WorldWideScience

Sample records for proximal promoter regions

  1. Kmt5a Controls Hepatic Metabolic Pathways by Facilitating RNA Pol II Release from Promoter-Proximal Regions

    Directory of Open Access Journals (Sweden)

    Kostas C. Nikolaou

    2017-07-01

    Full Text Available H4K20 monomethylation maintains genome integrity by regulating proper mitotic condensation, DNA damage response, and replication licensing. Here, we show that, in non-dividing hepatic cells, H4K20Me1 is specifically enriched in active gene bodies and dynamically regulated by the antagonistic action of Kmt5a methylase and Kdm7b demethylase. In liver-specific Kmt5a-deficient mice, reduced levels of H4K20Me1 correlated with reduced RNA Pol II release from promoter-proximal regions. Genes regulating glucose and fatty acid metabolism were most sensitive to impairment of RNA Pol II release. Downregulation of glycolytic genes resulted in an energy starvation condition partially compensated by AMP-activated protein kinase (AMPK activation and increased mitochondrial activity. This metabolic reprogramming generated a highly sensitized state that, upon different metabolic stress conditions, quickly aggravated into a senescent phenotype due to ROS overproduction-mediated oxidative DNA damage. The results illustrate how defects in the general process of RNA Pol II transition into a productive elongation phase can trigger specific metabolic changes and genome instability.

  2. Promoting proximal formative assessment with relational discourse

    Science.gov (United States)

    Scherr, Rachel E.; Close, Hunter G.; McKagan, Sarah B.

    2012-02-01

    The practice of proximal formative assessment - the continual, responsive attention to students' developing understanding as it is expressed in real time - depends on students' sharing their ideas with instructors and on teachers' attending to them. Rogerian psychology presents an account of the conditions under which proximal formative assessment may be promoted or inhibited: (1) Normal classroom conditions, characterized by evaluation and attention to learning targets, may present threats to students' sense of their own competence and value, causing them to conceal their ideas and reducing the potential for proximal formative assessment. (2) In contrast, discourse patterns characterized by positive anticipation and attention to learner ideas increase the potential for proximal formative assessment and promote self-directed learning. We present an analysis methodology based on these principles and demonstrate its utility for understanding episodes of university physics instruction.

  3. Characterization of the cis elements in the proximal promoter regions of the anthocyanin pathway genes reveals a common regulatory logic that governs pathway regulation.

    Science.gov (United States)

    Zhu, Zhixin; Wang, Hailong; Wang, Yiting; Guan, Shan; Wang, Fang; Tang, Jingyu; Zhang, Ruijuan; Xie, Lulu; Lu, Yingqing

    2015-07-01

    Cellular activities such as compound synthesis often require the transcriptional activation of an entire pathway; however, the molecular mechanisms underlying pathway activation have rarely been explained. Here, the cis regulatory architecture of the anthocyanin pathway genes targeted by the transcription factor (TF) complex including MYB, bHLH, and WDR was systematically analysed in one species and the findings extended to others. In Ipomoea purpurea, the IpMYB1-IpbHLH2-IpWDR1 (IpMBW) complex was found to be orthologous to the PAP1-GL3-TTG1 (AtPGT) complex of Arabidopsis thaliana, and interacted with a 7-bp MYB-recognizing element (MRE) and a 6-bp bHLH-recognizing element (BRE) at the proximal promoter region of the pathway genes. There was little transcription of the gene in the absence of the MRE or BRE. The cis elements identified experimentally converged on two syntaxes, ANCNNCC for MREs and CACN(A/C/T)(G/T) for BREs, and our bioinformatic analysis showed that these were present within anthocyanin gene promoters in at least 35 species, including both gymnosperms and angiosperms. For the anthocyanin pathway, IpMBW and AtPGT recognized the interspecific promoters of both early and later genes. In A. thaliana, the seed-specific TF complex (TT2, TT8, and TTG1) may regulate all the anthocyanin pathway genes, in addition to the proanthocyanidin-specific BAN. When multiple TF complexes in the anthocyanin pathway were compared, the cis architecture played a role larger than the TF complex in determining the variation in promoter activity. Collectively, a cis logic common to the pathway gene promoters was found, and this logic is essential for the trans factors to regulate the pathway. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  4. A positioned +1 nucleosome enhances promoter-proximal pausing

    OpenAIRE

    Jimeno-Gonz?lez, Silvia; Ceballos-Ch?vez, Mar?a; Reyes, Jos? C.

    2015-01-01

    Chromatin distribution is not uniform along the human genome. In most genes there is a promoter-associated nucleosome free region (NFR) followed by an array of nucleosomes towards the gene body in which the first (+1) nucleosome is strongly positioned. The function of this characteristic chromatin distribution in transcription is not fully understood. Here we show in vivo that the +1 nucleosome plays a role in modulating RNA polymerase II (RNAPII) promoter-proximal pausing. When a +1 nucleoso...

  5. Temporal Proximity Promotes Integration of Overlapping Events.

    Science.gov (United States)

    Zeithamova, Dagmar; Preston, Alison R

    2017-08-01

    Events with overlapping elements can be encoded as two separate representations or linked into an integrated representation, yet we know little about the conditions that promote one form of representation over the other. Here, we tested the hypothesis that the proximity of overlapping events would increase the probability of integration. Participants first established memories for house-object and face-object pairs; half of the pairs were learned 24 hr before an fMRI session, and the other half 30 min before the session. During scanning, participants encoded object-object pairs that overlapped with the initial pairs acquired on the same or prior day. Participants were also scanned as they made inference judgments about the relationships among overlapping pairs learned on the same or different day. Participants were more accurate and faster when inferring relationships among memories learned on the same day relative to those acquired across days, suggesting that temporal proximity promotes integration. Evidence for reactivation of existing memories-as measured by a visual content classifier-was equivalent during encoding of overlapping pairs from the two temporal conditions. In contrast, evidence for integration-as measured by a mnemonic strategy classifier from an independent study [Richter, F. R., Chanales, A. J. H., & Kuhl, B. A. Predicting the integration of overlapping memories by decoding mnemonic processing states during learning. Neuroimage, 124, 323-335, 2016]-was greater for same-day overlapping events, paralleling the behavioral results. During inference itself, activation patterns further differentiated when participants were making inferences about events acquired on the same day versus across days. These findings indicate that temporal proximity of events promotes integration and further influences the neural mechanisms engaged during inference.

  6. The regional dimension of intergenerational proximity in the Netherlands

    NARCIS (Netherlands)

    van der Pers, Marieke; Mulder, Clara H.

    Previous research has shown the impact of individual characteristics on intergenerational proximity but has largely ignored the regional dimension of such proximity. In this paper, we examine the regional variation in intergenerational proximity in the Netherlands. We address this issue by

  7. Genetic variation in the proximal promoter of ABC and SLC superfamilies: liver and kidney specific expression and promoter activity predict variation.

    Directory of Open Access Journals (Sweden)

    Stephanie E Hesselson

    2009-09-01

    Full Text Available Membrane transporters play crucial roles in the cellular uptake and efflux of an array of small molecules including nutrients, environmental toxins, and many clinically used drugs. We hypothesized that common genetic variation in the proximal promoter regions of transporter genes contribute to observed variation in drug response. A total of 579 polymorphisms were identified in the proximal promoters (-250 to +50 bp and flanking 5' sequence of 107 transporters in the ATP Binding Cassette (ABC and Solute Carrier (SLC superfamilies in 272 DNA samples from ethnically diverse populations. Many transporter promoters contained multiple common polymorphisms. Using a sliding window analysis, we observed that, on average, nucleotide diversity (pi was lowest at approximately 300 bp upstream of the transcription start site, suggesting that this region may harbor important functional elements. The proximal promoters of transporters that were highly expressed in the liver had greater nucleotide diversity than those that were highly expressed in the kidney consistent with greater negative selective pressure on the promoters of kidney transporters. Twenty-one promoters were evaluated for activity using reporter assays. Greater nucleotide diversity was observed in promoters with strong activity compared to promoters with weak activity, suggesting that weak promoters are under more negative selective pressure than promoters with high activity. Collectively, these results suggest that the proximal promoter region of membrane transporters is rich in variation and that variants in these regions may play a role in interindividual variation in drug disposition and response.

  8. Promoting regional mobility

    DEFF Research Database (Denmark)

    Jensen, Anne

    Pricing of transport has been part of EU's common transport policy since this gained momentum in the early 1990s. Since then, it has been closely connected to the trans-European transport network (TEN-T) and to rising demands of efficient mobility systems at a local, regional and Community scale....... Development of pricing policies is contested at Community level and has taken place in a clash between different policy rationalities. Significantly though, the effects of the pricing policies are closely related to regional mobility systems, e.g. through financing large trans-border infrastructure projects...... and establishing common technical charging systems thus changing the conditions for regional mobility. This paper explores how policies of infrastructure pricing shape new ways of governing mobility which influences trans-border, regional policy-making. The key findings are that there is a tendency to include...

  9. In vitro footprinting of promoter regions within supercoiled plasmid DNA.

    Science.gov (United States)

    Sun, Daekyu

    2010-01-01

    Polypurine/polypyrimidine (pPu/pPy) tracts, which exist in the promoter regions of many growth-related genes, have been proposed to be very dynamic in their conformation. In this chapter, we describe a detailed protocol for DNase I and S1 nuclease footprinting experiments with supercoiled plasmid DNA containing the promoter regions to probe whether there are conformational transitions to B-type DNA, melted DNA, and G-quadruplex structures within this tract. This is demonstrated with the proximal promoter region of the human vascular endothelial growth factor (VEGF) gene, which also contains multiple binding sites for Sp1 and Egr-1 transcription factors.

  10. Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans

    DEFF Research Database (Denmark)

    Mertz-Nielsen, Anette; Hillingsø, J; Bukhave, Klaus

    1996-01-01

    experiments. Also the combination of omeprazole and ranitidine increased (p=0.05) duodenal bicarbonate secretion, while ranitidine alone caused no change in either basal or stimulated secretion. In the stomach basal as well as vagally stimulated bicarbonate secretion was independent of the means of acid......The proton pump inhibitor, omeprazole, surprisingly resulted in higher rates of proximal duodenal mucosal bicarbonate secretion than previously reported using an H-2 receptor antagonist for gastric acid inhibition. Gastroduodenal perfusions were performed in healthy volunteers to evaluate whether...... this incidental finding is explained by more potent gastric acid inhibition by omeprazole or might be caused by the different mode of drug action. Basal and stimulated gastric and duodenal bicarbonate secretion rates were measured in the same subjects in control experiments (n=17) and after pretreatment with high...

  11. Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans

    DEFF Research Database (Denmark)

    Mertz-Nielsen, A; Hillingsø, Jens; Bukhave, K

    1996-01-01

    The proton pump inhibitor, omeprazole, surprisingly resulted in higher rates of proximal duodenal mucosal bicarbonate secretion than previously reported using an H2 receptor antagonist for gastric acid inhibition. Gastroduodenal perfusions were performed in healthy volunteers to evaluate whether...... this incidental finding is explained by more potent gastric acid inhibition by omeprazole or might be caused by the different mode of drug action. Basal and stimulated gastric and duodenal bicarbonate secretion rates were measured in the same subjects in control experiments (n = 17) and after pretreatment...... with high dose omeprazole (n = 17) and ranitidine (n = 9), respectively, by use of a technique permitting simultaneous measurements. Concentrations of bicarbonate were measured in the respective effluents by the method of back titration. Both omeprazole and ranitidine completely inhibited gastric acid...

  12. [Ultrastructure of the proximal neurosecretory contact region in a sturgeon].

    Science.gov (United States)

    Belenkiĭ, M A

    1976-01-01

    The proximal neurosecretory contact region (PCR), a homologue of the tetrapoda median eminence occupies the rostral and chiefly the ventral surfaces of the hypothalamic tuber cinereum. Three types of granule-containing neurosecretory fibres and their terminals have been found in the PCR with the electron microscope. Peptidergic, A1 and A2 type fibres contain granules of 120--300 nm and 100--170 nm in diameter, correspondingly, and monoaminergic B fibres have granules of 80--100 nm in diameter. Neurosecretory terminals and tanycyte vascular "endfeet" make contacts with a 70 nm thick outer basement membrane of the primary portal capillaries. Some thin horizontally oriented tanycyte branches form a multiserial layer bordering the external zone of the PCR from the preoptico-hypophyseal tract. Few neuroglial cells with pale cytoplasm and numerous lysosomes and lipofuscin granules are seen there. It is hypothesized that, like in other vertebrates, in the PCR of Acipenseridae both peptide and monoamine hypophysiotropic neurohormones may be discharged in the portal circulation to affect the functional activity of glandular cells of the pars distalis.

  13. The theoretical simulation on electrostatic distribution of 1st proximity region in proximity focusing low-light-level image intensifier

    Science.gov (United States)

    Zhang, Liandong; Bai, Xiaofeng; Song, De; Fu, Shencheng; Li, Ye; Duanmu, Qingduo

    2015-03-01

    Low-light-level night vision technology is magnifying low light level signal large enough to be seen by naked eye, which uses the photons - photoelectron as information carrier. Until the micro-channel plate was invented, it has been possibility for the realization of high performance and miniaturization of low-light-level night vision device. The device is double-proximity focusing low-light-level image intensifier which places a micro-channel plate close to photocathode and phosphor screen. The advantages of proximity focusing low-light-level night vision are small size, light weight, small power consumption, no distortion, fast response speed, wide dynamic range and so on. It is placed parallel to each other for Micro-channel plate (both sides of it with metal electrode), the photocathode and the phosphor screen are placed parallel to each other. The voltage is applied between photocathode and the input of micro-channel plate when image intensifier works. The emission electron excited by photo on the photocathode move towards to micro-channel plate under the electric field in 1st proximity focusing region, and then it is multiplied through the micro-channel. The movement locus of emission electrons can be calculated and simulated when the distributions of electrostatic field equipotential lines are determined in the 1st proximity focusing region. Furthermore the resolution of image tube can be determined. However the distributions of electrostatic fields and equipotential lines are complex due to a lot of micro-channel existing in the micro channel plate. This paper simulates electrostatic distribution of 1st proximity region in double-proximity focusing low-light-level image intensifier with the finite element simulation analysis software Ansoft maxwell 3D. The electrostatic field distributions of 1st proximity region are compared when the micro-channel plates' pore size, spacing and inclination angle ranged. We believe that the electron beam movement

  14. TGF-? maintains dormancy of prostatic stem cells in the proximal region of ducts

    OpenAIRE

    Salm, Sarah N.; Patricia E Burger; Coetzee, Sandra; Goto, Ken; Moscatelli, David; Wilson, E. Lynette

    2005-01-01

    We have previously shown that prostatic stem cells are located in the proximal region of mouse prostatic ducts. Here, we show that this region responds differently to transforming growth factor (TGF)-? than the distal ductal region and that under physiological conditions androgens and TGF-? are crucial overall regulators of prostatic tissue homeostasis. This conclusion is supported by the observations showing that high levels of TGF-? signaling are present in the quiescent proximal region of ...

  15. A conserved TATA-less proximal promoter drives basal transcription from the urokinase-type plasminogen activator receptor gene

    DEFF Research Database (Denmark)

    Soravia, E; Grebe, A; De Luca, P

    1995-01-01

    have cloned an uPAR DNA segment containing upstream regulatory sequences from both the human and murine genomes. We report that a proximal promoter, contained within 180 bp from the major transcription start sites of the human uPAR gene, drives basal transcription. This region lacks TATA and CAAT boxes......The urokinase-type plasminogen activator receptor (uPAR) focuses at the cell surface the activation of pro-uPA and, hence, the formation of plasmin, thus enhancing directional extracellular proteolysis. To characterize the transcriptional regulatory mechanisms that control receptor expression, we...

  16. Promotion of the region by foreign investment

    OpenAIRE

    Miroslaw Acewicz

    2013-01-01

    Globalization of the world usually starts with the economic, capital and production relations. Locating foreign investment in different regions starts their promotion. Self-promotion just by the sheer existence of something in a certain environment is implemented identity and image dimensions. Pomotion identity is the identity of the region in the context of changes of its economic and social potential, whereas an image is a visible sign of wealth and the success of the entire territory perce...

  17. Analysis of the AHR gene proximal promoter GGGGC-repeat polymorphism in lung, breast, and colon cancer

    Energy Technology Data Exchange (ETDEWEB)

    Spink, Barbara C. [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Bloom, Michael S. [Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States); Wu, Susan [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Sell, Stewart; Schneider, Erasmus [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States); Ding, Xinxin [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States); Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States); Spink, David C., E-mail: spink@wadsworth.org [Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY 12201 (United States)

    2015-01-01

    The aryl hydrocarbon receptor (AhR) regulates expression of numerous genes, including those of the CYP1 gene family. With the goal of determining factors that control AHR gene expression, our studies are focused on the role of the short tandem repeat polymorphism, (GGGGC){sub n}, located in the proximal promoter of the human AHR gene. When luciferase constructs containing varying GGGGC repeats were transfected into cancer cell lines derived from the lung, colon, and breast, the number of GGGGC repeats affected AHR promoter activity. The number of GGGGC repeats was determined in DNA from 327 humans and from 38 samples representing 5 species of non-human primates. In chimpanzees and 3 species of macaques, only (GGGGC){sub 2} alleles were observed; however, in western gorilla, (GGGGC){sub n} alleles with n = 2, 4, 5, 6, 7, and 8 were identified. In all human populations examined, the frequency of (GGGGC){sub n} was n = 4 > 5 ≫ 2, 6. When frequencies of the (GGGGC){sub n} alleles in DNA from patients with lung, colon, or breast cancer were evaluated, the occurrence of (GGGGC){sub 2} was found to be 8-fold more frequent among lung cancer patients in comparison with its incidence in the general population, as represented by New York State neonates. Analysis of matched tumor and non-tumor DNA samples from the same individuals provided no evidence of microsatellite instability. These studies indicate that the (GGGGC){sub n} short tandem repeats are inherited, and that the (GGGGC){sub 2} allele in the AHR proximal promoter region should be further investigated with regard to its potential association with lung cancer susceptibility. - Highlights: • The AHR proximal promoter contains a polymorphism, (GGGGC){sub n}, where n = 4 > 5 ≫ 2, 6 • Matched tumor and non-tumor DNA did not show (GGGGC){sub n} microsatellite instability • AHR promoter activity of a construct with (GGGGC){sub 2} was lower than that of (GGGGC){sub 4} • The frequency of (GGGGC){sub 2} in lung

  18. The association between methylenetetrahydrofolate reductase polymorphism and promoter methylation in proximal colon cancer.

    Science.gov (United States)

    Oyama, Kaeko; Kawakami, Kazuyuki; Maeda, Kazuya; Ishiguro, Kaname; Watanabe, Go

    2004-01-01

    Methylenetetrahydrofolate reductase (MTHFR) plays a critical role in folate metabolism, which is an important pathway of the methyl donor for DNA methylation. The MTHFR gene has genetic variants (C667T and A1298C), which cause reduced enzyme activity. Impaired folate metabolism by these genetic variants of MTHFR could change the methylation pattern of DNA including promoter hypermethylation, which has been frequently observed in cancer. In this study, we compared the MTHFR genotypes and haplotype to the features of colorectal cancer focusing on the promoter methylation of tumor DNA. Genomic DNA was isolated from 194 colorectal cancer tissues and subjected to MTHFR genotyping by PCR-based restriction fragment length polymorphism analysis. The MTHFR haplotype was determined by combination of C667T and A1298C genotype and classified into 2 groups, high (H-haplotype) or low (L-haplotype) enzymatic activity of MTHFR. The methylation level of tumor suppressor genes (CDKN2A, hMLH1, ARF and TIMP3) was measured by a fluorescence-based, real-time methylation specific PCR method. There was no significant association of the clinicopathological features with either C667T genotype, A1298C genotype or haplotype of MTHFR. The methylation level of CDKN2A was higher in cancer with the L-haplotype of MTHFR than in that with the H-haplotype when cancers of proximal origin were considered (p=0.029). hMLH1 methylation also tended to be higher in proximal colon cancers of MTHFR L-haplotype (p=0.059). In addition, the proximal colon cancers showing CpG island methylator phenotype (CIMP) were significantly more frequent in L-haplotype than in H-haplotype. These results suggest that the haplotype with low enzymatic activity of MTHFR is linked with promoter hypermethylation and consequently modifies the risk of CIMP(+) proximal colon cancer development in the Japanese people. The relationship between MTHFR polymorphism and DNA methylation in the Japanese is contrary to the previous results

  19. Sca-1 expression identifies stem cells in the proximal region of prostatic ducts with high capacity to reconstitute prostatic tissue

    OpenAIRE

    Patricia E Burger; Xiong, Xiaozhong; Coetzee, Sandra; Salm, Sarah N.; Moscatelli, David; Goto, Ken; Wilson, E. Lynette

    2005-01-01

    We previously showed that prostatic stem cells are concentrated in the proximal regions of prostatic ducts. We now report that these stem cells can be purified from isolated proximal duct regions by virtue of their high expression of the cell surface protein stem cell antigen 1 (Sca-1). In an in vivo prostate reconstitution assay, the purified Sca-1-expressing cell population isolated from the proximal region of ducts was more effective in generating prostatic tissue than a comparable populat...

  20. Socio-cultural proximity, daily life and shopping tourism in the Dutch–German border region

    NARCIS (Netherlands)

    Szytniewski, Bianca B.; Spierings, Bas; van der Velde, Martin

    2017-01-01

    This paper analyses feelings of socio-cultural proximity and distance with a specific focus on the tourist experience in cross-border shopping and everyday life practices in border regions. We examined shopping practices of Dutch border crossers who visit the German town Kleve in the Dutch–German

  1. INTEGRATED PROMOTION OF REGIONAL AGRICULTURAL PRODUCTS

    Directory of Open Access Journals (Sweden)

    Robert KASTNER

    2012-01-01

    Full Text Available The paper is aimed at presenting the concept and development of the rural development initiative “Genuss Region Österreich” in Austria from 2008 until the year 2010. It is based on statistical data provided by the Austrian Ministry of Agriculture, Forestry, Environment and Water Management, the initiative´s operational organisation GRM GenussRegionen Marketing GmbH and GBI Consulting, one of the evaluators of the initiative.Through the initiative installed in 2005 and during its first three years of activities, impressive results have been achieved: 113 regions have become members of the initiative by 2010; over 3.000 licenses for producers have been issued; 180 regional events with official participation of GENUSS REGION ÖSTERRICH took place in 2010; over 2.000 restaurants participated in 2010 in the seasonal promotion weeks of the initiative, over 160 retail enterprises are partners and offer regional products of the member region; over 100 touristic packages involving the member regions are available; a higher awareness of the consumers for regional products has been achieve; at the same time the awareness and proficiency, with which the producers market their products has become much higher and the cooperation with tourism, gastronomy, retail and with other regional producers has risen; quality as a key factor for sustainability and registration process of at least one product in all regions for a PDO (protected designation of origin or a PGI (protected geographical indication has been started or accomplished.

  2. Mutation affecting the proximal promoter of Endoglin as the origin of hereditary hemorrhagic telangiectasia type 1.

    Science.gov (United States)

    Albiñana, Virginia; Zafra, Ma Paz; Colau, Jorge; Zarrabeitia, Roberto; Recio-Poveda, Lucia; Olavarrieta, Leticia; Pérez-Pérez, Julián; Botella, Luisa M

    2017-02-23

    Hereditary hemorrhagic telangiectasia (HHT) is a vascular multi-organ system disorder. Its diagnostic criteria include epistaxis, telangiectases in mucocutaneous sites, arteriovenous malformations (AVMs), and familial inheritance. HHT is transmitted as an autosomal dominant condition, caused in 85% of cases by mutations in either Endoglin (ENG) or Activin receptor-like kinase (ACVRL1/ACVRL1/ALK1) genes. Pathogenic mutations have been described in exons, splice junctions and, in a few cases with ENG mutations, in the proximal promoter, which creates a new ATG start site. However, no mutations affecting transcription regulation have been described to date in HHT, and this type of mutation is rarely identified in the literature on rare diseases. Sequencing data from a family with HHT lead to single nucleotide change, c.-58G > A. The functionality and pathogenicity of this change was analyzed by in vitro mutagenesis, quantitative PCR and Gel shift assay. Student t test was used for statistical significance. A single nucleotide change, c.-58G > A, in the proximal ENG promoter co-segregated with HHT clinical features in an HHT family. This mutation was present in the proband and in 2 other symptomatic members, whereas 2 asymptomatic relatives did not harbor the mutation. Analysis of RNA from activated monocytes from the probands and the healthy brother revealed reduced ENG mRNA expression in the HHT patient (p = 0.005). Site-directed mutagenesis of the ENG promoter resulted in a three-fold decrease in luciferase activity of the mutant c.-58A allele compared to wild type (p = 0.005). Finally, gel shift assay identified a DNA-protein specific complex. The novel ENG c.-58G > A substitution in the ENG promoter co-segregates with HHT symptoms in a family and appears to affect the transcriptional regulation of the gene, resulting in reduced ENG expression. ENG c.-58G > A may therefore be a pathogenic HHT mutation leading to haploinsufficiency of

  3. Proximity and scientific collaboration in Northern European “cross-border regional innovation systems”

    DEFF Research Database (Denmark)

    Makkonen, Teemu; Williams, Allan

    2015-01-01

    A novel approach, namely cross-border regional innovation system, has been recently introduced to the literature on economic geography as a framework for studying innovation and scientific collaboration in a cross-border context. However, despite the importance of the topic for cross-border regions......, there are no existing empirical accounts comprehensively validating the concept. Here an attempt to shed some light into this “black box” is made by addressing this research gap via empirical material from Northern European cross-border regions. Specifically this is done by applying data on publications, sectoral...... and cultural statistics together with measures for accessibility and institutional and organisational similarity. These measures are linked to the varying types of proximity discussed in the literature on innovation and scientific collaboration; the impacts of proximity on the volume of cross-border scientific...

  4. Regionalization of municipal solid waste management in Japan: balancing the proximity principle with economic efficiency.

    Science.gov (United States)

    Okuda, Itaru; Thomson, Vivian E

    2007-07-01

    The proximity principle - disposing of waste close to its origin - has been a central value in municipal solid waste (MSW) management in Japan for the last 30 years and its widespread adoption has helped resolve numerous "Not in My Backyard" issues related to MSW management. However, MSW management costs have soared, in large part because of aggressive recycling efforts and because most MSW is incinerated in a country that has scarce landfill capacity. In addition, smaller, less sophisticated incinerators have been closed because of high dioxin emissions. Rising costs combined with the closure of smaller incinerators have shifted MSW management policy toward regionalization, which is the sharing of waste management facilities across municipalities. Despite the increased use of regionalized MSW facilities, the proximity principle remains the central value in Japanese MSW management. Municipal solid waste management has become increasingly regionalized in the United States, too, but different driving forces are at work in these two countries. The transition to regionalized MSW management in Japan results from strong governmental control at all levels, with the central government providing funds and policy direction and prefectures and municipalities being the primary implementing authorities. By contrast, market forces are a much stronger force with US MSW management, where local governments - with state government oversight - have primary responsibility for MSW management. We describe recent changes in Japan's MSW programs. We examine the connections between MSW facility regionalization, on the one hand, and, on the other hand, the proximity principle, coordination among local governments, central government control, and financing mechanisms.

  5. Identify fracture-critical regions inside the proximal femur using statistical parametric mapping.

    Science.gov (United States)

    Li, Wenjun; Kornak, John; Harris, Tamara; Keyak, Joyce; Li, Caixia; Lu, Ying; Cheng, Xiaoguang; Lang, Thomas

    2009-04-01

    We identified regions inside the proximal femur that are most strongly associated with hip fracture. Bone densitometry based on such fracture-critical regions showed improved power in discriminating fracture patients from controls. Hip fractures typically occur in lateral falls, with focal mechanical failure of the sub-volumes of tissue in which the applied stress exceeds the strength. In this study, we describe a new methodology to identify proximal femoral tissue elements with highest association with hip fracture. We hypothesize that bone mineral density (BMD) measured in such sub-volumes discriminates hip fracture risk better than BMD in standard anatomic regions such as the femoral neck and trochanter. We employed inter-subject registration to transform hip QCT images of 37 patients with hip fractures and 38 age-matched controls into a voxel-based statistical atlas. Within voxels, we performed t-tests between the two groups to identify the regions which differed most. We then randomly divided the 75 scans into a training set and a test set. From the training set, we derived a fracture-driven region of interest (ROI) based on association with fracture. In the test set, we measured BMD in this ROI to determine fracture discrimination efficacy using ROC analysis. Additionally, we compared the BMD distribution differences between the 29 patients with neck fractures and the 8 patients with trochanteric fractures. By evaluating fracture discrimination power based on ROC analysis, the fracture-driven ROI had an AUC (area under curve) of 0.92, while anatomic ROIs (including the entire proximal femur, the femoral neck, trochanter and their cortical and trabecular compartments) had AUC values between 0.78 and 0.87. We also observed that the neck fracture patients had lower BMD (p=0.014) in a small region near the femoral neck and the femoral head, and patients with trochanteric fractures had lower BMD in trochanteric regions such as in the internal calcar septum (p=0

  6. ZONAB promotes proliferation and represses differentiation of proximal tubule epithelial cells.

    Science.gov (United States)

    Lima, Wânia R; Parreira, Kleber S; Devuyst, Olivier; Caplanusi, Adrian; N'kuli, Francisca; Marien, Benoit; Van Der Smissen, Patrick; Alves, Pedro M S; Verroust, Pierre; Christensen, Erik I; Terzi, Fabiola; Matter, Karl; Balda, Maria S; Pierreux, Christophe E; Courtoy, Pierre J

    2010-03-01

    Epithelial polarization modulates gene expression. The transcription factor zonula occludens 1 (ZO-1)-associated nucleic acid binding protein (ZONAB) can shuttle between tight junctions and nuclei, promoting cell proliferation and expression of cyclin D1 and proliferating cell nuclear antigen (PCNA), but whether it also represses epithelial differentiation is unknown. Here, during mouse kidney ontogeny and polarization of proximal tubular cells (OK cells), ZONAB and PCNA levels decreased in parallel and inversely correlated with increasing apical differentiation, reflected by expression of megalin/cubilin, maturation of the brush border, and extension of the primary cilium. Conversely, ZONAB reexpression and loss of apical differentiation markers provided a signature for renal clear cell carcinoma. In confluent OK cells, ZONAB overexpression increased proliferation and PCNA while repressing megalin/cubilin expression and impairing differentiation of the brush border and primary cilium. Reporter and chromatin immunoprecipitation assays demonstrated that megalin and cubilin are ZONAB target genes. Sparsely plated OK cells formed small islands composed of distinct populations: Cells on the periphery, which lacked external tight junctions, strongly expressed nuclear ZONAB, proliferated, and failed to differentiate; central cells, surrounded by continuous junctions, lost nuclear ZONAB, stopped proliferating, and engaged in apical differentiation. Taken together, these data suggest that ZONAB is an important component of the mechanisms that sense epithelial density and participates in the complex transcriptional networks that regulate the switch between proliferation and differentiation.

  7. DNAH11 Localization in the Proximal Region of Respiratory Cilia Defines Distinct Outer Dynein Arm Complexes.

    Science.gov (United States)

    Dougherty, Gerard W; Loges, Niki T; Klinkenbusch, Judith A; Olbrich, Heike; Pennekamp, Petra; Menchen, Tabea; Raidt, Johanna; Wallmeier, Julia; Werner, Claudius; Westermann, Cordula; Ruckert, Christian; Mirra, Virginia; Hjeij, Rim; Memari, Yasin; Durbin, Richard; Kolb-Kokocinski, Anja; Praveen, Kavita; Kashef, Mohammad A; Kashef, Sara; Eghtedari, Fardin; Häffner, Karsten; Valmari, Pekka; Baktai, György; Aviram, Micha; Bentur, Lea; Amirav, Israel; Davis, Erica E; Katsanis, Nicholas; Brueckner, Martina; Shaposhnykov, Artem; Pigino, Gaia; Dworniczak, Bernd; Omran, Heymut

    2016-08-01

    Primary ciliary dyskinesia (PCD) is a recessively inherited disease that leads to chronic respiratory disorders owing to impaired mucociliary clearance. Conventional transmission electron microscopy (TEM) is a diagnostic standard to identify ultrastructural defects in respiratory cilia but is not useful in approximately 30% of PCD cases, which have normal ciliary ultrastructure. DNAH11 mutations are a common cause of PCD with normal ciliary ultrastructure and hyperkinetic ciliary beating, but its pathophysiology remains poorly understood. We therefore characterized DNAH11 in human respiratory cilia by immunofluorescence microscopy (IFM) in the context of PCD. We used whole-exome and targeted next-generation sequence analysis as well as Sanger sequencing to identify and confirm eight novel loss-of-function DNAH11 mutations. We designed and validated a monoclonal antibody specific to DNAH11 and performed high-resolution IFM of both control and PCD-affected human respiratory cells, as well as samples from green fluorescent protein (GFP)-left-right dynein mice, to determine the ciliary localization of DNAH11. IFM analysis demonstrated native DNAH11 localization in only the proximal region of wild-type human respiratory cilia and loss of DNAH11 in individuals with PCD with certain loss-of-function DNAH11 mutations. GFP-left-right dynein mice confirmed proximal DNAH11 localization in tracheal cilia. DNAH11 retained proximal localization in respiratory cilia of individuals with PCD with distinct ultrastructural defects, such as the absence of outer dynein arms (ODAs). TEM tomography detected a partial reduction of ODAs in DNAH11-deficient cilia. DNAH11 mutations result in a subtle ODA defect in only the proximal region of respiratory cilia, which is detectable by IFM and TEM tomography.

  8. Microbial diversity in an anaerobic digester with biogeographical proximity to geothermally active region.

    Science.gov (United States)

    Mahajan, Rishi; Nikitina, Anna; Nozhevnikova, Alla; Goel, Gunjan

    2016-11-01

    Anaerobic digestion of agricultural biomass or wastes can offer renewable energy, to help meet the rise in energy demands. The performance of an anaerobic digester considerably depends upon the complex interactions between bacterial and archaeal microbiome, which is greatly influenced by environmental factors. In the present study, we evaluate a microbial community of digester located at two different geographical locations, to understand whether the biogeographical proximity of a digester to a geothermally active region has any influence on microbial composition. The comparative microbial community profiling, highlights coexistence of specific bacterial and archaeal representatives (especially, Prosthecochloris sp., Conexibacter sp., Crenarchaeota isolate (Caldivirga sp.), Metallosphaera sp., Pyrobaculum sp. and Acidianus sp.) in a digester with close proximity to geothermally active region (Site I) and their absence in a digester located far-off from geothermally active region (Site II). A Sörensen's index of similarity of 83.33% and 66.66% for bacterial and archaeal community was observed in both the reactors, respectively.

  9. Comparison between two experimental protocols to promote osteoporosis in the maxilla and proximal tibia of female rats

    Directory of Open Access Journals (Sweden)

    Teófilo Juliana Mazzonetto

    2003-01-01

    Full Text Available The effects of two experimental protocols (ovariectomy associated or not with a low calcium diet used to promote osteoporosis in the rat maxilla and proximal tibia were compared 5 and 11 weeks after surgery. Female Wistar rats were ovariectomized or sham-operated. Half of the ovariectomized rats were fed a low Ca++ diet (ovx* and the remaining ovariectomized (ovx and sham animals received a standard chow. At sacrifice, the proximal metaphysis was excised from the tibia and the molars were extracted from the hemi-maxilla. Dry (60°C overnight and ash (700°C/14 h weights were measured and the ashes were used for Ca++ measurement by means of a colorimetric method. After 5 weeks, ovx caused no alteration while ovx* decreased proximal metaphysis (17% and maxilla (35% bone mass. After 11 weeks, ovx caused a 14% bone mass reduction in the proximal metaphysis but not in the maxilla, while ovx* caused a comparable bone mass reduction (30% in both bone segments. Calcium concentration was not altered in any experimental condition. The results show that estrogen deficiency is insufficient to cause maxillary osteoporosis in rats over an 11-week period and a long-term ovariectomy is needed to exert deleterious effect on proximal metaphysis bone mass. When a low Ca++ diet is associated with estrogen deficiency, however, a relatively precocious harmful effect is observed, twice as pronounced in the maxilla than in the proximal metaphysis. On a long-term basis, ovariectomy associated with a low Ca++ diet seems to be equally injurious to both proximal metaphysis and maxilla.

  10. Far infrared radiation promotes rabbit renal proximal tubule cell proliferation and functional characteristics, and protects against cisplatin-induced nephrotoxicity.

    Science.gov (United States)

    Chiang, I-Ni; Pu, Yeong-Shiau; Huang, Chao-Yuan; Young, Tai-Horng

    2017-01-01

    Far infrared radiation, a subdivision of the electromagnetic spectrum, is beneficial for long-term tissue healing, anti-inflammatory effects, growth promotion, sleep modulation, acceleration of microcirculation, and pain relief. We investigated if far infrared radiation is beneficial for renal proximal tubule cell cultivation and renal tissue engineering. We observed the effects of far infrared radiation on renal proximal tubules cells, including its effects on cell proliferation, gene and protein expression, and viability. We also examined the protective effects of far infrared radiation against cisplatin, a nephrotoxic agent, using the human proximal tubule cell line HK-2. We found that daily exposure to far infrared radiation for 30 min significantly increased rabbit renal proximal tubule cell proliferation in vitro, as assessed by MTT assay. Far infrared radiation was not only beneficial to renal proximal tubule cell proliferation, it also increased the expression of ATPase Na+/K+ subunit alpha 1 and glucose transporter 1, as determined by western blotting. Using quantitative polymerase chain reaction, we found that far infrared radiation enhanced CDK5R1, GNAS, NPPB, and TEK expression. In the proximal tubule cell line HK-2, far infrared radiation protected against cisplatin-mediated nephrotoxicity by reducing apoptosis. Renal proximal tubule cell cultivation with far infrared radiation exposure resulted in better cell proliferation, significantly higher ATPase Na+/K+ subunit alpha 1 and glucose transporter 1 expression, and significantly enhanced expression of CDK5R1, GNAS, NPPB, and TEK. These results suggest that far infrared radiation improves cell proliferation and differentiation. In HK-2 cells, far infrared radiation mediated protective effects against cisplatin-induced nephrotoxicity by reducing apoptosis, as indicated by flow cytometry and caspase-3 assay.

  11. Polymorphisms of beta-lactoglobulin promoter region in three Sicilian goat breeds.

    Science.gov (United States)

    Sardina, M T; Rosa, A J M; Davoli, R; Braglia, S; Portolano, B

    2012-03-01

    Several beta-lactoglobulin (BLG) polymorphisms have been described within the proximal promoter region and coding region of the caprine gene, although no genetic variants affecting the protein amino acid composition and/or expression level have been characterized so far. Binding sites for several transcription factors (TFs) are present in the BLG promoter region. The aims of this work were to sequence the full-length promoter region of three Sicilian goat breeds in order to identify polymorphisms, analyze the identified haplotypes, search for differences between breeds for the presence of polymorphisms in this gene region, search for putative TFs binding sites, and check if polymorphisms lay within the identified TFs binding sites. The promoter region of BLG gene in Sicilian goat breeds showed high level of polymorphism due to the presence of 36 single nucleotide polymorphisms (SNPs). Association between polymorphic sites was computed within the whole sample analyzed and 18 haplotypes were inferred. Binding sites for three milk protein binding factors (MPBFs) and four nuclear factor-I (NF-I) were found within BLG promoter region based on the ovine sequence. The identification of some SNPs within TFs binding sites allowed hypothesizing the loss of TFs. Further studies are in progress to evaluate the effect of these mutations on binding affinity of TFs, the functional interaction of the TFs with the goat BLG promoter, and the relationship of the polymorphisms with BLG gene expression and milk production and composition.

  12. Brain region's relative proximity as marker for Alzheimer's disease based on structural MRI

    DEFF Research Database (Denmark)

    Erleben, Lene Lillemark; Sørensen, Lauge Emil; Pai, Akshay Sadananda Uppinakudru

    2014-01-01

    brain structures like hippocampus, this paper investigates the relationship and proximity between regions in the brain and uses this information as a novel way of classifying normal control (NC), mild cognitive impaired (MCI), and AD subjects.METHODS:A longitudinal cohort of 528 subjects (170 NC, 240......BACKGROUND:Alzheimer's disease (AD) is a progressive, incurable neurodegenerative disease and the most common type of dementia. It cannot be prevented, cured or drastically slowed, even though AD research has increased in the past 5-10 years. Instead of focusing on the brain volume or on the single...... MCI, and 114 AD) from ADNI at baseline and month 12 was studied. We investigated a marker based on Procrustes aligned center of masses and the percentile surface connectivity between regions. These markers were classified using a linear discriminant analysis in a cross validation setting and compared...

  13. Complete dissociation of the HIV-1 gp41 ectodomain and membrane proximal regions upon phospholipid binding

    Energy Technology Data Exchange (ETDEWEB)

    Roche, Julien; Louis, John M.; Aniana, Annie [National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Chemical Physics (United States); Ghirlando, Rodolfo [National Institutes of Health, Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases (United States); Bax, Ad, E-mail: bax@nih.gov [National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Chemical Physics (United States)

    2015-04-15

    The envelope glycoprotein gp41 mediates the process of membrane fusion that enables entry of the HIV-1 virus into the host cell. Strong lipid affinity of the ectodomain suggests that its heptad repeat regions play an active role in destabilizing membranes by directly binding to the lipid bilayers and thereby lowering the free-energy barrier for membrane fusion. In such a model, immediately following the shedding of gp120, the N-heptad and C-heptad helices dissociate and melt into the host cell and viral membranes, respectively, pulling the destabilized membranes into juxtaposition, ready for fusion. Post-fusion, reaching the final 6-helix bundle (6HB) conformation then involves competition between intermolecular interactions needed for formation of the symmetric 6HB trimer and the membrane affinity of gp41’s ectodomain, including its membrane-proximal regions. Our solution NMR study of the structural and dynamic properties of three constructs containing the ectodomain of gp41 with and without its membrane-proximal regions suggests that these segments do not form inter-helical interactions until the very late steps of the fusion process. Interactions between the polar termini of the heptad regions, which are not associating with the lipid surface, therefore may constitute the main driving force initiating formation of the final post-fusion states. The absence of significant intermolecular ectodomain interactions in the presence of dodecyl phosphocholine highlights the importance of trimerization of gp41’s transmembrane helix to prevent complete dissociation of the trimer during the course of fusion.

  14. An Alphavirus E2 Membrane-Proximal Domain Promotes Envelope Protein Lateral Interactions and Virus Budding

    Directory of Open Access Journals (Sweden)

    Emily A. Byrd

    2017-11-01

    Full Text Available Alphaviruses are members of a group of small enveloped RNA viruses that includes important human pathogens such as Chikungunya virus and the equine encephalitis viruses. The virus membrane is covered by a lattice composed of 80 spikes, each a trimer of heterodimers of the E2 and E1 transmembrane proteins. During virus endocytic entry, the E1 glycoprotein mediates the low-pH-dependent fusion of the virus membrane with the endosome membrane, thus initiating virus infection. While much is known about E1 structural rearrangements during membrane fusion, it is unclear how the E1/E2 dimer dissociates, a step required for the fusion reaction. A recent Alphavirus cryo-electron microscopy reconstruction revealed a previously unidentified D subdomain in the E2 ectodomain, close to the virus membrane. A loop within this region, here referred to as the D-loop, contains two highly conserved histidines, H348 and H352, which were hypothesized to play a role in dimer dissociation. We generated Semliki Forest virus mutants containing the single and double alanine substitutions H348A, H352A, and H348/352A. The three D-loop mutations caused a reduction in virus growth ranging from 1.6 to 2 log but did not significantly affect structural protein biosynthesis or transport, dimer stability, virus fusion, or specific infectivity. Instead, growth reduction was due to inhibition of a late stage of virus assembly at the plasma membrane. The virus particles that are produced show reduced thermostability compared to the wild type. We propose the E2 D-loop as a key region in establishing the E1-E2 contacts that drive glycoprotein lattice formation and promote Alphavirus budding from the plasma membrane.

  15. Catchment model regionalization approach based on spatial proximity: Does a neighbor catchment-based rainfall input strengthen the method?

    Directory of Open Access Journals (Sweden)

    Gilles Drogue

    2016-12-01

    New hydrological insights for the region: Results show that when streamflow is known at the outlet of a catchment, optimal rainfall input for a lumped catchment model is mostly computed with a subset of raingages. When streamflow is unkown at the outlet of a catchment, a regionalisation approach of model parameter values based on spatial proximity is not able to take advantage of a neighbor-catchment based knowledge of optimal rainfall input. This report encourages to search for a catchment model regionalization approach based on spatial proximity which makes no explicit use of measured rainfall to estimate streamflow at an ungauged location.

  16. Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity

    Directory of Open Access Journals (Sweden)

    Todd Bradley

    2016-10-01

    Full Text Available Most HIV-1 vaccines elicit neutralizing antibodies that are active against highly sensitive (tier-1 viruses or rare cases of vaccine-matched neutralization-resistant (tier-2 viruses, but no vaccine has induced antibodies that can broadly neutralize heterologous tier-2 viruses. In this study, we isolated antibodies from an HIV-1-infected individual that targeted the gp41 membrane-proximal external region (MPER that may have selected single-residue changes in viral variants in the MPER that resulted in neutralization sensitivity to antibodies targeting distal epitopes on the HIV-1 Env. Similarly, a single change in the MPER in a second virus from another infected-individual also conferred enhanced neutralization sensitivity. These gp41 single-residue changes thus transformed tier-2 viruses into tier-1 viruses that were sensitive to vaccine-elicited tier-1 neutralizing antibodies. These data demonstrate that Env amino acid changes within the MPER bnAb epitope of naturally-selected escape viruses can increase neutralization sensitivity to multiple types of neutralizing antibodies, and underscore the critical importance of the MPER for maintaining the integrity of the tier-2 HIV-1 trimer.

  17. Promoting Metapragmatic Development through Assessment in the Zone of Proximal Development

    Science.gov (United States)

    van Compernolle, Remi A.; Kinginger, Celeste

    2013-01-01

    The assessment of second language (L2) pragmatic competence typically involves questionnaires, such as discourse completion tasks. This article describes a novel approach to using questionnaires to assess L2 metapragmatic capacities while simultaneously promoting their development: engaging learners in cooperative interaction as they complete the…

  18. [Health-Promoting Schools Regional Initiative of the Americas].

    Science.gov (United States)

    Ippolito-Shepherd, Josefa; Cerqueira, Maria Teresa; Ortega, Diana Patricia

    2005-01-01

    In Latin America, comprehensive health promotion programmes and activities are being implemented in the school setting, which take into account the conceptual framework of the Health-Promoting Schools Regional Initiative of the Pan American Health Organization, Regional office of the World Health Organization (PAHO/WHO). These programmes help to strengthen the working relationships between the health and education sectors. The Health-Promoting Schools Regional Initiative, officially launched by PAHO/WHO in 1995, aims to form future generations to have the knowledge, abilities, and skills necessary for promoting and caring for their health and that of their family and community, as well as to create and maintain healthy environments and communities. The Initiative focuses on three main components: comprehensive health education, the creation and maintenance of healthy physical and psychosocial environments, and the access to health and nutrition services, mental health, and active life. In 2001, PAHO conducted a survey in 19 Latin American countries to assess the status and trends of Health-Promoting Schools in the Region, for the appropriate regional, subregional, and national planning of pertinent health promotion and health education programmes and activities. The results of this survey provided information about policies and national plans, multisectoral coordination mechanisms for the support of health promotion in the school settings, the formation and participation in national and international networks of Health-Promoting Schools and about the level of dissemination of the strategy. For the successful development of Health-Promoting Schools is essential to involve the society as a whole, in order to mobilise human resources and materials necessary for implementing health promotion in the school settings. Thus, the constitution and consolidation of networks has been a facilitating mechanism for the exchange of ideas, resources and experiences to strengthen

  19. Magnetic resonance study on the anatomical relationship between the posterior proximal region of the tibia and the popliteal artery ☆

    Directory of Open Access Journals (Sweden)

    Rogério Franco de Araujo Goes

    2015-08-01

    Full Text Available ABSTRACTOBJECTIVE: To analyze and describe the distance from the popliteal artery to three specific areas of the proximal region of the tibia, with the knee extended, by means of magnetic resonance. METHODS: Images of 100 knees of patients who underwent magnetic resonance examinations were analyzed. The location of the popliteal artery was measured in three different areas of the posterior proximal region of the tibia. The first measurement was made at the level of the knee joint (tibial plateau. The second was 9 mm distally to the tibial plateau. The third was at the level of the anterior tuberosity of the tibia (ATT. RESULTS: The distances between the popliteal artery and the tibial plateau and ATT region were significantly greater in males than in females. The distances between the popliteal artery and the regions 9 mm distally to the tibial plateau and the ATT were significantly greater in the age group over 36 years than in the group ≤36 years. CONCLUSION: Knowledge of the anatomical position of the popliteal artery, as demonstrated through magnetic resonance studies, is of great relevance in planning surgical procedures that involve the knee joint. In this manner, devastating iatrogenic injuries can be avoided, particularly in regions that are proximal to the tibial plateau and in young patients.

  20. Identification and annotation of promoter regions in microbial ...

    Indian Academy of Sciences (India)

    2007-06-15

    Jun 15, 2007 ... Analysis of various predicted structural properties of promoter regions in prokaryotic as well as eukaryotic genomes had earlier indicated that they have several common features, such as lower stability, higher curvature and less bendability, when compared with their neighboring regions. Based on the ...

  1. the principles of diversity and geographical proximity in an industrial ecosystem: social network analysis in the Toluca-Lerma region

    Directory of Open Access Journals (Sweden)

    Manuel Alexis Vazquez Zacarias

    2015-07-01

    Full Text Available Industrial ecology allows the traditional model of industrial activity, where individual manufacturing process that takes raw materials in order to generate products, to be transformed into a more comprehensive model of a regional economy named industrial ecosystem. This ecosystem functions through industrial symbiosis alliances formed by firms that cooperate through the exchange of residues in order to use them as inputs to transform them into valuable products. Moreover, the principles of geographical proximity and diversity of the firms have been found in successful ecosystems in developed countries. This study contributes empirically by using social network analysis (SNA methods to explore, the presence of these two principles in an industrial ecosystem in the Toluca-Lerma region in Mexico, consisting of 30 firms that have industrial symbiosis alliances. We conclude that in the context of developing countries, the symbiotic exchanges may not be fully explained with the principles of geographical proximity and diversity.

  2. Sequence and Phylogenetic Analysis of the Untranslated Promoter Regions for HLA Class I Genes.

    Science.gov (United States)

    Ramsuran, Veron; Hernández-Sanchez, Pedro G; O'hUigin, Colm; Sharma, Gaurav; Spence, Niamh; Augusto, Danillo G; Gao, Xiaojiang; García-Sepúlveda, Christian A; Kaur, Gurvinder; Mehra, Narinder K; Carrington, Mary

    2017-03-15

    Polymorphisms located within the MHC have been linked to many disease outcomes by mechanisms not yet fully understood in most cases. Variants located within untranslated regions of HLA genes are involved in allele-specific expression and may therefore underlie some of these disease associations. We determined sequences extending nearly 2 kb upstream of the transcription start site for 68 alleles from 57 major lineages of classical HLA class I genes. The nucleotide diversity within this promoter segment roughly follows that seen within the coding regions, with HLA-B showing the highest (∼1.9%), followed by HLA-A (∼1.8%), and HLA-C showing the lowest diversity (∼0.9%). Despite its greater diversity, HLA-B mRNA expression levels determined in 178 European Americans do not vary in an allele- or lineage-specific manner, unlike the differential expression levels of HLA-A or HLA-C reported previously. Close proximity of promoter sequences in phylogenetic trees is roughly reflected by similarity of expression pattern for most HLA-A and -C loci. Although promoter sequence divergence might impact promoter activity, we observed no clear link between the phylogenetic structures as represented by pairwise nucleotide differences in the promoter regions with estimated differences in mRNA expression levels for the classical class I loci. Further, no pair of class I loci showed coordinated expression levels, suggesting that distinct mechanisms across loci determine their expression level under nonstimulated conditions. These data serve as a foundation for more in-depth analysis of the functional consequences of promoter region variation within the classical HLA class I loci. Copyright © 2017 by The American Association of Immunologists, Inc.

  3. A Leader Intron of a Soybean Elongation Factor 1A (eEF1A Gene Interacts with Proximal Promoter Elements to Regulate Gene Expression in Synthetic Promoters.

    Directory of Open Access Journals (Sweden)

    Ning Zhang

    Full Text Available Introns, especially the first intron in the 5' untranslated region (5'UTR, can significantly impact gene expression via intron-mediated enhancement (IME. In this study, we demonstrate the leader intron of a soybean elongation factor 1A (eEF1A gene (GmScreamM8 was essential for the high activity of the native promoter. Furthermore, the interaction of the GmScreamM8 leader intron with regulatory element sequences from several soybean eEF1A promoters was studied using synthetic promoters, which consisted of element tetramers upstream of a core promoter used to regulate a green fluorescent protein (gfp reporter gene. Element tetramers, placed upstream of a GmScreamM8 core promoter, showed very high activity using both transient expression in lima bean cotyledons and stable expression in soybean hairy roots, only if the native leader intron was included, suggesting an interaction between intronic sequences and promoter elements. Partial deletions of the leader intron showed that a 222 bp intronic sequence significantly contributed to very high levels of GFP expression. Generation of synthetic intron variants with a monomeric or trimeric repeat of the 222 bp intronic sequence, yielded almost two-fold higher expression compared to the original intron, while partial deletion of the 222 bp intronic repeated sequence significantly decreased gene expression, indicating that this intronic sequence was essential for the intron-element interaction enhancement.

  4. Identification and annotation of promoter regions in microbial ...

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    2007-06-15

    Jun 15, 2007 ... Werner 1999; Ohler and Niemann 2001). Most of them. Identification and annotation of promoter regions in microbial genome sequences on the basis of DNA stability. VETRISELVI RANGANNAN and MANJU BANSAL*. Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India.

  5. Proximity to mosquito breeding habitat and Ross River virus risk in the Peel region of Western Australia.

    Science.gov (United States)

    Jardine, Andrew; Neville, Peter J; Lindsay, Michael D A

    2015-02-01

    It is intuitive that vector-borne disease exposure risk is related to proximity to sources of vector breeding, but this aspect rarely receives empirical testing. The population of Western Australia (WA) is increasing rapidly, with many new residential developments proposed in close proximity to mosquito breeding habitat. However, potential mosquito-borne disease risks for future residents are given little consideration by planning authorities. The Peel region is one of the fastest growing regions in WA and regularly experiences a large number of cases of the mosquito-borne Ross River virus (RRV) disease with epidemics occuring in the region every few years. A spatial analysis of RRV disease data in the Peel region was undertaken to determine the risk associated with proximity to a mosquito breeding habitat. Geographic Information Systems (GIS) software was used to create buffers between 1 and 6 km from the breeding habitat. The number of cases per 1000 dwellings in each buffer was calculated between 2002/03 to 2011/12 for years with >100 cases across all buffers (n=5) in addition to the cumulative rate over the entire period in each buffer. Residents living within 1 km of a mosquito breeding habitat had a significantly higher rate of RRV disease compared to the background rate across the Peel region in all individual years investigated. The cumulative data over the 10-year study period showed that residents in the 1- and 2-km buffers had a significantly higher rate, whereas those living between 3 and 6 km away did not. This study demonstrates an increased mosquito-borne disease risk associated with living in close proximity to a mosquito breeding habitat in a rapidly expanding region of WA and highlights the importance of considering mosquito-borne disease risks when planning authorities assess new residential development applications. Known mosquito breeding wetlands should be incorporated into land use planning scheme maps to ensure that they are accurately

  6. Molecular characterization of two proximal deletion breakpoint regions in both Prader-Willi and Angelman syndrome patients

    Energy Technology Data Exchange (ETDEWEB)

    Christian, S.L.; Huang, B.; Ledbetter, D.H. [National Institutes of Health, Bethesda, MD (United States)] [and others

    1995-07-01

    Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct mental retardation syndromes caused by paternal and maternal deficiencies, respectively, in chromosome 15q11{minus}q13. Approximately 70% of these patients have a large deletion of {approximately}4 Mb extending from D15S9 (ML34) through D15S12 (IR10A). To further characterize the deletion breakpoints proximal to D15S9, three new polymorphic microsatellite markers were developed that showed observed heterozygosities of 60%-87%. D15S541 and D15S542 were isolated for YAC A124A3 containing the D15S18 (IR39) locus. D15S543 was isolated from a cosmid cloned from the proximal right end of YAC 254B5 containing the D15S9 (ML34) locus. Gene-centromere mapping of these markers, using a panel of ovarian teratomas of known meiotic origin, extended the genetic map of chromosome 15 by 2-3 cM toward the centromere. Analysis of the more proximal S541/S542 markers on 53 Prader-Willi and 33 Angelman deletion patients indicated two classes of patients: 44% (35/80) of the informative patients were deleted for these markers (class I), while 56% (45/80) were not deleted (class II), with no difference between PWS and AS. In contrast, D15S543 was deleted in all informative patients (13/48) or showed the presence of a single allele (in 35/48 patients), suggesting that this marker is deleted in the majority of PWS and AS cases. These results confirm the presence of two common proximal deletion breakpoint regions in both Prader-Willi and Angelman syndromes and are consistent with the same deletion mechanism being responsible for paternal and maternal deletions. One breakpoint region lies between D15S541/S542 and D15S543, with an additional breakpoint region being proximal to D15S541/S542. 46 refs., 2 figs., 3 tabs.

  7. A influência da proximidade tecnológica e geográfica sobre a inovação regional no Brasil The influence of the technological proximity and the geographical proximity on Brazilian regional innovation

    Directory of Open Access Journals (Sweden)

    Eduardo Gonçalves

    2011-04-01

    Full Text Available O objetivo deste trabalho é verificar a influência da proximidade geográfica e da proximidade tecnológica sobre a inovação regional no Brasil, medida por depósitos de patentes no período 1999-2001 para mesorregiões geográficas. Para tanto, utilizaram-se técnicas de Análise Exploratória de Dados Espaciais (AEDE e de econometria espacial. Os dados de patentes foram organizados em quatro clusters tecnológicos segundo critérios de proximidade cognitiva, como biofarmacêutico, desenvolvimento de novos materiais, bens mecânicos e de consumo e tecnologias eletroeletrônicas, revelando um padrão de concentração da atividade tecnológica em poucas mesorregiões brasileiras. Além disso, foi calculada a medida de proximidade tecnológica de Jaffe para ponderar a vizinhança geográfica pelo grau de similaridade tecnológica das mesorregiões. Os resultados confirmam a hipótese de transbordamentos de conhecimento mediados tecnológica e geograficamente.The aim of this paper is to determine the influence of technological proximity and geographical proximity on Brazilian regional innovation, measured by patent applications over the period 1999-2001 for Brazilian geographical mesoregions. First, the paper undertakes an Exploratory Spatial Data Analysis (ESDA and then uses spatial econometric techniques. According with procedures based on cognitive proximity the patent data are organized into four technological clusters such as chemical and bio-pharmaceutical, new materials, mechanical and process technologies and electrical and electronic technologies. The four aforementioned clusters exhibit a concentrated regional pattern of technological activity over few Brazilian mesoregions. Moreover, the paper uses a Jaffe's measure of technological distance in order to construct a matrix in which the technological similarity is weighted by the geographical proximity. The results corroborate the hypothesis of geographically and technologically

  8. Structural and functional characterization of EIAV gp45 fusion peptide proximal region and asparagine-rich layer

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Liangwei; Du, Jiansen [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China); Wang, Xuefeng; Zhou, Jianhua; Wang, Xiaojun [State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Liu, Xinqi, E-mail: liu2008@nankai.edu.cn [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China)

    2016-04-15

    Equine infectious anaemia virus (EIAV) and human immunodeficiency virus (HIV) are members of the lentiviral genus. Similar to HIV gp41, EIAV gp45 is a fusogenic protein that mediates fusion between the viral particle and the host cell membrane. The crystal structure of gp45 reported reveals a different conformation in the here that includes the fusion peptide proximal region (FPPR) and neighboring asparagine-rich layer compared with previous HIV-1 gp41 structures. A complicated hydrogen-bond network containing a cluster of solvent molecules appears to be critical for the stability of the gp45 helical bundle. Interestingly, viral replication was relatively unaffected by site-directed mutagenesis of EIAV, in striking contrast to that of HIV-1. Based on these observations, we speculate that EIAV is more adaptable to emergent mutations, which might be important for the evolution of EIAV as a quasi-species, and could potentially contribute to the success of the EIAV vaccine. - Highlights: • The crystal structure of EIAV gp45 was determined. • The fusion peptide proximal region adopts a novel conformation different to HIV-1. • The asparagine-rich layer includes an extensive hydrogen-bond network. • These regions of EIAV are highly tolerant to mutations. • The results provide insight into the mechanism of gp41/gp45-mediated membrane fusion.

  9. An Ebox element in the proximal Gata4 promoter is required for Gata4 expression in vivo.

    Directory of Open Access Journals (Sweden)

    Alain Boulende Sab

    Full Text Available GATA4 is an essential transcription factor required for the development and function of multiple tissues, including a major role in gonadogenesis. Despite its crucial role, the molecular mechanisms that regulate Gata4 expression in vivo remain poorly understood. We recently found that the Gata4 gene is expressed as multiple transcripts with distinct 5' origins. These co-expressed alternative transcripts are generated by different non-coding first exons with transcripts E1a and E1b being the most prominent. Moreover, we previously showed that an Ebox element, located in Gata4 5' flanking sequences upstream of exon 1a, is important for the promoter activity of these sequences in cell lines. To confirm the importance of this element in vivo, we generated and characterized Gata4 Ebox knockout mice. Quantitative PCR analyses realized on gonads, heart and liver at three developmental stages (embryonic, pre-pubertal and adult revealed that the Ebox mutation leads to a robust and specific decrease (up to 89% of Gata4 E1a transcript expression in all tissues and stages examined. However, a detailed characterization of the gonads revealed normal morphology and GATA4 protein levels in these mutants. Our qPCR data further indicate that this outcome is most likely due to the presence of Gata4 E1b mRNA, whose expression levels were not decreased by the Ebox mutation. In conclusion, our work clearly confirms the importance of the proximal Ebox element and suggests that adequate GATA4 protein expression is likely protected by a compensation mechanism between Gata4 E1a and E1b transcripts operating at the translational level.

  10. Functional characterization of the HOXB13 promoter region.

    Science.gov (United States)

    Cross, Deanna S; Burmester, J K

    2008-01-01

    Homeobox (HOX) genes are crucial regulators of cell growth and differentiation. These genes initiate and control gene expression cascades that drive development. More recently, the absent or aberrant expression of HOX genes has been implicated in cancer development. Despite the observance of these expression changes, the regulation of the HOX genes in adult tissues and how these genes become deregulated in cancerous tissues still needs much investigation. We characterized the promoter region of the HOXB13 gene. A 3 kb region upstream of the HOXB13 gene, which included the 5'UTR, increased reporter gene expression in LNCaP cells by approximately 99 fold over the promoterless control construct. A highly conserved 179 base pair fragment containing only the 5'UTR of the HOXB13 gene constituted a minimal promoter in the LNCaP cell line. Strong promoter activity was seen in the presence or absence of testosterone, although testosterone exposure did decrease expression in LNCaP cells by 50%. In an androgen insensitive cell line Du145, no sensitivity to testosterone was detected and a consistent low basal level of expression was observed. Since HOXB13 expression is highly tissue specific, we investigated the ability of the promoter to drive expression in tissues other than prostate. We observed highest expression in LNCaP cells with low levels of expression in lung, retinoblastoma, and colon cancer cells and higher expression in MCF7 breast cancer cells.

  11. Lhx1 in the proximal region of the optic vesicle permits neural retina development in the chicken

    Directory of Open Access Journals (Sweden)

    Takumi Kawaue

    2012-08-01

    How the eye forms has been one of the fundamental issues in developmental biology. The retinal anlage first appears as the optic vesicle (OV evaginating from the forebrain. Subsequently, its distal portion invaginates to form the two-walled optic cup, which develops into the outer pigmented and inner neurosensory layers of the retina. Recent work has shown that this optic-cup morphogenesis proceeds as a self-organizing activity without any extrinsic molecules. However, intrinsic factors that regulate this process have not been elucidated. Here we show that a LIM-homeobox gene, Lhx1, normally expressed in the proximal region of the nascent OV, induces a second neurosensory retina formation from the outer pigmented retina when overexpressed in the chicken OV. Lhx2, another LIM-homeobox gene supposed to be involved in early OV formation, could not substitute this function of Lhx1, while Lhx5, closely related to Lhx1, could replace it. Conversely, knockdown of Lhx1 expression by RNA interference resulted in the formation of a small or pigmented vesicle. These results suggest that the proximal region demarcated by Lhx1 expression permits OV development, eventually dividing the two retinal domains.

  12. Conserved residues within the HIV-1 Vpu transmembrane-proximal hinge region modulate BST2 binding and antagonism.

    Science.gov (United States)

    Lukhele, Sabelo; Cohen, Éric A

    2017-03-14

    BST2 inhibits HIV-1 release by tethering nascent virions to the surface of infected cells. HIV-1 Vpu overcomes this restriction by removing BST2 from viral budding sites via BST2 intracellular trapping and sequestration, surface downregulation and/or displacement mechanisms. Vpu is composed of a short luminal tail, a transmembrane domain (TMD) and a cytoplasmic hinge region that is followed by two helices. BST2 counteraction relies on the ability of Vpu to physically bind BST2 through TMD interactions and recruit the clathrin-dependent trafficking machinery via a canonical acidic di-leucine signalling motif within the helix-2 of Vpu. The highly conserved Vpu transmembrane-proximal hinge region encompasses residues that resemble an acidic leucine-based trafficking motif, whose functional roles are currently ill-defined. In this study, we investigated the contribution of these residues towards Vpu-mediated BST2 antagonism. We show that while these conserved residues have no intrinsic activity on the cellular distribution of Vpu in the absence of BST2, they regulate the ability of Vpu to bind to BST2 and, consequently, govern both BST2-dependent trafficking properties of the protein as well as its co-localization with BST2. Moreover, these residues, particularly a glutamic acid residue positioned immediately following the TMD, are a determinant not only for efficient targeting of BST2, but also binding and degradation of CD4, another host membrane protein targeted by Vpu. Mechanistically, our data are consistent with a role of these residues in the maintenance of the Vpu TMD conformational configuration such that interactions with membrane-associated host targets are favoured. Altogether, this work demonstrates an important regulatory role of the transmembrane-proximal Vpu hinge region residues towards enabling the protein to efficiently engage its target host proteins. Thus, this highly conserved, cytosolic Vpu hinge region may represent an attractive target for the

  13. The punctate localization of rat Eag1 K+ channels is conferred by the proximal post-CNBHD region.

    Science.gov (United States)

    Chuang, Chao-Chin; Jow, Guey-Mei; Lin, Huei-Min; Weng, Yu-Han; Hu, Jui-Hsiang; Peng, Yi-Jheng; Chiu, Yi-Chih; Chiu, Mei-Miao; Jeng, Chung-Jiuan

    2014-02-04

    In mammals, Eag K+ channels (KV10) are exclusively expressed in the brain and comprise two isoforms: Eag1 (KV10.1) and Eag2 (KV10.2). Despite their wide presence in various regions of the brain, the functional role of Eag K+ channels remains obscure. Here we address this question by characterizing the subcellular localization of rat Eag1 (rEag1) and rat Eag2 (rEag2) in hippocampal neurons, as well as determining the structural basis underlying their different localization patterns. Immunofluorescence analysis of young and mature hippocampal neurons in culture revealed that endogenous rEag1 and rEag2 K+ channels were present in both the dendrosomatic and the axonal compartments. Only rEag1 channels displayed a punctate immunostaining pattern and showed significant co-localization with PSD-95. Subcellular fractionation analysis further demonstrated a distinct enrichment of rEag1 in the synaptosomal fraction. Over-expression of recombinant GFP-tagged Eag constructs in hippocampal neurons also showed a significant punctate localization of rEag1 channels. To identify the protein region dictating the Eag channel subcellular localization pattern, we generated a variety of different chimeric constructs between rEag1 and rEag2. Quantitative studies of neurons over-expressing these GFP-tagged chimeras indicated that punctate localization was conferred by a segment (A723-R807) within the proximal post-cyclic nucleotide-binding homology domain (post-CNBHD) region in the rEag1 carboxyl terminus. Our findings suggest that Eag1 and Eag2 K+ channels may modulate membrane excitability in both the dendrosomatic and the axonal compartments and that Eag1 may additionally regulate neurotransmitter release and postsynaptic signaling. Furthermore, we present the first evidence showing that the proximal post-CNBHD region seems to govern the Eag K+ channel subcellular localization pattern.

  14. Intron DNA Sequences Can Be More Important Than the Proximal Promoter in Determining the Site of Transcript Initiation.

    Science.gov (United States)

    Gallegos, Jenna E; Rose, Alan B

    2017-04-01

    To more precisely define the positions from which certain intronic regulatory sequences increase mRNA accumulation, the effect of a UBIQUITIN intron on gene expression was tested from six different positions surrounding the transcription start site (TSS) of a reporter gene fusion in Arabidopsis thaliana The intron increased expression from all transcribed positions but had no effect when upstream of the 5'-most TSS. While this implies that the intron must be transcribed to increase expression, the TSS changed when the intron was located in the 5'-untranslated region (UTR), suggesting that the intron affects transcription initiation. Remarkably, deleting 303 nucleotides of the promoter including all known TSSs and all but 18 nucleotides of the 5'-UTR had virtually no effect on the level of gene expression as long as an intron containing stimulatory sequences was included. Instead, transcription was initiated in normally untranscribed sequences the same distance upstream of the intron as when the promoter was intact. These results suggest that certain intronic DNA sequences play unexpectedly large roles in directing transcription initiation and constitute a previously unrecognized type of downstream regulatory element for genes transcribed by RNA polymerase II. © 2017 American Society of Plant Biologists. All rights reserved.

  15. A 5'-proximal region of the Citrus tristeza virus genome encoding two leader proteases is involved in virus superinfection exclusion.

    Science.gov (United States)

    Atallah, Osama O; Kang, Sung-Hwan; El-Mohtar, Choaa A; Shilts, Turksen; Bergua, María; Folimonova, Svetlana Y

    2016-02-01

    Superinfection exclusion (SIE), a phenomenon in which a primary virus infection prevents a secondary infection with the same or closely related virus, has been observed with various viruses. Earlier we demonstrated that SIE by Citrus tristeza virus (CTV) requires viral p33 protein. In this work we show that p33 alone is not sufficient for virus exclusion. To define the additional viral components that are involved in this phenomenon, we engineered a hybrid virus in which a 5'-proximal region in the genome of the T36 isolate containing coding sequences for the two leader proteases L1 and L2 has been substituted with a corresponding region from the genome of a heterologous T68-1 isolate. Sequential inoculation of plants pre-infected with the CTV L1L2T68 hybrid with T36 CTV resulted in superinfection with the challenge virus, which indicated that the substitution of the L1-L2 coding region affected SIE ability of the virus. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Antibody humanization by redesign of complementarity-determining region residues proximate to the acceptor framework.

    Science.gov (United States)

    Hanf, Karl J M; Arndt, Joseph W; Chen, Ling Ling; Jarpe, Matthew; Boriack-Sjodin, P Ann; Li, You; van Vlijmen, Herman W T; Pepinsky, R Blake; Simon, Kenneth J; Lugovskoy, Alexey

    2014-01-01

    Antibodies are key components of the adaptive immune system and are well-established protein therapeutic agents. Typically high-affinity antibodies are obtained by immunization of rodent species that need to be humanized to reduce their immunogenicity. The complementarity-determining regions (CDRs) contain the residues in a defined loop structure that confer antigen binding, which must be retained in the humanized antibody. To design a humanized antibody, we graft the mature murine CDRs onto a germline human acceptor framework. Structural defects due to mismatches at the graft interface can be fixed by mutating some framework residues to murine, or by mutating some residues on the CDRs' backside to human or to a de novo designed sequence. The first approach, framework redesign, can yield an antibody with binding better than the CDR graft and one equivalent to the mature murine, and reduced immunogenicity. The second approach, CDR redesign, is presented here as a new approach, yielding an antibody with binding better than the CDR graft, and immunogenicity potentially less than that from framework redesign. Application of both approaches to the humanization of anti-α4 integrin antibody HP1/2 is presented and the concept of the hybrid humanization approach that retains "difficult to match" murine framework amino acids and uses de novo CDR design to minimize murine amino acid content and reduce cell-mediated cytotoxicity liabilities is discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Signals emanating from the membrane proximal region of the thrombopoietin receptor (mpl) support hematopoietic stem cell self-renewal.

    Science.gov (United States)

    Tong, Wei; Ibarra, Yessenia M; Lodish, Harvey F

    2007-09-01

    Studies using thrombopoietin -/- (TPO(-/-)) or TPO receptor, mpl(-/-) mice have established a critical role for TPO/mpl signaling in hematopoietic stem cell (HSC) development. In this study, we further dissected mpl signaling in both megakaryopoiesis and HSC function, using mice bearing a truncated mpl receptor lacking the distal 60 amino acids (Delta60). This deletion removes three major signaling tyrosines on the mpl cytoplasmic domain, but retains the membrane proximal Box1 and Box2 domains required for JAK2 activation. Competitive bone marrow transplantations (BMT) and serial BMTs were performed to study HSC function. Western blot analysis was used to study TPO-stimulated signaling pathways. BM cell cultures in the presence of TPO were used to study megakaryocyte development. In agreement with prior findings, we show that Delta60 BM cells cultured in TPO generated normal numbers of megakaryocytes, but with greatly reduced ploidy. As expected from the deletion of three signaling tyrosine residues, freshly isolated Delta60 megakaryocytes showed marked reduction in all known TPO-stimulated signaling pathways tested, including signal transducers and activators of transcription (Stat) 5, Stat3, Akt, and p42/44 mitogen-activated kinase. We found that Delta60 mice displayed normal short-term (ST-HSC) activities and marginally compromised long-term (LT-HSC) stem cell activities in primary transplantation. In addition, Delta60 mice supported HSC self-renewal for at least two serial BMTs. Our data reveal a pivotal role for an unknown signal emanating from the membrane proximal region of the mpl receptor or from JAK2 itself in maintaining stem cell activity and self-renewal, in addition to its role in megakaryocytopoiesis and thrombopoiesis.

