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Sample records for sch9 promotes age-dependent

  1. Interplay among Gcn5, Sch9 and mitochondria during chronological aging of wine yeast is dependent on growth conditions.

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    Cecilia Picazo

    Full Text Available Saccharomyces cerevisiae chronological life span (CLS is determined by a wide variety of environmental and genetic factors. Nutrient limitation without malnutrition, i.e. dietary restriction, expands CLS through the control of nutrient signaling pathways, of which TOR/Sch9 has proven to be the most relevant, particularly under nitrogen deprivation. The use of prototrophic wine yeast allows a better understanding of the role of nitrogen in longevity in natural and more demanding environments, such as grape juice fermentation. We previously showed that acetyltransferase Gcn5, a member of the SAGA complex, has opposite effects on CLS under laboratory and winemaking conditions, and is detrimental under the latter. Here we demonstrate that integrity of the SAGA complex is necessary for prolonged longevity, as its dismantling by SPT20 deletion causes a drop in CLS under both laboratory and winemaking conditions. The sch9Δ mutant is long-lived in synthetic SC medium, as expected, and the combined deletion of GCN5 partially suppresses this phenotype. However it is short-lived in grape juice, likely due to its low nitrogen/carbon ratio. Therefore, unbalance of nutrients can be more relevant for life span than total amounts of them. Deletion of RTG2, which codes for a protein associated with Gcn5 and is a component of the mitochondrial retrograde signal, and which communicates mitochondrial dysfunction to the nucleus, is detrimental under laboratory, but not under winemaking conditions, where respiration seems not so relevant for longevity. Transcription factor Rgm1 was found to be a novel CLS regulator Sch9-dependently.

  2. The yeast protein kinase Sch9 adjusts V-ATPase assembly/disassembly to control pH homeostasis and longevity in response to glucose availability.

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    Tobias Wilms

    2017-06-01

    Full Text Available The conserved protein kinase Sch9 is a central player in the nutrient-induced signaling network in yeast, although only few of its direct substrates are known. We now provide evidence that Sch9 controls the vacuolar proton pump (V-ATPase to maintain cellular pH homeostasis and ageing. A synthetic sick phenotype arises when deletion of SCH9 is combined with a dysfunctional V-ATPase, and the lack of Sch9 has a significant impact on cytosolic pH (pHc homeostasis. Sch9 physically interacts with, and influences glucose-dependent assembly/disassembly of the V-ATPase, thereby integrating input from TORC1. Moreover, we show that the role of Sch9 in regulating ageing is tightly connected with V-ATPase activity and vacuolar acidity. As both Sch9 and the V-ATPase are highly conserved in higher eukaryotes, it will be interesting to further clarify their cooperative action on the cellular processes that influence growth and ageing.

  3. Lipid Signaling via Pkh1/2 Regulates Fungal CO2 Sensing through the Kinase Sch9

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    Susann Pohlers

    2017-01-01

    Full Text Available Adaptation to alternating CO2 concentrations is crucial for all organisms. Carbonic anhydrases—metalloenzymes that have been found in all domains of life—enable fixation of scarce CO2 by accelerating its conversion to bicarbonate and ensure maintenance of cellular metabolism. In fungi and other eukaryotes, the carbonic anhydrase Nce103 has been shown to be essential for growth in air (~0.04% CO2. Expression of NCE103 is regulated in response to CO2 availability. In Saccharomyces cerevisiae, NCE103 is activated by the transcription factor ScCst6, and in Candida albicans and Candida glabrata, it is activated by its homologues CaRca1 and CgRca1, respectively. To identify the kinase controlling Cst6/Rca1, we screened an S. cerevisiae kinase/phosphatase mutant library for the ability to regulate NCE103 in a CO2-dependent manner. We identified ScSch9 as a potential ScCst6-specific kinase, as the sch9Δ mutant strain showed deregulated NCE103 expression on the RNA and protein levels. Immunoprecipitation revealed the binding capabilities of both proteins, and detection of ScCst6 phosphorylation by ScSch9 in vitro confirmed Sch9 as the Cst6 kinase. We could show that CO2-dependent activation of Sch9, which is part of a kinase cascade, is mediated by lipid/Pkh1/2 signaling but not TORC1. Finally, we tested conservation of the identified regulatory cascade in the pathogenic yeast species C. albicans and C. glabrata. Deletion of SCH9 homologues of both species impaired CO2-dependent regulation of NCE103 expression, which indicates a conservation of the CO2 adaptation mechanism among yeasts. Thus, Sch9 is a Cst6/Rca1 kinase that links CO2 adaptation to lipid signaling via Pkh1/2 in fungi.

  4. The Aspergillus fumigatus SchASCH9 kinase modulates SakAHOG1 MAP kinase activity and it is essential for virulence.

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    Alves de Castro, Patrícia; Dos Reis, Thaila Fernanda; Dolan, Stephen K; Oliveira Manfiolli, Adriana; Brown, Neil Andrew; Jones, Gary W; Doyle, Sean; Riaño-Pachón, Diego M; Squina, Fábio Márcio; Caldana, Camila; Singh, Ashutosh; Del Poeta, Maurizio; Hagiwara, Daisuke; Silva-Rocha, Rafael; Goldman, Gustavo H

    2016-11-01

    The serine-threonine kinase TOR, the Target of Rapamycin, is an important regulator of nutrient, energy and stress signaling in eukaryotes. Sch9, a Ser/Thr kinase of AGC family (the cAMP-dependent PKA, cGMP- dependent protein kinase G and phospholipid-dependent protein kinase C family), is a substrate of TOR. Here, we characterized the fungal opportunistic pathogen Aspergillus fumigatus Sch9 homologue (SchA). The schA null mutant was sensitive to rapamycin, high concentrations of calcium, hyperosmotic stress and SchA was involved in iron metabolism. The ΔschA null mutant showed increased phosphorylation of SakA, the A. fumigatus Hog1 homologue. The schA null mutant has increased and decreased trehalose and glycerol accumulation, respectively, suggesting SchA performs different roles for glycerol and trehalose accumulation during osmotic stress. The schA was transcriptionally regulated by osmotic stress and this response was dependent on SakA and MpkC. The double ΔschA ΔsakA and ΔschA ΔmpkC mutants were more sensitive to osmotic stress than the corresponding parental strains. Transcriptomics and proteomics identified direct and indirect targets of SchA post-exposure to hyperosmotic stress. Finally, ΔschA was avirulent in a low dose murine infection model. Our results suggest there is a complex network of interactions amongst the A. fumigatus TOR, SakA and SchA pathways. © 2016 John Wiley & Sons Ltd.

  5. Lipid Signaling via Pkh1/2 Regulates Fungal CO2 Sensing through the Kinase Sch9.

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    Pohlers, Susann; Martin, Ronny; Krüger, Thomas; Hellwig, Daniela; Hänel, Frank; Kniemeyer, Olaf; Saluz, Hans Peter; Van Dijck, Patrick; Ernst, Joachim F; Brakhage, Axel; Mühlschlegel, Fritz A; Kurzai, Oliver

    2017-01-31

    Adaptation to alternating CO 2 concentrations is crucial for all organisms. Carbonic anhydrases-metalloenzymes that have been found in all domains of life-enable fixation of scarce CO 2 by accelerating its conversion to bicarbonate and ensure maintenance of cellular metabolism. In fungi and other eukaryotes, the carbonic anhydrase Nce103 has been shown to be essential for growth in air (~0.04% CO 2 ). Expression of NCE103 is regulated in response to CO 2 availability. In Saccharomyces cerevisiae, NCE103 is activated by the transcription factor ScCst6, and in Candida albicans and Candida glabrata, it is activated by its homologues CaRca1 and CgRca1, respectively. To identify the kinase controlling Cst6/Rca1, we screened an S. cerevisiae kinase/phosphatase mutant library for the ability to regulate NCE103 in a CO 2 -dependent manner. We identified ScSch9 as a potential ScCst6-specific kinase, as the sch9Δ mutant strain showed deregulated NCE103 expression on the RNA and protein levels. Immunoprecipitation revealed the binding capabilities of both proteins, and detection of ScCst6 phosphorylation by ScSch9 in vitro confirmed Sch9 as the Cst6 kinase. We could show that CO 2 -dependent activation of Sch9, which is part of a kinase cascade, is mediated by lipid/Pkh1/2 signaling but not TORC1. Finally, we tested conservation of the identified regulatory cascade in the pathogenic yeast species C. albicans and C. glabrata Deletion of SCH9 homologues of both species impaired CO 2 -dependent regulation of NCE103 expression, which indicates a conservation of the CO 2 adaptation mechanism among yeasts. Thus, Sch9 is a Cst6/Rca1 kinase that links CO 2 adaptation to lipid signaling via Pkh1/2 in fungi. All living organisms have to cope with alternating CO 2 concentrations as CO 2 levels range from very low in the atmosphere (0.04%) to high (5% and more) in other niches, including the human body. In fungi, CO 2 is sensed via two pathways. The first regulates virulence in

  6. Mitochondrial genomic dysfunction causes dephosphorylation of Sch9 in the yeast Saccharomyces cerevisiae.

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    Kawai, Shigeyuki; Urban, Jörg; Piccolis, Manuele; Panchaud, Nicolas; De Virgilio, Claudio; Loewith, Robbie

    2011-10-01

    TORC1-dependent phosphorylation of Saccharomyces cerevisiae Sch9 was dramatically reduced upon exposure to a protonophore or in respiration-incompetent ρ(0) cells but not in respiration-incompetent pet mutants, providing important insight into the molecular mechanisms governing interorganellar signaling in general and retrograde signaling in particular.

  7. Local application of SCH 39166 reversibly and dose-dependently decreases acetylcholine release in the rat striatum.

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    Acquas, E; Di Chiara, G

    1999-11-03

    The effect of local application by reverse dialysis of the dopamine D(1) receptor antagonist (-)-trans-6,7,7a,8,9, 13b-exahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo-[d]-nap hto-[2, 1b]-azepine hydrochloride (SCH 39166) on acetylcholine release was studied in awake, freely moving rats implanted with concentric microdialysis probes in the dorsal striatum. In these experiments, the reversible acetylcholine esterase inhibitor, neostigmine, was added to the perfusion solution at two different concentrations, 0.01 and 0.1 microM. SCH 39166 (1, 5 and 10 microM), in the presence of 0.01 microM neostigmine, reversibly decreased striatal acetylcholine release (1 microM SCH 39166 by 8+/-4%; 5 microM SCH 39166 by 24+/-5%; 10 microM SCH 39166 by 27+/-7%, from basal). Similarly, SCH 39166, applied in the presence of a higher neostigmine concentration (0.1 microM), decreased striatal acetylcholine release by 14+/-4% at 1 microM, by 28+/-8% at 5 microM and by 30+/-5% at 10 microM, in a dose-dependent and time-dependent manner. These results are consistent with the existence of a facilitatory tone of dopamine on striatal acetylcholine transmission mediated by dopamine D(1) receptors located on striatal cholinergic interneurons.

  8. Experimental Evolution Reveals Interplay between Sch9 and Polyploid Stability in Yeast.

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    Yi-Jin Lu

    2016-11-01

    Full Text Available Polyploidization has crucial impacts on the evolution of different eukaryotic lineages including fungi, plants and animals. Recent genome data suggest that, for many polyploidization events, all duplicated chromosomes are maintained and genome reorganizations occur much later during evolution. However, newly-formed polyploid genomes are intrinsically unstable and often quickly degenerate into aneuploidy or diploidy. The transition between these two states remains enigmatic. In this study, laboratory evolution experiments were conducted to investigate this phenomenon. We show that robust tetraploidy is achieved in evolved yeast cells by increasing the abundance of Sch9-a protein kinase activated by the TORC1 (Target of Rapamycin Complex 1 and other signaling pathways. Overexpressing SCH9, but not TOR1, allows newly-formed tetraploids to exhibit evolved phenotypes and knocking out SCH9 diminishes the evolved phenotypes. Furthermore, when cells were challenged with conditions causing ancestral cells to evolve aneuploidy, tetraploidy was maintained in the evolved lines. Our results reveal a determinant role for Sch9 during the early stage of polyploid evolution.

  9. Tor1/Sch9-regulated carbon source substitution is as effective as calorie restriction in life span extension.

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    Min Wei

    2009-05-01

    Full Text Available The effect of calorie restriction (CR on life span extension, demonstrated in organisms ranging from yeast to mice, may involve the down-regulation of pathways, including Tor, Akt, and Ras. Here, we present data suggesting that yeast Tor1 and Sch9 (a homolog of the mammalian kinases Akt and S6K is a central component of a network that controls a common set of genes implicated in a metabolic switch from the TCA cycle and respiration to glycolysis and glycerol biosynthesis. During chronological survival, mutants lacking SCH9 depleted extracellular ethanol and reduced stored lipids, but synthesized and released glycerol. Deletion of the glycerol biosynthesis genes GPD1, GPD2, or RHR2, among the most up-regulated in long-lived sch9Delta, tor1Delta, and ras2Delta mutants, was sufficient to reverse chronological life span extension in sch9Delta mutants, suggesting that glycerol production, in addition to the regulation of stress resistance systems, optimizes life span extension. Glycerol, unlike glucose or ethanol, did not adversely affect the life span extension induced by calorie restriction or starvation, suggesting that carbon source substitution may represent an alternative to calorie restriction as a strategy to delay aging.

  10. Relationship between age and promotion orientation depends on perceived older worker stereotypes.

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    Bowen, Catherine E; Staudinger, Ursula M

    2013-01-01

    Research has consistently revealed a negative relationship between chronological age and promotion orientation, that is, the motivational orientation toward approaching possible gains. In addition, experimental research has demonstrated that activating positive self-relevant stereotypes (e.g., for men, the stereotype that men are good at math) can stimulate increases in promotion orientation. Integrating and applying this research to the work context, we hypothesized that the relationship between age and promotion orientation would depend on employees' perceptions of the stereotype of older workers in their work context, such that there would be no negative relationship between age and promotion orientation when individuals perceive a more positive older worker stereotype. We analyzed the relationships between age, perceived older worker stereotype (POWS), and promotion orientation using a sample of working adults (N = 337) aged 19-64 years. Results revealed a significant age by POWS interaction such that there was a negative relationship between age and promotion orientation when POWS was less positive. However, there was no relationship between age and promotion orientation when POWS was more positive. Results suggest that the negative relationship between age and promotion orientation depends on contextual factors such as POWS.

  11. Synthesis and structure of PbBipy2(1-B10H9S(CH3)2)2

    International Nuclear Information System (INIS)

    Orlova, A.M.; Sivaev, I.B.; Lagun, V.L.; Katser, S.B.; Solntsev, K.A.; Kuznetsov, N.T.

    1993-01-01

    Lead complex with B 10 H 9 S(CH 3 ) 2 - anion and 2,2'-bipyridine was synthesized and characterized. According to the data of X-ray diffraction analysis the crystals belong to monoclinic crystal system, sp. gr. P2 1 /a: a = 9.940(4), b 31.568(4), c = 13.458(2) A, β = 111.09(2) deg, V = 3940(2) A 3 , Z = 4. The structure consists of monomer units PbBipy 2 (1-B 10 H 9 S(CH 3 ) 2 ) 2 . The Pb-B distances are within 3.24-3.55 A. 15 refs., 1 fig., 2 tabs

  12. Protein kinase FgSch9 serves as a mediator of the target of rapamycin and high osmolarity glycerol pathways and regulates multiple stress responses and secondary metabolism in Fusarium graminearum.

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    Gu, Qin; Zhang, Chengqi; Yu, Fangwei; Yin, Yanni; Shim, Won-Bo; Ma, Zhonghua

    2015-08-01

    Saccharomyces cerevisiae protein kinase Sch9 is one of the downstream effectors of the target of rapamycin (TOR) complex 1 and plays multiple roles in stress resistance, longevity and nutrient sensing. However, the functions of Sch9 orthologs in filamentous fungi, particularly in pathogenic species, have not been characterized to date. Here, we investigated biological and genetic functions of FgSch9 in Fusarium graminearum. The FgSCH9 deletion mutant (ΔFgSch9) was defective in aerial hyphal growth, hyphal branching and conidial germination. The mutant exhibited increased sensitivity to osmotic and oxidative stresses, cell wall-damaging agents, and to rapamycin, while showing increased thermal tolerance. We identified FgMaf1 as one of the FgSch9-interacting proteins that plays an important role in regulating mycotoxin biosynthesis and virulence of F. graminearum. Co-immunoprecipitation and affinity capture-mass spectrometry assays showed that FgSch9 also interacts with FgTor and FgHog1. More importantly, both ΔFgSch9 and FgHog1 null mutant (ΔFgHog1) exhibited increased sensitivity to osmotic and oxidative stresses. This defect was more severe in the FgSch9/FgHog1 double mutant. Taken together, we propose that FgSch9 serves as a mediator of the TOR and high osmolarity glycerol pathways, and regulates vegetative differentiation, multiple stress responses and secondary metabolism in F. graminearum. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

  13. The canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner

    International Nuclear Information System (INIS)

    Yano, Fumiko; Kugimiya, Fumitaka; Ohba, Shinsuke; Ikeda, Toshiyuki; Chikuda, Hirotaka; Ogasawara, Toru; Ogata, Naoshi; Takato, Tsuyoshi; Nakamura, Kozo; Kawaguchi, Hiroshi; Chung, Ung-il

    2005-01-01

    To better understand the role of the canonical Wnt signaling pathway in cartilage development, we adenovirally expressed a constitutively active (Canada) or a dominant negative (dn) form of lymphoid enhancer factor-1 (LEF-1), the main nuclear effector of the pathway, in undifferentiated mesenchymal cells, chondrogenic cells, and primary chondrocytes, and examined the expression of markers for chondrogenic differentiation and hypertrophy. caLEF-1 and LiCl, an activator of the canonical pathway, promoted both chondrogenic differentiation and hypertrophy, whereas dnLEF-1 and the gene silencing of β-catenin suppressed LiCl-promoted effects. To investigate whether these effects were dependent on Sox9, a master regulator of cartilage development, we stimulated Sox9-deficient ES cells with the pathway. caLEF-1 and LiCl promoted both chondrogenic differentiation and hypertrophy in wild-type, but not in Sox9-deficient, cells. The response of Sox9-deficient cells was restored by the adenoviral expression of Sox9. Thus, the canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner

  14. Molecular structures of Se(SCH3)2 and Te(SCH3)2 using gas-phase electron diffraction and ab initio and DFT geometry optimisations.

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    Fleischer, Holger; Wann, Derek A; Hinchley, Sarah L; Borisenko, Konstantin B; Lewis, James R; Mawhorter, Richard J; Robertson, Heather E; Rankin, David W H

    2005-10-07

    The molecular structures of Se(SCH(3))(2) and Te(SCH(3))(2) were investigated using gas-phase electron diffraction (GED) and ab initio and DFT geometry optimisations. While parameters involving H atoms were refined using flexible restraints according to the SARACEN method, parameters that depended only on heavy atoms could be refined without restraints. The GED-determined geometric parameters (r(h1)) are: rSe-S 219.1(1), rS-C 183.2(1), rC-H 109.6(4) pm; angleS-Se-S 102.9(3), angleSe-S-C 100.6(2), angleS-C-H (mean) 107.4(5), phiS-Se-S-C 87.9(20), phiSe-S-C-H 178.8(19) degrees for Se(SCH(3))(2), and rTe-S 238.1(2), rS-C 184.1(3), rC-H 110.0(6) pm; angleS-Te-S 98.9(6), angleTe-S-C 99.7(4), angleS-C-H (mean) 109.2(9), phiS-Te-S-C 73.0(48), phiTe-S-C-H 180.1(19) degrees for Te(SCH(3))(2). Ab initio and DFT calculations were performed at the HF, MP2 and B3LYP levels, employing either full-electron basis sets [3-21G(d) or 6-31G(d)] or an effective core potential with a valence basis set [LanL2DZ(d)]. The best fit to the GED structures was achieved at the MP2 level. Differences between GED and MP2 results for rS-C and angleS-Te-S were explained by the thermal population of excited vibrational states under the experimental conditions. All theoretical models agreed that each compound exists as two stable conformers, one in which the methyl groups are on the same side (g(+)g(-) conformer) and one in which they are on different sides (g(+)g(+) conformer) of the S-Y-S plane (Y = Se, Te). The conformational composition under the experimental conditions could not be resolved from the GED data. Despite GED R-factors and ab initio and DFT energies favouring the g(+)g(+) conformer, it is likely that both conformers are present, for Se(SCH(3))(2) as well as for Te(SCH(3))(2).

  15. pH homeostasis links the nutrient sensing PKA/TORC1/Sch9 ménage-à-trois to stress tolerance and longevity.

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    Deprez, Marie-Anne; Eskes, Elja; Wilms, Tobias; Ludovico, Paula; Winderickx, Joris

    2018-01-12

    The plasma membrane H + -ATPase Pma1 and the vacuolar V-ATPase act in close harmony to tightly control pH homeostasis, which is essential for a vast number of physiological processes. As these main two regulators of pH are responsive to the nutritional status of the cell, it seems evident that pH homeostasis acts in conjunction with nutrient-induced signalling pathways. Indeed, both PKA and the TORC1-Sch9 axis influence the proton pumping activity of the V-ATPase and possibly also of Pma1. In addition, it recently became clear that the proton acts as a second messenger to signal glucose availability via the V-ATPase to PKA and TORC1-Sch9. Given the prominent role of nutrient signalling in longevity, it is not surprising that pH homeostasis has been linked to ageing and longevity as well. A first indication is provided by acetic acid, whose uptake by the cell induces toxicity and affects longevity. Secondly, vacuolar acidity has been linked to autophagic processes, including mitophagy. In agreement with this, a decline in vacuolar acidity was shown to induce mitochondrial dysfunction and shorten lifespan. In addition, the asymmetric inheritance of Pma1 has been associated with replicative ageing and this again links to repercussions on vacuolar pH. Taken together, accumulating evidence indicates that pH homeostasis plays a prominent role in the determination of ageing and longevity, thereby providing new perspectives and avenues to explore the underlying molecular mechanisms.

  16. The new Federal Act for the protection against nuisances (BImSchV)

    International Nuclear Information System (INIS)

    Froeba, K.; Thomas, L.

    1977-01-01

    Text of the decree with introduction and comprehensive explanations. Furnaces (1st decree of BImSchV); Chemical purification installations (2nd decree of BImSchV); sulfur content of light fuel oil and diesel oil (3rd decree of BImSchV); installations subject to licensing (4th decree of BImSchV); persons authorized with the protection against nuisances (5th decree of BImSchV); know-how and reliability of these persons (6th decree of BImSchV); ejection limitation for wood dust (7th decree of BImSchV); limitation of noise made by lawn mowing machines (8th decree of BImSchV); principles of the licensing procedure (9th decree of BImSchV). Text of the Federal Act for the Protection Against Nuisances. (orig.) [de

  17. pH homeostasis links the nutrient sensing PKA/TORC1/Sch9 ménage-à-trois to stress tolerance and longevity

    Directory of Open Access Journals (Sweden)

    Marie-Anne Deprez

    2018-01-01

    Full Text Available The plasma membrane H+-ATPase Pma1 and the vacuolar V-ATPase act in close harmony to tightly control pH homeostasis, which is essential for a vast number of physiological processes. As these main two regulators of pH are responsive to the nutritional status of the cell, it seems evident that pH homeostasis acts in conjunction with nutrient-induced signalling pathways. Indeed, both PKA and the TORC1-Sch9 axis influence the proton pumping activity of the V-ATPase and possibly also of Pma1. In addition, it recently became clear that the proton acts as a second messenger to signal glucose availability via the V-ATPase to PKA and TORC1-Sch9. Given the prominent role of nutrient signalling in longevity, it is not surprising that pH homeostasis has been linked to ageing and longevity as well. A first indication is provided by acetic acid, whose uptake by the cell induces toxicity and affects longevity. Secondly, vacuolar acidity has been linked to autophagic processes, including mitophagy. In agreement with this, a decline in vacuolar acidity was shown to induce mitochondrial dysfunction and shorten lifespan. In addition, the asymmetric inheritance of Pma1 has been associated with replicative ageing and this again links to repercussions on vacuolar pH. Taken together, accumulating evidence indicates that pH homeostasis plays a prominent role in the determination of ageing and longevity, thereby providing new perspectives and avenues to explore the underlying molecular mechanisms.

  18. In vivo binding of a radioiodinated derivative of SCH 23390 (SCH)

    International Nuclear Information System (INIS)

    McQuade, R.D.; Iorio, L.C.; Chipkin, R.E.; Barnett, A.

    1986-01-01

    The in vitro binding properties of SCH have been extensively characterized, however, little research has been conducted on its in vivo binding profile. This report is on the characterization of the in vivo binding of 7- 125 I-SCH (71 SCH), which possesses a specific radioactivity of 2200 Ci/mmole and exhibits in vitro binding properties similar to those of 3 H-SCH. Sprague-Dawley rats were injected with 0.02 nmoles of 7ISH, in the absence and presence of 30 nmoles of unlabeled SCH, and were sacrificed at 1,2 and 4 hours post-treatment. The striatum and cerebellum were removed, weighed and the radioactivity was counted. Specific binding was defined as cpm in the absence of SCH less cpm in the presence of SCH. One hour after injection, the striatum of the rats treated with 7ISCH contained 170,000 cpm/g tissue, of which 105,000 cpm/g tissue were specific. The cerebellum of the rats contained 75% fewer cpm/g tissue and did not exhibit specifically bound in the striatum, but not in the cerebellum. Sacrifice after longer periods of time resulted in a 35% decrease in specific binding between 1 and 2 h, and a 70% decrease between 1 and 4 h. The pharmacological profile of the in vivo binding of 7ISCH was determined by the ability of dopaminergic antagonists to inhibit specific binding in the rat striatum 1 h after treatment. Thirty nmoles of SCH caused a 55% inhibition of the specific binding to striatum, while an equal amount of SCH 23388, the inactive S isomer of SCH, resulted in no inhibition. Haloperidol, a D-2 antagonist, did not inhibit the specific binding of 7ISCH to the striatum at doses up to 3000 nmoles. These data indicate that 7ISCH is specifically bound, in vivo, to D-1 receptors in the rat striatum

  19. SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infection in vitro and in vivo.

    Science.gov (United States)

    Strizki, J M; Xu, S; Wagner, N E; Wojcik, L; Liu, J; Hou, Y; Endres, M; Palani, A; Shapiro, S; Clader, J W; Greenlee, W J; Tagat, J R; McCombie, S; Cox, K; Fawzi, A B; Chou, C C; Pugliese-Sivo, C; Davies, L; Moreno, M E; Ho, D D; Trkola, A; Stoddart, C A; Moore, J P; Reyes, G R; Baroudy, B M

    2001-10-23

    We describe here the identification and properties of SCH-C (SCH 351125), a small molecule inhibitor of HIV-1 entry via the CCR5 coreceptor. SCH-C, an oxime-piperidine compound, is a specific CCR5 antagonist as determined in multiple receptor binding and signal transduction assays. This compound specifically inhibits HIV-1 infection mediated by CCR5 in U-87 astroglioma cells but has no effect on infection of CXCR4-expressing cells. SCH-C has broad and potent antiviral activity in vitro against primary HIV-1 isolates that use CCR5 as their entry coreceptor, with mean 50% inhibitory concentrations ranging between 0.4 and 9 nM. Moreover, SCH-C strongly inhibits the replication of an R5-using HIV-1 isolate in SCID-hu Thy/Liv mice. SCH-C has a favorable pharmacokinetic profile in rodents and primates with an oral bioavailability of 50-60% and a serum half-life of 5-6 h. On the basis of its novel mechanism of action, potent antiviral activity, and in vivo pharmacokinetic profile, SCH-C is a promising new candidate for therapeutic intervention of HIV infection.

  20. Henoch-Schönlein Purpura

    DEFF Research Database (Denmark)

    Hetland, Liv Eline; Susrud, Kjærsti Sørensen; Lindahl, Kim Hein

    2017-01-01

    Henoch-Schönlein purpura is the most common childhood vasculitis, but may also affect adults. This article reviews the literature since 2011 on advances in diagnosis, clinical disease manifestations, pathophysiology and treatment of Henoch-Schönlein purpura. The clinical manifestations are thought...... studies are needed to confirm these findings. Cancer screening should be considered in older males diagnosed with Henoch-Schönlein purpura....

  1. Federal Act on Protection against Nuisances (BImSchG) and supplementing regulations. 9. ed.

    International Nuclear Information System (INIS)

    Hansmann, K.

    1992-01-01

    This handy booklet contains the BImSchG and related implementing regulations as well as the Technical Codes Clean Air and Noise Abatement. The contribution on the BImSchG explains the origin of the Act, the scope of application, its concept and principles. The contents of the Act is portrayed by emphasizing subject-related connections. Dealt with are also regulations for installations requiring licensing, the measurement of airborne pollution, stipulations concerning the area of installations and transport, as well as the regulation concerning the monitoring of airborne pollution in the Federal Republic of Germany. (orig.) [de

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

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    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.

  3. Age of onset as a risk factor of renal involvement in Henoch-Schönlein purpura

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    Ledika, Masayu Amanda; Sapartini, Gartika; Setiabudiawan, Budi

    2014-01-01

    Background Henoch-Schönlein purpura (HSP) is the most common vasculitis in children, characterized by triad of symptoms; palpable purpura without thrombocytopenia, abdominal pain, and arthritis. Renal involvement often occur in children with HSP. No data on the renal involvement of children with HSP in Indonesia, especially West Java. Objective To evaluate renal involvement in children with HSP. Methods Retrospective study was conducted in children with HSP in Department of Child Health, Hasan Sadikin Hospital, from 2006 to 2011. Characteristics and clinical manifestations was reviewed from medical record. HSP was diagnosed by American College of Rheumatology 1990 criteria or European League Against Rheumatism/Pediatric Rheumatology International Trials Organization/Pediatric Rheumatology European Society 2008. Results There were 128 patients, consisting of 82 male (64.9%) and 46 female (35.1%) with ratio 1.8:1. Mean age was 7.9 ± 2.9 years old which range from 6 month to 15 years. Peak morbidity was between 5-10 years old. Prevalence of HSP in Hasan Sadikin Hospital tend to raise from 2.7/100,000 in 2008 to 5.2/100,000 in 2010. In most patients (71%) purpura was the first symptom. Seventy-one patients (44.5%) had arthritis and 89 patients (69.5%) had abdominal pain, while renal involvement was in 28 patients (21.8%). Gastrointestinal manifestations tend to manifest in patients less than 5 years old (p = 0.267), while renal involvement tend to manifest in age group 11-15 years old (p = 0.015) with odds ratio 3.1 (95% confidence interval, 1.2-8.1). Conclusion Renal involvement in children with HSP is more common in age group 11 to 15 years old. PMID:24527410

  4. Henoch-Schönlein Purpura in Northern Spain

    Science.gov (United States)

    Calvo-Río, Vanesa; Loricera, Javier; Mata, Cristina; Martín, Luis; Ortiz-Sanjuán, Francisco; Alvarez, Lino; González-Vela, M. Carmen; González-Lamuño, Domingo; Rueda-Gotor, Javier; Fernández-Llaca, Héctor; González-López, Marcos A.; Armesto, Susana; Peiró, Enriqueta; Arias, Manuel; González-Gay, Miguel A.; Blanco, Ricardo

    2014-01-01

    Abstract The severity of clinical features and the outcomes in previous series of patients reported with Henoch-Schönlein purpura (HSP) vary greatly, probably due to selection bias. To establish the actual clinical spectrum of HSP in all age groups using an unselected and wide series of patients diagnosed at a single center, we performed a retrospective review of 417 patients classified as having HSP according to the criteria proposed by Michel et al. Of 417 patients, 240 were male and 177 female, with a median age at the time of disease diagnosis of 7.5 years (interquartile range [IQR], 5.3–20.1 yr). Three-quarters of the patients were children or young people aged 20 years or younger (n = 315), and one-quarter were adults (n = 102). The most frequent precipitating events were a previous infection (38%), usually an upper respiratory tract infection, and/or drug intake (18.5%) shortly before the onset of the vasculitis. At disease onset the most common manifestations were skin lesions (55.9%), nephropathy (24%), gastrointestinal involvement (13.7%), joint symptoms (9.1%), and fever (6.2%). Cutaneous involvement occurring in all patients, mainly purpuric skin lesion, was the most common manifestation when the vasculitis was fully established, followed by gastrointestinal (64.5%), joint (63.1%), and renal involvement (41.2%). The main laboratory findings were leukocytosis (36.7%), anemia (8.9%), and increased serum IgA levels (31.7%). The most frequent therapies used were corticosteroids (35%), nonsteroidal antiinflammatory drugs (14%), and cytotoxic agents (5%). After a median follow-up of 12 months (IQR, 2–38 mo), complete recovery was observed in most cases (n = 346; 83.2%), while persistent, usually mild, nephropathy was observed in only 32 (7.7%) cases. Relapses were observed in almost a third of patients (n = 133; 31.9%). In conclusion, although HSP is a typical vasculitis affecting children and young people, it is not uncommon in adults. The prognosis is

  5. Dopamine1 receptors in rat kidneys identified with 125I-Sch 23982

    International Nuclear Information System (INIS)

    Felder, R.A.; Jose, P.A.

    1988-01-01

    Dopamine1 receptors were studied in rat kidney using the selective dopamine1 antagonist 125I-labeled Sch 23982. The specific binding of 125I-Sch 23982 (defined by 5 microM Sch 23390) to renal cortical homogenates incubated at room temperature was rapid, saturable with time and ligand concentration, and reversible. Analysis of Rosenthal plots revealed a single class of receptors with an apparent dissociation constant of 12.2 +/- 1.9 nM and maximum receptor density of 1.03 +/- 0.15 pmol/mg protein (n = 6). However, competition experiments with the dopamine1 antagonist Sch 23390 revealed a low- and high-affinity binding site with inhibition constants of 1 x 10(-6) and 1 x 10(-8) M, respectively. The competition experiments were also indicative of dopamine1 receptors with stereoselectivity noted for dopamine1 but not for dopamine2 antagonists. The inhibition constants for dopamine1 antagonists and agonists were two orders of magnitude greater in renal cortical than striatal homogenates. Different buffers affected striatal but not renal cortical binding. Autoradiographic studies revealed 125I-Sch 23982 binding in renal cortical but not medullary tissue. These studies confirm the presence of dopamine1 receptors in the cortex of the rat kidney

  6. Prevalence and Characteristics of Nonblanching, Palpable Skin Lesions With a Linear Pattern in Children With Henoch-Schönlein Syndrome.

    Science.gov (United States)

    Milani, Gregorio P; Lava, Sebastiano A G; Ramelli, Vera; Bianchetti, Mario G

    2017-11-01

    Linear nonblanching skin lesions are thought to occur very rarely in patients with Henoch-Schönlein syndrome. To examine the prevalence and characteristics of linear nonblanching skin lesions in children with Henoch-Schönlein syndrome. A prospective case series was conducted at the ambulatory practice of a hospitalist between January 1, 2010, and December 31, 2015, among 31 consecutive children with Henoch-Schönlein syndrome. Thirty-one consecutive children affected with Henoch-Schönlein syndrome who were from 3.0 to 12.0 years of age (median age, 6.2 years). Children with Henoch-Schönlein syndrome underwent a careful, structured skin examination established in advance with emphasis on the presence of palpable lesions with a linear pattern. Among the 31 children in the study (12 girls and 19 boys; median age, 6.2 years [range, 3.0-12.0 years]), 8 (26%) had linear lesions on the legs, groin, waistline, wrists, or forearms. Patients with or without linear lesions did not differ significantly with respect to sex, age, and cutaneous, abdominal, articular, or renal involvement. This study illustrates the prevalence and characteristics of linear skin lesions in patients with Henoch-Schönlein syndrome. Patients with symptoms suggestive of this vasculitis should be evaluated for the presence of nonblanching, palpable lesions with a linear pattern.

  7. Atmospheric chemistry of dimethyl sulfide. Kinetics of the CH3SCH2O2 + NO2 reaction in the gas phase at 296 K

    DEFF Research Database (Denmark)

    Nielsen, O.J.; Sehested, J.; Wallington, T.J.

    1995-01-01

    The pulse radiolysis of SF6/CH3SCH3/O-2/NO2 gas mixtures was used to generate CH3SCH2O2 radicals in the presence of NO2. By monitoring the rate of NO2 decay using its absorption at 400 nm, rate constants for the reaction of CH3SCH2O2 radicals with NO2 were measured to be (9.2 +/- 0.9) x 10...

  8. Arnold Schőnberg - analiza Klavirske suite opus 25

    OpenAIRE

    Voler, Saša

    2018-01-01

    Magistrsko delo vsebuje oris življenja Arnolda Schönberga in njegovega glasbenega opusa. Arnolda Schönberga spoznamo kot učenca in kot učitelja, spoznamo ga kot abstraktnega človeka, ki se bojuje s triskaidekafobijo, ki ima velik vpliv na njegova dela. V magistrskem delu je tudi razlaga Schönbergovih odnosov s skladatelji njegovega kroga, ki so nanj tako ali drugače vplivali, hkrati pa spoznamo, da se je Schönberg posvečal tudi slikarstvu. V začetnem opisu glasbe 20.stoletja spoznamo obdobje,...

  9. Henoch Schönlein purpura associated with pulmonary adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Tetsuka Takafumi

    2011-06-01

    Full Text Available Abstract Introduction Henoch-Schönlein purpura is a common immunoglobulin A-mediated vasculitis syndrome in children. Henoch-Schönlein purpura can also affect adults and is probably related to malignancy. Case presentation We report the case of a 61-year-old Japanese man who presented for examination after an abnormal shadow was detected by chest radiography. He received a diagnosis of pulmonary adenocarcinoma, stage IV. Purpura on the legs, abdominal pain, diarrhea, hematuria and proteinuria developed at this time. Henoch-Schönlein purpura was diagnosed, base on the clinical symptoms and histological findings of biopsy specimens of the skin, which showed vasculitis with immunoglobulin A deposits. Our patient received chemotherapy with gemcitabine after successful steroid therapy for the Henoch-Schönlein purpura. Conclusion Although hematological malignancies are well-known causes of vasculitides, cases of Henoch-Schönlein purpura associated with lung adenocarcinoma are rare. Our patient was treated with corticosteroid therapy, which cleared the purpura and cytotoxic chemotherapy for the non-small cell lung cancer. However, he died from heart failure due to cardiac tamponade.

  10. Posaconazole (Noxafil, SCH 56592), a new azole antifungal drug, was a discovery based on the isolation and mass spectral characterization of a circulating metabolite of an earlier lead (SCH 51048).

    Science.gov (United States)

    Nomeir, Amin A; Pramanik, Birendra N; Heimark, Larry; Bennett, Frank; Veals, John; Bartner, Peter; Hilbert, Maryjane; Saksena, Anil; McNamara, Paul; Girijavallabhan, Viyyoor; Ganguly, Ashit K; Lovey, Raymond; Pike, Russell; Wang, Haiyan; Liu, Yi-Tsung; Kumari, Pramila; Korfmacher, Walter; Lin, Chin-Chung; Cacciapuoti, Anthony; Loebenberg, David; Hare, Roberta; Miller, George; Pickett, Cecil

    2008-04-01

    Posaconazole (SCH 56592) is a novel triazole antifungal drug that is marketed in Europe and the United States under the trade name 'Noxafil' for prophylaxis against invasive fungal infections. SCH 56592 was discovered as a possible active metabolite of SCH 51048, an earlier lead. Initial studies have shown that serum concentrations determined by a microbiological assay were higher than those determined by HPLC from animals dosed with SCH 51048. Subsequently, several animals species were dosed with (3)H-SCH 51048 and the serum was analyzed for total radioactivity, SCH 51048 concentration and antifungal activity. The antifungal activity was higher than that expected based on SCH 51048 serum concentrations, confirming the presence of active metabolite(s). Metabolite profiling of serum samples at selected time intervals pinpointed the peak that was suspected to be the active metabolite. Consequently, (3)H-SCH 51048 was administered to a large group of mice, the serum was harvested and the metabolite was isolated by extraction and semipreparative HPLC. LC-MS/MS analysis suggested that the active metabolite is a secondary alcohol with the hydroxyl group in the aliphatic side chain of SCH 51048. All corresponding monohydroxylated diastereomeric mixtures were synthesized and characterized. The HPLC retention time and LC-MS/MS spectra of the diastereomeric secondary alcohols of SCH 51048 were similar to those of the isolated active metabolite. Finally, all corresponding individual monohydroxylated diasteriomers were synthesized and evaluated for in vitro and in vivo antifungal potencies, as well as pharmacokinetics. SCH 56592 emerged as the candidate with the best overall profile.

  11. Reflections on the Schön affair

    Science.gov (United States)

    Brandon, David; Santic, Branko

    2009-07-01

    In her feature article on the fraud perpetrated by Jan Hendrik Schön (May pp24-29), Eugenie Samuel Reich concludes that the fake data Schön generated at Bell Labs were designed primarily to meet the expectations of his peers. She is probably right, but the Schön case was by no means the first of its kind. A century ago the Piltdown fraud, in which medieval cranial fragments were matched with part of an orang-utan jaw bone, convinced British archaeologists and palaeontologists that early hominids developed on the South Downs. The scientific evidence was never fully accepted outside the British Empire, but it still took the UK's Natural History Museum 50 years to recognize the hoax. "Piltdown man" was created to meet the expectations of the British archaeological community, and hence the fraud succeeded.

  12. Excavations at Schöningen and paradigm shifts in human evolution.

    Science.gov (United States)

    Conard, Nicholas J; Serangeli, Jordi; Böhner, Utz; Starkovich, Britt M; Miller, Christopher E; Urban, Brigitte; Van Kolfschoten, Thijs

    2015-12-01

    The exceptional preservation at Schöningen together with a mixture of perseverance, hard work, and sheer luck led to the recovery of unique finds in an exceptional context. The 1995 discovery of numerous wooden artifacts, most notably at least 10 carefully made spears together with the skeletons of at least 20 to 25 butchered horses, brought the debate about hunting versus scavenging among late archaic hominins and analogous arguments about the purportedly primitive behavior of Homo heidelbergensis and Neanderthals to an end. Work under H. Thieme's lead from 1992 to 2008 and results from the current team since 2008 demonstrate that late H. heidelbergensis or early Neanderthals used sophisticated artifacts made from floral and faunal materials, in addition to lithic artifacts more typically recovered at Lower Paleolithic sites. The finds from the famous Horse Butchery Site and two dozen other archaeological horizons from the edges of the open-cast mine at Schöningen provide many new insights into the technology and behavioral patterns of hominins about 300 ka BP during MIS 9 on the Northern European Plain. An analysis of the finds from Schöningen and their contexts shows that the inhabitants of the site were skilled hunters at the top of the food chain and exhibited a high level of planning depth. These hominins had command of effective means of communication about the here and now, and the past and the future, that allowed them to repeatedly execute well-coordinated and successful group activities that likely culminated in a division of labor and social and economic patterns radically different from those of all non-human primates. The unique preservation and high quality excavations have led to a major paradigm shift or "Schöningen Effect" that changed our views of human evolution during the late Lower Paleolithic. In this respect, we can view the behaviors documented at Schöningen as a plausible baseline for the behavioral sophistication of archaic hominins

  13. Role of Mitochondrial Complex IV in Age-Dependent Obesity

    Directory of Open Access Journals (Sweden)

    Ines Soro-Arnaiz

    2016-09-01

    Full Text Available Aging is associated with progressive white adipose tissue (WAT enlargement initiated early in life, but the molecular mechanisms involved remain unknown. Here we show that mitochondrial complex IV (CIV activity and assembly are already repressed in white adipocytes of middle-aged mice and involve a HIF1A-dependent decline of essential CIV components such as COX5B. At the molecular level, HIF1A binds to the Cox5b proximal promoter and represses its expression. Silencing of Cox5b decreased fatty acid oxidation and promoted intracellular lipid accumulation. Moreover, local in vivo Cox5b silencing in WAT of young mice increased the size of adipocytes, whereas restoration of COX5B expression in aging mice counteracted adipocyte enlargement. An age-dependent reduction in COX5B gene expression was also found in human visceral adipose tissue. Collectively, our findings establish a pivotal role for CIV dysfunction in progressive white adipocyte enlargement during aging, which can be restored to alleviate age-dependent WAT expansion.

