WorldWideScience

Sample records for r factors

  1. Factor Analysis Using "R"

    Science.gov (United States)

    Beaujean, A. Alexander

    2013-01-01

    "R" (R Development Core Team, 2011) is a very powerful tool to analyze data, that is gaining in popularity due to its costs (its free) and flexibility (its open-source). This article gives a general introduction to using "R" (i.e., loading the program, using functions, importing data). Then, using data from Canivez, Konold, Collins, and Wilson…

  2. Factor Analysis Using "R"

    Science.gov (United States)

    Beaujean, A. Alexander

    2013-01-01

    "R" (R Development Core Team, 2011) is a very powerful tool to analyze data, that is gaining in popularity due to its costs (its free) and flexibility (its open-source). This article gives a general introduction to using "R" (i.e., loading the program, using functions, importing data). Then, using data from Canivez, Konold, Collins, and Wilson…

  3. R-Factor for Alaska

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The rainfall-runoff erosivity factor (R-Factor) quantifies the effects of raindrop impacts and reflects the amount and rate of runoff associated with the rain. The...

  4. Multiple factor analysis by example using R

    CERN Document Server

    Pagès, Jérôme

    2014-01-01

    Multiple factor analysis (MFA) enables users to analyze tables of individuals and variables in which the variables are structured into quantitative, qualitative, or mixed groups. Written by the co-developer of this methodology, Multiple Factor Analysis by Example Using R brings together the theoretical and methodological aspects of MFA. It also includes examples of applications and details of how to implement MFA using an R package (FactoMineR).The first two chapters cover the basic factorial analysis methods of principal component analysis (PCA) and multiple correspondence analysis (MCA). The

  5. On R factors for dynamic structure crystallography

    DEFF Research Database (Denmark)

    Coppens, Philip; Kaminski, Radoslaw; Schmøkel, Mette Stokkebro

    2010-01-01

    In studies of dynamic changes in crystals in which induced metastable species may have lifetimes of microseconds or less, refinements are most sensitive if based on the changes induced in the measured intensities. Agreement factors appropriate for such refinements, based on the ratios of the inte...... of the intensities before and after the external perturbation is applied, are discussed and compared with R factors commonly applied in static structure crystallography....

  6. Extrachromosomal deoxyribonucleic acid in R factor-harboring Enterobacteriaceae

    DEFF Research Database (Denmark)

    Møller, JK; Bak, AL; Christiansen, C

    1976-01-01

    Extrachromosomal deoxyribonucleic acid (DNA) from 24 different R factor-harboring Enterobacteriaceae was isolated and characterized by analytical ultracentrifugation and electron microscopy. The R factors represented 15 different patterns of transferable drug resistance found in enterobacteria from...... from 1.700 to 1.720 g/cm3. The majority of the bacteria contained extrachromosomal DNAs of various densities. Three-fourths of the R factors were classified as fi+. The investigation illustrates the extensive variability in the physical characteristics of plasmid DNA from R factor-harboring strains....

  7. R-Factor for the Coterminous United States

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The rainfall-runoff erosivity factor (R-Factor) quantifies the effects of raindrop impacts and reflects the amount and rate of runoff associated with the rain. The...

  8. R-Factor for the Island of Puerto Rico

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The rainfall-runoff erosivity factor (R-Factor) quantifies the effects of raindrop impacts and reflects the amount and rate of runoff associated with the rain. The...

  9. R-Factor for the Island of Lanai

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The rainfall-runoff erosivity factor (R-Factor) quantifies the effects of raindrop impacts and reflects the amount and rate of runoff associated with the rain. The...

  10. R-Factor for the Island of Kauai

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The rainfall-runoff erosivity factor (R-Factor) quantifies the effects of raindrop impacts and reflects the amount and rate of runoff associated with the rain. The...

  11. R-Factor for the Island of Molokai

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The rainfall-runoff erosivity factor (R-Factor) quantifies the effects of raindrop impacts and reflects the amount and rate of runoff associated with the rain. The...

  12. R-Factor for the Island of Oahu

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The rainfall-runoff erosivity factor (R-Factor) quantifies the effects of raindrop impacts and reflects the amount and rate of runoff associated with the rain. The...

  13. R-Factor for the Island of Maui

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The rainfall-runoff erosivity factor (R-Factor) quantifies the effects of raindrop impacts and reflects the amount and rate of runoff associated with the rain. The...

  14. R-Factor for the Island of Hawaii

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The rainfall-runoff erosivity factor (R-Factor) quantifies the effects of raindrop impacts and reflects the amount and rate of runoff associated with the rain. The...

  15. How the R factor changes as molecules become larger

    DEFF Research Database (Denmark)

    Krebs, Frederik C

    2000-01-01

    The R factors and the numbers of independent atoms for the entire set of molecular organic structures contained in the Cambridge Structural Database were retrieved and analysed. The average R factor for all structures containing the same number of independent atoms was plotted against the number...... of independent atoms. A clear correlation was observed. The plot is suggested to give a graphical overview of how values of the R factor for large-molecule structures with 200-1000 independent atoms increase as the number of independent atoms increases. (C) 2000 International Union of Crystallography Printed...

  16. A new role for plant R2R3-MYB transcription factors in cell cycle regulation

    Institute of Scientific and Technical Information of China (English)

    Eleonora Cominelli; Chiara Tonelli

    2009-01-01

    @@ MYB proteins are transcription factors present in all eukaryotes,sharing a common DNA-binding domain that consists of one to three imperfect helix-helix-turn-helix repeats of about 50 amino acids,called RI,R2,and R3 respectively [1].In animals and yeast these proteins represent a small gene family [1].Animal R1R2R3-MYB proteins have been described for their role in cell cycle regulation mainly at the G1/S,but also at the G2/M transition,as firstly demonstrated in Drosophila [2].

  17. An R2R3-MYB Transcription Factor Regulates Capsaicinoid Biosynthesis.

    Science.gov (United States)

    Arce-Rodríguez, Magda L; Ochoa-Alejo, Neftalí

    2017-07-01

    Capsaicinoids are responsible for the hot taste of chili peppers. They are restricted to the genus Capsicum and are synthesized by the acylation of the aromatic compound vanillylamine (derived from the phenylpropanoid pathway) with a branched-chain fatty acid by the catalysis of the putative enzyme capsaicinoid synthase. R2R3-MYB transcription factors have been reported in different species of plants as regulators of structural genes of the phenylpropanoid pathway; therefore, we hypothesized that MYB genes might be involved in the regulation of the biosynthesis of pungent compounds. In this study, an R2R3-MYB transcription factor gene, designated CaMYB31, was isolated and characterized in Capsicum annuum 'Tampiqueño 74'. Bioinformatic analysis suggested that CaMYB31 could be involved in secondary metabolism, stress and plant hormone responses, and development. CaMYB31 expression analysis from placental tissue of pungent and nonpungent chili pepper fruits showed a positive correlation with the structural genes Ca4H, Comt, Kas, pAmt, and AT3 expression and also with the content of capsaicin and dihydrocapsacin during fruit development. However, CaMYB31 also was expressed in vegetative tissues (leaves, roots, and stems). Moreover, CaMYB31 silencing significantly reduced the expression of capsaicinoid biosynthetic genes and the capsaicinoid content. Additionally, CaMYB31 expression was affected by the plant hormones indoleacetic acid, jasmonic acid, salicylic acid, and gibberellic acid or by wounding, temperature, and light, factors known to affect the production of capsaicinoids. These findings indicate that CaMYB31 is indeed involved in the regulation of structural genes of the capsaicinoid biosynthetic pathway. © 2017 American Society of Plant Biologists. All Rights Reserved.

  18. An R2R3-MYB Transcription Factor Regulates Capsaicinoid Biosynthesis1[OPEN

    Science.gov (United States)

    Arce-Rodríguez, Magda L.

    2017-01-01

    Capsaicinoids are responsible for the hot taste of chili peppers. They are restricted to the genus Capsicum and are synthesized by the acylation of the aromatic compound vanillylamine (derived from the phenylpropanoid pathway) with a branched-chain fatty acid by the catalysis of the putative enzyme capsaicinoid synthase. R2R3-MYB transcription factors have been reported in different species of plants as regulators of structural genes of the phenylpropanoid pathway; therefore, we hypothesized that MYB genes might be involved in the regulation of the biosynthesis of pungent compounds. In this study, an R2R3-MYB transcription factor gene, designated CaMYB31, was isolated and characterized in Capsicum annuum ‘Tampiqueño 74’. Bioinformatic analysis suggested that CaMYB31 could be involved in secondary metabolism, stress and plant hormone responses, and development. CaMYB31 expression analysis from placental tissue of pungent and nonpungent chili pepper fruits showed a positive correlation with the structural genes Ca4H, Comt, Kas, pAmt, and AT3 expression and also with the content of capsaicin and dihydrocapsacin during fruit development. However, CaMYB31 also was expressed in vegetative tissues (leaves, roots, and stems). Moreover, CaMYB31 silencing significantly reduced the expression of capsaicinoid biosynthetic genes and the capsaicinoid content. Additionally, CaMYB31 expression was affected by the plant hormones indoleacetic acid, jasmonic acid, salicylic acid, and gibberellic acid or by wounding, temperature, and light, factors known to affect the production of capsaicinoids. These findings indicate that CaMYB31 is indeed involved in the regulation of structural genes of the capsaicinoid biosynthetic pathway. PMID:28483879

  19. Latent Constructs of the Static-99R and Static-2002R: A Three-Factor Solution.

    Science.gov (United States)

    Brouillette-Alarie, Sébastien; Babchishin, Kelly M; Hanson, R Karl; Helmus, Leslie-Maaike

    2016-02-01

    The most commonly used risk assessment tools for predicting sexual violence focus almost exclusively on static, historical factors (e.g., characteristics of prior offences). Consequently, they are assumed to be unable to directly inform the selection of treatment targets or evaluate change. In this article, we argue that this limitation can be mitigated by using latent variable models as a framework to link historical risk factors to the psychological characteristics of offenders. Accordingly, we conducted a factor analysis of the 13 nonredundant items from the two most commonly used risk tools for sexual offenders (Static-99R and Static-2002R) to identify the psychological information contained in these tools. Three factors were identified: (a) persistence/paraphilia, a construct related to sexual criminality, especially of the pedophilic type; (b) youthful stranger aggression, a construct centered on young age and offence seriousness; and (c) general criminality, a construct that reflected the diversity and magnitude of criminal careers. These constructs predicted sexual recidivism with similar accuracy, but only youthful stranger aggression and general criminality predicted nonsexual recidivism. These results indicate that risk tools for sexual violence are multidimensional, and support a shift from a focus on atheoretical risk markers to the assessment of psychologically meaningful constructs.

  20. A sugarcane R2R3-MYB transcription factor gene is alternatively spliced during drought stress

    Science.gov (United States)

    Guo, Jinlong; Ling, Hui; Ma, Jingjing; Chen, Yun; Su, Yachun; Lin, Qingliang; Gao, Shiwu; Wang, Hengbo; Que, Youxiong; Xu, Liping

    2017-01-01

    MYB transcription factors of the R2R3-MYB family have been shown to play important roles in many plant processes. A sugarcane R2R3-MYB gene (ScMYB2) and its two alternative forms of transcript (ScMYB2S1 and ScMYB2S2) were identified in this study. The deduced protein of ScMYB2S1 is a typical plant R2R3-MYB protein, while ScMYB2S2 encodes a truncated protein. Real-time qPCR analysis revealed that ScMYB2S1 is suppressed under PEG-simulated drought stress in sugarcane, while ScMYB2S2 is induced at later treatment stage. A senescence symptom was observed when ScMYB2S1 was injected into tobacco leaves mediated by Agrobacterium, but no symptom for ScMYB2S2. Further investigation showed that the expression levels of 4 senescence-associated genes, NtPR-1a, NtNYC1, NtCAT3 and NtABRE, were markedly induced in tobacco leaves after ScMYB2S1-injection, while they were not sensitive to ScMYB2S2-injection. Moreover, MDA and proline were also investigated after injection. Similarly, MDA and proline levels were induced by ABA and ScMYB2S1, while inhibited by ScMYB2S2. We propose that ScMYB2, by alternatively splicing two transcripts (ScMYB2S1 and ScMYB2S2), is involved in an ABA-mediated leaf senescence signaling pathway and play positive role in respond to drought-induced senescence in sugarcane. The results of this study provide information for further research in sugarcane stress processes. PMID:28167824

  1. An R2R3-MYB Transcription Factor Regulates Eugenol Production in Ripe Strawberry Fruit Receptacles.

    Science.gov (United States)

    Medina-Puche, Laura; Molina-Hidalgo, Francisco Javier; Boersma, Maaike; Schuurink, Robert C; López-Vidriero, Irene; Solano, Roberto; Franco-Zorrilla, José-Manuel; Caballero, José Luis; Blanco-Portales, Rosario; Muñoz-Blanco, Juan

    2015-06-01

    Eugenol is a volatile phenylpropanoid that contributes to flower and ripe fruit scent. In ripe strawberry (Fragaria × ananassa) fruit receptacles, eugenol is biosynthesized by eugenol synthase (FaEGS2). However, the transcriptional regulation of this process is still unknown. We have identified and functionally characterized an R2R3 MYB transcription factor (emission of benzenoid II [FaEOBII]) that seems to be the orthologous gene of PhEOBII from Petunia hybrida, which contributes to the regulation of eugenol biosynthesis in petals. The expression of FaEOBII was ripening related and fruit receptacle specific, although high expression values were also found in petals. This expression pattern of FaEOBII correlated with eugenol content in both fruit receptacle and petals. The expression of FaEOBII was repressed by auxins and activated by abscisic acid, in parallel to the ripening process. In ripe strawberry receptacles, where the expression of FaEOBII was silenced, the expression of cinnamyl alcohol dehydrogenase1 and FaEGS2, two structural genes involved in eugenol production, was down-regulated. A subsequent decrease in eugenol content in ripe receptacles was also observed, confirming the involvement of FaEOBII in eugenol metabolism. Additionally, the expression of FaEOBII was under the control of FaMYB10, another R2R3 MYB transcription factor that regulates the early and late biosynthetic genes from the flavonoid/phenylpropanoid pathway. In parallel, the amount of eugenol in FaMYB10-silenced receptacles was also diminished. Taken together, these data indicate that FaEOBII plays a regulating role in the volatile phenylpropanoid pathway gene expression that gives rise to eugenol production in ripe strawberry receptacles.

  2. A flexible R package for nonnegative matrix factorization

    Directory of Open Access Journals (Sweden)

    Seoighe Cathal

    2010-07-01

    Full Text Available Abstract Background Nonnegative Matrix Factorization (NMF is an unsupervised learning technique that has been applied successfully in several fields, including signal processing, face recognition and text mining. Recent applications of NMF in bioinformatics have demonstrated its ability to extract meaningful information from high-dimensional data such as gene expression microarrays. Developments in NMF theory and applications have resulted in a variety of algorithms and methods. However, most NMF implementations have been on commercial platforms, while those that are freely available typically require programming skills. This limits their use by the wider research community. Results Our objective is to provide the bioinformatics community with an open-source, easy-to-use and unified interface to standard NMF algorithms, as well as with a simple framework to help implement and test new NMF methods. For that purpose, we have developed a package for the R/BioConductor platform. The package ports public code to R, and is structured to enable users to easily modify and/or add algorithms. It includes a number of published NMF algorithms and initialization methods and facilitates the combination of these to produce new NMF strategies. Commonly used benchmark data and visualization methods are provided to help in the comparison and interpretation of the results. Conclusions The NMF package helps realize the potential of Nonnegative Matrix Factorization, especially in bioinformatics, providing easy access to methods that have already yielded new insights in many applications. Documentation, source code and sample data are available from CRAN.

  3. An R2R3-MYB transcription factor regulates carotenoid pigmentation in Mimulus lewisii flowers.

    Science.gov (United States)

    Sagawa, Janelle M; Stanley, Lauren E; LaFountain, Amy M; Frank, Harry A; Liu, Chang; Yuan, Yao-Wu

    2016-02-01

    Carotenoids are yellow, orange, and red pigments that contribute to the beautiful colors and nutritive value of many flowers and fruits. The structural genes in the highly conserved carotenoid biosynthetic pathway have been well characterized in multiple plant systems, but little is known about the transcription factors that control the expression of these structural genes. By analyzing a chemically induced mutant of Mimulus lewisii through bulk segregant analysis and transgenic experiments, we have identified an R2R3-MYB, Reduced Carotenoid Pigmentation 1 (RCP1), as the first transcription factor that positively regulates carotenoid biosynthesis during flower development. Loss-of-function mutations in RCP1 lead to down-regulation of all carotenoid biosynthetic genes and reduced carotenoid content in M. lewisii flowers, a phenotype recapitulated by RNA interference in the wild-type background. Overexpression of this gene in the rcp1 mutant background restores carotenoid production and, unexpectedly, results in simultaneous decrease of anthocyanin production in some transgenic lines by down-regulating the expression of an activator of anthocyanin biosynthesis. Identification of transcriptional regulators of carotenoid biosynthesis provides the 'toolbox' genes for understanding the molecular basis of flower color diversification in nature and for potential enhancement of carotenoid production in crop plants via genetic engineering. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  4. Characterization of a citrus R2R3-MYB transcription factor that regulates the flavonol and hydroxycinnamic acid biosynthesis

    Science.gov (United States)

    Flavonols and hydroxycinnamic acids are important phenylpropanoid metabolites in plants. In this study, we isolated and characterized a citrus R2R3-MYB transcription factor CsMYBF1, encoding a protein belonging to the flavonol-specific MYB subgroup. Ectopic expression of CsMYBF1 in tomato led to an ...

  5. An R2R3 MYB transcription factor associated with regulation of the anthocyanin biosynthetic pathway in Rosaceae (on linr)

    NARCIS (Netherlands)

    Wang, Kui-Lin; Bolitho, Karen; Grafton, Karryn; Kortstee, A.J.; Karunairetnam, Sakuntala; McGhie, T.K.; Espley, R.V.; Hellens, R.P.; Allan, A.C.

    2010-01-01

    Background - The control of plant anthocyanin accumulation is via transcriptional regulation of the genes encoding the biosynthetic enzymes. A key activator appears to be an R2R3 MYB transcription factor. In apple fruit, skin anthocyanin levels are controlled by a gene called MYBA or MYB1, while the

  6. M148R and M149R are two virulence factors for myxoma virus pathogenesis in the European rabbit.

    Science.gov (United States)

    Blanié, Sophie; Mortier, Jérémy; Delverdier, Maxence; Bertagnoli, Stéphane; Camus-Bouclainville, Christelle

    2009-01-01

    Myxoma virus (MYXV), a member of the Poxviridae family, is the agent responsible for myxomatosis, a fatal disease in the European rabbit (Oryctolagus cuniculus). MYXV has a linear double-stranded DNA genome that encodes several factors important for evasion from the host immune system. Among them, four ankyrin (ANK) repeat proteins were identified: M148R, M149R, M150R and M-T5. To date, only M150R and M-T5 were studied and characterized as critical virulence factors. This article presents the first characterization of M148R and M149R. Green Fluorescent Protein (GFP) fusions allowed us to localize them in a viral context. Whereas M149R is only cytoplasmic, interestingly, M148R is in part located in the nucleolus, a unique feature for an ANK repeat poxviral protein. In order to evaluate their implication in viral pathogenicity, targeted M148R, M149R, or both deletions were constructed in the wild type T1 strain of myxoma virus. In vitro infection of rabbit and primate cultured cells as well as primary rabbit cells allowed us to conclude that M148R and M149R are not likely to be implicated in cell tropism or host range functions. However, in vivo experiments revealed that they are virulence factors since after infection of European rabbits with mutant viruses, a delay in the onset of clinical signs, an increase of survival time and a dramatic decrease in mortality rate were observed. Moreover, histological analysis suggests that M148R plays a role in the subversion of host inflammatory response by MYXV.

  7. Unexplained factors and their effects on second pass R-squared’s

    NARCIS (Netherlands)

    Kleibergen, F.; Zhan, Z.

    2015-01-01

    We construct the large sample distributions of the OLS and GLS R2R2’s of the second pass regression of the Fama and MacBeth (1973) two pass procedure when the observed proxy factors are minorly correlated with the true unobserved factors. This implies an unexplained factor structure in the first pas

  8. Venous thrombosis with both heterozygous factor V Leiden (R507Q) and factor II (G20210A) mutations.

    Science.gov (United States)

    Bhaijee, Feriyl; Jordan, Brenda; Pepper, Dominique J; Leacock, Rodney; Rock, William A

    2012-01-01

    Both hereditary and acquired factors increase the risk of venous thromboembolism, thus the clinical management of affected patients involves evaluation of genetic factors that predispose to hypercoagulability. Factor V Leiden (R507Q) and factor II (prothrombin) mutation (G20210A) are the two most common inherited hypercoagulability disorders among populations of European origin. Both factor V Leiden and factor II mutation (G20210A) represent gain-of-function mutations: factor V Leiden causes resistance to activated protein C, and factor II mutation (G20210A) results in higher levels of plasma prothrombin. Herein, we present an uncommon case of combined factor V Leiden mutation (R507Q) and factor II mutation (G20210A), and discuss the prevalence and features of each entity, as well as their role in the clinical management of affected patients.

  9. Factors Determining the Mode of Overseas R&D by Multinationals: Empirical Evidence

    OpenAIRE

    Ito, Banri; Wakasugi, Ryuhei

    2007-01-01

    The large expansion of MNCs' overseas R&D is noteworthy. This paper investigates the factors affecting the expansion of support-oriented R&D and knowledge sourcing R&D by using qualitative data which indicate the modes of R&D conducted at a plant site and a laboratory. The empirical results suggest that (1) the export propensity of affiliate firms, relative abundance of human resources for R&D, and accumulated technological knowledge have a positive effect on both the modes of R&D at a plant ...

  10. MiR-125a TNF receptor-associated factor 6 to inhibit osteoclastogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Li-Juan; Liao, Lan [Department of Endocrinology, Xiangya Hospital of Central South University, 87 Xiangya Road, Changsha, Hunan 410008 (China); Yang, Li [Department of Endocrinology, Hunan Province Geriatric Hospital, Changsha, Hunan 410001 (China); Li, Yu [Department of Endocrinology, Xiangya Hospital of Central South University, 87 Xiangya Road, Changsha, Hunan 410008 (China); Jiang, Tie-Jian, E-mail: jiangtiejian@gmail.com [Department of Endocrinology, Xiangya Hospital of Central South University, 87 Xiangya Road, Changsha, Hunan 410008 (China)

    2014-02-15

    MicroRNAs (miRNAs) play important roles in osteoclastogenesis and bone resorption. In the present study, we found that miR-125a was dramatically down-regulated during macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) induced osteoclastogenesis of circulating CD14+ peripheral blood mononuclear cells (PBMCs). Overexpression of miR-125a in CD14+ PBMCs inhibited osteoclastogenesis, while inhibition of miR-125a promoted osteoclastogenesis. TNF receptor-associated factor 6 (TRAF6), a transduction factor for RANKL/RANK/NFATc1 signal, was confirmed to be a target of miR-125a. EMSA and ChIP assays confirmed that NFATc1 bound to the promoter of the miR-125a. Overexpression of NFATc1 inhibited miR-125a transcription, and block of NFATc1 expression attenuated RANKL-regulated miR-125a transcription. Here, we reported that miR-125a played a biological function in osteoclastogenesis through a novel TRAF6/ NFATc1/miR-125a regulatory feedback loop. It suggests that regulation of miR-125a expression may be a potential strategy for ameliorating metabolic disease. - Highlights: • MiR-125a was significantly down-regulated in osteoclastogenesis of CD14+ PBMCs. • MiR-125a inhibited osteoclast differentiation by targeting TRAF6. • NFATc1 inhibited miR-125a transciption by binding to the promoter of miR-125a. • TRAF6/NFATc1 and miR-125a form a regulatory feedback loop in osteoclastogenesis.

  11. Role of Stress Factors on the Adhesion of Interfaces in R2R Fabricated Organic Photovoltaics

    DEFF Research Database (Denmark)

    Corazza, Michael; Rolston, Nicholas; Dauskardt, Reinhold H.

    2016-01-01

    The role of the common stress factors such as high temperature, humidity,and UV irradiation on interface adhesion of roll-to-roll fabricated organic photovoltaic (OPV) devices is investigated. The samples range from bare front electrodes to complete devices. It is shown that applying single stres...

  12. Unexplained factors and their effects on second pass R-squared's and t-tests

    NARCIS (Netherlands)

    Kleibergen, F.; Zhan, Z.

    2013-01-01

    We construct the large sample distributions of the OLS and GLS R2’s of the second pass regression of the Fama-MacBeth (1973) two pass procedure when the observed proxy factors are minorly correlated with the true unobserved factors. The small correlation implies a sizeable unexplained factor structu

  13. Mutual induction of transcription factor PPARγ and microRNAs miR-145 and miR-329.

    Science.gov (United States)

    Dharap, Ashutosh; Pokrzywa, Courtney; Murali, Shruthi; Kaimal, Balarama; Vemuganti, Raghu

    2015-10-01

    MicroRNAs (miRNAs) are small non-coding RNAs that are known to control mRNA translation. Most miRNAs are transcribed from specific genes with well-defined promoters located throughout the genome. The mechanisms that control miRNA expression under normal and pathological conditions are not yet understood clearly. Peroxisome proliferator-activated receptor (PPAR) γ is a ligand-activated transcription factor that is extensively distributed in the CNS. PPARγ activation induces neuroprotection by modulating genes that contain peroxisome proliferator response elements (PPREs) in their promoters. We presently evaluated if PPARγ modulates miRNA expression. When adult rats were treated with PPARγ agonist rosiglitazone, expression of 28 miRNAs altered significantly (12 up- and 16 down-regulated; 3-119 fold) in the cerebral cortex compared to vehicle-treated controls. In silico analysis showed 1-5 PPREs in the putative promoter regions (within 1 Kb upstream of the transcription start site) of these miRNA genes. Cotransfection with a PPARγ constitutively expressing vector significantly induced the miR-145 and miR-329 promoter vectors (each have four PPREs), which was curtailed by point mutations of PPREs in their promoters. Interestingly, the PPARγ promoter has binding sites for both these miRNAs and transfection with miR-329 mimic and miR-145 mimic induced the PPARγ expression. Thus, these studies show a cyclical induction of miRNAs and PPARγ, indicating that the pleiotropic beneficial effects of PPARγ agonists might be modulated in part by miRNAs and their down-stream mRNAs. We proposed that promoters of many microRNAs contain the binding sites for the transcription factor PPARγ. Activation of PPARγ modulates the expression of these microRNAs. Two such PPARγ-responsive microRNAs (miR-145 and miR-329) bind to PPARγ promoter to induce its expression. This indicates the presence of a feedback loop by which transcription factors and microRNAs can modulate each other.

  14. Genome-wide analysis of the R2R3-MYB transcription factor gene family in sweet orange (Citrus sinensis).

    Science.gov (United States)

    Liu, Chaoyang; Wang, Xia; Xu, Yuantao; Deng, Xiuxin; Xu, Qiang

    2014-10-01

    MYB transcription factor represents one of the largest gene families in plant genomes. Sweet orange (Citrus sinensis) is one of the most important fruit crops worldwide, and recently the genome has been sequenced. This provides an opportunity to investigate the organization and evolutionary characteristics of sweet orange MYB genes from whole genome view. In the present study, we identified 100 R2R3-MYB genes in the sweet orange genome. A comprehensive analysis of this gene family was performed, including the phylogeny, gene structure, chromosomal localization and expression pattern analyses. The 100 genes were divided into 29 subfamilies based on the sequence similarity and phylogeny, and the classification was also well supported by the highly conserved exon/intron structures and motif composition. The phylogenomic comparison of MYB gene family among sweet orange and related plant species, Arabidopsis, cacao and papaya suggested the existence of functional divergence during evolution. Expression profiling indicated that sweet orange R2R3-MYB genes exhibited distinct temporal and spatial expression patterns. Our analysis suggested that the sweet orange MYB genes may play important roles in different plant biological processes, some of which may be potentially involved in citrus fruit quality. These results will be useful for future functional analysis of the MYB gene family in sweet orange.

  15. The human factors of quality and QA in R D environments

    Energy Technology Data Exchange (ETDEWEB)

    Hill, S.G.

    1990-01-01

    Achieving quality is a human activity. It is therefore important to consider the human in the design, development and evaluation of work processes and environments in an effort to enhance human performance and minimize error. It is also important to allow for individual differences when considering human factors issues. Human Factors is the field of study which can provide information on integrating the human into the system. Human factors and quality are related for the customer of R D work, R D personnel who perform the work, and the quality professional who overviews the process of quality in the work. 18 refs., 1 fig.

  16. Spalt transcription factors are required for R3/R4 specification and establishment of planar cell polarity in the Drosophila eye.

    Science.gov (United States)

    Domingos, Pedro M; Mlodzik, Marek; Mendes, César S; Brown, Samara; Steller, Hermann; Mollereau, Bertrand

    2004-11-01

    The establishment of planar cell polarity in the Drosophila eye requires correct specification of the R3/R4 pair of photoreceptor cells. In response to a polarizing factor, Frizzled signaling specifies R3 and induces Delta, which activates Notch in the neighboring cell, specifying it as R4. Here, we show that the spalt zinc-finger transcription factors (spalt major and spalt-related) are part of the molecular mechanisms regulating R3/R4 specification and planar cell polarity establishment. In mosaic analysis, we find that the spalt genes are specifically required in R3 for the establishment of correct ommatidial polarity. In addition, we show that spalt genes are required for proper localization of Flamingo in the equatorial side of R3 and R4, and for the upregulation of Delta in R3. These requirements are very similar to those of frizzled during R3/R4 specification. We show that spalt genes are required cell-autonomously for the expression of seven-up in R3 and R4, and that seven-up is downstream of spalt genes in the genetic hierarchy of R3/R4 specification. Thus, spalt and seven-up are necessary for the correct interpretation of the Frizzled-mediated polarity signal in R3. Finally, we show that, posterior to row seven, seven-up represses spalt in R3/R4 in order to maintain the R3/R4 identity and to inhibit the transformation of these cells to the R7 cell fate.

  17. MiR-32 promotes gastric carcinoma tumorigenesis by targeting Kruppel-like factor 4

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Chao [Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730 (China); Yu, Jianchun, E-mail: yu_jchpumch@163.com [Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730 (China); Liu, Yuqin [Cell Culture Center, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005 (China); Kang, Weiming; Ma, Zhiqiang; Zhou, Li [Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730 (China)

    2015-11-27

    Gastric cancer (GC) is a prevalent malignant cancer worldwide and is highly lethal because of its fast growth. Currently, the clinical therapy options for GC remain limited. MiR-32 has been reported as an oncogenic microRNA in many cancers, but its role in GC is unclear. Here, we found that miR-32 was overexpressed in GC tissues compared with adjacent normal tissue, and miR-32 was higher in GC patients' plasma compared with healthy individuals. Furthermore, we have identified miR-32 to be oncogenic, by promoting gastric cell proliferation, migration and invasion. We also identified Kruppel-like factor 4 (KLF4) as a direct target of miR-32. Knockdown of KLF4 promoted proliferation, migration and invasion of GC cells. We conclude that miR-32 promotes GC cell proliferation, migration and invasion by targeting KLF4, suggesting that the miR-32-KLF4 pathway may be useful in clinical diagnosis and therapeutics. - Highlights: • miR-32 was overexpression in GC tissues than adjacent normal tissue. • miR-32 was higher in GC patients' plasma compared with healthy people. • miR-32 promotes GC cell proliferation, migration and invasion by targeting KLF4.

  18. OpaR controls a network of downstream transcription factors in Vibrio parahaemolyticus BB22OP.

    Directory of Open Access Journals (Sweden)

    Alison Kernell Burke

    Full Text Available Vibrio parahaemolyticus is an emerging world-wide human pathogen that is associated with food-borne gastroenteritis when raw or undercooked seafood is consumed. Expression of virulence factors in this organism is modulated by the phenomenon known as quorum sensing, which permits differential gene regulation at low versus high cell density. The master regulator of quorum sensing in V. parahaemolyticus is OpaR. OpaR not only controls virulence factor gene expression, but also the colony and cellular morphology associated with growth on a surface and biofilm formation. Whole transcriptome Next Generation sequencing (RNA-Seq was utilized to determine the OpaR regulon by comparing strains BB22OP (opaR+, LM5312 and BB22TR (∆opaR1, LM5674. This work, using the published V. parahaemolyticus BB22OP genome sequence, confirms and expands upon a previous microarray analysis for these two strains that used an Affymetrix GeneChip designed from the closely related V. parahaemolyticus RIMD2210633 genome sequence. Overall there was excellent correlation between the microarray and RNA-Seq data. Eleven transcription factors under OpaR control were identified by both methods and further confirmed by quantitative reverse transcription PCR (qRT-PCR analysis. Nine of these transcription factors were demonstrated to be direct OpaR targets via in vitro electrophoretic mobility shift assays with purified hexahistidine-tagged OpaR. Identification of the direct and indirect targets of OpaR, including small RNAs, will enable the construction of a network map of regulatory interactions important for the switch between the nonpathogenic and pathogenic states.

  19. rNAPc2 inhibits colorectal cancer in mice through tissue factor.

    Science.gov (United States)

    Zhao, Jingsong; Aguilar, Gerard; Palencia, Servando; Newton, Elizabeth; Abo, Arie

    2009-01-01

    Recombinant nematode anticoagulant protein c2 (rNAPc2) is a specific inhibitor of tissue factor (TF)/factor VIIa complex with novel antithrombotic activity. TF is highly expressed in human colorectal tumors, and levels are positively correlated with disease progression. To explore the therapeutic potential and mechanism of action of rNAPc2 during tumor growth and metastasis, we tested rNAPc2 in several experimental colorectal cancer models in mice. Administration of rNAPc2 inhibited pulmonary metastasis in mice systemically disseminated with CT26 murine colon carcinoma cells in a dose-dependent fashion. Combining rNAPc2 with the cytotoxic agent 5-fluorouracil or bevacizumab (humanized anti-vascular endothelial growth factor monoclonal antibody) resulted in additive growth inhibition and simultaneous reduction of microvessel density in HCT116 human colorectal tumor xenografts in nude mice. Furthermore, rNAPc2 potentiated CPT-11 in inhibiting hepatic metastasis in nude mice with portal vein injection of HCT116 tumor cells. Long-term administration of rNAPc2 significantly suppressed spontaneous formation of intestinal tumors in Apc(Min/+) mice. Using a RNA interference approach, we showed that TF expression is necessary for rNAPc2-mediated inhibition of HCT116 human colorectal tumor xenograft growth in nude mice, indicating that the antitumor effect of rNAPc2 may be transduced through TF that is expressed on tumor cells. rNAPc2 is a potent anticancer agent when used in combination with chemotherapy or antiangiogenic therapy in mouse models of colorectal cancer, and TF positivity appears to be required for its activity.

  20. The LysR-type transcription factor PacR is a global regulator of photosynthetic carbon assimilation in Anabaena.

    Science.gov (United States)

    Picossi, Silvia; Flores, Enrique; Herrero, Antonia

    2015-09-01

    Cyanobacteria perform water-splitting photosynthesis and are important primary producers impacting the carbon and nitrogen cycles at global scale. They fix CO2 through ribulose-bisphosphate carboxylase/oxygenase (RuBisCo) and have evolved a distinct CO2 concentrating mechanism (CCM) that builds high CO2 concentrations in the vicinity of RuBisCo favouring its carboxylase activity. Filamentous cyanobacteria such as Anabaena fix CO2 in photosynthetic vegetative cells, which donate photosynthate to heterocysts that rely on a heterotrophic metabolism to fix N2 . CCM elements are induced in response to inorganic carbon limitation, a cue that exposes the photosynthetic apparatus to photodamage by over-reduction. An Anabaena mutant lacking the LysR-type transcription factor All3953 grew poorly and dies under high light. The rbcL operon encoding RuBisCo was induced upon carbon limitation in the wild type but not in the mutant. ChIP-Seq analysis was used to globally identify All3953 targets under carbon limitation. Targets include, besides rbcL, genes encoding CCM elements, photorespiratory pathway- photosystem- and electron transport-related components, and factors, including flavodiiron proteins, with a demonstrated or putative function in photoprotection. Quantitative reverse transcription polymerase chain reaction analysis of selected All3953 targets showed regulation in the wild type but not in the mutant. All3953 (PacR) is a global regulator of carbon assimilation in an oxygenic photoautotroph.

  1. Interactions between the R2R3-MYB transcription factor, AtMYB61, and target DNA binding sites.

    Directory of Open Access Journals (Sweden)

    Michael B Prouse

    Full Text Available Despite the prominent roles played by R2R3-MYB transcription factors in the regulation of plant gene expression, little is known about the details of how these proteins interact with their DNA targets. For example, while Arabidopsis thaliana R2R3-MYB protein AtMYB61 is known to alter transcript abundance of a specific set of target genes, little is known about the specific DNA sequences to which AtMYB61 binds. To address this gap in knowledge, DNA sequences bound by AtMYB61 were identified using cyclic amplification and selection of targets (CASTing. The DNA targets identified using this approach corresponded to AC elements, sequences enriched in adenosine and cytosine nucleotides. The preferred target sequence that bound with the greatest affinity to AtMYB61 recombinant protein was ACCTAC, the AC-I element. Mutational analyses based on the AC-I element showed that ACC nucleotides in the AC-I element served as the core recognition motif, critical for AtMYB61 binding. Molecular modelling predicted interactions between AtMYB61 amino acid residues and corresponding nucleotides in the DNA targets. The affinity between AtMYB61 and specific target DNA sequences did not correlate with AtMYB61-driven transcriptional activation with each of the target sequences. CASTing-selected motifs were found in the regulatory regions of genes previously shown to be regulated by AtMYB61. Taken together, these findings are consistent with the hypothesis that AtMYB61 regulates transcription from specific cis-acting AC elements in vivo. The results shed light on the specifics of DNA binding by an important family of plant-specific transcriptional regulators.

  2. What Factors Underlie the Aging Effects on WAIS-R and WAIS-III Subtests?

    Science.gov (United States)

    Gregoire, Jacques

    2001-01-01

    Studied the factors underlying the aging effects seen on the Wechsler Intelligence Scale for Adults-Revised (WAIS-R) and the scale's third edition (WAIS-III) using the French standardization samples of 1,104 for the WAIS-III and 1,000 for the WAIS-R. Results show that the observed decline in scores for both tests cannot be fully explained with a…

  3. The WAIS-R factors: usefulness and construct validity in neuropsychological assessments.

    Science.gov (United States)

    Berger, S

    1998-01-01

    One-hundred and twelve patients were administered the Wechsler Adult Intelligence Scale-Revised (WAIS-R), an abbreviated Wechsler Memory Scale-Revised, and the Halstead-Reitan Neuropsychological Test Battery. In order to replicate an earlier study (Sherman, Strauss, Spellacy, & Hunter, 1995), correlations were generated between the WAIS-R factor scores and neuropsychological and memory tests. The Verbal Comprehension factor (Factor 1) correlated with Speech Sounds Perception Test (SSPT), the Seashore Rhythm Test (SSRT), the Category Test, and memory indices. The Perceptual Organizational factor (Factor 2) correlated with the time, memory, and location scores of the Tactual Performance Test, the SSPT, SSRT, the Category Test, Trails A, Trails B, memory indices, and finger tapping. The Freedom From Distractibility factor (Factor 3) was correlated with the Category Test, the SSPT, the SSRT, Trails A, Trails B, immediate Logical Memory, and Visual Reproduction. Modest correlations suggest that the WAIS-R factors may be useful for understanding underlying cognitive performance and can be functional for generating hypotheses, but should not be utilized exclusively to make clinical inferences.

  4. An R2R3 MYB transcription factor determines red petal colour in an Actinidia (kiwifruit) hybrid population.

    Science.gov (United States)

    Fraser, Lena G; Seal, Alan G; Montefiori, Mirco; McGhie, Tony K; Tsang, Gianna K; Datson, Paul M; Hilario, Elena; Marsh, Hinga E; Dunn, Juanita K; Hellens, Roger P; Davies, Kevin M; McNeilage, Mark A; De Silva, H Nihal; Allan, Andrew C

    2013-01-16

    Red colour in kiwifruit results from the presence of anthocyanin pigments. Their expression, however, is complex, and varies among genotypes, species, tissues and environments. An understanding of the biosynthesis, physiology and genetics of the anthocyanins involved, and the control of their expression in different tissues, is required. A complex, the MBW complex, consisting of R2R3-MYB and bHLH transcription factors together with a WD-repeat protein, activates anthocyanin 3-O-galactosyltransferase (F3GT1) to produce anthocyanins. We examined the expression and genetic control of anthocyanins in flowers of Actinidia hybrid families segregating for red and white petal colour. Four inter-related backcross families between Actinidia chinensis Planch. var. chinensis and Actinidia eriantha Benth. were identified that segregated 1:1 for red or white petal colour. Flower pigments consisted of five known anthocyanins (two delphinidin-based and three cyanidin-based) and three unknowns. Intensity and hue differed in red petals from pale pink to deep magenta, and while intensity of colour increased with total concentration of anthocyanin, no association was found between any particular anthocyanin data and hue. Real time qPCR demonstrated that an R2R3 MYB, MYB110a, was expressed at significant levels in red-petalled progeny, but not in individuals with white petals.A microsatellite marker was developed that identified alleles that segregated with red petal colour, but not with ovary, stamen filament, or fruit flesh colour in these families. The marker mapped to chromosome 10 in Actinidia.The white petal phenotype was complemented by syringing Agrobacterium tumefaciens carrying Actinidia 35S::MYB110a into the petal tissue. Red pigments developed in white petals both with, and without, co-transformation with Actinidia bHLH partners. MYB110a was shown to directly activate Actinidia F3GT1 in transient assays. The transcription factor, MYB110a, regulates anthocyanin production in

  5. Direct regulation of rRNA transcription by fibroblast growth factor 2.

    Science.gov (United States)

    Sheng, Zhi; Liang, Yanping; Lin, Chih-Yin; Comai, Lucio; Chirico, William J

    2005-11-01

    Fibroblast growth factor 2 (FGF-2), which is highly expressed in developing tissues and malignant cells, regulates cell growth, differentiation, and migration. Five isoforms (18 to approximately 34 kDa) of FGF-2 are derived from alternative initiation codons of a single mRNA. The 18-kDa FGF-2 isoform is released from cells by a nonclassical secretory pathway and regulates gene expression by binding to cell surface receptors. This isoform also localizes to the nucleolus, raising the possibility that it may directly regulate ribosome biogenesis, a rate-limiting process in cell growth. Although several growth factors have been shown to accumulate in the nucleolus, their function and mechanism of action remain unclear. Here we show that 18-kDa FGF-2 interacts with upstream binding factor (UBF), an architectural transcription factor essential for rRNA transcription. The maximal activation of rRNA transcription in vitro by 18-kDa FGF-2 requires UBF. The 18-kDa FGF-2 localizes to rRNA genes and is necessary for the full activation of pre-rRNA synthesis in vivo. Our results demonstrate that 18-kDa FGF-2 directly regulates rRNA transcription.

  6. Coagulation factor VII, serum-triglycerides and the R/Q353 polymorphism: Differences between older men and women

    NARCIS (Netherlands)

    Mennen, L.I.; Maat, M.P.M. de; Schouten, E.G.; Kluft, C.; Jong, P.T.V.M. de; Hofman, A.; Grobbee, D.E.

    1997-01-01

    Coagulation factor VII activity (FVII:C) is a risk indicator for cardiovascular disease. It is related to serum-triglycerides and the R/Q353 polymorphism (alleles R and Q) in the gene coding for factor VII is strongly associated with factor VU[. The association of serum-triglycerides with factor VII

  7. Coagulation factor VII, serum-triglycerides and the R/Q353 polymorphism: Differences between older men and women

    NARCIS (Netherlands)

    Mennen, L.I.; Maat, M.P.M. de; Schouten, E.G.; Kluft, C.; Jong, P.T.V.M. de; Hofman, A.; Grobbee, D.E.

    1997-01-01

    Coagulation factor VII activity (FVII:C) is a risk indicator for cardiovascular disease. It is related to serum-triglycerides and the R/Q353 polymorphism (alleles R and Q) in the gene coding for factor VII is strongly associated with factor VU[. The association of serum-triglycerides with factor VII

  8. MYB56 Encoding a R2R3 MYB Transcription Factor Regulates Seed Size in Arabidopsis thaliana

    Institute of Scientific and Technical Information of China (English)

    Yanjie Zhang; Wanqi Liang; Jianxin Shi; Jie Xu; Dabing Zhang

    2013-01-01

    Plant seed size is tightly regulated by the development of seed coat, embryo, and endosperm;however, currently, its underlying mechanism remains unclear. In this study, we revealed a regulatory role of an R2R3 MYB transcription factor MYB56 in controlling seed size specifically in Arabidopsis thaliana L. Loss-of-function or knock-down of MYB56 yielded smaller seeds as compared with the wild type. Conversely, overexpression of MYB56 produced larger seeds. Further observation using semi-thin sections showed that myb56 developed smaller contracted endothelial cells and reduced cell number in the outer integument layer of the seed coat during the seed development;by contrast, MYB56 overexpressing lines had expanded endothelial cells and increased cell number in the outer integument layer of the seed coat, suggesting the essential role of MYB56 in regulating seed development. In addition, reciprocal cross-analysis showed that MYB56 affected the seed development maternally. MYB56 was shown to be dominantly expressed in developing seeds, consistently with its function in seed development. Moreover, quantitative reverse transcription polymerase chain reaction analysis revealed that MYB56 regulates the expression of genes involved in cell wall metabolism such as cell division and expansion. Altogether, our results demonstrated that MYB56 represents an unknown pathway for positively controlling the seed size.

  9. MULTIPASS, a rice R2R3-type MYB transcription factor, regulates adaptive growth by integrating multiple hormonal pathways.

    Science.gov (United States)

    Schmidt, Romy; Schippers, Jos H M; Mieulet, Delphine; Obata, Toshihiro; Fernie, Alisdair R; Guiderdoni, Emmanuel; Mueller-Roeber, Bernd

    2013-10-01

    Growth regulation is an important aspect of plant adaptation during environmental perturbations. Here, the role of MULTIPASS (OsMPS), an R2R3-type MYB transcription factor of rice, was explored. OsMPS is induced by salt stress and expressed in vegetative and reproductive tissues. Over-expression of OsMPS reduces growth under non-stress conditions, while knockdown plants display increased biomass. OsMPS expression is induced by abscisic acid and cytokinin, but is repressed by auxin, gibberellin and brassinolide. Growth retardation caused by OsMPS over-expression is partially restored by auxin application. Expression profiling revealed that OsMPS negatively regulates the expression of EXPANSIN (EXP) and cell-wall biosynthesis as well as phytohormone signaling genes. Furthermore, the expression of OsMPS-dependent genes is regulated by auxin, cytokinin and abscisic acid. Moreover, we show that OsMPS is a direct upstream regulator of OsEXPA4, OsEXPA8, OsEXPB2, OsEXPB3, OsEXPB6 and the endoglucanase genes OsGLU5 and OsGLU14. The multiple responses of OsMPS and its target genes to various hormones suggest an integrative function of OsMPS in the cross-talk between phytohormones and the environment to regulate adaptive growth.

  10. R7 Photoreceptor Specification in the Developing Drosophila Eye: The Role of the Transcription Factor Deadpan.

    Directory of Open Access Journals (Sweden)

    Yannis Emmanuel Mavromatakis

    2016-07-01

    Full Text Available As cells proceed along their developmental pathways they make a series of sequential cell fate decisions. Each of those decisions needs to be made in a robust manner so there is no ambiguity in the state of the cell as it proceeds to the next stage. Here we examine the decision made by the Drosophila R7 precursor cell to become a photoreceptor and ask how the robustness of that decision is achieved. The transcription factor Tramtrack (Ttk inhibits photoreceptor assignment, and previous studies found that the RTK-induced degradation of Ttk was critically required for R7 specification. Here we find that the transcription factor Deadpan (Dpn is also required; it is needed to silence ttk transcription, and only when Ttk protein degradation and transcriptional silencing occur together is the photoreceptor fate robustly achieved. Dpn expression needs to be tightly restricted to R7 precursors, and we describe the role played by Ttk in repressing dpn transcription. Thus, Dpn and Ttk act as mutually repressive transcription factors, with Dpn acting to ensure that Ttk is effectively removed from R7, and Ttk acting to prevent Dpn expression in other cells. Furthermore, we find that N activity is required to promote dpn transcription, and only in R7 precursors does the removal of Ttk coincide with high N activity, and only in this cell does Dpn expression result.

  11. Transcription-coupled nucleotide excision repair factors promote R-loop-induced genome instability.

    Science.gov (United States)

    Sollier, Julie; Stork, Caroline Townsend; García-Rubio, María L; Paulsen, Renee D; Aguilera, Andrés; Cimprich, Karlene A

    2014-12-18

    R-loops, consisting of an RNA-DNA hybrid and displaced single-stranded DNA, are physiological structures that regulate various cellular processes occurring on chromatin. Intriguingly, changes in R-loop dynamics have also been associated with DNA damage accumulation and genome instability; however, the mechanisms underlying R-loop-induced DNA damage remain unknown. Here we demonstrate in human cells that R-loops induced by the absence of diverse RNA processing factors, including the RNA/DNA helicases Aquarius (AQR) and Senataxin (SETX), or by the inhibition of topoisomerase I, are actively processed into DNA double-strand breaks (DSBs) by the nucleotide excision repair endonucleases XPF and XPG. Surprisingly, DSB formation requires the transcription-coupled nucleotide excision repair (TC-NER) factor Cockayne syndrome group B (CSB), but not the global genome repair protein XPC. These findings reveal an unexpected and potentially deleterious role for TC-NER factors in driving R-loop-induced DNA damage and genome instability.

  12. Transcription-coupled nucleotide excision repair factors promote R-loop-induced genome instability

    Science.gov (United States)

    Sollier, Julie; Stork, Caroline Townsend; García-Rubio, María L.; Paulsen, Renee D.; Aguilera, Andrés; Cimprich, Karlene A.

    2014-01-01

    Summary R-loops, consisting of an RNA-DNA hybrid and displaced single-stranded DNA, are physiological structures that regulate various cellular processes occurring on chromatin. Intriguingly, changes in R-loop dynamics have also been associated with DNA damage accumulation and genome instability, however the mechanisms underlying R-loop induced DNA damage remain unknown. Here we demonstrate in human cells that R-loops induced by the absence of diverse RNA processing factors, including the RNA/DNA helicases Aquarius (AQR) and Senataxin (SETX), or by the inhibition of topoisomerase I, are actively processed into DNA double-strand breaks (DSBs) by the nucleotide excision repair endonucleases XPF and XPG. Surprisingly, DSB formation requires the transcription-coupled nucleotide excision repair (TC-NER) factor Cockayne syndrome group B (CSB), but not the global genome repair protein XPC. These findings reveal an unexpected and potentially deleterious role for TC-NER factors in driving R-loop-induced DNA damage and genome instability. PMID:25435140

  13. Staphylococcus aureus SaeR/S-regulated factors reduce human neutrophil reactive oxygen species production.

    Science.gov (United States)

    Guerra, Fermin E; Addison, Conrad B; de Jong, Nienke W M; Azzolino, Joseph; Pallister, Kyler B; van Strijp, Jos A G; Voyich, Jovanka M

    2016-11-01

    Neutrophils are the first line of defense after a pathogen has breached the epithelial barriers, and unimpaired neutrophil functions are essential to clear infections. Staphylococcus aureus is a prevalent human pathogen that is able to withstand neutrophil killing, yet the mechanisms used by S. aureus to inhibit neutrophil clearance remain incompletely defined. The production of reactive oxygen species (ROS) is a vital neutrophil antimicrobial mechanism. Herein, we test the hypothesis that S. aureus uses the SaeR/S two-component gene regulatory system to produce virulence factors that reduce neutrophil ROS production. With the use of ROS probes, the temporal and overall production of neutrophil ROS was assessed during exposure to the clinically relevant S. aureus USA300 (strain LAC) and its isogenic mutant LACΔsaeR/S Our results demonstrated that SaeR/S-regulated factors do not inhibit neutrophil superoxide (O2(-)) production. However, subsequent neutrophil ROS production was significantly reduced during exposure to LAC compared with LACΔsaeR/S In addition, neutrophil H2O2 production was reduced significantly by SaeR/S-regulated factors by a mechanism independent of catalase. Consequently, the reduction in neutrophil H2O2 resulted in decreased production of the highly antimicrobial agent hypochlorous acid/hypochlorite anion (HOCl/(-)OCl). These findings suggest a new evasion strategy used by S. aureus to diminish a vital neutrophil antimicrobial mechanism. © Society for Leukocyte Biology.

  14. Alternative splicing of anciently exonized 5S rRNA regulates plant transcription factor TFIIIA.

    Science.gov (United States)

    Fu, Yan; Bannach, Oliver; Chen, Hao; Teune, Jan-Hendrik; Schmitz, Axel; Steger, Gerhard; Xiong, Liming; Barbazuk, W Brad

    2009-05-01

    Identifying conserved alternative splicing (AS) events among evolutionarily distant species can prioritize AS events for functional characterization and help uncover relevant cis- and trans-regulatory factors. A genome-wide search for conserved cassette exon AS events in higher plants revealed the exonization of 5S ribosomal RNA (5S rRNA) within the gene of its own transcription regulator, TFIIIA (transcription factor for polymerase III A). The 5S rRNA-derived exon in TFIIIA gene exists in all representative land plant species but not in green algae and nonplant species, suggesting it is specific to land plants. TFIIIA is essential for RNA polymerase III-based transcription of 5S rRNA in eukaryotes. Integrating comparative genomics and molecular biology revealed that the conserved cassette exon derived from 5S rRNA is coupled with nonsense-mediated mRNA decay. Utilizing multiple independent Arabidopsis overexpressing TFIIIA transgenic lines under osmotic and salt stress, strong accordance between phenotypic and molecular evidence reveals the biological relevance of AS of the exonized 5S rRNA in quantitative autoregulation of TFIIIA homeostasis. Most significantly, this study provides the first evidence of ancient exaptation of 5S rRNA in plants, suggesting a novel gene regulation model mediated by the AS of an anciently exonized noncoding element.

  15. Control of trichome formation in Arabidopsis by poplar single-repeat R3 MYB transcription factors

    Directory of Open Access Journals (Sweden)

    Limei eZhou

    2014-06-01

    Full Text Available In Arabidopsis, trichome formation is regulated by the interplay of R3 MYBs and several others transcription factors including the WD40-repeat protein TRANSPARENT TESTA GLABRA1 (TTG1, the R2R3 MYB transcription factor GLABRA1 (GL1, the bHLH transcription factor GLABRA3 (GL3 or ENHANCER OF GLABRA3 (EGL3, and the homeodomain protein GLABRA2 (GL2. R3 MYBs including TRICHOMELESS1 (TCL1, TRYPTICHON (TRY, CAPRICE (CPC, ENHANCER OF TRY AND CPC1 (ETC1, ETC2 and ETC3 negatively regulate trichome formation by competing with GL1 for binding GL3 or EGL3, thus blocking the formation of TTG1-GL3/EGL3-GL1, an activator complex required for the activation of the trichome positive regulator gene GL2. However, it is largely unknown if R3 MYBs in other plant species especially woody plants have similar functions. By BLASTing the Populus trichocarpa protein database using the entire amino acid sequence of TCL1, an Arabidopsis R3 MYB transcription factor, we identified a total of eight R3 MYB transcription factor genes in poplar, namely Populus trichocarpa TRICHOMELESS1through 8 (PtrTCL1-PtrTCL8. The amino acid signature required for interacting with bHLH transcription factors and the amino acids required for cell-to-cell movement of R3 MYBs are not fully conserved in all PtrTCLs. When tested in Arabidopsis protoplasts, however, all PtrTCL interacted with GL3. Expressing each of the eight PtrTCLs genes in Arabidopsis resulted in either glabrous phenotypes or plants with reduced trichome numbers, and expression levels of GL2 in all transgenic plants tested were greatly reduced. Expression of PtrTCL1 under the control of TCL1 native promoter almost completely complemented the mutant phenotype of tcl. In contrast, expression of PtrTCL1 under the control of TRY native promoter in the try mutant, or under the control of CPC native promoter in the cpc mutant resulted in glabrous phenotypes, suggesting that PtrTCL1 functions similarly to TCL1, but not TRY and CPC.

  16. Low socioeconomic status is a risk factor for preeclampsia: the Generation R Study.

    NARCIS (Netherlands)

    L.M. Silva (Lindsay); M. Coolman (Marianne); E.A.P. Steegers (Eric); V.W.V. Jaddoe (Vincent); H.A. Moll (Henriëtte); A. Hofman (Albert); J.P. Mackenbach (Johan); H. Raat (Hein)

    2008-01-01

    textabstractObjectives: To examine whether maternal socioeconomic status, as indicated by maternal educational level, is associated with preeclampsia, and if so, to what extent known risk factors for preeclampsia mediate the effect of educational level. Methods: In the Generation R Study, a populat

  17. An Evaluation of the Reliability, Construct Validity, and Factor Structure of the Static-2002R.

    Science.gov (United States)

    Jung, Sandy; Ennis, Liam; Hermann, Chantal A; Pham, Anna T; Choy, Alberto L; Corabian, Gabriela; Hook, Tarah

    2017-03-01

    The fundamental psychometric properties of the subscales found in the Static-2002R, an actuarial measure of sexual recidivism risk, were evaluated in the current study. Namely, the reliability, concurrent and construct validity, and factor structure of the Static-2002R subscales were examined with a sample of 372 adult male sex offenders. In addition to using validated measures of sexual violence risk to examine concurrent validity, construct-related measures taken from extant risk measures and psychometric tests were correlated with three of the subscales to assess overall construct validity. Moderate support was found for the reliability of the Static-2002R. The concurrent and construct validity of the General Criminality, Persistence of Sexual Offending, and Deviant Sexual Interest subscales were supported. Generally, these findings further support the Static-2002R as a valid sex offender risk appraisal instrument that encompasses multiple distinct, clinically relevant, risk domains.

  18. The M358R variant of α(1)-proteinase inhibitor inhibits coagulation factor VIIa.

    Science.gov (United States)

    Sheffield, William P; Bhakta, Varsha

    2016-02-12

    The naturally occurring M358R mutation of the plasma serpin α1-proteinase inhibitor (API) changes both its cleavable reactive centre bond to Arg-Ser and the efficacy with which it inhibits different proteases, reducing the rate of inhibition of neutrophil elastase, and enhancing that of thrombin, factor XIa, and kallikrein, by several orders of magnitude. Although another plasma serpin with an Arg-Ser reactive centre, antithrombin (AT), has been shown to inhibit factor VIIa (FVIIa), no published data are available with respect to FVIIa inhibition by API M358R. Recombinant bacterially-expressed API M358R and plasma-derived AT were therefore compared using gel-based and kinetic assays of FVIIa integrity and activity. Under pseudo-first order conditions of excess serpin over protease, both AT and API M358R formed denaturation-resistant inhibitory complexes with FVIIa in reactions accelerated by TF; AT, but not API M358R, also required heparin for maximal activity. The second order rate constant for heparin-independent API M358R-mediated FVIIa inhibition was determined to be 7.8 ± 0.8 × 10(2) M(-1)sec(-1). We conclude that API M358R inhibits FVIIa by forming inhibitory complexes of the serpin type more rapidly than AT in the absence of heparin. The likely 20-fold excess of API M358R over AT in patient plasma during inflammation raises the possibility that it could contribute to the hemorrhagic tendencies manifested by rare individuals expressing this mutant serpin.

  19. Molecular characterization of the Jatropha curcas JcR1MYB1 gene encoding a putative R1-MYB transcription factor

    Directory of Open Access Journals (Sweden)

    Hui-Liang Li

    2014-09-01

    Full Text Available The cDNA encoding the R1-MYB transcription factor, designated as JcR1MYB1, was isolated from Jatropha curcas using rapid amplification of cDNA ends. JcR1MYB1 contains a 951 bp open reading frame that encodes 316 amino acids. The deduced JcR1MYB1 protein was predicted to possess the conserved, 56-amino acid-long DNA-binding domain, which consists of a single helix-turn-helix module and usually occurs in R1-MYBs. JcR1MYB1 is a member of the R1-MYB transcription factor subfamily. A subcellular localization study confirmed the nuclear localization of JcR1MYB1. Expression analysis showed that JcR1MYB1 transcripts accumulated in various examined tissues, with high expression levels in the root and low levels in the stem. JcR1MYB1 transcription was up-regulated by polyethylene glycol, NaCl, and cold treatments, as well as by abscisic acid, jasmonic acid, and ethylene treatment. Analysis of transgenic tobacco plants over-expressing JcR1MYB1 indicates an inportant function for this gene in salt stress.

  20. Dietary effects on coagulation factor VII vary across genotypes of the R/Q353 polymorphism in elderly people

    NARCIS (Netherlands)

    Mennen, L.I.; Maat, M.P.M. de; Schouten, E.G.; Kluft, C.; Witteman, J.C.M.; Hofman, A.; Grobbee, D.E.

    1998-01-01

    The objective of this study was to evaluate the association of factor VII with dietary factors while also considering the R/Q353 polymorphism. Nutrition is an important determinant of coagulation factor VII, which is also genetically determined by the R/Q353 polymorphism. High levels of coagulation

  1. Construct Validity of WAIS-R Factors: Neuropsychological Test Correlates in Adults Referred for Evaluation of Possible Head Injury.

    Science.gov (United States)

    Sherman, Elisabeth M. S.; And Others

    1995-01-01

    A 3-factor solution of the Wechsler Adult Intelligence Scale--Revised (WAIS-R) in 260 adults with suspected head injury suggested relatively good construct validity for the factors, based on correlations with neuropsychological tests. Findings are discussed in terms of the multidimensional nature of neuropsychological tests and WAIS-R factors.…

  2. Global transcriptional profiling reveals Streptococcus agalactiae genes controlled by the MtaR transcription factor

    Directory of Open Access Journals (Sweden)

    Cvek Urska

    2008-12-01

    Full Text Available Abstract Background Streptococcus agalactiae (group B Streptococcus; GBS is a significant bacterial pathogen of neonates and an emerging pathogen of adults. Though transcriptional regulators are abundantly encoded on the GBS genome, their role in GBS pathogenesis is poorly understood. The mtaR gene encodes a putative LysR-type transcriptional regulator that is critical for the full virulence of GBS. Previous studies have shown that an mtaR- mutant transports methionine at reduced rates and grows poorly in normal human plasma not supplemented with methionine. The decreased virulence of the mtaR mutant was correlated with a methionine transport defect; however, no MtaR-regulated genes were identified. Results Microarray analysis of wild-type GBS and an mtaR mutant revealed differential expression of 12 genes, including 1 upregulated and 11 downregulated genes in the mtaR mutant. Among the downregulated genes, we identified a cluster of cotranscribed genes encoding a putative methionine transporter (metQ1NP and peptidase (pdsM. The expression of four genes potentially involved in arginine transport (artPQ and arginine biosynthesis (argGH was downregulated and these genes localized to two transcriptional units. The virulence factor cspA, which encodes an extracellular protease, was downregulated. Additionally, the SAN_1255 locus, which putatively encodes a protein displaying similarity to plasminogen activators, was downregulated. Conclusion To our knowledge, this is the first study to describe the global influence of MtaR on GBS gene expression. This study implicates the metQ1NP genes as encoding the MtaR-regulated methionine transporter, which may provide a mechanistic explanation for the methionine-dependent growth defect of the mtaR mutant. In addition to modulating the expression of genes involved in metabolism and amino acid transport, inactivation of mtaR affected the expression of other GBS genes implicated in pathogenesis. These findings

  3. Exploratory Factor Analysis of SCL90-R Symptoms Relevant to Psychosis

    Directory of Open Access Journals (Sweden)

    Javad Amini

    2011-10-01

    Full Text Available "nObjective: Inconsistent results have been reported regarding the symptom dimensions relevant to psychosis in symptoms check list revised (SCL90-R, i.e., "psychoticism" and "paranoid ideation". Therefore, some studies have suggested different factor structures for questions of these two dimensions, and proposed two newly defined dimensions of "schizotypal signs" and "schizophrenia nuclear symptoms". We conducted an exploratory factor analysis on the items of these two dimensions in a general population sample in Iran. "nMethod: A total of 2158 subjects residing in Southern Tehran (capital of Iran were interviewed using the psychoticism and paranoid ideation questions in SCL90-R to assess severity of these symptom dimensions. Factor analysis was done through SAS 9.1.3 PROC FACTOR using Promax rotation (power=3 on the matrix of "polychoric correlations among variables" as the input data. "nResults: Two factors were retained by the proportion criterion. Considering loadings >= 0.5 as minimum criteria for factor loadings, 7 out of 10 questions  from psychoticism ,and 3 out of 6 questions from paranoid ideation were retained, and others were eliminated. The factor labels proposed by the questionnaire suited the extracted factors and were retained. Internal consistency for each of the dimensions was acceptable (Cronbach's alpha 0.7 and 0.74 for paranoid ideation and psychoticism respectively. Composite scores showed a half-normal distribution for both dimensions which is predictable for instruments that detect psychotic symptoms. "nConclusion: Results were in contrast with similar studies, and questioned them by suggesting a different factor structure obtained from a statistically large population. The population in a developing nation (Iran in this study and the socio-cultural differences in developed settings are the potential sources for discrepancies between this analysis and previous reports.

  4. rVISTA for Comparative Sequence-Based Discovery of Functional Transcription Factor Binding Sites

    Energy Technology Data Exchange (ETDEWEB)

    Loots, Gabriela G.; Ovcharenko, Ivan; Pachter, Lior; Dubchak, Inna; Rubin, Edward M.

    2002-03-08

    Identifying transcriptional regulatory elements represents a significant challenge in annotating the genomes of higher vertebrates. We have developed a computational tool, rVISTA, for high-throughput discovery of cis-regulatory elements that combines transcription factor binding site prediction and the analysis of inter-species sequence conservation. Here, we illustrate the ability of rVISTA to identify true transcription factor binding sites through the analysis of AP-1 and NFAT binding sites in the 1 Mb well-annotated cytokine gene cluster1 (Hs5q31; Mm11). The exploitation of orthologous human-mouse data set resulted in the elimination of 95 percent of the 38,000 binding sites predicted upon analysis of the human sequence alone, while it identified 87 percent of the experimentally verified binding sites in this region.

  5. Critical Factors toward Successful R&D Projects in Public Research Centers: a Primer

    Directory of Open Access Journals (Sweden)

    A. Barragán-Ocaña

    2013-12-01

    Full Text Available Mexican Public Research Centers (PRCs have become one of the most important actors in technology development for most enterprises they interact with. Nevertheless, knowledge generated and accumulated by PRCs is being underutilized or not utilized at all in the advance of new projects to benefit productive sectors. In this paper we review a number of variables to pinpoint factors that either promote or hinder successful R&D projects; i.e. those transferred to the industry. We conclude that it is feasible to design policies to boost positive factors while preventing or reducing the impact of the negative ones.

  6. rVISTA 2.0: Evolutionary Analysis of Transcription Factor Binding Sites

    Energy Technology Data Exchange (ETDEWEB)

    Loots, G G; Ovcharenko, I

    2004-01-28

    Identifying and characterizing the patterns of DNA cis-regulatory modules represents a challenge that has the potential to reveal the regulatory language the genome uses to dictate transcriptional dynamics. Several studies have demonstrated that regulatory modules are under positive selection and therefore are often conserved between related species. Using this evolutionary principle we have created a comparative tool, rVISTA, for analyzing the regulatory potential of noncoding sequences. The rVISTA tool combines transcription factor binding site (TFBS) predictions, sequence comparisons and cluster analysis to identify noncoding DNA regions that are highly conserved and present in a specific configuration within an alignment. Here we present the newly developed version 2.0 of the rVISTA tool that can process alignments generated by both zPicture and PipMaker alignment programs or use pre-computed pairwise alignments of seven vertebrate genomes available from the ECR Browser. The rVISTA web server is closely interconnected with the TRANSFAC database, allowing users to either search for matrices present in the TRANSFAC library collection or search for user-defined consensus sequences. rVISTA tool is publicly available at http://rvista.dcode.org/.

  7. Myxoma virus M130R is a novel virulence factor required for lethal myxomatosis in rabbits.

    Science.gov (United States)

    Barrett, John W; Werden, Steven J; Wang, Fuan; McKillop, William M; Jimenez, June; Villeneuve, Danielle; McFadden, Grant; Dekaban, Gregory A

    2009-09-01

    Myxoma virus (MV) is a highly lethal, rabbit-specific poxvirus that induces a disease called myxomatosis in European rabbits. In an effort to understand the function of predicted immunomodulatory genes we have deleted various viral genes from MV and tested the ability of these knockout viruses to induce lethal myxomatosis. MV encodes a unique 15 kD cytoplasmic protein (M130R) that is expressed late (12h post infection) during infection. M130R is a non-essential gene for MV replication in rabbit, monkey or human cell lines. Construction of a targeted gene knockout virus (vMyx130KO) and infection of susceptible rabbits demonstrate that the M130R knockout virus is attenuated and that loss of M130R expression allows the rabbit host immune system to effectively respond to and control the lethal effects of MV. M130R expression is a bona fide poxviral virulence factor necessary for full and lethal development of myxomatosis.

  8. Exploration of ecological factors related to the spatial heterogeneity of tuberculosis prevalence in P. R. China

    Directory of Open Access Journals (Sweden)

    Xin-Xu Li

    2014-06-01

    Full Text Available Background: The current prevalence of tuberculosis (TB in the People's Republic of China (P. R. China demonstrates geographical heterogeneities, which show that the TB prevalence in the remote areas of Western China is more serious than that in the coastal plain of Eastern China. Although a lot of ecological studies have been applied in the exploration on the regional difference of disease risks, there is still a paucity of ecological studies on TB prevalence in P. R. China. Objective: To understand the underlying factors contributing to the regional inequity of TB burden in P. R. China by using an ecological approach and, thus, aiming to provide a basis to eliminate the TB spatial heterogeneity in the near future. Design: Latent ecological variables were identified by using exploratory factor analysis from data obtained from four sources, i.e. the databases of the National TB Control Programme (2001–2010 in P. R. China, the China Health Statistical Yearbook during 2002–2011, the China Statistical Yearbook during 2002–2011, and the provincial government websites in 2013. Partial least squares path modelling was chosen to construct the structural equation model to evaluate the relationship between TB prevalence and ecological variables. Furthermore, a geographically weighted regression model was used to explore the local spatial heterogeneity in the relationships. Results: The latent ecological variables in terms of ‘TB prevalence’, ‘TB investment’, ‘TB service’, ‘health investment’, ‘health level’, ‘economic level’, ‘air quality’, ‘climatic factor’ and ‘geographic factor’ were identified. With the exception of TB service and health levels, other ecological factors had explicit and significant impacts on TB prevalence to varying degrees. Additionally, each ecological factor had different impacts on TB prevalence in different regions significantly. Conclusion: Ecological factors that were found predictive

  9. Influencing factors on microbubble ozonation treatment of acid red 3R wastewater

    Directory of Open Access Journals (Sweden)

    Yurong YA

    2017-08-01

    Full Text Available The microbubble ozonation was used to treat acid red 3R wastewater in order to investigate the influencing factors on its performance. The effects of ozone dose, initial acid red 3R concentration and activated carbon on the performance of microbubble ozonation treatment of acid red 3R wastewater are investigated. The decolorization rate, TOC removal rate, pH variation and ozone utilization efficiency in the microbubble ozonation treatment are compared under different treatment conditions. The results indicate that when increasing ozone dose or decreasing initial acid red 3R concentration, both decolorization rate and TOC removal rate of acid red 3R wastewater increase, but ozone utilization efficiency decreases. The coal-based activated carbon shows strong catalytic activity for microbubble ozonation, which could enhance the decolorization rate and TOC removal rate of acid red 3R wastewater. The better performance of microbubble ozonation treatment is achieved when the ozone dose is 48.3 mg/min and the initial acid red 3R mass concentration is 100 mg/L. Under these conditions, the decolorization efficiency reaches to 100% after treatment for 30 min, the TOC removal efficiency reaches to 78.0% after treatment for 120 min, the reaction rate constant of TOC removal is 0.015 min-1 and the ozone utilization efficiency is higher than 99%. With addition of the coal-based activated carbon of 5 g/L, the decolorization efficiency reaches to 100% after treatment for 15 min, the TOC removal efficiency reaches to 91.2% after treatment for 120 min and the reaction rate constant of TOC removal increases to 0037 min-1.The accumulation and following degradation of intermediate products of small molecule organic acid happens during treatment process, and as a result, the solution pH decreases initially and then increases. Therefore, the optimization of influencing factors for microbubble ozonation could increase both contaminant removal

  10. Coagulation factor VII R353Q polymorphism and the risk of puerperal cerebral venous thrombosis.

    Science.gov (United States)

    Kruthika-Vinod, T P; Nagaraja, Dindagur; Christopher, Rita

    2012-01-01

    Puerperal cerebral venous thrombosis (CVT) is a relatively common form of stroke in young women in India. The blood coagulation factor VII (FVII) R353Q polymorphism increases the risk for venous thrombosis. Our aim was to investigate the association of FVII R353Q polymorphism with the risk of puerperal CVT. A total of 100 women with puerperal CVT and 102 age-matched women without postpartum complications were investigated. FVII R353Q genotypes were identified using restriction fragment length polymorphism analysis. Our results showed that the homozygous FVII 353QQ genotype was present in 9% and 8% of patients and controls, respectively; and 42% of patients and 31.4% of controls had the heterozygous 353RQ genotype (odds ratio = 1.55, 95% confidence interval = 0.89-2.70; p = 0.243). Our findings suggest that the FVII R353Q polymorphism is not associated with increased risk for CVT occurring during the puerperal period in Indian women.

  11. Th1 stimulatory proteins of Leishmania donovani: comparative cellular and protective responses of rTriose phosphate isomerase, rProtein disulfide isomerase and rElongation factor-2 in combination with rHSP70 against visceral leishmaniasis.

    Science.gov (United States)

    Jaiswal, Anil Kumar; Khare, Prashant; Joshi, Sumit; Kushawaha, Pramod Kumar; Sundar, Shyam; Dube, Anuradha

    2014-01-01

    In visceral leishmaniasis, the recovery from the disease is always associated with the generation of Th1-type of cellular responses. Based on this, we have previously identified several Th1-stimulatory proteins of Leishmania donovani -triose phosphate isomerase (TPI), protein disulfide isomerase (PDI) and elongation factor-2 (EL-2) etc. including heat shock protein 70 (HSP70) which induced Th1-type of cellular responses in both cured Leishmania patients/hamsters. Since, HSPs, being the logical targets for vaccines aimed at augmenting cellular immunity and can be early targets in the immune response against intracellular pathogens; they could be exploited as vaccine/adjuvant to induce long-term immunity more effectively. Therefore, in this study, we checked whether HSP70 can further enhance the immunogenicity and protective responses of the above said Th1-stimulatory proteins. Since, in most of the studies, immunogenicity of HSP70 of L. donovani was assessed in native condition, herein we generated recombinant HSP70 and tested its potential to stimulate immune responses in lymphocytes of cured Leishmania infected hamsters as well as in the peripheral blood mononuclear cells (PBMCs) of cured patients of VL either individually or in combination with above mentioned recombinant proteins. rLdHSP70 alone elicited strong cellular responses along with remarkable up-regulation of IFN-γ and IL-12 cytokines and extremely lower level of IL-4 and IL-10. Among the various combinations, rLdHSP70 + rLdPDI emerged as superior one augmenting improved cellular responses followed by rLdHSP70 + rLdEL-2. These combinations were further evaluated for its protective potential wherein rLdHSP70 + rLdPDI again conferred utmost protection (∼80%) followed by rLdHSP70 + rLdEL-2 (∼75%) and generated a strong cellular immune response with significant increase in the levels of iNOS transcript as well as IFN-γ and IL-12 cytokines which was further supported by the high level of IgG2 antibody

  12. Replication Fork Protection Factors Controlling R-Loop Bypass and Suppression.

    Science.gov (United States)

    Chang, Emily Yun-Chia; Stirling, Peter C

    2017-01-14

    Replication-transcription conflicts have been a well-studied source of genome instability for many years and have frequently been linked to defects in RNA processing. However, recent characterization of replication fork-associated proteins has revealed that defects in fork protection can directly or indirectly stabilize R-loop structures in the genome and promote transcription-replication conflicts that lead to genome instability. Defects in essential DNA replication-associated activities like topoisomerase, or the minichromosome maintenance (MCM) helicase complex, as well as fork-associated protection factors like the Fanconi anemia pathway, both appear to mitigate transcription-replication conflicts. Here, we will highlight recent advances that support the concept that normal and robust replisome function itself is a key component of mitigating R-loop coupled genome instability.