  18. Engineering Recombinant Reoviruses To Display gp41 Membrane-Proximal External-Region Epitopes from HIV-1.

    Science.gov (United States)

    Boehme, Karl W; Ikizler, Mine'; Iskarpatyoti, Jason A; Wetzel, J Denise; Willis, Jordan; Crowe, James E; LaBranche, Celia C; Montefiori, David C; Wilson, Gregory J; Dermody, Terence S

    2016-01-01

    The gp41 membrane-proximal external region (MPER) is a target for broadly neutralizing antibody responses against human immunodeficiency virus type 1 (HIV-1). However, replication-defective virus vaccines currently under evaluation in clinical trials do not efficiently elicit MPER-specific antibodies. Structural modeling suggests that the MPER forms an α-helical coiled coil that is required for function and immunogenicity. To maintain the native MPER conformation, we used reverse genetics to engineer replication-competent reovirus vectors that displayed MPER sequences in the α-helical coiled-coil tail domain of viral attachment protein σ1. Sequences in reovirus strain type 1 Lang (T1L) σ1 were exchanged with sequences encoding HIV-1 strain Ba-L MPER epitope 2F5 or the entire MPER. Individual 2F5 or MPER substitutions were introduced at virion-proximal or virion-distal sites in the σ1 tail. Recombinant reoviruses containing heterologous HIV-1 sequences were viable and produced progeny yields comparable to those with wild-type virus. HIV-1 sequences were retained following 10 serial passages in cell culture, indicating that the substitutions were genetically stable. Recombinant viruses engineered to display the 2F5 epitope or full-length MPER in σ1 were recognized by purified 2F5 antibody. Inoculation of mice with 2F5-containing vectors or rabbits with 2F5- or MPER-containing vectors elicited anti-reovirus antibodies, but HIV-1-specific antibodies were not detected. Together, these findings indicate that heterologous sequences that form α-helices can functionally replace native sequences in the α-helical tail domain of reovirus attachment protein σ1. However, although these vectors retain native antigenicity, they were not immunogenic, illustrating the difficulty of experimentally inducing immune responses to this essential region of HIV-1. IMPORTANCE Vaccines to protect against HIV-1, the causative agent of AIDS, are not approved for use. Antibodies that

  19. Promotion and regional development. Implementation of regional productive development agencies. The case of Maule region, Chile

    Directory of Open Access Journals (Sweden)

    Enrique Yamil Alul González

    2010-12-01

    Full Text Available The Regional Productive Development Agencies implemented in Chile in 2006, were developed as a way to answer the longing desire to territorially decentralize, and that the own Regions be whom define their future. The Agencies have the responsibility to develop innovation and productive development Agendas in participative processes, which means with public, academic and private actors. Also, the Agencies have the mission to implement Competitive Improvement Plans-PMC (clusters in prioritized economic sectors by the own region. These PMC are leaded by private actors in each sector.

  20. Distal, not proximal, colonic acetate infusions promote fat oxidation and improve metabolic markers in overweight/obese men

    DEFF Research Database (Denmark)

    van der Beek, Christina M; Canfora, Emanuel E; Lenaerts, Kaatje

    2016-01-01

    in the colon for three consecutive test days, enabling colonic acetate (100 or 180 mmol/l) or placebo infusion during fasting conditions and after an oral glucose load (postprandial). Fat oxidation and energy expenditure were measured using an open-circuit ventilated hood system and blood samples were......Gut microbial-derived short-chain fatty acids (SCFA) are believed to affect host metabolism and cardiometabolic risk factors. The present study aim was to investigate the effects of proximal and distal colonic infusions with the SCFA acetate on fat oxidation and other metabolic parameters in men....... In this randomized, double-blind crossover trial, six overweight/obese men [body mass index (BMI) 25-35 kg/m(2)] underwent two experimental periods: one with distal and one with proximal colonic sodium acetate infusions. A feeding catheter was endoscopically positioned at the beginning of each period and remained...

  1. Modulating immunogenic properties of HIV-1 gp41 membrane-proximal external region by destabilizing six-helix bundle structure

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, Saikat; Shi, Heliang; Habte, Habtom H.; Qin, Yali; Cho, Michael W., E-mail: mcho@iastate.edu

    2016-03-15

    The C-terminal alpha-helix of gp41 membrane-proximal external region (MPER; {sup 671}NWFDITNWLWYIK{sup 683}) encompassing 4E10/10E8 epitopes is an attractive target for HIV-1 vaccine development. We previously reported that gp41-HR1-54Q, a trimeric protein comprised of the MPER in the context of a stable six-helix bundle (6HB), induced strong immune responses against the helix, but antibodies were directed primarily against the non-neutralizing face of the helix. To better target 4E10/10E8 epitopes, we generated four putative fusion intermediates by introducing double point mutations or deletions in the heptad repeat region 1 (HR1) that destabilize 6HB in varying degrees. One variant, HR1-∆10-54K, elicited antibodies in rabbits that targeted W672, I675 and L679, which are critical for 4E10/10E8 recognition. Overall, the results demonstrated that altering structural parameters of 6HB can influence immunogenic properties of the MPER and antibody targeting. Further exploration of this strategy could allow development of immunogens that could lead to induction of 4E10/10E8-like antibodies. - Highlights: • Four gp41 MPER-based immunogens that resemble fusion intermediates were generated. • C-terminal region of MPER that contains 4E10/10E8 epitopes was highly immunogenic. • Altering 6HB structure can influence immunogenic properties of the MPER. • Induced antibodies targeted multiple residues critical for 4E10/10E8 binding. • Development of immunogens based on fusion intermediates is a promising strategy.

  2. Exploring the determinants of health and wellbeing in communities living in proximity to coal seam gas developments in regional Queensland

    Directory of Open Access Journals (Sweden)

    Fiona Mactaggart

    2017-08-01

    Full Text Available Abstract Background There is some concern that coal seam gas mining may affect health and wellbeing through changes in social determinants such as living and working conditions, local economy and the environment. The onward impact of these conditions on health and wellbeing is often not monitored to the same degree as direct environmental health impacts in the mining context, but merits attention. This study reports on the findings from a recurrent theme that emerged from analysis of the qualitative component of a comprehensive Health Needs Assessment (HNA conducted in regional Queensland: that health and wellbeing of communities was reportedly affected by nearby coal seam gas (CSG development beyond direct environmental impacts. Methods Qualitative analysis was initially completed using the Framework Method to explore key themes from 11 focus group discussions, 19 in-depth interviews, and 45 key informant interviews with health and wellbeing service providers and community members. A key theme emerged from the analysis that forms the basis of this paper. This study is part of a larger comprehensive HNA involving qualitative and quantitative data collection to explore the health and wellbeing needs of three communities living in proximity to CSG development in regional Queensland, Australia. Results Communities faced social, economic and environmental impacts from the rapid growth of CSG development, which were perceived to have direct and indirect effects on individual lifestyle factors such as alcohol and drug abuse, family relationships, social capital and mental health; and community-level factors including social connectedness, civic engagement and trust. Conclusions Outer regional communities discussed the effects of mining activity on the fabric of their town and community, whereas the inner regional community that had a longer history of industrial activity discussed the impacts on families and individual health and wellbeing. The

  3. Identification of chromatin marks at TERRA promoter and encoding region.

    Science.gov (United States)

    Negishi, Yutaka; Kawaji, Hideya; Minoda, Aki; Usui, Kengo

    2015-11-27

    TERRA is a long non-coding RNA that is essential for telomere integrity. Although it is transcribed from subtelomeres and telomeres, how it is expressed in heterochromatic region is currently unknown. In this study, we focused our analysis on TERRA-encoding region TelBam3.4 and TelBam3.4-like sequences, and determined their transcription start sites, as well as enrichment of RNA polymerase II and histone modifications. We found that H3K4me3 and H3K9me3 are present at TERRA promoters, whereas H3K27ac and H3K9me3 are present at telomeric repeats. Consistently, we show that presence of active histone modifications H3K4me3 and H3K27ac are correlated to TERRA expression. These results mark an important step towards understanding telomere maintenance and transcription. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Beyond regional clusters: On the importance of geographical proximity for R&D collaborations in a global economy - the case of the flemisch biotech sector

    NARCIS (Netherlands)

    Herrmann, A.M.; Taks, J.L.; Moors, E.H.M.

    2012-01-01

    When internal knowledge bases are insufficient for developing innovations, companies tend to collaborate with external R&D partners. According to a long-standing literature on “clusters”, “industrial districts”, “local production systems” and “regional innovation systems”, geographical proximity

  5. Uric acid promotes apoptosis in human proximal tubule cells by oxidative stress and the activation of NADPH oxidase NOX 4.

    Directory of Open Access Journals (Sweden)

    Daniela Verzola

    Full Text Available Mild hyperuricemia has been linked to the development and progression of tubulointerstitial renal damage. However the mechanisms by which uric acid may cause these effects are poorly explored. We investigated the effect of uric acid on apoptosis and the underlying mechanisms in a human proximal tubule cell line (HK-2. Increased uric acid concentration decreased tubule cell viability and increased apoptotic cells in a dose dependent manner (up to a 7-fold increase, p<0.0001. Uric acid up-regulated Bax (+60% with respect to Ctrl; p<0.05 and down regulated X-linked inhibitor of apoptosis protein. Apoptosis was blunted by Caspase-9 but not Caspase-8 inhibition. Uric acid induced changes in the mitochondrial membrane, elevations in reactive oxygen species and a pronounced up-regulation of NOX 4 mRNA and protein (p<0.05. In addition, both reactive oxygen species production and apoptosis was prevented by the NADPH oxidase inhibitor DPI as well as by Nox 4 knockdown. URAT 1 transport inhibition by probenecid and losartan and its knock down by specific siRNA, blunted apoptosis, suggesting a URAT 1 dependent cell death. In summary, our data show that uric acid increases the permissiveness of proximal tubule kidney cells to apoptosis by triggering a pathway involving NADPH oxidase signalling and URAT 1 transport. These results might explain the chronic tubulointerstitial damage observed in hyperuricaemic states and suggest that uric acid transport in tubular cells is necessary for urate-induced effects.

  6. Tropical Texture Determination by Proximal Sensing Using a Regional Spectral Library and Its Relationship with Soil Classification

    Directory of Open Access Journals (Sweden)

    Marilusa P. C. Lacerda

    2016-08-01

    Full Text Available The search for sustainable land use has increased in Brazil due to the important role that agriculture plays in the country. Soil detailed classification is related with texture attribute. How can one discriminate the same soil class with different textures using proximal soil sensing, as to reach surveys, land use planning and increase crop productivity? This study aims to evaluate soil texture using a regional spectral library and its usefulness on classification. We collected 3750 soil samples covering 3 million ha within strong soil class variations in São Paulo State. The spectral analyses of soil samples from topsoil and subsoil were measured in laboratory (400–2500 nm. The potential of a regional soil spectral library was evaluated on the discrimination of soil texture. We considered two types of soil texture systems, one related with soil classification and another with soil managements. The soil line technique was used to assess differentiation between soil textural groups. Soil spectra were summarized by principal component analysis (PCA to select relevant information on the spectra. Partial least squares regression (PLSR was used to predict texture. Spectral curves indicated different shapes according to soil texture and discriminated particle size classes from clayey to sandy soils. In the visible region, differences were small because of the organic matter, while the short wave infrared (SWIR region showed more differences; thus, soil texture variation could be differentiated by quartz. Angulation differences are on a spectral curve from NIR to SWIR. The statistical models predicted clay and sand levels with R2 = 0.93 and 0.96, respectively. Indeed, we achieved a difference of 1.2% between laboratory and spectroscopy measurement for clay. The spectral information was useful to classify Ferralsols with different texture classification. In addition, the spectra differentiated Lixisols from Ferralsols and Arenosols. This work can

  7. Targeting antibody responses to the membrane proximal external region of the envelope glycoprotein of human immunodeficiency virus.

    Directory of Open Access Journals (Sweden)

    Donatien Kamdem Toukam

    Full Text Available Although human immunodeficiency type 1 (HIV-1 infection induces strong antibody responses to the viral envelope glycoprotein (Env only a few of these antibodies possess the capacity to neutralize a broad range of strains. The induction of such antibodies represents an important goal in the development of a preventive vaccine against the infection. Among the broadly neutralizing monoclonal antibodies discovered so far, three (2F5, Z13 and 4E10 target the short and hidden membrane proximal external region (MPER of the gp41 transmembrane protein. Antibody responses to MPER are rarely observed in HIV-infected individuals or after immunization with Env immunogens. To initiate antibody responses to MPER in its membrane-embedded native conformation, we generated expression plasmids encoding the membrane-anchored ectodomain of gp41 with N-terminal deletions of various sizes. Following transfection of these plasmids, the MPER domains are displayed on the cell surface and incorporated into HIV virus like particles (VLP. Transfected cells displaying MPER mutants bound as efficiently to both 2F5 and 4E10 as cells transfected with a plasmid encoding full-length Env. Mice immunized with VLPs containing the MPER mutants produced MPER-specific antibodies, the levels of which could be increased by the trimerization of the displayed proteins as well as by a DNA prime-VLP boost immunization strategy. Although 2F5 competed for binding to MPER with antibodies in sera of some of the immunized mice, neutralizing activity could not be detected. Whether this is due to inefficient binding of the induced antibodies to MPER in the context of wild type Env or whether the overall MPER-specific antibody response induced by the MPER display mutants is too low to reveal neutralizing activity, remains to be determined.

  8. The effect of mutations in the AmpC promoter region on β-lactam ...

    African Journals Online (AJOL)

    Analysis of the ampC promoter and attenuator regions of the isolate showed that the isolate had mutations in the promoter region and this included insertions of nucleotides in ... The insertion of an extra nucleotide in the spacer region between the -10 and -35 boxes affects the resistance of bacteria to β-lactam antibiotics.

  9. Distal promoter regions are responsible for differential regulation of human orosomucoid-1 and -2 gene expression and acute phase responses.

    Science.gov (United States)

    Sai, Kimie; Kurose, Kouichi; Koizumi, Tomoko; Katori, Noriko; Sawada, Jun-ichi; Matsumura, Yasuhiro; Saijo, Nagahiro; Yamamoto, Noboru; Tamura, Tomohide; Okuda, Haruhiro; Saito, Yoshiro

    2014-01-01

    Human orosomucoid (ORM) is a major acute-phase plasma protein, encoded by 2 highly homologous genes, ORM1 and ORM2. Human ORM induction is assumed to be regulated by each proximal promoter region, where putative glucocorticoid responsive elements and CCAAT/enhancer binding protein (C/EBP)β binding sites are located. However, the details of the differential regulation of these genes remain unknown. To explore this, we assessed the role of the distal promoter region of each ORM in HeLa cells. Luciferase-reporter activities of full constructs, containing approximately 1.1 kbp (FULL), and those of deletion constructs, containing up to 188 bp region (DEL) upstream of the transcription start sites of ORM1 and ORM2 were compared under both basal and inducer-treated conditions. For ORM1 and ORM2 DEL constructs, significantly increased activities after dexamethasone (DEX) treatments (alone and combined with interleukin (IL)-1β) were observed. Significantly higher FULL construct activities than DEL construct activities were observed for ORM1 after IL-1β treatment, while those for ORM2 were significantly lower at basal level and after DEX treatments. Upon C/EBPβ overexpression, FULL construct activities were significantly higher than those of DEL constructs at basal level and after IL-1β treatment for ORM1, and at basal level and after inducer-treatments for ORM2. Higher transcription-induction activity in the distal promoter region was evident for ORM1 in the absence of C/EBPβ overexpression, and for ORM2 under C/EBPβ overexpression conditions. These findings suggest that the ORM distal promoter region differentially regulates expression of ORM genes at basal level and in acute phase responses.

  10. RET Recognition of GDNF-GFRα1 Ligand by a Composite Binding Site Promotes Membrane-Proximal Self-Association

    Directory of Open Access Journals (Sweden)

    Kerry M. Goodman

    2014-09-01

    Full Text Available The RET receptor tyrosine kinase is essential to vertebrate development and implicated in multiple human diseases. RET binds a cell surface bipartite ligand comprising a GDNF family ligand and a GFRα coreceptor, resulting in RET transmembrane signaling. We present a hybrid structural model, derived from electron microscopy (EM and low-angle X-ray scattering (SAXS data, of the RET extracellular domain (RETECD, GDNF, and GFRα1 ternary complex, defining the basis for ligand recognition. RETECD envelopes the dimeric ligand complex through a composite binding site comprising four discrete contact sites. The GFRα1-mediated contacts are crucial, particularly close to the invariant RET calcium-binding site, whereas few direct contacts are made by GDNF, explaining how distinct ligand/coreceptor pairs are accommodated. The RETECD cysteine-rich domain (CRD contacts both ligand components and makes homotypic membrane-proximal interactions occluding three different antibody epitopes. Coupling of these CRD-mediated interactions suggests models for ligand-induced RET activation and ligand-independent oncogenic deregulation.

  11. Cloning and characterization of the promoter regions from the parent and paralogous creatine transporter genes.

    Science.gov (United States)

    Ndika, Joseph D T; Lusink, Vera; Beaubrun, Claudine; Kanhai, Warsha; Martinez-Munoz, Cristina; Jakobs, Cornelis; Salomons, Gajja S

    2014-01-10

    Interconversion between phosphocreatine and creatine, catalyzed by creatine kinase is crucial in the supply of ATP to tissues with high energy demand. Creatine's importance has been established by its use as an ergogenic aid in sport, as well as the development of intellectual disability in patients with congenital creatine deficiency. Creatine biosynthesis is complemented by dietary creatine uptake. Intracellular transport of creatine is carried out by a creatine transporter protein (CT1/CRT/CRTR) encoded by the SLC6A8 gene. Most tissues express this gene, with highest levels detected in skeletal muscle and kidney. There are lower levels of the gene detected in colon, brain, heart, testis and prostate. The mechanism(s) by which this regulation occurs is still poorly understood. A duplicated unprocessed pseudogene of SLC6A8-SLC6A10P has been mapped to chromosome 16p11.2 (contains the entire SLC6A8 gene, plus 2293 bp of 5'flanking sequence and its entire 3'UTR). Expression of SLC6A10P has so far only been shown in human testis and brain. It is still unclear as to what is the function of SLC6A10P. In a patient with autism, a chromosomal breakpoint that intersects the 5'flanking region of SLC6A10P was identified; suggesting that SLC6A10P is a non-coding RNA involved in autism. Our aim was to investigate the presence of cis-acting factor(s) that regulate expression of the creatine transporter, as well as to determine if these factors are functionally conserved upstream of the creatine transporter pseudogene. Via gene-specific PCR, cloning and functional luciferase assays we identified a 1104 bp sequence proximal to the mRNA start site of the SLC6A8 gene with promoter activity in five cell types. The corresponding 5'flanking sequence (1050 bp) on the pseudogene also had promoter activity in all 5 cell lines. Surprisingly the pseudogene promoter was stronger than that of its parent gene in 4 of the cell lines tested. To the best of our knowledge, this is the first

  12. Zinc ions upregulate the hormone gastrin via an E-box motif in the proximal gastrin promoter.

    Science.gov (United States)

    Xiao, Lin; Kovac, Suzana; Chang, Mike; Shulkes, Arthur; Baldwin, Graham S; Patel, Oneel

    2014-02-01

    Gastrin and its precursors act as growth factors for the normal and neoplastic gastrointestinal mucosa. As the hypoxia mimetic cobalt chloride upregulates the gastrin gene, the effect of other metal ions on gastrin promoter activity was investigated. Gastrin mRNA was measured by real-time PCR, gastrin peptides by RIA, and gastrin promoter activity by dual-luciferase reporter assay. Exposure to Zn(2)(+) ions increased gastrin mRNA concentrations in the human gastric adenocarcinoma cell line AGS in a dose-dependent manner, with a maximum stimulation of 55 ± 14-fold at 100 μM (Pgastrin induction by Zn(2)(+). Deletional mutation of the gastrin promoter identified an 11 bp DNA sequence, which contained an E-box motif, as necessary for Zn(2)(+)-dependent gastrin induction. The fact that E-box binding transcription factors play a crucial role in the epithelial-mesenchymal transition (EMT), together with our observation that Zn(2)(+) ions upregulate the gastrin gene in AGS cells by an E-box-dependent mechanism, suggests that Zn(2)(+) ions may induce an EMT, and that gastrin may be involved in the transition.

  13. High-quality annotation of promoter regions for 913 bacterial genomes.

    Science.gov (United States)

    Rangannan, Vetriselvi; Bansal, Manju

    2010-12-15

    The number of bacterial genomes being sequenced is increasing very rapidly and hence, it is crucial to have procedures for rapid and reliable annotation of their functional elements such as promoter regions, which control the expression of each gene or each transcription unit of the genome. The present work addresses this requirement and presents a generic method applicable across organisms. Relative stability of the DNA double helical sequences has been used to discriminate promoter regions from non-promoter regions. Based on the difference in stability between neighboring regions, an algorithm has been implemented to predict promoter regions on a large scale over 913 microbial genome sequences. The average free energy values for the promoter regions as well as their downstream regions are found to differ, depending on their GC content. Threshold values to identify promoter regions have been derived using sequences flanking a subset of translation start sites from all microbial genomes and then used to predict promoters over the complete genome sequences. An average recall value of 72% (which indicates the percentage of protein and RNA coding genes with predicted promoter regions assigned to them) and precision of 56% is achieved over the 913 microbial genome dataset. The binary executable for 'PromPredict' algorithm (implemented in PERL and supported on Linux and MS Windows) and the predicted promoter data for all 913 microbial genomes are available at http://nucleix.mbu.iisc.ernet.in/prombase/.

  14. Nef decreases HIV-1 sensitivity to neutralizing antibodies that target the membrane-proximal external region of TMgp41.

    Directory of Open Access Journals (Sweden)

    Rachel P J Lai

    2011-12-01

    Full Text Available Primate lentivirus nef is required for sustained virus replication in vivo and accelerated progression to AIDS. While exploring the mechanism by which Nef increases the infectivity of cell-free virions, we investigated a functional link between Nef and Env. Since we failed to detect an effect of Nef on the quantity of virion-associated Env, we searched for qualitative changes by examining whether Nef alters HIV-1 sensitivity to agents that target distinct features of Env. Nef conferred as much as 50-fold resistance to 2F5 and 4E10, two potent neutralizing monoclonal antibodies (nAbs that target the membrane proximal external region (MPER of TMgp41. In contrast, Nef had no effect on HIV-1 neutralization by MPER-specific nAb Z13e1, by the peptide inhibitor T20, nor by a panel of nAbs and other reagents targeting gp120. Resistance to neutralization by 2F5 and 4E10 was observed with Nef from a diverse range of HIV-1 and SIV isolates, as well as with HIV-1 virions bearing Env from CCR5- and CXCR4-tropic viruses, clade B and C viruses, or primary isolates. Functional analysis of a panel of Nef mutants revealed that this activity requires Nef myristoylation but that it is genetically separable from other Nef functions such as the ability to enhance virus infectivity and to downregulate CD4. Glycosylated-Gag from MoMLV substituted for Nef in conferring resistance to 2F5 and 4E10, indicating that this activity is conserved in a retrovirus that does not encode Nef. Given the reported membrane-dependence of MPER-recognition by 2F5 and 4E10, in contrast to the membrane-independence of Z13e1, the data here is consistent with a model in which Nef alters MPER recognition in the context of the virion membrane. Indeed, Nef and Glycosylated-Gag decreased the efficiency of virion capture by 2F5 and 4E10, but not by other nAbs. These studies demonstrate that Nef protects lentiviruses from one of the most broadly-acting classes of neutralizing antibodies. This newly

  15. Human ciliary neurotrophic factor: Localization to the proximal region of the long arm of chromosome 11 and association with CA/GT dinucleotide repeat

    Energy Technology Data Exchange (ETDEWEB)

    Lev, A.A.; Rosen, D.R.; Kos, C.; Brown, R.H. Jr.; Clifford, E.; Landes, G.; Hauser, S.L.

    1993-05-01

    Ciliary neurotrophic factor (CNTF) promotes survival and differentiation of several types of sensory, motor, sympathetic, and parasympathetic neurons. The authors have used the polymerase chain reaction to amplify, clone, and partially sequence CNTF cDNA from human muscle. Using a rodent-human mapping panel and fluorescence in situ hybridization, they have localized a single copy of the gene for human CNTF to the proximal long arm of chromosome 11. They have also identified a polymorphic tandem CA/GT dinucleotide repeat associated with the human CNTF gene. 14 refs., 1 fig.

  16. Evidence for TGF-beta1 and bleomycin intracellular signaling through autocrine regulation of Smad 3 binding to the proximal promoter of the Smad 7 gene.

    Science.gov (United States)

    Cutroneo, Kenneth R

    2006-04-01

    Both Bleomycin and TGF-beta1 increase the transcription of the COL1A1 gene. Bleomycin acts through TGF-beta1. Bleomycin stimulates the COL1A1 promoter through the distal TGF-beta response element by intracellular and extracellular signaling. As demonstrated in this manuscript, Bleomycin's intracellular signaling can be explained by a decrease of Smad 3 transcription factor binding to the SBE located in the proximal promoter of the inhibitory Smad 7 gene. This would result in TGF-beta1-induced activated SMADS, which would result in more collagen. Bleomycin's extracellular signaling results from the secretion of more latent TGF-beta produced by lung fibroblasts and cleaved to active TGF-beta extracellularly. Since the TGF-beta genes are auto-induced in human embryonic IMR-90 lung fibroblasts, this study indicates an autocrine mechanism to maintain homeostasis in vivo for fibroblasts and other cell types, which produce TGF-beta1 to limit the fibrogenic response to TGF-beta1 and Bleomycin. (c) 2005 Wiley-Liss, Inc.

  17. DNA methylation of PTEN gene promoter region is not correlated ...

    African Journals Online (AJOL)

    Yomi

    2012-02-23

    Feb 23, 2012 ... Tumor suppressor gene PTEN plays an important role in cell cycle. Disorder of PTEN protein can cause cell growth and division in an uncontrolled way, which can lead to the formation of tumors. It has been proven that epigenetic mechanisms, such as promoter hypermethylation, may account for ...

  18. DNA methylation of PTEN gene promoter region is not correlated ...

    African Journals Online (AJOL)

    Tumor suppressor gene PTEN plays an important role in cell cycle. Disorder of PTEN protein can cause cell growth and division in an uncontrolled way, which can lead to the formation of tumors. It has been proven that epigenetic mechanisms, such as promoter hypermethylation, may account for inactivation of PTEN in a ...

  19. Proximal Hypospadias

    Science.gov (United States)

    Kraft, Kate H.; Shukla, Aseem R.; Canning, Douglas A.

    2011-01-01

    Hypospadias results from abnormal development of the penis that leaves the urethral meatus proximal to its normal glanular position. Meatal position may be located anywhere along the penile shaft, but more severe forms of hypospadias may have a urethral meatus located at the scrotum or perineum. The spectrum of abnormalities may also include ventral curvature of the penis, a dorsally redundant prepuce, and atrophic corpus spongiosum. Due to the severity of these abnormalities, proximal hypospadias often requires more extensive reconstruction in order to achieve an anatomically and functionally successful result. We review the spectrum of proximal hypospadias etiology, presentation, correction, and possible associated complications. PMID:21516286

  20. The Digital North Denmark Programme -Promoting Regional Change?

    DEFF Research Database (Denmark)

    Østergaard, Christian Richter

    2007-01-01

    (Dybkjær and Lindegaard, 1999, p.96-100). The declared approach was to build on the existing competencies in industry as well as at universities. The national government chose two regions – Ørestaden, a new concentration of knowledge-based institutions near Copenhagen Airport, and North Jutland...... of development perspectives for the regional ICT sector will focus on the participation of the university and the cluster....

  1. A distal region of the human TGM1 promoter is required for expression in transgenic mice and cultured keratinocytes

    Directory of Open Access Journals (Sweden)

    Lu Ying

    2004-04-01

    Full Text Available Abstract Background TGM1(transglutaminase 1 is an enzyme that crosslinks the cornified envelope of mature keratinocytes. Appropriate expression of the TGM1 gene is crucial for proper keratinocyte function as inactivating mutations lead to the debilitating skin disease, lamellar ichthyosis. TGM1 is also expressed in squamous metaplasia, a consequence in some epithelia of vitamin A deficiency or toxic insult that can lead to neoplasia. An understanding of the regulation of this gene in normal and abnormal differentiation states may contribute to better disease diagnosis and treatment. Methods In vivo requirements for expression of the TGM1 gene were studied by fusing various lengths of promoter DNA to a reporter and injecting the DNA into mouse embryos to generate transgenic animals. Expression of the reporter was ascertained by Western blotting and immunohistochemistry. Further delineation of a transcriptionally important distal region was determined by transfections of progressively shortened or mutated promoter DNA into cultured keratinocytes. Results In vivo analysis of a reporter transgene driven by the TGM1 promoter revealed that 1.6 kilobases, but not 1.1 kilobases, of DNA was sufficient to confer tissue-specific and cell layer-specific expression. This same region was responsible for reporter expression in tissues undergoing squamous metaplasia as a response to vitamin A deprivation. Mutation of a distal promoter AP1 site or proximal promoter CRE site, both identified as important transcriptional elements in transfection assays, did not prevent appropriate expression. Further searching for transcriptional elements using electrophoretic mobility shift (EMSA and transfection assays in cultured keratinocytes identified two Sp1 elements in a transcriptionally active region between -1.6 and -1.4 kilobases. While mutation of either Sp1 site or the AP1 site singly had only a small effect, mutation of all three sites eliminated nearly all the

  2. Transcriptional Activity of the FUT1 Gene Promoter Region in Pigs

    Directory of Open Access Journals (Sweden)

    Chen Zi

    2013-12-01

    Full Text Available This study aims to provide a theoretical basis on the regulatory mechanism of the α-l,2-fucosyltransferase (FUT1 gene in pigs by analyzing the transcriptional activity of its promoter region. On the basis of the previously obtained promoter sequence, primers upstream and downstream of the gene were designed using the restriction endonucleases KpnI and HindIII respectively, and the recombinant plasmids of the pGL3-promoter were constructed by inserting promoter sequences with partially missing regions. The resultant mutants were observed by transient transfection assay into HEK293 cells, and the transcriptional activity of the promoter region was determined by luciferase activity. The 5'-flanking region of the FUT1 gene (−1150 to +50 bp exhibited promoter activity. The −1150-bp to −849-bp region showed negative regulation of the gene. The recombinant plasmid pGL3-898 showed the strongest luciferase activity, and the activity showed a decreasing trend when the deleted region was increased. Recombinant plasmids were successfully constructed, verified, and the positive and negative regulation areas and core promoter region were detected, providing a deeper insight into the transcriptional regulatory mechanism of the FUT1 gene.

  3. Humoral Immunogenicity of an HIV-1 Envelope Residue 649-684 Membrane-proximal Region Peptide Fused to the Plague Antigen F1-V

    OpenAIRE

    Matoba, Nobuyuki; Shah, Namrata Rahul; Tsafrir S. Mor

    2011-01-01

    The membrane-proximal region spanning residues 649-684 of the HIV-1 envelope protein gp41 (MPR649-684) is an attractive vaccine target for humoral immunity that blocks viral transcytosis across the mucosal epithelia. However, induction of high-titer MPR649-684-specific antibodies remains a challenging task. To explore potential solutions for this challenge, we tested a new translational fusion protein comprising the plague F1-V antigen and MPR649-684 (F1-V-MPR649-684). We employed systemic im...

  4. Promoter regions of Plasmodium vivax are poorly or not recognized by Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    del Portillo Hernando A

    2007-02-01

    Full Text Available Abstract Background Heterologous promoter analysis in Plasmodium has revealed the existence of conserved cis regulatory elements as promoters from different species can drive expression of reporter genes in heterologous transfection assays. Here, the functional characterization of different Plasmodium vivax promoters in Plasmodium falciparum using luciferase as the reporter gene is presented. Methods Luciferase reporter plasmids harboring the upstream regions of the msp1, dhfr, and vir3 genes as well as the full-length intergenic regions of the vir23/24 and ef-1α genes of P. vivax were constructed and transiently transfected in P. falciparum. Results Only the constructs with the full-length intergenic regions of the vir23/24 and ef-1α genes were recognized by the P. falciparum transcription machinery albeit to values approximately two orders of magnitude lower than those reported by luc plasmids harbouring promoter regions from P. falciparum and Plasmodium berghei. A bioinformatics approach allowed the identification of a motif (GCATAT in the ef-1α intergenic region that is conserved in five Plasmodium species but is degenerate (GCANAN in P. vivax. Mutations of this motif in the P. berghei ef-1α promoter region decreased reporter expression indicating it is active in gene expression in Plasmodium. Conclusion Together, this data indicates that promoter regions of P. vivax are poorly or not recognized by the P. falciparum transcription machinery suggesting the existence of P. vivax-specific transcription regulatory elements.

  5. Genotoxic effects and serum abnormalities in residents of regions proximal to e-waste disposal facilities in Jinghai, China.

    Science.gov (United States)

    Li, KeQiu; Liu, ShaSha; Yang, QiaoYun; Zhao, YuXia; Zuo, JunFang; Li, Ran; Jing, YaQing; He, XiaoBo; Qiu, XingHua; Li, Guang; Zhu, Tong

    2014-07-01

    Electronic waste (e-waste) disposal is a growing problem in China, and its effects on human health are a concern. To determine the concentrations of pollutants in peripheral blood and genetic aberrations near an e-waste disposal area in Jinghai, China, blood samples were collected from 30 (age: 41±11.01 years) and 28 (age: 33±2.14 years) individuals residing within 5 and 40km of e-waste disposal facilities in Jinghai (China), respectively, during the week of October 21-28, 2011. Levels of inorganic pollutants (calcium, copper, iron, lead, magnesium, selenium, and zinc) and malondialdehyde (MDA), identities of persistent organic pollutants (POPs), micronucleus rates, and lymphocyte subsets were analyzed in individuals. Total RNA expression profiles were analyzed by group and gender. The population group living in proximity to the e-waste site displayed significantly higher mean levels of copper, zinc, lead, MDAs, POPs (B4-6DE, B7-9DE, total polychlorinated biphenyls, and BB-153). In addition, micronucleus rates of close-proximity group were higher compared with the remote group (18.27% vs. 7.32%). RNA expression of genes involved in metal ion binding and transport, oxidation/reduction, immune defense, and tumorigenesis varied between groups, with men most detrimentally affected (pe-waste group (pe-waste disposal facilities (≤5km) may be associated with the accumulation of potentially harmful inorganic/organic compounds and gender-preferential genetic aberrations. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Social Media Marketing as a tool for promoting the regional investment portals

    Directory of Open Access Journals (Sweden)

    Alisa Yu. Fadeyeva

    2016-01-01

    Full Text Available Objective to investigate the potential of Social Media Marketing as a tool for promoting regional investment portals in the information environment to identify the most effective ways of its implementation and to determine the level of mastering of this tool by the Russian regions. Methods general scientific methods observation comparison analysis induction deduction analogy classification. Results the analysis showed that today Social Media Marketing is an essential tool for interaction with the investment community and one of the most effective ways to promote the regional portal which allows to increase the knowledge of and loyalty to the brand to increase the targeted website traffic to increase the awareness of investors about the specific features of the portal and the regional development agenciesrsquo functioning to promptly receive information about the investment environment and to establish contacts with investors. At the same time the study of SMMactivity in the Russian regions revealed a very low level of quality of communication with investors through social networks. Scientific novelty for the first time the article investigates the significance and makes the comparative analysis of the Social Media Marketing channels with regard to investment promotion agencies as well as the results of the regional structures functioning for effective communication through social networks. Practical significance the main results of the research can be used by the regional investment agencies in order to promote their websites increase the quality of communication with investors and promote the investment attractiveness of the region as a whole. nbsp

  7. Genome-wide analysis of regions similar to promoters of histone genes

    KAUST Repository

    Chowdhary, Rajesh

    2010-05-28

    Background: The purpose of this study is to: i) develop a computational model of promoters of human histone-encoding genes (shortly histone genes), an important class of genes that participate in various critical cellular processes, ii) use the model so developed to identify regions across the human genome that have similar structure as promoters of histone genes; such regions could represent potential genomic regulatory regions, e.g. promoters, of genes that may be coregulated with histone genes, and iii/ identify in this way genes that have high likelihood of being coregulated with the histone genes.Results: We successfully developed a histone promoter model using a comprehensive collection of histone genes. Based on leave-one-out cross-validation test, the model produced good prediction accuracy (94.1% sensitivity, 92.6% specificity, and 92.8% positive predictive value). We used this model to predict across the genome a number of genes that shared similar promoter structures with the histone gene promoters. We thus hypothesize that these predicted genes could be coregulated with histone genes. This hypothesis matches well with the available gene expression, gene ontology, and pathways data. Jointly with promoters of the above-mentioned genes, we found a large number of intergenic regions with similar structure as histone promoters.Conclusions: This study represents one of the most comprehensive computational analyses conducted thus far on a genome-wide scale of promoters of human histone genes. Our analysis suggests a number of other human genes that share a high similarity of promoter structure with the histone genes and thus are highly likely to be coregulated, and consequently coexpressed, with the histone genes. We also found that there are a large number of intergenic regions across the genome with their structures similar to promoters of histone genes. These regions may be promoters of yet unidentified genes, or may represent remote control regions that

  8. How to promote the regional cooperation in Asia

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, Masayuki [International Affairs and Safeguards Division, Atomic Energy Bureau, Science and Technology Agency, Tokyo (Japan)

    2000-12-01

    The Tenth International Conference for Nuclear Cooperation in Asia was held in Tokyo on March 10, 1999. Representatives participated from Australia, China, Indonesia, Japan, Korea, Malaysia, the Philippines, Thailand, and Vietnam as well as IAEA as an observer. The countries reflected on the positive achievements of the past ten years and affirmed the major goals for the future, the major theme of the meeting being the evolution of the framework. Some typical cooperative activities have result in: (a) new varieties of plants with greater productivity under a range of environmental conditions (b) development and adoptions of improved analytical procedures to track air pollution in major cities where the identification of the major sources will facilitate remediation measures (c) coordinated trials for radiation therapy of cervical cancer and the development of rigorous protocols (d) training of staff in research reactor operation and in the use of research reactors for the study of new materials. The participating countries have committed to reviewing the six existing sub-categories, namely (1) utilization of research reactors, (2,3) application of radiation and radioisotope in the agriculture and the medical fields, (4) public acceptance of nuclear energy, (5) radioactive waste management, and (6) nuclear safety culture. To share knowledge on human resources development within the region and to consider measures for the further development of human resources in relevant fields, a seminar for human resources development, sponsored by Japan, will be held in Japan. The conference will be renamed as (Forum for Nuclear Cooperation in Asia) beginning with the next conference. The Forum for Nuclear Cooperation in Asia will be held in Japan and in a participating country other than Japan in alternating years. To enhance the regional nuclear cooperation activities under this framework, each participating country will register a Coordinator and Project Leaders to facilitate

  9. Combgap Promotes Ovarian Niche Development and Chromatin Association of EcR-Binding Regions in BR-C.

    Directory of Open Access Journals (Sweden)

    Anna Hitrik

    2016-11-01

    Full Text Available The development of niches for tissue-specific stem cells is an important aspect of stem cell biology. Determination of niche size and niche numbers during organogenesis involves precise control of gene expression. How this is achieved in the context of a complex chromatin landscape is largely unknown. Here we show that the nuclear protein Combgap (Cg supports correct ovarian niche formation in Drosophila by controlling ecdysone-Receptor (EcR- mediated transcription and long-range chromatin contacts in the broad locus (BR-C. Both cg and BR-C promote ovarian growth and the development of niches for germ line stem cells. BR-C levels were lower when Combgap was either reduced or over-expressed, indicating an intricate regulation of the BR-C locus by Combgap. Polytene chromosome stains showed that Cg co-localizes with EcR, the major regulator of BR-C, at the BR-C locus and that EcR binding to chromatin was sensitive to changes in Cg levels. Proximity ligation assay indicated that the two proteins could reside in the same complex. Finally, chromatin conformation analysis revealed that EcR-bound regions within BR-C, which span ~30 KBs, contacted each other. Significantly, these contacts were stabilized in an ecdysone- and Combgap-dependent manner. Together, these results highlight Combgap as a novel regulator of chromatin structure that promotes transcription of ecdysone target genes and ovarian niche formation.

  10. Epigenetic Transgenerational Actions of Vinclozolin on Promoter Regions of the Sperm Epigenome

    Science.gov (United States)

    Guerrero-Bosagna, Carlos; Settles, Matthew; Lucker, Ben; Skinner, Michael K.

    2010-01-01

    Previous observations have demonstrated that embryonic exposure to the endocrine disruptor vinclozolin during gonadal sex determination promotes transgenerational adult onset disease such as male infertility, kidney disease, prostate disease, immune abnormalities and tumor development. The current study investigates genome-wide promoter DNA methylation alterations in the sperm of F3 generation rats whose F0 generation mother was exposed to vinclozolin. A methylated DNA immunoprecipitation with methyl-cytosine antibody followed by a promoter tilling microarray (MeDIP-Chip) procedure was used to identify 52 different regions with statistically significant altered methylation in the sperm promoter epigenome. Mass spectrometry bisulfite analysis was used to map the CpG DNA methylation and 16 differential DNA methylation regions were confirmed, while the remainder could not be analyzed due to bisulfite technical limitations. Analysis of these validated regions identified a consensus DNA sequence (motif) that associated with 75% of the promoters. Interestingly, only 16.8% of a random set of 125 promoters contained this motif. One candidate promoter (Fam111a) was found to be due to a copy number variation (CNV) and not a methylation change, suggesting initial alterations in the germline epigenome may promote genetic abnormalities such as induced CNV in later generations. This study identifies differential DNA methylation sites in promoter regions three generations after the initial exposure and identifies common genome features present in these regions. In addition to primary epimutations, a potential indirect genetic abnormality was identified, and both are postulated to be involved in the epigenetic transgenerational inheritance observed. This study confirms that an environmental agent has the ability to induce epigenetic transgenerational changes in the sperm epigenome. PMID:20927350

  11. Promoting ICT Entrepreneurship in the Campania Region of Italy: A Network of Academic Incubators

    Science.gov (United States)

    Corti, Eugenio; Torello, Rita Ilenia

    2004-01-01

    The government of the Campania region in southern Italy has established a technology transfer centre for the information and communications technology (ICT) sector. The Regional Centre for ICT Competencies (RCICT) promotes the transfer of ICT to local small and medium-sized enterprises (SMEs) and encourages the creation of new knowledge-based…

  12. Importance of a distal proximal contact on load transfer by implant-supported single adjacent crowns in posterior region of the mandible: a photoelastic study

    Science.gov (United States)

    de AGUIAR JÚNIOR, Fábio Afrânio; TIOSSI, Rodrigo; MACEDO, Ana Paula; de MATTOS, Maria da Gloria Chiarello; RIBEIRO, Ricardo Faria; RODRIGUES, Renata Cristina Silveira

    2013-01-01

    Objective This study aimed to evaluate the importance of a distal proximal contact on the load transfer to the posterior region of the mandible by non-splinted adjacent implant-supported crowns using photoelastic stress analysis. Material and Methods A rectangular model (68x30x15 mm) was made of polymethylmethacrylate resin to simulate half of the mandibular arch. One model was completed with resin replicas representing the first premolar and second molar and with two 3.75 mm dia.x11 mm internal hexagon threaded implants replacing the second premolar and first molar. The other model was manufactured in the same way but without the second molar. Both models were duplicated using photoelastic resin. The roots of the teeth replicas were covered with a layer of polyether impression material to simulate the periodontal ligament. Two different vertical loads were applied to the crowns as follows: 1 - single static point load alternately applied to the crowns replacing the second premolar and first molar (50 N); 2 - simultaneous static point loads applied to both of the crowns replacing the second premolar and first molar (100 N). The resulting isochromatic fringe pattern in the photoelastic model was monitored and photographed. Results All loading conditions studied showed that the presence of the second molar has changed the load transmission and the pattern of stresses. Conclusion Results showed that the presence of a second molar proximal contact can help minimize the stresses around the implants. PMID:24212984

  13. Importance of a distal proximal contact on load transfer by implant-supported single adjacent crowns in posterior region of the mandible: a photoelastic study

    Directory of Open Access Journals (Sweden)

    Fabio Afranio de Aguiar Junior

    2013-09-01

    Full Text Available OBJECTIVE: This study aimed to evaluate the importance of a distal proximal contact on the load transfer to the posterior region of the mandible by non-splinted adjacent implant-supported crowns using photoelastic stress analysis. MATERIAL AND METHODS: A rectangular model (68x30x15 mm was made of polymethylmethacrylate resin to simulate half of the mandibular arch. One model was completed with resin replicas representing the first premolar and second molar and with two 3.75 mm dia.x11 mm internal hexagon threaded implants replacing the second premolar and first molar. The other model was manufactured in the same way but without the second molar. Both models were duplicated using photoelastic resin. The roots of the teeth replicas were covered with a layer of polyether impression material to simulate the periodontal ligament. Two different vertical loads were applied to the crowns as follows: 1 - single static point load alternately applied to the crowns replacing the second premolar and first molar (50 N; 2 - simultaneous static point loads applied to both of the crowns replacing the second premolar and first molar (100 N. The resulting isochromatic fringe pattern in the photoelastic model was monitored and photographed. RESULTS: All loading conditions studied showed that the presence of the second molar has changed the load transmission and the pattern of stresses. CONCLUSION: Results showed that the presence of a second molar proximal contact can help minimize the stresses around the implants.

  14. Analysis of the mouse dhfr promoter region: existence of a divergently transcribed gene.

    Science.gov (United States)

    Crouse, G F; Leys, E J; McEwan, R N; Frayne, E G; Kellems, R E

    1985-01-01

    The use of murine dihydrofolate reductase (dhfr) gene amplification mutants enabled us to identify important structural and functional features of the dhfr promoter region. We found another transcription unit, at least 14 kilobases in size, which initiates within 130 base pairs of the major dhfr transcript and is transcribed divergently. The 5' ends of both transcripts were analyzed and found to have multiple initiation sites. The major dhfr transcript and the divergent transcript appear to share the same promoter region; the longer transcripts of the dhfr gene overlap with the divergent transcripts and use a different promoter region. The divergent transcript appears to code for a protein; an homologous sequence to its first exon is found in the corresponding location near the human dhfr gene. Images PMID:3018531

  15. Molecular cloning and functional characterization of the promoter region of the human uncoupling protein-2 gene.

    Science.gov (United States)

    Tu, N; Chen, H; Winnikes, U; Reinert, I; Marmann, G; Pirke, K M; Lentes, K U

    1999-11-19

    As a member of the uncoupling protein family, UCP2 is ubiquitously expressed in rodents and humans, implicating a major role in thermogenesis. To analyze promoter function and regulatory motifs involved in the transcriptional regulation of UCP2 gene expression, 3.3 kb of 5'-flanking region of the human UCP2 (hUCP2) gene have been cloned. Sequence analysis showed that the promoter region of hUCP2 lacks a classical TATA or CAAT box, however, appeared GC-rich resulting in the presence of several Sp-1 motifs and Ap-1/-2 binding sites near the transcription initiation site. Functional characterization of human UCP2 promoter-CAT fusion constructs in transient expression assays showed that minimal promoter activity was observed within 65 bp upstream of the transcriptional start site (+1). 75 bp further upstream (from nt -141 to -66) a strong cis-acting regulatory element (or enhancer) was identified, which significantly enhanced basal promoter activity. The regulation of human UCP2 gene expression involves complex interactions among positive and negative regulatory elements distributed over a minimum of 3.3 kb of the promoter region. Copyright 1999 Academic Press.

  16. The CD4 and CD3δε Cytosolic Juxtamembrane Regions Are Proximal within a Compact TCR-CD3-pMHC-CD4 Macrocomplex.

    Science.gov (United States)

    Glassman, Caleb R; Parrish, Heather L; Deshpande, Neha R; Kuhns, Michael S

    2016-06-01

    TCRs relay information about peptides embedded within MHC molecules (pMHC) to the ITAMs of the associated CD3γε, CD3δε, and CD3ζζ signaling modules. CD4 then recruits the Src kinase p56(Lck) (Lck) to the TCR-CD3 complex to phosphorylate the ITAMs, initiate intracellular signaling, and drive CD4(+) T cell fate decisions. Whereas the six ITAMs of CD3ζζ are key determinants of T cell development, activation, and the execution of effector functions, multiple models predict that CD4 recruits Lck proximal to the four ITAMs of the CD3 heterodimers. We tested these models by placing FRET probes at the cytosolic juxtamembrane regions of CD4 and the CD3 subunits to evaluate their relationship upon pMHC engagement in mouse cell lines. The data are consistent with a compact assembly in which CD4 is proximal to CD3δε, CD3ζζ resides behind the TCR, and CD3γε is offset from CD3δε. These results advance our understanding of the architecture of the TCR-CD3-pMHC-CD4 macrocomplex and point to regions of high CD4-Lck + ITAM concentrations therein. The findings thus have implications for TCR signaling, as phosphorylation of the CD3 ITAMs by CD4-associated Lck is important for CD4(+) T cell fate decisions. Copyright © 2016 by The American Association of Immunologists, Inc.

  17. Does FDI promote regional development? Evidence from local and regional productivity spillovers in Greece

    Directory of Open Access Journals (Sweden)

    Vassilis MONASTIRIOTIS

    2010-12-01

    Full Text Available Studies on the productivity spillovers of FDI have concentrated on the nationalsectoral level. As a result, little is known about the impact of FDI on absolute and relative regional economic performance. In this paper we examine this issue by relying on a unique dataset of over 20,000 Greek firms for the period 2002-2006 covering all sectors of economic activity. We examine the spatial distribution of foreign-owned firms in the country and analyse the effect that their presence – at the local, regional and national levels – has on the productivity of domestic firms. We find strong evidence suggesting that foreignowned firms self-select into regions and sectors of high productivity. Net of this selection effect, the impact of foreign presence on domestic productivity is negative – although at the very local level some positive spillover effects are identifiable. The bulk of the effects concentrate in non-manufacturing activities, high-tech sectors, and medium-sized high-productivity firms. Importantly, this effect is not constant across space however. Productivity spillovers tend to be negative in the regions hosting the main urban areas in the country but positive in smaller and more peripheral regions. In this way, despite the tendency of FDI to concentrate in a limited number of areas within the country – those of the highest level of development – the externalities that FDI activity generates to the local economies appear to be of a rather equilibrating character.

  18. A hybrid neural network system for prediction and recognition of promoter regions in human genome.

    Science.gov (United States)

    Chen, Chuan-Bo; Li, Tao

    2005-05-01

    This paper proposes a high specificity and sensitivity algorithm called PromPredictor for recognizing promoter regions in the human genome. PromPredictor extracts compositional features and CpG islands information from genomic sequence, feeding these features as input for a hybrid neural network system (HNN) and then applies the HNN for prediction. It combines a novel promoter recognition model, coding theory, feature selection and dimensionality reduction with machine learning algorithm. Evaluation on Human chromosome 22 was approximately 66% in sensitivity and approximately 48% in specificity. Comparison with two other systems revealed that our method had superior sensitivity and specificity in predicting promoter regions. PromPredictor is written in MATLAB and requires Matlab to run. PromPredictor is freely available at http://www.whtelecom.com/Prompredictor.htm.

  19. Preliminary Prioritization of California Oil and Gas Fields for Regional Groundwater Monitoring Based on Intensity of Petroleum Resource Development and Proximity to Groundwater Resources

    Science.gov (United States)

    Davis, T. A.; Landon, M. K.; Bennett, G.

    2016-12-01

    The California State Water Resources Control Board is collaborating with the U.S. Geological Survey to implement a Regional Monitoring Program (RMP) to assess where and to what degree groundwater resources may be at risk of contamination from oil and gas development activities including stimulation, well integrity issues, produced water ponds, and underground injection. A key issue in the implementation of the RMP is that the state has 487 onshore oil fields covering 8,785 square kilometers but detailed characterization work can only be done in a few oil fields annually. The first step in the RMP is to prioritize fields using available data that indicate potential risk to groundwater from oil and gas development, including vertical proximity of groundwater and oil/gas resources, density of petroleum and water wells, and volume of water injected in oil fields. This study compiled data for these factors, computed summary metrics for each oil field, analyzed statewide distributions of summary metrics, used those distributions to define relative categories of potential risk for each factor, and combined these into an overall priority ranking. Aggregated results categorized 22% (107 fields) of the total number of onshore oil and gas fields in California as high priority, 23% as moderate priority, and 55% as low priority. On an area-weighted basis, 41% of the fields ranked high, 30% moderate, and 29% low, highlighting that larger fields tend to have higher potential risk because of greater intensity of development, sometimes coupled with closer proximity to groundwater. More than half of the fields ranked as high priority were located in the southern Central Valley or the Los Angeles Basin. The prioritization does not represent an assessment of groundwater risk from oil and gas development; rather, such assessments are planned to follow based on detailed analysis of data from the RMP near the oil fields selected for study in the future.

  20. The system of Regional Contact Offices for promoting GMES services and the use of Space Technologies in European Regions.

    Science.gov (United States)

    Carrara, Paola; Antoninetti, Massimo; Bacai, Hina; Basoni, Anna; Bosc, Christelle; Clave, Magali; Cornacchia, Carmela; L'Astorina, Alba; Monbet, Philippe; Mueller, Bastian; Nicolau, Sonia; Pergola, Nicola; Rampini, Anna; Tramutoli, Valerio; Schumacher, Volker; Wells, Alan; Zepeda Juarez, Jesus; Zolotikova, Svetlana

    2013-04-01

    which have significant impact on the economy, environment and the quality of life of the citizens To this aim since 2011 the system of Regional Contact Offices (RCOs) was promoted by the EU FP7 DORIS_Net (Downsteam Observatory organized by Regions Active in Space - Network, http://www.doris-net.eu/) project as the regional link to the services provided by the European GMES programme. Since then a first nucleus of 12 pilot European Regions were working together establishing 6 first RCOs around Europe. This paper will present RCOs network goals, achievements and perspectives as well as its planned actions devoted to improve quality of Space Technology products from one side, to promote awareness and use of them by potential end-users (and particularly LRAs), from the other side.

  1. Australia's role in promoting and supporting tuberculosis control in the Western Pacific Region.

    Science.gov (United States)

    Shaw, Kerrie A

    2013-07-01

    Twenty-one percent of the world's tuberculosis cases are found in the Western Pacific Region. The region has demonstrated a lower rate of decline in incidence than the regions of Africa, the Americas and Europe. Issues around drug resistance, human immunodeficiency virus and diabetes impact on the burden of tuberculosis disease in the Western Pacific Region. Australia has exhibited a low and relatively stable tuberculosis incidence rate but has not progressed toward the desired international goal for tuberculosis elimination (globalisation and Australia's increasing economic and strategic engagement within the Western Pacific Region and South-East Asia. Promoting and supporting tuberculosis control within the Western Pacific Region provides an opportunity for Australia to maintain its low tuberculosis incidence rate and progress toward elimination.

  2. Organizational leadership and its relationship to regional health authority actions to promote health.

    Science.gov (United States)

    Barrett, Linda L; Plotnikoff, Ronald C; Raine, Kim

    2007-01-01

    The purpose of this paper is to examine organizational leadership and its relationship to regional health authority actions to promote health. Through use of four previously developed measures of Perceived Organizational Leadership for Health Promotion, this paper focused on leadership as a distributed entity within regional health authority (RHA) jurisdictions mandated to address the health of the population in the province of Alberta, Canada. First, examination of differentials between organizational levels (i.e. board members, n = 30; middle/senior management, n = 58; and service providers, n = 56) on ratings of the four leadership measures revealed significant differences. That is, board members tended to rate leadership components significantly higher than service providers and middle/senior managers: from across all 17 RHAs; and in low health promotion capacity and high health promotion capacity RHAs. Second, regression analyses identified that the leadership measures "Practices for Organizational Learning" and "Wellness Planning" were positively associated with health authority actions on improving population heart health (heart health promotion). The presence of a "Champion for Heart Health Promotion" and the leadership measures "Workplace Milieu" and "Organization Member Development" were also positively associated with health authority actions for health promotion. A subsidiary aim revealed low to moderate positive relationships of the dimensions of Leadership, Infrastructure and Will to Act with one another, as proposed by the Alberta Model on "Organizational Capacity Building for Health Promotion." This paper, conducted on the baseline dataset (n = 144) of the "Alberta Heart Health Project's Dissemination Phase", represents a rare effort to examine leadership at a collective organizational level.

  3. DNA Methylation Analysis of BRD1 Promoter Regions and the Schizophrenia rs138880 Risk Allele.

    Directory of Open Access Journals (Sweden)

    Mads Dyrvig

    Full Text Available The bromodomain containing 1 gene, BRD1 is essential for embryogenesis and CNS development. It encodes a protein that participates in histone modifying complexes and thereby regulates the expression of a large number of genes. Genetic variants in the BRD1 locus show association with schizophrenia and bipolar disorder and risk alleles in the promoter region correlate with reduced BRD1 expression. Insights into the transcriptional regulation of BRD1 and the pathogenic mechanisms associated with BRD1 risk variants, however, remain sparse. By studying transcripts in human HeLa and SH-SY5Y cells we provide evidence for differences in relative expression of BRD1 transcripts with three alternative 5' UTRs (exon 1C, 1B, and 1A. We further show that expression of these transcript variants covaries negatively with DNA methylation proportions in their upstream promoter regions suggesting that promoter usage might be regulated by DNA methylation. In line with findings that the risk allele of the rs138880 SNP in the BRD1 promoter region correlates with reduced BRD1 expression, we find that it is also associated with moderate regional BRD1 promoter hypermethylation in both adipose tissue and blood. Importantly, we demonstrate by inspecting available DNA methylation and expression data that these regions undergo changes in methylation during fetal brain development and that differences in their methylation proportions in fetal compared to postnatal frontal cortex correlate significantly with BRD1 expression. These findings suggest that BRD1 may be dysregulated in both the developing and mature brain of risk allele carriers. Finally, we demonstrate that commonly used mood stabilizers Lithium, Valproate, and Carbamazepine affect the expression of BRD1 in SH-SY5Y cells. Altogether this study indicates a link between genetic risk and epigenetic dysregulation of BRD1 which raises interesting perspectives for targeting the mechanisms pharmacologically.

  4. A Composite Method Based on Formal Grammar and DNA Structural Features in Detecting Human Polymerase II Promoter Region

    Science.gov (United States)

    Datta, Sutapa; Mukhopadhyay, Subhasis

    2013-01-01

    An important step in understanding gene regulation is to identify the promoter regions where the transcription factor binding takes place. Predicting a promoter region de novo has been a theoretical goal for many researchers for a long time. There exists a number of in silico methods to predict the promoter region de novo but most of these methods are still suffering from various shortcomings, a major one being the selection of appropriate features of promoter region distinguishing them from non-promoters. In this communication, we have proposed a new composite method that predicts promoter sequences based on the interrelationship between structural profiles of DNA and primary sequence elements of the promoter regions. We have shown that a Context Free Grammar (CFG) can formalize the relationships between different primary sequence features and by utilizing the CFG, we demonstrate that an efficient parser can be constructed for extracting these relationships from DNA sequences to distinguish the true promoter sequences from non-promoter sequences. Along with CFG, we have extracted the structural features of the promoter region to improve upon the efficiency of our prediction system. Extensive experiments performed on different datasets reveals that our method is effective in predicting promoter sequences on a genome-wide scale and performs satisfactorily as compared to other promoter prediction techniques. PMID:23437045

  5. A composite method based on formal grammar and DNA structural features in detecting human polymerase II promoter region.

    Directory of Open Access Journals (Sweden)

    Sutapa Datta

    Full Text Available An important step in understanding gene regulation is to identify the promoter regions where the transcription factor binding takes place. Predicting a promoter region de novo has been a theoretical goal for many researchers for a long time. There exists a number of in silico methods to predict the promoter region de novo but most of these methods are still suffering from various shortcomings, a major one being the selection of appropriate features of promoter region distinguishing them from non-promoters. In this communication, we have proposed a new composite method that predicts promoter sequences based on the interrelationship between structural profiles of DNA and primary sequence elements of the promoter regions. We have shown that a Context Free Grammar (CFG can formalize the relationships between different primary sequence features and by utilizing the CFG, we demonstrate that an efficient parser can be constructed for extracting these relationships from DNA sequences to distinguish the true promoter sequences from non-promoter sequences. Along with CFG, we have extracted the structural features of the promoter region to improve upon the efficiency of our prediction system. Extensive experiments performed on different datasets reveals that our method is effective in predicting promoter sequences on a genome-wide scale and performs satisfactorily as compared to other promoter prediction techniques.

  6. Functional characterization of a promoter region in the human MEN1 tumor suppressor gene.

    Science.gov (United States)

    Fromaget, Maud; Vercherat, Cécile; Zhang, Chang X; Zablewska, Barbara; Gaudray, Patrick; Chayvialle, Jean-Alain; Calender, Alain; Cordier-Bussat, Martine

    2003-10-10

    Our previous studies on the human MEN1 (multiple endocrine neoplasia type 1) gene revealed heterogeneity of MEN1 2.8 kb transcripts related to variation in their 5' UTR only. Six distinct exons 1 (e1A-e1F) were isolated that suggested the existence of multiple but not already identified transcriptional start sites (TSS) and of a complex transcriptional control. Identification of a minimal promoter region and its adjacent regulatory regions appears an inescapable step to the understanding of MEN1 gene transcriptional regulation in normal and pathological situations. For this purpose, we subcloned the approximately 2000 bp region situated directly upstream of the exon 2 in front of a luciferase reporter gene, and we analyzed functional consequences of 5' and 3' serial deletions, comparatively in a series of endocrine versus non-endocrine cell lines. Primer extension and RPA experiments demonstrate that in HEK293 cells transcription initiated simultaneously at several points in endogenous MEN1 promoter as well as in transfected promoter fragments in reporter plasmids, mainly in Inr elements that are efficiently employed to synthetize previously described exons e1A-e1D. Functional consequences of TSS deletion are directly related to cellular context. The minimal promoter region is localized between -135 and -36. Five large adjacent cis-regulatory regions (UR1-UR5) exist upstream of this minimal promoter region, whose activity depend not only on the cellular context but also on the presence of a downstream sequence DR1. Five small cis-regulatory elements (C1-C5) are localized between -325 and -107. Overexpression of exogenous menin, the MEN1 gene's product, in mouse embryonic fibroblasts from Men1(-/-) knock-out mice dose-dependently decreases MEN1 promoter activity, through sequences surrounding the minimal promoter. Our data highlight the existence of a complex transcriptional regulation of the MEN1 gene, whose activity is clearly modulated depending not only on the

  7. Regional differences in gene expression and promoter usage in aged human brains

    KAUST Repository

    Pardo, Luba M.

    2013-02-19

    To characterize the promoterome of caudate and putamen regions (striatum), frontal and temporal cortices, and hippocampi from aged human brains, we used high-throughput cap analysis of gene expression to profile the transcription start sites and to quantify the differences in gene expression across the 5 brain regions. We also analyzed the extent to which methylation influenced the observed expression profiles. We sequenced more than 71 million cap analysis of gene expression tags corresponding to 70,202 promoter regions and 16,888 genes. More than 7000 transcripts were differentially expressed, mainly because of differential alternative promoter usage. Unexpectedly, 7% of differentially expressed genes were neurodevelopmental transcription factors. Functional pathway analysis on the differentially expressed genes revealed an overrepresentation of several signaling pathways (e.g., fibroblast growth factor and wnt signaling) in hippocampus and striatum. We also found that although 73% of methylation signals mapped within genes, the influence of methylation on the expression profile was small. Our study underscores alternative promoter usage as an important mechanism for determining the regional differences in gene expression at old age.

  8. Brand Products of Regional Cuisine in the Promotion of Tourism in Roztocze

    Directory of Open Access Journals (Sweden)

    Bekier-Jaworska Ewa

    2015-03-01

    Full Text Available Introduction. There has been a trend over the last few years of using specialties of regional cuisine as an independent tourist attraction. The creation of local brands is an important element in the promotion of a given region and it also influences the development of culinary tourism. The aim of the studies conducted was to identify regional dishes - a choice of dishes that could be described as 'brand dishes' and the use of those dishes as tourist attractions in Roztocze. Material and methods. Studies were conducted on a group of students studying tourism and recreation at State Higher School of Vocational Education (PWSZ in Zamość using a questionnaire. Results. The questionnaire provided an assessment of the levels of knowledge of regional cuisine among Polish and Ukrainian students, identified the most characteristic dishes and selected brand products, and helped to arrive at a suitable method of promotion. Conclusions. Nationality, family customs and selection of local restaurants highly influence knowledge of regional cuisine. Interviewees decided that the most outstanding products from Roztocze were Zwierzyniec beer, and Biłgoraj pie. Regional products should be used as a tourist attraction in Roztocze.

  9. Isolation of a human anti-HIV gp41 membrane proximal region neutralizing antibody by antigen-specific single B cell sorting.

    Directory of Open Access Journals (Sweden)

    Lynn Morris

    Full Text Available Broadly neutralizing antibodies are not commonly produced in HIV-1 infected individuals nor by experimental HIV-1 vaccines. When these antibodies do occur, it is important to be able to isolate and characterize them to provide clues for vaccine design. CAP206 is a South African subtype C HIV-1-infected individual previously shown to have broadly neutralizing plasma antibodies targeting the envelope gp41 distal membrane proximal external region (MPER. We have now used a fluoresceinated peptide tetramer antigen with specific cell sorting to isolate a human neutralizing monoclonal antibody (mAb against the HIV-1 envelope gp41 MPER. The isolated recombinant mAb, CAP206-CH12, utilized a portion of the distal MPER (HXB2 amino acid residues, 673-680 and neutralized a subset of HIV-1 pseudoviruses sensitive to CAP206 plasma antibodies. Interestingly, this mAb was polyreactive and used the same germ-line variable heavy (V(H1-69 and variable kappa light chain (V(K3-20 gene families as the prototype broadly neutralizing anti-MPER mAb, 4E10 (residues 672-680. These data indicate that there are multiple immunogenic targets in the C-terminus of the MPER of HIV-1 gp41 envelope and suggests that gp41 neutralizing epitopes may interact with a restricted set of naive B cells during HIV-1 infection.

  10. Isolation of a Human Anti-HIV gp41 Membrane Proximal Region Neutralizing Antibody by Antigen-Specific Single B Cell Sorting

    Science.gov (United States)

    Morris, Lynn; Chen, Xi; Alam, Munir; Tomaras, Georgia; Zhang, Ruijun; Marshall, Dawn J.; Chen, Bing; Parks, Robert; Foulger, Andrew; Jaeger, Frederick; Donathan, Michele; Bilska, Mira; Gray, Elin S.; Abdool Karim, Salim S.; Kepler, Thomas B.; Whitesides, John; Montefiori, David; Moody, M. Anthony; Liao, Hua-Xin; Haynes, Barton F.

    2011-01-01

    Broadly neutralizing antibodies are not commonly produced in HIV-1 infected individuals nor by experimental HIV-1 vaccines. When these antibodies do occur, it is important to be able to isolate and characterize them to provide clues for vaccine design. CAP206 is a South African subtype C HIV-1-infected individual previously shown to have broadly neutralizing plasma antibodies targeting the envelope gp41 distal membrane proximal external region (MPER). We have now used a fluoresceinated peptide tetramer antigen with specific cell sorting to isolate a human neutralizing monoclonal antibody (mAb) against the HIV-1 envelope gp41 MPER. The isolated recombinant mAb, CAP206-CH12, utilized a portion of the distal MPER (HXB2 amino acid residues, 673–680) and neutralized a subset of HIV-1 pseudoviruses sensitive to CAP206 plasma antibodies. Interestingly, this mAb was polyreactive and used the same germ-line variable heavy (VH1-69) and variable kappa light chain (VK3-20) gene families as the prototype broadly neutralizing anti-MPER mAb, 4E10 (residues 672–680). These data indicate that there are multiple immunogenic targets in the C-terminus of the MPER of HIV-1 gp41 envelope and suggests that gp41 neutralizing epitopes may interact with a restricted set of naive B cells during HIV-1 infection. PMID:21980336

  11. Validation study of genes with hypermethylated promoter regions associated with prostate cancer recurrence.

    Science.gov (United States)

    Stott-Miller, Marni; Zhao, Shanshan; Wright, Jonathan L; Kolb, Suzanne; Bibikova, Marina; Klotzle, Brandy; Ostrander, Elaine A; Fan, Jian-Bing; Feng, Ziding; Stanford, Janet L

    2014-07-01

    One challenge in prostate cancer is distinguishing indolent from aggressive disease at diagnosis. DNA promoter hypermethylation is a frequent epigenetic event in prostate cancer, but few studies of DNA methylation in relation to features of more aggressive tumors or prostate cancer recurrence have been completed. We used the Infinium HumanMethylation450 BeadChip to assess DNA methylation in tumor tissue from 407 patients with clinically localized prostate cancer who underwent radical prostatectomy. Recurrence status was determined by follow-up patient surveys, medical record review, and linkage with the Surveillance, Epidemiology, and End Results (SEER) registry. The methylation status of 14 genes for which promoter hypermethylation was previously correlated with advanced disease or biochemical recurrence was evaluated. Average methylation level for promoter region CpGs in patients who recurred compared with those with no evidence of recurrence was analyzed. For two genes with differential methylation, time to recurrence was examined. During an average follow-up of 11.7 years, 104 (26%) patients recurred. Significant promoter hypermethylation in at least 50% of CpG sites in two genes, ABHD9 and HOXD3, was found in tumors from patients who recurred compared with those without recurrence. Evidence was strongest for HOXD3 (lowest P = 9.46 × 10(-6)), with higher average methylation across promoter region CpGs associated with reduced recurrence-free survival (P = 2 × 10(-4)). DNA methylation profiles did not differ by recurrence status for the other genes. These results validate the association between promoter hypermethylation of ADHB9 and HOXD3 and prostate cancer recurrence. Tumor DNA methylation profiling may help to distinguish patients with prostate cancer at higher risk for disease recurrence. ©2014 American Association for Cancer Research.

  12. Characterization of the promoter region of biosynthetic enzyme genes involved in berberine biosynthesis in Coptis japonica

    Directory of Open Access Journals (Sweden)

    Yasuyuki Yamada

    2016-09-01

    Full Text Available The presence of alkaloids is rather specific to certain plant species. However, berberine, an isoquinoline alkaloid, is relatively broadly distributed in the plant kingdom. Thus, berberine biosynthesis has been intensively investigated, especially using Coptis japonica cell cultures. Almost all biosynthetic enzyme genes have already been characterized at the molecular level. Particularly, two transcription factors (TFs, a plant-specific WRKY-type transcription factor, CjWRKY1, and a basic helix-loop-helix (bHLH transcription factor, CjbHLH1, were shown to comprehensively regulate berberine biosynthesis in C. japonica cells. In this study, we characterized the promoter region of some biosynthetic enzyme genes and associated cis-acting elements involved in the transcriptional regulation via two TFs. The promoter regions of three berberine biosynthetic enzyme genes (CYP80B2, 4’OMT and CYP719A1 were isolated, and their promoter activities were dissected by a transient assay involving the sequentially truncated promoter::luciferase (LUC reporter constructs. Furthermore, transactivation activities of CjWRKY1 were determined using the truncated promoter::LUC reporter constructs or constructs with mutated cis-elements. These results suggest the involvement of a putative W-box in the regulation of biosynthetic enzyme genes. Direct binding of CjWRKY1 to the W-box DNA sequence was also confirmed by an electrophoresis mobility shift assay (EMSA and by a chromatin immunoprecipitation (ChIP assay. In addition, CjbHLH1 also activated transcription from truncated 4’OMT and CYP719A1 promoters independently of CjWRKY1, suggesting the involvement of a putative E-box. Unexpected transcriptional activation of biosynthetic enzyme genes via a non-W-box sequence and by CjWRKY1 as well as the possible involvement of a GCC-box in berberine biosynthesis in C. japonica are discussed.

  13. [Nucleotide sequence of HLA-DQA1 promoter region (QAP) in a lung cancer patient].

    Science.gov (United States)

    Qiu, C; Zhou, W; Song, C

    1996-06-01

    The HLA-DQA1 allele and nucleotide sequence of HLA-DQA1 promoter region (QAP) in a patient with IDDM complicated lung cancer have been identified by PCR/SSCP, PCR/SSCP and PCR/sequencing. The results showed that: (1) All of the lung cancer patient and his family members carried HLA-DQA1* 0301/0501 alleles. (2) a single base substitution G-->A at position -155 and deletion CAA at position -161 to -163 occurred in the patient. These results suggest that the mutation of HLA-DQA1 promoter region may modulate HLA-DQA1 gene expression by trans-acting factors binding to variant cis-acting elements and may be responsible for pathogenesis of lung cancer.

  14. Structure of 5' region of human tenascin-R gene and characterization of its promoter.

    Science.gov (United States)

    Gherzi, R; Leprini, A; Siri, A; Zardi, L

    1998-03-01

    The tenascin-R (TN-R) gene encodes a multidomain extracellular matrix protein belonging to the tenascin family, previously detected only in the central nervous system. In this report, we describe the structure of the 5' region of the human TN-R gene and characterize the activity of its promoter. We cloned two previously unreported nontranslated exons (exons 1 and 2, 539 and 101 bp in length, respectively) separated by a large (> or = 40-kb) intron. The intron between exons 2 and 3 (containing the ATG codon) is 122 kb in length. Tenascin-R transcripts in fetal, adult, and neoplastic human brain contain both exons 1 and 2, as demonstrated by S1 nuclease analysis and reverse transcriptase-polymerase chain reaction. The human TN-R promoter displays relatively unusual features in terms of sequence in that it lacks any TATA box, CAAT box, GC-rich regions, or initiator element. The promoter displays its activity only in cultured cells of neural and glial origin, not in transformed epithelial cells and melanoma cells. All the elements required for the full and cell-specific activity of the promoter are contained in the 57-bp sequence closest to the transcription startpoint.

  15. Health promotion activities for elderly foreigners : a study about third sector organization and their health promotional activities for elderly foreigners in the Ostrobothnia region

    OpenAIRE

    Hägg, Jane; Zheng, Haixia

    2011-01-01

    The objective of this study is to find out the presence of available activities offered by the Third Sector Organizations for elderly from minorities in the Ostrobothnia Region. This study aims at raising awareness of health promotion and well-being. Therefore, the intention was to increase the knowledge and awareness about the Third Sector organizations and their health promotional activities in the Ostrobothnia Region. The qualitative method was used and the respondents have conducted se...

  16. VE-statin/egfl7 expression in endothelial cells is regulated by a distal enhancer and a proximal promoter under the direct control of Erg and GATA-2.