  14. Challenge the science-stereotype. Der Einfluss von Technik-Freizeitkursen auf das Naturwissenschaften-Stereotyp von Schülerinnen und Schülern

    OpenAIRE

    Hannover, Bettina; Kessels, Ursula

    2002-01-01

    Der Aufsatz untersucht Aspekte von Kultur, die die individuelle Interessen- und Leistungsentwicklung von Schülerinnen und Schülern prägen ... . Es stehen die Kulturen spezifischer Schulfächer im Vordergrund. Im Aufsatz werden kulturell geteilte Annahmen über mathematisch- naturwissenschaftliche Schulfächer im Unterschied zu geistes- und sozialwissenschaftlichen Disziplinen untersucht; nämlich stereotype Vorstellungen über den Gegenstandsbereich, über Unterrichtsscripts, über typische Lehrpers...

  15. Iatrogenic Subclinical Hyperthyroidism Does Not Promote Weight Loss.

    Science.gov (United States)

    Kedia, Rohit; Lowes, Alicia; Gillis, Sarah; Markert, Ronald; Koroscil, Thomas

    2016-02-01

    Among patients who have undergone total thyroidectomy, do those with thyroid cancer being kept iatrogenically subclinical hyperthyroid (SCH) differ from euthyroid patients in long-term weight change? In a retrospective study, medical records identified 291 patients who had undergone a thyroidectomy for differentiated thyroid cancer or benign thyroid disease. Weight, thyroid-stimulating hormone, and levothyroxine dose were measured presurgery and 1, 2, and 3 years postsurgery. Of 291 patients, 147 were in the SCH group and 144 were in the euthyroid group. At all 3 years both groups gained weight from baseline, but the two groups did not differ in weight change from baseline at any time period: year 1 (SCH mean 0.4% ± 6.2% weight gain vs euthyroid group mean 2.2% ± 6.6% weight gain; P = 0.12), year 2 (SCH mean 1.1% ± 9.1% weight gain vs euthyroid mean 2.9% ± 7.8% weight gain; P = 0.22), and year 3 (SCH mean 2.6% ± 9.2% weight gain vs euthyroid mean 3.1% ± 11.1% weight gain; P = 0.49). Among total thyroidectomy patients, weight change did not differ between SCH patients and euthyroid patients at years 1 through 3. As such, the use of levothyroxine to induce SCH did not lead to long-term weight change when compared with euthyroid patients.

  16. Deriving a cardiac ageing signature to reveal MMP-9-dependent inflammatory signalling in senescence.

    Science.gov (United States)

    Ma, Yonggang; Chiao, Ying Ann; Clark, Ryan; Flynn, Elizabeth R; Yabluchanskiy, Andriy; Ghasemi, Omid; Zouein, Fouad; Lindsey, Merry L; Jin, Yu-Fang

    2015-06-01

    Cardiac ageing involves the progressive development of cardiac fibrosis and diastolic dysfunction coordinated by MMP-9. Here, we report a cardiac ageing signature that encompasses macrophage pro-inflammatory signalling in the left ventricle (LV) and distinguishes biological from chronological ageing. Young (6-9 months), middle-aged (12-15 months), old (18-24 months), and senescent (26-34 months) mice of both C57BL/6J wild type (WT) and MMP-9 null were evaluated. Using an identified inflammatory pattern, we were able to define individual mice based on their biological, rather than chronological, age. Bcl6, Ccl24, and Il4 were the strongest inflammatory markers of the cardiac ageing signature. The decline in early-to-late LV filling ratio was most strongly predicted by Bcl6, Il1r1, Ccl24, Crp, and Cxcl13 patterns, whereas LV wall thickness was most predicted by Abcf1, Tollip, Scye1, and Mif patterns. With age, there was a linear increase in cardiac M1 macrophages and a decrease in cardiac M2 macrophages in WT mice; of which, both were prevented by MMP-9 deletion. In vitro, MMP-9 directly activated young macrophage polarization to an M1/M2 mid-transition state. Our results define the cardiac ageing inflammatory signature and assign MMP-9 roles in mediating the inflammaging profile by indirectly and directly modifying macrophage polarization. Our results explain early mechanisms that stimulate ageing-induced cardiac fibrosis and diastolic dysfunction. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  17. Aufbau von regionalen Schülerforschungszentren Berichte und Praxisempfehlungen

    CERN Document Server

    Bayatloo, Annabel

    2013-01-01

    Angesichts des sich verschärfenden Fachkräftemangels ist es wichtig, die vorhandenen Begabungspotenziale noch wirkungsvoller zu identifizieren und auszuschöpfen. Vor allem im Bereich von Mathematik, Informatik, Naturwissenschaft und Technik (MINT) erweist es sich als zielführend, künftig stärker auf forschendes Lernen zu setzen. Dieser pädagogische Ansatz wird auf vorbildliche Weise an Schülerforschungszentren verwirklicht. Aufgrund der Chancen für die Nachwuchsförderung, die mit diesen außerschulischen MINT-Bildungszentren verbunden sind, haben der Deutsche Industrie- und Handelskammertag (DIHK), die IHK Darmstadt, LernortLabor - Bundesverband der Schülerlabore e. V. und die Stiftung Jugend forscht e. V. gemeinsam einen Leitfaden für den „Aufbau regionaler Schülerforschungszentren“ erarbeitet. Die neue Publikation ist als Best Practice-Handreichung konzipiert und soll vor allem regionale Entscheidungsträger in die Lage versetzen, auf diesem Feld selbst aktiv zu werden und den begonnenen Pr...

  18. Das verfügbare Geld im Jugendalltag von 13- bis 17-jährigen Schülern und Schülerinnen: empirische Ergebnisse

    OpenAIRE

    Tully, Claus; Santen, Eric van

    2012-01-01

    "Prozesse der Bildung, Ablösung, Differenzierung und Positionierung gehören zur Verselbstständigung und zum Erwachsenwerden. Die Verfügung über Geld spielt dabei eine wichtige Rolle. Geld, als Voraussetzung für Konsum und damit Mittel, um 'im Spiel zu bleiben'. SchülerInnen verfügen über keine eigenen Einkünfte und sind auf Zuwendungen (Taschengeld und staatliche Transferleistungen wie Schüler-Bafög) oder selbst hinzu verdientes Geld angewiesen. Der Beitrag stellt empirische Ergebnisse zur Hö...

  19. The H+/K+ ATPase Inhibitor SCH-28080 Inhibits Insulin Secretion and Induces Cell Death in INS-1E Rat Insulinoma Cells

    Directory of Open Access Journals (Sweden)

    Martin Jakab

    2017-10-01

    was unaffected. The L-type ICav blocker nifedipine caused a full inhibition of GSIS at 10 and 20 µM. At 20 µM, SCH-28080 inhibited ICav comparable to 20 µM nifedipine and in addition augmented IKATP recorded at -60 mV and hyperpolarized Vmem by ∼15 mV. Cell viability 2 and 24 h post treatment with SCH-28080 was dose-dependently inhibited with IC50 values of 22.9 µM and 15.3 µM, respectively. At 20 µM the percentages of Annexin-V+, caspase+ and propidium iodide+ cells were significantly increased after 24 and 48 h. Concurrently, the MCV was significantly decreased (apoptotic volume decrease, AVD and the SSC signal was increased. At concentrations >40–50 µM, SCH-28080 became progressively cytotoxic causing a steep increase in necrotic cells already 2 h post treatment and a breakdown of ΔΨm within 4 h under 50 and 100 µM while 10 and 20 µM had no effect on ΔΨm within 24 h. Conclusion: We demonstrate expression of HKα2 in rat INS-1E cells. However, the pump is apparently non-functional under the given conditions. Nonetheless the H+/K+ ATPase blocker SCH-28080 inhibits insulin secretion and induces cell death. Importantly, we show that SCH-28080 inhibits ICav - and activates KATP channels identifying them as novel “off-targets” of the inhibitor, causing hyperpolarization of Vmem and inhibition of insulin secretion.

  20. ATM regulates NF-κB-dependent immediate-early genes via RelA Ser 276 phosphorylation coupled to CDK9 promoter recruitment

    Science.gov (United States)

    Fang, Ling; Choudhary, Sanjeev; Zhao, Yingxin; Edeh, Chukwudi B; Yang, Chunying; Boldogh, Istvan; Brasier, Allan R.

    2014-01-01

    Ataxia-telangiectasia mutated (ATM), a member of the phosphatidylinositol 3 kinase-like kinase family, is a master regulator of the double strand DNA break-repair pathway after genotoxic stress. Here, we found ATM serves as an essential regulator of TNF-induced NF-kB pathway. We observed that TNF exposure of cells rapidly induced DNA double strand breaks and activates ATM. TNF-induced ROS promote nuclear IKKγ association with ubiquitin and its complex formation with ATM for nuclear export. Activated cytoplasmic ATM is involved in the selective recruitment of the E3-ubiquitin ligase β-TrCP to phospho-IκBα proteosomal degradation. Importantly, ATM binds and activates the catalytic subunit of protein kinase A (PKAc), ribosmal S6 kinase that controls RelA Ser 276 phosphorylation. In ATM knockdown cells, TNF-induced RelA Ser 276 phosphorylation is significantly decreased. We further observed decreased binding and recruitment of the transcriptional elongation complex containing cyclin dependent kinase-9 (CDK9; a kinase necessary for triggering transcriptional elongation) to promoters of NF-κB-dependent immediate-early cytokine genes, in ATM knockdown cells. We conclude that ATM is a nuclear damage-response signal modulator of TNF-induced NF-κB activation that plays a key scaffolding role in IκBα degradation and RelA Ser 276 phosphorylation. Our study provides a mechanistic explanation of decreased innate immune response associated with A-T mutation. PMID:24957606

  1. Changes in the MEG background activity in patients with positive symptoms of schizophrenia: spectral analysis and impact of age

    International Nuclear Information System (INIS)

    Escudero, Javier; Ifeachor, Emmanuel; Fernández, Alberto; López-Ibor, Juan José; Hornero, Roberto

    2013-01-01

    The frequency spectrum of the magnetoencephalogram (MEG) background activity was analysed in 15 schizophrenia (SCH) patients with predominant positive symptoms and 17 age-matched healthy control subjects using the following variables: median frequency (MF), spectral entropy (SpecEn) and relative power in delta (RPδ), theta (RPθ), lower alpha (RPα1), upper alpha (RPα2), beta (RPβ) and gamma (RPγ) bands. We found significant differences between the two subject groups in the average level of MF and RPγ in some regions of the scalp. Additionally, the MF, SpecEn, RPβ and RPγ values of SCH patients with positive symptoms had a different dependence on age as compared with the results of control subjects, suggesting that SCH affects the way in which the brain activity evolves with age. Moreover, we also classified the MEG signals by means of a cross-validated feature selection process followed by a logistic regression. The subjects were classified with 71.3% accuracy and an area under the ROC curve of 0.741. Thus, the spectral and classification analysis of the MEG in SCH may provide insights into how this condition affects the brain activity and may help in its early detection. (paper)

  2. Die Schönbuchbahn. Von der Nebenbahn zum S-Bahn-Standard

    Science.gov (United States)

    Brauer, Tobias

    2017-09-01

    Since the successful reactivation of the schönbuch railway between Böblingen and Dettenhausen the number of passengers has increased continuously. Due to this high demand of over 8000 people per day and the increase of popularity the current expansion projects include the electrification of the 17 km long track and the installation of double-track sections for providing a 15-minute-service between Böblingen and Holzgerlingen. To realize the new operational concept, Zweckverband Schönbuchbahn (ZVS), the public transport authority, has ordered nine light rail-styled vehicles (with costs around 51,3 mio. euro for developing and construction). In this way the schönbuch railway is an important factor to guarantee a sustainable and forward-looking mobility in the metropolitan area of Stuttgart and for restricting car traffic.

  3. Comparison between dopamine-stimulated adenylate cyclase and 3H-SCH 23390 binding in rat striatum

    International Nuclear Information System (INIS)

    Andersen, P.H.; Groenvald, F.C.; Jansen, J.A.

    1985-01-01

    Methods for measuring 3 H-SCH 23990 binding and dopamine (DA) stimulated adenylate cyclase (AC) were established in identical tissue preparations and under similar experimental conditions. Pharmacological characterization revealed that both assays involved interaction with the D1 receptor or closely associated sites. In order to investigate whether the binding sites for 3 H-SCH 23390 and DA in fact are identical, the antagonistic effects of a variety of pharmacologically active compounds were examined. Surprisingly, the K/sub i/-values obtained from Schild-plot analysis of the antagonism of DA-stimulated AC, were 80-240 times higher than the K/sub i/-values obtained from competition curves of 3 H-SCH 23390 binding. Since both assays were performed under identical conditions, the differences in K/sub i/-values indicate the possibility of different binding sites for DA and 3 H-SCH 23390 or, that DA and 3 -SCH 23390 label different states of the same receptor. 19 references, 7 figures, 2 tables

  4. [Henoch-Schönlein purpura in the adult].

    Science.gov (United States)

    Pillebout, E; Verine, J

    2014-06-01

    Henoch-Schönlein purpura is a systemic vasculitis of the small vessels characterized by perivascular leucocyte infiltrates. It is an immunoglobulin A-related immune complex-mediated disease involving the skin, the joints and the gastrointestinal system. Renal disease may sometimes be associated to these clinical manifestations. Prevalence of the nephritis is highly variable, depending on the series. More rarely, other organs such as the lungs, the heart or the nervous system may be involved. The clinical diagnosis is confirmed by histopathology of the skin (leukocytoclastic vasculitis) and kidney (endo-capillary proliferative glomerulonephritis), showing IgA deposits in these tissues. Short-term prognosis depends on the severity of digestive involvement, but long-term prognosis depends on the renal disease. Recent publications of pediatric and adult series show that the chronic renal failure may progress, sometimes more than ten years after the initial flare. Treatment is usually supportive. The benefit of more specific treatments (corticosteroids or immunosuppressive drugs) in severe visceral forms (usually abdominal or kidney) has not yet been established. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  5. Efficacy of SCH27899 in an Animal Model of Legionnaires' Disease Using Immunocompromised A/J Mice

    Science.gov (United States)

    Brieland, Joan K.; Loebenberg, David; Menzel, Fred; Hare, Roberta S.

    2000-01-01

    The efficacy of SCH27899, a new everninomicin antibiotic, against replicative Legionella pneumophila lung infections in an immunocompromised host was evaluated using a murine model of Legionnaires' disease. A/J mice were immunocompromised with cortisone acetate and inoculated intratracheally with L. pneumophila serogroup 1 (105 CFU per mouse). At 24 h postinoculation, mice were administered either SCH27899 (6 to 60 mg/kg [MPK] intravenously) or a placebo once daily for 5 days, and mortality and intrapulmonary growth of L. pneumophila were assessed. In the absence of SCH27899, there was 100% mortality in L. pneumophila-infected mice, with exponential intrapulmonary growth of the bacteria. In contrast, administration of SCH27899 at a dose of ≥30 MPK resulted in ≥90% survival of infected mice, which was associated with inhibition of intrapulmonary growth of L. pneumophila. In subsequent studies, the efficacy of SCH27899 was compared to ofloxacin (OFX) and azithromycin (AZI). Administration of SCH27899, OFX, or AZI at a dose of ≥30 MPK once daily for 5 days resulted in ≥85% survival of infected mice and inhibition of intrapulmonary growth of the bacteria. However, L. pneumophila CFU were recovered in lung homogenates following cessation of therapy with all three antibiotics. These studies demonstrate that SCH27899 effectively prevents fatal replicative L. pneumophila lung infection in immunocompromised A/J mice by inhibition of intrapulmonary growth of the bacteria. However, in this murine model of pulmonary legionellosis, SCH27899, like OFX and AZI, was bacteriostatic. PMID:10770771

  6. New family of lanthanide-based inorganic-organic hybrid frameworks: Ln2(OH)4[O3S(CH2)nSO3]·2H2O (Ln = La, Ce, Pr, Nd, Sm; n = 3, 4) and their derivatives.

    Science.gov (United States)

    Liang, Jianbo; Ma, Renzhi; Ebina, Yasuo; Geng, Fengxia; Sasaki, Takayoshi

    2013-02-18

    We report the synthesis and structure characterization of a new family of lanthanide-based inorganic-organic hybrid frameworks, Ln(2)(OH)(4)[O(3)S(CH(2))(n)SO(3)]·2H(2)O (Ln = La, Ce, Pr, Nd, Sm; n = 3, 4), and their oxide derivatives. Highly crystallized samples were synthesized by homogeneous precipitation of Ln(3+) ions from a solution containing α,ω-organodisulfonate salts promoted by slow hydrolysis of hexamethylenetetramine. The crystal structure solved from powder X-ray diffraction data revealed that this material comprises two-dimensional cationic lanthanide hydroxide {[Ln(OH)(2)(H(2)O)](+)}(∞) layers, which are cross-linked by α,ω-organodisulfonate ligands into a three-dimensional pillared framework. This hybrid framework can be regarded as a derivative of UCl(3)-type Ln(OH)(3) involving penetration of organic chains into two {LnO(9)} polyhedra. Substitutional modification of the lanthanide coordination promotes a 2D arrangement of the {LnO(9)} polyhedra. A new hybrid oxide, Ln(2)O(2)[O(3)S(CH(2))(n)SO(3)], which is supposed to consist of alternating {[Ln(2)O(2)](2+)}(∞) layers and α,ω-organodisulfonate ligands, can be derived from the hydroxide form upon dehydration/dehydroxylation. These hybrid frameworks provide new opportunities to engineer the interlayer chemistry of layered structures and achieve advanced functionalities coupled with the advantages of lanthanide elements.

  7. Design limits for HT9 cladding using stress-induced aging data

    International Nuclear Information System (INIS)

    Fox, G.L.

    1986-04-01

    Stress-temperature design guidelines are developed for the ferritic/martensitic cladding material HT9. High temperature operation for HT9 may cause microstructural changes/aging which softens the structure and causes increased creep rates. Higher creep strains means cladding breech becomes more probable before the end of the expected pin lifetime. Tertiary creep is considered an indication of microstructural changes and is to be avoided in fuel pin operation. The creep rate correlation, which includes tertiary creep, is examined for information on stress-temperature relationships which promote aging. This approach leads to design limits for HT9 which are compared with expected hot channel conditions for fuel pins in the Core Demonstration Experiment (CDE) planned for FFTF. The results show aging should not be significant for CDE

  8. SchNet - A deep learning architecture for molecules and materials

    Science.gov (United States)

    Schütt, K. T.; Sauceda, H. E.; Kindermans, P.-J.; Tkatchenko, A.; Müller, K.-R.

    2018-06-01

    Deep learning has led to a paradigm shift in artificial intelligence, including web, text, and image search, speech recognition, as well as bioinformatics, with growing impact in chemical physics. Machine learning, in general, and deep learning, in particular, are ideally suitable for representing quantum-mechanical interactions, enabling us to model nonlinear potential-energy surfaces or enhancing the exploration of chemical compound space. Here we present the deep learning architecture SchNet that is specifically designed to model atomistic systems by making use of continuous-filter convolutional layers. We demonstrate the capabilities of SchNet by accurately predicting a range of properties across chemical space for molecules and materials, where our model learns chemically plausible embeddings of atom types across the periodic table. Finally, we employ SchNet to predict potential-energy surfaces and energy-conserving force fields for molecular dynamics simulations of small molecules and perform an exemplary study on the quantum-mechanical properties of C20-fullerene that would have been infeasible with regular ab initio molecular dynamics.

  9. Schéma directeur des Systèmes d'information 2012-2016

    OpenAIRE

    Institut National de Recherche Agronomique UAR 0776 Administration du siège

    2012-01-01

    Le schéma directeur des systèmes d’information de l’inra est le premier Schéma directeur dont l’institut se dote dans le champ des systèmes D’information. Il couvre la période 2012‐2016 du contrat d’objectifs Et s’inscrit dans les perspectives scientifiques dressées par le document D’orientation 2010‐2020

  10. Homicide by Sch from a syringe-like dart ejected by a compound crossbow.

    Science.gov (United States)

    Guo, Wei; Luo, Guochang; Wang, Hao; Meng, Xiangzhi

    2015-02-01

    The compound crossbow can be used to eject syringe-like dart loaded with poisonous solution. Succinylcholine (Sch) is a short-acting neuromuscular blocker medically used to achieve complete relaxation of muscle for a good intubation condition. Without the help of an artificial respirator, intramuscular injection of a large dose of Sch can paralyze the respiratory muscle and result in the receiver's death. In this paper, we present the homicide case of a young male killed by Sch from a syringe-like dart ejected by a compound crossbow. The subcutaneous and muscular hemorrhages observed around the entry were more severe than that caused by a medical injection. Additionally, other autopsy results showed the external appearance of a pinhole, general asphyxia signs and pathological findings which were not characteristic. The discovery of a syringe-like dart at the scene is the critical clue and reason for analyzing for Sch, which is commonly used to load syringe-like dart to paralyze and steal dog in the countryside of China. Copyright © 2014 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  11. Neurodevelopmental Versus Neurodegenerative Model of Schizophrenia and Bipolar Disorder: Comparison with Physiological Brain Development and Aging.

    Science.gov (United States)

    Buoli, Massimiliano; Serati, Marta; Caldiroli, Alice; Cremaschi, Laura; Altamura, Alfredo Carlo

    2017-03-01

    Available data support a contribution of both neurodevelopmental and neurodegenerative factors in the etiology of schizophrenia (SCH) and bipolar disorder (BD). Of note, one of the most important issue of the current psychiatric research is to identify the specific factors that contribute to impaired brain development and neurodegeneration in SCH and BD, and especially how these factors alter normal brain development and physiological aging process. Our hypothesis is that only specific damages, taking place in precise brain development stages, are associated with future SCH /BD onset and that neurodegeneration consists of an acceleration of brain aging after SCH /BD onset. In support of our hypothesis, the results of the present narrative mini-review shows as neurodevelopmental damages generally contribute to neuropsychiatric syndromes (e.g. hypothyroidism or treponema pallidum), but only some of them are specifically associated with adult SCH and BD (e.g. toxoplasma or substance abuse), particularly if they happen in specific stages of brain development. On the other hand, cognitive impairment and brain changes, associated with long duration of SCH /BD, look like what happens during aging: memory, executive domains and prefrontal cortex are implicated both in aging and in SCH /BD progression. Future research will explore possible validity of this etiological model for SCH and BD.

  12. Henoch-Schönlein purpura with intracerebral haemorrhage in an adult patient: a case report

    Directory of Open Access Journals (Sweden)

    Karamadoukis Lazarus

    2008-06-01

    Full Text Available Abstract Introduction Henoch-Schönlein purpura is a small vessel vasculitis that affects mainly the skin, joints, gastrointestinal tract and kidneys. The central nervous system is also occasionally affected, although the majority of patients experience only mild symptoms such as headaches and behavioural changes. Intracerebral haemorrhage is a rare complication of Henoch-Schönlein purpura that so far has mainly been described in children and young adolescence. Case presentation We describe a 42-year-old man with Henoch-Schönlein purpura who developed an acute intracerebral haemorrhage that coincided with a reactivation of his vasculitis and the development of renal failure following discontinuation of steroids. In this patient, both the Henoch-Schönlein purpura and his neurological symptoms were successfully treated with intravenous cyclophosphamide and methylprednisolone, followed by a short course of oral cyclophosphamide and long-term oral prednisolone. His renal function also recovered sufficiently not to require renal replacement therapy. Conclusion The management of Henoch-Schönlein nephritis remains unclear, especially in the presence of severe complications such as intracerebral haemorrhage. We describe a successful outcome in such a patient.

  13. Health Promotion Behaviors and Chronic Diseases of Aging in the Elderly People of Iranshahr*- IR Iran.

    Science.gov (United States)

    Pishkar Mofrad, Zahra; Jahantigh, Mozhgan; Arbabisarjou, Azizollah

    2015-07-13

    Aging is considered as the phenomenon of the day in the health arena of the world and Iran. It is anticipated that there will be an explosion of aging population in Iran in about 2031 and 20-25% of the population will be aged over 60 years. With aging, chronic diseases also increase and diminish the functional ability of older people. On the other hand, increased healthcare costs should be also added to this issue. Health promotion is a concept of process that continues throughout life. As much as health promotion is important in children and adults, it is equally important in older people. In fact, the elderlies, as a group, also acquire many benefits from health promotion behaviors. Due to the increasing elderly population, geriatric health promotion and enhancing the health level of older people is proposed as a health priority that should be properly planned. Hence, the present study has been conducted in this regard and aims to identify behaviors of health promotion and chronic diseases of aging in the elderly people of Iranshahr-Iran. The present research is a cross-sectional descriptive study whose population consists of 425 elderly people aged 60 years and over, who lived in the city of Iranshahr*, IR Iran. The random cluster sampling method has been used to select the research samples. The required information was collected using a questionnaire which was distributed among the older people through visiting their homes; then, the collected data was statistically analyzed using the statistical software of SPSS version 13. the research findings show that the mean age of older people is and the highest frequency belongs to the age group of 60 years and the maximum age is 92 years. 69.5% of the older people were in the age group of the young elderly (60-69 years) and 44% of them lived with their married children; also 55.8%, 81.9%, 70.5%, and 74.4% of them were respectively female, illiterate, married, and unemployed. The mean score of geriatric health

  14. The Creative Side of the Reflective Planner. Updating the Schön’s Findings

    Directory of Open Access Journals (Sweden)

    Maria Rosaria Stufano Melone

    2014-05-01

    Full Text Available The self-reflection on their own work has always been present in all designers, including architects and planners. In the mid 80-90 Donald Schön has made more explicit this aspect, which until then had not found a systematic scientific treatment.  The results of Schön are the basis of practical planning of the 90s period. However, the Schön's analysis reveals a context of knowledge of mental functioning typical of the conceiving period. From the 90s until now numerous advances in knowledge of the mechanisms of rationality, reflection and creativity have been made, and in this context we are interested in the progress made in the field of creativity.  We try to integrate and update the Schön's reflection with the new available theories such as the CK theory to offer planners a more innovated range of tools in order to understand and make better use of their creativity and self-reflection about their own creativity.

  15. Covalent Modifications of Histone H3K9 Promote Binding of CHD3

    Directory of Open Access Journals (Sweden)

    Adam H. Tencer

    2017-10-01

    Full Text Available Chromatin remodeling is required for genome function and is facilitated by ATP-dependent complexes, such as nucleosome remodeling and deacetylase (NuRD. Among its core components is the chromodomain helicase DNA binding protein 3 (CHD3 whose functional significance is not well established. Here, we show that CHD3 co-localizes with the other NuRD subunits, including HDAC1, near the H3K9ac-enriched promoters of the NuRD target genes. The tandem PHD fingers of CHD3 bind histone H3 tails and posttranslational modifications that increase hydrophobicity of H3K9—methylation or acetylation (H3K9me3 or H3K9ac—enhance this interaction. Binding of CHD3 PHDs promotes H3K9Cme3-nucleosome unwrapping in vitro and perturbs the pericentric heterochromatin structure in vivo. Methylation or acetylation of H3K9 uniquely alleviates the intra-nucleosomal interaction of histone H3 tails, increasing H3K9 accessibility. Collectively, our data suggest that the targeting of covalently modified H3K9 by CHD3 might be essential in diverse functions of NuRD.

  16. Protective effect of caffeine and a selective A2A receptor antagonist on impairment of memory and oxidative stress of aged rats.

    Science.gov (United States)

    Leite, Marlon Régis; Wilhelm, Ethel A; Jesse, Cristiano R; Brandão, Ricardo; Nogueira, Cristina Wayne

    2011-04-01

    In this study, the effects of caffeine (CAF) and SCH58261, a selective A(2A) receptor antagonist, on memory impairment and oxidative stress generated by aging in rats were investigated. Young and aged rats were treated daily per 10 days with CAF (30 mg/kg p.o.) or SCH58261 (0.5mg/kg, p.o.) or vehicle (1 ml/kg p.o.). Rats were trained and tested in a novel object recognition task. After the behavioral test, ascorbic acid and oxygen and nitrogen reactive species levels as well as Na(+)K(+) ATPase activity were determined in rat brain. The results demonstrated that the age-related memory deficit was reversed by treatment with CAF or SCH58261. Treatment with CAF or SCH58261 significantly normalized oxygen and nitrogen reactive species levels increased in brains of aged rats. Na(+)K(+) ATPase activity inhibited in brains of aged rats was also normalized by CAF or SCH58261 treatment. A decrease in basal ascorbic acid levels in brains of aged rats was not changed by CAF or SCH58261. These results demonstrated that CAF and SCH58261, modulators of adenosinergic receptors, were able to reverse age-associated memory impairment and to partially reduce oxidative stress. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. Raamatuautomaadid Hamburgis / A. Bösch ; refereerinud Lea Laurberg-Heckelmann

    Index Scriptorium Estoniae

    Bösch, A.

    2012-01-01

    Refereeritud väljaandest: Bösch, A. Eine Schachtel Literatur ziehen: Bettina von Bülow betreibt in Hamburg Bücherautomaten - Das Angebot reicht vom Comics bis zum Stadtführer. - Lübecker Nachrichten, 30./31.10.2011, lk. 19

  18. TLR9 ligation in pancreatic stellate cells promotes tumorigenesis.

    Science.gov (United States)

    Zambirinis, Constantinos P; Levie, Elliot; Nguy, Susanna; Avanzi, Antonina; Barilla, Rocky; Xu, Yijie; Seifert, Lena; Daley, Donnele; Greco, Stephanie H; Deutsch, Michael; Jonnadula, Saikiran; Torres-Hernandez, Alejandro; Tippens, Daniel; Pushalkar, Smruti; Eisenthal, Andrew; Saxena, Deepak; Ahn, Jiyoung; Hajdu, Cristina; Engle, Dannielle D; Tuveson, David; Miller, George

    2015-11-16

    Modulation of Toll-like receptor (TLR) signaling can have protective or protumorigenic effects on oncogenesis depending on the cancer subtype and on specific inflammatory elements within the tumor milieu. We found that TLR9 is widely expressed early during the course of pancreatic transformation and that TLR9 ligands are ubiquitous within the tumor microenvironment. TLR9 ligation markedly accelerates oncogenesis, whereas TLR9 deletion is protective. We show that TLR9 activation has distinct effects on the epithelial, inflammatory, and fibrogenic cellular subsets in pancreatic carcinoma and plays a central role in cross talk between these compartments. Specifically, TLR9 activation can induce proinflammatory signaling in transformed epithelial cells, but does not elicit oncogene expression or cancer cell proliferation. Conversely, TLR9 ligation induces pancreatic stellate cells (PSCs) to become fibrogenic and secrete chemokines that promote epithelial cell proliferation. TLR9-activated PSCs mediate their protumorigenic effects on the epithelial compartment via CCL11. Additionally, TLR9 has immune-suppressive effects in the tumor microenvironment (TME) via induction of regulatory T cell recruitment and myeloid-derived suppressor cell proliferation. Collectively, our work shows that TLR9 has protumorigenic effects in pancreatic carcinoma which are distinct from its influence in extrapancreatic malignancies and from the mechanistic effects of other TLRs on pancreatic oncogenesis. © 2015 Zambirinis et al.

  19. Die Universitätsbibliothek für Schüler - Angebote der UB Würzburg

    OpenAIRE

    Hämmer, Viola; Südekum, Karl

    2011-01-01

    Mit Einführungsveranstaltungen für Schüler, individueller Beratung bei der Recherche und einem eigenen Bereich auf der Homepage unterstützt die Universitätsbibliothek Würzburg Schüler bei ihren ersten wissenschaftlichen Arbeiten. Damit soll auch eine Brücke geschlagen werden zwischen den Bildungsinstitutionen Schule und Hochschule.

  20. The FOX transcription factor Hcm1 regulates oxidative metabolism in response to early nutrient limitation in yeast. Role of Snf1 and Tor1/Sch9 kinases.

    Science.gov (United States)

    Rodríguez-Colman, María José; Sorolla, M Alba; Vall-Llaura, Núria; Tamarit, Jordi; Ros, Joaquim; Cabiscol, Elisa

    2013-08-01

    Within Saccharomyces cerevisiae, Hcm1is a member of the forkhead transcription factor family with a role in chromosome organization. Our group recently described its involvement in mitochondrial biogenesis and stress resistance, and reports here that Hcm1 played a role in adaptation to respiratory metabolism when glucose or nitrogen was decreased. Regulation of Hcm1 activity occurs in at least three ways: i) protein quantity, ii) subcellular localization, and iii) transcriptional activity. Transcriptional activity was measured using a reporter gene fused to a promoter that contains a binding site for Hcm1. We also analyzed the levels of several genes whose expression is known to be regulated by Hcm1 levels and the role of the main kinases known to respond to nutrients. Lack of sucrose-nonfermenting (Snf1) kinase increases cytoplasmic localization of Hcm1, whereas Δtor1 cells showed a mild increase in nuclear Hcm1. In vitro experiments showed that Snf1 clearly phosphorylates Hcm1 while Sch9 exerts a milder phosphorylation. Although in vitroTor1 does not directly phosphorylate Hcm1, in vivo rapamycin treatment increases nuclear Hcm1. We conclude that Hcm1 participates in the adaptation of cells from fermentation to respiratory metabolism during nutrient scarcity. According to our hypothesis, when nutrient levels decrease, Snf1 phosphorylates Hcm1. This results in a shift from the cytoplasm to the nucleus and increased transcriptional activity of genes involved in respiration, use of alternative energy sources, NAD synthesis and oxidative stress resistance. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Risk evaluations of aging: Procedures guide for an age-dependent PSA with emphasis on prioritization and sensitivity studies

    International Nuclear Information System (INIS)

    Vesely, W.E.

    1991-01-01

    Based on the previous work which has been performed in the project, a procedures guide is being developed for carrying out an age-dependent probabilistic safety assessment (PSA) for evaluating the core damage frequency with aging effects explicitly treated. A PSA is basically a Level 1 Probabilistic Risk Assessment (PRA). The emphasis of the guide is on prioritization and sensitivity studies. Focus is also on active components although consideration of aging effects in passive components is also treated. The guide is intended to become a NUREG/CR and is the first of three volumes which are being developed. The following topics with demonstrations and applications are described in the presentation: (1) the age-dependent PSA versus the standard PSA; (2) component reliability models used in an age-dependent PSA; (3) approaches for transforming a PSA into an age-dependent PSA; (4) application of an age-dependent PSA; (5) using a PSA to evaluate the risk effects from aging passive components; (6) evaluation of the risk importance of passive components; (7) prioritizations of aging contributors; (8) evaluations of test and maintenance effectiveness; and (9) sensitivity studies and uncertainty analyses of aging effects

  2. Impact of radiobiological considerations on epidemiological inferences of age-dependent radiosensitivity

    International Nuclear Information System (INIS)

    Crawford-Brown, D.J.

    1983-01-01

    Current epidemiological studies of the age-dependent risk of radiogenic carcinomas are based on populations still in the early stages of cancer expression. The result is a set of logical uncertainties concerning the manner in which inferences may be drawn from the existing data. These uncertainties may be formalized and examined through the application of various radiobiological principles developed from more fundamental experimental data. Chief amongst these considerations are the time course of tumor expression, the role of relative and absolute risk models, the distribution of effects between initiation and promotion, the age-dependent fraction of time a critical cell remains in radiosensitive stages and the combinatorics of the critical cellular subpopulations. Each of these and the combinatorics of the critical cellular subpopulations. Each of these principles are examined in light of their impact on the structuring of epidemiologic data and the drawing of inferences concerning age-dependent radiogenic risk. The data on atomic bomb survivors are employed as a relevant example

  3. Transcriptional Inhibition of Matrix Metal loproteinase 9 (MMP-9 Activity by a c-fos/Estrogen Receptor Fusion Protein is Mediated by the Proximal AP-1 Site of the MMP-9 Promoter and Correlates with Reduced Tumor Cell Invasion

    Directory of Open Access Journals (Sweden)

    David L. Crowe

    1999-10-01

    Full Text Available Tumor cell invasion of basement membranes is one of the hallmarks of malignant transformation. Tumor cells secrete proteolytic enzymes known as matrix metalloproteinases (MMPs which degrade extracellular matrix molecules. Increased expression of MMP-9 has been associated with acquisition of invasive phenotype in many tumors. However, multiple mechanisms for regulation of MMP-9 gene expression by tumor cell lines have been proposed. A number of transcription factor binding sites have been characterized in the upstream regulatory region of the MMP-9 gene, including those for AP-1. To determine how a specific AP-1 family member, c-fos, regulates MMP-9 promoter activity through these sites, we used an expression vector containing the c-fos coding region fused to the estrogen receptor (ER ligand binding domain. This construct is activated upon binding estradiol. Stable expression of this construct in ER negative squamous cell carcinoma (SCC lines produced an estradiol dependent decrease in the number of cells that migrated through a reconstituted basement membrane. This decreased invasiveness was accompanied by estradiol dependent downregulation of MMP-9 activity as determined by gelatin zymography. Estradiol also produced transcriptional downregulation of an MMP-9 promoter construct in cells transiently transfected with the c-fosER expression vector. This downregulation was mediated by the AP-1 site at —79 by in the MMP-9 promoter. We concluded that the proximal AP-1 site mediated the transcriptional downregulation of the MMP-9 promoter by a conditionally activated c-fos fusion protein.

  4. Henoch-Schönlein purpura in an older man presenting as rectal bleeding and IgA mesangioproliferative glomerulonephritis: a case report.

    Science.gov (United States)

    Cheungpasitporn, Wisit; Jirajariyavej, Teeranun; Howarth, Charles B; Rosen, Raquel M

    2011-08-10

    systemic steroid therapy. A history of diverticulosis can mislead physicians to the diagnosis of diverticular bleeding which is more common in this age group. The clinical manifestations of the disease, including characteristic skin rash, abdominal pain, joint inflammation and renal involvement raised the suspicious of Henoch-Schönlein purpura.

  5. Assessment of schistosomiasis and soil-transmitted helminths prevalence in school-aged children and opportunities for integration of control in local health services in Kwilu Province, the Democratic Republic of the Congo.

    Science.gov (United States)

    Inocencio da Luz, R; Linsuke, S; Lutumba, P; Hasker, E; Boelaert, M

    2017-11-01

    To determine the prevalence of schistosomiasis (SCH) and soil-transmitted helminths (STH) in the Democratic Republic of Congo, and to assess the capacity of the local health centres for diagnosis and treatment. Cross-sectional school-based survey in two health districts in the Province of Kwilu. We collected a stool and a urine sample for parasitological examination. Urine filtration and duplicate Kato-Katz thick smears were used for the diagnosis of SCH. Health centres were evaluated using a structured questionnaire. In total, 526 children participated in the study and the overall prevalence of Schistosoma mansoni infection was 8.9% (95% CI: 3.5-13.2) in both districts. The prevalence was higher in Mosango (11.7%; 95% CI: 8.9-14.8) than Yasa Bonga district (6.2%; 95% CI: 1.1-11.4). Urine filtration showed that Schistosoma haematobium infection was not present. The combined STH infection prevalence was 58.1% in both districts; hookworm infection was the most common STH found in 52.9% (95% CI: 29.3-62.4) of subjects, followed by Ascaris lumbricoides 9.3% (95% CI: 5.8-15.5) and Trichuris trichiura 2.1% (95% CI: 0.9-4.9). Mixed STH infections were observed as well as SCH-STH coinfection. Further mapping of both SCH and STH burden is needed, and coverage of preventive chemotherapy in school-aged children should be increased. © 2017 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

  6. Schéma équivalent petit signal d\\'un transistor à effet de champ à ...

    African Journals Online (AJOL)

    Dans cet article, les auteurs présentent un schéma équivalent petit signal d\\'un transistor à effet de champ à base de nano tube de carbone (CNTFETs). Les éléments du schéma équivalent sont obtenus à partir de la mesure des paramètres « scattering » S du CNTFETs pour un point de polarisation dans une gamme de ...

  7. Novel hydrated graphene ribbon unexpectedly promotes aged seed germination and root differentiation

    Science.gov (United States)

    Hu, Xiangang; Zhou, Qixing

    2014-01-01

    It is well known that graphene (G) induces nanotoxicity towards living organisms. Here, a novel and biocompatible hydrated graphene ribbon (HGR) unexpectedly promoted aged (two years) seed germination. HGR formed at the normal temperature and pressure (120 days hydration), presented 17.1% oxygen, 0.9% nitrogen groups, disorder-layer structure, with 0.38 nm thickness ribbon morphology. Interestingly, there were bulges around the edges of HGR. Compared to G and graphene oxide (GO), HGR increased seed germination by 15% root differentiation between 52 and 59% and enhanced resistance to oxidative stress. The metabonomics analysis discovered that HGR upregulated carbohydrate, amino acid, and fatty acids metabolism that determined secondary metabolism, nitrogen sequestration, cell membrane integrity, permeability, and oxidation resistance. Hexadecanoic acid as a biomarker promoted root differentiation and increased the germination rate. Our discovery is a novel HGR that promotes aged seed germination, illustrates metabolic specificity among graphene-based materials, and inspires innovative concepts in the regulation of seed development.

  8. Gianturco-Rösch Z stents in tracheobronchial stenoses.

    Science.gov (United States)

    Petersen, B D; Uchida, B T; Barton, R E; Keller, F S; Rösch, J

    1995-01-01

    To evaluate expandable metallic Gianturco-Rösch Z (GRZ) stents for treatment of benign and malignant tracheobronchial stenoses. Six patients, ages 45-73 years, were treated for severe dyspnea with placement of GRZ stents. Three patients had benign tracheal lesions (one tracheomalacia, two postoperative) and received uncovered GRZ stents. Three patients had malignant stenoses at the level of the carina; one received an uncovered stent and the other two received silicone-covered GRZ stents. Two patients with benign lesions responded well to stent placement. One was asymptomatic for a year and then was lost to follow-up; the other improved substantially but died of end-stage lung disease 5 months after stent placement. A third patient with a benign high tracheal lesion did poorly; symptoms recurred secondary to inferior migration of a stent, which was removed surgically at 4 months. All patients with malignant lesions improved symptomatically after stent placement and remained without significant dyspnea until death (from 1 to 6 months). Expandable GRZ stents are promising devices for treatment of benign lesions and offer effective palliation of malignant tracheobronchial stenoses.

