WorldWideScience

Sample records for synthesis initiation factors

  1. Protein Synthesis Initiation Factors: Phosphorylation and Regulation

    Energy Technology Data Exchange (ETDEWEB)

    Karen S. Browning

    2009-06-15

    The initiation of the synthesis of proteins is a fundamental process shared by all living organisms. Each organism has both shared and unique mechanisms for regulation of this vital process. Higher plants provide for a major amount of fixation of carbon from the environment and turn this carbon into food and fuel sources for our use. However, we have very little understanding of how plants regulate the synthesis of the proteins necessary for these metabolic processes. The research carried out during the grant period sought to address some of these unknowns in the regulation of protein synthesis initiation. Our first goal was to determine if phosphorylation plays a significant role in plant initiation of protein synthesis. The role of phosphorylation, although well documented in mammalian protein synthesis regulation, is not well studied in plants. We showed that several of the factors necessary for the initiation of protein synthesis were targets of plant casein kinase and showed differential phosphorylation by the plant specific isoforms of this kinase. In addition, we identified and confirmed the phosphorylation sites in five of the plant initiation factors. Further, we showed that phosphorylation of one of these factors, eIF5, affected the ability of the factor to participate in the initiation process. Our second goal was to develop a method to make initiation factor 3 (eIF3) using recombinant methods. To date, we successfully cloned and expressed 13/13 subunits of wheat eIF3 in E. coli using de novo gene construction methods. The final step in this process is to place the subunits into three different plasmid operons for co-expression. Successful completion of expression of eIF3 will be an invaluable tool to the plant translation community.

  2. Role of Protein Synthesis Initiation Factors in Dietary Soy Isoflavone-Mediated Effects on Breast Cancer Progression

    Science.gov (United States)

    2013-03-01

    Tumor Model—The tumors were derived from our previous study (30). Briefly, female athymic nu/nu mice, 5 weeks old ( Charles River Laboratories...Jopling, C. L., Dickens , M., MacFarlane, M., and Willis, A. E. (2000) c-Myc protein synthesis is initiated from the in- ternal ribosome entry segment

  3. Synthesis of the ICT4RED initiative

    CSIR Research Space (South Africa)

    Herselman, M

    2014-12-01

    Full Text Available This section will provide a synthesis of the ICT4RED initiative and will highlight certain important elements of success. It will re-address the aims and objectives which were provided in Section 1 and also address some significant changes which...

  4. Architecture of human translation initiation factor 3

    Science.gov (United States)

    Querol-Audi, Jordi; Sun, Chaomin; Vogan, Jacob M.; Smith, Duane; Gu, Yu; Cate, Jamie; Nogales, Eva

    2013-01-01

    SUMMARY Eukaryotic translation initiation factor 3 (eIF3) plays a central role in protein synthesis by organizing the formation of the 43S preinitiation complex. Using genetic tag visualization by electron microscopy, we reveal the molecular organization of ten human eIF3 subunits, including an octameric core. The structure of eIF3 bears a close resemblance to that of the proteasome lid, with a conserved spatial organization of eight core subunits containing PCI and MPN domains that coordinate functional interactions in both complexes. We further show that eIF3 subunits a and c interact with initiation factors eIF1 and eIF1A, which control the stringency of start codon selection. Finally, we find that subunit j, which modulates messenger RNA interactions with the small ribosomal subunit, makes multiple independent interactions with the eIF3 octameric core. These results highlight the conserved architecture of eIF3 and how it scaffolds key factors that control translation initiation in higher eukaryotes, including humans. PMID:23623729

  5. Risk Factors Associated With Sustaining a Sport-related Concussion: An Initial Synthesis Study of 12,320 Student-Athletes.

    Science.gov (United States)

    Brett, Benjamin L; Kuhn, Andrew W; Yengo-Kahn, Aaron M; Solomon, Gary S; Zuckerman, Scott L

    2018-02-17

    The empirical identification of risk factors associated with sport-related concussion (SRC) may improve the management of student-athletes. The current study attempted to identify and quantify bio-cognitive risk factors associated with sustaining a SRC. Cross-sectional ambispective study; level of evidence, 3. Neurocognitive testing of 12,320 middle school, high school and collegiate athletes was completed at preseason baseline and post-SRC. Univariate and multivariable logistic regressions were used to determine which pre-injury variables accurately predicted the occurrence of SRC. A quantitative risk score for each variable was developed. Five of 13 variables maintained significance in the multivariable model with the associated weighted point scores: SRC history (21), prior headache treatment (6), contact sport (5), youth level of play (7), and history of ADHD/LD (2). Six stratified groups were formed based on probability of SRC, which produced an area under the curve (AUC) of 0.71 (95% CI 0.69-0.72, p < .001). Though the model was a significant predictor of SRC (X2 = 1,112.75, p < .001), the effect size was small and accounted for only 16% of the overall variance. An initial aggregate model of weighted bio-cognitive factors associated with increased odds of sustaining a SRC was developed. Previously validated factors were confirmed, yet a large source of variance remained unexplained. These findings emphasize the need to expand the host factors studied when assessing SRC risk, and that the existing, empirically based bio-cognitive factors do not adequately quantify the risk of SRC.

  6. Climate change initiatives of state departments of transportation : synthesis

    Science.gov (United States)

    2008-01-01

    The WSDOT Public Transportation Division Director requested a synthesis report on the role of state departments of transportation in climate change initiatives. A search of available information has revealed a host of measures underway to reduce gree...

  7. Initiation of protein synthesis in bacteria

    DEFF Research Database (Denmark)

    Laursen, Brian Søgaard; Sørensen, Hans Peter; Mortensen, Kim Kusk

    2005-01-01

    Valuable information on translation initiation is available from biochemical data and recently solved structures. We present a detailed description of current knowledge about the structure, function, and interactions of the individual components involved in bacterial translation initiation. The f...

  8. Starting the protein synthesis machine: eukaryotic translation initiation.

    Science.gov (United States)

    Preiss, Thomas; W Hentze, Matthias

    2003-12-01

    The final assembly of the protein synthesis machinery occurs during translation initiation. This delicate process involves both ends of eukaryotic messenger RNAs as well as multiple sequential protein-RNA and protein-protein interactions. As is expected from its critical position in the gene expression pathway between the transcriptome and the proteome, translation initiation is a selective and highly regulated process. This synopsis summarises the current status of the field and identifies intriguing open questions. Copyright 2003 Wiley Periodicals, Inc.

  9. Heterogeneous Pathways and Timing of Factor Departure during Translation Initiation

    Science.gov (United States)

    Tsai, Albert; Petrov, Alexey; Marshall, R. Andrew; Korlach, Jonas; Uemura, Sotaro; Puglisi, Joseph D.

    2015-01-01

    Initiation of translation establishes the reading frame for protein synthesis and is a key point of regulation1. Initiation involves factor-driven assembly at a start codon of an mRNA of an elongation competent 70S ribosomal particle (in bacteria) from separated 30S and 50S subunits and initiator tRNA. Here we establish by direct single-molecule tracking the timing of initiator tRNA, initiation factor 2 (IF2), and 50S subunit joining during initiation. Our results show multiple pathways to initiation, with orders of arrival of tRNA and IF2 dependent on factor concentration and composition. IF2 accelerates 50S subunit joining, and stabilizes the assembled 70S complex. Transition to elongation is gated by the departure of IF2 after GTP hydrolysis, allowing efficient arrival of elongator tRNAs to the second codon presented in the aminoacyl-tRNA acceptor site. These experiments highlight the power of single-molecule approaches to delineate mechanism in complex multicomponent systems. PMID:22722848

  10. Maternal obesity, psychological factors, and breastfeeding initiation.

    Science.gov (United States)

    Mehta, Ushma J; Siega-Riz, Anna Maria; Herring, Amy H; Adair, Linda S; Bentley, Margaret E

    2011-12-01

    Maternal obesity has been associated with lower initiation of breastfeeding, but reasons for why this association exists have not been well studied. In this study, we examined associations among prepregnancy obesity, psychological factors during pregnancy, and breastfeeding initiation. Data came from the postpartum component of the Pregnancy, Infection, and Nutrition study, a prospective cohort study. Pregnant women were recruited from the University of North Carolina hospitals between January 2001 and June 2005. This analysis used data from 688 women followed from pregnancy to 3 months postpartum. Multivariable binomial regression was used to determine the association between having a body mass index (BMI) >26 kg/m(2) before pregnancy and breastfeeding initiation. We tested for mediation of the association between pregravid BMI and breastfeeding initiation by certain psychological factors during pregnancy (depressive symptoms, perceived stress, anxiety, and self-esteem). Women who began pregnancy overweight or obese (BMI >26 kg/m(2)) had almost four times the risk of not initiating breastfeeding compared with underweight or normal weight women (BMI ≤26 kg/m(2)) (risk ratio = 3.94 [95% confidence interval 2.17, 7.18]) after adjusting for race, poverty level, education level, and marital status. Depressive symptoms, perceived stress, anxiety, and self-esteem levels during pregnancy were not found to mediate the association between pregravid BMI and breastfeeding initiation. Women who started pregnancy either overweight or obese were more likely to not initiate breastfeeding. Contrary to expectations, pregnancy-related psychological factors did not influence this relationship.

  11. Initiation factor 2, tRNA, and 50S subunits cooperatively stabilize mRNAs on the ribosome during initiation

    Science.gov (United States)

    Masuda, Tomoaki; Petrov, Alexey N.; Iizuka, Ryo; Funatsu, Takashi; Puglisi, Joseph D.; Uemura, Sotaro

    2012-01-01

    Initiation factor 2 (IF2) is a key factor in initiation of bacterial protein synthesis. It recruits initiator tRNA to the small ribosomal subunit and facilitates joining of the large ribosomal subunit. Using reconstituted translation system of Escherichia coli and optical tweezers, we directly measure the rupture force between single ribosomal complexes and mRNAs for initiation complexes in the presence and the absence of IF2. We demonstrate that IF2 together with codon recognition by initiator tRNA increases the force required to dislocate mRNA from the ribosome complexes; mRNA stabilization by IF2 required the presence of a joined 50S subunit, and was independent of bound guanine nucleotide. IF2 thus helps lock the 70S ribosome over the start codon during initiation, thus maintaining reading frame. Our results show how mRNA is progressively stabilized on the ribosome through distinct steps of initiation. PMID:22411833

  12. Phosphorylation Stoichiometries of Human Eukaryotic Initiation Factors

    Directory of Open Access Journals (Sweden)

    Armann Andaya

    2014-06-01

    Full Text Available Eukaryotic translation initiation factors are the principal molecular effectors regulating the process converting nucleic acid to functional protein. Commonly referred to as eIFs (eukaryotic initiation factors, this suite of proteins is comprised of at least 25 individual subunits that function in a coordinated, regulated, manner during mRNA translation. Multiple facets of eIF regulation have yet to be elucidated; however, many of the necessary protein factors are phosphorylated. Herein, we have isolated, identified and quantified phosphosites from eIF2, eIF3, and eIF4G generated from log phase grown HeLa cell lysates. Our investigation is the first study to globally quantify eIF phosphosites and illustrates differences in abundance of phosphorylation between the residues of each factor. Thus, identification of those phosphosites that exhibit either high or low levels of phosphorylation under log phase growing conditions may aid researchers to concentrate their investigative efforts to specific phosphosites that potentially harbor important regulatory mechanisms germane to mRNA translation.

  13. SYNTHESIS OF STYRENE-BUTADIENE STATISTIC COPOLYMERS CONTAINING MAGNESIUM INITIATOR

    Directory of Open Access Journals (Sweden)

    A. V. Firsova

    2015-01-01

    Full Text Available The article discusses the use of organomagnesium initiators in the synthesis of styrene-butadiene random copolymer (SBR obtained solution polymerization and their influence on the properties of rubber. Selected organic magnesium dialkyl initiator is combined with a modifier, which is a mixed alkoxide of an alkali and alkaline earth metals, which allows to control the micr ostructure of the diene polymer and its molecular weight characteristics. Alcohol derivatives selected high-boiling alcohols tetra (hydroxypropyl ethylenediamine (lapromol 294 and tetrahydrofurfuryl alcohol (TGFS. Selection of high-boiling alcohols due to the fact that the destruction of alkoxide with aqueous polymer degassing they do not fall into the return solvent and almost fall into the exact water. The metal components of alkoxides are lithium, sodium, potassium, magnesium and calcium. The resulting solutions are stable when stored modifier t hroughout the year even at -40 °C. The scheme of obtaining the new catalyst systems based organomagnesium and alcoxide of alkali and alkaline earth metals, which yields as functionalized SBR with a statistical and a distribution block of butadiene and styrene was developed. The process of copolymerization with styrene to butadiene organomagnesium initiators as using an organolithium compound (n-butyllithium was carried out, and without it. Found that the addition of n-butyllithium in the reaction mixture leads to a sharp increase in the rate of reaction. The results of studies of the effect of composition of the initiator system on the structure of diene polymers. It was revealed that a mixed initiator system affords a high conversion of monomers (to 90 % in 1 hour 1,2-polybutadiene content increased to 60 %. The process of polymerization of only a mixture of organomagnesium initiators and alcoxide of alkali and alkaline earth metals are not actively proceeds, conversion of the monomers reaches to 90 % in 4 hours, the microstructure

  14. Recent advances in microwave initiated synthesis of nanocarbon materials

    Science.gov (United States)

    Zhang, Xinyu; Liu, Zhen

    2012-01-01

    This Feature Article focuses on the recent advances in synthesis of nanostructured carbon materials using microwave irradiation as the heating source. Although the microwave approach to chemical synthesis is relatively mature in organic synthesis, it is still in the early stage for nanomaterials synthesis, especially nanocarbons. Due to the energy efficient nature of microwave heating, there is a great opportunity to apply microwave irradiation to nanocarbon production, which normally requires high temperature, high vacuum or inert gas protections. Using microwave irradiation will give a green feature to the nanocarbon synthesis, since it offers high efficiency heating and fast carbonization. With our recent discovery, multi-walled carbon nanotubes can be synthesized through the microwave process even in air. Background about nanocarbons and microwave chemistry are introduced, the application of microwaves in synthesis of different types of nanocarbons is discussed and finally, the perspectives in the future research directions of microwave assisted nanocarbon synthesis are deliberated as well.

  15. Synthesis of amphiphilic copolymers by ATRP initiated with a bifunctional initiator containing trichlomethyl groups

    Czech Academy of Sciences Publication Activity Database

    Ritz, Pavel; Látalová, Petra; Janata, Miroslav; Toman, Luděk; Kříž, Jaroslav; Genzer, J.; Vlček, Petr

    2007-01-01

    Roč. 67, č. 10 (2007), s. 1027-1039 ISSN 1381-5148 R&D Projects: GA MŠk 1P05ME753 Institutional research plan: CEZ:AV0Z40500505 Keywords : ATRP * block copolymer * polyhalogenated initiator * amphiphilic copolymer Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.720, year: 2007

  16. Towards a Classification of Architecture Initiatives: Outlining the External Factors

    DEFF Research Database (Denmark)

    Hansen, Christian Lindschou; Mortensen, Niels Henrik; Hvam, Lars

    2012-01-01

    or bad, without including the contextual differences. The purpose of the external factors is to improve scoping and goal setting of architecture initiatives, and improve comparability between- and transferability of knowledge from architecture initiatives. The external factors are a first step towards...

  17. Protein synthesis during the initial phase of the temperature-induced bleaching response in Euglena gracilis

    International Nuclear Information System (INIS)

    Ortiz, W.

    1990-01-01

    Growing cultures of photoheterotrophic Euglena gracilis experience an increase in chlorophyll accumulation during the initial phase of the temperature-induced bleaching response suggesting an increase in the synthesis of plastid components at the bleaching temperature of 33 degree C. A primary goal of this work was to establish whether an increase in the synthesis of plastid proteins accompanies the observed increase in chlorophyll accumulation. In vivo pulse-labeling experiments with [ 35 S]sodium sulfate were carried out with cells grown at room temperature or at 33 degree C. The synthesis of a number of plastid polypeptides of nucleocytoplasmic origin, including some presumably novel polypeptides, increased in cultures treated for 15 hours at 33 degree C. In contrast, while synthesis of thylakoid proteins by the plastid protein synthesis machinery decreased modestly, synthesis of the large subunit of the enzyme ribulosebisphosphate carboxylase was strongly affected at the elevated temperature. Synthesis of novel plastid-encoded polypeptides was not induced at the bleaching temperature. It is concluded that protein synthesis in plastids declines during the initial phase of the temperature response in Euglena despite an overall increase in cellular protein synthesis and an increase in chlorophyll accumulation per cell

  18. Phosphorylation in vitro of eukaryotic initiation factors IF-E2 and IF-E3 by protein kinases

    DEFF Research Database (Denmark)

    Issinger, O G; Benne, R; Hershey, J W

    1976-01-01

    Purified protein synthesis initiation factors IF-E2 and IF-E3 from rabbit reticulocytes were phosphorylated in vitro with protein kinases isolated from the same source. The highest levels of phosphorylation resulted from incubation of the factors with a cyclic nucleotide-independent protein kinase...

  19. Magnitude and factors associated with delayed initiation of ...

    African Journals Online (AJOL)

    Background: Breastfeeding as a determinant of infant health and nutrition saves up to 1.5 million infant lives annually. Though breastfeeding is mostly universal in sub-Saharan Africa, early initiation of breastfeeding is rarely practiced. Objective: To determine magnitude and factors associated with delayed initiation of ...

  20. Factors predicting the initiation of prenatal care in Mexican women.

    Science.gov (United States)

    Quelopana, Ana M; Champion, Jane Dimmitt; Salazar, Bertha C

    2009-06-01

    to describe factors related to the initiation of prenatal care (PNC) among pregnant Mexican women. descriptive correlational. public prenatal clinic in Monterrey, Mexico. 253 pregnant Mexican women aged 13-46 years. structured interviews were conducted to obtain information concerning demographics, reproductive history, current pregnancy, perceptions of benefits and barriers of PNC, negative attitudes towards pregnancy and social support. Late initiation of PNC was reported by 47% of participants. Factors related to PNC initiation were education, perceived benefits or barriers, and negative attitudes towards pregnancy. Women who initiated PNC at an early stage were more likely to live with a partner, had a higher educational level and anticipated desirable personal benefits of PNC. Perceptions of barriers to PNC impeded early initiation of care. Social support did not influence PNC initiation. Negative attitudes towards pregnancy increased the likelihood of late PNC initiation. screening for negative attitudes towards pregnancy, partner status, educational level and perceived health-care barriers among pregnant Mexican women is important. Health-care providers may then address these psychosocial risk factors through PNC interventions promoting early initiation of care.

  1. Signals for the initiation and termination of synthesis of the viral strand of bacteriophage f1

    International Nuclear Information System (INIS)

    Dotto, G.P.; Horiuchi, K.; Jakes, K.S.; Zinder, N.D.

    1983-01-01

    In this paper the sequence around the plus origin that is required for efficient plus-strand synthesis as well as that necessary for gene-II-protein recognition is described. Results which demonstrate that the nucleotide sequence of the f1 plus origin contains two overlapping but distinct signals, one for initiation and the other for termination of plus-strand synthesis is presented. 29 references, 6 figures, 1 table

  2. Factors Associated with Early Smoking Initiation among Korean Adolescents

    Directory of Open Access Journals (Sweden)

    Eun Sun So, PhD

    2015-06-01

    Conclusions: Interventions targeting the prevention of smoking initiation among adolescents should include individual factors such as health status, body weight, perceived mental health status, health-risk behaviors, and academic characteristics as well as family factors that reinforce family cohesion and home smoking bans. Moreover, male adolescents aged 12–13 years and their parents should be the main target of these interventions.

  3. Origins of robustness in translational control via eukaryotic translation initiation factor (eIF) 2.

    Science.gov (United States)

    Khan, Mohammad Farhan; Spurgeon, Sarah; von der Haar, Tobias

    2018-05-14

    Phosphorylation of eukaryotic translation initiation factor 2 (eIF2) is one of the best studied and most widely used means for regulating protein synthesis activity in eukaryotic cells. This pathway regulates protein synthesis in response to stresses, viral infections, and nutrient depletion, among others. We present analyses of an ordinary differential equation-based model of this pathway, which aim to identify its principal robustness-conferring features. Our analyses indicate that robustness is a distributed property, rather than arising from the properties of any one individual pathway species. However, robustness-conferring properties are unevenly distributed between the different species, and we identify a guanine nucleotide dissociation inhibitor (GDI) complex as a species that likely contributes strongly to the robustness of the pathway. Our analyses make further predictions on the dynamic response to different types of kinases that impinge on eIF2. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Synthesis and Characterization of New Surface Active Azo Initiators for Radical Reactions

    Directory of Open Access Journals (Sweden)

    Klaus Tauer

    2000-04-01

    Full Text Available The synthesis of a water soluble azo initiators from 2,2’-azodiisobutyronitrile (AIBN was performed in three steps: reaction of dinitrile with aromatic alcohols in the presence of HCl to form bisiminoesters hydrochlorides which are hydrolyzed to the esters and final regioselective sulfonation of the aromatic esters. The thermal decomposition of the azo initiators obtained leads to formation of two surface active radicals which can start the chain reaction.

  5. Initiation signals for complementary strand DNA synthesis on single-stranded plasmid DNA

    NARCIS (Netherlands)

    van der Ende, A.; Teertstra, R.; van der Avoort, H. G.; Weisbeek, P. J.

    1983-01-01

    The bacteriophage 0X174 origin for (+) strand DNA synthesis, when inserted in a plasmid, is in vivo a substrate for the initiator A protein, that is produced by infecting phages. The result of this interaction is the packaging of single-stranded plasmid DNA into preformed phage coats. These plasmid

  6. Magnitude and factors associated with delayed initiation of ...

    African Journals Online (AJOL)

    reasons were perceived lack of breast milk, need of rest for both mother and baby after labor, and negative cultural beliefs. .... Frequency of antenatal care attendance ... skin practice. African Health Sciences Vol 15 Issue 4, December 2015. Table 3 shows that factors independently associated with delayed initiation of ...

  7. The effect of heat and radiation on the initiation and elongation processes of DNA synthesis

    International Nuclear Information System (INIS)

    Davies, R.C.; Bowden, G.T.; Cress, A.E.

    1983-01-01

    The pH step alkaline elution and alkaline sucrose gradient techniques were utilized to evaluate alterations in DNA replication (initiation and elongation) induced by heat and low dose X-irradiation in synchronized Chinese hamster ovary cells. The initiation and elongation processes of DNA synthesis were radioresistant at the G 1 /S boundary (4 hours after mitosis) while in mid S phase (9 hours after mitosis) DNA initiation and elongation were sensitive to X-irradiation. The initiation and elongation processes of DNA synthesis which were radiation resistant at the G 1 /S boundary could be inhibited by a hyperthermia treatment (43 0 C for 1 hour beginning at 4 hours after mitosis). The impairment of initiation in the heated cells was maintained through late S phase while that of elongation was reversible as judged by full recovery at 15 hours after mitosis. These data suggest that the known synergistic lethality of heat and radiation may be mediated by an impairment of initiation of DNA synthesis. (author)

  8. The experience of initiating injection drug use and its social context: a qualitative systematic review and thematic synthesis.

    Science.gov (United States)

    Guise, Andy; Horyniak, Danielle; Melo, Jason; McNeil, Ryan; Werb, Dan

    2017-12-01

    Understanding the experience of initiating injection drug use and its social contexts is crucial to inform efforts to prevent transitions into this mode of drug consumption and support harm reduction. We reviewed and synthesized existing qualitative scientific literature systematically to identify the socio-structural contexts for, and experiences of, the initiation of injection drug use. We searched six databases (Medline, Embase, PsychINFO, CINAHL, IBSS and SSCI) systematically, along with a manual search, including key journals and subject experts. Peer-reviewed studies were included if they qualitatively explored experiences of or socio-structural contexts for injection drug use initiation. A thematic synthesis approach was used to identify descriptive and analytical themes throughout studies. From 1731 initial results, 41 studies reporting data from 1996 participants were included. We developed eight descriptive themes and two analytical (higher-order) themes. The first analytical theme focused on injecting initiation resulting from a social process enabled and constrained by socio-structural factors: social networks and individual interactions, socialization into drug-using identities and choices enabled and constrained by social context all combine to produce processes of injection initiation. The second analytical theme addressed pathways that explore varying meanings attached to injection initiation and how they link to social context: seeking pleasure, responses to increasing tolerance to drugs, securing belonging and identity and coping with pain and trauma. Qualitative research shows that injection drug use initiation has varying and distinct meanings for individuals involved and is a dynamic process shaped by social and structural factors. Interventions should therefore respond to the socio-structural influences on injecting drug use initiation by seeking to modify the contexts for initiation, rather than solely prioritizing the reduction of individual

  9. Curcumin modulates eukaryotic initiation factors in human lung adenocarcinoma epithelial cells.

    Science.gov (United States)

    Chen, Lixia; Tian, Guoqing; Shao, Changxia; Cobos, Everardo; Gao, Weimin

    2010-10-01

    Curcumin, a polyphenolic compound, is the active component of Curcuma longa and has been extensively investigated as an anticancer drug that modulates multiple pathways. Eukaryotic initiation factors (eIFs) have been known to play important roles in translation initiation, which controls cell growth and proliferation. Little is known about the effects of curcumin on eIFs in lung cancer. The objective of this study was to exam the curcumin cytotoxic effect and modulation of two major rate-limiting translation initiation factors, including eIF2α and eIF4E protein expression levels in lung adenocarcinoma epithelial cell line A549. Cytotoxicity was measured by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and protein changes were determined by Western blot. A549 cells were treated with 0-240 μM curcumin for 4-96 h. The inhibitory effects of curcumin on cytotoxicity were dose- and time-dependent (P cells were treated with 20 and 40 μM curcumin for 24 h. In addition, the effects of curcumin on these protein expression changes followed a significant dose-response (P cell viability through prohibiting the initiation of protein synthesis by modulating eIF2α and eIF4E.

  10. [Cigarette smoking initiation among Tunisian adolescents: Risk and protective factors].

    Science.gov (United States)

    Fakhfakh, R; Jaidane, I; Hsairi, M; Ben Hamida, A M

    2015-12-01

    Since smoking is a major public health problem among Tunisian teenagers, it is important to identify the underlying risk and protective factors associated with initiation of this behavior. A cross-sectional, school-based survey of students was conducted by the Tunisian Ministry of Health among a nationally representative sample of 4172 adolescents aged between 12 and 20 years attending public, private, and professional secondary schools across Tunisia who participated in the Survey of the Health of Tunisian adolescents in 2000. For data analysis, we first calculated crude odds ratios (OR) followed by calculating adjusted OR after using multivariate logistic regression models. Almost one-third of respondents had already started smoking at an average age of 13 years, 6.4% among them smoked daily. Demographic vulnerabilities to smoking behavior were gender (boys more than girls), age and residence in urban areas and particularly in Greater Tunis and the North East. Familial and school factors were parental divorce, poor relationship with parents, poor integration into the peer group, and poor school investment. Psychological and behavioral factors were low self-esteem level and the occurrence of stressful life events, risk taking and alcohol consumption when there was no association with the depression, anxiety and body image. Protective factors against the experimental cigarettes were mainly sports and reading. There are many factors associated with smoking behavior among adolescents. All of these predictors need to be considered in smoking prevention among Tunisian teenagers. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  11. Injuries, risk factors and prevention initiatives in youth sport.

    Science.gov (United States)

    Frisch, Anne; Croisier, Jean-Louis; Urhausen, Axel; Seil, Romain; Theisen, Daniel

    2009-01-01

    Sports injuries in young athletes are a public health issue which deserves special attention. Effective prevention can be achieved with training programmes originating from the field of physical therapy and medicine. A systematic literature search on injury prevention in youth sport was performed in the MEDLINE database. For prevention programmes to reduce sports injuries, critical factors must be considered, such as training content, duration and frequency, as well as athlete compliance. Home-based programmes could be inferior to supervised training, but are efficient if compliance is high. So far prevention programmes have focused on team sports and their efficiency in individual sports remains to be proven. Active prevention programmes focusing specifically on the upper extremity are scarce. Initiatives enhancing the awareness of trainers, athletes and therapists about risk factors and systematic prevention measures should be encouraged.

  12. Factors influencing initiation and duration of breast feeding in Ireland.

    LENUS (Irish Health Repository)

    Leahy-Warren, Patricia

    2013-03-05

    The aim of this research was to identify factors associated with mothers breast feeding and to identify, for those who breast fed, factors associated with breast feeding for as long as planned. BACKGROUND: breast-feeding rates in Ireland are amongst the lowest in Europe. Research evidence indicates that in order for mothers to be successful at breast feeding, multiplicities of supports are necessary for both initiation and duration. The nature of these supports in tandem with other influencing factors requires analysis from an Irish perspective. DESIGN: cross-sectional study involving public health nurses and mothers in Ireland. This paper presents the results of the mothers\\' evaluation. METHOD: mothers (n=1715) with children less than three years were offered a choice of completing the self-report questionnaires online or by mail. Data were analysed and reported using descriptive and inferential statistics. FINDINGS: four in every five participants breast fed their infant and two thirds of them breast fed as long as planned. The multivariate logistic regression analysis identified that third level education, being a first time mother or previously having breast fed, participating online, having more than two public health nurse visits, and having a positive infant feeding attitude were independently and statistically significantly associated with breast feeding. Among mothers who breast fed, being aged at least 35 years, participating online, having a positive infant feeding attitude and high breast-feeding self-efficacy were independently and statistically significantly associated with breast feeding for as long as planned. CONCLUSIONS: findings from this study reinforce health inequalities therefore there needs to be a renewed commitment to reducing health inequalities in relation to breast feeding. RELEVANCE TO CLINICAL PRACTICE: this study has identified factors associated with initiation and duration of breast feeding that are potentially modifiable through

  13. Factors influencing initiation and duration of breast feeding in Ireland.

    Science.gov (United States)

    Leahy-Warren, Patricia; Mulcahy, Helen; Phelan, Agnes; Corcoran, Paul

    2014-03-01

    The aim of this research was to identify factors associated with mothers breast feeding and to identify, for those who breast fed, factors associated with breast feeding for as long as planned. breast feeding rates in Ireland are amongst the lowest in Europe. Research evidence indicates that in order for mothers to be successful at breast feeding, multiplicities of supports are necessary for both initiation and duration. The nature of these supports in tandem with other influencing factors requires analysis from an Irish perspective. cross-sectional study involving public health nurses and mothers in Ireland. This paper presents the results of the mothers' evaluation. mothers (n=1715) with children less than three years were offered a choice of completing the self-report questionnaires online or by mail. Data were analysed and reported using descriptive and inferential statistics. four in every five participants breast fed their infant and two thirds of them breast fed as long as planned. The multivariate logistic regression analysis identified that third level education, being a first time mother or previously having breast fed, participating online, having more than two public health nurse visits, and having a positive infant feeding attitude were independently and statistically significantly associated with breast feeding. Among mothers who breast fed, being aged at least 35 years, participating online, having a positive infant feeding attitude and high breast feeding self-efficacy were independently and statistically significantly associated with breast feeding for as long as planned. findings from this study reinforce health inequalities therefore there needs to be a renewed commitment to reducing health inequalities in relation to breast feeding. this study has identified factors associated with initiation and duration of breast feeding that are potentially modifiable through public health interventions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Top Five Physical Design Factors Contributing to Fall Initiation.

    Science.gov (United States)

    Pati, Debajyoti; Lee, Jaehoon; Mihandoust, Sahar; Kazem-Zadeh, Mahshad; Oh, Youngha

    2018-01-01

    To develop a prioritized list of physical design questions/interventions to reduce patient falls by conducting expanded analysis (Phase II) of data generated from a completed study phase. Patient falls continue to be a critical concern for healthcare providers, patients, and families. While substantial literature exist on intrinsic factors, scientific evidence on the role of the physical environment is scarce. Expanded analysis of data from 180 videos of trials conducted in a physical mock-up of a medical-surgical inpatient room in a previously completed study phase. The odds of subject's exhibited postures (predictors) on fall initiation (outcome) were examined in a series of generalized linear mixed effects models. Physical design elements and attributes associated with postures exhibiting statistical significance were examined. Turning, pulling, pushing, and bending forward exhibited the highest odds of contributing to fall initiation in the bathroom. Grabbing, pushing, and sitting exhibited the highest odds of contributing to fall initiation around the patient bed. Physical design elements/attributes associated with the above postures are the (1) bathroom door; (2) bathroom spatial configuration-relative locations of door, toilet bowl, and the sink; (3) door, toilet, and sink hardware; (4) space availability/tightness inside the clinician zone; and (5) spatial configuration around patient bed-relative locations of bed, patient chair, and overbed table, in relation to bathroom door, and resulting obstructions originating from the configuration. Patient falls during unassisted ambulation may be reduced through appropriate examination of these five physical elements/attributes.

  15. Factors Stimulating Internationalisation of Firms: An Attempted Holistic Synthesis

    Directory of Open Access Journals (Sweden)

    Magdalena Belniak

    2015-06-01

    Full Text Available The main goal of this paper is the critical and synthetic analysis of internationalisation process factors, with reference to business management. It presents a systematic review of the most important relational ideas in regard to factors of firm-level internationalisation. The text includes the synthesis of previous academic studies and results of empirical researches on internationalisation factors. The motives for going international are explained in reference to external and internal factors. Different definitions of understanding external factors of internationalisation of firms are discussed, among them (i framework factors (market, cost, governmental, competitive and additional factors, (ii conditioning factors (factor and demand conditions, related and supporting industries, firm strategy, structure and rivalry as well as (iii general environment factors (economic environment, demographic environment, political and legal environment, technological, natural and socio-cultural environment. Internal factors of internationalisation are mostly rooted in the resource-based view. Motives for going international mainly depend on top management team, international resources and firms specifics. The paper underlines that there are numerous factors, both external and internal, which influence international activities of firms. Despite the fact that the decision to internationalize is focused on specific motives and goals, the role of managers is crucial.

  16. Eukaryotic initiation factor 5A dephosphorylation is required for translational arrest in stationary phase cells.

    Science.gov (United States)

    Chung, Janete; Rocha, Antonio A; Tonelli, Renata R; Castilho, Beatriz A; Schenkman, Sergio

    2013-04-15

    The protein known as eIF5A (eukaryotic initiation factor 5A) has an elusive role in translation. It has a unique and essential hypusine modification at a conserved lysine residue in most eukaryotes. In addition, this protein is modified by phosphorylation with unknown functions. In the present study we show that a phosphorylated state of eIF5A predominates in exponentially growing Trypanosoma cruzi cells, and extensive dephosphorylation occurs in cells in stationary phase. Phosphorylation occurs mainly at Ser(2), as shown in yeast eIF5A. In addition, a novel phosphorylation site was identified at Tyr(21). In exponential cells, T. cruzi eIF5A is partially associated with polysomes, compatible with a proposed function as an elongation factor, and becomes relatively enriched in polysomal fractions in stationary phase. Overexpression of the wild-type eIF5A, or eIF5A with Ser(2) replaced by an aspartate residue, but not by alanine, increases the rate of cell proliferation and protein synthesis. However, the presence of an aspartate residue instead of Ser(2) is toxic for cells reaching the stationary phase, which show a less-pronounced protein synthesis arrest and a decreased amount of eIF5A in dense fractions of sucrose gradients. We conclude that eIF5A phosphorylation and dephosphorylation cycles regulate translation according to the growth conditions.

  17. Cryptotanshinone deregulates unfolded protein response and eukaryotic initiation factor signaling in acute lymphoblastic leukemia cells.

    Science.gov (United States)

    Wu, Ching-Fen; Seo, Ean-Jeong; Klauck, Sabine M; Efferth, Thomas

    2016-02-15

    Unfolded protein responses (UPR) determine cell fate and are recognized as anticancer targets. In a previous research, we reported that cryptotanshinone (CPT) exerted cytotoxic effects toward acute lymphoblastic leukemia cells through mitochondria-mediated apoptosis. In the present study, we further investigated the role of UPR in CPT-induced cytotoxicity on acute lymphoblastic leukemia cells by applying tools of pharmacogenomics and bioinformatics. Gene expression profiling was performed by mRNA microarray hybridization. Potential transcription factor binding motifs were identified in the promoter regions of the deregulated genes by Cistrome software. Molecular docking on eIF-4A and PI3K was performed to investigate the inhibitory activity of CPT on translation initiation. CPT regulated genes related to UPR and eIF2 signaling pathways. The DNA-Damage-Inducible Transcript 3 (DDIT3) gene, which is activated as consequence of UPR malfunction during apoptosis, was induced and validated by in vitro experiments. Transcription factor binding motif analysis of the microarrary-retrieved deregulated genes in the promoter region emphasized the relevance of transcription factors, such as ATF2, ATF4 and XBP1, regulating UPR and cell apoptosis. Molecular docking suggested inhibitory effects of CPT by binding to eIF-4A and PI3K providing evidence for a role of CPT's in the disruption of protein synthesis. CPT triggered UPR and inhibited protein synthesis via eIF-mediated translation initiation, potentially supporting CPT-induced cytotoxic effects toward acute leukemia cells. Copyright © 2015 Elsevier GmbH. All rights reserved.

  18. Factors associated with hookah use initiation among adolescents.

    Science.gov (United States)

    Reveles, Caroline C; Segri, Neuber J; Botelho, Clovis

    2013-01-01

    to determine the prevalence and to analyze factors associated with hookah use initiation among adolescents. This was a cross-sectional study, in which questionnaires were collected from 495 students attending public and private schools of the urban area of the city of Várzea Grande, in the state of Mato Grosso, Brazil. Data were analyzed through descriptive, bivariate, and multiple Poisson regression analyses. A total of 19.7% students had tried a hookah. The use of hookah was associated with the final period of adolescence [PR=6.54 (2.79, 15.32)]; enrollment in private schools [PR=2.23 (1.73, 2.88)]; and presence of work activities [PR=1.80 (1.17, 2.78)]. The proportion of adolescents that had tried a hookah was high. The influence of age, work activities, and class period on smoking initiation using the hookah was observed. Preventive measures encompassing all forms of tobacco smoking should be targeted at adolescents in the school environment, aiming at tobacco use control. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  19. The regulation of protein synthesis and translation factors by CD3 and CD28 in human primary T lymphocytes

    Directory of Open Access Journals (Sweden)

    Proud Christopher G

    2002-05-01

    Full Text Available Abstract Background Activation of human resting T lymphocytes results in an immediate increase in protein synthesis. The increase in protein synthesis after 16–24 h has been linked to the increased protein levels of translation initiation factors. However, the regulation of protein synthesis during the early onset of T cell activation has not been studied in great detail. We studied the regulation of protein synthesis after 1 h of activation using αCD3 antibody to stimulate the T cell receptor and αCD28 antibody to provide the co-stimulus. Results Activation of the T cells with both antibodies led to a sustained increase in the rate of protein synthesis. The activities and/or phosphorylation states of several translation factors were studied during the first hour of stimulation with αCD3 and αCD28 to explore the mechanism underlying the activation of protein synthesis. The initial increase in protein synthesis was accompanied by activation of the guanine nucleotide exchange factor, eukaryotic initiation factor (eIF 2B, and of p70 S6 kinase and by dephosphorylation of eukaryotic elongation factor (eEF 2. Similar signal transduction pathways, as assessed using signal transduction inhibitors, are involved in the regulation of protein synthesis, eIF2B activity and p70 S6 kinase activity. A new finding was that the p38 MAPK α/β pathway was involved in the regulation of overall protein synthesis in primary T cells. Unexpectedly, no changes were detected in the phosphorylation state of the cap-binding protein eIF4E and the eIF4E-binding protein 4E-BP1, or the formation of the cap-binding complex eIF4F. Conclusions Both eIF2B and p70 S6 kinase play important roles in the regulation of protein synthesis during the early onset of T cell activation.

  20. Leucine-rich diet alters the eukaryotic translation initiation factors expression in skeletal muscle of tumour-bearing rats

    International Nuclear Information System (INIS)

    Ventrucci, Gislaine; Mello, Maria Alice R; Gomes-Marcondes, Maria Cristina C

    2007-01-01

    Cancer-cachexia induces a variety of metabolic disorders on protein turnorver, decreasing protein synthesis and increasing protein degradation. Controversly, insulin, other hormones, and branched-chain amino acids, especially leucine, stimulate protein synthesis and modulate the activity of translation initiation factors involved in protein synthesis. Since the tumour effects are more pronounced when associated with pregnancy, ehancing muscle-wasting proteolysis, in this study, the influence of a leucine-rich diet on the protein synthesis caused by cancer were investigated. Pregnant rats with or without Walker 256 tumour were distributed into six groups. During 20 days of experiment, three groups were fed with a control diet: C – pregnant control, W – tumour-bearing, and P – pair-fed, which received the same amount of food as ingested by the W group; three other groups of pregnant rats were fed a leucine-rich diet: L – pregnant leucine, WL – tumour-bearing, and PL – pair-fed, which received the same amount of food as ingested by the WL group. The gastrocnemius muscle of WL rats showed increased incorporation of leucine in protein compared to W rats; the leucine-rich diet also prevented the decrease in plasma insulin normally seen in W. The expression of translation initiation factors increased when tumour-bearing rats fed leucine-rich diet, with increase of ~35% for eIF2α and eIF5, ~17% for eIF4E and 20% for eIF4G; the expression of protein kinase S6K1 and protein kinase C was also highly enhanced. The results suggest that a leucine-rich diet increased the protein synthesis in skeletal muscle in tumour-bearing rats possibly through the activation of eIF factors and/or the S6kinase pathway

  1. Factors influencing career choice after initial training in surgery.

    LENUS (Irish Health Repository)

    McHugh, Seamus

    2012-02-01

    INTRODUCTION: Irish general surgery faces a recruitment crisis with only 87 of 145 (60%) basic surgical training (BST) places filled in 2009. We assessed basic surgical trainees to identify objective, and potentially modifiable, factors that influence ultimate recruitment into a general surgical career. METHODS: Candidates commencing BST training during a 5-year period between 2004 and 2008 were included in a quantitative study. In addition a total of 2,536 candidates, representing all those who commenced surgical training in Ireland since 1960 were identified through the Royal College of Surgeons in Ireland (RCSI) database and invited to complete an online survey. Statistical analysis was performed using SPSS version 15, with p < 0.05 considered significant. RESULTS: During the 5-year quantitative study period there were 381 BST trainees. Gender was a significant predictor of career choice with women more likely to ultimately choose a nonsurgical career after initial surgical training (p = 0.049). Passing surgical membership examinations (MRCS) also was predictive of remaining in surgery (p = 0.005). Training region was not a significant predictor of ultimate career choice. There were 418 survey respondents. The influence of role models was most commonly cited as influencing candidates in choosing to commence surgical training. Candidates who rated "academic opportunity" (p = 0.023) and "intellectual challenge" (p = 0.047) as factors that influenced their decision to commence surgical training were more likely to ultimately continue their careers in a surgical speciality. CONCLUSIONS: This study describes the career pathway of surgical trainees and confirms the importance of academic achievement in discriminating between candidates applying for surgical training schemes.

  2. Factors That Drive RTO Performance: An Overview. Synthesis Report

    Science.gov (United States)

    Misko, Josie

    2017-01-01

    This paper provides an overview of recent research on the factors that drive the performance of registered training organisations (RTOs), with a view to identifying areas for future research. Initially it explores the drivers of RTO performance; then discusses findings from available literature from Australia and from overseas, and discusses some…

  3. Factors associated with the lack of antiretroviral therapy initiation ...

    African Journals Online (AJOL)

    Logistic regression models were used to calculate univariate and adjusted multivariate measures of association between ART initiation and the independent variables. Results. Among the 163 pregnant women who were eligible for ART, 110 (67.5%) were initiated on ART by the time of delivery. The most commonly cited ...

  4. HSV usurps eukaryotic initiation factor 3 subunit M for viral protein translation: novel prevention target.

    Directory of Open Access Journals (Sweden)

    Natalia Cheshenko

    2010-07-01

    Full Text Available Prevention of genital herpes is a global health priority. B5, a recently identified ubiquitous human protein, was proposed as a candidate HSV entry receptor. The current studies explored its role in HSV infection. Viral plaque formation was reduced by approximately 90% in human cells transfected with small interfering RNA targeting B5 or nectin-1, an established entry receptor. However, the mechanisms were distinct. Silencing of nectin-1 prevented intracellular delivery of viral capsids, nuclear transport of a viral tegument protein, and release of calcium stores required for entry. In contrast, B5 silencing had no effect on these markers of entry, but inhibited viral protein translation. Specifically, viral immediate early genes, ICP0 and ICP4, were transcribed, polyadenylated and transported from the nucleus to the cytoplasm, but the viral transcripts did not associate with ribosomes or polysomes in B5-silenced cells. In contrast, immediate early gene viral transcripts were detected in polysome fractions isolated from control cells. These findings are consistent with sequencing studies demonstrating that B5 is eukaryotic initiation factor 3 subunit m (eIF3m. Although B5 silencing altered the polysome profile of cells, silencing had little effect on cellular RNA or protein expression and was not cytotoxic, suggesting that this subunit is not essential for host cellular protein synthesis. Together these results demonstrate that B5 plays a major role in the initiation of HSV protein translation and could provide a novel target for strategies to prevent primary and recurrent herpetic disease.

  5. Formation of solar system analogues - I. Looking for initial conditions through a population synthesis analysis

    Science.gov (United States)

    Ronco, M. P.; Guilera, O. M.; de Elía, G. C.

    2017-11-01

    Population synthesis models of planetary systems developed during the last ˜15 yr could reproduce several of the observables of the exoplanet population, and also allowed us to constrain planetary formation models. We present our planet formation model, which calculates the evolution of a planetary system during the gaseous phase. The code incorporates relevant physical phenomena for the formation of a planetary system, like photoevaporation, planet migration, gas accretion, water delivery in embryos and planetesimals, a detailed study of the orbital evolution of the planetesimal population, and the treatment of the fusion between embryos, considering their atmospheres. The main goal of this work, unlike other works of planetary population synthesis, is to find suitable scenarios and physical parameters of the disc to form Solar system analogues. We are specially interested in the final planet distributions, and in the final surface density, eccentricity and inclination profiles for the planetesimal population. These final distributions will be used as initial conditions for N-body simulations to study the post-oligarchic formation in a second work. We then consider different formation scenarios, with different planetesimal sizes and different type I migration rates. We find that Solar system analogues are favoured in massive discs, with low type I migration rates, and small planetesimal sizes. Besides, those rocky planets within their habitables zones are dry when discs dissipate. At last, the final configurations of Solar system analogues include information about the mass and semimajor axis of the planets, water contents, and the properties of the planetesimal remnants.

  6. Translation initiation requires cell division cycle 123 (Cdc123) to facilitate biogenesis of the eukaryotic initiation factor 2 (eIF2).

    Science.gov (United States)

    Perzlmaier, Angelika F; Richter, Frank; Seufert, Wolfgang

    2013-07-26

    The eukaryotic translation initiation factor 2 (eIF2) is central to the onset of protein synthesis and its modulation in response to physiological demands. eIF2, a heterotrimeric G-protein, is activated by guanine nucleotide exchange to deliver the initiator methionyl-tRNA to the ribosome. Here we report that assembly of the eIF2 complex in vivo depends on Cdc123, a cell proliferation protein conserved among eukaryotes. Mutations of CDC123 in budding yeast reduced the association of eIF2 subunits, diminished polysome levels, and increased GCN4 expression indicating that Cdc123 is critical for eIF2 activity. Cdc123 bound the unassembled eIF2γ subunit, but not the eIF2 complex, and the C-terminal domain III region of eIF2γ was both necessary and sufficient for Cdc123 binding. Alterations of the binding site revealed a strict correlation between Cdc123 binding, the biological function of eIF2γ, and its ability to assemble with eIF2α and eIF2β. Interestingly, high levels of Cdc123 neutralized the assembly defect and restored the biological function of an eIF2γ mutant. Moreover, the combined overexpression of eIF2 subunits rescued an otherwise inviable cdc123 deletion mutant. Thus, Cdc123 is a specific eIF2 assembly factor indispensable for the onset of protein synthesis. Human Cdc123 is encoded by a disease risk locus, and, therefore, eIF2 biogenesis control by Cdc123 may prove relevant for normal cell physiology and human health. This work identifies a novel step in the eukaryotic translation initiation pathway and assigns a biochemical function to a protein that is essential for growth and viability of eukaryotic cells.

  7. Early smoking initiation and associated factors among in-school ...

    African Journals Online (AJOL)

    Objective: This report examines the prevalence and common correlates of early smoking initiation among male and female school children across seven African countries. Method: The total sample included 17,725 school children aged 13 to 15 years from nationally representative samples in seven African countries.

  8. An Initial Investigation of Factors Affecting Multi-Task Performance

    National Research Council Canada - National Science Library

    Branscome, Tersa A; Swoboda, Jennifer C; Fatkin, Linda T

    2007-01-01

    This report presents the results of the first in a series of investigations designed to increase fundamental knowledge and understanding of the factors affecting multi-task performance in a military environment...

  9. Sox2 is translationally activated by eukaryotic initiation factor 4E in human glioma-initiating cells

    International Nuclear Information System (INIS)

    Ge, Yuqing; Zhou, Fengbiao; Chen, Hong; Cui, Chunhong; Liu, Dan; Li, Qiuping; Yang, Zhiyuan; Wu, Guoqiang; Sun, Shuhui; Gu, Jianxin; Wei, Yuanyan; Jiang, Jianhai

    2010-01-01

    Sox2, a master transcription factor, contributes to the generation of induced pluripotent stem cells and plays significant roles in sustaining the self-renewal of neural stem cells and glioma-initiating cells. Understanding the functional differences of Sox2 between glioma-initiating cells and normal neural stem cells would contribute to therapeutic approach for treatment of brain tumors. Here, we first demonstrated that Sox2 could contribute to the self-renewal and proliferation of glioma-initiating cells. The following experiments showed that Sox2 was activated at translational level in a subset of human glioma-initiating cells compared with the normal neural stem cells. Further investigation revealed there was a positive correlation between Sox2 and eukaryotic initiation factor 4E (eIF4E) in glioma tissues. Down-regulation of eIF4E decreased Sox2 protein level without altering its mRNA level in glioma-initiating cells, indicating that Sox2 was activated by eIF4E at translational level. Furthermore, eIF4E was presumed to regulate the expression of Sox2 by its 5' untranslated region (5' UTR) sequence. Our results suggest that the eIF4E-Sox2 axis is a novel mechanism of unregulated self-renewal of glioma-initiating cells, providing a potential therapeutic target for glioma.

  10. Influence of environmental factors on growth and pigment synthesis by purple thiobacteria

    Directory of Open Access Journals (Sweden)

    Y. О. Pavlova

    2007-12-01

    Full Text Available The influence of different environmental factors on growth and pigment biosynthesis by particular strains of purple thiobacteria was investigated. These strains belong to the genus Chromatium, Thiocystis, Thiocapsa and Lamprocystis and were isolated from Yavoriv sulphur mine. Calcium, magnesium, manganese, iron and sodium chloride should be included in the medium for optimal growth of these bacteria. Addition of these elements entails increasing the biomass production and synthesis of carotenoids and bacteriochlorophyll a. Initial concentration of inoculum and electron donor has essential influence on growth of purple thiobacteria. Early in the development of culture, sulphide was oxidized, and then the growth impairment and destruction of cells under exposure of light were observed. For the optimization of bacteria growth the electron donor (sulphide must be added many times during the cultivation process in the concentration, which is not exceed an inhibition dose. The additional bringing of the electron donor in the medium promotes the raise of cells’ biomass. The acetate introduction in the medium has positive influence on the pigments’ biosynthesis. The essential factor of growth and pigments’ biosynthesis is the light intensity. Peak gain of the culture growth was observed under 400 lx. The amplification of light exposure is accompanied by the decrease of growth and content of pigments in cells. Oxygen inhibits the synthesis of pigments in all strains

  11. Timing of initiation of macronuclear DNA synthesis is set during the preceding cell cycle in Paramecium tetraurelia: analysis of the effects of abrupt changes in nutrient level

    Energy Technology Data Exchange (ETDEWEB)

    Ching, A.S.L.; Berger, J.D.

    1986-11-01

    In many eukaryotic organisms, initiation of DNA synthesis is associated with a major control point within the cell cycle and reflects the commitment of the cell to the DNA replication-division portion of the cell cycle. In paramecium, the timing of DNA synthesis initiation is established prior to fission during the preceding cell cycle. DNA synthesis normally starts at 0.25 in the cell cycle. When dividing cells are subjected to abrupt nutrient shift-up by transfer from a chemostat culture to medium with excess food, or shift-down from a well-fed culture to exhausted medium, DNA synthesis initiation in the post-shift cell cycle occurs at 0.25 of the parental cell cycle and not at either 0.25 in the post-shift cell cycle or at 0.25 in the equilibrium cell cycle produced under the post-shift conditions. The long delay prior to initiation of DNA synthesis following nutritional shift-up is not a consequence of continued slow growth because the rate of protein synthesis increases rapidly to the normal level after shift-up. Analysis of the relation between increase in cell mass and initiation of DNA synthesis following nutritional shifts indicates that increase in cell mass, per se, is neither a necessary nor a sufficient condition for initiation of DNA synthesis, in spite of the strong association between accumulation of cell mass and initiation of DNA synthesis in cells growing under steady-state conditions.

  12. Timing of initiation of macronuclear DNA synthesis is set during the preceding cell cycle in Paramecium tetraurelia: analysis of the effects of abrupt changes in nutrient level

    International Nuclear Information System (INIS)

    Ching, A.S.L.; Berger, J.D.

    1986-01-01

    In many eukaryotic organisms, initiation of DNA synthesis is associated with a major control point within the cell cycle and reflects the commitment of the cell to the DNA replication-division portion of the cell cycle. In paramecium, the timing of DNA synthesis initiation is established prior to fission during the preceding cell cycle. DNA synthesis normally starts at 0.25 in the cell cycle. When dividing cells are subjected to abrupt nutrient shift-up by transfer from a chemostat culture to medium with excess food, or shift-down from a well-fed culture to exhausted medium, DNA synthesis initiation in the post-shift cell cycle occurs at 0.25 of the parental cell cycle and not at either 0.25 in the post-shift cell cycle or at 0.25 in the equilibrium cell cycle produced under the post-shift conditions. The long delay prior to initiation of DNA synthesis following nutritional shift-up is not a consequence of continued slow growth because the rate of protein synthesis increases rapidly to the normal level after shift-up. Analysis of the relation between increase in cell mass and initiation of DNA synthesis following nutritional shifts indicates that increase in cell mass, per se, is neither a necessary nor a sufficient condition for initiation of DNA synthesis, in spite of the strong association between accumulation of cell mass and initiation of DNA synthesis in cells growing under steady-state conditions

  13. Factors associated with the lack of antiretroviral therapy initiation ...

    African Journals Online (AJOL)

    positive perception). Scores for harms of ART, stigma and need for ART were reversed so that values closer to 5 indicate less harm and stigma; and greater need for ART. †Mann-Whitney (Wilcoxon rank-sum) test. Table 4. Interpersonal factors.

  14. Factors influencing career choice after initial training in surgery.

    LENUS (Irish Health Repository)

    McHugh, Seamus

    2011-03-01

    Irish general surgery faces a recruitment crisis with only 87 of 145 (60%) basic surgical training (BST) places filled in 2009. We assessed basic surgical trainees to identify objective, and potentially modifiable, factors that influence ultimate recruitment into a general surgical career.

  15. An Investigation of Porous Structure of TiNi-Based SHS-Materials Produced at Different Initial Synthesis Temperatures

    Science.gov (United States)

    Khodorenko, V. N.; Anikeev, S. G.; Kokorev, O. V.; Yasenchuk, Yu. F.; Gunther, V. É.

    2018-02-01

    An investigation of structural characteristics and behavior of TiNi-based pore-permeable materials manufactured by the methods of selfpropagating high-temperature synthesis (SHS) at the initial synthesis temperatures T = 400 and 600°C is performed. It is shown that depending on the temperature regime, the resulting structure and properties of the material can differ. It is found out that the SHS-material produced at the initial synthesis temperature T = 400°C possesses the largest number of micropores in the pore wall surface structure due to a high phase inhomogeneity of the alloy. The regime of structure optimization of the resulting materials is described and the main stages of formation of the pore wall microporous surfaces are revealed. It is demonstrated that after optimization of the surface structure of a TiNi-based fine-pore alloy by its chemical etching, the fraction of micropores measuring in size less than 50 nm increased from 59 to 68%, while the number of pores larger than 1 μm increased twofold from 11 to 22%. In addition, peculiar features of interaction between certain cell cultures with the surface of the SHS-material manufactured at different initial synthesis temperatures are revealed. It is found out that the dynamics of the cell material integration depends on the pore wall surface morphology and dimensions of macropores.

  16. Personality Factors and Nuclear Power Plant Operators: Initial License Success

    Science.gov (United States)

    DeVita-Cochrane, Cynthia

    Commercial nuclear power utilities are under pressure to effectively recruit and retain licensed reactor operators in light of poor candidate training completion rates and recent candidate failures on the Nuclear Regulatory Commission (NRC) license exam. One candidate failure can cost a utility over $400,000, making the successful licensing of new operators a critical path to operational excellence. This study was designed to discover if the NEO-PI-3, a 5-factor measure of personality, could improve selection in nuclear utilities by identifying personality factors that predict license candidate success. Two large U.S. commercial nuclear power corporations provided potential participant contact information and candidate results on the 2014 NRC exam from their nuclear power units nation-wide. License candidates who participated (n = 75) completed the NEO-PI-3 personality test and results were compared to 3 outcomes on the NRC exam: written exam, simulated operating exam, and overall exam result. Significant correlations were found between several personality factors and both written and operating exam outcomes on the NRC exam. Further, a regression analysis indicated that personality factors, particularly Conscientiousness, predicted simulated operating exam scores. The results of this study may be used to support the use of the NEO-PI-3 to improve operator selection as an addition to the current selection protocol. Positive social change implications from this study include support for the use of a personality measure by utilities to improve their return-on-investment in candidates and by individual candidates to avoid career failures. The results of this study may also positively impact the public by supporting the safe and reliable operation of commercial nuclear power utilities in the United States.

  17. Chlorpromazine inhibits tumour necrosis factor synthesis and cytotoxicity in vitro.

    Science.gov (United States)

    Zinetti, M; Galli, G; Demitri, M T; Fantuzzi, G; Minto, M; Ghezzi, P; Alzani, R; Cozzi, E; Fratelli, M

    1995-01-01

    Chlorpromazine (CPZ) has been previously shown to protect against endotoxin [lipopolysaccharide (LPS)] lethality and inhibit the release of tumour necrosis factor in vivo. We investigated at the cellular level whether this was due to direct inhibition of tumour necrosis factor-alpha (TNF-alpha) synthesis, using LPS-stimulated THP-1 human monocytic leukemia cells. We also studied the effect of CPZ on human TNF-alpha action by assessing TNF-alpha cytotoxicity on mouse fibrosarcoma L929 cells. CPZ (1-100 microM) inhibited TNF-alpha production in THP-1 cells in a dose dependent manner by a maximum of 80%. This effect was comparable to that of two well-known inhibitory drugs, dexamethasone and cyclicAMP. Inhibition was also evident at the mRNA level. On the other hand CPZ (10-25 microM) also inhibited TNF-alpha activity: in fact it reduced the cytotoxicity of TNF-alpha on L929 cells (EC50 was increased four times) and could provide protection even as a post-treatment. CPZ inhibited TNF-induced apoptosis in L929 cells, as detected by analysis of nuclear morphology. However, since we showed that apoptosis was very limited, and was not the main mode of cell death in our conditions, this could not explain the overall protection. Since CPZ did not interfere with either the oligomerization state of TNF-alpha or its receptor binding, our data suggest that it reduced cytotoxicity by inhibiting some steps in the TNF-alpha signalling pathways. Images Figure 1 Figure 4 PMID:8550079

  18. Chlorpromazine inhibits tumour necrosis factor synthesis and cytotoxicity in vitro.

    Science.gov (United States)

    Zinetti, M; Galli, G; Demitri, M T; Fantuzzi, G; Minto, M; Ghezzi, P; Alzani, R; Cozzi, E; Fratelli, M

    1995-11-01

    Chlorpromazine (CPZ) has been previously shown to protect against endotoxin [lipopolysaccharide (LPS)] lethality and inhibit the release of tumour necrosis factor in vivo. We investigated at the cellular level whether this was due to direct inhibition of tumour necrosis factor-alpha (TNF-alpha) synthesis, using LPS-stimulated THP-1 human monocytic leukemia cells. We also studied the effect of CPZ on human TNF-alpha action by assessing TNF-alpha cytotoxicity on mouse fibrosarcoma L929 cells. CPZ (1-100 microM) inhibited TNF-alpha production in THP-1 cells in a dose dependent manner by a maximum of 80%. This effect was comparable to that of two well-known inhibitory drugs, dexamethasone and cyclicAMP. Inhibition was also evident at the mRNA level. On the other hand CPZ (10-25 microM) also inhibited TNF-alpha activity: in fact it reduced the cytotoxicity of TNF-alpha on L929 cells (EC50 was increased four times) and could provide protection even as a post-treatment. CPZ inhibited TNF-induced apoptosis in L929 cells, as detected by analysis of nuclear morphology. However, since we showed that apoptosis was very limited, and was not the main mode of cell death in our conditions, this could not explain the overall protection. Since CPZ did not interfere with either the oligomerization state of TNF-alpha or its receptor binding, our data suggest that it reduced cytotoxicity by inhibiting some steps in the TNF-alpha signalling pathways.

  19. Synthesis and biological activity of novel mono-indole and mono-benzofuran inhibitors of bacterial transcription initiation complex formation.

    Science.gov (United States)

    Mielczarek, Marcin; Thomas, Ruth V; Ma, Cong; Kandemir, Hakan; Yang, Xiao; Bhadbhade, Mohan; Black, David StC; Griffith, Renate; Lewis, Peter J; Kumar, Naresh

    2015-04-15

    Our ongoing research focused on targeting transcription initiation in bacteria has resulted in synthesis of several classes of mono-indole and mono-benzofuran inhibitors that targeted the essential protein-protein interaction between RNA polymerase core and σ(70)/σ(A) factors in bacteria. In this study, the reaction of indole-2-, indole-3-, indole-7- and benzofuran-2-glyoxyloyl chlorides with amines and hydrazines afforded a variety of glyoxyloylamides and glyoxyloylhydrazides. Similarly, condensation of 2- and 7-trichloroacetylindoles with amines and hydrazines delivered amides and hydrazides. The novel molecules were found to inhibit the RNA polymerase-σ(70)/σ(A) interaction as measured by ELISA, and also inhibited the growth of both Gram-positive and Gram-negative bacteria in culture. Structure-activity relationship (SAR) studies of the mono-indole and mono-benzofuran inhibitors suggested that the hydrophilic-hydrophobic balance is an important determinant of biological activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Glycosaminoglycan synthesis and shedding induced by growth factors are cell and compound specific.

    Science.gov (United States)

    Suarez, Eloah R; Nohara, Angela S; Mataveli, Fábio D; de Matos, Leandro L; Nader, Helena B; Pinhal, Maria Aparecida S

    2007-02-01

    The interactions between growth factors and sulphated glycosaminoglycans (GAG) have been extensively studied. The aim of this study is to investigate if growth factors would show specificity of action on the synthesis and shedding of sulphated GAG, using two different cell lines: endothelial and smooth muscle cells. The cells were grown in the presence or absence of growth factors: EGF, FGF2, VEGF121, VEGF165. Transfection assays were also performed using recombinant pcDNA3.1, containing VEGF165 cDNA. In order to analyse the different types of GAG the cells were metabolically labelled with [(35)S]-sulphate. At low doses, VEGF121 was the only growth factor able to increase both the synthesis and secretion of heparan sulphate (HS) in endothelial cells. Over expression of VEGF165 stimulated HS synthesis in both cells. The combined results showed that growth factors affect GAG synthesis in a cell specific and dose dependent manner.

  1. Lentivirus-mediated knockdown of eukaryotic translation initiation factor 3 subunit D inhibits proliferation of HCT116 colon cancer cells.

    Science.gov (United States)

    Yu, Xiaojun; Zheng, Bo'an; Chai, Rui

    2014-12-12

    Dysregulation of protein synthesis is emerging as a major contributory factor in cancer development. eIF3D (eukaryotic translation initiation factor 3 subunit D) is one member of the eIF3 (eukaryotic translation initiation factor 3) family, which is essential for initiation of protein synthesis in eukaryotic cells. Acquaintance with eIF3D is little since it has been identified as a dispensable subunit of eIF3 complex. Recently, eIF3D was found to embed somatic mutations in human colorectal cancers, indicating its importance for tumour progression. To further probe into its action in colon cancer, we utilized lentivirus-mediated RNA interference to knock down eIF3D expression in one colon cancer cell line HCT116. Knockdown of eIF3D in HCT116 cells significantly inhibited cell proliferation and colony formation in vitro. Flow cytometry analysis indicated that depletion of eIF3D led to cell-cycle arrest in the G2/M phase, and induced an excess accumulation of HCT116 cells in the sub-G1 phase representing apoptotic cells. Signalling pathways responsible for cell growth and apoptosis have also been found altered after eIF3D silencing, such as AMPKα (AMP-activated protein kinase alpha), Bad, PRAS40 [proline-rich Akt (PKB) substrate of 40 kDa], SAPK (stress-activated protein kinase)/JNK (c-Jun N-terminal kinase), GSK3β and PARP [poly(ADP-ribose) polymerase]. Taken together, these findings suggest that eIF3D might play an important role in colon cancer progression.

  2. Structure of the protein core of translation initiation factor 2 in apo, GTP-bound and GDP-bound forms

    International Nuclear Information System (INIS)

    Simonetti, Angelita; Marzi, Stefano; Fabbretti, Attilio; Hazemann, Isabelle; Jenner, Lasse; Urzhumtsev, Alexandre; Gualerzi, Claudio O.; Klaholz, Bruno P.

    2013-01-01

    The crystal structures of the eubacterial translation initiation factor 2 in apo form and with bound GDP and GTP reveal conformational changes upon nucleotide binding and hydrolysis, notably of the catalytically important histidine in the switch II region. Translation initiation factor 2 (IF2) is involved in the early steps of bacterial protein synthesis. It promotes the stabilization of the initiator tRNA on the 30S initiation complex (IC) and triggers GTP hydrolysis upon ribosomal subunit joining. While the structure of an archaeal homologue (a/eIF5B) is known, there are significant sequence and functional differences in eubacterial IF2, while the trimeric eukaryotic IF2 is completely unrelated. Here, the crystal structure of the apo IF2 protein core from Thermus thermophilus has been determined by MAD phasing and the structures of GTP and GDP complexes were also obtained. The IF2–GTP complex was trapped by soaking with GTP in the cryoprotectant. The structures revealed conformational changes of the protein upon nucleotide binding, in particular in the P-loop region, which extend to the functionally relevant switch II region. The latter carries a catalytically important and conserved histidine residue which is observed in different conformations in the GTP and GDP complexes. Overall, this work provides the first crystal structure of a eubacterial IF2 and suggests that activation of GTP hydrolysis may occur by a conformational repositioning of the histidine residue

  3. Structure of the protein core of translation initiation factor 2 in apo, GTP-bound and GDP-bound forms

    Energy Technology Data Exchange (ETDEWEB)

    Simonetti, Angelita [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Marzi, Stefano [Architecture et Réactivité de l’ARN, UPR 9002 CNRS, IBMC (Institute of Molecular and Cellular Biology), 15 Rue R. Descartes, 67084 Strasbourg, France, Université de Strasbourg, 67000 Strasbourg (France); Fabbretti, Attilio [University of Camerino, 62032 Camerino (Monaco) (Italy); Hazemann, Isabelle; Jenner, Lasse [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale -INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Urzhumtsev, Alexandre [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Université de Lorraine, 54506 Vandoeuvre-lès-Nancy (France); Gualerzi, Claudio O. [University of Camerino, 62032 Camerino (Monaco) (Italy); Klaholz, Bruno P., E-mail: klaholz@igbmc.fr [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France)

    2013-06-01

    The crystal structures of the eubacterial translation initiation factor 2 in apo form and with bound GDP and GTP reveal conformational changes upon nucleotide binding and hydrolysis, notably of the catalytically important histidine in the switch II region. Translation initiation factor 2 (IF2) is involved in the early steps of bacterial protein synthesis. It promotes the stabilization of the initiator tRNA on the 30S initiation complex (IC) and triggers GTP hydrolysis upon ribosomal subunit joining. While the structure of an archaeal homologue (a/eIF5B) is known, there are significant sequence and functional differences in eubacterial IF2, while the trimeric eukaryotic IF2 is completely unrelated. Here, the crystal structure of the apo IF2 protein core from Thermus thermophilus has been determined by MAD phasing and the structures of GTP and GDP complexes were also obtained. The IF2–GTP complex was trapped by soaking with GTP in the cryoprotectant. The structures revealed conformational changes of the protein upon nucleotide binding, in particular in the P-loop region, which extend to the functionally relevant switch II region. The latter carries a catalytically important and conserved histidine residue which is observed in different conformations in the GTP and GDP complexes. Overall, this work provides the first crystal structure of a eubacterial IF2 and suggests that activation of GTP hydrolysis may occur by a conformational repositioning of the histidine residue.

  4. Influencing Factors of the Initiation Point in the Parachute-Bomb Dynamic Detonation System

    Science.gov (United States)

    Qizhong, Li; Ye, Wang; Zhongqi, Wang; Chunhua, Bai

    2017-12-01

    The parachute system has been widely applied in modern armament design, especially for the fuel-air explosives. Because detonation of fuel-air explosives occurs during flight, it is necessary to investigate the influences of the initiation point to ensure successful dynamic detonation. In fact, the initiating position exist the falling area in the fuels, due to the error of influencing factors. In this paper, the major influencing factors of initiation point were explored with airdrop and the regularity between initiation point area and factors were obtained. Based on the regularity, the volume equation of initiation point area was established to predict the range of initiation point in the fuel. The analysis results showed that the initiation point appeared area, scattered on account of the error of attitude angle, secondary initiation charge velocity, and delay time. The attitude angle was the major influencing factors on a horizontal axis. On the contrary, secondary initiation charge velocity and delay time were the major influencing factors on a horizontal axis. Overall, the geometries of initiation point area were sector coupled with the errors of the attitude angle, secondary initiation charge velocity, and delay time.

  5. Risk factors associated with injection initiation among drug users in Northern Thailand

    Directory of Open Access Journals (Sweden)

    Suriyanon Vinai

    2006-03-01

    Full Text Available Abstract Background Circumstances surrounding injection initiation have not been well addressed in many developing country contexts. This study aimed to identify demographic factors, sexual behaviors and drug use characteristics related to injection initiation among drug users in northern Thailand. Methods A cross-sectional survey was conducted among 2,231 drug users admitted to the Northern Drug Treatment Center in Mae Rim, Chiang Mai, Thailand, between February 1, 1999 and December 31, 2000. A multiple logistic regression was employed to identify the independent effects from potential risk factors of transition into injection. Results After controlling for other covariates, being 20 years of age or older, single, ever receiving education, urban residence, and having a history of smoking or incarceration were significantly associated with higher likelihood of injection initiation. Multiple sex partners and an experience of sex abuse were associated with an increased risk of injection initiation. Comparing to those whose first drug was opium, individuals using heroin as their initiation drug had greater risk of injection initiation; conversely, those taking amphetamine as their first drug had less risk of injection initiation. Age of drug initiation was negatively associated with the risk of injection initiation: the older the age of drug initiation, the less the risk of injection initiation. Conclusion Injection initiation was related to several demographic factors, sexual behaviors and drug use characteristics. Understanding these factors will benefit the design of approaches to successfully prevent or delay transition into injection.

  6. ERK-dependent phosphorylation of the transcription initiation factor TIF-IA is required for RNA polymerase I transcription and cell growth

    DEFF Research Database (Denmark)

    Zhao, Jian; Yuan, Xuejun; Frödin, Morten

    2003-01-01

    Phosphorylation of transcription factors by mitogen-activated protein kinase (MAPK) cascades links cell signaling with the control of gene expression. Here we show that growth factors induce rRNA synthesis by activating MAPK-dependent signaling cascades that target the RNA polymerase I......-specific transcription initiation factor TIF-IA. Activation of TIF-IA and ribosomal gene transcription is sensitive to PD98059, indicating that TIF-IA is targeted by MAPK in vivo. Phosphopeptide mapping and mutational analysis reveals two serine residues (S633 and S649) that are phosphorylated by ERK and RSK kinases....... Replacement of S649 by alanine inactivates TIF-IA, inhibits pre-rRNA synthesis, and retards cell growth. The results provide a link between growth factor signaling, ribosome production, and cell growth, and may have a major impact on the mechanism of cell transformation....

  7. Initiation, extension, and termination of RNA synthesis by a paramyxovirus polymerase.

    Science.gov (United States)

    Jordan, Paul C; Liu, Cheng; Raynaud, Pauline; Lo, Michael K; Spiropoulou, Christina F; Symons, Julian A; Beigelman, Leo; Deval, Jerome

    2018-02-01

    Paramyxoviruses represent a family of RNA viruses causing significant human diseases. These include measles virus, the most infectious virus ever reported, in addition to parainfluenza virus, and other emerging viruses. Paramyxoviruses likely share common replication machinery but their mechanisms of RNA biosynthesis activities and details of their complex polymerase structures are unknown. Mechanistic and functional details of a paramyxovirus polymerase would have sweeping implications for understanding RNA virus replication and for the development of new antiviral medicines. To study paramyxovirus polymerase structure and function, we expressed an active recombinant Nipah virus (NiV) polymerase complex assembled from the multifunctional NiV L protein bound to its phosphoprotein cofactor. NiV is an emerging highly pathogenic virus that causes severe encephalitis and has been declared a global public health concern due to its high mortality rate. Using negative-stain electron microscopy, we demonstrated NiV polymerase forms ring-like particles resembling related RNA polymerases. We identified conserved sequence elements driving recognition of the 3'-terminal genomic promoter by NiV polymerase, and leading to initiation of RNA synthesis, primer extension, and transition to elongation mode. Polyadenylation resulting from NiV polymerase stuttering provides a mechanistic basis for transcription termination. It also suggests a divergent adaptation in promoter recognition between pneumo- and paramyxoviruses. The lack of available antiviral therapy for NiV prompted us to identify the triphosphate forms of R1479 and GS-5734, two clinically relevant nucleotide analogs, as substrates and inhibitors of NiV polymerase activity by delayed chain termination. Overall, these findings provide low-resolution structural details and the mechanism of an RNA polymerase from a previously uncharacterized virus family. This work illustrates important functional differences yet remarkable

  8. Initiation, extension, and termination of RNA synthesis by a paramyxovirus polymerase

    Science.gov (United States)

    Liu, Cheng; Raynaud, Pauline; Lo, Michael K.; Symons, Julian A.; Beigelman, Leo

    2018-01-01

    Paramyxoviruses represent a family of RNA viruses causing significant human diseases. These include measles virus, the most infectious virus ever reported, in addition to parainfluenza virus, and other emerging viruses. Paramyxoviruses likely share common replication machinery but their mechanisms of RNA biosynthesis activities and details of their complex polymerase structures are unknown. Mechanistic and functional details of a paramyxovirus polymerase would have sweeping implications for understanding RNA virus replication and for the development of new antiviral medicines. To study paramyxovirus polymerase structure and function, we expressed an active recombinant Nipah virus (NiV) polymerase complex assembled from the multifunctional NiV L protein bound to its phosphoprotein cofactor. NiV is an emerging highly pathogenic virus that causes severe encephalitis and has been declared a global public health concern due to its high mortality rate. Using negative-stain electron microscopy, we demonstrated NiV polymerase forms ring-like particles resembling related RNA polymerases. We identified conserved sequence elements driving recognition of the 3′-terminal genomic promoter by NiV polymerase, and leading to initiation of RNA synthesis, primer extension, and transition to elongation mode. Polyadenylation resulting from NiV polymerase stuttering provides a mechanistic basis for transcription termination. It also suggests a divergent adaptation in promoter recognition between pneumo- and paramyxoviruses. The lack of available antiviral therapy for NiV prompted us to identify the triphosphate forms of R1479 and GS-5734, two clinically relevant nucleotide analogs, as substrates and inhibitors of NiV polymerase activity by delayed chain termination. Overall, these findings provide low-resolution structural details and the mechanism of an RNA polymerase from a previously uncharacterized virus family. This work illustrates important functional differences yet remarkable

  9. Initial solidification phenomena: Factors affecting heat transfer in strip casting

    Science.gov (United States)

    Nolli, Paolo

    In the last few years a few companies have announced the final stage of the commercial development of strip casting of steels. In strip casting heat extraction and productivity are limited by the thermal resistance at the interface between processed material and moving mold (rolls for twin-roll strip casters). Among many factors influencing interfacial heat transfer, films of various composition, either formed during casting or deposited before casting on the surface of the rolls, melt superheat and gas atmosphere composition can have a significantly positive or negative effect on the achieved heat transfer rate. From an industrial point view, methods to improve interfacial heat transfer rates must be found, in order to increase productivity. The objective of this research project is to assess if it is feasible to improve heat transfer rates during solidification of steel in direct contact with a copper mold: (1) by the application of thin coatings on the mold surface; (2) by adding a reactive gas species containing sulfur in the gas shrouding where casting is performed. To address the former, solidification experiments were performed with the mold surface either kept uncoated or coated with coatings of different compositions. To address the latter, the experiments were performed in gas shrouding atmospheres with or without sulphydric acid. It was observed that the resulting heat extraction rates were improved by the application of certain coatings and by the addition of H2S to the gas atmosphere. These findings prove that the application of coatings and the use of small amounts of reactive gaseous species containing sulfur may be methods to increase productivity in strip casting. The effect of superheat and the effect of naturally deposited oxides (Mn-oxide) were also evaluated experimentally. A numerical study of the effect of the critical undercooling on the productivity of a twin-roll strip caster showed that the maximum allowable casting speed can be increased

  10. Success factors for strategic change initiatives: a qualitative study of healthcare administrators' perspectives.

    Science.gov (United States)

    Kash, Bita Arbab; Spaulding, Aaron; Johnson, Christopher E; Gamm, Larry

    2014-01-01

    Success factors related to the implementation of change initiatives are well documented and discussed in the management literature, but they are seldom studied in healthcare organizations engaged in multiple strategic change initiatives. The purpose of this study was to identify key success factors related to implementation of change initiatives based on rich qualitative data gathered from health leader interviews at two large health systems implementing multiple change initiatives. In-depth personal interviews with 61 healthcare leaders in the two large systems were conducted and inductive qualitative analysis was employed to identify success factors associated with 13 change initiatives. Results from this analysis were compared to success factors identified in the literature, and generalizations were drawn that add significantly to the management literature, especially to that in the healthcare sector. Ten specific success factors were identified for the implementation of change initiatives. The top three success factors were (1) culture and values, (2) business processes, and (3) people and engagement. Two of the identified success factors are unique to the healthcare sector and not found in the literature on change models: service quality and client satisfaction (ranked fourth of 10) and access to information (ranked ninth). Results demonstrate the importance of human resource functions, alignment of culture and values with change, and business processes that facilitate effective communication and access to information to achieve many change initiatives. The responses also suggest opportunities for leaders of healthcare organizations to more formally recognize the degree to which various change initiatives are dependent on one another.