    Directory of Open Access Journals (Sweden)

    Alexandra Le Bras

    Full Text Available Angiogenesis is the process by which new blood vessels arise from existing ones by the budding out of endothelial cell capillaries from the luminal side of blood vessels. Blood vessel formation is essential for organ development during embryogenesis and is associated with several physiological and pathological processes, such as wound healing and tumor development. The VE-statin/egfl7 gene is specifically expressed in endothelial cells during embryonic development and in the adult. We studied here the regulatory mechanisms that control this tissue-specific expression. RT-qPCR analyses showed that the specificity of expression of VE-statin/egfl7 in endothelial cells is not shared with its closest neighbor genes notch1 and agpat2 on the mouse chromosome 2. Chromatin-immunoprecipitation analysis of histone modifications at the VE-statin/egfl7 locus showed that the chromatin is specifically opened in endothelial cells, but not in fibroblasts at the transcription start sites. A 13 kb genomic fragment of promoter was cloned and analyzed by gene reporter assays which showed that two conserved regions are important for the specific expression of VE-statin/egfl7 in endothelial cells; a -8409/-7563 enhancer and the -252/+38 region encompassing the exon-1b transcription start site. The latter contains essential GATA and ETS-binding sites, as assessed by linker-scanning analysis and site-directed mutagenesis. An analysis of expression of the ETS and GATA transcription factors showed that Erg, Fli-1 and GATA-2 are the most highly expressed factors in endothelial cells. Erg and GATA-2 directly control the expression of the endogenous VE-statin/egfl7 while Fli-1 probably exerts an indirect control, as assessed by RNA interference and chromatin immunoprecipitation. This first detailed analysis of the mechanisms that govern the expression of the VE-statin/egfl7 gene in endothelial cells pinpoints the specific importance of ETS and GATA factors in the specific

  17. Characterization of the human Glvr-1 phosphate transporter/retrovirus receptor gene and promoter region.

    Science.gov (United States)

    Palmer, G; Manen, D; Bonjour, J P; Caverzasio, J

    1999-01-08

    The cell surface receptor for gibbon ape leukemia virus (Glvr-1) belongs to the type III sodium-dependent phosphate transporter/retrovirus receptor gene family. Several observations have suggested an important role for Glvr-1 in regulated Pi handling in bone forming cells and prompted us to investigate further the molecular mechanisms regulating Glvr-1 gene expression. In addition, the regulation of Glvr-1 gene expression also has potential applications to gene therapy, since retroviral vectors carrying gibbon ape leukemia virus envelope proteins are used for gene delivery into different cell types. The aim of this study was thus to clone the human Glvr-1 gene in order to describe its structure and its promoter region. Our results indicate that the Glvr-1 gene consists of 11 exons and 10 introns spread over 18kb of genomic DNA. The translation initiation site is located within exon II and the translation stop codon within exon XI. Rapid amplification of cDNA ends (5'-RACE) suggests that, in human SaOS-2 osteoblast-like cells, transcription of Glvr-1 is initiated at multiple sites, mostly located between bp 32 and 50 of the published cDNA sequence, which was initially obtained from HL-60 cells. The 5'-flanking region of the gene is characterized by a very high GC content. Reporter gene assays demonstrate the presence of a functional promoter upstream of exon I and indicate that a GC-rich region, containing two potential SP1 binding sites, is required for high promoter activity in transiently transfected SaOS-2 cells. The description of the human Glvr-1 gene structure, as well as the analysis of some structural and functional characteristics of its promoter region, provide a basis for more detailed investigation of the molecular mechanisms controlling expression of the Glvr-1 gene in bone forming cells and in other cell types.

  18. Proximal femoral fractures

    DEFF Research Database (Denmark)

    Palm, Henrik; Teixidor, Jordi

    2015-01-01

    -displaced femoral neck fractures and prosthesis for displaced among the elderly; and sliding hip screw for stabile- and intramedullary nails for unstable- and sub-trochanteric fractures) but they are based on a variety of criteria and definitions - and often leave wide space for the individual surgeons' subjective...... guidelines for hip fracture surgery and discuss a method for future pathway/guideline implementation and evaluation. METHODS: By a PubMed search in March 2015 six studies of surgical treatment pathways covering all types of proximal femoral fractures with publication after 1995 were identified. Also we...... searched the homepages of the national heath authorities and national orthopedic societies in West Europe and found 11 national or regional (in case of no national) guidelines including any type of proximal femoral fracture surgery. RESULTS: Pathway consensus is outspread (internal fixation for un...

  19. Footprinting the 'essential regulatory region' of the retinoblastoma gene promoter in intact human cells.

    Science.gov (United States)

    Temple, Mark D; Murray, Vincent

    2005-03-01

    The retinoblastoma tumour suppressor protein is a key cell cycle regulator. Protein-DNA interactions at the retinoblastoma (RB1) promoter, including the 'essential regulatory region', were investigated using novel DNA-targeted nitrogen mustards in intact human cells. The footprinting experiments were carried out in two different environments: in intact HeLa and K562 cells where the access of DNA-targeted probes to chromatin is affected by cellular protein-DNA interactions associated with gene regulation; and in purified DNA where their access is unencumbered by protein-DNA interactions. Using the ligation-mediated PCR (LMPCR) technique, the sites of damage were determined at base pair resolution on DNA sequencing gels. Our results demonstrate that, in intact cells, footprints were observed at the E2F, ATF and RBF1/Sp1 DNA binding motifs in the RB1 promoter. In addition, a novel footprint was observed at a previously unidentified cycle homology region (CHR) and at four uncharacterised protein-DNA binding sites. In further experiments, nitrogen mustard-treated cells were FACS sorted into G1, S and G2/M phases of the cell cycle prior to LMPCR analysis. Expression of the RB1 gene is cell cycle-regulated and footprinting studies of the promoter in FACS-sorted cells indicated that transcription factor binding at the GC box, CHR binding motif and the 'essential regulatory region' are cell cycle dependent.

  20. Association of polymorphisms in the promoter region of turkey prolactin with egg performance

    Directory of Open Access Journals (Sweden)

    Fathi Mehrangiz

    2014-01-01

    Full Text Available The induction and regulation of broodiness is of the most important role of prolactin in avian species. In this study, the association between prolactin promoter region alleles and reproductive traits in Fars native turkey was investigated. These traits consisted of mean egg weight (MEW, number of egg (EN and egg mass, during the first laying period. In total, 115 laying turkeys, randomly selected from the flock of the Breeding Center for Fars Native turkey, and DNA was purificated from blood samples, 231 bp of prolactin promoter region was amplified and Genotype of Samples was determinate by PCR-SSCP technique were genotyped. Two alleles D and I were identified. Based on the results obtained, the frequency of D and I alleles were 0.67 and 0.33, respectively. Frequencies of DD, II and ID genotypes were 0.385, 0.044 and 0.571, respectively. The association analysis between the polymorphism PRL gene promoter region and egg performance was carried out. Significant relationship was found between genotypes with egg production (P<0.01. Individuals with II genotype produced higher egg production than DD and ID genotype. The results of current study showed that using information of genes related to egg production could be used to improve the performance of native turkey of East Azerbaijan province.

  1. 5-Hydroxy tryptamine transporter (5HTT) gene promoter region polymorphism in anxiety and depressive disorders.

    Science.gov (United States)

    Mushtaq, Raheel; Shoib, Sheikh; Shah, Tabindah; Mushtaq, Sahil

    2014-01-01

    5HTTLPR polymorphism (5- Hydroxy tryptamine transporter linked promoter region polymorphism) is the most widely studied genetic variant in psychiatry. The present study is a modest effort at ascertaining the role of 5HT transporter linked promoter region polymorphism (5HTTLPR) in anxiety and depressive disorders in Kashmir (India).The aim of this study was to examine 5-Hydroxy tryptamine transporter (5HTT) gene promoter region polymorphism in anxiety and depressive disorders. Thirty patients with unipolar depressive disorders, 30 patients with anxiety disorders and 40 healthy volunteers (controls) were studied on a case control design, using polymerase chain reaction (PCR) and agarose gel electrophoresis after digestion with endonuclease enzyme. Genotypes and allele frequencies were compared using chi square tests, and p value of 0.05). The genetic studies are still evolving as pathogenesis of anxiety and depressive disorders and involve the interaction of environmental factors with various genes. Genetic variation in different populations and hence different environments is important for elucidation of the mechanisms of these disorders. However, the study concludes that the locus under study is not shared between the two disorders.

  2. Discovery and Evaluation of Polymorphisms in the and Promoter Regions for Risk of Korean Lung Cancer

    Directory of Open Access Journals (Sweden)

    Jae Sook Sung

    2012-09-01

    Full Text Available AKT is a signal transduction protein that plays a central role in the tumorigenesis. There are 3 mammalian isoforms of this serine/threonine protein kinase-AKT1, AKT2, and AKT3-showing a broad tissue distribution. We first discovered 2 novel polymorphisms (AKT2 -9826 C/G and AKT3 -811 A/G, and we confirmed 6 known polymorphisms (AKT2 -9473 C/T, AKT2 -9151 C/T, AKT2 -9025 C/T, AKT2 -8618G/A, AKT3 -675 A/-, and AKT3 -244 C/T of the AKT2 and AKT3 promoter region in 24 blood samples of Korean lung cancer patients using direct sequencing. To evaluate the role of AKT2 and AKT3 polymorphisms in the risk of Korean lung cancer, genotypes of the AKT2 and AKT3 polymorphisms (AKT2 -9826 C/G, AKT2 -9473 C/T, AKT2 -9151 C/T, AKT2 -9025 C/T, AKT2 -8618G/A, and AKT3 -675 A/- were determined in 360 lung cancer patients and 360 normal controls. Statistical analyses revealed that the genotypes and haplotypes in the AKT2 and AKT3 promoter regions were not significantly associated with the risk of lung cancer in the Korean population. These results suggest that polymorphisms of the AKT2 and AKT3 promoter regions do not contribute to the genetic susceptibility to lung cancer in the Korean population.

  3. A protein binding AT-rich sequence in the soybean leghemoglobin c3 promoter is a general cis element that requires proximal DNA elements to stimulate transcription

    DEFF Research Database (Denmark)

    Laursen, N B; Larsen, K; Knudsen, J Y

    1994-01-01

    A nodule nuclear factor, NAT2, interacts with two AT-rich binding sites (NAT2 BS1 and NAT2 BS2) in the soybean leghemoglobin (lb) c3 promoter. In transgenic Lotus corniculatus nodules, an oligonucleotide containing NAT2 BS1 activated an inactive -159 lbc3 promoter when placed immediately upstream...

  4. Proximal renal tubular acidosis

    Science.gov (United States)

    Renal tubular acidosis - proximal; Type II RTA; RTA - proximal; Renal tubular acidosis type II ... by alkaline substances, mainly bicarbonate. Proximal renal tubular acidosis (Type II RTA) occurs when bicarbonate is not ...

  5. Governmental promotion of the Information Society in the Spanish Region of Valencia

    Directory of Open Access Journals (Sweden)

    Emilio Feliu-García, Ph.D.

    2011-01-01

    Full Text Available Regional spheres are considered essential in the governmental promotion of the Information Society at the international level. The regional initiatives in Spain aim to strengthen and complement the initiatives promoted at the national level. This article analyses ICT penetration in the Valencian Community from 1996 to 2008. The objective is to identify which of the actions carried out by the Valencian Regional Government have had a positive effect on its society.The methodology employed in this study is benchmarking. The selection of indicators is based on the policies evaluation model proposed in the Plan Avanza (Spain’s national Information Society strategy. Data were collected from official statistical sources (like Spain’s National Statistics Institute, INE. Three statistical tests were applied to verify the hypotheses (Pearson’s r2, Chi-square and Student’s t.The results indicate that it is not possible to affirm that the actions implemented by the Valencian Regional Government have had a more positive effect on its society than those implemented by the Spanish Central Government. A reason for this may lie in the specific objectives of the political strategy implemented by the Valencian Government, which has focused primarily on e-Government and does not include enough projects centred on the implementation of new technologies in the private sector. Moreover, the integration of new technologies in everyday life is placed in a second level of importance despite citizens are central actors in the international agenda.

  6. L1CAM expression in endometrial carcinomas is regulated by usage of two different promoter regions

    Directory of Open Access Journals (Sweden)

    Pfeifer Marco

    2010-08-01

    Full Text Available Abstract Background The L1 cell adhesion molecule (L1CAM was originally identified as a neural adhesion molecule involved in axon guidance. In many human epithelial carcinomas L1CAM is overexpressed and thereby augments cell motility, invasion and metastasis formation. L1CAM positive carcinomas are associated with bad prognosis. Recent data point out that L1CAM is regulated in a fashion similar to epithelial-mesenchymal transition (EMT. Previous studies have implied the transcription factors Slug and/or β-catenin in L1CAM transcriptional regulation. However, the regulation of human L1CAM expression at the transcriptional level is not well understood. Results To better understand the molecular basis of L1CAM transcriptional regulation, we carried out a detailed characterization of the human L1CAM promoter. We identified two transcription start sites, the first in front of a non-translated exon 0 (promoter 1 and the other next to the first protein-coding exon 1 (promoter 2. Both sites could be verified in endometrial carcinoma (EC cell lines and appear to be used in a cell-type specific manner. The two identified promoter regions showed activity in luciferase reporter assays. Chromatin-IP analyses confirmed the in silico predicted E-boxes, binding sites for transcription factors Snail and Slug, as well as Lef-1 sites, which are related to β-catenin-mediated transcriptional regulation, in both promoters. Overexpression of β-catenin exclusively augmented activity of promoter 1 whereas Slug enhanced promoter 1 and 2 activity suggesting that both promoters can be active. Overexpression of β-catenin or Slug could upregulate L1CAM expression in a cell-type specific manner. Conclusions Our results, for the first time, provide evidence that the L1CAM gene has two functionally active promoter sites that are used in a cell-type specific manner. Slug and β-catenin are involved L1CAM transcriptional regulation. Nevertheless, Slug rather than

  7. Promoting Collaboration in Jabodetabekjur: A Learning Regions Perspective on Knowledge-Based Economy

    Directory of Open Access Journals (Sweden)

    Muhammad Rahmat Yananda

    2017-06-01

    regional cooperation; (4 unalignment with the national urban development strategies; and (5 loss of momentum in KBE development. Learning regions can be constructed by analyzing a path or trajectories combined with the potentials of the urban region elements (Academicians, Businesses, Communities and Governments. They can also be constructed via governance approach and development of appropriate organizational models. City’s administrations should take active roles as the initiator of the collaboration process opted by certain types and activities. Strategy and policy – making related to collaboration gave rise to: (1 KBE development themes; (2 vision/ mission statements; and (3 principles of engagement and capacities. Resources gaps were found and can be applied as inputs to build joint projects, namely: (1 incubation and innovation centers; and (2 product innovation promotion center.

  8. Calreticulin discriminates the proximal region at the N-glycosylation site of Glc1Man9GlcNAc2 ligand

    Energy Technology Data Exchange (ETDEWEB)

    Hirano, Makoto; Adachi, Yuka [Department of Materials and Life Science, Seikei University, 3-3-1 Kichijoji-kita, Musashino, Tokyo 180-8633 (Japan); Ito, Yukishige [Synthetic Cellular Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); ERATO, Japan Science and Technology Agency, Ito Glycotrilogy Project, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Totani, Kiichiro, E-mail: ktotani@st.seikei.ac.jp [Department of Materials and Life Science, Seikei University, 3-3-1 Kichijoji-kita, Musashino, Tokyo 180-8633 (Japan)

    2015-10-23

    Calreticulin (CRT) is well known as a lectin-like chaperone that recognizes Glc1Man9GlcNAc2 (G1M9)-glycoproteins in the endoplasmic reticulum (ER). However, whether CRT can directly interact with the aglycone moiety (protein portion) of the glycoprotein remains controversial. To improve our understanding of CRT interactions, structure-defined G1M9-derivatives with different aglycones (–OH, –Gly–NH{sub 2}, and –Gly–Glu–{sup t}Bu) were used as CRT ligands, and their interactions with recombinant CRT were analyzed using thermal shift analysis. The results showed that CRT binds strongly to a G1M9-ligand in the order –Gly–Glu–{sup t}Bu > –Gly–NH{sub 2} > –OH, which is the same as that of the reglucosylation of Man9GlcNAc2 (M9)-derivatives by the folding sensor enzyme UGGT (UDP-glucose: glycoprotein glucosyltransferase). Our results indicate that, similar to UGGT, CRT discriminates the proximal region at the N-glycosylation site, suggesting a similar mechanism mediating the recognition of aglycone moieties in the ER glycoprotein quality control system. - Highlights: • Glc1Man9GlcNAc2 (G1M9) ligands with different aglycones were chemically prepared. • Calreticulin (CRT) discriminates the aglycone of Glc1Man9GlcNAc2 (G1M9) ligand. • CRT binds with G1M9 ligands in a similar manner to folding sensor enzyme.

  9. Humoral Immunogenicity of an HIV-1 Envelope Residue 649-684 Membrane-proximal Region Peptide Fused to the Plague Antigen F1-V

    Science.gov (United States)

    Matoba, Nobuyuki; Shah, Namrata Rahul; Mor, Tsafrir S

    2011-01-01

    The membrane-proximal region spanning residues 649-684 of the HIV-1 envelope protein gp41 (MPR649-684) is an attractive vaccine target for humoral immunity that blocks viral transcytosis across the mucosal epithelia. However, induction of high-titer MPR649-684-specific antibodies remains a challenging task. To explore potential solutions for this challenge, we tested a new translational fusion protein comprising the plague F1-V antigen and MPR649-684 (F1-V-MPR649-684). We employed systemic immunization for initial feasibility analyses. Despite strong immunogenicity demonstrated for the immunogen, repeated systemic immunizations of mice with F1-V-MPR649-684 hardly induced MPR649-684-specific IgG. In contrast, a single immunization with F1-V-MPR649-684 mounted a significant anti-MPR649-684 IgG response in animals that were primed with another MPR649-684 fusion protein based on the cholera toxin B subunit. Additional boost immunizations with F1-V-MPR649-684 recalled and maintained the antibody response and expanded the number of specific antibody-secreting B cells. Thus, while F1-V-MPR649-684 alone was not sufficiently immunogenic to induce detectable levels of MPR649-684-specific antibodies, these results suggest that prime-boost immunization using heterologous antigen-display platforms may overcome the poor humoral immunogenicity of MPR649-684 for the induction of durable humoral immunity. Further studies are warranted to evaluate the feasibility of this strategy in mucosal immunization. Lastly, our findings add to a growing body of evidence in support of this strategy for immunogen design for poorly immunogenic epitopes besides the MPR of HIV-1's transmembrane envelope protein. PMID:21693158

  10. Transcytosis-blocking abs elicited by an oligomeric immunogen based on the membrane proximal region of HIV-1 gp41 target non-neutralizing epitopes.

    Science.gov (United States)

    Matoba, Nobuyuki; Griffin, Tagan A; Mittman, Michele; Doran, Jeffrey D; Alfsen, Annette; Montefiori, David C; Hanson, Carl V; Bomsel, Morgane; Mor, Tsafrir S

    2008-05-01

    CTB-MPR(649-684), a translational fusion protein consisting of cholera toxin B subunit (CTB) and residues 649 684 of gp41 membrane proximal region (MPR), is a candidate vaccine aimed at blocking early steps of HIV-1 mucosal transmission. Bacterially produced CTB MPR(649-684) was purified to homogeneity by two affinity chromatography steps. Similar to gp41 and derivatives thereof, the MPR domain can specifically and reversibly self-associate. The affinities of the broadly-neutralizing monoclonal Abs 4E10 and 2F5 to CTB MPR(649-684) were equivalent to their nanomolar affinities toward an MPR peptide. The fusion protein's affinity to GM1 ganglioside was comparable to that of native CTB. Rabbits immunized with CTB-MPR(649-684) raised only a modest level of anti-MPR(649-684) Abs. However, a prime-boost immunization with CTB-MPR(649-684) and a second MPR(649-684)-based immunogen elicited a more productive anti-MPR(649-684) antibody response. These Abs strongly blocked the epithelial transcytosis of a primary subtype B HIV-1 isolate in a human tight epithelial model, expanding our previously reported results using a clade D virus. The Abs recognized epitopes at the N-terminal portion of the MPR peptide, away from the 2F5 and 4E10 epitopes and were not effective in neutralizing infection of CD4+ cells. These results indicate distinct vulnerabilities of two separate interactions of HIV-1 with human cells - Abs against the C-terminal portion of the MPR can neutralize CD4+-dependent infection, while Abs targeting the MPR's N-terminal portion can effectively block galactosyl ceramide dependent transcytosis. We propose that Abs induced by MPR(649-684)-based immunogens may provide broad protective value independent of infection neutralization.

  11. ECRbase: Database of Evolutionary Conserved Regions, Promoters, and Transcription Factor Binding Sites in Vertebrate Genomes

    Energy Technology Data Exchange (ETDEWEB)

    Loots, G; Ovcharenko, I

    2006-08-08

    Evolutionary conservation of DNA sequences provides a tool for the identification of functional elements in genomes. We have created a database of evolutionary conserved regions (ECRs) in vertebrate genomes entitled ECRbase that is constructed from a collection of pairwise vertebrate genome alignments produced by the ECR Browser database. ECRbase features a database of syntenic blocks that recapitulate the evolution of rearrangements in vertebrates and a collection of promoters in all vertebrate genomes presented in the database. The database also contains a collection of annotated transcription factor binding sites (TFBS) in all ECRs and promoter elements. ECRbase currently includes human, rhesus macaque, dog, opossum, rat, mouse, chicken, frog, zebrafish, and two pufferfish genomes. It is freely accessible at http://ECRbase.dcode.org.

  12. Influence of an educational strategy to promote the use of regional food

    Directory of Open Access Journals (Sweden)

    Mariana Cavalcante Martins

    2015-05-01

    Full Text Available Objective: to assess the knowledge, attitude and practice of family members of preschool children about regional food, through a survey before and after an educational intervention. Methods: this is a pre-experimental one-group pretest–posttest study, with 62 family members of preschool children. One month before and after the conduction of an educational activity using the flipchart “regional food promoting food security”, one applied the survey. Results: it was found that after the educational strategy, there was an increase in the classification “appropriate” in each survey area about regional food, and the variation of knowledge (17.7%-77.4%, attitude (21%-72.6% and practice (14.5%-64.5%, consequently, an improvement of 59.7% in knowledge, 51.6% in attitude and 50% in practice. Conclusion: the use of educational technology had a positive influence on the knowledge, attitudes and practice of family members, contributing thus to the health promotion of children and their family members.

  13. Structural features of DNA are conserved in the promoter region of orthologous genes across different strains of Helicobacter pylori.

    Science.gov (United States)

    Kumar, Aditya; Manivelan, Vasumathi; Bansal, Manju

    2016-09-01

    Promoter regions play a key role in the process of transcription initiation and gene expression, hence promoter identification is an inherent component of the genome annotation process. Identification and characterization of promoters in fully sequenced genomes is a challenging and complex task. An analysis of sequence-dependent DNA structural properties in the promoter region of orthologous and non-orthologous genes can help in characterizing promoters and also provide insights into transcription initiation. Various structural properties, such as duplex stability, protein-induced bendability and intrinsic curvature of promoter sequences have been calculated and compared for 10 different strains of Helicobacter pylori genomes, and it is found that promoter regions in orthologous and non-orthologous genes show distinct trends for these properties, with orthologous genes showing sharper low-stability peak, lower bendability and higher curvature. The average GC content of orthologous genes is higher than that of non-orthologous genes, and relative stability-based promoter annotation tool PromPredict performs better for orthologous genes than non-orthologous genes. The characteristic sequence-dependent structural properties of promoters show significant differences between orthologous and non-orthologous genes. Interestingly, these structural properties of promoters are conserved, but the genes themselves vary in their evolutionary selection rate. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Genomic analysis of the chromosome 15q11-q13 Prader-Willi syndrome region and characterization of transcripts for GOLGA8E and WHCD1L1 from the proximal breakpoint region

    Directory of Open Access Journals (Sweden)

    Kashork Catherine D

    2008-01-01

    Full Text Available Abstract Background Prader-Willi syndrome (PWS is a neurobehavioral disorder characterized by neonatal hypotonia, childhood obesity, dysmorphic features, hypogonadism, mental retardation, and behavioral problems. Although PWS is most often caused by a paternal interstitial deletion of a 6-Mb region of chromosome 15q11-q13, the identity of the exact protein coding or noncoding RNAs whose deficiency produces the PWS phenotype is uncertain. There are also reports describing a PWS-like phenotype in a subset of patients with full mutations in the FMR1 (fragile X mental retardation 1 gene. Taking advantage of the human genome sequence, we have performed extensive sequence analysis and molecular studies for the PWS candidate region. Results We have characterized transcripts for the first time for two UCSC Genome Browser predicted protein-coding genes, GOLGA8E (golgin subfamily a, 8E and WHDC1L1 (WAS protein homology region containing 1-like 1 and have further characterized two previously reported genes, CYF1P1 and NIPA2; all four genes are in the region close to the proximal/centromeric deletion breakpoint (BP1. GOLGA8E belongs to the golgin subfamily of coiled-coil proteins associated with the Golgi apparatus. Six out of 16 golgin subfamily proteins in the human genome have been mapped in the chromosome 15q11-q13 and 15q24-q26 regions. We have also identified more than 38 copies of GOLGA8E-like sequence in the 15q11-q14 and 15q23-q26 regions which supports the presence of a GOLGA8E-associated low copy repeat (LCR. Analysis of the 15q11-q13 region by PFGE also revealed a polymorphic region between BP1 and BP2. WHDC1L1 is a novel gene with similarity to mouse Whdc1 (WAS protein homology region 2 domain containing 1 and human JMY protein (junction-mediating and regulatory protein. Expression analysis of cultured human cells and brain tissues from PWS patients indicates that CYFIP1 and NIPA2 are biallelically expressed. However, we were not able to

  15. Promoter regions of potato vacuolar invertase gene in response to sugars and hormones.

    Science.gov (United States)

    Ou, Yongbin; Song, Botao; Liu, Xun; Xie, Conghua; Li, Meng; Lin, Yuan; Zhang, Huiling; Liu, Jun

    2013-08-01

    Potato vacuolar acid invertase (StvacINV1) (β-fructofuranosidase; EC 3.2.1.26) has been confirmed to play an important role in cold-induced sweetening of potato tubers. However, the transcriptional regulation mechanisms of StvacINV1 are largely unknown. In this study, the 5'-flanking sequence of StvacINV1 was cloned and the cis-acting elements were predicted. Histochemical assay showed that the StvacINV1 promoter governed β-glucuronidase (GUS) expression in potato leaves, stems, roots and tubers. Quantitative analysis of GUS expression suggested that the activity of StvacINV1 promoter was suppressed by sucrose, glucose, fructose, and cold, while enhanced by indole-3-acetic acid (IAA), and gibberellic acid (GA3). Further deletion analysis clarified that the promoter regions from -118 to -551, -551 to -1021, and -1021 to -1521 were required for responding to sucrose/glucose, GA3, and IAA, respectively. These findings provide essential information regarding transcriptional regulation mechanisms of StvacINV1. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  16. Promotion of Social Entrepreneurship Through Public Services in the Madrid Region: Succesful Aspects

    Directory of Open Access Journals (Sweden)

    M. Teresa Fernández Fernández

    2012-11-01

    Full Text Available This article analyzes the promotion of social entrepreneurship through the delivery of services in public business incubators in the Madrid region. The research is innovative since the implication of the public sector in boosting social entrepreneurship is quite new in Spain. Methodology starts with a literature revision of the factors conforming social entrepreneurship and focuses on networking. Then, social entrepreneurship presence and its promotion is analyzed both in the practices and services provided by the Madrid Development Agency in its “Madrid Emprende” incubation program and also through a survey addressed to the 113 firms hosted in its network of business incubators. Results of the survey show that social entrepreneurship is present as the main purpose of their activity in a majority of the firms, in their social products and services, in their social legal form supported by the public network and in some forms of public-private partnership promoted by the Madrid Business Incubators Network. Services provided by the public network show the quality, the added value and the know-how of the practices of the public program and have an impact in the efficient performance of the firms regarding social entrepreneurship and in the public-private alliances established for some social purposes.

  17. Entrepreneurialism and health-promoting retail food environments in Canadian city-regions.

    Science.gov (United States)

    Mah, Catherine L; Hasdell, Rebecca; Minaker, Leia M; Soo, Stephanie D; Cook, Brian; Demaio, Alessandro R

    2017-09-02

    The retail sector is a dynamic and challenging component of contemporary food systems with an important influence on population health and nutrition. Global consensus is clear that policy and environmental changes in retail food environments are essential to promote healthier diets and reduce the burden of obesity and non-communicable diseases. In this article, we explore entrepreneurialism as a form of social change-making within retail food environments, focusing on small food businesses. Small businesses face structural barriers within food systems. However, conceptual work in multiple disciplines and evidence from promising health interventions tested in small stores suggest that these retail places may have a dual role in health promotion: settings to strengthen regional economies and social networks, and consumer environments to support healthier diets. We will discuss empirical examples of health-promoting entrepreneurialism based on two sets of in-depth interviews we conducted with public health intervention actors in Toronto, Canada, and food entrepreneurs and city-region policy actors in St. John's, Canada. We will explore the practices of entrepreneurialism in the retail food environment and examine the implications for population health interventions. We contend that entrepreneurialism is important to understand on its own and also as a dimension of population health intervention context. A growing social scientific literature offers a multifaceted lens through which we might consider entrepreneurialism not only as a set of personal characteristics but also as a practice in networked and intersectoral cooperation for public and population health. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. The ftsQ1p gearbox promoter of Escherichia coli is a major sigma S-dependent promoter in the ddlB-ftsA region.

    Science.gov (United States)

    Ballesteros, M; Kusano, S; Ishihama, A; Vicente, M

    1998-10-01

    The most potent promoters in the ddlB-ftsA region of the dcw cluster have been analysed for sigmaS-dependent transcription. Only the gearbox promoter ftsQ1p was found to be transcribed in vitro by RNA polymerase holoenzyme coupled to sigmaS (EsigmaS). This dependency on sigmaS was also found in vivo when single-copy fusions to a reporter gene were analysed in rpoS and rpoS+ backgrounds. Although ftsQ1p can be transcribed by RNA polymerase containing either sigmaD or sigmaS, there is a preference for EsigmaS when the assay conditions include potassium glutamate and supercoiled templates, a property shared with the bolA1p gearbox promoter. The rest of the promoters assayed, ftsQ2p and ftsZ2p3p4p, similarly to the control bolA2p promoter, were preferentially transcribed by EsigmaD, the housekeeper polymerase. The ftsQ1p and the bolA1p promoters also share the presence of AT-rich sequences upstream of the - 35 region and the requirement for an intact wild-type alpha-subunit for a proficient transcription, allowing their joint classification as gearboxes.

  19. The role of COMESA in promoting intra-regional agricultural trade: Case study of Sudan

    Directory of Open Access Journals (Sweden)

    Azharia Abdelbagi Elbushra

    2011-06-01

    Full Text Available African countries have created many regional trade agreements with the economic objectives of reducing trade barriers and encouraging economic growth. The COMESA is an example of regional integration singed on 1993 by 19 African countries including Sudan. COMESA represents a chance for member countries to enhance their economic and social relations through increasing intra-trade. The objective of this paper is to assess the role of COMESA in promoting intra-regional agricultural trade between Sudan and COMESA countries. A multi-market model with Armington non-linear specification was applied. The paper results showed that there is a great potential for Sudan to increase its agricultural exports to other COMESA countries. The domestic agricultural markets are expected to be hampered by imports surge and increase in competition, while the producers of agricultural export commodities will be better off. In order to compete and benefit from potential in the COMESA markets, the paper recommended improving efficiency in the Sudanese agricultural sector through increasing productivity, lowering cost of production, enhancing marketing services, attaining economies of scale and attracting foreign investment.

  20. Proximity sensor technology for manipulator end effectors

    Science.gov (United States)

    Johnston, A. R.

    1975-01-01

    Optical proximity sensing techniques which could be used to help control the critical grasping phase of a remote manipulation are described. The proximity sensors described use a triangulation geometry to detect a surface located in a pre-determined region. The design of the proximity sensors themselves is discussed, as well as their application to manipulator control with a local control loop, and possibilities for future development are discussed.

  1. Helicobacter pylori cagA Promoter Region Sequences Influence CagA Expression and Interleukin 8 Secretion.

    Science.gov (United States)

    Ferreira, Rui M; Pinto-Ribeiro, Ines; Wen, Xiaogang; Marcos-Pinto, Ricardo; Dinis-Ribeiro, Mário; Carneiro, Fátima; Figueiredo, Ceu

    2016-02-15

    Heterogeneity at the Helicobacter pylori cagA gene promoter region has been linked to variation in CagA expression and gastric histopathology. Here, we characterized the cagA promoter and expression in 46 H. pylori strains from Portugal. Our results confirm the relationship between cagA promoter region variation and protein expression originally observed in strains from Colombia. We observed that individuals with intestinal metaplasia were all infected with H. pylori strains containing a specific cagA motif. Additionally, we provided novel functional evidence that strain-specific sequences in the cagA promoter region and CagA expression levels influence interleukin 8 secretion by the host gastric epithelial cells. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  2. [Social participation and health promotion: a case study in the region of Paranapiacaba and Parque Andreense].

    Science.gov (United States)

    Silva, Elaine Cristina da; Pelicioni, Maria Cecília Focesi

    2013-02-01

    Community participation is considered a key condition for communities to assume control of their health within the scope of health promotion. This study sought to identify and analyze the perceptions of residents of the watershed areas of Santo André/São Paulo with respect to the actions of health education and environmental education developed by the public authorities of the city, and how the local community participates in these processes. Data collection was conducted via structured and semi-structured interviews with civil servants and local residents. The methodology of content analysis proposed by Bardin was used for data interpretation. The main results showed that the health measures developed in the region studied are still predominantly viewed from the standpoint of prevention and not as an educational process able to support and achieve some of the goals of health promotion, such as the development of personal skills and support for community action. Data analysis showed the importance of intersectorial activity and conducting emancipatory educational measures as a key factor for participative procedures and the empowerment of the population.

  3. Promoting discovery and access to real time observations produced by regional coastal ocean observing systems

    Science.gov (United States)

    Anderson, D. M.; Snowden, D. P.; Bochenek, R.; Bickel, A.

    2015-12-01

    In the U.S. coastal waters, a network of eleven regional coastal ocean observing systems support real-time coastal and ocean observing. The platforms supported and variables acquired are diverse, ranging from current sensing high frequency (HF) radar to autonomous gliders. The system incorporates data produced by other networks and experimental systems, further increasing the breadth of the collection. Strategies promoted by the U.S. Integrated Ocean Observing System (IOOS) ensure these data are not lost at sea. Every data set deserves a description. ISO and FGDC compliant metadata enables catalog interoperability and record-sharing. Extensive use of netCDF with the Climate and Forecast convention (identifying both metadata and a structured format) is shown to be a powerful strategy to promote discovery, interoperability, and re-use of the data. To integrate specialized data which are often obscure, quality control protocols are being developed to homogenize the QC and make these data more integrate-able. Data Assembly Centers have been established to integrate some specialized streams including gliders, animal telemetry, and HF radar. Subsets of data that are ingested into the National Data Buoy Center are also routed to the Global Telecommunications System (GTS) of the World Meteorological Organization to assure wide international distribution. From the GTS, data are assimilated into now-cast and forecast models, fed to other observing systems, and used to support observation-based decision making such as forecasts, warnings, and alerts. For a few years apps were a popular way to deliver these real-time data streams to phones and tablets. Responsive and adaptive web sites are an emerging flexible strategy to provide access to the regional coastal ocean observations.

  4. Polymorphism in the promoter region of von Willebrand factor gene and von Willebrand disease type 1

    Directory of Open Access Journals (Sweden)

    Daniel Simon

    2003-12-01

    Full Text Available The -1185A/G polymorphism in the 5'-regulatory region of the von Willebrand factor (VWF gene was associated with VWF plasma levels in a normal population. This study was undertaken to evaluate whether there is a relationship between this polymorphism and type 1 von Willebrand disease (VWD, a disorder characterized by a quantitative deficiency of VWF. The association between this polymorphism and plasma VWF levels in normal Brazilian individuals was also analyzed. Control subjects (n = 460 and type 1 VWD patients (n = 41 were studied. Polymerase chain reaction (PCR amplification of the 864-bp VWF promoter region followed by AccII restriction-digestion was used to identify the -1185A/G genotypes. The -1185G allele frequency was 57% in normal individuals and 63% in type 1 VWD patients, this difference was not significant (p = 0.29. No significant association was observed between -1185A/G genotypes and VWF plasma levels in normal individuals, although VWF levels were in the same direction as those reported by another study, with subjects carrying the G allele having the lower levels. These results suggest that -1185A/G polymorphism is not associated with the partial deficiency of VWF in type 1 VWD patients.

  5. A 5'-regulatory region and two coding region polymorphisms modulate promoter activity and gene expression of the growth suppressor gene ZBED6 in cattle.

    Directory of Open Access Journals (Sweden)

    Yong-Zhen Huang

    Full Text Available Zinc finger, BED-type containing 6 (ZBED6 is an important transcription factor in placental mammals, affecting development, cell proliferation and growth. Polymorphisms in its promoter and coding regions are likely to impact ZBED6 transcription and growth traits. In this study, rapid amplification of 5' cDNA ends (5'-RACE analysis revealed two transcription start sites (TSS for the bovine ZBED6 starting within exon 1 of the ZC3H11A gene (TSS-1 and upstream of the translation start codon of the ZBED6 gene (TSS-2. There was one SNP in the promoter and two missense mutations in the coding region of the bovine ZBED6 by sequencing of the pooled DNA samples (Pool-Seq, n = 100. The promoter and coding region are the key regions for gene function; polymorphisms in these regions can alter gene expression. Quantitative real-time PCR (qPCR analysis showed that ZBED6 has a broad tissue distribution in cattle and is highly expressed in skeletal muscle. Eleven promoter-detection vectors were constructed, which enabled the cloning of putative promoter sequences and analysis of ZBED6 transcriptional activity by luciferase reporter gene assays. The core region of the basal promoter of bovine ZBED6 is located within region -866 to -556. The activity of WT-826G-pGL3 in driving reporter gene transcription is significantly higher than that of the M-826A-pGL3 construct (P < 0.01. Analysis of gene expression patterns in homozygous full-sibling Chinese Qinchuan cattle showed that the mutant-type Hap-AGG exhibited a lower mRNA level than the wild-type Hap-GCA (P < 0.05 in longissimus dorsi muscle (LDM. Moreover, ZBED6 mRNA expression was low in C2C12 cells overexpressing the mutant-type ZBED6 (pcDNA3.1(+-Hap-GG (P < 0.01. Our results suggest that the polymorphisms in the promoter and coding regions may modulate the promoter activity and gene expression of bovine ZBED6 in the skeletal muscles of these cattle breeds.

  6. Mutational analysis of the promoter and the coding region of the 5-HT1A gene

    Energy Technology Data Exchange (ETDEWEB)

    Erdmann, J.; Noethen, M.M.; Shimron-Abarbanell, D. [Univ. of Bonn (Germany)] [and others

    1994-09-01

    Disturbances of serotonergic pathways have been implicated in many neuropsychiatric disorders. Serotonin (5HT) receptors can be subdivided into at least three major families (5HT1, 5HT2, and 5HT3). Five human 5HT1 receptor subtypes have been cloned, namely 1A, 1D{alpha}, 1D{beta}, 1E, and 1F. Of these, the 5HT1A receptor is the best characterized subtype. In the present study we sought to identify genetic variation in the 5HT1A receptor gene which through alteration of protein function or level of expression might contribute to the genetics of neuropsychiatric diseases. The coding region and the 5{prime} promoter region of the 5HT1A gene from 159 unrelated subjects (45 schizophrenic, 46 bipolar affective, and 43 patients with Tourette`s syndrome, as well as 25 controls) were analyzed using SSCA. SSCA revealed the presence of two mutations both located in the coding region of the 5HT1A receptor gene. The first mutation is a rare silent C{r_arrow}T substitution at nucleotide position 549. The second mutation is characterized by a base pair substitution (A{r_arrow}G) at the first position of codon 28 and results in an amino acid exchange (Ile{r_arrow}Val). Since Val28 was found only in a single schizophrenic patient and in none of the other patients or controls, we decided to extend our samples and to use a restriction assay for screening a further 74 schizophrenic, 95 bipolar affective, and 49 patients with Tourette`s syndrome, as well as 185 controls, for the presence of the mutation. In total, the mutation was found in 2 schizophrenic patients, in 3 bipolars, in 1 Tourette patient, and in 5 controls. To our knowledge the Ile-28-Val substitution reported here is the first natural occuring molecular variant which has been identified for a serotonin receptor so far.

  7. Public health and health promotion capacity at national and regional level: a review of conceptual frameworks

    Directory of Open Access Journals (Sweden)

    Christoph Aluttis

    2014-04-01

    Full Text Available The concept of capacity building for public health has gained much attention during the last decade. National as well as international organizations increasingly focus their efforts on capacity building to improve performance in the health sector. During the past two decades, a variety of conceptual frameworks have been developed which describe relevant dimensions for public health capacity. Notably, these frameworks differ in design and conceptualization. This paper therefore reviews the existing conceptual frameworks and integrates them into one framework, which contains the most relevant dimensions for public health capacity at the country or regional level. A comprehensive literature search was performed to identify frameworks addressing public health capacity building at the national or regional level. We content-analysed these frameworks to identify the core dimensions of public health capacity. The dimensions were subsequently synthesized into a set of thematic areas to construct a conceptual framework which describes the most relevant dimensions for capacities at the national or regional level. The systematic review resulted in the identification of seven core domains for public health capacity: resources, organizational structures, workforce, partnerships, leadership and governance, knowledge development and country specific context. Accordingly, these dimensions were used to construct a framework, which describes these core domains more in detail. Our research shows that although there is no generally agreed upon model of public health capacity, a number of key domains for public health and health promotion capacity are consistently recurring in existing frameworks, regardless of their geographical location or thematic area. As only little work on the core concepts of public health capacities has yet taken place, this study adds value to the discourse by identifying these consistencies across existing frameworks and by synthesising

  8. MAGNETIC RESONANCE IMAGING, GROSS POSTMORTEM, AND HISTOLOGICAL FINDINGS FOR SOFT TISSUES OF THE PLANTAR ASPECT OF THE TARSUS AND PROXIMAL METATARSAL REGION IN NON-LAME HORSES.

    Science.gov (United States)

    Dyson, Sue; Blunden, Anthony; Murray, Rachel

    2017-03-01

    Injuries of the plantar soft tissues of the tarsus and proximal metatarsus can be a source of lameness in horses, however published information is lacking on high field MRI characteristics of these tissues. Objectives of the current anatomic study were to (1) describe high-field MRI features of the plantar tarsal and proximal metatarsal soft tissues; and (2) compare MRI findings with gross and histological appearances of selected structures for a sample of cadaver limbs from non-lame horses. Single hindlimbs for 42 horses, and right and left hindlimbs for eight horses were scanned using high-field MRI. The MRI findings were described for the 50 single limbs; and the MRI, gross postmortem and histological findings were compared for the eight pairs of hindlimbs. The superficial digital flexor tendon had uniform low signal intensity, surrounded by the flexor retinaculum of intermediate to high signal intensity on all sequences. The lateral digital flexor tendon had slightly higher signal intensity, enclosed on the plantaromedial aspects by the low signal intensity metatarsocalcaneal ligament. The accessory ligament of the deep digital flexor tendon varied in size and signal intensity. The proximal and distal plantar ligaments, accessory ligament of the suspensory ligament, and calcaneoquartal ligament had low signal intensity. The long plantar ligament comprised a number of related parts, separated by lines of high signal intensity corresponding with fibrous septae seen in gross anatomical specimens. The plantar aspect of the ligament had uniform low signal intensity in all sequences, but the dorsal half was more heterogeneous with multifocal spots or lines of higher signal intensity. © 2016 American College of Veterinary Radiology.

  9. Selection for Unequal Densities of Sigma70 Promoter-like Signalsin Different Regions of Large Bacterial Genomes

    Energy Technology Data Exchange (ETDEWEB)

    Huerta, Araceli M.; Francino, M. Pilar; Morett, Enrique; Collado-Vides, Julio

    2006-03-01

    The evolutionary processes operating in the DNA regions that participate in the regulation of gene expression are poorly understood. In Escherichia coli, we have established a sequence pattern that distinguishes regulatory from nonregulatory regions. The density of promoter-like sequences, that are recognizable by RNA polymerase and may function as potential promoters, is high within regulatory regions, in contrast to coding regions and regions located between convergently-transcribed genes. Moreover, functional promoter sites identified experimentally are often found in the subregions of highest density of promoter-like signals, even when individual sites with higher binding affinity for RNA polymerase exist elsewhere within the regulatory region. In order to investigate the generality of this pattern, we have used position weight matrices describing the -35 and -10 promoter boxes of E. coli to search for these motifs in 43 additional genomes belonging to most established bacterial phyla, after specific calibration of the matrices according to the base composition of the noncoding regions of each genome. We have found that all bacterial species analyzed contain similar promoter-like motifs, and that, in most cases, these motifs follow the same genomic distribution observed in E. coli. Differential densities between regulatory and nonregulatory regions are detectable in most bacterial genomes, with the exception of those that have experienced evolutionary extreme genome reduction. Thus, the phylogenetic distribution of this pattern mirrors that of genes and other genomic features that require weak selection to be effective in order to persist. On this basis, we suggest that the loss of differential densities in the reduced genomes of host-restricted pathogens and symbionts is the outcome of a process of genome degradation resulting from the decreased efficiency of purifying selection in highly structured small populations. This implies that the differential

  10. Multiset proximity spaces

    Directory of Open Access Journals (Sweden)

    A. Kandil

    2016-10-01

    Full Text Available A multiset is a collection of objects in which repetition of elements is essential. This paper is an attempt to explore the theoretical aspects of multiset by extending the notions of compact, proximity relation and proximal neighborhood to the multiset context. Examples of new multiset topologies, open multiset cover, compact multiset and many identities involving the concept of multiset have been introduced. Further, an integral examples of multiset proximity relations are obtained. A multiset topology induced by a multiset proximity relation on a multiset M has been presented. Also the concept of multiset δ- neighborhood in the multiset proximity space which furnishes an alternative approach to the study of multiset proximity spaces has been mentioned. Finally, some results on this new approach have been obtained and one of the most important results is: every T4- multiset space is semi-compatible with multiset proximity relation δ on M (Theorem 5.10.

  11. Analysis of the Impact of the Flow of Migrant Workers on Regional Economy: Based on the Thought about the Promotion of Jiangxi Regional Economic Competitiveness

    OpenAIRE

    Sun Yuping

    2016-01-01

    Labor resource is the necessary productive factor in regional economic development, and one of important indexes to evaluate regional economic competitiveness. The great economic achievement brought by the 30-year reform and opening up of China is due to the fact that China brought the backward advantage of “demographic dividend” into play, promoted the fast development of industrialization and urbanization, and became the second largest economy in the world. The entity of “demographic divide...

  12. Evidence of young, proximal and primary (YPP diamond source occurring in alluviums in the Santo Antônio do Bonito, Santo Inácio and Douradinho rivers in Coromandel region, Minas Gerais

    Directory of Open Access Journals (Sweden)

    Rogério Silvestre Pereira

    Full Text Available ABSTRACT: Magmatism associated with the Alto Paranaíba structural high comprises kimberlites, kamafugites, and alkaline complexes, forming an approximately 400 x 150 km NW-SE belt in the southern São Francisco Craton. Dating of some intrusions reveals ages between 120 and 75 Ma. Chemical analyses of garnet recovered in alluvium from traditional diamond digging areas indicate peridotitic garnet windows in Três Ranchos and Coromandel. Six hundred and eighty (680 diamonds acquired or recovered during mineral exploration in the digging areas of Romaria, Estrela do Sul, Três Ranchos and Coromandel show unique characteristics, certain populations indicating young, proximal and primary sources (YPP. Analyses of 201 stones from Santo Antônio do Bonito, Santo Inácio and Douradinho rivers alluvium, Coromandel, present no evidence of transport, characterizing a proximal source. Within these river basins, exposures of the Late Cretaceous Capacete Formation basal conglomerate contain mainly small rounded and/or angular quartzite pebbles and of basic and ultrabasic rocks, as well as kimberlite minerals (garnet, ilmenite, spinel, sometimes diamond. A magnetotelluric profile between the Paraná and Sanfranciscana basins shows that the thick underlying lithosphere in the Coromandel region coincides with the peridotitic garnet window and with a diamond population displaying proximal source characteristics. Diamond-bearing kimberlite intrusions occur in different areas of Alto Paranaíba.

  13. Geoheritage promotion of Thonon-les-Bains (Fr) region by the development of a geotourism product

    Science.gov (United States)

    Fanguin, Pauline

    2014-05-01

    Since 2012, the Chablais region (only in France) has acquired the Geopark label. This Geopark contributes to sustainable economic development of the region through geotourism. Moreover, the three Chablais (figure 1) are concerned by an Interreg IV program since 2009 (program of cooperation between European countries). The main objective of this program is to enhance the heritage resources (nature, culture and lifestyle of the region) (www.interreg-francesuisse.org). Therefore, the geotourism offer in this area just waiting to expand. The geodidactics models like the simplification of the scientific content are essential for geoheritage promotion, because this content must be available to a wide audience, allowing thereby the geoheritage recognition. The geotourism permits to apply different models (Cayla et al. 2010, Sellier, 2009) through a wide range of geotourism products, like guide, educational panels, thematic hikes and recently developed, new medias (website, smartphone applications). A geotourism product is based on four areas of questioning and was developed by Martin et al. (2010): (1) site (choice of sites to be valued), (2) public (a family public, good example of heterogeneous public), (3) contents (reasoning on geodidactics models) and (4) support (smartphone application). These four areas are very fundamental before the creation of any geotourism product. These reflexions aim to obtain a mediation product that integrates into geotourism offer of a region and contributes to its development and meets public expectations. New media, such as digital media - smartphone, tablets, website - become geotourism products more and more attractive. In addition, the necessary technologies to develop new media help to integrate a high interactivity potential with the public and thus get their attention. The architecture of this geotourism product is based on the new application developed by the Institute of Geography and sustainability, and the Bureau Relief. One

  14. Gel shift analysis of the empA promoter region in Vibrio anguillarum

    Directory of Open Access Journals (Sweden)

    Denkin Steven M

    2004-10-01

    Full Text Available Abstract Background The induction of metalloprotease encoded by empA in Vibrio anguillarum occurs at high cell density in salmon intestinal mucus. Previously we have shown that there are significant differences in empA expression in two strains of V. anguillarum, M93Sm and NB10. It is hypothesized that differences in empA regulation are due to differences in binding of regulatory elements. Results Two strains of V. anguillarum, M93Sm and NB10, were examined and compared for the presence of DNA regulatory proteins that bind to and control the empA promoter region. Gel mobility shift assays, using a digoxigenin (DIG-labeled oligomer containing a lux box-like element and the promoter for empA, were done to demonstrate the presence of a DNA-binding protein. Protein extracts from NB10 cells incubated in Luria Bertani broth + 2% NaCl (LB20, nine salts solution + 200 μg/ml mucus (NSSM, 3M (marine minimal medium, or NSS resulted in a gel mobility shift. No gel mobility shift was seen when protein extracts from either LB20- or NSSM-grown M93Sm cells were mixed with the DIG-labeled empA oligomer. The azocasein assay detected protease activity in all incubation conditions for NB10 culture supernatants. In contrast, protease activity was detected in M93Sm culture supernatants only when incubated in NSSM. Since the luxR homologue in V. anguillarum, vanT, has been cloned, sequenced, and shown to be required for protease activity, we wanted to determine if vanT mutants of NB10 exhibit the same gel shift observed in the wild-type. Site-directed mutagenesis was used to create vanT mutants in V. anguillarum M93Sm and NB10 to test whether VanT is involved with the gel mobility shift. Both vanT mutants, M02 and NB02, did not produce protease activity in any conditions. However, protein extracts from NB02 incubated in each condition still exhibited a gel shift when mixed with the DIG-labeled empA oligomer. Conclusions The data demonstrate that protein extracts of V

  15. A public health approach to promoting advance care planning to Aboriginal people in regional communities.

    Science.gov (United States)

    Sinclair, Craig; Williams, Glenda; Knight, Andrew; Auret, Kirsten

    2014-02-01

    To explore perceptions of Noongar community members towards advance care planning (ACP), while developing culturally appropriate information resources for use in community and hospital settings. Qualitative research methods, combining active health promotion with interviews and group discussions for participant feedback. Six rural communities across the Great Southern region of Western Australia. Eighteen Noongar community members consented to participate in interviews or group discussions. Community members received information about ACP at community events or home visits, from an Aboriginal health worker and palliative care researcher. Semi-structured interviews and group discussions were thematically analysed using a descriptive, exploratory approach. Research team reflections on community events also constituted data. Key themes impacting on perceptions of ACP included cultural approaches to dying, importance of family and kin, and appropriate communication. Participants were satisfied with the information resource and method of community engagement. Culturally appropriate methods of engaging Aboriginal people in ACP discussions should include Aboriginal health workers and take a whole of community approach to awareness raising. © 2014 The Authors. Australian Journal of Rural Health © National Rural Health Alliance Inc.

  16. Zero expiratory pressure and low oxygen concentration promote heterogeneity of regional ventilation and lung densities.

    Science.gov (United States)

    Borges, J B; Porra, L; Pellegrini, M; Tannoia, A; Derosa, S; Larsson, A; Bayat, S; Perchiazzi, G; Hedenstierna, G

    2016-08-01

    It is not well known what is the main mechanism causing lung heterogeneity in healthy lungs under mechanical ventilation. We aimed to investigate the mechanisms causing heterogeneity of regional ventilation and parenchymal densities in healthy lungs under anesthesia and mechanical ventilation. In a small animal model, synchrotron imaging was used to measure lung aeration and regional-specific ventilation (sV̇). Heterogeneity of ventilation was calculated as the coefficient of variation in sV̇ (CVsV̇ ). The coefficient of variation in lung densities (CVD ) was calculated for all lung tissue, and within hyperinflated, normally and poorly aerated areas. Three conditions were studied: zero end-expiratory pressure (ZEEP) and FI O2 0.21; ZEEP and FI O2 1.0; PEEP 12 cmH2 O and FI O2 1.0 (Open Lung-PEEP = OLP). The mean tissue density at OLP was lower than ZEEP-1.0 and ZEEP-0.21. There were larger subregions with low sV̇ and poor aeration at ZEEP-0.21 than at OLP: 12.9 ± 9.0 vs. 0.6 ± 0.4% in the non-dependent level, and 17.5 ± 8.2 vs. 0.4 ± 0.1% in the dependent one (P = 0.041). The CVsV̇ of the total imaged lung at PEEP 12 cmH2 O was significantly lower than on ZEEP, regardless of FI O2 , indicating more heterogeneity of ventilation during ZEEP (0.23 ± 0.03 vs. 0.54 ± 0.37, P = 0.049). CVD changed over the different mechanical ventilation settings (P = 0.011); predominantly, CVD increased during ZEEP. The spatial distribution of the CVD calculated for the poorly aerated density category changed with the mechanical ventilation settings, increasing in the dependent level during ZEEP. ZEEP together with low FI O2 promoted heterogeneity of ventilation and lung tissue densities, fostering a greater amount of airway closure and ventilation inhomogeneities in poorly aerated regions. © 2016 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.

  17. Regional Differences in Correlates of Daily Walking among Middle Age and Older Australian Rural Adults: Implications for Health Promotion.

    Science.gov (United States)

    Dollman, James; Hull, Melissa; Lewis, Nicole; Carroll, Suzanne; Zarnowiecki, Dorota

    2016-01-08

    Rural Australians are less physically active than their metropolitan counterparts, and yet very little is known of the candidate intervention targets for promoting physical activity in rural populations. As rural regions are economically, socially and environmentally diverse, drivers of regular physical activity are likely to vary between regions. This study explored the region-specific correlates of daily walking among middle age and older adults in rural regions with contrasting dominant primary industries. Participants were recruited through print and electronic media, primary care settings and community organisations. Pedometers were worn by 153 adults for at least four days, including a weekend day. A questionnaire identified potential intra-personal, social and environmental correlates of physical activity, according to a social ecological framework. Regression modelling identified independent correlates of daily walking separately in the two study regions. In one region, there were independent correlates of walking from all levels of the social ecological framework. In the other region, significant correlates of daily walking were almost all demographic (age, education and marital status). Participants living alone were less likely to be physically active regardless of region. This study highlights the importance of considering region-specific factors when designing strategies for promoting regular walking among rural adults.

  18. Regional Differences in Correlates of Daily Walking among Middle Age and Older Australian Rural Adults: Implications for Health Promotion

    Directory of Open Access Journals (Sweden)

    James Dollman

    2016-01-01

    Full Text Available Rural Australians are less physically active than their metropolitan counterparts, and yet very little is known of the candidate intervention targets for promoting physical activity in rural populations. As rural regions are economically, socially and environmentally diverse, drivers of regular physical activity are likely to vary between regions. This study explored the region-specific correlates of daily walking among middle age and older adults in rural regions with contrasting dominant primary industries. Participants were recruited through print and electronic media, primary care settings and community organisations. Pedometers were worn by 153 adults for at least four days, including a weekend day. A questionnaire identified potential intra-personal, social and environmental correlates of physical activity, according to a social ecological framework. Regression modelling identified independent correlates of daily walking separately in the two study regions. In one region, there were independent correlates of walking from all levels of the social ecological framework. In the other region, significant correlates of daily walking were almost all demographic (age, education and marital status. Participants living alone were less likely to be physically active regardless of region. This study highlights the importance of considering region-specific factors when designing strategies for promoting regular walking among rural adults.

  19. Proximal Probes Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Proximal Probes Facility consists of laboratories for microscopy, spectroscopy, and probing of nanostructured materials and their functional properties. At the...

  20. Isolation and characterization of a polyubiquitin gene and its promoter region from Mesembryanthemum crystallinum.

    Science.gov (United States)

    Azad, Muhammad Abul Kalam; Morita, Kunio; Ohnishi, Jun-ichi; Kore-eda, Shin

    2013-01-01

    Transcript levels of the polyubiquitin gene McUBI1 had been reported to be constant during Crassulacean acid metabolism (CAM) induction in the facultative CAM plant, Mesembryanthemum crystallinum. Here, we report the sequences of the full-length cDNA of McUBI1 and its promoter, and validation of the McUBI1 promoter as an internal control driving constitutive expression in transient assays using the dual-luciferase system to investigate the regulation of CAM-related gene expression. The McUBI1 promoter drove strong, constitutive expression during CAM induction. We compared the activities of this promoter with those of the cauliflower mosaic virus (CaMV) 35S promoter in detached C3- and CAM-performing M. crystallinum and tobacco leaves. We confirmed stable expression of the genes controlled by the McUBI1 promoter with far less variability than under the CaMV 35S promoter in M. crystallinum, whereas both promoters worked well in tobacco. We found the McUBI1 promoter more suitable than the CaMV 35S promoter as an internal control for transient expression assays in M. crystallinum.

  1. Regulatory elements in the promoter region of the rat gene encoding the acyl-CoA-binding protein

    DEFF Research Database (Denmark)

    Elholm, M; Bjerking, G; Knudsen, J

    1996-01-01

    Acyl-CoA-binding protein (ACBP) is an ubiquitously expressed 10-kDa protein which is present in high amounts in cells involved in solute transport or secretion. Rat ACBP is encoded by a gene containing the typical hallmarks of a housekeeping gene. Analysis of the promoter region of the rat ACBP g...

  2. Gene Expression in Archaea: Studies of Transcriptional Promoters, Messenger RNA Processing, and Five Prime Untranslated Regions in "Methanocaldococcus Jannashchii"

    Science.gov (United States)

    Zhang, Jian

    2009-01-01

    Gene expression in Archaea is less understood than those in Bacteria and Eucarya. In general, three steps are involved in gene expression--transcription, RNA processing, and translation. To expand our knowledge of these processes in Archaea, I have studied transcriptional promoters, messenger RNA processing, and 5'-untranslated regions in…

  3. TdaA Regulates Tropodithietic Acid Synthesis by Binding to the tdaC Promoter Region ▿ †

    OpenAIRE

    Geng, Haifeng; Belas, Robert

    2011-01-01

    Silicibacter sp. TM1040, a member of the marine Roseobacter clade, produces the antibiotic and quorum signaling molecule tropodithietic acid (TDA), encoded by tdaABCDEF. Here, we showed that an LysR-type transcriptional regulator, TdaA, is a positive regulator of tdaCDE gene expression and binds to the tdaC promoter region.

  4. Promoter proximal polyadenylation sites reduce transcription activity

    DEFF Research Database (Denmark)

    Andersen, Pia Kjølhede; Lykke-Andersen, Søren; Jensen, Torben Heick

    2012-01-01

    Gene expression relies on the functional communication between mRNA processing and transcription. We previously described the negative impact of a point-mutated splice donor (SD) site on transcription. Here we demonstrate that this mutation activates an upstream cryptic polyadenylation (CpA) site......, which in turn causes reduced transcription. Functional depletion of U1 snRNP in the context of the wild-type SD triggers the same CpA event accompanied by decreased RNA levels. Thus, in accordance with recent findings, U1 snRNP can shield premature pA sites. The negative impact of unshielded pA sites...... RNA polymerase II-transcribed genes use specialized termination mechanisms to maintain high transcription levels....

  5. Public health and health promotion capacity at national and regional level: a review of conceptual frameworks.

    Science.gov (United States)

    Aluttis, Christoph; den Broucke, Stephan Van; Chiotan, Cristina; Costongs, Caroline; Michelsen, Kai; Brand, Helmut

    2014-03-26

    The concept of capacity building for public health has gained much attention during the last decade. National as well as international organizations increasingly focus their efforts on capacity building to improve performance in the health sector. During the past two decades, a variety of conceptual frameworks have been developed which describe relevant dimensions for public health capacity. Notably, these frameworks differ in design and conceptualization. This paper therefore reviews the existing conceptual frameworks and integrates them into one framework, which contains the most relevant dimensions for public health capacity at the country- or regional level. A comprehensive literature search was performed to identify frameworks addressing public health capacity building at the national or regional level. We content-analysed these frameworks to identify the core dimensions of public health capacity. The dimensions were subsequently synthesized into a set of thematic areas to construct a conceptual framework which describes the most relevant dimensions for capacities at the national- or regional level. The systematic review resulted in the identification of seven core domains for public health capacity: resources, organizational structures, workforce, partnerships, leadership and governance, knowledge development and country specific context. Accordingly, these dimensions were used to construct a framework, which describes these core domains more in detail. Our research shows that although there is no generally agreedupon model of public health capacity, a number of key domains for public health and health promotion capacity are consistently recurring in existing frameworks, regardless of their geographical location or thematic area. As only little work on the core concepts of public health capacities has yet taken place, this study adds value to the discourse by identifying these consistencies across existing frameworks and by synthesising them into a new

  6. Promoting Regionally-Based Climate Change Education through Collaborations with Formal and Informal Education Institutions

    Science.gov (United States)

    Stylinski, C.; Griswold, M.

    2012-12-01

    Improving climate literacy is necessary to effectively respond to climate change impacts. However, climate change education efforts face significant hurdles both in the classroom and in out-of-school settings. These include addressing uncertainity and the complex mix of drivers and impacts that occur over large spatial and temporal scales. These efforts are further hampered by audiences who are disinterested and resisant to discussions of anthropogenic climate change. Bridging formal and informal education experiences focused on climate change offers a potentially powerful strategy to tackle these challenges. In this session, we will describe our NSF-funded Maryland-Delaware Climate Change Education, Assessment and Research (MADE-CLEAR) project, which applies a comprehensive regional partnership among scientists, education researchers, K-12 and informal education practitioners, and other stakeholders to improve public and student understanding of and engagement in climate change issues and solutions. To better understand gaps and opportunities, we have conducted surveys and interviews with K-12, informal, and undergraduate educators and administrators. We found that climate change education aligns with most institutions' missions and efforts, that most educators do not face institutional barriers to climate change education, and that climate change is typically incorporated as part of a host of environmental issues. Despite this, climate change education is still quite limited with few institutions explicitly focusing on climate change in their programming. Additionally, there is little apparent communication among these institutions with regard to this issue. In response to these needs, we have focused the MADE-CLEAR project on creating and providing regionally-relevant resouces and professional development on climate change science, impacts and solutions for both formal and informal educators. Our approach is collaborative and includes strategies to promote

  7. Relationship of interleukin-1B gene promoter region polymorphism with Helicobacter pylori infection and gastritis.

    Science.gov (United States)

    Ramis, Ivy Bastos; Vianna, Júlia Silveira; Halicki, Priscila Cristina Bartolomeu; Lara, Caroline; Tadiotto, Thássia Fernanda; da Silva Maciel, João Batista; Gonçalves, Carla Vitola; von Groll, Andrea; Dellagostin, Odir Antônio; da Silva, Pedro Eduardo Almeida

    2015-09-29

    Helicobacter pylori infection is associated with gastritis, peptic ulcer disease and gastric carcinoma. The severity of damage is determined by the interplay between environmental/behavioral factors, bacterial pathogenicity genes and host genetic polymorphisms that can influence the secretion levels of inflammatory cytokines. Accordingly, this study aimed to identify polymorphisms in the IL-1B and IL-1RN genes and their associations with H. pylori infection, cagA gene of H. pylori, and gastroduodenal diseases. Gastric biopsy samples from 151 patients infected with H. pylori and 76 uninfected individuals were analyzed. H. pylori infection was diagnosed by histology and PCR. Polymorphisms at positions -511, -31 and +3954 of the IL-1B gene were detected by PCR-RFLP, and an analysis of the VNTR polymorphism of the IL-1RN gene was performed by PCR. It was observed that the presence of the T/T genotype at position -511 and the C/C genotype at position -31 were associated with H. pylori infection and with an increased risk of gastritis in H. pylori-positive patients. Additionally, strains from patients H. pylori-positive carrying the cagA gene was significantly related with the T/T genotype at position -511 of IL-1B.  No association of polymorphisms at position +3954 of IL-1B and in the IL-1RN with H. pylori infection and with risk of severe gastric diseases was found. We demonstrated that polymorphisms in the promoter region of the IL-1B gene (at positions -511 and -31) are associated with an enhanced risk of H. pylori infection as well as gastritis in H. pylori-positive patients.

  8. The rs2233678 polymorphism in PIN1 promoter region reduced cancer risk: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Qi Li

    Full Text Available BACKGROUND: Published evidence suggests that the rs2233678 (-842 G>C polymorphism in the PIN1 (peptidyl-prolyl cis/trans somerase NIMA-interacting 1 promoter region may be associated with cancer risk; however, the conclusion is still inconclusive. METHODS: We conducted a meta-analysis to determine whether -842 G>C polymorphism was associated with cancer risk. Odds ratio (OR and 95% confidence intervals (95% CI were used to assess the strength of association. Genotype distribution data and adjusted ORs were collected to calculate the pooled ORs. Meta-regression was conducted to detect the source of heterogeneity. Publication bias was evaluated by Egger's test and Begg's test. RESULTS: A total of 11 eligible studies, including 9280 participants, were identified and analyzed. Overall, we found that carriers of the -842 C allele were associated with significantly decreased cancer risk (C vs. G, OR = 0.750, 95% CI: 0.639-0.880, P(heterogeneity = 0.014, estimated by genotype distribution data; CC+GC vs. GG, OR = 0.668, 95% CI: 0.594-0.751, P(heterogeneity = 0.638, estimated by adjusted ORs. No evidence of publication bias was observed. Meta-regression revealed that ethnicities (p = 0.021 and sample size (p = 0.02 but not sources of control (p = 0.069 were the source of heterogeneity. CONCLUSION: These results suggest that the PIN1 rs2233678 (-842 G>C polymorphism significantly reduces cancer risk.

  9. Comparison of fatty acid and proximate compositions of the body and claw of male and female blue crabs (Callinectes sapidus) from different regions of the Mediterranean coast.

    Science.gov (United States)

    Kuley, Esmeray; Ozoğul, Fatih; Ozogul, Yesim; Olgunoglu, A Ilkan

    2008-01-01

    Fatty acid and proximate compositions of the body and claw of male and female blue crabs from Akyatan Lagoon and Hurma strait were investigated. Male blue crab meat had a higher protein and fat content, and lower moisture and ash content, than that of the female from Akyatan Lagoon. Moreover, there were variations of protein and fat amounts in both female crab meats between Akyatan Lagoon and Hurma strait. The dominant saturated fatty acids were palmitic acid (16:0; range from approximately 12% to 15%) and stearic acid (18:0; range from approximately 7.5% to 16.1%) for all samples. The total monounsaturated fatty acid content in the body of female crabs from Akyatan Lagoon was higher than those of Hurma Strait (22.04% versus 7.55%). There were no statistically significant differences (P>0.05) between eicosapentaenoic acid concentrations in body meat of the male crab than those of female crab meat from Akyatan Lagoon (Pcrabs from Akyatan Lagoon and those of female crabs from Hurma strait. The total n3 was detected as 27.33% in body meat whereas it was 24.39% in claw meat of the male crab from Akyatan Lagoon. Those values were almost similar in the body and claw meat of female crab from Akyatan Lagoon.

  10. Functional characterization of the 5'-flanking and the promoter region of the human UCP3 (hUCP3) gene.

    Science.gov (United States)

    Tu, N; Chen, H; Winnikes, U; Reinert, I; Pirke, K M; Lentes, K U

    2000-09-22

    Uncoupling protein-3 (UCP3) is considered as an important regulator of energy expenditure and thermogenesis in humans. To get insight into the mechanisms regulating its expression we have cloned and characterized about 5 kb of the 5'-flanking region of the human UCP3 (hUCP3) gene. 5'-RACE analysis suggested a single transcription initiation site 187 bp upstream from the translational start site. The promoter region contains both TATA and CAAT boxes as well as consensus motifs for PPRE, TRE, CRE and muscle-specific factors like MyoD and MEF2 sites. Functional characterization of a 3 kb hUCP3 promoter fragment in multiple cell lines using a CAT-ELISA identified a cis-acting negative regulatory element between -2983 and -982 while the region between -982 and -284 showed greatly increased basal promoter activity suggesting the presence of a strong enhancer element. Promoter activity was particularly enhanced in the murine skeletal muscle cell line C2C12 reflecting the tissue-selective expression pattern of UCP3.

  11. Quadruplex forming promoter region of c-myc oncogene as a potential target for a telomerase inhibitory plant alkaloid, chelerythrine.

    Science.gov (United States)

    Ghosh, Saptaparni; Dasgupta, Dipak

    2015-03-27

    Guanine rich sequences present in the promoter region of oncogenes could fold into G-quadruplexes and modulate transcription. Equilibrium between folding and unfolding of the quadruplexes in these regions play important role in disease processes. We have studied the effect of a putative anticancer agent chelerythrine on G-rich NHE III1 present in the promoter region of c-myc oncogene. We have demonstrated the ability of chelerythrine, a telomerase inhibitor, to block the hybridization of Pu27 with its complementary strand via folding it into a quadruplex structure. Calorimetry shows that the association of Pu27 with chelerythrine is primarily enthalpy driven with high binding affinity (∼10(5) M(-1)). The association does not lead to any major structural perturbation of Pu27. The resulting 2:1 complex has enhanced stability as compared to free Pu27. Another notable feature is that the presence of molecular crowding agent like ficoll 70 does not change the mode of recognition though the binding affinity decreases. We suggest that the anticancer activity of chelerythrine could be ascribed to its ability to stabilize the quadruplex structure in the c-myc promoter region thereby downregulating its transcription. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. A prospective evaluation of first people’s health promotion program design in the goulburn-murray rivers region

    Directory of Open Access Journals (Sweden)

    Joyce Doyle

    2016-11-01

    achieve change. Conclusion First Peoples’ health promotion in the Goulburn-Murray Rivers region encompasses a broad range of social, cultural, lifestyle and community development activities, including reclaiming and strengthening cultural identity and social connectedness as a response to colonisation.

  13. A prospective evaluation of first people's health promotion program design in the goulburn-murray rivers region.

    Science.gov (United States)

    Doyle, Joyce; Atkinson-Briggs, Sharon; Atkinson, Petah; Firebrace, Bradley; Calleja, Julie; Reilly, Rachel; Cargo, Margaret; Riley, Therese; Crumpen, Tui; Rowley, Kevin

    2016-11-10

    Aboriginal Community Controlled Organisations (ACCOs) provide community-focussed and culturally safe services for First Peoples in Australia, including crisis intervention and health promotion activities, in a holistic manner. The ecological model of health promotion goes some way towards describing the complexity of such health programs. The aims of this project were to: 1) identify the aims and purpose of existing health promotion programs conducted by an alliance of ACCOs in northern Victoria, Australia; and 2) evaluate the extent to which these programs are consistent with an ecological model of health promotion, addressing both individual and environmental determinants of health. The project arose from a long history of collaborative research. Three ACCOs and a university formed the Health Promotion Alliance to evaluate their health promotion programs. Local community members were trained in, and contributed to developing culturally sensitive methods for, data collection. Information on the aims and design of 88 health promotion activities making up 12 different programs across the ACCOs was systematically and prospectively collected. There was a wide range of activities addressing environmental and social determinants of health, as well as physical activity, nutrition and weight loss. The design of the great majority of activities had a minimal Western influence and were designed within a local Aboriginal cultural framework. The most common focus of the activities was social connectedness (76 %). Physical activity was represented in two thirds of the activities, and nutrition, weight loss and culture were each a focus of about half of the activities. A modified coding procedure designed to assess the ecological nature of these programs showed that they recruited from multiple settings; targeted a range of individual, social and environmental determinants; and used numerous and innovative strategies to achieve change. First Peoples' health promotion in the

  14. Proximity of Radiation Desiccation Response Motif to the core promoter is essential for basal repression as well as gamma radiation-induced gyrB gene expression in Deinococcus radiodurans.

    Science.gov (United States)

    Anaganti, Narasimha; Basu, Bhakti; Mukhopadhyaya, Rita; Apte, Shree Kumar

    2017-06-05

    The radioresistant D. radiodurans regulates its DNA damage regulon (DDR) through interaction between a 17bp palindromic cis-regulatory element called the Radiation Desiccation Response Motif (RDRM), the DdrO repressor and a protease IrrE. The role of RDRM in regulation of DDR was dissected by constructing RDRM sequence-, position- or deletion-variants of Deinococcal gyrB gene (DR0906) promoter and by RDRM insertion in the non-RDRM groESL gene (DR0606) promoter, and monitoring the effect of such modifications on the basal as well as gamma radiation inducible promoter activity by quantifying fluorescence of a GFP reporter. RDRM sequence-variants revealed that the conservation of sequence at the 5th and 13th position and the ends of RDRM is essential for basal repression by interaction with DdrO. RDRM position-variants showed that the sequence acts as a negative regulatory element only when located around transcription start site (TSS) and within the span of RNA polymerase (RNAP) binding region. RDRM deletion-variants indicated that the 5' sequence of RDRM possibly possesses an enhancer-like element responsible for higher expression yields upon repressor clearance post-irradiation. The results suggest that RDRM plays both a negative as well as a positive role in the regulation of DDR in D. radiodurans. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Natural selection in a population of Drosophila melanogaster explained by changes in gene expression caused by sequence variation in core promoter regions.