  9. Peripheral surgical wounding and age-dependent neuroinflammation in mice.

    Directory of Open Access Journals (Sweden)

    Zhipeng Xu

    Full Text Available Post-operative cognitive dysfunction is associated with morbidity and mortality. However, its neuropathogenesis remains largely to be determined. Neuroinflammation and accumulation of β-amyloid (Aβ have been reported to contribute to cognitive dysfunction in humans and cognitive impairment in animals. Our recent studies have established a pre-clinical model in mice, and have found that the peripheral surgical wounding without the influence of general anesthesia induces an age-dependent Aβ accumulation and cognitive impairment in mice. We therefore set out to assess the effects of peripheral surgical wounding, in the absence of general anesthesia, on neuroinflammation in mice with different ages. Abdominal surgery under local anesthesia was established in 9 and 18 month-old mice. The levels of tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, Iba1 positive cells (the marker of microglia activation, CD33, and cognitive function in mice were determined. The peripheral surgical wounding increased the levels of TNF-α, IL-6, and Iba1 positive cells in the hippocampus of both 9 and 18 month-old mice, and age potentiated these effects. The peripheral surgical wounding increased the levels of CD33 in the hippocampus of 18, but not 9, month-old mice. Finally, anti-inflammatory drug ibuprofen ameliorated the peripheral surgical wounding-induced cognitive impairment in 18 month-old mice. These data suggested that the peripheral surgical wounding could induce an age-dependent neuroinflammation and elevation of CD33 levels in the hippocampus of mice, which could lead to cognitive impairment in aged mice. Pending further studies, anti-inflammatory therapies may reduce the risk of postoperative cognitive dysfunction in elderly patients.

  10. The impact of the distance-dependent promotional effect on the promotion cost sharing decision

    Science.gov (United States)

    Sheen, Gwo-Ji; Wang, Shih-Yen; Yeh, Yingchieh

    2016-02-01

    This paper considers the promotion cost sharing decision between a supplier and a retailer. The customer demand is affected by both national and local promotional effects while the local promotional effect on a customer is dependent on the distance between the retailer and this customer. We propose a continuous approximation approach to modelling the sum of the customer demand in the whole market area served by the retailer. A model is provided to help managers decide on the retail price, the local advertising expenditure, the national advertising expenditure, and the supplier participation rate, with consideration of the influence of distance on the promotional effect. We also find that the supplier's promotion cost sharing rate increases as the market size increases or the influence of distance on the promotional effect decreases. A numerical example is given to show that the nature of distance-dependent promotional effect has a significant impact on the decisions and profits.

  11. Milk—A Nutrient System of Mammalian Evolution Promoting mTORC1-Dependent Translation

    Science.gov (United States)

    Melnik, Bodo C.

    2015-01-01

    Based on own translational research of the biochemical and hormonal effects of cow’s milk consumption in humans, this review presents milk as a signaling system of mammalian evolution that activates the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1), the pivotal regulator of translation. Milk, a mammary gland-derived secretory product, is required for species-specific gene-nutrient interactions that promote appropriate growth and development of the newborn mammal. This signaling system is highly conserved and tightly controlled by the lactation genome. Milk is sufficient to activate mTORC1, the crucial regulator of protein, lipid, and nucleotide synthesis orchestrating anabolism, cell growth and proliferation. To fulfill its mTORC1-activating function, milk delivers four key metabolic messengers: (1) essential branched-chain amino acids (BCAAs); (2) glutamine; (3) palmitic acid; and (4) bioactive exosomal microRNAs, which in a synergistical fashion promote mTORC1-dependent translation. In all mammals except Neolithic humans, postnatal activation of mTORC1 by milk intake is restricted to the postnatal lactation period. It is of critical concern that persistent hyperactivation of mTORC1 is associated with aging and the development of age-related disorders such as obesity, type 2 diabetes mellitus, cancer, and neurodegenerative diseases. Persistent mTORC1 activation promotes endoplasmic reticulum (ER) stress and drives an aimless quasi-program, which promotes aging and age-related diseases. PMID:26225961

  12. Milk—A Nutrient System of Mammalian Evolution Promoting mTORC1-Dependent Translation

    Directory of Open Access Journals (Sweden)

    Bodo C. Melnik

    2015-07-01

    Full Text Available Based on own translational research of the biochemical and hormonal effects of cow’s milk consumption in humans, this review presents milk as a signaling system of mammalian evolution that activates the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1, the pivotal regulator of translation. Milk, a mammary gland-derived secretory product, is required for species-specific gene-nutrient interactions that promote appropriate growth and development of the newborn mammal. This signaling system is highly conserved and tightly controlled by the lactation genome. Milk is sufficient to activate mTORC1, the crucial regulator of protein, lipid, and nucleotide synthesis orchestrating anabolism, cell growth and proliferation. To fulfill its mTORC1-activating function, milk delivers four key metabolic messengers: (1 essential branched-chain amino acids (BCAAs; (2 glutamine; (3 palmitic acid; and (4 bioactive exosomal microRNAs, which in a synergistical fashion promote mTORC1-dependent translation. In all mammals except Neolithic humans, postnatal activation of mTORC1 by milk intake is restricted to the postnatal lactation period. It is of critical concern that persistent hyperactivation of mTORC1 is associated with aging and the development of age-related disorders such as obesity, type 2 diabetes mellitus, cancer, and neurodegenerative diseases. Persistent mTORC1 activation promotes endoplasmic reticulum (ER stress and drives an aimless quasi-program, which promotes aging and age-related diseases.

  13. Effect of Thyroxin Treatment on Carotid Intima-Media Thickness (CIMT) Reduction in Patients with Subclinical Hypothyroidism (SCH): a Meta-Analysis of Clinical Trials.

    Science.gov (United States)

    Aziz, Muhammad; Kandimalla, Yugandhar; Machavarapu, Archana; Saxena, Anshul; Das, Sankalp; Younus, Adnan; Nguyen, Michelle; Malik, Rehan; Anugula, Dixitha; Latif, Muhammad A; Humayun, Choudhry; Khan, Idrees M; Adus, Ali; Rasool, Aisha; Veledar, Emir; Nasir, Khurram

    2017-07-01

    Research shows that subclinical hypothyroidism (SCH) is related to an increased carotid intima-media thickness (CIMT), a surrogate marker of subclinical cardiovascular disease (CVD). It is controversial whether or not SCH should be treated to reduce CVD morbidity and mortality. This meta-analysis aimed to determine whether SCH is associated with an increase in CIMT as compared to Euthyroidism (EU) and whether thyroxin (T4) treatment in SCH can reverse the change in CIMT. Two independent reviewers conducted an extensive database research up to December 2016. A total of 12 clinical trials discussed the effect of Thyroxin on CIMT values at pre- and post-treatment in subjects with SCH. CIMT was significantly higher among SCH (n=280) as compared to EU controls (n=263) at baseline; the pooled weighted mean difference (WMD) of CIMT was 0.44 mm [95% confidence interval (CI) 0.14, 0.74], p=0.004; I 2 =65%. After treatment with thyroxin in subjects with SCH (n=314), there was a statistically significant decrease in CIMT from pre- to post-treatment; the pooled WMD of CIMT decrease was [WMD -0.32; 95% CI (-0.47, -0.16), p=<0.0001; I 2 =2%], and it was no longer different from EU controls [WMD 0.13 mm; 95% CI (-0.04, 0.30); p=0.14; I 2 =27%]. The total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL) were higher in SCH as compared to EU controls and decreased significantly after treatment with thyroxin. This meta-analysis shows that thyroxin therapy in subjects with SCH significantly decreases CIMT and improves lipid profile, modifiable CVD risk factors. Thyroid hormone replacement in subjects with SCH may play a role in slowing down or preventing the progression of atherosclerosis.

  14. Promoting Healthy Aging in Adults with Developmental Disabilities

    Science.gov (United States)

    Heller, Tamar; Sorensen, Amy

    2013-01-01

    This article reviews the research on health promotion for adults aging with developmental disabilities. First, it examines barriers to healthy aging, including health behaviors and access to health screenings and services. Second, it reviews the research on health promotion interventions, including physical activity interventions, health education…

  15. Total deposition of inhaled particles related to age: comparison with age-dependent model calculations

    International Nuclear Information System (INIS)

    Becquemin, M.H.; Bouchikhi, A.; Yu, C.P.; Roy, M.

    1991-01-01

    To compare experimental data with age-dependent model calculations, total airway deposition of polystyrene aerosols (1, 2.05 and 2.8 μm aerodynamic diameter) was measured in ten adults, twenty children aged 12 to 15 years, ten children aged 8 to 12, and eleven under 8 years old. Ventilation was controlled, and breathing patterns were appropriate for each age, either at rest or at light exercise. Individually, deposition percentages increased with particle size and also from rest to exercise, except in children under 12 years, in whom they decreased from 20-21.5 to 14-14.5 for 1 μm particles and from 36.8-36.9 to 32.2-33.1 for 2.05 μm particles. Comparisons with the age-dependent model showed that, at rest, the observed data concerning children agreed with those predicted and were close to the adults' values, when the latter were higher than predicted. At exercise, child data were lower than predicted and lower than adult experimental data, when the latter agreed fairly well with the model. (author)

  16. Subclinical hypothyroidism is associated with higher carotid intima-media thickness in cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

    Science.gov (United States)

    Peixoto de Miranda, É J F; Bittencourt, M S; Pereira, A C; Goulart, A C; Santos, I S; Lotufo, P A; Bensenor, I M

    2016-10-01

    Although subclinical hypothyroidism (SCH) is associated with cardiovascular risk, there is scarce data about subclinical atherosclerosis in subjects with SCH. We aimed to analyze the association between SCH and carotid intima-media thickness (IMT) using baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). We included subjects with normal thyroid function (TSH: 0.4-4.0 mIU/l, and normal free thyroxine (FT4): 0.8-1.9 ng/dl) and SCH (TSH ≥ 4.0 mIU/l and normal FT4) evaluated for IMT in a cross-sectional analysis. We excluded individuals using medications that affect thyroid function and those with a history of cardiovascular disease. We performed logistic and linear regression models to evaluate the association with IMT (mean values and categorized at the 75th percentile) as a dependent variable and SCH as an independent variable, adjusted for other cardiovascular risk factors. From 8623 subjects (median age of 50 years; interquartile range: 44-57), 4624 (53.6%) were women, 8095 (93.9%) were euthyroid, and 528 (6.1%) had SCH. Groups varied in age, body mass index, Framingham risk score, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR), C-reactive protein, as well as, IMT, that were all higher in SCH compared to euthyroid participants. SCH is associated with IMT as a continuous variable (β = 0.010, P = 0.036) and IMT >75th percentile: OR = 1.30 (95% CI = 1.06-1.59) in logistic models. Individuals with SCH presented higher IMT compared with euthyroid subjects, even after adjustment for potential confounders. IMT was independently associated with SCH in the baseline of the ELSA-Brasil study. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  17. CCR9-CCL25 interactions promote cisplatin resistance in breast cancer cell through Akt activation in a PI3K-dependent and FAK-independent fashion

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    Lillard James W

    2011-05-01

    Full Text Available Abstract Background Chemotherapy heavily relies on apoptosis to kill breast cancer (BrCa cells. Many breast tumors respond to chemotherapy, but cells that survive this initial response gain resistance to subsequent treatments. This leads to aggressive cell variants with an enhanced ability to migrate, invade and survive at secondary sites. Metastasis and chemoresistance are responsible for most cancer-related deaths; hence, therapies designed to minimize both are greatly needed. We have recently shown that CCR9-CCL25 interactions promote BrCa cell migration and invasion, while others have shown that this axis play important role in T cell survival. In this study we have shown potential role of CCR9-CCL25 axis in breast cancer cell survival and therapeutic efficacy of cisplatin. Methods Bromodeoxyuridine (BrdU incorporation, Vybrant apoptosis and TUNEL assays were performed to ascertain the role of CCR9-CCL25 axis in cisplatin-induced apoptosis of BrCa cells. Fast Activated Cell-based ELISA (FACE assay was used to quantify In situ activation of PI3Kp85, AktSer473, GSK-3βSer9 and FKHRThr24 in breast cancer cells with or without cisplatin treatment in presence or absence of CCL25. Results CCR9-CCL25 axis provides survival advantage to BrCa cells and inhibits cisplatin-induced apoptosis in a PI3K-dependent and focal adhesion kinase (FAK-independent fashion. Furthermore, CCR9-CCL25 axis activates cell-survival signals through Akt and subsequent glycogen synthase kinase-3 beta (GSK-3β and forkhead in human rhabdomyosarcoma (FKHR inactivation. These results show that CCR9-CCL25 axis play important role in BrCa cell survival and low chemotherapeutic efficacy of cisplatin primarily through PI3K/Akt dependent fashion.

  18. Chomsky-Schützenberger parsing for weighted multiple context-free languages

    Directory of Open Access Journals (Sweden)

    Tobias Denkinger

    2017-07-01

    Full Text Available We prove a Chomsky-Schützenberger representation theorem for multiple context-free languages weighted over complete commutative strong bimonoids. Using this representation we devise a parsing algorithm for a restricted form of those devices.

  19. Quantitative Evaluation of MMP-9 and TIMP-1 Promoter Methylation in Chronic Periodontitis.

    Science.gov (United States)

    Li, Xiting; Lu, Jiaxuan; Teng, Wei; Zhao, Chuanjiang; Ye, Xiaolei

    2018-03-01

    In this study, we investigated the promoter DNA methylation (DNAm) status of the MMP-9 and TIMP-1 genes in patients with chronic periodontitis to evaluate disease progression. Using pyrosequencing technology, DNAm levels of MMP-9 and TIMP-1 CpG islands were measured in 88 chronic periodontitis patients and 15 healthy controls. We found a positive correlation between methylation levels of MMP-9 CpG islands and the severity of chronic periodontitis. Methylated CpG islands were also closely associated with the duration of chronic periodontitis. Moreover, female patients exhibited lower methylation levels of MMP-9 but higher methylation levels of TIMP-1 compared with male patients, and the methylation levels of TIMP-1 gradually decreased with age. The findings of gender disparity in the DNAm of MMP-9 and TIMP-1 genes provide novel insights into chronic periodontitis.

  20. Joint Affection in Henoch-Schönlein Purpura

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    O.V. Syniachenko

    2016-10-01

    Full Text Available Background. Hemorrhagic vasculitis, or Henoch-Schönlein purpura (HSP, in children has its onset in the form of the articular syndrome in the vast number of patients, which is a part of the diagnostic criteria of this disease. The nature of the arthritis after the disease transformation from the juvenile HSP remains unexplored. In adulthood, articular patho­logy can manifest as migratory intermittent or chronic arthritis, but this information should be clarified. The objective was to study the clinical, X-ray and sonographic features of arti­cular syndrome course in patients with HSP and to evaluate the features of arthropathy in the presence of the disease that began in childhood and adulthood. Materials and methods. The study included 174 patients with HSP (83 % of men and 47 % of women. Childhood-onset vasculitis (on average in 12 years was diagnosed in 92 patients, and adulthood-onset (on avera­ge in 25 years — in 82; I, II and III degree of activity of the pathological process are established at a ratio of 1 : 2 : 2. Results. The joint affection is observed in every second patient with HPS, which is closely related to the patient’s age at the onset of the disease, duration and degree of the activity of pathological process, seropositivity by the high content of immunoglobulin A and rheumatoid factor. At that, clinical, radiological and sonographic nature of the articular syndrome’s course (involving the wrist, hip and sacroiliac joints, the development of aseptic osteonecrosis, bone erosion, meniscitis and intraarti­cular cartilage flaps depend on extraarticular manifestations of the di­sease (lesion of heart, kidney, pancreas, central nervous system. They are accompanied by an increased concentration in the blood of β2-microglobulin and circulating immune complexes that together with the values of fibrinogenemia have predictive value. Dimorphism of HSP, transformed from a juvenile one, is characterized by the less serum levels

  1. Henoch-Schönlein purpura in an older man presenting as rectal bleeding and IgA mesangioproliferative glomerulonephritis: a case report

    Directory of Open Access Journals (Sweden)

    Howarth Charles B

    2011-08-01

    , extensive skin lesions and renal involvement which responds well to systemic steroid therapy. A history of diverticulosis can mislead physicians to the diagnosis of diverticular bleeding which is more common in this age group. The clinical manifestations of the disease, including characteristic skin rash, abdominal pain, joint inflammation and renal involvement raised the suspicious of Henoch-Schönlein purpura.

  2. N-methylisatin-beta-thiosemicarbazone derivative (SCH 16 is an inhibitor of Japanese encephalitis virus infection in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Sriram D

    2008-05-01

    Full Text Available Abstract Background During the early and mid part of 20th century, several reports described the therapeutic effects of N-methylisatin-β-Thiosemicarbazone (MIBT against pox viruses, Maloney leukemia viruses and recently against HIV. However, their ability to inhibit flavivirus replication has not been investigated. Hence the present study was designed to evaluate the antiviral activity of 14 MIBT derivatives against Flaviviruses that are prevalent in India such as Japanese Encephalitis Virus (JEV, Dengue-2 (Den-2 and West Nile viruses (WNV. Results Amongst the fourteen Mannich bases of MIBT derivatives tested one compound – SCH 16 was able to completely inhibit in vitro Japanese encephalitis virus (JEV and West Nile virus (WNV replication. However no antiviral activity of SCH 16 was noted against Den-2 virus replication. This compound was able to inhibit 50% of the plaques (IC50 produced by JEV and WNV at a concentration of 16 μgm/ml (0.000025 μM and 4 μgm/ml (0.000006 μM respectively. Furthermore, SCH 16 at a concentration of 500 mg/kg body weight administered by oral route twice daily was able to completely (100% prevent mortality in mice challenged with 50LD50 JEV by the peripheral route. Our experiments to understand the mechanism of action suggest that SCH 16 inhibited JEV replication at the level of early protein translation. Conclusion Only one of the 14 isatin derivatives -SCH 16 exhibited antiviral action on JEV and WNV virus infection in vitro. SCH 16 was also found to completely inhibit JEV replication in vivo in a mouse model challenged peripherally with 50LD50 of the virus. These results warrant further research and development on SCH 16 as a possible therapeutic agent.

  3. Federal Act on Protection against Nuisances (BImSchG) and supplementing regulations. 11. ed.

    International Nuclear Information System (INIS)

    Hansmann, K.

    1993-01-01

    This handy booklet contains the BImSchG and related implementing regulations as well as the Technical Codes Clean Air and Noise Abatement. The contribution on the BImSchG explains the origin of the Act, the scope of application, its concept and principles. The contents of the Act is portrayed by emphasizing subject-related connections. Dealt with are also regulations for installations requiring licensing, the measurement of airborne pollution, stipulations concerning the area of installations and transport, as well as the regulation concerning the monitoring of airborne pollution in the Federal Republic of Germany. (orig.) [de

  4. High-dose methylprednisolone pulse therapy for treatment of refractory intestinal involvement caused by Henoch-Schönlein purpura: a case report.

    Science.gov (United States)

    Kang, Hyun Sik; Chung, Hee Sup; Kang, Ki-Soo; Han, Kyoung Hee

    2015-03-24

    Henoch-Schönlein purpura is an immunoglobulin A-mediated, small vascular inflammatory disease that can be associated with palpable purpura, arthralgia, abdominal pain, or nephritis. The presence of purpura facilitates the diagnosis of Henoch-Schönlein purpura at the onset of associated symptoms, whereas the absence of purpura makes the diagnosis challenging. It is important to diagnose Henoch-Schönlein purpura with delayed-onset skin purpura to avoid unnecessary surgery for acute abdomen. Most cases of Henoch-Schönlein purpura with severe abdominal pain are treated with low-dose steroids and intravenous immunoglobulin. A 15-year-old Korean girl complained of severe abdominal pain and delayed-onset purpura on admission. Henoch-Schönlein purpura was diagnosed based on endoscopic findings of hemorrhagic duodenitis and duodenal vasculitis and abdominal computed tomography findings of edematous bowels. Two common initial treatments, a low-dose steroid and intravenous immunoglobulin, were administered, but there was no improvement for 1 month. Subsequently, we used high-dose intravenous methylprednisolone pulse therapy (30 mg/kg/day, with a maximum of 1g/day), which dramatically alleviated her abdominal symptoms. High-dose intravenous methylprednisolone pulse therapy can be used as the ultimate treatment for delayed-onset Henoch-Schönlein purpura with severe abdominal pain when symptoms do not improve after low-dose steroid and intravenous immunoglobulin treatments.

  5. Conhecimento tácito e conhecimento escolar na formação do professor (por que Donald Schön não entendeu Luria Tacit knowledge and school knowledge in teachers' education (why Donald Schön didn't understand Luria

    Directory of Open Access Journals (Sweden)

    Newton Duarte

    2003-08-01

    Full Text Available O objetivo do texto é mostrar que os estudos de Donald Schön no campo da formação profissional em geral e da formação de professores em particular pautam-se numa epistemologia que desvaloriza o conhecimento científico/teórico/acadêmico e numa pedagogia que desvaloriza o saber escolar. Nesta direção é feita uma análise crítica das idéias de Schön acerca do conhecimento tácito e do conhecimento escolar. Essa análise crítica das idéias de Schön é inserida no contexto de uma crítica aos pressupostos epistemológicos hegemônicos atualmente no campo dos estudos sobre formação de professores.This paper defends that Donald Schön's works on professional education in general and more particularly on teachers' education are based both on an epistemology that devalues scientific knowledge and on a pedagogy that devalues school knowledge. A critical analysis of Schön's concepts of tacit knowledge (or reflection-in-action and school knowledge is presented. This critical analysis is inserted in the context of a criticism of the currently hegemonic epistemological ideas in the field of studies on teachers' education.

  6. Age-Dependence and Aging-Dependence: Neuronal Loss and Lifespan in a C. elegans Model of Parkinson's Disease.

    Science.gov (United States)

    Apfeld, Javier; Fontana, Walter

    2017-12-23

    It is often assumed, but not established, that the major neurodegenerative diseases, such as Parkinson's disease, are not just age-dependent (their incidence changes with time) but actually aging-dependent (their incidence is coupled to the process that determines lifespan). To determine a dependence on the aging process requires the joint probability distribution of disease onset and lifespan. For human Parkinson's disease, such a joint distribution is not available, because the disease cuts lifespan short. To acquire a joint distribution, we resorted to an established C. elegans model of Parkinson's disease in which the loss of dopaminergic neurons is not fatal. We find that lifespan is not correlated with the loss of individual neurons. Therefore, neuronal loss is age-dependent and aging-independent. We also find that a lifespan-extending intervention into insulin/IGF1 signaling accelerates the loss of specific dopaminergic neurons, while leaving death and neuronal loss times uncorrelated. This suggests that distinct and compartmentalized instances of the same genetically encoded insulin/IGF1 signaling machinery act independently to control neurodegeneration and lifespan in C. elegans . Although the human context might well be different, our study calls attention to the need to maintain a rigorous distinction between age-dependence and aging-dependence.

  7. Aging promotes todorokite formation from layered manganese oxide at near-surface conditions

    Energy Technology Data Exchange (ETDEWEB)

    Cui, Haojie [Chinese Academy of Sciences, Xiamen (China). Key Lab. of Urban Environment and Health; Huazhong Agricultural Univ., Ministry of Agriculture, Wuhan (China). Key Lab. of Subtropical Agricultural Resources and Environment; Liu, Fan; Feng, Xionghan; Tan, Wenfeng [Huazhong Agricultural Univ., Ministry of Agriculture, Wuhan (China). Key Lab. of Subtropical Agricultural Resources and Environment; Wang, Ming Kuang [National Taiwan Univ., Taipei (China). Dept. of Agricultural Chemistry

    2010-12-15

    Todorokite is one common manganese oxide in soils and sediments and is commonly formed from layered Na-buserite. Aging processes can alter the physicochemical properties of freshly formed Na-buserite in natural environments. However, it is not clear whether and how aging affects the formation of todorokites. In the present paper, Na-buserite with aging treatment was employed to prepare todorokite at atmospheric pressure to investigate the effects of aging treatment of Na-buserite on the formation of todorokite. Four aged Na-buserite samples, which are produced through oxidation of Mn{sup 2+} in concentrated NaOH medium by O{sub 2} with aging for 3, 6, 9, and 12 months, were employed to investigate the effects of aging processes on the transformation from Na-buserite to todorokite by Mg{sup 2+}-templating reaction at atmospheric pressure. The manganese oxides were examined using X-ray diffraction (XRD), elemental analysis, determinations of the average manganese oxidation number, infrared spectroscopy (IR), and transmission electron microscopy (TEM). The XRD, IR, and elemental analyses indicate that aging treatment can alter the substructure of the freshly synthesized Na-buserite. During the aging process, some of the Mn(III) may migrate into the interlayer region or disproportionate to form Mn{sup 2+} and Mn{sup 4+} from the layer of Na-buserite and the concomitant formation of layer vacancies. The interlayer Mn{sup 3+} or Mn{sup 2+} occupied above or below the layer vacancy sites and become corner-sharing octahedral. XRD analyses and TEM clearly show that the transformation from Na-buserite to todorokite was promoted by aging treatments. The alterations of substructure of aged Na-buserites can promote the rearrangement of manganese to construct a tunnel structure during the transformation from layered manganese oxides to tunnel-structure todorokite at atmospheric pressure. The transformation from Na-buserite to todorokite was promoted by aging treatments at

  8. Soil and phytosociological characterization of an area with predominance of arnica (Lychnophora pohlii sch. bip.

    Directory of Open Access Journals (Sweden)

    André Rodrigues da Cunha Gianotti

    2013-06-01

    Full Text Available Lychnophora pohlii Sch. Bip. (Asteraceae, known as "Arnica mineira", is widely used in folk medicine and very abundant in the altitude vegetation of rocky grassland. The aim of this work was to study the density of this species and its relationship with soil parameters in rocky grassland in Diamantina, in the Upper Jequitinhonha region, Minas Gerais. Ten contiguous 20 x 50 m plots were marked (total sampled area 10,000 m² on the campus Juscelino Kubitschek of the Federal University of Jequitinhonha and Mucuri Valleys (UFVJM. The plants in these plots were evaluated for frequency, dominance and density. The relationship between the density of this species with nine soil physical and chemical properties was analyzed by means of canonical correspondence analysis (CCA. The highest plant abundance (I of the species Lychnophora pohlii Sch. Bip. was found in the vegetation sampling areas: plot 6 with 255 plants, plot 7 with 173, plot 8 with 189, plot 9 with 159, and plot 1 with 151 plants. In these areas, the floristic soil characteristics were similar, resulting in spatial proximity in the ACC diagrams. The density of Lychnophora pohlii was higher in plots with higher pH, P-rem and base saturation, the variables most strongly correlated with the first axis of canonical correspondence analysis.

  9. Measles virus antibody responses in children randomly assigned to receive standard-titer edmonston-zagreb measles vaccine at 4.5 and 9 months of age, 9 months of age, or 9 and 18 months of age.

    Science.gov (United States)

    Martins, Cesario; Garly, May-Lill; Bale, Carlitos; Rodrigues, Amabelia; Njie-Jobe, Jainaba; Benn, Christine S; Whittle, Hilton; Aaby, Peter

    2014-09-01

    The World Health Organization recommends administration of measles vaccine (MV) at age 9 months in low-income countries. We tested the measles virus antibody response at 4.5, 9, 18, and 24 months of age for children randomly assigned to receive standard-titer Edmonston-Zagreb MV at 4.5 and 9 months, at 9 months, or at 9 and 18 months of age. At 4.5 months of age, 75% had nonprotective measles virus antibody levels. Following receipt of MV at 4.5 months of age, 77% (316/408) had protective antibody levels at 9 months of age; after a second dose at 9 months of age, 97% (326/337) had protective levels at 24 months of age. In addition, the response at both 9 and 24 months of age was inversely correlated with the antibody level at receipt of the first dose of MV, and the second dose of MV, received at 9 months of age, provided a significant boost in antibody level to children who had low antibody levels. In the group of 318 children who received MV at 9 months of age, with or without a second dose at 18 months of age, 99% (314) had protective levels at 24 months of age. The geometric mean titer at 24 months of age was significantly lower in the group that received MV at 4.5 and 9 months of age than in the group that received MV at 9 months of age (P = .0001). In conclusion, an early 2-dose MV schedule was associated with protective measles virus antibody levels at 24 months of age in nearly all children. Clinical Trials Registration. NCT00168558. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Henoch-Schönlein purpura: a long-term prospective study in Greek children.

    Science.gov (United States)

    Fretzayas, Andrew; Sionti, Irini; Moustaki, Maria; Papadimitriou, Anastasios; Nicolaidou, Polyxeni

    2008-12-01

    Henoch-Schönlein purpura is a common vasculitis of childhood. The present study, comprising 74 children enrolled during a 9-year period, aimed to delineate the clinical spectrum and the long term follow-up of the disease. Patients were diagnosed strictly on the criteria established by the American College of Rheumatology. The diagnosis was further strengthened by a skin biopsy performed in more than half of cases (42/74), which revealed leukocytoclastic vasculitis in all patients, whereas IgA deposits were found in 37/42 children. There was a predominance of boys (41 males), and the mean age of study population was 5.2 +/- 2.54 years. Palpable purpura was identified in 73/74 children, whereas transient arthritis manifested in 68/74 children. Gastrointestinal blood loss was elicited in 30 children, 11 of whom had also renal involvement. The latter was seen in 19/74 (25.7%) children, and in the long term follow-up (extended to 2004, from 4-12 years, mean duration 7.3 years), 2 children remained with persistent occult hematuria. Relapses occurred in 49 children (66%), and half of them experienced more than 1 recurrence. Arthritis was less common in the relapsed episodes, and this difference was statistically significant (P period. Recurrences often differ to some extent from the initial episode with arthritis being less common with relapses.

  11. [Clinical characteristics of Henoch-Schönlein purpura in children].

    Science.gov (United States)

    Liu, Li-Jun; Yu, Jing; Li, Yu-Ning

    2015-10-01

    To explore the clinical characteristics of Henoch-Schönlein purpura (HSP) in children. The clinical data of 325 hospitalized children who were diagnosed with HSP between June 2012 and June 2014 were analyzed retrospectively. In the 325 children with HSP, the incidence of HSP was higher in winter and spring, with 33.9% and 27.4%, respectively. Infection was the major factor to induce HSP (57.2%). The incidence of renal damage in children with purpura accompanied by abdominal symptoms and children with purpura accompanied by abdominal and joint symptoms was 60.3% and 48.9%, respectively, with statistically significant differences compared with children with purpura alone (Ppurpura nephritis, the pathological grades of IIIa and IIIb were more common, accounting for 28% and 31%, respectively. In 325 children, an increased serum D-dimer level was observed in 260 children (80.0%), an increased peripheral IgA content in 101 children (46.3%), and a decreased CD4+ cell percentage in 62 children (56.4%). A high incidence of HSP is often seen in spring and winter. HSP is often induced by upper respiratory tract infection. Renal damage is more likely to occur in children with digestive tract symptoms, with IIIa and IIIb as the common pathological grades of renal damage.

  12. Structural developmental psychology and health promotion in the third age.

    Science.gov (United States)

    Bauger, Lars; Bongaardt, Rob

    2017-01-12

    In response to the ever-increasing longevity in Western societies, old age has been divided into two different periods, labelled the third and fourth age. Where the third age, with its onset at retirement, mostly involves positive aspects of growing old, the fourth age involves functional decline and increased morbidity. This article focuses on the entry to the third age and its potential for health promotion initiatives. Well-being is an important factor to emphasize in such health promotion, and this article views the lifestyle of third agers as essential for their well-being. The structural developmental theory of Robert Kegan delineates how a person's way of knowing develops throughout the life course. This theory is an untapped and salient perspective for health promotion initiatives in the third age. This article outlines Kegan's approach as a tool for developing psychologically spacious health promotion, and suggests future directions for research on the topic. © The Author 2017. Published by Oxford University Press.

  13. Intuition in medical practice: A reflection on Donald Schön's reflective practitioner.

    Science.gov (United States)

    Mickleborough, Tim

    2015-01-01

    In a recent commentary, Dr. Abhishek Biswas asks the question whether physicians should rely on their "gut feeling" when making clinical decisions. Biswas describes a situation where his intuition resulted in an immediate course of action that prompted urgent medical attention for a patient who had "routine" pain. Inspired by the author's account, I would like to further Biswas' discussion and examine its importance using the educational theories of Donald Schön and his concept of the reflective practitioner. Schön argues that technical knowledge alone is not sufficient to solve the complex problems that professionals face on a daily basis and intuition, developed through a reflective practice, is crucial for any professional's practice, especially in a time of greater uncertainty in the workplace.

  14. Exercise Promotes Healthy Aging of Skeletal Muscle

    DEFF Research Database (Denmark)

    Cartee, Gregory D; Hepple, Russell T; Bamman, Marcas M

    2016-01-01

    caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial...... respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes "healthy aging" by inducing modifications in skeletal muscle....

  15. Non-thrombocytopenic purpura in familial Mediterranean fever-comorbidity with Henoch-Schönlein purpura or an additional rare manifestation of familial Mediterranean fever?

    Science.gov (United States)

    Ben-Chetrit, Eldad; Yazici, Hasan

    2016-07-01

    Henoch-Schönlein purpura is a relatively common vasculitis mainly affecting children. It is characterized by purpuric skin rash, abdominal cramping, and haematuria. Skin biopsies taken from Henoch-Schönlein purpura lesions disclose perivascular IgA deposits. FMF is an autoinflammatory disease characterized by recurrent attacks of fever lasting 2-3 days which resolve spontaneously. Typical manifestations of the disease are peritonitis, pleuritis, pericarditis, arthritis and erysipelas-like erythema usually affecting the lower limbs. Over the years many reviews emphasized the clinical impression that Henoch-Schönlein purpura is more common among FMF patients than in healthy control population. In this review we summarize these reports and show that sometimes Henoch-Schönlein purpura associated with FMF differs from typical isolated Henoch-Schönlein purpura, and this is also the case with polyarteritis nodosa and SpA associated with FMF. It is suggested that these clinical manifestations (polyarteritis nodosa, Henoch-Schönlein purpura and SpA) should be considered to be associated with FMF as part of what we call FMF rather than as co-existing additional separate clinical entities. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Association of endothelial nitric oxide synthase gene polymorphism with the risk of Henoch-Schönlein purpura/Henoch-Schönlein purpura nephritis.

    Science.gov (United States)

    Zhong, Weiqiang; Zhou, Tian-Biao; Jiang, Zongpei

    2015-04-01

    Association between endothelial nitric oxide synthase (eNOS) gene polymorphism and Henoch-Schönlein purpura (HSP)/Henoch-Schönlein purpura nephritis (HSPN) risk is still controversial. A meta-analysis was performed to evaluate the association between eNOS gene polymorphism and HSP/HSPN susceptibility. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic database. Three articles were identified for the analysis of association between eNOS gene polymorphism and HSPN/HSP risk. eNOS G894T gene polymorphism was not associated with HSPN susceptibility and the risk of patients with HSP developing into HSPN. Interestingly, eNOS G894T T allele and GG genotype were associated with HSP susceptibility, but not the TT genotype. eNOS T786C TT genotype was associated with HSPN susceptibility, but not C allele and CC genotype. Furthermore, eNOS T786C gene polymorphism was not associated with HSP risk and the risk of patients with HSP developing into HSPN. In conclusion, eNOS T786C TT genotype was associated with and eNOS G894T T allele and GG genotype were associated with HSP susceptibility. However, more studies should be performed in the future.

  17. Mädchenschule und Geschlecht: Eine fallrekonstruktive Untersuchung der kollektiven Orientierungen und Weiblichkeitskonstruktionen von Schülerinnen monoedukativer Schulen

    OpenAIRE

    Waburg, Wiebke

    2010-01-01

    Die Dissertation ist im Rahmen des Projektes "Schulkultur, Geschlechtersegregation und Mädchensozialisation – DIAM" (Projektleitung L. Herwartz-Emden; gefördert von der DFG) entstandenen. In der Arbeit erfolgt die Rekonstruktion der Geschlechtskonstruktionen von Schülerinnen aus Mädchenschulen. Untersucht werden die kollektiven (geschlechtsbezogenen) Orientierungen von Mädchen und jungen Frauen im Alter von 13-19 Jahren. Die Schülerinnen befinden sich in der kulturell definierten Altersphase ...

  18. Lasing characteristics of 1.5 μm GaInAsP-InP SCH-BIG-DR lasers

    International Nuclear Information System (INIS)

    Shim, J.I.; Komori, K.; Arai, S.; Arima, I.; Suematsu, Y.; Somchai, R.

    1991-01-01

    This paper reports that higher differential quantum efficiency η df , smaller chirp Δλ, narrower linewidth Δν, and high coupling efficiency C out between active and passive regions of 1.5 μm GaInAsP/In PSCH-BIG-Dr lasers with a thin active layer and asymmetric gratings are experimentally demonstrated by a comparison of those properties of DFB lasers from the same wafer. A submode suppression ratio (SMSR) of more than 39 dB at 1.7 times the threshold current and a C out of almost 100% in the SCH-BIG-DR lasers indicated that a separate-confinement-heterostructure (SCH) with a thin active layer and a bundle-integrated-guide (BIG) structure are quite adequate to realize high-performance distributed reflector (DR-type lasers) a two times larger η df and 16 times larger front-to-rear output ratio (FROR) of SCH-BIG-DR lasers that those of DFB lasers showed the superiority of DR lasers for high-efficiency operation. Furthermore, superior spectral characteristics of the SCH-BIG-DR laser in comparison to those of conventional DFB lasers, i.e., only about a half of chirping under a rapid direction modulation, as well as 1/5 of the linewidth-power product, were also obtained, which originated from the smaller effective linewidth enhancement factor α eff of the DR laser

  19. An adult patient with Henoch-Schönlein purpura and non-occlusive mesenteric ischemia

    Science.gov (United States)

    2013-01-01

    Background Onset of Henoch-Schönlein purpura (HSP) in middle age is uncommon, and adults with renal or gastrointestinal involvement present with more severe disease than do similar pediatric patients. Case presentation We present the case of a 69-year-old male with HSP who, after treatment with steroids, cyclophosphamide, and continuous intravenous prostaglandin E1 (PGE1), died as a result of severe gastrointestinal involvement with non-occlusive mesenteric ischemia (NOMI). Vascular narrowing associated with the NOMI improved after catheter injection of PGE1 and prednisolone, but the patient died of bleeding from an exposed small vessel. At autopsy there was no active vasculitis in the jejunal submucosa. Conclusion Treatment with PGE1 and prednisolone might improve small-vessel vasculitis associated with NOMI. PMID:23343144

  20. Clinical outcomes in children with Henoch-Schönlein purpura nephritis without crescents.

    Science.gov (United States)

    Delbet, Jean Daniel; Hogan, Julien; Aoun, Bilal; Stoica, Iulia; Salomon, Rémi; Decramer, Stéphane; Brocheriou, Isabelle; Deschênes, Georges; Ulinski, Tim

    2017-07-01

    Henoch-Schönlein purpura is the most common vasculitis in children. Its long-term prognosis depends on renal involvement. The management of Henoch-Schönlein purpura nephritis (HSPN) remains controversial. This study reports the prognosis of children with HSPN presenting with class 2 International Study of Kidney Disease in Children (ISKDC) nephritis. All children with HSPN class 2 diagnosed between 1995 and 2015 in four pediatric nephrology centers were included, and clinical and biological data were collected from the medical files. The primary endpoint was proteinuria remission defined as a proteinuria 3 g/L, 52% proteinuria between 1 and 3 g/L, and 18% proteinuria <1 g/L. Forty-seven percent of patients received orally treatment with steroids alone, 37% received methylprednisolone pulses followed by steroids orally, 18% received no steroids. Although 85% reached remission during follow-up, 12% did not maintain complete remission over time so that only 75% remained in complete remission by the end of the follow-up. Univariate analysis found a higher likelihood of remission in patients with higher proteinuria at disease onset (p = 0.009). This trend was not found in the multivariate analysis after adjusting for treatments, as patients with higher proteinuria were most often treated with steroids. Our study shows that one fourth of patients with HSPN class 2 remain proteinuric and thus carry the risk of developing chronic kidney disease over the long term. This finding, together with the better outcome of patients treated with steroids, is in favor of using high-dose steroids orally or IV in these patients.

  1. Synthesis of 11C-SCH 23390, a dopamine D-1 receptor antagonist, for use in in vivo receptor binding studies with PET

    International Nuclear Information System (INIS)

    Halldin, Christer; Stone-Elander, Sharon; Farde, Lars; Ehrin, Erling; Fasth, Karl-Johan; Langstroem, Bengt; Sedvall, Goeran; Karolinska Hospital, Stockholm; Uppsala Univ.

    1986-01-01

    Central dopamine receptors are generally accepted to exist in at least two distinct subtypes: D-1 and D-2. Recently a benzazepine, SCH 23390, was reported to be a selective D-1 dopaminergic antagonist. PET studies of the radio-brominated 76 Br-SCH 23390 reported by Friedman, et al. indicated that the analog exhibits specific binding in the striatum of the monkey brain. Here we report the synthesis of 11 C-SCH 23390 suitable for the in vivo study of dopamine D-1 receptors in the human brain. (author)

  2. 32 CFR 48.302 - Substantiating evidence regarding dependency and age of dependents.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Substantiating evidence regarding dependency and age of dependents. 48.302 Section 48.302 National Defense Department of Defense OFFICE OF THE... Designation of Beneficiaries § 48.302 Substantiating evidence regarding dependency and age of dependents. At...

