design of more efficient energy pricing policies in China

  10. Response and binding elements for ligand-dependent positive transcription factors integrate positive and negative regulation of gene expression

    International Nuclear Information System (INIS)

    Rosenfeld, M.G.; Glass, C.K.; Adler, S.; Crenshaw, E.B. III; He, X.; Lira, S.A.; Elsholtz, H.P.; Mangalam, H.J.; Holloway, J.M.; Nelson, C.; Albert, V.R.; Ingraham, H.A.

    1988-01-01

    Accurate, regulated initiation of mRNA transcription by RNA polymerase II is dependent on the actions of a variety of positive and negative trans-acting factors that bind cis-acting promoter and enhancer elements. These transcription factors may exert their actions in a tissue-specific manner or function under control of plasma membrane or intracellular ligand-dependent receptors. A major goal in the authors' laboratory has been to identify the molecular mechanisms responsible for the serial activation of hormone-encoding genes in the pituitary during development and the positive and negative regulation of their transcription. The anterior pituitary gland contains phenotypically distinct cell types, each of which expresses unique trophic hormones: adrenocorticotropic hormone, thyroid-stimulating hormone, prolactin, growth hormone, and follicle-stimulating hormone/luteinizing hormone. The structurally related prolactin and growth hormone genes are expressed in lactotrophs and somatotrophs, respectively, with their expression virtually limited to the pituitary gland. The reported transient coexpression of these two structurally related neuroendocrine genes raises the possibility that the prolactin and growth hormone genes are developmentally controlled by a common factor(s)

  11. NUCKS Is a Positive Transcriptional Regulator of Insulin Signaling

    Directory of Open Access Journals (Sweden)

    Beiying Qiu

    2014-06-01

    Full Text Available Although much is known about the molecular players in insulin signaling, there is scant information about transcriptional regulation of its key components. We now find that NUCKS is a transcriptional regulator of the insulin signaling components, including the insulin receptor (IR. Knockdown of NUCKS leads to impaired insulin signaling in endocrine cells. NUCKS knockout mice exhibit decreased insulin signaling and increased body weight/fat mass along with impaired glucose tolerance and reduced insulin sensitivity, all of which are further exacerbated by a high-fat diet (HFD. Genome-wide ChIP-seq identifies metabolism and insulin signaling as NUCKS targets. Importantly, NUCKS is downregulated in individuals with a high body mass index and in HFD-fed mice, and conversely, its levels increase upon starvation. Altogether, NUCKS is a physiological regulator of energy homeostasis and glucose metabolism that works by regulating chromatin accessibility and RNA polymerase II recruitment to the promoters of IR and other insulin pathway modulators.

  12. Influence of the geometrical characteristics of an HpGe detector on its efficiency

    International Nuclear Information System (INIS)

    Vargas, M.J.; Timon, A.F.; Sanchez, D.P.

    2002-01-01

    Computer codes based on Monte Carlo calculations have been extensively developed for the computation of the efficiency in gamma-ray spectrometry. The errors in the specific parameters of the detector due to the lack of precise knowledge of its characteristics usually represent one of the most important sources of inaccuracy in this simulation technique. Influence of several detector parameters on the efficiency for a typical coaxial n-type HpGe detector is presented. Calculations of the full-energy peak efficiencies were performed by means of a Monte Carlo code in the range 122-1836 keV for several types of source configuration: point source, cellulose filter, and two different cylindrical boxes containing a solid matrix of SiO 2 . The detector parameters varied were the crystal diameter, crystal height, diameter of the internal core, and the position of the crystal with respect to the beryllium window. Significant deviations in the efficiency, depending on the source geometry and the photon energy, can be produced by varying only slightly some of the detector parameters. (author)

  13. ClRTL1 Encodes a Chinese Fir RNase III–Like Protein Involved in Regulating Shoot Branching

    Directory of Open Access Journals (Sweden)

    Xia Li

    2015-10-01

    Full Text Available Identification of genes controlling shoot branching is crucial for improving plant architecture and increasing crop yield or biomass. A branching mutant of Chinese fir named “Dugansha” (Cunninghamia lanceolata var. dugan. has been isolated in our laboratory. We chose the cDNA-AFLP technique and an effective strategy to screen genes that potentially regulate shoot branching in Chinese fir using this mutant. An RNase III-like1 cDNA fragment named ClRTL1 was identified as a potential positive regulator. To investigate the function of ClRTL1 in regulating shoot branching, we cloned the full-length cDNA sequence from C. lanceolata (Lamb. Hook, deduced its secondary structure and function, and overexpressed the coding sequence in Arabidopsis. The ClRTL1 cDNA is 1045 bp and comprises an open reading frame of 705 bp. It encodes a protein of 235 amino acids. The deduced secondary structure of the ClRTL1 indicates that it is a mini-RNase III-like protein. The expression analysis and phenotypes of 35S: ClRTL1 in A. thaliana implies that ClRTL1 plays a role in promoting shoot branching in Chinese fir.

  14. Regulation of RNA-dependent RNA polymerase 1 and isochorismate synthase gene expression in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Lydia J R Hunter

    Full Text Available RNA-dependent RNA polymerases (RDRs function in anti-viral silencing in Arabidopsis thaliana and other plants. Salicylic acid (SA, an important defensive signal, increases RDR1 gene expression, suggesting that RDR1 contributes to SA-induced virus resistance. In Nicotiana attenuata RDR1 also regulates plant-insect interactions and is induced by another important signal, jasmonic acid (JA. Despite its importance in defense RDR1 regulation has not been investigated in detail.In Arabidopsis, SA-induced RDR1 expression was dependent on 'NON-EXPRESSER OF PATHOGENESIS-RELATED GENES 1', indicating regulation involves the same mechanism controlling many other SA- defense-related genes, including pathogenesis-related 1 (PR1. Isochorismate synthase 1 (ICS1 is required for SA biosynthesis. In defensive signal transduction RDR1 lies downstream of ICS1. However, supplying exogenous SA to ics1-mutant plants did not induce RDR1 or PR1 expression to the same extent as seen in wild type plants. Analysing ICS1 gene expression using transgenic plants expressing ICS1 promoter:reporter gene (β-glucuronidase constructs and by measuring steady-state ICS1 transcript levels showed that SA positively regulates ICS1. In contrast, ICS2, which is expressed at lower levels than ICS1, is unaffected by SA. The wound-response hormone JA affects expression of Arabidopsis RDR1 but jasmonate-induced expression is independent of CORONATINE-INSENSITIVE 1, which conditions expression of many other JA-responsive genes. Transiently increased RDR1 expression following tobacco mosaic virus inoculation was due to wounding and was not a direct effect of infection. RDR1 gene expression was induced by ethylene and by abscisic acid (an important regulator of drought resistance. However, rdr1-mutant plants showed normal responses to drought.RDR1 is regulated by a much broader range of phytohormones than previously thought, indicating that it plays roles beyond those already suggested in virus

  15. 17 CFR 240.11a-1 - Regulation of floor trading.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Regulation of floor trading... Securities Exchange Act of 1934 Adoption of Floor Trading Regulation (rule 11a-1) § 240.11a-1 Regulation of floor trading. (a) No member of a national securities exchange, while on the floor of such exchange...

  16. Recent advances with quiescent power supply current (I(sub DDQ)) testing at Sandia using the HP82000

    Science.gov (United States)

    Righter, A. W.; Leong, D. J.; Cox, L. B.

    Last year at the HP82000 Users Group Meeting, Sandia National Laboratories gave a presentation on I(sub DDQ) testing. This year, some advances are presented on this testing including DUT board fixturing, external DC PMU measurement, and automatic IDD-All circuit calibration. Implementation is examined more than theory, with results presented from Sandia tests. After a brief summary I(sub DDQ) theory and testing concepts, how the break (hold state) vector and data formatting present a test vector generation concern for the HP82000 is described. Fixturing of the DUT board for both types of I(sub DDQ) measurement is then discussed, along with how the continuity test and test vector generation must be taken into account. Results of a test including continuity, IDD-All and I(sub DDQ) Value measurements is shown. Next, measurement of low current using an external PMU is discussed, including noise considerations, implementation and some test results showing nA-range measurements. A method is presented for automatic calibration of the IDD-All analog comparator circuit using RM BASIC on the HP82000, with implementation and measurement results. Finally, future directions for research in this area is explored.

  17. Kif13b Regulates PNS and CNS Myelination through the Dlg1 Scaffold.

    Directory of Open Access Journals (Sweden)

    Roberta Noseda

    2016-04-01

    Full Text Available Microtubule-based kinesin motors have many cellular functions, including the transport of a variety of cargos. However, unconventional roles have recently emerged, and kinesins have also been reported to act as scaffolding proteins and signaling molecules. In this work, we further extend the notion of unconventional functions for kinesin motor proteins, and we propose that Kif13b kinesin acts as a signaling molecule regulating peripheral nervous system (PNS and central nervous system (CNS myelination. In this process, positive and negative signals must be tightly coordinated in time and space to orchestrate myelin biogenesis. Here, we report that in Schwann cells Kif13b positively regulates myelination by promoting p38γ mitogen-activated protein kinase (MAPK-mediated phosphorylation and ubiquitination of Discs large 1 (Dlg1, a known brake on myelination, which downregulates the phosphatidylinositol 3-kinase (PI3K/v-AKT murine thymoma viral oncogene homolog (AKT pathway. Interestingly, Kif13b also negatively regulates Dlg1 stability in oligodendrocytes, in which Dlg1, in contrast to Schwann cells, enhances AKT activation and promotes myelination. Thus, our data indicate that Kif13b is a negative regulator of CNS myelination. In summary, we propose a novel function for the Kif13b kinesin in glial cells as a key component of the PI3K/AKT signaling pathway, which controls myelination in both PNS and CNS.

  18. Critical Success Factors in Crafting Strategic Architecture for E-Learning at HP University

    Science.gov (United States)

    Sharma, Kunal; Pandit, Pallvi; Pandit, Parul

    2011-01-01

    Purpose: The purpose of this paper is to outline the critical success factors for crafting a strategic architecture for e-learning at HP University. Design/methodology/approach: A descriptive survey type of research design was used. An empirical study was conducted on students enrolled with the International Centre for Distance and Open Learning…

  19. BRCA1-IRIS regulates cyclin D1 expression in breast cancer cells

    International Nuclear Information System (INIS)

    Nakuci, Enkeleda; Mahner, Sven; DiRenzo, James; ElShamy, Wael M.

    2006-01-01

    The regulator of cell cycle progression, cyclin D1, is up-regulated in breast cancer cells; its expression is, in part, dependent on ERα signaling. However, many ERα-negative tumors and tumor cell lines (e.g., SKBR3) also show over-expression of cyclin D1. This suggests that, in addition to ERα signaling, cyclin D1 expression is under the control of other signaling pathways; these pathways may even be over-expressed in the ERα-negative cells. We previously noticed that both ERα-positive and -negative cell lines over-express BRCA1-IRIS mRNA and protein. Furthermore, the level of over-expression of BRCA1-IRIS in ERα-negative cell lines even exceeded its over-expression level in ERα-positive cell lines. In this study, we show that: (1) BRCA1-IRIS forms complex with two of the nuclear receptor co-activators, namely, SRC1 and SRC3 (AIB1) in an ERα-independent manner. (2) BRCA1-IRIS alone, or in connection with co-activators, is recruited to the cyclin D1 promoter through its binding to c-Jun/AP1 complex; this binding activates the cyclin D1 expression. (3) Over-expression of BRCA1-IRIS in breast cells over-activates JNK/c-Jun; this leads to the induction of cyclin D1 expression and cellular proliferation. (4) BRCA1-IRIS activation of JNK/c-Jun/AP1 appears to account for this, because in cells that were depleted from BRCA1-IRIS, JNK remained inactive. However, depletion of SRC1 or SRC3 instead reduced c-Jun expression. Our data suggest that this novel signaling pathway links BRCA1-IRIS to cellular proliferation through c-Jun/AP1 nuclear pathway; finally, this culminates in the increased expression of the cyclin D1 gene

  20. Rapid and reversible epigenome editing by endogenous chromatin regulators.

    Science.gov (United States)

    Braun, Simon M G; Kirkland, Jacob G; Chory, Emma J; Husmann, Dylan; Calarco, Joseph P; Crabtree, Gerald R

    2017-09-15

    Understanding the causal link between epigenetic marks and gene regulation remains a central question in chromatin biology. To edit the epigenome we developed the FIRE-Cas9 system for rapid and reversible recruitment of endogenous chromatin regulators to specific genomic loci. We enhanced the dCas9-MS2 anchor for genome targeting with Fkbp/Frb dimerizing fusion proteins to allow chemical-induced proximity of a desired chromatin regulator. We find that mSWI/SNF (BAF) complex recruitment is sufficient to oppose Polycomb within minutes, leading to activation of bivalent gene transcription in mouse embryonic stem cells. Furthermore, Hp1/Suv39h1 heterochromatin complex recruitment to active promoters deposits H3K9me3 domains, resulting in gene silencing that can be reversed upon washout of the chemical dimerizer. This inducible recruitment strategy provides precise kinetic information to model epigenetic memory and plasticity. It is broadly applicable to mechanistic studies of chromatin in mammalian cells and is particularly suited to the analysis of endogenous multi-subunit chromatin regulator complexes.Understanding the link between epigenetic marks and gene regulation requires the development of new tools to directly manipulate chromatin. Here the authors demonstrate a Cas9-based system to recruit chromatin remodelers to loci of interest, allowing rapid, reversible manipulation of epigenetic states.

  1. HvDep1 Is a Positive Regulator of Culm Elongation and Grain Size in Barley and Impacts Yield in an Environment-Dependent Manner.

    Directory of Open Access Journals (Sweden)

    Toni Wendt

    Full Text Available Heterotrimeric G proteins are intracellular membrane-attached signal transducers involved in various cellular processes in both plants and animals. They consist of three subunits denoted as α, β and γ. The γ-subunits of the so-called AGG3 type, which comprise a transmembrane domain, are exclusively found in plants. In model species, these proteins have been shown to participate in the control of plant height, branching and seed size and could therefore impact the harvestable yield of various crop plants. Whether AGG3-type γ-subunits influence yield in temperate cereals like barley and wheat remains unknown. Using a transgenic complementation approach, we show here that the Scottish malting barley cultivar (cv. Golden Promise carries a loss-of-function mutation in HvDep1, an AGG3-type subunit encoding gene that positively regulates culm elongation and seed size in barley. Somewhat intriguingly, agronomic field data collected over a 12-year period reveals that the HvDep1 loss-of-function mutation in cv. Golden Promise has the potential to confer either a significant increase or decrease in harvestable yield depending on the environment. Our results confirm the role of AGG3-type subunit-encoding genes in shaping plant architecture, but interestingly also indicate that the impact HvDep1 has on yield in barley is both genotypically and environmentally sensitive. This may explain why widespread exploitation of variation in AGG3-type subunit-encoding genes has not occurred in temperate cereals while in rice the DEP1 locus is widely exploited to improve harvestable yield.