  13. Integrating a Storage Factor into R-NARX Neural Networks for Flood Forecasts

    Science.gov (United States)

    Chou, Po-Kai; Chang, Li-Chiu; Chang, Fi-John; Shih, Ban-Jwu

    2017-04-01

    Because mountainous terrains and steep landforms rapidly accelerate the speed of flood flow in Taiwan island, accurate multi-step-ahead inflow forecasts during typhoon events for providing reliable information benefiting the decision-makings of reservoir pre-storm release and flood-control operation are considered crucial and challenging. Various types of artificial neural networks (ANNs) have been successfully applied in hydrological fields. This study proposes a recurrent configuration of the nonlinear autoregressive with exogenous inputs (NARX) network, called R-NARX, with various effective inputs to forecast the inflows of the Feitsui Reservoir, a pivot reservoir for water supply to Taipei metropolitan in Taiwan, during typhoon periods. The proposed R-NARX is constructed based on the recurrent neural network (RNN), which is commonly used for modelling nonlinear dynamical systems. A large number of hourly rainfall and inflow data sets collected from 95 historical typhoon events in the last thirty years are used to train, validate and test the models. The potential input variables, including rainfall in previous time steps (one to six hours), cumulative rainfall, the storage factor and the storage function, are assessed, and various models are constructed with their reliability and accuracy being tested. We find that the previous (t-2) rainfall and cumulative rainfall are crucial inputs and the storage factor and the storage function would also improve the forecast accuracy of the models. We demonstrate that the R-NARX model not only can accurately forecast the inflows but also effectively catch the peak flow without adopting observed inflow data during the entire typhoon period. Besides, the model with the storage factor is superior to the model with the storage function, where its improvement can reach 24%. This approach can well model the rainfall-runoff process for the entire flood forecasting period without the use of observed inflow data and can provide

  14. (R)-β-lysine-modified elongation factor P functions in translation elongation

    DEFF Research Database (Denmark)

    Bullwinkle, Tammy J; Zou, S Betty; Rajkovic, Andrei

    2013-01-01

    Post-translational modification of bacterial elongation factor P (EF-P) with (R)-β-lysine at a conserved lysine residue activates the protein in vivo and increases puromycin reactivity of the ribosome in vitro. The additional hydroxylation of EF-P at the same lysine residue by the YfcM protein has......-(β)-lysyl-EF-P showed 30% increased puromycin reactivity but no differences in dipeptide synthesis rates when compared with the β-lysylated form. Unlike disruption of the other genes required for EF-P modification, deletion of yfcM had no phenotypic consequences in Salmonella. Taken together, our findings indicate...

  15. Recombinant factor VIII Fc (rFVIIIFc) fusion protein reduces immunogenicity and induces tolerance in hemophilia A mice.

    Science.gov (United States)

    Krishnamoorthy, Sriram; Liu, Tongyao; Drager, Douglas; Patarroyo-White, Susannah; Chhabra, Ekta Seth; Peters, Robert; Josephson, Neil; Lillicrap, David; Blumberg, Richard S; Pierce, Glenn F; Jiang, Haiyan

    2016-03-01

    Anti-factor VIII (FVIII) antibodies is a major complication of FVIII replacement therapy for hemophilia A. We investigated the immune response to recombinant human factor VIII Fc (rFVIIIFc) in comparison to BDD-rFVIII and full-length rFVIII (FL-rFVIII) in hemophilia A mice. Repeated administration of therapeutically relevant doses of rFVIIIFc in these mice resulted in significantly lower antibody responses to rFVIII compared to BDD-rFVIII and FL-rFVIII and reduced antibody production upon subsequent challenge with high doses of rFVIIIFc. The induction of a tolerogenic response by rFVIIIFc was associated with higher percentage of regulatory T-cells, a lower percentage of pro-inflammatory splenic T-cells, and up-regulation of tolerogenic cytokines and markers. Disruption of Fc interactions with either FcRn or Fcγ receptors diminished tolerance induction, suggesting the involvement of these pathways. These results indicate that rFVIIIFc reduces immunogenicity and imparts tolerance to rFVIII demonstrating that recombinant therapeutic proteins may be modified to influence immunogenicity and facilitate tolerance.

  16. Computing the R of the QR factorization of tall and skinny matrices using MPI_Reduce

    CERN Document Server

    Langou, Julien

    2010-01-01

    A QR factorization of a tall and skinny matrix with n columns can be represented as a reduction. The operation used along the reduction tree has in input two n-by-n upper triangular matrices and in output an n-by-n upper triangular matrix which is defined as the R factor of the two input matrices stacked the one on top of the other. This operation is binary, associative, and commutative. We can therefore leverage the MPI library capabilities by using user-defined MPI operations and MPI_Reduce to perform this reduction. The resulting code is compact and portable. In this context, the user relies on the MPI library to select a reduction tree appropriate for the underlying architecture.

  17. Over-expression of a subgroup 4 R2R3 type MYB transcription factor gene from Leucaena leucocephala reduces lignin content in transgenic tobacco.

    Science.gov (United States)

    Omer, Sumita; Kumar, Santosh; Khan, Bashir M

    2013-01-01

    KEY MESSAGE : LlMYB1 , a subgroup 4 R2R3-type MYB transcription factor gene from Leucaena leucocephala appears to be a repressor of lignin biosynthesis pathway by regulating the transcription of general phenylpropanoid pathway genes. R2R3MYB transcription factors are known to play a wide role in regulating the phenylpropanoid pathway in plants. In this study, we report isolation, cloning and characterization of an R2R3MYB transcription factor gene (LlMYB1) from an economically important tree species, Leucaena leucocephala. LlMYB1 consists of 705 bp coding sequence corresponding to 235 amino acids. Sequence alignment revealed that the N-terminal (MYB) domain of the gene shares up to 95 % similarity with subgroup 4 (Sg4) members of R2R3Myb gene family functionally known to be lignin repressors. Highly divergent C-terminal region of the gene carried an ERF-associated amphiphilic repression (EAR) motif, another characteristic of the Sg4. The gene was phylogenetically grouped closest with AmMYB308, a known repressor of monolignol biosynthetic pathway genes. Spatio-temporal expression studies at different ages of seedlings using quantitative real-time PCR (QRT-PCR) showed highest transcript level of the gene in 10 day old stem tissues. Over-expression of the gene in transgenic tobacco showed statistically significant decline in the transcript levels of the general phenylpropanoid pathway genes and reduction in lignin content. Our study suggests that LlMYB1 might be playing the role of a repressor of lignin biosynthesis in L. leucocephala.

  18. Fasting insulin at baseline influences the number of cardiometabolic risk factors and R-R interval at 3years in a healthy population: the RISC Study.

    Science.gov (United States)

    Pataky, Z; Golay, A; Laville, M; Disse, E; Mitrakou, A; Guidone, C; Gabriel, R; Bobbioni-Harsch, E

    2013-09-01

    This was a cross-sectional and longitudinal study of factors contributing to the number of cardiometabolic risk factors, common carotid artery intima-media thickness (CCA-IMT) and R-R interval in clinically healthy subjects without diabetes. Anthropometric and cardiometabolic parameters were measured in the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) Study cohort at baseline (n=1211) and 3years later (n=974). At baseline, insulin sensitivity was assessed by the euglycaemic clamp technique. The CCA-IMT was echographically measured and the R-R interval was electrocardiographically evaluated at baseline and at the 3-year follow-up. Higher baseline BMI, fasting insulin and tobacco use as well as greater changes in BMI and fasting insulin but lower adiponectin levels, were associated with a greater number of cardiometabolic risk factors at the 3-year follow-up independently of insulin sensitivity (all Pfasting insulin, whereas higher fasting insulinaemia and its 3-year changes were significantly associated with a smaller R-R interval (P=0.005 and P=0.002, respectively). These relationships were independent of baseline age, gender, BMI, adiponectin, insulin sensitivity, tobacco use and physical activity. In clinically healthy subjects, fasting insulinaemia, adiponectin and lifestyle parameters are related to the presence of one or two cardiometabolic risk factors before criteria for the metabolic syndrome are met. These results underline the importance of fasting insulinaemia as an independent cardiometabolic risk factor at an early stage of disease development in a healthy general population. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  19. Studies with the human cohesin establishment factor, ChlR1. Association of ChlR1 with Ctf18-RFC and Fen1.

    Science.gov (United States)

    Farina, Andrea; Shin, Jae-Ho; Kim, Do-Hyung; Bermudez, Vladimir P; Kelman, Zvi; Seo, Yeon-Soo; Hurwitz, Jerard

    2008-07-25

    Human ChlR1 (hChlR1), a member of the DEAD/DEAH subfamily of helicases, was shown to interact with components of the cohesin complex and play a role in sister chromatid cohesion. In order to study the biochemical and biological properties of hChlR1, we purified the protein from 293 cells and demonstrated that hChlR1 possesses DNA-dependent ATPase and helicase activities. This helicase translocates on single-stranded DNA in the 5' to 3' direction in the presence of ATP and, to a lesser extent, dATP. Its unwinding activity requires a 5'-singlestranded region for helicase loading, since flush-ended duplex structures do not support unwinding. The helicase activity of hChlR1 is capable of displacing duplex regions up to 100 bp, which can be extended to 500 bp by RPA or the cohesion establishment factor, the Ctf18-RFC (replication factor C) complex. We show that hChlR1 interacts with the hCtf18-RFC complex, human proliferating cell nuclear antigen, and hFen1. The interactions between Fen1 and hChlR1 stimulate the flap endonuclease activity of Fen1. Selective depletion of either hChlR1 or Fen1 by targeted small interfering RNA treatment results in the precocious separation of sister chromatids. These findings are consistent with a role of hChlR1 in the establishment of sister chromatid cohesion and suggest that its action may contribute to lagging strand processing events important in cohesion.

  20. Regulation of root hair cell differentiation by R3 MYB transcription factors in tomato and Arabidopsis.

    Science.gov (United States)

    Tominaga-Wada, Rumi; Wada, Takuji

    2014-01-01

    CAPRICE (CPC) encodes a small protein with an R3 MYB motif and regulates root hair and trichome cell differentiation in Arabidopsis thaliana. Six additional CPC-like MYB proteins including TRIPTYCHON (TRY), ENHANCER OF TRY AND CPC1 (ETC1), ENHANCER OF TRY AND CPC2 (ETC2), ENHANCER OF TRY AND CPC3/CPC-LIKE MYB3 (ETC3/CPL3), TRICHOMELESS1 (TCL1), and TRICHOMELESS2/CPC-LIKE MYB4 (TCL2/CPL4) also have the ability to regulate root hair and/or trichome cell differentiation in Arabidopsis. In this review, we describe our latest findings on how CPC-like MYB transcription factors regulate root hair cell differentiation. Recently, we identified the tomato SlTRY gene as an ortholog of the Arabidopsis TRY gene. Transgenic Arabidopsis plants harboring SlTRY produced more root hairs, a phenotype similar to that of 35S::CPC transgenic plants. CPC is also known to be involved in anthocyanin biosynthesis. Anthocyanin accumulation was repressed in the SlTRY transgenic plants, suggesting that SlTRY can also influence anthocyanin biosynthesis. We concluded that tomato and Arabidopsis partially use similar transcription factors for root hair cell differentiation, and that a CPC-like R3 MYB may be a key common regulator of plant root-hair development.

  1. Root hair cell differentiation by tomato and Arabidopsis R3 MYB transcription factors

    Directory of Open Access Journals (Sweden)

    Rumi eTominaga-Wada

    2014-03-01

    Full Text Available CAPRICE (CPC encodes a small protein with an R3 MYB motif and regulates root hair and trichome cell differentiation in Arabidopsis thaliana. Six additional CPC-like MYB proteins including TRIPTYCHON (TRY, ENHANCER OF TRY AND CPC1 (ETC1, ENHANCER OF TRY AND CPC2 (ETC2, ENHANCER OF TRY AND CPC3/ CPC-LIKE MYB3 (ETC3/CPL3, TRICHOMELESS1 (TCL1 and TRICHOMELESS2/CPC-LIKE MYB4 (TCL2/CPL4 also have the ability to regulate root hair and/or trichome cell differentiation in Arabidopsis. In this review, we describe our latest findings on how CPC-like MYB transcription factors regulate root hair cell differentiation. Recently, we identified the tomato SlTRY gene as an ortholog of the Arabidopsis TRY gene. Transgenic Arabidopsis plants harboring SlTRY produced more root hairs, a phenotype similar to that of 35S::CPC transgenic plants. CPC is also known to be involved in anthocyanin biosynthesis. Anthocyanin accumulation was repressed in the SlTRY transgenic plants, suggesting that SlTRY can also influence anthocyanin biosynthesis. We concluded that tomato and Arabidopsis partially use similar transcription factors for root hair cell differentiation, and that a CPC-like R3 MYB may be a key common regulator of plant root-hair development.

  2. Evaluating response modification factor (R for some types of steel structure

    Directory of Open Access Journals (Sweden)

    Doralba Valencia Restrepo

    2010-04-01

    Full Text Available Response modification factor (R, tabulated in the Colombian Design Code as NSR-98, is used in this paper for eva-luating internal member forces produced by design earthquake action on steel structures and the inconsistencies pre-sent when designing structures when 1% drift limits must be complied with. The article presents the design of 45 frames corresponding to the seismic resistance system of 5 buildings: 15 special moment frames (SMF, 15 special concentrically-braced frames (CBF and 15 eccentrically-braced frames (EBF. External loads and their combination were used in estimating internal loads and rigidity demands (1% drift were evaluated in line with NSR-98 requi-rements. Member strength requirements were evaluated by using the AISC-2005 seismic provisions for steel structu-red buildings. Modal pushover analysis was used for evaluating the response modification factor for the 45 given frames at different structural performance levels. It was found that this factor was not constant for any of the three structural systems (SMF, CBF and EBF suggested by NSR-98 and that the values of the response modification factor found in the present investigation were smaller than those tabulated in this design code governing everyday structural design. This would lead to significant errors being made in evaluating design forces, not only in the structures but in the support elements (base-plates, foundations, shear walls and any structures attached to buildings constructed in line with the seismic resistance system.

  3. Conifer R2R3-MYB transcription factors: sequence analyses and gene expression in wood-forming tissues of white spruce (Picea glauca

    Directory of Open Access Journals (Sweden)

    Grima-Pettenati Jacqueline

    2007-03-01

    Full Text Available Abstract Background Several members of the R2R3-MYB family of transcription factors act as regulators of lignin and phenylpropanoid metabolism during wood formation in angiosperm and gymnosperm plants. The angiosperm Arabidopsis has over one hundred R2R3-MYBs genes; however, only a few members of this family have been discovered in gymnosperms. Results We isolated and characterised full-length cDNAs encoding R2R3-MYB genes from the gymnosperms white spruce, Picea glauca (13 sequences, and loblolly pine, Pinus taeda L. (five sequences. Sequence similarities and phylogenetic analyses placed the spruce and pine sequences in diverse subgroups of the large R2R3-MYB family, although several of the sequences clustered closely together. We searched the highly variable C-terminal region of diverse plant MYBs for conserved amino acid sequences and identified 20 motifs in the spruce MYBs, nine of which have not previously been reported and three of which are specific to conifers. The number and length of the introns in spruce MYB genes varied significantly, but their positions were well conserved relative to angiosperm MYB genes. Quantitative RTPCR of MYB genes transcript abundance in root and stem tissues revealed diverse expression patterns; three MYB genes were preferentially expressed in secondary xylem, whereas others were preferentially expressed in phloem or were ubiquitous. The MYB genes expressed in xylem, and three others, were up-regulated in the compression wood of leaning trees within 76 hours of induction. Conclusion Our survey of 18 conifer R2R3-MYB genes clearly showed a gene family structure similar to that of Arabidopsis. Three of the sequences are likely to play a role in lignin metabolism and/or wood formation in gymnosperm trees, including a close homolog of the loblolly pine PtMYB4, shown to regulate lignin biosynthesis in transgenic tobacco.

  4. Light-induced carotenogenesis in Myxococcus xanthus: functional characterization of the ECF sigma factor CarQ and antisigma factor CarR.

    Science.gov (United States)

    Browning, Douglas F; Whitworth, David E; Hodgson, David A

    2003-04-01

    Illumination of dark-grown Myxococcus xanthus with blue light leads to the induction of carotenoid synthesis. Central to this response is the activation of the light-inducible promoter, PcarQRS, and the transcription of three downstream genes, carQ, carR and carS. Sequence analysis predicted that CarQ is a member of the ECF (extracytoplasmic function) subfamily of RNA polymerase sigma factors, and that CarR is an inner membrane protein. Genetic analysis strongly implied that CarR is an antisigma factor that sequesters CarQ in a transcriptionally inactive complex. Using in vitro transcription run-off assays, we present biochemical evidence that CarQ functions as a bacterial sigma factor and is responsible for transcription initiation at PcarQRS. Similar experiments using the crtI promoter failed to implicate CarQ in direct transcription of the crtI gene. Experiments using the yeast two-hybrid system demonstrated a protein-protein interaction between CarQ and CarR, providing evidence of a CarQ-CarR complex. The yeast two-hybrid system data also indicated that CarR is capable of oligomerization. Fractionation of M. xanthus membranes with the detergent sarkosyl showed that CarR was associated with the inner membrane. Furthermore, CarR was found to be unstable in illuminated stationary phase cells, providing a possible mechanism by which the CarR-CarQ complex is disrupted.

  5. Evaluation of SNPs in miR-196-a2, miR-27a and miR-146a as risk factors of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Renata Hezova; Rostislav Vyzula,; Ondrej Slaby; Alena Kovarikova; Julie Bienertova-Vasku; Milana Sachlova; Martina Redova; Anna Vasku; Marek Svoboda; Lenka Radova; Igor Kiss,

    2012-01-01

    AIM:To investigate whether selected single nucleotide polymorphisms (SNPs) in miR-196a2,miR-27a and miR146a genes are associated with sporadic colorectal cancer (CRC).METHODS:In order to investigate the effect of these SNPs in CRC,we performed a case-control study of 197 cases of sporadic CRC and 212 cancer-free controls originating from the Central-European Caucasian population using TaqMan Real-Time polymerase chain reaction and allelic discrimination analysis.RESULTS:The genotype and allele frequencies of SNPs were compared between the cases and the controis.None of the performed analysis showed any statistically significant results.CONCLUSION:Our data suggest a lack of association between rs11614913,rs895819 and rs2910164 and colorectal cancer risk in the Central-European Caucasian population,a population with an extremely high incidence of sporadic colorectal cancer.

  6. Charge-density analysis of 1-nitroindoline: refinement quality using free R factors and restraints.

    Science.gov (United States)

    Zarychta, Bartosz; Zaleski, Jacek; Kyzioł, Janusz; Daszkiewicz, Zdzisław; Jelsch, Christian

    2011-06-01

    Nitramines and related N-nitro compounds have attracted significant attention owing to their use in rocket fuel and as explosives. The charge density of 1-nitroindoline was determined experimentally and from theoretical calculations. Electron-density refinements were performed using the multipolar atom formalism. In order to design the ideal restraint strategy for the charge-density parameters, R-free analyses were performed involving a series of comprehensive refinements. Different weights were applied to the charge-density restraints, namely the similarity between chemically equivalent atoms and local symmetry. Additionally, isotropic thermal motion and an anisotropic model calculated by rigid-body analysis were tested on H atoms. The restraint weights which resulted in the lowest values of the averaged R-free factors and the anisotropic H-atom model were considered to yield the best charge density and were used in the final refinement. The derived experimental charge density along with intra- and intermolecular interactions was analysed and compared with theoretical calculations, notably with respect to the symmetry of multipole parameters. A comparison of different refinements suggests that the appropriate weighting scheme applied to charge-density restraints can reduce the observed artefacts. The topological bond orders of the molecule were calculated.

  7. Rasch modeling and confirmatory factor analysis of the systemizing quotient-revised (SQ-R) scale.

    Science.gov (United States)

    Allison, Carrie; Baron-Cohen, Simon; Stone, Mark H; Muncer, Steven J

    2015-01-01

    This study assessed the dimensionality of the Systemizing Quotient-Revised (SQ-R), a measure of how strong a person's interest is in systems, using two statistical approaches: Rasch modeling and Confirmatory Factor Analysis (CFA). Participants included N = 675 with an autism spectrum condition (ASC), N = 1369 family members of people with ASC, and N = 2014 typical controls. Data were applied to the Rasch model (Rating Scale) using WINSTEPS. The data fit the Rasch model quite well lending support to the idea that systemizing could be seen as unidimensional. Reliability estimates were .99 for items and .92 for persons. A CFA parceling approach confirmed that a unidimensional model fit the data. There was, however, differential functioning by sex in some of these items. An abbreviated 44-item version of the scale, consisting of items without differential item functioning by sex was developed. This shorter scale also was tested from a Rasch perspective and confirmed through CFA. All measures showed differences on total scale scores between those participants with and without ASC (d = 0.71, p < .005), and between sexes (d = 0.53, p < .005). We conclude that the SQ-R is an appropriate measure of systemizing which can be measured along a single dimension.

  8. Success Factors in Integrated Natural Resource Management R&D: Lessons from Practice

    Directory of Open Access Journals (Sweden)

    Jürgen Hagmann

    2002-01-01

    Full Text Available This paper analyzes integrated natural resource management (INRM lessons and success factors based on a practical case study over more than 10 years in Zimbabwe. The work was geared toward enhancing the adaptive management capacity of the stakeholders in their resource-use systems. One main result was the development and institutionalization of an approach for participatory and integrated NRM research and extension. The INRM approach described is grounded in a learning paradigm and a combination of theories: the constructivist perspective to development, systemic intervention, and learning process approaches. Participatory action research and experiential learning, in which researchers engage themselves as actors rather than neutral analysts in an R&D process to explore the livelihood system and develop appropriate solutions together with the resource users, has shown high potential. However, this should be guided by a clear strategy, impact orientation, and high-quality process facilitation at different levels. The case study revealed the importance of a "reflective practitioner" approach by all actors. More effective response to the challenges of increasing complexity in NRM requires a shift in thinking from the linearity of research-extension-farmer to alternative, multiple-actor institutional arrangements and innovation systems. To overcome the weak attribution of research outcomes to actual impact, it also suggests an alternative to conventional impact assessment in INRM R&D interventions.

  9. Correlation between Slug transcription factor and miR-221 in MDA-MB-231 breast cancer cells

    Directory of Open Access Journals (Sweden)

    Lambertini Elisabetta

    2012-10-01

    Full Text Available Abstract Background Breast cancer and its metastatic progression is mainly directed by epithelial to mesenchymal transition (EMT, a phenomenon supported by specific transcription factors and miRNAs. Methods In order to investigate a possible correlation between Slug transcription factor and miR-221, we performed Slug gene silencing in MDA-MB-231 breast cancer cells and evaluated the expression of genes involved in supporting the breast cancer phenotype, using qRT-PCR and Western blot analysis. Chromatin immunoprecipitation and wound healing assays were employed to determine a functional link between these two molecules. Results We showed that Slug silencing significantly decreased the level of miR-221 and vimentin, reactivated Estrogen Receptor α and increased E-cadherin and TRPS1 expression. We demonstrated that miR-221 is a Slug target gene, and identified a specific region of miR-221 promoter that is transcriptionally active and binds the transcription factor Slug “in vivo”. In addition, we showed that in Slug-silenced cells, wich retained residual miR-221 (about 38%, cell migration was strongly inhibited. Cell migration was inhibited, but to a less degree, following complete knockdown of miR-221 expression by transfection with antagomiR-221. Conclusions We report for the first time evidence of a correlation between Slug transcription factor and miR-221 in breast cancer cells. These studies suggest that miR-221 expression is, in part, dependent on Slug in breast cancer cells, and that Slug plays a more important role than miR-221 in cell migration and invasion.

  10. MicroRNA miR-8 regulates multiple growth factor hormones produced from Drosophila fat cells.

    Science.gov (United States)

    Lee, G J; Jun, J W; Hyun, S

    2015-06-01

    Metabolic organs such as the liver and adipose tissue produce several peptide hormones that influence metabolic homeostasis. Fat bodies, the Drosophila counterpart of liver and adipose tissues, have been thought to analogously secrete several hormones that affect organismal physiology, but their identity and regulation remain poorly understood. Previous studies have indicated that microRNA miR-8, functions in the fat body to non-autonomously regulate organismal growth, suggesting that fat body-derived humoral factors are regulated by miR-8. Here, we found that several putative peptide hormones known to have mitogenic effects are regulated by miR-8 in the fat body. Most members of the imaginal disc growth factors and two members of the adenosine deaminase-related growth factors are up-regulated in the absence of miR-8. Drosophila insulin-like peptide 6 (Dilp6) and imaginal morphogenesis protein-late 2 (Imp-L2), a binding partner of Dilp, are also up-regulated in the fat body of miR-8 null mutant larvae. The fat body-specific reintroduction of miR-8 into the miR-8 null mutants revealed six peptides that showed fat-body organ-autonomous regulation by miR-8. Amongst them, only Imp-L2 was found to be regulated by U-shaped, the miR-8 target for body growth. However, a rescue experiment by knockdown of Imp-L2 indicated that Imp-L2 alone does not account for miR-8's control over the insect's growth. Our findings suggest that multiple peptide hormones regulated by miR-8 in the fat body may collectively contribute to Drosophila growth. © 2014 The Royal Entomological Society.

  11. AN ALGORITHM FOR CONSTRUCTING ORTHOGONAL ARMLET MULTI-WAVELETS WITH MULTIPLICITY r AND DILATION FACTOR a

    Institute of Scientific and Technical Information of China (English)

    Zhou Xiaohui; Wang Gang; Wang Baoqin

    2011-01-01

    The purpose of this paper is to construct an orthogonal Armlet multi-wavelets with multiplicity r and dilation factor a.Firstly,the definition of Armlets with dilation factor a is proposed in this paper.Based on the Two-scale Similar Transform (TST),the notion of the Para-unitary A-scale Similar Transform (PAST) is introduced,and we also give the transform on the all two-scale matrix symbols of the multi-wavelets with dilation a.Then we show that the PAST and the transform on the matrix symbols of the multi-wavelets keep the orthogonality of the multi-wavelets system.We discuss the condition that a- 1 multi-wavelets corresponding to the multi-scaling functions are all Armlets.After performing the PAST and the transform on the matrix symbols of the multi-wavelets,the multi-scaling function can be balanced and the corresponding multi-wavelets can be Armlets at the same time.The construction of Armlets with high order is also discussed.At last,by a given example,we can conclude that the algorithm is feasible and efficient.

  12. Insulin-like growth factor 1 receptor and response to anti-IGF1R antibody therapy in osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Yu Cao

    Full Text Available Survival outcomes for patients with osteosarcoma (OS have remained stagnant over the past three decades. Insulin-like growth factor 1 receptor (IGF1R is over-expressed in a number of malignancies, and anti-IGF1R antibodies have and are currently being studied in clinical trials. Understanding the molecular aberrations which result in increased tumor response to anti-IGF1R therapy could allow for the selection of patients most likely to benefit from IGF1R targeted therapy.IGF1R mRNA expression was assessed by RT PCR in OS patient primary tumors, cell lines, and xenograft tumors. IGF1R copy number was assessed by 3 approaches: PCR, FISH, and dot blot analysis. Exons 1-20 of IGF1R were sequenced in xenograft tumors and 87 primary OS tumors, and surface expression of IGF1R was assessed by flow cytometry. Levels of mRNA and protein expression, copy number, and mutation status were compared with tumor response to anti-IGF1R antibody therapy in 4 OS xenograft models.IGF1R mRNA is expressed in OS. Primary patient samples and xenograft samples had higher mRNA expression and copy number compared with corresponding cell lines. IGF1R mRNA expression, cell surface expression, copy number, and mutation status were not associated with tumor responsiveness to anti-IGF1R antibody therapy.IGF1R is expressed in OS, however, no clear molecular markers predict response to IGF1R antibody-mediated therapy. Additional pre-clinical studies assessing potential predictive biomarkers and investigating targetable molecular pathways critical to the proliferation of OS cells are needed.

  13. miR-29a suppresses MCF-7 cell growth by downregulating tumor necrosis factor receptor 1.

    Science.gov (United States)

    Zhao, Yiling; Yang, Fenghua; Li, Wenyuan; Xu, Chunyan; Li, Li; Chen, Lifei; Liu, Yancui; Sun, Ping

    2017-02-01

    Tumor necrosis factor receptor 1 is the main receptor mediating many tumor necrosis factor-alpha-induced cellular events. Some studies have shown that tumor necrosis factor receptor 1 promotes tumorigenesis by activating nuclear factor-kappa B signaling pathway, while other studies have confirmed that tumor necrosis factor receptor 1 plays an inhibitory role in tumors growth by inducing apoptosis in breast cancer. Therefore, the function of tumor necrosis factor receptor 1 in breast cancer requires clarification. In this study, we first found that tumor necrosis factor receptor 1 was significantly increased in human breast cancer tissues and cell lines, and knockdown of tumor necrosis factor receptor 1 by small interfering RNA inhibited cell proliferation by arresting the cell cycle and inducing apoptosis. In addition, miR-29a was predicted as a regulator of tumor necrosis factor receptor 1 by TargetScan and was shown to be inversely correlated with tumor necrosis factor receptor 1 expression in human breast cancer tissues and cell lines. Luciferase reporter assay further confirmed that miR-29a negatively regulated tumor necrosis factor receptor 1 expression by binding to the 3' untranslated region. In our functional study, miR-29a overexpression remarkably suppressed cell proliferation and colony formation, arrested the cell cycle, and induced apoptosis in MCF-7 cell. Furthermore, in combination with tumor necrosis factor receptor 1 transfection, miR-29a significantly reversed the oncogenic role caused by tumor necrosis factor receptor 1 in MCF-7 cell. In addition, we demonstrated that miR-29a suppressed MCF-7 cell growth by inactivating the nuclear factor-kappa B signaling pathway and by decreasing cyclinD1 and Bcl-2/Bax protein levels. Taken together, our results suggest that miR-29a is an important regulator of tumor necrosis factor receptor 1 expression in breast cancer and functions as a tumor suppressor by targeting tumor necrosis factor receptor 1 to

  14. Mechanism for regulation of the putrescine utilization pathway by the transcription factor PuuR in Escherichia coli K-12.

    Science.gov (United States)

    Nemoto, Naoki; Kurihara, Shin; Kitahara, Yuzuru; Asada, Kei; Kato, Kenji; Suzuki, Hideyuki

    2012-07-01

    In Escherichia coli, putrescine is metabolized to succinate for use as a carbon and nitrogen source by the putrescine utilization pathway (Puu pathway). One gene in the puu gene cluster encodes a transcription factor, PuuR, which has a helix-turn-helix DNA-binding motif. DNA microarray analysis of an E. coli puuR mutant, in which three amino acid residues in the helix-turn-helix DNA binding motif of PuuR were mutated to alanine to eliminate DNA binding of PuuR, suggested that PuuR is a negative regulator of puu genes. Results of gel shift and DNase I footprint analyses suggested that PuuR binds to the promoter regions of puuA and puuD. The binding of wild-type PuuR to a DNA probe containing PuuR recognition sites was diminished with increasing putrescine concentrations in vitro. These results suggest that PuuR regulates the intracellular putrescine concentration by the transcriptional regulation of genes in the Puu pathway, including puuR itself. The puu gene cluster is found in E. coli and closely related enterobacteria, but this gene cluster is uncommon in other bacterial groups. E. coli and related enterobacteria may have gained the Puu pathway as an adaptation for survival in the mammalian intestine, an environment in which polyamines exist at relatively high concentrations.

  15. The Epidermal Growth Factor Receptor Responsive miR-125a Represses Mesenchymal Morphology in Ovarian Cancer Cells

    Directory of Open Access Journals (Sweden)

    Karen D. Cowden Dahl

    2009-11-01

    Full Text Available The epithelial-to-mesenchymal transition (EMT that occurs during embryonic development is recapitulated during tumor metastasis. Important regulators of this process include growth factors, transcription factors, and adhesion molecules. New evidence suggests that microRNA (miRNA activity contributes to metastatic progression and EMT; however, the mechanisms leading to altered miRNA expression during cancer progression remain poorly understood. Importantly, overexpression of the epidermal growth factor receptor (EGFR in ovarian cancer correlates with poor disease outcome and induces EMT in ovarian cancer cells. We report that EGFR signaling leads to transcriptional repression of the miRNA miR-125a through the ETS family transcription factor PEA3. Overexpression of miR-125a induces conversion of highly invasive ovarian cancer cells from a mesenchymal to an epithelial morphology, suggesting miR-125a is a negative regulator of EMT. We identify AT-rich interactive domain 3B (ARID3B as a target of miR-125a and demonstrate that ARID3B is overexpressed in human ovarian cancer. Repression of miR-125a through growth factor signaling represents a novel mechanism for regulating ovarian cancer invasive behavior.

  16. A R2R3-MYB transcription factor regulates the flavonol biosynthetic pathway in a traditional Chinese medicinal plant, Epimedium sagittatum

    Directory of Open Access Journals (Sweden)

    Wenjun Huang

    2016-07-01

    Full Text Available Flavonols as plant secondary metabolites with vital roles in plant development and defense against UV light, have been demonstrated to be the main bioactive components in the genus Epimedium plants, several species of which are used as materials for Herba Epimedii, an important traditional Chinese medicine. The flavonol biosynthetic pathway genes had been already isolated from E. sagittatum, but a R2R3-MYB transcription factor regulating the flavonol synthesis has not been functionally characterized so far in Epimedium plants. In this study, we isolated and characterized the R2R3-MYB transcription factor EsMYBF1 involved in regulation of the flavonol biosynthetic pathway from E. sagittatum. Sequence analysis indicated that EsMYBF1 belongs to the subgroup 7 of R2R3-MYB family which contains the flavonol-specific MYB regulators identified to date. Transient reporter assay showed that EsMYBF1 strongly activated the promoters of EsF3H (flavanone 3-hydroxylase and EsFLS (flavonol synthase, but not the promoters of EsDFRs (dihydroflavonol 4-reductase and EsANS (anthocyanidin synthase in transiently transformed Nicotiana benthamiana leaves. Both yeast two-hybrid assay and transient reporter assay validated EsMYBF1 to be independent of EsTT8, or AtTT8 bHLH regulators of the flavonoid pathway as cofactors. Ectopic expression of EsMYBF1 in transgenic tobacco resulted in the increased flavonol content and the decreased anthocyanin content in flowers. Correspondingly, the structural genes involved in flavonol synthesis were upregulated in the EsMYBF1 overexpression lines, including NtCHS (chalcone synthase, NtCHI (chalcone isomerase, NtF3H and NtFLS, whereas the late biosynthetic genes of the anthocyanin pathway (NtDFR and NtANS were remarkably downregulated, compared to the controls. These results suggest that EsMYBF1 is a flavonol-specific R2R3-MYB regulator, and involved in regulation of the biosynthesis of the flavonol-derived bioactive components in E

  17. Factors for analysing and improving performance of R&D in Malaysian universities

    NARCIS (Netherlands)

    Ramli, Mohammad Shakir; de Boer, S.J.; de Bruijn, E.J.

    2004-01-01

    This paper presents a model for analysing and improving performance of R&D in Malaysian universities. There are various general models for R&D analysis, but none is specific for improving the performance of R&D in Malaysian universities. This research attempts to fill a gap in the body of knowledge

  18. The Maize enr System of r1 Haplotype–Specific Aleurone Color Enhancement Factors

    Science.gov (United States)

    We describe a family of three dominant r1 haplotype-specific enhancers of aleurone color in Zea mays. Stable alleles of the three enhancement of r1 loci (enr1, enr2 and enr3) intensify aleurone color conferred by certain pale and near-colorless r1 haplotypes. In addition, unstable alleles of enr1 ac...

  19. Recidivism in female offenders: PCL-R lifestyle factor and VRAG show predictive validity in a German sample.

    Science.gov (United States)

    Eisenbarth, Hedwig; Osterheider, Michael; Nedopil, Norbert; Stadtland, Cornelis

    2012-01-01

    A clear and structured approach to evidence-based and gender-specific risk assessment of violence in female offenders is high on political and mental health agendas. However, most data on the factors involved in risk-assessment instruments are based on data of male offenders. The aim of the present study was to validate the use of the Psychopathy Checklist Revised (PCL-R), the HCR-20 and the Violence Risk Appraisal Guide (VRAG) for the prediction of recidivism in German female offenders. This study is part of the Munich Prognosis Project (MPP). It focuses on a subsample of female delinquents (n = 80) who had been referred for forensic-psychiatric evaluation prior to sentencing. The mean time at risk was 8 years (SD = 5 years; range: 1-18 years). During this time, 31% (n = 25) of the female offenders were reconvicted, 5% (n = 4) for violent and 26% (n = 21) for non-violent re-offenses. The predictive validity of the PCL-R for general recidivism was calculated. Analysis with receiver-operating characteristics revealed that the PCL-R total score, the PCL-R antisocial lifestyle factor, the PCL-R lifestyle factor and the PCL-R impulsive and irresponsible behavioral style factor had a moderate predictive validity for general recidivism (area under the curve, AUC = 0.66, p = 0.02). The VRAG has also demonstrated predictive validity (AUC = 0.72, p = 0.02), whereas the HCR-20 showed no predictive validity. These results appear to provide the first evidence that the PCL-R total score and the antisocial lifestyle factor are predictive for general female recidivism, as has been shown consistently for male recidivists. The implications of these findings for crime prevention, prognosis in women, and future research are discussed.

  20. Regulation of secondary cell wall biosynthesis by poplar R2R3 MYB transcription factor PtrMYB152 in Arabidopsis.

    Science.gov (United States)

    Wang, Shucai; Li, Eryang; Porth, Ilga; Chen, Jin-Gui; Mansfield, Shawn D; Douglas, Carl J

    2014-05-23

    Poplar has 192 annotated R2R3 MYB genes, of which only three have been shown to play a role in the regulation of secondary cell wall formation. Here we report the characterization of PtrMYB152, a poplar homolog of the Arabidopsis R2R3 MYB transcription factor AtMYB43, in the regulation of secondary cell wall biosynthesis. The expression of PtrMYB152 in secondary xylem is about 18 times of that in phloem. When expressed in Arabidopsis under the control of either 35S or PtrCesA8 promoters, PtrMYB152 increased secondary cell wall thickness, which is likely caused by increased lignification. Accordingly, elevated expression of genes encoding sets of enzymes in secondary wall biosynthesis were observed in transgenic plants expressing PtrMYB152. Arabidopsis protoplast transfection assays suggested that PtrMYB152 functions as a transcriptional activator. Taken together, our results suggest that PtrMYB152 may be part of a regulatory network activating expression of discrete sets of secondary cell wall biosynthesis genes.

  1. Regulation of secondary cell wall biosynthesis by poplar R2R3 MYB transcription factor PtrMYB152 in Arabidopsis

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Shucai [Northeast Normal Univ., Changchun (China); Univ. of British Columbia, Vancouver, BC (Canada); Li, Eryang [Univ. of British Columbia, Vancouver, BC (Canada); Porth, Ilga [Univ. of British Columbia, Vancouver, BC (Canada); Chen, Jin-Gui [Univ. of British Columbia, Vancouver, BC (Canada); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Mansfield, Shawn D. [Univ. of British Columbia, Vancouver, BC (Canada); Douglas, Carl [Univ. of British Columbia, Vancouver, BC (Canada)

    2014-05-23

    Poplar has 192 annotated R2R3 MYB genes, of which only three have been shown to play a role in the regulation of secondary cell wall formation. Here we report the characterization of PtrMYB152, a poplar homolog of the Arabidopsis R2R3 MYB transcription factor AtMYB43, in the regulation of secondary cell wall biosynthesis. The expression of PtrMYB152 in secondary xylem is about 18 times of that in phloem. When expressed in Arabidopsis under the control of either 35S or PtrCesA8 promoters, PtrMYB152 increased secondary cell wall thickness, which is likely caused by increased lignification. Accordingly, elevated expression of genes encoding sets of enzymes in secondary wall biosynthesis were observed in transgenic plants expressing PtrMYB152. Arabidopsis protoplast transfection assays suggested that PtrMYB152 functions as a transcriptional activator. Taken together, our results suggest that PtrMYB152 may be part of a regulatory network activating expression of discrete sets of secondary cell wall biosynthesis genes.

  2. miR-134 inhibits non-small cell lung cancer growth by targeting the epidermal growth factor receptor.

    Science.gov (United States)

    Qin, Qin; Wei, Furong; Zhang, Jianbo; Wang, Xingwu; Li, Baosheng

    2016-10-01

    The epidermal growth factor receptor (EGFR) is frequently activated in a wide range of solid tumours and represents an important therapeutic target. MicroRNAs (miRNAs) have recently been recognized as a rational and potential modality for anti-EGFR therapies. However, more EGFR-targeting miRNAs need to be explored. In this study, we identified a novel EGFR-targeting miRNA, miRNA-134 (miR-134), in non-small-cell lung cancer (NSCLC) cell lines. Luciferase assays confirmed that EGFR is a direct target of miR-134. In addition, the overexpression of miR-134 inhibited EGFR-related signaling and suppressed NSCLC cells proliferation by inducing cell cycle arrest and/or apoptosis, suggesting that miR-134 functions as a tumour suppressor in NSCLC. Further mechanistic investigation including RNAi and rescue experiments suggested that the down-regulation of EGFR by miR-134 partially contributes to the antiproliferative role of miR-134. Last, in vivo experiments demonstrated that miR-134 suppressed tumour growth of A549 xenograft in nude mice. Taken together, our findings suggest that miR-134 inhibits non-small cell lung cancer growth by targeting the EGFR.

  3. The Revised Two-Factor Study Process Questionnaire (R-SPQ-2F): Exploratory and Confirmatory Factor Analyses at Item Level

    Science.gov (United States)

    Justicia, Fernando; Pichardo, M. Carmen; Cano, Francisco; Berben, A. B. G.; De la Fuente, Jesus

    2008-01-01

    The underlying structure of the Revised Two Factor version of the Study Process Questionnaire (R-SPQ-2F), a 20-item instrument for the evaluation of students' approaches to learning (SAL), was examined at item level using two independent groups of undergraduate students enrolled in the first (n = 314) and last (n = 522) years of their studies. The…

  4. The Revised Two-Factor Study Process Questionnaire (R-SPQ-2F): Exploratory and Confirmatory Factor Analyses at Item Level

    Science.gov (United States)

    Justicia, Fernando; Pichardo, M. Carmen; Cano, Francisco; Berben, A. B. G.; De la Fuente, Jesus

    2008-01-01

    The underlying structure of the Revised Two Factor version of the Study Process Questionnaire (R-SPQ-2F), a 20-item instrument for the evaluation of students' approaches to learning (SAL), was examined at item level using two independent groups of undergraduate students enrolled in the first (n = 314) and last (n = 522) years of their studies. The…

  5. An integrin binding-defective mutant of insulin-like growth factor-1 (R36E/R37E IGF1) acts as a dominant-negative antagonist of the IGF1 receptor (IGF1R) and suppresses tumorigenesis but still binds to IGF1R.

    Science.gov (United States)

    Fujita, Masaaki; Ieguchi, Katsuaki; Cedano-Prieto, Dora M; Fong, Andrew; Wilkerson, Charles; Chen, Jane Q; Wu, Mac; Lo, Su-Hao; Cheung, Anthony T W; Wilson, Machelle D; Cardiff, Robert D; Borowsky, Alexander D; Takada, Yoko K; Takada, Yoshikazu

    2013-07-05

    Insulin-like growth factor-1 (IGF1) is a major therapeutic target for cancer. We recently reported that IGF1 directly binds to integrins (αvβ3 and α6β4) and induces ternary complex formation (integrin-IGF1-IGF1 receptor (IGF1R)) and that the integrin binding-defective mutant of IGF1 (R36E/R37E) is defective in signaling and ternary complex formation. These findings predict that R36E/R37E competes with WT IGF1 for binding to IGF1R and inhibits IGF signaling. Here, we described that excess R36E/R37E suppressed cell viability increased by WT IGF1 in vitro in non-transformed cells. We studied the effect of R36E/R37E on viability and tumorigenesis in cancer cell lines. We did not detect an effect of WT IGF1 or R36E/R37E in cancer cells under anchorage-dependent conditions. However, under anchorage-independent conditions, WT IGF1 enhanced cell viability and induced signals, whereas R36E/R37E did not. Notably, excess R36E/R37E suppressed cell viability and signaling induced by WT IGF1 under anchorage-independent conditions. Using cancer cells stably expressing WT IGF1 or R36E/R37E, we determined that R36E/R37E suppressed tumorigenesis in vivo, whereas WT IGF1 markedly enhanced it. R36E/R37E suppressed the binding of WT IGF1 to the cell surface and the subsequent ternary complex formation induced by WT IGF1. R36E/R37E suppressed activation of IGF1R by insulin. WT IGF1, but not R36E/R37E, induced ternary complex formation with the IGF1R/insulin receptor hybrid. These findings suggest that 1) IGF1 induces signals under anchorage-independent conditions and that 2) R36E/R37E acts as a dominant-negative inhibitor of IGF1R (IGF1 decoy). Our results are consistent with a model in which ternary complex formation is critical for IGF signaling.

  6. Reference factor F{sub (CT)Q} and X ray tube ionization yield R{sub (TUBE)Q}

    Energy Technology Data Exchange (ETDEWEB)

    Quaresma, D.S. [Observatorio Nacional, Rio de Janeiro, RJ (Brazil); Cardoso, R.S.; Peixoto, J.G.P., E-mail: dansq@on.br [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2015-07-01

    The operational facility procedures in diagnostic radiology standardization and calibration, through the relation between the X ray tube current and the ionization chamber current in a radiation quality Q, shown the reference factor F{sub (CT)Q} as the reality estimate to the X ray tube ionization yield, R{sub (TUBE)Q} . (author)

  7. Factors affecting assessment of severity of aggressive incidents: using the Staff Observation Aggression Scale - Revised (SOAS-R) in Japan

    NARCIS (Netherlands)

    Noda, T.; Nijman, H.L.I.; Sugiyama, N.; Tsujiwaki, K.; Putkonen, H.; Sailas, E.; Kontio, R.; Ito, H.; Joffe, G.

    2012-01-01

    Accessible summary Consumer gender and age, and nurse gender influenced the perception of overall severity of aggressive incidents, in addition to the aggression data provided by the Staff Observation Aggression Scale Revised (SOAS-R) scores. The factors influencing assessments of aggression inciden

  8. Form factors of the transitions {gamma}{sup *}{pi}{sup 0} {r_arrow} {gamma} and {gamma}{sup *}{eta}{r_arrow}{gamma}

    Energy Technology Data Exchange (ETDEWEB)

    Afanasev, A. [Continuous Electron Beam Accelerator Facility, Newport News, VA (United States)

    1994-04-01

    The author discusses possibilities to study {gamma}*{pi}{sup 0} and {gamma}*{eta} {r_arrow} {gamma} transition form factors at CEBAF energies. The author shows that for 4 GeV electron beam, these form factors can be measured at CEBAF for the 4-momentum transfers Q{sup 2} {le} 2.5 (GeV/c){sup 2} using virtual Compton scattering on the proton and nuclear target in the kinematic regime of low momentum transfers to the target. These measurements can be extended to Q{sup 2} {le} 4.0 (GeV/c){sup 2} using the electron beam with the energy 6 GeV.

  9. Potential language and attentional networks revealed through factor analysis of rCBF data measured with SPECT

    DEFF Research Database (Denmark)

    McLaughlin, T; Steinberg, B; Christensen, B

    1992-01-01

    We used changes in regional cerebral blood flow (rCBF) to disclose regions involved in central auditory and language processing in the normal brain. rCBF was quantified with a fast-rotating, single-photon emission computerized tomograph (SPECT) and inhalation of 133Xe. rCBF data were obtained...... simultaneously from parallel, transverse slices of the brain. The lower slice was positioned to include both Broca's and Wernicke's areas. The upper slice included regions generally regarded by neurobehaviorists as less related to primary auditory or linguistic functions. We presented three types of auditory......'s area (left hemisphere), when subjects listened to narrative speech, compared to white noise (baseline). No significant rCBF differences were detected with this test during dichotic stimulation vs. white noise. A more sophisticated statistical method (factor analysis) disclosed patterns of functionally...

  10. Expression of the R2R3-MYB transcription factor TaMYB14 from Trifolium arvense activates proanthocyanidin biosynthesis in the legumes Trifolium repens and Medicago sativa.

    Science.gov (United States)

    Hancock, Kerry R; Collette, Vern; Fraser, Karl; Greig, Margaret; Xue, Hong; Richardson, Kim; Jones, Chris; Rasmussen, Susanne

    2012-07-01

    Proanthocyanidins (PAs) are oligomeric flavonoids and one group of end products of the phenylpropanoid pathway. PAs have been reported to be beneficial for human and animal health and are particularly important in pastoral agricultural systems for improved animal production and reduced greenhouse gas emissions. However, the main forage legumes grown in these systems, such as Trifolium repens and Medicago sativa, do not contain any substantial amounts of PAs in leaves. We have identified from the foliar PA-accumulating legume Trifolium arvense an R2R3-MYB transcription factor, TaMYB14, and provide evidence that this transcription factor is involved in the regulation of PA biosynthesis in legumes. TaMYB14 expression is necessary and sufficient to up-regulate late steps of the phenylpropanoid pathway and to induce PA biosynthesis. RNA interference silencing of TaMYB14 resulted in almost complete cessation of PA biosynthesis in T. arvense, whereas Nicotiana tabacum, M. sativa, and T. repens plants constitutively expressing TaMYB14 synthesized and accumulated PAs in leaves up to 1.8% dry matter. Targeted liquid chromatography-multistage tandem mass spectrometry analysis identified foliar PAs up to degree of polymerization 6 in leaf extracts. Hence, genetically modified M. sativa and T. repens plants expressing TaMYB14 provide a viable option for improving animal health and mitigating the negative environmental impacts of pastoral animal production systems.

  11. Factorizing twists and R-matrices for representations of the quantum affine algebra U_q(\\hat sl_2)

    OpenAIRE

    Pfeiffer, Hendryk

    2000-01-01

    We calculate factorizing twists in evaluation representations of the quantum affine algebra U_q(\\hat sl_2). From the factorizing twists we derive a representation independent expression of the R-matrices of U_q(\\hat sl_2). Comparing with the corresponding quantities for the Yangian Y(sl_2), it is shown that the U_q(\\hat sl_2) results can be obtained by `replacing numbers by q-numbers'. Conversely, the limit q -> 1 exists in representations of U_q(\\hat sl_2) and both the factorizing twists and...

  12. Alpha-1 proteinase inhibitor M358R reduces thrombin generation when displayed on the surface of cells expressing tissue factor.

    Science.gov (United States)

    Gierczak, Richard F; Pepler, Laura; Bhagirath, Vinai; Liaw, Patricia C; Sheffield, William P

    2014-11-01

    The M358R variant of alpha-1-proteinase inhibitor (API) is a potent soluble inhibitor of thrombin. Previously we engineered AR-API M358R, a membrane-bound form of this protein and showed that it inhibited exogenous thrombin when expressed on transfected cells lacking tissue factor (TF). To determine the suitability of AR-API M358R for gene transfer to vascular cells to limit thrombogenicity, we tested the ability of AR-API M358R to inhibit endogenous thrombin generated in plasma via co-expression co-expressing it on the surface of cells expressing TF. Transfected AR-API M358R formed inhibitory complexes with thrombin following exposure of recalcified, defibrinated plasma to TF on T24/83 cells, but discontinuously monitored thrombin generation was unaffected. Similarly, AR-API M358R expression did not reduce continuously monitored thrombin generation by T24/83 cell suspensions exposed to recalcified normal plasma in a Thrombogram-Thrombinoscope-type thrombin generation assay (TGA); in contrast, 1 μM hirudin variant 3 or soluble API M358R abolished thrombin generation. Gene transfer of TF to HEK 293 conferred the ability to support TF-dependent thrombin generation on HEK 293 cells. Co-transfection of HEK 293 cells with a 9:1 excess of DNA encoding AR-API M358R to that encoding TF reduced peak thrombin generation approximately 3-fold compared to controls. These in vitro results suggest that surface display of API M358R inhibits thrombin generation when the tethered serpin is expressed in excess of TF, and suggest its potential to limit thrombosis in appropriate vascular beds in animal models.

  13. Measurement of the {ovr {ital B}} {r_arrow} {ital Dl}{ovr {nu} } Partial Width and Form Factor Parameters

    Energy Technology Data Exchange (ETDEWEB)

    Athanas, M.; Avery, P.; Jones, C.D.; Lohner, M.; Prescott, C.; Yelton, J.; Zheng, J. [University of Florida, Gainesville, Florida 32611 (United States); Brandenburg, G.; Briere, R.A.; Ershov, A.; Gao, Y.S.; Kim, D.Y.; Wilson, R.; Yamamoto, H. [Harvard University, Cambridge, Massachusetts 02138 (United States); Browder, T.E.; Li, F.; Li, Y.; Rodriguez, J.L. [University of Hawaii at Manoa, Honolulu, Hawaii 96822 (United States); Bergfeld, T.; Eisenstein, B.I.; Ernst, J.; Gladding, G.E.; Gollin, G.D.; Hans, R.M.; Johnson, E.; Karliner, I.; Marsh, M.A.; Palmer, M.; Selen, M.; Thaler, J.J. [University of Illinois, Champaign-Urbana, Illinois 61801 (United States); Edwards, K.W.; Edwards, K.W. [the Institute of Particle Physics (Canada); Bellerive, A.; Bellerive, A.; Janicek, R.; Janicek, R.; MacFarlane, D.B.; MacFarlane, D.B.; Patel, P.M.; Patel, P.M. [the Institute of Particle Physics (Canada); Sadoff, A.J. [Ithaca College, Ithaca, New York 14850 (United States); Ammar, R.; Baringer, P.; Bean, A.; Besson, D.; Coppage, D.; Darling, C.; Davis, R.; Hancock, N.; Kotov, S.; Kravchenko, I.; Kwak, N. [University of Kansas, Lawrence, Kansas 66045 (United States); Anderson, S.; Kubota, Y.; Lee, S.J.; ONeill, J.J.; Patton, S.; Poling, R.; Riehle, T.; Savinov, V.; Smith, A. [University of Minnesota, Minneapolis, Minnesota 55455 (United States); Alam, M.S.; Athar, S.B.; Ling, Z.; Mahmood, A.H.; Severini, H.; Timm, S.; Wappler, F. [State University of New York at Albany, Albany, New York 12222 (United States); Anastassov, A.; Blinov, S.; Duboscq, J.E.; Fujino, D.; Gan, K.K.; Hart, T.; Honscheid, K.; Kagan, H.; Kass, R.; Lee, J.; Spencer, M.B.; Sung, M.; Undrus, A.; Wanke, R.; Wolf, A.; Zoeller, M.M. [Ohio State University, Columbus, Ohio 43210 (United States); Nemati, B.; Richichi, S.J.; Ross, W.R.; Skubic, P. [University of Oklahoma, Norman, Oklahoma 73019 (United States); Bishai, M.; Fast, J.; Gerndt, E.; Hinson, J.W.; Menon, N.; Miller, D.H.; Shibata, E.I.; and others

    1997-09-01

    We have studied the decay {bar B}{r_arrow}Dl{bar {nu}} , where l=e or {mu} . From a fit to the differential decay rate d{Gamma}/dw we measure the rate normalization F{sub D}(1){vert_bar}V{sub cb}{vert_bar} and form factor slope {cflx {rho}}{sup 2}{sub D} , and, using measured values of {tau}{sub B} , find {Gamma}({bar B}{r_arrow}Dl{bar {nu}}) = (12.0{plus_minus}0.9{plus_minus}2.1) ns{sup {minus}1}. The resulting branching fractions are B({bar B}{sup 0}{r_arrow}D{sup +}l{sup {minus}}{bar {nu}})=(1.87{plus_minus}0.15{plus_minus} 0.32){percent} and B(B{sup {minus}}{r_arrow}D{sup 0} l{sup {minus}}{bar {nu}})=(1.94{plus_minus}0.15{plus_minus}0.34){percent} . The form factor parameters are in agreement with those measured in {bar B}{r_arrow}D{sup *}l{bar {nu}} decays, as predicted by heavy quark effective theory. {copyright} {ital 1997} {ital The American Physical Society}

  14. RpoN Regulates Virulence Factors of Pseudomonas aeruginosa via Modulating the PqsR Quorum Sensing Regulator.

    Science.gov (United States)

    Cai, Zhao; Liu, Yang; Chen, Yicai; Yam, Joey Kuok Hoong; Chew, Su Chuen; Chua, Song Lin; Wang, Ke; Givskov, Michael; Yang, Liang

    2015-11-30

    The alternative sigma factor RpoN regulates many cell functions, such as motility, quorum sensing, and virulence in the opportunistic pathogen Pseudomonas aeruginosa (P. aeruginosa). P. aeruginosa often evolves rpoN-negative variants during the chronic infection in cystic fibrosis patients. It is unclear how RpoN interacts with other regulatory mechanisms to control virulence of P. aeruginosa. In this study, we show that RpoN modulates the function of PqsR, a quorum sensing receptor regulating production of virulence factors including the phenazine pyocyanin. The ∆rpoN mutant is able to synthesize 4-quinolone signal molecule HHQ but unable to activate PqsR and Pseudomonas quinolone signal (pqs) quorum sensing. The ∆rpoN mutant produces minimal level of pyocyanin and is unable to produce the anti-staphylococcal agents. Providing pqsR in trans in the ∆rpoN mutant restores its pqs quorum sensing and virulence factor production to the wild-type level. Our study provides evidence that RpoN has a regulatory effect on P. aeruginosa virulence through modulating the function of the PqsR quorum sensing regulator.

  15. RpoN Regulates Virulence Factors of Pseudomonas aeruginosa via Modulating the PqsR Quorum Sensing Regulator

    Directory of Open Access Journals (Sweden)

    Zhao Cai

    2015-11-01

    Full Text Available The alternative sigma factor RpoN regulates many cell functions, such as motility, quorum sensing, and virulence in the opportunistic pathogen Pseudomonas aeruginosa (P. aeruginosa. P. aeruginosa often evolves rpoN-negative variants during the chronic infection in cystic fibrosis patients. It is unclear how RpoN interacts with other regulatory mechanisms to control virulence of P. aeruginosa. In this study, we show that RpoN modulates the function of PqsR, a quorum sensing receptor regulating production of virulence factors including the phenazine pyocyanin. The ∆rpoN mutant is able to synthesize 4-quinolone signal molecule HHQ but unable to activate PqsR and Pseudomonas quinolone signal (pqs quorum sensing. The ∆rpoN mutant produces minimal level of pyocyanin and is unable to produce the anti-staphylococcal agents. Providing pqsR in trans in the ∆rpoN mutant restores its pqs quorum sensing and virulence factor production to the wild-type level. Our study provides evidence that RpoN has a regulatory effect on P. aeruginosa virulence through modulating the function of the PqsR quorum sensing regulator.

  16. Low energy R-matrix fits for the 6Li(d,a)4He S factor

    CERN Document Server

    Grineviciute, J; Lamia, L; Spitaleri, C; La Cognata, M

    2014-01-01

    Background: The information about the 6Li(d,a)4He reaction rates of the astrophysical interest can be obtained by extrapolating direct data to the lower energies, or by indirect methods. The indirect Trojan Horse method, as well as various R-matrix and polynomial fits to direct data, estimate the electron screening energies much larger than the adiabatic limit. Calculations that include the subthreshold resonance estimate smaller screening energies. Purpose: Obtain the 6Li(d,a)4He reaction R-matrix parameters and the astrophysical S factor for the energies relevant to the stellar plasmas by fitting the R-matrix formulas for the subthreshold resonances to the S factor data above 60 keV. Methods: The bare S factor is calculated using the single and the two-level R-matrix formulas for the closest to the threshold 0+ and 2+ subthreshold states at 22.2, 20.2 and 20.1 MeV. The electron screening potential Ue is then obtained by fitting it as a single parameter to the low energy data. Results: The low energy S facto...

  17. Structural Underpinnings of Nitrogen Regulation by the Prototypical Nitrogen-Responsive Transcriptional Factor NrpR

    Energy Technology Data Exchange (ETDEWEB)

    Wisedchaisri, Goragot; Dranow, David M.; Lie, Thomas J.; Bonanno, Jeffrey B.; Patskovsky, Yury; Ozyurt, Sinem A.; Sauder, J. Michael; Almo, Steven C.; Wasserman, Stephen R.; Burley, Stephen K.; Leigh, John A.; Gonen, Tamir (UWASH); (Einstein); (Lilly)

    2010-11-29

    Plants and microorganisms reduce environmental inorganic nitrogen to ammonium, which then enters various metabolic pathways solely via conversion of 2-oxoglutarate (2OG) to glutamate and glutamine. Cellular 2OG concentrations increase during nitrogen starvation. We recently identified a family of 2OG-sensing proteins - the nitrogen regulatory protein NrpR - that bind DNA and repress transcription of nitrogen assimilation genes. We used X-ray crystallography to determine the structure of NrpR regulatory domain. We identified the NrpR 2OG-binding cleft and show that residues predicted to interact directly with 2OG are conserved among diverse classes of 2OG-binding proteins. We show that high levels of 2OG inhibit NrpRs ability to bind DNA. Electron microscopy analyses document that NrpR adopts different quaternary structures in its inhibited 2OG-bound state compared with its active apo state. Our results indicate that upon 2OG release, NrpR repositions its DNA-binding domains correctly for optimal interaction with DNA thereby enabling gene repression.

  18. Regulation of root hair cell differentiation by R3 MYB transcription factors in tomato and Arabidopsis

    OpenAIRE

    Tominaga-Wada, Rumi; Wada, Takuji

    2014-01-01

    CAPRICE (CPC) encodes a small protein with an R3 MYB motif and regulates root hair and trichome cell differentiation in Arabidopsis thaliana. Six additional CPC-like MYB proteins including TRIPTYCHON (TRY), ENHANCER OF TRY AND CPC1 (ETC1), ENHANCER OF TRY AND CPC2 (ETC2), ENHANCER OF TRY AND CPC3/CPC-LIKE MYB3 (ETC3/CPL3), TRICHOMELESS1 (TCL1), and TRICHOMELESS2/CPC-LIKE MYB4 (TCL2/CPL4) also have the ability to regulate root hair and/or trichome cell differentiation in Arabidopsis. In this r...

  19. The microRNA miR-181c controls microglia-mediated neuronal apoptosis by suppressing tumor necrosis factor

    Directory of Open Access Journals (Sweden)

    Zhang Li

    2012-09-01

    Full Text Available Abstract Background Post-ischemic microglial activation may contribute to neuronal damage through the release of large amounts of pro-inflammatory cytokines and neurotoxic factors. The involvement of microRNAs (miRNAs in the pathogenesis of disorders related to the brain and central nervous system has been previously studied, but it remains unknown whether the production of pro-inflammatory cytokines is regulated by miRNAs. Methods BV-2 and primary rat microglial cells were activated by exposure to oxygen-glucose deprivation (OGD. Global cerebral ischemia was induced using the four-vessel occlusion (4-VO model in rats. Induction of pro-inflammatory and neurotoxic factors, such as tumor necrosis factor (TNF-α, interleukin (IL-1β, and nitric oxide (NO, were assessed by ELISA, immunofluorescence, and the Griess assay, respectively. The miRNA expression profiles of OGD-activated BV-2 cells were subsequently compared with the profiles of resting cells in a miRNA microarray. BV-2 and primary rat microglial cells were transfected with miR-181c to evaluate its effects on TNF-α production after OGD. In addition, a luciferase reporter assay was conducted to confirm whether TNF-α is a direct target of miR-181c. Results OGD induced BV-2 microglial activation in vitro, as indicated by the overproduction of TNF-α, IL-1β, and NO. Global cerebral ischemia/reperfusion injury induced microglial activation and the release of pro-inflammatory cytokines in the hippocampus. OGD also downregulated miR-181c expression and upregulated TNF-α expression. Overproduction of TNF-α after OGD-induced microglial activation provoked neuronal apoptosis, whereas the ectopic expression of miR-181c partially protected neurons from cell death caused by OGD-activated microglia. RNAinterference-mediated knockdown of TNF-α phenocopied the effect of miR-181c-mediated neuronal protection, whereas overexpression of TNF-α blocked the miR-181c-dependent suppression of apoptosis

  20. Arabidopsis ABA Receptor RCAR1/PYL9 Interacts with an R2R3-Type MYB Transcription Factor, AtMYB44

    Directory of Open Access Journals (Sweden)

    Dekuan Li

    2014-05-01

    Full Text Available Abscisic acid (ABA signaling plays important roles in plant growth, development and adaptation to various stresses. RCAR1/PYL9 has been known as a cytoplasm and nuclear ABA receptor in Arabidopsis. To obtain further insight into the regulatory mechanism of RCAR1/PYL9, a yeast two-hybrid approach was performed to screen for RCAR1/PYL9-interacting proteins and an R2R3-type MYB transcription factor, AtMYB44, was identified. The interaction between RCAR1/PYL9 and AtMYB44 was further confirmed by glutathione S-transferase (GST pull-down and bimolecular fluorescence complementation (BiFC assays. Gene expression analysis showed that AtMYB44 negatively regulated the expression of ABA-responsive gene RAB18, in contrast to the opposite role reported for RCAR1/PYL9. Competitive GST pull-down assay and analysis of phosphatase activity demonstrated that AtMYB44 and ABI1 competed for binding to RCAR1/PYL9 and thereby reduced the inhibitory effect of RCAR1/PYL9 on ABI1 phosphatase activity in the presence of ABA in vitro. Furthermore, transient activation assay in protoplasts revealed AtMYB44 probably also decreased RCAR1/PYL9-mediated inhibition of ABI1 activity in vivo. Taken together, our work provides a reasonable molecular mechanism of AtMYB44 in ABA signaling.

  1. Isolation of a novel MYB transcription factor OsMyb1R from rice and ...

    African Journals Online (AJOL)

    Yomi

    2012-02-23

    Feb 23, 2012 ... sterilized with 0.1% HgCl2 for 10 min, water washing 3 times, seeds soaking was done for .... dividing point of OsMyb1R relative expression level was the same as .... tolerance to freezing, drought, and salt stress in transgenic.

  2. [Studies on expression, purification, crystal growth and optimization of putative transcription factor LytR from Streptococcus pneumoniae].

    Science.gov (United States)

    Min, Xun; Zhong, Wen; Zhao, Shasha; Dong, Jie; Dong, Shanshan; Zhou, Aie; Yan, Wenjuan; Wang, Deqiang

    2013-08-01

    The aim of the present study was to obtain the crystal of transcription factor LytR of streptococcus pneumoniae for X-ray crystal structure and function analysis. The LytR gene of D39 strains from Streptococcus pneumoniae (S. pn) was cloned into the prokaryotic expression vector pET32a(+), then overexpression was obtained in the E. coli BL21 (DE3) through transformation of the recombinant plasmid that had been verified by colony PCR and sequencing. Soluble fusion protein with His-tag highly expressed by the induction of 0.5 mmol/L IPTG and was purified by a three step procedure, the purity of the purified LytR recombinant protein was over 90%. Preliminary screening of crystallization conditions was performed using the hanging-drop vapour-diffusing method with Hampton Crystal screen and PEG screen kits. The protein crystals X-ray diffraction data were collected from a single crystal and more stick crystals whose X-ray diffraction reached 4.0 A were obtained. These works laid the foundation for further research on the 3D structure of putative transcription factor LytR and its biological aspects.

  3. Therapeutic and routine prophylactic properties of rFactor VIII Fc (efraloctocog alfa, Eloctate®) in hemophilia A

    Science.gov (United States)

    Chowdary, Pratima; Fosbury, Emma; Riddell, Anne; Mathias, Mary

    2016-01-01

    rFVIIIFc (efraloctocog alfa, Eloctate®) is an extended half-life (EHL) factor VIII licensed for use in patients with hemophilia A for prophylaxis and treatment of bleeding and surgical episodes. Pharmacokinetic studies in adults have shown a mean 1.5-fold increase in half-life compared to full-length factor VIII. When compared to adults, the half-life is decreased by 8% in adolescents between 12 and 17 years, by 18% in children 6 to <12 years, and by 33% in children between the ages of 2 and <6 years. There is a considerable interindividual variation in the prolongation of the half-life particularly in children and across the age groups, the range extending from no increase to a 2.5-fold increase. In addition to age, von willebrand factor (VWF) antigen level has demonstrated a significant impact on rFVIIIFc half-life, with higher VWF levels associated with greater prolongation of half-life. The pivotal and pediatric clinical trials have demonstrated the efficacy and safety of rFVIIIFc for use in regular prophylaxis and in management of bleeds and surgery. In these studies, just under half the participants showed a zero annualized bleed rate (ABR), and the median ABR (1.6 in the pivotal study for the individualized prophylaxis arm) showed a further decrease in the extension study. On average, the patients required fewer infusions (reduced by at least a third), and the mean weekly consumption seems to be in keeping with standard recombinant factor VIII. EHL rFVIIIFc has made decreased infusion frequency a possibility. However, the interindividual variability in dose and infusion frequency highlights the need for a personalized approach based on individual patient’s half-life and/or response to treatment. PMID:27695377

  4. Purification, crystallization and X-ray crystallographic studies of a Bacillus cereus MepR-like transcription factor, BC0657.

    Science.gov (United States)

    Cho, Min Uk; Kim, Meong Il; Hong, Minsun

    2015-06-01

    Transcription factors of the MarR family respond to internal and external changes and regulate a variety of biological functions through ligand association with microorganisms. MepR belongs to the MarR family, and its mutations are associated with the development of multidrug resistance in Staphylococcus aureus, which has caused a growing health problem. In this study, a Bacillus cereus MepR-like transcription regulator, BC0657, was crystallized. The BC0657 crystals diffracted to 2.05 Å resolution and belonged to either space group P6(2)22 or P6(4)22, with unit-cell parameters a = 110.57, b = 110.57, c = 67.29 Å. There was one molecule per asymmetric unit. Future comparative structural studies on BC0657 would extend knowledge of ligand-induced transcriptional regulatory mechanisms in the MarR family and would make a significant contribution to the design of antibiotic drugs against multidrug-resistant bacteria.

  5. Biophysical analysis of MarR family transcription factors from Streptomyces coelicolor

    OpenAIRE

    Holley, Tracey

    2012-01-01

    Streptomycetes represent a rich source of potentially useful therapeutics. However, in a laboratory environment, a large proportion of their secondary metabolite gene clusters remain silent, and thus their full metabolic potential is not realised. One way to unlock these so-called "cryptic" clusters may be to manipulate specific regulatory proteins. But, the vast majority of these regulators are uncharacterized, making it difficult to do this in a rational way. The MarR family of regulatory p...

  6. The network structure of human personality according to the NEO-PI-R: matching network community structure to factor structure.

    Directory of Open Access Journals (Sweden)

    Rutger Goekoop

    Full Text Available INTRODUCTION: Human personality is described preferentially in terms of factors (dimensions found using factor analysis. An alternative and highly related method is network analysis, which may have several advantages over factor analytic methods. AIM: To directly compare the ability of network community detection (NCD and principal component factor analysis (PCA to examine modularity in multidimensional datasets such as the neuroticism-extraversion-openness personality inventory revised (NEO-PI-R. METHODS: 434 healthy subjects were tested on the NEO-PI-R. PCA was performed to extract factor structures (FS of the current dataset using both item scores and facet scores. Correlational network graphs were constructed from univariate correlation matrices of interactions between both items and facets. These networks were pruned in a link-by-link fashion while calculating the network community structure (NCS of each resulting network using the Wakita Tsurumi clustering algorithm. NCSs were matched against FS and networks of best matches were kept for further analysis. RESULTS: At facet level, NCS showed a best match (96.2% with a 'confirmatory' 5-FS. At item level, NCS showed a best match (80% with the standard 5-FS and involved a total of 6 network clusters. Lesser matches were found with 'confirmatory' 5-FS and 'exploratory' 6-FS of the current dataset. Network analysis did not identify facets as a separate level of organization in between items and clusters. A small-world network structure was found in both item- and facet level networks. CONCLUSION: We present the first optimized network graph of personality traits according to the NEO-PI-R: a 'Personality Web'. Such a web may represent the possible routes that subjects can take during personality development. NCD outperforms PCA by producing plausible modularity at item level in non-standard datasets, and can identify the key roles of individual items and clusters in the network.

  7. RIEDEL MEGASHEARS R' AND THE TREND TO GRAVITATIONAL EQUILIBRIUM AS MAIN FACTORS OF TSUNAMIGENIC EARTHQUAKES

    Directory of Open Access Journals (Sweden)

    M. A. Goncharov

    2015-09-01

    Full Text Available An earthquake source is characterized by two nodal planes oriented parallel to two planes of maximum shear stresses (Fig. 1, left. A rapid displacement of the shear type (in mechanical, rather than in the geological meaning occurs along one of the planes and causes an earthquake.The concept of plate tectonics with one of its main components, subduction zones, provides, at first sight, the unique opportunity to select one of the two nodal planes – a gently dipping plane which is parallel to the roof of the subducting oceanic plate (Fig. 1, bottom right. The other nodal plane that is steeply dipping in the opposite direction (Fig. 1, top right seems ‘unpromising’, considering the aspect of seismicity, for two reasons. First, displacement along this plate is contrary to the general direction of oceanic plate subduction. Secondly, such displacement is directed against the direction of gravity, which is energetically disadvantageous.However, it should be taken into account that in the stress field of the subduction zone, as in any stress field, the two above-mentioned maximum shear stresses have equal values. At the same time, it is the sub-vertical displacement that excites rapid uplifting of the seabed which causes a tsunami. Researchers who support the traditional choice of a gently dipping nodal plane have to reckon with it and therefore create complex models, such as the ‘splay fault’ model that seem most successful, though being quite complicated and controversial (Figs. 56 and 57.In our opinion, the geological reality is more adequately refelected by the geological and geophysical model shown in Fig. 1 (right. It is based on the wide range of information and assumes that both nodal planes are equivalent and interchange in generation of strong earthquakes.The aim of this article is to consider this model in terms of tectonophysics. For this purpose, earthquake sources indicated on (Fig. 1, right are classified as Riedel megashears, R

  8. Fibroblast growth factor (Fgf) 21 is a novel target gene of the aryl hydrocarbon receptor (AhR)

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Xingguo, E-mail: chengx@stjohns.edu [Department of Pharmaceutical Sciences, St. John' s University, 8000 Utopia Parkway, Queens, NY 11439 (United States); Vispute, Saurabh G. [Department of Pharmaceutical Sciences, St. John' s University, 8000 Utopia Parkway, Queens, NY 11439 (United States); Liu, Jie [Department of Internal Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160 (United States); Cheng, Christine; Kharitonenkov, Alexei [Lilly Research Laboratories, Division of Eli Lilly and Co., Indianapolis, IN 46285 (United States); Klaassen, Curtis D., E-mail: curtisklaassenphd@gmail.com [Department of Internal Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160 (United States)

    2014-07-01

    The toxic effects of dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), mainly through activation of the aryl hydrocarbon receptor (AhR) are well documented. Fibroblast growth factor (Fgf) 21 plays critical roles in metabolic adaptation to fasting by increasing lipid oxidation and ketogenesis in the liver. The present study was performed to determine whether activation of the AhR induces Fgf21 expression. In mouse liver, TCDD increased Fgf21 mRNA in both dose- and time-dependent manners. In addition, TCDD markedly increased Fgf21 mRNA expression in cultured mouse and human hepatocytes. Moreover, TCDD increased mRNA (in liver) and protein levels (in both liver and serum) of Fgf21 in wild-type mice, but not in AhR-null mice. Chromatin immunoprecipitation assays showed that TCDD increased AhR protein binding to the Fgf21 promoter (− 105/+ 1 base pair). Fgf21-null mice administered 200 μg/kg of TCDD died within 20 days, whereas wild-type mice receiving the same treatment were still alive at one month after administration. This indicates that TCDD-induced Fgf21 expression protects against TCDD toxicity. Diethylhexylphthalate (DEHP) pretreatment attenuated TCDD-induced Fgf21 expression in mouse liver and white adipose tissue, which may explain a previous report that DEHP pretreatment decreases TCDD-induced wasting. In conclusion, Fgf21 appears to be a target gene of AhR-signaling pathway in mouse and human liver. - Highlights: • TCDD induced Fgf21 expression at both mRNA and protein levels. • Fgf21 induction by TCDD is AhR-dependent. • DEHP attenuated TCDD-induced Fgf21 expression.

  9. The potato developer (D) locus encodes an R2R3 MYB transcription factor that regulates expression of multiple anthocyanin structural genes in tuber skin.

    Science.gov (United States)

    Jung, Chun Suk; Griffiths, Helen M; De Jong, Darlene M; Cheng, Shuping; Bodis, Mary; Kim, Tae Sung; De Jong, Walter S

    2009-12-01

    A dominant allele at the D locus (also known as I in diploid potato) is required for the synthesis of red and purple anthocyanin pigments in tuber skin. It has previously been reported that D maps to a region of chromosome 10 that harbors one or more homologs of Petunia an2, an R2R3 MYB transcription factor that coordinately regulates the expression of multiple anthocyanin biosynthetic genes in the floral limb. To test whether D acts similarly in tuber skin, RT-PCR was used to evaluate the expression of flavanone 3-hydroxylase (f3h), dihydroflavonol 4-reductase (dfr) and flavonoid 3',5'-hydroxylase (f3'5'h). All three genes were expressed in the periderm of red- and purple-skinned clones, while dfr and f3'5'h were not expressed, and f3h was only weakly expressed, in white-skinned clones. A potato cDNA clone with similarity to an2 was isolated from an expression library prepared from red tuber skin, and an assay developed to distinguish the two alleles of this gene in a diploid potato clone known to be heterozygous Dd. One allele was observed to cosegregate with pigmented skin in an F(1) population of 136 individuals. This allele was expressed in tuber skin of red- and purple-colored progeny, but not in white tubers, while other parental alleles were not expressed in white or colored tubers. The allele was placed under the control of a doubled 35S promoter and transformed into the light red-colored cultivar Désirée, the white-skinned cultivar Bintje, and two white diploid clones known to lack the functional allele of D. Transformants accumulated pigment in tuber skin, as well as in other tissues, including young foliage, flower petals, and tuber flesh.

