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Sample records for factor daf cd55

  1. Equilibrium and kinetics of Sin Nombre hantavirus binding at DAF/CD55 functionalized bead surfaces.

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    Buranda, Tione; Swanson, Scarlett; Bondu, Virginie; Schaefer, Leah; Maclean, James; Mo, Zhenzhen; Wycoff, Keith; Belle, Archana; Hjelle, Brian

    2014-03-10

    Decay accelerating factor (DAF/CD55) is targeted by many pathogens for cell entry. It has been implicated as a co-receptor for hantaviruses. To examine the binding of hantaviruses to DAF, we describe the use of Protein G beads for binding human IgG Fc domain-functionalized DAF ((DAF)₂-Fc). When mixed with Protein G beads the resulting DAF beads can be used as a generalizable platform for measuring kinetic and equilibrium binding constants of DAF binding targets. The hantavirus interaction has high affinity (24-30 nM; k(on) ~ 10⁵ M⁻¹ s⁻¹, k(off) ~ 0.0045 s⁻¹). The bivalent (DAF)₂-Fc/SNV data agree with hantavirus binding to DAF expressed on Tanoue B cells (K(d) = 14.0 nM). Monovalent affinity interaction between SNV and recombinant DAF of 58.0 nM is determined from competition binding. This study serves a dual purpose of presenting a convenient and quantitative approach of measuring binding affinities between DAF and the many cognate viral and bacterial ligands and providing new data on the binding constant of DAF and Sin Nombre hantavirus. Knowledge of the equilibrium binding constant allows for the determination of the relative fractions of bound and free virus particles in cell entry assays. This is important for drug discovery assays for cell entry inhibitors.

  2. Nitric oxide induces segregation of decay accelerating factor (DAF or CD55) from the membrane lipid-rafts and its internalization in human endometrial cells.

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    Banadakoppa, Manu; Goluszko, Pawel; Liebenthal, Daniel; Yallampalli, Chandra

    2012-10-01

    Recent studies suggest that DAF (decay accelerating factor), a complement regulatory protein, present in lipid rafts, is utilized by Dr fimbriated Escherichia coli for their binding and internalization. Previous studies in our laboratory have shown that NO (nitric oxide) can reduce the invasion of Dr(+) E. coli and the severity of uterine infection in pregnant rats. Also, the expression level of DAF both at the mRNA and protein levels has been shown to be reduced by NO. Therefore NO mediated down-regulation of DAF appears to be an important factor in reducing the susceptibility to E. coli infection. However, it is unclear if NO can actually modulate the membrane association of DAF and therefore initial bacterial binding to cells. We found that NO induces the delocalization of DAF from the G(M1)-rich lipid rafts. Using biochemical and cell biological approaches in a uterine epithelial cell model (Ishikawa cells), DAF accumulates in caveolae upon exposure to NO. Interaction of DAF with the caveolar protein, caveolin1, leads to their internalization by endosomes. NO-induced delocalization of DAF from the lipid raft and its accumulation in caveolae are mediated through a cGMP (cyclic guanosine monophosphate) pathway. The acute localized synthesis of NO and its influence on DAF localization may represent an important unrecognized phenomenon of host defence against Dr(+) E. coli bacteria, as well as many disease conditions that involve complement system.

  3. Role of transcription factor Sp1 and RNA binding protein HuR in the downregulation of Dr+ Escherichia coli receptor protein decay accelerating factor (DAF or CD55) by nitric oxide.

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    Banadakoppa, Manu; Liebenthal, Daniel; Nowak, David E; Urvil, Petri; Yallampalli, Uma; Wilson, Gerald M; Kishor, Aparna; Yallampalli, Chandra

    2013-02-01

    We previously reported that nitric oxide (NO) reduces the rate of bacteremia and maternal mortality in pregnant rats with uterine infection by Escherichia coli expressing the Dr Fimbria (Dr(+) ). The epithelial invasion of Dr(+) E. coli is dependent on the expression level of its cellular receptor decay accelerating factor (DAF). NO reduces the rate of bacteremia by downregulating the expression of DAF. In this study, we elucidated the role of transcription factor Sp1 and RNA binding protein HuR in the downregulation of human DAF by NO. We generated a series of deletion mutant constructs of DAF gene 5'-untranslated region and mapped the NO-response region upstream to the core promoter region of the DAF gene. One of the several Sp1 binding sites in the DAF 5'-untranslated region was located within the NO-response region. The binding of Sp1 to this site was inhibited by NO. Furthermore, NO also promoted the degradation of DAF mRNA. The 3'-untranslated region of DAF harbors an AU-rich element and this element destabilized the mRNA transcript. NO promoted the rapid degradation of DAF mRNA by inhibiting the binding of mRNA stabilizing protein HuR to this AU-rich region. The inhibition of binding of HuR to the AU-rich region was due to the S-nitrosylation of one or more cysteine residues by NO. Thus, these data reveal the molecular mediators of transcriptional and post-transcriptional regulation of DAF by NO with implications in pathophysiology related to DAF. © 2012 The Authors Journal compilation © 2012 FEBS.

  4. Decay Accelerating Factor (CD55) Protects Neuronal Cells from Chemical Hypoxia-Induced Injury

    Science.gov (United States)

    2010-04-09

    Pavlakovic G, Isom GE: Dopaminergic neurotoxicity of cyanide: neurochemical, histological and behavioral characterization. Toxicol Appl Pharmacol...provided the original work is properly cited. ResearchDecay accelerating factor (CD55) protects neuronal cells from chemical hypoxia-induced injury...deposition of C3a/C5a and membrane attack complex (MAC or C5b-9) production. The present study investigates the ability of DAF to protect primary cultured

  5. The Expression and Action of Decay-Accelerating Factor (CD55 in Human Malignancies and Cancer Therapy

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    Jan-Henrik Mikesch

    2006-01-01

    Full Text Available Decay-accelerating factor (DAF, CD55 is physiologically acting as an inhibitor of the complement system, but is also broadly expressed in malignant tumours. Here DAF seems to exert different functions beyond its immunological role such as e.g. promotion of tumorigenesis, decrease of complement mediated tumor cell lysis, autocrine loops for cell rescue and evasion of apoptosis, neoangiogenesis, invasiveness, cell motility, and metastasis via oncogenic tyrosine kinase pathways and specific seven-span transmembrane receptors (CD97 binding. Therefore, DAF has already become a target for therapy. In this paper we review the role of DAF in human malignancies as described in different basic, diagnostic and experimental therapeutic studies.

  6. A single amino acid substitution controls DAF-dependent phenotype of echovirus 11 in rhabdomyosarcoma cells.

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    Novoselov, Alexey V; Rezaykin, Alexey V; Sergeev, Alexander G; Fadeyev, Fedor A; Grigoryeva, Julia V; Sokolova, Zoya I

    2012-06-01

    Decay accelerating factor (DAF, CD55) is used by DAF-dependent (Daf+) variants of echovirus 11 (EV11) as a primary cellular receptor. The interaction of EV11 with DAF is completely reversible, therefore DAF-dependent variants require an unidentified coreceptor to initiate uncoating. Daf- variants of EV11, which do not interact with DAF, use an alternative primary cellular receptor. The aim of this study was to test the hypothesis whether the coreceptor, which is necessary for the uncoating of DAF-dependent variants, may act as an alternative primary receptor for the Daf- variants of EV11. By using the model of the two closely related daf+ and daf- clones of EV11 in rhabdomyosarcoma (RD) cell line, it was shown that a single amino acid substitution in the capsid protein VP2 could control the expression of the DAF-dependent phenotype. Anti-DAF monoclonal antibody has blocked the infection of RD cells by the DAF-dependent daf+ clone, but not by the daf- clone of EV11. Since the structural proteins of the two clones differed only in the receptor binding site for DAF, the unidentified non-DAF primary receptor for the daf- clone might have the same conformation as the uncoating coreceptor required for the daf+ clone. Despite the difference in primary receptors, both daf+ and daf- clones were equally inhibited by a monoclonal antibody to beta2-microglobulin. The monoclonal antibody B9.12.1 to class I human leukocyte antigen molecules showed no inhibitory effect in regards to either clone. The hypothesis of convergent intracellular traffic of Daf+ and Daf- variants of EV11 is discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. DAF-16/FOXO Transcription Factor in Aging and Longevity.

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    Sun, Xiaojuan; Chen, Wei-Dong; Wang, Yan-Dong

    2017-01-01

    Aging is associated with age-related diseases and an increase susceptibility of cancer. Dissecting the molecular mechanisms that underlie aging and longevity would contribute to implications for preventing and treating the age-dependent diseases or cancers. Multiple signaling pathways such as the insulin/IGF-1 signaling pathway, TOR signaling, AMPK pathway, JNK pathway and germline signaling have been found to be involved in aging and longevity. And DAF-16/FOXO, as a key transcription factor, could integrate different signals from these pathways to modulate aging, and longevity via shuttling from cytoplasm to nucleus. Hence, understanding how DAF-16/FOXO functions will be pivotal to illustrate the processes of aging and longevity. Here, we summarized how DAF-16/FOXO receives signals from these pathways to affect aging and longevity. We also briefly discussed the transcriptional regulation and posttranslational modifications of DAF-16/FOXO, its co-factors as well as its potential downstream targets participating in lifespan according to the published data in C. elegans and in mammals, and in most cases, we may focus on the studies in C. elegans which has been considered to be a very good animal model for longevity research.

  8. The DAF-16/FOXO transcription factor functions as a regulator of epidermal innate immunity.

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    Zou, Cheng-Gang; Tu, Qiu; Niu, Jie; Ji, Xing-Lai; Zhang, Ke-Qin

    2013-01-01

    The Caenorhabditis elegans DAF-16 transcription factor is critical for diverse biological processes, particularly longevity and stress resistance. Disruption of the DAF-2 signaling cascade promotes DAF-16 activation, and confers resistance to killing by pathogenic bacteria, such as Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. However, daf-16 mutants exhibit similar sensitivity to these bacteria as wild-type animals, suggesting that DAF-16 is not normally activated by these bacterial pathogens. In this report, we demonstrate that DAF-16 can be directly activated by fungal infection and wounding in wild-type animals, which is independent of the DAF-2 pathway. Fungal infection and wounding initiate the Gαq signaling cascade, leading to Ca(2+) release. Ca(2+) mediates the activation of BLI-3, a dual-oxidase, resulting in the production of reactive oxygen species (ROS). ROS then activate DAF-16 through a Ste20-like kinase-1/CST-1. Our results indicate that DAF-16 in the epidermis is required for survival after fungal infection and wounding. Thus, the EGL-30-Ca(2+)-BLI-3-CST-1-DAF-16 signaling represents a previously unknown pathway to regulate epidermal damage response.

  9. Production of multiple transgenic Yucatan miniature pigs expressing human complement regulatory factors, human CD55, CD59, and H-transferase genes.

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    Young-Hee Jeong

    Full Text Available The present study was conducted to generate transgenic pigs coexpressing human CD55, CD59, and H-transferase (HT using an IRES-mediated polycistronic vector. The study focused on hyperacute rejection (HAR when considering clinical xenotransplantation as an alternative source for human organ transplants. In total, 35 transgenic cloned piglets were produced by somatic cell nuclear transfer (SCNT and were confirmed for genomic integration of the transgenes from umbilical cord samples by PCR analysis. Eighteen swine umbilical vein endothelial cells (SUVEC were isolated from umbilical cord veins freshly obtained from the piglets. We observed a higher expression of transgenes in the transgenic SUVEC (Tg SUVEC compared with the human umbilical vein endothelial cells (HUVEC. Among these genes, HT and hCD59 were expressed at a higher level in the tested Tg organs compared with non-Tg control organs, but there was no difference in hCD55 expression between them. The transgenes in various organs of the Tg clones revealed organ-specific and spatial expression patterns. Using from 0 to 50% human serum solutions, we performed human complement-mediated cytolysis assays. The results showed that, overall, the Tg SUVEC tested had greater survival rates than did the non-Tg SUVEC, and the Tg SUVEC with higher HT expression levels tended to have more down-regulated α-Gal epitope expression, resulting in greater protection against cytotoxicity. By contrast, several Tg SUVEC with low CD55 expression exhibited a decreased resistance response to cytolysis. These results indicated that the levels of HT expression were inversely correlated with the levels of α-Gal epitope expression and that the combined expression of hCD55, hCD59, and HT proteins in SUVECs markedly enhances a protective response to human serum-mediated cytolysis. Taken together, these results suggest that combining a polycistronic vector system with SCNT methods provides a fast and efficient alternative

  10. Modulation of PBMC-decay accelerating factor (PBMC-DAF) and cytokines in rheumatoid arthritis.

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    Pahwa, Roma; Kumar, Uma; Das, Nibhriti

    2016-03-01

    Studies have suggested that abnormal expression of complement regulatory proteins and cytokines contribute significantly to the path-physiology of rheumatoid arthritis. In this context, Decay accelerating factor (DAF) a complement regulatory protein is gaining increased attention. With the notion that immune effecter mechanisms are all interlinked and circulating peripheral blood mononuclear cells (PBMCs) should have a role in a systemic disease like rheumatoid arthritis, we studied the modulation and significance of PBMC-DAF and cytokines in RA. Seventy-five RA patients and 75 healthy controls were recruited. Expression of DAF and cytokines (IFN-γ, IL-17A and IL-10) in the PBMCs of patients and controls was determined. Correlations among DAF, cytokines, and disease activity were evaluated by standard statistical methods. The effect of IFN-γ, IL-17A, and IL-10 on the expression of DAF in patients and controls was studied in vitro. Expression of PBMC-DAF declined in patients both at mRNA and surface level and correlated negatively with the disease activity. Expression of IFN-γ also declined in patients but correlated positively with DAF and negatively with disease activity. Expression of IL-17A and IL-10 was higher in patients. The levels correlated positively with disease activity and negatively with DAF both in patients and controls. In vitro studies indicated that IFN-γ up-regulated DAF expression in PBMCs, whereas IL-17A and IL-10 had negative effect on the same. The decline in the PBMC-DAF is a contributing factor in manifestations of RA. Cytokine environment contributes to this decline. These findings brought novel insights into the complement-cytokine axis in the path-physiology of RA.

  11. CAMKII and calcineurin regulate the lifespan of Caenorhabditis elegans through the FOXO transcription factor DAF-16.

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    Tao, Li; Xie, Qi; Ding, Yue-He; Li, Shang-Tong; Peng, Shengyi; Zhang, Yan-Ping; Tan, Dan; Yuan, Zengqiang; Dong, Meng-Qiu

    2013-06-25

    The insulin-like signaling pathway maintains a relatively short wild-type lifespan in Caenorhabditis elegans by phosphorylating and inactivating DAF-16, the ortholog of the FOXO transcription factors of mammalian cells. DAF-16 is phosphorylated by the AKT kinases, preventing its nuclear translocation. Calcineurin (PP2B phosphatase) also limits the lifespan of C. elegans, but the mechanism through which it does so is unknown. Herein, we show that TAX-6•CNB-1 and UNC-43, the C. elegans Calcineurin and Ca(2+)/calmodulin-dependent kinase type II (CAMKII) orthologs, respectively, also regulate lifespan through DAF-16. Moreover, UNC-43 regulates DAF-16 in response to various stress conditions, including starvation, heat or oxidative stress, and cooperatively contributes to lifespan regulation by insulin signaling. However, unlike insulin signaling, UNC-43 phosphorylates and activates DAF-16, thus promoting its nuclear localization. The phosphorylation of DAF-16 at S286 by UNC-43 is removed by TAX-6•CNB-1, leading to DAF-16 inactivation. Mammalian FOXO3 is also regulated by CAMKIIA and Calcineurin. DOI:http://dx.doi.org/10.7554/eLife.00518.001.

  12. A functional SNP in the regulatory region of the decay-accelerating factor gene associates with extraocular muscle pareses in myasthenia gravis

    KAUST Repository

    Heckmann, J M; Uwimpuhwe, H; Ballo, R; Kaur, M; Bajic, Vladimir B.; Prince, S

    2009-01-01

    Complement activation in myasthenia gravis (MG) may damage muscle endplate and complement regulatory proteins such as decay-accelerating factor (DAF) or CD55 may be protective. We hypothesize that the increased prevalence of severe extraocular

  13. The crystal structure of a coxsackievirus B3-RD variant and a refined 9-angstrom cryo-electron microscopy reconstruction of the virus complexed with decay-accelerating factor (DAF) provide a new footprint of DAF on the virus surface.

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    Yoder, Joshua D; Cifuente, Javier O; Pan, Jieyan; Bergelson, Jeffrey M; Hafenstein, Susan

    2012-12-01

    The coxsackievirus-adenovirus receptor (CAR) and decay-accelerating factor (DAF) have been identified as cellular receptors for coxsackievirus B3 (CVB3). The first described DAF-binding isolate was obtained during passage of the prototype strain, Nancy, on rhabdomyosarcoma (RD) cells, which express DAF but very little CAR. Here, the structure of the resulting variant, CVB3-RD, has been solved by X-ray crystallography to 2.74 Å, and a cryo-electron microscopy reconstruction of CVB3-RD complexed with DAF has been refined to 9.0 Å. This new high-resolution structure permits us to correct an error in our previous view of DAF-virus interactions, providing a new footprint of DAF that bridges two adjacent protomers. The contact sites between the virus and DAF clearly encompass CVB3-RD residues recently shown to be required for binding to DAF; these residues interact with DAF short consensus repeat 2 (SCR2), which is known to be essential for virus binding. Based on the new structure, the mode of the DAF interaction with CVB3 differs significantly from the mode reported previously for DAF binding to echoviruses.

  14. Expression of CD55, CD59, and CD35 on red blood cells of β-thalassaemia patients

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    Koçtekin, Belkls; Kurtoǧlu, Erdal; Yildiz, Mustafa; Bozkurt, Selen

    2017-01-01

    Aim of the study β-thalassaemia (β-Thal) is considered a severe, progressive haemolytic anaemia, which needs regular blood transfusions for life expectancy. Complement-mediated erythrocyte destruction can cause both intravascular and extravascular haemolysis. Complement regulatory proteins protect cells from such effects of the complement system. We aimed to perform quantitative analysis of membrane-bound complement regulators, CD55 (decay accelerating factorDAF), CD35 (complement receptor type 1 – CR1), and CD59 (membrane attack complex inhibitory factor – MACIF) on peripheral red blood cells by flow cytometry. Material and methods The present study was carried out on 47 β-thalassemia major (β-TM) patients, 20 β-thalassaemia intermedia (β-TI) patients, and 17 healthy volunteers as control subjects. Results CD55 levels of β-TM patients (58.64 ±17.06%) were significantly decreased compared to β-TI patients (83.34 ±13.82%) and healthy controls (88.57 ±11.69%) (p < 0.01). CD59 levels of β-TM patients were not significantly different than β-TI patients and controls, but CD35 levels were significantly lower in the β-TM patients (3.56 ±4.87%) and β-TI patients (12.48 ±9.19%) than in the control group (39.98 ±15.01%) (p < 0.01). Conclusions Low levels of CD55 and CD35 in thalassaemia major patients indicates a role for them in the aetiopathogenesis of haemolysis in this disease, and also this defect in a complement system may be responsible for the chronic complications seen in these patients. PMID:28680334

  15. An Expanded Role for the RFX Transcription Factor DAF-19, with Dual Functions in Ciliated and Nonciliated Neurons.

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    De Stasio, Elizabeth A; Mueller, Katherine P; Bauer, Rosemary J; Hurlburt, Alexander J; Bice, Sophie A; Scholtz, Sophie L; Phirke, Prasad; Sugiaman-Trapman, Debora; Stinson, Loraina A; Olson, Haili B; Vogel, Savannah L; Ek-Vazquez, Zabdiel; Esemen, Yagmur; Korzynski, Jessica; Wolfe, Kelsey; Arbuckle, Bonnie N; Zhang, He; Lombard-Knapp, Gaelen; Piasecki, Brian P; Swoboda, Peter

    2018-03-01

    Regulatory Factor X (RFX) transcription factors (TFs) are best known for activating genes required for ciliogenesis in both vertebrates and invertebrates. In humans, eight RFX TFs have a variety of tissue-specific functions, while in the worm Caenorhabditis elegans , the sole RFX gene, daf-19 , encodes a set of nested isoforms. Null alleles of daf-19 confer pleiotropic effects including altered development with a dauer constitutive phenotype, complete absence of cilia and ciliary proteins, and defects in synaptic protein maintenance. We sought to identify RFX/ daf-19 target genes associated with neuronal functions other than ciliogenesis using comparative transcriptome analyses at different life stages of the worm. Subsequent characterization of gene expression patterns revealed one set of genes activated in the presence of DAF-19 in ciliated sensory neurons, whose activation requires the daf-19c isoform, also required for ciliogenesis. A second set of genes is downregulated in the presence of DAF-19, primarily in nonsensory neurons. The human orthologs of some of these neuronal genes are associated with human diseases. We report the novel finding that daf-19a is directly or indirectly responsible for downregulation of these neuronal genes in C. elegans by characterizing a new mutation affecting the daf-19a isoform ( tm5562 ) and not associated with ciliogenesis, but which confers synaptic and behavioral defects. Thus, we have identified a new regulatory role for RFX TFs in the nervous system. The new daf-19 candidate target genes we have identified by transcriptomics will serve to uncover the molecular underpinnings of the pleiotropic effects that daf-19 exerts on nervous system function. Copyright © 2018 by the Genetics Society of America.

  16. Coating of human decay accelerating factor (hDAF) onto medical devices to improve biocompatibility.

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    Watkins, N J; Braidley, P; Bray, C J; Savill, C M; White, D J

    1997-12-01

    In passing blood through an artificial circulatory system, the blood is exposed to surfaces that result in activation of the complement system. The consequences of the activation of complement can be extremely serious for the patient ranging from mild discomfort to respiratory distress and even anaphylaxis. An entirely novel approach was to express recombinant GPI anchored human decay accelerating factor (hDAF) using the baculovirus system and then coat the recombinant protein onto the surfaces of these materials to reduce complement activation. Expression of hDAF in Sf9 cells was shown by ELISA, FACS analysis, and Western blot. Functional activity was tested by CH50 assay. For the coating experiments a small scale model of a cardiovascular bypass circuit constructed from COBE tubing was used. hDAF was either coated onto the circuit using adsorption or covalently linked via the photoreactive crosslinker, p-azidobenzoyl hydrazide. After coating, heparinised human blood was pumped around the circuit and samples were collected into EDTA collection tubes at different time points. Complement activation was measured using a Quidel C3a-des-arg EIA. The photolinked circuits gave a reduction in C3a production of 20-50%, compared to 10-20% seen with an absorbed hDAF circuit. Furthermore, the inhibition of complement was seen over the whole time scale of the photolinked circuit, 60-90 min, whilst in the adsorbed circuit inhibition was not seen to a significant degree after 60 min. The time scale of a standard cardiac bypass is 45-90 min, therefore, the photolinked circuit results are encouraging, as significant inhibition of complement activation is seen within this time frame.

  17. DAF in diabetic patients is subject to glycation/inactivation at its active site residues.

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    Flückiger, Rudolf; Cocuzzi, Enzo; Nagaraj, Ram H; Shoham, Menachem; Kern, Timothy S; Medof, M Edward

    2018-01-01

    Decay accelerating factor (DAF or CD55) is a cell associated C3 and C5 convertase regulator originally described in terms of protection of self-cells from systemic complement but now known to modulate adaptive T cell responses. It is expressed on all cell types. We investigated whether nonenzymatic glycation could impair its function and potentially be relevant to complications of diabetes mellitus and other conditions that result in nonenzymatic glycation including cancer, Alzheimer's disease, and aging. Immunoblots of affinity-purified DAF from erythrocytes of patients with diabetes showed pentosidine, glyoxal-AGEs, carboxymethyllysine, and argpyrimidine. HPLC/MS analyses of glucose modified DAF localized the sites of AGE modifications to K 125 adjacent to K 126 , K 127 at the junction of CCPs2-3 and spatially near R 96 , and R 100 , all identified as being critical for DAF's function. Functional analyses of glucose or ribose treated DAF protein showed profound loss of its regulatory activity. The data argue that de-regulated activation of systemic complement and de-regulated activation of T cells and leukocytes could result from non-enzymatic glycation of DAF. Copyright © 2017. Published by Elsevier Ltd.

  18. Decay accelerating factor (DAF) is anchored to membranes by a C-terminal glycolipid

    International Nuclear Information System (INIS)

    Medof, M.E.; Haas, R.; Walter, E.I.; Rosenberry, T.L.

    1986-01-01

    Purified 70 kDa membrane (m) DAF incorporates into cells when added in vitro. A 2 kDa smaller DAF form which functions extrinsically like C4bp but is unable to incorporate can be isolated from urine (u). Because of common deficits of mDAF and acetylcholinesterase (AChE) in erythrocytes (E) of patients with paroxysmal nocturnal hemoglobinuria (PNH), mDAF was analyzed for a O-terminal glycolipid membrane anchor similar to that in E AChE. Incubation of E with phosphatidylinositol-specific phospholipase C, an enzyme which cleaves a similar glycolipid anchor in trypanosome variant surface glycoproteins (mfVSGs), released 20% of the DAF antigen. The released DAF species resembled uDAF in size, extrinsic model of C4b2a decay, and lack of hydrophobicity. Reductive radiomethylation of mDAF with [ 14 C]HCHO and NaCNBH 3 revealed ethanolamine and glucosamine in proportions similar to those in the E AChE glycolipid anchor. Papain cleavage of radiomethylated mDAF released the labeled ethanolamine and glucosamine in small O-terminal fragments from the residual DAF that retained N-terminal Asp. Following labeling of the anchors of mDAF and E AChE with the lipophilic photoreagent 3-trifluoromethyl-3-(m-[ 125 I]iodophenyl)diazirine, cleavage at the glucosamine residue by deamination quantitatively released the label from both proteins. Biosynthetic labeling of Hela cells with [ 3 H]ethanolamine resulted in rapid 3 H incorporation into both 48 kDa proDAF and 70 kDa mDAF. These data indicate that mDAF is anchored by a glycolipid similar to that in E AChE, mfVSGs and Thy-1 antigen and raise the possibility that a defect in the assembly or attachment of this structure could account for the deficits of mDAF and E AChE in PNH

  19. Interaction of hookworm 14-3-3 with the forkhead transcription factor DAF-16 requires intact Akt phosphorylation sites

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    Hawdon John M

    2009-04-01

    Full Text Available Abstract Background Third-stage infective larvae (L3 of hookworms are in an obligatory state of developmental arrest that ends upon entering the definitive host, where they receive a signal that re-activates development. Recovery from the developmentally arrested dauer stage of Caenorhabditis elegans is analogous to the resumption of development during hookworm infection. Insulin-like signaling (ILS mediates recovery from arrest in C. elegans and activation of hookworm dauer L3. In C. elegans, phosphorylation of the forkhead transcription factor DAF-16 in response to ILS creates binding cites for the 14-3-3 protein Ce-FTT-2, which translocates DAF-16 out of the nucleus, resulting in resumption of reproductive development. Results To determine if hookworm 14-3-3 proteins play a similar role in L3 activation, hookworm FTT-2 was identified and tested for its ability to interact with A. caninum DAF-16 in vitro. The Ac-FTT-2 amino acid sequence was 91% identical to the Ce-FTT-2, and was most closely related to FTT-2 from other nematodes. Ac-FTT-2 was expressed in HEK 293T cells, and was recognized by an antibody against human 14-3-3β isoform. Reciprocal co-immunoprecipitations using anti-epitope tag antibodies indicated that Ac-FTT-2 interacts with Ac-DAF-16 when co-expressed in serum-stimulated HEK 293T cells. This interaction requires intact Akt consensus phosphorylation sites at serine107 and threonine312, but not serine381. Ac-FTT-2 was undetectable by Western blot in excretory/secretory products from serum-stimulated (activated L3 or adult A. caninum. Conclusion The results indicate that Ac-FTT-2 interacts with DAF-16 in a phosphorylation-site dependent manner, and suggests that Ac-FTT-2 mediates activation of L3 by binding Ac-DAF-16 during hookworm infection.

  20. DAF as a therapeutic target for steroid hormones: implications for host-pathogen interactions.

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    Nowicki, Bogdan; Nowicki, Stella

    2013-01-01

    In this chapter, we present a concise historic prospective and a summary of accumulated knowledge on steroid hormones, DAF expression, and therapeutic implication of steroid hormone treatment on multiple pathologies, including infection and the host-pathogen interactions. DAF/CD55 plays multiple physiologic functions including tissue protection from the cytotoxic complement injury, an anti-inflammatory function due to its anti-adherence properties which enhance transmigration of monocytes and macrophages and reduce tissue injury. DAF physiologic functions are essential in many organ systems including pregnancy for protection of the semiallogeneic fetus or for preventing uncontrolled infiltration by white cells in their pro- and/or anti-inflammatory functions. DAF expression appears to have multiple regulatory tissue-specific and/or menstrual cycle-specific mechanisms, which involve complex signaling mechanisms. Regulation of DAF expression may involve a direct or an indirect effect of at least the estrogen, progesterone, and corticosteroid regulatory pathways. DAF is exploited in multiple pathologic conditions by pathogens and viruses in chronic tissue infection processes. The binding of Escherichia coli bearing Dr adhesins to the DAF/CD55 receptor is DAF density dependent and triggers internalization of E. coli via an endocytic pathway involving CD55, lipid rafts, and microtubules. Dr+ E. coli or Dr antigen may persist in vivo in the interstitium for several months. Further understanding of such processes should be instrumental in designing therapeutic strategies for multiple conditions involving DAF's protective or pathologic functions and tailoring host expression of DAF.

  1. The in vitro protection of human decay accelerating factor and hDAF/heme oxygenase-1 transgenes in porcine aortic endothelial cells against sera of Formosan macaques.

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    Tu, C-F; Tai, H-C; Wu, C-P; Ho, L-L; Lin, Y-J; Hwang, C-S; Yang, T-S; Lee, J-M; Tseng, Y-L; Huang, C-C; Weng, C-N; Lee, P-H

    2010-01-01

    To mitigate hyperacute rejection, pigs have been generated with alpha-Gal transferase gene knockout and transgenic expression of human decay accelerating factor (hDAF), MCP, and CD59. Additionally, heme-oxygenase-1 (HO-1) has been suggested to defend endothelial cells. Sera (MS) (0%, 1%, 5%, 10%, and 15%) from Formosan macaques (Macaca cyclopis, MC), an Old World monkey wildly populated in Taiwan, was used to test the protective in vitro, effects of hDAF or hDAF/hHO-1 on porcine aortic endothelial cells (pAEC) derived from hDAF(+), hDAF(+)/hHO-1(+), and hDAF(+)/hHO-1(-) and 1 nontransgenic pAEC. Ten percent human serum (HS) served as a positive control. When MS addition increased to 10% or 15%, all transgenic pAEC exhibited a greater survival than nontransgenic pAEC. Noticeably, 15% MS reduced survived to 40% in nontransgenic and transgenic pAEC, respectively. These results revealed that hDAF exerted protective effects against MC complement activation. However, comparing with 10% MS and HS in pAEC of nontransgenic pigs, the survivability was higher in HS, suggesting that complement activation by MS was more toxic than that by HS. Furthermore, hDAF(+)/hHO-1(+) showed no further protection against effects of MS on transgenic pAEC. Copyright 2010 Elsevier Inc. All rights reserved.

  2. CD55 deposited on synovial collagen fibers protects from immune complex-mediated arthritis

    NARCIS (Netherlands)

    Karpus, Olga N.; Kiener, Hans P.; Niederreiter, Birgit; Yilmaz-Elis, A. Seda; van der Kaa, Jos; Ramaglia, Valeria; Arens, Ramon; Smolen, Josef S.; Botto, Marina; Tak, Paul P.; Verbeek, J. Sjef; Hamann, Jörg

    2015-01-01

    CD55, a glycosylphosphatidylinositol-anchored, complement-regulating protein (decay-accelerating factor), is expressed by fibroblast-like synoviocytes (FLS) with high local abundance in the intimal lining layer. We here explored the basis and consequences of this uncommon presence. Synovial tissue,

  3. RFX Transcription Factor DAF-19 Regulates 5-HT and Innate Immune Responses to Pathogenic Bacteria in Caenorhabditis elegans

    Science.gov (United States)

    Choi, Sunju; Xu, Lu; Sze, Ji Ying

    2013-01-01

    In Caenorhabditis elegans the Toll-interleukin receptor domain adaptor protein TIR-1 via a conserved mitogen-activated protein kinase (MAPK) signaling cascade induces innate immunity and upregulates serotonin (5-HT) biosynthesis gene tph-1 in a pair of ADF chemosensory neurons in response to infection. Here, we identify transcription factors downstream of the TIR-1 signaling pathway. We show that common transcription factors control the innate immunity and 5-HT biosynthesis. We demonstrate that a cysteine to tyrosine substitution in an ARM motif of the HEAT/Arm repeat region of the TIR-1 protein confers TIR-1 hyperactivation, leading to constitutive tph-1 upregulation in the ADF neurons, increased expression of intestinal antimicrobial genes, and enhanced resistance to killing by the human opportunistic pathogen Pseudomonas aeruginosa PA14. A forward genetic screen for suppressors of the hyperactive TIR-1 led to the identification of DAF-19, an ortholog of regulatory factor X (RFX) transcription factors that are required for human adaptive immunity. We show that DAF-19 concerts with ATF-7, a member of the activating transcription factor (ATF)/cAMP response element-binding B (CREB) family of transcription factors, to regulate tph-1 and antimicrobial genes, reminiscent of RFX-CREB interaction in human immune cells. daf-19 mutants display heightened susceptibility to killing by PA14. Remarkably, whereas the TIR-1-MAPK-DAF-19/ATF-7 pathway in the intestinal immunity is regulated by DKF-2/protein kinase D, we found that the regulation of tph-1 expression is independent of DKF-2 but requires UNC-43/Ca2+/calmodulin-dependent protein kinase (CaMK) II. Our results suggest that pathogenic cues trigger a common core-signaling pathway via tissue-specific mechanisms and demonstrate a novel role for RFX factors in neuronal and innate immune responses to infection. PMID:23505381

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

    Science.gov (United States)

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

    2017-08-09

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

  5. RNA helicase HEL-1 promotes longevity by specifically activating DAF-16/FOXO transcription factor signaling in Caenorhabditis elegans

    Science.gov (United States)

    Seo, Mihwa; Seo, Keunhee; Hwang, Wooseon; Koo, Hee Jung; Hahm, Jeong-Hoon; Yang, Jae-Seong; Han, Seong Kyu; Hwang, Daehee; Kim, Sanguk; Jang, Sung Key; Lee, Yoontae; Nam, Hong Gil; Lee, Seung-Jae V.

    2015-01-01

    The homeostatic maintenance of the genomic DNA is crucial for regulating aging processes. However, the role of RNA homeostasis in aging processes remains unknown. RNA helicases are a large family of enzymes that regulate the biogenesis and homeostasis of RNA. However, the functional significance of RNA helicases in aging has not been explored. Here, we report that a large fraction of RNA helicases regulate the lifespan of Caenorhabditis elegans. In particular, we show that a DEAD-box RNA helicase, helicase 1 (HEL-1), promotes longevity by specifically activating the DAF-16/forkhead box O (FOXO) transcription factor signaling pathway. We find that HEL-1 is required for the longevity conferred by reduced insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) and is sufficient for extending lifespan. We further show that the expression of HEL-1 in the intestine and neurons contributes to longevity. HEL-1 enhances the induction of a large fraction of DAF-16 target genes. Thus, the RNA helicase HEL-1 appears to promote longevity in response to decreased IIS as a transcription coregulator of DAF-16. Because HEL-1 and IIS are evolutionarily well conserved, a similar mechanism for longevity regulation via an RNA helicase-dependent regulation of FOXO signaling may operate in mammals, including humans. PMID:26195740

  6. Reversible reprotoxic effects of manganese through DAF-16 transcription factor activation and vitellogenin downregulation in Caenorhabditis elegans.

    Science.gov (United States)

    Gubert, Priscila; Puntel, Bruna; Lehmen, Tassia; Bornhorst, Julia; Avila, Daiana S; Aschner, Michael; Soares, Felix A A

    2016-04-15

    Vitellogenesis is the yolk production process which provides the essential nutrients for the developing embryos. Yolk is a lipoprotein particle that presents lipids and lipid-binding proteins, referred to as vitellogenins (VIT). The Caenorhabditis elegans nematode has six genes encoding VIT lipoproteins. Several pathways are known to regulate vitellogenesis, including the DAF-16 transcription factor. Some reports have shown that heavy metals, such as manganese (Mn), impair brood size in C. elegans; however the mechanisms associated with this effect have yet to be identified. Our aim was to evaluate Mn's effects on C. elegans reproduction and better understand the pathways related to these effects. Young adult larval stage worms were treated for 4h with Mn in 85mM NaCl and Escherichia coli OP50 medium. Mn reduced egg-production and egg-laying during the first 24h after the treatment, although the total number of progenies were indistinguishable from the control group levels. This delay may have occurred due to DAF-16 activation, which was noted only after the treatment and was not apparent 24h later. Moreover, the expression, protein levels and green fluorescent protein (GFP) fluorescence associated with VIT were decreased soon after Mn treatment and recovered after 24h. Combined, these data suggest that the delay in egg-production is likely regulated by DAF-16 and followed by the inhibition of VIT transport activity. Further studies are needed to clarify the mechanisms associated with Mn-induced DAF-16 activation. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Isoxanthohumol, a constituent of hop (Humulus lupulus L.), increases stress resistance in Caenorhabditis elegans dependent on the transcription factor DAF-16.

    Science.gov (United States)

    Büchter, Christian; Havermann, Susannah; Koch, Karoline; Wätjen, Wim

    2016-02-01

    The flavanone isoxanthohumol (IX) has gained attention as antioxidative and chemopreventive agent, but the molecular mechanism of action remains unclear. We investigated effects of this secondary plant compound in vivo using the model organism Caenorhabditis elegans. Adult C. elegans nematodes were incubated with IX, and then, the stress resistance was analysed in the SYTOX assay; lifespan was monitored by touch-provoked movement method, the amount of reactive oxygen species (ROS) was measured in the DCF assay, and the nuclear localisation of the transcription factor DAF-16 was analysed by using a transgenic strain. By the use of a DAF-16 loss-of-function strain, we analysed whether the effects are dependent on DAF-16. IX increases the resistance of the nematode against thermal stress. Additionally, a reduction in ROS in vivo was caused by IX. Since the flavanone only has a marginal radical-scavenging capacity (TEAC assay), we suggest that IX mediates its antioxidative effects indirectly via activation of DAF-16 (homologue to mammalian FOXO proteins). The nuclear translocation of this transcription factor is increased by IX. In the DAF-16-mutated strain, the IX-mediated increase in stress resistance was completely abolished; furthermore, an increased formation of ROS and a reduced lifespan was mediated by IX. IX or a bacterial metabolite of IX causes antioxidative effects as well as an increased stress resistance in C. elegans via activation of DAF-16. The homologous pathway may have implications in the molecular mechanism of IX in mammals.

  8. Deletion of Crry and DAF on murine platelets stimulates thrombopoiesis and increases factor H-dependent resistance of peripheral platelets to complement attack.

    Science.gov (United States)

    Barata, Lidia; Miwa, Takashi; Sato, Sayaka; Kim, David; Mohammed, Imran; Song, Wen-Chao

    2013-03-15

    Complement receptor 1-related gene/protein y (Crry) and decay-accelerating factor (DAF) are two murine membrane C3 complement regulators with overlapping functions. Crry deletion is embryonically lethal whereas DAF-deficient mice are generally healthy. Crry(-/-)DAF(-/-) mice were viable on a C3(-/-) background, but platelets from such mice were rapidly destroyed when transfused into C3-sufficient mice. In this study, we used the cre-lox system to delete platelet Crry in DAF(-/-) mice and studied Crry/DAF-deficient platelet development in vivo. Rather than displaying thrombocytopenia, Pf4-Cre(+)-Crry(flox/flox) mice had normal platelet counts and their peripheral platelets were resistant to complement attack. However, chimera mice generated with Pf4-Cre(+)-Crry(flox/flox) bone marrows showed platelets from C3(-/-) but not C3(+/+) recipients to be sensitive to complement activation, suggesting that circulating platelets in Pf4-Cre(+)-Crry(flox/flox) mice were naturally selected in a complement-sufficient environment. Notably, Pf4-Cre(+)-Crry(flox/flox) mouse platelets became complement susceptible when factor H function was blocked. Examination of Pf4-Cre(+)-Crry(flox/flox) mouse bone marrows revealed exceedingly active thrombopoiesis. Thus, under in vivo conditions, Crry/DAF deficiency on platelets led to abnormal platelet turnover, but peripheral platelet count was compensated for by increased thrombopoiesis. Selective survival of Crry/DAF-deficient platelets aided by factor H protection and compensatory thrombopoiesis demonstrates the cooperation between membrane and fluid phase complement inhibitors and the body's ability to adaptively respond to complement regulator deficiencies.

  9. The DAF-16 FOXO transcription factor regulates natc-1 to modulate stress resistance in Caenorhabditis elegans, linking insulin/IGF-1 signaling to protein N-terminal acetylation.

    Directory of Open Access Journals (Sweden)

    Kurt Warnhoff

    2014-10-01

    Full Text Available The insulin/IGF-1 signaling pathway plays a critical role in stress resistance and longevity, but the mechanisms are not fully characterized. To identify genes that mediate stress resistance, we screened for C. elegans mutants that can tolerate high levels of dietary zinc. We identified natc-1, which encodes an evolutionarily conserved subunit of the N-terminal acetyltransferase C (NAT complex. N-terminal acetylation is a widespread modification of eukaryotic proteins; however, relatively little is known about the biological functions of NATs. We demonstrated that loss-of-function mutations in natc-1 cause resistance to a broad-spectrum of physiologic stressors, including multiple metals, heat, and oxidation. The C. elegans FOXO transcription factor DAF-16 is a critical target of the insulin/IGF-1 signaling pathway that mediates stress resistance, and DAF-16 is predicted to directly bind the natc-1 promoter. To characterize the regulation of natc-1 by DAF-16 and the function of natc-1 in insulin/IGF-1 signaling, we analyzed molecular and genetic interactions with key components of the insulin/IGF-1 pathway. natc-1 mRNA levels were repressed by DAF-16 activity, indicating natc-1 is a physiological target of DAF-16. Genetic studies suggested that natc-1 functions downstream of daf-16 to mediate stress resistance and dauer formation. Based on these findings, we hypothesize that natc-1 is directly regulated by the DAF-16 transcription factor, and natc-1 is a physiologically significant effector of the insulin/IGF-1 signaling pathway that mediates stress resistance and dauer formation. These studies identify a novel biological function for natc-1 as a modulator of stress resistance and dauer formation and define a functionally significant downstream effector of the insulin/IGF-1 signaling pathway. Protein N-terminal acetylation mediated by the NatC complex may play an evolutionarily conserved role in regulating stress resistance.

  10. The DAF-16 FOXO transcription factor regulates natc-1 to modulate stress resistance in Caenorhabditis elegans, linking insulin/IGF-1 signaling to protein N-terminal acetylation.

    Science.gov (United States)

    Warnhoff, Kurt; Murphy, John T; Kumar, Sandeep; Schneider, Daniel L; Peterson, Michelle; Hsu, Simon; Guthrie, James; Robertson, J David; Kornfeld, Kerry

    2014-10-01

    The insulin/IGF-1 signaling pathway plays a critical role in stress resistance and longevity, but the mechanisms are not fully characterized. To identify genes that mediate stress resistance, we screened for C. elegans mutants that can tolerate high levels of dietary zinc. We identified natc-1, which encodes an evolutionarily conserved subunit of the N-terminal acetyltransferase C (NAT) complex. N-terminal acetylation is a widespread modification of eukaryotic proteins; however, relatively little is known about the biological functions of NATs. We demonstrated that loss-of-function mutations in natc-1 cause resistance to a broad-spectrum of physiologic stressors, including multiple metals, heat, and oxidation. The C. elegans FOXO transcription factor DAF-16 is a critical target of the insulin/IGF-1 signaling pathway that mediates stress resistance, and DAF-16 is predicted to directly bind the natc-1 promoter. To characterize the regulation of natc-1 by DAF-16 and the function of natc-1 in insulin/IGF-1 signaling, we analyzed molecular and genetic interactions with key components of the insulin/IGF-1 pathway. natc-1 mRNA levels were repressed by DAF-16 activity, indicating natc-1 is a physiological target of DAF-16. Genetic studies suggested that natc-1 functions downstream of daf-16 to mediate stress resistance and dauer formation. Based on these findings, we hypothesize that natc-1 is directly regulated by the DAF-16 transcription factor, and natc-1 is a physiologically significant effector of the insulin/IGF-1 signaling pathway that mediates stress resistance and dauer formation. These studies identify a novel biological function for natc-1 as a modulator of stress resistance and dauer formation and define a functionally significant downstream effector of the insulin/IGF-1 signaling pathway. Protein N-terminal acetylation mediated by the NatC complex may play an evolutionarily conserved role in regulating stress resistance.

  11. Triggering of the dsRNA sensors TLR3, MDA5, and RIG-I induces CD55 expression in synovial fibroblasts.

    Directory of Open Access Journals (Sweden)

    Olga N Karpus

    Full Text Available CD55 (decay-accelerating factor is a complement-regulatory protein highly expressed on fibroblast-like synoviocytes (FLS. CD55 is also a ligand for CD97, an adhesion-type G protein-coupled receptor abundantly present on leukocytes. Little is known regarding the regulation of CD55 expression in FLS.FLS isolated from arthritis patients were stimulated with pro-inflammatory cytokines and Toll-like receptor (TLR ligands. Transfection with polyinosinic-polycytidylic acid (poly(I:C and 5'-triphosphate RNA were used to activate the cytoplasmic double-stranded (dsRNA sensors melanoma differentiation-associated gene 5 (MDA5 and retinoic acid-inducible gene-I (RIG-I. CD55 expression, cell viability, and binding of CD97-loaded beads were quantified by flow cytometry.CD55 was expressed at equal levels on FLS isolated from patients with rheumatoid arthritis (RA, osteoarthritis, psoriatic arthritis and spondyloarthritis. CD55 expression in RA FLS was significantly induced by IL-1β and especially by the TLR3 ligand poly(I:C. Activation of MDA5 and RIG-I also enhanced CD55 expression. Notably, activation of MDA5 dose-dependently induced cell death, while triggering of TLR3 or RIG-I had a minor effect on viability. Upregulation of CD55 enhanced the binding capacity of FLS to CD97-loaded beads, which could be blocked by antibodies against CD55.Activation of dsRNA sensors enhances the expression of CD55 in cultured FLS, which increases the binding to CD97. Our findings suggest that dsRNA promotes the interaction between FLS and CD97-expressing leukocytes.

  12. Relative contributions of decay accelerating factor (DAF), membrane cofactor protein (MCP) and CD59 in the protection of melanocytes from homologous complement

    NARCIS (Netherlands)

    Venneker, G. T.; Vodegel, R. M.; Okada, N.; Westerhof, W.; Bos, J. D.; Asghar, S. S.

    1998-01-01

    Complement regulatory molecules, membrane cofactor protein (MCP), decay accelerating factor (DAF) and CD59, protect body cells from autologous complement. They have wide tissue distribution but nothing is known about the expression of these molecules on human melanocytes. Since melanocytes are lysed

  13. The Transcription Factor DAF-16 is Essential for Increased Longevity in C. elegans Exposed to Bifidobacterium longum BB68.

    Science.gov (United States)

    Zhao, Liang; Zhao, Yang; Liu, Ruihai; Zheng, Xiaonan; Zhang, Min; Guo, Huiyuan; Zhang, Hao; Ren, Fazheng

    2017-08-07

    The longevity-promoting benefits of lactobacilli were hypothesized as early as 1907. Although the anti-aging effects of lactic acid bacteria (LAB) have been observed in nematodes, rodents and humans for over a century, the mechanisms underlying the effects of probiotics on aging have rarely been assessed. Using the Caenorhabditis elegans (C. elegans) model, various studies have elucidated the role of different signaling cascades, especially the DAF-16 cascade, on lifespan extension by LAB. In this study, the mechanisms through which Bifidobacterium longum strain BB68 affects the longevity of C. elegans were assessed. The lifespan of nematodes increased by 28% after worms were fed BB68, and this extension of lifespan was completely lost in backgrounds containing a mutated DAF-16 gene. High levels of DAF-16 (in the daf-16 (mu86); muIs61 strain) nuclear accumulation and high expression of the SOD-3 gene (a DAF-16-specific target gene) were observed as a result of BB68 treatment. Immunofluorescence microscopy revealed that TIR-1 and JNK-1 are involved in the phosphorylation and activation of DAF-16. Thus, BB68 increased the longevity of nematodes by activating the TIR-1 - JNK-1 - DAF-16 signaling pathway, and the cell wall component of BB68 contributed to longevity.

  14. Regulation of Lysosomal Function by the DAF-16 Forkhead Transcription Factor Couples Reproduction to Aging in Caenorhabditis elegans.

    Science.gov (United States)

    Baxi, Kunal; Ghavidel, Ata; Waddell, Brandon; Harkness, Troy A; de Carvalho, Carlos E

    2017-09-01

    Aging in eukaryotes is accompanied by widespread deterioration of the somatic tissue. Yet, abolishing germ cells delays the age-dependent somatic decline in Caenorhabditis elegans In adult worms lacking germ cells, the activation of the DAF-9/DAF-12 steroid signaling pathway in the gonad recruits DAF-16 activity in the intestine to promote longevity-associated phenotypes. However, the impact of this pathway on the fitness of normally reproducing animals is less clear. Here, we explore the link between progeny production and somatic aging and identify the loss of lysosomal acidity-a critical regulator of the proteolytic output of these organelles-as a novel biomarker of aging in C. elegans The increase in lysosomal pH in older worms is not a passive consequence of aging, but instead is timed with the cessation of reproduction, and correlates with the reduction in proteostasis in early adult life. Our results further implicate the steroid signaling pathway and DAF-16 in dynamically regulating lysosomal pH in the intestine of wild-type worms in response to the reproductive cycle. In the intestine of reproducing worms, DAF-16 promotes acidic lysosomes by upregulating the expression of v-ATPase genes. These findings support a model in which protein clearance in the soma is linked to reproduction in the gonad via the active regulation of lysosomal acidification. Copyright © 2017 by the Genetics Society of America.

  15. A functional SNP in the regulatory region of the decay-accelerating factor gene associates with extraocular muscle pareses in myasthenia gravis

    KAUST Repository

    Heckmann, J M

    2009-08-13

    Complement activation in myasthenia gravis (MG) may damage muscle endplate and complement regulatory proteins such as decay-accelerating factor (DAF) or CD55 may be protective. We hypothesize that the increased prevalence of severe extraocular muscle (EOM) dysfunction among African MG subjects reported earlier may result from altered DAF expression. To test this hypothesis, we screened the DAF gene sequences relevant to the classical complement pathway and found an association between myasthenics with EOM paresis and the DAF regulatory region c.-198CG SNP (odds ratio8.6; P0.0003). This single nucleotide polymorphism (SNP) results in a twofold activation of a DAF 5?-flanking region luciferase reporter transfected into three different cell lines. Direct matching of the surrounding SNP sequence within the DAF regulatory region with the known transcription factor-binding sites suggests a loss of an Sp1-binding site. This was supported by the observation that the c.-198CG SNP did not show the normal lipopolysaccharide-induced DAF transcriptional upregulation in lymphoblasts from four patients. Our findings suggest that at critical periods during autoimmune MG, this SNP may result in inadequate DAF upregulation with consequent complement-mediated EOM damage. Susceptible individuals may benefit from anti-complement therapy in addition to immunosuppression. © 2010 Macmillan Publishers Limited. All rights reserved.

  16. Transgenic C. elegans dauer larvae expressing hookworm phospho null DAF-16/FoxO exit dauer.

    Directory of Open Access Journals (Sweden)

    Verena Gelmedin

    Full Text Available Parasitic hookworms and the free-living model nematode Caenorhabtidis elegans share a developmental arrested stage, called the dauer stage in C. elegans and the infective third-stage larva (L3 in hookworms. One of the key transcription factors that regulate entrance to and exit from developmental arrest is the forkhead transcription factor DAF-16/FoxO. During the dauer stage, DAF-16 is activated and localized in the nucleus. DAF-16 is negatively regulated by phosphorylation by the upstream kinase AKT, which causes DAF-16 to localize out of the nucleus and the worm to exit from dauer. DAF-16 is conserved in hookworms, and hypothesized to control recovery from L3 arrest during infection. Lacking reverse genetic techniques for use in hookworms, we used C. elegans complementation assays to investigate the function of Ancylostoma caninum DAF-16 during entrance and exit from L3 developmental arrest. We performed dauer switching assays and observed the restoration of the dauer phenotype when Ac-DAF-16 was expressed in temperature-sensitive dauer defective C. elegans daf-2(e1370;daf-16(mu86 mutants. AKT phosphorylation site mutants of Ac-DAF-16 were also able to restore the dauer phenotype, but surprisingly allowed dauer exit when temperatures were lowered. We used fluorescence microscopy to localize DAF-16 during dauer and exit from dauer in C. elegans DAF-16 mutant worms expressing Ac-DAF-16, and found that Ac-DAF-16 exited the nucleus during dauer exit. Surprisingly, Ac-DAF-16 with mutated AKT phosphorylation sites also exited the nucleus during dauer exit. Our results suggest that another mechanism may be involved in the regulation DAF-16 nuclear localization during recovery from developmental arrest.

  17. Lack of Association of CD55 Receptor Genetic Variants and Severe Malaria in Ghanaian Children

    Directory of Open Access Journals (Sweden)

    Kathrin Schuldt

    2017-03-01

    Full Text Available In a recent report, the cellular receptor CD55 was identified as a molecule essential for the invasion of human erythrocytes by Plasmodium falciparum, the causal agent of the most severe form of malaria. As this invasion process represents a critical step during infection with the parasite, it was hypothesized that genetic variants in the gene could affect severe malaria (SM susceptibility. We performed high-resolution variant discovery of rare and common genetic variants in the human CD55 gene. Association testing of these variants in over 1700 SM cases and unaffected control individuals from the malaria-endemic Ashanti Region in Ghana, West Africa, were performed on the basis of single variants, combined rare variant analyses, and reconstructed haplotypes. A total of 26 genetic variants were detected in coding and regulatory regions of CD55. Five variants were previously unknown. None of the single variants, rare variants, or haplotypes showed evidence for association with SM or P. falciparum density. Here, we present the first comprehensive analysis of variation in the CD55 gene in the context of SM and show that genetic variants present in a Ghanaian study group appear not to influence susceptibility to the disease.

  18. dbl-1/TGF-β and daf-12/NHR Signaling Mediate Cell-Nonautonomous Effects of daf-16/FOXO on Starvation-Induced Developmental Arrest.

    Directory of Open Access Journals (Sweden)

    Rebecca E W Kaplan

    2015-12-01

    Full Text Available Nutrient availability has profound influence on development. In the nematode C. elegans, nutrient availability governs post-embryonic development. L1-stage larvae remain in a state of developmental arrest after hatching until they feed. This "L1 arrest" (or "L1 diapause" is associated with increased stress resistance, supporting starvation survival. Loss of the transcription factor daf-16/FOXO, an effector of insulin/IGF signaling, results in arrest-defective and starvation-sensitive phenotypes. We show that daf-16/FOXO regulates L1 arrest cell-nonautonomously, suggesting that insulin/IGF signaling regulates at least one additional signaling pathway. We used mRNA-seq to identify candidate signaling molecules affected by daf-16/FOXO during L1 arrest. dbl-1/TGF-β, a ligand for the Sma/Mab pathway, daf-12/NHR and daf-36/oxygenase, an upstream component of the daf-12 steroid hormone signaling pathway, were up-regulated during L1 arrest in a daf-16/FOXO mutant. Using genetic epistasis analysis, we show that dbl-1/TGF-β and daf-12/NHR steroid hormone signaling pathways are required for the daf-16/FOXO arrest-defective phenotype, suggesting that daf-16/FOXO represses dbl-1/TGF-β, daf-12/NHR and daf-36/oxygenase. The dbl-1/TGF-β and daf-12/NHR pathways have not previously been shown to affect L1 development, but we found that disruption of these pathways delayed L1 development in fed larvae, consistent with these pathways promoting development in starved daf-16/FOXO mutants. Though the dbl-1/TGF-β and daf-12/NHR pathways are epistatic to daf-16/FOXO for the arrest-defective phenotype, disruption of these pathways does not suppress starvation sensitivity of daf-16/FOXO mutants. This observation uncouples starvation survival from developmental arrest, indicating that DAF-16/FOXO targets distinct effectors for each phenotype and revealing that inappropriate development during starvation does not cause the early demise of daf-16/FOXO mutants. Overall

  19. dbl-1/TGF-β and daf-12/NHR Signaling Mediate Cell-Nonautonomous Effects of daf-16/FOXO on Starvation-Induced Developmental Arrest.

    Science.gov (United States)

    Kaplan, Rebecca E W; Chen, Yutao; Moore, Brad T; Jordan, James M; Maxwell, Colin S; Schindler, Adam J; Baugh, L Ryan

    2015-12-01

    Nutrient availability has profound influence on development. In the nematode C. elegans, nutrient availability governs post-embryonic development. L1-stage larvae remain in a state of developmental arrest after hatching until they feed. This "L1 arrest" (or "L1 diapause") is associated with increased stress resistance, supporting starvation survival. Loss of the transcription factor daf-16/FOXO, an effector of insulin/IGF signaling, results in arrest-defective and starvation-sensitive phenotypes. We show that daf-16/FOXO regulates L1 arrest cell-nonautonomously, suggesting that insulin/IGF signaling regulates at least one additional signaling pathway. We used mRNA-seq to identify candidate signaling molecules affected by daf-16/FOXO during L1 arrest. dbl-1/TGF-β, a ligand for the Sma/Mab pathway, daf-12/NHR and daf-36/oxygenase, an upstream component of the daf-12 steroid hormone signaling pathway, were up-regulated during L1 arrest in a daf-16/FOXO mutant. Using genetic epistasis analysis, we show that dbl-1/TGF-β and daf-12/NHR steroid hormone signaling pathways are required for the daf-16/FOXO arrest-defective phenotype, suggesting that daf-16/FOXO represses dbl-1/TGF-β, daf-12/NHR and daf-36/oxygenase. The dbl-1/TGF-β and daf-12/NHR pathways have not previously been shown to affect L1 development, but we found that disruption of these pathways delayed L1 development in fed larvae, consistent with these pathways promoting development in starved daf-16/FOXO mutants. Though the dbl-1/TGF-β and daf-12/NHR pathways are epistatic to daf-16/FOXO for the arrest-defective phenotype, disruption of these pathways does not suppress starvation sensitivity of daf-16/FOXO mutants. This observation uncouples starvation survival from developmental arrest, indicating that DAF-16/FOXO targets distinct effectors for each phenotype and revealing that inappropriate development during starvation does not cause the early demise of daf-16/FOXO mutants. Overall, this study shows

  20. Antioxidative Activities of Both Oleic Acid and Camellia tenuifolia Seed Oil Are Regulated by the Transcription Factor DAF-16/FOXO in Caenorhabditis elegans.

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    Chia-Cheng Wei

    Full Text Available Tea seed oil is a high quality edible oil, yet lacking sufficient scientific evidences to support the nutritional and medical purposes. We identified major and minor components in Camellia tenuifolia seed oil and investigated the antioxidative activity and its underlying mechanisms in Caenorhabditis elegans.The results showed that the major constitutes in C. tenuifolia seed oil were unsaturated fatty acids (~78.4%. Moreover, two minor compounds, β-amyrin and β-sitosterol, were identified and their antioxidative activity was examined. We found that oleic acid was the major constitute in C. tenuifolia seed oil and plays a key role in the antioxidative activity of C. tenuifolia seed oil in C. elegans.This study found evidences that the transcription factor DAF-16/FOXO was involved in both oleic acid- and C. tenuifolia seed oil-mediated oxidative stress resistance in C. elegans. This study suggests the potential of C. tenuifolia seed oil as nutrient or functional foods.

  1. Data Analysis Facility (DAF)

    Science.gov (United States)

    1991-01-01

    NASA-Dryden's Data Analysis Facility (DAF) provides a variety of support services to the entire Dryden community. It provides state-of-the-art hardware and software systems, available to any Dryden engineer for pre- and post-flight data processing and analysis, plus supporting all archival and general computer use. The Flight Data Access System (FDAS) is one of the advanced computer systems in the DAF, providing for fast engineering unit conversion and archival processing of flight data delivered from the Western Aeronautical Test Range. Engineering unit conversion and archival formatting of flight data is performed by the DRACO program on a Sun 690MP and an E-5000 computer. Time history files produced by DRACO are then moved to a permanent magneto-optical archive, where they are network-accessible 24 hours a day, 7 days a week. Pertinent information about the individual flights is maintained in a relational (Sybase) database. The DAF also houses all general computer services, including; the Compute Server 1 and 2 (CS1 and CS2), the server for the World Wide Web, overall computer operations support, courier service, a CD-ROM Writer system, a Technical Support Center, the NASA Dryden Phone System (NDPS), and Hardware Maintenance.

  2. [The significances of peripheral neutrophils CD(55) and myeloperoxidase expression in patients with myeloperoxidase-specific anti-neutrophil cytoplasmic antibody associated vasculitis].

    Science.gov (United States)

    Zhou, X L; Zheng, M J; Shuai, Z W; Zhang, L; Zhang, M M; Chen, S Y

    2017-06-01

    Objective: To investigate the expression of CD(55) and myeloperoxidase (MPO) on neutrophils in patients with MPO-specific anti-neutrophil cytoplasmic antibody associated vasculitis(MPO-AAV), and analyze the relationship between the expression and clinical manifestation. Methods: Forty untreated patients with active MPO-AAV (patient group) and 30 healthy volunteers (control group) were enrolled in this study. The CD(55) on neutrophils and both membrane and cytoplasmic MPO were detected by flow cytometry. Serum fragment-from the activated complement factor B(Ba) and MPO were measured by ELISA. The clinical activity of vasculitis was valued by Birmingham vasculitis activity score-version 3(BVAS-V3). The significance of laboratory data was evaluated by Spearman correlation test and multivariate linear regression analysis. Results: (1)The mean fluorescence intensity(MFI) of CD(55) expressed on neutrophils was significantly higher than that in control group[4 068.6±2 306.0 vs 2 999.5±1 504.9, P =0.033]. Similar results of serum MPO and Ba in patient group were found compared to controls [500.0(381.0, 612.7) IU/L vs 286.9(225.5, 329.1) IU/L, P <0.001; 35.2(25.2, 79.5) ng/L vs 18.0(15.0, 28.0) ng/L, P <0.001], respectively. However, MIF of cytoplasmic MPO in patients was significantly lower than that of control group(1 577.1±1 175.9 vs 3 105.3±2 323.0, P =0.003) . (2) In patient group, cytoplasmic intensity of MPO was negatively associated with the serum levels of MPO( r =-0.710, P <0.001) and Ba ( r =-0.589, P =0.001). Moreover, serum MPO was positively associated with serum Ba( r =0.691, P <0.001). Membrane intensity of CD(55) on neutrophils was positively correlated with patient age ( r =0.514, P =0.001), C reactive protein ( r =0.376, P =0.018), peripheral neutrophils count ( r =0.485, P =0.001) and BVAS-V3 ( r =0.484, P =0.002), whereas negative correlation between membrane CD(55) and disease duration was seen ( r =-0.403, P =0.01). (3) The result of multiple

  3. PQM-1 complements DAF-16 as a key transcriptional regulator of DAF-2-mediated development and longevity.

    Science.gov (United States)

    Tepper, Ronald G; Ashraf, Jasmine; Kaletsky, Rachel; Kleemann, Gunnar; Murphy, Coleen T; Bussemaker, Harmen J

    2013-08-01

    Reduced insulin/IGF-1-like signaling (IIS) extends C. elegans lifespan by upregulating stress response (class I) and downregulating other (class II) genes through a mechanism that depends on the conserved transcription factor DAF-16/FOXO. By integrating genome-wide mRNA expression responsiveness to DAF-16 with genome-wide in vivo binding data for a compendium of transcription factors, we discovered that PQM-1 is the elusive transcriptional activator that directly controls development (class II) genes by binding to the DAF-16-associated element (DAE). DAF-16 directly regulates class I genes only, through the DAF-16-binding element (DBE). Loss of PQM-1 suppresses daf-2 longevity and further slows development. Surprisingly, the nuclear localization of PQM-1 and DAF-16 is controlled by IIS in opposite ways and was also found to be mutually antagonistic. We observe progressive loss of nuclear PQM-1 with age, explaining declining expression of PQM-1 targets. Together, our data suggest an elegant mechanism for balancing stress response and development. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. FoxO/Daf-16 restored thrashing movement reduced by heat stress in Caenorhabditis elegans.

    Science.gov (United States)

    Furuhashi, Tsubasa; Sakamoto, Kazuichi

    2014-04-01

    Many studies on thermotolerance have been done in Caenorhabditis elegans in order to extend survival under heat stress; Daf-16, a homolog of FoxO in C. elegans, was detected as the key factor in thermotolerance. However, the recovery process from heat stress damage has been seldom discussed. In this study, we analyzed the roles of FoxO/Daf-16 on the recovery from heat stress damage by monitoring thrashing movement. Heat shock reduced the movement, which was restored by culturing at 20°C. Thrashing movement was not restored in the daf-16 mutant, which suggests that Daf-16 is one of the essential factors in repairing the damage. Movement restoration was promoted in the daf-2 mutant, a homolog of insulin/IGF-1-like receptor, in a daf-16-dependent manner. In addition, heat stress decreased the expression of daf-28 and ins-7, agonists of Daf-2. Taken together, these results revealed that FoxO/Daf-16 removes heat stress damage and restores movement via inhibition of the insulin-like signaling pathway in C. elegans, suggesting that FoxO/Daf-16 plays a critical role in thermotolerance. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. The protein kinase MBK-1 contributes to lifespan extension in daf-2 mutant and germline-deficient Caenorhabditis elegans.