  2. In vivo dynamics of GFRα1-positive spermatogonia stimulated by GDNF signals using a bead transplantation assay

    Energy Technology Data Exchange (ETDEWEB)

    Uchida, Aya; Kishi, Kasane; Aiyama, Yoshimi; Miura, Kento [Department of Veterinary Anatomy, The University of Tokyo, Yayoi, Tokyo, 113-8657 (Japan); Takase, Hinako M.; Suzuki, Hitomi; Kanai-Azuma, Masami [Department of Experimental Animal Model for Human Disease, Tokyo Medical and Dental University, Tokyo, 113-8510 (Japan); Iwamori, Tokuko [Center of Biomedical Research, Kyusyu University, Fukuoka, 812-8582 (Japan); Kurohmaru, Masamichi; Tsunekawa, Naoki [Department of Veterinary Anatomy, The University of Tokyo, Yayoi, Tokyo, 113-8657 (Japan); Kanai, Yoshiakira, E-mail: aykanai@mail.ecc.u-tokyo.ac.jp [Department of Veterinary Anatomy, The University of Tokyo, Yayoi, Tokyo, 113-8657 (Japan)

    2016-08-05

    In mouse testes, spermatogonial stem cells (SSCs), a subpopulation of GFRα1 (GDNF family receptor-α1)-positive spermatogonia, are widely distributed along the convoluted seminiferous tubules. The proliferation and differentiation of the SSCs are regulated in part by local expression of GDNF (glial cell-derived neurotorphic factor), one of major niche factors for SSCs. However, the in vivo dynamics of the GDNF-stimulated GFRα1-positive spermatogonia remains unclear. Here, we developed a simple method for transplanting DiI-labeled and GDNF-soaked beads into the mouse testicular interstitium. By using this method, we examined the dynamics of GFRα1-positive spermatogonia in the tubular walls close to the transplanted GDNF-soaked beads. The bead-derived GDNF signals were able to induce the stratified aggregate formation of GFRα1-positive undifferentiated spermatogonia by day 3 post-transplantation. Each aggregate consisted of tightly compacted A{sub single} and marginal A{sub paired}–A{sub aligned} GFRα1-positive spermatogonia and was surrounded by A{sub aligned} GFRα1-negative spermatogonia at more advanced stages. These data not only provide in vivo evidence for the inductive roles of GDNF in forming a rapid aggregation of GFRα1-positive spermatogonia but also indicate the usefulness of this in vivo assay system of various growth factors for the stem/progenitor spermatogonia in mammalian spermatogenesis. - Highlights: • A novel bead transplantation assay was developed to examine the in vivo effects of growth factors on spermatogonia. • A rapid aggregation of GFRα1-positive spermatogonia was induced by the transplanted GDNF-soaked beads. • Tightly-compacted A{sub single} and marginal A{sub paired}–A{sub aligned} spermatogonia were formed in each GFRα1-positive aggregate.

  3. The Spectral/hp-Finite Element Method for Partial Differential Equations

    DEFF Research Database (Denmark)

    Engsig-Karup, Allan Peter

    2009-01-01

    dimensions. In the course the chosen programming environment is Matlab, however, this is by no means a necessary requirement. The mathematical level needed to grasp the details of this set of notes requires an elementary background in mathematical analysis and linear algebra. Each chapter is supplemented......This set of lecture notes provides an elementary introduction to both the classical Finite Element Method (FEM) and the extended Spectral/$hp$-Finite Element Method for solving Partial Differential Equations (PDEs). Many problems in science and engineering can be formulated mathematically...

  4. Activation of TGF-β1-CD147 positive feedback loop in hepatic stellate cells promotes liver fibrosis.

    Science.gov (United States)

    Li, Hai-Yan; Ju, Di; Zhang, Da-Wei; Li, Hao; Kong, Ling-Min; Guo, Yanhai; Li, Can; Wang, Xi-Long; Chen, Zhi-Nan; Bian, Huijie

    2015-11-12

    Activation of hepatic stellate cells (HSCs) by transforming growth factor-β1 (TGF-β1) initiates HBV-associated fibrogenesis. The mechanism of TGF-β1 modulating HSC activation is not fully uncovered. We hypothesized a positive feedback signaling loop of TGF-β1-CD147 promoting liver fibrogenesis by activation of HSCs. Human HSC cell line LX-2 and spontaneous liver fibrosis model derived from HBV transgenic mice were used to evaluate the activation of molecules in the signaling loop. Wound healing and cell contraction assay were performed to detect the CD147-overexpressed HSC migration and contraction. The transcriptional regulation of CD147 by TGF-β1/Smad4 was determined using dual-luciferase reporter assay and chromatin immunoprecipitation. We found that a positive reciprocal regulation between TGF-β1 and CD147 mediated HSC activation. CD147 over-expression promoted HSC migration and accelerated TGF-β1-induced cell contraction. Phosphorylation of Smad2 and Smad3 in cooperation with Smad4 mediated the TGF-β1-regulated CD147 expression. Smad4 activated the transcription by direct interaction with CD147 promoter. Meanwhile, CD147 modulated the activated phenotype of HSCs through the ERK1/2 and Sp1 which up-regulated α-SMA, collagen I, and TGF-β1 synthesis. These findings indicate that TGF-β1-CD147 loop plays a key role in regulating the HSC activation and combination of TGF-β receptor inhibitor and anti-CD147 antibody might be promised to reverse fibrogenesis.

  5. Comparative study in LTC Combustion between a short HP EGR loop without cooler and a variable lift and duration system

    Energy Technology Data Exchange (ETDEWEB)

    Bression, Guillaume; Pacaud, Pierre; Soleri, Dominique; Cessou, Jerome [IFP (France); Azoulay, David [Renault Powertrain Div. (France); Lawrence, David [Mechadyne (United Kingdom); Doradoux, Laurent; Guerrassi, Noureddine [Delphi Diesel Systems (France)

    2008-07-01

    In order to reach future Diesel emission standards such as Euro 6 or Tier 2 Bin 5, NO{sub x} emissions need to be dramatically reduced. Advanced technologies and engine settings such as higher EGR rates, reduced compression ratio, EGR cooler and low-pressure EGR loop - depending on vehicle application - may help to reach this target whilst maintaining low CO{sub 2} emissions and fuel consumption. However, the resulting low combustion temperatures and the low air-fuel ratios lead to a significant increase in HC and CO emissions, especially during the start-up phase prior to catalyst light-off. Moreover, high levels of EGR make transient operation even more difficult. So HC-CO emissions and EGR transient operation represent two key issues that could limit the extension of this alternative combustion mode. Consequently, an in-depth investigation of a variable lift and duration (VLD) system was performed to overcome these problems on a 4-cylinder engine, which was also equipped with a dual HP-LP EGR loop. The VLD system tested in this paper produces a variable camshaft-operated exhaust valve re-opening, which is controlled by a hydraulic rotary actuator, ensuring quick and accurate regulation of the internal gas recirculation (IGR). By increasing gas temperature in the combustion chamber, this advanced technology allows us to reduce HC-CO emissions by 50% under 3 bar BMEP. Although efficient, this technology has to be compared with other solutions from a cost-to-value point of view. The aim of this paper is firstly to compare the double lift exhaust system with a short route high-performance EGR loop without cooler by quantifying their respective gains on steady state points of the NEDC cycle, then by evaluating their potential performances during transient conditions. With the short-route EGR, the potential in HC-CO emission reduction remains significant on a large scale of engine temperatures representative of engine warm up. However, the VLD system allows us to

  6. ROCK1-directed basement membrane positioning coordinates epithelial tissue polarity.

    Science.gov (United States)

    Daley, William P; Gervais, Elise M; Centanni, Samuel W; Gulfo, Kathryn M; Nelson, Deirdre A; Larsen, Melinda

    2012-01-01

    The basement membrane is crucial for epithelial tissue organization and function. However, the mechanisms by which basement membrane is restricted to the basal periphery of epithelial tissues and the basement membrane-mediated signals that regulate coordinated tissue organization are not well defined. Here, we report that Rho kinase (ROCK) controls coordinated tissue organization by restricting basement membrane to the epithelial basal periphery in developing mouse submandibular salivary glands, and that ROCK inhibition results in accumulation of ectopic basement membrane throughout the epithelial compartment. ROCK-regulated restriction of PAR-1b (MARK2) localization in the outer basal epithelial cell layer is required for basement membrane positioning at the tissue periphery. PAR-1b is specifically required for basement membrane deposition, as inhibition of PAR-1b kinase activity prevents basement membrane deposition and disrupts overall tissue organization, and suppression of PAR-1b together with ROCK inhibition prevents interior accumulations of basement membrane. Conversely, ectopic overexpression of wild-type PAR-1b results in ectopic interior basement membrane deposition. Significantly, culture of salivary epithelial cells on exogenous basement membrane rescues epithelial organization in the presence of ROCK1 or PAR-1b inhibition, and this basement membrane-mediated rescue requires functional integrin β1 to maintain epithelial cell-cell adhesions. Taken together, these studies indicate that ROCK1/PAR-1b-dependent regulation of basement membrane placement is required for the coordination of tissue polarity and the elaboration of tissue structure in the developing submandibular salivary gland.

  7. A super-family of transcriptional activators regulates bacteriophage packaging and lysis in Gram-positive bacteria

    Science.gov (United States)

    Quiles-Puchalt, Nuria; Tormo-Más, María Ángeles; Campoy, Susana; Toledo-Arana, Alejandro; Monedero, Vicente; Lasa, Íñigo; Novick, Richard P.; Christie, Gail E.; Penadés, José R.

    2013-01-01

    The propagation of bacteriophages and other mobile genetic elements requires exploitation of the phage mechanisms involved in virion assembly and DNA packaging. Here, we identified and characterized four different families of phage-encoded proteins that function as activators required for transcription of the late operons (morphogenetic and lysis genes) in a large group of phages infecting Gram-positive bacteria. These regulators constitute a super-family of proteins, here named late transcriptional regulators (Ltr), which share common structural, biochemical and functional characteristics and are unique to this group of phages. They are all small basic proteins, encoded by genes present at the end of the early gene cluster in their respective phage genomes and expressed under cI repressor control. To control expression of the late operon, the Ltr proteins bind to a DNA repeat region situated upstream of the terS gene, activating its transcription. This involves the C-terminal part of the Ltr proteins, which control specificity for the DNA repeat region. Finally, we show that the Ltr proteins are the only phage-encoded proteins required for the activation of the packaging and lysis modules. In summary, we provide evidence that phage packaging and lysis is a conserved mechanism in Siphoviridae infecting a wide variety of Gram-positive bacteria. PMID:23771138

  8. Distinct Clinicopathological Features and Prognosis of Helicobacter pylori Negative Gastric Cancer.

    Directory of Open Access Journals (Sweden)

    Kun-Feng Tsai

    Full Text Available Whether the characteristics and prognosis of gastric cancer (GC are different in patients with and without Helicobacter pylori (HP remains controversial. The definitions of HP status in patients with atrophic gastritis but negative tests for HP are heterogeneous. We aimed to assess the impact of HP on the prognosis of GC using different definitions.From 1998 Nov to 2011 Jul, five hundred and sixty-seven consecutive patients with GC were included. HP status was determined by serology and histology. Patients with any positive test were defined as HP infection. Patients without HP infection whose serum pepsinogen (PG I <70 ng/dl and PG I/II ratio < 3.0 were defined as atrophic gastritis and they were categorized into model 1: HP positive; model 2: HP negative; and model 3: exclusion of these patients.We found four characteristics of HP negative GC in comparison to HP positive GC: (1 higher proportion of the proximal tumor location (24.0%, P = 0.004, (2 more diffuse histologic type (56.1%, p = 0.008, (3 younger disease onset (58.02 years, p = 0.008 and (4 more stage IV disease (40.6%, p = 0.03. Patients with negative HP had worse overall survival (24.0% vs. 35.8%, p = 0.035. In Cox regression models, the negative HP status is an independent poor prognostic factor (HR: 1.34, CI:1.04-1.71, p = 0.019 in model 1, especially in stage I, II and III patients (HR: 1.62; CI:1.05-2.51,p = 0.026.We found the distinct characteristics of HP negative GC. The prognosis of HP negative GC was poor.

  9. The ASK1 gene regulates B function gene expression in cooperation with UFO and LEAFY in Arabidopsis.

    Science.gov (United States)

    Zhao, D; Yu, Q; Chen, M; Ma, H

    2001-07-01

    The Arabidopsis floral regulatory genes APETALA3 (AP3) and PISTILLATA (PI) are required for the B function according to the ABC model for floral organ identity. AP3 and PI expression are positively regulated by the LEAFY (LFY) and UNUSUAL FLORAL ORGANS (UFO) genes. UFO encodes an F-box protein, and we have shown previously that UFO genetically interacts with the ASK1 gene encoding a SKP1 homologue; both the F-box containing protein and SKP1 are subunits of ubiquitin ligases. We show here that the ask1-1 mutation can enhance the floral phenotypes of weak lfy and ap3 mutants; therefore, like UFO, ASK1 also interacts with LFY and AP3 genetically. Furthermore, our results from RNA in situ hybridizations indicate that ASK1 regulates early AP3 and PI expression. These results support the idea that UFO and ASK1 together positively regulate AP3 and PI expression. We propose that the UFO and ASK1 proteins are components of a ubiquitin ligase that mediates the proteolysis of a repressor of AP3 and PI expression. Our genetic studies also indicate that ASK1 and UFO play a role in regulating the number of floral organ primordia, and we discuss possible mechanisms for such a regulation.

  10. The intercomparison of 137Cs irradiator output measurement and personal dose equivalent, Hp(10), using TLD and film

    International Nuclear Information System (INIS)

    Nazaroh; Susetyo Trijoko; Sri Inang Sunaryati

    2010-01-01

    Intercomparison of output measurement of 137 Cs irradiator and personal dose equivalent, Hp(10) using TLD and film have been carried out in the year of 2006 to 2008. According to IAEA recommendation, intercomparison is one of audit activities but it is performed in the spirit of collaboration and support rather than in the spirit of inspection. The aim of intercomparison of output measurement of 137 Cs irradiator is to verify the dose stated by the participant laboratories. Intercomparison is also to assess the competency of the participant, to keep traceability and consistency of measurement result, to assure that instrument work correctly and the result of evaluation was in agreement, and also for fulfilling one of the clauses of ISO-17025-2005. Besides that, this intercomparison aimed to facilitate link between the system and members of national measurement and transfer of experience in measurement technique and dose evaluation of radiation. The benefit of intercomparison is important among others as tests of proficiency in dose evaluation or measurement, upgrading quality of service and for obeying supervisor body legislation (BAPETEN). TLD was used as a means of output 137 Cs irradiator measurement, whereas film and TLD were used for dose intercomparison. This paper presented result of intercomparison of output measurement and evaluation of personal dose equivalent, Hp(10) in the year of 2006 to 2008 followed by 6 participants: Balai Pengamanan Fasilitas Kesehatan (BPFK) Jakarta, Medan, Surabaya, Makasar, PTLR and Laboratory of Keselamatan dan Kesehatan Lingkungan (KKL)-PTKMR BATAN. In this intercomparison, the dose of TLD stated by participant were compared with the dose measured by Radiation Metrology Laboratory (LMR), and the results showed the differences were within 10 %, so it was satisfied. The results of intercomparison of personal dose equivalent, Hp(10) were evaluated based on ISO/IEC Guide 43-1, 1997 analysis and expressed as E n . The values of E n

  11. HDAC1 regulates the proliferation of radial glial cells in the developing Xenopus tectum.

    Directory of Open Access Journals (Sweden)

    Yi Tao

    Full Text Available In the developing central nervous system (CNS, progenitor cells differentiate into progeny to form functional neural circuits. Radial glial cells (RGs are a transient progenitor cell type that is present during neurogenesis. It is thought that a combination of neural trophic factors, neurotransmitters and electrical activity regulates the proliferation and differentiation of RGs. However, it is less clear how epigenetic modulation changes RG proliferation. We sought to explore the effect of histone deacetylase (HDAC activity on the proliferation of RGs in the visual optic tectum of Xenopus laevis. We found that the number of BrdU-labeled precursor cells along the ventricular layer of the tectum decrease developmentally from stage 46 to stage 49. The co-labeling of BrdU-positive cells with brain lipid-binding protein (BLBP, a radial glia marker, showed that the majority of BrdU-labeled cells along the tectal midline are RGs. BLBP-positive cells are also developmentally decreased with the maturation of the brain. Furthermore, HDAC1 expression is developmentally down-regulated in tectal cells, especially in the ventricular layer of the tectum. Pharmacological blockade of HDACs using Trichostatin A (TSA or Valproic acid (VPA decreased the number of BrdU-positive, BLBP-positive and co-labeling cells. Specific knockdown of HDAC1 by a morpholino (HDAC1-MO decreased the number of BrdU- and BLBP-labeled cells and increased the acetylation level of histone H4 at lysine 12 (H4K12. The visual deprivation-induced increase in BrdU- and BLBP-positive cells was blocked by HDAC1 knockdown at stage 49 tadpoles. These data demonstrate that HDAC1 regulates radial glia cell proliferation in the developing optical tectum of Xenopus laevis.