  10. Platelet-activating factor receptor (PAF-R-dependent pathways control tumour growth and tumour response to chemotherapy

    Directory of Open Access Journals (Sweden)

    Rohde Ciro BS

    2010-05-01

    Full Text Available Abstract Background Phagocytosis of apoptotic cells by macrophages induces a suppressor phenotype. Previous data from our group suggested that this occurs via Platelet-activating factor receptor (PAF-R-mediated pathways. In the present study, we investigated the impact of apoptotic cell inoculation or induction by a chemotherapeutic agent (dacarbazine, DTIC on tumour growth, microenvironmental parameters and survival, and the effect of treatment with a PAF-R antagonist (WEB2170. These studies were performed in murine tumours: Ehrlich Ascitis Tumour (EAT and B16F10 melanoma. Methods Tumour growth was assessed by direct counting of EAT cells in the ascitis or by measuring the volume of the solid tumour. Parameters of the tumour microenvironment, such as the frequency of cells expressing cyclo-oxygenase-2 (COX-2, caspase-3 and galectin-3, and microvascular density, were determined by immunohistochemistry. Levels of vascular endothelium growth factor (VEGF and prostaglandin E2 (PGE2 were determined by ELISA, and levels of nitric oxide (NO by Griess reaction. PAF-R expression was analysed by immunohistochemistry and flow cytometry. Results Inoculation of apoptotic cells before EAT implantation stimulated tumour growth. This effect was reversed by in vivo pre-treatment with WEB2170. This treatment also reduced tumour growth and modified the microenvironment by reducing PGE2, VEGF and NO production. In B16F10 melanoma, WEB2170 alone or in association with DTIC significantly reduced tumour volume. Survival of the tumour-bearing mice was not affected by WEB2170 treatment but was significantly improved by the combination of DTIC with WEB2170. Tumour microenvironment elements were among the targets of the combination therapy since the relative frequency of COX-2 and galectin-3 positive cells and the microvascular density within the tumour mass were significantly reduced by treatment with WEB2170 or DTIC alone or in combination. Antibodies to PAF-R stained

  11. VizieR Online Data Catalog: Coupling factors of 5166 KIC (Mosser+, 2017)

    Science.gov (United States)

    Mosser, B.; Pincon, C.; Belkacem, K.; Takata, M.; Vrard, M.

    2017-08-01

    Seismic global parameters of the stars listed in the paper. Each star is identified with its KIC number (Kepler Input Catalog). Coupling factors of mixed modes were measured for thousands of red giants. They show specific variation with mass and evolutionary stage. Weak coupling is observed for the most evolved stars on the red giant branch only; large coupling factors are measured at the transition between subgiants and red giants as well as in the red clump. Period spacings and evolutionary stages are from Vrard et (2016, Cat. J/A+A/588/A87). (1 data file).

  12. R497K polymorphism in epidermal growth factor receptor gene is associated with the risk of acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Pan Xin-Min

    2008-07-01

    Full Text Available Abstract Background Previous studies suggested that genetic polymorphisms in the epidermal growth factor receptor (EGFR gene had been implicated in the susceptibility to some tumors and inflammatory diseases. EGFR has been recently implicated in vascular pathophysiological processes associated with excessive remodeling and atherosclerosis. Acute coronary syndrome (ACS is a clinical manifestation of preceding atherosclerosis. Our purpose was to investigate the association of the EGFR polymorphism with the risk of ACS. In this context, we analyzed the HER-1 R497K and EGFR intron 1 (CAn repeat polymorphisms in 191 patients with ACS and 210 age- and sex-matched controls in a Chinese population, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP strategy and direct sequencing. Results There were significant differences in the genotype and allele distribution of R497K polymorphism of the EGFR gene between cases and controls. The Lys allele had a significantly increased risk of ACS compared with the Arg allele (adjusted OR = 1.49, 95% CI: 1.12–1.98, adjusted P = 0.006. However, no significant relationship between the number of (CAn repeats of EGFR intron 1 (both alleles P = 0.911. Considering these two polymorphisms together, there was no statistically significant difference between the two groups. Conclusion R497K polymorphism of the EGFR gene is significantly associated with the risk of ACS. Our data suggests that R497K polymorphism may be used as a genetic susceptibility marker of the ACS.

  13. Targeting of the human coagulation factor IX gene at rDNA locus of human embryonic stem cells.

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    Xionghao Liu

    Full Text Available BACKGROUND: Genetic modification is a prerequisite to realizing the full potential of human embryonic stem cells (hESCs in human genetic research and regenerative medicine. Unfortunately, the random integration methods that have been the primary techniques used keep creating problems, and the primary alternative method, gene targeting, has been effective in manipulating mouse embryonic stem cells (mESCs but poorly in hESCs. METHODOLOGY/PRINCIPAL FINDINGS: Human ribosomal DNA (rDNA repeats are clustered on the short arm of acrocentric chromosomes. They consist of approximately 400 copies of the 45S pre-RNA (rRNA gene per haploid. In the present study, we targeted a physiological gene, human coagulation factor IX, into the rDNA locus of hESCs via homologous recombination. The relative gene targeting efficiency (>50% and homologous recombination frequency (>10(-5 were more than 10-fold higher than those of loci targeted in previous reports. Meanwhile, the targeted clones retained both a normal karyotype and the main characteristics of ES cells. The transgene was found to be stably and ectopically expressed in targeted hESCs. CONCLUSION/SIGNIFICANCE: This is the first targeting of a human physiological gene at a defined locus on the hESC genome. Our findings indicate that the rDNA locus may serve as an ideal harbor for transgenes in hESCs.

  14. BotR/A and TetR are alternative RNA polymerase sigma factors controlling the expression of the neurotoxin and associated protein genes in Clostridium botulinum type A and Clostridium tetani.

    Science.gov (United States)

    Raffestin, Stéphanie; Dupuy, Bruno; Marvaud, Jean Christophe; Popoff, Michel R

    2005-01-01

    Clostridium botulinum and Clostridium tetani, respectively, produce potent toxins, botulinum neurotoxin (BoNT) and tetanus neurotoxin (TeTx), which are responsible for severe diseases, botulism and tetanus. Neurotoxin synthesis is a regulated process in Clostridium. The genes botR/A in C. botulinum A and tetR in C. tetani positively regulate expression of BoNT/A and associated non-toxic proteins (ANTPs), as well as TeTx respectively. The botR/A gene lies in close vicinity of the two operons which contain bont/A and antps genes in C. botulinum A, and tetR immediately precedes the tetX gene in C. tetani. We show that BotR/A and TetR function as specific alternative sigma factors rather than positive regulators based on the following results: (i) BotR/A and TetR associated with target DNAs only in the presence of the RNA polymerase core enzyme (Core), (ii) BotR/A and TetR directly bound with the core enzyme, (iii) BotR/A-Core recognized -35 and -10 regions of ntnh-bont/A promoter and (iv) BotR/A and TetR triggered in vitro transcription from the target promoters. In C. botulinum A, bont/A and antps genes are transcribed as bi- and tricistronic operons controlled by BotR/A. BotR/A and TetR are seemingly related to a new subgroup of the sigma70 family that includes TcdR and UviA, which, respectively, regulate production of toxins A and B in C. difficile and bacteriocin in C. perfringens. Sequences of -35 region are highly conserved in the promoter of target toxin genes in C. botulinum, C. tetani, C. difficile and C. perfringens. Overall, a common regulation mechanism probably controls toxin gene expression in these four toxigenic clostridial species.

  15. Hypothyroxinemia and TPO-antibody positivity are risk factors for premature delivery: the generation R study

    NARCIS (Netherlands)

    Korevaar, T.I.; Schalekamp-Timmermans, S.; Rijke, Y.B. de; Visser, W.E.; Visser, W. de; Keizer-Schrama, S.M.; Hofman, A.; Ross, H.A.; Hooijkaas, H.; Tiemeier, H.; Bongers-Schokking, J.J.; Jaddoe, V.W.; Visser, T.J.; Steegers, E.A.P.; Medici, M.; Peeters, R.P.

    2013-01-01

    CONTEXT: Premature delivery is an important risk factor for child mortality and psychiatric, metabolic, and cardiovascular disease later in life. In the majority of cases, the cause of prematurity cannot be identified. Currently, it remains controversial whether abnormal maternal thyroid function du

  16. Hypothyroxinemia and TPO-antibody positivity are risk factors for premature delivery: the generation R study

    NARCIS (Netherlands)

    Korevaar, T.I.; Schalekamp-Timmermans, S.; Rijke, Y.B. de; Visser, W.E.; Visser, W. de; Keizer-Schrama, S.M.; Hofman, A.; Ross, H.A.; Hooijkaas, H.; Tiemeier, H.; Bongers-Schokking, J.J.; Jaddoe, V.W.; Visser, T.J.; Steegers, E.A.P.; Medici, M.; Peeters, R.P.

    2013-01-01

    CONTEXT: Premature delivery is an important risk factor for child mortality and psychiatric, metabolic, and cardiovascular disease later in life. In the majority of cases, the cause of prematurity cannot be identified. Currently, it remains controversial whether abnormal maternal thyroid function

  17. Diversity of 16S rDNA and environmental factor influencing microorganisms in Malan ice core

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The research on extrempholic microorganisms in glacial low-temperature environment receives more attention than ever before. Due to the successive chronological records in ice core, it is important to initiate microbiological studies on ice core samples. 23 samples from one ice core, drilled from central Qinghai-Tibetan Plateau, were analyzed. The number of total microorganisms and culturable microorganisms in different layers showed that it related with the content of dust in ice. It is suggested that the distribution of microorganisms in ice depends on the transportation of materials during glacier development. The bacteria diversity in Malan Glacier was analyzed by 16S rDNA sequencing methods, which showed that many sequences were similar to known psychrophilic bacteria.

  18. Regulation of rDNA transcription in response to growth factors, nutrients and energy.

    Science.gov (United States)

    Kusnadi, Eric P; Hannan, Katherine M; Hicks, Rodney J; Hannan, Ross D; Pearson, Richard B; Kang, Jian

    2015-02-01

    Exquisite control of ribosome biogenesis is fundamental for the maintenance of cellular growth and proliferation. Importantly, synthesis of ribosomal RNA by RNA polymerase I is a key regulatory step in ribosome biogenesis and a major biosynthetic and energy consuming process. Consequently, ribosomal RNA gene transcription is tightly coupled to the availability of growth factors, nutrients and energy. Thus cells have developed an intricate sensing network to monitor the cellular environment and modulate ribosomal DNA transcription accordingly. Critical controllers in these sensing networks, which mediate growth factor activation of ribosomal DNA transcription, include the PI3K/AKT/mTORC1, RAS/RAF/ERK pathways and MYC transcription factor. mTORC1 also responds to amino acids and energy status, making it a key hub linking all three stimuli to the regulation of ribosomal DNA transcription, although this is achieved via overlapping and distinct mechanisms. This review outlines the current knowledge of how cells respond to environmental cues to control ribosomal RNA synthesis. We also highlight the critical points within this network that are providing new therapeutic opportunities for treating cancers through modulation of RNA polymerase I activity and potential novel imaging strategies.

  19. The Sinorhizobium meliloti LysR family transcriptional factor LsrB is involved in regulation of glutathione biosynthesis.

    Science.gov (United States)

    Lu, Dawei; Tang, Guirong; Wang, Dong; Luo, Li

    2013-10-01

    Glutathione, a key antioxidant in Sinorhizobium meliloti, is required for the development of alfalfa (Medicago sativa) nitrogen-fixing nodules. This tripeptide can be synthesized by both γ-glutamyl cysteine synthetase (GshA) and glutathione synthetase (GshB) in Escherichia coli and S. meliloti. Genetic evidence has indicated that the null mutant of S. meliloti gshA or gshB1 does not establish efficient symbiosis on alfalfa. However, the transcriptional regulation of gshA and gshB has not been well understood. Here, S. meliloti LsrB, a member of LysR family transcriptional factors, was found to positively regulate glutathione biosynthesis by activating the transcription of gshA and gshB1 under both free-living and symbiotic conditions. The decrease in glutathione production in the lsrB in-frame deletion mutant (lsrB1-2) was determined by using quadrupole time-of-flight liquid chromatography-mass spectrometry. The expression of gshA and gshB1 was correspondingly reduced in the mutant under free-living and symbiotic conditions by analyses of real-time quantitative reverse transcription-polymerase chain reaction and promoter-GUS fusions. Interestingly, LsrB positively regulated the transcription of oxyR, which encodes another member of LysR family regulators and responds to oxidative stresses in S. meliloti. The oxyR null mutant produced less glutathione, in which the transcription of gshA was consistently down-regulated. These findings demonstrate that glutathione biosynthesis is positively regulated by both LsrB and OxyR in S. meliloti.

  20. Fibroblast growth factor (Fgf) 21 is a novel target gene of the aryl hydrocarbon receptor (AhR).

    Science.gov (United States)

    Cheng, Xingguo; Vispute, Saurabh G; Liu, Jie; Cheng, Christine; Kharitonenkov, Alexei; Klaassen, Curtis D

    2014-07-01

    The toxic effects of dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), mainly through activation of the aryl hydrocarbon receptor (AhR) are well documented. Fibroblast growth factor (Fgf) 21 plays critical roles in metabolic adaptation to fasting by increasing lipid oxidation and ketogenesis in the liver. The present study was performed to determine whether activation of the AhR induces Fgf21 expression. In mouse liver, TCDD increased Fgf21 mRNA in both dose- and time-dependent manners. In addition, TCDD markedly increased Fgf21 mRNA expression in cultured mouse and human hepatocytes. Moreover, TCDD increased mRNA (in liver) and protein levels (in both liver and serum) of Fgf21 in wild-type mice, but not in AhR-null mice. Chromatin immunoprecipitation assays showed that TCDD increased AhR protein binding to the Fgf21 promoter (-105/+1 base pair). Fgf21-null mice administered 200μg/kg of TCDD died within 20days, whereas wild-type mice receiving the same treatment were still alive at one month after administration. This indicates that TCDD-induced Fgf21 expression protects against TCDD toxicity. Diethylhexylphthalate (DEHP) pretreatment attenuated TCDD-induced Fgf21 expression in mouse liver and white adipose tissue, which may explain a previous report that DEHP pretreatment decreases TCDD-induced wasting. In conclusion, Fgf21 appears to be a target gene of AhR-signaling pathway in mouse and human liver.

  1. Direct Regulation of rRNA Transcription by Fibroblast Growth Factor 2

    OpenAIRE

    Sheng, Zhi; Liang, Yanping; Lin, Chih-Yin; Comai, Lucio; Chirico, William J

    2005-01-01

    Fibroblast growth factor 2 (FGF-2), which is highly expressed in developing tissues and malignant cells, regulates cell growth, differentiation, and migration. Five isoforms (18 to ∼34 kDa) of FGF-2 are derived from alternative initiation codons of a single mRNA. The 18-kDa FGF-2 isoform is released from cells by a nonclassical secretory pathway and regulates gene expression by binding to cell surface receptors. This isoform also localizes to the nucleolus, raising the possibility that it may...

  2. Tucker3 method in biometrical research: Analysis of experiments with three factors, using R

    Science.gov (United States)

    de Araújo, Lúcio B.; Oliveira, Manuela M.; Dias, Carlos Tadeu dos S.; Oliveira, Amílcar; Oliveira, Teresa A.

    2012-09-01

    The present work aims to propose a systematic study and interpretation of a variable response in relation to three factors, using a model of Joint Table Analysis, the Tucker3 model, as well as the joint biplot graph. The proposed method seems efficient and suitable for separating standard technical response, and the pattern of noise contained in a three inputs table, as well as allows its interpretation. The joint plot graph facilitates the study and interpretation of the data structure and provides additional information on these. In our application the aim is to identify the combinations of genotypes, locations and years that contribute or not to a high yield of bean cultivars.

  3. Computational modeling of the bHLH domain of the transcription factor TWIST1 and R118C, S144R and K145E mutants

    Directory of Open Access Journals (Sweden)

    Maia Amanda M

    2012-07-01

    Full Text Available Abstract Background Human TWIST1 is a highly conserved member of the regulatory basic helix-loop-helix (bHLH transcription factors. TWIST1 forms homo- or heterodimers with E-box proteins, such as E2A (isoforms E12 and E47, MYOD and HAND2. Haploinsufficiency germ-line mutations of the twist1 gene in humans are the main cause of Saethre-Chotzen syndrome (SCS, which is characterized by limb abnormalities and premature fusion of cranial sutures. Because of the importance of TWIST1 in the regulation of embryonic development and its relationship with SCS, along with the lack of an experimentally solved 3D structure, we performed comparative modeling for the TWIST1 bHLH region arranged into wild-type homodimers and heterodimers with E47. In addition, three mutations that promote DNA binding failure (R118C, S144R and K145E were studied on the TWIST1 monomer. We also explored the behavior of the mutant forms in aqueous solution using molecular dynamics (MD simulations, focusing on the structural changes of the wild-type versus mutant dimers. Results The solvent-accessible surface area of the homodimers was smaller on wild-type dimers, which indicates that the cleft between the monomers remained more open on the mutant homodimers. RMSD and RMSF analyses indicated that mutated dimers presented values that were higher than those for the wild-type dimers. For a more careful investigation, the monomer was subdivided into four regions: basic, helix I, loop and helix II. The basic domain presented a higher flexibility in all of the parameters that were analyzed, and the mutant dimer basic domains presented values that were higher than the wild-type dimers. The essential dynamic analysis also indicated a higher collective motion for the basic domain. Conclusions Our results suggest the mutations studied turned the dimers into more unstable structures with a wider cleft, which may be a reason for the loss of DNA binding capacity observed for in vitro

  4. Expression, purification and preliminary X-ray diffraction studies of the transcriptional factor PyrR from Bacillus halodurans

    Energy Technology Data Exchange (ETDEWEB)

    Arreola, Rodrigo [Departamento de Bioquímica, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, Apartado Postal 70-243, Mexico City 04510 (Mexico); Vega-Miranda, Anita [Instituto Nacional de Enfermedades Respiratorias, Calzada de Tlalpan 4502, México DF 14080 (Mexico); Gómez-Puyou, Armando; Pérez-Montfort, Ruy [Departamento de Bioquímica, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, Apartado Postal 70-243, Mexico City 04510 (Mexico); Merino-Pérez, Enrique [Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Apartado Postal 510-3, Cuernavaca, Morelos (Mexico); Torres-Larios, Alfredo, E-mail: torres@ifc.unam.mx [Departamento de Bioquímica, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n, Ciudad Universitaria, Apartado Postal 70-243, Mexico City 04510 (Mexico)

    2008-08-01

    The gene-regulation factor PyrR from B. halodurans has been crystallized in two crystal forms. Preliminary crystallographic analysis showed that the protein forms tetramers in both space groups. The PyrR transcriptional regulator is widely distributed in bacteria. This RNA-binding protein is involved in the control of genes involved in pyrimidine biosynthesis, in which uridyl and guanyl nucleotides function as effectors. Here, the crystallization and preliminary X-ray diffraction analysis of two crystal forms of Bacillus halodurans PyrR are reported. One of the forms belongs to the monoclinic space group P2{sub 1} with unit-cell parameters a = 59.7, b = 87.4, c = 72.1 Å, β = 104.4°, while the other form belongs to the orthorhombic space group P22{sub 1}2{sub 1} with unit-cell parameters a = 72.7, b = 95.9, c = 177.1 Å. Preliminary X-ray diffraction data analysis and molecular-replacement solution revealed the presence of four and six monomers per asymmetric unit; a crystallographic tetramer is formed in both forms.

  5. The spliceosome U2 snRNP factors promote genome stability through distinct mechanisms; transcription of repair factors and R-loop processing.

    Science.gov (United States)

    Tanikawa, M; Sanjiv, K; Helleday, T; Herr, P; Mortusewicz, O

    2016-12-19

    Recent whole-exome sequencing of malignancies have detected recurrent somatic mutations in U2 small nuclear ribonucleoprotein complex (snRNP) components of the spliceosome. These factors have also been identified as novel players in the DNA-damage response (DDR) in several genome-wide screens and proteomic analysis. Although accumulating evidence implies that the spliceosome has an important role in genome stability and is an emerging hallmark of cancer, its precise role in DNA repair still remains elusive. Here we identify two distinct mechanisms of how spliceosome U2 snRNP factors contribute to genome stability. We show that the spliceosome maintains protein levels of essential repair factors, thus contributing to homologous recombination repair. In addition, real-time laser microirradiation analysis identified rapid recruitment of the U2 snRNP factor SNRPA1 to DNA-damage sites. Functional analysis of SNRPA1 revealed a more immediate and direct role in preventing R-loop-induced DNA damage. Our present study implies a complex interrelation between transcription, mRNA splicing and the DDR. Cells require rapid spatio-temporal coordination of these chromatin transactions to cope with various forms of genotoxic stress.

  6. The solution configurations of inactive and activated DntR have implications for the sliding dimer mechanism of LysR transcription factors.

    Science.gov (United States)

    Lerche, Michael; Dian, Cyril; Round, Adam; Lönneborg, Rosa; Brzezinski, Peter; Leonard, Gordon A

    2016-01-28

    LysR Type Transcriptional Regulators (LTTRs) regulate basic metabolic pathways or virulence gene expression in prokaryotes. Evidence suggests that the activation of LTTRs involves a conformational change from an inactive compact apo- configuration that represses transcription to an active, expanded holo- form that promotes it. However, no LTTR has yet been observed to adopt both configurations. Here, we report the results of structural studies of various forms of the LTTR DntR. Crystal structures of apo-DntR and of a partially autoinducing mutant H169T-DntR suggest that active and inactive DntR maintain a compact homotetrameric configuration. However, Small Angle X-ray Scattering (SAXS) studies on solutions of apo-, H169T- and inducer-bound holo-DntR indicate a different behaviour, suggesting that while apo-DntR maintains a compact configuration in solution both H169T- and holo-DntR adopt an expanded conformation. Models of the SAXS-obtained solution conformations of apo- and holo-DntR homotetramers in complex with promoter-operator region DNA are consistent with previous observations of a shifting of LTTR DNA binding sites upon activation and a consequent relaxation in the bend of the promoter-operator region DNA. Our results thus provide clear evidence at the molecular level which strongly supports the 'sliding dimer' hypothesis concerning LTTR activation mechanisms.

  7. Astrophysical S factor of the 12C(α ,γ )6O reaction calculated with reduced R -matrix theory

    Science.gov (United States)

    An, Zhen-Dong; Chen, Zhen-Peng; Ma, Yu-Gang; Yu, Jian-Kai; Sun, Ye-Ying; Fan, Gong-Tao; Li, Yong-Jiang; Xu, Hang-Hua; Huang, Bo-Song; Wang, Kan

    2015-10-01

    Determination of the accurate astrophysical S factor of 12C(α ,γ )16O reaction has been regarded as the holy grail of nuclear astrophysics for decades. In current stellar models, a knowledge of that value to better than 10% is desirable. Due to the practical issues, tremendous experimental and theoretical efforts over nearly 50 years are not able to reach this goal, and the published values contradicted with each other strongly and their uncertainties are two times larger than the required precision. To this end we have developed a reduced R -matrix theory based on the classical R -matrix theory of Lane and Thomas, which treats primary transitions to the ground state and four bound states as the independent reaction channels in the channel spin representation. With the coordination of covariance statistics and error-propagation theory, a global fitting for almost all available experimental data of 16O system has been multi-iteratively analyzed by our powerful code. A reliable, accurate, and self-consistent astrophysical S factor of 12C(α ,γ )16O was obtained with a recommended value Stot(0.3 MeV ) =162.7 ±7.3 keV b (4.5%) which could meet the required precision.

  8. Colitogenic role of tumour necrosis factor (TNF) receptors in trinitrobenzene sulphonic acid colitis: TNF-R1 ablation does not affect systemic inflammatory response.

    Science.gov (United States)

    Yang, Y; Wang, H; Dou, Y; Wang, Y; Han, G; Wang, Renxi; Wang, L; Guo, R; Xiao, H; Li, X; Shen, B; Shi, Y; Chen, G; Li, Y

    2011-09-01

    Tumour necrosis factor (TNF)-α plays a critical role in the pathogenesis of T helper type 1-mediated colitis such as Crohn's disease. However, the roles of its two receptors in mediating pathology remain largely unknown. In this study, trinitrobenzene sulphonic acid (TNBS) was used to induce colitis in TNF-receptor single or double knock-out (DKO) BALB/c mice and in wild-type counterparts. TNF-R1(-/-) mice had significantly less weight loss, reduced mortality, colon shortening and oedema, colon histological damage and lower levels of colon myeloperoxidase compared with wild-type (WT) BALB/c mice. A similar manifestation was also observed in TNF-R2(-/-) and TNF-R1(-/-) TNF-R2(-/-) (TNF-R DKO) mice. Strikingly, systemic inflammatory response (including splenomegaly and monocyte expansion) was found in WT and TNF-R1(-/-) mice after TNBS, instead of TNF-R2(-/-) and TNF-R DKO mice. Attenuated pathology of colitis in TNF-R1(-/-) or TNF-R2(-/-) mice correlated with lower amounts of interleukin (IL)-6, IL-1β, monocyte chemotactic protein (MCP)-1, IL-12p70 and interferon (IFN)-γ production in the colons. Importantly, ablation of TNF-R1 or TNF-R2 reduced the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling (TUNEL)-positive apoptotic epithelial cells in the affected colons compared with WT TNBS-instilled controls, which might be due to the heightened ratio of Bcl-2/Bax and reduced activity of nuclear factor (NF)-κB. These findings suggest that either TNF-R1 or TNF-R2 plays a pathogenic role in the pathology of colitis and TNF signalling via TNF-R1 or TNF-R2 alone is not sufficient for inducing mucosal damage.

  9. The time factor in two Slovak editions of the novel El río oscuro by Alfredo Varela

    Directory of Open Access Journals (Sweden)

    Eva Palkovičová

    2012-12-01

    Full Text Available The aim of this study is to compare of two Slovak editions of the novel El río oscuro by the Argentinian writer Alfredo Varela. This novel was first published in Slovak in 1951 as a translation by Vladimír Oleríny and in 1968 was republished in a new edition with significant changes to the translation. Since we are dealing with two different editions of the same translation published in the span of 17 years, it is interesting to examine the influence of the time factor on the translation itself, the edition, revision and re-edition of this literary work. Following a comparative analysis of the two texts, we came to the conclusion that the edition from 1951 bears all hallmarks of a novice translator’s idiolect, however it also reflects the short tradition of translating from Spanish into Slovak. In the 1968 edition there is a marked change in the translator’s perspective, concerning, above all, the relation of ‘the foreign’ to ‘the domestic’. There also is a clearer and pronounced translation strategy, reflecting the abilities of an experienced translator, the development of the target language and the development of the Slovak theory of translation. It seems to us that the influence of the time factor is visible in both editions examined and, it would with no doubt manifest in a possible third edition of Oleríny’s translation, or, as the case may be, in another translation of Valera’s El río oscuro.

  10. Novel R2R3-MYB transcription factors from Prunus Americana regulates differential patterns of anthocyanin accumulation in tobacco and citrus

    Science.gov (United States)

    The levels of anthocyanins in plants vary widely among cultivars, developmental stages and environmental stimuli. Previous studies have reported that the expression of various MYBs regulate anthocyanin pigmentation during growth and development. Here we examine the activity of three novel R2R3-MYB ...

  11. Factor analysis of the WISC-R (Spanish version) at 11 age levels between 6 1/2 and 16 1/2 years.

    Science.gov (United States)

    Gass, C S; Demsky, Y I; Martin, P C

    1998-01-01

    The Spanish version of the Wechsler Intelligence Scale for Children-Revised (WISC-R, Wechsler, 1974)-the Escala de Inteligencia para Niños-Revision (EIWN-R, Wechsler, 1982)-has a potentially important role in the assessment of Hispanic children. However, little is known regarding its psychometric characteristics. This study used the normative data from the EIWN-R standardization sample (N = 532 Cuban Americans) to examine its factorial composition and general comparability with the WISC-R. Within each of the 11 age groups (ages 6 1/2 to 16 1/2), the correlation matrix of raw scores was subjected to a principal components analysis and varimax rotation. The results supported a 2-factor solution across age groups roughly corresponding with Wechsler's verbal and performance dimensions. The existence of a meaningful third factor, which has empirical support in the WISC-R literature, failed to emerge for the EIWN-R.

  12. Attributes for NHDPlus Catchments (Version 1.1) for the Conterminous United States: Mean Annual R-factor, 1971-2000

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This data set represents the average annual R-factor, rainfall-runoff erosivity measure, compiled for every catchment of NHDPlus for the conterminous United States....

  13. Attributes for MRB_E2RF1 Catchments by Major River Basins in the Conterminous United States: Mean Annual R-factor, 1971-2000

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This tabular data set represents the average annual R-factor, rainfall-runoff erosivity measure, compiled for every MRB_E2RF1 catchment of selected Major River...

  14. eIF2α kinases regulate development through the BzpR transcription factor in Dictyostelium discoideum.

    Directory of Open Access Journals (Sweden)

    Charles K Singleton

    Full Text Available BACKGROUND: A major mechanism of translational regulation in response to a variety of stresses is mediated by phosphorylation of eIF2α to reduce delivery of initiator tRNAs to scanning ribosomes. For some mRNAs, often encoding a bZIP transcription factor, eIF2α phosphorylation leads to enhanced translation due to delayed reinitiation at upstream open reading frames. Dictyostelium cells possess at least three eIF2α kinases that regulate various portions of the starvation-induced developmental program. Cells possessing an eIF2α that cannot be phosphorylated (BS167 show abnormalities in growth and development. We sought to identify a bZIP protein in Dictyostelium whose production is controlled by the eIF2α regulatory system. PRINCIPAL FINDINGS: Cells disrupted in the bzpR gene had similar developmental defects as BS167 cells, including small entities, stalk defects, and reduced spore viability. β-galactosidase production was used to examine translation from mRNA containing the bzpR 5' UTR. While protein production was readily apparent and regulated temporally and spatially in wild type cells, essentially no β-galactosidase was produced in developing BS167 cells even though the lacZ mRNA levels were the same as those in wild type cells. Also, no protein production was observed in strains lacking IfkA or IfkB eIF2α kinases. GFP fusions, with appropriate internal controls, were used to directly demonstrate that the bzpR 5' UTR, possessing 7 uORFs, suppressed translation by 12 fold. Suppression occurred even when all but one uORF was deleted, and translational suppression was removed when the ATG of the single uORF was mutated. CONCLUSIONS: The findings indicate that BzpR regulates aspects of the development program in Dictyostelium, serving as a downstream effector of eIF2α phosphorylation. Its production is temporally and spatially regulated by eIF2α phosphorylation by IfkA and IfkB and through the use of uORFs within the bzpR 5' UTR.

  15. Myeloprotective Action of Combined Application of Ukrainian Recombinant Granulocyte Colony Stimulating Factor (r-GCSF and Enterosorbent С2 in Rats with Malignant Guerin Carcinoma

    Directory of Open Access Journals (Sweden)

    Todor, I.M.

    2015-03-01

    Full Text Available The aim of the study is to analyze myeloprotective effect of novel enterosorbents alone and in combination with two recombinant granulocyte colony stimulating factors: Neupogen (Switzerland and r- GCSF (Ukraine. It is proven that Ukrainian version of recombinant granulocyte colony stimulating factor r-GCSF does not concede officinal drug Neupogen (Switzerland by its experimental therapeutic action and combined use with enterosorbent C2 significantly increases myeloprotective effect of both GCSF versions.

  16. Study of human factors and its basic aspects, focusing the operators of IEA-R1 research reactor

    Energy Technology Data Exchange (ETDEWEB)

    Martins, Maria da Penha Sanches; Andrade, Delvonei Alves de [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)]. E-mails: penhamartins@yahoo.com.br; delvonei@ipen.br

    2007-07-01

    The objective of this work is the study of human factors and situational variables, which, when modified, can interfere in the work actions of the operators of nuclear installations. This work is focused on the operators of the IEA-R1 research reactor, which is located in the Instituto de Pesquisas Energeticas e Nucleares - IPEN - CNEN/SP. The accidents in Nuclear Plants have shown that the most serious have occurred due to human failure. This work also considers the item 5.5.3 of CNEN-NN-3.01 standard - 'Actions must be taken to reduce, as much as possible, the human failures that may lead to accidents or even other events which may originate inadvertent or unintentional expositions in any individual'. The model named - Behavioral Analysis - is adopted. Relevant factors and aspects of the operators' routine are also considered. It is worth to remind that the performance depends on a series of variables, not only on the individual, but also the situational ones, which include physical, work, environment, organizational and social variables. Subjective factors are also considered, such as: attitude, ability, motivation etc., aiming at a global perspective of the situation, which counts on a set of principles for the behavior analysis and comprehension. After defining the applicability scenario, mechanisms and corrective actions to contribute with the reduction of failures will be proposed. (author)

  17. Study of human factors and its basic aspects, focusing the operators of IEA-R1 research reactor

    Energy Technology Data Exchange (ETDEWEB)

    Martins, Maria da Penha Sanches; Andrade, Delvonei Alves de [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)]. E-mails: penhamartins@yahoo.com.br; delvonei@ipen.br

    2008-03-15

    Human factors and situational variables, which ca, when modified, interfere in the actions of operators of nuclear installations is studied. This work is focused in the operators of the IEA-R1 research reactor, which is located in the Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Brazil. The accidents in Nuclear Plants have shown that the most serious have occurred due to human failure. This work also considers the item 5.5.3 of CNEN-NN-3.01 standard - 'Actions must be taken to reduce, as much as possible, the human failures that can lead to accidents or even other events which can originate inadvertent or unintentional expositions in any individual'. The model named 'Behavioral Analysis' is adopted. Relevant factors and aspects of the operators' routine are also considered. It is worth to remind that the performance depends on a series of variables, not only on the individual, but also situational, including in these categories; physical variables, work environment, organizational and the social ones. The subjective factors are also considered, such as: attitude, ability, motivation etc., aiming at a global perspective of the situation, which counts on a set of principles for the behaviour analysis and comprehension. After defining the applicability scenario, mechanisms and corrective actions to contribute with the reduction of failures will be proposed. (author)

  18. miR-19, a component of the oncogenic miR-17∼92 cluster, targets the DNA-end resection factor CtIP

    DEFF Research Database (Denmark)

    Hühn, D; Kousholt, A N; Sørensen, Claus Storgaard

    2014-01-01

    to two highly conserved sequences located in the 3'-untranslated region of CtIP mRNA. We further demonstrate that CtIP expression is repressed by miR-19 during continuous genotoxic stress in a p53-dependent manner. Finally, we report that miR-19 impairs CtIP-mediated DNA-end resection, which results......R-19 still remain largely elusive. CtIP/RBBP8 promotes DNA-end resection, a critical step in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR), and is considered to function as a tumor suppressor. In this study, we show that miR-19 downregulates CtIP expression by binding...... in reduced HR levels and DNA damage hypersensitivity. By downregulating CtIP, miR-19 overexpression suppresses the faithful repair of DSBs that is crucial for genome maintenance. Our findings thus provide new mechanistic insight into the oncogenic role of the miR-17∼92 cluster.Oncogene advance online...

  19. Astrophysical S factor of {$^{12}$C($\\alpha,\\gamma$)$^{16}$O} Calculated with the Reduced R-matrix Theory

    CERN Document Server

    An, Zhen-Dong; Ma, Yu-Gang; Yu, Jian-Kai; Sun, Ye-Ying; Fan, Gong-Tao; Li, Yong-Jiang; Xu, Hang-Hua; Huang, Bo-Song; Wang, Kan

    2015-01-01

    Determination of the accurate astrophysical S factor of {$^{12}$C($\\alpha,\\gamma$)$^{16}$O} reaction has been regarded as a holy grail of nuclear astrophysics for decades. In current stellar models, a knowledge of that value to better than 10\\% is desirable. Due to the practical issues, tremendous experimental and theoretical efforts over nearly 50 years are not able to reach this goal, and the published values contradicted with each other strongly and their uncertainties are 2 times larger than the required precision. To this end we have developed a Reduced R-matrix Theory, based on the classical R-matrix theory of Lane and Thomas, which treats primary transitions to ground state and four bound states as the independent reaction channels in the channel spin representation. With the coordination of covariance statistics and error propagation theory, a global fitting for almost all available experimental data of $^{16}$O system has been multi-iteratively analyzed by our powerful code. A reliable, accurate and ...

  20. R1507, an anti-insulin-like growth factor-1 receptor (IGF-1R antibody, and EWS/FLI-1 siRNA in Ewing's sarcoma: convergence at the IGF/IGFR/Akt axis.

    Directory of Open Access Journals (Sweden)

    Helen J Huang

    Full Text Available A subset of patients with Ewing's sarcoma responds to anti-insulin-like growth factor-1 receptor (IGF-1R antibodies. Mechanisms of sensitivity and resistance are unknown. We investigated whether an anti-IGF-1R antibody acts via a pathway that could also be suppressed by small interfering (si RNA against the EWS/FLI-1 fusion protein, the hallmark of Ewing's sarcoma. The growth of two Ewing's sarcoma cell lines (TC-32 and TC-71 was inhibited by the fully human anti-IGF-1R antibody, R1507 (clonogenic and MTT assays. TC-32 and TC-71 cells express high levels of IGF-2, while RD-ES and A4573 Ewing's cell lines, which were less responsive to R1507 in our assays, express low or undetectable IGF-2, respectively. TC-71 cells also expressed high levels of IGF-1R, and R1507 decreased steady-state levels of this receptor by internalization/degradation, an effect which was associated with a decrease in p-IGF-1R, p-IRS-1, and p-Akt. EWS/FLI-1 siRNA also decreased p-Akt, due to its ability to increase IGF-BP3 levels and subsequently decrease IGF-1 and IGF-2 levels, thus inhibiting signaling through p-IGF-1R. This inhibition correlated with growth suppression and apoptosis. The attenuation of Akt activation was confirmed in TC-71 and HEK-293 (human embryonic kidney cells by transfecting them with IGF-1R siRNA. We conclude that antibodies and siRNA to IGF-1R, as well as siRNA to EWS/FLI-1, act via intersecting IGF/IGF-1R signals that suppress a common point in this pathway, namely the phosphorylation of Akt.

  1. The French Version of the Screen for Child Anxiety Related Emotional Disorders-Revised (Scared-R: Factor Structure, Convergent and Divergent Validity in a Sample of Teenagers

    Directory of Open Access Journals (Sweden)

    Martine Bouvard

    2013-06-01

    Full Text Available The principal objective of this study is to provide data on the French version of the SCARED-R. This article investigates the factor structure of the French version of the Screen for Child Anxiety Related Emotional Disorders-Revised (SCARED-R and its convergent and divergent validity. 704 normal adolescents aged 10 to 19 years completed the questionnaires in their classrooms. A sub-sample of 595 adolescents also completed an anxiety questionnaire (the French version of the Fear Survey Schedule for Children-Revised, FSSC-R and a depression questionnaire (the French version of the Center for Epidemiological Studies Depression Scale, CES-D. Confirmatory factor analysis of the SCARED-R suggested reasonable fit for the 9-factor model. The comparison of the convergent and divergent validity revealed that the SCARED-R total score and five SCARED-R subscales (SAD, Social Phobia and the three Specific Phobias correlated more strongly with anxiety than depression. The other SCARED-R subscales (GAD, Panic Disorder, OCD and PTSD are positively related to levels of anxiety and depression. Altogether, the French version of the SCARED-R showed reasonable psychometric properties.

  2. Soybean miR172c Targets the Repressive AP2 Transcription Factor NNC1 to Activate ENOD40 Expression and Regulate Nodule Initiation[C][W

    Science.gov (United States)

    Wang, Youning; Wang, Lixiang; Zou, Yanmin; Chen, Liang; Cai, Zhaoming; Zhang, Senlei; Zhao, Fang; Tian, Yinping; Jiang, Qiong; Ferguson, Brett J.; Gresshoff, Peter M.; Li, Xia

    2014-01-01

    MicroRNAs are noncoding RNAs that act as master regulators to modulate various biological processes by posttranscriptionally repressing their target genes. Repression of their target mRNA(s) can modulate signaling cascades and subsequent cellular events. Recently, a role for miR172 in soybean (Glycine max) nodulation has been described; however, the molecular mechanism through which miR172 acts to regulate nodulation has yet to be explored. Here, we demonstrate that soybean miR172c modulates both rhizobium infection and nodule organogenesis. miR172c was induced in soybean roots inoculated with either compatible Bradyrhizobium japonicum or lipooligosaccharide Nod factor and was highly upregulated during nodule development. Reduced activity and overexpression of miR172c caused dramatic changes in nodule initiation and nodule number. We show that soybean miR172c regulates nodule formation by repressing its target gene, Nodule Number Control1, which encodes a protein that directly targets the promoter of the early nodulin gene, ENOD40. Interestingly, transcriptional levels of miR172c were regulated by both Nod Factor Receptor1α/5α-mediated activation and by autoregulation of nodulation-mediated inhibition. Thus, we established a direct link between miR172c and the Nod factor signaling pathway in addition to adding a new layer to the precise nodulation regulation mechanism of soybean. PMID:25549672

  3. Assembly factors Rpf2 and Rrs1 recruit 5S rRNA and ribosomal proteins rpL5 and rpL11 into nascent ribosomes.

    Science.gov (United States)

    Zhang, Jingyu; Harnpicharnchai, Piyanun; Jakovljevic, Jelena; Tang, Lan; Guo, Yurong; Oeffinger, Marlene; Rout, Michael P; Hiley, Shawna L; Hughes, Timothy; Woolford, John L

    2007-10-15

    More than 170 proteins are necessary for assembly of ribosomes in eukaryotes. However, cofactors that function with each of these proteins, substrates on which they act, and the precise functions of assembly factors--e.g., recruiting other molecules into preribosomes or triggering structural rearrangements of pre-rRNPs--remain mostly unknown. Here we investigated the recruitment of two ribosomal proteins and 5S ribosomal RNA (rRNA) into nascent ribosomes. We identified a ribonucleoprotein neighborhood in preribosomes that contains two yeast ribosome assembly factors, Rpf2 and Rrs1, two ribosomal proteins, rpL5 and rpL11, and 5S rRNA. Interactions between each of these four proteins have been confirmed by binding assays in vitro. These molecules assemble into 90S preribosomal particles containing 35S rRNA precursor (pre-rRNA). Rpf2 and Rrs1 are required for recruiting rpL5, rpL11, and 5S rRNA into preribosomes. In the absence of association of these molecules with pre-rRNPs, processing of 27SB pre-rRNA is blocked. Consequently, the abortive 66S pre-rRNPs are prematurely released from the nucleolus to the nucleoplasm, and cannot be exported to the cytoplasm.

  4. Reduced Levels of microRNAs miR-124a and miR-150 Are Associated with Increased Proinflammatory Mediator Expression in Krüppel-like Factor 2 (KLF2)-deficient Macrophages*

    Science.gov (United States)

    Manoharan, Palanikumar; Basford, Joshua E.; Pilcher-Roberts, Robyn; Neumann, Jonathan; Hui, David Y.; Lingrel, Jerry B.

    2014-01-01

    Previous studies have shown that the myeloid-specific deficiency of the transcription factor Krüppel-like factor 2 (KLF2) accelerates atherosclerosis in hypercholesterolemic Ldlr−/− mice due to the enhanced adhesion of myeloid cells to activated endothelial cells in the vessel wall. This study revealed elevated basal inflammation with elevated plasma levels of Ccl2, Ccl4, Ccl5, and Ccl11 in the myeloid-specific KLF2 knock-out (myeKlf2−/−) mice. Peritoneal macrophages isolated from myeKlf2−/− mice showed increased mRNA levels of several inflammatory mediators, including Ccl2, Ccl5, Ccl7, Cox-2, Cxcl1, and IL-6. In contrast, the levels of two microRNAs, miR-124a and miR-150, were lower in Klf2−/− macrophages compared with Klf2+/+ macrophages. Additional studies showed a direct inverse relationship between miR-124a levels with Ccl2 expression, with anti-miR-124a increasing Ccl2 mRNA levels in Klf2+/+ macrophages, whereas the restoration of miR-124a levels in Klf2−/− macrophages significantly reduced Ccl2 mRNA expression. Likewise, the inverse relationship was observed between miR-150 levels and Cxcl1 expression in Klf2+/+ and Klf2−/− mice. Moreover, miR150 likely regulates the miR124a expression and thus augments expression of inflammatory mediators in myeKlf2−/− macrophages. This study documented that the transcription factor KLF2 modulates inflammatory chemokine production via regulation of microRNA expression levels in immune cells. PMID:25248747

  5. (g ,f)-Factorizations (m, r)-Orthogonal to an Arbitrary Graph%与任意图(m,r)-正交的(g,f)-因子分解

    Institute of Scientific and Technical Information of China (English)

    桂国祥

    2013-01-01

    设G是一个图,用V(G)和E(G)分别表示它的顶点集和边集,并设g(x)和f(x)分别是定义在V(G)上的非负整数值函数,且对每个x∈ V(G)有g(x)<f(x),则图G的一个支撑子图F称为G的一个(g,f)-因子,如果对每个x∈V(G),有g(x) ≤dF(x)≤f(x).图G的(g,f)-因子分解是指E(G)能划分成边不交的(g,f)-因子,设F={F1,F2,…,Fm}和H分别是图G的因子分解和子图,若对所有l≤i≤m有|E(H)∩E(Fi)| =r,则称F和H(m,r)-正交.文中定理1得到如下结果:若G是一个(mg +m-l,mf-(m-l)r)-图,H是G的一个有mr条边的子图,则G有一个(g,f)-因子分解与H(m,r)-正交.

  6. (g. f)-Factorizations ( m, r) - Orthogonal to an Arbitrary Graph%与任意图(m,r)-正交的(g,f)-因子分解

    Institute of Scientific and Technical Information of China (English)

    桂国祥; 刘展鸿

    2005-01-01

    设G是-个图,用V(G)和E(G)表示它的顶点集和边集,并设g(x)和f(x)是定义在V(G)上的两个整数值函数,且对每个x∈V(G),有(5/2)r-1≤g(x)≤f(x),则图G的一个支撑子图F称为G的一个(g,f)-因子,如果对每个x∈V(G),有g(x)≤dF(x)≤f(x).图G的(g,f)-因子分解是指E(G)能划分成边不交的(g,f)-因子,设F={F1,F2,…,Fm}和H分别是图G的因子分解和子图,若对所有1≤i≤m有|E(H)∩ E(Fi)|=r,则称F和H(m,r)-正交.本文证明:若G是一个(mg+m-1,mf-m+1)-图,H是G中任一有mr条边的子图,则G有一个(g,f)-因子分解与H(m,r)-正交.

  7. miR-483 is Down-Regulated in Polycystic Ovarian Syndrome and Inhibits KGN Cell Proliferation via Targeting Insulin-Like Growth Factor 1 (IGF1)

    Science.gov (United States)

    Xiang, Yungai; Song, Yuxia; Li, Yan; Zhao, Dongmei; Ma, Liying; Tan, Li

    2016-01-01

    Background Polycystic ovarian syndrome (PCOS) is a common metabolic disorder in premenopausal woman, characterized by hyperandrogenism, oligoanovulation, and insulin resistance. microRNAs play pivotal roles in regulating key factors of PCOS. However, relevant research remains limited. This study aimed to reveal the role and potential mechanism of miR-483 in PCOS. Material/Methods PCOS patients (n=20) were recruited for detecting miR-483 expression in lesion and normal ovary cortex. Human granulosa-like tumor cell line KGN was used to alter miR-483 expression by cell transfection. Cell viability and proliferation were analyzed by MTT assay and colony formation assay, and cell cycle was detected by flow cytometry. Interaction between miR-483 and IGF1 was verified by luciferase reporter assay. KGN cells were further treated by insulin to investigate the relationship between miR-483 and insulin. Results miR-483 was significantly down-regulated in lesion ovary cortex from PCOS patients (P<0.001). In KGN cells, overexpression of miR-483 inhibited cell viability and proliferation, and induced cell cycle arrest. miR-483 also inhibited CCNB1, CCND1, and CDK2. miR-483 sponge induced the opposite effects. miR-483 directly targeted IGF1 3′UTR, and IGF1 promoted KGN cell proliferation and reversed miR-483-inhibited cell viability. Insulin treatment in KGN cells inhibited miR-483, and promoted IGF1 and cell proliferation. Conclusions These results suggest that miR-483 is a PCOS suppressor inhibiting cell proliferation, possibly via targeting IGF1, and that it is involved in insulin-induced cell proliferation. miR-483 is a potential alternative for diagnosing and treating PCOS. PMID:27662007

  8. The influencing factors of policy choice on R&D capitalization and expensing%R&D资本化与费用化政策选择的影响因素研究

    Institute of Scientific and Technical Information of China (English)

    王燕妮; 张书菊; 王方

    2013-01-01

    以2007-2010年年报披露研发投入数据的沪深A股上市公司1071个观测值为样本,从R&D投入会计处理方法选择的角度分析企业进行R&D资本化与费用化政策选择的影响因素.研究结果表明:新会计准则对R&D投入会计报告的变革有一定的积极意义,R&D资本化与费用化的选择受到了企业特征的影响.研发强度大、盈利水平低、规模较小、负债水平高、股权分散、研发投入不稳定且处于扭亏临界和高技术行业的公司倾向于选择将R&D资本化,而那些规模较大,盈利水平高、负债率低、股权相对集中、研发投入稳定的企业则倾向于将R&D费用化.另外,R&D资本化与费用化的选择与其系统风险、成长性和收益平滑动机没有显著关系.%Using a sample of 1071 observations from China listed companies that disclosed information on R&D over the period of 2007 - 2010, from the perspective of the accounting treatment of R&D expenditures, this paper studied the influencing factors of policy choice on R&D capitalization and expensing. The empirical findings show that accounting choice for R&D expenditures is affected by the characteristics of the companies. Capitalization is preferred by those companies which are greater R&D intensity, less profitable, smaller size, more highly leverage, lower ownership concentration, non - steady - state of R&D investment, high - tech industry and in the condition of losses. While the firms choosing to expense R&D are larger, higher profitable, lower leveraged, more concentrate ownership and in steady - state for R&D. Moreover, weaker evidence shows any relation between systematic risk, growth, smoothing profits and accounting choice for R&D.

  9. Enterovirus-induced miR-141 contributes to shutoff of host protein translation by targeting the translation initiation factor eIF4E.

    Science.gov (United States)

    Ho, Bing-Ching; Yu, Sung-Liang; Chen, Jeremy J W; Chang, Sui-Yuan; Yan, Bo-Shiun; Hong, Qi-Sheng; Singh, Sher; Kao, Chuan-Liang; Chen, Hsuan-Yu; Su, Kang-Yi; Li, Ker-Chau; Cheng, Chiou-Ling; Cheng, Hao-Wei; Lee, Jen-Yi; Lee, Chun-Nan; Yang, Pan-Chyr

    2011-01-20

    Viruses rely on the host translation machinery to complete their life cycles. Picornaviruses use an internal ribosome entry site to initiate cap-independent protein translation and in parallel host cap-dependent translation is shut off. This process is thought to occur primarily via cleavage of host translation initiation factors eIF4GI and eIF4GII by viral proteases. Here we describe another mechanism whereby miR-141 induced upon enterovirus infection targets the cap-dependent translation initiation factor, eIF4E, for shutoff of host protein synthesis. Knockdown of miR-141 reduces viral propagation, and silencing of eIF4E can completely reverse the inhibitory effect of the miR-141 antagomiR on viral propagation. Ectopic expression of miR-141 promotes the switch from cap-dependent to cap-independent translation. Moreover, we identified a transcription factor, EGR1, which is partly responsible for miR-141 induction in response to enterovirus infection. Our results suggest that upregulation of miR-141 upon enterovirus infection can facilitate viral propagation by expediting the translational switch.

  10. miR-223 contributes to the AGE-promoted apoptosis via down-regulating insulin-like growth factor 1 receptor in osteoblasts.

    Science.gov (United States)

    Qin, Yi; Ye, Jichao; Wang, Peng; Gao, Liangbin; Wang, Suwei; Shen, Huiyong

    2016-01-01

    Advanced glycation end products (AGEs) have been confirmed to induce bone quality deterioration in diabetes mellitus (DM), and to associate with abnormal expression of miRNAs in DM patients or in vitro Recently, miRNAs have been recognized to mediate the onset or progression of DM. In the present study, we investigated the regulation on miR-223 level by AGE-BSA treatment in osteoblast-like MC3T3-E1 cells, with real-time quantitative PCR assay. And then we examined the inhibition of insulin-like growth factor 1 receptor (IGF-1R) expression by miR-223, via targeting of the 3' UTR of IGF-1R with real-time quantitative PCR, western blotting and luciferase reporter assay. Then we explored the regulation of miR-223 and IGF-1R levels, via the lentivirus-mediated miR-223 inhibition and IGF-1R overexpression in the AGE-BSA-induced apoptosis in MC3T3-E1 cells. It was demonstrated that AGE-BSA treatment with more than 100 μg/ml significantly up-regulated miR-223 level, whereas down-regulated IGF-1R level in MC3T3-E1 cells. And the up-regulated miR-223 down-regulated IGF-1R expression in both mRNA and protein levels, via targeting the 3' UTR of IGF-1R Moreover, though the AGE-BSA treatment promoted apoptosis in MC3T3-E1 cells, the IGF-1R overexpression or the miR-223 inhibition significantly attenuated the AGE-BSA-promoted apoptosis in MC3T3-E1 cells. In summary, our study recognized the promotion of miR-223 level by AGE-BSA treatment in osteoblast-like MC3T3-E1 cells. The promoted miR-223 targeted IGF-1R and mediated the AGE-BSA-induced apoptosis in MC3T3-E1 cells. It implies that miR-223 might be an effective therapeutic target to antagonize the AGE-induced damage to osteoblasts in DM.

  11. Physiological changes in fruit ripening caused by overexpression of tomato SlAN2, an R2R3-MYB factor.

    Science.gov (United States)

    Meng, Xia; Yang, Dongyue; Li, Xiaodong; Zhao, Shuya; Sui, Na; Meng, Qingwei

    2015-04-01

    The R2R3-MYB protein SlAN2 has long been thought to be a positive regulator of anthocyanin accumulation. To investigate the role of SlAN2, we have previously overexpressed the gene in tomato. In this work, we analysed physiological characters of the transgenic plants during the fruit ripening. We show that fruits of transformants overexpressing SlAN2 displayed an orange colour, fast softening and elevated ethylene production. Overexpression of SlAN2 resulted in reduction of carotenoid levels via alteration of flux through the carotenoid pathway, elevated ethylene synthesis mainly via upregulation of ethylene biosynthesis genes, and early softening of fruits. We also found that the transcript level of SlRIN, an important ripening-related gene, was up-regulated in transgenic fruits. These results suggest that SlAN2 acts as an important regulator of fruit ripening.

  12. Prognostic Factors and Patterns of Relapse in Ewing Sarcoma Patients Treated With Chemotherapy and R0 Resection

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Hubert Y. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Morani, Ajaykumar [Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wang, Wei-Lien [Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hess, Kenneth R. [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Paulino, Arnold C. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Ludwig, Joseph A. [Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lin, Patrick P. [Department of Orthopedic Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Daw, Najat C. [Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mahajan, Anita, E-mail: amahajan@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2015-06-01

    Purpose: To identify prognostic factors and patterns of relapse for patients with Ewing sarcoma who underwent chemotherapy and R0 resection without radiation therapy (RT). Methods and Materials: We reviewed the medical records of patients who underwent surgical resection at our institution between 2000 and 2013 for an initial diagnosis of Ewing sarcoma. The associations of demographic and clinical factors with local control (LC) and patient outcome were determined by Cox regression. Time to events was measured from the time of surgery. Survival curves were estimated by the Kaplan-Meier method and compared by the log-rank test. Results: A total of 66 patients (median age 19 years, range 4-55 years) met the study criteria. The median follow-up was 5.6 years for living patients. In 43 patients (65%) for whom imaging studies were available, the median tumor volume reduction was 73%, and at least partial response by Response Evaluation Criteria in Solid Tumors was achieved in 17 patients (40%). At 5 years, LC was 78%, progression-free survival (PFS) was 59%, and overall survival (OS) was 65%. Poor histologic response (necrosis ≤95%) was an independent predictor of LC (hazard ratio [HR] 6.8, P=.004), PFS (HR 5.2, P=.008), and OS (HR 5.0, P=.008). Metastasis on presentation was also an independent predictor of LC (HR 6.3, P=.011), PFS (HR 6.8, P=.002), and OS (HR 6.7, P=.002). Radiologic partial response was a predictor of PFS (HR 0.26, P=.012), and postchemotherapy tumor volume was associated with OS (HR 1.06, P=.015). All deaths were preceded by distant relapse. Of the 8 initial local-only relapses, 5 (63%) were soon followed by distant relapse. Predictors of poor postrecurrence survival were time to recurrence <1 year (HR 11.5, P=.002) and simultaneous local and distant relapse (HR 16.8, P=.001). Conclusions: Histologic and radiologic response to chemotherapy were independent predictors of outcome. Additional study is needed to determine the role of adjuvant

  13. Tumores del estroma gastrointestinal (GIST: factores pronósticos de supervivencia tras citorreducción R0 Gastrointestinal stromal tumors (GIST: factors predictive of survival after R0-cytoreduction

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    J. M. Sánchez Hidalgo

    2007-12-01

    Full Text Available Objetivo: analizar los posibles factores pronósticos de supervivencia en tumores estromales gastrointestinales c-kit positivo (GIST, tras citorreducción óptima R0. Pacientes y método: estudio de 35 pacientes intervenidos en nuestra Unidad desde enero 2002 a febrero 2007, con tumores del estroma gastrointestinal CD117/c-kit positivo en los que se alcanzó citorreducción quirúrgica sin residuo tumoral macroscópico. Una base de datos prospectiva nos proporcionó las distintas variables analizadas, de carácter demográfico, anatómico, clínico, histopatológico e inmunohistoquímico, entre otras. El análisis de la supervivencia actuarial se realizó según el método de Kaplan-Meier y el análisis multivariante mediante el método de regresión múltiple de Cox. Resultados: la supervivencia global a 5 años fue del 77%, con una supervivencia media de 52 meses. El riesgo de malignidad según la clasificación de Fletcher y el tamaño tumoral mayor de 10 cm, influyeron significativamente de forma negativa sobre la supervivencia de los pacientes, tras el análisis univariante realizado (p 50% y vivos en la actualidad. Conclusiones: el índice proliferativo Ki-67 podría representar un excelente marcador pronóstico de supervivencia en aquellos pacientes con tumores del estroma gastrointestinal c-kit positivo. Su confirmación y el punto de corte adecuado deberían ser objeto de futuros estudios prospectivos, así como su posible utilidad para seleccionar pacientes candidatos al tratamiento con mesilato de imatinib.Objective: to analyze the different factors predictive of survival associated with optimal R0-cytoreduction in c-kit-positive gastrointestinal stromal tumors. Methods: thirty-five patients were operated on in our Oncological Surgery Department from January 2002 to February 2007 because of CD117/c-kit-positive gastrointestinal stromal tumors, and an optimal surgical cytoreduction was obtained without macroscopical residual disease

  14. Examining the cross-cultural sensitivity of the Revised Two-Factor Study Process Questionnaire (R-SPQ-2F and validation of a Dutch version.

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    Ann Stes

    Full Text Available The Revised Two-Factor Study Process Questionnaire (R-SPQ-2F is used to examine students' study approaches in higher education. The questionnaire assumes to measure two factors: a deep and a surface study approach. Analyses into the validity and reliability of the original English R-SPQ-2F yielded positive results. In this study, we examined the degree to which these positive results can also be found for the Dutch version that we developed. By comparing our results with the results of earlier studies in different cultures, we conclude cross-cultural sensitivity is an important point to be borne in mind when using the R-SPQ-2F. Our research supports the validity and reliability of our Dutch version of the R-SPQ-2F.

  15. Cloning, expression, purification and crystallization of a pair of novel virulence factors, SghA and SghR, from Agrobacterium tumefaciens

    Energy Technology Data Exchange (ETDEWEB)

    Ye, Fuzhou [Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Wang, Chao [Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673 (Singapore); National Cancer Centre Singapore, 11 Hospital Drive, Singapore 169610 (Singapore); Fu, Qinqin [Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Zhang, Lian-hui [Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673 (Singapore); Gao, Yong-gui, E-mail: ygao@ntu.edu.sg [Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673 (Singapore)

    2015-08-25

    The crystallization of the novel virulence factors SghA and SghR is reported. Two proteins, SghA and SghR, which were recently identified and characterized as novel bacterial virulence factors regulating the infection of plant hosts by Agrobacterium, were cloned, overexpressed and purified with high yield. Both SghA and SghR form dimers in solution. The purified SghA and SghR were crystallized and the crystals diffracted to 1.9 and 2.1 Å resolution, respectively. Data were collected and processed, and the crystallographic parameters were within acceptable ranges. These results will help in the determination of their structures in order to uncover the molecular mechanism of how these two proteins together control the release of plant defence signals against agrobacteria during pathogen–host interaction.

  16. Molecular cloning, pathologically-correlated expression and functional characterization of the colonystimulating factor 1 receptor (CSF-1R) gene from a teleost, Plecoglossus altivelis.

    Science.gov (United States)

    Chen, Qiang; Lu, Xin-Jiang; Li, Ming-Yun; Chen, Jiong

    2016-03-18

    Colony-stimulating factor 1 receptor (CSF-1R) is an important regulator of monocytes/macrophages (MO/MΦ). Although several CSF-1R genes have been identified in teleosts, the precise role of CSF- 1R in ayu (Plecoglossus altivelis) remains unclear. In this study, we characterized the CSF-1R homologue from P. altivelis, and named it PaCSF-1R. Multiple sequence alignment and phylogenetic tree analysis showed that PaCSF-1R was most closely related to that of Japanese ricefish (Oryzias latipes). Tissue distribution and expression analysis showed that the PaCSF-1R transcript was mainly expressed in the head kidney-derived MO/MΦ, spleen, and head kidney, and its expression was significantly altered in various tissues upon Vibrio anguillarum infection. After PaCSF-1R neutralization for 48 h, the phagocytic activity of MO/MΦ was significantly decreased, suggesting that PaCSF-1R plays a role in regulating the phagocytic function of ayu MO/MΦ.

  17. Folate deficiency facilitates recruitment of upstream binding factor to hot spots of DNA double-strand breaks of rRNA genes and promotes its transcription.

    Science.gov (United States)

    Xie, Qiu; Li, Caihua; Song, Xiaozhen; Wu, Lihua; Jiang, Qian; Qiu, Zhiyong; Cao, Haiyan; Yu, Kaihui; Wan, Chunlei; Li, Jianting; Yang, Feng; Huang, Zebing; Niu, Bo; Jiang, Zhengwen; Zhang, Ting

    2016-12-06

    The biogenesis of ribosomes in vivo is an essential process for cellular functions. Transcription of ribosomal RNA (rRNA) genes is the rate-limiting step in ribosome biogenesis controlled by environmental conditions. Here, we investigated the role of folate antagonist on changes of DNA double-strand breaks (DSBs) landscape in mouse embryonic stem cells. A significant DSB enhancement was detected in the genome of these cells and a large majority of these DSBs were found in rRNA genes. Furthermore, spontaneous DSBs in cells under folate deficiency conditions were located exclusively within the rRNA gene units, representing a H3K4me1 hallmark. Enrichment H3K4me1 at the hot spots of DSB regions enhanced the recruitment of upstream binding factor (UBF) to rRNA genes, resulting in the increment of rRNA genes transcription. Supplement of folate resulted in a restored UBF binding across DNA breakage sites of rRNA genes, and normal rRNA gene transcription. In samples from neural tube defects (NTDs) with low folate level, up-regulation of rRNA gene transcription was observed, along with aberrant UBF level. Our results present a new view by which alterations in folate levels affects DNA breakage through epigenetic control leading to the regulation of rRNA gene transcription during the early stage of development.

  18. Transgenic wheat expressing Thinopyrum intermedium MYB transcription factor TiMYB2R-1 shows enhanced resistance to the take-all disease.

    Science.gov (United States)

    Liu, Xin; Yang, Lihua; Zhou, Xianyao; Zhou, Miaoping; Lu, Yan; Ma, Lingjian; Ma, Hongxiang; Zhang, Zengyan

    2013-05-01

    The disease take-all, caused by the fungus Gaeumannomyces graminis, is one of the most destructive root diseases of wheat worldwide. Breeding resistant cultivars is an effective way to protect wheat from take-all. However, little progress has been made in improving the disease resistance level in commercial wheat cultivars. MYB transcription factors play important roles in plant responses to environmental stresses. In this study, an R2R3-MYB gene in Thinopyrum intermedium, TiMYB2R-1, was cloned and characterized. The gene sequence includes two exons and an intron. The expression of TiMYB2R-1 was significantly induced following G. graminis infection. An in vitro DNA binding assay proved that TiMYB2R-1 protein could bind to the MYB-binding site cis-element ACI. Subcellular localization assays revealed that TiMYB2R-1 was localized in the nucleus. TiMYB2R-1 transgenic wheat plants were generated, characterized molecularly, and evaluated for take-all resistance. PCR and Southern blot analyses confirmed that TiMYB2R-1 was integrated into the genomes of three independent transgenic wheat lines by distinct patterns and the transgene was heritable. Reverse transcription-PCR and western blot analyses revealed that TiMYB2R-1 was highly expressed in the transgenic wheat lines. Based on disease response assessments for three successive generations, the significantly enhanced resistance to take-all was observed in the three TiMYB2R-1-overexpressing transgenic wheat lines. Furthermore, the transcript levels of at least six wheat defence-related genes were significantly elevated in the TiMYB2R-1 transgenic wheat lines. These results suggest that engineering and overexpression of TiMYB2R-1 may be used for improving take-all resistance of wheat and other cereal crops.

  19. Novel small RNA expression libraries uncover hsa-miR-30b and hsa-miR-30c as important factors in anoikis resistance.

    Science.gov (United States)

    Moreno-Mateos, Miguel A; Barragán, Verónica; Torres, Belén; Rodríguez-Mateo, Cristina; Méndez-Vidal, Cristina; Berezikov, Eugene; Mudduluru, Giridhar; Allgayer, Heike; Pintor-Toro, José A

    2013-12-01

    MicroRNAs (miRNAs) have been widely studied in order to elucidate their biological functions. MicroRNA microarrays or miRNA overexpression libraries generated by synthesis and cloning of individual miRNAs have been used to study their different roles. In this work, we have developed a novel methodology to express mature miRNAs and other small RNAs from a double convergent RNA polymerase III promoter. We show that the generated miRNAs function similarly to those processed from primary transcripts or pri-miRNAs. This system allowed us to produce a lentiviral library expressing the whole population of small RNAs present in a metastatic cell line. A functional screening using this library led to the identification of hsa-miR-30b and hsa-miR-30c as negative regulators of cell death induced by loss of attachment (anoikis). Importantly, we demonstrated that the acquisition of anoikis resistance via these miRNAs is achieved through down-regulation of caspase 3 expression. Moreover, overexpression of these miRNAs resulted in a decrease of other types of caspase 3-dependent cell death and enhanced the survival of MCF10A acinar cells in morphogenesis assays, suggesting a putative role as oncomirs. In summary, this novel methodology provides a powerful and effective way for identifying novel small RNAs involved in a particular biological process.

  20. Transcription factors FabR and FadR regulate both aerobic and anaerobic pathways for unsaturated fatty acid biosynthesis in Shewanella oneidensis

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    Qixia eLuo

    2014-12-01

    Full Text Available As genes for type II fatty acid synthesis are essential to the growth of Escherichia coli, its sole (anaerobic pathway has significant potential as a target for novel antibacterial drug, and has been extensively studied. Despite this, we still know surprisingly little about fatty acid synthesis in bacteria because this anaerobic pathway in fact is not widely distributed. In this study, we show a novel model of unsaturated fatty acid (UFA synthesis in Shewanella, emerging human pathogens in addition to well-known metal reducers. We identify both anaerobic and aerobic UFA biosynthesis pathways in the representative species, S. oneidensis. Uniquely, the bacterium also contains two regulators FabR and FadR, whose counterparts in other bacteria control the anaerobic pathway. However, we show that in S. oneidensis these two regulators are involved in regulation of both pathways, in either direct or indirect manner. Overall, our results indicate that the UFA biosynthesis and its regulation are far more complex than previously expected, and S. oneidensis serves as a good research model for further work.

  1. miR-451通过靶向调控MIF抑制胃癌细胞的迁移与侵袭%miR-451 inhibits migration and invasion of gastric cancer cells by targeting migration inhibitory factor

    Institute of Scientific and Technical Information of China (English)

    张雪梅; 孙延亮; 姚志勇; 王喜梅

    2014-01-01

    目的 探讨miR-451是否通过靶向调控巨噬细胞移动抑制因子(MIF)表达抑制胃癌细胞的迁移和侵袭,从而进一步揭示miR-451的抑瘤机制.方法 运用qRT-PCR检测72例胃癌组织及癌旁正常胃黏膜组织中miR-451的表达改变;采用Western blot检测外源高表达miR-451对MIF蛋白表达水平的影响;然后采用划痕实验和Transwell侵袭实验检测外源高表达miR-451对人胃癌MGC-803细胞迁移和侵袭的影响.结果 qRT-PCR检测结果显示,miR-451在72例胃癌组织中的表达水平较癌旁正常胃黏膜组织明显下调,miR-451的表达水平与胃癌患者的临床分期和淋巴结转移呈负相关;Western blot结果显示,过表达miR-451能下调MIF蛋白的表达.划痕实验和Transwell侵袭实验检测发现,过表达miR-451能抑制MGC-803细胞迁移和侵袭能力,差异均具有统计学意义(P<0.05).结论 miR-451通过靶向调控MIF的表达抑制胃癌细胞的迁移和侵袭.%Objective To explore whether miR-451 suppresses cell migration and invasion by targeting macrophage migration inhibitory factors (MIF),thus to reveal molecular mechanism that miR-451 functions as a tumor suppressor in gastric cancer.Methods A quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to detect the expression of miR-451 in gastric cancer and normal stomach mucosa.Western blotting was performed to detect the expressions of MIF protein regulated by miR-451 in MGC 803 cells.The migration and invasion abilities of MGC-803 cell were evaluated with wound-healing and transwell invasion assays.Results miR-451 was down-regulated in gastric cancer tissues.The expressions of miR-451 were negatively correlated with the clinical stage and lymph node metastasis in gastric cancer patients.Western blot showed that a notable reduction of the protein level of MIF by restoring miR-451 in MGC-803 cells.Overexpression of miR-451 inhibited the migration and invasion of MGC-803 cells.Conclusions miR

  2. Aspectos e fatores da produtividade em pesquisa, desenvolvimento e inovação Aspects and factors for productivity in R&D&I

    Directory of Open Access Journals (Sweden)

    Kurt Politzer

    2005-12-01

    Full Text Available Comparison of national budgets for R&D is often made but it should consider the relative productivity and their factors. In Brazil, inefficiency factors as well as their causes have been diagnosed since the late 60's and solutions have been proposed within various governmental organisms, from CNPq to the strategy think tanks. Problems that hinder R&D and innovation in Brazil are reviewed from a historical perspective together with the proposed solutions providing a detailed analysis of the difficulties that have to be overcome to achieve a more effective innovation environment, adequate for the present times, challenges and opportunities.

  3. Corsi's block-tapping task: standardization and location in factor space with the WAIS-R for two normal samples of older adults.

    Science.gov (United States)

    Saggino, Aristide; Balsamo, Michela; Grieco, Anna; Cerbone, Maria Rosaria; Raviele, Nicla Nicolina

    2004-06-01

    Corsi's block-tapping task and WAIS-R were administered to two Italian samples of 200 normal older adults (aged 65-74 years and 75-100 years). Corsi's reliabilities and standardization data are shown. Additionally, Corsi's location in the factor space of cognitive abilities represented by the 11 WAIS-R subtests is presented. Corsi's test seems to be a reliable one for older Italians. It seems also to be a measure of general intelligence in those 65-74 years of age and a measure of the Freedom from Distractibility factor in subjects 75 years and older.

  4. MiR-451 suppresses proliferation, migration and promotes apoptosis of the human osteosarcoma by targeting macrophage migration inhibitory factor.

    Science.gov (United States)

    Liu, Wei; Liu, Sheng-Yao; He, Yong-Bin; Huang, Rui-Liang; Deng, Song-Yun; Ni, Guo-Xin; Yu, Bin

    2017-03-01

    Previous studies have shown that MiR-451 plays an important role in human osteosarcoma carcinogenesis, but the underlying mechanism by which MiR-451 affects the osteosarcoma has not been fully understood. This study intends to uncover the mechanism by which MiR-451 functions as a tumor suppressor. The expression of MiR-451 in osteosarcoma tissues and osteosarcoma cell lines was monitored by real-time PCR. The proliferation ability was examined by MTT and cell cycle assay. The migration and apoptosis of cells were monitored by migration assay and flow cytometry, respectively. Moreover, the angiogenesis of HUVEC cells transfected with MiR-451 mimics was examined by tube formation assay. The effect of MiR-451 on MIF was determined by luciferase assays and Western blot assay. The results showed that MiR-451 expression level was significantly reduced in the osteosarcoma compared with normal bone tissues. Overexpression of MiR-451 significantly attenuated the proliferation and migration, and induced the apoptosis of osteosarcoma cells. Furthermore, the angiogenesis of HUVEC cells transfected with MiR-451 mimics was assayed and the decreased angiogenic ability was detected compared to the controls. Finally, we demonstrated that MiR-451 overexpression inhibited the malignant behavior of osteosarcoma by downregulating MIF. These findings suggest that MiR-451 may act as a tumor suppressor in osteosarcoma. MiR-451 inhibited cell proliferation, migration and angiogenesis and promoted apoptosis of human osteosarcoma cells, at least partially, by inhibiting the expression of MIF. MiR-451/MIF may be a novel therapeutic target in treatment of osteosarcoma. Copyright © 2016. Published by Elsevier Masson SAS.

  5. miR-27b attenuates apoptosis induced by transmissible gastroenteritis virus (TGEV infection via targeting runt-related transcription factor 1 (RUNX1

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    Xiaomin Zhao

    2016-02-01

    Full Text Available Transmissible gastroenteritis virus (TGEV, belonging to the coronaviridae family, is the key cause of the fatal diarrhea of piglets and results in many pathological processes. microRNAs (miRNAs play a key role in the regulation of virus-induced apoptosis. During the process of apoptosis induced by TGEV infection in PK-15 cells, the miR-27b is notably down-regulated. Thus, we speculate that miR-27b is involved in regulating the process of apoptosis in PK-15 cells. In this study we demonstrated that the over-expression of miR-27b led to the inhibition of TGEV-induced apoptosis, reduction of Bax protein level, and decrease of caspase-3 and −9 activities. Conversely, silencing of miR-27b by miR-27b inhibitors enhanced apoptosis via up-regulating Bax expression and promoting the activities of caspase-3 and −9 in TGEV-infected cells. Subsequently, the runt-related transcription factor 1 (RUNX1 is a candidate target of miR-27b predicted by bioinformatics search. We further identified that the miR-27b directly bound to the 3′ UTR of RUNX1 mRNA and suppressed RUNX1 expression, which indicates RUNX1 is the direct target gene of miR-27b. The over-expression of RUNX1 increased apoptosis and knockdown RUNX1blocked apoptosis of viral-infected cells via regulating Bax expression and the activities of caspase-3 and −9. Our data reveal that miR-27b may repress the mitochondrial pathway of apoptosis by targeting RUNX1, indicating that TGEV may induce apoptosis via down-regulating miR-27b and that miR-27b may act as a target for therapeutic intervention.

  6. miR-320a regulates cell proliferation and apoptosis in multiple myeloma by targeting pre-B-cell leukemia transcription factor 3

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Yinghao [Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis Under Ministry of Health, Collaborative Innovation Center of Hematology, Suzhou, 215006 (China); Department of Hematology, Affiliated Hospital of Guizhou Medical University, The Hematopoietic Stem Cell Transplant Center of Guizhou Province, Blood Diseases Diagnosis and Treatment Center of Guizhou Province, Guiyang, 550004, Guizhou Province (China); Wu, Depei, E-mail: wudepei@medmail.com.cn [Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Key Laboratory of Thrombosis and Hemostasis Under Ministry of Health, Collaborative Innovation Center of Hematology, Suzhou, 215006 (China); Wang, Jishi, E-mail: lgylhlyh@aliyun.com [Department of Hematology, Affiliated Hospital of Guizhou Medical University, The Hematopoietic Stem Cell Transplant Center of Guizhou Province, Blood Diseases Diagnosis and Treatment Center of Guizhou Province, Guiyang, 550004, Guizhou Province (China); Li, Yan; Chai, Xiao; Kang, Qian [Department of Hematology, Affiliated Hospital of Guizhou Medical University, The Hematopoietic Stem Cell Transplant Center of Guizhou Province, Blood Diseases Diagnosis and Treatment Center of Guizhou Province, Guiyang, 550004, Guizhou Province (China)

    2016-05-13

    Aberrant expression of microRNAs (miRNAs) is implicated in cancer development and progression. While miR-320a is reported to be deregulated in many malignancy types, its biological role in multiple myeloma (MM) remains unclear. Here, we observed reduced expression of miR-320a in MM samples and cell lines. Ectopic expression of miR-320a dramatically suppressed cell viability and clonogenicity and induced apoptosis in vitro. Mechanistic investigation led to the identification of Pre-B-cellleukemia transcription factor 3 (PBX3) as a novel and direct downstream target of miR-320a. Interestingly, reintroduction of PBX3 abrogated miR-320a-induced MM cell growth inhibition and apoptosis. In a mouse xenograft model, miR-320a overexpression inhibited tumorigenicity and promoted apoptosis. Our findings collectively indicate that miR-320a inhibits cell proliferation and induces apoptosis in MM cells by directly targeting PBX3, supporting its utility as a novel and potential therapeutic agent for miRNA-based MM therapy. -- Highlights: •Expression of miR-320a in MM cell induces apoptosis in vitro. •miR-320a represses PBX3 via targeting specific sequences in the 3′UTR region. •Exogenous expression of PBX3 reverses the effects of miR-320a in inhibiting MM cell growth and promoting apoptosis. •Overexpression of miR-320a inhibits tumor growth and increases apoptosis in vivo.