  3. Radiological analysis of peptic ulcer in pediatric age group

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Pyo Nyun; Han, Soon Im; Chung, Moo Chan; Kwon, Kui Hyang; Suh, Won Hyuck [Soon Chun Hyang University College of Medicine, Seoul (Korea, Republic of)

    1984-03-15

    The UGI studies had been performed to 238 patients below the age of 15 years during the period from Jan. 1979 to Jul. 1983 in SCH hospital. The results are as follows: 1. Among 238 cases, 48 cases revealed peptic ulcers of stomach or duodenum (20.2%). The ulcer was in 31/37 cases of male patients (22.6%), and in 17/101 cases of female (16.8). Below the age of 5 years, ulcer was noted in 9 cases among 61 cases (14.8%), whereas above 5 years, in 39 cases among 177 patients (22.0%). 2. In the age group below 5 years, mostly the objective symptoms were discovered (8/9), but above 5 years, complained of subjective symptoms (30/39). 3. The predominant site of peptic ulcer was gastric antrum in the age group below 5 years (7/9), whereas duodenal bulb above 5 years (33/43). 4. Gastric antrum or duodenal bulb deformity was revealed in 13 cases and most of them were in the age group above 5 years. 5. All lesions of peptic ulcers in this study were benign in nature. 6. In follow up study after 1 or 2 months, ulcer was decreased in size strikingly (9/11)

  4. Radiological analysis of peptic ulcer in pediatric age group

    International Nuclear Information System (INIS)

    Kim, Pyo Nyun; Han, Soon Im; Chung, Moo Chan; Kwon, Kui Hyang; Suh, Won Hyuck

    1984-01-01

    The UGI studies had been performed to 238 patients below the age of 15 years during the period from Jan. 1979 to Jul. 1983 in SCH hospital. The results are as follows: 1. Among 238 cases, 48 cases revealed peptic ulcers of stomach or duodenum (20.2%). The ulcer was in 31/37 cases of male patients (22.6%), and in 17/101 cases of female (16.8). Below the age of 5 years, ulcer was noted in 9 cases among 61 cases (14.8%), whereas above 5 years, in 39 cases among 177 patients (22.0%). 2. In the age group below 5 years, mostly the objective symptoms were discovered (8/9), but above 5 years, complained of subjective symptoms (30/39). 3. The predominant site of peptic ulcer was gastric antrum in the age group below 5 years (7/9), whereas duodenal bulb above 5 years (33/43). 4. Gastric antrum or duodenal bulb deformity was revealed in 13 cases and most of them were in the age group above 5 years. 5. All lesions of peptic ulcers in this study were benign in nature. 6. In follow up study after 1 or 2 months, ulcer was decreased in size strikingly (9/11)

  5. Bundes-Immissionsschutzgesetz (Federal Nuisance Protection Act). BImSchG, BImSch-Verordnungen, EMASPrivilegV, Biokraft-NachV, TA Luft, TA Laerm, USchadG, TEHG, ZuG 2012, ZuV 2012, EHVV 2012, FlugISchG, 2. FlugLSV. 29. ed.; Bundes-Immissionsschutzgesetz. BImSchG, BImSch-Verordnungen, EMASPrivilegV, Biokraft-NachV, TA Luft, TA Laerm, USchadG, TEHG, ZuG 2012, ZuV 2012, EHVV 2012, FlugISchG, 2. FlugLSV

    Energy Technology Data Exchange (ETDEWEB)

    Hansmann, Klaus (ed.)

    2011-07-01

    After a detailed introduction, the book goes into detail about the specifications of the Federal Immission Control Act (BImSchG). Also discussed are all regulations for the implementation of the BImSchG, the EMAS-Privilegierungsverordnung (privileges ordinance), the biofuels sustainibility ordinance (Biokraft-NachV), the Technical Instructions on Air Quality Control (TA Luft) and the Technical Instructions on Noise Control (TA Laerm), the Environmental Damage Act (Umweltschadensgesetz), the Greenhouse Gas Emissions Act (Treibhausgas-Emissionshandelsgesetz), the Allocation Act (Zuteilungsgesetz 2012), the Allocation Ordinance (Zuteilungsverordnung 2012), the Auctioning Ordinance (Emissionshandels-Versteigerungsverordnung 2012), and the Aircraft Noise Act (Gesetz zum Schutz gegen Fluglaerm) and the Ordinance on Noise Protection in Airports (Flugplatz-Schallschutzmassnahmenverordnung).

  6. Cultural aspects of ageing and health promotion.

    Science.gov (United States)

    Mariño, R J

    2015-03-01

    The emphasis of Australian Government policy is on the promotion of good health in later life and positive experiences with ageing. Conceptually, a new gerontology framework has replaced the study of disease, decline, loss and disability. Within this framework, health promotion offers a mechanism by which individuals can be assisted to create environments that offer better opportunities for continued participation in society and improved quality of health and self-care. Oral health is instrumental to older people's health, life satisfaction, quality of life and perception of self. Australia is culturally diverse, composed of numerous ethno-cultural groups coexisting within a larger, predominant culture, creating a multicultural and multiracial society. However, despite this cultural diversity, the well documented ageing profile of the Australian population and repeated calls for comprehensive geriatric assessment, the oral health of older adults remains a challenge for oral health providers and for society. A major challenge will be to translate existing knowledge and experience of disease prevention and health promotion into appropriate programmes for older adults. Health promotion is the key to improving oral health in later life as it encourages older adults to be proactive in regard to their health. Therefore, increased efforts should be directed towards identifying opportunities for health promotion activities and the development of community based models that encourage older people to improve and maintain their oral health. Ignoring opportunities for health promotion may increase inequalities in oral health and may lead to even greater demands for curative and oral rehabilitative services from these groups This article firstly provides a brief rationale for oral health promotion. Its second part explores the influence of culture on health beliefs, behaviours and outcomes in older adults and how oral health can relate to cultural background. The last section

  7. Cuidar em oncologia na perspectiva de Alfred Schütz Cuidado en oncología segundo Alfred Schütz Oncological care according Alfred Schütz

    Directory of Open Access Journals (Sweden)

    Regina Célia Popim

    2005-10-01

    Full Text Available O estudo foi realizado com enfermeiros oncológicos em seu cotidiano de trabalho. O objetivo foi compreender a ação subjetiva desses profissionais a partir de sua relação enfermeiro-doente. O referencial fenomenológico, fundamentado nas idéias de Alfred Schütz, possibilitou essa compreensão. Diante de uma questão orientadora: o que significa para você cuidar em oncologia? descreva para mim, foram obtidos depoimentos, os quais, depois de analisados, permitiram chegar ao típico da ação do cuidador enfermeiro neste cotidiano. O estudo revelou que cuidar em oncologia implica em lidar com o humano em situação de fragilidade; requer uma relação de afetividade; é um cuidado que traz consigo a gênese do desgaste profissional. O cuidado em oncologia reveste-se de grande complexidade, requerendo do profissional uma competência que vai para além da esfera técnico-científica. Nesse sentido, o enfermeiro necessita buscar por estratégias que lhe possibilitem o enfrentamento do desgaste a que é submetido em seu trabalho.El estudio fue realizado con enfermeros oncológicos en su cotidiano de trabajo. El objetivo fue comprender la acción subjetiva de esos profesionales desde la relación enfermero-enfermo. El referencial fenomenológico, fundamentado en las ideas de Alfred Schütz, posibilitó esa comprensión. Delante de una cuestión orientadora: ¿qué significa para usted el cuidado en oncología? Descríbame, se obtuvo declaraciones que, tras análisis, permitieron llegar a lo que es típico en la acción cotidiana del cuidador enfermero. El estudio reveló que cuidar en oncología implica tratar con el ser humano en situación de fragilidad; requiere una relación de afectividad; es un cuidado que trae consigo la génesis del desgaste profesional. El cuidado en oncología se reviste de gran complejidad y requiere del profesional una competencia que va más allá de la esfera técnico-científica. En ese sentido, el enfermero

  8. Penetration of radionuclides across the skin. Rat age dependent promethium permeation through skin in vitro

    International Nuclear Information System (INIS)

    Kassai, Z.; Kassai, A.; Bauerova, K.; Koprda, V.; Harangozo, M.; Bendova, P.; Bujnova, A.

    2003-01-01

    The composition and the permeation properties of the skin are dependent on age. In the animal models for permation studies, age affects the mechanical as well as the permeation properties significantly. The time dependence of permeation of 147 Pm 3+ from aqueous solution was established by the animal skin model and the age dependence of promethium permeation through the skin was examined. The aim was to find the optimum rat skin age model for radionuclide permeation studies and to assess the relative importance of the main permeation pathways: transepidermal and transfollicular permeation. The skin from 5-day-old rats (5DR) was found to represent the optimum animal model to study transepidermal permeation of ions. The skin from 9-day-old rats (9DR) was selected to study transfollicular permeation of ions. Comparison of the permeated amounts of promethium through the skin without hairs (3 DR to 6 DR) and with hairs (7DR to 12DR) showed that the additional permation mode via follicles significantly contributed to the permeation rate and extent. (author)

  9. Heinrich Schütz as European cultural agent at the Danish courts

    DEFF Research Database (Denmark)

    Moe, Bjarke

    2011-01-01

    that Schütz in his Danish engagement was far more than an esteemed composer. As cultural agent with contacts throughout Europe he played an important role in providing the Danish courts with desirable musicians and music. While staying in the Danish capital he extended his European network in a way so that he......Based on recent studies of sources linked to the musical milieus at the Danish courts, this article argues that Heinrich Schütz acted as European cultural agent in musical affairs while staying in Copenhagen. As Kapelmester at the Danish Court (1633-35 and 1642-44) he built up the chapel...... by engaging musicians from his own circles, e.g. members of the Saxon Hofkapelle as well as members of his own family. Both Danish Courts, the King's and the Prince-elect's, enjoyed his contacts with several European musical centres, from where he among other things purchased new music. The paper shows...

  10. Exercise Promotes Healthy Aging of Skeletal Muscle.

    Science.gov (United States)

    Cartee, Gregory D; Hepple, Russell T; Bamman, Marcas M; Zierath, Juleen R

    2016-06-14

    Primary aging is the progressive and inevitable process of bodily deterioration during adulthood. In skeletal muscle, primary aging causes defective mitochondrial energetics and reduced muscle mass. Secondary aging refers to additional deleterious structural and functional age-related changes caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes "healthy aging" by inducing modifications in skeletal muscle. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. CARD9-Dependent Neutrophil Recruitment Protects against Fungal Invasion of the Central Nervous System.

    Directory of Open Access Journals (Sweden)

    Rebecca A Drummond

    2015-12-01

    Full Text Available Candida is the most common human fungal pathogen and causes systemic infections that require neutrophils for effective host defense. Humans deficient in the C-type lectin pathway adaptor protein CARD9 develop spontaneous fungal disease that targets the central nervous system (CNS. However, how CARD9 promotes protective antifungal immunity in the CNS remains unclear. Here, we show that a patient with CARD9 deficiency had impaired neutrophil accumulation and induction of neutrophil-recruiting CXC chemokines in the cerebrospinal fluid despite uncontrolled CNS Candida infection. We phenocopied the human susceptibility in Card9-/- mice, which develop uncontrolled brain candidiasis with diminished neutrophil accumulation. The induction of neutrophil-recruiting CXC chemokines is significantly impaired in infected Card9-/- brains, from both myeloid and resident glial cellular sources, whereas cell-intrinsic neutrophil chemotaxis is Card9-independent. Taken together, our data highlight the critical role of CARD9-dependent neutrophil trafficking into the CNS and provide novel insight into the CNS fungal susceptibility of CARD9-deficient humans.

  12. Active Aging Promotion: Results from the Vital Aging Program

    Directory of Open Access Journals (Sweden)

    Mariagiovanna Caprara

    2013-01-01

    Full Text Available Active aging is one of the terms in the semantic network of aging well, together with others such as successful, productive, competent aging. All allude to the new paradigm in gerontology, whereby aging is considered from a positive perspective. Most authors in the field agree active aging is a multidimensional concept, embracing health, physical and cognitive fitness, positive affect and control, social relationships and engagement. This paper describes Vital Aging, an individual active aging promotion program implemented through three modalities: Life, Multimedia, and e-Learning. The program was developed on the basis of extensive evidence about individual determinants of active aging. The different versions of Vital Aging are described, and four evaluation studies (both formative and summative are reported. Formative evaluation reflected participants’ satisfaction and expected changes; summative evaluations yielded some quite encouraging results using quasi-experimental designs: those who took part in the programs increased their physical exercise, significantly improved their diet, reported better memory, had better emotional balance, and enjoyed more cultural, intellectual, affective, and social activities than they did before the course, thus increasing their social relationships. These results are discussed in the context of the common literature within the field and, also, taking into account the limitations of the evaluations accomplished.

  13. Active aging promotion: results from the vital aging program.

    Science.gov (United States)

    Caprara, Mariagiovanna; Molina, María Ángeles; Schettini, Rocío; Santacreu, Marta; Orosa, Teresa; Mendoza-Núñez, Víctor Manuel; Rojas, Macarena; Fernández-Ballesteros, Rocío

    2013-01-01

    Active aging is one of the terms in the semantic network of aging well, together with others such as successful, productive, competent aging. All allude to the new paradigm in gerontology, whereby aging is considered from a positive perspective. Most authors in the field agree active aging is a multidimensional concept, embracing health, physical and cognitive fitness, positive affect and control, social relationships and engagement. This paper describes Vital Aging, an individual active aging promotion program implemented through three modalities: Life, Multimedia, and e-Learning. The program was developed on the basis of extensive evidence about individual determinants of active aging. The different versions of Vital Aging are described, and four evaluation studies (both formative and summative) are reported. Formative evaluation reflected participants' satisfaction and expected changes; summative evaluations yielded some quite encouraging results using quasi-experimental designs: those who took part in the programs increased their physical exercise, significantly improved their diet, reported better memory, had better emotional balance, and enjoyed more cultural, intellectual, affective, and social activities than they did before the course, thus increasing their social relationships. These results are discussed in the context of the common literature within the field and, also, taking into account the limitations of the evaluations accomplished.

  14. Age-dependent dosimetry and metabolism

    International Nuclear Information System (INIS)

    Taylor, D.M.

    1992-01-01

    The release of radionuclides into the environment following the Chernobyl disaster in 1986 created an urgent need for internationally acceptable dose coefficients for calculating the doses delivered to all members of the public, from conception to old age. Organ masses and the kinetics of distribution and retention of elements in humans generally vary with age and often not in simple linear relationship to body weight. Unless variations are considered calculated radiation doses to children may be seriously underestimated. The International Commission on Radiological Protection created in 1987 a Task Group on Age-dependent Doses to Members of the Public from Intake of Radionuclides (AGDOS). The work of AGDOS and the general problems encountered in deriving age-dependent dose coefficients will be discussed in this paper. The first two AGDOS reports, ICRP Publication 56 Parts 1 and 2, provide dose coefficients for the ages 3 months, 1, 5, 10, 15 years and for adults for the 21 elements considered to be of most immediate importance for radiation protection. To develop these dose coefficients, the ICRP Publication 30 dosimetric and biokinetic models were reevaluated and extended. The basic dosimetric model is retained but equivalent dose is now integrated from age at intake to 70 years and the new ICRP Publication 60 tissue weighting factors are incorporated. The development of age-dependent biokinetic models is complicated by the lack of age-related human, or even animal data for the majority of the elements. Thus in formulating the models it has been necessary to use all the available information, biokinetic, physiological chemical and biochemical, and to adopt a number of new approaches including the development of generic biokinetic models for chemically related families of elements such as the actinides and the alkaline earth elements. (author)

  15. Bone and heart abnormalities of subclinical hyperthyroidism in women below the age of 65 years.

    Science.gov (United States)

    Rosario, Pedro Weslley

    2008-12-01

    The objective of the present study was to evaluate bone and cardiac abnormalities and symptoms and signs of thyroid hormone excess in women with subclinical hyperthyroidism (SCH) aged symptom rating scale score was significantly higher in patients. Cardiac involvement, both morphological and affecting systolic and diastolic functions, was also observed in patients. Women with SCH showed a significant increase in serum markers of bone formation and resorption. In addition, bone mineral density (BMD) was lower in the femoral neck but not in the lumbar spine in patients before menopause, whereas a lower BMD was observed at both sites in postmenopausal patients. SCH is not completely asymptomatic in women aged < 65 years, and is associated with heart abnormalities and with increased bone turnover and reduced BMD even before menopause.

  16. Unified inelastic constitutive equations incorporating dynamic strain aging for Mod. 9Cr-1Mo steel

    International Nuclear Information System (INIS)

    Yaguchi, Masatsugu; Takahashi, Yukio

    1998-01-01

    A unified constitutive model considering dynamic strain aging effect was developed in order to describe inelastic deformation behavior of the Mod. 9Cr-1Mo steel precisely. The inelastic behavior of the steel was summarized as follows. A rate dependent deformation was observed above 500degC, and there was no rate dependency under 400degC. However, stress relaxation behavior was observed even at rate independent temperature region. Further, a stress after relaxation depended on prior loading strain rate, and it showed a higher value as the strain rate was slow. A feature of the proposed constitutive model was that an applied stress consists of three stress components: a back stress, an overstress and an aging stress which corresponds to dynamics strain aging and shows a negative strain rate dependency. The aging stress was measured by strain rate change tests, and it showed larger values as the strain rates were slow and the temperatures were low. The backstress and the overstress were measured by strain dip tests. The backstress was approximately rate independent under 400degC, however it showed rate dependency above 500degC. The overstress showed larger values as the strain rates were fast and the temperatures were high. The material constants were determined systematically based on the measured values of each internal variable. In order to evaluate the validity of the constitutive model, numerical simulations were done for various inelastic deformation behavior of Mod. 9Cr-1Mo steel. The simulations agreed with experimental results very well in all cases. (author)

  17. Craniota, Wirbel- oder Schädeltiere

    Science.gov (United States)

    Schultze, Hans-Peter

    Zu den Craniota zählen alle Chordatiere, die eine dreiteilige Regionalisierung des Körpers in Kopf, Rumpf und Schwanz aufweisen. Der Kopf umfasst (1) das Neurocranium mit Gehirn und komplexen Sinnesorganen zur Wahrnehmung der Umgebung, (2) das Viscerocranium zur Nahrungsaufnahme und zur Ventilation der Kiemen bei den primär wasserlebenden Craniota und (3) das Dermatocranium (S. 38). Letzteres entsteht durch Verknöcherungen im Bindegewebe des Integuments, es dient dem Schutz des Kopfes und trägt im Mundbreich die Zähne. Zusammen bilden die drei Skelettstrukturen die funktionelle Einheit Schädel (Cranium). Außer der (somatischen) Rumpfmuskulatur und dem Axialskelett liegen im Rumpf Kreislauf-, Atmungs-, Verdauungs-, Exkretions- und Fortpflanzungsorgane. Der Schwanz, der Abschnitt hinter der Afteröffnung, die das Ende der Leibeshöhle markiert, dient mit Muskeln und Schwanzflosse der Fortbewegung.

  18. Age- and Gene-Dosage–Dependent Cre-Induced Abnormalities in the Retinal Pigment Epithelium

    Science.gov (United States)

    He, Lizhi; Marioutina, Mariya; Dunaief, Joshua L.; Marneros, Alexander G.

    2015-01-01

    To conditionally inactivate genes in the retinal pigment epithelium (RPE) transgenic mouse strains have been developed, in which Cre recombinase (Cre) expression is driven by an RPE-specific gene promoter. The RPE is a quiescent epithelium, and continuous expression of Cre could affect its function. Here, we tested the hypothesis that continuous postnatal Cre expression in the RPE may lead to cellular abnormalities, which may depend on both age and Cre gene dosage. We therefore examined the eyes of homozygous and heterozygous VMD2-Cre mice at various ages. In VMD2-Cre heterozygous mice variable progressive age-dependent RPE abnormalities were noticed, including attenuation of phalloidin and cytoplasmic active β-catenin staining, reduced cell size, and loss of the typical honeycomb pattern of RPE morphology in those RPE cells that stained for Cre. These morphological RPE abnormalities were not noticed in Cre-negative RPE cells in VMD2-Cre or age-matched control mice. In addition, an abnormal number and morphology of cell nuclei were noticed in a subset of Cre-expressing RPE cells in aged heterozygous VMD2-Cre mice, whereas more severe nuclear abnormalities were observed already in young homozygous VMD2-Cre mice. Thus, continuous postnatal expression of Cre causes abnormalities in the RPE in an age- and Cre gene dosage-dependent manner, which needs to be considered in the interpretation of gene targeting studies in the RPE. PMID:24854863

  19. The relationship between attitudes toward aging and health-promoting behaviours in older adults.

    Science.gov (United States)

    Korkmaz Aslan, Gülbahar; Kartal, Asiye; Özen Çınar, İlgün; Koştu, Nazan

    2017-12-01

    Identifying the factors that are associated with health-promoting behaviours in older adults is necessary to increase their willingness and motivation to participate in health-promotion activities. Understanding context-specific attitudes in relation to their influence on health-promoting behaviours is crucial in designing efficient interventions that foster health-promoting behaviours among older adults. This study aimed to examine the relationships between attitudes towards aging and health-promoting behaviours in older adults in Turkey. The study used a descriptive-correlational design. A convenience sample of 448 community-dwelling older adults who were 65 years and older and cognitively intact were selected from 6 family health centres in the city of Denizli in Turkey. The data were collected between March and June of 2014 using the Attitudes to Aging Questionnaire and the Health-Promoting Lifestyle Profile II. Multiple linear regression analysis was performed to explore the predictors of health-promoting behaviours. Attitudes toward aging, the psychosocial loss subscale, and education were statistically significant predictors of health-promoting behaviours. Attitudes toward aging were the strongest predictor of health-promoting behaviours in older adults. Attitude towards aging is a factor that affects health-promoting behaviours, and it should be considered during interventions for improving health promoting behaviours. © 2017 John Wiley & Sons Australia, Ltd.

  20. On the evidence for human use and control of fire at Schöningen.

    Science.gov (United States)

    Stahlschmidt, Mareike C; Miller, Christopher E; Ligouis, Bertrand; Hambach, Ulrich; Goldberg, Paul; Berna, Francesco; Richter, Daniel; Urban, Brigitte; Serangeli, Jordi; Conard, Nicholas J

    2015-12-01

    When and how humans began to control fire has been a central debate in Paleolithic archaeology for decades. Fire plays an important role in technology, social organization, subsistence, and manipulation of the environment and is widely seen as a necessary adaptation for the colonization of northern latitudes. Many researchers view purported hearths, burnt wooden implements, and heated flints from Schöningen as providing the best evidence for the control of fire in the Lower Paleolithic of Northern Europe. Here we present results of a multianalytical study of the purported hearths along with a critical examination of other possible evidence of human use or control of fire at Schöningen. We conclude that the analyzed features and artifacts present no convincing evidence for human use or control of fire. Our study also shows that a multianalytical, micro-contextual approach is the best methodology for evaluating claims of early evidence of human-controlled fire. We advise caution with macroscopic, qualitative identification of combustion features, burnt flint, and burnt wood without the application of such techniques as micromorphology, Fourier transform infrared (FTIR) spectroscopy, organic petrology, luminescence, and analysis of mineral magnetic parameters. The lack of evidence for the human control of fire at Schöningen raises the possibility that fire control was not a necessary adaptation for the human settlement of northern latitudes in the Lower Paleolithic. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Direct demonstration of D1 dopamine receptors in the bovine parathyroid gland using the D1 selective antagonist [125I]-SCH 23982

    International Nuclear Information System (INIS)

    Monsma, F.J. Jr.; Sibley, D.R.

    1989-01-01

    The presence of D1 dopamine receptors in the parathyroid gland has been proposed based on the demonstration of dopaminergic regulation of adenylate cyclase activity and parathyroid hormone release in dispersed bovine parathyroid cells. Using a radioiodinated D1 selective antagonist [125I]-SCH 23982, we have now directly labeled and characterized the D1 dopamine receptors in bovine parathyroid gland membranes. [125I]-SCH 23982 binds in a saturable manner with high affinity and low nonspecific binding to membranes prepared from bovine parathyroid glands. D1 dopamine receptors are present in this preparation at a concentration of approximately 130 fMoles/mg protein and [125I]-SCH 23982 binding increases with increasing protein concentration in a linear fashion. Determination of the Kd using the association (k1) and dissociation (k-1) rate constants revealed good agreement with the Kd determined by saturation analysis (390 pM vs. 682 pM, respectively). Inhibition of 0.3 nM [125I]-SCH 23982 binding by a series of dopaminergic antagonists verified the D1 nature of this binding site, exhibiting appropriate affinities and rank order of potency. The competition curves of all antagonists exhibited Hill coefficients that were not significantly different from 1. Inhibition of [125I]-SCH 23982 binding by dopamine and other dopaminergic agonists revealed the presence of high and low affinity agonist binding sites. Addition of 200 microM GppNHp effected a complete conversion of high affinity dopamine binding sites to a homogeneous population of low affinity dopamine sites. The D1 receptors identified in the parathyroid gland with [125I]-SCH 23982 appear to be pharmacologically identical with those previously characterized in the central nervous system

  2. The evolution of age-dependent plasticity

    NARCIS (Netherlands)

    Fischer, Barbara; van Doorn, G. Sander; Dieckmann, Ulf; Taborsky, Barbara

    2014-01-01

    When organisms encounter environments that are heterogeneous in time, phenotypic plasticity is often favored by selection. The degree of such plasticity can vary during an organism''s lifetime, but the factors promoting differential plastic responses at different ages or life stages remain poorly

  3. The Old-Age Healthy Dependency Ratio in Europe.

    Science.gov (United States)

    Muszyńska, Magdalena M; Rau, Roland

    2012-09-01

    The aim of this study is to answer the question of whether improvements in the health of the elderly in European countries could compensate for population ageing on the supply side of the labour market. We propose a state-of-health-specific (additive) decomposition of the old-age dependency ratio into an old-age healthy dependency ratio and an old-age unhealthy dependency ratio in order to participate in a discussion of the significance of changes in population health to compensate for the ageing of the labour force. Applying the proposed indicators to the Eurostat's population projection for the years 2010-2050, and assuming there will be equal improvements in life expectancy and healthy life expectancy at birth, we discuss various scenarios concerning future of the European labour force. While improvements in population health are anticipated during the years 2010-2050, the growth in the number of elderly people in Europe may be expected to lead to a rise in both healthy and unhealthy dependency ratios. The healthy dependency ratio is, however, projected to make up the greater part of the old-age dependency ratio. In the European countries in 2006, the value of the old-age dependency ratio was 25. But in the year 2050, with a positive migration balance over the years 2010-2050, there would be 18 elderly people in poor health plus 34 in good health per 100 people in the current working age range of 15-64. In the scenarios developed in this study, we demonstrate that improvements in health and progress in preventing disability will not, by themselves, compensate for the ageing of the workforce. However, coupled with a positive migration balance, at the level and with the age structure assumed in the Eurostat's population projections, these developments could ease the effect of population ageing on the supply side of the European labour market.

  4. Effectiveness of the Vital Aging program to promote active aging in Mexican older adults.

    Science.gov (United States)

    Mendoza-Ruvalcaba, Neyda Ma; Fernández-Ballesteros, Rocío

    2016-01-01

    Aging is not only a population phenomenon but also an experience and an individual reality. Vital Aging ® is a program that considers active aging as the lifelong adaptation process of maximizing health and independence, physical and cognitive functioning, positive affect regulation and control, and social engagement. Through its different versions and editions, it has demonstrated being an effective program to promote active aging. The aim of this study is to determine the effectiveness of the "face-to-face" and "combined" versions of the program to promote active aging in Mexican older adults trial. Seventy-six older adults aged 60 years and over participated in a quasi-experimental study and were recruited in a senior center to participate in the two experimental conditions: Vital Aging face-to-face (VA-FF) (n=35) and Vital Aging combined (VA-C; multimedia/face-to-face) (n=15), and the remaining 26 adults were assigned to a control group. Pretest and posttest assessments were performed after the theoretical-practical intervention. Mean differences and size effects were calculated for estimating the effect of the program. At the end of the study, participants showed improvements in the active aging outcome measures. Positive effects were observed in the frequency of intellectual, cultural - artistic, and social activities, perceptions of aging, satisfaction with social relationships, and self-efficacy for aging. Additionally, those who participated in VA-FF showed better memory performance, meta-memory, and a trend to report less memory problems, while older persons in VA-C showed a trend to have better life satisfaction. No effects were observed in physical activity, frequency of social relationships, and subjective health. Findings show that the Vital Aging program in face-to-face and combined versions encourages active aging in Mexican older persons. These results are in general similar to those found in editions performed in Spain, revealing its consistency

  5. Effectiveness of the Vital Aging program to promote active aging in Mexican older adults

    Science.gov (United States)

    Mendoza-Ruvalcaba, Neyda Ma; Fernández-Ballesteros, Rocío

    2016-01-01

    Introduction Aging is not only a population phenomenon but also an experience and an individual reality. Vital Aging® is a program that considers active aging as the lifelong adaptation process of maximizing health and independence, physical and cognitive functioning, positive affect regulation and control, and social engagement. Through its different versions and editions, it has demonstrated being an effective program to promote active aging. The aim of this study is to determine the effectiveness of the “face-to-face” and “combined” versions of the program to promote active aging in Mexican older adults trial. Methods Seventy-six older adults aged 60 years and over participated in a quasi-experimental study and were recruited in a senior center to participate in the two experimental conditions: Vital Aging face-to-face (VA-FF) (n=35) and Vital Aging combined (VA-C; multimedia/face-to-face) (n=15), and the remaining 26 adults were assigned to a control group. Pretest and posttest assessments were performed after the theoretical–practical intervention. Mean differences and size effects were calculated for estimating the effect of the program. Results At the end of the study, participants showed improvements in the active aging outcome measures. Positive effects were observed in the frequency of intellectual, cultural – artistic, and social activities, perceptions of aging, satisfaction with social relationships, and self-efficacy for aging. Additionally, those who participated in VA-FF showed better memory performance, meta-memory, and a trend to report less memory problems, while older persons in VA-C showed a trend to have better life satisfaction. No effects were observed in physical activity, frequency of social relationships, and subjective health. Conclusion Findings show that the Vital Aging program in face-to-face and combined versions encourages active aging in Mexican older persons. These results are in general similar to those found in

  6. Combining balneotherapy and health promotion to promote active and healthy ageing: the Balaruc-MACVIA-LR® approach.

    Science.gov (United States)

    Blain, H; Bernard, P L; Canovas, G; Raffort, N; Desfour, H; Soriteau, L; Noguès, M; Camuzat, T; Mercier, J; Dupeyron, A; Quéré, I; Laffont, I; Hérisson, C; Solimene, H; Bousquet, J

    2016-12-01

    Scaling up and replication of successful innovative integrated care models for chronic diseases is one of the targets of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). MACVIA-LR ® (MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon) is a Reference Site of the EIP on AHA. The main objective of MACVIA-LR ® is to develop innovative solutions in order to (1) improve the care of patients affected by chronic diseases, (2) reduce avoidable hospitalization and (3) scale up the innovation to regions of Europe. The MACVIA-LR ® project also aims to assess all possible aspects of medicine-including non-pharmacologic approaches-in order to maintain health and prevent chronic diseases. These approaches include hydrotherapy and balneotherapy which can be of great importance if health promotion strategies are considered. Balneotherapy at Balaruc-les-Bains focusses on musculoskeletal diseases and chronic venous insufficiency of the lower limbs. Each year, over 46,000 people attend an 18-day course related to a new falls prevention initiative combining balneotherapy and education. On arrival, each person receives a flyer providing information on the risk of fall and, depending on this risk, a course is proposed combining education and physical activity. A pilot study assesses the impact of the course 6 and 12 months later. This health promotion strategy for active and healthy ageing follows the FEMTEC (World Federation of Hydrotherapy and Climatotherapy) concept.

  7. Age dependence of tritium metabolism

    International Nuclear Information System (INIS)

    Inaba, Jiro

    1983-01-01

    3 H metabolism in vivo was studied by HTO administration to rats of varying ages for examination of the age dependence of 3 H metabolism in humans. When 1 μCi/g body weight of HTO was administered, the time-course changes of urine 3 H showed definite age dependence; the younger the rat, more rapidly did the 3 H concentration decrease. The biological half-life of whole body residues was about 2 days in nursing offsprings and about 4 days in mature rats. Tissue-bound 3 H showed high and rapid distribution to the liver, whereas it was slow in the brain and muscle, and this tendency was more prominent in younger rats. Compared with 3 H in tissue water, the concentration of bound 3 H was relatively high, being prominent in younger rats. The time-course changes of 3 H concentration from both origins also showed age dependence. The in vivo exposure dose after administration of 1 μCi/g body weight of HTO- 3 H was generally smaller in younger rats, the exposure at ages 10 and 25 days being about a half of that of mature rats. Supposing that human metabolism is similar, the estimated dose in one-year-olds after ingestion of 1 μCi/kg body weight of 3 H in the form of HTO is about 3 times that in adults, and that after 1 μCi/kg body weight of 3 H in infants, about a half of that in adults. (Chiba, N.)

  8. AGE-modified basement membrane cooperates with Endo180 to promote epithelial cell invasiveness and decrease prostate cancer survival

    DEFF Research Database (Denmark)

    Rodriguez-Teja, Mercedes; Gronau, Julian H; Breit, Claudia

    2015-01-01

    Biomechanical strain imposed by age-related thickening of the basal lamina and augmented tissue stiffness in the prostate gland coincides with increased cancer risk. Here we hypothesized that the structural alterations in the basal lamina associated with age can induce mechanotransduction pathways...... in prostate epithelial cells (PECs) to promote invasiveness and cancer progression. To demonstrate this, we developed a 3D model of PEC acini in which thickening and stiffening of basal lamina matrix was induced by advanced glycation end-product (AGE)-dependent non-enzymatic crosslinking of its major......(Δ) (Ex2-6/) (Δ) (Ex2-6) mice, with constitutively exposed CTLD2 and decreased survival of men with early (non-invasive) prostate cancer with high epithelial Endo180 expression and levels of AGE. These findings indicate that AGE-dependent modification of the basal lamina induces invasive behaviour...

  9. 9 CFR 3.81 - Environment enhancement to promote psychological well-being.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Environment enhancement to promote..., Treatment, and Transportation of Nonhuman Primates 2 Facilities and Operating Standards § 3.81 Environment..., document, and follow an appropriate plan for environment enhancement adequate to promote the psychological...

  10. "Wer wagt hier Theorie zu fordern": aspects théoriques du timbre chez Arnold Schönberg

    Directory of Open Access Journals (Sweden)

    Frédéric de Buzon

    2014-02-01

    Full Text Available Schönberg’s Harmonielehre finishes on the evocation of the melody of timbre (Klangfarbenmelodie. The aim of this article is to analyse the function of timbre in relation to musical theory by establishing a parallel between the positions expressed by Schönberg and preceding classical positions, namely Jean-Jaques Rousseau’s definition of timbre and Leibniz’s concept of “clear and confused” ideas. Operating in this context, what will be shown is that timbre, according to Leibniz’s description, is a distinguishing, yet undistinguished, quality and that, precisely for this reason, timbre has a limited function in composition.

  11. ANATOMY OF GYNURA AURANTIACA (BLUME) SCH.BIP. EX DC. (ASTERACEAE)

    OpenAIRE

    Rodica BERCU

    2014-01-01

    The paper presents a detailed histoanatomical description, of the vegetative organs (root, stem and leaf) and photographs as well of Gynura aurantiaca (Blume) Sch.Bip. ex DC. It was observed that the root have typical primary dictos structure. The stem has a differentiated in two regions cortex and the stele comprise one ring of open collateral vascular bundles with secondary xylem due to the cambium activity. The petiole anatomy is quite similar in its basic structure with the stem. The blad...

  12. Measles virus antibody responses in children randomly assigned to receive standard-titer edmonston-zagreb measles vaccine at 4.5 and 9 months of age, 9 months of age, or 9 and 18 months of age

    DEFF Research Database (Denmark)

    Martins, Cesario; Garly, May-Lill; Bale, Carlitos

    2014-01-01

    The World Health Organization recommends administration of measles vaccine (MV) at age 9 months in low-income countries. We tested the measles virus antibody response at 4.5, 9, 18, and 24 months of age for children randomly assigned to receive standard-titer Edmonston-Zagreb MV at 4.5 and 9 months...

  13. Critical Age-Dependent Branching Markov Processes and their ...

    Indian Academy of Sciences (India)

    This paper studies: (i) the long-time behaviour of the empirical distribution of age and normalized position of an age-dependent critical branching Markov process conditioned on non-extinction; and (ii) the super-process limit of a sequence of age-dependent critical branching Brownian motions.

  14. Parental acceptability of HPV vaccination for boys and girls aged 9-13 years in China - A population-based study.

    Science.gov (United States)

    Wang, Zixin; Wang, Jingjing; Fang, Yuan; Gross, Danielle L; Wong, Martin C S; Wong, Eliza L Y; Lau, Joseph T F

    2018-05-03

    This study was to investigate parental acceptability of HPV vaccination for their sons and daughters aged 9-13 years under different cost scenarios, and factors associated with parental acceptability at market price. Participants were: (1) Chinese speaking parents aged 18-60 years with a Hong Kong ID card; (2) had a son or a daughter aged 9-13 years at the date of the survey; (3) the child had the right to abode in Hong Kong. Random telephone numbers were selected from up-to-date telephone directories of Hong Kong. A total of 300 eligible parents (boys' parents: 162; girls' parents: 138, response rate: 68.9% & 69%) provided verbal informed consent and completed the anonymous telephone interview during March to October 2016. Using parental acceptability of HPV vaccination at market price as the dependent variable, univariate and multiple logistic regression models were fitted. The prevalence of HPV vaccination was very low among boys and girls (0.6% vs. 2.2%, p = 0.242). Among those whose children had not taken up HPV vaccination, the prevalence of parental acceptability of HPV vaccination for the index son and daughter were: 14.9% and 27.4% (market price), and 51.6% and 63.0% (free vaccination). Adjusted for sociodemographic variables, attitudinal variables based on the Health Belief Model were associated with parental acceptability of HPV vaccination for their sons (perception that it was not worthy, perceived cue to action from mass media and perceived self-efficacy) and for their daughters (perceived susceptibility and perceived severity of HPV infection among females, perceived benefit of HPV vaccination and perceived self-efficacy). Coverage of HPV vaccination among children aged 9-13 years was very low. Instead of waiting for the free universal vaccination to become available, promotion of self-paid HPV vaccination targeting parents is urgently needed. Different strategies should be applied to boys' and girls' parents. Copyright © 2018 Elsevier

  15. Dependence of the estimation of promotional benefits on customer loyalty level

    OpenAIRE

    Pilelienė, Lina; Liesionis, Vytautas

    2009-01-01

    Scientific problem and relevance of the research. The growing usage of sales promotion and loyalty programs elicits interest in and polemics about their effectiveness. Critics argue that sales promotion is not effective, because customers become promotion-dependent. In long term effect of this on market share diminishes. However, other researches provide evidence on the positive effects of sales promotion on sales and revenue. These contradictions highlight the existence of conditions and fac...

  16. Phospholipase A2 activity-dependent and -independent fusogenic activity of Naja nigricollis CMS-9 on zwitterionic and anionic phospholipid vesicles.

    Science.gov (United States)

    Chiou, Yi-Ling; Chen, Ying-Jung; Lin, Shinne-Ren; Chang, Long-Sen

    2011-11-01

    CMS-9, a phospholipase A(2) (PLA(2)) from Naja nigricollis venom, induced the death of human breast cancer MCF-7 cells accompanied with the formation of cell clumps without clear boundaries between cells. Annexin V-FITC staining indicated that abundant phosphatidylserine appeared on the outer membrane of MCF-7 cell clumps, implying the possibility that CMS-9 may promote membrane fusion via anionic phospholipids. To validate this proposition, fusogenic activity of CMS-9 on vesicles composed of zwitterionic phospholipid alone or a combination of zwitterionic and anionic phospholipids was examined. Although CMS-9-induced fusion of zwitterionic phospholipid vesicles depended on PLA(2) activity, CMS-9-induced fusion of vesicles containing anionic phospholipids could occur without the involvement of PLA(2) activity. Membrane-damaging activity of CMS-9 was associated with its fusogenicity. Moreover, CMS-9 induced differently membrane leakage and membrane fusion of vesicles with different compositions. Membrane fluidity and binding capability with phospholipid vesicles were not related to the fusogenicity of CMS-9. However, membrane-bound conformation and mode of CMS-9 depended on phospholipid compositions. Collectively, our data suggest that PLA(2) activity-dependent and -independent fusogenicity of CMS-9 are closely related to its membrane-bound modes and targeted membrane compositions. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. [Henoch-Schönlein Purpura Presenting as Intussusception].

    Science.gov (United States)

    Kim, Keun Young

    2017-06-25

    Henoch-Schönlein purpura (HSP) is systemic vasculitis disease with various clinical manifestations. Gastrointestinal symptoms in patients with HSP are usually common, with an incidence rate of 62-90%. Most of these gastrointestinal symptoms occur after typical skin purpura, which is a very important clinical evidence for making a diagnosis of HSP. It is difficult to diagnose HSP without skin rash. About 25% of patients may experience gastrointestinal symptoms as their first symptoms. Herein, we report a case of ileo-colic intussusception associated with HSP in a 5-years-old girl presented with diffuse abdominal distension. Our patient did present any symptoms of HSP, such as purpura, arthralgia or arthritis, before surgery.

  18. Hormonal status and age differentially affect tolerance to the disruptive effects of delta-9-tetrahydrocannabinol (Δ9-THC on learning in female rats

    Directory of Open Access Journals (Sweden)

    Peter J Winsauer

    2015-07-01

    Full Text Available The effects of hormone status and age on the development of tolerance to D9-THC were assessed in sham-operated (intact or ovariectomized (OVX female rats that received either intraperitoneal saline or 5.6 mg/kg of D9-THC daily from postnatal day (PD 75 to 180 (early adulthood onward or PD 35 to 140 (adolescence onward. During this time, the 4 groups for each age (i.e., intact/saline, intact/THC, OVX/saline, and OVX/THC were trained in a learning and performance procedure and dose-effect curves were established for D9-THC (0.56-56 mg/kg and the cannabinoid type-1 receptor (CB1R antagonist rimonabant (0.32-10 mg/kg. Despite the persistence of small rate-decreasing and error-increasing effects in intact and OVX females from both ages during chronic D9-THC, all of the D9-THC groups developed tolerance. However, the magnitude of tolerance, as well as the effect of hormone status, varied with the age at which chronic D9-THC was initiated. There was no evidence of dependence in any of the groups. Hippocampal protein expression of CB1R, AHA1 (a co-chaperone of CB1R and HSP90β (a molecular chaperone modulated by AHA-1 was affected more by OVX than chronic D9-THC; striatal protein expression was not consistently affected by either manipulation. Hippocampal BDNF expression varied with age, hormone status, and chronic treatment. Thus, hormonal status differentially affects the development of tolerance to the disruptive effects of delta-9-tetrahydrocannabinol (D9-THC on learning and performance behavior in adolescent, but not adult, female rats. These factors and their interactions also differentially affect cannabinoid signaling proteins in the hippocampus and striatum, and ultimately, neural plasticity.

  19. The Piagetian "Schème": A Framework to Study Professional Learning through Conceptualization

    Science.gov (United States)

    Tourmen, Claire; Holgado, Otilia; Métral, Jean-françois; Mayen, Patrick; Olry, Paul

    2017-01-01

    Different theories of learning have been used in vocational education studies and Piaget is a common source of reference. Our intent is to present a specific and original way in which the Piagetian theory of "schèmes" has been developed since the 1990s in studies called "vocational didactics." Developed in French-speaking…

  20. Promoter methylation and age-related downregulation of Klotho in rhesus monkey.

    Science.gov (United States)

    King, Gwendalyn D; Rosene, Douglas L; Abraham, Carmela R

    2012-12-01

    While overall DNA methylation decreases with age, CpG-rich areas of the genome can become hypermethylated. Hypermethylation near transcription start sites typically decreases gene expression. Klotho (KL) is important in numerous age-associated pathways including insulin/IGF1 and Wnt signaling and naturally decreases with age in brain, heart, and liver across species. Brain tissues from young and old rhesus monkeys were used to determine whether epigenetic modification of the KL promoter underlies age-related decreases in mRNA and protein levels of KL. The KL promoter in genomic DNA from brain white matter did not show evidence of oxidation in vivo but did exhibit an increase in methylation with age. Further analysis identified individual CpG motifs across the region of interest with increased methylation in old animals. In vitro methyl modification of these individual cytosine residues confirmed that methylation of the promoter can decrease gene transcription. These results provide evidence that changes in KL gene expression with age may, at least in part, be the result of epigenetic changes to the 5' regulatory region.