  12. Regulatory RNAs in Bacillus subtilis: a Gram-Positive Perspective on Bacterial RNA-Mediated Regulation of Gene Expression

    Science.gov (United States)

    Mars, Ruben A. T.; Nicolas, Pierre; Denham, Emma L.

    2016-01-01

    SUMMARY Bacteria can employ widely diverse RNA molecules to regulate their gene expression. Such molecules include trans-acting small regulatory RNAs, antisense RNAs, and a variety of transcriptional attenuation mechanisms in the 5′ untranslated region. Thus far, most regulatory RNA research has focused on Gram-negative bacteria, such as Escherichia coli and Salmonella. Hence, there is uncertainty about whether the resulting insights can be extrapolated directly to other bacteria, such as the Gram-positive soil bacterium Bacillus subtilis. A recent study identified 1,583 putative regulatory RNAs in B. subtilis, whose expression was assessed across 104 conditions. Here, we review the current understanding of RNA-based regulation in B. subtilis, and we categorize the newly identified putative regulatory RNAs on the basis of their conservation in other bacilli and the stability of their predicted secondary structures. Our present evaluation of the publicly available data indicates that RNA-mediated gene regulation in B. subtilis mostly involves elements at the 5′ ends of mRNA molecules. These can include 5′ secondary structure elements and metabolite-, tRNA-, or protein-binding sites. Importantly, sense-independent segments are identified as the most conserved and structured potential regulatory RNAs in B. subtilis. Altogether, the present survey provides many leads for the identification of new regulatory RNA functions in B. subtilis. PMID:27784798

  13. Regulatory RNAs in Bacillus subtilis: a Gram-Positive Perspective on Bacterial RNA-Mediated Regulation of Gene Expression.

    Science.gov (United States)

    Mars, Ruben A T; Nicolas, Pierre; Denham, Emma L; van Dijl, Jan Maarten

    2016-12-01

    Bacteria can employ widely diverse RNA molecules to regulate their gene expression. Such molecules include trans-acting small regulatory RNAs, antisense RNAs, and a variety of transcriptional attenuation mechanisms in the 5' untranslated region. Thus far, most regulatory RNA research has focused on Gram-negative bacteria, such as Escherichia coli and Salmonella. Hence, there is uncertainty about whether the resulting insights can be extrapolated directly to other bacteria, such as the Gram-positive soil bacterium Bacillus subtilis. A recent study identified 1,583 putative regulatory RNAs in B. subtilis, whose expression was assessed across 104 conditions. Here, we review the current understanding of RNA-based regulation in B. subtilis, and we categorize the newly identified putative regulatory RNAs on the basis of their conservation in other bacilli and the stability of their predicted secondary structures. Our present evaluation of the publicly available data indicates that RNA-mediated gene regulation in B. subtilis mostly involves elements at the 5' ends of mRNA molecules. These can include 5' secondary structure elements and metabolite-, tRNA-, or protein-binding sites. Importantly, sense-independent segments are identified as the most conserved and structured potential regulatory RNAs in B. subtilis. Altogether, the present survey provides many leads for the identification of new regulatory RNA functions in B. subtilis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  14. The dominant allele Aft induces a shift from flavonol to anthocyanin production in response to UV-B radiation in tomato fruit.

    Science.gov (United States)

    Catola, Stefano; Castagna, Antonella; Santin, Marco; Calvenzani, Valentina; Petroni, Katia; Mazzucato, Andrea; Ranieri, Annamaria

    2017-08-01

    The introgression of the A ft allele into domesticated tomato induced a shift from flavonol to anthocyanin production in response to UV-B radiation, while the hp - 1 allele negatively influenced the response of flavonoid biosynthesis to UV-B. Introgression of the dominant allele Anthocyanin fruit (Aft) from Solanum chilense induces anthocyanin accumulation in the peel of tomato (Solanum lycopersicum L.) fruit. UV-B radiation can influence plant secondary metabolism regulating the expression of several genes, among which those involved in flavonoid biosynthesis. Here, we investigated whether post-harvest UV-B treatment could up-regulate flavonoid production in tomato fruits and whether the Aft allele could affect flavonoid biosynthesis under UV-B radiation. Mature green fruits of an anthocyanin-rich tomato mutant line (SA206) and of its wild-type reference, cv. Roma, were daily subjected to post-harvest UV-B treatment until full ripening. Up-regulation of CHS and CHI transcription by UV-B treatment induced flavonoid accumulation in the peel of cv. Roma. Conversely, UV-B decreased the total flavonoid content and CHS transcript levels in the SA206 peel. SA206 being a double mutant containing also hp-1 allele, we investigated also the behavior of hp-1 fruit. The decreased peel flavonoid accumulation and gene transcription in response to UV-B suggest that hp-1 allele is involved in the marked down-regulation of the flavonoid biosynthesis observed in SA206 fruit. Interestingly, in SA206, UV-B radiation promoted the synthesis of delphinidin, petunidin, and malvidin by increasing F3'5'H and DFR transcription, but it decreased rutin production, suggesting a switch from flavonols to anthocyanins. Finally, although UV-B radiation does not reach the inner fruit tissues, it down-regulated flavonoid biosynthesis in the flesh of both genotypes. This study provides, for the first time, evidence that the presence of the functional Aft allele, under UV-B radiation, redirects

  15. Endogenous retrovirus EAV-HP linked to blue egg phenotype in Mapuche fowl.

    Science.gov (United States)

    Wragg, David; Mwacharo, Joram M; Alcalde, José A; Wang, Chen; Han, Jian-Lin; Gongora, Jaime; Gourichon, David; Tixier-Boichard, Michèle; Hanotte, Olivier

    2013-01-01

    Oocyan or blue/green eggshell colour is an autosomal dominant trait found in native chickens (Mapuche fowl) of Chile and in some of their descendants in European and North American modern breeds. We report here the identification of an endogenous avian retroviral (EAV-HP) insertion in oocyan Mapuche fowl and European breeds. Sequencing data reveals 100% retroviral identity between the Mapuche and European insertions. Quantitative real-time PCR analysis of European oocyan chicken indicates over-expression of the SLCO1B3 gene (P<0.05) in the shell gland and oviduct. Predicted transcription factor binding sites in the long terminal repeats (LTR) indicate AhR/Ar, a modulator of oestrogen, as a possible promoter/enhancer leading to reproductive tissue-specific over-expression of the SLCO1B3 gene. Analysis of all jungle fowl species Gallus sp. supports the retroviral insertion to be a post-domestication event, while identical LTR sequences within domestic chickens are in agreement with a recent de novo mutation.

  16. Sp1-CD147 positive feedback loop promotes the invasion ability of ovarian cancer.

    Science.gov (United States)

    Zhao, Jing; Ye, Wei; Wu, Juan; Liu, Lijuan; Yang, Lina; Gao, Lu; Chen, Biliang; Zhang, Fanglin; Yang, Hong; Li, Yu

    2015-07-01

    CD147 is a novel cancer biomarker that has been confirmed to be overexpressed in ovarian carcinoma, which is significantly associated with poor prognosis. Although the Sp1 protein regulates the expression level of CD147, it remains unclear whether Sp1 phosphorylation plays a role in this regulation. A dual-luciferase assay revealed that T453 and T739 mutations decreased the activity of Sp1 binding to the promoter of CD147, followed by a decrease in CD147 mRNA and protein expression. Western blot analysis showed that CD147 promoted Sp1 phosphorylation at T453 and T739 through the PI3K/AKT and MAPK/ERK pathways. In addition, blocking the Sp1-CD147 positive feedback loop reduced the invasion ability of HO-8910pm cells. Immunohistochemical staining showed that the components of the feedback loop were overexpressed in ovarian cancer tissues. The correlation analysis revealed a significant correlation between phospho-Sp1 (T453), phospho-Sp1 (T739) and CD147 expression levels, with correlation coefficients of r=0.477 and r=0.461, respectively. Collectively, our results suggest that a Sp1-CD147 positive feedback loop plays a critical role in the invasion ability of ovarian cancer cells.

  17. Emotion regulation strategies mediate the associations of positive and negative affect to upper extremity physical function.

    Science.gov (United States)

    Talaei-Khoei, Mojtaba; Nemati-Rezvani, Hora; Fischerauer, Stefan F; Ring, David; Chen, Neal; Vranceanu, Ana-Maria

    2017-05-01

    The Gross process model of emotion regulation holds that emotion-eliciting situations (e.g. musculoskeletal illness) can be strategically regulated to determine the final emotional and behavioral response. Also, there is some evidence that innate emotional traits may predispose an individual to a particular regulating coping style. We enrolled 107 patients with upper extremity musculoskeletal illness in this cross-sectional study. They completed self-report measures of positive and negative affect, emotion regulation strategies (cognitive reappraisal and expressive suppression), upper extremity physical function, pain intensity, and demographics. We used Preacher and Hayes' bootstrapping approach to process analysis to infer the direct effect of positive and negative affect on physical function as well as their indirect effects through activation of emotion regulation strategies. Negative affect was associated with decreased physical function. The association was partly mediated by expressive suppression (b (SE)=-.10 (.05), 95% BCa CI [-.21, -.02]). Positive affect was associated with increased physical function. Cognitive reappraisal partially mediated this association (b (SE)=.11 (.05), 95% BCa CI [.03, .24]). After controlling for pain intensity, the ratio of the mediated effect to total effect grew even larger in controlled model comparing to uncontrolled model (33% vs. 26% for expressive suppression and 32% vs. 30% for cognitive reappraisal). The relationships between affect, emotion regulation strategies and physical function appear to be more dependent on the emotional response to an orthopedic condition rather than the intensity of the nociceptive stimulation of the pain. Findings support integration of emotion regulation training in skill-based psychotherapy in this population to mitigate the effect of negative affect and enhance the influence of positive affect on physical function. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. HP-CsB{sub 5}O{sub 8}. Synthesis and characterization of an outstanding borate exhibiting the simultaneous linkage of all structural units of borates

    Energy Technology Data Exchange (ETDEWEB)

    Sohr, Gerhard; Huppertz, Hubert [Institut fuer Allgemeine, Anorganische und Theoretische Chemie, Leopold-Franzens-Universitaet Innsbruck (Austria); Toebbens, Daniel M. [Helmholtz-Zentrum Berlin fuer Materialien und Energie GmbH, Berlin (Germany); Schmedt auf der Guenne, Joern [Department fuer Chemie/Biologie, Universitaet Siegen (Germany)

    2014-12-15

    The new cesium pentaborate HP-CsB{sub 5}O{sub 8} is synthesized under high-pressure/high-temperature conditions of 6 GPa and 900 C in a Walker-type multianvil apparatus. The compound crystallizes in the orthorhombic space group Pnma (Z=4) with the parameters a=789.7(1), b=961.2(1), c=836.3(1) pm, V=0.6348(1) nm{sup 3}, R{sub 1}=0.0359 and wR{sub 2}=0.0440 (all data). The new structure type of HP-CsB{sub 5}O{sub 8} exhibits the simultaneous linkage of trigonal BO{sub 3} groups, corner-sharing BO{sub 4} tetrahedra, and edge-sharing BO{sub 4} tetrahedra including the presence of threefold-coordinated oxygen atoms. With respect to the rich structural chemistry of borates, HP-CsB{sub 5}O{sub 8} is the second structure type possessing this outstanding combination of the main structural units of borates in one compound. The structure consists of corrugated chains of corner- and edge-sharing BO{sub 4} tetrahedra interconnected through BO{sub 3} groups forming octagonal channels. Inside these channels, cesium is 13+3-fold coordinated by oxygen atoms. {sup 11}B MQMAS NMR spectra are analyzed to estimate the isotropic chemical shift values and quadrupolar parameters. IR and Raman spectra are obtained and compared to the calculated vibrational frequencies at the Γ-point. The high-temperature behavior is examined by means of temperature-programmed powder diffraction. (copyright 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  19. Peak {sup 14}CO{sub 2} excretion, symptoms and eradication of H.Pylori (HP) in patients with duodenal ulcer (DU)

    Energy Technology Data Exchange (ETDEWEB)

    Batholomeusz, F.D.L.; Bellon, M. [Royal Adelaide Hospital, Adelaide, SA (Australia). Department of Nuclear Medicine

    1997-12-01

    Full text: Many factors including drug efficacy, compliance and antibiotic resistance may influence HP eradication rates. The {sup 14}C urea breath test is a sensitive method of confirming HP colonisation and eradication. The aim was to study the relationships between the peak {sup 14}CO{sub 2} counts on the breath test prior to treatment, smoking and HP eradication, and to assess if persistent or recurrent symptoms implied failure of eradication. 117 patients with DU and HP colonisation proved on biopsy or rapid urease test who underwent {sup 14}C urea breath tests at least one month after eradication treatment was ceased were studied (69 male, 48 female, mean age 41, range 26-87 y). Questionnaire assessment of treatment regimen, smoking history and dyspeptic symptoms was made at the time of the breath test. A sub-group of 43 patients who had pre- and post-treatment breath tests was studied to assess if high peak {sup 14}CO{sub 2} counts on the pre-treatment breath test related to treatment success. The mean peak initial {sup 14}CO{sub 2} excretion in those who were treated successfully was 4187 (+ 472) counts/min and for failures 4817 (+739) counts/min (p 0.24). Dyspeptic symptoms were present in 36% of patients treated successfully and 37% where treatment failed. The eradication rate for the 56 smokers was 75 per cent, and the 61 non-smokers 83%. (p>0.2) High {sup 14}CO{sub 2} excretion on the initial {sup 14}C urea breath test and smoking are not associated with a significantly lower rate of HP eradication and the presence of dyspepsia is not a good indicator of persistent infection

  20. PID position regulation in one-degree-of-freedom Euler-Lagrange systems actuated by a PMSM

    Science.gov (United States)

    Verastegui-Galván, J.; Hernández-Guzmán, V. M.; Orrante-Sakanassi, J.

    2018-02-01

    This paper is concerned with position regulation in one-degree-of-freedom Euler-Lagrange Systems. We consider that the mechanical subsystem is actuated by a permanent magnet synchronous motor (PMSM). Our proposal consists of a Proportional-Integral-Derivative (PID) controller for the mechanical subsystem and a slight variation of field oriented control for the PMSM. We take into account the motor electric dynamics during the stability analysis. We present, for the first time, a global asymptotic stability proof for such a control scheme without requiring the mechanical subsystem to naturally possess viscous friction. Finally, as a corollary of our main result we prove global asymptotic stability for output feedback PID regulation of one-degree-of-freedom Euler-Lagrange systems when generated torque is considered as the system input, i.e. when the electric dynamics of PMSM's is not taken into account.

  1. Structure of trihydrated rare-earth acid diphosphates LnHP2O7·3H2O (Ln=La, Er)

    International Nuclear Information System (INIS)

    Ben Moussa, S.; Ventemillas, S.; Cabeza, A.; Gutierrez-Puebla, E.; Sanz, J.