  11. Minimizing E-factor in the continuous-flow synthesis of diazepam and atropine.

    Science.gov (United States)

    Bédard, Anne-Catherine; Longstreet, Ashley R; Britton, Joshua; Wang, Yuran; Moriguchi, Hideki; Hicklin, Robert W; Green, William H; Jamison, Timothy F

    2017-12-01

    Minimizing the waste stream associated with the synthesis of active pharmaceutical ingredients (APIs) and commodity chemicals is of high interest within the chemical industry from an economic and environmental perspective. In exploring solutions to this area, we herein report a highly optimized and environmentally conscious continuous-flow synthesis of two APIs identified as essential medicines by the World Health Organization, namely diazepam and atropine. Notably, these approaches significantly reduced the E-factor of previously published routes through the combination of continuous-flow chemistry techniques, computational calculations and solvent minimization. The E-factor associated with the synthesis of atropine was reduced by 94-fold (about two orders of magnitude), from 2245 to 24, while the E-factor for the synthesis of diazepam was reduced by 4-fold, from 36 to 9. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Endogenous adenosine curtails lipopolysaccharide-stimulated tumour necrosis factor synthesis

    NARCIS (Netherlands)

    Eigler, A; Greten, T F; Sinha, B; Haslberger, C; Sullivan, G W; Endres, S

    Recent studies have demonstrated the inhibitory effect of exogenous adenosine on TNF production. During inflammation endogenous adenosine levels are elevated and may be one of several anti-inflammatory mediators that reduce TNF synthesis. In the present study the authors investigated this role of

  13. Nuclear transport factor directs localization of protein synthesis during mitosis

    NARCIS (Netherlands)

    Bogaart, Geert van den; Meinema, Anne C.; Krasnikov, Viktor; Veenhoff, Liesbeth M.; Poolman, Bert

    Export of messenger RNA from the transcription site in the nucleus and mRNA targeting to the translation site in the cytoplasm are key regulatory processes in protein synthesis. In yeast, the mRNA-binding proteins Nab2p and Nab4p/Hrp1p accompany transcripts to their translation site, where the

  14. Synthesis of Novel Hydrocarbon Soluble Multifunctional Anionic Initiators: Tools for Synthesis of Novel Dendrimer and Molecular Brush Polymer Architectures

    Science.gov (United States)

    2015-02-09

    DYNACOP Final Conference on Dynamics of Architecturally Complex Polymers: Current and Future Trends, Leeds , England, December 12-14, 2012...high vacuum techniques and butyllithium purged, all glass sealed reactors in the initial work with such an initiator to insure that there are no...to the reactor containing 300 mL of benzene by fracturing the break- seals which resulted in the immediate development of a yellow color

  15. Hepatitis C virus internal ribosome entry site initiates protein synthesis at the authentic initiation codon in yeast

    Czech Academy of Sciences Publication Activity Database

    Mašek, T.; Vopálenský, V.; Horváth, Ondřej; Vortelová, L.; Feketová, Z.; Pospíšek, M.

    2007-01-01

    Roč. 88, č. 7 (2007), s. 1992-2002 ISSN 0022-1317 Grant - others:Grantová agentura UK(CZ) 251/2004/B-BIO/PrF; GA ČR(CZ) GA204/03/1487; GA ČR(CZ) GA301/07/0607 Institutional research plan: CEZ:AV0Z50520514 Keywords : IRES * hepatitida C * kvasinky Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.120, year: 2007

  16. Polyhomologation based on in situ generated Boron-thexyl-silaboracyclic initiating sites: a novel strategy towards the synthesis of polyethylene-based complex architectures

    KAUST Repository

    Zhang, Zhen

    2015-04-10

    A novel strategy, based on the in situ generated Boron-thexyl-silaboracyclic initiating sites for the polyhomologation of dimethylsulfoxonium methylide, has been developed for the synthesis of complex polyethylene-based architectures. As examples, the synthesis of a 4-arm polyethylene star, three (polystyrene)(polyethylene)2 3-miktoarm stars and a PE-branched double graft copolymers are given.

  17. Inhibition of DNA synthesis by chemical carcinogens in cultures of initiated and normal proliferating rat hepatocytes

    International Nuclear Information System (INIS)

    Novicki, D.L.; Rosenberg, M.R.; Michalopoulos, G.

    1985-01-01

    Rat hepatocytes in primary culture can be stimulated to replicate under the influence of rat serum and sparse plating conditions. Higher replication rates are induced by serum from two-thirds partially hepatectomized rats. The effects of carcinogens and noncarcinogens on the ability of hepatocytes to synthesize DNA were examined by measuring the incorporation of [3H]thymidine by liquid scintillation counting and autoradiography. Hepatocyte DNA synthesis was not decreased by ethanol or dimethyl sulfoxide at concentrations less than 0.5%. No effect was observed when 0.1 mM ketamine, Nembutal, hypoxanthine, sucrose, ascorbic acid, or benzo(e)pyrene was added to cultures of replicating hepatocytes. Estrogen, testosterone, tryptophan, and vitamin E inhibited DNA synthesis by approximately 50% at 0.1 mM, a concentration at which toxicity was noticeable. Several carcinogens requiring metabolic activation as well as the direct-acting carcinogen N-methyl-N'-nitro-N-nitrosoguanidine interfered with DNA synthesis. Aflatoxin B1 inhibited DNA synthesis by 50% (ID50) at concentrations between 1 X 10(-8) and 1 X 10(-7) M. The ID50 for 2-acetylaminofluorene was between 1 X 10(-7) and 1 X 10(-6) M. Benzo(a)pyrene and 3'-methyl-4-dimethylaminoazobenzene inhibited DNA synthesis 50% between 1 X 10(-5) and 1 X 10(-4) M. Diethylnitrosamine and dimethylnitrosamine (ID50 between 1 X 10(-4) and 5 X 10(-4) M) and 1- and 2-naphthylamine (ID50 between 1 X 10(-5) and 5 X 10(-4) M) caused inhibition of DNA synthesis at concentrations which overlapped with concentrations that caused measurable toxicity

  18. Electronic factors in catalysis: the volcano curve and the effect of promotion in catalytic ammonia synthesis

    DEFF Research Database (Denmark)

    Dahl, Søren; Logadottir, Ashildur; Jacobsen, C.J.H.

    2001-01-01

    to calculate how these two factors affect the energies of the intermediates and transition states in the ammonia synthesis reaction. We show that a linear relationship exists between the activation energy for N-2 dissociation and the binding energy of adsorbed nitrogen. The ammonia synthesis activity under...... promoted transition metals. We conclude that promotion is most effective for the best non-promoted catalysts and that promotion will always be essential for obtaining an optimal ammonia synthesis catalyst. Analysis of the micro-kinetic model show that the best catalysts are those with the lowest apparent...

  19. A Network of AOPs for reduced thyroid hormone synthesis derived from inhibition of Thyroperoxidase - A common Molecular Initiating Event Leading to Species-Specific Indices of Adversity.

    Science.gov (United States)

    This collection of 3 AOPs describe varying outcomes of adversity dependent upon species in response to inhibition of thyroperoxidase (TPO) during development. Chemical inhibition of TPO, the molecular-initiating event (MIE), results in decreased thyroid hormone (TH) synthesis, a...

  20. Mixed messages: Re-initiation factors regulate translation of animal mRNAs

    OpenAIRE

    Obermayer, Benedikt; Rajewsky, Nikolaus

    2014-01-01

    When ribosomes encounter upstream open reading frames (uORFs) during scanning of the 5' untranslated region (5' UTR), translation of the downstream ORF requires re-initiation. In a recent paper in Nature, Schleich et al. describe metazoan factors which specifically promote re-initiation.

  1. Histamine suppresses gene expression and synthesis of tumor necrosis factor alpha via histamine H2 receptors

    OpenAIRE

    1991-01-01

    Histamine and tumor necrosis factor alpha (TNF-alpha) can each contribute to the pathogenesis of allergic reactions and chronic inflammatory diseases. We now report the effect of histamine on gene expression and total cellular synthesis of TNF-alpha. Lipopolysaccharide (LPS)-induced synthesis of TNF-alpha in peripheral blood mononuclear cells (PBMC) from 18 healthy donors was suppressed by histamine concentrations from 10(-6) to 10(-4) M, levels comparable with those measured in tissues after...

  2. Measurement of Blood Coagulation Factor Synthesis in Cultures of Human Hepatocytes.

    Science.gov (United States)

    Heinz, Stefan; Braspenning, Joris

    2015-01-01

    An important function of the liver is the synthesis and secretion of blood coagulation factors. Within the liver, hepatocytes are involved in the synthesis of most blood coagulation factors, such as fibrinogen, prothrombin, factor V, VII, IX, X, XI, XII, as well as protein C and S, and antithrombin, whereas liver sinusoidal endothelial cells produce factor VIII and von Willebrand factor. Here, we describe methods for the detection and quantification of most blood coagulation factors in hepatocytes in vitro. Hepatocyte cultures indeed provide a valuable tool to study blood coagulation factors. In addition, the generation and expansion of hepatocytes or hepatocyte-like cells may be used in future for cell-based therapies of liver diseases, including blood coagulation factor deficiencies.

  3. Renal protein synthesis in diabetes mellitus: effects of insulin and insulin-like growth factor I

    International Nuclear Information System (INIS)

    Barac-Nieto, M.; Lui, S.M.; Spitzer, A.

    1991-01-01

    Is increased synthesis of proteins responsible for the hypertrophy of kidney cells in diabetes mellitus? Does the lack of insulin, and/or the effect of insulin-like growth factor I (IGFI) on renal tubule protein synthesis play a role in diabetic renal hypertrophy? To answer these questions, we determined the rates of 3H-valine incorporation into tubule proteins and the valine-tRNA specific activity, in the presence or absence of insulin and/or IGFI, in proximal tubule suspension isolated from kidneys of streptozotocin diabetic and control rats. The rate of protein synthesis increased, while the stimulatory effects of insulin and IGFI on tubule protein synthesis were reduced, early (96 hours) after induction of experimental diabetes. Thus, hypertrophy of the kidneys in experimental diabetes mellitus is associated with increases in protein synthesis, rather than with decreases in protein degradation. Factor(s) other than the lack of insulin, or the effects of IGFI, must be responsible for the high rate of protein synthesis present in the hypertrophying tubules of diabetic rats

  4. Factors Associated with the Transition from Drug Abuse to Initiation of Injection Drug Use

    Directory of Open Access Journals (Sweden)

    Mosayeb Yarmohamadi Vasel

    2015-06-01

    Full Text Available Objectives: Drug injection carries with it many risks and therefore it is important to understand the initiating factors of injection and its origins. Thus,  the purpose of this study was to identify factors associated with the initiation of injection drug use among substance abusers. Methods:  Study method was a cross-sectional study. The research statistics universe constitutes all people suffering from a substance dependence disorder with a pattern of injection use in Tehran and Hamedan. This study was conducted among 216 individuals with substance dependence disorders who were selected from harm reduction centers in Tehran and Hamedan. The sampling selection method was simply random. The instruments used for data collection included: demographic information, patterns of drug use and initiation of injection scales.  Results: In this study, the average age of initiation to injections was 22.5 years. Factors associated with initiation of drug injection included: acquired more pleasure, easier use, faster effect of injection, ineffective previous use method, curiosity, peer pressure, lack of availability of the drug, poverty, and low quality drugs. Discussion: Results of this study indicate that initiation factors to drug injection are multifaceted (Psychological, Social, Economic and Environmental, therefore, injection interventionists should consider all these factors for prevention, treatment and harm reduction.

  5. A Contextual Factors Framework to Inform Implementation and Evaluation of Public Health Initiatives

    Science.gov (United States)

    Vanderkruik, Rachel; McPherson, Marianne E.

    2017-01-01

    Evaluating initiatives implemented across multiple settings can elucidate how various contextual factors may influence both implementation and outcomes. Understanding context is especially critical when the same program has varying levels of success across settings. We present a framework for evaluating contextual factors affecting an initiative…

  6. Socio-Cultural Factors Associated with the Initiation of Opium Use in Darab, Iran

    Science.gov (United States)

    Jafari, Siavash; Movaghar, Afarin Rahimi; Craib, Kevin; Baharlou, Souzan; Mathias, Richard

    2009-01-01

    This study aimed to identify socio-cultural factors facilitating initiation of opium use among drug users in Darab, Iran. A qualitative study using in-depth interviews was conducted. The study began in June 2006 and included 76 drug users, aged 20-43, of whom 95% (72) were male, and 5% (4) were female. The five most common factors facilitating…

  7. Gender differences in risk factors for cigarette smoking initiation in childhood.

    Science.gov (United States)

    Sylvestre, Marie-Pierre; Wellman, Robert J; O'Loughlin, Erin K; Dugas, Erika N; O'Loughlin, Jennifer

    2017-09-01

    We investigated whether established risk factors for initiating cigarette smoking during adolescence (parents, siblings, friends smoke; home smoking rules, smokers at home, exposure to smoking in cars, academic performance, susceptibility to smoking, depressive symptoms, self-esteem, school connectedness, use of other tobacco products) are associated with initiation in preadolescents, and whether the effects of these factors differ by gender. In spring 2005, baseline data were collected in self-report questionnaires from 1801 5th grade students including 1553 never-smokers (mean age=10.7years), in the longitudinal AdoQuest I Study in Montréal, Canada. Follow-up data were collected in the fall and spring of 6th grade (2005-2006). Poisson regression analyses with robust variance estimated the effects of each risk factor on initiation and additive interactions with gender were computed to assess the excess risk of each risk factor in girls compared to boys. 101 of 1399 participants in the analytic sample (6.7% of boys; 7.7% of girls) initiated smoking during follow-up. After adjustment for age, gender and maternal education, all risk factors except academic performance and school connectedness were statistically significantly associated with initiation. Paternal and sibling smoking were associated with initiation in girls only, and girls with lower self-esteem had a significant excess risk of initiating smoking in 6th grade. Risk factors for smoking initiation in preadolescents mirror those in adolescents; their effects do not differ markedly by gender. Preventive programs targeting children should focus on reducing smoking in the social environment and the dangers of poly-tobacco use. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. An investigation of factors predicting the type of bladder antimuscarinics initiated in Medicare nursing homes residents.

    Science.gov (United States)

    Moga, Daniela C; Wu, Qishan; Doshi, Pratik; Goodin, Amie J

    2017-12-28

    To examine factors predicting type of bladder antimuscarinics (BAM) initiated in nursing home (NH) residents. Incident BAM initiators following NH admission were identified by constructing a retrospective cohort from Medicare files and Minimum Data Set (MDS). Participants included all residents 65 years and older admitted in Medicare-certified NH between January 1, 2007 and December 31, 2008 who were prescribed BAM and had continuous Medicare (Part A, B, and D) enrollment. Patient characteristics, medications, and comorbidities were derived from Medicare enrollment and claims. NH characteristics and health status were derived from MDS assessments. The outcome was defined as type of BAM initiated after admission (selective, non-selective extended release, non-selective immediate release). Multinomial logistic regression using generalized estimating equation methodology determined which factors predicted the type of BAM initiated. Twelve thousand eight hundred ninety-nine NH residents initiating BAM therapy were identified; 13.38% of new users were prescribed selective BAM, 45.56% non-selective extended release, and 41.07% non-selective immediate release medications. In both sexes, significant predictors of BAM included region of nursing home, body mass index, cognitive performance score, frailty measures, activities of daily living, and measures of bladder continence. In women, history of fracture and fall-related injuries were significant predictors of type of BAM use, while race and indicators of balance were significant predictors of type of BAM use in men. Non-pharmacological continence management strategies were not predictive of type of BAM initiation. Several factors are important in predicting type of BAM initiation in both women and men, but other factors are sex-specific. Some observed factors predicting the type of BAM initiated, such as other medications use, body mass index, or provider-related factors are potentially modifiable and could be used in

  9. Phosphorylation of Eukaryotic Initiation Factor-2α during Stress and Encystation in Entamoeba Species.

    Science.gov (United States)

    Hendrick, Holland M; Welter, Brenda H; Hapstack, Matthew A; Sykes, Steven E; Sullivan, William J; Temesvari, Lesly A

    2016-12-01

    Entamoeba histolytica is an enteric pathogen responsible for amoebic dysentery and liver abscess. It alternates between the host-restricted trophozoite form and the infective environmentally-stable cyst stage. Throughout its lifecycle E. histolytica experiences stress, in part, from host immune pressure. Conversion to cysts is presumed to be a stress-response. In other systems, stress induces phosphorylation of a serine residue on eukaryotic translation initiation factor-2α (eIF2α). This inhibits eIF2α activity resulting in a general decline in protein synthesis. Genomic data reveal that E. histolytica possesses eIF2α (EheIF2α) with a conserved phosphorylatable serine at position 59 (Ser59). Thus, this pathogen may have the machinery for stress-induced translational control. To test this, we exposed cells to different stress conditions and measured the level of total and phospho-EheIF2α. Long-term serum starvation, long-term heat shock, and oxidative stress induced an increase in the level of phospho-EheIF2α, while short-term serum starvation, short-term heat shock, or glucose deprivation did not. Long-term serum starvation also caused a decrease in polyribosome abundance, which is in accordance with the observation that this condition induces phosphorylation of EheIF2α. We generated transgenic cells that overexpress wildtype EheIF2α, a non-phosphorylatable variant of eIF2α in which Ser59 was mutated to alanine (EheIF2α-S59A), or a phosphomimetic variant of eIF2α in which Ser59 was mutated to aspartic acid (EheIF2α-S59D). Consistent with the known functions of eIF2α, cells expressing wildtype or EheIF2α-S59D exhibited increased or decreased translation, respectively. Surprisingly, cells expressing EheIF2α-S59A also exhibited reduced translation. Cells expressing EheIF2α-S59D were more resistant to long-term serum starvation underscoring the significance of EheIF2α phosphorylation in managing stress. Finally, phospho-eIF2α accumulated during

  10. Factors Associated with Breastfeeding Initiation: A Comparison between France and French-Speaking Canada.

    Directory of Open Access Journals (Sweden)

    Lisa-Christine Girard

    Full Text Available Breastfeeding is associated with multiple domains of health for both mothers and children. Nevertheless, breastfeeding initiation is low within certain developed countries. Furthermore, comparative studies of initiation rates using harmonised data across multiple regions is scarce.The aim of the present study was to investigate and compare individual-level determinants of breastfeeding initiation using two French-speaking cohorts.Participants included ~ 3,900 mothers enrolled in two cohort studies in Canada and France. Interviews, questionnaires, and medical records were utilised to collect information on maternal, family, and medical factors associated with breastfeeding initiation.Rates of breastfeeding initiation were similar across cohorts, slightly above 70%. Women in both Canada and France who had higher levels of maternal education, were born outside of their respective countries and who did not smoke during pregnancy were more likely to initiate breastfeeding with the cohort infant. Notably, cohort effects of maternal education at the university level were found, whereby having 'some university' was not statistically significant for mothers in France. Further, younger mothers in Canada, who delivered by caesarean section and who had previous children, had reduced odds of breastfeeding initiation. These results were not found for mothers in France.While some similar determinants were observed, programming efforts to increase breastfeeding initiation should be tailored to the characteristics of specific geographical regions which may be heavily impacted by the social, cultural and political climate of the region, in addition to individual and family level factors.

  11. Negative effect of the M184V mutation in HIV-1 reverse transcriptase on initiation of viral DNA synthesis

    International Nuclear Information System (INIS)

    Xin Wei; Chen Liang; Goette, Matthias; Wainberg, Mark A.

    2003-01-01

    The M184V mutation in HIV reverse transcriptase (RT) is associated with high-level resistance against the nucleoside inhibitor lamivudine as well as diminished viral replication capacity. We have previously demonstrated that HIV variants containing the M184V mutation were relatively unable to successfully undergo compensatory mutagenesis following deletion of an A-rich loop located upstream of the primer binding site (PBS). To understand the mechanisms involved, we synthesized viral RNA templates containing different compensatory mutations that were emergent during the long-term culture of the A-rich loop-deleted viruses. These templates were then used in cell-free reverse transcription initiation assays and in tRNA primer placement assays performed with either recombinant wild-type RT or recombinant RT containing the M184V substitution. The results showed that the RNA template that contained the A-rich loop deletion was impaired in ability to initiate reverse transcription and that the presence of the M184V substitution in RT amplified this effect. Clearance from pausing at position +3 during synthesis of viral DNA was identified as a sensitive step in this reaction that could not be efficiently bypassed with the M184V mutant enzyme. Increased efficiency of initiation was seen with the deleted RNA templates that also contained mutations identified in the revertant viruses, provided that these mutations facilitated formation of a competent binary tRNA/RNA complex. These findings provide biochemical evidence that initiation of tRNA Lys3 -primed DNA synthesis is an important rate-limiting step in reverse transcription that correlates with viral replication fitness

  12. Keeping Students on Track to Graduate: A Synthesis of School Dropout Trends, Prevention, and Intervention Initiatives

    Science.gov (United States)

    Ecker-Lyster, Meghan; Niileksela, Christopher

    2016-01-01

    This article reviews the literature on dropout trends, prevention, and intervention initiatives for school-aged children. Theoretical and consequential trends are highlighted to offer educators a perspective in which to view the dropout problem. This article also examines current trends in prevention and intervention initiatives aimed at reducing…

  13. The Ecosystem Factor in Supporting Wiki Initiative for Knowledge Sharing in Malaysian Public Organisation

    Directory of Open Access Journals (Sweden)

    Khairil Hizar Md Khuzaimah

    2015-10-01

    Full Text Available The purpose of this paper is to highlight the significance of considering the organizational ecosystem in implementing wikis for knowledge sharing.The findings suggest that a prerequisite of an effective wiki is the appreciation of the factors that make up the organizational ecosystem; technical and organizational factors are variable elements of the ecosystem that can significantly impact the wiki; and the task of re-aligning an existing wiki taking into consideration these factors can be complex.The case study was based on knowledge sharing in a public project management organization, thereby limiting the generalizability to other organizations. Organizations which are keen to adopt wiki as part of their knowledge management initiative need to contextualize their wiki initiative within the organizational context.This research contributes to extending the knowledge-base of the factors that impact the effectiveness of wikis for knowledge sharing by linking the wiki to the broader organizational factors.

  14. Early initiation of breastfeeding: a systematic literature review of factors and barriers in South Asia.

    Science.gov (United States)

    Sharma, Indu K; Byrne, Abbey

    2016-01-01

    Early or timely initiation of breastfeeding is crucial in preventing newborn deaths and influences childhood nutrition however remains low in South Asia and the factors and barriers warrant greater consideration for improved action. This review synthesises the evidence on factors and barriers to initiation of breastfeeding within 1 h of birth in South Asia encompassing Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan and Sri Lanka. Studies published between 1990 and 2013 were systematically reviewed through identification in Academic Search Complete, CINAHL, Global Health, MEDLINE and Scopus databases. Twenty-five studies meeting inclusion criteria were included for review. Structured thematic analysis based on leading frameworks was undertaken to understand factors and barriers. Factors at geographical, socioeconomic, individual, and health-specific levels, such as residence, education, occupation, income, mother's age and newborn's gender, and ill health of mother and newborn at delivery, affect early or timely breastfeeding initiation in South Asia. Reported barriers impact through influence on acceptability by traditional feeding practices, priests' advice, prelacteal feeding and discarding colostrum, mother-in-law's opinion; availability and accessibility through lack of information, low access to media and health services, and misperception, support and milk insufficiency, involvement of mothers in decision making. Whilst some barriers manifest similarly across the region some factors are context-specific thus tailored interventions are imperative. Initiatives halting factors and directed towards contextual barriers are required for greater impact on newborn survival and improved nutrition in the South Asia region.

  15. Characterization of a eukaryotic translation initiation factor 5A homolog from Tamarix androssowii involved in plant abiotic stress tolerance.

    Science.gov (United States)

    Wang, Liuqiang; Xu, Chenxi; Wang, Chao; Wang, Yucheng

    2012-07-26

    The eukaryotic translation initiation factor 5A (eIF5A) promotes formation of the first peptide bond at the onset of protein synthesis. However, the function of eIF5A in plants is not well understood. In this study, we characterized the function of eIF5A (TaeIF5A1) from Tamarix androssowii. The promoter of TaeIF5A1 with 1,486 bp in length was isolated, and the cis-elements in the promoter were identified. A WRKY (TaWRKY) and RAV (TaRAV) protein can specifically bind to a W-box motif in the promoter of TaeIF5A1 and activate the expression of TaeIF5A1. Furthermore, TaeIF5A1, TaWRKY and TaRAV share very similar expression pattern and are all stress-responsive gene that functions in the abscisic acid (ABA) signaling pathway, indicating that they are components of a single regulatory pathway. Transgenic yeast and poplar expressing TaeIF5A1 showed elevated protein levels combined with improved abiotic stresses tolerance. Furthermore, TaeIF5A1-transformed plants exhibited enhanced superoxide dismutase (SOD) and peroxidase (POD) activities, lower electrolyte leakage and higher chlorophyll content under salt stress. These results suggested that TaeIF5A1 is involved in abiotic stress tolerance, and is likely regulated by transcription factors TaWRKY and TaRAV both of which can bind to the W-box motif. In addition, TaeIF5A1 may mediate stress tolerance by increasing protein synthesis, enhancing ROS scavenging by improving SOD and POD activities, and preventing chlorophyll loss and membrane damage. Therefore, eIF5A may play an important role in plant adaptation to changing environmental conditions.

  16. Characterization of a eukaryotic translation initiation factor 5A homolog from Tamarix androssowii involved in plant abiotic stress tolerance

    Directory of Open Access Journals (Sweden)

    Wang Liuqiang

    2012-07-01

    Full Text Available Abstract Background The eukaryotic translation initiation factor 5A (eIF5A promotes formation of the first peptide bond at the onset of protein synthesis. However, the function of eIF5A in plants is not well understood. Results In this study, we characterized the function of eIF5A (TaeIF5A1 from Tamarix androssowii. The promoter of TaeIF5A1 with 1,486 bp in length was isolated, and the cis-elements in the promoter were identified. A WRKY (TaWRKY and RAV (TaRAV protein can specifically bind to a W-box motif in the promoter of TaeIF5A1 and activate the expression of TaeIF5A1. Furthermore, TaeIF5A1, TaWRKY and TaRAV share very similar expression pattern and are all stress-responsive gene that functions in the abscisic acid (ABA signaling pathway, indicating that they are components of a single regulatory pathway. Transgenic yeast and poplar expressing TaeIF5A1 showed elevated protein levels combined with improved abiotic stresses tolerance. Furthermore, TaeIF5A1-transformed plants exhibited enhanced superoxide dismutase (SOD and peroxidase (POD activities, lower electrolyte leakage and higher chlorophyll content under salt stress. Conclusions These results suggested that TaeIF5A1 is involved in abiotic stress tolerance, and is likely regulated by transcription factors TaWRKY and TaRAV both of which can bind to the W-box motif. In addition, TaeIF5A1 may mediate stress tolerance by increasing protein synthesis, enhancing ROS scavenging by improving SOD and POD activities, and preventing chlorophyll loss and membrane damage. Therefore, eIF5A may play an important role in plant adaptation to changing environmental conditions.

  17. Support for food policy initiatives is associated with knowledge of obesity-related cancer risk factors

    Directory of Open Access Journals (Sweden)

    Wendy Watson

    2017-12-01

    Full Text Available Objectives: To investigate community support for government-led policy initiatives to positively influence the food environment, and to identify whether there is a relationship between support for food policy initiatives and awareness of the link between obesity-related lifestyle risk factors and cancer. Methods: An online survey of knowledge of cancer risk factors and attitudes to policy initiatives that influence the food environment was completed by 2474 adults from New South Wales, Australia. The proportion of participants in support of seven food policy initiatives was quantified in relation to awareness of the link between obesity, poor diet, insufficient fruit and vegetable consumption, and physical inactivity with cancer and other health conditions. Results: Overall, policies that involved taxing unhealthy foods received the least support (41.5%. Support was highest for introducing a colour-coded food labelling system (85.9%, restricting claims being made about the health benefits of foods which are, overall, unhealthy (82.6%, displaying health warning labels on unhealthy foods (78.7% and banning unhealthy food advertising that targets children (72.6%. Participants who were aware that obesity-related lifestyle factors are related to cancer were significantly more likely to support food policy initiatives than those who were unaware. Only 17.5% of participants were aware that obesity, poor diet, insufficient fruit and vegetable consumption, and physical inactivity are linked to cancer. Conclusions: There is strong support for all policies related to food labelling and a policy banning unhealthy food advertising to children. Support for food policy initiatives that positively influence the food environment was higher among those who were aware of the link between cancer and obesity-related lifestyle factors than among those who were unaware of this link. Increasing awareness of the link between obesity-related lifestyle factors and cancer

  18. [Risk factors for initial bowel resection and postoperative recurrence in patients with Crohn disease].

    Science.gov (United States)

    Yang, Rong-Ping; Gao, Xiang; Chen, Min-Hu; Xiao, Ying-Lian; Chen, Bai-Li; Hu, Pin-Jin

    2011-03-01

    To investigate the risk factors for the initial bowel resection and postoperative recurrence in a cohort of patients with Crohn disease(CD). A total of 216 consecutive patients who were regularly followed up in the Department of Gastroenterology at the First Affiliated Hospital of Sun Yat-sen University between 2003 and 2009 were included. Probabilities for initial intestinal resection were calculated with Kaplan-Meier method. The influence of concomitant covariates on the cumulative probability rates was examined using Cox proportional hazard model. The risk of postoperative recurrence, including endoscopic recurrence, clinical recurrence and surgical recurrence, was also investigated during the follow-up. Logistic analysis was performed for the risk factors of recurrence. The median follow-up was 55 months. A total of 44 patients(20.4%) underwent bowel resection. The cumulative frequency of surgery was 11%, 25%, and 45% at 1, 5, and 10 years after initial onset. Multivariate analyses showed that age at diagnosis and disease behavior were independent risk factors for initial intestinal resection(Pdisease was the only independent risk factor for clinical recurrence(Pdisease behavior are associated with the probability of initial surgery. The presence of perianal disease is associated with a higher risk of clinical recurrence.

  19. Formylation of initiator tRNA methionine in procaryotic protein synthesis: in vivo polarity in lactose operon expression.

    Science.gov (United States)

    Petersen, H U; Joseph, E; Ullmann, A; Danchin, A

    1978-01-01

    Eucaryotic and procaryotic organisms differ in two aspects of their translation machinery: polycistronic messengers are expressed as a sequence of individual proteins only in procaryotes, and the initiation of protein synthesis proceeds with an initiator tRNA which is found to be modified (formylated) in procaryotes and not in eucaryotes. In the present study, we show that formylation is required in vivo for the coordinate expression of the Escherichia coli lactose operon. Our experiments are consistent with a translation mechanism using dissociated ribosomes at the 5' end of the mRNA in a reaction that is only weakly dependent on formylation at this initiation step; the ribosomes then travel along the messenger and can reinitiate after the intracistronic barrier without dissociation. This latter initiation step is strongly dependent on the level of formylation: a low level of the formyl group, obtained by the antifolic agent trimethoprim, induces a strong polarity in the expression of the lactose operon. There exist mutant strains in which this polarity is much less apparent than in the wild type. We show here that such is the case of rpsL mutants. Ribosomes mutated in the S12 protein (rpsL) are found to be much more easily dissociated than the wild type. This might explain why the expression of the lactose operon on rpsL strains remains coordinated when the intracellular level of formylation is decreased. PMID:98518

  20. The Pennsylvania quality initiative : a synthesis of customer satisfaction and additional research needs

    Science.gov (United States)

    1999-10-29

    Customer satisfaction is at the heart of the Pennsylvania Quality Initiative (PQI), which was created in 1994 to build a more effective partnership among all the stakeholders involved in the process of designing, building, operating, and maintaining ...

  1. Molecular Differentiated Initiator Reactivity in the Synthesis of Poly(caprolactone-Based Hydrophobic Homopolymer and Amphiphilic Core Corona Star Polymers

    Directory of Open Access Journals (Sweden)

    Eileen Deng

    2015-11-01

    Full Text Available Macromolecules that possess three-dimensional, branched molecular structures are of great interest because they exhibit significantly differentiated application performance compared to conventional linear (straight chain polymers. This paper reports the synthesis of 3- and 4-arm star branched polymers via ring opening polymerisation (ROP utilising multi-functional hydroxyl initiators and Sn(Oct2 as precatalyst. The structures produced include mono-functional hydrophobic and multi-functional amphiphilic core corona stars. The characteristics of the synthetic process were shown to be principally dependent upon the physical/dielectric properties of the initiators used. ROP’s using initiators that were more available to become directly involved with the Sn(Oct2 in the “in-situ” formation of the true catalytic species were observed to require shorter reaction times. Use of microwave heating (MWH in homopolymer star synthesis reduced reaction times compared to conventional heating (CH equivalents, this was attributed to an increased rate of “in-situ” catalyst formation. However, in amphiphilic core corona star formation, the MWH polymerisations exhibited slower propagation rates than CH equivalents. This was attributed to macro-structuring within the reaction medium, which reduced the potential for reaction. It was concluded that CH experiments were less affected by this macro-structuring because it was disrupted by the thermal currents/gradients caused by the conductive/convective heating mechanisms. These gradients are much reduced/absent with MWH because it selectively heats specific species simultaneously throughout the entire volume of the reaction medium. These partitioning problems were overcome by introducing additional quantities of the species that had been determined to selectively heat.

  2. Molecular Differentiated Initiator Reactivity in the Synthesis of Poly(caprolactone)-Based Hydrophobic Homopolymer and Amphiphilic Core Corona Star Polymers.

    Science.gov (United States)

    Deng, Eileen; Nguyen, Nam T; Hild, Frédéric; Hamilton, Ian E; Dimitrakis, Georgios; Kingman, Samuel W; Lau, Phei-Li; Irvine, Derek J

    2015-11-09

    Macromolecules that possess three-dimensional, branched molecular structures are of great interest because they exhibit significantly differentiated application performance compared to conventional linear (straight chain) polymers. This paper reports the synthesis of 3- and 4-arm star branched polymers via ring opening polymerisation (ROP) utilising multi-functional hydroxyl initiators and Sn(Oct)2 as precatalyst. The structures produced include mono-functional hydrophobic and multi-functional amphiphilic core corona stars. The characteristics of the synthetic process were shown to be principally dependent upon the physical/dielectric properties of the initiators used. ROP's using initiators that were more available to become directly involved with the Sn(Oct)₂ in the "in-situ" formation of the true catalytic species were observed to require shorter reaction times. Use of microwave heating (MWH) in homopolymer star synthesis reduced reaction times compared to conventional heating (CH) equivalents, this was attributed to an increased rate of "in-situ" catalyst formation. However, in amphiphilic core corona star formation, the MWH polymerisations exhibited slower propagation rates than CH equivalents. This was attributed to macro-structuring within the reaction medium, which reduced the potential for reaction. It was concluded that CH experiments were less affected by this macro-structuring because it was disrupted by the thermal currents/gradients caused by the conductive/convective heating mechanisms. These gradients are much reduced/absent with MWH because it selectively heats specific species simultaneously throughout the entire volume of the reaction medium. These partitioning problems were overcome by introducing additional quantities of the species that had been determined to selectively heat.

  3. Air Force Officer Qualifying Test Form T: Initial Item-, Test-, Factor-, and Composite-Level Analyses

    Science.gov (United States)

    2016-12-01

    Air Force Officer Qualifying Test, Form T1 AFOQT T2 Air Force Officer Qualifying Test, Form T2 AGFI Adjusted Goodness of Fit Index AI Air Force...Qualifying Test Electrical Maze subtest g General mental ability factor GFI Goodness of Fit Index GLS Generalized Least Squares GS Air Force...AFRL-RH-WP-TR-2016-0093 AIR FORCE OFFICER QUALIFYING TEST FORM T: INITIAL ITEM-, TEST-, FACTOR-, AND COMPOSITE-LEVEL ANALYSES

  4. SYNTHESIS OF ARTS AS A FACTOR OF TEENAGE CREATIVE EDUCATION

    Directory of Open Access Journals (Sweden)

    Liudmila Onofrichuk

    2017-03-01

    Full Text Available The article presents the method of teenage creative education by means of musical and theatrical arts at secondary comprehensive school. Showing school musical puppet theater «Fantasy» (secondary school No.12, Vinnytsia the author highlights the ways of pupils’ artistic and creative education during the study of the synthesis of the arts (music, singing, dance and recitation. The conditions affecting successful solution of the problem have been determined. Аmong them the author defines educational activities of a competent teacher who is capable to find out creative innovative solutions. The necessity and importance of using effective methods and techniques in terms of musical and theatrical activities for the development of pupils’ emotional sensitivity and overall creative development have been grounded. During music lessons, pupils successfully master creative abilities and skills (artistic speech, drama, puppet games, dancing, find innovate solutions to practical problems, interpret the original artistic images. Creative combinations of various forms and methods of work, rehearsals, spectacles, concert performances – promote the development of creativity, intensify artistic and performing activities of pupils. The awareness of the character’s motives is the impetus for creating the right stage feeling about reality and naturalness of stage action. It is noted that the art of musical theater helps them not only to acquire art knowledge and skills, but also strive for self-realization and self-improvement, better understanding of themselves and other people, awareness of the beauty of the life. The educational value of the theatrical activity lies in the understanding by teenagers their own attitude to the behavior of characters, developing the abilities to judge them critically, empathize and find alternatives for acquiring creative experience in future life situations.

  5. Social-cognitive and school factors in initiation of smoking among adolescents: a prospective cohort study

    DEFF Research Database (Denmark)

    Bidstrup, Pernille Envold; Frederiksen, Kirsten; Siersma, Volkert

    2009-01-01

    -efficacy, social influence (norms), social influence (behavior), social influence (pressure), and attitude. We used multilevel analyses to estimate the associations between social-cognitive factors at baseline and smoking initiation as well as the random effects of school, school class, and gender group...

  6. Exploring Factors Influencing Collaborative Knowledge Construction in Online Discussions: Student Facilitation and Quality of Initial Postings

    Science.gov (United States)

    Ioannou, Andri; Demetriou, Skevi; Mama, Maria

    2014-01-01

    Although lots of studies have investigated collaborative knowledge construction in online courses, the factors influencing this process are yet to be fully determined. This study provides quantitative and qualitative types of evidence on how (naturally emerged) student facilitation and quality of initial postings influence collaborative knowledge…

  7. Factors Associated with Initiation of Advance Care Planning in Dementia: A Systematic Review

    NARCIS (Netherlands)

    van der Steen, J.T.; van Soest-Poortvliet, M.C.; Hallie-Heierman, M.; Onwuteaka-Philipsen, B.D.; Deliens, L.; de Boer, M.E.; Block, L.; van Uden, N.; Hertogh, C.M.P.M.; de Vet, H.C.W.

    2014-01-01

    Background: Planning ahead may be particularly relevant in dementia considering patients' cognitive decline and difficulty to predict the course of the dementia. Objective: To identify factors associated with initiation of advance care planning (ACP) regarding end-of-life issues in dementia.

  8. Age at sexual initiation and factors associated with it among youths ...

    African Journals Online (AJOL)

    Background: For behavioral as well as physiological reasons, early sexual debut increases young peoples' risk for infection with HIV and other STIs. ... of the study was to determine the median age at first sexual intercourse and the associated factors of sexual initiation among rural and urban youths (age 15- 24 years).

  9. A combined structural dynamics approach identifies a putative switch in factor VIIa employed by tissue factor to initiate blood coagulation

    DEFF Research Database (Denmark)

    Olsen, Ole H; Rand, Kasper D; Østergaard, Henrik

    2007-01-01

    ) simulations and hydrogen/deuterium exchange (HX) mass spectrometry on free and TF-bound FVIIa. The differences in conformational dynamics from MD simulations are shown to be confined to regions of FVIIa observed to undergo structural stabilization as judged by HX experiments, especially implicating activation......Coagulation factor VIIa (FVIIa) requires tissue factor (TF) to attain full catalytic competency and to initiate blood coagulation. In this study, the mechanism by which TF allosterically activates FVIIa is investigated by a structural dynamics approach that combines molecular dynamics (MD...... stability of activation loop 3. Altogether, our findings strongly support an allosteric activation mechanism initiated by the stabilization of the Leu305{163}/Phe374{225} pair, which, in turn, stabilizes activation loop 3 and the S(1) and S(3) substrate pockets, the activation pocket, and N...

  10. Synthesis, characterization and use of ATRP bifunctional initiator with trichloromethyl end-groups

    Czech Academy of Sciences Publication Activity Database

    Toman, Luděk; Janata, Miroslav; Spěváček, Jiří; Masař, Bohumil; Vlček, Petr; Látalová, Petra

    2002-01-01

    Roč. 43, č. 2 (2002), s. 18-19 ISSN 0032-3934 R&D Projects: GA ČR GA203/01/0513 Institutional research plan: CEZ:AV0Z4050913 Keywords : bifunctional initiator * ATRP polymerization * trichloromethyl end-groups Subject RIV: CD - Macromolecular Chemistry

  11. Community-based initiatives improving critical health literacy: a systematic review and meta-synthesis of qualitative evidence.

    Science.gov (United States)

    de Wit, Liesbeth; Fenenga, Christine; Giammarchi, Cinzia; di Furia, Lucia; Hutter, Inge; de Winter, Andrea; Meijering, Louise

    2017-07-20

    Critical health literacy enables older adults to make informed health decisions and take actions for the health and wellbeing of themselves and their community, within their own social and cultural context. A community-based approach has the potential to improve the critical health literacy of older adults and their communities. However, it is not clear how such initiatives consider critical health literacy. Therefore, this study explored how community-based initiatives address the critical health literacy of older adults and their communities. A systematic literature search was conducted. Two reviewers independently screened titles and abstracts, as well as the quality of the methodological and community-based elements of the studies. In addition, a meta-synthesis was carried out, consisting of a qualitative text analysis of the results sections of the 23 included studies. We identified two main themes, which are practices that contribute to the critical health literacy of older adults as well as their communities: 1) collaborative learning, and 2) social support. In these practices we identified reciprocity as a key characteristic of both co-learning and social support. This study provides the first overview of community-based initiatives that implicitly address the critical health literacy of older adults and their community. Our results demonstrate that in the context of one's own life collaborative learning and social support could contribute to people's understanding and ability to judge, sift and use health information. We therefore suggest to add these two practices to the definition of critical health literacy.

  12. Studies of the chemical basis of the origin of protein synthesis Initiation and direction of peptide growth

    Science.gov (United States)

    Mullins, D. W., Jr.; Lacey, J. C., Jr.

    1980-01-01

    The data presented in this paper show that the ease of nonenzymatic activation of carboxylic acids by ATP at pH 5 varies directly with the pKa of the carboxyl group, and is consistent with the idea that it is the protonated form of the carboxyl group which participates in the activation reaction. Consequently, since most N-blocked amino acids have higher pKas than do their unblocked forms, they are activated more readily, and it has been demonstrated that this principle applies to peptides as well, which are activated more rapidly than single amino acids. It is proposed that this fact may be partly responsible for the origin of two important features still observed in contemporary protein synthesis: (1) initiation in prokaryotes is accomplished with an N-blocked amino acid, and (2) elongation in all living systems occurs at the carboxyl end of the growing peptide.

  13. Noninjection Synthesis of CdS and Alloyed CdSxSe1−xNanocrystals Without Nucleation Initiators

    Directory of Open Access Journals (Sweden)

    Zou Yu

    2010-01-01

    Full Text Available Abstract CdS and alloyed CdSxSe1−x nanocrystals were prepared by a simple noninjection method without nucleation initiators. Oleic acid (OA was used to stabilize the growth of the CdS nanocrystals. The size of the CdS nanocrystals can be tuned by changing the OA/Cd molar ratios. On the basis of the successful synthesis of CdS nanocrystals, alloyed CdSxSe1−x nanocrystals can also be prepared by simply replacing certain amount of S precursor with equal amount of Se precursor, verified by TEM, XRD, EDX as well as UV–Vis absorption analysis. The optical properties of the alloyed CdSxSe1−x nanocrystals can be tuned by adjusting the S/Se feed molar ratios. This synthetic approach developed is highly reproducible and can be readily scaled up for potential industrial production.

  14. Papain-Catalyzed Chemoenzymatic Synthesis of Telechelic Polypeptides Using Bis(Leucine Ethyl Ester) Initiator.

    Science.gov (United States)

    Tsuchiya, Kousuke; Numata, Keiji

    2016-07-01

    In order to construct unique polypeptide architectures, a novel telechelic-type initiator with two leucine ethyl ester units is designed for chemoenzymatic polymerization. Glycine or alanine ethyl ester is chemoenzymatically polymerized using papain in the presence of the initiator, and the propagation occurs at each leucine ethyl ester unit to produce the telechelic polypeptide. The formation of the telechelic polypeptides is confirmed by (1) H NMR and MALDI-TOF mass spectroscopies. It is revealed by AFM observation that long nanofibrils are formed from the telechelic polyalanine, whereas a conventional linear polyalanine with a similar degree of polymerization shows granule-like structures. The telechelic polyglycine and polyalanine show the crystalline structures of Polyglycine II and antiparallel β-sheet, respectively. It is demonstrated that this method to synthesize telechelic-type polypeptides potentially opens up a pathway to construct novel hierarchical structures by self-assembly. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Synthesis of acrylated palm oil nanoparticles using microemulsion polymerization initiated by gamma ray

    International Nuclear Information System (INIS)

    Rida Tajau; Wan Md Zin Wan Yunus; Khairul Zaman Mohd Dahlan; Mohd Hilmi Mahmood; Kamaruddin Hashim; Sim, Flora; Sharila Muhd Faizal

    2010-01-01

    The use of microemulsion in the development of nanoparticle based on acrylated palm oil product is demonstrated. The microemulsion polymerization was initiated by gamma ray for synthesizing crosslinked nanoparticle. Polymerization of acrylated palm oil in three-component ionic microemulsions was prepared with sodium dodecyl sulphate (SDS) and water. The resulted nanoparticle, before and after initiated by gamma ray, were evaluated in terms of particle diameter, surface charge and molecular structure. Type and concentration of surfactants, monomer concentration, radiation dose and time of storage strongly affected the size, charge and size stability of the particles. For the development of new microscopic polymer acrylated palm oil can be synthesized into nano sized particle and it has potential to be developed in medical devices and controlled-drug-release-applications. (author)

  16. UV-Initiated Polymerization of Cationic Polyacrylamide: Synthesis, Characterization, and Sludge Dewatering Performance

    OpenAIRE

    Zheng, Huaili; Sun, Yongjun; Tang, Xiaomin; Tan, Mingzhuo; Ma, Jiangya; Chen, Wei; Liao, Yong

    2013-01-01

    P(AM-DAC-BA) was synthesized through copolymerization of acrylamide (AM), acryloyloxyethyl trimethyl ammonium chloride (DAC), and butylacrylate (BA) under ultraviolet (UV) initiation using response surface methodology (RSM). The influences of light intensity, illumination time, and photoinitiator concentration on the intrinsic viscosity [η] of P(AM-DAC-BA) were investigated. RSM model based on the influencing data was established for optimizing synthetic conditions. It was found that, at ligh...

  17. PNIPAAm-grafted thermoresponsive microcarriers: Surface-initiated ATRP synthesis and characterization

    International Nuclear Information System (INIS)

    Çakmak, Soner; Çakmak, Anıl S.; Gümüşderelioğlu, Menemşe

    2013-01-01

    In this study, we developed novel thermoresponsive microcarriers as a powerful tool for cell culture and tissue engineering applications. For this purpose, two types of commercially available spherical microparticles (approximately 100 μm in diameter), dextran-based Sephadex® and vinyl acetate-based VA-OH (Biosynth®), were used and themoresponsive poly(N-isopropylacrylamide) (PNIPAAm) was grafted to the beads' surfaces by surface-initiated atom transfer radical polymerization (SI-ATRP). Initially, hydroxyl groups of microbeads were reacted with 2-bromopropionyl bromide to form ATRP macroinitiator. Then, NIPAAm was successfully polymerized from the initiator attached microbeads by ATRP with CuBr/2,2′-dipyridyl, catalyst complex. Furthermore, grafted and ungrafted microbeads were characterized by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, scanning electron microscope (SEM), atomic force microscopy (AFM) and electron spectroscopy for chemical analysis (ESCA). The results of characterization studies confirmed that PNIPAAm was successfully grafted onto both dextran and vinyl acetate-based beads by means of ATRP reaction and thus, grafted microbeads gained thermoresponsive characteristics which will be evaluated for cell harvesting in further studies. Highlights: • PNIPAAm was grafted to the hydroxyl group carrying polymer beads by SI-ATRP. • Dex-g-PNIPAAm and VA-OH-g-PNIPAAm beads exhibited thermoresponsive characteristics. • They are appropriate candidates for microcarrier-facilitated cell cultures

  18. What Factors are Associated with Consumer Initiation of Shared Decision Making in Mental Health Visits?

    Science.gov (United States)

    Matthias, Marianne S; Fukui, Sadaaki; Salyers, Michelle P

    2017-01-01

    Understanding consumer initiation of shared decision making (SDM) is critical to improving SDM in mental health consultations, particularly because providers do not always invite consumer participation in treatment decisions. This study examined the association between consumer initiation of nine elements of SDM as measured by the SDM scale, and measures of consumer illness self-management and the consumer-provider relationship. In 63 mental health visits, three SDM elements were associated with self-management or relationship factors: discussion of consumer goals, treatment alternatives, and pros and cons of a decision. Limitations, implications, and future directions are discussed.

  19. Prediction of hydrological reduction factor and initial loss in urban surface runoff from small ungauged catchments

    DEFF Research Database (Denmark)

    Arnbjerg-Nielsen, K.; Harremoës, P.

    1996-01-01

    An advanced runoff model is compared to a simple one employing only a runoff coefficient and a regression parameter allowing for initial loss. The present study shows that the more detailed description of the runoff processes cannot be justified due to the uncertainty from using only one gauge...... in a catchment for the description of the rain input. A significant variation of the two parameters from one catchment to another has been found and the uncertainty of the two variables are evaluated. The uncertainty of the hydrological reduction factor and the initial loss should be taken into account...

  20. Crystal structure of catalytic domain of the initiation factor 2B epsilon subunit

    DEFF Research Database (Denmark)

    Boesen, Thomas; Mohammad, Sarah S.; Pavitt, Graham D.

    , surface exposed acidic patch which might interact with the lysine boxes of eIF2β. Interestingly, Tryptophan 699 was found to be solvent exposed and involved in crystal packing. This residue could possibly be important for the specific interaction with eIF2β. Furthermore, the structure shows the location......CRYSTAL STRUCTURE OF CATALYTIC DOMAIN OF THE INITIATION FACTOR 2B EPSILON SUBUNIT Thomas Boesen1,Sarah S. Mohammad2, Graham Pavitt2, and Gregers R. Andersen1* 1Department of Molecular Biology, University of Aarhus, Gustav Wieds Vej 10C, DK-8000 Århus C, Denmark 2Department of Biomolecular Sciences......, UMIST, PO Box 88, Manchester, M60 1QD, UK Eukaryotic initiation factor 2B (eIF2B) is the exchange factor of initiation factor 2 (eIF2) and catalyses the reaction where GDP bound to eIF2 is exchanged for GTP, a crucial step in translation. The crystal structure of the C-terminal catalytic domain of the e...

  1. Synthesis of 2-18F-fluoroisonicotinic acid hydrazide and initial biological evaluation

    International Nuclear Information System (INIS)

    Al Jammaz, I.; Abu Durrah, B.; Amartey, J.

    2002-01-01

    Isonicotinic acid hydrazide (isonizide) is one of the most effective agents in tuberculosis therapy. This agent rapidly permeates the bacterial cell membrane via passive diffusion. The central nervous system tuberculosis is being observed in patients who are intravenous drug abusers, with AIDS and AIDS-related complex. Therefore, radiopharmaceuticals for diagnosis of tuberculosis may become important. Very few attempts have been made to develop isonicotinic acid and derivatives for the same application. As part of an on-going research effort to develop radiotracers for fluorination of proteins and peptides via prosthetic groups approach, we have synthesized ethyl 2-[18F]-fluoroisonicotinate and 2-[18F]-fluoroisonicotinic acid hydrazide. The synthetic approach starts from treatment of ethyl-2-(trimethylammonium)-isonicotinate precursor using no-carrier-added radiofluoride produced by the 18O(p,n)18F nuclear reaction on 18O-enriched (95 %) water and Kryptofix 222 as nucleophilic catalyst in anhydrous acetonitrile at 100 0 C, gave ethyl 2-[18F]-fluoroisonicotinate in greater than 90% radiochemical yield (decay corrected) within two minutes reaction time. The ether extract of fluorinated ethylester evaporated and residue was re-dissolved in ethanol and treated with hydrazine for 15 minutes in boiling water to obtain 2-[18F]-fluoroisonicotinic acid hydrazide in excellent radiochemical yield. The overall radiochemical yield was greater that 70% with total synthesis time of approximately one hour. This synthetic approach hold considerable promise as a rapid and simple method for fluorination of radiopharmaceuticals of high radiochemical yield. Biological evaluation was performed in normal mice. The data obtained shown that the lungs appear to retain some activity that someone may presume that such radiotracer maybe useful in detection of tuberculosis

  2. Initial synthesis of area 13 239Pu data and other statistical analyses

    International Nuclear Information System (INIS)

    Gilbert, R.O.; Eberhardt, L.L.

    1976-02-01

    An initial effort is made here to synthesize the 239-240 Pu data currently available from Area 13 (Project 57). Plutonium concentrations for soil, vegetation, small vertebrates, and various tissues in beef cattle (grazed on the Pu contaminated vegetation) are plotted on a single graph for visual comparison. Hypothetical 239-240 Pu concentrations for lungs, skeletal bone, and kidney of a Standard Man assumed to live in and obtain most of his food from the area are also plotted. These hypothetical values were obtained using results from the plutonium transport and dose estimation model of Martin and Bloom (1975)

  3. Initial synthesis of area 13 /sup 239/Pu data and other statistical analyses

    Energy Technology Data Exchange (ETDEWEB)

    Gilbert, R.O.; Eberhardt, L.L.

    1976-02-01

    An initial effort is made here to synthesize the /sup 239 -240/Pu data currently available from Area 13 (Project 57). Plutonium concentrations for soil, vegetation, small vertebrates, and various tissues in beef cattle (grazed on the Pu contaminated vegetation) are plotted on a single graph for visual comparison. Hypothetical /sup 239 -240/Pu concentrations for lungs, skeletal bone, and kidney of a Standard Man assumed to live in and obtain most of his food from the area are also plotted. These hypothetical values were obtained using results from the plutonium transport and dose estimation model of Martin and Bloom (1975).

  4. Factors influencing timely initiation and completion of gestational diabetes mellitus screening and diagnosis

    DEFF Research Database (Denmark)

    Nielsen, Karoline Kragelund; Rheinländer, Thilde; Kapur, Anil

    2017-01-01

    -structured interviews with 30 pregnant women and nine health care providers were conducted. Data was analysed using qualitative content analysis. RESULTS: There were significant differences in the process of GDM screening and diagnosis in the urban and rural settings. Several factors hindering or facilitating timely...... in time to initiate further action. All these steps and requirements were influenced by factors within and outside the health system such as getting right information from health care providers, clinic timings, characteristics of the test, availability of transport, social network and support, and social...

  5. Preliminary Investigation Of Emirati Women Entrepreneurship In The UAE Motivating Factors Challenges And Government Initiatives

    Directory of Open Access Journals (Sweden)

    Mohammad Rehan Shahnawaz

    2015-08-01

    Full Text Available Abstract Purpose The purpose of this research is to conduct an in depth preliminary investigation of the Emirati Women Entrepreneurship in the UAE in terms of the factors motivating the Emirati women to engage in the entrepreneurial activities challenges and issues faced by them in that process and initiatives taken by the government of UAE in overcoming those challenges and in encouraging promoting and safeguarding their interests. Methodology This research is an exploratory one due to the fact that the topic of the research strongly requires an in depth analysis or investigation of the underlying motivating factors challenges and issues and the government initiatives taken on behalf of Emirati women entrepreneurs. The research has used qualitative content analysis technique in which the existing literature secondary data on women and Emirati women entrepreneurship was gathered and discussed to serve the purpose of the research such as from other published researches internet searches and books. DiscussionsFindings The research explored an array of factors motivating the Emirati women towards entrepreneurship and the challenges and issues they come across in that process. The motivating factors were divided into positive and negative factors with main emphasis on the positive factors. Among the positive motivating factors were the Emiratization change in the organizational culture and beliefs relaxation of social and cultural structures inde-pendence and self-improvement and development. The negative motivating factors were the necessity unacceptable working conditions inflexible work hours wage gap between males and females and job frustrations. The major challenges and issues they usually come across are traditions cultural religious and social restrictions lack of managerial experience and basic business knowledge low self-confidence and determination male prejudice stereotyping and preconception minimal networking gender based promotional

  6. Factors attributing to initiation of tobacco use in adolescent students of Moradabad, (UP) India

    OpenAIRE

    Ravishankar T; Nagarajappa Ramesh

    2009-01-01

    Background: Tobacco consumption is a major health menace owing to its widespread use particularly among adolescents. Owing to the presence of impressionable, curious minds, adolescents are highly prone to a number of influences within and outside home, leading them to experiment with tobacco. The addictive nature of tobacco is potent enough to turn these experimental users to addicts. Objectives: To identify the prominent factors leading to initiation of tobacco use among adolescents of Mo...

  7. UV-Initiated Polymerization of Cationic Polyacrylamide: Synthesis, Characterization, and Sludge Dewatering Performance

    Directory of Open Access Journals (Sweden)

    Huaili Zheng

    2013-01-01

    Full Text Available P(AM-DAC-BA was synthesized through copolymerization of acrylamide (AM, acryloyloxyethyl trimethyl ammonium chloride (DAC, and butylacrylate (BA under ultraviolet (UV initiation using response surface methodology (RSM. The influences of light intensity, illumination time, and photoinitiator concentration on the intrinsic viscosity [η] of P(AM-DAC-BA were investigated. RSM model based on the influencing data was established for optimizing synthetic conditions. It was found that, at light intensity 1491.67 μw·cm−2, illumination time 117.89 min, and photoinitiator concentration 0.60‰, there was a better material performance achieved. Thus P(AM-DAC-BA prepared under the above conditions showed excellent dewatering performance that, with 40 mg·L−1 P(AM-DAC-BA at pH 7, the residual turbidity of supernatant and the dry solid content were up to 38 NTU, 28.5%, respectively.

  8. UV-Initiated polymerization of cationic polyacrylamide: synthesis, characterization, and sludge dewatering performance.

    Science.gov (United States)

    Zheng, Huaili; Sun, Yongjun; Tang, Xiaomin; Tan, Mingzhuo; Ma, Jiangya; Chen, Wei; Liao, Yong

    2013-01-01

    P(AM-DAC-BA) was synthesized through copolymerization of acrylamide (AM), acryloyloxyethyl trimethyl ammonium chloride (DAC), and butylacrylate (BA) under ultraviolet (UV) initiation using response surface methodology (RSM). The influences of light intensity, illumination time, and photoinitiator concentration on the intrinsic viscosity [η] of P(AM-DAC-BA) were investigated. RSM model based on the influencing data was established for optimizing synthetic conditions. It was found that, at light intensity 1491.67  μ w·cm(-2), illumination time 117.89 min, and photoinitiator concentration 0.60‰, there was a better material performance achieved. Thus P(AM-DAC-BA) prepared under the above conditions showed excellent dewatering performance that, with 40 mg·L(-1) P(AM-DAC-BA) at pH 7, the residual turbidity of supernatant and the dry solid content were up to 38 NTU, 28.5%, respectively.

  9. Synthesis of uranium metal using laser-initiated reduction of uranium tetrafluoride by calcium metal

    International Nuclear Information System (INIS)

    West, M.H.; Martinez, M.M.; Nielsen, J.B.; Court, D.C.; Appert, Q.D.

    1995-09-01

    Uranium metal has numerous uses in conventional weapons (armor penetrators) and nuclear weapons. It also has application to nuclear reactor designs utilizing metallic fuels--for example, the former Integral Fast Reactor program at Argonne National Laboratory. Uranium metal also has promise as a material of construction for spent-nuclear-fuel storage casks. A new avenue for the production of uranium metal is presented that offers several advantages over existing technology. A carbon dioxide (CO 2 ) laser is used to initiate the reaction between uranium tetrafluoride (UF 4 ) and calcium metal. The new method does not require induction heating of a closed system (a pressure vessel) nor does it utilize iodine (I 2 ) as a chemical booster. The results of five reductions of UF 4 , spanning 100 to 200 g of uranium, are evaluated, and suggestions are made for future work in this area

  10. Initiative Within the Philosophy of Auftragstaktik: Determining Factors of the Understanding of Initiative in the German Army, 1806-1955

    Science.gov (United States)

    2015-01-01

    of Initiative in the German Army, 1806-1955 Martin Sonnenberger, Lieutenant Colonel (GS), German Army Diplom Kaufmann (univ), Universitat Bundeswehr ...understanding of tactical and operational initiative against the background of the current doctrinal framework of Auftragstaktik as defined by the Bundeswehr ...As far as US doctrinal terms equate to the definition and understanding in the Bundeswehr concept of Auftragstaktik, they are used for ease of

  11. Phylogenomically guided identification of industrially relevant GH1 β-glucosidases through DNA synthesis and nanostructure-initiator mass spectrometry.

    Science.gov (United States)

    Heins, Richard A; Cheng, Xiaoliang; Nath, Sangeeta; Deng, Kai; Bowen, Benjamin P; Chivian, Dylan C; Datta, Supratim; Friedland, Gregory D; D'Haeseleer, Patrik; Wu, Dongying; Tran-Gyamfi, Mary; Scullin, Chessa S; Singh, Seema; Shi, Weibing; Hamilton, Matthew G; Bendall, Matthew L; Sczyrba, Alexander; Thompson, John; Feldman, Taya; Guenther, Joel M; Gladden, John M; Cheng, Jan-Fang; Adams, Paul D; Rubin, Edward M; Simmons, Blake A; Sale, Kenneth L; Northen, Trent R; Deutsch, Samuel

    2014-09-19

    Harnessing the biotechnological potential of the large number of proteins available in sequence databases requires scalable methods for functional characterization. Here we propose a workflow to address this challenge by combining phylogenomic guided DNA synthesis with high-throughput mass spectrometry and apply it to the systematic characterization of GH1 β-glucosidases, a family of enzymes necessary for biomass hydrolysis, an important step in the conversion of lignocellulosic feedstocks to fuels and chemicals. We synthesized and expressed 175 GH1s, selected from over 2000 candidate sequences to cover maximum sequence diversity. These enzymes were functionally characterized over a range of temperatures and pHs using nanostructure-initiator mass spectrometry (NIMS), generating over 10,000 data points. When combined with HPLC-based sugar profiling, we observed GH1 enzymes active over a broad temperature range and toward many different β-linked disaccharides. For some GH1s we also observed activity toward laminarin, a more complex oligosaccharide present as a major component of macroalgae. An area of particular interest was the identification of GH1 enzymes compatible with the ionic liquid 1-ethyl-3-methylimidazolium acetate ([C2mim][OAc]), a next-generation biomass pretreatment technology. We thus searched for GH1 enzymes active at 70 °C and 20% (v/v) [C2mim][OAc] over the course of a 24-h saccharification reaction. Using our unbiased approach, we identified multiple enzymes of different phylogentic origin with such activities. Our approach of characterizing sequence diversity through targeted gene synthesis coupled to high-throughput screening technologies is a broadly applicable paradigm for a wide range of biological problems.

  12. Overall impact of speed-related initiatives and factors on crash outcomes.

    Science.gov (United States)

    D'Elia, A; Newstead, S; Cameron, M

    2007-01-01

    From December 2000 until July 2002 a package of speed-related initiatives and factors took place in Victoria, Australia. The broad aim of this study was to evaluate the overall impact of the package on crash outcomes. Monthly crash counts and injury severity proportions were assessed using Poisson and logistic regression models respectively. The model measured the overall effect of the package after adjusting as far as possible for non-speed road safety initiatives and socio-economic factors. The speed-related package was associated with statistically significant estimated reductions in casualty crashes and suggested reductions in injury severity with trends towards increased reductions over time. From December 2000 until July 2002, three new speed enforcement initiatives were implemented in Victoria, Australia. These initiatives were introduced in stages and involved the following key components: More covert operations of mobile speed cameras, including flash-less operations; 50% increase in speed camera operating hours; and lowering of cameras' speed detection threshold. In addition, during the period 2001 to 2002, the 50 km/h General Urban Speed Limit (GUSL) was introduced (January 2001), there was an increase in speed-related advertising including the "Wipe Off 5" campaign, media announcements were made related to the above enforcement initiatives and there was a speeding penalty restructure. The above elements combine to make up a package of speed-related initiatives and factors. The package represents a broad, long term program by Victorian government agencies to reduce speed based on three linked strategies: more intensive Police enforcement of speed limits to deter potential offenders, i.e. the three new speed enforcement initiatives just described - supported by higher penalties; a reduction in the speed limit on local streets throughout Victoria from 60 km/h to 50 km/h; and provision of information using the mass media (television, radio and billboard) to

  13. Peroxydisulfate initiated synthesis of potato starch-graft-poly(acrylonitrile under microwave irradiation

    Directory of Open Access Journals (Sweden)

    2007-01-01

    Full Text Available Potato starch-graft-poly(acrylonitrile could be efficiently synthesized using small concentration of ammonium peroxydisulfate (0.0014M in aqueous medium under microwave irradiation. A representative microwave synthesized graft copolymer was characterized using Fourier Transform Infrared Spectroscopy, X-ray Diffraction, Scanning Electron Microscopy and Thermogravimetric Analysis. Under microwave conditions oxygen removal from the reaction vessel was not required and the graft copolymer was obtained in high yield using very small amount of ammonium peroxydisulfate, however using the same amount of ammonium peroxydisulfate (0.0014M on thermostatic water bath no grafting was observed up to 98°C (even in inert atmosphere. Raising the concentration of the initiator to 0.24 M resulted into 10% grafting at 50 °C but in inert atmosphere.The viscosity/shear stability of the grafted starch (aqueous solution and water/saline retention ability of the microwave synthesized graft copolymer were also studied and compared with that of the native potato starch.

  14. Initial study - compilation and synthesis of knowledge about energy crops from field to energy production

    Energy Technology Data Exchange (ETDEWEB)

    Berg, Magnus; Bubholz, Monika; Forsberg, Maya; Myringer, Aase; Palm, Ola; Roennbaeck, Marie; Tullin, Claes

    2007-11-15

    Energy crops constitute an yet not fully utilised potential as fuel for heating and power production. As competition for biomass increases interest in agricultural fuels such as straw, energy grain, willow, reed canary grass and hemp is increasing. Exploiting the potential for energy crops as fuels will demand that cultivation and harvest be coordinated with transportation, storage and combustion of the crops. Together, Vaermeforsk and the Swedish Farmers' Foundation for Agricultural Research (SLF), have taken the initiative to a common research programme. The long-term aim of the programme is to increase production and utilisation of bioenergy from agriculture to combustion for heat and power production in Sweden. The vision is that during the course of the 2006 - 2009 programme, decisive steps will be taken towards a functioning market for biofuels for bioenergy from agriculture. This survey has compiled and synthesised available knowledge and experiences about energy crops from field to energy production. The aim has been to provide a snapshot of knowledge today, to identify knowledge gaps and to synthesise knowledge we have today into future research needs. A research plan proposal has been developed for the research programme

  15. Factors associated with delays in treatment initiation after tuberculosis diagnosis in two districts of India.

    Directory of Open Access Journals (Sweden)

    Durba Paul

    Full Text Available BACKGROUND: Excessive time between diagnosis and initiation of tuberculosis (TB treatment contributes to ongoing TB transmission and should be minimized. In India, Revised National TB Control Programme (RNTCP focuses on indicator start of treatment within 7 days of diagnosis for patients with sputum smear-positive PTB for monitoring DOTS implementation. OBJECTIVES: To determine length of time between diagnosis and initiation of treatment and factors associated with delays of more than 7 days in smear-positive pulmonary TB. METHODS: Using existing programme records such as the TB Register, treatment cards, and the laboratory register, we conducted a retrospective cohort study of all patients with smear-positive pulmonary TB registered from July-September 2010 in two districts in India. A random sample of patients with pulmonary TB who experienced treatment delay of more than 7 days was interviewed using structured questionnaire. RESULTS: 2027 of 3411 patients registered with pulmonary TB were smear-positive. 711(35% patients had >7 days between diagnosis and treatment and 262(13% had delays >15 days. Mean duration between TB diagnosis and treatment initiation was 8 days (range = 0-128 days. Odds of treatment delay >7 days was 1.8 times more likely among those who had been previously treated (95% confidence interval [CI] 1.5-2.3 and 1.6 (95% CI 1.3-1.8 times more likely among those diagnosed in health facilities without microscopy centers. The main factors associated with a delay >7 days were: patient reluctance to start a re-treatment regimen, patients seeking second opinions, delay in transportation of drugs to the DOT centers and delay in initial home visits. To conclude, treatment delay >7 days was associated with a number of factors that included history of previous treatment and absence of TB diagnostic services in the local health facility. Decentralized diagnostic facilities and improved referral procedures may reduce such treatment

  16. Factor Analysis on Criteria Affecting Lean Retrofit for Energy Efficient Initiatives in Higher Learning Institution Buildings

    Directory of Open Access Journals (Sweden)

    Abidin Nur IzieAdiana

    2017-01-01

    Full Text Available The expansion of Higher Learning Institution (HLI is a global concerns on energy demand due to campus act like a small city. Intensive mode of operation of a building is correlated to the energy utilization. Improvement in the current energy efficiency is crucial effort to minimize the environmental effect through minimisation of energy in operation by retrofitting and upgrade the existing building system or components to be more efficient. Basically, there are three recommended steps for the improvement known as lean initiatives, green technology and clean energy in response to becoming zero energy solutions for building. The deliberation of this paper is aimed to highlight the criteria affecting in retrofitting of existing building in HLI with lean initiatives in order to achieve energy efficiency and reduction of energy comsumption. Attention is devoted to reviewing the lean energy retrofitting initiatives criteria for daylighting (side lighting, daylighting (skylight and glazing. The questionnaire survey was employed and distributed to the architects who has an expertise in green building design. Factor analysis was adopted as a method of analysis by using Principal Component with Varimax Rotation. The result is presented through summarizing the sub-criteria according to its importance with a factor loading 0.50 and above. The result found that majority of the criteria developed achieved the significant factor loading value and in accordance with the protocal of analysis. In conclusion the results from analysis of this paper assists the stakeholders in assessing the significant criteria based on the desired lean energy retrofitting initiatives and also provides a huge contribution for future planning improvement in existing buildings to become an energy efficient building.

  17. Design, synthesis, and initial evaluation of D-glyceraldehyde crosslinked gelatin-hydroxyapatite as a potential bone graft substitute material

    Science.gov (United States)

    Florschutz, Anthony Vatroslav

    Utilization of bone grafts for the treatment of skeletal pathology is a common practice in orthopaedic, craniomaxillofacial, dental, and plastic surgery. Autogenous bone graft is the established archetype but has disadvantages including donor site morbidity, limited supply, and prolonging operative time. In order to avoid these and other issues, bone graft substitute materials are becoming increasingly prevalent among surgeons for reconstructing skeletal defects and arthrodesis applications. Bone graft substitutes are biomaterials, biologics, and guided tissue/bone regenerative devices that can be used alone or in combinations as supplements or alternatives to autogenous bone graft. There is a growing interest and trend to specialize graft substitutes for specific indications and although there is good rationale for this indication-specific approach, the development and utility of a more universal bone graft substitute may provide a better answer for patients and surgeons. The aim of the present research focuses on the design, synthesis, and initial evaluation of D-glyceraldehyde crosslinked gelatin-hydroxyapatite composites for potential use as a bone graft substitutes. After initial establishment of rational material design, gelatinhydroxyapatite scaffolds were fabricated with different gelatin:hydroxyapatite ratios and crosslinking concentrations. The synthesized scaffolds were subsequently evaluated on the basis of their swelling behavior, porosity, density, percent composition, mechanical properties, and morphology and further assessed with respect to cell-biomaterial interaction and biomineralization in vitro. Although none of the materials achieved mechanical properties suitable for structural graft applications, a reproducible material design and synthesis was achieved with properties recognized to facilitate bone formation. Select scaffold formulations as well as a subset of scaffolds loaded with recombinant human bone morphogenetic protein-2 were

  18. Initial factors predicting rebleeding and death in bleeding peptic ulcer disease.

    Science.gov (United States)

    Al-Akeely, Mohammed H; Alam, Mohammed K; Al-Salamah, Saleh M; Abdu, Mahmood A; Al-Teimi, Ibrahim N; Mohammed, Abdulmajeed A

    2004-05-01

    Bleeding peptic ulcer constitutes approximately half of the cases admitted with upper gastrointestinal bleeding. Although the bleeding episode stops spontaneously in most of them, rebleeding occurs in as much as 10-30% of them and has a mortality rate of 5-10%. In this study, we have evaluated the possible significant predictors associated with this adverse outcome. The records of 205 patients admitted to gastrointestinal bleeding unit (GIBU) in Riyadh Central Hospital, during the period May 1996 through to April 1999, with endoscopic confirmed diagnosis of bleeding peptic ulcer disease were reviewed for demography, clinical presentation, hematology, biochemistry, initial blood pressure, nasogastric lavage color, co-morbid disease and endoscopic findings. All the significant factors found initially (Pulcer was the source of bleeding in 84%. Endoscopy was performed in all patients within 24 hours of admission. Only 15% were actively bleeding at the time of initial endoscopy. Thirty-six patients (17%) rebelled, majority within 72 hours of initial hemostasis. Overall, 11 patients (5%) died, 6 of them were rebleeders. Initial presentation of systolic blood pressure ulcer in endoscopy were independent predictors of rebleeding while initial systolic blood pressure 60-years were independent predictors of mortality. Improvement of outcome in patients with bleeding peptic ulcer disease can be achieved by early detection of those patients who are at risk of adverse outcome. Patients with the above mentioned independent predictors of rebleeding and mortality are best managed in the intensive care unit with endoscopic hemostasis and proton pump inhibitor (PPI) therapy for a minimum of 5-days of admission.