    Science.gov (United States)

    Mack, Hildegard I D; Zhang, Peichuan; Fonslow, Bryan R; Yates, John R

    2017-05-25

    In Caenorhabditis elegans , reduction of insulin/IGF-1 like signaling and loss of germline stem cells both increase lifespan by activating the conserved transcription factor DAF-16 (FOXO). While the mechanisms that regulate DAF-16 nuclear localization in response to insulin/IGF-1 like signaling are well characterized, the molecular pathways that act in parallel to regulate DAF-16 transcriptional activity, and the pathways that couple DAF-16 activity to germline status, are not fully understood at present. Here, we report that inactivation of MBK-1, the C. elegans ortholog of the human FOXO1-kinase DYRK1A substantially shortens the prolonged lifespan of daf-2 and glp-1 mutant animals while decreasing wild-type lifespan to a lesser extent. On the other hand, lifespan-reduction by mutation of the MBK-1-related kinase HPK-1 was not preferential for long-lived mutants. Interestingly, mbk-1 loss still allowed for DAF-16 nuclear accumulation but reduced expression of certain DAF-16 target genes in germline-less, but not in daf-2 mutant animals. These findings indicate that mbk-1 and daf-16 functionally interact in the germline- but not in the daf-2 pathway. Together, our data suggest mbk-1 as a novel regulator of C. elegans longevity upon both, germline ablation and DAF-2 inhibition, and provide evidence for mbk-1 regulating DAF-16 activity in germline-deficient animals.

  6. DAF-16: FOXO in the Context of C. elegans.

    Science.gov (United States)

    Tissenbaum, Heidi A

    2018-01-01

    In Caenorhabditis elegans, there is a single FOXO transcription factor homolog, encoded by the gene, daf-16. As a central regulator for multiple signaling pathways, DAF-16 integrates these signals which results in modulation of several biological processes including longevity, development, fat storage, stress resistance, innate immunity, and reproduction. Using C. elegans allows for studies of FOXO in the context of the whole animal. Therefore, manipulating levels or the activity of daf-16 results in phenotypic changes. Genetic and molecular analysis revealed that similar to other systems, DAF-16 is the downstream target of the conserved insulin/IGF-1 signaling (IIS) pathway; a PI 3-kinase/AKT signaling cascade that ultimately controls the regulation of DAF-16 nuclear localization. In this chapter, I will focus on understanding how a single gene daf-16 can incorporate signals from multiple upstream pathways and in turn modulate different phenotypes as well as the study of FOXO in the context of a whole organism. © 2018 Elsevier Inc. All rights reserved.

  7. Daf-2, Daf-16 and Daf-23: Genetically Interacting Genes Controlling Dauer Formation in Caenorhabditis Elegans

    OpenAIRE

    Gottlieb, S.; Ruvkun, G.

    1994-01-01

    Under conditions of high population density and low food, Caenorhabditis elegans forms an alternative third larval stage, called the dauer stage, which is resistant to desiccation and harsh environments. Genetic analysis of some dauer constitutive (Daf-c) and dauer defective (Daf-d) mutants has revealed a complex pathway that is likely to function in particular neurons and/or responding tissues. Here we analyze the genetic interactions between three genes which comprise a branch of the dauer ...

  8. Difference in Ulex europaeus agglutinin I-binding activity of decay-accelerating factor detected in the stools of patients with colorectal cancer and ulcerative colitis.

    Science.gov (United States)

    Okazaki, Hiroaki; Mizuno, Motowo; Nasu, Junichirou; Makidono, Chiho; Hiraoka, Sakiko; Yamamoto, Kazuhide; Okada, Hiroyuki; Fujita, Teizo; Tsuji, Takao; Shiratori, Yasushi

    2004-03-01

    Expression of decay-accelerating factor (DAF, CD55), a complement-regulatory glycoprotein, is enhanced in colorectal-cancer (CC) cells and colonic epithelium in ulcerative colitis (UC), and stools from these patients contain increased amounts of DAF. Carbohydrate chains of glycoproteins are often altered during malignant transformation or inflammation. In this study, we investigated whether DAF molecules in patients with CC and those with UC differ with respect to oligosaccharide side chains. We analyzed DAF in stools and homogenates of colonic-tissue specimens obtained from patients with CC or UC using solid-phase enzyme-linked assay and Western blotting for reactivity with the lectins Ulex europaeus agglutinin I (UEA-I), wheat-germ agglutinin, peanut agglutinin, and concanavalin A. UEA-I bound to DAF in stools from patients with UC but not in that from the stools of CC patients, as demonstrated on the solid-phase enzyme-linked assay (P <.05, Mann-Whitney U test) and Western blotting. Binding of UEA-I was specifically inhibited by the addition of fucose. The difference in UEA-I reactivity with DAF was observed also in colonic-tissue homogenates from patients with UC and those with CC. DAF expressed in the mucosa and excreted into the stools of UC patients is different from that expressed in CC with regard to UEA-I reactivity. Future studies should be directed toward determining whether a qualitatively unique isoform of DAF is present, of which sugar chains are specific to CC in UC patients.

  9. The DAF-7/TGF-β signaling pathway regulates abundance of the C. elegans glutamate receptor GLR-1

    Science.gov (United States)

    McGehee, Annette M.; Moss, Benjamin J.; Juo, Peter

    2015-01-01

    Transforming growth factor-β (TGF-β) family signaling pathways have roles in both neuronal development and the regulation of synaptic function. Here we identify a novel role for the C. elegans DAF-7/TGF-β signaling pathway in the regulation of the AMPA-type glutamate receptor GLR-1. We found that the abundance of GLR-1 increases at synapses in the ventral nerve cord (VNC) of animals with loss-of-function mutations in multiple DAF-7/TGF-β pathway components including the TGF-β ligand DAF-7, the type I receptor DAF-1, and the Smads DAF-8 and DAF-14. The GLR-1 defect can be rescued by expression of daf-8 specifically in glr-1-expressing interneurons. The effect on GLR-1 was specific for the DAF-7 pathway because mutations in the DBL-1/TGF-β family pathway did not increase GLR-1 levels in the VNC. Immunoblot analysis indicates that total levels of GLR-1 protein are increased in neurons of DAF-7/TGF-β pathway mutants. The increased abundance of GLR-1 in the VNC of daf-7 pathway mutants is dependent on the transcriptional regulator DAF-3/Smad suggesting that DAF-3-dependent transcription controls GLR-1 levels. Furthermore, we found that glr-1 transcription is increased in daf-7 mutants based on a glr-1 transcriptional reporter. Together these results suggest that the DAF-7/TGF-β signaling pathway functions in neurons and negatively regulates the abundance of GLR-1, in part, by controlling transcription of the receptor itself. Finally, DAF-7/TGF-β pathway mutants exhibit changes in spontaneous locomotion that are dependent on endogenous GLR-1 and consistent with increased glutamatergic signaling. These results reveal a novel mechanism by which TGF-β signaling functions in the nervous system to regulate behavior. PMID:26054666

  10. The DAF-7/TGF-β signaling pathway regulates abundance of the Caenorhabditis elegans glutamate receptor GLR-1.

    Science.gov (United States)

    McGehee, Annette M; Moss, Benjamin J; Juo, Peter

    2015-07-01

    Transforming growth factor-β (TGF-β) family signaling pathways have roles in both neuronal development and the regulation of synaptic function. Here we identify a novel role for the Caenorhabditis elegans DAF-7/TGF-β signaling pathway in the regulation of the AMPA-type glutamate receptor GLR-1. We found that the abundance of GLR-1 increases at synapses in the ventral nerve cord (VNC) of animals with loss-of-function mutations in multiple DAF-7/TGF-β pathway components including the TGF-β ligand DAF-7, the type I receptor DAF-1, and the Smads DAF-8 and DAF-14. The GLR-1 defect can be rescued by expression of daf-8 specifically in glr-1-expressing interneurons. The effect on GLR-1 was specific for the DAF-7 pathway because mutations in the DBL-1/TGF-β family pathway did not increase GLR-1 levels in the VNC. Immunoblot analysis indicates that total levels of GLR-1 protein are increased in neurons of DAF-7/TGF-β pathway mutants. The increased abundance of GLR-1 in the VNC of daf-7 pathway mutants is dependent on the transcriptional regulator DAF-3/Smad suggesting that DAF-3-dependent transcription controls GLR-1 levels. Furthermore, we found that glr-1 transcription is increased in daf-7 mutants based on a glr-1 transcriptional reporter. Together these results suggest that the DAF-7/TGF-β signaling pathway functions in neurons and negatively regulates the abundance of GLR-1, in part, by controlling transcription of the receptor itself. Finally, DAF-7/TGF-β pathway mutants exhibit changes in spontaneous locomotion that are dependent on endogenous GLR-1 and consistent with increased glutamatergic signaling. These results reveal a novel mechanism by which TGF-β signaling functions in the nervous system to regulate behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Transcriptional regulation of Caenorhabditis elegans FOXO/DAF-16 modulates lifespan.

    Science.gov (United States)

    Bansal, Ankita; Kwon, Eun-Soo; Conte, Darryl; Liu, Haibo; Gilchrist, Michael J; MacNeil, Lesley T; Tissenbaum, Heidi A

    2014-01-01

    Insulin/IGF-1 signaling plays a central role in longevity across phylogeny. In C. elegans, the forkhead box O (FOXO) transcription factor, DAF-16, is the primary target of insulin/IGF-1 signaling, and multiple isoforms of DAF-16 (a, b, and d/f) modulate lifespan, metabolism, dauer formation, and stress resistance. Thus far, across phylogeny modulation of mammalian FOXOs and DAF-16 have focused on post-translational regulation with little focus on transcriptional regulation. In C. elegans, we have previously shown that DAF-16d/f cooperates with DAF-16a to promote longevity. In this study, we generated transgenic strains expressing near-endogenous levels of either daf-16a or daf-16d/f, and examined temporal expression of the isoforms to further define how these isoforms contribute to lifespan regulation. Here, we show that DAF-16a is sensitive both to changes in gene dosage and to alterations in the level of insulin/IGF-1 signaling. Interestingly, we find that as worms age, the intestinal expression of daf-16d/f but not daf-16a is dramatically upregulated at the level of transcription. Preventing this transcriptional upregulation shortens lifespan, indicating that transcriptional regulation of daf-16d/f promotes longevity. In an RNAi screen of transcriptional regulators, we identify elt-2 (GATA transcription factor) and swsn-1 (core subunit of SWI/SNF complex) as key modulators of daf-16d/f gene expression. ELT-2 and another GATA factor, ELT-4, promote longevity via both DAF-16a and DAF-16d/f while the components of SWI/SNF complex promote longevity specifically via DAF-16d/f. Our findings indicate that transcriptional control of C. elegans FOXO/daf-16 is an essential regulatory event. Considering the conservation of FOXO across species, our findings identify a new layer of FOXO regulation as a potential determinant of mammalian longevity and age-related diseases such as cancer and diabetes.

  12. DAF-fluorescence without NO: elicitor treated tobacco cells produce fluorescing DAF-derivatives not related to DAF-2 triazol.

    Science.gov (United States)

    Rümer, Stefan; Krischke, Markus; Fekete, Agnes; Mueller, Martin J; Kaiser, Werner M

    2012-08-15

    Diaminofluorescein-dyes (DAFs) are widely used for visualizing NO· production in biological systems. Here it was examined whether DAF-fluorescence could be evoked by other means than nitrosation. Tobacco (Nicotiana tabacum) suspension cells treated with the fungal elicitor cryptogein released compound(s) which gave a fluorescence increase in the cell-free filtrate after addition of DAF-2 or DAF-FM or DAR-4M. DAF-reactive compounds were relatively stable and identified as reaction products of H(2)O(2) plus apoplastic peroxidase (PO). CPTIO prevented formation of these products. Horseradish-peroxidase (HR-PO) plus H(2)O(2) also generated DAF-fluorescence in vitro. Using RP-HPLC with fluorescence detection, DAF derivatives were further analyzed. In filtrates from cryptogein-treated cells, fluorescence originated from two novel DAF-derivatives also obtained in vitro with DAF-2+HR-PO+H(2)O(2). DAF-2T was only detected when an NO donor (DEA-NO) was present. Using high resolution mass spectrometry, the two above-described novel DAF-reaction products were tentatively identified as dimers. In cells preloaded with DAF-2 DA and incubated with or without cryptogein, DAF-fluorescence originated from a complex pattern of multiple products different from those obtained in vitro. One specific peak was responsive to exogenous H(2)O(2), and another, minor peak eluted at or close to DAF-2T. Thus, in contrast to the prevailing opinion, DAF-2 can be enzymatically converted into a variety of highly fluorescing derivatives, both inside and outside cells, of which none (outside) or only a minor part (inside) appeared NO· dependent. Accordingly, DAF-fluorescence and its prevention by cPTIO do not necessarily indicate NO· production. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Caenorhabditis elegans DAF-16/FOXO Transcription Factor and Its Mammalian Homologs Associate with Age-Related Disease

    NARCIS (Netherlands)

    Hesp, K.; Smant, G.; Kammenga, J.E.

    2015-01-01

    The insulin/IGF-1 signaling pathway is evolutionarily conserved and its function is mediated largely by FOXO transcription factors. Reduced insulin/IGF-1 signaling leads to translocation of FOXO proteins from the cytoplasm to the nucleus where they activate a set of genes that mediate oxidative

  14. Structural and functional characterisation of FOXO/Acan-DAF-16 from the parasitic nematode Angiostrongylus cantonensis.

    Science.gov (United States)

    Yan, Baolong; Sun, Weiwei; Yan, Lanzhu; Zhang, Liangliang; Zheng, Yuan; Zeng, Yuzhen; Huang, Huicong; Liang, Shaohui

    2016-12-01

    Fork head box transcription factors subfamily O (FoxO) is regarded to be significant in cell-cycle control, cell differentiation, ageing, stress response, apoptosis, tumour formation and DNA damage repair. In the free-living nematode Caenorhabditis elegans, the FoxO transcription factor is encoded by Ce-daf-16, which is negatively regulated by insulin-like signaling (IIS) and involved in promoting dauer formation through bringing about its hundreds of downstream genes expression. In nematode parasites, orthologues of daf-16 from several species have been identified, with functions in rescue of dauer phenotypes determined in a surrogate system C. elegans. In this study, we identified the FoxO encoding gene, Acan-daf-16, from the parasitic nematode Angiostrongylus cantonensis, and determined the genomic structures, transcripts and functions far more thorough in longevity, stress resistance and dauer formation. Acan-daf-16 encodes two proteins, Acan-DAF-16A and Acan-DAF-16B, consisting of 555 and 491 amino acids, respectively. Both isoforms possess the highly conserved fork head domains. Acan-daf-16A and Acan-daf-16B are expressed from distinct promoters. The expression patterns of Acan-daf-16 isoforms in the C. elegans surrogate system showed that p Acan-daf-16a:gfp was expressed in all cells of C. elegans, including the pharynx, and the expression of p Acan-daf-16b:gfp was restricted to the pharynx. In addition to the same genomic organization to the orthologue in C. elegans, Ce-daf-16, both Acan-DAF-16 isoforms could restore the C. elegans daf-16(mg54) mutation in longevity, dauer formation and stress resistance, in spite of the partial complementation of Acan-DAF-16B isoform in longevity. These findings provide further evidence of the functional conservation of DAF-16s between parasitic nematodes and the free-living nematode C. elegans. Copyright © 2016. Published by Elsevier B.V.

  15. DAF-16 employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity.

    Science.gov (United States)

    Riedel, Christian G; Dowen, Robert H; Lourenco, Guinevere F; Kirienko, Natalia V; Heimbucher, Thomas; West, Jason A; Bowman, Sarah K; Kingston, Robert E; Dillin, Andrew; Asara, John M; Ruvkun, Gary

    2013-05-01

    Organisms are constantly challenged by stresses and privations and require adaptive responses for their survival. The forkhead box O (FOXO) transcription factor DAF-16 (hereafter referred to as DAF-16/FOXO) is a central nexus in these responses, but despite its importance little is known about how it regulates its target genes. Proteomic identification of DAF-16/FOXO-binding partners in Caenorhabditis elegans and their subsequent functional evaluation by RNA interference revealed several candidate DAF-16/FOXO cofactors, most notably the chromatin remodeller SWI/SNF. DAF-16/FOXO and SWI/SNF form a complex and globally co-localize at DAF-16/FOXO target promoters. We show that specifically for gene activation, DAF-16/FOXO depends on SWI/SNF, facilitating SWI/SNF recruitment to target promoters, to activate transcription by presumed remodelling of local chromatin. For the animal, this translates into an essential role for SWI/SNF in DAF-16/FOXO-mediated processes, in particular dauer formation, stress resistance and the promotion of longevity. Thus, we give insight into the mechanisms of DAF-16/FOXO-mediated transcriptional regulation and establish a critical link between ATP-dependent chromatin remodelling and lifespan regulation.

  16. L1 arrest, daf-16/FoxO and nonautonomous control of post-embryonic development.

    Science.gov (United States)

    Kaplan, Rebecca E W; Baugh, L Ryan

    2016-01-01

    Post-embryonic development is governed by nutrient availability. L1 arrest, dauer formation and aging illustrate how starvation, anticipation of starvation and caloric restriction have profound influence on C. elegans development, respectively. Insulin-like signaling through the Forkhead box O transcription factor daf-16/FoxO regulates each of these processes. We recently reported that ins-4, ins-6 and daf-28 promote L1 development from the intestine and chemosensory neurons, similar to their role in dauer development. daf-16 functions cell-nonautonomously in regulation of L1 arrest, dauer development and aging. Discrepancies in daf-16 sites of action have been reported in each context, but the consensus implicates epidermis, intestine and nervous system. We suggest technical limitations of the experimental approach responsible for discrepant results. Steroid hormone signaling through daf-12/NHR is known to function downstream of daf-16 in control of dauer development, but signaling pathways mediating cell-nonautonomous effects of daf-16 in aging and L1 arrest had not been identified. We recently showed that daf-16 promotes L1 arrest by inhibiting daf-12/NHR and dbl-1/TGF-β Sma/Mab signaling, two pathways that promote L1 development in fed larvae. We will review these results on L1 arrest and speculate on why there are so many signals and signaling centers regulating post-embryonic development.

  17. DAF-16 employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity

    NARCIS (Netherlands)

    Riedel, Christian G; Dowen, Robert H; Lourenco, Guinevere F; Kirienko, Natalia V; Heimbucher, Thomas; West, Jason A; Bowman, Sarah K; Kingston, Robert E; Dillin, Andrew; Asara, John M; Ruvkun, Gary

    Organisms are constantly challenged by stresses and privations and require adaptive responses for their survival. The forkhead box O (FOXO) transcription factor DAF-16 (hereafter referred to as DAF-16/FOXO) is a central nexus in these responses, but despite its importance little is known about how

  18. Dansk Almenmedicinsk Forskningsdag - DAF 2013

    DEFF Research Database (Denmark)

    Jensen, Jacob Reinholdt; Ryborg, Christina Trankjær; Smidth, Margrethe

    2013-01-01

    Ideen om DAF udsprang på en indisk restaurant for to år siden, da repræsentanter fra det daværende Forskningsudvalg var til Society for Academic Primary Care (SAPC) i Bristol. En konference, hvor den nyeste forskning og de hotteste forskere inden for almen medicin i Storbritannien var repræsenteret...

  19. Genome-wide endogenous DAF-16/FOXO recruitment dynamics during lowered insulin signalling in C. elegans.

    Science.gov (United States)

    Kumar, Neeraj; Jain, Vaibhav; Singh, Anupama; Jagtap, Urmila; Verma, Sonia; Mukhopadhyay, Arnab

    2015-12-08

    Lowering insulin-IGF-1-like signalling (IIS) activates FOXO transcription factors (TF) to extend life span across species. To study the dynamics of FOXO chromatin occupancy under this condition in C. elegans, we report the first recruitment profile of endogenous DAF-16 and show that the response is conserved. DAF-16 predominantly acts as a transcriptional activator and binding within the 0.5 kb promoter-proximal region results in maximum induction of downstream targets that code for proteins involved in detoxification and longevity. Interestingly, genes that are activated under low IIS already have higher DAF-16 recruited to their promoters in WT. DAF-16 binds to variants of the FOXO consensus sequence in the promoter proximal regions of genes that are exclusively targeted during low IIS. We also define a set of 'core' direct targets, after comparing multiple studies, which tend to co-express and contribute robustly towards IIS-associated phenotypes. Additionally, we show that nuclear hormone receptor DAF-12 as well as zinc-finger TF EOR-1 may bind DNA in close proximity to DAF-16 and distinct TF classes that are direct targets of DAF-16 may be instrumental in regulating its indirect targets. Together, our study provides fundamental insights into the transcriptional biology of FOXO/DAF-16 and gene regulation downstream of the IIS pathway.

  20. Cell-nonautonomous signaling of FOXO/DAF-16 to the stem cells of Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Wenjing Qi

    Full Text Available In Caenorhabditis elegans (C. elegans, the promotion of longevity by the transcription factor DAF-16 requires reduced insulin/IGF receptor (IIR signaling or the ablation of the germline, although the reason for the negative impact of germ cells is unknown. FOXO/DAF-16 activity inhibits germline proliferation in both daf-2 mutants and gld-1 tumors. In contrast to its function as a germline tumor suppressor, we now provide evidence that somatic DAF-16 in the presence of IIR signaling can also result in tumorigenic activity, which counteracts robust lifespan extension. In contrast to the cell-autonomous IIR signaling, which is required for larval germline proliferation, activation of DAF-16 in the hypodermis results in hyperplasia of the germline and disruption of the surrounding basement membrane. SHC-1 adaptor protein and AKT-1 kinase antagonize, whereas AKT-2 and SGK-1 kinases promote, this cell-nonautonomous DAF-16 function. Our data suggest that a functional balance of DAF-16 activities in different tissues determines longevity and reveals a novel, cell-nonautonomous role of FOXO/DAF-16 to affect stem cells.

  1. Cell-Nonautonomous Signaling of FOXO/DAF-16 to the Stem Cells of Caenorhabditis elegans

    Science.gov (United States)

    Qi, Wenjing; Huang, Xu; Neumann-Haefelin, Elke; Schulze, Ekkehard; Baumeister, Ralf

    2012-01-01

    In Caenorhabditis elegans (C. elegans), the promotion of longevity by the transcription factor DAF-16 requires reduced insulin/IGF receptor (IIR) signaling or the ablation of the germline, although the reason for the negative impact of germ cells is unknown. FOXO/DAF-16 activity inhibits germline proliferation in both daf-2 mutants and gld-1 tumors. In contrast to its function as a germline tumor suppressor, we now provide evidence that somatic DAF-16 in the presence of IIR signaling can also result in tumorigenic activity, which counteracts robust lifespan extension. In contrast to the cell-autonomous IIR signaling, which is required for larval germline proliferation, activation of DAF-16 in the hypodermis results in hyperplasia of the germline and disruption of the surrounding basement membrane. SHC-1 adaptor protein and AKT-1 kinase antagonize, whereas AKT-2 and SGK-1 kinases promote, this cell-nonautonomous DAF-16 function. Our data suggest that a functional balance of DAF-16 activities in different tissues determines longevity and reveals a novel, cell-nonautonomous role of FOXO/DAF-16 to affect stem cells. PMID:22916022

  2. The Deubiquitylase MATH-33 Controls DAF-16 Stability and Function in Metabolism and Longevity.

    Science.gov (United States)

    Heimbucher, Thomas; Liu, Zheng; Bossard, Carine; McCloskey, Richard; Carrano, Andrea C; Riedel, Christian G; Tanasa, Bogdan; Klammt, Christian; Fonslow, Bryan R; Riera, Celine E; Lillemeier, Bjorn F; Kemphues, Kenneth; Yates, John R; O'Shea, Clodagh; Hunter, Tony; Dillin, Andrew

    2015-07-07

    FOXO family transcription factors are downstream effectors of Insulin/IGF-1 signaling (IIS) and major determinants of aging in organisms ranging from worms to man. The molecular mechanisms that actively promote DAF16/FOXO stability and function are unknown. Here we identify the deubiquitylating enzyme MATH-33 as an essential DAF-16 regulator in IIS, which stabilizes active DAF-16 protein levels and, as a consequence, influences DAF-16 functions, such as metabolism, stress response, and longevity in C. elegans. MATH-33 associates with DAF-16 in cellulo and in vitro. MATH-33 functions as a deubiquitylase by actively removing ubiquitin moieties from DAF-16, thus counteracting the action of the RLE-1 E3-ubiquitin ligase. Our findings support a model in which MATH-33 promotes DAF-16 stability in response to decreased IIS by directly modulating its ubiquitylation state, suggesting that regulated oscillations in the stability of DAF-16 protein play an integral role in controlling processes such as metabolism and longevity. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. DAF-16/FOXO employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity

    Science.gov (United States)

    Riedel, Christian G.; Dowen, Robert H.; Lourenco, Guinevere F.; Kirienko, Natalia V.; Heimbucher, Thomas; West, Jason A.; Bowman, Sarah K.; Kingston, Robert E.; Dillin, Andrew; Asara, John M.; Ruvkun, Gary

    2013-01-01

    Organisms are constantly challenged by stresses and privations and require adaptive responses for their survival. The transcription factor DAF-16/FOXO is central nexus in these responses, but despite its importance little is known about how it regulates its target genes. Proteomic identification of DAF-16/FOXO binding partners in Caenorhabditis elegans and their subsequent functional evaluation by RNA interference (RNAi) revealed several candidate DAF-16/FOXO cofactors, most notably the chromatin remodeller SWI/SNF. DAF-16/FOXO and SWI/SNF form a complex and globally colocalize at DAF-16/FOXO target promoters. We show that specifically for gene-activation, DAF-16/FOXO depends on SWI/SNF, facilitating SWI/SNF recruitment to target promoters, in order to activate transcription by presumed remodelling of local chromatin. For the animal, this translates into an essential role of SWI/SNF for DAF-16/FOXO-mediated processes, i.e. dauer formation, stress resistance, and the promotion of longevity. Thus we give insight into the mechanisms of DAF-16/FOXO-mediated transcriptional regulation and establish a critical link between ATP-dependent chromatin remodelling and lifespan regulation. PMID:23604319

  4. DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.

    Science.gov (United States)

    Mueller, Michael M; Castells-Roca, Laia; Babu, Vipin; Ermolaeva, Maria A; Müller, Roman-Ulrich; Frommolt, Peter; Williams, Ashley B; Greiss, Sebastian; Schneider, Jennifer I; Benzing, Thomas; Schermer, Bernhard; Schumacher, Björn

    2014-12-01

    Genome maintenance defects cause complex disease phenotypes characterized by developmental failure, cancer susceptibility and premature ageing. It remains poorly understood how DNA damage responses function during organismal development and maintain tissue functionality when DNA damage accumulates with ageing. Here we show that the FOXO transcription factor DAF-16 is activated in response to DNA damage during development, whereas the DNA damage responsiveness of DAF-16 declines with ageing. We find that in contrast to its established role in mediating starvation arrest, DAF-16 alleviates DNA-damage-induced developmental arrest and even in the absence of DNA repair promotes developmental growth and enhances somatic tissue functionality. We demonstrate that the GATA transcription factor EGL-27 co-regulates DAF-16 target genes in response to DNA damage and together with DAF-16 promotes developmental growth. We propose that EGL-27/GATA activity specifies DAF-16-mediated DNA damage responses to enable developmental progression and to prolong tissue functioning when DNA damage persists.

  5. The C. elegans Ortholog of USP7 controls DAF-16 stability in Insulin/IGF-1-like signaling.

    Science.gov (United States)

    Heimbucher, Thomas; Hunter, Tony

    2015-01-01

    FOXO family transcription factors are downstream effectors of Insulin/IGF-1 signaling (IIS) and are regulated by posttranslational modification and coregulators, including components of the ubiquitin-proteasome system (UPS). Cofactors promoting DAF-16/FOXO protein stability and function in IIS have not been described yet. In a recent study, we have identified the deubiquitylating enzyme MATH-33, the ortholog of mammalian USP7/HAUSP, as an essential DAF-16 coregulator. We found that MATH-33 actively stabilizes DAF-16 protein levels when IIS is downregulated. Here we discuss how DAF-16/FOXO transcription factors are regulated by the UPS, in particular by the interplay of E3-ubiquitin ligases and deubiquitylating enzymes, which is critical for balancing DAF-16/FOXO activity and degradation. Recent findings raise the intriguing possibility that regulated oscillations in DAF-16/FOXO steady state levels play an integral role in mechanisms controlling healthspan and lifespan extension.

  6. Towards understanding the lifespan extension by reduced insulin signaling: bioinformatics analysis of DAF-16/FOXO direct targets in Caenorhabditis elegans.

    Science.gov (United States)

    Li, Yan-Hui; Zhang, Gai-Gai

    2016-04-12

    DAF-16, the C. elegans FOXO transcription factor, is an important determinant in aging and longevity. In this work, we manually curated FOXODB http://lyh.pkmu.cn/foxodb/, a database of FOXO direct targets. It now covers 208 genes. Bioinformatics analysis on 109 DAF-16 direct targets in C. elegans found interesting results. (i) DAF-16 and transcription factor PQM-1 co-regulate some targets. (ii) Seventeen targets directly regulate lifespan. (iii) Four targets are involved in lifespan extension induced by dietary restriction. And (iv) DAF-16 direct targets might play global roles in lifespan regulation.

  7. Dansk Almenmedicinsk Forskningsdag - DAF 2015

    DEFF Research Database (Denmark)

    Geyti, Christine Ladegaard

    2015-01-01

    Den 18. marts blev Dansk Almenmedicinsk Forskningsdag (DAF) afholdt i København. Arrangementet foregik i Domus Medicas flotte adelspalæ med prægtige lysekroner og hyggelige opholdsrum med bløde lænestole og gamle bøger op og ned ad væggene. Der blev nu ikke megen tid til at slænge sig, for progra......Den 18. marts blev Dansk Almenmedicinsk Forskningsdag (DAF) afholdt i København. Arrangementet foregik i Domus Medicas flotte adelspalæ med prægtige lysekroner og hyggelige opholdsrum med bløde lænestole og gamle bøger op og ned ad væggene. Der blev nu ikke megen tid til at slænge sig...

  8. Identification of hookworm DAF-16/FOXO response elements and direct gene targets.

    Directory of Open Access Journals (Sweden)

    Xin Gao

    2010-08-01

    Full Text Available The infective stage of the parasitic nematode hookworm is developmentally arrested in the environment and needs to infect a specific host to complete its life cycle. The canine hookworm (Ancylostoma caninum is an excellent model for investigating human hookworm infections. The transcription factor of A. caninum, Ac-DAF-16, which has a characteristic fork head or "winged helix" DNA binding domain (DBD, has been implicated in the resumption of hookworm development in the host. However, the precise roles of Ac-DAF-16 in hookworm parasitism and its downstream targets are unknown. In the present study, we combined molecular techniques and bioinformatics to identify a group of Ac-DAF-16 binding sites and target genes.The DNA binding domain of Ac-DAF-16 was used to select genomic fragments by in vitro genomic selection. Twenty four bound genomic fragments were analyzed for the presence of the DAF-16 family binding element (DBE and possible alternative Ac-DAF-16 bind motifs. The 22 genes linked to these genomic fragments were identified using bioinformatics tools and defined as candidate direct gene targets of Ac-DAF-16. Their developmental stage-specific expression patterns were examined. Also, a new putative DAF-16 binding element was identified.Our results show that Ac-DAF-16 is involved in diverse biological processes throughout hookworm development. Further investigation of these target genes will provide insights into the molecular basis by which Ac-DAF-16 regulates its downstream gene network in hookworm infection.

  9. Longevity Genes Revealed by Integrative Analysis of Isoform-Specific daf-16/FoxO Mutants of Caenorhabditis elegans.

    Science.gov (United States)

    Chen, Albert Tzong-Yang; Guo, Chunfang; Itani, Omar A; Budaitis, Breane G; Williams, Travis W; Hopkins, Christopher E; McEachin, Richard C; Pande, Manjusha; Grant, Ana R; Yoshina, Sawako; Mitani, Shohei; Hu, Patrick J

    2015-10-01

    FoxO transcription factors promote longevity across taxa. How they do so is poorly understood. In the nematode Caenorhabditis elegans, the A- and F-isoforms of the FoxO transcription factor DAF-16 extend life span in the context of reduced DAF-2 insulin-like growth factor receptor (IGFR) signaling. To elucidate the mechanistic basis for DAF-16/FoxO-dependent life span extension, we performed an integrative analysis of isoform-specific daf-16/FoxO mutants. In contrast to previous studies suggesting that DAF-16F plays a more prominent role in life span control than DAF-16A, isoform-specific daf-16/FoxO mutant phenotypes and whole transcriptome profiling revealed a predominant role for DAF-16A over DAF-16F in life span control, stress resistance, and target gene regulation. Integration of these datasets enabled the prioritization of a subset of 92 DAF-16/FoxO target genes for functional interrogation. Among 29 genes tested, two DAF-16A-specific target genes significantly influenced longevity. A loss-of-function mutation in the conserved gene gst-20, which is induced by DAF-16A, reduced life span extension in the context of daf-2/IGFR RNAi without influencing longevity in animals subjected to control RNAi. Therefore, gst-20 promotes DAF-16/FoxO-dependent longevity. Conversely, a loss-of-function mutation in srr-4, a gene encoding a seven-transmembrane-domain receptor family member that is repressed by DAF-16A, extended life span in control animals, indicating that DAF-16/FoxO may extend life span at least in part by reducing srr-4 expression. Our discovery of new longevity genes underscores the efficacy of our integrative strategy while providing a general framework for identifying specific downstream gene regulatory events that contribute substantially to transcription factor functions. As FoxO transcription factors have conserved functions in promoting longevity and may be dysregulated in aging-related diseases, these findings promise to illuminate fundamental

  10. Increased deposition of C3b on red cells with low CR1 and CD55 in a malaria-endemic region of western Kenya: Implications for the development of severe anemia

    Directory of Open Access Journals (Sweden)

    Odera Michael M

    2008-08-01

    Full Text Available Abstract Background Severe anemia due to Plasmodium falciparum malaria is a major cause of mortality among young children in western Kenya. The factors that lead to the age-specific incidence of this anemia are unknown. Previous studies have shown an age-related expression of red cell complement regulatory proteins, which protect erythrocytes from autologous complement attack and destruction. Our primary objective was to determine whether in a malaria-endemic area red cells with low levels of complement regulatory proteins are at increased risk for complement (C3b deposition in vivo. Secondarily, we studied the relationship between red cell complement regulatory protein levels and hemoglobin levels. Methods Three hundred and forty-two life-long residents of a malaria-holoendemic region of western Kenya were enrolled in a cross-sectional study and stratified by age. We measured red cell C3b, CR1, CD55, and immune complex binding capacity by flow cytometry. Individuals who were positive for malaria were treated and blood was collected when they were free of parasitemia. Analysis of variance was used to identify independent variables associated with the %C3b-positive red cells and the hemoglobin level. Results Individuals between the ages of 6 and 36 months had the lowest red cell CR1, highest %C3b-positive red cells, and highest parasite density. Malaria prevalence also reached its peak within this age group. Among children ≤ 24 months of age the %C3b-positive red cells was usually higher in individuals who were treated for malaria than in uninfected individuals with similarly low red cell CR1 and CD55. The variables that most strongly influenced the %C3b-positive red cells were age, malaria status, and red cell CD55 level. Although it did not reach statistical significance, red cell CR1 was more important than red cell CD55 among individuals treated for malaria. The variables that most strongly influenced the hemoglobin level were age, the %C3b

  11. C. elegans SIRT6/7 homolog SIR-2.4 promotes DAF-16 relocalization and function during stress.

    Science.gov (United States)

    Chiang, Wei-Chung; Tishkoff, Daniel X; Yang, Bo; Wilson-Grady, Joshua; Yu, Xiaokun; Mazer, Travis; Eckersdorff, Mark; Gygi, Steven P; Lombard, David B; Hsu, Ao-Lin

    2012-09-01

    FoxO transcription factors and sirtuin family deacetylases regulate diverse biological processes, including stress responses and longevity. Here we show that the Caenorhabditis elegans sirtuin SIR-2.4--homolog of mammalian SIRT6 and SIRT7 proteins--promotes DAF-16-dependent transcription and stress-induced DAF-16 nuclear localization. SIR-2.4 is required for resistance to multiple stressors: heat shock, oxidative insult, and proteotoxicity. By contrast, SIR-2.4 is largely dispensable for DAF-16 nuclear localization and function in response to reduced insulin/IGF-1-like signaling. Although acetylation is known to regulate localization and activity of mammalian FoxO proteins, this modification has not been previously described on DAF-16. We find that DAF-16 is hyperacetylated in sir-2.4 mutants. Conversely, DAF-16 is acetylated by the acetyltransferase CBP-1, and DAF-16 is hypoacetylated and constitutively nuclear in response to cbp-1 inhibition. Surprisingly, a SIR-2.4 catalytic mutant efficiently rescues the DAF-16 localization defect in sir-2.4 null animals. Acetylation of DAF-16 by CBP-1 in vitro is inhibited by either wild-type or mutant SIR-2.4, suggesting that SIR-2.4 regulates DAF-16 acetylation indirectly, by preventing CBP-1-mediated acetylation under stress conditions. Taken together, our results identify SIR-2.4 as a critical regulator of DAF-16 specifically in the context of stress responses. Furthermore, they reveal a novel role for acetylation, modulated by the antagonistic activities of CBP-1 and SIR-2.4, in modulating DAF-16 localization and function.

  12. Strongyloides stercoralis daf-2 encodes a divergent ortholog of Caenorhabditis elegans DAF-2.

    Science.gov (United States)

    Massey, Holman C; Ranjit, Najju; Stoltzfus, Jonathan D; Lok, James B

    2013-06-01

    We hypothesise that developmental arrest in infectious larvae of parasitic nematodes is regulated by signalling pathways homologous to Caenorhabditis elegans DAF (dauer formation) pathways. Alignment of Strongyloides stercoralis (Ss) DAF-2 with DAF-2 of C. elegans and homologs of other species shows that most structural motifs in these insulin-like receptors are conserved. However, the catalytic domain of Ss-DAF-2 contains two substitutions (Q1242 and Q1256), that would result in constitutive dauer formation in C. elegans or diabetes in vertebrate animals. Ss-daf-2 also shows two alternately spliced isoforms, the constitutively expressed Ss-daf-2a, and Ss-daf-2b, which is only expressed in stages leading to parasitism. Copyright © 2013 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  13. Synthetic DAF-12 modulators with potential use in controlling the nematode life cycle.

    Science.gov (United States)

    Dansey, María V; Alvarez, Lautaro D; Samaja, Gisela; Escudero, Daiana S; Veleiro, Adriana S; Pecci, Adalí; Castro, Olga A; Burton, Gerardo

    2015-01-01

    Dafachronic acids (DAs) are 3-keto cholestenoic acids bearing a carboxylic acid moiety at the end of the steroid side chain. These compounds interact with the DAF-12 receptor, a ligand-dependent transcription factor that acts as a molecular switch mediating the choice between arrest at diapause or progression to reproductive development and adult lifespan in different nematodes. Recently, we reported that the 27-nor-Δ4-DA was able to directly activate DAF-12 in a transactivation cell-based luciferase assay and rescued the Mig phenotype of daf-9(rh50) Caenorhabditis elegans mutants. In the present paper, to investigate further the relationship between the structure of the steroid side chain and DAF-12 activity, we evaluated the in vitro and in vivo activity of Δ4-DA analogues with modified side chains using transactivation cell-based assays and daf-9(dh6) C. elegans mutants. Our results revealed that introduction of a 24,25-double bond on the cholestenoic acid side chain did not affect DAF-12 activity, whereas shortening the side chain lowered the activity. Most interestingly, the C24 alcohol 24-hydroxy-4-cholen-3-one (6) was an antagonist of the DAF-12 receptor both in vitro and in vivo.

  14. Insulin Signaling-independent Activation of DAF-16 Shapes the Transcriptome during Normal Aging

    OpenAIRE

    Zhang, Yan-Ping; Liang, Chung-Yi; Hsu, Ao-Lin; Li, Shang-Tong; Zhang, Pan; Dong, Meng-Qiu; Zhao, Han-Qing

    2018-01-01

    The roles and regulatory mechanisms of transriptome changes during aging are unclear. It has been proposed that the transcriptome suffers decay during aging owing to age-associated down-regulation of transcription factors. In this study, we characterized the role of a transcription factor DAF-16, which is a highly conserved lifespan regulator, in the normal aging process of Caenorhabditis elegans. We found that DAF-16 translocates into the nucleus in aged wild-type worms and activates the exp...

  15. Calycosin promotes lifespan in Caenorhabditis elegans through insulin signaling pathway via daf-16, age-1 and daf-2.

    Science.gov (United States)

    Lu, Lulu; Zhao, Xuan; Zhang, Jianyong; Li, Miao; Qi, Yonghao; Zhou, Lijun

    2017-07-01

    The naturally occurring calycosin is a known antioxidant that prevents redox imbalance in organisms. However, calycosin's effect on lifespan and its physiological molecular mechanisms are not yet well understood. In this study, we demonstrated that calycosin could prolong the lifespan of Caenorhabditis elegans, and that such extension was associated with its antioxidant capability as well as its ability to enhance stress resistance and reduce ROS (reactive oxygen species) accumulation. To explore mechanisms of this longevity effect, we assessed the impact of calycosin on lifespans of insulin-signaling impaired worms: daf-2, age-1, and daf-16 mutants. We found that calycosin did not alter the lifespan of all three mutants, thereby suggesting that calycosin requires insulin signaling to promote lifespan extension. On the other hand, we observed that calycosin could enhance the nuclear translocation of the core transcription factor DAF-16/FoXO instead of the conserved stress-responsive transcription factor SKN-1/Nrf-2. This observation is consistent with the understanding that the nuclear localized DAF-16 up-regulates its downstream targets sod-3, ctl-1, and hsp-16.2. Lastly, it is also noteworthy that the longevity effect of calycosin is likely not associated with the calorie restriction mechanism. Collectively, our results strongly suggest that calycosin could function as an antioxidant to extend the lifespan of C. elegans by enhancing nucleus translocation of DAF-16 through the insulin-signaling pathway. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  16. Sterol-derived hormone(s controls entry into diapause in Caenorhabditis elegans by consecutive activation of DAF-12 and DAF-16.

    Directory of Open Access Journals (Sweden)

    Vitali Matyash

    2004-10-01

    Full Text Available Upon starvation or overcrowding, Caenorhabditis elegans interrupts its reproductive cycle and forms a specialised larva called dauer (enduring. This process is regulated by TGF-beta and insulin-signalling pathways and is connected with the control of life span through the insulin pathway components DAF-2 and DAF-16. We found that replacing cholesterol with its methylated metabolite lophenol induced worms to form dauer larvae in the presence of food and low population density. Our data indicate that methylated sterols do not actively induce the dauer formation but rather that the reproductive growth requires a cholesterol-derived hormone that cannot be produced from methylated sterols. Using the effect of lophenol on growth, we have partially purified activity, named gamravali, which promotes the reproduction. In addition, the effect of lophenol allowed us to determine the role of sterols during dauer larva formation and longevity. In the absence of gamravali, the nuclear hormone receptor DAF-12 is activated and thereby initiates the dauer formation program. Active DAF-12 triggers in neurons the nuclear import of DAF-16, a forkhead domain transcription factor that contributes to dauer differentiation. This hormonal control of DAF-16 activation is, however, independent of insulin signalling and has no influence on life span.

  17. daf-31 encodes the catalytic subunit of N alpha-acetyltransferase that regulates Caenorhabditis elegans development, metabolism and adult lifespan.

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    Di Chen

    2014-10-01

    Full Text Available The Caenorhabditis elegans dauer larva is a facultative state of diapause. Mutations affecting dauer signal transduction and morphogenesis have been reported. Of these, most that result in constitutive formation of dauer larvae are temperature-sensitive (ts. The daf-31 mutant was isolated in genetic screens looking for novel and underrepresented classes of mutants that form dauer and dauer-like larvae non-conditionally. Dauer-like larvae are arrested in development and have some, but not all, of the normal dauer characteristics. We show here that daf-31 mutants form dauer-like larvae under starvation conditions but are sensitive to SDS treatment. Moreover, metabolism is shifted to fat accumulation in daf-31 mutants. We cloned the daf-31 gene and it encodes an ortholog of the arrest-defective-1 protein (ARD1 that is the catalytic subunit of the major N alpha-acetyltransferase (NatA. A daf-31 promoter::GFP reporter gene indicates daf-31 is expressed in multiple tissues including neurons, pharynx, intestine and hypodermal cells. Interestingly, overexpression of daf-31 enhances the longevity phenotype of daf-2 mutants, which is dependent on the forkhead transcription factor (FOXO DAF-16. We demonstrate that overexpression of daf-31 stimulates the transcriptional activity of DAF-16 without influencing its subcellular localization. These data reveal an essential role of NatA in controlling C. elegans life history and also a novel interaction between ARD1 and FOXO transcription factors, which may contribute to understanding the function of ARD1 in mammals.

  18. daf-31 encodes the catalytic subunit of N alpha-acetyltransferase that regulates Caenorhabditis elegans development, metabolism and adult lifespan.

    Science.gov (United States)

    Chen, Di; Zhang, Jiuli; Minnerly, Justin; Kaul, Tiffany; Riddle, Donald L; Jia, Kailiang

    2014-10-01

    The Caenorhabditis elegans dauer larva is a facultative state of diapause. Mutations affecting dauer signal transduction and morphogenesis have been reported. Of these, most that result in constitutive formation of dauer larvae are temperature-sensitive (ts). The daf-31 mutant was isolated in genetic screens looking for novel and underrepresented classes of mutants that form dauer and dauer-like larvae non-conditionally. Dauer-like larvae are arrested in development and have some, but not all, of the normal dauer characteristics. We show here that daf-31 mutants form dauer-like larvae under starvation conditions but are sensitive to SDS treatment. Moreover, metabolism is shifted to fat accumulation in daf-31 mutants. We cloned the daf-31 gene and it encodes an ortholog of the arrest-defective-1 protein (ARD1) that is the catalytic subunit of the major N alpha-acetyltransferase (NatA). A daf-31 promoter::GFP reporter gene indicates daf-31 is expressed in multiple tissues including neurons, pharynx, intestine and hypodermal cells. Interestingly, overexpression of daf-31 enhances the longevity phenotype of daf-2 mutants, which is dependent on the forkhead transcription factor (FOXO) DAF-16. We demonstrate that overexpression of daf-31 stimulates the transcriptional activity of DAF-16 without influencing its subcellular localization. These data reveal an essential role of NatA in controlling C. elegans life history and also a novel interaction between ARD1 and FOXO transcription factors, which may contribute to understanding the function of ARD1 in mammals.

  19. Ida-1, the Caenorhabditis elegans orthologue of mammalian diabetes autoantigen IA-2, potentially acts as a common modulator between Parkinson's disease and Diabetes: role of Daf-2/Daf-16 insulin like signalling pathway.

    Science.gov (United States)

    Fatima, Soobiya; Haque, Rizwanul; Jadiya, Pooja; Shamsuzzama; Kumar, Lalit; Nazir, Aamir

    2014-01-01

    The lack of cure to age associated Parkinson's disease (PD) has been challenging the efforts of researchers as well as health care providers. Recent evidences suggest that diabetic patients tend to show a higher future risk for PD advocating a strong correlation between PD and Diabetes, thus making it intriguing to decipher common genetic cues behind these ailments. We carried out studies on ida-1, the C. elegans orthologue of mammalian type-1 diabetes auto-antigen IA-2 towards achieving its functional workup vis-à-vis various associated endpoints of PD and Diabetes. Employing transgenic C. elegans strain expressing "human" alpha synuclein (NL5901) under normal and increased glucose concentrations, we studied aggregation of alpha synuclein, content of dopamine, expression of dopamine transporter, content of reactive oxygen species, locomotor activity, nuclear translocation of FOXO transcription factor Daf-16, and quantification of Daf2/Daf-16 mRNA. Our findings indicate that ida-1 affords protection in the studied disease conditions as absence of ida-1 resulted in higher alpha-synuclein aggregation under conditions that mimic the blood glucose levels of diabetic patients. We also observed reduced dopamine content, decreased motility, defective Daf-16 translocation and reduced expression of Daf-2 and Daf-16. Our studies establish important function of ida-1 as a modulator in Daf-2/Daf-16 insulin like signalling pathway thus possibly being a common link between PD and Diabetes.

  20. RNAi screen of DAF-16/FOXO target genes in C. elegans links pathogenesis and dauer formation.

    Directory of Open Access Journals (Sweden)

    Victor L Jensen

    2010-12-01

    Full Text Available The DAF-16/FOXO transcription factor is the major downstream output of the insulin/IGF1R signaling pathway controlling C. elegans dauer larva development and aging. To identify novel downstream genes affecting dauer formation, we used RNAi to screen candidate genes previously identified to be regulated by DAF-16. We used a sensitized genetic background [eri-1(mg366; sdf-9(m708], which enhances both RNAi efficiency and constitutive dauer formation (Daf-c. Among 513 RNAi clones screened, 21 displayed a synthetic Daf-c (SynDaf phenotype with sdf-9. One of these genes, srh-100, was previously identified to be SynDaf, but twenty have not previously been associated with dauer formation. Two of the latter genes, lys-1 and cpr-1, are known to participate in innate immunity and six more are predicted to do so, suggesting that the immune response may contribute to the dauer decision. Indeed, we show that two of these genes, lys-1 and clc-1, are required for normal resistance to Staphylococcus aureus. clc-1 is predicted to function in epithelial cohesion. Dauer formation exhibited by daf-8(m85, sdf-9(m708, and the wild-type N2 (at 27°C were all enhanced by exposure to pathogenic bacteria, while not enhanced in a daf-22(m130 background. We conclude that knockdown of the genes required for proper pathogen resistance increases pathogenic infection, leading to increased dauer formation in our screen. We propose that dauer larva formation is a behavioral response to pathogens mediated by increased dauer pheromone production.

  1. Redox-dependent control of FOXO/DAF-16 by transportin-1.

    Science.gov (United States)

    Putker, Marrit; Madl, Tobias; Vos, Harmjan R; de Ruiter, Hesther; Visscher, Marieke; van den Berg, Maaike C W; Kaplan, Mohammed; Korswagen, Hendrik C; Boelens, Rolf; Vermeulen, Michiel; Burgering, Boudewijn M T; Dansen, Tobias B

    2013-02-21

    Forkhead box O (FOXO; DAF-16 in worms) transcription factors, which are of vital importance in cell-cycle control, stress resistance, tumor suppression, and organismal lifespan, are largely regulated through nucleo-cytoplasmic shuttling. Insulin signaling keeps FOXO/DAF-16 cytoplasmic, and hence transcriptionally inactive. Conversely, as in loss of insulin signaling, reactive oxygen species (ROS) can activate FOXO/DAF-16 through nuclear accumulation. How ROS regulate the nuclear translocation of FOXO/DAF-16 is largely unknown. Cysteine oxidation can stabilize protein-protein interactions through the formation of disulfide-bridges when cells encounter ROS. Using a proteome-wide screen that identifies ROS-induced mixed disulfide-dependent complexes, we discovered several interaction partners of FOXO4, one of which is the nuclear import receptor transportin-1. We show that disulfide formation with transportin-1 is required for nuclear localization and the activation of FOXO4/DAF-16 induced by ROS, but not by the loss of insulin signaling. This molecular mechanism for nuclear shuttling is conserved in C. elegans and directly connects redox signaling to the longevity protein FOXO/DAF-16. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. A splice acceptor mutation in C. elegans daf-19/Rfx disrupts functional specialization of male-specific ciliated neurons but does not affect ciliogenesis.

    Science.gov (United States)

    Wells, Kristen L; Rowneki, Mazhgan; Killian, Darrell J

    2015-04-01

    RFX transcription factors are master regulators of ciliogenesis in diverse animal species. The sole Caenorhabditis elegans RFX homolog, DAF-19, plays at least two roles in the formation of functional cilia. The DAF-19(C) isoform is required for ciliogenesis and the DAF-19(M) isoform is required for the functional specialization of a subset of male-specific ciliated neurons called PKD neurons. Here we report the identification of a novel mutation, daf-19(sm129), which disrupts the functional specification of PKD neurons and thus suggests that daf-19m activity is compromised. However, ciliogenesis is not disrupted in daf-19(sm129) mutants suggesting that daf-19c activity is retained. The sm129 mutation disrupts a splice acceptor site adjacent to an exon common to the daf-19c and daf-19m isoforms resulting in aberrant splicing in a proportion of transcripts. While aberrant splicing of daf-19c to upstream cryptic sites results in in-frame and functional products, a large proportion of daf-19m mRNAs include the entire upstream intron, which introduces a frameshift and stop codons. At least 15% of disease-causing mutations affect splicing of the gene bearing the mutation, thus it is important to understand the consequences of splice site mutations on gene function. However, predicting the effects of a splice site mutation remains difficult and experimental determination is still required. Using daf-19(sm129) as a model, our results suggest that this problem is exacerbated when a splice acceptor mutation is used by multiple isoforms of the same gene because the effects on each isoform can be dramatically different. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Hc-daf-2 encodes an insulin-like receptor kinase in the barber's pole worm, Haemonchus contortus, and restores partial dauer regulation.

    Science.gov (United States)

    Li, Facai; Lok, James B; Gasser, Robin B; Korhonen, Pasi K; Sandeman, Mark R; Shi, Deshi; Zhou, Rui; Li, Xiangrui; Zhou, Yanqin; Zhao, Junlong; Hu, Min

    2014-06-01

    Infective L3s (iL3s) of parasitic nematodes share common behavioural, morphological and developmental characteristics with the developmentally arrested (dauer) larvae of the free-living nematode Caenorhabditis elegans. It is proposed that similar molecular mechanisms regulate entry into or exit from the dauer stage in C. elegans, and the transition from free-living to parasitic forms of parasitic nematodes. In C. elegans, one of the key factors regulating the dauer transition is the insulin-like receptor (designated Ce-DAF-2) encoded by the gene Ce-daf-2. However, nothing is known about DAF-2 homologues in most parasitic nematodes. Here, using a PCR-based approach, we identified and characterised a gene (Hc-daf-2) and its inferred product (Hc-DAF-2) in Haemonchus contortus (a socioeconomically important parasitic nematode of ruminants). The sequence of Hc-DAF-2 displays significant sequence homology to insulin receptors (IR) in both vertebrates and invertebrates, and contains conserved structural domains. A sequence encoding an important proteolytic motif (RKRR) identified in the predicted peptide sequence of Hc-DAF-2 is consistent with that of the human IR, suggesting that it is involved in the formation of the IR complex. The Hc-daf-2 gene was transcribed in all life stages of H. contortus, with a significant up-regulation in the iL3 compared with other stages. To compare patterns of expression between Hc-daf-2 and Ce-daf-2, reporter constructs fusing the Ce-daf-2 or Hc-daf-2 promoter to sequence encoding GFP were microinjected into the N2 strain of C. elegans, and transgenic lines were established and examined. Both genes showed similar patterns of expression in amphidial (head) neurons, which relate to sensation and signal transduction. Further study by heterologous genetic complementation in a daf-2-deficient strain of C. elegans (CB1370) showed partial rescue of function by Hc-daf-2. Taken together, these findings provide a first insight into the roles of Hc-daf

  4. Simulation environment architecture development using the DoDAF

    NARCIS (Netherlands)

    Berg, T. van den; Lutz, R.

    2015-01-01

    The US Department of Defense (DoD) Architecture Framework (DoDAF) provides a common approach for architecture description development. The primary use of DoDAF is capability development and system acquisition in the military domain. Although DoDAF was not designed to support the development of

  5. Study of local structure by DAFS

    International Nuclear Information System (INIS)

    Mizuki, Jun-ichiro

    1997-01-01

    We will describe a rather new X-ray structural technique, Diffraction Anomalous Fine Structure (DAFS), in which the Bragg diffraction intensities of a fixed momentum transfer is measured as a function of the incident X-ray energy. This technique can provide the same short-range structural information as XAFS. Because DAFS combines the capabilities of diffraction and XAFS into a single technique, it has two enhanced sensitivities compared to the separate technique. These are 'spatial selectivity' and 'site selectivity'. In this chapter semiconductor interface structure study as an example for spatial selectivity and structural study of high Tc superconductor as an example for site selectivity will be shown. (author)

  6. Selenite protects Caenorhabditis elegans from oxidative stress via DAF-16 and TRXR-1.

    Science.gov (United States)

    Li, Wen-Hsuan; Shi, Yeu-Ching; Chang, Chun-Han; Huang, Chi-Wei; Hsiu-Chuan Liao, Vivian

    2014-04-01

    Selenium is an essential micronutrient. In the present study, trace amount of selenite (0.01 μM) was evaluated for oxidative stress resistance and potential associated factors in Caenorhabditis elegans. Selenite-treated C. elegans showed an increased survival under oxidative stress and thermal stress compared to untreated controls. Further studies demonstrated that the significant stress resistance of selenite on C. elegans could be attributed to its in vivo free radical-scavenging ability. We also found that the oxidative and thermal stress resistance phenotypes by selenite were absent from the forkhead transcription factor daf-16 mutant worms. Moreover, selenite influenced the subcellular distribution of DAF-16 in C. elegans. Furthermore, selenite increased mRNA levels of stress-resistance-related proteins, including superoxide dismutase-3 and heat shock protein-16.2. Additionally, selenite (0.01 μM) upregulated expressions of transgenic C. elegans carrying sod-3::green fluorescent protein (GFP) and hsp-16.2::GFP, whereas this effect was abolished by feeding daf-16 RNA interference in C. elegans. Finally, unlike the wild-type N2 worms, the oxidative stress resistance phenotypes by selenite were both absent from the C. elegans selenoprotein trxr-1 mutant worms and trxr-1 mutants feeding with daf-16 RNA interference. These findings suggest that the antioxidant effects of selenite in C. elegans are mediated via DAF-16 and TRXR-1. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Regulation of Caenorhabditis elegans vitellogenesis by DAF-2/IIS through separable transcriptional and posttranscriptional mechanisms.

    Science.gov (United States)

    DePina, Ana S; Iser, Wendy B; Park, Sung-Soo; Maudsley, Stuart; Wilson, Mark A; Wolkow, Catherine A

    2011-07-12

    Evolutionary theories of aging propose that longevity evolves as a competition between reproduction and somatic maintenance for a finite pool of resources. Reproduction is thought to shorten lifespan by depleting resources from processes promoting somatic maintenance. Maternal yolk production, vitellogenesis, represents a significant maternal cost for reproduction and is suppressed under genetic and environmental conditions that extend lifespan. However, little is known about the pathways regulating vitellogenesis in response to prolongevity cues. In order to identify mechanisms that suppress vitellogenesis under prolongevity conditions, we studied factors regulating vitellogenesis in C. elegans nematodes. In C. elegans, vitellogenesis is depressed in the absence of insulin-like signaling (IIS). We found that the C. elegans daf-2/IIS pathway regulates vitellogenesis through two mechanisms. vit-2 transcript levels in daf-2 mutants were indirectly regulated through a germline-dependent signal, and could be rescued by introduction of daf-2(+) sperm. However, yolk protein (YP) levels in daf-2 mutants were also regulated by germline-independent posttranscriptional mechanisms. C. elegans vitellogenesis is regulated transcriptionally and posttranscriptionally in response to environmental and reproductive cues. The daf-2 pathway suppressed vitellogenesis through transcriptional mechanisms reflecting reproductive phenotypes, as well as distinct posttranscriptional mechanisms. This study reveals that pleiotropic effects of IIS pathway mutations can converge on a common downstream target, vitellogenesis, as a mechanism to modulate longevity.

  8. Regulation of Caenorhabditis elegans vitellogenesis by DAF-2/IIS through separable transcriptional and posttranscriptional mechanisms

    Directory of Open Access Journals (Sweden)

    Wilson Mark A

    2011-07-01

    Full Text Available Abstract Background Evolutionary theories of aging propose that longevity evolves as a competition between reproduction and somatic maintenance for a finite pool of resources. Reproduction is thought to shorten lifespan by depleting resources from processes promoting somatic maintenance. Maternal yolk production, vitellogenesis, represents a significant maternal cost for reproduction and is suppressed under genetic and environmental conditions that extend lifespan. However, little is known about the pathways regulating vitellogenesis in response to prolongevity cues. Results In order to identify mechanisms that suppress vitellogenesis under prolongevity conditions, we studied factors regulating vitellogenesis in C. elegans nematodes. In C. elegans, vitellogenesis is depressed in the absence of insulin-like signaling (IIS. We found that the C. elegans daf-2/IIS pathway regulates vitellogenesis through two mechanisms. vit-2 transcript levels in daf-2 mutants were indirectly regulated through a germline-dependent signal, and could be rescued by introduction of daf-2(+ sperm. However, yolk protein (YP levels in daf-2 mutants were also regulated by germline-independent posttranscriptional mechanisms. Conclusions C. elegans vitellogenesis is regulated transcriptionally and posttranscriptionally in response to environmental and reproductive cues. The daf-2 pathway suppressed vitellogenesis through transcriptional mechanisms reflecting reproductive phenotypes, as well as distinct posttranscriptional mechanisms. This study reveals that pleiotropic effects of IIS pathway mutations can converge on a common downstream target, vitellogenesis, as a mechanism to modulate longevity.

  9. Non-transcriptional Function of FOXO1/DAF-16 Contributes to Translesion DNA Synthesis.

    Science.gov (United States)

    Daitoku, Hiroaki; Kaneko, Yuta; Yoshimochi, Kenji; Matsumoto, Kaori; Araoi, Sho; Sakamaki, Jun-Ichi; Takahashi, Yuta; Fukamizu, Akiyoshi

    2016-08-22

    Forkhead box O (FOXO; DAF-16 in nematode) transcription factors activate a program of genes that control stress resistance, metabolism, and lifespan. Given the adverse impact of the stochastic DNA damage on organismal development and ageing, we examined the role of FOXO/DAF-16 in UV-induced DNA-damage response. Knockdown of FOXO1, but not FOXO3a, increases sensitivity to UV irradiation when exposed during S phase, suggesting a contribution of FOXO1 to translesion DNA synthesis (TLS), a replicative bypass of UV-induced DNA lesions. Actually, FOXO1 depletion results in a sustained activation of the ATR-Chk1 signaling and a reduction of PCNA monoubiquitination following UV irradiation. FOXO1 does not alter the expression of TLS-related genes but binds to the protein replication protein A (RPA1) that coats single-stranded DNA and acts as a scaffold for TLS. In Caenorhabditis elegans, daf-16 null mutants show UV-induced retardation in larval development and are rescued by overexpressing DAF-16 mutant lacking transactivation domain, but not substitution mutant unable to interact with RPA-1. Thus, our findings demonstrate that FOXO1/DAF-16 is a functional component in TLS independently of its transactivation activity. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  10. Nonautonomous Regulation of Neuronal Migration by Insulin Signaling, DAF-16/FOXO, and PAK-1

    Directory of Open Access Journals (Sweden)

    Lisa M. Kennedy

    2013-09-01

    Full Text Available Neuronal migration is essential for nervous system development in all organisms and is regulated in the nematode, C. elegans, by signaling pathways that are conserved in humans. Here, we demonstrate that the insulin/IGF-1-PI3K signaling pathway modulates the activity of the DAF-16/FOXO transcription factor to regulate the anterior migrations of the hermaphrodite-specific neurons (HSNs during embryogenesis of C. elegans. When signaling is reduced, DAF-16 is activated and promotes migration; conversely, when signaling is enhanced, DAF-16 is inactivated, and migration is inhibited. We show that DAF-16 acts nonautonomously in the hypodermis to promote HSN migration. Furthermore, we identify PAK-1, a p21-activated kinase, as a downstream mediator of insulin/IGF-1-DAF-16 signaling in the nonautonomous control of HSN migration. Because a FOXO-Pak1 pathway was recently shown to regulate mammalian neuronal polarity, our findings indicate that the roles of FOXO and Pak1 in neuronal migration are most likely conserved from C. elegans to higher organisms.

  11. Non-autonomous Regulation of Neuronal Migration by Insulin Signaling, DAF-16/FOXO and PAK-1

    Science.gov (United States)

    Kennedy, Lisa M.; Pham, Steven C.D.L.; Grishok, Alla

    2013-01-01

    SUMMARY Neuronal migration is essential for nervous system development in all organisms and is regulated in the nematode, C. elegans, by signaling pathways that are conserved in humans. Here, we demonstrate that the Insulin/IGF-1-PI3K signaling pathway modulates the activity of the DAF-16/FOXO transcription factor to promote the anterior migrations of the hermaphrodite-specific neurons (HSNs) during embryogenesis of C. elegans. When signaling is reduced, DAF-16 is activated and promotes migration, conversely, when signaling is enhanced, DAF-16 is inactivated and migration is inhibited. We show that DAF-16 acts non-autonomously in the hypodermis to promote HSN migration. Furthermore, we identify PAK-1, a p21-activated kinase, as a downstream mediator of Insulin/IGF-1-DAF-16 signaling in the non-autonomous control of HSN migration. As a FOXO-Pak1 pathway was recently shown to regulate mammalian neuronal polarity, our findings indicate that the roles of FOXO and Pak1 in neuronal migration are likely conserved from C. elegans to higher organisms. PMID:23994474

  12. Analysis list: daf-16 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available daf-16 Adult + ce10 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/daf-16.1....tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/daf-16.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/daf...-16.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/daf-16.Adult.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/Adult.gml ...