  1. schématisation de la relativité générale , tenseurs et relativité restreinte

    OpenAIRE

    Chabbi , Noureddine

    2018-01-01

    Ce travail qui s'intitule ''schématisation de la relativité générale , tenseurs et relativité restreinte '' prolonge et continue un précédant : '' schématisation de la relativité générale , espace-temps et gravitation '' paru sur ce site sous la référence 01337506 en date du 27/06/2016.L'attention est portée cette fois ci sur 2 autres supports de la théorie de la relativité générale, à savoir '' les tenseurs '' et '' la relativité restreinte ''.L'espace-temps courbe a été expliqué par la géom...

  2. Age dependent radiation sensitivity of eggs of Dysdercus koenigii Fabricius

    International Nuclear Information System (INIS)

    Harwalkar, M.R.

    1992-01-01

    Eggs of Dysdercus koenigii Fabricius aged 0 to 2, 24, 48 and 72 hr were irradiated with X-ray doses ranging between 3 to 15 Gy to determine radiation sensitivity. It was observed that age of the eggs greatly influenced their response to radiation treatment. A dose of 6 Gy was required to prevent hatching of 0 to 2 hr old eggs but older eggs (24 and 48 hr) required 9 and 15 Gy, respectively, to bring about the same effect. At all the doses hatchability of 72 hr old irradiated eggs was much higher than those irradiated at younger age. Survival of nymphs emerging from 72 hr irradiated eggs at different dose levels was found to be dose dependent. Percentage of nymphs metamorphosing into adults decreased with increasing radiation dose received at the embryonic stage. (author). 21 refs., 2 figs

  3. Effectiveness of the Vital Aging program to promote active aging in Mexican older adults

    Directory of Open Access Journals (Sweden)

    Mendoza-Ruvalcaba NM

    2016-11-01

    Full Text Available Neyda Ma Mendoza-Ruvalcaba,1 Rocío Fernández-Ballesteros2 1Health Sciences Department, University of Guadalajara, University Center of Tonalá, Tonalá, Jalisco, Mexico; 2Department of Biological and Health Psychology, Autonomous University of Madrid, Madrid, Spain Introduction: Aging is not only a population phenomenon but also an experience and an individual reality. Vital Aging® is a program that considers active aging as the lifelong adaptation process of maximizing health and independence, physical and cognitive functioning, positive affect regulation and control, and social engagement. Through its different versions and editions, it has demonstrated being an effective program to promote active aging. The aim of this study is to determine the effectiveness of the “face-to-face” and “combined” versions of the program to promote active aging in Mexican older adults trial. Methods: Seventy-six older adults aged 60 years and over participated in a quasi-experimental study and were recruited in a senior center to participate in the two experimental conditions: Vital Aging face-to-face (VA-FF (n=35 and Vital Aging combined (VA-C; multimedia/face-to-face (n=15, and the remaining 26 adults were assigned to a control group. Pretest and posttest assessments were performed after the theoretical–practical intervention. Mean differences and size effects were calculated for estimating the effect of the program. Results: At the end of the study, participants showed improvements in the active aging outcome measures. Positive effects were observed in the frequency of intellectual, cultural – artistic, and social activities, perceptions of aging, satisfaction with social relationships, and self-efficacy for aging. Additionally, those who participated in VA-FF showed better memory performance, meta-memory, and a trend to report less memory problems, while older persons in VA-C showed a trend to have better life satisfaction. No effects were

  4. The European saber-toothed cat (Homotherium latidens) found in the "Spear Horizon" at Schöningen (Germany).

    Science.gov (United States)

    Serangeli, Jordi; Van Kolfschoten, Thijs; Starkovich, Britt M; Verheijen, Ivo

    2015-12-01

    The 300,000 year old Lower Paleolithic site Schöningen 13 II-4 became world famous with the discovery of the oldest well-preserved and complete wooden spears. Through ongoing excavations, new archaeological discoveries of scientific importance are still being made from the same archaeological layer where the spears were found. In this context, remains of a rare carnivore species, the European saber-toothed cat (Homotherium latidens), were recovered. Here we present five teeth and one humerus fragment that are unambiguously from two individual saber-toothed cats. The humerus is a unique specimen; it shows evidence of hominin impacts and use as a percussor. The Homotherium remains from Schöningen are the best documented finds of this species in an archaeological setting and they are amongst the youngest specimens of Homotherium in Europe. The presence of this species as a carnivore competitor would certainly have impacted the lives of late Middle Pleistocene hominins. The discovery illustrates the possible day-to-day challenges that the Schöningen hominins would have faced and suggests that the wooden spears were not necessarily only used for hunting, but possibly also as a weapon for self-defense. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Longitudinal study of microvascular involvement by nailfold capillaroscopy in children with Henoch-Schönlein purpura.

    Science.gov (United States)

    Zampetti, Anna; Rigante, Donato; Bersani, Giulia; Rendeli, Claudia; Feliciani, Claudio; Stabile, Achille

    2009-09-01

    The aim of this study is to describe by video-nailfold capillaroscopy the microvascular involvement and capillary changes in children with Henoch-Schönlein purpura (HSp) and to establish a possible correlation with clinical outcome. Thirty-one patients underwent capillaroscopic evaluation through a videomicroscope during the acute phase and after 6 months. Twenty sex/age-matched controls were also examined. All capillaroscopic variables were statistically examined in combination with laboratoristic/clinical data. Architectural and morphological changes recorded during the acute phase were statistically significant in comparison to the controls (p capillaroscopy changes, laboratoristic/clinical data, and outcome. Video-nailfold capillaroscopy can be a simple tool to evaluate microvascular abnormalities in the acute phase of HSp, and the persistence of oedema could suggest an incomplete disease resolution at a microvascular level.

  6. Henoch-Schönlein purpura in an older man presenting as rectal bleeding and IgA mesangioproliferative glomerulonephritis: a case report

    OpenAIRE

    Howarth Charles B; Jirajariyavej Teeranun; Cheungpasitporn Wisit; Rosen Raquel M

    2011-01-01

    Abstract Introduction Henoch-Schönlein purpura is the most common systemic vasculitis in children. Typical presentations are palpable purpura, abdominal pain, arthritis, and hematuria. This vasculitic syndrome can present as an uncommon cause of rectal bleeding in older patients. We report a case of an older man with Henoch-Schönlein purpura. He presented with rectal bleeding and acute kidney injury secondary to IgA mesangioproliferative glomerulonephritis. Case presentation A 75-year-old Pol...

  7. Healthy Aging Promotion through Neuroscientific Information-Based Strategies.

    Science.gov (United States)

    Seinfeld, Sofia; Sanchez-Vives, Maria V

    2015-09-28

    To ensure the well-being of a rapidly growing elderly population, it is fundamental to find strategies to foster healthy brain aging. With this intention, we designed a program of scientific-based lectures aimed at dissemination by established neuroscientists about brain function, brain plasticity and how lifestyle influences the brain. We also carried out a pilot study on the impact of the lectures on attendees. The objective was to provide information to elderly people in order to encourage them to identify unhealthy and healthy daily habits, and more importantly, to promote behavioral changes towards healthy brain aging. Here we report on our experience. In order to determine the impact of the lectures in the daily routine of the attendees, we asked them to fill out questionnaires. Preliminary results indicate that neuroscientific information-based strategies can be a useful method to have a positive impact on the lives of elderly, increase their awareness on how to improve brain function and promote positive lifestyle modifications. Furthermore, based on self-reported data, we also found that through this strategy it is possible to promote behavioral changes related to nutrition, sleep, and realization of physical and cognitively stimulating activities. Finally, based on the results obtained, the importance of promoting self-efficacy and the empowerment of the older populations is highlighted.

  8. Healthy Aging Promotion through Neuroscientific Information-Based Strategies

    Directory of Open Access Journals (Sweden)

    Sofia Seinfeld

    2015-09-01

    Full Text Available To ensure the well-being of a rapidly growing elderly population, it is fundamental to find strategies to foster healthy brain aging. With this intention, we designed a program of scientific-based lectures aimed at dissemination by established neuroscientists about brain function, brain plasticity and how lifestyle influences the brain. We also carried out a pilot study on the impact of the lectures on attendees. The objective was to provide information to elderly people in order to encourage them to identify unhealthy and healthy daily habits, and more importantly, to promote behavioral changes towards healthy brain aging. Here we report on our experience. In order to determine the impact of the lectures in the daily routine of the attendees, we asked them to fill out questionnaires. Preliminary results indicate that neuroscientific information-based strategies can be a useful method to have a positive impact on the lives of elderly, increase their awareness on how to improve brain function and promote positive lifestyle modifications. Furthermore, based on self-reported data, we also found that through this strategy it is possible to promote behavioral changes related to nutrition, sleep, and realization of physical and cognitively stimulating activities. Finally, based on the results obtained, the importance of promoting self-efficacy and the empowerment of the older populations is highlighted.

  9. Henoch-Schönlein Purpura Complicated by Hepatocellular Carcinoma.

    Science.gov (United States)

    Akizue, Naoki; Suzuki, Eiichiro; Yokoyama, Masayuki; Inoue, Masanori; Wakamatsu, Toru; Saito, Tomoko; Kusakabe, Yuko; Ogasawara, Sadahisa; Ooka, Yoshihiko; Tawada, Akinobu; Maru, Yugo; Matsue, Hiroyuki; Chiba, Tetsuhiro

    2017-11-15

    Although Henoch-Schönlein purpura (HSP) is known to be accompanied by malignancies, cases with hepatobiliary cancer are extremely rare. A 62-year-old man with palpable purpura rapidly extending to both lower legs was admitted to our hospital. He was undergoing follow-up for cirrhosis caused by chronic hepatitis B virus infection and hepatocellular carcinoma (HCC). He had renal dysfunction with hematuria and proteinuria and abdominal pain. Based on the clinical presentation and skin biopsy findings, he was diagnosed with HSP. The administration of steroids resulted in the rapid improvement of the patient's symptoms and he was discharged 12 days after admission.

  10. Henoch-schönlein purpura (HSP) in an adult

    Science.gov (United States)

    Negara, C. A.; Zubir, Z.

    2018-03-01

    Henoch-schönlein purpura (HSP) is vasculitis of the small vessels, the most common vasculitis of the childhood and is uncommon in adults. A case of HSP is reported in a 36-year-old female with ten days history of multiple palpable purpura on region antebrachii, region femoralis and cruris dextra et sinistra. Burn sensation in both legs, pain sensation on knees joint and ankles joint and bloody stools were found. History of a cough and sore throat are often to be a presentation. Laboratory examination was mild anemia, mild leukocytes, ASTO (antistreptolysin titer O): children due to an increased risk of disorders of the renal.

  11. EPICOG-SCH: A brief battery to screen cognitive impact of schizophrenia in stable outpatients

    Directory of Open Access Journals (Sweden)

    Silvia Zaragoza Domingo

    2017-06-01

    The EPICOG-SCH proved to be a useful brief tool to screen for the cognitive impact of schizophrenia, and its regression-weighted Composite Score was an efficient complement to clinical interviews for confirming patients' potential functional outcomes and can be useful for monitoring cognition during routine outpatient follow-up visits.

  12. Von der Geschäftsidee zum Businessplan Businessplan für Schülerunternehmen

    NARCIS (Netherlands)

    Prof. Dr. Ingo Bieberstein; Dr. Ulrich Scholz

    2011-01-01

    Das Buch gibt einen Einblick in die Grundlagen der Betriebswirtschaftslehre und will das Verständnis für ökonomische Zusammenhänge fördern. Das Buch gibt eine Anleitung zur Erstellung eines Businessplans mit vielen praktischen Beispielen. Die Zielgruppe dieses Buches sind Schüler, aber auch

  13. A cII-dependent promoter is located within the Q gene of bacteriophage lambda.

    OpenAIRE

    Hoopes, B C; McClure, W R

    1985-01-01

    We have found a cII-dependent promoter, PaQ, within the Q gene of bacteriophage lambda. Transcription experiments and abortive initiation assays performed in vitro showed that the promoter strength and the cII affinity of PaQ were comparable to the other cII-dependent lambda promoters, PE and PI. The location and leftward direction of PaQ suggests a possible role in the delay of lambda late-gene expression by cII protein, a phenomenon that has been called cII-dependent inhibition. We have con...

  14. 9Th Injury Prevention and Safety Promotion Conference, Melbourne ...

    African Journals Online (AJOL)

    Test

    The 9th Injury Prevention and Safety Promotion Conference was held in Melbourne,. Australia, from 24 to 26 July 2009. This conference formed part of a series of conferences initiated in 1993 by the Monash University's Accident Research Centre (MOARC) in partnership ... outputs in injury presentation work. The speaker ...

  15. Bone and heart abnormalities of subclinical hyperthyroidism in women below the age of 65 years

    OpenAIRE

    Rosario, Pedro Weslley

    2008-01-01

    The objective of the present study was to evaluate bone and cardiac abnormalities and symptoms and signs of thyroid hormone excess in women with subclinical hyperthyroidism (SCH) aged < 65 years. Forty-eight women with SCH were evaluated. The control group consisted of 48 euthyroid volunteers. The mean symptom rating scale score was significantly higher in patients. Cardiac involvement, both morphological and affecting systolic and diastolic functions, was also observed in patients. Women wit...

  16. Community Nurses' Experiences Regarding the Meaning and Promotion of Healthy Aging in Northeastern Thailand.

    Science.gov (United States)

    Manasatchakun, Pornpun; Choowattanapakorn, Tassana; Roxberg, Åsa; Asp, Margareta

    2018-03-01

    Describe community nurses' experiences regarding the meaning and promotion of healthy aging in northeastern Thailand. Data were collected through five focus group interviews with 36 community nurses in northeastern Thailand. Latent content analysis was conducted to analyze the data. Healthy aging was characterized by the interconnection of older persons, older persons' family members, and the community. Healthy aging was associated with two themes: "being strong" and "being a supporter and feeling supported." The nurses' experiences in promoting healthy aging were described by the themes "providing health assessment," "sharing knowledge," and "having limited resources." The findings of this study provide a deeper understanding of the meaning of healthy aging from a holistic viewpoint. Community nurses must pay attention to older persons and their surroundings when planning how to promote healthy aging. Person-centeredness should be applied in practice to promote healthy aging. The current findings contribute useful information that should help policy makers develop healthy aging strategies in Thailand.

  17. Age-dependent complex noise fluctuations in the brain

    International Nuclear Information System (INIS)

    Mareš, Jan; Vyšata, Oldřich; Procházka, Aleš; Vališ, Martin

    2013-01-01

    We investigated the parameters of colored noise in EEG data of 17 722 professional drivers aged 18–70. The whole study is based upon experiments showing that biological neural networks may operate in the vicinity of the critical point and that the balance between excitation and inhibition in the human brain is important for the transfer of information. This paper is devoted to the study of EEG power spectrum which can be described best by a power function with 1/f λ distribution and colored noise corresponding to the critical point in the EEG signal has the value of λ = 1 (purple noise). The slow accumulation of energy and its quick release is a universal property of the 1/f distribution. The physiological mechanism causing energy dissipation in the brain seems to depend on the number and strength of the connections between clusters of neurons. With ageing, the number of connections between the neurons decreases. Learning ability and intellectual performance also decrease. Therefore, age-related changes in the λ coefficient can be anticipated. We found that absolute values of λ coefficients decrease significantly with increasing age. Deviations from this rule are related to age-dependent slowing of the dominant frequency in the alpha band. Age-dependent change in the parameter and colored noise may be indicative of age-related changes in the self-organization of brain activity. Results obtained include (i) the age-dependent decrease of the absolute values of the average λ coefficient with the regression coefficient 0.005 1/year, (ii) distribution of λ value changes related to EEG frequency bands and to localization of electrodes on the scalp, and (iii) relation of age-dependent changes of colored noise and EEG energy in separate frequency bands. (paper)

  18. Cultivating Social Work Leadership in Health Promotion and Aging: Strategies for Active Aging Interventions

    Science.gov (United States)

    Marshall, Victor W.; Altpeter, Mary

    2005-01-01

    The rapid growth of the population of older adults and their concomitant physical status and health needs have captured the attention, collaboration, and funding support of an array of leaders in the fields of aging and health care. To help fill the void of literature available to social workers interested in health promotion and aging, the…

  19. Alfred Schütz’s writings from the perspective of a theory of action’s creativity

    Directory of Open Access Journals (Sweden)

    Javier L. Cristiano

    2013-06-01

    Full Text Available The article proposes a review of the work of Schütz from the question about “creativity” of social action, which was not made expressly by the author but it is in his writings an important principle of response. After positioning the subject in some coordinates of the current sociological discussion, we present four specific fields from schütz’ contributions: the ability to expand and make a creative use of “the social heritage of knowledge”, the individual and collective capacity to imagine action projects, the ability to create and use symbols, and producing with them exclusive worlds of imaginary existence, as well as the ability to give birth to new experiences. It is stated that these four fields outline the contours of a phenomenology of creativity of action, which sets out some open fields for further research.

  20. Dual effects of N-acetyl-L-cysteine dependent on NQO1 activity: Suppressive or promotive of 9,10-phenanthrenequinone-induced toxicity

    International Nuclear Information System (INIS)

    Toyooka, Tatsushi; Shinmen, Takuya; Aarts, Jac M.M.J.G.; Ibuki, Yuko

    2012-01-01

    A typical antioxidant, N-acetyl-L-cysteine (NAC) generally protects cells from oxidative damage induced by reactive oxygen species (ROS). 9,10-Phenanthrenequinone (9,10-PQ), a major quinone in diesel exhaust particles, produces ROS in redox cycling following two-electron reduction by NAD(P)H:quinone oxidoreductase 1 (NQO1), which has been considered as a cause of its cyto- and genotoxicity. In this study, we show that NAC unexpectedly augments the toxicity of 9,10-PQ in cells with low NQO1 activity. In four human skin cell lines, the expression and the activity of NQO1 were lower than in human adenocarcinoma cell lines, A549 and MCF7. In the skin cells, the cytotoxicity of 9,10-PQ was significantly enhanced by addition of NAC. The formation of DNA double strand breaks accompanying phosphorylation of histone H2AX, was also remarkably augmented. On the other hand, the cyto- and genotoxicity were suppressed by addition of NAC in the adenocarcinoma cells. Two contrasting experiments: overexpression of NQO1 in CHO-K1 cells which originally expressed low NQO1 levels, and knock‐down of NQO1 in the adenocarcinoma cell line A549 by transfection of RNAi, also showed that NAC suppressed 9,10-PQ-induced toxicity in cell lines expressing high NQO1 activity and enhanced it in cell lines with low NQO1 activity. The results suggested that dual effects of NAC on the cyto- and genotoxicity of 9,10-PQ were dependent on tissue-specific NQO1 activity. -- Highlights: ► NAC augmented the cytotoxicity of 9,10-PQ in skin cell lines. ► 9,10-PQ-induced DSBs accompanying γ-H2AX were also augmented by NAC. ► NAC suppressed the cyto- and genotoxicity of 9,10-PQ in adenocarcinoma cell lines. ► The dual effects of NAC on toxicity of 9,10-PQ were dependent on NQO1 activity.

  1. The promoter of the Arabidopsis thaliana plastocyanin gene contains a far upstream enhancer-like element involved in chloroplast-dependent expression.

    Science.gov (United States)

    Vorst, O; Kock, P; Lever, A; Weterings, B; Weisbeek, P; Smeekens, S

    1993-12-01

    Plastocyanin is part of the photosynthetic electron transport chain in the chloroplast and is encoded in the nucleus. Expression of the Arabidopsis thaliana plastocyanin gene is organ specific: high mRNA levels are observed in young green parts of the plant. Furthermore, expression is dependent on the presence of light and functional chloroplasts. When grown in the presence of norflurazon under white light conditions, resulting in the photo-oxidative destruction of the chloroplast, plastocyanin mRNA levels are strongly reduced. A -1579 to -9 promoter fragment confers light-regulated and chloroplast-dependent expression to the beta-glucuronidase reporter gene in transgenic tobacco plants. This suggests that regulation takes place at the level of transcription. A plastocyanin promoter deletion series ranging from -1579 to -121 which was also tested in tobacco, revealed the presence of a strong positive regulating element (PRE) in the -1579 to -705 region. Deletion of this part of the promoter resulted in a approximately 100-fold reduction of GUS expression as measured in mature leaves. Surprisingly, this enhancer-like element was capable of stimulating transcription from a position downstream of its reporter. Moreover, it could also activate a truncated CaMV 35S promoter. Deletion of this element coincides with the loss of chloroplast-dependency of reporter gene expression, as judged by norflurazon treatment of transgenic seedlings. So, the activity of the PRE itself might depend on the presence of functional chloroplasts.

  2. Nina Degele: Gender/Queer Studies. München: UTB Fink 2008. — Franziska Schößler: Einführung in die Gender Studies. Berlin: Akademie Verlag 2008

    Directory of Open Access Journals (Sweden)

    Heike Kahlert

    2009-03-01

    Full Text Available Nina Degele und Franziska Schößler treiben mit ihren Einführungsbüchern in die Gender Studies beziehungsweise in die Gender/Queer Studies die Disziplinierung dieser neuen Wissensfelder voran. Ausgehend von ihren jeweiligen Herkunftsdisziplinen (Soziologie und Literaturwissenschaft legen sie übersichtliche Überblicke vor, die explizit für die Hochschullehre konzipiert sind. Beide Bücher leisten einen wichtigen Beitrag zur Kanonisierung der Gender Studies als akademisches Fach, bleiben aber in ihrer Konzeption stark den Herkunftsdisziplinen ihrer Verfasserinnen verhaftet. Hier stößt die viel beschworene Interdisziplinarität der Gender Studies an ihre Grenzen.Nina Degele and Franziska Schößler promote the disciplinary establishment of new fields of knowledge with their introductory books in Gender Studies and Gender/Queer Studies. Using their individual home disciplines (sociology and literary studies as a starting point, they present clear overviews of these new fields of knowledge explicitly conceived for use in higher education. Both books contribute to the canonization of Gender Studies as an academic discipline, however they remain in their conception strongly attached to the home disciplines of their authors. It is here that the often-touted interdisciplinarity of Gender Studies reaches its limits.

  3. On 18 December 2004, the President of the Swiss Electro-technical Committee, Martin Reichle (left), presented the award to Helmut Schönbacher.

    CERN Multimedia

    2005-01-01

    Helmut Schönbacher, previously of CERN's Safety Commission, has received the 1906 Award of the International Electrotechnical Commission (IEC) for his standardization work on the influence of ionizing radiation on insulating materials. From 1986 until 2004, Schönbacher led a working group on radiation composed of internationally recognized experts, which edited standards in the IEC 60544 series on the determination of the effects of ionizing radiation on electrically insulating materials.

  4. Identifying transportation solutions that promote healthy aging for Texas : final report.

    Science.gov (United States)

    2017-09-01

    As the population of Texans who are aging continues to grow, the role that transportation plays in the promotion of healthy aging is useful information for policy makers to plan and provide for the safe and healthy aging of Texass population. Tran...

  5. TNF-α promotes human retinal pigment epithelial (RPE) cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression through activation of Akt/mTORC1 signaling

    International Nuclear Information System (INIS)

    Wang, Cheng-hu; Cao, Guo-Fan; Jiang, Qin; Yao, Jin

    2012-01-01

    Highlights: ► TNF-α induces MMP-9 expression and secretion to promote RPE cell migration. ► MAPK activation is not critical for TNF-α-induced MMP-9 expression. ► Akt and mTORC1 signaling mediate TNF-α-induced MMP-9 expression. ► SIN1 knockdown showed no significant effect on MMP-9 expression by TNF-α. -- Abstract: Tumor necrosis factor-alpha (TNF-α) promotes in vitro retinal pigment epithelial (RPE) cell migration to initiate proliferative vitreoretinopathy (PVR). Here we report that TNF-α promotes human RPE cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression. Inhibition of MMP-9 by its inhibitor or its neutralizing antibody inhibited TNF-α-induced in vitro RPE cell migration. Reversely, exogenously-added active MMP-9 promoted RPE cell migration. Suppression Akt/mTOR complex 1(mTORC1) activation by LY 294002 and rapamycin inhibited TNF-α-mediated MMP-9 expression. To introduce a constitutively active Akt (CA-Akt) in cultured RPE cells increased MMP-9 expression, and to block mTORC1 activation by rapamycin inhibited its effect. RNA interference (RNAi)-mediated silencing of SIN1, a key component of mTOR complex 2 (mTORC2), had no effect on MMP-9 expression or secretion. In conclusion, this study suggest that TNF-α promotes RPE cell migration by inducing MMP-9 expression through activation of Akt/ mTORC1, but not mTORC2 signaling.

  6. TNF-{alpha} promotes human retinal pigment epithelial (RPE) cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression through activation of Akt/mTORC1 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Cheng-hu; Cao, Guo-Fan [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China); Jiang, Qin, E-mail: Jqin710@vip.sina.com [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China); Yao, Jin, E-mail: dryaojin@yahoo.com [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China)

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer TNF-{alpha} induces MMP-9 expression and secretion to promote RPE cell migration. Black-Right-Pointing-Pointer MAPK activation is not critical for TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer Akt and mTORC1 signaling mediate TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer SIN1 knockdown showed no significant effect on MMP-9 expression by TNF-{alpha}. -- Abstract: Tumor necrosis factor-alpha (TNF-{alpha}) promotes in vitro retinal pigment epithelial (RPE) cell migration to initiate proliferative vitreoretinopathy (PVR). Here we report that TNF-{alpha} promotes human RPE cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression. Inhibition of MMP-9 by its inhibitor or its neutralizing antibody inhibited TNF-{alpha}-induced in vitro RPE cell migration. Reversely, exogenously-added active MMP-9 promoted RPE cell migration. Suppression Akt/mTOR complex 1(mTORC1) activation by LY 294002 and rapamycin inhibited TNF-{alpha}-mediated MMP-9 expression. To introduce a constitutively active Akt (CA-Akt) in cultured RPE cells increased MMP-9 expression, and to block mTORC1 activation by rapamycin inhibited its effect. RNA interference (RNAi)-mediated silencing of SIN1, a key component of mTOR complex 2 (mTORC2), had no effect on MMP-9 expression or secretion. In conclusion, this study suggest that TNF-{alpha} promotes RPE cell migration by inducing MMP-9 expression through activation of Akt/ mTORC1, but not mTORC2 signaling.

  7. Physical Fitness Percentiles of German Children Aged 9-12 Years: Findings from a Longitudinal Study.

    Directory of Open Access Journals (Sweden)

    Kathleen Golle

    Full Text Available Generating percentile values is helpful for the identification of children with specific fitness characteristics (i.e., low or high fitness level to set appropriate fitness goals (i.e., fitness/health promotion and/or long-term youth athlete development. Thus, the aim of this longitudinal study was to assess physical fitness development in healthy children aged 9-12 years and to compute sex- and age-specific percentile values.Two-hundred and forty children (88 girls, 152 boys participated in this study and were tested for their physical fitness. Physical fitness was assessed using the 50-m sprint test (i.e., speed, the 1-kg ball push test, the triple hop test (i.e., upper- and lower- extremity muscular power, the stand-and-reach test (i.e., flexibility, the star run test (i.e., agility, and the 9-min run test (i.e., endurance. Age- and sex-specific percentile values (i.e., P10 to P90 were generated using the Lambda, Mu, and Sigma method. Adjusted (for change in body weight, height, and baseline performance age- and sex-differences as well as the interactions thereof were expressed by calculating effect sizes (Cohen's d.Significant main effects of Age were detected for all physical fitness tests (d = 0.40-1.34, whereas significant main effects of Sex were found for upper-extremity muscular power (d = 0.55, flexibility (d = 0.81, agility (d = 0.44, and endurance (d = 0.32 only. Further, significant Sex by Age interactions were observed for upper-extremity muscular power (d = 0.36, flexibility (d = 0.61, and agility (d = 0.27 in favor of girls. Both, linear and curvilinear shaped curves were found for percentile values across the fitness tests. Accelerated (curvilinear improvements were observed for upper-extremity muscular power (boys: 10-11 yrs; girls: 9-11 yrs, agility (boys: 9-10 yrs; girls: 9-11 yrs, and endurance (boys: 9-10 yrs; girls: 9-10 yrs. Tabulated percentiles for the 9-min run test indicated that running distances between 1

  8. Age-dependent mixing of deep-sea sediments

    International Nuclear Information System (INIS)

    Smith, C.R.; Maggaard, L.; Pope, R.H.; DeMaster, D.J.

    1993-01-01

    Rates of bioturbation measured in deep-sea sediments commonly are tracer dependent; in particular, shorter lived radiotracers (such as 234 Th) often yield markedly higher diffusive mixing coefficients than their longer-lived counterparts (e.g., 210 Pb). At a single station in the 1,240-m deep Santa Catalina Basin, the authors document a strong negative correlation between bioturbation rate and tracer half-life. Sediment profiles of 234 Th (half-life = 24 days) yield an average mixing coefficient (60 cm 2 y -1 ) two orders of magnitude greater than that for 210 Pb (half-life = 22 y, mean mixing coefficient = 0.4 cm 2 y -1 ). A similar negative relationship between mixing rate and tracer time scale is observed at thirteen other deep-sea sites in which multiple radiotracers have been used to assess diffusive mixing rates. This relationship holds across a variety of radiotracer types and time scales. The authors hypothesize that this negative relationship results from age-dependent mixing, a process in which recently sedimented, food-rich particles are ingested and mixed at higher rates by deposit feeders than are older, food-poor particles. Results from an age-dependent mixing model demonstrate that this process indeed can yield the bioturbation-rate vs. tracer-time-scale correlations observed in deep-sea sediments. Field data on mixing rates of recently sedimented particles, as well as the radiotracer activity of deep-sea deposit feeders, provide strong support for the age-dependent mixing model. The presence of age-dependent mixing in deep-sea sediments may have major implications for diagenetic modeling, requiring a match between the characteristic time scales of mixing tracers and modeled reactants. 102 refs., 6 figs., 5 tabs

  9. Katrin Schütz: Geschlechterentwürfe im literarischen Werk von Lou Andreas-Salomé unter Berücksichtigung ihrer Geschlechtertheorie. Würzburg: Verlag Königshausen & Neumann 2008

    Directory of Open Access Journals (Sweden)

    Romana Weiershausen

    2009-03-01

    Full Text Available Katrin Schütz hat eine Studie zu Geschlechterkonzeptionen in Lou Andreas-Salomés Frühwerk vorgelegt, in der auch die bislang wenig berücksichtigten literarischen Texte der Autorin ausgewertet werden. Die Anlage zielt auf eine Überblicksdarstellung, hinter der die differenzierende Reflexion der einzelnen Thesen zurück steht: Schütz geht es um die Konturierung einer Typologie. Durch die erweiterte Textgrundlage wird dabei Neues erschlossen, woraus sich anregende Impulse für die Jahrhundertwende-Forschung ergeben.Katrin Schütz’s study of gender conceptions in Lou Andreas-Salomé’s early work considers those literary texts often ignored by scholarship. The study is constructed as an overview, in light of which a differentiated reflection on the individual theses falls short: Schütz intends to formulate a typology. The expanded textual basis allows for the creation of something new, which will in turn provide inspirational impulses for turn-of-the-century research.

  10. Risk Factors Associated with Renal Involvement in Childhood Henoch-Schönlein Purpura: A Meta-Analysis

    Science.gov (United States)

    Chan, Han; Tang, Yan-Ling; Lv, Xiao-Hang; Zhang, Gao-Fu; Wang, Mo; Yang, Hai-Ping; Li, Qiu

    2016-01-01

    Background and objective Henoch-Schönlein purpura (HSP) is an important cause of chronic kidney disease in children. This meta-analysis identified risk factors associated with renal involvement in childhood HSP. Methods PubMed, Embase, and Web of Science were searched. The quality of all eligible studies was assessed using the Newcastle-Ottawa scale criteria. An analysis of possible risk factors was conducted to report the odds ratio (OR) and weighted mean difference (WMD). Results Thirteen studies (2398 children) revealed 20 possible and 13 significant risk factors associated with renal involvement in HSP, with the following meta-analysis estimates of OR and WMD, with 95% confidence intervals: older age (0.90, 0.61–1.19); age > 10 y (3.13, 1.39–7.07); male gender (1.36, 1.07–1.74); abdominal pain (1.94,1.24–3.04); gastrointestinal bleeding (1.86, 1.30–2.65); severe bowel angina (3.38, 1.17–9.80); persistent purpura (4.02, 1.22–13.25); relapse (4.70, 2.42–9.14); WBC > 15 × 109/L (2.42, 1.39–4.22); platelets > 500 × 109/L (2.98, 1.22–7.25); elevated antistreptolysin O (ASO) (2.17, 1.29–3.64); and decreased complement component 3 (C3) (3.13, 1.62–6.05). Factors not significantly associated with renal involvement were: blood pressure; orchitis; elevated C-reactive protein; elevated erythrocyte sedimentation rate (ESR); and elevated serum IgA/IgE or IgG. Arthritis/arthralgia may be a risk factor according to the criteria of the American College of Rheumatology (1.41, 1.01–1.96). Conclusion The following are associated with renal involvement in pediatric HSP: male gender; > 10 y old; severe gastrointestinal symptoms (abdominal pain, gastrointestinal bleeding, and severe bowel angina); arthritis/arthralgia; persistent purpura or relapse; WBC > 15 × 109/L; platelets > 500 × 109/L; elevated ASO; and low C3. Relevant clinical interventions for these risk factors may exert positive effects on the prevention of kidney disease during the early

  11. 42 CFR 61.9 - Payments: Stipends; dependency allowances; travel allowances.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Payments: Stipends; dependency allowances; travel... FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.9 Payments: Stipends; dependency allowances; travel allowances. Payments for stipends, dependency allowances, and the travel allowances...

  12. Nickel detoxification and plant growth promotion by multi metal resistant plant growth promoting Rhizobium species RL9.

    Science.gov (United States)

    Wani, Parvaze Ahmad; Khan, Mohammad Saghir

    2013-07-01

    Pollution of the biosphere by heavy metals is a global threat that has accelerated dramatically since the beginning of industrial revolution. The aim of the study is to check the resistance of RL9 towards the metals and to observe the effect of Rhizobium species on growth, pigment content, protein and nickel uptake by lentil in the presence and absence of nickel. The multi metal tolerant and plant growth promoting Rhizobium strain RL9 was isolated from the nodules of lentil. The strain not only tolerated nickel but was also tolerant o cadmium, chromium, nickel, lead, zinc and copper. The strain tolerated nickel 500 μg/mL, cadmium 300 μg/mL, chromium 400 μg/mL, lead 1,400 μg/mL, zinc 1,000 μg/mL and copper 300 μg/mL, produced good amount of indole acetic acid and was also positive for siderophore, hydrogen cyanide and ammonia. The strain RL9 was further assessed with increasing concentrations of nickel when lentil was used as a test crop. The strain RL9 significantly increased growth, nodulation, chlorophyll, leghaemoglobin, nitrogen content, seed protein and seed yield compared to plants grown in the absence of bioinoculant but amended with nickel The strain RL9 decreased uptake of nickel in lentil compared to plants grown in the absence of bio-inoculant. Due to these intrinsic abilities strain RL9 could be utilized for growth promotion as well as for the remediation of nickel in nickel contaminated soil.

  13. Des schémas équivalents pour les circuits couplés multi-enroulements

    Science.gov (United States)

    Keradec, J. P.; Cogitore, B.; Laveuve, E.; Bensoam, M.

    1994-04-01

    The aim of this paper is to represent the electrical behaviour of any number of magnetically coupled windings with couplers and inductors. Two methods, mathematicaly justified, are proposed. The second one introduces only positive inductances. As an exemple, it is applied to the representation of a three column three phase transformer. The obtained circuits supply the requisite guide to design more complete circuits which allow the high frequency behaviour of wound components to be taken into account, especialy in electronics simulation softwares. Le but de cet article est de traduire le comportement électrique d'un nombre quelconque d'enroulements magnétiquement couplés, par des coupleurs et des inductances. Deux méthodes, établies mathématiquement, sont proposées. La seconde n'introduit que des inductances positives. A titre d'exemple, elle est appliquée à la représentation d'un transformateur triphasé à trois colonnes. Les schémas obtenus fournissent l'indispensable ossature de schémas plus complets, aptes à représenter le comportement haute fréquence des composants bobinés, notamment dans un logiciel de simulation électronique.

  14. Chemical Composition of the Essential Oils of the Flowers, Leaves and Stems of Two Senecio polyanthemoides Sch. Bip. Samples from South Africa

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    Lawal A. Oladipupo

    2009-06-01

    Full Text Available The essential oils of the flowers, leaves and stems of Senecio polyanthemoides Sch. Bip. Samples collected from two different localities within the city of uMhlathuze, KwaZulu-Natal Province (South Africa were isolated by hydrodistillation and analyzed using GC and GC/MS. Twenty-six constituents were identified, representing an average of 86.0 - 99.6% of the total oil composition. The chemical profile reveals the dominance of monoterpenoid compounds, although some quantitative variance was noticed. The main constituents of the oils were limonene (3.1 – 43.0%, p-cymene (4.9-36.3%, β-selinene (1.3-32.7%, α-pinene (1.8-21.4%, β-pinene (7.6-16.5% and 1,8-cineole (9.3-11.4%, caryophyllene oxide (4.1-13.4% and humulene epoxide II (8.6-10.3%.

  15. Teacher led school-based surveillance can allow accurate tracking of emerging infectious diseases - evidence from serial cross-sectional surveys of febrile respiratory illness during the H1N1 2009 influenza pandemic in Singapore

    Directory of Open Access Journals (Sweden)

    Soh Shu E

    2012-12-01

    Full Text Available Abstract Background Schools are important foci of influenza transmission and potential targets for surveillance and interventions. We compared several school-based influenza monitoring systems with clinic-based influenza-like illness (ILI surveillance, and assessed the variation in illness rates between and within schools. Methods During the initial wave of pandemic H1N1 (pdmH1N1 infections from June to Sept 2009 in Singapore, we collected data on nation-wide laboratory confirmed cases (Sch-LCC and daily temperature monitoring (Sch-DTM, and teacher-led febrile respiratory illness reporting in 6 sentinel schools (Sch-FRI. Comparisons were made against age-stratified clinic-based influenza-like illness (ILI data from 23 primary care clinics (GP-ILI and proportions of ILI testing positive for pdmH1N1 (Lab-ILI by computing the fraction of cumulative incidence occurring by epidemiological week 30 (when GP-ILI incidence peaked; and cumulative incidence rates between school-based indicators and sero-epidemiological pdmH1N1 incidence (estimated from changes in prevalence of A/California/7/2009 H1N1 hemagglutination inhibition titers ≥ 40 between pre-epidemic and post-epidemic sera. Variation in Sch-FRI rates in the 6 schools was also investigated through a Bayesian hierarchical model. Results By week 30, for primary and secondary school children respectively, 63% and 79% of incidence for Sch-LCC had occurred, compared with 50% and 52% for GP-ILI data, and 48% and 53% for Sch-FRI. There were 1,187 notified cases and 7,588 episodes in the Sch-LCC and Sch-DTM systems; given school enrollment of 485,723 children, this represented 0.24 cases and 1.6 episodes per 100 children respectively. Mean Sch-FRI rate was 28.8 per 100 children (95% CI: 27.7 to 29.9 in the 6 schools. We estimate from serology that 41.8% (95% CI: 30.2% to 55.9% of primary and 43.2% (95% CI: 28.2% to 60.8% of secondary school-aged children were infected. Sch-FRI rates were similar across

  16. Entfremdung als Strukturmoment von Unterricht? Eine Fallstudie zur Arbeit eines Schülers an der Tafel aus der Sicht der pädagogischen Unterrichtsforschung

    OpenAIRE

    Twardella, Johannes

    2010-01-01

    "In den 70er Jahren des 20. Jahrhunderts beobachtete Jules Henry im Rahmen seiner ethnographischen Schulforschungen die Arbeit eines Schülers an der Tafel und interpretierte sie aus einer sozialpsychologischen Perspektive heraus als einen Prozess, in dem ein Schüler lernt, was "Entfremdung" ist. Ausgehend von dieser Deutung wird in dem vorliegenden Aufsatz der Frage nachgegangen, ob der Begriff der Entfremdung auch heute noch für die Erforschung von Unterricht fruchtbar gemacht werden kann. D...

  17. Untersuchungen zum Einfluss der Betriebsbedingungen auf die Schädigung und Instandhaltung von Turboluftstrahltriebwerken

    OpenAIRE

    Müller, Matthias H.

    2013-01-01

    Langfristige Instandhaltungsverträge und der anhaltende Kostendruck haben die Notwendigkeit einer zuverlässigen Vorhersage und einer Reduzierung der Kosten für die Instandhaltung von Turboluftstrahltriebwerken zur Folge. Die Instandhaltungsbedürftigkeit und Zuverlässigkeit von Turboluftstrahltriebwerken wird wesentlich durch die betreibertypischen Betriebsbedingungen und die auftretenden Schädigungsmechanismen beeinflusst. Der Verlauf der Bauteilschädigung wird neben den Betriebsbedingungen d...

  18. Age dependencies in the modelling of radiation carcinogenesis

    International Nuclear Information System (INIS)

    Kellerer, A.M.; GSF, Neuherberg; Barclay, D.