  7. MiR-153 targets the nuclear factor-1 family and protects against teratogenic effects of ethanol exposure in fetal neural stem cells

    Directory of Open Access Journals (Sweden)

    Pai-Chi Tsai

    2014-07-01

    Full Text Available Ethanol exposure during pregnancy is an established cause of birth defects, including neurodevelopmental defects. Most adult neurons are produced during the second trimester-equivalent period. The fetal neural stem cells (NSCs that generate these neurons are an important but poorly understood target for teratogenesis. A cohort of miRNAs, including miR-153, may serve as mediators of teratogenesis. We previously showed that ethanol decreased, while nicotine increased miR-153 expression in NSCs. To understand the role of miR-153 in the etiology of teratology, we first screened fetal cortical NSCs cultured ex vivo, by microarray and quantitative RT-PCR analyses, to identify cell-signaling mRNAs and gene networks as important miR-153 targets. Moreover, miR-153 over-expression prevented neuronal differentiation without altering neuroepithelial cell survival or proliferation. Analysis of 3′UTRs and in utero over-expression of pre-miR-153 in fetal mouse brain identified Nfia (nuclear factor-1A and its paralog, Nfib, as direct targets of miR-153. In utero ethanol exposure resulted in a predicted expansion of Nfia and Nfib expression in the fetal telencephalon. In turn, miR-153 over-expression prevented, and partly reversed, the effects of ethanol exposure on miR-153 target transcripts. Varenicline, a partial nicotinic acetylcholine receptor agonist that, like nicotine, induces miR-153 expression, also prevented and reversed the effects of ethanol exposure. These data collectively provide evidence for a role for miR-153 in preventing premature NSC differentiation. Moreover, they provide the first evidence in a preclinical model that direct or pharmacological manipulation of miRNAs have the potential to prevent or even reverse effects of a teratogen like ethanol on fetal development.

  8. MiR-153 targets the nuclear factor-1 family and protects against teratogenic effects of ethanol exposure in fetal neural stem cells.

    Science.gov (United States)

    Tsai, Pai-Chi; Bake, Shameena; Balaraman, Sridevi; Rawlings, Jeremy; Holgate, Rhonda R; Dubois, Dustin; Miranda, Rajesh C

    2014-07-25

    Ethanol exposure during pregnancy is an established cause of birth defects, including neurodevelopmental defects. Most adult neurons are produced during the second trimester-equivalent period. The fetal neural stem cells (NSCs) that generate these neurons are an important but poorly understood target for teratogenesis. A cohort of miRNAs, including miR-153, may serve as mediators of teratogenesis. We previously showed that ethanol decreased, while nicotine increased miR-153 expression in NSCs. To understand the role of miR-153 in the etiology of teratology, we first screened fetal cortical NSCs cultured ex vivo, by microarray and quantitative RT-PCR analyses, to identify cell-signaling mRNAs and gene networks as important miR-153 targets. Moreover, miR-153 over-expression prevented neuronal differentiation without altering neuroepithelial cell survival or proliferation. Analysis of 3'UTRs and in utero over-expression of pre-miR-153 in fetal mouse brain identified Nfia (nuclear factor-1A) and its paralog, Nfib, as direct targets of miR-153. In utero ethanol exposure resulted in a predicted expansion of Nfia and Nfib expression in the fetal telencephalon. In turn, miR-153 over-expression prevented, and partly reversed, the effects of ethanol exposure on miR-153 target transcripts. Varenicline, a partial nicotinic acetylcholine receptor agonist that, like nicotine, induces miR-153 expression, also prevented and reversed the effects of ethanol exposure. These data collectively provide evidence for a role for miR-153 in preventing premature NSC differentiation. Moreover, they provide the first evidence in a preclinical model that direct or pharmacological manipulation of miRNAs have the potential to prevent or even reverse effects of a teratogen like ethanol on fetal development.

  9. OsMYB103L, an R2R3-MYB transcription factor, influences leaf rolling and mechanical strength in rice (Oryza sativa L.)

    OpenAIRE

    Yang, Chunhua; Li, Dayong; Liu, Xue; Ji, Chengjun; Hao, Lili; Zhao, Xianfeng; Li, Xiaobing; Chen, Caiyan; Cheng, Zhukuan; Zhu, Lihuang

    2014-01-01

    Background The shape of grass leaves possesses great value in both agronomy and developmental biology research. Leaf rolling is one of the important traits in rice (Oryza sativa L.) breeding. MYB transcription factors are one of the largest gene families and have important roles in plant development, metabolism and stress responses. However, little is known about their functions in rice. Results In this study, we report the functional characterization of a rice gene, OsMYB103L, which encodes ...

  10. Confirmatory factor analytic investigation of variance composition, gender invariance, and validity of the Male Role Norms Inventory-Adolescent-revised (MRNI-A-r).

    Science.gov (United States)

    Levant, Ronald F; McDermott, Ryon C; Hewitt, Amber A; Alto, Kathleen M; Harris, Kyle T

    2016-10-01

    Confirmatory factor analysis of responses to the Male Role Norms Inventory-Adolescent-revised (MRNI-A-r) from 384 middle school students (163 boys, 221 girls) indicated that the best fit to the data was a bifactor model incorporating the hypothesized 3-factor structure while explicitly modeling an additional, general factor. Specifically, each item-level indicator loaded simultaneously on 2 factors: a general traditional masculinity ideology factor and a specific factor corresponding to 1 of the 3 hypothesized masculine norms for adolescents: Emotionally Detached Dominance, Toughness, and Avoidance of Femininity. Invariance testing across gender supported metric invariance for the general factor only. Although item loadings on the general factor were similar across boys and girls, the specific factor loadings varied substantially, with many becoming nonsignificant in the presence of the general factor for girls. A structural regression analysis predicting latent variables of the Meanings of Adolescent Masculinity Scale (MAMS), the Rosenberg Self-esteem Scale, and the Discipline, School Difficulties, and Positive Behavior Scale (DSDPBS) indicated that the general factor was a strong predictor of MAMS for both genders and DSDPBS for girls. Findings indicate that the MRNI-A-r general factor is a valid and reliable indicator of overall internalization of traditional masculinity ideology in adolescents; however, the specific factors may have different meanings for boys as compared with girls and lack validity in the presence of the general factor. These findings are consistent with a developmental perspective of gender ideology that views adolescence as a time when a differentiated cognitive schema of masculine norms is beginning to develop. (PsycINFO Database Record

  11. The relationship of the angiogenesis regulators VEGF-A, VEGF-R1 and VEGF-R2 to p53 status and prognostic factors in epithelial ovarian carcinoma in FIGO-stages I-II.

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    Skirnisdottir, Ingiridur; Seidal, Tomas; Åkerud, Helena

    2016-03-01

    The aim of this study was to evaluate prognostic effect of the angiogenesis regulators VEGF-R1, VEGF-R2 and VEGF-A for recurrent disease and disease-free survival (DFS), and their relation to the apoptosis regulator p53, in 131 patients with FIGO-stages I-II with epithelial ovarian cancer. For the detection of positivity of the markers the techniques of tissue microarrays and immunohistochemistry (IHC) were used. In tumors the frequency of positive staining for VEGF-R1 was 19%, for VEGF-R2 and VEGF-A, it was 77 and 70%, respectively. Positivity for p53 was detected in 25% of tumors. The total number of recurrences in the complete series was 34 out of 131 (26%) and 5-year disease-free survival (DFS) was 68%. Positive staining for VEGF-A (P=0.030), VEGF-R2 (P=0.011) and p53 (P=0.015) was found more frequently in type II tumors than in type I tumors. Patients with VEGF-R1 negative tumors had worse (P=0.021) DFS compared to patients with VEGF-R1 positive tumors. In two multivariate Cox analyzes with DFS as endpoint, FIGO-stage (HR=3.8), VEGF-R2 status (HR=0.4) and p53 status (HR=2.3), all were significant and independent prognostic factors. When the variables VEGF-R2 and p53 were replaced with the new variable VEGF-R2+p53-/other three combinations in one group, it was found that patients from that subgroup had 86% reduced risk of dying in disease (HR=0.24). Findings above, confirmed relationship between VEGF-R2 and VEGF-A and p53, respectively, with regard to recurrent disease and survival. Some findings from the present study are different from results from previous studies on the regulation of angiogenesis. Despite many trials with anti-angiogenic agents in the front line of ovarian cancer have shown to be positive for progression-free survival, no one has demonstrated an impact on overall survival. Therefore, one of the greatest challenges in ovarian cancer research, is to discover predictive and prognostic biomarkers.

  12. A Novel R2R3-MYB Transcription Factor BpMYB106 of Birch (Betula platyphylla) Confers Increased Photosynthesis and Growth Rate through Up-regulating Photosynthetic Gene Expression.

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    Zhou, Chenguang; Li, Chenghao

    2016-01-01

    We isolated a R2R3-MYB transcription factor BpMYB106, which regulates photosynthesis in birch (Betula platyphylla Suk.). BpMYB106 mainly expresses in the leaf and shoot tip of birch, and its protein is localized in the nucleus. We further fused isolated a 1588 bp promoter of BpMYB106 and analyzed it by PLACE, which showed some cis-acting elements related to photosynthesis. BpMYB106 promoter β-glucuronidase (GUS) reporter fusion studies gene, the result, showed the GUS reporter gene in transgenic birch with BpMYB106 promoter showed strong activities in shoot tip, cotyledon margins, and mature leaf trichomes. The overexpression of BpMYB106 in birch resulted in significantly increased trichome density, net photosynthetic rate, and growth rate as compared with the wild-type birch. RNA-Seq profiling revealed the upregulation of several photosynthesis-related genes in the photosynthesis and oxidative phosphorylation pathways in the leaves of transgenic plants. Yeast one-hybrid analysis, coupled with transient assay in tobacco, revealed that BpMYB106 binds a MYB binding site MYB2 in differentially expressed gene promoters. Thus, BpMYB106 may directly activate the expression of a range of photosynthesis related genes through interacting with the MYB2 element in their promoters. Our study demonstrating the overexpression of BpMYB106-a R2R3-MYB transcription factor-upregulates the genes of the photosynthesis and oxidative phosphorylation pathways to improve photosynthesis.

  13. Structural equivalence and the Neo-Pi-R: Implications for the applicability of the five-factor model of personality in an African context

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    Sumaya Laher

    2008-09-01

    Full Text Available The NEO-PI-R is one of the most widely used and researched operationalisations of the Five Factor Model (FFM of personality (McCrae & Allik, 2002, McCrae & Terraccianno, 2005. Considerable evidence exists in terms of its replicability across cultures leading researchers to conclude that the NEO-PI-R and by extension the FFM are universally applicable. This paper, by virtue of reviewing appropriate literature, argues that evidence for the structural equivalence of the NEO-PI-R, while appropriate in Western cultures, is lacking in non-Western, and specifically African cultures. This is discussed with particular reference to the existence of other factors which are not tapped by this model and which would merit further research.

  14. The sRNA NsiR4 is involved in nitrogen assimilation control in cyanobacteria by targeting glutamine synthetase inactivating factor IF7.

    Science.gov (United States)

    Klähn, Stephan; Schaal, Christoph; Georg, Jens; Baumgartner, Desirée; Knippen, Gernot; Hagemann, Martin; Muro-Pastor, Alicia M; Hess, Wolfgang R

    2015-11-10

    Glutamine synthetase (GS), a key enzyme in biological nitrogen assimilation, is regulated in multiple ways in response to varying nitrogen sources and levels. Here we show a small regulatory RNA, NsiR4 (nitrogen stress-induced RNA 4), which plays an important role in the regulation of GS in cyanobacteria. NsiR4 expression in the unicellular Synechocystis sp. PCC 6803 and in the filamentous, nitrogen-fixing Anabaena sp. PCC 7120 is stimulated through nitrogen limitation via NtcA, the global transcriptional regulator of genes involved in nitrogen metabolism. NsiR4 is widely conserved throughout the cyanobacterial phylum, suggesting a conserved function. In silico target prediction, transcriptome profiling on pulse overexpression, and site-directed mutagenesis experiments using a heterologous reporter system showed that NsiR4 interacts with the 5'UTR of gifA mRNA, which encodes glutamine synthetase inactivating factor (IF)7. In Synechocystis, we observed an inverse relationship between the levels of NsiR4 and the accumulation of IF7 in vivo. This NsiR4-dependent modulation of gifA (IF7) mRNA accumulation influenced the glutamine pool and thus [Formula: see text] assimilation via GS. As a second target, we identified ssr1528, a hitherto uncharacterized nitrogen-regulated gene. Competition experiments between WT and an ΔnsiR4 KO mutant showed that the lack of NsiR4 led to decreased acclimation capabilities of Synechocystis toward oscillating nitrogen levels. These results suggest a role for NsiR4 in the regulation of nitrogen metabolism in cyanobacteria, especially for the adaptation to rapid changes in available nitrogen sources and concentrations. NsiR4 is, to our knowledge, the first identified bacterial sRNA regulating the primary assimilation of a macronutrient.

  15. Insight into the effects of adipose tissue inflammation factors on miR-378 expression and the underlying mechanism.

    Science.gov (United States)

    Jiang, Xinye; Xue, Mei; Fu, Ziyi; Ji, Chenbo; Guo, Xirong; Zhu, Lu; Xu, Lulian; Pang, Lingxia; Xu, Meiyu; Qu, Hongming

    2014-01-01

    Obesity and the related metabolic syndrome have emerged as major public health issues in modern society. miRNAs have been shown to play key roles in regulating obesity-related metabolic syndrome, and some miRNAs regulated by adiponectin were identified as novel targets for controlling adipose tissue inflammation. miR-378 is a candidate target that was shown to be involved in adipose differentiation, mitochondrial metabolism and systemic energy homeostasis. However, little is known about the regulatory mechanisms of miR-378 expression. To better understand the physiological role of miR-378 in obesity and metabolic syndrome, it is crucial that we understand the regulation of miR-378 gene expression in human adipocytes. In this study, we investigated the effects of adipokines and inflammatory cytokines on miR-378 expression using Real-time PCR and the potential regulatory mechanisms using luciferase reporter assays and electrophoretic mobility shift assay (EMSA). Results : We found that adipokines and cytokines upregulated miR-378 expression primarily through SREBP and C/EBP binding sites in the miR-378 promoter region. Our findings showed that adipokines induced miR-378 expression and revealed the most likely mechanism of adipokine-induced miR-378 dysregulation in human adipocytes. miRNAs have been shown to function in regulating obesity-related metabolic syndrome, and miR-378 may be a novel target for controlling adipose tissue inflammation. This study offers a theoretical basis for understanding systemic adipose tissue inflammation and may provide new strategies for clinical treatment. © 2014 S. Karger AG, Basel.

  16. TFmiR: a web server for constructing and analyzing disease-specific transcription factor and miRNA co-regulatory networks.

    Science.gov (United States)

    Hamed, Mohamed; Spaniol, Christian; Nazarieh, Maryam; Helms, Volkhard

    2015-07-01

    TFmiR is a freely available web server for deep and integrative analysis of combinatorial regulatory interactions between transcription factors, microRNAs and target genes that are involved in disease pathogenesis. Since the inner workings of cells rely on the correct functioning of an enormously complex system of activating and repressing interactions that can be perturbed in many ways, TFmiR helps to better elucidate cellular mechanisms at the molecular level from a network perspective. The provided topological and functional analyses promote TFmiR as a reliable systems biology tool for researchers across the life science communities. TFmiR web server is accessible through the following URL: http://service.bioinformatik.uni-saarland.de/tfmir.

  17. Changes in the Expression of Transcription Factors Involved in Modulating the Expression of EPO-R in Activated Human CD4-Positive Lymphocytes.

    Science.gov (United States)

    Lisowska, Katarzyna A; Frackowiak, Joanna E; Mikosik, Anna; Witkowski, Jacek M

    2013-01-01

    We have recently described the presence of the erythropoietin receptor (EPO-R) on CD4(+) lymphocytes and demonstrated that its expression increases during their activation, reaching a level reported to be typical for erythroid progenitors. This observation suggests that EPO-R expression is modulated during lymphocyte activation, which may be important for the cells' function. Here we investigated whether the expression of GATA1, GATA3 and Sp1 transcription factors is correlated with the expression of EPO-R in human CD4(+) lymphocytes stimulated with monoclonal anti-CD3 antibody. The expression of GATA1, GATA3 and Sp1 transcription factors in CD4(+) cells was estimated before and after stimulation with anti-CD3 antibody by Western Blot and flow cytometry. The expression of EPO-R was measured using real-time PCR and flow cytometry. There was no change in the expression of GATA1 and GATA3 in CD4(+) lymphocytes after stimulation with anti-CD3 antibody. However, stimulation resulted in the significantly increased expression of the Sp1 factor. CD4(+) lymphocytes stimulated with anti-CD3 antibody exhibited an increase in both the expression level of EPOR gene and the number of EPO-R molecules on the cells' surface, the latter being significantly correlated with the increased expression of Sp1. Sp1 is noted to be the single transcription factor among the ones studied whose level changes as a result of CD4(+) lymphocyte stimulation. It seems that Sp1 may significantly affect the number of EPO-R molecules present on the surface of activated CD4(+) lymphocytes.

  18. miR-503 inhibits platelet-derived growth factor-induced human aortic vascular smooth muscle cell proliferation and migration through targeting the insulin receptor.

    Science.gov (United States)

    Bi, Rui; Ding, Fangbao; He, Yi; Jiang, Lianyong; Jiang, Zhaolei; Mei, Ju; Liu, Hao

    2016-12-01

    Abnormal proliferation and migration of vascular smooth muscle cells (VSMC) is a common feature of disease progression in atherosclerosis. Here, we investigated the potential role of miR-503 in platelet-derived growth factor (PDGF)-induced proliferation and migration of human aortic smooth muscle cells and the underlying mechanisms of action. miR-503 expression was significantly downregulated in a dose- and time-dependent manner following PDGF treatment. Introduction of miR-503 mimics into cultured SMCs significantly attenuated cell proliferation and migration induced by PDGF. Bioinformatics analyses revealed that the insulin receptor (INSR) is a target candidate of miR-503. miR-503 suppressed luciferase activity driven by a vector containing the 3'-untranslated region of INSR in a sequence-specific manner. Downregulation of INSR appeared critical for miR-503-mediated inhibitory effects on PDGF-induced cell proliferation and migration in human aortic SMCs. Based on the collective data, we suggest a novel role of miR-503 as a regulator of VSMC proliferation and migration through modulating INSR.

  19. SIGN-R1 and complement factors are involved in the systemic clearance of radiation-induced apoptotic cells in whole-body irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jin-Yeon; Loh, SoHee; Cho, Eun-hee [Department of Biomedical Science & Technology, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul, 143-701 (Korea, Republic of); Choi, Hyeong-Jwa [Division of Radiation Effect, Korea Institute of Radiological and Medical Sciences, 215-4, 75 Nowon gil Nowon-Gu, Seoul, 139-706 (Korea, Republic of); Na, Tae-Young [College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-741 (Korea, Republic of); Nemeno, Judee Grace E.; Lee, Jeong Ik [Regenerative Medicine Laboratory, Department of Veterinary Medicine, College of Veterinary Medicine, Konkuk University, Seoul, 143-701 (Korea, Republic of); Yoon, Taek Joon [Department of Food and Nutrition, Yuhan College, Bucheon, Gyeonggi-do, 422-749 (Korea, Republic of); Choi, In-Soo [Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul, 143-701 (Korea, Republic of); Lee, Minyoung [Division of Radiation Effect, Korea Institute of Radiological and Medical Sciences, 215-4, 75 Nowon gil Nowon-Gu, Seoul, 139-706 (Korea, Republic of); Lee, Jae-Seon [Department of Biomedical Sciences, College of Medicine, Inha University, Incheon, 400-712 (Korea, Republic of); Kang, Young-Sun, E-mail: kangys1967@naver.com [Department of Biomedical Science & Technology, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul, 143-701 (Korea, Republic of); Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul, 143-701 (Korea, Republic of)

    2015-08-07

    Although SIGN-R1-mediated complement activation pathway has been shown to enhance the systemic clearance of apoptotic cells, the role of SIGN-R1 in the clearance of radiation-induced apoptotic cells has not been characterized and was investigated in this study. Our data indicated that whole-body γ-irradiation of mice increased caspase-3{sup +} apoptotic lymphocyte numbers in secondary lymphoid organs. Following γ-irradiation, SIGN-R1 and complements (C4 and C3) were simultaneously increased only in the mice spleen tissue among the assessed tissues. In particular, C3 was exclusively activated in the spleen. The delayed clearance of apoptotic cells was markedly prevalent in the spleen and liver of SIGN-R1 KO mice, followed by a significant increase of CD11b{sup +} cells. These results indicate that SIGN-R1 and complement factors play an important role in the systemic clearance of radiation-induced apoptotic innate immune cells to maintain tissue homeostasis after γ-irradiation. - Highlights: • Splenic SIGN-R1{sup +} macrophages are activated after γ-irradiation. • C3 and C4 levels increased and C3 was activated in the spleen after γ-irradiation. • SIGN-R1 mediated the systemic clearance of radiation-induced apoptotic cells in spleen and liver.

  20. Endometrial Cancer Insulin-Like Growth Factor 1 Receptor (IGF1R) Expression Increases with Body Mass Index and Is Associated with Pathologic Extent and Prognosis

    Science.gov (United States)

    Joehlin-Price, Amy S.; Stephens, Julie A.; Zhang, Jianying; Backes, Floor J.; Cohn, David E.; Suarez, Adrian A.

    2016-01-01

    Background Obesity is a main risk factor for endometrial carcinoma (EC). Insulin-like growth factor 1 receptor (IGF1R) expression may influence this association. Methods IGF1R IHC was performed on a tissue microarray with 894 EC and scored according to the percentage and intensity of staining to create immunoreactivity scores, which were dichotomized into low and high IGF1R expression groups. Logistic regression modeling assessed associations with body mass index (BMI), age, histology, pathologic extent of disease (pT), and lymph node metastasis (pN). Overall survival (OS) and disease-free survival (DFS) were compared between IGF1R expression groups using Kaplan–Meier curves and log-rank tests. Results The proportion of patients with high IGF1R expression increased as BMI (<30, 30–39, and 40+ kg/m2) increased (P = 0.002). The adjusted odds of having high IGF1R expression was 1.49 [95% confidence interval (CI), 1.05–2.10, P = 0.024] for patients with BMI 30 to 39 kg/m2 compared with <30 kg/m2 and 1.62 (95% CI, 1.13–2.33, P = 0.009) for patients with BMI 40+ kg/m2 compared with <30 kg/m2. High IGF1R expression was associated with pT and pN univariately and with pT after adjusting for BMI, pN, age, and histologic subtype. DFS and OS were better with high IGF1R expression, P = 0.020 and P = 0.002, respectively, but DFS was not significant after adjusting for pT, pN, and histologic subtype of the tumor. Conclusions There is an association between BMI and EC IGF1R expression. Higher IGF1R expression is associated with lower pT and better DFS and OS. Impact These findings suggest a link between IGF1R EC expression and obesity, as well as IGF1R expression and survival. PMID:26682991

  1. Members of miR-169 family are induced by high salinity and transiently inhibit the NF-YA transcription factor

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    Lin Hongxuan

    2009-04-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are endogenously expressed small RNAs with a length of about 21 nt. MiRNAs silence their target genes at the post-transcriptional level. In plants, miRNAs play various developmental and physiological roles by cleavaging mRNAs predominantly. Drought and high salinity are the most severe environmental abiotic stresses and cause crop losses all over the world. Results In this study, we identified miR-169g and miR-169n (o as high salinity-responsive miRNAs in rice. MiR-169n and miR169o were in a miRNA cluster with a distance of 3707 base pairs (bp. The high degree of conservation and close phylogenic distance of pre-miR-169n and pre-miR-169o indicated that they were derived from a very recent tandem duplication evolutionary event. The existence of a cis-acting abscisic acid responsive element (ABRE in the upstream region of miR-169n (o suggested that miR-169n (o may be regulated by ABA. In our previous study, we found that miR-169g was induced by the osmotic stress caused by drought via a dehydration-responsive element (DRE. Thus, our data showed that there were both overlapping and distinct responses of the miR-169 family to drought and salt stresses. We also showed that these miR-169 members selectively cleaved one of the NF-YA genes, Os03g29760, which is a CCAAT-box binding transcription factor and participates in transcriptional regulation of large number genes. Finally, we found one or more ath-miR-169 member that was also induced by high salinity. Conclusion We identified members of the miR-169 family as salt-induced miRNAs and analyzed their evolution, gene organization, expression, transcriptional regulation motif and target gene. Our data also indicated that the salt-induction of some miR-169 members was a general property in plants.

  2. Members of miR-169 family are induced by high salinity and transiently inhibit the NF-YA transcription factor.

    Science.gov (United States)

    Zhao, Botao; Ge, Liangfa; Liang, Ruqiang; Li, Wei; Ruan, Kangcheng; Lin, Hongxuan; Jin, Youxin

    2009-04-08

    MicroRNAs (miRNAs) are endogenously expressed small RNAs with a length of about 21 nt. MiRNAs silence their target genes at the post-transcriptional level. In plants, miRNAs play various developmental and physiological roles by cleavaging mRNAs predominantly. Drought and high salinity are the most severe environmental abiotic stresses and cause crop losses all over the world. In this study, we identified miR-169g and miR-169n (o) as high salinity-responsive miRNAs in rice. MiR-169n and miR169o were in a miRNA cluster with a distance of 3707 base pairs (bp). The high degree of conservation and close phylogenic distance of pre-miR-169n and pre-miR-169o indicated that they were derived from a very recent tandem duplication evolutionary event. The existence of a cis-acting abscisic acid responsive element (ABRE) in the upstream region of miR-169n (o) suggested that miR-169n (o) may be regulated by ABA. In our previous study, we found that miR-169g was induced by the osmotic stress caused by drought via a dehydration-responsive element (DRE). Thus, our data showed that there were both overlapping and distinct responses of the miR-169 family to drought and salt stresses. We also showed that these miR-169 members selectively cleaved one of the NF-YA genes, Os03g29760, which is a CCAAT-box binding transcription factor and participates in transcriptional regulation of large number genes. Finally, we found one or more ath-miR-169 member that was also induced by high salinity. We identified members of the miR-169 family as salt-induced miRNAs and analyzed their evolution, gene organization, expression, transcriptional regulation motif and target gene. Our data also indicated that the salt-induction of some miR-169 members was a general property in plants.

  3. MiR-338-3p inhibits hepatocarcinoma cells and sensitizes these cells to sorafenib by targeting hypoxia-induced factor 1α.

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    Haitao Xu

    Full Text Available Hypoxia is a common feature of solid tumors and an important contributor to anti-tumor drug resistance. Hypoxia inducible factor-1 (HIF-1 is one of the key mediators of the hypoxia signaling pathway, and was recently proven to be required for sorafenib resistance in hepatocarcinoma (HCC. MicroRNAs have emerged as important posttranslational regulators in HCC. It was reported that miR-338-3p levels are associated with clinical aggressiveness of HCC. However, the roles of miR-338-3p in HCC disease and resistance to its therapeutic drugs are unknown. In this study, we found that miR-338-3p was frequently down-regulated in 14 HCC clinical samples and five cell lines. Overexpression of miR-338-3p inhibited HIF-1α 3'-UTR luciferase activity and HIF-1α protein levels in HepG2, SMMC-7721, and Huh7 cells. miR-338-3p significantly reduced cell viability and induced cell apoptosis of HCC cells. Additionally, HIF-1α overexpression rescued and HIF-1α knock-down abrogated the anti-HCC activity of miR-338-3p. Furthermore, miR-338-3p sensitized HCC cells to sorafenib in vitro and in a HCC subcutaneous nude mice tumor model by inhibiting HIF-1α. Collectively, miR-338-3p inhibits HCC tumor growth and sensitizes HCC cells to sorafenib by down-regulating HIF-1α. Our data indicate that miR-338-3p could be a potential candidate for HCC therapeutics.

  4. miR-200c and phospho-AKT as prognostic factors and mediators of osteosarcoma progression and lung metastasis.

    Science.gov (United States)

    Berlanga, Pablo; Muñoz, Lisandra; Piqueras, Marta; Sirerol, J Antoni; Sánchez-Izquierdo, María Dolors; Hervás, David; Hernández, Miguel; Llavador, Margarita; Machado, Isidro; Llombart-Bosch, Antonio; Cañete, Adela; Castel, Victoria; Font de Mora, Jaime

    2016-08-01

    Lung metastasis is the major cause of death in osteosarcoma patients. However, molecular mechanisms underlying this metastasis remain poorly understood. To identify key molecules related with pulmonary metastasis of pediatric osteosarcomas, we analyzed high-throughput miRNA expression in a cohort of 11 primary tumors and 15 lung metastases. Results were further validated with an independent cohort of 10 primary tumors and 6 metastases. In parallel, we performed immunohistochemical analysis of activated signaling pathways in 36 primary osteosarcomas. Only phospho-AKT associated with lower overall survival in primary tumors, supporting its role in osteosarcoma progression. CTNNB1 expression also associated with lower overall survival but was not strong enough to be considered an independent variable. Interestingly, miR-200c was overexpressed in lung metastases, implicating an inhibitory feed-back loop to PI3K-AKT. Moreover, transfection of miR200c-mimic in U2-OS cells reduced phospho-AKT levels but increased cellular migration and proliferation. Notably, miR-200c expression strongly correlated with miR-141 and with the osteogenic inhibitor miR-375, all implicated in epithelial to mesenchymal transition. These findings contrast epithelial tumors where reduced miR-200c expression promotes metastasis. Indeed, we noted that osteosarcoma cells in the lung also expressed the epithelial marker CDH1, revealing a change in their mesenchymal phenotype. We propose that miR-200c upregulation occurs late in osteosarcoma progression to provide cells with an epithelial phenotype that facilitates their integration in the metastatic lung niche. Thus, our findings identify phospho-AKT in the primary tumor and miR-200c later during tumor progression as prognostic molecules and potential therapeutic targets to prevent progression and metastasis of pediatric osteosarcomas. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  5. NATURAL MUTATION IN THE GENE OF RESPONSE REGULATOR BgrR RESULTING IN REPRESSION OF Bac PROTEIN SYNTHESIS, A PATHOGENICITY FACTOR OF STREPTOCOCCUS AGALACTIAE

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    A. S. Rozhdestvenskaya

    2013-01-01

    Full Text Available Abstract. Streptococcus agalactiae can cause variety of diseases of newborns and adults. For successful colonization of different human tissues and organs as well as for suppression of the host immune system S. agalactiae expresses numerous virulence factors. For coordinated expression of the virulence genes S. agalactiae employs regulatory molecules including regulatory proteins of two-component systems. Results of the present study demonstrated that in S. agalactiae strain A49V the natural mutation in the brgR gene encoding for BgrR regulatory protein, which is component of regulatory system BgrRS, resulted in the repression of Bac protein synthesis, a virulence factor of S. agalactiae. A single nucleotide deletion in the bgrR gene has caused a shift of the reading frame and the changes in the primary, secondary and tertiary structures of the BgrR protein. The loss of functional activity of BgrR protein in A49V strain and repression of Bac protein synthesis have increased virulence of the strain in experimental animal streptococcal infection.

  6. BarR, an Lrp-type transcription factor in Sulfolobus acidocaldarius, regulates an aminotransferase gene in a β-alanine responsive manner.

    Science.gov (United States)

    Liu, Han; Orell, Alvaro; Maes, Dominique; van Wolferen, Marleen; Lindås, Ann-Christin; Bernander, Rolf; Albers, Sonja-Verena; Charlier, Daniel; Peeters, Eveline

    2014-05-01

    In archaea, nothing is known about the β-alanine degradation pathway or its regulation. In this work, we identify and characterize BarR, a novel Lrp-like transcription factor and the first one that has a non-proteinogenic amino acid ligand. BarR is conserved in Sulfolobus acidocaldarius and Sulfolobus tokodaii and is located in a divergent operon with a gene predicted to encode β-alanine aminotransferase. Deletion of barR resulted in a reduced exponential growth rate in the presence of β-alanine. Furthermore, qRT-PCR and promoter activity assays demonstrated that BarR activates the expression of the adjacent aminotransferase gene, but only upon β-alanine supplementation. In contrast, auto-activation proved to be β-alanine independent. Heterologously produced BarR is an octamer in solution and forms a single complex by interacting with multiple sites in the 170 bp long intergenic region separating the divergently transcribed genes. In vitro, DNA binding is specifically responsive to β-alanine and site-mutant analyses indicated that β-alanine directly interacts with the ligand-binding pocket. Altogether, this work contributes to the growing body of evidence that in archaea, Lrp-like transcription factors have physiological roles that go beyond the regulation of α-amino acid metabolism.

  7. Detection of myxoma viruses encoding a defective M135R gene from clinical cases of myxomatosis; possible implications for the role of the M135R protein as a virulence factor

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    Larsen Lars E

    2010-01-01

    Full Text Available Abstract Background Myxoma virus is a member of the Poxviridae and causes disease in European rabbits. Laboratory confirmation of the clinical disease, which occurs in the autumn of most years in Denmark, has been achieved previously using antigen ELISA and electron microscopy. Results An unusually large number of clinically suspected cases of myxomatosis were observed in Denmark during 2007. Myxoma virus DNA was detected, using a new real time PCR assay which targets the M029L gene, in over 70% of the clinical samples submitted for laboratory confirmation. Unexpectedly, further analysis revealed that a high proportion of these viral DNA preparations contained a frame-shift mutation within the M135R gene that has previously been identified as a virulence factor. This frame-shift mutation results in expression of a greatly truncated product. The same frame-shift mutation has also been found recently within an avirulent strain of myxoma virus (6918. However, three other frame-shift mutations found in this strain (in the genes M009L, M036L and M148R were not shared with the Danish viruses but a single nucleotide deletion in the M138R/M139R intergenic region was a common feature. Conclusions It appears that expression of the full-length myxoma virus M135R protein is not required for virulence in rabbits. Hence, the frame-shift mutation in the M135R gene in the nonpathogenic 6918 virus strain is not sufficient to explain the attenuation of this myxoma virus but one/some of the other frame-shift mutations alone or in conjunction with one/some of the thirty two amino acid substitutions must also contribute. The real time PCR assay for myxoma virus is a useful diagnostic tool for laboratory confirmation of suspected cases of myxomatosis.

  8. Detection of myxoma viruses encoding a defective M135R gene from clinical cases of myxomatosis; possible implications for the role of the M135R protein as a virulence factor.

    Science.gov (United States)

    Belsham, Graham J; Polacek, Charlotta; Breum, Solvej Ø; Larsen, Lars E; Bøtner, Anette

    2010-01-16

    Myxoma virus is a member of the Poxviridae and causes disease in European rabbits. Laboratory confirmation of the clinical disease, which occurs in the autumn of most years in Denmark, has been achieved previously using antigen ELISA and electron microscopy. An unusually large number of clinically suspected cases of myxomatosis were observed in Denmark during 2007. Myxoma virus DNA was detected, using a new real time PCR assay which targets the M029L gene, in over 70% of the clinical samples submitted for laboratory confirmation. Unexpectedly, further analysis revealed that a high proportion of these viral DNA preparations contained a frame-shift mutation within the M135R gene that has previously been identified as a virulence factor. This frame-shift mutation results in expression of a greatly truncated product. The same frame-shift mutation has also been found recently within an avirulent strain of myxoma virus (6918). However, three other frame-shift mutations found in this strain (in the genes M009L, M036L and M148R) were not shared with the Danish viruses but a single nucleotide deletion in the M138R/M139R intergenic region was a common feature. It appears that expression of the full-length myxoma virus M135R protein is not required for virulence in rabbits. Hence, the frame-shift mutation in the M135R gene in the nonpathogenic 6918 virus strain is not sufficient to explain the attenuation of this myxoma virus but one/some of the other frame-shift mutations alone or in conjunction with one/some of the thirty two amino acid substitutions must also contribute. The real time PCR assay for myxoma virus is a useful diagnostic tool for laboratory confirmation of suspected cases of myxomatosis.

  9. Targeted therapy of osteosarcoma with radiolabeled monoclonal antibody to an insulin-like growth factor-2 receptor (IGF2R).

    Science.gov (United States)

    Geller, David S; Morris, Jonathan; Revskaya, Ekaterina; Kahn, Mani; Zhang, Wendong; Piperdi, Sajida; Park, Amy; Koirala, Pratistha; Guzik, Hillary; Hall, Charles; Hoang, Bang; Yang, Rui; Roth, Michael; Gill, Jonathan; Gorlick, Richard; Dadachova, Ekaterina

    2016-12-01

    Osteosarcoma overall survival has plateaued around 70%, without meaningful improvements in over 30years. Outcomes for patients with overt metastatic disease at presentation or who relapse are dismal. In this study we investigated a novel osteosarcoma therapy utilizing radioimmunotherapy (RIT) targeted to IGF2R, which is widely expressed in OS. Binding efficiency of the Rhenium-188((188)Re)-labeled IGF2R-specific monoclonal antibody (mAb) to IGF2R on OS17 OS cells was assessed with Scatchard plot analysis. Biodistribution studies were performed in heterotopic murine osteosarcoma xenografts. Tumor growth was compared over a 24-day period post-treatment between mice randomized to receive (188)Re-labeled IGF2R-specific murine mAb MEM-238 ((188)Re-MEM-238) or one of three controls: (188)Re-labeled isotype control mAb, unlabeled MEM-238, or no treatment. Results demonstrate that the radioimmunoconjugate had a high binding constant to IGF2R. Both (188)Re-MEM-238 and the isotype control had similar initial distribution in normal tissue. After 48h (188)Re-MEM-238 exhibited a 1.8 fold selective uptake within tumor compared to the isotype control (p=0.057). Over 24days, the tumor growth ratio was suppressed in animals treated with RIT compared to unlabeled and untreated controls (p=0.005) as demonstrated by a 38% reduction of IGF2R expressing osteosarcoma cells in the RIT group (p=0.002). In conclusion, given the lack of new effective therapies in osteosarcoma, additional investigation into this target is warranted. High expression of IGF2R on osteosarcoma tumors, paired with the specificity and in vivo anti-cancer activity of (188)Re-labeled IGF2R-specific mAb suggests that IGF2R may represent a novel therapeutic target in the treatment of osteosarcoma. This targeted approach offers the benefits of being independent of a specific pathway, a resistance mechanism, and/or an inherent biologic tumor trait and therefore is relevant to all OS tumors that express IGF2R. Copyright

  10. The Network Structure of Human Personality According to the NEO-PI-R: Matching Network Community Structure to Factor Structure

    NARCIS (Netherlands)

    Goekoop, R.; Goekoop, J.G.; Scholte, H.S.

    2012-01-01

    Introduction: Human personality is described preferentially in terms of factors (dimensions) found using factor analysis. An alternative and highly related method is network analysis, which may have several advantages over factor analytic methods. Aim: To directly compare the ability of network comm

  11. Chrysin, Apigenin and Acacetin Inhibit Tumor Necrosis Factor-Related Apoptosis—Inducing Ligand Receptor-1 (TRAIL-R1 on Activated RAW264.7 Macrophages

    Directory of Open Access Journals (Sweden)

    Monika Warat

    2014-06-01

    Full Text Available Expression level of Tumor Necrosis Factor—related apoptosis—inducing ligand (TRAIL receptors is one of the most important factors of TRAIL-mediated apoptosis in cancer cells. We here report for the first time data concerning TRAIL-R1 and TRAIL-R2 receptor expression on RAW264.7 macrophages. Three substances belonging to flavones: chrysin, apigenin and acacetin which differ from their substituents at the 4' position in the phenyl ring were used in assays because of the variety of biological activities (e.g., anticancer activity of the polyphenol compounds. The expression of TRAIL-R1 and TRAIL-R2 death receptors on non-stimulated and LPS (lipopolysaccharide-stimulated macrophages was determined using flow cytometry. We demonstrate that RAW264.7 macrophages exhibit TRAIL-R1 surface expression and that the tested compounds: chrysin, apigenin and acacetin can inhibit TRAIL-R1 death receptor expression level on macrophages.

  12. Overexpression of PtrMYB119, a R2R3-MYB transcription factor from Populus trichocarpa, promotes anthocyanin production in hybrid poplar.

    Science.gov (United States)

    Cho, Jin-Seong; Nguyen, Van Phap; Jeon, Hyung-Woo; Kim, Min-Ha; Eom, Seok Hyun; Lim, You Jin; Kim, Won-Chan; Park, Eung-Jun; Choi, Young-Im; Ko, Jae-Heung

    2016-09-01

    Anthocyanins are a group of colorful and bioactive natural pigments with important physiological and ecological functions in plants. We found an MYB transcription factor (PtrMYB119) from Populus trichocarpa that positively regulates anthocyanin production when expressed under the control of the CaMV 35S promoter in transgenic Arabidopsis Amino acid sequence analysis revealed that PtrMYB119 is highly homologous to Arabidopsis PAP1 (PRODUCTION OF ANTHOCYANIN PIGMENT1), a well-known transcriptional activator of anthocyanin biosynthesis. Independently produced transgenic poplars overexpressing PtrMYB119 or PtrMYB120 (a paralogous gene to PtrMYB119) (i.e., 35S::PtrMYB119 and 35S::PtrMYB120, respectively) showed elevated accumulation of anthocyanins in the whole plants, including leaf, stem and even root tissues. Using a reverse-phase high-performance liquid chromatography, we confirmed that the majority of the accumulated anthocyanin in our transgenic poplar is cyanidin-3-O-glucoside. Gene expression analyses revealed that most of the genes involved in the anthocyanin biosynthetic pathway were highly upregulated in 35S::PtrMYB119 poplars compared with the nontransformed control poplar. Among these genes, expression of PtrCHS1 (Chalcone Synthase1) and PtrANS2 (Anthocyanin Synthase2), which catalyze the initial and last steps of anthocyanin biosynthesis, respectively, was upregulated by up to 350-fold. Subsequent transient activation assays confirmed that PtrMYB119 activated the transcription of both PtrCHS1 and PtrANS2 Interestingly, expression of MYB182, a repressor of both anthocyanin and proanthocyanidin (PA) biosynthesis, was largely suppressed in 35S::PtrMYB119 poplars, while expression of MYB134, an activator of PA biosynthesis, was not changed significantly. More interestingly, high-level accumulation of anthocyanins in 35S::PtrMYB119 poplars did not have an adverse effect on plant growth. Taken together, our results demonstrate that PtrMYB119 and PtrMYB120

  13. R353Q polymorphism in the factor VII gene and cardiovascular risk in Heterozygous Familial Hypercholesterolemia: a case-control study

    Directory of Open Access Journals (Sweden)

    Pérez-Jiménez Francisco

    2011-04-01

    Full Text Available Abstract Background Heterozygous Familial Hypercholesterolemia (FH is a genetic disorder characterized by a high risk of cardiovascular disease. Certain polymorphisms of the factor VII gene have been associated with the development of coronary artery disease and there is a known association between factor VII levels and polymorphic variants in this gene. To date, no study has evaluated the association between factor VII and coronary artery disease in patients with FH. Results This case-control study comprised 720 patients (546 with FH and 174 controls. We determined the prevalence and allele frequencies of the R353Q polymorphism of factor VII, the plasma levels of factor VII antigen (FVII Ag and whether they could be predictive factors for cardiovascular risk. 75% (410 of the patients with FH were RR, 23% (127 RQ and 1.6% (9 QQ; in the control group 75.3% (131 were RR, 21.3% (37 RQ and 3.4% (6 QQ (p = 0.32. No statistically significant associations were observed in the distribution of genotypes and allele frequencies between case (FH and control groups. Nor did we find differences when we evaluated the relationship between the R353Q polymorphism and cardiovascular risk (including coronary disease, ischemic stroke and peripheral arterial disease, either in the univariate analysis or after adjustment for sex, age, arterial hypertension, body mass index, xanthomas, diabetes, smoking, HDLc and LDLc and lipid-lowering treatment. The FVII Ag concentrations behaved in a similar fashion, with no differences for the interaction between controls and those with FH (RR vs. RQ/QQ; p = 0.96. In the subgroup of patients with FH no association was found among cardiovascular disease, genotype and FVII Ag levels (RR vs. RQ/QQ; p = 0.97. Conclusions Our study did not find a direct relationship between cardiovascular risk in patients with Heterozygous Familial Hypercholesterolemia, the R353Q polymorphism of factor VII and FVII Ag levels.

  14. Co-regulation of Iron Metabolism and Virulence Associated Functions by Iron and XibR, a Novel Iron Binding Transcription Factor, in the Plant Pathogen Xanthomonas.

    Science.gov (United States)

    Pandey, Sheo Shankar; Patnana, Pradeep Kumar; Lomada, Santosh Kumar; Tomar, Archana; Chatterjee, Subhadeep

    2016-11-01

    Abilities of bacterial pathogens to adapt to the iron limitation present in hosts is critical to their virulence. Bacterial pathogens have evolved diverse strategies to coordinately regulate iron metabolism and virulence associated functions to maintain iron homeostasis in response to changing iron availability in the environment. In many bacteria the ferric uptake regulator (Fur) functions as transcription factor that utilize ferrous form of iron as cofactor to regulate transcription of iron metabolism and many cellular functions. However, mechanisms of fine-tuning and coordinated regulation of virulence associated function beyond iron and Fur-Fe2+ remain undefined. In this study, we show that a novel transcriptional regulator XibR (named Xanthomonas iron binding regulator) of the NtrC family, is required for fine-tuning and co-coordinately regulating the expression of several iron regulated genes and virulence associated functions in phytopathogen Xanthomonas campestris pv. campestris (Xcc). Genome wide expression analysis of iron-starvation stimulon and XibR regulon, GUS assays, genetic and functional studies of xibR mutant revealed that XibR positively regulates functions involved in iron storage and uptake, chemotaxis, motility and negatively regulates siderophore production, in response to iron. Furthermore, chromatin immunoprecipitation followed by quantitative real-time PCR indicated that iron promoted binding of the XibR to the upstream regulatory sequence of operon's involved in chemotaxis and motility. Circular dichroism spectroscopy showed that purified XibR bound ferric form of iron. Electrophoretic mobility shift assay revealed that iron positively affected the binding of XibR to the upstream regulatory sequences of the target virulence genes, an effect that was reversed by ferric iron chelator deferoxamine. Taken together, these data revealed that how XibR coordinately regulates virulence associated and iron metabolism functions in Xanthomonads in

  15. Recent advancements in small molecule inhibitors of insulin-like growth factor-1 receptor (IGF-1R) tyrosine kinase as anticancer agents.

    Science.gov (United States)

    Negi, Arvind; Ramarao, P; Kumar, Raj

    2013-04-01

    Advancements in understanding of the genetics, genomics, biochemistry and the pharmacology of cancer inhuman, have driven the current cancer chemotherapy to intently focus on development of target-based approaches rather than conventional approaches. From among the various targets identified, validated and inhibited at different hallmarks of cancer, protein tyrosine kinases (PTKs) have been exploited the most. Insulin receptors (IRs), insulin like growth factor receptors (IGF-1R) and their hybrid receptors belong to tyrosine kinase receptor (TKR) family, constitute a structural homology among them and generate a growth promoting IGF system on binding with either insulin, IGF-1 or IGF-2. The system induces the mitogenic effects through a torrent of cell signals produced as a result of cross talk with other growth promoting peptides and steroidal hormones, ultimately resulting in hijacking apoptosis and increasing cell proliferation and cell survival in cancer cells. Various strategies such as anti-IGF-1R antibodies, IGF-1 mimetic peptides, antisense strategies, IGF-1R specific peptide aptamers, targeted degradation of IGF-1R and expression of dominant negative IGF-1R mutants have been explored to inhibit the IGF-1R signaling. However, targeting IGF-1R with small molecules has gained considerable attention in last few years due to their ease of synthesis, ease of optimization of absorption,distribution, metabolism, excretion and toxicity (ADMET) parameters, oral route of administration, lesser side effects and cost effectiveness. The present review provides a broad overview and discusses the highlights on discoveries, SAR studies and binding interactions of small molecules with either IGF-1R active or allosteric sites reported till date.

  16. Purification and growth of melanocortin 1 receptor (Mc1r)- defective primary murine melanocytes is dependent on stem cell factor (SFC) from keratinocyte-conditioned media.

    Science.gov (United States)

    Scott, Timothy L; Wakamatsu, Kazumasa; Ito, Shosuke; D'Orazio, John A

    2009-12-01

    The melanocortin 1 receptor (MC1R) is a transmembrane G(s)-coupled surface protein found on melanocytes that binds melanocyte-stimulating hormone and mediates activation of adenylyl cyclase and generation of the second messenger cyclic AMP (cAMP). MC1R regulates growth and differentiation of melanocytes and protects against carcinogenesis. Persons with loss-offunction polymorphisms of MC1R tend to be UV-sensitive (fair-skinned and with a poor tanning response) and are at high risk for melanoma. Mechanistic studies of the role of MC1R in melanocytic UV responses, however, have been hindered in part because Mc1r-defective primary murine melanocytes have been difficult to culture in vitro. Until now, effective growth of murine melanocytes has depended on cAMP stimulation with adenylyl cyclase-activating or phosphodiesterase-inhibiting agents. However, rescuing cAMP in the setting of defective MC1R signaling would be expected to confound experiments directly testing MC1R function on melanocytic UV responses. In this paper, we report a novel method of culturing primary murine melanocytes in the absence of pharmacologic cAMP stimulation by incorporating conditioned supernatants containing stem cell factor derived from primary keratinocytes. Importantly, this method seems to permit similar pigment expression by cultured melanocytes as that found in the skin of their parental murine strains. This novel approach will allow mechanistic investigation into MC1R's role in the protection against UV-mediated carcinogenesis and determination of the role of melanin pigment subtypes on UV-mediated melanocyte responses.

  17. Local factors modulate tissue-specific NEFA utilization: assessment in rats using 3H-(R)-2-bromopalmitate.

    Science.gov (United States)

    Furler, S M; Cooney, G J; Hegarty, B D; Lim-Fraser, M Y; Kraegen, E W; Oakes, N D

    2000-09-01

    Insulin-resistant states are associated with accumulation of muscle lipid, suggesting an imbalance between lipid uptake and oxidation. We have employed a new fatty-acid tracer [9,10-3H]-(R)-2-bromopalmitate (3H-R-BrP) to study individual-tissue nonesterified fatty acid (NEFA) uptake in states with diminished or enhanced lipid oxidation. 3H-R-BrP was administered to conscious male Wistar rats (approximately 300 g) during fasting (5, 18, or 36 h), acute blockade of beta-oxidation (etomoxir, 15 micromol/kg), and insulin infusion (0.25 U x kg(-1) x h(-1)). Estimates of NEFA clearance rates (K(f)*) and absolute rates of uptake (R(f)*) were calculated from tissue accumulation of 3H-R-BrP products. In the basal state, NEFA uptake was dependent on the oxidative capacity of tissues: R(f)* in brown adipose tissue (BAT) > heart (HRT) > diaphragm (DPHM) > red quadriceps (RQ) > white quadriceps (WQ) > white adipose tissue (WAT). Fasting increased (P < 0.001) K(f)* in WAT but did not change NEFA clearance in other tissues. However, plasma NEFA levels were raised (P < 0.01), tending to elevate R(f)* in most tissues (P < 0.05: WAT, BAT, WQ, DPHM). Etomoxir reduced (P < 0.01) K(f)* only in oxidative tissues (BAT, RQ, DPHM, HRT). Insulin lowered plasma NEFA levels (P < 0.001) and significantly decreased R(f)* in most tissues (P < 0.05: WAT, RQ, DPHM, HRT). An increased (P < 0.05) clearance was observed in WAT, BAT, and WQ; a decrease (P < 0.01) in K(f)* was observed in HRT. This study is the first to measure tissue-specific NEFA uptake in conscious rats in the postabsorptive, fasted, and insulin-stimulated states. We have demonstrated that tissue NEFA utilization is not exclusively determined by systemic availability, but that the early steps of NEFA uptake or metabolic sequestration can also be rapidly modulated by local processes such as NEFA oxidation.

  18. miR-124, -128, and -137 Orchestrate Neural Differentiation by Acting on Overlapping Gene Sets Containing a Highly Connected Transcription Factor Network.

    Science.gov (United States)

    Santos, Márcia C T; Tegge, Allison N; Correa, Bruna R; Mahesula, Swetha; Kohnke, Luana Q; Qiao, Mei; Ferreira, Marco A R; Kokovay, Erzsebet; Penalva, Luiz O F

    2016-01-01

    The ventricular-subventricular zone harbors neural stem cells (NSCs) that can differentiate into neurons, astrocytes, and oligodendrocytes. This process requires loss of stem cell properties and gain of characteristics associated with differentiated cells. miRNAs function as important drivers of this transition; miR-124, -128, and -137 are among the most relevant ones and have been shown to share commonalities and act as proneurogenic regulators. We conducted biological and genomic analyses to dissect their target repertoire during neurogenesis and tested the hypothesis that they act cooperatively to promote differentiation. To map their target genes, we transfected NSCs with antagomiRs and analyzed differences in their mRNA profile throughout differentiation with respect to controls. This strategy led to the identification of 910 targets for miR-124, 216 for miR-128, and 652 for miR-137. The target sets show extensive overlap. Inspection by gene ontology and network analysis indicated that transcription factors are a major component of these miRNAs target sets. Moreover, several of these transcription factors form a highly interconnected network. Sp1 was determined to be the main node of this network and was further investigated. Our data suggest that miR-124, -128, and -137 act synergistically to regulate Sp1 expression. Sp1 levels are dramatically reduced as cells differentiate and silencing of its expression reduced neuronal production and affected NSC viability and proliferation. In summary, our results show that miRNAs can act cooperatively and synergistically to regulate complex biological processes like neurogenesis and that transcription factors are heavily targeted to branch out their regulatory effect. © 2015 AlphaMed Press.

  19. Regulation of heparin-binding EGF-like growth factor by miR-212 and acquired cetuximab-resistance in head and neck squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Hiromitsu Hatakeyama

    Full Text Available BACKGROUND: We hypothesized that chronic inhibition of epidermal growth factor receptor (EGFR by cetuximab, a monoclonal anti-EGFR antibody, induces up-regulation of its ligands resulting in resistance and that microRNAs (miRs play an important role in the ligand regulation in head and neck squamous cell carcinoma (HNSCC. METHODOLOGY/PRINCIPAL FINDINGS: Genome-wide changes in gene and miR expression were determined in cetuximab-sensitive cell line, SCC1, and its resistant derivative 1Cc8 using DNA microarrays and RT-PCR. The effects of differentially expressed EGFR ligands and miRs were examined by MTS, colony formation, ELISA, and western blot assays. Heparin-binding EGF-like growth factor (HB-EGF and its regulator, miR-212, were differentially expressed with statistical significance when SCC1 and 1Cc8 were compared for gene and miR expression. Stimulation with HB-EGF induced cetuximab resistance in sensitive cell lines. Inhibition of HB-EGF and the addition of miR-212 mimic induced cetuximab sensitivity in resistant cell lines. MicroRNA-212 and HB-EGF expression were inversely correlated in an additional 33 HNSCC and keratinocyte cell lines. Six tumors and 46 plasma samples from HNSCC patients were examined for HB-EGF levels. HB-EGF plasma levels were lower in newly diagnosed HNSCC patients when compared to patients with recurrent disease. CONCLUSIONS/SIGNIFICANCE: Increased expression of HB-EGF due to down-regulation of miR-212 is a possible mechanism of cetuximab resistance. The combination of EGFR ligand inhibitors or miR modulators with cetuximab may improve the clinical outcome of cetuximab therapy in HNSCC.

  20. Negative Regulation of Anthocynanin Biosynthesis in Arabidopsis by a miR156-Targeted SPL Transcription Factor

    Energy Technology Data Exchange (ETDEWEB)

    Gou, J.Y.; Liu, C.; Felippes, F. F.; Weigel, D.; Wang, J.-W.

    2011-04-01

    Flavonoids are synthesized through an important metabolic pathway that leads to the production of diverse secondary metabolites, including anthocyanins, flavonols, flavones, and proanthocyanidins. Anthocyanins and flavonols are derived from Phe and share common precursors, dihydroflavonols, which are substrates for both flavonol synthase and dihydroflavonol 4-reductase. In the stems of Arabidopsis thaliana, anthocyanins accumulate in an acropetal manner, with the highest level at the junction between rosette and stem. We show here that this accumulation pattern is under the regulation of miR156-targeted SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) genes, which are deeply conserved and known to have important roles in regulating phase change and flowering. Increased miR156 activity promotes accumulation of anthocyanins, whereas reduced miR156 activity results in high levels of flavonols. We further provide evidence that at least one of the miR156 targets, SPL9, negatively regulates anthocyanin accumulation by directly preventing expression of anthocyanin biosynthetic genes through destabilization of a MYB-bHLH-WD40 transcriptional activation complex. Our results reveal a direct link between the transition to flowering and secondary metabolism and provide a potential target for manipulation of anthocyanin and flavonol content in plants.

  1. The PTPN22 R263Q polymorphism is a risk factor for rheumatoid arthritis in Caucasian case-control samples

    NARCIS (Netherlands)

    Rodriguez-Rodriguez, L.; Taib, W.R.; Topless, R.; Steer, S.; Gonzalez-Escribano, M.F.; Balsa, A.; Pascual-Salcedo, D.; Gonzalez-Gay, M.A.; Raya, E.; Fernandez-Gutierrez, B.; Gonzalez-Alvaro, I.; Bottini, N.; Witte, T.J.M. de; Viken, M.K.; Coenen, M.J.H.; Riel, P.L. van; Franke, B.; Heijer, M. den; Radstake, T.R.D.J.; Wordsworth, P.; Lie, B.A.; Merriman, T.R.; Martin, J.

    2011-01-01

    OBJECTIVE: Recently, a functional PTPN22 variant (R263Q; rs33996649) was found to be associated with systemic lupus erythematosus (SLE). This study was undertaken to analyze the influence of this polymorphism on the risk of rheumatoid arthritis (RA). METHODS: RA patients (n = 5,579) were recruited f

  2. Assessing the Five Factors of Personality in Adolescents: The Junior Version of the Spanish NEO-PI-R

    Science.gov (United States)

    Ortet, Generos; Ibanez, Manuel I.; Moya, Jorge; Villa, Helena; Viruela, Ana; Mezquita, Laura

    2012-01-01

    This article presents the development of a junior version of the Spanish (Castilian) NEO Personality Inventory-Revised (JS NEO) suitable for adolescents aged 12 to 18 years. The psychometric properties of the new JS NEO were investigated using two samples of 2,733 and 983 adolescents in Spain. The results showed that the adult NEO-PI-R factor…

  3. Genotype–phenotype relationship of F7 R353Q polymorphism and plasma factor VII coagulant activity in Asian Indian families predisposed to coronary artery disease

    Indian Academy of Sciences (India)

    Jayashree Shanker; Ganapathy Perumal; Arindam Maitra; Veena S. Rao; B. K. Natesha; Shibu John; Sridhar Hebbagodi; Vijay V. Kakkar

    2009-12-01

    Elevated factor VII (FVII) level is a risk factor for coronary artery disease (CAD). We investigated the role of R353Q polymorphism in the F7 gene in 139 Indian families with CAD, comprising of 222 affected subjects, 105 unaffected subjects and 126 affected sibling pairs. Plasma per cent FVIIc activity (FVII.c activity) differed significantly across R353Q genotype ($P \\lt 0.0001$). Frequency of subjects with RR and QQ genotypes were higher in 4th quartile and 1st quartile of FVII.c activity, respectively ($P \\lt 0.0001$). F7 R353Q SNP was able to explain up to 7% of variation in FVII.c activity by regression analysis and an additive genetic component of variance of 28.04% by heritability analysis. Quantitative trait loci analysis showed suggestive linkage evidence of F7 SNP with per cent FVII.c activity (LOD score $-1.82$; $P = 0.002$). Individuals with RR and RQ genotypes carried an OR of 2.071 (95% c.i. = 1.506–2.850) and 2.472 (95% c.i. = 1.679–3.641), respectively, towards CAD risk. There was significant correlation of FVII.c activity with lipid markers, particularly among those with RR and RQ genotype after covariate adjustment. In conclusion, the F7 R353Q SNP appears to moderately influence plasma FVII.c activity and risk of CAD in Indians.

  4. Genotype-phenotype relationship of F7 R353Q polymorphism and plasma factor VII coagulant activity in Asian Indian families predisposed to coronary artery disease.

    Science.gov (United States)

    Shanker, Jayashree; Perumal, Ganapathy; Maitra, Arindam; Rao, Veena S; Natesha, B K; John, Shibu; Hebbagodi, Sridhar; Kakkar, Vijay V

    2009-12-01

    Elevated factor VII (FVII) level is a risk factor for coronary artery disease (CAD). We investigated the role of R353Q polymorphism in the F7 gene in 139 Indian families with CAD, comprising of 222 affected subjects, 105 unaffected subjects and 126 affected sibling pairs. Plasma per cent FVIIc activity (FVII.c activity) differed ignificantly across R353Q genotype (P F7 R353Q SNP was able to explain up to 7% of variation in FVII.c activity by regression analysis and an additive genetic component of variance of 28.04% by heritability analysis. Quantitative trait loci analysis showed suggestive linkage evidence of F7 SNP with per cent FVII.c activity (LOD score -1.82; P = 0.002). Individuals with RR and RQ genotypes carried an OR of 2.071 (95% c.i. = 1.506-2.850) and 2.472 (95% c.i. = 1.679-3.641), espectively, towards CAD risk. There was significant correlation of FVII.c activity with lipid markers, particularly among those with RR and RQ genotype after covariate adjustment. In conclusion, the F7 R353Q SNP appears to moderately influence plasma FVII.c activity and risk of CAD in Indians.

  5. The Spanish version of the Three Factor Eating Questionnaire-R21 for children and adolescents (TFEQ-R21C): Psychometric analysis and relationships with body composition and fitness variables.

    Science.gov (United States)

    Martín-García, M; Vila-Maldonado, S; Rodríguez-Gómez, I; Faya, F M; Plaza-Carmona, M; Pastor-Vicedo, J C; Ara, I

    2016-10-15

    The main purpose of the present study is to assess the factor structure and reliability of the Spanish version of the 21-item Three Factor Eating Questionnaire (TFEQ-R21C) in children and adolescents and to analyze the relationships between eating behaviors, body composition and cardiovascular fitness. A total of 192 children and adolescents took part in this study (89 boys and 103 girls; aged from 8.8 to 16.8years old and with body mass index (BMI) ranging from 13.2 to 41.1kg/m(2)). None of them had either a history of psychological or eating disorders. Body composition (dual-energy X-ray absorptiometry-DXA), anthropometrics (body mass, height and BMI), cardiovascular fitness (cyclo-ergometer incremental test) and eating behaviors (TFEQ-R21C) were determined in all participants. The confirmatory factor analysis corroborated the same three factors of the original TFEQ-R21: Uncontrolled Eating (UE), Emotional Eating (EE) and Cognitive Restraint (CR). The internal-consistency reliability (Cronbach's alpha coefficient) for the questionnaire was 0.73. Significant differences were found in BMI (F2,189=3.50, p=0.032) and total fat mass (TFM) (F2,189=3.60, p=0.029) between tertiles of the CR scale (children who had the lowest scores, also had lower BMI and fat mass). Cardiovascular fitness (measured by relative VO2 peak) differs depending on the UE and CR scores. The "healthy" group (those who were normal-weight and had also the highest relative VO2 peak) showed a significant lower CR (F3,160=3.07, p=0.030) and higher UE (F3,160=3.86, p=0.011) than the "unhealthy" group (those who were neither normal-weight nor had adequate relative VO2 peak). According to the psychometric analysis of the questionnaire, the TFEQ-R21C is a valid and useful tool to assess eating behaviors in Spanish child population. Further research is necessary to understand the links between eating behaviors and other health-related behaviors such as physical activity time or cardiovascular fitness

  6. Interaction of a partially disordered antisigma factor with its partner, the signaling domain of the TonB-dependent transporter HasR.

    Directory of Open Access Journals (Sweden)

    Idir Malki

    Full Text Available Bacteria use diverse signaling pathways to control gene expression in response to external stimuli. In Gram-negative bacteria, the binding of a nutrient is sensed by an outer membrane transporter. This signal is then transmitted to an antisigma factor and subsequently to the cytoplasm where an ECF sigma factor induces expression of genes related to the acquisition of this nutrient. The molecular interactions involved in this transmembrane signaling are poorly understood and structural data on this family of antisigma factor are rare. Here, we present the first structural study of the periplasmic domain of an antisigma factor and its interaction with the transporter. The study concerns the signaling in the heme acquisition system (Has of Serratia marcescens. Our data support unprecedented partially disordered periplasmic domain of an anti-sigma factor HasS in contact with a membrane-mimicking environment. We solved the 3D structure of the signaling domain of HasR transporter and identified the residues at the HasS-HasR interface. Their conservation in several bacteria suggests wider significance of the proposed model for the understanding of bacterial transmembrane signaling.

  7. Borderline and avoidant personality disorders and the five-factor model of personality: a comparison between DSM-IV diagnoses and NEO-PI-R.

    Science.gov (United States)

    Wilberg, T; Urnes, O; Friis, S; Pedersen, G; Karterud, S

    1999-01-01

    A self-report measure of the Five-Factor Model (FFM) of personality, NEO-PI-R, was administered to a sample of patients with borderline (BPD, N = 29) or avoidant PD (AVPD, N = 34), admitted to a day treatment program, to investigate the NEO-PI-R profiles of the disorders, and the ability of NEO-PI-R to discriminate between the two disorders. The diagnoses were assessed according to the LEAD standard. AVPD was associated with high levels of Neuroticism and Agreeableness, and low levels of Extraversion and Conscientiousness. BPD was associated with high levels of Neuroticism and low levels of Agreeableness, Extraversion, and Conscientiousness. Eighty-eight percent of the AVPD group had high scores on Neuroticism and low scores on Extraversion, whereas 65% of the BPD group were high on Neuroticism and low on Agreeableness. The Extraversion and Agreeableness scales of NEO-PI-R discriminated between patients with BPD and those with AVPD. Patients with BPD scored significantly higher on the Angry Hostility and Impulsiveness subscales of Neuroticism and significantly lower on three Extraversion subscales, three Agreeableness subscales, and one Conscientiousness subscale. At the DSM-IV criterion level, there were more significant relationships between the subscales of NEO-PI-R and the AVPD criteria than with the BPD criteria. The findings suggest that the FFM has good discriminating ability regarding BPD and AVPD. However, there may be a closer conceptual relationship between the FFM and AVPD than between the FFM and BPD.

  8. Two transcription factors, CabA and CabR, are independently involved in multilevel regulation of the biosynthetic gene cluster encoding the novel aminocoumarin, cacibiocin.

    Science.gov (United States)

    Wolański, Marcin; Łebkowski, Tomasz; Kois-Ostrowska, Agnieszka; Zettler, Judith; Apel, Alexander K; Jakimowicz, Dagmara; Zakrzewska-Czerwińska, Jolanta

    2016-04-01

    Aminocoumarins are potent antibiotics belonging to a relatively small group of secondary metabolites produced by actinomycetes. Genome mining of Catenulispora acidiphila has recently led to the discovery of a gene cluster responsible for biosynthesis of novel aminocoumarins, cacibiocins. However, regulation of the expression of this novel gene cluster has not yet been analyzed. In this study, we identify transcriptional regulators of the cacibiocin gene cluster. Using a heterologous expression system, we show that the CabA and CabR proteins encoded by cabA and cabR genes in the cacibiocin gene cluster control the expression of genes involved in the biosynthesis, modification, regulation, and potentially, efflux/resistance of cacibiocins. CabA positively regulates the expression of cabH (the first gene in the cabHIYJKL operon) and cabhal genes encoding key enzymes responsible for the biosynthesis and halogenation of the aminocoumarin moiety, respectively. We provide evidence that CabA is a direct inducer of cacibiocin production, whereas the second transcriptional factor, CabR, is involved in the negative regulation of its own gene and cabT-the latter of which encodes a putative cacibiocin transporter. We also demonstrate that CabR activity is negatively regulated in vitro by aminocoumarin compounds, suggesting the existence of analogous regulation in vivo. Finally, we propose a model of multilevel regulation of gene transcription in the cacibiocin gene cluster by CabA and CabR.

  9. miR-135b Promotes Cancer Progression by Targeting Transforming Growth Factor Beta Receptor II (TGFBR2 in Colorectal Cancer.

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    Jialu Li

    Full Text Available The transforming growth factor beta (TGF-β signaling pathway is a tumor-suppressor pathway that is commonly inactivated in colorectal cancer (CRC. The inactivation of TGFBR2 is the most common genetic event affecting the TGF-β signaling pathway. However, the mechanism by which cancer cells downregulate TGFBR2 is unclear. In this study, we found that the TGFBR2 protein levels were consistently upregulated in CRC tissues, whereas its mRNA levels varied in these tissues, suggesting that a post-transcriptional mechanism is involved in the regulation of TGFBR2. Because microRNAs (miRNAs are powerful post-transcriptional regulators of gene expression, we performed bioinformatic analyses to search for miRNAs that potentially target TGFBR2. We identified the specific targeting site of miR-135b in the 3'-untranslated region (3'-UTR of TGFBR2. We further identified an inverse correlation between the levels of miR-135b and TGFBR2 protein, but not mRNA, in CRC tissue samples. By overexpressing or silencing miR-135b in CRC cells, we experimentally validated that miR-135b directly binds to the 3'-UTR of the TGFBR2 transcript and regulates TGFBR2 expression. Furthermore, the biological consequences of the targeting of TGFBR2 by miR-135b were examined using in vitro cell proliferation and apoptosis assays. We demonstrated that miR-135b exerted a tumor-promoting effect by inducing the proliferation and inhibiting the apoptosis of CRC cells via the negative regulation of TGFBR2 expression. Taken together, our findings provide the first evidence supporting the role of miR-135b as an oncogene in CRC via the inhibition of TGFBR2 translation.

  10. Phosphoglucose isomerase/autocrine motility factor mediates epithelial-mesenchymal transition regulated by miR-200 in breast cancer cells.

    Science.gov (United States)

    Ahmad, Aamir; Aboukameel, Amro; Kong, Dejuan; Wang, Zhiwei; Sethi, Seema; Chen, Wei; Sarkar, Fazlul H; Raz, Avraham

    2011-05-01

    Phosphoglucose isomerase/autocrine motility factor (PGI/AMF) plays an important role in glycolysis and gluconeogenesis and is associated with invasion and metastasis of cancer cells. We have previously shown its role in the induction of epithelial-mesenchymal transition (EMT) in breast cancer cells, which led to increased aggressiveness; however, the molecular mechanism by which PGI/AMF regulates EMT is not known. Here we show, for the first time, that PGI/AMF overexpression led to an increase in the DNA-binding activity of NF-κB, which, in turn, led to increased expression of ZEB1/ZEB2. The microRNA-200s (miR-200s) miR-200a, miR-200b, and miR-200c are known to negatively regulate the expression of ZEB1/ZEB2, and we found that the expression of miR-200s was lost in PGI/AMF overexpressing MCF-10A cells and in highly invasive MDA-MB-231 cells, which was consistent with increased expression of ZEB1/ZEB2. Moreover, silencing of PGI/AMF expression in MDA-MB-231 cells led to overexpression of miR-200s, which was associated with reversal of EMT phenotype (i.e., mesenchymal-epithelial transition), and these findings were consistent with alterations in the relative expression of epithelial (E-cadherin) and mesenchymal (vimentin, ZEB1, ZEB2) markers and decreased aggressiveness as judged by clonogenic, motility, and invasion assays. Moreover, either reexpression of miR-200 or silencing of PGI/AMF suppressed pulmonary metastases of MDA-MB-231 cells in vivo, and anti-miR-200 treatment in vivo resulted in increased metastases. Collectively, these results suggest a role of miR-200s in PGI/AMF-induced EMT and thus approaches for upregulation of miR-200s could be a novel therapeutic strategy for the treatment of highly invasive breast cancer.

  11. A single amino acid change within the R2 domain of the VvMYB5b transcription factor modulates affinity for protein partners and target promoters selectivity

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    Granier Thierry

    2011-08-01

    Full Text Available Abstract Background Flavonoid pathway is spatially and temporally controlled during plant development and the transcriptional regulation of the structural genes is mostly orchestrated by a ternary protein complex that involves three classes of transcription factors (R2-R3-MYB, bHLH and WDR. In grapevine (Vitis vinifera L., several MYB transcription factors have been identified but the interactions with their putative bHLH partners to regulate specific branches of the flavonoid pathway are still poorly understood. Results In this work, we describe the effects of a single amino acid substitution (R69L located in the R2 domain of VvMYB5b and predicted to affect the formation of a salt bridge within the protein. The activity of the mutated protein (name VvMYB5bL, the native protein being referred as VvMYB5bR was assessed in different in vivo systems: yeast, grape cell suspensions, and tobacco. In the first two systems, VvMYB5bL exhibited a modified trans-activation capability. Moreover, using yeast two-hybrid assay, we demonstrated that modification of VvMYB5b transcriptional properties impaired its ability to correctly interact with VvMYC1, a grape bHLH protein. These results were further substantiated by overexpression of VvMYB5bR and VvMYB5bL genes in tobacco. Flowers from 35S::VvMYB5bL transgenic plants showed a distinct phenotype in comparison with 35S::VvMYB5bR and the control plants. Finally, significant differences in transcript abundance of flavonoid metabolism genes were observed along with variations in pigments accumulation. Conclusions Taken together, our findings indicate that VvMYB5bL is still able to bind DNA but the structural consequences linked to the mutation affect the capacity of the protein to activate the transcription of some flavonoid genes by modifying the interaction with its co-partner(s. In addition, this study underlines the importance of an internal salt bridge for protein conformation and thus for the establishment

  12. Growth factor TGF-β induces intestinal epithelial cell (IEC-6) differentiation: miR-146b as a regulatory component in the negative feedback loop.

    Science.gov (United States)

    Liao, Yalin; Zhang, Man; Lönnerdal, Bo

    2013-01-01

    TGF-β is a potent pleiotropic factor that promotes small intestinal cell differentiation. The role of microRNAs in the TGF-β induction of intestinal epithelial phenotype is largely unknown. We hypothesized that microRNAs are functionally involved in TGF-β-induced intestinal cell growth. In this study, TGF-β caused a morphological change of IEC-6 cells and stimulated expression of the epithelial cell markers alkaline phosphatase, villin, and aminopeptidase N. By global microRNA profiling during TGF-β-induced intestinal crypt cell (IEC-6) differentiation, we identified 19 differentially expressed microRNAs. We showed by real-time Q-PCR that miR-146b expression increased rapidly after TGF-β treatment; sequence analysis and in vitro assays revealed that miR-146b targets SIAH2, an E3 ubiquitin ligase, with decreased protein expression upon IEC-6 cell differentiation. Transfection of miR-146b inhibitor before TGF-β treatment blocked the down-regulation of SIAH2 in response to TGF-β. Moreover, SIAH2 over-expression during TGF-β treatment caused a significant decrease in Smad7 protein expression in IEC-6 cells. Furthermore, activation of the ERK1/2 pathway is active in the up-regulation of miR-146b by TGF-β. These findings suggest a novel mechanism whereby TGF-β signaling during IEC-6 cell differentiation may be modulated in part by microRNAs, and we propose a key role for miR-146b in the homeostasis of growth factor TGF-β signaling through a negative feedback regulation involving down-regulation of SIAH2 repressed Smad7 activities.

  13. AtMyb7, a subgroup 4 R2R3 Myb, negatively regulates ABA-induced inhibition of seed germination by blocking the expression of the bZIP transcription factor ABI5

    KAUST Repository

    Kim, Junhyeok

    2014-08-27

    Various Myb proteins have been shown to play crucial roles in plants, including primary and secondary metabolism, determination of cell fate and identity, regulation of development and involvement in responses to biotic and abiotic stresses. The 126 R2R3 Myb proteins (with two Myb repeats) have been found in Arabidopsis; however, the functions of most of these proteins remain to be fully elucidated. In the present study, we characterized the function of AtMyb7 using molecular biological and genetic analyses. We used qRT-PCR to determine the levels of stress-response gene transcripts in wild-type and atmyb7 plants. We showed that ArabidopsisAtMyb7 plays a critical role in seed germination. Under abscisic acid (ABA) and high-salt stress conditions, atmyb7 plants showed a lower germination rate than did wild-type plants. Furthermore, AtMyb7 promoter:GUS seeds exhibited different expression patterns in response to variations in the seed imbibition period. AtMyb7 negatively controls the expression of the gene encoding bZIP transcription factor, ABI5, which is a key transcription factor in ABA signalling and serves as a crucial regulator of germination inhibition in Arabidopsis. © 2014 John Wiley & Sons Ltd.

  14. The R2R3 MYB transcription factor PavMYB10.1 involves in anthocyanin biosynthesis and determines fruit skin colour in sweet cherry (Prunus avium L.).

    Science.gov (United States)

    Jin, Wanmei; Wang, Hua; Li, Maofu; Wang, Jing; Yang, Yuan; Zhang, Xiaoming; Yan, Guohua; Zhang, Hong; Liu, Jiashen; Zhang, Kaichun

    2016-11-01

    Sweet cherry is a diploid tree species and its fruit skin has rich colours from yellow to blush to dark red. The colour is closely related to anthocyanin biosynthesis and is mainly regulated at the transcriptional level by transcription factors that regulate the expression of multiple structural genes. However, the genetic and molecular bases of how these genes ultimately determine the fruit skin colour traits remain poorly understood. Here, our genetic and molecular evidences identified the R2R3 MYB transcription factor PavMYB10.1 that is involved in anthocyanin biosynthesis pathway and determines fruit skin colour in sweet cherry. Interestingly, we identified three functional alleles of the gene causally leading to the different colours at mature stage. Meanwhile, our experimental results of yeast two-hybrid assays and chromatin immunoprecipitation assays revealed that PavMYB10.1 might interact with proteins PavbHLH and PavWD40, and bind to the promoter regions of the anthocyanin biosynthesis genes PavANS and PavUFGT; these findings provided to a certain extent mechanistic insight into the gene's functions. Additionally, genetic and molecular evidences confirmed that PavMYB10.1 is a reliable DNA molecular marker to select fruit skin colour in sweet cherry.

  15. Rice osa-miR171c Mediates Phase Change from Vegetative to Reproductive Development and Shoot Apical Meristem Maintenance by Repressing Four OsHAM Transcription Factors.