  13. Analysis list: daf-12 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available daf-12 Larvae + ce10 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/daf-12....1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/daf-12.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/daf...-12.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/daf-12.Larvae.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/Larvae.gml ...

  14. IFN-γ-producing NKT cells exacerbate sepsis by enhancing C5a generation via IL-10-mediated inhibition of CD55 expression on neutrophils.

    Science.gov (United States)

    Kim, Ji Hyung; Oh, Sae Jin; Ahn, Sehee; Chung, Doo Hyun

    2014-07-01

    A role for NKT cells has been implicated in sepsis, but the mechanism by which NKT cells contribute to sepsis remains unclear. Here, we examined WT and NKT-cell-deficient mice of C57BL/6 background during cecal ligation and puncture-induced sepsis. The levels of C5a, IFN-γ, and IL-10 were higher in the serum and peritoneal fluid of WT mice than in those of CD1d(-/-) mice, while the mortality rate was lower in CD1d(-/-) mice than in WT mice. C5a blockade decreased mortality of WT mice during sepsis, whereas it did not alter that of CD1d(-/-) mice. As assessed by intracellular staining, NKT cells expressed IFN-γ, while neutrophils expressed IL-10. Upon coculture, IL-10-deficient NKT cells enhanced IL-10 production by WT, but not IFN-γR-deficient, neutrophils. Meanwhile, CD1d(-/-) mice exhibited high CD55 expression on neutrophils during sepsis, whereas those cells from WT mice expressed minimal levels of CD55. Recombinant IL-10 administration into CD1d(-/-) mice reduced CD55 expression on neutrophils. Furthermore, adoptive transfer of sorted WT, but not IFN-γ-deficient, NKT cells into CD1d(-/-) mice suppressed CD55 expression on neutrophils, but increased IL-10 and C5a levels. Taken together, IFN-γ-producing NKT cells enhance C5a generation via IL-10-mediated inhibition of CD55 expression on neutrophils, thereby exacerbating sepsis. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Baicalein modulates stress-resistance and life span in C. elegans via SKN-1 but not DAF-16.

    Science.gov (United States)

    Havermann, Susannah; Humpf, Hans-Ulrich; Wätjen, Wim

    2016-09-01

    The flavonoid baicalein has been demonstrated to be an activator of the transcription factor Nrf2 in mammalian cell lines. We show that it further modulates the Nrf2 homolog SKN-1 in Caenorhabditis elegans and by this pathway mediates beneficial effects in the nematode: baicalein enhances the resistance of C. elegans against lethal thermal and sodium arsenite stress and dose-dependently prolongs the life span of the nematode. Using RNA interference against SKN-1 we were able to show that the induction of longevity and the enhanced stress-resistance were dependent on this transcription factor. DAF-16 (homolog to mammalian FOXO) is another pivotal aging-related transcription factor in the nematode. We demonstrate that DAF-16 does not participate in the beneficial effects of baicalein: since baicalein causes no increase in the nuclear translocation of DAF-16 (DAF-16::GFP expressing strain, incubation time: 1h) and it still induces longevity even in a DAF-16 loss-of-function strain, we conclude, that baicalein increases stress-resistance and life span in C. elegans via SKN-1 but not DAF-16. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Porcine Knock-in Fibroblasts Expressing hDAF on α-1,3-Galactosyltransferase (GGTA1) Gene Locus.

    Science.gov (United States)

    Kim, Ji Woo; Kim, Hye-Min; Lee, Sang Mi; Kang, Man-Jong

    2012-10-01

    The Galactose-α1,3-galactose (α1,3Gal) epitope is responsible for hyperacute rejection in pig-to-human xenotransplantation. Human decay-accelerating factor (hDAF) is a cell surface regulatory protein that serves as a complement inhibitor to protect self cells from complement attack. The generation of α1,3-galactosyltransferase (GGTA1) knock-out pigs expressing DAF is a necessary step for their use as organ donors for humans. In this study, we established GGTA1 knock-out cell lines expressing DAF from pig ear fibroblasts for somatic cell nuclear transfer. hDAF expression was detected in hDAF knock-in heterozygous cells, but not in normal pig cells. Expression of the GGTA1 gene was lower in the knock-in heterozygous cell line compared to the normal pig cell. Knock-in heterozygous cells afforded more effective protection against cytotoxicity with human serum than with GGTA1 knock-out heterozygous and control cells. These cell lines may be used in the production of GGTA1 knock-out and DAF expression pigs for xenotransplantation.

  17. The Deubiquitylase MATH-33 Controls DAF-16 Stability and Function in Metabolism and Longevity

    NARCIS (Netherlands)

    Heimbucher, Thomas; Liu, Zheng; Bossard, Carine; McCloskey, Richard; Carrano, Andrea C.; Riedel, Christian G.; Tanasa, Bogdan; Klammt, Christian; Fonslow, Bryan R.; Riera, Celine E.; Lillemeier, Bjorn F.; Kemphues, Kenneth; Yates, John R.; O'Shea, Clodagh; Hunter, Tony; Dillin, Andrew

    2015-01-01

    FOXO family transcription factors are downstream effectors of Insulin/IGF-1 signaling (IIS) and major determinants of aging in organisms ranging from worms to man. The molecular mechanisms that actively promote DAF16/FOXO stability and function are unknown. Here we identify the deubiquitylating

  18. Functional Conservation and Divergence of daf-22 Paralogs in Pristionchus pacificus Dauer Development.

    Science.gov (United States)

    Markov, Gabriel V; Meyer, Jan M; Panda, Oishika; Artyukhin, Alexander B; Claaßen, Marc; Witte, Hanh; Schroeder, Frank C; Sommer, Ralf J

    2016-10-01

    Small-molecule signaling in nematode dauer formation has emerged as a major model to study chemical communication in development and evolution. Developmental arrest as nonfeeding and stress-resistant dauer larvae represents the major survival and dispersal strategy. Detailed studies in Caenorhabditis elegans and Pristionchus pacificus revealed that small-molecule communication changes rapidly in evolution resulting in extreme structural diversity of small-molecule compounds. In C. elegans, a blend of ascarosides constitutes the dauer pheromone, whereas the P. pacificus dauer pheromone includes additional paratosides and integrates building blocks from diverse primary metabolic pathways. Despite this complexity of small-molecule structures and functions, little is known about the biosynthesis of small molecules in nematodes outside C. elegans Here, we show that the genes encoding enzymes of the peroxisomal β-oxidation pathway involved in small-molecule biosynthesis evolve rapidly, including gene duplications and domain switching. The thiolase daf-22, the most downstream factor in C. elegans peroxisomal β-oxidation, has duplicated in P. pacificus, resulting in Ppa-daf-22.1, which still contains the sterol-carrier-protein (SCP) domain that was lost in C. elegans daf-22, and Ppa-daf-22.2. Using the CRISPR/Cas9 system, we induced mutations in both P. pacificus daf-22 genes and identified an unexpected complexity of functional conservation and divergence. Under well-fed conditions, ascaroside biosynthesis proceeds exclusively via Ppa-daf-22.1 In contrast, starvation conditions induce Ppa-daf-22.2 activity, resulting in the production of a specific subset of ascarosides. Gene expression studies indicate a reciprocal up-regulation of both Ppa-daf-22 genes, which is, however, independent of starvation. Thus, our study reveals an unexpected functional complexity of dauer development and evolution. © The Author 2016. Published by Oxford University Press on behalf of the

  19. Piceatannol extends the lifespan of Caenorhabditis elegans via DAF-16.

    Science.gov (United States)

    Shen, Peiyi; Yue, Yiren; Sun, Quancai; Kasireddy, Nandita; Kim, Kee-Hong; Park, Yeonhwa

    2017-05-06

    Piceatannol is a natural stilbene with many beneficial effects, such as antioxidative, anti-inflammatory, antiatherogenic activities; however, its role on aging is not known. In this study, we used Caenorhabditis elegans as an animal model to study the effect of piceatannol on its lifespan and investigated the underlying mechanisms. The results showed that 50 and 100 µM piceatannol significantly extended the lifespan of C. elegans without altering the growth rate, worm size and progeny production. Piceatannol delayed the age-related decline of pumping rate and locomotive activity, and protected the worms from heat and oxidative stress. This study further indicated that lifespan extension and enhanced stress resistance induced by piceatannol requires DAF-16. Since DAF-16 is conserved from nematodes to mammals, our study may have important implications in utilizing piceatannol to promote healthy aging and combat age-related disease in humans. © 2016 BioFactors, 43(3):379-387, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

  20. Relative Contribution of Cellular Complement Inhibitors CD59, CD46, and CD55 to Parainfluenza Virus 5 Inhibition of Complement-Mediated Neutralization

    Directory of Open Access Journals (Sweden)

    Yujia Li

    2018-04-01

    Full Text Available The complement system is a part of the innate immune system that viruses need to face during infections. Many viruses incorporate cellular regulators of complement activation (RCA to block complement pathways and our prior work has shown that Parainfluenza virus 5 (PIV5 incorporates CD55 and CD46 to delay complement-mediated neutralization. In this paper, we tested the role of a third individual RCA inhibitor CD59 in PIV5 interactions with complement pathways. Using a cell line engineered to express CD59, we show that small levels of functional CD59 are associated with progeny PIV5, which is capable of blocking assembly of the C5b-C9 membrane attack complex (MAC. PIV5 containing CD59 (PIV5-CD59 showed increased resistance to complement-mediated neutralization in vitro comparing to PIV5 lacking regulators. Infection of A549 cells with PIV5 and RSV upregulated CD59 expression. TGF-beta treatment of PIV5-infected cells also increased cell surface CD59 expression and progeny virions were more resistant to complement-mediated neutralization. A comparison of individual viruses containing only CD55, CD46, or CD59 showed a potency of inhibiting complement-mediated neutralization, which followed a pattern of CD55 > CD46 > CD59.

  1. Immunohistochemical Expression and Prognostic Significance of CD97 and its Ligand DAF in Human Cervical Squamous Cell Carcinoma.

    Science.gov (United States)

    He, Ying; Wang, Wei; Xu, Lian; Li, Li; Liu, Juan; Feng, Min; Bu, Hong

    2015-09-01

    Accumulating evidences had demonstrated that the CD97, a member of the epidermal growth factor 7-transmembrane family, and its cellular ligand decay accelerating factor (DAF) both play important roles in tumor dedifferentiation, migration, invasiveness, and metastasis. However, the roles of CD97 and DAF in human cervical squamous cell carcinoma (CSCC) have not been investigated. The purpose of this study was to observe the expression profile of CD97 and DAF in CSCC and evaluate their clinical significance. Immunohistochemistry was used to investigate the expression of CD97 and DAF proteins in 97 patients with CSCC and 53 patients with cervical intraepithelial neoplasia, a precursor lesion of CSCC. CD97 and DAF were absent or only weakly expressed in the normal epithelium of the cervix but were present in 83.5% (81/97) and 90.7% (88/97) of CSCC samples, respectively. Overexpression of CD97 was significantly associated with a high International Federation of Gynecology and Obstetrics stage (P=0.010) and lymph node metastasis (P=0.026). The majority of CSCCs, irrespective of staging/grading classification, displayed strong DAF immunostaining. Kaplan-Meier survival analysis revealed that overexpression of CD97 was associated with a worse prognosis. Multivariate analyses showed that the International Federation of Gynecology and Obstetrics stage (P=0.000), lymph node metastasis (P=0.004), and CD97 expression (P=0.040) were independent risk factors for overall survival. The present study suggested that the expressions of CD97 and DAF were both upregulated in CSCC. The expression level of CD97 in CSCC was associated with the severity of the tumor. Furthermore, CD97 might be an independent poor prognostic factor for CSCC patients.

  2. Effects of Caenorhabditis elegans sgk-1 mutations on lifespan, stress resistance, and DAF-16/FoxO regulation.

    Science.gov (United States)

    Chen, Albert Tzong-Yang; Guo, Chunfang; Dumas, Kathleen J; Ashrafi, Kaveh; Hu, Patrick J

    2013-10-01

    The AGC family serine-threonine kinases Akt and Sgk are similar in primary amino acid sequence and in vitro substrate specificity, and both kinases are thought to directly phosphorylate and inhibit FoxO transcription factors. In the nematode Caenorhabditis elegans, it is well established that AKT-1 controls dauer arrest and lifespan by regulating the subcellular localization of the FoxO transcription factor DAF-16. SGK-1 is thought to act similarly to AKT-1 in lifespan control by phosphorylating and inhibiting the nuclear translocation of DAF-16/FoxO. Using sgk-1 null and gain-of-function mutants, we now provide multiple lines of evidence indicating that AKT-1 and SGK-1 influence C. elegans lifespan, stress resistance, and DAF-16/FoxO activity in fundamentally different ways. Whereas AKT-1 shortens lifespan, SGK-1 promotes longevity in a DAF-16-/FoxO-dependent manner. In contrast to AKT-1, which reduces resistance to multiple stresses, SGK-1 promotes resistance to oxidative stress and ultraviolet radiation but inhibits thermotolerance. Analysis of several DAF-16/FoxO target genes that are repressed by AKT-1 reveals that SGK-1 represses a subset of these genes while having little influence on the expression of others. Accordingly, unlike AKT-1, which promotes the cytoplasmic sequestration of DAF-16/FoxO, SGK-1 does not influence DAF-16/FoxO subcellular localization. Thus, in spite of their similar in vitro substrate specificities, Akt and Sgk influence longevity, stress resistance, and FoxO activity through distinct mechanisms in vivo. Our findings highlight the need for a re-evaluation of current paradigms of FoxO regulation by Sgk. © 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  3. Myricetin-Mediated Lifespan Extension in Caenorhabditis elegans Is Modulated by DAF-16

    Directory of Open Access Journals (Sweden)

    Wim Wätjen

    2013-06-01

    Full Text Available Myricetin is a naturally occurring flavonol found in many plant based food sources. It increases the lifespan of Caenorhabditis elegans, but the molecular mechanisms are not yet fully understood. We have investigated the impact of this flavonoid on the transcription factors DAF-16 (C. elegans FoxO homologue and SKN-1 (Nrf2 homologue, which have crucial functions in the regulation of ageing. Myricetin is rapidly assimilated by the nematode, causes a nuclear translocation of DAF-16 but not of SKN-1, and finally prolongs the mean adult lifespan of C. elegans by 32.9%. The lifespan prolongation was associated with a decrease in the accumulation of reactive oxygen species (ROS detected by DCF. Myricetin also decreases the formation of lipofuscin, a pigment consisting of highly oxidized and cross-linked proteins that is considered as a biomarker of ageing in diverse species. The lifespan extension was completely abolished in a daf-16 loss-of-function mutant strain (CF1038. Consistently with this result, myricetin was also not able to diminish stress-induced ROS accumulation in the mutant. These results strongly indicate that the pro-longevity effect of myricetin is dependent on DAF-16 and not on direct anti-oxidative effects of the flavonoid.

  4. C. elegans DAF-16/FOXO interacts with TGF-ß/BMP signaling to induce germline tumor formation via mTORC1 activation.

    Directory of Open Access Journals (Sweden)

    Wenjing Qi

    2017-05-01

    Full Text Available Activation of the FOXO transcription factor DAF-16 by reduced insulin/IGF signaling (IIS is considered to be beneficial in C. elegans due to its ability to extend lifespan and to enhance stress resistance. In the germline, cell-autonomous DAF-16 activity prevents stem cell proliferation, thus acting tumor-suppressive. In contrast, hypodermal DAF-16 causes a tumorous germline phenotype characterized by hyperproliferation of the germline stem cells and rupture of the adjacent basement membrane. Here we show that cross-talk between DAF-16 and the transforming growth factor ß (TGFß/bone morphogenic protein (BMP signaling pathway causes germline hyperplasia and results in disruption of the basement membrane. In addition to activating MADM/NRBP/hpo-11 gene alone, DAF-16 also directly interacts with both R-SMAD proteins SMA-2 and SMA-3 in the nucleus to regulate the expression of mTORC1 pathway. Knocking-down of BMP genes or each of the four target genes in the hypodermis was sufficient to inhibit germline proliferation, indicating a cell-non-autonomously controlled regulation of stem cell proliferation by somatic tissues. We propose the existence of two antagonistic DAF-16/FOXO functions, a cell-proliferative somatic and an anti-proliferative germline activity. Whereas germline hyperplasia under reduced IIS is inhibited by DAF-16 cell-autonomously, activation of somatic DAF-16 in the presence of active IIS promotes germline proliferation and eventually induces tumor-like germline growth. In summary, our results suggest a novel pathway crosstalk of DAF-16 and TGF-ß/BMP that can modulate mTORC1 at the transcriptional level to cause stem-cell hyperproliferation. Such cell-type specific differences may help explaining why human FOXO activity is considered to be tumor-suppressive in most contexts, but may become oncogenic, e.g. in chronic and acute myeloid leukemia.

  5. C. elegans DAF-16/FOXO interacts with TGF-ß/BMP signaling to induce germline tumor formation via mTORC1 activation.

    Science.gov (United States)

    Qi, Wenjing; Yan, Yijian; Pfeifer, Dietmar; Donner V Gromoff, Erika; Wang, Yimin; Maier, Wolfgang; Baumeister, Ralf

    2017-05-01

    Activation of the FOXO transcription factor DAF-16 by reduced insulin/IGF signaling (IIS) is considered to be beneficial in C. elegans due to its ability to extend lifespan and to enhance stress resistance. In the germline, cell-autonomous DAF-16 activity prevents stem cell proliferation, thus acting tumor-suppressive. In contrast, hypodermal DAF-16 causes a tumorous germline phenotype characterized by hyperproliferation of the germline stem cells and rupture of the adjacent basement membrane. Here we show that cross-talk between DAF-16 and the transforming growth factor ß (TGFß)/bone morphogenic protein (BMP) signaling pathway causes germline hyperplasia and results in disruption of the basement membrane. In addition to activating MADM/NRBP/hpo-11 gene alone, DAF-16 also directly interacts with both R-SMAD proteins SMA-2 and SMA-3 in the nucleus to regulate the expression of mTORC1 pathway. Knocking-down of BMP genes or each of the four target genes in the hypodermis was sufficient to inhibit germline proliferation, indicating a cell-non-autonomously controlled regulation of stem cell proliferation by somatic tissues. We propose the existence of two antagonistic DAF-16/FOXO functions, a cell-proliferative somatic and an anti-proliferative germline activity. Whereas germline hyperplasia under reduced IIS is inhibited by DAF-16 cell-autonomously, activation of somatic DAF-16 in the presence of active IIS promotes germline proliferation and eventually induces tumor-like germline growth. In summary, our results suggest a novel pathway crosstalk of DAF-16 and TGF-ß/BMP that can modulate mTORC1 at the transcriptional level to cause stem-cell hyperproliferation. Such cell-type specific differences may help explaining why human FOXO activity is considered to be tumor-suppressive in most contexts, but may become oncogenic, e.g. in chronic and acute myeloid leukemia.

  6. Localization of Nitric Oxide in Wheat Roots by DAF Fluorescence.

    Science.gov (United States)

    Wany, Aakanksha; Gupta, Kapuganti Jagadis

    2016-01-01

    Nitric oxide is a free radical signal molecule. Various methods are available for measurement of NO. Out of all methods, fluorescent probes to localize NO is very widely used method. Diaminofluorescein in diacetate form (DAF-2DA) is most widely probe for NO measurement. This method is based on application of 4,5-diaminofluorescein diacetate (DAF-2DA) which is actively diffused into cells, once taken up by cells cytoplasmic esterases cleave the acetate groups to generate 4,5-diaminofluorescein; DAF-2. The generated DAF-2 can readily react with N2O3, which is an oxidation product of NO to generate the highly fluorescent DAF-2T (triazolofluorescein). There are various advantages and disadvantages associated with this method, but to its advantage in diffusion closely to NO producing sites, it is widely used for localization studies. Here, we describe method to make sections of the roots and localization of NO in roots subjected to hypoxic stress.

  7. Germline signaling mediates the synergistically prolonged longevity produced by double mutations in daf-2 and rsks-1 in C. elegans.

    Science.gov (United States)

    Chen, Di; Li, Patrick Wai-Lun; Goldstein, Benjamin A; Cai, Waijiao; Thomas, Emma Lynn; Chen, Fen; Hubbard, Alan E; Melov, Simon; Kapahi, Pankaj

    2013-12-26

    Inhibition of DAF-2 (insulin-like growth factor 1 [IGF-1] receptor) or RSKS-1 (S6K), key molecules in the insulin/IGF-1 signaling (IIS) and target of rapamycin (TOR) pathways, respectively, extend lifespan in Caenorhabditis elegans. However, it has not been clear how and in which tissues they interact with each other to modulate longevity. Here, we demonstrate that a combination of mutations in daf-2 and rsks-1 produces a nearly 5-fold increase in longevity that is much greater than the sum of single mutations. This synergistic lifespan extension requires positive feedback regulation of DAF-16 (FOXO) via the AMP-activated protein kinase (AMPK) complex. Furthermore, we identify germline as the key tissue for this synergistic longevity. Moreover, germline-specific inhibition of rsks-1 activates DAF-16 in the intestine. Together, our findings highlight the importance of the germline in the significantly increased longevity produced by daf-2 rsks-1, which has important implications for interactions between the two major conserved longevity pathways in more complex organisms. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  8. The influence of floc size and hydraulic detention time on the performance of a dissolved air flotation (DAF) pilot unit in the light of a mathematical model.

    Science.gov (United States)

    Moruzzi, R B; Reali, M A P

    2014-12-01

    The influence of floc size and hydraulic detention time on the performance of a dissolved air flotation (DAF) pilot unit was investigated in the light of a known mathematical model. The following design and operational parameters were considered: the hydraulic detention time (tdcz) and hydraulic loading rate in the contact zone, the down-flow loading rate in the clarification zone, the particle size distribution (d F), and the recirculation rate (p). As a reference for DAF performance analysis, the proposed β.td parameter from the above mentioned mathematical model was employed. The results indicated that tdcz is an important factor in DAF performance and that d F and floc size are also determinants of DAF efficiency. Further, β.td was sensitive to both design and operational parameters, which were varied in the DAF pilot plant. The performance of the DAF unit decreases with increasing β.td values because a higher td (considering a fixed β) or a higher β (e.g., higher hydrophobicity of the flocs for a fixed td) would be necessary in the reaction zone to reach desired flotation efficiency.

  9. Activation of DAF-16/FOXO by reactive oxygen species contributes to longevity in long-lived mitochondrial mutants in Caenorhabditis elegans.

    Science.gov (United States)

    Senchuk, Megan M; Dues, Dylan J; Schaar, Claire E; Johnson, Benjamin K; Madaj, Zachary B; Bowman, Megan J; Winn, Mary E; Van Raamsdonk, Jeremy M

    2018-03-01

    Mild deficits in mitochondrial function have been shown to increase lifespan in multiple species including worms, flies and mice. Here, we study three C. elegans mitochondrial mutants (clk-1, isp-1 and nuo-6) to identify overlapping genetic pathways that contribute to their longevity. We find that genes regulated by the FOXO transcription factor DAF-16 are upregulated in all three strains, and that the transcriptional changes present in these worms overlap significantly with the long-lived insulin-IGF1 signaling pathway mutant daf-2. We show that DAF-16 and multiple DAF-16 interacting proteins (MATH-33, IMB-2, CST-1/2, BAR-1) are required for the full longevity of all three mitochondrial mutants. Our results suggest that the activation of DAF-16 in these mutants results from elevated levels of reactive oxygen species. Overall, this work reveals an overlapping genetic pathway required for longevity in three mitochondrial mutants, and, combined with previous work, demonstrates that DAF-16 is a downstream mediator of lifespan extension in multiple pathways of longevity.

  10. Role of DAF-21protein in Caenorhabditis elegans immunity against Proteus mirabilis infection.

    Science.gov (United States)

    JebaMercy, Gnanasekaran; Durai, Sellegounder; Prithika, Udayakumar; Marudhupandiyan, Shanmugam; Dasauni, Pushpanjali; Kundu, Suman; Balamurugan, Krishnaswamy

    2016-08-11

    Caenorhabditis elegans is emerging as one of the handy model for proteome related studies due to its simplest system biology. The present study, deals with changes in protein expression in C. elegans infected with Proteus mirabilis. Proteins were separated using two-dimensional differential gel electrophoresis (2D-DIGE) and identified using MALDI-TOF. Twelve distinctly regulated proteins identified in the infected worms, included heat shock proteins involved stress pathway (HSP-1 and HSP-6), proteins involved in immune response pathway (DAF-21), enzymes involved in normal cellular process (Eukaryotic translation Elongation Factor, actin family member, S-adenosyl homocysteine hydrolase ortholog, glutamate dehydrogenase and Vacuolar H ATPase family member) and few least characterized proteins (H28O16.1 and H08J11.2). The regulation of selected players at the transcriptional level during Proteus mirabilis infection was analyzed using qPCR. Physiological experiments revealed the ability of P. mirabilis to kill daf-21 mutant C. elegans significantly compared with the wild type. This is the first report studying proteome changes in C. elegans and exploring the involvement of MAP Kinase pathway during P. mirabilis infection. This is the first report studying proteome changes in C. elegans during P. mirabilis infection. The present study explores the role and contribution of MAP Kinase pathway and its regulator protein DAF-21 involvement in the immunity against opportunistic pathogen P. mirabilis infection. Manipulation of this DAF-21 protein in host, may pave the way for new drug development or disease control strategy during opportunistic pathogen infections. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Application of the pothole DAF method to vehicles traversing periodic roadway irregularities

    Science.gov (United States)

    Pesterev, A. V.; Bergman, L. A.; Tan, C. A.; Yang, B.

    2005-01-01

    This paper is a sequel to the work discussed in Pesterev et al. (Journal of Sound and Vibration, in press). In that paper, it was suggested that the technique to determine the effect of a local road surface irregularity on the dynamics of a vehicle modelled as a linear multi-degree-of-freedom system relies on the so-called pothole dynamic amplification factor (DAF), which is a complex-valued function specific to the irregularity shape. This paper discusses the companion problem of how to determine the DAF function for an irregularity represented as a superposition of simpler ones. Another purpose of this paper is to demonstrate the application of the pothole DAF functions technique to finding a priori estimates of the effect of irregularities with a repeated structure. Specifically, we solve the problem of finding the conditions under which the dynamic effect of two identical potholes located one after another is greater than that due to the single pothole. We also find the estimate for the number of periods of a periodic irregularity that are sufficient in order to consider the oscillator response as steady state. The discussions are illustrated by numerical examples.

  12. Catalpol Modulates Lifespan via DAF-16/FOXO and SKN-1/Nrf2 Activation in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Hyun Won Seo

    2015-01-01

    Full Text Available Catalpol is an effective component of rehmannia root and known to possess various pharmacological properties. The present study was aimed at investigating the potential effects of catalpol on the lifespan and stress tolerance using C. elegans model system. Herein, catalpol showed potent lifespan extension of wild-type nematode under normal culture condition. In addition, survival rate of catalpol-fed nematodes was significantly elevated compared to untreated control under heat and oxidative stress but not under hyperosmolality conditions. We also found that elevated antioxidant enzyme activities and expressions of stress resistance proteins were attributed to catalpol-mediated increased stress tolerance of nematode. We further investigated whether catalpol’s longevity effect is related to aging-related factors including reproduction, food intake, and growth. Interestingly, catalpol exposure could attenuate pharyngeal pumping rate, indicating that catalpol may induce dietary restriction of nematode. Moreover, locomotory ability of aged nematode was significantly improved by catalpol treatment, while lipofuscin levels were attenuated, suggesting that catalpol may affect age-associated changes of nematode. Our mechanistic studies revealed that mek-1, daf-2, age-1, daf-16, and skn-1 are involved in catalpol-mediated longevity. These results indicate that catalpol extends lifespan and increases stress tolerance of C. elegans via DAF-16/FOXO and SKN-1/Nrf activation dependent on insulin/IGF signaling and JNK signaling.

  13. Acoustic sensitivity of the saccule and daf music.

    Science.gov (United States)

    Emami, Seyede Faranak

    2014-04-01

    The daf is a large Persian frame drum used as a musical instrument in both popular and classical music which can induce a percussive sound at low frequencies (146-290 Hz) with peaks of up to 130 dBspl. The percussive sounds have a power distribution in the region of saccular sensitivity. In view of the saccular stimulation by sound in humans, we decided to use cervical vestibular-evoked myogenic potentials (cVEMPs) to evaluate the possibility that the daf music may have a disturbing effect on saccular function. During this case-control study, 18 daf musicians were compared with 20 healthy individuals evaluated in the audiology department of the Hamadan University of Medical Sciences. Assessment consisted of pure tone audiometry, tympanometry, and cVEMPs. Multiple comparisons of mean the cVEMPs and mean hearing loss at 250 Hz among the three groups (affected, unaffected, and normal ears) were significant. There were no significant differences between all daf players on high-tone loss at 3000 Hz. The daf musicians had bilateral unsymmetrical sensorineural hearing loss (SNHL), with hearing loss at 250 Hz (low-tone loss) and notched audiogram at 3000 Hz (high-tone loss). Eleven musicians with decreased vestibular excitability as detected by abnormal cVEMPs had mild (26-40 dBHL) low-tone loss and significant abnormal cVEMPs findings. In contrast, the others had slight (16-25 dBHL) low-tone loss with normal cVEMPs. Exposure to daf music is related to both saccular and cochlear dysfunction. Exposure to daf music is related to both saccular and cochlear dysfunction.

  14. PMK-1 p38 MAPK promotes cadmium stress resistance, the expression of SKN-1/Nrf and DAF-16 target genes, and protein biosynthesis in Caenorhabditis elegans.

    Science.gov (United States)

    Keshet, Alex; Mertenskötter, Ansgar; Winter, Sarah A; Brinkmann, Vanessa; Dölling, Ramona; Paul, Rüdiger J

    2017-12-01

    The mechanisms of cadmium (Cd) resistance are complex and not sufficiently understood. The present study, therefore, aimed at assessing the roles of important components of stress-signaling pathways and of ABC transporters under severe Cd stress in Caenorhabditis elegans. Survival assays on mutant and control animals revealed a significant promotion of Cd resistance by the PMK-1 p38 MAP kinase, the transcription factor DAF-16/FoxO, and the ABC transporter MRP-1. Transcriptome profiling by RNA-Seq on wild type and a pmk-1 mutant under control and Cd stress conditions revealed, inter alia, a PMK-1-dependent promotion of gene expression for the translational machinery. PMK-1 also promoted the expression of target genes of the transcription factors SKN-1/Nrf and DAF-16 in Cd-stressed animals, which included genes for molecular chaperones or immune proteins. Gene expression studies by qRT-PCR confirmed the positive effects of PMK-1 on DAF-16 activity under Cd stress and revealed negative effects of DAF-16 on the expression of genes for MRP-1 and DAF-15/raptor. Additional studies on pmk-1 RNAi-treated wild type and mutant strains provided further information on the effects of PMK-1 on SKN-1 and DAF-16, which resulted in a model of these relationships. The results of this study demonstrate a central role of PMK-1 for the processing of cellular responses to abiotic and biotic stressors, with the promoting effects of PMK-1 on Cd resistance mostly mediated by the transcription factors SKN-1 and DAF-16.

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

    Science.gov (United States)

    Kim, Yongsoon; Sun, Hong

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yongsoon Kim

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

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

    Science.gov (United States)

    Kim, Yongsoon; Sun, Hong

    2012-01-01

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

  18. DAF-16/FoxO directly regulates an atypical AMP-activated protein kinase gamma isoform to mediate the effects of insulin/IGF-1 signaling on aging in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Jennifer M A Tullet

    2014-02-01

    Full Text Available The DAF-16/FoxO transcription factor controls growth, metabolism and aging in Caenorhabditis elegans. The large number of genes that it regulates has been an obstacle to understanding its function. However, recent analysis of transcript and chromatin profiling implies that DAF-16 regulates relatively few genes directly, and that many of these encode other regulatory proteins. We have investigated the regulation by DAF-16 of genes encoding the AMP-activated protein kinase (AMPK, which has α, β and γ subunits. C. elegans has 5 genes encoding putative AMP-binding regulatory γ subunits, aakg-1-5. aakg-4 and aakg-5 are closely related, atypical isoforms, with orthologs throughout the Chromadorea class of nematodes. We report that ∼75% of total γ subunit mRNA encodes these 2 divergent isoforms, which lack consensus AMP-binding residues, suggesting AMP-independent kinase activity. DAF-16 directly activates expression of aakg-4, reduction of which suppresses longevity in daf-2 insulin/IGF-1 receptor mutants. This implies that an increase in the activity of AMPK containing the AAKG-4 γ subunit caused by direct activation by DAF-16 slows aging in daf-2 mutants. Knock down of aakg-4 expression caused a transient decrease in activation of expression in multiple DAF-16 target genes. This, taken together with previous evidence that AMPK promotes DAF-16 activity, implies the action of these two metabolic regulators in a positive feedback loop that accelerates the induction of DAF-16 target gene expression. The AMPK β subunit, aakb-1, also proved to be up-regulated by DAF-16, but had no effect on lifespan. These findings reveal key features of the architecture of the gene-regulatory network centered on DAF-16, and raise the possibility that activation of AMP-independent AMPK in nutritionally replete daf-2 mutant adults slows aging in C. elegans. Evidence of activation of AMPK subunits in mammals suggests that such FoxO-AMPK interactions may be

  19. DAF-16/FoxO directly regulates an atypical AMP-activated protein kinase gamma isoform to mediate the effects of insulin/IGF-1 signaling on aging in Caenorhabditis elegans.

    Science.gov (United States)

    Tullet, Jennifer M A; Araiz, Caroline; Sanders, Matthew J; Au, Catherine; Benedetto, Alexandre; Papatheodorou, Irene; Clark, Emily; Schmeisser, Kathrin; Jones, Daniel; Schuster, Eugene F; Thornton, Janet M; Gems, David

    2014-02-01

    The DAF-16/FoxO transcription factor controls growth, metabolism and aging in Caenorhabditis elegans. The large number of genes that it regulates has been an obstacle to understanding its function. However, recent analysis of transcript and chromatin profiling implies that DAF-16 regulates relatively few genes directly, and that many of these encode other regulatory proteins. We have investigated the regulation by DAF-16 of genes encoding the AMP-activated protein kinase (AMPK), which has α, β and γ subunits. C. elegans has 5 genes encoding putative AMP-binding regulatory γ subunits, aakg-1-5. aakg-4 and aakg-5 are closely related, atypical isoforms, with orthologs throughout the Chromadorea class of nematodes. We report that ∼75% of total γ subunit mRNA encodes these 2 divergent isoforms, which lack consensus AMP-binding residues, suggesting AMP-independent kinase activity. DAF-16 directly activates expression of aakg-4, reduction of which suppresses longevity in daf-2 insulin/IGF-1 receptor mutants. This implies that an increase in the activity of AMPK containing the AAKG-4 γ subunit caused by direct activation by DAF-16 slows aging in daf-2 mutants. Knock down of aakg-4 expression caused a transient decrease in activation of expression in multiple DAF-16 target genes. This, taken together with previous evidence that AMPK promotes DAF-16 activity, implies the action of these two metabolic regulators in a positive feedback loop that accelerates the induction of DAF-16 target gene expression. The AMPK β subunit, aakb-1, also proved to be up-regulated by DAF-16, but had no effect on lifespan. These findings reveal key features of the architecture of the gene-regulatory network centered on DAF-16, and raise the possibility that activation of AMP-independent AMPK in nutritionally replete daf-2 mutant adults slows aging in C. elegans. Evidence of activation of AMPK subunits in mammals suggests that such FoxO-AMPK interactions may be evolutionarily conserved.

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  12. Lowbush cranberry acts through DAF-16/FOXO signaling to promote increased lifespan and axon branching in aging posterior touch receptor neurons.

    Science.gov (United States)

    Scerbak, Courtney; Vayndorf, Elena; Hernandez, Alicia; McGill, Colin; Taylor, Barbara

    2018-05-01

    Medicinal berries are appreciated for their health benefits, in traditional ecological knowledge and nutrition science. Determining the cellular mechanisms underlying the effects of berry supplementation may contribute to our understanding of aging. Here, we report that lowbush cranberry (Vaccinium vitis-idaea) treatment causes marked nuclear localization of the central aging-related transcription factor DAF-16/FOXO in aged Caenorhabditis elegans. Further, functional DAF-16 is required for the lifespan extension, improved mechanosensation, and posterior touch receptor neuron morphological changes induced by lowbush cranberry treatments. DAF-16 is not observed in nuceli nor required for lifespan extension in lifespan-extending Alaskan blueberry treatments and, while DAF-16 is not visibly induced into the nucleus in lifespan-extending Alaskan chaga treatments, it is required for chaga-induced lifespan extension. These findings underscore the importance of DAF-16 in the aging of whole organisms and touch receptor neurons and also, importantly, indicate that this critical pathway is not always activated upon consumption of functional foods that impact aging.

  13. RNA surveillance via nonsense-mediated mRNA decay is crucial for longevity in daf-2/insulin/IGF-1 mutant C. elegans.

    Science.gov (United States)

    Son, Heehwa G; Seo, Mihwa; Ham, Seokjin; Hwang, Wooseon; Lee, Dongyeop; An, Seon Woo A; Artan, Murat; Seo, Keunhee; Kaletsky, Rachel; Arey, Rachel N; Ryu, Youngjae; Ha, Chang Man; Kim, Yoon Ki; Murphy, Coleen T; Roh, Tae-Young; Nam, Hong Gil; Lee, Seung-Jae V

    2017-03-09

    Long-lived organisms often feature more stringent protein and DNA quality control. However, whether RNA quality control mechanisms, such as nonsense-mediated mRNA decay (NMD), which degrades both abnormal as well as some normal transcripts, have a role in organismal aging remains unexplored. Here we show that NMD mediates longevity in C. elegans strains with mutations in daf-2/insulin/insulin-like growth factor 1 receptor. We find that daf-2 mutants display enhanced NMD activity and reduced levels of potentially aberrant transcripts. NMD components, including smg-2/UPF1, are required to achieve the longevity of several long-lived mutants, including daf-2 mutant worms. NMD in the nervous system of the animals is particularly important for RNA quality control to promote longevity. Furthermore, we find that downregulation of yars-2/tyrosyl-tRNA synthetase, an NMD target transcript, by daf-2 mutations contributes to longevity. We propose that NMD-mediated RNA surveillance is a crucial quality control process that contributes to longevity conferred by daf-2 mutations.

  14. Identification of ligands for DAF-12 that govern dauer formation and reproduction in C. elegans.

    Science.gov (United States)

    Motola, Daniel L; Cummins, Carolyn L; Rottiers, Veerle; Sharma, Kamalesh K; Li, Tingting; Li, Yong; Suino-Powell, Kelly; Xu, H Eric; Auchus, Richard J; Antebi, Adam; Mangelsdorf, David J

    2006-03-24

    In response to environmental and dietary cues, the C. elegans orphan nuclear receptor, DAF-12, regulates dauer diapause, reproductive development, fat metabolism, and life span. Despite strong evidence for hormonal control, the identification of the DAF-12 ligand has remained elusive. In this work, we identified two distinct 3-keto-cholestenoic acid metabolites of DAF-9, a cytochrome P450 involved in hormone production, that function as ligands for DAF-12. At nanomolar concentrations, these steroidal ligands (called dafachronic acids) bind and transactivate DAF-12 and rescue the hormone deficiency of daf-9 mutants. Interestingly, DAF-9 has a biochemical activity similar to mammalian CYP27A1 catalyzing addition of a terminal acid to the side chain of sterol metabolites. Together, these results define the first steroid hormones in nematodes as ligands for an invertebrate orphan nuclear receptor and demonstrate that steroidal regulation of reproduction, from biology to molecular mechanism, is conserved from worms to humans.

  15. Activated AKT/PKB signaling in C. elegans uncouples temporally distinct outputs of DAF-2/insulin-like signaling

    Directory of Open Access Journals (Sweden)

    Hanselman Keaton B

    2006-10-01

    Full Text Available Abstract Background In the nematode, Caenorhabditis elegans, a conserved insulin-like signaling pathway controls larval development, stress resistance and adult lifespan. AGE-1, a homolog of the p110 catalytic subunit of phosphoinositide 3-kinases (PI3K comprises the major known effector pathway downstream of the insulin receptor, DAF-2. Phospholipid products of AGE-1/PI3K activate AKT/PKB kinase signaling via PDK-1. AKT/PKB signaling antagonizes nuclear translocation of the DAF-16/FOXO transcription factor. Reduced AGE-1/PI3K signaling permits DAF-16 to direct dauer larval arrest and promote long lifespan in adult animals. In order to study the downstream effectors of AGE-1/PI3K signaling in C. elegans, we conducted a genetic screen for mutations that suppress the constitutive dauer arrest phenotype of age-1(mg109 animals. Results This report describes mutations recovered in a screen for suppressors of the constitutive dauer arrest (daf-C phenotype of age-1(mg109. Two mutations corresponded to alleles of daf-16. Two mutations were gain-of-function alleles in the genes, akt-1 and pdk-1, encoding phosphoinositide-dependent serine/threonine kinases. A fifth mutation, mg227, located on chromosome X, did not correspond to any known dauer genes, suggesting that mg227 may represent a new component of the insulin pathway. Genetic epistasis analysis by RNAi showed that reproductive development in age-1(mg109;akt-1(mg247 animals was dependent on the presence of pdk-1. Similarly, reproductive development in age-1(mg109;pdk-1(mg261 animals was dependent on akt-1. However, reproductive development in age-1(mg109; mg227 animals required only akt-1, and pdk-1 activity was dispensable in this background. Interestingly, while mg227 suppressed dauer arrest in age-1(mg109 animals, it enhanced the long lifespan phenotype. In contrast, akt-1(mg247 and pdk-1(mg261 did not affect lifespan or stress resistance, while both daf-16 alleles fully suppressed these

  16. Activated AKT/PKB signaling in C. elegans uncouples temporally distinct outputs of DAF-2/insulin-like signaling.

    Science.gov (United States)

    Gami, Minaxi S; Iser, Wendy B; Hanselman, Keaton B; Wolkow, Catherine A

    2006-10-04

    In the nematode, Caenorhabditis elegans, a conserved insulin-like signaling pathway controls larval development, stress resistance and adult lifespan. AGE-1, a homolog of the p110 catalytic subunit of phosphoinositide 3-kinases (PI3K) comprises the major known effector pathway downstream of the insulin receptor, DAF-2. Phospholipid products of AGE-1/PI3K activate AKT/PKB kinase signaling via PDK-1. AKT/PKB signaling antagonizes nuclear translocation of the DAF-16/FOXO transcription factor. Reduced AGE-1/PI3K signaling permits DAF-16 to direct dauer larval arrest and promote long lifespan in adult animals. In order to study the downstream effectors of AGE-1/PI3K signaling in C. elegans, we conducted a genetic screen for mutations that suppress the constitutive dauer arrest phenotype of age-1(mg109) animals. This report describes mutations recovered in a screen for suppressors of the constitutive dauer arrest (daf-C) phenotype of age-1(mg109). Two mutations corresponded to alleles of daf-16. Two mutations were gain-of-function alleles in the genes, akt-1 and pdk-1, encoding phosphoinositide-dependent serine/threonine kinases. A fifth mutation, mg227, located on chromosome X, did not correspond to any known dauer genes, suggesting that mg227 may represent a new component of the insulin pathway. Genetic epistasis analysis by RNAi showed that reproductive development in age-1(mg109);akt-1(mg247) animals was dependent on the presence of pdk-1. Similarly, reproductive development in age-1(mg109);pdk-1(mg261) animals was dependent on akt-1. However, reproductive development in age-1(mg109); mg227 animals required only akt-1, and pdk-1 activity was dispensable in this background. Interestingly, while mg227 suppressed dauer arrest in age-1(mg109) animals, it enhanced the long lifespan phenotype. In contrast, akt-1(mg247) and pdk-1(mg261) did not affect lifespan or stress resistance, while both daf-16 alleles fully suppressed these phenotypes. A screen for suppressors of PI3K

  17. DAF-12 Regulates a Connected Network of Genes to Ensure Robust Developmental Decisions

    Science.gov (United States)

    Stuckenholz, Carsten; Labhart, Paul; Alexiadis, Vassili; Martin, René; Knölker, Hans-Joachim; Fisher, Alfred L.

    2011-01-01

    The nuclear receptor DAF-12 has roles in normal development, the decision to pursue dauer development in unfavorable conditions, and the modulation of adult aging. Despite the biologic importance of DAF-12, target genes for this receptor are largely unknown. To identify DAF-12 targets, we performed chromatin immunoprecipitation followed by hybridization to whole-genome tiling arrays. We identified 1,175 genomic regions to be bound in vivo by DAF-12, and these regions are enriched in known DAF-12 binding motifs and act as DAF-12 response elements in transfected cells and in transgenic worms. The DAF-12 target genes near these binding sites include an extensive network of interconnected heterochronic and microRNA genes. We also identify the genes encoding components of the miRISC, which is required for the control of target genes by microRNA, as a target of DAF-12 regulation. During reproductive development, many of these target genes are misregulated in daf-12(0) mutants, but this only infrequently results in developmental phenotypes. In contrast, we and others have found that null daf-12 mutations enhance the phenotypes of many miRISC and heterochronic target genes. We also find that environmental fluctuations significantly strengthen the weak heterochronic phenotypes of null daf-12 alleles. During diapause, DAF-12 represses the expression of many heterochronic and miRISC target genes, and prior work has demonstrated that dauer formation can suppress the heterochronic phenotypes of many of these target genes in post-dauer development. Together these data are consistent with daf-12 acting to ensure developmental robustness by committing the animal to adult or dauer developmental programs despite variable internal or external conditions. PMID:21814518

  18. Device Assembly Facility (DAF) Glovebox Radioactive Waste Characterization

    International Nuclear Information System (INIS)

    Dominick, J L

    2001-01-01

    The Device Assembly Facility (DAF) at the Nevada Test Site (NTS) provides programmatic support to the Joint Actinide Shock Physics Experimental Research (JASPER) Facility in the form of target assembly. The target assembly activities are performed in a glovebox at DAF and include Special Nuclear Material (SNM). Currently, only activities with transuranic SNM are anticipated. Preliminary discussions with facility personnel indicate that primarily two distributions of SNM will be used: Weapons Grade Plutonium (WG-Pu), and Pu-238 enhanced WG-Pu. Nominal radionuclide distributions for the two material types are included in attachment 1. Wastes generated inside glove boxes is expected to be Transuranic (TRU) Waste which will eventually be disposed of at the Waste Isolation Pilot Plant (WIPP). Wastes generated in the Radioactive Material Area (RMA), outside of the glove box is presumed to be low level waste (LLW) which is destined for disposal at the NTS. The process knowledge quantification methods identified herein may be applied to waste generated anywhere within or around the DAF and possibly JASPER as long as the fundamental waste stream boundaries are adhered to as outlined below. The method is suitable for quantification of waste which can be directly surveyed with the Blue Alpha meter or swiped. An additional quantification methodology which requires the use of a high resolution gamma spectroscopy unit is also included and relies on the predetermined radionuclide distribution and utilizes scaling to measured nuclides for quantification

  19. Dominant negative mutations of Caenorhabditis elegans daf-7 confer a novel developmental phenotype.

    Science.gov (United States)

    Crook, Matt; Grant, Warwick N

    2013-06-01

    TGF-β signaling pathways are involved in the control of development in every member of the animal kingdom. As such, TGF-β ligands are widely divergent yet retain a set of core conserved features, specifically, a pre-protein cleavage site and several conserved ligand domain residues, the disruption of which produces a dominant negative phenotype. We have extended these observations into an invertebrate system by creating a series of loss-of-function Caenorhabditis elegans daf-7 transgenes. When we tested these mutant transgenes in a daf-7/+ background, we saw a molting and excretory canal phenotype. Members of both pathways downstream of daf-4 were required for this phenotype. Our results show that the basic mechanisms of TGF-β function are conserved across the animal kingdom. A subset of our daf-7 mutations also produced an unexpected and novel phenotype. Epistasis experiments demonstrated that both daf-3/-5 and sma-4/-9 were downstream of our mutant daf-7 transgenes, which suggests not only a role for DAF-7 in the control of molting and the development of the excretory system but also that daf-7 and dbl-1 signaling may converge downstream of their shared Type II receptor, daf-4. Our approach may unveil new roles in development for other invertebrate TGF-β ligands. Copyright © 2013 Wiley Periodicals, Inc.

  20. A 44 bp intestine-specific hermaphrodite-specific enhancer from the C. elegans vit-2 vitellogenin gene is directly regulated by ELT-2, MAB-3, FKH-9 and DAF-16 and indirectly regulated by the germline, by daf-2/insulin signaling and by the TGF-β/Sma/Mab pathway.

    Science.gov (United States)

    Goszczynski, Barbara; Captan, Vasile V; Danielson, Alicia M; Lancaster, Brett R; McGhee, James D

    2016-05-01

    The Caenorhabditis elegans vitellogenin genes are transcribed in the intestine of adult hermaphrodites but not of males. A 44-bp region from the vit-2 gene promoter is able largely to reconstitute this tissue-, stage- and sex-specific-expression. This "enhancer" contains a binding site for the DM-domain factor MAB-3, the male-specific repressor of vitellogenesis, as well as an activator site that we show is the direct target of the intestinal GATA factor ELT-2. We further show that the enhancer is directly activated by the winged-helix/forkhead-factor FKH-9, (whose gene has been shown by others to be a direct target of DAF-16), by an unknown activator binding to the MAB-3 site, and by the full C. elegans TGF-β/Sma/Mab pathway acting within the intestine. The vit-2 gene has been shown by others to be repressed by the daf-2/daf-16 insulin signaling pathway, which so strongly influences aging and longevity in C. elegans. We show that the activity of the 44 bp vit-2 enhancer is abolished by loss of daf-2 but is restored by simultaneous loss of daf-16. DAF-2 acts from outside of the intestine but DAF-16 acts both from outside of the intestine and from within the intestine where it binds directly to the same non-canonical target site that interacts with FKH-9. Activity of the 44 bp vit-2 enhancer is also inhibited by loss of the germline, in a manner that is only weakly influenced by DAF-16 but that is strongly influenced by KRI-1, a key downstream effector in the pathway by which germline loss increases C. elegans lifespan. The complex behavior of this enhancer presumably allows vitellogenin gene transcription to adjust to demands of body size, germline proliferation and nutritional state but we suggest that the apparent involvement of this enhancer in aging and longevity "pathways" could be incidental. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. LC–MS Proteomics Analysis of the Insulin/IGF-1-Deficient Caenorhabditis elegans daf-2(e1370) Mutant Reveals Extensive Restructuring of Intermediary Metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Depuydt, Geert; Xie, Fang; Petyuk, Vladislav A.; Smolders, Arne; Brewer, Heather M.; Camp, David G.; Smith, Richard D.; Braeckman, Bart P.

    2014-04-04

    The insulin/IGF-1 receptor is a major known determinant of dauer formation, stress resistance, longevity, and metabolism in Caenorhabditis elegans. In the past, whole-genome transcript profiling was used extensively to study differential gene expression in response to reduced insulin/IGF-1 signaling, including the expression levels of metabolism-associated genes. Taking advantage of the recent developments in quantitative liquid chromatography mass spectrometry (LC–MS)-based proteomics, we profiled the proteomic changes that occur in response to activation of the DAF-16 transcription factor in the germline-less glp-4(bn2);daf-2(e1370) receptor mutant. Strikingly, the daf-2 profile suggests extensive reorganization of intermediary metabolism, characterized by the upregulation of many core intermediary metabolic pathways. These include glycolysis/gluconeogenesis, glycogenesis, pentose phosphate cycle, citric acid cycle, glyoxylate shunt, fatty acid β-oxidation, one-carbon metabolism, propionate and tyrosine catabolism, and complexes I, II, III, and V of the electron transport chain. Interestingly, we found simultaneous activation of reciprocally regulated metabolic pathways, which is indicative of spatiotemporal coordination of energy metabolism and/or extensive post-translational regulation of these enzymes. Finally, this restructuring of daf-2 metabolism is reminiscent to that of hypometabolic dauers, allowing the efficient and economical utilization of internal nutrient reserves and possibly also shunting metabolites through alternative energy-generating pathways to sustain longevity.

  2. LC-MS Proteomics Analysis of the Insulin/IGF-1 Deficient Caenorhabditis elegans daf-2(e1370) Mutant Reveals Extensive Restructuring of Intermediary Metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Depuydt, Geert G.; Xie, Fang; Petyuk, Vladislav A.; Smolders, Arne; Brewer, Heather M.; Camp, David G.; Smith, Richard D.; Braeckman, Bart P.

    2014-02-20

    The insulin/IGF-1 receptor is a major known determinant of dauer formation, stress resistance, longevity and metabolism in C. elegans. In the past, whole-genome transcript profiling was used extensively to study differential gene expression in response to reduced insulin/IGF-1 signaling, including expression levels of metabolism-associated genes. Taking advantage of the recent developments in quantitative liquid chromatography mass-spectrometry (LC-MS) based proteomics, we profiled the proteomic changes that occur in response to activation of the DAF-16 transcription factor in the germline-less glp-4(bn2); daf-2(e1370) receptor mutant. Strikingly, the daf-2 profile suggests extensive reorganization of intermediary metabolism, characterized by the up-regulation of many core intermediary metabolic pathways. These include, glycolysis/gluconeogenesis, glycogenesis, pentose phosphate cycle, citric acid cycle, glyoxylate shunt, fatty acid β-oxidation, one-carbon metabolism, propionate and tyrosine catabolism, and complex I, II, III and V of the electron transport chain. Interestingly, we found simultaneous activation of reciprocally regulated metabolic pathways, which is indicative for spatio-temporal coordination of energy metabolism and/or extensive post-translational regulation of these enzymes. This restructuring of daf-2 metabolism is reminiscent to that of hypometabolic dauers, allowing the efficient and economical utilization of internal nutrient reserves, possibly also shunting metabolites through alternative energy-generating pathways, in order to sustain longevity.

  3. LC–MS Proteomics Analysis of the Insulin/IGF-1-Deficient Caenorhabditis elegans daf-2(e1370) Mutant Reveals Extensive Restructuring of Intermediary Metabolism

    Science.gov (United States)

    2015-01-01

    The insulin/IGF-1 receptor is a major known determinant of dauer formation, stress resistance, longevity, and metabolism in Caenorhabditis elegans. In the past, whole-genome transcript profiling was used extensively to study differential gene expression in response to reduced insulin/IGF-1 signaling, including the expression levels of metabolism-associated genes. Taking advantage of the recent developments in quantitative liquid chromatography mass spectrometry (LC–MS)-based proteomics, we profiled the proteomic changes that occur in response to activation of the DAF-16 transcription factor in the germline-less glp-4(bn2);daf-2(e1370) receptor mutant. Strikingly, the daf-2 profile suggests extensive reorganization of intermediary metabolism, characterized by the upregulation of many core intermediary metabolic pathways. These include glycolysis/gluconeogenesis, glycogenesis, pentose phosphate cycle, citric acid cycle, glyoxylate shunt, fatty acid β-oxidation, one-carbon metabolism, propionate and tyrosine catabolism, and complexes I, II, III, and V of the electron transport chain. Interestingly, we found simultaneous activation of reciprocally regulated metabolic pathways, which is indicative of spatiotemporal coordination of energy metabolism and/or extensive post-translational regulation of these enzymes. This restructuring of daf-2 metabolism is reminiscent to that of hypometabolic dauers, allowing the efficient and economical utilization of internal nutrient reserves and possibly also shunting metabolites through alternative energy-generating pathways to sustain longevity. PMID:24555535

  4. DAFS Storage for High Performance Computing Using MPI-I/O: Design and Experience

    National Research Council Canada - National Science Library

    Velusamy, Vijay

    2004-01-01

    .... DAFS is a well-defined highperformance protocol for file access across a network as well as set of APIs, uDAFS, for user level OS-bypassing application programming, designed to take advantage of RDMA-based transports, such as Virtual Interface Architecture (VIA), InfiniBand Architecture1, and iWARP.

  5. Decay accelerating factor of complement is anchored to cells by a C-terminal glycolipid

    International Nuclear Information System (INIS)

    Medof, M.E.; Walter, E.I.; Roberts, W.L.; Haas, R.; Rosenberry, T.L.

    1986-01-01

    Membrane-associated decay accelerating factor (DAF) of human erythrocytes (E/sup hu/) was analyzed for a C-terminal glycolipid anchoring structure. Automated amino acid analysis of DAF following reductive radiomethylation revealed ethanolamine and glucosamine residues in proportions identical with those present in the E/sup hu/ acetylcholinesterase (AChE) anchor. Cleavage of radiomethylated 70-kilodalton (kDa) DAF with papain released the labeled ethanolamine and glucosamine and generated 61- and 55-kDa DAF products that retained all labeled Lys and labeled N-terminal Asp. Incubation of intact E/sup hu/ with phosphatidylinositol-specific phospholipase C (PI-PLC), which cleaves the anchors in trypanosome membrane form variant surface glycoproteins (mfVSGs) and murine thymocyte Thy-1 antigen, released 15% of the cell-associated DAF antigen. The released 67-kDa PI-PLC DAF derivative retained its ability to decay the classical C3 convertase C4b2a but was unable to membrane-incorporate and displayed physicochemical properties similar to urine DAF, a hydrophilic DAF form that can be isolated for urine. Nitrous acid deamination cleavage of E/sup hu/ DAF at glucosamine following labeling with the lipophilic photoreagent 3-(trifluoromethyl)-3-(m-[ 125 I]iodophenyl)diazirine ([ 125 I]TID) released the [ 125 I]TID label in a parallel fashion as from [ 125 I]TID-labeled AChE. Biosynthetic labeling of HeLa cells with [ 3 H] ethanolamine resulted in rapid 3 H incorporation into both 48-kDa pro-DAF and 72-kDa mature epithelial cell DAF. The findings indicate that DAF and AChE are anchored in E/sup hu/ by the same or a similar glycolipid structure and that, like VSGs, this structure is incorporated into DAF early in DAF biosynthesis prior to processing of pro-DAF in the Golgi

  6. Angiostrongylus cantonensis daf-2 regulates dauer, longevity and stress in Caenorhabditis elegans.

    Science.gov (United States)

    Yan, Baolong; Sun, Weiwei; Shi, Xiaomeng; Huang, Liyang; Chen, Lingzi; Wang, Suhua; Yan, Lanzhu; Liang, Shaohui; Huang, Huicong

    2017-06-15

    The insulin-like signaling (IIS) pathway is considered to be significant in regulating fat metabolism, dauer formation, stress response and longevity in Caenorhabditis elegans. "Dauer hypothesis" indicates that similar IIS transduction mechanism regulates dauer development in free-living nematode C. elegans and the development of infective third-stage larvae (iL3) in parasitic nematodes, and this is bolstered by a few researches on structures and functions of the homologous genes in the IIS pathway cloned from several parasitic nematodes. In this study, we identified the insulin-like receptor encoding gene, Acan-daf-2, from the parasitic nematode Angiostrongylus cantonensis, and determined the genomic structures, transcripts and functions far more thorough in longevity, stress resistance and dauer formation. The sequence of Acan-DAF-2, consisting of 1413 amino acids, contained all of the characteristic domains of insulin-like receptors from other taxa. The expression patterns of Acan-daf-2 in the C. elegans surrogate system showed that pAcan-daf-2:gfp was only expressed in intestine, compared with the orthologue in C. elegans, Ce-daf-2 in both intestine and neurons. In addition to the similar genomic organization to Ce-daf-2, Acan-DAF-2 could also negatively regulate Ce-DAF-16A through nuclear/cytosolic translocation and partially restore the C. elegans daf-2(e1370) mutation in longevity, dauer formation and stress resistance. These findings provided further evidence of the functional conservation of DAF-2 between parasitic nematodes and the free-living nematode C. elegans, and might be significant in understanding the developmental biology of nematode parasites, particularly in the infective process and the host-specificity. Copyright © 2017. Published by Elsevier B.V.

  7. Up-regulation of intestinal vascular endothelial growth factor by Afa/Dr diffusely adhering Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Gaëlle Cane

    Full Text Available BACKGROUND: Angiogenesis has been recently described as a novel component of inflammatory bowel disease pathogenesis. The level of vascular endothelial growth factor (VEGF has been found increased in Crohn's disease and ulcerative colitis mucosa. To question whether a pro-inflammatory Escherichia coli could regulate the expression of VEGF in human intestinal epithelial cells, we examine the response of cultured human colonic T84 cells to infection by E. coli strain C1845 that belongs to the typical Afa/Dr diffusely adhering E. coli family (Afa/Dr DAEC. METHODOLOGY: VEGF mRNA expression was examined by Northern blotting and q-PCR. VEGF protein levels were assayed by ELISA and its bioactivity was analysed in endothelial cells. The bacterial factor involved in VEGF induction was identified using recombinant E. coli expressing Dr adhesin, purified Dr adhesin and lipopolysaccharide. The signaling pathway activated for the up-regulation of VEGF was identified using a blocking monoclonal anti-DAF antibody, Western blot analysis and specific pharmacological inhibitors. PRINCIPAL FINDINGS: C1845 bacteria induce the production of VEGF protein which is bioactive. VEGF is induced by adhering C1845 in both a time- and bacteria concentration-dependent manner. This phenomenon is not cell line dependent since we reproduced this observation in intestinal LS174, Caco2/TC7 and INT407 cells. Up-regulation of VEGF production requires: (1 the interaction of the bacterial F1845 adhesin with the brush border-associated decay accelerating factor (DAF, CD55 acting as a bacterial receptor, and (2 the activation of a Src protein kinase upstream of the activation of the Erk and Akt signaling pathways. CONCLUSIONS: Results demonstrate that a Afa/Dr DAEC strain induces an adhesin-dependent activation of DAF signaling that leads to the up-regulation of bioactive VEGF in cultured human intestinal cells. Thus, these results suggest a link between an entero-adherent, pro

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

    Science.gov (United States)

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

    2013-04-01

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

  9. Localization of a guanylyl cyclase to chemosensory cilia requires the novel ciliary MYND domain protein DAF-25.

    Directory of Open Access Journals (Sweden)

    Victor L Jensen

    2010-11-01

    Full Text Available In harsh conditions, Caenorhabditis elegans arrests development to enter a non-aging, resistant diapause state called the dauer larva. Olfactory sensation modulates the TGF-β and insulin signaling pathways to control this developmental decision. Four mutant alleles of daf-25 (abnormal DAuer Formation were isolated from screens for mutants exhibiting constitutive dauer formation and found to be defective in olfaction. The daf-25 dauer phenotype is suppressed by daf-10/IFT122 mutations (which disrupt ciliogenesis, but not by daf-6/PTCHD3 mutations (which prevent environmental exposure of sensory cilia, implying that DAF-25 functions in the cilia themselves. daf-25 encodes the C. elegans ortholog of mammalian Ankmy2, a MYND domain protein of unknown function. Disruption of DAF-25, which localizes to sensory cilia, produces no apparent cilia structure anomalies, as determined by light and electron microscopy. Hinting at its potential function, the dauer phenotype, epistatic order, and expression profile of daf-25 are similar to daf-11, which encodes a cilium-localized guanylyl cyclase. Indeed, we demonstrate that DAF-25 is required for proper DAF-11 ciliary localization. Furthermore, the functional interaction is evolutionarily conserved, as mouse Ankmy2 interacts with guanylyl cyclase GC1 from ciliary photoreceptors. The interaction may be specific because daf-25 mutants have normally-localized OSM-9/TRPV4, TAX-4/CNGA1, CHE-2/IFT80, CHE-11/IFT140, CHE-13/IFT57, BBS-8, OSM-5/IFT88, and XBX-1/D2LIC in the cilia. Intraflagellar transport (IFT (required to build cilia is not defective in daf-25 mutants, although the ciliary localization of DAF-25 itself is influenced in che-11 mutants, which are defective in retrograde IFT. In summary, we have discovered a novel ciliary protein that plays an important role in cGMP signaling by localizing a guanylyl cyclase to the sensory organelle.

  10. DAFS measurements using the image-plate Weissenberg method

    International Nuclear Information System (INIS)

    Sugioka, N.; Matsumoto, K.; Sasaki, S.; Tanaka, M.; Mori, T.

    1998-01-01

    An instrumental technique for DAFS measurements which can provide site-specific information is proposed. The approach uses (i) focusing optics with parabolic mirrors and a double-crystal monochromator, (ii) the Laue and Bragg settings and (iii) data collection by the image-plate Weissenberg method. Six image exposures are recorded per plate at five intrinsic energies and one reference energy. The single-crystal measurements were performed at the Co K-absorption edge, and the 200, 220 and 311 reflections of CoO and 511 and 911 reflections of Co 3 O 4 were used for analysis. The regression analysis of χ(k), Fourier transforms of k 3 χ(k) and back-Fourier filtering have been performed

  11. Dianxianning improved amyloid β-induced pathological characteristics partially through DAF-2/DAF-16 insulin like pathway in transgenic C. elegans.

    Science.gov (United States)

    Zhi, Dejuan; Wang, Dong; Yang, Wenqi; Duan, Ziyun; Zhu, Shuqian; Dong, Juan; Wang, Na; Wang, Ningbo; Fei, Dongqing; Zhang, Zhanxin; Wang, Xin; Wang, Meizhu; Li, Hongyu

    2017-09-12

    Dianxianning (DXN) is a traditional Chinese formula, and has been approved in China for treating epilepsy since 1996. Here anti-Alzheimer's disease activity of DXN has been reported. DXN improved AD-like symptoms of paralysis and 5-HT sensitivity of transgenic Aβ 1-42 C. elegans. In worms, DXN significantly increased Aβ monomers and decreased the toxic Aβ oligomers, thus reducing Aβ toxicity. DXN significantly suppressed the expression of hsp-16.2 induced by juglone, and up-regulated sod-3 expression. These results indicated that DXN increased stress resistance and protected C. elegans against oxidative stress. Furthermore, DXN could significantly promote DAF-16 nuclear translocation, but it did not activate SKN-1. The inhibitory effect of DXN on the Aβ toxicity was significantly reverted by daf-16 RNAi, rather than skn-1 RNAi or hsf-1 RNAi. These results indicated that DAF-16 is at least partially required for the anti-AD effect of DXN. In conclusion, DXN improved Aβ-induced pathological characteristics partially through DAF-2/DAF-16 insulin like pathway in transgenic worms. Together with our data obtained by Morris water maze test, the results showed that DXN markedly ameliorated cognitive performance impairment induced by scopolamine in mice. All the results support that DXN is a potential drug candidate to treat Alzheimer's diseases.