    1992-01-01

    Models for the dose and age dependence of radiation induced cancer have been based primarily on the follow-up of the atomic bomb survivors. Two different concepts have been deduced for leukaemias and for other cancers. The excess leukaemias appear in a distinct temporal wave with a maximum 5 to 10 years after radiation exposure; the distribution is more narrow for younger ages, but there is little dependence of the total attributable risk on age at exposure. For other cancers the latent periods are longer and, according to the current interpretation, the excess rates are then proportional to the age specific spontaneous rates, so that most excess cases would arise at old age. The factors of proportionality, and thus the attributable risks, are assumed to be markedly higher for young ages at exposure. It is argued here, that there is no firm support for this interpretation. (author)

  19. Saussurea tridactyla Sch. Bip.-derived polysaccharides and flavones reduce oxidative damage in ultraviolet B-irradiated HaCaT cells via a p38MAPK-independent mechanism

    Directory of Open Access Journals (Sweden)

    Guo Y

    2016-01-01

    Full Text Available Yan Guo,1 Juan Sun,2 Juan Ye,1 Wenyu Ma,1 Hualing Yan,1 Gang Wang1 1Department of Dermatology and Venereology, Affiliated Hospital of Qinghai University, 2Department of Anatomy, Qinghai University Medical College, Xining, People’s Republic of China Objective: To investigate whether Saussurea tridactyla Sch. Bip.-derived polysaccharides and flavones exert apoptosis-inhibiting effects in ultraviolet B (UVB-irradiated HaCaT cells.Methods: We divided HaCaT cells into low radiation UVB and high radiation UVB groups. Low radiation UVB and high radiation UVB groups were further divided into a control group, UVB radiation group (UVB group, S. tridactyla Sch. Bip.-derived polysaccharides and flavones low-dose group, and S. tridactyla Sch. Bip.-derived polysaccharides and flavones high-dose group. Cell viability and morphology were assayed by MTT and trypan blue staining. Superoxide dismutase activity, glutathione content, malondialdehyde content, and catalase activity test kits were used to detect superoxide dismutase activity, glutathione content, malondialdehyde content, and catalase activity, respectively. Cell apoptosis, intracellular Ca2+ levels, and mitochondrial membrane potential (ΔΨ were detected by flow cytometry. Protein levels were analyzed by Western blotting and immunofluorescence.Results: S. tridactyla Sch. Bip.-derived polysaccharides and flavones were found to increase the absorbance of MTT, decrease cell death, alleviate the degree of cell edema, restore the cell morphology, reduce cell death fragments and chip phenomenon, increase superoxide dismutase activity, glutathione content, and catalase activity while decreasing the content of malondialdehyde, lowering the population of apoptotic cells, reducing the intracellular Ca2+ fluorescence, increasing the mitochondrial membrane potential (ΔΨ, increasing the expressions of p-38, p-53, Bcl-2, and decreasing the expressions of Bax and active-caspase-3.Conclusion: S. tridactyla Sch

  20. The Evolution of Juvenile Schönlein-Henoch Purpura

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    O.E. Chernyshova

    2016-10-01

    Full Text Available Background. Hemorrhagic vasculitis, or Schönlein-Henoch purpura (SHP, is the most common type of systemic vasculitis in childhood, and peculiarities of the further evolution of the pathological process in adult patients remain unexplored. Objective: to study the evolution of juvenile SHP, comparing the nature of lesions of the skin, joints, heart and kidneys in patients in childhood and adulthood. Material and methods. The study included 92 patients (61 men and 31 women with the average age of 27 years, and the average age of disease onset — 11 years. I degree of the activity of the pathological process is determined in 40 % of cases, II — in 35 %, III — in 25 %. Seropositivity by hyperimmunoglobulinemia A occurred in 27 % of cases, by the presence of rheumatoid factor — in 21 %. At the time of the survey, cutaneous syndrome was diagnosed in 55 % of patients, joint one — in 45 %, kidney one — in 71 %. Renal biopsy was performed in 15 cases. Results. The cutaneous, cutaneous-joint-abdominal and cutaneous-abdominal-renal forms of the disease, lesions of the skin, gastrointestinal tract, wrist, ankle and knee joints become rarer in the process of juvenile SHP evolution, but exceptionally renal variant of the pathological process, changes of skeletal muscles, liver, spleen and the heart are revealed more often, chronic kidney disease with the renal failure progression is developed in 12 % of patients (in 17 % of cases of nephropathy, sacroiliitis, spondylopathy, tendovaginitis, enthesopathies, epiphyseal osteoporosis and meniscitis of the knee joints are arisen, II, III, VI and IV morphological classes of Henoch glomerulonephritis are formed in a ratio of 8 : 4 : 2 : 1 with tubulointerstitial component in all cases, and lymphohistiocytic infiltration of the vascular wall is the unfavorable sign for the prognosis of the disease. Conclusions. In cases of transition of juvenile SHP into the chronic adult form, the disease often obtain

  1. AGE-DEPENDENT FEATURES OF EVOLVING HUMORAL IMMUNITY IN CHILDREN

    Directory of Open Access Journals (Sweden)

    A. P. Toptygina

    2012-01-01

    Full Text Available Abstract. Age dynamics of humoral immunity was studied in healthy children, i.e., 11 newborns, 33 infants of 4 to 8 months, 32 children of 1 to 2 years old,, 17 children of 4 to 5 years old, 25 children of 6 to 8 years old, 15 children of 9 to 11 years old, and 28 adolescents of 14 to 16 years old. Evaluation of membrane receptors on B cells was performed by means of three-colour fluorescent label and allowed of characterizing B1 subpopulations (CD19+CD5+CD27-, naпve B2 cells (CD19+CD5-CD27-, and B2 memory cells (CD19+CD5-CD27+. B1 cells have been shown to dominate in blood of newborns and younger children (up to 5 years old. By the contrary, B2 memory cells were nearly undetectable in newborns, and exceeded 20% in adolescents (by 15 years old. Meanwhile, it has been revealed that the amounts of IgG1 and IgG3 subclasses did progressively increase with age, whereas IgG2 remained decreased to 50% of adult values for a long time, and reached them by 11 years and later. We suggest that the age dynamics of IgG subclasses is connected with age-dependent changes in B cell subpopulations.

  2. Targeted deletion of Atg5 in chondrocytes promotes age-related osteoarthritis.

    Science.gov (United States)

    Bouderlique, Thibault; Vuppalapati, Karuna K; Newton, Phillip T; Li, Lei; Barenius, Björn; Chagin, Andrei S

    2016-03-01

    It has been suggested that the lysosomal recycling process called macro-autophagy plays a role in osteoarthritis development. We thus decided to genetically ablate the autophagy-indispensable Atg5 gene specifically in chondrocytes and analyse the development of osteoarthritis upon aging and in a post-traumatic model. Mice lacking the Atg5 gene in their chondrocytes (Atg5cKO) were generated by crossing Atg5-floxed mice with transgenic mice that expressed cre recombinase driven by the collagen type 2 promoter. Animals were analysed at the age of 2, 6 and 12 months for age-related osteoarthritis or underwent mini-open partial medial meniscectomy at 2 months of age and were analysed 1 or 2 months after surgery. We evaluated osteoarthritis using the Osteoarthritis Research Society International (OARSI) scoring on safranin-O-stained samples. Cell death was evaluated by terminal deoxy-nucleotidyl-transferase-mediated deoxy-UTP nick end labelling (TUNEL) and by immunostaining of cleaved caspases. We observed the development of osteoarthritis in Atg5cKO mice with aging including fibrillation and loss of proteoglycans, which was particularly severe in males. The ablation of Atg5 was associated with an increased cell death as assessed by TUNEL, cleaved caspase 3 and cleaved caspase 9. Surprisingly, no difference in the development of post-traumatic osteoarthritis was observed between Atg5cKO and control mice. Autophagy protects from age-related osteoarthritis by facilitating chondrocyte survival. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  3. NADPH oxidase/ROS-dependent PYK2 activation is involved in TNF-α-induced matrix metalloproteinase-9 expression in rat heart-derived H9c2 cells

    International Nuclear Information System (INIS)

    Yang, Chuen-Mao; Lee, I-Ta; Hsu, Ru-Chun; Chi, Pei-Ling; Hsiao, Li-Der

    2013-01-01

    TNF-α plays a mediator role in the pathogenesis of chronic heart failure contributing to cardiac remodeling and peripheral vascular disturbances. The implication of TNF-α in inflammatory responses has been shown to be mediated through up-regulation of matrix metalloproteinase-9 (MMP-9). However, the detailed mechanisms of TNF-α-induced MMP-9 expression in rat embryonic-heart derived H9c2 cells are largely not defined. We demonstrated that in H9c2 cells, TNF-α induced MMP-9 mRNA and protein expression associated with an increase in the secretion of pro-MMP-9. TNF-α-mediated responses were attenuated by pretreatment with the inhibitor of ROS (N-acetyl-L-cysteine, NAC), NADPH oxidase [apocynin (APO) or diphenyleneiodonium chloride (DPI)], MEK1/2 (U0126), p38 MAPK (SB202190), JNK1/2 (SP600125), NF-κB (Bay11-7082), or PYK2 (PF-431396) and transfection with siRNA of TNFR1, p47 phox , p42, p38, JNK1, p65, or PYK2. Moreover, TNF-α markedly induced NADPH oxidase-derived ROS generation in these cells. TNF-α-enhanced p42/p44 MAPK, p38 MAPK, JNK1/2, and NF-κB (p65) phosphorylation and in vivo binding of p65 to the MMP-9 promoter were inhibited by U0126, SB202190, SP600125, NAC, DPI, or APO. In addition, TNF-α-mediated PYK2 phosphorylation was inhibited by NAC, DPI, or APO. PYK2 inhibition could reduce TNF-α-stimulated MAPKs and NF-κB activation. Thus, in H9c2 cells, we are the first to show that TNF-α-induced MMP-9 expression is mediated through a TNFR1/NADPH oxidase/ROS/PYK2/MAPKs/NF-κB cascade. We demonstrated that NADPH oxidase-derived ROS generation is involved in TNF-α-induced PYK2 activation in these cells. Understanding the regulation of MMP-9 expression and NADPH oxidase activation by TNF-α on H9c2 cells may provide potential therapeutic targets of chronic heart failure. - Highlights: • TNF-α induces MMP-9 secretion and expression via a TNFR1-dependent pathway. • TNF-α induces ROS/PYK2-dependent MMP-9 expression in H9c2 cells. • TNF-α induces

  4. MiR-9-5p promotes MSC migration by activating β-catenin signaling pathway.

    Science.gov (United States)

    Li, Xianyang; He, Lihong; Yue, Qing; Lu, Junhou; Kang, Naixin; Xu, Xiaojing; Wang, Huihui; Zhang, Huanxiang

    2017-07-01

    Mesenchymal stem cells (MSCs) have the potential to treat various tissue damages, but the very limited number of cells that migrate to the damaged region strongly restricts their therapeutic applications. Full understanding of mechanisms regulating MSC migration will help to improve their migration ability and therapeutic effects. Increasing evidence shows that microRNAs play important roles in the regulation of MSC migration. In the present study, we reported that miR-9-5p was upregulated in hepatocyte growth factor -treated MSCs and in MSCs with high migration ability. Overexpression of miR-9-5p promoted MSC migration, whereas inhibition of endogenous miR-9-5p decreased MSC migration. To elucidate the underlying mechanism, we screened the target genes of miR-9-5p and report for the first time that CK1α and GSK3β, two inhibitors of β-catenin signaling pathway, were direct targets of miR-9-5p in MSCs and that overexpression of miR-9-5p upregulated β-catenin signaling pathway. In line with these data, inhibition of β-catenin signaling pathway by FH535 decreased the miR-9-5p-promoted migration of MSCs, while activation of β-catenin signaling pathway by LiCl rescued the impaired migration of MSCs triggered by miR-9-5p inhibitor. Furthermore, the formation and distribution of focal adhesions as well as the reorganization of F-actin were affected by the expression of miR-9-5p. Collectively, these results demonstrate that miR-9-5p promotes MSC migration by upregulating β-catenin signaling pathway, shedding light on the optimization of MSCs for cell replacement therapy through manipulating the expression level of miR-9-5p. Copyright © 2017 the American Physiological Society.

  5. Stability analysis for a general age-dependent vaccination model

    International Nuclear Information System (INIS)

    El Doma, M.

    1995-05-01

    An SIR epidemic model of a general age-dependent vaccination model is investigated when the fertility, mortality and removal rates depends on age. We give threshold criteria of the existence of equilibriums and perform stability analysis. Furthermore a critical vaccination coverage that is sufficient to eradicate the disease is determined. (author). 12 refs

  6. Age-dependent decay in the landscape

    International Nuclear Information System (INIS)

    Winitzki, Sergei

    2008-01-01

    The picture of the 'multiverse' arising in diverse cosmological scenarios involves transitions between metastable vacuum states. It was pointed out by Krauss and Dent that the transition rates decrease at very late times, leading to a dependence of the transition probability between vacua on the age of each vacuum region. I investigate the implications of this non-Markovian, age-dependent decay on the global structure of the spacetime in landscape scenarios. I show that the fractal dimension of the eternally inflating domain is precisely equal to 3, instead of being slightly below 3, which is the case in scenarios with purely Markovian, age-independent decay. I develop a complete description of a non-Markovian landscape in terms of a nonlocal master equation. Using this description I demonstrate by an explicit calculation that, under some technical assumptions about the landscape, the probabilistic predictions of our position in the landscape are essentially unchanged, regardless of the measure used to extract these predictions. I briefly discuss the physical plausibility of realizing non-Markovian vacuum decay in cosmology in view of the possible decoherence of the metastable quantum state.

  7. Age-dependent associations between androgenetic alopecia and prostate cancer risk.

    Science.gov (United States)

    Muller, David C; Giles, Graham G; Sinclair, Rod; Hopper, John L; English, Dallas R; Severi, Gianluca

    2013-02-01

    Both prostate cancer and androgenetic alopecia are strongly age-related conditions that are considered to be androgen dependent, but studies of the relationship between them have yielded inconsistent results. We aimed to assess whether androgenetic alopecia at ages 20 and 40 years are associated with risk of prostate cancer. At a follow-up of the Melbourne Collaborative Cohort Study, men were asked to assess their hair pattern at ages 20 and 40 years relative to eight categories in showcards. Cases were men notified to the Victorian Cancer Registry with prostate cancer diagnosed between cohort enrollment (1990-1994) and follow-up attendance (2003-2009). Flexible parametric survival models were used to estimate age-varying HRs and predicted cumulative probabilities of prostate cancer by androgenetic alopecia categories. Of 9,448 men that attended follow-up and provided data on androgenetic alopecia, we identified 476 prostate cancer cases during a median follow-up of 11 years four months. Cumulative probability of prostate cancer was greater at all ages up to 76 years, for men with vertex versus no androgenetic alopecia at age of 40 years. At age of 76 years, the estimated probabilities converged to 0.15. Vertex androgenetic alopecia at 40 years was also associated with younger age of diagnosis for prostate cancer cases. Vertex androgenetic alopecia at age of 40 years might be a marker of increased risk of early-onset prostate cancer. If confirmed, these results suggest that the apparently conflicting findings of previous studies might be explained by failure to adequately model the age-varying nature of the association between androgenetic alopecia and prostate cancer.

  8. Bistable Epigenetic States Explain Age-Dependent Decline in Mesenchymal Stem Cell Heterogeneity.

    Science.gov (United States)

    Hamidouche, Zahia; Rother, Karen; Przybilla, Jens; Krinner, Axel; Clay, Denis; Hopp, Lydia; Fabian, Claire; Stolzing, Alexandra; Binder, Hans; Charbord, Pierre; Galle, Joerg

    2017-03-01

    The molecular mechanisms by which heterogeneity, a major characteristic of stem cells, is achieved are yet unclear. We here study the expression of the membrane stem cell antigen-1 (Sca-1) in mouse bone marrow mesenchymal stem cell (MSC) clones. We show that subpopulations with varying Sca-1 expression profiles regenerate the Sca-1 profile of the mother population within a few days. However, after extensive replication in vitro, the expression profiles shift to lower values and the regeneration time increases. Study of the promoter of Ly6a unravels that the expression level of Sca-1 is related to the promoter occupancy by the activating histone mark H3K4me3. We demonstrate that these findings can be consistently explained by a computational model that considers positive feedback between promoter H3K4me3 modification and gene transcription. This feedback implicates bistable epigenetic states which the cells occupy with an age-dependent frequency due to persistent histone (de-)modification. Our results provide evidence that MSC heterogeneity, and presumably that of other stem cells, is associated with bistable epigenetic states and suggest that MSCs are subject to permanent state fluctuations. Stem Cells 2017;35:694-704. © The Authors Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  9. Age at onset typology in opioid dependent men: an exploratory study.

    Science.gov (United States)

    De, Biswajit; Mattoo, Surendra K; Basu, Debasish

    2002-04-01

    This study attempted to apply age at onset typology in ICD-10 diagnosed opioid dependence. The sample comprised 80 men seeking treatment at an addiction clinic. The measures included socio-demographic and clinical profile, Severity of Opioid Dependence Questionnaire, Modified Sensation Seeking Scale, Multiphasic Personality Questionnaire (MPQ) and Family History Assessment Module. A cut-off age of 20/21 years for an early-onset late-onset typology of opioid dependence was obtained using two methods - the modal age at onset method and one-third sample by age at onset method. The early onset group showed significant differences in terms of it being more often younger, urban, unmarried, wage earning or students, using oral opioids (not heroin or injectables), showing higher lifetime use and dependence of sedatives, earlier onset of use and dependence of sedatives and tobacco, and higher global psychopathology in terms of MPQ. The early onset group also showed statistically insignificant trends for lesser use and dependence of alcohol, higher severity of opioid dependence, more legal and less social complications, higher sensation seeking (except boredom susceptibility), and more frequent substance dependence in first degree relatives. The age at onset typology in opioid dependence appears to be feasible and having some similarities to similar typology in alcoholism.

  10. Age- and brain region-dependent α-synuclein oligomerization is attributed to alterations in intrinsic enzymes regulating α-synuclein phosphorylation in aging monkey brains.

    Science.gov (United States)

    Chen, Min; Yang, Weiwei; Li, Xin; Li, Xuran; Wang, Peng; Yue, Feng; Yang, Hui; Chan, Piu; Yu, Shun

    2016-02-23

    We previously reported that the levels of α-syn oligomers, which play pivotal pathogenic roles in age-related Parkinson's disease (PD) and dementia with Lewy bodies, increase heterogeneously in the aging brain. Here, we show that exogenous α-syn incubated with brain extracts from older cynomolgus monkeys and in Lewy body pathology (LBP)-susceptible brain regions (striatum and hippocampus) forms higher amounts of phosphorylated and oligomeric α-syn than that in extracts from younger monkeys and LBP-insusceptible brain regions (cerebellum and occipital cortex). The increased α-syn phosphorylation and oligomerization in the brain extracts from older monkeys and in LBP-susceptible brain regions were associated with higher levels of polo-like kinase 2 (PLK2), an enzyme promoting α-syn phosphorylation, and lower activity of protein phosphatase 2A (PP2A), an enzyme inhibiting α-syn phosphorylation, in these brain extracts. Further, the extent of the age- and brain-dependent increase in α-syn phosphorylation and oligomerization was reduced by inhibition of PLK2 and activation of PP2A. Inversely, phosphorylated α-syn oligomers reduced the activity of PP2A and showed potent cytotoxicity. In addition, the activity of GCase and the levels of ceramide, a product of GCase shown to activate PP2A, were lower in brain extracts from older monkeys and in LBP-susceptible brain regions. Our results suggest a role for altered intrinsic metabolic enzymes in age- and brain region-dependent α-syn oligomerization in aging brains.

  11. Fatigue Properties of Aged Mod. 9Cr-1Mo

    International Nuclear Information System (INIS)

    Kim, Dae Whan; Kim, Sung Ho; Lee, Chan Bock

    2007-01-01

    Ferritic/Martensitic steel has a good mechanical properties and a lower thermal expansion coefficient than austenitic stainless steel. Mechanical property of Mod. 9Cr-1Mo steel is less than austenitic stainless steel at high temperature. High temperature mechanical properties are affected by precipitation for Mod. 9Cr-1Mo. FMS steel is used for long time at high temperature and the effect of aging on mechanical properties is very important. In this study, low cycle fatigue properties with aging were investigated

  12. Age-dependent metabolic model of radionuclides in Human body

    International Nuclear Information System (INIS)

    Ye Changqing

    1986-01-01

    Age-dependent metabolic model of radionuclides in human body was introduced briefly. These data are necessary in setting up the secondary dose limit of internal exposure of the general public. For the gastro-intestinal tract model, it was shown that the dose of various sections of GI tract caused by unsoluble radioactive materials were influenced by the mass of section and mean residence time, both of which are age-dependent, but the absorption fraction f 1 through gastro-intestinal tract should be corrected only for the infant less than 1 year of age. For the lung model, it was indicated that the fraction of deposition or clearance of particles in the different compartments of lung were related to age. The doses of tracheobronchial and pulmonary compartment of adult for 222 Rn or 220 Rn with their decay products were one third of that of 6-years old child who received the maximum dose in comparison with other ages. The age-dependent metabolic models in organ and/or body of Tritium, Iodine-131, Caesium-137, radioactive Strontium, Radium and Plutonium were reported. A generalized approach for estimating the effect of age on deposition fractions and retention half-time were presented. Calculated results indicated that younger ages were characterized by increased deposition fraction and decreased half-time for retention. Representative examples were provided for 21 elements of current interest in health physics

  13. Vasotrophic Regulation of Age-Dependent Hypoxic Cerebrovascular Remodeling

    Science.gov (United States)

    Silpanisong, Jinjutha; Pearce, William J.

    2015-01-01

    Hypoxia can induce functional and structural vascular remodeling by changing the expression of trophic factors to promote homeostasis. While most experimental approaches have been focused on functional remodeling, structural remodeling can reflect changes in the abundance and organization of vascular proteins that determine functional remodeling. Better understanding of age-dependent hypoxic macrovascular remodeling processes of the cerebral vasculature and its clinical implications require knowledge of the vasotrophic factors that influence arterial structure and function. Hypoxia can affect the expression of transcription factors, classical receptor tyrosine kinase factors, non-classical G-protein coupled factors, catecholamines, and purines. Hypoxia’s remodeling effects can be mediated by Hypoxia Inducible Factor (HIF) upregulation in most vascular beds, but alterations in the expression of growth factors can also be independent of HIF. PPARγ is another transcription factor involved in hypoxic remodeling. Expression of classical receptor tyrosine kinase ligands, including vascular endothelial growth factor, platelet derived growth factor, fibroblast growth factor and angiopoietins, can be altered by hypoxia which can act simultaneously to affect remodeling. Tyrosine kinase-independent factors, such as transforming growth factor, nitric oxide, endothelin, angiotensin II, catecholamines, and purines also participate in the remodeling process. This adaptation to hypoxic stress can fundamentally change with age, resulting in different responses between fetuses and adults. Overall, these mechanisms integrate to assure that blood flow and metabolic demand are closely matched in all vascular beds and emphasize the view that the vascular wall is a highly dynamic and heterogeneous tissue with multiple cell types undergoing regular phenotypic transformation. PMID:24063376

  14. Presence of Insulin-Like Growth Factor Binding Proteins Correlates With Tumor-Promoting Effects of Matrix Metalloproteinase 9 in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Jae-Hyun Park

    2015-05-01

    Full Text Available The stroma of breast cancer can promote the disease’s progression, but whether its composition and functions are shared among different subtypes is poorly explored. We compared stromal components of a luminal [mouse mammary tumor virus (MMTV–Neu] and a triple-negative/basal-like [C3(1–Simian virus 40 large T antigen (Tag] genetically engineered breast cancer mouse model. The types of cytokines and their expression levels were very different in the two models, as was the extent of innate immune cell infiltration; however, both models showed infiltration of innate immune cells that expressed matrix metalloproteinase 9 (MMP9, an extracellular protease linked to the progression of many types of cancer. By intercrossing with Mmp9 null mice, we found that the absence of MMP9 delayed tumor onset in the C3(1-Tag model but had no effect on tumor onset in the MMTV-Neu model. We discovered that protein levels of insulin-like growth factor binding protein-1 (IGFBP-1, an MMP9 substrate, were increased in C3(1-Tag;Mmp9−/− compared to C3(1-Tag;Mmp9+/+ tumors. In contrast, IGFBP-1 protein expression was low in MMTV-Neu tumors regardless of Mmp9 status. IGFBP-1 binds and antagonizes IGFs, preventing them from activating their receptors to promote cell proliferation and survival. Tumors from C3(1-Tag;Mmp9−/− mice had reduced IGF-1 receptor phosphorylation, consistent with slower tumor onset. Finally, gene expression analysis of human breast tumors showed that high expression of IGFBP mRNA was strongly correlated with good prognosis but not when MMP9 mRNA was also highly expressed. In conclusion, MMP9 has different effects on breast cancer progression depending on whether IGFBPs are expressed.

  15. Healthy and Active Ageing: Social Capital in Health Promotion

    Science.gov (United States)

    Koutsogeorgou, Eleni; Davies, John Kenneth; Aranda, Kay; Zissi, Anastasia; Chatzikou, Maria; Cerniauskaite, Milda; Quintas, Rui; Raggi, Alberto; Leonardi, Matilde

    2014-01-01

    Objectives: This paper examines the context of health promotion actions that are focused on/contributing to strengthening social capital by increasing community participation, reciprocal trust and support as the means to achieve better health and more active ageing. Method: The methodology employed was a literature review/research synthesis, and a…

  16. In vivo efficacy of SM-8668 (Sch 39304), a new oral triazole antifungal agent.

    Science.gov (United States)

    Tanio, T; Ichise, K; Nakajima, T; Okuda, T

    1990-06-01

    SM-8668 (Sch 39304) is a new oral antifungal agent which we evaluated in comparison with fluconazole in various fungal infection models. The prophylactic effect of SM-8668 was excellent against systemic candidiasis, aspergillosis, and cryptococcosis in mice. The 50% effective dose for SM-8668 was assessed at 10 days after infection and was 0.18, 3.7, and 5.9 mg/kg (body weight), respectively, for the above-mentioned fungal diseases. Fluconazole was about four times less effective than SM-8668 against systemic candidiasis and was only slightly effective at doses of 80 and 25 mg/kg against systemic aspergilosis and cryptococcosis, respectively. SM-8668 was also about four to eight times more active than fluconazole against vaginal candidiasis in rats and against dermatophytic infection in guinea pigs. In addition, topical SM-8668 was as effective as topical miconazole or tioconazole against skin mycosis in guinea pigs. After oral administration, SM-8668 showed a maximum concentration in serum similar to that of fluconazole in both mice and rats, but the elimination half-life and area under the serum concentration-time curve for SM-8668 were twice those for fluconazole.

  17. Heterologous and endogenous U6 snRNA promoters enable CRISPR/Cas9 mediated genome editing in Aspergillus niger.

    Science.gov (United States)

    Zheng, Xiaomei; Zheng, Ping; Sun, Jibin; Kun, Zhang; Ma, Yanhe

    2018-01-01

    U6 promoters have been used for single guide RNA (sgRNA) transcription in the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas9) genome editing system. However, no available U6 promoters have been identified in Aspergillus niger, which is an important industrial platform for organic acid and protein production. Two CRISPR/Cas9 systems established in A. niger have recourse to the RNA polymerase II promoter or in vitro transcription for sgRNA synthesis, but these approaches generally increase cloning efforts and genetic manipulation. The validation of functional RNA polymerase II promoters is therefore an urgent need for A. niger . Here, we developed a novel CRISPR/Cas9 system in A. niger for sgRNA expression, based on one endogenous U6 promoter and two heterologous U6 promoters. The three tested U6 promoters enabled sgRNA transcription and the disruption of the polyketide synthase albA gene in A. niger . Furthermore, this system enabled highly efficient gene insertion at the targeted genome loci in A. niger using donor DNAs with homologous arms as short as 40-bp. This study demonstrated that both heterologous and endogenous U6 promoters were functional for sgRNA expression in A. niger . Based on this result, a novel and simple CRISPR/Cas9 toolbox was established in A. niger, that will benefit future gene functional analysis and genome editing.

  18. TREM2 Overexpression has No Improvement on Neuropathology and Cognitive Impairment in Aging APPswe/PS1dE9 Mice.

    Science.gov (United States)

    Jiang, Teng; Wan, Yu; Zhang, Ying-Dong; Zhou, Jun-Shan; Gao, Qing; Zhu, Xi-Chen; Shi, Jian-Quan; Lu, Huan; Tan, Lan; Yu, Jin-Tai

    2017-03-01

    Previously, we showed that overexpression of triggering receptor expressed on myeloid cells 2 (TREM2), a microglia-specific immune receptor, in the brain of a middle-aged (7 months old) APPswe/PS1dE9 mice could ameliorate Alzheimer's disease (AD)-related neuropathology by enhancement of microglial amyloid-β (Aβ) phagocytosis. Since AD is an age-related neurodegenerative disorder, it is critical to assess the efficacy of TREM2 overexpression in aging animals with an advanced disease stage. In vivo, we employed a lentiviral strategy to overexpress TREM2 in the brain of aging (18 months old) APPswe/PS1dE9 mice, and observed its efficacy on AD-related neuropathology and cognitive functions. Afterwards, we directly isolated microglia from middle-aged and aging APPswe/PS1dE9 mice and determined effects of TREM2 overexpression on microglial Aβ phagocytosis and Aβ-binding receptors expression in vitro. In aging APPswe/PS1dE9 mice, TREM2 overexpression has no beneficial effect on AD-related neuropathology and spatial cognitive functions. Of note, in vitro experiments showed a significant reduction of Aβ phagocytosis in microglia from aging APPswe/PS1dE9 mice, possibly attributing to the declined expression of Aβ-binding receptors. Meanwhile, this phagocytic deficit in microglia from aging APPswe/PS1dE9 mice cannot be rescued by TREM2 overexpression. Taken together, our study shows that TREM2 overexpression fails to provide neuroprotection in aging APPswe/PS1dE9 mice, possibly attributing to deficits in microglial Aβ phagocytosis at the late-stage of disease progression. These findings indicate that TREM2-mediated protection in AD is at least partially dependent on the reservation of microglial phagocytic functions, emphasizing the importance of early therapeutic interventions for this devastating disease.

  19. The DNA-mimic antirestriction proteins ArdA ColIB-P9, Arn T4, and Ocr T7 as activators of H-NS-dependent gene transcription.

    Science.gov (United States)

    Melkina, Olga E; Goryanin, Ignatiy I; Zavilgelsky, Gennadii B

    2016-11-01

    The antirestriction proteins ArdA ColIb-P9, Arn T4 and Ocr T7 specifically inhibit type I and type IV restriction enzymes and belong to the family of DNA-mimic proteins because their three-dimensional structure is similar to the double-helical B-form DNA. It is proposed that the DNA-mimic proteins are able to bind nucleoid protein H-NS and alleviate H-NS-silencing of the transcription of bacterial genes. Escherichia coli lux biosensors were constructed by inserting H-NS-dependent promoters into a vector, thereby placing each fragment upstream of the promoterless Photorhabdus luminescens luxCDABE operon. It was demonstrated that the DNA-mimic proteins ArdA, Arn and Ocr activate the transcription of H-NS-dependent promoters of the lux operon of marine luminescent bacteria (mesophilic Aliivibrio fischeri and psychrophilic Aliivibrio logei), and the dps gene from E. coli. It was also demonstrated that the ArdA antirestriction protein, the genes of which are located on transmissive plasmids ColIb-P9, R64, PK101, decreases levels of H-NS silencing of the PluxC promoter during conjugation in the recipient bacteria. Copyright © 2016 Elsevier GmbH. All rights reserved.

  20. ROCK inhibition stimulates SOX9/Smad3-dependent COL2A1 expression in inner meniscus cells.

    Science.gov (United States)

    Furumatsu, Takayuki; Maehara, Ami; Ozaki, Toshifumi

    2016-07-01

    Proper functioning of the meniscus depends on the composition and organization of its fibrocartilaginous extracellular matrix. We previously demonstrated that the avascular inner meniscus has a more chondrocytic phenotype compared with the outer meniscus. Inhibition of the Rho family GTPase ROCK, the major regulator of the actin cytoskeleton, stimulates the chondrogenic transcription factor Sry-type HMG box (SOX) 9-dependent α1(II) collagen (COL2A1) expression in inner meniscus cells. However, the crosstalk between ROCK inhibition, SOX9, and other transcription modulators on COL2A1 upregulation remains unclear in meniscus cells. The aim of this study was to investigate the role of SOX9-related transcriptional complex on COL2A1 expression under the inhibition of ROCK in human meniscus cells. Human inner and outer meniscus cells were prepared from macroscopically intact lateral menisci. Cells were cultured in the presence or absence of ROCK inhibitor (ROCKi, Y27632). Gene expression, collagen synthesis, and nuclear translocation of SOX9 and Smad2/3 were analyzed. Treatment of ROCKi increased the ratio of type I/II collagen double positive cells derived from the inner meniscus. In real-time PCR analyses, expression of SOX9 and COL2A1 genes was stimulated by ROCKi treatment in inner meniscus cells. ROCKi treatment also induced nuclear translocation of SOX9 and phosphorylated Smad2/3 in immunohistological analyses. Complex formation between SOX9 and Smad3 was increased by ROCKi treatment in inner meniscus cells. Chromatin immunoprecipitation analyses revealed that association between SOX9/Smad3 transcriptional complex with the COL2A1 enhancer region was increased by ROCKi treatment. This study demonstrated that ROCK inhibition stimulated SOX9/Smad3-dependent COL2A1 expression through the immediate nuclear translocation of Smad3 in inner meniscus cells. Our results suggest that ROCK inhibition can stimulates type II collagen synthesis through the cooperative activation

  1. Estimating Age-Dependent Extinction: Contrasting Evidence from Fossils and Phylogenies.

    Science.gov (United States)

    Hagen, Oskar; Andermann, Tobias; Quental, Tiago B; Antonelli, Alexandre; Silvestro, Daniele

    2018-05-01

    The estimation of diversification rates is one of the most vividly debated topics in modern systematics, with considerable controversy surrounding the power of phylogenetic and fossil-based approaches in estimating extinction. Van Valen's seminal work from 1973 proposed the "Law of constant extinction," which states that the probability of extinction of taxa is not dependent on their age. This assumption of age-independent extinction has prevailed for decades with its assessment based on survivorship curves, which, however, do not directly account for the incompleteness of the fossil record, and have rarely been applied at the species level. Here, we present a Bayesian framework to estimate extinction rates from the fossil record accounting for age-dependent extinction (ADE). Our approach, unlike previous implementations, explicitly models unobserved species and accounts for the effects of fossil preservation on the observed longevity of sampled lineages. We assess the performance and robustness of our method through extensive simulations and apply it to a fossil data set of terrestrial Carnivora spanning the past 40 myr. We find strong evidence of ADE, as we detect the extinction rate to be highest in young species and declining with increasing species age. For comparison, we apply a recently developed analogous ADE model to a dated phylogeny of extant Carnivora. Although the phylogeny-based analysis also infers ADE, it indicates that the extinction rate, instead, increases with increasing taxon age. The estimated mean species longevity also differs substantially, with the fossil-based analyses estimating 2.0 myr, in contrast to 9.8 myr derived from the phylogeny-based inference. Scrutinizing these discrepancies, we find that both fossil and phylogeny-based ADE models are prone to high error rates when speciation and extinction rates increase or decrease through time. However, analyses of simulated and empirical data show that fossil-based inferences are more

  2. Histone Deacetylase 7 Promotes Toll-like Receptor 4-dependent Proinflammatory Gene Expression in Macrophages*

    Science.gov (United States)

    Shakespear, Melanie R.; Hohenhaus, Daniel M.; Kelly, Greg M.; Kamal, Nabilah A.; Gupta, Praveer; Labzin, Larisa I.; Schroder, Kate; Garceau, Valerie; Barbero, Sheila; Iyer, Abishek; Hume, David A.; Reid, Robert C.; Irvine, Katharine M.; Fairlie, David P.; Sweet, Matthew J.

    2013-01-01

    Broad-spectrum inhibitors of histone deacetylases (HDACs) constrain Toll-like receptor (TLR)-inducible production of key proinflammatory mediators. Here we investigated HDAC-dependent inflammatory responses in mouse macrophages. Of the classical Hdacs, Hdac7 was expressed at elevated levels in inflammatory macrophages (thioglycollate-elicited peritoneal macrophages) as compared with bone marrow-derived macrophages and the RAW264 cell line. Overexpression of a specific, alternatively spliced isoform of Hdac7 lacking the N-terminal 22 amino acids (Hdac7-u), but not the Refseq Hdac7 (Hdac7-s), promoted LPS-inducible expression of Hdac-dependent genes (Edn1, Il-12p40, and Il-6) in RAW264 cells. A novel class IIa-selective HDAC inhibitor reduced recombinant human HDAC7 enzyme activity as well as TLR-induced production of inflammatory mediators in thioglycollate-elicited peritoneal macrophages. Both LPS and Hdac7-u up-regulated the activity of the Edn1 promoter in an HDAC-dependent fashion in RAW264 cells. A hypoxia-inducible factor (HIF) 1 binding site in this promoter was required for HDAC-dependent TLR-inducible promoter activity and for Hdac7- and HIF-1α-mediated trans-activation. Coimmunoprecipitation assays showed that both Hdac7-u and Hdac7-s interacted with HIF-1α, whereas only Hdac7-s interacted with the transcriptional repressor CtBP1. Thus, Hdac7-u positively regulates HIF-1α-dependent TLR signaling in macrophages, whereas an interaction with CtBP1 likely prevents Hdac7-s from exerting this effect. Hdac7 may represent a potential inflammatory disease target. PMID:23853092

  3. Histone deacetylase 7 promotes Toll-like receptor 4-dependent proinflammatory gene expression in macrophages.

    Science.gov (United States)

    Shakespear, Melanie R; Hohenhaus, Daniel M; Kelly, Greg M; Kamal, Nabilah A; Gupta, Praveer; Labzin, Larisa I; Schroder, Kate; Garceau, Valerie; Barbero, Sheila; Iyer, Abishek; Hume, David A; Reid, Robert C; Irvine, Katharine M; Fairlie, David P; Sweet, Matthew J

    2013-08-30

    Broad-spectrum inhibitors of histone deacetylases (HDACs) constrain Toll-like receptor (TLR)-inducible production of key proinflammatory mediators. Here we investigated HDAC-dependent inflammatory responses in mouse macrophages. Of the classical Hdacs, Hdac7 was expressed at elevated levels in inflammatory macrophages (thioglycollate-elicited peritoneal macrophages) as compared with bone marrow-derived macrophages and the RAW264 cell line. Overexpression of a specific, alternatively spliced isoform of Hdac7 lacking the N-terminal 22 amino acids (Hdac7-u), but not the Refseq Hdac7 (Hdac7-s), promoted LPS-inducible expression of Hdac-dependent genes (Edn1, Il-12p40, and Il-6) in RAW264 cells. A novel class IIa-selective HDAC inhibitor reduced recombinant human HDAC7 enzyme activity as well as TLR-induced production of inflammatory mediators in thioglycollate-elicited peritoneal macrophages. Both LPS and Hdac7-u up-regulated the activity of the Edn1 promoter in an HDAC-dependent fashion in RAW264 cells. A hypoxia-inducible factor (HIF) 1 binding site in this promoter was required for HDAC-dependent TLR-inducible promoter activity and for Hdac7- and HIF-1α-mediated trans-activation. Coimmunoprecipitation assays showed that both Hdac7-u and Hdac7-s interacted with HIF-1α, whereas only Hdac7-s interacted with the transcriptional repressor CtBP1. Thus, Hdac7-u positively regulates HIF-1α-dependent TLR signaling in macrophages, whereas an interaction with CtBP1 likely prevents Hdac7-s from exerting this effect. Hdac7 may represent a potential inflammatory disease target.

  4. Henoch-Schönlein purpura in adults: a case series from a multidisciplinary study group Púrpura de Henoch-Schönlein em adultos: uma série de casos de um grupo de estudo multidisciplinar

    Directory of Open Access Journals (Sweden)

    Boris A. Cruz

    2006-12-01

    Full Text Available BACKGROUND: Henoch-Schönlein purpura (HSP is a systemic vasculitis involving small vessels with the deposition of immune complexes containing IgA. It has been extensively studied in children, but in adults, its natural history is much less known. OBJECTIVES: to report a series of patients with HSP presenting in their adulthood. PATIENTS AND METHODS: the Minas Gerais Vasculitis Study Group´s Members (MGVSG were invited to report patients with HSP who appeared in their adulthood. A standardized retrospective chart review was done. RESULTS: eleven patients, two male and nine female, age 39.4 +/- 20.1 yearsold were studied. Nine patients presented purpura, seven presented arthritis, four patients had gastrointestinal involvement and ten patients (91% presented glomerulonephritis (GN. Eight patients were subjected to renal biopsies. Six of them presented endocapillary proliferative GN and only two of them had minimal mesangial proliferation. In the other three patients, HSP was confirmed by skin biopsies. All patients received steroids, in five of them steroids were combined with other immunosuppressive agents. After a follow-up of 39.0 +/- 64.6 months, four patients (36% presented impairment of renal function, but only one (9% developed end stage renal disease and was successfully appeared to renal transplantation. At the end of follow-up, seven patients (64% are in complete remission and four in partial remission. CONCLUSION: in adulthood, HSP represents a distinct clinical syndrome with a higher frequency of renal involvement and more severe systemic vasculitis. Nevertheless, the final outcome in this series was as good as reported in children, maybe due to aggressive immunosuppressive therapy.INTRODUÇÃO: púrpura de Henoch-Schönlein (PHS é uma vasculite sistêmica que acomete vasos de pequeno calibre com depósitos de imunocomplexos contendo IgA. Esta vasculite já foi extensamente estudada em crianças, mas sua história natural em adultos

  5. Herpesviral ICP0 Protein Promotes Two Waves of Heterochromatin Removal on an Early Viral Promoter during Lytic Infection

    Directory of Open Access Journals (Sweden)

    Jennifer S. Lee

    2016-01-01

    Full Text Available Herpesviruses must contend with host cell epigenetic silencing responses acting on their genomes upon entry into the host cell nucleus. In this study, we confirmed that unchromatinized herpes simplex virus 1 (HSV-1 genomes enter primary human foreskin fibroblasts and are rapidly subjected to assembly of nucleosomes and association with repressive heterochromatin modifications such as histone 3 (H3 lysine 9-trimethylation (H3K9me3 and lysine 27-trimethylation (H3K27me3 during the first 1 to 2 h postinfection. Kinetic analysis of the modulation of nucleosomes and heterochromatin modifications over the course of lytic infection demonstrates a progressive removal that coincided with initiation of viral gene expression. We obtained evidence for three phases of heterochromatin removal from an early gene promoter: an initial removal of histones and heterochromatin not dependent on ICP0, a second ICP0-dependent round of removal of H3K9me3 that is independent of viral DNA synthesis, and a third phase of H3K27me3 removal that is dependent on ICP0 and viral DNA synthesis. The presence of ICP0 in transfected cells is also sufficient to promote removal of histones and H3K9me3 modifications of cotransfected genes. Overall, these results show that ICP0 promotes histone removal, a reduction of H3K9me3 modifications, and a later indirect reduction of H3K27me3 modifications following viral early gene expression and DNA synthesis. Therefore, HSV ICP0 promotes the reversal of host epigenetic silencing mechanisms by several mechanisms.

  6. Teachers' Promotion or Inhibition of Children's Aggression Depends on Peer-Group Characteristics.

    Science.gov (United States)

    Peets, Kätlin; Kikas, Eve

    2017-01-01

    Researchers have increasingly started to pay attention to how contextual factors, such as the classroom peer context and the quality of student-teacher interactions, influence children's aggressive behavior. This longitudinal study was designed to examine the degree to which benefits and costs of different teaching practices (child-centered and child-dominated) would be dependent on the initial peer-group composition (aggregate levels of aggression and victimization at the beginning of first grade). Teachers provided ratings of aggression and victimization (N = 523 first-grade students; M age at the beginning of first grade = 7.49 years, SD = 0.52). Information about different teaching practices was obtained via observations. Our results show that whereas child-centered practices are beneficial in high-victimization classrooms, child-dominated practices inhibit the development of aggression in low-victimization classroom contexts. Our findings highlight the importance of moving beyond main-effect models to studying how different contextual influences interact to promote, or inhibit, the development of aggression.