  19. AUU-to-AUG mutation in the initiator codon of the translation initiation factor IF3 abolishes translational autocontrol of its own gene (infC) in vivo.

    Science.gov (United States)

    Butler, J S; Springer, M; Grunberg-Manago, M

    1987-06-01

    We previously showed that Escherichia coli translation initiation factor IF3 regulates the expression of its own gene infC at the translational level in vivo. Here we create two alterations in the infC gene and test their effects on translational autocontrol of infC expression in vivo by measuring beta-galactosidase activity expressed from infC-lacZ gene fusions under conditions of up to 4-fold derepression or 3-fold repression of infC expression. Replacement of the infC promoter with the trp promoter deletes 120 nucleotides of the infC mRNA 5' to the translation initiation site without affecting autogenous translational control. Mutation of the unusual AUU initiator codon of infC to the more common AUG initiator codon abolishes translation initiation factor IF3-dependent repression and derepression of infC expression in vivo. These results establish the AUU initiator codon of infC as an essential cis-acting element in autogenous translational control of translation initiation factor IF3 expression in vivo.

  20. Long-term course of Crohn's disease in Japan: Incidence of complications, cumulative rate of initial surgery, and risk factors at diagnosis for initial surgery.

    Science.gov (United States)

    Sato, Yuho; Matsui, Toshiyuki; Yano, Yutaka; Tsurumi, Kozue; Okado, Yuki; Matsushima, Yu; Koga, Akihiro; Takahashi, Haruhiko; Ninomiya, Kazeo; Ono, Yoichiro; Takatsu, Noritaka; Beppu, Takahiro; Nagahama, Takashi; Hisabe, Takashi; Takaki, Yasuhiro; Hirai, Fumihito; Yao, Kenshi; Higashi, Daijiro; Futami, Kitaro; Washio, Masakazu

    2015-12-01

    Intestinal complications of stenosis or fistula may occur during the course of Crohn's disease (CD), and surgery is performed in a fair number of patients. The risk factors for initial surgery in a Japanese hospital-based cohort of CD patients were evaluated. This study was a single-center, retrospective, cohort study. The subjects were 520 patients who underwent inpatient and outpatient treatment at our hospital, had a definitive diagnosis of CD, and no previous surgery. Three parameters were investigated: (i) cumulative incidence of stenosis and fistula; (ii) cumulative rate of initial surgery for each disease type; and (iii) risk factors at diagnosis for initial surgery. (i) Stenosis and fistula increased with time, with stenosis or fistula appearing in about half of the patients after 5 years. (ii) The cumulative rate of initial surgery was about 50% after 10 years. (iii) The patient factors at diagnosis of current smoker, upper gastrointestinal disease, stricturing, penetrating, moderate to severe stenosis of the jejunum, moderate to severe stenosis of the ileum, and moderate to severe stenosis of the terminal ileum were risk factors for initial surgery. Stenosis or fistula appeared in about half of the patients after 5 years from diagnosis. When upper gastrointestinal disease or complicated small intestinal lesions are seen at the time of diagnosis, the cumulative rate of initial surgery is significantly higher. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  1. Decisions to initiate involuntary commitment: the role of intensive community services and other factors.

    Science.gov (United States)

    McGarvey, Elizabeth Lloyd; Leon-Verdin, MaGuadalupe; Wanchek, Tanya Nicole; Bonnie, Richard J

    2013-02-01

    This study examined the predictors of actions to initiate involuntary commitment of individuals experiencing a mental health crisis. Emergency services clinicians throughout Virginia completed a questionnaire following each face-to-face evaluation of individuals experiencing a mental health crisis. Over a one-month period in 2007, a total of 2,624 adults were evaluated. Logistic hierarchical multiple regression was used to analyze the relationship between demographic, clinical, and service-related variables and outcomes of the emergency evaluations. Several factors predicted 84% of the actions taken to initiate involuntary commitment. These included unavailability of alternatives to hospitalization, such as temporary housing or residential crisis stabilization; evaluation of the client in a hospital emergency room or police station or while in police custody; current enrollment in treatment; and clinical factors related to the commitment criteria, including risk of self-harm or harm to others, acuity and severity of the crisis, and current drug abuse or dependence. A lack of intensive community-based treatment and support in lieu of hospitalization accounted for a significant portion of variance in actions to initiate involuntary commitment. Comprehensive community services and supports for individuals experiencing mental health crises may reduce the rate of involuntary hospitalization. There is a need to enrich intensive community mental health services and supports and to evaluate the impact of these enhancements on the frequency of involuntary mental health interventions.

  2. Individual- and contextual-level factors associated with client-initiated HIV testing

    Directory of Open Access Journals (Sweden)

    Claudia Renata dos Santos Barros

    Full Text Available ABSTRACT: Background: Knowing the reasons for seeking HIV testing is central for HIV prevention. Despite the availability of free HIV counseling and testing in Brazil, coverage remains lacking. Methods: Survey of 4,760 respondents from urban areas was analyzed. Individual-level variables included sociodemographic characteristics; sexual and reproductive health; HIV/AIDS treatment knowledge and beliefs; being personally acquainted with a person with HIV/AIDS; and holding discriminatory ideas about people living with HIV. Contextual-level variables included the Human Development Index (HDI of the municipality; prevalence of HIV/AIDS; and availability of local HIV counseling and testing (CT services. The dependent variable was client-initiated testing. Multilevel Poisson regression models with random intercepts were used to assess associated factors. Results: Common individual-level variables among men and women included being personally acquainted with a person with HIV/AIDS and age; whereas discordant variables included those related to sexual and reproductive health and experiencing sexual violence. Among contextual-level factors, availability of CT services was variable associated with client-initiated testing among women only. The contextual-level variable “HDI of the municipality” was associated with client-initiated testing among women. Conclusion: Thus, marked gender differences in HIV testing were found, with a lack of HIV testing among married women and heterosexual men, groups that do not spontaneously seek testing.

  3. Cannabinoid Modulation of Eukaryotic Initiation Factors (eIF2α and eIF2B1 and Behavioral Cross-Sensitization to Cocaine in Adolescent Rats

    Directory of Open Access Journals (Sweden)

    Philippe A. Melas

    2018-03-01

    Full Text Available Summary: Reduced eukaryotic Initiation Factor 2 (eIF2α phosphorylation (p-eIF2α enhances protein synthesis, memory formation, and addiction-like behaviors. However, p-eIF2α has not been examined with regard to psychoactive cannabinoids and cross-sensitization. Here, we find that a cannabinoid receptor agonist (WIN 55,212-2 mesylate [WIN] reduced p-eIF2α in vitro by upregulating GADD34 (PPP1R15A, the recruiter of protein phosphatase 1 (PP1. The induction of GADD34 was linked to ERK/CREB signaling and to CREB-binding protein (CBP-mediated histone hyperacetylation at the Gadd34 locus. In vitro, WIN also upregulated eIF2B1, an eIF2 activator subunit. We next found that WIN administration in vivo reduced p-eIF2α in the nucleus accumbens of adolescent, but not adult, rats. By contrast, WIN increased dorsal striatal levels of eIF2B1 and ΔFosB among both adolescents and adults. In addition, we found cross-sensitization between WIN and cocaine only among adolescents. These findings show that cannabinoids can modulate eukaryotic initiation factors, and they suggest a possible link between p-eIF2α and the gateway drug properties of psychoactive cannabinoids. : Melas et al. show that psychoactive cannabinoids modulate levels of two eukaryotic initiation factors (eIF2α and eIF2B1 known to be involved in protein synthesis, memory formation, and drug sensitivity. Cannabinoid modulation of eIF2α in vivo is only observed in adolescent animals, and is associated with cross-sensitization to cocaine. Keywords: drug use, addiction, cannabis, marijuana, cocaine, epigenetics, eIF2a, CREB, GADD34, gateway drugs

  4. Non-modifiable worker and workplace risk factors contributing to workplace absence: A stakeholder-centred synthesis of systematic reviews.

    Science.gov (United States)

    White, Marc I; Wagner, Shannon L; Schultz, Izabela Z; Murray, Eleanor; Bradley, Susan M; Hsu, Vernita; McGuire, Lisa; Schulz, Werner

    2015-01-01

    Workplace stakeholders report the identification and translation of relevant high quality research to inform workplace disability policy and practice is a challenge. The present study engaged academic and community stakeholders in conducting a best evidence-synthesis to identify non-modifiable risk and protective worker and workplace factors impacting work-related absence across a variety of health conditions. To identify non-modifiable worker and workplace disability risk and protective factors impacting work-related absence across common health conditions. The research team searched Medline, Embase, CINAHL, The Cochrane Library, PsycINFO, BusinessSource-Complete, and ABI/Inform from 2000 to 2011. Quantitative, qualitative, or mixed methods systematic reviews of work-focused population were considered for inclusion. Two or more reviewers independently reviewed articles for inclusion and methodological screening. The search strategy, including expert input and grey literature, led to the identification of 2,467 unique records. From this initial search, 2325 were eliminated by title or abstract review, 142 articles underwent comprehensive review to assess for inclusion, 26 systematic reviews met eligibility criteria for this synthesis. For non-modifiable worker and workplace factors we found consistent evidence across two or more health conditions for increased risk of disability in situations where workers experience lower education, older age, emotional distress, poor personal functioning, decreased physical functioning, psychological symptoms, overweight status, and greater sick leave history. Heterogeneity of existing literature due to differences in outcome measures, definitions and research designs limited ability to assess effect size and results reflect findings limited to English-language papers.

  5. Prevalence of marijuana use at college entry and risk factors for initiation during freshman year.

    Science.gov (United States)

    Suerken, Cynthia K; Reboussin, Beth A; Sutfin, Erin L; Wagoner, Kimberly G; Spangler, John; Wolfson, Mark

    2014-01-01

    Marijuana is currently the most commonly used drug on college campuses. Marijuana use among college students is increasing, and many students begin using marijuana during college. The goal of this study was to investigate predictors of lifetime marijuana use at college entry and initiation during freshman year. We used responses from the first two semesters of a longitudinal study of 3146 students from 11 colleges in North Carolina and Virginia. Random-effects logistic regression models were constructed to identify factors that predict lifetime marijuana use at college entry and initiation during freshman year. Nearly 30% of students reported ever having used marijuana at college entry. Among students who had never used marijuana prior to college, 8.5% initiated use during freshman year. In multivariable logistic regression models, having at least $100 per month in spending money; attending church rarely or never; current use of cigarettes, alcohol, and hookah tobacco; lifetime use of other illicit drugs; and a higher propensity toward sensation seeking were associated with a higher likelihood of having used marijuana at least once at college entry. Hispanic ethnicity, living on campus, and current use of cigarettes and alcohol were associated with a higher likelihood of initiating marijuana use during freshman year. These results have implications for targeting substance abuse prevention programs on college campuses.

  6. Structure and functions of the translation initiation factor eIF4E and its role in cancer development and treatment.

    Science.gov (United States)

    Piserà, Arianna; Campo, Adele; Campo, Salvatore

    2018-01-20

    In eukaryotic cells, protein synthesis is a complex and multi-step process that has several mechanisms to start the translation including cap-dependent and cap-independent initiation. The translation control of eukaryotic gene expression occurs principally at the initiation step. In this context, it is critical that the eukaryotic translation initiation factor eIF4E bind to the 7-methylguanosine (m7G) cap present at the 5'-UTRs of most eukaryotic mRNAs. Combined with other initiation factors, eIF4E mediates the mRNA recruitment on ribosomes to start the translation. Moreover, the eIF4E nuclear bodies are involved in the export of specific mRNAs from the nucleus to the cytoplasm. In this review, we focus on the eIF4E structure and its physiological functions, and describe the role of eIF4E in cancer development and progression and the current therapeutic strategies to target eIF4E. Copyright © 2018 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

  7. Factors Related to Cigarette Smoking Initiation and Use among College Students

    Directory of Open Access Journals (Sweden)

    Ebert Sheryl

    2005-01-01

    Full Text Available Abstract The purpose of this cross-sectional study was to examine the impact of personality factors (neuroticism, extraversion, openness, agreeableness, and conscientiousness, cognitive factors (sense of coherence and self-efficacy, coping resources (family and friend social support and demographic factors (gender and ethnicity on cigarette smoking behaviors (initiation, frequency, and amount of cigarette smoking among college students. A total of 161 U.S. college students, aged 18–26, who enrolled in an introductory psychology course completed self-report questionnaires. The majority of the students had tried smoking (55%; among those who had tried, 42% were current smokers. The majority (77% who had smoked a whole cigarette did so at age 16 years or younger. Students who reported lower levels of conscientiousness and self-efficacy had a greater likelihood to had tried cigarette smoking. Also, students who had lower levels of self-efficacy reported smoking more frequently and greater quantities of cigarettes than students with higher levels of self-efficacy. Self-efficacy was the most significant predictor of smoking behaviors. Health promotion programs focused on self-efficacy may be an effective tool for reducing the initiation, frequency, and amount of cigarette smoking among college students.

  8. Factors Associated with Gender-Affirming Surgery and Age of Hormone Therapy Initiation Among Transgender Adults

    Science.gov (United States)

    Beckwith, Noor; Reisner, Sari L.; Zaslow, Shayne; Mayer, Kenneth H.; Keuroghlian, Alex S.

    2017-01-01

    Abstract Purpose: Gender-affirming surgeries and hormone therapy are medically necessary treatments to alleviate gender dysphoria; however, significant gaps exist in the research and clinical literature on surgery utilization and age of hormone therapy initiation among transgender adults. Methods: We conducted a retrospective review of electronic health record data from a random sample of 201 transgender patients of ages 18–64 years who presented for primary care between July 1, 2010 and June 30, 2015 (inclusive) at an urban community health center in Boston, MA. Fifty percent in our analyses were trans masculine (TM), 50% trans feminine, and 24% reported a genderqueer/nonbinary gender identity. Regression models were fit to assess demographic, gender identity-related, sexual history, and mental health correlates of gender-affirming surgery and of age of hormone therapy initiation. Results: Overall, 95% of patients were prescribed hormones by their primary care provider, and the mean age of initiation of masculinizing or feminizing hormone prescriptions was 31.8 years (SD=11.1). Younger age of initiation of hormone prescriptions was associated with being TM, being a student, identifying as straight/heterosexual, having casual sexual partners, and not having past alcohol use disorder. Approximately one-third (32%) had a documented history of gender-affirming surgery. Factors associated with increased odds of surgery were older age, higher income levels, not identifying as bisexual, and not having a current psychotherapist. Conclusion: This study extends our understanding of prevalence and factors associated with gender-affirming treatments among transgender adults seeking primary care. Findings can inform future interventions to expand delivery of clinical care for transgender patients. PMID:29159310

  9. Factors associated with contraceptive use and initiation of coital activity after childbirth

    Directory of Open Access Journals (Sweden)

    John E Ekabua

    2010-08-01

    Full Text Available John E Ekabua1, Kufre J Ekabua2, Patience Odusolu1, Chritopher U Iklaki1, Thomas U Agan1, Aniekan J Etokidem21Department of Obstetrics and Gynecology, University of Calabar Teaching Hospital, Calabar, Cross River State, Nigeria; 2Department of Community Medicine, University of Calabar Teaching Hospital, Calabar, Cross River State, NigeriaAbstract: The aim of the study is to identify the factors influencing contraceptive use and initiation of sexual intercourse after childbirth. This was a cross-sectional descriptive survey involving 256 consecutive women, who delivered between April and October, 2007, presenting at the Immunization Clinic, University of Calabar Teaching Hospital, Nigeria in April, 2008. Data was obtained using an interviewer-administered structured questionnaire. Women who had antenatal and postnatal counseling were significantly more likely to use contraceptives than those who did not have counseling (odds ratio (OR 0.29; 95% confidence interval (CI 0.14–0.59; P = 0.0002 and OR 0.18; 95% CI 0.08–0.38; P = 0.0000002 respectively. Other variables significantly associated with contraceptive use included education (P = 0.0470 and reproductive goal (P = 0.0303. Linear regression analysis showed direct relationship between caesarean section and episiotomy as modes of delivery, and initiation of coitus (r2 = 0.439 and 0.45 respectively. Concerning residence after childbirth, staying at home and with in-laws showed direct relationship with initiation of coitus (r2 = 0.208 and 10.750 respectively. The number of women abstaining from intercourse showed a decreasing trend with increasing months after childbirth. Initiation of coitus was significantly associated with resumption of menstruation (P < 0.0001 and non-contraceptive use (P = 0.0089. In conclusion, this study shows the need for use of postpartum contraception before fecund women become susceptible to pregnancy.Keywords: postpartum contraception, factors affecting use

  10. FACSY - a three-dimensional kinetic code for nuclear reactors using flux factorization and synthesis approximation

    International Nuclear Information System (INIS)

    Grundmann, U.; Rohde, U.

    1980-06-01

    The kinetics code FACSY solves the time dependent multigroup diffusion equations in three-dimensional geometry. Using the factorization method the neutron flux is split into a product of an amplitude function and a shape function. Generalized point kinetics equations for the amplitude function are obtained weighting the diffusion equation with the stationary flux. The equations of shape functions are solved by the help of synthesis approximation. Both systems of equations are coupled iteratively. The synthesis of shape function in axial direction of the reactor is discontinuous, applying two-dimensional expansion functions in hexagonal geometry. The effect of delayed neutrons is treated by means of their projections on the expansion functions. As an example the time dependent neutron flux distribution is calculated, when a control rod is moved into a reactor. (author)

  11. First measurement of proton's charge form factor at very low Q2 with initial state radiation

    Directory of Open Access Journals (Sweden)

    M. Mihovilovič

    2017-08-01

    Full Text Available We report on a new experimental method based on initial-state radiation (ISR in e–p scattering, which exploits the radiative tail of the elastic peak to study the properties of electromagnetic processes and to extract the proton charge form factor (GEp at extremely small Q2. The ISR technique was implemented in an experiment at the three-spectrometer facility of the Mainz Microtron (MAMI. This led to a precise validation of radiative corrections far away from elastic line and provided first measurements of GEp for 0.001≤Q2≤0.004(GeV/c2.

  12. Factors associated with early weaning at a Child-Friendly Healthcare Initiative Hospitall

    OpenAIRE

    Granville-Garcia, Ana F.; Lins, Ruthinéia D.A.U.; Oliveira, Ana C.B.; Paiva, Saul M.; Sousa, Raulison V.; Martins, Veruska; Silva, Maria S. P.; Ferreira, Jainara M.S.; Menezes, Valdenice A.

    2012-01-01

    PURPOSE: Considering the benefits of breastfeeding on children's health, the aim of the present study was to determine factors associated with early weaning among children at a Child-Friendly Healthcare Initiative (CFHI) children's hospital in the city of Campina Grande, state of Paraíba, Brazil. METHODS: An analytical, cross-sectional study was carried out involving 800 mothers of children between 0 and 24 months of age at the Elpídio de Almeida Health Institute. A semi-structured questionna...

  13. [Inflammatory reaction caused by acupuncture is one of the initial factors of acupuncture effect].

    Science.gov (United States)

    Zhou, Dan; Pan, Ping; Guo, Yi; Guo, Yang-Ming; Wu, Li-Ping

    2009-01-01

    The modern studies indicate that there is a close relationship between mast cells and the acupuncture effect, and acupuncture can activate mast cells to induce a series of vascular reaction and immunological effect. The authors hold that acupuncture is a kind of nociceptive stimulus, which can cause inflammatory reaction in the sites of acupuncture, and then further activate the nerve-endocrine-immune network to cause the cascade amplification of the acupuncture effect. The inflammatory reaction induced by acupuncture is one of the initial factors of acupuncture effect.

  14. Lineage-Determining Transcription Factor TCF-1 Initiates the Epigenetic Identity of T Cells.

    Science.gov (United States)

    Johnson, John L; Georgakilas, Georgios; Petrovic, Jelena; Kurachi, Makoto; Cai, Stanley; Harly, Christelle; Pear, Warren S; Bhandoola, Avinash; Wherry, E John; Vahedi, Golnaz

    2018-02-20

    T cell development is orchestrated by transcription factors that regulate the expression of genes initially buried within inaccessible chromatin, but the transcription factors that establish the regulatory landscape of the T cell lineage remain unknown. Profiling chromatin accessibility at eight stages of T cell development revealed the selective enrichment of TCF-1 at genomic regions that became accessible at the earliest stages of development. TCF-1 was further required for the accessibility of these regulatory elements and at the single-cell level, it dictated a coordinate opening of chromatin in T cells. TCF-1 expression in fibroblasts generated de novo chromatin accessibility even at chromatin regions with repressive marks, inducing the expression of T cell-restricted genes. These results indicate that a mechanism by which TCF-1 controls T cell fate is through its widespread ability to target silent chromatin and establish the epigenetic identity of T cells. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Competition between translation initiation factor eIF5 and its mimic protein 5MP determines non-AUG initiation rate genome-wide.

    Science.gov (United States)

    Tang, Leiming; Morris, Jacob; Wan, Ji; Moore, Chelsea; Fujita, Yoshihiko; Gillaspie, Sarah; Aube, Eric; Nanda, Jagpreet; Marques, Maud; Jangal, Maika; Anderson, Abbey; Cox, Christian; Hiraishi, Hiroyuki; Dong, Leiming; Saito, Hirohide; Singh, Chingakham Ranjit; Witcher, Michael; Topisirovic, Ivan; Qian, Shu-Bing; Asano, Katsura

    2017-11-16

    In the human genome, translation initiation from non-AUG codons plays an important role in various gene regulation programs. However, mechanisms regulating the non-AUG initiation rate remain poorly understood. Here, we show that the non-AUG initiation rate is nearly consistent under a fixed nucleotide context in various human and insect cells. Yet, it ranges from <1% to nearly 100% compared to AUG translation, depending on surrounding sequences, including Kozak, and possibly additional nucleotide contexts. Mechanistically, this range of non-AUG initiation is controlled in part, by the eIF5-mimic protein (5MP). 5MP represses non-AUG translation by competing with eIF5 for the Met-tRNAi-binding factor eIF2. Consistently, eIF5 increases, whereas 5MP decreases translation of NAT1/EIF4G2/DAP5, whose sole start codon is GUG. By modulating eIF5 and 5MP1 expression in combination with ribosome profiling we identified a handful of previously unknown non-AUG initiation sites, some of which serve as the exclusive start codons. If the initiation rate for these codons is low, then an AUG-initiated downstream ORF prevents the generation of shorter, AUG-initiated isoforms. We propose that the homeostasis of the non-AUG translatome is maintained through balanced expression of eIF5 and 5MP. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. Catalytic synthesis of enantiopure mixed diacylglycerols - synthesis of a major M. tuberculosis phospholipid and platelet activating factor

    NARCIS (Netherlands)

    Fodran, Peter; Minnaard, Adriaan J.

    2013-01-01

    An efficient catalytic one-pot synthesis of TBDMS-protected diacylglycerols has been developed, starting from enantiopure glycidol. Subsequent migration-free deprotection leads to stereo- and regiochemically pure diacylglycerols. This novel strategy has been applied to the synthesis of a major

  17. A eukaryotic initiation factor 5C is upregulated during metamorphosis in the cotton bollworm, Helicoverpa armigera.

    Science.gov (United States)

    Dong, Du-Juan; Wang, Jin-Xing; Zhao, Xiao-Fan

    2009-03-08

    The orthologs of eukaryotic initiation factor 5C (eIF5C) are essential to the initiation of protein translation, and their regulation during development is not well known. A cDNA encoding a polypeptide of 419 amino acids containing an N-terminal leucine zipper motif and a C-terminal eIF5C domain was cloned from metamorphic larvae of Helicoverpa armigera. It was subsequently named Ha-eIF5C. Quantitative real-time PCR (QRT-PCR) revealed a high expression of the mRNA of Ha-eIF5C in the head-thorax, integument, midgut, and fat body during metamorphosis. Immunohistochemistry suggested that Ha-eIF5C was distributed into both the cytoplasm and the nucleus in the midgut, fat body and integument. Ha-eIF5C expression was upregulated by 20-hydroxyecdysone (20E). Furthermore, the transcription of Ha-eIF5C was down regulated after silencing of ecdysteroid receptor (EcR) or Ultraspiracle protein (USP) by RNAi. These results suggested that during metamorphosis of the cotton bollworm, Ha-eIF5C was upregulated by 20E through the EcR and USP transcription factors.

  18. A eukaryotic initiation factor 5C is upregulated during metamorphosis in the cotton bollworm, Helicoverpa armigera

    Directory of Open Access Journals (Sweden)

    Zhao Xiao-Fan

    2009-03-01

    Full Text Available Abstract Background The orthologs of eukaryotic initiation factor 5C (eIF5C are essential to the initiation of protein translation, and their regulation during development is not well known. Results A cDNA encoding a polypeptide of 419 amino acids containing an N-terminal leucine zipper motif and a C-terminal eIF5C domain was cloned from metamorphic larvae of Helicoverpa armigera. It was subsequently named Ha-eIF5C. Quantitative real-time PCR (QRT-PCR revealed a high expression of the mRNA of Ha-eIF5C in the head-thorax, integument, midgut, and fat body during metamorphosis. Immunohistochemistry suggested that Ha-eIF5C was distributed into both the cytoplasm and the nucleus in the midgut, fat body and integument. Ha-eIF5C expression was upregulated by 20-hydroxyecdysone (20E. Furthermore, the transcription of Ha-eIF5C was down regulated after silencing of ecdysteroid receptor (EcR or Ultraspiracle protein (USP by RNAi. Conclusion These results suggested that during metamorphosis of the cotton bollworm, Ha-eIF5C was upregulated by 20E through the EcR and USP transcription factors.

  19. Factors associated with breastfeeding initiation time in a baby-friendly hospital in Istanbul.

    Science.gov (United States)

    İnal, Sevil; Aydin, Yasemin; Canbulat, Nejla

    2016-11-01

    To investigate perinatal factors that affect breastfeeding of newborns delivered at a baby-friendly public hospital in Turkey, including the time of the first physical examination by a pediatrician, the first union with their mothers, and the first breastfeeding time after delivery. The research was conducted from May 2nd through June 30th, 2011, in a baby-friendly public hospital in Istanbul. The sample consisted of 194 mothers and their full-term newborns. The data were collected via an observation form developed by the researchers. In analyzing the data, the average, standard deviation, minimum, maximum values, Chi-square, and percentages were used. The results revealed that the first physical examinations of the newborns were performed approximately 53.02±39min (range, 1-180 min) after birth. The newborns were given to their mothers approximately 69.75±41min (range, 3-190 min) after birth. Consequently, the first initiated breastfeeding took place approximately 78.58±44min following birth, and active sucking was initiated after approximately 85.90±54min. A large percentage of the newborns (64.4%) were not examined by a specialist pediatrician within half an hour of birth, and 74.7% were not united with their mothers within the same period. Also, the newborns who initiated breastfeeding within the first half hour had significantly earlier success with active sucking and required significantly less assistance to achieve successful breastfeeding. The newborns in our study met with their mothers late in the birth ward because examinations of the newborns were delayed. The newborns began initial sucking later, and this chain reaction negatively impacted the breastfeeding success of the newborns. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Understanding the factors that make public participation effective in health policy and planning: a realist synthesis.

    Science.gov (United States)

    Pagatpatan, Celso P; Ward, Paul R

    2017-06-23

    Although researchers argue for the importance of involving the public in developing health policy, there has been little focus on central research questions - such as what techniques of public participation work, in what circumstances, and why. This paper presents a realist synthesis which identifies and explains the underlying mechanisms and specific contextual factors that lead to effective public participation in health policy and planning. Peer-reviewed, English language literature was searched, which resulted in 77 articles for review and synthesis. This synthesis uncovered the underlying mechanism of 'political commitment' that generates public participation effectiveness. The other three possible underlying mechanisms, namely: 'partnership synergy', 'inclusiveness' and 'deliberativeness', were found to potentially provide further explanation on public participation effectiveness for health policy and planning. The findings of this review provide evidence that can be useful to health practitioners and decision-makers to actively involve the public when drafting public health policies and programs and, more importantly, guide them in deciding which strategies to best employ for which contexts.

  1. Gene regulation of UDP-galactose synthesis and transport: Potential rate limiting processes in initiation of milk production in humans

    Science.gov (United States)

    Lactose synthesis is believed to be rate-limiting for milk production. However, understanding the molecular events controlling lactose synthesis in humans is still rudimentary. We have utilized our established model of the RNA isolated from breast milk fat globule from 7 healthy exclusively breastfe...

  2. RNA interference-mediated silencing of eukaryotic translation initiation factor 3, subunit B (EIF3B) gene expression inhibits proliferation of colon cancer cells.

    Science.gov (United States)

    Wang, Zheng; Chen, Jinxian; Sun, Jianhua; Cui, Zhe; Wu, Hui

    2012-06-26

    A key factor underlying the control of the cellular growth, size and proliferation involves the regulation of the total protein synthesis. Most often, the initial stages of mRNA translation are rate limiting, which involves a group of eukaryotic translation initiation factors (EIFs). Research advances focused on the inhibition of their expression and activity hold the key to the initiation and progression of tumor and tumor prognosis. We performed RNA interference (RNAi) with the lentivirus vector system to silence the EIF3B gene using the colon cancer cell strain SW1116. The negative control included the normal target cells infected with the negative control virus whereas the knockdown cells included the normal target cells transfected with the RNAi target virus. We tested the inhibition resulting from the decreased expression of EIF3B gene on the proliferation rate of SW1116 cells, including the cell cycle, apoptosis and clonability. Compared with the negative control, the impact of EIF3B gene expression in SW1116 cells on the levels of mRNA and protein in the knockdown group, was significantly inhibited (P cell proliferation rate and clonability were also significantly inhibited (P cells in the G1 phase (P cells.

  3. Factorization and the synthesis of optimal feedback gains for distributed parameter systems

    Science.gov (United States)

    Milman, Mark H.; Scheid, Robert E.

    1990-01-01

    An approach based on Volterra factorization leads to a new methodology for the analysis and synthesis of the optimal feedback gain in the finite-time linear quadratic control problem for distributed parameter systems. The approach circumvents the need for solving and analyzing Riccati equations and provides a more transparent connection between the system dynamics and the optimal gain. The general results are further extended and specialized for the case where the underlying state is characterized by autonomous differential-delay dynamics. Numerical examples are given to illustrate the second-order convergence rate that is derived for an approximation scheme for the optimal feedback gain in the differential-delay problem.

  4. The initial step of silicate versus aluminosilicate formation in zeolite synthesis: a reaction mechanism in water with a tetrapropylammonium template

    KAUST Repository

    Trinh, Thuat T.

    2012-01-01

    The initial step for silicate and aluminosilicate condensation is studied in water in the presence of a realistic tetrapropylammonium template under basic conditions. The model corresponds to the synthesis conditions of ZSM5. The free energy profile for the dimer formation ((OH) 3Si-O-Si-(OH) 2O - or [(OH) 3Al-O-Si-(OH) 3] -) is calculated with ab initio molecular dynamics and thermodynamic integration. The Si-O-Si dimer formation occurs in a two-step manner with an overall free energy barrier of 75 kJ mol -1. The first step is associated with the Si-O bond formation and results in an intermediate with a five-coordinated Si, and the second one concerns the removal of the water molecule. The template is displaced away from the Si centres upon dimer formation, and a shell of water molecules is inserted between the silicate and the template. The main effect of the template is to slow down the backward hydrolysis reaction with respect to the condensation one. The Al-O-Si dimer formation first requires the formation of a metastable precursor state by proton transfer from Si(OH) 4 to Al(OH) 4 - mediated by a solvent molecule. It then proceeds through a single step with an overall barrier of 70 kJ mol -1. The model with water molecules explicitly included is then compared to a simple calculation using an implicit continuum model for the solvent. The results underline the importance of an explicit and dynamical treatment of the water solvent, which plays a key role in assisting the reaction. © the Owner Societies 2012.

  5. Recessive Resistance to Plant Viruses: Potential Resistance Genes Beyond Translation Initiation Factors

    Directory of Open Access Journals (Sweden)

    Masayoshi Hashimoto

    2016-10-01

    Full Text Available The ability of plant viruses to propagate their genomes in host cells depends on many host factors. In the absence of an agrochemical that specifically targets plant viral infection cycles, one of the most effective methods for controlling viral diseases in plants is taking advantage of the host plant’s resistance machinery. Recessive resistance is conferred by a recessive gene mutation that encodes a host factor critical for viral infection. It is a branch of the resistance machinery and, as an inherited characteristic, is very durable. Moreover, recessive resistance may be acquired by a deficiency in a negative regulator of plant defense responses, possibly due to the autoactivation of defense signaling. Eukaryotic translation initiation factor (eIF 4E and eIF4G and their isoforms are the most widely exploited recessive resistance genes in several crop species, and they are effective against a subset of viral species. However, the establishment of efficient, recessive resistance-type antiviral control strategies against a wider range of plant viral diseases requires genetic resources other than eIF4Es. In this review, we focus on recent advances related to antiviral recessive resistance genes evaluated in model plants and several crop species. We also address the roles of next-generation sequencing and genome editing technologies in improving plant genetic resources for recessive resistance-based antiviral breeding in various crop species.

  6. Implementation of oral health initiatives by Australian rural communities: Factors for success.

    Science.gov (United States)

    Taylor, Judy; Carlisle, Karen; Farmer, Jane; Larkins, Sarah; Dickson-Swift, Virginia; Kenny, Amanda

    2018-01-01

    In this paper, we consider factors significant in the success of community participation in the implementation of new oral health services. Our analysis draws on data from the Rural Engaging Communities in Oral Health (Rural ECOH) study (2014-2016). We aimed to assess the Australian relevance of a Scottish community participation framework for health service development; Remote Service Futures. Internationally, community participation in planning of health initiatives is common, but less common in new service implementation. Health managers query the legitimacy of "lay" community members, whether they will persist, and whether they can act as change agents. Our data provide evidence that helps answer these queries. Six communities, located within regions covered by two large rural primary healthcare organisations (Medicare Locals), were selected in two Australian states. Two university-based facilitators worked with a group of local residents (for each community) to monitor implementation of new oral health initiatives designed through participatory processes. Data about implementation were collected through interviews with 28 key stakeholders at the beginning of implementation and 12 months later. Data were coded, themed and analysed abductively. Five themes emerged; the inter-relationship between community motivation to participate with the fortunes of the oral health initiatives, having the "right" people involved, continuing involvement of sponsors and/or significant people, trusting working relationships between participants and perceiving benefits from participation. Findings provide evidence of a role for community participation in implementing new community services if solid partnerships with relevant providers can be negotiated and services are seen to be relevant and useful to the community. © 2017 John Wiley & Sons Ltd.

  7. Factors affecting recruitment into depression trials: Systematic review, meta-synthesis and conceptual framework.

    Science.gov (United States)

    Hughes-Morley, Adwoa; Young, Bridget; Waheed, Waquas; Small, Nicola; Bower, Peter

    2015-02-01

    Depression is common and clinical trials are crucial for evaluating treatments. Difficulties in recruiting participants into depression trials are well-documented, yet no study has examined the factors affecting recruitment. This review aims to identify the factors affecting recruitment into depression trials and to develop a conceptual framework through systematic assessment of published qualitative research. Systematic review and meta-synthesis of published qualitative studies. Meta-synthesis involves a synthesis of themes across a number of qualitative studies to produce findings that are "greater than the sum of the parts". ASSIA, CINAHL, Embase, Medline and PsychInfo were searched up to April 2013. Reference lists of included studies, key publications and relevant reviews were also searched. Quality appraisal adopted the "prompts for appraising qualitative research". 7977 citations were identified, and 15 studies were included. Findings indicate that the decision to enter a depression trial is made by patients and gatekeepers based on the patient׳s health state at the time of being approached to participate; on their attitude towards the research and trial interventions; and on the extent to which patients become engaged with the trial. Our conceptual framework highlights that the decision to participate by both the patient and the gatekeeper involves a judgement between risk and reward. Only English language publications were included in this review. Findings from this review have implications for the design of interventions to improve recruitment into depression trials. Such interventions may aim to diminish the perceived risks and increase the perceived rewards of participation. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  8. Factors affecting the initial literacy development of urban and rural learners in the Iganga district, Uganda

    Directory of Open Access Journals (Sweden)

    Banda, Felix

    2005-12-01

    Full Text Available The initial motivation for the study was data from the Ministry of Education in Uganda that suggests that in terms of academic performance, urban learners continually outperform rural schools at primary and secondary school levels (Ministry of Education 2002. At present all government examinations are written in English. However, the language in education policy in Uganda differentially stipulates the use English as medium of instruction in urban schools and the use of the mother tongue in rural schools (cf. Kyeyune 2004. Other factors which mitigate against rural learners’ successful academic performance are untrained educators, poor infrastructure and school management practices in rural schools, poverty, lack of supportive academic discourse practices, and a general lack of enthusiasm among rural parents (most of whom have very little formal education for their children’s education. Using data from observations of selected urban and rural homes and schools in The Iganga district and field notes in the form of diary entries, the study draws on New Literacy Studies (NLS particularly the notion of literacy as social practice (Street 2001; Gee 2000; Baynham 2000, 2001, to explore the differential effect of urban and rural-based acculturation processes on the initial literacy development of learners. Finally, since 88% of Ugandans live in rural areas (Uganda Bureau of Statistics 2002, the pedagogical implications for primary schools are discussed and suggestions are made on how to establish an inclusive education system.

  9. Factors predicting Behavior Management Problems during Initial Dental Examination in Children Aged 2 to 8 Years.

    Science.gov (United States)

    Sharma, Arun; Kumar, Dipanshu; Anand, Ashish; Mittal, Vipula; Singh, Aparna; Aggarwal, Nidhi

    2017-01-01

    The aim of the present study was to identify the various background variables and its influence on behavior management problems (BMP) in children. The study included 165 children aged 2 to 8 years. During the initial dental visit, an experienced operator obtained each child's background variables from accompanying guardians using a standardized questionnaire. Children's dental behavior was rated by Frankel behavior rating scale. The behavior was then analyzed in relation to the answers of the questionnaire, and a logistic regression model was used to determine the power of the variables, separately or combined, to predict BMP. The logistic regression analysis considering differences in background variables between children with negative or positive behavior. Four variables turned out to be as predictors: Age, the guardian's expectation of the child's behavior at the dental examination, the child's anxiety when meeting unfamiliar people, and the presence and absence of toothache. The present study concluded that by means of simple questionnaire BMP in children may be expected if one of these attributes is found. Information on the origin of dental fear and uncooperative behavior in a child patient prior to treatment process may help the pediatric dentist plan appropriate behavior management and treatment strategy. Sharma A, Kumar D, Anand A, Mittal V, Singh A, Aggarwal N. Factors predicting Behavior Management Problems during Initial Dental Examination in Children Aged 2 to 8 Years. Int J Clin Pediatr Dent 2017;10(1):5-9.

  10. Eukaryotic Initiation Factor 6, an evolutionarily conserved regulator of ribosome biogenesis and protein translation

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Jianjun [Harvard University; Jin, Zhaoqing [ORNL; Yang, Xiaohan [ORNL; Li, Jian-Feng [Harvard University; Chen, Jay [ORNL

    2011-01-01

    We recently identified Receptor for Activated C Kinase 1 (RACK1) as one of the molecular links between abscisic acid (ABA) signaling and its regulation on protein translation. Moreover, we identified Eukaryotic Initiation Factor 6 (eIF6) as an interacting partner of RACK1. Because the interaction between RACK1 and eIF6 in mammalian cells is known to regulate the ribosome assembly step of protein translation initiation, it was hypothesized that the same process of protein translation in Arabidopsis is also regulated by RACK1 and eIF6. In this article, we analyzed the amino acid sequences of eIF6 in different species from different lineages and discovered some intriguing differences in protein phosphorylation sites that may contribute to its action in ribosome assembly and biogenesis. In addition, we discovered that, distinct from non-plant organisms in which eIF6 is encoded by a single gene, all sequenced plant genomes contain two or more copies of eIF6 genes. While one copy of plant eIF6 is expressed ubiquitously and might possess the conserved function in ribosome biogenesis and protein translation, the other copy seems to be only expressed in specific organs and therefore may have gained some new functions. We proposed some important studies that may help us better understand the function of eIF6 in plants.

  11. Transcription Factor Interplay between LEAFY and APETALA1/CAULIFLOWER during Floral Initiation.

    Science.gov (United States)

    Goslin, Kevin; Zheng, Beibei; Serrano-Mislata, Antonio; Rae, Liina; Ryan, Patrick T; Kwaśniewska, Kamila; Thomson, Bennett; Ó'Maoiléidigh, Diarmuid S; Madueño, Francisco; Wellmer, Frank; Graciet, Emmanuelle

    2017-06-01

    The transcription factors LEAFY (LFY) and APETALA1 (AP1), together with the AP1 paralog CAULIFLOWER (CAL), control the onset of flower development in a partially redundant manner. This redundancy is thought to be mediated, at least in part, through the regulation of a shared set of target genes. However, whether these genes are independently or cooperatively regulated by LFY and AP1/CAL is currently unknown. To better understand the regulatory relationship between LFY and AP1/CAL and to obtain deeper insights into the control of floral initiation, we monitored the activity of LFY in the absence of AP1/CAL function. We found that the regulation of several known LFY target genes is unaffected by AP1/CAL perturbation, while others appear to require AP1/CAL activity. Furthermore, we obtained evidence that LFY and AP1/CAL control the expression of some genes in an antagonistic manner. Notably, these include key regulators of floral initiation such as TERMINAL FLOWER1 ( TFL1 ), which had been previously reported to be directly repressed by both LFY and AP1. We show here that TFL1 expression is suppressed by AP1 but promoted by LFY. We further demonstrate that LFY has an inhibitory effect on flower formation in the absence of AP1/CAL activity. We propose that LFY and AP1/CAL act as part of an incoherent feed-forward loop, a network motif where two interconnected pathways or transcription factors act in opposite directions on a target gene, to control the establishment of a stable developmental program for the formation of flowers. © 2017 American Society of Plant Biologists. All Rights Reserved.

  12. Factors Influencing Mothers to Initiate Early Complementary Feeding in Darjeeling, West Bengal

    Directory of Open Access Journals (Sweden)

    Tapas Kumar Sarkar

    2017-10-01

    Full Text Available Introduction: More than half of the infants are started on complementary feed before six months. Perception of Inadequate Milk supply (PIM remains one of the most frequent causes of early institution of complementary feeding. Perception of Inadequate Weight Gain (PIWG, may also influence a mother’s decision to start early complementary feeding which may be a consequence of PIM. Aim: To find the proportion of early complementary feeding and to compare predictive models in identifying mothers who are more likely to initiate early complementary feeds. Materials and Methods: A descriptive epidemiological study with cross-sectional design was carried out for three months between May-July 2013 among 99 mother-child dyads, with children in the 6-24 months age group, residing in Matigara block of West Bengal. Data were collected regarding infant feeding practices and prevalence of early complementary feeding was calculated. Logistic regression was done using SPSS Version 20.0 with the predictor variables classified under three constructs of socio-demography, health system related factors and mothers perceptions; and models were constructed using one, two or all three constructs. Results: The proportion of early complementary feeding was 30.3%. In univariate analysis, none of the variables were found to be statistically significant. However, on multivariate analysis, Model (with all variables was found to be statistically significant. The best Area Under Curve (AUC was found with the inclusion of the socio-demography, health system related factors and mothers’ perception. Conclusion: The perception of the mother regarding adequacy of her milk production and regarding the child’s weight gain are the most important predictors of early initiation of complementary feeding. All counselling activities for the mother should therefore be designed in a way as to address these issues.

  13. Matriptase activation connects tissue factor-dependent coagulation initiation to epithelial proteolysis and signaling.

    Science.gov (United States)

    Le Gall, Sylvain M; Szabo, Roman; Lee, Melody; Kirchhofer, Daniel; Craik, Charles S; Bugge, Thomas H; Camerer, Eric

    2016-06-23

    The coagulation cascade is designed to sense tissue injury by physical separation of the membrane-anchored cofactor tissue factor (TF) from inactive precursors of coagulation proteases circulating in plasma. Once TF on epithelial and other extravascular cells is exposed to plasma, sequential activation of coagulation proteases coordinates hemostasis and contributes to host defense and tissue repair. Membrane-anchored serine proteases (MASPs) play critical roles in the development and homeostasis of epithelial barrier tissues; how MASPs are activated in mature epithelia is unknown. We here report that proteases of the extrinsic pathway of blood coagulation transactivate the MASP matriptase, thus connecting coagulation initiation to epithelial proteolysis and signaling. Exposure of TF-expressing cells to factors (F) VIIa and Xa triggered the conversion of latent pro-matriptase to an active protease, which in turn cleaved the pericellular substrates protease-activated receptor-2 (PAR2) and pro-urokinase. An activation pathway-selective PAR2 mutant resistant to direct cleavage by TF:FVIIa and FXa was activated by these proteases when cells co-expressed pro-matriptase, and matriptase transactivation was necessary for efficient cleavage and activation of wild-type PAR2 by physiological concentrations of TF:FVIIa and FXa. The coagulation initiation complex induced rapid and prolonged enhancement of the barrier function of epithelial monolayers that was dependent on matriptase transactivation and PAR2 signaling. These observations suggest that the coagulation cascade engages matriptase to help coordinate epithelial defense and repair programs after injury or infection, and that matriptase may contribute to TF-driven pathogenesis in cancer and inflammation.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-02-01

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

  15. Evaluation of occupational factors on continuation of breastfeeding and formula initiation in employed mothers.

    Science.gov (United States)

    Ahmadi, Mahshid; Moosavi, Seyyed Mohammad

    2013-09-25

    During recent decades, women have been increasingly involved in social activities. Despite the fact that mothers prefer to breastfeed, their return to work is associated with a reduction in breastfeeding frequency and duration. The present study evaluates the impact of occupational factors on continuation of breastfeeding and formula initiation in employed mothers with infants aged 6-12 months in Bandar-Abbas, Iran in 2010. This is a descriptive-analytic study on employed mothers with infants aged 6-12 months referring to healthcare centers of Bandar-Abbas in 2010. Data were collected through a questionnaire dealing with work-related factors in mothers' workplace. Out of 212 mothers who responded, 52.38% used formula to feed their children, and 27.36% had discontinued breastfeeding. The rate of formula use was significantly higher in mothers who had less than 6 months of maternity leave, those who did not have a suitable nursery or place to milk themselves and preserve the milk in their workplace, those working more than 6 hours per day, and those who could not take a breastfeeding break. It is essential to identify and support breastfeeding employed women. The employers should provide facilities such as nurseries, a suitable physical space for milking, as well as the equipment necessary for milk preservation. Also, such mothers should be granted breastfeeding breaks to feed their child or milk their breasts.

  16. Understanding the factors associated with initiation and adherence of osteoporosis medication in Japan: An analysis of patient perceptions

    Directory of Open Access Journals (Sweden)

    Hajime Orimo

    2017-12-01

    Conclusions: Different factors were found to be associated with initiation and adherence of osteoporosis medication. Patient knowledge of their disease and the perception of barriers were found to be the most influential. Empowering patients with the knowledge to better understand their disease and decreasing the perception of barriers through education initiatives may be effective in improving patient outcomes.

  17. Motivational Factors and Worldview Dimensions Associated with Perceptions of Global Education Initiatives by U.S. College Professors

    Science.gov (United States)

    Jean Francois, Emmanuel

    2010-01-01

    The purpose of this study was to investigate motivational factors and worldview dimensions associated with perceptions of global education initiatives by college professors in the United States. The concept of "perceptions of global education initiatives" is used in this study to refer to attitudes toward institutional support for global…

  18. Averaged strain energy density-based synthesis of crack initiation life in notched steel bars under torsional fatigue

    Directory of Open Access Journals (Sweden)

    Filippo Berto

    2016-10-01

    Full Text Available The torsional fatigue behaviour of circumferentially notched specimens made of austenitic stainless steel, SUS316L, and carbon steel, SGV410, characterized by different notch root radii has been recently investigated by Tanaka. In that contribution, it was observed that the total fatigue life of the austenitic stainless steel increases with increasing stress concentration factor for a given applied nominal shear stress amplitude. By using the electrical potential drop method, Tanaka observed that the crack nucleation life was reduced with increasing stress concentration, on the other hand the crack propagation life increased. The experimental fatigue results, originally expressed in terms of nominal shear stress amplitude, have been reanalysed by means of the local strain energy density (SED averaged over a control volume having radius R0 surrounding the notch tip. To exclude all extrinsic effects acting during the fatigue crack propagation phase, such as sliding contact and/or friction between fracture surfaces, crack initiation life has been considered in the present work. In the original paper, initiation life was defined in correspondence of a 0.1÷0.4-mm-deep crack. The control radius R0 for fatigue strength assessment of notched components, thought of as a material property, has been estimated by imposing the constancy of the averaged SED for both smooth and cracked specimens at NA = 2 million loading cycles

  19. Cap- and initiator tRNA-dependent initiation of TYMV polyprotein synthesis by ribosomes: Evaluation of the Trojan horse model for TYMV RNA translation

    OpenAIRE

    Matsuda, Daiki; Dreher, Theo W.

    2007-01-01

    Turnip yellow mosaic virus (TYMV) RNA directs the translation of two overlapping open reading frames. Competing models have been previously published to explain ribosome access to the downstream polyprotein cistron. The Trojan horse model, based on cell-free experiments, proposes noncanonical cap-independent initiation in which the 3′-terminal tRNA-like structure (TLS) functionally replaces initiator tRNA, and the valine bound to the TLS becomes cis-incorporated into viral protein. The initia...

  20. Cap- and initiator tRNA-dependent initiation of TYMV polyprotein synthesis by ribosomes: evaluation of the Trojan horse model for TYMV RNA translation.

    Science.gov (United States)

    Matsuda, Daiki; Dreher, Theo W

    2007-01-01

    Turnip yellow mosaic virus (TYMV) RNA directs the translation of two overlapping open reading frames. Competing models have been previously published to explain ribosome access to the downstream polyprotein cistron. The Trojan horse model, based on cell-free experiments, proposes noncanonical cap-independent initiation in which the 3'-terminal tRNA-like structure (TLS) functionally replaces initiator tRNA, and the valine bound to the TLS becomes cis-incorporated into viral protein. The initiation coupling model, based on in vivo expression and ribosome toe-printing studies, proposes a variation of canonical leaky scanning. Here, we have re-examined the wheat germ extract experiments that led to the Trojan horse model, incorporating a variety of controls. We report that (1) translation in vitro from the polyprotein AUG of TYMV RNA is unchanged after removal of the 3' TLS but is stimulated by the presence of a 5'-cap; (2) the presence of free cap analog or edeine (which interferes with initiation at the ribosomal P site and its tRNA(i) (Met) involvement) inhibits translation from the polyprotein AUG; (3) the toe-prints of immediately post-initiation ribosomes on TYMV RNA are similar with and without an intact TLS; and (4) significant deacylation of valyl-TYMV RNA in wheat germ extract can complicate the detection of cis-incorporation. These results favor the initiation coupling model.

  1. Gratitude, Hope, Mindfulness and Personal-Growth Initiative: Buffers or Risk Factors for Problem Gambling?

    Science.gov (United States)

    Loo, Jasmine M. Y.; Tsai, Jung-Shun; Raylu, Namrata; Oei, Tian P. S.

    2014-01-01

    The majority of prevention and intervention research in problem gambling (PG) has focused on identifying negative risk factors. However, not all at-risk individuals go on to develop anticipated disorders and many thrive in spite of them. In healthcare settings, PG and other disorders are typically conceptualized from the biomedical perspective that frame disorders as something negative residing within the individual and reduction in negativity is seen as success. Indeed, this problem-focused conceptualization may be adequate in many cases as reducing PG behaviour is undoubtedly an important outcome, but the focus on negativity alone is too narrow to capture the complexity of human behaviour. Hence, this study attempts to bridge the gap in literature by providing an evaluation of the predictive ability of the positive dispositions on problem gambling severity, gambling-related cognitions, and gambling urges. The positive psychological dispositions examined were curiosity, gratitude, hope, personal growth initiative, and mindfulness. Participants consisted of 801 Taiwanese Chinese students and community individuals (Mean age = 25.36 years). Higher levels of gratitude and hope have been found to predict lower PG, gambling-related cognitions, or gambling urges. Meanwhile, higher mindfulness predicted lower PG, but only among Chinese males. However, lower personal growth initiative predicted lower PG, gambling-related cognitions, and gambling urges. These analyses have small to medium effect sizes with significant predictions. Findings of this study have essential implications in understanding and treating Chinese problem gamblers. These positive dispositions should be addressed by mental health professionals in preventative and treatment programs among Chinese individuals. Further implications and suggestions for future research are discussed. PMID:24523854

  2. Gratitude, hope, mindfulness and personal-growth initiative: buffers or risk factors for problem gambling?

    Directory of Open Access Journals (Sweden)

    Jasmine M Y Loo

    Full Text Available The majority of prevention and intervention research in problem gambling (PG has focused on identifying negative risk factors. However, not all at-risk individuals go on to develop anticipated disorders and many thrive in spite of them. In healthcare settings, PG and other disorders are typically conceptualized from the biomedical perspective that frame disorders as something negative residing within the individual and reduction in negativity is seen as success. Indeed, this problem-focused conceptualization may be adequate in many cases as reducing PG behaviour is undoubtedly an important outcome, but the focus on negativity alone is too narrow to capture the complexity of human behaviour. Hence, this study attempts to bridge the gap in literature by providing an evaluation of the predictive ability of the positive dispositions on problem gambling severity, gambling-related cognitions, and gambling urges. The positive psychological dispositions examined were curiosity, gratitude, hope, personal growth initiative, and mindfulness. Participants consisted of 801 Taiwanese Chinese students and community individuals (Mean age = 25.36 years. Higher levels of gratitude and hope have been found to predict lower PG, gambling-related cognitions, or gambling urges. Meanwhile, higher mindfulness predicted lower PG, but only among Chinese males. However, lower personal growth initiative predicted lower PG, gambling-related cognitions, and gambling urges. These analyses have small to medium effect sizes with significant predictions. Findings of this study have essential implications in understanding and treating Chinese problem gamblers. These positive dispositions should be addressed by mental health professionals in preventative and treatment programs among Chinese individuals. Further implications and suggestions for future research are discussed.

  3. Assurance of Myeloid Growth Factor Administration in an Infusion Center: Pilot Quality Improvement Initiative.

    Science.gov (United States)

    Ramirez, Pamela Maree; Peterson, Barry; Holtshopple, Christine; Borja, Kristina; Torres, Vincent; Valdivia-Peppers, Lucille; Harriague, Julio; Joe, Melanie D

    2017-12-01

    Four incident reports involving missed doses of myeloid growth factors (MGFs) triggered the need for an outcome-driven initiative. From March 1, 2015, to February 29, 2016, at University of California Irvine Health Chao Infusion Center, 116 of 3,300 MGF doses were missed (3.52%), including pegfilgrastim, filgrastim, and sargramostim. We hypothesized that with the application of Lean Six Sigma methodology, we would achieve our primary objective of reducing the number of missed MGF doses to < 0.5%. This quality improvement initiative was conducted at Chao Infusion Center as part of a Lean Six Sigma Green Belt Certification Program. Therefore, Lean Six Sigma principles and tools were used throughout each phase of the project. Retrospective and prospective medical record reviews and data analyses were performed to evaluate the extent of the identified problem and impact of the process changes. Improvements included systems applications, practice changes, process modifications, and safety-net procedures. Preintervention, 24 missed doses (20.7%) required patient supportive care measures, resulting in increased hospital costs and decreased quality of care. Postintervention, from June 8, 2016, to August 7, 2016, zero of 489 MGF doses were missed after 2 months of intervention ( P < .001). Chao Infusion Center reduced missed doses from 3.52% to 0%, reaching the goal of < 0.5%. The establishment of simplified and standardized processes with safety checks for error prevention increased quality of care. Lean Six Sigma methodology can be applied by other institutions to produce positive outcomes and implement similar practice changes.

  4. The relationship between transcription initiation RNAs and CCCTC-binding factor (CTCF localization

    Directory of Open Access Journals (Sweden)

    Taft Ryan J

    2011-08-01

    Full Text Available Abstract Background Transcription initiation RNAs (tiRNAs are nuclear localized 18 nucleotide RNAs derived from sequences immediately downstream of RNA polymerase II (RNAPII transcription start sites. Previous reports have shown that tiRNAs are intimately correlated with gene expression, RNA polymerase II binding and behaviors, and epigenetic marks associated with transcription initiation, but not elongation. Results In the present work, we show that tiRNAs are commonly found at genomic CCCTC-binding factor (CTCF binding sites in human and mouse, and that CTCF sites that colocalize with RNAPII are highly enriched for tiRNAs. To directly investigate the relationship between tiRNAs and CTCF we examined tiRNAs originating near the intronic CTCF binding site in the human tumor suppressor gene, p21 (cyclin-dependent kinase inhibitor 1A gene, also known as CDKN1A. Inhibition of CTCF-proximal tiRNAs resulted in increased CTCF localization and increased p21 expression, while overexpression of CTCF-proximal tiRNA mimics decreased CTCF localization and p21 expression. We also found that tiRNA-regulated CTCF binding influences the levels of trimethylated H3K27 at the alternate upstream p21 promoter, and affects the levels of alternate p21 (p21alt transcripts. Extending these studies to another randomly selected locus with conserved CTCF binding we found that depletion of tiRNA alters nucleosome density proximal to sites of tiRNA biogenesis. Conclusions Taken together, these data suggest that tiRNAs modulate local epigenetic structure, which in turn regulates CTCF localization.

  5. Parenteral Nutrition Electrolyte Abnormalities and Associated Factors Before and After Nutrition Support Team Initiation.

    Science.gov (United States)

    Braun, Katie; Utech, Anne; Velez, Maria Eugenia; Walker, Renee

    2018-02-01

    Studied since the 1940s, refeeding syndrome still has no universal definition, thus making comparison of studies difficult. Negative outcomes (eg, metabolic abnormalities) may occur with the use of specialized nutrition, such as parenteral nutrition (PN). Less than half of medical institutions have a nutrition support team (NST) managing PN. Interdisciplinary team management of PN may reduce negative outcomes of PN. The objective of this study was to show the value of the NST by measuring differences in PN variables, especially electrolyte abnormalities (EAs), before and after NST initiation at a large medical center and to identify factors associated with EAs among adult subjects receiving PN. During this retrospective study, computerized medical charts (N = 735) from 2007-2010 were reviewed for electrolyte changes (particularly potassium, magnesium, and phosphorus) the first 3 days following PN initiation in hospitalized adults. Changes in EAs with other variables were compared before and after NST implementation. Equivalent samples sizes were collected to better evaluate the impact of the team. Following the implementation of the NST, fewer EAs were seen in PN patients (53%; χ 2  = 10.906, P = .004); significantly less potassium, phosphorus, and magnesium intravenous piggyback supplementation (88.8% vs 94%; χ 2  = 5.05, P = .026) was used; and mortality within 30 days of PN cessation was significantly less (12.7% vs 10.6%, P = .012). Our study complements existing research, finding that an NST was associated with a decreased occurrence of EAs and mortality in the hospitalized adult receiving PN. © 2016 American Society for Parenteral and Enteral Nutrition.

  6. Local administration of insulin-like growth factor-I (IGF-I) stimulates tendon collagen synthesis in humans

    DEFF Research Database (Denmark)

    Hansen, Mette; Boesen, Anders; Holm, Lars

    2013-01-01

    Collagen is the predominant structural protein in tendons and ligaments, and can be controlled by hormonal changes. In animals, injections of insulin-like growth factor I (IGF-I) has been shown to increase collagen synthesis in tendons and ligaments and to improve structural tissue healing......, but the effect of local IGF-I administration on tendon collagen synthesis in human has not been studied. The purpose of this study was to study whether local injections of IGF-I would have a stimulating effect on tendon collagen synthesis. Twelve healthy nonsmoking men [age 62 ± 1 years (mean ± SEM), BMI 27 ± 1......] participated. Two injections of either human recombinant IGF-I (0.1 mL Increlex©) or saline (control) into each patellar tendon were performed 24-h apart, respectively. Tendon collagen fractional synthesis rate (FSR) was measured by stable isotope technique in the hours after the second injection...

  7. Leishmania eukaryotic initiation factor (LeIF inhibits parasite growth in murine macrophages.

    Directory of Open Access Journals (Sweden)

    Olga Koutsoni

    Full Text Available The leishmaniases constitute neglected global public health problems that require adequate control measures, prophylactic clinical vaccines and effective and non-toxic drug treatments. In this study, we explored the potential of Leishmania infantum eukaryotic initiation factor (LieIF, an exosomal protein, as a novel anti-infective therapeutic molecule. More specifically, we assessed the efficacy of recombinant LieIF, in combination with recombinant IFN-γ, in eliminating intracellular L. donovani parasites in an in vitro macrophage model. J774A.1 macrophages were initially treated with LieIF/IFN-γ prior to in vitro infection with L. donovani stationary phase promastigotes (pre-infection treatment, and resistance to infection was observed 72 h after infection. J774A.1 macrophages were also treated with LieIF/IFN-γ after L. donovani infection (post-infection treatment, and resistance to infection was also observed at both time points tested (19 h and 72 h after infection. To elucidate the LieIF/IFN-γ-induced mechanism(s that mediate the reduction of intracellular parasite growth, we examined the generation of potent microbicidal molecules, such as nitric oxide (NO and reactive oxygen species (ROS, within infected macrophages. Furthermore, macrophages pre-treated with LieIF/IFN-γ showed a clear up-regulation in macrophage inflammatory protein 1α (MIP-1α as well as tumor necrosis factor alpha (TNF-α expression. However, significant different protein levels were not detected. In addition, macrophages pre-treated with LieIF/IFN-γ combined with anti-TNF-α monoclonal antibody produced significantly lower amounts of ROS. These data suggest that during the pre-treatment state, LieIF induces intramacrophage parasite growth inhibition through the production of TNF-α, which induces microbicidal activity by stimulating NO and ROS production. The mechanisms of NO and ROS production when macrophages are treated with LieIF after infection are probably

  8. IgA-binding factor suppresses synthesis of IgA in MOPC-315 plasmacytoma cells

    International Nuclear Information System (INIS)

    Darby, C.; Moore, J.S.; Muller, S.; Aaronsen, D.; Madianos, E.; Hoover, R.G.

    1986-01-01

    T cells with Fc receptors for IgA (T/sup α/ cells) and their products, IgA-binding factors (IgABF), have been implicated in the regulation of IgA expression by B cells. They have previously shown that an IgABF produced by IgA induced normal T cells or constitutively by the Fc/sup α/ R+ T cell lymphoma, BALENTL 8, is capable of suppressing the proliferation and the amount of secreted IgA by MOPC-315 cells. In the present studies, they demonstrate that: (a) suppression of proliferation and secretion requires surface membrane IgA on the target cell, (b) suppression exhibits rapid kinetics with maximal effect occurring by 3-4 hours, (c) suppression is reversible, and (d) suppression of secretion involves selective suppression of IgA synthesis as measured by 3 H-leucine incorporation into immunoprecipitable IgA(non-IgA protein is unaffected). These findings indicate that IgA-isotype-specific effector molecules interact directly with their B cell targets through surface membrane immunoglobulin and cause a down regulation of immunoglobulin synthesis by the target. Current studies are underway to address whether this selective suppression of IgA is mediated at the transcriptional, translational or post-translational level. The use of MOPC-315 tumor cells as targets of T cell produced, isotype-specific, effector molecules should provide a unique model for the further analysis of isotype regulation at the molecular level

  9. The involvement of eukaryotic translation initiation factor 4E in extravillous trophoblast cell function.

    Science.gov (United States)

    Kitroser, E; Pomeranz, M; Epstein Shochet, G; Fishman, A; Drucker, L; Sadeh-Mestechkin, D; Lishner, M; Tartakover-Matalon, S

    2012-09-01

    Extravillous trophoblast cells (EVT) are major players in placental implantation. They differentiate in the villous cell column, invade to the uterus and remodel the uterine spiral arteries. Trophoblast and tumor cells have similar invasion mechanisms, share similar biochemical mediators (e.g. c-myc, MMP9) and growth-factors (e.g. VEGF). The mRNA of these proteins has extremely structured 5-UTR and their translation is highly dependent on eukaryotic-translation-initiation-factor-4E (eIF4E). Cancer cells have elevated eIF4E and are more vulnerable to its silencing than normal cells. We speculated that like cancer, trophoblast function is highly eIF4E dependent. Analyze eIF4E involvement in EVT differentiation and function. EIF4E levels were assessed in first-trimester human placentae and in placental explants before and after EVT differentiation. The effect of eIF4E knockdown (siRNA, ribavirin) on the phenotype of placental explant and EVT cell lines (HTR-8/SVNEO) was evaluated. Tested parameters included eIF4E and its target levels, migration, invasion, cell death, cell cycle and cell count. High eIF4E levels were found in cytotrophoblast and especially EVT cells during their differentiation in the villi, compared to other placental cell types. EIF4E silencing increased cell death and cell cycle arrest in placental explants and HTR-8/SVNEO cells. Although it induced EVT outgrowth in the placental explants, it reduced HTR-8/SVNEO motility, reflecting the importance of using ex vivo models that include an intact placental microenvironment in its original architecture. Our results suggest that eIF4E prevents final EVT differentiation and supports placental cell proliferation and survival. A balance between cell proliferation and differentiation is crucial for placental development and implantation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Innate immune evasion mediated by the Ambystoma tigrinum virus eukaryotic translation initiation factor 2alpha homologue.

    Science.gov (United States)

    Jancovich, James K; Jacobs, Bertram L

    2011-05-01

    Ranaviruses (family Iridoviridae, genus Ranavirus) are large, double-stranded DNA (dsDNA) viruses whose replication is restricted to ectothermic vertebrates. Many highly pathogenic members of the genus Ranavirus encode a homologue of the eukaryotic translation initiation factor 2α (eIF2α). Data in a heterologous vaccinia virus system suggest that the Ambystoma tigrinum virus (ATV) eIF2α homologue (vIF2αH; open reading frame [ORF] 57R) is involved in evading the host innate immune response by degrading the interferon-inducible, dsRNA-activated protein kinase, PKR. To test this hypothesis directly, the ATV vIF2αH gene (ORF 57R) was deleted by homologous recombination, and a selectable marker was inserted in its place. The ATVΔ57R virus has a small plaque phenotype and is 8-fold more sensitive to interferon than wild-type ATV (wtATV). Infection of fish cells with the ATVΔ57R virus leads to eIF2α phosphorylation, in contrast to infection with wtATV, which actively inhibits eIF2α phosphorylation. The inability of ATVΔ57R to prevent phosphorylation of eIF2α correlates with degradation of fish PKZ, an interferon-inducible enzyme that is closely related to mammalian PKR. In addition, salamanders infected with ATVΔ57R displayed an increased time to death compared to that of wtATV-infected salamanders. Therefore, in a biologically relevant system, the ATV vIF2αH gene acts as an innate immune evasion factor, thereby enhancing virus pathogenesis.

  11. Cryptic Protein Priming Sites in Two Different Domains of Duck Hepatitis B Virus Reverse Transcriptase for Initiating DNA Synthesis In Vitro▿

    Science.gov (United States)

    Boregowda, Rajeev K.; Lin, Li; Zhu, Qin; Tian, Fang; Hu, Jianming

    2011-01-01

    Initiation of reverse transcription in hepadnaviruses is accomplished by a unique protein-priming mechanism whereby a specific Y residue in the terminal protein (TP) domain of the viral reverse transcriptase (RT) acts as a primer to initiate DNA synthesis, which is carried out by the RT domain of the same protein. When separate TP and RT domains from the duck hepatitis B virus (DHBV) RT protein were tested in a trans-complementation assay in vitro, the RT domain could also serve, unexpectedly, as a protein primer for DNA synthesis, as could a TP mutant lacking the authentic primer Y (Y96) residue. Priming at these other, so-called cryptic, priming sites in both the RT and TP domains shared the same requirements as those at Y96. A mini RT protein with both the TP and RT domains linked in cis, as well as the full-length RT protein, could also initiate DNA synthesis using cryptic priming sites. The cryptic priming site(s) in TP was found to be S/T, while those in the RT domain were Y and S/T. As with the authentic TP Y96 priming site, the cryptic priming sites in the TP and RT domains could support DNA polymerization subsequent to the initial covalent linkage of the first nucleotide to the priming amino acid residue. These results provide new insights into the complex mechanisms of protein priming in hepadnaviruses, including the selection of the primer residue and the interactions between the TP and RT domains that is essential for protein priming. PMID:21593164

  12. Factors attributing to initiation of tobacco use in adolescent students of Moradabad, (UP India

    Directory of Open Access Journals (Sweden)

    Ravishankar T

    2009-01-01

    Full Text Available Background: Tobacco consumption is a major health menace owing to its widespread use particularly among adolescents. Owing to the presence of impressionable, curious minds, adolescents are highly prone to a number of influences within and outside home, leading them to experiment with tobacco. The addictive nature of tobacco is potent enough to turn these experimental users to addicts. Objectives: To identify the prominent factors leading to initiation of tobacco use among adolescents of Moradabad. Materials and Methods: Two-stage sampling was used to identify 590 adolescents (study population from four senior secondary schools in Moradabad. The response towards tobacco, and its use, was assessed through structured questionnaires. Responses of all study population and association between dependent and explanatory variables were assessed using c2 test (Chi-square test using SPSS package (version 12. Results: The study results show that 17.3% of the adolescents have experimented with tobacco. Curiosity and peer pressure were the main reasons behind trying tobacco. Parental tobacco status, especially place of use (at home or outside, had a significant influence on adolescents experimenting tobacco . Conclusion: Tobacco use by parents is likely to influence adolescents, as they perceive tobacco use as a positive and acceptable behavior, and develop favorable personal beliefs and subjective norms towards tobacco use.

  13. Characterization of the hemin-sensitive eukaryotic initiation factor 2alpha kinase from mouse nonerythroid cells.

    Science.gov (United States)

    Berlanga, J J; Herrero, S; de Haro, C

    1998-11-27

    The heme-regulated eukaryotic initiation factor 2alpha (eIF2alpha) kinase (heme-regulated inhibitor (HRI)) is activated by heme deficiency in reticulocytes and plays an important role in translational control in these cells. Previously, HRI was cloned from rabbit reticulocytes and rat brain, but a heme-regulated eIF2alpha kinase activity has only been purified from erythroid cells. In this study, we report the purification of a heme-sensitive eIF2alpha kinase activity from both mouse liver and NIH 3T3 cell extracts. Furthermore, we have cloned and characterized this mouse liver eIF2alpha kinase (mHRI), which exhibits 83 and 94% identities to rabbit and rat HRIs, respectively. Both the purified enzyme and recombinant mHRI exhibited an autokinase and an eIF2alpha kinase activity, and both activities were inhibited in vitro by hemin. In addition, wild-type mHRI, but not the inactive mHRI-K196R mutant, was autophosphorylated in vivo when it was expressed in 293 cells. Quantitation of mHRI mRNA expression in various mouse tissues by reverse transcription-polymerase chain reaction revealed relatively high levels in liver, kidney, and testis. These results provide strong evidence that mHRI is a ubiquitous eIF2alpha kinase of mammalian cells, suggesting that it could play important roles in the translational regulation of nonerythroid tissues.

  14. Activated alveolar epithelial cells initiate fibrosis through autocrine and paracrine secretion of connective tissue growth factor.

    Science.gov (United States)

    Yang, Jibing; Velikoff, Miranda; Canalis, Ernesto; Horowitz, Jeffrey C; Kim, Kevin K

    2014-04-15

    Fibrogenesis involves a pathological accumulation of activated fibroblasts and extensive matrix remodeling. Profibrotic cytokines, such as TGF-β, stimulate fibroblasts to overexpress fibrotic matrix proteins and induce further expression of profibrotic cytokines, resulting in progressive fibrosis. Connective tissue growth factor (CTGF) is a profibrotic cytokine that is indicative of fibroblast activation. Epithelial cells are abundant in the normal lung, but their contribution to fibrogenesis remains poorly defined. Profibrotic cytokines may activate epithelial cells with protein expression and functions that overlap with the functions of active fibroblasts. We found that alveolar epithelial cells undergoing TGF-β-mediated mesenchymal transition in vitro were also capable of activating lung fibroblasts through production of CTGF. Alveolar epithelial cell expression of CTGF was dramatically reduced by inhibition of Rho signaling. CTGF reporter mice demonstrated increased CTGF promoter activity by lung epithelial cells acutely after bleomycin in vivo. Furthermore, mice with lung epithelial cell-specific deletion of CTGF had an attenuated fibrotic response to bleomycin. These studies provide direct evidence that epithelial cell activation initiates a cycle of fibrogenic effector cell activation during progressive fibrosis. Therapy targeted at epithelial cell production of CTGF offers a novel pathway for abrogating this progressive cycle and limiting tissue fibrosis.

  15. NMR analysis of the interaction of picornaviral proteinases Lb and 2A with their substrate eukaryotic initiation factor 4GII.

    Science.gov (United States)

    Aumayr, Martina; Fedosyuk, Sofiya; Ruzicska, Katharina; Sousa-Blin, Carla; Kontaxis, Georg; Skern, Tim

    2015-12-01

    Messenger RNA is recruited to the eukaryotic ribosome by a complex including the eukaryotic initiation factor (eIF) 4E (the cap-binding protein), the scaffold protein eIF4G and the RNA helicase eIF4A. To shut-off host-cell protein synthesis, eIF4G is cleaved during picornaviral infection by a virally encoded proteinase; the structural basis of this reaction and its stimulation by eIF4E is unclear. We have structurally and biochemically investigated the interaction of purified foot-and-mouth disease virus (FMDV) leader proteinase (Lb(pro)), human rhinovirus 2 (HRV2) 2A proteinase (2A(pro)) and coxsackievirus B4 (CVB4) 2A(pro) with purified eIF4GII, eIF4E and the eIF4GII/eIF4E complex. Using nuclear magnetic resonance (NMR), we completed (13)C/(15) N sequential backbone assignment of human eIF4GII residues 551-745 and examined their binding to murine eIF4E. eIF4GII551-745 is intrinsically unstructured and remains so when bound to eIF4E. NMR and biophysical techniques for determining stoichiometry and binding constants revealed that the papain-like Lb(pro) only forms a stable complex with eIF4GII(551-745) in the presence of eIF4E, with KD values in the low nanomolar range; Lb(pro) contacts both eIF4GII and eIF4E. Furthermore, the unrelated chymotrypsin-like 2A(pro) from HRV2 and CVB4 also build a stable complex with eIF4GII/eIF4E, but with K(D) values in the low micromolar range. The HRV2 enzyme also forms a stable complex with eIF4E; however, none of the proteinases tested complex stably with eIF4GII alone. Thus, these three picornaviral proteinases have independently evolved to establish distinct triangular heterotrimeric protein complexes that may actively target ribosomes involved in mRNA recruitment to ensure efficient host cell shut-off. © 2015 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.

  16. Applications in accessibility of text-to-speech synthesis for South African languages: Initial system integration and user engagement

    CSIR Research Space (South Africa)

    Schlünz, Georg I

    2017-09-01

    Full Text Available with little or no functional speech to speak out loud. Screen readers and accessible e-books allow a print-disabled (visually-impaired, partially-sighted or dyslexic) individual to read text material by listening to audio versions. Text-to-speech synthesis...