  12. daf-16/FoxO promotes gluconeogenesis and trehalose synthesis during starvation to support survival.

    Science.gov (United States)

    Hibshman, Jonathan D; Doan, Alexander E; Moore, Brad T; Kaplan, Rebecca Ew; Hung, Anthony; Webster, Amy K; Bhatt, Dhaval P; Chitrakar, Rojin; Hirschey, Matthew D; Baugh, L Ryan

    2017-10-24

    daf-16 /FoxO is required to survive starvation in Caenorhabditis elegans , but how daf-16I FoxO promotes starvation resistance is unclear. We show that daf-16 /FoxO restructures carbohydrate metabolism by driving carbon flux through the glyoxylate shunt and gluconeogenesis and into synthesis of trehalose, a disaccharide of glucose. Trehalose is a well-known stress protectant, capable of preserving membrane organization and protein structure during abiotic stress. Metabolomic, genetic, and pharmacological analyses confirm increased trehalose synthesis and further show that trehalose not only supports survival as a stress protectant but also serves as a glycolytic input. Furthermore, we provide evidence that metabolic cycling between trehalose and glucose is necessary for this dual function of trehalose. This work demonstrates that daf-16 /FoxO promotes starvation resistance by shifting carbon metabolism to drive trehalose synthesis, which in turn supports survival by providing an energy source and acting as a stress protectant.

  13. daf-16/FoxO promotes gluconeogenesis and trehalose synthesis during starvation to support survival

    Science.gov (United States)

    Hibshman, Jonathan D; Doan, Alexander E; Moore, Brad T; Kaplan, Rebecca EW; Hung, Anthony; Webster, Amy K; Bhatt, Dhaval P; Chitrakar, Rojin; Hirschey, Matthew D

    2017-01-01

    daf-16/FoxO is required to survive starvation in Caenorhabditis elegans, but how daf-16IFoxO promotes starvation resistance is unclear. We show that daf-16/FoxO restructures carbohydrate metabolism by driving carbon flux through the glyoxylate shunt and gluconeogenesis and into synthesis of trehalose, a disaccharide of glucose. Trehalose is a well-known stress protectant, capable of preserving membrane organization and protein structure during abiotic stress. Metabolomic, genetic, and pharmacological analyses confirm increased trehalose synthesis and further show that trehalose not only supports survival as a stress protectant but also serves as a glycolytic input. Furthermore, we provide evidence that metabolic cycling between trehalose and glucose is necessary for this dual function of trehalose. This work demonstrates that daf-16/FoxO promotes starvation resistance by shifting carbon metabolism to drive trehalose synthesis, which in turn supports survival by providing an energy source and acting as a stress protectant. PMID:29063832

  14. ins-7 Gene expression is partially regulated by the DAF-16/IIS signaling pathway in Caenorhabditis elegans under celecoxib intervention.

    Directory of Open Access Journals (Sweden)

    Shanqing Zheng

    Full Text Available DAF-16 target genes are employed as reporters of the insulin/IGF-1 like signal pathway (IIS, and this is notably true when Caenorhabditis elegans (C. elegans is used to study the action of anti-aging compounds on IIS activity. However, some of these genes may not be specific to DAF-16, even if their expression levels are altered when DAF-16 is activated. Celecoxib was reported to extend the lifespan of C. elegans through activation of DAF-16. Our results confirmed the function of celecoxib on aging; however, we found that the expression of ins-7, a DAF-16 target gene, was abnormally regulated by celecoxib. ins-7 plays an important role in regulating aging, and its expression is suppressed in C. elegans when DAF-16 is activated. However, we found that celecoxib upregulated the expression of ins-7 in contrast to its role in DAF-16 activation. Our subsequent analysis indicated that the expression level of ins-7 in C. elegans was negatively regulated by DAF-16 activity. Additionally, its expression was also positively regulated by DAF-16-independent mechanisms, at least following external pharmacological intervention. Our study suggests that ins-7 is not a specific target gene of DAF-16, and should not be chosen as a reporter for IIS activity. This conclusion is important in the study of INSs on aging in C. elegans, especially under the circumstance of drug intervention.

  15. ins-7 Gene expression is partially regulated by the DAF-16/IIS signaling pathway in Caenorhabditis elegans under celecoxib intervention.

    Science.gov (United States)

    Zheng, Shanqing; Liao, Sentai; Zou, Yuxiao; Qu, Zhi; Liu, Fan

    2014-01-01

    DAF-16 target genes are employed as reporters of the insulin/IGF-1 like signal pathway (IIS), and this is notably true when Caenorhabditis elegans (C. elegans) is used to study the action of anti-aging compounds on IIS activity. However, some of these genes may not be specific to DAF-16, even if their expression levels are altered when DAF-16 is activated. Celecoxib was reported to extend the lifespan of C. elegans through activation of DAF-16. Our results confirmed the function of celecoxib on aging; however, we found that the expression of ins-7, a DAF-16 target gene, was abnormally regulated by celecoxib. ins-7 plays an important role in regulating aging, and its expression is suppressed in C. elegans when DAF-16 is activated. However, we found that celecoxib upregulated the expression of ins-7 in contrast to its role in DAF-16 activation. Our subsequent analysis indicated that the expression level of ins-7 in C. elegans was negatively regulated by DAF-16 activity. Additionally, its expression was also positively regulated by DAF-16-independent mechanisms, at least following external pharmacological intervention. Our study suggests that ins-7 is not a specific target gene of DAF-16, and should not be chosen as a reporter for IIS activity. This conclusion is important in the study of INSs on aging in C. elegans, especially under the circumstance of drug intervention.

  16. Linking the environment, DAF-7/TGFβ signaling and LAG-2/DSL ligand expression in the germline stem cell niche.

    Science.gov (United States)

    Pekar, Olga; Ow, Maria C; Hui, Kailyn Y; Noyes, Marcus B; Hall, Sarah E; Hubbard, E Jane Albert

    2017-08-15

    The developmental accumulation of proliferative germ cells in the C. elegans hermaphrodite is sensitive to the organismal environment. Previously, we found that the TGFβ signaling pathway links the environment and proliferative germ cell accumulation. Neuronal DAF-7/TGFβ causes a DAF-1/TGFβR signaling cascade in the gonadal distal tip cell (DTC), the germline stem cell niche, where it negatively regulates a DAF-3 SMAD and DAF-5 Sno-Ski. LAG-2, a founding DSL ligand family member, is produced in the DTC and activates the GLP-1/Notch receptor on adjacent germ cells to maintain germline stem cell fate. Here, we show that DAF-7/TGFβ signaling promotes expression of lag-2 in the DTC in a daf-3- dependent manner. Using ChIP and one-hybrid assays, we find evidence for direct interaction between DAF-3 and the lag-2 promoter. We further identify a 25 bp DAF-3 binding element required for the DTC lag-2 reporter response to the environment and to DAF-7/TGFβ signaling. Our results implicate DAF-3 repressor complex activity as a key molecular mechanism whereby the environment influences DSL ligand expression in the niche to modulate developmental expansion of the germline stem cell pool. © 2017. Published by The Company of Biologists Ltd.

  17. Two potential hookworm DAF-16 target genes, SNR-3 and LPP-1: gene structure, expression profile, and implications of a cis-regulatory element in the regulation of gene expression.

    Science.gov (United States)

    Gao, Xin; Goggin, Kevin; Dowling, Camille; Qian, Jason; Hawdon, John M

    2015-01-08

    Hookworms infect nearly 700 million people, causing anemia and developmental stunting in heavy infections. Little is known about the genomic structure or gene regulation in hookworms, although recent publication of draft genome assemblies has allowed the first investigations of these topics to be undertaken. The transcription factor DAF-16 mediates multiple developmental pathways in the free living nematode Caenorhabditis elegans, and is involved in the recovery from the developmentally arrested L3 in hookworms. Identification of downstream targets of DAF-16 will provide a better understanding of the molecular mechanism of hookworm infection. Genomic Fragment 2.23 containing a DAF-16 binding element (DBE) was used to identify overlapping complementary expressed sequence tags (ESTs). These sequences were used to search a draft assembly of the Ancylostoma caninum genome, and identified two neighboring genes, snr-3 and lpp-1, in a tail-to-tail orientation. Expression patterns of both genes during parasitic development were determined by qRT-PCR. DAF-16 dependent cis-regulatory activity of fragment 2.23 was investigated using an in vitro reporter system. The snr-3 gene spans approximately 5.6 kb in the genome and contains 3 exons and 2 introns, and contains the DBE in its 3' untranslated region. Downstream from snr-3 in a tail-to-tail arrangement is the gene lpp-1. The lpp-1 gene spans more than 6 kb and contains 10 exons and 9 introns. The A. caninum genome contains 2 apparent splice variants, but there are 7 splice variants in the A. ceylanicum genome. While the gene order is similar, the gene structures of the hookworm genes differ from their C. elegans orthologs. Both genes show peak expression in the late L4 stage. Using a cell culture based expression system, fragment 2.23 was found to have both DAF-16-dependent promoter and enhancer activity that required an intact DBE. Two putative DAF-16 targets were identified by genome wide screening for DAF-16 binding

  18. Monascin from Monascus-Fermented Products Reduces Oxidative Stress and Amyloid-β Toxicity via DAF-16/FOXO in Caenorhabditis elegans.

    Science.gov (United States)

    Shi, Yeu-Ching; Pan, Tzu-Ming; Liao, Vivian Hsiu-Chuan

    2016-09-28

    Amyloid-β (Aβ)-induced oxidative stress and toxicity are leading risk factors for Alzheimer's disease (AD). Monascin (MS) is a novel compound proposed for antioxidative stress applications and is derived from an edible fungus secondary metabolite. This study assessed the effects of MS on oxidative stress, paralysis, Aβ accumulation, and lifespan in the nematode Caenorhabditis elegans and investigated its underlying mechanisms of action. The results showed that MS increased the survival of C. elegans under juglone-induced oxidative stress and attenuated endogenous levels of reactive oxygen species. Furthermore, MS induced a decline in Aβ-induced paralysis phenotype and Aβ deposits in the transgenic strains CL4176 and CL2006 of C. elegans, which expresses human muscle-specific Aβ1-42 in the cytoplasm of body wall muscle cells. In addition, mRNA levels of strain CL4176 of several antioxidant genes (sod-1, sod-2, sod-3, hsp16.2) and daf-16 were up-regulated by MS treatment when compared to the nontreated controls. Further evidence showed that MS treatment in C. elegans strains lacking DAF-16/FOXO did not affect paralysis or lifespan phenotypes. The findings indicate that MS reduces oxidative stress and Aβ toxicity via DAF-16 in C. elegans, suggesting that MS can be used for the prevention of AD-associated oxidative stress complications.

  19. DAF-16 and TCER-1 Facilitate Adaptation to Germline Loss by Restoring Lipid Homeostasis and Repressing Reproductive Physiology in C. elegans

    Science.gov (United States)

    Amrit, Francis Raj Gandhi; Steenkiste, Elizabeth Marie; Ratnappan, Ramesh; Chen, Shaw-Wen; McClendon, T. Brooke; Kostka, Dennis; Yanowitz, Judith; Olsen, Carissa Perez; Ghazi, Arjumand

    2016-01-01

    Elimination of the proliferating germline extends lifespan in C. elegans. This phenomenon provides a unique platform to understand how complex metazoans retain metabolic homeostasis when challenged with major physiological perturbations. Here, we demonstrate that two conserved transcription regulators essential for the longevity of germline-less adults, DAF-16/FOXO3A and TCER-1/TCERG1, concurrently enhance the expression of multiple genes involved in lipid synthesis and breakdown, and that both gene classes promote longevity. Lipidomic analyses revealed that key lipogenic processes, including de novo fatty acid synthesis, triglyceride production, desaturation and elongation, are augmented upon germline removal. Our data suggest that lipid anabolic and catabolic pathways are coordinately augmented in response to germline loss, and this metabolic shift helps preserve lipid homeostasis. DAF-16 and TCER-1 also perform essential inhibitory functions in germline-ablated animals. TCER-1 inhibits the somatic gene-expression program that facilitates reproduction and represses anti-longevity genes, whereas DAF-16 impedes ribosome biogenesis. Additionally, we discovered that TCER-1 is critical for optimal fertility in normal adults, suggesting that the protein acts as a switch supporting reproductive fitness or longevity depending on the presence or absence of the germline. Collectively, our data offer insights into how organisms adapt to changes in reproductive status, by utilizing the activating and repressive functions of transcription factors and coordinating fat production and degradation. PMID:26862916

  20. Criticality Safety Evaluation for the TACS at DAF

    Energy Technology Data Exchange (ETDEWEB)

    Percher, C. M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Heinrichs, D. P. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2011-06-10

    Hands-on experimental training in the physical behavior of multiplying systems is one of ten key areas of training required for practitioners to become qualified in the discipline of criticality safety as identified in DOE-STD-1135-99, Guidance for Nuclear Criticality Safety Engineer Training and Qualification. This document is a criticality safety evaluation of the training activities and operations associated with HS-3201-P, Nuclear Criticality 4-Day Training Course (Practical). This course was designed to also address the training needs of nuclear criticality safety professionals under the auspices of the NNSA Nuclear Criticality Safety Program1. The hands-on, or laboratory, portion of the course will utilize the Training Assembly for Criticality Safety (TACS) and will be conducted in the Device Assembly Facility (DAF) at the Nevada Nuclear Security Site (NNSS). The training activities will be conducted by Lawrence Livermore National Laboratory following the requirements of an Integrated Work Sheet (IWS) and associated Safety Plan. Students will be allowed to handle the fissile material under the supervision of an LLNL Certified Fissile Material Handler.

  1. Structural and functional characterization of a novel gene, Hc-daf-22, from the strongylid nematode Haemonchus contortus.

    Science.gov (United States)

    Guo, Xiaolu; Zhang, Hongli; Zheng, Xiuping; Zhou, Qianjin; Yang, Yi; Chen, Xueqiu; Du, Aifang

    2016-07-29

    The strongylid nematode Haemonchus contortus is a parasite of major concern for modern livestock husbandry because hostile environmental conditions may induce diapause in the early fourth-stage larvae. A new gene Hc-daf-22 was identified which is the homologue of Ce-daf-22 and human SCPx. Genome walking and RACE were performed to obtain the whole cDNA and genomic sequence of this gene. Using qRT-PCR with all developmental stages as templates to explore the transcription level and micro-injection was applied to confirm the promoter activity of the 5'-flanking region. Overexpression, rescue and RNA interference experiments were performed in N2, daf-22 mutant (ok 693) strains of C. elegans to study the gene function of Hc-daf-22. The full length gene of Hc-daf-22 (6,939 bp) contained 16 exons separated by 15 introns, and encoded a cDNA of 1,602 bp (533 amino acids, estimated at about 59.3 kDa) with a peak in L3 and L4 in transcriptional level. The Hc-DAF-22 protein was consisted of a 3-oxoacyl-CoA thiolase domain and a SCP2 domain and evolutionarily conserved. The 1,548 bp fragment upstream of the 5'-flanking region was confirmed to have promoter activity compared with 5'-flanking region of Ce-daf-22. The rescue experiment by micro-injection of daf-22 (ok693) mutant strain showed significant increase in body size and brood size in the rescued worms with significantly reduced or completely absent fat granules confirmed by Oil red O staining, indicating that Hc-daf-22 could partially rescue the function of Ce-daf-22. Furthermore, RNAi with Hc-daf-22 could partially silence the endogenous Ce-daf-22 in N2 worms and mimic the phenotype of daf-22 (ok693) mutants. The gene Hc-daf-22 was isolated and its function identified using C. elegans as a model organism. Our results indicate that Hc-daf-22 shared similar characteristics and function with Ce-daf-22 and may play an important role in peroxisomal β-oxidation and the development in H. contortus.

  2. The solution structure of the forkhead box-O DNA binding domain of Brugia malayi DAF-16a.

    Science.gov (United States)

    Casper, Sarah K; Schoeller, Scott J; Zgoba, Danielle M; Phillips, Andrew J; Morien, Thomas J; Chaffee, Gary R; Sackett, Peter C; Peterson, Francis C; Crossgrove, Kirsten; Veldkamp, Christopher T

    2014-12-01

    Brugia malayi is a parasitic nematode that causes lymphatic filariasis in humans. Here the solution structure of the forkhead DNA binding domain of Brugia malayi DAF-16a, a putative ortholog of Caenorhabditis elegans DAF-16, is reported. It is believed to be the first structure of a forkhead or winged helix domain from an invertebrate. C. elegans DAF-16 is involved in the insulin/IGF-I signaling pathway and helps control metabolism, longevity, and development. Conservation of sequence and structure with human FOXO proteins suggests that B. malayi DAF-16a is a member of the FOXO family of forkhead proteins. © 2014 Wiley Periodicals, Inc.

  3. Morphogenesis of Strongyloides stercoralis infective larvae requires the DAF-16 ortholog FKTF-1.

    Directory of Open Access Journals (Sweden)

    Michelle L Castelletto

    2009-04-01

    Full Text Available Based on metabolic and morphological similarities between infective third-stage larvae of parasitic nematodes and dauer larvae of Caenorhabditis elegans, it is hypothesized that similar genetic mechanisms control the development of these forms. In the parasite Strongyloides stercoralis, FKTF-1 is an ortholog of DAF-16, a forkhead transcription factor that regulates dauer larval development in C. elegans. Using transgenesis, we investigated the role of FKTF-1 in S. stercoralis' infective larval development. In first-stage larvae, GFP-tagged recombinant FKTF-1b localizes to the pharynx and hypodermis, tissues remodeled in infective larvae. Activating and inactivating mutations at predicted AKT phosphorylation sites on FKTF-1b give constitutive cytoplasmic and nuclear localization of the protein, respectively, indicating that its post-translational regulation is similar to other FOXO-class transcription factors. Mutant constructs designed to interfere with endogenous FKTF-1b function altered the intestinal and pharyngeal development of the larvae and resulted in some transgenic larvae failing to arrest in the infective stage. Our findings indicate that FKTF-1b is required for proper morphogenesis of S. stercoralis infective larvae and support the overall hypothesis of similar regulation of dauer development in C. elegans and the formation of infective larvae in parasitic nematodes.

  4. Cholesterol regulates DAF-16 nuclear localization and fasting-induced longevity in C. elegans.

    Science.gov (United States)

    Ihara, Akiko; Uno, Masaharu; Miyatake, Koichi; Honjoh, Sakiko; Nishida, Eisuke

    2017-01-01

    Cholesterol has attracted significant attention as a possible lifespan regulator. It has been reported that serum cholesterol levels have an impact on mortality due to age-related disorders such as cardiovascular disease. Diet is also known to be an important lifespan regulator. Dietary restriction retards the onset of age-related diseases and extends lifespan in various organisms. Although cholesterol and dietary restriction are known to be lifespan regulators, it remains to be established whether cholesterol is involved in dietary restriction-induced longevity. Here, we show that cholesterol deprivation suppresses longevity induced by intermittent fasting, which is one of the dietary restriction regimens that effectively extend lifespan. We also found that cholesterol is required for the fasting-induced upregulation of transcriptional target genes such as the insulin/IGF-1 pathway effector DAF-16 and that cholesterol deprivation suppresses the long lifespan of the insulin/IGF-1 receptor daf-2 mutant. Remarkably, we found that cholesterol plays an important role in the fasting-induced nuclear accumulation of DAF-16. Moreover, knockdown of the cholesterol-binding protein NSBP-1, which has been shown to bind to DAF-16 in a cholesterol-dependent manner and to regulate DAF-16 activity, suppresses both fasting-induced longevity and DAF-16 nuclear accumulation. Furthermore, this suppression was not additive to the cholesterol deprivation-induced suppression, which suggests that NSBP-1 mediates, at least in part, the action of cholesterol to promote fasting-induced longevity and DAF-16 nuclear accumulation. These findings identify a novel role for cholesterol in the regulation of lifespan. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. A Tandem Repeat in Decay Accelerating Factor 1 Is Associated with Severity of Murine Mercury-Induced Autoimmunity

    Directory of Open Access Journals (Sweden)

    David M. Cauvi

    2014-01-01

    Full Text Available Decay accelerating factor (DAF, a complement-regulatory protein, protects cells from bystander complement-mediated lysis and negatively regulates T cells. Reduced expression of DAF occurs in several systemic autoimmune diseases including systemic lupus erythematosus, and DAF deficiency exacerbates disease in several autoimmune models, including murine mercury-induced autoimmunity (mHgIA. Daf1, located within Hmr1, a chromosome 1 locus associated in DBA/2 mice with resistance to mHgIA, could be a candidate. Here we show that reduced Daf1 transcription in lupus-prone mice was not associated with a reduction in the Daf1 transcription factor SP1. Studies of NZB mice congenic for the mHgIA-resistant DBA/2 Hmr1 locus suggested that Daf1 expression was controlled by the host genome and not the Hmr1 locus. A unique pentanucleotide repeat variant in the second intron of Daf1 in DBA/2 mice was identified and shown in F2 intercrosses to be associated with less severe disease; however, analysis of Hmr1 congenics indicated that this most likely reflected the presence of autoimmunity-predisposing genetic variants within the Hmr1 locus or that Daf1 expression is mediated by the tandem repeat in epistasis with other genetic variants present in autoimmune-prone mice. These studies argue that the effect of DAF on autoimmunity is complex and may require multiple genetic elements.

  6. The longevity effect of echinacoside in Caenorhabditis elegans mediated through daf-16.

    Science.gov (United States)

    Wang, Xue; Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun

    2015-01-01

    Echinacoside (ECH), a natural polyphenolic compound, has been reported to possess important pharmacological activities. However, very little is known about whether or how ECH affects longevity in vivo. We have examined the effects of ECH on the life span and stress tolerance in Caenorhabditis elegans. Our studies demonstrate that the life span of wild-type worms could be extended in the presence of ECH. Furthermore, ECH was found to increase tolerance of worms to heat shock and oxidative stress, while not exerting any influence on pharyngeal pumping rate and progeny production. Our mechanistic studies indicate that supplementation of ECH increases the transcript level of daf-16. ECH treatment also modulates the nuclear localization and transcriptional activities of daf-16, thus fine tunes the expression of daf-16 target genes to promote longevity and increases stress response in C. elegans. Overall, this work reveals the longevity effect of ECH and elucidates the underpinning mechanisms.

  7. DAF-16-dependent suppression of immunity during reproduction in Caenorhabditis elegans.

    Science.gov (United States)

    Miyata, Sachiko; Begun, Jakob; Troemel, Emily R; Ausubel, Frederick M

    2008-02-01

    To further understand how the nematode Caenorhabditis elegans defends itself against pathogen attack, we analyzed enhanced pathogen resistance (epr) mutants obtained from a forward genetic screen. We also examined several well-characterized sterile mutants that exhibit an Epr phenotype. We found that sterility and pathogen resistance are highly correlated and that resistance in both epr and sterile mutants is dependent on DAF-16 activity. Our data indicate that a DAF-16-dependent signaling pathway distinct from previously described pathways is involved in the activation of genes that confer resistance to bacterial pathogens. The timing of DAF-16-dependent gene activation in sterile mutants coincides with the onset of embryonic development in wild-type animals, suggesting that signals from developing embryos normally downregulate the immune response.

  8. Rifampicin reduces advanced glycation end products and activates DAF-16 to increase lifespan in Caenorhabditis elegans.

    Science.gov (United States)

    Golegaonkar, Sandeep; Tabrez, Syed S; Pandit, Awadhesh; Sethurathinam, Shalini; Jagadeeshaprasad, Mashanipalya G; Bansode, Sneha; Sampathkumar, Srinivasa-Gopalan; Kulkarni, Mahesh J; Mukhopadhyay, Arnab

    2015-06-01

    Advanced glycation end products (AGEs) are formed when glucose reacts nonenzymatically with proteins; these modifications are implicated in aging and pathogenesis of many age-related diseases including type II diabetes, atherosclerosis, and neurodegenerative disorders. Thus, pharmaceutical interventions that can reduce AGEs may delay age-onset diseases and extend lifespan. Using LC-MS(E), we show that rifampicin (RIF) reduces glycation of important cellular proteins in vivo and consequently increases lifespan in Caenorhabditis elegans by up to 60%. RIF analog rifamycin SV (RSV) possesses similar properties, while rifaximin (RMN) lacks antiglycation activity and therefore fails to affect lifespan positively. The efficacy of RIF and RSV as potent antiglycating agents may be attributed to the presence of a p-dihydroxyl moiety that can potentially undergo spontaneous oxidation to yield highly reactive p-quinone structures, a feature absent in RMN. We also show that supplementing rifampicin late in adulthood is sufficient to increase lifespan. For its effect on longevity, rifampicin requires DAF-18 (nematode PTEN) as well as JNK-1 and activates DAF-16, the FOXO homolog. Interestingly, the drug treatment modulates transcription of a different subset of DAF-16 target genes, those not controlled by the conserved Insulin-IGF-1-like signaling pathway. RIF failed to increase the lifespan of daf-16 null mutant despite reducing glycation, showing thereby that DAF-16 may not directly affect AGE formation. Together, our data suggest that the dual ability to reduce glycation in vivo and activate prolongevity processes through DAF-16 makes RIF and RSV effective lifespan-extending interventions. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  9. DESIGN OF A DISSOLVED AIR FLOAT (DAF) IN THE TREATMENT OF WASTE WATER A TEXTILE

    OpenAIRE

    Salas Colotta, G.

    2014-01-01

    We presented the design of a dissolved air flotation system (DAF) to separate coagulated solids (dye) in the wastewater of a textile plant. The obtained yields of removal of suspended solids (SS) they are 82%. The size of the float to treat 35 m3/h of residual water of a textile is 5,7 m. Se presenta el diseño de un flotador por aire disuelto (DAF) para separar sólidos coagulados y floculados (tinte) provenientes de los efluentes de una planta textil. Los rendimientos obtenidos de remoción...

  10. DAF-16 and Δ9 desaturase genes promote cold tolerance in long-lived Caenorhabditis elegans age-1 mutants.

    Directory of Open Access Journals (Sweden)

    Fiona R Savory

    Full Text Available In Caenorhabditis elegans, mutants of the conserved insulin/IGF-1 signalling (IIS pathway are long-lived and stress resistant due to the altered expression of DAF-16 target genes such as those involved in cellular defence and metabolism. The three Δ(9 desaturase genes, fat-5, fat-6 and fat-7, are included amongst these DAF-16 targets, and it is well established that Δ(9 desaturase enzymes play an important role in survival at low temperatures. However, no assessment of cold tolerance has previously been reported for IIS mutants. We demonstrate that long-lived age-1(hx546 mutants are remarkably resilient to low temperature stress relative to wild type worms, and that this is dependent upon daf-16. We also show that cold tolerance following direct transfer to low temperatures is increased in wild type worms during the facultative, daf-16 dependent, dauer stage. Although the cold tolerant phenotype of age-1(hx546 mutants is predominantly due to the Δ(9 desaturase genes, additional transcriptional targets of DAF-16 are also involved. Surprisingly, survival of wild type adults following a rapid temperature decline is not dependent upon functional daf-16, and cellular distributions of a DAF-16::GFP fusion protein indicate that DAF-16 is not activated during low temperature stress. This suggests that cold-induced physiological defences are not specifically regulated by the IIS pathway and DAF-16, but expression of DAF-16 target genes in IIS mutants and dauers is sufficient to promote cross tolerance to low temperatures in addition to other forms of stress.

  11. Intrinsic JNK-MAPK pathway involvement requires daf-16-mediated immune response during Shigella flexneri infection in C. elegans.

    Science.gov (United States)

    Marudhupandiyan, Shanmugam; Balamurugan, Krishnaswamy

    2017-06-01

    The c-Jun N-terminal kinase-mitogen-activated protein kinase (JNK-MAPK) pathway assists in modulating signals for growth, survival, and metabolism, thereby coordinating many cellular events during normal and stress conditions. To understand the role of the JNK-MAPK pathway during bacterial infection, an in vivo model organism Caenorhabditis elegans was used. In order to check the involvement of the JNK-MAPK pathway, the survival rate of C. elegans wild type (WT), and JNK-MAPK pathway mutant worms' upon exposure to selective Gram-positive and Gram-negative pathogenic bacteria, was studied. Among the pathogens, Shigella flexneri M9OT was found to efficiently colonize inside the WT and JNK-MAPK pathway mutant worms. qPCR studies had suggested that the above pathway-specific genes kgb-2 and jnk-1 were prominently responsible for the immune response elicited by the host during the M9OT infection. In addition, daf-16, which is a major transcription factor of the insulin/insulin growth factor-1 signaling (IIS) pathway, was also found to be involved during the host response. Crosstalk between IIS and JNK-MAPK pathways has probably been involved in the activation of the host immune system, which consequently leads to lifespan extension. Furthermore, it is also observed that daf-16 activation by JNK-MAPK pathway leads to antimicrobial response, by activating lys-7 expression. These findings suggest that JNK-MAPK is not the sole pathway that enhances the immunity of the host. Nonetheless, the IIS pathway bridges the JNK-MAPK pathway that influences in protecting the host in counter to the M9OT infection.

  12. Evaluation of Dissolved Air Flotation (DAF for Pretreatment of the Karoon River Water

    Directory of Open Access Journals (Sweden)

    Naeim Banisaeid

    2007-09-01

    Full Text Available The efficiency of a pilot dissolved air flotation (DAF unit is evaluated. It is the objective of the present study to determine the removal efficiency of DAF in removing turbidity and organic matter from theKaroonRiverfeeding a water treatment plant. Water quality investigations over the study period revealed that, thanks to the self-purification process in the river, the Karoon water quality is acceptable with respect to total organic carbon (TOC (never exceeding 2.89 mg/l but its turbidity has great fluctuations (from as low as 42 to 1,000 NTU due to the nature of the river. Its true color is in desirable conditions. Suspended solids removal efficiency of the pilot DAF unit varied from 38% to 95%, with an average level of 72%. The results from this study indicate that DAF removal efficiency is inversely related to the volume of inflow of solids into the system so that increasing TSS decreases removal efficiency. The high turbidity level in the absence of a primary sedimentation unit causes the flotation system to lose its desired efficiency. FAD cannot be, therefore, recommended for water treatment plants fed by the Karoon water unless a pretreatment unit is used. Furthermore, as FAD's TOC removal efficiency varies by up to 82%, and since part of the organic content includes volatile organic matter causing odors and undesirable taste, FAD is recommended as a complementary process in the treatment of high quality water.

  13. The Future of Architecture Collaborative Information Sharing: DoDAF Version 2.03 Updates

    Science.gov (United States)

    2012-04-30

    Salamander x Select Solution Factory Select Business Solutions BPMN , UML x SimonTool Simon Labs x SimProcess CACI BPMN x System Architecture Management...for DoDAF Mega UML x Metastorm ProVision Metastorm BPMN x Naval Simulation System - 4 Aces METRON x NetViz CA x OPNET OPNET x Tool Name Vendor Primary

  14. High Energy X-Ray System Specification for the Device Assembly Facility (DAF) at the NNSS

    International Nuclear Information System (INIS)

    Fry, David A.

    2012-01-01

    This specification establishes requirements for an X-Ray System to be used at the Device Assembly Facility (DAF) at the Nevada National Security Site (NNSS) to support radiography of experimental assemblies for Laboratory (LANL, LLNL, SNL) programs conducting work at the NNSS.

  15. Waste management in the meat processing industry: Conversion of paunch and DAF sludge into solid fuel.

    Science.gov (United States)

    Hamawand, Ihsan; Pittaway, Pam; Lewis, Larry; Chakrabarty, Sayan; Caldwell, Justin; Eberhard, Jochen; Chakraborty, Arpita

    2017-02-01

    This article addresses the novel dewatering process of immersion-frying of paunch and dissolved air flotation (DAF) sludge to produce high energy pellets. Literature have been analysed to address the feasibility of replacing conventional boiler fuel at meat processing facilities with high energy paunch-DAF sludge pellets (capsules). The value proposition of pelleting and frying this mixture into energy pellets is based on a Cost-Benefit Analysis (CBA). The CBA is based on information derived from the literature and consultation with the Australian Meat Processing Industry. The calorific properties of a mixture of paunch cake solids and DAF sludge were predicted from literature and industry consultation to validate the product. This study shows that the concept of pelletizing and frying paunch is economically feasible. The complete frying and dewatering of the paunch and DAF sludge mixture produces pellets with energy content per kilogram equivalent to coal. The estimated cost of this new product is half the price of coal and the payback period is estimated to be between 1.8 and 3.2years. Further research is required for proof of concept, and to identify the technical challenges associated with integrating this technology into existing meat processing plants. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  16. Doxycyclin ameliorates a starvation-induced germline tumor in C. elegans daf-18/PTEN mutant background.

    Science.gov (United States)

    Wolf, Tim; Qi, Wenjing; Schindler, Verena; Runkel, Eva Diana; Baumeister, Ralf

    2014-08-01

    Managing available resources is a key necessity of each organism to cope with the environment. The nematode C. elegans responds to nutritional deprivation or harsh environmental conditions with a multitude of developmental adaptations, among them a starvation-induced quiescence at early larval development (L1). daf-18, the C. elegans homolog of the human tumor suppressor gene PTEN, is essential for the maintenance of survival and germline stem cell arrest during the L1 diapause. We show here that daf-18 mutants, independently to their failure to maintain G2 arrest of the primordial germ cells, develop a gonad phenotype after refeeding. This highly penetrant gonadal phenotype is further enhanced by a mutation in shc-1, encoding a protein homologous to the human adaptor ShcA. Features of this phenotype are a tumor-like phenotype encompassing hyper-proliferation of germ cell nuclei and disruption/invasion of the basement membrane surrounding the gonad. The penetrance of this phenotype is reduced by decreasing starvation temperature. In addition, it is also ameliorated in a dose-dependent way by exposure to the antibiotic doxycyclin either during starvation or during subsequent refeeding. Since, in eukaryotic cells, doxycyclin specifically blocks mitochondrial translation, our results suggest that daf-18 and shc-1;daf-18 mutants fail to adapt mitochondrial activity to reduced nutritional availability during early larval developing. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Increased Protein Stability and Decreased Protein Turnover in the Caenorhabditis elegans Ins/IGF-1 daf-2 Mutant.

    Science.gov (United States)

    Depuydt, Geert; Shanmugam, Nilesh; Rasulova, Madina; Dhondt, Ineke; Braeckman, Bart P

    2016-12-01

    In Caenorhabditis elegans, cellular proteostasis is likely essential for longevity. Autophagy has been shown to be essential for lifespan extension of daf-2 insulin/IGF mutants. Therefore, it can be hypothesized that daf-2 mutants achieve this phenotype by increasing protein turnover. However, such a mechanism would exert a substantial energy cost. By using classical 35 S pulse-chase labeling, we observed that protein synthesis and degradation rates are decreased in young adults of the daf-2 insulin/IGF mutants. Although reduction of protein turnover may be energetically favorable, it may lead to accumulation and aggregation of damaged proteins. As this has been shown not to be the case in daf-2 mutants, another mechanism must exist to maintain proteostasis in this strain. We observed that proteins isolated from daf-2 mutants are more soluble in acidic conditions due to increased levels of trehalose. This suggests that trehalose may decrease the potential for protein aggregation and increases proteostasis in the daf-2 mutants. We postulate that daf-2 mutants save energy by decreasing protein turnover rates and instead stabilize their proteome by trehalose. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America.

  18. Oleanolic acid activates daf-16 to increase lifespan in Caenorhabditis elegans

    International Nuclear Information System (INIS)

    Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun

    2015-01-01

    Oleanolic acid (OA) is an active ingredient in natural plants. It has been reported to possess a variety of pharmacological activities, but very little is known about its effects of anti-aging. We investigate here whether OA has an impact on longevity in vivo, and more specifically, we have examined effects of OA on the lifespan and stress tolerance in Caenorhabditis elegans (C. elegans). Our results showed that OA could extend the lifespan, increase its stress resistance and reduce the intracellular reactive oxygen species (ROS) in wild-type worms. Moreover, we have found that OA-induced longevity may not be associated with the calorie restriction (CR) mechanism. Our mechanistic studies using daf-16 loss-of-function mutant strains (GR1307) indicated that the extension of lifespan by OA requires daf-16. In addition, OA treatment could also modulate the nuclear localization, and the quantitative real-time PCR results revealed that up-regulation of daf-16 target genes such as sod-3, hsp-16.2 and ctl-1 could prolong lifespan and increase stress response in C. elegans. This study overall uncovers the longevity effect of OA and its underpinning mechanisms. - Graphical abstract: Oleanolic acid modulates the activity of DAF-16 to promote longevity and increase stress resistance in Caenorhabditis elegans. - Highlights: • OA extends the lifespan of wild-type Caenorhabditis elegans. • OA improves the stress resistance and reduces the intracellular ROS level in C. elegans. • OA induces lifespan extension may not proceed through the CR mechanism. • OA extends the lifespan in C. elegans is modulated by daf-16.

  19. Oleanolic acid activates daf-16 to increase lifespan in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun, E-mail: lijunzhou@tju.edu.cn

    2015-12-25

    Oleanolic acid (OA) is an active ingredient in natural plants. It has been reported to possess a variety of pharmacological activities, but very little is known about its effects of anti-aging. We investigate here whether OA has an impact on longevity in vivo, and more specifically, we have examined effects of OA on the lifespan and stress tolerance in Caenorhabditis elegans (C. elegans). Our results showed that OA could extend the lifespan, increase its stress resistance and reduce the intracellular reactive oxygen species (ROS) in wild-type worms. Moreover, we have found that OA-induced longevity may not be associated with the calorie restriction (CR) mechanism. Our mechanistic studies using daf-16 loss-of-function mutant strains (GR1307) indicated that the extension of lifespan by OA requires daf-16. In addition, OA treatment could also modulate the nuclear localization, and the quantitative real-time PCR results revealed that up-regulation of daf-16 target genes such as sod-3, hsp-16.2 and ctl-1 could prolong lifespan and increase stress response in C. elegans. This study overall uncovers the longevity effect of OA and its underpinning mechanisms. - Graphical abstract: Oleanolic acid modulates the activity of DAF-16 to promote longevity and increase stress resistance in Caenorhabditis elegans. - Highlights: • OA extends the lifespan of wild-type Caenorhabditis elegans. • OA improves the stress resistance and reduces the intracellular ROS level in C. elegans. • OA induces lifespan extension may not proceed through the CR mechanism. • OA extends the lifespan in C. elegans is modulated by daf-16.

  20. Context-dependent regulation of feeding behaviour by the insulin receptor, DAF-2, in Caenorhabditis elegans.

    Science.gov (United States)

    Dillon, James; Holden-Dye, Lindy; O'Connor, Vincent; Hopper, Neil A

    2016-06-01

    Insulin signalling plays a significant role in both developmental programmes and pathways modulating the neuronal signalling that controls adult behaviour. Here, we have investigated insulin signalling in food-associated behaviour in adult C. elegans by scoring locomotion and feeding on and off bacteria, the worm's food. This analysis used mutants (daf-2, daf-18) of the insulin signalling pathway, and we provide evidence for an acute role for insulin signalling in the adult nervous system distinct from its impact on developmental programmes. Insulin receptor daf-2 mutants move slower than wild type both on and off food and showed impaired locomotory responses to food deprivation. This latter behaviour is manifest as a failure to instigate dispersal following prolonged food deprivation and suggests a role for insulin signalling in this adaptive response. Insulin receptor daf-2 mutants are also deficient in pharyngeal pumping on food and off food. Pharmacological analysis showed the pharynx of daf-2 is selectively compromised in its response to 5-HT compared to the excitatory neuropeptide FLP-17. By comparing the adaptive pharyngeal behaviour in intact worms and isolated pharyngeal preparations, we determined that an insulin-dependent signal extrinsic to the pharyngeal system is involved in feeding adaptation. Hence, we suggest that reactive insulin signalling modulates both locomotory foraging and pharyngeal pumping as the animal adapts to the absence of food. We discuss this in the context of insulin signalling directing a shift in the sensitivity of neurotransmitter systems to regulate the worm's response to changes in food availability in the environment.

  1. DAFS study of site-specific local structure of Mn in manganese ferrite films

    International Nuclear Information System (INIS)

    Kravtsov, E.; Haskel, D.; Cady, A.; Yang, A.; Vittoria, C.; Zuo, X.; Harris, V.G.

    2006-01-01

    Manganese ferrite (MnFe 2 O 4 ) is a well-known magnetic material widely used in electronics for many years. It is well established that its magnetic behavior is strongly influenced by local structural properties of Mn ions, which are distributed between crystallographically inequivalent tetrahedral and octahedral sites in the unit cell. In order to understand and be able to tune properties of these structures, it is necessary to have detailed site-specific structural information on the system. Here we report on the application of diffraction-anomalous fine structure (DAFS) spectroscopy to resolve site-specific Mn local structures in manganese ferrite films. The DAFS measurements were done at undulator beamline 4-ID-D of the Advanced Photon Source at Argonne National Laboratory. The DAFS spectra (Fig. 1) were measured at several Bragg reflections in the vicinity of the Mn absorption K-edge, having probed separately contributions from tetrahedrally and octahedrally coordinated Mn sites. The DAFS data analysis done with an iterative Kramers-Kroenig algorithm made it possible to solve separately the local structure around different inequivalent Mn sites in the unit cell. The reliability of the data treatment was checked carefully, and it was showed that the site-specific structural parameters obtained with DAFS allow us to describe fluorescence EXAFS spectrum measured independently. Fig. 2 shows individual site contributions to the imaginary part of the resonant scattering amplitude obtained from the treatment of the data of Fig. 1. The analysis of the refined site-specific absorption spectra was done using EXAFS methods based on theoretical standards. We provided direct evidence for the tetrahedral Mn-O bond distance being increased relative to the corresponding Fe-O distance in bulk manganese ferrites. The first coordination shell number was found to be reduced significantly for Mn atoms at these sites. This finding is consistent with the well-known tendency of Mn

  2. Site-Directed Mutagenesis Study Revealed Three Important Residues in Hc-DAF-22, a Key Enzyme Regulating Diapause of Haemonchus contortus

    Directory of Open Access Journals (Sweden)

    Yan Huang

    2017-11-01

    Full Text Available Haemonchus contortus (H. contortus is one of the most important parasites of small ruminants, especially goats and sheep. The complex life cycle of this nematode is a main obstacle for the control and prevention of haemonchosis. So far, a special form of arrested development called diapause different from the dauer stage in Caenorhabditis elegans (C. elegans has been found in many parasitic nematodes. In our previous study, we have characterized a novel gene Hc-daf-22 from H. contortus sharing high homology with Ce-daf-22 and functional analysis showed this gene has similar biological function with Ce-daf-22. In this study, Hc-daf-22 mutants were constructed using site-directed mutagenesis, and carried out rescue experiments, RNA interference (RNAi experiments and in vitro enzyme activity analysis with the mutants to further explore the precise function site of Hc-DAF-22. The results showed that Hc-daf-22 mutants could be expressed in the rescued ok693 worms and the expression positions were mainly in the intestine which was identical with that of Hc-daf-22 rescued worms. Through lipid staining we found that Hc-daf-22 could rescue daf-22 mutant (ok693 from the fatty acid metabolism deficiency while Hc-daf-22 mutants failed. Brood size and body length analyses in rescue experiment along with body length and life span analyses in RNAi experiment elucidated that Hc-daf-22 resembled Ce-daf-22 in effecting the development and capacity of C. elegans and mutants impaired the function of Hc-daf-22. Together with the protease activity assay, this research revealed three important active resides 84C/299H/349H in Hc-DAF-22 by site-directed mutagenesis.

  3. Site-Directed Mutagenesis Study Revealed Three Important Residues in Hc-DAF-22, a Key Enzyme Regulating Diapause of Haemonchus contortus.

    Science.gov (United States)

    Huang, Yan; Zheng, Xiuping; Zhang, Hongli; Ding, Haojie; Guo, Xiaolu; Yang, Yi; Chen, Xueqiu; Zhou, Qianjin; Du, Aifang

    2017-01-01

    Haemonchus contortus ( H. contortus ) is one of the most important parasites of small ruminants, especially goats and sheep. The complex life cycle of this nematode is a main obstacle for the control and prevention of haemonchosis. So far, a special form of arrested development called diapause different from the dauer stage in Caenorhabditis elegans ( C. elegans ) has been found in many parasitic nematodes. In our previous study, we have characterized a novel gene Hc-daf-22 from H. contortus sharing high homology with Ce-daf-22 and functional analysis showed this gene has similar biological function with Ce-daf-22 . In this study, Hc-daf-22 mutants were constructed using site-directed mutagenesis, and carried out rescue experiments, RNA interference (RNAi) experiments and in vitro enzyme activity analysis with the mutants to further explore the precise function site of Hc-DAF-22. The results showed that Hc-daf-22 mutants could be expressed in the rescued ok693 worms and the expression positions were mainly in the intestine which was identical with that of Hc-daf-22 rescued worms. Through lipid staining we found that Hc-daf-22 could rescue daf-22 mutant ( ok693 ) from the fatty acid metabolism deficiency while Hc-daf-22 mutants failed. Brood size and body length analyses in rescue experiment along with body length and life span analyses in RNAi experiment elucidated that Hc-daf-22 resembled Ce-daf-22 in effecting the development and capacity of C. elegans and mutants impaired the function of Hc-daf-22 . Together with the protease activity assay, this research revealed three important active resides 84C/299H/349H in Hc-DAF-22 by site-directed mutagenesis.

  4. Kinetic analysis of DAF-FM activation by NO: toward calibration of a NO-sensitive fluorescent dye.

    Science.gov (United States)

    Namin, Shabnam M; Nofallah, Sara; Joshi, Mahesh S; Kavallieratos, Konstantinos; Tsoukias, Nikolaos M

    2013-01-15

    Nitric oxide (NO) research in biomedicine has been hampered by the absence of a method that will allow quantitative measurement of NO in biological tissues with high sensitivity and selectivity, and with adequate spatial and temporal resolution. 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM) is a NO sensitive fluorescence probe that has been used widely for qualitative assessment of cellular NO production. However, calibration of the fluorescent signal and quantification of NO concentration in cells and tissues using fluorescent probes, have provided significant challenge. In this study we utilize a combination of mathematical modeling and experimentation to elucidate the kinetics of NO/DAF-FM reaction in solution. Modeling and experiments suggest that the slope of fluorescent intensity (FI) can be related to NO concentration according to the equation: ddtFI=2αk(1)NO(2)O(2)DAF-FMkNO+DAF-FM where α is a proportionality coefficient that relates FI to unit concentration of activated DAF-FM, k(1) is the NO oxidation rate constant, and k was estimated to be 4.3±0.6. The FI slope exhibits saturation kinetics with DAF-FM concentration. Interestingly, the effective half-maximum constant (EC(50)) increases proportionally to NO concentration. This result is not in agreement with the proposition that N(2)O(3) is the NO oxidation byproduct that activates DAF-FM. Kinetic analysis suggests that the reactive intermediate should exhibit NO-dependent consumption and thus NO(2)() is a more likely candidate. The derived rate law can be used for the calibration of DAF-FM fluorescence and the quantification of NO concentration in biological tissues. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Regulation of lead toxicity by heat shock protein 90 (daf-21) is affected by temperature in Caenorhabditis elegans.

    Science.gov (United States)

    Wang, Yunbiao; Xu, Songbai; Liu, Jing; Zhang, Yanhui; Guo, Tai L

    2014-06-01

    In the nematode Caenorhabditis elegans, stress resistance can be regulated by dauer formation (daf) genes. In the present study, regulation of heavy metal lead (Pb) toxicity by the 90-kDa heat shock proteins (Hsp90; daf-21) was investigated in both wild-type C. elegans and daf-21/Hsp90 mutants by focusing on the effects of varied temperatures below (15°C) or above (25 and 30°C) the presumptive optimum growth temperature (20°C). More acute toxicity of Pb, indicated by the 24-h median lethal concentrations (LC50), was observed in wild-type adults than in the daf-21 mutant adults at 15, 20 and 25°C; however, the daf-21 mutant adults showed more sensitivity at 30°C. Enhanced Pb sensitivity (e.g., decrease LC50) in both types of C. elegans was observed with both increased and decreased temperatures when compared to that at 20°C. Additional examined endpoints included time course of toxicity at LC50s, pharyngeal pumping, reproduction, life span, and Hsp90 expression. Collective results showed that temperatures both above and below 20°C exacerbated Pb toxicity, and that the protein level of daf-21/Hsp90 was one of the most sensitive indicators of Pb toxicity in wild-type C. elegans, while pharyngeal pumping was more Pb sensitive in daf-21 mutants. Therefore, the expression of daf-21/Hsp90 has apparent utility for the prediction and assessment of Pb-induced toxicity in nematodes. Further, the stress responses related to Hsp90 expression in C. elegans may have considerable potential as sensitive biomarkers for the monitoring of environmental Pb contamination. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Isoamyl alcohol odor promotes longevity and stress tolerance via DAF-16 in Caenorhabditis elegans.

    Science.gov (United States)

    Kurino, Chiho; Furuhashi, Tsubasa; Sudoh, Kaori; Sakamoto, Kazuichi

    2017-04-01

    The possibility that odor plays a role in lifespan regulation through effects on the nervous system is indicated by research on Caenorhabditis elegans. In fact, ablation of AWA and AWC, which are suggested as olfactory neurons, has been shown to extend lifespan via DAF-16, a homolog of FoxO. However, the effects of odor stimuli on the lifespan still remain unclear. Thus, we here aimed to clarify the effect of attractive and repulsive odors on longevity and stress tolerance in C. elegans and to analyze the pathways thereof. We used isoamyl alcohol as an attractive odor, and acetic acid as a repellent component, as identified by chemotaxis assay. We found that isoamyl alcohol stimulus promoted longevity in a DAF-16-dependent manner. On the other hand, acetic acid stimulus promoted thermotolerance through mechanisms independent of DAF-16. Above all, our results indicate that odor stimuli affect the lifespan and stress tolerance of C. elegans, with attractive and repulsive odors exerting their effects through different mechanisms, and that longevity is induced by both activation and inactivation of olfactory neurons. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Oleanolic acid activates daf-16 to increase lifespan in Caenorhabditis elegans.

    Science.gov (United States)

    Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun

    2015-12-25

    Oleanolic acid (OA) is an active ingredient in natural plants. It has been reported to possess a variety of pharmacological activities, but very little is known about its effects of anti-aging. We investigate here whether OA has an impact on longevity in vivo, and more specifically, we have examined effects of OA on the lifespan and stress tolerance in Caenorhabditis elegans (C. elegans). Our results showed that OA could extend the lifespan, increase its stress resistance and reduce the intracellular reactive oxygen species (ROS) in wild-type worms. Moreover, we have found that OA-induced longevity may not be associated with the calorie restriction (CR) mechanism. Our mechanistic studies using daf-16 loss-of-function mutant strains (GR1307) indicated that the extension of lifespan by OA requires daf-16. In addition, OA treatment could also modulate the nuclear localization, and the quantitative real-time PCR results revealed that up-regulation of daf-16 target genes such as sod-3, hsp-16.2 and ctl-1 could prolong lifespan and increase stress response in C. elegans. This study overall uncovers the longevity effect of OA and its underpinning mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. A study on some welfare-related parameters of hDAF transgenic pigs when compared with their conventional close relatives.

    Science.gov (United States)

    Martelli, G; Sardi, L; Stancampiano, L; Govoni, N; Zannoni, A; Nannoni, E; Forni, M; Bacci, M L

    2014-05-01

    Pigs are increasingly used in medical research as transgenic laboratory animals; however, little knowledge is presently available concerning their welfare assessment. The aim of the present study was to investigate some welfare-related parameters of transgenic pigs intended for xenotrasplantation (human decay-accelerating factor (hDAF)) when compared with their conventional (i.e. not transgenic) close relatives (full sibs and half sibs). A total of 14 Large White female transgenic pigs and 10 female non-transgenic (conventional) pigs from four litters were used. All pigs were from the same conventional boar, donor of the semen treated for sperm-mediated gene transfer. During the experiment, BW ranged from 50 to about 80 kg and pigs were weighed at the beginning and at the end of the experiment. Animals were subjected to a set of behavioural tests: a human approach test (HAT), a novel object test (NOT) and an open-door test (ODT). Food preferences were tested through the offer of different foods (banana, apple, carrot, cracker and lemon). During a 4-day period, pigs were diurnally videotaped to study the prevalence of the different behaviours and social interactions (aggressive and non-aggressive interactions). At the end of the trial, cortisol level had been assessed on bristles. No significant differences (P>0.05) were observed between hDAF transgenic and conventional pigs with respect to growth traits, reactivity towards unexpected situations (HAT, NOT, ODT), food preferences, main behavioural traits, social interactions and hair cortisol.

  9. Emodin extends lifespan of Caenorhabditis elegans through insulin/IGF-1 signaling pathway depending on DAF-16 and SIR-2.1.

    Science.gov (United States)

    Zhao, Xuan; Lu, Lulu; Qi, Yonghao; Li, Miao; Zhou, Lijun

    2017-10-01

    The naturally occurring anthraquinone emodin has been serving primarily as an anti-bacterial and anti-inflammatory agent. However, little is known about its potential on anti-aging. This investigation examined the effect of emodin on lifespan and focused on its physiological molecular mechanisms in vivo. Using Caenorhabditis elegans (C. elegans) as an animal model, we found emodin could extend lifespan of worms and improve their antioxidant capacity. Our mechanistic studies revealed that emodin might function via insulin/IGF-1 signaling (IIS) pathway involving, specifically the core transcription factor DAF-16. Quantitative RT-PCR results illustrated that emodin up-regulated transcription of DAF-16 target genes which express antioxidants to promote antioxidant capacity and lifespan of worms. In addition, attenuated effect in sir-2.1 mutants suggests that emodin likely functioned in a SIR-2.1-dependent manner. Our study uncovers a novel role of emodin in prolonging lifespan and supports the understanding of emodin being a beneficial dietary supplement.

  10. Characterization of PUD-1 and PUD-2, two proteins up-regulated in a long-lived daf-2 mutant.

    Science.gov (United States)

    Ding, Yue-He; Du, Yun-Guang; Luo, Shukun; Li, Yu-Xin; Li, Tie-Mei; Yoshina, Sawako; Wang, Xing; Klage, Karsten; Mitani, Shohei; Ye, Keqiong; Dong, Meng-Qiu

    2013-01-01

    C. elegans PUD-1 and PUD-2, two proteins up-regulated in daf-2(loss-of-function) (PUD), are homologous 17-kD proteins with a large abundance increase in long-lived daf-2 mutant animals of reduced insulin signaling. In this study, we show that both PUD-1 and PUD-2 are abundantly expressed in the intestine and hypodermis, and form a heterodimer. We have solved their crystal structure to 1.9-Å resolution and found that both proteins adopt similar β-sandwich folds in the V-shaped dimer. In contrast, their homologs PUD-3, PUD-4, PUDL-1 and PUDL-2 are all monomeric proteins with distinct expression patterns in C. elegans. Thus, the PUD-1/PUD-2 heterodimer probably has a function distinct from their family members. Neither overexpression nor deletion of pud-1 and pud-2 affected the lifespan of WT or daf-2 mutant animals, suggesting that their induction in daf-2 worms does not contribute to longevity. Curiously, deletion of pud-1 and pud-2 was associated with a protective effect against paralysis induced by the amyloid β-peptide (1-42), which further enhanced the protection conferred by daf-2(RNAi) against Aβ.

  11. The thioredoxin TRX-1 modulates the function of the insulin-like neuropeptide DAF-28 during dauer formation in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Juan Carlos Fierro-González

    2011-01-01

    Full Text Available Thioredoxins comprise a conserved family of redox regulators involved in many biological processes, including stress resistance and aging. We report that the C. elegans thioredoxin TRX-1 acts in ASJ head sensory neurons as a novel modulator of the insulin-like neuropeptide DAF-28 during dauer formation. We show that increased formation of stress-resistant, long-lived dauer larvae in mutants for the gene encoding the insulin-like neuropeptide DAF-28 requires TRX-1 acting in ASJ neurons, upstream of the insulin-like receptor DAF-2. Genetic rescue experiments demonstrate that redox-independent functions of TRX-1 specifically in ASJ neurons are needed for the dauer formation constitutive (Daf-c phenotype of daf-28 mutants. GFP reporters of trx-1 and daf-28 show opposing expression patterns in dauers (i.e. trx-1 is up-regulated and daf-28 is down-regulated, an effect that is not observed in growing L2/L3 larvae. In addition, functional TRX-1 is required for the down-regulation of a GFP reporter of daf-28 during dauer formation, a process that is likely subject to DAF-28-mediated feedback regulation. Our findings demonstrate that TRX-1 modulates DAF-28 signaling by contributing to the down-regulation of daf-28 expression during dauer formation. We propose that TRX-1 acts as a fluctuating neuronal signaling modulator within ASJ neurons to monitor the adjustment of neuropeptide expression, including insulin-like proteins, during dauer formation in response to adverse environmental conditions.

  12. The thioredoxin TRX-1 modulates the function of the insulin-like neuropeptide DAF-28 during dauer formation in Caenorhabditis elegans.

    Science.gov (United States)

    Fierro-González, Juan Carlos; Cornils, Astrid; Alcedo, Joy; Miranda-Vizuete, Antonio; Swoboda, Peter

    2011-01-27

    Thioredoxins comprise a conserved family of redox regulators involved in many biological processes, including stress resistance and aging. We report that the C. elegans thioredoxin TRX-1 acts in ASJ head sensory neurons as a novel modulator of the insulin-like neuropeptide DAF-28 during dauer formation. We show that increased formation of stress-resistant, long-lived dauer larvae in mutants for the gene encoding the insulin-like neuropeptide DAF-28 requires TRX-1 acting in ASJ neurons, upstream of the insulin-like receptor DAF-2. Genetic rescue experiments demonstrate that redox-independent functions of TRX-1 specifically in ASJ neurons are needed for the dauer formation constitutive (Daf-c) phenotype of daf-28 mutants. GFP reporters of trx-1 and daf-28 show opposing expression patterns in dauers (i.e. trx-1 is up-regulated and daf-28 is down-regulated), an effect that is not observed in growing L2/L3 larvae. In addition, functional TRX-1 is required for the down-regulation of a GFP reporter of daf-28 during dauer formation, a process that is likely subject to DAF-28-mediated feedback regulation. Our findings demonstrate that TRX-1 modulates DAF-28 signaling by contributing to the down-regulation of daf-28 expression during dauer formation. We propose that TRX-1 acts as a fluctuating neuronal signaling modulator within ASJ neurons to monitor the adjustment of neuropeptide expression, including insulin-like proteins, during dauer formation in response to adverse environmental conditions.

  13. Cooperation of decay-accelerating factor and membrane cofactor protein in regulating survival of human cervical cancer cells

    International Nuclear Information System (INIS)

    Gao, Ling-Juan; Guo, Shu-Yu; Cai, You-Qun; Gu, Ping-Qing; Su, Ya-Juan; Gong, Hui; Liu, Yun; Chen, Chen

    2009-01-01

    Decay-accelerating factor (DAF) and membrane cofactor protein (MCP) are the key molecules involved in cell protection against autologus complement, which restricts the action of complement at critical stages of the cascade reaction. The cooperative effect of DAF and MCP on the survival of human cervical cancer cell (ME180) has not been demonstrated. In this study we applied, for the first time, short hairpin RNA (shRNA) to knock down the expression of the DAF and MCP with the aim of exploiting complement more effectively for tumor cell damage. Meanwhile, we investigated the cooperative effects of DAF and MCP on the viability and migration, moreover the proliferation of ME180 cell. The results showed that shRNA inhibition of DAF and MCP expression enhanced complement-dependent cytolysis (CDC) up to 39% for MCP and up to 36% for DAF, and the combined inhibition of both regulators yielded further additive effects in ME180 cells. Thus, the activities of DAF and MCP, when present together, are greater than the sum of the two protein individually. These data indicated that combined DAF and MCP shRNA described in this study may offer an additional alternative to improve the efficacy of antibody-and complement-based cancer immunotherapy

  14. Caenorhabditis elegans DAF-2 as a Model for Human Insulin Receptoropathies

    Directory of Open Access Journals (Sweden)

    David A. Bulger

    2017-01-01

    Full Text Available Human exome sequencing has dramatically increased the rate of identification of disease-associated polymorphisms. However, examining the functional consequences of those variants has created an analytic bottleneck. Insulin-like signaling in Caenorhabditis elegans has long provided a model to assess consequences of human insulin signaling mutations, but this has not been evaluated in the context of current genetic tools. We have exploited strains derived from the Million Mutation Project (MMP and gene editing to explore further the evolutionary relationships and conservation between the human and C. elegans insulin receptors. Of 40 MMP alleles analyzed in the C. elegans insulin-like receptor gene DAF-2, 35 exhibited insulin-like signaling indistinguishable from wild-type animals, indicating tolerated mutations. Five MMP alleles proved to be novel dauer-enhancing mutations, including one new allele in the previously uncharacterized C-terminus of DAF-2. CRISPR-Cas9 genome editing was used to confirm the phenotypic consequence of six of these DAF-2 mutations and to replicate an allelic series of known human disease mutations in a highly conserved tyrosine kinase active site residue, demonstrating the utility of C. elegans for directly modeling human disease. Our results illustrate the challenges associated with prediction of the phenotypic consequences of amino acid substitutions, the value of assaying mutant isoform function in vivo, and how recently developed tools and resources afford the opportunity to expand our understanding even of highly conserved regulatory modules such as insulin signaling. This approach may prove generally useful for modeling phenotypic consequences of candidate human pathogenic mutations in conserved signaling and developmental pathways.

  15. Caenorhabditis elegans DAF-2 as a Model for Human Insulin Receptoropathies.

    Science.gov (United States)

    Bulger, David A; Fukushige, Tetsunari; Yun, Sijung; Semple, Robert K; Hanover, John A; Krause, Michael W

    2017-01-05

    Human exome sequencing has dramatically increased the rate of identification of disease-associated polymorphisms. However, examining the functional consequences of those variants has created an analytic bottleneck. Insulin-like signaling in Caenorhabditis elegans has long provided a model to assess consequences of human insulin signaling mutations, but this has not been evaluated in the context of current genetic tools. We have exploited strains derived from the Million Mutation Project (MMP) and gene editing to explore further the evolutionary relationships and conservation between the human and C. elegans insulin receptors. Of 40 MMP alleles analyzed in the C. elegans insulin-like receptor gene DAF-2, 35 exhibited insulin-like signaling indistinguishable from wild-type animals, indicating tolerated mutations. Five MMP alleles proved to be novel dauer-enhancing mutations, including one new allele in the previously uncharacterized C-terminus of DAF-2 CRISPR-Cas9 genome editing was used to confirm the phenotypic consequence of six of these DAF-2 mutations and to replicate an allelic series of known human disease mutations in a highly conserved tyrosine kinase active site residue, demonstrating the utility of C. elegans for directly modeling human disease. Our results illustrate the challenges associated with prediction of the phenotypic consequences of amino acid substitutions, the value of assaying mutant isoform function in vivo, and how recently developed tools and resources afford the opportunity to expand our understanding even of highly conserved regulatory modules such as insulin signaling. This approach may prove generally useful for modeling phenotypic consequences of candidate human pathogenic mutations in conserved signaling and developmental pathways. Copyright © 2017 Bulger et al.

  16. Baseline tests of the C. H. Waterman DAF electric passenger vehicle

    Science.gov (United States)

    Sargent, N. B.; Maslowski, E. A.; Soltis, R. F.; Schuh, R. M.

    1977-01-01

    An electric vehicle was tested as part of an Energy Research Development Administration (ERDA) project to characterize the state-of-the-art of electric vehicles. The Waterman vehicle performance test results are presented in this report. The vehicle is a converted four-passenger DAF 46 sedan. It is powered by sixteen 6-volt traction batteries through a three-step contactor controller actuated by a foot throttle to change the voltage applied to the 6.7 kW motor. The braking system is a conventional hydraulic braking system.

  17. Central nervous system promotes thermotolerance via FoxO/DAF-16 activation through octopamine and acetylcholine signaling in Caenorhabditis elegans.

    Science.gov (United States)

    Furuhashi, Tsubasa; Sakamoto, Kazuichi

    2016-03-25

    The autonomic nervous system (ANS) responds to many kinds of stressors to maintain homeostasis. Although the ANS is believed to regulate stress tolerance, the exact mechanism underlying this is not well understood. To understand this, we focused on longevity genes, which have functions such as lifespan extension and promotion of stress tolerance. To understand the relationship between ANS and longevity genes, we analyzed stress tolerance of Caenorhabditis elegans treated with octopamine, which has an affinity to noradrenaline in insects, and acetylcholine. Octopamine and acetylcholine did not show resistance against H2O2, but the neurotransmitters promoted thermotolerance via DAF-16. However, chronic treatment with octopamine and acetylcholine did not extend the lifespan, although DAF-16 plays an important role in longevity. In conclusion, our results show that octopamine and acetylcholine activate DAF-16 in response to stress, but chronic induction of octopamine and acetylcholine is not beneficial for increasing longevity. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Dafachronic acid inhibits C. elegans germ cell proliferation in a DAF-12-dependent manner.