    2004-01-01

    In trihydrated lanthanum acid-diphosphates LnHP 2 O 7 ·3H 2 O, prepared from acid LnCl 3 and Na 4 P 2 O 7 solutions (pH=1), two crystal forms were obtained. Layered structures of two representative members of this family have been determined by single-crystal X-ray diffraction (XRD) technique. In the case of orthorhombic LaHP 2 O 7 ·3H 2 O (type I), lanthanum cations are ninefold coordinated and diphosphate groups adopt a staggered (alternated) configuration. In the case of triclinic ErHP 2 O 7 ·3H 2 O (type II), erbium cations are eightfold coordinated and diphosphate groups adopt an eclipsed configuration. In agreement with Infrared (IR) spectroscopic data, a bended configuration for diphosphate groups has been deduced. In both structures, one-dimensional chains of edge-sharing rare-earth polyhedra are linked together by diphosphate groups to form the phosphate layers. In both diphosphates, PO 4 and HPO 4 environments have been identified by 31 P MAS-NMR technique. In the two compounds, OH groups of HPO 4 tetrahedra point out of diphosphate planes interacting with adjacent layers. In La-diphosphate, the interaction between HPO 4 groups and water molecules of adjacent layers is favored; however, in Er-diphosphate, the interaction between phosphate acid groups of contiguous layers is produced. Based on structural information deduced, differences detected in IR and NMR spectra of two disphosphates are discussed

  2. Divergent mechanisms underlie Smad4-mediated positive regulation of the three genes encoding the basement membrane component laminin-332 (laminin-5)

    International Nuclear Information System (INIS)

    Zboralski, Dirk; Böckmann, Miriam; Zapatka, Marc; Hoppe, Sabine; Schöneck, Anna; Hahn, Stephan A; Schmiegel, Wolff; Schwarte-Waldhoff, Irmgard

    2008-01-01

    Functional inactivation of the tumor suppressor Smad4 in colorectal and pancreatic carcinogenesis occurs coincident with the transition to invasive growth. Breaking the basement membrane (BM) barrier, a prerequisite for invasive growth, can be due to tumor induced proteolytic tissue remodeling or to reduced synthesis of BM molecules by incipient tumor cells. Laminin-332 (laminin-5), a heterotrimeric BM component composed of α3-, β3- and γ2-chains, has recently been identified as a target structure of Smad4 and represents the first example for expression control of an essential BM component by a tumor and invasion suppressor. Biochemically Smad4 is a transmitter of signals of the TGFβ superfamily of cytokines. We have reported previously, that Smad4 functions as a positive transcriptional regulator of constitutive and of TGFβ-induced transcription of all three genes encoding Laminin-332, LAMA3, LAMB3 and LAMC2. Promoter-reporter constructs harboring 4 kb upstream regions, each of the three genes encoding Laminin-322 as well as deletion and mutations constructs were established. Promoter activities and TGFβ induction were assayed through transient transfections in Smad4-negative human cancer cells and their stable Smad4-positive derivatives. Functionally relevant binding sites were subsequently confirmed through chromatin immunoprecipitation. Herein, we report that Smad4 mediates transcriptional regulation through three different mechanisms, namely through Smad4 binding to a functional SBE site exclusively in the LAMA3 promoter, Smad4 binding to AP1 (and Sp1) sites presumably via interaction with AP1 family components and lastly a Smad4 impact on transcription of AP1 factors. Whereas Smad4 is essential for positive regulation of all three genes, the molecular mechanisms are significantly divergent between the LAMA3 promoter as compared to the LAMB3 and LAMC2 promoters. We hypothesize that this divergence in modular regulation of the three promoters may lay the

  3. Aurora-A regulates MCRS1 function during mitosis.

    Science.gov (United States)

    Meunier, Sylvain; Timón, Krystal; Vernos, Isabelle

    2016-07-02

    The mitotic spindle is made of microtubules (MTs) nucleated through different pathways involving the centrosomes, the chromosomes or the walls of pre-existing MTs. MCRS1 is a RanGTP target that specifically associates with the chromosome-driven MTs protecting them from MT depolymerases. MCRS1 is also needed for the control of kinetochore fiber (K-fiber) MT minus-ends dynamics in metaphase. Here, we investigated the regulation of MCRS1 activity in M-phase. We show that MCRS1 is phosphorylated by the Aurora-A kinase in mitosis on Ser35/36. Although this phosphorylation has no role on MCRS1 localization to chromosomal MTs and K-fiber minus-ends, we show that it regulates MCRS1 activity in mitosis. We conclude that Aurora-A activity is particularly important in the tuning of K-fiber minus-ends dynamics in mitosis.

  4. A setup for measurement of beam stability and position using position sensitive detector for Indus-1

    International Nuclear Information System (INIS)

    Nathwani, R.K.; Joshi, D.K.; Tyagi, Y.; Soni, R.S.; Puntambekar, T.A.; Pithawa, C.K.

    2009-01-01

    The 450 MeV electron synchrotron radiation source Indus-1 is operational at RRCAT. A set-up has been developed to measure the relative transverse positional stability of the electron beam and its position with microns resolution using position sensitive photodiodes. The set-up has been installed at the diagnostics beam line of Indus-1. Synchrotron light from photo physics beamline was reflected out by inserting a Ni coated mirror and was focused onto a duo-lateral position sensitive photodiode by using two mirrors of 1.25 meter focal length to obtain unity magnification. The set-up consists of a duo-lateral position sensitive detector (PSD), precision processing electronics and a PC based data acquisition system. A computer program captures the processed signals on to a PC using GPIB interface and displays vertical position of the beam in real time. The paper describes the salient features of the setup developed for measurement of beam stability. (author)

  5. The E2F-DP1 Transcription Factor Complex Regulates Centriole Duplication in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Jacqueline G. Miller

    2016-03-01

    Full Text Available Centrioles play critical roles in the organization of microtubule-based structures, from the mitotic spindle to cilia and flagella. In order to properly execute their various functions, centrioles are subjected to stringent copy number control. Central to this control mechanism is a precise duplication event that takes place during S phase of the cell cycle and involves the assembly of a single daughter centriole in association with each mother centriole . Recent studies have revealed that posttranslational control of the master regulator Plk4/ZYG-1 kinase and its downstream effector SAS-6 is key to ensuring production of a single daughter centriole. In contrast, relatively little is known about how centriole duplication is regulated at a transcriptional level. Here we show that the transcription factor complex EFL-1-DPL-1 both positively and negatively controls centriole duplication in the Caenorhabditis elegans embryo. Specifically, we find that down regulation of EFL-1-DPL-1 can restore centriole duplication in a zyg-1 hypomorphic mutant and that suppression of the zyg-1 mutant phenotype is accompanied by an increase in SAS-6 protein levels. Further, we find evidence that EFL-1-DPL-1 promotes the transcription of zyg-1 and other centriole duplication genes. Our results provide evidence that in a single tissue type, EFL-1-DPL-1 sets the balance between positive and negative regulators of centriole assembly and thus may be part of a homeostatic mechanism that governs centriole assembly.

  6. Meis1 regulates Foxn4 expression during retinal progenitor cell differentiation

    Directory of Open Access Journals (Sweden)

    Mohammed M. Islam

    2013-09-01

    The transcription factor forkhead box N4 (Foxn4 is a key regulator in a variety of biological processes during development. In particular, Foxn4 plays an essential role in the genesis of horizontal and amacrine neurons from neural progenitors in the vertebrate retina. Although the functions of Foxn4 have been well established, the transcriptional regulation of Foxn4 expression during progenitor cell differentiation remains unclear. Here, we report that an evolutionarily conserved 129 bp noncoding DNA fragment (Foxn4CR4.2 or CR4.2, located ∼26 kb upstream of Foxn4 transcription start site, functions as a cis-element for Foxn4 regulation. CR4.2 directs gene expression in Foxn4-positive cells, primarily in progenitors, differentiating horizontal and amacrine cells. We further determined that the gene regulatory activity of CR4.2 is modulated by Meis1 binding motif, which is bound and activated by Meis1 transcription factor. Deletion of the Meis1 binding motif or knockdown of Meis1 expression abolishes the gene regulatory activity of CR4.2. In addition, knockdown of Meis1 expression diminishes the endogenous Foxn4 expression and affects cell lineage development. Together, we demonstrate that CR4.2 and its interacting Meis1 transcription factor play important roles in regulating Foxn4 expression during early retinogenesis. These findings provide new insights into molecular mechanisms that govern gene regulation in retinal progenitors and specific cell lineage development.

  7. N-Myc Differentially Regulates Expression of MXI1 Isoforms in Neuroblastoma

    Directory of Open Access Journals (Sweden)

    Michael B. Armstrong

    2013-12-01

    Full Text Available Amplification of the MYCN proto-oncogene is associated with a poor prognosis in patients with metastatic neuroblastoma (NB. MYCN encodes the N-Myc protein, a transcriptional regulator that dimerizes with the Max transcription factor, binds to E-box DNA sequences, and regulates genes involved in cell growth and apoptosis. Overexpression of N-Myc leads to transcriptional activation and an increase in NB cell proliferation. Mxi1, a member of the Myc family of transcriptional regulators, also binds to Max. However, Mxi1 is a transcriptional repressor and inhibits proliferation of NB cells, suggesting that Mxi1 functions as an N-Myc antagonist. Our laboratory previously identified Mxi1-0, an alternatively transcribed Mxi1 isoform. Mxi1-0 has properties distinct from those of Mxi1; in contrast to Mxi1, Mxi1-0 is unable to suppress c-Myc-dependent transcription. We now show that Mxi1-0 expression increases in response to MYCN overexpression in NB cells, with a positive correlation between MYCN and MXI1-0 RNA levels. We also show that N-Myc expression differentially regulates the MXI1 and MXI1-0 promoters: Increased MYCN expression suppresses MXI1 promoter activity while enhancing transcription through the MXI1-0 promoter. Finally, induction of Mxi1-0 leads to increased proliferation, whereas expression of Mxi1 inhibits cell growth, indicating differential roles for these two proteins. These data suggest that N-Myc differentially regulates the expression of MXI1 and MXI1-0 and can alter the balance between the two transcription factors. Furthermore, MXI1-0 appears to be a downstream target of MYCN-dependent signaling pathways and may contribute to N-Myc-dependent cell growth and proliferation.

  8. Identification of YB-1 as a regulator of PTP1B expression: implications for regulation of insulin and cytokine signaling

    Science.gov (United States)

    Fukada, Toshiyuki; Tonks, Nicholas K.

    2003-01-01

    Changes in expression of PTP1B, the prototypic protein tyrosine phosphatase, have been associated with various human diseases; however, the mechanisms by which PTP1B expression is regulated have not been defined. We have identified an enhancer sequence within the PTP1B promoter which serves as a binding site for the transcription factor Y box-binding protein-1 (YB-1). Overexpression of YB-1 resulted in increased levels of PTP1B. Furthermore, depletion of YB-1 protein, by expression of a specific antisense construct, led to an ∼70% decrease in expression of PTP1B, but no change in the level of its closest relative, TC-PTP. Expression of antisense YB-1 resulted in increased sensitivity to insulin and enhanced signaling through the cytokine receptor gp130, which was suppressed by re-expression of PTP1B. Finally, we observed a correlation between the expression of PTP1B and that of YB-1 in cancer cell lines and an animal model of type II diabetes. Our data reveal an important role for YB-1 as a regulator of PTP1B expression, and further highlight PTP1B as a critical regulator of insulin- and cytokine-mediated signal transduction. PMID:12554649

  9. CESEC III code conversion from Apollo to HP9000

    International Nuclear Information System (INIS)

    Lee, Hae Cho

    1996-01-01

    CESEC code is a computer program used to analyze transient behaviour of reactor coolant systems of nuclear power plants. CESEC III is an extension of original CESEC code in order to apply wide range of accident analysis including ATWS model. Major parameters during the transients are calculated by CESEC. This report firstly describes detailed work carried out for installation of CESEC III on Apollo DN10000 and code validation results after installation. Secondly, A series of work is also described in relation to installation of CESECIII on HP 9000/700 series as well as relevant code validation results. Attached is a report on software verification and validation results. 7 refs. (Author) .new

  10. CESEC III code conversion from Apollo to HP9000

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hae Cho [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1996-01-01

    CESEC code is a computer program used to analyze transient behaviour of reactor coolant systems of nuclear power plants. CESEC III is an extension of original CESEC code in order to apply wide range of accident analysis including ATWS model. Major parameters during the transients are calculated by CESEC. This report firstly describes detailed work carried out for installation of CESEC III on Apollo DN10000 and code validation results after installation. Secondly, A series of work is also described in relation to installation of CESECIII on HP 9000/700 series as well as relevant code validation results. Attached is a report on software verification and validation results. 7 refs. (Author) .new.

  11. Tumor Suppressor RARRES1 Regulates DLG2, PP2A, VCP, EB1, and Ankrd26

    Directory of Open Access Journals (Sweden)

    Ziad J. Sahab, Michael D. Hall, Lihua Zhang, Amrita K. Cheema, Stephen W. Byers

    2010-01-01

    Full Text Available Retinoic Acid Receptor Responder (RARRES1 initially identified as a novel retinoic acid receptor regulated gene in the skin is a putative tumor suppressor of unknown function. RARRES1 was knocked down in immortalized human prostatic epithelial cell line PWR-1E cells and differential protein expression was identified using differential in-gel electrophoresis (DIGE followed by matrix-assisted laser desorption ionization (MALDI mass spectrometry and western Blot analysis excluding highly abundant proteins routinely identified in almost all proteomics projects. Knock-down of RARRES1: 1- down-regulates PP2A, an enzyme involved in the negative regulation of the growth hormone-stimulated signal transduction pathways; 2- down-regulates Valosin-containing protein causing impaired autophagy; 3- up-regulates the tumor suppressor disks large 2; 4- up-regulates Ankrd26 that belongs to the POTE family of genes that are highly expressed in cancer patients with poor outcome; and 5- down-regulates EB1, a protein that is involved in spindle dynamics and chromosome alignment during mitosis.

  12. 1 nA beam position monitoring system

    International Nuclear Information System (INIS)

    Ursic, R.; Flood, R.; Piller, C.

    1997-01-01

    A system has been developed at Jefferson Lab for measuring transverse position of very low current beams delivered to the Experimental Hall B of the Continuous Electron Beam Accelerator Facility (CEBAF). At the heart of the system is a position sensitive cavity operating at 1497 MHz. The cavity utilizes a unique design which achieves a high sensitivity to beam position at a relatively low cavity Q. The cavity output RF signal is processed using a down-converter and a commercial lock-in amplifier operating at 100 kHz. The system interfaces with a VME based EPICS control system using the IEEE, 488 bus. The main features of the system are simple and robust design, and wide dynamic range capable of handling beam currents from 1 nA to 1000 nA with an expected resolution better than 100 μm. This paper outlines the design of the system

  13. Hepatitis B virus surface antigen (HBsAg)-positive and HBsAg-negative hepatitis B virus infection among mother-teenager pairs 13 years after neonatal hepatitis B virus vaccination.

    Science.gov (United States)

    Yao, Qing-Qing; Dong, Xiao-Lian; Wang, Xue-Cai; Ge, Sheng-Xiang; Hu, An-Qun; Liu, Hai-Yan; Wang, Yueping Alex; Yuan, Quan; Zheng, Ying-Jie

    2013-02-01

    It is unclear whether a mother who is negative for hepatitis B virus surface antigen (HBsAg) but positive for hepatitis B virus (HBV) is at potential risk for mother-to-child transmission of HBV. This study, using a paired mother-teenager population, aimed to assess whether maternal HBsAg-negative HBV infection ((hn)HBI) is a significant source of child HBV infection (HBI). A follow-up study with blood collection has been conducted on the 93 mother-teenager pairs from the initial 135 pregnant woman-newborn pairs 13 years after neonatal HBV vaccination. Serological and viral markers of HBV have been tested, and phylogenetic analysis of HBV isolates has been done. The HBI prevalence was 1.9% (1 (hn)HBI/53) for teenage children of non-HBI mothers, compared with 16.7% (1 (hn)HBI/6) for those of (hn)HBI mothers and 2.9% (1 HBsAg-positive HBV infection [(hp)HBI]/34) for those of (hp)HBI mothers. Similar viral sequences have been found in one pair of whom both the mother and teenager have had (hn)HBI. In comparison with the (hp)HBI cases, those with (hn)HBI had a lower level of HBV load and a higher proportion of genotype-C strains, which were accompanied by differentiated mutations (Q129R, K141E, and Y161N) of the "a" determinant of the HBV surface gene. Our findings suggest that mother-to-teenager transmission of (hn)HBI can occur among those in the neonatal HBV vaccination program.