  17. Novel Microwave-Assisted Synthesis of Poly(D,L-lactide: The Influence of Monomer/Initiator Molar Ratio on the Product Properties

    Directory of Open Access Journals (Sweden)

    Ljubisa Nikolic

    2010-05-01

    Full Text Available Poly(D,L-lactide synthesis using tin(II 2-ethylhexanoate initiated ring-opening polymerization (ROP takes over 30 hours in bulk at 120 °C. The use of microwave makes the same bulk polymerization process with the same initiator much faster and energy saving, with a reaction time of about 30 minutes at 100 °C. Here, the poly(lactide synthesis was done in a microwave reactor, using frequency of 2.45 GHz and maximal power of 150 W. The reaction temperature was controlled via infra-red system for in-bulk-measuring, and was maintained at 100 °C. Different molar ratios of monomer and initiator, [M]/[I], of 1,000, 5,000 and 10,000 were used. The achieved average molar masses for the obtained polymers (determined by gel permeation chromatography were in the interval from 26,700 to 112,500 g/mol. The polydispersion index was from 2.436 to 3.425. For applicative purposes, the obtained material was purified during the procedure of microsphere preparation. Microspheres were obtained by spraying a fine fog of polymer (D,L-lactide solution in tetrahydrofuran into the water solution of poly(vinyl alcohol with intensive stirring.

  18. Cyclic phosphatidic acid and lysophosphatidic acid induce hyaluronic acid synthesis via CREB transcription factor regulation in human skin fibroblasts.

    Science.gov (United States)

    Maeda-Sano, Katsura; Gotoh, Mari; Morohoshi, Toshiro; Someya, Takao; Murofushi, Hiromu; Murakami-Murofushi, Kimiko

    2014-09-01

    Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator and an analog of the growth factor-like phospholipid lysophosphatidic acid (LPA). cPA has a unique cyclic phosphate ring at the sn-2 and sn-3 positions of its glycerol backbone. We showed before that a metabolically stabilized cPA derivative, 2-carba-cPA, relieved osteoarthritis pathogenesis in vivo and induced hyaluronic acid synthesis in human osteoarthritis synoviocytes in vitro. This study focused on hyaluronic acid synthesis in human fibroblasts, which retain moisture and maintain health in the dermis. We investigated the effects of cPA and LPA on hyaluronic acid synthesis in human fibroblasts (NB1RGB cells). Using particle exclusion and enzyme-linked immunosorbent assays, we found that both cPA and LPA dose-dependently induced hyaluronic acid synthesis. We revealed that the expression of hyaluronan synthase 2 messenger RNA and protein is up-regulated by cPA and LPA treatment time dependently. We then characterized the signaling pathways up-regulating hyaluronic acid synthesis mediated by cPA and LPA in NB1RGB cells. Pharmacological inhibition and reporter gene assays revealed that the activation of the LPA receptor LPAR1, Gi/o protein, phosphatidylinositol-3 kinase (PI3K), extracellular-signal-regulated kinase (ERK), and cyclic adenosine monophosphate response element-binding protein (CREB) but not nuclear factor κB induced hyaluronic acid synthesis by the treatment with cPA and LPA in NB1RGB cells. These results demonstrate for the first time that cPA and LPA induce hyaluronic acid synthesis in human skin fibroblasts mainly through the activation of LPAR1-Gi/o followed by the PI3K, ERK, and CREB signaling pathway. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Quantitative Characterization of Bivalent Probes for a Dual Bromodomain Protein, Transcription Initiation Factor TFIID Subunit 1.

    Science.gov (United States)

    Suh, Junghyun L; Watts, Brian; Stuckey, Jacob I; Norris-Drouin, Jacqueline L; Cholensky, Stephanie H; Dickson, Bradley M; An, Yi; Mathea, Sebastian; Salah, Eidarus; Knapp, Stefan; Khan, Abid; Adams, Alexander T; Strahl, Brian D; Sagum, Cari A; Bedford, Mark T; James, Lindsey I; Kireev, Dmitri B; Frye, Stephen V

    2018-03-28

    Multivalent binding is an efficient means to enhance the affinity and specificity of chemical probes targeting multidomain proteins in order to study their function and role in disease. While the theory of multivalent binding is straightforward, physical and structural characterization of bivalent binding encounters multiple technical difficulties. We present a case study where a combination of experimental techniques and computational simulations was used to comprehensively characterize the binding and structure-affinity relationships for a series of Bromosporine-based bivalent bromodomain ligands with a bivalent protein, Transcription Initiation Factor TFIID subunit 1 (TAF1). Experimental techniques-Isothermal Titration Calorimetry, X-ray Crystallography, Circular Dichroism, Size Exclusion Chromatography-Multi-Angle Light Scattering, and Surface Plasmon Resonance-were used to determine structures, binding affinities, and kinetics of monovalent ligands and bivalent ligands with varying linker lengths. The experimental data for monomeric ligands were fed into explicit computational simulations, in which both ligand and protein species were present in a broad range of concentrations, and in up to a 100 s time regime, to match experimental conditions. These simulations provided accurate estimates for apparent affinities (in good agreement with experimental data), individual dissociation microconstants and other microscopic details for each type of protein-ligand complex. We conclude that the expected efficiency of bivalent ligands in a cellular context is difficult to estimate by a single technique in vitro, due to higher order associations favored at the concentrations used, and other complicating processes. Rather, a combination of structural, biophysical, and computational approaches should be utilized to estimate and characterize multivalent interactions.

  20. Early life factors initiate a 'vicious circle' of affective and gastrointestinal symptoms: A longitudinal study.

    Science.gov (United States)

    Jones, Michael P; Oudenhove, Lukas Van; Koloski, Natasha; Tack, Jan; Talley, Nicholas J

    2013-10-01

    Functional gastrointestinal disorders (FGID) have been shown to be associated with both comorbid mood disorders and traumatic events such as abuse earlier in life. In a longitudinal study, we tested a model that hypothesized: (i) childhood abuse was associated with subsequent mood disorder and pain or interference in life by bowel symptoms both directly and indirectly via neurotic personality; and (ii) an ongoing cycle of mood disorder impacts on bowel symptoms. Subjects from the general population classified as irritable bowel syndrome and/or functional dyspepsia (IBS/FD, n = 207) or free of FGID (n = 100) were prospectively studied every 6 months over 18 months. In addition to bowel symptom interference and abdominal pain, measures of personality (neuroticism), childhood abuse history, depression, and anxiety were obtained. The hypothesized model was tested via Path Modelling. Childhood abuse was found to be directly associated with neuroticism but only indirectly associated with baseline interference and mood disorders (via neuroticism). The data further supported an ongoing cycle of elevations in mood disorders and pain/interference by bowel symptoms. The data supported direct effects of interference at one time point on interference at the subsequent time point in addition to indirect effects of prior anxiety and depression. Repeating the model with pain frequency as the outcome yielded almost identical findings which suggests the findings are generalized across domains of symptoms and quality-of-life. Our data provide support for a model characterized by a 'vicious circle' between mood disorders and FGID symptoms in adulthood, with initial input from early life factors.

  1. Role of eukaryotic translation initiation factor 3a in bleomycin-induced pulmonary fibrosis.

    Science.gov (United States)

    Li, Xian-Wei; Wu, Yue-Han; Li, Xiao-Hui; Li, Dai; Du, Jie; Hu, Chang-Ping; Li, Yuan-Jian

    2015-02-15

    Eukaryotic translation initiation factor 3a (eIF3a) is a multifunctional protein and plays an important role in regulation of cellular function including proliferation and differentiation. In the present study, we tested the function of eIF3a in pulmonary fibrosis. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5mg/kg) in rats. Primary pulmonary fibroblasts were cultured for proliferation investigation by BrdU incorporation method and flow cytometry. The expression/level of eIF3a, TGF-β1, ERK1/2 and α-SMA were analyzed by ELISA, real-time PCR or western blot. Results showed that the expression of eIF3a was obviously increased in lungs of pulmonary fibrosis rats accompanied by up-regulation of α-SMA and collagens. In cultured pulmonary fibroblasts, application of exogenous TGF-β1 induced cell proliferation and differentiation concomitantly with up-regulation of eIF3a expression and ERK1/2 phosphorylation. The effects of TGF-β1-induced proliferation of fibroblasts and up-regulation of α-SMA were abolished by eIF3a siRNA. TGF-β1-induced eIF3a expression was reversed in the presence of PD98059, an inhibitor of ERK1/2. These findings suggest that eIF3a plays an important role in bleomycin-induced pulmonary fibrosis by regulating pulmonary fibroblasts׳ function, and up-regulation of eIF3a induced by TGF-β1 is mediated via the ERK1/2 pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Eukaryotic translation initiation factor 5A2 promotes metabolic reprogramming in hepatocellular carcinoma cells.

    Science.gov (United States)

    Cao, Ting-Ting; Lin, Shu-Hai; Fu, Li; Tang, Zhi; Che, Chi-Ming; Zhang, Li-Yi; Ming, Xiao-Yan; Liu, Teng-Fei; Tang, Xu-Ming; Tan, Bin-Bin; Xiang, Di; Li, Feng; Chan, On-Yee; Xie, Dan; Cai, Zongwei; Guan, Xin-Yuan

    2017-01-01

    Reprogramming of intracellular metabolism is common in liver cancer cells. Understanding the mechanisms of cell metabolic reprogramming may present a new basis for liver cancer treatment. In our previous study, we reported that a novel oncogene eukaryotic translation initiation factor 5A2 (EIF5A2) promotes tumorigenesis under hypoxic condition. Here, we aim to investigate the role of EIF5A2 in cell metabolic reprogramming during hepatocellular carcinoma (HCC) development. In this study, we reported that the messenger RNA (mRNA) level of EIF5A2 was upregulated in 59 of 105 (56.2%) HCC clinical samples (P = 0.015), and EIF5A2 overexpression was significantly associated with shorter survival time of patients with HCC (P = 0.021). Ectopic expression of EIF5A2 in HCC cell lines significantly promoted cell growth and accelerated glucose utilization and lipogenesis rates. The high rates of glucose uptake and lactate secretion conferred by EIF5A2 revealed an abnormal activity of aerobic glycolysis in HCC cells. Several key enzymes involved in glycolysis including glucose transporter type 1 and 2, hexokinase 2, phosphofructokinase liver type, glyceraldehyde 3-phosphate dehydrogenase, pyruvate kinase M2 isoform, phosphoglycerate mutase 1 and lactate dehydrogenase A were upregulated by overexpression of EIF5A2. Moreover, EIF5A2 showed positive correlations with FASN and ACSS2, two key enzymes involved in the fatty acid de novo biosynthetic pathway, at both protein and mRNA levels in HCC. These results indicated that EIF5A2 may regulate fatty acid de novo biosynthesis by increasing the uptake of acetate. In conclusion, our findings demonstrate that EIF5A2 has a critical role in HCC cell metabolic reprogramming and may serve as a prominent novel therapeutic target for liver cancer treatment. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Eukaryotic initiation factor 3C silencing inhibits cell proliferation and promotes apoptosis in human glioma.

    Science.gov (United States)

    Hao, Jinmin; Wang, Zhiming; Wang, Yaowu; Liang, Zhaohui; Zhang, Xin; Zhao, Zongmao; Jiao, Baohua

    2015-06-01

    Eukaryotic initiation factor 3, subunit c (eIF3c), an oncogene overexpressed in human cancers, plays an important role in cell tumorigenesis and proliferation. However, studies assessing its function in gliomas are scarce. The present study evaluated for the first time, the role of eIF3c in gliomas. Immunohistochemistry was carried out to assess eIF3c expression in 95 human glioma samples and normal brain tissues. Then, the eIF3c mRNA levels were detected in tumor and normal brain specimens by quantitative RT-PCR. In addition, eIF3c mRNA levels were assessed in four glioma cell lines (U87, U251, A172 and U373) by semi-quantitative RT-PCR. The RNA interference (RNAi) technology was employed to knock down the eIF3c gene in the U251 cells. Western blot analysis, BrdU assay and flow cytometry were used to measure eIF3c protein levels, cell proliferation, cell apoptosis and cell cycle, respectively. The eIF3c protein was overexpressed in the human glioma specimens. In agreement, the eIF3c mRNA expression levels were significantly higher in the human glioma tissues compared with the normal brain samples (Pcell lines. Silencing the eIF3c gene in the U251 cells by RNAi significantly suppressed cell proliferation (Pcell number (Pcells were significantly increased (P<0.01) after eIF3c knockdown. These findings suggest that eIF3c is overexpressed in human gliomas and essential for their proliferation and survival. Therefore, inhibiting eIF3c expression may constitute an effective therapy for human glioma.

  4. Analysis of risk factors associated with unilateral hearing loss in children who initially passed newborn hearing screening.

    Science.gov (United States)

    Appelbaum, Eric N; Howell, Jessica B; Chapman, Derek; Pandya, Arti; Dodson, Kelley M

    2018-03-01

    To analyze 2007 Joint Committee on Infant Hearing (JCIH) risk factors in children with confirmed unilateral hearing loss (UHL) who initially passed newborn hearing screening. Retrospective record review of 16,108 infants who passed newborn hearing screening but had one or more JCIH risk factors prompting subsequent follow-up through the universal newborn hearing screening (UNHS) program in Virginia from 2010 to 2012. The study was reviewed and qualified as exempt by the Virginia Commonwealth University Institutional Review Board (IRB) and the Virginia Department of Health. Over the 2-year study period, 14896 (4.9% of total births) children passed UNHS but had the presence of one or more JCIH risk factor. Ultimately, we identified 121 babies from this group with confirmed hearing loss (0.7%), with 48 babies (0.2%) showing UHL. The most common risk factors associated with the development of confirmed UHL after passing the initial screen were neonatal indicators, craniofacial anomalies, family history, and stigmata of syndrome associated with hearing loss. Neonatal indicators and craniofacial anomalies were the categories most often found in children with confirmed unilateral hearing loss who initially passed their newborn hearing screen. While neonatal indicators were also the most common associated risk factor in all hearing loss, craniofacial abnormalities are relatively more common in children with UHL who initially passed newborn hearing screening. Further studies assessing the etiology underlying the hearing loss and risk factor associations are warranted. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Regulation and kinetics of platelet-activating factor and leukotriene C-4 synthesis by activated human basophils

    NARCIS (Netherlands)

    Lie, W. J.; Homburg, C. H. E.; Kuijpers, T. W.; Knol, E. F.; Mul, F. P. J.; Roos, D.; Tool, A. T. J.

    2003-01-01

    Background Allergic disease is the result of an interplay of many different cell types, including basophils and mast cells, in combination with various inflammatory lipid mediators, such as platelet-activating factor (PAF) and leukotrienes (LT). LTC4 synthesis by human basophils has been studied

  6. Insulin-like Growth Factor 1 Analogs Clicked in the C Domain: Chemical Synthesis and Biological Activities

    Czech Academy of Sciences Publication Activity Database

    Macháčková, Kateřina; Collinsová, Michaela; Chrudinová, Martina; Selicharová, Irena; Pícha, Jan; Buděšínský, Miloš; Vaněk, Václav; Žáková, Lenka; Brzozowski, A. M.; Jiráček, Jiří

    2017-01-01

    Roč. 60, č. 24 (2017), s. 10105-10117 ISSN 0022-2623 Institutional support: RVO:61388963 Keywords : IGF-1 * receptor * synthesis * triazole Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 6.259, year: 2016 http://pubs.acs.org/doi/full/10.1021/acs.jmedchem.7b01331

  7. KO t Bu-Initiated Aryl C–H Iodination: A Powerful Tool for the Synthesis of High Electron Affinity Compounds

    KAUST Repository

    Shi, Qinqin

    2016-03-21

    An efficient iodination reaction of electron-deficient heterocycles is described. The reaction utilizes KOtBu as an initiator and likely proceeds by a radical anion propagation mechanism. This new methodology is particularly effective for functionalization of building blocks for electron transport materials. Its utility is demonstrated with the synthesis of a new perylenediimide-thiazole non-fullerene acceptor capable of delivering a power conversion efficiency of 4.5% in a bulk-heterojunction organic solar cell. © 2016 American Chemical Society.

  8. Crystal structure of the catalytic domain of the initiation factor 2B epsilon subunit from saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Boesen, Thomas; Pavitt, Graham D.; Andersen, Gregers Rom

    residues in the motifs form a surface exposed acidic patch which might interact with the lysine boxes of initiation factor 2 β. Interestingly, tryptophan 699 was found to be solvent exposed and involved in crystal packing. This residue could possibly be important for the specific interaction......Crystal Structure of Catalytic Domain of the Initiation Factor 2B Epsilon Subunit from Saccharomyces cerevisiae by Thomas Boesen1, Graham Pavitt2, and Gregers Rom Andersen1* 1Department of Molecular Biology, University of Aarhus, Gustav Wieds Vej 10C, DK-8000 Århus C, Denmark 2Department...... of Biomolecular Sciences, UMIST, PO Box 88, Manchester, M60 1QD UK *To whom correspondence should be addressed: grand@imsb.au.dk, Tel: (+45) 8942 5024. Fax: (+45) 8612 3178 Abstract The crystal structure of the C-terminal catalytic domain of the initiation factor 2B epsilon subunit, residues 544-704, from...

  9. PROBABILISTIC PROPERTIES OF THE INITIAL VALUES OF WEIGHTING FACTORS IN SYNCHRONIZED ARTIFICIAL NEURAL

    Directory of Open Access Journals (Sweden)

    V. F. Golikov

    2013-01-01

    Full Text Available One of the most efficient ways for identical binary se quences generation is using methods of neural cryptography. The initial weight vestors values influence on speed of synchronization is analized. Equal probability of initial weight vestors motion directions is great advantage. On this base authors suppose new line of research conserned with improvement of network architecture and correction algorithm.

  10. Pulling the Trigger or Not: Factors Affecting Behavior of Initiating a Position in Derivatives Markets

    NARCIS (Netherlands)

    Pennings, J.M.E.

    2002-01-01

    The behavior of managers in initiating a derivatives market position brings to the surface an interesting phenomenon: sometimes managers initiate a position in derivatives markets (i.e., futures and options markets) and sometimes they do not, even though the price volatility of the underlying asset

  11. A tale of two pregnancies: A Critical Interpretive Synthesis of women's perceptions about delayed initiation of antenatal care.

    Science.gov (United States)

    Haddrill, Rosalind; Jones, Georgina L; Anumba, Dilly; Mitchell, Caroline

    2017-10-14

    Delayed access to antenatal care in high income countries is associated with poor maternal, fetal and neonatal outcomes. The aim was to synthesise the diverse body of evidence around women's views of early antenatal care and barriers to attendance in such countries. Critical Interpretive Synthesis integrates the process of systematic review with the qualitative methods of meta-ethnography and grounded theory, with a focus on theory generation to inform policy, practice and future research. Database searches were conducted, supplemented with reference and citation tracking and website searching between February 2014 and April 2016. Qualitative data analysis methods were used to extract and summarise the key themes from each study. A taxonomy of constructs was created, with the synthesis developed to thread these together. Fifty-four papers were synthesised, including qualitative, quantitative, mixed method and systematic review, published between 1987 and 2016. Seventeen constructs around the core concept of 'acceptance of personal and public pregnancies' were produced. Acceptance of the 'personal' pregnancy considers the contribution of mindset in the recognition and acceptance of pregnancy, influenced by knowledge of pregnancy symptoms, pregnancy planning and desire. Acceptance of the 'public' pregnancy considers women's assessment of the social consequences of pregnancy, and the relevance and priority of antenatal care. Critical Interpretive Synthesis offers a systematic yet creative approach to the synthesis of diverse evidence. The findings offer new perspectives on women's perceptions of early pregnancy and attendance for care, which may be used to facilitate timely antenatal provision for all pregnant women. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  12. How Hibernation Factors RMF, HPF, and YfiA Turn Off Protein Synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Polikanov, Yury S.; Blaha, Gregor M.; Steitz, Thomas A. (Yale)

    2013-04-08

    Eubacteria inactivate their ribosomes as 100S dimers or 70S monomers upon entry into stationary phase. In Escherichia coli, 100S dimer formation is mediated by ribosome modulation factor (RMF) and hibernation promoting factor (HPF), or alternatively, the YfiA protein inactivates ribosomes as 70S monomers. Here, we present high-resolution crystal structures of the Thermus thermophilus 70S ribosome in complex with each of these stationary-phase factors. The binding site of RMF overlaps with that of the messenger RNA (mRNA) Shine-Dalgarno sequence, which prevents the interaction between the mRNA and the 16S ribosomal RNA. The nearly identical binding sites of HPF and YfiA overlap with those of the mRNA, transfer RNA, and initiation factors, which prevents translation initiation. The binding of RMF and HPF, but not YfiA, to the ribosome induces a conformational change of the 30S head domain that promotes 100S dimer formation.

  13. [Effect of growth factors and some microelements on biosurfactant synthesis of Acinetobacter calcoaceticus IMV B-7241].

    Science.gov (United States)

    Pirog, T P; Shevchuk, T A; Mashchenko, O Iu; Parfeniuk, S A; Iutinskaia, G A

    2013-01-01

    The effect of yeast autolysate and microelements on synthesis of surface-active substances (SAS, biosurfactants) was investigated under cultivation of Acinetobacter calcoaceticus IMV B-7241 on various carbon substrates (n-hexadecane, ethanol, glycerol). The authors have shown a possibility to substitute the yeast autolysate and microelement mixture in the composition of ethanol- and n-hexadecane-containing media by copper sulfate (0.16 micromol/l) and iron sulfate (3.6 micromol/l), and in the medium with glycerol by 0.21 mmol/l of KCl, 38 micromol/l of zinc sulfate and 0.16 micromol/l of copper sulfate. Under such conditions of cultivation of the strain IMV B-7241 the SAS concentration exceeded that on the initial media, which contained the yeast autolysate and microelements, 1.2-1.6 times. The authors have also established the activating effect of low (0.01 mM) concentrations of Fe2+ on activity of the enzymes of biosynthesis of surface-active amino- (NADP-dependent glutamate dehydrogenase) and glycolipids (phosphoenolpyruvate(PhEP)-synthetase, PhEP-carboxykinase), as well as of anaplerotic reaction(PhEP-carboxylase). A necessity to introduce zinc cations into glycerol-containing medium is determined by their stimulating effect on activity of 4-dinitroso-N,N-dimethylaniline-dependent alcohol dehydrogenase--one of the enzymes of this substrate catabolism in A. calcoaceticus IMV B-7241.

  14. Effects of hepatocyte growth factor on glutathione synthesis, growth, and apoptosis is cell density-dependent

    International Nuclear Information System (INIS)

    Yang Heping; Magilnick, Nathaniel; Xia Meng; Lu, Shelly C.

    2008-01-01

    Hepatocyte growth factor (HGF) is a potent hepatocyte mitogen that exerts opposing effects depending on cell density. Glutathione (GSH) is the main non-protein thiol in mammalian cells that modulates growth and apoptosis. We previously showed that GSH level is inversely related to cell density of hepatocytes and is positively related to growth. Our current work examined whether HGF can modulate GSH synthesis in a cell density-dependent manner and how GSH in turn influence HGF's effects. We found HGF treatment of H4IIE cells increased cell GSH levels only under subconfluent density. The increase in cell GSH under low density was due to increased transcription of GSH synthetic enzymes. This correlated with increased protein levels and nuclear binding activities of c-Jun, c-Fos, p65, p50, Nrf1 and Nrf2 to the promoter region of these genes. HGF acts as a mitogen in H4IIE cells under low cell density and protects against tumor necrosis factor α (TNFα)-induced apoptosis by limiting JNK activation. However, HGF is pro-apoptotic under high cell density and exacerbates TNFα-induced apoptosis by potentiating JNK activation. The increase in cell GSH under low cell density allows HGF to exert its full mitogenic effect but is not necessary for its anti-apoptotic effect

  15. The translation initiation factor eIF4E regulates the sex-specific expression of the master switch gene Sxl in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Patricia L Graham

    2011-07-01

    Full Text Available In female fruit flies, Sex-lethal (Sxl turns off the X chromosome dosage compensation system by a mechanism involving a combination of alternative splicing and translational repression of the male specific lethal-2 (msl-2 mRNA. A genetic screen identified the translation initiation factor eif4e as a gene that acts together with Sxl to repress expression of the Msl-2 protein. However, eif4e is not required for Sxl mediated repression of msl-2 mRNA translation. Instead, eif4e functions as a co-factor in Sxl-dependent female-specific alternative splicing of msl-2 and also Sxl pre-mRNAs. Like other factors required for Sxl regulation of splicing, eif4e shows maternal-effect female-lethal interactions with Sxl. This female lethality can be enhanced by mutations in other co-factors that promote female-specific splicing and is caused by a failure to properly activate the Sxl-positive autoregulatory feedback loop in early embryos. In this feedback loop Sxl proteins promote their own synthesis by directing the female-specific alternative splicing of Sxl-Pm pre-mRNAs. Analysis of pre-mRNA splicing when eif4e activity is compromised demonstrates that Sxl-dependent female-specific splicing of both Sxl-Pm and msl-2 pre-mRNAs requires eif4e activity. Consistent with a direct involvement in Sxl-dependent alternative splicing, eIF4E is associated with unspliced Sxl-Pm pre-mRNAs and is found in complexes that contain early acting splicing factors--the U1/U2 snRNP protein Sans-fils (Snf, the U1 snRNP protein U1-70k, U2AF38, U2AF50, and the Wilms' Tumor 1 Associated Protein Fl(2d--that have been directly implicated in Sxl splicing regulation.

  16. Protective and risk factors of early sexual initiation in youth subcultures

    NARCIS (Netherlands)

    Bobakova, Daniela; Geckova, Andrea Madarasova; Klein, Daniel; van Dijk, Jitse P; Reijneveld, Sijmen A

    Objectives To assess the association between subculture affiliation (Hip-hop, Technoscene, Metal, Punk, Skinheads) and early sexual initiation, and whether gender, family affluence, peer influence, lack of parental bonding and lack of parental monitoring explain this association. Methods We

  17. Unravelling the influence of smoking initiation and cessation on premature mortality using a common latent factor model

    OpenAIRE

    Silvia Balia; Andrew M. Jones

    2007-01-01

    Duration models for lifespan and smoking, that focus on the socio-economic gradient in smoking durations and length of life, are estimated controlling for individual-specific unobservable heterogeneity by means of a latent factor model. The latent factor influences the risk of starting and quitting smoking as well as the hazard of mortality. Frailty could in°uence smoking behaviour through two mechanisms: the effect of life expectancy on initiation of smok- ing and the impact of adverse healt...

  18. What Factors are Associated with Consumer Initiation of Shared Decision Making in Mental Health Visits?

    OpenAIRE

    Matthias, Marianne S.; Fukui, Sadaaki; Salyers, Michelle P.

    2017-01-01

    Understanding consumer initiation of shared decision making (SDM) is critical to improving SDM in mental health consultations, particularly because providers do not always invite consumer participation in treatment decisions. This study examined the association between consumer initiation of nine elements of SDM as measured by the SDM scale, and measures of consumer illness self-management and the consumer-provider relationship. In 63 mental health visits, three SDM elements were associated w...

  19. Synthesis

    International Nuclear Information System (INIS)

    Voinis, Sylvie; Lalieux, Philippe; Thury, Marc; Horseman, Steve

    2001-01-01

    -stones, and shales. The purpose of these proceedings is to provide on the one hand a brief summary of the technical presentations and a record of the main conclusions and outcomes and, on the other hand, a compilation of the presentations' abstracts. very informative presentations provided an overview of the spectrum of the topic; such multidisciplinary overview was - to the knowledge of the Clay Club members - not available before the session; they demonstrated the necessity to consider self-healing in all types of argillaceous media considered as potential host formation; they illustrated the need to reconcile the geomechanical and the geochemical approaches vis-a-vis the self-healing. The discussions focused initially on the clarification of the two phrases 'self-healing' and 'self-sealing'

  20. Influence factor on automated synthesis yield of 3'-deoxy-3'-[18F] fluorothymidine

    International Nuclear Information System (INIS)

    Zhang Jinming; Tian Jiahe; Liu Changbin; Liu Jian; Luo Zhigang

    2009-01-01

    3'-deoxy-3'-[ 18 F] fluorothymidine ( 18 F-FLT) was prepared from N-BOC precursor to improve the synthesis yield, chemical purity and radiochemical purity of 18 F-FLT by home-made automated synthesis module. The results showed that residual water in synthesis system and the amount of precursor could affect the synthesis yield dramatically. The more the amount of precursor, the higher the synthesis yield of N-BOC. The residual water can decrease the synthesis yield. In the presence of excess base, the precursor was consumed by elimination before substitution was completed. The precursor to base was optimal in 1 to 1. The balance of semi-preparatiove HPLC Column can affect purified the final 18 F-FLT product. The chemical purity of 18 F-FLT could be decreased with 8% EtOH as mobile phase in semi-preparatiove HPLC. The high chemical purity, radiochemical purity and synthesis yield could be obtained by optimized the parameter of synthesis with home-made automated synthesis module. (authors)

  1. Teacher Involvement as a Protective Factor from the Association between Race-Based Bullying and Smoking Initiation

    Science.gov (United States)

    Earnshaw, Valerie A.; Rosenthal, Lisa; Carroll-Scott, Amy; Peters, Susan M.; McCaslin, Catherine; Ickovics, Jeannette R.

    2014-01-01

    Experiencing bullying as a victim is associated with negative health and health behavior outcomes, including substance use, among adolescents. However, understandings of protective factorsfactors that enhance adolescents’ resilience to the negative consequences of bullying – remain limited. The current study investigates whether teacher involvement protects adolescent students from the association between being bullied due to race and smoking initiation. Students were recruited from 12 Kindergarten through 8th grade schools in an urban school district in the Northeast United States. The analytic sample included 769 students who responded to surveys in 5th or 6th grade (2009), and two years later in 7th or 8th grade (2011). Students primarily identified as Latino and/or Black, and 90% were eligible for free or reduced lunch. Fifty-four (7%) students initiated smoking between survey time points. Among students reporting lower teacher involvement, race-based bullying was associated with higher likelihood of smoking initiation (OR = 1.69, p = .03). In contrast, among students reporting higher teacher involvement, racebased bullying was not associated with higher likelihood of smoking initiation (OR = 0.95, p = .81). Results suggest that teacher involvement may protect students from the association between race-based bullying and smoking initiation. Enhancing teacher involvement among students experiencing race-based bullying in schools may limit smoking initiation. PMID:24955021

  2. Characterization of the domains of E. coli initiation factor IF2 responsible for recognition of the ribosome

    DEFF Research Database (Denmark)

    Manuel Palacios Moreno, Juan; Andersen, Lars Dyrskjøt; Egebjerg Kristensen, Janni

    1999-01-01

    We have studied the interactions between the ribosome and the domains of Escherichia coli translation initiation factor 2, using an in vitro ribosomal binding assay with wild-type forms, N- and C-terminal truncated forms of IF2 as well as isolated structural domains. A deletion mutant of the fact...

  3. Synthesis, characterization and initial evaluation of 5-nitro-1-(trifluoromethyl-3H-1λ3,2-benziodaoxol-3-one

    Directory of Open Access Journals (Sweden)

    Nico Santschi

    2014-01-01

    Full Text Available The synthesis of 5-nitro-1-(trifluoromethyl-3H-1λ3,2-benziodaoxol-3-one (3, a hypervalent-iodine-based electrophilic trifluoromethylating reagent, is described. Whereas considerations based on cyclic voltammetry and X-ray structural properties would predict an inferior reactivity when compared to the non-nitrated derivative 2, 19F NMR kinetic studies showed that this new derivative is almost one order of magnitude more reactive. Furthermore, differential scanning calorimetry measurements indicated that, in addition, it is also safer to handle.

  4. Protective and risk factors of early sexual initiation in youth subcultures.

    Science.gov (United States)

    Bobakova, Daniela; Geckova, Andrea Madarasova; Klein, Daniel; van Dijk, Jitse P; Reijneveld, Sijmen A

    2013-08-01

    To assess the association between subculture affiliation (Hip-hop, Techno-scene, Metal, Punk, Skinheads) and early sexual initiation, and whether gender, family affluence, peer influence, lack of parental bonding and lack of parental monitoring explain this association. We collected data on 15-year-old primary school pupils who participated in the Health Behaviour in School-aged Children 2009/2010 study. The association of subculture affiliation with early sexual initiation was adjusted for gender, family affluence, peer influence, lack of parental bonding and lack of parental monitoring in five consecutive models using logistic regression. Nearly 50% of the adolescents had a subculture affiliation. These youths were significantly more likely than other adolescents to have had sexual intercourse. Peer influence explained 49% of this association. Adding lack of parental bonding and lack of parental monitoring into the model weakened the association of subculture affiliation with early sexual initiation (20%), but this association remained statistically significant. Youth subculture affiliation is strongly correlated with early sexual initiation. This association is mediated for a large part by peer influence and defective parental monitoring and bonding. Health promotion regarding early sexual initiation should therefore in particular target adolescents under strong influence of peers and with weak parental relationships.

  5. Preoperative short hookwire placement for small pulmonary lesions: evaluation of technical success and risk factors for initial placement failure.

    Science.gov (United States)

    Iguchi, Toshihiro; Hiraki, Takao; Matsui, Yusuke; Fujiwara, Hiroyasu; Masaoka, Yoshihisa; Tanaka, Takashi; Sato, Takuya; Gobara, Hideo; Toyooka, Shinichi; Kanazawa, Susumu

    2018-05-01

    To retrospectively evaluate the technical success of computed tomography fluoroscopy-guided short hookwire placement before video-assisted thoracoscopic surgery and to identify the risk factors for initial placement failure. In total, 401 short hookwire placements for 401 lesions (mean diameter 9.3 mm) were reviewed. Technical success was defined as correct positioning of the hookwire. Possible risk factors for initial placement failure (i.e., requirement for placement of an additional hookwire or to abort the attempt) were evaluated using logistic regression analysis for all procedures, and for procedures performed via the conventional route separately. Of the 401 initial placements, 383 were successful and 18 failed. Short hookwires were finally placed for 399 of 401 lesions (99.5%). Univariate logistic regression analyses revealed that in all 401 procedures only the transfissural approach was a significant independent predictor of initial placement failure (odds ratio, OR, 15.326; 95% confidence interval, CI, 5.429-43.267; p failure (OR 0.793, 95% CI 0.631-0.996; p = 0.046). The technical success of preoperative short hookwire placement was extremely high. The transfissural approach was a predictor initial placement failure for all procedures and small lesion size was a predictor of initial placement failure for procedures performed via the conventional route. • Technical success of preoperative short hookwire placement was extremely high. • The transfissural approach was a significant independent predictor of initial placement failure for all procedures. • Small lesion size was a significant independent predictor of initial placement failure for procedures performed via the conventional route.

  6. Quercetin suppresses hypoxia-induced accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) through inhibiting protein synthesis.

    Science.gov (United States)

    Lee, Dae-Hee; Lee, Yong J

    2008-10-01

    Quercetin, a ubiquitous bioactive plant flavonoid, has been shown to inhibit the proliferation of cancer cells and induce the accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) in normoxia. In this study, under hypoxic conditions (1% O(2)), we examined the effect of quercetin on the intracellular level of HIF-1alpha and extracellular level of vascular endothelial growth factor (VEGF) in a variety of human cancer cell lines. Surprisingly, we observed that quercetin suppressed the HIF-1alpha accumulation during hypoxia in human prostate cancer LNCaP, colon cancer CX-1, and breast cancer SkBr3 cells. Quercetin treatment also significantly reduced hypoxia-induced secretion of VEGF. Suppression of HIF-1alpha accumulation during treatment with quercetin in hypoxia was not prevented by treatment with 26S proteasome inhibitor MG132 or PI3K inhibitor LY294002. Interestingly, hypoxia (1% O(2)) in the presence of 100 microM quercetin inhibited protein synthesis by 94% during incubation for 8 h. Significant quercetin concentration-dependent inhibition of protein synthesis and suppression of HIF-1alpha accumulation were observed under hypoxic conditions. Treatment with 100 microM cycloheximide, a protein synthesis inhibitor, replicated the effect of quercetin by inhibiting HIF-1alpha accumulation during hypoxia. These results suggest that suppression of HIF-1alpha accumulation during treatment with quercetin under hypoxic conditions is due to inhibition of protein synthesis. (c) 2008 Wiley-Liss, Inc.

  7. Volunteering within Initial Teacher Education: Factors That Boost and Block Participation

    Science.gov (United States)

    Forster, Daniella J.; Archer, Jennifer; Tajin, Rukhsana T.

    2015-01-01

    Voluntary professional experience can be a powerful way for initial teacher education (ITE) students to develop an understanding of schools and their communities. Do ITE students make use of these opportunities? There is little Australian research that explores genuine volunteering that does not "require" students to engage with the…

  8. Critical discussion of social-cognitive factors in smoking initiation among adolescents

    DEFF Research Database (Denmark)

    Bidstrup, Pernille Envold; Tjørnhøj-Thomsen, Tine; Mortensen, Erik Lykke

    2011-01-01

    , social influence, self-efficacy' (ASE) model. Methods. The examination draws on the results of a qualitative follow-up study of smoking initiation based on semi-structured interviews and observations of 12 adolescents in two Danish school classes, grades 7 and 8. The qualitative study was conducted...

  9. Age at sexual initiation and factors associated with it among youths ...

    African Journals Online (AJOL)

    Bernt Lindtjorn

    Early sexual debut increases young peoples' risk for infection with HIV and other STIs. Youth who begin early sexual activity are more likely to have high-risk sex ... Age at Sexual initiation and its determinants among youths in north east Ethiopia 155. Ethiop. J. Health Dev. 2009;23(2) active females carry the greatest risk of ...

  10. The Perfect Match: Factors That Characterize the AACSB International Initial Accreditation Host School and Mentor Relationship

    Science.gov (United States)

    Solomon, Norman A.; Scherer, Robert F.; Oliveti, Joseph J.; Mochel, Lucienne; Bryant, Michael

    2017-01-01

    Initial Association to Advance Collegiate Schools of Business International accreditation involves a process of pairing mentor and host schools to provide guidance and feedback on the congruence of the host school with the accreditation standards. The mentor serves as the primary resource for assisting the host school in identifying gaps with the…

  11. Teachers' Initial and Sustained Use of an Instructional Assistive Technology Tool: Exploring the Mitigating Factors

    Science.gov (United States)

    Bouck, Emily C.; Flanagan, Sara; Heutsche, Anne; Okolo, Cynthia M.; Englert, Carol Sue

    2011-01-01

    This qualitative research project explored factors that mitigated teachers implementing an instructional assistive technology and factors that mitigated its sustained use. Specifically, it explored these issues in relation to a social studies based instructional assistive technology (Virtual History Museum [VHM]), which was originally implemented…

  12. The Ecosystem Factor in Supporting Wiki Initiative for Knowledge Sharing in Malaysian Public Organisation

    Science.gov (United States)

    Khuzaimah, Khairil Hizar Md; Affandi, Haryanti Mohd; Hassan, Fadzil

    2015-01-01

    The purpose of this paper is to highlight the significance of considering the organizational ecosystem in implementing wikis for knowledge sharing.The findings suggest that a prerequisite of an effective wiki is the appreciation of the factors that make up the organizational ecosystem; technical and organizational factors are variable elements of…

  13. Functional and Biochemical Characterization of Human Eukaryotic Translation Initiation Factor 3 in Living Cells

    Czech Academy of Sciences Publication Activity Database

    Wagner, Susan; Herrmannová, Anna; Malík, Radek; Peclinovská, L.; Valášek, Leoš Shivaya

    2014-01-01

    Roč. 34, č. 16 (2014), s. 3041-3052 ISSN 0270-7306 R&D Projects: GA ČR GAP305/10/0335 Institutional support: RVO:61388971 ; RVO:68378050 Keywords : MESSENGER-RNA RECRUITMENT * FACTOR EIF3 * IN-VIVO Subject RIV: CE - Biochemistry Impact factor: 4.777, year: 2014

  14. Translation initiation factor elF3 promotes programmed stop codon readthrough

    Czech Academy of Sciences Publication Activity Database

    Beznosková, Petra; Wagner, Susan; Jansen, Myrte Esmeralda; von der Haar, T.; Valášek, Leoš

    2015-01-01

    Roč. 43, č. 10 (2015), s. 5099-5111 ISSN 0305-1048 R&D Projects: GA ČR(CZ) GA14-05394S Institutional support: RVO:61388971 Keywords : EUKARYOTIC RELEASE FACTOR-1 * RNA RECOGNITION MOTIF * TICK FEVER VIRUS Subject RIV: CE - Biochemistry Impact factor: 9.202, year: 2015

  15. Human insulin-like growth factor II leader 2 mediates internal initiation of translation

    DEFF Research Database (Denmark)

    Pedersen, Susanne; Christiansen, Jan; Hansen, T.O.

    2002-01-01

    Insulin-like growth factor II (IGF-II) is a fetal growth factor, which belongs to the family of insulin-like peptides. During fetal life, the IGF-II gene generates three mRNAs with different 5' untranslated regions (UTRs), but identical coding regions and 3' UTRs. We have shown previously that IG...

  16. Speech Delay and Its Affecting Factors (Case Study in a Child with Initial Aq)

    Science.gov (United States)

    Syamsuardi

    2015-01-01

    Any parent wishes an appropriate development for their children. One of the parents' great concerns is the children's speech development; they are worried if their children are late to speak. The children's speech development is influenced by physical and environmental factors. The causes of physical factors are related to the problem but the role…

  17. Risk factors for discordant immune response among HIV-infected patients initiating antiretroviral therapy: A retrospective cohort study

    Directory of Open Access Journals (Sweden)

    B P Muzah

    2012-10-01

    Full Text Available Background. The therapeutic goal of antiretroviral therapy (ART is sustained immune recovery and viral suppression. However, some patients experience poor CD4 cell count responses despite achieving viral suppression. Such discordant immune responses have been associated with poor clinical outcomes. Objective. We aimed to determine the prevalence of discordant immune response and explore associated factors in a retrospective cohort of patients attending 2 large public sector clinics, during the 6 months following ART initiation. Methods. Data were analysed from 810 HIV-infected adults initiated on first-line ART at 2 clinics in Johannesburg, between 1 November 2008 and 31 December 2009. Multivariate logistic regression models were used to estimate adjusted odds ratios (AORs to determine associations between discordant immune response and clinical and demographic factors. Results. At ART initiation, 65% (n=592 of participants were female, with a mean age of 38.5 years. Median baseline CD4 cell count was 155 cells/mm3, 70% (n=645 of patients had a haemoglobin level >11 g/dl and 88% (n=803 were initiated on stavudine-lamivudine-efavirenz/nevirapine (D4T-3TC-EFV/NVP. Six months after ART initiation, 24% (n=220 of patients had a discordant immune response and 7% (n=67 a discordant virological response. On multivariate analysis, baseline CD cell count ≥200 cells/mm3 (AOR 3.02; 95% confidence interval (CI 2.08 - 4.38; p

  18. The HS2 enhancer of the beta-globin locus control region initiates synthesis of non-coding, polyadenylated RNAs independent of a cis-linked globin promoter.

    Science.gov (United States)

    Ling, Jianhua; Baibakov, Boris; Pi, Wenhu; Emerson, Beverly M; Tuan, Dorothy

    2005-07-29

    The HS2 enhancer in the beta-globin locus control region (LCR) regulates transcription of the globin genes 10-50 kb away. Earlier studies show that a transcription mechanism initiated by the HS2 enhancer through the intervening DNA in the direction of the cis-linked promoter and gene mediates long-range enhancer function. Here, we further analyzed the enhancer-initiated RNAs and their mode of transcription from the HS2 enhancer in the endogenous genome of erythroid K562 cells, in plasmids integrated into K562 cells and in purified DNA used as template in in vitro transcription reactions. We found that the HS2 enhancer was able to initiate transcription autonomously in the absence of a cis-linked globin promoter. The enhancer-initiated, intergenic RNAs were different from the mRNA synthesized at the promoter in several aspects. The enhancer RNAs were synthesized not from a defined site but from multiple sites both within and as far as 1 kb downstream of the enhancer. The enhancer RNAs did not appear to contain a normal cap structure at the 5' ends. They were polyadenylated at multiple sites within 3 kb downstream of their initiation sites and were therefore shorter than 3 kb in lengths. The enhancer RNAs remained in discrete spots within the nucleus and were not processed into mRNA or translated into proteins. These particular features of enhancer-initiated transcription indicate that the transcriptional complex assembled by the enhancer was different from the basal transcription complex assembled at the promoter. The results suggest that in synthesizing non-coding, intergenic RNAs, the enhancer-assembled transcription complex could track through the intervening DNA to reach the basal promoter complex and activate efficient mRNA synthesis from the promoter.

  19. Fibroblast growth factor 23 inhibits extrarenal synthesis of 1,25-dihydroxyvitamin D in human monocytes.

    Science.gov (United States)

    Bacchetta, Justine; Sea, Jessica L; Chun, Rene F; Lisse, Thomas S; Wesseling-Perry, Katherine; Gales, Barbara; Adams, John S; Salusky, Isidro B; Hewison, Martin

    2013-01-01

    Vitamin D is a potent stimulator of monocyte innate immunity, and this effect is mediated via intracrine conversion of 25-hydroxyvitamin D (25OHD) to 1,25-dihydroxyvitamin D (1,25(OH)(2) D). In the kidney, synthesis of 1,25(OH)(2) D is suppressed by fibroblast growth factor 23 (FGF23), via transcriptional suppression of the vitamin D-activating enzyme 1α-hydroxylase (CYP27B1). We hypothesized that FGF23 also suppresses CYP27B1 in monocytes, with concomitant effects on intracrine responses to 1,25(OH)(2) D. Healthy donor peripheral blood mononuclear cell monocytes (PBMCm) and peritoneal dialysate monocyte (PDm) effluent from kidney disease patients were assessed at baseline to confirm the presence of mRNA for FGF23 receptors (FGFRs), with Klotho and FGFR1 being more strongly expressed than FGFR2/3/4 in both cell types. Immunohistochemistry showed coexpression of Klotho and FGFR1 in PBMCm and PDm, with this effect being enhanced following treatment with FGF23 in PBMCm but not PDm. Treatment with FGF23 activated mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) pathways in PBMCm, demonstrating functional FGFR signaling in these cells. FGF23 treatment of PBMCm and PDm decreased expression of mRNA for CYP27B1. In PBMCm this was associated with downregulation of 25OHD to 1,25(OH)(2) D metabolism, and concomitant suppression of intracrine induced 24-hydroxylase (CYP24A1) and antibacterial cathelicidin (LL37). FGF23 suppression of CYP27B1 was particularly pronounced in PBMCm treated with interleukin-15 to stimulate synthesis of 1,25(OH)(2) D. These data indicate that FGF23 can inhibit extra-renal expression of CYP27B1 and subsequent intracrine responses to 1,25(OH)(2) D in two different human monocyte models. Elevated expression of FGF23 may therefore play a crucial role in defining immune responses to vitamin D and this, in turn, may be a key determinant of infection in patients with chronic kidney disease (CKD). Copyright © 2013 American Society for

  20. Optimising Translational Research Opportunities: A Systematic Review and Narrative Synthesis of Basic and Clinician Scientists' Perspectives of Factors Which Enable or Hinder Translational Research.

    Directory of Open Access Journals (Sweden)

    Nina Fudge

    Full Text Available Translational research is central to international health policy, research and funding initiatives. Despite increasing use of the term, the translation of basic science discoveries into clinical practice is not straightforward. This systematic search and narrative synthesis aimed to examine factors enabling or hindering translational research from the perspective of basic and clinician scientists, a key stakeholder group in translational research, and to draw policy-relevant implications for organisations seeking to optimise translational research opportunities.We searched SCOPUS and Web of Science from inception until April 2015 for papers reporting scientists' views of the factors they perceive as enabling or hindering the conduct of translational research. We screened 8,295 papers from electronic database searches and 20 papers from hand searches and citation tracking, identifying 26 studies of qualitative, quantitative or mixed method designs. We used a narrative synthesis approach and identified the following themes: 1 differing concepts of translational research 2 research processes as a barrier to translational research; 3 perceived cultural divide between research and clinical care; 4 interdisciplinary collaboration as enabling translation research, but dependent on the quality of prior and current social relationships; 5 translational research as entrepreneurial science. Across all five themes, factors enabling or hindering translational research were largely shaped by wider social, organisational, and structural factors.To optimise translational research, policy could consider refining translational research models to better reflect scientists' experiences, fostering greater collaboration and buy in from all types of scientists. Organisations could foster cultural change, ensuring that organisational practices and systems keep pace with the change in knowledge production brought about by the translational research agenda.

  1. Synthesis of platelet-activating factor by human blood platelets and leucocytes. Evidence against selective utilization of cellular ether-linked phospholipids

    NARCIS (Netherlands)

    Sturk, A.; Schaap, M. C.; Prins, A.; ten Cate, J. W.; van den Bosch, H.

    1989-01-01

    Synthesis of platelet activating factor (PAF) in blood platelet suspensions may be due to leucocyte contamination. We therefore investigated PAF synthesis in human blood platelet suspensions and granulocyte- (PMN)-enriched leucocyte suspensions upon stimulation by thrombin and Ca2+-ionophore A23187,

  2. Factors predicting Behavior Management Problems during Initial Dental Examination in Children Aged 2 to 8 Years

    OpenAIRE

    Sharma, Arun; Kumar, Dipanshu; Anand, Ashish; Mittal, Vipula; Singh, Aparna; Aggarwal, Nidhi

    2017-01-01

    Aim The aim of the present study was to identify the various background variables and its influence on behavior management problems (BMP) in children. Materials and methods The study included 165 children aged 2 to 8 years. During the initial dental visit, an experienced operator obtained each child?s background variables from accompanying guardians using a standardized questionnaire. Children?s dental behavior was rated by Frankel behavior rating scale. The behavior was then analyzed in rela...

  3. Pharmacological properties of granulocytic colony-stimulating factor pegylated using electron beam synthesis nanotechnologies.

    Science.gov (United States)

    Dygai, A M; Zyuz'kov, G N; Zhdanov, V V; Madonov, P G; Udut, E V; Miroshnichenko, L A; Khrichkova, T Yu; Simanina, E V; Stavrova, L A; Artamonov, A V; Bekarev, A A; Kinsht, D N; Chaikovskiy, A V; Markova, T S; Gurto, R V

    2011-11-01

    Granulocytic CSF pegylated using electron-beam synthesis nanotechnology exhibits pronounced granulomonocytopoiesis-stimulating and SC-mobilizing activity. More potent stimulation of committed precursors against the background of less pronounced activation of polypotent hemopoietic cells is a peculiarity of hemostimulating action of pegylated using electron-beam synthesis nanotechnology granulocytic CSF in comparison with its non-modified analog. The mobilizing effect of pegylated using electron-beam synthesis nanotechnology granulocytic CSF on early progenitor elements surpasses that of non-conjugated cytokine.

  4. Members of the LBD Family of Transcription Factors Repress Anthocyanin Synthesis and Affect Additional Nitrogen Responses in Arabidopsis

    OpenAIRE

    Rubin, G.; Tohge, T.; Matsuda, F.; Saito, K.; Scheible, W.

    2009-01-01

    Nitrogen (N) and nitrate (NO3-) per se regulate many aspects of plant metabolism, growth, and development. N/NO3- also suppresses parts of secondary metabolism, including anthocyanin synthesis. Molecular components for this repression are unknown. We report that three N/NO3--induced members of the LATERAL ORGAN BOUNDARY DOMAIN (LBD) gene family of transcription factors (LBD37, LBD38, and LBD39) act as negative regulators of anthocyanin biosynthesis in Arabidopsis thaliana. Overexpression of e...

  5. Visual field progression in the Collaborative Initial Glaucoma Treatment Study the impact of treatment and other baseline factors.

    Science.gov (United States)

    Musch, David C; Gillespie, Brenda W; Lichter, Paul R; Niziol, Leslie M; Janz, Nancy K

    2009-02-01

    To evaluate factors associated with visual field (VF) progression, using all available follow-up through 9 years after treatment initiation, in the Collaborative Initial Glaucoma Treatment Study (CIGTS). Longitudinal follow-up of participants enrolled in a randomized clinical trial. Six hundred seven newly diagnosed glaucoma patients. In a randomized clinical trial, 607 subjects with newly diagnosed open-angle glaucoma initially were treated with either medication or trabeculectomy. After treatment initiation and early follow-up, subjects were evaluated clinically at 6-month intervals. Study participants in both arms of the CIGTS were treated aggressively in an effort to reduce intraocular pressure (IOP) to a level at or below a predetermined, eye-specific target pressure. Visual field progression was analyzed using repeated measures models. Visual field progression, measured by Humphrey 24-2 full-threshold testing and assessed by the change in the mean deviation (MD), and an indicator of substantial worsening of the VF (MD decrease of > or =3 dB from baseline), assessed at each follow-up visit. Follow-up indicated minimal change from baseline in each initial treatment group's average MD. However, at the 8-year follow-up examination, substantial worsening (> or =3 dB) of MD from baseline was found in 21.3% and 25.5% of the initial surgery and initial medicine groups, respectively. The effect of initial treatment on subsequent VF loss was modified by time (Ppresentation, but detrimental for patients with diabetes, are noteworthy and warrant independent confirmation. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

  6. Re-Imagining Initial Multiracial Teacher Education (IMTE) Model through the ODL Philosophy: A Critical Qualitative Meta-Synthesis Study

    Science.gov (United States)

    Nyoni, J.

    2012-01-01

    This article reports on a critical meta-analysis of empirical studies done by human sciences researchers on the initial multicultural teacher education (IMTE) models in multicultural post-colonial transitional societies with reference to sub-Saharan African states in general and South Africa in particular. Using a critical post-positivist…

  7. Factors Influencing the Initiation of Smokeless Tobacco Consumption Among Low Socioeconomic Community in Bangladesh: A Qualitative Investigation.

    Science.gov (United States)

    Shahjahan, Md; Harun, Md Golam Dostogir; Chowdhury, A B M Alauddin; Ahmed, Kapil; Khan, Hafiz T A

    2017-07-01

    This study explored factors influencing the initiation of smokeless tobacco (SLT) consumption in a low socioeconomic urban community in Bangladesh. The study conducted four focus group discussions among 33 informants involves school teachers, community leaders, women, and betel-nut shops owners. The results were prepared by thematic analysis of the transcripts where informants mean age was 30 ( SD ± 6.8) years with varying level of education. Tradition of hospitality, curiosity, offer from an elderly person, and avoiding nausea during pregnancy and at time of quitting smoking were key factors for the initiation of SLT consumption. The results also revealed most people were aware about the danger of SLT consumption but, in practice, consumed frequently. The research suggested that doctors might advise people not to use any form of SLT while they seeking health services. Furthermore, community-based awareness program could minimize the wider use of SLT among low-income community in Bangladesh.

  8. The transcription factor TCF-1 initiates the differentiation of T(FH) cells during acute viral infection.

    Science.gov (United States)

    Xu, Lifan; Cao, Yi; Xie, Zhunyi; Huang, Qizhao; Bai, Qiang; Yang, Xia; He, Ran; Hao, Yaxing; Wang, Haoqiang; Zhao, Tingting; Fan, Zhonglei; Qin, Aijian; Ye, Jianqiang; Zhou, Xinyuan; Ye, Lilin; Wu, Yuzhang

    2015-09-01

    Induction of the transcriptional repressor Bcl-6 in CD4(+) T cells is critical for the differentiation of follicular helper T cells (T(FH) cells), which are essential for B cell-mediated immunity. In contrast, the transcription factor Blimp1 (encoded by Prdm1) inhibits T(FH) differentiation by antagonizing Bcl-6. Here we found that the transcription factor TCF-1 was essential for both the initiation of T(FH) differentiation and the effector function of differentiated T(FH) cells during acute viral infection. Mechanistically, TCF-1 bound directly to the Bcl6 promoter and Prdm1 5' regulatory regions, which promoted Bcl-6 expression but repressed Blimp1 expression. TCF-1-null T(FH) cells upregulated genes associated with non-T(FH) cell lineages. Thus, TCF-1 functions as an important hub upstream of the Bcl-6-Blimp1 axis to initiate and secure the differentiation of T(FH) cells during acute viral infection.

  9. Motivational factors for initiating, implementing, and maintaining physical activity behavior following a rehabilitation program for patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Walker, Karen Christina; Valentiner, Laura Staun; Langberg, Henning

    2018-01-01

    motivation. Finally, enjoyment of the activity was determining for long-term maintenance of physical activity behavior. Conclusion: Satisfaction of innate psychological needs leads to more autonomous regulation of behavior and, through this study, we investigated determining factors for extrinsically......Aim: To explore motivational factors for initiating, implementing, and maintaining physical activity following a rehabilitation program for patients with type 2 diabetes mellitus. Methods: Semi-structured, individual, qualitative interviews with five informants from the InterWalk trial were...... to guide analysis after identification of preliminary themes. Results: Commitment and obligation were emphasized as being motivational in initiating physical activity. Toward the termination of the program, this was challenged by an expressed need for autonomy. Successful behavioral change...

  10. Great Lakes water quality initiative technical support document for the procedure to determine bioaccumulation factors. Draft report

    International Nuclear Information System (INIS)

    1993-03-01

    The purpose of the document is to provide the technical information and rationale in support of the proposed procedures to determine bioaccumulation factors. Bioaccumulation factors, together with the quantity of aquatic organisms eaten, determine the extent to which people and wildlife are exposed to chemicals through the consumption of aquatic organisms. The more bioaccumulative a pollutant is, the more important the consumption of aquatic organisms becomes as a potential source of contaminants to humans and wildlife. Bioaccumulation factors are needed to determine both human health and wildlife tier I water quality criteria and tier II values. Also, they are used to define Bioaccumulative Chemicals of Concern among the Great Lakes Initiative universe of pollutants. Bioaccumulation factors range from less than one to several million

  11. Signature of protein adaptation to warm deep sea environments: the case of Initiation Factor 6 studied by molecular simulation and neutron scattering

    International Nuclear Information System (INIS)

    Calligari, Paolo

    2008-01-01

    The protein Initiation Factor 6 (IF6) takes part in the protein synthesis regulation of several organisms. It was also found in archeaebacteria such as Methanococcus jannaschii which lives in deep-seas near hydrothermal vents where temperature reaches 80 C and pressure is between 250 bar and 500 bar. The aim of this work was to study for the first time dynamical and structural properties of IF6 produced by M. jannaschii and comparing them with those of the IF6 homologue present in Saccharomyces cerevisiae which lives at 'normal' environmental conditions (27 C and 1 bar). Molecular simulation gave here new insights into the adaptation of these two proteins to their respective physiological conditions and showed that the latter induced similar dynamical and structural properties: in their respective 'natural' conditions, IF6s show very similar structural fluctuations and the characteristic relaxation times which define their dynamical properties shows similar changes when comparing unfavorable conditions to physiological ones. The creation of these corresponding states between the two homologues has been interpreted by the fractional Brownian dynamics model and by a novel method for the characterization of protein secondary structures. The latter is presented here in detail together with some examples of other applications. Experimental data obtained from quasi-elastic neutron scattering seemed to support the results obtained by molecular simulations. (author) [fr

  12. Novel microwave initiated synthesis of Zn{sub 2}SiO{sub 4} and MCrO{sub 4} (M = Ca, Sr, Ba, Pb)

    Energy Technology Data Exchange (ETDEWEB)

    Parhi, Purnendu [Department of Mechanical Engineering, Colorado State University, Fort Collins 80523 (United States); Manivannan, V. [Department of Mechanical Engineering, Colorado State University, Fort Collins 80523 (United States)], E-mail: mani@engr.colostate.edu

    2009-02-05

    A novel microwave initiated solid-state metathesis synthesis of metal chromates and zinc silicate has been investigated. The high lattice energy of NaCl drives the solid-state metathesis reaction (CaCl{sub 2}.2H{sub 2}O + Na{sub 2}CrO{sub 4}.4H{sub 2}O {yields} NaCl + CaCrO{sub 4} + 6H{sub 2}O{up_arrow}) in the forward direction to obtain the products. The structural, optical, and chemical properties of synthesized compounds are determined by powder X-ray diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy, and diffused reflectance spectroscopy in the UV-vis range.

  13. Depression and Alzheimer's disease: is stress the initiating factor in a common neuropathological cascade?

    DEFF Research Database (Denmark)

    Aznar, Susana; Knudsen, Gitte M

    2011-01-01

    The existence of a high co-morbidity between Alzheimer's disease (AD) and depression has been known for a long time. More interesting though are recent studies indicating that depression and number of depressive episodes earlier in life is associated with increased risk of AD development....... This suggests the existence of common neuropathological mechanisms behind depression and AD. Here we propose that the brain changes associated with depressive episodes that compromise the brain's ability to cope with stress may constitute risk factors for development of AD. Furthermore, in individuals...... serotonergic and cholinergic system, hypothalamic-pituitary-adrenal axis and brain derived neurotrophic factor, and discussed in relation to AD....

  14. Risk factors associated with increased mortality among HIV infected children initiating antiretroviral therapy (ART in South Africa.

    Directory of Open Access Journals (Sweden)

    Brian C Zanoni

    Full Text Available OBJECTIVE: To identify demographic and clinical risk factors associated with mortality after initiation of antiretroviral therapy (ART in a cohort of human immunodeficiency (HIV infected children in KwaZulu-Natal, South Africa. METHODS: We performed a retrospective cohort study of 537 children initiating antiretroviral therapy at McCord Hospital in KwaZulu-Natal, South Africa. Data were extracted from electronic medical records and risk factors associated with mortality were assessed using Cox regression analysis. RESULTS: Overall there were 47 deaths from the cohort of 537 children initiating ART with over 991 child-years of follow-up (median 22 months on ART, yielding a mortality rate of 4.7 deaths per 100 child years on ART. Univariate analysis indicated that mortality was significantly associated with lower weight-for-age Z-score (p<0.0001, chronic diarrhea (p = 0.0002, lower hemoglobin (p = 0.002, age <3 years (p = 0.003, and CD4% <10% (p = 0.005. The final multivariable Cox proportional hazards mortality model found age less than 3 years (p = 0.004, CD4 <10% (p = 0.01, chronic diarrhea (p = 0.03, weight-for-age Z-score (<0.0001 and female gender as a covariate varying with time (p = 0.03 all significantly associated with mortality. CONCLUSION: In addition to recognized risk factors such as young age and advanced immunosuppression, we found female gender to be significantly associated with mortality in this pediatric ART cohort. Future studies are needed to determine whether intrinsic biologic differences or socio-cultural factors place female children with HIV at increased risk of death following initiation of ART.

  15. Prenatal Care Initiation in Low-Income Hispanic Women: Risk and Protective Factors

    Science.gov (United States)

    Luecken, Linda J.; Purdom, Catherine L.; Howe, Rose

    2009-01-01

    Objectives: To examine the psychosocial risk (distress, stress, unintended pregnancy) and protective factors (social support, mastery, familism) associated with entry into prenatal care among low-income Hispanic women. Methods: Between April and September 2005, 483 postpartum Medicaid-eligible Hispanic women completed a survey at the hospital.…

  16. ABCE1: A special factor that orchestrates translation at the crossroad between recycling and initiation

    Czech Academy of Sciences Publication Activity Database

    Mancera-Martínez, E.; Brito Querido, J.; Valášek, Leoš Shivaya; Simonetti, A.; Hashem, Y.

    2017-01-01

    Roč. 14, č. 10 (2017), s. 1279-1285 ISSN 1547-6286 R&D Projects: GA ČR(CZ) GA14-05394S Institutional support: RVO:61388971 Keywords : ABCE1 * cryo-EM * ribosome Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 3.900, year: 2016

  17. XPS and factor analysis study of initial stages of cerium oxide growth on polycrystalline tungsten

    Czech Academy of Sciences Publication Activity Database

    Polyak, Yaroslav; Bastl, Zdeněk

    2015-01-01

    Roč. 47, č. 6 (2015), s. 663-671 ISSN 0142-2421 Institutional support: RVO:68378271 ; RVO:61388955 Keywords : XPS * FA * PLD * cerium oxide * WO 3 * Ce (3d) Subject RIV: CF - Physical ; Theoretical Chemistry; CF - Physical ; Theoretical Chemistry (UFCH-W) Impact factor: 1.018, year: 2015

  18. CARDIOVASCULAR RISK FACTORS IN MEDICAL UNIVERSITY STUDENTS (RESEARCH WITHIN INTERNATIONAL PROJECT MAY MEASUREMENT MONTH INITIATIVE

    Directory of Open Access Journals (Sweden)

    Анастасия Михайловна Кочергина

    2018-03-01

    Full Text Available Subject of study. Arterial hypertension and other cardiovascular risk factors in students of medical universities. Aim – to determine incidence of arterial hypertension and modifiable cardiovascular risk factors in students of medical university. Methods. The study included 146 students of KemSMU, as well as 67 students of SamSMU who were surveyed during May 1-10, 2017 within the framework of the international project «MAY MEASUREMENT MONTH 2017 (MMM17» using a standard questionnaire supplemented with a developed questionnaire including questions about the daily consumption of coffee and energy drinks, the amount of vegetables and fruits consumed, salt, physical activity level and night duty as paramedical personnel. All students underwent a three-fold measurement of blood pressure (BP after 5 minutes of rest sitting. Results. The frequency of arterial hypertension among KemSMU students at the age of 22.04 ± 1.8 years is 4.1 %, among the SamSMU students at the age of 21.2 ± 0.73 years – 1.5 %. Individuals with arterial hypertension – more often men gender who regularly drink coffee. Male students have a higher incidence of several risk factors than female students. The high frequency of tabacco smoking among medical students (13 % – KemSMU, 7.5 % – SamSMU was detected, while 31.6 % of all smokers began to smoke during their studies. Conclusions. The most common risk factors determined among students were smoking, increased intake of salt. Young men significantly more often demonstrated the presence of risk factors than women of similar age.

  19. Impact of individual and market factors on the timing of initiation of hospice terminal care.

    Science.gov (United States)

    Christakis, N A; Iwashyna, T J

    2000-05-01

    Hospice terminal care is now used by 10% to 15% of elderly Americans at variable points before their deaths. By examining the duration of patient survival after enrollment in hospice care, we sought to identify individual and market factors associated with the timing of hospice use. We linked Medicare claims, census information, and Area Resource File data to form a national cohort of 151,410 hospice patients admitted in 1993 and followed up until late 1996. We examined this cohort with Cox regression and other means. The primary outcome measure was survival after hospice enrollment. The patients had a mean +/- SD age of 79.0 +/- 7.4 years; 10.2% were nonwhite; 51.4% were female; and 71.3% had cancer. Median survival after hospice enrollment was 30 days (interquartile range, 10-86 days). After adjustment for measured patient, provider, and market factors, several variables were associated with relatively earlier hospice enrollment, farther from death. Compared with complementary groups, nonwhites were enrolled in hospice 4 days earlier; women, 5 days earlier; older people, 1 day earlier; and those with substance abuse, psychiatric disease, or dementia, each 3 days earlier. After adjustment, income and education were not associated with the timing of enrollment. Patients residing in markets with more hospital beds, greater hospice capacity, or a higher proportion of generalists were enrolled earlier. Even after adjustment for certain clinical attributes, individual social factors and local market factors were associated with survival after hospice enrollment. Certain socially disadvantaged groups were enrolled earlier, as were those residing in areas with more medical institutions. The decision to enroll patients in hospice may depend on both nonclinical and clinical factors.

  20. Prognostic factors of a good response to initial therapy in children and adolescents with differentiated thyroid cancer

    Science.gov (United States)

    Vaisman, Fernanda; Bulzico, Daniel Alves; Pessoa, Cencita Hosannah Cordeiro Noronha; Bordallo, Maria Alice Neves; de Mendonça, Ullyanov Bezerra Toscano; Dias, Fernando Luiz; Coeli, Claudia Medina; Corbo, Rossana; Vaisman, Mario

    2011-01-01

    BACKGROUND: Therapeutic approaches in pediatric populations are based on adult data because there is a lack of appropriate data for children. Consequently, there are many controversies regarding the proper treatment of pediatric patients. OBJECTIVE: The present study was designed to evaluate patients with differentiated thyroid carcinoma diagnosed before 20 years of age and to determine the factors associated with the response to the initial therapy. METHODS: Sixty‐five patients, treated in two tertiary‐care referral centers in Rio de Janeiro between 1980 and 2005 were evaluated. Information about clinical presentation and the response to initial treatment was analyzed and patients had their risk stratified in Tumor‐Node‐ Metastasis; Age‐Metastasis‐Extracapsular‐Size; distant Metastasis‐Age‐Completeness of primary tumor resection‐local Invasion‐Size and American‐Thyroid‐Association classification RESULTS: Patients ages ranged from 4 to 20 years (median 14). The mean follow‐up was 12,6 years. Lymph node metastasis was found in 61.5% and indicated a poor response to initial therapy, with a significant impact on time for achieving disease free status (p = 0.014 for response to initial therapy and p<0,0001 for disease‐free status in follow‐up). Distant metastasis was a predictor of a poor response to initial therapy in these patients (p = 0.014). The risk stratification systems we analyzed were useful for high-risk patients because they had a high sensitivity and negative predictive value in determining the response to initial therapy. CONCLUSIONS: Metastases, both lymph nodal and distant, are important predictors of the persistence of disease after initial therapy in children and adolescents with differentiated thyroid cancer. PMID:21484047

  1. Prognostic factors of a good response to initial therapy in children and adolescents with differentiated thyroid cancer

    Directory of Open Access Journals (Sweden)

    Fernanda Vaisman

    2011-01-01

    Full Text Available BACKGROUND: Therapeutic approaches in pediatric populations are based on adult data because there is a lack of appropriate data for children. Consequently, there are many controversies regarding the proper treatment of pediatric patients. OBJECTIVE: The present study was designed to evaluate patients with differentiated thyroid carcinoma diagnosed before 20 years of age and to determine the factors associated with the response to the initial therapy. METHODS: Sixty-five patients, treated in two tertiary-care referral centers in Rio de Janeiro between 1980 and 2005 were evaluated. Information about clinical presentation and the response to initial treatment was analyzed and patients had their risk stratified in Tumor-Node- Metastasis; Age-Metastasis-Extracapsular-Size; distant Metastasis-Age-Completeness of primary tumor resection-local Invasion-Size and American-Thyroid-Association classification RESULTS: Patients ages ranged from 4 to 20 years (median 14. The mean follow-up was 12,6 years. Lymph node metastasis was found in 61.5% and indicated a poor response to initial therapy, with a significant impact on time for achieving disease free status (p = 0.014 for response to initial therapy and p<0,0001 for disease-free status in follow-up. Distant metastasis was a predictor of a poor response to initial therapy in these patients (p = 0.014. The risk stratification systems we analyzed were useful for high-risk patients because they had a high sensitivity and negative predictive value in determining the response to initial therapy. CONCLUSIONS: Metastases, both lymph nodal and distant, are important predictors of the persistence of disease after initial therapy in children and adolescents with differentiated thyroid cancer.

  2. Curricular initiatives that enhance student knowledge and perceptions of sexual and gender minority groups: a critical interpretive synthesis

    Directory of Open Access Journals (Sweden)

    Jennifer Desrosiers

    2016-10-01

    Conclusions: The literature is limited to the evaluation of explicit curricula. The wider cultural competence literature offers further insight by highlighting the importance of broad and embedded forces including social influences, the institutional climate, and the implicit, or hidden, curriculum. A combined interpretation of the complementary cultural competence and sexual and gender diversity literature provides a novel understanding of the optimal content and context for the delivery of a successful curricular initiative.

  3. Factorization and the synthesis of optimal feedback kernels for differential-delay systems

    Science.gov (United States)

    Milman, Mark M.; Scheid, Robert E.

    1987-01-01

    A combination of ideas from the theories of operator Riccati equations and Volterra factorizations leads to the derivation of a novel, relatively simple set of hyperbolic equations which characterize the optimal feedback kernel for the finite-time regulator problem for autonomous differential-delay systems. Analysis of these equations elucidates the underlying structure of the feedback kernel and leads to the development of fast and accurate numerical methods for its computation. Unlike traditional formulations based on the operator Riccati equation, the gain is characterized by means of classical solutions of the derived set of equations. This leads to the development of approximation schemes which are analogous to what has been accomplished for systems of ordinary differential equations with given initial conditions.

  4. Decreasing Eukaryotic Initiation Factor 3C (EIF3C) Suppresses Proliferation and Stimulates Apoptosis in Breast Cancer Cell Lines Through Mammalian Target of Rapamycin (mTOR) Pathway.

    Science.gov (United States)

    Zhao, Weipeng; Li, Xichuan; Wang, Jun; Wang, Chen; Jia, Yongsheng; Yuan, Shunzong; Huang, Yong; Shi, Yehui; Tong, Zhongsheng

    2017-08-30

    BACKGROUND Translation initiation is the rate limiting step of protein synthesis and is highly regulated. Eukaryotic initiation factor 3C (EIF3C), an oncogene overexpressed in several human cancers, plays an important role in tumorigenesis and cell proliferation. MATERIAL AND METHODS Immunohistochemistry was used to determine the expression of EIF3C in breast cancer tissues from 42 patients. We investigated whether EIF3C silencing decreases breast cancer cell proliferation as assessed by colony formation assay, and whether EIF3C gene knockdown induces apoptosis as assessed by flow cytometry analysis. We utilized the stress and apoptosis signaling antibody array kit, while p-ERK1/2, p-Akt, p-Smad2, p-p38 MAPK, cleaved caspase-3, and cleaved caspase-7 were explored between EIF3C-siRNA and controls. Furthermore, the effects of EIF3C gene knockdown in mTOR pathway were analyzed by western blotting for different cell lines. RESULTS In EIF3C-positive tumors, 32 out of 42 showed significantly higher frequencies of high grade group by immunoreactivity (p=0.0016). BrdU incorporation after four days of cell plating was significantly suppressed in MDA-MB-231 cells by EIF3C knockdown compared with controls, with average changes of 7.8-fold (pcells by EIF3C knockdown compared with controls (pCell apoptosis was significantly increased in the EIF3C-siRNA group when compared with the cells that were transfected with scrambled siRNA (3.51±0.0842 versus 13.24±0.2307, p<0.01). The mTOR signaling pathway was involved in decreasing EIF3C translational efficiency. CONCLUSIONS Unveiling the mechanisms of EIF3 action in tumorigenesis may help identify attractive targets for cancer therapy.

  5. Automated work packages architecture: An initial set of human factors and instrumentation and controls requirements

    Energy Technology Data Exchange (ETDEWEB)

    Agarwal, Vivek [Idaho National Lab. (INL), Idaho Falls, ID (United States); Oxstrand, Johanna H. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Le Blanc, Katya L. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2014-09-01

    The work management process in current fleets of national nuclear power plants is so highly dependent on large technical staffs and quality of work instruction, i.e., paper-based, that this puts nuclear energy at somewhat of a long-term economic disadvantage and increase the possibility of human errors. Technologies like mobile portable devices and computer-based procedures can play a key role in improving the plant work management process, thereby increasing productivity and decreasing cost. Automated work packages are a fundamentally an enabling technology for improving worker productivity and human performance in nuclear power plants work activities because virtually every plant work activity is accomplished using some form of a work package. As part of this year’s research effort, automated work packages architecture is identified and an initial set of requirements identified, that are essential and necessary for implementation of automated work packages in nuclear power plants.

  6. Function of Brg1 Chromatin Remodeling Factor in Sonic Hedgehog-Dependent Medulloblastoma Initiation and Maintenance

    Science.gov (United States)

    2015-12-01

    neural precursor proliferation. Genes Dev 2009; 23: 2729-2741. 14 Flora A, Klisch TJ, Schuster G, Zoghbi HY. Deletion of Atoh1 disrupts Sonic Hedgehog...29 Klisch TJ, Xi Y, Flora A, Wang L, Li W, Zoghbi HY. In vivo Atoh1 targetome reveals how a proneural transcription factor regulates cerebellar... definitively exclude the possibility that Hck phosphorylates other Gli1 regulators and activates Gli1 indirectly. In the study, we observed that Hck

  7. In vivo deletion analysis of the architecture of a multiprotein complex of translation initiation factors

    Czech Academy of Sciences Publication Activity Database

    Nielsen, K. H.; Valášek, Leoš

    2007-01-01

    Roč. 431, - (2007), s. 15-32 ISSN 0076-6879 Grant - others:US(US) Wellcome Trust Grant 076456/Z/05/Z; US(US) R01 TW007271 Institutional research plan: CEZ:AV0Z50200510 Source of funding: N - neverejné zdroje ; N - neverejné zdroje Keywords : translation * multiprotein complex * eif3 Subject RIV: EE - Microbiology, Virology Impact factor: 2.122, year: 2007

  8. Risk factors for, and prevention of, shoulder injuries in overhead sports: a systematic review with best-evidence synthesis.