    Science.gov (United States)

    Mukherjee, Madhumati; Chaudhari, Snehal N; Balachandran, Riju S; Vagasi, Alexandra S; Kipreos, Edward T

    2017-12-15

    Dafachronic acid (DA) is a bile acid-like steroid hormone that regulates dauer formation, heterochrony, and lifespan in C. elegans. Here, we describe that DA is an inhibitor of C. elegans germ stem cell proliferation in adult hermaphrodites. Using a C. elegans germ cell primary culture system, we show that DA inhibits the proliferation of germ cells in vitro. Exogenous DA reduces the frequency of large tumors in adult tumorous germline mutants and decreases the proliferation of wild-type germ stem cells in adult hermaphrodites. In contrast, DA has no appreciable effect on the proliferation of larval-stage germ cells in wild type. The inhibition of adult germ cell proliferation by DA requires its canonical receptor DAF-12. Blocking DA production by inactivating the cytochrome P450 DAF-9 increases germ cell proliferation in wild-type adult hermaphrodites and the frequency of large tumors in germline tumorous mutants, suggesting that DA inhibits the rate of germ cell proliferation under normal growth conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Diosgenin a phytosterol substitute for cholesterol, prolongs the lifespan and mitigates glucose toxicity via DAF-16/FOXO and GST-4 in Caenorhabditis elegans.

    Science.gov (United States)

    Shanmugam, Govindan; Mohankumar, Amirthalingam; Kalaiselvi, Duraisamy; Nivitha, Sundararaj; Murugesh, Easwaran; Shanmughavel, Piramanayagam; Sundararaj, Palanisamy

    2017-11-01

    Caenorhabditis elegans is a sterol auxotroph requires minute amount of exogenous sterol for their growth and development. To culture the C. elegans, cholesterol was given as sterol molecule to maintain the optimum survival of worms. Diosgenin (DG), a plant derived steroidal saponin, structurally similar to cholesterol has been used as a precursor for the synthesis of steroidal hormones. In this study, worms were cultured with cholesterol (Cho + ) and cholesterol-free (Cho - ) medium with DG (5, 10 and 50μg/mL) at 20°C. It was observed that worms cultured in (Cho - ) exhibits late egg production, reduced lipid level and short lifespan, while addition of DG overcomes all defective facts. Combinations of both cholesterol and DG further extend the lifespan (20.8%), hinder lipid level and resistance to oxidative, thermal and high glucose stress. The intracellular ROS quantification was done by flouroscenic probe H2DCF-DA and confirmed that DG had significantly reduced ROS level (35.85%). Increased lifespan of worms were observed in the medium treated with DG which activates the nuclear translocation of DAF-16/FOXO transcription factor, followed by downstream antioxidant gene sod-3 as evidenced by GFP tagged strain. The expression of Phase II detoxification enzyme GST-4 significantly (pdaf-16, skn-1, and eat-2. These studies have proved that DG is a sterol source to worms and modulate the DAF-16, SOD-3 and GST-4 expression levels to extend the lifespan of worms. The present study has also highlighted the use of phytosterols as an alternative to cholesterol. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Comparison between XAS, AWAXS and DAFS applied to nanometer scale supported metallic clusters. Pt.1; monometallic clusters

    International Nuclear Information System (INIS)

    Bazin, D.C.; Sayers, D.A.

    1993-01-01

    The structural information found using three techniques related to synchrotron radiation are compared. XAS (X-ray Absorption Spectroscopy), AWAXS (Anomalous Wide Angle X-ray Scattering) and DAFS (Diffraction Anomalous Fine Structure) are applied to nanometer scale metallic clusters. (author)

  1. Comparison between XAS, AWAXS and DAFS applied to nanometer scale supported metallic clusters. Pt.2; bimetallic clusters

    International Nuclear Information System (INIS)

    Bazin, D.; Sayers, D.

    1993-01-01

    The structural information obtained using three techniques related to synchrotron radiation are compared. XAS (X-ray Absorption Spectroscopy), AWAXS (Anomalous Wide Angle X-ray Scattering) and DAFS (Diffraction Anomalous Fine Structure) are applied to the study of nanometer scale bimetallic clusters. (author)

  2. DAF-2 and ERK Couple Nutrient Availability to Meiotic Progression during Caenorhabditis elegans Oogenesis

    Science.gov (United States)

    Lopez, Andrew L.; Chen, Jessica; Joo, Hyoe-Jin; Drake, Melanie; Shidate, Miri; Kseib, Cedric; Arur, Swathi

    2013-01-01

    Coupling the production of mature gametes and fertilized zygotes to favorable nutritional conditions improves reproductive success. In invertebrates, the proliferation of female germ line stem cells is regulated by nutritional status. But, in mammals the number of female germ line stem cells is set early in development, with oocytes progressing through meiosis later in life. Mechanisms that couple later steps of oogenesis to environmental conditions remain largely undefined. We show that in the presence of food, the DAF-2 insulin-like receptor signals through the RAS-ERK pathway to drive meiotic prophase I progression and oogenesis; in the absence of food, the resultant inactivation of insulin-like signaling leads to downregulation of RAS-ERK pathway, and oogenesis is stalled. Thus, the insulin-like signaling pathway couples nutrient sensing to meiotic I progression and oocyte production in C. elegans, ensuring that oocytes are only produced under conditions favorable for the survival of the resulting zygotes. PMID:24120884

  3. Gαo and Gαq regulate the expression of daf-7, a TGFβ-like gene, in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Edith M Myers

    Full Text Available Caenorhabditis elegans enter an alternate developmental stage called dauer in unfavorable conditions such as starvation, overcrowding, or high temperature. Several evolutionarily conserved signaling pathways control dauer formation. DAF-7/TGFβ and serotonin, important ligands in these signaling pathways, affect not only dauer formation, but also the expression of one another. The heterotrimeric G proteins GOA-1 (Gα(o and EGL-30 (Gα(q mediate serotonin signaling as well as serotonin biosynthesis in C. elegans. It is not known whether GOA-1 or EGL-30 also affect dauer formation and/or daf-7 expression, which are both modulated in part by serotonin. The purpose of this study is to better understand the relationship between proteins important for neuronal signaling and developmental plasticity in both C. elegans and humans. Using promoter-GFP transgenic worms, it was determined that both goa-1 and egl-30 regulate daf-7 expression during larval development. In addition, the normal daf-7 response to high temperature or starvation was altered in goa-1 and egl-30 mutants. Despite the effect of goa-1 and egl-30 mutations on daf-7 expression in various environmental conditions, there was no effect of the mutations on dauer formation. This paper provides evidence that while goa-1 and egl-30 are important for normal daf-7 expression, mutations in these genes are not sufficient to disrupt dauer formation.

  4. DAF-2/insulin-like signaling in C. elegans modifies effects of dietary restriction and nutrient stress on aging, stress and growth.

    Directory of Open Access Journals (Sweden)

    Wendy B Iser

    2007-11-01

    Full Text Available Dietary restriction (DR and reduced insulin/IGF-I-like signaling (IIS are two regimens that promote longevity in a variety of organisms. Genetic analysis in C. elegans nematodes has shown that DR and IIS couple to distinct cellular signaling pathways. However, it is not known whether these pathways ultimately converge on overlapping or distinct targets to extend lifespan.We investigated this question by examining additional effects of DR in wildtype animals and in daf-2 mutants with either moderate or severe IIS deficits. Surprisingly, DR and IIS had opposing effects on these physiological processes. First, DR induced a stress-related change in intestinal vesicle trafficking, termed the FIRE response, which was suppressed in daf-2 mutants. Second, DR did not strongly affect expression of a daf-2- and stress-responsive transcriptional reporter. Finally, DR-related growth impairment was suppressed in daf-2 mutants.These findings reveal that an important biological function of DAF-2/IIS is to enhance growth and survival under nutrient-limited conditions. However, we also discovered that levels of DAF-2 pathway activity modified the effects of DR on longevity. Thus, while DR and IIS clearly affect lifespan through independent targets, there may also be some prolongevity targets that are convergently regulated by these pathways.

  5. DAF-2/insulin-like signaling in C. elegans modifies effects of dietary restriction and nutrient stress on aging, stress and growth.

    Science.gov (United States)

    Iser, Wendy B; Wolkow, Catherine A

    2007-11-28

    Dietary restriction (DR) and reduced insulin/IGF-I-like signaling (IIS) are two regimens that promote longevity in a variety of organisms. Genetic analysis in C. elegans nematodes has shown that DR and IIS couple to distinct cellular signaling pathways. However, it is not known whether these pathways ultimately converge on overlapping or distinct targets to extend lifespan. We investigated this question by examining additional effects of DR in wildtype animals and in daf-2 mutants with either moderate or severe IIS deficits. Surprisingly, DR and IIS had opposing effects on these physiological processes. First, DR induced a stress-related change in intestinal vesicle trafficking, termed the FIRE response, which was suppressed in daf-2 mutants. Second, DR did not strongly affect expression of a daf-2- and stress-responsive transcriptional reporter. Finally, DR-related growth impairment was suppressed in daf-2 mutants. These findings reveal that an important biological function of DAF-2/IIS is to enhance growth and survival under nutrient-limited conditions. However, we also discovered that levels of DAF-2 pathway activity modified the effects of DR on longevity. Thus, while DR and IIS clearly affect lifespan through independent targets, there may also be some prolongevity targets that are convergently regulated by these pathways.

  6. Comparative metabolomics reveals endogenous ligands of DAF-12, a nuclear hormone receptor regulating C. elegans development and lifespan

    Science.gov (United States)

    Mahanti, Parag; Bose, Neelanjan; Bethke, Axel; Judkins, Joshua C.; Wollam, Joshua; Dumas, Kathleen J.; Zimmerman, Anna M.; Campbell, Sydney L.; Hu, Patrick J.; Antebi, Adam; Schroeder, Frank C.

    2014-01-01

    SUMMARY Small-molecule ligands of nuclear hormone receptors (NHRs) govern the transcriptional regulation of metazoan development, cell differentiation, and metabolism. However, the physiological ligands of many NHRs remain poorly characterized primarily due to lack of robust analytical techniques. Using comparative metabolomics, we identified endogenous steroids that act as ligands of the C. elegans NHR, DAF-12, a vitamin-D and liver-X receptor homolog regulating larval development, fat metabolism, and lifespan. The identified molecules feature unexpected chemical modifications and include only one of two DAF-12 ligands reported earlier, necessitating a revision of previously proposed ligand biosynthetic pathways. We further show that ligand profiles are regulated by a complex enzymatic network including the Rieske oxygenase DAF-36, the short-chain dehydrogenase DHS-16, and the hydroxysteroid dehydrogenase, HSD-1. Our results demonstrate the advantages of comparative metabolomics over traditional candidate-based approaches and provide a blueprint for the identification of ligands for other C. elegans and mammalian NHRs. PMID:24411940

  7. Royal jelly promotes DAF-16-mediated proteostasis to tolerate β-amyloid toxicity in C. elegans model of Alzheimer's disease.

    Science.gov (United States)

    Wang, Xiaoxia; Cao, Min; Dong, Yuqing

    2016-08-23

    Numerous studies have demonstrated that dietary intervention may promote health and help prevent Alzheimer's disease (AD). We recently reported that bee products of royal jelly (RJ) and enzyme-treated royal jelly (eRJ) were potent to promote healthy aging in C. elegans. Here, we examined whether RJ/eRJ consumption may benefit to mitigate the AD symptom in the disease model of C. elegans. Our results showed that RJ/eRJ supplementation significantly delayed the body paralysis in AD worms, suggesting the β-amyloid (Aβ) toxicity attenuation effects of RJ/eRJ. Genetic analyses suggested that RJ/eRJ-mediated alleviation of Aβ toxicity in AD worms required DAF-16, rather than HSF-1 and SKN-1, in an insulin/IGF signaling dependent manner. Moreover, RJ/eRJ modulated the transactivity of DAF-16 and dramatically improved the protein solubility in aged worms. Given protein solubility is a hallmark of healthy proteostasis, our findings demonstrated that RJ/eRJ supplementation improved proteostasis, and this promotion depended on the transactivity of DAF-16. Collectively, the present study not only elucidated the possible anti-AD mechanism of RJ/eRJ, but also provided evidence from a practical point of view to shed light on the extensive correlation of proteostasis and the prevention of neurodegenerative disorders.

  8. DAF: differential ACE filtering image quality assessment by automatic color equalization

    Science.gov (United States)

    Ouni, S.; Chambah, M.; Saint-Jean, C.; Rizzi, A.

    2008-01-01

    Ideally, a quality assessment system would perceive and measure image or video impairments just like a human being. But in reality, objective quality metrics do not necessarily correlate well with perceived quality [1]. Plus, some measures assume that there exists a reference in the form of an "original" to compare to, which prevents their usage in digital restoration field, where often there is no reference to compare to. That is why subjective evaluation is the most used and most efficient approach up to now. But subjective assessment is expensive, time consuming and does not respond, hence, to the economic requirements [2,3]. Thus, reliable automatic methods for visual quality assessment are needed in the field of digital film restoration. The ACE method, for Automatic Color Equalization [4,6], is an algorithm for digital images unsupervised enhancement. It is based on a new computational approach that tries to model the perceptual response of our vision system merging the Gray World and White Patch equalization mechanisms in a global and local way. Like our vision system ACE is able to adapt to widely varying lighting conditions, and to extract visual information from the environment efficaciously. Moreover ACE can be run in an unsupervised manner. Hence it is very useful as a digital film restoration tool since no a priori information is available. In this paper we deepen the investigation of using the ACE algorithm as a basis for a reference free image quality evaluation. This new metric called DAF for Differential ACE Filtering [7] is an objective quality measure that can be used in several image restoration and image quality assessment systems. In this paper, we compare on different image databases, the results obtained with DAF and with some subjective image quality assessments (Mean Opinion Score MOS as measure of perceived image quality). We study also the correlation between objective measure and MOS. In our experiments, we have used for the first image

  9. Decay-accelerating factor 1 deficiency exacerbates Trypanosoma cruzi-induced murine chronic myositis.

    Science.gov (United States)

    Solana, María E; Ferrer, María F; Novoa, María Mercedes; Song, Wen-Chao; Gómez, Ricardo M

    2012-10-01

    Murine infection with Trypanosoma cruzi (Tc) has been used to study the role of T-cells in the pathogenesis of human inflammatory idiopathic myositis. Absence of decay-accelerating factor 1 (Daf1) has been shown to enhance murine T-cell responses and autoimmunity. To determine whether Daf1 deficiency can exacerbate Tc-induced myositis, C57BL/6 DAF(+/+) and DAF(-/-) mice were inoculated with 5 × 10(4) trypomastigotes, and their morbidity, parasitemia, parasite burden, histopathology, and T-cell expansion were studied in the acute and chronic stages. DAF(-/-) mice had lower parasitemia and parasite burden but higher morbidity, muscle histopathology, and increased number of CD44(+) (activated/memory phenotype) splenic CD4(+) and CD8(+) T-cells. An enhanced CD8(+) T-cell immune-specific response may explain the lower parasitemia and parasite burden levels and the increase in histopathological lesions. We propose that Tc-inoculated DAF(-/-) mice are a useful model to study T-cell mediated immunity in skeletal muscle tissues. Copyright © 2012 Wiley Periodicals, Inc.

  10. Muscle-Specific Histone H3K36 Dimethyltransferase SET-18 Shortens Lifespan of Caenorhabditis elegans by Repressing daf-16a Expression

    Directory of Open Access Journals (Sweden)

    Liangping Su

    2018-03-01

    Full Text Available Mounting evidence shows that histone methylation, a typical epigenetic mark, is crucial for gene expression regulation during aging. Decreased trimethylation of Lys 36 on histone H3 (H3K36me3 in worms and yeast is reported to shorten lifespan. The function of H3K36me2 in aging remains unclear. In this study, we identified Caenorhabditis elegans SET-18 as a histone H3K36 dimethyltransferase. SET-18 deletion extended lifespan and increased oxidative stress resistance, dependent on daf-16 activity in the insulin/IGF pathway. In set-18 mutants, transcription of daf-16 isoform a (daf-16a was specifically upregulated. Accordingly, a decrease in H3K36me2 on daf-16a promoter was observed. Muscle-specific expression of SET-18 increased in aged worms (day 7 and day 11, attributable to elevation of global H3K36me2 and inhibition of daf-16a expression. Consequently, longevity was shortened. These findings suggested that chromatic repression mediated by tissue-specific H3K36 dimethyltransferase might be detrimental to lifespan and may have implications in human age-related diseases.

  11. Muscle-Specific Histone H3K36 Dimethyltransferase SET-18 Shortens Lifespan of Caenorhabditis elegans by Repressing daf-16a Expression.

    Science.gov (United States)

    Su, Liangping; Li, Hongyuan; Huang, Cheng; Zhao, Tingting; Zhang, Yongjun; Ba, Xueqing; Li, Zhongwei; Zhang, Yu; Huang, Baiqu; Lu, Jun; Zhao, Yanmei; Li, Xiaoxue

    2018-03-06

    Mounting evidence shows that histone methylation, a typical epigenetic mark, is crucial for gene expression regulation during aging. Decreased trimethylation of Lys 36 on histone H3 (H3K36me3) in worms and yeast is reported to shorten lifespan. The function of H3K36me2 in aging remains unclear. In this study, we identified Caenorhabditis elegans SET-18 as a histone H3K36 dimethyltransferase. SET-18 deletion extended lifespan and increased oxidative stress resistance, dependent on daf-16 activity in the insulin/IGF pathway. In set-18 mutants, transcription of daf-16 isoform a (daf-16a) was specifically upregulated. Accordingly, a decrease in H3K36me2 on daf-16a promoter was observed. Muscle-specific expression of SET-18 increased in aged worms (day 7 and day 11), attributable to elevation of global H3K36me2 and inhibition of daf-16a expression. Consequently, longevity was shortened. These findings suggested that chromatic repression mediated by tissue-specific H3K36 dimethyltransferase might be detrimental to lifespan and may have implications in human age-related diseases. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  12. Effects of non-latching blast valves on the source term and consequences of the design-basis accidents in the Device Assembly Facility (DAF)

    International Nuclear Information System (INIS)

    Nguyen, D.H.

    1993-08-01

    The analysis of the Design-Basis Accidents (DBA) involving high explosives (HE) and Plutonium (Pu) in the assembly cell of the Device Assembly Facility (DAF), which was completed earlier, assumed latching blast valves in the ventilation system of the assembly cell. Latching valves effectively sealed a release path through the ventilation duct system. However, the blast valves in the assembly cell, as constructed are actually non-latching valves, and would reopen when the gas pressure drops to 0.5 psi above one atmosphere. Because the reopening of the blast valves provides an additional release path to the environment, and affects the material transport from the assembly cell to other DAF buildings, the DOE/NV DAF management has decided to support an additional analysis of the DAF's DBA to account for the effects of non-latching valves. Three cases were considered in the DAF's DBA, depending on the amount of HE and Pu involved, as follows: Case 1 -- 423 number-sign HE, 16 kg Pu; Case 2 -- 150 number-sign HE 10 kg Pu; Case 3 -- 55 number-sign HE 5 kg Pu. The results of the analysis with non-latching valves are summarized

  13. Molecular characterisation of Colombian yam germplasm by "DNA amplification fingerprinting (DAF" in radioactivo conditions

    Directory of Open Access Journals (Sweden)

    Silvia L. Bustamante

    2003-07-01

    Full Text Available Samples from the Universidad de Córdoba's yam collection (Dioscorea spp. and others originating from IITA (International Institute of Tropical Agriculture, Ibadan, Nigeria were molecularly characterised to complement existing information about them. The yam (Diosocorea spp. represents a basic crop for small-scale farmers on the Colombian Atlantic Coast who sow around 20,000 hectares per year. Even though they are dioecious species, only one sex is represented in Colombia; it must also be stated that climatic conditions are not propitious for its flowering. This situation has caused difficulty for work in yam breeding. The yam species and varieties used in the Colombian ABP (Agricultural Biotechnology Programme have been molecularly characterised by AFLPs in a previous publication describing a preliminary study emerging from the need to broaden the characterisation of those accessions kept at the Universidad de Córdoba. Comparisons have also been done with some African accessions donated by IITA. In this article, samples were molecularly characterised by another fingerprinting technique, the DAF technique (DNA Amplification Fingerprinting based on PCR, using random oligonucleotides for generating characteristic band patterns from each individual. The results showed 0.0413 population diversity with 0.9587 average similarity, indicating that the yam collection studied had very little genetic diversity and, probably, this could be why the crop is vulnerable to plagues and diseases, as happened at the end of the 1980s when anthracnose practically devastated the crop on the Colombian Atlantic coast. Similarity was also found between those Colombian and African samples analysed, agreeing with low diversity and less distance between common ancestors. The molecular results suggest the need for using other molecular techniques having a greater power of discrimination and also the need to broaden the genetic diversity in yam crops for providing greater

  14. Stable thermophilic anaerobic digestion of dissolved air flotation (DAF) sludge by co-digestion with swine manure.

    Science.gov (United States)

    Creamer, K S; Chen, Y; Williams, C M; Cheng, J J

    2010-05-01

    Environmentally sound treatment of by-products in a value-adding process is an ongoing challenge in animal agriculture. The sludge produced as a result of the dissolved air flotation (DAF) wastewater treatment process in swine processing facilities is one such low-value residue. The objective of this study was to determine the fundamental performance parameters for thermophilic anaerobic digestion of DAF sludge. Testing in a semi-continuous stirred tank reactor and in batch reactors was conducted to determine the kinetics of degradation and biogas yield. Stable operation could not be achieved using pure DAF sludge as a substrate, possibly due to inhibition by long-chain fatty acids or to nutrient deficiencies. However, in a 1:1 ratio (w/w, dry basis) with swine manure, operation was both stable and productive. In the semi-continuous stirred reactor at 54.5 degrees Celsius, a hydraulic residence time of 10 days, and an organic loading rate of 4.68 gVS/day/L, the methane production rate was 2.19 L/L/day and the specific methane production rate was 0.47 L/gVS (fed). Maximum specific methanogenic activity (SMA) in batch testing was 0.15 mmoles CH(4) h(-1) gVS(-1) at a substrate concentration of 6.9 gVS L(-1). Higher substrate concentrations cause an initial lag in methane production, possibly due to long-chain fatty acid or nitrogen inhibition. Copyright 2009 Elsevier Ltd. All rights reserved.

  15. DAFS study of local structure of ordered nanodomains in PbMg1/3Nb2/3O3

    International Nuclear Information System (INIS)

    Frenkel, A.I.; Robinson, I.K.; Robinson, I.K.; Adler, D.L.; Cross, J.O.

    1998-01-01

    We have performed a Diffraction Anomalous Fine Structure (DAFS) study of a single crystal of the relaxor ferroelectric PbMg 1/3 Nb 2/3 O 3 . DAFS measurements were performed at the Nb K edge on a half-order Bragg reflection originating from the 1:1 ordered nanodomains. DAFS data analysis provided us with the local structure around Nb atoms in the ordered nanodomains. The Nb-O distance in the ordered region was determined to be 0.052(10) Angstrom shorter than half the lattice parameter of the bulk crystal, in good agreement with one model of the ferroelectric phase transition broadening [JETP 84, 994 (1997)]. copyright 1998 American Institute of Physics

  16. Caffeic acid phenethylester increases stress resistance and enhances lifespan in Caenorhabditis elegans by modulation of the insulin-like DAF-16 signalling pathway.

    Science.gov (United States)

    Havermann, Susannah; Chovolou, Yvonni; Humpf, Hans-Ulrich; Wätjen, Wim

    2014-01-01

    CAPE is an active constituent of propolis which is widely used in traditional medicine. This hydroxycinnamic acid derivate is a known activator of the redox-active Nrf2 signalling pathway in mammalian cells. We used C. elegans to investigate the effects of this compound on accumulation of reactive oxygen species and the modulation of the pivotal redox-active pathways SKN-1 and DAF-16 (homologues of Nrf2 and FoxO, respectively) in this model organism; these results were compared to the effects in Hct116 human colon carcinoma cells. CAPE exerts a strong antioxidative effect in C. elegans: The increase of reactive oxygen species induced by thermal stress was diminished by about 50%. CAPE caused a nuclear translocation of DAF-16, but not SKN-1. CAPE increased stress resistance of the nematode against thermal stress and finally a prolongation of the median and maximum lifespan by 9 and 17%, respectively. This increase in stress resistance and lifespan was dependent on DAF-16 as shown in experiments using a DAF-16 loss of function mutant strain. Life prolongation was retained under SKN-1 RNAi conditions showing that the effect is SKN-1 independent. The results of CAPE obtained in C. elegans differed from the results obtained in Hct116 colon carcinoma cells: CAPE also caused strong antioxidative effects in the mammalian cells, but no activation of the FoxO4 signalling pathway was detectable. Instead, an activation of the Nrf2 signalling pathway was shown by luciferase assay and western blots. CAPE activates the insulin-like DAF-16, but not the SKN-1 signalling pathway in C. elegans and therefore enhances the stress resistance and lifespan of this organism. Since modulation of the DAF-16 pathway was found to be a pivotal effect of CAPE in C. elegans, this has to be taken into account for the investigation of the molecular mechanisms of the traditional use of propolis.

  17. FOXO/DAF-16 Activation Slows Down Turnover of the Majority of Proteins in C. elegans.

    Science.gov (United States)

    Dhondt, Ineke; Petyuk, Vladislav A; Cai, Huaihan; Vandemeulebroucke, Lieselot; Vierstraete, Andy; Smith, Richard D; Depuydt, Geert; Braeckman, Bart P

    2016-09-13

    Most aging hypotheses assume the accumulation of damage, resulting in gradual physiological decline and, ultimately, death. Avoiding protein damage accumulation by enhanced turnover should slow down the aging process and extend the lifespan. However, lowering translational efficiency extends rather than shortens the lifespan in C. elegans. We studied turnover of individual proteins in the long-lived daf-2 mutant by combining SILeNCe (stable isotope labeling by nitrogen in Caenorhabditiselegans) and mass spectrometry. Intriguingly, the majority of proteins displayed prolonged half-lives in daf-2, whereas others remained unchanged, signifying that longevity is not supported by high protein turnover. This slowdown was most prominent for translation-related and mitochondrial proteins. In contrast, the high turnover of lysosomal hydrolases and very low turnover of cytoskeletal proteins remained largely unchanged. The slowdown of protein dynamics and decreased abundance of the translational machinery may point to the importance of anabolic attenuation in lifespan extension, as suggested by the hyperfunction theory. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  18. FOXO/DAF-16 Activation Slows Down Turnover of the Majority of Proteins in C. elegans

    Directory of Open Access Journals (Sweden)

    Ineke Dhondt

    2016-09-01

    Full Text Available Most aging hypotheses assume the accumulation of damage, resulting in gradual physiological decline and, ultimately, death. Avoiding protein damage accumulation by enhanced turnover should slow down the aging process and extend the lifespan. However, lowering translational efficiency extends rather than shortens the lifespan in C. elegans. We studied turnover of individual proteins in the long-lived daf-2 mutant by combining SILeNCe (stable isotope labeling by nitrogen in Caenorhabditis elegans and mass spectrometry. Intriguingly, the majority of proteins displayed prolonged half-lives in daf-2, whereas others remained unchanged, signifying that longevity is not supported by high protein turnover. This slowdown was most prominent for translation-related and mitochondrial proteins. In contrast, the high turnover of lysosomal hydrolases and very low turnover of cytoskeletal proteins remained largely unchanged. The slowdown of protein dynamics and decreased abundance of the translational machinery may point to the importance of anabolic attenuation in lifespan extension, as suggested by the hyperfunction theory.

  19. Selective expression of a splice variant of decay-accelerating factor in c-erbB-2-positive mammary carcinoma cells showing increased transendothelial invasiveness

    International Nuclear Information System (INIS)

    Brandt, Burkhard; Mikesch, Jan-Hendrik; Simon, Ronald; Roetger, Antje; Kemming, Dirk; Schier, Katrin; Sauter, Guido; Buerger, Horst

    2005-01-01

    By differential-display-PCR a subclone of the SK-BR-3 cell line with high in vitro transendothelial invasiveness was identified to express increased levels of a new alternative splice variant of decay-accelerating factor (DAF). DAF seems to play an important role in some malignant tumours since on the one hand the expression of complement inhibitors on the surface of tumour cells prevents the accumulation of complement factors and in consequence cell lysis. On the other hand, DAF has been identified as a ligand for the CD97 surface receptor which induces cell migration. Immunofluorescence procedures, Western blot analyses, and cDNA clone sequencing were employed to confirm the expression of DAF restricted to invasive tumour cells. Using a radioactive RNA-in situ hybridisation on freshly frozen tissue microarrays and RT-PCR on native tumour tissue, the expression of alternative spliced DAF mRNA was demonstrated in invasive breast cancer. Due to the fact that it could thereby not be detected in normal mammary tissues, it has to be confirmed in larger studies that the DAF splice variant might be a specific tumour marker for invasive breast cancer

  20. Cloning and characterization of cDNAs encoding the complete sequence of decay-accelerating factor of human complement

    International Nuclear Information System (INIS)

    Medof, M.E.; Lublin, D.M.; Holers, V.M.; Ayers, D.J.; Getty, R.R.; Leykam, J.F.; Atkinson, J.P.; Tykocinski, M.L.

    1987-01-01

    cDNAs encoding the complement decay-accelerating factor (DAF) were isolated from HeLa and differentiated HL-60 λgt cDNA libraries by screening with a codon preference oligonucleotide corresponding to DAF NH 2 -terminal amino acids 3-14. The composite cDNA sequence showed a 347-amino acid protein preceded by an NH 2 -terminal leader peptide sequence. The translated sequence beginning at the DAF NH 2 terminus encodes four contiguous ≅ 61-amino acid long repetitive units of internal homology. The repetitive regions contain four conserved cysteines, one proline, one glycine, one glycine/alanine, four leucines/isoleucines/valines, one serine, three tyrosines/phenylalanines, and on tryptophan and show striking homology to similar regions previously identified in factor B, C2, C4 binding protein, factor H, C1r, factor XIII, interleukin 2 receptor, and serum β 2 -glycoprotein I. The consensus repeats are attached to a 70-amino acid long segment rich in serine and threonine (potential O-glycosylation sites), which is in turn followed by a stretch of hydrophobic amino acids. RNA blot analysis of HeLa and HL-60 RNA revealed three DAF mRNA species of 3.1, 2.7, and 2.0 kilobases. The results indicate that portions of the DAF gene may have evolved from a DNA element common to the above proteins, that DAF cDNA predicts a COOH-terminal anchoring polypeptide, and that distinct species of DAF message are elaborated in cells

  1. Evaluation of structure models of Ho2PdSi3 using DAFS, inter alia at a satellite reflection

    International Nuclear Information System (INIS)

    Nentwich, M; Zschornak, M; Richter, C; Meyer, D C

    2014-01-01

    The compounds R 2 PdSi 3 , with R = rare earth, exhibit a very interesting magnetic behavior with two phase transitions. Substituting one in four Si atoms by Pd in HoSi 2 results in a modulation of the aristotype. There are several different variants discussed in literature about the nature of the modulation of this rare-earth compound. Two of the latest models were compared: a 2 × 2 × 1 layer and a 2 × 2 × 8 stack. The chosen method is Diffraction Anomalous Fine Structure (DAFS) and was applied both experimentally and by simulation at different absorption edges and reflections, i. a. a satellite reflection, aiming on finding the correct crystal structure

  2. A new addition to the Phillipsite family of molecular sieves: A divalent metal-ion-framework substituted microporous aluminophosphate (DAF-8)

    Science.gov (United States)

    Barrett, Philip A.; Sankar, Gopinathan; Stephenson, Richard; Catlow, C. Richard A.; Thomas, John Meurig; Jones, Richard H.; Teat, Simon J.

    2006-03-01

    By adding substantial amounts of either Co(II) or Zn(II) salts to a gel composed of Al 2O 3, P 2O 5 and the organic template 1,4-diaminocyclohexane, the tendency to yield layered aluminophosphates (AlPOs) is tilted in favour of the production of three-dimensional microporous MAlPOs: in particular, phase-pure samples of a novel Phillipsite structure (designated Davy-Faraday number 8, DAF-8) are formed.

  3. rBTI reduced β-amyloid-induced toxicity by promoting autophagy-lysosomal degradation via DAF-16 in Caenorhabditis elegans.

    Science.gov (United States)

    Li, Jiao; Cui, Xiaodong; Ma, Xiaoli; Wang, Zhuanhua

    2017-03-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disease, of which β-amyloid (Aβ) induced toxicity was suggested as a main cause. Some substances with prolongevity effects have been shown to be protective against AD. In a previous study we demonstrated that a recombinant buckwheat trypsin inhibitor (rBTI) could prolonge the lifespan in Caenorhabditis elegans (C. elegans). Here, we investigated whether rBTI may benefit to mitigate the AD symptom by feeding the AD model C. elegans CL4176. CL4176 is a transgenic C. elegans expressing human Aβ 3-42 in muscle tissue. The results showed that rBTI not only could extend lifespan but also could reduce Aβ toxicity-triggered body paralysis in AD worms. Further study found the accumulation of Aβ was decreased and autophagy-lysosomal degradation pathway was activated in AD worms treated with rBTI. Moreover, the inhibition of autophagy reduced rBTI-mediated paralysis delay. Genetic analyses showed rBTI increased the transcriptional activity of dauer formation abnormal-16 (DAF-16) and the disruption of daf-16 abolished rBTI-mediated protective effect in AD worms. Taken together, these data indicated that rBTI promoted the autophagy-lysosomal degradation pathway to reduce the Aβ-induced toxicity via DAF-16 in an AD model C. elegans, implying that BTI has the potential to protect against AD. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Co-regulation of the DAF-16 target gene, cyp-35B1/dod-13, by HSF-1 in C. elegans dauer larvae and daf-2 insulin pathway mutants.

    Directory of Open Access Journals (Sweden)

    Wendy B Iser

    2011-03-01

    Full Text Available Insulin/IGF-I-like signaling (IIS has both cell autonomous and non-autonomous functions. In some cases, targets through which IIS regulates cell-autonomous functions, such as cell growth and metabolism, have been identified. In contrast, targets for many non-autonomous IIS functions, such as C. elegans dauer morphogenesis, remain elusive. Here, we report the use of genomic and genetic approaches to identify potential non-autonomous targets of C. elegans IIS. First, we used transcriptional microarrays to identify target genes regulated non-autonomously by IIS in the intestine or in neurons. C. elegans IIS controls expression of a number of stress response genes, which were differentially regulated by tissue-restricted IIS. In particular, expression of sod-3, a MnSOD enzyme, was not regulated by tissue-restricted IIS on the microarrays, while expression of hsp-16 genes was rescued back to wildtype by tissue restricted IIS. One IIS target regulated non-autonomously by age-1 was cyp-35B1/dod-13, encoding a cytochrome P450. Genetic analysis of the cyp-35B1 promoter showed both DAF-16 and HSF-1 are direct regulators. Based on these findings, we propose that hsf-1 may participate in the pathways mediating non-autonomous activities of age-1 in C. elegans.

  5. Co-regulation of the DAF-16 target gene, cyp-35B1/dod-13, by HSF-1 in C. elegans dauer larvae and daf-2 insulin pathway mutants.

    Science.gov (United States)

    Iser, Wendy B; Wilson, Mark A; Wood, William H; Becker, Kevin; Wolkow, Catherine A

    2011-03-09

    Insulin/IGF-I-like signaling (IIS) has both cell autonomous and non-autonomous functions. In some cases, targets through which IIS regulates cell-autonomous functions, such as cell growth and metabolism, have been identified. In contrast, targets for many non-autonomous IIS functions, such as C. elegans dauer morphogenesis, remain elusive. Here, we report the use of genomic and genetic approaches to identify potential non-autonomous targets of C. elegans IIS. First, we used transcriptional microarrays to identify target genes regulated non-autonomously by IIS in the intestine or in neurons. C. elegans IIS controls expression of a number of stress response genes, which were differentially regulated by tissue-restricted IIS. In particular, expression of sod-3, a MnSOD enzyme, was not regulated by tissue-restricted IIS on the microarrays, while expression of hsp-16 genes was rescued back to wildtype by tissue restricted IIS. One IIS target regulated non-autonomously by age-1 was cyp-35B1/dod-13, encoding a cytochrome P450. Genetic analysis of the cyp-35B1 promoter showed both DAF-16 and HSF-1 are direct regulators. Based on these findings, we propose that hsf-1 may participate in the pathways mediating non-autonomous activities of age-1 in C. elegans.

  6. Diapause formation and downregulation of insulin-like signaling via DAF-16/FOXO delays axonal degeneration and neuronal loss.

    Directory of Open Access Journals (Sweden)

    Andrea Calixto

    Full Text Available Axonal degeneration is a key event in the pathogenesis of neurodegenerative conditions. We show here that mec-4d triggered axonal degeneration of Caenorhabditis elegans neurons and mammalian axons share mechanistical similarities, as both are rescued by inhibition of calcium increase, mitochondrial dysfunction, and NMNAT overexpression. We then explore whether reactive oxygen species (ROS participate in axonal degeneration and neuronal demise. C. elegans dauers have enhanced anti-ROS systems, and dauer mec-4d worms are completely protected from axonal degeneration and neuronal loss. Mechanistically, downregulation of the Insulin/IGF-1-like signaling (IIS pathway protects neurons from degenerating in a DAF-16/FOXO-dependent manner and is related to superoxide dismutase and catalase-increased expression. Caloric restriction and systemic antioxidant treatment, which decrease oxidative damage, protect C. elegans axons from mec-4d-mediated degeneration and delay Wallerian degeneration in mice. In summary, we show that the IIS pathway is essential in maintaining neuronal homeostasis under pro-degenerative stimuli and identify ROS as a key intermediate of neuronal degeneration in vivo. Since axonal degeneration represents an early pathological event in neurodegeneration, our work identifies potential targets for therapeutic intervention in several conditions characterized by axonal loss and functional impairment.

  7. Molecular characterisation of Colombian yam germplasm by "DNA amplification fingerprinting (DAF" in radioactivo conditions Caracterización molecular del germoplasma de ñame colombiano utilizando "DNA Amplificaron Fingerprinting (DAF" en condiciones radiactivas

    Directory of Open Access Journals (Sweden)

    Bustamante Silvia L.

    2003-12-01

    Full Text Available Samples from the Universidad de Córdoba's yam collection (Dioscorea spp. and others originating from IITA (International Institute of Tropical Agriculture, Ibadan, Nigeria were molecularly characterised to complement existing information about them. The yam (Diosocorea spp. represents a basic crop for small-scale farmers on the Colombian Atlantic Coast who sow around 20,000 hectares per year. Even though they are dioecious species, only one sex is represented in Colombia; it must also be stated that climatic conditions are not propitious for its flowering. This situation has caused difficulty for work in yam breeding. The yam species and varieties used in the Colombian ABP (Agricultural Biotechnology Programme have been molecularly characterised by AFLPs in a previous publication describing a preliminary study emerging from the need to broaden the characterisation of those accessions kept at the Universidad de Córdoba. Comparisons have also been done with some African accessions donated by IITA. In this article, samples were molecularly characterised by another fingerprinting technique, the DAF technique (DNA Amplification Fingerprinting based on PCR, using random oligonucleotides for generating characteristic band patterns from each individual. The results showed 0.0413 population diversity with 0.9587 average similarity, indicating that the yam collection studied had very little genetic diversity and, probably, this could be why the crop is vulnerable to plagues and diseases, as happened at the end of the 1980s when anthracnose practically devastated the crop on the Colombian Atlantic coast. Similarity was also found between those Colombian and African samples analysed, agreeing with low diversity and less distance between common ancestors. The molecular results suggest the need for using other molecular techniques having a greater power of discrimination and also the need to broaden the genetic diversity in yam crops for providing greater

  8. CD97-decay-accelerating factor interaction is not involved in leukocyte adhesion to endothelial cells

    NARCIS (Netherlands)

    Boulday, Gwénola; Hamann, Jörg; Soulillou, Jean-Paul; Charreau, Béatrice

    2002-01-01

    Background. Effective improvement in xenograft survival is achieved using transplants from transgenic pigs expressing human complement (C) regulatory proteins, including decay-accelerating factor (DAF), CD59, and CD46 on endothelial cells (ECs). The aim of this study was to investigate whether human

  9. Final Design for an International Intercomparison Exercise for Nuclear Accident Dosimetry at the DAF Using Godiva-IV: IER-148 CED-2 Report

    Energy Technology Data Exchange (ETDEWEB)

    Heinrichs, Dave [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Beller, Tim [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Burch, Jennifer [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Cummings, Rick [National Security Technologies, LLC. (NSTec), Mercury, NV (United States) Nevada National Security Site; Duluc, Matthieu [Inst. de Radioprotection et de Sûrete Nucleaire (ISRN), Fontenay-aux-Roses (France); Gadd, Milan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Goda, Joetta [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Hickman, David [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); McAvoy, Doug [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Rathbone, Bruce [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Sullivan, Randy [Savannah River Site (SRS), Aiken, SC (United States); Trompier, Francois [Inst. de Radioprotection et de Sûrete Nucleaire (ISRN), Fontenay-aux-Roses (France); Veinot, Ken [Y-12 National Security Complex, Oak Ridge, TN (United States); Ward, Dann [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Will, Rashelle [National Security Technologies, LLC. (NSTec), Mercury, NV (United States) Nevada National Security Site; Wilson, Chris [Atomic Weapons Establishment (AWE), Berkshire (United Kingdom); Zieziulewicz, Thomas [Knolls Atomic Power Lab. (KAPL), Niskayuna, NY (United States)

    2014-09-30

    This document is the Final Design (CED-2) Report for IER-148, “International Inter-comparison Exercise for Nuclear Accident Dosimetry at the DAF Using Godiva-IV.” The report describes the structure of the exercise consisting of three irradiations; identifies the participating laboratories and their points of contact; provides the details of all dosimetry elements and their placement in proximity to Godiva-IV on support stands or phantoms ; and lists the counting and spectroscopy equipment each laboratory will utilize in the Mercury NAD Lab. The exercise is tentatively scheduled for one week in August 2015.

  10. A conserved neuronal DAF-16/FoxO plays an important role in conveying pheromone signals to elicit repulsion behavior in Caenorhabditis elegans.

    Science.gov (United States)

    Park, Donha; Hahm, Jeong-Hoon; Park, Saeram; Ha, Go; Chang, Gyeong-Eon; Jeong, Haelim; Kim, Heekyeong; Kim, Sunhee; Cheong, Eunji; Paik, Young-Ki

    2017-08-03

    Animals use pheromones as a conspecific chemical language to respond appropriately to environmental changes. The soil nematode Caenorhabditis elegans secretes ascaroside pheromones throughout the lifecycle, which influences entry into dauer phase in early larvae, in addition to sexual attraction and aggregation. In adult hermaphrodites, pheromone sensory signals perceived by worms usually elicit repulsion as an initial behavioral signature. However, the molecular mechanisms underlying neuronal pheromone sensory process from perception to repulsion in adult hermaphrodites remain poorly understood. Here, we show that pheromone signals perceived by GPA-3 is conveyed through glutamatergic neurotransmission in which neuronal DAF-16/FoxO plays an important modulatory role by controlling glutaminase gene expression. We further provide evidence that this modulatory role for DAF-16/FoxO seems to be conserved evolutionarily by electro-physiological study in mouse primary hippocampal neurons that are responsible for glutamatergic neurotransmission. These findings provide the basis for understanding the nematode pheromone signaling, which seems crucial for adaptation of adult hermaphrodites to changes in environmental condition for survival.

  11. DAF-18/PTEN signals through AAK-1/AMPK to inhibit MPK-1/MAPK in feedback control of germline stem cell proliferation.

    Directory of Open Access Journals (Sweden)

    Patrick Narbonne

    2017-04-01

    Full Text Available Under replete growth conditions, abundant nutrient uptake leads to the systemic activation of insulin/IGF-1 signalling (IIS and the promotion of stem cell growth/proliferation. Activated IIS can stimulate the ERK/MAPK pathway, the activation of which also supports optimal stem cell proliferation in various systems. Stem cell proliferation rates can further be locally refined to meet the resident tissue's need for differentiated progeny. We have recently shown that the accumulation of mature oocytes in the C. elegans germ line, through DAF-18/PTEN, inhibits adult germline stem cell (GSC proliferation, despite high systemic IIS activation. We show here that this feedback occurs through a novel cryptic signalling pathway that requires PAR-4/LKB1, AAK-1/AMPK and PAR-5/14-3-3 to inhibit the activity of MPK-1/MAPK, antagonize IIS, and inhibit both GSC proliferation and the production of additional oocytes. Interestingly, our results imply that DAF-18/PTEN, through PAR-4/LKB1, can activate AAK-1/AMPK in the absence of apparent energy stress. As all components are conserved, similar signalling cascades may regulate stem cell activities in other organisms and be widely implicated in cancer.

  12. Neuronal migration is regulated by endogenous RNAi and chromatin-binding factor ZFP-1/AF10 in Caenorhabditis elegans.

    Science.gov (United States)

    Kennedy, Lisa M; Grishok, Alla

    2014-05-01

    Endogenous short RNAs and the conserved plant homeodomain (PHD) zinc-finger protein ZFP-1/AF10 regulate overlapping sets of genes in Caenorhabditis elegans, which suggests that they control common biological pathways. We have shown recently that the RNAi factor RDE-4 and ZFP-1 negatively modulate transcription of the insulin/PI3 signaling-dependent kinase PDK-1 to promote C. elegans fitness. Moreover, we have demonstrated that the insulin/IGF-1-PI3K-signaling pathway regulates the activity of the DAF-16/FOXO transcription factor in the hypodermis to nonautonomously promote the anterior migrations of the hermaphrodite-specific neurons (HSNs) during embryogenesis of C. elegans. In this study, we implicate the PHD-containing isoform of ZFP-1 and endogenous RNAi in the regulation of HSN migration. ZFP-1 affects HSN migration in part through its negative effect on pdk-1 transcription and modulation of downstream DAF-16 activity. We also identify a novel role for ZFP-1 and RNAi pathway components, including RDE-4, in the regulation of HSN migration in parallel with DAF-16. Therefore, the coordinated activities of DAF-16, ZFP-1, and endogenous RNAi contribute to gene regulation during development to ensure proper neuronal positioning.

  13. Design, performance and economics of the DAF Indal 50 kW and 375 kW vertical axis wind turbine

    Science.gov (United States)

    Schienbein, L. A.; Malcolm, D. J.

    1982-03-01

    A review of the development and performance of the DAF Indal 50 kW vertical axis Darrieus wind turbines shows that a high level of technical development and reliability has been achieved. Features of the drive train, braking and control systems are discussed and performance details are presented. A description is given of a wind-diesel hybrid presently being tested. Details are also presented of a 375 kW VAWT planned for production in late 1982. A discussion of the economics of both the 50 kW and 375 kW VAWTs is included, showing the effects of charge rate, installed cost, operating cost, performance and efficiency. The energy outputs are translated into diesel fuel cost savings for remote communities.

  14. Dataset of the human homologues and orthologues of lipid-metabolic genes identified as DAF-16 targets their roles in lipid and energy metabolism

    Directory of Open Access Journals (Sweden)

    Lavender Yuen-Nam Fan

    2017-04-01

    Full Text Available The data presented in this article are related to the review article entitled ‘Unravelling the role of fatty acid metabolism in cancer through the FOXO3-FOXM1 axis’ (Saavedra-Garcia et al., 2017 [24]. Here, we have matched the DAF-16/FOXO3 downstream genes with their respective human orthologues and reviewed the roles of these targeted genes in FA metabolism. The list of genes listed in this article are precisely selected from literature reviews based on their functions in mammalian FA metabolism. The nematode Caenorhabditis elegans gene orthologues of the genes are obtained from WormBase, the online biological database of C. elegans. This dataset has not been uploaded to a public repository yet.

  15. Dataset of the human homologues and orthologues of lipid-metabolic genes identified as DAF-16 targets their roles in lipid and energy metabolism.

    Science.gov (United States)

    Fan, Lavender Yuen-Nam; Saavedra-García, Paula; Lam, Eric Wing-Fai

    2017-04-01

    The data presented in this article are related to the review article entitled 'Unravelling the role of fatty acid metabolism in cancer through the FOXO3-FOXM1 axis' (Saavedra-Garcia et al., 2017) [24]. Here, we have matched the DAF-16/FOXO3 downstream genes with their respective human orthologues and reviewed the roles of these targeted genes in FA metabolism. The list of genes listed in this article are precisely selected from literature reviews based on their functions in mammalian FA metabolism. The nematode Caenorhabditis elegans gene orthologues of the genes are obtained from WormBase, the online biological database of C. elegans. This dataset has not been uploaded to a public repository yet.

  16. Carnitine protects the nematode Caenorhabditis elegans from glucose-induced reduction of survival depending on the nuclear hormone receptor DAF-12

    International Nuclear Information System (INIS)

    Deusing, Dorothé Jenni; Beyrer, Melanie; Fitzenberger, Elena; Wenzel, Uwe

    2015-01-01

    Besides its function in transport of fatty acids into mitochondria in order to provide substrates for β-oxidation, carnitine has been shown to affect also glucose metabolism and to inhibit several mechanisms associated with diabetic complications. In the present study we used the mev-1 mutant of the nematode Caenorhabditis elegans fed on a high glucose concentration in liquid media as a diabetes model and tested the effects of carnitine supplementation on their survival under heat-stress. Carnitine at 100 μM completely prevented the survival reduction that was caused by the application of 10 mM glucose. RNA-interference for sir-2.1, a candidate genes mediating the effects of carnitine revealed no contribution of the sirtuin for the rescue of survival. Under daf-12 RNAi rescue of survival by carnitine was abolished. RNA-interference for γ-butyrobetaine hydroxylase 2, encoding the key enzyme for carnitine biosynthesis did neither increase glucose toxicity nor prevent the rescue of survival by carnitine, suggesting that the effects of carnitine supplementation on carnitine levels were significant. Finally, it was demonstrated that neither the amount of lysosomes nor the proteasomal activity were increased by carnitine, excluding that protein degradation pathways, such as autophagy or proteasomal degradation, are involved in the protective carnitine effects. In conclusion, carnitine supplementation prevents the reduction of survival caused by glucose in C. elegans in dependence on a nuclear hormone receptor which displays high homologies to the vertebrate peroxisomal proliferator activated receptors. - Highlights: • Carnitine protects from glucose-induced reduction of stress-resistance. • Carnitine acts via the PPAR homolog DAF-12 on glucose toxicity. • Carnitine protects from glucose toxicity independent of protein degradation

  17. Carnitine protects the nematode Caenorhabditis elegans from glucose-induced reduction of survival depending on the nuclear hormone receptor DAF-12

    Energy Technology Data Exchange (ETDEWEB)

    Deusing, Dorothé Jenni, E-mail: Dorothe.J.Deusing@ernaehrung.uni-giessen.de; Beyrer, Melanie, E-mail: m.beyrer@web.de; Fitzenberger, Elena, E-mail: Elena.Fitzenberger@ernaehrung.uni-giessen.de; Wenzel, Uwe, E-mail: uwe.wenzel@ernaehrung.uni-giessen.de

    2015-05-08

    Besides its function in transport of fatty acids into mitochondria in order to provide substrates for β-oxidation, carnitine has been shown to affect also glucose metabolism and to inhibit several mechanisms associated with diabetic complications. In the present study we used the mev-1 mutant of the nematode Caenorhabditis elegans fed on a high glucose concentration in liquid media as a diabetes model and tested the effects of carnitine supplementation on their survival under heat-stress. Carnitine at 100 μM completely prevented the survival reduction that was caused by the application of 10 mM glucose. RNA-interference for sir-2.1, a candidate genes mediating the effects of carnitine revealed no contribution of the sirtuin for the rescue of survival. Under daf-12 RNAi rescue of survival by carnitine was abolished. RNA-interference for γ-butyrobetaine hydroxylase 2, encoding the key enzyme for carnitine biosynthesis did neither increase glucose toxicity nor prevent the rescue of survival by carnitine, suggesting that the effects of carnitine supplementation on carnitine levels were significant. Finally, it was demonstrated that neither the amount of lysosomes nor the proteasomal activity were increased by carnitine, excluding that protein degradation pathways, such as autophagy or proteasomal degradation, are involved in the protective carnitine effects. In conclusion, carnitine supplementation prevents the reduction of survival caused by glucose in C. elegans in dependence on a nuclear hormone receptor which displays high homologies to the vertebrate peroxisomal proliferator activated receptors. - Highlights: • Carnitine protects from glucose-induced reduction of stress-resistance. • Carnitine acts via the PPAR homolog DAF-12 on glucose toxicity. • Carnitine protects from glucose toxicity independent of protein degradation.

  18. CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis

    NARCIS (Netherlands)

    Ozen, Ahmet; Comrie, William A; Ardy, Rico C; Domínguez Conde, Cecilia; Dalgic, Buket; Beser, Ömer F; Morawski, Aaron R; Karakoc-Aydiner, Elif; Tutar, Engin; Baris, Safa; Ozcay, Figen; Serwas, Nina K; Zhang, Yu; Matthews, Helen F; Pittaluga, Stefania; Folio, Les R; Unlusoy Aksu, Aysel; McElwee, Joshua J; Krolo, Ana; Kiykim, Ayca; Baris, Zeren; Gulsan, Meltem; Ogulur, Ismail; Snapper, Scott B; Houwen, Roderick H J; Leavis, Helen L; Ertem, Deniz; Kain, Renate; Sari, Sinan; Erkan, Tülay; Su, Helen C; Boztug, Kaan; Lenardo, Michael J

    2017-01-01

    BACKGROUND: Studies of monogenic gastrointestinal diseases have revealed molecular pathways critical to gut homeostasis and enabled the development of targeted therapies. METHODS: We studied 11 patients with abdominal pain and diarrhea caused by early-onset protein-losing enteropathy with primary

  19. The GATA transcription factor egl-27 delays aging by promoting stress resistance in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Xiao Xu

    Full Text Available Stress is a fundamental aspect of aging, as accumulated damage from a lifetime of stress can limit lifespan and protective responses to stress can extend lifespan. In this study, we identify a conserved Caenorhabditis elegans GATA transcription factor, egl-27, that is involved in several stress responses and aging. We found that overexpression of egl-27 extends the lifespan of wild-type animals. Furthermore, egl-27 is required for the pro-longevity effects from impaired insulin/IGF-1 like signaling (IIS, as reduced egl-27 activity fully suppresses the longevity of worms that are mutant for the IIS receptor, daf-2. egl-27 expression is inhibited by daf-2 and activated by pro-longevity factors daf-16/FOXO and elt-3/GATA, suggesting that egl-27 acts at the intersection of IIS and GATA pathways to extend lifespan. Consistent with its role in IIS signaling, we found that egl-27 is involved in stress response pathways. egl-27 expression is induced in the presence of multiple stresses, its targets are significantly enriched for many types of stress genes, and altering levels of egl-27 itself affects survival to heat and oxidative stress. Finally, we found that egl-27 expression increases between young and old animals, suggesting that increased levels of egl-27 in aged animals may act to promote stress resistance. These results identify egl-27 as a novel factor that links stress and aging pathways.

  20. Partial characterization of the cross-reacting determinant, a carbohydrate epitope shared by decay accelerating factor and the variant surface glycoprotein of the African Trypanosoma brucei.

    Science.gov (United States)

    Shak, S; Davitz, M A; Wolinsky, M L; Nussenzweig, V; Turner, M J; Gurnett, A

    1988-03-15

    The variant surface glycoprotein (VSG) of the African trypanosome is anchored in the cell membrane by a complex glycan attached to phosphatidylinositol. The carboxyl terminal portion of VSG contains a cryptic carbohydrate epitope, the cross-reacting determinant (CRD), that is revealed only after removal of the diacylglycerol by phosphatidylinositol-specific phospholipase C (PIPLC) or VSG lipase. Recently, we have shown that after hydrolysis by PIPLC, decay-accelerating factor (DAF)--a mammalian phosphatidylinositol-anchored protein--also contains the CRD epitope. Using a two site immunoradiometric assay in which the capturing antibody is a monoclonal antibody to DAF and the revealing antibody is anti-CRD, we now show that sugar phosphates significantly inhibited the binding of anti-CRD antibody to DAF released by PIPLC. DL-myo-inositol 1,2-cyclic phosphate was the most potent inhibitor of binding (IC50 less than 10(-8) M). Other sugar phosphates, such as alpha-D-glucose-1-phosphate, which also possess adjacent hydroxyl and phosphate moieties in cis also inhibited binding at low concentrations (IC50 = 10(-5) to 10(-4) M). In contrast, sugar phosphates which do not possess adjacent hydroxyl and phosphate moieties in cis and simple sugars weakly inhibited binding (IC50 greater than 10(-3) M). These results suggest that myo-inositol 1,2-cyclic phosphate contributes significantly to the epitope recognized by the anti-CRD antibody and is consistent with analysis of the carboxyl terminus of VSG, which also suggested the presence of the cyclic inositol phosphate. In light of the recent findings that human serum contains a glycan-phosphatidyl-inositol-specific phospholipase D, which converts DAF from a hydrophobic to a hydrophilic form lacking the CRD, the observation that the phosphate is crucial for expression of the epitope may be relevant in understanding the origin of CRD-negative DAF in urine and plasma.

  1. Fine tuning of RFX/DAF-19-regulated target gene expression through binding to multiple sites in Caenorhabditis elegans

    OpenAIRE

    Chu, Jeffery S. C.; Tarailo-Graovac, Maja; Zhang, Di; Wang, Jun; Uyar, Bora; Tu, Domena; Trinh, Joanne; Baillie, David L.; Chen, Nansheng

    2011-01-01

    In humans, mutations of a growing list of regulatory factor X (RFX) target genes have been associated with devastating genetics disease conditions including ciliopathies. However, mechanisms underlying RFX transcription factors (TFs)-mediated gene expression regulation, especially differential gene expression regulation, are largely unknown. In this study, we explore the functional significance of the co-existence of multiple X-box motifs in regulating differential gene expression in Caenorha...

  2. Using weigh-in-motion data to determine bridge dynamic amplification factor

    Directory of Open Access Journals (Sweden)

    Kalin Jan

    2015-01-01

    Full Text Available The dynamic component of bridge traffic loading is commonly taken into account with a Dynamic Amplification Factor (DAF – the ratio between the maximum dynamic and static load effects on a bridge. In the design codes, this factor is generally higher than in reality. While this is fine for new bridges that must account for various risks during their life-time, it imposes unnecessary conservativism into assessment of the existing well defined bridges. Therefore, analysis of existing bridges should apply more realistic DAF values. One way of obtaining them experimentally is by bridge weigh-in-motion (B-WIM measurements, which use an existing instrumented bridge or culvert to weigh all crossing vehicles at highway speeds. The B-WIM system had been equipped with two methods of obtaining an approximation to the static response of the. The first method uses the sum of influence lines. This method relies on accurate axle identification, the failure of which can have a large influence on the DAF value. The other method uses a pre-determined low-pass filter to remove the dynamic component of the measured signal; however an expert is needed to set the filter parameters. A new approach that tries to eliminate these two drawbacks has been developed. In this approach the parameters for the filter are determined automatically by fitting the filtered response to the sum of the influence lines. The measurement of DAF on a typical bridge site agrees with experiments performed in the ARCHES [1] project: dynamic amplification decreases as static loading increases.

  3. A transcription elongation factor that links signals from the reproductive system to lifespan extension in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Arjumand Ghazi

    2009-09-01

    Full Text Available In Caenorhabditis elegans and Drosophila melanogaster, the aging of the soma is influenced by the germline. When germline-stem cells are removed, aging slows and lifespan is increased. The mechanism by which somatic tissues respond to loss of the germline is not well-understood. Surprisingly, we have found that a predicted transcription elongation factor, TCER-1, plays a key role in this process. TCER-1 is required for loss of the germ cells to increase C. elegans' lifespan, and it acts as a regulatory switch in the pathway. When the germ cells are removed, the levels of TCER-1 rise in somatic tissues. This increase is sufficient to trigger key downstream events, as overexpression of tcer-1 extends the lifespan of normal animals that have an intact reproductive system. Our findings suggest that TCER-1 extends lifespan by promoting the expression of a set of genes regulated by the conserved, life-extending transcription factor DAF-16/FOXO. Interestingly, TCER-1 is not required for DAF-16/FOXO to extend lifespan in animals with reduced insulin/IGF-1 signaling. Thus, TCER-1 specifically links the activity of a broadly deployed transcription factor, DAF-16/FOXO, to longevity signals from reproductive tissues.

  4. Royal Jelly-Mediated Prolongevity and Stress Resistance in Caenorhabditis elegans Is Possibly Modulated by the Interplays of DAF-16, SIR-2.1, HCF-1, and 14-3-3 Proteins.

    Science.gov (United States)

    Wang, Xiaoxia; Cook, Lauren F; Grasso, Lindsay M; Cao, Min; Dong, Yuqing

    2015-07-01

    Recent studies suggest that royal jelly (RJ) and its related substances may have antiaging properties. However, the molecular mechanisms underlying the beneficial effects remain elusive. We report that the effects of RJ and enzyme-treated RJ (eRJ) on life span and health span in Caenorhabditis elegans (C elegans) are modulated by the sophisticated interplays of DAF-16, SIR-2.1, HCF-1, and 14-3-3 proteins. Dietary supplementation with RJ or eRJ increased C. elegans life span in a dose-dependent manner. The RJ and eRJ consumption increased the tolerance of C elegans to oxidative stress, ultraviolet irradiation, and heat shock stress. Our genetic analyses showed that RJ/eRJ-mediated life-span extension requires insulin/IGF-1 signaling and the activities of DAF-16, SIR-2.1, HCF-1, and FTT-2, a 14-3-3 protein. Earlier studies reported that DAF-16/FOXO, SIR-2.1/SIRT1, FTT-2, and HCF-1 have extensive interplays in worms and mammals. Our present findings suggest that RJ/eRJ-mediated promotion of longevity and stress resistance in C elegans is dependent on these conserved interplays. From an evolutionary point of view, this study not only provides new insights into the molecular mechanisms of RJ's action on health span promotion in C elegans, but also has imperative implications in using RJ/eRJ as nutraceuticals to delay aging and age-related disorders. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Comparison of the Soil Dynamic Amplification Factor and Soil Amplification by Using Microtremor and MASW Methods Respectively

    Science.gov (United States)

    Tuncel, Aykut; Cevdet Özdag, Özkan; Pamuk, Eren; Akgün, Mustafa

    2017-12-01

    Single Station Microtremor method, which is widely used nowadays, is an effective and easy applicable method. In this study, dynamic amplification factor distributions of the study area were obtained using scenario earthquake parameters with single station microtremor data gathered at 112 points. In addition, a surface wave active method, which is known as MASW (Multichannel Analysis of Surface Waves), was applied at 43 profiles to calculate the soil amplification values. Dynamic amplification factor (DAF), soil amplification, the predominant soil period (PSP), geology and topography data of the study area were analysed together. Dynamic amplification factor and soil amplification values were obtained 2 or higher at about sea level parts of the study area which are generally composed of alluvial units. Additionally, in high altitude regions that are composed of volcanic rocks, relatively lower dynamic amplification factor and soil amplification values were obtained. The minimum amplification value in the study area was 1.15, while the maximum amplification value was 3.05 according to the dynamic amplification results and the soil amplification values were between 1.16 and 3.85 in harmony. It is seen that the obtained DAF values and the soil amplification values calculated from the seismic velocities are very similar to each other numerically and regionally. Because of this, it is concluded that the values of the soil amplification obtained by the MASW method and the calculated DAF values in this study are in harmony with each other. Although the depths of research in these two calculation methods are different from each other, the similarity of the results allows us to arrive at the result of how effective the ground layer is on the amplification. It has a great importance to calculate the amplification values and other dynamic parameters by in situ measurements for a planned plot because geological units can vary even at very short distances in heterogeneously

  6. Development of taxon-specific sequence characterized amplified region (SCAR) markers based on actin sequences and DNA amplification fingerprinting (DAF): a case study in the Phoma exigua species complex.

    Science.gov (United States)

    Aveskamp, Maikel M; Woudenberg, Joyce H C; de Gruyter, Johannes; Turco, Elena; Groenewald, Johannes Z; Crous, Pedro W

    2009-05-01

    Phoma exigua is considered to be an assemblage of at least nine varieties that are mainly distinguished on the basis of host specificity and pathogenicity. However, these varieties are also reported to be weak pathogens and secondary invaders on non-host tissue. In practice, it is difficult to distinguish P. exigua from its close relatives and to correctly identify isolates up to the variety level, because of their low genetic variation and high morphological similarity. Because of quarantine issues and phytosanitary measures, a robust DNA-based tool is required for accurate and rapid identification of the separate taxa in this species complex. The present study therefore aims to develop such a tool based on unique nucleotide sequence identifiers. More than 60 strains of P. exigua and related species were compared in terms of partial actin gene sequences, or analysed using DNA amplification fingerprinting (DAF) with short, arbitrary, mini-hairpin primers. Fragments in the fingerprint unique to a single taxon were identified, purified and sequenced. Alignment of the sequence data and subsequent primer trials led to the identification of taxon-specific sequence characterized amplified regions (SCARs), and to a set of specific oligonucleotide combinations that can be used to identify these organisms in plant quarantine inspections.