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    Tian Fan

    Full Text Available Phase change from vegetative to reproductive development is one of the critical developmental steps in plants, and it is regulated by both environmental and endogenous factors. The maintenance of shoot apical meristem (SAM identity, miRNAs and flowering integrators are involved in this phase change process. Here, we report that the miRNA osa-miR171c targets four GRAS (GAI-RGA-SCR plant-specific transcription factors (OsHAM1, OsHAM2, OsHAM3, and OsHAM4 to control the floral transition and maintenance of SAM indeterminacy in rice (Oryza sativa. We characterized a rice T-DNA insertion delayed heading (dh mutant, where the expression of OsMIR171c gene is up-regulated. This mutant showed pleiotropic phenotypic defects, including especially prolonged vegetative phase, delayed heading date, and bigger shoot apex. Parallel expression analysis showed that osa-miR171c controlled the expression change of four OsHAMs in the shoot apex during floral transition, and responded to light. In the dh mutant, the expression of the juvenile-adult phase change negative regulator osa-miR156 was up-regulated, expression of the flowering integrators Hd3a and RFT1 was inhibited, and expression of FON4 negative regulators involved in the maintenance of SAM indeterminacy was also inhibited. From these data, we propose that the inhibition of osa-miR171c-mediated OsHAM transcription factors regulates the phase transition from vegetative to reproductive development by maintaining SAM indeterminacy and inhibiting flowering integrators.

  16. Assessment of Dysfunctional Cognitions in Binge-Eating Disorder: Factor Structure and Validity of the Mizes Anorectic Cognitions Questionnaire-Revised (MAC-R)

    Science.gov (United States)

    Carrard, Isabelle; Rothen, Stephane; Kruseman, Maaike; Khazaal, Yasser

    2017-01-01

    Background: Dysfunctional cognitions regarding weight and shape and their implications for self-esteem are considered core features of anorexia nervosa and bulimia nervosa. However, they have also been associated with the severity of binge eating disorder (BED). Therefore, they should be screened with appropriate instruments to tailor treatment to individual patient needs. The Mizes Anorectic Cognitions-Revised (MAC-R) is a self-report questionnaire that lists dysfunctional cognitions related to three hypothesized core beliefs typical of the psychopathology of eating disorders: weight and eating as the basis of approval from others; the belief that rigid self-control is fundamental to self-worth; and the rigidity of weight- and eating-regulation efforts. Objectives: The goal of the study was to confirm the factor structure and to assess the validity of the MAC-R among a sample that met full-threshold and subthreshold criteria for BED. Methods: We used data of women meeting full-threshold (n = 94) and subthreshold (n = 22) criteria for BED to conduct confirmatory factor analyses and to compute Spearman's correlations, in order to assess factorial, convergent, and discriminant validity. Results: Two models having a structure of three factors with or without a total score proved to be acceptable. The MAC-R total score was correlated with questionnaires assessing dimensions related to eating disorder psychopathology, adding to the validity of the questionnaire. Conclusion: These results were similar to those found in studies on the psychometric properties of the MAC among samples with anorexia nervosa or bulimia nervosa, encouraging the use of the MAC-R as a research or clinical tool in order to further document the core beliefs underlying BED. PMID:28261139

  17. Assessing the reliability and validity of the Revised Two Factor Study Process Questionnaire (R-SPQ2F in Ghanaian medical students

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    Victor Mogre

    2014-08-01

    Full Text Available Purpose: We investigated the validity and reliability of the Revised Two Factor Study Process Questionnaire (R-SPQ2F in preclinical students in Ghana. Methods: The R-SPQ2F was administered to 189 preclinical students of the University for Development Studies, School of Medicine and Health Sciences. Both descriptive and inferential statistics with Cronbach’s alpha test and factor analysis were done. Results: The mean age of the students was 22.69 ± 0.18 years, 60.8% (n = 115 were males and 42.3% (n = 80 were in their second year of medical training. The students had higher mean deep approach scores (31.23 ± 7.19 than that of surface approach scores (22.62 ± 6.48. Findings of the R-SPQ2F gave credence to a solution of two-factors indicating deep and surface approaches accounting for 49.80% and 33.57%, respectively, of the variance. The scales of deep approach (Cronbach’s alpha, 0.80 and surface approach (Cronbach’s alpha, 0.76 and their subscales demonstrated an internal consistency that was good. The factorial validity was comparable to other studies. Conclusion: Our study confirms the construct validity and internal consistency of the R-SPQ2F for measuring approaches to learning in Ghanaian preclinical students. Deep approach was the most dominant learning approach among the students. The questionnaire can be used to measure students’ approaches to learning in Ghana and in other African countries.

  18. Assessment of Dysfunctional Cognitions in Binge-Eating Disorder: Factor Structure and Validity of the Mizes Anorectic Cognitions Questionnaire-Revised (MAC-R).

    Science.gov (United States)

    Carrard, Isabelle; Rothen, Stephane; Kruseman, Maaike; Khazaal, Yasser

    2017-01-01

    Background: Dysfunctional cognitions regarding weight and shape and their implications for self-esteem are considered core features of anorexia nervosa and bulimia nervosa. However, they have also been associated with the severity of binge eating disorder (BED). Therefore, they should be screened with appropriate instruments to tailor treatment to individual patient needs. The Mizes Anorectic Cognitions-Revised (MAC-R) is a self-report questionnaire that lists dysfunctional cognitions related to three hypothesized core beliefs typical of the psychopathology of eating disorders: weight and eating as the basis of approval from others; the belief that rigid self-control is fundamental to self-worth; and the rigidity of weight- and eating-regulation efforts. Objectives: The goal of the study was to confirm the factor structure and to assess the validity of the MAC-R among a sample that met full-threshold and subthreshold criteria for BED. Methods: We used data of women meeting full-threshold (n = 94) and subthreshold (n = 22) criteria for BED to conduct confirmatory factor analyses and to compute Spearman's correlations, in order to assess factorial, convergent, and discriminant validity. Results: Two models having a structure of three factors with or without a total score proved to be acceptable. The MAC-R total score was correlated with questionnaires assessing dimensions related to eating disorder psychopathology, adding to the validity of the questionnaire. Conclusion: These results were similar to those found in studies on the psychometric properties of the MAC among samples with anorexia nervosa or bulimia nervosa, encouraging the use of the MAC-R as a research or clinical tool in order to further document the core beliefs underlying BED.

  19. A Community-Based Assessment of Hypertension and Some Other Cardiovascular Disease Risk Factors in Ngaoundéré, Cameroon

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    Olivier Pancha Mbouemboue

    2016-01-01

    Full Text Available Background and Objective. Cardiovascular diseases are primary causes of death worldwide with well documented risk factors whose varying impacts added to the complexity in CVD management dictate the need for region-specific studies. We aimed at investigating the interactions between CVD risk factors and hypertension in Ngaoundéré. Methods. A cross-sectional survey was carried out from March to August 2014. Sociodemographic, fasting blood glucose, blood pressure, and anthropometric data were recorded. Statistical analyses were carried out using SAS software version 9.1. Results. 700 adults resident in Ngaoundéré for at least two years consented and were included in the survey. Abdominal obesity, physical inactivity, and hypertension were the dominant risk factors recording 51.1%, 35.4%, and 20.4%, respectively. The prevalence of hyperglycaemia, tobacco consumption, obesity, and alcohol consumption was 5.6%, 8.3%, 9.6%, and 18.1%, respectively. Advanced age, hyperglycaemia, a divorced marital status, and alcohol consumption were independent determinants of high blood pressure. Conclusion. Physical inactivity, abdominal obesity, and hypertension were the most prevalent CVD risk factors, and the role of advanced age and hyperglycaemia in the occurrence of high blood pressure was reiterated. Health programs need to focus on effective screening, prevention, and control of CVDs in the Adamawa Region and Cameroon at large.

  20. Stimulation of Pol III-dependent 5S rRNA and U6 snRNA gene expression by AP-1 transcription factors.

    Science.gov (United States)

    Ahuja, Richa; Kumar, Vijay

    2017-07-01

    RNA polymerase III transcribes structurally diverse group of essential noncoding RNAs including 5S ribosomal RNA (5SrRNA) and U6 snRNA. These noncoding RNAs are involved in RNA processing and ribosome biogenesis, thus, coupling Pol III activity to the rate of protein synthesis, cell growth, and proliferation. Even though a few Pol II-associated transcription factors have been reported to participate in Pol III-dependent transcription, its activation by activator protein 1 (AP-1) factors, c-Fos and c-Jun, has remained unexplored. Here, we show that c-Fos and c-Jun bind to specific sites in the regulatory regions of 5S rRNA (type I) and U6 snRNA (type III) gene promoters and stimulate their transcription. Our chromatin immunoprecipitation studies suggested that endogenous AP-1 factors bind to their cognate promoter elements during the G1/S transition of cell cycle apparently synchronous with Pol III transcriptional activity. Furthermore, the interaction of c-Jun with histone acetyltransferase p300 promoted the recruitment of p300/CBP complex on the promoters and facilitated the occupancy of Pol III transcriptional machinery via histone acetylation and chromatin remodeling. The findings of our study, together, suggest that AP-1 factors are novel regulators of Pol III-driven 5S rRNA and U6 snRNA expression with a potential role in cell proliferation. © 2017 Federation of European Biochemical Societies.

  1. Tumor necrosis factor-α regulates glucocorticoid synthesis in the adrenal glands of Trypanosoma cruzi acutely-infected mice. the role of TNF-R1.

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    Silvina R Villar

    Full Text Available Adrenal steroidogenesis is under a complex regulation involving extrinsic and intrinsic adrenal factors. TNF-α is an inflammatory cytokine produced in response to tissue injury and several other stimuli. We have previously demonstrated that TNF-R1 knockout (TNF-R1(-/- mice have a dysregulated synthesis of glucocorticoids (GCs during Trypanosoma cruzi acute infection. Since TNF-α may influence GCs production, not only through the hypothalamus-pituitary axis, but also at the adrenal level, we now investigated the role of this cytokine on the adrenal GCs production. Wild type (WT and TNF-R1(-/- mice undergoing acute infection (Tc-WT and Tc-TNF-R1(-/- groups, displayed adrenal hyperplasia together with increased GCs levels. Notably, systemic ACTH remained unchanged in Tc-WT and Tc-TNF-R1(-/- compared with uninfected mice, suggesting some degree of ACTH-independence of GCs synthesis. TNF-α expression was increased within the adrenal gland from both infected mouse groups, with Tc-WT mice showing an augmented TNF-R1 expression. Tc-WT mice showed increased levels of P-p38 and P-ERK compared to uninfected WT animals, whereas Tc-TNF-R1(-/- mice had increased p38 and JNK phosphorylation respect to Tc-WT mice. Strikingly, adrenal NF-κB and AP-1 activation during infection was blunted in Tc-TNF-R1(-/- mice. The accumulation of mRNAs for steroidogenic acute regulatory protein and cytochrome P450 were significantly increased in both Tc-WT and Tc-TNF-R1(-/- mice; being much more augmented in the latter group, which also had remarkably increased GCs levels. TNF-α emerges as a potent modulator of steroidogenesis in adrenocortical cells during T. cruzi infection in which MAPK pathways, NF-κB and AP-1 seem to play a role in the adrenal synthesis of pro-inflammatory cytokines and enzymes regulating GCs synthesis. These results suggest the existence of an intrinsic immune-adrenal interaction involved in the dysregulated synthesis of GCs during murine Chagas

  2. Homeobox A9 directly targeted by miR-196b regulates aggressiveness through nuclear Factor-kappa B activity in non-small cell lung cancer cells.

    Science.gov (United States)

    Yu, Seong-Lan; Lee, Dong Chul; Sohn, Hyun Ahm; Lee, Soo Young; Jeon, Hyo Sung; Lee, Joon H; Park, Chang Gyo; Lee, Hoi Young; Yeom, Young Il; Son, Ji Woong; Yoon, Yoo Sang; Kang, Jaeku

    2016-12-01

    MicroRNAs (miRNAs) are recognized as crucial posttranscriptional regulators of gene expression, and play critical roles as oncogenes or tumor suppressors in various cancers. Here, we show that miR-196b is upregulated in mesenchymal-like-state non-small cell lung cancer (NSCLC) cells and lung cancer tissues. Moreover, miR-196b upregulation stimulates cell invasion and a change in cell morphology to a spindle shape via loss of cell-to-cell contacts. We identified homeobox A9 (HOXA9) as a target gene of miR-196b by using public databases such as TargetScan, miRDB, and microRNA.org. HOXA9 expression is inversely correlated with miR-196b levels in clinical NSCLC samples as compared to that in corresponding control samples, and with the migration and invasion of NSCLC cells. Ectopic expression of HOXA9 resulted in a suppression of miR-196b-induced cell invasion, and HOXA9 reexpression increased E-cadherin expression. Furthermore, HOXA9 potently attenuated the expression of snail family zinc finger 2 (SNAI2/SLUG) and matrix metallopeptidase 9 (MMP9) by controlling the binding of nuclear factor-kappa B to the promoter of SLUG and MMP9 genes, respectively. Therefore, we suggest that HOXA9 plays a central role in controlling the aggressive behavior of lung cancer cells and that miR-196b can serve as a potential target for developing anticancer agents. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  3. A connecter-like factor, CacA, links RssB/RpoS and the CpxR/CpxA two-component system in Salmonella

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    Kato Akinori

    2012-10-01

    Full Text Available Abstract Background Bacteria integrate numerous environmental stimuli when generating cellular responses. Increasing numbers of examples describe how one two-component system (TCS responds to signals detected by the sensor of another TCS. However, the molecular mechanisms underlying this phenomenon remain poorly defined. Results Here, we report a connector-like factor that affects the activity of the CpxR/CpxA two-component system in Salmonella enterica serovar Typhimurium. We isolated a clone that induced the expression of a cpxP-lac gene fusion from a high-copy-number plasmid pool of random Salmonella genomic fragments. A 63-amino acid protein, CacA, was responsible for the CpxA/CpxR-dependent activation of the cpxP gene. The CpxR-activated genes cpxP and spy exhibited approximately 30% and 50% reductions in transcription, respectively, in a clean cacA deletion mutant strain in comparison to wild-type. From 33 response regulator (RR deletion mutants, we identified that the RssB regulator represses cacA transcription. Substitution mutations in a conserved -10 region harboring the RNA polymerase recognition sequence, which is well conserved with a known RpoS -10 region consensus sequence, rendered the cacA promoter RpoS-independent. The CacA-mediated induction of cpxP transcription was affected in a trxA deletion mutant, which encodes thioredoxin 1, suggesting a role for cysteine thiol-disulfide exchange(s in CacA-dependent Cpx activation. Conclusions We identified CacA as an activator of the CpxR/CpxA system in the plasmid clone. We propose that CacA may integrate the regulatory status of RssB/RpoS into the CpxR/CpxA system. Future investigations are necessary to thoroughly elucidate how CacA activates the CpxR/CpxA system.

  4. A Conceptual Frame for Evaluating Success Factors being Critical for the Adaption of Externally Generated R&D

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    ARTURO RODRÍGUEZ CASTELLANOS

    2007-06-01

    Full Text Available Nowadays, enterprises require developing continuously innovations in their products, processes and organisational structures to gain and maintain competitive advantages. In this sense, the organizational adoption capacity of externally generated knowledge is becoming an increasingly crucial core capacity for businesses. Based on an empiric study, the present work proposes a model that aims at evaluating the organizational key drivers supporting the adoption of externally generated R+D. With this, it provides a management tool that might facilitate the determination of adequate strategies to take advantage of knowledge which is generated outide the own organizational borders.

  5. Search for limiting factors in the RNAi pathway in silkmoth tissues and the Bm5 cell line: the RNA-binding proteins R2D2 and Translin.

    Science.gov (United States)

    Swevers, Luc; Liu, Jisheng; Huvenne, Hanneke; Smagghe, Guy

    2011-01-01

    RNA interference (RNAi), an RNA-dependent gene silencing process that is initiated by double-stranded RNA (dsRNA) molecules, has been applied with variable success in lepidopteran insects, in contrast to the high efficiency achieved in the coleopteran Tribolium castaneum. To gain insight into the factors that determine the efficiency of RNAi, a survey was carried out to check the expression of factors that constitute the machinery of the small interfering RNA (siRNA) and microRNA (miRNA) pathways in different tissues and stages of the silkmoth, Bombyx mori. It was found that the dsRNA-binding protein R2D2, an essential component in the siRNA pathway in Drosophila, was expressed at minimal levels in silkmoth tissues. The silkmoth-derived Bm5 cell line was also deficient in expression of mRNA encoding full-length BmTranslin, an RNA-binding factor that has been shown to stimulate the efficiency of RNAi. However, despite the lack of expression of the RNA-binding proteins, silencing of a luciferase reporter gene was observed by co-transfection of luc dsRNA using a lipophilic reagent. In contrast, gene silencing was not detected when the cells were soaked in culture medium supplemented with dsRNA. The introduction of an expression construct for Tribolium R2D2 (TcR2D2) did not influence the potency of luc dsRNA to silence the luciferase reporter. Immunostaining experiments further showed that both TcR2D2 and BmTranslin accumulated at defined locations within the cytoplasm of transfected cells. Our results offer a first evaluation of the expression of the RNAi machinery in silkmoth tissues and Bm5 cells and provide evidence for a functional RNAi response to intracellular dsRNA in the absence of R2D2 and Translin. The failure of TcR2D2 to stimulate the intracellular RNAi pathway in Bombyx cells is discussed.

  6. Sensitivity of tensor analyzing power in the process d+p{r_arrow}d+X to the longitudinal isoscalar form factor of the Roper resonance electroexcitation

    Energy Technology Data Exchange (ETDEWEB)

    Tomasi-Gustafsson, E.; Rekalo, M.P. [DSM-CEA/IN2P3-CNRS, Laboratoire National Saturne, F-91191 Gif-sur-Yvette Cedex (France)]|[DAPNIA/SPhN, C.E.A./Saclay, F-91191 Gif-sur-Yvette Cedex (France); Bijker, R. [Instituto de Ciencias Nucleares, U.N.A.M., A.P. 70-543, 04510 Mexico Distrito Federal (Mexico); Leviatan, A. [Racah Institute of Physics, The Hebrew University, Jerusalem 91904 (Israel); Iachello, F. [Center for Theoretical Physics, Sloane Laboratory, Yale University, New Haven, Connecticut 06520-8120 (United States)

    1999-03-01

    The tensor analyzing power of the process d+p{r_arrow}d+X, for forward deuteron scattering in the momentum interval 3.7 to 9 GeV/c, is studied in the framework of {omega} exchange in an algebraic collective model for the electroexcitation of nucleon resonances. We point out a special sensitivity of the tensor analyzing power to the isoscalar longitudinal form factor of the Roper resonance excitation. The main argument is that the S{sub 11}(1535),thinspD{sub 13}(1520), and S{sub 11}(1650) resonances have only isovector longitudinal form factors. It is the longitudinal form factor of the Roper excitation, which plays an important role in the {ital t} dependence of the tensor analyzing power. We discuss possible evidence of swelling of hadrons with increasing excitation energy. {copyright} {ital 1999} {ital The American Physical Society}

  7. A Novel Association between Two Trypanosome-Specific Factors and the Conserved L5-5S rRNA Complex

    Science.gov (United States)

    Ciganda, Martin; Prohaska, Kimberly; Hellman, Kristina; Williams, Noreen

    2012-01-01

    P34 and P37 are two previously identified RNA binding proteins in the flagellate protozoan Trypanosoma brucei. RNA interference studies have determined that the proteins are involved in and essential for ribosome biogenesis. The proteins interact with the 5S rRNA with nearly identical binding characteristics. We have shown that this interaction is achieved mainly through the LoopA region of the RNA, but P34 and P37 also protect the L5 binding site located on LoopC. We now provide evidence to show that these factors form a novel pre-ribosomal particle through interactions with both 5S rRNA and the L5 ribosomal protein. Further in silico and in vitro analysis of T. brucei L5 indicates a lower affinity for 5S rRNA than expected, based on other eukaryotic L5 proteins. We hypothesize that P34 and P37 complement L5 and bridge the interaction with 5S rRNA, stabilizing it and aiding in the early steps of ribosome biogenesis. PMID:22859981

  8. A single mutation in the 15S rRNA gene confers nonsense suppressor activity and interacts with mRF1 the release factor in yeast mitochondria

    Directory of Open Access Journals (Sweden)

    Ali Gargouri

    2015-08-01

    Full Text Available We have determined the nucleotide sequence of the mim3-1 mitochondrial ribosomal suppressor, acting on ochre mitochondrial mutations and one frameshift mutation in Saccharomyces cerevisiae. The 15s rRNA suppressor gene contains a G633 to C transversion. Yeast mitochondrial G633 corresponds to G517 of the E.coli 15S rRNA, which is occupied by an invariant G in all known small rRNA sequences. Interestingly, this mutation has occurred at the same position as the known MSU1 mitochondrial suppressor which changes G633 to A. The suppressor mutation lies in a highly conserved region of the rRNA, known in E.coli as the 530-loop, interacting with the S4, S5 and S12 ribosomal proteins. We also show an interesting interaction between the mitochondrial mim3-1 and the nuclear nam3-1 suppressors, both of which have the same action spectrum on mitochondrial mutations: nam3-1 abolishes the suppressor effect when present with mim3-1 in the same haploid cell. We discuss these results in the light of the nature of Nam3, identified by [1] as the yeast mitochondrial translation release factor. A hypothetical mechanism of suppression by "ribosome shifting" is also discussed in view of the nature of mutations suppressed and not suppressed.

  9. Therapeutic applications of macrophage colony-stimulating factor-1 (CSF-1) and antagonists of CSF-1 receptor (CSF-1R) signaling.

    Science.gov (United States)

    Hume, David A; MacDonald, Kelli P A

    2012-02-23

    Macrophage-colony stimulating factor (CSF-1) signaling through its receptor (CSF-1R) promotes the differentiation of myeloid progenitors into heterogeneous populations of monocytes, macrophages, dendritic cells, and bone-resorbing osteoclasts. In the periphery, CSF-1 regulates the migration, proliferation, function, and survival of macrophages, which function at multiple levels within the innate and adaptive immune systems. Macrophage populations elicited by CSF-1 are associated with, and exacerbate, a broad spectrum of pathologies, including cancer, inflammation, and bone disease. Conversely, macrophages can also contribute to immunosuppression, disease resolution, and tissue repair. Recombinant CSF-1, antibodies against the ligand and the receptor, and specific inhibitors of CSF-1R kinase activity have been each been tested in a range of animal models and in some cases, in patients. This review examines the potential clinical uses of modulators of the CSF-1/CSF-1R system. We conclude that CSF-1 promotes a resident-type macrophage phenotype. As a treatment, CSF-1 has therapeutic potential in tissue repair. Conversely, inhibition of CSF-1R is unlikely to be effective in inflammatory disease but may have utility in cancer.

  10. A novel association between two trypanosome-specific factors and the conserved L5-5S rRNA complex.

    Directory of Open Access Journals (Sweden)

    Martin Ciganda

    Full Text Available P34 and P37 are two previously identified RNA binding proteins in the flagellate protozoan Trypanosoma brucei. RNA interference studies have determined that the proteins are involved in and essential for ribosome biogenesis. The proteins interact with the 5S rRNA with nearly identical binding characteristics. We have shown that this interaction is achieved mainly through the LoopA region of the RNA, but P34 and P37 also protect the L5 binding site located on LoopC. We now provide evidence to show that these factors form a novel pre-ribosomal particle through interactions with both 5S rRNA and the L5 ribosomal protein. Further in silico and in vitro analysis of T. brucei L5 indicates a lower affinity for 5S rRNA than expected, based on other eukaryotic L5 proteins. We hypothesize that P34 and P37 complement L5 and bridge the interaction with 5S rRNA, stabilizing it and aiding in the early steps of ribosome biogenesis.

  11. A novel association between two trypanosome-specific factors and the conserved L5-5S rRNA complex.

    Science.gov (United States)

    Ciganda, Martin; Prohaska, Kimberly; Hellman, Kristina; Williams, Noreen

    2012-01-01

    P34 and P37 are two previously identified RNA binding proteins in the flagellate protozoan Trypanosoma brucei. RNA interference studies have determined that the proteins are involved in and essential for ribosome biogenesis. The proteins interact with the 5S rRNA with nearly identical binding characteristics. We have shown that this interaction is achieved mainly through the LoopA region of the RNA, but P34 and P37 also protect the L5 binding site located on LoopC. We now provide evidence to show that these factors form a novel pre-ribosomal particle through interactions with both 5S rRNA and the L5 ribosomal protein. Further in silico and in vitro analysis of T. brucei L5 indicates a lower affinity for 5S rRNA than expected, based on other eukaryotic L5 proteins. We hypothesize that P34 and P37 complement L5 and bridge the interaction with 5S rRNA, stabilizing it and aiding in the early steps of ribosome biogenesis.

  12. rAAV-mediated delivery of brain-derived neurotrophic factor promotes neurite outgrowth and protects neurodegeneration in focal ischemic model.

    Science.gov (United States)

    Zhang, Jingyu; Yu, Zhigang; Yu, Zhiqiang; Yang, Zichao; Zhao, Hong; Liu, Luran; Zhao, Jiexu

    2011-06-20

    Stroke is one of the neurological diseases which lead to permanently neuronal damage after temporary or long-term occlusion of vessels or after heart attack. However, there are few efficient strategies to prevent or treat this kind of insult in clinical because the consequence is irreversible and could be long-lasting after the onset of stroke. Gene therapy especially using viral system has long been addressed to be of great potential to reduce the damage. Here, we generated recombinant adeno-associated virus (rAAV) carrying brain-derived neurotrophic factor (BDNF) gene. Cells infected with rAAV-BDNF could be able to produce functional BDNF which promoted neurite outgrowth and protected neurons from apoptosis induced by serum deprivation. Further more, single injection of rAAV showed neuroprotection against cell death in focal ischemic model. These results showed that rAAV-mediated gene delivery is functional, which shed light to the future application of viral system-based gene therapy in clinical.

  13. The ribosome biogenesis factor Nol11 is required for optimal rDNA transcription and craniofacial development in Xenopus.

    Directory of Open Access Journals (Sweden)

    John N Griffin

    2015-03-01

    Full Text Available The production of ribosomes is ubiquitous and fundamental to life. As such, it is surprising that defects in ribosome biogenesis underlie a growing number of symptomatically distinct inherited disorders, collectively called ribosomopathies. We previously determined that the nucleolar protein, NOL11, is essential for optimal pre-rRNA transcription and processing in human tissue culture cells. However, the role of NOL11 in the development of a multicellular organism remains unknown. Here, we reveal a critical function for NOL11 in vertebrate ribosome biogenesis and craniofacial development. Nol11 is strongly expressed in the developing cranial neural crest (CNC of both amphibians and mammals, and knockdown of Xenopus nol11 results in impaired pre-rRNA transcription and processing, increased apoptosis, and abnormal development of the craniofacial cartilages. Inhibition of p53 rescues this skeletal phenotype, but not the underlying ribosome biogenesis defect, demonstrating an evolutionarily conserved control mechanism through which ribosome-impaired craniofacial cells are removed. Excessive activation of this mechanism impairs craniofacial development. Together, our findings reveal a novel requirement for Nol11 in craniofacial development, present the first frog model of a ribosomopathy, and provide further insight into the clinically important relationship between specific ribosome biogenesis proteins and craniofacial cell survival.

  14. Systemic delivery of recombinant brain derived neurotrophic factor (BDNF) in the R6/2 mouse model of Huntington's disease.

    Science.gov (United States)

    Giampà, Carmela; Montagna, Elena; Dato, Clemente; Melone, Mariarosa A B; Bernardi, Giorgio; Fusco, Francesca Romana

    2013-01-01

    Loss of huntingtin-mediated BDNF gene transcription has been shown to occur in HD and thus contribute to the degeneration of the striatum. Several studies have indicated that an increase in BDNF levels is associated with neuroprotection and amelioration of neurological signs in animal models of HD. In a recent study, an increase in BDNF mRNA and protein levels was recorded in mice administered recombinant BDNF peripherally. Chronic, indwelling osmotic mini-pumps containing either recombinant BDNF or saline were surgically placed in R6/2 or wild-type mice from 4 weeks of age until euthanasia. Neurological evaluation (paw clasping, rotarod performance, locomotor activity in an open field) was performed. After transcardial perfusion, histological and immunohistochemical studies were performed. We found that BDNF- treated R6/2 mice survived longer and displayed less severe signs of neurological dysfunction than the vehicle treated ones. Primary outcome measures such as brain volume, striatal atrophy, size and morphology of striatal neurons, neuronal intranuclear inclusions and microglial reaction confirmed a neuroprotective effect of the compound. BDNF was effective in increasing significantly the levels of activated CREB and of BDNF the striatal spiny neurons. Moreover, systemically administered BDNF increased the synthesis of BDNF as demonstrated by RT-PCR, and this might account for the beneficial effects observed in this model.

  15. Dual control of Sinorhizobium meliloti RpoE2 sigma factor activity by two PhyR-type two-component response regulators.

    Science.gov (United States)

    Bastiat, Bénédicte; Sauviac, Laurent; Bruand, Claude

    2010-04-01

    RpoE2 is an extracytoplasmic function (ECF) sigma factor involved in the general stress response of Sinorhizobium meliloti, the nitrogen-fixing symbiont of the legume plant alfalfa. RpoE2 orthologues are widely found among alphaproteobacteria, where they play various roles in stress resistance and/or host colonization. In this paper, we report a genetic and biochemical investigation of the mechanisms of signal transduction leading to S. meliloti RpoE2 activation in response to stress. We showed that RpoE2 activity is negatively controlled by two paralogous anti-sigma factors, RsiA1 (SMc01505) and RsiA2 (SMc04884), and that RpoE2 activation by stress requires two redundant paralogous PhyR-type response regulators, RsiB1 (SMc01504) and RsiB2 (SMc00794). RsiB1 and RsiB2 do not act at the level of rpoE2 transcription but instead interact with the anti-sigma factors, and we therefore propose that they act as anti-anti-sigma factors to relieve RpoE2 inhibition in response to stress. This model closely resembles a recently proposed model of activation of RpoE2-like sigma factors in Methylobacterium extorquens and Bradyrhizobium japonicum, but the existence of two pairs of anti- and anti-anti-sigma factors in S. meliloti adds an unexpected level of complexity, which may allow the regulatory system to integrate multiple stimuli.

  16. R\\^ole of the pion electromagnetic form factor in the $\\Delta(1232) \\to \\gamma^\\ast N$ timelike transition

    CERN Document Server

    Ramalho, G; Weil, J; van Hees, H; Mosel, U

    2015-01-01

    The $\\Delta(1232) \\to \\gamma^\\ast N$ magnetic dipole form factor ($G_M^\\ast$) is described here within a new covariant model that combines the valence quark core together with the pion cloud contributions. The pion cloud term is parameterized by two terms: one connected to the pion electromagnetic form factor, the other to the photon interaction with intermediate baryon states. The model can be used in studies of pp and heavy ion collisions. In the timelike region this new model improves the results obtained with a constant form factor model fixed at its value at zero momentum transfer. At the same time, and in contrast to the Iachello model, this new model predicts a peak for the transition form factor at the expected position, i.e. at the $\\rho$ mass pole. We calculate the decay of the $\\Delta \\to \\gamma N$ transition, the Dalitz decay ($\\Delta \\to e^+ e^- N$), and the $\\Delta$ mass distribution function. The impact of the model on dilepton spectra in pp collisions is also discussed.

  17. Multiple-Group Confirmatory Factor Analysis in R--A Tutorial in Measurement Invariance with Continuous and Ordinal Indicators

    Science.gov (United States)

    Hirschfeld, Gerrit; von Brachel, Ruth

    2014-01-01

    Multiple-group confirmatory factor analysis (MG-CFA) is among the most productive extensions of structural equation modeling. Many researchers conducting cross-cultural or longitudinal studies are interested in testing for measurement and structural invariance. The aim of the present paper is to provide a tutorial in MG-CFA using the freely…

  18. The tRNA synthetase paralog PoxA modifies elongation factor-P with (R)-ß-lysine

    DEFF Research Database (Denmark)

    Roy, Hervé; Zou, S Betty; Bullwinkle, Tammy J

    2011-01-01

    The lysyl-tRNA synthetase paralog PoxA modifies elongation factor P (EF-P) with a-lysine at low efficiency. Cell-free extracts containing non-a-lysine substrates of PoxA modified EF-P with a change in mass consistent with addition of ß-lysine, a substrate also predicted by genomic analyses. EF-P ...

  19. Research on Transport System Risk Factors of Open-pit Mine Based on W-R-SHEL%基于W-R-SHEL的露天矿山运输系统风险因素研究

    Institute of Scientific and Technical Information of China (English)

    姜立春; 任晓会

    2011-01-01

    Personnel, machinery, environment, management and other aspects are related with Open-pit mine transport system accident. According to the fact that Open-pit mine transport system is complex and has high accident rate, human factors are chosen as the focus of risk factors analysis, a new risk factors I-dentification model is proposed based on the combination of WBS and R-SHEL model. With this model, risk factors of a large domestic aluminum mine' 8 transport system were identified, five first-level indexes, thirteen second-level indexes, forty third-level indexes were determined, risk factors'comprehensive evaluation was achieved by using three -scale IAHP and fuzzy mathematics, the comprehensive evaluation results are consistent with the practical situation.%露天矿山运输系统事故原因涉及人、机、环、管等多个环节.基于运输系统复杂、高事故率这一实际情况,以人为因素作为风险因素的分析中心,在总结传统人为风险因素辨识模型存在不足的基础上,提出基于工作分解结构(WBS)与R-SHEL相结合的风险因素辨识模型.将模型具体应用在国内某大型铝土矿山运输系统风险因素研究中,确定5个一级因素指标、13个二级因素指标及40个三级因素指标,采用三级标度IAHP与模糊(fuzzy)相结合的方法实现指标体系中风险因素的综合评判,得出综合评判结果与现场实际情况基本相符.

  20. The three factor eating questionnaire - R21: tradução para o português e aplicação em mulheres brasileiras The three factor eating questionnaire - R21: translation and administration to Brazilian women

    Directory of Open Access Journals (Sweden)

    Lara Cristiane Natacci

    2011-06-01

    Full Text Available OBJETIVO: Analisar e discutir a relação dos comportamentos de restrição cognitiva, alimentação emocional e descontrole alimentar entre si e com os parâmetros antropométricos: índice de massa corporal e circunferência abdominal. MÉTODOS: Tradução para o português e aplicação do The Three Factor Eating Questionnaire - versão reduzida de 21 itens, com subsequente comparação aos parâmetros antropométricos de 125 mulheres trabalhadoras do Instituto Central do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, escolhidas casualmente em um grupo de 800 interessados em orientação nutricional. RESULTADOS: Encontraram-se associações entre a alimentação emocional e o descontrole alimentar, além de associações entre alimentação emocional e descontrole alimentar, índice de massa corporal e circunferência abdominal. CONCLUSÃO: O The Three Factor Eating Questionnaire - versão reduzida de 21 itens mostrou-se um instrumento adequado para identificar os comportamentos de restrição cognitiva, alimentação emocional e descontrole alimentar, padrões de comportamentos cuja análise pode servir como ponto de partida para a adoção de estratégias de abordagem de orientação nutricional em programas de controle de peso.OBJECTIVE: This study analyzed and discussed how cognitive restraint, emotional eating and bingeing behaviors interrelate and relate with the anthropometric parameters BMI and waist circumference. METHODS: The short version of The Three Factor Eating Questionnaire consisting of 21 items was translated into Portuguese, administered to 125 female employees from the Central Unit of the Universidade de São Paulo School of Medicine Clinics Hospital and compared with the anthropometric data of these women who had been casually selected from a group of 800 individuals interested in nutrition counseling. RESULTS: Emotional eating was found to be associated with bingeing, body mass index and

  1. The Effect of Technological and Organizational Factors on Knowledge Sharing in National Library and Archives of I.R of Iran

    Directory of Open Access Journals (Sweden)

    Shabnam Refoua

    2015-12-01

    Full Text Available The effect of technological and organizational factors on knowledge sharing in National Library and Archives of I.R of Iran have been studied in the current study. It is considered as "applied" and "descriptive-survey" study based on its objects and data collection method accordingly.The research population consists of the educated librarians of National Library and Archives including four sectors of collecting, organizing, informing and R&D. After the data collection via questionnaire, structural equations have been used to test the research hypothesis. The Results indicated that the organizational climate, and structure, information and communication support have positive and meaningful effects on the knowledge sharing. The Results gained on testing the secondary hypothesis indicated that centralization, manager’s attitude, information and communication usage, reward system, organizational learning have positive and meaningful effects on the knowledge sharing

  2. Form factor ratio measurement in {Lambda}{sup +}{sub {ital c}}{r_arrow}{Lambda}{ital e}{sup +}{nu}{sub {ital e}}

    Energy Technology Data Exchange (ETDEWEB)

    Crawford, G.; Daubenmier, C.M.; Fulton, R.; Fujino, D.; Gan, K.K.; Honscheid, K.; Kagan, H.; Kass, R.; Lee, J.; Sung, M.; White, C.; Wolf, A.; Zoeller, M.M.; Butler, F.; Fu, X.; Nemati, B.; Ross, W.R.; Skubic, P.; Wood, M.; Bishai, M.; Fast, J.; Gerndt, E.; Hinson, J.W.; McIlwain, R.L.; Miao, T.; Miller, D.H.; Modesitt, M.; Payne, D.; Shibata, E.I.; Shipsey, I.P.J.; Wang, P.N.; Battle, M.; Ernst, J.; Gibbons, L.; Kwon, Y.; Roberts, S.; Thorndike, E.H.; Wang, C.H.; Dominick, J.; Lambrecht, M.; Sanghera, S.; Shelkov, V.; Skwarnicki, T.; Stroynowski, R.; Volobouev, I.; Wei, G.; Zadorozhny, P.; Artuso, M.; Gao, M.; Goldberg, M.; He, D.; Horwitz, N.; Moneti, G.C.; Mountain, R.; Muheim, F.; Mukhin, Y.; Playfer, S.; Rozen, Y.; Stone, S.; Xing, X.; Zhu, G.; Bartelt, J.; Csorna, S.E.; Egyed, Z.; Jain, V.; Gibaut, D.; Kinoshita, K.; Pomianowski, P.; Barish, B.; Chadha, M.; Chan, S.; Cowen, D.F.; Eigen, G.; Miller, J.S.; O`Grady, C.; Urheim, J.; Weinstein, A.J.; Athanas, M.; Brower, W.; Masek, G.; Paar, H.P.; Gronberg, J.; Korte, C.M.; Kutschke, R.; Menary, S.; Morrison, R.J.; Nakanishi, S.; Nelson, H.N.; Nelson, T.K.; Qiao, C.; Richman, J.D.; Ryd, A.; Sperka, D.; Tajima, H.; Witherell, M.S.; Procario, M.; Balest, R.; Cho, K.; Ford, W.T.; Johnson, D.R.; Lingel, K.; Lohner, M.; Rankin, P.; Smith, J.G.; Alexander, J.P.; Bebek, C.; Berkelman, K.; Bloom, K.; Browder, T.E.; Cassel, D.G.; Cho, H.A.; Coffman, D.M.; Crowcroft, D.S.; Drell, P.S.; Dumas, D.J.; Ehrlich, R.; Gaidarev, P.; Garcia-Sciveres, M.; Geiser, B.; Gittelman, B.; Gray, S.W.; Hartill, D.L.; Heltsley, B.K.; Henderson, S.; Jones, C.D.; Jones, S.L.; Kandaswamy, J.; Katayama, N.; Kim, P.C.; Kreinick, D.L.; Ludwig, G.S.; Masui, J.; Mevissen, J.; Mistry, N.B.; Ng, C.R.; Nordberg, E.; Patterson, J.R.; Peterson, D.; Riley, D.; Salman, S.; Sapper, M.; Wuerthwein, F.; Avery, P.; Freyberger, A.; Rodriguez, J.; Yang, S.; Yelton, J.; Cinabro, D.; Liu, T.; Saulnier, M.; Wilson, R.; Yamamoto, H.; Bergfeld, T.; (CLEO Collaboration)

    1995-07-24

    The angular distributions of the decay {Lambda}{sup +}{sub {ital c}}{r_arrow}{Lambda}{ital e}{sup +}{nu}{sub {ital e}} have been studied using the CLEO II detector. By performing a three-dimensional maximum likelihood fit, the form factor ratio {ital R}={ital f}{sub 2}/{ital f}{sub 1} is determined to be {minus}0.25{plus_minus}0.14{plus_minus}0.08. The decay asymmetry parameter of the {Lambda}{sub {ital c}} averaged over {ital q}{sup 2} is calculated to be {alpha}{sub {Lambda}{sub {ital c}}}={minus}0.82{sub {minus}0.06{minus}0.03}{sup +0.09+0.06}.

  3. Downregulation of transcription factor aflR in Aspergillus flavus confers reduction to aflatoxin accumulation in transgenic maize with alteration of host plant architecture.

    Science.gov (United States)

    Masanga, Joel Okoyo; Matheka, Jonathan Mutie; Omer, Rasha Adam; Ommeh, Sheila Cecily; Monda, Ethel Oranga; Alakonya, Amos Emitati

    2015-08-01

    We report success of host-induced gene silencing in downregulation of aflatoxin biosynthesis in Aspergillus flavus infecting maize transformed with a hairpin construct targeting transcription factor aflR. Infestation of crops by aflatoxin-producing fungi results in economic losses as well as negative human and animal health effects. Currently, the control strategies against aflatoxin accumulation are not effective to the small holder farming systems in Africa and this has led to widespread aflatoxin exposure especially in rural populations of sub-Saharan Africa that rely on maize as a staple food crop. A recent strategy called host-induced gene silencing holds great potential for developing aflatoxin-resistant plant germplasm for the African context where farmers are unable to make further investments other than access to the germplasm. We transformed maize with a hairpin construct targeting the aflatoxin biosynthesis transcription factor aflR. The developed transgenic maize were challenged with an aflatoxigenic Aspergillus flavus strain from Eastern Kenya, a region endemic to aflatoxin outbreaks. Our results indicated that aflR was downregulated in A. flavus colonizing transgenic maize. Further, maize kernels from transgenic plants accumulated significantly lower levels of aflatoxins (14-fold) than those from wild type plants. Interestingly, we observed that our silencing cassette caused stunting and reduced kernel placement in the transgenic maize. This could have been due to "off-target" silencing of unintended genes in transformed plants by aflR siRNAs. Overall, this work indicates that host-induced gene silencing has potential in developing aflatoxin-resistant germplasm.

  4. NMR structure of rALF-Pm3, an anti-lipopolysaccharide factor from shrimp: model of the possible lipid A-binding site.

    Science.gov (United States)

    Yang, Yinshan; Boze, Hélène; Chemardin, Patrick; Padilla, André; Moulin, Guy; Tassanakajon, Anchalee; Pugnière, Martine; Roquet, Françoise; Destoumieux-Garzón, Delphine; Gueguen, Yannick; Bachère, Evelyne; Aumelas, André

    2009-03-01

    The anti-lipopolysaccharide factor ALF-Pm3 is a 98-residue protein identified in hemocytes from the black tiger shrimp Penaeus monodon. It was expressed in Pichia pastoris from the constitutive glyceraldehyde-3-phosphate dehydrogenase promoter as a folded and (15)N uniformly labeled rALF-Pm3 protein. Its 3D structure was established by NMR and consists of three alpha-helices packed against a four-stranded beta-sheet. The C(34)-C(55) disulfide bond was shown to be essential for the structure stability. By using surface plasmon resonance, we demonstrated that rALF-Pm3 binds to LPS, lipid A and to OM-174, a soluble analogue of lipid A. Biophysical studies of rALF-Pm3/LPS and rALF-Pm3/OM-174 complexes indicated rather high molecular sized aggregates, which prevented us to experimentally determine by NMR the binding mode of these lipids to rALF-Pm3. However, on the basis of striking structural similarities to the FhuA/LPS complex, we designed an original model of the possible lipid A-binding site of ALF-Pm3. Such a binding site, located on the ALF-Pm3 beta-sheet and involving seven charged residues, is well conserved in ALF-L from Limulus polyphemus and in ALF-T from Tachypleus tridentatus. In addition, our model is in agreement with experiments showing that beta-hairpin synthetic peptides corresponding to ALF-L beta-sheet bind to LPS. Delineating lipid A-binding site of ALFs will help go further in the de novo design of new antibacterial or LPS-neutralizing drugs.

  5. NMR Structure of rALF-Pm3, an Anti-Lipopolysaccharide Factor from Shrimp: Model of the Possible Lipid A-Binding Site

    OpenAIRE

    Yang, Yinshan; Boze, Helene; Chemardin, Patrick; Padilla, Andre; Moulin, Guy; Tassanakajon, Anchalee; Pugniere, Martine; Roquet, Francoise; Destoumieux Garzon, Delphine; Gueguen, Yannick; Bachere, Evelyne; Aumelas, Andre

    2009-01-01

    The anti-lipopolysaccharide factor ALF-Pm3 is a 98-residue protein identified in hemocytes from the black tiger shrimp Penaeus monodon. It was expressed in Pichia pastoris from the constitutive glyceraldehyde-3-phosphate dehydrogenase promoter as a folded and N-15 uniformly labeled rALF-Pm3 protein. Its 3D structure was established by NMR and consists of three alpha-helices packed against a four-stranded beta-sheet. The C-34-C-55 disulfide bond was shown to be essential for the structure stab...

  6. SAR and X-ray Structures of Enantiopure 1,2-cis-(1R,2S)-cyclopentyldiamine and Cyclohexyldiamine Derivativies as Inhibitors of Coagulation Factor Xa

    Energy Technology Data Exchange (ETDEWEB)

    Qiao,J.; Chang, C.; Cheney, D.; Morin, D.; Wang, P.; King, G.; Wang, S.; Rendina, T.; Luettgen, A.; et al.

    2007-01-01

    In the search of Factor Xa (FXa) inhibitors structurally different from the pyrazole-based series, we identified a viable series of enantiopure cis-(1R,2S)-cycloalkyldiamine derivatives as potent and selective inhibitors of FXa. Among them, cyclohexyldiamide 7 and cyclopentyldiamide 9 were the most potent neutral compounds, and had good anticoagulant activity comparable to the pyrazole-based analogs. Crystal structures of 7-FXa and 9-FXa illustrate binding similarities and differences between the five- and the six-membered core systems, and provide rationales for the observed SAR of P1 and linker moieties.

  7. Anti-inflammatory effects of tumour necrosis factor (TNF)-alpha are mediated via TNF-R2 (p75) in tolerogenic transforming growth factor-beta-treated antigen-presenting cells.

    Science.gov (United States)

    Masli, Sharmila; Turpie, Bruce

    2009-05-01

    Exposure of macrophages to transforming growth factor (TGF)-beta is known to alter their functional phenotype such that antigen presentation by these cells leads to tolerance rather than an inflammatory immune response. Typically, eye-derived antigen-presenting cells (APCs) exposed to TGF-beta in the local environment are known to induce a form of peripheral tolerance and protect the eye from inflammatory immune effector-mediated damage. In response to TGF-beta, APCs increase their expression of tumour necrosis factor (TNF)-alpha and TNF receptor 2 (TNF-R2). Although TNF-alpha has been implicated in tolerance and the associated regulation of the inflammatory immune response, its source and the receptors involved remain unclear. In this report we determined the contribution of TNF-alpha and TNF-R2 expressed by TGF-beta-treated APCs to their anti-inflammatory tolerogenic effect. Our results indicate that APC-derived TNF-alpha is essential for the ability of APCs to regulate the immune response and their IL-12 secretion. Moreover, in the absence of TNF-R2, APCs exposed to TGF-beta failed to induce tolerance or regulatory cells known to participate in this tolerance. Also, blocking of TNF-R1 signalling enhanced the ability of the APCs to secrete increased TGF-beta in response to TGF-beta exposure. Together our results support an anti-inflammatory role of TNF-alpha in regulation of an immune response by TGF-beta-treated APCs and suggest that TNF-R2 contributes significantly to this role.

  8. Fusion of gelonin and anti-insulin-like growth factor-1 receptor (IGF-1R) affibody for enhanced brain cancer therapy.

    Science.gov (United States)

    Ham, Songhee; Min, Kyoung Ah; Yang, Jae Wook; Shin, Meong Cheol

    2017-09-12

    Owing to the extraordinary potency in inhibiting protein translation that could eventually lead to apoptosis of tumor cells, ribosome-inactivating proteins (RIPs) such as gelonin have been considered attractive drug candidates for cancer therapy. However, due to several critical obstacles (e.g., severe toxicity issues caused by a lack of selectivity in their mode of action and the low cytotoxicity via poor cellular uptake, etc.), clinical application of RIPs is yet far from being accomplished. To overcome these challenges, in the present study, we engineered gelonin fusion proteins with anti-insulin-like growth factor-1 receptor (IGF-1R) affibody ("IAFF") via the genetic recombinant method and the SpyCatcher/SpyTag-mediated conjugation method. To this end, recombinant gelonin-anti-IGF-1R affibody (rGel-IAFF), gelonin-SpyCatcher (Gel-SpyCatcher) and SpyTag-IAFF fusion proteins were produced from the E. coli expression system, and gelonin-IAFF conjugate was synthesized by mixing Gel-SpyCatcher and SpyTag-IAFF. After preparation of both rGel-IAFF and Gel-IAFF conjugate, their components' functionality was characterized in vitro. Our assay results confirmed that, while both Gel-IAFF and Gel-SpyCatcher retained equipotent N-glycosidase activity to that of gelonin, IAFF was able to selectively bind to IGF-1R overexpressed U87 MG brain cancer cells over low expression LNCaP cells. The results of cellular analyses showed that rGel-IAFF and Gel-IAFF conjugate both exhibited a greater cell uptake in the U87 MG cells than gelonin, but not in the LNCaP cells, yielding a significantly augmented cytotoxicity only in the U87 MG cells. Remarkably, rGel-IAFF and Gel-IAFF conjugate displayed 22- and 5.6-fold lower IC50 values (avg. IC50: 180 and 720 nM, respectively) than gelonin (avg. IC50: 4000 nM) in the U87 MG cells. Overall, the results of the present research demonstrated that fusion of gelonin with IAFF could provide an effective way to enhance the anti-tumor activity

  9. Paget-Schroetter syndrome after a dental procedure in a patient with factor V Leiden (R506Q) heterozygosity.

    Science.gov (United States)

    Sharma, Prabin

    2017-04-01

    : Paget-Schroetter syndrome or effort thrombosis is characterized by spontaneous thrombosis of the upper extremity venous system, commonly seen in a young healthy patient after repetitive use of the upper extremities. It is rarely associated with coagulopathy and thus, hypercoagulable work-up is not usually a part of the investigation. We present a first case of a young woman, who was diagnosed with left upper extremity effort thrombosis following a dental procedure. Interestingly, she was also noted to be heterozygous for factor V Leiden mutation.

  10. Role of certain environmental factors on cadmium uptake and toxicity in Spirodela polyrhiza (L.) Schleid. and Azolla pinnata R. Br.

    Science.gov (United States)

    Gaur, J P; Noraho, N

    1995-09-01

    Effects of pH, temperature, EDTA and photosynthetically available radiation on the uptake and toxicity of Cd was investigated in Spirodela polyrhiza (L.) Schleid. and Azolla pinnata R. Br. In general, Cd toxicity was accentuated in conditions which favoured enhanced intracellular Cd uptake. Extracellular binding and intracellular uptake of Cd were lowered at pH values > 7 due to reduced availability of the aquo ion; consequently, toxicity was markedly reduced. At pH value 99%) remains available as the aquo ion. The presence of EDTA in the medium decreased extracellular binding, intracellular uptake and toxicity of Cd in test plants. This was due to formation of Cd-EDTA complex which was obviously not available to test plants. Elevation of temperature increased intracellular Cd uptake and this resulted in enhanced toxic effects. Similarly, increase in photosynthetically available radiation caused a slight increase in Cd uptake and toxicity in test plants. Obviously, rise in temperature or PAR increased metabolic activities of test plants thereby leading to increased Cd transport and toxicity.

  11. Activation energy and R. Chen frequency factor in the Randall and Wilkins original equation for second order kinetics. Emission curve simulated in Microsoft Excel algebra; Energia de activacion y factor de frecuencia de R. Chen en la ecuacion original de Randall y Wilkins para cinetica de segundo orden. Curva de emision simulada en algebra de Microsoft Excel

    Energy Technology Data Exchange (ETDEWEB)

    Moreno M, A. [Departamento de Apoyo en Ciencias Aplicadas, Benemerita Universidad Autonoma de Puebla, 4 Sur 104, Centro Historico, 72000 Puebla (Mexico); Moreno B, A

    2000-07-01

    In this work the incorporation of activation energy and frequency factor parameters proposed by R. Chen are presented in the original formulation of Randall and wilkins second order kinetics. The results concordance are compared between the calculus following the R. Chen methodology with those ones obtained by direct incorporation of the previously indicated in the Randall-Wilkins-Levy expression for a simulated thermoluminescent emission curve of two peaks with maximum peak temperature (tm): t m1=120 and t m2=190. (Author)

  12. 企业R & D投入影响因素及其经济效果研究评述%A Review of the Influencing Factors and Economic Effect of Enterprise R & D Investment

    Institute of Scientific and Technical Information of China (English)

    张俊瑞; 刘彬; 程子健

    2013-01-01

    In the era of knowledge economy, the creation of firm value and the economical development of regions and nations rely more on the scientific and technological innovation. The R&D investment of enterprises is not only an important measure of the competitive pow-er of enterprises and their capacity for sustainable development, but also a main embodiment of the industrial competitiveness and the inno-vation capacity for all countries. By summarizing the existing literature on R&D investment, this paper builds a research framework as fol-lowing:on the one hand, both the internal and external conditions of a firm are important factors that can affect the investment amount and efficiency of R&D activities;on the other hand, the amount and efficiency of R&D investment can exert an important impact on firm value creation and growth, and therefore influence the sustainable development of regional and national economy.%在知识经济时代,企业的价值创造与其所在地区乃至国家的经济发展,越来越依赖于科技创新与进步。企业研发投入水平是衡量企业竞争能力和可持续发展能力的重要指标,也是各国产业竞争力和创新能力的重要体现。通过对现有文献的归纳,梳理出如下研究线索与框架:企业内外部条件是决定企业研发投入水平与效率的重要因素,而企业自身的研发投入与研发效率则会对其价值创造与成长产生影响,并进一步影响该地区乃至国家经济的可持续发展。

  13. Recombinant factor C (rFC) assay and gas chromatography/mass spectrometry (GC/MS) analysis of endotoxin variability in four agricultural dusts.

    Science.gov (United States)

    Saito, Rena; Cranmer, Brian K; Tessari, John D; Larsson, Lennart; Mehaffy, John M; Keefe, Thomas J; Reynolds, Stephen J

    2009-10-01

    Endotoxin exposure is a significant concern in agricultural environments due to relatively high exposure levels. The goals of this study were to determine patterns of 3-hydroxy fatty acid (3-OHFA) distribution in dusts from four types of agricultural environments (dairy, cattle feedlot, grain elevator, and corn farm) and to evaluate correlations between the results of gas chromatography/mass spectrometry (GC/MS) analysis (total endotoxin) and biological recombinant factor C (rFC) assay (free bioactive endotoxin). An existing GC/MS-MS method (for house dust) was modified to reduce sample handling and optimized for small amount (rFC assay and the modified GC/EI-MS results was feedlot (0.72) > dairy (0.53) > corn farm (0.33) > grain elevator (0.11). In livestock environments, both odd- and even-numbered carbon chain length 3-OHFAs correlated with rFC assay response. The GC/EI-MS method should be especially useful for identification of specific 3-OHFAs for endotoxins from various agricultural environments and may provide useful information for evaluating the relationship between bacterial exposure and respiratory disease among agricultural workers.

  14. Relative importance of fluorescent siderophores and other factors in biological control of Gaeumannomyces graminis var. tritici by Pseudomonas fluorescens 2-79 and M4-80R.

    Science.gov (United States)

    Hamdan, H; Weller, D M; Thomashow, L S

    1991-11-01

    Pseudomonas fluorescens 2-79 suppresses take-all, a major root disease of wheat caused by Gaeumannomyces graminis var. tritici. The bacteria produce an antibiotic, phenazine-1-carboxylic acid (PCA), and a fluorescent pyoverdin siderophore. Previous studies have established that PCA has an important role in the biological control of take-all but that antibiotic production does not account fully for the suppressiveness of the strain. To define the role of the pyoverdin siderophore more precisely, mutants deficient in production of the antibiotic, the siderophore, or both factors were constructed and compared with the parental strain for control of take-all on wheat roots. In all cases, strains that produced PCA were more suppressive than those that did not, and pyoverdin-deficient mutant derivatives controlled take-all as effectively as their respective fluorescent parental strains. Thus, the phenazine antibiotic was the dominant factor in disease suppression and the fluorescent siderophore had little or no role. The siderophore also was of minor importance in a second strain, P. fluorescens M4-80R, that does not produce PCA. Strains 2-79 and M4-80R both produced substances distinct from the pyoverdin siderophore that were responsible for fungal inhibition in vitro under iron limitation, but these substances also had, at most, a minor role in disease suppression in situ.

  15. Identification of Factors Affecting the Level of Consumer Satisfaction in Thermal Tourism Business: An Application on Kırşehir

    Directory of Open Access Journals (Sweden)

    Burcu Gülsevil Belber

    2015-09-01

    Full Text Available In this study, it was mentioned the situation of thermal tourism in Turkey and in the world, Turkey’s geothermal potential and utilization of the thermal tourism, the characteristics of the thermal waters and benefits in terms of health, activities related to the subject of the tourism ministry, elements of the marketing mix in the thermal plant, the status of the thermalplant in Kırşehir, a research about determining the level of satisfaction of the consumer who staying in thermal plants. Research was conducted by applying the survey methods to the tourist consumer accommodate in thermal plants. It has been demonstrated the factors affecting the level of satisfaction of participants by the agency of factor analysis and MANOVA analysis were made for the purpose ofresearch and were determined whether if they show changes according to demographic characteristics. According to results, it has appeared as the impact of factors “process management”, qualifications of the facility employees”, “qualifications of the facility”, “repurchase and recommend behaviors” on satisfaction of the consumer and these factors vary according totheir demographic characteristics.

  16. Small ncRNA Expression-Profiling of Blood from Hemophilia A Patients Identifies miR-1246 as a Potential Regulator of Factor 8 Gene.

    Directory of Open Access Journals (Sweden)

    Tewarit Sarachana

    Full Text Available Hemophilia A (HA is a bleeding disorder caused by deficiency of functional plasma clotting factor VIII (FVIII. Genetic mutations in the gene encoding FVIII (F8 have been extensively studied. Over a thousand different mutations have been reported in the F8 gene. These span a diverse range of mutation types, namely, missense, splice-site, deletions of single and multiple exons, inversions, etc. There is nonetheless evidence that other molecular mechanisms, in addition to mutations in the gene encoding the FVIII protein, may be involved in the pathobiology of HA. In this study, global small ncRNA expression profiling analysis of whole blood from HA patients, and controls, was performed using high-throughput ncRNA microarrays. Patients were further sub-divided into those that developed neutralizing-anti-FVIII antibodies (inhibitors and those that did not. Selected differentially expressed ncRNAs were validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR analysis. We identified several ncRNAs, and among them hsa-miR-1246 was significantly up-regulated in HA patients. In addition, miR-1246 showed a six-fold higher expression in HA patients without inhibitors. We have identified an miR-1246 target site in the noncoding region of F8 mRNA and were able to confirm the suppressory role of hsa-miR-1246 on F8 expression in a stable lymphoblastoid cell line expressing FVIII. These findings suggest several testable hypotheses vis-à-vis the role of nc-RNAs in the regulation of F8 expression. These hypotheses have not been exhaustively tested in this study as they require carefully curated clinical samples.

  17. MiR-34a inhibits colon cancer proliferation and metastasis by inhibiting platelet-derived growth factor receptor α.

    Science.gov (United States)

    Li, Chunyan; Wang, Yulin; Lu, Shuming; Zhang, Zhuqing; Meng, Hua; Liang, Lina; Zhang, Yan; Song, Bo

    2015-11-01

    The microRNA (miRNA), miR‑34a is significant in colon cancer progression. In the present study, the role of miR‑34a in colon cancer cell proliferation and metastasis was investigated. It was found that the expression of miR‑34a in colon cancer tissues and cell lines was lower when compared with that of normal tissues and cells. Further research demonstrated that miR‑34a inhibited cell proliferation, induced G1 phase arrest, and suppressed metastasis and epithelial mesenchymal transition in colon cancer cells. Bioinformatic prediction indicated that platelet‑derived growth factor receptor α (PDGFRA) was a potential target gene of miR‑34a and a luciferase assay identified that PDGFRA was a novel direct target gene of miR‑34a. In addition, assays of western blot analyses and quantitative reverse‑transcription polymerase chain reaction confirmed that miR‑34a decreased PDGFRA mRNA expression and protein levels in colon cancer cells. Assessment of cellular function indicated that miR‑34a inhibited colon cancer progression via PDGFRA. These findings demonstrate that miR‑34a may act as a negative regulator in colon cancer by targeting PDGFRA.

  18. Combinatorial analysis of lupulin gland transcription factors from R2R3Myb, bHLH and WDR families indicates a complex regulation of chs_H1 genes essential for prenylflavonoid biosynthesis in hop (Humulus Lupulus L.

    Directory of Open Access Journals (Sweden)

    Matoušek Jaroslav

    2012-02-01

    Full Text Available Abstract Background Lupulin glands of hop produce a specific metabolome including hop bitter acids valuable for the brewing process and prenylflavonoids with promising health-beneficial activities. The detailed analysis of the transcription factor (TF-mediated regulation of the oligofamily of one of the key enzymes, i.e., chalcone synthase CHS_H1 that efficiently catalyzes the production of naringenin chalcone, a direct precursor of prenylflavonoids in hop, constitutes an important part of the dissection of the biosynthetic pathways leading to the accumulation of these compounds. Results Homologues of flavonoid-regulating TFs HlMyb2 (M2, HlbHLH2 (B2 and HlWDR1 (W1 from hop were cloned using a lupulin gland-specific cDNA library from the hop variety Osvald's 72. Using a "combinatorial" transient GUS expression system it was shown that these unique lupulin-gland-associated TFs significantly activated the promoter (P of chs_H1 in ternary combinations of B2, W1 and either M2 or the previously characterized HlMyb3 (M3. The promoter activation was strongly dependent on the Myb-P binding box TCCTACC having a core sequence CCWACC positioned on its 5' end region and it seems that the complexity of the promoter plays an important role. M2B2W1-mediated activation significantly exceeded the strength of expression of native chs_H1 gene driven by the 35S promoter of CaMV, while M3B2W1 resulted in 30% of the 35S:chs_H1 expression level, as quantified by real-time PCR. Another newly cloned hop TF, HlMyb7, containing a transcriptional repressor-like motif pdLNLD/ELxiG/S (PDLNLELRIS, was identified as an efficient inhibitor of chs_H1-activating TFs. Comparative analyses of hop and A. thaliana TFs revealed a complex activation of Pchs_H1 and Pchs4 in combinatorial or independent manners. Conclusions This study on the sequences and functions of various lupulin gland-specific transcription factors provides insight into the complex character of the regulation of the

  19. The RosR transcription factor is required for gene expression dynamics in response to extreme oxidative stress in a hypersaline-adapted archaeon

    Directory of Open Access Journals (Sweden)

    Sharma Kriti

    2012-07-01

    Full Text Available Abstract Background Previous work has shown that the hypersaline-adapted archaeon, Halobacterium salinarum NRC-1, is highly resistant to oxidative stress caused by exposure to hydrogen peroxide, UV, and gamma radiation. Dynamic alteration of the gene regulatory network (GRN has been implicated in such resistance. However, the molecular functions of transcription regulatory proteins involved in this response remain unknown. Results Here we have reanalyzed several existing GRN and systems biology datasets for H. salinarum to identify and characterize a novel winged helix-turn-helix transcription factor, VNG0258H, as a regulator required for reactive oxygen species resistance in this organism. This protein appears to be unique to the haloarchaea at the primary sequence level. High throughput quantitative growth assays in a deletion mutant strain implicate VNG0258H in extreme oxidative stress resistance. According to time course gene expression analyses, this transcription factor is required for the appropriate dynamic response of nearly 300 genes to reactive oxygen species damage from paraquat and hydrogen peroxide. These genes are predicted to function in repair of oxidative damage to proteins and DNA. In vivo DNA binding assays demonstrate that VNG0258H binds DNA to mediate gene regulation. Conclusions Together these results suggest that VNG0258H is a novel archaeal transcription factor that regulates gene expression to enable adaptation to the extremely oxidative, hypersaline niche of H. salinarum. We have therefore renamed VNG0258H as RosR, for reactive oxygen species regulator.

  20. Cloning and expression of feline colony stimulating factor receptor (CSF-1R) and analysis of the species specificity of stimulation by colony stimulating factor-1 (CSF-1) and interleukin-34 (IL-34)

    Science.gov (United States)

    Gow, Deborah J.; Garceau, Valerie; Pridans, Clare; Gow, Adam G.; Simpson, Kerry E.; Gunn-Moore, Danielle; Hume, David A.

    2013-01-01

    Colony stimulating factor (CSF-1) and its receptor, CSF-1R, have been previously well studied in humans and rodents to dissect the role they play in development of cells of the mononuclear phagocyte system. A second ligand for the CSF-1R, IL-34 has been described in several species. In this study, we have cloned and expressed the feline CSF-1R and examined the responsiveness to CSF-1 and IL-34 from a range of species. The results indicate that pig and human CSF-1 and human IL-34 are equally effective in cats, where both mouse CSF-1 and IL-34 are significantly less active. Recombinant human CSF-1 can be used to generate populations of feline bone marrow and monocyte derived macrophages that can be used to further dissect macrophage-specific gene expression in this species, and to compare it to data derived from mouse, human and pig. These results set the scene for therapeutic use of CSF-1 and IL-34 in cats. PMID:23260168

  1. Expression of CD40 is a positive prognostic factor of diffuse large B-cell lymphoma treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone

    Directory of Open Access Journals (Sweden)

    Song G

    2016-06-01

    Full Text Available Guoqi Song,1 Huiyun Ni,1 Linqing Zou,2 Shukui Wang,3 Fuliang Tian,4 Hong Liu,1 William C Cho5 1Department of Hematology, Affiliated Hospital of Nantong University, Nantong, 2Department of Human Anatomy, Nantong University, Nantong, 3Central Laboratory of Nanjing First Hospital, Nanjing Medical University, Nanjing, 4Maternal and Child Health Hospital of Lianyungang, Lianyungang, Jiangsu, People’s Republic of China; 5Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong Objectives: The objective of this study was to investigate the expression level of CD40 and its role in the prognosis of patients with diffuse large B-cell lymphoma (DLBCL who were treated with rituximab-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.Design and methods: The immunohistochemical expressions of CD40 in 186 well-characterized DLBCL patients were evaluated by tissue microarrays, thereby revealing the relationship of the molecule CD40 with known tumor, patient-related variables, and survival rates.Results: The results showed that CD40 expressions were not statistically different between the germinal center B-cell-like (GCB type and the non-GCB type. We also analyzed the relationships of CD40 expression with overall survival (OS and progression-free survival (PFS in DLBCL patients who were uniformly treated with R-CHOP. A low expression of CD40 compared to high expression is related to poor OS and PFS. Conclusion: Our findings indicate that the CD40 level at onset acts as an independent prognostic predictor of DLBCL patients treated with R-CHOP. Keywords: CD40, diffuse large B-cell lymphoma, R-CHOP, prognostic factor

  2. Pharmacokinetics, biodistribution and dosimetry of 99mTc-labeled anti-human epidermal growth factor receptor humanized monoclonal antibody R3 in rats.

    Science.gov (United States)

    Iznaga Escobar, N; Morales, A M; Ducongé, J; Torres, I C; Fernández, E; Gómez, J A

    1998-01-01

    The pharmacokinetics, biodistribution and dosimetry of 99mTc-labeled anti-human epidermal growth factor receptor (anti-hEGF-r) humanized monoclonal antibody (MAb) R3 was investigated following intravenous injection in normal Wistar rats. Serum disappearance curves were best fit by a two-compartment model having a mean distribution half-life (t 1/2alpha) of 0.250 h and a mean elimination (t 1/2beta) of 13.89 h. Among the various organs, a little accumulation of the radiolabeled antibody was found only in kidneys. Biodistribution and dosimetry studies in humans were performed by extrapolation of the animal data to humans. Absorbed dose to normal organs and the remainder of the whole body were estimated using the medical internal radiation dose formula, and dose contributions from radioactivity in transit through the gastrointestinal tract were estimated using a compartment model. Extrapolated values of radiation absorbed dose to normal organs in rads per millicurie administered were whole body, 0.0085; lower large intestine wall, 0.0898; small intestine, 0.0530; upper large intestine wall, 0.0731; and kidneys, 0.0455. The effective dose equivalent predicted was 0.0162 rem/mCi and the effective dose was found to be 0.015 rem/mCi. On the basis of the pharmacokinetics, biodistribution and internal radiation dosimetry information obtained in this study, a diagnostic phase I clinical trial with 99mTc-labeled humanized MAb R3 conjugate in patients should be supported.

  3. Enhanced neuroprotection and improved motor function in traumatized rat spinal cords by rAAV2-mediated Glial-derived neurotrophic factor combined with early rehabilitation training

    Institute of Scientific and Technical Information of China (English)

    Han Qingquan; Xiang Jingjing; Zhang Yun; Qiao Hujun; Shen Yongwei; Zhang Chun

    2014-01-01

    Background Spinal cord injury (SCI) is a serious neurological injury that often leads to permanent disabilities for the victims.The aim of this study was to determine the effects of glial-derived neurotrophic factor (GDNF) mediated by recombinant adeno-associated virus type 2 (rAAV2) alone or in combination with early rehabilitation training on SCI.Methods SCI was induced on the T8-9 segments of the spinal cord by laminectomy in adult male Sprague-Dawley rats.Then besides the sham operation group,the SCI rats were randomly divided into four groups:natural healing group,gene therapy group,rehabilitation training group,and combination therapy group (gene therapy in combination with rehabilitation training).Motor dysfunction,protein expression of GDNF,edema formation,and cell injury were examined 7,14,and 21 days after trauma.Results The topical application of rAAV-GDNF-GFP resulted in strong expression of GDNF,especially after the 14th day,and could protect the motor neuron ceils.Early rehabilitative treatment resulted in significantly improved motor function,reduced edema formation,and protected the cells from injury,especially after the 7th and 14th days,and increased the GDNF expression in the damaged area,which was most evident after Day 14.The combined application of GDNF and early rehabilitative treatment after SCI resulted in a significant reduction in spinal cord pathology and motor dysfunction after the 7th and 14th days.Conclusion These observations suggest that rAAV2 gene therapy in combination with rehabilitation therapy has potential clinical value for the treatment of SCI.

  4. Effects of single-base substitutions within the acanthamoeba castellanii rRNA promoter on transcription and on binding of transcription initiation factor and RNA polymerase I

    Energy Technology Data Exchange (ETDEWEB)

    Kownin, P.; Bateman, E.; Paule, M.R.

    1988-02-01

    Single-point mutations were introduced into the promoter region of the Acanthamoeba castellanii rRNA gene by chemical mutagen treatment of a single-stranded clone in vitro, followed by reverse transcription and cloning of the altered fragment. The promoter mutants were tested for transcription initiation factor (TIF) binding by a template commitment assay plus DNase I footprinting and for transcription by an in vitro runoff assay. Point mutations within the previously identified TIF interaction region (between -20 and -47, motifs A and B) indicated that TIF interacts most strongly with a sequence centered at -29 and less tightly with sequences upstream and downstream. Some alterations of the base sequence closer to the transcription start site (and outside the TIF-protected site) also significantly decrease specific RNA synthesis in vitro. These were within the region which is protected from DNAse I digestion by polymerase I, but these mutations did not detectably affect the binding of polymerase to the promoter.

  5. Functional high-throughput screening identifies the miR-15 microRNA family as cellular restriction factors for Salmonella infection.

    Science.gov (United States)

    Maudet, Claire; Mano, Miguel; Sunkavalli, Ushasree; Sharan, Malvika; Giacca, Mauro; Förstner, Konrad U; Eulalio, Ana

    2014-08-22

    Increasing evidence suggests an important role for miRNAs in the molecular interplay between bacterial pathogens and host cells. Here we perform a fluorescence microscopy-based screen using a library of miRNA mimics and demonstrate that miRNAs modulate Salmonella infection. Several members of the miR-15 miRNA family were among the 17 miRNAs that more efficiently inhibit Salmonella infection. We discovered that these miRNAs are downregulated during Salmonella infection, through the inhibition of the transcription factor E2F1. Analysis of miR-15 family targets revealed that derepression of cyclin D1 and the consequent promotion of G1/S transition are crucial for Salmonella intracellular proliferation. In addition, Salmonella induces G2/M cell cycle arrest in infected cells, further promoting its replication. Overall, these findings uncover a mechanism whereby Salmonella renders host cells more susceptible to infection by controlling cell cycle progression through the active modulation of host cell miRNAs.

  6. MiR-577 inhibits pancreatic β-cell function and survival by targeting fibroblast growth factor 21 (FGF-21) in pediatric diabetes.

    Science.gov (United States)

    Chen, X Y; Li, G M; Dong, Q; Peng, H

    2015-12-01

    Pancreatic β-cell dysfunction is a central component of the pathogenesis of pediatric diabetes. MicroRNA (miRNA) have become one of the most encouraging and fruitful fields in biological research, and have been implicated as new players in the pathogenesis of diabetes and diabetes-associated complications. The role of miRNA in diabetes begins with the development of pancreatic islets. Fibroblast growth factor (FGF)-21 enhances glucose uptake in adipocytes, protecting transgenic animals from diet-induced obesity when overexpressed, and lowers blood glucose and triglyceride levels in diabetic animals (when administered); therefore, it is a good way to treat diabetes. However, the mechanism of miRNA in regulation of FGF21 is not known. In this study, FGF-21 was predicted to be the target of miR-577. Therefore, we investigated the effects of miR-577 on β-cell function and survival by targeting FGF-21. We demonstrated that, although FGF-21 does not acutely stimulate insulin secretion in isolated islets from normal rats, it increases insulin secretion and insulin content in diabetic islets and protects β-cells from apoptosis via the activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways.

  7. Intermittent hypoxia with or without hypercapnia is associated with tumorigenesis by decreasing the expression of brain derived neurotrophic factor and miR-34a in rats

    Institute of Scientific and Technical Information of China (English)

    Zhang Jing; Guo Xu; Shi Yanwei; Ma Jing; Wang Guangfa

    2014-01-01

    Background Very recent studies revealed that obstructive sleep apnoea (OSA) is a contributor of the increased incidence and mortality of cancer in humans,but mechanisms of how OSA promotes tumorigenesis remains largely unknown.We investigated whether intermittent hypoxia with and without hypercapnia plays a role in tumorigenesis.Methods First,Sprague-Dawley (SD) male rats (12 weeks old) were subjected to different hypoxia exposures:intermittent hypoxia and intermittent hypoxia with hypercapnia; continuous hypoxia and normal air.The systemic application of chronic fast rate hypoxia with or without hypercapnia mimicked severe OSA patients with apnoea/hypopnea index equivalent to 60 events per hour.Then routine blood tests were performed and the levels of brain derived neurotrophic factor (BDNF) and miR-34a were examined.Results In contrast to intermittent hypoxia with hypercapnia,both intermittent hypoxia and continuous hypoxia treatments caused significantly higher levels of haematology parameters than normoxia treatments.Compared to normoxia,intermittent hypoxia with hypercapnia exposure resulted in substantial decrease of serum BDNF and,miR-34a in the lower brainstem,while less pronounced results were found in intermittent hypoxia and continuous hypoxia exposure.Conclusions The exposure of intermittent hypoxia with or without hypercapnia,mimicking the situations in severe OSA patients,was associated with,or even promoted tumorigenesis.

  8. Slope stability, triggering factors and threshold conditions. Study of debris flow activity in the Reyðarfjörður fjord, eastern Iceland.

    Science.gov (United States)

    Margeirsson, Guðbjörn; Sæmundsson, Þorsteinn; Norðdahl, Hreggviður

    2016-04-01

    Precipitation is one of the main triggering factor for debris flow activity in Eastern Iceland, but the amount needed, duration and the rainfall and its intensity to trigger the flow (e.g. the threshold condition) can vary considerably between areas. There are a few factors that have to be taken into account to determine the threshold condition and slope stability between areas, such as the slope angle and aspect, type and thickness of loose material, vegetation cover and gully distribution. Weather factors such as air and soil temperature, wind speed and wind direction is also crucial. The study area is located in the Reyðarfjörður fjord, one of the longest fjords on the east coast of Iceland. It is a 30 km long glacially eroded fjord, cut into the Tertiary bedrock. The bedrock is mostly made up of jointed basaltic lava flows, individual flows can vary in thickness from 2-30 m and usually separated by lithified sedimentary horizons often red in color. The slopes of the fjord are steep up to 900 m high, often consisting of nearly vertical cliffs, 60°-90°, in the upper parts of the slopes. The lower parts are covered with various glaciogenic landforms and consist of sediments and talus material. Several small hanging valleys and numerous small gullies and streams occur along the both sides of the fjord. The debris flow activity in the Reyðafjörður fjord is mostly constrained to the gullies and streams. Some activity has also been observed on the slopes between the gullies, but such activity is usually connected to extreme conditions, during or following heavy rain storms or a rainfall, especially of long duration. The aim of the study is to map the distribution of loose slope sediments in two areas inside the fjord, collect data about the known debris flow history, analyze various weather patterns which have contributed to these debris flows and understand how variables between the slopes react differently to different factors.

  9. RESPONSE MODIFICATION FACTOR R AND OVERSTRENGTH FACTOR OF Y-ECCENTRIC BRACED STEEL FRAME%Y形偏心支撑钢框架的地震反应折减系数和超强系数

    Institute of Scientific and Technical Information of China (English)

    杨文侠; 顾强; 宋振森; 李东; 方有珍

    2012-01-01

    该文采用静力推覆和能力谱方法分析了基于我国抗震规范设计的12个Y形偏心支撑钢框架的地震反应折减系数R和超强系数及赘余度超强系数3,分析了结构层数、楼层高跨比对各系数的影响。研究结果表明:Y形偏心支撑钢框架的设计地震作用可在我国现行抗震规范的基础上降低20%左右。%Twelve Y-eccentric braced steel frames were designed to complie with Chinese seismic code. The response modification factor R, overstrength factor and redundancy factor of each building were evaluated by the capacity spectrum method combined with the global capacity envelops obtained from an improved pushover analysis. Moreover, the effects of storey numbers and spans of the structure on these factors were analyzed. The results show that the 20% elastic design earthquake action of Y-eccentric braced steel frames can be approximately reduced on the base of Chinese seismic code.