    Science.gov (United States)

    Sato, Mitsuhiko P; Makino, Takashi; Kawata, Masakado

    2016-02-09

    Understanding the evolutionary forces that influence variation in gene regulatory regions in natural populations is an important challenge for evolutionary biology because natural selection for such variations could promote adaptive phenotypic evolution. Recently, whole-genome sequence analyses have identified regulatory regions subject to natural selection. However, these studies could not identify the relationship between sequence variation in the detected regions and change in gene expression levels. We analyzed sequence variations in core promoter regions, which are critical regions for gene regulation in higher eukaryotes, in a natural population of Drosophila melanogaster, and identified core promoter sequence variations associated with differences in gene expression levels subjected to natural selection. Among the core promoter regions whose sequence variation could change transcription factor binding sites and explain differences in expression levels, three core promoter regions were detected as candidates associated with purifying selection or selective sweep and seven as candidates associated with balancing selection, excluding the possibility of linkage between these regions and core promoter regions. CHKov1, which confers resistance to the sigma virus and related insecticides, was identified as core promoter regions that has been subject to selective sweep, although it could not be denied that selection for variation in core promoter regions was due to linked single nucleotide polymorphisms in the regulatory region outside core promoter regions. Nucleotide changes in core promoter regions of CHKov1 caused the loss of two basal transcription factor binding sites and acquisition of one transcription factor binding site, resulting in decreased gene expression levels. Of nine core promoter regions regions associated with balancing selection, brat, and CG9044 are associated with neuromuscular junction development, and Nmda1 are associated with learning

  16. Methylation of the DCLK1 promoter region in circulating free DNA and its prognostic value in lung cancer patients.

    Science.gov (United States)

    Powrózek, T; Krawczyk, P; Nicoś, M; Kuźnar-Kamińska, B; Batura-Gabryel, H; Milanowski, J

    2016-04-01

    The possibility of detection of suppressor genes methylation in circulating free DNA (cf-DNA) of cancer patients and the lack of methylation in healthy individuals makes this epigenetic alternation an ideal diagnostic marker of neoplastic processes. Moreover, hypermethylation in several genes promoter was described as a biomarker of lung cancer. Methylation in the gene encoding doublecortin-like kinase 1 (DCLK1) is observed in patients with colorectal cancer and cholangiocarcinoma. However, there are no studies concerning DCLK1 methylation in lung cancer patients. The aims of the study was to evaluate the frequency of DCLK1 promoter methylation in cf-DNA of lung cancer patients and of healthy persons as well as the usefulness of this test for predicting the lung cancer course. DCLK1 methylation status was evaluated in DNA isolated from peripheral blood plasma from 65 lung cancer patients and 95 healthy individuals. After DNA bisulfitation, DCLK1 methylation was determined using the qMSP-PCR technique. Moreover, the presence of DCLK1 methylation was correlated with the overall survival (OS) probability of lung cancer patients. DCLK1 promoter methylation was detected in 32 lung cancer patients (49.2 %) and 8 healthy individuals (8.4 %). The methylation of the region before transcription start site (TSS) and the region after TSS of DCLK1 gene was detected in 28 and 11 patients, respectively. In seven cases (10.8 %), the DCLK1 promoter methylation in both regions was reported simultaneously. The methylation was observed slightly frequently in patients with small cell lung cancer (75 % of SCLC patients). The median overall survival of patients with DCLK1 promoter methylation was lower than that of patients without DCLK1 gene modification (p = methylation may be useful in both early diagnosis and prediction of the course of lung cancer.

  17. Allelic polymorphisms in the repeat and promoter regions of the interleukin-4 gene and malaria severity in Ghanaian children

    DEFF Research Database (Denmark)

    Gyan, B A; Goka, B; Cvetkovic, J T

    2004-01-01

    Immunoglobulin E has been associated with severe malaria suggesting a regulatory role for interleukin (IL)-4 and/or IgE in the pathogenesis of severe malaria. We have investigated possible associations between polymorphisms in the IL-4 repeat region (intron 3) and promoter regions (IL-4 +33CT...... groups. Carriers of IL-4 +33T/-590T with cerebral malaria had elevated total IgE compared to non-carriers (P = 0.03). Our data suggest that IL-4 and/or IgE play a regulatory role in the pathogenesis of severe or complicated malaria....

  18. Hepatitis B viral core protein disrupts human host gene expression by binding to promoter regions

    Directory of Open Access Journals (Sweden)

    Guo Yanhai

    2012-10-01

    Full Text Available Abstract Background The core protein (HBc of hepatitis B virus (HBV has been implicated in the malignant transformation of chronically-infected hepatocytes and displays pleiotropic functions, including RNA- and DNA-binding activities. However, the mechanism by which HBc interacts with the human genome to exert effects on hepatocyte function remains unknown. This study investigated the distribution of HBc binding to promoters in the human genome and evaluated its effects on the related genes’ expression. Results Whole-genome chromatin immunoprecipitation microarray (ChIP-on-chip analysis was used to identify HBc-bound human gene promoters. Gene Ontology and pathway analyses were performed on related genes. The quantitative polymerase chain reaction assay was used to verify ChIP-on-chip results. Five novel genes were selected for luciferase reporter assay evaluation to assess the influence of HBc promoter binding. The HBc antibody immunoprecipitated approximately 3100 human gene promoters. Among these, 1993 are associated with known biological processes, and 2208 regulate genes with defined molecular functions. In total, 1286 of the related genes mediate primary metabolic processes, and 1398 encode proteins with binding activity. Sixty-four of the promoters regulate genes related to the mitogen-activated protein kinase (MAPK pathways, and 41 regulate Wnt/beta-catenin pathway genes. The reporter gene assay indicated that HBc binding up-regulates proto-oncogene tyrosine-protein kinase (SRC, type 1 insulin-like growth factor receptor (IGF1R, and neurotrophic tyrosine kinase receptor 2 (NTRK2, and down-regulates v-Ha-ras Harvey rat sarcoma viral oncogene (HRAS. Conclusion HBc has the ability to bind a large number of human gene promoters, and can disrupt normal host gene expression. Manipulation of the transcriptional profile in HBV-infected hepatocytes may represent a key pathogenic mechanism of HBV infection.

  19. Evidence for RNA synthesis in the intergenic region between enhancer and promoter and its inhibition by insulators in Drosophila melanogaster

    Science.gov (United States)

    Tchurikov, Nickolai A.; Kretova, Olga V.; Moiseeva, Evgenia D.; Sosin, Dmitri V.

    2009-01-01

    Uncovering the nature of communication between enhancers, promoters and insulators is important for understanding the fundamental mechanisms that ensure appropriate gene expression levels. Here we describe an approach employing transient expression of genetic luciferase reporter gene constructs with quantitative RT–PCR analysis of transcription between an enhancer and Hsp70 promoter. We tested genetic constructs containing gypsy and/or Fab7 insulators in different orientations, and an enhancer from copia LTR-retroelement [(enh)copia]. A single gypsy or Fab7 insulator inserted between the promoter and enhancer in any polarity reduced enhancer action. A pair of insulators flanking the gene in any orientation exhibited increased insulation activity. We detected promoter-independent synthesis of non-coding RNA in the intergenic region of the constructs, which was induced by the enhancer in both directions and repressed by a single insulator or a pair of insulators. These results highlight the involvement of RNA-tracking mechanisms in the communications between enhancers and promoters, which are inhibited by insulators. PMID:19022852

  20. Stabilization of the promoter nucleosomes in nucleosome-free regions by the yeast Cyc8–Tup1 corepressor

    Science.gov (United States)

    Chen, Kaifu; Wilson, Marenda A.; Hirsch, Calley; Watson, Anjanette; Liang, Shoudan; Lu, Yue; Li, Wei; Dent, Sharon Y.R.

    2013-01-01

    The yeast Cyc8 (also known as Ssn6)–Tup1 complex regulates gene expression through a variety of mechanisms, including positioning of nucleosomes over promoters of some target genes to limit accessibility to the transcription machinery. To further define the functions of Cyc8–Tup1 in gene regulation and chromatin remodeling, we performed genome-wide profiling of changes in nucleosome organization and gene expression that occur upon loss of CYC8 or TUP1 and observed extensive nucleosome alterations in both promoters and gene bodies of derepressed genes. Our improved nucleosome profiling and analysis approaches revealed low-occupancy promoter nucleosomes (P nucleosomes) at locations previously defined as nucleosome-free regions. In the absence of CYC8 or TUP1, this P nucleosome is frequently lost, whereas nucleosomes are gained at −1 and +1 positions, accompanying up-regulation of downstream genes. Our analysis of public ChIP-seq data revealed that Cyc8 and Tup1 preferentially bind TATA-containing promoters, which are also enriched in genes derepressed upon loss of CYC8 or TUP1. These results suggest that stabilization of the P nucleosome on TATA-containing promoters may be a central feature of the repressive chromatin architecture created by the Cyc8–Tup1 corepressor, and that releasing the P nucleosome contributes to gene activation. PMID:23124522

  1. Surveillance, health promotion and control of Chagas disease in the Amazon Region--Medical attention in the Brazilian Amazon Region: a proposal.

    Science.gov (United States)

    Coura, José Rodrigues; Junqueira, Angela C V

    2015-11-01

    We refer to Oswaldo Cruz's reports dating from 1913 about the necessities of a healthcare system for the Brazilian Amazon Region and about the journey of Carlos Chagas to 27 locations in this region and the measures that would need to be adopted. We discuss the risks of endemicity of Chagas disease in the Amazon Region. We recommend that epidemiological surveillance of Chagas disease in the Brazilian Amazon Region and Pan-Amazon region should be implemented through continuous monitoring of the human population that lives in the area, their housing, the environment and the presence of triatomines. The monitoring should be performed with periodic seroepidemiological surveys, semi-annual visits to homes by health agents and the training of malaria microscopists and healthcare technicians to identify Trypanosoma cruzi from patients' samples and T. cruzi infection rates among the triatomines caught. We recommend health promotion and control of Chagas disease through public health policies, especially through sanitary education regarding the risk factors for Chagas disease. Finally, we propose a healthcare system through base hospitals, intermediate-level units in the areas of the Brazilian Amazon Region and air transportation, considering the distances to be covered for medical care.

  2. Advantages and disadvantages in usage of bioinformatic programs in promoter region analysis

    Science.gov (United States)

    Pawełkowicz, Magdalena E.; Skarzyńska, Agnieszka; Posyniak, Kacper; ZiÄ bska, Karolina; PlÄ der, Wojciech; Przybecki, Zbigniew

    2015-09-01

    An important computational challenge is finding the regulatory elements across the promotor region. In this work we present the advantages and disadvantages from the application of different bioinformatics programs for localization of transcription factor binding sites in the upstream region of genes connected with sex determination in cucumber. We use PlantCARE, PlantPAN and SignalScan to find motifs in the promotor regions. The results have been compared and possible function of chosen motifs has been described.

  3. Vitamin D responsive elements within the HLA-DRB1 promoter region in Sardinian multiple sclerosis associated alleles.

    Directory of Open Access Journals (Sweden)

    Eleonora Cocco

    Full Text Available Vitamin D response elements (VDREs have been found in the promoter region of the MS-associated allele HLA-DRB1*15:01, suggesting that with low vitamin D availability VDREs are incapable of inducing *15:01 expression allowing in early life autoreactive T-cells to escape central thymic deletion. The Italian island of Sardinia exhibits a very high frequency of MS and high solar radiation exposure. We test the contribution of VDREs analysing the promoter region of the MS-associated DRB1 *04:05, *03:01, *13:01 and *15:01 and non-MS-associated *16:01, *01, *11, *07:01 alleles in a cohort of Sardinians (44 MS patients and 112 healthy subjects. Sequencing of the DRB1 promoter region revealed a homozygous canonical VDRE in all *15:01, *16:01, *11 and in 45/73 *03:01 and in heterozygous state in 28/73 *03:01 and all *01 alleles. A new mutated homozygous VDRE was found in all *13:03, *04:05 and *07:01 alleles. Functionality of mutated and canonical VDREs was assessed for its potential to modulate levels of DRB1 gene expression using an in vitro transactivation assay after stimulation with active vitamin D metabolite. Vitamin D failed to increase promoter activity of the *04:05 and *03:01 alleles carrying the new mutated VDRE, while the *16:01 and *03:01 alleles carrying the canonical VDRE sequence showed significantly increased transcriptional activity. The ability of VDR to bind the mutant VDRE in the DRB1 promoter was evaluated by EMSA. Efficient binding of VDR to the VDRE sequence found in the *16:01 and in the *15:01 allele reduced electrophoretic mobility when either an anti-VDR or an anti-RXR monoclonal antibody was added. Conversely, the Sardinian mutated VDRE sample showed very low affinity for the RXR/VDR heterodimer. These data seem to exclude a role of VDREs in the promoter region of the DRB1 gene in susceptibility to MS carried by DRB1* alleles in Sardinian patients.

  4. Association of polymorphisms of interleukin-18 gene promoter region with polycystic ovary syndrome in chinese population

    Directory of Open Access Journals (Sweden)

    Li Mei-zhi

    2010-10-01

    Full Text Available Abstract Background Recent research shows that polycystic ovary syndrome (PCOS may have an association with low-grade chronic inflammation, and that PCOS may induce an increase in serum interleukin-18 (IL-18 levels. Methods To investigate the polymorphisms of the IL-18 gene promoters with PCOS, two single nucleotide polymorphisms (SNPs in the promoter of the IL-18 gene (at positions -607C/A and -137G/C in 118 Chinese women with PCOS and 79 controls were evaluated using polymerase chain reaction (PCR. Results No significant differences were found in the genotype distribution, allele frequency and haplotype frequency between the PCOS and control groups. Further analysis demonstrated a relationship between IL-18 gene promoter polymorphisms and PCOS insulin resistance (IR. Regarding the -137 allele frequency, G and C allele frequencies were 93.5% and 6.5%, respectively, in the PCOS with IR patients; G and C allele frequencies were 85.4% and 14.6%, respectively, in PCOS patients without IR (chi2 = 3.601, P = 0.048. Conclusions The presence of a polymorphism in the IL-18 gene was found to have no correlation with the occurrence of PCOS. Carriage of the C allele at position -137 in the promoter of the IL-18 gene may play a protective role from the development of PCOS IR.

  5. Evaluation of methylation pattern in promoter region of E-cadherin ...

    African Journals Online (AJOL)

    The data indicate that CDH1 promoter methylation might be a potential mechanism for epigenetic silencing of CDH1 in primary breast cancer suggesting a valuable molecular marker for detection of breast cancer progression. Key words: Breast cancer, E-cadherin, methylation pattern, tumor stage, tumor grade.

  6. Promoter activity associated with the intergenic regions of banana bunchy top virus DNA-1 to -6 in transgenic tobacco and banana cells.

    Science.gov (United States)

    Dugdale, B; Beetham, P R; Becker, D K; Harding, R M; Dale, J L

    1998-10-01

    Promoter regions associated with each of the six ssDNA components of banana bunchy top virus (BBTV) have been characterized. DNA segments incorporating the intergenic regions of BBTV DNA-1 to -6 were isolated and fused to the uidA (beta-glucuronidase) reporter gene to assess promoter activity. In tobacco cell suspensions, the BBTV DNA-2 and -6 promoters generated levels of GUS expression 2-fold greater and similar to the 800 bp CaMV 35S promoter, respectively. Deletion analysis of the BBTV DNA-6 promoter suggested all the necessary promoter elements required for strong expression were located within 239 nucleotides upstream of the translational start codon. In transgenic tobacco plants, the BBTV-derived promoters generally provided a weak, tissue-specific GUS expression pattern restricted to phloem-associated cells. However, in callus derived from tobacco leaf tissue, GUS expression directed by the BBTV DNA-6 promoter was strong and, in some lines, comparable to the CaMV 35S promoter. Detectable promoter activity associated with the BBTV promoters in banana embryogenic cells was only observed using a sensitive green fluorescent protein (GFP) reporter. Promoters derived from BBTV DNA-4 and -5 generated the highest levels of transient activity, which were greater than that of the maize ubi-1 promoter. In transgenic banana plants, the activity of the BBTV DNA-6 promoter was restricted to the phloem of leaves and roots, stomata and root meristems.

  7. Promoting survival: A grounded theory study of consequences of modern health practices in Ouramanat region of Iranian Kurdistan

    Science.gov (United States)

    Mohammadpur, Ahmad; Rezaei, Mehdi; Sadeghi, Rasoul

    2010-01-01

    The aim of this qualitative study is to explore the way people using modern health care perceive its consequences in Ouraman-e-Takht region of Iranian Kurdistan. Ouraman-e-Takht is a rural, highly mountainous and dry region located in the southwest Kurdistan province of Iran. Recently, modern health practices have been introduced to the region. The purpose of this study was to investigate, from the Ouramains' point of view, the impact that modern health services and practices have had on the Ouraman traditional way of life. Interview data from respondents were analyzed by using grounded theory. Promoting survival was the core category that explained the impact that modern health practices have had on the Ouraman region. The people of Ouraman interpreted modern health practices as increasing their quality of life and promoting their survival. Results are organized around this core category in a paradigm model consisting of conditions, interactions, and consequences. This model can be used to understand the impact of change from the introduction of modern health on a traditional society. PMID:20640020

  8. Analysis of the Impact of the Flow of Migrant Workers on Regional Economy: Based on the Thought about the Promotion of Jiangxi Regional Economic Competitiveness

    Directory of Open Access Journals (Sweden)

    Sun Yuping

    2016-03-01

    Full Text Available Labor resource is the necessary productive factor in regional economic development, and one of important indexes to evaluate regional economic competitiveness. The great economic achievement brought by the 30-year reform and opening up of China is due to the fact that China brought the backward advantage of “demographic dividend” into play, promoted the fast development of industrialization and urbanization, and became the second largest economy in the world. The entity of “demographic dividend” is the non-agricultural migrant population, i.e., migrant workers. The transfer employment of migrant workers has typical regional liquidity, and the imbalance of regional economy causes the flow of many migrant workers. In order to achieve harmonious development and coordinated development, underdeveloped areas must understand the character and regulation, adopt positive industrial policy and supportive policy, guide the reasonable flow of migrant workers, and realize the transfer of local employment and citizenization of migrant workers, which can enhance regional economic competitiveness

  9. Promotion of physical activity in the European region: content analysis of 27 national policy documents

    DEFF Research Database (Denmark)

    Daugbjerg, Signe B; Kahlmeier, Sonja; Racioppi, Francesca

    2009-01-01

    BACKGROUND: Over the past years there has been increasing interest in physical activity promotion and the development of appropriate policy. So far, there has been no comprehensive overview of the activities taking place in Europe in this area of public health policy. METHODS: Using different....... Population groups most in need such as people with low levels of physical activity were rarely specifically targeted. Most policies emphasized the importance of an evaluation. However, only about half of them indicated a related intention or requirement. CONCLUSION: In recent years there has been...... search methods, 49 national policy documents on physical activity promotion were identified. An analysis grid covering key features was developed for the analysis of the 27 documents published in English. RESULTS: Analysis showed that many general recommendations for policy developments are being...

  10. Single-nucleotide polymorphisms in the promoter region of the PARKIN gene and Parkinson's disease.

    Science.gov (United States)

    Mata, Ignacio F; Alvarez, Victoria; García-Moreira, Vanessa; Guisasola, Luis M; Ribacoba, René; Salvador, Carlos; Blázquez, Marta; Sarmiento, Rogelio González; Lahoz, Carlos H; Menes, Bernardino B; García, Eliecer Coto

    2002-08-30

    Mutations in the PARKIN gene have been identified in families with recessively inherited Parkinson disease (PD). Common DNA-polymorphisms at the PARKIN gene could contribute to the risk for PD in the general population. Here we searched for DNA-polymorphisms in the PARKIN promoter. We found two single nucleotide polymorphisms (-324 A/G and -797 A/G). In order to analyse the association of PD with these and two previously described polymorphisms (1281 G/A, Asp394Asn, and 601 G/A, Ser167Asn) we genotyped 105 patients and 150 healthy controls. Allele and genotype frequencies for the four polymorphisms did not differ between patients and controls, or between patients with an early-onset (40 years; n = 85). According to our data, the genetic variation at the PARKIN gene (including promoter polymorphisms) did not contribute to the risk of developing PD in the general population. Copyright 2002 Elsevier Science Ireland Ltd.

  11. DNMT 1 maintains hypermethylation of CAG promoter specific region and prevents expression of exogenous gene in fat-1 transgenic sheep.

    Science.gov (United States)

    Yang, Chunrong; Shang, Xueying; Cheng, Lei; Yang, Lei; Liu, Xuefei; Bai, Chunling; Wei, Zhuying; Hua, Jinlian; Li, Guangpeng

    2017-01-01

    Methylation is an important issue in gene expression regulation and also in the fields of genetics and reproduction. In this study, we created fat-1 transgenic sheep, investigated the fine-mapping and the modulatory mechanisms of promoter methylation. Sheep fetal fibroblasts were transfected by pCAG-fat1-IRES-EGFP. Monoclonal cell line was screened as nuclear donor and carried out nuclear transfer (441 transgenic cloned embryos, 52 synchronism recipient sheep). Six offsprings were obtained. Expressions of exogenous genes fat-1 and EGFP were detectable in 10 examined tissues and upregulated omega-3 fatty acid content. Interestingly, more or less EGFP negative cells were detectable in the positive transgenic fetal skin cells. EGFP negative and positive cells were sorted by flow cytometry, and their methylation status in the whole promoter region (1701 nt) were investigated by bisulphate sequencing. The fine-mapping of methylation in CAG promoter were proposed. The results suggested that exogenous gene expression was determined by the methylation status from 721-1346 nt and modulated by methylation levels at 101, 108 and 115 nt sites in CAG promoter. To clarify the regulatory mechanism of methylation, examination of four DNA methyltransferases (DNMTs) demonstrated that hypermethylation of CAG promoter is mainly maintained by DNMT 1 in EGFP negative cells. Furthermore, investigation of the cell surface antigen CD34, CD45 and CD166 indicated that EGFP positive and negative cells belong to different types. The present study systematically clarified methylation status of CAG promoter in transgenic sheep and regulatory mechanism, which will provide research strategies for gene expression regulation in transgenic animals.

  12. Finding Combination of Features from Promoter Regions for Ovarian Cancer-related Gene Group Classification

    KAUST Repository

    Olayan, Rawan S.

    2012-12-01

    In classification problems, it is always important to use the suitable combination of features that will be employed by classifiers. Generating the right combination of features usually results in good classifiers. In the situation when the problem is not well understood, data items are usually described by many features in the hope that some of these may be the relevant or most relevant ones. In this study, we focus on one such problem related to genes implicated in ovarian cancer (OC). We try to recognize two important OC-related gene groups: oncogenes, which support the development and progression of OC, and oncosuppressors, which oppose such tendencies. For this, we use the properties of promoters of these genes. We identified potential “regulatory features” that characterize OC-related oncogenes and oncosuppressors promoters. In our study, we used 211 oncogenes and 39 oncosuppressors. For these, we identified 538 characteristic sequence motifs from their promoters. Promoters are annotated by these motifs and derived feature vectors used to develop classification models. We made a comparison of a number of classification models in their ability to distinguish oncogenes from oncosuppressors. Based on 10-fold cross-validation, the resultant model was able to separate the two classes with sensitivity of 96% and specificity of 100% with the complete set of features. Moreover, we developed another recognition model where we attempted to distinguish oncogenes and oncosuppressors as one group from other OC-related genes. That model achieved accuracy of 82%. We believe that the results of this study will help in discovering other OC-related oncogenes and oncosuppressors not identified as yet.

  13. Association of a Human FABP1 Gene Promoter Region Polymorphism with Altered Serum Triglyceride Levels.

    Directory of Open Access Journals (Sweden)

    Xian-E Peng

    Full Text Available Liver fatty acid-binding protein (L-FABP, also known as fatty acid-binding protein 1 (FABP1, is a key regulator of hepatic lipid metabolism. Elevated FABP1 levels are associated with an increased risk of cardiovascular disease (CVD and metabolic syndromes. In this study, we examine the association of FABP1 gene promoter variants with serum FABP1 and lipid levels in a Chinese population. Four promoter single-nucleotide polymorphisms (SNPs of FABP1 gene were genotyped in a cross-sectional survey of healthy volunteers (n = 1,182 from Fuzhou city of China. Results showed that only the rs2919872 G>A variant was significantly associated with serum TG concentration(P = 0.032.Compared with the rs2919872 G allele, rs2919872 A allele contributed significantly to reduced serum TG concentration, and this allele dramatically decreased the FABP1 promoter activity(P < 0.05. The rs2919872 A allele carriers had considerably lower serum FABP1 levels than G allele carriers (P < 0.01. In the multivariable linear regression analysis, the rs2919872 A allele was negatively associated with serum FABP1 levels (β = -0.320, P = 0.003, while serum TG levels were positively associated with serum FABP1 levels (β = 0.487, P = 0.014. Our data suggest that compared with the rs2919872 G allele, the rs2919872 A allele reduces the transcriptional activity of FABP1 promoter, and thereby may link FABP1 gene variation to TG level in humans.

  14. Association of the Resistin Gene Promoter Region Polymorphism with Kawasaki Disease in Chinese Children

    Directory of Open Access Journals (Sweden)

    Ruixi Liu

    2012-01-01

    Full Text Available Objectives. The −420C>G polymorphism located in the resistin gene (RETN promoter has recently been suggested to play a potential role in proinflammatory conditions and cardiovascular disease. This study investigated the association of the RETN promoter polymorphism with Kawasaki disease (KD and its clinical parameters in Chinese children. Methods. We compared patients with complete KD to incomplete KD children. Genotyping of the RETN promoter polymorphism was performed using MassARRAY system, and serum resistin levels were estimated using the sandwich enzyme immunoassay method. Results. There was no significant difference in RETN (−420C>G genotypes between KD and control groups. However, the frequency of the G allele was higher in iKD patients than in cKD children due to a significantly increased frequency of the GG genotypes. Serum levels of resistin were significantly higher in KD patients than in controls regardless of the presence of coronary artery lesions (CALs. Conclusion. The present findings suggest that while resistin may play a role in the pathogenesis of KD, there is no apparent association between CAL and the RETN (−420C>G gene polymorphism in KD children. However, the diagnosis of iKD is challenging but can be supported by the presence of the G allele and the GG genotypes.

  15. No evidence for promoter region methylation of the succinate dehydrogenase and fumarate hydratase tumour suppressor genes in breast cancer

    Directory of Open Access Journals (Sweden)

    Dobrovic Alexander

    2009-09-01

    Full Text Available Abstract Background Succinate dehydrogenase (SDH and fumarate hydratase (FH are tricarboxylic acid (TCA cycle enzymes that are also known to act as tumour suppressor genes. Increased succinate or fumarate levels as a consequence of SDH and FH deficiency inhibit hypoxia inducible factor-1α (HIF-1α prolyl hydroxylases leading to sustained HIF-1α expression in tumours. Since HIF-1α is frequently expressed in breast carcinomas, DNA methylation at the promoter regions of the SDHA, SDHB, SDHC and SDHD and FH genes was evaluated as a possible mechanism in silencing of SDH and FH expression in breast carcinomas. Findings No DNA methylation was identified in the promoter regions of the SDHA, SDHB, SDHC, SDHD and FH genes in 72 breast carcinomas and 10 breast cancer cell lines using methylation-sensitive high resolution melting which detects both homogeneous and heterogeneous methylation. Conclusion These results show that inactivation via DNA methylation of the promoter CpG islands of SDH and FH is unlikely to play a major role in sporadic breast carcinomas.

  16. Capacitive proximity sensor

    Science.gov (United States)

    Kronberg, James W.

    1994-01-01

    A proximity sensor based on a closed field circuit. The circuit comprises a ring oscillator using a symmetrical array of plates that creates an oscillating displacement current. The displacement current varies as a function of the proximity of objects to the plate array. Preferably the plates are in the form of a group of three pair of symmetric plates having a common center, arranged in a hexagonal pattern with opposing plates linked as a pair. The sensor produces logic level pulses suitable for interfacing with a computer or process controller. The proximity sensor can be incorporated into a load cell, a differential pressure gauge, or a device for measuring the consistency of a characteristic of a material where a variation in the consistency causes the dielectric constant of the material to change.

  17. Neighborhoods and manageable proximity

    Directory of Open Access Journals (Sweden)

    Stavros Stavrides

    2011-08-01

    Full Text Available The theatricality of urban encounters is above all a theatricality of distances which allow for the encounter. The absolute “strangeness” of the crowd (Simmel 1997: 74 expressed, in its purest form, in the absolute proximity of a crowded subway train, does not generally allow for any movements of approach, but only for nervous hostile reactions and submissive hypnotic gestures. Neither forced intersections in the course of pedestrians or vehicles, nor the instantaneous crossing of distances by the technology of live broadcasting and remote control give birth to places of encounter. In the forced proximity of the metropolitan crowd which haunted the city of the 19th and 20th century, as well as in the forced proximity of the tele-presence which haunts the dystopic prospect of the future “omnipolis” (Virilio 1997: 74, the necessary distance, which is the stage of an encounter between different instances of otherness, is dissipated.

  18. Identification of Rhopalosiphum Padi Virus 5′ Untranslated Region Sequences Required for Cryptic Promoter Activity and Internal Ribosome Entry

    Directory of Open Access Journals (Sweden)

    Ming-Kun Liu

    2015-07-01

    Full Text Available The 579-nucleotide 5′ untranslated region (5′UTR of the Rhopalosiphum padi virus (RhPV possesses a cross-kingdom internal ribosome entry site (IRES activity that functions in insect, mammalian, and plant-derived in vitro translation systems, and six TAAG motifs within the DNA fragment encoding the RhPV 5′UTR were previously found to confer the RhPV 5′UTR with late promoter activity in baculovirus. In the present study, various truncated RhPV 5′UTR sequences were produced, and among them, a fragment of 110 bp ranging from nucleotides 309 to 418 was identified to be the shortest fragment responsible for the late promoter activity in baculovirus infected Sf21 cells. This 110 bp fragment contains a TAAG tandem repeat that retains more than 60% of the late promoter activity of the full length RhPV 5′UTR sequence. Further, IRES activity remained unchanged in all truncated RhPV 5′UTR constructs. Taken together, this novel 110 bp fragment having late promoter activity in baculovirus as well as IRES activity in mammalian cell, renders it a useful tool for the development of a “shuttle” bi-cistronic baculovirus gene expression and/or delivery vector.

  19. Identification of Rhopalosiphum Padi Virus 5′ Untranslated Region Sequences Required for Cryptic Promoter Activity and Internal Ribosome Entry

    Science.gov (United States)

    Liu, Ming-Kun; Lin, Jie-Zue; Jinn, Tzyy-Rong; Chan, Hong-Lin; Wu, Tzong-Yuan

    2015-01-01

    The 579-nucleotide 5′ untranslated region (5′UTR) of the Rhopalosiphum padi virus (RhPV) possesses a cross-kingdom internal ribosome entry site (IRES) activity that functions in insect, mammalian, and plant-derived in vitro translation systems, and six TAAG motifs within the DNA fragment encoding the RhPV 5′UTR were previously found to confer the RhPV 5′UTR with late promoter activity in baculovirus. In the present study, various truncated RhPV 5′UTR sequences were produced, and among them, a fragment of 110 bp ranging from nucleotides 309 to 418 was identified to be the shortest fragment responsible for the late promoter activity in baculovirus infected Sf21 cells. This 110 bp fragment contains a TAAG tandem repeat that retains more than 60% of the late promoter activity of the full length RhPV 5′UTR sequence. Further, IRES activity remained unchanged in all truncated RhPV 5′UTR constructs. Taken together, this novel 110 bp fragment having late promoter activity in baculovirus as well as IRES activity in mammalian cell, renders it a useful tool for the development of a “shuttle” bi-cistronic baculovirus gene expression and/or delivery vector. PMID:26184188

  20. Identification of Rhopalosiphum Padi Virus 5' Untranslated Region Sequences Required for Cryptic Promoter Activity and Internal Ribosome Entry.

    Science.gov (United States)

    Liu, Ming-Kun; Lin, Jie-Zue; Jinn, Tzyy-Rong; Chan, Hong-Lin; Wu, Tzong-Yuan

    2015-07-15

    The 579-nucleotide 5' untranslated region (5'UTR) of the Rhopalosiphum padi virus (RhPV) possesses a cross-kingdom internal ribosome entry site (IRES) activity that functions in insect, mammalian, and plant-derived in vitro translation systems, and six TAAG motifs within the DNA fragment encoding the RhPV 5'UTR were previously found to confer the RhPV 5'UTR with late promoter activity in baculovirus. In the present study, various truncated RhPV 5'UTR sequences were produced, and among them, a fragment of 110 bp ranging from nucleotides 309 to 418 was identified to be the shortest fragment responsible for the late promoter activity in baculovirus infected Sf21 cells. This 110 bp fragment contains a TAAG tandem repeat that retains more than 60% of the late promoter activity of the full length RhPV 5'UTR sequence. Further, IRES activity remained unchanged in all truncated RhPV 5'UTR constructs. Taken together, this novel 110 bp fragment having late promoter activity in baculovirus as well as IRES activity in mammalian cell, renders it a useful tool for the development of a "shuttle" bi-cistronic baculovirus gene expression and/or delivery vector.

  1. Atrofia muscular proximal familiar

    Directory of Open Access Journals (Sweden)

    José Antonio Levy

    1962-09-01

    Full Text Available Os autores relatam dois casos de atrofia muscular proximal familiar, moléstia caracterizada por déficit motor e atrofias musculares de distribuição proximal, secundárias a lesão de neurônios periféricos. Assim, como em outros casos descritos na literatura, foi feito inicialmente o diagnóstico de distrofia muscular progressiva. O diagnóstico correto foi conseguido com auxílio da eletromiografia e da biopsia muscular.

  2. Identification of anthranilate and benzoate metabolic operons of Pseudomonas fluorescens and functional characterization of their promoter regions

    Directory of Open Access Journals (Sweden)

    Lee Vincent D

    2006-01-01

    Full Text Available Abstract Background In an effort to identify alternate recombinant gene expression systems in Pseudomonas fluorescens, we identified genes encoding two native metabolic pathways that were inducible with inexpensive compounds: the anthranilate operon (antABC and the benzoate operon (benABCD. Results The antABC and benABCD operons were identified by homology to the Acinetobacter sp. anthranilate operon and Pseudomonas putida benzoate operon, and were confirmed to be regulated by anthranilate or benzoate, respectively. Fusions of the putative promoter regions to the E. coli lacZ gene were constructed to confirm inducible gene expression. Each operon was found to be controlled by an AraC family transcriptional activator, located immediately upstream of the first structural gene in each respective operon (antR or benR. Conclusion We have found the anthranilate and benzoate promoters to be useful for tightly controlling recombinant gene expression at both small (

  3. Perceptions of health promoters about health promotion programmes for families with adolescents orphaned as a result of AIDS in the rural Hammanskraal region in South Africa

    Directory of Open Access Journals (Sweden)

    Maseapo P. Mthobeni

    2013-02-01

    Full Text Available South African communities are still greatly affected by the high rate of infection with HIV or who are living with AIDS, mirrored in the 2008 overall national HIV prevalence of 29.3%(UNAIDS 2010:10. In addressing the challenge, the health system is dependent on community care level workers such as caregivers to render health promotion and education in the homes and communities. The caregivers based in the communities are the ones with first-hand information on what is needed for the success of health promotion programmes. This study, aimed at exploring the challenges faced by the health promoters, described their perceptions regarding a health promotion programme for families with adolescents orphaned as a result of AIDS. Data were collected on the purposively selected participants at the rural Hammanskraal region in South Africa and the research question: ‘What is your perception regarding health promotion programmes for families with adolescents orphaned as a result of AIDS’ was asked and discussed by participants in a focus group interview. Data were analysed using the adapted Tesch method to organize and isolate the main categories, sub-categories and themes. The following main categories were isolated: attitudes of adolescents, effectiveness of home visits, need for health education and limited resources. Based on the findings, it was therefore recommended that health care planners assist in the improvement of health promotion and education by using the community and national media, providing information material and providing access to the internet in order to allow more people, including young people, to access the information.Suid-Afrikaanse gemeenskappe word steeds grootliks beïnvloed deur die hoë vlak van MIV en vigs, soos weerspieël in die algehele nasionale MIV-syfer in 2008 van 29.3% (UNAIDS 2010:10. In die aanspreek van hierdie uitdaging is die gesondheidstelsel afhanklik van gemeenskapsorgwerkers om gesondheidsbevordering

  4. Localization of a gene for autosomal dominant Larsen syndrome to chromosome region 3p21.1-14.1 in the proximity of, but distinct from the COL7A1 locus

    Energy Technology Data Exchange (ETDEWEB)

    Vujic, M.; Hallstensson, K.; Wahlstroem, J. [East Hospital, Gothenburg (Sweden)] [and others

    1995-11-01

    Larsen syndrome (LS) is a skeletal dysplasia (osteochondrodysplasia) in which multiple dislocations of the large joints are the major feature. Nosology in this group of diseases, which constitutes 8% of Mendelian disorders in man, is primarily based on clinical and radiographic features. Hopes for more accurate classification grounds are currently being met by progress in elucidation of underlying genetic defects. We have performed linkage analysis in a large Swedish kindred with autosomal dominant LS and found the gene (LAR1) to be strongly linked to chromosome 3p markers (Z{sub max} = 13.4 at {theta} = .00). Recombination analysis indicates that the LAR1 locus is located in a region defined distally by D3S1581 and proximally by D3S1600, which cytogenetically maps to chromosome region 3p21.1-14.1. Linkage and recombination analysis of a COL7A1 PvuII intragenic polymorphism versus LS and chromosome 3 markers indicate that COL7A1 is located close to, but distinct from, the LAR1 locus. 33 refs., 6 figs., 3 tabs.

  5. A Novel Mutation in the Promoter Region of the β-Globin Gene: HBB: c.-127G > C.

    Science.gov (United States)

    Bilgen, Turker; Canatan, Duran; Delibas, Serpil; Keser, Ibrahim

    2016-08-01

    Novel β-globin gene mutations are still occasionally being reported, especially when evaluating milder phenotypes. We report here a novel putative mutation in the promoter region of the β-globin gene and assess its clinical implications. A family, parents and four siblings, with hematological and clinical features suspected of being β-globin gene mutation(s), were involved in this study. In addition to hematological and clinical evaluations of the whole family, molecular analyses of the β-globin gene were performed by direct sequencing. Sequencing of the β-globin gene revealed a novel genomic alteration in the regulatory region of the gene. This novel genomic alteration was defined as HBB: c.-127G > C according to the Human Genome Variation Society (HGVS) nomenclature. Two siblings were found to be carriers of the HBB: c.-127G > C mutation, while the other two siblings were carriers of the codon 8 (-AA) (HBB: c.25_26delAA) deletion of the β-globin gene. The mother was a compound heterozygote for the codon 8 and HBB: c.-127G > C mutations. Based on hematological and clinical evaluations, we conclude that this novel β-globin gene promoter region change would be associated with a mild phenotype of β-thalassemia (β-thal).

  6. Fish farming as an innovative strategy for promoting food security in drought risk regions of Zimbabwe

    Directory of Open Access Journals (Sweden)

    Elvin Shava

    2017-01-01

    Full Text Available This article examines the implementation of fish farming as an innovative and economic strategy for promoting food security and dietary diversities among vulnerable households in drought risk areas of Zimbabwe. The declining climatic conditions and lack of economic opportunities in Mwenezi district of Zimbabwe attracted the attention of three nongovernmental organisations (NGOs to implement fish farming as an innovative mechanism to stimulate food security and generate employment in the district. The article used a qualitative research approach that includes semi-structured interviews and secondary data. The purposive sampling technique was adopted to interview participants in Mwenezi district who were involved in fish farming to assess and explore the experiences and benefits they derive from such development projects. Results for the article revealed that fish farming was well embraced by local communities as it led to improvements in food security, household income and employment regeneration. The local government including traditional leadership (Chiefs and Headmen’s supported the NGO activities as they benefited local communities. The article concludes that although fish farming was instrumental in regenerating employment, some participants still fail to participate because of laziness and desire to maintain dependency syndrome. The article recommends the NGOs to launch awareness campaigns in rural communities and increase networking with the donor community which is fundamental in attracting sustainable funding. The government can also promote fish farming in vulnerable rural communities by providing funding and capacity building programmes.

  7. Polymorphism in the oxytocin promoter region in patients with lactase non-persistence is not related to symptoms

    Directory of Open Access Journals (Sweden)

    Simrén Magnus

    2009-11-01

    Full Text Available Abstract Background Oxytocin and the oxytocin receptor have been demonstrated in the gastrointestinal (GI tract and have been shown to exert physiological effects on gut motility. The role for oxytocin in the pathophysiology of GI complaints is unknown. The aim of this study was to examine genetic variations or polymorphism of oxytocin (OXT and its receptor (OXTR genes in patients with GI complaints without visible organic abnormalities. Methods Genetic variants in the OXT promoter region, and in the OXTR gene in DNA samples from 131 rigorously evaluated patients with Irritable Bowel Syndrome (IBS, 408 homozygous subjects referred for lactase (LCT-13910 C>T, rs4988235 genotyping, and 299 asymptomatic blood donors were compared. One polymorphism related to the OXT gene (rs6133010 A>G and 4 related to the OXTR gene (rs1465386 G>T, rs3806675 G>A, rs968389 A>G, rs1042778 G>T were selected for genotyping using Applied Biosystems 7900 HT allele discrimination assays. Results There were no statistically significant differences in the genotype or allele frequencies in any of the SNPs when IBS patients were compared to healthy controls. Among subjects referred for lactase genotyping, the rs6133010 A>G OXT promoter A/G genotype tended to be more common in the 154 non-persistent (27.3% subjects than in the 254 lactase persistant (18.1% subjects and in the healthy controls (19.4% (p = 0.08. When direct comparing, the A/G genotype was less common in the OXT promoter region in controls (p = 0.09 and in subjects with lactase persistence (p = 0.03 compared to subjects with lactase non-persistence. When healthy controls were viewed according to their own LCT-13910 genotypes, the C/C lactase non-persistent controls had a higher frequency for the OXT promoter A/G genotype than LCT-13910 T/T lactase persistent controls (41.2% vs 13.1%. No significant differences in frequencies of the investigated OXTR SNPs were noted in this study. Conclusion The results suggest

  8. Human DNA repair genes possess potential G-quadruplex sequences in their promoters and 5`-untranslated regions.

    Science.gov (United States)

    Fleming, Aaron M; Zhu, Judy; Ding, Yun; Visser, Joshua A; Zhu, Julia; Burrows, Cynthia J

    2018-01-10

    The cellular response to oxidative stress includes transcriptional changes, particularly for genes involved in DNA repair. Recently, our laboratory demonstrated that oxidation of 2`-deoxyguanosine (G) to 8-oxo-7,8-dihydro-2`-deoxyguanosine (OG) in G-rich potential G-quadruplex sequences (PQSs) in gene promoters impacts the level of gene expression up or down depending on the position of the PQS in the promoter. In the present report, bioinformatic analysis found that the 390 human DNA repair genes in the genome ontology initiative harbor 2,936 PQSs in their promoters and 5`-untranslated regions (5`-UTRs). The average density of PQSs in human DNA repair genes was found to be nearly twofold greater than the average density of PQSs in all coding and non-coding human genes (7.5 vs. 4.3 per gene). The distribution of the PQSs in the DNA repair genes on the non-transcribed (coding) vs. transcribed strands reflects that of PQSs in all human genes. Next, literature data were interrogated to select 30 PQSs to catalog their ability to adopt G-quadruplex (G4) folds in vitro using five different experimental tests. The G4 characterization experiments concluded that 26 of the 30 sequences could adopt G4 topologies in solution. Last, four PQSs were synthesized into the promoter of a luciferase plasmid and co-transfected with the G4-specific ligands pyridostatin, Phen-DC3, or BRACO-19 in human cells to determine whether the PQSs could adopt G4 folds. The cell studies identified changes in luciferase expression when the G4 ligands were present, and the magnitude of the expression changes dependent on the PQS and the coding vs. template strand on which the sequence resided. Our studies demonstrate PQSs exist at a high density in human DNA repair gene promoters and a subset of the identified sequences fold in vitro and in vivo.

  9. Long noncoding RNA PCA3 gene promoter region is related to the risk of prostate cancer on Chinese males.

    Science.gov (United States)

    Zhou, Wu; Tao, Zhihua; Wang, Zhongyong; Hu, Wangqiang; Shen, Mo; Zhou, Lianlian; Wen, Zhiliang; Yu, Zhixian; Wu, Xiuling; Huang, Kate; Hu, Yuanping; Lin, Xiangyang

    2014-12-01

    Long noncoding RNA prostate cancer gene antigen 3 (PCA3) is one of the most prostate cancer-specific genes at present. Consequently, the prostate-specific expression and the sharp up-regulation of PCA3 RNA in prostate cancer suggest a unique transcriptional regulation, which possibly can be attributed to promoter polymorphism. In this study, we investigated a short tandem repeat (STR) polymorphism of TAAA in the promoter region of PCA3 gene found in our previous study in prostate cancer (PCa) patients and benign prostatic hypertrophy (BPH) patients, aiming to evaluate the association between the STR and increased risk for PCa. 120 PCa cases and 120 benign prostatic hypertrophy (BPH) cases were identified among participants. The region encompassing the TAAA repeat was amplified with a specific primer set we designed and screened by PCR-based cloning and sequencing in paired peripheral blood leukocytes and prostate tissues. Genotype-specific risks were estimated as odds ratios (ORs) associated with 95% confidence intervals (CIs) and adjusted for age by means of unconditional logistic regression. 5 PCA3 TAAA STR polymorphisms and 8 genotypes were found in both peripheral blood leukocytes and prostate tissues, the carriers with more TAAA repeats were associated with increased risk for PCa than individuals having less TAAA repeats. Interestingly, 18 (15.0%) of 120 PCa patients had more (TAAA)n repeats in prostate tissues than that in peripheral blood leukocytes, and 3 (2.5%) of 120 had less (TAAA)n repeats in prostate tissues. The results of this study suggest that short tandem repeat polymorphism of TAAA in the promoter region of PCA3 gene is a risk-increasing factor for prostate cancer in the Chinese population. In addition to the hereditary factor, the insertion mutation of (TAAA)n in a local tissue maybe another mechanism of the onset of PCa. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Influence of promoter/enhancer region haplotypes on MGMT transcriptional regulation: a potential biomarker for human sensitivity to alkylating agents.

    Science.gov (United States)

    Xu, Meixiang; Nekhayeva, Ilona; Cross, Courtney E; Rondelli, Catherine M; Wickliffe, Jeffrey K; Abdel-Rahman, Sherif Z

    2014-03-01

    The O6-methylguanine-DNA methyltransferase gene (MGMT) encodes the direct reversal DNA repair protein that removes alkyl adducts from the O6 position of guanine. Several single-nucleotide polymorphisms (SNPs) exist in the MGMT promoter/enhancer (P/E) region. However, the haplotype structure encompassing these SNPs and their functional/biological significance are currently unknown. We hypothesized that MGMT P/E haplotypes, rather than individual SNPs, alter MGMT transcription and can thus alter human sensitivity to alkylating agents. To identify the haplotype structure encompassing the MGMT P/E region SNPs, we sequenced 104 DNA samples from healthy individuals and inferred the haplotypes using the data generated. We identified eight SNPs in this region, namely T7C (rs180989103), T135G (rs1711646), G290A (rs61859810), C485A (rs1625649), C575A (rs113813075), G666A (rs34180180), C777A (rs34138162) and C1099T (rs16906252). Phylogenetics and Sequence Evolution analysis predicted 21 potential haplotypes that encompass these SNPs ranging in frequencies from 0.000048 to 0.39. Of these, 10 were identified in our study population as 20 paired haplotype combinations. To determine the functional significance of these haplotypes, luciferase reporter constructs representing these haplotypes were transfected into glioblastoma cells and their effect on MGMT promoter activity was determined. Compared with the most common (reference) haplotype 1, seven haplotypes significantly upregulated MGMT promoter activity (18-119% increase; P haplotype had no effect. Mechanistic studies conducted support the conclusion that MGMT P/E haplotypes, rather than individual SNPs, differentially regulate MGMT transcription and could thus play a significant role in human sensitivity to environmental and therapeutic alkylating agents.

  11. Regional efforts to promote forestry best management practices: a southern success story

    Science.gov (United States)

    Herb Nicholson; John Colberg; Hughes Simpson; Tom Gerow; Wib Owen

    2016-01-01

    The Southern Group of State Foresters has a long history of water resource protection efforts, providing leadership in BMP development, improvement, and implementation, enhancing state BMP programs, establishing effective partnerships, and standardizing an approach to consistently monitor implementation across the region.

  12. Promoting regional growth and innovation: relatedness, revealed comparative advantage and the product space

    NARCIS (Netherlands)

    Cicerone, Gloria; McCann, Philip; Venhorst, Viktor

    2017-01-01

    We adapt the product-space methodological approach of Hausmann and Klinger to the case of Italian provinces and regions in order to examine the extent to which the network connectedness and centrality of a province’s exports is related to its economic performance. We construct a new Product Space

  13. [Experimental proximal carpectomy. Biodynamics].

    Science.gov (United States)

    Kuhlmann, J N

    1992-01-01

    Proximal carpectomy was performed in 10 fresh cadavre wrists. Dynamic x-rays were taken and the forces necessary to obtain different movements before and after the operation were measured. Comparison of these parameters clearly defines the advantages and limitations of carpectomy and indicates the reasons.

  14. Proximate Analysis of Coal

    Science.gov (United States)

    Donahue, Craig J.; Rais, Elizabeth A.

    2009-01-01

    This lab experiment illustrates the use of thermogravimetric analysis (TGA) to perform proximate analysis on a series of coal samples of different rank. Peat and coke are also examined. A total of four exercises are described. These are dry exercises as students interpret previously recorded scans. The weight percent moisture, volatile matter,…

  15. Proximal Tibial Bone Graft

    Science.gov (United States)

    ... the Big Toe Ailments of the Smaller Toes Diabetic Foot Treatments Currently selected Injections and other Procedures Treatments ... from which the bone was taken if the foot/ankle surgeries done at the same time allow for it. ... problems after a PTBG include infection, fracture of the proximal tibia and pain related ...

  16. Sustained delivery of activated Rho GTPases and BDNF promotes axon growth in CSPG-rich regions following spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Anjana Jain

    2011-01-01

    Full Text Available Spinal cord injury (SCI often results in permanent functional loss. This physical trauma leads to secondary events, such as the deposition of inhibitory chondroitin sulfate proteoglycan (CSPG within astroglial scar tissue at the lesion.We examined whether local delivery of constitutively active (CA Rho GTPases, Cdc42 and Rac1 to the lesion site alleviated CSPG-mediated inhibition of regenerating axons. A dorsal over-hemisection lesion was created in the rat spinal cord and the resulting cavity was conformally filled with an in situ gelling hydrogel combined with lipid microtubes that slowly released constitutively active (CA Cdc42, Rac1, or Brain-derived neurotrophic factor (BDNF. Treatment with BDNF, CA-Cdc42, or CA-Rac1 reduced the number of GFAP-positive astrocytes, as well as CSPG deposition, at the interface of the implanted hydrogel and host tissue. Neurofilament 160kDa positively stained axons traversed the glial scar extensively, entering the hydrogel-filled cavity in the treatments with BDNF and CA-Rho GTPases. The treated animals had a higher percentage of axons from the corticospinal tract that traversed the CSPG-rich regions located proximal to the lesion site.Local delivery of CA-Cdc42, CA-Rac1, and BDNF may have a significant therapeutic role in overcoming CSPG-mediated regenerative failure after SCI.

  17. Promoting public-private mix for TB-DOTs: a multi-country study from the WHO Eastern Mediterranean Region.

    Science.gov (United States)

    Haq, Z; Khan, W; Seita, A

    2012-05-01

    This study was carried out to document the implementation status of public-private mix (PPM) in 6 member countries of the World Health Organization Eastern Mediterranean Region, with a particular focus on advocacy, communication and social mobilization (ACSM) specific to PPM. Interviews and focus group discussions were held with staff of national tuberculosis control programmes and partners. Four PPM models were being practised. For all models, ACSM specific to PPM was at the elementary stage. Participants perceived that promoting private partners was difficult, specific policy guidelines were deficient and human resources and capacity for both initiatives were lacking across the region. Building ACSM capacity is required along with the development of guidelines and the implementation of country-specific communication plans to carry out local-level advocacy, strategic communication and effective social mobilization to maximize the benefits of PPM.

  18. Meeting in the MIDDLE:BUILDING off Regional Policies to Promote Climate Education Partnerships on and off Campus

    Science.gov (United States)

    Griswold, M.; Stylinski, C.; Shea, N.; Veron, D. E.; Merrill, J.

    2013-12-01

    Both the impacts of climate change and the choices available to adapt and mitigate climate change largely function at the regional scale. Understanding and addressing climate change will require a concerted campaign involving a diverse array of educations from small to large organizations. By focusing on a specific region's climate impacts, adaptation and mitigation options, and existing policies, climate education networks will likely have a higher likelihood of sustainability. Building on this concept, we have developed a climate education partnership, Maryland Delaware Climate Change Education, Assessment and Research (MADE CLEAR), to better understand effective ways to support formal-, informal- and higher-education practitioners in climate change education in this Mid-Atlantic region. We do so largely through face-to-face and web based professional development for each education practitioner group to improve their capacity to incorporate rigorous regionally-based climate science and solutions into their education strategies. We are promoting communities-of-practice within and across these groups as they share their successes and challenges and consider common messages and approaches. Our training and resources focus on impacts and solutions most relevant to our region including sea level rise, extreme events, and urban heat impacts. Our professional development approach aligns directly with existing education and natural resource, including the region's environmental literacy initiatives, the Next Generation Science Standards, and state climate adaptation and mitigation plans. We anticipate that by building off of existing policy, we will build the success of the network into the future. Our project includes design-based research of all three education groups, and thus we will identify effective climate change education strategies, in and out of schools, that are applicable in other regions.

  19. Inter-organizational relations for regional development: an expansion policy promoted by the federal network of professional education, science & technology

    Directory of Open Access Journals (Sweden)

    Cleidson Nogueira Dias

    2014-12-01

    Full Text Available This research paper examines the importance of inter-organizational network management as a government policy tool to promote regional development. This pattern requires Federal Government intervention so as to compensate for the imbalance that this causes and to guarantee that economic growth resulting from government actions leads to development in all regions of the country, thereby avoiding the traditional mechanisms of wealth concentration. For this, a methodology of content analysis was used based on a relevant public policy aimed at promoting development within Brazil and by analyzing the data collected in relation to the current theory related to strategy, local development and inter-organizational networks in general.  The analysis results show that, when the policy studied in this work, applied in the federal network of professional education, science & technology, was implemented the networks had a positive influence on the outcome of the policy objectives and represented an extremely powerful support tool, being one of the most important factors to boost development.

  20. CAGE-defined promoter regions of the genes implicated in Rett Syndrome

    DEFF Research Database (Denmark)

    Vitezic, Morana; Bertin, Nicolas; Andersson, Robin

    2014-01-01

    BACKGROUND: Mutations in three functionally diverse genes cause Rett Syndrome. Although the functions of Forkhead box G1 (FOXG1), Methyl CpG binding protein 2 (MECP2) and Cyclin-dependent kinase-like 5 (CDKL5) have been studied individually, not much is known about their relation to each other...... for each gene and the common transcription factors likely to regulate the three genes. Our data imply Polycomb Repressive Complex 2 (PRC2) mediated silencing of Foxg1 in cerebellum CONCLUSIONS: Our analyses provide a comprehensive picture of the regulatory regions of the three genes involved in Rett...... Syndrome....

  1. Renal fibrosis: Primacy of the proximal tubule.

    Science.gov (United States)

    Gewin, Leslie S

    2018-02-06

    Tubulointerstitial fibrosis (TIF) is the hallmark of chronic kidney disease and best predictor of renal survival. Many different cell types contribute to TIF progression including tubular epithelial cells, myofibroblasts, endothelia, and inflammatory cells. Previously, most of the attention has centered on myofibroblasts given their central importance in extracellular matrix production. However, emerging data focuses on how the response of the proximal tubule, a specialized epithelial segment vulnerable to injury, plays a central role in TIF progression. Several proximal tubular responses such as de-differentiation, cell cycle changes, autophagy, and metabolic changes may be adaptive initially, but can lead to maladaptive responses that promote TIF both through autocrine and paracrine effects. This review discusses the current paradigm of TIF progression and the increasingly important role of the proximal tubule in promoting TIF both in tubulointerstitial and glomerular injuries. A better understanding and appreciation of the role of the proximal tubule in TIF has important implications for therapeutic strategies to halt chronic kidney disease progression. Copyright © 2017 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  2. Trithorax dependent changes in chromatin landscape at enhancer and promoter regions drive female puberty.

    Science.gov (United States)

    Toro, Carlos A; Wright, Hollis; Aylwin, Carlos F; Ojeda, Sergio R; Lomniczi, Alejandro

    2018-01-04

    Polycomb group (PcG) proteins control the timing of puberty by repressing the Kiss1 gene in hypothalamic arcuate nucleus (ARC) neurons. Here we identify two members of the Trithorax group (TrxG) of modifiers, mixed-lineage leukemia 1 (MLL1), and 3 (MLL3), as central components of an activating epigenetic machinery that dynamically counteracts PcG repression. Preceding puberty, MLL1 changes the chromatin configuration at the promoters of Kiss1 and Tac3, two genes required for puberty to occur, from repressive to permissive. Concomitantly, MLL3 institutes a chromatin structure that changes the functional status of a Kiss1 enhancer from poised to active. RNAi-mediated, ARC-specific Mll1 knockdown reduced Kiss1 and Tac3 expression, whereas CRISPR-Cas9-directed epigenome silencing of the Kiss1 enhancer selectively reduced Kiss1 activity. Both interventions delay puberty and disrupt reproductive cyclicity. Our results demonstrate that an epigenetic switch from transcriptional repression to activation is crucial to the regulatory mechanism controlling the timing of mammalian puberty.

  3. The Marche Film Commission: a Tool for Promoting Territorial Development and Regional Tourism

    Directory of Open Access Journals (Sweden)

    Enrico Nicosia

    2015-03-01

    Full Text Available The level of attractiveness of a tourist destination due to several tangible and intangible elements, which usually have a high degree of interdependence and reciprocity. The film is thus both a communication channel guide is a reference market of the destination. Many areas offer a wide variety of potential movie sets, thanks to the scenic splendor that characterizes different environmental and artistic and monumental heritage, also varied for the different origins of the architectural structures. This paper aims to highlight the role played by the Film Commission, which allow you to have a vision of cinema that goes beyond the original one, as they can think of it not only as a cultural activity, but also as a possible tool for development economic territory, able to promote and enhance the same resources and places of historical, artistic and natural and economic benefits are linked precisely to the revival of tourism and the possible revenues appropriated by the producers of the film/television industry.

  4. Replication of the TNFSF4 (OX40L) Promoter Region Association with Systemic Lupus Erythematosus

    Science.gov (United States)

    Delgado-Vega, Angélica M.; Abelson, Anna-Karin; Sánchez, Elena; Witte, Torsten; D’Alfonso, Sandra; Galeazzi, Mauro; Jiménez-Alonso, Juan; Pons-Estel, Bernardo A.

    2013-01-01

    The tumor necrosis factor ligand superfamily member 4 gene (TNFSF4) encodes the OX40 ligand (OX40L), a co-stimulatory molecule involved in T-cell activation. A recent study demonstrated the association ofTNFSF4 haplotypes located in the upstream region with risk for- or protection from Systemic Lupus Erythematosus (SLE) (Graham et al, 2008). In order to replicate this association, five single nucleotide polymorphisms (SNPs) tagging the previously associated haplotypes and passing the proper quality control filters were tested in 1312 cases and 1801 controls from Germany, Italy, Spain, and Argentina. The association of TNFSF4 with SLE was replicated in all the sets except Spain. There was a unique risk haplotype tagged by the minor alleles of the SNPs rs1234317 (pooled OR=1.39, p=0.0009) and rs12039904 (pooled OR=1.38, p=0.0012). We did not observe association to a single protective marker (rs844644) or haplotype as the first study reported; instead, we observed different protective haplotypes, all carrying the major alleles of both SNPs rs1234317 and rs12039904. Association analysis conditioning on the haplotypic background confirmed that these two SNPs explain the entire haplotype effect. This is the first replication study that confirms the association of genetic variation in the upstream region of TNFSF4 with susceptibility to SLE. PMID:19092840

  5. Gene promoter evolution targets the center of the human protein interaction network.

    Directory of Open Access Journals (Sweden)

    Jordi Planas

    Full Text Available Assessing the contribution of promoters and coding sequences to gene evolution is an important step toward discovering the major genetic determinants of human evolution. Many specific examples have revealed the evolutionary importance of cis-regulatory regions. However, the relative contribution of regulatory and coding regions to the evolutionary process and whether systemic factors differentially influence their evolution remains unclear. To address these questions, we carried out an analysis at the genome scale to identify signatures of positive selection in human proximal promoters. Next, we examined whether genes with positively selected promoters (Prom+ genes show systemic differences with respect to a set of genes with positively selected protein-coding regions (Cod+ genes. We found that the number of genes in each set was not significantly different (8.1% and 8.5%, respectively. Furthermore, a functional analysis showed that, in both cases, positive selection affects almost all biological processes and only a few genes of each group are located in enriched categories, indicating that promoters and coding regions are not evolutionarily specialized with respect to gene function. On the other hand, we show that the topology of the human protein network has a different influence on the molecular evolution of proximal promoters and coding regions. Notably, Prom+ genes have an unexpectedly high centrality when compared with a reference distribution (P=0.008, for Eigenvalue centrality. Moreover, the frequency of Prom+ genes increases from the periphery to the center of the protein network (P=0.02, for the logistic regression coefficient. This means that gene centrality does not constrain the evolution of proximal promoters, unlike the case with coding regions, and further indicates that the evolution of proximal promoters is more efficient in the center of the protein network than in the periphery. These results show that proximal promoters

  6. Gene Promoter Evolution Targets the Center of the Human Protein Interaction Network

    Science.gov (United States)

    Planas, Jordi; Serrat, Josep M.

    2010-01-01

    Assessing the contribution of promoters and coding sequences to gene evolution is an important step toward discovering the major genetic determinants of human evolution. Many specific examples have revealed the evolutionary importance of cis-regulatory regions. However, the relative contribution of regulatory and coding regions to the evolutionary process and whether systemic factors differentially influence their evolution remains unclear. To address these questions, we carried out an analysis at the genome scale to identify signatures of positive selection in human proximal promoters. Next, we examined whether genes with positively selected promoters (Prom+ genes) show systemic differences with respect to a set of genes with positively selected protein-coding regions (Cod+ genes). We found that the number of genes in each set was not significantly different (8.1% and 8.5%, respectively). Furthermore, a functional analysis showed that, in both cases, positive selection affects almost all biological processes and only a few genes of each group are located in enriched categories, indicating that promoters and coding regions are not evolutionarily specialized with respect to gene function. On the other hand, we show that the topology of the human protein network has a different influence on the molecular evolution of proximal promoters and coding regions. Notably, Prom+ genes have an unexpectedly high centrality when compared with a reference distribution (P = 0.008, for Eigenvalue centrality). Moreover, the frequency of Prom+ genes increases from the periphery to the center of the protein network (P = 0.02, for the logistic regression coefficient). This means that gene centrality does not constrain the evolution of proximal promoters, unlike the case with coding regions, and further indicates that the evolution of proximal promoters is more efficient in the center of the protein network than in the periphery. These results show that proximal promoters have

  7. Evaluation of a novel multi-immunogen vaccine strategy for targeting 4E10/10E8 neutralizing epitopes on HIV-1 gp41 membrane proximal external region.

    Science.gov (United States)

    Banerjee, Saikat; Shi, Heliang; Banasik, Marisa; Moon, Hojin; Lees, William; Qin, Yali; Harley, Andrew; Shepherd, Adrian; Cho, Michael W

    2017-05-01

    The membrane proximal external region (MPER) of HIV-1 gp41 is targeted by broadly neutralizing antibodies (bnAbs) 4E10 and 10E8. In this proof-of-concept study, we evaluated a novel multi-immunogen vaccine strategy referred to as Incremental, Phased Antigenic Stimulation for Rapid Antibody Maturation (IPAS-RAM) to induce 4E10/10E8-like bnAbs. Rabbits were immunized sequentially, but in a phased manner, with three immunogens that are progressively more native (gp41-28×3, gp41-54CT, and rVV-gp160DH12). Although nAbs were not induced, epitope-mapping analyses indicated that IPAS-RAM vaccination was better able to target antibodies towards the 4E10/10E8 epitopes than homologous prime-boost immunization using gp41-28×3 alone. MPER-specific rabbit monoclonal antibodies were generated, including 9F6. Although it lacked neutralizing activity, the target epitope profile of 9F6 closely resembled those of 4E10 and 10E8 ((671)NWFDITNWLWYIK(683)). B-cell repertoire analyses suggested the importance of co-immunizations for maturation of 9F6, which warrants further evaluation of our IPAS-RAM vaccine strategy using an improved priming immunogen. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Proximal humeral fractures

    OpenAIRE

    Mauro, Craig S.

    2011-01-01

    Proximal humeral fractures may present with many different configurations in patients with varying co-morbities and expectations. As a result, the treating physician must understand the fracture pattern, the quality of the bone, other patient-related factors, and the expanding range of reconstructive options to achieve the best functional outcome and to minimize complications. Current treatment options range from non-operative treatment with physical therapy to fracture fixation using percuta...

  9. Differential DNA methylation of microRNAs within promoters, intergenic and intragenic regions of type 2 diabetic, pre-diabetic and non-diabetic individuals.

    Science.gov (United States)

    Pheiffer, Carmen; Erasmus, Rajiv T; Kengne, Andre P; Matsha, Tandi E

    2016-04-01

    Accumulating evidence supports the role of epigenetic modifications, and in particular DNA methylation and non-coding RNAs in the pathophysiology of type 2 diabetes. Alterations in methylation patterns within promoter regions are linked with aberrant transcription and pathological gene expression; however the role of methylation within non-promoter regions is not yet fully elucidated. We performed whole genome methylated DNA immunoprecipitation sequencing (MeDIP-Seq) in peripheral-blood-derived DNA from age-gender-body mass index (BMI)-ethnicity matched type 2 diabetic, pre-diabetic and non-diabetic individuals. The density of methylation normalized to the average length of the promoter, intergenic and intragenic regions and to CpG count was 3.17, 9.80 and 0.09 for the promoter, intergenic and intragenic regions, respectively. Methylation within these regions varied according to glucose tolerance status and was associated with hypermethylation rather than hypomethylation. MicroRNA-DNA methylation peaks accounted for 4.8% of the total number of peaks detected. Differential DNA methylation of these microRNA peaks was observed during dysglycemia, with the promoter, intergenic and intragenic regions accounting for 2%, 95% and 3% respectively, of the differentially methylated microRNA peaks. Genome-wide DNA methylation varied according to glucose tolerance. Methylation within non-promoter regions accounted for the majority of differentially methylated peaks identified, thus highlighting the importance of DNA methylation within these non-promoter regions in the pathogenesis of type 2 diabetes. This study suggests that DNA methylation within intergenic regions is a mechanism regulating microRNAs, another increasingly important epigenetic factor, during type 2 diabetes. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  10. Increased fire frequency promotes stronger spatial genetic structure and natural selection at regional and local scales in Pinus halepensis Mill.

    Science.gov (United States)

    Budde, Katharina B; González-Martínez, Santiago C; Navascués, Miguel; Burgarella, Concetta; Mosca, Elena; Lorenzo, Zaida; Zabal-Aguirre, Mario; Vendramin, Giovanni G; Verdú, Miguel; Pausas, Juli G; Heuertz, Myriam

    2017-04-01

    The recurrence of wildfires is predicted to increase due to global climate change, resulting in severe impacts on biodiversity and ecosystem functioning. Recurrent fires can drive plant adaptation and reduce genetic diversity; however, the underlying population genetic processes have not been studied in detail. In this study, the neutral and adaptive evolutionary effects of contrasting fire regimes were examined in the keystone tree species Pinus halepensis Mill. (Aleppo pine), a fire-adapted conifer. The genetic diversity, demographic history and spatial genetic structure were assessed at local (within-population) and regional scales for populations exposed to different crown fire frequencies. Eight natural P. halepensis stands were sampled in the east of the Iberian Peninsula, five of them in a region exposed to frequent crown fires (HiFi) and three of them in an adjacent region with a low frequency of crown fires (LoFi). Samples were genotyped at nine neutral simple sequence repeats (SSRs) and at 251 single nucleotide polymorphisms (SNPs) from coding regions, some of them potentially important for fire adaptation. Fire regime had no effects on genetic diversity or demographic history. Three high-differentiation outlier SNPs were identified between HiFi and LoFi stands, suggesting fire-related selection at the regional scale. At the local scale, fine-scale spatial genetic structure (SGS) was overall weak as expected for a wind-pollinated and wind-dispersed tree species. HiFi stands displayed a stronger SGS than LoFi stands at SNPs, which probably reflected the simultaneous post-fire recruitment of co-dispersed related seeds. SNPs with exceptionally strong SGS, a proxy for microenvironmental selection, were only reliably identified under the HiFi regime. An increasing fire frequency as predicted due to global change can promote increased SGS with stronger family structures and alter natural selection in P. halepensis and in plants with similar life history traits.

  11. Revolutionising engineering education in the Middle East region to promote earthquake-disaster mitigation

    Science.gov (United States)

    Baytiyeh, Hoda; Naja, Mohamad K.

    2014-09-01

    Due to the high market demands for professional engineers in the Arab oil-producing countries, the appetite of Middle Eastern students for high-paying jobs and challenging careers in engineering has sharply increased. As a result, engineering programmes are providing opportunities for more students to enrol on engineering courses through lenient admission policies that do not compromise academic standards. This strategy has generated an influx of students who must be carefully educated to enhance their professional knowledge and social capital to assist in future earthquake-disaster risk-reduction efforts. However, the majority of Middle Eastern engineering students are unaware of the valuable acquired engineering skills and knowledge in building the resilience of their communities to earthquake disasters. As the majority of the countries in the Middle East are exposed to seismic hazards and are vulnerable to destructive earthquakes, engineers have become indispensable assets and the first line of defence against earthquake threats. This article highlights the contributions of some of the engineering innovations in advancing technologies and techniques for effective disaster mitigation and it calls for the incorporation of earthquake-disaster-mitigation education into academic engineering programmes in the Eastern Mediterranean region.

  12. DNA methylation patterns of behavior-related gene promoter regions dissect the gray wolf from domestic dog breeds.

    Science.gov (United States)

    Banlaki, Zsofia; Cimarelli, Giulia; Viranyi, Zsofia; Kubinyi, Eniko; Sasvari-Szekely, Maria; Ronai, Zsolt

    2017-06-01

    A growing body of evidence highlights the relationship between epigenetics, especially DNA methylation, and population divergence as well as speciation. However, little is known about how general the phenomenon of epigenetics-wise separation of different populations is, or whether population assignment is, possible based on solely epigenetic marks. In the present study, we compared DNA methylation profiles between four different canine populations: three domestic dog breeds and their ancestor the gray wolf. Altogether, 79 CpG sites constituting the 65 so-called CpG units located in the promoter regions of genes affecting behavioral and temperamental traits (COMT, HTR1A, MAOA, OXTR, SLC6A4, TPH1, WFS1)-regions putatively targeted during domestication and breed selection. Methylation status of buccal cells was assessed using EpiTYPER technology. Significant inter-population methylation differences were found in 52.3% of all CpG units investigated. DNA methylation profile-based hierarchical cluster analysis indicated an unambiguous segregation of wolf from domestic dog. In addition, one of the three dog breeds (Golden Retriever) investigated also formed a separate, autonomous group. The findings support that population segregation is interrelated with shifts in DNA methylation patterns, at least in putative selection target regions, and also imply that epigenetic profiles could provide a sufficient basis for population assignment of individuals.

  13. THE ANALYSIS OF THE ASYMMETRICAL RISK IN TOURISM FOR THE DEVELOPMENT AND PROMOTION OF A LASTING REGIONAL TOURISM IDENTITY

    Directory of Open Access Journals (Sweden)

    Alexandru NEDELEA

    2009-06-01

    Full Text Available In order to establish an adequate balance between tourists' welfare, the needs of the natural and cultural environment, as well as to develop tourist destinations and organizations' competitiveness, it is necessary to carry out a global and integrated approach, where all interested parties share the same goals regarding the durability of tourism and the approached challenges. The purpose of this work is to identify the factors of reduced risk having a major impact over the sustainability of the tourist region under analysis and to highlight the risk factors' connections and impact in order to minimize and eliminate them, with direct effects over the awareness of tourist industry's values. The identification of lasting development's indicators will take into account all these three aspects of the durable development of tourism, namely ecological, economical and social factors, that play a part in highlighting the real performance of a tourist destination. All these aspects are absolutely necessary for the promotion of the Danube's tourist potential, achievable through the emphasis of the relevant values from the tourist patrimony of the county of Galati. The promotion of the Danube' tourist potential presupposes a series of objectives that are subordinated to the general direction that is marked at the national level, respectively Romania's transformation into a qualitative tourist destination based on its natural and cultural patrimony, in order to correspond to the European Union standards. The new policy regarding tourism proposed by the European Commission aims at offering constant support for this industry to be able to face different challenges, by promoting also competitiveness in general.

  14. New Variations in the Promoter Regions of Human DOCK4 and RAP1A Genes, and Coding Regions of RAP1A in Sporadic Breast Tumors.

    Science.gov (United States)

    Jalali, Akram; Ebrahimi, Hassan; Ohadi, Mina; Karimloo, Masood; Shemirani, Atena Irani; Mohajer, Behrokh; Khorshid, Hamid Reza Khorram

    2009-07-01

    Breast cancer is the most common cancer among women in developed countries. The prevalence of the disease is increasing in the world. Its annual incidence among Iranian women is about 7000 cases. RAP1A, a tumor suppressor gene, is located at 1p13.3 and plays an important role in the cellular adhesion pathway and is involved in the pathogenesis of breast cancer. The DOCK4 gene, which is located at 7q31.1, specifically activates RAP1A gene. In the present study, DNA samples from 64 cases of sporadic breast tumors (referred to Mehrad Hospital in Tehran) were screened using PCR-SSCP method and the number of observed variations compared with the control group (100 normal women). Mutation detection for coding exons of RAP1A gene and the 500 bp upstream of transcription initiation site as promoters of both DOCK4 and RAP1A were carried out and compared with the control group. The promoter region of DOCK4 showed a heterozygous mutation with G>A transition at nucleotide -303 in a fibroadenoma case. With regard to RAP1A we found a heterozygous mutation, G>A transition in an adenoid cystic carcinoma case, and another heterozygous mutation, G>T transversion in an intraductal papilloma case both at nucleotide +45. A homozygous variation, T>A transversion was also found at nucleotide +29 of a fibroadenoma case. The differences in the frequency of variations mentioned above were not statistically significant. However Fisher's exact showed significant difference for T>A transversion. Although, the higher frequency of these mutations and variations may be related to the disease, a larger sample size is needed for the confirmation of our findings.