  7. Function of RSKS-1-AAK-2-DAF-16 signaling cascade in enhancing toxicity of multi-walled carbon nanotubes can be suppressed by mir-259 activation in Caenorhabditis elegans

    Science.gov (United States)

    Zhuang, Ziheng; Li, Min; Liu, Hui; Luo, Libo; Gu, Weidong; Wu, Qiuli; Wang, Dayong

    2016-08-01

    Caenorhabditis elegans is an important non-mammalian alternative assay model for toxicological study. Previous study has indicated that exposure to multi-walled carbon nanotubes (MWCNTs) dysregulated the transcriptional expression of mir-259. In this study, we examined the molecular basis for mir-259 in regulating MWCNTs toxicity in nematodes. Mutation of mir-259 induced a susceptible property to MWCNTs toxicity, and MWCNTs exposure induced a significant increase in mir-259::GFP in pharyngeal/intestinal valve and reproductive tract, implying that mir-259 might mediate a protection mechanisms for nematodes against MWCNTs toxicity. RSKS-1, a putative ribosomal protein S6 kinase, acted as the target for mir-259 in regulating MWCNTs toxicity, and mutation of rsks-1 suppressed the susceptible property of mir-259 mutant to MWCNTs toxicity. Moreover, mir-259 functioned in pharynx-intestinal valve and RSKS-1 functioned in pharynx to regulate MWCNTs toxicity. Furthermore, RSKS-1 regulated MWCNTs toxicity by suppressing the function of AAK-2-DAF-16 signaling cascade. Our results will strengthen our understanding the microRNAs mediated protection mechanisms for animals against the toxicity from certain nanomaterials.

  8. Heat shock factor-1 intertwines insulin/IGF-1, TGF-β and cGMP signaling to control development and aging

    Directory of Open Access Journals (Sweden)

    Barna János

    2012-11-01

    Full Text Available Abstract Background Temperature affects virtually all cellular processes. A quick increase in temperature challenges the cells to undergo a heat shock response to maintain cellular homeostasis. Heat shock factor-1 (HSF-1 functions as a major player in this response as it activates the transcription of genes coding for molecular chaperones (also called heat shock proteins that maintain structural integrity of proteins. However, the mechanisms by which HSF-1 adjusts fundamental cellular processes such as growth, proliferation, differentiation and aging to the ambient temperature remain largely unknown. Results We demonstrate here that in Caenorhabditis elegans HSF-1 represses the expression of daf-7 encoding a TGF-β (transforming growth factor-beta ligand, to induce young larvae to enter the dauer stage, a developmentally arrested, non-feeding, highly stress-resistant, long-lived larval form triggered by crowding and starvation. Under favorable conditions, HSF-1 is inhibited by crowding pheromone-sensitive guanylate cyclase/cGMP (cyclic guanosine monophosphate and systemic nutrient-sensing insulin/IGF-1 (insulin-like growth factor-1 signaling; loss of HSF-1 activity allows DAF-7 to promote reproductive growth. Thus, HSF-1 interconnects the insulin/IGF-1, TGF-β and cGMP neuroendocrine systems to control development and longevity in response to diverse environmental stimuli. Furthermore, HSF-1 upregulates another TGF-β pathway-interacting gene, daf-9/cytochrome P450, thereby fine-tuning the decision between normal growth and dauer formation. Conclusion Together, these results provide mechanistic insight into how temperature, nutrient availability and population density coordinately influence development, lifespan, behavior and stress response through HSF-1.

  9. Function of the PHA-4/FOXA transcription factor during C. elegans post-embryonic development

    Directory of Open Access Journals (Sweden)

    Chen Di

    2008-02-01

    Full Text Available Abstract Background pha-4 encodes a forkhead box (FOX A transcription factor serving as the C. elegans pharynx organ identity factor during embryogenesis. Using Serial Analysis of Gene Expression (SAGE, comparison of gene expression profiles between growing stages animals and long-lived, developmentally diapaused dauer larvae revealed that pha-4 transcription is increased in the dauer stage. Results Knocking down pha-4 expression by RNAi during post-embryonic development showed that PHA-4 is essential for dauer recovery, gonad and vulva development. daf-16, which encodes a FOXO transcription factor regulated by insulin/IGF-1 signaling, shows overlapping expression patterns and a loss-of-function post-embryonic phenotype similar to that of pha-4 during dauer recovery. pha-4 RNAi and daf-16 mutations have additive effects on dauer recovery, suggesting these two regulators may function in parallel pathways. Gene expression studies using RT-PCR and GFP reporters showed that pha-4 transcription is elevated under starvation, and a conserved forkhead transcription factor binding site in the second intron of pha-4 is important for the neuronal expression. The vulval transcription of lag-2, which encodes a ligand for the LIN-12/Notch lateral signaling pathway, is inhibited by pha-4 RNAi, indicating that LAG-2 functions downstream of PHA-4 in vulva development. Conclusion Analysis of PHA-4 during post-embryonic development revealed previously unsuspected functions for this important transcriptional regulator in dauer recovery, and may help explain the network of transcriptional control integrating organogenesis with the decision between growth and developmental arrest at the dauer entry and exit stages.

  10. Glycosyl-phosphatidylinositol (GPI)-anchored membrane association of the porcine reproductive and respiratory syndrome virus GP4 glycoprotein and its co-localization with CD163 in lipid rafts

    Energy Technology Data Exchange (ETDEWEB)

    Du, Yijun [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan (China); Pattnaik, Asit K. [School of Veterinary Medicine and Biomedical Sciences and the Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583-0900 (United States); Song, Cheng [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Yoo, Dongwan, E-mail: dyoo@illinois.edu [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Li, Gang, E-mail: dyoo@illinois.edu [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Institute of Animal Science and Veterinary Medicine, Chinese Academy of Agricultural Sciences, Beijing (China)

    2012-03-01

    The porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 4 (GP4) resembles a typical type I membrane protein in its structure but lacks a hydrophilic tail at the C-terminus, suggesting that GP4 may be a lipid-anchored membrane protein. Using the human decay-accelerating factor (DAF; CD55), a known glycosyl-phosphatidylinositol (GPI) lipid-anchored protein, chimeric constructs were made to substitute the GPI-anchor domain of DAF with the putative lipid-anchor domain of GP4, and their membrane association and lipase cleavage were determined in cells. The DAF-GP4 fusion protein was transported to the plasma membrane and was cleaved by phosphatidylinositol-specific phospholipase C (PI-PLC), indicating that the C-terminal domain of GP4 functions as a GPI anchor. Mutational studies for residues adjacent to the GPI modification site and characterization of respective mutant viruses generated from infectious cDNA clones show that the ability of GP4 for membrane association corresponded to virus viability and growth characteristics. The residues T158 ({omega} - 2, where {omega} is the GPI moiety at E160), P159 ({omega} - 1), and M162 ({omega} + 2) of GP4 were determined to be important for virus replication, with M162 being of particular importance for virus infectivity. The complete removal of the peptide-anchor domain in GP4 resulted in a complete loss of virus infectivity. The depletion of cholesterol from the plasma membrane of cells reduced the virus production, suggesting a role of lipid rafts in PRRSV infection. Remarkably, GP4 was found to co-localize with CD163 in the lipid rafts on the plasma membrane. Since CD163 has been reported as a cellular receptor for PRRSV and GP4 has been shown to interact with this receptor, our data implicates an important role of lipid rafts during entry of the virus.

  11. Glycosyl-phosphatidylinositol (GPI)-anchored membrane association of the porcine reproductive and respiratory syndrome virus GP4 glycoprotein and its co-localization with CD163 in lipid rafts

    International Nuclear Information System (INIS)

    Du, Yijun; Pattnaik, Asit K.; Song, Cheng; Yoo, Dongwan; Li, Gang

    2012-01-01

    The porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 4 (GP4) resembles a typical type I membrane protein in its structure but lacks a hydrophilic tail at the C-terminus, suggesting that GP4 may be a lipid-anchored membrane protein. Using the human decay-accelerating factor (DAF; CD55), a known glycosyl-phosphatidylinositol (GPI) lipid-anchored protein, chimeric constructs were made to substitute the GPI-anchor domain of DAF with the putative lipid-anchor domain of GP4, and their membrane association and lipase cleavage were determined in cells. The DAF-GP4 fusion protein was transported to the plasma membrane and was cleaved by phosphatidylinositol-specific phospholipase C (PI-PLC), indicating that the C-terminal domain of GP4 functions as a GPI anchor. Mutational studies for residues adjacent to the GPI modification site and characterization of respective mutant viruses generated from infectious cDNA clones show that the ability of GP4 for membrane association corresponded to virus viability and growth characteristics. The residues T158 (ω − 2, where ω is the GPI moiety at E160), P159 (ω − 1), and M162 (ω + 2) of GP4 were determined to be important for virus replication, with M162 being of particular importance for virus infectivity. The complete removal of the peptide–anchor domain in GP4 resulted in a complete loss of virus infectivity. The depletion of cholesterol from the plasma membrane of cells reduced the virus production, suggesting a role of lipid rafts in PRRSV infection. Remarkably, GP4 was found to co-localize with CD163 in the lipid rafts on the plasma membrane. Since CD163 has been reported as a cellular receptor for PRRSV and GP4 has been shown to interact with this receptor, our data implicates an important role of lipid rafts during entry of the virus.

  12. No Major Host Genetic Risk Factor Contributed to A(H1N12009 Influenza Severity.

    Directory of Open Access Journals (Sweden)

    Koldo Garcia-Etxebarria

    Full Text Available While most patients affected by the influenza A(H1N1 pandemic experienced mild symptoms, a small fraction required hospitalization, often without concomitant factors that could explain such a severe course. We hypothesize that host genetic factors could contribute to aggravate the disease. To test this hypothesis, we compared the allele frequencies of 547,296 genome-wide single nucleotide polymorphisms (SNPs between 49 severe and 107 mild confirmed influenza A cases, as well as against a general population sample of 549 individuals. When comparing severe vs. mild influenza A cases, only one SNP was close to the conventional p = 5×10-8. This SNP, rs28454025, sits in an intron of the GSK233 gene, which is involved in a neural development, but seems not to have any connections with immunological or inflammatory functions. Indirectly, a previous association reported with CD55 was replicated. Although sample sizes are low, we show that the statistical power in our design was sufficient to detect highly-penetrant, quasi-Mendelian genetic factors. Hence, and assuming that rs28454025 is likely to be a false positive, no major genetic factor was detected that could explain poor influenza A course.

  13. No Major Host Genetic Risk Factor Contributed to A(H1N1)2009 Influenza Severity.

    Science.gov (United States)

    Garcia-Etxebarria, Koldo; Bracho, María Alma; Galán, Juan Carlos; Pumarola, Tomàs; Castilla, Jesús; Ortiz de Lejarazu, Raúl; Rodríguez-Dominguez, Mario; Quintela, Inés; Bonet, Núria; Garcia-Garcerà, Marc; Domínguez, Angela; González-Candelas, Fernando; Calafell, Francesc

    2015-01-01

    While most patients affected by the influenza A(H1N1) pandemic experienced mild symptoms, a small fraction required hospitalization, often without concomitant factors that could explain such a severe course. We hypothesize that host genetic factors could contribute to aggravate the disease. To test this hypothesis, we compared the allele frequencies of 547,296 genome-wide single nucleotide polymorphisms (SNPs) between 49 severe and 107 mild confirmed influenza A cases, as well as against a general population sample of 549 individuals. When comparing severe vs. mild influenza A cases, only one SNP was close to the conventional p = 5×10-8. This SNP, rs28454025, sits in an intron of the GSK233 gene, which is involved in a neural development, but seems not to have any connections with immunological or inflammatory functions. Indirectly, a previous association reported with CD55 was replicated. Although sample sizes are low, we show that the statistical power in our design was sufficient to detect highly-penetrant, quasi-Mendelian genetic factors. Hence, and assuming that rs28454025 is likely to be a false positive, no major genetic factor was detected that could explain poor influenza A course.

  14. Co-chaperone p23 regulates C. elegans Lifespan in Response to Temperature.

    Directory of Open Access Journals (Sweden)

    Makoto Horikawa

    2015-04-01

    Full Text Available Temperature potently modulates various physiologic processes including organismal motility, growth rate, reproduction, and ageing. In ectotherms, longevity varies inversely with temperature, with animals living shorter at higher temperatures. Thermal effects on lifespan and other processes are ascribed to passive changes in metabolic rate, but recent evidence also suggests a regulated process. Here, we demonstrate that in response to temperature, daf-41/ZC395.10, the C. elegans homolog of p23 co-chaperone/prostaglandin E synthase-3, governs entry into the long-lived dauer diapause and regulates adult lifespan. daf-41 deletion triggers constitutive entry into the dauer diapause at elevated temperature dependent on neurosensory machinery (daf-10/IFT122, insulin/IGF-1 signaling (daf-16/FOXO, and steroidal signaling (daf-12/FXR. Surprisingly, daf-41 mutation alters the longevity response to temperature, living longer than wild-type at 25°C but shorter than wild-type at 15°C. Longevity phenotypes at 25°C work through daf-16/FOXO and heat shock factor hsf-1, while short lived phenotypes converge on daf-16/FOXO and depend on the daf-12/FXR steroid receptor. Correlatively daf-41 affected expression of DAF-16 and HSF-1 target genes at high temperature, and nuclear extracts from daf-41 animals showed increased occupancy of the heat shock response element. Our studies suggest that daf-41/p23 modulates key transcriptional changes in longevity pathways in response to temperature.

  15. 40 CFR 1042.525 - How do I adjust emission levels to account for infrequently regenerating aftertreatment devices?

    Science.gov (United States)

    2010-07-01

    ... the downward adjustment factor (DAF) using the following equation: DAF = EFH−EFA (d) Sample...−0.10 g/kW-hr = 0.04 g/kW-hr. DAF = 0.50 g/kW-hr−0.14 g/kW-hr = 0.36 g/kW-hr. (e) Ramped-modal...

  16. 40 CFR 1033.535 - Adjusting emission levels to account for infrequently regenerating aftertreatment devices.

    Science.gov (United States)

    2010-07-01

    ... the downward adjustment factor (DAF) using the following equation: DAF = EFH−EFA (d) Sample... = 0.14 g/ bhp-hr−0.10 g/ bhp-hr = 0.04 g/ bhp-hr. DAF = 0.50 g/ bhp-hr−0.14 g/ bhp-hr = 0.36 g/ bhp-hr...

  17. Risk Factors

    Science.gov (United States)

    ... cells do not invade nearby tissues or spread. Risk Factors Key Points Factors That are Known to ... chemicals . Factors That are Known to Increase the Risk of Cancer Cigarette Smoking and Tobacco Use Tobacco ...

  18. UPDM - Unified Profile for DoDAF/MODAF

    Science.gov (United States)

    2012-04-01

    Expected target DoDAF 2.03 – MODAF MODEM – DNDAF 1.7 may also be required by the Canadians – UML for  BPMN  profile • Allows the seamless integration of... BPMN  artefacts into a DoDAF  Architecture along with an exchange environment – Others? – Priorities will be based on demand and participation • UPDM 2...19         ,  ,  ,  . • Provides flow‐down, traceability, integration across sectors • BPMN  integration is under development UPDM – Unified Profile

  19. Transformations. I. The Effect of DAF on Sentence Generation

    Science.gov (United States)

    Salter, David

    1976-01-01

    A hypothesis based on the psycholinguistic derivation of sentences was tested. The task required that sentences temporarily stored in memory be transformed and spoken with delayed auditory feedback. Available from Plenum Publishing Corp., 227 W. 17th St., New York, NY 10011. (Author/RM)

  20. Landeskunde und Interkulturelles Lernen im Fach DaF

    OpenAIRE

    Adam-Cevizoğlu, Claudia

    2011-01-01

    The mediation of German cultural studies has become a firm component of the foreign language lessons, because without knowledge about the culture of the target language communication cannot succeed. However, the aim of the study of the German cultural study lessons should not be to provide a comprehensive picture for the purposes of the actual study of the culture and geography, but to choose from the contents with the help of which then an intercultural competence can be developed. The conce...

  1. Bioinformatic detection of E47, E2F1 and SREBP1 transcription factors as potential regulators of genes associated to acquisition of endometrial receptivity

    Directory of Open Access Journals (Sweden)

    Croxatto Horacio B

    2011-01-01

    Full Text Available Abstract Background The endometrium is a dynamic tissue whose changes are driven by the ovarian steroidal hormones. Its main function is to provide an adequate substrate for embryo implantation. Using microarray technology, several reports have provided the gene expression patterns of human endometrial tissue during the window of implantation. However it is required that biological connections be made across these genomic datasets to take full advantage of them. The objective of this work was to perform a research synthesis of available gene expression profiles related to acquisition of endometrial receptivity for embryo implantation, in order to gain insights into its molecular basis and regulation. Methods Gene expression datasets were intersected to determine a consensus endometrial receptivity transcript list (CERTL. For this cluster of genes we determined their functional annotations using available web-based databases. In addition, promoter sequences were analyzed to identify putative transcription factor binding sites using bioinformatics tools and determined over-represented features. Results We found 40 up- and 21 down-regulated transcripts in the CERTL. Those more consistently increased were C4BPA, SPP1, APOD, CD55, CFD, CLDN4, DKK1, ID4, IL15 and MAP3K5 whereas the more consistently decreased were OLFM1, CCNB1, CRABP2, EDN3, FGFR1, MSX1 and MSX2. Functional annotation of CERTL showed it was enriched with transcripts related to the immune response, complement activation and cell cycle regulation. Promoter sequence analysis of genes revealed that DNA binding sites for E47, E2F1 and SREBP1 transcription factors were the most consistently over-represented and in both up- and down-regulated genes during the window of implantation. Conclusions Our research synthesis allowed organizing and mining high throughput data to explore endometrial receptivity and focus future research efforts on specific genes and pathways. The discovery of possible

  2. The Somatic Reproductive Tissues of C. elegans Promote Longevity through Steroid Hormone Signaling

    Science.gov (United States)

    Yamawaki, Tracy M.; Berman, Jennifer R.; Suchanek-Kavipurapu, Monika; McCormick, Mark; Gaglia, Marta Maria; Lee, Seung-Jae; Kenyon, Cynthia

    2010-01-01

    In Caenorhabditis elegans and Drosophila melanogaster, removing the germline precursor cells increases lifespan. In worms, and possibly also in flies, this lifespan extension requires the presence of somatic reproductive tissues. How the somatic gonad signals other tissues to increase lifespan is not known. The lifespan increase triggered by loss of the germ cells is known to require sterol hormone signaling, as reducing the activity of the nuclear hormone receptor DAF-12, or genes required for synthesis of the DAF-12 ligand dafachronic acid, prevents germline loss from extending lifespan. In addition to sterol signaling, the FOXO transcription factor DAF-16 is required to extend lifespan in animals that lack germ cells. DAF-12/NHR is known to assist with the nuclear accumulation of DAF-16/FOXO in these animals, yet we find that loss of DAF-12/NHR has little or no effect on the expression of at least some DAF-16/FOXO target genes. In this study, we show that the DAF-12-sterol signaling pathway has a second function to activate a distinct set of genes and extend lifespan in response to the somatic reproductive tissues. When germline-deficient animals lacking somatic reproductive tissues are given dafachronic acid, their expression of DAF-12/NHR-dependent target genes is restored and their lifespan is increased. Together, our findings indicate that in C. elegans lacking germ cells, the somatic reproductive tissues promote longevity via steroid hormone signaling to DAF-12. PMID:20824162

  3. The somatic reproductive tissues of C. elegans promote longevity through steroid hormone signaling.

    Directory of Open Access Journals (Sweden)

    Tracy M Yamawaki

    2010-08-01

    Full Text Available In Caenorhabditis elegans and Drosophila melanogaster, removing the germline precursor cells increases lifespan. In worms, and possibly also in flies, this lifespan extension requires the presence of somatic reproductive tissues. How the somatic gonad signals other tissues to increase lifespan is not known. The lifespan increase triggered by loss of the germ cells is known to require sterol hormone signaling, as reducing the activity of the nuclear hormone receptor DAF-12, or genes required for synthesis of the DAF-12 ligand dafachronic acid, prevents germline loss from extending lifespan. In addition to sterol signaling, the FOXO transcription factor DAF-16 is required to extend lifespan in animals that lack germ cells. DAF-12/NHR is known to assist with the nuclear accumulation of DAF-16/FOXO in these animals, yet we find that loss of DAF-12/NHR has little or no effect on the expression of at least some DAF-16/FOXO target genes. In this study, we show that the DAF-12-sterol signaling pathway has a second function to activate a distinct set of genes and extend lifespan in response to the somatic reproductive tissues. When germline-deficient animals lacking somatic reproductive tissues are given dafachronic acid, their expression of DAF-12/NHR-dependent target genes is restored and their lifespan is increased. Together, our findings indicate that in C. elegans lacking germ cells, the somatic reproductive tissues promote longevity via steroid hormone signaling to DAF-12.

  4. Factor XII (Hageman factor) deficiency

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000545.htm Factor XII (Hageman factor) deficiency To use the sharing features on this ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  5. The choice of dynamic amplification factors for the ITER generic port plugs during disruptions

    International Nuclear Information System (INIS)

    Vacas, Christian; Rodriguez, Eduardo; Guirao, Julio; Iglesias, Silvia; Udintsev, Victor; Pak, Sunil; Maquet, Philippe; Roces, Jorge; Casal, Natalia

    2015-01-01

    Highlights: • Dynamic amplification factor is largely influenced by the DFWs geometry and for the type of bond between DFW and DSM. • DAF were calculated by analyzing the deformed shape and not just looking at the absolute values of displacements. • Detailed transient time history non-linear analysis of an MDUP II electro magnetic event has been carried out. • Cuasi-constant damping ratio of 3% has been considered using a generalized proportional damping model. - Abstract: The purpose of this paper is present an overview of the methodology followed to calculate the dynamic amplification factors applied to the electromagnetic loads acting in the ITER generic port plugs. The methodology used for combining an EM transient event with another kind of load is based in the treated of this dynamic EM event as a static load. As first stage a transient dynamic analysis was performed, at the most demanded electromagnetic event [2], to determine the dynamic response of the port plugs. In the same way, have been solved all the time steps of the dynamic event as static loads, it means that the inertial effect has been neglected. The response of each time-step at the dynamic solution has been compared with the same time-step solved as a static load. For this purpose some control points were positioned along the structure at the most representative locations. The key of these calculations is the understanding of the deformed modes affecting the port plug in order to obtain a reasonable dynamic amplification factors that permit the characterization of these loads in a realistic way and does not derive in a too conservative approach. Additionally, the fundamental frequencies and vibration modes of the generic port plug, requested for the characterization of the damping effects at the structure, were calculated in a complementary modal analysis performed for this aim.

  6. 40 CFR 1039.525 - How do I adjust emission levels to account for infrequently regenerating aftertreatment devices?

    Science.gov (United States)

    2010-07-01

    ... measured emission rate. Determine the downward adjustment factor (DAF) using the following equation: DAF... g/kW-hr. UAF = 0.14 g/kW-hr − 0.10 g/kW-hr = 0.04 g/kW-hr. DAF = 0.50 g/kW-hr − 0.14 g/kW-hr = 0.36...

  7. Robust factorization

    DEFF Research Database (Denmark)

    Aanæs, Henrik; Fisker, Rune; Åström, Kalle

    2002-01-01

    Factorization algorithms for recovering structure and motion from an image stream have many advantages, but they usually require a set of well-tracked features. Such a set is in generally not available in practical applications. There is thus a need for making factorization algorithms deal effect...

  8. Organizational factors

    International Nuclear Information System (INIS)

    Holy, J.

    1999-12-01

    The following organizational factors are considered with respect to the human factor and operating safety of nuclear power plants: external influences; objectives and strategy; positions and ways of management; allocation of resources; working with human resources; operators' training; coordination of work; knowledge of organization and management; proceduralization of the topic; labour organizing culture; self-improvement system; and communication. (P.A.)

  9. El factoring

    Directory of Open Access Journals (Sweden)

    Alberto Rosenthal

    1988-04-01

    Full Text Available RESUMEN El artículo  presenta, una conceptualización general de lo que es el factoring, el origen del mismo, su evolución y hace una clasificación de los distintos tipos de factoring.

  10. El factoring

    Directory of Open Access Journals (Sweden)

    Alberto Rosenthal

    2015-04-01

    Full Text Available RESUMEN Se presenta la segunda parte del artículo aparecido en  el número 6 de la revista EAN. Su contenido es complementario a lo expuesto en dicho número, en está aparecen las ventajas del factoring, conveniencias, limitaciones así como la forma  de efectuar un factor en Colombia,  su necesidad, incidencia económica, etc.

  11. Quality factors

    International Nuclear Information System (INIS)

    Kerr, G.D.

    1986-01-01

    The quality factor, Q, is a dimensionless modifier used in converting absorbed dose, expressed in rads (or grays), to dose equivalent, expressed in rems (or seiverts). The dose equivalent is used in radiation protection to account for the biological effectiveness of different kinds of radiation. The quality factor is related to both the linear energy transfer (LET) and relative biological effectiveness (RBE). The RBE's obtained from biological experiments depend in a complex way on the observed biological effect, the specific test organism, and the experimental conditions. Judgement is involved, therefore, in the choice of the quality factor. Questions regarding the adequacy of current Q values for neutrons were raised first in a 1980 statement by the National Council on Radiation Protection (NCRP) and later in a 1985 statement by the International Commission on Radiological Protection (ICRP). In 1980, the NCRP alerted the technical community to possible future increases between a factor of three and ten in the Q for neutrons, and in 1985, the ICRP suggested an increase by a factor of two in Q for neutrons. Both the ICRP and NRCP are now recommending essentially the same guidance with regard to Q for neutrons: an increase by a factor of two. The Q for neutrons is based on a large, albeit unfocused, body of experimental data. In spite of the lack of focus, the data supporting a change in the neutron quality factor are substantial. However, the proposed doubling of Q for neutrons is clouded by other issues regarding its application. 33 refs., 4 figs., 6 tabs

  12. Intestinal Insulin Signaling Encodes Two Different Molecular Mechanisms for the Shortened Longevity Induced by Graphene Oxide in Caenorhabditis elegans

    Science.gov (United States)

    Zhao, Yunli; Yang, Ruilong; Rui, Qi; Wang, Dayong

    2016-04-01

    Graphene oxide (GO) has been shown to cause multiple toxicities in various organisms. However, the underlying molecular mechanisms for GO-induced shortened longevity are still unclear. We employed Caenorhabditis elegans to investigate the possible involvement of insulin signaling pathway in the control of GO toxicity and its underlying molecular mechanisms. Mutation of daf-2, age-1, akt-1, or akt-2 gene induced a resistant property of nematodes to GO toxicity, while mutation of daf-16 gene led to a susceptible property of nematodes to GO toxicity, suggesting that GO may dysregulate the functions of DAF-2/IGF-1 receptor, AGE-1, AKT-1 and AKT-2-mediated kinase cascade, and DAF-16/FOXO transcription factor. Genetic interaction analysis suggested the involvement of signaling cascade of DAF-2-AGE-1-AKT-1/2-DAF-16 in the control of GO toxicity on longevity. Moreover, intestinal RNA interference (RNAi) analysis demonstrated that GO reduced longevity by affecting the functions of signaling cascade of DAF-2-AGE-1-AKT-1/2-DAF-16 in the intestine. DAF-16 could also regulate GO toxicity on longevity by functioning upstream of SOD-3, which encodes an antioxidation system that prevents the accumulation of oxidative stress. Therefore, intestinal insulin signaling may encode two different molecular mechanisms responsible for the GO toxicity in inducing the shortened longevity. Our results highlight the key role of insulin signaling pathway in the control of GO toxicity in organisms.

  13. Decay-accelerating factor 1 deficiency exacerbates leptospiral-induced murine chronic nephritis and renal fibrosis.

    Directory of Open Access Journals (Sweden)

    María F Ferrer

    Full Text Available Leptospirosis is a global zoonosis caused by pathogenic Leptospira, which can colonize the proximal renal tubules and persist for long periods in the kidneys of infected hosts. Here, we characterized the infection of C57BL/6J wild-type and Daf1-/- mice, which have an enhanced host response, with a virulent Leptospira interrogans strain at 14 days post-infection, its persistence in the kidney, and its link to kidney fibrosis at 90 days post-infection. We found that Leptospira interrogans can induce acute moderate nephritis in wild-type mice and is able to persist in some animals, inducing fibrosis in the absence of mortality. In contrast, Daf1-/- mice showed acute mortality, with a higher bacterial burden. At the chronic stage, Daf1-/- mice showed greater inflammation and fibrosis than at 14 days post-infection and higher levels at all times than the wild-type counterpart. Compared with uninfected mice, infected wild-type mice showed higher levels of IL-4, IL-10 and IL-13, with similar levels of α-smooth muscle actin, galectin-3, TGF-β1, IL-17, IFN-γ, and lower IL-12 levels at 90 days post-infection. In contrast, fibrosis in Daf1-/- mice was accompanied by high expression of α-smooth muscle actin, galectin-3, IL-10, IL-13, and IFN-γ, similar levels of TGF-β1, IL-12, and IL-17 and lower IL-4 levels. This study demonstrates the link between Leptospira-induced murine chronic nephritis with renal fibrosis and shows a protective role of Daf1.

  14. Risk factors

    International Nuclear Information System (INIS)

    Dennery, M.; Dupont, M.A.

    2007-01-01

    This article deals with the development of risk management in the gas sector business: why a risk factor legal mention must precede any published financial information? Do gas companies have to face new risks? Is there specific risks bound to gas activities? Why companies want to master their risks? Is it mandatory or just a new habit? Do they expect a real benefit in return? These are the risk management questions that are analyzed in this article which is based on the public communication of 15 gas companies randomly selected over the world. The information comes from their annual reports or from documents available on their web sites. The intention of this document is not to be exhaustive or to make statistics but only to shade light on the risk factors of the gas sector. (J.S.)

  15. Organizational factors

    International Nuclear Information System (INIS)

    Wahlstroem, B.; Kettunen, J.

    2005-01-01

    The goal of this lecture is to give an overview of important concepts connected to organisational factors and to provide an understanding of mechanisms by which they can contribute to safe or unsafe behaviour of people. The lecture gives examples of ways to organise work, organisational deficiencies and good practices applied in safety oriented organisations. The lecture also gives an introduction to international work and Finnish national regulation connected to organisation and management. (orig.)

  16. Factor analysis

    CERN Document Server

    Gorsuch, Richard L

    2013-01-01

    Comprehensive and comprehensible, this classic covers the basic and advanced topics essential for using factor analysis as a scientific tool in psychology, education, sociology, and related areas. Emphasizing the usefulness of the techniques, it presents sufficient mathematical background for understanding and sufficient discussion of applications for effective use. This includes not only theory but also the empirical evaluations of the importance of mathematical distinctions for applied scientific analysis.

  17. Human factors

    International Nuclear Information System (INIS)

    Brown, G.J.

    1991-01-01

    Recent reactor accidents have spurred the major review, described here, of the contribution of operator personnel to safety in Scottish Nuclear Power Stations. The review aims to identify factors leading to the Chernobyl accident and take preventative measures to avoid possible recurrence. Scottish Nuclear power stations aim to remove the operator from a position where failure to take correct action could lead to a safety hazard. Instead operators concentrate on routine and breakdown maintenance and measures are taken to minimize the probability of operator error. The review concluded that most safety procedures were satisfactory but safety analysis supported by good design practices may offer a significant reduction in the risk of operator error. (UK)

  18. Heart disease - risk factors

    Science.gov (United States)

    Heart disease - prevention; CVD - risk factors; Cardiovascular disease - risk factors; Coronary artery disease - risk factors; CAD - risk ... a certain health condition. Some risk factors for heart disease you cannot change, but some you can. ...

  19. Reduced Insulin/Insulin-like Growth Factor-1 Signaling and Dietary Restriction Inhibit Translation but Preserve Muscle Mass in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Depuydt, Geert; Xie, Fang; Petyuk, Vladislav A.; Shanmugam, Nilesh; Smolders, Arne; Dhondt, Ineke; Brewer, Heather M.; Camp, David G.; Smith, Richard D.; Braeckman, Bart P.

    2013-09-03

    Reduced signaling through the C. elegans insulin/IGF1 like tyrosine kinase receptor daf2 and dietary restriction via bacterial dilution are two well-characterized lifespan-extending interventions that operate in parallel or through (partially) independent mechanisms. Using accurate mass and time tag LCMS/MS quantitative proteomics we detected that the abundance of a large number of ribosomal subunits is decreased in response to dietary restriction as well as in the daf2(e1370) insulin/IGF1 receptor mutant. In addition, general protein synthesis levels in these long-lived worms are repressed. Surprisingly, ribosomal transcript levels were not correlated to actual protein abundance, suggesting that posttranscriptional regulation determines ribosome content. Proteomics also revealed increased presence of many structural muscle cell components in long-lived worms, which appears to result from prioritized preservation of muscle cell volume in nutrient-poor conditions or low insulin-like signaling. Activation of DAF16, but not diet-restriction, stimulates mRNA expression of muscle-related genes to prevent muscle atrophy. Important daf2 specific proteome changes include overexpression of aerobic metabolism enzymes and a general activation of stress responsive and immune defense systems, while increased abundance of many protein subunits of the proteasome core complex is a DR-specific characteristic.

  20. Electroweak form factors

    International Nuclear Information System (INIS)

    Singh, S.K.

    2002-01-01

    The present status of electroweak nucleon form factors and the N - Δ transition form factors is reviewed. Particularly the determination of dipole mass M A in the axial vector form factor is discussed

  1. Risk Factors for Scleroderma

    Science.gov (United States)

    ... You are here: Home For Patients Risk Factors Risk Factors for Scleroderma The cause of scleroderma is ... what biological factors contribute to scleroderma pathogenesis. Genetic Risk Scleroderma does not tend to run in families ...

  2. Risk Factors and Prevention

    Science.gov (United States)

    ... Resources Risk Factors & Prevention Back to Patient Resources Risk Factors & Prevention Even people who look healthy and ... Blood Pressure , high cholesterol, diabetes, and thyroid disease. Risk Factors For Arrhythmias and Heart Disease The following ...

  3. Factors and factorizations of graphs proof techniques in factor theory

    CERN Document Server

    Akiyama, Jin

    2011-01-01

    This book chronicles the development of graph factors and factorizations. It pursues a comprehensive approach, addressing most of the important results from hundreds of findings over the last century. One of the main themes is the observation that many theorems can be proved using only a few standard proof techniques. This stands in marked contrast to the seemingly countless, complex proof techniques offered by the extant body of papers and books. In addition to covering the history and development of this area, the book offers conjectures and discusses open problems. It also includes numerous explanatory figures that enable readers to progressively and intuitively understand the most important notions and proofs in the area of factors and factorization.

  4. Amplification factor variable amplifier

    NARCIS (Netherlands)

    Akitsugu, Oshita; Nauta, Bram

    2007-01-01

    PROBLEM TO BE SOLVED: To provide an amplification factor variable amplifier capable of achieving temperature compensation of an amplification factor over a wide variable amplification factor range. ; SOLUTION: A Gilbert type amplification factor variable amplifier 11 amplifies an input signal and

  5. Amplification factor variable amplifier

    NARCIS (Netherlands)

    Akitsugu, Oshita; Nauta, Bram

    2010-01-01

    PROBLEM TO BE SOLVED: To provide an amplification factor variable amplifier capable of achieving temperature compensation of an amplification factor over a wide variable amplification factor range. ;SOLUTION: A Gilbert type amplification factor variable amplifier 11 amplifies an input signal and can

  6. Foundations of factor analysis

    CERN Document Server

    Mulaik, Stanley A

    2009-01-01

    Introduction Factor Analysis and Structural Theories Brief History of Factor Analysis as a Linear Model Example of Factor AnalysisMathematical Foundations for Factor Analysis Introduction Scalar AlgebraVectorsMatrix AlgebraDeterminants Treatment of Variables as Vectors Maxima and Minima of FunctionsComposite Variables and Linear Transformations Introduction Composite Variables Unweighted Composite VariablesDifferentially Weighted Composites Matrix EquationsMulti

  7. Blood coagulation factor VIII

    Indian Academy of Sciences (India)

    Factor VIII (FVIII) functions as a co-factor in the blood coagulation cascade for the proteolytic activation of factor X by factor IXa. Deficiency of FVIII causes hemophilia A, the most commonly inherited bleeding disorder. This review highlights current knowledge on selected aspects of FVIII in which both the scientist and the ...

  8. Constructivism, Factoring, and Beliefs.

    Science.gov (United States)

    Rauff, James V.

    1994-01-01

    Discusses errors made by remedial intermediate algebra students in factoring polynomials in light of student definitions of factoring. Found certain beliefs about factoring to logically imply many of the errors made. Suggests that belief-based teaching can be successful in teaching factoring. (16 references) (Author/MKR)

  9. Factors affecting construction performance: exploratory factor analysis

    Science.gov (United States)

    Soewin, E.; Chinda, T.

    2018-04-01

    The present work attempts to develop a multidimensional performance evaluation framework for a construction company by considering all relevant measures of performance. Based on the previous studies, this study hypothesizes nine key factors, with a total of 57 associated items. The hypothesized factors, with their associated items, are then used to develop questionnaire survey to gather data. The exploratory factor analysis (EFA) was applied to the collected data which gave rise 10 factors with 57 items affecting construction performance. The findings further reveal that the items constituting ten key performance factors (KPIs) namely; 1) Time, 2) Cost, 3) Quality, 4) Safety & Health, 5) Internal Stakeholder, 6) External Stakeholder, 7) Client Satisfaction, 8) Financial Performance, 9) Environment, and 10) Information, Technology & Innovation. The analysis helps to develop multi-dimensional performance evaluation framework for an effective measurement of the construction performance. The 10 key performance factors can be broadly categorized into economic aspect, social aspect, environmental aspect, and technology aspects. It is important to understand a multi-dimension performance evaluation framework by including all key factors affecting the construction performance of a company, so that the management level can effectively plan to implement an effective performance development plan to match with the mission and vision of the company.

  10. The joy of factoring

    CERN Document Server

    Wagstaff, Samuel S

    2013-01-01

    This book is about the theory and practice of integer factorization presented in a historic perspective. It describes about twenty algorithms for factoring and a dozen other number theory algorithms that support the factoring algorithms. Most algorithms are described both in words and in pseudocode to satisfy both number theorists and computer scientists. Each of the ten chapters begins with a concise summary of its contents. The book starts with a general explanation of why factoring integers is important. The next two chapters present number theory results that are relevant to factoring. Further on there is a chapter discussing, in particular, mechanical and electronic devices for factoring, as well as factoring using quantum physics and DNA molecules. Another chapter applies factoring to breaking certain cryptographic algorithms. Yet another chapter is devoted to practical vs. theoretical aspects of factoring. The book contains more than 100 examples illustrating various algorithms and theorems. It also co...

  11. Factor VII deficiency

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000548.htm Factor VII deficiency To use the sharing features on this page, please enable JavaScript. Factor VII (seven) deficiency is a disorder caused by a ...

  12. Annual Adjustment Factors

    Data.gov (United States)

    Department of Housing and Urban Development — The Department of Housing and Urban Development establishes the rent adjustment factors - called Annual Adjustment Factors (AAFs) - on the basis of Consumer Price...

  13. Stroke - risk factors

    Science.gov (United States)

    ... oxygen. Brain cells can die, causing lasting damage. Risk factors are things that increase your chance of ... a disease or condition. This article discusses the risk factors for stroke and things you can do ...

  14. Human factors in training

    International Nuclear Information System (INIS)

    Dutton, J.W.; Brown, W.R.

    1981-01-01

    The Human Factors concept is a focused effort directed at those activities which require human involvement. Training is, by its nature, an activity totally dependent on the Human Factor. This paper identifies several concerns significant to training situations and discusses how Human Factor awareness can increase the quality of learning. Psychology in the training arena is applied Human Factors. Training is a method of communication represented by sender, medium, and receiver. Two-thirds of this communications model involves the human element directly

  15. Neutron electromagnetic form factors

    International Nuclear Information System (INIS)

    Finn, J.M.; Madey, R.; Eden, T.; Markowitz, P.; Rutt, P.M.; Beard, K.; Anderson, B.D.; Baldwin, A.R.; Keane, D.; Manley, D.M.; Watson, J.W.; Zhang, W.M.; Kowalski, S.; Bertozzi, W.; Dodson, G.; Farkhondeh, M.; Dow, K.; Korsch, W.; Tieger, D.; Turchinetz, W.; Weinstein, L.; Gross, F.; Mougey, J.; Ulmer, P.; Whitney, R.; Reichelt, T.; Chang, C.C.; Kelly, J.J.; Payerle, T.; Cameron, J.; Ni, B.; Spraker, M.; Barkhuff, D.; Lourie, R.; Verst, S.V.; Hyde-Wright, C.; Jiang, W.-D.; Flanders, B.; Pella, P.; Arenhoevel, H.

    1992-01-01

    Nucleon form factors provide fundamental input for nuclear structure and quark models. Current knowledge of neutron form factors, particularly the electric form factor of the neutron, is insufficient to meet these needs. Developments of high-duty-factor accelerators and polarization-transfer techniques permit new experiments that promise results with small sensitivities to nuclear models. We review the current status of the field, our own work at the MIT/Bates linear accelerator, and future experimental efforts

  16. Disconnected electromagnetic form factors

    International Nuclear Information System (INIS)

    Wilcox, Walter

    2001-01-01

    Preliminary results of a calculation of disconnected nucleon electromagnetic factors factors on the lattice are presented. The implementation of the numerical subtraction scheme is outlined. A comparison of results for electric and magnetic disconnected form factors on two lattice sizes with those of the Kentucky group is presented. Unlike previous results, the results found in this calculation are consistent with zero in these sectors

  17. Mesonic Form Factors

    Energy Technology Data Exchange (ETDEWEB)

    Frederic D. R. Bonnet; Robert G. Edwards; George T. Fleming; Randal Lewis; David Richards

    2003-07-22

    We have started a program to compute the electromagnetic form factors of mesons. We discuss the techniques used to compute the pion form factor and present preliminary results computed with domain wall valence fermions on MILC asqtad lattices, as well as Wilson fermions on quenched lattices. These methods can easily be extended to rho-to-gamma-pi transition form factors.

  18. daf-16/FoxO promotes gluconeogenesis and trehalose synthesis during starvation to support survival

    OpenAIRE

    Hibshman, Jonathan D; Doan, Alexander E; Moore, Brad T; Kaplan, Rebecca EW; Hung, Anthony; Webster, Amy K; Bhatt, Dhaval P; Chitrakar, Rojin; Hirschey, Matthew D; Baugh, L Ryan

    2017-01-01

    eLife digest Most animals rarely have access to a constant supply of food, and so have evolved ways to cope with times of plenty and times of shortage. Insulin is a hormone that travels throughout the body to signal when an animal is well fed. Insulin signaling inhibits the activity of a protein called FoxO, which otherwise switches on and off hundreds of genes to control the starvation response. The roundworm, Caenorhabditis elegans, has been well studied in the laboratory, and often has to ...

  19. Isolation, identification and characterization of organic solvent tolerant protease from Bacillus sp. DAF-01

    Directory of Open Access Journals (Sweden)

    Arastoo Badoei-Dalfard

    2012-01-01

    Full Text Available Introduction: Organic solvent-tolerant bacteria are relatively novel extermophilic microorganisms, which can produce organic tolerant protease with capacity of being used in industrial biotechnology for producing high-value compounds. Therefore, finding of these bacteria has drawn much researchers attention nowadays. Materials and Methods: In this project, samples were collected from a hot spring, located in Jiroft. Samples were incubated in medium supplemented with cyclohexane and toluene for 3 days. Screening of protease producing bacteria was performed on the specific media, SKM (Skim milk agar, based on clear area diameter. The best bacterium was identified based on 16s rDNA gene. Protease activity was considered in different temperatures, pH and organic solvents.Results: Sequence alignment and phylogenetic tree results showed that this bacteria was closely related to Bacillus niacini, with 97% homology. Enzymatic studies showed that, this enzyme was active at a wide range of temperatures, 20-90 °C and it,s optimal activity was in 60 °C. In addition, maximum protease activity was obtained in the 8-9 range of pH, and optimal stability was also at pH 9.0. Protease activity in the presence of methanol, toluene, isopropanol, cyclohexane and DMF ‏showed that, remaining activity was at least 80% compared to the control (without organic solvent Discussion and Conclusion: Thermopilic capacity, being active in alkaline protease and high protease stability in the presence of organic solvents all herald a remarkable application for using in different industries.

  20. International Intercomparison Exercise for Nuclear Accident Dosimetry at the DAF Using GODIVA-IV

    Energy Technology Data Exchange (ETDEWEB)

    Hickman, David [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Hudson, Becka [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-12-15

    The Nuclear Criticality Safety Program operated under the direction of Dr. Jerry McKamy completed the first NNSA Nuclear Accident Dosimetry exercise on May 27, 2016. Participants in the exercise were from Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), Sandia National Laboratory (SNL), Savanah River Site (SRS), Pacific Northwest National Laboratory (PNNL), US Navy, the Atomic Weapons Establishment (United Kingdom) under the auspices of JOWOG 30, and the Institute for Radiological Protection and Nuclear Safety (France) by special invitation and NCSP memorandum of understanding. This exercise was the culmination of a series of Integral Experiment Requests (IER) that included the establishment of the Nuclear Criticality Experimental Research Center, (NCERC) the startup of the Godiva Reactor (IER-194), the establishment of a the Nuclear Accident Dosimetry Laboratory (NAD LAB) in Mercury, NV, and the determination of reference dosimetry values for the mixed neutron and photon radiation field of Godiva within NCERC.

  1. demographic factors associated factors associated with malaria

    African Journals Online (AJOL)

    userpc

    .8%) than those in other nce of 35.4% which was actors can predispose alence of malaria in a study were significantly eveloping guidelines and more effective disease endemic areas (Bashar et therefore attempts to rmation on possible demographic factors d out in four selected geria; Major Ibrahim B. Hospital Zaria, Hajiya.

  2. Aspects of QCD factorization

    International Nuclear Information System (INIS)

    Neubert, Matthias

    2001-01-01

    The QCD factorization approach provides the theoretical basis for a systematic analysis of nonleptonic decay amplitudes of B mesons in the heavy-quark limit. After recalling the basic ideas underlying this formalism, several tests of QCD factorization in the decays B→D (*) L, B→K * γ, and B→πK, ππ are discussed. It is then illustrated how factorization can be used to obtain new constraints on the parameters of the unitarity triangle

  3. Oversimplifying quantum factoring.

    Science.gov (United States)

    Smolin, John A; Smith, Graeme; Vargo, Alexander

    2013-07-11

    Shor's quantum factoring algorithm exponentially outperforms known classical methods. Previous experimental implementations have used simplifications dependent on knowing the factors in advance. However, as we show here, all composite numbers admit simplification of the algorithm to a circuit equivalent to flipping coins. The difficulty of a particular experiment therefore depends on the level of simplification chosen, not the size of the number factored. Valid implementations should not make use of the answer sought.

  4. Radioimmunoassay of human Hageman factor (factor XII)

    International Nuclear Information System (INIS)

    Saito, H.; Ratnoff, O.D.; Pensky, J.

    1976-01-01

    A specific, sensitive, and reproducible radioimmunoassay for human Hageman factor (HF, factor XII) has been developed with purified human HF and monospecific rabbit antibody. Precise measurements of HF antigen were possible for concentrations as low as 0.1 percent of that in normal pooled plasma. A good correlation (correlation coefficient = 0.82) existed between the titers of HF measured by clot-promoting assays and radioimmunoassays among 42 normal adults. Confirming earlier studies, HF antigen was absent in Hageman trait plasma, but other congenital deficient plasmas, including those of individuals with Fletcher trait and Fitzgerald trait, contained normal amounts of HF antigen. HF antigen was reduced in the plasmas of patients with disseminated intravascular coagulation or advanced liver cirrhosis, but it was normal in those of patients with chronic renal failure or patients under treatment with warfarin. HF antigen was detected by this assay in plasmas of primates, but not detectable in plasmas of 11 nonprimate mammalian and one avian species

  5. What Are Rare Clotting Factor Deficiencies?

    Science.gov (United States)

    ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ...

  6. PAYMENT CAPACITY SENSITIVITY FACTORS

    Directory of Open Access Journals (Sweden)

    Daniel BRÎNDESCU – OLARIU

    2014-11-01

    The results of the study facilitate the determination and classification of the main sensitivity factors for the payment capacity at sample level, the establishment of general benchmarks for the payment capacity (as no such benchmarks currently exist in the Romanian literature and the identification of the mechanisms through which the variation of different factors impacts the payment capacity.

  7. Respirator field performance factors

    International Nuclear Information System (INIS)

    Skaggs, B.J.; DeField, J.D.; Strandberg, S.W.; Sutcliffe, C.R.

    1985-01-01

    The Industrial Hygiene Group assisted OSHA and the NRC in measurements of respirator performance under field conditions. They reviewed problems associated with sampling aerosols within the respirator in order to determine fit factors (FFs) or field performance factor (FPF). In addition, they designed an environmental chamber study to determine the effects of temperature and humidity on a respirator wearer

  8. Factors affecting nuclear development

    International Nuclear Information System (INIS)

    Stevens, G.H.; Girouard, P.

    1995-01-01

    Among the factors affecting nuclear development, some depend more or less on public authorities, but many are out of public authorities control (foreign policies, market and deregulation, socials and environmental impacts, public opinion). As far as possible, the following study tries to identify those factors. (D.L.). 2 photos

  9. Soil Forming Factors

    Science.gov (United States)

    It! What is Soil? Chip Off the Old Block Soil Forming Factors Matters of Life and Death Underneath It All Wise Choices A World of Soils Soil Forming Factors 2 A Top to Bottom Guide 3 Making a Soil Monolith 4 Soil Orders 5 State Soil Monoliths 6 Where in the Soil World Are You? >> A Top to

  10. Two-factor authentication

    CERN Document Server

    Stanislav, Mark

    2015-01-01

    During the book, readers will learn about the various technical methods by which two-factor authentication is implemented, security concerns with each type of implementation, and contextual details to frame why and when these technologies should be used. Readers will also be provided with insight about the reasons that two-factor authentication is a critical security control, events in history that have been important to prove why organization and individual would want to use two factor, and core milestones in the progress of growing the market.

  11. Business Intelligence Success Factors

    DEFF Research Database (Denmark)

    Gaardboe, Rikke; Jonasen, Tanja Svarre

    2018-01-01

    Business intelligence (BI) is a strategically important practice in many organizations. Several studies have investigated the factors that contribute to BI success; however, an overview of the critical success factors (CSFs) involved is lacking in the extant literature. We have integrated...... 34 CSFs related to BI success. The distinct CSFs identified in the extant literature relate to project management skills (13 papers), management support (20 papers), and user involvement (11 papers). In the articles with operationalized BI success, we found several distinct factors: system quality...

  12. Human factor reliability program

    International Nuclear Information System (INIS)

    Knoblochova, L.

    2017-01-01

    The human factor's reliability program was at Slovenske elektrarne, a.s. (SE) nuclear power plants. introduced as one of the components Initiatives of Excellent Performance in 2011. The initiative's goal was to increase the reliability of both people and facilities, in response to 3 major areas of improvement - Need for improvement of the results, Troubleshooting support, Supporting the achievement of the company's goals. The human agent's reliability program is in practice included: - Tools to prevent human error; - Managerial observation and coaching; - Human factor analysis; -Quick information about the event with a human agent; -Human reliability timeline and performance indicators; - Basic, periodic and extraordinary training in human factor reliability(authors)

  13. [Human factors in medicine].

    Science.gov (United States)

    Lazarovici, M; Trentzsch, H; Prückner, S

    2017-01-01

    The concept of human factors is commonly used in the context of patient safety and medical errors, all too often ambiguously. In actual fact, the term comprises a wide range of meanings from human-machine interfaces through human performance and limitations up to the point of working process design; however, human factors prevail as a substantial cause of error in complex systems. This article presents the full range of the term human factors from the (emergency) medical perspective. Based on the so-called Swiss cheese model by Reason, we explain the different types of error, what promotes their emergence and on which level of the model error prevention can be initiated.

  14. Shell Buckling Knockdown Factors

    Data.gov (United States)

    National Aeronautics and Space Administration — The Shell Buckling Knockdown Factor (SBKF) Project, NASA Engineering and Safety Center (NESC) Assessment #: 07-010-E, was established in March of 2007 by the NESC in...

  15. Risk factors for neoplasms

    International Nuclear Information System (INIS)

    Brachner, A.; Grosche, B.

    1991-06-01

    A broad survey is given of risk factors for neoplasms. The main carcinogenic substances (including also ionizing radiation and air pollution) are listed, and are correlated with the risk factors for various cancers most frequently explained and discussed in the literature. The study is intended to serve as a basis for a general assessment of the incidence of neoplasms in children, and of cancer mortality in the entire population of Bavaria in the years 1983-1989, or 1979-1988, respectively, with the principal idea of drawing up an environment-related health survey. The study therefore takes into account not only ionizing radiation as a main risk factor, but also other risk factors detectable within the ecologic context, as e.g. industrial installations and their effects, refuse incineration plants or waste dumps, or the social status. (orig./MG) [de

  16. Factor IX assay

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003679.htm Factor IX assay To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  17. Factor VIII assay

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003678.htm Factor VIII assay To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  18. Factor II assay

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003674.htm Factor II assay To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  19. Factor V deficiency

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000550.htm Factor V deficiency To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  20. Rheumatoid factor (RF)

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003548.htm Rheumatoid factor (RF) To use the sharing features on this ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  1. Factor II deficiency

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000549.htm Factor II deficiency To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  2. Factor VII assay

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003676.htm Factor VII assay To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  3. Factor X deficiency

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000553.htm Factor X deficiency To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  4. New microbial growth factor

    Science.gov (United States)

    Bok, S. H.; Casida, L. E., Jr.

    1977-01-01

    A screening procedure was used to isolate from soil a Penicillium sp., two bacterial isolates, and a Streptomyces sp. that produced a previously unknown microbial growth factor. This factor was an absolute growth requirement for three soil bacteria. The Penicillium sp. and one of the bacteria requiring the factor, an Arthrobacter sp., were selected for more extensive study concerning the production and characteristics of the growth factor. It did not seem to be related to the siderochromes. It was not present in soil extract, rumen fluid, or any other medium component tested. It appears to be a glycoprotein of high molecular weight and has high specific activity. When added to the diets for a meadow-vole mammalian test system, it caused an increased consumption of diet without a concurrent increase in rate of weight gain.

  5. Human factors in aviation

    National Research Council Canada - National Science Library

    Salas, Eduardo; Maurino, Daniel E

    2010-01-01

    .... HFA offers a comprehensive overview of the topic, taking readers from the general to the specific, first covering broad issues, then the more specific topics of pilot performance, human factors...

  6. [Risk factors of schizophrenia].

    Science.gov (United States)

    Suvisaari, Jaana

    2010-01-01

    Schizophrenia is a multifactorial, neurodevelopmental disorder caused by a combination of genetic and environmental risk factors. Disturbances of brain development begin prenatally, while different environmental insults further affect postnatal brain maturation during childhood and adolescence. Genome-wide association studies (GWAS) have succeeded in identifying hundreds of new risk variants for common, multifactorial diseases. In schizophrenia research, GWAS have found several rare copy number variants that considerably increase the risk of schizophrenia, and have shown an association between schizophrenia and the major histocompatibility complex. Research on environmental risk factors in recent years has provided new information particularly on risk factors related to pregnancy and childhood rearing environment. Gene-environment interactions have become a central research topic. There is evidence that genetically susceptible children are more vulnerable to the effects of unstable childhood rearing environment and other environmental risk factors.

  7. Human Factors Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — Purpose: The purpose of the Human Factors Laboratory is to further the understanding of highway user needs so that those needs can be incorporated in roadway design,...

  8. Factors Affecting Wound Healing

    Science.gov (United States)

    Guo, S.; DiPietro, L.A.

    2010-01-01

    Wound healing, as a normal biological process in the human body, is achieved through four precisely and highly programmed phases: hemostasis, inflammation, proliferation, and remodeling. For a wound to heal successfully, all four phases must occur in the proper sequence and time frame. Many factors can interfere with one or more phases of this process, thus causing improper or impaired wound healing. This article reviews the recent literature on the most significant factors that affect cutaneous wound healing and the potential cellular and/or molecular mechanisms involved. The factors discussed include oxygenation, infection, age and sex hormones, stress, diabetes, obesity, medications, alcoholism, smoking, and nutrition. A better understanding of the influence of these factors on repair may lead to therapeutics that improve wound healing and resolve impaired wounds. PMID:20139336

  9. The stem factor challenge

    International Nuclear Information System (INIS)

    Russell, M.J.; Steele, R. Jr.; DeWall, K.G.; Watkins, J.C.; Bramwell, D.

    1994-01-01

    One of the most important challenges that still needs to be met in the effort to understand the operation of motor-operated, rising-stem valves is the ability to determine stem factor throughout the valve's load range. The stem factor represents the conversion of operator torque to stem thrust. Determining the stem factor is important because some motor-operated valves (MOVs) cannot be tested in the plant at design basis conditions. The ability of these valves to perform their design basis function (typically, to operate against specified flow and pressure loads) must be ensured by analytical methods or by extrapolating from the results of tests conducted at lower loads. Because the stem factor tends to vary in response to friction and lubrication phenomena that occur during loading and wedging, analytical methods and extrapolation methods have been difficult to develop and implement. Early investigations into variability in the stem factor tended to look only at the tip of the iceberg; they focused on what was happening at torque switch trip, which usually occurs at full wedging. In most stems, the stem factor is better (lower) in the wedging transient than before wedging, so working with torque switch trip data alone led many early researchers to false conclusions about the relationship between stem factor and load. However, research at the Idaho National Engineering Laboratory (INEL) has taken a closer look at what happens during the running portion of the closing stroke along with the wedging portion. This shift in focus is important, because functional failure of a valve typically consists of a failure to isolate flow, not a failure to achieve full wedging. Thus, the stem factor that must be determined for a valve's design basis closing requirements is the one that corresponds with the running load before wedging

  10. Factors Affecting Wound Healing

    OpenAIRE

    Guo, S.; DiPietro, L.A.

    2010-01-01

    Wound healing, as a normal biological process in the human body, is achieved through four precisely and highly programmed phases: hemostasis, inflammation, proliferation, and remodeling. For a wound to heal successfully, all four phases must occur in the proper sequence and time frame. Many factors can interfere with one or more phases of this process, thus causing improper or impaired wound healing. This article reviews the recent literature on the most significant factors that affect cutane...

  11. Los factores de riesgo

    Directory of Open Access Journals (Sweden)

    Justo Senado Dumoy

    1999-01-01

    Full Text Available Sobre el fundamento filosófico de los conceptos de la Dialéctica Materialista, se presenta un análisis en relación con el concepto e interpretación de los Factores de Riesgo.A analysis on the concept and interpretation of risk factors is presented based on the philosophical foundation of the concepts of materialist dialectics.

  12. Brain derived neurotrophic factor

    DEFF Research Database (Denmark)

    Mitchelmore, Cathy; Gede, Lene

    2014-01-01

    Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies are curre......Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies...

  13. Factors Impacting Knowledge Sharing

    DEFF Research Database (Denmark)

    Schulzmann, David; Slepniov, Dmitrij

    The purpose of this paper is to examine various factors affecting knowledge sharing at the R&D center of a Western MNE in China. The paper employs qualitative methodology and is based on the action research and case study research techniques. The findings of the paper advance our understanding...... about factors that affect knowledge sharing. The main emphasis is given to the discussion on how to improve knowledge sharing in global R&D organizations....

  14. FGF growth factor analogs

    Science.gov (United States)

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

    2012-07-24

    The present invention provides a fibroblast growth factor heparin-binding analog of the formula: ##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y and Z are as defined, pharmaceutical compositions, coating compositions and medical devices including the fibroblast growth factor heparin-binding analog of the foregoing formula, and methods and uses thereof.

  15. Factorization and pion form factor in QCD

    International Nuclear Information System (INIS)

    Efremov, A.V.; Radyushkin, A.V.

    1979-01-01

    The behaviour of the pion electromagnetic form factor (EMFF) in the framework of quantum chromodynamics (QCD) is discussed. Pion is considered to be a quark-antiquark bound state. It is proposed to use an OPE description of the bound state structure by matrix elements of certain local gauge-invariant operators. Short-distance quark interactions is proved using a direct analysis of perturbation theory in the α-parametric representation of the Feynman diagrams. It is shown that the short-distance parton picture privides a self-consistent description of the large Q 2 momentum behaviour of the pion EMFF in QCD. Pion EMFF asymptotics is expressed in terms of fu fundamental constants of the theory

  16. [Pathological gambling: risk factors].

    Science.gov (United States)

    Bouju, G; Grall-Bronnec, M; Landreat-Guillou, M; Venisse, J-L

    2011-09-01

    In France, consumption of gambling games increased by 148% between 1960 and 2005. In 2004, gamblers lost approximately 0.9% of household income, compared to 0.4% in 1960. This represents approximately 134 Euros per year and per head. In spite of this important increase, the level remains lower than the European average (1%). However, gambling practices may continue to escalate in France in the next few years, particularly with the recent announce of the legalisation of online games and sports betting. With the spread of legalised gambling, pathological gambling rates may increase in France in the next years, in response to more widely available and more attractive gambling opportunities. In this context, there is a need for better understanding of the risk factors that are implicated in the development and maintenance of pathological gambling. This paper briefly describes the major risk factors for pathological gambling by examining the recent published literature available during the first quarter of 2008. This documentary basis was collected by Inserm for the collective expert report procedure on Gambling (contexts and addictions). Seventy-two articles focusing on risk factors for pathological gambling were considered in this review. Only 47 of them were taken into account for analysis. The selection of these 47 publications was based on the guide on literature analysis established by the French National Agency for Accreditation and Assessment in Health (ANAES, 2000). Some publications from more recent literature have also been added, mostly about Internet gambling. We identify three major types of risk factors implicated in gambling problems: some of them are related to the subject (individual factors), others are related to the object of the addiction, here the gambling activity by itself (structural factors), and the last are related to environment (contextual or situational factors). Thus, the development and maintenance of pathological gambling seems to be

  17. PDP-1 links the TGF-β and IIS pathways to regulate longevity, development, and metabolism.

    Directory of Open Access Journals (Sweden)

    Sri Devi Narasimhan

    2011-04-01

    Full Text Available The insulin/IGF-1 signaling (IIS pathway is a conserved regulator of longevity, development, and metabolism. In Caenorhabditis elegans IIS involves activation of DAF-2 (insulin/IGF-1 receptor tyrosine kinase, AGE-1 (PI 3-kinase, and additional downstream serine/threonine kinases that ultimately phosphorylate and negatively regulate the single FOXO transcription factor homolog DAF-16. Phosphatases help to maintain cellular signaling homeostasis by counterbalancing kinase activity. However, few phosphatases have been identified that negatively regulate the IIS pathway. Here we identify and characterize pdp-1 as a novel negative modulator of the IIS pathway. We show that PDP-1 regulates multiple outputs of IIS such as longevity, fat storage, and dauer diapause. In addition, PDP-1 promotes DAF-16 nuclear localization and transcriptional activity. Interestingly, genetic epistasis analyses place PDP-1 in the DAF-7/TGF-β signaling pathway, at the level of the R-SMAD proteins DAF-14 and DAF-8. Further investigation into how a component of TGF-β signaling affects multiple outputs of IIS/DAF-16, revealed extensive crosstalk between these two well-conserved signaling pathways. We find that PDP-1 modulates the expression of several insulin genes that are likely to feed into the IIS pathway to regulate DAF-16 activity. Importantly, dysregulation of IIS and TGF-β signaling has been implicated in diseases such as Type 2 Diabetes, obesity, and cancer. Our results may provide a new perspective in understanding of the regulation of these pathways under normal conditions and in the context of disease.

  18. Generalised Batho correction factor

    International Nuclear Information System (INIS)

    Siddon, R.L.

    1984-01-01

    There are various approximate algorithms available to calculate the radiation dose in the presence of a heterogeneous medium. The Webb and Fox product over layers formulation of the generalised Batho correction factor requires determination of the number of layers and the layer densities for each ray path. It has been shown that the Webb and Fox expression is inefficient for the heterogeneous medium which is expressed as regions of inhomogeneity rather than layers. The inefficiency of the layer formulation is identified as the repeated problem of determining for each ray path which inhomogeneity region corresponds to a particular layer. It has been shown that the formulation of the Batho correction factor as a product over inhomogeneity regions avoids that topological problem entirely. The formulation in terms of a product over regions simplifies the computer code and reduces the time required to calculate the Batho correction factor for the general heterogeneous medium. (U.K.)

  19. factores psicosociales asociados

    Directory of Open Access Journals (Sweden)

    María Teresa Varela Arévalo

    2007-01-01

    Full Text Available El objetivo de este trabajo fue describir el consumo de sustancias psicoactivas [SPA] ilegales en jóvenes y los factores psicosociales de riesgo y de protección asociados. Participaron 763 estudiantes (46,5% hombres y 52,4% mujeres de una universidad privada de Cali, quienes diligenciaron el cuestionario de factores de riesgo y protección para el consumo de drogas. Los resultados muestran que la marihuana fue la droga de mayor consumo; y que existe una fuerte asociación entre el consumo de las cuatro SPA ilegales (marihuana, opiáceos, cocaína y éxtasis y los factores psicosociales de riesgo y/o protección, principalmente, las habilidades de autocontrol, los preconceptos y valoración de las SPA, la relación con personas consumidoras y los comportamientos perturbadores.

  20. Multi-factor authentication

    Science.gov (United States)

    Hamlet, Jason R; Pierson, Lyndon G

    2014-10-21

    Detection and deterrence of spoofing of user authentication may be achieved by including a cryptographic fingerprint unit within a hardware device for authenticating a user of the hardware device. The cryptographic fingerprint unit includes an internal physically unclonable function ("PUF") circuit disposed in or on the hardware device, which generates a PUF value. Combining logic is coupled to receive the PUF value, combines the PUF value with one or more other authentication factors to generate a multi-factor authentication value. A key generator is coupled to generate a private key and a public key based on the multi-factor authentication value while a decryptor is coupled to receive an authentication challenge posed to the hardware device and encrypted with the public key and coupled to output a response to the authentication challenge decrypted with the private key.

  1. Human factors guides

    International Nuclear Information System (INIS)

    Penington, J.