  10. Differences in problem behaviour among ethnic minority and majority preschoolers in the Netherlands and the role of family functioning and parenting factors as mediators: the Generation R Study

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    Flink Ilse JE

    2012-12-01

    Full Text Available Abstract Background Studies have shown that, compared to native counterparts, preschoolers from ethnic minorities are at an increased risk of problem behaviour. Socio-economic factors only partly explain this increased risk. This study aimed to further unravel the differences in problem behaviour among ethnic minority and native preschoolers by examining the mediating role of family functioning and parenting factors. Methods We included 4,282 preschoolers participating in the Generation R Study, an ethnically-diverse cohort study with inclusion in early pregnancy. At child age 3 years, parents completed the Child Behavior Checklist (CBCL/1,5-5; information on demographics, socio-economic status and measures of family functioning (maternal psychopathology; general family functioning and parenting (parenting stress; harsh parenting were retrieved from questionnaires. CBCL Total Problems scores in each ethnic subgroup were compared with scores in the Dutch reference population. Mediation was evaluated using multivariate regression models. Results After adjustment for confounders, preschoolers from ethnic minorities were more likely to present problem behaviour than the Dutch subgroup (e.g. CBCL Total Problems Turkish subgroup (OR 7.0 (95% CI 4.9; 10.1. When considering generational status, children of first generation immigrants were worse off than the second generation (P Conclusions This study showed that preschoolers from ethnic minorities and particularly children of first generation immigrants are at an increased risk of problem behaviour compared to children born to a Dutch mother. Although socio-economic factors were found to partly explain the association between the ethnic minority status and child problem behaviour, a similar part was explained by family functioning and parenting factors. Considering these findings, it is important for health care workers to also be attentive to symptoms of parental psychopathology (e.g. depression, poor

  11. HRP-2, the Caenorhabditis elegans homolog of mammalian heterogeneous nuclear ribonucleoproteins Q and R, is an alternative splicing factor that binds to UCUAUC splicing regulatory elements.

    Science.gov (United States)

    Kabat, Jennifer L; Barberan-Soler, Sergio; Zahler, Alan M

    2009-10-16

    Alternative splicing is regulated by cis sequences in the pre-mRNA that serve as binding sites for trans-acting alternative splicing factors. In a previous study, we used bioinformatics and molecular biology to identify and confirm that the intronic hexamer sequence UCUAUC is a nematode alternative splicing regulatory element. In this study, we used RNA affinity chromatography to identify trans factors that bind to this sequence. HRP-2, the Caenorhabditis elegans homolog of human heterogeneous nuclear ribonucleoproteins Q and R, binds to UCUAUC in the context of unc-52 intronic regulatory sequences as well as to RNAs containing tandem repeats of this sequence. The three Us in the hexamer are the most important determinants of this binding specificity. We demonstrate, using RNA interference, that HRP-2 regulates the alternative splicing of two genes, unc-52 and lin-10, both of which have cassette exons flanked by an intronic UCUAUC motif. We propose that HRP-2 is a protein responsible for regulating alternative splicing through binding interactions with the UCUAUC sequence.

  12. A common polymorphism in the brain-derived neurotrophic factor gene (BDNF) modulates human cortical plasticity and the response to rTMS.

    Science.gov (United States)

    Cheeran, Binith; Talelli, Penelope; Mori, Francesco; Koch, Giacomo; Suppa, Antonio; Edwards, Mark; Houlden, Henry; Bhatia, Kailash; Greenwood, Richard; Rothwell, John C

    2008-12-01

    The brain-derived neurotrophic factor gene (BDNF) is one of many genes thought to influence synaptic plasticity in the adult brain and shows a common single nucleotide polymorphism (BDNF Val66Met) in the normal population that is associated with differences in hippocampal volume and episodic memory. It is also thought to influence possible synaptic changes in motor cortex following a simple motor learning task. Here we extend these studies by using new non-invasive transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (TDCS) techniques that directly test the excitability and plasticity of neuronal circuits in human motor cortex in subjects at rest. We investigated whether the susceptibility to TMS probes of plasticity is significantly influenced by the BDNF polymorphism. Val66Met carriers were matched with Val66Val individuals and tested on the following protocols: continuous and intermittent theta burst TMS; median nerve paired associative stimulation; and homeostatic plasticity in the TDCS/1 Hz rTMS model. The response of Met allele carriers differed significantly in all protocols compared with the response of Val66Val individuals. We suggest that this is due to the effect of BNDF on the susceptibility of synapses to undergo LTP/LTD. The circuits tested here are implicated in the pathophysiology of movement disorders such as dystonia and are being assessed as potential new targets in the treatment of stroke. Thus the polymorphism may be one factor that influences the natural response of the brain to injury and disease.

  13. Predictive factors of ovarian response and clinical outcome after IVF/ICSI following a rFSH/GnRH antagonist protocol with or without oral contraceptive pre-treatment

    DEFF Research Database (Denmark)

    Andersen, A Nyboe; Witjes, H; Gordon, K

    2011-01-01

    Prediction of ovarian response prior to the first controlled ovarian stimulation (COS) cycle is useful in determining the optimal starting dose of recombinant FSH (rFSH). However, potentially predictive factors may be subject to inter-cycle variability and many patients are pre-treated with oral...... contraceptives (OC) for scheduling purposes. Our objective was to determine predictive factors of ovarian response for patients undergoing COS with rFSH in a gonadotrophin-releasing hormone antagonist protocol and to determine the inter-cycle variability of these factors....

  14. Predictive factors of ovarian response and clinical outcome after IVF/ICSI following a rFSH/GnRH antagonist protocol with or without oral contraceptive pre-treatment

    DEFF Research Database (Denmark)

    Andersen, A Nyboe; Witjes, H; Gordon, K

    2011-01-01

    Prediction of ovarian response prior to the first controlled ovarian stimulation (COS) cycle is useful in determining the optimal starting dose of recombinant FSH (rFSH). However, potentially predictive factors may be subject to inter-cycle variability and many patients are pre-treated with oral ...... contraceptives (OC) for scheduling purposes. Our objective was to determine predictive factors of ovarian response for patients undergoing COS with rFSH in a gonadotrophin-releasing hormone antagonist protocol and to determine the inter-cycle variability of these factors....

  15. Assessing gene-environment interaction effects of FTO, MC4R and lifestyle factors on obesity using an extreme phenotype sampling design: Results from the HUNT study.

    Science.gov (United States)

    Bjørnland, Thea; Langaas, Mette; Grill, Valdemar; Mostad, Ingrid Løvold

    2017-01-01

    Our aim was to assess the influence of age, gender and lifestyle factors on the effect of the obesity-promoting alleles of FTO and MCR4. The HUNT study comprises health information on the population of Nord-Trøndelag county, Norway. Extreme phenotype participants (gender-wise lower and upper quartiles of waist-hip-ratio and BMI ≥ 35 kg/m2) in the third survey, HUNT3 (2006-08), were genotyped for the single-nucleotide polymorphisms rs9939609 (FTO) and rs17782313 (MC4R); 25686 participants were successfully genotyped. Extreme sampling was chosen to increase power to detect genetic and gene-environment effects on waist-hip-ratio and BMI. Statistical inference was based on linear regression models and a missing-covariate likelihood approach for the extreme phenotype sampling design. Environmental factors were physical activity, diet (artificially sweetened beverages) and smoking. Longitudinal analysis was performed using material from HUNT2 (1995-97). Cross-sectional and longitudinal genetic effects indicated stronger genetic associations with obesity in young than in old, as well as differences between women and men. We observed larger genetic effects among physically inactive compared to active individuals. This interaction was age-dependent and seen mainly in 20-40 year olds. We observed a greater FTO effect among men with a regular intake of artificially sweetened beverages, compared to non-drinkers. Interaction analysis of smoking was mainly inconclusive. In a large all-adult and area-based population survey the effects of obesity-promoting minor-alleles of FTO and MCR4, and interactions with life style factors are age- and gender-related. These findings appear relevant when designing individualized treatment for and prophylaxis against obesity.

  16. Recombinant Activated Factor VIIa (rFVIIa) Treatment in Very-Low-Birth-Weight (VLBW) Premature Infants with Acute Pulmonary Hemorrhage: A Single-Center, Retrospective Study.

    Science.gov (United States)

    Cosar, Hese; Isik, Halil; Cakır, Salih Cagrı; Yar, Nese; Goksen, Bulent; Tokbay, Hakan; Kertmen, Hasan; Erdoğan, Nihal; Durak, Ikbal

    2017-02-01

    We aimed to evaluate the efficacy of intravenous administration of recombinant activated factor VIIa (rFVIIa) for acute pulmonary hemorrhage treatment in very-low-birth-weight (VLBW) premature infants. This study was carried out retrospectively in premature infants with pulmonary hemorrhage that were ≤30 weeks gestational age or premature infants with pulmonary hemorrhage who were hospitalized in our neonatal intensive care unit between 01 January 2013 and 31 December 2015 were evaluated. Group 1 (n = 21) received rFVIIa support within the first 30 min of pulmonary hemorrhage plus conventional treatment, while Group 2 (n = 21) received conventional treatment only. The number of patients whose pulmonary hemorrhage was stopped within the first 2 h was significantly higher in Group 1 than Group 2 (n = 14 vs n = 4; p = 0.002). After pulmonary hemorrhage, hemoglobin values of Group 1 were higher than Group 2 (11.12 ± 1.06 vs 10.14 ± 1.59 g/dL; p = 0.024). Erythrocyte suspension (1.43 ± 4.51 vs 5.71 ± 7.46 mL/kg; p = 0.030) and fresh frozen plasma use (5.71 ± 8.10 vs 19.52 ± 12.44 mL/kg; p premature infants.

  17. Predicting Persistent Back Symptoms by Psychosocial Risk Factors: Validity Criteria for the OMPSQ and the HKF-R 10 in Germany.

    Directory of Open Access Journals (Sweden)

    E Riewe

    Full Text Available 10% of all individuals in Germany develop persistent symptoms due to nonspecific back pain (NSBP causing up to 90% of direct and indirect expenses for health care systems. Evidence indicates a strong relationship between chronic nonspecific back pain and psychosocial risk factors. The Örebro Musculoskeletal Pain Screening Questionnaire (ÖMPSQ and the German Heidelberger Kurzfragebogen Rückenschmerz (HKF-R 10 are deemed valid in prediction of persistent pain, functional loss or amount of sick leave. This study provides and discusses validity criteria for these questionnaires using ROC-curve analyses. Quality measurements included sensitivity and specificity, likelihood-ratio related test-efficiencies and clinical utility in regard to predictive values.265 patients recruited from primary and secondary care units completed both questionnaires during the same timeframe. From the total, 133 patients returned a 6-month follow-up questionnaire to assess the validity criteria for outcomes of pain, function and sick leave.Based on heterogeneous cut-offs for the ÖMPSQ, sensitivity and specificity were moderate for outcome of pain (72%/75%. Very high sensitivity was observed for function (97%/57% and high specificity for sick leave (63%/85%. The latter also applied to the HKF-R 10 (pain 50%/84%. Proportions between sensitivity and specificity were unbalanced except for the ÖMPSQ outcome of pain. Likelihood-ratios and positive predictive values ranged from low to moderate.Although the ÖMPSQ may be considered useful in identification of long-term functional loss or pain, over- and underestimation of patients at risk of chronic noncspecific back pain led to limited test-efficiencies and clinical utility for both questionnaires. Further studies are required to quantify the predictive validity of both questionnaires in Germany.

  18. Transcription factor CecR (YbiH) regulates a set of genes affecting the sensitivity of Escherichia coli against cefoperazone and chloramphenicol.

    Science.gov (United States)

    Yamanaka, Yuki; Shimada, Tomohiro; Yamamoto, Kaneyoshi; Ishihama, Akira

    2016-07-01

    Genomic SELEX (systematic evolution of ligands by exponential enrichment) screening was performed for identification of the binding site of YbiH, an as yet uncharacterized TetR-family transcription factor, on the Escherichia coli genome. YbiH was found to be a unique single-target regulator that binds in vitro within the intergenic spacer located between the divergently transcribed ybiH-ybhGFSR and rhlE operons. YbhG is an inner membrane protein and YbhFSR forms a membrane-associated ATP-binding cassette (ABC) transporter while RhlE is a ribosome-associated RNA helicase. Gel shift assay and DNase footprinting analyses indicated one clear binding site of YbiH, including a complete palindromic sequence of AATTAGTT-AACTAATT. An in vivo reporter assay indicated repression of the ybiH operon and activation of the rhlE operon by YbiH. After phenotype microarray screening, YbiH was indicated to confer resistance to chloramphenicol and cefazoline (a first-generation cephalosporin). A systematic survey of the participation of each of the predicted YbiH-regulated genes in the antibiotic sensitivity indicated involvement of the YbhFSR ABC-type transporter in the sensitivity to cefoperazone (a third-generation cephalosporin) and of the membrane protein YbhG in the control of sensitivity to chloramphenicol. Taken together with the growth test in the presence of these two antibiotics and in vitro transcription assay, it was concluded that the hitherto uncharacterized YbiH regulates transcription of both the bidirectional transcription units, the ybiH-ybhGFSR operon and the rhlE gene, which altogether are involved in the control of sensitivity to cefoperazone and chloramphenicol. We thus propose to rename YbiH as CecR (regulator of cefoperazone and chloramphenicol sensitivity).

  19. Fox-2 Splicing Factor Binds to a Conserved Intron Motif to PromoteInclusion of Protein 4.1R Alternative Exon 16

    Energy Technology Data Exchange (ETDEWEB)

    Ponthier, Julie L.; Schluepen, Christina; Chen, Weiguo; Lersch,Robert A.; Gee, Sherry L.; Hou, Victor C.; Lo, Annie J.; Short, Sarah A.; Chasis, Joel A.; Winkelmann, John C.; Conboy, John G.

    2006-03-01

    Activation of protein 4.1R exon 16 (E16) inclusion during erythropoiesis represents a physiologically important splicing switch that increases 4.1R affinity for spectrin and actin. Previous studies showed that negative regulation of E16 splicing is mediated by the binding of hnRNP A/B proteins to silencer elements in the exon and that downregulation of hnRNP A/B proteins in erythroblasts leads to activation of E16 inclusion. This paper demonstrates that positive regulation of E16 splicing can be mediated by Fox-2 or Fox-1, two closely related splicing factors that possess identical RNA recognition motifs. SELEX experiments with human Fox-1 revealed highly selective binding to the hexamer UGCAUG. Both Fox-1 and Fox-2 were able to bind the conserved UGCAUG elements in the proximal intron downstream of E16, and both could activate E16 splicing in HeLa cell co-transfection assays in a UGCAUG-dependent manner. Conversely, knockdown of Fox-2 expression, achieved with two different siRNA sequences resulted in decreased E16 splicing. Moreover, immunoblot experiments demonstrate mouse erythroblasts express Fox-2, but not Fox-1. These findings suggest that Fox-2 is a physiological activator of E16 splicing in differentiating erythroid cells in vivo. Recent experiments show that UGCAUG is present in the proximal intron sequence of many tissue-specific alternative exons, and we propose that the Fox family of splicing enhancers plays an important role in alternative splicing switches during differentiation in metazoan organisms.

  20. The impact of the stromal cell-derived factor-1-3'A and E-selectin S128R polymorphisms on breast cancer.

    Science.gov (United States)

    Kontogianni, Panagiota; Zambirinis, Constantinos P; Theodoropoulos, George; Gazouli, Maria; Michalopoulos, Nikolaos V; Flessas, John; Liberi, Maria; Zografos, George C

    2013-01-01

    Breast cancer is prone to metastasis even in early stage disease. Stromal cell-derived factor-1 (SDF-1) is a chemokine that has been associated with the egress of cancer cells from the primary focus and homing to distant sites, while E-selectin has been implicated in their trans-endothelial migration. This study was performed to evaluate the association between SDF-1-3'A and E-selectin S128R-two polymorphisms associated with enhanced function-and the risk of breast cancer, as well as their influence on breast cancer outcome. A retrospective analysis was conducted on 261 patients and 480 healthy controls using PCR-RFLP. The frequencies for the wild-type (GG), GA and AA genotypes of SDF-1 were 43.7, 45.2, and 11.1 % in patients, and 51.5, 41.3, and 7.3 % in healthy controls, respectively, while the SDF-1-3'A allelic frequency was 33.7 % at patients and 27.9 % at controls. The SDF-1-3'A carrier group of patients and the A allele of SDF-1 were overrepresented among the breast cancer cases (p = 0.04 and 0.02, respectively). For the E-selectin S128R polymorphism, the frequencies for the wild-type (AA), AC and CC genotypes were 58.6, 38.3, and 3.1 % in patients and 63.8, 31.4, and 3.8 % in controls, respectively, while the C allelic frequency was 22.2 % for patients and 19.5 % for controls. The CC genotype was associated with poorer survival. Otherwise, no significant association was detected between examined genotypes and tumor characteristics. Overall, our findings support that the SDF-1-3'A confers increased susceptibility to breast cancer and that the E-selectin S128R CC genotype may be related to poorer prognosis. Investigation in bigger cohorts of patients is warranted.

  1. Protective role of R-spondin1, an intestinal stem cell growth factor, against radiation-induced gastrointestinal syndrome in mice.

    Directory of Open Access Journals (Sweden)

    Payel Bhanja

    Full Text Available BACKGROUND: Radiation-induced gastrointestinal syndrome (RIGS results from a combination of direct cytocidal effects on intestinal crypt and endothelial cells and subsequent loss of the mucosal barrier, resulting in electrolyte imbalance, diarrhea, weight loss, infection and mortality. Because R-spondin1 (Rspo1 acts as a mitogenic factor for intestinal stem cells, we hypothesized that systemic administration of Rspo1 would amplify the intestinal crypt cells and accelerate the regeneration of the irradiated intestine, thereby, ameliorating RIGS. METHODS AND FINDINGS: Male C57Bl/6 mice received recombinant adenovirus expressing human R-spondin1 (AdRspo1 or E.coli Lacz (AdLacz, 1-3 days before whole body irradiation (WBI or abdominal irradiation (AIR. Post-irradiation survival was assessed by Kaplan Meier analysis. RIGS was assessed by histological examination of intestine after hematoxilin and eosin staining, immunohistochemical staining of BrdU incorporation, Lgr5 and beta-catenin expression and TUNEL staining. The xylose absorption test (XAT was performed to evaluate the functional integrity of the intestinal mucosal barrier. In order to examine the effect of R-spondin1 on tumor growth, AdRspo1 and AdLacZ was administered in the animals having palpable tumor and then exposed to AIR. There was a significant increase in survival in AdRspo1 cohorts compared to AdLacZ (p<0.003 controls, following WBI (10.4 Gy. Significant delay in tumor growth was observed after AIR in both cohorts AdRspo1 and AdLacZ but AdRspo1 treated animals showed improved survival compared to AdLacZ. Histological analysis and XAT demonstrated significant structural and functional regeneration of the intestine in irradiated animals following AdRspo1 treatment. Immunohistochemical analysis demonstrated an increase in Lgr5+ve crypt cells and the translocation of beta-catenin from the cytosol to nucleus and upregulation of beta-catenin target genes in AdRspo1-treated mice, as

  2. Randomized Phase II Study of Erlotinib in Combination With Placebo or R1507, a Monoclonal Antibody to Insulin-Like Growth Factor-1 Receptor, for Advanced-Stage Non–Small-Cell Lung Cancer

    Science.gov (United States)

    Ramalingam, Suresh S.; Spigel, David R.; Chen, David; Steins, Martin B.; Engelman, Jeffrey A.; Schneider, Claus-Peter; Novello, Silvia; Eberhardt, Wilfried E.E.; Crino, Lucio; Habben, Kai; Liu, Lian; Jänne, Pasi A.; Brownstein, Carrie M.; Reck, Martin

    2011-01-01

    Purpose R1507 is a selective, fully human, recombinant monoclonal antibody (immunoglobulin G1 subclass) against insulin-like growth factor-1 receptor (IGF-1R). The strong preclinical evidence supporting coinhibition of IGF-1R and epidermal growth factor receptor (EGFR) as anticancer therapy prompted this study. Patients and Methods Patients with advanced-stage non–small-cell lung cancer (NSCLC) with progression following one or two prior regimens, Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2, and measurable disease were eligible. Patients were randomly assigned to receive erlotinib (150 mg orally once a day) in combination with either placebo, R1507 9 mg/kg weekly, or R1507 16 mg/kg intravenously once every 3 weeks. Treatment cycles were repeated every 3 weeks. The primary end point was comparison of the 12-week progression-free survival (PFS) rate. Results In all, 172 patients were enrolled: median age, 61 years; female, 33%; never-smokers, 12%; and performance status 0 or 1, 88%. The median number of R1507 doses was six for the weekly arm and 3.5 for the every-3-weeks arm. Grades 3 to 4 adverse events occurred in 37%, 44%, and 48% of patients with placebo, R1507 weekly, and R1507 every 3 weeks, respectively. The 12-week PFS rates were 39%, 37%, and 44%, and the median overall survival was 8.1, 8.1, and 12.1 months for the three groups, respectively, with statistically nonsignificant hazard ratios. The 12-week PFS rate in patients with KRAS mutation was 36% with R1507 compared with 0% with placebo. Conclusion The combination of R1507 with erlotinib did not provide PFS or survival advantage over erlotinib alone in an unselected group of patients with advanced NSCLC. Predictive biomarkers are essential for further development of combined inhibition of IGF-1R and EGFR. PMID:22025157

  3. Construct redundancy within the Five-Factor Model as measured by the NEO PI-R: Implications for emotional intelligence and incremental coherence

    Directory of Open Access Journals (Sweden)

    GILLES E. GIGNAC

    2009-03-01

    Full Text Available Self-report measures of emotional intelligence (EI have been criticized for not being associated with unique validity, independently of comprehensive measures of personality such as the NEO PI-R. In this investigation, the issue of unique validity was re-directed at personality as measured by the facets of the NEO PI-R. Specifically, based on three samples, the personality facet of Depression within the NEO PI-R was found to be so substantially predicted by ten other NEO PI-R facets as to suggest construct redundancy within the NEO PI-R (i.e., R = .93, R = .99, R = .96. Because mixed-models of EI tend to be associated with clearer construct boundaries than personality, it is suggested that EI may be associated with some scientific utility (i.e., ‘incremental coherence’, even in the total absence of any empirically demonstrable unique validity.

  4. Risk factors for otitis media in children with special emphasis on the role of colonization with bacterial airway pathogens: the Generation R study

    Science.gov (United States)

    Labout, Joost A. M.; Duijts, Liesbeth; Lebon, Ankie; de Groot, Ronald; Hofman, Albert; Jaddoe, Vincent V. W.; Verbrugh, Henri A.; Hermans, Peter W. M.

    2010-01-01

    Acute otitis media is the most frequent diagnosis in children visiting physicians’ offices. Risk factors for otitis media have been widely studied. Yet, the correlation between bacterial carriage and the development of otitis media is not entirely clear. Our aim was to study in a population-based prospective cohort the risk factors for otitis media in the second year of life with special emphasis on the role of colonization with Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. The study was embedded in the Generation R Study. Data on risk factors and doctor-diagnosed otitis media were obtained by midwives, hospital registries and postal questionnaires in the whole cohort (n = 7,295). Nasopharyngeal swabs were obtained at the age of 1.5, 6 and 14 months in the focus cohort (n = 1,079). Of these children, 2,515 (47.2%) suffered at least one period of otitis media in their second year of life. The occurrence of otitis media during the follow-up period in the first 6 months of life and between 6 and 12 months of age was associated with the risk of otitis media in the second year of life (aOR, 1.83 95% CI 1.24–2.71 and aOR 2.72, 95% CI 2.18–3.38, respectively). Having siblings was associated with an increased risk for otitis media in the second year of life (aOR 1.42, 95% CI 1.13–1.79). No associations were found between bacterial carriage in the first year of life and otitis media in the second year of life. In our study, otitis media in the first year of life is an independent risk factor for otitis media in the second year of life. Surprisingly, bacterial carriage in the first year of life did not add to this risk. Moreover, no association was observed between bacterial carriage in the first year of life and otitis in the second year of life. PMID:20821039

  5. Risk factors for otitis media in children with special emphasis on the role of colonization with bacterial airway pathogens: the Generation R study.

    Science.gov (United States)

    Labout, Joost A M; Duijts, Liesbeth; Lebon, Ankie; de Groot, Ronald; Hofman, Albert; Jaddoe, Vincent V W; Verbrugh, Henri A; Hermans, Peter W M; Moll, Henriëtte A

    2011-01-01

    Acute otitis media is the most frequent diagnosis in children visiting physicians' offices. Risk factors for otitis media have been widely studied. Yet, the correlation between bacterial carriage and the development of otitis media is not entirely clear. Our aim was to study in a population-based prospective cohort the risk factors for otitis media in the second year of life with special emphasis on the role of colonization with Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. The study was embedded in the Generation R Study. Data on risk factors and doctor-diagnosed otitis media were obtained by midwives, hospital registries and postal questionnaires in the whole cohort (n = 7,295). Nasopharyngeal swabs were obtained at the age of 1.5, 6 and 14 months in the focus cohort (n = 1,079). Of these children, 2,515 (47.2%) suffered at least one period of otitis media in their second year of life. The occurrence of otitis media during the follow-up period in the first 6 months of life and between 6 and 12 months of age was associated with the risk of otitis media in the second year of life (aOR, 1.83 95% CI 1.24-2.71 and aOR 2.72, 95% CI 2.18-3.38, respectively). Having siblings was associated with an increased risk for otitis media in the second year of life (aOR 1.42, 95% CI 1.13-1.79). No associations were found between bacterial carriage in the first year of life and otitis media in the second year of life. In our study, otitis media in the first year of life is an independent risk factor for otitis media in the second year of life. Surprisingly, bacterial carriage in the first year of life did not add to this risk. Moreover, no association was observed between bacterial carriage in the first year of life and otitis in the second year of life.

  6. The influence of Aspergillus niger transcription factors AraR and XlnR in the gene expression during growth in D-xylose, L-arabinose and steam-exploded sugarcane bagasse.

    Science.gov (United States)

    de Souza, Wagner Rodrigo; Maitan-Alfenas, Gabriela Piccolo; de Gouvêa, Paula Fagundes; Brown, Neil Andrew; Savoldi, Marcela; Battaglia, Evy; Goldman, Maria Helena S; de Vries, Ronald P; Goldman, Gustavo Henrique

    2013-11-01

    The interest in the conversion of plant biomass to renewable fuels such as bioethanol has led to an increased investigation into the processes regulating biomass saccharification. The filamentous fungus Aspergillus niger is an important microorganism capable of producing a wide variety of plant biomass degrading enzymes. In A. niger the transcriptional activator XlnR and its close homolog, AraR, controls the main (hemi-)cellulolytic system responsible for plant polysaccharide degradation. Sugarcane is used worldwide as a feedstock for sugar and ethanol production, while the lignocellulosic residual bagasse can be used in different industrial applications, including ethanol production. The use of pentose sugars from hemicelluloses represents an opportunity to further increase production efficiencies. In the present study, we describe a global gene expression analysis of A. niger XlnR- and AraR-deficient mutant strains, grown on a D-xylose/L-arabinose monosaccharide mixture and steam-exploded sugarcane bagasse. Different gene sets of CAZy enzymes and sugar transporters were shown to be individually or dually regulated by XlnR and AraR, with XlnR appearing to be the major regulator on complex polysaccharides. Our study contributes to understanding of the complex regulatory mechanisms responsible for plant polysaccharide-degrading gene expression, and opens new possibilities for the engineering of fungi able to produce more efficient enzymatic cocktails to be used in biofuel production.

  7. The Role of Selected Flavonols in Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor–1 (TRAIL-R1 Expression on Activated RAW 264.7 Macrophages

    Directory of Open Access Journals (Sweden)

    Monika Warat

    2015-01-01

    Full Text Available Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptors (TRAIL-R are an important factor of apoptosis in cancer cells. There are no data about the effect of flavonols on the receptor expression on a surface of macrophage like cells. In this study, the expression level of TRAIL-R1 on murine RAW264.7 macrophages in the presence of selected flavonols: galangin, kaempferol, kaempferide and quercetin, which differ from their phenyl ring substituents, were studied. The expression of TRAIL-R1 death receptors on non-stimulated and lipopolysaccharide (LPS-stimulated macrophages was determined using flow cytometry. The results suggested that compounds being tested can modulate TRAIL-R1 expression and can enhance TRAIL-mediated apoptosis.

  8. R graphics

    CERN Document Server

    Murrell, Paul

    2005-01-01

    R is revolutionizing the world of statistical computing. Powerful, flexible, and best of all free, R is now the program of choice for tens of thousands of statisticians. Destined to become an instant classic, R Graphics presents the first complete, authoritative exposition on the R graphical system. Paul Murrell, widely known as the leading expert on R graphics, has developed an in-depth resource that takes nothing for granted and helps both neophyte and seasoned users master the intricacies of R graphics. After an introductory overview of R graphics facilities, the presentation first focuses

  9. Accelerated evolution of functional plastid rRNA and elongation factor genes due to reduced protein synthetic load after the loss of photosynthesis in the chlorophyte alga Polytoma.

    Science.gov (United States)

    Vernon, D; Gutell, R R; Cannone, J J; Rumpf, R W; Birky, C W

    2001-09-01

    Polytoma obtusum and Polytoma uvella are members of a clade of nonphotosynthetic chlorophyte algae closely related to Chlamydomonas humicola and other photosynthetic members of the Chlamydomonadaceae. Descended from a nonphotosynthetic mutant, these obligate heterotrophs retain a plastid (leucoplast) with a functional protein synthetic system, and a plastid genome (lpDNA) with functional genes encoding proteins required for transcription and translation. Comparative studies of the evolution of genes in chloroplasts and leucoplasts can identify modes of selection acting on the plastid genome. Two plastid genes--rrn16, encoding the plastid small-subunit rRNA, and tufA, encoding elongation factor Tu--retain their functions in protein synthesis after the loss of photosynthesis in two nonphotosynthetic Polytoma clades but show a substantially accelerated rate of base substitution in the P. uvella clade. The accelerated evolution of tufA is due, at least partly, to relaxed codon bias favoring codons that can be read without wobble, mainly in three amino acids. Selection for these codons may be relaxed because leucoplasts are required to synthesize fewer protein molecules per unit time than are chloroplasts (reduced protein synthetic load) and thus require a lower rate of synthesis of elongation factor Tu. Relaxed selection due to a lower protein synthetic load is also a plausible explanation for the accelerated rate of evolution of rrn16, but the available data are insufficient to test the hypothesis for this gene. The tufA and rrn16 genes in Polytoma oviforme, the sole member of a second nonphotosynthetic clade, are also functional but show no sign of relaxed selection.

  10. Work-related maternal risk factors and the risk of pregnancy induced hypertension and preeclampsia during pregnancy. The Generation R Study.

    Directory of Open Access Journals (Sweden)

    Jaap Jan Nugteren

    Full Text Available OBJECTIVE: To study the associations between physically demanding work and occupational exposure to chemicals and hypertensive disorders during pregnancy within a large birth cohort study, the Generation R Study. METHODS: Associations between occupational characteristics and hypertensive disorders during pregnancy were studied in 4465 pregnant woman participating in a population-based prospective cohort study from early pregnancy onwards in the Netherlands (2002-2006. Mothers who filled out a questionnaire during mid-pregnancy (response 77% of enrolment, were included if they conducted paid employment, had a spontaneously conceived singleton live born pregnancy, and did not suffer from pre-existing hypertension (n = 4465. Questions on physical demanding work were obtained from the Dutch Musculoskeletal Questionnaire and concerned questions on manually handling loads of 25 kg or more, long periods of standing or walking, night shifts, and working hours. To assess occupational exposure to chemicals, job titles and task descriptions were linked to a job-exposure-matrix (JEM, an expert judgment on exposure to chemicals at the workplace. Information on hypertensive disorders during pregnancy was obtained from medical records. RESULTS: We observed no consistent associations between any of the work related risk factors, such as long periods of standing or walking, heavy lifting, night shifts, and working hours, nor exposure to chemicals with hypertensive disorders during pregnancy. CONCLUSION: This prospective birth cohort study suggests that there is no association of hypertensive disorders during pregnancy with physically demanding work or exposure to chemicals. However, the low prevalence of PIH and PE, combined with the low prevalence of occupational risk factors limit the power for inference and larger studies are needed to corroborate or refute these findings.

  11. Small marine craft emission factors observed from the NOAA R/V Ronald H. Brown during TexAQS/GoMACCS 2006

    Science.gov (United States)

    Lerner, B. M.; Lack, D.; Murphy, P. C.; Williams, E. J.

    2007-12-01

    During the TexAQS/GoMACCS 2006 field campaign, the NOAA R/V Ronald H. Brown often encountered small marine recreational craft and small fishing vessels while sailing close to the Texas coast, especially in Galveston Bay. Measurement of a suite of trace gases at high time resolution (1 Hz) allowed us to calculate emission factors (EFs), relative to carbon dioxide, for nitrogen oxides (NOx), sulfur dioxide (SO2) and carbon monoxide (CO) for distinct exhaust plumes from these sources. Photoacoustic aerosol absorption spectroscopy (PAS) measurements made concurrently allowed for the first quantification of mass EFs for light-absorbing particles from fishing craft. As previously observed along the New England coast, gasoline-powered recreational vessels showed significantly higher NOx/CO2 and lower CO/CO2 EFs than current emissions inventories predict, although in agreement with the most recent published literature of laboratory studies. These findings imply lower volatile organic compound emissions from these vessels, although this was not directly measured.

  12. [{sup 99m}Tc(CO){sub 3}]{sup +}-(HE){sub 3}-Z{sub IGF1R:4551}, a new Affibody conjugate for visualization of insulin-like growth factor-1 receptor expression in malignant tumours

    Energy Technology Data Exchange (ETDEWEB)

    Orlova, Anna; Varasteh, Zohreh [Uppsala University, Preclinical PET Platform, Department of Medicinal Chemistry, Uppsala (Sweden); Hofstroem, Camilla; Graeslund, Torbjoern [Royal Institute of Technology, Division of Molecular Biotechnology, School of Biotechnology, Stockholm (Sweden); Strand, Joanna [Uppsala University, Division of Biomedical Radiation Sciences, Uppsala (Sweden); Sandstrom, Mattias [Uppsala University Hospital, Medical Physics, Department of Oncology, Uppsala (Sweden); Andersson, Karl [Uppsala University, Division of Biomedical Radiation Sciences, Uppsala (Sweden); Ridgeview Instruments AB, Uppsala (Sweden); Tolmachev, Vladimir [Uppsala University, Division of Biomedical Radiation Sciences, Uppsala (Sweden); Uppsala University, Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden)

    2013-03-15

    Radionuclide imaging of insulin-like growth factor type 1 receptor (IGF-1R) expression in tumours might be used for selection of patients who would benefit from IGF-1R-targeted therapy. We have previously shown the feasibility of IGF-1R imaging using the Affibody molecule {sup 111}In-DOTA-His{sub 6}-Z{sub IGF1R:4551}. The use of {sup 99m}Tc instead of {sup 111}In should improve sensitivity and resolution of imaging, and reduce the dose burden to patients. We hypothesized that inclusion of a HEHEHE tag instead of a His{sub 6} tag in Z{sub IGF1R:4551} would permit its convenient purification using IMAC, enable labelling with [{sup 99m}Tc(CO){sub 3}]{sup +}, and improve its biodistribution. Z{sub IGF1R:4551} was expressed with a HEHEHE tag in the N terminus. The resulting (HE){sub 3}-Z{sub IGF1R:4551} construct was labelled with [{sup 99m}Tc(CO){sub 3}]{sup +}. Targeting of IGF-1R-expressing cells using [{sup 99m}Tc(CO){sub 3}]{sup +}-(HE){sub 3}-Z{sub IGF1R:4551} was evaluated in vitro and in vivo. (HE){sub 3}-Z{sub IGF1R:4551} was stably labelled with {sup 99m}Tc with preserved specific binding to IGF-1R-expressing DU-145 prostate cancer cells in vitro. In mice, [{sup 99m}Tc(CO){sub 3}]{sup +}-(HE){sub 3}-Z{sub IGF1R:4551} accumulated in IGF-1R-expressing organs (pancreas, stomach, lung and salivary gland). [{sup 99m}Tc(CO){sub 3}]{sup +}-(HE){sub 3}-Z{sub IGF1R:4551} demonstrated 3.6-fold lower accumulation in the liver and spleen than {sup 111}In-DOTA-Z{sub IGF1R:4551}. In NMRI nu/nu mice with DU-145 prostate cancer xenografts, the tumour uptake was 1.32 {+-} 0.11 %ID/g and the tumour-to-blood ratio was 4.4 {+-} 0.3 at 8 h after injection. The xenografts were visualized using a gamma camera 6 h after injection. [{sup 99m}Tc(CO){sub 3}]{sup +}-(HE){sub 3}-Z{sub IGF1R:4551} is a promising candidate for visualization of IGF-1R expression in malignant tumours. (orig.)

  13. AT2R -1332 G:A polymorphism and its interaction with AT1R 1166 A:C, ACE I/D and MMP-9 -1562 C:T polymorphisms: risk factors for susceptibility to preeclampsia.

    Science.gov (United States)

    Rahimi, Zohreh; Rahimi, Ziba; Aghaei, Amir; Vaisi-Raygani, Asad

    2014-03-15

    The possible association of angiotensin type 2 receptor (AT2R) -1332 G:A polymorphism with susceptibility to preeclampsia was studied in 252 women consisted of 155 women with preeclampsia and 97 healthy pregnant women. Also, the interaction of this polymorphism with angiotensin type 1 receptor (AT1R) 1166 A:C, angiotensin converting enzyme insertion/deletion (ACE I/D) and also with matrix metalloproteinase-9 (MMP-9) -1562 C:T polymorphism was investigated. The AT2R -1332 G:A polymorphism was detected using PCR-RFLP method. Significantly higher frequencies of GG+GA genotype and G allele of AT2R were observed in mild (80.2%, p=0.003 and 47.5%, p=0.012, respectively) and severe (77.8%, p=0.034 and 48.1%, p=0.026, respectively) preeclampsia compared to controls (60.8% and 35.1%, respectively). The presence of G allele was associated with 1.69-fold increased risk of preeclampsia (p=0.005). In severe preeclamptic women, systolic and diastolic blood pressures in the presence of GG+GA genotype were significantly higher compared to those in the presence of AA genotype. The concomitant presence of both alleles of AT2R G and AT1R C was associated with 1.3 times increased risk of mild preeclampsia (p=0.03). There was an interaction between AT2R G and ACE D alleles that significantly increased the risk of mild and severe preeclampsia by 1.38- and 1.3-fold, respectively. Also, interaction between MMP-9 T and AT2R G alleles increased the risk of severe preeclampsia 1.39-fold (p=0.028). Our study demonstrated that the G allele of AT2R -1332 G:A polymorphism is associated with an increased risk of preeclampsia. Also, epistatic interaction of G allele and each allele of the AT1R C, ACE D and MMP-9 T was associated with the risk of preeclampsia. Our findings suggest that the renin-angiotensin system (RAS) variants and gene-gene interactions affect the risk of preeclampsia.

  14. Cloning and Function Analysis of Transcription Factor Gene NtGRAS-R1 from Nicotiana tabacum L.%烟草转录因子基因NtGRAS-R1的克隆与功能分析

    Institute of Scientific and Technical Information of China (English)

    李富欣; 许芳芳; 李素敏; 肖万福; 孙艳敏; 刘卫群; 郭红祥

    2015-01-01

    为了分析NtGRAS-R1的生物学功能,在NCBI上BLAST植物的EST数据库拼接获得Nt-GRAS-R1的全长序列;根据该序列设计特异引物,利用PCR方法从烟草根系cDNA 中扩增Nt-GRAS-R1,将其连接到pS1300表达载体上,采用农杆菌介导的花序侵染法转化拟南芥,采用RT-PCR法检测转基因拟南芥植株;获得稳定转基因拟南芥后观察生长性状,并用qPCR方法检测At-CLV3基因的表达情况。结果显示,NtGRAS-R1基因属于HAM亚家族,编码508个氨基酸;观察发现,转基因拟南芥植株根长和根体积明显大于野生型;qPCR结果表明,转基因拟南芥AtCLV3的表达量明显低于野生型拟南芥。初步表明NtGRAS-R1参与根系生长发育调控过程。%The aim of this research is to explore the function of NtGRAS-R1 . The full-length sequence of NtGRAS-R1 was acquired with in silico cloning method. The ORF fragment of NtGRAS-R1 was obtained with PCR amplification method, and then pS1300-NtGRAS-R1 expression vector was constructed. Transgenic Arabidopsis with NtGRAS-R1 was obtained with Agrobacterium tumefaciens-mediated floral dip transformation method. RT-PCR was used to identify transgenic plants. The phenotypic of transgenic Arabidopsis was observed, and the expression of AtCLV3 was detected with qPCR method. The results showed that NtGRAS-R1 belonged to HAM subfamily,having an ORF of 1 527 bp to encode a protein of 508 amino acids. Compared to wild type plants, the root length and volume of transgenic Arabidopsis obviously increased. The expression of AtCLV3 in transgenic Arabidopsis was lower than wild type plant. In the present study, NtGRAS-R1 was successfully cloned, and the phenotypic analysis of transgenic Arabidopsis shows that NtGRAS-R1 has a role in the process of tobacco roots growth and development.

  15. Immunolocalization of corticotropin-releasing factor (CRF) and corticotropin-releasing factor receptor 2 (CRF-R2) in the developing gut of the sea bass (Dicentrarchus labrax L.).

    Science.gov (United States)

    Mola, Lucrezia; Gambarelli, Andrea; Pederzoli, Aurora

    2011-05-01

    Our previous data indicated an important role for adrenocorticotropic (ACTH)-like molecules co-operating with macrophages to control the modifications in body homeostasis during the first period of the life of sea bass (up to 30 days post-hatching) before the lymphoid cells have reached complete maturation. The aim of the study was to determine the immunolocalization of corticotropin-releasing factor (CRF), which is a very important mediator of stress-related responses. Our data showed that immunostaining for CRF is localized already at 8 days after hatching in nerve fibers of the gastrointestinal tract wall from the pharynx to the anterior gut, when the larvae are still feeding on yolk. This pattern of immunolocalization appeared similar to that in 24-day-old larvae, but at this stage there were also large cells immunopositive to CRF located in the wall of the midgut and hindgut. Lipopolysaccharide (LPS) treatment, which is a known stimulator of stress hormone responses, did not modify the CRF immunostaining pattern, though it did affect the immunolocalization of the peripheral CRF receptor, i.e. CRF-R2. Immunolocalization of CRF-R2 appeared in nerve fibers of the gut wall in larvae fixed 1h after the end of lipopolysaccharide (LPS) treatment. The present results suggest that CRF plays important autocrine and/or paracrine roles in the early immune responses at the gut level in the larval stages of sea bass (Dicentrarchus labrax L.) as already proposed for ACTH. Moreover, our studies taken together with other research on fish, in comparison with mammals, suggest a phylogenetically old role of CRF in immune-endocrine interactions.

  16. miR-191 May Regulate Pig Preadipocyte Differentiation by Targeting The Transcription Factor C/EBPβ%miR-191通过调控C/EBPβ转录影响猪前体脂肪细胞分化

    Institute of Scientific and Technical Information of China (English)

    刘帅; 宁小敏; 李美航; 仇杨; 李艳杰; 董培越; 杨公社

    2013-01-01

    对实验室前期Solexa结果进行深入挖掘,结合生物信息学分析从不同发育阶段猪皮下脂肪组织差异表达的miRNAs中筛选出高丰度差异极显著的候选miR-191.采用腺病毒过表达miR-191,实时定量PCR、Western blot及双荧光素酶报告基因检测等技术方法,初步研究miR-191对猪前体脂肪细胞分化的影响.结果发现,miR-191随着猪前体脂肪细胞的分化表达量逐渐增加.与对照组相比,过表达miR-191的猪前体脂肪细胞中miR-191转录本显著增加,并引起CCAAT增强子结合蛋白β(C/EBPβ)、PPARγ和aP2的mRNA水平降低,抑制了猪前体脂肪细胞分化.同时,Western blot结果显示,与对照组相比过表达miR-191的猪前体脂肪细胞在48 h C/EBPβ蛋白水平下降了55%.更重要的是,通过TargetScan等算法正向筛选以及MicroInspector反向筛选联合获得miR-191候选靶基因,经双荧光素酶报告基因检测结果证实,miR-191可直接作用于C/EBPβ 3'UTR,从而降低萤火虫荧光素酶活性.综上所述,miR-191可能通过抑制脂肪细胞分化早期标志基因C/EBPβ的表达,从而抑制了猪前体脂肪细胞的分化.%Based on our previous solexa sequencing data, combining with bioinformatics analysis of microRNA expression changes in porcine adipose tissue from different growth phases in a model of obesity, we found the expression level of miR-191 was significantly different in developing swine adipose tissue. In this research, we successfully overexpressed miR-191's transcripts by recombinant adenovirus in primary cultured porcine preadipocytes, and then investigated the impact on differentiation of pig preadipocyte by Real-time quantitative PCR, Western blot. The results showed that miR-191's expression level gradually increased during differentiation. The miR-191 transcripts increased dramatically when miR-191 overexpressed compared to the control group, which caused the decrease of C/EBPp, PPARy and aP2's mRNA level and the

  17. Local pulmonary administration of factor VIIa (rFVIIa in diffuse alveolar hemorrhage (DAH – a review of a new treatment paradigm

    Directory of Open Access Journals (Sweden)

    Nielsen JD

    2012-03-01

    without thromboembolic complication when FVIIa was administered locally via the air side, because the FVIIa does not penetrate the alveolo-capillary membrane to the blood-side. The incidence of DAH (in the US and Europe is 100,000–150,000, and 50,000 patients annually are at risk of developing DAH following hematopoietic stem cell transplant (HSCT and autoimmune diseases. Finally 50,000–100,000 patients may be falsely categorized as having acute respiratory distress syndrome/acute lung injury (ARDS/ALI because DAH and ARDS cannot be separated clinically. A new treatment paradigm of DAH is proposed as no other intervention has been able to ensure pulmonary hemostasis in DAH. The diagnosis of DAH is simple, a series of broncho-alveolar washes which become increasingly bloody. This test should be performed in all patients with pulmonary opacities in order to separate ARDS/ALI from DAH. FVIIa administrated via pulmonary route is "drug of choice", because it stops bleeding in the life-threatening syndrome DAH. Hemostasis is obtained after only one to two small doses of FVIIa (50 µg/kg body weight per dose and after hemostasis the oxygen transport quickly improves.Conclusion: Intrapulmonary administration of rFVIIa is recommended as the treatment of choice for DAH and blast lung injury (BLI because the treatment has been shown to be successful and uncomplicated in spite of the fact that only a small series of DAH has been documented.Keywords: coagulation factor FVIIa, diffuse alveolar hemorrhage, hemosiderosis, blast lung injury, local pulmonary treatment, biologics, bronchoalveolar lavage, diagnosis, algorithm, new treatment recommendation

  18. Tumor Targeting Using Anti–Epidermal Growth Factor Receptor (ior egf/r3 Immunoconjugate with a Tetraaza Macrocyclic Agent (DO3A-EA

    Directory of Open Access Journals (Sweden)

    Gauri Mishra

    2012-09-01

    Full Text Available Epidermal growth factor receptor (EGFR signaling inhibition represents a highly promising arena for the application of molecularly targeted cancer therapies. EGFR conjugated metal chelates have been proposed as potential imaging agents for cancers that overexpress EGFR receptors. Through improved understanding of EGFR biology in human cancers, there is anticipation that more tumor-selective therapy approaches with diminished collateral normal tissue toxicity can be advanced. We report here on the results with a thermodynamically stable chelate, 1,4,7-tris(carboxymethyl-10-(2-aminoethyl-1,4,7,10-tetraazacyclododecane (DO3A-EA and anti-EGFr (ior egf/r3 conjugate to develop immunospecifc imaging agent. Conjugation and labelling with anti-EGFr was performed using standard procedure and subjected to purification on size exclusion chromatography. The conjugated antibodies were labeled with a specific activity 20-30 mCi/mg of protein. Labeling efficiencies were measured by ascending paper chromatography on ITLC-SG strips. Radiolabeling of the immunoconjugate was found to be 98.5 ± 0.30%. 99mTc-DO3A-EA-EGFr conjugate was studied in athymic mice bearing U-87MG, MDA-MB-468 tumors following intravenous injection. Pharmacokinetic and biodistribution studies confirmed long circulation times (t1/2(fast= 45 min and t1/2(slow=4 hours 40 min and efficient accumulation in tumors. Biodistribution studies in athymic mice grafted with U-87MG human glioblastoma multiforme and Hela human cervical carcinoma tumors revealed significant localization of 99mTc-labeled antibodies conjugate in tumors and reduced accumulation in normal organs. This new chelating agent is promising for immunoscintigraphy since good tumour-to-normal organ contrast could be demonstrated. These properties can be exploited for immunospecifc contrast agents in nuclear medicine and SPECT imaging.

  19. [Study of the polymorphism R353Q in the coagulation factor VII gene and the N700S in the thrombospondin-1 gene in young patients with acute myocardial infarction].

    Science.gov (United States)

    Valades-Mejía, María Guadalupe; Domínguez-López, María Lilia; Aceves-Chimal, José Luis; Miranda, Alfredo Leaños; Majluf-Cruz, Abraham; Isordia-Salas, Irma

    2014-01-01

    Antecedentes: el infarto agudo de miocardio es la principal causa de morbilidad y mortalidad en el mundo, y resulta de la combinación de factores modificables y genéticos. Se ha propuesto que el polimorfismo R353Q en el gen del factor VII de la coagulación representa un factor protector en contra del infarto agudo de miocardio, mientras que el polimorfismo N700S en el gen de la trombospondina-1 (TSP- 1) incrementa el riesgo; sin embargo, los resultados aún suscitan controversia. Objetivo: determinar la posible asociación de los polimorfismos R353Q y del N700S con el infarto agudo de miocardio en pacientes mexicanos menores de 45 años. Material y métodos: estudio de casos y controles que incluyó 252 pacientes con diagnóstico de infarto agudo de miocardio y 252 individuos aparentemente sanos sin antecedentes de enfermedad coronaria, pareados por edad y sexo. Los polimorfismos R353Q N700S se determinaron en todos los participantes por medio de PCR-RFLP. Resultados: no se observó diferencia estadística en la distribución genotípica del polimorfismo R353Q del FVII entre los grupos con infarto agudo de miocardio y el grupo control (p = 0.06). Se encontró una distribución genotípica similar del polimorfismo N700S en ambos grupos (p = 0.50). Se identificaron como factores de riesgo independiente para infarto agudo de miocardio: hipertensión arterial, diabetes mellitus, antecedentes heredofamiliares para enfermedad coronaria y dislipidemia. Conclusiones: los polimorfismos R353Q y N700S no representan un factor protector o de riesgo, respectivamente, para infarto agudo de miocardio en pacientes jóvenes mexicanos. Palabras clave: factor VII de la coagulación, trombospondina-1, infarto agudo de miocardio, polimorfismo.

  20. Determinant factors for hybridmyeloma culture (H9r9 in the yield of anti - D – impact of medium (IMDM and RPMI, serum (FCS and cell density

    Directory of Open Access Journals (Sweden)

    Sathya R

    2008-12-01

    empirical informations of H9r9 cell metabolism to achieve optimization. Keywords: Hybridoma (H9r9, Foetal calf serum (FCS, Anti – D, Apoptosis, IMDM/RPMI Medium Received: 12 January 2009 / Received in revised form: 6 February 2009, Accepted: 25 February 2009, Published online: 28 February 2009

  1. PTS regulation domain-containing transcriptional activator CelR and sigma factor σ(54) control cellobiose utilization in Clostridium acetobutylicum.

    Science.gov (United States)

    Nie, Xiaoqun; Yang, Bin; Zhang, Lei; Gu, Yang; Yang, Sheng; Jiang, Weihong; Yang, Chen

    2016-04-01

    The phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) regulation domain (PRD)-containing enhancer binding proteins (EBPs) are an important class of σ(54) -interacting transcriptional activators. Although PRD-containing EBPs are present in many Firmicutes, most of their regulatory functions remain unclear. In this study, the transcriptional regulons of about 50 PRD-containing EBPs in diverse Firmicutes species are reconstructed by using a comparative genomic approach, which contain the genes associated with utilization of β-glucosides, fructose/levan, mannose/glucose, pentitols, and glucosamine/fructosamine. We then present experimental evidence that the cel operon involved in cellobiose utilization is directly regulated by CelR and σ(54) (SigL) in Clostridium acetobutylicum. The predicted three CelR-binding sites and σ(54) promoter elements upstream of the cel operon are verified by in vitro binding assays. We show that CelR has an ATPase activity, which is strongly stimulated by the presence of DNA containing the CelR-binding sites. Moreover, mutations in any one of the three CelR-binding sites significantly decreased the cel promoter activity probably due to the need for all three DNA sites for maximal ATPase activity of CelR. It is suggested that CelR is regulated by PTS-mediated phosphorylation at His-551 and His-829, which exerts a positive effect and an inhibitory effect, respectively, on the CelR activity. © 2015 John Wiley & Sons Ltd.

  2. 基于分位数回归的我国R&D经费投入影响因素的动态研究%A Dynamic Analysis of Influence Factors on China's R&D Investment Based on the Quantile Regression Model

    Institute of Scientific and Technical Information of China (English)

    谢兰云; 王维国

    2012-01-01

    Our R&D investment is less and R&D intensity is low, these conditions have strictly limited our innovational capability. The paper uses stepwise least squares regression to determine the major factors based on what-if of the influence factors about Chinese R&D investment, then uses quantile regression model to study the dynamic changes of their impact on R&D investment on different quantile. We find that the influence of government R&D investment is more stable. With the increase in R&D investment, the effect of economic development is gradually reducing and the effect of industrial structure is gradually increasing. Based on these, the paper has some advices about the policy of increasing R&D investment.%针对我国R&D投入较少,R&D强度较低的现状,在对影响我国R&D投入因素进行假设分析的基础上,利用逐步回归方法对相关影响因素进行了筛选,得出经济发展水平、政府科技投入和产业结构是影响我国科技投入的主要因素,然后利用分位数回归模型对我国R&D投入在不同分位点上各影响因素的作用进行了详细的研究,研究发现政府科技投入的影响较稳定,随R&D投入的增多经济发展水平对其的影响在逐渐减少,而产业结构对其的影响则在逐渐增大,最后在此基础上提出了提高我国R&D投入的相关政策建议.

  3. Cross-talk between the epidermal growth factor-like repeats/fibronectin 6-8 repeats domains of Tenascin-R and microglia modulates neural stem/progenitor cell proliferation and differentiation.

    Science.gov (United States)

    Liao, Hong; Huang, Wenhui; Niu, Rui; Sun, Lixin; Zhang, Luyong

    2008-01-01

    Mounting evidence has demonstrated that the microenvironment of stem/progenitor cells plays an important role in their proliferation and commitment to their fate. However, it remains unclear how all elements, such as astrocytes, microglia, extracellular matrix molecules, soluble factors, and their cross-talk interactions in the microenvironments, affect neural stem/progenitor cell fate. This work explored the influences of cross-talk between Tenascin-R (TN-R) and microglia on neural stem/progenitor cell proliferation and differentiation. Our results show that microglia triggered by TN-R distinct domains EGF-like repeats (EGFL) and fibronectin 6-8 repeats (FN6-8) significantly enhanced the proliferation of neural stem/progenitor cells and also obviously induced the differentiation into neurons but not oligodendrocytes. Neurite processes of neurons generated from neural progenitor cells were promoted by both EGFL and FN6-8 domains-activated microglia. Microglia triggered by EGFL and FN6-8 secreted brain-derived neurotrophic factor (BDNF) and transforming growth factor-beta (TGF-beta); interestingly, FN6-8 could activate microglia to secrete nerve growth factor in addition to BDNF and TGF-beta, but EGFL domain could not. All these data implied that the cross-talk between TN-R distinct domains EGFL/FN6-8 and microglia promoted neural stem/progenitor cell proliferation and induced their differentiation into neurons.

  4. The Research on China's Regional Industrial Productivity Differences about R & D Factors%中国工业生产率区域差异的R & D因素研究

    Institute of Scientific and Technical Information of China (English)

    孙赵勇; 任保平

    2014-01-01

    The expanding of regional differences of Chinese industrial productivity leads regional economic grows unbalanced. In this surroudings, we estimated industrial productivity of 31 provinces and cities of China in this pa-per. Industrial technology among provinces shows significant spatial dependence. We examined the influence of R&D with the method of seemingly unrelated Regression (SUR), panel space and spatial lag model (SLM) and spatial error model (SEM). The results show that China's R&D investment more easily lead to capital deepening labor-biased technological innovation. We can draw the conclusion that conclusions of this study to promote inno-vation and industrial transformation and upgrading of the industrial structure of China's technology has important policy implications.%中国工业生产率区域差异持续扩大,导致区域经济难以均衡增长。在此背景下,估算了中国31个省市的工业生产率偏移的资本产出差异项和劳动产出差异项,发现各省市的工业技术特征具有明显的空间依赖性。分别使用似不相关估计(SUR)和空间面板的空间滞后模型(SLM)以及空间误差模型(SEM),检验了我国R&D投入对工业生产率的作用机制。研究结果表明,我国R&D投入更容易引致资本深化的劳动偏向型技术创新,劳动资源丰富的地区不能通过R&D投入取得竞争优势;而资本市场发达的地区从R&D投入中更容易获得技术优势。

  5. Detection of myxoma viruses encoding a defective M135R gene from clinical cases of myxomatosis; possible implications for the role of the M135R protein as a virulence factor

    DEFF Research Database (Denmark)

    Belsham, Graham; Polacek, Charlotta; Breum, Solvej Østergaard

    2010-01-01

    Background: Myxoma virus is a member of the Poxviridae and causes disease in European rabbits. Laboratory confirmation of the clinical disease, which occurs in the autumn of most years in Denmark, has been achieved previously using antigen ELISA and electron microscopy. Results: An unusually large...... number of clinically suspected cases of myxomatosis were observed in Denmark during 2007. Myxoma virus DNA was detected, using a new real time PCR assay which targets the M029L gene, in over 70% of the clinical samples submitted for laboratory confirmation. Unexpectedly, further analysis revealed......: It appears that expression of the full-length myxoma virus M135R protein is not required for virulence in rabbits. Hence, the frame-shift mutation in the M135R gene in the nonpathogenic 6918 virus strain is not sufficient to explain the attenuation of this myxoma virus but one/some of the other frame...

  6. CovS Simultaneously Activates and Inhibits the CovR-Mediated Repression of Distinct Subsets of Group A Streptococcus Virulence Factor-Encoding Genes▿ †

    OpenAIRE

    Treviño, Jeanette; Perez, Nataly; Ramirez-Peña, Esmeralda; Liu, Zhuyun; Shelburne, Samuel A.; Musser, James M.; Sumby, Paul

    2009-01-01

    To colonize and cause disease at distinct anatomical sites, bacterial pathogens must tailor gene expression in a microenvironment-specific manner. The molecular mechanisms that control the ability of the human bacterial pathogen group A Streptococcus (GAS) to transition between infection sites have yet to be fully elucidated. A key regulator of GAS virulence gene expression is the CovR-CovS two-component regulatory system (also known as CsrR-CsrS). covR and covS mutant strains arise spontaneo...

  7. Work-related maternal risk factors and the risk of pregnancy induced hypertension and Preeclampsia during pregnancy. The generation R study

    NARCIS (Netherlands)

    J.J. Nugteren (Jaap); C.A. Snijder (Claudia); A. Hofman (Albert); V.W.V. Jaddoe (Vincent); E.A.P. Steegers (Eric); A. Burdorf (Alex)

    2012-01-01

    textabstractObjective: To study the associations between physically demanding work and occupational exposure to chemicals and hypertensive disorders during pregnancy within a large birth cohort study, the Generation R Study. Methods: Associations between occupational characteristics and hypertensive

  8. Work-related maternal risk factors and the risk of pregnancy induced hypertension and Preeclampsia during pregnancy. The generation R study

    NARCIS (Netherlands)

    J.J. Nugteren (Jaap); C.A. Snijder (Claudia); A. Hofman (Albert); V.W.V. Jaddoe (Vincent); E.A.P. Steegers (Eric); A. Burdorf (Alex)

    2012-01-01

    textabstractObjective: To study the associations between physically demanding work and occupational exposure to chemicals and hypertensive disorders during pregnancy within a large birth cohort study, the Generation R Study. Methods: Associations between occupational characteristics and hypertensive

  9. MiR-153 targets the nuclear factor-1 family and protects against teratogenic effects of ethanol exposure in fetal neural stem cells

    OpenAIRE

    Pai-Chi Tsai; Shameena Bake; Sridevi Balaraman; Jeremy Rawlings; Holgate, Rhonda R.; Dustin Dubois; Miranda, Rajesh C.

    2014-01-01

    ABSTRACT Ethanol exposure during pregnancy is an established cause of birth defects, including neurodevelopmental defects. Most adult neurons are produced during the second trimester-equivalent period. The fetal neural stem cells (NSCs) that generate these neurons are an important but poorly understood target for teratogenesis. A cohort of miRNAs, including miR-153, may serve as mediators of teratogenesis. We previously showed that ethanol decreased, while nicotine increased miR-153 expressio...

  10. Parallel R

    CERN Document Server

    McCallum, Ethan

    2011-01-01

    It's tough to argue with R as a high-quality, cross-platform, open source statistical software product-unless you're in the business of crunching Big Data. This concise book introduces you to several strategies for using R to analyze large datasets. You'll learn the basics of Snow, Multicore, Parallel, and some Hadoop-related tools, including how to find them, how to use them, when they work well, and when they don't. With these packages, you can overcome R's single-threaded nature by spreading work across multiple CPUs, or offloading work to multiple machines to address R's memory barrier.

  11. R + R$^{2}$ gravity as R + backreaction

    CERN Document Server

    Kung, J H

    1995-01-01

    Quadratic theory of gravity is a complicated constraint system. We investigate some consequences of treating quadratic terms perturbatively (higher derivative version of backreaction effects). This approach is shown to overcome some well known problems associated with higher derivative theories, i.e., the physical gravitational degree of freedom remains unchanged from those of Einstein gravity. Using such an interpretation of R + \\beta R^2 gravity, we investigate a classical and Wheeler DeWitt evolution of R + \\beta R^2 gravity for a particular sign of \\beta, corresponding to non- tachyon case. Matter is described by a phenomenological \\rho \\propto a(t)^{-n}. It is concluded that both the Friedmann potential U(a) ( {\\dot a}^2 + 2U(a) = 0 ) and the Wheeler DeWitt potential W(a) (\\left[-{\\partial^2\\over \\partial a^2} + 2W(a)\\right]\\psi (a) =0 ) develop repulsive barriers near a\\approx 0 for n>4 (i.e., p > {1\\over 3}\\rho ). The interpretations is clear. Repulsive barrier in U(a) implies that a contracting FRW un...

  12. Molecular Basis of Ligand-Dependent Regulation of NadR, the Transcriptional Repressor of Meningococcal Virulence Factor NadA.

    Directory of Open Access Journals (Sweden)

    Alessia Liguori

    2016-04-01

    Full Text Available Neisseria adhesin A (NadA is present on the meningococcal surface and contributes to adhesion to and invasion of human cells. NadA is also one of three recombinant antigens in the recently-approved Bexsero vaccine, which protects against serogroup B meningococcus. The amount of NadA on the bacterial surface is of direct relevance in the constant battle of host-pathogen interactions: it influences the ability of the pathogen to engage human cell surface-exposed receptors and, conversely, the bacterial susceptibility to the antibody-mediated immune response. It is therefore important to understand the mechanisms which regulate nadA expression levels, which are predominantly controlled by the transcriptional regulator NadR (Neisseria adhesin A Regulator both in vitro and in vivo. NadR binds the nadA promoter and represses gene transcription. In the presence of 4-hydroxyphenylacetate (4-HPA, a catabolite present in human saliva both under physiological conditions and during bacterial infection, the binding of NadR to the nadA promoter is attenuated and nadA expression is induced. NadR also mediates ligand-dependent regulation of many other meningococcal genes, for example the highly-conserved multiple adhesin family (maf genes, which encode proteins emerging with important roles in host-pathogen interactions, immune evasion and niche adaptation. To gain insights into the regulation of NadR mediated by 4-HPA, we combined structural, biochemical, and mutagenesis studies. In particular, two new crystal structures of ligand-free and ligand-bound NadR revealed (i the molecular basis of 'conformational selection' by which a single molecule of 4-HPA binds and stabilizes dimeric NadR in a conformation unsuitable for DNA-binding, (ii molecular explanations for the binding specificities of different hydroxyphenylacetate ligands, including 3Cl,4-HPA which is produced during inflammation, (iii the presence of a leucine residue essential for dimerization and

  13. Molecular Basis of Ligand-Dependent Regulation of NadR, the Transcriptional Repressor of Meningococcal Virulence Factor NadA.

    Science.gov (United States)

    Liguori, Alessia; Malito, Enrico; Lo Surdo, Paola; Fagnocchi, Luca; Cantini, Francesca; Haag, Andreas F; Brier, Sébastien; Pizza, Mariagrazia; Delany, Isabel; Bottomley, Matthew J

    2016-04-01

    Neisseria adhesin A (NadA) is present on the meningococcal surface and contributes to adhesion to and invasion of human cells. NadA is also one of three recombinant antigens in the recently-approved Bexsero vaccine, which protects against serogroup B meningococcus. The amount of NadA on the bacterial surface is of direct relevance in the constant battle of host-pathogen interactions: it influences the ability of the pathogen to engage human cell surface-exposed receptors and, conversely, the bacterial susceptibility to the antibody-mediated immune response. It is therefore important to understand the mechanisms which regulate nadA expression levels, which are predominantly controlled by the transcriptional regulator NadR (Neisseria adhesin A Regulator) both in vitro and in vivo. NadR binds the nadA promoter and represses gene transcription. In the presence of 4-hydroxyphenylacetate (4-HPA), a catabolite present in human saliva both under physiological conditions and during bacterial infection, the binding of NadR to the nadA promoter is attenuated and nadA expression is induced. NadR also mediates ligand-dependent regulation of many other meningococcal genes, for example the highly-conserved multiple adhesin family (maf) genes, which encode proteins emerging with important roles in host-pathogen interactions, immune evasion and niche adaptation. To gain insights into the regulation of NadR mediated by 4-HPA, we combined structural, biochemical, and mutagenesis studies. In particular, two new crystal structures of ligand-free and ligand-bound NadR revealed (i) the molecular basis of 'conformational selection' by which a single molecule of 4-HPA binds and stabilizes dimeric NadR in a conformation unsuitable for DNA-binding, (ii) molecular explanations for the binding specificities of different hydroxyphenylacetate ligands, including 3Cl,4-HPA which is produced during inflammation, (iii) the presence of a leucine residue essential for dimerization and conserved in

  14. Differences between disease-associated endoplasmic reticulum aminopeptidase 1 (ERAP1) isoforms in cellular expression, interactions with tumour necrosis factor receptor 1 (TNF-R1) and regulation by cytokines.

    Science.gov (United States)

    Yousaf, N; Low, W Y; Onipinla, A; Mein, C; Caulfield, M; Munroe, P B; Chernajovsky, Y

    2015-05-01

    Endoplasmic reticulum aminopeptidase 1 (ERAP1) processes peptides for major histocompatibility complex (MHC) class I presentation and promotes cytokine receptor ectodomain shedding. These known functions of ERAP1 may explain its genetic association with several autoimmune inflammatory diseases. In this study, we identified four novel alternatively spliced variants of ERAP1 mRNA, designated as ΔExon-11, ΔExon-13, ΔExon-14 and ΔExon-15. We also observed a rapid and differential modulation of ERAP1 mRNA levels and spliced variants in different cell types pretreated with lipopolysaccharide (LPS). We have studied three full-length allelic forms of ERAP1 (R127-K528, P127-K528, P127-R528) and one spliced variant (ΔExon-11) and assessed their interactions with tumour necrosis factor receptor 1 (TNF-R1) in transfected cells. We observed variation in cellular expression of different ERAP1 isoforms, with R127-K528 being expressed at a much lower level. Furthermore, the cellular expression of full-length P127-K528 and ΔExon-11 spliced variant was enhanced significantly when co-transfected with TNF-R1. Isoforms P127-K528, P127-R528 and ΔExon-11 spliced variant associated with TNF-R1, and this interaction occurred in a region within the first 10 exons of ERAP1. Supernatant-derived vesicles from transfected cells contained the full-length and ectodomain form of soluble TNF-R1, as well as carrying the full-length ERAP1 isoforms. We observed marginal differences between TNF-R1 ectodomain levels when co-expressed with individual ERAP1 isoforms, and treatment of transfected cells with tumour necrosis factor (TNF), interleukin (IL)-1β and IL-10 exerted variable effects on TNF-R1 ectodomain cleavage. Our data suggest that ERAP1 isoforms may exhibit differential biological properties and inflammatory mediators could play critical roles in modulating ERAP1 expression, leading to altered functional activities of this enzyme.

  15. Research of the External Environment Influencing Factors of Regional R & D Expenditures with the Background of Innovation Network--Empirical Analysis Based on Provincial Panel Data%创新网络背景下区域R & D支出的外部环境影响因素研究--基于省际面板数据的实证检验

    Institute of Scientific and Technical Information of China (English)

    黄攸立; 费雪雪

    2015-01-01

    After the formation of innovation networks, innovation subjects’ R&D expenditures are affected not only by the external environment, but also other subjects. The sum of their R&D expenditures constitutes the core of regional R&D expenditures on the macro-level. By establishing the mathematical model by using results of existing researches for reference, we study on the influencing factors of regional R&D expenditures with the background of innovation network, use the panel data method to test 2000-2009 sample data of 30 provinces, and then discover that the government’s investment in science and technology impacts the regional R&D expenditures not very significantly negative, while market size, market structure, openness and technical import all impact the R&D expenditures positively, and the influence decreases one by one. The results in this paper have great theoretical significance and practical value on the resource allocation and innovation performance.%创新网络形成后,区域内各创新主体的R&D支出与其他主体的行为息息相关,其R&D支出的总和在宏观上表现为区域R&D支出的核心内容。以此为背景,基于现有研究成果,构建数学模型,采用面板数据模型对2000~2009年的30个省市样本数据进行检验,研究区域R&D支出的外部环境影响因素。结果显示:在创新网络背景下,市场规模、市场结构、开放度以及技术引进等因素与区域R&D支出水平正相关,且相关程度依次递减;政府投入负向影响区域R&D支出,但影响的显著性水平并不高。研究成果对实现区域资源优化配置,提高区域创新绩效具有一定的理论意义和实用价值。

  16. Nuclear Factor κB is Required for Tumor Growth Inhibition Mediated by Enavatuzumab (PDL192), a Humanized Monoclonal Antibody to TweakR.

    Science.gov (United States)

    Purcell, James W; Kim, Han K; Tanlimco, Sonia G; Doan, Minhtam; Fox, Melvin; Lambert, Peter; Chao, Debra T; Sho, Mien; Wilson, Keith E; Starling, Gary C; Culp, Patricia A

    2014-01-01

    TweakR is a TNF receptor family member, whose natural ligand is the multifunctional cytokine TWEAK. The growth inhibitory activity observed following TweakR stimulation in certain cancer cell lines and the overexpression of TweakR in many solid tumor types led to the development of enavatuzumab (PDL192), a humanized IgG1 monoclonal antibody to TweakR. The purpose of this study was to determine the mechanism of action of enavatuzumab's tumor growth inhibition and to provide insight into the biology behind TweakR as a cancer therapeutic target. A panel of 105 cancer lines was treated with enavatuzumab in vitro; and 29 cell lines of varying solid tumor backgrounds had >25% growth inhibition in response to the antibody. Treatment of sensitive cell lines with enavatuzumab resulted in the in vitro and in vivo (xenograft) activation of both classical (p50, p65) and non-classical (p52, RelB) NFκB pathways. Using NFκB DNA binding functional ELISAs and microarray analysis, we observed increased activation of NFκB subunits and NFκB-regulated genes in sensitive cells over that observed in resistant cell lines. Inhibiting NFκB subunits (p50, p65, RelB, p52) and upstream kinases (IKK1, IKK2) with siRNA and chemical inhibitors consistently blocked enavatuzumab's activity. Furthermore, enavatuzumab treatment resulted in NFκB-dependent reduction in cell division as seen by the activation of the cell cycle inhibitor p21 both in vitro and in vivo. The finding that NFκB drives the growth inhibitory activity of enavatuzumab suggests that targeting TweakR with enavatuzumab may represent a novel cancer treatment strategy.

  17. Nuclear Factor κB is required for tumor growth inhibition mediated by enavatuzumab (PDL192, a humanized monoclonal antibody to TweakR

    Directory of Open Access Journals (Sweden)

    James W. Purcell

    2014-01-01

    Full Text Available TweakR is a TNF receptor family member, whose natural ligand is the multifunctional cytokine TWEAK. The growth inhibitory activity observed following TweakR stimulation in certain cancer cell lines and the overexpression of TweakR in many solid tumor types led to the development of enavatuzumab (PDL192, a humanized IgG1 monoclonal antibody to TweakR. The purpose of this study was to determine the mechanism of action of enavatuzumab’s tumor growth inhibition and to provide insight into the biology behind TweakR as a cancer therapeutic target. A panel of 105 cancer lines was treated with enavatuzumab in vitro; and 29 cell lines of varying solid tumor backgrounds had >25% growth inhibition in response to the antibody. Treatment of sensitive cell lines with enavatuzumab resulted in the in vitro and in vivo (xenograft activation of both classical (p50, p65 and non-classical (p52, RelB NFκB pathways. Using NFκB DNA binding functional ELISAs and microarray analysis, we observed increased activation of NFκB subunits and NFκB regulated genes in sensitive cells over that observed in resistant cell lines. Inhibiting NFκB subunits (p50, p65, RelB, p52 and upstream kinases (IKK1, IKK2 with siRNA and chemical inhibitors consistently blocked enavatuzumab’s activity. Furthermore, enavatuzumab treatment resulted in NFκB-dependent reduction in cell-division as seen by the activation of the cell cycle inhibitor p21 both in vitro and in vivo. The finding that NFκB drives the growth inhibitory activity of enavatuzumab suggests that targeting TweakR with enavatuzumab may represent a novel cancer treatment strategy.

  18. Two trypanosome-specific proteins are essential factors for 5S rRNA abundance and ribosomal assembly in Trypanosoma brucei.

    Science.gov (United States)

    Hellman, Kristina M; Ciganda, Martin; Brown, Silvia V; Li, Jinlei; Ruyechan, William; Williams, Noreen

    2007-10-01

    We have previously identified and characterized two novel nuclear RNA binding proteins, p34 and p37, which have been shown to bind 5S rRNA in Trypanosoma brucei. These two proteins are nearly identical, with one major difference, an 18-amino-acid insert in the N-terminal region of p37, as well as three minor single-amino-acid differences. Homologues to p34 and p37 have been found only in other trypanosomatids, suggesting that these proteins are unique to this ancient family. We have employed RNA interference (RNAi) studies in order to gain further insight into the interaction between p34 and p37 with 5S rRNA in T. brucei. In our p34/p37 RNAi cells, decreased expression of the p34 and p37 proteins led to morphological alterations, including loss of cell shape and vacuolation, as well as to growth arrest and ultimately to cell death. Disruption of a higher-molecular-weight complex containing 5S rRNA occurs as well as a dramatic decrease in 5S rRNA levels, suggesting that p34 and p37 serve to stabilize 5S rRNA. In addition, an accumulation of 60S ribosomal subunits was observed, accompanied by a significant decrease in overall protein synthesis within p34/p37 RNAi cells. Thus, the loss of the trypanosomatid-specific proteins p34 and p37 correlates with a diminution in 5S rRNA levels as well as a decrease in ribosome activity and an alteration in ribosome biogenesis.

  19. (R-Doxylaminium (R,R-tartrate

    Directory of Open Access Journals (Sweden)

    A.S. Dayananda

    2012-04-01

    Full Text Available In the title compound (systematic name: (R-dimethyl{2-[1-phenyl-1-(pyridin-2-ylethoxy]ethyl}azanium (R,R-3-carboxy-2,3-dihydroxypropanoate, C17H23N2O+·C4H5O6−, the doxylaminium cation is protonated at the N atom. The tartrate monoanions are linked by short, almost linear O—H...O hydrogen bonds into chains extended along [100]. These chains are interlinked by anion–pyridine O—H...N hydrogen bonds into a two-dimensional grid structure. WeakC—H...O interactions also play a role in the crystal packing. An intramolecular hydroxy–carboxylate O—H...O hydrogen bond influences the conformation of the anion: the hydrogen-bonded fragment is almost planar, the maximum deviation from the mean plane being 0.059 (14 Å. In the cation, the aromatic rings are almost perpendicular [dihedral angle = 84.94 (8°] and the conformation of the O—C—C—N chain is gauche(−, the dihedral angle is −76.6 (2°. The absolute configuration was assigned on the basis of known chirality of the parent compound.