  15. Development of a novel data mining tool to find cis-elements in rice gene promoter regions

    Directory of Open Access Journals (Sweden)

    Mendoza Michael J

    2008-02-01

    Full Text Available Abstract Background Information on more than 35 000 full-length Oryza sativa cDNAs, together with associated microarray gene expression data collected under various treatment conditions, has made it feasible to identify motifs that are conserved in gene promoters and may act as cis-regulatory elements with key roles under the various conditions. Results We have developed a novel tool that searches for cis-element candidates in the upstream, downstream, or coding regions of differentially regulated genes. The tool first lists cis-element candidates by motif searching based on the supposition that if there are cis-elements playing important roles in the regulation of a given set of genes, they will be statistically overrepresented and will be conserved. Then it evaluates the likelihood scores of the listed candidate motifs by association rule analysis. This strategy depends on the idea that motifs overrepresented in the promoter region could play specific roles in the regulation of expression of these genes. The tool is designed so that any biological researchers can use it easily at the publicly accessible Internet site http://hpc.irri.cgiar.org/tool/nias/ces. We evaluated the accuracy and utility of the tool by using a dataset of auxin-inducible genes that have well-studied cis-elements. The test showed the effectiveness of the tool in identifying significant relationships between cis-element candidates and related sets of genes. Conclusion The tool lists possible cis-element motifs corresponding to genes of interest, and it will contribute to the deeper understanding of gene regulatory mechanisms in plants.

  16. High fructose consumption induces DNA methylation at PPARα and CPT1A promoter regions in the rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Ohashi, Koji [Department of Clinical Biochemistry, Fujita Health University School of Health Sciences, Toyoake (Japan); Munetsuna, Eiji [Department of Biochemistry, Fujita Health University School of Medicine, Toyoake (Japan); Yamada, Hiroya, E-mail: hyamada@fujita-hu.ac.jp [Department of Hygiene, Fujita Health University School of Medicine, Toyoake (Japan); Ando, Yoshitaka [Department of Joint Research Laboratory of Clinical Medicine, Fujita Health University Hospital, Toyoake (Japan); Yamazaki, Mirai; Taromaru, Nao; Nagura, Ayuri; Ishikawa, Hiroaki [Department of Clinical Biochemistry, Fujita Health University School of Health Sciences, Toyoake (Japan); Suzuki, Koji [Department of Public Health, Fujita Health University School of Health Sciences, Toyoake (Japan); Teradaira, Ryoji [Department of Clinical Biochemistry, Fujita Health University School of Health Sciences, Toyoake (Japan); Hashimoto, Shuji [Department of Hygiene, Fujita Health University School of Medicine, Toyoake (Japan)

    2015-12-04

    DNA methylation status is affected by environmental factors, including nutrition. Fructose consumption is considered a risk factor for the conditions that make up metabolic syndrome such as dyslipidemia. However, the pathogenetic mechanism by which fructose consumption leads to metabolic syndrome is unclear. Based on observations that epigenetic modifications are closely related to induction of metabolic syndrome, we hypothesized that fructose-induced metabolic syndrome is caused by epigenetic alterations. Male SD rats were designated to receive water or 20% fructose solution for 14 weeks. mRNA levels for peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase 1A (CPT1A) was analyzed using Real-time PCR. Restriction digestion and real-time PCR (qAMP) was used for the analysis of DNA methylation status. Hepatic lipid accumulation was also observed by fructose intake. Fructose feeding also significantly decreased mRNA levels for PPARα and CPT1A. qAMP analysis demonstrated the hypermethylation of promoter regions of PPARα and CTP1A genes. Fructose-mediated attenuated gene expression may be mediated by alterations of DNA methylation status, and pathogenesis of metabolic syndrome induced by fructose relates to DNA methylation status. - Highlights: • No general consensus has been reached regarding the molecular mechanisms of the pathogenesis of fructose-induced diseases. • Significant increase in hepatic total methylation level was observed after fructose-supplemented feeding. • Fructose feeding significantly decreased mRNA levels for PPARα and CPT1A. • qAMP analysis demonstrated the hypermethylation of promoter regions of PPARα and CTP1A genes. • Fructose-mediated attenuated gene expression may be mediated by alterations of DNA methylation status in rat liver.

  17. Developing Integrated Object-Oriented Conception of Geomarketing as a Tool for Promotion of Regional Sustainable Development: The Case Study of Ukraine

    OpenAIRE

    Volodymyr Anderson

    2004-01-01

    In the paper we propose and discuss new vision of geomarketing as a tool for promotion of regional sustainable development. Integrated object-oriented conception of geomarketing was designed by adoption and elaboration of some new ideas and approaches, such as “place marketing”, “non-profit marketing”, “counter-marketing”, “collaborative spatial decision-making”, “endogenous regional development”, “regional sustainable development”, “public-private partnership”. We explore how geomarketing in...

  18. The UGA3-GLT1 intergenic region constitutes a promoter whose bidirectional nature is determined by chromatin organization in Saccharomyces cerevisiae.

    Science.gov (United States)

    Ishida, Cecilia; Aranda, Cristina; Valenzuela, Lourdes; Riego, Lina; Deluna, Alexander; Recillas-Targa, Félix; Filetici, Patrizia; López-Revilla, Rubén; González, Alicia

    2006-03-01

    Transcription of an important number of divergent genes of Saccharomyces cerevisiae is controlled by intergenic regions, which constitute factual bidirectional promoters. However, few of such promoters have been characterized in detail. The analysis of the UGA3-GLT1 intergenic region has provided an interesting model to study the joint action of two global transcriptional activators that had been considered to act independently. Our results show that Gln3p and Gcn4p exert their effect upon cis-acting elements, which are shared in a bidirectional promoter. Accordingly, when yeast is grown on a low-quality nitrogen source, or under amino acid deprivation, the expression of both UGA3 and GLT1 is induced through the action of both these global transcriptional modulators that bind to a region of the bidirectional promoter. In addition, we demonstrate that chromatin organization plays a major role in the bidirectional properties of the UGA3-GLT1 promoter, through the action of an upstream Abf1p-binding consensus sequence and a polydAdT(tract). Mutations in these cis-elements differentially affect transcription of UGA3 and GLT1, and thus alter the overall relative expression. This is the first example of an intergenic region constituting a promoter whose bidirectional character is determined by chromatin organization.

  19. Systematic screening for mutations in the promoter and the coding region of the 5-HT{sub 1A} gene

    Energy Technology Data Exchange (ETDEWEB)

    Erdmann, J.; Shimron-Abarbanell, D.; Cichon, S. [Univ. of Bonn (Germany)] [and others

    1995-10-09

    In the present study we sought to identify genetic variation in the 5-HT{sub 1A} receptor gene which through alteration of protein function or level of expression might contribute to the genetic predisposition to neuropsychiatric diseases. Genomic DNA samples from 159 unrelated subjects (including 45 schizophrenic, 46 bipolar affective, and 43 patients with Tourette`s syndrome, as well as 25 healthy controls) were investigated by single-strand conformation analysis. Overlapping PCR (polymerase chain reaction) fragments covered the whole coding sequence as well as the 5{prime} untranslated region of the 5-HT{sub 1A} gene. The region upstream to the coding sequence we investigated contains a functional promoter. We found two rare nucleotide sequence variants. Both mutations are located in the coding region of the gene: a coding mutation (A{yields}G) in nucleotide position 82 which leads to an amino acid exchange (Ile{yields}Val) in position 28 of the receptor protein and a silent mutation (C{yields}T) in nucleotide position 549. The occurrence of the Ile-28-Val substitution was studied in an extended sample of patients (n = 352) and controls (n = 210) but was found in similar frequencies in all groups. Thus, this mutation is unlikely to play a significant role in the genetic predisposition to the diseases investigated. In conclusion, our study does not provide evidence that the 5-HT{sub 1A} gene plays either a major or a minor role in the genetic predisposition to schizophrenia, bipolar affective disorder, or Tourette`s syndrome. 29 refs., 4 figs., 1 tab.

  20. Weak correlation between sequence conservation in promoter regions and in protein-coding regions of human-mouse orthologous gene pairs

    Directory of Open Access Journals (Sweden)

    Nakai Kenta

    2008-04-01

    Full Text Available Abstract Background Interspecies sequence comparison is a powerful tool to extract functional or evolutionary information from the genomes of organisms. A number of studies have compared protein sequences or promoter sequences between mammals, which provided many insights into genomics. However, the correlation between protein conservation and promoter conservation remains controversial. Results We examined promoter conservation as well as protein conservation for 6,901 human and mouse orthologous genes, and observed a very weak correlation between them. We further investigated their relationship by decomposing it based on functional categories, and identified categories with significant tendencies. Remarkably, the 'ribosome' category showed significantly low promoter conservation, despite its high protein conservation, and the 'extracellular matrix' category showed significantly high promoter conservation, in spite of its low protein conservation. Conclusion Our results show the relation of gene function to protein conservation and promoter conservation, and revealed that there seem to be nonparallel components between protein and promoter sequence evolution.

  1. Characterization of five evolutionary conserved regions of the human tyrosine hydroxylase (TH) promoter: implications for the engineering of a human TH minimal promoter assembled in a self-inactivating lentiviral vector system.

    Science.gov (United States)

    Romano, Gaetano; Suon, Sokreine; Jin, Hao; Donaldson, Angela E; Iacovitti, Lorraine

    2005-08-01

    A DNA fragment of about 13 kb containing the human tyrosine hydroxylase (TH) promoter was previously isolated from a genomic DNA library and sequenced. The 11 kb from the transcription start of the human TH promoter was successively joined to the green fluorescent protein (GFP) to generate a transgenic mouse model. High levels of GFP expression could be observed in TH-positive cells of the Substantia nigra of embryonic and adult mice. Intriguingly, the sequence of the human TH promoter showed a low degree of homology with the mouse and rat TH promoters. In fact, comparative analysis of the sequences of human, rat, and mouse TH promoters revealed only five small regions of high homology. These five evolutionarily conserved regions were numbered in numeric progression from the 5' end of human TH promoter. In the present study, a panel of minimal human TH promoters was generated to analyze the transcriptional activity and specificity of gene expression conferred by the five conserved regions (CRs). The series of constructs was termed 250 bp and contained the first -194 bp of the human TH promoter immediately upstream of the transcription start, the first 35 bp the human TH messenger RNA leader, plus one or more of the five CRs. All the constructs were assembled in a self-inactivating form of the latest series of lentiviral vector system based on the human immunodeficiency virus type 1 (HIV-1). Lentiviral-mediated gene transfer was highly efficient for the in vitro transduction of human neuronal progenitor cells (hNPCs). Since a subset of hNPCs express TH following in vitro treatment with a mixture of differentiating agents, it was possible to assess specificity of expression for all the minimal human TH promoters. Overall, the successive addition of the five conserved regions produced a greater degree of specificity in induced TH-positive hNPCs, in particular after the addition of CRI (-8,917, -8,876). However, the human TH minimal promoters did not show any

  2. A triple stranded G-quadruplex formation in the promoter region of human myosin β(Myh7) gene.

    Science.gov (United States)

    Singh, Anju; Kukreti, Shrikant

    2017-09-19

    Regulatory regions in human genome, enriched in guanine-rich DNA sequences have the propensity to fold into G-quadruplex structures. On exploring the genome for search of G-tracts, it was interesting to find that promoter of Human Myosin Gene (MYH7) contains a conserved 23-mer G-rich sequence (HM-23). Mutations in this gene are associated with familial cardiomyopathy. Enrichment of MYH7 gene in G-rich sequences could possibly play a critical role in its regulation. We used polyacrylamide gel electrophoresis (PAGE), UV-Thermal denaturation (UV-Tm) and Circular Dichroism (CD), to demonstrate the formation of a G-quadruplex by 23-mer G-rich sequence HM23 in promoter location of MYH7 gene. We observed that the wild G-rich sequence HM23 containing consecutive G5 stretch in two stacks adopt G-quadruplexes of diverse molecularity by involvement of four-strand, three-strand and two-strands with same parallel topology. Interestingly, the mutated sequence in the absence of continuous G5 stretch obstructs the formation of three-stranded G-quadruplex. We demonstrated that continuous G5 stretch is mandatory for the formation of a unique three-stranded G-quadruplex. Presence of various transcription factors (TF) in vicinity of the sequence HM23 leave fair possibility of recognition by TF binding sites, and so modulate gene expression. These findings may add on our understanding about the effect of base change in the formation of varied structural species in similar solution condition. This study may give insight about structural polymorphism arising due to recognition of non-Watson-Crick G-quadruplex structures by cellular proteins and designing structure specific molecules.

  3. Some Properties of Fuzzy Soft Proximity Spaces

    Science.gov (United States)

    Demir, İzzettin; Özbakır, Oya Bedre

    2015-01-01

    We study the fuzzy soft proximity spaces in Katsaras's sense. First, we show how a fuzzy soft topology is derived from a fuzzy soft proximity. Also, we define the notion of fuzzy soft δ-neighborhood in the fuzzy soft proximity space which offers an alternative approach to the study of fuzzy soft proximity spaces. Later, we obtain the initial fuzzy soft proximity determined by a family of fuzzy soft proximities. Finally, we investigate relationship between fuzzy soft proximities and proximities. PMID:25793224

  4. Histone deacetylase inhibition modulates histone acetylation at gene promoter regions and affects genome-wide gene transcription in Schistosoma mansoni.

    Directory of Open Access Journals (Sweden)

    Letícia Anderson

    2017-04-01

    Full Text Available Schistosomiasis is a parasitic disease infecting hundreds of millions of people worldwide. Treatment depends on a single drug, praziquantel, which kills the Schistosoma spp. parasite only at the adult stage. HDAC inhibitors (HDACi such as Trichostatin A (TSA induce parasite mortality in vitro (schistosomula and adult worms, however the downstream effects of histone hyperacetylation on the parasite are not known.TSA treatment of adult worms in vitro increased histone acetylation at H3K9ac and H3K14ac, which are transcription activation marks, not affecting the unrelated transcription repression mark H3K27me3. We investigated the effect of TSA HDACi on schistosomula gene expression at three different time points, finding a marked genome-wide change in the transcriptome profile. Gene transcription activity was correlated with changes on the chromatin acetylation mark at gene promoter regions. Moreover, combining expression data with ChIP-Seq public data for schistosomula, we found that differentially expressed genes having the H3K4me3 mark at their promoter region in general showed transcription activation upon HDACi treatment, compared with those without the mark, which showed transcription down-regulation. Affected genes are enriched for DNA replication processes, most of them being up-regulated. Twenty out of 22 genes encoding proteins involved in reducing reactive oxygen species accumulation were down-regulated. Dozens of genes encoding proteins with histone reader motifs were changed, including SmEED from the PRC2 complex. We targeted SmEZH2 methyltransferase PRC2 component with a new EZH2 inhibitor (GSK343 and showed a synergistic effect with TSA, significantly increasing schistosomula mortality.Genome-wide gene expression analyses have identified important pathways and cellular functions that were affected and may explain the schistosomicidal effect of TSA HDACi. The change in expression of dozens of histone reader genes involved in

  5. PROXIMITY MANAGEMENT IN CRISIS CONDITIONS

    Directory of Open Access Journals (Sweden)

    Ion Dorin BUMBENECI

    2010-01-01

    Full Text Available The purpose of this study is to evaluate the level of assimilation for the terms "Proximity Management" and "Proximity Manager", both in the specialized literature and in practice. The study has two parts: the theoretical research of the two terms, and an evaluation of the use of Proximity management in 32 companies in Gorj, Romania. The object of the evaluation resides in 27 companies with less than 50 employees and 5 companies with more than 50 employees.

  6. The LTR promoter of the rat oncomodulin gene is regulated by cell-line specific accessibility in the LTR U3 region

    DEFF Research Database (Denmark)

    Rentsch, J. M.; Hergersberg, M.; Banville, D.

    2006-01-01

    mechanisms of LTR directed OM gene expression we tested promoter activity of this LTR by transient transfection of transformed rat fibroblasts with this sequence placed 5' of the human growth hormone hGH reporter gene. The OM LTR is a strong promoter but does not follow an expression pattern similar...... located within the U3 region of the LTR element. Several cis-elements in the OM LTR promoter exhibiting cell-line specific occupancy were identified by in vivo DMS-footprinting. Detailed analysis of protein interactions with two such sequence elements in vitro revealed binding of ubiquitously expressed...

  7. Effects of boiling and roasting on proximate composition, lipid oxidation, fatty acid profile and mineral content of two sesame varieties commercialized and consumed in Far-North Region of Cameroon.

    Science.gov (United States)

    Tenyang, Noël; Ponka, Roger; Tiencheu, Bernard; Djikeng, Fabrice T; Azmeera, Thirupathi; Karuna, Mallampalli S L; Prasad, Rachapudi B N; Womeni, Hilaire M

    2017-04-15

    The aim of this study was to determine the effect of boiling and roasting on the proximate, lipid oxidation, fatty acid profile and mineral content of two sesame seeds varieties. The proximate composition was significantly affected (Psesame oil after processing was significantly increased (Psesame varieties. C16:0, C18:0, C18:1 and C18:2 were quantitatively the most important fatty acids in sesame oil. Boiling appeared to be the best processing method for cooking the two sesame varieties concerning oxidative stability and fatty acid profile. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Polymorphism of the promoter region and exon 1 of the CTLA4 gene in endemic pemphigus foliaceus (fogo selvagem

    Directory of Open Access Journals (Sweden)

    D.P. Pavoni

    2006-09-01

    Full Text Available Endemic pemphigus foliaceus (EPF is an autoimmune bullous skin disease characterized by acantholysis and antibodies against a desmosomal protein, desmoglein 1. Genetic and environmental factors contribute to development of this multifactorial disease. HLA class II and some cytokine gene polymorphisms are the only genetic markers thus far known to be associated with susceptibility to or protection from EPF. The cytotoxic T-lymphocyte antigen-4 gene (CTLA4 encodes a key immunoreceptor molecule that regulates and inhibits T-cell proliferation. It participates in the regulatory process controlling autoreactivity and therefore has been considered a strong candidate gene in autoimmune diseases. In the search for genes that might influence EPF pathogenesis, we analyzed variants of the CTLA4 gene in a sample of 118 patients and 291 controls from a Brazilian population. This is the first study investigating the possible role of polymorphisms of the 2q33 chromosomal region in differential susceptibility to pemphigus foliaceus. Promoter region and exon 1 single nucleotide polymorphisms -318 (C,T and 49 (A,G were genotyped using sequence-specific oligonucleotide probes after amplification by the polymerase chain reaction. The allelic and genotypic frequencies did not differ significantly between the patient and the control groups (-318T: 9.8 and 10.9%, 49G: 33.0 and 35.2% were the allelic frequencies in patients and controls, respectively. In addition, no significant difference was found when the patient and control population samples were stratified by the presence of HLA-DRB1 alleles. We conclude that the CTLA4 -318 (C,T and 49 (A,G polymorphisms do not play a major role in EPF development.

  9. Diversity of CTX-M beta-lactamases and their promoter regions from Enterobacteriaceae isolated in three Parisian hospitals.

    Science.gov (United States)

    Saladin, Michèle; Cao, Van Thi Bao; Lambert, Thierry; Donay, Jean-Luc; Herrmann, Jean-Louis; Ould-Hocine, Zahia; Verdet, Charlotte; Delisle, Françoise; Philippon, Alain; Arlet, Guillaume

    2002-04-09

    Nine clinical isolates of Enterobacteriaceae (six Escherichia coli and three Proteus mirabilis) isolated in three Parisian hospitals between 1989 and 2000 showed a particular extended-spectrum cephalosporin-resistance profile characterized by resistance to cefotaxime and aztreonam but not to ceftazidime. CTX-M-1, CTX-M-2, CTX-M-9, CTX-M-14 and two novel plasmid-mediated CTX-M beta-lactamases (CTX-M-20, and CTX-M-21) were identified by polymerase chain reaction and isoelectric focusing (pI>8) and were associated in eight cases with TEM-1 (pI=5.4) or TEM-2 (pI=5.6) beta-lactamases. We used internal ISEcp1 and IS26 forward primers and the CTX-M consensus reverse primer to characterize the CTX-M beta-lactamase promoter regions and showed their high degree of structure diversity. We found upstream of some bla(CTX-M) genes, a 266-bp sequence 100% identical to the sequence upstream of the Kluyvera ascorbata beta-lactamase gene, suggesting that this chromosomal enzyme is the progenitor of the CTX-M-2/5 cluster.

  10. RNA polymerase II interacts with the promoter region of the noninduced hsp70 gene in Drosophila melanogaster cells.

    Science.gov (United States)

    Gilmour, D S; Lis, J T

    1986-11-01

    By using a protein-DNA cross-linking method (D. S. Gilmour and J. T. Lis, Mol. Cell. Biol. 5:2009-2018, 1985), we examined the in vivo distribution of RNA polymerase II on the hsp70 heat shock gene in Drosophila melanogaster Schneider line 2 cells. In heat shock-induced cells, a high level of RNA polymerase II was detected on the entire gene, while in noninduced cells, the RNA polymerase II was confined to the 5' end of the hsp70 gene, predominantly between nucleotides -12 and +65 relative to the start of transcription. This association of RNA polymerase II was apparent whether the cross-linking was performed by a 10-min UV irradiation of chilled cells with mercury vapor lamps or by a 40-microsecond irradiation of cells with a high-energy xenon flash lamp. We hypothesize that RNA polymerase II has access to, and a high affinity for, the promoter region of this gene before induction, and this poised RNA polymerase II may be critical in the mechanism of transcription activation.

  11. Capacitive Proximity Sensor Has Longer Range

    Science.gov (United States)

    Vranish, John M.

    1992-01-01

    Capacitive proximity sensor on robot arm detects nearby object via capacitive effect of object on frequency of oscillator. Sensing element part of oscillator circuit operating at about 20 kHz. Total capacitance between sensing element and ground constitutes tuning capacitance of oscillator. Sensor circuit includes shield driven by replica of alternating voltage applied to sensing element. Driven shield concentrates sensing electrostatic field in exterior region to enhance sensitivity to object. Sensitivity and dynamic range has corresponding 12-to-1 improvement.

  12. Differential acetylation of histone H3 at the regulatory region of OsDREB1b promoter facilitates chromatin remodelling and transcription activation during cold stress.

    Directory of Open Access Journals (Sweden)

    Dipan Roy

    Full Text Available The rice ortholog of DREB1, OsDREB1b, is transcriptionally induced by cold stress and over-expression of OsDREB1b results in increase tolerance towards high salt and freezing stress. This spatio-temporal expression of OsDREB1b is preceded by the change in chromatin structure at the promoter and the upstream region for gene activation. The promoter and the upstream region of OsDREB1b genes appear to be arranged into a nucleosome array. Nucleosome mapping of ∼ 700 bp upstream region of OsDREB1b shows two positioned nucleosomes between -610 to -258 and a weakly positioned nucleosome at the core promoter and the TSS. Upon cold stress, there is a significant change in the nucleosome arrangement at the upstream region with increase in DNaseI hypersensitivity or MNase digestion in the vicinity of cis elements and TATA box at the core promoter. ChIP assays shows hyper-acetylation of histone H3K9 throughout the locus whereas region specific increase was observed in H3K14ac and H3K27ac. Moreover, there is an enrichment of RNA PolII occupancy at the promoter region during transcription activation. There is no significant change in the H3 occupancy in OsDREB1b locus negating the possibility of nucleosome loss during cold stress. Interestingly, cold induced enhanced transcript level of OsDREB1b as well as histone H3 acetylation at the upstream region was found to diminish when stressed plants were returned to normal temperature. The result indicates absolute necessity of changes in chromatin conformation for the transcription up-regulation of OsDREB1b gene in response to cold stress. The combined results show the existence of closed chromatin conformation at the upstream and promoter region of OsDREB1b in the transcription "off" state. During cold stress, changes in region specific histone modification marks promote the alteration of chromatin structure to facilitate the binding of transcription machinery for proper gene expression.

  13. Identification of the promoter region of human interleukin 1 type I receptor gene: multiple initiation sites, high G+C content, and constitutive expression.

    Science.gov (United States)

    Ye, K; Dinarello, C A; Clark, B D

    1993-01-01

    To better understand the role of interleukin 1 (IL-1) and its receptor in disease, we have isolated a genomic clone of the human IL-1 type I receptor and have identified the promoter region. There are multiple transcriptional initiation sites as demonstrated by primer extension. DNA sequence analysis shows that the promoter region contains neither a TATA nor a CAAT box; however, the 5' upstream regulatory elements contain two AP-1-like binding sites. The internal regulatory sequences found immediately downstream to the 5' transcriptional start site contain four Sp1 binding domains and have a high G+C content of 75%. This portion of the 5' untranslated region of the mRNA can form stable secondary structure as predicted by computer modeling. Base pairs -4 to + 10 share striking resemblance to an initiator sequence that directs basal expression of certain TATA-less genes-e.g., terminal deoxynucleotidyltransferase in lymphocytes. The IL-1 receptor promoter directs basal expression of chloramphenicol acetyltransferase in transiently transfected cells. Overall, the promoter of the IL-1 type I receptor gene resembles that of constitutively expressed genes that have housekeeping- and/or growth-related functions. The constitutive nature of the promoter may account for this gene being expressed at low levels in diverse cell types. Our finding sheds more understanding into the mechanisms governing the regulation of the IL-1 receptor in health and disease. Images Fig. 2 Fig. 6 PMID:8460136

  14. The Role of a CA Repeat Polymorphism in the Promoter Region of the Insulin like Growth Factor-I gene in Physiology and the Pathophysiology of Diabetes Mellitus

    NARCIS (Netherlands)

    I. Rietveld (Ingrid)

    2009-01-01

    textabstractA polymorphism in the promoter region of the IGF-I gene is amongst others related to total IGF-I serum levels, body height and type 2 diabetes. In this thesis, we investigated the influence of this polymorphism on the age-related decline, secular trend in body height, beta cell function,

  15. Association of human liver bilirubin UDP-glucuronyltransferase activity with a polymorphism in the promoter region of the UGT1A1 gene

    NARCIS (Netherlands)

    Raijmakers, MTM; Jansen, PLM; Steegers, EAP; Peters, WHM

    Background/Aims: Gilbert's syndrome is a benign form of a deficiency in bilirubin glucuronidation. It is associated with a homozygous polymorphism, A(TA)(7)TAA instead of A(TA)(6)TAA, in the TATA-box of the promoter region of the bilirubin UDP-glucuronyltransferase gene. In this study the

  16. Detection of a 640-bp deletion in the Aggregatibacter actinomycetemcomitans leukotoxin promoter region in isolates from an adolescent of Ethiopian origin

    Directory of Open Access Journals (Sweden)

    Rolf Claesson

    2015-04-01

    Full Text Available The expression of the leukotoxin of Aggregatibacter actinomycetemcomitans is regulated by the leukotoxin promoter. A 530-bp deletion or an 886-bp insertion sequence (IS element in this region has earlier been described in highly leukotoxic isolates. Here, we report on highly leukotoxic isolate with a 640-bp deletion, which was detected in an adolescent of Ethiopian origin.

  17. Serotonin Transporter Promoter Region (5-HTTLPR) Polymorphism Is Not Associated With Paroxetine-Induced Ejaculation Delay in Dutch Men With Lifelong Premature Ejaculation

    NARCIS (Netherlands)

    Janssen, Paddy K C; Zwinderman, Aeilko H; Olivier, Berend; Waldinger, Marcel D

    PURPOSE: To investigate the association between the 5-HT-transporter-gene-linked promoter region (5-HTTLPR) polymorphism and 20-mg paroxetine-induced ejaculation delay in men with lifelong premature ejaculation (LPE). MATERIALS AND METHODS: This was a prospective study of 10 weeks of paroxetine

  18. Genetic variants in promoters and coding regions of the muscle glycogen synthase and the insulin-responsive GLUT4 genes in NIDDM

    DEFF Research Database (Denmark)

    Bjørbaek, C; Echwald, Søren Morgenthaler; Hubricht, P

    1994-01-01

    regions and regions of importance for translation, as well as coding sequences of the two genes, were studied using single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. The genetic analyses were performed in subgroups of 52 Caucasian NIDDM patients and 25 age-matched healthy......To examine the hypothesis that variants in the regulatory or coding regions of the glycogen synthase (GS) and insulin-responsive glucose transporter (GLUT4) genes contribute to insulin-resistant glucose processing of muscle from non-insulin-dependent diabetes mellitus (NIDDM) patients, promoter......'-untranslated region, and the coding region of the GLUT4 gene showed four polymorphisms, all single nucleotide substitutions, positioned at -581, 1, 30, and 582. None of the three changes in the regulatory region of the gene had any major influence on expression of the GLUT4 gene in muscle. The variant at 582...

  19. Analysis of the Impact of the Flow of Migrant Workers on Regional Economy: Based on the Thought about the Promotion of Jiangxi Regional Economic Competitiveness

    National Research Council Canada - National Science Library

    Sun Yuping

    2016-01-01

    ... of “demographic dividend” is the non-agricultural migrant population, i.e., migrant workers. The transfer employment of migrant workers has typical regional liquidity, and the imbalance of regional economy causes the flow of many migrant workers...

  20. Dual Roles of the Hemagglutinin Segment-Specific Noncoding Nucleotides in the Extended Duplex Region of the Influenza A Virus RNA Promoter.

    Science.gov (United States)

    Wang, Jingfeng; Li, Jinghua; Zhao, Lili; Cao, Mengmeng; Deng, Tao

    2017-01-01

    We recently reported that the segment-specific noncoding regions (NCRs) of the hemagglutinin (HA) and neuraminidase (NA) segments are subtype specific, varying significantly in sequence and length at both the 3' and 5' ends. Interestingly, we found that nucleotides CC at positions 13 and 14 at the 3' end and GUG at positions 14 to 16 at the 5' end (termed 14' and 16' to distinguish them from 3' positions) are absolutely conserved among all HA subtype-specific NCRs. These HA segment-specific NCR nucleotides are located in the extended duplex region of the viral RNA promoter. In order to understand the significance of these highly conserved HA segment-specific NCR nucleotides in the virus life cycle, we performed extensive mutagenesis on the HA segment-specific NCR nucleotides and studied their functional significance in regulating influenza A virus replication in the context of the HA segment with both RNP reconstitution and virus infection systems. We found that the base pairing of the 3'-end 13 position with the 5'-end 14' position ((3')13-(5')14') position is critical for RNA promoter activity while the identity of the base pair is critical in determining HA segment packaging. Moreover, the identity of the residue at the 3'-end 14 position is functionally more important in regulating virus genome packaging than in regulating viral RNA synthesis. Taken together, these results demonstrated that the HA segment-specific NCR nucleotides in the extended duplex region of the promoter not only form part of the promoter but also play a key role in controlling virus selective genome packaging. The segment-specific complementary nucleotides (13 to 15 in the 3' end and 14' to 16' in the 5' end) in the extended duplex region of the influenza virus RNA promoter vary significantly among different segments and have rarely been studied. Here, we performed mutagenesis analysis of the highly conserved HA segment-specific nucleotides in the extended duplex region and examined their

  1. A novel -192c/g mutation in the proximal P2 promoter of the hepatocyte nuclear factor-4 alpha gene (HNF4A) associates with late-onset diabetes

    DEFF Research Database (Denmark)

    Ek, Jakob; Hansen, Sara P; Lajer, Maria

    2006-01-01

    Recently, it has been shown that mutations in the P2 promoter of the hepatocyte nuclear factor (HNF)-4 alpha gene (HNF4A) cause maturity-onset diabetes of the young (MODY), while single nucleotide polymorphisms in this locus are associated with type 2 diabetes. In this study, we examined 1,189 bp......,812 glucose-tolerant subjects for the -192c/g mutation and identified 5 diabetic and 1 glucose-tolerant mutation carriers (P=0.004). Examination of the families showed that carriers of the -192c/g mutation had a significantly impaired glucose-stimulated insulin release and lower levels of serum total...

  2. [A case of proximal type epithelioid sarcoma of the perineum].

    Science.gov (United States)

    Murashima, Takaya; Kamibeppu, Toyoharu; Hiromasa, Tukino; Mukai, Syoichiro; Kamoto, Toshiyuki

    2013-11-01

    Epithelioid sarcomas are rare soft tissue neoplasms which occur more often in young people. They tend to relapse, metastatize and show poor prognosis. Proximal-type epithelioid sarcomas arise from the more proximal part of body and are more malignant than distal-type epithelioid sarcomas. We present a case of proximal-type epithelioid sarcoma which occurred in the perineum. A 24-year-old male visited our hospital with the chief complaint of pain in the perineum. Computed tomography and magnetic resonance imaging showed a tumor 30×23×17 mm in diameter in the perineal region. The tumor was excised regionally and the pathological examination with immunohistochemical staining revealed that the tumor was proximal-type epithelioid sarcoma. The patient is free of recurrence and metastasis one year after local excision.

  3. Comparative analyses of bidirectional promoters in vertebrates

    Directory of Open Access Journals (Sweden)

    Taylor James

    2008-05-01

    Full Text Available Abstract Background Orthologous genes with deep phylogenetic histories are likely to retain similar regulatory features. In this report we utilize orthology assignments for pairs of genes co-regulated by bidirectional promoters to map the ancestral history of the promoter regions. Results Our mapping of bidirectional promoters from humans to fish shows that many such promoters emerged after the divergence of chickens and fish. Furthermore, annotations of promoters in deep phylogenies enable detection of missing data or assembly problems present in higher vertebrates. The functional importance of bidirectional promoters is indicated by selective pressure to maintain the arrangement of genes regulated by the promoter over long evolutionary time spans. Characteristics unique to bidirectional promoters are further elucidated using a technique for unsupervised classification, known as ESPERR. Conclusion Results of these analyses will aid in our understanding of the evolution of bidirectional promoters, including whether the regulation of two genes evolved as a consequence of their proximity or if function dictated their co-regulation.

  4. Zebrafish U6 small nuclear RNA gene promoters contain a SPH element in an unusual location.

    Science.gov (United States)

    Halbig, Kari M; Lekven, Arne C; Kunkel, Gary R

    2008-09-15

    Promoters for vertebrate small nuclear RNA (snRNA) genes contain a relatively simple array of transcriptional control elements, divided into proximal and distal regions. Most of these genes are transcribed by RNA polymerase II (e.g., U1, U2), whereas the U6 gene is transcribed by RNA polymerase III. Previously identified vertebrate U6 snRNA gene promoters consist of a proximal sequence element (PSE) and TATA element in the proximal region, plus a distal region with octamer (OCT) and SphI postoctamer homology (SPH) elements. We have found that zebrafish U6 snRNA promoters contain the SPH element in a novel proximal position immediately upstream of the TATA element. The zebrafish SPH element is recognized by SPH-binding factor/selenocysteine tRNA gene transcription activating factor/zinc finger protein 143 (SBF/Staf/ZNF143) in vitro. Furthermore, a zebrafish U6 promoter with a defective SPH element is inefficiently transcribed when injected into embryos.

  5. The fiber specificity of the cotton FSltp4 gene promoter is regulated by an AT-rich promoter region and the AT-hook transcription factor GhAT1.

    Science.gov (United States)

    Delaney, Sven K; Orford, Sharon J; Martin-Harris, Michael; Timmis, Jeremy N

    2007-10-01

    Fiber-specific genes are expressed preferentially or exclusively in cotton (Gossypium spp.) fiber and are thought to have important functions in fiber development. The promoters of these genes are of interest because they control transcription in the fiber cell and may be used in the genetic manipulation of fiber quality. The promoter of a cotton lipid transfer protein gene, FSltp4, was isolated and shown to direct fiber-specific transcription of an abundant mRNA in cotton. In transgenic tobacco, this promoter was strongly active in leaf trichomes. Deletion analysis of the promoter identified an AT-rich 84 bp fiber specificity region (FSR) necessary for activity exclusively in the fiber cells. Cotton fiber proteins that bind the FSR were isolated using a yeast one-hybrid assay. One of these was a putative AT-hook transcription factor (GhAT1) containing two AT-hook motifs. GhAT1 was shown to be nuclear localized, and GhAT1 transcripts were found to be preferentially expressed in ovules and non-fiber tissues. Overexpression of GhAT1 strongly repressed the activity of the FSltp4 promoter in the trichomes of transgenic tobacco. These results suggest that GhAT1 assists in the specification of fiber cells by repressing FSltp4 in the non-fiber tissues of the cotton plant.

  6. Developing survey metrics for analysing cross-border proximity

    DEFF Research Database (Denmark)

    Makkonen, Teemu; Williams, Allan

    2017-01-01

    Cross-border innovation cooperation (CBIC) has been heralded as one of the corner stones of innovation-driven growth opportunities for firms located in cross-border regions (CBRs). The success of this cooperation is affected by varying types of proximities identified in the literature....... The findings indicate that the developed survey metrics are effective in depicting the phenomenon of proximity. The foundational work undertaken in this research note provides a platform, and catalyst, for more extensive investigations of the topic....

  7. Fractures of the proximal humerus

    DEFF Research Database (Denmark)

    Brorson, Stig

    2013-01-01

    . The bandages were further supported by splints made of wood or coarse grass. Healing was expected in forty days. Different fracture patterns have been discussed and classified since Ancient Greece. Current classification of proximal humeral fractures mainly relies on the classifications proposed by Charles......, classification of proximal humeral fractures remains a challenge for the conduct, reporting, and interpretation of clinical trials. The evidence for the benefits of surgery in complex fractures of the proximal humerus is weak. In three systematic reviews I studied the outcome after locking plate osteosynthesis......Fractures of the proximal humerus have been diagnosed and managed since the earliest known surgical texts. For more than four millennia the preferred treatment was forceful traction, closed reduction, and immobilization with linen soaked in combinations of oil, honey, alum, wine, or cerate...

  8. TSA-induced DNMT1 down-regulation represses hTERT expression via recruiting CTCF into demethylated core promoter region of hTERT in HCT116.

    Science.gov (United States)

    Choi, Jee-Hye; Min, Na Young; Park, Jina; Kim, Jin Hong; Park, Soo Hyun; Ko, Young Jong; Kang, Yoonsung; Moon, Young Joon; Rhee, Sangmyung; Ham, Seung Wook; Park, Ae Ja; Lee, Kwang-Ho

    2010-01-01

    Trichostatin A (TSA), an inhibitor of histone deacetylase, is a well-known antitumor agent that effectively and selectively induces tumor growth arrest and apoptosis. Recently, it was reported that hTERT is one of the primary targets for TSA-induced apoptosis in cancer cells but the mechanism of which has not yet been elucidated. In the present study, to better understand the epigenetic regulation mechanism responsible for the repression of hTERT by TSA, we examined expression of hTERT in the HCT116 colon cancer cell line after treatment with TSA and performed site-specific CpG methylation analysis of the hTERT promoter. We found that TSA-induced the demethylation of site-specific CpGs on the promoter of hTERT, which was caused by down-regulation of DNA methyltransferase 1 (DNMT1). Among the demethylated region, the 31st-33rd CpGs contained a binding site for CTCF, an inhibitor of hTERT transcription. ChIP analysis revealed that TSA-induced demethylation of the 31st-33rd CpGs promoted CTCF binding on hTERT promoter, leading to repression of hTERT. Taken together, down-regulation of DNMT1 by TSA caused demethylation of a CTCF binding site on the hTERT promoter, the result of which was repression of hTERT via recruitment of CTCF to the promoter. Copyright 2009 Elsevier Inc. All rights reserved.

  9. Conserved POU/OCT- and GATA-binding sites in 5'-flanking promoter region of mammalian WNT8B orthologs.

    Science.gov (United States)

    Katoh, Masuko; Katoh, Masaru

    2007-05-01

    WNT family members are secreted-type glycoproteins regulating cell fate, planar cell polarity, cell adhesion, and cell movement. WNT signals are context-dependently transduced to the canonical pathway for the transcriptional up-regulation of MYC, CCND1, FGF20, JAG1, WISP1 and DKK1 genes, and also to the non-canonical pathway for the activation of RHOA, JNK, PKC, NFAT and NLK signaling cascades. We cloned and characterized the wild-type human WNT8B, while another group the aberrant human WNT8B with Gly230Ala and Arg284Leu amino-acid substitutions. Although WNT8B is undetectable in normal adult tissues by using Northern blot analyses, WNT8B is expressed in gastric cancer, pancreatic cancer, colorectal cancer, breast cancer, and embryonal tumors. Here, comparative integromics on WNT8B orthologs were investigated by using bioinformatics (Techint) and human intelligence (Humint). Cow Wnt8b gene was identified within NW_001494361.1 genome sequence. Predicted sequence XM_582222.3 was an artificial cow Wnt8b with aberrant prediction for the first exon. Cow Wnt8b complete coding sequence was found to encode a 350-amino-acid protein, which showed 96.9% total-amino-acid identity with human WNT8B. Comparative proteomics revealed that N-terminal signal peptide, 22 Cys residues, two Asn-linked glycosylation sites, Gly230, and Arg284 of human WNT8B were conserved among mammalian WNT8B orthologs. Comparative genomics revealed that POU/OCT- and GATA-binding sites in the 5'-flanking promoter region were conserved among human, chimpanzee, cow, mouse, and rat WNT8B orthologs. In silico expression analyses revealed that human WNT8B was expressed in embryoid body derived from embryonic stem (ES) cells, hepatocyte progenitors derived from ES cells, fetal brain, diffuse-type gastric cancer, colorectal cancer, prostate cancer, and ovarian fibrotheoma. Based on the expression profiles of POU and GATA family transcription factors, it was revealed that WNT8B expression in hepatocyte

  10. Variability in the precore and core promoter regions of HBV strains in Morocco: characterization and impact on liver disease progression.

    Directory of Open Access Journals (Sweden)

    Bouchra Kitab

    Full Text Available BACKGROUND: Hepatitis B virus (HBV is one of the most common human pathogens that cause aggressive hepatitis and advanced liver disease (AdLD, including liver cirrhosis and Hepatocellular Carcinoma. The persistence of active HBV replication and liver damage after the loss of hepatitis B e antigen (HBeAg has been frequently associated with mutations in the pre-core (pre-C and core promoter (CP regions of HBV genome that abolish or reduce HBeAg expression. The purpose of this study was to assess the prevalence of pre-C and CP mutations and their impact on the subsequent course of liver disease in Morocco. METHODS/PRINCIPAL FINDINGS: A cohort of 186 patients with HBeAg-negative chronic HBV infection was studied (81 inactive carriers, 69 with active chronic hepatitis, 36 with AdLD. Pre-C and CP mutations were analyzed by PCR-direct sequencing method. The pre-C stop codon G1896A mutation was the most frequent (83.9% and was associated with a lower risk of AdLD development (OR, 0.4; 95% CI, 0.15-1.04; p = 0.04. HBV-DNA levels in patients with G1896A were not significantly different from the other patients carrying wild-type strains (p = 0.84. CP mutations C1653T, T1753V, A1762T/G1764A, and C1766T/T1768A were associated with higher HBV-DNA level and increased liver disease severity. Multiple logistic regression analysis showed that older age (≥ 40 years, male sex, high viral load (>4.3 log(10 IU/mL and CP mutations C1653T, T1753V, A1762T/G1764A, and C1766T/T1768A were independent risk factors for AdLD development. Combination of these mutations was significantly associated with AdLD (OR, 7.52; 95% CI, 4.8-8; p<0.0001. CONCLUSIONS: This study shows for the first time the association of HBV viral load and CP mutations with the severity of liver disease in Moroccan HBV chronic carriers. The examination of CP mutations alone or in combination could be helpful for prediction of the clinical outcome.

  11. IκBα polymorphism at promoter region (rs2233408 influences the susceptibility of gastric cancer in Chinese

    Directory of Open Access Journals (Sweden)

    Sung Joseph JY

    2010-02-01

    Full Text Available Abstract Background Nuclear factor of kappa B inhibitor alpha (IκBα protein is implicated in regulating a variety of cellular process from inflammation to tumorigenesis. The objective of this study was to investigate the susceptibility of rs2233408 T/C genotype in the promoter region of IκBα to gastric cancer and the association of this polymorphism with clinicopathologic variables in gastric cancer patients. Methods A population-based case-control study was conducted between 1999 and 2006 in Guangdong Province, China. A total of 564 gastric cancer patients and 566 healthy controls were enrolled in this study. rs2233408 genotypes in IκBα were analyzed by TaqMan SNP genotyping assay. Results Both rs2233408 T homozygote (TT and T heterozygotes (TC and TT had significantly reduced gastric cancer risk (TT: OR = 0.250, 95% CI = 0.069-0.909, P = 0.035; TC and TT: OR = 0.721, 95% CI = 0.530-0.981, P = 0.037, compared with rs2233408 C homozygote (CC. rs2233408 T heterozygotes were significantly associated with reduced risk of intestinal-type gastric cancer with ORs of 0.648 (95% CI = 0.459-0.916, P = 0.014, but not with the diffuse or mix type of gastric cancer. The association between rs2233408 T heterozygotes and gastric cancer appeared more apparent in the older patients (age>40 (OR = 0.674, 95% CI = 0.484-0.939, P = 0.02. rs2233408 T heterozygotes was associated with non-cardiac gastric cancer (OR = 0.594, 95% CI = 0.411-0.859, P = 0.006, but not with cardiac gastric cancer. However, rs2233408 polymorphism was not associated with the prognosis of gastric cancer patients. Conclusions IκBα rs2233408 T heterozygotes were associated with reduced risk of gastric cancer, especially for the development of certain subtypes of gastric cancer in Chinese population.

  12. The infrastructure of psychological proximity

    DEFF Research Database (Denmark)

    Nickelsen, Niels Christian Mossfeldt

    2015-01-01

    ). The experience of psychological proximity between patient and nurse is provided through confidence, continuity and the practical set-up. This constitutes an important enactment of skillfulness, which may render telemedicine a convincing health service in the future. Methodology: The study draws on a pilot...... (Langstrup & Winthereik 2008). This study contributes by showing the infrastructure of psychological proximity, which is provided by way of device, confidence, continuity and accountability....

  13. The use of amplified flanking region-PCR in the isolation of laccase promoter sequences from the edible fungus Pleurotus sajor-caju.

    Science.gov (United States)

    Soden, D M; Dobson, A D W

    2003-01-01

    To determine the regulation of laccase isozyme gene transcription in Pleurotus sajor-caju in response to different aromatic inducers and physiological parameters. The promoter regions for each of four different laccase isozymes were cloned from P. sajor-caju, using amplified flanking region-PCR (AFR-PCR). Sequences stretching 724, 214, 840 and 1740 bp upstream from the predicted start codons for lac1, lac2, lac3 and lac4, respectively, were cloned in each case and analysed for the presence of putative transcriptional response elements. A number of putative response elements including metal response elements, xenobiotic response elements and antioxidant response elements appear to be present. In addition putative consensus sequences such as those for the binding of AP1, AP2, creA and NIT2 transcription factors, which are involved in nitrogen and carbon regulation in different fungi, are also present in the promoter regions of some of the isozymes. These elements may be involved in the transcriptional regulation of laccase gene expression in P. sajor-caju. The presence of a number of putative transcriptional response elements in the promoter regions of different isozyme genes indicates a potential role for these sites in regulating laccase gene transcription in P. sajor-caju. In addition this work demonstrates the potential usefulness of AFR-PCR as a technique to clone fungal DNA sequences located upstream from known sequences.

  14. miR-2478 inhibits TGFβ1 expression by targeting the transcriptional activation region downstream of the TGFβ1 promoter in dairy goats.

    Science.gov (United States)

    Li, Zhuanjian; Lan, Xianyong; Han, Ruili; Wang, Jing; Huang, Yongzhen; Sun, Jiajie; Guo, Wenjiao; Chen, Hong

    2017-02-15

    In a previous study, miR-2478 was demonstrated to be up-regulated in dairy goat mammary glands during peak lactation compared with the dry period. However, the detailed mechanisms by which miR-2478 regulates physiological lactation and mammary gland development in dairy goats remain unclear. In this study, we used bioinformatics analysis and homologous cloning to predict the target genes of miR-2478 and selected INSR, FBXO11, TGFβ1 and ING4 as candidate target genes of miR-2478. Subsequently, by targeting the 5'UTR of the TGFβ1 gene, we verified that miR-2478 significantly inhibited TGFβ1 transcription and the Pearson's correlation coefficient between miR-2478 expression and TGFβ1 expression was -0.98. Furthermore, we identified the potential promoter and transcription factor binding regions of TGFβ1 and analyzed the potential mechanisms of interaction between miR-2478 and TGFβ1. Dual-luciferase reporter assays revealed that two regions, spanning from -904 to -690 bp and from -79 to +197 bp, were transcription factor binding regions of TGFβ1. Interesting, the miR-2478 binding sequence was determined to span from +123 to +142 bp in the TGFβ1 gene promoter. Thus, our results have demonstrated that miR-2478 binds to the core region of the TGFβ1 promoter and that it affects goat mammary gland development by inhibiting TGFβ1 transcription.

  15. Functional characterization of the promoter region of the human EVI1 gene in acute myeloid leukemia: RUNX1 and ELK1 directly regulate its transcription.

    Science.gov (United States)

    Maicas, M; Vázquez, I; Vicente, C; García-Sánchez, M A; Marcotegui, N; Urquiza, L; Calasanz, M J; Odero, M D

    2013-04-18

    The EVI1 gene (3q26) codes for a transcription factor with important roles in normal hematopoiesis and leukemogenesis. High expression of EVI1 is a negative prognostic indicator of survival in acute myeloid leukemia (AML) irrespective of the presence of 3q26 rearrangements. However, the only known mechanisms that lead to EVI1 overexpression are 3q aberrations, and the MLL-ENL oncoprotein, which activates the transcription of EVI1 in hematopoietic stem cells. Our aim was to characterize the functional promoter region of EVI1, and to identify transcription factors involved in the regulation of this gene. Generation of seven truncated constructs and luciferase reporter assays allowed us to determine a 318-bp region as the minimal promoter region of EVI1. Site-directed mutagenesis and chromatin immunoprecipitation (ChIP) assays identified RUNX1 and ELK1 as putative transcription factors of EVI1. Furthermore, knockdown of RUNX1 and ELK1 led to EVI1 downregulation, and their overexpression to upregulation of EVI1. Interestingly, in a series of patient samples with AML at diagnosis, we found a significant positive correlation between EVI1 and RUNX1 at protein level. Moreover, we identified one of the roles of RUNX1 in the activation of EVI1 during megakaryocytic differentiation. EVI1 knockdown significantly inhibited the expression of megakaryocytic markers after treating K562 cells with TPA, as happens when knocking down RUNX1. In conclusion, we define the minimal promoter region of EVI1 and demonstrate that RUNX1 and ELK1, two proteins with essential functions in hematopoiesis, regulate EVI1 in AML. Furthermore, our results show that one of the mechanisms by which RUNX1 regulates the transcription of EVI1 is by acetylation of the histone H3 on its promoter region. This study opens new directions to further understand the mechanisms of EVI1 overexpressing leukemias.

  16. Renal proximal tubule angiotensin AT1A receptors regulate blood pressure

    OpenAIRE

    Li, Huiping; Weatherford, Eric T.; Davis, Deborah R.; Keen, Henry L.; Grobe, Justin L.; Daugherty, Alan; Cassis, Lisa A.; Allen, Andrew M.; Sigmund, Curt D.

    2011-01-01

    All components of the renin angiotensin system necessary for ANG II generation and action have been reported to be present in renal proximal convoluted tubules. Given the close relationship between renal sodium handling and blood pressure regulation, we hypothesized that modulating the action of ANG II specifically in the renal proximal tubules would alter the chronic level of blood pressure. To test this, we used a proximal tubule-specific, androgen-dependent, promoter construct (KAP2) to ge...

  17. The first year experience of occupational therapy students at an Australian regional university: Promoting student retention and developing a regional and remote workforce.

    Science.gov (United States)

    Boehm, Jackie; Cordier, Reinie; Thomas, Yvonne; Tanner, Bronwyn; Salata, Karen

    2017-02-01

    Student retention at regional universities is important in addressing regional and remote workforce shortages. Students attending regional universities are more likely to work in regional areas. First year experience at university plays a key role in student retention. This study aimed to explore factors influencing the first year experience of occupational therapy students at a regional Australian university. Surveys were administered to 58 second year occupational therapy students in the first week of second year. Data were analysed using descriptive statistics, inferential statistics (Pearson χ2 ; Spearman rho) and summarising descriptive responses. An Australian regional university. Second year undergraduate occupational therapy students. Factors influencing students' decisions to study and continue studying occupational therapy; factors enhancing first year experience of university. Fifty-four students completed the survey (93.1%). A quarter (25.9%) of students considered leaving the course during the first year. The primary influence for continuing was the teaching and learning experience. Most valued supports were orientation week (36.7%) and the first year coordinator (36.7%). The importance of the first year experience in retaining occupational therapy students is highlighted. Engagement with other students and staff and academic support are important factors in facilitating student retention. It is important to understand the unique factors influencing students' decisions, particularly those from regional and remote areas, to enter and continue in tertiary education to assist in implementing supports and strategies to improve student retention. © 2015 National Rural Health Alliance Inc.

  18. The influence of metabolic syndrome, physical activity and genotype on catechol-O-methyl transferase promoter-region methylation in schizophrenia.

    Science.gov (United States)

    Lott, S A; Burghardt, P R; Burghardt, K J; Bly, M J; Grove, T B; Ellingrod, V L

    2013-06-01

    The catechol-O-methyl transferase (COMT) 158Val/Met variant has been suggested to play a role in COMT function. Epigenetic regulation of COMT may further influence the prevalence of metabolic syndrome in these patient populations. This study examined the correlation between COMT promoter methylation and metabolic syndrome in schizophrenia patients receiving atypical antipsychotic (AAP) therapy. DNA was extracted from peripheral blood samples of schizophrenia subjects screened for metabolic syndrome. Pyrosequencing was used to analyze two methylation sites of the soluble COMT (COMT-s) promoter region. Associations between AAP use, lifestyle variables, metabolic syndrome and COMT genotype with peak methylation values were analyzed. Data are reported in 85 subjects. Methylation on CpG site 1 had a mean of 79.08% (±4.71) and it was 12.43% (±1.19) on site 2. COMT genotype proved to be an indicator of COMT methylation status on site 1 (F(2, 84)=5.78, P=0.0044) and site 2 (F(2, 84),=3.79, P=0.027). A significant negative correlation between physical activity and COMT promoter region methylation was found in Val/Val homozygous patients (site 1: P=0.013 and site 2: P=0.019). Those homozygous for Met/Met showed a positive correlation between promoter site methylation and physical activity (site 1: P=0.027, site 2: P=0.005), and between CpG site methylation and metabolic syndrome (site 1: P=0.002; site 2: P=0.001). The results of this study suggest that COMT promoter region methylation is largely influenced by COMT genotype and that physical activity plays a significant role in epigenetic modulation of COMT.

  19. Effect of electroacupuncture at distal–proximal acupoint combinations on spinal interleukin-1 beta in a rat model of neuropathic pain

    Directory of Open Access Journals (Sweden)

    Huili Jiang

    2015-01-01

    Conclusion: EA at distal + proximal acupoints, distal points, as well as proximal points attenuated upregulation of spinal IL-1β, alleviated the extent of neuropathic pain hypersensitivity, and promoted mechanical withdrawal threshold, resulting in EA analgesia.

  20. Promoter-region hypermethylation and expression downregulation of Yy1 (Yin yang 1) in preneoplastic liver lesions in a thioacetamide rat hepatocarcinogenesis model

    Energy Technology Data Exchange (ETDEWEB)

    Abe, Hajime [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193 (Japan); Ogawa, Takashi; Wang, Liyun [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Kimura, Masayuki; Tanaka, Takeshi; Morita, Reiko [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193 (Japan); Yoshida, Toshinori [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Shibutani, Makoto, E-mail: mshibuta@cc.tuat.ac.jp [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan)

    2014-11-01

    Thioacetamide (TAA) has been used to develop a rodent model for hepatocarcinogenesis. To determine the genes with epigenetic modifications in early hepatocarcinogenesis, we did a genome-wide scan for hypermethylated promoter regions using CpG island microarrays in TAA-promoted rat liver tissue. Eight genes were selected based on the microarray profile; of these, Yy1 and Wdr45b were confirmed to be hypermethylated by methylation-specific polymerase chain reaction (PCR) and pyrosequencing and downregulated by real-time reverse transcription PCR. Non-neoplastic liver cells had nuclear Yy1 immunoreactivity, while preneoplastic foci with glutathione S-transferase placental form (GST-P) immunoreactivity had decreased Yy1 immunoreactivity. The incidence of these foci was proportional to the dose of TAA administered. Co-expression analysis of gene products downstream of Yy1 revealed increased nuclear phospho-c-Myc{sup +} foci as well as nuclear and cytoplasmic p21{sup Cip1+} foci in Yy1{sup −} or GST-P{sup +} foci in response to TAA-promotion dose. Although the absolute number of cells was low, the incidence of death receptor 5{sup −} foci was increased in Yy1{sup −} foci in proportion to the TAA dose. Yy1{sup −}/GST-P{sup +} foci revealed a higher number of proliferating cell nuclear antigen (PCNA)-immunoreactive cells than Yy1{sup +}/GST-P{sup +} foci, while cleaved caspase-3{sup +} cells were unchanged between Yy1{sup –}/GST-P{sup +} and Yy1{sup +}/GST-P{sup +} foci. In the case of Wdr45b, most GST-P{sup +} foci were Wdr45b{sup –} and were not increased by TAA promotion. These results suggest involvement of Yy1 in the epigenetic gene regulation at the early stages of TAA promoted cell proliferation and concomitant cell cycle arrest in preneoplastic lesions. - Highlights: • Epigenetically downregulated genes were searched in TAA-promnoted rat livers. • Yy1 and Wdr45b showed promoter-region hypermethylation and mRNA downregulation. • TAA promoted

  1. Cross-border regional innovation systems

    DEFF Research Database (Denmark)

    Makkonen, Teemu; Rohde, Stephan

    2016-01-01

    The concept of cross-border regional innovation systems (CBRIS) surfaced in the literature on economic geography through discourses that highlighted the need of broadening innovation systems to cross-border contexts. Since these early discussions, the theoretical backgrounds of CBRIS have been...... elaborated through notions of geographical scale, proximity and related variety in a range of conceptual papers proposing CBRIS as a comprehensive framework for analysing regional cross-border integration. However, the empirical literature on CBRIS has failed to keep up with the advances in conceptualisation...... of understanding how suggested policy measures based on CBRIS reasoning have been implemented in border regions, and their effectiveness in promoting cross-border integration....

  2. Transverse Stress Fracture of the Proximal Patella

    Science.gov (United States)

    Atsumi, Satoru; Arai, Yuji; Kato, Ko; Nishimura, Akinobu; Nakazora, Shigeto; Nakagawa, Shuji; Ikoma, Kazuya; Fujiwara, Hiroyoshi; Sudo, Akihiro; Kubo, Toshikazu

    2016-01-01

    Abstract Among stress fractures associated with sports activities, patellar stress fracture is rare. Regarding patella stress fractures, so far only distal transverse or lateral longitudinal fractures have been reported, but there are no reports of transverse fractures occurring in the proximal patella. We describe an extremely rare case of transverse stress fracture of proximal patella in a 9-year-old athlete. A 9-year old boy, who participated in sports (sprints and Kendo) presented with left knee pain without any external injury. In plain radiographs, a fracture line was observed in the proximal 1/3 of the left patella, and a patella stress fracture was diagnosed. For treatment, because 7 months of conservative therapy showed no improvement, internal fixation was carried out using Acutrak screws, and bone union was thus achieved. Three months after the operation, he was able to return to his previous level of athletic sports activity. Regarding the mechanism of onset, it is believed that the causes are longitudinal traction force and patellofemoral contact pressure. On the other hand, the contact region of the patella with the femur changes with the flexion angle of the knee. In the current case, the fracture occurred at a site where the patella was in contact with the femur at a flexion angle of >90°, so it is believed that it occurred as a clinical condition from being subjected to repeated longitudinal traction force and patellofemoral contact pressure at a flexion angle of >90°, during the sports activities of sprints and Kendo. The nonunion of the transverse stress fracture of his proximal patella was successfully treated with internal fixation using Acutrak screws. PMID:26871789

  3. Sigma factor selectivity in Borrelia burgdorferi: RpoS recognition of the ospE/ospF/elp promoters is dependent on the sequence of the -10 region.

    Science.gov (United States)

    Eggers, Christian H; Caimano, Melissa J; Radolf, Justin D

    2006-03-01

    Members of the ospE/ospF/elp lipoprotein gene families of Borrelia burgdorferi, the Lyme disease agent, are transcriptionally upregulated in response to the influx of blood into the midgut of an infected tick. We recently have demonstrated that despite the high degree of similarity between the promoters of the ospF (P(ospF)) and ospE (P(ospE)) genes of B. burgdorferi strain 297, the differential expression of ospF is RpoS-dependent, while ospE is controlled by sigma(70). Herein we used wild-type and RpoS-deficient strains of B. burgdorferi and Escherichia coli to analyse transcriptional reporters consisting of a green fluorescent protein (gfp) gene fused to P(ospF), P(ospE), or two hybrid promoters in which the -10 regions of P(ospF) and P(ospE) were switched [P(ospF ) ((E - 10)) and P(ospE) ((F - 10)) respectively]. We found that the P(ospF)-10 region is both necessary and sufficient for RpoS-dependent recognition in B. burgdorferi, while sigma(70) specificity for P(ospE) is dependent on elements outside of the -10 region. In E. coli, sigma factor selectivity for these promoters was much more permissive, with expression of each being primarily due to sigma(70). Alignment of the sequences upstream of each of the ospE/ospF/elp genes from B. burgdorferi strains 297 and B31 revealed that two B31 ospF paralogues [erpK (BBM38) and erpL (BBO39)] have -10 regions virtually identical to that of P(ospF). Correspondingly, expression of gfp reporters based on the erpK and erpL promoters was RpoS-dependent. Thus, the sequence of the P(ospF)-10 region appears to serve as a motif for RpoS recognition, the first described for any B. burgdorferi promoter. Taken together, our data support the notion that B. burgdorferi utilizes sequence differences at the -10 region as one mechanism for maintaining the transcriptional integrity of RpoS-dependent and -independent genes activated at the onset of tick feeding.

  4. The sooner, the better: exercise outcome proximity and intrinsic motivation.

    Science.gov (United States)

    Evans, M Blair; Cooke, Lisa M; Murray, Robyn A; Wilson, Anne E

    2014-11-01

    Despite evidence that outcomes are highly valued when they are expected sooner rather than further into the future (Ainslie, 1975), limited research effort has been devoted to understanding the role of exercise outcome proximity. The purpose of this study was to examine how temporal proximity to positive outcomes influences exercisers' intrinsic motivation. We expected that focusing people on temporally proximal exercise outcomes would increase intrinsic motivation, especially among low-frequency exercisers. This online experimental study was completed by 135 community exercisers (Mage  = 31.11, SD = 10.29; 62% female) who reported an average of 4.86 exercise bouts per week (SD = 2.12). Participants were randomly assigned to a condition that primed temporally proximal positive exercise outcomes (i.e. experienced during or directly following an exercise bout) or temporally distal outcomes (i.e. experienced after days, months, or years of regular exercise). Participants then reported perceptions of behavioral regulation in exercise. As expected, the proximal exercise outcome condition elicited increased intrinsic regulation among those participants who exercised less frequently (i.e. 1 SD below the mean). This study reveals the importance of considering proximity as an important dimension of exercise outcomes-particularly when promoting intrinsic motivation among relatively infrequent exercisers. © 2014 The International Association of Applied Psychology.

  5. Proximal iliotibial band syndrome: case report

    Directory of Open Access Journals (Sweden)

    Guilherme Guadagnini Falotico

    2013-08-01

    Full Text Available OBJECTIVE: The overuse injuries in the hip joint occur commonly in sports practitioners and currently due to technical advances in diagnostic imaging, especially magnetic resonance imaging (MRI, are often misdiagnosed. Recently, a group of people were reported, all female, with pain and swelling in the pelvic region.T2-weighted MRI showed increased signal in the enthesis of the iliotibial band (ITB along the lower border of the iliac tubercle. We report a case of a 34 year old woman, non-professional runner, with pain at the iliac crest with no history of trauma and whose MRI was compatible with the proximal iliotibial band syndrome.

  6. Genome-wide Anaplasma phagocytophilum AnkA-DNA interactions are enriched in intergenic regions and gene promoters and correlate with infection-induced differential gene expression.

    Directory of Open Access Journals (Sweden)

    J Stephen Dumler

    2016-09-01

    Full Text Available Anaplasma phagocytophilum, an obligate intracellular prokaryote, infects neutrophils and alters cardinal functions via reprogrammed transcription. Large contiguous regions of neutrophil chromosomes are differentially expressed during infection. Secreted A. phagocytophilum effector AnkA transits into the neutrophil or granulocyte nucleus to complex with DNA in heterochromatin across all chromosomes. AnkA binds to gene promoters to dampen cis-transcription and also has features of matrix attachment region (MAR-binding proteins that regulate three-dimensional chromatin architecture and coordinate transcriptional programs encoded in topologically-associated chromatin domains. We hypothesize that identification of additional AnkA binding sites will better delineate how A. phagocytophilum infection results in reprogramming of the neutrophil genome. Using AnkA-binding ChIP-seq, we showed that AnkA binds broadly throughout all chromosomes in a reproducible pattern, especially at: i intergenic regions predicted to be matrix attachment regions (MARs; ii within predicted lamina-associated domains; and iii at promoters ≤3,000 bp upstream of transcriptional start sites. These findings provide genome-wide support for AnkA as a regulator of cis-gene transcription. Moreover, the dominant mark of AnkA in distal intergenic regions known to be AT-enriched, coupled with frequent enrichment in the nuclear lamina, provides strong support for its role as a MAR-binding protein and genome re-organizer. AnkA must be considered a prime candidate to promote neutrophil reprogramming and subsequent functional changes that belie improved microbial fitness and pathogenicity.

  7. DNA methylation of specific CpG sites in the promoter region regulates the transcription of the mouse oxytocin receptor.

    Directory of Open Access Journals (Sweden)

    Shimrat Mamrut

    Full Text Available Oxytocin is a peptide hormone, well known for its role in labor and suckling, and most recently for its involvement in mammalian social behavior. All central and peripheral actions of oxytocin are mediated through the oxytocin receptor, which is the product of a single gene. Transcription of the oxytocin receptor is subject to regulation by gonadal steroid hormones, and is profoundly elevated in the uterus and mammary glands during parturition. DNA methylation is a major epigenetic mechanism that regulates gene transcription, and has been linked to reduced expression of the oxytocin receptor in individuals with autism. Here, we hypothesized that transcription of the mouse oxytocin receptor is regulated by DNA methylation of specific sites in its promoter, in a tissue-specific manner. Hypothalamus-derived GT1-7, and mammary-derived 4T1 murine cell lines displayed negative correlations between oxytocin receptor transcription and methylation of the gene promoter, and demethylation caused a significant enhancement of oxytocin receptor transcription in 4T1 cells. Using a reporter gene assay, we showed that methylation of specific sites in the gene promoter, including an estrogen response element, significantly inhibits transcription. Furthermore, methylation of the oxytocin receptor promoter was found to be differentially correlated with oxytocin receptor expression in mammary glands and the uterus of virgin and post-partum mice, suggesting that it plays a distinct role in oxytocin receptor transcription among tissues and under different physiological conditions. Together, these results support the hypothesis that the expression of the mouse oxytocin receptor gene is epigenetically regulated by DNA methylation of its promoter.

  8. Tumour specific promoter region methylation of the human homologue of the Drosophila Roundabout gene DUTT1 (ROBO1) in human cancers.

    Science.gov (United States)

    Dallol, Ashraf; Forgacs, Eva; Martinez, Alonso; Sekido, Yoshitaka; Walker, Rosemary; Kishida, Takeshi; Rabbitts, Pamela; Maher, Eamonn R; Minna, John D; Latif, Farida

    2002-05-02

    The human homologue of the Drosophila Roundabout gene DUTT1 (Deleted in U Twenty Twenty) or ROBO1 (Locus Link ID 6091), a member of the NCAM family of receptors, was recently cloned from the lung cancer tumour suppressor gene region 2 (LCTSGR2 or U2020 region) at 3p12. DUTT1 maps within a region of overlapping homozygous deletions characterized in both small cell lung cancer lines (SCLC) and in a breast cancer line. In this report we (a) defined the genomic organization of the DUTT1 gene, (b) performed mutation and expression analysis of DUTT1 in lung, breast and kidney cancers, (c) identified tumour specific promoter region methylation of DUTT1 in human cancers. The gene was found to contain 29 exons and spans at least 240 kb of genomic sequence. The 5' region contains a CpG island, and the poly(A)(+) tail has an atypical 5'-GATAAA-3' signal. We analysed DUTT1 for mutations in lung, breast and kidney cancers, no inactivating mutations were detected by PCR-SSCP. However, seven germline missense changes were found and characterized. DUTT1 expression was not detectable in one out of 18 breast tumour lines analysed by RT-PCR. Bisulfite sequencing of the promoter region of DUTT1 gene in the HTB-19 breast tumour cell line (not expressing DUTT1) showed complete hypermethylation of CpG sites within the promoter region of the DUTT1 gene (-244 to +27 relative to the translation start site). The expression of DUTT1 gene was reactivated in HTB-19 after treatment with the demethylating agent 5-aza-2'-deoxycytidine. The same region was also found to be hypermethylated in six out of 32 (19%) primary invasive breast carcinomas and eight out of 44 (18%) primary clear cell renal cell carcinomas (CC-RCC) and in one out of 26 (4%) primary NSCLC tumours. Furthermore 80% of breast and 75% of CC-RCC tumours showing DUTT1 methylation had allelic losses for 3p12 markers hence obeying Knudson's two hit hypothesis. Our findings suggest that DUTT1 warrants further analysis as a candidate for

  9. Cubesat Proximity Operations Demonstration (CPOD)

    Science.gov (United States)

    Villa, Marco; Martinez, Andres; Petro, Andrew

    2015-01-01

    The CubeSat Proximity Operations Demonstration (CPOD) project will demonstrate rendezvous, proximity operations and docking (RPOD) using two 3-unit (3U) CubeSats. Each CubeSat is a satellite with the dimensions 4 inches x 4 inches x 13 inches (10 centimeters x 10 centimeters x 33 centimeters) and weighing approximately 11 pounds (5 kilograms). This flight demonstration will validate and characterize many new miniature low-power proximity operations technologies applicable to future missions. This mission will advance the state of the art in nanosatellite attitude determination,navigation and control systems, in addition to demonstrating relative navigation capabilities.The two CPOD satellites are scheduled to be launched together to low-Earth orbit no earlier than Dec. 1, 2015.

  10. Allelic variation of the inducible costimulator (ICOS) gene: detection of polymorphisms, analysis of the promoter region, and extended haplotype estimation

    DEFF Research Database (Denmark)

    Andersen, A.D.H.; Lange, Marianne; Lillevang, S.T.

    2003-01-01

    , consistent with the [T](n) and the [GT](n) regions reported in a Japanese study. Putative haplotypes for the established SNP and repeat polymorphisms have been estimated by computational analysis. Sequencing of similar to3500 by of the upstream region of ICOS revealed an additional eight SNP of which two...

  11. International Regional Patterns of R&D Networks Involving Low Tech SMEs

    Directory of Open Access Journals (Sweden)

    Aurora A.C. Teixeira

    2013-03-01

    Full Text Available A large number of studies have emphasized the spatial proximity of economic activity and its relation to the spatiality of knowledge creation in various types of connections. Far less attention has been paid to the understanding of the determinants of ‘cultural’ and geographical proximity in international R&D cooperation projects involving SMEs and the role of the quality of the Regional Innovation System (RIS. Using a database of completed European Cooperative Research projects, we conclude that: 1 technologically more complex projects are more likely to involve ‘culturally’ and geographically distant partners; 2 RIS related variables determine ‘cultural’ proximity but not geographical proximity; 3 at first sight surprisingly, international cooperation projects involving the 1st promoters of innovation-led regions (high patent propensity and high human capital levels are culturally more distant.

  12. Promoting biogas production and using it as transport fuel in the Helsinki region; Suunnitelma liikennebiokaasun tuotannon ja kaeytoen edistaemiseksi Helsingin seudulla

    Energy Technology Data Exchange (ETDEWEB)

    Rasi, S.; Havukainen, J.; Uusitalo, V.; Andersson, R.; Manninen, K.; Aro-Heinilae, E.; Rintala, J.

    2012-11-01

    The main objective of the project was to promote biogas production and its use as transport fuel. The aims in the four Finnish and two Estonian case areas were to reduce the amount and improve the sustainable use of waste and sludge, to promote biogas production, to start biogas use as transport fuel and to provide tools for implementing the aims. The total biomethane potential in the Helsinki region corresponds to approximately 450 GWh/a. The most potential user for biomethane is public transport. The total amount of biomethane would suffice for 80% of the busses operating in the Helsinki region. Using biogas as a transport fuel instead of energy production in the Helsinki region would result in emission reductions (13 000 t{sub CO2,eq}/a). However if the fuel replacing biogas in energy production would be renewable, the emission reductions would be significantly greater. The economical assessment indicates that the production of biogas is economically feasible if all the produced gas can be sold. Biogas produced near the natural gas grid can also be transported to the Helsinki region where there are better possibilities to find uses for it. In this way, for example, gas that is produced in Kymenlaakso but is not consumed there can be transported via the natural gas grid, assuming that the production plant is reasonably close to the grid. (orig.)

  13. Health-care users, key community informants and primary health care workers' views on health, health promotion, health assets and deficits: qualitative study in seven Spanish regions.