    1995-10-01

    This document presents human factors guides, which have been developed in order to provide licensees of the AECB with advice as to how to address human factors issues within the design and assessment process. This documents presents the results of a three part study undertaken to develop three guides which are enclosed in this document as Parts B, C and D. As part of the study human factors standards, guidelines, handbooks and other texts were researched, to define those which would be most useful to the users of the guides and for the production of the guides themselves. Detailed specifications were then produced to outline the proposed contents and format of the three guides. (author). 100 refs., 3 tabs., 11 figs

  2. Human factors guides

    Energy Technology Data Exchange (ETDEWEB)

    Penington, J [PHF Services Inc., (Canada)

    1995-10-01

    This document presents human factors guides, which have been developed in order to provide licensees of the AECB with advice as to how to address human factors issues within the design and assessment process. This documents presents the results of a three part study undertaken to develop three guides which are enclosed in this document as Parts B, C and D. As part of the study human factors standards, guidelines, handbooks and other texts were researched, to define those which would be most useful to the users of the guides and for the production of the guides themselves. Detailed specifications were then produced to outline the proposed contents and format of the three guides. (author). 100 refs., 3 tabs., 11 figs.

  3. The focus factor

    DEFF Research Database (Denmark)

    Nicolaisen, Jeppe; Frandsen, Tove Faber

    2015-01-01

    Introduction. We present a new bibliometric indicator to measure journal specialisation over time, named the focus factor. This new indicator is based on bibliographic coupling and counts the percentage of re-citations given in subsequent years. Method. The applicability of the new indicator....... To validate re-citations as caused by specialisation, other possible causes were measured and correlated (obsolescence, journal self-citations and number of references). Results. The results indicate that the focus factor is capable of distinguishing between general and specialised journals and thus...... effectively measures the intended phenomenon (i.e., journal specialisation). Only weak correlations were found between journal re-citations and obsolescence, journal self-citations, and number of references. Conclusions. The focus factor successfully measures journal specialisation over time. Measures based...

  4. WRKY transcription factors

    Science.gov (United States)

    Bakshi, Madhunita; Oelmüller, Ralf

    2014-01-01

    WRKY transcription factors are one of the largest families of transcriptional regulators found exclusively in plants. They have diverse biological functions in plant disease resistance, abiotic stress responses, nutrient deprivation, senescence, seed and trichome development, embryogenesis, as well as additional developmental and hormone-controlled processes. WRKYs can act as transcriptional activators or repressors, in various homo- and heterodimer combinations. Here we review recent progress on the function of WRKY transcription factors in Arabidopsis and other plant species such as rice, potato, and parsley, with a special focus on abiotic, developmental, and hormone-regulated processes. PMID:24492469

  5. On braid monodromy factorizations

    International Nuclear Information System (INIS)

    Kharlamov, V M; Kulikov, Vik S

    2003-01-01

    We introduce and develop a language of semigroups over the braid groups to study the braid monodromy factorizations (bmf's) of plane algebraic curves and other related objects. As an application, we give a new proof of Orevkov's theorem on the realization of bmf's over a disc by algebraic curves and show that the complexity of such a realization cannot be bounded in terms of the types of factors of the bmf. We also prove that the type of a bmf distinguishes Hurwitz curves with singularities of inseparable type up to H-isotopy and J-holomorphic cuspidal curves in CP 2 up to symplectic isotopy

  6. Dose conversion factors

    International Nuclear Information System (INIS)

    Kocher, D.C.; Eckerman, K.F.

    1992-01-01

    The following is discussed in this report: concepts and quantities used in calculating radiation dose from internal and external exposure. Tabulations of dose conversion factor for internal and external exposure to radionuclides. Dose conversion factors give dose per unit intake (internal) or dose per unit concentration in environment (external). Intakes of radionuclides for internal exposure and concentrations of radionuclides in environment for external exposure are assumed to be known. Intakes and concentrations are obtained, e.g., from analyses of environmental transport and exposure pathways. differences between dosimetry methods for radionuclides and hazardous chemicals are highlighted

  7. Factors stimulating content marketing

    Directory of Open Access Journals (Sweden)

    Naser Azad

    2016-02-01

    Full Text Available This paper presents an empirical investigation to determine factors influencing on content marketing in banking industry. The study designs a questionnaire consists of 40 questions in Likert scale and distributes it among 550 randomly selected regular customers of Bank Mellat in city of Tehran, Iran and 400 properly filled questionnaires are collected. Cronbach alphas for all components of the survey are well above desirable level. Using principle component analysis with Varimax rotation, the study has determined six factors influencing the most on content marketing including organization, details, having new ideas, quality, sensitivity and power while the last component contains only two subcomponents and is removed from the study.

  8. STEREOTYPICAL FACTORS IN TOURISM

    Directory of Open Access Journals (Sweden)

    Cristina-Elena ALBU

    2013-06-01

    Full Text Available International tourism has grown rapidly nowdays, contributing to the growth of the global economy. The purpose of this essay is to identify and analyze stereotypical factors in the development of strategies concerning the offer for the tourism industry: the image of a tourist destination, brand, country of origin and customer behaviour. Documentary study was the research method used: representative articles were analysed, as recent as possible, to determine the factors mentioned above. Professionals in the industry of tourism need to understand cultural differences between tourists, as well as those of the host country, to be able to create tourist reception offers that live up to the standards expected by clients.

  9. Factor analysis and scintigraphy

    International Nuclear Information System (INIS)

    Di Paola, R.; Penel, C.; Bazin, J.P.; Berche, C.

    1976-01-01

    The goal of factor analysis is usually to achieve reduction of a large set of data, extracting essential features without previous hypothesis. Due to the development of computerized systems, the use of largest sampling, the possibility of sequential data acquisition and the increase of dynamic studies, the problem of data compression can be encountered now in routine. Thus, results obtained for compression of scintigraphic images were first presented. Then possibilities given by factor analysis for scan processing were discussed. At last, use of this analysis for multidimensional studies and specially dynamic studies were considered for compression and processing [fr

  10. The Transcription Factor Encyclopedia

    DEFF Research Database (Denmark)

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I

    2012-01-01

    mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written......ABSTRACT: Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130...

  11. Factorizations and physical representations

    International Nuclear Information System (INIS)

    Revzen, M; Khanna, F C; Mann, A; Zak, J

    2006-01-01

    A Hilbert space in M dimensions is shown explicitly to accommodate representations that reflect the decomposition of M into prime numbers. Representations that exhibit the factorization of M into two relatively prime numbers: the kq representation (Zak J 1970 Phys. Today 23 51), and related representations termed q 1 q 2 representations (together with their conjugates) are analysed, as well as a representation that exhibits the complete factorization of M. In this latter representation each quantum number varies in a subspace that is associated with one of the prime numbers that make up M

  12. Model Correction Factor Method

    DEFF Research Database (Denmark)

    Christensen, Claus; Randrup-Thomsen, Søren; Morsing Johannesen, Johannes

    1997-01-01

    The model correction factor method is proposed as an alternative to traditional polynomial based response surface techniques in structural reliability considering a computationally time consuming limit state procedure as a 'black box'. The class of polynomial functions is replaced by a limit...... of the model correction factor method, is that in simpler form not using gradient information on the original limit state function or only using this information once, a drastic reduction of the number of limit state evaluation is obtained together with good approximations on the reliability. Methods...

  13. [Natural factors influencing sleep].

    Science.gov (United States)

    Jurkowski, Marek K; Bobek-Billewicz, Barbara

    2007-01-01

    Sleep is a universal phenomenon of human and animal lives, although the importance of sleep for homeo-stasis is still unknown. Sleep disturbances influence many behavioral and physiologic processes, leading to health complications including death. On the other hand, sleep improvement can beneficially influence the course of healing of many disorders and can be a prognostic of health recovery. The factors influencing sleep have different biological and chemical origins. They are classical hormones, hypothalamic releasing and inhibitory hormones, neuropeptides, peptides and others as cytokines, prostaglandins, oleamid, adenosine, nitric oxide. These factors regulate most physiologic processes and are likely elements integrating sleep with physiology and physiology with sleep in health and disorders.

  14. Environmental factors and leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Brandt, L

    1985-01-01

    Investigations on the association between environmental hazards and the development of various types of leukaemia are reviewed. Regarding acute non-lymphocytic leukaemia (ANLL) exposure to ionizing radiation is a well-documented risk factor. According to several recent studies exposure to strong electromagnetic fields may be suspected to be of etiologic importance for ANLL. There is evidence that occupational handling of benzene is a risk factor and other organic solvents may also be leukaemogenic. Occupational exposure to petrol products has been proposed to be a risk factor although the hazardous substances have not yet been defined. Results of cytogenetic studies in ANLL suggest that exposure to certain environmental agents may be associated with relatively specific clonal chromosome aberrations. Exposure in utero to ionizing radiation has been proposed to be a risk factor for acute lymphocytic leukaemia (ALL) in children. Unlike ANLL there seems at present to be little evidence that ALL is related to exposure to some chemicals. Chronic myeloid leukaemia (CML) may follow exposure to high doses of ionizing radiation whereas such exposure seems to be of insignificant importance for the development of chronic lymphocytic leukaemia (CLL). According to some studies an abnormally high incidence of CLL may be found among farmers in the USA. These results have not been confirmed in Scandinavian studies. There seems to be little evidence that CML or CLL are related to occupational handling of some chemicals. 35 references.

  15. Hyperglycemia: a prothrombotic factor?

    NARCIS (Netherlands)

    Lemkes, B. A.; Hermanides, J.; DeVries, J. H.; Holleman, F.; Meijers, J. C. M.; Hoekstra, J. B. L.

    2010-01-01

    Diabetes mellitus is characterized by a high risk of atherothrombotic events. What is more, venous thrombosis has also been found to occur more frequently in this patient group. This prothrombotic condition in diabetes is underpinned by laboratory findings of elevated coagulation factors and

  16. Thermal disadvantage factor

    International Nuclear Information System (INIS)

    Abdullah, K.M.S.; Loyalka, S.K.

    1990-01-01

    A method is described where reactor cell flux and the disadvantage factor are calculated by using diffusion theory in the moderator and integral transport in the fuel. The method is efficient (noniterative) and provides results that agree well with Monte Carlo, P 5 and ABH results

  17. Threshold factorization redux

    Science.gov (United States)

    Chay, Junegone; Kim, Chul

    2018-05-01

    We reanalyze the factorization theorems for the Drell-Yan process and for deep inelastic scattering near threshold, as constructed in the framework of the soft-collinear effective theory (SCET), from a new, consistent perspective. In order to formulate the factorization near threshold in SCET, we should include an additional degree of freedom with small energy, collinear to the beam direction. The corresponding collinear-soft mode is included to describe the parton distribution function (PDF) near threshold. The soft function is modified by subtracting the contribution of the collinear-soft modes in order to avoid double counting on the overlap region. As a result, the proper soft function becomes infrared finite, and all the factorized parts are free of rapidity divergence. Furthermore, the separation of the relevant scales in each factorized part becomes manifest. We apply the same idea to the dihadron production in e+e- annihilation near threshold, and show that the resultant soft function is also free of infrared and rapidity divergences.

  18. Fibroblast growth factor 23

    African Journals Online (AJOL)

    Dr Olaleye

    Systemic phosphate homeostasis is maintained through several hormonal mechanisms which involve fibroblast growth factor 23 (FGF-23), α-klotho, vitamin D and parathyroid hormone. FGF-23 is known to be the major regulator of phosphate balance (Mirams et al., 2004). FGF-23 is a phosphaturic hormone, which is.

  19. Human factors information system

    International Nuclear Information System (INIS)

    Goodman, P.C.; DiPalo, C.A.

    1991-01-01

    Nuclear power plant safety is dependent upon human performance related to plant operations. To provide improvements in human performance, data collection and assessment play key roles. This paper reports on the Human factors Information System (HFIS) which is designed to meet the needs of the human factors specialists of the United States Nuclear Regulatory Commission. These specialists identify personnel errors and provide guidance designed to prevent such errors. HFIS is a simple and modular system designed for use on a personal computer. It is designed to contain four separate modules that provide information indicative of program or function effectiveness as well as safety-related human performance based on programmatic and performance data. These modules include the Human Factors Status module; the Regulatory Programs module; the Licensee Event Report module; and the Operator Requalification Performance module. Information form these modules can either be used separately or can be combined due to the integrated nature of the system. HFIS has the capability, therefore, to provide insights into those areas of human factors that can reduce the probability of events caused by personnel error at nuclear power plants and promote the health and safety of the public. This information system concept can be applied to other industries as well as the nuclear industry

  20. PATTERNS AND FACTORS INVOLVED

    African Journals Online (AJOL)

    Between 1*' of July 1996 and 30'h of June 2000 a total of 3583 patients were registered at the accident and emergency unit of Nnamdi. Azikiwe ... The case files of these were reviewed with a view to ascertaining the causes and factors involved in the deaths of these patients. The .... H.I.V/AIDS related complications 23 6.8.

  1. Introduction to human factors

    International Nuclear Information System (INIS)

    Winters, J.M.

    1988-03-01

    Some background is given on the field of human factors. The nature of problems with current human/computer interfaces is discussed, some costs are identified, ideal attributes of graceful system interfaces are outlined, and some reasons are indicated why it's not easy to fix the problems

  2. Prognostic factors in oligodendrogliomas

    DEFF Research Database (Denmark)

    Westergaard, L; Gjerris, F; Klinken, L

    1997-01-01

    An outcome analysis was performed on 96 patients with pure cerebral oligodendrogliomas operated in the 30-year period 1962 to 1991. The most important predictive prognostic factors were youth and no neurological deficit, demonstrated as a median survival for the group younger than 20 years of 17...

  3. Factors affecting mining costs

    International Nuclear Information System (INIS)

    Lowell, A.F.

    1977-01-01

    The subject is discussed under the following headings: investment decision-making, unit cost factors (declining ore grade, low-price contracts, ore grade/output relationship, above average cost increases). Economic, environmental, sociological and political aspects are considered. (U.K.)

  4. Human factors in network security

    OpenAIRE

    Jones, Francis B.

    1991-01-01

    Human factors, such as ethics and education, are important factors in network information security. This thesis determines which human factors have significant influence on network security. Those factors are examined in relation to current security devices and procedures. Methods are introduced to evaluate security effectiveness by incorporating the appropriate human factors into network security controls

  5. Electromagnetic form factors

    International Nuclear Information System (INIS)

    Desplanques, B.

    1987-01-01

    Electromagnetic form factors, in first approximation, are sensitive to spatial distribution of nucleons and to their current. In second approximation, more precise effects are concerned, whose role is increasing with momentum transfer and participating essentially of short range nuclei description. They concern of course the nucleon-nucleon interaction while approaching each other and keeping their free-state identity, but also mutually polarizing one the other. In this last effect, radial and orbital excitations of nucleon, the nucleon mesonic cloud modification and the nucleon antinucleon pair excitation are included. In this paper, these contributions are discussed while trying to find the important elements for a good description of form factors. Current questions are also discussed. Light nuclei are essentially concerned [fr

  6. Researching organizational factors

    International Nuclear Information System (INIS)

    Coffman, F.

    1991-01-01

    This paper discusses feedback and insights from experience (both successful and unsuccessful) with the past and the ongoing organizational factors research. That experience suggests a leading set of ingredients that appear proper for performing regulatory research on organizational processes. By keeping focused upon these proper ingredients, the research will contribute to the regulatory assessments of utility management through the use of improved methods and measures in investigations, inspections, diagnostics, performance indicators, and PRA insights. This paper is organized into (1) an introductory description of what the agency is doing to assess organizational effectiveness, (2) some insights from past and ongoing research, (3) an opinion on a leading set of ingredients to properly research organizational factors, and (4) a summary

  7. On braid monodromy factorizations

    Energy Technology Data Exchange (ETDEWEB)

    Kharlamov, V M [Institut de Recherche Matematique Avanee Universite Louis Pasteur et CNRS 7 rue Rene Descartes (France); Kulikov, Vik S [Steklov Mathematical Institute, Russian Academy of Sciences (Russian Federation)

    2003-06-30

    We introduce and develop a language of semigroups over the braid groups to study the braid monodromy factorizations (bmf's) of plane algebraic curves and other related objects. As an application, we give a new proof of Orevkov's theorem on the realization of bmf's over a disc by algebraic curves and show that the complexity of such a realization cannot be bounded in terms of the types of factors of the bmf. We also prove that the type of a bmf distinguishes Hurwitz curves with singularities of inseparable type up to H-isotopy and J-holomorphic cuspidal curves in CP{sup 2} up to symplectic isotopy.

  8. Factors in Agile Methods Adoption

    Directory of Open Access Journals (Sweden)

    Samia Abdalhamid

    2017-05-01

    Full Text Available There are many factors that can affect the process of adopting Agile methods during software developing. This paper illustrates the critical factors in Agile methods adoption in software organizations. To present the success and failure factors, an exploratory study is carried out among the critical factors of success and failure from existing studies. Dimensions and Factors are introduced utilizing success and failure dimensions. The mind map was used to clarify these factors.

  9. Factors of academic procrastination

    OpenAIRE

    Kranjec, Eva; Košir, Katja; Komidar, Luka

    2017-01-01

    This study investigated dimensions of perfectionism, anxiety, and depression as factors of academic procrastination. Our main research interest was to examine the role of specific dimensions of perfectionism as moderators in the relationship between anxiety and depression and academic procrastination. Four scales were administered on the sample of 403 students: perfectionism scale FMPS, academic procrastination scale APS-SI, depression scale CESD and anxiety scale STAI-X2. The results showed ...

  10. Concentration factors for fish

    International Nuclear Information System (INIS)

    Feldt, W.; Lauer, R.; Melzer, M.; Siebert, W.

    1978-01-01

    Concentration factors are defined as operators allowing to calculate the specific activity of fish meat from a given concentration of an element in the water. This parameter depends among others from the content of stable isotopes and homologues in the different waters. If this parameter is reasonably to be used for model calculations it must be referred to water with all of its content substances, these calculations also being based on this type of 'water'. (orig.) [de

  11. Prognostic factors for medulloblastoma

    International Nuclear Information System (INIS)

    Jenkin, Derek; Al Shabanah, Mohamed; Al Shail, Essam; Gray, Alan; Hassounah, Maher; Khafaga, Yasser; Kofide, Amani; Mustafa, Mahmoud; Schultz, Henrik

    2000-01-01

    Purpose: To evaluate prognostic factors for medulloblastoma. Methods and Materials: One hundred and seventy-three consecutive patients with medulloblastoma, treated at King Faisal Specialist Hospital (KFSH) from 1988-1997, were reviewed. Eighty-four percent were children less than 15 years old. From 1988-1994, treatment was at the discretion of the investigator. From 1994-1998, patients entered a single-arm best practice protocol in which, in staged patients, the surgical intent was total resection, standard radiation treatment was defined, and adjuvant chemotherapy was given to a 'high-risk' subset. Results: For 150 patients who completed surgical and radiation treatment, the 5-year survival rate was 58%, compared with 0% for 16 patients who were unable to start or complete radiation treatment. For staged patients, the 5-year survival was M0 + M1, 78% and M2 + M3, 21% (p 14 years and gross cystic/necrotic features in the primary tumor. The size of the primary tumor, the degree of hydrocephalus at diagnosis, the presence of residual tumor in the post-operative CT/MRI, and the functional status of the patient prior to radiation treatment were not significant factors. Conclusions: Stage M0 + M1 was the most powerful favorable prognostic factor. In Saudi Arabia more patients present with advanced disseminated disease, 41% M2 + M3, than in the West, and this impacts adversely on overall survival. Total resection and standard radiation treatment were not sensitive prognostic factors in a treatment environment in which 78% of patients underwent at least 90% tumor resection and 60% received standard radiation treatment. In order to improve the proportion of patients able to complete radiation treatment, consideration should be given to limiting resection when the attainment of total resection is likely to be morbid, and to delaying rather than omitting radiation treatment in the patient severely compromised postoperatively

  12. Risk factors for cancer

    International Nuclear Information System (INIS)

    Lyman, G.H.

    1992-01-01

    It is no longer reasonable to divide cancers into those that are genetic in origin and those that are environmental in origin. With rare exception, carcinogenesis involves environmental factors that directly or indirectly exert a change in the cell's genome. Virtually all causes of cancer are multifactorial, sometimes involving an inherited predisposition to the carcinogenic effects of environmental factors, which include chemicals, ionizing radiation, and oncogenic virus. Carcinogenesis is a multistep process including induction, promotion, and progression. Initiation requires an irreversible change in the cellular genome, whereas promotion is commonly associated with prolonged and reversible exposure. Tumor progression results in genotypic and phenotypic changes associated with tumor growth, invasion, and metastasis. Most information on human cancer risk is based on epidemiologic studies involving both exposed and unexposed individuals. The quality of such studies depends on their ability to assess the strength of any association of exposure and disease and careful attention to any potential bias. Few cancers are inherited in a Mendelian fashion. Several preneoplastic conditions, however, are clearly inherited and several malignancies demonstrate weak familial patterns. Environmental factors may exert their effect on DNA in a random fashion, but certain consistent changes, including specific translocations of genetic information, are often found. Currently, there is great interest in the close proximity of certain oncogenes governing growth control to the consistent chromosomal changes observed. Such changes may represent a final common pathway of action for environmental carcinogens. Sufficient laboratory and epidemiologic evidence exists to establish a causal association of several chemical agents with cancer

  13. Human factoring administrative procedures

    International Nuclear Information System (INIS)

    Grider, D.A.; Sturdivant, M.H.

    1991-01-01

    In nonnuclear business, administrative procedures bring to mind such mundane topics as filing correspondence and scheduling vacation time. In the nuclear industry, on the other hand, administrative procedures play a vital role in assuring the safe operation of a facility. For some time now, industry focus has been on improving technical procedures. Significant efforts are under way to produce technical procedure requires that a validated technical, regulatory, and administrative basis be developed and that the technical process be established for each procedure. Producing usable technical procedures requires that procedure presentation be engineered to the same human factors principles used in control room design. The vital safety role of administrative procedures requires that they be just as sound, just a rigorously formulated, and documented as technical procedures. Procedure programs at the Tennessee Valley Authority and at Boston Edison's Pilgrim Station demonstrate that human factors engineering techniques can be applied effectively to technical procedures. With a few modifications, those same techniques can be used to produce more effective administrative procedures. Efforts are under way at the US Department of Energy Nuclear Weapons Complex and at some utilities (Boston Edison, for instance) to apply human factors engineering to administrative procedures: The techniques being adapted include the following

  14. Human Factors Review Plan

    International Nuclear Information System (INIS)

    Paramore, B.; Peterson, L.R.

    1985-12-01

    ''Human Factors'' is concerned with the incorporation of human user considerations into a system in order to maximize human reliability and reduce errors. This Review Plan is intended to assist in the assessment of human factors conditions in existing DOE facilities. In addition to specifying assessment methodologies, the plan describes techniques for improving conditions which are found to not adequately support reliable human performance. The following topics are addressed: (1) selection of areas for review describes techniques for needs assessment to assist in selecting and prioritizing areas for review; (2) human factors engineering review is concerned with optimizing the interfaces between people and equipment and people and their work environment; (3) procedures review evaluates completeness and accuracy of procedures, as well as their usability and management; (4) organizational interface review is concerned with communication and coordination between all levels of an organization; and (5) training review evaluates training program criteria such as those involving: trainee selection, qualification of training staff, content and conduct of training, requalification training, and program management

  15. Human Factors Review Plan

    Energy Technology Data Exchange (ETDEWEB)

    Paramore, B.; Peterson, L.R. (eds.)

    1985-12-01

    ''Human Factors'' is concerned with the incorporation of human user considerations into a system in order to maximize human reliability and reduce errors. This Review Plan is intended to assist in the assessment of human factors conditions in existing DOE facilities. In addition to specifying assessment methodologies, the plan describes techniques for improving conditions which are found to not adequately support reliable human performance. The following topics are addressed: (1) selection of areas for review describes techniques for needs assessment to assist in selecting and prioritizing areas for review; (2) human factors engineering review is concerned with optimizing the interfaces between people and equipment and people and their work environment; (3) procedures review evaluates completeness and accuracy of procedures, as well as their usability and management; (4) organizational interface review is concerned with communication and coordination between all levels of an organization; and (5) training review evaluates training program criteria such as those involving: trainee selection, qualification of training staff, content and conduct of training, requalification training, and program management.

  16. Human and Organizational Factors

    International Nuclear Information System (INIS)

    Eshiett, P.B.S.

    2016-01-01

    The Human and Organizational Factors Approach to Industrial Safety (HOFS) consists of identifying and putting in place conditions which encourage a positive contribution from operators (individually and in a team) with regards to industrial safety. The knowledge offered by the HOFS approach makes it possible better to understand what conditions human activity and to act on the design of occupational situations and the organization, in the aim of creating the conditions for safe work. Efforts made in this area can also lead to an improvement in results in terms of the quality of production or occupational safety (incidence and seriousness rates) (Daniellou, F., et al., 2011). Research on industrial accidents shows that they rarely happen as a result of a single event, but rather emerge from the accumulation of several, often seemingly trivial, malfunctions, misunderstandings, incorrect assumptions and other issues. The nuclear community has established rigorous international safety standards and concepts to ensure the protection of people and the environment from harmful effects of ionizing radiation (IAEA, 2014). A review of major human induced disasters in a number of countries and in different industries yields insights into several of the human and organizational factors involved in their occurrence. Some of these factors relate to failures in: • Design or technology; • Training; • Decision making; • Communication; • Preparation for the unexpected; • Understanding of organizational interdependencies

  17. Molecular factors in migraine

    Science.gov (United States)

    Kowalska, Marta; Prendecki, Michał; Kozubski, Wojciech; Lianeri, Margarita; Dorszewska, Jolanta

    2016-01-01

    Migraine is a common neurological disorder that affects 11% of adults worldwide. This disease most likely has a neurovascular origin. Migraine with aura (MA) and more common form - migraine without aura (MO) – are the two main clinical subtypes of disease. The exact pathomechanism of migraine is still unknown, but it is thought that both genetic and environmental factors are involved in this pathological process. The first genetic studies of migraine were focused on the rare subtype of MA: familial hemiplegic migraine (FHM). The genes analysed in familial and sporadic migraine are: MTHFR, KCNK18, HCRTR1, SLC6A4, STX1A, GRIA1 and GRIA3. It is possible that migraine is a multifactorial disease with polygenic influence. Recent studies have shown that the pathomechanisms of migraine involves both factors responsible for immune response and oxidative stress such as: cytokines, tyrosine metabolism, homocysteine; and factors associated with pain transmission and emotions e.g.: serotonin, hypocretin-1, calcitonin gene-related peptide, glutamate. The correlations between genetic variants of the HCRTR1 gene, the polymorphism 5-HTTLPR and hypocretin-1, and serotonin were observed. It is known that serotonin inhibits the activity of hypocretin neurons and may affect the appearance of the aura during migraine attack. The understanding of the molecular mechanisms of migraine, including genotype-phenotype correlations, may contribute to finding markers important for the diagnosis and treatment of this disease. PMID:27191890

  18. Structuring factoring business: accounting aspects

    Directory of Open Access Journals (Sweden)

    I.M. Vygivska

    2017-08-01

    Full Text Available The article theoretically substantiates the fact that factoring belongs to the main operational activity of a factoring company, and this allowed structuring the factoring business by types of activity. The lack of a unified approach to the classification of factoring (factoring services made it possible to systematize and refine their classification as a basis for developing accounting and analytical support for risk management of factoring business. The authors single out such classification signs as: the right of the reverse claim (reverse, irretrievable, a territorial feature (international, internal, the subject of the factoring contract (real, consensual, the availability of notification of the debtor (conventional, confidential. The structuring of factoring business contributes to the identification of the risks of the economic activities of a factoring company depending on the type of factoring, the development of methodological support for the bookkeeping of factoring transactions in a risk environment, the search for risk management practices and the determination of management effectiveness in general.

  19. Milestones and Impact Factors

    Directory of Open Access Journals (Sweden)

    Grandjean Philippe

    2010-07-01

    Full Text Available Abstract Environmental Health has just received its first Impact Factor by Thomson ISI. At a level of 2.48, this achievement is quite satisfactory and places Environmental Health in the top 25% of environmental science journals. When the journal was launched in 2002, it was still unclear whether the Open Access publishing model could be made into a viable commercial enterprise within the biomedical field. During the past eight years, Open Access journals have become widely available, although still covering only about 15% of journal titles. Major funding agencies and institutions, including prominent US universities, now require that researchers publish in Open Access journals. Because of the profound role of scientific journals for the sharing of results and communication between researchers, the advent of Open Access may be of as much significance as the transition from handwriting to printing via moveable type. As Environmental Health is an electronic Open Access journal, the numbers of downloads at the journal website can be retrieved. The top-20 list of articles most frequently accessed shows that all of them have been downloaded over 10,000 times. Back in 2002, the first article published was accessed only 49 times during the following month. A year later, the server had over 1,000 downloads per month, and now the total number of monthly downloads approaches 50,000. These statistics complement the Impact Factor and confirm the viability of Open Access in our field of research. The advent of digital media and its decentralized mode of distribution - the internet - have dramatically changed the control and financing of scientific information dissemination, while facilitating peer review, accelerating editorial handling, and supporting much needed transparency. Both the meaning and means of "having an impact" are therefore changing, as will the degree and way in which scientific journals remain "factors" in that impact.

  20. Factor 4 planning

    International Nuclear Information System (INIS)

    Bariol-Mathais, Brigitte; Lavoillotte, Philippine; Gall-Sorrentino, Florence; Malez, Marianne; Sanna, Daniela; Marsauche, Maud; Marquet, Sarah; Debergue, Sophie; Aminu, Olufunmi; Bernard, Helene; Marchand, Jean-Michel; Blin, Frederic; Grange, Jerome; Caillierez, Sophie; Muller, Dania; Clement, Bob; Desire, Jean-Charles; Metais, Benedicte; Lannuzel, Philippe; Pezet-Kuhn, Murielle; Pons, Anne; Rivoire-Meley, Benedicte; Tissot, Heloise

    2015-07-01

    Factor 4 is the goal of cutting our greenhouse gas emissions by 75% by 2050. Achieving this objective will necessitate radical changes in our practices, in particular concerning transport and housing; the measures currently implemented, such as positive-energy buildings, low-impact mobility and eco-neighbourhoods, will not be enough to meet this goal. These measures must be conceived in the framework of broad territorial planning that integrates environmental and energy objectives far upstream. To this end, the French Environment and Energy Management Agency (ADEME) and the French network of Urban Planning Agencies (FNAU), pursuing their missions in their respective areas of competence, have joined forces to make infrastructure and land use planning an integral part of the environmental and energy transition process. In 2013, the two organisations signed a partnership agreement and compiled an inventory of practices that are relevant to Factor 4 planning. This work was led by Epures, Saint-etienne urban planning agency, along with FNAU, drawing upon the expertise of a dozen urban planning agencies in precursor territories. This inventory describes the stakes, resources and strengths for each territory, which have led to cross-sectoral territorial planning exercises with ambitious environmental and energy objectives; the importance of evaluation in attaining these goals is emphasised. Current experience, questions and available methodological tools are summarised in this document, to encourage territories and help them design their planning policies along a trajectory to achieve Factor 4 goals. The compilation also aims to be a contribution to the COP21 climate conference

  1. Accidents and human factors

    International Nuclear Information System (INIS)

    Nishiwaki, Y.; Kawai, H.; Morishima, H.; Terano, T.; Sugeno, M.

    1984-01-01

    When the TMI accident occurred it was 4 a.m., an hour when the error potential of the operators would have been very high. The frequency of car and train accidents in Japan is also highest between 4 a.m. and 6 a.m. The error potential may be classified into five phases corresponding to the electroencephalogramic pattern (EEG). At phase 0, when the delta wave appears, a person is unconscious and in deep sleep; at phase I, when the theta wave appears, he is very tired, sleepy and subnormal; at phase II, when the alpha wave appears, he is normal, relaxed and passive; at phase III, when the beta wave appears, he is normal, clear-minded and active; at phase IV, when the strong beta or epileptic wave appears, he is hypernormal, excited and incapable of normal judgement. Should an accident occur at phase II, the brain condition may jump to phase IV. At this phase the error or accident potential is maximum. The response of the human brain to different types of noises and signals may vary somewhat for different individuals and for different groups of people. Therefore, the possibility that such differences in brain functions may influence the mental structure would be worthy of consideration in human factors and in the design of man-machine systems. Human reliability and performance would be affected by many factors: medical, physiological and psychological, etc. The uncertainty involved in human factors may not necessarily be probabilistic, but fuzzy. Therefore, it would be important to develop a theory by which both non-probabilistic uncertainties, or fuzziness, of human factors and the probabilistic properties of machines can be treated consistently. From the mathematical point of view, probabilistic measure is considered a special case of fuzzy measure. Therefore, fuzzy set theory seems to be an effective tool for analysing man-machine systems. To minimize human error and the possibility of accidents, new safety systems should not only back up man and make up for his

  2. Speeding Fermat's factoring method

    Science.gov (United States)

    McKee, James

    A factoring method is presented which, heuristically, splits composite n in O(n^{1/4+epsilon}) steps. There are two ideas: an integer approximation to sqrt(q/p) provides an O(n^{1/2+epsilon}) algorithm in which n is represented as the difference of two rational squares; observing that if a prime m divides a square, then m^2 divides that square, a heuristic speed-up to O(n^{1/4+epsilon}) steps is achieved. The method is well-suited for use with small computers: the storage required is negligible, and one never needs to work with numbers larger than n itself.

  3. Improved Balanced Incomplete Factorization

    Czech Academy of Sciences Publication Activity Database

    Bru, R.; Marín, J.; Mas, J.; Tůma, Miroslav

    2010-01-01

    Roč. 31, č. 5 (2010), s. 2431-2452 ISSN 0895-4798 R&D Projects: GA AV ČR IAA100300802 Grant - others:GA AV ČR(CZ) M100300902 Institutional research plan: CEZ:AV0Z10300504 Source of funding: I - inštitucionálna podpora na rozvoj VO Keywords : preconditioned iterative methods * sparse matrices * incomplete decompositions * approximate inverses * Sherman-Morrison formula * nonsymmetric matrices Subject RIV: BA - General Mathematics Impact factor: 1.725, year: 2010

  4. Sleep-inducing factors.

    Science.gov (United States)

    García-García, Fabio; Acosta-Peña, Eva; Venebra-Muñoz, Arturo; Murillo-Rodríguez, Eric

    2009-08-01

    Kuniomi Ishimori and Henri Piéron were the first researchers to introduce the concept and experimental evidence for a chemical factor that would presumably accumulate in the brain during waking and eventually induce sleep. This substance was named hypnotoxin. Currently, the variety of substances which have been shown to alter sleep includes peptides, cytokines, neurotransmitters and some substances of lipidic nature, many of which are well known for their involvement in other biological activities. In this chapter, we describe the sleep-inducing properties of the vasoactive intestinal peptide, prolactin, adenosine and anandamide.

  5. "Factor Analysis Using ""R"""

    Directory of Open Access Journals (Sweden)

    A. Alexander Beaujean

    2013-02-01

    Full Text Available R (R Development Core Team, 2011 is a very powerful tool to analyze data, that is gaining in popularity due to its costs (its free and flexibility (its open-source. This article gives a general introduction to using R (i.e., loading the program, using functions, importing data. Then, using data from Canivez, Konold, Collins, and Wilson (2009, this article walks the user through how to use the program to conduct factor analysis, from both an exploratory and confirmatory approach.

  6. Perinatal risk factors for strabismus

    DEFF Research Database (Denmark)

    Torp-Pedersen, Tobias; Boyd, Heather A; Poulsen, Gry

    2010-01-01

    Little is known about the aetiological factors underlying strabismus. We undertook a large cohort study to investigate perinatal risk factors for strabismus, overall and by subtype.......Little is known about the aetiological factors underlying strabismus. We undertook a large cohort study to investigate perinatal risk factors for strabismus, overall and by subtype....

  7. Activation of human factor V by factor Xa and thrombin

    International Nuclear Information System (INIS)

    Monkovic, D.D.; Tracy, P.B.

    1990-01-01

    The activation of human factor V by factor Xa and thrombin was studied by functional assessment of cofactor activity and sodium dodecyl sulfate-polycarylamide gel electrophoresis followed by either autoradiography of 125 I-labeled factor V activation products or Western blot analyses of unlabeled factor V activation products. Cofactor activity was measured by the ability of the factor V/Va peptides to support the activation of prothrombin. The factor Xa catalyzed cleavage of factor V was observed to be time, phospholipid, and calcium ion dependent, yielding a cofactor with activity equal to that of thrombin-activated factor V (factor Va). The cleavage pattern differed markedly from the one observed in the bovine system. The factor Xa activated factor V subunits expressing cofactor activity were isolated and found to consist of peptides of M r 220,000 and 105,000. Although thrombin cleaved the M r 220,000 peptide to yield peptides previously shown to be products of thrombin activation, cofactor activity did not increase. N-Terminal sequence analysis confirmed that both factor Xa and thrombin cleave factor V at the same bond to generate the M r 220,000 peptide. The factor Xa dependent functional assessment of 125 I-labeled factor V coupled with densitometric analyses of the cleavage products indicated that the cofactor activity of factor Xa activated factor V closely paralleled the appearance of the M r 220,000 peptide. The data indicate that factor Xa is as efficient an enzyme toward factor V as thrombin

  8. Organizational factors in Korean NPPs

    International Nuclear Information System (INIS)

    Jang, D. J.; Kim, Y. I.; Jeong, C. H.; Kim, J. W.

    2003-01-01

    Organizational factors are referred to as the factors that influence the achievement of a goal of an organization. Latent problems of an organization could contribute to causing human errors in such stages as design, operation and maintenance, and furthermore, leading to an severe accident. In order to evaluate an organization from the safety viewpoint, it is necessary to identify the organizational factors in a systematic fashion. In this paper, some efforts to identify the organizational factors in Korean NPPs are presented. The study was performed in the following steps: 1) Reviewing the definitions and range of the organizational factors used by the previous 13 researches, 2) Structuring the organizational factors by screening and collating factors, 3) Analysing the organizational factors that is considered to have contributed to the trip events based on the trip report of Korean NPPs, 4) Suggesting a more reliable taxonomy of organizational factors for event analysis by applying the Onion Structure Model to the selected factors

  9. Risk Factors in Pemphigus

    Directory of Open Access Journals (Sweden)

    Gülşen Tükenmez Demirc

    2011-09-01

    Full Text Available Background and Design: There have been reports suggesting the involvement of environmental factors in the disease process of pemphigus. In this study, we aimed to find out the risk factors which could play role in the etiopathogenesis in our pemphigus patients.Material and method: A total of 42 patients (15 male and 27 female who were diagnosed as pemphigus with histopathological and direct immunoflurosence examinations in our clinic between the years 1998-2004, were interviewed for assessment of regarding with the subjects of the demographic properties, occupational groups, educational level, the number of pregnancies, stressfull life events, diet habits, smoking and alcohol consumption before the onset of the disease and the results were compared to 42 age and gender-matched controls with similar socioeconomic circumstances. Results: Working in agriculture and livestock, multi-parity, absence of smoking and stressfull life events were found to be statistically significant in pemphigus patients than in controls. Conclusion: Working in agriculture and livestock, multi-parity, absence of smoking and stressfull life events were assumed to play role in the etiopathogenesis and course of pemphigus.

  10. Activation of 125I-Factor IX and 125I-Factor X: Effect of tissue factor and Factor VII, Factor Xsub(a) and thrombin

    International Nuclear Information System (INIS)

    Oesterud, B.; Rapaport, S.I.

    Activation of Factor IX and Factor X was studied by adding 125 I-Factor IX or 125 I-Factor X to reaction mixtures and quantitating cleavage products by reduced sodium dodecylsulfate gel electrophoresis. Thrombin failed to activate Factors IX or X; Factor Xsub(a) produced insignificant amounts of cleavage products of both factors. In contrast, the reaction product of tissue factor and Factor VII cleaved large amounts of both Factor IX and Factor X in purified systems and in plasma. In incubation mixtures of plasma containing added 125 I-Factor IX or 125 I-Factor X, tissue factor and Ca 2+ ions, the percentage of total radioactivity in the heavy chain peak of 125 I-IXsub(a) and the heavy chain of 125 I-Xsub(a) increased at a similar rate. When the tissue factor was diluted, similar curves were obtained for percent cleavage of 125 I-Factor IX and percent cleavage of 125 I-Factor X plotted against tissue factor concentration. These findings support the hypothesis that activation of Factor IX by the tissue factor-Factor VII reaction product represents a physiologically significant step in normal haemostasis. (author)

  11. Psychosomatic factors in pruritus.

    Science.gov (United States)

    Tey, Hong Liang; Wallengren, Joanna; Yosipovitch, Gil

    2013-01-01

    Pruritus and psyche are intricately and reciprocally related, with psychophysiological evidence and psychopathological explanations helping us to understand their complex association. Their interaction may be conceptualized and classified into 3 groups: pruritic diseases with psychiatric sequelae, pruritic diseases aggravated by psychosocial factors, and psychiatric disorders causing pruritus. Management of chronic pruritus is directed at treating the underlying causes and adopting a multidisciplinary approach to address the dermatologic, somatosensory, cognitive, and emotional aspects. Pharmcotherapeutic agents that are useful for chronic pruritus with comorbid depression and/or anxiety comprise selective serotonin reuptake inhibitors, mirtazapine, tricyclic antidepressants (amitriptyline and doxepin), and anticonvulsants (gabapentin, pregabalin); the role of neurokinin receptor-1 antagonists awaits verification. Antipsychotics are required for treating itch and formication associated with schizophrenia and delusion of parasitosis (including Morgellons disease). Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Factorization of Observables

    Science.gov (United States)

    Eliaš, Peter; Frič, Roman

    2017-12-01

    Categorical approach to probability leads to better understanding of basic notions and constructions in generalized (fuzzy, operational, quantum) probability, where observables—dual notions to generalized random variables (statistical maps)—play a major role. First, to avoid inconsistencies, we introduce three categories L, S, and P, the objects and morphisms of which correspond to basic notions of fuzzy probability theory and operational probability theory, and describe their relationships. To illustrate the advantages of categorical approach, we show that two categorical constructions involving observables (related to the representation of generalized random variables via products, or smearing of sharp observables, respectively) can be described as factorizing a morphism into composition of two morphisms having desired properties. We close with a remark concerning products.

  13. Functional Maximum Autocorrelation Factors

    DEFF Research Database (Denmark)

    Larsen, Rasmus; Nielsen, Allan Aasbjerg

    2005-01-01

    MAF outperforms the functional PCA in concentrating the interesting' spectra/shape variation in one end of the eigenvalue spectrum and allows for easier interpretation of effects. Conclusions. Functional MAF analysis is a useful methods for extracting low dimensional models of temporally or spatially......Purpose. We aim at data where samples of an underlying function are observed in a spatial or temporal layout. Examples of underlying functions are reflectance spectra and biological shapes. We apply functional models based on smoothing splines and generalize the functional PCA in......\\verb+~+\\$\\backslash\\$cite{ramsay97} to functional maximum autocorrelation factors (MAF)\\verb+~+\\$\\backslash\\$cite{switzer85,larsen2001d}. We apply the method to biological shapes as well as reflectance spectra. {\\$\\backslash\\$bf Methods}. MAF seeks linear combination of the original variables that maximize autocorrelation between...

  14. Pion form factor

    Energy Technology Data Exchange (ETDEWEB)

    Ryong Ji, C.; Pang, A.; Szczepaniak, A. [North Carolina State Univ., Raleigh, NC (United States)

    1994-04-01

    It is pointed out that the correct criterion to define the legal PQCD contribution to the exclusive processes in the lightcone perturbative expansion should be based on the large off-shellness of the lightcone energy in the intermediate states. In the lightcone perturbative QCD calculation of the pion form factor, the authors find that the legal PQCD contribution defined by the lightcone energy cut saturates in the smaller Q{sup 2} region compared to that defined by the gluon four-momentum square cut. This is due to the contribution by the highly off-energy-shell gluons in the end point regions of the phase space, indicating that the gluon four-momentum-square cut may have cut too much to define the legal PQCD.

  15. Eukaryotic transcription factors

    DEFF Research Database (Denmark)

    Staby, Lasse; O'Shea, Charlotte; Willemoës, Martin

    2017-01-01

    Gene-specific transcription factors (TFs) are key regulatory components of signaling pathways, controlling, for example, cell growth, development, and stress responses. Their biological functions are determined by their molecular structures, as exemplified by their structured DNA-binding domains...... regions with function-related, short sequence motifs and molecular recognition features with structural propensities. This review focuses on molecular aspects of TFs, which represent paradigms of ID-related features. Through specific examples, we review how the ID-associated flexibility of TFs enables....... It is furthermore emphasized how classic biochemical concepts like allostery, conformational selection, induced fit, and feedback regulation are undergoing a revival with the appreciation of ID. The review also describes the most recent advances based on computational simulations of ID-based interaction mechanisms...

  16. Nucleon Electromagnetic Form Factors

    Energy Technology Data Exchange (ETDEWEB)

    Marc Vanderhaeghen; Charles Perdrisat; Vina Punjabi

    2007-10-01

    There has been much activity in the measurement of the elastic electromagnetic proton and neutron form factors in the last decade, and the quality of the data has greatly improved by performing double polarization experiments, in comparison with previous unpolarized data. Here we review the experimental data base in view of the new results for the proton, and neutron, obtained at JLab, MAMI, and MIT-Bates. The rapid evolution of phenomenological models triggered by these high-precision experiments will be discussed, including the recent progress in the determination of the valence quark generalized parton distributions of the nucleon, as well as the steady rate of improvements made in the lattice QCD calculations.

  17. Wave friction factor rediscovered

    Science.gov (United States)

    Le Roux, J. P.

    2012-02-01

    The wave friction factor is commonly expressed as a function of the horizontal water particle semi-excursion ( A wb) at the top of the boundary layer. A wb, in turn, is normally derived from linear wave theory by {{U_{{wb}}/T_{{w}}}}{{2π }} , where U wb is the maximum water particle velocity measured at the top of the boundary layer and T w is the wave period. However, it is shown here that A wb determined in this way deviates drastically from its real value under both linear and non-linear waves. Three equations for smooth, transitional and rough boundary conditions, respectively, are proposed to solve this problem, all three being a function of U wb, T w, and δ, the thickness of the boundary layer. Because these variables can be determined theoretically for any bottom slope and water depth using the deepwater wave conditions, there is no need to physically measure them. Although differing substantially from many modern attempts to define the wave friction factor, the results coincide with equations proposed in the 1960s for either smooth or rough boundary conditions. The findings also confirm that the long-held notion of circular water particle motion down to the bottom in deepwater conditions is erroneous, the motion in fact being circular at the surface and elliptical at depth in both deep and shallow water conditions, with only horizontal motion at the top of the boundary layer. The new equations are incorporated in an updated version (WAVECALC II) of the Excel program published earlier in this journal by Le Roux et al. Geo-Mar Lett 30(5): 549-560, (2010).

  18. [The Steel factor].

    Science.gov (United States)

    Cáceres-Cortés, J R

    1997-01-01

    Mice bearing mutations at either of two loci, dominant White spotting(W) or Steel(Sl), exhibit development defects in hematopoietic, melanocytic and germ cells. Genetics studies have shown that the SI locus encodes the Steel factor (SF), which is the ligand for the tyrosine kinase receptor c-kit, the product of the W locus. SF is synthesized in membrane-bound form and can be processed to produce a soluble form. Cell-cell interaction is important in the production of normal blood cells in vivo and in vitro and in the cellular expansion of leukemic cells. We discuss here how SF decreases the requirements in cell interaction for blast colony formation in acute myeloblastic leukemia (AML) and the presence of membrane-bound SF possibly contributes to the density-dependent growth of the AML blasts. We explain that SF is mainly a survival factor for hematopoietic cells, of little proliferative effect, which maintains CD34+ hematopoietic cells in an undifferentiated state. These properties would potentially allow the maintenance of hematopoietic cells in culture for the purpose of marrow purging or gene therapy. The activation of the c-kit signal transduction pathway may play a significant role in the development of many types of non-hematological malignancies by disrupting normal cell-cell interactions and allowing the growth of cancer cell populations. In summary, the properties of the SF indicate it has a role for survival signals during the process of normal differentiation, AML proliferation and in the maintenance of many c-kit+ tumors.

  19. Neutron quality factor

    International Nuclear Information System (INIS)

    1995-06-01

    Both the International Commission on Radiological Protection (ICRP) and the National Council on Radiation Protection and Measurements (NCRP) have recommended that the radiation quality weighting factor for neutrons (Q n , or the corresponding new modifying factor, w R ) be increased by a value of two for most radiation protection practices. This means an increase in the recommended value for Q n from a nominal value of 10 to a nominal value of 20. This increase may be interpreted to mean that the biological effectiveness of neutrons is two times greater than previously thought. A decision to increase the value of Q n will have a major impact on the regulations and radiation protection programs of Federal agencies responsible for the protection of radiation workers. Therefore, the purposes of this report are: (1) to examine the general concept of open-quotes quality factorclose quotes (Q) in radiation protection and the rationale for the selection of specific values of Q n ; and (2) to make such recommendations to the Federal agencies, as appropriate. This report is not intended to be an exhaustive review of the scientific literature on the biological effects of neutrons, with the aim of defending a particular value for Q n . Rather, the working group examined the technical issues surrounding the current recommendations of scientific advisory bodies on this matter, with the aim of determining if these recommendations should be adopted by the Federal agencies. Ultimately, the group concluded that there was no compelling basis for a change in Q n . The report was prepared by Federal scientists working under the auspices of the Science Panel of the Committee on Interagency Radiation Research and Policy Coordination (CIRRPC)

  20. Factorization and non-factorization in diffractive hard scattering

    International Nuclear Information System (INIS)

    Berera, Arjun

    1997-01-01

    Factorization, in the sense defined for inclusive hard scattering, is discussed for diffractive hard scattering. A factorization theorem similar to its inclusive counterpart is presented for diffractive DIS. For hadron-hadron diffractive hard scattering, in contrast to its inclusive counterpart, the expected breakdown of factorization is discussed. Cross section estimates are given from a simple field theory model for non-factorizing double-pomeron-exchange (DPE) dijet production with and without account for Sudakov suppression

  1. Robust and Sparse Factor Modelling

    DEFF Research Database (Denmark)

    Croux, Christophe; Exterkate, Peter

    Factor construction methods are widely used to summarize a large panel of variables by means of a relatively small number of representative factors. We propose a novel factor construction procedure that enjoys the properties of robustness to outliers and of sparsity; that is, having relatively few...... nonzero factor loadings. Compared to the traditional factor construction method, we find that this procedure leads to a favorable forecasting performance in the presence of outliers and to better interpretable factors. We investigate the performance of the method in a Monte Carlo experiment...

  2. Identifying the important factors in simulation models with many factors

    NARCIS (Netherlands)

    Bettonvil, B.; Kleijnen, J.P.C.

    1994-01-01

    Simulation models may have many parameters and input variables (together called factors), while only a few factors are really important (parsimony principle). For such models this paper presents an effective and efficient screening technique to identify and estimate those important factors. The

  3. External Factors, Internal Factors and Self-Directed Learning Readiness

    Science.gov (United States)

    Ramli, Nurjannah; Muljono, Pudji; Afendi, Farit M.

    2018-01-01

    There are many factors which affect the level of self-directed learning readiness. This study aims to investigate the relationship between external factors, internal factors and self-directed learning readiness. This study was carried out by using a census method for fourth year students of medical program of Tadulako University. Data were…

  4. Electromagnetic Hadronic Form-Factors

    International Nuclear Information System (INIS)

    Edwards, Robert G.

    2005-01-01

    We present a calculation of the nucleon electromagnetic form-factors as well as the pion and rho to pion transition form-factors in a hybrid calculation with domain wall valence quarks and improved staggered (Asqtad) sea quarks

  5. R-Factor for Alaska

    Data.gov (United States)

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

  6. Air Emissions Factors and Quantification

    Science.gov (United States)

    Emissions factors are used in developing air emissions inventories for air quality management decisions and in developing emissions control strategies. This area provides technical information on and support for the use of emissions factors.

  7. Integrated Factors Correlating Undergraduate Academic ...

    African Journals Online (AJOL)

    Integrated Factors Correlating Undergraduate Academic Achievement in Bayelsa State, Nigeria. ... AFRREV IJAH: An International Journal of Arts and Humanities ... Thus, it is study investigated the integrated factors determining academic performance of students in public secondary schools in Bayelsa State, Nigeria.

  8. Downregulation of the Hsp90 system causes defects in muscle cells of Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Andreas M Gaiser

    Full Text Available The ATP-dependent molecular chaperone Hsp90 is required for the activation of a variety of client proteins involved in various cellular processes. Despite the abundance of known client proteins, functions of Hsp90 in the organismal context are not fully explored. In Caenorhabditis elegans, Hsp90 (DAF-21 has been implicated in the regulation of the stress-resistant dauer state, in chemosensing and in gonad formation. In a C. elegans strain carrying a DAF-21 mutation with a lower ATP turnover, we observed motility defects. Similarly, a reduction of DAF-21 levels in wild type nematodes leads to reduced motility and induction of the muscular stress response. Furthermore, aggregates of the myosin MYO-3 are visible in muscle cells, if DAF-21 is depleted, implying a role of Hsp90 in the maintenance of muscle cell functionality. Similar defects can also be observed upon knockdown of the Hsp90-cochaperone UNC-45. In life nematodes YFP-DAF-21 localizes to the I-band and the M-line of the muscular ultrastructure, but the protein is not stably attached there. The Hsp90-cofactor UNC-45-CFP contrarily can be found in all bands of the nematode muscle ultrastructure and stably associates with the UNC-54 containing A-band. Thus, despite the physical interaction between DAF-21 and UNC-45, apparently the two proteins are not always localized to the same muscular structures. While UNC-45 can stably bind to myofilaments in the muscular ultrastructure, Hsp90 (DAF-21 appears to participate in the maintenance of muscle structures as a transiently associated diffusible factor.

  9. Genes that act downstream of sensory neurons to influence longevity, dauer formation, and pathogen responses in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Marta M Gaglia

    Full Text Available The sensory systems of multicellular organisms are designed to provide information about the environment and thus elicit appropriate changes in physiology and behavior. In the nematode Caenorhabditis elegans, sensory neurons affect the decision to arrest during development in a diapause state, the dauer larva, and modulate the lifespan of the animals in adulthood. However, the mechanisms underlying these effects are incompletely understood. Using whole-genome microarray analysis, we identified transcripts whose levels are altered by mutations in the intraflagellar transport protein daf-10, which result in impaired development and function of many sensory neurons in C. elegans. In agreement with existing genetic data, the expression of genes regulated by the transcription factor DAF-16/FOXO was affected by daf-10 mutations. In addition, we found altered expression of transcriptional targets of the DAF-12/nuclear hormone receptor in the daf-10 mutants and showed that this pathway influences specifically the dauer formation phenotype of these animals. Unexpectedly, pathogen-responsive genes were repressed in daf-10 mutant animals, and these sensory mutants exhibited altered susceptibility to and behavioral avoidance of bacterial pathogens. Moreover, we found that a solute transporter gene mct-1/2, which was induced by daf-10 mutations, was necessary and sufficient for longevity. Thus, sensory input seems to influence an extensive transcriptional network that modulates basic biological processes in C. elegans. This situation is reminiscent of the complex regulation of physiology by the mammalian hypothalamus, which also receives innervations from sensory systems, most notably the visual and olfactory systems.

  10. Insulin Signaling in the Aging of Healthy and Proteotoxically Stressed Mechanosensory Neurons

    Directory of Open Access Journals (Sweden)

    Courtney eScerbak

    2014-07-01

    Full Text Available Insulin signaling is central to cellular metabolism and organismal aging. However, the role of insulin signaling in natural and proteotoxically stressed aging neurons has yet to be fully described. We studied aging of Caenorbaditis elegans mechanosensory neurons expressing a neurotoxic expanded polyglutamine transgene (polyQ128, or lacking this proteotoxicity stressor (polyQ0, under conditions in which the insulin signaling pathway was disrupted by RNA interference (RNAi. We describe specific changes in lifespan, mechanosensory neuronal morphologies, and mechansensory function following RNAi treatment targeting the insulin signaling pathway. Overall, we confirmed that transcription factor DAF-16 is neuroprotective in the proteotoxically stressed model, though not strikingly in the naturally aging model. Decreased insulin signaling through daf-2 RNAi improved mechanosensory function in both models and decreased protein aggregation load in polyQ128, yet showed opposing effects on accumulation of neuronal aberrations in both strains. Decreased daf-2 signaling slightly enhanced mechanosensation while greatly enhancing branching of the mechanosensory neuron axons and dendrites in polyQ0 animals, suggesting that branching is an adaptive response in natural aging. These effects in polyQ0 did not appear to involve DAF-16, suggesting the existence of a non-canonical DAF-2 pathway for the modulation of morphological adaptation. However, in polyQ128 animals, decreased daf-2 signaling significantly enhanced mechanosensation while decreasing neuronal aberrations. Unlike other interventions that reduce the strength of insulin signaling, daf-2 RNAi dramatically redistributed large polyQ128 aggregates to the cell body, away from neuronal processes. Our results suggest that insulin signaling strength can differentially affect specific neurons aging naturally or under proteotoxic stress.

  11. Human Factors in Training

    Science.gov (United States)

    Barshi, Immanuel; Byrne, Vicky; Arsintescu, Lucia; Connell, Erin

    2010-01-01

    Future space missions will be significantly longer than current shuttle missions and new systems will be more complex than current systems. Increasing communication delays between crews and Earth-based support means that astronauts need to be prepared to handle the unexpected on their own. As crews become more autonomous, their potential span of control and required expertise must grow to match their autonomy. It is not possible to train for every eventuality ahead of time on the ground, or to maintain trained skills across long intervals of disuse. To adequately prepare NASA personnel for these challenges, new training approaches, methodologies, and tools are required. This research project aims at developing these training capabilities. By researching established training principles, examining future needs, and by using current practices in space flight training as test beds, both in Flight Controller and Crew Medical domains, this research project is mitigating program risks and generating templates and requirements to meet future training needs. Training efforts in Fiscal Year 09 (FY09) strongly focused on crew medical training, but also began exploring how Space Flight Resource Management training for Mission Operations Directorate (MOD) Flight Controllers could be integrated with systems training for optimal Mission Control Center (MCC) operations. The Training Task addresses Program risks that lie at the intersection of the following three risks identified by the Project: 1) Risk associated with poor task design; 2) Risk of error due to inadequate information; and 3) Risk associated with reduced safety and efficiency due to poor human factors design.

  12. Self-shielding factors

    International Nuclear Information System (INIS)

    Kaul, D.C.

    1982-01-01

    Throughout the last two decades many efforts have been made to estimate the effect of body self-shielding on organ doses from externally incident neutrons and gamma rays. These began with the use of simple geometry phantoms and have culminated in the use of detailed anthropomorphic phantoms. In a recent effort, adjoint Monte Carlo analysis techniques have been used to determine dose and dose equivalent to the active marrow as a function of energy and angle of neutron fluence externally incident on an anthropomorphic phantom. When combined with fluences from actual nuclear devices, these dose-to-fluence factors result in marrow dose values that demonstrate great sensitivity to variations in device type, range, and body orientation. Under a state-of-the-art radiation transport analysis demonstration program for the Japanese cities, sponsored by the Defense Nuclear Agency at the request of the National Council on Radiation Protection and Measurements, the marrow dose study referred to above is being repeated to obtain spectral distributions within the marrow for externally incident neutrons and gamma rays of arbitrary energy and angle. This is intended to allow radiobiologists and epidemiologists to select and to modify numbers of merit for correlation with health effects and to permit a greater understanding of the relationship between human and laboratory subject dosimetry

  13. Research organizational factors

    International Nuclear Information System (INIS)

    Coffman, F.D. Jr.

    1990-01-01

    Organizational processes at nuclear power plants should be sufficient to prevent accidents and to protect public health and safety upon the occurrence of an accident. The role of regulatory research is to confirm that agency assessments of organization processes are on a firm technical basis and provide for improvements in the NRC [Nuclear Regulatory Commission] programs. A firm technical basis is achieved by reducing uncertainties associated with methods and measures used to assess organization processes. The general objective for regulatory research is to confirm that the agency has a coherent understanding of the organizational processes that are individually necessary and are collectively sufficient for safe operations, methods are available to reliably characterize organizational processes, and measures exist to monitor changes in the key organizational processes. The first specific objective was to develop a method to translate organizational processes into PRAs. The discussion provides feedback and insights from experience with the past and the ongoing organizational factors research. That experience suggests a set of ingredients that appear proper for performing regulatory research on organizational processes. By keeping focused upon these proper ingredients, the research will contribute to the regulatory assessments of utility management through the use of improved methods and measures in investigations, inspections, diagnostics, performance indicators, and PRA insights

  14. BASIC FACTORS OF MARKET CONCENTRATION

    OpenAIRE

    V. Fyliuk

    2013-01-01

    The paper systemizes factors which reinforce trends towards market concentration in all economic systems. These factors include factors related to the general changes in economic environment such as globalization of the world economy, state structural and taxation policies, cycle of economic development and changes in consumer demand. They also include factors related to competition (intensification of competition, companies’ desire to monopolize market and present market structure) and scien...

  15. Human Factors in Marine Casualties

    Directory of Open Access Journals (Sweden)

    Jelenko Švetak

    2002-05-01

    Full Text Available Human factors play an important role in the origin of accidents,and it is commonly claimed that between seventy andninety-five percent of industrial and transport accidents involvehuman factors, see Figure 1.Some authorities, however, claim that ultimately, all accidentsinvolve human factors.

  16. Risks factoring business: accounting measurement

    Directory of Open Access Journals (Sweden)

    Z.V. Gutsaylyuk

    2015-06-01

    Full Text Available The paper carried out the identification of risk factors for the development of possible accounting software management. Studied theoretical and methodological aspects of the risk classification of factoring operations in the part of the risk assessment factors. It is proposed to consider the risks factors as the risk that is acceptable controlled by accounting instruments and the risks that can not be taken into account in the accounting records. To minimize the risk factor, accounting-driven tools, a method of self-insurance, which is a factor in the creation of provision for factoring transactions designed to cover unexpected expenses and losses. Provision for factoring factor will establish more stable conditions of financial activity and avoid the fluctuations of profit factor in relation to the writing off of losses on factoring operatsіyam.Developed proposals allow for further research to improve the organizational and methodological basis of accounting and analysis of information as a basis for providing risk management factor, particularly in terms of improving the evaluation questions such risks and their qualitative and quantitative analysis.

  17. Investing in systematic factor premiums

    NARCIS (Netherlands)

    Koedijk, Kees G.; Slager, Alfred M. H.; Stork, P.A.

    In this paper we investigate and evaluate factor investing in the US and Europe for equities and bonds. We show that factor-based portfolios generally produce comparable or better portfolios than market indices. We expand the analysis to other asset classes and factors, work with other optimisation

  18. Sparse and Robust Factor Modelling

    NARCIS (Netherlands)

    C. Croux (Christophe); P. Exterkate (Peter)

    2011-01-01

    textabstractFactor construction methods are widely used to summarize a large panel of variables by means of a relatively small number of representative factors. We propose a novel factor construction procedure that enjoys the properties of robustness to outliers and of sparsity; that is, having

  19. Risk Factor Assessment Branch (RFAB)

    Science.gov (United States)

    The Risk Factor Assessment Branch (RFAB) focuses on the development, evaluation, and dissemination of high-quality risk factor metrics, methods, tools, technologies, and resources for use across the cancer research continuum, and the assessment of cancer-related risk factors in the population.

  20. Geriatic Disability Related Factors

    Directory of Open Access Journals (Sweden)

    Mohsen Adib Hajbagheri

    2008-07-01

    Full Text Available Objectives: Reports are indicating of increasing trend of aging and disability in the developing countries while such disabilities are decreasing within the developed countries. This study designed to evaluate the disability and some of its related factors among the elderly population (65 and older in Kashan, Iran. Methods & Materials: A cross-sectional analytical study was conducted on a multi-stage random sample of 350 elderly people (65 year and older in Kashan. The WHO-DAS-II was used as the generic disability measure. The questionnair had 48 questions. The range of score could be between 0-144. Chi-square, t-test analysis and ANOVA were utilized to check significant differences between subgroups. Results: 61% were men and 12% were living lonely. One fourth had some type of addiction, the majority were ilitrate and two thired had not regular phisycal activity.Twenty percent of the old people had a modereate disability and 4.3% were extremely disabled. A significant relationship was found between the disability and variables such as sex, age, living style, needing help, marriage status, living location, addiction, job, level of physical activity, education, and having multiple diseases. Conclusion: In conclusion, geriatric population in Iran, has a lower levels of disability in compare to those of other developed countries. Need of geriatric cares must be be increasing, since the populationpattern of elderly people is increasing in Iran. Female and ilitrate elders were sufering of more disability. These findings indicated the nessesity to more attention to these voulnarable subgroups of population.