    Science.gov (United States)

    Asker, Martin; Brooke, Hannah L; Waldén, Markus; Tranaeus, Ulrika; Johansson, Fredrik; Skillgate, Eva; Holm, Lena W

    2018-03-26

    To assess the evidence for risk factors and prevention measures for shoulder injuries in overhead sports. Systematic review with best-evidence synthesis. Medline (Ovid), PubMed (complementary search), Embase (Elsevier), Cochrane (Wiley), SPORTDiscus (Ebsco) and Web of Science Core Collection (Thomson Reuters), from 1 January 1990 to 15 May 2017. Randomised controlled trials, cohort studies and case-control studies on risk factors or prevention measures for shoulder injuries in overhead sports. The eligible studies were quality assessed using the Scottish Intercollegiate Guidelines Network criteria. Of 4778 studies identified, 38 were eligible for quality review and 17 met the quality criteria to be included in the evidence synthesis. One additional quality study presented a shoulder injury prevention programme. Most studies focused on baseball, lacrosse or volleyball (n=13). The risk factors examined included participation level (competition vs training) (n=10), sex (n=4), biomechanics (n=2) and external workload (n=2). The evidence for all risk factors was limited or conflicting. The effect of the prevention programme within the subgroup of uninjured players at baseline was modest and possibly lacked statistical power. All investigated potential risk factors for shoulder injury in overhead sports had limited evidence, and most were non-modifiable (eg, sex). There is also limited evidence for the effect of shoulder injury prevention measures in overhead sports. CRD42015026850. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. A Review of the Factors Associated With the Timely Initiation of Breastfeeding and Exclusive Breastfeeding in the Middle East

    Directory of Open Access Journals (Sweden)

    Riyadh A Alzaheb

    2017-12-01

    Full Text Available Background: Breastfeeding supplies all the nutrients that infants need for their healthy development. Breastfeeding practice is multifactorial, and numerous variables influence mothers’ decisions and ability to breastfeed. This review identifies the factors potentially affecting the timely initiation of breastfeeding within an hour after birth and exclusive breastfeeding in the first 6 months in Middle Eastern countries. Methods: The Medline, ScienceDirect, and Web of Science databases were keyword-searched for primary studies meeting the following inclusion criteria: (1 publication in the English language between January 2001 and May 2017, (2 original research articles reporting primary data on the factors influencing the timely initiation of breastfeeding and/or exclusive breastfeeding, (3 the use of World Health Organization definitions, and (4 Middle Eastern research contexts. A random effect model was used to establish the average prevalence of the timely initiation of breastfeeding and exclusive breastfeeding in the Middle East. Results: The review identified 19 studies conducted in Saudi Arabia (7, Iran (3, Egypt (2, Turkey (2, Kuwait (1, the United Arab Emirates (1, Qatar (1, Lebanon (1, and Syria (1. The meta-analysis established that 34.3% (confidence interval [CI]: 20.2%-51.9% of Middle Eastern newborns received breastfeeding initiated within an hour of birth, and only 20.5% (CI: 14.5%-28.2% were fed only breast milk for the first 6 months. The 8 studies exploring breastfeeding initiation most commonly associated it with the following: delivery mode, maternal employment, rooming-in, and prelacteal feeding. The 17 studies investigating exclusive breastfeeding most frequently linked it to the following: maternal age, maternal education, maternal employment, and delivery mode. Conclusions: Middle Eastern health care organizations should fully understand all the determinants of breastfeeding identified by this review to provide

  10. Factors Associated With Initiation of Biologics in Patients With Axial Spondyloarthritis in an Urban Asian City: A PRESPOND Study.

    Science.gov (United States)

    Png, Wan Yu; Kwan, Yu Heng; Lee, Yi Xuan; Lim, Ka Keat; Chew, Eng Hui; Lui, Nai Lee; Tan, Chuen Seng; Thumboo, Julian; Østbye, Truls; Fong, Warren

    2018-04-05

    The aim of this study was to examine if patients' sociodemographic, clinical characteristics, and patient-reported outcomes were associated with biologics initiation in patients with axial spondyloarthritis in Singapore. Data from a dedicated registry from a tertiary referral center in Singapore from January 2011 to July 2016 were used. Initiation of first biologics was the main outcome of interest. Logistic regression analyses were used to explore the association of various factors on biologics initiation. Of 189 eligible patients (aged 37.7 ± 13.3 years; 76.2% were males), 30 (15.9 %) were started on biologics during follow-up. In the multivariable analysis model, age (odds ratio [OR]; 0.93; 95% confidence interval [CI], 0.89-0.98; P < 0.01), mental component summary score of Short-Form 36 Health Survey (OR, 0.18; 95% CI, 0.03-0.89; P = 0.04), erythrocyte sedimentation rate (OR, 1.02; 95% CI, 1.00-1.04; P = 0.02), presence of peptic ulcer disease (OR, 10.4; 95% CI, 2.21-48.8; P < 0.01), and lack of good response to nonsteroidal anti-inflammatory drugs (OR, 4.44; 95% CI, 1.63-12.1; P < 0.01) were found to be associated with biologics initiation. Age, erythrocyte sedimentation rate, mental component summary score, comorbidities of peptic ulcer disease, and responsiveness to nonsteroidal anti-inflammatory drugs were associated with biologics initiation. It is essential that clinicians recognize these factors in order to optimize therapy.

  11. A Review of the Factors Associated With the Timely Initiation of Breastfeeding and Exclusive Breastfeeding in the Middle East

    Science.gov (United States)

    Alzaheb, Riyadh A

    2017-01-01

    Background: Breastfeeding supplies all the nutrients that infants need for their healthy development. Breastfeeding practice is multifactorial, and numerous variables influence mothers’ decisions and ability to breastfeed. This review identifies the factors potentially affecting the timely initiation of breastfeeding within an hour after birth and exclusive breastfeeding in the first 6 months in Middle Eastern countries. Methods: The Medline, ScienceDirect, and Web of Science databases were keyword-searched for primary studies meeting the following inclusion criteria: (1) publication in the English language between January 2001 and May 2017, (2) original research articles reporting primary data on the factors influencing the timely initiation of breastfeeding and/or exclusive breastfeeding, (3) the use of World Health Organization definitions, and (4) Middle Eastern research contexts. A random effect model was used to establish the average prevalence of the timely initiation of breastfeeding and exclusive breastfeeding in the Middle East. Results: The review identified 19 studies conducted in Saudi Arabia (7), Iran (3), Egypt (2), Turkey (2), Kuwait (1), the United Arab Emirates (1), Qatar (1), Lebanon (1), and Syria (1). The meta-analysis established that 34.3% (confidence interval [CI]: 20.2%-51.9%) of Middle Eastern newborns received breastfeeding initiated within an hour of birth, and only 20.5% (CI: 14.5%-28.2%) were fed only breast milk for the first 6 months. The 8 studies exploring breastfeeding initiation most commonly associated it with the following: delivery mode, maternal employment, rooming-in, and prelacteal feeding. The 17 studies investigating exclusive breastfeeding most frequently linked it to the following: maternal age, maternal education, maternal employment, and delivery mode. Conclusions: Middle Eastern health care organizations should fully understand all the determinants of breastfeeding identified by this review to provide suitable

  12. Insulin-like growth factor I enhances proenkephalin synthesis and dopamine. beta. -hydroxylase activity in adrenal chromaffin cells

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, S.P. (Univ. of South Carolina School of Medicine, Columbia (USA))

    1991-01-01

    Insulin-like growth factor I (IGF-I) increased both the contents of proenkephalin derived enkephalin-containing peptides and the activity of dopamine {beta}-hydroxylase in bovine adrenal chromaffin cells. These increases in dopamine {beta}-hydroxylase and enkephalin-containing peptides continued for at least 8 days. The half-maximal IGF-I concentration for these effects was {approximately} 1 nM, with maximal effects observed at 10-30 nM. In contrast, insulin was 1,000-fold less potent. Pretreatment of chromaffin cells with IGF-I increased the rate of ({sup 35}S)proenkephalin synthesis 4-fold compared to untreated cells. Total protein synthesis increased only 1.5-fold under these conditions. These results suggest that IGF-I may be a normal regulator of chromaffin cell function.

  13. Individual, social, and environmental factors associated with initiating methamphetamine injection: implications for drug use and HIV prevention strategies.

    Science.gov (United States)

    Marshall, Brandon D L; Wood, Evan; Shoveller, Jean A; Buxton, Jane A; Montaner, Julio S G; Kerr, Thomas

    2011-06-01

    The purpose of this study was to determine the incidence and predictors of initiating methamphetamine injection among a cohort of injection drug users (IDU). We conducted a longitudinal analysis of IDU participating in a prospective study between June 2001 and May 2008 in Vancouver, Canada. IDU who had never reported injecting methamphetamine at the study's commencement were eligible. We used Cox proportional hazards models to identify the predictors of initiating methamphetamine injection. The outcome was time to first report of methamphetamine injection. Time-updated independent variables of interest included sociodemographic characteristics, drug use patterns, and social, economic and environmental factors. Of 1317 eligible individuals, the median age was 39.9 and 522 (39.6%) were female. At the study's conclusion, 200 (15.2%) participants had initiated injecting methamphetamine (incidence density: 4.3 per 100 person-years). In multivariate analysis, age (adjusted hazard ratio [aHR]: 0.96 per year older, 95%CI: 0.95-0.98), female sex (aHR: 0.58, 95%CI: 0.41-0.82), sexual abuse (aHR: 1.63, 95%CI: 1.18-2.23), using drugs in Vancouver's drug scene epicentre (aHR: 2.15 95%CI: 1.49-3.10), homelessness (aHR: 1.43, 95%CI: 1.01-2.04), non-injection crack cocaine use (aHR: 2.06, 95%CI: 1.36-3.14), and non-injection methamphetamine use (aHR: 3.69, 95%CI: 2.03-6.70) were associated with initiating methamphetamine injection. We observed a high incidence of methamphetamine initiation, particularly among young IDU, stimulant users, homeless individuals, and those involved in the city's open drug scene. These data should be useful for the development of a broad set of interventions aimed at reducing initiation into methamphetamine injection among IDU.

  14. Factors Associated With Interest in Same-Day Contraception Initiation Among Females in the Pediatric Emergency Department.

    Science.gov (United States)

    Miller, Melissa K; Randell, Kimberly A; Barral, Romina; Sherman, Ashley K; Miller, Elizabeth

    2016-02-01

    The purposes were to describe interest in hormonal contraception initiation among female adolescent in the emergency department (ED) and to assess for associations with factors known to increase pregnancy risk such as violence victimization. We used a computerized survey to assess sexual and dating practices, pregnancy history/likelihood, contraception use (including long-acting reversible contraception [LARC]) and concerns, contraception initiation interest, violence victimization, medical utilization, and demographics among sexually experienced females aged 14-19 years in our ED. The primary outcome was interest in contraception initiation. We compared responses between subgroups using the chi-square test. A total of 168 adolescents participated (82% of approached; mean age 16.6 years; 41% white; 48% black; 21% commercial insurance). Interest in contraception initiation was high: 60% overall and 70% among those not using hormonal contraception (n = 96). Among those using non-LARC contraception (n = 59), 29% were interested in LARC initiation. Contraception/LARC interest was positively associated with lack of recent well care (p contraception (p contraception at last intercourse. One third (36%) reported violence victimization. Most (70%) reported ≥1 concern about contraception (most commonly cost). Many reported behaviors and exposures, including violence victimization, that increase their risk for pregnancy and most expressed interest in same-day initiation of hormonal contraception, including LARC. These findings may inform novel strategies for increased adolescent access to contraception and pregnancy prevention through use of nontraditional sites such as EDs. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  15. Synthesis of Cassava Waste Pulp-Acrylamide Super Absorbent: Effect of Initiator and Cross-Linker Concentration

    Directory of Open Access Journals (Sweden)

    Zainal Alim Mas’ud

    2013-05-01

    Full Text Available Cassava waste pulp (CWP contains high carbohydrates that can be modified into super absorbent polymer (SAP through grafting and cross-linking copolymerization. Acrylamide (AM was grafted onto CWP with ammonium persulfate (APS as the initiator and N,N'-methylene-bis-acrylamide (MBA as the cross-linker under atmospheric nitrogen. The effect of APS and MBA concentrations on water absorption capacity of saponified SAP was studied, while the evaluation of grafting ratio (GR and grafting efficiency (GRE was conducted on unsaponified SAP. The grafting success was indicated by the occurrence of IR peaks at wave numbers of 573, 765, 858, and 1667 cm-1. In the saponified SAP, the very intense characteristic band at 1562 cm-1 is due to C=O asymmetric stretching in the carboxylate anion. Saponification increases significantly water absorption capacity compared to that of unsaponified SAP (from 39.79 g/g to 578.23 g/g. The highest water absorption capacity is reached at 0.74% APS and 0.09% MBA. The percentage of GRE and GR tends to increase with increasing APS concentration until reaching the highest value and then decreases. Effect of MBA concentration on water absorption capacity, GR, and on GRE is similar to the effect of initiator concentration on GR and GRE.

  16. Physical and functional interactions between Werner syndrome helicase and mismatch-repair initiation factors

    DEFF Research Database (Denmark)

    Saydam, Nurten; Kanagaraj, Radhakrishnan; Dietschy, Tobias

    2007-01-01

    is poorly understood. Here we show that WRN physically interacts with the MSH2/MSH6 (MutSalpha), MSH2/MSH3 (MutSbeta) and MLH1/PMS2 (MutLalpha) heterodimers that are involved in the initiation of mismatch repair (MMR) and the rejection of homeologous recombination. MutSalpha and MutSbeta can strongly......Werner syndrome (WS) is a severe recessive disorder characterized by premature aging, cancer predisposition and genomic instability. The gene mutated in WS encodes a bi-functional enzyme called WRN that acts as a RecQ-type DNA helicase and a 3'-5' exonuclease, but its exact role in DNA metabolism...... stimulate the helicase activity of WRN specifically on forked DNA structures with a 3'-single-stranded arm. The stimulatory effect of MutSalpha on WRN-mediated unwinding is enhanced by a G/T mismatch in the DNA duplex ahead of the fork. The MutLalpha protein known to bind to the MutS alpha...

  17. A 5' splice site enhances the recruitment of basal transcription initiation factors in vivo

    DEFF Research Database (Denmark)

    Damgaard, Christian Kroun; Kahns, Søren; Lykke-Andersen, Søren

    2008-01-01

    Transcription and pre-mRNA splicing are interdependent events. Although mechanisms governing the effects of transcription on splicing are becoming increasingly clear, the means by which splicing affects transcription remain elusive. Using cell lines stably expressing HIV-1 or β-globin mRNAs, harb...... a promoter-proximal 5′ splice site via its U1 snRNA interaction can feed back to stimulate transcription initiation by enhancing preinitiation complex assembly.......Transcription and pre-mRNA splicing are interdependent events. Although mechanisms governing the effects of transcription on splicing are becoming increasingly clear, the means by which splicing affects transcription remain elusive. Using cell lines stably expressing HIV-1 or β-globin mRNAs......, harboring wild-type or various 5′ splice site mutations, we demonstrate a strong positive correlation between splicing efficiency and transcription activity. Interestingly, a 5′ splice site can stimulate transcription even in the absence of splicing. Chromatin immunoprecipitation experiments show enhanced...

  18. Tendencies in human factor influence on initiating events occurrence in NPP Kozloduy

    International Nuclear Information System (INIS)

    Hristova, R.

    2001-01-01

    Overview of the methods and documents concerning human factor in nuclear safety and selection of the most appropriate methods and concept for human factor assessment in the reported events in Kozloduy NPP are presented. List of human error types and statistical data (the mean time between similar errors, the human rate λ, the number of occurrences ect.) is given. Some general results from the human error behavior investigation for all units of Kozloduy NPP related to the 4 personnel categories: Management personnel, Designers, Operating personnel, Maintenance personnel are also shown. At the end the following conclusion are made:18 % operating personnel errors (for comparison for the same category personnel in similar NPPs abroad this value is between 10 % and 30%); Human errors in Kozloduy NPP tend to increase after year 1990; only for the operating personnel a maximum near year 1997 was observed, after which the error values was decreased; at the beginning of year 2000 the reliability characteristics for all units have similar values; it is necessary to be taken into account the observed tendencies to take measurements for reducing of the most important error types for Kozloduy NPP personnel

  19. Anionic polymerization of acrylates. XIV. Synthesis of MMA/acrylate block copolymers initiated with ester-enolate/tert-alkoxide complex

    Czech Academy of Sciences Publication Activity Database

    Vlček, Petr; Čadová, Eva; Kříž, Jaroslav; Látalová, Petra; Janata, Miroslav; Toman, Luděk; Masař, Bohumil

    2005-01-01

    Roč. 46, č. 14 (2005), s. 4991-5000 ISSN 0032-3861 Institutional research plan: CEZ:AV0Z4050913 Keywords : ligated anionic polymerization * (meth)acrylates * block copolymers Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.849, year: 2005

  20. Acceptor-Substituted Ferrocenium Salts as Strong, Single-Electron Oxidants: Synthesis, Electrochemistry, Theoretical Investigations, and Initial Synthetic Application

    Czech Academy of Sciences Publication Activity Database

    Khobragade, Dushant; Mahamulkar, Shraddha G.; Pospíšil, Lubomír; Císařová, I.; Rulíšek, Lubomír; Jahn, Ullrich

    2012-01-01

    Roč. 18, č. 39 (2012), s. 12267-12277 ISSN 0947-6539 R&D Projects: GA ČR GA203/09/0705 Institutional support: RVO:61388963 Keywords : metallocenes * cyclic voltammetry * lactones * oxidation * redox chemistry Subject RIV: CC - Organic Chemistry Impact factor: 5.831, year: 2012

  1. Factors Affecting Initial Intimate Partner Violence-Specific Health Care Seeking in the Tokyo Metropolitan Area, Japan.

    Science.gov (United States)

    Kamimura, Akiko; Bybee, Deborah; Yoshihama, Mieko

    2014-09-01

    This study examined the factors affecting a women's initial intimate partner violence (IPV)-specific health care seeking event which refers to the first health care seeking as a result of IPV in a lifetime. Data were collected using the Life History Calendar method in the Tokyo metropolitan area from 101 women who had experienced IPV. Discrete-time survival analysis was used to assess the time to initial IPV-specific health care seeking. IPV-related injury was the most significant factor associated with increased likelihood of seeking IPV-specific health care seeking for the first time. In the presence of a strong effect of formal help seeking, physical and sexual IPV were no longer significantly related to initial IPV-specific health care seeking. The results suggest some victims of IPV may not seek health care unless they get injured. The timing of receiving health care would be important to ensure the health and safety of victims. © The Author(s) 2014.

  2. Factors Related to Initiating Interpersonal Contacts on Internet Dating Sites: A View From the Social Exchange Theory

    Directory of Open Access Journals (Sweden)

    Rivka Shtatfeld

    2009-12-01

    Full Text Available The purpose of this study was to identify factors that influence dating-site users to initiate contact with potential romantic partners. The study was carried out by observing online behaviors and analyzing the profiles and authentic messages of these users (N = 106 over seven months. Contacts made by and with the research participants were analyzed in terms of the relationships between initiators‘ and receivers‘ demographic variables (marital status, age, level of education, income, writing skills, and stated physical appearance. In addition, the relationship between contacting partners and site accessibility was examined. The findings revealed that dating-site users initiated contact primarily with those having a similar marital status or slightly better characteristics (income, education, writing skills. In regard to writing skills, it was found that skilled writers attracted more contacts than did less skilled writers. However, the factor that was found to be most significantly related to initiating contact was the length of time that elapsed from last connection to the site, which implies the perceived accessibility of potential romantic partners. The findings were explained in terms of the Social Exchange Theory: people are attracted to those who grant them rewards.

  3. Poly(glycidyl methacrylate) grafted CdSe quantum dots by surface-initiated atom transfer radical polymerization: Novel synthesis, characterization, properties, and cytotoxicity studies

    International Nuclear Information System (INIS)

    Bach, Long Giang; Islam, Md. Rafiqul; Lee, Doh Chang; Lim, Kwon Taek

    2013-01-01

    A novel approach for the synthesis of poly(glycidyl methacrylate) grafted CdSe quantum dot (QDs) (PGMA-g-CdSe) was developed. The PGMA-g-CdSe nanohybrids were synthesized by the surface-initiated atom transfer radical polymerization of glycidyl methacrylate from the surface of the strategic initiator, CdSe-BrIB QDs prepared by the interaction of 2-bromoisobutyryl bromide (BrIB) and CdSe-OH QDs. The structure, morphology, and optical property of the PGMA-g-CdSe nanohybrids were analyzed by FT-IR, XPS, TGA, XRD, TEM, and PL. The as-synthesized PGMA-g-CdSe nanohybrids having multi-epoxide groups were employed for the direct coupling of biotin via ring-opening reaction of the epoxide groups to afford the Biotin-f-PGMA-g-CdSe nanobioconjugate. The covalent immobilization of biotin onto PGMA-g-CdSe was confirmed by FT-IR, XPS, and EDX. Biocompatibility and imaging properties of the Biotin-f-PGMA-g-CdSe were investigated by MTT bioassay and PL analysis, respectively. The cell viability study suggested that the biocompatibility was significantly enhanced by the functionalization of CdSe QDs by biotin and PGMA.

  4. Expression and purification of Nod factor receptors - Initial characterization of ligand binding

    DEFF Research Database (Denmark)

    Broghammer, Angelique

    . Lipochitooligosaccharides also serve as signals in the mutually beneficial interactions between arbuscular mycorrhiza (AM) and most land plants. In the model legume Lotus japonicus the Nod factor receptors, LjNFR1 and LjNFR5, two LysM receptor like kinases (LysM-RLK), are responsible for perceiving the rhizobial...... and LjNFR5 ectodomains were glycosylated; 3) LjNFR1 retained its in vitro kinase activity and 4) LjNFR1 and LjNFR5 were localized to the plasma membrane. In depth mass spectroscopy analysis of the N-glycan structure of LjNFR5 resulted in identification of two different glycan structures with identical...

  5. Factors associated with the initiation of biologic disease-modifying antirheumatic drugs in Texas Medicaid patients with rheumatoid arthritis.

    Science.gov (United States)

    Kim, Gilwan; Barner, Jamie C; Rascati, Karen; Richards, Kristin

    2015-05-01

    Rheumatoid arthritis (RA) is a progressive autoimmune disorder of joints that is associated with high health care costs, yet guidance is lacking on how early to initiate biologic disease-modifying antirheumatic drugs (DMARDs), a class of medications that is the major cost driver in RA management. Few studies have examined the factors associated with the transition from nonbiologic DMARDs, the first-line therapy for RA, to biologic DMARDs in RA patients.  To examine patient sociodemographics, medication use patterns, and clinical characteristics associated with initiation of biologic DMARDs.   This was a retrospective study using the Texas Medicaid prescription and medical claims database from July 1, 2003-December 31, 2010. Adults (aged 18-63 years) with an RA diagnosis (ICD-9-CM code 714.xx), no nonbiologic DMARD or biologic DMARD use during the 6-month pre-index period, and a minimum of 2 prescription claims for the same nonbiologic DMARD during the post-index period were included in the study. The index date was defined as the date when the first nonbiologic DMARD claim was made. Predictors of initiation of biologic DMARDs were age, gender, race, adherence (proportion of days covered), persistence to nonbiologic DMARDs, comorbidity (Charlson Comorbidity Index [CCI]), pain medication use, glucocorticoid use, and rheumatologist visit. Logistic regression was used to examine the factors associated with the initiation of biologic DMARDs.   A total of 2,714 patients were included. After controlling for patient characteristics, logistic regression showed, that compared with methotrexate (MTX) users, sulfasalazine (SSZ) and hydroxychloroquine (HCQ) users were less likely to initiate biologic DMARDs by 69.0% (OR = 0.310, 95% CI = 0.221-0.434, P  less than  0.0001) and 79.9% (OR = 0.201, 95% CI = 0.152-0.265, P  less than  0.0001), respectively. Nonbiologic DMARD dual therapy users were 39.1% less likely to initiate biologic DMARDs compared

  6. Flavonoids Induce the Synthesis and Secretion of Neurotrophic Factors in Cultured Rat Astrocytes: A Signaling Response Mediated by Estrogen Receptor

    Directory of Open Access Journals (Sweden)

    Sherry L. Xu

    2013-01-01

    Full Text Available Neurotrophic factors are playing vital roles in survival, growth, and function of neurons. Regulation of neurotrophic factors in the brain has been considered as one of the targets in developing drug or therapy against neuronal disorders. Flavonoids, a family of multifunctional natural compounds, are well known for their neuronal beneficial effects. Here, the effects of flavonoids on regulating neurotrophic factors were analyzed in cultured rat astrocytes. Astrocyte is a major secreting source of neurotrophic factors in the brain. Thirty-three flavonoids were screened in the cultures, and calycosin, isorhamnetin, luteolin, and genistein were identified to be highly active in inducing the synthesis and secretion of neurotrophic factors, including nerve growth factor (NGF, glial-derived neurotrophic factor (GDNF, and brain-derived neurotrophic factor (BDNF. The inductions were in time- and dose-dependent manners. In cultured astrocytes, the phosphorylation of estrogen receptor was triggered by application of flavonoids. The phosphorylation was blocked by an inhibitor of estrogen receptor, which in parallel reduced the flavonoid-induced expression of neurotrophic factors. The results proposed the role of flavonoids in protecting brain diseases, and therefore these flavonoids could be developed for health food supplement for patients suffering from neurodegenerative diseases.

  7. Intervening factors for the initiation of treatment of patients with stomach and colorectal cancer.

    Science.gov (United States)

    Valle, Thaína Dalla; Turrini, Ruth Natalia Teresa; Poveda, Vanessa de Brito

    2017-05-15

    to identify the time between symptoms, the request for care and the beginning of treatment in patients with stomach and colorectal cancer as well as the factors that interfere in these processes. correlational descriptive study, including 101 patients diagnosed with stomach or colorectal cancer, treated in a hospital specialized in oncology. the 101 patients investigated there was predominance of males, mean age of 61.7 years. The search for medical care occurred within 30 days after the onset of symptoms, in most cases. The mean total time between the onset of symptoms and the beginning of treatment ranged from 15 to 16 months, and the mean time between the search for medical care and the diagnosis was 4.78 months. The family history of cancer (p=0.008) and the implementation of preventive follow-up (pel tiempo entre los síntomas, la búsqueda de asistencia y el inicio del tratamiento en pacientes con cáncer gástrico y colorrectal y los factores que interfieren en estos procesos. estudio descriptivo correlacional, incluyendo 101 pacientes con diagnostico de cáncer gástrico o colorrectal, atendidos en un hospital especializado en oncología. de 101 pacientes investigados la mayoria eran hombres, con edad media de 61,7 años. La búsqueda de la atención médica se produjo dentro de los 30 días después de la aparición de los síntomas, en la mayoría de los casos. El promedio de tiempo total entre el inicio de los síntomas y el inicio del tratamiento fue de 15,16 meses y el tiempo medio entre la búsqueda de la atención médica y el diagnóstico fue de 4,78 meses. La historia familiar de cáncer (p=0,008) y la realización de seguimiento preventivo (pel tratamiento temprano. Náuseas, vómitos, hematoquecia, pérdida de peso y dolor se asociaron con la búsqueda más rápida de la asistencia. el intervalo más largo entre la búsqueda de la atención médica y el diagnóstico se produjo posiblemente por asociación negativa entre los síntomas que se

  8. Hypoxia-inducing factors as master regulators of stemness properties and altered metabolism of cancer- and metastasis-initiating cells

    Science.gov (United States)

    Mimeault, Murielle; Batra, Surinder K

    2013-01-01

    Accumulating lines of experimental evidence have revealed that hypoxia-inducible factors, HIF-1α and HIF-2α, are key regulators of the adaptation of cancer- and metastasis-initiating cells and their differentiated progenies to oxygen and nutrient deprivation during cancer progression under normoxic and hypoxic conditions. Particularly, the sustained stimulation of epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), stem cell factor (SCF) receptor KIT, transforming growth factor-β receptors (TGF-βRs) and Notch and their downstream signalling elements such as phosphatidylinositol 3′-kinase (PI3K)/Akt/molecular target of rapamycin (mTOR) may lead to an enhanced activity of HIFs. Moreover, the up-regulation of HIFs in cancer cells may also occur in the hypoxic intratumoral regions formed within primary and secondary neoplasms as well as in leukaemic cells and metastatic prostate and breast cancer cells homing in the hypoxic endosteal niche of bone marrow. The activated HIFs may induce the expression of numerous gene products such as induced pluripotency-associated transcription factors (Oct-3/4, Nanog and Sox-2), glycolysis- and epithelial-mesenchymal transition (EMT) programme-associated molecules, including CXC chemokine receptor 4 (CXCR4), snail and twist, microRNAs and angiogenic factors such as vascular endothelial growth factor (VEGF). These gene products in turn can play critical roles for high self-renewal ability, survival, altered energy metabolism, invasion and metastases of cancer cells, angiogenic switch and treatment resistance. Consequently, the targeting of HIF signalling network and altered metabolic pathways represents new promising strategies to eradicate the total mass of cancer cells and improve the efficacy of current therapies against aggressive and metastatic cancers and prevent disease relapse. PMID:23301832

  9. Physical and functional interactions between Werner syndrome helicase and mismatch-repair initiation factors

    DEFF Research Database (Denmark)

    Saydam, Nurten; Kanagaraj, Radhakrishnan; Dietschy, Tobias

    2007-01-01

    Werner syndrome (WS) is a severe recessive disorder characterized by premature aging, cancer predisposition and genomic instability. The gene mutated in WS encodes a bi-functional enzyme called WRN that acts as a RecQ-type DNA helicase and a 3'-5' exonuclease, but its exact role in DNA metabolism...... stimulate the helicase activity of WRN specifically on forked DNA structures with a 3'-single-stranded arm. The stimulatory effect of MutSalpha on WRN-mediated unwinding is enhanced by a G/T mismatch in the DNA duplex ahead of the fork. The MutLalpha protein known to bind to the MutS alpha......-heteroduplex complexes has no effect on WRN-mediated DNA unwinding stimulated by MutSalpha, nor does it affect DNA unwinding by WRN alone. Our data are consistent with results of genetic experiments in yeast suggesting that MMR factors act in conjunction with a RecQ-type helicase to reject recombination between...

  10. Polysomes of Trypanosoma brucei: Association with Initiation Factors and RNA-Binding Proteins.

    Directory of Open Access Journals (Sweden)

    Cornelia Klein

    Full Text Available We report here the results of experiments designed to identify RNA-binding proteins that might be associated with Trypanosoma brucei polysomes. After some preliminary mass spectrometry of polysomal fractions, we investigated the distributions of selected tagged proteins using sucrose gradients and immunofluorescence. As expected, the polysomal fractions contained nearly all annotated ribosomal proteins, the translation-associated protein folding complex, and many translation factors, but also many other abundant proteins. Results suggested that cap-binding proteins EIF4E3 and EIF4E4 were associated with both free and membrane-bound polysomes. The EIF4E binding partners EIF4G4 and EIF4G3 were present but the other EIF4E and EIF4G paralogues were not detected. The dominant EIF4E in the polysomal fraction is EIF4E4 and very few polysomal mRNAs are associated with EIF4G. Thirteen potential mRNA-binding proteins were detected in the polysomes, including the known polysome-associated protein RBP42. The locations of two of the other proteins were tested after epitope tagging: RBP29 was in the nucleus and ZC3H29 was in the cytoplasm. Quantitative analyses showed that specific association of an RNA-binding protein with the polysome fraction in sucrose gradients will not be detected if the protein is in more than 25-fold molar excess over its target binding sites.

  11. Initial investigation of organisational factors associated with the implementation of active support.

    Science.gov (United States)

    Fyffe, Chris; McCubbery, Jeffrey; Reid, Katharine J

    2008-09-01

    Active support (AS) has been shown to increase the amount of time that residents in shared residential settings are involved in purposeful activities. The organisational processes required to implement AS have been less well researched. Staff in community houses answered questions about the occurrence of organisational activities and processes thought to assist AS implementation (e.g., training and teamwork), their understanding of engagement, and their experience of changes in staff practice consistent with AS (including implementation problems). Non-house-based managers were also interviewed about their role in AS implementation. Reported occurrence of organisational activities and processes (e.g., training and teamwork) and understanding of engagement were associated with more reports of changes in staff practice and fewer staff reports of implementation problems. Staff reports on the role of non-house-based managers were not associated with reports of changes in staff practice or with reports of fewer AS implementation problems. Non-house-based managers' reports overestimated their role in AS implementation when compared with reports from house-based staff groups. While there are limitations in the research design (including the reliance on staff reports), the findings support the importance of wider organisational factors (beyond training programs for direct support staff) as integral to the implementation of AS. There is a need for further research on AS implementation.

  12. Intervening factors for the initiation of treatment of patients with stomach and colorectal cancer

    Directory of Open Access Journals (Sweden)

    Thaína Dalla Valle

    Full Text Available ABSTRACT Objective: to identify the time between symptoms, the request for care and the beginning of treatment in patients with stomach and colorectal cancer as well as the factors that interfere in these processes. Method: correlational descriptive study, including 101 patients diagnosed with stomach or colorectal cancer, treated in a hospital specialized in oncology. Results: the 101 patients investigated there was predominance of males, mean age of 61.7 years. The search for medical care occurred within 30 days after the onset of symptoms, in most cases. The mean total time between the onset of symptoms and the beginning of treatment ranged from 15 to 16 months, and the mean time between the search for medical care and the diagnosis was 4.78 months. The family history of cancer (p=0.008 and the implementation of preventive follow-up (p<0.001 were associated with shorter periods between the search for care and the beginning of treatment. Nausea, vomiting, hematochezia, weight loss and pain were associated with faster demand for care. Conclusion: the longer interval between the search for medical care and the diagnosis was possibly due to the non-association between the presented symptoms and the disease.

  13. Factors associated with initial or subsequent choice of biologic disease-modifying antirheumatic drugs for treatment of rheumatoid arthritis.

    Science.gov (United States)

    Jin, Yinzhu; Desai, Rishi J; Liu, Jun; Choi, Nam-Kyong; Kim, Seoyoung C

    2017-07-05

    Biologic disease-modifying antirheumatic drugs (DMARDs) are increasingly used for rheumatoid arthritis (RA) treatment. However, little is known based on contemporary data about the factors associated with DMARDs and patterns of use of biologic DMARDs for initial and subsequent RA treatment. We conducted an observational cohort study using claims data from a commercial health plan (2004-2013) and Medicaid (2000-2010) in three study groups: patients with early untreated RA who were naïve to any type of DMARD and patients with prevalent RA with or without prior exposure to one biologic DMARD. Multivariable logistic regression models were used to examine the effect of patient demographics, clinical characteristics and healthcare utilization factors on the initial and subsequent choice of biologic DMARDs for RA. We identified a total of 195,433 RA patients including 78,667 (40%) with early untreated RA and 93,534 (48%) and 23,232 (12%) with prevalent RA, without or with prior biologic DMARD treatment, respectively. Patients in the commercial insurance were 87% more likely to initiate a biologic DMARD versus patients in Medicaid (OR = 1.87, 95% CI = 1.70-2.05). In Medicaid, African-Americans had lower odds of initiating (OR = 0.59, 95% CI = 0.51-0.68 in early untreated RA; OR = 0.71, 95% CI = 0.61-0.74 in prevalent RA) and switching (OR = 0.71, 95% CI = 0.55-0.90) biologic DMARDs than non-Hispanic whites. Prior use of steroid and non-biologic DMARDs predicted both biologic DMARD initiation and subsequent switching. Etanercept, adalimumab, and infliximab were the most commonly used first-line and second-line biologic DMARDS; patients on anakinra and golimumab were most likely to be switched to other biologic DMARDS. Insurance type, race, and previous use of steroids and non-biologic DMARDs were strongly associated with initial or subsequent treatment with biologic DMARDs.

  14. Fatores determinantes para modificações da terapia antirretroviral inicial Factors determining changes in initial antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Denise Girão Limaverde Lima

    2012-04-01

    Full Text Available OBJETIVO: Investigar os fatores determinantes das mudanças da terapia antirretroviral (TARV inicial dos pacientes assistidos em hospital de referência em AIDS do Ceará. MÉTODOS: O estudo descritivo e exploratório utilizou a análise dos formulários de solicitação de início ou modificação de tratamento do ano de 2008, acompanhando as mudanças de terapia durante o primeiro ano de tratamento. Os dados foram analisados nos programas Statistical Package for the Social Sciences (SPSS e Epi Info, utilizando ANOVA e teste exato do coeficiente de contingência, com significância de p OBJECTIVE: To investigate factors determining changes in initial antiretroviral therapy (ART in patients attended to in an AIDS tertiary care hospital in Ceará, Brazil. METHODS: This descriptive and exploratory study used the analysis of request to initiate or change treatment forms in the year of 2008, and the changes in therapy were followed through the first year of treatment. Data were analyzed with SPSS and EpiInfo by using ANOVA and the exact test of the coefficient of contingency, with significance at p < 0.05. RESULTS: From 301 patients initiating ART, 22.1% (n = 68 needed a change in the first year. These patients were mostly males, aged 20 to 39 years; with only one ART changed needed in 86.8% of the cases (n = 59. Reports of two or three changes in regimen were observed. Zidovudine was the drug most often changed, followed by lopinavir/ritonavir and efavirenz. A significant association was found between changes in initial regimens and the report of adverse reactions (p < 0.001. Conclusion: The main factor determining changes in the initial ART was an adverse reaction report. Most patients had one change in the initial ART over the first year of treatment. ART monitoring contributed to a better control of the specific drug therapy.

  15. Do Maternal Caregiver Perceptions of Childhood Obesity Risk Factors and Obesity Complications Predict Support for Prevention Initiatives Among African Americans?

    Science.gov (United States)

    Alexander, Dayna S; Alfonso, Moya L; Cao, Chunhua; Wright, Alesha R

    2017-07-01

    Objectives African American maternal caregiver support for prevention of childhood obesity may be a factor in implementing, monitoring, and sustaining children's positive health behaviors. However, little is known about how perceptions of childhood obesity risk factors and health complications influence caregivers' support of childhood obesity prevention strategies. The objective of this study was to determine if childhood obesity risk factors and health complications were associated with maternal caregivers' support for prevention initiatives. Methods A convenience sample of maternal caregivers (N = 129, ages 22-65 years) completed the childhood obesity perceptions (COP) survey. A linear regression was conducted to determine whether perceptions about childhood obesity risk factors and subsequent health complications influenced caregivers' support for prevention strategies. Results Caregivers' perceptions of childhood obesity risk factors were moderate (M = 3.4; SD = 0.64), as were their perceptions of obesity-related health complications (M = 3.3; SD = 0.75); however, they perceived a high level of support for prevention strategies (M = 4.2; SD = 0.74). In the regression model, only health complications were significantly associated with caregiver support (β = 0.348; p Childhood obesity prevention efforts should emphasize health complications by providing education and strategies that promote self-efficacy and outcome expectations among maternal caregivers.

  16. Diminishing friction of joint surfaces as initiating factor for destabilising permafrost rocks?

    Science.gov (United States)

    Funk, Daniel; Krautblatter, Michael

    2010-05-01

    Degrading alpine permafrost due to changing climate conditions causes instabilities in steep rock slopes. Due to a lack in process understanding, the hazard is still difficult to asses in terms of its timing, location, magnitude and frequency. Current research is focused on ice within joints which is considered to be the key-factor. Monitoring of permafrost-induced rock failure comprises monitoring of temperature and moisture in rock-joints. The effect of low temperatures on the strength of intact rock and its mechanical relevance for shear strength has not been considered yet. But this effect is signifcant since compressive and tensile strength is reduced by up to 50% and more when rock thaws (Mellor, 1973). We hypotheisze, that the thawing of permafrost in rocks reduces the shear strength of joints by facilitating the shearing/damaging of asperities due to the drop of the compressive/tensile strength of rock. We think, that decreasing surface friction, a neglected factor in stability analysis, is crucial for the onset of destabilisation of permafrost rocks. A potential rock slide within the permafrost zone in the Wetterstein Mountains (Zugspitze, Germany) is the basis for the data we use for the empirical joint model of Barton (1973) to estimate the peak shear strength of the shear plane. Parameters are the JRC (joint roughness coefficient), the JCS (joint compressive strength) and the residual friction angle (φr). The surface roughness is measured in the field with a profile gauge to create 2D-profiles of joint surfaces. Samples of rock were taken to the laboratory to measure compressive strength using a high-impact Schmidt-Hammer under air-dry, saturated and frozen conditions on weathered and unweathered surfaces. Plugs where cut out of the rock and sand blasted for shear tests under frozen and unfrozen conditions. Peak shear strength of frozen and unfrozen rocks will be calculated using Barton's model. First results show a mean decrease of compressive

  17. Members of the LBD family of transcription factors repress anthocyanin synthesis and affect additional nitrogen responses in Arabidopsis.

    Science.gov (United States)

    Rubin, Grit; Tohge, Takayuki; Matsuda, Fumio; Saito, Kazuki; Scheible, Wolf-Rüdiger

    2009-11-01

    Nitrogen (N) and nitrate (NO(3)(-)) per se regulate many aspects of plant metabolism, growth, and development. N/NO(3)(-) also suppresses parts of secondary metabolism, including anthocyanin synthesis. Molecular components for this repression are unknown. We report that three N/NO(3)(-)-induced members of the LATERAL ORGAN BOUNDARY DOMAIN (LBD) gene family of transcription factors (LBD37, LBD38, and LBD39) act as negative regulators of anthocyanin biosynthesis in Arabidopsis thaliana. Overexpression of each of the three genes in the absence of N/NO(3)(-) strongly suppresses the key regulators of anthocyanin synthesis PAP1 and PAP2, genes in the anthocyanin-specific part of flavonoid synthesis, as well as cyanidin- but not quercetin- or kaempferol-glycoside production. Conversely, lbd37, lbd38, or lbd39 mutants accumulate anthocyanins when grown in N/NO(3)(-)-sufficient conditions and show constitutive expression of anthocyanin biosynthetic genes. The LBD genes also repress many other known N-responsive genes, including key genes required for NO(3)(-) uptake and assimilation, resulting in altered NO(3)(-) content, nitrate reductase activity/activation, protein, amino acid, and starch levels, and N-related growth phenotypes. The results identify LBD37 and its two close homologs as novel repressors of anthocyanin biosynthesis and N availability signals in general. They also show that, besides being developmental regulators, LBD genes fulfill roles in metabolic regulation.

  18. Effects of Psychological and Social Work Factors on Self-Reported Sleep Disturbance and Difficulties Initiating Sleep.

    Science.gov (United States)

    Vleeshouwers, Jolien; Knardahl, Stein; Christensen, Jan Olav

    2016-04-01

    This prospective cohort study examined previously underexplored relations between psychological/social work factors and troubled sleep in order to provide practical information about specific, modifiable factors at work. A comprehensive evaluation of a range of psychological/social work factors was obtained by several designs; i.e., cross-sectional analyses at baseline and follow-up, prospective analyses with baseline predictors (T1), prospective analyses with average exposure across waves as predictor ([T1 + T2] / 2), and prospective analyses with change in exposure from baseline to follow-up as predictor. Participants consisted of a sample of Norwegian employees from a broad spectrum of occupations, who completed a questionnaire at two points in time, approximately two years apart. Cross-sectional analyses at T1 comprised 7,459 participants, cross-sectional analyses at T2 included 6,688 participants. Prospective analyses comprised a sample 5,070 of participants who responded at both T1 and T2. Univariable and multivariable ordinal logistic regressions were performed. Thirteen psychological/social work factors and two aspects of troubled sleep, namely difficulties initiating sleep and disturbed sleep, were studied. Ordinal logistic regressions revealed statistically significant associations for all psychological and social work factors in at least one of the analyses. Psychological and social work factors predicted sleep problems in the short term as well as the long term. All work factors investigated showed statistically significant associations with both sleep items, however quantitative job demands, decision control, role conflict, and support from superior were the most robust predictors and may therefore be suitable targets of interventions aimed at improving employee sleep. © 2016 Associated Professional Sleep Societies, LLC.

  19. Factors influencing the implementation of fall-prevention programmes: a systematic review and synthesis of qualitative studies

    Directory of Open Access Journals (Sweden)

    Child Sue

    2012-09-01

    Full Text Available Abstract Background More than a third of people over the age of 65 years fall each year. Falling can lead to a reduction in quality of life, mortality, and a risk of prolonged hospitalisation. Reducing and preventing falls has become an international health priority. To help understand why research evidence has often not been translated into changes in clinical practice, we undertook a systematic review and synthesis of qualitative research in order to identify what factors serve as barriers and facilitators to the successful implementation of fall-prevention programmes. Methods We conducted a review of literature published between 1980 and January 2012 for qualitative research studies that examined barriers and facilitators to the effective implementation of fall-prevention interventions among community-dwelling older people and healthcare professionals. Two reviewers independently screened studies for inclusion, extracted data, and assessed methodological quality according to predefined criteria. Findings were synthesised using meta-ethnography. Results Of the 5010 articles identified through database searching, 19 were included in the review. Analysis of the 19 studies revealed limited information about the mechanisms by which barriers to implementation of fall-prevention interventions had been overcome. Data synthesis produced three overarching concepts: (1 practical considerations, (2 adapting for community, and (3 psychosocial. A line of argument synthesis describes the barriers and facilitators to the successful implementation of fall-prevention programmes. These concepts show that the implementation of fall-prevention programmes is complex and multifactorial. This is the first systematic review and synthesis of qualitative studies to examine factors influencing the implementation of fall-prevention programmes from the perspectives of both the healthcare professional and the community-dwelling older person. Conclusions The current

  20. Initial Segment Differentiation Begins During a Critical Window and Is Dependent upon Lumicrine Factors and SRC Proto-Oncogene (SRC) in the Mouse.

    Science.gov (United States)

    Xu, Bingfang; Washington, Angela M; Hinton, Barry T

    2016-07-01

    Without a fully developed and functioning initial segment, the most proximal region of the epididymis, male infertility results. Therefore, it is important to understand the development of the initial segment. During postnatal development of the epididymis, many cellular processes of the initial segment are regulated by lumicrine factors, which are produced by the testis and enter the epididymis with testicular luminal fluid. In this report, we showed that prior to Postnatal Day 15 (P15), the initial segment was lumicrine factor independent in the mouse. However, from P19 onward, lumicrine factors were essential for the proliferation and survival of initial segment epithelial cells. Therefore, P15 to P19 was a critical window that established the dependency of lumicrine factors in the initial segment epithelium. The initial segment-specific kinase activity profile, a marker of initial segment differentiation, was also established during this window. The SFK (SRC proto-oncogene family kinases), ERK pathway (known as the RAF/MEK/ERK pathway) components, and AMPK (AMP-activated protein kinases) pathway components had increased activities from P15 to P19, suggesting that lumicrine factors regulated SFK/ERK/AMPK signaling to initiate differentiation of the initial segment from P15 to P19. Compared with litter mate controls, juvenile Src null mice displayed lower levels of MAPK3/1 (mitogen-activated protein kinase 3/1) activity and a reduced level of differentiation in the initial segment epithelium, a similar phenotype resulting from inhibition of SRC activity within the window of P15 to P19. Therefore, lumicrine factor-dependent SRC activity signaling through MAPK3/1 is important for the initiation of initial segment differentiation during a critical window of development. © 2016 by the Society for the Study of Reproduction, Inc.

  1. Factors influencing adolescent girls' decision in initiation for human papillomavirus vaccination: a cross-sectional study in Hong Kong.

    Science.gov (United States)

    Lee, Albert; Ho, Mandy; Cheung, Calvin Ka Man; Keung, Vera Mei Wen

    2014-09-08

    Cervical cancer is one of the common cancers among women worldwide. Despite HPV vaccination being one of the effective preventive measures, it is not included in government vaccination programme in Hong Kong. This study aimed to assess the knowledge of and attitude towards cervical cancer prevention among Chinese adolescent girls in Hong Kong, and to identify factors influencing the initiation of HPV vaccination. This was a cross-sectional study conducted in Hong Kong during the period of October 2010 to November 2010. A self-administered questionnaire was used, with 1,416 girls from 8 secondary schools completing the questionnaire. Knowledge scores were composited and initiation of HPV vaccination was staged based on stage of change. Analyses were conducted to identify the association of initiation of HPV vaccination with participant's personal and family factors as well as their knowledge and attitude towards cervical cancer prevention. The uptake rate of HPV vaccination was low (7%) with 58% respondents in pre-contemplation and contemplation stage. The survey identified a significant gap in knowledge on cervical cancer prevention. The main channels of information were from media and very few from schools or parents. However, 70% expressed their wishes to have more information on cancer prevention, and 78% stated that they were willing to change their lifestyles if they knew the ways of prevention. Multivariate analysis identified three independent significant factors for initiation of vaccination (action and intention): perceived cancer as terrifying disease, school should provide more information on cancer prevention, and comments from relatives and friends having received the vaccine. The cost of vaccination and socio-economic background were not found to be significant. Public education on cervical cancer needs to be well penetrated into the community for more sharing among friends and relatives. School as setting to provide source of information would

  2. [Relationship between the resuscitation promoting role of resuscitation promoting factor and the initial bacteria amount of dormant Mycobacterium tuberculosis].

    Science.gov (United States)

    Liu, Zhong-Quan; Xing, Ai-Ying; Gu, Shu-Xiang; Jia, Hong-Yan; Zhang, Zong-De

    2009-08-01

    To investigate the relationship between the resuscitation promoting role of resuscitation promoting factor and the initial bacteria amount of dormant Mycobacterium tuberculosis. Mycobacterium tuberculosis (dormant bacteria) was cultured for 100 days, then diluted into 1 mg/ml concentration with 7H9, and further diluted into 0.5, 0.25, 0.125, 0.0625, and 0.03125 mg/ml. Twelve new tubes added with 5 ml 7H9 and divided into two groups: the first group was added with the resuscitation-promoting factor protein, and the second group as control was added with 7H9. In each group the above diluted solutions were added. The tubes were located at 37 degrees C for culture. Optical density (OD) was detected on day 15, 25, 30, and 35. From each tube 1 microl culture solution was plated on 7H11 medium for colony counting. OD detection showed that bacteria proliferation in each group had positive linear correlation (P dormant Mycobacterium tuberculosis and its initial bacteria amount.

  3. A comparative study of historical droughts over Texas, USA and Murray-Darling Basin, Australia: Factors influencing initialization and cessation

    Science.gov (United States)

    Verdon-Kidd, Danielle C.; Scanlon, Bridget R.; Ren, Tong; Fernando, D. Nelun

    2017-02-01

    Water availability and food security are tightly coupled on a global scale. The occurrence of drought puts this balance at risk due to reductions in dryland farming production and water allocations to irrigated agriculture. Improved understanding of drought initiation and cessation would therefore be beneficial for drought planning and management. The study objective was to determine factors affecting drought initiation and cessation over the past century in two climatologically similar regions that represent net agricultural exporters; south central U.S. (Texas) and southeast Australia (Murray Darling Basin, MDB). Drought indices included the Standardized Precipitation Index (SPI, 1900-2014) for meteorological drought, the Normalized Difference Vegetation Index (NDVI, 1981-2014) for agricultural drought, and the Streamflow Drought Index (SDI, 1930-2014) for hydrological drought. Results show that meteorological drought tends to develop gradually over a period of up to six months, with agricultural drought developing shortly thereafter (within one month) in both regions. Evidence of hydrological drought was observed within one month (Texas) and within four months (MDB) on average after meteorological drought was established. Further, droughts appear to cease more quickly than they initiate over Texas, whereas rates of drought initiation and cessation are similar over the MDB. Drought breaking rainfall in Texas is generally a result of a southward shift in the Polar Jet Stream or a low-pressure trough over central North America, whereas drought cessation in the MDB is typically associated with a monsoon trough or low-pressure system in the Tasman Sea/Great Australian Bight. Improved knowledge of the climate mechanisms controlling the onset and termination of drought periods should enhance drought forecasts and improve drought management practices, particularly in regions where water security is a primary objective.

  4. Factors affecting the initial adhesion and retention of the plant pathogen Xylella fastidiosa in the foregut of an insect vector.

    Science.gov (United States)

    Killiny, Nabil; Almeida, Rodrigo P P

    2014-01-01

    Vector transmission of bacterial plant pathogens involves three steps: pathogen acquisition from an infected host, retention within the vector, and inoculation of cells into susceptible tissue of an uninfected plant. In this study, a combination of plant and artificial diet systems were used to determine the importance of several genes on the initial adhesion and retention of the bacterium Xylella fastidiosa to an efficient insect vector. Mutant strains included fimbrial (fimA and pilB) and afimbrial (hxfA and hxfB) adhesins and three loci involved in regulatory systems (rpfF, rpfC, and cgsA). Transmission assays with variable retention time indicated that HxfA and HxfB were primarily important for early adhesion to vectors, while FimA was necessary for both adhesion and retention. The long pilus protein PilB was not deficient in initial adhesion but may be important for retention. Genes upregulated under the control of rpfF are important for both initial adhesion and retention, as transmission rates of this mutant strain were initially low and decreased over time, while disruption of rpfC and cgsA yielded trends similar to that shown by the wild-type control. Because induction of an X. fastidiosa transmissible state requires pectin, a series of experiments were used to test the roles of a polygalacturonase (pglA) and the pectin and galacturonic acid carbohydrates on the transmission of X. fastidiosa. Results show that galacturonic acid, or PglA activity breaking pectin into its major subunit (galacturonic acid), is required for X. fastidiosa vector transmission using an artificial diet system. This study shows that early adhesion and retention of X. fastidiosa are mediated by different factors. It also illustrates that the interpretation of results of vector transmission experiments, in the context of vector-pathogen interaction studies, is highly dependent on experimental design.

  5. A Prospective Study on the Influence of Scholastic Factors on the Prevalence and Initiation of Illicit Drug Misuse in Adolescence.

    Science.gov (United States)

    Zubak, Zoran; Zenic, Natasa; Ostojic, Ljerka; Zubak, Ivana; Pojskic, Haris

    2018-04-27

    This study aimed to prospectively investigate the scholastic factors related to illicit drug misuse (IDM) and the initiation of IDM among older adolescents from Bosnia and Herzegovina. This 2-year prospective study included 436 participants (202 females), who were an average of 16 years old at the beginning of the study (baseline). The participants were tested at baseline and follow-up (20 months later). The predictors included variables of scholastic-achievement (grade point average, school absences, unexcused absences and behavioral grade). The criteria were: (i) IDM at baseline; (ii) IDM at follow-up; and (iii) initiation of IDM over the study course. Results : Logistic regression indicated increased odds of IDM in adolescents who were more frequent absent from school (baseline: Odds Ratio (OR): 3.73, 95% Confidence Interval (CI): 2.12⁻6.57; follow-up: OR: 2.91, 95% CI: 1.90⁻4.65). The lower grade point average and more unexcused absences were evidenced for adolescents who consumed drugs on follow-up (OR: 1.67, 95% CI: 1.11⁻2.51; OR: 1.74, 95% CI: 1.30⁻2.32 for grade point average and unexcused absences, respectively). Initiation of IDM was predicted by frequent absences from school (OR: 2.2, 95% CI: 1.3⁻3.8), and lower behavioral grades (OR: 1.9, 95% CI: 1.2⁻3.3). The findings confirmed strong correlations between scholastic failure and IDM. Absences from school and lower behavioral grades at baseline were predictive of the initiation of IDM in older adolescents.

  6. Transitioning organic synthesis from organic solvents to water. What's your E Factor?

    Science.gov (United States)

    Lipshutz, Bruce H.; Ghorai, Subir

    2014-01-01

    Traditional organic chemistry, and organic synthesis in particular, relies heavily on organic solvents, as most reactions involve organic substrates and catalysts that tend to be water-insoluble. Unfortunately, organic solvents make up most of the organic waste created by the chemical enterprise, whether from academic, industrial, or governmental labs. One alternative to organic solvents follows the lead of Nature: water. To circumvent the solubility issues, newly engineered “designer” surfactants offer an opportunity to efficiently enable many of the commonly used transition metal-catalyzed and related reactions in organic synthesis to be run in water, and usually at ambient temperatures. This review focuses on recent progress in this area, where such amphiphiles spontaneously self-aggregate in water. The resulting micellar arrays serve as nanoreactors, obviating organic solvents as the reaction medium, while maximizing environmental benefits. PMID:25170307

  7. Transforming growth factor-beta, but not ciliary neurotrophic factor, inhibits DNA synthesis of adrenal medullary cells in vitro

    DEFF Research Database (Denmark)

    Wolf, N; Krohn, K; Bieger, S

    1999-01-01

    by the neuroendocrine chromaffin cells, which also express the transforming growth factor-beta receptor type II. In contrast to the developmentally related sympathetic neurons, chromaffin cells continue to proliferate throughout postnatal life. Using 5-bromo-2'-deoxyuridine pulse labeling and tyrosine hydroxylase......Transforming growth factor-betas are members of a superfamily of multifunctional cytokines regulating cell growth and differentiation. Their functions in neural and endocrine cells are not well understood. We show here that transforming growth factor-betas are synthesized, stored and released...... immunocytochemistry as a marker for young postnatal rat chromaffin cells, we show that treatment with fibroblast growth factor-2 (1 nM) and insulin-like growth factor-II (10 nM) increased the fraction of 5-bromo-2'-deoxyuridine-labeled nuclei from 1% to about 40% of the cells in the absence of serum. In the presence...

  8. Increase in tendon protein synthesis in response to insulin-like growth factor-I is preserved in elderly men

    DEFF Research Database (Denmark)

    Nielsen, Rie Harboe; Holm, Lars; Malmgaard-Clausen, Nikolaj Mølkjær

    2014-01-01

    Insulin-like growth factor-I (IGF-I) is known to be an anabolic factor in tendon, and the systemic levels are reduced with aging. However, it is uncertain how tendon fibroblasts are involved in tendon aging and how aging cells respond to IGF-I. The purpose of this study was to investigate...... the in vivo IGF-I stimulation of tendon protein synthesis in elderly compared with young men. We injected IGF-I in the patellar tendons of young (n = 11, 20-30 yr of age) and old (n = 11, 66-75 yr of age) men, and the acute fractional synthesis rate (FSR) of tendon protein was measured with the stable isotope...... technique and compared with the contralateral side (injected with saline as control). We found that tendons injected with IGF-I had significantly higher protein FSR compared with controls (old group: 0.018 ± 0.015 vs. 0.008 ± 0.008, young group: 0.016 ± 0.009 vs. 0.009 ± 0.006%/h, mean ± SE, P

  9. Role of Protein Synthesis Initiation Factors in Dietary Soy Isoflavone-Mediated Effects on Breast Cancer Progression

    Science.gov (United States)

    2014-08-01

    of postmenopausal Malay women consuming tempeh compared with milk , Int.J.Food Sci.Nutr., 62: 642-650, 2011. 14 26 Meyer,N. and Penn,L.Z...Higher bioavailability of isoflavones after a single ingestion of aglycone-rich fermented soybeans compared with glucoside-rich non- fermented ...bioavailability of isoflavones in urinary excretions of postmenopausal Malay women consuming tempeh compared with milk , Int.J.Food Sci.Nutr., 62: 642

  10. Role of Protein Synthesis Initiation Factors in Dietary Soy Isoflavone-Mediated Effects on Breast Cancer Progression

    Science.gov (United States)

    2012-03-01

    W81XWH-11-1-0199 Abstract on next page. Subject terms on next page. 54 1 MAR 2011 - 28 FEB 2012Annual Summary01-03-2012 columba.delaparra@upr.edu 2...Montemayor2, Surangani F. Dharmawardhane Flanagan1. 1Univ. of Puerto Rico Med. Science Campus, San Juan, PR; 2Universidad Central del Caribe , Bayamon...Dharmawardhane Flanagan1. 1Univ. of Puerto Rico Med. Science Campus, San Juan, PR; 2Universidad Central del Caribe , Bayamon, PR 11

  11. Gefitinib and Erlotinib Lead to Phosphorylation of Eukaryotic Initiation Factor 2 Alpha Independent of Epidermal Growth Factor Receptor in A549 Cells.

    Science.gov (United States)

    Koyama, Satoshi; Omura, Tomohiro; Yonezawa, Atsushi; Imai, Satoshi; Nakagawa, Shunsaku; Nakagawa, Takayuki; Yano, Ikuko; Matsubara, Kazuo

    2015-01-01

    Gefitinib and erlotinib are anticancer agents, which inhibit epidermal growth factor receptor (EGFR) tyrosine kinase. Interstitial lung disease (ILD) occurs in patients with non-small cell lung cancer receiving EGFR inhibitors. In the present study, we examined whether gefitinib- and erlotinib-induced lung injury related to ILD through endoplasmic reticulum (ER) stress, which is a causative intracellular mechanism in cytotoxicity caused by various chemicals in adenocarcinomic human alveolar basal epithelial cells. These two EGFR inhibitors increased Parkinson juvenile disease protein 2 and C/EBP homologous protein mRNA expressions, and activated the eukaryotic initiation factor (eIF) 2α/activating transcription factor 4 pathway without protein kinase R-like ER kinase activation in A549 cells. Gefitinib and erlotinib caused neither ER stress nor cell death; however, these agents inhibited cell growth via the reduction of cyclin-D1 expression. Tauroursodeoxycholic acid, which is known to suppress eIF2α phosphorylation, cancelled the effects of EGFR inhibitors on cyclin-D1 expression and cell proliferation in a concentration-dependent manner. The results of an EGFR-silencing study using siRNA showed that gefitinib and erlotinib affected eIF2α phosphorylation and cyclin-D1 expression independent of EGFR inhibition. Therefore, the inhibition of cell growth by these EGFR inhibitors might equate to impairment of the alveolar epithelial cell repair system via eIF2α phosphorylation and reduced cyclin-D1 expression.

  12. Transforming growth factor-β increases interleukin-13 synthesis via GATA-3 transcription factor in T-lymphocytes from patients with systemic sclerosis.

    Science.gov (United States)

    Baraut, Julie; Farge, Dominique; Jean-Louis, Francette; Masse, Ingrid; Grigore, Elena Ivan; Arruda, Lucas C M; Lamartine, Jérôme; Verrecchia, Franck; Michel, Laurence

    2015-07-31

    Transforming growth factor (TGF)-β and interleukin (IL)-13 play a crucial role in the pathogenesis of systemic sclerosis (SSc), partly through activation of collagen production that leads to fibrosis. The aim of the present study was to determine whether TFG-β alters IL-13 production in T lymphocytes from patients with SSc from that seen in those of healthy donors. IL-13 mRNA and protein synthesis under TFG-β exposure was measured in circulating T lymphocytes from healthy donors and patients with SSc and also in the Jurkat Th2 T-cell line, using quantitative real-time PCR and fluorescence-activated cell sorting analysis, respectively. The involvement of Smad and GATA-3 transcription factors was assessed by using specific inhibitors and small interfering RNA, and the binding capacity of GATA-3 to the IL-13 gene promoter was evaluated by chromatin immunoprecipitation assay. TGF-β induced a significant decrease in IL-13 mRNA and protein levels in lymphocytes from healthy donors (mean [±SD] inhibition of 30% ± 10% and 20% ± 7%, respectively; p T-cell subtypes from patients with SSc, with respective increases of 2.4 ± 0.3-fold, 1.6 ± 0.05-fold and 2.7 ± 0.02-fold. The involvement of the Smad signaling pathway and upregulation of GATA-3 binding capacity on the IL-13 promoter in lymphocytes from patients with SSc contributed to the effect of TGF-β on IL-13 production. These results demonstrate that TGF-β upregulates IL-13 synthesis through GATA-3 expression in the T lymphocytes of patients with SSc, confirming that the GATA-3 transcription factor can be regarded as a novel therapeutic target in patients with SSc.

  13. Transforming growth factor-beta, but not ciliary neurotrophic factor, inhibits DNA synthesis of adrenal medullary cells in vitro

    DEFF Research Database (Denmark)

    Wolf, N; Krohn, K; Bieger, S

    1999-01-01

    of fibroblast growth factor-2 and insulin-like growth factor-II, transforming growth factor-beta1 (0.08 nM) reduced 5-bromo-2'-deoxyuridine labeling by about 50%, without interfering with chromaffin cell survival or death. Doses lower and higher than 0.08 nM were less effective. Similar effects were seen...... immunocytochemistry as a marker for young postnatal rat chromaffin cells, we show that treatment with fibroblast growth factor-2 (1 nM) and insulin-like growth factor-II (10 nM) increased the fraction of 5-bromo-2'-deoxyuridine-labeled nuclei from 1% to about 40% of the cells in the absence of serum. In the presence...... by the neuroendocrine chromaffin cells, which also express the transforming growth factor-beta receptor type II. In contrast to the developmentally related sympathetic neurons, chromaffin cells continue to proliferate throughout postnatal life. Using 5-bromo-2'-deoxyuridine pulse labeling and tyrosine hydroxylase...

  14. Paracrine Fibroblast Growth Factor Initiates Oncogenic Synergy with Epithelial FGFR/Src Transformation in Prostate Tumor Progression.

    Science.gov (United States)

    Li, Qianjin; Ingram, Lishann; Kim, Sungjin; Beharry, Zanna; Cooper, Jonathan A; Cai, Houjian

    2018-03-01

    Cross talk of stromal-epithelial cells plays an essential role in both normal development and tumor initiation and progression. Fibroblast growth factor (FGF)-FGF receptor (FGFR)-Src kinase axis is one of the major signal transduction pathways to mediate this cross talk. Numerous genomic studies have demonstrated that expression levels of FGFR/Src are deregulated in a variety of cancers including prostate cancer; however, the role that paracrine FGF (from stromal cells) plays in dysregulated expression of epithelial FGFRs/Src and tumor progression in vivo is not well evaluated. In this study, we demonstrate that ectopic expression of wild-type FGFR1/2 or Src kinase in epithelial cells was not sufficient to initiate prostate tumorigenesis under a normal stromal microenvironment in vivo. However, paracrine FGF10 synergized with ectopic expression of epithelial FGFR1 or FGFR2 to induce epithelial-mesenchymal transition. Additionally, paracrine FGF10 sensitized FGFR2-transformed epithelial cells to initiate prostate tumorigenesis. Next, paracrine FGF10 also synergized with overexpression of epithelial Src kinase to high-grade tumors. But loss of the myristoylation site in Src kinase inhibited paracrine FGF10-induced prostate tumorigenesis. Loss of myristoylation alters Src levels in the cell membrane and inhibited FGF-mediated signaling including inhibition of the phosphotyrosine pattern and FAK phosphorylation. Our study demonstrates the potential tumor progression by simultaneous deregulation of proteins in the FGF/FGFRs/Src signal axis and provides a therapeutic strategy of targeting myristoylation of Src kinase to interfere with the tumorigenic process. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  15. The same allele of translation initiation factor 4E mediates resistance against two Potyvirus spp. in Pisum sativum

    DEFF Research Database (Denmark)

    Bruun-Rasmussen, M.; Møller, I.S.; Tulinius, G.

    2007-01-01

    was overcome, and virus from these plants had a codon change causing an Arg to His change at position 116 of the predicted viral genome-linked protein (VPg). Accordingly, plants carrying the wlv resistance gene were infected upon inoculation with BYMV-W derived from cDNA with a His codon at position 116......Pathogenicity of two sequenced isolates of Bean yellow mosaic virus (BYMV) was established on genotypes of Pisum sativum L. reported to carry resistance genes to BYMV and other potyviruses. Resistance to the white lupin strain of BYMV (BYMV-W) is inherited as a recessive gene named wlv that maps...... to linkage group VI together with other Potyvirus resistances. One of these, sbm1, confers resistance to strains of Pea seedborne mosaic virus and previously has been identified as a mutant allele of the eukaryotic translation initiation factor 4E gene (eIF4E). Sequence comparison of eIF4E from BYMV...

  16. Directing factors affecting the synthesis of a MFI-type zeolite

    International Nuclear Information System (INIS)

    Vinaches, P.; Pergher, S.B.C.; Lopes, C.W.; Gomez-Hortiguela, L.; Finger, P.H.; Silva, B.A. da; Dallago, R.M.; Mignoni, M.L.

    2016-01-01

    Full text: Zeolites are crystalline tectosilicates constituted by (TO4) tetrahedra connected through the oxygens of their vertices. The importance of these materials is that their properties differ, due to their variable compositions and structures, leading to the possibility of applying them into different industries, for example, as catalyst in petroleum industry or sensors in quality control. One of the big questions in this area is about the understanding of the chemistry that directs to one or another type of zeolite. Another important question is the search of new zeolitic structures for new applications. One approach to answer both is the study of the structure-directing agents, which are inorganic or organic molecules used in the synthesis of zeolites. New and already-used molecules have been studied within different synthesis conditions and different techniques, as characterization or computational studies. And several attempts of rationalization were and, still, will be performed. In this research, an imidazolium-based compound was studied in hydrothermal zeolite synthesis as organic structure-directing agent (OSDA). The products were obtained with Si/Al or Si/(Al+Zn) compositions, proved by ICP data. X-ray diffractograms showed two different zeolitic types: MFI and TON. It was observed that when Zn was present in the synthesis gel, pure MFI phases were able to appear. But in his absence, the products were all mixtures of MFI and TON zeolites. It was also possible to distinguish both phases by SEM micrographs, as MFI had brick-like shape and TON appeared as needles. The obtained zeolites were stable until 900°C minimum, as tested by a TG/DTG/DSC experiment. To prove that the chosen OSDA directed these structures, a CHN analysis was performed, resulting in integrity of the molecules inside the zeolitic pores and cavities. Finally, a rationale about the location and conformation of the OSDA was needed to understand these experimental results. So, it was

  17. Directing factors affecting the synthesis of a MFI-type zeolite

    Energy Technology Data Exchange (ETDEWEB)

    Vinaches, P.; Pergher, S.B.C. [Universidade Federal de Rio Grande do Norte (UFRN), RN (Brazil); Lopes, C.W. [Institute of Chemical Technology, Mumbai (India); Gomez-Hortiguela, L. [Instituto de Catalisis y Petroleoquimica, Madrid (Spain); Finger, P.H.; Silva, B.A. da; Dallago, R.M.; Mignoni, M.L. [Universidade Regional Integrada do Alto Uruguai e das Missoes (URI), Erechim, RS (Brazil)

    2016-07-01

    Full text: Zeolites are crystalline tectosilicates constituted by (TO4) tetrahedra connected through the oxygens of their vertices. The importance of these materials is that their properties differ, due to their variable compositions and structures, leading to the possibility of applying them into different industries, for example, as catalyst in petroleum industry or sensors in quality control. One of the big questions in this area is about the understanding of the chemistry that directs to one or another type of zeolite. Another important question is the search of new zeolitic structures for new applications. One approach to answer both is the study of the structure-directing agents, which are inorganic or organic molecules used in the synthesis of zeolites. New and already-used molecules have been studied within different synthesis conditions and different techniques, as characterization or computational studies. And several attempts of rationalization were and, still, will be performed. In this research, an imidazolium-based compound was studied in hydrothermal zeolite synthesis as organic structure-directing agent (OSDA). The products were obtained with Si/Al or Si/(Al+Zn) compositions, proved by ICP data. X-ray diffractograms showed two different zeolitic types: MFI and TON. It was observed that when Zn was present in the synthesis gel, pure MFI phases were able to appear. But in his absence, the products were all mixtures of MFI and TON zeolites. It was also possible to distinguish both phases by SEM micrographs, as MFI had brick-like shape and TON appeared as needles. The obtained zeolites were stable until 900°C minimum, as tested by a TG/DTG/DSC experiment. To prove that the chosen OSDA directed these structures, a CHN analysis was performed, resulting in integrity of the molecules inside the zeolitic pores and cavities. Finally, a rationale about the location and conformation of the OSDA was needed to understand these experimental results. So, it was

  18. Eukaryotic initiation factor 5A and Ca2+/calmodulin-dependent protein kinase 1D modulate trophoblast cell function.

    Science.gov (United States)

    Qin, Xiaoli; Liang, Yan; Guo, Yuna; Liu, Xiaorui; Zeng, Weihong; Wu, Fan; Lin, Yi; Zhang, Yan

    2018-03-13

    Trophoblast cells regulate embryo implantation and placental development. Eukaryotic initiation factor 5A (eIF5A) is an initiator of translation involved in cellular processes, such as migration, proliferation, and apoptosis. However, the function of eIF5A in trophoblast cells is unknown. We inhibited eIF5A and Ca 2+ /calmodulin-dependent protein kinase 1D (CAMK1D) expression in HTR8 cells using RNA interference. The effects of eIF5A and CAMK1D on HTR8 cells were investigated using real-time polymerase chain reaction, Western blotting, flow cytometry, cell transfection assays, cell migration assays, and terminal deoxynucleotidyl transferase dUTP nick-end labeling. eIF5A inhibition decreased CAMK1D expression, proliferation, migration, and invasion, but upregulated apoptosis, in HTR8 cells. Cross-talk between eIF5A and CAMK1D enhances proliferation, migration, and invasion, but inhibits apoptosis, in trophoblasts. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Eukaryotic Translation Initiation Factor eIFiso4G Is Required to Regulate Violaxanthin De-epoxidase Expression in Arabidopsis*

    Science.gov (United States)

    Chen, Zhong; Jolley, Blair; Caldwell, Christian; Gallie, Daniel R.

    2014-01-01

    The eukaryotic translation initiation factor (eIF) 4G is a scaffold protein that organizes the assembly of those initiation factors needed to recruit the 40 S ribosomal subunit to an mRNA. Plants, like many eukaryotes, express two eIF4G isoforms. eIFiso4G, one of the isoforms specific to plants, is unique among eukaryotic eIF4G proteins in that it is highly divergent and unusually small in size, raising the possibility of functional specialization. In this study, the role of eIFiso4G in plant growth was investigated using null mutants for the eIF4G isoforms in Arabidopsis. eIFiso4G loss of function mutants exhibited smaller cell, leaf, plant size, and biomass accumulation that correlated with its reduced photosynthetic activity, phenotypes not observed with the eIF4G loss of function mutant. Although no change in photorespiration or dark respiration was observed in the eIFiso4G loss of function mutant, a reduction in chlorophyll levels and an increase in the level of nonphotochemical quenching were observed. An increase in xanthophyll cycle activity and the generation of reactive oxygen species contributed to the qE and qI components of nonphotochemical quenching, respectively. An increase in the transcript and protein levels of violaxanthin de-epoxidase in the eIFiso4G loss of function mutant and an increase in its xanthophyll de-epoxidation state correlated with the higher qE associated with loss of eIFiso4G expression. These observations indicate that eIFiso4G expression is required to regulate violaxanthin de-epoxidase expression and to support photosynthetic activity. PMID:24706761

  20. Eukaryotic translation initiation factor eIFiso4G is required to regulate violaxanthin De-epoxidase expression in Arabidopsis.

    Science.gov (United States)

    Chen, Zhong; Jolley, Blair; Caldwell, Christian; Gallie, Daniel R

    2014-05-16

    The eukaryotic translation initiation factor (eIF) 4G is a scaffold protein that organizes the assembly of those initiation factors needed to recruit the 40 S ribosomal subunit to an mRNA. Plants, like many eukaryotes, express two eIF4G isoforms. eIFiso4G, one of the isoforms specific to plants, is unique among eukaryotic eIF4G proteins in that it is highly divergent and unusually small in size, raising the possibility of functional specialization. In this study, the role of eIFiso4G in plant growth was investigated using null mutants for the eIF4G isoforms in Arabidopsis. eIFiso4G loss of function mutants exhibited smaller cell, leaf, plant size, and biomass accumulation that correlated with its reduced photosynthetic activity, phenotypes not observed with the eIF4G loss of function mutant. Although no change in photorespiration or dark respiration was observed in the eIFiso4G loss of function mutant, a reduction in chlorophyll levels and an increase in the level of nonphotochemical quenching were observed. An increase in xanthophyll cycle activity and the generation of reactive oxygen species contributed to the qE and qI components of nonphotochemical quenching, respectively. An increase in the transcript and protein levels of violaxanthin de-epoxidase in the eIFiso4G loss of function mutant and an increase in its xanthophyll de-epoxidation state correlated with the higher qE associated with loss of eIFiso4G expression. These observations indicate that eIFiso4G expression is required to regulate violaxanthin de-epoxidase expression and to support photosynthetic activity. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Eukaryotic initiation factor 4G suppresses nonsense-mediated mRNA decay by two genetically separable mechanisms.