  14. Increased visfatin levels are associated with higher disease activity in anti-Jo-1-positive myositis patients.

    Science.gov (United States)

    Hulejová, Hana; Kryštůfková, Olga; Mann, Heřman; Klein, Martin; Pavlíčková, Klára; Zámečník, Josef; Vencovský, Jiří; Šenolt, Ladislav

    2016-01-01

    The aim of this study was to evaluate serum levels of visfatin in anti-Jo-1-positive myositis patients, its expression in muscle tissue and to investigate potential relationships between visfatin, B-cell activating factor of the TNF family (BAFF), disease activity and anti-Jo-1 autoantibody levels. Serum levels of visfatin and BAFF were measured in 38 anti-Jo-1 positive myositis patients and 35 healthy subjects. Disease activity was evaluated by myositis disease activity assessment tool (MYOACT) using visual analogue scales (VAS) and by serum muscle enzymes. Visfatin expression was evaluated by immunohistochemistry in muscle tissue of myositis patients (n=10) and compared with non-inflammatory control muscle tissue samples from patients with myasthenia gravis (n=5). Serum visfatin and BAFF levels were significantly higher in myositis patients compared to healthy subjects and were associated with clinical muscle activity assessed by VAS. Only serum BAFF levels, but not visfatin levels, positively correlated with muscle enzyme concentrations and anti-Jo1 antibody levels. There was a positive correlation between visfatin and BAFF serum levels in myositis patients but a negative correlation was observed in healthy subjects. Visfatin expression was up-regulated in endomysial and perimysial inflammatory infiltrates of muscle tissue from myositis patients. Up-regulation of visfatin in myositis muscle tissue and an association between increased visfatin levels and muscle disease activity evaluated by MYOACT in anti-Jo-1 positive myositis patients could support possible role of visfatin in the pathogenesis of myositis.

  15. Hydrostatic pressure acts to stabilise a chondrogenic phenotype in porcine joint tissue derived stem cells

    Directory of Open Access Journals (Sweden)

    T Vinardell

    2012-02-01

    Full Text Available Hydrostatic pressure (HP is a key component of the in vivo joint environment and has been shown to enhance chondrogenesis of stem cells. The objective of this study was to investigate the interaction between HP and TGF-β3 on both the initiation and maintenance of a chondrogenic phenotype for joint tissue derived stem cells. Pellets generated from porcine chondrocytes (CCs, synovial membrane derived stem cells (SDSCs and infrapatellar fat pad derived stem cells (FPSCs were subjected to 10 MPa of cyclic HP (4 h/day and different concentrations of TGF-β3 (0, 1 and 10 ng/mL for 14 days. CCs and stem cells were observed to respond differentially to both HP and TGF-β3 stimulation. HP in the absence of TGF-β3 did not induce robust chondrogenic differentiation of stem cells. At low concentrations of TGF-β3 (1 ng/mL, HP acted to enhance chondrogenesis of both SDSCs and FPSCs, as evident by a 3-fold increase in Sox9 expression and a significant increase in glycosaminoglycan accumulation. In contrast, HP had no effect on cartilage-specific matrix synthesis at higher concentrations of TGF-β3 (10 ng/mL. Critically, HP appears to play a key role in the maintenance of a chondrogenic phenotype, as evident by a down-regulation of the hypertrophic markers type X collagen and Indian hedgehog in SDSCs irrespective of the cytokine concentration. In the context of stem cell based therapies for cartilage repair, this study demonstrates the importance of considering how joint specific environmental factors interact to regulate not only the initiation of chondrogenesis, but also the development of a stable hyaline-like repair tissue.

  16. Basal transcription of APOBEC3G is regulated by USF1 gene in hepatocyte

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Yanli [Department of Infectious Diseases, Zhengzhou University People' s Hospital (Henan Provincial People' s Hospital), Zhengzhou, 450003 (China); Li, Hui [The Central Hospital of Wuhan, Tongji Medical College Huazhong University of Science Technology, Wuhan, 430000 (China); Zhang, Xiaoju [Department of Respiratory Medicine, Zhengzhou University People' s Hospital (Henan Provincial People' s Hospital), Zhengzhou, 450003 (China); Shang, Jia [Department of Infectious Diseases, Zhengzhou University People' s Hospital (Henan Provincial People' s Hospital), Zhengzhou, 450003 (China); Kang, Yi, E-mail: kykangyi@163.com [Department of Infectious Diseases, Zhengzhou University People' s Hospital (Henan Provincial People' s Hospital), Zhengzhou, 450003 (China)

    2016-01-29

    Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G, A3G) exert antiviral defense as an important factor of innate immunity. A variety of cytokines such as IFN-γ,IL2,IL15,IL7 could induce the transcription of A3G. However, the regulation of other nuclear factor on the transcription of A3G have not been reported at the present. To gain new insights into the transcriptional regulation of this restriction factor, we cloned and characterized the promoter region of A3G and investigate the modulation of USF1 gene on the transcription of A3G. We identified a 232 bp region that was sufficient to regulate the activity of full promoter. Transcriptional start sites (TSS) were identified by the luciferase reporter assays of plasmids containing full or shorter fragments of the A3G promoter. The results demonstrated that the core promoter of A3G is located within the region -159/-84 relative to the TSS. Transcriptional activity of A3G core promoter regulated by USF1 was dependent on an E-box (located at position -91/-86 relative to the major TSS) and was abolished after mutation of this DNA element. USF1 gene can take part in basal transcription regulation of the human A3G gene in hepatocyte, and the identified E-box represented a binding site for the USF1. - Highlights: • The core promoter of A3G is located within the region −159/−84 relative to the TSS. • Transcriptional activity of A3G core promoter regulated by USF1 was dependent on an E-box (located at position −91/−86 relative to the major TSS). • USF1 gene can take part in basal transcription regulation of the human A3G gene in hepatocyte.

  17. Basal transcription of APOBEC3G is regulated by USF1 gene in hepatocyte

    International Nuclear Information System (INIS)

    Zeng, Yanli; Li, Hui; Zhang, Xiaoju; Shang, Jia; Kang, Yi

    2016-01-01

    Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G, A3G) exert antiviral defense as an important factor of innate immunity. A variety of cytokines such as IFN-γ,IL2,IL15,IL7 could induce the transcription of A3G. However, the regulation of other nuclear factor on the transcription of A3G have not been reported at the present. To gain new insights into the transcriptional regulation of this restriction factor, we cloned and characterized the promoter region of A3G and investigate the modulation of USF1 gene on the transcription of A3G. We identified a 232 bp region that was sufficient to regulate the activity of full promoter. Transcriptional start sites (TSS) were identified by the luciferase reporter assays of plasmids containing full or shorter fragments of the A3G promoter. The results demonstrated that the core promoter of A3G is located within the region -159/-84 relative to the TSS. Transcriptional activity of A3G core promoter regulated by USF1 was dependent on an E-box (located at position -91/-86 relative to the major TSS) and was abolished after mutation of this DNA element. USF1 gene can take part in basal transcription regulation of the human A3G gene in hepatocyte, and the identified E-box represented a binding site for the USF1. - Highlights: • The core promoter of A3G is located within the region −159/−84 relative to the TSS. • Transcriptional activity of A3G core promoter regulated by USF1 was dependent on an E-box (located at position −91/−86 relative to the major TSS). • USF1 gene can take part in basal transcription regulation of the human A3G gene in hepatocyte.

  18. Tyrosine Phosphorylation of Rac1: A Role in Regulation of Cell Spreading

    Science.gov (United States)

    Chang, Fumin; Lemmon, Christopher; Lietha, Daniel; Eck, Michael; Romer, Lewis

    2011-01-01

    Rac1 influences a multiplicity of vital cellular- and tissue-level control functions, making it an important candidate for targeted therapeutics. The activity of the Rho family member Cdc42 has been shown to be modulated by tyrosine phosphorylation at position 64. We therefore investigated consequences of the point mutations Y64F and Y64D in Rac1. Both mutations altered cell spreading from baseline in the settings of wild type, constitutively active, or dominant negative Rac1 expression, and were accompanied by differences in Rac1 targeting to focal adhesions. Rac1-Y64F displayed increased GTP-binding, increased association with βPIX, and reduced binding with RhoGDI as compared with wild type Rac1. Rac1-Y64D had less binding to PAK than Rac1-WT or Rac1-64F. In vitro assays demonstrated that Y64 in Rac1 is a target for FAK and Src. Taken together, these data suggest a mechanism for the regulation of Rac1 activity by non-receptor tyrosine kinases, with consequences for membrane extension. PMID:22163037

  19. Munc13-4 Is a Rab11-binding Protein That Regulates Rab11-positive Vesicle Trafficking and Docking at the Plasma Membrane.

    Science.gov (United States)

    Johnson, Jennifer L; He, Jing; Ramadass, Mahalakshmi; Pestonjamasp, Kersi; Kiosses, William B; Zhang, Jinzhong; Catz, Sergio D

    2016-02-12

    The small GTPase Rab11 and its effectors control trafficking of recycling endosomes, receptor replenishment and the up-regulation of adhesion and adaptor molecules at the plasma membrane. Despite recent advances in the understanding of Rab11-regulated mechanisms, the final steps mediating docking and fusion of Rab11-positive vesicles at the plasma membrane are not fully understood. Munc13-4 is a docking factor proposed to regulate fusion through interactions with SNAREs. In hematopoietic cells, including neutrophils, Munc13-4 regulates exocytosis in a Rab27a-dependent manner, but its possible regulation of other GTPases has not been explored in detail. Here, we show that Munc13-4 binds to Rab11 and regulates the trafficking of Rab11-containing vesicles. Using a novel Time-resolved Fluorescence Resonance Energy Transfer (TR-FRET) assay, we demonstrate that Munc13-4 binds to Rab11a but not to dominant negative Rab11a. Immunoprecipitation analysis confirmed the specificity of the interaction between Munc13-4 and Rab11, and super-resolution microscopy studies support the interaction of endogenous Munc13-4 with Rab11 at the single molecule level in neutrophils. Vesicular dynamic analysis shows the common spatio-temporal distribution of Munc13-4 and Rab11, while expression of a calcium binding-deficient mutant of Munc13-4 significantly affected Rab11 trafficking. Munc13-4-deficient neutrophils showed normal endocytosis, but the trafficking, up-regulation, and retention of Rab11-positive vesicles at the plasma membrane was significantly impaired. This correlated with deficient NADPH oxidase activation at the plasma membrane in response to Rab11 interference. Our data demonstrate that Munc13-4 is a Rab11-binding partner that regulates the final steps of Rab11-positive vesicle docking at the plasma membrane. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Developing Consensus on the CompHP Professional Standards for Health Promotion in Europe

    Science.gov (United States)

    Speller, Viv; Parish, Richard; Davison, Heather; Zilnyk, Anna

    2012-01-01

    Building on the CompHP Core Competencies for health promotion the Professional Standards for Health Promotion have been developed and consulted on across Europe. The standards were formulated to fit within the complexity of professional, occupational and educational standards frameworks in Europe as learning outcome standards with performance…

  1. HP Memristor mathematical model for periodic signals and DC

    KAUST Repository

    Radwan, Ahmed G.

    2012-07-28

    In this paper mathematical models of the HP Memristor for DC and periodic signal inputs are provided. The need for a rigid model for the Memristor using conventional current and voltage quantities is essential for the development of many promising Memristors\\' applications. Unlike the previous works, which focuses on the sinusoidal input waveform, we derived rules for any periodic signals in general in terms of voltage and current. Square and triangle waveforms are studied explicitly, extending the formulas for any general square wave. The limiting conditions for saturation are also provided in case of either DC or periodic signals. The derived equations are compared to the SPICE model of the Memristor showing a perfect match.

  2. CCN4/WISP-1 positively regulates chondrogenesis by controlling TGF-β3 function.

    Science.gov (United States)

    Yoshioka, Yuya; Ono, Mitsuaki; Maeda, Azusa; Kilts, Tina M; Hara, Emilio Satoshi; Khattab, Hany; Ueda, Junji; Aoyama, Eriko; Oohashi, Toshitaka; Takigawa, Masaharu; Young, Marian F; Kuboki, Takuo

    2016-02-01

    The CCN family of proteins plays important roles in development and homeostasis of bone and cartilage. To understand the role of CCN4 in chondrogenesis, human bone marrow stromal cells (hBMSCs) were transduced with CCN4 adenovirus (adCCN4) or siRNA to CCN4 (siCCN4) in the presence or absence of transforming growth factor-β3 (TGF-β3). Overexpression of CCN4 enhanced TGF-β3-induced SMAD2/3 phosphorylation and chondrogenesis of hBMSCs in an in vitro assay using a micromass culture model. On the other hand, knockdown of CCN4 inhibited the TGF-β3-induced SMAD2/3 phosphorylation and synthesis of cartilage matrix in micromass cultures of hBMSCs. Immunoprecipitation-western blot analysis revealed that CCN4 bound to TGF-β3 and regulated the ability of TGF-β3 to bind to hBMSCs. In vivo analysis confirmed there was a significant decrease in the gene expression levels of chondrocyte markers in cartilage samples from Ccn4-knock out (KO) mice, compared to those from wild type (WT) control. In order to investigate the regenerative properties of the articular cartilage in Ccn4-KO mice, articular cartilage defects were surgically performed in the knee joints of young mice, and the results showed that the cartilage was partially repaired in WT mice, but not in Ccn4-KO mice. In conclusion, these results show, for the first time, that CCN4 has a positive influence on chondrogenic differentiation by modulating the effects of TGF-β3. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Rac1 GTPase regulates 11β hydroxysteroid dehydrogenase type 2 and fibrotic remodeling.

    Science.gov (United States)

    Lavall, Daniel; Schuster, Pia; Jacobs, Nadine; Kazakov, Andrey; Böhm, Michael; Laufs, Ulrich

    2017-05-05

    The aim of the study was to characterize the role of Rac1 GTPase for the mineralocorticoid receptor (MR)-mediated pro-fibrotic remodeling. Transgenic mice with cardiac overexpression of constitutively active Rac1 (RacET) develop an age-dependent phenotype with atrial dilatation, fibrosis, and atrial fibrillation. Expression of MR was similar in RacET and WT mice. The expression of 11β hydroxysteroid dehydrogenase type 2 (11β-HSD2) was age-dependently up-regulated in the atria and the left ventricles of RacET mice on mRNA and protein levels. Statin treatment inhibiting Rac1 geranylgeranylation reduced 11β-HSD2 up-regulation. Samples of human left atrial myocardium showed a positive correlation between Rac1 activity and 11β-HSD2 expression ( r = 0.7169). Immunoprecipitation showed enhanced Rac1-bound 11β-HSD2 relative to Rac1 expression in RacET mice that was diminished with statin treatment. Both basal and phorbol 12-myristate 13-acetate (PMA)-induced NADPH oxidase activity were increased in RacET and correlated positively with 11β-HSD2 expression ( r = 0.788 and r = 0.843, respectively). In cultured H9c2 cardiomyocytes, Rac1 activation with l-buthionine sulfoximine increased; Rac1 inhibition with NSC23766 decreased 11β-HSD2 mRNA and protein expression. Connective tissue growth factor (CTGF) up-regulation induced by aldosterone was prevented with NSC23766. Cardiomyocyte transfection with 11β-HSD2 siRNA abolished the aldosterone-induced CTGF up-regulation. Aldosterone-stimulated MR nuclear translocation was blocked by the 11β-HSD2 inhibitor carbenoxolone. In cardiac fibroblasts, nuclear MR translocation induced by aldosterone was inhibited with NSC23766 and spironolactone. NSC23766 prevented the aldosterone-induced proliferation and migration of cardiac fibroblasts and the up-regulation of CTGF and fibronectin. In conclusion, Rac1 GTPase regulates 11β-HSD2 expression, MR activation, and MR-mediated pro-fibrotic signaling. © 2017 by The American Society for

  4. FvVE1 Regulates Biosynthesis of Fumonisins and Fusarins in Fusarium verticillioides

    Science.gov (United States)

    MYUNG, KYUNG; LI, SHAOJIE; BUTCHKO, ROBERT A.E.; BUSMAN, MARK; PROCTOR, ROBERT H; ABBAS, HAMED K.; CALVO, ANA M.