  20. 基于竞合视角的产学R&D联盟发展过程的影响因素研究%Research on the Influencing Factors of the Developing Process of Collaborative R&D Union of Industry-University Based on the Co-opetition Perspective

    Institute of Scientific and Technical Information of China (English)

    黄攸立; 王茜; 洪嵩

    2013-01-01

    竞合理论认为价值创造的本质是合作,价值分配的本质是竞争.产学R&D联盟的发展是双方共同投入人力资金创造价值,共同分享R&D成果分配价值的过程,即大学、产业两个彼此独立的实体为创造价值而合作,同时为了自身利益最大化而竞争,这种竞合关系存在于联盟过程的始终.当前学者们尚未从竞合角度对产学R&D联盟进行分析,因此,本文通过梳理相关国内外文献,从竞合的视角分析产学R&D联盟发展中的各种影响因素,并构建其路径发展模型.%Based on co-opetition theory, cooperation is considered as the essence of value creation, and competition is the essence of value distribution. In the development of collaborative R&D unit of Industry-University, they input resource to create value and share the R&D achievement to distribute value, namely, they cooperate for creating the value and compete for maximizing the benefit, and the co-opetition relationship will exist in the union from beginning to the end. However, there is no scholar analysis on R&D union of Industry-University from co-opetition perspective. In this paper, after reviewing the related literatures, we analyzed the influencing factors of the Industry-University R&D union during the process of developing based on the co-opetition assumption, and then established the model for this process.

  1. The R2R3 MYB transcription factor PavMYB10.1 involves in anthocyanin biosynthesis and determines fruit skin colour in sweet cherry ( Prunus avium L.)

    OpenAIRE

    Jin, Wanmei; Wang, Hua; Li, Maofu; Wang, Jing; Yang, Yuan; Zhang, Xiaoming; Yan, Guohua; Zhang, Hong; Liu, Jiashen; Zhang, Kaichun

    2016-01-01

    Summary Sweet cherry is a diploid tree species and its fruit skin has rich colours from yellow to blush to dark red. The colour is closely related to anthocyanin biosynthesis and is mainly regulated at the transcriptional level by transcription factors that regulate the expression of multiple structural genes. However, the genetic and molecular bases of how these genes ultimately determine the fruit skin colour traits remain poorly understood. Here, our genetic and molecular evidences identif...

  2. miR-204 Shifts the Epithelial to Mesenchymal Transition in Concert with the Transcription Factors RUNX2, ETS1, and cMYB in Prostate Cancer Cell Line Model

    Directory of Open Access Journals (Sweden)

    Krassimira Todorova

    2014-01-01

    Full Text Available Epithelial to mesenchymal transition is an essential step in advanced cancer development. Many master transcription factors shift their expression to drive this process, while noncoding RNAs families like miR-200 are found to restrict it. In this study we investigated how the tumor suppressor miR-204 and several transcription factors modulate main markers of mesenchymal transformation like E- and N-cadherin, SLUG, VEGF, and SOX-9 in prostate cancer cell line model (LNCaP, PC3, VCaP, and NCI-H660. We found that SLUG, E-cadherin, and N-cadherin are differentially modulated by miR-204, using miR-204 specific mimics and inhibitors and siRNA gene silencing (RUNX2, ETS-1, and cMYB. The genome perturbation associated TMPRSS2-ERG fusion coincided with shift from tumor-suppressor to tumor-promoting activity of this miRNA. The ability of miR-204 to suppress cancer cell viability and migration was lost in the fusion harboring cell lines. We found differential E-cadherin splicing corroborating to miR-204 modulatory effects. RUNX2, ETS1, and cMYB are involved in the regulation of E-cadherin, N-cadherin, and VEGFA expression. RUNX2 knockdown results in SOX9 downregulation, while ETS1 and cMYB silencing result in SOX9 upregulation in VCaP cells. Their expression was found to be also methylation dependent. Our study provides means for understanding cancer heterogeneity in regard to adapted therapeutic approaches development.

  3. The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease

    DEFF Research Database (Denmark)

    Lill, Christina M; Rengmark, Aina; Pihlstrøm, Lasse;

    2015-01-01

    A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Here we...

  4. Adult Life-Span Patterns in WAIS-R Block Design Performance: Cross-Sectional versus Longitudinal Age Gradients and Relations to Demographic Factors

    Science.gov (United States)

    Ronnlund, Michael; Nilsson, Lars-Goran

    2006-01-01

    Aging patterns in WAIS-R Block Design Test (BDT) were examined cross-sectionally and longitudinally. One sample (35-80 years, n=1000) was assessed in 1988-1990 and five years later (836 returned). An independent cohort-matched sample (n=974) was assessed at Time 2 to control for practice effects. Relations between BDT, gender, and education were…

  5. WAIS-R Factors and Performance on the Luria-Nebraska's Intelligence, Memory, and Motor Scales: A Canonical Model of Relationships.

    Science.gov (United States)

    Fowler, Patrick C.; Macciocchi, Stephen N.

    1986-01-01

    Pattern and level of performance on the WAIS-R (Wechsler Adult Intelligence Scale Revised) and the Luria-Nebraska's Intelligence, Memory, and Motor Scales were examined for 93 neurologically impaired adults. Each set of procedures evidently is indexing the same theoretical constructs. (Author/ABB)

  6. WAIS-R Factors and Performance on the Luria-Nebraska's Intelligence, Memory, and Motor Scales: A Canonical Model of Relationships.

    Science.gov (United States)

    Fowler, Patrick C.; Macciocchi, Stephen N.

    1986-01-01

    Pattern and level of performance on the WAIS-R (Wechsler Adult Intelligence Scale Revised) and the Luria-Nebraska's Intelligence, Memory, and Motor Scales were examined for 93 neurologically impaired adults. Each set of procedures evidently is indexing the same theoretical constructs. (Author/ABB)

  7. The LacI–Family Transcription Factor, RbsR, Is a Pleiotropic Regulator of Motility, Virulence, Siderophore and Antibiotic Production, Gas Vesicle Morphogenesis and Flotation in Serratia

    Directory of Open Access Journals (Sweden)

    Chin M. Lee

    2017-09-01

    Full Text Available Gas vesicles (GVs are proteinaceous, gas-filled organelles used by some bacteria to enable upward movement into favorable air/liquid interfaces in aquatic environments. Serratia sp. ATCC39006 (S39006 was the first enterobacterium discovered to produce GVs naturally. The regulation of GV assembly in this host is complex and part of a wider regulatory network affecting various phenotypes, including antibiotic biosynthesis. To identify new regulators of GVs, a comprehensive mutant library containing 71,000 insertion mutants was generated by random transposon mutagenesis and 311 putative GV-defective mutants identified. Three of these mutants were found to have a transposon inserted in a LacI family transcription regulator gene (rbsR of the putative ribose operon. Each of these rbsR mutants was GV-defective; no GVs were visible by phase contrast microscopy (PCM or transmission electron microscopy (TEM. GV deficiency was caused by the reduction of gvpA1 and gvrA transcription (the first genes of the two contiguous operons in the GV gene locus. Our results also showed that a mutation in rbsR was highly pleiotropic; the production of two secondary metabolites (carbapenem and prodigiosin antibiotics was abolished. Interestingly, the intrinsic resistance to the carbapenem antibiotic was not affected by the rbsR mutation. In addition, the production of a siderophore, cellulase and plant virulence was reduced in the mutant, whereas it exhibited increased swimming and swarming motility. The RbsR protein was predicted to bind to regions upstream of at least 18 genes in S39006 including rbsD (the first gene of the ribose operon and gvrA. Electrophoretic mobility shift assays (EMSA confirmed that RbsR bound to DNA sequences upstream of rbsD, but not gvrA. The results of this study indicate that RbsR is a global regulator that affects the modulation of GV biogenesis, but also with complex pleiotropic physiological impacts in S39006.

  8. Research on the Factors Influencing Psychological Capital of R&D Staff%企业研发人员心理资本的影响因素研究

    Institute of Scientific and Technical Information of China (English)

    李永周; 方婧婧

    2013-01-01

    基于企业研发人员的问卷调查数据,使用方差分析和多元线性回归分析的方法对研发人员心理资本的影响因素做了归纳和深入分析,得到企业研发人员心理资本及其各维度的关键影响因素和回归方程,并在此基础上提出开发企业研发人员心理资本的建议.%Based on the questionnaire survey data of R&D staff,the paper uses analysis of variance and multivariate linear regression to research on the influencing factors of psychological capital of R&D staff.We obtain the key influencing factors,the regression equation of psychological capital and its dimension of R&D staff,and put forward suggestions to develop R&D staff' s psychological capital on this basis.

  9. Active G protein-coupled receptors (GPCR), matrix metalloproteinases 2/9 (MMP2/9), heparin-binding epidermal growth factor (hbEGF), epidermal growth factor receptor (EGFR), erbB2, and insulin-like growth factor 1 receptor (IGF-1R) are necessary for trenbolone acetate-induced alterations in protein turnover rate of fused bovine satellite cell cultures.

    Science.gov (United States)

    Thornton, K J; Kamanga-Sollo, E; White, M E; Dayton, W R

    2016-06-01

    Trenbolone acetate (TBA), a testosterone analog, increases protein synthesis and decreases protein degradation in fused bovine satellite cell (BSC) cultures. However, the mechanism through which TBA alters these processes remains unknown. Recent studies indicate that androgens improve rate and extent of muscle growth through a nongenomic mechanism involving G protein-coupled receptors (GPCR), matrix metalloproteinases (MMP), heparin-binding epidermal growth factor (hbEGF), the epidermal growth factor receptor (EGFR), erbB2, and the insulin-like growth factor-1 receptor (IGF-1R). We hypothesized that TBA activates GPCR, resulting in activation of MMP2/9 that releases hbEGF, which activates the EGFR and/or erbB2. To determine whether the proposed nongenomic pathway is involved in TBA-mediated alterations in protein turnover, fused BSC cultures were treated with TBA in the presence or absence of inhibitors for GPCR, MMP2/9, hbEGF, EGFR, erbB2, or IGF-1R, and resultant protein synthesis and degradation rates were analyzed. Assays were replicated at least 9 times for each inhibitor experiment utilizing BSC cultures obtained from at least 3 different steers that had no previous exposure to steroid compounds. As expected, fused BSC cultures treated with 10 n TBA exhibited increased ( BSC cultures with 10 n TBA in the presence of inhibitors for GPCR, MMP2/9, hbEGF, EGFR, erbB2, or IGF-1R suppressed ( 0.05) effect on TBA-mediated decreases in protein degradation. However, inhibition of both EGFR and erbB2 in the presence of 10 n TBA resulted in decreased ( BSC cultures treated with 10 n TBA exhibit increased ( BSC cultures.

  10. Regulation of the cyanobacterial CO2-concentrating mechanism involves internal sensing of NADP+ and α-ketogutarate levels by transcription factor CcmR.

    Directory of Open Access Journals (Sweden)

    Shawn M E Daley

    Full Text Available Inorganic carbon is the major macronutrient required by organisms utilizing oxygenic photosynthesis for autotrophic growth. Aquatic photoautotrophic organisms are dependent upon a CO(2 concentrating mechanism (CCM to overcome the poor CO(2-affinity of the major carbon-fixing enzyme, ribulose-bisphosphate carboxylase/oxygenase (Rubisco. The CCM involves the active transport of inorganic forms of carbon (C(i into the cell to increase the CO(2 concentration around the active site of Rubisco. It employs both bicarbonate transporters and redox-powered CO(2-hydration enzymes coupled to membranous NDH-type electron transport complexes that collectively produce C(i concentrations up to a 1000-fold greater in the cytoplasm compared to the external environment. The CCM is regulated: a high affinity CCM comprised of multiple components is induced under limiting external Ci concentrations. The LysR-type transcriptional regulator CcmR has been shown to repress its own expression along with structural genes encoding high affinity C(i transporters distributed throughout the genome of Synechocystis sp. PCC 6803. While much has been learned about the structural genes of the CCM and the identity of the transcriptional regulators controlling their expression, little is known about the physiological signals that elicit the induction of the high affinity CCM. Here CcmR is studied to identify metabolites that modulate its transcriptional repressor activity. Using surface plasmon resonance (SPR α-ketoglutarate (α-KG and the oxidized form of nicotinamide adenine dinucleotide phosphate (NADP(+ have been identified as the co-repressors of CcmR. Additionally, ribulose-1,5-bisphosphate (RuBP and 2-phosphoglycolate (2-PG have been confirmed as co-activators of CmpR which controls the expression of the ABC-type bicarbonate transporter.

  11. Determining the Number of Factors to Retain in EFA: Using the SPSS R-Menu v2.0 to Make More Judicious Estimations

    Science.gov (United States)

    Courtney, Matthew Gordon Ray

    2013-01-01

    Exploratory factor analysis (EFA) is a common technique utilized in the development of assessment instruments. The key question when performing this procedure is how to best estimate the number of factors to retain. This is especially important as under- or over-extraction may lead to erroneous conclusions. Although recent advancements have been…

  12. Determining the Number of Factors to Retain in EFA: Using the SPSS R-Menu v2.0 to Make More Judicious Estimations

    Science.gov (United States)

    Courtney, Matthew Gordon Ray

    2013-01-01

    Exploratory factor analysis (EFA) is a common technique utilized in the development of assessment instruments. The key question when performing this procedure is how to best estimate the number of factors to retain. This is especially important as under- or over-extraction may lead to erroneous conclusions. Although recent advancements have been…

  13. Experimental study on the miR126 inhibition of vascular endothelial growth factor expression in esophageal squamous cell carcinoma%miR126抑制食管鳞癌血管内皮生长因子表达的实验研究*

    Institute of Scientific and Technical Information of China (English)

    汪建超; 张晖; 朱金海; 彭德峰; 朱正志; 马小开; 姚廷敬

    2013-01-01

      目的:探讨miR126与血管内皮生长因子在食管鳞癌中的表达及关系,以及其对食管鳞癌细胞系的影响。方法:随机选取2011年3月至2011年4月间手术治疗的食管鳞癌患者手术标本4例,,取癌组织及癌旁正常黏膜。提取肿瘤及正常癌旁组织microRNA,逆转录后用实时定量PCR的方法检测miR126的表达情况;提取标本中的mRNA和蛋白用实时定量PCR和Western blot的方法检测VEGF的表达;培养TE-1细胞系并转染miR126模拟体,检测miR126对TE-1细胞增殖和VEGF表达的影响。结果:与正常组织相比,miR126在癌组织的表达明显降低;在RNA和蛋白水平,VEGF水平均明显升高;转染miR126模拟体的细胞BrdU掺入量较转染阴性对照的细胞明显增多,VEGF在RNA和蛋白水平上均明显降低。结论:在食管鳞癌组织中miR126水平下调,VEGF表达增高;miR126可抑制TE-1细胞的增殖,其抑制细胞增殖的作用可能是通过下调VEGF的表达而实现的。%Objective:This study aimed to explore miR126 expression and its relationship with vascular endothelial growth factor (VEGF) in esophageal squamous cell carcinoma, as well as the effect of miR126 expression on an esophageal carcinoma cell line. Methods: Four patients with esophageal squamous cell carcinoma were randomly selected in our hospital from 2011.3 to 2011.4. Tumor and normal tumor-adjacent tissue specimens were collected from the patients, and miRNA was extracted. The expression of miR126 was detected by real-time quantitative PCR. Furthermore, total mRNA and protein were extracted to detect VEGF expression by real-time quantitative PCR and Western blot analysis. miR126-like mRNA was then transfected to the TE-1 cell line to determine its effect on the proliferation of TE-1 cells and VEGF expression. Results: miR126 expression was significantly downregulated in esophageal carcinoma tissues compared with normal esophageal tissues. By

  14. Experimental Determination of the Recovery Factor and Analytical Solution of the Conical Flow Field for a 20 deg Included Angle Cone at Mach Numbers of 4.6 and 6.0 and Stagnation Temperatures to 2600 degree R

    Science.gov (United States)

    Pfyl, Frank A.; Presley, Leroy L.

    1961-01-01

    The local recovery factor was determined experimentally along the surface of a thin-walled 20 deg included angle cone for Mach numbers near 6.0 at stagnation temperatures between 1200 deg R and 2600 deg R. In addition, a similar cone configuration was tested at Mach numbers near 4.5 at stagnation temperatures of approximately 612 deg R. The local Reynolds number based on flow properties at the edge of the boundary layer ranged between 0.1 x 10(exp 4) and 3.5 x 10(exp 4) for tests at temperatures above 1200 deg R and between 6 x 10(exp 4) and 25 x 10(exp 4) for tests at temperatures near 612 deg R. The results indicated, generally, that the recovery factor can be predicted satisfactorily using the square root of the Prandtl number. No conclusion could be made as to the necessity of evaluating the Prandtl number at a reference temperature given by an empirical equation, as opposed to evaluating the Prandtl number at the wall temperature or static temperature of the gas at the cone surface. For the tests at temperatures above 1200 deg R (indicated herein as the tests conducted in the slip-flow region), two definite trends in the recovery data were observed - one of increasing recovery factor with decreasing stagnation pressure, which was associated with slip-flow effects and one of decreasing recovery factor with increasing temperature. The true cause of the latter trend could not be ascertained, but it was shown that this trend was not appreciably altered by the sources of error of the magnitude considered herein. The real-gas equations of state were used to determine accurately the local stream properties at the outer edge of the boundary layer of the cone. Included in the report, therefore, is a general solution for the conical flow of a real gas using the Beattie-Bridgeman equation of state. The largest effect of temperature was seen to be in the terms which were dependent upon the internal energy of the gas. The pressure and hence the pressure drag terms were

  15. At R407/R408

    CERN Multimedia

    1974-01-01

    R407/R408 were experiments designed by the CERN-Collège de France-Heidelberg-Karlsruhe Collaboration to study two-particle correlations in the fragmentation region requiring a large transverse momentum particle in the forward direction. Atmospheric pressure Cerenkov counters were part of the additional equipment set up during 1974 at the SFM facility. Here Paul Hanke multi-reflected on Cerenkov mirrors.

  16. Determining the Number of Factors to Retain in EFA: Using the SPSS R-Menu v2.0 to Make More Judicious Estimations

    Directory of Open Access Journals (Sweden)

    Matthew Gordon Ray Courtney

    2013-04-01

    Full Text Available Exploratory factor analysis (EFA is a common technique utilized in the development of assessment instruments. The key question when performing this procedure is how to best estimate the number of factors to retain. This is especially important as under- or over-extraction may lead to erroneous conclusions. Although recent advancements have been made to answer the number of factors question, popular statistical packages do not come standard with these modern techniques. This paper details how to program IBM SPSS Statistics software (SPSS to conveniently perform five modern techniques designed to estimate the number of factors to retain. By utilizing the five empirically-supported techniques illustrated in this article, researchers will be able to more judiciously model data.

  17. Predictive factors for difficult mask ventilation in the obese surgical population [v1; ref status: indexed, http://f1000r.es/4i9

    Directory of Open Access Journals (Sweden)

    Davide Cattano

    2014-10-01

    Full Text Available Background Difficult Mask Ventilation (DMV, is a situation in which it is impossible for an unassisted anesthesiologist to maintain oxygen saturation >90% using 100% oxygen and positive pressure ventilation to prevent or reverse signs of inadequate ventilation during mask ventilation.  The incidence varies from 0.08 – 15%. Patient-related anatomical features are by far the most significant cause.  We analyzed data from an obese surgical population (BMI> 30 kg/m2 to identify specific risk and predictive factors for DMV. Methods Five hundred and fifty seven obese patients were identified from a database of 1399 cases associated with preoperative airway examinations where mask ventilation was attempted. Assessment of mask ventilation in this group was stratified by a severity score (0-3, and a step-wise selection method was used to identify independent predictors.  The area under the curve of the receiver-operating-characteristic was then used to evaluate the model’s predictive value. Adjusted odds ratios and their 95% confidence intervals were also calculated. Results DMV was observed in 80/557 (14% patients. Three independent predictive factors for DMV in obese patients were identified: age 49 years, short neck, and neck circumference  43 cm. In the current study th sensitivity for one factor is 0.90 with a specificity 0.35. However, the specificity increased to 0.80 with inclusion of more than one factor. Conclusion According to the current investigation, the three predictive factors are strongly associated with DMV in obese patients. Each independent risk factor alone provides a good screening for DMV and two factors substantially improve specificity. Based on our analysis, we speculate that the absence of at least 2 of the factors we identified might have a significant negative predictive value and can reasonably exclude DMV, with a negative likelihood ratio 0.81.

  18. On the output factor measurements of the CyberKnife iris collimator small fields: Experimental determination of the k{sub Q{sub c{sub l{sub i{sub n,Q{sub m{sub s{sub r}{sup f{sub c}{sub l}{sub i}{sub n},f{sub m}{sub s}{sub r}}}}}}}}} correction factors for microchamber and diode detectors

    Energy Technology Data Exchange (ETDEWEB)

    Pantelis, E.; Moutsatsos, A.; Zourari, K.; Petrokokkinos, L.; Sakelliou, L.; Kilby, W.; Antypas, C.; Papagiannis, P.; Karaiskos, P.; Georgiou, E.; Seimenis, I. [Medical Physics Laboratory, Medical School, University of Athens, 75 Mikras Asias, 115 27 Athens (Greece) and CyberKnife Center, Iatropolis-MagnitikiTomografia, 54-56 Ethnikis-Antistaseos, 152 31 Athens (Greece); Medical Physics Laboratory, Medical School, University of Athens, 75 Mikras Asias, 115 27 Athen (Greece); Nuclear and Particle Physics Section, Physics Department, University of Athens, Panepistimioupolis, Ilisia, 157 71 Athens (Greece); Accuray Incorporated, Sunnyvale, California 94089 (United States); 1st Department of Radiology, Aretaieion Hospital, Medical School, University of Athens, Vas. Sophias, 115 28 Athens (Greece) and CyberKnife Center, Iatropolis-MagnitikiTomografia, 54-56 Ethnikis-Antistaseos, 152 31 Athens (Greece); Medical Physics Laboratory, Medical School, University of Athens, 75 Mikras Asias, 115 27 Athens (Greece); Medical Physics Laboratory, Medical School, Democritus University of Thrace, 2nd Building of Preclinical Section, University Campus, 68100 Alexandroupolis (Greece)

    2012-08-15

    Purpose: To measure the output factors (OFs) of the small fields formed by the variable aperture collimator system (iris) of a CyberKnife (CK) robotic radiosurgery system, and determine the k{sub Q{sub c{sub l{sub i{sub n,Q{sub m{sub s{sub r}{sup f{sub c}{sub l}{sub i}{sub n},f{sub m}{sub s}{sub r}}}}}}}}} correction factors for a microchamber and four diode detectors. Methods: OF measurements were performed using a PTW PinPoint 31014 microchamber, four diode detectors (PTW-60017, -60012, -60008, and the SunNuclear EDGE detector), TLD-100 microcubes, alanine dosimeters, EBT films, and polymer gels for the 5 mm, 7.5 mm, 10 mm, 12.5 mm, and 15 mm iris collimators at 650 mm, 800 mm, and 1000 mm source to detector distance (SDD). The alanine OF measurements were corrected for volume averaging effects using the 3D dose distributions registered in polymer gel dosimeters. k{sub Q{sub c{sub l{sub i{sub n,Q{sub m{sub s{sub r}{sup f{sub c}{sub l}{sub i}{sub n},f{sub m}{sub s}{sub r}}}}}}}}} correction factors for the PinPoint microchamber and the diode dosimeters were calculated through comparison against corresponding polymer gel, EBT, alanine, and TLD results. Results: Experimental OF results are presented for the array of dosimetric systems used. The PinPoint microchamber was found to underestimate small field OFs, and a k{sub Q{sub c{sub l{sub i{sub n,Q{sub m{sub s{sub r}{sup f{sub c}{sub l}{sub i}{sub n},f{sub m}{sub s}{sub r}}}}}}}}} correction factor ranging from 1.127 {+-} 0.022 (for the 5 mm iris collimator) to 1.004 {+-} 0.010 (for the 15 mm iris collimator) was determined at the reference SDD of 800 mm. The PinPoint k{sub Q{sub c{sub l{sub i{sub n,Q{sub m{sub s{sub r}{sup f{sub c}{sub l}{sub i}{sub n},f{sub m}{sub s}{sub r}}}}}}}}} correction factor was also found to increase with decreasing SDD; k{sub Q{sub c{sub l{sub i{sub n,Q{sub m{sub s{sub r}{sup f{sub c}{sub l}{sub i}{sub n},f{sub m}{sub s}{sub r}}}}}}}}} values equal to 1.220 {+-} 0.028 and 1.077 {+-} 0

  19. Procédé de suralcalinisation d'additifs détergents : rôle des promoteurs et détermination du régime de la réaction de surbasage Overbasing Process of Detergent Additives: Behavior of Promoters and Determination of Factors Controling the Reaction

    Directory of Open Access Journals (Sweden)

    Gallo R.

    2006-11-01

    Full Text Available Le mécanisme du procédé de suralcalinisation des huiles lubrifiantes est étudié. L'analyse du contrôle physique et (ou chimique est effectué dans ce procédé polyphasique, où une base solide (chaux, magnésie en suspension dans une solution, constituée d'une microémulsion, est carbonatée. Le carbonate non colloïdal est formé dans le milieu par une réaction successive à celle de la formation de carbonate colloïdal. La réaction, en présence (et en absence de détergent alkylarylsulfonique, n'est pas limitée par la cinétique chimique, mais par la diffusion des réactifs. Le méthanol, utilisé comme cotensioactif, influe sur la quantité de carbonate colloïdal sans augmenter la vitesse de surbasage. Les essais en milieu anhydre montrent que la présence d'une quantité très faible d'eau est indispensable. L'importance de la dilution par le solvant (xylène et la réactivité comparée MgO/Ca(OH2 sont discutées. Overbased (overalcalinized detergent additives are applied in lubrication of modern combustion engines : they neutralize the acidic products coming from combustion and fight corrosive wear. Overbased calcium sulfonates, the most widely used are made by carbonating CaO or Ca(OH2 in an hydrocarbon mixture (alkane + xylene containing a detergent (mostly alkylaryl-sulfonate and reaction promoters (water, alcohol, amine. The process is operated by several companies and a large amount of patent literature is reported on the subject [2]; however if the geometrical and physical nature of the colloidal carbonare particles formed in the process has been studied, very little is known on the fundamental aspects and on the mechanism of the overbasing process; this is what is described and discussed in this paper. Following previous kinetic results on experimental parameters associated to carbonatation, [4], further data are obtained applying kinetic graphs used in reactor analysis of complex reactions (Fig. 1. Plotting YA

  20. Identification of HIV-1 Epitopes that Induce the Synthesis of a R5 HIV-1 Suppression Factor by Human CD4+ T Cells Isolated from HIV-1 Immunized Hu-PBL SCID Mice

    Directory of Open Access Journals (Sweden)

    Atsushi Yoshida

    2005-01-01

    Full Text Available We have previously reported that immunization of the severe combined immunodeficiency (SCID mice reconstituted with human peripheral blood mononuclear cells (PBMC (hu-PBL-SCID mice with inactivated human immunodeficiency virus type-1 (HIV-1-pulsed-autologous dendritic cells (HIV-DC elicits HIV-1-reactive CD4+ T cells that produce an as yet to be defined novel soluble factor in vitro with anti-viral properties against CCR5 tropic (R5 HIV-1 infection. These findings led us to perform studies designed to identify the lineage of the cell that synthesizes such a factor in vitro and define the epitopes of HIV-1 protein that have specificity for the induction of such anti-viral factor. Results of our studies show that this property is a function of CD4+ but not CD8+ T cells. Human CD4+ T cells were thus recovered from the HIV-DC-immunized hu-PBL-SCID mice and were re-stimulated in vitro by co-culture for 2 days with autologous adherent PBMC as antigen presenting cells, APC previously pulsed with inactivated HIV in IL-2-containing medium to expand HIV-1-reactive CD4+ T cells. Aliquots of these re-stimulated CD4+ T cells were then co-cultured with similar APC's that were previously pulsed with 10 μg/ml of a panel of HIV peptides for an additional 2 days, and their culture supernatants were examined for the production of both the R5 HIV-1 suppression factor and IFN-Υ. The data presented herein show that the HIV-1 primed CD4+ T cells produced the R5 suppression factor in response to a wide variety of HIV-1 gag, env, pol, nef or vif peptides, depending on the donor of the CD4+ T cells. Simultaneous production of human interferon (IFN-Υ was observed in some cases. These results indicate that human CD4+ T cells in PBMC of HIV-1 naive donors have a wide variety of HIV-1 epitope-specific CD4+ T cell precursors that are capable of producing the R5 HIV-1 suppression factor upon DC-based vaccination with whole inactivated HIV-1.

  1. Identification of HIV-1 epitopes that induce the synthesis of a R5 HIV-1 suppression factor by human CD4+ T cells isolated from HIV-1 immunized hu-PBL SCID mice.

    Science.gov (United States)

    Yoshida, Atsushi; Tanaka, Reiko; Kodama, Akira; Yamamoto, Naoki; Ansari, Aftab A; Tanaka, Yuetsu

    2005-12-01

    We have previously reported that immunization of the severe combined immunodeficiency (SCID) mice reconstituted with human peripheral blood mononuclear cells (PBMC) (hu-PBL-SCID mice) with inactivated human immunodeficiency virus type-1 (HIV-1)-pulsed-autologous dendritic cells (HIV-DC) elicits HIV-1-reactive CD4(+) T cells that produce an as yet to be defined novel soluble factor in vitro with anti-viral properties against CCR5 tropic (R5) HIV-1 infection. These findings led us to perform studies designed to identify the lineage of the cell that synthesizes such a factor in vivo and define the epitopes of HIV-1 protein that have specificity for the induction of such anti-viral factor. Results of our studies show that this property is a function of CD4(+) but not CD8(+) T cells. Human CD4(+) T cells were thus recovered from the HIV-DC-immunized hu-PBL-SCID mice and were re-stimulated in vitro by co-culture for 2 days with autologous adherent PBMC as antigen presenting cells, APC previously pulsed with inactivated HIV in IL-2-containing medium to expand HIV-1-reactive CD4(+) T cells. Aliquots of these re-stimulated CD4(+) T cells were then co-cultured with similar APC's that were previously pulsed with 10 microg/ml of a panel of HIV peptides for an additional 2 days, and their culture supernatants were examined for the production of both the R5 HIV-1 suppression factor and IFN-gamma. The data presented herein show that the HIV-1 primed CD4(+) T cells produced the R5 suppression factor in response to a wide variety of HIV-1 gag, env, pol, nef or vif peptides, depending on the donor of the CD4(+) T cells. Simultaneous production of human interferon (IFN)-gamma was observed in some cases. These results indicate that human CD4(+) T cells in PBMC of HIV-1 naive donors have a wide variety of HIV-1 epitope-specific CD4(+) T cell precursors that are capable of producing the R5 HIV-1 suppression factor upon DC-based vaccination with whole inactivated HIV-1.

  2. Early applications of granulocyte colony-stimulating factor (G-CSF) can stabilize the blood-optic-nerve barrier and ameliorate inflammation in a rat model of anterior ischemic optic neuropathy (rAION).

    Science.gov (United States)

    Wen, Yao-Tseng; Huang, Tzu-Lun; Huang, Sung-Ping; Chang, Chung-Hsing; Tsai, Rong-Kung

    2016-10-01

    Granulocyte colony-stimulating factor (G-CSF) was reported to have a neuroprotective effect in a rat model of anterior ischemic optic neuropathy (rAION model). However, the therapeutic window and anti-inflammatory effects of G-CSF in a rAION model have yet to be elucidated. Thus, this study aimed to determine the therapeutic window of G-CSF and investigate the mechanisms of G-CSF via regulation of optic nerve (ON) inflammation in a rAION model. Rats were treated with G-CSF on day 0, 1, 2 or 7 post-rAION induction for 5 consecutive days, and a control group were treated with phosphate-buffered saline (PBS). Visual function was assessed by flash visual evoked potentials at 4 weeks post-rAION induction. The survival rate and apoptosis of retinal ganglion cells were determined by FluoroGold labeling and TUNEL assay, respectively. ON inflammation was evaluated by staining of ED1 and Iba1, and ON vascular permeability was determined by Evans Blue extravasation. The type of macrophage polarization was evaluated using quantitative real-time PCR (qRT-PCR). The protein levels of TNF-α and IL-1β were analyzed by western blotting. A therapeutic window during which G-CSF could rescue visual function and retinal ganglion cell survival was demonstrated at day 0 and day 1 post-infarct. Macrophage infiltration was reduced by 3.1- and 1.6-fold by G-CSF treatment starting on day 0 and 1 post-rAION induction, respectively, compared with the PBS-treated group (Pmodel. © 2016. Published by The Company of Biologists Ltd.

  3. The Role of the Transcription Factors MtrR and MtrA in the Fitness of the Pathogen Neisseria gonorrhoeae

    Science.gov (United States)

    2007-10-19

    regulon to oxidative stress (6). Rob is a larger protein that responds to increasing concentrations of fatty acids or bile salts by binding them, and then...with amido black to show equal loading of the samples. 91 • Figure 11. Expression ofMtrE by wild type and mtrR mutant bacteria E cry Uien ltl ~ en :2...and B. Demple. 1991. Molecular characterization of the soxRS genes of Escherichia coli: two genes control a superoxide stress regulon. Nucleic Acids Res

  4. Measurement of nuclear modification factor $R_\\mathrm{AA}$ in Pb+Pb collisions at $\\sqrt{s_{NN}}=5.02$TeV with the ATLAS detector at the LHC

    CERN Document Server

    The ATLAS collaboration

    2017-01-01

    Measurements of charged hadron spectra and the nuclear modification factor in Pb+Pb collisions at $\\sqrt{s_{NN}}=5.02$TeV with the ATLAS detector at the LHC are presented. The measurements are performed using data with an integrated luminosity of 0.49nb${}^{-1}$ in Pb+Pb collisions and 25pb${}^{-1}$ in pp collisions, obtained in the 2015 LHC physics run. Charged hadron Pb+Pb spectra measured in several centrality intervals are divided by pp spectrum to form the nuclear modification factor, $R_\\mathrm{AA}$, which provides insight into the effects of jet quenching in nuclear collisions. The behavior of $R_\\mathrm{AA}$ is studied as a function of transverse momentum up to 300GeV in different centralities. The values of $R_\\mathrm{AA}$ measured at $\\sqrt{s_{NN}}=5.02$TeV are found to be consistent with the previous measurements at $\\sqrt{s_{NN}}=2.76$TeV published by the ATLAS experiment.

  5. Muscle injection of rAAV/mFIX to secrete clotting factor IX corrects the hemorrhagic tendencies in hemophilia B mice

    Institute of Scientific and Technical Information of China (English)

    陈立; 陈浩明; 陆华中; 吴小兵; 卢大儒; 邱信芳; 薛京伦

    2003-01-01

    Recombinant AAV particles of high titer (>1013 virus genome/mL) were prepared according to the rHSV/AAV helper virus method. After intramuscular injection of viral vectors in the hind limb, a sustained elevated level (>370 ng/mL) of murine FIX expression in the plasma of hemophilia B mouse was detected and persisted for more than 350 days. The biological activity reached 30% of normal levels, and bleeding symptoms in the treated mice were significantly alleviated. No anti-FIX antibody (inhibitor) was detected, though anti-AAV antibodies were found at a very low level after single injection. Repeated injection with rAAV/mFIX led to a variation in anti-AAV antibody levels between the two groups which had received different doses. Results from tissue analysis confirmed the skeletal muscle as the origin for circulating functional mFIX. Our results suggest that AAV-mediated gene transfer offers a promising method of gene therapy for hemophilia B.

  6. Risk factors for otitis media in children with special emphasis on the role of colonization with bacterial airway pathogens: The Generation R study

    NARCIS (Netherlands)

    J.A.M. Labout (Joost); L. Duijts (Liesbeth); A. Lebon (Ankie); R. de Groot (Ronald); A. Hofman (Albert); V.W.V. Jaddoe (Vincent); H.A. Verbrugh (Henri); P.W.M. Hermans (Peter); H.A. Moll (Henriëtte)

    2011-01-01

    textabstractAcute otitis media is the most frequent diagnosis in children visiting physicians' offices. Risk factors for otitis media have been widely studied. Yet, the correlation between bacterial carriage and the development of otitis media is not entirely clear. Our aim was to study in a

  7. Risk factors for otitis media in children with special emphasis on the role of colonization with bacterial airway pathogens: the Generation R study

    NARCIS (Netherlands)

    Labout, J.A.; Duijts, L.; Lebon, A.; Groot, R. de; Hofman, A.; Jaddoe, V.V.; Verbrugh, H.A.; Hermans, P.W.M.; Moll, H.A.

    2011-01-01

    Acute otitis media is the most frequent diagnosis in children visiting physicians' offices. Risk factors for otitis media have been widely studied. Yet, the correlation between bacterial carriage and the development of otitis media is not entirely clear. Our aim was to study in a population-based

  8. The M oderating E ffect of IT Capability on the R elationship between Business Process Reengineering Factors and Organizational Performance of Bank s

    Directory of Open Access Journals (Sweden)

    Kabiru Jinjiri Ringim

    2012-08-01

    Full Text Available The objective of this paper is to investigate the moderating effect of IT capability in the relationship of Business Process Reengineering ( BPR factors and the organizational performance. BPR factors are op erationalized by change management, BPR strategy alignment, customer focus, management commitment, IT investment, and adequate financial resources. The IT capability includes IT knowledge, IT operations and IT objects. Data was collected through a hand - del ivery method by sending questionnaires to 560 banks (Commercial, Microfinance and Mortgage. This study used stratified random samplings proportionate to the numbers of the banks for sample selection. The findings showed that IT capability moderated the re lationship between BPR factors such as change management, customer focus, management commitment and overall organizational performance of the bank. Furthermore, the result revealed that IT capability moderated the relationship between IT investment, manage ment commitment and customer service management performance. The outcome of this study provides important insight to researchers for understanding on the effects of BPR factors and IT capability on organizational performance

  9. The role of prenatal, perinatal and postnatal factors in the explanation of socioeconomic inequalities in preschool asthma symptoms: The generation R study

    NARCIS (Netherlands)

    Hafkamp-de Groen, E.; Rossem, L. van; Jongste, J.C. de; Mohangoo, A.D.; Moll, H.A.; Jaddoe, V.W.V.; Hofman, A.; Mackenbach, J.P.; Raat, H.

    2012-01-01

    Background The authors assessed whether socioeconomic inequalities in asthma symptoms were already present in preschool children and to what extent prenatal, perinatal and postnatal risk factors for asthma symptoms mediate the effect of socioeconomic status (SES). Methods The study included 3136 Dut

  10. R Fluids

    Directory of Open Access Journals (Sweden)

    Caimmi, R.

    2008-06-01

    Full Text Available A theory of collisionless fluids is developed in a unified picture, where nonrotating $(widetilde{Omega_1}=widetilde{Omega_2}= widetilde{Omega_3}=0$ figures with some given random velocity component distributions, and rotating $(widetilde{Omega_1} ewidetilde{Omega_2} e widetilde{Omega_3} $ figures with a different random velocity component distributions, make adjoint configurations to the same system. R fluids are defined as ideal, self-gravitating fluids satisfying the virial theorem assumptions, in presence of systematic rotation around each of the principal axes of inertia. To this aim, mean and rms angular velocities and mean and rms tangential velocity components are expressed, by weighting on the moment of inertia and the mass, respectively. The figure rotation is defined as the mean angular velocity, weighted on the moment of inertia, with respectto a selected axis. The generalized tensor virial equations (Caimmi and Marmo 2005 are formulated for R fluidsand further attention is devoted to axisymmetric configurations where, for selected coordinateaxes, a variation in figure rotation has to be counterbalanced by a variation in anisotropy excess and viceversa. A microscopical analysis of systematic and random motions is performed under a fewgeneral hypotheses, by reversing the sign of tangential or axial velocity components of anassigned fraction of particles, leaving the distribution function and other parametersunchanged (Meza 2002. The application of the reversion process to tangential velocitycomponents is found to imply the conversion of random motion rotation kinetic energy intosystematic motion rotation kinetic energy. The application ofthe reversion process to axial velocity components is found to imply the conversionof random motion translation kinetic energy into systematic motion translation kinetic energy, and theloss related to a change of reference frame is expressed in terms of systematic motion (imaginary rotation kinetic

  11. R fluids

    Directory of Open Access Journals (Sweden)

    Caimmi R.

    2008-01-01

    Full Text Available A theory of collisionless fluids is developed in a unified picture, where nonrotating (Ωf1 = Ωf2 = Ωf3 = 0 figures with some given random velocity component distributions, and rotating (Ωf1 = Ωf2 = Ωf3 figures with a different random velocity component distributions, make adjoint configurations to the same system. R fluids are defined as ideal, self-gravitating fluids satisfying the virial theorem assumptions, in presence of systematic rotation around each of the principal axes of inertia. To this aim, mean and rms angular velocities and mean and rms tangential velocity components are expressed, by weighting on the moment of inertia and the mass, respectively. The figure rotation is defined as the mean angular velocity, weighted on the moment of inertia, with respect to a selected axis. The generalized tensor virial equations (Caimmi and Marmo 2005 are formulated for R fluids and further attention is devoted to axisymmetric configurations where, for selected coordinate axes, a variation in figure rotation has to be counterbalanced by a variation in anisotropy excess and vice versa. A microscopical analysis of systematic and random motions is performed under a few general hypotheses, by reversing the sign of tangential or axial velocity components of an assigned fraction of particles, leaving the distribution function and other parameters unchanged (Meza 2002. The application of the reversion process to tangential velocity components is found to imply the conversion of random motion rotation kinetic energy into systematic motion rotation kinetic energy. The application of the reversion process to axial velocity components is found to imply the conversion of random motion translation kinetic energy into systematic motion translation kinetic energy, and the loss related to a change of reference frame is expressed in terms of systematic motion (imaginary rotation kinetic energy. A number of special situations are investigated in greater

  12. 77 FR 1656 - Proposed Establishment of Restricted Areas R-5402, R-5403A, R-5403B, R-5403C, R-5403D, R-5403E, R...

    Science.gov (United States)

    2012-01-11

    ... Federal Aviation Administration 14 CFR Part 71 RIN 2120-AI92 Proposed Establishment of Restricted Areas R-5402, R-5403A, R- 5403B, R-5403C, R-5403D, R-5403E, R-5403F; Devils Lake, ND AGENCY: Federal Aviation... Areas R-5402, R-5403A, R-5403B, R- 5403C, R-5403D, R-5403E, R-5403F; Devils Lake, ND......

  13. A Regulatory Circuit Composed of a Transcription Factor, IscR, and a Regulatory RNA, RyhB, Controls Fe-S Cluster Delivery

    Directory of Open Access Journals (Sweden)

    Pierre Mandin

    2016-09-01

    Full Text Available Fe-S clusters are cofactors conserved through all domains of life. Once assembled by dedicated ISC and/or SUF scaffolds, Fe-S clusters are conveyed to their apo-targets via A-type carrier proteins (ATCs. Escherichia coli possesses four such ATCs. ErpA is the only ATC essential under aerobiosis. Recent studies reported a possible regulation of the erpA mRNA by the small RNA (sRNA RyhB, which controls the expression of many genes under iron starvation. Surprisingly, erpA has not been identified in recent transcriptomic analysis of the iron starvation response, thus bringing into question the actual physiological significance of the putative regulation of erpA by RyhB. Using an sRNA library, we show that among 26 sRNAs, only RyhB represses the expression of an erpA-lacZ translational fusion. We further demonstrate that this repression occurs during iron starvation. Using mutational analysis, we show that RyhB base pairs to the erpA mRNA, inducing its disappearance. In addition, IscR, the master regulator of Fe-S homeostasis, represses expression of erpA at the transcriptional level when iron is abundant, but depleting iron from the medium alleviates this repression. The conjunction of transcriptional derepression by IscR and posttranscriptional repression by RyhB under Fe-limiting conditions is best described as an incoherent regulatory circuit. This double regulation allows full expression of erpA at iron concentrations for which Fe-S biogenesis switches from the ISC to the SUF system. We further provide evidence that this regulatory circuit coordinates ATC usage to iron availability.

  14. 军工企业研发人员胜任特征要素研究%The Competency Factors of the R&D Personnel in the Military Enterprises

    Institute of Scientific and Technical Information of China (English)

    蒲桂芸; 田怡; 张明亲

    2011-01-01

    Firstly, the current research obtains the competency factors of the R&D personnel through reviewing the literature in previous studies. Subsequently, the author supplements competency factors through behavior event interviews ( BEI), and finally obtains data by administrating questionnaires. In the factorial analysis, five competency factors are identified, which are individual quality, knowledge level, operational capability, achievement motivation and team spirit.These elements are basic to the job analysis, recruitment, training and development, performance management of the R&D personnel in military enterprises.%通过文献分析方法初步获取研发胜任特征要素,通过行为事件访谈法补充研发胜任特征要素,通过问卷调查获取数据,并采用因子分析方法提炼出个人品质、工作能力、团队精神、学识水平、成就动机等5项胜任特征要素.这些要素是军工企业进行研发岗位工作分析、招聘、培训与开发、绩效管理等工作的基础.

  15. Difficult mask ventilation in general surgical population: observation of risk factors and predictors [v1; ref status: indexed, http://f1000r.es/47z

    Directory of Open Access Journals (Sweden)

    Davide Cattano

    2014-08-01

    Full Text Available Background: There are few predictors of difficult mask ventilation and a simple, objective, predictive system to identify patients at risk of difficult mask ventilation does not currently exist. We present a retrospective - subgroup analysis aimed at identifying predictive factors for difficult mask ventilation (DMV in patients undergoing pre-operative airway assessment before elective surgery at a major teaching hospital. Methods: Data for this retrospective analysis were derived from a database of airway assessments, management plans, and outcomes that were collected prospectively from August 2008 to May 2010 at a Level 1 academic trauma center. Patients were stratified into two groups based on the difficulty of mask ventilation and the cohorts were analyzed using univariate analysis and stepwise selection method. Results: A total of 1399 pre-operative assessments were completed with documentation stating that mask ventilation was attempted. Of those 1399, 124 (8.9% patients were found to be difficult to mask ventilate. A comparison of patients with and without difficult mask ventilation identified seven risk factors for DMV: age, body mass index (BMI, neck circumference, history of difficult intubation, presence of facial hair, perceived short neck and obstructive sleep apnea. Although seven risk factors were identified, no individual subject had more than four risk factors. Conclusion: The results of this study confirm that in a real world clinical setting, the incidence of DMV is not negligible and suggest the use of a simple bedside predictive score to improve the accuracy of DMV prediction, thereby improving patient safety. Further prospective studies to validate this score would be useful.

  16. Astrocytes require insulin-like growth factor I to protect neurons against oxidative injury [v1; ref status: indexed, http://f1000r.es/2lf

    Directory of Open Access Journals (Sweden)

    Laura Genis

    2014-01-01

    Full Text Available Oxidative stress is a proposed mechanism in brain aging, making the study of its regulatory processes an important aspect of current neurobiological research. In this regard, the role of the aging regulator insulin-like growth factor I (IGF-I in brain responses to oxidative stress remains elusive as both beneficial and detrimental actions have been ascribed to this growth factor. Because astrocytes protect neurons against oxidative injury, we explored whether IGF-I participates in astrocyte neuroprotection and found that blockade of the IGF-I receptor in astrocytes abrogated their rescuing effect on neurons. The protection mediated by IGF-I against oxidative stress (H2O2 in astrocytes is probably needed for these cells to provide adequate neuroprotection. Indeed, in astrocytes but not in neurons, IGF-I helps decrease the pro-oxidant protein thioredoxin-interacting protein 1 and normalizes the levels of reactive oxygen species. Furthermore, IGF-I cooperates with trophic signals produced by astrocytes in response to H2O2 such as stem cell factor (SCF to protect neurons against oxidative insult. After stroke, a condition associated with brain aging where oxidative injury affects peri-infarcted regions, a simultaneous increase in SCF and IGF-I expression was found in the cortex, suggesting that a similar cooperative response takes place in vivo. Cell-specific modulation by IGF-I of brain responses to oxidative stress may contribute in clarifying the role of IGF-I in brain aging.

  17. Astrocytes require insulin-like growth factor I to protect neurons against oxidative injury [v2; ref status: indexed, http://f1000r.es/38u

    Directory of Open Access Journals (Sweden)

    Laura Genis

    2014-04-01

    Full Text Available Oxidative stress is a proposed mechanism in brain aging, making the study of its regulatory processes an important aspect of current neurobiological research. In this regard, the role of the aging regulator insulin-like growth factor I (IGF-I in brain responses to oxidative stress remains elusive as both beneficial and detrimental actions have been ascribed to this growth factor. Because astrocytes protect neurons against oxidative injury, we explored whether IGF-I participates in astrocyte neuroprotection and found that blockade of the IGF-I receptor in astrocytes abrogated their rescuing effect on neurons. We found that IGF-I directly protects astrocytes against oxidative stress (H2O2. Indeed, in astrocytes but not in neurons, IGF-I decreases the pro-oxidant protein thioredoxin-interacting protein 1 and normalizes the levels of reactive oxygen species. Furthermore, IGF-I cooperates with trophic signals produced by astrocytes in response to H2O2 such as stem cell factor (SCF to protect neurons against oxidative insult. After stroke, a condition associated with brain aging where oxidative injury affects peri-infarcted regions, a simultaneous increase in SCF and IGF-I expression was found in the cortex, suggesting that a similar cooperative response takes place in vivo. Cell-specific modulation by IGF-I of brain responses to oxidative stress may contribute in clarifying the role of IGF-I in brain aging.

  18. Nuevo Modelo para la Determinación del Factor de Fricción en el régimen de flujo turbulento.

    Directory of Open Access Journals (Sweden)

    Yanán Camaraza Medina

    2011-01-01

    Full Text Available En este trabajo se exponen los resultados de la continuidad del proceso investigativo llevado a cabo en el Centro de Estudios de Combustión y Energía , perteneciente a la Facultad de Ingenierías Química y Mecánica de la Universidad de Matanzas, relacionadas con la obtención de modelos adimensionales para la determinación del factor de fricción en el interior de tuberías. La investigación consiste de un análisis de regresión efectuado entre el factor de fricción, el número de Reynolds y la rugosidad relativa, utilizando para este fin datos experimentales reportados por diversos autores, estableciéndose una comparación con la ecuación trascendente del factor de fricción de Colebrook, el modelo más exacto conocido, obteniéndose que no existen diferencias significativas, debido a la alta similitud existente entre los resultados obtenidos a partir de estos modelos en el rango estudiado de los parámetros de trabajo, aunque la divergencia entre los valores experimentales y los obtenidos por el modelo propuesto es ligeramente menor.

  19. A bright side, facet analysis of histrionic personality disorder: the relationship between the HDS Colourful factor and the NEO-PI-R facets in a large adult sample.

    Science.gov (United States)

    Furnham, Adrian

    2014-01-01

    This study looks at "bright-side," Big Five Personality trait correlates of a "dark-side" Personality Disorder, namely Histrionic Personality Disorder (HPD). More than 5000 British adults completed the Neuroticism Extraversion Openness Personality Inventory-Revised (Costa & McCrae, 1985), which measures the Big Five Personality factors at the Domain (Super Factor) and the Facet (Factor) level, as well as the Hogan Development Survey (HDS; Hogan & Hogan, 2009), which has a measure of HPD, exclusively called "Colourful" in the HDS terminology. Correlation and regression results confirmed many of the associations between these "bright" and "dark" side individual difference variables. The Colourful (HPD) score from the HDS was the criterion variable in all analyses. Colourful individuals are high on Extraversion and Openness, but also Stable and disagreeable. The Facet analysis identified Assertiveness and Immodesty as particularly characteristic of that type. The study confirmed work on HPD using different population groups and different measures, showing that personality traits are predictable and correlated with various personality disorders.

  20. Assessment of individual dose utilization vs. physician prescribing recommendations for recombinant activated factor VII (rFVIIa) in paediatric and adult patients with congenital haemophilia and alloantibody inhibitors (CHwI): the Dosing Observational Study in Hemophilia (DOSE).

    Science.gov (United States)

    Gruppo, R A; Kessler, C M; Neufeld, E J; Cooper, D L

    2013-07-01

    Recent data from the Dosing Observational Study in Hemophilia diary study has described home treatment with recombinant activated factor VII (rFVIIa) in congenital haemophilia with inhibitors (CHwI). The current analysis compares prescribed and patient/caregiver-reported rFVIIa administration in paediatric and adult CHwI patients in this study. Patients with ≥ 4 bleeding episodes within a 3-month period prescribed rFVIIa as first-line therapy for bleeding episodes were eligible. Patients/caregivers completed a diary for ≥ 90 days or until the patient experienced four bleeds. Initial, total and mean rFVIIa doses reported for each bleeding episode were calculated and compared with the physician-prescribed doses. Of 52 enrolled patients (25 children; 27 adults), 39 (75%) completed the study. Children and adults had similar mean durations of bleeding episodes. Both patient groups were administered higher initial rFVIIa doses for joint bleeds than prescribed: median (range) 215.2 (74.1-400.0) mcg kg(-1) vs. 200.0 (61.0-270.0) mcg kg(-1) for children, and 231.3 (59.3-379.7) mcg kg(-1) vs. 123.0 (81.0-289.0) mcg kg(-1) for adults. The median infused dose for joint bleeds was higher in adults than children (175.2 vs. 148.0 mcg kg(-1) ), but children received significantly more doses per joint bleed than adults (median 6.5 vs. 3.0). The median total dose per joint bleed was higher in children than adults (1248.7 vs. 441.6). For children and adults, both initial and additional doses administered for bleeds were higher than prescribed. Children received higher total doses per bleed due to an increased number of infusions per bleed.

  1. Teachers’ views on professional image and influential factorsÖğretmenlerin mesleki imajlarina ilişkin görüşleri ve mesleki imaja etki eden faktörler

    Directory of Open Access Journals (Sweden)

    Serkan Ünsal

    2016-09-01

    Full Text Available Nowadays, it is essential for teachers to renew themselves, change and continually pursue excellence. Thus, the core purpose of this study was to determine public and private school teachers’ views on professional image and influential factors. Within this framework, the overall objective of this study was to reveal teachers’ views on professional image, factors influencing this image, teaching profession status, profession dignity, teacher qualification and personal image. The study was based on a qualitative research design. In order to reveal different dimensions of the problem and give voice to different views, the research group was formed by 25 participants on the basis of maximum variation sampling. A semi-structured interview was conducted in the study. The data obtained from interviews were analyzed with descriptive analysis in accordance with semi-structured interview technique. The responses given by participants to each of the questions in interviews were analyzed and grouped in terms of similar and different characteristics. The views obtained from participants are presented in frequency (f and percentage (% on related tables, and their explanatory and indicative views were directly included into the findings. Teacher views based on factors influencing professional image were identified under the sub-theme of political figures as teachers are neglected by the government, and their profession is under-valued. On the other hand, the value and roles appointed to teachers by the Ministry, inconsistencies in education policies, ignorance of teacher views in studies, and forcing teachers into a passive position by over-vindication of students and parents are under the sub-theme of Ministry of National Education (MNE. From the interviews, the participants found teacher qualifications inadequate and considered the status as well as the prestige of the teaching profession to be low.   Özet Bu çalışmanın amacı: s

  2. Dual Control of Sinorhizobium meliloti RpoE2 Sigma Factor Activity by Two PhyR-Type Two-Component Response Regulators▿ †

    OpenAIRE

    Bastiat, Bénédicte; Sauviac, Laurent; Bruand, Claude

    2010-01-01

    RpoE2 is an extracytoplasmic function (ECF) sigma factor involved in the general stress response of Sinorhizobium meliloti, the nitrogen-fixing symbiont of the legume plant alfalfa. RpoE2 orthologues are widely found among alphaproteobacteria, where they play various roles in stress resistance and/or host colonization. In this paper, we report a genetic and biochemical investigation of the mechanisms of signal transduction leading to S. meliloti RpoE2 activation in response to stress. We show...

  3. p.Q192R SNP of PON1 seems not to be Associated with Carotid Atherosclerosis Risk Factors in an Asymptomatic and Normolipidemic Brazilian Population Sample

    Directory of Open Access Journals (Sweden)

    Daniel Zanetti Scherrer

    2015-07-01

    Full Text Available Background:Evidences suggest that paraoxonase 1 (PON1 confers important antioxidant and anti-inflammatory properties when associated with high-density lipoprotein (HDL.Objective:To investigate the relationships between p.Q192R SNP of PON1, biochemical parameters and carotid atherosclerosis in an asymptomatic, normolipidemic Brazilian population sample.Methods:We studied 584 volunteers (females n = 326, males n = 258; 19-75 years of age. Total genomic DNA was extracted and SNP was detected in the TaqMan® SNP OpenArray® genotyping platform (Applied Biosystems, Foster City, CA. Plasma lipoproteins and apolipoproteins were determined and PON1 activity was measured using paraoxon as a substrate. High-resolution β-mode ultrasonography was used to measure cIMT and the presence of carotid atherosclerotic plaques in a subgroup of individuals (n = 317.Results:The presence of p.192Q was associated with a significant increase in PON1 activity (RR = 12.30 (11.38; RQ = 46.96 (22.35; QQ = 85.35 (24.83 μmol/min; p Conclusion:In low-risk individuals, the presence of the p.192Q variant of PON1 is associated with a beneficial plasma lipid profile but not with carotid atherosclerosis.

  4. Verbal Aggression from Care Recipients as a Risk Factor among Nursing Staff: A Study on Burnout in the JD-R Model Perspective.

    Science.gov (United States)

    Viotti, Sara; Gilardi, Silvia; Guglielmetti, Chiara; Converso, Daniela

    2015-01-01

    Among nursing staff, the risk of experiencing violence, especially verbal aggression, is particularly relevant. The present study, developed in the theoretical framework of the Job Demands-Resources model (JD-R), has two main aims: (a) to examine the association between verbal aggression and job burnout in both nurses and nurse's aides and (b) to assess whether job content, social resources, and organizational resources lessen the negative impact of verbal aggression on burnout in the two professional groups. The cross-sectional study uses a dataset that consists of 630 workers (522 nurses and 108 nurse's aides) employed in emergency and medical units. High associations were found between verbal aggression and job burnout in both professional groups. Moderated hierarchical regressions showed that, among nurses, only the job content level resources moderated the effects of the verbal aggression on job burnout. Among nurse's aides, the opposite was found. Some resources on the social and organizational levels but none of the job content level resources buffered the effects of verbal aggression on workers burnout. The study highlights the crucial role of different types of resources in protecting nursing staff from the detrimental effects of verbal aggression on job burnout.

  5. Verbal Aggression from Care Recipients as a Risk Factor among Nursing Staff: A Study on Burnout in the JD-R Model Perspective

    Directory of Open Access Journals (Sweden)

    Sara Viotti

    2015-01-01

    Full Text Available Among nursing staff, the risk of experiencing violence, especially verbal aggression, is particularly relevant. The present study, developed in the theoretical framework of the Job Demands-Resources model (JD-R, has two main aims: (a to examine the association between verbal aggression and job burnout in both nurses and nurse’s aides and (b to assess whether job content, social resources, and organizational resources lessen the negative impact of verbal aggression on burnout in the two professional groups. The cross-sectional study uses a dataset that consists of 630 workers (522 nurses and 108 nurse’s aides employed in emergency and medical units. High associations were found between verbal aggression and job burnout in both professional groups. Moderated hierarchical regressions showed that, among nurses, only the job content level resources moderated the effects of the verbal aggression on job burnout. Among nurse’s aides, the opposite was found. Some resources on the social and organizational levels but none of the job content level resources buffered the effects of verbal aggression on workers burnout. The study highlights the crucial role of different types of resources in protecting nursing staff from the detrimental effects of verbal aggression on job burnout.

  6. Contradicting interplay between insulin-like growth factor-1 and miR-486-5p in primary NK cells and hepatoma cell lines with a contemporary inhibitory impact on HCC tumor progression.

    Science.gov (United States)

    Youness, Rana Ahmed; Rahmoon, Mai Atef; Assal, Reem Amr; Gomaa, Asmaa Ibrahim; Hamza, Mohamed Tarif; Waked, Imam; El Tayebi, Hend Mohamed; Abdelaziz, Ahmed Ihab

    2016-08-01

    In this study, an impaired natural killer (NK) cell cytolytic activity in 135 hepatocellular carcinoma (HCC) patients parallel to a reduced expression level of insulin-like growth factor (IGF)-1 in NK cells of HCC patients has been revealed. Ectopic expression of miR-486-5p, a direct upstream regulator of IGF-1, restored the endogenous level of IGF-1 in NK cells of HCC patients, thus augmenting its cytolytic activity against Huh7 cells in an opposite manner to the IGF-1 siRNAs. Unorthodoxly, over-expression of miR-486-5p in target hepatocytes resulted in the repression of IGF-1, suppression of Huh7 cells proliferation and viability in a similar pattern to the IGF-1 siRNAs. Therefore, this study highlights a potential role of IGF-1 in modulating cytolytic potential of NK cells of HCC patients. miR-486-5p acts in a cell-specific manner, differentially modulating IGF-1 expression in NK cells and their target hepatocytes with a contemporary inhibitory impact on HCC progression.

  7. Co-expression of Dsb proteins enables soluble expression of a single-chain variable fragment (scFv) against human type 1 insulin-like growth factor receptor (IGF-1R) in E. coli.

    Science.gov (United States)

    Sun, Xue-Wen; Wang, Xiao-Hua; Yao, Yan-Bing

    2014-12-01

    Type 1 insulin-like growth factor receptor (IGF-1R) is a promising therapeutic target for cancer treatment. A single-chain variable fragment (scFv) against human IGF-1R forms inclusion body when expressed in periplasmic space of E. coli routinely. Here, we described that co-expression of appropriate disulfide bonds (Dsb) proteins known to catalyze the formation and isomerization of Dsb can markedly recover the soluble expression of target scFv in E. coli. A 50 % recovery in solubility of the scFv was observed upon co-expression of DsbC alone, and a maximum solubility (80 %) was obtained when DsbA and DsbC were co-expressed in combination. Furthermore, the soluble scFv present full antigen-binding activity with IGF-1R, suggesting its correct folding. This study also suggested that the selection of Dsb proteins should be tested case-by-case if the approach of co-expression of Dsb system is adopted to address the problem of insoluble expression of proteins carrying Dsb.

  8. DNMT3A R882 Mutation with FLT3-ITD Positivity Is an Extremely Poor Prognostic Factor in Patients with Normal-Karyotype Acute Myeloid Leukemia after Allogeneic Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Ahn, Jae-Sook; Kim, Hyeoung-Joon; Kim, Yeo-Kyeoung; Lee, Seun-Shin; Jung, Sung-Hoon; Yang, Deok-Hwan; Lee, Je-Jung; Kim, Nan Young; Choi, Seung Hyun; Jung, Chul Won; Jang, Jun-Ho; Kim, Hee Je; Moon, Joon Ho; Sohn, Sang Kyun; Won, Jong-Ho; Kim, Sung-Hyun; Kim, Dennis Dong Hwan

    2016-01-01

    The prognostic relevance of epigenetic modifying genes (DNMT3A, TET2, and IDH1/2) in patients with acute myeloid leukemia (AML) has been investigated extensively. However, the prognostic implications of these mutations after allogeneic hematopoietic cell transplantation (HCT) have not been evaluated comprehensively in patients with normal-karyotype (NK)-AML. A total of 115 patients who received allogeneic HCT for NK-AML were retrospectively evaluated for the FLT3-ITD, NPM1, CEBPA, DNMT3A, TET2, IDH1/2, WT1, NRAS, ASXL2, FAT1, DNAH11, and GATA2 mutations in diagnostic samples and analyzed for long-term outcomes after allogeneic HCT. The prevalence rates for the mutations were as follows: FLT3-ITD positivity (FLT3-ITD(pos)) (32.2%), NPM1 mutation (43.5%), CEBPA mutation (double) (24.6%), DNMT3A mutation (DNMT3A(mut)) (31.3%), DNMT3A R882(mut) (18.3%), TET2 mutation (8.7%), and IDH1/2 mutation (16.5%). The 5-year overall survival (OS) and event-free survival (EFS) rates were 57.3% and 58.1%, respectively. A multivariate analysis revealed that FLT3-ITD(pos) (hazard ratio, [HR], 2.23; P = .006) and DNMT3A R882(mut) (HR, 2.74; P = .002) were unfavorable prognostic factors for OS. In addition, both mutations were significant risk factors for EFS and relapse. People with DNMT3A R882(mut) accompanied by FLT3-ITD(pos) had worse OS and EFS, and higher relapse rates than those with the other mutations, which were confirmed in a propensity score 1:2 matching analysis. These results suggest that DNMT3A R882(mut), particularly when accompanied by FLT3-ITD(pos), is a significant prognostic factor for inferior transplantation survival outcome by increasing relapse risk, even after allogeneic HCT.

  9. Histologic and Phenotypic Factors and MC1R Status Associated with BRAF(V600E), BRAF(V600K), and NRAS Mutations in a Community-Based Sample of 414 Cutaneous Melanomas.

    Science.gov (United States)

    Hacker, Elke; Olsen, Catherine M; Kvaskoff, Marina; Pandeya, Nirmala; Yeo, Abrey; Green, Adèle C; Williamson, Richard M; Triscott, Joe; Wood, Dominic; Mortimore, Rohan; Hayward, Nicholas K; Whiteman, David C

    2016-04-01

    Cutaneous melanomas arise through causal pathways involving interplay between exposure to UV radiation and host factors, resulting in characteristic patterns of driver mutations in BRAF, NRAS, and other genes. To gain clearer insights into the factors contributing to somatic mutation genotypes in melanoma, we collected clinical and epidemiologic data, performed skin examinations, and collected saliva and tumor samples from a community-based series of 414 patients aged 18 to 79, newly diagnosed with cutaneous melanoma. We assessed constitutional DNA for nine common polymorphisms in melanocortin-1 receptor gene (MC1R). Tumor DNA was assessed for somatic mutations in 25 different genes. We observed mutually exclusive mutations in BRAF(V600E) (26%), BRAF(V600K) (8%), BRAF(other) (5%), and NRAS (9%). Compared to patients with BRAF wild-type melanomas, those with BRAF(V600E) mutants were significantly younger, had more nevi but fewer actinic keratoses, were more likely to report a family history of melanoma, and had tumors that were more likely to harbor neval remnants. BRAF(V600K) mutations were also associated with high nevus counts. Both BRAF(V600K) and NRAS mutants were associated with older age but not with high sun exposure. We also found no association between MC1R status and any somatic mutations in this community sample of cutaneous melanomas, contrary to earlier reports.

  10. Effects of escitalopram, R-citalopram, and reboxetine on serum levels of tumor necrosis factor-α, interleukin-10, and depression-like behavior in mice after lipopolysaccharide administration.

    Science.gov (United States)

    Dong, Chao; Zhang, Ji-chun; Yao, Wei; Ren, Qian; Yang, Chun; Ma, Min; Han, Mei; Saito, Ryo; Hashimoto, Kenji

    2016-05-01

    Inflammation plays a role in the pathophysiology of depression. The purpose of this study is to examine whether the selective serotonin reuptake inhibitor (SSRI) escitalopram, its inactive enantiomer R-citalopram, and selective noradrenaline reuptake inhibitor (NRI) reboxetine, show anti-inflammatory and antidepressant effects in an inflammation-induced model of depression. Pretreatment with escitalopram (1, 3, or 10mg/kg, i.p.) markedly blocked an increase in the serum levels of pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α), after a single administration of lipopolysaccharide (LPS; 0.5mg/kg). Furthermore, escitalopram (3 or 10mg/kg) significantly increased the serum levels of the anti-inflammatory cytokine interleukin-10 (IL-10) by a single administration of LPS. In contrast, pretreatment with R-citalopram (10mg/kg, i.p.) or reboxetine (10mg/kg, i.p.) did not affect the alterations in serum levels of TNF-α and IL-10 after LPS administration. Co-administration of reboxetine with escitalopram did not show anti-inflammatory effects. Pretreatment with escitalopram (10mg/kg) significantly attenuated LPS-induced increase of the immobility time in the tail-suspension test (TST) and forced swimming test (FST). In contrast, pretreatment with R-citalopram (10mg/kg), or reboxetine (10mg/kg) did not alter LPS-induced increase of immobility time of TST and FST. Interestingly, co-administration of reboxetine with escitalopram did not show antidepressant effect in this model. These findings suggest that escitalopram, but not R-citalopram and reboxetine, has anti-inflammatory and antidepressant effects in LPS-treated model of depression, and that reboxetine can antagonize the effects of escitalopram in the inflammation model. Therefore, it is likely that serotonergic system plays a key role in the pathophysiology of inflammation-induced depression.

  11. Leadership In R

    Directory of Open Access Journals (Sweden)

    Mukan Nataliya

    2015-06-01

    Full Text Available In the article, leadership in R&D activity in English and Welsh universities has been studied. The main objectives of the article are defined as following: to analyze the scientific literature which highlights different aspects of the problem under research, to identify the specificity of leadership practice in R&D, and to develop the recommendations for leadership development in Ukrainian universities. Leadership in higher education has been studied by foreign and domestic scientists, especially, methodology of comparative education (C. Bargh, N. Bidyuk, N. Mukan, A. Sbruyeva; continuous professional education (J. Barge, A. Kuzminskyy, P. Lorange, N. Nychkalo; leadership in education (J. Bareham, L. Danylenko, L. Karamushka, N. Kolominskyy, O. Marmaza; leaders’ training (A. Borysova, V. Hromovyy etc. In Ukraine the problem of leadership in R&D has not been studied yet. The methodology of our research comprises theoretical (comparative and historical method, logical method, analysis and synthesis, and applied (conversations and dialogues methods. The research results have been presented: the fundamentals of leadership in R&D and its specificity in England and Wales; the factors of leadership in R&D of English and Welsh universities; the recommendations for leadership development in Ukrainian universities.

  12. Study of human factors, and its basic aspects focusing the IEA-R1 research reactor operators, aiming at the prevention of accidents caused by human failures; Estudo de fatores humanos e observacao dos seus aspectos basicos, focados em operadores do reator de pesquisa IEA-R1, objetivando a prevencao de acidentes ocasionados por falhas humanas

    Energy Technology Data Exchange (ETDEWEB)

    Martins, Maria da Penha Sanches

    2008-07-01

    This work presents a study of human factors and possible human failure reasons that can cause incidents, accidents and workers exposition, associated to risks intrinsic to the profession. The objective is to contribute with the operators of IEA-R1 reactor located at IPEN CNEN/S P. Accidents in the technological field, including the nuclear, have shown that the causes are much more connected to human failure than to system and equipment failures, what has led the regulatory bodies to consider studies on human failure. The research proposed in this work is quantitative/qualitative and also descriptive. Two questionnaires were used to collect data. The first of them was elaborated from the safety culture attributes which are described by the International Atomic Energy Agency - IAEA. The second considered individual and situational factors composing categories that could affect people in the work area. A carefully selected transcription of the theoretical basis according to the study of human factors was used. The methodology demonstrated a good reliability degree. Results lead to mediate factors which need direct actions concerning the needs of the group and of the individual. This research shows that it is necessary to have a really effective unit of planning and organization, not only to the physical and psychological health issues but also to the safety in the work. (author)

  13. SOCIO - DEMOGRAPHIC FACTORS AND PREVALENCE OF UNMET NEED FOR FAMILY PLANNING IN URBAN AND RURAL FIELD PRACTICE AREAS OF M . R . MEDICAL COLLEGE , KALABURAGI

    Directory of Open Access Journals (Sweden)

    Mohammad Waseem Faraz

    2015-08-01

    Full Text Available Millions of women in developing countries would prefer to avoid a pregnancy by not using any form of contraception. Hence unmet need can be powerful concept for family planning programmes. Today, more than 220 million women in developing countries report having an unmet need for family planning at different stages of their reproductive lives. “Unmet need can be powerful concept for family planning programmes. First, it is based on women’s own statements, an answer to survey question. Second, it identifies the group most likely to be interested in contraception. Third, it poses a clear challenge to reach and serve these women”. OBJECTIVES : 1 To assess the magnitude of Unmet need for family planning among married women of reproductive age group (15 – 44 years. 2 To identify the socio - demographic factors associated with unmet need for family planning. MATERIALS AND METHODS : A cross - sectional study was carried out in the Urban and Rural health training Centers of Department of Community Medicine. The study population included 563 married women from rural and 924 married women from urban area aged 15 - 44 years. The data was collected using pre tested proforma and was analyzed using percentages and Chi - Square test. RESULTS : The unmet need for family planning was 28.9% in urban and 40.5% in rural study populations. The overall unmet need is low at the beginning of reproductive age, but it increased and reached a peak in the mid - twenties & then declined. CONCLUSION : Despite a fair knowledge about the family planning methods, various socio - cultural and problems were responsible for the gap between a woman’s expressed need and utilization of contraceptives. Addressing these problems and barriers would help in the long run to reduce the unmet need. KEYWORDS : Unmet needs; Contraception; Spacing; Limiting.

  14. Human CD34+ CD133+ hematopoietic stem cells cultured with growth factors including Angptl5 efficiently engraft adult NOD-SCID Il2rγ-/- (NSG mice.

    Directory of Open Access Journals (Sweden)

    Adam C Drake

    Full Text Available Increasing demand for human hematopoietic stem cells (HSCs in clinical and research applications necessitates expansion of HSCs in vitro. Before these cells can be used they must be carefully evaluated to assess their stem cell activity. Here, we expanded cord blood CD34(+ CD133(+ cells in a defined medium containing angiopoietin like 5 and insulin-like growth factor binding protein 2 and evaluated the cells for stem cell activity in NOD-SCID Il2rg(-/- (NSG mice by multi-lineage engraftment, long term reconstitution, limiting dilution and serial reconstitution. The phenotype of expanded cells was characterized by flow cytometry during the course of expansion and following engraftment in mice. We show that the SCID repopulating activity resides in the CD34(+ CD133(+ fraction of expanded cells and that CD34(+ CD133(+ cell number correlates with SCID repopulating activity before and after culture. The expanded cells mediate long-term hematopoiesis and serial reconstitution in NSG mice. Furthermore, they efficiently reconstitute not only neonate but also adult NSG recipients, generating human blood cell populations similar to those reported in mice reconstituted with uncultured human HSCs. These findings suggest an expansion of long term HSCs in our culture and show that expression of CD34 and CD133 serves as a marker for HSC activity in human cord blood cell cultures. The ability to expand human HSCs in vitro should facilitate clinical use of HSCs and large-scale construction of humanized mice from the same donor for research applications.

  15. Factors that contribute to social media influence within an Internal Medicine Twitter learning community [v1; ref status: indexed, http://f1000r.es/3jd

    Directory of Open Access Journals (Sweden)

    Tejas Desai

    2014-05-01

    Full Text Available Medical societies, faculty, and trainees use Twitter to learn from and educate other social media users. These social media communities bring together individuals with various levels of experience. It is not known if experienced individuals are also the most influential members. We hypothesize that participants with the greatest experience would be the most influential members of a Twitter community. We analyzed the 2013 Association of Program Directors in Internal Medicine Twitter community. We measured the number of tweets authored by each participant and the number of amplified tweets (re-tweets. We developed a multivariate linear regression model to identify any relationship to social media influence, measured by the PageRank. Faculty (from academic institutions comprised 19% of the 132 participants in the learning community (p < 0.0001. Faculty authored 49% of all 867 tweets (p < 0.0001. Their tweets were the most likely to be amplified (52%, p < 0.01. Faculty had the greatest influence amongst all participants (mean 1.99, p < 0.0001. Being a faculty member had no predictive effect on influence (β = 0.068, p = 0.6. The only factors that predicted influence (higher PageRank were the number of tweets authored (p < 0.0001 and number of tweets amplified (p < 0.0001 The status of “faculty member” did not confer a greater influence. Any participant who was able to author the greatest number of tweets or have more of his/her tweets amplified could wield a greater influence on the participants, regardless of his/her authority.

  16. FGF growth factor analogs

    Science.gov (United States)

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

    2012-07-24

    The present invention provides a fibroblast growth factor heparin-binding analog of the formula: ##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y and Z are as defined, pharmaceutical compositions, coating compositions and medical devices including the fibroblast growth factor heparin-binding analog of the foregoing formula, and methods and uses thereof.

  17. Prevalence and risk factors of intestinal protozoan and helminth infections among pulmonary tuberculosis patients without HIV infection in a rural county in P. R. China.

    Science.gov (United States)

    Li, Xin-Xu; Chen, Jia-Xu; Wang, Li-Xia; Tian, Li-Guang; Zhang, Yu-Ping; Dong, Shuang-Pin; Hu, Xue-Guang; Liu, Jian; Wang, Feng-Feng; Wang, Yue; Yin, Xiao-Mei; He, Li-Jun; Yan, Qiu-Ye; Zhang, Hong-Wei; Xu, Bian-Li; Zhou, Xiao-Nong

    2015-09-01

    Although co-infection of tuberculosis (TB) and intestinal parasites, including protozoa and helminths, in humans has been widely studied globally, very little of this phenomenon is known in China. Therefore, a cross-sectional study was conducted in a rural county of China to investigate such co-infections. Patients with pulmonary TB (PTB) undergoing anti-Mycobacterium tuberculosis (anti-MTB) treatment were surveyed by questionnaires, and their feces and blood specimens were collected for detection of intestinal protozoa and helminths, routine blood examination and HIV detection. The χ(2) test and multivariate logistic regression model were used to identify risk factors. A total of 369 patients with PTB were included and all of them were HIV negative. Overall, only 7.3% of participants were infected with intestinal protozoa, among which prevalence of Blastocystis hominis, Entamoeba spp. and Trichomonas hominis were 6.0%, 1.1% and 0.3%, respectively; 7.0% were infected with intestinal helminths, among which prevalence of hookworm, Trichuris trichiura, Ascaris lumbricoides and Clonorchis sinensis were 4.3%, 1.9%, 0.5% and 0.3%, respectively; and 0.5% were simultaneously infected with intestinal protozoa and helminths. Among patients with PTB, body mass index (BMI)≤18 (OR=3.30, 95% CI=1.44-7.54) and raised poultry or livestock (e.g., chicken, duck, pig) (OR=3.96, 95% CI=1.32-11.89) were significantly associated with harboring intestinal protozoan infection, while BMI≤18 (OR=3.32, 95% CI=1.39-7.91), anemia (OR=3.40, 95% CI=1.44-8.02) and laboring barefoot in farmlands (OR=4.54, 95% CI=1.88-10.92) were significantly associated with having intestinal helminth infection. Additionally, there was no significant relationship between duration of anti-MTB treatment and infection rates of intestinal parasites including protozoa and helminths. Therefore, preventing malnutrition, avoiding unprotected contact with reservoirs of protozoa, and improving health education for good

  18. System performance with R407A, R407B, R407C compared to R22

    DEFF Research Database (Denmark)

    Knudsen, Hans Jørgen Høgaard

    1997-01-01

    The article presents the results obtained by substituting R22 with mixture of R32/R125/R134A (R407A, R407B and R407C) in an existing refrigeration plant. Cooling capacity, coefficient of performance and heat transfer coefficient in the evaporator have been measured.The results show that for R407C...