    Science.gov (United States)

    Joncourt, Raphael; Eberle, Andrea B; Rufener, Simone C; Mühlemann, Oliver

    2014-01-01

    Nonsense-mediated mRNA decay (NMD), which is best known for degrading mRNAs with premature termination codons (PTCs), is thought to be triggered by aberrant translation termination at stop codons located in an environment of the mRNP that is devoid of signals necessary for proper termination. In mammals, the cytoplasmic poly(A)-binding protein 1 (PABPC1) has been reported to promote correct termination and therewith antagonize NMD by interacting with the eukaryotic release factors 1 (eRF1) and 3 (eRF3). Using tethering assays in which proteins of interest are recruited as MS2 fusions to a NMD reporter transcript, we show that the three N-terminal RNA recognition motifs (RRMs) of PABPC1 are sufficient to antagonize NMD, while the eRF3-interacting C-terminal domain is dispensable. The RRM1-3 portion of PABPC1 interacts with eukaryotic initiation factor 4G (eIF4G) and tethering of eIF4G to the NMD reporter also suppresses NMD. We identified the interactions of the eIF4G N-terminus with PABPC1 and the eIF4G core domain with eIF3 as two genetically separable features that independently enable tethered eIF4G to inhibit NMD. Collectively, our results reveal a function of PABPC1, eIF4G and eIF3 in translation termination and NMD suppression, and they provide additional evidence for a tight coupling between translation termination and initiation.

  2. Factors Predictive of Tumor Recurrence and Survival After Initial Complete Response of Esophageal Squamous Cell Carcinoma to Definitive Chemoradiotherapy

    International Nuclear Information System (INIS)

    Ishihara, Ryu; Yamamoto, Sachiko; Iishi, Hiroyasu; Takeuchi, Yoji; Sugimoto, Naotoshi; Higashino, Koji; Uedo, Noriya; Tatsuta, Masaharu; Yano, Masahiko; Imai, Atsushi; Nishiyama, Kinji

    2010-01-01

    Purpose: To assess factors predictive of recurrent disease and survival after achieving initial complete response (CR) to chemoradiotherapy (CRT) for esophageal cancer. Methods and Materials: Patients who had clinical Stage I-IVA esophageal cancer and received definitive CRT between 2001 and 2007 were retrospectively analyzed. Results: Of 269 patients with esophageal cancer, 110 who achieved CR after definitive CRT were included in the analyses. Chemoradiotherapy mainly consisted of 2 cycles of cisplatin and fluorouracil with concurrent radiotherapy of 60 Gy in 30 fractions. We identified 28 recurrences and 28 deaths during follow-up. The cumulative 1- and 3-year recurrence rates were 18% and 32%, respectively. By univariate and multivariate analyses, tumor category (hazard ratio [HR] 6.6; 95% confidence interval [CI] 1.4-30.2; p = 0.015) was an independent risk factor for local recurrence, whereas age (HR 3.9; 95% CI 1.1-14.0; p = 0.034) and primary tumor location (HR 4.5; 95% CI 1.6-12.4; p = 0.004) were independent risk factors for regional lymph node or distant recurrences. The cumulative overall 1- and 3-year survival rates were 91% and 66%, respectively. As expected, recurrence was associated with poor survival (p = 0.019). By univariate and multivariate analyses, primary tumor location (HR 3.8; 95% CI 1.2-12.0; p = 0.024) and interval to recurrence (HR 4.3; 95% CI 1.3-14.4; p = 0.018) were independent factors predictive of survival after recurrence. Conclusion: Risk of recurrence after definitive CRT for esophageal cancer was associated with tumor category, age, and primary tumor location; this information may help in improved prognostication for these patients.

  3. Down-Regulation by Resveratrol of Basic Fibroblast Growth Factor-Stimulated Osteoprotegerin Synthesis through Suppression of Akt in Osteoblasts

    Science.gov (United States)

    Kuroyanagi, Gen; Otsuka, Takanobu; Yamamoto, Naohiro; Matsushima-Nishiwaki, Rie; Nakakami, Akira; Mizutani, Jun; Kozawa, Osamu; Tokuda, Haruhiko

    2014-01-01

    It is firmly established that resveratrol, a natural food compound abundantly found in grape skins and red wine, has beneficial properties for human health. In the present study, we investigated the effect of basic fibroblast growth factor (FGF-2) on osteoprotegerin (OPG) synthesis in osteoblast-like MC3T3-E1 cells and whether resveratrol affects the OPG synthesis. FGF-2 stimulated both the OPG release and the expression of OPG mRNA. Resveratrol significantly suppressed the FGF-2-stimulated OPG release and the mRNA levels of OPG. SRT1720, an activator of SIRT1, reduced the FGF-2-induced OPG release and the OPG mRNA expression. PD98059, an inhibitor of upstream kinase activating p44/p42 mitogen-activated protein (MAP) kinase, had little effect on the FGF-2-stimulated OPG release. On the other hand, SB203580, an inhibitor of p38 MAP kinase, SP600125, an inhibitor of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and Akt inhibitor suppressed the OPG release induced by FGF-2. Resveratrol failed to affect the FGF-2-induced phosphorylation of p44/p42 MAP kinase, p38 MAP kinase or SAPK/JNK. The phosphorylation of Akt induced by FGF-2 was significantly suppressed by resveratrol or SRT1720. These findings strongly suggest that resveratrol down-regulates FGF-2-stimulated OPG synthesis through the suppression of the Akt pathway in osteoblasts and that the inhibitory effect of resveratrol is mediated at least in part by SIRT1 activation. PMID:25290095

  4. Synaptic Plasticity and Translation Initiation

    Science.gov (United States)

    Klann, Eric; Antion, Marcia D.; Banko, Jessica L.; Hou, Lingfei

    2004-01-01

    It is widely accepted that protein synthesis, including local protein synthesis at synapses, is required for several forms of synaptic plasticity. Local protein synthesis enables synapses to control synaptic strength independent of the cell body via rapid protein production from pre-existing mRNA. Therefore, regulation of translation initiation is…

  5. A comparison of the effect of epidermal growth factor, platelet-derived growth factor, and fibroblast growth factor on rat periodontal ligament fibroblast-like cells' DNA synthesis and morphology

    DEFF Research Database (Denmark)

    Blom, S; Holmstrup, P; Dabelsteen, Erik

    1994-01-01

    of observations were assessed by the Student t-test. The morphogenic effects of growth factors were described with respect to growth pattern, cell orientation, and cell and nucleus form after a random photographic recording. The fibroblast-like cell type and the non-transformed phenotype of the cell line have...... nuclei. Incorporation of [3H]-thymidine was increased in a dose-dependent manner by all growth factors. Maximal effect on the DNA synthesis was: rEGF, 131%; nPDGF, 274%; and nFGF, 182%.(ABSTRACT TRUNCATED AT 250 WORDS)...

  6. Incidence and risk factors for lower limb lymphedema after gynecologic cancer surgery with initiation of periodic complex decongestive physiotherapy.

    Science.gov (United States)

    Deura, Imari; Shimada, Muneaki; Hirashita, Keiko; Sugimura, Maki; Sato, Seiya; Sato, Shinya; Oishi, Tetsuro; Itamochi, Hiroaki; Harada, Tasuku; Kigawa, Junzo

    2015-06-01

    Lower limb lymphedema (LLL) is one of the most frequent postoperative complications of retroperitoneal lymphadenectomy for gynecologic cancer. LLL often impairs quality of life, activities of daily living, sleep, and sex in patients with gynecologic cancer. We conducted this study to evaluate the incidence and risk factors for LLL after gynecologic cancer surgery in patients who received assessment and periodic complex decongestive physiotherapy (CDP). We retrospectively reviewed 126 cases of gynecologic cancer that underwent surgery involving retroperitoneal lymphadenectomy at Tottori University Hospital between 2009 and 2012. All patients received physical examinations to detect LLL and underwent CDP by nurse specialists within several months after surgery. The International Society of Lymphology staging of lymphedema severity was used as the diagnostic criteria. Of 126 patients, 57 (45.2%) had LLL, comprising 45 and 12 patients with stage 1 and stage 2 LLL, respectively. No patient had stage 3 LLL. LLL was present in 37 (29.4%) patients at the initial physical examination. Multivariate analysis revealed that adjuvant concurrent chemoradiotherapy and age ≥ 55 years were independent risk factors for ≥ stage 2 LLL. To minimize the incidence of ≥ stage 2 LLL, gynecologic oncologists should be vigilant for this condition in patients who are ≥ 55 years and in those who undergo adjuvant chemoradiotherapy. Patients should be advised to have a physical assessment for LLL and to receive education about CDP immediately after surgery involving retroperitoneal lymphadenectomy for gynecologic cancer.

  7. Factors associated with acceptance of provider-initiated HIV testing and counseling among pregnant women in Ethiopia

    Directory of Open Access Journals (Sweden)

    Gebremedhin KB

    2018-01-01

    Full Text Available Ketema Bizuwork Gebremedhin,1 Bingjie Tian,2 Chulei Tang,3 Xiaoxia Zhang,3 Engida Yisma,1,4 Honghong Wang3 1Department of Nursing and Midwifery, School of Allied Health Sciences, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; 2Department of General Surgery, Affiliated Huashan Hospital of Fudan University, Shanghai, China; 3Department of Fundamental Nursing, Xiangya School of Nursing, Central South University, Changsha, China; 4School of Medicine, Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia Introduction: The global human immunodeficiency virus (HIV epidemic disproportionately affects sub-Saharan African countries, including Ethiopia. Provider-initiated HIV testing and counseling (PITC is a tool to identify HIV-positive pregnant women and an effective treatment and prevention strategy. However, its success depends upon the willingness of pregnant women to accept HIV testing.Objectives: To describe the level of acceptance of PITC and associated factors among pregnant women attending 8 antenatal care clinics in Adama, Ethiopia.Methods: Trained nursing students and employees from an HIV clinic conducted face-to-face structured interviews in private offices at the clinics from August to September, 2016.Results: Among the 441 respondents, 309 (70.1% accepted PITC. Women with more antenatal care visits (odds ratio [OR] =2.59, 95% CI: 1.01–6.63, reported better quality of the PITC service (OR =1.91, 95% CI: 1.19–3.08, and higher level of knowledge on mother-to-child transmission (OR =1.82, 95% CI: 1.03–3.20, were more likely to accept PITC, while women who were older in age (OR =0.37, 95% CI: 0.19–0.74 and perceived negative attitudes from their partners toward HIV-positive results (OR =0.31, 95% CI: 0.10–0.94 were less likely to accept the PITC service.Conclusion: About one-third of pregnant women are not willing to accept PITC. When designing intervention program to improve the

  8. Eukaryotic Translation Initiation Factor 4E Is a Feed-Forward Translational Coactivator of Transforming Growth Factor β Early Protransforming Events in Breast Epithelial Cells.

    Science.gov (United States)

    Decarlo, Lindsey; Mestel, Celine; Barcellos-Hoff, Mary-Helen; Schneider, Robert J

    2015-08-01

    Eukaryotic translation initiation factor 4E (eIF4E) is overexpressed early in breast cancers in association with disease progression and reduced survival. Much remains to be understood regarding the role of eIF4E in human cancer. We determined, using immortalized human breast epithelial cells, that elevated expression of eIF4E translationally activates the transforming growth factor β (TGF-β) pathway, promoting cell invasion, a loss of cell polarity, increased cell survival, and other hallmarks of early neoplasia. Overexpression of eIF4E is shown to facilitate the selective translation of integrin β1 mRNA, which drives the translationally controlled assembly of a TGF-β receptor signaling complex containing α3β1 integrins, β-catenin, TGF-β receptor I, E-cadherin, and phosphorylated Smad2/3. This receptor complex acutely sensitizes nonmalignant breast epithelial cells to activation by typically substimulatory levels of activated TGF-β. TGF-β can promote cellular differentiation or invasion and transformation. As a translational coactivator of TGF-β, eIF4E confers selective mRNA translation, reprogramming nonmalignant cells to an invasive phenotype by reducing the set point for stimulation by activated TGF-β. Overexpression of eIF4E may be a proinvasive facilitator of TGF-β activity. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  9. Expression of nerve growth factor and its receptors in the uterus of rabbits: functional involvement in prostaglandin synthesis.

    Science.gov (United States)

    Maranesi, M; Parillo, F; Leonardi, L; Rebollar, P G; Alonso, B; Petrucci, L; Gobbetti, A; Boiti, C; Arruda-Alencar, J; Moura, A; Zerani, M

    2016-07-01

    The aim of the present study was to evaluate: (1) the presence of nerve growth factor (NGF), neurotrophic tyrosine kinase receptor 1 (NTRK1), and nerve growth factor receptor (NGFR) in the rabbit uterus; and (2) the in vitro effects of NGF on PGF2α and PGE2 synthesis and on the PGE2-9-ketoreductase (PGE2-9-K) activity by the rabbit uterus. Nerve growth factor, NTRK1, and NGFR were immunolocalized in the luminal and glandular epithelium and stroma cells of the endometrium. reverse transcriptase polymerase chain reaction indicated the presence of messenger RNA for NGF, NTRK1, and NGFR in the uterus. Nerve growth factor increased (P uterus. NGF/NTRK1 increases PGF2α and PGE2 productions by upregulating NOS and PGE2-9-K activities, whereas NGF/NGFR augments only PGF2α secretion, through an intracellular mechanism that is still unknown. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Modifiable worker risk factors contributing to workplace absence: a stakeholder-centred best-evidence synthesis of systematic reviews.

    Science.gov (United States)

    Wagner, Shannon; White, Marc; Schultz, Izabela; Murray, Eleanor; Bradley, Susan M; Hsu, Vernita; McGuire, Lisa; Schulz, Werner

    2014-01-01

    A challenge facing stakeholders is the identification and translation of relevant high quality research to inform policy and practice. This study engaged academic and community stakeholders in conducting a best evidence-synthesis to identify modifiable risk and protective worker factors across health conditions impacting work-related absence. To identify modifiable worker disability risk and protective factors across common health conditions impacting work-related absence. We searched Medline, Embase, CINHAL, The Cochrane Library, PsycINFO, BusinessSourceComplete, and ABI/Inform from 2000 to 2011. Quantitative, qualitative, or mixed methods systematic reviews of work-focused population were considered for inclusion. Two or more reviewers independently reviewed articles for inclusion and methodological screening. The search strategy, expert input and grey literature identified 2,467 unique records. One hundred and forty-two full text articles underwent comprehensive review. Twenty-four systematic reviews met eligibility criteria. Modifiable worker factors found to have consistent evidence across two or more health conditions included emotional distress, negative enduring psychology/personality factors, negative health and disability perception, decreased physical activity, lack of family support, poor general health, increased functional disability, increased pain, increased fatigue and lack of motivation to return to work. Systematic reviews are limited by availability of high quality studies, lack of consistency of methodological screening and reporting, and variability of outcome measures used.

  11. Effect of nerve growth factor on the synthesis of amino acids in PC12 cells

    International Nuclear Information System (INIS)

    Zielke, H.R.; Tildon, J.T.; Kauffman, F.C.; Baab, P.J.

    1989-01-01

    Radioactive short-chain fatty acids preferentially label glutamine relative to glutamate in brain due to compartmentation of glutamine and glutamate. To determine whether this phenomenon occurs in a single cell culture model, we examined the effect of fatty acid chain length on the synthesis as well as pool size of selected amino acids in rat pheochromocytoma PC12 cells, a cell culture model of the large glutamate compartment in neurons. Intracellular 14C-amino acids were quantitated by HPLC, and the incorporation of [U-14C]-glucose, [1-14C]-butyrate, [1-14C]-octanoate, and [1-14C]-palmitate into five amino acids was measured in native and NGF-treated PC12 cells. NGF pretreatment decreased the intracellular concentration of amino acids as did addition of fatty acids but these effects were not additive. Specific activities of amino acids in native cells labelled by 14C-octanoate were 1,300 DPM/nmol, 490 DPM/nmol, 200 DPM/nmol, and 110 DPM/nmol for glutamate, aspartate, glutamine, and serine, respectively. No radioactivity was detected in alanine. Similar specific activities were noted when 14C-butyrate was the precursor; however, there was at least 5-fold less if 14C-palmitate was the precursor. Pretreatment of cells with NGF decreased the specific activity of amino acids by 25-65%. Specific activities of amino acids synthesized from 14C-glucose decreased in the following order: glutamate, 1,640 DPM/nmol; aspartate, 1,210 DPM/nmol; alanine, 580 DPM/nmol; glutamine, 275 DPM/nmol; and serine, 80 DPM/nmol for native cells. NGF pretreatment decreased the specific activities of glutamate and glutamine, but not of the other 3 amino acids. The preferred precursor for glutamate synthesis in native PC12 cells was glucose followed by octanoate, butyrate and palmitate (16:6:3:1)

  12. Synthesis of trideuterated O-alkyl platelet activating factor and lyso derivatives

    International Nuclear Information System (INIS)

    Prakash, C.; Saleh, S.; Taber, D.F.; Blair, I.A.

    1989-01-01

    Racemic heavy isotope analogs of 1-O-alkyl-sn-glycero-3-phosphocholine (lysoPAF) and 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine (PAF) were prepared for use as internal standards to facilitate quantitative studies based on mass spectrometry. Starting from pentadecane-1,15-diol and rac-glycerol-1,2-acetonide, a convergent synthesis of 1-O-[16'-2H3]hexadecyl and 1-O-[18'-2H3]octadecyl rac-glycero-3-phosphocholine and their acetyl derivatives is described. Three deuterium atoms were introduced at the terminal position of the 1-O-alkyl group by displacement of the p-toluensulfonyl group from 1-O-alkyl-15'-p-toluensulfonate and 1-O-alkyl-17'-p-toluensulfonate with [2H3]-methylmagnesium iodide. The 1-O-alkyl-17'-p-toluensulfonate was obtained by reaction of the 1-O-alkyl-15'-p-toluensulfonate with allylmagnesium bromide, followed by reductive ozonolysis and treatment with p-toluene-sulfonyl chloride. The hydroxyl group at C-2 was protected by a benzyl group and removed at a late stage in the synthesis. This provided the corresponding lyso-derivatives or allowed preparation of racemic PAF by subsequent acetylation of the free hydroxy group. The phosphocholine moiety was introduced at glycerol C-3 by reaction with bromoethyldichlorophosphate and trimethylamine. The synthetic compounds were analyzed by FAB/MS and GC/NICIMS. They were shown to contain less than 0.6% protium impurity

  13. Rheb Inhibits Protein Synthesis by Activating the PERK-eIF2α Signaling Cascade

    Directory of Open Access Journals (Sweden)

    Richa Tyagi

    2015-02-01

    Full Text Available Rheb, a ubiquitous small GTPase, is well known to bind and activate mTOR, which augments protein synthesis. Inhibition of protein synthesis is also physiologically regulated. Thus, with cell stress, the unfolded protein response system leads to phosphorylation of the initiation factor eIF2α and arrest of protein synthesis. We now demonstrate a major role for Rheb in inhibiting protein synthesis by enhancing the phosphorylation of eIF2α by protein kinase-like ER kinase (PERK. Interplay between the stimulatory and inhibitory roles of Rheb may enable cells to modulate protein synthesis in response to varying environmental stresses.

  14. [Breastfeeding (part one): Frequency, benefits and drawbacks, optimal duration and factors influencing its initiation and prolongation. Clinical guidelines for practice].

    Science.gov (United States)

    Chantry, A A; Monier, I; Marcellin, L

    2015-12-01

    The objectives were to on assess the frequency and the duration of breastfeeding in France. On the other hand, the objectives were to identify its benefits and drawbacks, and to study the factors influencing its initiation and its extension. Bibliographic research in Medline, Google Scholar and in the Cochrane Library. Breastfeeding concerns in France about 70% of children at birth (EL2). Its median duration is about 15 weeks and 3 weeks ½ for exclusive breastfeeding. At three months, only one third of children breastfed at birth are still being breastfed (EL2). Whether this is due to the composition of breast milk or the behavior of mothers with their children or their socio-cultural level, or even by all these components at once, breastfeeding is associated with better cognitive development children (EL2). This effect is even more reinforced that mothers breastfeed exclusively and prolonged (EL2). As part of the prevention of many diseases (ear infections, gastrointestinal infections, atopic diseases, obesity and cardiovascular diseases…), exclusive and prolonged breastfeeding (grade B) between 4 to 6 months is recommended (professional consensus). Breastfeeding is not a means of preventing postpartum depression (professional consensus). To reduce the incidence of breast cancer, prolonged breastfeeding is recommended (grade B). In order to increase the rate of initiation of breastfeeding as well as its duration, it is recommended that health professionals work closely with mothers in their project (grade A), the breastfeeding promotion messages include message to husbands (grade B), and to promote breastfeeding on demand without fixed interval between feedings (grade B). However, there is not enough data to recommend the use of a specific position during breastfeeding, or the use of one or two breast or to early start breastfeeding or not (professional consensus). Exclusive and extended breastfeeding is recommended (grade B) between 4 to 6 months (professional

  15. Synthesis and Complete Structure Determination of a Sperm-Activating and -Attracting Factor Isolated from the Ascidian Ascidia sydneiensis.

    Science.gov (United States)

    Watanabe, Tomohiro; Shibata, Hajime; Ebine, Makoto; Tsuchikawa, Hiroshi; Matsumori, Nobuaki; Murata, Michio; Yoshida, Manabu; Morisawa, Masaaki; Lin, Shu; Yamauchi, Kosei; Sakai, Ken; Oishi, Tohru

    2018-03-28

    For the complete structure elucidation of an endogenous sperm-activating and -attracting factor isolated from eggs of the ascidian Ascidia sydneiensis ( Assydn-SAAF), its two possible diastereomers with respect to C-25 were synthesized. Starting from ergosterol, the characteristic steroid backbone was constructed by using an intramolecular pinacol coupling reaction and stereoselective reduction of a hydroxy ketone as key steps, and the side chain was introduced by Julia-Kocienski olefination. Comparison of the NMR data of the two diastereomers with those of the natural product led to the elucidation of the absolute configuration as 25 S; thus the complete structure was determined and the first synthesis of Assydn-SAAF was achieved.

  16. Baculovirus DNA Replication-Specific Expression Factors Trigger Apoptosis and Shutoff of Host Protein Synthesis during Infection▿

    Science.gov (United States)

    Schultz, Kimberly L. W.; Friesen, Paul D.

    2009-01-01

    Apoptosis is an important antivirus defense. To define the poorly understood pathways by which invertebrates respond to viruses by inducing apoptosis, we have identified replication events that trigger apoptosis in baculovirus-infected cells. We used RNA silencing to ablate factors required for multiplication of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV). Transfection with double-stranded RNA (dsRNA) complementary to the AcMNPV late expression factors (lefs) that are designated as replicative lefs (lef-1, lef-2, lef-3, lef-11, p143, dnapol, and ie-1/ie-0) blocked virus DNA synthesis and late gene expression in permissive Spodoptera frugiperda cells. dsRNAs specific to designated nonreplicative lefs (lef-8, lef-9, p47, and pp31) blocked late gene expression without affecting virus DNA replication. Thus, both classes of lefs functioned during infection as defined. Silencing the replicative lefs prevented AcMNPV-induced apoptosis of Spodoptera cells, whereas silencing the nonreplicative lefs did not. Thus, the activity of replicative lefs or virus DNA replication is sufficient to trigger apoptosis. Confirming this conclusion, AcMNPV-induced apoptosis was suppressed by silencing the replicative lefs in cells from a divergent species, Drosophila melanogaster. Silencing replicative but not nonreplicative lefs also abrogated AcMNPV-induced shutdown of host protein synthesis, suggesting that virus DNA replication triggers inhibition of host biosynthetic processes and that apoptosis and translational arrest are linked. Our findings suggest that baculovirus DNA replication triggers a host cell response similar to the DNA damage response in vertebrates, which causes translational arrest and apoptosis. Pathways for detecting virus invasion and triggering apoptosis may therefore be conserved between insects and mammals. PMID:19706708

  17. Baculovirus DNA replication-specific expression factors trigger apoptosis and shutoff of host protein synthesis during infection.

    Science.gov (United States)

    Schultz, Kimberly L W; Friesen, Paul D

    2009-11-01

    Apoptosis is an important antivirus defense. To define the poorly understood pathways by which invertebrates respond to viruses by inducing apoptosis, we have identified replication events that trigger apoptosis in baculovirus-infected cells. We used RNA silencing to ablate factors required for multiplication of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV). Transfection with double-stranded RNA (dsRNA) complementary to the AcMNPV late expression factors (lefs) that are designated as replicative lefs (lef-1, lef-2, lef-3, lef-11, p143, dnapol, and ie-1/ie-0) blocked virus DNA synthesis and late gene expression in permissive Spodoptera frugiperda cells. dsRNAs specific to designated nonreplicative lefs (lef-8, lef-9, p47, and pp31) blocked late gene expression without affecting virus DNA replication. Thus, both classes of lefs functioned during infection as defined. Silencing the replicative lefs prevented AcMNPV-induced apoptosis of Spodoptera cells, whereas silencing the nonreplicative lefs did not. Thus, the activity of replicative lefs or virus DNA replication is sufficient to trigger apoptosis. Confirming this conclusion, AcMNPV-induced apoptosis was suppressed by silencing the replicative lefs in cells from a divergent species, Drosophila melanogaster. Silencing replicative but not nonreplicative lefs also abrogated AcMNPV-induced shutdown of host protein synthesis, suggesting that virus DNA replication triggers inhibition of host biosynthetic processes and that apoptosis and translational arrest are linked. Our findings suggest that baculovirus DNA replication triggers a host cell response similar to the DNA damage response in vertebrates, which causes translational arrest and apoptosis. Pathways for detecting virus invasion and triggering apoptosis may therefore be conserved between insects and mammals.

  18. Critical Factors in Reading Comprehension Instruction for Students with Learning Disabilities: A Research Synthesis

    Science.gov (United States)

    Kim, Woori; Linan-Thompson, Sylvia; Misquitta, Radhika

    2012-01-01

    This review examined the effectiveness of critical factors in instruction for improving the reading comprehension of middle school students with learning disabilities. Five critical factors were identified: (i) type of instructional methods, (ii) self-monitoring, (iii) components of reading incorporated, (iv) fidelity of instruction (scripted vs.…

  19. A Synthesis and Survey of Critical Success Factors for Computer Technology Projects

    Science.gov (United States)

    Baker, Ross A.

    2012-01-01

    The author investigated the existence of critical success factors for computer technology projects. Current research literature and a survey of experienced project managers indicate that there are 23 critical success factors (CSFs) that correlate with project success. The survey gathered an assessment of project success and the degree to which…

  20. Eukaryotic initiation factor eIF6 modulates the expression of Kermit 2/XGIPC in IGF- regulated eye development.

    Science.gov (United States)

    De Marco, N; Tussellino, M; Carotenuto, R; Ronca, R; Rizzolio, S; Biffo, S; Campanella, C

    2017-07-01

    The eukaryotic initiation translation factor eIF6 is a highly conserved, essential protein implicated in translation. eIF6 is regulated in vivo by extracellular signals, such as IGF signaling (for a review see Miluzio et al., 2009). In Xenopus, eif6 over-expression causes a delay in eye development (De Marco et al., 2011). In this study we showed that eif6 co-immunoprecipitates with the insulin-like growth factor receptor (igfr) and may function downstream of igf in eye formation. The relationship between eif6 and gipc2, a protein partner of a variety of molecules including membrane proteins, was investigated. gipc2 is required for maintaining igf-induced akt activation on eye development (Wu et al., 2006). Significantly eif6 and gipc2 have opposite effects in eye development. While eif6 is required for eye formation below threshold levels, gipc2 knockdown impairs eye development (De Marco et al., 2011; Wu et al., 2006). In this study, it was shown that in eif6 over-expressors, the delay in eye morphogenesis is reversed by gipc2 injection, while the injection of eif6 down-regulates gipc2 expression. Real-time-PCR indicates that eif6 regulates gipc2 expression in a dose-dependent manner. In contrast, gipc2 knockdown has no significant effect on eif6 mRNA levels. These results suggest that eif6 regulation of gipc2 enables correct morphogenesis of Xenopus eye and stimulate questions on the molecular network implicated in this process. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Risk factors for late-stage HIV disease presentation at initial HIV diagnosis in Durban, South Africa.

    Directory of Open Access Journals (Sweden)

    Paul K Drain

    Full Text Available After observing persistently low CD4 counts at initial HIV diagnosis in South Africa, we sought to determine risk factors for late-stage HIV disease presentation among adults.We surveyed adults prior to HIV testing at four outpatient clinics in Durban from August 2010 to November 2011. All HIV-infected adults were offered CD4 testing, and late-stage HIV disease was defined as a CD4 count <100 cells/mm(3. We used multivariate regression models to determine the effects of sex, emotional health, social support, distance from clinic, employment, perceived barriers to receiving healthcare, and foregoing healthcare to use money for food, clothing, or housing ("competing needs to healthcare" on presentation with late-stage HIV disease.Among 3,669 adults screened, 830 were enrolled, newly-diagnosed with HIV and obtained a CD4 result. Among those, 279 (33.6% presented with late-stage HIV disease. In multivariate analyses, participants who lived ≥5 kilometers from the test site [adjusted odds ratio (AOR 2.8, 95% CI 1.7-4.7], reported competing needs to healthcare (AOR 1.7, 95% CI 1.2-2.4, were male (AOR 1.7, 95% CI 1.2-2.3, worked outside the home (AOR 1.5, 95% CI 1.1-2.1, perceived health service delivery barriers (AOR 1.5, 95% CI 1.1-2.1, and/or had poor emotional health (AOR 1.4, 95% CI 1.0-1.9 had higher odds of late-stage HIV disease presentation.Independent risk factors for late-stage HIV disease presentation were from diverse domains, including geographic, economic, demographic, social, and psychosocial. These findings can inform various interventions, such as mobile testing or financial assistance, to reduce the risk of presentation with late-stage HIV disease.

  2. Thrombin generation and fibrin clot formation under hypothermic conditions: an in vitro evaluation of tissue factor initiated whole blood coagulation.

    Science.gov (United States)

    Whelihan, Matthew F; Kiankhooy, Armin; Brummel-Ziedins, Kathleen E

    2014-02-01

    Despite trauma-induced hypothermic coagulopathy being familiar in the clinical setting, empirical experimentation concerning this phenomenon is lacking. In this study, we investigated the effects of hypothermia on thrombin generation, clot formation, and global hemostatic functions in an in vitro environment using a whole blood model and thromboelastography, which can recapitulate hypothermia. Blood was collected from healthy individuals through venipuncture and treated with corn trypsin inhibitor, to block the contact pathway. Coagulation was initiated with 5pM tissue factor at temperatures 37°C, 32°C, and 27°C. Reactions were quenched over time, with soluble and insoluble components analyzed for thrombin generation, fibrinogen consumption, factor (f)XIII activation, and fibrin deposition. Global coagulation potential was evaluated through thromboelastography. Data showed that thrombin generation in samples at 37°C and 32°C had comparable rates, whereas 27°C had a much lower rate (39.2 ± 1.1 and 43 ± 2.4 nM/min vs 28.6 ± 4.4 nM/min, respectively). Fibrinogen consumption and fXIII activation were highest at 37°C, followed by 32°C and 27°C. Fibrin formation as seen through clot weights also followed this trend. Thromboelastography data showed that clot formation was fastest in samples at 37°C and lowest at 27°C. Maximum clot strength was similar for each temperature. Also, percent lysis of clots was highest at 37°C followed by 32°C and then 27°C. Induced hypothermic conditions directly affect the rate of thrombin generation and clot formation, whereas global clot stability remains intact. © 2013.

  3. Risk factors of vitamin D deficiency in children with epilepsy taking anticonvulsants at initial and during follow-up

    Directory of Open Access Journals (Sweden)

    Seung Ho Lee

    2015-12-01

    Full Text Available PurposeVitamin D status was evaluated in children with epilepsy taking anticonvulsants to determine the prevalence and risk factors of vitamin D deficiency.MethodsThis study was designed as both a cross-sectional and a retrospective cohort study. A sum of 198 children who were diagnosed with epilepsy at the Department of Pediatrics in Dankook University Hospital was included. Their serum vitamin D levels were reviewed based on clinical information, and analyzed using IBM SPSS ver. 20.0.ResultsOne hundred twenty-four children (62.6% had vitamin D deficiency. Two risk factors were associated: winter to spring season (odds ratio [OR], 3.71; 95% confidence interval [CI], 1.835-7.492 and age more than 12 years (OR, 3.22; 95% CI, 1.377-7.542. Out of the 57 patients who were not vitamin D deficient at the time of initial assay, 47 patients (82.5% became vitamin D deficient during followup. The change of serum 25-hydroxy vitamin D3 (25(OHD levels during follow up showed a weak negative correlation with the duration of medication (r=-0.283, P=0.033. Medication duration was longer and brain magnetic resonance imaging (MRI abnormality, abnormal underlying conditions, and nonambulatory status were more frequently present in twenty-five patients (44% who showed a decline of more than 15 ng/mL during follow-up (P<0.05.ConclusionVitamin D deficiency is common in children with epilepsy taking anticonvulsants, especially in adolescents more than 12 years of age. This study emphasizes the regular monitoring of vitamin D level, especially in the presence of longer duration of medication, brain MRI abnormality, abnormal underlying conditions, and nonambulatory status.

  4. Depletion of elongation initiation factor 4E binding proteins by CRISPR/Cas9 genome editing enhances antiviral response in porcine cells

    Science.gov (United States)

    Type I interferons (IFN) are key mediators of the innate antiviral response in mammalian cells. Elongation initiation factor 4E binding proteins (4E-BPs) are translational controllers of interferon regulatory factor 7 (IRF7), the master regulator of IFN transcription. The role of 4EBPs in the negat...

  5. A review on granules initiation and development inside UASB Reactor and the main factors affecting granules formation process

    Energy Technology Data Exchange (ETDEWEB)

    Habeeb, S.A.; Latiff, Ab Aziz Bin Abdul; Daud, Zawawi Bin; Ahmad, Zulkifli Bin [Civil and Environmental Engineering, University Tun Hussein Onn Malaysia (Malaysia)

    2011-07-01

    Decades of investigations and explorations in the field of anaerobic wastewater treatment have resulted in significant indications about the role importance of sludge granules in biodegradation anaerobic process. It is believed that the development of anaerobic granules is reflecting an important role on the performance of reactor. An overview on the concept of up-flow anaerobic sludge bed (UASB) reactor operation as well as the main parts that reactor consists of is briefly explained in this paper, whereas the major theories of anaerobic granules formation are listed by related researchers. The correlations and compositions of such sludge granule have been specifically explained. It is believed that the extracellular polymer (ECP) is totally responsible of bacterial cell correlations and the formation of bacterial communities in the form of granules. In addition, the dependable factors for the performance of anaerobic granules formation process e.g. temperature, organic loading rate, pH, and alkalinity, nutrients, and cations and heavy metals have been discussed in this paper. Strong evidences proved that the process of gas production in the form of biogas is related to the methanogens activities, which are practically found in the core of granules. The aim of this review is to explore and assess the mechanisms of granules initiation and development inside UASB reactor.

  6. Official ERS technical standards: Global Lung Function Initiative reference values for the carbon monoxide transfer factor for Caucasians.

    Science.gov (United States)

    Stanojevic, Sanja; Graham, Brian L; Cooper, Brendan G; Thompson, Bruce R; Carter, Kim W; Francis, Richard W; Hall, Graham L

    2017-09-01

    There are numerous reference equations available for the single-breath transfer factor of the lung for carbon monoxide ( T  LCO ); however, it is not always clear which reference set should be used in clinical practice. The aim of the study was to develop the Global Lung Function Initiative (GLI) all-age reference values for T  LCO Data from 19 centres in 14 countries were collected to define T  LCO reference values. Similar to the GLI spirometry project, reference values were derived using the LMS (lambda, mu, sigma) method and the GAMLSS (generalised additive models for location, scale and shape) programme in R.12 660 T  LCO measurements from asymptomatic, lifetime nonsmokers were submitted; 85% of the submitted data were from Caucasians. All data were uncorrected for haemoglobin concentration. Following adjustments for elevation above sea level, gas concentration and assumptions used for calculating the anatomic dead space volume, there was a high degree of overlap between the datasets. Reference values for Caucasians aged 5-85 years were derived for T  LCO , transfer coefficient of the lung for carbon monoxide and alveolar volume.This is the largest collection of normative T  LCO data, and the first global reference values available for T  LCO . Copyright ©ERS 2017.

  7. Initial boost release of transforming growth factor-β3 and chondrogenesis by freeze-dried bioactive polymer scaffolds.

    Science.gov (United States)

    Krüger, Jan Philipp; Machens, Isabel; Lahner, Matthias; Endres, Michaela; Kaps, Christian

    2014-12-01

    In cartilage regeneration, bio-activated implants are used in stem and progenitor cell-based microfracture cartilage repair procedures. Our aim was to analyze the chondrogenic potential of freeze-dried resorbable polymer-based polyglycolic acid (PGA) scaffolds bio-activated with transforming growth factor-β3 (TGFB3) on human subchondral mesenchymal progenitor cells known from microfracture. Progenitor cells derived from femur heads were cultured in the presence of freeze-dried TGFB3 in high-density pellet culture and in freeze-dried TGFB3-PGA scaffolds for chondrogenic differentiation. Progenitor cell cultures in PGA scaffolds as well as pellet cultures with and without continuous application of TGFB3 served as controls. Release studies showed that freeze-dried TGFB3-PGA scaffolds facilitate a rapid, initial boost-like release of 71.5% of TGFB3 in the first 10 h. Gene expression analysis and histology showed induction of typical chondrogenic markers like type II collagen and formation of cartilaginous tissue in TGFB3-PGA scaffolds seeded with subchondral progenitor cells and in pellet cultures stimulated with freeze-dried TGFB3. Chondrogenic differentiation in freeze-dried TGFB3-PGA scaffolds was comparable to cultures receiving TGFB3 continuously, while non-stimulated controls did not show chondrogenesis during prolonged culture for 14 days. These results suggest that bio-activated, freeze-dried TGFB3-PGA scaffolds have chondrogenic potential and are a promising tool for stem cell-mediated cartilage regeneration.

  8. A novel interaction between adrenergic receptors and the alpha-subunit of eukaryotic initiation factor 2B.

    Science.gov (United States)

    Klein, U; Ramirez, M T; Kobilka, B K; von Zastrow, M

    1997-08-01

    The alpha-subunit of eukaryotic initiation factor 2B (eIF-2B), a guanine nucleotide exchange protein that functions in regulation of translation, was observed to associate with the carboxyl-terminal cytoplasmic domains of the alpha2A- and alpha2B-adrenergic receptors in a yeast two-hybrid screen of a cDNA library prepared from 293 cells. This protein association was confirmed in vitro by affinity chromatography and was shown to be specific for a subset of G protein-coupled receptors, including the alpha2A-, alpha2B-, alpha2C-, and beta2-adrenergic receptors, but not the vasopressin (V2) receptor. Association of these proteins in vivo was confirmed by specific co-immunoprecipitation of eIF-2Balpha with full-length beta2-adrenergic receptors expressed in transfected 293 cells and by fluorescence microscopy showing co-localization of these proteins in intact cells. Remarkably, eIF-2Balpha co-localized with receptors exclusively in regions of the plasma membrane that are in contact with the extracellular medium, but failed to associate with membranes making cell-cell contacts. Overexpression of eIF-2Balpha in 293 cells caused a small (approximately 15%) but significant enhancement of beta2-adrenergic receptor-mediated activation of adenylyl cyclase, without affecting forskolin or V2 receptor-mediated activation. These observations suggest a new role for a previously identified guanine nucleotide exchange protein in membrane biology and cell signaling.

  9. Eukaryotic translation initiation factor 3, subunit C is overexpressed and promotes cell proliferation in human glioma U-87 MG cells.

    Science.gov (United States)

    Hao, Jinmin; Liang, Chaohui; Jiao, Baohua

    2015-06-01

    Disrupted protein translation is prevalent in tumours. Eukaryotic translation initiation factors (eIFs) were found to play an important role in various tumours. However, the involvement of eIFs in glioma remains to be elucidated. The present study explored the expression and the role of eIF 3, subunit C (eIF3c) in human glioma. The expression of eIF3c in glioma tissues was evaluated by immunohistochemistry. The impact of eIF3c inhibition on U-87 MG was explored in vitro and in vivo by lentivirus-mediated siRNA targeting eIF3c. The results revealed that overexpression of eIF3c was present in glioma tissues. Knockdown of eIF3c significantly impaired cell proliferation and colony formation, further induced cell cycle arrest and apoptosis in the U-87 MG cell line. Furthermore, tumoursphere formation in the U-87 MG glioma xenograft model was blocked by eIF3c knockdown. The involvement of eIF3c in the tumorigenesis of glioma was confirmed, suggesting eIF3c may be a promising therapy target in human glioma.

  10. Eukaryotic Translation Initiation Factor 3a (eIF3a) Promotes Cell Proliferation and Motility in Pancreatic Cancer.

    Science.gov (United States)

    Wang, Shu Qian; Liu, Yu; Yao, Min Ya; Jin, Jing

    2016-10-01

    Identifying a target molecule that is crucially involved in pancreatic tumor growth and metastasis is necessary in developing an effective treatment. The study aimed to investigate the role of the eukaryotic translation initiation factor 3a (eIF3a) in the cell proliferation and motility in pancreatic cancer. Our data showed that the expression of eIF3a was upregulated in pancreatic ductal adenocarcinoma as compared with its expression in normal pancreatic tissues. Knockdown of eIF3a by a specific shRNA caused significant decreases in cell proliferation and clonogenic abilities in pancreatic cancer SW1990 and Capan-1 cells. Consistently, the pancreatic cancer cell growth rates were also impaired in xenotransplanted mice. Moreover, wound-healing assay showed that depletion of eIF3a significantly slowed down the wound recovery processes in SW1990 and Capan-1 cells. Transwell migration and invasion assays further showed that cell migration and invasion abilities were significantly inhibited by knockdown of eIF3a in SW1990 and Capan-1 cells. Statistical analysis of eIF3a expression in 140 cases of pancreatic ductal adenocarcinoma samples revealed that eIF3a expression was significantly associated with tumor metastasis and TNM staging. These analyses suggest that eIF3a contributes to cell proliferation and motility in pancreatic ductal adenocarcinoma.

  11. Molecular cloning of the human gene for von Willebrand factor and identification of the transcription initiation site

    International Nuclear Information System (INIS)

    Collins, C.J.; Underdahl, J.P.; Levene, R.B.; Ravera, C.P.; Morin, M.J.; Dombalagian, M.J.; Ricca, G.; Livingston, D.M.; Lynch, D.C.

    1987-01-01

    A series of overlapping cosmid genomic clones have been isolated that contain the entire coding unit of the human gene for van Willebrand factor (vWf), a major component of the hemostatic system. The cloned segments span ≅ 175 kilobases of human DNA sequence, and hybridization analysis suggest that the vWf coding unit is ≅150 kilobases in length. Within one of these clones, the vWF transcription initiation site has been mapped and a portion of the vWf promoter region has been sequenced, revealing a typical TATA box, a downstream CCAAT box, and a perfect downstream repeat of the 8 base pairs containing the transcription start site. Sequencing of a segment of another genomic clone has revealed the vWF translation termination codon. Where tested, comparative restriction analysis of cloned and chromosomal DNA segments strongly suggests that no major alterations occurred during cloning and that there is only one complete copy of the vWf gene in the human haploid genome. Similar analyses of DNA from vWf-producing endothelial cells and nonexpressing leukocytes suggest that vWf gene expression is not accompanied by gross genomic rearrangements. In addition, there is significant homology of C-terminal coding sequences among the vWf genes of several vertebrate species

  12. Human DDX3 functions in translation and interacts with the translation initiation factor eIF3.

    Science.gov (United States)

    Lee, Chung-Sheng; Dias, Anusha P; Jedrychowski, Mark; Patel, Arvind H; Hsu, Jeanne L; Reed, Robin

    2008-08-01

    The conserved RNA helicase DDX3 is of major medical importance due to its involvement in numerous cancers, human hepatitis C virus (HCV) and HIV. Although DDX3 has been reported to have a wide variety of cellular functions, its precise role remains obscure. Here, we raised a new antibody to DDX3 and used it to show that DDX3 is evenly distributed throughout the cytoplasm at steady state. Consistent with this observation, HA-tagged DDX3 also localizes to the cytoplasm. RNAi of DDX3 in both human and Drosophila cells shows that DDX3 is required for cell viability. Moreover, using RNAi, we show that DDX3 is required for expression of protein from reporter constructs. In contrast, we did not detect a role for DDX3 in nuclear steps in gene expression. Further insight into the function of DDX3 came from the observation that its major interaction partner is the multi-component translation initiation factor eIF3. We conclude that a primary function for DDX3 is in protein translation, via an interaction with eIF3.

  13. A unique modification of the eukaryotic initiation factor 5A shows the presence of the complete hypusine pathway in Leishmania donovani.

    Directory of Open Access Journals (Sweden)

    Bhavna Chawla

    Full Text Available Deoxyhypusine hydroxylase (DOHH catalyzes the final step in the post-translational synthesis of an unusual amino acid hypusine (N(€-(4-amino-2-hydroxybutyl lysine, which is present on only one cellular protein, eukaryotic initiation factor 5A (eIF5A. We present here the molecular and structural basis of the function of DOHH from the protozoan parasite, Leishmania donovani, which causes visceral leishmaniasis. The L. donovani DOHH gene is 981 bp and encodes a putative polypeptide of 326 amino acids. DOHH is a HEAT-repeat protein with eight tandem repeats of α-helical pairs. Four conserved histidine-glutamate sequences have been identified that may act as metal coordination sites. A ~42 kDa recombinant protein with a His-tag was obtained by heterologous expression of DOHH in Escherichia coli. Purified recombinant DOHH effectively catalyzed the hydroxylation of the intermediate, eIF5A-deoxyhypusine (eIF5A-Dhp, in vitro. L. donovani DOHH (LdDOHH showed ~40.6% sequence identity with its human homolog. The alignment of L. donovani DOHH with the human homolog shows that there are two significant insertions in the former, corresponding to the alignment positions 159-162 (four amino acid residues and 174-183 (ten amino acid residues which are present in the variable loop connecting the N- and C-terminal halves of the protein, the latter being present near the substrate binding site. Deletion of the ten-amino-acid-long insertion decreased LdDOHH activity to 14% of the wild type recombinant LdDOHH. Metal chelators like ciclopirox olamine (CPX and mimosine significantly inhibited the growth of L. donovani and DOHH activity in vitro. These inhibitors were more effective against the parasite enzyme than the human enzyme. This report, for the first time, confirms the presence of a complete hypusine pathway in a kinetoplastid unlike eubacteria and archaea. The structural differences between the L. donovani DOHH and the human homolog may be exploited for

  14. Design, synthesis and structure-activity relationships of benzoxazinone-based factor Xa inhibitors.

    Science.gov (United States)

    Huang, Wenrong; Zhang, Penglie; Zuckett, Jingmei F; Wang, Lingyan; Woolfrey, John; Song, Yonghong; Jia, Zhaozhong J; Clizbe, Lane A; Su, Ting; Tran, Katherine; Huang, Brian; Wong, Paul; Sinha, Uma; Park, Gary; Reed, Andrea; Malinowski, John; Hollenbach, Stanley J; Scarborough, Robert M; Zhu, Bing-Yan

    2003-02-10

    A series of benzoxazinone derivatives was designed and synthesized as factor Xa inhibitors. We demonstrated that the naphthyl moiety in the aniline-based compounds 1 and 2 can be replaced with benzene-fused heterobicycles and biaryls to give factor Xa inhibitors with improved trypsin selectivity. The P4 modifications lead to monoamidines which are moderately active. The benzoxazinones 41-45 are potent against factor Xa, retain the improved trypsin selectivity of the corresponding aniline-based compounds, and show strong antithrombotic effect dose responsively.

  15. Trends of CD4 cell count levels at the initiation of antiretroviral therapy over time and factors associated with late initiation of antiretroviral therapy among Asian HIV-positive patients

    Science.gov (United States)

    Kiertiburanakul, Sasisopin; Boettiger, David; Lee, Man Po; Omar, Sharifah Fs; Tanuma, Junko; Ng, Oon Tek; Durier, Nicolas; Phanuphak, Praphan; Ditangco, Rossana; Chaiwarith, Romanee; Kantipong, Pacharee; Lee, Christopher Kc; Mustafa, Mahiran; Saphonn, Vonthanak; Ratanasuwan, Winai; Merati, Tuti Parwati; Kumarasamy, Nagalingeswaran; Wong, Wing Wai; Zhang, Fujie; Pham, Thanh Thuy; Pujari, Sanjay; Choi, Jun Yong; Yunihastuti, Evy; Sungkanuparph, Somnuek

    2014-01-01

    Introduction Although antiretroviral therapy (ART) has been rapidly scaled up in Asia, most HIV-positive patients in the region still present with late-stage HIV disease. We aimed to determine trends of pre-ART CD4 levels over time in Asian HIV-positive patients and to determine factors associated with late ART initiation. Methods Data from two regional cohort observational databases were analyzed for trends in median CD4 cell counts at ART initiation and the proportion of late ART initiation (CD4 cell counts ART initiation and mortality were determined. Results A total of 2737 HIV-positive ART-naïve patients from 22 sites in 13 Asian countries and territories were eligible. The overall median (IQR) CD4 cell count at ART initiation was 150 (46–241) cells/mm3. Median CD4 cell counts at ART initiation increased over time, from a low point of 115 cells/mm3 in 2008 to a peak of 302 cells/mm3 after 2011 (p for trend 0.002). The proportion of patients with late ART initiation significantly decreased over time from 79.1% before 2007 to 36.3% after 2011 (p for trend ART initiation were year of ART initiation (e.g. 2010 vs. before 2007; OR 0.40, 95% CI 0.27–0.59; pART initiation were late ART initiation (HR 2.13, 95% CI 1.19–3.79; p=0.010), sex (male vs. female; HR 2.12, 95% CI 1.31–3.43; p=0.002), age (≥51 vs. ≤30 years; HR 3.91, 95% CI 2.18–7.04; pART initiation among Asian patients significantly increases over time but the proportion of patients with late ART initiation is still significant. ART initiation at higher CD4 cell counts remains a challenge. Strategic interventions to increase earlier diagnosis of HIV infection and prompt more rapid linkage to ART must be implemented. PMID:24598459

  16. Fire Synthesis

    Indian Academy of Sciences (India)

    special infrastructure which require careful maintenance. In such situation fire synthesis is a simpler method that can be adopted for the bulk production of high purity .... reaction between Ti and B to form titanium boride. The reaction between titanium (fuel- electron donor) and boron (oxidiser-electron acceptor) once initiated ...

  17. The Translation Initiation Factor 1A (TheIF1A) fromTamarix hispidaIs Regulated by a Dof Transcription Factor and Increased Abiotic Stress Tolerance.

    Science.gov (United States)

    Yang, Guiyan; Yu, Lili; Wang, Yucheng; Wang, Chao; Gao, Caiqiu

    2017-01-01

    Eukaryotic translation initiation factor 1A ( eIF1A ) functions as an mRNA scanner and AUG initiation codon locator. However, few studies have clarified the role of eIF1A in abiotic stress. In this study, we cloned eIF1A ( TheIF1A ) from Tamarix hispida and found its expression to be induced by NaCl and polyethylene glycol (PEG) in roots, stems, and leaves. Compared to control, TheIF1A root expression was increased 187.63-fold when exposed to NaCl for 6 h, suggesting a potential abiotic stress response for this gene. Furthermore, transgenic tobacco plants overexpressing TheIF1A exhibited enhanced seed germination and a higher total chlorophyll content under salt and mannitol stresses. Increased superoxide dismutase, peroxidase, glutathione transferase and glutathione peroxidase activities, as well as decreased electrolyte leakage rates and malondialdehyde contents, were observed in TheIF1A -transgenic tobacco and T. hispida seedlings under salt and mannitol stresses. Histochemical staining suggested that TheIF1A improves reactive oxygen species (ROS) scavenging in plants. Moreover, TheIF1A may regulate expression of stress-related genes, including TOBLTP , GST , MnSOD , NtMPK9 , poxN1 , and CDPK15 . Moreover, a 1352-bp promoter fragment of TheIF1A was isolated, and cis -elements were identified. Yeast one-hybrid assays showed that ThDof can specifically bind to the Dof motif present in the promoter. In addition, ThDof showed expression patterns similar to those of TheIF1A under NaCl and PEG stresses. These findings suggest the potential mechanism and physiological roles of TheIF1A . ThDof may be an upstream regulator of TheIF1A , and TheIF1A may function as a stress response regulator to improve plant salt and osmotic stress tolerance via regulation of associated enzymes and ROS scavenging, thereby reducing cell damage under stress conditions.

  18. Epidermal transformation leads to increased perlecan synthesis with heparin-binding-growth-factor affinity

    DEFF Research Database (Denmark)

    Tapanadechopone, P; Tumova, S; Jiang, X

    2001-01-01

    . Despite this, the heparan sulphate of RT101- and JB6-derived perlecan bound fibroblast growth factor-1, -2, -4 and -7 and heparin-binding epidermal growth factor with similar affinity. Therefore abundant tumour-derived perlecan may support the angiogenic responses seen in vivo and be a key player......Perlecan, a proteoglycan of basement membrane and extracellular matrices, has important roles in both normal biological and pathological processes. As a result of its ability to store and protect growth factors, perlecan may have crucial roles in tumour-cell growth and invasion. Since...... the biological functions of different types of glycosaminoglycan vary with cellular origin and structural modifications, we analysed the expression and biological functions of perlecan produced by a normal epidermal cell line (JB6) and its transformed counterpart (RT101). Expression of perlecan in tumorigenic...

  19. Glycogen synthesis is induced in hypoxia by the hypoxia-inducible factor and promotes cancer cell survival

    Directory of Open Access Journals (Sweden)

    Joffrey ePelletier

    2012-02-01

    Full Text Available The hypoxia-inducible factor 1 (HIF-1, in addition to genetic and epigenetic changes, is largely responsible for alterations in cell metabolism in hypoxic tumor cells. This transcription factor not only favors cell proliferation through the metabolic shift from oxidative phosphorylation to glycolysis and lactic acid production but also stimulates nutrient supply by mediating adaptive survival mechanisms. In this study we showed that glycogen synthesis is enhanced in non-cancer and cancer cells when exposed to hypoxia, resulting in a large increase in glycogen stores. Furthermore, we demonstrated that the mRNA and protein levels of the first enzyme of glycogenesis, phosphoglucomutase1 (PGM1, were increased in hypoxia. We showed that induction of glycogen storage as well as PGM1 expression were dependent on HIF-1 and HIF-2. We established that hypoxia-induced glycogen stores are rapidly mobilized in cells that are starved of glucose. Glycogenolysis allows these hypoxia-preconditioned cells to confront and survive glucose deprivation. In contrast normoxic control cells exhibit a high rate of cell death following glucose removal. These findings point to the important role of hypoxia and HIF in inducing mechanisms of rapid adaptation and survival in response to a decrease in oxygen tension. We propose that a decrease in pO2 acts as an alarm that prepares the cells to face subsequent nutrient depletion and to survive.

  20. An isoform of eukaryotic initiation factor 4E from Chrysanthemum morifolium interacts with Chrysanthemum virus B coat protein.

    Science.gov (United States)

    Song, Aiping; Lou, Wanghuai; Jiang, Jiafu; Chen, Sumei; Sun, Zuxia; Guan, Zhiyong; Fang, Weimin; Teng, Nianjun; Chen, Fadi

    2013-01-01

    Eukaryotic translation initiation factor 4E (eIF4E) plays an important role in plant virus infection as well as the regulation of gene translation. Here, we describe the isolation of a cDNA encoding CmeIF(iso)4E (GenBank accession no. JQ904592), an isoform of eIF4E from chrysanthemum, using RACE PCR. We used the CmeIF(iso)4E cDNA for expression profiling and to analyze the interaction between CmeIF(iso)4E and the Chrysanthemum virus B coat protein (CVBCP). Multiple sequence alignment and phylogenetic tree analysis showed that the sequence similarity of CmeIF(iso)4E with other reported plant eIF(iso)4E sequences varied between 69.12% and 89.18%, indicating that CmeIF(iso)4E belongs to the eIF(iso)4E subfamily of the eIF4E family. CmeIF(iso)4E was present in all chrysanthemum organs, but was particularly abundant in the roots and flowers. Confocal microscopy showed that a transiently transfected CmeIF(iso)4E-GFP fusion protein distributed throughout the whole cell in onion epidermis cells. A yeast two hybrid assay showed CVBCP interacted with CmeIF(iso)4E but not with CmeIF4E. BiFC assay further demonstrated the interaction between CmeIF(iso)4E and CVBCP. Luminescence assay showed that CVBCP increased the RLU of Luc-CVB, suggesting CVBCP might participate in the translation of viral proteins. These results inferred that CmeIF(iso)4E as the cap-binding subunit eIF(iso)4F may be involved in Chrysanthemum Virus B infection in chrysanthemum through its interaction with CVBCP in spatial.

  1. Eukaryotic translation initiation factor 5A (eIF5A) is essential for HIF-1α activation in hypoxia

    Energy Technology Data Exchange (ETDEWEB)

    Tariq, Mohammad [Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Graduate School of Science and Engineering, Saitama University, 645 Shimo-Okubo, Sakura-ku, Saitama 338-8570 (Japan); Ito, Akihiro, E-mail: akihiro-i@riken.jp [Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Japan Agency for Medical Research and Development, AMED-CREST, 1-7-1 Otemachi, Chiyoda-ku, Tokyo, 100-0004 (Japan); Ishfaq, Muhammad; Bradshaw, Elliot [Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Graduate School of Science and Engineering, Saitama University, 645 Shimo-Okubo, Sakura-ku, Saitama 338-8570 (Japan); Yoshida, Minoru [Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Graduate School of Science and Engineering, Saitama University, 645 Shimo-Okubo, Sakura-ku, Saitama 338-8570 (Japan); Japan Agency for Medical Research and Development, AMED-CREST, 1-7-1 Otemachi, Chiyoda-ku, Tokyo, 100-0004 (Japan)

    2016-02-05

    The eukaryotic initiation factor 5A (eIF5A) is an essential protein involved in translation elongation and cell proliferation. eIF5A undergoes several post-translational modifications including hypusination and acetylation. Hypusination is indispensable for the function of eIF5A. On the other hand, the precise function of acetylation remains unknown, but it may render the protein inactive since hypusination blocks acetylation. Here, we report that acetylation of eIF5A increases under hypoxia. During extended hypoxic periods an increase in the level of eIF5A acetylation correlated with a decrease in HIF-1α, suggesting involvement of eIF5A activity in HIF-1α expression under hypoxia. Indeed, suppression of eIF5A by siRNA oligo-mediated knockdown or treatment with GC7, a deoxyhypusine synthase inhibitor, led to significant reduction of HIF-1α activity. Furthermore, knockdown of eIF5A or GC7 treatment reduced tumor spheroid formation with a concomitant decrease in HIF-1α expression. Our results suggest that functional, hypusinated eIF5A is necessary for HIF-1α expression during hypoxia and that eIF5A is an attractive target for cancer therapy. - Highlights: • Hypoxia induces acetylation of eIF5A. • Active eIF5A is necessary for HIF-1α activation in hypoxia. • Active eIF5A is important for tumor spheroid growth.

  2. The translation initiation factor DAP5 promotes IRES-driven translation of p53 mRNA.

    Science.gov (United States)

    Weingarten-Gabbay, S; Khan, D; Liberman, N; Yoffe, Y; Bialik, S; Das, S; Oren, M; Kimchi, A

    2014-01-30

    Translational regulation of the p53 mRNA can determine the ratio between p53 and its N-terminal truncated isoforms and therefore has a significant role in determining p53-regulated signaling pathways. Although its importance in cell fate decisions has been demonstrated repeatedly, little is known about the regulatory mechanisms that determine this ratio. Two internal ribosome entry sites (IRESs) residing within the 5'UTR and the coding sequence of p53 mRNA drive the translation of full-length p53 and Δ40p53 isoform, respectively. Here, we report that DAP5, a translation initiation factor shown to positively regulate the translation of various IRES containing mRNAs, promotes IRES-driven translation of p53 mRNA. Upon DAP5 depletion, p53 and Δ40p53 protein levels were decreased, with a greater effect on the N-terminal truncated isoform. Functional analysis using bicistronic vectors driving the expression of a reporter gene from each of these two IRESs indicated that DAP5 preferentially promotes translation from the second IRES residing in the coding sequence. Furthermore, p53 mRNA expressed from a plasmid carrying this second IRES was selectively shifted to lighter polysomes upon DAP5 knockdown. Consequently, Δ40p53 protein levels and the subsequent transcriptional activation of the 14-3-3σ gene, a known target of Δ40p53, were strongly reduced. In addition, we show here that DAP5 interacts with p53 IRES elements in in vitro and in vivo binding studies, proving for the first time that DAP5 directly binds a target mRNA. Thus, through its ability to regulate IRES-dependent translation of the p53 mRNA, DAP5 may control the ratio between different p53 isoforms encoded by a single mRNA.

  3. An isoform of eukaryotic initiation factor 4E from Chrysanthemum morifolium interacts with Chrysanthemum virus B coat protein.

    Directory of Open Access Journals (Sweden)

    Aiping Song

    Full Text Available BACKGROUND: Eukaryotic translation initiation factor 4E (eIF4E plays an important role in plant virus infection as well as the regulation of gene translation. METHODOLOGY/PRINCIPAL FINDINGS: Here, we describe the isolation of a cDNA encoding CmeIF(iso4E (GenBank accession no. JQ904592, an isoform of eIF4E from chrysanthemum, using RACE PCR. We used the CmeIF(iso4E cDNA for expression profiling and to analyze the interaction between CmeIF(iso4E and the Chrysanthemum virus B coat protein (CVBCP. Multiple sequence alignment and phylogenetic tree analysis showed that the sequence similarity of CmeIF(iso4E with other reported plant eIF(iso4E sequences varied between 69.12% and 89.18%, indicating that CmeIF(iso4E belongs to the eIF(iso4E subfamily of the eIF4E family. CmeIF(iso4E was present in all chrysanthemum organs, but was particularly abundant in the roots and flowers. Confocal microscopy showed that a transiently transfected CmeIF(iso4E-GFP fusion protein distributed throughout the whole cell in onion epidermis cells. A yeast two hybrid assay showed CVBCP interacted with CmeIF(iso4E but not with CmeIF4E. BiFC assay further demonstrated the interaction between CmeIF(iso4E and CVBCP. Luminescence assay showed that CVBCP increased the RLU of Luc-CVB, suggesting CVBCP might participate in the translation of viral proteins. CONCLUSIONS/SIGNIFICANCE: These results inferred that CmeIF(iso4E as the cap-binding subunit eIF(iso4F may be involved in Chrysanthemum Virus B infection in chrysanthemum through its interaction with CVBCP in spatial.

  4. Prognostic factors and survival according to tumour subtype in women presenting with breast cancer brain metastases at initial diagnosis.

    Science.gov (United States)

    Leone, José Pablo; Leone, Julieta; Zwenger, Ariel Osvaldo; Iturbe, Julián; Leone, Bernardo Amadeo; Vallejo, Carlos Teodoro

    2017-03-01

    The presence of brain metastases at the time of initial breast cancer diagnosis (BMIBCD) is uncommon. Hence, the prognostic assessment and management of these patients is very challenging. The aim of this study was to analyse the influence of tumour subtype compared with other prognostic factors in the survival of patients with BMIBCD. We evaluated women with BMIBCD, reported to Surveillance, Epidemiology and End Results program from 2010 to 2013. Patients with other primary malignancy were excluded. Univariate and multivariate analyses were performed to determine the effects of each variable on overall survival (OS). We included 740 patients. Median OS for the whole population was 10 months, and 20.7% of patients were alive at 36 months. Tumour subtype distribution was: 46.6% hormone receptor (HR)+/HER2-, 17% HR+/HER2+, 14.1% HR-/HER2+ and 22.3% triple-negative. Univariate analysis showed that the presence of liver metastases, lung metastases and triple-negative patients (median OS 6 months) had worse prognosis. The HR+/HER2+ subtype had the longest OS with a median of 22 months. In multivariate analysis, older age (hazard ratio 1.8), lobular histology (hazard ratio 2.08), triple-negative subtype (hazard ratio 2.25), liver metastases (hazard ratio 1.6) and unmarried patients (hazard ratio 1.39) had significantly shorter OS. Although the prognosis of patients with BMIBCD is generally poor, 20.7% were still alive 3 years after the diagnosis. There were substantial differences in OS according to tumour subtype. In addition to tumour subtype, other independent predictors of OS are age at diagnosis, marital status, histology and liver metastases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Autophosphorylation of heme-regulated eukaryotic initiation factor 2α kinase and the role of the modification in catalysis.

    Science.gov (United States)

    Igarashi, Jotaro; Sasaki, Takehiko; Kobayashi, Noriko; Yoshioka, Shinji; Matsushita, Miyuki; Shimizu, Toru

    2011-04-01

    Heme-regulated eukaryotic initiation factor 2α (eIF2α) kinase (HRI), functions in response to heme shortage in reticulocytes and aids in the maintenance of a heme:globin ratio of 1:1. Under normal conditions, heme binds to HRI and blocks its function. However, during heme shortage, heme dissociates from the protein and autophosphorylation subsequently occurs. Autophosphorylation comprises a preliminary critical step before the execution of the intrinsic function of HRI; specifically, phosphorylation of Ser-51 of eIF2α to inhibit translation of the globin protein. The present study indicates that dephosphorylated mouse HRI exhibits strong intramolecular interactions (between the N-terminal and C-terminal domains) compared to phosphorylated HRI. It is therefore suggested that autophosphorylation reduces the intramolecular interaction, which induces irreversible catalytic flow to the intrinsic eIF2α kinase activity after heme dissociates from the protein. With the aid of MS, we identified 33 phosphorylated sites in mouse HRI overexpressed in Escherichia coli. Phosphorylated sites at Ser, Thr and Tyr were predominantly localized within the kinase insertion region (16 sites) and kinase domain (12 sites), whereas the N-terminal domain contained five sites. We further generated 30 enzymes with mutations at the phosphorylated residues and examined their catalytic activities. The activities of Y193F, T485A and T490A mutants were significantly lower than that of wild-type protein, whereas the other mutant proteins displayed essentially similar activity. Accordingly, we suggest that Tyr193, Thr485 and Thr490 are essential residues in the catalysis. © 2011 The Authors Journal compilation © 2011 FEBS.

  6. Insulin-like growth factor I enhances collagen synthesis in engineered human tendon tissue

    DEFF Research Database (Denmark)

    Herchenhan, Andreas; Bayer, Monika L.; Eliasson, Pernilla

    2015-01-01

    OBJECTIVE: Isolated human tendon cells form 3D tendon constructs that demonstrate collagen fibrillogenesis and feature structural similarities to tendon when cultured under tensile load. The exact role of circulating growth factors for collagen formation in tendon is sparsely examined. We investi...

  7. Motivating factors for seeking cosmetic surgery: a synthesis of the literature.

    Science.gov (United States)

    Haas, Cynthia Figueroa; Champion, Angela; Secor, Danielle

    2008-01-01

    The fascination in physical beauty is becoming more and more prevalent in today's society. Beauty in American culture is defined by the media through magazines, television, and music. The perfect career, the perfect family, social status, and high self-esteem all revolve around having an impeccable figure. Research shows that 94% of the covers of women's magazines showcase a woman with a thin physique (A. R., Malkin, K., Wornian, & J. C. Chrisler, 1999). Therefore, it is not surprising that year after year, millions of people elect for cosmetic surgery. According to the , approximately 11.7 million cosmetic surgical and nonsurgical procedures were performed and Americans spent $13.2 billion on these procedures. This is a 457% increase since 1997. As the demand for elective cosmetic surgery continues to rise, it is important for healthcare employees to recognize the motive behind the decision to seek cosmetic surgery. The purpose of this literature review project was to ascertain those factors that influence or motivate patients to seek cosmetic surgery. This project investigated physical, psychiatric, and psychosocial factors associated with individuals who undergo elective cosmetic surgery. It has been shown that the motivation for cosmetic surgery is based on a combination of psychological and emotional factors. Researchers surmise that body image, teasing history, and self-esteem were associated with motivational factors for those patients who elected to seek cosmetic surgery (T. Soest, I. L. Kvalem, K. C. Skolleborg, & H. E. Roald, 2006). In addition, the researchers concluded that body dysmorphic disorder, education, and culture are also predicting factors in the decision to have cosmetic surgery.

  8. Changes in the strength of peer influence and cultural factors on substance use initiation between late adolescence and emerging adulthood in a Hispanic sample.

    Science.gov (United States)

    Grigsby, Timothy J; Forster, Myriam; Soto, Daniel W; Unger, Jennifer B

    2017-01-01

    We examine whether peer substance use and cultural factors differentially influence the initiation of tobacco, alcohol, and marijuana use in adolescence and emerging adulthood (EA) among a community-based sample of Hispanics. Participants provided data in 11th grade (M = 16.8 years old, SD = 0.54) and emerging adulthood (M = 20.3 years old, SD = 0.6). Peer tobacco use had a stronger association with initiation of tobacco use in emerging adulthood (OR = 1.46, 95% CI = 1.13, 1.89) than in adolescence (OR = 1.20, 95% CI = 1.03, 1.40), but this pattern was not observed with initiation of alcohol or marijuana use. Cultural orientation is associated with initiation of tobacco use during EA but not with initiation of alcohol or marijuana use.

  9. Role of epidermal growth factor receptor activation in regulating mucin synthesis

    Directory of Open Access Journals (Sweden)

    Nadel Jay A

    2001-02-01

    Full Text Available Abstract Healthy individuals have few goblet cells in their airways, but in patients with hypersecretory diseases goblet-cell upregulation results in mucus hypersecretion, airway plugging, and death. Multiple stimuli produce hypersecretion via epidermal growth factor receptor (EGFR expression and activation, causing goblet-cell metaplasia from Clara cells by a process of cell differentiation. These cells are also believed to be the cells of origin of non-small-cell lung cancer, but this occurs via cell multiplication. The mechanisms that determine which pathway is chosen are critical but largely unknown. Although no effective therapy exists for hypersecretion at present, the EGFR cascade suggests methods for effective therapeutic intervention.

  10. The rice eukaryotic translation initiation factor 3 subunit f (OseIF3f is involved in microgametogenesis

    Directory of Open Access Journals (Sweden)

    Qi eLi

    2016-04-01

    Full Text Available Microgametogenesis is the postmeiotic pollen developmental phase when unicellular microspores develop into mature tricellular pollen. In rice, microgametogenesis can influence grain yields to a great degree because pollen abortion occurs more easily during microgametogenesis than during other stages of pollen development. However, our knowledge of the genes involved in microgametogenesis in rice remains limited. Due to the dependence of pollen development on the regulatory mechanisms of protein expression, we identified the encoding gene of the eukaryotic translation initiation factor 3, subunit f in Oryza sativa (OseIF3f. Immunoprecipitation combined with mass spectrometry confirmed that OseIF3f was a subunit of rice eIF3, which consisted of at least 12 subunits including eIF3a, eIF3b, eIF3c, eIF3d, eIF3e, eIF3f, eIF3g, eIF3h, eIF3i, eIF3k, eIF3l and eIF3m. OseIF3f showed high mRNA levels in immature florets and is highly abundant in developing anthers. Subcellular localization analysis showed that OseIF3f was localized to the cytosol and the endoplasmic reticulum in rice root cells. We further analyzed the biological function of OseIF3f using the double-stranded RNA-mediated interference (RNAi approach. The OseIF3f-RNAi lines grew normally at the vegetative stage but displayed a large reduction in seed production and pollen viability, which is associated with the down-regulation of OseIF3f. Further cytological observations of pollen development revealed that the OseIF3f-RNAi lines showed no obvious abnormalities at the male meiotic stage and the unicellular microspore stage. However, compared to the wild type, OseIF3f-RNAi lines contained a higher percentage of arrested unicellular pollen at the bicellular stage and a higher percentage of arrested unicellular and bicellular pollen, and aborted pollen at the tricellular stage. These results indicate that OseIF3f plays a role in microgametogenesis.

  11. Factors Influencing Farmers’ Adoption of Best Management Practices: A Review and Synthesis

    Directory of Open Access Journals (Sweden)

    Tingting Liu

    2018-02-01

    Full Text Available Best management practices (BMPs for reducing agricultural non-point source pollution are widely available. However, agriculture remains a major global contributor to degradation of waters because farmers often do not adopt BMPs. To improve water quality, it is necessary to understand the factors that influence BMP adoption by farmers. We review the findings of BMP adoption studies from both developed and developing countries, published after (or otherwise not included in two major literature reviews from 2007 and 2008. We summarize the study locations, scales, and BMPs studied; the analytical methods used; the factors evaluated; and the directionality of each factor’s influence on BMP adoption. We then present a conceptual framework for BMP adoption decisions that emphasizes the importance of scale, the tailoring or targeting of information and incentives, and the importance of expected farm profits. We suggest that future research directions should focus on study scale, on measuring and modeling of adoption as a continuous process, and on incorporation of social norms and uncertainty into decision-making. More research is needed on uses of social media and market recognition approaches (such as certificate schemes and consumer labeling to influence BMP adoption.

  12. Contributing factors of frequent use of the emergency department: A synthesis.

    Science.gov (United States)

    Burns, Timothy R

    2017-11-01

    Overcrowding in emergency departments is an issue that has a negative impact worldwide. As attendance in emergency departments has increased, the ability to provide critical services to patients suffering from actual medical emergencies in a timely manner has decreased as these departments are many times at or over capacity. One patient population whose negative influence has been researched with regard to their impact on the overcrowding issue is that of the frequent user. A search of two electronic databases was conducted to identify factors that frequent users state as their reasoning for using an emergency department. Peer reviewed articles in English were searched for in CINAHL Plus and PubMed, as well as a review of reference lists. A review of the literature identified two predominant factors related to frequent users in the emergency department: a lack of awareness of medical necessity and issues of access. To address the frequent users in emergency departments, implications for practice need to be explored and implemented. Implications for practice include education of medical necessity for the frequent users, expansion of the pre-hospital role in primary care and inappropriate use prevention, and improvement of access to alternative healthcare services. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Mechanism governing heme synthesis reveals a GATA factor/heme circuit that controls differentiation.

    Science.gov (United States)

    Tanimura, Nobuyuki; Miller, Eli; Igarashi, Kazuhiko; Yang, David; Burstyn, Judith N; Dewey, Colin N; Bresnick, Emery H

    2016-02-01

    Metal ion-containing macromolecules have fundamental roles in essentially all biological processes throughout the evolutionary tree. For example, iron-containing heme is a cofactor in enzyme catalysis and electron transfer and an essential hemoglobin constituent. To meet the intense demand for hemoglobin assembly in red blood cells, the cell type-specific factor GATA-1 activates transcription of Alas2, encoding the rate-limiting enzyme in heme biosynthesis, 5-aminolevulinic acid synthase-2 (ALAS-2). Using genetic editing to unravel mechanisms governing heme biosynthesis, we discovered a GATA factor- and heme-dependent circuit that establishes the erythroid cell transcriptome. CRISPR/Cas9-mediated ablation of two Alas2 intronic cis elements strongly reduces GATA-1-induced Alas2 transcription, heme biosynthesis, and surprisingly, GATA-1 regulation of other vital constituents of the erythroid cell transcriptome. Bypassing ALAS-2 function in Alas2 cis element-mutant cells by providing its catalytic product 5-aminolevulinic acid rescues heme biosynthesis and the GATA-1-dependent genetic network. Heme amplifies GATA-1 function by downregulating the heme-sensing transcriptional repressor Bach1 and via a Bach1-insensitive mechanism. Through this dual mechanism, heme and a master regulator collaborate to orchestrate a cell type-specific transcriptional program that promotes cellular differentiation. © 2015 The Authors.

  14. Prospective Analysis of the Influence of Sport and Educational Factors on the Prevalence and Initiation of Smoking in Older Adolescents from Croatia

    OpenAIRE

    Natasa Zenic; Djivo Ban; Sanja Jurisic; Mladen Cubela; Jelena Rodek; Ljerka Ostojic; Mario Jelicic; Antonino Bianco; Damir Sekulic

    2017-01-01

    The prevalence of smoking among Croatian adolescents is alarmingly high, but no previous study has prospectively examined the sport- and academic-factors associated with smoking and smoking initiation. This study aimed to prospectively examine the associations between scholastic (educational) achievement and sport factors and smoking in 16- to 18-year-old adolescents. This two-year prospective cohort study included 644 adolescents who were 16 years of age at baseline (46% females). Baseline t...