    Science.gov (United States)

    Pons-Vigués, Mariona; Berenguera, Anna; Coma-Auli, Núria; Pombo-Ramos, Haizea; March, Sebastià; Asensio-Martínez, Angela; Moreno-Peral, Patricia; Mora-Simón, Sara; Martínez-Andrés, Maria; Pujol-Ribera, Enriqueta

    2017-06-13

    Although some articles have analysed the definitions of health and health promotion from the perspective of health-care users and health care professionals, no published studies include the simultaneous participation of health-care users, primary health care professionals and key community informants. Understanding the perception of health and health promotion amongst these different stakeholders is crucial for the design and implementation of successful, equitable and sustainable measures that improve the health and wellbeing of populations. Furthermore, the identification of different health assets and deficits by the different informants will generate new evidence to promote healthy behaviours, improve community health and wellbeing and reduce preventable inequalities. The objective of this study is to explore the concept of health and health promotion and to compare health assets and deficits as identified by health-care users, key community informants and primary health care workers with the ultimate purpose to collect the necessary data for the design and implementation of a successful health promotion intervention. A descriptive-interpretive qualitative research was conducted with 276 participants from 14 primary care centres of 7 Spanish regions. Theoretical sampling was used for selection. We organized 11 discussion groups and 2 triangular groups with health-care users; 30 semi-structured interviews with key community informants; and 14 discussion groups with primary health care workers. A thematic content analysis was carried out. Health-care users and key community informants agree that health is a complex, broad, multifactorial concept that encompasses several interrelated dimensions (physical, psychological-emotional, social, occupational, intellectual, spiritual and environmental). The three participants' profiles consider health promotion indispensable despite defining it as complex and vague. In fact, most health-care users admit to having

  14. Attitudes, Beliefs and Predictors of Male Circumcision Promotion among Medical University Students in a Traditionally Non-Circumcising Region

    Directory of Open Access Journals (Sweden)

    Maria Ganczak

    2017-09-01

    Full Text Available Objective: To evaluate the beliefs of medical university students regarding male circumcision (MC, as well as attitudes and the predictors of its promotion in the case of adults at risk of HIV. Methods: A cross-sectional survey was conducted between 2013–2016 at the Medical University in Szczecin, Poland, among final year Polish/foreign students from Northern Europe, using a standardized questionnaire. Results: There were 539 participants, median age 25 years, 40.8% males, and 66.8% were Polish nationals. The MC rate was 16.7%. Regarding HIV/AIDS knowledge, 66.6% of the students scored more than 75%; and, 34.2% knew that MC reduces the risk of HIV infection. One in eleven respondents (9.1% believed that circumcised men felt more intense sexual pleasure. More than half of the respondents (54.8% declared that they would recommend MC to adult patients at risk for HIV. The belief that circumcised men felt more intense sexual pleasure, and knowledge on MC regarding HIV risk reduction was associated with greater odds of recommending adult MC (OR = 3.35 and OR = 2.13, respectively. Conclusions: Poor knowledge of its benefits and a low willingness to promote the procedure—strongly dependent on personal beliefs—suggest that medical students may need additional training to help them to discuss MC more openly with adult men at risk for HIV infection. Knowledge may be an effective tool when making decisions regarding MC promotion.

  15. Sequence of the 5'-flanking region and promoter activity of the human mucin gene MUC5B in different phenotypes of colon cancer cells.

    Science.gov (United States)

    Van Seuningen, I; Perrais, M; Pigny, P; Porchet, N; Aubert, J P

    2000-06-15

    Control of gene expression in intestinal cells is poorly understood. Molecular mechanisms that regulate transcription of cellular genes are the foundation for understanding developmental and differentiation events. Mucin gene expression has been shown to be altered in many intestinal diseases and especially cancers of the gastrointestinal tract. Towards understanding the transcriptional regulation of a member of the 11p15.5 human mucin gene cluster, we have characterized 3.55 kb of the 5'-flanking region of the human mucin gene MUC5B, including the promoter, the first two exons and the first intron. We report here the promoter activity of successively 5'-truncated sections of 956 bases of this region by fusing it to the coding region of a luciferase reporter gene. The transcription start site was determined by primer-extension analysis. The region upstream of the transcription start site is characterized by the presence of a TATA box at bases -32/-26, DNA-binding elements for transcription factors c-Myc, N-Myc, Sp1 and nuclear factor kappaB as well as putative activator protein (AP)-1-, cAMP-response-element-binding protein (CREB)-, hepatocyte nuclear factor (HNF)-1-, HNF-3-, TGT3-, gut-enriched Krüppel factor (GKLF)-, thyroid transcription factor (TTF)-1- and glucocorticoid receptor element (GRE)-binding sites. Intron 1 of MUC5B was also characterized, it is 2511 nucleotides long and contains a DNA segment of 259 bp in which are clustered eight tandemly repeated GA boxes and a CACCC box that bind Sp1. AP-2alpha and GATA-1 nuclear factors were also shown to bind to their respective cognate elements in intron 1. In transfection studies the MUC5B promoter showed a cell-specific activity as it is very active in mucus-secreting LS174T cells, whereas it is inactive in Caco-2 enterocytes and HT-29 STD (standard) undifferentiated cells. Within the promoter, maximal transcription activity was found in a segment covering the first 223 bp upstream of the transcription start

  16. Compound heterozygous SLC19A3 mutations further refine the critical promoter region for biotin-thiamine-responsive basal ganglia disease.

    Science.gov (United States)

    Whitford, Whitney; Hawkins, Isobel; Glamuzina, Emma; Wilson, Francessa; Marshall, Andrew; Ashton, Fern; Love, Donald R; Taylor, Juliet; Hill, Rosamund; Lehnert, Klaus; Snell, Russell G; Jacobsen, Jessie C

    2017-11-01

    Mutations in the gene SLC19A3 result in thiamine metabolism dysfunction syndrome 2, also known as biotin-thiamine-responsive basal ganglia disease (BTBGD). This neurometabolic disease typically presents in early childhood with progressive neurodegeneration, including confusion, seizures, and dysphagia, advancing to coma and death. Treatment is possible via supplement of biotin and/or thiamine, with early treatment resulting in significant lifelong improvements. Here we report two siblings who received a refined diagnosis of BTBGD following whole-genome sequencing. Both children inherited compound heterozygous mutations from unaffected parents; a missense single-nucleotide variant (p.G23V) in the first transmembrane domain of the protein, and a 4808-bp deletion in exon 1 encompassing the 5' UTR and minimal promoter region. This deletion is the smallest promoter deletion reported to date, further defining the minimal promoter region of SLC19A3 Unfortunately, one of the siblings died prior to diagnosis, but the other is showing significant improvement after commencement of therapy. This case demonstrates the power of whole-genome sequencing for the identification of structural variants and subsequent diagnosis of rare neurodevelopmental disorders. © 2017 Whitford et al.; Published by Cold Spring Harbor Laboratory Press.

  17. Congenital anomalies and proximity to landfill sites.

    LENUS (Irish Health Repository)

    Boyle, E

    2004-01-01

    The occurrence of congenital anomalies in proximity to municipal landfill sites in the Eastern Region (counties Dublin, Kildare, Wicklow) was examined by small area (district electoral division), distance and clustering tendancies in relation to 83 landfills, five of which were major sites. The study included 2136 cases of congenital anomaly, 37,487 births and 1423 controls between 1986 and 1990. For the more populous areas of the region 50% of the population lived within 2-3 km of a landfill and within 4-5 km for more rural areas. In the area-level analysis, the standardised prevalence ratios, empirical and full Bayesian modelling, and Kulldorff\\'s spatial scan statistic found no association between the residential area of cases and location of landfills. In the case control analysis, the mean distance of cases and controls from the nearest landfill was similar. The odds ratios of cases compared to controls for increasing distances from all landfills and major landfills showed no significant difference from the baseline value of 1. The kernel and K methods showed no tendency of cases to cluster in relationship to landfills. In conclusion, congenital anomalies were not found to occur more commonly in proximity to municipal landfills.

  18. Scattering Effects in Proximity Effect Tunneling Spectroscopy.

    Science.gov (United States)

    Gai, Wei

    PETS (Proximity Effect Tunneling Spectroscopy) technique has been applied to Niobium/Yttrium and Niobium/Lutetium bilayers. We have determined electron - phonon interaction parameter lambda_{rm e -ph} is 0.55 for Yttrium and 0.67 for Lutetium. Spin fluctuations parameter lambda_{ rm S} is 0.20 for Yttrium and 0.33 for Lutetium. We found that the large spin fluctuations in Yttrium and Lutetium has responsibility to the absence of superconductivity in them. Our results have given a reasonable explanation of high superconducting transition temperature in them under high pressure. The large reflection coefficient and strong diffuse scattering at Nb/Y and Nb/Lu interface has been discovered and it should have strong influence on the transport properties of metallic superlattices. From the modeling study of elastic scattering in proximity effect tunnel junctions, we have explained why some conventional made high {rm T_{C}} superconducting tunnel junctions give ideal like characteristics in the gap region but variable strength phonon structures in the phonon region.

  19. Primate TNF Promoters Reveal Markers of Phylogeny and Evolution of Innate Immunity

    Science.gov (United States)

    Baena, Andres; Ligeiro, Filipa; Diop, Ousmane M.; Brieva, Claudia; Gagneux, Pascal; O'Brien, Stephen J.; Ryder, Oliver A.; Goldfeld, Anne E.

    2007-01-01

    Background Tumor necrosis factor (TNF) is a critical cytokine in the immune response whose transcriptional activation is controlled by a proximal promoter region that is highly conserved in mammals and, in particular, primates. Specific single nucleotide polymorphisms (SNPs) upstream of the proximal human TNF promoter have been identified, which are markers of human ancestry. Methodology/Principal findings Using a comparative genomics approach we show that certain fixed genetic differences in the TNF promoter serve as markers of primate speciation. We also demonstrate that distinct alleles of most human TNF promoter SNPs are identical to fixed nucleotides in primate TNF promoters. Furthermore, we identify fixed genetic differences within the proximal TNF promoters of Asian apes that do not occur in African ape or human TNF promoters. Strikingly, protein-DNA binding assays and gene reporter assays comparing these Asian ape TNF promoters to African ape and human TNF promoters demonstrate that, unlike the fixed differences that we define that are associated with primate phylogeny, these Asian ape-specific fixed differences impair transcription factor binding at an Sp1 site and decrease TNF transcription induced by bacterial stimulation of macrophages. Conclusions/significance Here, we have presented the broadest interspecies comparison of a regulatory region of an innate immune response gene to date. We have characterized nucleotide positions in Asian ape TNF promoters that underlie functional changes in cell type- and stimulus-specific activation of the TNF gene. We have also identified ancestral TNF promoter nucleotide states in the primate lineage that correspond to human SNP alleles. These findings may reflect evolution of Asian and African apes under a distinct set of infectious disease pressures involving the innate immune response and TNF. PMID:17637837

  20. A Peptide Derived from the HIV-1 gp120 Coreceptor-Binding Region Promotes Formation of PAP248-286 Amyloid Fibrils to Enhance HIV-1 Infection.

    Directory of Open Access Journals (Sweden)

    Jinquan Chen

    Full Text Available Semen is a major vehicle for HIV transmission. Prostatic acid phosphatase (PAP fragments, such as PAP248-286, in human semen can form amyloid fibrils to enhance HIV infection. Other endogenous or exogenous factors present during sexual intercourse have also been reported to promote the formation of seminal amyloid fibrils.Here, we demonstrated that a synthetic 15-residue peptide derived from the HIV-1 gp120 coreceptor-binding region, designated enhancing peptide 2 (EP2, can rapidly self-assemble into nanofibers. These EP2-derivated nanofibers promptly accelerated the formation of semen amyloid fibrils by PAP248-286, as shown by Thioflavin T (ThT and Congo red assays. The amyloid fibrils presented similar morphology, assessed via transmission electron microscopy (TEM, in the presence or absence of EP2. Circular dichroism (CD spectroscopy revealed that EP2 accelerates PAP248-286 amyloid fibril formation by promoting the structural transition of PAP248-286 from a random coil into a cross-β-sheet. Newly formed semen amyloid fibrils effectively enhanced HIV-1 infection in TZM-bl cells and U87 cells by promoting the binding of HIV-1 virions to target cells.Nanofibers composed of EP2 promote the formation of PAP248-286 amyloid fibrils and enhance HIV-1 infection.

  1. SHORT COMMUNICATION PROXIMATE COMPOSITION, MINERAL ...

    African Journals Online (AJOL)

    Preferred Customer

    SHORT COMMUNICATION. PROXIMATE COMPOSITION, MINERAL CONTENT AND ANTINUTRITIONAL. FACTORS OF SOME CAPSICUM (Capsicum annum) VARIETIES GROWN IN. ETHIOPIA. Esayas K.1, Shimelis A.2, Ashebir F.3, Negussie R.3, Tilahun B.4 and Gulelat D.4*. 1Hawassa University, Department of Food ...

  2. Mouse model of proximal tubule endocytic dysfunction.

    Science.gov (United States)

    Weyer, Kathrin; Storm, Tina; Shan, Jingdong; Vainio, Seppo; Kozyraki, Renata; Verroust, Pierre J; Christensen, Erik I; Nielsen, Rikke

    2011-11-01

    Several studies have indicated the central role of the megalin/cubilin multiligand endocytic receptor complex in protein reabsorption in the kidney proximal tubule. However, the poor viability of the existing megalin-deficient mice precludes further studies and comparison of homogeneous groups of mice. Megalin- and/or cubilin-deficient mice were generated using a conditional Cre-loxP system, where the Cre gene is driven by the Wnt4 promoter. Kidney tissues from the mice were analysed for megalin and cubilin expression by quantitative reverse transcription-polymerase chain reaction, western blotting and immunohistochemistry. Renal albumin uptake was visualized by immunohistochemistry. Twenty-four-hour urine samples were collected in metabolic cages and analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and western blotting. Urinary albumin/creatinine ratios were measured by ELISA and the alkaline picrate method. The Meg(lox/lox);Cre(+), Cubn(lox/lox);Cre(+) and Meg(lox/lox), Cubn(lox/lox);Cre(+) mice were all viable, fertile and developed normal kidneys. Megalin and/or cubilin expression, assessed by immunohistology and western blotting, was reduced by >89%. Consistent with this observation, the mice excreted megalin and cubilin ligands such as transferrin and albumin in addition to low-molecular weight proteins. We further show that megalin/cubilin double-deficient mice excrete albumin with an average of 1.45 ± 0.54 mg/day, suggesting a very low albumin concentration in the glomerular ultrafiltrate. We report here the efficient genetic ablation of megalin, cubilin or both, using a Cre transgene driven by the Wnt4 promoter. The viable megalin/cubilin double-deficient mice now allow for detailed large-scale group analysis, and we anticipate that the mice will be of great value as an animal model for proximal tubulopathies with disrupted endocytosis.

  3. Polymorphism in the regulatory region located more than 1.1 kilobases 5' to the start site of transcription, the promoter region, and exon 1 of the HLA-G gene

    DEFF Research Database (Denmark)

    Hviid, T V; Sørensen, Steen; Morling, N

    1999-01-01

    in certain disorders of pregnancy. We have studied the DNA sequences of the putative regulatory region located more than 1.1 kilobases 5' from the start site of transcription (a 244 bp HindIII/EcoRI fragment) of the HLA-G gene and of the promoter region to detect any possible polymorphism. We detected one...... into two groups based on the detected polymorphism. The nucleotide substitutions may have implications for the binding of nuclear factors to the regulatory regions. To our knowledge this is the first study of any polymorphism in the 5'-flanking sequences to the HLA-G gene. Further studies are needed......The non-classic Human Leucocyte Antigen class Ib molecule, HLA-G, is expressed on the invasive, extra-villous cytotrophoblast in human placenta. HLA-G protects against natural killer (NK)-cell-mediated lysis and may modulate the secretion of cytokines. Aberrant expression of HLA-G has been reported...

  4. The potential risk of left subclavian artery injury from excessively long thoracic pedicle screws placed in the proximal thoracic regions of Lenke type 2 adolescent idiopathic scoliosis patients and normal teenagers: an anatomical study.

    Science.gov (United States)

    Jiang, Jun; Qian, Bang-Ping; Qiu, Yong; Wang, Bin; Yu, Yang; Zhu, Ze-Zhang

    2016-10-01

    The altered anatomic positions of important structures adjacent to the vertebrae in adolescent idiopathic scoliosis (AIS) patients have been comprehensively investigated by previous radiographic studies. However, no study has evaluated the altered position of left subclavian artery (SA) in these patients. The purpose of this study is to evaluate the altered position of left subclavian artery in AIS patients with a double thoracic curve pattern. Nineteen Lenke type 2 AIS patients and thirteen normal teenagers were included in this study. Axial computed tomography images at T2 and T3 levels were obtained in all these subjects to evaluate the subclavian artery-vertebral angle (SAVA, defined as 0° when the artery was located directly lateral to the left and 180° when directly lateral to the right) and subclavian artery-vertebral distance (SAVD, the shortest distance between the artery and vertebral body). The percentage of left subclavian arteries at potential risk of injury from excessively long pedicle screws was calculated. The SAVA was significantly larger in AIS patients than that in normal teenagers at both T2 and T3 levels (P teenagers at both T2 and T3 levels (P teenagers. The left SA is located much closer to the vertebrae in the proximal thoracic curve of Lenke type 2 AIS patients when compared with normal teenagers. The spine surgeons should be aware of such altered position of left SA and choose appropriate pedicle length to avoid anterior cortical penetration in Lenke type 2 AIS patients.

  5. A promoter in the coding region of the calcium channel gene CACNA1C generates the transcription factor CCAT.

    Directory of Open Access Journals (Sweden)

    Natalia Gomez-Ospina

    Full Text Available The C-terminus of the voltage-gated calcium channel Cav1.2 encodes a transcription factor, the calcium channel associated transcriptional regulator (CCAT, that regulates neurite extension and inhibits Cav1.2 expression. The mechanisms by which CCAT is generated in neurons and myocytes are poorly understood. Here we show that CCAT is produced by activation of a cryptic promoter in exon 46 of CACNA1C, the gene that encodes CaV1.2. Expression of CCAT is independent of Cav1.2 expression in neuroblastoma cells, in mice, and in human neurons derived from induced pluripotent stem cells (iPSCs, providing strong evidence that CCAT is not generated by cleavage of CaV1.2. Analysis of the transcriptional start sites in CACNA1C and immune-blotting for channel proteins indicate that multiple proteins are generated from the 3' end of the CACNA1C gene. This study provides new insights into the regulation of CACNA1C, and provides an example of how exonic promoters contribute to the complexity of mammalian genomes.

  6. Chelerythrine down regulates expression of VEGFA, BCL2 and KRAS by arresting G-Quadruplex structures at their promoter regions

    Science.gov (United States)

    Jana, Jagannath; Mondal, Soma; Bhattacharjee, Payel; Sengupta, Pallabi; Roychowdhury, Tanaya; Saha, Pranay; Kundu, Pallob; Chatterjee, Subhrangsu

    2017-01-01

    A putative anticancer plant alkaloid, Chelerythrine binds to G-quadruplexes at promoters of VEGFA, BCL2 and KRAS genes and down regulates their expression. The association of Chelerythrine to G-quadruplex at the promoters of these oncogenes were monitored using UV absorption spectroscopy, fluorescence anisotropy, circular dichroism spectroscopy, CD melting, isothermal titration calorimetry, molecular dynamics simulation and quantitative RT-PCR technique. The pronounced hypochromism accompanied by red shifts in UV absorption spectroscopy in conjunction with ethidium bromide displacement assay indicates end stacking mode of interaction of Chelerythrine with the corresponding G-quadruplex structures. An increase in fluorescence anisotropy and CD melting temperature of Chelerythrine-quadruplex complex revealed the formation of stable Chelerythrine-quadruplex complex. Isothermal titration calorimetry data confirmed that Chelerythrine-quadruplex complex formation is thermodynamically favourable. Results of quantative RT-PCR experiment in combination with luciferase assay showed that Chelerythrine treatment to MCF7 breast cancer cells effectively down regulated transcript level of all three genes, suggesting that Chelerythrine efficiently binds to in cellulo quadruplex motifs. MD simulation provides the molecular picture showing interaction between Chelerythrine and G-quadruplex. Binding of Chelerythrine with BCL2, VEGFA and KRAS genes involved in evasion, angiogenesis and self sufficiency of cancer cells provides a new insight for the development of future therapeutics against cancer.

  7. Isolation and identification of indigenous plant growth promoting rhizobacteria from Himalayan region of Kashmir and their effect on improving growth and nutrient contents of maize (Zea mays L.)

    Science.gov (United States)

    Zahid, Mahwish; Abbasi, M. Kaleem; Hameed, Sohail; Rahim, Nasir

    2015-01-01

    Introduction and exploitation of plant growth promoting rhizobacteria (PGPR) in agro-ecosystems enhance plant–microbes interactions that may affect ecosystems sustainability, agricultural productivity, and environmental quality. The present study was conducted to isolate and identify PGPRs associated with maize (Zea mays L.) from twenty sites of Himalayan region of Hajira-Rawalakot, Azad Jammu and Kashmir (AJK), Pakistan. A total of 100 isolates were isolated from these sites, out of which eight (HJR1, HJR2, HJR3, HJR4, HJR5, MR6, HJR7, HJR8) were selected in vitro for their plant growth promoting ability (PGPA) including phosphorus solubilization, indole-3-acetic acid (IAA) production and N2 fixation. The 16S rRNA gene sequencing technique was used for molecular identity and authentication. Isolates were then further tested for their effects on growth and nutrient contents of maize (Z. mays L.) under pouch and pot conditions. The 16S rRNA gene sequencing and phylogenetic analysis identified these isolates belong to Pseudomonas and Bacillus genera. The isolates promoted plant growth by solubilizing soil P which ranged between 19.2 and 35.6 μg mL-1. The isolates HJR1, HJR2, HJR3, and HJR5 showed positive activity in acetylene reduction assay showing their N2-fixation potential. All eight isolates showed the potential to produce IAA in the range of 0.9–5.39 μg mL-1 and promote plant growth. Results from a subsequent pot experiment indicated PGPRs distinctly increased maize shoot and root length, shoot and root dry weight, root surface area, leaf surface area, shoot and root N and P contents. Among the eight isolates, HR3 showed a marked P-solubilizing activity, plant growth-promoting attributes, and the potential to be developed as a biofertilizers for integrated nutrient management strategies. PMID:25852667

  8. Isolation and identification of indigenous plant growth promoting rhizobacteria from Himalayan region of Kashmir and their effect on improving growth and nutrient contents of maize (Zea mays L.).

    Science.gov (United States)

    Zahid, Mahwish; Abbasi, M Kaleem; Hameed, Sohail; Rahim, Nasir

    2015-01-01

    Introduction and exploitation of plant growth promoting rhizobacteria (PGPR) in agro-ecosystems enhance plant-microbes interactions that may affect ecosystems sustainability, agricultural productivity, and environmental quality. The present study was conducted to isolate and identify PGPRs associated with maize (Zea mays L.) from twenty sites of Himalayan region of Hajira-Rawalakot, Azad Jammu and Kashmir (AJK), Pakistan. A total of 100 isolates were isolated from these sites, out of which eight (HJR1, HJR2, HJR3, HJR4, HJR5, MR6, HJR7, HJR8) were selected in vitro for their plant growth promoting ability (PGPA) including phosphorus solubilization, indole-3-acetic acid (IAA) production and N2 fixation. The 16S rRNA gene sequencing technique was used for molecular identity and authentication. Isolates were then further tested for their effects on growth and nutrient contents of maize (Z. mays L.) under pouch and pot conditions. The 16S rRNA gene sequencing and phylogenetic analysis identified these isolates belong to Pseudomonas and Bacillus genera. The isolates promoted plant growth by solubilizing soil P which ranged between 19.2 and 35.6 μg mL(-1). The isolates HJR1, HJR2, HJR3, and HJR5 showed positive activity in acetylene reduction assay showing their N2-fixation potential. All eight isolates showed the potential to produce IAA in the range of 0.9-5.39 μg mL(-1) and promote plant growth. Results from a subsequent pot experiment indicated PGPRs distinctly increased maize shoot and root length, shoot and root dry weight, root surface area, leaf surface area, shoot and root N and P contents. Among the eight isolates, HR3 showed a marked P-solubilizing activity, plant growth-promoting attributes, and the potential to be developed as a biofertilizers for integrated nutrient management strategies.

  9. Isolation and Identification of Indigenous Plant Growth Promoting Rhizobacteria from Himalayan Region of Kashmir and their Effect on Improving Growth and Nutrient Contents of Maize (Zea Mays L.

    Directory of Open Access Journals (Sweden)

    Mahwish eZahid

    2015-03-01

    Full Text Available IIntroduction and exploitation of plant growth promoting rhizobacteria (PGPR in agro-ecosystems enhance plant-microbes interactions that may affect ecosystems sustainability, agricultural productivity and environmental quality. The present study was conducted to isolate and identify PGPRs associated with maize (Zea mays L. from twenty sites of Himalayan region of Hajira-Rawalakot, Azad Jammu and Kashmir (AJK, Pakistan. A total of one hundred isolates were isolated from these sites, out of which eight (HJR1, HJR2, HJR3, HJR4, HJR5, MR6, HJR7, HJR8 were selected in vitro for their plant growth promoting ability (PGPA including phosphorus solubilization, indole acetic acid (IAA production and N2 fixation. The 16S rRNA gene sequencing technique was used for molecular identity and authentication. Isolates were then further tested for their effects on growth and nutrient contents of maize (Zea mays L. under pouch and pot conditions. The 16S rRNA gene sequencing and phylogenetic analysis identified these isolates belong to Pseudomonas and Bacillus genera. The isolates promoted plant growth by solubilizing soil P which ranged between 19.2 and 35.6 µgmL−1. The isolates HJR1, HJR2, HJR3 and HJR5 showed positive activity in acetylene reduction assay showing their N2-fixation potential. All eight isolates showed the potential to produce IAA in the range of 0.9−5.39 µgmL−1 and promote plant growth. Results from a subsequent pot experiment indicated PGPRs distinctly increased maize shoot and root length, shoot and root dry weight, root surface area, leaf surface area, shoot and root N and P contents. Among the eight isolates, HR3 showed a marked P-solubilizing activity, plant growth-promoting attributes, and the potential to be developed as a biofertilizers for integrated nutrient management strategies

  10. Low frequency of mutations in the core promoter and precore regions of hepatitis B virus in anti-HBe positive Brazilian carriers

    Directory of Open Access Journals (Sweden)

    Niel Christian

    2001-07-01

    Full Text Available Abstract Background Mutations in the core promoter and precore regions of the hepatitis B virus (HBV genome, notably the double substitution (AGG to TGA at nt positions 1762-1764 in the core promoter, and the precore stop codon mutation G to A at nt 1896, can often explain the anti-HBe phenotype in chronic carriers. However, the A1896 mutation is restricted to HBV isolates that have T at nt 1858. The double substitution at positions 1762-1764 has been described to occur preferentially in patients infected with strains showing C instead of T at nt 1858. Results HBV DNAs from 29 anti-HBe Brazilian samples were characterized by nucleotide sequencing of PCR products from precore region. Among them, 18 isolates presented C at nt 1858 (mostly genotype A strains. The 11 remaining isolates (genotypes D and F had T1858. The stop codon mutation at nt 1896 was found in seven isolates (24% of the total and 63% of the isolates that had T1858. The frequency of the double substitution at positions 1762-1764 was surprisingly low (20% among C1858 isolates. An association between A1896 and TGA 1762-1764 mutations was observed among genotype D isolates: these showed either none of the two mutations or both. Furthermore, strains mutated at positions 1896 and/or 1762-1764 also presented an elevated number of other, less common substitutions in the core promoter and precore regions. Conclusions The data reported here are not in accordance with some reports from other parts of the world. In half of the isolates, none of the mutations previously described could explain the anti-HBe phenotype.

  11. Factor H binds to the hypervariable region of many Streptococcus pyogenes M proteins but does not promote phagocytosis resistance or acute virulence

    DEFF Research Database (Denmark)

    Gustafsson, Caj Ulrik Mattias; Lannergård, Jonas; Nilsson, Olof Rickard

    2013-01-01

    represents a distinct ligand-binding domain. The isolated HVRs specifically interacted with FH among all human serum proteins, interacted with the same region in FH and showed species specificity, but exhibited little or no antigenic cross-reactivity. Although these findings suggested that FH recruited...... to an M protein promotes virulence, studies in transgenic mice did not demonstrate a role for bound FH during acute infection. Moreover, phagocytosis tests indicated that ability to bind FH is neither sufficient nor necessary for S. pyogenes to resist killing in whole human blood. While these data shed...

  12. Photoactivated In Vivo Proximity Labeling.

    Science.gov (United States)

    Beck, David B; Bonasio, Roberto

    2017-06-19

    Identification of molecular interactions is paramount to understanding how cells function. Most available technologies rely on co-purification of a protein of interest and its binding partners. Therefore, they are limited in their ability to detect low-affinity interactions and cannot be applied to proteins that localize to difficult-to-solubilize cellular compartments. In vivo proximity labeling (IPL) overcomes these obstacles by covalently tagging proteins and RNAs based on their proximity in vivo to a protein of interest. In IPL, a heterobifunctional probe comprising a photoactivatable moiety and biotin is recruited by a monomeric streptavidin tag fused to a protein of interest. Following UV irradiation, candidate interacting proteins and RNAs are covalently biotinylated with tight spatial and temporal control and subsequently recovered using biotin as an affinity handle. Here, we describe experimental protocols to discover novel protein-protein and protein-RNA interactions using IPL. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  13. TURKEY AS A REGIONAL LOGISTIC HUB IN PROMOTION OF REVIVALING ANCIENT SILK ROUTE BETWEEN EUROPE AND ASIA

    OpenAIRE

    Acar, Avni; Bentyn, Zbigniew; Kocaoglu, Batuhan

    2015-01-01

    Since the ancient times the path between two continents led always through Turkey. Valuable merchandise traveled the famous Silk Road and allows creating a profitable trade for both sides of the known world. From international logistic perspective this process although risky and costly was a condition for future development of both regions. Today is also visible that maintaining an efficient and save route between both mentioned economically potent parts of the world is a crucial condition fo...

  14. Prox-1 Automated Proximity Operations

    Science.gov (United States)

    2016-01-13

    on demonstrating the functionality required to meet minimum mission success criteria. The minimum mission includes on- orbit spacecraft checkout of...also includes deployment of LightSail-B from the P-POD, and imaging of LightSail-B for 20 minutes as it recedes from Prox-1. small satellite ; proximity...criteria. The minimum mission includes on- orbit spacecraft checkout of all spacecraft subsystems, including flight qualification of the following new

  15. Immediate-early gene region of human cytomegalovirus trans-activates the promoter of human immunodeficiency virus

    Energy Technology Data Exchange (ETDEWEB)

    Davis, M.G.; Kenney, S.C.; Kamine, J.; Pagano, J.S.; Huang, E.S.

    1987-12-01

    Almost all homosexual patients with acquired immunodeficiency syndrome are also actively infected with human cytomegalovirus (HCMV). The authors have hypothesized that an interaction between HCMV and human immunodeficiency virus (HIV), the agent that causes acquired immunodeficiency syndrome, may exist at a molecular level and contribute to the manifestations of HIV infection. In this report, they demonstrate that the immediate-early gene region of HCMV, in particular immediate-early region 2, trans-activates the expression of the bacterial gene chloramphenicol acetyltransferase that is fused to the HIV long terminal repeat and carried by plasmid pHIV-CAT. The HCMV immediate-early trans-activator increases the level of mRNA from the plamid pHIV-CAT. The sequences of HIV that are responsive to trans-activation by the HDMV immediate-early region are distinct from HIV sequences that are required for response to the HIV tat. The stimulation of HIV gene expression by HDMV gene functions could enhance the consequences of HIV infection in persons with previous or concurrent HCMV infection.

  16. Enhancement of expression of survivin promoter-driven CD/TK double suicide genes by the nuclear matrix attachment region in transgenic gastric cancer cells.

    Science.gov (United States)

    Niu, Ying; Li, Jian-Sheng; Luo, Xian-Run

    2014-01-25

    This work aimed to study a novel transgenic expression system of the CD/TK double suicide genes enhanced by the nuclear matrix attachment region (MAR) for gene therapy. The recombinant vector pMS-CD/TK containing the MAR-survivin promoter-CD/TK cassette was developed and transfected into human gastric cancer SGC-7901 cells. Expression of the CD/TK genes was detected by quantitative real-time PCR (qPCR) and Western blot. Cell viability and apoptosis were measured using the methyl thiazolyl tetrazolium (MTT) assay and flow cytometry. When the MAR fragment was inserted into the upstream of the survivin promoter, the qPCR result showed that the expression of the CD/TK genes significantly increased 7.7-fold in the transgenic SGC-7901 cells with plasmid pMS-CD/TK compared with that without MAR. MTT and flow cytometry analyses indicated that treatment with the prodrugs (5-FC+GCV) significantly decreased the cellular survival rate and enhanced the cellular apoptosis in the SGC-7901 cells. The expression of the CD/TK double suicide genes driven by the survivin promoter can be enhanced by the MAR fragment in human gastric cancer cells. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Environmental stress affects DNA methylation of a CpG rich promoter region of serotonin transporter gene in a nurse cohort.

    Science.gov (United States)

    Alasaari, Jukka S; Lagus, Markus; Ollila, Hanna M; Toivola, Auli; Kivimäki, Mika; Vahtera, Jussi; Kronholm, Erkki; Härmä, Mikko; Puttonen, Sampsa; Paunio, Tiina

    2012-01-01

    Shift-working nurses are exposed to a stressful work environment, which puts them at an increased risk for burnout and depression. We explored the effect of environmental stress on serotonin transporter gene (SLC6A4) promoter methylation among nurses from high and low work stress environments. Using bisulfite sequencing, we investigated the methylation status of five CpG residues of a CpG-rich region in the promoter of SLC6A4 by comparing female shift working nurses from a high work stress environment (n = 24) to low work stress environment (n = 25). We also analyzed the association of 5-HTTLPR polymorphism at 5' end of SLC6A4. Work stress was assessed by the Karasek's Model and possible signs of burnout or depression were measured by the Maslach Burnout Index General Survey and Beck Depression Index. Methylation levels were assessed by bisulfite sequencing of DNA extracted from peripheral blood leucocytes. Restriction enzyme treatment followed by standard PCR was used to identify 5-HTTLPR genotypes. We found that nurses in the high stress environment had significantly lower promoter methylation levels at all five CpG residues compared to nurses in the low stress environment (pburnout was not significantly associated to methylation levels. However, when mutually adjusted for both, burnout and work stress were significant contributors (p = 0.038 and pdepressed mood in long-term stress.

  18. Inducible CTCF insulator delays the IgH 3' regulatory region-mediated activation of germline promoters and alters class switching.

    Science.gov (United States)

    Braikia, Fatima-Zohra; Oudinet, Chloé; Haddad, Dania; Oruc, Zeliha; Orlando, Domenico; Dauba, Audrey; Le Bert, Marc; Khamlichi, Ahmed Amine

    2017-06-06

    Class switch recombination (CSR) plays an important role in adaptive immune response by enabling mature B cells to switch from IgM expression to the expression of downstream isotypes. CSR is preceded by inducible germline (GL) transcription of the constant genes and is controlled by the 3' regulatory region (3'RR) in a stimulus-dependent manner. Why the 3'RR-mediated up-regulation of GL transcription is delayed to the mature B-cell stage is presently unknown. Here we show that mice devoid of an inducible CTCF binding element, located in the α constant gene, display a marked isotype-specific increase of GL transcription in developing and resting splenic B cells and altered CSR in activated B cells. Moreover, insertion of a GL promoter downstream of the CTCF insulator led to premature activation of the ectopic promoter. This study provides functional evidence that the 3'RR has a developmentally controlled potential to constitutively activate GL promoters but that this activity is delayed, at least in part, by the CTCF insulator, which borders a transcriptionally active domain established by the 3'RR in developing B cells.

  19. Temporal transcription of the lactococcal temperate phage TP901-1 and DNA sequence of the early promoter region

    DEFF Research Database (Denmark)

    Madsen, Hans Peter Lynge; Hammer, Karin

    1998-01-01

    , of which at least two (the integrase gene and putative repressor) are needed for lysogeny, and the divergent and longer transcriptional unit from PL, presumably encoding functions required for the lytic life cycle. ORFs with homology to proteins involved in DNA replication were identified on the latter......Transcriptional analysis by Northern blotting identified clusters of early, middle and late transcribed regions of the temperate lactococcal bacteriophage TP901-1 during one-step growth experiments. The latent period was found to be 65 min and the burst size 40 +/- 10. The eight early transcripts...

  20. Nucleotide sequence of the promoter-distal region of the tra operon of plasmid R100, including traI (DNA helicase I) and traD genes.

    Science.gov (United States)

    Yoshioka, Y; Fujita, Y; Ohtsubo, E

    1990-07-05

    The nucleotide sequence of the promoter-distal region of the tra operon of R100 was determined. There are five open reading frames in the region between traT and finO, and their protein products were identified. Nucleotide sequences of plasmid F corresponding to the junction regions among the open reading frames seen in R100 were also determined. Comparison of these nucleotide sequences revealed strong homology in the regions containing traD, traI and an open reading frame (named orfD). The TraD protein (83,899 Da) contains three hydrophobic regions, of which two are located near the amino-terminal region. This protein also contains a possible ATP-binding consensus sequence at the amino-terminal region and a characteristic repeated peptide sequence (Gln-Gln-Pro)10 at the carboxy-terminal region. The TraI protein (191,679 Da) contains the sequence motif conserved in an ATP-dependent DNA helicase superfamily in its carboxy-terminal region. The protein product of orfD, which is probably a new tra gene (named traX), contains 65% hydrophobic amino acids, especially rich in alanine and leucine. There exist non-homologous regions between R100 and F that could be represented as four I-D (insertion or deletion) loops in heteroduplex molecules. Assignment of each loop to the strand of R100 or F was , however, found to be the reverse from that previously assumed. The three I-D loops that were located between traT and traD, between traD and traI, and between traI and finO had no terminal inverted repeat sequences nor had they any homology with known insertion sequences, while the fourth was IS3, located within the finO gene of F. The sequences in the I-D loops, except IS3, may also code for proteins that are, however, likely to be nonessential for transfer of plasmids.

  1. ESR1 gene promoter region methylation in free circulating DNA and its correlation with estrogen receptor protein expression in tumor tissue in breast cancer patients.

    Science.gov (United States)

    Martínez-Galán, Joaquina; Torres-Torres, Blanca; Núñez, María Isabel; López-Peñalver, Jesús; Del Moral, Rosario; Ruiz De Almodóvar, José Mariano; Menjón, Salomón; Concha, Angel; Chamorro, Clara; Ríos, Sandra; Delgado, Juan Ramón

    2014-02-04

    Tumor expression of estrogen receptor (ER) is an important marker of prognosis, and is predictive of response to endocrine therapy in breast cancer. Several studies have observed that epigenetic events, such methylation of cytosines and deacetylation of histones, are involved in the complex mechanisms that regulate promoter transcription. However, the exact interplay of these factors in transcription activity is not well understood. In this study, we explored the relationship between ER expression status in tumor tissue samples and the methylation of the 5' CpG promoter region of the estrogen receptor gene (ESR1) isolated from free circulating DNA (fcDNA) in plasma samples from breast cancer patients. Patients (n = 110) with non-metastatic breast cancer had analyses performed of ER expression (luminal phenotype in tumor tissue, by immunohistochemistry method), and the ESR1-DNA methylation status (fcDNA in plasma, by quantitative methylation specific PCR technique). Our results showed a significant association between presence of methylated ESR1 in patients with breast cancer and ER negative status in the tumor tissue (p = 0.0179). There was a trend towards a higher probability of ESR1-methylation in those phenotypes with poor prognosis i.e. 80% of triple negative patients, 60% of HER2 patients, compared to 28% and 5.9% of patients with better prognosis such as luminal A and luminal B, respectively. Silencing, by methylation, of the promoter region of the ESR1 affects the expression of the estrogen receptor protein in tumors of breast cancer patients; high methylation of ESR1-DNA is associated with estrogen receptor negative status which, in turn, may be implicated in the patient's resistance to hormonal treatment in breast cancer. As such, epigenetic markers in plasma may be of interest as new targets for anticancer therapy, especially with respect to endocrine treatment.

  2. Simple Shared Motifs (SSM in conserved region of promoters: a new approach to identify co-regulation patterns

    Directory of Open Access Journals (Sweden)

    Théret Nathalie

    2011-09-01

    Full Text Available Abstract Background Regulation of gene expression plays a pivotal role in cellular functions. However, understanding the dynamics of transcription remains a challenging task. A host of computational approaches have been developed to identify regulatory motifs, mainly based on the recognition of DNA sequences for transcription factor binding sites. Recent integration of additional data from genomic analyses or phylogenetic footprinting has significantly improved these methods. Results Here, we propose a different approach based on the compilation of Simple Shared Motifs (SSM, groups of sequences defined by their length and similarity and present in conserved sequences of gene promoters. We developed an original algorithm to search and count SSM in pairs of genes. An exceptional number of SSM is considered as a common regulatory pattern. The SSM approach is applied to a sample set of genes and validated using functional gene-set enrichment analyses. We demonstrate that the SSM approach selects genes that are over-represented in specific biological categories (Ontology and Pathways and are enriched in co-expressed genes. Finally we show that genes co-expressed in the same tissue or involved in the same biological pathway have increased SSM values. Conclusions Using unbiased clustering of genes, Simple Shared Motifs analysis constitutes an original contribution to provide a clearer definition of expression networks.

  3. GDNF Schwann cells in hydrogel scaffolds promote regional axon regeneration, remyelination and functional improvement after spinal cord transection in rats.

    Science.gov (United States)

    Chen, Bingkun K; Madigan, Nicolas N; Hakim, Jeffrey S; Dadsetan, Mahrokh; McMahon, Siobhan S; Yaszemski, Michael J; Windebank, Anthony J

    2017-03-10

    Positively-charged oligo[poly(ethylene glycol)fumarate] (OPF+ ) is a biodegradable hydrogel used for spinal cord injury repair. We compared scaffolds containing primary Schwann cells (SCs) to scaffolds delivering SCs genetically modified to secrete high concentrations of glial cell-derived neurotrophic factor (GDNF). Multichannel OPF+ scaffolds loaded with SCs or GDNF-SCs were implanted into transected rat spinal cords for 4 weeks. GDNF-SCs promoted regeneration of more axons into OPF+ scaffolds (2773.0 ± 396.0) than primary SC OPF+ scaffolds (1666.0 ± 352.2) (p = 0.0491). This increase was most significant in central and ventral-midline channels of the scaffold. Axonal remyelination was quantitated by stereologic analysis. Increased myelination of regenerating axons was observed in the GDNF-SC group. Myelinating cell and axon complexes were formed by host SCs and not by implanted cells or host oligodendrocytes. Fast Blue retrograde tracing studies determined the rostral-caudal directionality of axonal growth. The number of neurons that projected axons rostrally through the GDNF-SC scaffolds was higher (7929 ± 1670) than in animals with SC OPF+ scaffolds (1069 ± 241.5) (p OPF+ scaffolds partially recovered locomotor function at weeks 3 and 4 following surgery. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  4. Transcriptional downregulation of rice rpL32 gene under abiotic stress is associated with removal of transcription factors within the promoter region.

    Directory of Open Access Journals (Sweden)

    Pradipto Mukhopadhyay

    Full Text Available BACKGROUND: The regulation of ribosomal proteins in plants under stress conditions has not been well studied. Although a few reports have shown stress-specific post-transcriptional and translational mechanisms involved in downregulation of ribosomal proteins yet stress-responsive transcriptional regulation of ribosomal proteins is largely unknown in plants. METHODOLOGY/PRINCIPAL FINDINGS: In the present work, transcriptional regulation of genes encoding rice 60S ribosomal protein L32 (rpL32 in response to salt stress has been studied. Northern and RT-PCR analyses showed a significant downregulation of rpL32 transcripts under abiotic stress conditions in rice. Of the four rpL32 genes in rice genome, the gene on chromosome 8 (rpL32_8.1 showed a higher degree of stress-responsive downregulation in salt sensitive rice variety than in tolerant one and its expression reverted to its original level upon withdrawal of stress. The nuclear run-on and promoter:reporter assays revealed that the downregulation of this gene is transcriptional and originates within the promoter region. Using in vivo footprinting and electrophoretic mobility shift assay (EMSA, cis-elements in the promoter of rpL32_8.1 showing reduced binding to proteins in shoots of salt stressed rice seedlings were identified. CONCLUSIONS: The present work is one of the few reports on study of stress downregulated genes. The data revealed that rpL32 gene is transcriptionally downregulated under abiotic stress in rice and that this transcriptional downregulation is associated with the removal of transcription factors from specific promoter elements.

  5. Workshop to promote the ratification of the protocol on heavy metals across the entire UN ECE region

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-12-15

    Within the workshop of the German Federal Environment Agency (Dessau-Rosslau, Federal Republic of Germany) at 14th to 16th May, 2008 in Yerevan (Armenia), the following lectures were held: (1) The convention and its protocols - framework and requirements (Tea Aulavuo); (2) Development of the heavy metals protocol up to now (D. Jost); (3) Experiences in transposing the obligations of the HM protocol into national law (Ivan Angelov); (4) Evaluation of concentrations of air pollutants and depositions of HM over the EECCA region (Ilia Ilyin); (5) The effectiveness of the HM protocol - emission reductions and costs (TNO-study) (M. van het Bolscher); (6) Technologies and techniques and their emission reduction potential and costs (Andre Peeters Weem); (7) Synergies of reduction of HM and particulate matter (Katja Kraus); (8) Critical loads / critical levels and effects of HM - integrated assessment (Jean-Paul Hettelingh); (9) Additional technical measures / options and their reduction potential (M. van het Bolscher); (10) Overview of the situation in the EECCA region - evaluation of a questionnaire of the Secretariat of the LRTAP Convention and ideas on revising the protocol and its annexes (Johan Sliggers); (11) Future aims of the TF (Katja Kraus).

  6. Proximal focal humeral deficiency in a large breed dog.

    Science.gov (United States)

    Kalff, S; Gemmill, T

    2012-01-01

    A 26-week-old female Boerboel was referred for evaluation of progressive left thoracic limb lameness. Computed tomography and radiographic evaluation revealed radiolucency of the caudal region of the proximal humeral metaphysis, absence of the humeral head, and gross distortion of the glenoid. Given the severe glenohumeral deformation, arthrodesis of the left shoulder was performed using orthogonal locking bone plates, lag screw fixation, and bone grafting. Despite late implant failure, arthrodesis was successful in this case, and satisfactory limb function was restored. To the author's knowledge, this is the first report of a case of a focal developmental deficiency of the proximal humerus reported in a dog.

  7. PROXIMATE AND ELEMENTAL COMPOSITION OF WHITE GRUBS

    African Journals Online (AJOL)

    DR. AMINU

    PROXIMATE AND ELEMENTAL COMPOSITION OF WHITE GRUBS. 1 Alhassan, A. J. 1M .S. Sule, 1J. ... ABSTRACT. This study determined the proximate and mineral element composition of whole white grubs using standard methods of analysis. Proximate ... days, before pulverized to powder and kept in plastic container.

  8. Rehabilitation and Prevention of Proximal Hamstring Tendinopathy.

    Science.gov (United States)

    Beatty, Nicholas R; Félix, Ioonna; Hettler, Jessica; Moley, Peter J; Wyss, James F

    Proximal hamstring tendinopathy (PHT) comprises a small but significant portion of hamstring injuries in athletes, especially runners. PHT is a chronic condition that is clinically diagnosed but can be supported with imaging. The main presenting complaint is pain in the lower gluteal or ischial region that may or may not radiate along the hamstrings in the posterior thigh. There is little scientific evidence on which to base the rehabilitation management of PHT. Treatment is almost always conservative, with a focus on activity modification, addressing contributing biomechanical deficiencies, effective tendon loading including eccentric training, and ultrasound-guided interventional procedures which may facilitate rehabilitation. Surgery is limited to recalcitrant cases or those involving concomitant high-grade musculotendinous pathology. The keys to PHT management include early and accurate diagnosis, optimal rehabilitation to allow for a safe return to preinjury activity level, and preventative strategies to reduce risk of reinjury.

  9. C-terminal region of MAP7 domain containing protein 3 (MAP7D3 promotes microtubule polymerization by binding at the C-terminal tail of tubulin.

    Directory of Open Access Journals (Sweden)

    Saroj Yadav

    Full Text Available MAP7 domain containing protein 3 (MAP7D3, a newly identified microtubule associated protein, has been shown to promote microtubule assembly and stability. Its microtubule binding region has been reported to consist of two coiled coil motifs located at the N-terminus. It possesses a MAP7 domain near the C-terminus and belongs to the microtubule associated protein 7 (MAP7 family. The MAP7 domain of MAP7 protein has been shown to bind to kinesin-1; however, the role of MAP7 domain in MAP7D3 remains unknown. Based on the bioinformatics analysis of MAP7D3, we hypothesized that the MAP7 domain of MAP7D3 may have microtubule binding activity. Indeed, we found that MAP7 domain of MAP7D3 bound to microtubules as well as enhanced the assembly of microtubules in vitro. Interestingly, a longer fragment MDCT that contained the MAP7 domain (MD with the C-terminal tail (CT of the protein promoted microtubule polymerization to a greater extent than MD and CT individually. MDCT stabilized microtubules against dilution induced disassembly. MDCT bound to reconstituted microtubules with an apparent dissociation constant of 3.0 ± 0.5 µM. An immunostaining experiment showed that MDCT localized along the length of the preassembled microtubules. Competition experiments with tau indicated that MDCT shares its binding site on microtubules with tau. Further, we present evidence indicating that MDCT binds to the C-terminal tail of tubulin. In addition, MDCT could bind to tubulin in HeLa cell extract. Here, we report a microtubule binding region in the C-terminal region of MAP7D3 that may have a role in regulating microtubule assembly dynamics.

  10. Human galectin-3 (Mac-2 antigen): Defining molecular switches of affinity to natural glycoproteins, structural and dynamic aspects of glycan binding by flexible ligand docking and putative regulatory sequences in the proximal promoter region

    NARCIS (Netherlands)

    Krzeminski, M.N.; Singh, T.; André, S.; Lensch, M.; Wu, A.M.; Bonvin, A.M.J.J.; Gabius, H.-J.

    2011-01-01

    Background: Human galectin-3 (Mac-2 antigen) is a cell-type-specific multifunctional effector owing to selective binding of distinct cell-surface glycoconjugates harboring β-galactosides. The structural basis underlying the apparent preferences for distinct glycoproteins and for expression is so far

  11. Sequential Proximal Tibial Stress Fractures associated with Prolonged usage of Methotrexate and Corticosteroids: A Case Report

    Directory of Open Access Journals (Sweden)

    Tan TJL

    2015-11-01

    Full Text Available Stress fractures of the proximal tibia metaphysis are rare in the elderly. We present a case of a 65-year old male who developed sequential proximal tibia stress fractures associated with prolonged usage of methotrexate and prednisolone within a span of 18 months. Magnetic Resonance Imaging revealed an incomplete stress fracture involving the medial proximal tibial region. The patient was treated with stemmed total knee arthroplasty (TKA bilaterally. Stress fractures should be considered in patients with atypical knee pain who have a history of methotrexate and prednisolone usage. TKA is an effective treatment in stress fractures of the proximal tibia.

  12. Finger Proximal Interphalangeal Joint Dislocation.

    Science.gov (United States)

    Ramponi, Denise; Cerepani, Mary Jo

    2015-01-01

    Finger dislocations are common injuries that are often managed by emergency nurse practitioners. A systematic physical examination following these injuries is imperative to avoid complications. Radiographic views, including the anteroposterior, lateral, and oblique views, are imperative to evaluate these finger dislocations. A dorsal dislocation of the proximal interphalangeal (PIP) joint is the most common finger dislocation type often easily reduced. A volar PIP dislocation can often be difficult to reduce and may result in finger deformity. Finger dislocations should be reduced promptly. Referral to an orthopedic hand specialist is required if the dislocation is unable to be reduced or if the finger joint is unstable following reduction attempts.

  13. Equilibrium properties of proximity effect

    Energy Technology Data Exchange (ETDEWEB)

    Esteve, D.; Pothier, H.; Gueron, S.; Birge, N.O.; Devoret, M.

    1996-12-31

    The proximity effect in diffusive normal-superconducting (NS) nano-structures is described by the Usadel equations for the electron pair correlations. We show that these equations obey a variational principle with a potential which generalizes the Ginzburg-Landau energy functional. We discuss simple examples of NS circuits using this formalism. In order to test the theoretical predictions of the Usadel equations, we have measured the density of states as a function of energy on a long N wire in contact with a S wire at one end, at different distances from the NS interface. (authors). 12 refs.

  14. Protein-DNA Interactions at the Opossum Npt2a Promoter are Dependent upon NHERF-1

    Directory of Open Access Journals (Sweden)

    Barbara J. Clark

    2016-06-01

    Full Text Available Background/Aims: Phosphate homeostasis is controlled by the renal reabsorption of Pi by the type IIa sodium phosphate cotransporter, Npt2a, which is localized in the proximal tubule brush border membrane. Regulation of Npt2a expression is a key control point to maintain phosphate homeostasis with most studies focused on regulating protein levels in the brush border membrane. Molecular mechanisms that control Npt2a mRNA, however, remain to be defined. We have reported that Npt2a mRNA and protein levels correlate directly with the expression of the Na+/H+ exchanger regulatory factor 1 (NHERF-1 using opossum kidney (OK cells and the NHERF-1-deficient OK-H cells. The goal of this study was to determine whether NHERF-1 contributes to transcriptional and/or post-transcriptional mechanisms controlling Npt2a mRNA levels. Methods: Npt2a mRNA half-life was compared between OK and NHERF-1 deficient OK-H cell lines. oNpt2a promoter-reporter gene assays and electrophoretic mobility shift assays (EMSA were used identify a NHERF-1 responsive region within the oNpt2a proximal promoter. Results: Npt2a mRNA half-life is the same in OK and OK-H cells. The NHERF-1 responsive region lies within the proximal promoter in a region that contains a highly conserved CAATT box and G-rich element. Specific protein-DNA complex formation with the CAATT element is altered by the absence of NHERF-1 (OK v OK-H EMSA although NHERF-1 does not directly contribute to complex formation. Conclusion: NHERF-1 helps maintain steady-state Npt2a mRNA levels in OK cells through indirect mechanisms that help promote protein-DNA interactions at the Npt2a proximal promoter.

  15. Protein-DNA Interactions at the Opossum Npt2a Promoter are Dependent upon NHERF-1.

    Science.gov (United States)

    Clark, Barbara J; Murray, Rebecca D; Salyer, Sarah A; Tyagi, Samuel C; Arumugam, Cibi; Khundmiri, Syed J; Lederer, Eleanor D

    2016-01-01

    Phosphate homeostasis is controlled by the renal reabsorption of Pi by the type IIa sodium phosphate cotransporter, Npt2a, which is localized in the proximal tubule brush border membrane. Regulation of Npt2a expression is a key control point to maintain phosphate homeostasis with most studies focused on regulating protein levels in the brush border membrane. Molecular mechanisms that control Npt2a mRNA, however, remain to be defined. We have reported that Npt2a mRNA and protein levels correlate directly with the expression of the Na+/H+ exchanger regulatory factor 1 (NHERF-1) using opossum kidney (OK) cells and the NHERF-1-deficient OK-H cells. The goal of this study was to determine whether NHERF-1 contributes to transcriptional and/or post-transcriptional mechanisms controlling Npt2a mRNA levels. Npt2a mRNA half-life was compared between OK and NHERF-1 deficient OK-H cell lines. oNpt2a promoter-reporter gene assays and electrophoretic mobility shift assays (EMSA) were used identify a NHERF-1 responsive region within the oNpt2a proximal promoter. Npt2a mRNA half-life is the same in OK and OK-H cells. The NHERF-1 responsive region lies within the proximal promoter in a region that contains a highly conserved CAATT box and G-rich element. Specific protein-DNA complex formation with the CAATT element is altered by the absence of NHERF-1 (OK v OK-H EMSA) although NHERF-1 does not directly contribute to complex formation. NHERF-1 helps maintain steady-state Npt2a mRNA levels in OK cells through indirect mechanisms that help promote protein-DNA interactions at the Npt2a proximal promoter. © 2016 The Author(s) Published by S. Karger AG, Basel.

  16. The OSMATER project: promotion of stone materials from the Verbano-Cusio-Ossola region (Italy) and the Canton Ticino (Switzerland).

    Science.gov (United States)

    Cavallo, Alessandro; Antonella Dino, Giovanna

    2013-04-01

    The OSMATER (sub-Alpine Observatory Materials Territory Restoration) project, funded by the Piedmont Region (Italy) and the European Community, involved four Italian scientific bodies (Polytechnic of Turin, University of Turin, University of Milan-Bicocca, University of Bologna) and Switzerland (SUPSI). The aim was to investigate the present and historical quarrying and processing activities in the cross-border area between the Ossola Valley (Italy) and the Canton Ticino (Switzerland), and the use of dimension stones in local and national architecture. These materials are in many ways a "unique case", for their abundance and lithological variety. In the past, their extraction, processing and application characterized in a decisive way the architectural and constructive culture, both in terms of prestigious architecture and civil buildings, establishing a relationship between "stones and culture", "territory and its resources". In recent years, many of these traditions are losing importance and interest: this results in a loss of knowledge and historical memory, due mainly to the drastic changes in the market. The loss of this knowledge is likely to become irreversible in the short term, with the disappearance of people and social groups depositary of tradition. We can deduce that the creation of an "observatory", like OSMATER, is desirable and essential indeed, if we want to preserve the historical memory of the stone industry of an entire production area. The OSMATER project aimed the knowledge, recovery and enhancement of the architectural and cultural heritage of the cross-border area, through the census and classification of rocks, quarries (both active and historical - since Roman age), monuments and construction techniques typical of the sub-Alpine region, in order to create a documentation centre through a dedicated website. The first phase of the project was devoted to the identification of architectural works built with stone materials, with particular

  17. Single nucleotide polymorphisms in the tumor necrosis factor-alpha gene promoter region alter the risk of psoriasis vulgaris and psoriatic arthritis: a meta-analysis.

    Science.gov (United States)

    Zhu, Junqing; Qu, Hongda; Chen, Xiaoguang; Wang, Hao; Li, Juan

    2013-01-01

    It has been confirmed that tumor necrosis factor-alpha (TNFα), a macrophage-derived pro-inflammatory cytokine, plays an important role in the pathogenesis of psoriasis vulgaris and psoriatic arthritis (PsV&PsA). In contrast, the reported association of TNFα gene promoter region single nucleotide polymorphisms (SNPs) and PsV&PsA has remained controversial. Accordingly, we performed a meta-analysis to provide new evidence that SNPs in the TNFα gene promoter region alter not only the risk of psoriasis vulgaris (PsV) or psoriatic arthritis (PsA) but also of PsV&PsA. Interrelated literature dated to October 2012 was acquired from the PubMed, ScienceDirect, and SpringerLink databases. The number of the genotypes and/or alleles for the TNFα promoter in the PsV and PsA and control subjects was obtained. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to calculate the risk of PsV and/or PsA with TNFα promoter SNPs. A total of 26 papers of 2159 for PsV (2129 normal controls) and 2360 for PsA (2997 normal controls) were included in our meta-analysis. The results showed that the variant genotype and allele of TNFα -308A/G was protective in pooled groups of patients with PsV&PsA (OR = 0.682, 0.750; 95% CI, 0.596-0.779, 0.653-0.861). However, the variant genotypes and alleles of TNFα -238A/G and -857T/C had an increased risk of PsV&PsA (OR = 2.493, 2.228, 1.536, 1.486, 95% CI, 1.777-3.498, 1.628-3.049, 1.336-1.767, 1.309-1.685). Moreover, the meta-analysis revealed a significant association between TNFα -238A/G and -857T/C polymorphism and PsA susceptibility (OR = 2.242, 2.052, 1.419, 1.465; 95% CI, 1.710-2.941, 1.614-2.610, 1.214-1.658, 1.277-1.681). In contrast, the variant genotypes and alleles of TNFα -308A/G proved to be protective against PsV (OR = 0.574, 0.650, 95% CI, 0.478-0.690, 0.556-0.759), whereas TNFα -238A/G was found to have a risk association (OR = 2.636, 2.223, 95% CI, 1.523-4.561, 1.317-3.751). SNPs in the TNFα gene promoter region

  18. Single nucleotide polymorphisms in the tumor necrosis factor-alpha gene promoter region alter the risk of psoriasis vulgaris and psoriatic arthritis: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Junqing Zhu

    Full Text Available BACKGROUND: It has been confirmed that tumor necrosis factor-alpha (TNFα, a macrophage-derived pro-inflammatory cytokine, plays an important role in the pathogenesis of psoriasis vulgaris and psoriatic arthritis (PsV&PsA. In contrast, the reported association of TNFα gene promoter region single nucleotide polymorphisms (SNPs and PsV&PsA has remained controversial. Accordingly, we performed a meta-analysis to provide new evidence that SNPs in the TNFα gene promoter region alter not only the risk of psoriasis vulgaris (PsV or psoriatic arthritis (PsA but also of PsV&PsA. METHODS: Interrelated literature dated to October 2012 was acquired from the PubMed, ScienceDirect, and SpringerLink databases. The number of the genotypes and/or alleles for the TNFα promoter in the PsV and PsA and control subjects was obtained. Odds ratios (ORs and 95% confidence intervals (CIs were used to calculate the risk of PsV and/or PsA with TNFα promoter SNPs. RESULTS: A total of 26 papers of 2159 for PsV (2129 normal controls and 2360 for PsA (2997 normal controls were included in our meta-analysis. The results showed that the variant genotype and allele of TNFα -308A/G was protective in pooled groups of patients with PsV&PsA (OR = 0.682, 0.750; 95% CI, 0.596-0.779, 0.653-0.861. However, the variant genotypes and alleles of TNFα -238A/G and -857T/C had an increased risk of PsV&PsA (OR = 2.493, 2.228, 1.536, 1.486, 95% CI, 1.777-3.498, 1.628-3.049, 1.336-1.767, 1.309-1.685. Moreover, the meta-analysis revealed a significant association between TNFα -238A/G and -857T/C polymorphism and PsA susceptibility (OR = 2.242, 2.052, 1.419, 1.465; 95% CI, 1.710-2.941, 1.614-2.610, 1.214-1.658, 1.277-1.681. In contrast, the variant genotypes and alleles of TNFα -308A/G proved to be protective against PsV (OR = 0.574, 0.650, 95% CI, 0.478-0.690, 0.556-0.759, whereas TNFα -238A/G was found to have a risk association (OR = 2.636, 2.223, 95% CI, 1.523-4.561, 1

  19. Single Nucleotide Polymorphisms in the Tumor Necrosis Factor-Alpha Gene Promoter Region Alter the Risk of Psoriasis Vulgaris and Psoriatic Arthritis: A Meta-Analysis

    Science.gov (United States)

    Zhu, Junqing; Qu, Hongda; Chen, Xiaoguang; Wang, Hao; Li, Juan

    2013-01-01

    Background It has been confirmed that tumor necrosis factor-alpha (TNFα), a macrophage-derived pro-inflammatory cytokine, plays an important role in the pathogenesis of psoriasis vulgaris and psoriatic arthritis (PsV&PsA). In contrast, the reported association of TNFα gene promoter region single nucleotide polymorphisms (SNPs) and PsV&PsA has remained controversial. Accordingly, we performed a meta-analysis to provide new evidence that SNPs in the TNFα gene promoter region alter not only the risk of psoriasis vulgaris (PsV) or psoriatic arthritis (PsA) but also of PsV&PsA. Methods Interrelated literature dated to October 2012 was acquired from the PubMed, ScienceDirect, and SpringerLink databases. The number of the genotypes and/or alleles for the TNFα promoter in the PsV and PsA and control subjects was obtained. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to calculate the risk of PsV and/or PsA with TNFα promoter SNPs. Results A total of 26 papers of 2159 for PsV (2129 normal controls) and 2360 for PsA (2997 normal controls) were included in our meta-analysis. The results showed that the variant genotype and allele of TNFα -308A/G was protective in pooled groups of patients with PsV&PsA (OR = 0.682, 0.750; 95% CI, 0.596-0.779, 0.653-0.861). However, the variant genotypes and alleles of TNFα -238A/G and -857T/C had an increased risk of PsV&PsA (OR = 2.493, 2.228, 1.536, 1.486, 95% CI, 1.777-3.498, 1.628-3.049, 1.336-1.767, 1.309-1.685). Moreover, the meta-analysis revealed a significant association between TNFα -238A/G and -857T/C polymorphism and PsA susceptibility (OR = 2.242, 2.052, 1.419, 1.465; 95% CI, 1.710-2.941, 1.614-2.610, 1.214-1.658, 1.277-1.681). In contrast, the variant genotypes and alleles of TNFα -308A/G proved to be protective against PsV (OR = 0.574, 0.650, 95% CI, 0.478-0.690, 0.556-0.759), whereas TNFα -238A/G was found to have a risk association (OR = 2.636, 2.223, 95% CI, 1.523-4.561, 1

  20. Chronic Fatigue Syndrome and DNA Hypomethylation of the Glucocorticoid Receptor Gene Promoter 1F Region: Associations With HPA Axis Hypofunction and Childhood Trauma.

    Science.gov (United States)

    Vangeel, Elise; Van Den Eede, Filip; Hompes, Titia; Izzi, Benedetta; Del Favero, Jurgen; Moorkens, Greta; Lambrechts, Diether; Freson, Kathleen; Claes, Stephan

    2015-10-01

    Chronic fatigue syndrome (CFS) has been associated with hypothalamic-pituitary-adrenal axis hypofunction and enhanced glucocorticoid receptor (GR) sensitivity. In addition, childhood trauma is considered a major risk factor for the syndrome. This study examines DNA methylation of the GR gene (NR3C1) in CFS and associations with childhood sexual and physical trauma. Quantification of DNA methylation within the 1F promoter region of NR3C1 was performed in 76 female patients (46 with no/mild and 30 with moderate/severe childhood trauma) and 19 healthy controls by using Sequenom EpiTYPER. Further, we examined the association of NR3C1-1F promoter methylation with the outcomes of the low-dose (0.5 mg) dexamethasone/corticotropin-releasing factor test in a subset of the study population. Mann-Whitney U tests and Spearman correlations were used for statistical analyses. Overall NR3C1-1F DNA methylation was lower in patients with CFS than in controls. After cytosine guanine dinucleotide (CpG)-specific analysis, CpG_1.5 remained significant after Bonferroni correction (adjusted p = .0014). Within the CFS group, overall methylation (ρ = 0.477, p = .016) and selective CpG units (CpG_1.5: ρ = 0.538, p = .007; CpG_12.13: ρ = 0.448, p = .025) were positively correlated with salivary cortisol after dexamethasone administration. There was no significant difference in NR3C1-1F methylation between traumatized and nontraumatized patients. We found evidence of NR3C1 promoter hypomethylation in female patients with CFS and the functional relevance of these differences was consistent with the hypothalamic-pituitary-adrenalaxis hypofunction hypothesis (GR hypersuppression). However, we found no evidence of an additional effect of childhood trauma on CFS via alterations in NR3C1 methylation.

  1. Further evidence that the rs1858830 C variant in the promoter region of the MET gene is associated with autistic disorder.

    Science.gov (United States)

    Jackson, Pamela B; Boccuto, Luigi; Skinner, Cindy; Collins, Julianne S; Neri, Giovanni; Gurrieri, Fiorella; Schwartz, Charles E

    2009-08-01

    Previous studies in three independent cohorts have shown that the rs1858830 C allele variant in the promoter region of the MET gene on chromosome 7q31 is associated with autism. Another study has found correlations between other alterations in the MET gene and autism in two unrelated cohorts. This study screened two cohorts, an Autistic Disorder cohort from South Carolina and a Pervasive Developmental Disorder (PDD) cohort from Italy, for the presence of the C allele variant in rs1858830. A significant increase in the C allele variant frequency was found in the South Carolina Autistic Disorder patients as compared to South Carolina Controls (chi(2)=5.8, df=1, P=0.02). In the South Carolina cohort, a significant association with Autistic Disorder was found when comparing the CC and CG genotypes to the GG genotype (odds ratio (OR)=1.64; 95% confidence interval (CI)=1.12-2.40; chi(2)=6.5, df=1, P=0.01) in cases and controls. In the Italian cohort, no significant association with PDD was found when comparing the CC or CG genotype to the GG genotype (OR=1.20; 95% CI=0.56-2.56; chi(2)=0.2, df=1, P=0.64). This study is the third independent study to find the rs1858830 C variant in the MET gene promoter to be associated with autism.

  2. Determination of methylated CpG sites in the promoter region of catechol-O-methyltransferase (COMT and their involvement in the etiology of tobacco smoking

    Directory of Open Access Journals (Sweden)

    Qing Xu

    2010-06-01

    Full Text Available We previously reported that catechol-O-methyltransferase (COMT is significantly associated with nicotine dependence (ND in humans. In this study, we examined whether there exists any difference in the extent of methylation of CpG dinucleotides in the promoter region of COMT in smokers and nonsmokers by analyzing the methylation status of cytosines at 33 CpG sites through direct sequencing of bisulfite-treated DNA (N = 50 per group. The cytosine was methylated at 13 of 33 CpG sites, and two of these sites showed significant differences between smokers and matched nonsmoker controls. Specifically, in the -193 CpG site, the degree of methylation was 19.1% in smokers and 13.2% in nonsmokers (P < 0.01. This finding was confirmed by methylation-specific PCR using an additional 100 smoker and 100 nonsmoker control samples, which showed the degree of methylation to be 22.2% in smokers and 18.3% in nonsmokers (P < 0.01. For the -39 CpG site, the degree of methylation was 9.2% in smokers, whereas no methylation was found in nonsmoker controls. Together, our findings provide the first molecular explanation at the epigenetic level for the association of ND with methylation of the COMT promoter, implying that methylation plays a role in smoking dependence.

  3. The beach as a setting for families' health promotion: a qualitative study with parents and children living in coastal regions in Southwest England.

    Science.gov (United States)

    Ashbullby, Katherine J; Pahl, Sabine; Webley, Paul; White, Mathew P

    2013-09-01

    This study explores the neglected issue of how families engage with beach environments in their local areas and use them in health promoting ways. Fifteen families with children aged 8-11 years living in coastal regions in Southwest England participated in individual semi-structured interviews. The findings indicate that beaches encouraged families to be physically active. Although families valued the opportunities for physical activity and active play afforded by beaches, the key health benefits emphasised were psychological, including experiencing fun, stress relief and engagement with nature. Increased social and family interaction was also highlighted as benefits. Despite perceiving health benefits, not all families regularly visited the beach. Barriers to visits included parents having limited time, cost of parking, lack of car access and cold weather. Parents played a key role in enabling visits by choosing to share these environments with their children. The social dimension of visits also encouraged families to make regular trips. The findings support the use of beach environments to promote families' health and wellbeing and positive relationships with nature. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. A Specific Mutation in the Promoter Region of the Silent cel Cluster Accounts for the Appearance of Lactose-Utilizing Lactococcus lactis MG1363

    Science.gov (United States)

    Solopova, Ana; Bachmann, Herwig; Teusink, Bas; Kok, Jan; Neves, Ana Rute

    2012-01-01

    The Lactococcus lactis laboratory strain MG1363 has been described to be unable to utilize lactose. However, in a rich medium supplemented with lactose as the sole carbon source, it starts to grow after prolonged incubation periods. Transcriptome analyses showed that L. lactis MG1363 Lac+ cells expressed celB, encoding a putative cellobiose-specific phosphotransferase system (PTS) IIC component, which is normally silent in MG1363 Lac− cells. Nucleotide sequence analysis of the cel cluster of a Lac+ isolate revealed a change from one of the guanines to adenine in the promoter region. We showed here that one particular mutation, taking place at increased frequency, accounts for the lactose-utilizing phenotype occurring in MG1363 cultures. The G-to-A transition creates a −10 element at an optimal distance from the −35 element. Thus, a fully active promoter is created, allowing transcription of the otherwise cryptic cluster. Nuclear magnetic resonance (NMR) spectroscopy results show that MG1363 Lac+ uses a novel pathway of lactose utilization. PMID:22660716

  5. Clinical significance of SNP (rs2596542 in histocompatibility complex class I-related gene A promoter region among hepatitis C virus related hepatocellular carcinoma cases

    Directory of Open Access Journals (Sweden)

    Amal A. Mohamed

    2017-07-01

    Full Text Available The major histocompatibility complex class I-related gene A (MICA is an antigen induced by stress and performs an integral role in immune responses as an anti-infectious and antitumor agent. This work was designed to investigate whether (SNP rs2596542C/T in MICA promoter region is predictive of liver cirrhosis (LC and hepatocellular carcinoma (HCC or not. Forty-seven healthy controls and 94 HCV-infected patients, subdivided into 47 LC and 47 HCC subjects were enrolled in this study. SNP association was studied using real time PCR and soluble serum MICA concentration was measured using ELISA. Results showed that heterozygous genotype rs2596542CT was significantly (P = 0.022 distributed between HCC and LC related CHC patients. The sMICA was significantly higher (P = 0.0001 among HCC and LC. No significant association (P = 0.56 between rs2596542CT genotypes and sMICA levels was observed. Studying SNP rs2596542C/T association with HCC and LC susceptibility revealed that statistical significant differences (P = 0.013, P = 0.027 were only observed between SNP rs2596542C/T and each of HCC and LC, respectively, versus healthy controls, indicating that the rs2596542C/T genetic variation is not a significant contributor to HCC development in LC patients. Moreover, the T allele was considered a risk factor for HCC and LC vulnerability in HCV patients (OR = 1.93 and 2.1, respectively, while the C allele contributes to decreasing HCC risk. Therefore, SNP (rs2596542C/T in MICA promoter region and sMICA levels might be potential useful markers in the assessment of liver disease progression to LC and HCC.

  6. Relation of shyness in grade school children to the genotype for the long form of the serotonin transporter promoter region polymorphism.

    Science.gov (United States)

    Arbelle, Shoshana; Benjamin, Jonathan; Golin, Moshe; Kremer, Ilana; Belmaker, Robert H; Ebstein, Richard P

    2003-04-01

    Studies have shown that genetic factors are significant in predisposing individuals to shyness and social phobia. Toward further elucidating the genetic structure of shyness, the authors examined four functional polymorphisms that make biological sense for contributing to the development of this phenotype: serotonin transporter promoter region 44 base pair insertion/deletion (5-HTTLPR), dopamine D(4) receptor exon III repeat (DRD4), catechol O-methyltransferase (COMT), and monoamine oxidase A promoter region repeat (MAO(A)). The authors assessed shyness after recruitment of a nonclinical sample (N=118, unscreened second-grade children) using a composite scale derived from questionnaires administered to the children, parents, and teachers. DNA from buccal smears successfully obtained from 98 children was genotyped by polymerase chain reaction methods for the 5-HTTLPR, DRD4, COMT, and MAO(A) polymorphisms. Significant correlations were observed for parents', teachers', and children's ratings of shyness, and Cronbach's alpha reliability was high for all three scales. A significant association was observed between the long 5-HTTLPR polymorphism and shyness, both by the functional classification of Lesch as well as by consideration of all three genotypes. No significant association was observed for the DRD4, COMT, or MAO(A) polymorphisms. This study provisionally identifies a common genetic polymorphism, 5-HTTLPR, that modestly (effect size=7%) contributed to greater shyness scores in a nonclinical group of second-grade students. These first findings may be relevant to previous reports that have shown an association between the 5-HTTLPR long form and obsessive-compulsive disorder and autism.

  7. Quantitative analysis of DNA methylation in the promoter region of the methylguanine-O(6) -DNA-methyltransferase gene by COBRA and subsequent native capillary gel electrophoresis.