    2009-01-01

    The veA gene positively regulates sterigmatocystin production in Aspergillus nidulans and aflatoxin production in A. parasiticus and A. flavus. Whether veA homologs have a role in regulating secondary metabolism in other fungal genera is unknown. In this study, we examined the role of the veA homolog, FvVE1, on production of two mycotoxin families, fumonisins and fusarins, in the important corn pathogen F. verticillioides. We found that FvVE1 deletion completely suppressed fumonisin production on two natural substrates, corn and rice. Furthermore, our results revealed that FvVE1 is necessary for the expression of the pathway-specific regulatory gene FUM21 and structural genes in the fumonisin biosynthetic gene (FUM) cluster. FvVE1 deletion also blocked production of fusarins. The effects of FvVE1 deletion on the production of these toxins were found to be the same in two separate mating types. Our results strongly suggest that FvVE1 play an important role in regulating mycotoxin production in F. verticillioides. PMID:19382792

  5. Cyclin G Functions as a Positive Regulator of Growth and Metabolism in Drosophila.

    Directory of Open Access Journals (Sweden)

    Patrick Fischer

    2015-08-01

    Full Text Available In multicellular organisms, growth and proliferation is adjusted to nutritional conditions by a complex signaling network. The Insulin receptor/target of rapamycin (InR/TOR signaling cascade plays a pivotal role in nutrient dependent growth regulation in Drosophila and mammals alike. Here we identify Cyclin G (CycG as a regulator of growth and metabolism in Drosophila. CycG mutants have a reduced body size and weight and show signs of starvation accompanied by a disturbed fat metabolism. InR/TOR signaling activity is impaired in cycG mutants, combined with a reduced phosphorylation status of the kinase Akt1 and the downstream factors S6-kinase and eukaryotic translation initiation factor 4E binding protein (4E-BP. Moreover, the expression and accumulation of Drosophila insulin like peptides (dILPs is disturbed in cycG mutant brains. Using a reporter assay, we show that the activity of one of the first effectors of InR signaling, Phosphoinositide 3-kinase (PI3K92E, is unaffected in cycG mutants. However, the metabolic defects and weight loss in cycG mutants were rescued by overexpression of Akt1 specifically in the fat body and by mutants in widerborst (wdb, the B'-subunit of the phosphatase PP2A, known to downregulate Akt1 by dephosphorylation. Together, our data suggest that CycG acts at the level of Akt1 to regulate growth and metabolism via PP2A in Drosophila.

  6. Negative-tone imaging with EUV exposure toward 13nm hp

    Science.gov (United States)

    Tsubaki, Hideaki; Nihashi, Wataru; Tsuchihashi, Toru; Yamamoto, Kei; Goto, Takahiro

    2016-03-01

    Negative-tone imaging (NTI) with EUV exposure has major advantages with respect to line-width roughness (LWR) and resolution due in part to polymer swelling and favorable dissolution mechanics. In NTI process, both resist and organic solvents play important roles in determining lithography performances. The present study describes novel chemically amplified resist materials based on NTI technology with EUV using a specific organic solvents. Lithographic performances of NTI process were described in this paper under exposures using ASML NXE:3300 EUV scanner at imec. It is emphasized that 14 nm hp was nicely resolved under exposure dose of 37 mJ/cm2 without any bridge and collapse, which are attributed to the low swelling character of NTI process. Although 13 nm hp resolution was potentially obtained, a pattern collapse still restricts its resolution in case coating resist film thickness is 40 nm. Dark mask limitation due mainly to mask defectivity issue makes NTI with EUV favorable approach for printing block mask to produce logic circuit. A good resolution of CD-X 21 nm/CD-Y 32 nm was obtained for block mask pattern using NTI with usable process window and dose of 49 mJ/cm2. Minimum resolution now reaches CD-X 17 nm / CD-Y 23 nm for the block. A 21 nm block mask resolution was not affected by exposure dose and explored toward low dose down to 18 mJ/cm2 by reducing quencher loading. In addition, there was a negligible amount of increase in LCDU for isolated dot pattern when decreasing exposure dose from 66 mJ/cm2 to 24 mJ/cm2. On the other hand, there appeared tradeoff relationship between LCDU and dose for dense dot pattern, indicating photon-shot noise restriction, but strong dependency on patterning features. Design to improve acid generation efficiency was described based on acid generation mechanism in traditional chemically amplified materials which contains photo-acid generator (PAG) and polymer. Conventional EUV absorber comprises of organic compounds is

  7. Classification of atrophic mucosal patterns on Blue LASER Imaging for endoscopic diagnosis of Helicobacter pylori-related gastritis: A retrospective, observational study.

    Science.gov (United States)

    Nishikawa, Yoshiyuki; Ikeda, Yoshio; Murakami, Hidehiro; Hori, Shin-Ichiro; Hino, Kaori; Sasaki, Chise; Nishikawa, Megumi

    2018-01-01

    Atrophic gastritis can be classified according to characteristic mucosal patterns observed by Blue LASER Imaging (BLI) in a medium-range to distant view. To facilitate the endoscopic diagnosis of Helicobacter pylori (HP)-related gastritis, we investigated whether atrophic mucosal patterns correlated with HP infection based on the image interpretations of three endoscopists blinded to clinical features. This study included 441 patients diagnosed as having atrophic gastritis by upper gastrointestinal endoscopy at Nishikawa Gastrointestinal Clinic between April 1, 2015 and March 31, 2016. The presence/absence of HP infection was not taken into consideration. Endoscopy was performed using a Fujifilm EG-L580NW scope. Atrophic mucosal patterns observed by BLI were classified into Spotty, Cracked and Mottled. Image interpretation results were that 89, 122 and 228 patients had the Spotty, Cracked and Mottled patterns, respectively, and 2 patients an undetermined pattern. Further analyses were performed on 439 patients, excluding the 2 with undetermined patterns. The numbers of patients testing negative/positive for HP infection in the Spotty, Cracked and Mottled pattern groups were 12/77, 105/17, and 138/90, respectively. The specificity, positive predictive value and positive likelihood ratio for endoscopic diagnosis with positive HP infection based on the Spotty pattern were 95.3%, 86.5% and 8.9, respectively. In all patients with the Spotty pattern before HP eradication, the Cracked pattern was observed on subsequent post-eradication endoscopy. The Spotty pattern may represent the presence of HP infection, the Cracked pattern, a post-inflammatory change as seen after HP eradication, and the Mottled pattern, intestinal metaplasia.

  8. Lasp-1 regulates podosome function.

    Directory of Open Access Journals (Sweden)

    Miriam Stölting

    Full Text Available Eukaryotic cells form a variety of adhesive structures to connect with their environment and to regulate cell motility. In contrast to classical focal adhesions, podosomes, highly dynamic structures of different cell types, are actively engaged in matrix remodelling and degradation. Podosomes are composed of an actin-rich core region surrounded by a ring-like structure containing signalling molecules, motor proteins as well as cytoskeleton-associated proteins. Lasp-1 is a ubiquitously expressed, actin-binding protein that is known to regulate cytoskeleton architecture and cell migration. This multidomain protein is predominantely present at focal adhesions, however, a second pool of Lasp-1 molecules is also found at lamellipodia and vesicle-like microdomains in the cytosol.In this report, we show that Lasp-1 is a novel component and regulator of podosomes. Immunofluorescence studies reveal a localization of Lasp-1 in the podosome ring structure, where it colocalizes with zyxin and vinculin. Life cell imaging experiments demonstrate that Lasp-1 is recruited in early steps of podosome assembly. A siRNA-mediated Lasp-1 knockdown in human macrophages affects podosome dynamics as well as their matrix degradation capacity. In summary, our data indicate that Lasp-1 is a novel component of podosomes and is involved in the regulation of podosomal function.

  9. Conversion of the COBRA-IV-I code from CDC CYBER to HP 9000/700 version

    International Nuclear Information System (INIS)

    Sohn, D. S.; Yoo, Y. J.; Nahm, K. Y.; Hwang, D. H.

    1996-01-01

    COBRA-IV-I is a multichannel analysis code for the thermal-hydraulic analysis of rod bundle nuclear fuel elements and cores based on the subchannel approach. The existing COBRA-IV-I code is the control data corporation (CDC) CYBER version, which has limitations on the computer core storage and gives some inconvenience to the user interface. To solve these problems, we have converted the COBRA-IV-I code form the CDC CYBER mainframe to an Hewlett Packard (HP) 9000/700-series workstation version, and have verified the converted code. as a result, we have found almost no difference between the two versions in their calculation results. Therefore we expect the HP 9000/700 version of the COBRA-IV-I code to be the basis for the future development of an improved multichannel analysis code under the more convenient user environment. (author). 3 tabs., 2 figs., 8 refs

  10. Application of the EC eco-audit regulation in the energy industry

    International Nuclear Information System (INIS)

    Schulz, J.

    1994-01-01

    The eco-audit regulation isolates the precision of goals to improve operational environmental protection for observation, particularly with a view to the industrial energy economy. It is not wise without an investigation into the possible repercussions with other EU and national regulatory laws. Keywords here are: design of a heat application regulation according to the BImSchG, discussion over the introduction of an EC CO 2 Energy tax as well as the EC guidelines on reducing CO 2 emissions (SAVE). (orig./HP) [de

  11. Ancient and recent positive selection transformed opioid cis-regulation in humans.

    Directory of Open Access Journals (Sweden)

    Matthew V Rockman

    2005-12-01

    Full Text Available Changes in the cis-regulation of neural genes likely contributed to the evolution of our species' unique attributes, but evidence of a role for natural selection has been lacking. We found that positive natural selection altered the cis-regulation of human prodynorphin, the precursor molecule for a suite of endogenous opioids and neuropeptides with critical roles in regulating perception, behavior, and memory. Independent lines of phylogenetic and population genetic evidence support a history of selective sweeps driving the evolution of the human prodynorphin promoter. In experimental assays of chimpanzee-human hybrid promoters, the selected sequence increases transcriptional inducibility. The evidence for a change in the response of the brain's natural opioids to inductive stimuli points to potential human-specific characteristics favored during evolution. In addition, the pattern of linked nucleotide and microsatellite variation among and within modern human populations suggests that recent selection, subsequent to the fixation of the human-specific mutations and the peopling of the globe, has favored different prodynorphin cis-regulatory alleles in different parts of the world.

  12. The Mediator co-activator complex regulates Ty1 retromobility by controlling the balance between Ty1i and Ty1 promoters.

    Science.gov (United States)

    Salinero, Alicia C; Knoll, Elisabeth R; Zhu, Z Iris; Landsman, David; Curcio, M Joan; Morse, Randall H

    2018-02-01

    The Ty1 retrotransposons present in the genome of Saccharomyces cerevisiae belong to the large class of mobile genetic elements that replicate via an RNA intermediary and constitute a significant portion of most eukaryotic genomes. The retromobility of Ty1 is regulated by numerous host factors, including several subunits of the Mediator transcriptional co-activator complex. In spite of its known function in the nucleus, previous studies have implicated Mediator in the regulation of post-translational steps in Ty1 retromobility. To resolve this paradox, we systematically examined the effects of deleting non-essential Mediator subunits on the frequency of Ty1 retromobility and levels of retromobility intermediates. Our findings reveal that loss of distinct Mediator subunits alters Ty1 retromobility positively or negatively over a >10,000-fold range by regulating the ratio of an internal transcript, Ty1i, to the genomic Ty1 transcript. Ty1i RNA encodes a dominant negative inhibitor of Ty1 retromobility that blocks virus-like particle maturation and cDNA synthesis. These results resolve the conundrum of Mediator exerting sweeping control of Ty1 retromobility with only minor effects on the levels of Ty1 genomic RNA and the capsid protein, Gag. Since the majority of characterized intrinsic and extrinsic regulators of Ty1 retromobility do not appear to effect genomic Ty1 RNA levels, Mediator could play a central role in integrating signals that influence Ty1i expression to modulate retromobility.

  13. The Mechanisms of Virulence Regulation by Small Noncoding RNAs in Low GC Gram-Positive Pathogens

    Directory of Open Access Journals (Sweden)

    Stephanie Pitman

    2015-12-01

    Full Text Available The discovery of small noncoding regulatory RNAs (sRNAs in bacteria has grown tremendously recently, giving new insights into gene regulation. The implementation of computational analysis and RNA sequencing has provided new tools to discover and analyze potential sRNAs. Small regulatory RNAs that act by base-pairing to target mRNAs have been found to be ubiquitous and are the most abundant class of post-transcriptional regulators in bacteria. The majority of sRNA studies has been limited to E. coli and other gram-negative bacteria. However, examples of sRNAs in gram-positive bacteria are still plentiful although the detailed gene regulation mechanisms behind them are not as well understood. Strict virulence control is critical for a pathogen’s survival and many sRNAs have been found to be involved in that process. This review outlines the targets and currently known mechanisms of trans-acting sRNAs involved in virulence regulation in various gram-positive pathogens. In addition, their shared characteristics such as CU interaction motifs, the role of Hfq, and involvement in two-component regulators, riboswitches, quorum sensing, or toxin/antitoxin systems are described.

  14. GIT1/βPIX signaling proteins and PAK1 kinase regulate microtubule nucleation.

    Science.gov (United States)

    Černohorská, Markéta; Sulimenko, Vadym; Hájková, Zuzana; Sulimenko, Tetyana; Sládková, Vladimíra; Vinopal, Stanislav; Dráberová, Eduarda; Dráber, Pavel

    2016-06-01

    Microtubule nucleation from γ-tubulin complexes, located at the centrosome, is an essential step in the formation of the microtubule cytoskeleton. However, the signaling mechanisms that regulate microtubule nucleation in interphase cells are largely unknown. In this study, we report that γ-tubulin is in complexes containing G protein-coupled receptor kinase-interacting protein 1 (GIT1), p21-activated kinase interacting exchange factor (βPIX), and p21 protein (Cdc42/Rac)-activated kinase 1 (PAK1) in various cell lines. Immunofluorescence microscopy revealed association of GIT1, βPIX and activated PAK1 with centrosomes. Microtubule regrowth experiments showed that depletion of βPIX stimulated microtubule nucleation, while depletion of GIT1 or PAK1 resulted in decreased nucleation in the interphase cells. These data were confirmed for GIT1 and βPIX by phenotypic rescue experiments, and counting of new microtubules emanating from centrosomes during the microtubule regrowth. The importance of PAK1 for microtubule nucleation was corroborated by the inhibition of its kinase activity with IPA-3 inhibitor. GIT1 with PAK1 thus represent positive regulators, and βPIX is a negative regulator of microtubule nucleation from the interphase centrosomes. The regulatory roles of GIT1, βPIX and PAK1 in microtubule nucleation correlated with recruitment of γ-tubulin to the centrosome. Furthermore, in vitro kinase assays showed that GIT1 and βPIX, but not γ-tubulin, serve as substrates for PAK1. Finally, direct interaction of γ-tubulin with the C-terminal domain of βPIX and the N-terminal domain of GIT1, which targets this protein to the centrosome, was determined by pull-down experiments. We propose that GIT1/βPIX signaling proteins with PAK1 kinase represent a novel regulatory mechanism of microtubule nucleation in interphase cells. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Study of the quasi-free scattering at the reaction 2H(p,2p)n at Esub(p)0 = 14.1 MeV

    International Nuclear Information System (INIS)

    Helten, H.J.

    1980-01-01

    The breakup reaction 2 H(p,2p)n was studied at Ep = 14.1 MeV in complete coincidence experiments on quasifree pp scattering in a systematic range of cinematic situations of the pp-subsystem for c.m. production angles between 90 0 and 140 0 and different violation of the quasifree condition as well on interferences with final-state interaction processes. The absolute differential breakup cross section was compared with approximate solutions of the Faddeev equations with separable s-wave potentials without explicite Coulomb interaction according to Ebenhoeh. The agreement is generally good referring to the form of the spectra, but the theoretical amplitude is in the mean 20% to high. The permanent independence of the quasifree breakup from the scattering parameter asub(pp) doesn't suggest to use this process for the determination of nn-scattering lengths from the mirror reaction 2 H(n,2n)p. (orig.)