  15. Rational Design and Synthesis of Efficient Sunscreens To Boost the Solar Protection Factor.

    Science.gov (United States)

    Losantos, Raúl; Funes-Ardoiz, Ignacio; Aguilera, José; Herrera-Ceballos, Enrique; García-Iriepa, Cristina; Campos, Pedro J; Sampedro, Diego

    2017-03-01

    Skin cancer incidence has been increasing in the last decades, but most of the commercial formulations used as sunscreens are designed to protect only against solar erythema. Many of the active components present in sunscreens show critical weaknesses, such as low stability and toxicity. Thus, the development of more efficient components is an urgent health necessity and an attractive industrial target. We have rationally designed core moieties with increased photoprotective capacities and a new energy dissipation mechanism. Using these scaffolds, we have synthesized a series of compounds with tunable properties suitable for their use in sunscreens, and enhanced properties in terms of stability, light energy dissipation, and toxicity. Moreover, some representative compounds were included in final sunscreen formulations and a relevant solar protection factor boost was measured. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Analyses of factors affecting nickel ferrite nanoparticles synthesis in ultrasound-assisted aqueous solution ball milling.

    Science.gov (United States)

    Yuan, Zhuang; Chen, Zhen-hua; Chen, Ding; Kang, Zhi-tao

    2015-01-01

    Ball milling experiments were conducted with and without ultrasound wave assistance in deionized water using NiCO3·2Ni(OH)2·4H2O as raw materials. In the reaction process of NiFe2O4 prepared by ultrasound-assisted aqueous solution ball milling, some influencing factors including raw materials, ultrasonic frequency, ball to powder ratio and liquid level were changed. Samples were characterized by X-ray diffraction, fluorescence measurements and electroconductivity detections. The results indicate that more hydroxyl radicals and ions can be generated under the coupling effect of ultrasonic and ball milling. The fluorescence measurements and electroconductivity detections also reflect the reaction speed, allowing for optimal parameters to be determined. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Microglia protect neurons against ischemia by synthesis of tumor necrosis factor

    DEFF Research Database (Denmark)

    Lambertsen, Kate Lykke; Clausen, Bettina Hjelm; Babcock, Alicia

    2009-01-01

    Microglia and infiltrating leukocytes are considered major producers of tumor necrosis factor (TNF), which is a crucial player in cerebral ischemia and brain inflammation. We have identified a neuroprotective role for microglial-derived TNF in cerebral ischemia in mice. We show that cortical....... Additional analysis demonstrating that BM-chimeric TNF-KO mice grafted with wild-type BM cells developed larger infarcts than BM-chimeric wild-type mice grafted with TNF-KO BM cells provided evidence that the neuroprotective effect of TNF was attributable to microglial- not leukocyte-derived TNF. In addition......, observation of increased infarction in TNF-p55 receptor (TNF-p55R)-KO mice compared with TNF-p75R and wild-type mice suggested that microglial-derived TNF exerts neuroprotective effects through TNF-p55R. We finally report that TNF deficiency is associated with reduced microglial population size and Toll...

  18. Synthesis and characterization of 18F-labeled active site inhibited factor VII (ASIS)

    DEFF Research Database (Denmark)

    Erlandsson, Maria; Nielsen, Carsten Haagen; Jeppesen, Troels Elmer

    2015-01-01

    column. The radiochemical yield was 25 ± 6%, the radiochemical purity was >97%, and the pseudospecific radioactivity was 35 ± 9 GBq/µmol. The binding efficacy was evaluated in pull-down experiments, which monitored the binding of unlabeled ASIS and [18F]ASIS to TF and to a specific anti-factor VII...... antibody (F1A2-mAb). No significant difference in binding efficacy between [18F]ASIS and ASIS could be detected. Furthermore, [18F]ASIS was relatively stable in vitro and in vivo in mice. In conclusion, [18F]ASIS has for the first time been successfully synthesized as a possible positron emission...

  19. Translation initiation factors eIF3 and HCR1 control translation termination and stop codon read-through in yeast cells

    Czech Academy of Sciences Publication Activity Database

    Beznosková, P.; Cuchalová, Lucie; Wagner, S.; Shoemaker, Ch. J.; Gunišová, S.; von der Haar, T.; Valášek, L. S.

    2013-01-01

    Roč. 9, č. 11 (2013), e1003962_1-e1003962_17 ISSN 1553-7404 Institutional support: RVO:61389013 Keywords : translation initiation * translation termination * eIF3 Subject RIV: CD - Macromolecular Chemistry Impact factor: 8.167, year: 2013

  20. The relative contribution of genes and environment to alcohol use in early adolescents: are similar factors related to initiation of alcohol use and frequency of drinking?

    NARCIS (Netherlands)

    Poelen, Evelien A. P.; Derks, Eske M.; Engels, Rutger C. M. E.; van Leeuwe, Jan F. J.; Scholte, Ron H. J.; Willemsen, Gonneke; Boomsma, Dorret I.

    2008-01-01

    The present study assessed the relative contribution of genes and environment to individual differences in initiation of alcohol use and frequency of drinking among early adolescents and examined the extent to which the same genetic and environmental factors influence both individual differences in

  1. Investigation of the translation-initiation factor IF2 gene, infB, as a tool to study the population structure of Streptococcus agalactiae

    DEFF Research Database (Denmark)

    Hedegaard, J; Hauge, M; Fage-Larsen, J

    2000-01-01

    The sequence of infB, encoding the prokaryotic translation-initiation factor 2 (IF2), was determined in eight strains of Streptococcus agalactiae (group B streptococcus) and an alignment revealed limited intraspecies diversity within S. agalactiae. The amino acid sequence of IF2 from S. agalactiae...

  2. The Depression Initiative. Description of a collaborative care model for depression and of the factors influencing its implementation in the primary care setting in the Netherlands

    NARCIS (Netherlands)

    Jong, de F.J.; Steenbergen-Weijenburg, van K.M.; Huijbregts, K.M.L.; Vlasveld, M.C.; Marwijk, van H.W.J.; Beekman, A.T.F.; Feltz - Cornelis, van der C.M.

    2009-01-01

    BACKGROUND: In the Depression Initiative, a promising collaborative care model for depression that was developed in the US was adapted for implementation in the Netherlands. AIM: Description of a collaborative care model for major depressive disorder (MDD) and of the factors influencing its

  3. The transcription factor EGR1 localizes to the nucleolus and is linked to suppression of ribosomal precursor synthesis.

    Directory of Open Access Journals (Sweden)

    Donatella Ponti

    Full Text Available EGR1 is an immediate early gene with a wide range of activities as transcription factor, spanning from regulation of cell growth to differentiation. Numerous studies show that EGR1 either promotes the proliferation of stimulated cells or suppresses the tumorigenic growth of transformed cells. Upon interaction with ARF, EGR1 is sumoylated and acquires the ability to bind to specific targets such as PTEN and in turn to regulate cell growth. ARF is mainly localized to the periphery of nucleolus where is able to negatively regulate ribosome biogenesis. Since EGR1 colocalizes with ARF under IGF-1 stimulation we asked the question of whether EGR1 also relocate to the nucleolus to interact with ARF. Here we show that EGR1 colocalizes with nucleolar markers such as fibrillarin and B23 in the presence of ARF. Western analysis of nucleolar extracts from HeLa cells was used to confirm the presence of EGR1 in the nucleolus mainly as the 100 kDa sumoylated form. We also show that the level of the ribosomal RNA precursor 47S is inversely correlated to the level of EGR1 transcripts. The EGR1 iseffective to regulate the synthesis of the 47S rRNA precursor. Then we demonstrated that EGR1 binds to the Upstream Binding Factor (UBF leading us to hypothesize that the regulating activity of EGR1 is mediated by its interaction within the transcriptional complex of RNA polymerase I. These results confirm the presence of EGR1 in the nucleolus and point to a role for EGR1 in the control of nucleolar metabolism.

  4. Integration Host Factor (IHF binds to the promoter region of the phtD operon involved in phaseolotoxin synthesis in P. syringae pv. phaseolicola NPS3121

    Directory of Open Access Journals (Sweden)

    Álvarez-Morales Ariel

    2011-05-01

    Full Text Available Abstract Background Pseudomonas syringae pv. phaseolicola, the causal agent of halo blight disease in beans, produces a toxin known as phaseolotoxin, in whose synthesis participate a group of genes organized within the genome in a region known as the "Pht cluster". This region, which is thought to have been acquired by horizontal gene transfer, includes 5 transcriptional units, two monocistronic (argK, phtL and three polycistronic (phtA, phtD, phtM, whose expression is temperature dependent. So far, the regulatory mechanisms involved in phaseolotoxin synthesis have not been elucidated and the only well-established fact is the requirement of low temperatures for its synthesis. In this work, we searched for regulatory proteins that could be involved in phaseolotoxin synthesis, focusing on the regulation of the phtD operon. Results In this study we identified the global regulator IHF (Integration Host Factor, which binds to the promoter region of the phtD operon, exerting a negative effect on the expression of this operon. This is the first regulatory protein identified as part of the phaseolotoxin synthesis system. Our findings suggest that the Pht cluster was similarly regulated in the ancestral cluster by IHF or similar protein, and integrated into the global regulatory mechanism of P. syringae pv. phaseolicola, after the horizontal gene transfer event by using the host IHF protein. Conclusion This study identifies the IHF protein as one element involved in the regulation of phaseolotoxin synthesis in P. syringae pv. phaseolicola NPS3121 and provides new insights into the regulatory mechanisms involved in phaseolotoxin production.

  5. Which providers can bridge the health literacy gap in lifestyle risk factor modification education: a systematic review and narrative synthesis

    Directory of Open Access Journals (Sweden)

    Dennis Sarah

    2012-05-01

    Full Text Available Abstract Background People with low health literacy may not have the capacity to self-manage their health and prevent the development of chronic disease through lifestyle risk factor modification. The aim of this narrative synthesis is to determine the effectiveness of primary healthcare providers in developing health literacy of patients to make SNAPW (smoking, nutrition, alcohol, physical activity and weight lifestyle changes. Methods Studies were identified by searching Medline, Embase, Cochrane Library, CINAHL, Joanna Briggs Institute, Psychinfo, Web of Science, Scopus, APAIS, Australian Medical Index, Community of Science and Google Scholar from 1 January 1985 to 30 April 2009. Health literacy and related concepts are poorly indexed in the databases so a list of text words were developed and tested for use. Hand searches were also conducted of four key journals. Studies published in English and included males and females aged 18 years and over with at least one SNAPW risk factor for the development of a chronic disease. The interventions had to be implemented within primary health care, with an aim to influence the health literacy of patients to make SNAPW lifestyle changes. The studies had to report an outcome measure associated with health literacy (knowledge, skills, attitudes, self efficacy, stages of change, motivation and patient activation and SNAPW risk factor. The definition of health literacy in terms of functional, communicative and critical health literacy provided the guiding framework for the review. Results 52 papers were included that described interventions to address health literacy and lifestyle risk factor modification provided by different health professionals. Most of the studies (71%, 37/52 demonstrated an improvement in health literacy, in particular interventions of a moderate to high intensity. Non medical health care providers were effective in improving health literacy. However this was confounded by intensity of

  6. Which providers can bridge the health literacy gap in lifestyle risk factor modification education: a systematic review and narrative synthesis.

    Science.gov (United States)

    Dennis, Sarah; Williams, Anna; Taggart, Jane; Newall, Anthony; Denney-Wilson, Elizabeth; Zwar, Nicholas; Shortus, Tim; Harris, Mark F

    2012-05-28

    People with low health literacy may not have the capacity to self-manage their health and prevent the development of chronic disease through lifestyle risk factor modification. The aim of this narrative synthesis is to determine the effectiveness of primary healthcare providers in developing health literacy of patients to make SNAPW (smoking, nutrition, alcohol, physical activity and weight) lifestyle changes. Studies were identified by searching Medline, Embase, Cochrane Library, CINAHL, Joanna Briggs Institute, Psychinfo, Web of Science, Scopus, APAIS, Australian Medical Index, Community of Science and Google Scholar from 1 January 1985 to 30 April 2009. Health literacy and related concepts are poorly indexed in the databases so a list of text words were developed and tested for use. Hand searches were also conducted of four key journals. Studies published in English and included males and females aged 18 years and over with at least one SNAPW risk factor for the development of a chronic disease. The interventions had to be implemented within primary health care, with an aim to influence the health literacy of patients to make SNAPW lifestyle changes. The studies had to report an outcome measure associated with health literacy (knowledge, skills, attitudes, self efficacy, stages of change, motivation and patient activation) and SNAPW risk factor.The definition of health literacy in terms of functional, communicative and critical health literacy provided the guiding framework for the review. 52 papers were included that described interventions to address health literacy and lifestyle risk factor modification provided by different health professionals. Most of the studies (71%, 37/52) demonstrated an improvement in health literacy, in particular interventions of a moderate to high intensity.Non medical health care providers were effective in improving health literacy. However this was confounded by intensity of intervention. Provider barriers impacted on their

  7. Initiation of protein synthesis by a labeled derivative of the Lactobacillus casei DN-114 001 strain during transit from the stomach to the cecum in mice harboring human microbiota.

    Science.gov (United States)

    Oozeer, R; Mater, D D G; Goupil-Feuillerat, N; Corthier, G

    2004-12-01

    Although studies on the survival of bacteria in the digestive tract have been reported in the literature, little data are available on the physiological adaptation of probiotics to the digestive environment. In previous work, a transcriptional fusion system (i.e., luciferase genes under the control of a deregulated promoter) was used to demonstrate that a derivative of the Lactobacillus casei DN-114 001 strain, ingested in a fermented milk and thus exhibiting initially a very weak metabolic activity, synthesized proteins de novo after its transit in the digestive tract of mice harboring human microbiota (known as human-microbiota-associated mice). With the same genetic system and animal model, we here investigate for the first time the ability of L. casei to reinitiate synthesis in the different digestive tract compartments. In this study, most ingested L. casei cells transited from the stomach to the duodenum-jejunum within 1 h postingestion. No luciferase activity was observed in these digestive tract compartments after the first hour. At later times, the bulk of bacteria had transited to the ileum and the cecum. Luciferase synthesis was detected between 1.5 and 2.0 h postingestion at the ileal level and from 1.5 h to at least 6.0 h postingestion in the cecum, where the activity remained at a maximum level. These results demonstrate that ingested L. casei (derivative of the DN-114 001 strain) administered via a fermented milk has already reinitiated protein synthesis when it reaches the ileal and cecal compartments.

  8. Calcitriol enhances fat synthesis factors and calpain activity in co-cultured cells.

    Science.gov (United States)

    Choi, Hyuck; Myung, Kyuho

    2014-08-01

    We have conducted an in vitro experiment to determine whether calcitriol can act as a fat synthesizer and/or meat tenderizer when skeletal muscle cells, adipose tissue, and macrophages are co-cultured. When co-cultured, pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression increased, whereas decreased anti-inflammatory cytokine (IL-10 and IL-15) expression decreased in both C2C12 and 3T3-L1 cells. Calcitriol increased reactive oxygen species (ROS) production in the media. While adiponectin gene expression decreased, leptin, resistin, CCAAT-enhancer-binding protein-beta (C/EBP-β), and peroxisome proliferator-activated receptor gamma (PPAR-γ) gene expression was significantly (P cultured with two different cell types. Inducible nitric oxide synthase (iNOS) protein levels were also stimulated in the C2C12 and 3T3-L1 cells, but arginase l was attenuated by calcitriol. Cacitriol highly amplified (P = 0.008) µ-calpain gene expression in co-cultured C2C12 cells. The results showed an overall increase in pro-inflammatory cytokines and a decrease in anti-inflammatory cytokines of C2C12 and 3T3-L1 cells with calcitriol in co-culture systems. µ-Calpain protein was also augmented in differentiated C2C12 cells with calcitriol. These findings suggest that calcitriol can be used as not only fat synthesizer, but meat tenderizer, in meat-producing animals. © 2014 International Federation for Cell Biology.

  9. [The process of heme synthesis in bone marrow mesenchymal stem cells cultured under fibroblast growth factor bFGF and hypoxic conditions].

    Science.gov (United States)

    Poleshko, A G; Lobanok, E S; Mezhevikina, L M; Fesenko, E E; Volotkovskiĭ, I D

    2014-01-01

    It was demonstrated that fibroblast growth factor bFGF influences the process of heme synthesis, the proliferation activity and viability of bone marrow mesenchymal stem cells in culture under hypoxic conditions. The addition of fibroblast growth factor bFGF (7 ng/ml) to the medium under above conditions led to the accumulation of aminolevulinic acid--an early porphyrin and heme precursor, an increase in CD 71 expression--a transferrin receptor, and also a decrease in porphyrin pigments and heme contents--a late precursor and end products of heme synthesis, respectively. It was found that cultivation of the cells under hypoxic conditions and bFGF is an optimum to maintain high viability and proliferation capacity of the mesenchymal stem cells.

  10. Identification of EhTIF-IA: The putative E. histolytica orthologue of the human ribosomal RNA transcription initiation factor-IA.

    Science.gov (United States)

    Srivastava, Ankita; Bhattacharya, Alok; Bhattacharya, Sudha; Jhingan, Gagan Deep

    2016-03-01

    Initiation of rDNA transcription requires the assembly of a specific multi-protein complex at the rDNA promoter containing the RNA Pol I with auxiliary factors. One of these factors is known as Rrn3P in yeast and Transcription Initiation Factor IA (TIF-IA) in mammals. Rrn3p/TIF-IA serves as a bridge between RNA Pol I and the pre-initiation complex at the promoter. It is phosphorylated at multiple sites and is involved in regulation of rDNA transcription in a growth-dependent manner. In the early branching parasitic protist Entamoeba histolytica, the rRNA genes are present exclusively on circular extra chromosomal plasmids. The protein factors involved in regulation of rDNA transcription in E. histolytica are not known. We have identified the E. histolytica equivalent of TIF-1A (EhTIF-IA) by homology search within the database and was further cloned and expressed. Immuno-localization studies showed that EhTIF-IA co-localized partially with fibrillarin in the peripherally localized nucleolus. EhTIF-IA was shown to interact with the RNA Pol I-specific subunit RPA12 both in vivo and in vitro. Mass spectroscopy data identified RNA Pol I-specific subunits and other nucleolar proteins to be the interacting partners of EhTIF-IA. Our study demonstrates for the first time a conserved putative RNA Pol I transcription factor TIF-IA in E. histolytica.

  11. Albumin endocytosis via megalin in astrocytes is caveola- and Dab-1 dependent and is required for the synthesis of the neurotrophic factor oleic acid.

    Science.gov (United States)

    Bento-Abreu, André; Velasco, Ana; Polo-Hernández, Erica; Lillo, Concepción; Kozyraki, Renata; Tabernero, Arantxa; Medina, José M

    2009-10-01

    The synthesis and release of the neurotrophic factor oleic acid requires internalization of albumin into the astrocyte, which is mediated by megalin. In this study, we show that the binding and internalization of albumin involve its interaction with megalin, caveolin-1, caveolin-2 and cavin, but not with clathrin in astrocytes from primary culture. Electron microscopy analyses revealed albumin-gold complexes localized in caveolae, but not in clathrin-coated vesicles. Neither chlorpromazine nor silencing clathrin expression modified albumin uptake. Silencing caveolin-1 strongly reduced the binding and internalization of albumin and the distribution of megalin in the plasma membrane. However, silencing caveolin-2 only decreased albumin internalization, suggesting that caveolin-1 is responsible for megalin recruitment to the caveolae and that caveolin-2 participates in caveolae internalization. In most tissues, the cytosolic adaptor protein disabled (Dab)-2 connects megalin to clathrin, astrocytes lack Dab-2; instead, they express Dab-1, which interacts with caveolin-1 and megalin and is required for albumin internalization. The transcytosis of albumin in astrocytes, including the passage through the endoplasmic reticulum, which is a compulsory step for oleic acid synthesis, was confirmed by electron microscopy analyses. Thus, whereas silencing clathrin did not modify the synthesis and release of oleic acid, the knock-down of caveolin-1, caveolin-2 and Dab-1 strongly reduced the synthesis and release of this neurotrophic factor. In conclusion, caveola-mediated endocytosis of albumin requires megalin and the adaptor protein Dab-1 in cultured astrocytes. Albumin endocytosis may be a key step in brain development because it stimulates the synthesis of oleic acid, which in turn promotes neuronal differentiation.

  12. Tc-MYBPA an Arabidopsis TT2-like transcription factor and functions in the regulation of proanthocyanidin synthesis in Theobroma cacao.

    Science.gov (United States)

    Liu, Yi; Shi, Zi; Maximova, Siela N; Payne, Mark J; Guiltinan, Mark J

    2015-06-25

    The flavan-3-ols catechin and epicatechin, and their polymerized oligomers, the proanthocyanidins (PAs, also called condensed tannins), accumulate to levels of up to 15 % of the total weight of dry seeds of Theobroma cacao L. These compounds have been associated with several health benefits in humans. They also play important roles in pest and disease defense throughout the plant. In Arabidopsis, the R2R3 type MYB transcription factor TT2 regulates the major genes leading to the synthesis of PA. To explore the transcriptional regulation of the PA synthesis pathway in cacao, we isolated and characterized an R2R3 type MYB transcription factor MYBPA from cacao. We examined the spatial and temporal gene expression patterns of the Tc-MYBPA gene and found it to be developmentally expressed in a manner consistent with its involvement in PAs and anthocyanin synthesis. Functional complementation of an Arabidopsis tt2 mutant with Tc-MYBPA suggested that it can functionally substitute the Arabidopsis TT2 gene. Interestingly, in addition to PA accumulation in seeds of the Tc-MYBPA expressing plants, we also observed an obvious increase of anthocyanidin accumulation in hypocotyls. We observed that overexpression of the Tc-MYBPA gene resulted in increased expression of several key genes encoding the major structural enzymes of the PA and anthocyanidin pathway, including DFR (dihydroflavanol reductase), LDOX (leucoanthocyanidin dioxygenase) and BAN (ANR, anthocyanidin reductase). We conclude that the Tc-MYBPA gene that encodes an R2R3 type MYB transcription factor is an Arabidopsis TT2 like transcription factor, and may be involved in the regulation of both anthocyanin and PA synthesis in cacao. This research may provide molecular tools for breeding of cacao varieties with improved disease resistance and enhanced flavonoid profiles for nutritional and pharmaceutical applications.

  13. Factor Analysis with EM Algorithm Never Gives Improper Solutions when Sample Covariance and Initial Parameter Matrices Are Proper

    Science.gov (United States)

    Adachi, Kohei

    2013-01-01

    Rubin and Thayer ("Psychometrika," 47:69-76, 1982) proposed the EM algorithm for exploratory and confirmatory maximum likelihood factor analysis. In this paper, we prove the following fact: the EM algorithm always gives a proper solution with positive unique variances and factor correlations with absolute values that do not exceed one,…

  14. Crystallization and preliminary crystallographic studies of the W2 domain of Drosophila melanogaster eukaryotic translation initiation factor 5C domain-containing protein

    International Nuclear Information System (INIS)

    Zhao, Hui; Wang, Hong; Liu, Huihui; Teng, Maikun; Li, Xu

    2012-01-01

    The crystallization and preliminary crystallographic studies of the carboxy-terminal domain of D. melanogaster eukaryotic translation initiation factor 5C domain-containing protein are reported. The Drosophila melanogaster eukaryotic translation initiation factor 5C domain-containing protein (ECP) is composed of two independently folded domains which belong to the basic leucine-zipper and W2 domain-containing protein (BZW) family. Based on the sequence similarity between the C-terminal W2 domain of ECP and some eukaryotic translation initiation factors (such as eIF2B∊, eIF4γ, eIF5 etc.), ECP has been speculated to participate in the translation initiation process. Structural information on the C-terminal W2 domain of ECP would be helpful in understanding the specific cellular function of this protein. Here, the W2 domain of ECP was expressed and crystallized. Crystals grown by the hanging-drop vapour-diffusion method diffracted to 2.70 Å resolution and belonged to space group I4, with unit-cell parameters a = b = 81.05, c = 57.44 Å. The Matthews coefficient suggested that there was one molecule per asymmetric unit in the crystal

  15. Enterovirus 71 contains a type I IRES element that functions when eukaryotic initiation factor eIF4G is cleaved

    International Nuclear Information System (INIS)

    Thompson, Sunnie R.; Sarnow, Peter

    2003-01-01

    Human enterovirus 71 (EV71) is a member of the Enterovirus genus of the Picornaviridae family. Other members of this family utilize an unusual mechanism of translation initiation whereby ribosomes are recruited internally to the viral RNA by an internal ribosome site (IRES) located in their 5' noncoding regions (5' NCR). Using dicistronic reporter constructs, we demonstrate that the 5' NCRs of the 7423/MS/87 and BrCr strains of EV71 function as an IRES both in extracts and in cultured cells. Preincubation of translation extracts with purified coxsackievirus 2A protease cleaved elF4G, a component of the cap binding complex, resulting in a significant decrease in translation of capped mRNAs. In contrast, the translational efficiency of the EV71 IRES was enhanced under this condition, demonstrating that the EV71 IRES functions similar to other enterovirus IRES elements when components of the cap binding protein complex are cleaved. Finally, insertion of an upstream, out-of-frame start codon in the 5' NCR of the EV71 genome inhibited IRES activity, suggesting that EV71 can be classified as a type I IRES, in which ribosomes first bind upstream of the initiation codon and then scan the mRNA until an appropriate downstream AUG start codon is encountered and protein synthesis commences

  16. General adherence to guideline recommendations on initial diagnosis of bladder cancer in the United States and influencing factors.

    Science.gov (United States)

    Karl, Alexander; Adejoro, Oluwakayode; Saigal, Christopher; Konety, Badrinath

    2014-08-01

    Because international guidelines recommend best practices regarding staging of incident bladder cancer, we determined the adherence to such recommendations in the United States, performing a large retrospective database analysis. Patients with the diagnosis of urothelial cancer were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database between 1992 and 2007. Staging procedures were identified and analyzed. As reference for published recommendations, we used the American Urological Association (AUA), European Association of Urology (EAU), and National Comprehensive Cancer Network (NCCN) guidelines. Based on these sources, recommended initial staging of bladder cancer was analyzed. Of all 56,130 patients, 6148 (10.9%) had a cytologic examination, 29,677 (52.9%) had a standard urinalysis, 2882 (5.1%) underwent intravenous pyelography (IVP), 6950 (12.4%) underwent retrograde pyelography (RPG), and 8145 (14.5%) had computed tomography/magnetic resonance imaging (CT/MRI). There was a significant trend over the years to a higher use of cytologic analysis, standard urinalysis, and CT/MRI. We observed a significant trend toward a lower rate of IVP and a stable use of RPG. The limitation of our study is that claims data are designed for payment processing, not quality measurement. Despite published recommendations on the initial diagnosis of bladder cancer, our data show that less than half of the included patients received all the elements thought to be required for an initial diagnosis of bladder cancer as recommended by guidelines. Greater adherence to recommendations may ensure optimal treatment strategies. Appropriate treatment is critical to patient outcomes, because evidence-based therapeutic management can be practiced only if an accurate assessment of the disease takes place at the time of initial diagnosis. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Serotonin receptor B may lock the gate of PTTH release/synthesis in the Chinese silk moth, Antheraea pernyi; a diapause initiation/maintenance mechanism?

    Directory of Open Access Journals (Sweden)

    Qiushi Wang

    Full Text Available The release of prothoracicotropic hormone, PTTH, or its blockade is the major endocrine switch regulating the developmental channel either to metamorphosis or to pupal diapause in the Chinese silk moth, Antheraea pernyi. We have cloned cDNAs encoding two types of serotonin receptors (5HTRA and B. 5HTRA-, and 5HTRB-like immunohistochemical reactivities (-ir were colocalized with PTTH-ir in two pairs of neurosecretory cells at the dorsolateral region of the protocerebrum (DL. Therefore, the causal involvement of these receptors was suspected in PTTH release/synthesis. The level of mRNA(5HTRB responded to 10 cycles of long-day activation, falling to 40% of the original level before activation, while that of 5HTRA was not affected by long-day activation. Under LD 16:8 and 12:12, the injection of dsRNA(5HTRB resulted in early diapause termination, whereas that of dsRNA(5HTRA did not affect the rate of diapause termination. The injection of dsRNA(5HTRB induced PTTH accumulation, indicating that 5HTRB binding suppresses PTTH synthesis also. This conclusion was supported pharmacologically; the injection of luzindole, a melatonin receptor antagonist, plus 5th inhibited photoperiodic activation under LD 16:8, while that of 5,7-DHT, induced emergence in a dose dependent fashion under LD 12:12. The results suggest that 5HTRB may lock the PTTH release/synthesis, maintaining diapause. This could also work as diapause induction mechanism.

  18. Involvement of H- and N-Ras isoforms in transforming growth factor-β1-induced proliferation and in collagen and fibronectin synthesis

    International Nuclear Information System (INIS)

    Martinez-Salgado, Carlos; Fuentes-Calvo, Isabel; Garcia-Cenador, Begona; Santos, Eugenio; Lopez-Novoa, Jose M.

    2006-01-01

    Transforming growth factor β1 (TGF-β1) has a relevant role in the origin and maintenance of glomerulosclerosis and tubule-interstitial fibrosis. TGF-β and Ras signaling pathways are closely related: TGF-β1 overcomes Ras mitogenic effects and Ras counteracts TGF-β signaling. Tubule-interstitial fibrosis is associated to increases in Ras, Erk, and Akt activation in a renal fibrosis model. We study the role of N- and H-Ras isoforms, and the involvement of the Ras effectors Erk and Akt, in TGF-β1-mediated extracellular matrix (ECM) synthesis and proliferation, using embrionary fibroblasts from double knockout (KO) mice for H- and N-Ras (H-ras -/- /N-ras -/- ) isoforms and from heterozygote mice (H-ras +/- /N-ras +/- ). ECM synthesis is increased in basal conditions in H-ras -/- /N-ras -/- fibroblasts, this increase being higher after stimulation with TGF-β1. TGF-β1-induced fibroblast proliferation is smaller in H-ras -/- /N-ras -/- than in H-ras +/- /N-ras +/- fibroblasts. Erk activation is decreased in H-ras -/- /N-ras -/- fibroblasts; inhibition of Erk activation reduces fibroblast proliferation. Akt activation is higher in double KO fibroblasts than in heterozygotes; inhibition of Akt activation also inhibits ECM synthesis. We suggest that H- and N-Ras isoforms downregulate ECM synthesis, and mediate proliferation, in part through MEK/Erk activation. PI3K-Akt pathway activation may be involved in the increase in ECM synthesis observed in the absence of H- and N-Ras

  19. Reframing governance, security and conflict in the light of HIV/AIDS: a synthesis of findings from the AIDS, Security and Conflict Initiative.

    Science.gov (United States)

    de Waal, Alex

    2010-01-01

    This paper draws upon the findings of the AIDS, Security and Conflict Initiative (ASCI) to reach conclusions about the relationship between HIV/AIDS, security, conflict and governance, in the areas of HIV/AIDS and state fragility, the reciprocal interactions between armed conflicts (including post-conflict transitions) and HIV/AIDS, and the impact of HIV/AIDS on uniformed services and their operational effectiveness. Gender issues cut across all elements of the research agenda. ASCI commissioned 29 research projects across regions, disciplines and communities of practice. Over the last decade, approaches to HIV/AIDS as a security threat have altered dramatically, from the early anticipation that the epidemic posed a threat to the basic functioning of states and security institutions, to a more sanguine assessment that the impacts will be less severe than feared. ASCI finds that governance outcomes have been shaped as much by the perception of HIV/AIDS as a security threat, as the actual impacts of the epidemic. ASCI research found that the current indices of fragility at country level did not demonstrate any significant association with HIV, calling into question the models used for asserting such linkages. However at local government level, appreciable impacts can be seen. Evidence from ASCI and elsewhere indicates that conventional indicators of conflict, including the definition of when it ends, fail to capture the social traumas associated with violent disruption and their implications for HIV. Policy frameworks adopted for political and security reasons translate poorly into social and public health policies. Fears of much-elevated HIV rates among soldiers with disastrous impacts on armies as institutions, have been overstated. In mature epidemics, rates of infection among the military resemble those of the peer groups within the general population. Military HIV/AIDS control policies follow a different and parallel paradigm to national (civilian) policies, in

  20. Insights into the functional characteristics of geminivirus rolling-circle replication initiator protein and its interaction with host factors affecting viral DNA replication.

    Science.gov (United States)

    Rizvi, Irum; Choudhury, Nirupam Roy; Tuteja, Narendra

    2015-02-01

    Geminiviruses are DNA viruses that infect several economically important crops, resulting in a reduction in their overall yield. These plant viruses have circular, single-stranded DNA genomes that replicate mainly by a rolling-circle mechanism. Geminivirus infection results in crosstalk between viral and cellular factors to complete the viral life cycle or counteract the infection as part of defense mechanisms of host plants. The geminiviral replication initiator protein Rep is the only essential viral factor required for replication. It is multifunctional and is known to interact with a number of host factors to modulate the cellular environment or to function as a part of the replication machinery. This review provides a holistic view of the research related to the viral Rep protein and various host factors involved in geminiviral DNA replication. Studies on the promiscuous nature of geminiviral satellite DNAs are also reviewed.

  1. Parathyroid hormone blocks the stimulatory effect of insulin-like growth factor-I on collagen synthesis in cultured 21-day fetal rat calvariae

    International Nuclear Information System (INIS)

    Kream, B.E.; Petersen, D.N.; Raisz, L.G.

    1990-01-01

    We examined the interaction of parathyroid hormone (PTH) and recombinant human insulin-like growth factor I (IGF-I) on collagen synthesis in 21-day fetal rat calvariae as assessed by measuring the incorporation of [ 3 H]proline into collagenase-digestible protein. After 96 hours of culture, 10 nM PTH antagonized the stimulation of collagen synthesis and partially blocked the increase in dry weight produced by 10 nM IGF-I. The effect of PTH to block IGF-I stimulated collagen synthesis was observed in the central bone of calvariae and was mimicked by forskolin and phorbol 12-myristate 13-acetate, but not by 1,25-dihydroxyvitamin D3, transforming growth factor-alpha or dexamethasone. Our data are consistent with the concept that the direct effect of PTH is to inhibit basal CDP labeling and fully oppose IGF-I stimulated CDP labeling. The finding that this effect of PTH is mimicked by forskolin and PMA suggests that this block in IGF-I stimulation of CDP labeling involves both cAMP and protein kinase C mediated pathways

  2. Norovirus translation requires an interaction between the C Terminus of the genome-linked viral protein VPg and eukaryotic translation initiation factor 4G.

    Science.gov (United States)

    Chung, Liliane; Bailey, Dalan; Leen, Eoin N; Emmott, Edward P; Chaudhry, Yasmin; Roberts, Lisa O; Curry, Stephen; Locker, Nicolas; Goodfellow, Ian G

    2014-08-01

    Viruses have evolved a variety of mechanisms to usurp the host cell translation machinery to enable translation of the viral genome in the presence of high levels of cellular mRNAs. Noroviruses, a major cause of gastroenteritis in man, have evolved a mechanism that relies on the interaction of translation initiation factors with the virus-encoded VPg protein covalently linked to the 5' end of the viral RNA. To further characterize this novel mechanism of translation initiation, we have used proteomics to identify the components of the norovirus translation initiation factor complex. This approach revealed that VPg binds directly to the eIF4F complex, with a high affinity interaction occurring between VPg and eIF4G. Mutational analyses indicated that the C-terminal region of VPg is important for the VPg-eIF4G interaction; viruses with mutations that alter or disrupt this interaction are debilitated or non-viable. Our results shed new light on the unusual mechanisms of protein-directed translation initiation. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. ERK 1/2 kinase metabolic pathway is responsible for phosphorylation of translation initiation factor eIF4E during in vitro maturation of pig oocytes

    Czech Academy of Sciences Publication Activity Database

    Ellederová, Zdeňka; Cais, Ondřej; Šušor, Andrej; Uhlířová, Kateřina; Kovářová, Hana; Jelínková, Lucie; Tomek, W.; Kubelka, Michal

    2008-01-01

    Roč. 75, č. 2 (2008), s. 309-317 ISSN 1040-452X R&D Projects: GA ČR GA524/04/0104 Grant - others:Deutsche Forschungsgemeinschaft(DE) 463 TSE 113/28 Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50110509 Keywords : meiosis * translation initiation * eIF4E Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.287, year: 2008

  4. Isolation and expression of human cytokine synthesis inhibitory factor cDNA clones: Homology to Epstein-Barr virus open reading frame BCRFI

    International Nuclear Information System (INIS)

    Vieira, P.; De Waal-Malefyt, R.; Dang, M.N.; Johnson, K.E.; Kastelein, R.; Fiorentino, D.F.; DeVries, J.E.; Roncarolo, M.G.; Mosmann, T.R.; Moore, K.W.

    1991-01-01

    The authors demonstrated the existence of human cytokine synthesis inhibitory factor (DSIF) [interleukin 10 (IL-10)]. cDNA clones encoding human IL-10 (hIL-10) were isolated from a tetanus toxin-specific human T-cell clone. Like mouse IL-10, hIL-10 exhibits strong DNA and amino acid sequence homology to an open reading frame in the Epstein-Barr virus, BDRFL. hIL-10 and the BCRFI product inhibit cytokine synthesis by activated human peripheral blood mononuclear cells and by a mouse Th1 clone. Both hIL-10 and mouse IL-10 sustain the viability of a mouse mast cell line in culture, but BCRFI lacks comparable activity in this way, suggesting that BCRFI may have conserved only a subset of hIL-10 activities

  5. Leading-edge flow criticality as a governing factor in leading-edge vortex initiation in unsteady airfoil flows

    Science.gov (United States)

    Ramesh, Kiran; Granlund, Kenneth; Ol, Michael V.; Gopalarathnam, Ashok; Edwards, Jack R.

    2018-04-01

    A leading-edge suction parameter (LESP) that is derived from potential flow theory as a measure of suction at the airfoil leading edge is used to study initiation of leading-edge vortex (LEV) formation in this article. The LESP hypothesis is presented, which states that LEV formation in unsteady flows for specified airfoil shape and Reynolds number occurs at a critical constant value of LESP, regardless of motion kinematics. This hypothesis is tested and validated against a large set of data from CFD and experimental studies of flows with LEV formation. The hypothesis is seen to hold except in cases with slow-rate kinematics which evince significant trailing-edge separation (which refers here to separation leading to reversed flow on the aft portion of the upper surface), thereby establishing the envelope of validity. The implication is that the critical LESP value for an airfoil-Reynolds number combination may be calibrated using CFD or experiment for just one motion and then employed to predict LEV initiation for any other (fast-rate) motion. It is also shown that the LESP concept may be used in an inverse mode to generate motion kinematics that would either prevent LEV formation or trigger the same as per aerodynamic requirements.

  6. Motivational factors for initiating, implementing, and maintaining physical activity behavior following a rehabilitation program for patients with type 2 diabetes: a longitudinal, qualitative, interview study.

    Science.gov (United States)

    Walker, Karen Christina; Valentiner, Laura Staun; Langberg, Henning

    2018-01-01

    To explore motivational factors for initiating, implementing, and maintaining physical activity following a rehabilitation program for patients with type 2 diabetes mellitus. Semi-structured, individual, qualitative interviews with five informants from the InterWalk trial were conducted at three separate occasions; at initiation of the rehabilitation program, at completion of the 12-week program, and 52 weeks after enrolment. Interviews were audio-recorded, transcribed, and analyzed according to Systematic Text Condensation. The framework of Self-Determination Theory was applied to guide analysis after identification of preliminary themes. Commitment and obligation were emphasized as being motivational in initiating physical activity. Toward the termination of the program, this was challenged by an expressed need for autonomy. Successful behavioral change was characterized by transfer of commitment to a new structure in everyday life, which also honored the request for autonomy. Feeling capable of participating in physical activity was facilitated through knowledge, practical experience, and progress and considered motivational, whereas lack of progress extinguished motivation. Finally, enjoyment of the activity was determining for long-term maintenance of physical activity behavior. Satisfaction of innate psychological needs leads to more autonomous regulation of behavior and, through this study, we investigated determining factors for extrinsically motivated behavior and factors of importance to the internalization process.

  7. Stoichiometry and Change of the mRNA Closed-Loop Factors as Translating Ribosomes Transit from Initiation to Elongation

    Czech Academy of Sciences Publication Activity Database

    Wang, X.; Xi, W.; Toomey, S.; Chiang, Y.-CH.; Hašek, Jiří; Laue, T.M.; Denis, C.L.

    2016-01-01

    Roč. 11, č. 3 (2016), e0150616 E-ISSN 1932-6203 Institutional support: RVO:61388971 Keywords : DEADENYLATION IN-VIVO * SACCHAROMYCES-CEREVISIAE * POLY(A)-BINDING PROTEIN Subject RIV: EE - Microbiology, Virology Impact factor: 2.806, year: 2016

  8. Analyzing EFL Teachers’ Initial Job Motivation and Factors Effecting Their Motivation in Fezalar Educational Institutions in Iraq

    Directory of Open Access Journals (Sweden)

    Selcuk Koran

    2015-02-01

    Full Text Available Teacher motivation is one of the primary variables of students’ high performance. It is experienced that students whose teachers are highly motivated are more engaged in the learning process. Therefore, it’s mostly the teacher who determines the level of success or failure in achieving institution’s goal in the educational process. Thus, teachers are expected to demonstrate a high job motivation performance by administrations. However, some teachers seem naturally enthusiastic about teaching while others need to be stimulated, inspired and challenged. There are several factors that provide teachers with necessary motivation driven by which they can work effectively. These factors can be emotional, financial, physical or academic. This study is an attempt to find out what motivates teachers to enter this profession, since the reasons of entering this job has significant influence on their commitment to the job, investigate factors which are responsible for high or low motivation of language teachers in Fezalar Educational Institutions (FEI, which is a Turkish private institution that operates in Iraq, and ascertain the degree to which intrinsic and extrinsic motivational factors impact teachers in their work situation. Based on the review of the recent researches of motivation, in general, and of language teacher motivation, in particular, and relying on the qualitative and quantitative study of the issue, a detailed analysis of some aspects of foreign language teacher motivation is presented in the article. Keywords: teacher motivation, job satisfaction, foreign language teaching, L2 teacher motivation

  9. Low rate of dermatology outpatient visits in Asian-Americans: an initial survey study for associated patient-related factors

    Science.gov (United States)

    2014-01-01

    Background Asian-Americans represent the fastest growing minority group in the United States, but are under-represented patients in outpatient dermatology clinics. At the same time, skin cancer rates in individuals of Asian descent are increasing, but skin cancer detection appears to be delayed in Asian-Americans compared to white individuals. Some health-care provider related factors for this phenomenon have been reported in the literature, but the patient-related factors are unclear. Methods This exploratory study to identify patient-related factors associated with dermatology visits in Asian-Americans was performed after Institutional Review Board (IRB) approval. An anonymous, online survey utilizing validated items was conducted on adults who self-identified as Asian-American in Northern California. Univariate and multivariate logistic regression for dermatology visits as indicated by responses to the question of “ever having had skin checked by a dermatologist” were performed on survey responses pertaining to demographic information, socioeconomic factors, acculturation, knowledge of melanoma warning signs and SSE belief and practice. Results 89.7% of individuals who opened the online survey completed the items, with 469 surveys included in the analysis. Only 60% reported ever performing a SSE, and only 48% reported ever having a skin examination by a dermatologist. Multivariate models showed that “ever performing SSE” (p dermatology clinic visits in Asian-Americans is important so that this potential gap in dermatologic care can be better addressed through future studies. PMID:25085260

  10. Genistein-mediated inhibition of glycosaminoglycan synthesis, which corrects storage in cells of patients suffering from mucopolysaccharidoses, acts by influencing an epidermal growth factor-dependent pathway

    Directory of Open Access Journals (Sweden)

    Barańska Sylwia

    2009-03-01

    Full Text Available Abstract Background Mucopolysaccharidoses (MPS are inherited metabolic disorders caused by mutations leading to dysfunction of one of enzymes involved in degradation of glycosaminoglycans (GAGs. Due to their impaired degradation, GAGs accumulate in cells of patients, which results in dysfunction of tissues and organs. Substrate reduction therapy is one of potential treatment of these diseases. It was demonstrated previously that genistein (4', 5, 7-trihydroxyisoflavone inhibits synthesis and reduces levels of GAGs in cultures of fibroblasts of MPS patients. Recent pilot clinical study indicated that such a therapy may be effective in MPS III (Sanfilippo syndrome. Methods To learn on details of the molecular mechanism of genistein-mediated inhibition of GAG synthesis, efficiency of this process was studied by measuring of incorporation of labeled sulfate, storage of GAGs in lysosomes was estimated by using electron microscopic techniques, and efficiency of phosphorylation of epidermal growth factor (EGF receptor was determined by using an ELISA-based assay with fluorogenic substrates. Results Effects of genistein on inhibition of GAG synthesis and accumulation in fibroblasts from patients suffering from various MPS types were abolished in the presence of an excess of EGF, and were partially reversed by an increased concentration of genistein. No such effects were observed when an excess of 17β-estradiol was used instead of EGF. Moreover, EGF-mediated stimulation of phsophorylation of the EGF receptor was impaired in the presence of genistein in both wild-type and MPS fibroblasts. Conclusion The results presented in this report indicate that the mechanism of genistein-mediated inhibition of GAG synthesis operates through epidermal growth factor (EGF-dependent pathway.

  11. Effects of High Glucose on Vascular Endothelial Growth Factor Synthesis and Secretion in Aortic Vascular Smooth Muscle Cells from Obese and Lean Zucker Rats

    Directory of Open Access Journals (Sweden)

    Mariella Trovati

    2012-07-01

    Full Text Available Type 1 diabetes is characterized by insulin deficiency, type 2 by both insulin deficiency and insulin resistance: in both conditions, hyperglycaemia is accompanied by an increased cardiovascular risk, due to increased atherosclerotic plaque formation/instabilization and impaired collateral vessel formation. An important factor in these phenomena is the Vascular Endothelial Growth Factor (VEGF, a molecule produced also by Vascular Smooth Muscle Cells (VSMC. We aimed at evaluating the role of high glucose on VEGF-A164 synthesis and secretion in VSMC from lean insulin-sensitive and obese insulin-resistant Zucker rats (LZR and OZR. In cultured aortic VSMC from LZR and OZR incubated for 24 h with D-glucose (5.5, 15 and 25 mM or with the osmotic controls L-glucose and mannitol, we measured VEGF-A164 synthesis (western, blotting and secretion (western blotting and ELISA. We observed that: (i D-glucose dose-dependently increases VEGF-A164 synthesis and secretion in VSMC from LZR and OZR (n = 6, ANOVA p = 0.002–0.0001; (ii all the effects of 15 and 25 mM D-glucose are attenuated in VSMC from OZR vs. LZR (p = 0.0001; (iii L-glucose and mannitol reproduce the VEGF-A164 modulation induced by D-glucose in VSMC from both LZR and OZR. Thus, glucose increases via an osmotic mechanism VEGF synthesis and secretion in VSMC, an effect attenuated in the presence of insulin resistance.

  12. Tumors initiated by constitutive Cdk2 activation exhibit transforming growth factor beta resistance and acquire paracrine mitogenic stimulation during progression

    DEFF Research Database (Denmark)

    Corsino, P.; Davis, B.; Law, M.

    2007-01-01

    ) promoter results in mammary gland hyperplasia and fibrosis, and mammary tumors. Cell lines isolated from MMTV-cyclin D1-Cdk2 (MMTV-D1K2) tumors exhibit Rb and p130 hyperphosphorylation and up-regulation of the protein products of E2F-dependent genes. These results suggest that cyclin D1/Cdk2 complexes may...... mediate some of the transforming effects that result from cyclin D1 overexpression in human breast cancers. MMTV-DIK2 cancer cells express the hepatocyte growth factor (HGF) receptor, c-Met. MMTV-D1K2 cancer cells also secrete transforming growth factor beta (TGF beta), but are relatively resistant to TGF...

  13. Changes in Theory-Based Psychological Factors Predict Weight Loss in Women with Class III Obesity Initiating Supported Exercise

    Directory of Open Access Journals (Sweden)

    James J. Annesi

    2010-01-01

    Full Text Available Background. Psychological factors' effect on weight loss is poorly understood, in general, and specifically in the severely obese. Objective. To examine whether a behavioral model based on tenets of social cognitive and self-efficacy theory will increase understanding of the relationship between exercise and weight loss. Methods. Fifty-one women with severe obesity participated in a 24-week exercise and nutrition information treatment and were measured on changes in psychological factors and exercise attendance. Results. A significant portion of the variance in BMI change (adjusted for number of predictors was accounted for by the behavioral model (2adj=0.23. Entry of exercise session attendance only marginally improved the prediction to 0.27. Only 19% of the weight lost was directly attributable to caloric expenditure from exercise. Conclusions. Findings suggest that participation in an exercise program affects weight loss through psychological pathways and, thus, may be important in the behavioral treatment of severe obesity.

  14. Analysis of psychosocial factors influencing the distribution and projection of Spanish scientific activity: report of the initial qualitative study

    Directory of Open Access Journals (Sweden)

    GESCIT (Grup d'Estudis Socials de la Ciència i la Tecnologia

    2007-11-01

    Full Text Available In this first phase of a longer study, we identify a number of psycho-social factors which are affecting science in Spain: attitudes, stereotypes, prejudices, values, beliefs, and attribution processes. We also examine how these factors might help or hinder Spanish science's greater impact in the international scientific community. This study falls within the framework of the Social Psychology of Science, the main principle of which is to explain scientific work by appeal to psycho-social variables and processes. We use qualitative methods to analyse a wide sample of material gleaned from the Spanish scientific community, and report on those elements that construct and perpetuate the perceptions, images and representations of current Spanish science research.

  15. A new strategy for healthcare-associated pneumonia: a 2-year prospective multicenter cohort study using risk factors for multidrug-resistant pathogens to select initial empiric therapy.

    Science.gov (United States)

    Maruyama, Takaya; Fujisawa, Takao; Okuno, Masataka; Toyoshima, Hirokazu; Tsutsui, Kiyoyuki; Maeda, Hikaru; Yuda, Hisamichi; Yoshida, Masamichi; Kobayashi, Hiroyasu; Taguchi, Osamu; Gabazza, Esteban C; Takei, Yoshiyuki; Miyashita, Naoyuki; Ihara, Toshiaki; Brito, Veronica; Niederman, Michael S

    2013-11-01

    Optimal empiric therapy for hospitalized patients with healthcare-associated pneumonia (HCAP) is uncertain. We prospectively applied a therapeutic algorithm, based on the presence of risk factors for multidrug-resistant (MDR) pathogens in a multicenter cohort study of 445 pneumonia patients, including both community-acquired pneumonia (CAP; n = 124) and HCAP (n = 321). MDR pathogens were more common (15.3% vs 0.8%, P risk factors, one of which was severity of illness (n = 170), vs HCAP patients with 0-1 risk factor (n = 151) had a significantly higher frequency of MDR pathogens (27.1% vs 2%, P risk factor, mortality was lower than with ≥2 MDR risk factors (8.6% vs 18.2%, P = .012). In multivariate analysis, initial treatment failure, but not inappropriate empiric antibiotic therapy, was a mortality risk factor (odds ratio, 72.0). Basing empiric HCAP therapy on its severity and the presence of risk factors for MDR pathogens is a potentially useful approach that achieves good outcomes without excessive use of broad-spectrum antibiotic therapy. Japan Medical Association Center for Clinical Trials, JMA-IIA00054.

  16. The Burden of Provider-Initiated Preterm Birth and Associated Factors: Evidence from the Brazilian Multicenter Study on Preterm Birth (EMIP.

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    Renato T Souza

    Full Text Available About 15 million children are born under 37 weeks of gestation worldwide. Prematurity is the leading cause of neonatal deaths and short/long term morbidities, entailing consequences not only for the individual, but also their family, health agencies, facilities and all community. The provider-initiated preterm birth is currently one of the most important obstetric conditions related to preterm births, particularly in middle and high income countries, thus decreasing the need for therapeutic preterm birth is essential to reduce global prematurity. Therefore detailed knowledge on the factors associated with provider-initiated preterm birth is essential for the efforts to reduce preterm birth rates and its consequences. In this current analysis we aimed to assess the proportion of provider-initiated (pi-PTB among preterm births in Brazil and identify associated factors.This is an analysis of a multicenter cross-sectional study with a nested case-control component called Brazilian Multicenter Study on Preterm Birth (EMIP. EMIP was conducted in 20 referral obstetric hospitals located in the three most populated of the five Brazilian regions. We analysed data of women with pi-PTB, defined as childbirth occurring at less than 37 weeks, medically indicated for maternal/fetal compromise or both; and women with term birth, childbirth at or after 37 weeks. Maternal, sociodemographic, obstetric, prenatal care, delivery, and postnatal characteristics were assessed as possible factors associated with pi-PTB, compared to term births. The overall prevalence of preterm births was 12.3%. Of these, approximately one-third of cases were initiated by the provider. Hypertensive disorders, placental abruption, and diabetes were the main maternal conditions leading to pi-PTB. Caesarean section was the most common mode of delivery. Chronic hypertension (OR 7.47; 95%CI 4.02-13.88, preeclampsia/eclampsia/HELLP syndrome (OR 15.35; 6.57-35.88, multiple pregnancy (OR 12

  17. Alternating Sequence Controlled Copolymer Synthesis of α-Hydroxy Acids via Syndioselective Ring-Opening Polymerization of O-Carboxyanhydrides Using Zirconium/Hafnium Alkoxide Initiators.

    Science.gov (United States)

    Sun, Yangyang; Jia, Zhaowei; Chen, Changjuan; Cong, Yong; Mao, Xiaoyang; Wu, Jincai

    2017-08-09

    The ring-opening polymerization (ROP) of O-carboxyanhydrides (OCAs) can give diverse poly(α-hydroxy acid)s (PAHAs) with different functional groups because of easy modification of the side group of OCAs, which can extend applications of PAHAs widely. The stereoselective polymerization of O-carboxyanhydrides and further sequence controlled alternating copolymerization of OCAs were still big challenges until now for lack of suitable catalysts/initiators. In this work, a highly syndioselective ROP of OCAs system as the first stereoselective example in this area is reported using zirconium/hafnium alkoxides as initiators with the highest P r value up to 0.95. Furthermore, these initiators were successfully applied in the precisely alternating sequence controlled copolymerization of PheOCA and Tyr(Bn)OCA, and alternating copolymerization of LacOCA and PheOCA was also achieved.

  18. Eukaryotic initiation factor 3 (eIF3) and 5’ mRNA leader sequences as agents of translational regulation in Arabidopsis. Final report

    Energy Technology Data Exchange (ETDEWEB)

    von Arnim, Albrecht G. [Univ. of Tennessee, Knoxville, TN (United States)

    2015-02-04

    Protein synthesis, or translation, consumes a sizable fraction of the cell’s energy budget, estimated at 5% and up to 50% in differentiated and growing cells, respectively. Plants also invest significant energy and biomass to construct and maintain the translation apparatus. Translation is regulated by a variety of external stimuli. Compared to transcriptional control, attributes of translational control include reduced sensitivity to stochastic fluctuation, a finer gauge of control, and more rapid responsiveness to environmental stimuli. Yet, our murky understanding of translational control allows few generalizations. Consequently, translational regulation is underutilized in the context of transgene regulation, although synthetic biologists are now beginning to appropriate RNA-level gene regulation into their regulatory circuits. We also know little about how translational control contributes to the diversity of plant form and function. This project explored how an emerging regulatory mRNA sequence element, upstream open reading frames (uORFs), is integrated with the general translation initiation machinery to permit translational regulation on specific mRNAs.

  19. Formation of an 80 S methionyl-tRNA initiation complex with soluble factors from wheat germ.

    Science.gov (United States)

    Giesen, M; Roman, R; Seal, S N; Marcus, A

    1976-10-10

    Wheat germ supernatant is resolved into four fractions, C3alpha, C3beta, D and A, all of which are required in addition to elongation EF1 and EF2 for tobacco mosaic virus-RNA (TMV-RNA)-catalyzed amino acid polymerization. Fractions C3beta and D function in the binding of Met-tRNAiMet to the 40 S ribosomal subunit forming an unstable 40 S-Met-tRNA1Met complex that is detected in sucrose gradients only after fixation with glutaraldehyde. Fraction C3beta binds Met-tRNAiMet suggesting that a C3beta-Met-tRNAiMet complex may be an intermediate in the formation of the 40 S complex. GTP is required for the formation of both the C3beta-Met-tRNAiMet and the 40 S-Met-tRNAiMet complexes. In either reaction the nucleotide is partially replaceable by quanyl-5'-yl methylene diphosphonate (GMP-P (CH2) P) while ATP is inactive. When ATP, C3alpha, mRNA, and magnesium acetate (final concentration 3.6 mM) are added to an incubation reaction containing the 40 S-Met-tRNAiMet complex, a stable 80 S-Met-tRNAiMet complex is formed. Radioactive TM virus-RNA binds specifically to the 80 S-Met-tRNAi complex suggesting that mRNA is a component of this complex. C3beta and D, the fractions required in the formation of the 40 S-Met-tRNAiMet complex, are also required for formation of the 80 S-Met-tRNAiMet complex. In addition, unlabeled Met-trnaiMet does not compete significantly with preformed 40 S-Met-tRNAiMet in the 80 S complex-forming reaction. These observations suggest that the 40 S-Met-tRNAiMet complex is an intermediate in the 80 S reaction. The 80 S-Met-tRNAiMet product of the sequential reaction is reactive with puromycin and on this basis it is tentatively considered to be a functional initiation complex. The additional requirement of Fraction A for amino acid polymerization suggests, however, that the initiation process may be more complex.

  20. Inhibitory effects of bisbenzylisoquinolines on synthesis of the inflammatory cytokines interleukin-1 and tumour necrosis factor-alpha

    Directory of Open Access Journals (Sweden)

    W. Kim Seow

    1993-01-01

    Full Text Available Synthesis of IL-1β and TNFα by human monocytesmacrophages was significantly inhibited by eleven bisbenzylisoquinolines and one half-molecule (benzylisoquinoline, with IC50 values in the μM range. The results indicate that these compounds may have value in the therapy of human diseases where these inflammatory cytokines have a central role in pathogenesis.

  1. L-Arginine is not the limiting factor for nitric oxide synthesis by human alveolar macrophages in vitro

    NARCIS (Netherlands)

    Muijsers, RBR; ten Hacken, NHT; Van Ark, [No Value; Folkerts, G; Nijkamp, FP; Postma, DS

    2001-01-01

    Unlike murine mononuclear phagocytes, human macrophages do not release high amounts of nitric oxide (NO) in vitro despite the presence of nitric oxide synthase (NOS). To determine whether this limited NO synthesis in vitro is due to limited availability of the NOS substrate L-arginine, and putative

  2. Sport and scholastic factors in relation to smoking and smoking initiation in older adolescents: a prospective cohort study in Bosnia and Herzegovina.

    Science.gov (United States)

    Sekulic, Damir; Sisic, Nedim; Terzic, Admir; Jasarevic, Indira; Ostojic, Ljerka; Pojskic, Haris; Zenic, Natasa

    2017-03-22

    Sport and scholastic factors are known to be associated with cigarette smoking in adolescence, but little is known about the causality of this association. The aim of this study was to prospectively explore the relationships of different sport and scholastic factors with smoking prevalence initiation in older adolescents from Bosnia and Herzegovina. In this 2-year prospective cohort study, there were 872 adolescent participants (16 years at baseline; 46% females). The study consisted of baseline tests at the beginning of the third year (September 2013) and follow-up at the end of the fourth year of high school (late May to early June 2015). The independent variables were scholastic and sport-related factors. The dependent variables were (1) smoking at baseline, (2) smoking at follow-up and (3) smoking initiation over the course of the study. Logistic regressions controlling for age, gender and socioeconomic status were applied to define the relationships between independent and dependent variables. School absence at the baseline study was a significant predictor of smoking initiation during the course of the study (OR 1.4, 95% CI 1.1 to 1.8). Those who reported quitting sports at baseline showed an increased risk of smoking at the end of the study (OR 1.4, 95% CI 1.1 to 2.0) and of smoking initiation (OR 1.8, 95% CI 1.3 to 2.0). Adolescents who reported lower competitive achievements in sport were at a higher risk of (1) smoking at baseline (OR 1.5, 95% CI 1.1 to 2.1), (2) smoking at follow-up (OR 1.5, 95% CI 1.1 to 2.1) and (3) smoking initiation (OR 1.6, 95% CI 1.1 to 2.6). In developing accurate antismoking public health policies for older adolescents, the most vulnerable groups should be targeted. The results showed that most participants initiated smoking before 16 years of age. Therefore, further investigations should evaluate the predictors of smoking in younger ages. Published by the BMJ Publishing Group Limited. For permission to use (where not already

  3. Initial estimation of correlation between estrogen receptor status and histopathology, and also some selected prognostic factors in breast cancer patients

    International Nuclear Information System (INIS)

    Cwikla, J.; Badowski, J.; Shafie, D.; Gugala, K.; Koziorowski, M.

    1996-01-01

    The goal of this study was to assess the correlation between estrogen receptor (ER) status and histopathology findings, likewise to assess some selected prognostic factors in patients with breast cancer. The study was carried out on 126 patients with breast cancer. ER concentration was estimated by the standard biochemical assay (DCC-dextran-coated charcoal assay). The correlation between established risk factors like: lymph node status; age menopausal status and ER status were analysed.The ER yielded in 61% positive results. The mean value of ER in invasive ductal carcinoma was 43.9 fmol/mg protein and the mean value of ER in invasive lobular carcinoma 51.4 fmol/mg protein. The significant statistics negative correlation between ER status of pre-menopausal patients with ductal breast carcinoma and regional lymph nodes involvement was found. There was no difference between ER status and histological type of the cancer. No correlation was found between ER status and age of patients. (author)

  4. Tumors initiated by constitutive Cdk2 activation exhibit transforming growth factor beta resistance and acquire paracrine mitogenic stimulation during progression

    DEFF Research Database (Denmark)

    Corsino, P.; Davis, B.; Law, M.

    2007-01-01

    Cyclin D1/cyclin-dependent kinase 2 (Cdk2) complexes are present at high frequency in human breast cancer cell lines, but the significance of this observation is unknown. This report shows that expression of a cyclin D1-Cdk2 fusion protein under the control of the mouse mammary tumor virus (MMITV......) promoter results in mammary gland hyperplasia and fibrosis, and mammary tumors. Cell lines isolated from MMTV-cyclin D1-Cdk2 (MMTV-D1K2) tumors exhibit Rb and p130 hyperphosphorylation and up-regulation of the protein products of E2F-dependent genes. These results suggest that cyclin D1/Cdk2 complexes may...... mediate some of the transforming effects that result from cyclin D1 overexpression in human breast cancers. MMTV-DIK2 cancer cells express the hepatocyte growth factor (HGF) receptor, c-Met. MMTV-D1K2 cancer cells also secrete transforming growth factor beta (TGF beta), but are relatively resistant to TGF...

  5. Factors associated with initiation and completion of the quadrivalent human papillomavirus vaccine series in an ontario cohort of grade 8 girls

    Directory of Open Access Journals (Sweden)

    Kwong Jeffrey C

    2011-08-01

    Full Text Available Abstract Background Although over a hundred million dollars have been invested in offering free quadrivalent human papillomavirus (HPV vaccination to young girls in Ontario, there continues to be very little information about its usage. In order to successfully guide future HPV vaccine programming, it is important to monitor HPV vaccine use and determine factors associated with use in this population. Methods Linking administrative health and immunization databases, we conducted a population-based, retrospective cohort study of girls eligible for Ontario's Grade 8 HPV vaccination program in Kingston, Frontenac, Lennox, and Addington. We determined the proportion of girls who initiated (at least one dose and completed (all three doses the vaccination series overall and according to socio-demographics, vaccination history, health services utilization, medical history, and program year. Multivariable logistic regression was used to estimate the strength of association between individual factors and initiation and completion, adjusted for all other factors. Results We identified a cohort of 2519 girls, 56.6% of whom received at least one dose of the HPV vaccine. Among vaccinated girls, 85.3% received all three doses. Vaccination history was the strongest predictor of initiation in that girls who received the measles-mumps-rubella, meningococcal C, and hepatitis B vaccines were considerably more likely to also receive the HPV vaccine (odds ratio 4.89; 95% confidence interval 4.04-5.92. Nevertheless, HPV vaccine uptake was more than 20% lower than that of these other vaccines. In addition, while series initiation was not influenced by income, series completion was. In particular, girls of low income were the least likely to receive all three indicated doses of the HPV vaccine (odds ratio 0.45; 95% confidence interval 0.28-0.72. Conclusions The current low level of HPV vaccine acceptance in Kingston, Frontenac, Lennox, and Addington will likely have

  6. Prospective Analysis of the Influence of Sport and Educational Factors on the Prevalence and Initiation of Smoking in Older Adolescents from Croatia.

    Science.gov (United States)

    Zenic, Natasa; Ban, Djivo; Jurisic, Sanja; Cubela, Mladen; Rodek, Jelena; Ostojic, Ljerka; Jelicic, Mario; Bianco, Antonino; Sekulic, Damir

    2017-04-20

    The prevalence of smoking among Croatian adolescents is alarmingly high, but no previous study has prospectively examined the sport- and academic-factors associated with smoking and smoking initiation. This study aimed to prospectively examine the associations between scholastic (educational) achievement and sport factors and smoking in 16- to 18-year-old adolescents. This two-year prospective cohort study included 644 adolescents who were 16 years of age at baseline (46% females). Baseline testing was implemented at the beginning of the 3rd year of high school (September 2014) when participants were 16 years old. Follow-up testing was completed at the end of the fourth year of high school, which occurred 20 months later. The evaluated predictor variables were educational-achievement- and sport-related-factors. The outcome variables were (i) smoking at baseline; (ii) smoking at follow-up; and (iii) smoking initiation over the course of the study. We assessed the associations between predictors and outcomes using logistic regression models adjusted for age, gender, socioeconomic status, and conflict with parents. The educational variables were consistently associated with smoking, with lower grade-point-average (Baseline: odd ratio (OR): 2.01, 95% confidence interval (CI): 1.61-2.55; Follow-up: 1.59, 1.31-1.94), more frequent absence from school (Baseline: OR: 1.40, 95% CI: 1.19-1.69; Follow-up: 1.30, 1.08-1.58), and lower behavioral grades (Baseline: OR: 1.80, 95% CI: 1.10-2.89; Follow-up: 1.57, 1.03-2.41) in children who smoke. Adolescents who reported quitting sports were at greater odds of being smokers (Baseline: 2.07, 1.31-3.32; Follow-up: 1.66, 1.09-2.56). Sport competitive achievement at baseline was protective against smoking initiation during following two-year period (0.45, 0.21-0.91). While the influence of the educational variables on smoking initiation has been found to be established earlier; sport achievement was identified as a significant

  7. Prospective Analysis of the Influence of Sport and Educational Factors on the Prevalence and Initiation of Smoking in Older Adolescents from Croatia

    Directory of Open Access Journals (Sweden)

    Natasa Zenic

    2017-04-01

    Full Text Available The prevalence of smoking among Croatian adolescents is alarmingly high, but no previous study has prospectively examined the sport- and academic-factors associated with smoking and smoking initiation. This study aimed to prospectively examine the associations between scholastic (educational achievement and sport factors and smoking in 16- to 18-year-old adolescents. This two-year prospective cohort study included 644 adolescents who were 16 years of age at baseline (46% females. Baseline testing was implemented at the beginning of the 3rd year of high school (September 2014 when participants were 16 years old. Follow-up testing was completed at the end of the fourth year of high school, which occurred 20 months later. The evaluated predictor variables were educational-achievement- and sport-related-factors. The outcome variables were (i smoking at baseline; (ii smoking at follow-up; and (iii smoking initiation over the course of the study. We assessed the associations between predictors and outcomes using logistic regression models adjusted for age, gender, socioeconomic status, and conflict with parents. The educational variables were consistently associated with smoking, with lower grade-point-average (Baseline: odd ratio (OR: 2.01, 95% confidence interval (CI: 1.61–2.55; Follow-up: 1.59, 1.31–1.94, more frequent absence from school (Baseline: OR: 1.40, 95% CI: 1.19–1.69; Follow-up: 1.30, 1.08–1.58, and lower behavioral grades (Baseline: OR: 1.80, 95% CI: 1.10–2.89; Follow-up: 1.57, 1.03–2.41 in children who smoke. Adolescents who reported quitting sports were at greater odds of being smokers (Baseline: 2.07, 1.31–3.32; Follow-up: 1.66, 1.09–2.56. Sport competitive achievement at baseline was protective against smoking initiation during following two-year period (0.45, 0.21–0.91. While the influence of the educational variables on smoking initiation has been found to be established earlier; sport achievement was identified

  8. Crystallization and preliminary crystallographic studies of the W2 domain of Drosophila melanogaster eukaryotic translation initiation factor 5C domain-containing protein.

    Science.gov (United States)

    Zhao, Hui; Wang, Hong; Liu, Huihui; Teng, Maikun; Li, Xu

    2012-11-01

    The Drosophila melanogaster eukaryotic translation initiation factor 5C domain-containing protein (ECP) is composed of two independently folded domains which belong to the basic leucine-zipper and W2 domain-containing protein (BZW) family. Based on the sequence similarity between the C-terminal W2 domain of ECP and some eukaryotic translation initiation factors (such as eIF2Bℇ, eIF4γ, eIF5 etc.), ECP has been speculated to participate in the translation initiation process. Structural information on the C-terminal W2 domain of ECP would be helpful in understanding the specific cellular function of this protein. Here, the W2 domain of ECP was expressed and crystallized. Crystals grown by the hanging-drop vapour-diffusion method diffracted to 2.70 Å resolution and belonged to space group I4, with unit-cell parameters a=b=81.05, c=57.44 Å. The Matthews coefficient suggested that there was one molecule per asymmetric unit in the crystal.

  9. In vitro ischemia suppresses hypoxic induction of hypoxia-inducible factor-1α by inhibition of synthesis and not enhanced degradation.

    Science.gov (United States)

    Karuppagounder, Saravanan S; Basso, Manuela; Sleiman, Sama F; Ma, Thong C; Speer, Rachel E; Smirnova, Natalya A; Gazaryan, Irina G; Ratan, Rajiv R

    2013-08-01

    Hypoxia-inducible factor (HIF) mediates a broad, conserved adaptive response to hypoxia, and the HIF pathway is a potential therapeutic target in cerebral ischemia. This study investigated the mechanism by which in vitro ischemia (oxygen-glucose deprivation; OGD) affects canonical hypoxic HIF-1α stabilization. We validated the use of a reporter containing the oxygen-dependent degradation domain of HIF-1α fused to firefly luciferase (ODD-luc) to monitor quantitatively distinct biochemical events leading to hypoxic HIF-1α expression or stabilization in a human neuroblastoma cell line (SH-SY5Y). When OGD was imposed following a 2-hr hypoxic stabilization of ODD-luc, the levels of the reporter were reduced, consistent with prior models proposing that OGD enhances HIF prolylhydroxylase (PHD) activity. Surprisingly, PHD inhibitors and proteasome inhibitors do not stabilize ODD-luc in OGD. Furthermore, OGD does not affect the half-life of ODD-luc protein following hypoxia, suggesting that OGD abrogates hypoxic HIF-1α induction by reducing HIF-1α synthesis rather than by enhancing its degradation. We observed ATP depletion under OGD vs. hypoxia and propose that ATP depletion enhances translational suppression, overcoming the selective synthesis of HIF concurrent with global decreases in protein synthesis in hypoxia. Taken together, these findings biochemically characterize a practical reporter for monitoring HIF-1α levels and support a novel model for HIF regulation in an in vitro model of human ischemia. Copyright © 2013 Wiley Periodicals, Inc.

  10. Cloning and characterization of pvdS, a gene required for pyoverdine synthesis in Pseudomonas aeruginosa: PvdS is probably an alternative sigma factor.

    Science.gov (United States)

    Cunliffe, H E; Merriman, T R; Lamont, I L

    1995-05-01

    Cells of Pseudomonas aeruginosa secrete a fluorescent yellow-green siderophore, pyoverdine, when grown under iron-deficient conditions. We describe here the cloning and characterization of a gene, pvdS, which is required for this process. The pvdS gene is required for expression from promoters of at least two pyoverdine synthesis genes and can cause expression from these promoters in Escherichia coli, where they are otherwise inactive. Sequencing of pvdS revealed that it is a member of a subfamily of RNA polymerase sigma factors which direct the synthesis of extracellular products by bacteria. The pvdS gene is expressed only in iron-starved bacteria, and in E. coli cells at least, expression is regulated by the Fur repressor protein. We propose that in iron-rich cells of P. aeruginosa, Fur binds to the pvdS promoter and prevents expression of the gene; under conditions of iron starvation, repression is relieved and PvdS is made, reprogramming the cells for pyoverdine synthesis.

  11. Analysis and synthesis of laughter

    Science.gov (United States)

    Sundaram, Shiva; Narayanan, Shrikanth

    2004-10-01

    There is much enthusiasm in the text-to-speech community for synthesis of emotional and natural speech. One idea being proposed is to include emotion dependent paralinguistic cues during synthesis to convey emotions effectively. This requires modeling and synthesis techniques of various cues for different emotions. Motivated by this, a technique to synthesize human laughter is proposed. Laughter is a complex mechanism of expression and has high variability in terms of types and usage in human-human communication. People have their own characteristic way of laughing. Laughter can be seen as a controlled/uncontrolled physiological process of a person resulting from an initial excitation in context. A parametric model based on damped simple harmonic motion to effectively capture these diversities and also maintain the individuals characteristics is developed here. Limited laughter/speech data from actual humans and synthesis ease are the constraints imposed on the accuracy of the model. Analysis techniques are also developed to determine the parameters of the model for a given individual or laughter type. Finally, the effectiveness of the model to capture the individual characteristics and naturalness compared to real human laughter has been analyzed. Through this the factors involved in individual human laughter and their importance can be better understood.

  12. Factors associated with relational coordination between health professionals involved in insulin initiation in the general practice setting for people with type 2 diabetes.

    Science.gov (United States)

    Manski-Nankervis, Jo-Anne; Furler, John; Young, Doris; Patterson, Elizabeth; Blackberry, Irene

    2015-09-01

    To examine associations between characteristics of general practice settings and primary healthcare providers (general practitioners and practice nurses) and the degree of relational coordination for the task of insulin initiation for type 2 diabetes between primary healthcare providers and diabetes specialists. Relational coordination is a component of effective chronic disease management and can be used to measure collaboration and communication between health professionals. High levels of relational coordination may be important to support insulin initiation in general practice. Cross-sectional study. Surveys were completed by general practitioners and practice nurses participating in the Stepping Up trial. Data on demographics, practice characteristics and relational coordination were collected between October 2012-June 2014. Univariate and multivariate analyses examined factors associated with relational coordination. General practitioners (n = 174) and 115 practice nurses from 78 general practices were included in the analysis. General practice characteristics associated with relational coordination were geographical location and number of administrative staff. Female general practitioners and older practice nurses reported lower relational coordination. Practice nurses with diabetes educator qualifications and experience in insulin initiation reported higher relational coordination. An expanded role and experience of practice nurses in diabetes care increased relational coordination and has the potential to deliver more effective chronic disease management in general practice. Practice and health professional characteristics should be taken into account when designing models of care to increase insulin initiation. © 2015 John Wiley & Sons Ltd.

  13. Synthesis of interleukin 6 (interferon-. beta. /sub 2//B cell stimulatory factor 2) in human fibroblasts is triggered by an increase in intracellular cyclic AMP

    Energy Technology Data Exchange (ETDEWEB)

    Zhange, Y.; Lin, J.X.; Vilcek, J.

    1988-05-05

    Interleukin 6 (IL-6; also referred to as interferon-..beta../sub 2/, 26-kDa protein, and B cell stimulatory factor 2) is a cytokine whose actions include a stimulation of immunoglobulin synthesis, enhancement of B cell growth, and modulation of acute phase protein synthesis by hepatocytes. Synthesis of IL-6 is stimulated by interleukin 1 (IL-1), tumor necrosis factor (TNF), or platelet-derived growth factor. The authors examined the role of the cyclic AMP (cAMP)-dependent signal transduction pathway in IL-6 gene expression. Several activators of adenylate cyclase, including prostaglandin E1, forskolin, and cholera toxin, as well as the phosphodiesterase inhibitor isobutylmethylxanthine and the cAMP analog dibutyryl cAMP, shared the ability to cause a dramatic and sustained increase in IL-6 mRNA levels in human FS-4 fibroblasts. Actinomycin D treatment abolished this enhancement. Treatments that increased intracellular cAMP also stimulated the secretion of the IL-6 protein in a biologically active form. Increased intracellular cAMP appears to enhance IL-6 gene expression by a protein kinase C-independent mechanism because down-regulation of protein kinase C by a chronic exposure of cells to a high dose of 12-O-tetradecanoylphorbol 13-acetate did not abolish the enhancement of IL-6 expression by treatments that increase cAMP. IL-1 and TNF too increased IL-6 mRNA levels by a protein kinase C-independent mechanism. The results suggest a role for the cAMP-dependent pathway(s) in IL-6 gene activation by TNF and IL-1.