  7. The acoustical significance of age-dependent ear elongation

    DEFF Research Database (Denmark)

    Christensen, Flemming

    2015-01-01

    , corresponding to what is reported in the literature. For female ears, virtually no acoustical effect was found. For male ears directional dependent effects in the range up to 5 dB on average was found for certain directions and frequencies. Implications on age dependent hearing loss (presbycusis...

  8. Thyrotropin levels are associated with chronic kidney disease among healthy subjects in cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

    Science.gov (United States)

    Peixoto de Miranda, Érique José F; Bittencourt, Márcio Sommer; Goulart, Alessandra C; Santos, Itamar S; de Oliveira Titan, Silvia Maria; Ladeira, Roberto Marini; Barreto, Sandhi Maria; Lotufo, Paulo A; Benseñor, Isabela Judith Martins

    2017-12-01

    Few studies have evaluated a possible relationship between thyrotropin levels and glomerular filtration rate (GFR) and albumin/creatinine ratio in euthyroid subjects. We aimed to analyze this association using baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Cross-sectionally, we included subjects with normal thyroid function and with subclinical hypothyroidism (SCH). We excluded individuals using medications that affect thyroid function. Linear and logistic regression models evaluated GFR estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) and albuminuria/creatinine ratio as dependent variables and thyrotropin quartiles in individuals with euthyroidism and SCH as independent variables, adjusted for demographical characteristics and diseases related to CKD. We included 13,193 subjects with a median age of 51 years [interquartile range, (IQR): 45-58], 6840 (51.8%) women, 12,416 (94.1%) euthyroid, and 777 (5.9%) with SCH. SCH subjects were characterized by higher age, triglycerides, frequency of white race, cardiovascular disease, CKD, and former smokers. In adjusted models, log-transformed TSH in euthyroid subjects was inversely and strongly associated with CKD (β = -2.181, 95% CI -2.714 to -1.648), P < 0.0001 for glomerular filtration rate and 4.528 (1.190-7.865) for albuminuria/creatinine ratio. Multivariate logistic models for euthyroid subjects showed an OR of 1.45 (95% CI 1.15-1.83) for GFR and of 1.95 (95% CI 1.08-3.54) for albuminuria/creatinine ratio in the fourth quartile of TSH using the first as the reference. Thyrotropin levels are independently associated with CKD in euthyroid subjects.

  9. Plaque deposition dependent decrease in 5-HT2A serotonin receptor in AbetaPPswe/PS1dE9 amyloid overexpressing mice

    DEFF Research Database (Denmark)

    Holm, Peter; Ettrup, Anders; Klein, Anders B

    2010-01-01

    -HT2A receptor regulation in double transgenic AbetaPPswe/PS1dE9 mice which display excess production of Abeta and age-dependent increase in amyloid plaques. Three different age-groups, 4-month-old, 8- month-old, and 11-month-old were included in the study. [3H]-MDL100907, [3H]-escitalopram, and [11C...

  10. Evocatin of the Spirit: A-capella-Werke von Gorecki, Pärt, Martin, Barber und Schönberg / Gerhard Pätzig

    Index Scriptorium Estoniae

    Pätzig, Gerhard

    1995-01-01

    Uuest heliplaadist "Evocatin of the Spirit: A-capella-Werke von Gorecki, Pärt, Martin, Barber und Schönberg. Robert Shaw Festival Singers. Robert Shaw (AD: 1994). Telarc/in-akustik CD 80406 (WD: 72'15")

  11. Mar à Vista: Explorando as Estratégias da Familia Schürmann a Bordo de um Veleiro [doi: 10.5329/RECADM.20080702007

    Directory of Open Access Journals (Sweden)

    Antonio Eduardo Husadel

    2008-11-01

    Full Text Available Normal 0 21 false false false PT-BR X-NONE X-NONE MicrosoftInternetExplorer4 RESUMO Novos contornos começaram a ser delineados no campo da estratégia, nas últimas décadas, resultando no surgimento de estudos centrados no entendimento do processo de formação de estratégia à medida em que o mesmo se desenvolve. Mintzberg, Ahlstrand e Lampel (1999 propuseram a analogia da estratégia como um elefante de dez partes, sugerindo que o campo da estratégia é visto por suas partes, o que impossibilita sua reconstituição, pois para entender o todo, é preciso conhecer cada uma das partes que o compõem. Na mesma direção, Vasconcelos (2001 identifica, a partir desses autores, três dimensões da estratégia. Da experiência acumulada em uma circunavegação pelo planeta, o que era, inicialmente, a realização de um sonho, a Familia Schürmann inovou e criou uma empresa com características inconfundíveis, conquistando espaço em um mercado já bastante explorado. Esta pesquisa ancora-se na abordagem interpretativa e tem como objetivo explorar o processo de formação da estratégia, utilizando a experiência da família Schürmann desde sua trajetória na volta ao mundo a bordo de um veleiro. Entrevistas e documentos institucionais foram utilizados como fontes da pesquisa. Como resultado, é apresentado o processo de formação da estratégia da Família Schürmann, evidenciando aspectos de diferentes escolas de pensamento estratégico.   Palavras-Chave Estratégia. Inovação. Aprendizagem. Cultura. Schurmann.     ABSTRACT New contours began to be outlined in the strategy field, in recent decades, resulting in the emergence of studies focused on understanding the process strategy formation on the extent to which it develops. Mintzberg, Ahlstrand & Lampel (1999 proposed the analogy of the elephant as a strategy of ten parties, suggesting that the field of strategy is seen by its parts, which makes their recovery, because to understand the

  12. Assessing age-dependent susceptibility to measles in Japan.

    Science.gov (United States)

    Kinoshita, Ryo; Nishiura, Hiroshi

    2017-06-05

    Routine vaccination against measles in Japan started in 1978. Whereas measles elimination was verified in 2015, multiple chains of measles transmission were observed in 2016. We aimed to reconstruct the age-dependent susceptibility to measles in Japan so that future vaccination strategies can be elucidated. An epidemiological model was used to quantify the age-dependent immune fraction using datasets of vaccination coverage and seroepidemiological survey. The second dose was interpreted in two different scenarios, i.e., booster and random shots. The effective reproduction number, the average number of secondary cases generated by a single infected individual, and the age at infection were explored using the age-dependent transmission model and the next generation matrix. While the herd immunity threshold of measles likely ranges from 90% to 95%, assuming that the basic reproductive number ranges from 10 to 20, the estimated immune fraction in Japan was below those thresholds in 2016, despite the fact that the estimates were above 80% for all ages. If the second dose completely acted as the booster shot, a proportion immune above 90% was achieved only among those aged 5years or below in 2016. Alternatively, if the second dose was randomly distributed regardless of primary vaccination status, a proportion immune over 90% was achieved among those aged below 25years. The effective reproduction number was estimated to range from 1.50 to 3.01 and from 1.50 to 3.00, respectively, for scenarios 1 and 2 in 2016; if the current vaccination schedule were continued, the reproduction number is projected to range from 1.50 to 3.01 and 1.39 to 2.78, respectively, in 2025. Japan continues to be prone to imported cases of measles. Supplementary vaccination among adults aged 20-49years would be effective if the chains of transmission continue to be observed in that age group. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Anomalous scaling in an age-dependent branching model.

    Science.gov (United States)

    Keller-Schmidt, Stephanie; Tuğrul, Murat; Eguíluz, Víctor M; Hernández-García, Emilio; Klemm, Konstantin

    2015-02-01

    We introduce a one-parametric family of tree growth models, in which branching probabilities decrease with branch age τ as τ(-α). Depending on the exponent α, the scaling of tree depth with tree size n displays a transition between the logarithmic scaling of random trees and an algebraic growth. At the transition (α=1) tree depth grows as (logn)(2). This anomalous scaling is in good agreement with the trend observed in evolution of biological species, thus providing a theoretical support for age-dependent speciation and associating it to the occurrence of a critical point.

  14. Qualitative Research in Organizational Studies: Phenomenological Contributions of Alfred Schütz Pesquisa Qualitativa nos Estudos Organizacionais: Contribuições Fenomenológicas de Alfred Schütz

    Directory of Open Access Journals (Sweden)

    Fernando Gomes de Paiva Júnior

    2009-03-01

    Full Text Available Modern science is in crisis. Today, we live in a scientific paradigm transition motivated by differences and complexities. In the organizational field, qualitative research emerges as a methodological alternative to the researcher. It aids the contemporary understanding of the actor involved with the management phenomenon, as it reveals his/her impressions and feelings related to personal and professional lived experiences. The interpretative approach of Alfred Schütz's social phenomenology constitutes one of the variants of the phenomenological movement that makes knowledge of essences possible, and constitutes a type of "intelligible armor" of the organizational being's understanding, which has its structure and specific laws.

  15. The depositional environments of Schöningen 13 II-4 and their archaeological implications.

    Science.gov (United States)

    Stahlschmidt, Mareike C; Miller, Christopher E; Ligouis, Bertrand; Goldberg, Paul; Berna, Francesco; Urban, Brigitte; Conard, Nicholas J

    2015-12-01

    Geoarchaeological research at the Middle Pleistocene site of Schöningen 13 II-4, often referred to as the Speerhorizont, has focused on describing and evaluating the depositional contexts of the well-known wooden spears, butchered horses, and stone tools. These finds were recovered from the transitional contact between a lacustrine marl and an overlying organic mud, originally thought to be a peat that accumulated in place under variable moisture conditions. The original excavators proposed that hominin activity, including hunting and butchery, occurred on a dry lake shore and was followed by a rapid sedimentation of organic deposits that embedded and preserved the artifacts. Our geoarchaeological analysis challenges this model. Here, we present evidence that the sediments of Schöningen 13 II-4 were deposited in a constantly submerged area of a paleolake. Although we cannot exclude the possibility that the artifacts were deposited during a short, extreme drying event, there are no sedimentary features indicative of surface exposure in the sediments. Accordingly, this paper explores three main alternative models of site formation: anthropogenic disposal of materials into the lake, a geological relocation of the artifacts, and hunting or caching on lake-ice. These models have different behavioral ramifications concerning hominin knowledge and exploitation of the landscape and their subsistence strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. From the Pure “We-Relationship” in Schütz to “What Happens Between Us” in Waldenfels: Open Possibilities for an Inclusive Attitude in Relation to the Other

    Directory of Open Access Journals (Sweden)

    Márcio Junglos

    2015-12-01

    Full Text Available This article intends to compare the pure We-relationship in Schütz to what happens between us in Waldenfels. Schütz criticizes Weber’s basic methodological concepts: behavior and rationalism. For Schütz it is impossible through rational observance on relational behavior to guarantee the objectivism of sociology as a science. Schütz tries to prove that only a sociological theory that shows the different realms/worlds from which the interpretation of a product is built, with its obvious limitation of grasping the real meaning, while also clarifying the deep relationship with others, can in fact illustrate its relative anonymity or concreteness. This task involves a sense of searching for concreteness instead of taking for granted its objectiveness. For Waldenfels, the pure We-relationship is too fixed in the subjectivity that is based on one-sided understanding, and decreases possibilities of the event occurring between us. For Schütz, one deals with an eternal paradox of interpretation that will not make us acquainted completely with the other’s mind. The lack of fissure in the We-relationship does not leave space for the possibilities of what happens between us, in other words, the meaning is arrested in subjectivity in an attempt to make meaning as concrete as possible. Waldenfels will not say that the meaning in its integrality can be found, but he will open ways, which lead to a threshold where/elsewhere one will find fissures, new possibilities that first penetrate the body and after can take place in attitudes towards the other.

  17. Predictors of influenza vaccination in the U.S. among children 9-13years of age.

    Science.gov (United States)

    Imburgia, Teresa M; Hendrix, Kristin S; Donahue, Kelly L; Sturm, Lynne A; Zimet, Gregory D

    2017-04-25

    U.S. estimates of seasonal influenza (flu) vaccine uptake in 2014-2015 were 62% for 5-12year olds, dropping to 47% for 13-17year olds. The Healthy People 2020 goal for these age groups is 80%. It is important to understand factors associated with influenza vaccination, especially for those ages where rates begin to decline. The objective of this study was to identify factors associated with influenza vaccination acceptance in 9-13year old children. An online U.S. survey of mothers of children aged 9-13 assessed children's influenza vaccine uptake in the previous season, healthcare utilization, sociodemographics, and vaccine attitudes. Multivariable logistic regression identified independent predictors of influenza vaccine status. There were 2363 respondents (Mean age=38years old). Referent children were 57% female and 66% non-minority race/ethnicity with a mean age of 10.6years. By maternal report, 59% of children had received an influenza vaccine in the previous season. Predictors of influenza vaccine uptake included a recommendation or strong recommendation from a health care provider, seeing a health care provider in the past year, positive attitudes regarding the influenza vaccine, and being a minority race. Child gender, age, insurance coverage, and whether the child had a regular healthcare provider were not associated with influenza vaccine uptake (p=n.s.). This sample reported overall rates of influenza vaccine uptake similar to national surveillance data, but still lower than national goals. Provider recommendations along with health attitudes and seeing a health care provider were associated with vaccine uptake. Promising interventions may include more directive physician messaging for influenza vaccine uptake in youth, encouraging more regular well-child visits during the adolescent years, and promoting influenza vaccination at alternative sites. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. [Occlusion treatment for amblyopia. Age dependence and dose-response relationship].

    Science.gov (United States)

    Fronius, M

    2016-04-01

    Based on clinical experience and studies on animal models the age of 6-7 years was regarded as the limit for treatment of amblyopia, although functional improvement was also occasionally reported in older patients. New technical developments as well as insights from clinical studies and the neurosciences have attracted considerable attention to this topic. Various aspects of the age dependence of amblyopia treatment are discussed in this article, e. g. prescription, electronic monitoring of occlusion dosage, calculation of indicators for age-dependent plasticity of the visual system, and novel, alternative treatment approaches. Besides a discussion of the recent literature, results of studies by our "Child Vision Research Unit" in Frankfurt are presented: results of a questionnaire about prescription habits concerning age limits of patching, electronic recording of occlusion in patients beyond the conventional treatment age, calculation of dose-response function and efficiency of patching and their age dependence. The results of the questionnaire illustrate the uncertainty about age limits of prescription with significant deviations from the guideline of the German Ophthalmological Society (DOG). Electronic recording of occlusion allowed the quantification of declining dose-response function and treatment efficiency between 5 and 16 years of age. Reports about successful treatment with conventional and novel methods in adults are at variance with the notion of a rigid adult visual system lacking plasticity. Electronic recording of patching allowed new insights into the age-dependent susceptibility of the visual system and contributes to a more evidence-based treatment of amblyopia. Alternative approaches for adults challenge established notions about age limits of amblyopia therapy. Further studies comparing different treatment options are urgently needed.

  19. ANATOMY OF GYNURA AURANTIACA (BLUME SCH.BIP. EX DC. (ASTERACEAE

    Directory of Open Access Journals (Sweden)

    Rodica BERCU

    2014-06-01

    Full Text Available The paper presents a detailed histoanatomical description, of the vegetative organs (root, stem and leaf and photographs as well of Gynura aurantiaca (Blume Sch.Bip. ex DC. It was observed that the root have typical primary dictos structure. The stem has a differentiated in two regions cortex and the stele comprise one ring of open collateral vascular bundles with secondary xylem due to the cambium activity. The petiole anatomy is quite similar in its basic structure with the stem. The blade presents a heterogenous and hypostomatic mesophyll and a number of vascular bundles in the midrib zone. Remarkable is the presence of the filamentous, uniseriate non-glandular hairs in the stem, petiole and leaf blade. The mechanical tissue is present in the stem, petiole and blade as well.

  20. High efficiency of targeted mutagenesis in arabidopsis via meiotic promoter-driven expression of Cas9 endonuclease

    KAUST Repository

    Eid, Ayman

    2016-05-28

    Key message: The use of a meiosis I-specific promoter increased the efficiency of targeted mutagenesis and will facilitate the manipulation of homologous recombination. Abstract: The CRISPR/Cas9 system has been harnessed for targeted engineering of eukaryotic genomes, including plants; however, CRISPR/Cas9 efficiency varies considerably in different plant tissues and species. In Arabidopsis, the generation of homozygous or bi-allelic mutants in the first (T1) generation is inefficient. Here, we used specific promoters to drive the expression of Cas9 during meiosis to maximize the efficiency of recovering heritable mutants in T1 plants. Our data reveal that the use of a promoter active in meiosis I resulted in high-efficiency (28 %) recovery of targeted mutants in the T1 generation. Moreover, this method enabled efficient simultaneous targeting of three genes for mutagenesis. Taken together, our results show that the use of meiosis-specific promoters will improve methods for functional genomic analysis and studying the molecular underpinnings of homologous recombination. © 2016, Springer-Verlag Berlin Heidelberg.

  1. Age Spreads and the Temperature Dependence of Age Estimates in Upper Sco

    Energy Technology Data Exchange (ETDEWEB)

    Fang Qiliang; Herczeg, Gregory J. [Kavli Institute for Astronomy and Astrophysics, Peking University, Yiheyuan Lu 5, Haidian Qu, 100871 Beijing (China); Rizzuto, Aaron [Department of Astronomy, University of Texas, 2515 Speedway, Stop C1400, Austin, TX 78712 (United States)

    2017-06-20

    Past estimates for the age of the Upper Sco Association are typically 11–13 Myr for intermediate-mass stars and 4–5 Myr for low-mass stars. In this study, we simulate populations of young stars to investigate whether this apparent dependence of estimated age on spectral type may be explained by the star formation history of the association. Solar and intermediate mass stars begin their pre-main sequence evolution on the Hayashi track, with fully convective interiors and cool photospheres. Intermediate-mass stars quickly heat up and transition onto the radiative Henyey track. As a consequence, for clusters in which star formation occurs on a timescale similar to that of the transition from a convective to a radiative interior, discrepancies in ages will arise when ages are calculated as a function of temperature instead of mass. Simple simulations of a cluster with constant star formation over several Myr may explain about half of the difference in inferred ages versus photospheric temperature; speculative constructions that consist of a constant star formation followed by a large supernova-driven burst could fully explain the differences, including those between F and G stars where evolutionary tracks may be more accurate. The age spreads of low-mass stars predicted from these prescriptions for star formation are consistent with the observed luminosity spread of Upper Sco. The conclusion that a lengthy star formation history will yield a temperature dependence in ages is expected from the basic physics of pre-main sequence evolution, and is qualitatively robust to the large uncertainties in pre-main sequence evolutionary models.

  2. Vertical Jump and Leg Power Normative Data for Colombian Schoolchildren Aged 9-17.9 Years: The FUPRECOL Study.

    Science.gov (United States)

    Ramírez-Vélez, Robinson; Correa-Bautista, Jorge E; Lobelo, Felipe; Cadore, Eduardo L; Alonso-Martinez, Alicia M; Izquierdo, Mikel

    2017-04-01

    Ramírez-Vélez, R, Correa-Bautista, JE, Lobelo, F, Cadore, EL, Alonso-Martinez, AM, and Izquierdo, M. Vertical jump and leg power normative data for Colombian schoolchildren aged 9-17.9 years: the FUPRECOL study. J Strength Cond Res 31(4): 990-998, 2017-The aims of the present study were to generate normative vertical jump height and predicted peak power (Ppeak) data for 9- to 17.9-year-olds and to investigate between-sex and age group differences in these measures. This was a cross-sectional study of 7,614 healthy schoolchildren (boys n = 3,258 and girls n = 4,356, mean [SD] age 12.8 [2.3] years). Each participant performed 2 countermovement jumps; jump height was calculated using a Takei 5414 Jump-DF Digital Vertical (Takei Scientific Instruments Co., Ltd.). The highest jump was used for analysis and in the calculation of predicted Ppeak. Centile smoothed curves, percentiles, and tables for the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles were calculated using Cole's LMS (L [curve Box-Cox], M [curve median], and S [curve coefficient of variation]) method. The 2-way analysis of variance tests showed that maximum jump height (in centimeters) and predicted Ppeak (in watts) were higher in boys than in girls (p jump height and Ppeak in all ages. In boys, the maximum jump height and predicted Ppeak 50th percentile ranged from 24.0 to 38.0 cm and from 845.5 to 3061.6 W, respectively. In girls, the 50th percentile for jump height ranged from 22.3 to 27.0 cm, and the predicted Ppeak was 710.1-2036.4 W. For girls, jump height increased yearly from 9 to 17.9 years old. Our results provide, for the first time, sex- and age-specific vertical jump height and predicted Ppeak reference standards for Colombian schoolchildren aged 9-17.9 years.

  3. CDK9-dependent RNA polymerase II pausing controls transcription initiation.

    Science.gov (United States)

    Gressel, Saskia; Schwalb, Björn; Decker, Tim Michael; Qin, Weihua; Leonhardt, Heinrich; Eick, Dirk; Cramer, Patrick

    2017-10-10

    Gene transcription can be activated by decreasing the duration of RNA polymerase II pausing in the promoter-proximal region, but how this is achieved remains unclear. Here we use a 'multi-omics' approach to demonstrate that the duration of polymerase pausing generally limits the productive frequency of transcription initiation in human cells ('pause-initiation limit'). We further engineer a human cell line to allow for specific and rapid inhibition of the P-TEFb kinase CDK9, which is implicated in polymerase pause release. CDK9 activity decreases the pause duration but also increases the productive initiation frequency. This shows that CDK9 stimulates release of paused polymerase and activates transcription by increasing the number of transcribing polymerases and thus the amount of mRNA synthesized per time. CDK9 activity is also associated with long-range chromatin interactions, suggesting that enhancers can influence the pause-initiation limit to regulate transcription.

  4. Ciência e tecnologia no Brasil Imperial Guilherme Schüch, Barão de Capanema (1824-1908 Science and technology in Imperial Brazil Guilherme Schüch, Baron of Capanema (1824-1908

    Directory of Open Access Journals (Sweden)

    Silvia Fernanda de Mendonça Figueirôa

    2005-07-01

    Full Text Available O engenheiro e naturalista Guilherme Schüch de Capanema foi, sem dúvida, um expoente da elite Imperial. Circulou por importantes espaços institucionais científicos e técnicos, tendo atuado de forma bastante significativa para a implementação de uma cultura técnico-científica no Brasil e o conseqüente fortalecimento da engenharia e dos engenheiros. Entretanto, Capanema ainda permanece, assim como quase todos os cientistas do Segundo Império, um "desconhecido mal conhecido". O presente trabalho, contudo, não se propõe fazer sua extensa biografia, mas analisar e ressaltar aspectos de sua obra, relacionandoos a sua formação universitária e a sua prática enquanto engenheiro e naturalista.Guilherme Schüch de Capanema was a prominent member of the Brazilian imperial elite. He belonged to several important institutional loci giving his valuable contribution to the implementation of a technical-scientific culture in Brazil, and therefore to the strengthening of both the field of engineering and the engineers. However, Capanema still remains an .unknown not well known., as do the majority of the scientists of the Second Empire. This paper analyzes and stresses aspects of his professional and academic life, related to his university education, and to his practice as engineer and naturalist.

  5. Establishing a Proper Model of Tobacco Dependence: Influence of Age and Tobacco Smoke Constituents

    OpenAIRE

    Gellner, Candice Ann

    2017-01-01

    Cigarette smoking is the leading preventable cause of death in the United States. Of those who smoke, 9 out of 10 report trying their first cigarette before the age of 18. Although most people who initiate tobacco use are teenagers, animal models for studying tobacco dependence have traditionally focused on how adult animals initiate, withdrawal from and relapse to cigarette smoking. Furthermore, cigarette smoke contains more than 7,000 constituents, including nicotine, yet pre-clinical resea...

  6. A Novel Series of Highly Potent 2,6,9-Trisubstituted Purine Cyclin-Dependent Kinase Inhibitors

    Czech Academy of Sciences Publication Activity Database

    Gucký, T.; Jorda, Radek; Zatloukal, M.; Bazgier, V.; Berka, K.; Řezníčková, Eva; Béres, T.; Strnad, Miroslav; Kryštof, Vladimír

    2013-01-01

    Roč. 56, č. 15 (2013), s. 6234-6247 ISSN 0022-2623 R&D Projects: GA ČR GAP305/12/0783; GA ČR GD203/09/H046 Grant - others:GA MŠk(CZ) ED0007/01/01; GA MŠk(CZ) ED2.1.00/03.0058; GA MŠk(CZ) EE2.3.20.0017 Program:ED; ED; EE Institutional research plan: CEZ:AV0Z50380511 Keywords : CHRONIC LYMPHOCYTIC- LEUKEMIA * DINACICLIB SCH 727965 * CELL-CYCLE Subject RIV: ED - Physiology Impact factor: 5.480, year: 2013

  7. [Henoch-Schönlein Purpura with lung abscess].

    Science.gov (United States)

    Nakazawa, Junji; Watanabe, Atsushi; Nakajima, Tomohiro; Mishina, Taijiro; Miyajima, Masahiro; Higami, Tetsuya

    2013-09-01

    A 72-year-old man had underwent left lower lobectomy for squamous cell carcinoma in our hospital in 2008. Postoperative stage was I A (T1N0M0). In 2010, follow-up chest computed tomography (CT) images showed similar cavitary nodules in segments 2 and 8 of the right lung with positive uptake on fluorodeoxyglucose-positron emission tomography (FDG-PET) images. Physical examination, blood tests, and levels of serum tumor markers showed no abnormality. Transbronchial lung biopsy revealed the absence of malignant cells. Segment 8 of the right lower lobe with the nodule was partially resected, and pathological examination demonstrated lung abscess. He was discharged but was hospitalized in another hospital for purpuric rash, fever, and arthralgia. Microscopic albuminuria was noted, and renal biopsy revealed nephritis with immunoglobulin A( IgA)deposition. He was made a diagnosis of Henoch-Schönlein purpura. Oral steroid therapy( prednisolone 60 mg/d) was initiated, resulting in the improvement of symptoms and disapearance of the cavitary nodule in the right lung segment 2.

  8. G9a stimulates CRC growth by inducing p53 Lys373 dimethylation-dependent activation of Plk1.

    Science.gov (United States)

    Zhang, Jie; Wang, Yafang; Shen, Yanyan; He, Pengxing; Ding, Jian; Chen, Yi

    2018-01-01

    Rationale: G9a is genetically deregulated in various tumor types and is important for cell proliferation; however, the mechanism underlying G9a-induced carcinogenesis, especially in colorectal cancer (CRC), is unclear. Here, we investigated if G9a exerts oncogenic effects in CRC by increasing polo-like kinase 1 (Plk1) expression. Thus, we further characterized the detailed molecular mechanisms. Methods: The role of Plk1 in G9a aberrant CRC was determined by performing different in vitro and in vivo assays, including assessment of cell growth by performing cell viability assay and assessment of signaling transduction profiles by performing immunoblotting, in the cases of pharmacological inhibition or short RNA interference-mediated suppression of G9a. Detailed molecular mechanisms underlying the effect of G9a on Plk1 expression were determined by performing point mutation analysis, chromatin immunoprecipitation analysis, and luciferase reporter assay. Correlation between G9a and Plk1 expression was determined by analyzing clinical samples of patients with CRC by performing immunohistochemistry. Results: Our study is the first to report a significant positive correlation between G9a and Plk1 levels in 89 clinical samples of patients with CRC. Moreover, G9a depletion decreased Plk1 expression and suppressed CRC cell growth both in vitro and in vivo , thus confirming the significant correlation between G9a and Plk1 levels. Further, we observed that G9a-induced Plk1 regulation depended on p53 inhibition. G9a dimethylated p53 at lysine 373, which in turn increased Plk1 expression and promoted CRC cell growth. Conclusions: These results indicate that G9a-induced and p53-dependent epigenetic programing stimulates the growth of colon cancer, which also suggests that G9a inhibitors that restore p53 activity are promising therapeutic agents for treating colon cancer, especially for CRC expressing wild-type p53.

  9. Wertigkeit der Schnittbilddiagnostik in der Evaluation des pädiatrischen Schädel-Hirn-Traumas

    OpenAIRE

    Schäffeler, Christoph

    2010-01-01

    Die vorliegende Arbeit untersucht die diagnostische Wertigkeit von Computertomographie (CT) und Magnetresonanztomographie (MRT) in der Diagnostik des pädiatrischen Schädel-Hirn-Traumas. In einer retrospektiven Auswertung der Bildgebung von 64 Patienten im Alter von 0-15 Jahren wurden die Vor- und Nachteile der CT und MRT - Diagnostik bei der Darstellung intrakranieller Traumfolgen herausgearbeitet. Die Ergebnisse räumen der CT weiterhin einen hohen Stellenwert in der Akutdiagnostik ein, zeige...

  10. Anti-alpha-galactosyl antibodies and immune complexes in children with Henoch-Schönlein purpura or IgA nephropathy

    NARCIS (Netherlands)

    Davin, J. C.; Malaise, M.; Foidart, J.; Mahieu, P.

    1987-01-01

    Episodes of hematuria in IgA nephropathy or Henoch-Schönlein purpura are frequently associated with microbial infections. Some of those infectious agents bear alpha-galactosyl residues on their cell surface. These observations prompted us to determine, by passive hemagglutination, the titers of

  11. Muusikamaailm : Milano La Scala sulgeb uksed. Schönberg ja Kandinsky. Preemiaid ja tunnustusi. Witold Szalonek lahkunud. / Priit Kuusk

    Index Scriptorium Estoniae

    Kuusk, Priit, 1938-

    2002-01-01

    Milano La Scala suletakse kaheks aastaks ümberehituseks ja renoveerimiseks. Moskvas toimub näitus ja kontserdisari "Schönberg ja Kandinsky ئ maalikunst ja muusika dialoogis". Erinevaid preemiaid ja tunnustusi saanud muusikad. 74aastasena suri Berliinis nimekas poola helilooja, pianist ja pedagoog Witold Szalonek

  12. Set2 Methyltransferase Facilitates DNA Replication and Promotes Genotoxic Stress Responses through MBF-Dependent Transcription.

    Science.gov (United States)

    Pai, Chen-Chun; Kishkevich, Anastasiya; Deegan, Rachel S; Keszthelyi, Andrea; Folkes, Lisa; Kearsey, Stephen E; De León, Nagore; Soriano, Ignacio; de Bruin, Robertus Antonius Maria; Carr, Antony M; Humphrey, Timothy C

    2017-09-12

    Chromatin modification through histone H3 lysine 36 methylation by the SETD2 tumor suppressor plays a key role in maintaining genome stability. Here, we describe a role for Set2-dependent H3K36 methylation in facilitating DNA replication and the transcriptional responses to both replication stress and DNA damage through promoting MluI cell-cycle box (MCB) binding factor (MBF)-complex-dependent transcription in fission yeast. Set2 loss leads to reduced MBF-dependent ribonucleotide reductase (RNR) expression, reduced deoxyribonucleoside triphosphate (dNTP) synthesis, altered replication origin firing, and a checkpoint-dependent S-phase delay. Accordingly, prolonged S phase in the absence of Set2 is suppressed by increasing dNTP synthesis. Furthermore, H3K36 is di- and tri-methylated at these MBF gene promoters, and Set2 loss leads to reduced MBF binding and transcription in response to genotoxic stress. Together, these findings provide new insights into how H3K36 methylation facilitates DNA replication and promotes genotoxic stress responses in fission yeast. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Set2 Methyltransferase Facilitates DNA Replication and Promotes Genotoxic Stress Responses through MBF-Dependent Transcription

    Directory of Open Access Journals (Sweden)

    Chen-Chun Pai

    2017-09-01

    Full Text Available Chromatin modification through histone H3 lysine 36 methylation by the SETD2 tumor suppressor plays a key role in maintaining genome stability. Here, we describe a role for Set2-dependent H3K36 methylation in facilitating DNA replication and the transcriptional responses to both replication stress and DNA damage through promoting MluI cell-cycle box (MCB binding factor (MBF-complex-dependent transcription in fission yeast. Set2 loss leads to reduced MBF-dependent ribonucleotide reductase (RNR expression, reduced deoxyribonucleoside triphosphate (dNTP synthesis, altered replication origin firing, and a checkpoint-dependent S-phase delay. Accordingly, prolonged S phase in the absence of Set2 is suppressed by increasing dNTP synthesis. Furthermore, H3K36 is di- and tri-methylated at these MBF gene promoters, and Set2 loss leads to reduced MBF binding and transcription in response to genotoxic stress. Together, these findings provide new insights into how H3K36 methylation facilitates DNA replication and promotes genotoxic stress responses in fission yeast.

  14. EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part I: Overall methodology and clinical characterisation

    DEFF Research Database (Denmark)

    Ruperto, Nicolino; Ozen, Seza; Pistorio, Angela

    2010-01-01

    To report methodology and overall clinical, laboratory and radiographic characteristics for Henoch-Schönlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA) classification criteria.......To report methodology and overall clinical, laboratory and radiographic characteristics for Henoch-Schönlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA) classification criteria....

  15. Range of variation of genu valgum and association with anthropometric characteristics and physical activity: comparison between children aged 3-9 years.

    Science.gov (United States)

    Kaspiris, Angelos; Zaphiropoulou, Chrisi; Vasiliadis, Elias

    2013-07-01

    The lower limbs of children aged 3-9 years present varying knock-knee deformities that have a direct impact on the diversification of the load-bearing axis of the valgus limb and on the modification of gait kinematics. The purpose of our study was to establish the reference values of knee alignment in a Greek population and whether this is linked to a change in the physical activity of children depending on the severity of the genu valgum. Using a clinical method, we measured both the tibiofemoral (TF) angle and the intermalleolar (IM) distance of the lower extremities of normal children. Subsequently, forms of the Netherlands Physical Activity Questionnaire (NPAQ) for young children and the Baecke questionnaire on habitual physical activity, modified especially for children, were completed by the parents. We examined both the development of the TF angle and the IM distance in relation to age and the degree of restriction of physical activity in relation to the severity of the genu valgum. We analysed 316 unaffected lower extremities in children aged 3-9 years. The average value of the TF angle starts around 7° at the age of 3 years and gradually decreases to 4° at the age of 7-8 years. The average value of the IM distance ranges over 3.5 cm at the age of 3 years and progressively decreases to 2 cm at the age of 7-8 years. Physical activity appears to be influenced by sex and the severity of the genu valgum. We provide age-specific values for limb alignment and joint orientation of the lower extremity in children aged 3-9 years. A statistical correlation between all indexes (sport, leisure time and total) of the Baecke and the NPAQs and measurements of genu valgum was noted depending on the severity of the valgus deformity.

  16. A receptor tyrosine kinase inhibitor, Tyrphostin A9 induces cancer cell death through Drp1 dependent mitochondria fragmentation

    International Nuclear Information System (INIS)

    Park, So Jung; Park, Young Jun; Shin, Ji Hyun; Kim, Eun Sung; Hwang, Jung Jin; Jin, Dong-Hoon; Kim, Jin Cheon; Cho, Dong-Hyung

    2011-01-01

    Highlights: → We screened and identified Tyrphostin A9, a receptor tyrosine kinase inhibitor as a strong mitochondria fission inducer. → Tyrphostin A9 treatment promotes mitochondria dysfunction and contributes to cytotoxicity in cancer cells. → Tyrphostin A9 induces apoptotic cell death through a Drp1-mediated pathway. → Our studies suggest that Tyrphostin A9 induces mitochondria fragmentation and apoptotic cell death via Drp1 dependently. -- Abstract: Mitochondria dynamics controls not only their morphology but also functions of mitochondria. Therefore, an imbalance of the dynamics eventually leads to mitochondria disruption and cell death. To identify specific regulators of mitochondria dynamics, we screened a bioactive chemical compound library and selected Tyrphostin A9, a tyrosine kinase inhibitor, as a potent inducer of mitochondrial fission. Tyrphostin A9 treatment resulted in the formation of fragmented mitochondria filament. In addition, cellular ATP level was decreased and the mitochondrial membrane potential was collapsed in Tyr A9-treated cells. Suppression of Drp1 activity by siRNA or over-expression of a dominant negative mutant of Drp1 inhibited both mitochondrial fragmentation and cell death induced by Tyrpohotin A9. Moreover, treatment of Tyrphostin A9 also evoked mitochondrial fragmentation in other cells including the neuroblastomas. Taken together, these results suggest that Tyrphostin A9 induces Drp1-mediated mitochondrial fission and apoptotic cell death.

  17. Does employee participation in workplace health promotion depend on the working environment?

    DEFF Research Database (Denmark)

    Jørgensen, Marie Birk; Villadsen, Ebbe; Burr, Hermann

    2016-01-01

    OBJECTIVES: To investigate if participation in workplace health promotion (WHP) depends on the work environment. METHODS: Questionnaire data on participation in WHP activities (smoking cessation, healthy diet, exercise facilities, weekly exercise classes, contact with health professionals, health...

  18. Subclinical hypothyroidism is associated with increased risk for cancer mortality in adult Taiwanese-a 10 years population-based cohort.

    Directory of Open Access Journals (Sweden)

    Fen-Yu Tseng

    Full Text Available The association between subclinical hypothyroidism (SCH and cancer mortality is seldom discussed.A total of 115,746 participants without thyroid disease history, aged 20 and above, were recruited from four nationwide health screening centers in Taiwan from 1998 to 1999. SCH was defined as a serum thyroid-stimulating hormone (TSH level of 5.0-19.96 mIU/L with normal total thyroxine concentrations. Euthyroidism was defined as a serum TSH level of 0.47-4.9 mIU/L. Cox proportional hazards regression analyses were used to estimate the relative risks (RRs of death from cancer for adults with SCH during a 10-year follow-up period.Among 115,746 adults, 1,841 had SCH (1.6% and 113,905 (98.4% had euthyroidism. There were 1,532 cancer deaths during the 1,034,082 person-years follow-up period. Adjusted for age, gender, body mass index, diabetes, hypertension, dyslipidemia, smoking, alcohol drinking, betel nut chewing, physical activity, income, and education level, the RRs (95% confidence interval of cancer deaths among subjects with SCH versus euthyroid subjects were 1.51 (1.06 to 2.15. Cancer site analysis revealed a significant increased risk of bone, skin and breast cancer among SCH subjects (RR 2.79, (1.01, 7.70. The risks of total cancer deaths were more prominent in the aged (RR 1.71, (1.02 to 2.87, in females (RR 1.69 (1.08 to 2.65, and in heavy smokers (RR 2.24, (1.19 to 4.21.Subjects with SCH had a significantly increased risk for cancer mortality among adult Taiwanese. This is the first report to demonstrate the association between SCH and cancer mortality.

  19. Subclinical hypothyroidism is associated with increased risk for cancer mortality in adult Taiwanese-a 10 years population-based cohort.

    Science.gov (United States)

    Tseng, Fen-Yu; Lin, Wen-Yuan; Li, Chia-Ing; Li, Tsai-Chung; Lin, Cheng-Chieh; Huang, Kuo-Chin

    2015-01-01

    The association between subclinical hypothyroidism (SCH) and cancer mortality is seldom discussed. A total of 115,746 participants without thyroid disease history, aged 20 and above, were recruited from four nationwide health screening centers in Taiwan from 1998 to 1999. SCH was defined as a serum thyroid-stimulating hormone (TSH) level of 5.0-19.96 mIU/L with normal total thyroxine concentrations. Euthyroidism was defined as a serum TSH level of 0.47-4.9 mIU/L. Cox proportional hazards regression analyses were used to estimate the relative risks (RRs) of death from cancer for adults with SCH during a 10-year follow-up period. Among 115,746 adults, 1,841 had SCH (1.6%) and 113,905 (98.4%) had euthyroidism. There were 1,532 cancer deaths during the 1,034,082 person-years follow-up period. Adjusted for age, gender, body mass index, diabetes, hypertension, dyslipidemia, smoking, alcohol drinking, betel nut chewing, physical activity, income, and education level, the RRs (95% confidence interval) of cancer deaths among subjects with SCH versus euthyroid subjects were 1.51 (1.06 to 2.15). Cancer site analysis revealed a significant increased risk of bone, skin and breast cancer among SCH subjects (RR 2.79, (1.01, 7.70)). The risks of total cancer deaths were more prominent in the aged (RR 1.71, (1.02 to 2.87)), in females (RR 1.69 (1.08 to 2.65)), and in heavy smokers (RR 2.24, (1.19 to 4.21)). Subjects with SCH had a significantly increased risk for cancer mortality among adult Taiwanese. This is the first report to demonstrate the association between SCH and cancer mortality.

  20. Paleoenvironment and possibilities of plant exploitation in the Middle Pleistocene of Schöningen (Germany). Insights from botanical macro-remains and pollen.

    Science.gov (United States)

    Bigga, Gerlinde; Schoch, Werner H; Urban, Brigitte

    2015-12-01

    Plant use is an elusive issue in Paleolithic archaeology. Due to poor organic preservation in many sites, botanical material is not always present. The sediments in Schöningen, however, contain abundant botanical macro-remains like wood, fruits, seeds, and other parts of plants which offer the opportunity to reconstruct the local vegetation. Combined with palynological results, it is possible to reveal the full potential of this environment to hominins. Ethnobotanical studies of hunter-gatherer societies living in similar environments illustrate the importance of plants for subsistence purposes. The identified taxa from the archaeological horizons at Schöningen include a broad spectrum of potentially exploitable species that could be sources of food, raw material, and firewood. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. The role of age, gender, mood states and exercise frequency on exercise dependence.

    Science.gov (United States)

    Costa, Sebastiano; Hausenblas, Heather A; Oliva, Patrizia; Cuzzocrea, Francesca; Larcan, Rosalba

    2013-12-01

    The purpose of our study was to explore the prevalence, and the role of mood, exercise frequency, age, and gender differences of exercise dependence. Regular exercisers (N = 409) completed a socio-demographic questionnaire, the Exercise Dependence Scale, and the Profile of Mood States. For data analyses, the participants were stratified for sex and age (age ranges = young adults: 18-24 years, adults: 25-44 years, and middle-aged adults: 45-64 years). We found that: (a) 4.4% of the participants were classified as at-risk for exercise dependence; (b) the men and the two younger groups (i.e., young adults and adults) had higher exercise dependence scores; and (c) age, gender, exercise frequency, and mood state were related to exercise dependence. Our results support previous research on the prevalence of exercise dependence and reveal that adulthood may be the critical age for developing exercise dependence. These findings have practical implication for identifying individuals at-risk for exercise dependence symptoms, and may aid in targeting and guiding the implementation of prevention program for adults.