  19. Insulin-like growth factor-binding protein-3 (IGFBP-3) blocks the effects of asthma by negatively regulating NF-κB signaling through IGFBP-3R-mediated activation of caspases.

    Science.gov (United States)

    Lee, Yong-Chul; Jogie-Brahim, Sherryline; Lee, Dae-Yeol; Han, Jinfeng; Harada, Aki; Murphy, Liam J; Oh, Youngman

    2011-05-20

    Insulin-like growth factor-binding protein-3 (IGFBP-3) is a multifunctional protein known for modulating mitogenic and metabolic actions of IGFs as well as exerting a variety of biological actions not involving IGFs. Here, we show that IGFBP-3 blocks specific physiological consequences of asthma in an IGF-independent manner in vitro and in vivo. IGFBP-3 treatment effectively reduced all physiological manifestations of asthma examined in vivo (airway hyper-responsiveness, cellular and pathological changes in bronchoalveolar lavage fluid and lung tissue, and expression of numerous proinflammatory molecules). These unique IGFBP-3 effects were further confirmed in IGFBP-3-transgenic mice, thus strengthening the notion of IGFBP-3 actions within the respiratory system. Using human epithelial cells, we demonstrated the following: 1) IGFBP-3 blocks TNF-α-induced expression of proinflammatory molecules; 2) IGFBP-3 attenuates the TNF-α-induced migratory response of eosinophils; and 3) IGFBP-3 negatively regulates TNF-α-induced expression of the key NF-κB regulatory molecules IκBα and p65-NF-κB at the post-translational level. We identified that IGFBP-3 degrades IκBα and p65-NF-κB proteins through IGFBP-3 receptor (IGFBP-3R)-mediated activation of caspases thereby inhibiting TNF-α-induced activation of NF-κB signaling cascades. This unique IGFBP-3/IGFBP-3R action was further confirmed by demonstrating complete inhibition of IGFBP-3 action in the presence of caspase inhibitors as well as IGFBP-3R siRNAs. Non-IGF-binding IGFBP-3 mutants further proved the IGF-independent action of IGFBP-3. Our findings indicate that IGFBP-3 inhibits airway inflammation and hyper-responsiveness via an IGF-independent mechanism that involves activation of IGFBP-3R signaling and cross-talk with NF-κB signaling. The IGFBP-3/IGFBP-3R system therefore plays a pivotal role in the pathogenesis of asthma and can serve as a newly identified potential therapeutic target for this debilitating

  20. Calculation for Franck-Condon Factors of the Two Band Systems β(B2Π r-X2Πr) and γ(A2Σ+-X2Πr) of NO in the Air at High Temperature%高温空气中NO分子β(B2Πr-X2Πr)及γ(A2Σ+-X2Πr) 发光带系的Franck-Condon因子计算

    Institute of Scientific and Technical Information of China (English)

    张中明; 普小云; 林理忠; 熊烨

    1999-01-01

    在双原子分子核运动的波动方程中,计入分子的振转相互作用项,得出的波函数除与振动量子数有关外,还与转动量子数有关.本文用该波函数编程计算了高温空气中NO分子β(B2Πr-X2Πr)及γ(A2Σ+-X2Πr)带系的Franck-Condon因子.计算中转动量子数的取值由J=0取至J=200,结果适用于低温和高温条件.

  1. 跨国公司与中国高校 R & D 合作中技术溢出影响因素的实证研究%Empirical Research on Influence Factors of Technology Spillovers in the R & D Cooperation between MNCs and Colleges and Universities in China

    Institute of Scientific and Technical Information of China (English)

    张宏伟; 崔新健

    2013-01-01

    Empirical Research on influence factors of technology spillovers in the R&D cooperation between MNCs and colleges&u-niversities in China plays an important role in strengthening R&D cooperation ,promoting technology spillovers from MNCs to Chinese col-leges&universities ,and improving Chinese national innovation system .Based on the investigation and the existing theory literature , the paper puts forward hypothesis ,carries out hypothesis testing through questionnaires statistical analysis ,and demonstrates the influence fac-tors of technology spillovers in R&D cooperation between MNCs and colleges&universities .The results suggest that :the relation between managerial communication level and cooperation environment and scientific research capacity benefits from Chinese colleges&universities , status gap in R&D cooperation and scientific research management benefits , and technology gap and research resource benefits is negative , but technology gap between MNCs and colleges&universities exerts an positive influence on education function benefits .%探究跨国公司和中国高校R&D合作中技术溢出的影响因素,对于增强R&D合作,促进跨国公司向我国高校的技术溢出以及完善国家创新体系具有重要价值。在现有理论文献和调查的基础上,提出假设,通过问卷统计分析对跨国公司与中国高校R&D合作中技术溢出的影响因素进行了实证检验,研究结果表明,现有沟通交流水平以及合作环境状况对高校科研能力获益,高校与跨国公司的合作地位差距对高校科研管理获益,以及高校与跨国公司的技术差距对高校科研资源获益均产生负面影响,但高校与跨国公司的技术差距却对高校教育功能获益产生正向影响。

  2. Measurement of charged particle spectra in pp collisions and nuclear modification factor $R_\\mathrm{pPb}$ at $\\sqrt{s_{NN}}=5.02$TeV with the ATLAS detector at the LHC

    CERN Document Server

    The ATLAS collaboration

    2016-01-01

    This note presents an analysis of the inclusive charged particle spectra in pp collisions at $\\sqrt{s}=5.02$TeV that are measured with the ATLAS experiment at the LHC. The measurements are performed with pp data recorded in 2015 with an integrated luminosity of 25pb$^{-1}$. The ratio of spectra measured in the p+Pb collisions to the pp cross section scaled by the number of binary nucleon-nucleon collisions, $R_\\mathrm{pPb}$, is evaluated to facilitate a comparison of the particle production in the two colliding systems. The nuclear modification factor does not show any significant deviation from unity in the probed transverse momentum region.

  3. Measurement of nuclear modification factor $R_{\\rm{AA}}$ in Pb+Pb collisions at $\\sqrt{s_{_{\\rm{NN}}}}=5.02TeV$ with the ATLAS detector at the LHC

    CERN Document Server

    Milov, Alexander; The ATLAS collaboration

    2017-01-01

    This poster presents inclusive charged hadron spectra measured in Pb+Pb collisions at $\\sqrt{s_{_{\\rm{NN}}}}=5.02$TeV with the ATLAS detector at the LHC. The measurements are performed with data recorded in 2015 with the integrated luminosity of 0.49nb$^{−1}$. Spectra measured in centrality intervals is compared to the pp data with integrated luminosity of 25pb$^{−1}$ obtained the same year to form the nuclear modification factor, RAA. Its behavior is studied as a function of the systems size and as a function of the hadron transverse momentum, pT, up to 300GeV. The $R_{\\rm{AA}}$ measured at $\\sqrt{s_{_{\\rm{NN}}}}=5.02$TeV in general is found to be consistent with the previous measurement published by the ATLAS experiment. Above 60GeV, $R_{\\rm{AA}}$ is consistent with a plateau at a centrality-dependent value, within the uncertainties.

  4. Routine Primary Prophylaxis for Febrile Neutropenia with Biosimilar Granulocyte Colony-Stimulating Factor (Nivestim or Pegfilgrastim Is Cost Effective in Non-Hodgkin Lymphoma Patients undergoing Curative-Intent R-CHOP Chemotherapy.

    Directory of Open Access Journals (Sweden)

    Xiao Jun Wang

    Full Text Available This study aims to compare the cost-effectiveness of various strategies of myeloid growth factor prophylaxis for reducing the risk of febrile neutropenia (FN in patients with non-Hodgkin lymphoma in Singapore who are undergoing R-CHOP chemotherapy with curative intent.A Markov model was created to compare seven prophylaxis strategies: 1 primary prophylaxis (PP with nivestim (biosimilar filgrastim throughout all cycles of chemotherapy; 2 PP with nivestim during the first two cycles of chemotherapy; 3 secondary prophylaxis (SP with nivestim; 4 PP with pegfilgrastim throughout all cycles of chemotherapy; 5 PP with pegfilgrastim during the first two cycles of chemotherapy; 6 SP with pegfilgrastim; and 7 no prophylaxis (NP. The perspective of a hospital was taken and cost-effectiveness was expressed as the cost per episode of FN avoided over six cycles of chemotherapy. A probabilistic sensitivity analysis was conducted.Strategies 3, 6, and 7 were dominated in the base case analysis by strategy 5. The costs associated with strategies 2, 5, 1, and 4 were US$3,813, US$4,056, US$4,545, and US$5,331, respectively. The incremental cost-effectiveness ratios for strategy 5 vs. strategy 2, strategy 1 vs. strategy 5, and strategy 4 vs. strategy 1 were US$13,532, US$22,565, and US$30,452, respectively, per episode of FN avoided. Strategy 2 has the highest probability to be cost-effective (ranged from 48% to 60% when the willingness to pay (WTP threshold is lower than US$10,000 per FN episode prevented.In Singapore, routine PP with granulocyte colony-stimulating factor (nivestim or pegfilgrastim is cost-effective for reducing the risk of FN in patients receiving R-CHOP.

  5. A erosividade das chuvas em Fortaleza (CE: II - correlação com o coeficiente de chuva e atualização do fator R no período de 1962 a 2000 Rainfall erosivity in Fortaleza, Ceará State, Brazil: II - correlation with the rainfall coefficient and updating of factor R for the years 1962 to 2000

    Directory of Open Access Journals (Sweden)

    J. R. C. Silva

    2003-04-01

    Full Text Available A correlação entre o índice de erosividade EI30 e o coeficiente de chuva (Rc no período de 1962 a 1981, em Fortaleza (CE, foi avaliada com o objetivo não só de analisar a viabilidade de utilização do Rc na atualização dos valores da erosividade no período de 1982 a 2000 nesse município, mas também de identificar uma equação que pudesse ser empregada para estimar a erosividade em outras localidades da zona litorânea do estado do Ceará onde não existem diagramas de pluviógrafos. Um alto coeficiente de correlação (r = 0,99** foi encontrado entre os valores mensais do índice EI30 e o Rc. O melhor ajuste na regressão entre essas variáveis foi encontrado na equação EI30 = 73,989Rc0,7387. O emprego dessa equação permitiu atualizar o fator R em Fortaleza no período de 1962 a 2000, estendendo, dessa forma, a computação de dados de erosividade para uma série contínua de 39 anos. O fator R atualizado para essa série foi de 6.900 MJ mm (ha h ano-1 , com 69,5 % desse valor anual distribuído nos meses de janeiro a abril. Este trabalho também forneceu informações úteis para planejar o controle da erosão e para estimar, com precisão razoável, a erosividade em outros locais do litoral cearense, desprovidos de diagramas de pluviógrafos.The correlation between the erosivity index EI30 and the rainfall coefficient (Rc for the period of 1962 to 1981, in Fortaleza (CE, was evaluated to analyze the feasibility of the Rc use to update erosivity values from 1982 to 2000 in this county. An equation that could be used to estimate erosivity in other locations of the coastal region of Ceará State, where there are no rain gauge charts available, was a second aim. A high correlation coefficient (r = 0,99** was found between the monthly EI30 index and the Rc values. The best fit in the regression between these variables was found in the equation EI30 = 73,989Rc0,7387. The use of this equation allowed to update the R factor in

  6. Upper bound for R(a,l)

    CERN Document Server

    Rumyantsev, Andrey

    2010-01-01

    Let $A$ be an $a$-letter alphabet. We consider fractional powers of $A$-strings: if $x$ is a $n$-letter string, $x^r$ is a prefix of $xxxx\\...$ having length $nr$. Let $l$ be a positive integer. Ilie, Ochem and Shallit defined $R(a,l)$ as the infimum of reals $r>1$ such that there exist a sequence $\\omega$ (of $A$-letters) without factors $y$ that are fractional powers $x^{r'}$ where $x$ has length at least $l$ and $r'\\ge r$. We prove that $1+\\frac{1}{la}\\le R(a,l)\\le 1+\\frac{c}{la}$ for some constant $c$.

  7. Some variables predicting five factor personality of adolescentsErgenlerin beş faktör kişilik özelliğini yordayan bazı değişkenler

    Directory of Open Access Journals (Sweden)

    Mehmet Bilgin

    2016-09-01

    Full Text Available In this study, variables predicting the five-factor personality traits of adolescents were examined. These variables are cognitive flexibility, social self-efficacy, and cognitive errors. Research on middle and high school students from 7th.8th.9th.10th.11th.and 12th grades, a total of 441 students, participated to the study. In the study, the Five Factor Personality Inventory, Social Self Efficacy Scale, Cognitive Flexibility Scale and Cognitive Errors Questionnaire were used. The findings of the study show that significant predictied variables for five personality traits are cognitive flexibility, social self-efficacy and cognitive errors. As a result, positive relationship between social self-efficacy and extraversion, aggreeablesness, and openness to experiences personality traits were emerged. It was determined that there was a positive relationship between self-control personality traits and cognitive flexibility, and a negative relationship cognitive flexibility with neuroticism. However, results showed that over-generalization error was commonly used by people who had self-control and neuroticism personality traits. Self-control and agreeablesness of the personality traits were used at the same time personalization errors.  It is determined that only individuals with agreeablesness trait seemed to made error of selective abstraction. Overall, It is seen that people who are cognitive flexibility are extraversion, agreeablesness, self-control and openness to experiences personality traits.    Özet Bu çalışmada, ergenlerin beş faktör kişilik özelliklerini yordayan değişkenler incelenmeye çalışılmıştır.  Bu değişkenler bilişsel esneklik, sosyal yetkinlik ve bilişsel hatalardır. Araştırmaya 7.8.9.10.11.ve 12 sınıf öğrencileri olmak üzere toplam 441 öğrenci katılmıştır. Araştırmada beş faktör kişilik envanteri, bilişsel esneklik ölçeği, bilişsel hatalar ölçeği ve sosyal yetkinlik beklentisi

  8. Intestinal DMBT1 expression is modulated by Crohn's disease-associated IL23R variants and by a DMBT1 variant which influences binding of the transcription factors CREB1 and ATF-2.

    Directory of Open Access Journals (Sweden)

    Julia Diegelmann

    Full Text Available OBJECTIVES: DMBT is an antibacterial pattern recognition and scavenger receptor. In this study, we analyzed the role of DMBT1 single nucleotide polymorphisms (SNPs regarding inflammatory bowel disease (IBD susceptibility and examined their functional impact on transcription factor binding and downstream gene expression. METHODS: Seven SNPs in the DMBT1 gene region were analyzed in 2073 individuals including 818 Crohn's disease (CD patients and 972 healthy controls in two independent case-control panels. Comprehensive epistasis analyses for the known CD susceptibility genes NOD2, IL23R and IL27 were performed. The influence of IL23R variants on DMBT1 expression was analyzed. Functional analysis included siRNA transfection, quantitative PCR, western blot, electrophoretic mobility shift and luciferase assays. RESULTS: IL-22 induces DMBT1 protein expression in intestinal epithelial cells dependent on STAT3, ATF-2 and CREB1. IL-22 expression-modulating, CD risk-associated IL23R variants influence DMBT1 expression in CD patients and DMBT1 levels are increased in the inflamed intestinal mucosa of CD patients. Several DMBT1 SNPs were associated with CD susceptibility. SNP rs2981804 was most strongly associated with CD in the combined panel (p = 3.0 × 10(-7, OR 1.42; 95% CI 1.24-1.63. All haplotype groups tested showed highly significant associations with CD (including omnibus P-values as low as 6.1 × 10(-18. The most strongly CD risk-associated, non-coding DMBT1 SNP rs2981804 modifies the DNA binding sites for the transcription factors CREB1 and ATF-2 and the respective genomic region comprising rs2981804 is able to act as a transcriptional regulator in vitro. Intestinal DMBT1 expression is decreased in CD patients carrying the rs2981804 CD risk allele. CONCLUSION: We identified novel associations of DMBT1 variants with CD susceptibility and discovered a novel functional role of rs2981804 in regulating DMBT1 expression. Our data suggest an important

  9. Intestinal DMBT1 expression is modulated by Crohn's disease-associated IL23R variants and by a DMBT1 variant which influences binding of the transcription factors CREB1 and ATF-2.

    Science.gov (United States)

    Diegelmann, Julia; Czamara, Darina; Le Bras, Emmanuelle; Zimmermann, Eva; Olszak, Torsten; Bedynek, Andrea; Göke, Burkhard; Franke, Andre; Glas, Jürgen; Brand, Stephan

    2013-01-01

    DMBT is an antibacterial pattern recognition and scavenger receptor. In this study, we analyzed the role of DMBT1 single nucleotide polymorphisms (SNPs) regarding inflammatory bowel disease (IBD) susceptibility and examined their functional impact on transcription factor binding and downstream gene expression. Seven SNPs in the DMBT1 gene region were analyzed in 2073 individuals including 818 Crohn's disease (CD) patients and 972 healthy controls in two independent case-control panels. Comprehensive epistasis analyses for the known CD susceptibility genes NOD2, IL23R and IL27 were performed. The influence of IL23R variants on DMBT1 expression was analyzed. Functional analysis included siRNA transfection, quantitative PCR, western blot, electrophoretic mobility shift and luciferase assays. IL-22 induces DMBT1 protein expression in intestinal epithelial cells dependent on STAT3, ATF-2 and CREB1. IL-22 expression-modulating, CD risk-associated IL23R variants influence DMBT1 expression in CD patients and DMBT1 levels are increased in the inflamed intestinal mucosa of CD patients. Several DMBT1 SNPs were associated with CD susceptibility. SNP rs2981804 was most strongly associated with CD in the combined panel (p = 3.0 × 10(-7), OR 1.42; 95% CI 1.24-1.63). All haplotype groups tested showed highly significant associations with CD (including omnibus P-values as low as 6.1 × 10(-18)). The most strongly CD risk-associated, non-coding DMBT1 SNP rs2981804 modifies the DNA binding sites for the transcription factors CREB1 and ATF-2 and the respective genomic region comprising rs2981804 is able to act as a transcriptional regulator in vitro. Intestinal DMBT1 expression is decreased in CD patients carrying the rs2981804 CD risk allele. We identified novel associations of DMBT1 variants with CD susceptibility and discovered a novel functional role of rs2981804 in regulating DMBT1 expression. Our data suggest an important role of DMBT1 in CD pathogenesis.

  10. EARLY ENVIRONMENTAL FACTORS IN AUTISM. (R824758)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  11. R&D Jobs for BS Engineers.

    Science.gov (United States)

    Basta, Nicholas

    1985-01-01

    Outlines opportunities for beginning engineers seeking employment in research and development (R&D). R&D spending growth, underlying factors, job categories, and divisions within an industrial firm are discussed. Above average grades and additional mathematics courses are primary requirements for an R&D position, which may later lead to…

  12. Psychometric Properties of Spanish Version of the Three-Factor Eating Questionnaire-R18 (Tfeq-Sp and Its Relationship with Some Eating- and Body Image-Related Variables

    Directory of Open Access Journals (Sweden)

    Ignacio Jáuregui-Lobera

    2014-12-01

    Full Text Available The aims of this study were to analyze the psychometric properties of the Spanish version of the Three-Factor Eating Questionnaire-R18 (TFEQ-SP, as well as determine its validity by evaluating the relationship of the TFEQ-SP with different parameters related to body mass index, weight perception, perception of physical fitness, self-esteem, and food intake, as well as with weight control-related variables. A total of 281 participants (aged 18.38 ± 6.31 were studied. The factor analysis yielded three factors: cognitive restraint (CR, uncontrolled eating (UE, and emotional eating (EE. The internal consistency of the TFEQ-SP was determined by means of Cronbach’s α coefficient, with values ranging between 0.75 and 0.87. Higher scores on CR were found in women (p < 0.5, overweight/obese participants (p < 0.001, participants with lower self-esteem (p < 0.05, participants who overestimated their weight (p < 0.001, participants who weighed themselves frequently (p < 0.001 and those who were about to go on a diet (p < 0.001. Higher EE scores were found in participants with lower self-esteem scores (p < 0.05, among participants with a poorer perception of their physical fitness (p < 0.01 and when participants were about to diet (p < 0.05. Higher scores on UE were observed in case of poorer perception of physical fitness (p < 0.05. The validation study of the TFEQ-SP meets the requirements for measuring the three different facets of eating behavior: CR, UE, and EE.

  13. Psychometric Properties of Spanish Version of the Three-Factor Eating Questionnaire-R18 (Tfeq-Sp) and Its Relationship with Some Eating- and Body Image-Related Variables

    Science.gov (United States)

    Jáuregui-Lobera, Ignacio; García-Cruz, Patricia; Carbonero-Carreño, Rocío; Magallares, Alejandro; Ruiz-Prieto, Inmaculada

    2014-01-01

    The aims of this study were to analyze the psychometric properties of the Spanish version of the Three-Factor Eating Questionnaire-R18 (TFEQ-SP), as well as determine its validity by evaluating the relationship of the TFEQ-SP with different parameters related to body mass index, weight perception, perception of physical fitness, self-esteem, and food intake, as well as with weight control-related variables. A total of 281 participants (aged 18.38 ± 6.31) were studied. The factor analysis yielded three factors: cognitive restraint (CR), uncontrolled eating (UE), and emotional eating (EE). The internal consistency of the TFEQ-SP was determined by means of Cronbach’s α coefficient, with values ranging between 0.75 and 0.87. Higher scores on CR were found in women (p < 0.5), overweight/obese participants (p < 0.001), participants with lower self-esteem (p < 0.05), participants who overestimated their weight (p < 0.001), participants who weighed themselves frequently (p < 0.001) and those who were about to go on a diet (p < 0.001). Higher EE scores were found in participants with lower self-esteem scores (p < 0.05), among participants with a poorer perception of their physical fitness (p < 0.01) and when participants were about to diet (p < 0.05). Higher scores on UE were observed in case of poorer perception of physical fitness (p < 0.05). The validation study of the TFEQ-SP meets the requirements for measuring the three different facets of eating behavior: CR, UE, and EE. PMID:25486370

  14. Factor X assay

    Science.gov (United States)

    ... D, Neff AT. Rare coagulation factor deficiencies. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, ... Laboratory evaluation of hemostatic and thrombotic disorders. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, ...

  15. Factor XII assay

    Science.gov (United States)

    ... D, Neff AT. Rare coagulation factor deficiencies. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, ... Laboratory evaluation of hemostatic and thrombotic disorders. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, ...

  16. Retención de nitrógeno y procesos biogeoquímicos en ríos mediterráneos semiáridos : factores medioambientales implicados en su variación espacial y temporal= Nitrogen retention and biogeochemical processes in mediterranean semiarid streams : environmental factors involved in their spatial and temporal variation

    OpenAIRE

    Arce Sánchez, María Isabel

    2014-01-01

    En paisajes Mediterráneos semiáridos, las prácticas agrícolas, la escasez de agua y la salinidad natural de muchos suelos son, tanto directa como directamente, factores potenciales que pueden controlar la variación de la retención de nitrógeno (N) en ríos. De todos los procesos biogeoquímicos implicados en el ciclo del N, el proceso de desnitrificación es, en comparación, sumamente relevante ya que este proceso es el único capaz de eliminar N del ecosistema de forma permanente. Este proceso, ...

  17. The Phosphoinositide 3-Kinase p110α Isoform Regulates Leukemia Inhibitory Factor Receptor Expression via c-Myc and miR-125b to Promote Cell Proliferation in Medulloblastoma.

    Directory of Open Access Journals (Sweden)

    Fabiana Salm

    Full Text Available Medulloblastoma (MB is the most common malignant brain tumor in childhood and represents the main cause of cancer-related death in this age group. The phosphoinositide 3-kinase (PI3K pathway has been shown to play an important role in the regulation of medulloblastoma cell survival and proliferation, but the molecular mechanisms and downstream effectors underlying PI3K signaling still remain elusive. The impact of RNA interference (RNAi-mediated silencing of PI3K isoforms p110α and p110δ on global gene expression was investigated by DNA microarray analysis in medulloblastoma cell lines. A subset of genes with selectively altered expression upon p110α silencing in comparison to silencing of the closely related p110δ isoform was revealed. Among these genes, the leukemia inhibitory factor receptor α (LIFR α was validated as a novel p110α target in medulloblastoma. A network involving c-Myc and miR-125b was shown to be involved in the control of LIFRα expression downstream of p110α. Targeting the LIFRα by RNAi, or by using neutralizing reagents impaired medulloblastoma cell proliferation in vitro and induced a tumor volume reduction in vivo. An analysis of primary tumors revealed that LIFRα and p110α expression were elevated in the sonic hedgehog (SHH subgroup of medulloblastoma, indicating its clinical relevance. Together, these data reveal a novel molecular signaling network, in which PI3K isoform p110α controls the expression of LIFRα via c-Myc and miR-125b to promote MB cell proliferation.

  18. R/2R DAC Nonlinearity Compensation

    OpenAIRE

    Kulig, Gabriel; Wallin, Gustav

    2012-01-01

    The resistor ladder (R/2R) digital-to-analogue converter (DAC) architecture is often used in high performance audio solutions due to its low-noise performance. Even high-end R/2R DACs suffer from static nonlinearity distortions. It was suspected that compensating for these nonlinearities would be possible. It was also suspected that this could improve audio quality in audio systems using R/2R DACs for digital-to-analogue (A/D) conversion. Through the use of models of the resistor ladder archi...

  19. R quick syntax reference

    CERN Document Server

    Tollefson, Margot

    2014-01-01

    The R Quick Syntax Reference is a handy reference book detailing the intricacies of the R language. Not only is R a free, open-source tool, R is powerful, flexible, and has state of the art statistical techniques available. With the many details which must be correct when using any language, however, the R Quick Syntax Reference makes using R easier.Starting with the basic structure of R, the book takes you on a journey through the terminology used in R and the syntax required to make R work. You will find looking up the correct form for an expression quick and easy. With a copy of the R Quick

  20. Purification optimization for a recombinant single-chain variable fragment against type 1 insulin-like growth factor receptor (IGF-1R) by using design of experiment (DoE).

    Science.gov (United States)

    Song, Yong-Hong; Sun, Xue-Wen; Jiang, Bo; Liu, Ji-En; Su, Xian-Hui

    2015-12-01

    Design of experiment (DoE) is a statistics-based technique for experimental design that could overcome the shortcomings of traditional one-factor-at-a-time (OFAT) approach for protein purification optimization. In this study, a DoE approach was applied for optimizing purification of a recombinant single-chain variable fragment (scFv) against type 1 insulin-like growth factor receptor (IGF-1R) expressed in Escherichia coli. In first capture step using Capto L, a 2-level fractional factorial analysis and successively a central composite circumscribed (CCC) design were used to identify the optimal elution conditions. Two main effects, pH and trehalose, were identified, and high recovery (above 95%) and low aggregates ratio (below 10%) were achieved at the pH range from 2.9 to 3.0 with 32-35% (w/v) trehalose added. In the second step using cation exchange chromatography, an initial screening of media and elution pH and a following CCC design were performed, whereby the optimal selectivity of the scFv was obtained on Capto S at pH near 6.0, and the optimal conditions for fulfilling high DBC and purity were identified as pH range of 5.9-6.1 and loading conductivity range of 5-12.5 mS/cm. Upon a further gel filtration, the final purified scFv with a purity of 98% was obtained. Finally, the optimized conditions were verified by a 20-fold scale-up experiment. The purities and yields of intermediate and final products all fell within the regions predicted by DoE approach, suggesting the robustness of the optimized conditions. We proposed that the DoE approach described here is also applicable in production of other recombinant antibody constructs.

  1. 75 FR 68970 - Amendment of Using Agency for Restricted Areas R-4002, R-4005, R-4006 and R-4007; MD

    Science.gov (United States)

    2010-11-10

    ... Restricted Areas R-4002, R-4005, R- 4006 and R-4007; MD AGENCY: Federal Aviation Administration (FAA), DOT... restricted areas R-4002, Bloodsworth Island, MD; and R-4005, R-4006 and R-4007, Patuxent River, MD to ``U.S... areas R-4002, R-4005, R-4006 and R-4007 in Maryland, in order to reflect the correct......

  2. Determinación de factores de enriquecimiento y geoacumulación de Cd, Cr, Cu, Ni, Pb, y Zn en suelos de la cuenca alta del río Lerma

    Directory of Open Access Journals (Sweden)

    Pedro del Aguila Juárez

    2005-01-01

    Full Text Available Se determinó el índice degeoacumulación regional (Igeo y el factor deenriquecimiento (EF en suelos irrigados de lacuenca alta del río Lerma, Estado de México.Se colectaron 55 muestras de suelo de cincolocalidades: Tlachaloya, Ixtlahuaca,Atlacomulco, Temascalcingo y Amealco. Laspropiedades químicas analizadas fueron pH,capacidad de intercambio catiónico, arcilla,materia orgánica, concentración de Cr, Cu, Cd,Ni, Zn, y Pb; así como el Igeo y FE. Los suelosse consideraron excelentes para su usoagrícola en cuanto a los valores de pH ymateria orgánica (MO. Las concentraciones demetales pesados se encontraron por debajo delos límites permisibles. De acuerdo con elfactor de enriquecimiento, el Pb se considerócomo un contaminante moderado con unorigen tanto geológico como antropogénico.El índice de geocumulación mostró que el Pby el Ni son los mayores contaminantes del suelo.

  3. Ab initio based atomic scattering amplitudes and {l_brace}002{r_brace} electron structure factors of In{sub x}Ga{sub 1-x}As/GaAs quantum wells

    Energy Technology Data Exchange (ETDEWEB)

    Titantah, J T; Lamoen, D [EMAT, Universiteit Antwerpen, Groenenborgerlaan 171, 2020 Antwerpen (Belgium); Schowalter, M; Rosenauer, A, E-mail: john.titantah@ua.ac.b [Institut fuer Festkoerperphysik, Universitaet Bremen, D 28359 Bremen (Germany)

    2010-02-01

    The atomic scattering amplitudes of the various atoms of the systems Ga{sub 1-x}In{sub x}As, GaAs{sub 1-x}N{sub x} and InAs{sub 1-x}N{sub x} are calculated using the density functional theory (DFT) approach. The scattering amplitudes of N, Ga, As and In in the model systems are compared with the frequently used Doyle and Turner values. Deviation from the latter values is found for small scattering vectors (s<0.3A{sup -1}) and for these scattering vectors dependence on the orientation of the scattering vector and the chemical environment is reported. We suggest a parametrization of these modified scattering amplitudes (MASAs) for small scattering vectors (s<1.0A{sup -1}). The MASAs are exploited within zero pressure classical Metropolis Monte Carlo (MC), finite temperature calculations to investigate the effect of quantum well size on the electron {l_brace}002{r_brace} structure factor (SF) of Ga{sub 1-x}In{sub x}As quantum wells.

  4. Comparison of Body Mass Index (BMI), Body Adiposity Index (BAI), Waist Circumference (WC), Waist-To-Hip Ratio (WHR) and Waist-To-Height Ratio (WHtR) as predictors of cardiovascular disease risk factors in an adult population in Singapore.

    Science.gov (United States)

    Lam, Benjamin Chih Chiang; Koh, Gerald Choon Huat; Chen, Cynthia; Wong, Michael Tack Keong; Fallows, Stephen J

    2015-01-01

    Excess adiposity is associated with cardiovascular disease (CVD) risk factors such as hypertension, diabetes mellitus and dyslipidemia. Amongst the various measures of adiposity, the best one to help predict these risk factors remains contentious. A novel index of adiposity, the Body Adiposity Index (BAI) was proposed in 2011, and has not been extensively studied in all populations. Therefore, the purpose of this study is to compare the relationship between Body Mass Index (BMI), Waist Circumference (WC), Waist-to-Hip Ratio (WHR), Waist-to-Height Ratio (WHtR), Body Adiposity Index (BAI) and CVD risk factors in the local adult population. This is a cross sectional study involving 1,891 subjects (Chinese 59.1% Malay 22.2%, Indian 18.7%), aged 21-74 years, based on an employee health screening (2012) undertaken at a hospital in Singapore. Anthropometric indices and CVD risk factor variables were measured, and Spearman correlation, Receiver Operating Characteristic (ROC) curves and multiple logistic regressions were used. BAI consistently had the lower correlation, area under ROC and odd ratio values when compared with BMI, WC and WHtR, although differences were often small with overlapping 95% confidence intervals. After adjusting for BMI, BAI did not further increase the odds of CVD risk factors, unlike WC and WHtR (for all except hypertension and low high density lipoprotein cholesterol). When subjects with the various CVD risk factors were grouped according to established cut-offs, a BMI of ≥23.0 kg/m2 and/or WHtR ≥0.5 identified the highest proportion for all the CVD risk factors in both genders, even higher than a combination of BMI and WC. BAI may function as a measure of overall adiposity but it is unlikely to be better than BMI. A combination of BMI and WHtR could have the best clinical utility in identifying patients with CVD risk factors in an adult population in Singapore.

  5. Determination of scaling factors to estimate the radionuclide inventory in waste with low and intermediate-level activity from the IEA-R1 reactor; Determinacao de fatores de escala para estimativa do inventario de radionuclideos em rejeitos de media e baixa atividades do reator IEA-R1

    Energy Technology Data Exchange (ETDEWEB)

    Taddei, Maria Helena Tirollo

    2013-07-01

    Regulations regarding transfer and final disposal of radioactive waste require that the inventory of radionuclides for each container enclosing such waste must be estimated and declared. The regulatory limits are established as a function of the annual radiation doses that members of the public could be exposed to from the radioactive waste repository, which mainly depend on the activity concentration of radionuclides, given in Bq/g, found in each waste container. Most of the radionuclides that emit gamma-rays can have their activity concentrations determined straightforwardly by measurements carried out externally to the containers. However, radionuclides that emit exclusively alpha or beta particles, as well as gamma-rays or X-rays with low energy and low absolute emission intensity, or whose activity is very low among the radioactive waste, are generically designated as Difficult to Measure Nuclides (DTMs). The activity concentrations of these DTMs are determined by means of complex radiochemical procedures that involve isolating the chemical species being studied from the interference in the waste matrix. Moreover, samples must be collected from each container in order to perform the analyses inherent to the radiochemical procedures, which exposes operators to high levels of radiation and is very costly because of the large number of radioactive waste containers that need to be characterized at a nuclear facility. An alternative methodology to approach this problem consists in obtaining empirical correlations between some radionuclides that can be measured directly – such as {sup 60}Co and {sup 137}Cs, therefore designated as Key Nuclides (KNs) – and the DTMs. This methodology, denominated Scaling Factor, was applied in the scope of the present work in order to obtain Scaling Factors or Correlation Functions for the most important radioactive wastes with low and intermediate-activity level from the IEA-R1 nuclear research reactor. (author)

  6. 供水管网水样R2 A培养基细菌总数测定及其影响因素探究%Influencing Factors and Determination of Total Bacterial Count of Water Samples on R2 A Medium in Water Supply Distribution System

    Institute of Scientific and Technical Information of China (English)

    李文明; 李伟英; 陆辉; 乔羽; 王峰

    2014-01-01

    满足饮用水卫生标准的城市给水处理厂净水在输送过程中受到污染,致使管网水中细菌的重新生长和繁殖,从而导致饮用水水质存在安全隐患。以南方某城市管网为研究对象,运用ExpAssoc模型对管网水中细菌菌落总数与细菌出现概率进行模拟,并探讨了管网水的温度、浊度、余氯三个常规指标与水样细菌总数之间的关系。结果表明ExpAssoc模型可以较好地模拟管网水中细菌菌落总数和细菌出现概率的关系,相关系数R2均大于0.97。水温与管网水细菌菌落总数呈正相关关系;管网水高浊度与细菌出现频率亦存在正相关性。余氯对管网水细菌存在水平确实存在影响,当余氯量小于1.0 mg/L时,细菌出现率为100%;当余氯量大于1.0 mg/L时,细菌的出现与余氯值并不相关,呈随机分布状态。%Clean water from the water treatment plants could be polluted during transportation,which leads to the regrowth of bacteria and the potential risk of drinking water safety. The temperature,turbidity,residual chlorine and the total bacterial count of water samples on R2A medium in the water supply distribution system (WSDS)of some southern city were investigated and the total bacterial count of water samples on R2A medium in WSDS and the bacterial appearance probability were fitted by ExpAssoc model. In the same time, influence factors were also discussed. The results indicate that the ExpAssoc model can fit well the relationship between the total bacterial count and the bacterial occurrence probability and the correlation coefficients are greater than 0.97. Additionally,the total bacterial count of water samples on R2A medium in WSDS is positively correlated with the temperature;high turbidity has a positive correlation with the high bacterial probability of bacteria in WSDS;the residual chlorine indeed has an effect on the bacterial count of water samples in WSDS;when the

  7. Application of bilinear factor models to determine water quality parameters in the optically complex waters of the Western Basin of Lake Erie using first-derivative VIS/NiR hyperspectral data

    Science.gov (United States)

    Adem Ali, K.; Ortiz, J. D.

    2012-12-01

    focuses on improving the quantification of chlorophyll a and total suspended matter (TSM), by adopting bilinear factor models to link the various CPAs to their respective VIS/NiR spectral signatures. Spectral matching between extracted spectral signature and reference spectra indicated the CPAs that govern the optical properties of the WBLE namely, cyanobacteria associated with green algae, diatoms associated with phycocyanin from the blue-green algae, and inorganic clays. Independent validation data revealed that the models can predict chlorophyll a and TSM in the WBLE with R2 of 0.75 and 0.89, respectively. The RMSE for these models are 18 % for chlorophyll a and 25 % for TSM.

  8. System performance with R407A, R407B, R407C compared to R22

    DEFF Research Database (Denmark)

    Knudsen, Hans Jørgen Høgaard

    1997-01-01

    The paper presents the results obtained by substituting R22 with mixtures of R32/R124/134a (R407A, R407B and R407C) in an existing refrigeration plant. The cooling water flow and cooling water inlet temperature together with the brine flow and brine inlet temperature have been kept on a value...... been determined.The results show that for R407C both the cooling capacity and the COP are smaller than the cooling capacity and COP for R22. The cooling capacity for R407A and for R407B is lower then the cooling capacity for R22 for brine temperatures less than 0 C and higher than the capacity for R22...

  9. Study on response modification factor R and overstrength factor Ω of Y-eccentric braced steel frame based on IDA method%基于IDA的Y形偏心支撑钢框架地震反应折减系数和超强系数

    Institute of Scientific and Technical Information of China (English)

    杨文侠; 顾强; 宋振森; 李东

    2011-01-01

    按我国现行抗震规范设计了12个不同层数和不同跨度的Y形偏心支撑钢框架算例,利用基于IDA(incremental dynamic analysis)分析的能力谱方法确定了各算例的地震反应折减系数R和超强系数Ω,分析了结构总层数和楼层高跨比对各系数的影响.研究结果表明Y形偏心支撑钢框架的设计地震作用可在我国现行抗震规范的基础上降低20%左右.%Twelve Y-eccentric braced steel frames with various stories and spans lengths were designed complying with the Chinese Seismic Code. The response modification factors R and overstrength factors of each building were evaluated by capacity spectrum method based on the global capacity envelops obtained from incremental dynamic analysis. Based on the analysis results, the effects of storey numbers and spans of frames on these factors were analyzed. The results show that the elastic design earthquake action of Y-eccentric braced steel frames can be reduced by approximately 20% on the basis of Chinese Seismic Code.

  10. 76 FR 72869 - Proposed Establishment of Restricted Areas R-5402, R-5403A, R-5403B, R-5403C, R-5403D, R-5403E...

    Science.gov (United States)

    2011-11-28

    ... Federal Aviation Administration 14 CFR Part 73 Proposed Establishment of Restricted Areas R-5402, R-5403A, R- 5403B, R-5403C, R-5403D, R-5403E, and R-5403F; Devils Lake, ND AGENCY: Federal Aviation... Camp Grafton Range, the existing R-5401 restricted area surrounding the range is inadequate to...

  11. J. R. R. Tolkien. A Marxist Reading

    OpenAIRE

    Stefán Gestur Stefánsson 1982

    2014-01-01

    J. R. R. Tolkien is a world renowned writer that is credited with the revival of the fantasy genre with his hobbit driven epics. His works have sold in the hundreds of millions and his novels have been transposed to films and comics which have been successful in their own right. With such exposure it is inevitable for his works to exert an influence on its audience. To criticize Tolkien’s work with the aim of getting a fuller understanding of both the author J. R. R. Tolkien and his works cal...

  12. Circulating microRNAs, miR-939, miR-595, miR-519d and miR-494, Identify Cirrhotic Patients with HCC.

    Directory of Open Access Journals (Sweden)

    Francesca Fornari

    Full Text Available The performance of circulating biomarkers for the diagnosis of hepatocellular carcinoma (HCC is sub-optimal. In this study we tested circulating microRNAs as biomarkers for HCC in cirrhotic patients by performing a two stage study: a discovery phase conducted by microarray and a validation phase performed by qRT-PCR in an independent series of 118 patients. Beside miRNAs emerged from the discovery phase, miR-21, miR-221, miR-519d were also tested in the validation setting on the basis of literary and tissue findings. Deregulated microRNAs were assayed in HCC-derived cells in the intracellular compartment, cell culture supernatant and exosomal fraction. Serum and tissue microRNA levels were compared in 14 patients surgically treated for HCC. From the discovery study, it emerged that seven circulating microRNAs were differentially expressed in cirrhotic patients with and without HCC. In the validation set, miR-939, miR-595 and miR-519d were shown to differentiate cirrhotic patients with and without HCC. MiR-939 and miR-595 are independent factors for HCC. ROC curves of miR-939, miR-595 and miR-519d displayed that AUC was higher than AFP. An exosomal secretion of miR-519d, miR-21, miR-221 and miR-1228 and a correlation between circulating and tissue levels of miR-519d, miR-494 and miR-21 were found in HCC patients. Therefore, we show that circulating microRNAs deserve attention as non-invasive biomarkers in the diagnostic setting of HCC and that exosomal secretion contributes to discharging a subset of microRNAs into the extracellular compartment.

  13. Circulating microRNAs, miR-939, miR-595, miR-519d and miR-494, Identify Cirrhotic Patients with HCC

    Science.gov (United States)

    Fornari, Francesca; Ferracin, Manuela; Trerè, Davide; Milazzo, Maddalena; Marinelli, Sara; Galassi, Marzia; Venerandi, Laura; Pollutri, Daniela; Patrizi, Clarissa; Borghi, Alberto; Foschi, Francesco G.; Stefanini, Giuseppe F.; Negrini, Massimo; Bolondi, Luigi; Gramantieri, Laura

    2015-01-01

    The performance of circulating biomarkers for the diagnosis of hepatocellular carcinoma (HCC) is sub-optimal. In this study we tested circulating microRNAs as biomarkers for HCC in cirrhotic patients by performing a two stage study: a discovery phase conducted by microarray and a validation phase performed by qRT-PCR in an independent series of 118 patients. Beside miRNAs emerged from the discovery phase, miR-21, miR-221, miR-519d were also tested in the validation setting on the basis of literary and tissue findings. Deregulated microRNAs were assayed in HCC-derived cells in the intracellular compartment, cell culture supernatant and exosomal fraction. Serum and tissue microRNA levels were compared in 14 patients surgically treated for HCC. From the discovery study, it emerged that seven circulating microRNAs were differentially expressed in cirrhotic patients with and without HCC. In the validation set, miR-939, miR-595 and miR-519d were shown to differentiate cirrhotic patients with and without HCC. MiR-939 and miR-595 are independent factors for HCC. ROC curves of miR-939, miR-595 and miR-519d displayed that AUC was higher than AFP. An exosomal secretion of miR-519d, miR-21, miR-221 and miR-1228 and a correlation between circulating and tissue levels of miR-519d, miR-494 and miR-21 were found in HCC patients. Therefore, we show that circulating microRNAs deserve attention as non-invasive biomarkers in the diagnostic setting of HCC and that exosomal secretion contributes to discharging a subset of microRNAs into the extracellular compartment. PMID:26509672

  14. R in a nutshell

    CERN Document Server

    Adler, Joseph

    2010-01-01

    Why learn R? Because it's rapidly becoming the standard for developing statistical software. R in a Nutshell provides a quick and practical way to learn this increasingly popular open source language and environment. You'll not only learn how to program in R, but also how to find the right user-contributed R packages for statistical modeling, visualization, and bioinformatics. The author introduces you to the R environment, including the R graphical user interface and console, and takes you through the fundamentals of the object-oriented R language. Then, through a variety of practical examp

  15. ITIL (R) - General Overview

    OpenAIRE

    Jašek, Roman; Králík, Lukáš; Nožička, Jakub

    2015-01-01

    The paper presents the reader into the issue of ITIL (R) and provides it as a basic overview of the concepts, terminology and philosophyof IT Service management. All this information is contained in 5 key ITIL (R) publications on around 1400 pages. The aim therefore is a brief summary of the issue, which also serves as an introduction to the following articles (Differences Between ITIL (R) v2 and ITIL (R) v3, ITIL (R) and Information Security, ITIL (R) Tools and ITIL (R) Implementation).

  16. ITIL (R) - General Overview

    OpenAIRE

    Jašek, Roman; Králík, Lukáš; Nožička, Jakub

    2015-01-01

    The paper presents the reader into the issue of ITIL (R) and provides it as a basic overview of the concepts, terminology and philosophyof IT Service management. All this information is contained in 5 key ITIL (R) publications on around 1400 pages. The aim therefore is a brief summary of the issue, which also serves as an introduction to the following articles (Differences Between ITIL (R) v2 and ITIL (R) v3, ITIL (R) and Information Security, ITIL (R) Tools and ITIL (R) Implementation).

  17. The crystal structures of apo and cAMP-bound GlxR from Corynebacterium glutamicum reveal structural and dynamic changes upon cAMP binding in CRP/FNR family transcription factors.

    Directory of Open Access Journals (Sweden)

    Philip D Townsend

    Full Text Available The cyclic AMP-dependent transcriptional regulator GlxR from Corynebacterium glutamicum is a member of the super-family of CRP/FNR (cyclic AMP receptor protein/fumarate and nitrate reduction regulator transcriptional regulators that play central roles in bacterial metabolic regulatory networks. In C. glutamicum, which is widely used for the industrial production of amino acids and serves as a non-pathogenic model organism for members of the Corynebacteriales including Mycobacterium tuberculosis, the GlxR homodimer controls the transcription of a large number of genes involved in carbon metabolism. GlxR therefore represents a key target for understanding the regulation and coordination of C. glutamicum metabolism. Here we investigate cylic AMP and DNA binding of GlxR from C. glutamicum and describe the crystal structures of apo GlxR determined at a resolution of 2.5 Å, and two crystal forms of holo GlxR at resolutions of 2.38 and 1.82 Å, respectively. The detailed structural analysis and comparison of GlxR with CRP reveals that the protein undergoes a distinctive conformational change upon cyclic AMP binding leading to a dimer structure more compatible to DNA-binding. As the two binding sites in the GlxR homodimer are structurally identical dynamic changes upon binding of the first ligand are responsible for the allosteric behavior. The results presented here show how dynamic and structural changes in GlxR lead to optimization of orientation and distance of its two DNA-binding helices for optimal DNA recognition.

  18. Practical experience with R32 mixtures as replacement substances for R22 and R502; Praxiserfahrungen mit R32-Gemischen als Austauschstoffe fuer R22 und R502

    Energy Technology Data Exchange (ETDEWEB)

    Schwennesen, K. [Deutsche ICI GmbH, Frankfurt am Main (Germany)

    1995-12-31

    Like R11 and R12, the refrigerant R502 will soon belong to the past and the steps for the prohibition of use of R22 have already been taken. Due to both its thermo-physical properties and its relatively low greenhouse gas potential, R32 is an important part of replacement refrigerants compatible with the ozone layer for both R22 and R502. There is a report on practical experience with R407A and R407C here. (orig.) [Deutsch] Das Kaeltemittel R 502 wird, wie R 11 und R 12, in naechster Zukunft der Vergangenheit angehoeren und auch fuer R 22 sind die Schritte zu Verwendungsverboten bereits festgelegt. R 32 ist sowohl aufgrund seiner thermophysikalischen Eigenschaften als auch wegen seines relative niedrigen Treibhauspotentials eine bedeutende Komponente in ozonvertraeglichen Austauschkaeltemitteln sowohl fuer R 22 als uach fuer R 502. Ueber Praxiserfahrungen mit R 407A und R 407C wird hier berichtet. (orig.)

  19. Discovery of a Potent, Selective, Orally Bioavailable, and Efficacious Novel 2-(Pyrazol-4-ylamino)-pyrimidine Inhibitor of the Insulin-like Growth Factor-1 Receptor (IGF-1R).

    Science.gov (United States)

    Degorce, Sébastien L; Boyd, Scott; Curwen, Jon O; Ducray, Richard; Halsall, Christopher T; Jones, Clifford D; Lach, Franck; Lenz, Eva M; Pass, Martin; Pass, Sarah; Trigwell, Catherine

    2016-05-26

    Optimization of cellular lipophilic ligand efficiency (LLE) in a series of 2-anilino-pyrimidine IGF-1R kinase inhibitors led to the identification of novel 2-(pyrazol-4-ylamino)-pyrimidines with improved physicochemical properties. Replacement of the imidazo[1,2-a]pyridine group of the previously reported inhibitor 3 with the related pyrazolo[1,5-a]pyridine improved IGF-1R cellular potency. Substitution of the amino-pyrazole group was key to obtaining excellent kinase selectivity and pharmacokinetic parameters suitable for oral dosing, which led to the discovery of (2R)-1-[4-(4-{[5-chloro-4-(pyrazolo[1,5-a]pyridin-3-yl)-2-pyrimidinyl]amino}-3,5-dimethyl-1H-pyrazol-1-yl)-1-piperidinyl]-2-hydroxy-1-propanone (AZD9362, 28), a novel, efficacious inhibitor of IGF-1R.

  20. R graphs cookbook

    CERN Document Server

    Abedin, Jaynal

    2014-01-01

    Targeted at those with an existing familiarity with R programming, this practical guide will appeal directly to programmers interested in learning effective data visualization techniques with R and a wide-range of its associated libraries.

  1. Comparison of Body Mass Index (BMI, Body Adiposity Index (BAI, Waist Circumference (WC, Waist-To-Hip Ratio (WHR and Waist-To-Height Ratio (WHtR as predictors of cardiovascular disease risk factors in an adult population in Singapore.

    Directory of Open Access Journals (Sweden)

    Benjamin Chih Chiang Lam

    Full Text Available Excess adiposity is associated with cardiovascular disease (CVD risk factors such as hypertension, diabetes mellitus and dyslipidemia. Amongst the various measures of adiposity, the best one to help predict these risk factors remains contentious. A novel index of adiposity, the Body Adiposity Index (BAI was proposed in 2011, and has not been extensively studied in all populations. Therefore, the purpose of this study is to compare the relationship between Body Mass Index (BMI, Waist Circumference (WC, Waist-to-Hip Ratio (WHR, Waist-to-Height Ratio (WHtR, Body Adiposity Index (BAI and CVD risk factors in the local adult population.This is a cross sectional study involving 1,891 subjects (Chinese 59.1% Malay 22.2%, Indian 18.7%, aged 21-74 years, based on an employee health screening (2012 undertaken at a hospital in Singapore. Anthropometric indices and CVD risk factor variables were measured, and Spearman correlation, Receiver Operating Characteristic (ROC curves and multiple logistic regressions were used. BAI consistently had the lower correlation, area under ROC and odd ratio values when compared with BMI, WC and WHtR, although differences were often small with overlapping 95% confidence intervals. After adjusting for BMI, BAI did not further increase the odds of CVD risk factors, unlike WC and WHtR (for all except hypertension and low high density lipoprotein cholesterol. When subjects with the various CVD risk factors were grouped according to established cut-offs, a BMI of ≥23.0 kg/m2 and/or WHtR ≥0.5 identified the highest proportion for all the CVD risk factors in both genders, even higher than a combination of BMI and WC.BAI may function as a measure of overall adiposity but it is unlikely to be better than BMI. A combination of BMI and WHtR could have the best clinical utility in identifying patients with CVD risk factors in an adult population in Singapore.

  2. Metaprogramming in R

    DEFF Research Database (Denmark)

    Mailund, Thomas

    2017-01-01

    Learn how to manipulate functions and expressions to modify how the R language interprets itself. This book is an introduction to metaprogramming in the R language, so you will write programs to manipulate other programs. Metaprogramming in R shows you how to treat code as data that you can...

  3. 圈4C 的(r1,r2,r3,r4)−冠的优美性%The gracefulness of the (r1, r2, r3, r4)−corona of the cycle 4C

    Institute of Scientific and Technical Information of China (English)

    吴跃生

    2012-01-01

      讨论了圈4C 的( r r 21,,, r r 43)−冠的优美性,用构造性的方法给出了圈4C 的( r r 21,,, r r 43)−冠的优美标号。证明了圈4C 的( r r 21,,, r r 43)−冠都是交错图。%  Discussed the gracefulness of the( r r 2 1 , , , r r 4 3 )−corona of the cycle 4C .The graceful labeling was given.Proved that the( r r 2 1 , , , r r 4 3 )−corona of the cycle 4C are graceful graph.

  4. Restoration of miR-143 expression could inhibit migration and growth of MDA-MB-468 cells through down-regulating the expression of invasion-related factors.

    Science.gov (United States)

    Tavanafar, Fatemeh; Safaralizadeh, Reza; Hosseinpour-Feizi, Mohammad Ali; Mansoori, Behzad; Shanehbandi, Dariush; Mohammadi, Ali; Baradaran, Behzad

    2017-07-01

    Breast adenocarcinoma is the second common cancer in women the incidence of which is increasing in many countries, especially in developing companies. In this study, miRNA143 has been replaced by vector based microRNA-143 in breast adenocarcinoma cells (MDA-MB-468) and its anti-cancer effects on breast adenocarcinoma cells have been evaluated. The pCMV-MIR-143 vector was transfected into MDA-MB-468 cells via JetPEI transfection reagent. The transfected cells were selected by IC50 concentration of Geneticin antibiotic (G418) after a 2-week treatment. To evaluate the effect of miR-143 on the inhibition of migration, scratch wound healing assay was performed. Then, the expression level of miR-143, Kras, Vimentin, CXCR4, MMP9 and E-Cadherin were measured by the qRT-PCR method. Results of MTT and wound healing assays showed that miR-143 inhibited cell growth and cell migration in miR-143 induced cell line compared with control group. The result of gene expression showed that miR-143 reduced Kras, Vimentin, CXCR4 and MMP9 expression, and increased E-Cadherin expression in miR-143 replaced cells compared to control cells. The results showed that miRNA-143 plays an important role in cell growth and migration during breast cancer development and metastasis and it can be a candidate as a therapeutic molecule in microRNA replacement therapy of breast adenocarcinoma. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Data manipulation with R

    CERN Document Server

    Abedin, Jaynal

    2014-01-01

    This book is a step-by step, example-oriented tutorial that will show both intermediate and advanced users how data manipulation is facilitated smoothly using R.This book is aimed at intermediate to advanced level users of R who want to perform data manipulation with R, and those who want to clean and aggregate data effectively. Readers are expected to have at least an introductory knowledge of R and some basic administration work in R, such as installing packages and calling them when required.

  6. Data Mashups in R

    CERN Document Server

    Leipzig, Jeremy

    2009-01-01

    This article demonstrates how the realworld data is imported, managed, visualized, and analyzed within the R statistical framework. Presented as a spatial mashup, this tutorial introduces the user to R packages, R syntax, and data structures. The user will learn how the R environment works with R packages as well as its own capabilities in statistical analysis. We will be accessing spatial data in several formats-html, xml, shapefiles, and text-locally and over the web to produce a map of home foreclosure auctions and perform statistical analysis on these events.

  7. At R207

    CERN Multimedia

    1975-01-01

    At the centre, a barrel shaped hodoscope surrounds the beams' crossing point. It was previously used for experiments R205 and R206 which did run in 1974. After their completion in mid 1975 the equipment of R205 was removed, and that of R206 was modified and rearranged to create two small angle spectrometers, one on each side of the intersection, for experiment R207 (diffraction dissociation and formation at small momentum transfer), by the CERN-Holland-Manchester Collaboration. (see also photos 7508109X and 7508113X) Here on the right, Lars Leistam.

  8. R and Matlab

    CERN Document Server

    Hiebeler, David E

    2015-01-01

    The First Book to Explain How a User of R or MATLAB Can Benefit from the OtherIn today's increasingly interdisciplinary world, R and MATLAB® users from different backgrounds must often work together and share code. R and MATLAB® is designed for users who already know R or MATLAB and now need to learn the other platform. The book makes the transition from one platform to the other as quick and painless as possible.Enables R and MATLAB Users to Easily Collaborate and Share CodeThe author covers essential tasks, such as working with matrices and vectors, writing functions and other programming co

  9. 中国区域研发效率及其影响因素研究——基于随机前沿函数的实证分析%Research on regional R&D efficiency and its influencing factors —empirical analysis based on stochastic frontier function

    Institute of Scientific and Technical Information of China (English)

    刘和东

    2011-01-01

    通过收集1998-2008年我国30个省市创新投入产出及相关影响因素的面板数据,应用随机前沿函数测度了各区域的研发效率及影响因素.发现:(1)未考虑效率影响因素时,中国区域研发效率较低;考虑影响因素后,短期效率得到提升,中期经过一个短暂的下降调整,长期进一步提升.(2)研发效率的影响因素中,政府资助对研发效率的作用,短期中促进效果不明显,中长期甚至出现负面效应.金融支持对研发效率的影响各期均显著为负.企业主体对研发效率的影响短期为负;长期中,有显著促进作用.产学研合作对研发效率的影响:短期与长期显著为负;中期正面影响不显著.FDI对研发效率的影响:短期中有显著促进作用,中期中会抑制研发效率;长期中促进效应不显著.基础设施、人力资本对研发效率有显著的促进.经济增长对研发效率随不同时期呈不显著、显著状态的正面影响.地理区位对研发效率有负面影响,短期显著,中长期不显著.在此基础上提出了有效提升区域创新效率的政策建议.%Collecting the 30 provinces in China and the related impact factors of innovation input and output factors in panel data from 1998 -2008, using stochastic frontier function, the paper measured the regional R&D efficiency and influencing factors. Found: 1.impact factors are not taken into account, the efficiency of China's regional development is lower; Considering the impact factors, short - term efficiency is enhanced, through a temporary decline in the medium - term adjustment and long - term to further enhance. 2.R&D efficiency factors, the efficiency of government- funded R&D function, short- term promoting effect was not obvious, even has negative effects in medium - long - term. Financial support for R&D efficiency of each period were significantly negative. Business of the main is negative to R&D efficiency in short - term; there is a significant

  10. Comparison and Analysis on the Trade Characteristies and Influeutial Factors of Chinese Copany's R&D Investment%跨国公司R&D投资的行业特征及影响因素的比较与分析

    Institute of Scientific and Technical Information of China (English)

    胡国珠

    2003-01-01

    跨国公司研发国际化在行业上表现出一定的不平衡性.本文对跨国公司在美国、日本、中国三国进行R&D投资所呈现的行业特征及影响因素进行比较与分析,试图探寻我国在更高层次、更宽领域引进R&D投资所应采取的措施.

  11. Discovery of 3,5-disubstituted-1H-pyrrolo[2,3-b]pyridines as potent inhibitors of the insulin-like growth factor-1 receptor (IGF-1R) tyrosine kinase

    Energy Technology Data Exchange (ETDEWEB)

    Patnaik, Samarjit; Stevens, Kirk L.; Gerding, Roseanne; Deanda, Felix; Shotwell, J. Brad; Tang, Jun; Hamajima, Toshihiro; Nakamura, Hiroko; Leesnitzer, M. Anthony; Hassell, Anne M.; Shewchuck, Lisa M.; Kumar, Rakesh; Lei, Huangshu; Chamberlain, Stanley D.; (GSKNC); (GSKPA); (GSK)

    2009-07-23

    Exploration of the SAR around a series of 3,5-disubstituted-1H-pyrrolo[2,3-b]pyridines led to the discovery of novel pyrrolopyridine inhibitors of the IGF-1R tyrosine kinase. Several compounds demonstrated nanomolar potency in enzyme and cellular mechanistic assays.

  12. Empirical Research on Factors Affecting Optimal R & D Intensity of an Enterprise%企业最优研发强度影响因素实证研究

    Institute of Scientific and Technical Information of China (English)

    徐雷

    2015-01-01

    文章的研究分为两个部分,第一部分通过二项式回归证明了企业绩效与研发强度之间呈倒U型曲线式的相关关系,从而找到了企业的“最优”研发强度;第二部分以该“最优”研发强度为被解释变量,以透明国际发布的CPI指数为解释变量,考察了经济体清廉程度与企业最优研发强度之间的关系。实证结果显示,政治清廉度与企业最优研发强度之间存在显著的正相关关系,这对提升我国企业的研发强度和研发能力具有借鉴意义。%The "optimal" R&D intensity of an enterprise is first discovered by certain binomial regression, which proves the correlativity of inverted U-shaped curve between corporate performance and R&D intensity, and then the relationship is found between economic incorruptibility and optimal R&D intensity of an enterprise by applying the above "optimal" intensity as the explained variable and the corruption perception index developed by Transparence International as the explanatory variable. The empirical result shows that there exists a positive correlativity between political incorruptibility and the optimal R&D intensity of an enterprise, which will play an important role in promoting Chinese enterprise's R&D intensity and capacity.

  13. The level of insulin growth factor-1 receptor expression is directly correlated with the tumor uptake of {sup 111}In-IGF-1(E3R) in vivo and the clonogenic survival of breast cancer cells exposed in vitro to trastuzumab (Herceptin)

    Energy Technology Data Exchange (ETDEWEB)

    Cornelissen, Bart; McLarty, Kristin; Kersemans, Veerle [Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Reilly, Raymond M. [Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Department of Medical Imaging, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Toronto General Research Institute, University Health Network Toronto, Toronto, ON, M5S 3M2 (Canada)], E-mail: raymond.reilly@utoronto.ca

    2008-08-15

    Introduction: Our objective was to define the relationships between tumor uptake of [{sup 111}In]-IGF-1 and [{sup 111}In]-IGF-1(E3R), an analogue which does not bind insulin growth factor-1 (IGF-1) binding proteins (i.e., IGFBP-3), and the level of IGF-1 receptor (IGF-1R) expression on human breast cancer (BC) xenografts in athymic mice, as well as the feasibility for tumor imaging. A second objective was to correlate IGF-1R (and HER2 density) with the cytotoxicity of trastuzumab in the absence/presence of IGFBP-3 or the IGF-1R tyrosine kinase inhibitor, AG1024. Methods: The tumor and normal tissue uptake of [{sup 111}In]-IGF-1 and [{sup 111}In]-IGF-1(E3R) were determined at 4 h postinjection in mice implanted subcutaneously with MDA-MB-231, H2N, HR2 or MCF-7/HER2-18 human BC xenografts (8.5x10{sup 4}, 1.4x10{sup 4}, 4.0x10{sup 4} and 1.0x10{sup 5} IGF-1R/cell, respectively). The effect of co-injection of IGF-1 (50 {mu}g) or IGFBP-3 (2 or 25 {mu}g) was studied. The relationship between tumor uptake of [{sup 111}In]-IGF-1(E3R) and IGF-1R density was examined. MicroSPECT/CT imaging was performed on mice with MCF-7/HER2-18 tumors injected with [{sup 111}In]-IGF-1(E3R). The surviving fraction of BC cells exposed to trastuzumab (67.5 {mu}g/ml) in the absence/presence of IGFBP-3 (1 {mu}g/ml) or the IGF-1R kinase inhibitor, AG1024 (1 or 5 {mu}g/ml), was determined. Results: [{sup 111}In]-IGF-1 was specifically taken up by MCF-7/HER2-18 xenografts; tumor uptake was decreased twofold when co-injected with IGF-1 (1.9{+-}0.1 vs. 1.0{+-}0.1 %ID/g). Co-injection of IGBP-3 decreased kidney uptake of [{sup 111}In]-IGF-1 up to twofold and increased circulating radioactivity threefold. There was a strong linear correlation (r{sup 2}=0.99) between the tumor uptake of {sup 111}In-IGF-1(E3R) and IGF-1R density. Tumor uptake ranged from 0.4{+-}0.05 %ID/g for H2N to 2.5{+-}0.5 %ID/g for MCF-7/HER2-18 xenografts. MCF-7/HER2-18 tumors were visualized by microSPECT/CT. Resistance of BC

  14. Offshoring R&D

    DEFF Research Database (Denmark)

    Hansen, Zaza Nadja Lee; Rasmussen, Lauge Baungaard

    2010-01-01

    Companies are increasingly offshoring R&D activities. Many firms, however, experience difficulties related to virtual teamwork across cultures and time zones. The research question is: How does increasing R&D offshoring impact transparency of communication structures and knowledge sharing? Using...... case studies from Danish multinational corporations with R&D activities in China, India or Eastern Europe this paper analyses the impact observed in these companies in regard to communication structures and knowledge sharing in management of offshored R&D activities. The findings show that companies...... to the complexity of the R&D activity. This paper shows that management of offshored R&D activities touches upon many key management dilemmas like trust, control and knowledge sharing....

  15. R for fledglings

    Science.gov (United States)

    Donovan, Therese; Brown, Michelle; Katz, Jonathan

    2015-01-01

    We’ve been asked to provide a short introduction to R and its utility in natural resource management. In this short introduction, we can guarantee one thing: you won’t learn R in a few days. That would be like learning to speak French in a few days. To actually learn R, you need to practice….Bode Miller didn’t win his Olympic medals without hours and hours of practice. However, in this short introduction, you can gain an appreciation for what R can do, be introduced to some key functions that you will likely use over and over again, and learn some strategies for creating scripts for automating your work. There are several excellent R books that provide much more information than this short introduction….. R has a steep learning curve, and our hope is to cover some basics to get you over the initial hump.

  16. Outsourcing R&D

    DEFF Research Database (Denmark)

    Hsuan, Juliana; Mahnke, Volker

    2011-01-01

    Outsourcing R&D is an increasingly explored corporate practice. Extant research advanced our initial understanding of its increasing importance and benefits. While the associated literature has blossomed, the enthusiasm of R&D managers is tenured by an increasing realization of the possible...... downsides, risks, and costs that come with increasing use of external sources of innovation. Here, we suggest that research on outsourcing R&D has to move towards a balanced view on the profitability of such arrangements. To this end, we offer a review of what we know and need to know about outsourcing R......&D, suggest a simple, yet integrative model on the relation between outsourcing R&D and performance, and offer a research agenda that is instrumental in guiding companies’ process-management and design strategies when seeking to benefit from the outsourcing of R&D....

  17. Outsourcing R&D

    DEFF Research Database (Denmark)

    Hsuan, Juliana; Mahnke, Volker

    2011-01-01

    Outsourcing R&D is an increasingly explored corporate practice. Extant research advanced our initial understanding of its increasing importance and benefits. While the associated literature has blossomed, the enthusiasm of R&D managers is tenured by an increasing realization of the possible...... downsides, risks, and costs that come with increasing use of external sources of innovation. Here, we suggest that research on outsourcing R&D has to move towards a balanced view on the profitability of such arrangements. To this end, we offer a review of what we know and need to know about outsourcing R......&D, suggest a simple, yet integrative model on the relation between outsourcing R&D and performance, and offer a research agenda that is instrumental in guiding companies’ process-management and design strategies when seeking to benefit from the outsourcing of R&D....

  18. r

    DEFF Research Database (Denmark)

    Koustrup, Pia

    2005-01-01

    kroppen både omhandler den tekniske færdighed, det er at rense et sår, og den omsorgsfulde fysiske og psyko-sociale pleje. Kapitlet beskriver kroniske og hyggigt forekomne sår og slutter med de mere sjældne sårtyper. Dele af beksrivelsen af sår, er ud fra en erfaringsbaseret viden, idet der endnu ikke...

  19. At R207

    CERN Multimedia

    1975-01-01

    With R207 the CERN-Holland-Manchester Collaboration studied proton-proton diffraction dissociation at small momentum transfer. This followed, at Intersection 2, the study of correlations associated with high transverse momentum particles by Daresbury-Liverpool-RHEL Collaboration (R205) and of multiplicity and rapidity distributions in diffractive collisions by CERN-Holland-Lancaster-Manchester (R206), and used part of the previous set-up.

  20. Multilevel modeling using R

    CERN Document Server

    Finch, W Holmes; Kelley, Ken

    2014-01-01

    A powerful tool for analyzing nested designs in a variety of fields, multilevel/hierarchical modeling allows researchers to account for data collected at multiple levels. Multilevel Modeling Using R provides you with a helpful guide to conducting multilevel data modeling using the R software environment.After reviewing standard linear models, the authors present the basics of multilevel models and explain how to fit these models using R. They then show how to employ multilevel modeling with longitudinal data and demonstrate the valuable graphical options in R. The book also describes models fo

  1. Jets with Variable R

    CERN Document Server

    Krohn, David; Wang, Lian-Tao

    2009-01-01

    We introduce a new class of jet algorithms designed to return conical jets with a variable Delta R radius. A specific example, in which Delta R scales as 1/pT, proves particularly useful in capturing the kinematic features of a wide variety of hard scattering processes. We implement this Delta R scaling in a sequential recombination algorithm and test it by reconstructing resonance masses and kinematic endpoints. These test cases show 10-20% improvements in signal efficiency compared to fixed Delta R algorithms. We also comment on cuts useful in reducing continuum jet backgrounds.

  2. 影响米根霉产γ-亚麻酸的几种因素%Effect of several factors of Gamma-Linolenic Acid (GLA) in Rhizopus stolonifer R316

    Institute of Scientific and Technical Information of China (English)

    朱钰; 陆合; 胡晓莉

    2007-01-01

    利用气相色谱仪对根霉属的部分菌株进行脂肪酸成分分析,发现中华根霉(Rhizopus chinensis)、米根霉(Rhizopus oryzae)和匍枝根霉(Rhizopus stolonifer)均能产生γ-亚麻酸,其中米根霉R316菌丝体中γ-亚麻酸的含量较高达11.47%,对R316的液体发酵产脂条件进行研究,发现液体摇瓶培养菌丝体的油脂含量可达53.24 %,γ-亚麻酸的含量提高到20.12%.R316菌丝体生长的最适碳源为葡萄糖、最适氮源为蛋白胨、最适培养温度20℃.但γ-亚麻酸积累的最适碳源为甘油、最适氮源是尿素、最适温度15℃.同时发现逆境是高产多不饱和脂肪酸的关键.

  3. Plasmid construction and idetification of human vascular endothelial growth factor receptor(VEGF-R3) extracellular domain 1-3Loop cDNA abstract%人类血管内皮生长因子受体VEGF-R3胞外区1-3环cDNA基因的研究

    Institute of Scientific and Technical Information of China (English)

    解宝童; 李涛

    2007-01-01

    Objective To insert VEGF-R3(FIT-4)gene fragment into cloning vector and identify it.Methods By T-A cloning,the VEGF-R3 gene fragment amplified by RT-PCR was cloned on the PGEM-T Easy plasmid vector and transfected into E.coli JM109.the recombinant clones were screened by"white-blue plaque selection" and tested by the methods of single restrictional enzyme.Results The VEGF-R3 gene fragment amplified by RT-PCR showed a smear after the electrophoresis on agarose Gel and obtained white clones by"white-blue plaque selection".The electrophoresis result of the recombinant clones tested by the single restrictional enzyme was accordant with expectant result.Conclusion The recombinant clones through the methods T-A may be used in the further gene expression and gene therapy studies.%目的 将VEGF-R3(FIT-4)基因片断插入克隆载体并进行分子生物学鉴定,对肿瘤细胞通过淋巴管转移到局部淋巴结的机制进行研究.方法 用T-A克隆的方法 将RT-PCR产物克隆入质粒载体PGEM-T Easy,转染大肠杆菌JM109,进行蓝白斑筛选,获取重组体单酶切电泳图谱.结果 经过RT-PCR扩增,得到VEGF-R3的cDNA,琼脂糖凝胶电泳显示为一条带,经蓝白斑筛选获得基因VEGF-R3的白色克隆,重组质粒单酶切电泳结果 与预期结果 一致.结论 RT-PCR产物可采用T-A克隆,获得的阳性重组体可用于进一步基因表达及基因治疗等研究.

  4. Applied multivariate statistics with R

    CERN Document Server

    Zelterman, Daniel

    2015-01-01

    This book brings the power of multivariate statistics to graduate-level practitioners, making these analytical methods accessible without lengthy mathematical derivations. Using the open source, shareware program R, Professor Zelterman demonstrates the process and outcomes for a wide array of multivariate statistical applications. Chapters cover graphical displays, linear algebra, univariate, bivariate and multivariate normal distributions, factor methods, linear regression, discrimination and classification, clustering, time series models, and additional methods. Zelterman uses practical examples from diverse disciplines to welcome readers from a variety of academic specialties. Those with backgrounds in statistics will learn new methods while they review more familiar topics. Chapters include exercises, real data sets, and R implementations. The data are interesting, real-world topics, particularly from health and biology-related contexts. As an example of the approach, the text examines a sample from the B...

  5. Examining Factors Influencing Colorectal Cancer Screening of Rural Nebraskans Using Data from Clinics Participating in an Accountable Care Organization: A Study Protocol [v1; ref status: indexed, http://f1000r.es/5me

    Directory of Open Access Journals (Sweden)

    Lufei Young

    2015-07-01

    Full Text Available Background: Although mortality rates of colorectal cancer (CRC can be significantly reduced through increased screening, rural communities are still experiencing lower rates of screening compared to urban counterparts. Understanding and eliminating barriers to cancer screening will decrease cancer burden and lead to substantial gains in quality and quantity of life for rural populations. However, existing studies have shown inconsistent findings and fail to address how contextual and provider-level factors impact CRC screening in addition to individual-level factors.  Purpose: The purpose of the study is to examine multi-level factors related to CRC screening, and providers’ perception of barriers and facilitators of CRC screening in rural patients cared for by accountable care organization (ACO clinics. Methods/Design: This is a convergent mixed method design. For the quantitative component, multiple data sources, such as electronic health records (EHRs, Area Resource File (ARF, and provider survey data, will be used to examine patient-, provider-, clinic-, and county-level factors. About 21,729 rural patients aged between 50 and 75 years who visited the participating ACO clinics in the past 12 months are included in the quantitative analysis. The qualitative methods include semi-structured in-depth interviews with healthcare professionals in selected rural clinics. Both quantitative and qualitative data will be merged for result interpretation. Quantitative data identifies “what” factors influence CRC screening, while qualitative data explores “how” these factors interact with CRC screening. The study setting is 10 ACO clinics located in nine rural Nebraska counties. Discussion: This will be the first study examining multi-level factors related to CRC screening in the new healthcare delivery system (i.e., ACO clinics in rural communities. The study findings will enhance our understanding of how the ACO model, particularly in rural

  6. Teachers’ views on professional image and influential factorsÖğretmenlerin mesleki imajlarina ilişkin görüşleri ve mesleki imaja etki eden faktörler

    OpenAIRE

    Serkan Ünsal; Birsen Bağçeci

    2016-01-01

    Nowadays, it is essential for teachers to renew themselves, change and continually pursue excellence. Thus, the core purpose of this study was to determine public and private school teachers’ views on professional image and influential factors. Within this framework, the overall objective of this study was to reveal teachers’ views on professional image, factors influencing this image, teaching profession status, profession dignity, teacher qualification and personal image. The study was base...

  7. The Social Media Factor In The Development And Promotion Of Religious Tourism İnanç Turizminin Tanıtımında ve Gelişiminde Sosyal Medya Faktörü

    Directory of Open Access Journals (Sweden)

    M. Murat YEŞİL

    2013-09-01

    Full Text Available Tourism and religion have been in co-operation with each other due to the"Hajj pilgrimage" throughout history. The concept of religious tourism of today is based on this co-operation. All sectors of tourism, including religious tourism, need publicity first and then to market their destinations and the travel programs for survival. The emerging "social media networks " that appeared after the developments in Internet technology are thought to be useful tools in both fields. Scientific researches have discovered a strong relationship between the use of social media and consumers' purchasing decisions or renunciation. This relationship can be used as an efficient support in promoting and marketing of destinations and tour programs in religious tourism industry. According to reseachers, people, who share their past travel experiences with friends and relatives on the social media, can be effective on the travel plans of others, from choosing destinations to hotels and restaurants. Social media is seen as a great tool of promotion and marketing for all kinds of businesses but like any other tools, social media have useful and harmful aspects. If they are used cleverly, social media can carry businesses to distant horizons beyond their imaginations but improper use of social media can do more harm than good. There is no study which examines the role of social media in promoting and development of religious tourism. The purpose of this study is to research the importance of the role that social media can play in the development and promotion of religious tourism and produce solutions to probable problems that may arise. Turizm ile din tarih boyunca “Hac ziyaretleri” sayesindebirbirleriyle işbirliği halinde olmuşlar. Bugünkü inanç turizmikavramının temeli bu işbirliğine dayanmaktadır. İnanç turizmi de dahilolmak üzere turizmin tüm sektörlerinin varlıklarını sürdürebilmeleriiçin önce tanıtıma sonra da destinasyonlarını ve

  8. Factors Impacting Knowledge Sharing

    DEFF Research Database (Denmark)

    Schulzmann, David; Slepniov, Dmitrij

    The purpose of this paper is to examine various factors affecting knowledge sharing at the R&D center of a Western MNE in China. The paper employs qualitative methodology and is based on the action research and case study research techniques. The findings of the paper advance our understanding...... about factors that affect knowledge sharing. The main emphasis is given to the discussion on how to improve knowledge sharing in global R&D organizations....