  16. An h-p Taylor-Galerkin finite element method for compressible Euler equations

    Science.gov (United States)

    Demkowicz, L.; Oden, J. T.; Rachowicz, W.; Hardy, O.

    1991-01-01

    An extension of the familiar Taylor-Galerkin method to arbitrary h-p spatial approximations is proposed. Boundary conditions are analyzed, and a linear stability result for arbitrary meshes is given, showing the unconditional stability for the parameter of implicitness alpha not less than 0.5. The wedge and blunt body problems are solved with both linear, quadratic, and cubic elements and h-adaptivity, showing the feasibility of higher orders of approximation for problems with shocks.

  17. The histone H3K9 methylation and RNAi pathways regulate normalnucleolar and repeated DNA organization by inhibiting formation ofextrachromosomal DNAs

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Jamy C.; Karpen, Gary H.

    2006-06-15

    In order to identify regulators of nuclear organization, Drosophila mutants in the Su(var)3-9 histone H3K9 methyltransferase, RNAi pathway components, and other regulators of heterochromatin-mediated gene silencing were examined for altered nucleoli and positioning of repeated DNAs. Animals lacking components of the H3K9 methylation and RNAi pathways contained disorganized nucleoli, ribosomal DNA (rDNA) and satellite DNAs. The levels of H3K9 dimethylation (H3K9me2) in chromatin associated with repeated DNAs decreased dramatically in Su(var)3-9 and dcr-2 (dicer-2) mutant tissues compared to wild type. We also observed a substantial increase in extrachromosomal repeated DNAs in mutant tissues. The disorganized nucleolus phenotype depends on the presence of Ligase 4 (Lig4), and ecc DNA formation is not induced by removal of cohesin. We conclude that H3K9 methylation of rDNA and satellites, maintained by Su(var)3-9, HP1, and the RNAi pathway, is necessary for the structural stability of repeated DNAs, which is mediated through suppression of non-homologous end joining (NHEJ). These results suggest a mechanism for how local chromatin structure can regulate genome stability, and the organization of chromosomal elements and nuclear organelles.

  18. Perspectives on Industrial Innovation from Agilent, HP, and Bell Labs

    Science.gov (United States)

    Hollenhorst, James

    2014-03-01

    Innovation is the life blood of technology companies. I will give perspectives gleaned from a career in research and development at Bell Labs, HP Labs, and Agilent Labs, from the point of view of an individual contributor and a manager. Physicists bring a unique set of skills to the corporate environment, including a desire to understand the fundamentals, a solid foundation in physical principles, expertise in applied mathematics, and most importantly, an attitude: namely, that hard problems can be solved by breaking them into manageable pieces. In my experience, hiring managers in industry seldom explicitly search for physicists, but they want people with those skills.

  19. UBE2C Is a Transcriptional Target of the Cell Cycle Regulator FOXM1

    Directory of Open Access Journals (Sweden)

    Pedro Nicolau-Neto

    2018-03-01

    Full Text Available FOXM1 (forkhead box protein M1 is a transcription factor that participates in all stages of tumor development, mainly through the control of cell cycle and proliferation, regulating the expression of genes involved in G1/S and G2/M transition and M phase progression. The ubiquitin conjugating enzyme E2 (UBE2C is a member of the anaphase promoting complex/cyclosome, promoting the degradation of several target proteins along cell cycle progression, during metaphase/anaphase transition. FOXM1 and UBE2C have been found overexpressed in a wide range of different solid tumors. Therefore, the aim of this study was to investigate whether UBE2C is a transcriptional target of FOXM1, using esophageal squamous cell carcinoma (ESCC as a model, in addition to several cancer-deposited data. Our results show that FOXM1 and UBE2C expression present a positive correlation in normal tissues and in 25 distinct tumor types, including ESCC, where these genes are overexpressed. Moreover, FOXM1 binds to UBE2C promoter region in ESCC cell line and transcriptionally activates it, leading to UBE2C upregulation. In conclusion, this study provides evidences that FOXM1 transcriptionally regulates UBE2C expression in ESCC and their deregulation may be a general phenomenon in human neoplasias.

  20. Calculation of conversion coefficients Hp(3)/K air using the PENELOPE Monte Carlo code and comparison with MCNP calculation results

    International Nuclear Information System (INIS)

    Daures, J.; Gouriou, J.; Bordy, J.M.

    2010-01-01

    The authors report calculations performed using the MNCP and PENELOPE codes to determine the Hp(3)/K air conversion coefficient which allows the Hp(3) dose equivalent to be determined from the measured value of the kerma in the air. They report the definition of the phantom, a 20 cm diameter and 20 cm high cylinder which is considered as representative of a head. Calculations are performed for an energy range corresponding to interventional radiology or cardiology (20 keV-110 keV). Results obtained with both codes are compared

  1. Resveratrol treatment reveals a novel role for HMGB1 in regulation of the type 1 interferon response in dengue virus infection.

    Science.gov (United States)

    Zainal, Nurhafiza; Chang, Chih-Peng; Cheng, Yi-Lin; Wu, Yan-Wei; Anderson, Robert; Wan, Shu-Wen; Chen, Chia-Ling; Ho, Tzong-Shiann; AbuBakar, Sazaly; Lin, Yee-Shin

    2017-02-20

    Dengue is one of the most significant mosquito-borne virus diseases worldwide, particularly in tropical and subtropical regions. This study sought to examine the antiviral activity of resveratrol (RESV), a phytoalexin secreted naturally by plants, against dengue virus (DENV) infection. Our data showed that RESV inhibits the translocation of high mobility group box 1 (HMGB1), a DNA binding protein that normally resides in the nucleus, into the cytoplasm and extracellular milieu. HMGB1 migrates out of the nucleus during DENV infection. This migration is inhibited by RESV treatment and is mediated by induction of Sirt1 which leads to the retention of HMGB1 in the nucleus and consequently helps in the increased production of interferon-stimulated genes (ISGs). Nuclear HMGB1 was found to bind to the promoter region of the ISG and positively regulated the expression of ISG. The enhanced transcription of ISGs by nuclear HMGB1 thus contributes to the antiviral activity of RESV against DENV. To the best of our knowledge, this is the first report to demonstrate that RESV antagonizes DENV replication and that nuclear HMGB1 plays a role in regulating ISG production.

  2. MicroRNA, SND1, and alterations in translational regulation in colon carcinogenesis

    International Nuclear Information System (INIS)

    Tsuchiya, Naoto; Nakagama, Hitoshi

    2010-01-01

    Post-transcriptional regulation of gene expression by microRNA (miRNA) has recently attracted major interest in relation to its involvement in cancer development. miRNA is a member of small non-coding RNA, consists of 22-24 nucleotides and regulates expression of target mRNA species in a post-transcriptional manner by being incorporated with RNA-induced silencing complex (RISC). Staphylococcal nuclease homology domain containing 1 (SND1), a component of RISC, is frequently up-regulated in human colon cancers and also chemically induced colon cancers in animals. We here showed that SDN1 is involved in miRNA-mediated gene suppression and overexpression of SND1 in colon cancer cells causes down-regulation of APC without altering APC mRNA levels. As for the miRNA expression profile in human colon cancer, miR-34a was among the list of down-regulated miRNA. Expression of miR-34a is tightly regulated by p53, and ectopic expression of miR-34a in colon cancer cells causes remarkable reduction of cell proliferation and induces senescence-like phenotypes. MiR-34a also participates in the positive feedback loop of the p53 tumor suppressor network. This circuitry mechanism for p53 activation is of interest in understanding the tumor suppressive function of miR-34a in colon carcinogenesis. miRNA should also be considered as novel anti-cancer agents in tumor suppressive therapeutic applications.

  3. Polymorphism of human haptoglobin and its clinical importance

    Directory of Open Access Journals (Sweden)

    Vânia Peretti de Albuquerque Wobeto

    2008-01-01

    Full Text Available Haptoglobin (Hp is a plasma glycoprotein, the main biological function of which is to bind free hemoglobin (Hb and prevent the loss of iron and subsequent kidney damage following intravascular hemolysis. Haptoglobin is also a positive acute-phase protein with immunomodulatory properties. In humans, the HP locus is polymorphic, with two codominant alleles (HP1 and HP2 that yield three distinct genotypes/phenotypes (Hp1-1, Hp2-1 and Hp2-2. The corresponding proteins have structural and functional differences that may influence the susceptibility and/or outcome in several diseases. This article summarizes the available data on the structure and functions of Hp and the possible effects of Hp polymorphism in a number of important human disorders.

  4. Up-regulation of CHAF1A, a poor prognostic factor, facilitates cell proliferation of colon cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Zehua; Cui, Feifei; Yu, Fudong; Peng, Xiao; Jiang, Tao; Chen, Dawei [Department of General Surgery, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080 (China); Lu, Su [Department of Pathology, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080 (China); Tang, Huamei, E-mail: tanghuamei@gmail.com [Department of Pathology, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080 (China); Peng, Zhihai, E-mail: zhihai.peng@hotmail.com [Department of General Surgery, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080 (China)

    2014-06-27

    Highlights: • We identified that CHAF1A was up-regulated in colon tumor mucosa in TMA. • The expression pattern of CHAF1A was validated with qPCR and western-blot. • CHAF1A overexpression is an independent indicator for poor colon cancer survival. • CHAF1A facilitates cell proliferation of colon cancer both in vitro and in vivo. - Abstract: Deregulation of chromatin assembly factor 1, p150 subunit A (CHAF1A) has recently been reported to be involved in the development of some cancer types. In this study, we identified that the frequency of positive CHAF1A staining in primary tumor mucosa (45.8%, 93 of 203 samples) was significantly elevated compared to that in paired normal mucosa (18.7%, 38 of 203 samples). The increased expression was strongly associated with cancer stage, tumor invasion, and histological grade. The five-year survival rate of patients with CHAF1A-positive tumors was remarkably lower than that of patients with CHAF1A-negative tumors. Colon cancer cells with CHAF1A knockdown exhibited decreased cell growth index, reduction in colony formation ability, elevated cell apoptosis rate as well as impaired colon tumorigenicity in nude mice. Hence, CHAF1A upregulation functions as a poor prognostic indicator of colon cancer, potentially contributing to its progression by mediating cancer cell proliferation.

  5. Up-regulation of CHAF1A, a poor prognostic factor, facilitates cell proliferation of colon cancer

    International Nuclear Information System (INIS)

    Wu, Zehua; Cui, Feifei; Yu, Fudong; Peng, Xiao; Jiang, Tao; Chen, Dawei; Lu, Su; Tang, Huamei; Peng, Zhihai

    2014-01-01

    Highlights: • We identified that CHAF1A was up-regulated in colon tumor mucosa in TMA. • The expression pattern of CHAF1A was validated with qPCR and western-blot. • CHAF1A overexpression is an independent indicator for poor colon cancer survival. • CHAF1A facilitates cell proliferation of colon cancer both in vitro and in vivo. - Abstract: Deregulation of chromatin assembly factor 1, p150 subunit A (CHAF1A) has recently been reported to be involved in the development of some cancer types. In this study, we identified that the frequency of positive CHAF1A staining in primary tumor mucosa (45.8%, 93 of 203 samples) was significantly elevated compared to that in paired normal mucosa (18.7%, 38 of 203 samples). The increased expression was strongly associated with cancer stage, tumor invasion, and histological grade. The five-year survival rate of patients with CHAF1A-positive tumors was remarkably lower than that of patients with CHAF1A-negative tumors. Colon cancer cells with CHAF1A knockdown exhibited decreased cell growth index, reduction in colony formation ability, elevated cell apoptosis rate as well as impaired colon tumorigenicity in nude mice. Hence, CHAF1A upregulation functions as a poor prognostic indicator of colon cancer, potentially contributing to its progression by mediating cancer cell proliferation

  6. Publication of the safety regulation KTA 3603 of the Committee for Nuclear Technology (KTA)

    International Nuclear Information System (INIS)

    1980-01-01

    The regulation applies to the planning, construction and operation of plants for the treatment of radioactive, contaminated water from stationary nuclear power plants with LWR- and HTR-type reactors. According to the regulation, plants for the treatment of contaminated natur are to be planned, constructed, and operated in such a way that - uncontrolled discharge of contaminated water will be avoided (article 46, paragraph 1, no. 1 StrlSchV), - the activity discharged with water is as low as possible (article 46, paragraph 1, no. 2 StrlSchV), - radioactive contaminated water will not be discharged into the ground, - personnel exposure due to direct radiation, contamination, and inhalation will be as low as possible even below the limiting values fixed in the Radiation Protection Ordinance (article 28, paragraph 1 StrlSchV). Furthermore, discharge of liquid waste into bodies of water requires special permission (articles 2, 3, 7 WHG). (orig./HP) [de

  7. An hp-adaptive strategy for the solution of the exact kernel curved wire Pocklington equation

    NARCIS (Netherlands)

    D.J.P. Lahaye (Domenico); P.W. Hemker (Piet)

    2007-01-01

    textabstractIn this paper we introduce an adaptive method for the numerical solution of the Pocklington integro-differential equation with exact kernel for the current induced in a smoothly curved thin wire antenna. The hp-adaptive technique is based on the representation of the discrete solution,

  8. A novel role of Yin-Yang-1 in pulmonary tuberculosis through the regulation of the chemokine CCL4.

    Science.gov (United States)

    Rangel-Santiago, Jesus F; Baay-Guzman, Guillermina J; Duran-Padilla, Marco A; Lopez-Bochm, Karla A; Garcia-Romero, Beatriz L; Hernandez-Cueto, Daniel D; Pantoja-Escobar, Gerardo; Vega, Mario I; Hernandez-Pando, Rogelio; Huerta-Yepez, Sara

    2016-01-01

    Mycobacterium tuberculosis (M. tb) is the etiological agent of pulmonary tuberculosis (TB); this disease remains a worldwide health problem. Yin-Yang-1 (YY1) plays a major role in the maintenance and progression of some pulmonary diseases, including pulmonary fibrosis. However, the role of YY1 in TB remains unknown. The aim of this study was to elucidate the role of YY1 in the regulation of CCL4 and its implication in TB. We determined whether YY1 regulates CCL4 using reporter plasmids, ChIP and siRNA assays. Immunohistochemistry and digital pathology were used to measure the expression of YY1 and CCL4 in a mouse model of TB. A retrospective comparison of patients with TB and control subjects was used to measure the expression of YY1 and CCL4 using tissue microarrays. Our results showed that YY1 regulates the transcription of CCL4; moreover, YY1, CCL4 and TGF-β were overexpressed in the lung tissues of mice with TB during the late stages of the disease and the tissues of TB patients. The expression of CCL4 and TGF-β correlated with YY1 expression. In conclusion, YY1 regulates CCL4 transcription; moreover, YY1 is overexpressed in experimental and human TB and is positively correlated with CCL4 and TGF-β expression. Therefore, treatments that decrease YY1 expression may be a new therapeutic strategy against TB. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Mothering, fathering, and the regulation of negative and positive emotions in high-functioning preschoolers with autism spectrum disorder.