    Science.gov (United States)

    Goedecke, Simon; Mühlisch, Jörg; Hempel, Georg; Frühwald, Michael C; Wünsch, Bernhard

    2015-12-01

    Along with histone modifications, RNA interference and delayed replication timing, DNA methylation belongs to the key processes in epigenetic regulation of gene expression. Therefore, reliable information about the methylation level of particular DNA fragments is of major interest. Herein the methylation level at two positions of the promoter region of the gene methylguanine-O(6) -DNA-Methyltransferase (MGMT) was investigated. Previously, it was demonstrated that the epigenetic status of this DNA region correlates with response to alkylating anticancer agents. An automated CGE method with LIF detection was established to separate the six DNA fragments resulting from combined bisulfite restriction analysis of the methylated and non-methylated MGMT promoter. In COBRA, the DNA was treated with bisulfite converting cytosine into uracil. During PCR uracil pairs with adenine, which changes the original recognition site of the restriction enzyme Taql. Artificial probes generated by mixing appropriate amounts of DNA after bisulfite treatment and PCR amplification were used for validation of the method. The methylation levels of these samples could be determined with high accuracy and precision. DNA samples prepared by mixing the corresponding clones first and then performing PCR amplification led to non-linear correlation between the corrected peak areas and the methylation levels. This effect is explained by slightly different PCR amplification of DNA with different sequences present in the mixture. The superiority of CGE over PAGE was clearly demonstrated. Finally, the established method was used to analyze the methylation levels of human brain tumor tissue samples. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Efficient Production of Bacillus thuringiensis Cry1AMod Toxins under Regulation of cry3Aa Promoter and Single Cysteine Mutations in the Protoxin Region

    Science.gov (United States)

    García-Gómez, Blanca I.; Sánchez, Jorge; Martínez de Castro, Diana L.; Ibarra, Jorge E.; Bravo, Alejandra

    2013-01-01

    Bacillus thuringiensis Cry1AbMod toxins are engineered versions of Cry1Ab that lack the amino-terminal end, including domain I helix α-1 and part of helix α-2. This deletion improves oligomerization of these toxins in solution in the absence of cadherin receptor and counters resistance to Cry1A toxins in different lepidopteran insects, suggesting that oligomerization plays a major role in their toxicity. However, Cry1AbMod toxins are toxic to Escherichia coli cells, since the cry1A promoter that drives its expression in B. thuringiensis has readthrough expression activity in E. coli, making difficult the construction of these CryMod toxins. In this work, we show that Cry1AbMod and Cry1AcMod toxins can be cloned efficiently under regulation of the cry3A promoter region to drive its expression in B. thuringiensis without expression in E. coli cells. However, p3A-Cry1Ab(c)Mod construction promotes the formation of Cry1AMod crystals in B. thuringiensis cells that were not soluble at pH 10.5 and showed no toxicity to Plutella xylostella larvae. Cysteine residues in the protoxin carboxyl-terminal end of Cry1A toxins have been shown to be involved in disulfide bond formation, which is important for crystallization. Six individual cysteine substitutions for serine residues were constructed in the carboxyl-terminal protoxin end of the p3A-Cry1AbMod construct and one in the carboxyl-terminal protoxin end of p3A-Cry1AcMod. Interestingly, p3A-Cry1AbMod C654S and C729S and p3A-Cry1AcMod C730S recover crystal solubility at pH 10.5 and toxicity to P. xylostella. These results show that combining the cry3A promoter expression system with single cysteine mutations is a useful system for efficient expression of Cry1AMod toxins in B. thuringiensis. PMID:24014526

  9. Environmental stress affects DNA methylation of a CpG rich promoter region of serotonin transporter gene in a nurse cohort.

    Directory of Open Access Journals (Sweden)

    Jukka S Alasaari

    Full Text Available Shift-working nurses are exposed to a stressful work environment, which puts them at an increased risk for burnout and depression. We explored the effect of environmental stress on serotonin transporter gene (SLC6A4 promoter methylation among nurses from high and low work stress environments.Using bisulfite sequencing, we investigated the methylation status of five CpG residues of a CpG-rich region in the promoter of SLC6A4 by comparing female shift working nurses from a high work stress environment (n = 24 to low work stress environment (n = 25. We also analyzed the association of 5-HTTLPR polymorphism at 5' end of SLC6A4. Work stress was assessed by the Karasek's Model and possible signs of burnout or depression were measured by the Maslach Burnout Index General Survey and Beck Depression Index. Methylation levels were assessed by bisulfite sequencing of DNA extracted from peripheral blood leucocytes. Restriction enzyme treatment followed by standard PCR was used to identify 5-HTTLPR genotypes.We found that nurses in the high stress environment had significantly lower promoter methylation levels at all five CpG residues compared to nurses in the low stress environment (p<0.01. There was no significant interaction of 5-HTTLPR genotype and work stress with methylation (p = 0.58. In unadjusted (bivariate analysis, burnout was not significantly associated to methylation levels. However, when mutually adjusted for both, burnout and work stress were significant contributors (p = 0.038 and p<0.0001 respectively to methylation levels.Our findings show that environmental stress is concurrent with decreased methylation of the SLC6A4 promoter. This may lead to increased transcriptional activity of the gene, increased reuptake of serotonin from synaptic clefts, and termination of the activity of serotonin. This could present a possible coping mechanism for environmental stress in humans that could eventually increase risk for disturbed functional

  10. The clinical significance of nucleotide G1613A and C1653T mutations in the core promoter region of hepatitis B virus

    Directory of Open Access Journals (Sweden)

    Peng-yu HUANG

    2016-04-01

    Full Text Available Objective  To evaluate the impact of hepatitis B virus (HBV genome G1613A and C1653T mutations on disease progression, viral replication capacity, and transcription activity of HBV core promoter (CP. Methods  A total of 258 patients were enrolled in the present study, including 65 patients with acute hepatitis B (AHB, 120 with chronic hepatitis B (CHB, and 73 with acute on chronic liver failure (ACLF. Serum HBV DNA was extracted from patients, and full-length HBV genome was amplified by PCR. The incidences of G1613A, C1653T and G1613A+C1653T in different groups were compared, and through functional experiments, the impact of mutants and wild-type virus on viral replication capacity and CP transcription activity was assessed. Results  Genotype B, C and D were the three detected genotypes in 285 patients, with detection rates of 22.2%, 76.2% and 1.6%, respectively. The incidences of G1613A, C1653T and G1613A+C1653T mutations increased with the disease exacerbation, and they were 13.70%, 31.80% and 45.20% in AHB patients (P<0.01, 2.30%, 16.30% and 27.40% in CHB patients (P<0.01, and 2.29%, 12.07% and 23.29% in ACLF patients (P<0.05. Compare with wild-type strain, the G1613A mutant strain of HBV increased the viral replication capacity by 6%, reduced HBsAg level and core promoter activity by 15% and 16.2%, and reduced HBeAg to undetectable level; the C1653T mutant strain increased the viral replication capacity, HBsAg level, and core promoter activity by 10%, 55% and 17.1%, respectively, and the HBeAg level was comparable to that of wild-type strain; the G1613A+C1653T mutant strain increased viral replication capacity, HBsAg level and HBeAg level by 7%, 66% and 227%, respectively, while it had no influence on core promoter activity. Conclusion The G1613A and C1653T mutation in CP region may increase HBV replication capacity and alter CP activity and HBV antigens expression, the doublet mutation of G1613A+C1653T shows synergic effect on these

  11. Conservation and promotion of the geological heritage in the «Ile-de-France» region (France): Establishment of a decision support-tool based on inventory

    Science.gov (United States)

    Auberger, Elise; Gély, Jean-Pierre; De Wever, Patrick; Merle, Didier

    2017-04-01

    Based on an initiative by the "Regional Commission of Geological Patrimony" (CRPG), the French state and the regional government of Ile-de-France co-financed the setting up of an inventory with the aim of safeguarding geological sites of patrimonial interest. This project forms part of larger scale policies, at the national and European level. Geological studies in the Paris region began as early as the 18th century, in the fields of cartography and paleontology. Later on, prominent scientists like G. Cuvier, A. Brongniart and A. d'Orbigny established the first concepts in sedimentology and stratigraphy through the description of Cenozoic fossil sites that rank amongst the richest in the world and geological formations in the Paris Basin. Eventually, later on, five historical stratotypes were established in the Ile-de-France region. Yet, at present, this geological heritage is constantly threatened by expanding urbanisation. To conserve this diverse geological patrimony, we have set up a protocol composed of 4 main actions: i) The exhaustive and objective referencing of geological sites in Ile-de-France. This information is centralised in a database, which currently comprises 639 sites (mainly of anthropic nature such as quarries) ii) The pre-selection of sites (298 out of the initial 639) based on sufficient accessibility and potential geological interest. iii) The use of a method of description and hierarchisation - following the guidelines of the National Geological Heritage Inventory Program (INPG) - on the pre-selected sites. iv) Establishment of a schedule specifying actions of geo-conservation which will take into account the patrimonial value of the sites, but also their threats, their juridical status and the socio-economic context of the region. The purpose of this program is to conserve a collection of geological sites that reflect the totality of the regional geology in Ile-de-France. The results of this study will be released to the general public and

  12. The effect of modular tapered fluted stems on proximal stress shielding in the human femur.

    Science.gov (United States)

    Hnat, William P; Conway, Justin S; Malkani, Arthur L; Yakkanti, Madhu R; Voor, Michael J

    2009-09-01

    The purpose of this study was to show a change in proximal femur surface strains following total hip arthroplasty and after the addition of BoneSource hydroxyapatite bone cement in the proximal region of an instrumented femur and to measure the surface strain on the proximal body. Seven third-generation composite femurs (Pacific Research Laboratories, Vashon, Wash) were instrumented with 12 uniaxial strain gages, 6 gages on the anterior face, and 6 gages on the posterior face of each femur. All femurs exhibited stress shielding since the strains in the proximal region were drastically reduced. There was a large decrease in strain in the mid-shaft region and small changes in strain in the distal region. The surface strains on the modular implant were relatively low.

  13. Complications in proximal humeral fractures.

    Science.gov (United States)

    Calori, Giorgio Maria; Colombo, Massimiliano; Bucci, Miguel Simon; Fadigati, Piero; Colombo, Alessandra Ines Maria; Mazzola, Simone; Cefalo, Vittorio; Mazza, Emilio

    2016-10-01

    Necrosis of the humeral head, infections and non-unions are among the most dangerous and difficult-to-treat complications of proximal humeral fractures. The aim of this work was to analyse in detail non-unions and post-traumatic bone defects and to suggest an algorithm of care. Treatment options are based not only on the radiological frame, but also according to a detailed analysis of the patient, who is classified using a risk factor analysis. This method enables the surgeon to choose the most suitable treatment for the patient, thereby facilitating return of function in the shortest possible time. The treatment of such serious complications requires the surgeon to be knowledgeable about the following possible solutions: increased mechanical stability; biological stimulation; and reconstructive techniques in two steps, with application of biotechnologies and prosthetic substitution. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Sequencing and G-quadruplex folding of the canine proto-oncogene KIT promoter region: might dog be used as a model for human disease?

    Directory of Open Access Journals (Sweden)

    Silvia Da Ros

    Full Text Available Downregulation of gene expression by induction of non-canonical DNA structures at promotorial level is a novel attractive anticancer strategy. In human, two guanine-rich sequences (h_kit1 and h_kit2 were identified in the promotorial region of oncogene KIT. Their stabilization into G-quadruplex structures can find applications in the treatment of leukemias, mastocytosis, gastrointestinal stromal tumor, and lung carcinomas which are often associated to c-kit mis-regulation. Also the most common skin cancer in domestic dog, mast cell tumor, is linked to a mutation and/or to an over-expression of c-kit, thus supporting dog as an excellent animal model. In order to assess if the G-quadruplex mediated mechanism of regulation of c-kit expression is conserved among the two species, herein we cloned and sequenced the canine KIT promoter region and we compared it with the human one in terms of sequence and conformational equilibria in physiologically relevant conditions. Our results evidenced a general conserved promotorial sequence between the two species. As experimentally confirmed, this grants that the conformational features of the canine kit1 sequence are substantially shared with the human one. Conversely, two isoforms of the kit2 sequences were identified in the analyzed dog population. In comparison with the human counterpart, both of them showed an altered distribution among several folded conformations.

  15. The future role of the professional associations in the promotion of tissue banking activities in Asia and the Pacific and in the Latin America regions.

    Science.gov (United States)

    Morales Pedraza, Jorge; Vajaradul, Yongyudh; Alvarez, Ines

    2011-11-01

    There are several important roles that the established professional associations [Asia-Pacific Association of Surgical Tissue Banking (APASTB) and Latin American Association of Tissue Banks (ALABAT)] could play for the promotion of tissue banking activities in Asia and the Pacific and in the Latin American regions in the future. The International Atomic Energy Agency (IAEA) and the World Health Organisation (WHO) could also play an important role in supporting the activities of both professional associations in the field of training, exchange of scientific information, the standardisation of national norms and regulations, the use of the IAEA documents, particularly the "Radiation Sterilisation of Tissue Allografts: Requirements for Validation and Routine Control. A Code of Practice", with the purpose to improve the quality of the activities carried out by the established tissue banks and the nuclear facilities in charge of the sterilisation of the processed tissues, and to increase tissue donations. The role of APASTB and ALABAT could be relevant and important for the improvement of the work of the established tissue banks in Asia and the Pacific and in the Latin American regions, and could increase the effectiveness and efficiency of their works, the improvement of management good practices and for increasing the awareness of the community on the importance of the activities carried out by the tissue banks, among others.

  16. The promoter and the 5'-untranslated region of rice metallothionein OsMT2b gene are capable of directing high-level gene expression in germinated rice embryos.

    Science.gov (United States)

    Wu, Chung-Shen; Chen, Dai-Yin; Chang, Chung-Fu; Li, Min-Jeng; Hung, Kuei-Yu; Chen, Liang-Jwu; Chen, Peng-Wen

    2014-05-01

    Critical regions within the rice metallothionein OsMT2b gene promoter are identified and the 5'-untranslated region (5'-UTR) is found essential for the high-level promoter activity in germinated transgenic rice embryos. Many metallothionein (MT) genes are highly expressed in plant tissues. A rice subfamily p2 (type 2) MT gene, OsMT2b, has been shown previously to exhibit the most abundant gene expression in young rice seedling. In the present study, transient expression assays and a transgenic approach were employed to characterize the expression of the OsMT2b gene in rice. We found that the OsMT2b gene is strongly and differentially expressed in germinated rice embryos during seed germination and seedling development. Histochemical staining analysis of transgenic rice carrying OsMT2b::GUS chimeric gene showed that high-level GUS activity was detected in germinated embryos and at the meristematic part of other tissues during germination. Deletion analysis of the OsMT2b promoter revealed that the 5'-flanking region of the OsMT2b between nucleotides -351 and -121 relative to the transcriptional initiation site is important for promoter activity in rice embryos, and this region contains the consensus sequences of G box and TA box. Our study demonstrates that the 5'-untranslated region (5'-UTR) of OsMT2b gene is not only necessary for the OsMT2b promoter activity, but also sufficient to augment the activity of a minimal promoter in both transformed cell cultures and germinated transgenic embryos in rice. We also found that addition of the maize Ubi intron 1 significantly enhanced the OsMT2b promoter activity in rice embryos. Our studies reveal that OsMT2b351-ubi(In) promoter can be applied in plant transformation and represents potential for driving high-level production of foreign proteins in transgenic rice.

  17. Proximate composition and antinutrient content of pumpkin ...

    African Journals Online (AJOL)

    Proximate composition and antinutrient content of pumpkin ( Cucurbita pepo ) and sorghum ( Sorghum bicolor ) flour blends fermented with Lactobacillus plantarum , Aspergillus niger and Bacillus subtilis.

  18. Silencing of Peroxiredoxin 2 and aberrant methylation of 33 CpG islands in putative promoter regions in human malignant melanomas.

    Science.gov (United States)

    Furuta, Junichi; Nobeyama, Yoshimasa; Umebayashi, Yoshihiro; Otsuka, Fujio; Kikuchi, Kanako; Ushijima, Toshikazu

    2006-06-15

    Aberrant methylation of promoter CpG islands (CGI) is involved in silencing of tumor suppressor genes and is also a potential cancer biomarker. Here, to identify CGIs aberrantly methylated in human melanomas, we did a genome-wide search using methylation-sensitive representational difference analysis. CGIs in putative promoter regions of 34 genes (ABHD9, BARHL1, CLIC5, CNNM1, COL2A1, CPT1C, DDIT4L, DERL3, DHRS3, DPYS, EFEMP2, FAM62C, FAM78A, FLJ33790, GBX2, GPR10, GPRASP1, HOXA9, HOXD11, HOXD12, HOXD13, p14ARF, PAX6, PRDX2, PTPRG, RASD1, RAX, REC8L1, SLC27A3, TGFB2, TLX2, TMEM22, TMEM30B, and UNC5C) were found to be methylated in at least 1 of 13 melanoma cell lines but not in two cultured normal melanocytes. Among these genes, Peroxiredoxin 2 (PRDX2) was expressed in normal melanocytes, and its expression was lost in melanomas with methylation. The loss of expression was restored by treatment of melanomas with a demethylating agent 5-aza-2'-deoxycytidine. In surgical melanoma specimens, methylation of PRDX2 was detected in 3 of 36 (8%). Furthermore, immunohistochemical analysis of PRDX2 showed that disappearance of immunoreactivity tends to associate with its methylation. PRDX2 was recently reported to be a negative regulator of platelet-derived growth factor signaling, and its silencing was suggested to be involved in melanomas. On the other hand, 12 CGIs were methylated in >or=9 of the 13 melanoma cell lines and are considered as candidate melanoma biomarkers.

  19. Polymorphisms in the promoter region of the human class II alcohol dehydrogenase (ADH4) gene affect both transcriptional activity and ethanol metabolism in Japanese subjects.

    Science.gov (United States)

    Kimura, Yukiko; Nishimura, Fusae T; Abe, Shuntaro; Fukunaga, Tatsushige; Tanii, Hideji; Saijoh, Kiyofumi

    2009-02-01

    Class II alcohol dehydrogenase (pi-ADH), encoded by alcohol dehydrogenase (ADH4), is considered to contribute to ethanol (EtOH) oxidation in the liver at high concentration. Four single nucleotide polymorphisms (SNPs) were found in the promoter region of this gene. Analysis of genotype distribution in 102 unrelated Japanese subjects revealed that four loci were in strong linkage disequilibrium and could be classified into three haplotypes. The effects of these polymorphisms on transcriptional activity were investigated in HepG2 cells. Transcriptional activity was significantly higher in cells with the -136A allele than in those with the -136C allele. To investigate whether this difference in transcriptional activity caused a difference in EtOH elimination, previous data on blood EtOH changes after 0.4 g/kg body weight alcohol ingestion were analyzed. When analyzed based on aldehyde dehydrogenase-2 gene (ALDH2) (487)Glu/Lys genotype, the significantly lower level of EtOH at peak in subjects with -136C/A and -136A/A genotype compared with subjects with -136C/C genotype indicated that -136 bp was a suggestive locus for differences in EtOH oxidation. This effect was observed only in subjects with ALDH2 (487)Glu/Glu. These results suggested that the SNP at -136bp in the ADH4 promoter had an effect on transcriptional regulation, and that the higher activity of the -136A allele compared with the -136C allele caused a lower level of blood EtOH after alcohol ingestion; that is, individuals with the -136A allele may consume more EtOH and might have a higher risk for development of alcohol dependence than those without the -136A allele.

  20. A functional single nucleotide polymorphism at the promoter region of cyclin A2 is associated with increased risk of colon, liver, and lung cancers.

    Science.gov (United States)

    Kim, Duk-Hwan; Park, Seong-Eun; Kim, Minseung; Ji, Yong Ick; Kang, Mi Yeon; Jung, Eun Hyun; Ko, Eunkyung; Kim, Yujin; Kim, Sung; Shim, Young Mog; Park, Joobae

    2011-09-01

    The objective of this was to identify functional single nucleotide polymorphisms (SNPs) in cyclin-dependent kinases (CDKs) and cyclins that are associated with risk of human cancer. First, 45 SNPs in CDKs and cyclins were analyzed in 106 lung cancers and 108 controls for a pilot study. One SNP (reference SNP [rs] 769236, +1 guanine to adenine [G→A]) at the promoter region of cyclin A2 (CCNA2) also was analyzed in 1989 cancers (300 breast cancers, 450 colorectal cancers, 450 gastric cancers, 367 hepatocellular carcinomas, and 422 lung cancers) and in 1096 controls. Genotyping was performed using matrix-assisted laser desorption-ionization/time-of-flight mass spectrometry. Transcriptional activity of the SNP according to the cell cycle was analyzed by using a luciferase reporter assay and fluorescence-activated cell sorting analysis in NIH3T3 cells. In the pilot study, the SNP (rs769236) was associated significantly with the risk of lung cancer. In the expanded study, multivariate logistic regression indicated that the AA homozygous variant of the SNP was associated significantly with the development of lung cancer (P hepatocellular carcinoma (P = .02) but not with breast cancer or gastric cancer. The luciferase activity of a 300-base pair construct that contained the A allele was 1.5-fold greater than the activity of a construct with the G allele in NIH3T3 cells. The high luciferase activity of constructs that contained the A allele did not change with cell cycle progression. The current results suggested that an SNP (rs769236) at the promoter of CCNA2 may be associated significantly with increased risk of colon, liver, and lung cancers. Cancer 2011 © 2011 American Cancer Society.

  1. Proximal location of mouse prostate epithelial stem cells

    OpenAIRE

    Tsujimura, Akira; Koikawa, Yasuhiro; Salm, Sarah; Takao, Tetsuya; Coetzee, Sandra; Moscatelli, David; Shapiro, Ellen; Lepor, Herbert; Sun, Tung-Tien; Wilson, E. Lynette

    2002-01-01

    Stem cells are believed to regulate normal prostatic homeostasis and to play a role in the etiology of prostate cancer and benign prostatic hyperplasia. We show here that the proximal region of mouse prostatic ducts is enriched in a subpopulation of epithelial cells that exhibit three important attributes of epithelial stem cells: they are slow cycling, possess a high in vitro proliferative potential, and can reconstitute highly branched glandular ductal structures in collagen gels. We propos...

  2. An Intergenic Region Shared by At4g35985 and At4g35987 in Arabidopsis thaliana Is a Tissue Specific and Stress Inducible Bidirectional Promoter Analyzed in Transgenic Arabidopsis and Tobacco Plants

    Science.gov (United States)

    Banerjee, Joydeep; Sahoo, Dipak Kumar; Dey, Nrisingha; Houtz, Robert L.; Maiti, Indu Bhushan

    2013-01-01

    On chromosome 4 in the Arabidopsis genome, two neighboring genes (calmodulin methyl transferase At4g35987 and senescence associated gene At4g35985) are located in a head-to-head divergent orientation sharing a putative bidirectional promoter. This 1258 bp intergenic region contains a number of environmental stress responsive and tissue specific cis-regulatory elements. Transcript analysis of At4g35985 and At4g35987 genes by quantitative real time PCR showed tissue specific and stress inducible expression profiles. We tested the bidirectional promoter-function of the intergenic region shared by the divergent genes At4g35985 and At4g35987 using two reporter genes (GFP and GUS) in both orientations in transient tobacco protoplast and Agro-infiltration assays, as well as in stably transformed transgenic Arabidopsis and tobacco plants. In transient assays with GFP and GUS reporter genes the At4g35985 promoter (P85) showed stronger expression (about 3.5 fold) compared to the At4g35987 promoter (P87). The tissue specific as well as stress responsive functional nature of the bidirectional promoter was evaluated in independent transgenic Arabidopsis and tobacco lines. Expression of P85 activity was detected in the midrib of leaves, leaf trichomes, apical meristemic regions, throughout the root, lateral roots and flowers. The expression of P87 was observed in leaf-tip, hydathodes, apical meristem, root tips, emerging lateral root tips, root stele region and in floral tissues. The bidirectional promoter in both orientations shows differential up-regulation (2.5 to 3 fold) under salt stress. Use of such regulatory elements of bidirectional promoters showing spatial and stress inducible promoter-functions in heterologous system might be an important tool for plant biotechnology and gene stacking applications. PMID:24260266

  3. An intergenic region shared by At4g35985 and At4g35987 in Arabidopsis thaliana is a tissue specific and stress inducible bidirectional promoter analyzed in transgenic arabidopsis and tobacco plants.

    Directory of Open Access Journals (Sweden)

    Joydeep Banerjee

    Full Text Available On chromosome 4 in the Arabidopsis genome, two neighboring genes (calmodulin methyl transferase At4g35987 and senescence associated gene At4g35985 are located in a head-to-head divergent orientation sharing a putative bidirectional promoter. This 1258 bp intergenic region contains a number of environmental stress responsive and tissue specific cis-regulatory elements. Transcript analysis of At4g35985 and At4g35987 genes by quantitative real time PCR showed tissue specific and stress inducible expression profiles. We tested the bidirectional promoter-function of the intergenic region shared by the divergent genes At4g35985 and At4g35987 using two reporter genes (GFP and GUS in both orientations in transient tobacco protoplast and Agro-infiltration assays, as well as in stably transformed transgenic Arabidopsis and tobacco plants. In transient assays with GFP and GUS reporter genes the At4g35985 promoter (P85 showed stronger expression (about 3.5 fold compared to the At4g35987 promoter (P87. The tissue specific as well as stress responsive functional nature of the bidirectional promoter was evaluated in independent transgenic Arabidopsis and tobacco lines. Expression of P85 activity was detected in the midrib of leaves, leaf trichomes, apical meristemic regions, throughout the root, lateral roots and flowers. The expression of P87 was observed in leaf-tip, hydathodes, apical meristem, root tips, emerging lateral root tips, root stele region and in floral tissues. The bidirectional promoter in both orientations shows differential up-regulation (2.5 to 3 fold under salt stress. Use of such regulatory elements of bidirectional promoters showing spatial and stress inducible promoter-functions in heterologous system might be an important tool for plant biotechnology and gene stacking applications.

  4. Analysis of ultra-deep pyrosequencing and cloning based sequencing of the basic core promoter/precore/core region of hepatitis B virus using newly developed bioinformatics tools.

    Directory of Open Access Journals (Sweden)

    Mukhlid Yousif

    Full Text Available AIMS: The aims of this study were to develop bioinformatics tools to explore ultra-deep pyrosequencing (UDPS data, to test these tools, and to use them to determine the optimum error threshold, and to compare results from UDPS and cloning based sequencing (CBS. METHODS: Four serum samples, infected with either genotype D or E, from HBeAg-positive and HBeAg-negative patients were randomly selected. UDPS and CBS were used to sequence the basic core promoter/precore region of HBV. Two online bioinformatics tools, the "Deep Threshold Tool" and the "Rosetta Tool" (http://hvdr.bioinf.wits.ac.za/tools/, were built to test and analyze the generated data. RESULTS: A total of 10952 reads were generated by UDPS on the 454 GS Junior platform. In the four samples, substitutions, detected at 0.5% threshold or above, were identified at 39 unique positions, 25 of which were non-synonymous mutations. Sample #2 (HBeAg-negative, genotype D had substitutions in 26 positions, followed by sample #1 (HBeAg-negative, genotype E in 12 positions, sample #3 (HBeAg-positive, genotype D in 7 positions and sample #4 (HBeAg-positive, genotype E in only four positions. The ratio of nucleotide substitutions between isolates from HBeAg-negative and HBeAg-positive patients was 3.5 ∶ 1. Compared to genotype E isolates, genotype D isolates showed greater variation in the X, basic core promoter/precore and core regions. Only 18 of the 39 positions identified by UDPS were detected by CBS, which detected 14 of the 25 non-synonymous mutations detected by UDPS. CONCLUSION: UDPS data should be approached with caution. Appropriate curation of read data is required prior to analysis, in order to clean the data and eliminate artefacts. CBS detected fewer than 50% of the substitutions detected by UDPS. Furthermore it is important that the appropriate consensus (reference sequence is used in order to identify variants correctly.

  5. The effect of metallothionein 2A core promoter region single-nucleotide polymorphism on accumulation of toxic metals in sinonasal inverted papilloma tissues

    Energy Technology Data Exchange (ETDEWEB)

    Starska, Katarzyna, E-mail: katarzyna.starska@umed.lodz.pl [I Department of Otolaryngology and Laryngological Oncology, Medical University of Łódź, Kopcinskiego 22, 90-153 Łódź (Poland); Bryś, Magdalena; Forma, Ewa [Department of Cytobiochemistry, University of Łódź, Pomorska 142/143, 90-236 Łódź (Poland); Olszewski, Jurek; Pietkiewicz, Piotr [II Department of Otolaryngology and Laryngological Oncology, Medical University of Łódź, Żeromskiego 113, 90-549 Łódź (Poland); Lewy-Trenda, Iwona; Danilewicz, Marian [Department of Pathology, Medical University of Łódź, Pomorska 251, 92-213 Łódź (Poland); Krześlak, Anna [Department of Cytobiochemistry, University of Łódź, Pomorska 142/143, 90-236 Łódź (Poland)

    2015-06-15

    Metallothioneins (MTs) are intracellular thiol-rich heavy metal-binding proteins which join trace metal ions protecting cells against heavy metal toxicity and regulate metal distribution and donation to various enzymes and transcription factors. The goal of this study was to identify the − 5 A/G (rs28366003) single-nucleotide polymorphism (SNP) in the core promoter region of the MT2A gene, and to investigate its effect on allele-specific gene expression and Cd, Zn, Cu and Ni content in sinonasal inverted papilloma tissue (IP), with non-cancerous sinonasal mucosa (NCM) as a control. The MT2A promoter region − 5 A/G SNP was identified by restriction fragment length polymorphism using 117 IP and 132 NCM. MT2A gene analysis was performed by quantitative real-time PCR. Metal levels were analyzed by flame atomic absorption spectrometry. The frequency of A allele carriage was 99.2% and 100% in IP and NCM, respectively. The G allele carriage was detected in 23.9% of IP and in 12.1% of the NCM samples. As a result, a significant association of − 5 A/G SNP in MT2A gene with mRNA expression in both groups was determined. A significant association was identified between the − 5 A/G SNP in the MT2A gene with mRNA expression in both groups. A highly significant association was detected between the rs28366003 genotype and Cd and Zn content in IP. Furthermore, significant differences were identified between A/A and A/G genotype with regard to the type of metal contaminant. The Spearman rank correlation results showed the MT2A gene expression and both Cd and Cu levels were negatively correlated. The results obtained in this study suggest that the − 5 A/G SNP in the MT2A gene may have an effect on allele-specific gene expression and toxic metal accumulation in sinonasal inverted papilloma. - Highlights: • MT2A gene expression and metal content in sinonasal inverted papilloma tissues • Association between SNP (rs28366003) and expression of MT2A • Significant

  6. Proximity to coast is linked to climate change belief.

    Science.gov (United States)

    Milfont, Taciano L; Evans, Laurel; Sibley, Chris G; Ries, Jan; Cunningham, Andrew

    2014-01-01

    Psychologists have examined the many psychological barriers to both climate change belief and concern. One barrier is the belief that climate change is too uncertain, and likely to happen in distant places and times, to people unlike oneself. Related to this perceived psychological distance of climate change, studies have shown that direct experience of the effects of climate change increases climate change concern. The present study examined the relationship between physical proximity to the coastline and climate change belief, as proximity may be related to experiencing or anticipating the effects of climate change such as sea-level rise. We show, in a national probability sample of 5,815 New Zealanders, that people living in closer proximity to the shoreline expressed greater belief that climate change is real and greater support for government regulation of carbon emissions. This proximity effect held when adjusting for height above sea level and regional poverty. The model also included individual differences in respondents' sex, age, education, political orientation, and wealth. The results indicate that physical place plays a role in the psychological acceptance of climate change, perhaps because the effects of climate change become more concrete and local.

  7. Proximity to coast is linked to climate change belief.

    Directory of Open Access Journals (Sweden)

    Taciano L Milfont

    Full Text Available Psychologists have examined the many psychological barriers to both climate change belief and concern. One barrier is the belief that climate change is too uncertain, and likely to happen in distant places and times, to people unlike oneself. Related to this perceived psychological distance of climate change, studies have shown that direct experience of the effects of climate change increases climate change concern. The present study examined the relationship between physical proximity to the coastline and climate change belief, as proximity may be related to experiencing or anticipating the effects of climate change such as sea-level rise. We show, in a national probability sample of 5,815 New Zealanders, that people living in closer proximity to the shoreline expressed greater belief that climate change is real and greater support for government regulation of carbon emissions. This proximity effect held when adjusting for height above sea level and regional poverty. The model also included individual differences in respondents' sex, age, education, political orientation, and wealth. The results indicate that physical place plays a role in the psychological acceptance of climate change, perhaps because the effects of climate change become more concrete and local.

  8. Functional outcome following proximal humeral interlocking system plating for displaced proximal humeral fractures

    OpenAIRE

    Thyagarajan David; Haridas Samarth; Jones Denise; Dent Colin; Evans Richard; Williams Rhys

    2009-01-01

    Aim: To assess the functional outcome following internal fixation with the PHILOS (proximal humeral interlocking system) for displaced proximal humeral fractures. Patients and Methods: We reviewed 30 consecutive patients treated surgically with the proximal humeral locking plate for a displaced proximal humeral fracture. Functional outcome was determined using the American Shoulder and Elbow Society (ASES) score and Constant Murley score. Results: Average age of the patients was 58 years...

  9. Best Proximity Points for a New Class of Generalized Proximal Mappings

    Directory of Open Access Journals (Sweden)

    Tayyab Kamran

    2017-03-01

    Full Text Available The best proximity points are usually used to find the optimal approximate solution of the operator equation Tx = x, when T has no fixed point. In this paper, we prove some best proximity point theorems for nonself multivalued operators, following the foot steps of Basha and Shahzad [Best proximity point theorems for generalized proximal contractions, Fixed Point Theory Appl., 2012, 2012:42].

  10. Preliminary phytochemical screening, proximate and elemental ...

    African Journals Online (AJOL)

    The seed powder of Moringa oleifera was analysed for its phytochemical, proximate and elemental composition using Folin-Denis spectrophotometric method, gravimetric method and energy dispersing X-ray fluorescence (EDXRF) transmission emission technique respectively. The seed powder had the following proximate ...

  11. Bimalleolar ankle fracture with proximal fibular fracture

    NARCIS (Netherlands)

    Colenbrander, R. J.; Struijs, P. A. A.; Ultee, J. M.

    2005-01-01

    A 56-year-old female patient suffered a bimalleolar ankle fracture with an additional proximal fibular fracture. This is an unusual fracture type, seldom reported in literature. It was operatively treated by open reduction and internal fixation of the lateral malleolar fracture. The proximal fibular

  12. Grouping by Proximity in Haptic Contour Detection

    Science.gov (United States)

    Overvliet, Krista E.; Krampe, Ralf Th.; Wagemans, Johan

    2013-01-01

    We investigated the applicability of the Gestalt principle of perceptual grouping by proximity in the haptic modality. To do so, we investigated the influence of element proximity on haptic contour detection. In the course of four sessions ten participants performed a haptic contour detection task in which they freely explored a haptic random dot display that contained a contour in 50% of the trials. A contour was defined by a higher density of elements (raised dots), relative to the background surface. Proximity of the contour elements as well as the average proximity of background elements was systematically varied. We hypothesized that if proximity of contour elements influences haptic contour detection, detection will be more likely when contour elements are in closer proximity. This should be irrespective of the ratio with the proximity of the background elements. Results showed indeed that the closer the contour elements were, the higher the detection rates. Moreover, this was the case independent of the contour/background ratio. We conclude that the Gestalt law of proximity applies to haptic contour detection. PMID:23762364

  13. Proximate analysis on four edible mushrooms ADEDAYO ...

    African Journals Online (AJOL)

    Michael Horsfall

    Vol. 15 (1) 9 - 11. Full-text Available Online at www.bioline.org.br/ja. Proximate analysis on four edible mushrooms. ADEDAYO, MAJEKODUNMI RACHEL. Nigerian Stored Product Research Institute, P.M.B.3032, Kano. ABSTRACT: Proximate study was conducted on four edible mushrooms commonly found in farmlands in.

  14. Proximate Sources of Collective Teacher Efficacy

    Science.gov (United States)

    Adams, Curt M.; Forsyth, Patrick B.

    2006-01-01

    Purpose: Recent scholarship has augmented Bandura's theory underlying efficacy formation by pointing to more proximate sources of efficacy information involved in forming collective teacher efficacy. These proximate sources of efficacy information theoretically shape a teacher's perception of the teaching context, operationalizing the difficulty…

  15. Phytochemical screening, proximate analysis and anticonvulsant ...

    African Journals Online (AJOL)

    Spigelia anthelmia is used traditionally in Southern Nigeria for the treatment of infant convulsion and epilepsy. This study investigated the phytochemical constituents, proximate analysis and anticonvulsant effect of the methanolic extract of Spigelia anthelmia. Phytochemical evaluation and proximate analysis was carried ...

  16. Polymorphisms in the promoter region of the bovine lactoferrin gene influence milk somatic cell score and milk production traits in Chinese Holstein cows.

    Science.gov (United States)

    Mao, Yongjiang; Zhu, Xiaorui; Xing, Shiyu; Zhang, Meirong; Zhang, Huimin; Wang, Xiaolong; Karrow, Niel; Yang, Liguo; Yang, Zhangping

    2015-12-01

    Lactoferrin is an iron-binding protein found in cow's milk that plays an important role in preventing mastitis caused by intramammary infection. In this study, 20 Chinese Holstein cows were selected randomly for PCR amplification and sequencing of the bovine lactoferrin gene promoter region and used for SNP discovery in the region between nucleotide positions -461 to -132. Three SNPs (-270T>C, -190G>A and -156A>G) were identified in bovine lactoferrin, then Chinese Holstein cows (n=866) were genotyped using Sequenom MassARRAY (Sequenom Inc., San Diego, CA) based on the previous SNP information in this study, and the associations between SNPs or haplotype and milk somatic cell score (SCS) and production traits were analyzed by the least squares method in the GLM procedure of SAS. SNPs -270T>C and -156A>G showed close linkage disequilibrium (r(2)=0.76). The SNP -190G>A showed a significant association with SCS, and individuals with genotype GG had higher SCS than genotypes AG and AA. Associations were found between the SNPs -270T>C and -190G>A with SCS and the milk composition. The software MatInspector revealed that these SNPs were located within several potential transcription factor binding sites, including NF-κB p50, KLF7 and SP1, and may alter gene expression, but further investigation will be required to elucidate the biological and practical relevance of these SNPs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Development of a Reverse Genetic System for Infectious Salmon Anemia Virus: Rescue of Recombinant Fluorescent Virus by Using Salmon Internal Transcribed Spacer Region 1 as a Novel Promoter

    Science.gov (United States)

    Toro-Ascuy, Daniela; Tambley, Carolina; Beltran, Carolina; Mascayano, Carolina; Sandoval, Nicolas; Olivares, Eduardo; Medina, Rafael A.; Spencer, Eugenio

    2014-01-01

    Infectious salmon anemia (ISA) is a serious disease of marine-farmed Atlantic salmon (Salmo salar) caused by ISA virus (ISAV), belonging to the genus Isavirus, family Orthomyxoviridae. There is an urgent need to understand the virulence factors and pathogenic mechanisms of ISAV and to develop new vaccine approaches. Using a recombinant molecular biology approach, we report the development of a plasmid-based reverse genetic system for ISAV, which includes the use of a novel fish promoter, the Atlantic salmon internal transcribed spacer region 1 (ITS-1). Salmon cells cotransfected with pSS-URG-based vectors expressing the eight viral RNA segments and four cytomegalovirus (CMV)-based vectors that express the four proteins of the ISAV ribonucleoprotein complex allowed the generation of infectious recombinant ISAV (rISAV). We generated three recombinant viruses, wild-type rISAV901_09 and rISAVrS6-NotI-HPR containing a NotI restriction site and rISAVS6/EGFP-HPR harboring the open reading frame of enhanced green fluorescent protein (EGFP), both within the highly polymorphic region (HPR) of segment 6. All rescued viruses showed replication activity and cytopathic effect in Atlantic salmon kidney-infected cells. The fluorescent recombinant viruses also showed a characteristic cytopathic effect in salmon cells, and the viruses replicated to a titer of 6.5 × 105 PFU/ml, similar to that of the wild-type virus. This novel reverse genetics system offers a powerful tool to study the molecular biology of ISAV and to develop a new generation of ISAV vaccines to prevent and mitigate ISAV infection, which has had a profound effect on the salmon industry. PMID:25480750

  18. Intramedullary compression device for proximal ulna fracture.

    Science.gov (United States)

    Hong, Choon Chiet; Han, Fucai; Decruz, Joshua; Pannirselvam, Vinodhkumar; Murphy, Diarmuid

    2015-02-01

    Proximal ulna fractures account for 20% of all proximal forearm fractures. Many treatment options are available for such fractures, such as cast immobilisation, plate and screw fixation, tension band wiring and intramedullary screw fixation, depending on the fracture pattern. Due to the subcutaneous nature of the proximal forearm, it is vulnerable to open injuries over the dorsal aspect of the proximal ulna. This may in turn prove challenging, as it is critical to obtain adequate soft tissue coverage to reduce the risk of implant exposure and bony infections. We herein describe a patient with a Gustillo III-B open fracture of the proximal ulna, treated with minimally invasive intramedullary screw fixation using a 6.0-mm cannulated headless titanium compression screw (FusiFIX, Péronnas, France).

  19. A review of 5-HT transporter linked promoter region (5-HTTLPR) polymorphism and associations with alcohol use problems and sexual risk behaviors.

    Science.gov (United States)

    Rubens, Muni; Ramamoorthy, Venkataraghavan; Attonito, Jennifer; Saxena, Anshul; Appunni, Sandeep; Shehadeh, Nancy; Dévieux, Jessy G

    2016-01-01

    Alcohol use and sexual risk behaviors are multidimensional phenomena involving many genetic and environmental factors. 5-HT transporter linked promoter region (5-HTTLPR) polymorphism constitutes an important factor affecting alcohol use problems and risky sexual behaviors. This paper narratively reviews studies on 5-HTTLPR polymorphism and its associations with alcohol use problems and sexual risk behaviors. We searched the electronic databases, PubMed, Ovid, and Google Scholar for articles using MeSH terms. Relevant articles were reviewed and eligible articles were selected for the study. Many studies have reported a significant but moderate association between 5-HTTLPR polymorphism and alcohol use problems. These studies have implicated the presence of at least one S allele to be associated with significant increases in alcohol use problems. Similarly, some studies associate the S allele with increased sexual risk behaviors. Effective alcohol cessation initiatives and STI/HIV prevention programs should be modified to account for 5-HTTLPR polymorphism before planning interventions; genetic effects could moderate the intervention effect.

  20. A multistakeholder platform to promote health and prevent noncommunicable diseases in the region of the Americas: the Pan American Health Organization partners forum for action.

    Science.gov (United States)

    Hospedales, C James; Jané-Llopis, Eva

    2011-08-01

    Noncommunicable diseases (NCDs) and obesity are the most serious health problem facing the countries of the Americas in terms of avoidable deaths as well as costs to governments, families, and business. The main causes are ageing of the population, and widespread risks such as tobacco use, unhealthy diet, physical inactivity, and harmful use of alcohol, linked to major changes in the way we live and work, to public policies, cultural norms, and private sector forces. Underlying determinants are globalization, urbanization, poverty, education, gender, ethnicity, and access to health services. Yet, approximately 80% of cardiovascular disease and diabetes, and 40% of cancer, are preventable through a range of cost-effective population and individual measures for those at high risk of living with NCDs. However, the multisectoral nature of NCDs requires a cross-sector response to succeed. Several governments have commenced intersectoral efforts, and civil society and private sector also have many initiatives, but the responses are fragmented and skewed. The Partners Forum is being launched by the Pan American Health Organization in collaboration with the World Economic Forum and a set of partners including member states, partners in civil society, and partners in the private sector, as a multisector platform to catalyze, recognize, and scale up collaborative action to promote health and prevent and control NCDs at regional, subregional, and country level. The principles of partnership and lessons learned from other partnership experiences are being used in its design.

  1. Site-directed mutagenesis of the -10 region of the lacUV5 promoter. Introduction of dA4.dT4 tract suppresses open complex formation.

    Science.gov (United States)

    Chan, P T; Lebowitz, J

    1990-03-05

    Homopolymeric dAn.dTn sequences, where n is 4 or greater, have special properties leading to increased duplex stability and DNA bending. The lacUV5 promoter was used to examine the functional consequences of changing the -10 TATAAT consensus sequence to the sequence TAAAAT. The transversion mutation at the underlined site was accomplished with site-directed mutagenesis using translation termination as the selection procedure. For free DNA, structural differences at the 5' and 3' junction regions of the dA4.dT4 tract can be readily detected by DNase I digestion. However, site binding by Escherichia coli RNA polymerase appeared unaltered by the TAAAAT sequence since identical DNase I footprints were obtained for the lacUV5 and mutant promoters. Binding competition studies under different ionic strengths revealed a significant reduction in mutant promoter open complex formation relative to the lacUV5 promoter. Mutant promoter open complexes also dissociated faster and to a greater extent than the corresponding lacUV5 promoter open complexes when challenged with heparin or a combination of heparin and increased KCl concentration. Consequently, mutant promoter open complexes appear less stable than lacUV5 promoter open complexes.

  2. Understanding, promoting and protecting geodiversity and geoheritage of the Piemonte region (Italy) through innovative techniques and public engagement in Earth Science studies

    Science.gov (United States)

    Giardino, Marco; Lozar, Francesca; Perotti, Luigi; Palomba, Mauro; Groppo, Chiara; Natalicchio, Marcello; Ghiraldi, Luca; Beltramo, Riccardo; Lombardo, Vincenzo

    2016-04-01

    The onset of Antropocene demonstrates the importance of considering both 1) geodiversity and 2) geoheritage as parts of the landscape "interfaces" where relationships between natural and socio-economic systems can be studied and interpreted. By definition: 1) is the variety, recognizable in nature ("diversity"), of geological features (rocks, minerals, fossils…), of geomorphological environments (and related forms and processes) and of soil characteristics; 2) is an integral part of the global natural heritage focusing on unique, special and representative sites of geological interests (geosites l.s.). In the Antropocene, both 1) and 2) hold a dynamic character, as the result of actions and interactions of natural and/or human factors. Therefore, geodiversity and geoheritage studies are essential for breaking down geological environments and human territories into their main parts and to understand the variables and mechanisms that control their changes. In this perspective, results of the multidisciplinary project PROGEO-Piemonte ("PROactive management of GEOlogical heritage in the Piemonte Region") are presented here: an innovative approach for assessing geodiversity in order to select areas of high potential value of geoheritage to be enhanced by targeted management actions. Since the geodiversity of Piemonte is materialized by elements of high scientific, educational, tourism, etc. value, the geosites where this geoheritage is preserved have been comprehensively analysed and characterized for encompassing both public and private interests. 9 strategic geothematic areas have been selected in the Piemonte Region to test this approach, and to improve social engagement aimed at protecting and promoting geodiversity ad geoheritage. The investigated areas represent the multifaceted geodiversity of Piemonte; each area is characterized by high potential for scientific studies, enhancement of public understanding of science, recreation activities and for economic

  3. Perceptions of health promoters about health promotion ...

    African Journals Online (AJOL)

    Perceptions of health promoters about health promotion programmes for families with adolescents orphaned as a result of AIDS in the rural Hammanskraal region in ... education by using the community and national media, providing information material and providing access to the internet in order to allow more people, ...

  4. Proximal Alternating Direction Method with Relaxed Proximal Parameters for the Least Squares Covariance Adjustment Problem

    Directory of Open Access Journals (Sweden)

    Minghua Xu

    2014-01-01

    Full Text Available We consider the problem of seeking a symmetric positive semidefinite matrix in a closed convex set to approximate a given matrix. This problem may arise in several areas of numerical linear algebra or come from finance industry or statistics and thus has many applications. For solving this class of matrix optimization problems, many methods have been proposed in the literature. The proximal alternating direction method is one of those methods which can be easily applied to solve these matrix optimization problems. Generally, the proximal parameters of the proximal alternating direction method are greater than zero. In this paper, we conclude that the restriction on the proximal parameters can be relaxed for solving this kind of matrix optimization problems. Numerical experiments also show that the proximal alternating direction method with the relaxed proximal parameters is convergent and generally has a better performance than the classical proximal alternating direction method.

  5. A novel tumor-promoting function residing in the 5' non-coding region of vascular endothelial growth factor mRNA.

    Directory of Open Access Journals (Sweden)

    Kiyoshi Masuda

    2008-05-01

    Full Text Available BACKGROUND: Vascular endothelial growth factor-A (VEGF is one of the key regulators of tumor development, hence it is considered to be an important therapeutic target for cancer treatment. However, clinical trials have suggested that anti-VEGF monotherapy was less effective than standard chemotherapy. On the basis of the evidence, we hypothesized that vegf mRNA may have unrecognized function(s in cancer cells. METHODS AND FINDINGS: Knockdown of VEGF with vegf-targeting small-interfering (si RNAs increased susceptibility of human colon cancer cell line (HCT116 to apoptosis caused with 5-fluorouracil, etoposide, or doxorubicin. Recombinant human VEGF165 did not completely inhibit this apoptosis. Conversely, overexpression of VEGF165 increased resistance to anti-cancer drug-induced apoptosis, while an anti-VEGF165-neutralizing antibody did not completely block the resistance. We prepared plasmids encoding full-length vegf mRNA with mutation of signal sequence, vegf mRNAs lacking untranslated regions (UTRs, or mutated 5'UTRs. Using these plasmids, we revealed that the 5'UTR of vegf mRNA possessed anti-apoptotic activity. The 5'UTR-mediated activity was not affected by a protein synthesis inhibitor, cycloheximide. We established HCT116 clones stably expressing either the vegf 5'UTR or the mutated 5'UTR. The clones expressing the 5'UTR, but not the mutated one, showed increased anchorage-independent growth in vitro and formed progressive tumors when implanted in athymic nude mice. Microarray and quantitative real-time PCR analyses indicated that the vegf 5'UTR-expressing tumors had up-regulated anti-apoptotic genes, multidrug-resistant genes, and growth-promoting genes, while pro-apoptotic genes were down-regulated. Notably, expression of signal transducers and activators of transcription 1 (STAT1 was markedly repressed in the 5'UTR-expressing tumors, resulting in down-regulation of a STAT1-responsive cluster of genes (43 genes. As a result, the

  6. The Life Saving Effects of Hospital Proximity

    DEFF Research Database (Denmark)

    Bertoli, Paola; Grembi, Veronica

    We assess the lifesaving effect of hospital proximity using data on fatality rates of road-traffic accidents. While most of the literature on this topic is based on changes in distance to the nearest hospital triggered by hospital closures and use OLS estimates, our identification comes from......) increases the fatality rate by 13.84% on the sample average. This is equal to a 0.92 additional death per every 100 accidents. We show that OLS estimates provide a downward biased measure of the real effect of hospital proximity because they do not fully solve spatial sorting problems. Proximity matters...

  7. Copper in silicon: Quantitative analysis of internal and proximity gettering

    Energy Technology Data Exchange (ETDEWEB)

    McHugo, S.A. [Lawrence Berkeley National Lab., CA (United States); Flink, C.; Weber, E.R. [Univ. of California, Berkeley, CA (United States)] [and others

    1997-08-01

    The behavior of copper in the presence of a proximity gettering mechanism and a standard internal gettering mechanism in silicon was studied. He implantation-induced cavities in the near surface region were used as a proximity gettering mechanism and oxygen precipitates in the bulk of the material provided internal gettering sites. Moderate levels of copper contamination were introduced by ion implantation such that the copper was not supersaturated during the anneals, thus providing realistic copper contamination/gettering conditions. Copper concentrations at cavities and internal gettering sites were quantitatively measured after the annealings. In this manner, the gettering effectiveness of cavities was measured when in direct competition with internal gettering sites. The cavities were found to be the dominant gettering mechanism with only a small amount of copper gettered at the internal gettering sites. These results reveal the benefits of a segregation-type gettering mechanism for typical contamination conditions.

  8. Proximal Multitask Learning Over Networks With Sparsity-Inducing Coregularization

    Science.gov (United States)

    Nassif, Roula; Richard, Cedric; Ferrari, Andre; Sayed, Ali H.

    2016-12-01

    In this work, we consider multitask learning problems where clusters of nodes are interested in estimating their own parameter vector. Cooperation among clusters is beneficial when the optimal models of adjacent clusters have a good number of similar entries. We propose a fully distributed algorithm for solving this problem. The approach relies on minimizing a global mean-square error criterion regularized by non-differentiable terms to promote cooperation among neighboring clusters. A general diffusion forward-backward splitting strategy is introduced. Then, it is specialized to the case of sparsity promoting regularizers. A closed-form expression for the proximal operator of a weighted sum of $\\ell_1$-norms is derived to achieve higher efficiency. We also provide conditions on the step-sizes that ensure convergence of the algorithm in the mean and mean-square error sense. Simulations are conducted to illustrate the effectiveness of the strategy.

  9. A novel assay for detecting the mutation of nucleotide 1758-1777 deletion in core promoter region of hepatitis B virus

    Directory of Open Access Journals (Sweden)

    Xue-yuan NIAN

    2016-04-01

    Full Text Available Objective  Nucleotide (nt 1758-1777 deletion in core promoter (CP region of hepatitis B virus (HBV has been suggested to be associated with disease progression. However, the complicated and less sensitive assay for it limited its use in clinic. The present study was aimed at setting a novel assay for its detection using single-tube nested PCR amplification and real-time PCR melting curve analysis. Methods  The PCR primers were designed through analysis of HBV genomic sequences in GenBank, and detection conditions were optimized. HBV CP region from 340 serum samples of chronic hepatitis B patients were amplified and directly sequenced, and fifty samples were randomly selected for cloning and sequencing for analysis of nt 1758-1777 deletion. The wild-type and deletion-type plasmids were extracted from mono-cloning samples. Positive standard of melting curve analysis was set up in light of the results of PCR amplification of two standard plasmids and cloning samples. The new method of assay was used in 340 samples, and the data were verified by the results of pyrosequencing. Results  Sixteen (4.7% samples were positive for the deletion by direct sequencing, and no less than 15% samples in standard plasmids and cloning sequencing showed sequence deletion. The melting temperature (Tm of deletion-type plasmid and cloning samples containing ≥15% proportion of the deletion sequence was ≥88.3℃, which was determined as positive standard of the novel assay. Forty-seven (13.8% samples were detected positive for nt 1758-1777 deletion by the novel assay. Among them, deletion ratio was ≥1.0% in 38 samples and <1.0% in 9 samples by pyrosequencing, respectively. The deletion ratio was all <1.0% in 15 negative control samples. The deletion ratio of 1.0% was taken as positive cutoff by pyrosequencing, the novel assay had 80.9% positive consistency and 100% negative consistency, with a Kappa value of 0.671. Conclusions Comparing with direct

  10. Wake-promoting actions of median nerve stimulation in TBI-induced coma: An investigation of orexin-A and orexin receptor 1 in the hypothalamic region.

    Science.gov (United States)

    Zhong, Ying-Jun; Feng, Zhen; Wang, Liang; Wei, Tian-Qi

    2015-09-01

    A coma is a serious complication, which can occur following traumatic brain injury (TBI), for which no effective treatment has been established. Previous studies have suggested that neural electrical stimulation, including median nerve stimulation (MNS), may be an effective method for treating patients in a coma, and orexin‑A, an excitatory hypothalamic neuropeptide, may be involved in wakefulness. However, the exact mechanisms underlying this involvement remain to be elucidated. The present study aimed to examine the arousal‑promoting role of MNS in rats in a TBI‑induced coma and to investigate the potential mechanisms involved. A total of 90 rats were divided into three groups, comprising a control group, sham‑stimulated (TBI) group and a stimulated (TBI + MNS) group. MNS was performed on the animals, which were in a TBI‑induced comatose state. Changes in the behavior of the rats were observed following MNS. Subsequently, hypothalamic tissues were extracted from the rats 6, 12 and 24 h following TBI or MNS, respectively. The expression levels of orexin‑A and orexin receptor‑1 (OX1R) in the hypothalamus were examined using immunohistochemistry, western blotting and an enzyme‑linked immunosorbent assay. The results demonstrated that 21 rats subjected to TBI‑induced coma exhibited a restored righting reflex and response to pain stimuli following MNS. In addition, ignificant differences in the expression levels of orexin‑A and OXIR were observed among the three groups and among the time‑points. Orexin‑A and OX1R were upregulated following MNS. The rats in the stimulated group reacted to the MNS and exhibited a re‑awakening response. The results of the present study indicated that MNS may be a therapeutic option for TBI‑induced coma. The mechanism may be associated with increasing expression levels of the excitatory hypothalamic neuropeptide, orexin-A, and its receptor, OX1R, in the hypothalamic region.

  11. Prevalence of genetic polymorphisms in the promoter region of the alpha-1 antitrypsin (SERPINA1 gene in chronic liver disease: a case control study

    Directory of Open Access Journals (Sweden)

    van Oijen Martijn GH

    2010-02-01

    Full Text Available Abstract Background Alpha-1 antitrypsin (A1AT deficiency, caused by the Z allele (p.E342K and S allele (p.E264V in the SERPINA1 gene, can induce liver and pulmonary disease. Different mechanisms appear to be responsible for the pathogenesis of these divergent disease expressions. The c.-1973T >C polymorphism located in the SERPINA1 promoter region is found more frequent in A1AT deficiency patients with liver disease compared to patients with pulmonary disease, but data are lacking regarding contribution to the development of liver diseases caused by other aetiologies. Aim To study the prevalence of c.-1973T >C, Z allele and S allele in a cohort of patients with liver disease of various aetiologies compared with healthy controls and to evaluate its effect on disease progression. Methods A total of 297 patients with liver disease from various aetiologies and 297 age and gender matched healthy controls were included. The c.-1973T >C polymorphism and Z and S alleles of the SERPINA1 gene were analyzed by real-time PCR. Results c.-1973T >C was similarly distributed between patients with liver disease of various origins and healthy controls. Furthermore, the distribution of c.-1973T >C was independent from aetiology subgroup. In patients with liver disease mean ages at of onset of liver disease were 44.4, 42.3 and 40.7 years for the c.-1973 T/T, T/C and C/C genotype respectively (NS. S allele heterozygosity was increased in patients with drug induced liver injury (DILI, (OR 4.3; 95%CI 1.1-17.2. Conclusion In our study, c.-1973T >C polymorphism was not a risk factor for liver disease of various aetiologies. In addition, S allele heterozygosity might contribute to the development of DILI.

  12. Prevalence of genetic polymorphisms in the promoter region of the alpha-1 antitrypsin (SERPINA1) gene in chronic liver disease: a case control study.

    Science.gov (United States)

    Kok, Karin F; te Morsche, René H; van Oijen, Martijn G H; Drenth, Joost P H

    2010-02-20

    Alpha-1 antitrypsin (A1AT) deficiency, caused by the Z allele (p.E342K) and S allele (p.E264V) in the SERPINA1 gene, can induce liver and pulmonary disease. Different mechanisms appear to be responsible for the pathogenesis of these divergent disease expressions. The c.-1973T >C polymorphism located in the SERPINA1 promoter region is found more frequent in A1AT deficiency patients with liver disease compared to patients with pulmonary disease, but data are lacking regarding contribution to the development of liver diseases caused by other aetiologies. To study the prevalence of c.-1973T >C, Z allele and S allele in a cohort of patients with liver disease of various aetiologies compared with healthy controls and to evaluate its effect on disease progression. A total of 297 patients with liver disease from various aetiologies and 297 age and gender matched healthy controls were included. The c.-1973T >C polymorphism and Z and S alleles of the SERPINA1 gene were analyzed by real-time PCR. c.-1973T >C was similarly distributed between patients with liver disease of various origins and healthy controls. Furthermore, the distribution of c.-1973T >C was independent from aetiology subgroup. In patients with liver disease mean ages at of onset of liver disease were 44.4, 42.3 and 40.7 years for the c.-1973 T/T, T/C and C/C genotype respectively (NS). S allele heterozygosity was increased in patients with drug induced liver injury (DILI), (OR 4.3; 95%CI 1.1-17.2). In our study, c.-1973T >C polymorphism was not a risk factor for liver disease of various aetiologies. In addition, S allele heterozygosity might contribute to the development of DILI.

  13. Comparative analysis of the mammalian WNT4 promoter

    Directory of Open Access Journals (Sweden)

    Shaw Geoffrey

    2009-09-01

    Full Text Available Abstract Background WNT4 is a critical signalling molecule in embryogenesis and homeostasis, but the elements that control its transcriptional regulation are largely unknown. This study uses comparative cross species sequence and functional analyses between humans and a marsupial (the tammar wallaby,Macropus eugenii to refine the mammalian Wnt4 promoter. Results We have defined a highly conserved 89 bp minimal promoter region in human WNT4 by comparative analysis with the tammar wallaby. There are many conserved transcription factor binding sites in the proximal promoter region, including SP1, MyoD, NFκB and AP2, as well as highly conserved CpG islands within the human, mouse and marsupial promoters, suggesting that DNA methylation may play an important role in WNT4 transcriptional regulation. Conclusion Using a marsupial model, we have been able to provide new information on the transcriptional regulators in the promoter of this essential mammalian developmental gene, WNT4. These transcription factor binding sites and CpG islands are highly conserved in two disparate mammals, and are likely key controlling elements in the regulation of this essential developmental gene.

  14. The Effect of Cement Placement on Augmentation of the Osteoporotic Proximal Femur

    OpenAIRE

    Sutter, Edward G.; Wall, Simon J.; Mears, Simon C; Belkoff, Stephen M.

    2010-01-01

    Femoroplasty, the augmentation of the proximal femur, has been shown in biomechanical studies to increase the energy required to produce a fracture and therefore may reduce the risk of such injuries. The purpose of our study was to test the hypotheses that: (1) 15 mL of cement was sufficient to mechanically augment the proximal femur, (2) there was no difference in augmentation effect between cement placement in the intertrochanteric region and in the femoral neck, and (3) cement placement in...

  15. Does Proximity Matter for Knowledge Transfer from Public Institutes and Universities to Firms?

    OpenAIRE

    Anthony Arundel; Aldo Geuna

    2001-01-01

    'National Innovation Systems' theories are built upon the assumption that linkages among organisations matter to innovation. Specifically, proximity is a crucial factor in most of the explanations of regional innovation systems. Yet several thing, such as the rapid growth of the internet and email, suggest that the role of proximity could be breaking down, particularly for large firms with the financial resources to seek out knowledge anywhere in the world.However, the need to access tacit kn...

  16. Regulatory Focus, Proximity to Goal Weight, and Weight Loss Maintenance.

    Science.gov (United States)

    Fuglestad, Paul T; Rothman, Alexander J; Jeffery, Robert W; Sherwood, Nancy E

    2015-09-01

    Regulatory focus theory proposes 2 self-regulatory orientations: promotion focus - related to achieving aspirations and positive outcomes - and prevention focus - related to fulfilling responsibilities and preventing negative outcomes. The investigation examined whether regulatory focus and proximity to goal weight moderated the effectiveness of a weight-loss maintenance intervention. Participants who lost ≥10% of their weight were assigned to guided or self-directed treatments and completed regulatory focus and weight goal measures. Across treatment groups, people who were more promotion-focused had better 2-year maintenance rates (defined as regain focused, especially if far from their goal weight (.59 versus .44). In the guided group, people who were more prevention-focused had better maintenance rates than people who were less prevention-focused if closer to their goal weight (.69 versus .42), but poorer maintenance rates if farther from their goal (.36 versus .72). In the self-directed group, prevention focus was unrelated to maintenance. Regulatory focus and proximity to goal weight moderated intervention effectiveness. Maintenance may be enhanced by tailoring treatments to regulatory focus and goal weight (eg, prevention-focused people far from their goals may need extra weight-loss support before focusing on maintenance).

  17. Proximity and Collaboration in European Nanotechnology

    NARCIS (Netherlands)

    Cunningham, S.W.; Werker, C.

    2011-01-01

    Collaborations are particularly important for the development and deployment of technology. We analyze the influence of organizational, technological and geographical proximity on European nanotechnology collaborations with the help of a publication dataset and additional geographical information.

  18. Ammonia transport in the proximal tubule.

    Science.gov (United States)

    Hamm, L L; Simon, E E

    1990-01-01

    The transport of ammonia in the proximal tubule is a complex interaction of a number of processes. Ammonia transport in the proximal tubule is clearly bidirectional; ammonia is secreted into the early proximal tubule lumen, but later in the proximal tubule, efflux out of the lumen may result in net ammonia reabsorption. Two mechanisms of ammonia transport have clearly been established: NH3 diffusion and NH4+ transport on the Na(+)-H+ exchanger. The relative contribution of these pathways to ammonia transport is still unsettled. Other pathways for ammonia transport, particularly NH4+ efflux out of the lumen, may be important as well. A variety of factors may modulate ammonia transport: plasma, cell and luminal pH, luminal flow rate, luminal potassium, and angiotensin II. Each of these factors also alters ammonia production rates and in most circumstances, ammonia transport appears to follow ammonia production rates.

  19. Proximate composition and cholesterol concentrations of ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-05-18

    DWB) for raw and fried samples, respectively, but decreased to 295.20 ... Key words: Rhynchophorus phoenicis, Oryctes monoceros, proximate composition, cholesterol, heat treatment. INTRODUCTION. Insects have played ...

  20. COMPARATIVE ANALYSIS OF PROXIMATE COMPOSITIONS OF ...

    African Journals Online (AJOL)

    Babatunde Emmanuel

    2011-10-06

    Oct 6, 2011 ... Fish allows for protein improved nutrition in that it has a high biological value in terms of high ... marine algae upon which the fish feed [11]. ... Proximate composition of catfish Clarias gariepinus and Tarpon atlanticus were.

  1. An upstream regulatory element confers orientation-independent enhancement of the TSG101 promoter activity in transformed cells.

    Science.gov (United States)

    Hsu, Shih-Fang; Goan, Yih-Gang; Tsai, Hsien-Yu; Lin, Yi-Ru; Liu, Rue-Tsuan; Cheng, Jiin-Tsuey

    2012-01-01

    Tumor susceptibility gene 101 (TSG101), a mammalian homologue of yeast vps23, is involved in protein sorting, vesicular trafficking and maintenance of genomic integrity. Upregulation of the TSG101 gene was found in human thyroid papillary and breast tumors. Here, we define the proximal promoter of human TSG101 at -1 to -436 by reporter assay. Intact Sp1 and MAZ binding sequences within this region are essential, and mutation of both sites eliminates proximal promoter activity implying cooperation between these two cis-elements. Chromatin immunoprecipitation and DNA affinity precipitation assay confirmed in vivo Sp1 binding on the GGGGCGGGTT sequence. MAZ protein was essential for TSG101 promoter activity because its knockdown using siRNA decreased reporter activity. An upstream regulatory element (URE) at the -1280 to -1757 region was identified to confer the orientation-independent enhancement of the promoter activity in transformed COS-1, ARO and WRO cell lines but not in a normal thyroid FRTL cell line. The sequence of this URE region contains putative binding sites for thyroid transcription factor 2 (TTF-2) and thyroid hormone receptor (T3R), which might be relevant to differential regulation of TSG101 promoter activity in transformed and primary cells.

  2. Phytochemical screening, proximate analysis and acute toxicity ...

    African Journals Online (AJOL)

    Phytochemical screening, proximate analysis and acute toxicity studies were carried out on the leaf extract of Cola lepidota, in accordance with established standard procedures. The proximate analysis reveals a moisture content of 27.43 ± 3.11 % w/w, total ash value 9.32 ± 0.27 % w/w, acid insoluble ash 3.12 ± 1.05 % w/w ...

  3. Proximate, Mineral and Phytochemical Composition of Dioscorea ...

    African Journals Online (AJOL)

    ADOWIE PERE

    ABSTRACT: Proximate, mineral and phytochemical composition of Dioscorea dumetorum tubers was investigated using standard procedures. Proximate analysis included in g% dry weight: crude protein (6.44 ± 0.32), crude fat (0.75 ± 0.04), crude fibre (15.00 ± 0.56), total ash. (3.45 ± 0.20) and a moisture content of 70.04 ...

  4. Painful Spastic Hip Dislocation: Proximal Femoral Resection

    OpenAIRE

    Albiñana, Javier; Gonzalez-Moran, Gaspar

    2002-01-01

    The dislocated hip in a non-ambulatory child with spastic paresis tends to be a painful interference to sleep, sitting upright, and perineal care. Proximal femoral resection-interposition arthroplasty is one method of treatment for this condition. We reviewed eight hips, two bilateral cases, with a mean follow-up of 30 months. Clinical improvement was observed in all except one case, with respect to pain relief and sitting tolerance. Some proximal migration was observed in three cases, despit...

  5. Promoting the health of Europeans in a rapidly changing world: a historical study of the implementation of World Health Organisation policies by the Nursing and Midwifery Unit, European Regional Office, 1970-2003

    DEFF Research Database (Denmark)

    Hallett, Christine; Wagner, Lis

    2011-01-01

    HALLETT C and WAGNER L. Nursing Inquiry 2011; 18: 359-368 Promoting the health of Europeans in a rapidly changing world: a historical study of the implementation of World Health Organisation policies by the Nursing and Midwifery Unit, European Regional Office, 1970-2003 The World Health Organisat......HALLETT C and WAGNER L. Nursing Inquiry 2011; 18: 359-368 Promoting the health of Europeans in a rapidly changing world: a historical study of the implementation of World Health Organisation policies by the Nursing and Midwifery Unit, European Regional Office, 1970-2003 The World Health...... Organisation (WHO) was inaugurated in 1948. Formed in a period of post-war devastation, WHO aimed to develop and meet goals that would rebuild the health of shattered populations. The historical study reported here examined the work of the Nursing and Midwifery Unit (NMU) of WHO's European Regional Office...

  6. Proximity sensor system development. CRADA final report

    Energy Technology Data Exchange (ETDEWEB)

    Haley, D.C. [Oak Ridge National Lab., TN (United States); Pigoski, T.M. [Merrit Systems, Inc. (United States)

    1998-01-01

    Lockheed Martin Energy Research Corporation (LMERC) and Merritt Systems, Inc. (MSI) entered into a Cooperative Research and Development Agreement (CRADA) for the development and demonstration of a compact, modular proximity sensing system suitable for application to a wide class of manipulator systems operated in support of environmental restoration and waste management activities. In teleoperated modes, proximity sensing provides the manipulator operator continuous information regarding the proximity of the manipulator to objects in the workspace. In teleoperated and robotic modes, proximity sensing provides added safety through the implementation of active whole arm collision avoidance capabilities. Oak Ridge National Laboratory (ORNL), managed by LMERC for the United States Department of Energy (DOE), has developed an application specific integrated circuit (ASIC) design for the electronics required to support a modular whole arm proximity sensing system based on the use of capacitive sensors developed at Sandia National Laboratories. The use of ASIC technology greatly reduces the size of the electronics required to support the selected sensor types allowing deployment of many small sensor nodes over a large area of the manipulator surface to provide maximum sensor coverage. The ASIC design also provides a communication interface to support sensor commands from and sensor data transmission to a distributed processing system which allows modular implementation and operation of the sensor system. MSI is a commercial small business specializing in proximity sensing systems based upon infrared and acoustic sensors.

  7. Transformations through Proximity Flying: A Phenomenological Investigation

    Science.gov (United States)

    Holmbom, Maria; Brymer, Eric; Schweitzer, Robert D.

    2017-01-01

    Participation in extreme sports has been linked to personal transformations in everyday life. Descriptions of lived experience resulting from transformative experiences are limited. Proximity flying, a relatively new discipline involving BASE jumping with a wingsuit where participants fly close to solid structures, is arguably one of the most extreme of extreme sports. The aim of this paper, part of a larger phenomenological study on the lived experience of proximity flying, is to explicate the ways in which participating in proximity flying influences the everyday lives of participants. Interpretative phenomenological analysis was used to explicate the lived experience of six proximity pilots. An analysis of interview transcripts revealed three significant themes describing the lived experience of participants. First, experiences of change were described as positive and skills developed through proximity flying were transferable into everyday life. Second, transformative experiences were considered fundamental to participants’ perspectives on life. Third, experience of transformation influenced their sense of personal identity and facilitated flourishing in other aspects of everyday life. Participants were clear that their experiences in proximity flying facilitated a profound process of transformation which manifest as changes in everyday capabilities and behaviors, values and sense of identity. PMID:29104552

  8. Adult and Child Development in the Zone of Proximal Development: Socratic Dialogue in a Playworld

    Science.gov (United States)

    Ferholt, Beth; Lecusay, Robert

    2010-01-01

    This article analyses adult and child development in the zone of proximal development in an educational practice based in Vygotsky's theories of play: the playworld educational practice. The playworld educational practice is a central component of a Scandinavian play pedagogy that promotes shared responsibility amongst adults and children for…

  9. Treatment of three- and four-part proximal humeral fractures with locking proximal humerus plate.

    Science.gov (United States)

    Sun, Jing-Cheng; Li, Yu-Lin; Ning, Guang-Zhi; Wu, Qiang; Feng, Shi-Qing

    2013-08-01

    The purpose of this study was to evaluate the effectiveness and complications of the locking proximal humerus plate to treat proximal humerus fractures. A retrospective clinical trial. Department of Orthopaedics, Tianjin Medical University General Hospital. Sixty-eight consecutive patients with three- or four-part fractures of the proximal humerus were treated with locking proximal humerus plates. The deltopectoral anterolateral acromial approach was used to the proximal humerus; open reduction and locking proximal humerus plate were applied. Constant Score was used to measure the shoulder functional recovery, and Visual Analog Scale (VAS) was used to measure subjective evaluation of pain. The radiology was observed. After average 26.7 months, the average Constant Score was 72.6 ± 13.2 points and the average VAS was 1.2 ± 0.8 points. All the complications such as screw perforation into the glenohumeral joint, screws loosening, soft tissue infections, avascular necrosis and delayed union occurred in eight cases (11.8 %). The effectiveness of the locking proximal humerus plate was similar to other published literatures on treating fractures of the proximal humerus; however, a lower complications rate in short follow-up time was observed in this study. It may potentially provide a favorable option for treating three- or four-part fractures of the proximal humerus. Dealing with each particular fracture pattern, surgeons should have a decision of appropriate way to internal fixation.

  10. Functional regions of HpaXm as elicitors with specific heat tolerance induce the hypersensitive response or plant growth promotion in nonhost plants.