  1. Gut transfer factors

    International Nuclear Information System (INIS)

    1990-01-01

    A Nuclear Energy Agency (NEA) Expert Group has proposed values for the absorbed fractions (f 1 values) of radionuclides ingested in food and drinking water by members of the public. The f 1 values for adults, which are also taken to apply to children from 1 year of age, are increased from those given in ICRP Publication 30 for occupationally exposed adults for 7 elements out of the 31 considered. Since the publication of the NEA report, further information has become available that is relevant to the choice of f 1 values for polonium and thorium. These data suggest that for the present the f 1 value for polonium currently recommended by ICRP (0.1) should be retained, and that for thorium a reasonable f 1 value is 0.0005. With these exceptions, the NRPB endorses the revisions in f 1 values proposed by the NEA Expert Group for adults and children from 1 year of age. Higher f 1 values are proposed by the NEA expert Group for absorption in the first year of life. For adult values of between 0.01 and 0.5, an increase by a factor of two is assumed, and for adult values of 0.001 or less, absorption by infants is taken to be ten times greater. This approach is consistent with, and extends, that applied to the actinides in ICRP Publication 48 and represents a reasonable interpretation of current evidence. The NRPB therefore endorses the approach proposed by the NEA Expert Group for the calculation of doses to infants. (author)

  2. Factors Affecting Medical Service Quality.

    Science.gov (United States)

    Mosadeghrad, Ali Mohammad

    2014-02-01

    A better understanding of factors influencing quality of medical service can pinpoint better strategies for quality assurance in medical services. This study aimed to identify factors affecting the quality of medical services provided by Iranian physicians. Exploratory in-depth individual interviews were conducted with sixty-four physicians working in various medical institutions in Iran. Individual, organizational and environmental factors enhance or inhibit the quality of medical services. Quality of medical services depends on the personal factors of the physician and patient, and factors pertaining to the healthcare setting and the broader environment. Differences in internal and external factors such as availability of resources, patient cooperation and collaboration among providers affect the quality of medical services and patient outcomes. Supportive leadership, proper planning, education and training and effective management of resources and processes improve the quality of medical services. This article contributes to healthcare theory and practice by developing a conceptual framework for understanding factors that influence medical services quality.

  3. Prognostic factors of breast cancer

    International Nuclear Information System (INIS)

    Gonzalez Ortega, Jose Maria; Morales Wong, Mario Miguel; Lopez Cuevas, Zoraida; Diaz Valdez, Marilin

    2011-01-01

    The prognostic factors must to be differentiated of the predictive ones. A prognostic factor is any measurement used at moment of the surgery correlated with the free interval of disease or global survival in the absence of the systemic adjuvant treatment and as result is able to correlate with the natural history of the disease. In contrast, a predictive factor is any measurement associated with the response to a given treatment. Among the prognostic factors of the breast cancer are included the clinical, histological, biological, genetic and psychosocial factors. In present review of psychosocial prognostic factors has been demonstrated that the stress and the depression are negative prognostic factors in patients presenting with breast cancer. It is essential to remember that the assessment of just one prognostic parameter is a help but it is not useful to clinical and therapeutic management of the patient.(author)

  4. The population factor.

    Science.gov (United States)

    Kats, G

    1983-01-01

    Reducing population growth is essentil to Egypt's broader efforts to improve facilities, services, and the phsycial quality of life. Although a family planning program has existed since the mid-1950s, the 2.7% annual rate of population growth has not changed in 30 years. Nasser and the other "free officers" who seized power in 1952 became concerned about the adverse effects of the rapidly growing population, but perhaps out of concern with a possible religious backlash, they confined themselves to launching studies and subsidizing several dozen private family planning clinics. From 1962-72, the number of private clinics grew from 28 to 480, and family planning was introduced in government healthclinics in 1965. Such clinics are mainly located in rural areas and are staffed by doctors and other personnel who are not members of the local community and are not very effective at promoting family planning. Local girls and women called Rayadet were recruited to promote the idea to birth control in local communities. By 1970, 12.6% of Egyptians were using reliable contraception. A national survey 12 years later found 34% using contraception, buth the figure seems high. Approximately 60-65% of eligible couples would need to practice birth control for Egypt to reach a less than 1% annuel increase. The Egyptian government hopes to slow population growth to 1% by the year 2000, but major problems of motivation remain especially among the rural poor. Several factors may lead to success of the family planning effort: 1) financial and technical support from international family planning sources has grown rapidley and is likely to remain high; 2) the mortality rate has dropped from 17.8/1000 in 1952 to about half that level, while the rate of natural increase is about the same, suggesting that future reductions in the birth rate will translate to a reduced rate of natural increase, and that parents will be less reluctant to practice faimly planning if there is a greater chance

  5. A factor analysis to detect factors influencing building national brand

    Directory of Open Access Journals (Sweden)

    Naser Azad

    Full Text Available Developing a national brand is one of the most important issues for development of a brand. In this study, we present factor analysis to detect the most important factors in building a national brand. The proposed study uses factor analysis to extract the most influencing factors and the sample size has been chosen from two major auto makers in Iran called Iran Khodro and Saipa. The questionnaire was designed in Likert scale and distributed among 235 experts. Cronbach alpha is calculated as 84%, which is well above the minimum desirable limit of 0.70. The implementation of factor analysis provides six factors including “cultural image of customers”, “exciting characteristics”, “competitive pricing strategies”, “perception image” and “previous perceptions”.

  6. Risk factors for stress fractures.

    Science.gov (United States)

    Bennell, K; Matheson, G; Meeuwisse, W; Brukner, P

    1999-08-01

    Preventing stress fractures requires knowledge of the risk factors that predispose to this injury. The aetiology of stress fractures is multifactorial, but methodological limitations and expediency often lead to research study designs that evaluate individual risk factors. Intrinsic risk factors include mechanical factors such as bone density, skeletal alignment and body size and composition, physiological factors such as bone turnover rate, flexibility, and muscular strength and endurance, as well as hormonal and nutritional factors. Extrinsic risk factors include mechanical factors such as surface, footwear and external loading as well as physical training parameters. Psychological traits may also play a role in increasing stress fracture risk. Equally important to these types of analyses of individual risk factors is the integration of information to produce a composite picture of risk. The purpose of this paper is to critically appraise the existing literature by evaluating study design and quality, in order to provide a current synopsis of the known scientific information related to stress fracture risk factors. The literature is not fully complete with well conducted studies on this topic, but a great deal of information has accumulated over the past 20 years. Although stress fractures result from repeated loading, the exact contribution of training factors (volume, intensity, surface) has not been clearly established. From what we do know, menstrual disturbances, caloric restriction, lower bone density, muscle weakness and leg length differences are risk factors for stress fracture. Other time-honoured risk factors such as lower extremity alignment have not been shown to be causative even though anecdotal evidence indicates they are likely to play an important role in stress fracture pathogenesis.

  7. [Predictive factors of anxiety disorders].

    Science.gov (United States)

    Domschke, K

    2014-10-01

    Anxiety disorders are among the most frequent mental disorders in Europe (12-month prevalence 14%) and impose a high socioeconomic burden. The pathogenesis of anxiety disorders is complex with an interaction of biological, environmental and psychosocial factors contributing to the overall disease risk (diathesis-stress model). In this article, risk factors for anxiety disorders will be presented on several levels, e.g. genetic factors, environmental factors, gene-environment interactions, epigenetic mechanisms, neuronal networks ("brain fear circuit"), psychophysiological factors (e.g. startle response and CO2 sensitivity) and dimensional/subclinical phenotypes of anxiety (e.g. anxiety sensitivity and behavioral inhibition), and critically discussed regarding their potential predictive value. The identification of factors predictive of anxiety disorders will possibly allow for effective preventive measures or early treatment interventions, respectively, and reduce the individual patient's suffering as well as the overall socioeconomic burden of anxiety disorders.

  8. Factor of originality in advertising

    OpenAIRE

    Ešner, Rudolf

    2009-01-01

    The bachelor thesis deals with exploitation of original attitudes in advertising. The thesis solves answers, what role plays the factor of originality in advertising, when and why firms use that factor, how creators work with it, how consumers perceive the factor and what other elements it generally contains. The bachelor thesis qualifies relationship of advertising and originality, describes and probes practical situations, when originality in advertising can be used as a serious competitive...

  9. Risk factors in school shootings.

    Science.gov (United States)

    Verlinden, S; Hersen, M; Thomas, J

    2000-01-01

    Nine incidents of multiple-victim homicide in American secondary schools are examined and common risk factors are identified. The literature dealing with individual, family, social, societal, and situational risk factors for youth violence and aggression is reviewed along with existing risk assessment methods. Checklists of risk factors for serious youth violence and school violence are used in reviewing each school shooting case. Commonalties among the cases and implications for psychologists practicing in clinical and school settings are discussed.

  10. First course in factor analysis

    CERN Document Server

    Comrey, Andrew L

    2013-01-01

    The goal of this book is to foster a basic understanding of factor analytic techniques so that readers can use them in their own research and critically evaluate their use by other researchers. Both the underlying theory and correct application are emphasized. The theory is presented through the mathematical basis of the most common factor analytic models and several methods used in factor analysis. On the application side, considerable attention is given to the extraction problem, the rotation problem, and the interpretation of factor analytic results. Hence, readers are given a background of

  11. Summable series and convergence factors

    CERN Document Server

    Moore, Charles N

    1938-01-01

    Fairly early in the development of the theory of summability of divergent series, the concept of convergence factors was recognized as of fundamental importance in the subject. One of the pioneers in this field was C. N. Moore, the author of the book under review.... Moore classifies convergence factors into two types. In type I he places the factors which have only the property that they preserve convergence for a convergent series or produce convergence for a summable series. In type II he places the factors which not only maintain or produce convergence but have the additional property that

  12. Gene regulation by growth factors

    International Nuclear Information System (INIS)

    Metz, R.; Gorham, J.; Siegfried, Z.; Leonard, D.; Gizang-Ginsberg, E.; Thompson, M.A.; Lawe, D.; Kouzarides, T.; Vosatka, R.; MacGregor, D.; Jamal, S.; Greenberg, M.E.; Ziff, E.B.

    1988-01-01

    To coordinate the proliferation and differentiation of diverse cell types, cells of higher eukaryotes communicate through the release of growth factors. These peptides interact with specific transmembrane receptors of other cells and thereby generate intracellular messengers. The many changes in cellular physiology and activity that can be induced by growth factors imply that growth factor-induced signals can reach the nucleus and control gene activity. Moreover, current evidence also suggests that unregulated signaling along such pathways can induce aberrant proliferation and the formation of tumors. This paper reviews investigations of growth factor regulation of gene expression conducted by the authors' laboratory

  13. Factorization method of quadratic template

    Science.gov (United States)

    Kotyrba, Martin

    2017-07-01

    Multiplication of two numbers is a one-way function in mathematics. Any attempt to distribute the outcome to its roots is called factorization. There are many methods such as Fermat's factorization, Dixońs method or quadratic sieve and GNFS, which use sophisticated techniques fast factorization. All the above methods use the same basic formula differing only in its use. This article discusses a newly designed factorization method. Effective implementation of this method in programs is not important, it only represents and clearly defines its properties.

  14. Social networks and factor markets

    DEFF Research Database (Denmark)

    Abay, Kibrom Araya; Kahsay, Goytom Abraha; Berhane, Guush

    In the absence of well-established factor markets, the role of indigenous institutions and social networks can be substantial for mobilizing factors for agricultural production. We investigate the role of an indigenous social network in Ethiopia, the iddir, in facilitating factor market...... transactions among smallholder farmers. Using detailed longitudinal household survey data and employing a difference-in-differences approach, we find that iddir membership improves households’ access to factor markets. Specifically, we find that joining an iddir network improves households’ access to land...

  15. How a Mutation that Slows Aging Can Also Disproportionately Extend End-of-Life Decrepitude

    Directory of Open Access Journals (Sweden)

    Katie Podshivalova

    2017-04-01

    Full Text Available Summary: The goal of aging research is to extend healthy, active life. For decades, C. elegans daf-2 insulin/insulin-like growth factor 1 (IGF-1 receptor mutants have served as a model for extended lifespan and youthfulness. However, a recent report suggested that their longevity is associated with an undesirable phenotype: a disproportionately long period of decrepitude at the end of life. In the human population, such an outcome would be a burden to society, bringing into question the relevance of daf-2 mutants as a model for life extension. However, here we report that, following an extended period of movement, daf-2 mutants survive longer in a decrepit state because of a beneficial trait: they are resistant to colonization of the digestive tract by dietary bacteria, a condition that leads to premature death in the wild-type and prevents their manifestation of decrepitude. If bacterial colonization is prevented, then daf-2 mutants lead both chronologically and proportionately healthier lives relative to the wild-type. : Podshivalova et al. show that long-lived C. elegans insulin/IGF-1 receptor mutants remain active longer but then resist bacterially induced mortality, allowing them to survive into a state of end-of-life decrepitude. Thus, changes that slow aging and also prevent an age-associated catastrophe can extend both the youthful and infirm periods of life. Keywords: aging, lifespan, healthspan, daf-2, mortality, IGF-1, pathogenesis

  16. Disruption of insulin signalling preserves bioenergetic competence of mitochondria in ageing Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Vanfleteren Jacques R

    2010-06-01

    Full Text Available Abstract Background The gene daf-2 encodes the single insulin/insulin growth factor-1-like receptor of Caenorhabditis elegans. The reduction-of-function allele e1370 induces several metabolic alterations and doubles lifespan. Results We found that the e1370 mutation alters aerobic energy production substantially. In wild-type worms the abundance of key mitochondrial proteins declines with age, accompanied by a dramatic decrease in energy production, although the mitochondrial mass, inferred from the mitochondrial DNA copy number, remains unaltered. In contrast, the age-dependent decrease of both key mitochondrial proteins and bioenergetic competence is considerably attenuated in daf-2(e1370 adult animals. The increase in daf-2(e1370 mitochondrial competence is associated with a higher membrane potential and increased reactive oxygen species production, but with little damage to mitochondrial protein or DNA. Together these results point to a higher energetic efficiency of daf-2(e1370 animals. Conclusions We conclude that low daf-2 function alters the overall rate of ageing by a yet unidentified mechanism with an indirect protective effect on mitochondrial function.

  17. Mechanisms of evasion of Schistosoma mansoni schistosomula to the lethal activity of complement

    Directory of Open Access Journals (Sweden)

    F. Juarez Ramalho-Pinto

    1992-01-01

    Full Text Available Schistosomula of Schistosoma mansoni became resistant to antibody-dependent complement damage in vitro after pre-incubation with normal human erythrocytes (NHuE whatever the ABO or Rh blood group. Resistant parasites were shown to acquire host decay accelerating factor (DAF , a 70 kDa glycoprotein attached to the membrane of NHue by a GPI anchor. IgG2a mAb anti-human DAF (IA10 immunoprecipitated a 70 kDa molecule from 125I-labeled schistosomula pre-incubated with NHuE and inhibited their resistance to complement-dependent killing in vtro. Incubationof schistosomula with erytrocytes from patients with paroxsimal nocturnal hemoglobinuria (PNHE or SRBC, wich are DAF-deficient, did not protect the parasites from complement lesion. Supernatant of 100,000 x g collected from NHuE incubated for 24 h in defined medium was shown to contain a soluble form of DAF and to protect schistosomula from complement killing. Schistosomula treated with trypsin before incubation with NHuE ghosts did not become resistant to complement damage. On the other hand, pre-treatment with chymotrypsin did not interfere with the acquisition of resistance by the schistosomula. These results indicate that, in vitro, NHuE DAF can be transferred to schistosomula in a soluble form and that the binding of this molecule to the parasite surface is dependent upon trypsin-sensitive chymotrypsin-insensitive polipeptide(s present on the surface of the worm.

  18. FACTORING- CREDIT OPPORTUNITIES IN ROMANIA

    Directory of Open Access Journals (Sweden)

    ADELA IONESCU

    2013-05-01

    Full Text Available Capital is the main factor of production, business development becomes virtually impossible without taking into account the financial market and the resources it provides to businesses. Any business, regardless of its degree of development, is involving direct contact with financial markets, namely the institutions that mediate mobilization of capital and the services they provide. Understanding the functioning of the financial system, the specific financial mechanisms through which savings are allocated to support capital investments and the costs and risks involved is essential for the development of a solid base for business. In this context, factoring operations can support economic agents, allowing a transfer of commercial receivables from their holder to a factor who commits to their recovery and guarantee such operations even if temporary or permanent insolvency of the debtor . Thus, factoring is a complex technique in at least two aspects, of the debt and the transfer of credit. . Factoring is a means of financing business, especially export-import transactions, less known in Romania. Maybe because of poor business environment popularize the term is as little known as it was a few years ago the leasing. Present in Romanian legislation since 2002, factoring appears as a contract between one party (called adherent, providing goods or service and a banking company or a financial institution specialized (called factor, which the last one shall finance debts pursuing and preservation against credit risks and adherent gives factor by way of sale, debts arising from the sale of goods or services to third parties. The article is divided into three parts. In the first part we defined the concept of factoring and international factoring, then I presented the advantages and development of factoring in Romania, and the last part conclusions.

  19. MIVIS image geocoding experience on merging position attitude system data and public domain GPS stream (ASI-GeoDAF

    Directory of Open Access Journals (Sweden)

    S. Pignatti

    2006-06-01

    Full Text Available The use of airborne scanners involves geo-referencing problems, which are difficult because of the need to know the exact platform position and attitude for each scan line. The errors of the onboard navigation system are normally corrected using ground control point on the image. This post-processing correction procedure is too long in case of multiple flight campaigns, and besides it implies the need to have available 1:10000 orthophotoimages or maps in digital format. To optimize the above procedure a new method to correct MIVIS navigational data in the post-processing phase has been implemented. The procedure takes into consideration the GPS stream in Rinex format of common knowledge and findable on the web, acquired at the ground stations of the Geodetic Data Archiving Facilities provided by ASI. The application of this correction entails the assumption that the environmental variables affecting both onboard and geodetic GPS equally affect the position measurements. The airborne data correction was carried out merging the two data sets (onboard and ground station GPS to achieve a more precise aircraft trajectory. The present study compares the geo-coded images obtained by means of the two post-processing methods.

  20. Towards Greater Individualization and Process-Oriented Learning through Electronic Self-Access: Project "e-daf"

    Science.gov (United States)

    Chan, Wai Meng; Kim, Dong-Ha

    2004-01-01

    Research in cognitive psychology and second language learning has underlined the significance of learners' cognitive processes and individual preferences in language learning. Helping learners to be aware of these processes and preferences has in fact become an important methodological principle of language teaching. Advances in information and…

  1. Characterization of self-organized InGaN/GaN quantum dots by Diffraction Anomalous Fine Structure (DAFS)

    International Nuclear Information System (INIS)

    Piskorska, E.; Holy, V.; Siebert, M.; Schmidt, Th.; Falta, J.; Yamaguchi, T.; Hommel, D.; Renevier, H.

    2006-01-01

    The local chemical composition of InGaN quantum dots grown by a MBE method on GaN virtual substrates was investigated by x-ray diffraction anomalous fine-structure method. From the detailed numerical analysis of the data we were able to reconstruct the local neighborhood of Ga atoms at different positions in the dots. Using this approach, we found that the In content increases from 20% at the dot base to 40-50% at the top. (author) [pl

  2. PHILOSOPHIE(GESCHICHTE AUF GRUNDLAGE VON GAARDERS «SOFIES WELT» IM DAF-SACHUNTERRICHT NACH LDL

    Directory of Open Access Journals (Sweden)

    Guido Oebel

    2011-11-01

    Full Text Available : Thoroughly positive experience previously gained from both philosophical and issues of philosophical history in social study classes (cf. Hengelbrock 1991a; b; c; 1992; Heller 1994 convinced the author to even go beyond that by implementing Jostein Gaarder’s project idea “Sophie’s World” in a kind of special classroom of German as foreign language (cf. Oebel 2005a; b; c; 2007. In this context, Jean-Pol Martin’s “holistic approach” (Abendroth-Timmer LdL (“Learning-by-Teaching” for German “Lernen-durch-Lehren” seems to be the probably most emphatic constructivistic project teaching method (cf. Scheelhaas 1997; 2003; Wolff 2002, a fact that it has already proved impressively and sustainably not only in the follow-up project presently described but on several other occasions.

  3. FOXO/DAF-16 Activation Slows Down Turnover of the Majority of Proteins in C. elegans

    Energy Technology Data Exchange (ETDEWEB)

    Dhondt, Ineke; Petyuk, Vladislav A.; Cai, Huaihan; Vandemeulebroucke, Lieselot; Vierstraete, Andy; Smith, Richard D.; Depuydt, Geert; Braeckman, Bart P.

    2016-09-01

    Cellular protein quality can be maintained by proteolytic elimination of damaged proteins and replacing them with newly synthesized copies, a process called protein turnover (Ward, 2000). Protein turnover rates have been estimated using SILAC (stable isotope labeling by amino acids in cell culture) in prokaryotes and eukaryotes. The last decade has witnessed a growing interest in the analysis of whole-organism proteome dynamics in metazoans using the same approach (Claydon and Beynon, 2012). In recent work, SILAC was applied to monitor protein synthesis throughout life in adult Caenorhabditis elegans (Vukoti et al., 2015) and to investigate food intake (Gomez-Amaro et al., 2015

  4. MicroRNA mir-34 provides robustness to environmental stress response via the DAF-16 network in C. elegans

    NARCIS (Netherlands)

    Isik, Meltem; Blackwell, T. Keith; Berezikov, Eugene

    2016-01-01

    Diverse stresses and aging alter expression levels of microRNAs, suggesting a role for these posttranscriptional regulators of gene expression in stress modulation and longevity. Earlier studies demonstrated a central role for the miR-34 family in promoting cell cycle arrest and cell death following

  5. Activation of factor VII bound to tissue factor: a key early step in the tissue factor pathway of blood coagulation.

    OpenAIRE

    Rao, L V; Rapaport, S I

    1988-01-01

    Whether the factor VII/tissue factor complex that forms in tissue factor-dependent blood coagulation must be activated to factor VIIa/tissue factor before it can activate its substrates, factor X and factor IX, has been a difficult question to answer because the substrates, once activated, back-activate factor VII. Our earlier studies suggested that human factor VII/tissue factor cannot activate factor IX. Studies have now been extended to the activation of factor X. Reaction mixtures were ma...

  6. Activation of factor VII bound to tissue factor: A key early step in the tissue factor pathway of blood coagulation

    International Nuclear Information System (INIS)

    Rao, L.V.M.; Rapaport, S.I.

    1988-01-01

    Whether the factor VII/tissue factor complex that forms in tissue factor-dependent blood coagulation must be activated to factor VIIa/tissue factor before it can activate its substrates, factor X and IX, has been a difficult question to answer because the substrates, once activated, back-activate factor VII. The earlier studies suggested that human factor VII/tissue factor cannot activate factor IX. Studies have now been extended to the activation of factor X. Reaction mixtures were made with purified factor VII, X, and tissue factor; in some experiments antithrombin III and heparin were added to prevent back-activation of factor VII. Factor X was activated at similar rates in reaction mixtures containing either VII or factor VIIa after an initial 30-sec lag with factor VII. In reaction mixtures with factor VII a linear activation of factor X was established several minutes before cleavage of 125 I-labeled factor VII to the two-chain activated molecule was demonstrable on gel profiles. These data suggest that factor VII/tissue factor cannot activate measurable amounts of factor X over several minutes. Overall, the results support the hypothesis that a rapid preferential activation of factor VII bound to tissue factor by trace amounts of factor Xa is a key early step in tissue factor-dependent blood coagulation

  7. Factors of trade in Europe

    Czech Academy of Sciences Publication Activity Database

    Hanousek, Jan; Kočenda, Evžen

    2014-01-01

    Roč. 38, č. 4 (2014), s. 518-535 ISSN 0939-3625 R&D Projects: GA ČR(CZ) GAP403/12/0080 Grant - others:UK(CZ) UNCE 204005/2012 Institutional support: PRVOUK-P23 Keywords : bilateral trade * factors of trade * panel data Subject RIV: AH - Economics Impact factor: 0.649, year: 2014

  8. Quadratic prediction of factor scores

    NARCIS (Netherlands)

    Wansbeek, T

    1999-01-01

    Factor scores are naturally predicted by means of their conditional expectation given the indicators y. Under normality this expectation is linear in y but in general it is an unknown function of y. II is discussed that under nonnormality factor scores can be more precisely predicted by a quadratic

  9. Hidden Risk Factors for Women

    Science.gov (United States)

    ... A.S.T. Quiz Hidden Stroke Risk Factors for Women Updated:Nov 22,2016 Excerpted from "What Women Need To Know About The Hidden Risk Factors ... 2012) This year, more than 100,000 U.S. women under 65 will have a stroke. Stroke is ...

  10. Factor analysis of multivariate data

    Digital Repository Service at National Institute of Oceanography (India)

    Fernandes, A.A.; Mahadevan, R.

    A brief introduction to factor analysis is presented. A FORTRAN program, which can perform the Q-mode and R-mode factor analysis and the singular value decomposition of a given data matrix is presented in Appendix B. This computer program, uses...

  11. Pineal factors other than melatonin

    NARCIS (Netherlands)

    Ebels, I.

    Some sheep pineal factors other than melatonin are described. A “nonmelatonin” antigonadotropic activity has been detected by application of the inhibition of compensatory ovarian hypertrophy (COH) in unilaterally ovariectomized adult Charles River CD-1 mice. The factor has been extracted from

  12. Stroke Risk Factors and Symptoms

    Science.gov (United States)

    ... » [ pdf, 433 kb ] Order Materials » Stroke Risk Factors and Symptoms Risk Factors for a Stroke Stroke prevention is still ... it. Treatment can delay complications that increase the risk of stroke. Transient ischemic attacks (TIAs). Seek help. ...

  13. Electromagnetic form factors of hadrons

    International Nuclear Information System (INIS)

    Zidell, V.S.

    1976-01-01

    A vector meson dominance model of the electromagnetic form factors of hadrons is developed which is based on the use of unstable particle propagators. Least-square fits are made to the proton, neutron, pion and kaon form factor data in both the space and time-like regions. A good fit to the low-energy nucleon form factor data is obtained using only rho, ω, and phi dominance, and leads to a determination of the vector meson resonance parameters in good agreement with experiment. The nucleon-vector meson coupling constants obey simple sum rules indicating that there exists no hard core contribution to the form factors within theoretical uncertainties. The prediction for the electromagnetic radii of the proton is in reasonable agreement with recent experiments. The pion and kaon charge form factors as deduced from the nucleon form factors assuming vector meson universality are compared to the data. The pion form factor agrees with the data in both the space and time-like regions. The pion charge radius is in agreement with the recent Dubna result, but the isovector P-wave pion-pion phase shift calculated from the theory disagrees with experiment. A possible contribution to the form factors from a heavy rho meson is also evaluated

  14. Shell model and spectroscopic factors

    International Nuclear Information System (INIS)

    Poves, P.

    2007-01-01

    In these lectures, I introduce the notion of spectroscopic factor in the shell model context. A brief review is given of the present status of the large scale applications of the Interacting Shell Model. The spectroscopic factors and the spectroscopic strength are discussed for nuclei in the vicinity of magic closures and for deformed nuclei. (author)

  15. EAMJ Risk Factors 10.indd

    African Journals Online (AJOL)

    2010-02-02

    Feb 2, 2010 ... Several factors have been suggested as independent risk factors for their development. Identification of these ... with age, gender or haematological test. ... A meta-analysis of prospective studies on ..... The marked difference may be because monthly .... and dyslipidemia among patients taking first-line,.

  16. Factors That Shape Design Thinking

    Science.gov (United States)

    Gray, Colin M.

    2013-01-01

    A wide range of design literature discusses the role of the studio and its related pedagogy in the development of design thinking. Scholars in a variety of design disciplines pose a number of factors that potentially affect this development process, but a full understanding of these factors as experienced from a critical pedagogy or student…

  17. Kadison-Kastler stable factors

    DEFF Research Database (Denmark)

    Cameron, Jan; Christensen, Erik; Sinclair, Allan M.

    2014-01-01

    It is proven that a pair of continuous finite von Neumann algebra factors are unitarily equivalent if sufficiently close and one satisfies a certain cohomological condition.......It is proven that a pair of continuous finite von Neumann algebra factors are unitarily equivalent if sufficiently close and one satisfies a certain cohomological condition....

  18. Human factors influencing decision making

    OpenAIRE

    Jacobs, Patricia A.

    1998-01-01

    This report supplies references and comments on literature that identifies human factors influencing decision making, particularly military decision making. The literature has been classified as follows (the classes are not mutually exclusive): features of human information processing; decision making models which are not mathematical models but rather are descriptive; non- personality factors influencing decision making; national characteristics influencing decision makin...

  19. Factoring in Factor VIII With Acute Ischemic Stroke.

    Science.gov (United States)

    Siegler, James E; Samai, Alyana; Albright, Karen C; Boehme, Amelia K; Martin-Schild, Sheryl

    2015-10-01

    There is growing research interest into the etiologies of cryptogenic stroke, in particular as it relates to hypercoagulable states. An elevation in serum levels of the procoagulant factor VIII is recognized as one such culprit of occult cerebral infarctions. It is the objective of the present review to summarize the molecular role of factor VIII in thrombogenesis and its clinical use in the diagnosis and prognosis of acute ischemic stroke. We also discuss the utility of screening for serum factor VIII levels among patients at risk for, or those who have experienced, ischemic stroke. © The Author(s) 2015.

  20. Using Bayes factors for multi-factor, biometric authentication

    Science.gov (United States)

    Giffin, A.; Skufca, J. D.; Lao, P. A.

    2015-01-01

    Multi-factor/multi-modal authentication systems are becoming the de facto industry standard. Traditional methods typically use rates that are point estimates and lack a good measure of uncertainty. Additionally, multiple factors are typically fused together in an ad hoc manner. To be consistent, as well as to establish and make proper use of uncertainties, we use a Bayesian method that will update our estimates and uncertainties as new information presents itself. Our algorithm compares competing classes (such as genuine vs. imposter) using Bayes Factors (BF). The importance of this approach is that we not only accept or reject one model (class), but compare it to others to make a decision. We show using a Receiver Operating Characteristic (ROC) curve that using BF for determining class will always perform at least as well as the traditional combining of factors, such as a voting algorithm. As the uncertainty decreases, the BF result continues to exceed the traditional methods result.

  1. What factors influence mitigative capacity?

    International Nuclear Information System (INIS)

    Winkler, Harald; Baumert, Kevin; Blanchard, Odile; Burch, Sarah; Robinson, John

    2007-01-01

    This article builds on Yohe's seminal piece on mitigative capacity, which elaborates 'determinants' of mitigative capacity, also reflected in the IPCC's third assessment report. We propose a revised definition, where mitigative capacity is a country's ability to reduce anthropogenic greenhouse gas emissions or enhance natural sinks. By 'ability' we mean skills, competencies, fitness, and proficiencies that a country has attained which can contribute to GHG emissions mitigation. A conceptual framework is proposed, linking mitigative capacity to a country's sustainable development path, and grouping the factors influencing mitigative capacity into three main sets: economic factors, institutional ones, and technology. Both quantitative and qualitative analysis of factors is presented, showing how these factors vary across countries. We suggest that it is the interplay between the three economic factors-income, abatement cost and opportunity cost-that shape mitigative capacity. We find that income is an important economic factor influencing mitigative capacity, while abatement cost is important in turning mitigative capacity into actual mitigation. Technology is a critical mitigative capacity, including the ability to absorb existing climate-friendly technologies or to develop innovative ones. Institutional factors that promote mitigative capacity include the effectiveness of government regulation, clear market rules, a skilled work force and public awareness. We briefly investigate such as high abatement cost or lack of political willingness that prevent mitigative capacity from being translated into mitigation

  2. Corrosion effects on friction factors

    International Nuclear Information System (INIS)

    Magleby, H.L.; Shaffer, S.J.

    1996-01-01

    This paper presents the results of NRC-sponsored material specimen tests that were performed to determine if corrosion increases the friction factors of sliding surfaces of motor-operated gate valves, which could require higher forces to close and open safety-related valves when subjected to their design basis differential pressures. Friction tests were performed with uncorroded specimens and specimens subjected to accelerated corrosion. Preliminary tests at ambient conditions showed that corrosion increased the friction factors, indicating the need for additional tests duplicating valve operating parameters at hot conditions. The additional tests showed friction factors of corroded specimens were 0.1 to 0.2 higher than for uncorroded specimens, and that the friction factors of the corroded specimens were not very dependent on contact stress or corrosion film thickness. The measured values of friction factors for the three corrosion films tested (simulating three operating times) were in the range of 0.3 to 0.4. The friction factor for even the shortest simulated operating time was essentially the same as the others, indicating that the friction factors appear to reach a plateau and that the plateau is reached quickly

  3. Conversion factors and oil statistics

    International Nuclear Information System (INIS)

    Karbuz, Sohbet

    2004-01-01

    World oil statistics, in scope and accuracy, are often far from perfect. They can easily lead to misguided conclusions regarding the state of market fundamentals. Without proper attention directed at statistic caveats, the ensuing interpretation of oil market data opens the door to unnecessary volatility, and can distort perception of market fundamentals. Among the numerous caveats associated with the compilation of oil statistics, conversion factors, used to produce aggregated data, play a significant role. Interestingly enough, little attention is paid to conversion factors, i.e. to the relation between different units of measurement for oil. Additionally, the underlying information regarding the choice of a specific factor when trying to produce measurements of aggregated data remains scant. The aim of this paper is to shed some light on the impact of conversion factors for two commonly encountered issues, mass to volume equivalencies (barrels to tonnes) and for broad energy measures encountered in world oil statistics. This paper will seek to demonstrate how inappropriate and misused conversion factors can yield wildly varying results and ultimately distort oil statistics. Examples will show that while discrepancies in commonly used conversion factors may seem trivial, their impact on the assessment of a world oil balance is far from negligible. A unified and harmonised convention for conversion factors is necessary to achieve accurate comparisons and aggregate oil statistics for the benefit of both end-users and policy makers

  4. Factors Influencing of Social Conflict

    Directory of Open Access Journals (Sweden)

    Suwandi Sumartias

    2013-07-01

    Full Text Available Social conflicts that occur in several areas in Indonesia lately, one of them is caused by the weakness of law certainty. This is feared to threaten the integration of the Republic of Indonesia. This study aims to determine the factors that affect social conflict in Manis Lor village in Kuningan district. The method used the explanatory quantitative methods, the statistical test Path Analysis. The study population was a formal and informal community leaders (village chief, clergy, and youth, and the people who involved in a conflict in Manis Lor village Kuningan regency. The result shows a There is no significant influence between social identity factors with social conflict anarchist. b There is significant influence between socio-economic factors with social conflict anarchists. c There is no significant influence between the credibility factor anarchist leaders with social conflict. d There is no significant influence between the motive factor with anarchist social conflict. e There is significant influence between personality factors/beliefs with anarchist social conflict. f There is significant influence of behavioral factors anarchist communication with social conflict.

  5. Factor concentrates for the treatment of factor XIII deficiency.

    Science.gov (United States)

    Gootenberg, J E

    1998-11-01

    Factor XIII deficiency is a severe autosomal recessive bleeding disorder associated with a characteristic pattern of neonatal hemorrhage and a lifelong bleeding diathesis. Even relatively minor trauma can be followed by prolonged and recurrent bleeding. Intracranial hemorrhage is a frequent complication. With the development of safe and effective factor XIII concentrates, reliable prophylactic treatment is possible. Two plasma-derived, virus-inactivated factor XIII concentrates are currently in production. The first, Fibrogammin P, (Centeon LLC, King of Prussia, PA, USA; and Centeon Pharma GmbH, Marburg, Germany) is marketed in Europe, South America, South Africa, and Japan. It is distributed in the United States under a Food and Drug Administration Investigational New Drug Application. A second factor XIII concentrate (Bio Products Laboratory, Elstree, UK) is available for use only on a "named patient" compassionate basis in the United Kingdom. Patients with factor XIII deficiency who receive appropriately timed periodic infusions of such factor XIII concentrates are able to live normal lives, free from catastrophic bleeding episodes.

  6. Sequence Factorization with Multiple References.

    Directory of Open Access Journals (Sweden)

    Sebastian Wandelt

    Full Text Available The success of high-throughput sequencing has lead to an increasing number of projects which sequence large populations of a species. Storage and analysis of sequence data is a key challenge in these projects, because of the sheer size of the datasets. Compression is one simple technology to deal with this challenge. Referential factorization and compression schemes, which store only the differences between input sequence and a reference sequence, gained lots of interest in this field. Highly-similar sequences, e.g., Human genomes, can be compressed with a compression ratio of 1,000:1 and more, up to two orders of magnitude better than with standard compression techniques. Recently, it was shown that the compression against multiple references from the same species can boost the compression ratio up to 4,000:1. However, a detailed analysis of using multiple references is lacking, e.g., for main memory consumption and optimality. In this paper, we describe one key technique for the referential compression against multiple references: The factorization of sequences. Based on the notion of an optimal factorization, we propose optimization heuristics and identify parameter settings which greatly influence 1 the size of the factorization, 2 the time for factorization, and 3 the required amount of main memory. We evaluate a total of 30 setups with a varying number of references on data from three different species. Our results show a wide range of factorization sizes (optimal to an overhead of up to 300%, factorization speed (0.01 MB/s to more than 600 MB/s, and main memory usage (few dozen MB to dozens of GB. Based on our evaluation, we identify the best configurations for common use cases. Our evaluation shows that multi-reference factorization is much better than single-reference factorization.

  7. Cardiovascular risk factors and dementia.

    Science.gov (United States)

    Fillit, Howard; Nash, David T; Rundek, Tatjana; Zuckerman, Andrea

    2008-06-01

    Dementias, such as Alzheimer's disease (AD) and vascular dementia, are disorders of aging populations and represent a significant economic burden. Evidence is accumulating to suggest that cardiovascular disease (CVD) risk factors may be instrumental in the development of dementia. The goal of this review was to discuss the relationship between specific CVD risk factors and dementia and how current treatment strategies for dementia should focus on reducing CVD risks. We conducted a review of the literature for the simultaneous presence of 2 major topics, cardiovascular risk factors and dementia (eg, AD). Special emphasis was placed on clinical outcome studies examining the effects of treatments of pharmacologically modifiable CVD risk factors on dementia and cognitive impairment. Lifestyle risk factors for CVD, such as obesity, lack of exercise, smoking, and certain psychosocial factors, have been associated with an increased risk of cognitive decline and dementia. Some evidence suggests that effectively managing these factors may prevent cognitive decline/dementia. Randomized, placebo-controlled trials of antihypertensive medications have found that such therapy may reduce the risk of cognitive decline, and limited data suggest a benefit for patients with AD. Some small open-label and randomized clinical trials of statins have observed positive effects on cognitive function; larger studies of statins in patients with AD are ongoing. Although more research is needed, current evidence indicates an association between CVD risk factors--such as hypertension, dyslipidemia, and diabetes mellitus--and cognitive decline/dementia. From a clinical perspective, these data further support the rationale for physicians to provide effective management of CVD risk factors and for patients to be compliant with such recommendations to possibly prevent cognitive decline/dementia.

  8. Improved multivariate polynomial factoring algorithm

    International Nuclear Information System (INIS)

    Wang, P.S.

    1978-01-01

    A new algorithm for factoring multivariate polynomials over the integers based on an algorithm by Wang and Rothschild is described. The new algorithm has improved strategies for dealing with the known problems of the original algorithm, namely, the leading coefficient problem, the bad-zero problem and the occurrence of extraneous factors. It has an algorithm for correctly predetermining leading coefficients of the factors. A new and efficient p-adic algorithm named EEZ is described. Bascially it is a linearly convergent variable-by-variable parallel construction. The improved algorithm is generally faster and requires less store then the original algorithm. Machine examples with comparative timing are included

  9. Quality factors for monoenergetic neutrons

    International Nuclear Information System (INIS)

    Cross, W.G.; Ing, H.

    1984-01-01

    Mean quality factors anti Q(E/sub n/), for the dose resulting from first interactons of monoenergetic neutrons in tissue, have been calculated at energies from thermal to 14.7 MeV. Knowledge of these values, along with kerma factors, allows the calculation of the heavy-particle dose equivalent for any known neutron spectrum in tissue. The partial quality factors for the dose delivered by C, N, and O elastic and inelastic recoils are found to be virtually independent of the scattering angular distributions and are given by simple expressions

  10. Complement inhibitory proteins expression in placentas of thrombophilic women Complement inhibitory proteins expression in placentas of thrombophilic women

    Directory of Open Access Journals (Sweden)

    Przemysław Krzysztof Wirstlein

    2012-10-01

    Full Text Available Factors controlling complement activation appear to exert a protective effect on pregnancy. This is
    particularly important in women with thrombophilia. The aim of this study was to determine the transcript and
    protein levels of complement decay-accelerating factor (DAF and membrane cofactor protein (MCP in the
    placentas of women with acquired and inherited thrombophilia. Also, we assessed immunohistochemistry staining
    of inhibitors of the complement cascade, DAF and MCP proteins, in the placentas of thrombophilic women.
    Placentas were collected from eight women with inherited thrombophilia and ten with acquired thrombophilia.
    The levels of DAF and MCP transcripts were evaluated by qPCR, the protein level was evaluated by Western
    blot. We observed a higher transcript (p < 0.05 and protein (p < 0.001 levels of DAF and MCP in the placentas
    of thrombophilic women than in the control group. DAF and MCP were localized on villous syncytiotrophoblast
    membranes, but the assessment of staining in all groups did not differ. The observed higher expression level of
    proteins that control activation of complement control proteins is only seemingly contradictory to the changes
    observed for example in the antiphospholipid syndrome. However, given the hitherto known biochemical changes
    associated with thrombophilia, a mechanism in which increased expression of DAF and MCP in the placentas is
    an effect of proinflammatory cytokines, which accompanies thrombophilia, is probable.Factors controlling complement activation appear to exert a protective effect on pregnancy. This is
    particularly important in women with thrombophilia. The aim of this study was to determine the transcript and
    protein levels of complement decay-accelerating factor (DAF and membrane cofactor protein (MCP in the
    placentas of women with acquired and inherited thrombophilia. Also, we assessed immunohistochemistry

  11. Nucleocytoplasmic shuttling of transcription factors

    DEFF Research Database (Denmark)

    Cartwright, P; Helin, K

    2000-01-01

    To elicit the transcriptional response following intra- or extracellular stimuli, the signals need to be transmitted to their site of action within the nucleus. The nucleocytoplasmic shuttling of transcription factors is a mechanism mediating this process. The activation and inactivation...... of the transcriptional response is essential for cells to progress through the cell cycle in a normal manner. The involvement of cytoplasmic and nuclear accessory molecules, and the general nuclear membrane transport components, are essential for this process. Although nuclear import and export for different...... transcription factor families are regulated by similar mechanisms, there are several differences that allow for the specific activation of each transcription factor. This review discusses the general import and export pathways found to be common amongst many different transcription factors, and highlights...

  12. Secreted factors as synaptic organizers.

    Science.gov (United States)

    Johnson-Venkatesh, Erin M; Umemori, Hisashi

    2010-07-01

    A critical step in synaptic development is the differentiation of presynaptic and postsynaptic compartments. This complex process is regulated by a variety of secreted factors that serve as synaptic organizers. Specifically, fibroblast growth factors, Wnts, neurotrophic factors and various other intercellular signaling molecules are proposed to regulate presynaptic and/or postsynaptic differentiation. Many of these factors appear to function at both the neuromuscular junction and in the central nervous system, although the specific function of the molecules differs between the two. Here we review secreted molecules that organize the synaptic compartments and discuss how these molecules shape synaptic development, focusing on mammalian in vivo systems. Their critical role in shaping a functional neural circuit is underscored by their possible link to a wide range of neurological and psychiatric disorders both in animal models and by mutations identified in human patients. © The Authors (2010). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  13. Disadvantage factor for anisotropic scattering

    International Nuclear Information System (INIS)

    Saad, E.A.; Abdel Krim, M.S.; EL-Dimerdash, A.A.

    1990-01-01

    The invariant embedding method is used to solve the problem for a two region reactor with anisotropic scattering and to compute the disadvantage factor necessary for calculating some reactor parameters

  14. Calculation of pion form factor

    International Nuclear Information System (INIS)

    Vahedi, N.; Amirarjomand, S.

    1975-09-01

    The pion form factor is calculated using the structure function Wsub(2), which incorporates kinematical constraints, threshold behaviour and scaling. The Bloom-Gilman sum rule is used and only the two leading Regge trajectories are taken into account

  15. EAMJ Factors Aug.indd

    African Journals Online (AJOL)

    2009-08-01

    Aug 1, 2009 ... Objective: To bridge the existing gaps by examining the factors associated with attrition. Design: ... Results: In this cohort study, 1353 women were enrolled at delivery and 1188 (88%) ... wage earners with poor social support.

  16. HIV: Social and Environmental Factors

    Centers for Disease Control (CDC) Podcasts

    Dr. Kevin Fenton, Director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, discusses how social and environmental factors may put African Americans at greater risk for HIV.

  17. Lithuanian Population Aging Factors Analysis

    Directory of Open Access Journals (Sweden)

    Agnė Garlauskaitė

    2015-05-01

    Full Text Available The aim of this article is to identify the factors that determine aging of Lithuania’s population and to assess the influence of these factors. The article shows Lithuanian population aging factors analysis, which consists of two main parts: the first describes the aging of the population and its characteristics in theoretical terms. Second part is dedicated to the assessment of trends that influence the aging population and demographic factors and also to analyse the determinants of the aging of the population of Lithuania. After analysis it is concluded in the article that the decline in the birth rate and increase in the number of emigrants compared to immigrants have the greatest impact on aging of the population, so in order to show the aging of the population, a lot of attention should be paid to management of these demographic processes.

  18. Environmental risk factors and pressures

    International Nuclear Information System (INIS)

    Klinda, J.; Lieskovska, Z.

    1998-01-01

    In this chapter the physical risk factors (as radiation [air contamination, contamination of the environment components and food contamination], radon and its radioactive decay products, radioactive wastes, noise), chemical risk factors [chemical substances, xenobiotics in the food chain the ozone depletion], wastes (waste generation, waste management, municipal waste management, import, export and transit of waste) and natural an technological hazards (water quality deterioration as a result of various accidents and fire risk) in the Slovak Republic in 1997 are reviewed

  19. Factorization-algebraization-path integration

    International Nuclear Information System (INIS)

    Inomata, A.; Wilson, R.

    1986-01-01

    The authors review the method of factorization proposed by Schroedinger of a quantum mechanical second-order linear differential equation into a product of two first-order differential operators, often referred to as ladder operators, as well as the modifications made to Schroedinger's method by Infeld and Hull. They then review the group theoretical treatments proposed by Miller of the Schroedinger-Infeld-Hull factorizations and go on to demonstrate the application of dynamical symmetry to path integral calculations. 30 references

  20. Factors determining UK album success

    OpenAIRE

    Elliott, Caroline; Simmons, Robert

    2011-01-01

    This article uses a recently compiled dataset on the UK album sales to determine which factors contribute to best-selling album sales success. We control for factors including length of time since release, nationality of artist, artist type and album type, testing the increasing returns to information hypothesis. Information on general public online review scores for the albums in the dataset allows for a strong test of the accuracy of online reviews in predicting music sales, as online revie...

  1. Virulence Factors of Streptococcus mutans.

    Science.gov (United States)

    1986-08-01

    763512/715242 Final Report U VIRULENCE FACTORS OF STREPTOCOCCUS MUTANS U Samuel Rosen Department of Oral Biology For the Period April 1, 1983 - June 30...00 FINAL REPORT VIRULENCE FACTORS OF STREPTOCOCCUS MUTANS Sam Rosen, Irving Shklair, E. X. Beck and F. M. Beck Ohio State University Columbus,Oh and...206-212. Johnson CP, Gorss S, Hillman JD (1978). Cariogenic properties of LDH deficient mutants of streptococcus mutans . J Dent Res 57, Special Issue

  2. Power peaking nuclear reliability factors

    International Nuclear Information System (INIS)

    Hassan, H.A.; Pegram, J.W.; Mays, C.W.; Romano, J.J.; Woods, J.J.; Warren, H.D.

    1977-11-01

    The Calculational Nuclear Reliability Factor (CNRF) assigned to the limiting power density calculated in reactor design has been determined. The CNRF is presented as a function of the relative power density of the fuel assembly and its radial local. In addition, the Measurement Nuclear Reliability Factor (MNRF) for the measured peak hot pellet power in the core has been evaluated. This MNRF is also presented as a function of the relative power density and radial local within the fuel assembly

  3. FACTORS INFLUENCING SECOND LANGUAGE ACQUISITION

    Directory of Open Access Journals (Sweden)

    Siti Khasinah

    2014-05-01

    Full Text Available Motivation, attitude, age, intelligence, aptitude, cognitive style, and personality are considered as factors that greatly influence someone in the process of his or her second language acquisition. Experts state that those factors give a more dominant contribution in SLA to learners variedly, depend on who the learners are, their age, how they behave toward the language, their cognitive ability, and also the way they learn.

  4. Clinical Application of Wedge Factor

    International Nuclear Information System (INIS)

    Choi, Dong Rak; Ahn, Yong Chan; Huh, Sueng Jae

    1995-01-01

    Purpose : In general. The wedge factors which are used clinical practices are ignored of dependency on field sizes and depths. In this present, we investigated systematically the depth and field size dependency to determine the absorbed dose more accurately. Methods : The wedge factors for each wedge filter were measured at various depth (depth of Dmax, 5cm, 10cm, and 15cm) and field sizes (5 X 5cm, 10 X 10cm, 15 X 15cm, 20 X 20 cm) by using 4-,6-, and 10-MV X rays. By convention, wedge factors are determined by taking the ratio of the central axis ionization readings when the wedge filter is in place to those of the open field in same field size and measurement depth. In this present work, we determined the wedge factors for 4-, 6-, and 10-MV X rays from Clinac 600C and 2100C linear accelerators (manufactured by Varian Associates, Inc., Palo Alto, CA). To confirm that the wedge was centered., measurements were done with the two possible wedge position and various collimator orientations. Results : The standard deviations of measured values are within 0.3% and the depth dependence of wedge factor is greater for the lower energies. Especially, the variation of wedge factor is no less than 5% for 4- and 6- MV X rays with more than 45 .deg. wedge filter. But there seems to be a small dependence on field size. Conclusion : The results of this study show a dependence on the point of measurement. There also seems to be a small dependence on field size. And so, we should consider the depth and field size dependence in determining the wedge factors. If one wedge factor were to be used for each wedge filter, it seems that the measurement for a 10cm X 10cm field size at a depth of 10cm would be a reasonable choice

  5. Demand, Energy, and Power Factor

    Science.gov (United States)

    1994-08-01

    POWER FACTOR DEFINITION I Basically , power factor (pf) is a measure of how effectively the plant uses the electricity it purchases from the utility. It...not be made available by the plant. U 24 This video is relatively short, less than fifteen-minutes, and covers the basics on demand, block extenders... ratemaking methodology and test period as used in determining the NC-RS rates. Pending final decision by the FERC, the Federal Government would pay a rate as

  6. Study of vibrational modes and specific heat of wurtzite phase of BN

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Daljit, E-mail: daljit.jt@gmail.com; Sinha, M. M. [Department of Physics, SLIET, Longowal (India)

    2016-05-06

    In these days of nanotechnology the materials like BN is of utmost importance as in hexagonal phase it is among hardest materials. The phonon mode study of the materials is most important factor to find structural and thermodynamcal properties. To study the phonons de launey angular force (DAF) constant model is best suited as it involves many particle interactions. Therefore in this presentation we have studied the lattice dynamical properties and specific heat of BN in wurtzite phase using DAF model. The obtained results are in excellent agreement with existing results.

  7. Study of vibrational modes and specific heat of wurtzite phase of BN

    International Nuclear Information System (INIS)

    Singh, Daljit; Sinha, M. M.

    2016-01-01

    In these days of nanotechnology the materials like BN is of utmost importance as in hexagonal phase it is among hardest materials. The phonon mode study of the materials is most important factor to find structural and thermodynamcal properties. To study the phonons de launey angular force (DAF) constant model is best suited as it involves many particle interactions. Therefore in this presentation we have studied the lattice dynamical properties and specific heat of BN in wurtzite phase using DAF model. The obtained results are in excellent agreement with existing results.

  8. Environmental Factors and Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Omer Faruk Tekbas

    2008-10-01

    Full Text Available Epidemiological and clinical observations have led to the hypothesis that the risk of developing cardiovascular diseases is influenced not only by genetic, lifestyle and major risk factors, but also by environmental factors. Environmental factors are considered key determinants of cardiovascular diseases. Although lifestyle choices such as smoking, diet, and exercise are viewed as major environmental influences, the contribution of pollutants and environmental chemicals is less clear. Accumulating evidence suggests that exposure to physically and chemical pollutants could elevate the risk of cardiovascular diseases. Many epidemiological studies report that exposure to physically, biologically and socio-cultural environmental factors are associated with an increase in cardiovascular mortality. Relationships between environmental factors and coronary arter disease, arhythmias, and cardiomyopathies have been reported. Exposures to arsenic, lead, cadmium, pollutant gases, solvents, and pesticides have also been linked to increased incidence of cardiovascular disease. In this paper, I review that relationships between exposure to physically, chemical, biologically and socio-cultural environmental factors and cardiovascular diseases. [TAF Prev Med Bull 2008; 7(5.000: 435-444

  9. Human factors in resuscitation teaching.

    Science.gov (United States)

    Norris, Elizabeth M; Lockey, Andrew S

    2012-04-01

    There is an increasing interest in human factors within the healthcare environment reflecting the understanding of their impact on safety. The aim of this paper is to explore how human factors might be taught on resuscitation courses, and improve course outcomes in terms of improved mortality and morbidity for patients. The delivery of human factors training is important and this review explores the work that has been delivered already and areas for future research and teaching. Medline was searched using MESH terms Resuscitation as a Major concept and Patient or Leadership as core terms. The abstracts were read and 25 full length articles reviewed. Critical incident reporting has shown four recurring problems: lack of organisation at an arrest, lack of equipment, non functioning equipment, and obstructions preventing good care. Of these, the first relates directly to the concept of human factors. Team dynamics for both team membership and leadership, management of stress, conflict and the role of debriefing are highlighted. Possible strategies for teaching them are discussed. Four strategies for improving human factors training are discussed: team dynamics (including team membership and leadership behaviour), the influence of stress, debriefing, and conflict within teams. This review illustrates how human factor training might be integrated further into life support training without jeopardising the core content and lengthening the courses. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. Growth factors and new periodontology

    Directory of Open Access Journals (Sweden)

    Paknejad M

    1999-06-01

    Full Text Available Growth factors are biological mediators that have a key roll in proliferation, chemotaxy and"ndifferentiation by acting on specific receptors on the surface of cells and regulating events in wound"nhealing.They can be considered hormones that are not released in to the blood stream but have one a"nlocal action. Some of these factors can regulate premature change in GO to Gl phase in cell devesion"ncycle and even may stimulate synthesis of DNA in suitable cells, Growth substances, primarily secreted"nby fibroblasts, endothelia! cells, macrophages and platelet, include platelet derived growth factor"n(PDGF, insulin like growth factor (IGF transforming growth factor (TGFa and (3 and bone"nmorphogenetic proteins BMPs that approximately are the most important of them. (BMPs could be"nused to control events during periodontal, craniofacial and implant wound healing through favoring bone"nformation"nAccording toLynch, combination of PGDF and IGF1 would be effective in promoting growth of all the"ncomponents of the periodontium."nThe aim of this study was to characterize growth factor and review the literature to determine the"nmechanism of their function, classification and application in implant and periodontal treatment.

  11. Sexual harassment: identifying risk factors.

    Science.gov (United States)

    O'Hare, E A; O'Donohue, W

    1998-12-01

    A new model of the etiology of sexual harassment, the four-factor model, is presented and compared with several models of sexual harassment including the biological model, the organizational model, the sociocultural model, and the sex role spillover model. A number of risk factors associated with sexually harassing behavior are examined within the framework of the four-factor model of sexual harassment. These include characteristics of the work environment (e.g., sexist attitudes among co-workers, unprofessional work environment, skewed sex ratios in the workplace, knowledge of grievance procedures for sexual harassment incidents) as well as personal characteristics of the subject (e.g., physical attractiveness, job status, sex-role). Subjects were 266 university female faculty, staff, and students who completed the Sexual Experience Questionnaire to assess the experience of sexual harassment and a questionnaire designed to assess the risk factors stated above. Results indicated that the four-factor model is a better predictor of sexual harassment than the alternative models. The risk factors most strongly associated with sexual harassment were an unprofessional environment in the workplace, sexist atmosphere, and lack of knowledge about the organization's formal grievance procedures.

  12. Modifying factors for metabolic parameters

    International Nuclear Information System (INIS)

    Inaba, Jiro

    1990-01-01

    Studies on factors which influence the metabolic parameter for calculation of radiation doses from intakes of radionuclides are very important for estimation of the doses for the general public, because the present procedures recommended by the International Commission on Radiological Protection is for occupationally exposed workers and the underlying metabolic and dosimetric models have been developed from studies on adult man and experiments on adult animals and from observations on radionuclides in physico-chemically simple form. Many factors have been reported to influence the metabolic parameters. Among them, the food-chain involvement of radionuclides and the age-dependence in humans and animals are most significant as environmental and physiological factor, respectively. In connection with the age-dependence of dose calculation, the ICRP started a new programme. They organized a Task Group on Age-Dependent Dose-Factors where relevant information on metabolic and biokinetic parameters are presently being reviewed for development of a set of dose factors for the following age-groups: infant, 1-year-old, 5-year-old, 10-year-old, 15-year-old, and ICRP Reference Man. The first stage of the work is for age-dependent integrated organ and effective dose factors for radioisotopes of the following elements: hydrogen, carbon, iodine, cesium, strontium, plutonium and americium. (author)

  13. Multi-factor authentication using quantum communication

    Science.gov (United States)

    Hughes, Richard John; Peterson, Charles Glen; Thrasher, James T.; Nordholt, Jane E.; Yard, Jon T.; Newell, Raymond Thorson; Somma, Rolando D.

    2018-02-06

    Multi-factor authentication using quantum communication ("QC") includes stages for enrollment and identification. For example, a user enrolls for multi-factor authentication that uses QC with a trusted authority. The trusted authority transmits device factor information associated with a user device (such as a hash function) and user factor information associated with the user (such as an encrypted version of a user password). The user device receives and stores the device factor information and user factor information. For multi-factor authentication that uses QC, the user device retrieves its stored device factor information and user factor information, then transmits the user factor information to the trusted authority, which also retrieves its stored device factor information. The user device and trusted authority use the device factor information and user factor information (more specifically, information such as a user password that is the basis of the user factor information) in multi-factor authentication that uses QC.

  14. Rare coagulation disorders: fibrinogen, factor VII and factor XIII.

    Science.gov (United States)

    de Moerloose, P; Schved, J-F; Nugent, D

    2016-07-01

    Rare coagulation disorders (RCDs) include the inherited deficiencies of fibrinogen, factor (F) II, FV, combined FV and VIII, FVII, FX, combined FVII and X, FXI, FXIII and combined congenital deficiency of vitamin K-dependent factors (VKCFDs). Despite their rarity, a deep comprehension of all these disorders is essential to really understand haemostasis. Indeed, even if they share some common features each RCD has some particularity which makes it unique. In this review, we focus on three disorders: fibrinogen, FVII and FXIII. © 2016 John Wiley & Sons Ltd.

  15. Self-similar factor approximants

    International Nuclear Information System (INIS)

    Gluzman, S.; Yukalov, V.I.; Sornette, D.

    2003-01-01

    The problem of reconstructing functions from their asymptotic expansions in powers of a small variable is addressed by deriving an improved type of approximants. The derivation is based on the self-similar approximation theory, which presents the passage from one approximant to another as the motion realized by a dynamical system with the property of group self-similarity. The derived approximants, because of their form, are called self-similar factor approximants. These complement the obtained earlier self-similar exponential approximants and self-similar root approximants. The specific feature of self-similar factor approximants is that their control functions, providing convergence of the computational algorithm, are completely defined from the accuracy-through-order conditions. These approximants contain the Pade approximants as a particular case, and in some limit they can be reduced to the self-similar exponential approximants previously introduced by two of us. It is proved that the self-similar factor approximants are able to reproduce exactly a wide class of functions, which include a variety of nonalgebraic functions. For other functions, not pertaining to this exactly reproducible class, the factor approximants provide very accurate approximations, whose accuracy surpasses significantly that of the most accurate Pade approximants. This is illustrated by a number of examples showing the generality and accuracy of the factor approximants even when conventional techniques meet serious difficulties

  16. Factors Influencing Healthcare Service Quality

    Directory of Open Access Journals (Sweden)

    Ali Mohammad Mosadeghrad

    2014-07-01

    Full Text Available Background The main purpose of this study was to identify factors that influence healthcare quality in the Iranian context. Methods Exploratory in-depth individual and focus group interviews were conducted with 222 healthcare stakeholders including healthcare providers, managers, policy-makers, and payers to identify factors affecting the quality of healthcare services provided in Iranian healthcare organisations. Results Quality in healthcare is a production of cooperation between the patient and the healthcare provider in a supportive environment. Personal factors of the provider and the patient, and factors pertaining to the healthcare organisation, healthcare system, and the broader environment affect healthcare service quality. Healthcare quality can be improved by supportive visionary leadership, proper planning, education and training, availability of resources, effective management of resources, employees and processes, and collaboration and cooperation among providers. Conclusion This article contributes to healthcare theory and practice by developing a conceptual framework that provides policy-makers and managers a practical understanding of factors that affect healthcare service quality.

  17. TRASYS form factor matrix normalization

    Science.gov (United States)

    Tsuyuki, Glenn T.

    1992-01-01

    A method has been developed for adjusting a TRASYS enclosure form factor matrix to unity. This approach is not limited to closed geometries, and in fact, it is primarily intended for use with open geometries. The purpose of this approach is to prevent optimistic form factors to space. In this method, nodal form factor sums are calculated within 0.05 of unity using TRASYS, although deviations as large as 0.10 may be acceptable, and then, a process is employed to distribute the difference amongst the nodes. A specific example has been analyzed with this method, and a comparison was performed with a standard approach for calculating radiation conductors. In this comparison, hot and cold case temperatures were determined. Exterior nodes exhibited temperature differences as large as 7 C and 3 C for the hot and cold cases, respectively when compared with the standard approach, while interior nodes demonstrated temperature differences from 0 C to 5 C. These results indicate that temperature predictions can be artificially biased if the form factor computation error is lumped into the individual form factors to space.

  18. Peaking-factor of PWR

    International Nuclear Information System (INIS)

    Morioka, Noboru; Kato, Yasuji; Yokoi, M.

    1975-01-01

    Output peaking factor often plays an important role in the safety and operation of nuclear reactors. The meaning of the peaking factor of PWRs is categorized into two features or the peaking factor in core (FQ-core) and the peaking factor on the basis of accident analysis (or FQ-limit). FQ-core is the actual peaking factor realized in nuclear core at the time of normal operation, and FQ-limit should be evaluated from loss of coolant accident and other abnormal conditions. If FQ-core is lower than FQ-limit, the reactor may be operated at full load, but if FQ-core is larger than FQ-limit, reactor output should be controlled lower than FQ-limit. FQ-core has two kinds of values, or the one on the basis of nuclear design, and the other actually measured in reactor operation. The first FQ-core should be named as FQ-core-design and the latter as FQ-core-measured. The numerical evaluation of FQ-core-design is as follows; FQ-core-design of three-dimensions is synthesized with FQ-core horizontal value (X-Y) and FQ-core vertical value, the former one is calculated with ASSY-CORE code, and the latter one with one dimensional diffusion code. For the evaluation of FQ-core-measured, on-site data observation from nuclear reactor instrumentation or off-site data observation is used. (Iwase, T.)

  19. [Risk factors of necrotizing enterocolitis].

    Science.gov (United States)

    Tapia-Rombo, C A; Velasco-Lavín, M R; Nieto-Caldelas, A

    1993-09-01

    The purpose of the present study is to compare risk factors of necrotizing enterocolitis (NEC) between two group: group A, newborns with the disease and group B, newborns with other diseases different from NEC, in order to know if these risk factors are more frequent or not in the first group. We assessed the clinical records of all the patients hospitalized in the Neonatal Intensive Care Unit and Neonatology Service of the La Raza General Hospital between 1987 and 1991 with the diagnosis of NEC. They were compared with 65 clinical records chosen at random of patients hospitalized in the same Unit with other diagnosis at the same time, and who were discharged by improvement or deceased. In all of them were look for known risk factors for NEC generally accepted such as: prematurity, neonatal asphyxia, poliglobulia, cyanotic congenital heart disease, patent ductus arteriosus, respiratory distress syndrome, catheterization of umbilical vessels, early feeding of elevated formula increases, exchange exchange transfusion, hypoxic ischemic encephalopathy, infection, etc. Just 25 records of the possible 50 with the diagnosis of NEC full filled inclusion criteria. There were no statistically significant difference in weight, sex, mortality and known risk factors of NEC between both groups. Were concluded that NEC is a disease of unknown etiology that should be studied more thoroughly. The known risk factors must be avoided because the patient susceptibility probably play an important role.

  20. Epistaxis: Prevailing Factors and Treatment

    Directory of Open Access Journals (Sweden)

    Secchi, Myrian Marajó Dal

    2009-12-01

    Full Text Available Introduction: The epistaxis is one the most frequent otorhinolaryngologic emergencies in the medical practice. It is a benign affection, but the refractory cases require hospital admission. Objective: To evaluate prevailing factors in patients with epistaxis and treatment. Form of study: Retrospective study. Method: 60 patients with diagnosis of epistaxis were evaluated and they needed hospital admission between 2005 and 2006. Results: The main prevailing factors were: Systemic arterial hypertension 36% (n= 22, trauma 16% (n=10 and coagulopathy 5% (n=3. The treatment was the use of nasal splint: anterior 58% (n=35 and antero-posterior 27% (n=16, the electrocauterization of the identified bloody point 7% (n=4, endoscopic arterial bandage 8% (n=5 in severe epistaxis. For the patients with antero-posterior splint with recurrence of bleeding in the first 24 hours (five patients, after clinical stabilization, an arterial bandage was indicated by endoscopic means; four patients had systemic arterial hypertension and in one patient no prevailing factor was identified. Conclusion: The main associated prevailing factors were systemic arterial hypertension, trauma and coagulopathy. The treatment depends on the type, severity and cause of bleeding, initially the anterior and antero-posterior splint for bleeding control. The early endoscopic arterial bandage is indicated in patients with severe epistaxis and prevailing factors, and prolonged admission and morbidities associated with nasal splint should be avoided.