    Science.gov (United States)

    Hirschler-Guttenberg, Yael; Golan, Ofer; Ostfeld-Etzion, Sharon; Feldman, Ruth

    2015-05-01

    Children with autism spectrum disorder (ASD) exhibit difficulties in regulating emotions and authors have called to study the specific processes underpinning emotion regulation (ER) in ASD. Yet, little observational research examined the strategies preschoolers with ASD use to regulate negative and positive emotions in the presence of their mothers and fathers. Forty preschoolers with ASD and 40 matched typically developing children and their mothers and fathers participated. Families were visited twice for identical battery of paradigms with mother or father. Parent-child interactions were coded for parent and child behaviors and children engaged in ER paradigms eliciting negative (fear) and positive (joy) emotions with each parent. ER paradigms were microcoded for negative and positive emotionality, ER strategies, and parent regulation facilitation. During free play, mothers' and fathers' sensitivity and warm discipline were comparable across groups; however, children with ASD displayed lower positive engagement and higher withdrawal. During ER paradigms, children with ASD expressed less positive emotionality overall and more negative emotionality during fear with father. Children with ASD used more simple self-regulatory strategies, particularly during fear, but expressed comparable levels of assistance seeking behavior toward mother and father in negative and positive contexts. Parents of children with ASD used less complex regulation facilitation strategies, including cognitive reappraisal and emotional reframing, and employed simple tactics, such as physical comforting to manage fear and social gaze to maintain joy. Findings describe general and parent- and emotion-specific processes of child ER and parent regulation facilitation in preschoolers with ASD. Results underscore the ability of such children to seek parental assistance during moments of high arousal and the parents' sensitive adaptation to their children's needs. Reduced positive emotionality

  10. IGF-I: A key growth factor that regulates neurogenesis and synaptogenesis from embryonic to adult stages of the brain

    Directory of Open Access Journals (Sweden)

    Vanesa eNieto-Estévez

    2016-02-01

    Full Text Available The generation of neurons in the adult mammalian brain requires the activation of quiescent neural stem cells (NSCs. This activation and the sequential steps of neuron formation from NSCs are regulated by a number of stimuli, which include growth factors. Insulin-like growth factor-I (IGF-I exert pleiotropic effects, regulating multiple cellular processes depending on their concentration, cell type and the developmental stage of the animal. Although IGF-I expression is relatively high in the embryonic brain its levels drop sharply in the adult brain except in neurogenic regions, i.e., the hippocampus (HP and the subventricular zone-olfactory bulb (SVZ-OB. By contrast, the expression of IGF-IR remains relatively high in the brain irrespective of the age of the animal. Evidence indicates that IGF-I influences NSC proliferation and differentiation into neurons and glia as well as neuronal maturation including synapse formation. Furthermore, recent studies have shown that IGF-I not only promote adult neurogenesis by regulating NSC number and differentiation but also, by influencing neuronal positioning and migration as described during SVZ-OB neurogenesis. In this article we will revise and discuss the actions reported for IGF-I signaling in a variety of in vitro and in vivo models, focusing on the maintenance and proliferation of NSCs/progenitors, neurogenesis and neuron integration in synaptic circuits.

  11. IGF-I: A Key Growth Factor that Regulates Neurogenesis and Synaptogenesis from Embryonic to Adult Stages of the Brain

    Science.gov (United States)

    Nieto-Estévez, Vanesa; Defterali, Çağla; Vicario-Abejón, Carlos

    2016-01-01

    The generation of neurons in the adult mammalian brain requires the activation of quiescent neural stem cells (NSCs). This activation and the sequential steps of neuron formation from NSCs are regulated by a number of stimuli, which include growth factors. Insulin-like growth factor-I (IGF-I) exert pleiotropic effects, regulating multiple cellular processes depending on their concentration, cell type, and the developmental stage of the animal. Although IGF-I expression is relatively high in the embryonic brain its levels drop sharply in the adult brain except in neurogenic regions, i.e., the hippocampus (HP) and the subventricular zone-olfactory bulb (SVZ-OB). By contrast, the expression of IGF-IR remains relatively high in the brain irrespective of the age of the animal. Evidence indicates that IGF-I influences NSC proliferation and differentiation into neurons and glia as well as neuronal maturation including synapse formation. Furthermore, recent studies have shown that IGF-I not only promote adult neurogenesis by regulating NSC number and differentiation but also by influencing neuronal positioning and migration as described during SVZ-OB neurogenesis. In this article we will revise and discuss the actions reported for IGF-I signaling in a variety of in vitro and in vivo models, focusing on the maintenance and proliferation of NSCs/progenitors, neurogenesis, and neuron integration in synaptic circuits. PMID:26941597

  12. A detector system for two-dimensional, position-sensitive detection of neutrons and gamma quanta

    International Nuclear Information System (INIS)

    Scholz, A.

    1988-08-01

    While the well-known Anger Camera utilizes a large number of photomultiplier tubes, which are arranged in a regular array behind a scintillation crystal, the new detector system makes use of electron optics to transfer the scintillation image of a large scintillation crystal (Li-6-glass) onto a small position detector. Because of this, only few photodetectors are required for position readout, associated with only a small number of amplifier chains and a very simple position reconstruction algorithm. The reduced complexity of the readout electronics ultimately leads to an improved maintainability and reliability of the detector system. A prototype of the new detector system was built and tested. After giving an overview on already known and realized detector configurations, the basic considerations, which led to the final detector design, will be explained. Different methods of detector readout and position determination are discussed. Measurement results which were obtained with the prototype detector system are presented and explained by means of simulation calculations. (orig./HP) [de

  13. Enhanced transpiration rate in the high pigment 1 tomato mutant and its physiological significance.

    Science.gov (United States)

    Carvalho, R F; Aidar, S T; Azevedo, R A; Dodd, I C; Peres, L E P

    2011-05-01

    Tomato high pigment (hp) mutants represent an interesting horticultural resource due to their enhanced accumulation of carotenoids, flavonoids and vitamin C. Since hp mutants are known for their exaggerated light responses, the molecules accumulated are likely to be antioxidants, recruited to deal with light and others stresses. Further phenotypes displayed by hp mutations are reduced growth and an apparent disturbance in water loss. Here, we examined the impact of the hp1 mutation and its near isogenic line cv Micro-Tom (MT) on stomatal conductance (gs), transpiration (E), CO(2) assimilation (A) and water use efficiency (WUE). Detached hp1 leaves lost water more rapidly than control leaves, but this behaviour was reversed by exogenous abscisic acid (ABA), indicating the ability of hp1 to respond to this hormone. Although attached hp1 leaves had enhanced gs, E and A compared to control leaves, genotypic differences were lost when water was withheld. Both instantaneous leaf-level WUE and long-term whole plant WUE did not differ between hp1 and MT. Our results indicate a link between exaggerated light response and water loss in hp1, which has important implications for the use of this mutant in both basic and horticultural research. © 2011 German Botanical Society and The Royal Botanical Society of the Netherlands.

  14. Rapamycin up-regulates triglycerides in hepatocytes by down-regulating Prox1.

    Science.gov (United States)

    Kwon, Sora; Jeon, Ji-Sook; Kim, Su Bin; Hong, Young-Kwon; Ahn, Curie; Sung, Jung-Suk; Choi, Inho

    2016-02-27

    Although the prolonged use of rapamycin may cause unwanted side effects such as hyperlipidemia, the underlying mechanism remains unknown. Prox1 is a transcription factor responsible for the development of several tissues including lymphatics and liver. There is growing evidences that Prox1 participates in metabolism in addition to embryogenesis. However, whether Prox1 is directly related to lipid metabolism is currently unknown. HepG2 human hepatoma cells were treated with rapamycin and total lipids were analyzed by thin layer chromatography. The effect of rapamycin on the expression of Prox1 was determined by western blotting. To investigate the role of Prox1 in triglycerides regulation, siRNA and overexpression system were employed. Rapamycin was injected into mice for 2 weeks and total lipids and proteins in liver were measured by thin layer chromatography and western blot analysis, respectively. Rapamycin up-regulated the amount of triglyceride and down-regulated the expression of Prox1 in HepG2 cells by reducing protein half-life but did not affect its transcript. The loss-of-function of Prox1 was coincident with the increase of triglycerides in HepG2 cells treated with rapamycin. The up-regulation of triglycerides by rapamycin in HepG2 cells reverted to normal levels by the compensation of Prox1 using the overexpression system. Rapamycin also down-regulated Prox1 expression but increased triglycerides in mouse liver. This study suggests that rapamycin can increase the amount of triglycerides by down-regulating Prox1 expression in hepatocytes, which means that the mammalian target of rapamycin (mTOR) signaling is important for the regulation of triglycerides by maintaining Prox1 expression.

  15. The accident prevention regulation 'Thermal Power Stations' and its effects in practice

    International Nuclear Information System (INIS)

    Albert, O.

    1983-01-01

    The origin of the accident prevention regulation - ''Thermal Power Stations'' is attributable mainly to two tragic accidents. It has made organizational changes and interventions in the operational process necessary in thermal power stations. Emphasis is laid upon the consistent issue of written permits-to-work on plant components carrying a heating medium and operating under pressure and on written operating licences for the operation of boilers. The paper describes additional ways in which regulation influences the daily practices of the power station operator. Brief references is made to the draft of the revised regulation. (orig./HP) [de

  16. Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic beta cells.

    Directory of Open Access Journals (Sweden)

    Laura Bordone

    2006-02-01

    Full Text Available Sir2 and insulin/IGF-1 are the major pathways that impinge upon aging in lower organisms. In Caenorhabditis elegans a possible genetic link between Sir2 and the insulin/IGF-1 pathway has been reported. Here we investigate such a link in mammals. We show that Sirt1 positively regulates insulin secretion in pancreatic beta cells. Sirt1 represses the uncoupling protein (UCP gene UCP2 by binding directly to the UCP2 promoter. In beta cell lines in which Sirt1 is reduced by SiRNA, UCP2 levels are elevated and insulin secretion is blunted. The up-regulation of UCP2 is associated with a failure of cells to increase ATP levels after glucose stimulation. Knockdown of UCP2 restores the ability to secrete insulin in cells with reduced Sirt1, showing that UCP2 causes the defect in glucose-stimulated insulin secretion. Food deprivation induces UCP2 in mouse pancreas, which may occur via a reduction in NAD (a derivative of niacin levels in the pancreas and down-regulation of Sirt1. Sirt1 knockout mice display constitutively high UCP2 expression. Our findings show that Sirt1 regulates UCP2 in beta cells to affect insulin secretion.

  17. DBC1 promotes castration-resistant prostate cancer by positively regulating DNA binding and stability of AR-V7.

    Science.gov (United States)

    Moon, Sue Jin; Jeong, Byong Chang; Kim, Hwa Jin; Lim, Joung Eun; Kwon, Ghee Young; Kim, Jeong Hoon

    2018-03-01

    Constitutively active AR-V7, one of the major androgen receptor (AR) splice variants lacking the ligand-binding domain, plays a key role in the development of castration-resistant prostate cancer (CRPC) and anti-androgen resistance. However, our understanding of the regulatory mechanisms of AR-V7-driven transcription is limited. Here we report DBC1 as a key regulator of AR-V7 transcriptional activity and stability in CRPC cells. DBC1 functions as a coactivator for AR-V7 and is required for the expression of AR-V7 target genes including CDH2, a mesenchymal marker linked to CRPC progression. DBC1 is required for recruitment of AR-V7 to its target enhancers and for long-range chromatin looping between the CDH2 enhancer and promoter. Mechanistically, DBC1 enhances DNA-binding activity of AR-V7 by direct interaction and inhibits CHIP E3 ligase-mediated ubiquitination and degradation of AR-V7 by competing with CHIP for AR-V7 binding, thereby stabilizing and activating AR-V7. Importantly, DBC1 depletion suppresses the tumorigenic and metastatic properties of CRPC cells. Our results firmly establish DBC1 as a critical AR-V7 coactivator that plays a key role in the regulation of DNA binding and stability of AR-V7 and has an important physiological role in CRPC progression.

  18. Global regulator SATB1 recruits beta-catenin and regulates T(H2 differentiation in Wnt-dependent manner.

    Directory of Open Access Journals (Sweden)

    Dimple Notani

    2010-01-01

    Full Text Available In vertebrates, the conserved Wnt signalling cascade promotes the stabilization and nuclear accumulation of beta-catenin, which then associates with the lymphoid enhancer factor/T cell factor proteins (LEF/TCFs to activate target genes. Wnt/beta -catenin signalling is essential for T cell development and differentiation. Here we show that special AT-rich binding protein 1 (SATB1, the T lineage-enriched chromatin organizer and global regulator, interacts with beta-catenin and recruits it to SATB1's genomic binding sites. Gene expression profiling revealed that the genes repressed by SATB1 are upregulated upon Wnt signalling. Competition between SATB1 and TCF affects the transcription of TCF-regulated genes upon beta-catenin signalling. GATA-3 is a T helper type 2 (T(H2 specific transcription factor that regulates production of T(H2 cytokines and functions as T(H2 lineage determinant. SATB1 positively regulated GATA-3 and siRNA-mediated knockdown of SATB1 downregulated GATA-3 expression in differentiating human CD4(+ T cells, suggesting that SATB1 influences T(H2 lineage commitment by reprogramming gene expression. In the presence of Dickkopf 1 (Dkk1, an inhibitor of Wnt signalling, GATA-3 is downregulated and the expression of signature T(H2 cytokines such as IL-4, IL-10, and IL-13 is reduced, indicating that Wnt signalling is essential for T(H2 differentiation. Knockdown of beta-catenin also produced similar results, confirming the role of Wnt/beta-catenin signalling in T(H2 differentiation. Furthermore, chromatin immunoprecipitation analysis revealed that SATB1 recruits beta-catenin and p300 acetyltransferase on GATA-3 promoter in differentiating T(H2 cells in a Wnt-dependent manner. SATB1 coordinates T(H2 lineage commitment by reprogramming gene expression. The SATB1:beta-catenin complex activates a number of SATB1 regulated genes, and hence this study has potential to find novel Wnt responsive genes. These results demonstrate that SATB1

  19. Increased plasma ghrelin suppresses insulin release in wethers fed with a high-protein diet.

    Science.gov (United States)

    Takahashi, T; Sato, K; Kato, S; Yonezawa, T; Kobayashi, Y; Ohtani, Y; Ohwada, S; Aso, H; Yamaguchi, T; Roh, S G; Katoh, K

    2014-06-01

    Ghrelin is a multifunctional peptide that promotes an increase of food intake and stimulates GH secretion. Ghrelin secretion is regulated by nutritional status and nutrients. Although a high-protein (HP) diet increases plasma ghrelin secretion in mammals, the mechanisms and the roles of the elevated ghrelin concentrations due to a HP diet have not been fully established. To clarify the roles of elevated acylated ghrelin upon intake of a HP diet, we investigated the regulation of ghrelin concentrations in plasma and tissues in wethers fed with either the HP diet or the control (CNT) diet for 14 days, and examined the action of the elevated plasma ghrelin by using a ghrelin-receptor antagonist. The HP diet gradually increased the plasma acylated-ghrelin concentrations, but the CNT diet did not. Although the GH concentrations did not vary significantly across the groups, an injection of ghrelin-receptor antagonist enhanced insulin levels in circulation in the HP diet group. In the fundus region of the stomach, the ghrelin levels did not differ between the HP and CNT diet groups, whereas ghrelin O-acyltransferase mRNA levels were higher in the group fed with HP diet than those of the CNT diet group were. These results indicate that the HP diet elevated the plasma ghrelin levels by increasing its synthesis; this elevation strongly suppresses the appearance of insulin in the circulation of wethers, but it is not involved in GH secretion. Overall, our findings indicate a role of endogenous ghrelin action in secretion of insulin, which acts as a regulator after the consumption of a HP diet. © 2014 Society for Endocrinology.

  20. Positive and Negative Associations between Adolescents’ Religiousness and Health Behaviors via Self-Regulation

    Science.gov (United States)

    Holmes, Christopher J.; Kim-Spoon, Jungmeen

    2015-01-01

    It has been proposed that self-regulation may be the explanatory mechanism for the relation between religiousness and positive health behaviors. However, different religious motivations have differential effects on a variety of health related outcomes, which may explain the adverse effects of religiousness found in some studies. The current study hypothesized that higher identification as religious motivation would be linked to higher health-promoting behavior and lower health-risk behavior through higher self-regulation, whereas higher introjection would be linked to lower health-promoting behavior and higher health-risk behavior through lower self-regulation. The sample included 220 adolescents (mean age = 15 years, 55% male) and their primary caregivers. Structural equation modeling results supported the hypotheses and indicated that adolescent self-regulation mediated the relations between their religious motivation and health behavior. The findings suggest that different types of religious motivation may be promotive or hindering for adolescents’ health. PMID:27595048