  14. Synthesis of interleukin 6 (interferon-β2/B cell stimulatory factor 2) in human fibroblasts is triggered by an increase in intracellular cyclic AMP

    International Nuclear Information System (INIS)

    Zhange, Y.; Lin, J.X.; Vilcek, J.

    1988-01-01

    Interleukin 6 (IL-6; also referred to as interferon-β 2 , 26-kDa protein, and B cell stimulatory factor 2) is a cytokine whose actions include a stimulation of immunoglobulin synthesis, enhancement of B cell growth, and modulation of acute phase protein synthesis by hepatocytes. Synthesis of IL-6 is stimulated by interleukin 1 (IL-1), tumor necrosis factor (TNF), or platelet-derived growth factor. The authors examined the role of the cyclic AMP (cAMP)-dependent signal transduction pathway in IL-6 gene expression. Several activators of adenylate cyclase, including prostaglandin E1, forskolin, and cholera toxin, as well as the phosphodiesterase inhibitor isobutylmethylxanthine and the cAMP analog dibutyryl cAMP, shared the ability to cause a dramatic and sustained increase in IL-6 mRNA levels in human FS-4 fibroblasts. Actinomycin D treatment abolished this enhancement. Treatments that increased intracellular cAMP also stimulated the secretion of the IL-6 protein in a biologically active form. Increased intracellular cAMP appears to enhance IL-6 gene expression by a protein kinase C-independent mechanism because down-regulation of protein kinase C by a chronic exposure of cells to a high dose of 12-O-tetradecanoylphorbol 13-acetate did not abolish the enhancement of IL-6 expression by treatments that increase cAMP. IL-1 and TNF too increased IL-6 mRNA levels by a protein kinase C-independent mechanism. The results suggest a role for the cAMP-dependent pathway(s) in IL-6 gene activation by TNF and IL-1

  15. Factors affecting initial training success of blood glucose testing in captive chimpanzees (Pan troglodytes)

    DEFF Research Database (Denmark)

    Reamer, Lisa A; Haller, Rachel L; Thiele, Erica J

    2014-01-01

    Type 2 diabetes can be a problem for captive chimpanzees. Accurate blood glucose (BG) readings are necessary to monitor and treat this disease. Thus, obtaining voluntary samples from primates through positive reinforcement training (PRT) is critical. The current study assessed the voluntary...... participation of 123 chimpanzees in BG sampling and investigated factors that may contribute to individual success. All subjects participate in regular PRT sessions as part of a comprehensive behavioral management program. Basic steps involved in obtaining BG values include: voluntarily presenting a finger...... important implications for captive management and training program success, underlining individual differences in training aptitude and the need for developing individual management plans in order to provide optimal care and treatment for diabetic chimpanzees in captivity....

  16. Using narratives to understand the motivational factors and experience of being a self-initiated academic expatriate in South Africa

    Directory of Open Access Journals (Sweden)

    Tinashe T. Harry

    2017-08-01

    Full Text Available Orientation: A growing movement of foreign nationals is settling in South Africa. Given this, there is a need to understand not only those factors influencing foreign nationals to settle in South Africa but also their lived experiences as a basis for individual career development. Research purpose: To investigate the expatriation motivational factors and experiences of selfinitiated academic expatriates in South Africa. Motivation for the study: Calls have been made within the careers literature for more empirical focus on understanding career development using some of the neglected sample groups. Research approach, design and method: The interpretive paradigm was adopted to understand the main purpose of the study. Guided by study objectives, unstructured interviews were conducted using a sample of foreign academics working in South Africa (n = 25. Main findings: Individual stories and narratives highlighted that academics relocated for the following reasons: (1 individual preference, (2 economic meltdown and (3 political conditions. Furthermore, the lived experiences of the expatriates reflected discrimination within the workplace and the community of residences in South Africa. Practical and managerial implications: Research findings indicate that the human resources (HR function can come up with interventions that positively influence the lived experience and career development of foreign academics working in South Africa. Contribution: The expatriate experience framed in this study provides a picture of the career development processes of neglected sample groups in the extant literature. Such an understanding is key in advancing literature and proposing interventions. All this is important given the global trend on labour and skills movement added to the role South Africa plays in the international arena.

  17. Neurotoxin synthesis is positively regulated by the sporulation transcription factor Spo0A in Clostridium botulinum type E.

    Science.gov (United States)

    Mascher, Gerald; Mertaoja, Anna; Korkeala, Hannu; Lindström, Miia

    2017-10-01

    Clostridium botulinum produces the most potent natural toxin, the botulinum neurotoxin (BoNT), probably to create anaerobiosis and nutrients by killing the host, and forms endospores that facilitate survival in harsh conditions and transmission. Peak BoNT production coincides with initiation of sporulation in C. botulinum cultures, which suggests common regulation. Here, we show that Spo0A, the master regulator of sporulation, positively regulates BoNT production. Insertional inactivation of spo0A in C. botulinum type E strain Beluga resulted in significantly reduced BoNT production and in abolished or highly reduced sporulation in relation to wild-type controls. Complementation with spo0A restored BoNT production and sporulation. Recombinant DNA-binding domain of Spo0A directly bound to a putative Spo0A-binding box (CTTCGAA) within the BoNT/E operon promoter, demonstrating direct regulation. Spo0A is the first neurotoxin regulator reported in C. botulinum type E. Unlike other C. botulinum strains that are terrestrial and employ the alternative sigma factor BotR in directing BoNT expression, C. botulinum type E strains are adapted to aquatic ecosystems, possess distinct epidemiology and lack BotR. Our results provide fundamental new knowledge on the genetic control of BoNT production and demonstrate common regulation of BoNT production and sporulation, providing a key intervention point for control. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  18. Factores asociados al estadio clínico avanzado en el inicio de la terapia antirretroviral Factors associated to late clinical stage at the initiation of antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Eduardo Warley

    2012-10-01

    Full Text Available A fin de evaluar la frecuencia y posibles factores asociados a la presencia de estadio clínico avanzado al inicio de terapia antirretroviral (ECAITA, efectuamos un análisis retrospectivo de datos de dos cohortes prospectivas de pacientes infectados por HIV que iniciaron terapia antirretroviral (sin tratamiento anterior entre 2005 y 2009. Se analizaron las historias clínicas de 264 pacientes, 123 mujeres (46.6% y 141 hombres (53.4%. La mediana de edad fue de 37.7 años. Observamos ECAITA en 132 casos (50%, de los cuales 102 (77.2% se asociaron a diagnóstico tardío de infección por HIV y 30 (22.8% a pacientes con diagnóstico previo no retenidos en el cuidado clínico de la salud. La mediana de células CD4 fue 120/ml y de carga viral 58 038 copias/ml. El recuento de células CD4 era inferior a 200 cel/ml en 174 pacientes (71.3%. Los hombres presentaron ECAITA con mayor frecuencia que las mujeres (59.8% vs. 40.2%, en quienes el diagnóstico se realizó durante el control de un embarazo en el 25.2% de los casos. Consumo elevado de alcohol (p 0.006, ser soltero (p 0.04 y nivel de educación menor al secundario completo (p 0.008 se asociaron a ECAITA en el análisis bivariado. Ser de sexo masculino (p 0.003 fue el único factor asociado tanto en el análisis bivariado como en el multivariado. Nuestros datos refuerzan la necesidad de expandir el testeo para HIV y deberían impulsar a definir acciones programáticas que promuevan el ingreso precoz al cuidado de la infección por HIV.In order to evaluate the frequency of a late clinical stage in HIV infected patients at onset of antiretroviral therapy (LART and to identify possible associated factors, we performed a retrospective analysis of data reported in two prospective cohorts of HIV infected patients who started antiretroviral therapy for the first time between 2005 and 2009. Medical records of 265 patients -123 women (46.6% and 141 men, median age 37.7 years old- were analyzed. LART was

  19. The Depression Initiative. Description of a collaborative care model for depression and of the factors influencing its implementation in the primary care setting in the Netherlands

    Directory of Open Access Journals (Sweden)

    Fransina J. de Jong

    2009-06-01

    Full Text Available Background: In the Depression Initiative, a promising collaborative care model for depression that was developed in the US was adapted for implementation in the Netherlands. Aim: Description of a collaborative care model for major depressive disorder (MDD and of the factors influencing its implementation in the primary care setting in the Netherlands. Data sources: Data collected during the preparation phase of the CC:DIP trial of the Depression Initiative, literature, policy documents, information sheets from professional associations. Results: Factors facilitating the implementation of the collaborative care model are continuous supervision of the care managers by the consultant psychiatrist and the trainers, a supportive web-based tracking system and the new reimbursement system that allows for introduction of a mental health care-practice nurse (MHC-PN in the general practices and coverage of the treatment costs. Impeding factors might be the relatively high percentage of solo-primary care practices, the small percentage of professionals that are located in the same building, unfamiliarity with the concept of collaboration as required for collaborative care, the reimbursement system that demands regular negotiations between each health care provider and the insurance companies and the reluctance general practitioners might feel to expand their responsibility for their depressed patients. Conclusion: Implementation of the collaborative care model in the Netherlands requires extensive training and supervision on micro level, facilitation of reimbursement on meso- and macro level and structural effort to change the treatment culture for chronic mental disorders in the primary care setting.

  20. The Depression Initiative. Description of a collaborative care model for depression and of the factors influencing its implementation in the primary care setting in the Netherlands.

    Science.gov (United States)

    de Jong, Fransina J; van Steenbergen-Weijenburg, Kirsten M; Huijbregts, Klaas M L; Vlasveld, Moniek C; Van Marwijk, Harm W J; Beekman, Aartjan T F; van der Feltz-Cornelis, Christina M

    2009-06-15

    In the Depression Initiative, a promising collaborative care model for depression that was developed in the US was adapted for implementation in the Netherlands. Description of a collaborative care model for major depressive disorder (MDD) and of the factors influencing its implementation in the primary care setting in the Netherlands. Data collected during the preparation phase of the CC:DIP trial of the Depression Initiative, literature, policy documents, information sheets from professional associations. Factors facilitating the implementation of the collaborative care model are continuous supervision of the care managers by the consultant psychiatrist and the trainers, a supportive web-based tracking system and the new reimbursement system that allows for introduction of a mental health care-practice nurse (MHC-PN) in the general practices and coverage of the treatment costs. Impeding factors might be the relatively high percentage of solo-primary care practices, the small percentage of professionals that are located in the same building, unfamiliarity with the concept of collaboration as required for collaborative care, the reimbursement system that demands regular negotiations between each health care provider and the insurance companies and the reluctance general practitioners might feel to expand their responsibility for their depressed patients. Implementation of the collaborative care model in the Netherlands requires extensive training and supervision on micro level, facilitation of reimbursement on meso- and macro level and structural effort to change the treatment culture for chronic mental disorders in the primary care setting.

  1. Poly(2-hydroxyethyl methacrylate) (PHEMA) grafted polyethylene/polypropylene (PE/PP) nonwoven fabric by γ-initiation: Synthesis, characterization and benefits of RAFT mediation

    International Nuclear Information System (INIS)

    Kodama, Yasko; Barsbay, Murat; Güven, Olgun

    2014-01-01

    Polyethylene/polypropylene (PE/PP) nonwoven fabrics were functionalized by γ-initiated RAFT mediated grafting of 2-hydroxyethyl methacrylate (HEMA), and the characterization of the grafted samples was carried out using various techniques. FTIR and XPS analysis showed an increase in the oxygenated content till a certain degree of grafting. The results implied a grafting process following the concept of ‘front mechanism’. The initial grafting occurred on the topmost surface layer, and then moved further into the bulk of the polymer matrix. Reversible addition-fragmentation chain transfer (RAFT) mediated grafting yielded a better controlled grafting when compared to those obtained in conventional grafting. - Highlights: • PHEMA was grafted to PE/PP nonwoven fabric via the RAFT polymerization. • Diffusion-controlled grafting was observed in compliance with ‘front mechanism’. • FTIR, XPS, SEM, TGA and contact angle measurements were used for characterization

  2. D-Dimer Levels and Traditional Risk Factors Are Associated With Incident Hypertension Among HIV-Infected Individuals Initiating Antiretroviral Therapy in Uganda.

    Science.gov (United States)

    Okello, Samson; Asiimwe, Stephen B; Kanyesigye, Michael; Muyindike, Winnie R; Boum, Yap; Mwebesa, Bosco B; Haberer, Jessica E; Huang, Yong; Williams, Kenneth; Burdo, Tricia H; Tracy, Russell P; Bangsberg, David R; Mocello, A Rain; Martin, Jeffrey N; Hunt, Peter W; Siedner, Mark J

    2016-12-01

    We sought to describe blood pressure (BP) changes after antiretroviral therapy (ART) initiation and evaluate the association of markers of inflammation with incident hypertension in a cohort of HIV-infected individuals in Uganda. We used mixed effects linear regression to model changes in systolic BP over time among a cohort of HIV-infected individuals initiating ART in Uganda. After exclusion of participants with preexisting hypertension, we identified participants with normal BP throughout follow-up (controls) and those with elevated BP on ≥3 consecutive visits (cases). Before ART initiation, participants had testing for interleukin 6, kynurenine/tryptophan ratio, lipopolysaccharide, soluble CD14, soluble CD163, and D-dimer and those with viral suppression at 6 months during ART had repeat tests. We fit logistic regression models to estimate associations between biomarkers and risk of incident hypertension. In the entire cohort, systolic BP increased by 9.6 mm Hg/yr (95% CI: 7.3 to 11.8) in the first 6 months of ART, then plateaued. Traditional factors: male gender (adjusted odds ratio (AOR) 2.76, 95% CI: 1.34 to 5.68), age (AOR 1.09, 95% CI: 1.04 to 1.13), overweight (AOR 4.48, 95% CI: 1.83 to 10.97), and a CD4 count <100 cells (AOR 3.08, 95% CI: 1.07 to 8.89) were associated with incident hypertension. After adjusting for these, D-dimer levels at month 6 were inversely associated with incident hypertension (AOR 0.61, 95% CI: 0.37 to 0.99). Although not significant, similar associations were seen with sCD14 and kynurenine/tryptophan ratio. BP increases early after ART initiation in Ugandans. Traditional risk factors, rather than immune activation, were associated with incident hypertension in this population.

  3. Factors shaping initial decision-making to self-test amongst cohabiting couples in urban Blantyre, Malawi.

    Science.gov (United States)

    Kumwenda, Moses; Munthali, Alister; Phiri, Mackwellings; Mwale, Daniel; Gutteberg, Tore; MacPherson, Eleanor; Theobald, Sally; Corbett, Liz; Desmond, Nicola

    2014-07-01

    In sub-Saharan Africa, most new HIV infections occur in stable relationships, making couples testing an important intervention for HIV prevention. We explored factors shaping the decision-making of cohabiting couples who opted to self-test in Blantyre, Malawi. Thirty-four self-tested participants (17 couples) were interviewed. Motivators for HIV self-testing (HIVST) emerged at three main levels. Individual motivations included perceived benefits of access to treatment, and self-checking of serostatus in the hope of having been cured by prolonged treatment or faith-healing. HIVST was considered convenient, confidential, reassuring and an enabling new way to test with one's partner. Partnership motivations included both positive (mutual encouragement) and negative (suspected infidelity) aspects. For women, long-term health and togetherness were important goals that reinforced motivations for couples testing, whereas men often needed persuasion despite finding HIVST more flexible and less onerous than facility-based testing. Internal conflict prompted some partners to use HIVST as a way of disclosing their previously concealed HIV positive serostatus. Thus, the implementation of community-based HIVST should acknowledge and appropriately respond to decision-making processes within couples, which are shaped by gender roles and relationship dynamics.

  4. Translation initiation factor eIF4G mediates in vitro poly(A) tail-dependent translation

    Science.gov (United States)

    Tarun, Salvador Z.; Wells, Sandra E.; Deardorff, Julie A.; Sachs, Alan B.

    1997-01-01

    The yeast translation factor eIF4G associates with both the cap-binding protein eIF4E and the poly(A)-binding protein Pab1p. Here we report that the two yeast eIF4G homologs, Tif4631p and Tif4632p, share a conserved Pab1p-binding site. This site is required for Pab1p and poly(A) tails to stimulate the in vitro translation of uncapped polyadenylylated mRNA, and the region encompassing it is required for the cap and the poly(A) tail to synergistically stimulate translation. This region on Tif4631p becomes essential for cell growth when the eIF4E binding site on Tif4631p is mutated. Pab1p mutations also show synthetic lethal interactions with eIF4E mutations. These data suggest that eIF4G mediates poly(A) tail stimulated translation in vitro, and that Pab1p and the domain encompassing the Pab1p-binding site on eIF4G can compensate for partial loss of eIF4E function in vivo. PMID:9256432

  5. Translation initiation factor eIF4G mediates in vitro poly(A) tail-dependent translation.

    Science.gov (United States)

    Tarun, S Z; Wells, S E; Deardorff, J A; Sachs, A B

    1997-08-19

    The yeast translation factor eIF4G associates with both the cap-binding protein eIF4E and the poly(A)-binding protein Pab1p. Here we report that the two yeast eIF4G homologs, Tif4631p and Tif4632p, share a conserved Pab1p-binding site. This site is required for Pab1p and poly(A) tails to stimulate the in vitro translation of uncapped polyadenylylated mRNA, and the region encompassing it is required for the cap and the poly(A) tail to synergistically stimulate translation. This region on Tif4631p becomes essential for cell growth when the eIF4E binding site on Tif4631p is mutated. Pab1p mutations also show synthetic lethal interactions with eIF4E mutations. These data suggest that eIF4G mediates poly(A) tail stimulated translation in vitro, and that Pab1p and the domain encompassing the Pab1p-binding site on eIF4G can compensate for partial loss of eIF4E function in vivo.

  6. The influence of contextual factors on healthcare quality improvement initiatives: what works, for whom and in what setting? Protocol for a realist review.

    Science.gov (United States)

    Coles, Emma; Wells, Mary; Maxwell, Margaret; Harris, Fiona M; Anderson, Julie; Gray, Nicola M; Milner, Gill; MacGillivray, Stephen

    2017-08-23

    Context shapes the effectiveness of knowledge implementation and influences health improvement. Successful healthcare quality improvement (QI) initiatives frequently fail to transfer to different settings, with local contextual factors often cited as the cause. Understanding and overcoming contextual barriers is therefore crucial to implementing effective improvement; yet context is still poorly understood. There is a paucity of information on the mechanisms underlying how and why QI projects succeed or fail in given settings. A realist review of empirical studies of healthcare QI initiatives will be undertaken to examine the influence and impact of contextual factors on quality improvement in healthcare settings and explore whether QI initiatives can work in all contexts. The review will explore which contextual factors are important, and how, why, when and for whom they are important, within varied settings. The dynamic nature of context and change over time will be explored by examining which aspects of context impact at key points in the improvement trajectory. The review will also consider the influence of context on improvement outcomes (provider- and patient-level), spread and sustainability. The review process will follow five iterative steps: (1) clarify scope, (2) search for evidence, (3) appraise primary studies and extract data, (4) synthesise evidence and draw conclusions and (5) disseminate findings. The reviewers will consult with experts and stakeholders in the early stages to focus the review and develop a programme theory consisting of explanatory 'context-mechanism-outcome' configurations. Searches for primary evidence will be conducted iteratively. Data will be extracted and tested against the programme theory. A review advisory group will oversee the review process. Review findings will follow RAMESES guidelines and will be disseminated via a report, presentations and peer-reviewed publications. The review will update and consolidate evidence

  7. Initial weight and virus dose: two factors affecting the onset of acute coxsackievirus B3 myocarditis in C57BL/6 mouse--a histopathology-based study.

    Science.gov (United States)

    Li, Minghui; Wang, Xinggang; Xie, Yuquan; Xie, Yeqing; Zhang, Xian; Zou, Yunzeng; Ge, Junbo; Chen, Ruizhen

    2013-01-01

    C57BL/6 mice have been considered resistant to cardiotropic coxsackievirus B3 (CVB3)-induced myocarditis. However, establishment of viral myocarditis model in C57BL/6 mouse is still a necessity. Here, we discuss the effects of mouse initial body weight and different virus inoculation doses on the onset of acute viral myocarditis in C57BL/6 mouse. According to initial body weight, mice were grouped into group A (3-4 weeks, 11-15 g) and group B (5-6 weeks, 18-20 g). Then, each group was divided into three subgroups inoculated with different virus doses: 1000 50% tissue culture infectious dose (TCID(50))/ml, 10,000 TCID(50)/ml, and 100,000 TCID(50)/ml. Virus existence and myocardium inflammatory infiltration conditions were observed and evaluated 7 days postinfection. Immunohistochemistry staining showed that virus capsid protein VP1 appeared in the myocardia of virus-infected mice. Three subgroups in the lower-body-weight group (group A) came out with a higher mortality (40%-100%), while the higher-body-weight group (group B) showed a tendency for body weight decline. Histopathologically, myocardia of the survival cases in the lower-initial-body-weight group got inflammatory infiltration, while almost no inflammation appeared in the dead cases. In the higher-body-weight group, myocardium inflammatory infiltration deteriorated with the increase of virus doses and bared a relatively sound survival rate. This study indicated that the initial body weight and virus infection dose are two factors affecting the onset of viral myocarditis in C57BL/6 mice. Accordingly, initial body weight of 18-20 g and an inoculation dose of 100,000 TCID(50)/ml × 0.3 ml CVB3 might be an optimal choice to induce acute viral myocarditis in C57BL/6 mice. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Eukaryotic translation initiation factor 5A inhibition alters physiopathology and immune responses in a “humanized” transgenic mouse model of type 1 diabetes

    OpenAIRE

    Imam, Shahnawaz; Mirmira, Raghavendra G.; Jaume, Juan C.

    2014-01-01

    Therapeutic options for treatment of type 1 diabetes (T1D) are still missing. New avenues for immune modulation need to be developed. Here we attempted at altering the diabetes outcome of our humanized model of T1D by inhibiting translation-initiation factor eIF5A hypusination in vivo. Double-transgenic (DQ8-GAD65) mice were immunized with adenoviral vectors carrying GAD65 for diabetes induction. Animals were subsequently treated with deoxyhypusine synthase (DHS) inhibitor GC7 and monitored f...

  9. Factors associated with attrition, mortality, and loss to follow up after antiretroviral therapy initiation: data from an HIV cohort study in India

    Directory of Open Access Journals (Sweden)

    Gerardo Alvarez-Uria

    2013-09-01

    Full Text Available Background: Studies from sub-Saharan Africa have shown high incidence of attrition due to mortality or loss to follow-up (LTFU after initiating antiretroviral therapy (ART. India is the third largest country in the world in terms of HIV infected people, but predictors of attrition after ART initiation are not well known. Design: We describe factors associated with attrition, mortality, and LTFU in 3,159 HIV infected patients who initiated ART between 1 January 2007 and 4 November 2011 in an HIV cohort study in India. The study included 6,852 person-years with a mean follow-up of 2.17 years. Results: After 5 years of follow-up, the estimated cumulative incidence of attrition was 37.7%. There was no significant difference between attrition due to mortality and attrition due to LTFU. Having CD4 counts <100 cells/µl and being homeless [adjusted hazard ratio (aHR 3.1, 95% confidence interval (CI 2.6–3.8] were associated with a higher risk of attrition, and female gender (aHR 0.64, 95% CI 0.6–0.8 was associated with a reduced risk of attrition. Living near a town (aHR 0.82, 95% CI 0.7–0.999 was associated with a reduced risk of mortality. Being single (aHR 1.6, 95% CI 1.2–2.3, illiteracy (aHR 1.3, 95% CI 1.1–1.6, and age <25 years (aHR 1.3, 95% CI 1–1.8 were associated with an increased risk of LTFU. Although the cumulative incidence of attrition in patients diagnosed with tuberculosis after ART initiation was 47.4%, patients who started anti-tuberculous treatment before ART had similar attrition to patients without tuberculosis (36 vs. 35.2%, P=0.19 after four years of follow-up. Conclusions: In this cohort study, the attrition was similar to the one found in sub-Saharan Africa. Earlier initiation of ART, improving the diagnosis of tuberculosis before initiating ART, and giving more support to those patients at higher risk of attrition could potentially reduce the mortality and LTFU after ART initiation.

  10. Factores predictores del inicio y consolidación del consumo de tabaco en adolescentes Analysis of factors related to smoking initiation and continued smoking in young adolescents

    Directory of Open Access Journals (Sweden)

    Araceli Caballero-Hidalgo

    2005-12-01

    Full Text Available Objetivo: Analizar los factores que determinan la adquisición y posterior consolidación del consumo de tabaco en los jóvenes adolescentes. Material y método: Estudio longitudinal de 3 años de duración (2000-2002 sobre jóvenes estudiantes de enseñanza obligatoria, con una edad al inicio del estudio de 13-14 años. Los datos fueron recogidos mediante encuesta individual, cuyo ámbito de estudio era la isla de Gran Canaria, con una muestra final de 745 individuos. Se estimaron modelos de elección binaria condicional de efectos fijos para datos longitudinales, para determinar la probabilidad de probar por primera vez el tabaco («modelo de inicio», así como sobre la probabilidad de ser fumador ocasional o habitual («modelo de experimentación». Resultados: En el último año, el 57% de los adolescentes encuestados ha tenido contacto con el tabaco alguna vez, un 25% más que en el primer año, algunos de ellos (el 9% de forma diaria. En el «modelo de inicio» los determinantes del consumo de tabaco son el interés por el colegio (odds ratio [OR] = 0,27; intervalo de confianza [IC] del 95%, 0,08-0,87, y OR = 0,14; IC del 95%, 0,03-0,58 para los que manifestaron bastante y mucho interés por el colegio, respectivamente, el consumo de tabaco por parte del mejor amigo (OR = 7,44; IC del 95%, 2,59-21,4, el consumo de alcohol (OR = 11,82; IC del 95%, 4,96-28,2, y OR = 15,42; IC del 95%, 4,68-50,7 para los que beben alcohol de manera ocasional o frecuente, respectivamente, y el dinero disponible (euros semanales (OR = 1,13; IC del 95%, 1,07-1,19. Para el «modelo de experimentación», el consumo de tabaco por parte del mejor amigo (OR = 7,01; IC del 95%, 2,96-16,5, el consumo de alcohol (OR = 5,71; IC del 95%, 1,98-16,4, y OR = 5,22; IC del 95%, 1,56-17,5 para los que beben alcohol de manera ocasional o frecuente, respectivamente y los años que lleva como fumador (OR = 1,44; IC del 95%, 1,11-1,86. Conclusiones: El estudio destaca

  11. Factors associated with β-blocker initiation and discontinuation in a population-based cohort of seniors newly diagnosed with heart failure

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    Girouard C

    2016-09-01

    Full Text Available Catherine Girouard,1–3 Jean-Pierre Grégoire,1–3 Paul Poirier,2,4 Jocelyne Moisan1–3 1Chair on Adherence to Treatments, Université Laval, 2Faculty of Pharmacy, Université Laval, 3Population Health and Optimal Health Practices Research Unit, CHU de Québec Research Center, 4Quebec Heart and Lung Institute-Université Laval, Quebec City, QC, Canada Purpose: β-Blockers (bisoprolol, carvedilol, and metoprolol are the cornerstone of heart failure (HF management. The incidence rate of β-blocker initiation and discontinuation and their associated factors among seniors with a first HF diagnosis were assessed.Methods: A population-based inception cohort study that included all individuals aged ≥65 years with a first HF diagnosis in Quebec was conducted. β-Blockers initiation among 91,131 patients who were not using β-blockers at the time of HF diagnosis and discontinuation among those who initiated a β-blocker after HF diagnosis were assessed. Stepwise Cox regression analyses were used to calculate hazard ratios (HR and to identify factors associated with β-blocker initiation and discontinuation.Results: After HF diagnosis, 32,989 (36.2% individuals initiated a β-blocker. Of these, 15,408 (46.7% discontinued their β-blocker during the follow-up. Individuals more likely to initiate a β-blocker were those diagnosed in a recent calendar year (2009: HR, 2.11; 95% confidence interval [CI], 2.00–2.23 and diagnosed by a cardiologist (HR, 1.38; 95% CI, 1.34–1.42. Individuals less likely to initiate were those aged ≥90 years (HR, 0.65; 95% CI, 0.61–0.68 and those with chronic obstructive pulmonary disease (HR, 0.66; 95% CI, 0.64–0.68. Individuals more likely to discontinue were those with more than nine medical consultations (HR, 1.14; 95% CI, 1.10–1.18 and those with dementia (HR, 1.13; 95% CI, 1.01–1.27. Individuals less likely to discontinue were those diagnosed in a recent calendar year (2009: HR 0.74; 95% CI, 0.65–0.82 and

  12. Amphiphilic star block copolymers as gene carrier Part I: Synthesis via ATRP using calix[4]resorcinarene-based initiators and characterization

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Anna; Xue, Yan; Wei, Dafu [Shanghai Key Laboratory of Advanced Polymeric Materials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Guan, Yong, E-mail: yguan@ecust.edu.cn [Shanghai Key Laboratory of Advanced Polymeric Materials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Xiao, Huining [Department of Chemical Engineering, University of New Brunswick, Fredericton, New Brunswick, Canada E3B 5A3 (Canada)

    2013-01-01

    In this work, a cationic star polymer [poly(2-dimethylamino)ethyl methacrylate (PDMAEMA)] was prepared via atom transfer radical polymerization (ATRP), using brominated calix[4]resorcinarene as an initiator. Hydrophobic moieties, methyl methacrylate (MMA) and butyl acrylate (BA), were further incorporated via 'one-pot' method. Well-defined eight-armed star block copolymers bearing hydrophilic blocks inside and hydrophobic blocks outside were synthesized. The molecular weight, particle size, electrophoretic mobility and apparent charge density were determined by gel permeation chromatography (GPC), dynamic light scattering (DLS), phase analysis light scattering (PALS) and colloidal titration, respectively. The zeta potentials and apparent charge densities of the products exhibited the characteristics of polyelectrolyte. The incorporation of hydrophobic moieties generated electrostatic screening effect. The as-synthesized amphiphilic star copolymer is promising as a thermo-sensitive gene carrier for gene therapy. Highlights: Black-Right-Pointing-Pointer Amphiphilic cationic star block copolymers with well-controlled structures were prepared via ATRP. Black-Right-Pointing-Pointer The molecular structures and properties of the initiator and copolymers were systematically characterized. Black-Right-Pointing-Pointer The products exhibited the positive charged character, and hydrophobic moieties generated electrostatic screening effect.

  13. Anionic polymerization of acrylates. Synthesis of (meth)acrylate di- and triblock copolymers using the Li ester-enolate/tert-alkoxide initiating system

    Czech Academy of Sciences Publication Activity Database

    Vlček, Petr; Otoupalová, Jaroslava; Janata, Miroslav; Látalová, Petra; Kurková, Dana; Toman, Luděk; Masař, Bohumil

    2004-01-01

    Roč. 37, č. 2 (2004), s. 344-351 ISSN 0024-9297 R&D Projects: GA ČR GA203/01/0513; GA AV ČR KSK4050111 Institutional research plan: CEZ:AV0Z4050913 Keywords : ligated anionic polymerization * block copolymers Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.898, year: 2004

  14. Low transformation growth factor-β1 production and collagen synthesis correlate with the lack of hepatic periportal fibrosis development in undernourished mice infected with Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    Andreia Ferreira Barros

    2014-04-01

    Full Text Available Undernourished mice infected (UI submitted to low and long-lasting infections by Schistosoma mansoni are unable to develop the hepatic periportal fibrosis that is equivalent to Symmers’ fibrosis in humans. In this report, the effects of the host’s nutritional status on parasite (worm load, egg viability and maturation and host (growth curves, biology, collagen synthesis and characteristics of the immunological response were studied and these are considered as interdependent factors influencing the amount and distribution of fibrous tissue in hepatic periovular granulomas and portal spaces. The nutritional status of the host influenced the low body weight and low parasite burden detected in UI mice as well as the number, viability and maturation of released eggs. The reduced oviposition and increased number of degenerated or dead eggs were associated with low protein synthesis detected in deficient hosts, which likely induced the observed decrease in transformation growth factor (TGF-β1 and liver collagen. Despite the reduced number of mature eggs in UI mice, the activation of TGF-β1 and hepatic stellate cells occurred regardless of the unviability of most miracidia, due to stimulation by fibrogenic proteins and eggshell glycoproteins. However, changes in the repair mechanisms influenced by the nutritional status in deficient animals may account for the decreased liver collagen detected in the present study.

  15. Knockdown of eukaryotic translation initiation factor 3 subunit D (eIF3D) inhibits proliferation of acute myeloid leukemia cells.

    Science.gov (United States)

    Liu, Guo-Zhen; Liu, Ji-Zhu; Li, Xiao-Qing; Zhang, Li; Li, Shuang-Jing; Xiao, Tai-Wu; Wang, Jing-Xia; Li, Guang-Yao; Liu, Yusen

    2018-01-01

    Various eukaryotic translation initiation factors (eIFs) have been implicated in carcinoma development. Eukaryotic translation initiation factor 3 subunit D (eIF3D) has recently been shown to regulate the growth of several types of human cancer cells. However, the function of eIF3D in acute myeloid leukemia (AML) remains unclear. In this study, we investigated the expression of eIF3D in three AML cell lines and a lymphoblast cell line, and found that eIF3D was expressed in all four leukemia cell lines. To explore the role of eIF3D in AML cell proliferation, lentivirus-mediated RNA interference was applied to knock down the expression of eIF3D in U937 cells. The expression of eIF3D was significantly downregulated in U937 cells after eIF3D knockdown, as confirmed by quantitative real-time PCR (qRT-PCR) and Western blot analysis. Knockdown of eIF3D significantly inhibited proliferation of U937 cells. Furthermore, flow cytometry analysis revealed that eIF3D silencing induced cell cycle arrest at the G2/M phase, ultimately leading to apoptosis. Our results indicate that eIF3D plays a key role in the proliferation of AML cells, and suggest that eIF3D silencing might be a potential therapeutic strategy for leukemia.

  16. A systematic review of individual and contextual factors affecting ART initiation, adherence, and retention for HIV-infected pregnant and postpartum women.

    Directory of Open Access Journals (Sweden)

    Ian Hodgson

    Full Text Available Despite progress reducing maternal mortality, HIV-related maternal deaths remain high, accounting, for example, for up to 24 percent of all pregnancy-related deaths in sub-Saharan Africa. Antiretroviral therapy (ART is effective in improving outcomes among HIV-infected pregnant and postpartum women, yet rates of initiation, adherence, and retention remain low. This systematic literature review synthesized evidence about individual and contextual factors affecting ART use among HIV-infected pregnant and postpartum women.Searches were conducted for studies addressing the population (HIV-infected pregnant and postpartum women, intervention (ART, and outcomes of interest (initiation, adherence, and retention. Quantitative and qualitative studies published in English since January 2008 were included. Individual and contextual enablers and barriers to ART use were extracted and organized thematically within a framework of individual, interpersonal, community, and structural categories.Thirty-four studies were included in the review. Individual-level factors included both those within and outside a woman's awareness and control (e.g., commitment to child's health or age. Individual-level barriers included poor understanding of HIV, ART, and prevention of mother-to-child transmission, and difficulty managing practical demands of ART. At an interpersonal level, disclosure to a spouse and spousal involvement in treatment were associated with improved initiation, adherence, and retention. Fear of negative consequences was a barrier to disclosure. At a community level, stigma was a major barrier. Key structural barriers and enablers were related to health system use and engagement, including access to services and health worker attitudes.To be successful, programs seeking to expand access to and continued use of ART by integrating maternal health and HIV services must identify and address the relevant barriers and enablers in their own context that are

  17. Breastfeeding Progression in Preterm Infants Is Influenced by Factors in Infants, Mothers and Clinical Practice: The Results of a National Cohort Study with High Breastfeeding Initiation Rates

    Science.gov (United States)

    Maastrup, Ragnhild; Hansen, Bo Moelholm; Kronborg, Hanne; Bojesen, Susanne Norby; Hallum, Karin; Frandsen, Annemi; Kyhnaeb, Anne; Svarer, Inge; Hallström, Inger

    2014-01-01

    Background and Aim Many preterm infants are not capable of exclusive breastfeeding from birth. To guide mothers in breastfeeding, it is important to know when preterm infants can initiate breastfeeding and progress. The aim was to analyse postmenstrual age (PMA) at breastfeeding milestones in different preterm gestational age (GA) groups, to describe rates of breastfeeding duration at pre-defined times, as well as analyse factors associated with PMA at the establishment of exclusive breastfeeding. Methods The study was part of a prospective survey of a national Danish cohort of preterm infants based on questionnaires and structured telephone interviews, including 1,221 mothers and their 1,488 preterm infants with GA of 24–36 weeks. Results Of the preterm infants, 99% initiated breastfeeding and 68% were discharged exclusively breastfed. Breastfeeding milestones were generally reached at different PMAs for different GA groups, but preterm infants were able to initiate breastfeeding at early times, with some delay in infants less than GA 32 weeks. Very preterm infants had lowest mean PMA (35.5 weeks) at first complete breastfeed, and moderate preterm infants had lowest mean PMA at the establishment of exclusive breastfeeding (36.4 weeks). Admitting mothers to the NICU together with the infant and minimising the use of a pacifier during breastfeeding transition were associated with 1.6 (95% CI 0.4–2.8) and 1.2 days (95% CI 0.1–2.3) earlier establishment of exclusive breastfeeding respectively. Infants that were small for gestational age were associated with 5.6 days (95% CI 4.1–7.0) later establishment of exclusive breastfeeding. Conclusion Breastfeeding competence is not developed at a fixed PMA, but is influenced by multiple factors in infants, mothers and clinical practice. Admitting mothers together with their infants to the NICU and minimising the use of pacifiers may contribute to earlier establishment of exclusive breastfeeding. PMID:25251690

  18. A Systematic Review of Individual and Contextual Factors Affecting ART Initiation, Adherence, and Retention for HIV-Infected Pregnant and Postpartum Women

    Science.gov (United States)

    Hodgson, Ian; Plummer, Mary L.; Konopka, Sarah N.; Colvin, Christopher J.; Jonas, Edna; Albertini, Jennifer; Amzel, Anouk; Fogg, Karen P.

    2014-01-01

    Background Despite progress reducing maternal mortality, HIV-related maternal deaths remain high, accounting, for example, for up to 24 percent of all pregnancy-related deaths in sub-Saharan Africa. Antiretroviral therapy (ART) is effective in improving outcomes among HIV-infected pregnant and postpartum women, yet rates of initiation, adherence, and retention remain low. This systematic literature review synthesized evidence about individual and contextual factors affecting ART use among HIV-infected pregnant and postpartum women. Methods Searches were conducted for studies addressing the population (HIV-infected pregnant and postpartum women), intervention (ART), and outcomes of interest (initiation, adherence, and retention). Quantitative and qualitative studies published in English since January 2008 were included. Individual and contextual enablers and barriers to ART use were extracted and organized thematically within a framework of individual, interpersonal, community, and structural categories. Results Thirty-four studies were included in the review. Individual-level factors included both those within and outside a woman’s awareness and control (e.g., commitment to child’s health or age). Individual-level barriers included poor understanding of HIV, ART, and prevention of mother-to-child transmission, and difficulty managing practical demands of ART. At an interpersonal level, disclosure to a spouse and spousal involvement in treatment were associated with improved initiation, adherence, and retention. Fear of negative consequences was a barrier to disclosure. At a community level, stigma was a major barrier. Key structural barriers and enablers were related to health system use and engagement, including access to services and health worker attitudes. Conclusions To be successful, programs seeking to expand access to and continued use of ART by integrating maternal health and HIV services must identify and address the relevant barriers and enablers in

  19. Geochronological synthesis of Bahia state and the crustal evolution, based in evolution diagram of Sr and initial rate of Sr87/Sr86

    International Nuclear Information System (INIS)

    Sato, K.

    1986-01-01

    The crustal evolution of the ancient terrains of the State of Bahia, Brazil, is attempted with the aid of Sr isotopic results as natural tracers. Some Nd and Pb isotopic data are also available, and support the main conclusions based on Sr evolution diagrams. The analysis of the Sr evolution diagrams shows that the Archean Terrains are mainly formed by accretion from mantle-derived material, but crustal reworking is indicated by the high initial 87 Sr/ 86 Sr value of the Jequie Complex. The Transamazonian mobile belt include both types of materials, but the 87 Sr/ 86 Sr value, generally lower than those of the Jequie Complex, markes improbable a direct derivation. During Middle and Late Proterozoic, the continental crust was already well consolidated, and reworking of crustal material predominated within the Espinhaco and Brasiliano folded systems [pt

  20. Initial treatment seeking from professional health care providers for eating disorders: A review and synthesis of potential barriers to and facilitators of "first contact".

    Science.gov (United States)

    Regan, Pamela; Cachelin, Fary M; Minnick, Alyssa M

    2017-03-01

    The objective of this study is to provide a comprehensive review of empirical research exploring barriers to and facilitators of initial treatment seeking ("first contact") from professional health care providers by adults and young adults with eating disorders (EDs). A search of databases PsycINFO and MEDLINE using the terms "treatment" and "eating disorder*" yielded 9,468 peer-reviewed articles published from January 1945 to June 2016. Screening identified 31 articles meeting the following criteria: (1) participants were 16 or older and presented with a self-reported or clinically diagnosed ED; (2) studies focused on (a) initial treatment seeking (b) for an ED (c) from professional health care providers; (3) articles were empirical, and (4) peer reviewed. Quantitative studies revealed few consistent correlates of treatment seeking, perhaps because most variables were examined in only one or two investigations. Variables with some degree of predictive utility (i.e., produced significant results in multiple studies) were age (older), ethnicity (nonethnic minority), ED type (anorexia, purging BN), specific ED-related behaviors (i.e., purging), and time spent on a treatment waitlist following referral (less). Although BMI was one of the most investigated variables, it did not predict treatment seeking. Qualitative studies revealed the following perceived barriers: (1) personal feelings of shame/fear, (2) ED-related beliefs/perceptions, (3) lack of access/availability, and (4) aspects of the treatment process. Perceived facilitators included (1) health-related concerns, (2) emotional distress, and (3) social support. Implications for clinical practice and areas for further research are discussed. Results highlight the need for shared definitions and methodologies across studies of treatment seeking. © 2017 Wiley Periodicals, Inc.

  1. Synthesis of an Endogenous Steroidal Na Pump Inhibitor Marinobufagenin, Implicated in Human Cardiovascular Diseases, Is Initiated by CYP27A1 via Bile Acid Pathway.

    Science.gov (United States)

    Fedorova, Olga V; Zernetkina, Valentina I; Shilova, Victoria Y; Grigorova, Yulia N; Juhasz, Ondrej; Wei, Wen; Marshall, Courtney A; Lakatta, Edward G; Bagrov, Alexei Y

    2015-10-01

    The bioactive steroid, marinobufagenin, is an endogenous Na/K-ATPase bufadienolide inhibitor that is synthesized by adrenocortical and placental cells. Marinobufagenin binding to Na/K-ATPase initiates profibrotic cell signaling, and heightened marinobufagenin levels are implicated in the pathogenesis of hypertension, preeclampsia, and chronic kidney disease. Steroids are derived from cholesterol through the traditional steroidogenesis pathway initiated by enzyme CYP11A1, and via the acidic bile acid pathway, which is controlled by enzyme CYP27A1. The mechanism of marinobufagenin biosynthesis in mammals, however, remains unknown. Here, we show that post-transcriptional silencing of the CYP27A1 gene in human trophoblast and rat adrenocortical cells reduced the expression of CYP27A1 mRNA by 70%, reduced total bile acids 2-fold, and marinobufagenin levels by 67% when compared with nontreated cells or cells transfected with nontargeting siRNA. In contrast, silencing of the CYP11A1 gene did not affect marinobufagenin production in either cell culture, but suppressed production of progesterone 2-fold in human trophoblast cells and of corticosterone by 90% in rat adrenocortical cells when compared with cells transfected with nontargeting siRNA. In vivo, in a high-salt administration experiment, male and female Dahl salt-sensitive rats became hypertensive after 4 weeks on a high-NaCl diet, their plasma marinobufagenin levels doubled, and adrenocortical CYP27A1 mRNA and protein increased 1.6-fold and 2.0-fold. Therefore, the endogenous steroidal Na/K-ATPase inhibitor, marinobufagenin, is synthesized in mammalian placenta and adrenal cortex from cholesterol through the novel acidic bile acid pathway. These findings will help to understand the role of marinobufagenin in highly prevalent human cardiovascular diseases. © 2015 American Heart Association, Inc.

  2. Self-reported osteoarthritis, ethnicity, body mass index, and other associated risk factors in postmenopausal women-results from the Women's Health Initiative.

    Science.gov (United States)

    Wright, Nicole C; Riggs, Gail Kershner; Lisse, Jeffrey R; Chen, Zhao

    2008-09-01

    The objective of this analysis was to assess risk factors for self-reported osteoarthritis (OA) in an ethnically diverse cohort of women. The participants were postmenopausal women aged 50 to 79 (n=146,494) participating in the clinical trial and observational study of the Women's Health Initiative (WHI). Baseline OA and risk factors were collected from WHI questionnaires. Logistic regression was used to find the association between the risk factors and OA. Risk factor distribution and ethnicity interaction terms were used to assess ethnic differences in OA risk. Forty-four percent of the participants reported OA. Older age (odds ratio (OR)(70-79 vs 50-59)=2.69, 95% confidence interval (CI)=2.60-2.78) and higher body mass index (BMI) (OR(BMI>or=40.0 vs or=30.0) was 57.9% in African Americans, 51.0% in American Indians, 41.9% in Hispanic whites, and 32.9% in non-Hispanic whites. The prevalence of other major OA risk factors was higher in African-American, American-Indian, and Hispanic white women than in non-Hispanic white women. Non-Hispanic white women who were in the extreme obese category (BMI>or=40.0 kg/m(2)) had a 2.80 times (95% CI=2.63, 2.99) greater odds of self-reported OA. The odds were even higher in American-Indian (OR=4.22, 95% CI=1.82, 9.77) and African-American (OR=3.31, 95% CI=2.79, 3.91) women, indicating a significant interactive effect of BMI and ethnicity on odds of OA. In conclusion, OA is a highly prevalent condition in postmenopausal women, and there are differential effects according to ethnicity.

  3. Synthesis and characterization of poly(acrylic acid)-g-sodium alginate hydrogel initiated by gamma irradiation for controlled release of chlortetracycline HCl

    International Nuclear Information System (INIS)

    Mohamed, S.F.; Mahmoud, G.A.; Taleb, M.F.A.

    2013-01-01

    pH-Sensitive hydrogel was synthesized by gamma radiation crosslinking for sodium alginate extracted from the marine brown alga Turbinaria decurrens and acrylic acid. Preparation of the hydrogels involved free radical polymerization of a combination of acrylic acid (w = 0.2) and different contents of sodium alginate (w = 0.05, 0.10, and 0.15) in aqueous solution using gamma rays of a 60 Co source at an irradiation dose rate of 1.2 kGy/h. The swelling behavior of the prepared hydrogel was determined by investigating the swelling time, pH of medium, and alginate content in the hydrogel. The results showed that the hydrogel reached the equilibrium swelling state in water after 6 h. The hydrogel was found to be pH responsive. The drug loading and in vitro release properties of the hydrogel were also evaluated using chlortetracycline hydrochloride as the model drug. The adsorption isotherm studies by batching techniques under the effect of different initial feed concentrations of drug, different pH values, and different sodium alginate content of the adsorbent hydrogel were investigated. The diffusion of chlortetracycline hydrochloride within the hydrogel was found to be of non-Fickian character. The kinetic parameters such as the diffusion exponent, diffusion constant, and diffusion coefficient were also evaluated. (author)

  4. Platelet-activating factor synthesis and receptor-mediated signaling are downregulated in ovine newborn lungs: relevance in postnatal pulmonary adaptation and persistent pulmonary hypertension of the newborn.

    Science.gov (United States)

    Renteria, L S; Cruz, E; Ibe, B O

    2013-12-01

    Platelet-activating factor (PAF) is a phospholipid with a wide range of biological activities. We studied PAF metabolism and PAF receptor (PAFR) signaling in perinatal ovine lungs to understand PAF's role in transition of the perinatal pulmonary hemodynamics and pathophysiology of persistent pulmonary hypertension of the newborn. We hypothesized that downregulation of PAF synthesis with upregulation of PAF catabolism by acetylhydrolase (PAF-Ah) in the newborn lung is needed for fetus-to-newborn pulmonary adaptation. Studies were conducted on fetal and newborn lamb pulmonary arteries (PA), veins (PV) and smooth muscle cells (SMC). PAF metabolism, PAFR binding and cell proliferation were studied by cell culture; gene expression was studied by qPCR. Fetal lungs synthesized 60% more PAF than newborn lungs. Compared with the fetal PVs and SMCs, PAF-Ah activity in newborn was 40-60% greater. PAF-Ah mRNA expression in newborn vessels was different from the expression by fetal PA. PAF-Ah gene clone activity confirmed deletion of hypoxia-sensitive site. PAFR mRNA expression by the PVs and SMC-PV of the fetus and newborn was greater than by corresponding PAs and SMC-PA. Q-PCR study of PAFR expression by the SMC-PV of both groups was greater than SMC-PA. Fetal SMCs bound more PAF than the newborn SMCs. PAFR antagonist, CV-3988, inhibited PAFR binding and DNA synthesis by the fetal SMCs, but augmented binding and DNA synthesis by newborn cells. We show different PAF-PAFR mediated effects in perinatal lungs, suggesting both transcriptional and translational regulation of PAF-Ah and PAFR expression in the perinatal lamb lungs. These indicate that the downregulation of PAF-mediated effects postnatally protects against persistent pulmonary hypertension of the newborn.

  5. Endoplasmic Reticulum Stress Induced Synthesis of a Novel Viral Factor Mediates Efficient Replication of Genotype-1 Hepatitis E Virus.

    Directory of Open Access Journals (Sweden)

    Vidya P Nair

    2016-04-01

    Full Text Available Hepatitis E virus (HEV causes acute hepatitis in many parts of the world including Asia, Africa and Latin America. Though self-limiting in normal individuals, it results in ~30% mortality in infected pregnant women. It has also been reported to cause acute and chronic hepatitis in organ transplant patients. Of the seven viral genotypes, genotype-1 virus infects humans and is a major public health concern in South Asian countries. Sporadic cases of genotype-3 and 4 infection in human and animals such as pigs, deer, mongeese have been reported primarily from industrialized countries. Genotype-5, 6 and 7 viruses are known to infect animals such as wild boar and camel, respectively. Genotype-3 and 4 viruses have been successfully propagated in the laboratory in mammalian cell culture. However, genotype-1 virus replicates poorly in mammalian cell culture and no other efficient model exists to study its life cycle. Here, we report that endoplasmic reticulum (ER stress promotes genotype-1 HEV replication by inducing cap-independent, internal initiation mediated translation of a novel viral protein (named ORF4. Importantly, ORF4 expression and stimulatory effect of ER stress inducers on viral replication is specific to genotype-1. ORF4 protein sequence is mostly conserved among genotype-1 HEV isolates and ORF4 specific antibodies were detected in genotype-1 HEV patient serum. ORF4 interacted with multiple viral and host proteins and assembled a protein complex consisting of viral helicase, RNA dependent RNA polymerase (RdRp, X, host eEF1α1 (eukaryotic elongation factor 1 isoform-1 and tubulinβ. In association with eEF1α1, ORF4 stimulated viral RdRp activity. Furthermore, human hepatoma cells that stably express ORF4 or engineered proteasome resistant ORF4 mutant genome permitted enhanced viral replication. These findings reveal a positive role of ER stress in promoting genotype-1 HEV replication and pave the way towards development of an efficient

  6. Mechanism and Regulation of Protein Synthesis in Saccharomyces cerevisiae

    Science.gov (United States)

    Dever, Thomas E.; Kinzy, Terri Goss; Pavitt, Graham D.

    2016-01-01

    In this review, we provide an overview of protein synthesis in the yeast Saccharomyces cerevisiae. The mechanism of protein synthesis is well conserved between yeast and other eukaryotes, and molecular genetic studies in budding yeast have provided critical insights into the fundamental process of translation as well as its regulation. The review focuses on the initiation and elongation phases of protein synthesis with descriptions of the roles of translation initiation and elongation factors that assist the ribosome in binding the messenger RNA (mRNA), selecting the start codon, and synthesizing the polypeptide. We also examine mechanisms of translational control highlighting the mRNA cap-binding proteins and the regulation of GCN4 and CPA1 mRNAs. PMID:27183566

  7. Measuring trauma and stressful events in childhood and adolescence among patients with first-episode psychosis: initial factor structure, reliability, and validity of the Trauma Experiences Checklist.

    Science.gov (United States)

    Cristofaro, Sarah L; Cleary, Sean D; Ramsay Wan, Claire; Broussard, Beth; Chapman, Colby; Haggard, Patrick J; Jananeh, Sara; Myers, Neely L; Compton, Michael T

    2013-12-15

    Past trauma and stressful events, especially in childhood and adolescence, are common among individuals with serious mental illnesses like schizophrenia. Traumatic experiences are thought to be a socio-environmental risk factor not only for poorer outcomes, but also potentially for the onset of these disorders. Because improved measurement tools are needed, we developed and studied, among 205 first-episode psychosis patients, the factor structure, internal consistency reliability, and initial validity of the Trauma Experiences Checklist (TEC), our measure of trauma and stressful events during childhood/adolescence. We assessed validity of subscales using correlations with Childhood Trauma Questionnaire-Short Form, Parental Harsh Discipline, Violence Exposure, and TEC-Informant Version scores. Exploratory factor analysis resulted in two internally consistent subscales (Cronbach's α=0.79 and 0.80, respectively), interpersonal abuse and family stress, and violence, death, and legal involvement. Scores from the former subscale were substantially associated with CTQ-SF physical, emotional, and sexual abuse (r=0.42-0.57, all pchildhood and adolescence. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Coronal tibiofemoral subluxation is not an independent risk factor for total knee arthroplasty in patients with moderate to severe varus-osteoarthritis: data from the "Osteoarthritis Initiative".

    Science.gov (United States)

    Schadler, Paul; Kasparek, Max; Boettner, Fritz; Sgroi, Mirco; Faschingbauer, Martin

    2017-10-01

    Only few prognostic factors for progression of knee osteoarthritis are well established, including varus malalignment. The purpose of this study was to evaluate whether coronal tibiofemoral subluxation is a predictor for total knee arthroplasty. Patients from the progression subcohort of the longitudinal database "Osteoarthritis Initiative" with moderate to severe osteoarthritis and varus malalignment of greater than 3 degrees were included. Patients who underwent total knee arthroplasty were matched with patients treated conservatively. Subluxation was measured on full limb length X-rays. Cox regression analysis was performed to retrospectively evaluate subluxation as a risk factor for total knee arthroplasty and check for a possible association between subluxation and pain at the beginning of the observation period in this study. A total of 215 patients were included. Cox regression demonstrated that varus malalignment increased the hazard to undergo surgery by 16% (HR 1.158, p = 0.008) while subluxation did not (HR 1.12, p = 0.11). Furthermore, subluxation was neither associated with poor WOMAC (OR 1.13, p = 0.194) nor KOOS (OR 1.11, p = 0.256) knee pain scores at the beginning of the observation period. The results presented show that subluxation is neither an independent risk factor for total knee arthroplasty, nor for poor pain scores. III.

  9. Reasons and Risk Factors for the Initial Regimen Modification in Chinese Treatment-Naive Patients with HIV Infection: A Retrospective Cohort Analysis.

    Directory of Open Access Journals (Sweden)

    Jianjun Sun

    Full Text Available To investigate the reasons and risk factors for modification of the first combined antiretroviral therapy (cART currently used for HIV infected patients who were treatment naïve in Shanghai China.Making a retrospective observational research on treatment naïve patients with HIV infection who initiated cART during the period of September 1st 2005---December 1st 2013. The demographic and clinical data were collected from the first visit to the time of the first regimen modification or the last visit in December 1st, 2014. The reasons of treatment modification were recorded. Survival analysis of modification was made by Kaplan-Meier curves analysis and log rank test, and a Cox multiple regression model was constructed to identify related factors of modification.A total number of the eligible participants were 3372 and 871(25.8% patients changed their first cART regimen. The median follow up was 22 months [interquartile range (IQR 14-39]. Among patients who modified the original regimen, drug toxicity occurred in 805(92.4% participants and 44(5.1% experienced treatment failure. In multiple regression analysis regimen modification was associated with patients' age more than 40 years old (aHR 1.224, 95%CI 1.051-1.426, P = 0.010, CD4 less than 200(aHR 1.218, 95%CI 1.044-1.421, P = 0.012 and the initial regimen they received. Compared with the regimen of TDF+3TC+EFV, patients with regimen of d4T+3TC+NVP, d4T+3TC+EFV, AZT+3TC+NVP or AZT+3TC+EFV were 10.4, 8.2, 6.4, 2.5 times more likely to modify their initial regimen, respectively.The main reason for the regimen switch was drug toxicity and main risk factors for regimen modification were age older than 40 years, CD4 cell counts less than 200 at baseline and regimen they received. Among the 2NRTI plus 1NNRTI regimens, the co-formulation of d4T+3TC+NVP had the highest risk for modification while the regimen of TDF+3TC+EFV was the most tolerable treatment regimen in first years' follow up.

  10. Factors associated with initial treatment and survival for clinically localized prostate cancer: results from the CDC-NPCR Patterns of Care Study (PoC1)

    International Nuclear Information System (INIS)

    Schymura, Maria J; Kahn, Amy R; German, Robert R; Hsieh, Mei-Chin; Cress, Rosemary D; Finch, Jack L; Fulton, John P; Shen, Tiefu; Stuckart, Erik

    2010-01-01

    Despite the large number of men diagnosed with localized prostate cancer, there is as yet no consensus concerning appropriate treatment. The purpose of this study was to describe the initial treatment patterns for localized prostate cancer in a population-based sample and to determine the clinical and patient characteristics associated with initial treatment and overall survival. The analysis included 3,300 patients from seven states, diagnosed with clinically localized prostate cancer in 1997. We examined the association of sociodemographic and clinical characteristics with four treatment options: radical prostatectomy, radiation therapy, hormone therapy, and watchful waiting. Diagnostic and treatment information was abstracted from medical records. Socioeconomic measures were derived from the 2000 Census based on the patient's residence at time of diagnosis. Vital status through December 31, 2002, was obtained from medical records and linkages to state vital statistics files and the National Death Index. Multiple logistic regression analysis and Cox proportional hazards models identified factors associated with initial treatment and overall survival, respectively. Patients with clinically localized prostate cancer received the following treatments: radical prostatectomy (39.7%), radiation therapy (31.4%), hormone therapy (10.3%), or watchful waiting (18.6%). After multivariable adjustment, the following variables were associated with conservative treatment (hormone therapy or watchful waiting): older age, black race, being unmarried, having public insurance, having non-screen detected cancer, having normal digital rectal exam results, PSA values above 20, low Gleason score (2-4), comorbidity, and state of residence. Among patients receiving definitive treatment (radical prostatectomy or radiation therapy), older age, being unmarried, PSA values above 10, unknown Gleason score, state of residence, as well as black race in patients under 60 years of age, were

  11. Factors associated with initial treatment and survival for clinically localized prostate cancer: results from the CDC-NPCR Patterns of Care Study (PoC1

    Directory of Open Access Journals (Sweden)

    Fulton John P

    2010-04-01

    Full Text Available Abstract Background Despite the large number of men diagnosed with localized prostate cancer, there is as yet no consensus concerning appropriate treatment. The purpose of this study was to describe the initial treatment patterns for localized prostate cancer in a population-based sample and to determine the clinical and patient characteristics associated with initial treatment and overall survival. Methods The analysis included 3,300 patients from seven states, diagnosed with clinically localized prostate cancer in 1997. We examined the association of sociodemographic and clinical characteristics with four treatment options: radical prostatectomy, radiation therapy, hormone therapy, and watchful waiting. Diagnostic and treatment information was abstracted from medical records. Socioeconomic measures were derived from the 2000 Census based on the patient's residence at time of diagnosis. Vital status through December 31, 2002, was obtained from medical records and linkages to state vital statistics files and the National Death Index. Multiple logistic regression analysis and Cox proportional hazards models identified factors associated with initial treatment and overall survival, respectively. Results Patients with clinically localized prostate cancer received the following treatments: radical prostatectomy (39.7%, radiation therapy (31.4%, hormone therapy (10.3%, or watchful waiting (18.6%. After multivariable adjustment, the following variables were associated with conservative treatment (hormone therapy or watchful waiting: older age, black race, being unmarried, having public insurance, having non-screen detected cancer, having normal digital rectal exam results, PSA values above 20, low Gleason score (2-4, comorbidity, and state of residence. Among patients receiving definitive treatment (radical prostatectomy or radiation therapy, older age, being unmarried, PSA values above 10, unknown Gleason score, state of residence, as well as black

  12. UAP56 is an important mediator of Angiotensin II/platelet derived growth factor induced vascular smooth muscle cell DNA synthesis and proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Sahni, Abha [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642 (United States); Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555 (United States); Wang, Nadan [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642 (United States); Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Alexis, Jeffrey, E-mail: jeffrey_alexis@urmc.rochester.edu [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642 (United States)

    2013-02-15

    Highlights: ► Knockdown of UAP56 inhibits Angiotensin II/PDGF induced vascular smooth muscle cell proliferation. ► UAP56 is a positive regulator of E2F transcriptional activation. ► UAP56 is present in the vessel wall of low flow carotid arteries. -- Abstract: Angiotensin (Ang) II and platelet-derived growth factor (PDGF) are important mediators of pathologic vascular smooth muscle cell (VSMC) proliferation. Identifying downstream mediators of Ang II and PDGF signaling may provide insights for therapies to improve vascular proliferative diseases. We have previously demonstrated that breakpoint cluster region (Bcr) is an important mediator of Ang II/PDGF signaling in VSMC. We have recently reported that the DExD/H box protein UAP56 is an interacting partner of Bcr in regulating VSMC DNA synthesis. We hypothesized that UAP56 itself is an important regulator of VSMC proliferation. In this report we demonstrate that knockdown of UAP56 inhibits Ang II/PDGF induced VSMC DNA synthesis and proliferation, and inhibits E2F transcriptional activity. In addition, we demonstrate that UAP56 is present in the vessel wall of low-flow carotid arteries. These findings suggest that UAP56 is a regulator of VSMC proliferation and identify UAP56 as a target for preventing vascular proliferative disease.

  13. Switchgrass SBP-box transcription factors PvSPL1 and 2 function redundantly to initiate side tillers and affect biomass yield of energy crop.

    Science.gov (United States)

    Wu, Zhenying; Cao, Yingping; Yang, Ruijuan; Qi, Tianxiong; Hang, Yuqing; Lin, Hao; Zhou, Gongke; Wang, Zeng-Yu; Fu, Chunxiang

    2016-01-01

    Switchgrass (Panicum virgatum L.) is a dedicated lignocellulosic feedstock for bioenergy production. The SQUAMOSA PROMOTER-BINDING PROTEIN (SBP-box)-LIKE transcription factors (SPLs) change plant architecture and vegetative-to-reproductive phase transition significantly, and as such, they are promising candidates for genetic improvement of switchgrass biomass yield. However, the genome-wide identification and functional characterization of SPL genes have yet to be investigated in herbaceous energy crops. We identified 35 full-length SPL genes in the switchgrass genome. The phylogenetic relationship and expression pattern of PvSPLs provided baseline information for their function characterization. Based on the global overview of PvSPLs, we explored the biological function of miR156-targeted PvSPL1 and PvSPL2, which are closely related members of SPL family in switchgrass. Our results showed that PvSPL1 and PvSPL2 acted redundantly to modulate side tiller initiation, whereas they did not affect phase transition and internode initiation. Consistently, overexpression of the miR156-resistant rPvSPL2 in the miR156-overexpressing transgenic plants greatly reduced tiller initiation, but did not rescue the delayed flowering and increased internode numbers. Furthermore, suppression of PvSPL2 activity in switchgrass increased biomass yield and reduced lignin accumulation, which thereby elevated the total amount of solubilized sugars. Our results indicate that different miR156-targeted PvSPL subfamily genes function predominantly in certain biological processes in switchgrass. We suggest that PvSPL2 and its paralogs can be utilized as the valuable targets in molecular breeding of energy crops for developing novel germplasms with high biofuel production.

  14. The theory-practice relationship: reflective skills and theoretical knowledge as key factors in bridging the gap between theory and practice in initial nursing education.

    Science.gov (United States)

    Hatlevik, Ida Katrine Riksaasen

    2012-04-01

    This paper is a report of a correlational study of the relations of nursing students' acquired reflective skills, practical skills and theoretical knowledge on their perception of coherence between theory and practice. Reflection is considered a key factor in bridging the gap between theory and practice. However, it is not evident whether reflective skills are primarily generic in nature or whether they develop from a theoretical knowledge base or the acquisition of practical skills. This study is a secondary analysis of existing data. The data are part of a student survey that was conducted among third-year nursing students in Norway during the spring of 2007. A total of 446 nursing students participated in this study and the response rate was 71%. Structural equation modelling analyses were performed. The results indicate that students' perception of coherence between theory and practice during initial nursing education is directly influenced by reflective skills and theoretical knowledge. The results also reveal that reflective skills have mediating effects and that practical skills have a fully mediated and theoretical knowledge a partially mediated influence on students' perception of coherence. The findings imply that helping students perceive coherence between theory and practice in nursing education, developing students' reflective skills and strengthening the theoretical components of the initial nursing education programme might be beneficial. The results suggest that reflective thinking is not merely a generic skill but rather a skill that depends on the acquisition of relevant professional knowledge and experience. © 2011 Blackwell Publishing Ltd.

  15. Interaction of the RNP1 motif in PRT1 with HCR1 promotes 40S binding of eukaryotic initiation factor 3 in yeast

    DEFF Research Database (Denmark)

    Nielsen, Klaus H; Valásek, Leos; Sykes, Caroah

    2006-01-01

    We found that mutating the RNP1 motif in the predicted RRM domain in yeast eukaryotic initiation factor 3 (eIF3) subunit b/PRT1 (prt1-rnp1) impairs its direct interactions in vitro with both eIF3a/TIF32 and eIF3j/HCR1. The rnp1 mutation in PRT1 confers temperature-sensitive translation initiation...... impairs the 40S binding of eIF3 more so than the 40S binding of HCR1; (iii) overexpressing HCR1-R215I decreases the Ts(-) phenotype and increases 40S-bound eIF3 in rnp1 cells; (iv) the rnp1 Ts(-) phenotype is exacerbated by tif32-Delta6, which eliminates a binding determinant for HCR1 in TIF32; and (v......) hcr1Delta impairs 40S binding of eIF3 in otherwise wild-type cells. Interestingly, rnp1 also reduces the levels of 40S-bound eIF5 and eIF1 and increases leaky scanning at the GCN4 uORF1. Thus, the PRT1 RNP1 motif coordinates the functions of HCR1 and TIF32 in 40S binding of eIF3 and is needed...

  16. Asymmetric synthesis v.4

    CERN Document Server

    Morrison, James

    1984-01-01

    Asymmetric Synthesis, Volume 4: The Chiral Carbon Pool and Chiral Sulfur, Nitrogen, Phosphorus, and Silicon Centers describes the practical methods of obtaining chiral fragments. Divided into five chapters, this book specifically examines initial chiral transmission and extension. The opening chapter describes the so-called chiral carbon pool, the readily available chiral carbon fragments used as building blocks in synthesis. This chapter also provides a list of 375 chiral building blocks, along with their commercial sources, approximate prices, and methods of synthesis. Schemes involving

  17. Utility of combinations of biomarkers, cognitive markers, and risk factors to predict conversion from mild cognitive impairment to Alzheimer disease in patients in the Alzheimer's disease neuroimaging initiative.

    Science.gov (United States)

    Gomar, Jesus J; Bobes-Bascaran, Maria T; Conejero-Goldberg, Concepcion; Davies, Peter; Goldberg, Terry E

    2011-09-01

    Biomarkers have become increasingly important in understanding neurodegenerative processes associated with Alzheimer disease. Markers include regional brain volumes, cerebrospinal fluid measures of pathological Aβ1-42 and total tau, cognitive measures, and individual risk factors. To determine the discriminative utility of different classes of biomarkers and cognitive markers by examining their ability to predict a change in diagnostic status from mild cognitive impairment to Alzheimer disease. Longitudinal study. We analyzed the Alzheimer's Disease Neuroimaging Initiative database to study patients with mild cognitive impairment who converted to Alzheimer disease (n = 116) and those who did not convert (n = 204) within a 2-year period. We determined the predictive utility of 25 variables from all classes of markers, biomarkers, and risk factors in a series of logistic regression models and effect size analyses. The Alzheimer's Disease Neuroimaging Initiative public database. Primary outcome measures were odds ratios, pseudo- R(2)s, and effect sizes. In comprehensive stepwise logistic regression models that thus included variables from all classes of markers, the following baseline variables predicted conversion within a 2-year period: 2 measures of delayed verbal memory and middle temporal lobe cortical thickness. In an effect size analysis that examined rates of decline, change scores for biomarkers were modest for 2 years, but a change in an everyday functional activities measure (Functional Assessment Questionnaire) was considerably larger. Decline in scores on the Functional Assessment Questionnaire and Trail Making Test, part B, accounted for approximately 50% of the predictive variance in conversion from mild cognitive impairment to Alzheimer disease. Cognitive markers at baseline were more robust predictors of conversion than most biomarkers. Longitudinal analyses suggested that conversion appeared to be driven less by changes in the neurobiologic

  18. The interaction of cytoplasmic poly(A)-binding protein with eukaryotic initiation factor 4G suppresses nonsense-mediated mRNA decay.

    Science.gov (United States)

    Fatscher, Tobias; Boehm, Volker; Weiche, Benjamin; Gehring, Niels H

    2014-10-01

    Nonsense-mediated mRNA decay (NMD) eliminates different classes of mRNA substrates including transcripts with long 3' UTRs. Current models of NMD suggest that the long physical distance between the poly(A) tail and the termination codon reduces the interaction between cytoplasmic poly(A)-binding protein (PABPC1) and the eukaryotic release factor 3a (eRF3a) during translation termination. In the absence of PABPC1 binding, eRF3a recruits the NMD factor UPF1 to the terminating ribosome, triggering mRNA degradation. Here, we have used the MS2 tethering system to investigate the suppression of NMD by PABPC1. We show that tethering of PABPC1 between the termination codon and a long 3' UTR specifically inhibits NMD-mediated mRNA degradation. Contrary to the current model, tethered PABPC1 mutants unable to interact with eRF3a still efficiently suppress NMD. We find that the interaction of PABPC1 with eukaryotic initiation factor 4G (eIF4G), which mediates the circularization of mRNAs, is essential for NMD inhibition by tethered PABPC1. Furthermore, recruiting either eRF3a or eIF4G in proximity to an upstream termination codon antagonizes NMD. While tethering of an eRF3a mutant unable to interact with PABPC1 fails to suppress NMD, tethered eIF4G inhibits NMD in a PABPC1-independent manner, indicating a sequential arrangement of NMD antagonizing factors. In conclusion, our results establish a previously unrecognized link between translation termination, mRNA circularization, and NMD suppression, thereby suggesting a revised model for the activation of NMD at termination codons upstream of long 3' UTR. © 2014 Fatscher et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  19. Thermodynamic Factors Affecting UC1-xNxIrradiation and Synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Lindemer, T.B.

    2005-04-22

    There is interest in attempting to synthesize nearly pure uranium nitride (UN) kernels for high-temperature gas-cooled reactor (HTGR) fuel. Because the proposed process involves carbothermic conversion of a urania-carbon mixture in nitrogen and because there is a complete ideal solution of uranium carbide (UC) and UN, which is written as UC{sub 1-x}N{sub x}, the practical value of x for fuel irradiation needs to be determined. Insight is to be gained by relevant thermodynamic calculations of carbide-nitride equilibria for the fuel and fission product systems. The equilibria are readily compared on the nitrogen-based Ellingham diagram, which, in turn, provides guidance in interpreting past irradiations and in synthesis of the UC{sub 1-x}N{sub x} kernels.

  20. Factors that influence the provision of intrapartum and postnatal care by skilled birth attendants in low- and middle-income countries: a qualitative evidence synthesis

    Science.gov (United States)

    Munabi-Babigumira, Susan; Glenton, Claire; Lewin, Simon; Fretheim, Atle; Nabudere, Harriet

    2017-01-01

    -income countries. Data collection and analysis One review author extracted data and assessed study quality, and another review author checked the data. We synthesised data using the best fit framework synthesis approach and assessed confidence in the evidence using the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach. We used a matrix approach to explore whether the factors identified by health workers in our synthesis as important for providing maternity care were reflected in the interventions evaluated in the studies in a related intervention review. Main results We included 31 studies that explored the views and experiences of different types of SBAs, including doctors, midwives, nurses, auxiliary nurses and their managers. The included studies took place in Africa, Asia, and Latin America. Our synthesis pointed to a number of factors affecting SBAs’ provision of quality care. The following factors were based on evidence assessed as of moderate to high confidence. Skilled birth attendants reported that they were not always given sufficient training during their education or after they had begun clinical work. Also, inadequate staffing of facilities could increase the workloads of skilled birth attendants, make it difficult to provide supervision and result in mothers being offered poorer care. In addition, SBAs did not always believe that their salaries and benefits reflected their tasks and responsibilities and the personal risks they undertook. Together with poor living and working conditions, these issues were seen to increase stress and to negatively affect family life. Some SBAs also felt that managers lacked capacity and skills, and felt unsupported when their workplace concerns were not addressed. Possible causes of staff shortages in facilities included problems with hiring and assigning health workers to facilities where they were needed; lack of funding; poor management and bureaucratic systems; and low salaries. Skilled

  1. Factors associated with the disposition of severely injured patients initially seen at non–trauma center emergency departments: disparities by insurance status.

    Science.gov (United States)

    Delgado, M Kit; Yokell, Michael A; Staudenmayer, Kristan L; Spain, David A; Hernandez-Boussard, Tina; Wang, N Ewen

    2014-05-01

    Trauma is the leading cause of potential years of life lost before age 65 years in the United States. Timely care in a designated trauma center has been shown to reduce mortality by 25%. However, many severely injured patients are not transferred to trauma centers after initially being seen at non–trauma center emergency departments (EDs). To determine patient-level and hospital-level factors associated with the decision to admit rather than transfer severely injured patients who are initially seen at non–trauma center EDs and to ascertain whether insured patients are more likely to be admitted than transferred compared with uninsured patients. Retrospective analysis of the 2009 Nationwide Emergency Department Sample. We included all ED encounters for major trauma (Injury Severity Score, >15) seen at non–trauma centers in patients aged 18 to 64 years. We excluded ED discharges and ED deaths. We quantified the absolute risk difference between admission vs transfer by insurance status, while adjusting for age, sex, mechanism of injury, Injury Severity Score, weekend admission and month of visit, and urban vs rural status and median household income of the home zip code, as well as annual ED visit volume and teaching status and US region. Inpatient admission vs transfer to another acute care facility. In 2009, a total of 4513 observations from 636 non–trauma center EDs were available for analysis, representing a nationally weighted population of 19,312 non–trauma center ED encounters for major trauma. Overall, 54.5% in 2009 were admitted to the non–trauma center. Compared with patients without insurance, the adjusted absolute risk of admission vs transfer was 14.3% (95% CI, 9.2%-19.4%) higher for patients with Medicaid and 11.2% (95% CI, 6.9%-15.4%) higher for patients with private insurance. Other factors associated with admission vs transfer included severe abdominal injuries (risk difference, 15.9%; 95% CI, 9.4%-22.3%), urban teaching hospital vs non

  2. Risk factors influencing the outcome of peptic ulcer bleeding in chronic kidney disease after initial endoscopic hemost