    Science.gov (United States)

    Liu, Yue; Zhou, Xiaoyun; Liu, Wenbo; Xiong, Xiaohui; Lv, Chuyang; Zhou, Xiang; Miao, Weiguo

    2018-01-01

    HpaXm produced by the cotton leaf blight bacterium Xanthomonas citri subsp. malvacearum is a novel harpin elicitor of the induced hypersensitive response (HR) in tobacco. We investigated whether fragments of HpaXm, compared with fragments of Hpa1Xoo, are sufficient for HR or plant growth promotion (PGP) elicitation using four synthetic peptides (HpaXm35-51, HpaXm10-39, Hpa1Xoo36-52 and Hpa1Xoo10-40). We also heated the fragments to determine the heat tolerance of the functional fragments. HpaXm35-51 and Hpa1Xoo36-52 induced hypersensitive response (HR). Bursts of reactive oxygen intermediates (ROI) induced by HpaXm35-51 and Hpa1Xoo36-52 were earlier and stronger than those induced by HpaXm and Hpa1Xoo. In plants treated with HpaXm35-51 or Hpa1Xoo36-52, the expression of the HR marker genes Hin1 and Hsr203J and the active oxygen metabolism related gene AOX were significantly upregulated. These findings suggest that the predicted α-helical structures of the HpaXm35-51 and Hpa1Xoo36-52 fragments are crucial for HR. PGP result by soaking seeds in unheated/heated HpaXm10-39 or Hpa1Xoo10-40 solution prior to transfer, which obviously enhances root growth and the aerial parts of plants. The PGP related gene NtEXP6 was greatly enhanced when plants were sprayed with a solution of HpaXm10-39 or Hpa1Xoo10-40; heated fragment treatments induced higher levels of NtEXP6 expression than unheated HpaXm fragments. In addition, HR marker genes induced by the heated fragments had lower expression levels than when induced with unheated HpaXm fragments. Moreover, the expression levels of HR marker genes and PGP related genes induced by treatment with Hpa1Xoo fragments before or after heating were the opposite of those induced by HpaXm fragments. Different functional fragments of harpin and different harpins with the same functional region have different degrees of heat tolerance. Therefore, the heat resistance of harpin is conservative, but the degree of heat tolerance of the

  11. Polymorphism of the DQA1 promoter region (QAP) and DRB1, QAP, DQA1, DQB1 haplotypes in systemic lupus erythematosus. SLE Study Group members.

    Science.gov (United States)

    Yao, Z; Kimura, A; Hartung, K; Haas, P J; Volgger, A; Brünnler, G; Bönisch, J; Albert, E D

    1993-01-01

    We have investigated the DNA polymorphism for the DQA1 promoter region (QAP) and HLA-class II DRB1, DQA1, and DQB1 genes in 178 central European patients with Systemic lupus erythematosus (SLE) using polymerase chain reaction and Dig-ddUTP labeled oligonucleotides. Increased frequencies of DRB1*02 and *03 are confirmed by DNA typing. In addition, the frequencies of DQA1*0501, *0102 and DQB1*0201, *0602 alleles are increased in the patients as compared to controls. The strongest association to SLE is found with DRB1*03 and DOB1*0201 alleles (p QAP variants. Increased frequencies of QAP1.2 and QAP4.1 are observed in patients as compared to controls (p QAP variants and DQA1, DRB1 alleles. Certain QAP variants are completely associated with DQA1 and DRB1 alleles, whereas others can combine with different DQA1 and DRB1 alleles. All DRB1*02-positive patients and controls carry QAP1.2, and all DRB1*03-positive patients and controls carry QAP4.1. Conversely, the QAP1.2 variant appears only in DRB1*02 haplotypes, while the QAP4.1 variant can be observed in DRB1*03, *11, and *1303 haplotypes. Based on the strong linkage disequilibria between DRB1-DQA1-DQB1 genes and between DRB1-QAP-DQA1, we have deduced the four-point haplotypes for DRB1-QAP-DQA1-DQB1 in patients and controls. Two haplotypes DRB1*02-QAP1.2-DQA1*0102-DQB1*0602 and DRB1*03-QAP4.1-DQA1*0501-DQB1*0201 are significantly increased in patients as compared to controls (p QAP, DQA1, and DQB1 as well as the investigation of the deduced DRB1-QAP-DQA1-DQB1 haplotypes leads to the conclusion that QAP4.1 and DQA1*0501 on the DR3 haplotypes are probably not involved in SLE susceptibility.(ABSTRACT TRUNCATED AT 400 WORDS)

  12. HDAC inhibitors TSA and sodium butyrate enhanced the human IL-5 expression by altering histone acetylation status at its promoter region.

    Science.gov (United States)

    Han, Songyan; Lu, Jun; Zhang, Yu; Cheng, Cao; Li, Lin; Han, Liping; Huang, Baiqu

    2007-02-15

    The expression of IL-5 correlated tightly with the maturation and differentiation of eosinophils, and is considered as a cytokine responsible for allergic inflammation. We report here that inhibition of HDAC activity by Trichostatin A (TSA) and sodium butyrate (NaBu), the two specific HDAC inhibitors, resulted in the elevation of both endogenous and exogenous activity of IL-5 promoter. We demonstrated that both the mRNA expression and protein production of IL-5 were stimulated by TSA and NaBu treatments. ChIP assays showed that treatments of TSA and NaBu caused hyperacetylation of histones H3 and H4 on IL-5 promoter in Jurkat cells, which consequently promoted the exogenous luciferase activity driven by this promoter. Moreover, site-directed mutagenesis studies showed that the binding sites for transcription factors NFAT, GATA3 and YY1 on IL-5 promoter were critical for the effects of TSA and NaBu, suggesting that the transcriptional activation of IL-5 gene by these inhibitors was achieved by affecting HDAC function on IL-5 promoter via transcription factors. These data will contribute to elucidating the unique mechanism of IL-5 transcriptional control and to the therapy of allergic disorders related to IL-5.

  13. A pilot study investigating of the nature of point-of-sale alcohol promotions in bottle shops in a large Australian regional city.

    Science.gov (United States)

    Jones, Sandra C; Lynch, Melissa

    2007-08-01

    The promotion of alcohol by retailers and media can contribute to a culture of excessive alcohol consumption, but the effect of non-advertising alcohol promotions has largely been neglected. This study sought to gather initial data on this important area. An observational study of alcohol point-of-sale promotions in the Wollongong CBD area, conducted in July-August 2005. We identified 17 different promotions in three categories: gift with purchase; competitions; and buy some, get some free. Given previous research demonstrating the relationship between increased alcohol consumption and both ownership of alcohol-related merchandise and reduced per unit price, it appears that point-of-sale promotions may have the potential to further increase alcohol consumption among young people. Only when the extent and impact of such promotions is demonstrated will we be in a position to effectively advocate for appropriate regulations to ensure young people are not exposed to marketing strategies that further increase their exposure to alcohol-related harms.

  14. Transverse Stress Fracture of the Proximal Patella: A Case Report.

    Science.gov (United States)

    Atsumi, Satoru; Arai, Yuji; Kato, Ko; Nishimura, Akinobu; Nakazora, Shigeto; Nakagawa, Shuji; Ikoma, Kazuya; Fujiwara, Hiroyoshi; Sudo, Akihiro; Kubo, Toshikazu

    2016-02-01

    Among stress fractures associated with sports activities, patellar stress fracture is rare. Regarding patella stress fractures, so far only distal transverse or lateral longitudinal fractures have been reported, but there are no reports of transverse fractures occurring in the proximal patella. We describe an extremely rare case of transverse stress fracture of proximal patella in a 9-year-old athlete.A 9-year old boy, who participated in sports (sprints and Kendo) presented with left knee pain without any external injury. In plain radiographs, a fracture line was observed in the proximal 1/3 of the left patella, and a patella stress fracture was diagnosed. For treatment, because 7 months of conservative therapy showed no improvement, internal fixation was carried out using Acutrak screws, and bone union was thus achieved. Three months after the operation, he was able to return to his previous level of athletic sports activity.Regarding the mechanism of onset, it is believed that the causes are longitudinal traction force and patellofemoral contact pressure. On the other hand, the contact region of the patella with the femur changes with the flexion angle of the knee. In the current case, the fracture occurred at a site where the patella was in contact with the femur at a flexion angle of >90°, so it is believed that it occurred as a clinical condition from being subjected to repeated longitudinal traction force and patellofemoral contact pressure at a flexion angle of >90°, during the sports activities of sprints and Kendo. The nonunion of the transverse stress fracture of his proximal patella was successfully treated with internal fixation using Acutrak screws.

  15. Repression of the aroF promoter by the TyrR repressor in Escherichia coli K-12: role of the 'upstream' operator site.

    Science.gov (United States)

    Cobbett, C S

    1988-05-01

    Three sequences are required for complete repression of the aroF promoter by the TyrR repressor protein. Two of these operator sites lie adjacent to each other and overlap the -35 region of the aroF promoter while the third lies about 70 base pairs upstream of the promoter. An aroF-cat (chloramphenicol acetyltransferase) gene fusion has been used to assay the effect of DNA insertions that alter the distance between the two promoter-proximal and the third, distal, operator sites on the repression of the aroF promoter in vivo. The distal site contributes to the repression of the promoter up to a distance of about 400 base pairs and its effect is not dependent on its separation from the first and second sites by an integral number of turns of the DNA helix.

  16. Factors affecting minority population proximity to hazardous facilities

    Energy Technology Data Exchange (ETDEWEB)

    Nieves, L.A. [Argonne National Lab., IL (United States); Nieves, A.L. [Wheaton Coll., IL (United States)]|[Argonne National Lab., IL (United States)

    1995-04-01

    Disproportionate exposure of minority groups to environmental hazards has been attributed to ``environmental racism`` by some authors, without systematic investigation of the factors underlying this exposure pattern. This study examines regional differences in the proximity of African-Americans, Hispanics, Asians, and non-Hispanic Whites to a broad range of facility types and explores the effects of urban and income factors. A statistically significant inverse relationship is found between the percentage of non-Hispanic Whites and virtually all facility categories in all regions. Except for Hispanics in the South, all such associations for minority groups show a direct relationship, though some are nonsignificant. The geographic concentration of facilities is more closely tied to urbanization than to economic factors. Controlling for both urban and economic factors, minority population concentration is still a significant explanatory variable for some facility types in some regions. This finding is most consistent for African-Americans.

  17. Locking plate fixation for proximal humerus fractures.

    LENUS (Irish Health Repository)

    Burke, Neil G

    2012-02-01

    Locking plates are increasingly used to surgically treat proximal humerus fractures. Knowledge of the bone quality of the proximal humerus is important. Studies have shown the medial and dorsal aspects of the proximal humeral head to have the highest bone strength, and this should be exploited by fixation techniques, particularly in elderly patients with osteoporosis. The goals of surgery for proximal humeral fractures should involve minimal soft tissue dissection and achieve anatomic reduction of the head complex with sufficient stability to allow for early shoulder mobilization. This article reviews various treatment options, in particular locking plate fixation. Locking plate fixation is associated with a high complication rate, such as avascular necrosis (7.9%), screw cutout (11.6%), and revision surgery (13.7%). These complications are frequently due to the varus deformation of the humeral head. Strategic screw placement in the humeral head would minimize the possibility of loss of fracture reduction and potential hardware complications. Locking plate fixation is a good surgical option for the management of proximal humerus fractures. Complications can be avoided by using better bone stock and by careful screw placement in the humeral head.

  18. Downstream Antisense Transcription Predicts Genomic Features That Define the Specific Chromatin Environment at Mammalian Promoters.

    Directory of Open Access Journals (Sweden)

    Christopher A Lavender

    2016-08-01

    Full Text Available Antisense transcription is a prevalent feature at mammalian promoters. Previous studies have primarily focused on antisense transcription initiating upstream of genes. Here, we characterize promoter-proximal antisense transcription downstream of gene transcription starts sites in human breast cancer cells, investigating the genomic context of downstream antisense transcription. We find extensive correlations between antisense transcription and features associated with the chromatin environment at gene promoters. Antisense transcription downstream of promoters is widespread, with antisense transcription initiation observed within 2 kb of 28% of gene transcription start sites. Antisense transcription initiates between nucleosomes regularly positioned downstream of these promoters. The nucleosomes between gene and downstream antisense transcription start sites carry histone modifications associated with active promoters, such as H3K4me3 and H3K27ac. This region is bound by chromatin remodeling and histone modifying complexes including SWI/SNF subunits and HDACs, suggesting that antisense transcription or resulting RNA transcripts contribute to the creation and maintenance of a promoter-associated chromatin environment. Downstream antisense transcription overlays additional regulatory features, such as transcription factor binding, DNA accessibility, and the downstream edge of promoter-associated CpG islands. These features suggest an important role for antisense transcription in the regulation of gene expression and the maintenance of a promoter-associated chromatin environment.

  19. Downstream Antisense Transcription Predicts Genomic Features That Define the Specific Chromatin Environment at Mammalian Promoters.

    Science.gov (United States)

    Lavender, Christopher A; Cannady, Kimberly R; Hoffman, Jackson A; Trotter, Kevin W; Gilchrist, Daniel A; Bennett, Brian D; Burkholder, Adam B; Burd, Craig J; Fargo, David C; Archer, Trevor K

    2016-08-01

    Antisense transcription is a prevalent feature at mammalian promoters. Previous studies have primarily focused on antisense transcription initiating upstream of genes. Here, we characterize promoter-proximal antisense transcription downstream of gene transcription starts sites in human breast cancer cells, investigating the genomic context of downstream antisense transcription. We find extensive correlations between antisense transcription and features associated with the chromatin environment at gene promoters. Antisense transcription downstream of promoters is widespread, with antisense transcription initiation observed within 2 kb of 28% of gene transcription start sites. Antisense transcription initiates between nucleosomes regularly positioned downstream of these promoters. The nucleosomes between gene and downstream antisense transcription start sites carry histone modifications associated with active promoters, such as H3K4me3 and H3K27ac. This region is bound by chromatin remodeling and histone modifying complexes including SWI/SNF subunits and HDACs, suggesting that antisense transcription or resulting RNA transcripts contribute to the creation and maintenance of a promoter-associated chromatin environment. Downstream antisense transcription overlays additional regulatory features, such as transcription factor binding, DNA accessibility, and the downstream edge of promoter-associated CpG islands. These features suggest an important role for antisense transcription in the regulation of gene expression and the maintenance of a promoter-associated chromatin environment.

  20. The effect of geographical proximity on scientific cooperation among Chinese cities from 1990 to 2010.

    Directory of Open Access Journals (Sweden)

    Haitao Ma

    Full Text Available The relations between geographical proximity and spatial distance constitute a popular topic of concern. Thus, how geographical proximity affects scientific cooperation, and whether geographically proximate scientific cooperation activities in fact exhibit geographic scale features should be investigated.Selected statistics from the ISI database on cooperatively authored papers, the authors of which resided in 60 typical cites in China, and which were published in the years 1990, 1995, 2000, 2005, and 2010, were used to establish matrices of geographic distance and cooperation levels between cities. By constructing a distance-cooperation model, the degree of scientific cooperation based on spatial distance was calculated. The relationship between geographical proximity and scientific cooperation, as well as changes in that relationship, was explored using the fitting function.(1 Instead of declining, the role of geographical proximity in inter-city scientific cooperation has increased gradually but significantly with the popularization of telecommunication technologies; (2 the relationship between geographical proximity and scientific cooperation has not followed a perfect declining curve, and at certain spatial scales, the distance-decay regularity does not work; (3 the Chinese scientific cooperation network gathers around different regional center cities, showing a trend towards a regional network; within this cooperation network the amount of inter-city cooperation occurring at close range increased greatly.The relationship between inter-city geographical distance and scientific cooperation has been enhanced and strengthened over time.

  1. The effect of geographical proximity on scientific cooperation among Chinese cities from 1990 to 2010.

    Science.gov (United States)

    Ma, Haitao; Fang, Chuanglin; Pang, Bo; Li, Guangdong

    2014-01-01

    The relations between geographical proximity and spatial distance constitute a popular topic of concern. Thus, how geographical proximity affects scientific cooperation, and whether geographically proximate scientific cooperation activities in fact exhibit geographic scale features should be investigated. Selected statistics from the ISI database on cooperatively authored papers, the authors of which resided in 60 typical cites in China, and which were published in the years 1990, 1995, 2000, 2005, and 2010, were used to establish matrices of geographic distance and cooperation levels between cities. By constructing a distance-cooperation model, the degree of scientific cooperation based on spatial distance was calculated. The relationship between geographical proximity and scientific cooperation, as well as changes in that relationship, was explored using the fitting function. (1) Instead of declining, the role of geographical proximity in inter-city scientific cooperation has increased gradually but significantly with the popularization of telecommunication technologies; (2) the relationship between geographical proximity and scientific cooperation has not followed a perfect declining curve, and at certain spatial scales, the distance-decay regularity does not work; (3) the Chinese scientific cooperation network gathers around different regional center cities, showing a trend towards a regional network; within this cooperation network the amount of inter-city cooperation occurring at close range increased greatly. The relationship between inter-city geographical distance and scientific cooperation has been enhanced and strengthened over time.

  2. Single nucleotide polymorphisms in the promoter region of the IL1B gene influence outcome in multiple myeloma patients treated with high-dose chemotherapy independently of relapse treatment with thalidomide and bortezomib

    DEFF Research Database (Denmark)

    Vangsted, Annette J.; Klausen, Tobias W.; Abildgaard, Niels

    2011-01-01

    the impact on outcome of HDT, INF-α maintenance treatment, and treatment with thalidomide and bortezomib at relapse, in relation to the major identified functional polymorphisms in the promoter region of IL1B. The wild-type C-allele of IL1B C-3737T and non-carriage of the IL1B promoter haplotype TGT (−3737T...... carriers at both loci. No relation to genotype and outcome was found for relapse patients treated with thalidomide or bortezomib. Our results indicate that a subpopulation of myeloma patients carrying the wild-type C-allele of IL1B C-3737T and non-carriers of the promoter haplotype TGT (−3737T, −1464G...

  3. Multiple domains for initiator binding proteins TFII-I and YY-1 are present in the initiator and upstream regions of the rat XDH/XO TATA-less promoter.

    Science.gov (United States)

    Clark, M P; Chow, C W; Rinaldo, J E; Chalkley, R

    1998-06-01

    We previously reported that the TATA-less rat xanthine dehydrogenase/oxidase (XDH/XO) promoter is organized with multiple initiator elements (Inr 1, 2, 3 and 4). Additionally, we identified six factor binding footprints in the upstream region of this promoter (FP 1-FP 6), two of which (FP 2 and FP 4) we showed to be C/EBP binding sites. In this report we continue our characterization of the XDH/XO promoter, detailing other cis elements which comprise the Inr and upstream binding factors. Interestingly, multiple binding domains for known initiator binding proteins, YY-1 and USF-related factor/TFII-I, have been identified which potentially play an important role in transcription initiation.

  4. Transcriptional Auto-Regulation of RUNX1 P1 Promoter.

    Directory of Open Access Journals (Sweden)

    Milka Martinez

    Full Text Available RUNX1 a member of the family of runt related transcription factors (RUNX, is essential for hematopoiesis. The expression of RUNX1 gene is controlled by two promoters; the distal P1 promoter and the proximal P2 promoter. Several isoforms of RUNX1 mRNA are generated through the use of both promoters and alternative splicing. These isoforms not only differs in their temporal expression pattern but also exhibit differences in tissue specificity. The RUNX1 isoforms derived from P2 are expressed in a variety of tissues, but expression of P1-derived isoform is restricted to cells of hematopoietic lineage. However, the control of hematopoietic-cell specific expression is poorly understood. Here we report regulation of P1-derived RUNX1 mRNA by RUNX1 protein. In silico analysis of P1 promoter revealed presence of two evolutionary conserved RUNX motifs, 0.6kb upstream of the transcription start site, and three RUNX motifs within 170bp of the 5'UTR. Transcriptional contribution of these RUNX motifs was studied in myeloid and T-cells. RUNX1 genomic fragment containing all sites show very low basal activity in both cell types. Mutation or deletion of RUNX motifs in the UTR enhances basal activity of the RUNX1 promoter. Chromatin immunoprecipitation revealed that RUNX1 protein is recruited to these sites. Overexpression of RUNX1 in non-hematopoietic cells results in a dose dependent activation of the RUNX1 P1 promoter. We also demonstrate that RUNX1 protein regulates transcription of endogenous RUNX1 mRNA in T-cell. Finally we show that SCL transcription factor is recruited to regions containing RUNX motifs in the promoter and the UTR and regulates activity of the RUNX1 P1 promoter in vitro. Thus, multiple lines of evidence show that RUNX1 protein regulates its own gene transcription.

  5. Industrial Computed Tomography using Proximal Algorithm

    KAUST Repository

    Zang, Guangming

    2016-04-14

    In this thesis, we present ProxiSART, a flexible proximal framework for robust 3D cone beam tomographic reconstruction based on the Simultaneous Algebraic Reconstruction Technique (SART). We derive the proximal operator for the SART algorithm and use it for minimizing the data term in a proximal algorithm. We show the flexibility of the framework by plugging in different powerful regularizers, and show its robustness in achieving better reconstruction results in the presence of noise and using fewer projections. We compare our framework to state-of-the-art methods and existing popular software tomography reconstruction packages, on both synthetic and real datasets, and show superior reconstruction quality, especially from noisy data and a small number of projections.

  6. Correlation between social proximity and mobility similarity.

    Science.gov (United States)

    Fan, Chao; Liu, Yiding; Huang, Junming; Rong, Zhihai; Zhou, Tao

    2017-09-20

    Human behaviors exhibit ubiquitous correlations in many aspects, such as individual and collective levels, temporal and spatial dimensions, content, social and geographical layers. With rich Internet data of online behaviors becoming available, it attracts academic interests to explore human mobility similarity from the perspective of social network proximity. Existent analysis shows a strong correlation between online social proximity and offline mobility similarity, namely, mobile records between friends are significantly more similar than between strangers, and those between friends with common neighbors are even more similar. We argue the importance of the number and diversity of common friends, with a counter intuitive finding that the number of common friends has no positive impact on mobility similarity while the diversity plays a key role, disagreeing with previous studies. Our analysis provides a novel view for better understanding the coupling between human online and offline behaviors, and will help model and predict human behaviors based on social proximity.

  7. [Disorders of sex development and proximal hypospadias].

    Science.gov (United States)

    Oswald, J

    2016-01-01

    Children with ambiguous genitalia due to different chromosome or gonadal sex are a particular challenge concerning the diagnostic and therapeutic implications. Proximal hypospadias patients with normal gonadal development should be distinguished from children with DSD (disorders of sex development) to guarantee normal gender identity and the best possible surgical therapy. This paper focuses on the terminology, embryology, and pathophysiology of the different manifestations of DSD. The state of knowledge about this disease pattern with particular emphasis on proximal hypospadias based on national and international scientific discussions is presented. The different clinical pictures as well as therapeutic options of DSD with a special focus on recent literature and giving particular attention to patients with proximal hypospadias are presented. Because of the complexity of patients suffering from disorders of sex development an interdisciplinary DSD healthcare team including a paediatric endocrinologist as well as paediatric urologist should be provided. These specialists enable an accurate diagnosis in severe hypospadias patients without reference to DSD diseases patterns.

  8. Infiltrating/sealing proximal caries lesions

    DEFF Research Database (Denmark)

    Martignon, S; Ekstrand, K R; Gomez, J

    2012-01-01

    This randomized split-mouth controlled clinical trial aimed at assessing the therapeutic effects of infiltration vs. sealing for controlling caries progression on proximal surfaces. Out of 90 adult students/patients assessed at university clinics and agreeing to participate, 39, each with 3...... differences in lesion progression between infiltration and placebo (P = 0.0012) and between sealing and placebo (P = 0.0269). The study showed that infiltration and sealing are significantly better than placebo treatment for controlling caries progression on proximal lesions. No significant difference...... proximal lesions identified radiographically around the enamel-dentin junction to the outer third of the dentin, were included. Lesions were randomly allocated for treatment to test-A (Infiltration: ICON-pre-product; DMG), test-B (Sealing: Prime-Bond-NT; Dentsply), or control-C (Placebo). Primary outcome...

  9. Impaired Regulation of ALDH2 Protein Expression Revealing a Yet Unknown Epigenetic Impact of rs886205 on Specific Methylation of a Negative Regulatory Promoter Region in Alcohol-Dependent Patients.

    Science.gov (United States)

    Haschemi Nassab, Mani; Rhein, Mathias; Hagemeier, Lars; Kaeser, Marius; Muschler, Marc; Glahn, Alexander; Pich, Andreas; Heberlein, Annemarie; Kornhuber, Johannes; Bleich, Stefan; Frieling, Helge; Hillemacher, Thomas

    2016-01-01

    Acetaldehyde, the carcinogenic metabolite of ethanol known to provoke aversive symptoms of alcohol consumption, is predominantly eliminated by aldehyde dehydrogenase 2 (ALDH2). Reduced ALDH2 activity correlates with low alcohol tolerance and low risk for alcohol dependence. The ALDH2 promoter polymorphism rs886205 (A>G) is associated with decreased promoter activity, but a molecular mechanism and allele-dependent ALDH2 protein expression has not been described yet. On the basis of allele-dependent epigenetic effects, we analyzed the rs886205 genotype, methylation rates of cytosine-phosphatidyl-guanine (CpG)-sites within a regulatory promoter region and ALDH2 protein levels in 82 alcohol-dependent patients during a 2-week withdrawal and compared them to 34 matched controls. Patients without the G-allele of rs886205 showed higher methylation of the promoter region than controls and readily adapted epigenetically as well as on protein level during withdrawal, while patients with the G-allele displayed retarded methylation readjustment and no change in ALDH2 protein levels. Our data provide novel insights into an unknown genetic-epigenetic interaction, revealing impaired ALDH2 protein expression in patients with the G-allele of rs886205. Additionally, we checked for an association between rs886205 and protection against alcohol dependence and found a trend association between the G-allele and protection against alcohol dependence that needs replication in a larger Caucasian cohort. © 2015 S. Karger AG, Basel.

  10. Knowledge networks in the Dutch aviation industry: The proximity paradox

    NARCIS (Netherlands)

    Broekel, T.; Boschma, R.A.

    2012-01-01

    The importance of geographical proximity for interaction and knowledge sharing has been discussed extensively in recent years. There is increasing consensus that geographical proximity is just one out of many types of proximities that might be relevant. We argue that proximity may be a crucial

  11. The developmental spectrum of proximal radioulnar synostosis

    Energy Technology Data Exchange (ETDEWEB)

    Elliott, Alison M. [University of Manitoba, Winnipeg Regional Health Association Program of Genetics and Metabolism, Winnipeg, MB (Canada); University of Manitoba, Department of Paediatrics and Child Health, Winnipeg, MB (Canada); University of Manitoba, Department of Biochemistry and Medical Genetics, Winnipeg, MB (Canada); University of Manitoba, WRHA Program of Genetics and Metabolism, Departments of Paediatrics and Child Health, Biochemistry and Medical Genetics, Winnipeg, MB (Canada); Kibria, Lisa [University of Manitoba, Department of School of Medical Rehabilitation, Winnipeg, MB (Canada); Reed, Martin H. [University of Manitoba, Department of Paediatrics and Child Health, Winnipeg, MB (Canada); University of Manitoba, Department of Biochemistry and Medical Genetics, Winnipeg, MB (Canada); University of Manitoba, Department of Diagnostic Imaging, Winnipeg, MB (Canada)

    2010-01-15

    Proximal radioulnar synostosis is a rare upper limb malformation. The elbow is first identifiable at 35 days (after conception), at which stage the cartilaginous anlagen of the humerus, radius and ulna are continuous. Subsequently, longitudinal segmentation produces separation of the distal radius and ulna. However, temporarily, the proximal ends are united and continue to share a common perichondrium. We investigated the hypothesis that posterior congenital dislocation of the radial head and proximal radioulnar fusion are different clinical manifestations of the same primary developmental abnormality. Records were searched for ''proximal radioulnar fusion/posterior radial head dislocation'' in patients followed at the local Children's Hospital and Rehabilitation Centre for Children. Relevant radiographic, demographic and clinical data were recorded. Ethics approval was obtained through the University Research Ethics Board. In total, 28 patients met the inclusion criteria. The majority of patients (16) had bilateral involvement; eight with posterior dislocation of the radial head only; five had posterior radial head dislocation with radioulnar fusion and two had radioulnar fusion without dislocation. One patient had bilateral proximal radioulnar fusion and posterior dislocation of the left radial head. Nine patients had only left-sided involvement, and three had only right-sided involvement.The degree of proximal fusion varied, with some patients showing 'complete' proximal fusion and others showing fusion that occurred slightly distal to the radial head: 'partially separated.' Associated disorders in our cohort included Poland syndrome (two patients), Cornelia de Lange syndrome, chromosome anomalies (including tetrasomy X) and Cenani Lenz syndactyly. The suggestion of a developmental relationship between posterior dislocation of the radial head and proximal radioulnar fusion is supported by the fact that both anomalies

  12. Uncemented allograft-prosthetic composite reconstruction of the proximal femur

    Directory of Open Access Journals (Sweden)

    Li Min

    2014-01-01

    Full Text Available Background: Allograft-prosthetic composite can be divided into three groups names cemented, uncemented, and partially cemented. Previous studies have mainly reported outcomes in cemented and partially cemented allograft-prosthetic composites, but have rarely focused on the uncemented allograft-prosthetic composites. The objectives of our study were to describe a surgical technique for using proximal femoral uncemented allograft-prosthetic composite and to present the radiographic and clinical results. Materials and Methods: Twelve patients who underwent uncemented allograft-prosthetic composite reconstruction of the proximal femur after bone tumor resection were retrospectively evaluated at an average followup of 24.0 months. Clinical records and radiographs were evaluated. Results: In our series, union occurred in all the patients (100%; range 5-9 months. Until the most recent followup, there were no cases with infection, nonunion of the greater trochanter, junctional bone resorption, dislocation, allergic reaction, wear of acetabulum socket, recurrence, and metastasis. But there were three periprosthetic fractures which were fixed using cerclage wire during surgery. Five cases had bone resorption in and around the greater trochanter. The average Musculoskeletal Tumor Society (MSTS score and Harris hip score (HHS were 26.2 points (range 24-29 points and 80.6 points (range 66.2-92.7 points, respectively. Conclusions: These results showed that uncemented allograft-prosthetic composite could promote bone union through compression at the host-allograft junction and is a good choice for proximal femoral resection. Although this technology has its own merits, long term outcomes are yet not validated.

  13. HPV16 oncogenes E6 or/and E7 may influence the methylation status of RASSFIA gene promoter region in cervical cancer cell line HT-3.

    Science.gov (United States)

    Yin, Fufen; Wang, Ning; Wang, Shanshan; Yu, Fengsheng; Sun, Xin; Yu, Xiao; Luo, Bing; Zhao, Chengquan; Wang, Yankui

    2017-04-01

    Both human papillomavirus (HPV) infection and the aberrant Ras associated domain family gene 1A (RASSF1A) promoter methylation status participate in the pathogenesis of cervical cancer. Some studies suggest that E6, and E7 are involved in the pathogenetic mechanisms of RASSF1A. We mainly explored a possible involvement of HPV16 oncogenes E6 or/and E7 in RASSF1A promoter methylation status and possible roles of RASSF1A gene methylation in cervical cancer. Bisulfite genomic sequencing (BGS) PCR combined with TA clone, methylation-specific PCR (MSP) were used to analyze methylation status of the RASSF1A gene promoter in HPV16/18-positive and HPV-negative cervical cancer cell lines; ectopically expressed HPV16 E6, E7 and E6/E7 cervical cancer cell lines; normal cervical and cervical cancer tissues. The mRNA and protein expression of RASSF1A was detected by RT-PCR and western blotting. Re-expression and downregulated promoter methylation status were detected in the ectopically expressed HPV16 E6 and E7 cervical cancer cell line HT-3. The methylation status and expression of RASSF1A could be downregulated or reactivated by 5-Aza-dc in HT-3 and C33A cells. Additionally, statistics showed significant hypermethylation of RASSF1A in cervical cancer samples compared to that in normal cervical samples (PHPV detection combining the MY09/11, GP5+/6+ and SPF1/2 methods. The ectopic expression of HPV16 E6 and/or E7 may be involved in aberrant methylation and expression of the RASSF1A gene. RASSF1A gene expression could be regulated by its promoter methylation status. Additionally, the false negativity of the HPV detection may contribute to the uncertain relationship between HPV infection and aberrant RASSF1A promoter methylation.

  14. The promoter of the cereal VERNALIZATION1 gene is sufficient for transcriptional induction by prolonged cold.

    Directory of Open Access Journals (Sweden)

    Maria M Alonso-Peral

    Full Text Available The VERNALIZATION1 (VRN1 gene of temperate cereals is transcriptionally activated by prolonged cold during winter (vernalization to promote flowering. To investigate the mechanisms controlling induction of VRN1 by prolonged cold, different regions of the VRN1 gene were fused to the GREEN FLUORESCENT PROTEIN (GFP reporter and expression of the resulting gene constructs was assayed in transgenic barley (Hordeum vulgare. A 2 kb segment of the promoter of VRN1 was sufficient for GFP expression in the leaves and shoot apex of transgenic barley plants. Fluorescence increased at the shoot apex prior to inflorescence initiation and was subsequently maintained in the developing inflorescence. The promoter was also sufficient for low-temperature induction of GFP expression. A naturally occurring insertion in the proximal promoter, which is associated with elevated VRN1 expression and early flowering in some spring wheats, did not abolish induction of VRN1 transcription by prolonged cold, however. A translational fusion of the promoter and transcribed regions of VRN1 to GFP, VRN1::GFP, was localised to nuclei of cells at the shoot apex of transgenic barley plants. The distribution of VRN1::GFP at the shoot apex was similar to the expression pattern of the VRN1 promoter-GFP reporter gene. Fluorescence from the VRN1::GFP fusion protein increased in the developing leaves after prolonged cold treatment. These observations suggest that the promoter of VRN1 is targeted by mechanisms that trigger vernalization-induced flowering in economically important temperate cereal crops.

  15. Function and regulation domains of a newly isolated putative β-actin promoter from pacific white shrimp.

    Directory of Open Access Journals (Sweden)

    Yingli Shi

    Full Text Available Current development of transgenic shrimp research has been hampered due to the lack of the suitable promoters and efficient transfection methods for crustaceans. A 1642 bp sequence, containing 5'-upstream sequence, exon 1, intron 1 and partial exon 2, which is responsible for transcriptional initiation of the newly reported shrimp β-actin (actinT1, has been isolated from the Pacific white shrimp (Litopenaeus vannamei and named as SbaP. To determine its function and potential application in marine biotechnology, the sequence and functional domains were examined by constitutive expression of the luciferase reporter gene. We have identified 5' regions that play a central role in the expression of the β-actin gene. The proximal promoter (-1642/-1325 contains two highly conserved transcriptional sites, CCAAT box and CArG motif. Two negative (-1140/-924, -222/-21 and one positive (-810/-425 regulatory elements have been identified in intron1. Transient transfection assay with a construct containing proximal promoter and enhancer (SbaPΔ-222/+1Δ-1325/-924 regions of the shrimp β-actin coupled with luciferase and EGFP (enhanced green fluorescent protein showed that the promoter was not only functional in sf21 cells, but promoter activity was more than 8-fold higher than a viral-origin promoter (ie1, white spot syndrome virus immediate early gene promoter. Furthermore, SbaPΔ-222/+1Δ-1325/-924 drove a successful expression of luciferase injection assay in vivo injection and also showed higher promoter activity than the ie1 promoter, suggesting that the expression vectors constructed with SbaPΔ-222/+1Δ-1325/-924 have important potential in gene transfer studies for shrimp and other crustacean species.

  16. PTSD and DNA Methylation in Select Immune Function Gene Promoter Regions: A Repeated Measures Case-control Study of U.S. Military Service Members

    Science.gov (United States)

    2013-06-24

    Johanning, 2002) smoking (Toh et al., 2010), and alcohol consumption (Seitz and Stickel, 2007; Toh et al., 2010; Zhu et al., 2012). Ascertainment of...IL8 gene promoter in oral cells of smok- ers and non-smokers with chronic periodontitis . J. Clin. Periodon- tol. 36, 719–725. doi:10.1111/j.1600- 051X

  17. An expression system based on the promoter region of the Aspergillus awamori 1,4-bèta-endoxylanase A gene

    NARCIS (Netherlands)

    Gouka, R.J.; Hessing, J.G.M.; Punt, P.J.; Stam, H.; Musters, W.; Hondel, C.A.M.J.J. van den

    1996-01-01

    A new, highly inducible fungal promoter derived from the Aspergillus awamori 1,4-β-endoxylanase A (exlA) gene is described. Induction analysis, carried out with the wild-type strain in shake flasks, showed that exlA expression is regulated at the transcriptional level. Using a β-glucuronidase (uidA)

  18. Serum osteoprotegerin (OPG) and the A163G polymorphism in the OPG promoter region are related to peripheral measures of bone mass and fracture odds ratios

    DEFF Research Database (Denmark)

    Jørgensen, Henrik L; Kusk, Philip; Madsen, Bente Elmfelt

    2004-01-01

    The purpose of this study is to investigate the association of serum osteoprotegerin (OPG) and the A163G polymorphism in the OPG promoter with peripheral measures of bone mass and with odds ratios for wrist and hip fracture in a case-control study of postmenopausal Danish women. The study included...

  19. The Effect of Point of Sale Promotions on the Alcohol Purchasing Behaviour of Young People in Metropolitan, Regional and Rural Australia

    Science.gov (United States)

    Jones, Sandra C.; Smith, Kylie M.

    2011-01-01

    This study, part of a larger project examining marketing and alcohol, looked specifically at the effects of point of sale (POS) promotions on young people, with a view to providing evidence which could be used to inform policy and regulation in this area. A series of focus groups were conducted in three different locations with young people aged…

  20. Method to measure tone of axial and proximal muscle.

    Science.gov (United States)

    Gurfinkel, Victor S; Cacciatore, Timothy W; Cordo, Paul J; Horak, Fay B

    2011-12-14

    The control of tonic muscular activity remains poorly understood. While abnormal tone is commonly assessed clinically by measuring the passive resistance of relaxed limbs, no systems are available to study tonic muscle control in a natural, active state of antigravity support. We have developed a device (Twister) to study tonic regulation of axial and proximal muscles during active postural maintenance (i.e. postural tone). Twister rotates axial body regions relative to each other about the vertical axis during stance, so as to twist the neck, trunk or hip regions. This twisting imposes length changes on axial muscles without changing the body's relationship to gravity. Because Twister does not provide postural support, tone must be regulated to counteract gravitational torques. We quantify this tonic regulation by the restive torque to twisting, which reflects the state of all muscles undergoing length changes, as well as by electromyography of relevant muscles. Because tone is characterized by long-lasting low-level muscle activity, tonic control is studied with slow movements that produce "tonic" changes in muscle length, without evoking fast "phasic" responses. Twister can be reconfigured to study various aspects of muscle tone, such as co-contraction, tonic modulation to postural changes, tonic interactions across body segments, as well as perceptual thresholds to slow axial rotation. Twister can also be used to provide a quantitative measurement of the effects of disease on axial and proximal postural tone and assess the efficacy of intervention.

  1. Method to Measure Tone of Axial and Proximal Muscle

    Science.gov (United States)

    Gurfinkel, Victor S.; Cacciatore, Timothy W.; Cordo, Paul J.; Horak, Fay B.

    2011-01-01

    The control of tonic muscular activity remains poorly understood. While abnormal tone is commonly assessed clinically by measuring the passive resistance of relaxed limbs1, no systems are available to study tonic muscle control in a natural, active state of antigravity support. We have developed a device (Twister) to study tonic regulation of axial and proximal muscles during active postural maintenance (i.e. postural tone). Twister rotates axial body regions relative to each other about the vertical axis during stance, so as to twist the neck, trunk or hip regions. This twisting imposes length changes on axial muscles without changing the body's relationship to gravity. Because Twister does not provide postural support, tone must be regulated to counteract gravitational torques. We quantify this tonic regulation by the restive torque to twisting, which reflects the state of all muscles undergoing length changes, as well as by electromyography of relevant muscles. Because tone is characterized by long-lasting low-level muscle activity, tonic control is studied with slow movements that produce "tonic" changes in muscle length, without evoking fast "phasic" responses. Twister can be reconfigured to study various aspects of muscle tone, such as co-contraction, tonic modulation to postural changes, tonic interactions across body segments, as well as perceptual thresholds to slow axial rotation. Twister can also be used to provide a quantitative measurement of the effects of disease on axial and proximal postural tone and assess the efficacy of intervention. PMID:22214974

  2. Thumb proximal phalanx reconstruction with nonvascularized corticocancellous olecranon bone graft.

    Science.gov (United States)

    Soong, Maximillian

    2015-01-01

    Large segmental bone defects of the phalanges reportedly have been treated with free vascularized grafts from the hand, foot, or knee, or with nonvascularized grafts from the iliac crest. A nonvascularized structural corticocancellous graft from a local site would be advantageous. The olecranon has been used as a source of both cancellous and corticocancellous graft. The authors describe a unique case of the use of nonvascularized corticocancellous olecranon bone graft for structural purposes in a mutilating thumb injury. The patient injured the left thumb with a miter saw, resulting in a large degloving wound over a severely comminuted fracture of the proximal phalanx, with segmental bone loss between a base fragment and displaced condylar fragments. Provisional pin fixation was performed at the time of initial emergent irrigation and debridement, along with repairs of the extensor pollicis longus, radial digital nerve, and dorsal digital nerve. This was followed 3 weeks later by non-vascularized corticocancellous bone grafting from the olecranon to the proximal phalanx under regional anesthesia. The thumb was mobilized at 11 weeks, and solid union was radiographically confirmed at 6 months. The patient achieved moderate active range of motion and was able to return to work as a physical therapist. The elbow healed uneventfully and without pain or fracture at the donor site. This case shows that robust structural bone graft for the phalanges may be obtained from the nearby olecranon, under regional anesthesia, without microsurgery, and with potential advantages over the iliac crest. Copyright 2015, SLACK Incorporated.

  3. preliminary phytochemical screening, proximate and elemental

    African Journals Online (AJOL)

    DR. AMINU

    ABSTRACT. The seed powder of Moringa oleifera was analysed for its phytochemical, proximate and elemental composition using Folin-Denis spectrophotometric method, gravimetric method and energy dispersing X-ray fluorescence (EDXRF) transmission emission technique respectively. The seed powder had the ...

  4. Proximate, mineral composition, antioxidant activity, and total ...

    African Journals Online (AJOL)

    Four varieties of the red pepper fruits (Capsicum species) were evaluated for chemical composition, antioxidant activity and total phenolic contents using standard analytical technique, ferric-ion reducing antioxidant potential (FRAP) assay and Folin-Colcalteau method respectively. The proximate composition values ...

  5. 9__43 - 50__Tijjani_Proximate

    African Journals Online (AJOL)

    User

    Sena et al., 1998). In Nigeria, the plant is commonly consumed by the Hausa speaking communities as a spice and a sauce (Ibrahim et al., 2012). However, during preparation the leaves and stem are not carefully separated before processing of food. Thus, the present study was aimed at evaluating the proximate, minerals ...

  6. Phytochemistry and proximate composition of ginger ( Zingiber ...

    African Journals Online (AJOL)

    ... a little crude fibre content of 0.92 %. The results indicated that ginger rhizome is an excellent natural remedy for a wide range of ailments. Keywords: Zingiber officinale, spice, rhizome, phytochemistry, proximate analysis, Zingiberaceae, zingerone, methanolic extraction. Journal of Pharmaceutical and Allied Sciences, Vol.

  7. DEPRESSIONARY EFFECT OF PROXIMITY OF RESIDENTIAL ...

    African Journals Online (AJOL)

    Osondu

    2012-10-24

    Oct 24, 2012 ... opinions are analyzed and it revealed that the site has major impacts on the residents perceived quality of life, security and ... Key words: Landfill, Property value, Health and safety, Residential property, Solous. Introduction. The location ... Proximity to landfills and hazardous waste sites can severely affect ...

  8. 182 179 Comparative Study on the Proximate

    African Journals Online (AJOL)

    2008-12-02

    Dec 2, 2008 ... Key words: Annona squamosa, Fruits, Proximate, Minerals, nutrient density. INTRODUCTION. Sugar apple (Annona squamosa) also called. “Gwanda masar” in Hausa belong to the family. Annonacae. The most widely grown of all the species are A. muricata, A. cherimola, A reticulata, A. senegalensis and ...

  9. Phytochemical Screening, Proximate and Mineral Composition of ...

    African Journals Online (AJOL)

    Leaves of sweet potato (Ipomoea batatas) grown in Tepi area was studied for their class of phytochemicals, mineral and proximate composition using standard analytical methods. The phytochemical screening revealed the presence of alkaloids, flavonoid, terpenoids, saponins, quinones, phenol, tannins, amino acid and ...

  10. Phytochemical screening, proximate and elemental analysis of ...

    African Journals Online (AJOL)

    Citrus sinensis was screened for its phytochemical composition and was evaluated for the proximate and elemental analysis. The phytochemical analysis indicated the presence of reducing sugar, saponins, cardiac glycosides, tannins and flavonoids. The elemental analysis indicated the presence of the following mineral ...

  11. Phytochemical Screening and Proximate Analysis of Newbouldia ...

    African Journals Online (AJOL)

    The study was conducted to assess the phytochemical and proximate composition of Newboudia laevis leaves and Allium sativum bulb extracts. The leaves and bulbs extracts were analyzed for their chemical composition and antinutritional factors (ANFs) which include moisture, crude protein, crude fat, crude fiber, total ash ...

  12. Disability occurrence and proximity to death

    NARCIS (Netherlands)

    Klijs, Bart; Mackenbach, Johan P.; Kunst, Anton E.

    2010-01-01

    Purpose. This paper aims to assess whether disability occurrence is related more strongly to proximity to death than to age. Method. Self reported disability and vital status were available from six annual waves and a subsequent 12-year mortality follow-up of the Dutch GLOBE longitudinal study.

  13. [Four family members with proximal myotonic myopathy

    NARCIS (Netherlands)

    Tieleman, A.A.; Velden, M.P. van der; Visser, M.C.; Wokke, J.H.J.; Scheffer, H.; Engelen, B.G.M. van

    2004-01-01

    A 41-year-old woman had a 15-year history of pain in her thighs and arms, which also became weaker, and a decrease in visual acuity. Her 35-year-old brother, their 38-year-old sister and their 64-year-old mother also had myalgia, myotonia and proximal muscle weakness, and the women also had

  14. Phytochemical screening, proximate and elemental analysis of ...

    African Journals Online (AJOL)

    ... was about 0.01 in concentration. Proximate analysis also shows that it has a high nutritional value such as carbohydrate, fibre, Ash, fat and protein. These results recommended the consumption of these peels of desired physiochemical properties as sources of food fibres or low-calorie bulk ingredients in food applications ...

  15. Proximate composition and consumer acceptability of African ...

    African Journals Online (AJOL)

    The aim of the study was to assess the organoleptic differences of Clarias gariepinus smoked with two different energy sources, Anogeissus leiocarpus and Tamarindus indica with the help of a hedonic scale and to determine possible proximate composition difference between the smoked products. Smoking of the fishes ...

  16. Controllable proximity effect in superconducting hybrid devices

    NARCIS (Netherlands)

    Bakurskiy, S.V.

    2015-01-01

    This thesis is devoted to the study of controllable proximity effects in superconductors, both in terms of fundamental aspects and applications. As a part of this thesis theoretical description was suggested for a number of structures with superconducting electrodes and multiple interlayers. These

  17. Proximate, chemical compositions and sulphur concentrations on ...

    African Journals Online (AJOL)

    0, 10, 20, 50, 100, 150, 200, 250 and 300 ppm) on the nutritional value and the proximate composition of six selected mango cultivars (Tommy Atkins, Peach, Saber, Sunshine, Keitt and Vhavenda) grown in South Africa. The study shows that ...

  18. Proximate composition, bread characteristics and sensory ...

    African Journals Online (AJOL)

    This study was carried out to investigate proximate composition, bread characteristics and sensory evaluation of cocoyam-wheat composite breads at different levels of cocoyam flour substitution for human consumption.A whole wheat bread (WWB) and cocoyam-composite breads (CCB1,CCB 2 and CCB 3) were prepared ...

  19. Evaluation of the Proximate, Chemical and Phytochemical ...

    African Journals Online (AJOL)

    The increased interest in the utilization of the leaves of Moringa oleifera necessitated this study which evaluated the proximate, chemical and phytochemical composition, especially the presence of anti- physiological and toxic factors in the leaves. The results of the phytochemical analyses were: alkaloid 1.24 ± 0.141%; ...

  20. comparative proximate composition and antioxidant vitamins

    African Journals Online (AJOL)

    DR. AMINU

    ABSTRACT. The proximate composition and antioxidant vitamins analysis of two varieties of honey (dark amber and light amber) were carried out using standard methods. The values for moisture, ash, crude lipid, crude protein and crude carbohydrate contents of the two honeys, (light amber and dark amber) are 9.39 ...

  1. Proximate composition and cholesterol concentrations of ...

    African Journals Online (AJOL)

    Proximate composition and cholesterol concentrations of Rhynchophorus phoenicis and Oryctes monoceros larvae subjected to different heat treatments. ... 514.63 mg/100g dry weight basis (DWB) for raw and fried samples, respectively, but decreased to 295.20 mg/100 g DWB in the smoke-dried samples. Similarly, the ...

  2. Preliminary Phytochemical Screening, Elemental and Proximate ...

    African Journals Online (AJOL)

    The study aimed at phytochemical screening, elemental and proximate composition of two varieties of Cyperus esculentus (tiger nut) big yellow and small brown nuts using standard methods. The phytochemicals tested for were alkaloid, saponin, tannin, glycoside, flavonoid, steroid and resin. All the aforementioned ...

  3. Protein biomarker validation via proximity ligation assays.

    Science.gov (United States)

    Blokzijl, A; Nong, R; Darmanis, S; Hertz, E; Landegren, U; Kamali-Moghaddam, M

    2014-05-01

    The ability to detect minute amounts of specific proteins or protein modifications in blood as biomarkers for a plethora of human pathological conditions holds great promise for future medicine. Despite a large number of plausible candidate protein biomarkers published annually, the translation to clinical use is impeded by factors such as the required size of the initial studies, and limitations of the technologies used. The proximity ligation assay (PLA) is a versatile molecular tool that has the potential to address some obstacles, both in validation of biomarkers previously discovered using other techniques, and for future routine clinical diagnostic needs. The enhanced specificity of PLA extends the opportunities for large-scale, high-performance analyses of proteins. Besides advantages in the form of minimal sample consumption and an extended dynamic range, the PLA technique allows flexible assay reconfiguration. The technology can be adapted for detecting protein complexes, proximity between proteins in extracellular vesicles or in circulating tumor cells, and to address multiple post-translational modifications in the same protein molecule. We discuss herein requirements for biomarker validation, and how PLA may play an increasing role in this regard. We describe some recent developments of the technology, including proximity extension assays, the use of recombinant affinity reagents suitable for use in proximity assays, and the potential for single cell proteomics. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge. © 2013.

  4. Phytochemical screening, proximate and elemental analysis of ...

    African Journals Online (AJOL)

    Michael Horsfall

    2009). The aim of this study was to analyses the extract of. Citrus sinensis peels for the phytochemical, proximate and elemental composition. MATERIALS AND METHODS. Plant materials Fresh peels of Citrus sinensis were collected from Uselu market in Benin City, Edo. State, Nigeria. It was identified and authenticated by.

  5. Keldysh proximity action for disordered superconductors

    Indian Academy of Sciences (India)

    Abstract. We review a novel approach to the superconductive proximity effect in dis- ordered normal–superconducting (N–S) structures. The method is based on the multi- charge Keldysh action and is suitable for the treatment of interaction and fluctuation effects. As an application of the formalism, we study the subgap ...

  6. Goal-Proximity Decision-Making

    Science.gov (United States)

    Veksler, Vladislav D.; Gray, Wayne D.; Schoelles, Michael J.

    2013-01-01

    Reinforcement learning (RL) models of decision-making cannot account for human decisions in the absence of prior reward or punishment. We propose a mechanism for choosing among available options based on goal-option association strengths, where association strengths between objects represent previously experienced object proximity. The proposed…

  7. Promoter interference mediated by the U3 region in early-generation HIV-1-derived lentivirus vectors can influence detection of transgene expression in a cell-type and species-specific manner.

    Science.gov (United States)

    Ginn, Samantha L; Fleming, Jane; Rowe, Peter B; Alexander, Ian E

    2003-08-10

    In a previous study using an early-generation VSV-G-pseudotyped lentivirus vector encoding enhanced green fluorescent protein (EGFP) under the transcriptional control of a human cytomegalovirus (CMV) immediate-early promoter, we examined transduction efficiency in dissociated dorsal root ganglia (DRG) cultures. In cultures of murine origin, transgene expression was observed solely in the sensory neurons with the stromal cell population failing to show evidence of transduction. In contrast, efficient and sustained transduction of both sensory neurons and the stromal cell population was observed in cultures of human origin. Given the widespread use of murine models in preclinical gene therapy studies, in the current study we investigated the basis of this apparent neuron specificity of lentivirus-mediated transduction in murine DRG cultures. The interspecies differences persisted at high multiplicities of infection, and irrespective of whether lentiviral vector stocks were packaged in the presence or absence of human immunodeficiency virus type 1 (HIV-1) accessory proteins. Cell-type specificity of CMV promoter expression, tropism of the VSV-G envelope, and blocks to molecular transduction were also precluded as possible mechanisms, thereby implicating transcriptional repression of the internal heterologous promoter. This promoter interference effect was found to be mediated by cis-acting sequences upstream of the core promoter elements located in the U3 region of the proviral long terminal repeats (LTRs). Deletion of this region, as in late-generation self-inactivating (SIN) lentivirus vectors, relieves this effect. This provides a basis for reevaluating data produced using early-generation U3-bearing lentivirus vectors and for reconciling these with results obtained using more contemporary SIN lentivirus vectors carrying a U3 deletion.

  8. Small scale integrated agriculture: a tool of poverty alleviation, gender equality promotion and improving food security at household level in coastal region of Bangladesh

    Directory of Open Access Journals (Sweden)

    MR Begum

    2015-12-01

    Full Text Available The chemical composition of four edible plant foods species, three fish species and one prawn were analyzed in Food Chemistry Laboratory of Behbahan Khatam Alanbia University of Technology, Behbahan, Iran in 2014. The analysis of fatty acid and sugars composition were performed by gas liquid chromatography and high performance liquid chromatography, respectively. Protein and lipid content were founded higher in baked and fried in fish S. commersonnianus (74.29%, (20.20%, fish Sphyraena helleri (88.12% and (17.77%, respectively. Ash content in fish S. commersonnianus varies from 9.80% to 15.34%, and in fish S. helleri from 5.83% to 7.68%. Based on the proximate analysis, it can be calculated that an edible portion of 100 g of studied edible plant foods provides, on average, around 303.9±1.04 kcal. The plant Portulaca neglecta is suitable for high temperature food processes. The macronutrient profile in general revealed that the wild plant foods were with rich sources of protein and carbohydrates, and had low amounts of fat. The highest protein, the lowest fat and energy contents were found in boiled in both fish species; therefore, boiling can be recommended as the best cooking method for healthy diet.

  9. Effects of proximal and distal robot-assisted upper limb rehabilitation on chronic stroke recovery.

    Science.gov (United States)

    Mazzoleni, Stefano; Sale, Patrizio; Franceschini, Marco; Bigazzi, Samuele; Carrozza, Maria Chiara; Dario, Paolo; Posteraro, Federico

    2013-01-01

    To evaluate the effects of add-on distal upper limb robot-assisted treatment on the outcome of proximal regions. 64 chronic stroke patients divided into two groups participated in the study. Group A was assigned to the proximal robot-assisted rehabilitation, Group B to the proximal and distal. Shoulder/elbow subsection of Fugl-Meyer Assessment scale was collected for Group A, whereas for Group B wrist subsection was also collected. Motricity Index was used and a set of kinematic parameters was computed for both groups. A decrease in impairment after the treatment in both groups of patients (Group A: Shoulder/elbow FM p robot-assisted treatment in both groups; group B showed a greater improvement in velocity. Robotic treatment is effective to reduce motor impairment in chronic stroke patients even if distal training added to proximal segments in the Group B does not provide any incremental benefit to the proximal segments. It remains unclear if the effectiveness of robot-assisted treatment is directly related to the upper limb segment specifically treated and which order may lead to better outcome. Our study suggests that kinematic parameters should be computed in order to better clarify the role of distal training (wrist) on proximal segments (shoulder/elbow) as well.

  10. Altered DNA methylation patterns of the H19 differentially methylated region and the DAZL gene promoter are associated with defective human sperm.

    Directory of Open Access Journals (Sweden)

    Bo Li

    Full Text Available DNA methylation disturbance is associated with defective human sperm. However, oligozoospermia (OZ and asthenozoospermia (AZ usually present together, and the relationship between the single-phenotype defects in human sperm and DNA methylation is poorly understood. In this study, 20 infertile OZ patients and 20 infertile AZ patients were compared with 20 fertile normozoospermic men. Bisulfate-specific PCR was used to analyze DNA methylation of the H19-DMR and the DAZL promoter in these subjects. A similar DNA methylation pattern of the H19-DMR was detected in AZ and NZ(control, with only complete methylation and mild hypomethylation(0.05. However, the methylation pattern of severe hypomethylation (>50% unmethylated CpGs and complete unmethylation was only detected in 5 OZ patients, and the occurrence of these two methylation patterns was 8.54±10.86% and 9±6.06%, respectively. Loss of DNA methylation of the H19-DMR in the OZ patients was found to mainly occur in CTCF-binding site 6, with occurrence of 18.15±14.71%, which was much higher than that in patients with NZ (0.84±2.05% and AZ (0.58±1.77% (P20% methylated clones in the DAZL promoter only in infertile patients, there was no significant difference between the AZ and OZ patients in the proportion of moderately-to-severely hypermethylated clones (p>0.05. In all cases, global sperm genome methylation analyses, using LINE1 transposon as the indicator, showed that dysregulation of DNA methylation is specifically associated with the H19-DMR and DAZL promoter. Therefore, abnormal DNA methylation status of H19-DMR, especially at the CTCF-binding site 6, is closely associated with OZ. Abnormal DNA methylation of the DAZL promoter might represent an epigenetic marker of male infertility.

  11. An HDAC2-TET1 switch at distinct chromatin regions significantly promotes the maturation of pre-iPS to iPS cells.

    Science.gov (United States)

    Wei, Tingyi; Chen, Wen; Wang, Xiukun; Zhang, Man; Chen, Jiayu; Zhu, Songcheng; Chen, Long; Yang, Dandan; Wang, Guiying; Jia, Wenwen; Yu, Yangyang; Duan, Tao; Wu, Minjuan; Liu, Houqi; Gao, Shaorong; Kang, Jiuhong

    2015-06-23

    The maturation of induced pluripotent stem cells (iPS) is one of the limiting steps of somatic cell reprogramming, but the underlying mechanism is largely unknown. Here, we reported that knockdown of histone deacetylase 2 (HDAC2) specifically promoted the maturation of iPS cells. Further studies showed that HDAC2 knockdown significantly increased histone acetylation, facilitated TET1 binding and DNA demethylation at the promoters of iPS cell maturation-related genes during the transition of pre-iPS cells to a fully reprogrammed state. We also found that HDAC2 competed with TET1 in the binding of the RbAp46 protein at the promoters of maturation genes and knockdown of TET1 markedly prevented the activation of these genes. Collectively, our data not only demonstrated a novel intrinsic mechanism that the HDAC2-TET1 switch critically regulates iPS cell maturation, but also revealed an underlying mechanism of the interplay between histone acetylation and DNA demethylation in gene regulation. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  12. Molecular cloning of a cDNA encoding human SPH-binding factor, a conserved protein that binds to the enhancer-like region of the U6 small nuclear RNA gene promoter.

    Science.gov (United States)

    Rincon, J C; Engler, S K; Hargrove, B W; Kunkel, G R

    1998-11-01

    Many vertebrate small nuclear RNA gene promoters contain an SPH motif in their distal control regions that can confer transcriptional stimulation by RNA polymerase II or RNA polymerase III. Using the human U6 gene SPH motif as a probe, we isolated a cDNA encoding human SPH-binding factor (hSBF) from a HeLa cell expression library. The coding region of hSBF is almost identical to ZNF143, a 626 amino acid, seven zinc finger protein of previously unknown function. Furthermore, the predicted amino acid sequence of hSBF is highly homologous to Xenopus laevis and mouse Staf proteins, that bind to SPH motifs and stimulate transcription of selenocysteine tRNA gene promoters. Recombinant hSBF expressed in vitro or from Escherichia coli bound specifically to the human U6 gene SPH motif as shown by DNase I footprinting and electrophoretic mobility shift assays using various mutant SPH sites as competitors. Antibodies prepared against recombinant hSBF inhibited assembly of native SBF-DNA complexes. Immunodepleted HeLa S100 transcription extract no longer supported elevated levels of transcription by RNA polymerase III from a U6 promoter containing an SPH motif, whereas addition of recombinant hSBF protein to the immunodepleted extract reconstituted stimulated transcription.

  13. Internal fixation of proximal humerus fractures using the T2-proximal humeral nail.

    Science.gov (United States)

    Popescu, Dragos; Fernandez-Valencia, Jenaro A; Rios, Moisés; Cuñé, Jordi; Domingo, Anna; Prat, Salvi

    2009-09-01

    Surgical management of proximal humerus fractures remains controversial and there is an increasing interest in intramedullary nailing. Created to improve previous designs, the T2-proximal humeral nail (PHN) (Stryker) has been recently released, and the English literature lacks a series evaluating its results. We present a clinical prospective study evaluating this implant for proximal humeral fractures. We evaluated the functional and radiological results and possible complications. Twenty-nine patients with displaced fractures of the proximal humerus were treated with this nail. One patient was lost right after surgery and excluded from the assessment. Eighteen patients were older than 70 years. There were 21 fractures of the proximal part of the humerus and 7 fractures that also involved the shaft; 15 of the fractures were two-part fractures (surgical neck), 5 were three-part fractures, and 1 was a four-part fracture. All fractures healed in a mean period of 2.7 months. There was one delayed union that healed in 4 months. One case of avascular necrosis of the humeral head was observed (a four-part fracture), but remained asymptomatic and did not require further treatment. In one case a back-out of one proximal screw was observed. A final evaluation with a minimum 1 year follow-up was performed by an independent observer; in 18 patients, the mean Constant score was 65.7 or 76.1% with the adjustment of age and gender; in 19 patients, the mean Oxford Shoulder Score was 21.7. The results obtained with the T2-PHN nail indicate that it represents a safe and reliable method in the treatment of two- and three-part fractures of the proximal humerus. The proximal fixation mechanism diminishes the rate of back-out of the screws, a frequent complication described in the literature. Better functional results were obtained from the patients younger than 70 years, but these were not statistically significant.

  14. Proximal tubular hypertrophy and enlarged glomerular and proximal tubular urinary space in obese subjects with proteinuria.

    Directory of Open Access Journals (Sweden)

    Ana Tobar

    Full Text Available BACKGROUND: Obesity is associated with glomerular hyperfiltration, increased proximal tubular sodium reabsorption, glomerular enlargement and renal hypertrophy. A single experimental study reported an increased glomerular urinary space in obese dogs. Whether proximal tubular volume is increased in obese subjects and whether their glomerular and tubular urinary spaces are enlarged is unknown. OBJECTIVE: To determine whether proximal tubules and glomerular and tubular urinary space are enlarged in obese subjects with proteinuria and glomerular hyperfiltration. METHODS: Kidney biopsies from 11 non-diabetic obese with proteinuria and 14 non-diabetic lean patients with a creatinine clearance above 50 ml/min and with mild or no interstitial fibrosis were retrospectively analyzed using morphometric methods. The cross-sectional area of the proximal tubular epithelium and lumen, the volume of the glomerular tuft and of Bowman's space and the nuclei number per tubular profile were estimated. RESULTS: Creatinine clearance was higher in the obese than in the lean group (P=0.03. Proteinuria was similarly increased in both groups. Compared to the lean group, the obese group displayed a 104% higher glomerular tuft volume (P=0.001, a 94% higher Bowman's space volume (P=0.003, a 33% higher cross-sectional area of the proximal tubular epithelium (P=0.02 and a 54% higher cross-sectional area of the proximal tubular lumen (P=0.01. The nuclei number per proximal tubular profile was similar in both groups, suggesting that the increase in tubular volume is due to hypertrophy and not to hyperplasia. CONCLUSIONS: Obesity-related glomerular hyperfiltration is associated with proximal tubular epithelial hypertrophy and increased glomerular and tubular urinary space volume in subjects with proteinuria. The expanded glomerular and urinary space is probably a direct consequence of glomerular hyperfiltration. These effects may be involved in the pathogenesis of obesity

  15. Renal proximal tubule angiotensin AT1A receptors regulate blood pressure.

    Science.gov (United States)

    Li, Huiping; Weatherford, Eric T; Davis, Deborah R; Keen, Henry L; Grobe, Justin L; Daugherty, Alan; Cassis, Lisa A; Allen, Andrew M; Sigmund, Curt D

    2011-10-01

    All components of the renin angiotensin system necessary for ANG II generation and action have been reported to be present in renal proximal convoluted tubules. Given the close relationship between renal sodium handling and blood pressure regulation, we hypothesized that modulating the action of ANG II specifically in the renal proximal tubules would alter the chronic level of blood pressure. To test this, we used a proximal tubule-specific, androgen-dependent, promoter construct (KAP2) to generate mice with either overexpression of a constitutively active angiotensin type 1A receptor transgene or depletion of endogenous angiotensin type 1A receptors. Androgen administration to female transgenic mice caused a robust induction of the transgene in the kidney and increased baseline blood pressure. In the receptor-depleted mice, androgen administration to females resulted in a Cre recombinase-mediated deletion of angiotensin type 1A receptors in the proximal tubule and reduced blood pressure. In contrast to the changes observed at baseline, there was no difference in the blood pressure response to a pressor dose of ANG II in either experimental model. These data, from two separate mouse models, provide evidence that ANG II signaling via the type 1A receptor in the renal proximal tubule is a regulator of systemic blood pressure under baseline conditions.

  16. Alternative promoters and repetitive DNA elements define the species-dependent tissue-specific expression of the FMO1 genes of human and mouse.

    Science.gov (United States)

    Shephard, Elizabeth A; Chandan, Pritpal; Stevanovic-Walker, Milena; Edwards, Mina; Phillips, Ian R

    2007-09-15

    In humans, expression of the FMO1 (flavin-containing mono-oxygenase 1) gene is silenced postnatally in liver, but not kidney. In adult mouse, however, the gene is active in both tissues. We investigated the basis of this species-dependent tissue-specific transcription of FMO1. Our results indicate the use of three alternative promoters. Transcription of the gene in fetal human and adult mouse liver is exclusively from the P0 promoter, whereas in extra-hepatic tissues of both species, P1 and P2 are active. Reporter gene assays showed that the proximal P0 promoters of human (hFMO1) and mouse (mFmo1) genes are equally effective. However, sequences upstream (-2955 to -506) of the proximal P0 of mFmo1 increased reporter gene activity 3-fold, whereas hFMO1 upstream sequences (-3027 to -541) decreased reporter gene activity by 75%. Replacement of the upstream sequence of human P0 with the upstream sequence of mouse P0 increased activity of the human proximal P0 8-fold. Species-specific repetitive elements are present immediately upstream of the proximal P0 promoters. The human gene contains five LINE (long-interspersed nuclear element)-1-like elements, whereas the mouse gene contains a poly A region, an 80-bp direct repeat, an LTR (long terminal repeat), a SINE (short-interspersed nuclear element) and a poly T tract. The rat and rabbit FMO1 genes, which are expressed in adult liver, lack some (rat) or all (rabbit) of the elements upstream of mouse P0. Thus silencing of FMO1 in adult human liver is due apparently to the presence upstream of the proximal P0 of L1 (LINE-1) elements rather than the absence of retrotransposons similar to those found in the mouse gene.

  17. [Arthroscopic fracture management in proximal humeral fractures].

    Science.gov (United States)

    Lill, H; Katthagen, C; Jensen, G; Voigt, C

    2013-04-01

    Arthroscopy has become increasingly more established in the treatment of proximal humeral fractures. In addition to the known advantages of minimally invasive surgery fracture and implant positioning can be optimized and controlled arthroscopically and relevant intra-articular concomitant pathologies (e.g. biceps tendon complex and rotator cuff) can be diagnosed and treated. Arthroscopic techniques have proven to be advantageous in the treatment of various entities of greater tuberosity fractures, lesser tuberosity fractures (suture bridging technique) and subcapital humeral fractures (arthroscopic nailing). This article presents an overview on innovative arthroscopic modalities for treating proximal humeral fractures, describes the surgical techniques and the advantages compared to open procedures as well as initial clinical results.

  18. SINA: A test system for proximity fuses

    Science.gov (United States)

    Ruizenaar, M. G. A.

    1989-04-01

    SINA, a signal generator that can be used for testing proximity fuses, is described. The circuitry of proximity fuses is presented; the output signal of the RF circuit results from a mixing of the emitted signal and received signal that is Doppler shifted in frequency by the relative motion of the fuse with respect to the reflecting target of surface. With SINA, digitized and stored target and clutter signals (previously measured) can be transformed to Doppler signals, for example during a real flight. SINA can be used for testing fuse circuitry, for example in the verification of results of computer simulations of the low frequency Doppler signal processing. The software of SINA and its use are explained.

  19. Tunable Magnetic Proximity Effects in Graphene Junctions

    Science.gov (United States)

    Lazic, Predrag; Belashchenko, Kirill; Zutic, Igor

    2015-03-01

    The characteristic length of the magnetic proximity effects exceed the thickness of a graphene layer leading to an important, but typically overlooked, modifications of equilibrium and transport properties, as well as the implications for graphene spintronics. Using the first-principles studies that integrate a real space density functional theory (GPAW) with the state-of-the art boundary elements electrostatic code based on the Robin Hood method, we explore tunable electronic structure and magnetic proximity effects in the ferromagnet/insulator/graphene junctions. We show that the inclusion of a finite-size gate electrodes and van der Walls interaction lead to nontrivial effects that could also be important in other two-dimensional materials beyond graphene. Work supported by US ONR, NSF-DMR and Nebraska NSF MRSEC.

  20. Management of Proximal Third Arm Replantation

    Directory of Open Access Journals (Sweden)

    Süleyman Taş

    2017-12-01

    Full Text Available Notwithstanding the recent success in major limb replantation achieved through the advancements in microsurgical techniques, the viability of the extremity is still relatively low at the transhumeral level following a replantation. There are no exact guidelines for deciding whether to undertake a stump repair or a replantation in such amputations at the proximal level. However, a highly motivated patient with realistic expectations and protected shoulder function can be a candidate to undergo replantation. The replanted arm may help the uninjured arm in daily activities. In this report we present the case of a 47-year-old man whose arm was amputated at proximal third level by an asphalt machine and successfully replanted together with the encountered problems and their solutions. The roadmap followed in this rare case may be a guide for hand surgeons.

  1. Dedifferentiated chondrosarcoma of right proximal femur

    Directory of Open Access Journals (Sweden)

    Sachin A Badge

    2016-01-01

    Full Text Available Dedifferentiated chondrosarcoma (DDCS comprises approximately 10% of all chondrosarcomas. The tumor generally occurs after the age of 50 years, with equal distribution among males and females. It is most often located in the bones of the pelvis, the proximal femur or humerus, the distal femur, and the ribs. Regardless of treatment, the prognosis is ominous with 90% of patients dying with distant metastases within 2 years. We report a case of DDCS of right proximal femur in a 73-year-old woman. The most important factors affecting survival are early recognition of the radiographic features, adequate histological sampling, and wide-margin resection of the lesion. So for the correct histopathological diagnosis the biopsy sample should be adequate to visualize both cartilaginous and noncartilaginous sarcomatous component which helps to increase the survival of patients before the distant metastasis occurs.

  2. Comparative analysis of tandem T7-like promoter containing regions in enterobacterial genomes reveals a novel group of genetic islands | Center for Cancer Research

    Science.gov (United States)

    Twelve prophage-like T7 islands have been discovered in pathogenic bacterial genomes. These islands contain two or three tandem T7-like promoters that should be activated when a bacterial cell is infected by bacteriophage T7 or a related phage. The illustration shows genetic maps for four of the islands, Ty2, BS512, E22 and ECA, which are found in the genomes of S. enterica Ty2, S. boydii BS512, E. coli E22 and E. carotovora SCRI1043 respectively.

  3. The Impact of Proximity to Urban Center on Crop Production Choice ...

    African Journals Online (AJOL)

    This article attempts to demonstrate how proximity to urban centers influences households' decision to allot their agricultural land to the production of either staple crops or high value cash crops. By applying fractional logit estimation technique on data collected from villages in Wollo of the Amhara Regional State in 2006, ...

  4. Case report A Rare Cause of Sub-Acute Proximal Intestinal ...

    African Journals Online (AJOL)

    KIGZ

    A Rare Cause of Sub-Acute Proximal Intestinal Obstruction Due to Annular Pancreas. Weledji EP, Ngowe M, Mokake M. Department of Surgery, Regional Hospital Buea, Cameroon. Correspondence to: E P Weledji, P.O Box 126, Limbe, Cameroon. Email:elroypat@yahoo.co.uk. Summary. Background: Annular pancreas is a ...

  5. Management of Acute Proximal Humeral Fractures.

    Science.gov (United States)

    Kancherla, Vamsi Krishna; Singh, Anshuman; Anakwenze, Oke A

    2017-01-01

    Proximal humeral fractures, which typically occur in elderly persons, are among the most common fractures. A myriad of nonsurgical and surgical treatment options exist for these injuries, including short-term immobilization and early physical therapy, percutaneous fixation, plate osteosynthesis, intramedullary nailing, hemiarthroplasty, and reverse shoulder arthroplasty. The choice of treatment depends on the fracture type and severity, surgeon expertise, patient age, and patient health status.

  6. Superconducting proximity effect in clean ferromagnetic layers

    OpenAIRE

    Zareyan, M.; Belzig, W.; Nazarov, Yu. V.

    2002-01-01

    We investigate the superconducting proximity effect in clean ferromagnetic layers with rough boundaries. The subgap density of states is formed by Andreev bound states at energies which depend on trajectory length and the ferromagnetic exchange field. At energies above the gap, the spectrum is governed by resonant scattering states. The resulting density of states, measurable by tunneling spectroscopy, exhibits a rich structure, which allows us to connect the theoretical parameters from exper...

  7. Alternating proximal algorithm for blind image recovery

    OpenAIRE

    Bolte, Jérôme; Combettes, Patrick Louis; Pesquet, Jean-Christophe

    2010-01-01

    International audience; We consider a variational formulation of blind image recovery problems. A novel iterative proximal algorithm is proposed to solve the associated nonconvex minimization problem. Under suitable assumptions, this algorithm is shown to have better convergence properties than standard alternating minimization techniques. The objective function includes a smooth convex data fidelity term and nonsmooth convex regularization terms modeling prior information on the data and on ...

  8. Isolated Proximal Tibiofibular Dislocation during Soccer

    Directory of Open Access Journals (Sweden)

    Casey Chiu

    2015-01-01

    Full Text Available Proximal tibiofibular dislocations are rarely encountered in the Emergency Department (ED. We present a case involving a man presenting to the ED with left knee pain after making a sharp left turn on the soccer field. His physical exam was only remarkable for tenderness over the lateral fibular head. His X-rays showed subtle abnormalities of the tibiofibular joint. The dislocation was reduced and the patient was discharged from the ED with orthopedic follow-up.