  2. Sex-specific effects of TLR9 promoter variants on spontaneous clearance of HCV infection.

    Science.gov (United States)

    Fischer, Janett; Weber, Alexander N R; Böhm, Stephan; Dickhöfer, Sabine; El Maadidi, Souhayla; Deichsel, Danilo; Knop, Viola; Klinker, Hartwig; Möller, Bernd; Rasenack, Jens; Wang, Lisa; Sharma, Manu; Hinrichsen, Holger; Spengler, Ulrich; Buggisch, Peter; Sarrazin, Christoph; Pawlita, Michael; Waterboer, Tim; Wiese, Manfred; Probst-Müller, Elsbeth; Malinverni, Raffaele; Bochud, Pierre-Yves; Gardiner, Clair; O'Farrelly, Cliona; Berg, Thomas

    2017-10-01

    As pathogen sensors, Toll-like receptors (TLR) play a role in the first defence line during HCV infection. However, the impact of the DNA sensor TLR9 on the natural course of HCV infection is unknown. To address this, TLR9 promoter polymorphisms (single nucleotide polymorphisms (SNPs)) rs187084 and rs5743836 were investigated for their effect on disease progression. Therefore, the TLR9 SNPs and the interferon lambda 4 ( IFNL4 ) rs12979860 were genotyped in chronically HCV type 1 infected (n=333), in patients who spontaneously cleared the infection (n=161), in the Swiss HCV cohort (n=1057) and the well-characterised German (n=305) and Irish (n=198) 'anti-D' cohorts. Functional analyses were done with promoter reporter constructs of human TLR9 in B cells and assessing TLR9 mRNA levels in whole blood of healthy volunteers. The TLR9 rs187084 C allele was associated with spontaneous virus clearance in women of the study cohort (OR=2.15 (95% CI 1.18 to 3.90) p=0.012), of the Swiss HCV cohort (OR=2.06 (95% CI 1.02 to 4.18) p=0.044) and in both 'anti-D' cohorts (German: OR=2.01 (95% CI 1.14 to 3.55) p=0.016; Irish: OR=1.93 (95% CI 1.10 to 3.68) p=0.047). Multivariate analysis in the combined study and Swiss HCV cohorts supported the results (OR=1.99 (95% CI 1.30 to 3.05) p=0.002). Functional analyses revealed higher transcriptional activities for both TLR9 variants and an association of the C allele of rs5743836 with allele-specific TLR9 mRNA regulation by oestrogens in women. TLR9 promoter SNPs are associated with the natural course of HCV infection and show higher transcriptional activities. Our results imply the DNA sensor TLR9 in natural immunity against the RNA virus, HCV. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  3. Time-dependent density functional theory study of the luminescence properties of gold phosphine thiolate complexes.

    Science.gov (United States)

    Guidez, Emilie B; Aikens, Christine M

    2015-04-09

    The origin of the emission of the gold phosphine thiolate complex (TPA)AuSCH(CH3)2 (TPA = 1,3,5-triaza-7-phosphaadamantanetriylphosphine) is investigated using time-dependent density functional theory (TDDFT). This system absorbs light at 3.6 eV, which corresponds mostly to a ligand-to-metal transition with some interligand character. The P-Au-S angle decreases upon relaxation in the S1 and T1 states. Our calculations show that these two states are strongly spin-orbit coupled at the ground state geometry. Ligand effects on the optical properties of this complex are also discussed by looking at the simple AuP(CH3)3SCH3 complex. The excitation energies differ by several tenths of an electronvolt. Excited state optimizations show that the excited singlet and triplet of the (TPA)AuSCH(CH3)2 complex are bent. On the other hand, the Au-S bond breaks in the excited state for the simple complex, and TDDFT is no longer an adequate method. The excited state energy landscape of gold phosphine thiolate systems is very complex, with several state crossings. This study also shows that the formation of the [(TPA)AuSCH(CH3)2]2 dimer is favorable in the ground state. The inclusion of dispersion interactions in the calculations affects the optimized geometries of both ground and excited states. Upon excitation, the formation of a Au-Au bond occurs, which results in an increase in energy of the low energy excited states in comparison to the monomer. The experimentally observed emission of the (TPA)AuSCH(CH3)2 complex at 1.86 eV cannot be unambiguously assigned and may originate from several excited states.

  4. Heart Age PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2015-09-01

    This 60 second public service announcement is based on the September 2015 CDC Vital Signs report. Your heart age is the age of your heart and blood vessels as a result of your risk factors for heart attack and stroke. If you smoke or have high blood pressure, your heart age will be much higher than your actual age. Learn what you can do to lower your heart age and keep it low.  Created: 9/1/2015 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 9/1/2015.

  5. Load-related brain activation predicts spatial working memory performance in youth aged 9–12 and is associated with executive function at earlier ages

    Science.gov (United States)

    Huang, Anna S.; Klein, Daniel N.; Leung, Hoi-Chung

    2015-01-01

    Spatial working memory is a central cognitive process that matures through adolescence in conjunction with major changes in brain function and anatomy. Here we focused on late childhood and early adolescence to more closely examine the neural correlates of performance variability during this important transition period. Using a modified spatial 1-back task with two memory load conditions in an fMRI study, we examined the relationship between load-dependent neural responses and task performance in a sample of 39 youth aged 9–12 years. Our data revealed that between-subject differences in task performance was predicted by load-dependent deactivation in default network regions, including the ventral anterior cingulate cortex (vACC) and posterior cingulate cortex (PCC). Although load-dependent increases in activation in prefrontal and posterior parietal regions were only weakly correlated with performance, increased prefrontal-parietal coupling was associated with better performance. Furthermore, behavioral measures of executive function from as early as age 3 predicted current load-dependent deactivation in vACC and PCC. These findings suggest that both task positive and task negative brain activation during spatial working memory contributed to successful task performance in late childhood/early adolescence. This may serve as a good model for studying executive control deficits in developmental disorders. PMID:26562059

  6. Rab9-dependent retrograde transport and endosomal sorting of the endopeptidase furin

    Science.gov (United States)

    Chia, Pei Zhi Cheryl; Gasnereau, Isabelle; Lieu, Zi Zhao; Gleeson, Paul A.

    2011-01-01

    The endopeptidase furin and the trans-Golgi network protein TGN38 are membrane proteins that recycle between the TGN and plasma membrane. TGN38 is transported by a retromer-dependent pathway from early endosomes to the TGN, whereas the intracellular transport of furin is poorly defined. Here we have identified the itinerary and transport requirements of furin. Using internalisation assays, we show that furin transits the early and late endosomes en route to the TGN. The GTPase Rab9 and the TGN golgin GCC185, components of the late endosome-to-TGN pathway, were required for efficient TGN retrieval of furin. By contrast, TGN38 trafficking was independent of Rab9 and GCC185. To identify the sorting signals for the early endosome-to-TGN pathway, the trafficking of furin–TGN38 chimeras was investigated. The diversion of furin from the Rab9-dependent late-endosome-to-TGN pathway to the retromer-dependent early-endosome-to-TGN pathway required both the transmembrane domain and cytoplasmic tail of TGN38. We present evidence to suggest that the length of the transmembrane domain is a contributing factor in endosomal sorting. Overall, these data show that furin uses the Rab9-dependent pathway from late endosomes and that retrograde transport directly from early endosomes is dependent on both the transmembrane domain and the cytoplasmic tail. PMID:21693586

  7. A review of age dependent radioiodine dosimetry

    International Nuclear Information System (INIS)

    Johnson, J.R.

    1987-01-01

    Age dependent models of radioiodine metabolism in humans have been described. These models have been used to calculate age dependent committed doses to the thyroid from intakes of radioiodines. A model of fetal iodine metabolism is also described and used to calculate fetal thyroid doses from intakes of radioiodines by the mother. These doses are calculated using model parameter values thought to be representative of average for North American/European populations. Considerable variability from these results can be expected for individuals. In addition, population with significant differences in stable iodine intake, and in body parameters, will have model parameters somewhat different than the ones described in this paper. These different model parameters will result in different doses from intakes of radioiodines, but it is doubtful if the differences in population would be as large as the variation between individuals. 25 refs.; 11 figs.; 1 table

  8. Mediator subunit MED1 is a T3-dependent and T3-independent coactivator on the thyrotropin β gene promoter

    Energy Technology Data Exchange (ETDEWEB)

    Matsui, Keiji; Oda, Kasumi; Mizuta, Shumpei; Ishino, Ruri; Urahama, Norinaga; Hasegawa, Natsumi [Laboratory of Hematology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142 (Japan); Roeder, Robert G. [Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065 (United States); Ito, Mitsuhiro, E-mail: itomi@med.kobe-u.ac.jp [Laboratory of Hematology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142 (Japan); Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065 (United States); Department of Family and Community Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 654-0142 (Japan); Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 159-8555 (Japan)

    2013-10-11

    Highlights: •MED1 is a bona fide T3-dependent coactivator on TSHB promoter. •Mice with LxxLL-mutant MED1 have attenuated TSHβ mRNA and thyroid hormone levels. •MED1 activates TSHB promoter T3-dependently in cultured cells. •T3-dependent MED1 action is enhanced when SRC1/SRC2 or HDAC2 is downregulated. •MED1 is also a T3-independent GATA2/Pit1 coactivator on TSHB promoter. -- Abstract: The MED1 subunit of the Mediator transcriptional coregulator complex is a nuclear receptor-specific coactivator. A negative feedback mechanism of thyroid-stimulating hormone (TSH, or thyrotropin) expression in the thyrotroph in the presence of triiodothyronine (T3) is employed by liganded thyroid hormone receptor β (TRβ) on the TSHβ gene promoter, where conventional histone-modifying coactivators act as corepressors. We now provide evidence that MED1 is a ligand-dependent positive cofactor on this promoter. TSHβ gene transcription was attenuated in MED1 mutant mice in which the nuclear receptor-binding ability of MED1 was specifically disrupted. MED1 stimulated GATA2- and Pit1-mediated TSHβ gene promoter activity in a ligand-independent manner in cultured cells. MED1 also stimulated transcription from the TSHβ gene promoter in a T3-dependent manner. The transcription was further enhanced when the T3-dependent corepressors SRC1, SRC2, and HDAC2 were downregulated. Hence, MED1 is a T3-dependent and -independent coactivator on the TSHβ gene promoter.

  9. "I am active": effects of a program to promote active aging.

    Science.gov (United States)

    Mendoza-Ruvalcaba, Neyda Ma; Arias-Merino, Elva Dolores

    2015-01-01

    Active aging involves a general lifestyle strategy that allows preservation of both physical and mental health during the aging process. "I am Active" is a program designed to promote active aging by increased physical activity, healthy nutritional habits, and cognitive functioning. The purpose of this study was to assess the effectiveness of this program. Sixty-four healthy adults aged 60 years or older were recruited from senior centers and randomly allocated to an experimental group (n=31) or a control group (n=33). Baseline, post-test, and 6-month follow-up assessments were performed after the theoretical-practical intervention. Effect sizes were calculated. At the conclusion of the program, the experimental group showed significant improvement compared with the control group in the following domains: physical activity (falls risk, balance, flexibility, self-efficacy), nutrition (self-efficacy and nutritional status), cognitive performance (processing speed and self-efficacy), and quality of life (general, health and functionality, social and economic status). Although some declines were reported, improvements at follow-up remained in self-efficacy for physical activity, self-efficacy for nutrition, and processing speed, and participants had better nutritional status and quality of life overall. Our findings show that this program promotes improvements in domains of active aging, mainly in self-efficacy beliefs as well as in quality of life in healthy elders.

  10. Load-related brain activation predicts spatial working memory performance in youth aged 9-12 and is associated with executive function at earlier ages.

    Science.gov (United States)

    Huang, Anna S; Klein, Daniel N; Leung, Hoi-Chung

    2016-02-01

    Spatial working memory is a central cognitive process that matures through adolescence in conjunction with major changes in brain function and anatomy. Here we focused on late childhood and early adolescence to more closely examine the neural correlates of performance variability during this important transition period. Using a modified spatial 1-back task with two memory load conditions in an fMRI study, we examined the relationship between load-dependent neural responses and task performance in a sample of 39 youth aged 9-12 years. Our data revealed that between-subject differences in task performance was predicted by load-dependent deactivation in default network regions, including the ventral anterior cingulate cortex (vACC) and posterior cingulate cortex (PCC). Although load-dependent increases in activation in prefrontal and posterior parietal regions were only weakly correlated with performance, increased prefrontal-parietal coupling was associated with better performance. Furthermore, behavioral measures of executive function from as early as age 3 predicted current load-dependent deactivation in vACC and PCC. These findings suggest that both task positive and task negative brain activation during spatial working memory contributed to successful task performance in late childhood/early adolescence. This may serve as a good model for studying executive control deficits in developmental disorders. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Impulsive traits and 5-HT2A receptor promoter polymorphism in alcohol dependents: possible association but no influence of personality disorders.

    Science.gov (United States)

    Preuss, U W; Koller, G; Bondy, B; Bahlmann, M; Soyka, M

    2001-01-01

    Impulsive behavior in alcoholics puts them at serious risk of severer course of disease and has been related to the serotonergic neurotransmission dysfunction. The aim of this study is to investigate the association between impulsive aggression in alcohol dependents with regard to the G-1438A polymorphism in the promoter region of the 5-HT2A receptor gene. Furthermore, we investigated the statistical interaction between 5-HT2A alleles, antisocial personality disorder (APD) and impulsive aggression in alcohol dependents. Alcohol dependents were investigated because these personality disorders and impulsive behavior are very frequent in alcohol dependence anf of clinical relevance. One hundred and thirty-five patients of German descent meeting DSM-IV criteria of alcohol dependence were recruited. Blood samples were taken from alcohol dependents to determine 5-HT2A promoter polymorphisms using PCR (polymerase chain reaction) of lymphocyte DNA. Impulsive aggression was assessed using a German version of the Barratt Impulsiveness Scale which was translated and backtranslated. Alcohol dependents were subdivided into low- or high-impulsivity groups using a median split of the Barratt score. APD and borderline personality disorder (BPD) were assessed using the SCID-II interview. The low-impulsivity group was slightly older and showed a later age at alcoholism onset than the highly impulsive group. Alcohol dependents with high impulsive traits showed a significant association with 5-HT2A 1438 A alleles. After excluding alcohol dependents with APD or BPD from the analysis, this association remained significant. Furthermore, no association between APD, BPD and 5-HT2A alleles was noted. Inpatient alcohol dependents showed a significant association between 5-HT2A A alleles and impulsive traits, independent of the presence of APD or BPD. No association was noted between personality disorders and the polymorphism. This is the first report about an association of 5-HT2A promoter

  12. Obesity increases the risk of renal involvement in children with Henoch-Schönlein purpura.

    Science.gov (United States)

    Zhao, Yong-Li; Liu, Zheng-Juan; Bai, Xue-Mei; Wang, Yu-Chuan; Li, Guo-Hua; Yan, Xue-Yan

    2015-10-01

    The main aim of this study was to evaluate the relationship between obesity and renal involvement in children with Henoch-Schönlein purpura (HSP). A retrospective study of 141 pediatric patients with HSP was conducted in our hospital. The clinical data of all patients were collected from the electronic medical record management system from January 2010 to June 2014. The possible risk factors of renal involvement, especially obesity, were analyzed using univariate and multivariate analyses. Renal involvement occurred in 45/141 of the patients. A univariate analysis showed that an age more than 7 years at onset, persistent purpura, obesity, time from symptoms onset to diagnosis more than 14 days, and decreased C3 all increased the risk of renal involvement in HSP. The forward stepwise logistic regression analysis indicated obesity (odds ratio (OR) 4.43, 95 % confidence interval (CI) 1.896 to 10.358), age more than 7 years at onset (OR 2.81, 95 % CI 1.142 to 6.907), and persistent purpura (OR 2.57, 95 % CI 1.119 to 5.909) were independent risk factors for renal involvement. Our results show that obesity can increase the hazard of renal involvement in children with HSP and reconfirm that older age at onset and persistent purpura are the independent risk factors for renal involvement. • There have been some reports that obesity was associated with the development of renal injury. • It is not clear whether obesity can increase the risk of renal involvement in children with HSP. What is New: • The main finding of this study is that obesity can increase the hazard of renal involvement in children with HSP.

  13. Cranberry interacts with dietary macronutrients to promote healthy aging in Drosophila.

    Science.gov (United States)

    Wang, Cecilia; Yolitz, Jason; Alberico, Thomas; Laslo, Mara; Sun, Yaning; Wheeler, Charles T; Sun, Xiaoping; Zou, Sige

    2014-08-01

    Botanicals possess numerous bioactivities, and some promote healthy aging. Dietary macronutrients are major determinants of life span. The interaction between botanicals and macronutrients that modulates life span is not well understood. Here, we investigated the effect of a cranberry-containing botanical on life span and the influence of macronutrients on the longevity-related effect of cranberry in Drosophila. Flies were supplemented with cranberry on three dietary conditions: standard, high sugar-low protein, and low sugar-high protein diets. We found that cranberry slightly extended life span in males fed with the low sugar-high protein diet but not with other diets. Cranberry extended life span in females fed with the standard diet and more prominently the high sugar-low protein diet but not with the low sugar-high protein diet. Life-span extension was associated with increased reproduction and higher expression of oxidative stress and heat shock response genes. Moreover, cranberry improved survival of sod1 knockdown and dfoxo mutant flies but did not increase wild-type fly's resistance to acute oxidative stress. Cranberry slightly extended life span in flies fed with a high-fat diet. These findings suggest that cranberry promotes healthy aging by increasing stress responsiveness. Our study reveals an interaction of cranberry with dietary macronutrients and stresses the importance of considering diet composition in designing interventions for promoting healthy aging. Published by Oxford University Press on behalf of the Gerontological Society of America 2013.

  14. CDC Vital Signs-Heart Age

    Centers for Disease Control (CDC) Podcasts

    2015-09-01

    This podcast is based on the September 2015 CDC Vital Signs report. Your heart age is the age of your heart and blood vessels as a result of your risk factors for heart attack and stroke. If you smoke or have high blood pressure, your heart age will be much higher than your actual age. Learn what you can do to lower your heart age and keep it low.  Created: 9/1/2015 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 9/1/2015.

  15. Annette Geiger (Hg.: Der schöne Körper. Köln u.a.: Böhlau Verlag 2008

    Directory of Open Access Journals (Sweden)

    Susanne Gramatzki

    2009-07-01

    Full Text Available In den Beiträgen des Bandes werden unterschiedlichste Formen des Schönheitshandelns in Vergangenheit und Gegenwart unter einer kulturwissenschaftlichen Perspektive beleuchtet. Modische Kleidung, dekorative Kosmetik, Diäten, Figurtraining, Schönheitsoperationen usw. stehen dem Ich als Techniken zur Verfügung, um einem idealen, häufig über die Medien vermittelten Körperbild nahezukommen. Der instruktive und angemessen bebilderte Band betrachtet diese Körperpraktiken als gleichermaßen gesellschaftliche wie ästhetische Phänomene; Zwang und Lust der Simulation werden von den Autor/-innen ebenso behandelt wie das Verhältnis von (Geschlechter-Identität und (Geschlechter-Performanz.The essays in this volume illuminate the most diverse forms of past and present acts of beauty from the perspective of Cultural Studies. Fashionable clothing, decorative cosmetics, diets, body sculpting, cosmetic operations, etc. are available to the individual as techniques to achieve the ideal body image that is often communicated through the media. The instructive and appropriately illustrated volume sees these body practices as both social and aesthetic phenomena. The authors address compulsion, the desire for simulation, and the relationship between (gender identity and (gender performance.

  16. Melatonin prevents postovulatory oocyte aging and promotes subsequent embryonic development in the pig.

    Science.gov (United States)

    Wang, Tao; Gao, Ying-Ying; Chen, Li; Nie, Zheng-Wen; Cheng, Wei; Liu, Xiaoyan; Schatten, Heide; Zhang, Xia; Miao, Yi-Liang

    2017-06-26

    Oxidative stress is known as a major contributing factor involved in oocyte aging, which negatively affects oocyte quality and development after fertilization. Melatonin is an effective free radical scavenger and its metabolites AFMK and AMK are powerful detoxifiers that eliminate free radicals. In this study, we used porcine oocytes to test the hypothesis that melatonin could scavenge free radicals produced during oocyte aging, thereby maintaining oocyte quality. We compared reactive oxygen species levels, apoptosis levels, mitochondrial membrane potential ratios, total glutathione contents and expression levels in fresh, aged and melatonin-treated aged porcine oocytes and observed the percentage of blastocyst formation following parthenogenetic activation. We found that melatonin could effectively maintain the morphology of oocytes observed in control oocytes, alleviate oxidative stress, markedly decrease early apoptosis levels, retard the decline of mitochondrial membrane potential and significantly promote subsequent embryonic development in oocytes aged for 24 hr in vitro . These results strongly suggest that melatonin can prevent postovulatory oocyte aging and promote subsequent embryonic development in the pig, which might find practical applications to control oocyte aging in other mammalian species including humans to maintain the quality of human oocytes when performing clinical assisted reproductive technology.

  17. Molecular and cellular mechanisms of the age-dependency of opioid analgesia and tolerance

    Directory of Open Access Journals (Sweden)

    Zhao Jing

    2012-05-01

    Full Text Available Abstract The age-dependency of opioid analgesia and tolerance has been noticed in both clinical observation and laboratory studies. Evidence shows that many molecular and cellular events that play essential roles in opioid analgesia and tolerance are actually age-dependent. For example, the expression and functions of endogenous opioid peptides, multiple types of opioid receptors, G protein subunits that couple to opioid receptors, and regulators of G protein signaling (RGS proteins change with development and age. Other signaling systems that are critical to opioid tolerance development, such as N-methyl-D-aspartic acid (NMDA receptors, also undergo age-related changes. It is plausible that the age-dependent expression and functions of molecules within and related to the opioid signaling pathways, as well as age-dependent cellular activity such as agonist-induced opioid receptor internalization and desensitization, eventually lead to significant age-dependent changes in opioid analgesia and tolerance development.

  18. G9a coordinates with the RPA complex to promote DNA damage repair and cell survival.

    Science.gov (United States)

    Yang, Qiaoyan; Zhu, Qian; Lu, Xiaopeng; Du, Yipeng; Cao, Linlin; Shen, Changchun; Hou, Tianyun; Li, Meiting; Li, Zhiming; Liu, Chaohua; Wu, Di; Xu, Xingzhi; Wang, Lina; Wang, Haiying; Zhao, Ying; Yang, Yang; Zhu, Wei-Guo

    2017-07-25

    Histone methyltransferase G9a has critical roles in promoting cancer-cell growth and gene suppression, but whether it is also associated with the DNA damage response is rarely studied. Here, we report that loss of G9a impairs DNA damage repair and enhances the sensitivity of cancer cells to radiation and chemotherapeutics. In response to DNA double-strand breaks (DSBs), G9a is phosphorylated at serine 211 by casein kinase 2 (CK2) and recruited to chromatin. The chromatin-enriched G9a can then directly interact with replication protein A (RPA) and promote loading of the RPA and Rad51 recombinase to DSBs. This mechanism facilitates homologous recombination (HR) and cell survival. We confirmed the interaction between RPA and G9a to be critical for RPA foci formation and HR upon DNA damage. Collectively, our findings demonstrate a regulatory pathway based on CK2-G9a-RPA that permits HR in cancer cells and provide further rationale for the use of G9a inhibitors as a cancer therapeutic.

  19. Complete genome sequence of the rapeseed plant-growth promoting Serratia plymuthica strain AS9

    Energy Technology Data Exchange (ETDEWEB)

    Neupane, Saraswoti [Uppsala University, Uppsala, Sweden; Hogberg, Nils [Uppsala University, Uppsala, Sweden; Alstrom, Sadhna [Uppsala University, Uppsala, Sweden; Lucas, Susan [U.S. Department of Energy, Joint Genome Institute; Han, James [U.S. Department of Energy, Joint Genome Institute; Lapidus, Alla L. [U.S. Department of Energy, Joint Genome Institute; Cheng, Jan-Fang [U.S. Department of Energy, Joint Genome Institute; Bruce, David [Los Alamos National Laboratory (LANL); Goodwin, Lynne A. [Los Alamos National Laboratory (LANL); Pitluck, Sam [U.S. Department of Energy, Joint Genome Institute; Peters, Lin [U.S. Department of Energy, Joint Genome Institute; Ovchinnikova, Galina [U.S. Department of Energy, Joint Genome Institute; Lu, Megan [Los Alamos National Laboratory (LANL); Han, Cliff [Los Alamos National Laboratory (LANL); Detter, J. Chris [U.S. Department of Energy, Joint Genome Institute; Tapia, Roxanne [Los Alamos National Laboratory (LANL); Fiebig, Anne [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Land, Miriam L [ORNL; Hauser, Loren John [ORNL; Kyrpides, Nikos C [U.S. Department of Energy, Joint Genome Institute; Ivanova, N [U.S. Department of Energy, Joint Genome Institute; Pagani, Ioanna [U.S. Department of Energy, Joint Genome Institute; Klenk, Hans-Peter [DSMZ - German Collection of Microorganisms and Cell Cultures GmbH, Braunschweig, Germany; Woyke, Tanja [U.S. Department of Energy, Joint Genome Institute; Finlay, Roger D. [Uppsala University, Uppsala, Sweden

    2012-01-01

    Serratia plymuthica are plant-associated, plant beneficial species belonging to the family Enterobacteriaceae. The members of the genus Serratia are ubiquitous in nature and their life style varies from endophytic to free-living. S. plymuthica AS9 is of special interest for its ability to inhibit fungal pathogens of rapeseed and to promote plant growth. The genome of S. plymuthica AS9 comprises a 5,442,880 bp long circular chromosome that consists of 4,952 protein-coding genes, 87 tRNA genes and 7 rRNA operons. This genome is part of the project entitled Genomics of four rapeseed plant growth promoting bacteria with antagonistic effect on plant pathogens awarded through the 2010 DOE-JGI Community Sequencing Program (CSP2010).

  20. Circadian rhythms on skin function of hairless rats: light and thermic influences.

    Science.gov (United States)

    Flo, Ana; Díez-Noguera, Antoni; Calpena, Ana C; Cambras, Trinitat

    2014-03-01

    Circadian rhythms are present in most functions of living beings. We have demonstrated the presence of circadian rhythms in skin variables (transepidermal water loss, TEWL; stratum corneum hydration, SCH; and skin temperature) in hairless rats under different environmental conditions of light and temperature. Circadian rhythms in TEWL and SCH showed mean amplitudes of about 20% and 14% around the mean, respectively, and appeared under light-dark cycles as well as under constant darkness. Environmental temperature was able to override TEWL, but not SCH rhythm, evidencing the dependency of TEWL on the temperature. Mean daily values of TEWL and SCH, and also the amplitude of TEWL rhythm, increased with the age of the animal. Under constant light, situation that induces arrhythmicity in rats, SCH and TEWL were inversely correlated. The results suggest the importance to take into account the functional skin rhythms in research in dermatological sciences. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Toscana virus NSs protein promotes degradation of double-stranded RNA-dependent protein kinase.

    Science.gov (United States)

    Kalveram, Birte; Ikegami, Tetsuro

    2013-04-01

    Toscana virus (TOSV), which is transmitted by Phlebotomus spp. sandflies, is a major etiologic agent of aseptic meningitis and encephalitis in the Mediterranean. Like other members of the genus Phlebovirus of the family Bunyaviridae, TOSV encodes a nonstructural protein (NSs) in its small RNA segment. Although the NSs of Rift Valley fever virus (RVFV) has been identified as an important virulence factor, which suppresses host general transcription, inhibits transcription from the beta interferon promoter, and promotes the proteasomal degradation of double-stranded RNA-dependent protein kinase (PKR), little is known about the functions of NSs proteins encoded by less-pathogenic members of this genus. In this study we report that TOSV is able to downregulate PKR with similar efficiency as RVFV, while infection with the other phleboviruses-i.e., Punta Toro virus, sandfly fever Sicilian virus, or Frijoles virus-has no effect on cellular PKR levels. In contrast to RVFV, however, cellular transcription remains unaffected during TOSV infection. TOSV NSs protein promotes the proteasome-dependent downregulation of PKR and is able to interact with kinase-inactive PKR in infected cells.

  2. Age-dependent tissue-specific exposure of cell phone users

    Energy Technology Data Exchange (ETDEWEB)

    Christ, Andreas; Gosselin, Marie-Christine; Kuehn, Sven; Kuster, Niels [Foundation for Research on Information Technologies in Society (IT' IS), Zeughausstr. 43, 8004 Zuerich (Switzerland); Christopoulou, Maria [National Technical University of Athens, School of Electrical and Computer Engineering, 9 Iroon Polytechniou Str., 15780 Athens (Greece)], E-mail: christ@itis.ethz.ch

    2010-04-07

    The peak spatial specific absorption rate (SAR) assessed with the standardized specific anthropometric mannequin head phantom has been shown to yield a conservative exposure estimate for both adults and children using mobile phones. There are, however, questions remaining concerning the impact of age-dependent dielectric tissue properties and age-dependent proportions of the skull, face and ear on the global and local absorption, in particular in the brain tissues. In this study, we compare the absorption in various parts of the cortex for different magnetic resonance imaging-based head phantoms of adults and children exposed to different models of mobile phones. The results show that the locally induced fields in children can be significantly higher (>3 dB) in subregions of the brain (cortex, hippocampus and hypothalamus) and the eye due to the closer proximity of the phone to these tissues. The increase is even larger for bone marrow (>10 dB) as a result of its significantly high conductivity. Tissues such as the pineal gland show no increase since their distances to the phone are not a function of age. This study, however, confirms previous findings saying that there are no age-dependent changes of the peak spatial SAR when averaged over the entire head.

  3. Age-dependent tissue-specific exposure of cell phone users

    International Nuclear Information System (INIS)

    Christ, Andreas; Gosselin, Marie-Christine; Kuehn, Sven; Kuster, Niels; Christopoulou, Maria

    2010-01-01

    The peak spatial specific absorption rate (SAR) assessed with the standardized specific anthropometric mannequin head phantom has been shown to yield a conservative exposure estimate for both adults and children using mobile phones. There are, however, questions remaining concerning the impact of age-dependent dielectric tissue properties and age-dependent proportions of the skull, face and ear on the global and local absorption, in particular in the brain tissues. In this study, we compare the absorption in various parts of the cortex for different magnetic resonance imaging-based head phantoms of adults and children exposed to different models of mobile phones. The results show that the locally induced fields in children can be significantly higher (>3 dB) in subregions of the brain (cortex, hippocampus and hypothalamus) and the eye due to the closer proximity of the phone to these tissues. The increase is even larger for bone marrow (>10 dB) as a result of its significantly high conductivity. Tissues such as the pineal gland show no increase since their distances to the phone are not a function of age. This study, however, confirms previous findings saying that there are no age-dependent changes of the peak spatial SAR when averaged over the entire head.

  4. Age-Dependent Mesial Temporal Lobe Lateralization in Language FMRI

    Science.gov (United States)

    Sepeta, Leigh N.; Berl, Madison M.; Wilke, Marko; You, Xiaozhen; Mehta, Meera; Xu, Benjamin; Inati, Sara; Dustin, Irene; Khan, Omar; Austermuehle, Alison; Theodore, William H.; Gaillard, William D.

    2015-01-01

    Objective FMRI activation of the mesial temporal lobe (MTL) may be important for epilepsy surgical planning. We examined MTL activation and lateralization during language fMRI in children and adults with focal epilepsy. Methods 142 controls and patients with left hemisphere focal epilepsy (Pediatric: epilepsy, n = 17, mean age = 9.9 ± 2.0; controls, n = 48; mean age = 9.1 ± 2.6; Adult: epilepsy, n = 20, mean age = 26.7 ± 5.8; controls, n = 57, mean age = 26.2 ± 7.5) underwent 3T fMRI using a language task (auditory description decision task). Image processing and analyses were conducted in SPM8; ROIs included MTL, Broca’s area, and Wernicke’s area. We assessed group and individual MTL activation, and examined degree of lateralization. Results Patients and controls (pediatric and adult) demonstrated group and individual MTL activation during language fMRI. MTL activation was left lateralized for adults but less so in children (p’s < 0.005). Patients did not differ from controls in either age group. Stronger left-lateralized MTL activation was related to older age (p = 0.02). Language lateralization (Broca’s and Wernicke’s) predicted 19% of the variance in MTL lateralization for adults (p = 0.001), but not children. Significance Language fMRI may be used to elicit group and individual MTL activation. The developmental difference in MTL lateralization and its association with language lateralization suggests a developmental shift in lateralization of MTL function, with increased left lateralization across the age span. This shift may help explain why children have better memory outcomes following resection compared to adults. PMID:26696589

  5. Potential factors that may promote successful cognitive aging

    Directory of Open Access Journals (Sweden)

    Vance DE

    2012-06-01

    Full Text Available David E VanceCenter for Nursing Research, School of Nursing, Edward R Roybal Center for Translational Research in Aging and Mobility, University of Alabama at Birmingham (UAB, Birmingham, AL, USAAbstract: With the unprecedented number of older adults worldwide, it is important to consider ways of facilitating successful cognitive aging. One way to think of this is by augmenting or bolstering cognitive reserve. Loosely defined, cognitive reserve is considered a neurological reservoir that can be depleted by physiological insults (eg, white matter hyperintensities, oxidative stress to the brain but yet maintain optimal cognitive functioning. Cognitive reserve is built up or depleted by processes of positive and negative neuroplasticity, respectively. Lifestyle factors such as physical exercise (+, mental stimulation (+, good sleep hygiene (+, substance abuse (-, sedentary lifestyle (-, chronic stress and depression (-, social isolation (-, and poor health (- can either promote or discourage positive and negative neuroplasticity, which in turn impacts cognitive reserve. Nurses are encouraged to understand these processes so they can help facilitate successful cognitive aging in their patients.Keywords: cognitive reserve, Alzheimer's disease, neuroplasticity

  6. S100A9 interaction with TLR4 promotes tumor growth.

    Directory of Open Access Journals (Sweden)

    Eva Källberg

    Full Text Available By breeding TRAMP mice with S100A9 knock-out (S100A9(-/- animals and scoring the appearance of palpable tumors we observed a delayed tumor growth in animals devoid of S100A9 expression. CD11b(+ S100A9 expressing cells were not observed in normal prostate tissue from control C57BL/6 mice but were readily detected in TRAMP prostate tumors. Also, S100A9 expression was observed in association with CD68(+ macrophages in biopsies from human prostate tumors. Delayed growth of TRAMP tumors was also observed in mice lacking the S100A9 ligand TLR4. In the EL-4 lymphoma model tumor growth inhibition was observed in S100A9(-/- and TLR4(-/-, but not in RAGE(-/- animals lacking an alternative S100A9 receptor. When expression of immune-regulating genes was analyzed using RT-PCR the only common change observed in mice lacking S100A9 and TLR4 was a down-regulation of TGFβ expression in splenic CD11b(+ cells. Lastly, treatment of mice with a small molecule (ABR-215050 that inhibits S100A9 binding to TLR4 inhibited EL4 tumor growth. Thus, S100A9 and TLR4 appear to be involved in promoting tumor growth in two different tumor models and pharmacological inhibition of S100A9-TLR4 interactions is a novel and promising target for anti-tumor therapies.

  7. S100A9 Interaction with TLR4 Promotes Tumor Growth

    Science.gov (United States)

    Källberg, Eva; Vogl, Thomas; Liberg, David; Olsson, Anders; Björk, Per; Wikström, Pernilla; Bergh, Anders; Roth, Johannes; Ivars, Fredrik; Leanderson, Tomas

    2012-01-01

    By breeding TRAMP mice with S100A9 knock-out (S100A9−/−) animals and scoring the appearance of palpable tumors we observed a delayed tumor growth in animals devoid of S100A9 expression. CD11b+ S100A9 expressing cells were not observed in normal prostate tissue from control C57BL/6 mice but were readily detected in TRAMP prostate tumors. Also, S100A9 expression was observed in association with CD68+ macrophages in biopsies from human prostate tumors. Delayed growth of TRAMP tumors was also observed in mice lacking the S100A9 ligand TLR4. In the EL-4 lymphoma model tumor growth inhibition was observed in S100A9−/− and TLR4−/−, but not in RAGE−/− animals lacking an alternative S100A9 receptor. When expression of immune-regulating genes was analyzed using RT-PCR the only common change observed in mice lacking S100A9 and TLR4 was a down-regulation of TGFβ expression in splenic CD11b+ cells. Lastly, treatment of mice with a small molecule (ABR-215050) that inhibits S100A9 binding to TLR4 inhibited EL4 tumor growth. Thus, S100A9 and TLR4 appear to be involved in promoting tumor growth in two different tumor models and pharmacological inhibition of S100A9-TLR4 interactions is a novel and promising target for anti-tumor therapies. PMID:22470535

  8. Aging-dependent reduction in glyoxalase 1 delays wound healing.

    Science.gov (United States)

    Fleming, Thomas H; Theilen, Till-Martin; Masania, Jinit; Wunderle, Marius; Karimi, Jamshid; Vittas, Spiros; Bernauer, Rainer; Bierhaus, Angelika; Rabbani, Naila; Thornalley, Paul J; Kroll, Jens; Tyedmers, Jens; Nawrotzki, Ralph; Herzig, Stephan; Brownlee, Michael; Nawroth, Peter P

    2013-01-01

    Methylglyoxal (MG), the major dicarbonyl substrate of the enzyme glyoxalase 1 (GLO1), is a reactive metabolite formed via glycolytic flux. Decreased GLO1 activity in situ has been shown to result in an accumulation of MG and increased formation of advanced glycation endproducts, both of which can accumulate during physiological aging and at an accelerated rate in diabetes and other chronic degenerative diseases. To determine the physiological consequences which result from elevated MG levels and the role of MG and GLO1 in aging, wound healing in young (≤12 weeks) and old (≥52 weeks) wild-type mice was studied. Old mice were found to have a significantly slower rate of wound healing compared to young mice (74.9 ± 2.2 vs. 55.4 ± 1.5% wound closure at day 6; 26% decrease; p wounds of young mice, decreased wound healing by 24% compared to untreated mice, whereas application of BSA modified minimally by MG had no effect. Treatment of either young or old mice with aminoguanidine, a scavenger of free MG, significantly increased wound closure by 16% (66.8 ± 1.6 vs. 77.2 ± 3.1%; p wound healing in the old mice was restored to the level observed in the young mice. These findings were confirmed in vitro, as MG reduced migration and proliferation of fibroblasts derived from young and old, wild-type mice. The data demonstrate that the balance between MG and age-dependent GLO1 downregulation contributes to delayed wound healing in old mice. Copyright © 2013 S. Karger AG, Basel.

  9. Insufficient DNA methylation affects healthy aging and promotes age-related health problems.

    Science.gov (United States)

    Liu, Liang; van Groen, Thomas; Kadish, Inga; Li, Yuanyuan; Wang, Deli; James, Smitha R; Karpf, Adam R; Tollefsbol, Trygve O

    2011-08-01

    DNA methylation plays an integral role in development and aging through epigenetic regulation of genome function. DNA methyltransferase 1 (Dnmt1) is the most prevalent DNA methyltransferase that maintains genomic methylation stability. To further elucidate the function of Dnmt1 in aging and age-related diseases, we exploited the Dnmt1+/- mouse model to investigate how Dnmt1 haploinsufficiency impacts the aging process by assessing the changes of several major aging phenotypes. We confirmed that Dnmt1 haploinsufficiency indeed decreases DNA methylation as a result of reduced Dnmt1 expression. To assess the effect of Dnmt1 haploinsufficiency on general body composition, we performed dual-energy X-ray absorptiometry analysis and showed that reduced Dnmt1 activity decreased bone mineral density and body weight, but with no significant impact on mortality or body fat content. Using behavioral tests, we demonstrated that Dnmt1 haploinsufficiency impairs learning and memory functions in an age-dependent manner. Taken together, our findings point to the interesting likelihood that reduced genomic methylation activity adversely affects the healthy aging process without altering survival and mortality. Our studies demonstrated that cognitive functions of the central nervous system are modulated by Dnmt1 activity and genomic methylation, highlighting the significance of the original epigenetic hypothesis underlying memory coding and function.

  10. An age dependent model for radium metabolism in man.

    Science.gov (United States)

    Johnson, J R

    1983-01-01

    The model developed by a Task Group of Committee 2 of ICRP to describe Alkaline Earth Metabolism in Adult Man (ICRP Publication 20) has been modified so that recycling is handled explicitly, and retention in mineral bone is represented by second compartments rather than by the product of a power function and an exponential. This model has been extended to include all ages from birth to adult man, and has been coupled with modified "ICRP" lung and G.I. tract models so that activity in organs can be calculated as functions of time during or after exposures. These activities, and age dependent "specific effective energy" factors, are then used to calculate age dependent dose rates, and dose commitments. This presentation describes this work, with emphasis on the model parameters and results obtained for radium.

  11. #WaysToRelax: developing an online alcohol-related health promotion animation for people aged 55 and older.

    Science.gov (United States)

    Ferguson, Nyssa; Savic, Michael; Manning, Victoria; Lubman, Daniel

    2017-04-27

    Alcohol use among middle-aged and older adults (55 years and older) is increasingly becoming a public health concern. Despite this, there is relatively little research on the experiences of alcohol use and related concerns among people aged 55 and older to inform tailored and engaging health promotion activities. To address this gap, we aimed to develop an engaging alcohol-related health promotion resource for people aged 55 and older. We drew on a research-into-action approach, which involved: 1) thematic analysis of alcohol-related concerns in online counselling transcripts of 70 people aged 55 and older, 2) a review of health promotion literature, and 3) consultation with consumers of alcohol and other drug services, and carers. The research phase highlighted that people aged 55 and older were concerned that their reliance on alcohol use to manage stress had become a habit they wanted to shift. Alongside this, the literature showed that people aged 55 and older were often dismissive of conventional health promotion activities, and pointed to the benefits of conveying health promotion messages through animation. In response, we developed an animation to stimulate reflection and thought about other ways to relax and manage stress. We drew on health promotion principles to ensure that the animation had a positive message and was engaging without being ageist or paternalistic. It was further refined with input from consumers and carers, who thought the animation was appropriate, appealing and useful. Future activities will include further dissemination and evaluation of the animation and associated activities.

  12. #WaysToRelax: developing an online alcohol-related health promotion animation for people aged 55 and older

    Directory of Open Access Journals (Sweden)

    Nyssa Ferguson

    2017-04-01

    Full Text Available Alcohol use among middle-aged and older adults (55 years and older is increasingly becoming a public health concern. Despite this, there is relatively little research on the experiences of alcohol use and related concerns among people aged 55 and older to inform tailored and engaging health promotion activities. To address this gap, we aimed to develop an engaging alcohol-related health promotion resource for people aged 55 and older. We drew on a research-into-action approach, which involved: 1 thematic analysis of alcohol-related concerns in online counselling transcripts of 70 people aged 55 and older, 2 a review of health promotion literature, and 3 consultation with consumers of alcohol and other drug services, and carers. The research phase highlighted that people aged 55 and older were concerned that their reliance on alcohol use to manage stress had become a habit they wanted to shift. Alongside this, the literature showed that people aged 55 and older were often dismissive of conventional health promotion activities, and pointed to the benefits of conveying health promotion messages through animation. In response, we developed an animation to stimulate reflection and thought about other ways to relax and manage stress. We drew on health promotion principles to ensure that the animation had a positive message and was engaging without being ageist or paternalistic. It was further refined with input from consumers and carers, who thought the animation was appropriate, appealing and useful. Future activities will include further dissemination and evaluation of the animation and associated activities.

  13. Effect of the dopamine D1-like receptor antagonist SCH 23390 on the microstructure of ingestive behaviour in water-deprived rats licking for water and NaCl solutions.

    Science.gov (United States)

    Galistu, Adriana; D'Aquila, Paolo S

    2012-01-18

    The analysis of licking microstructure provides measures, size and number of licking bouts, which might reveal, respectively, reward evaluation and behavioural activation. Based on the different effects of the dopamine D1-like and D2-like receptor antagonists SCH 23390 and raclopride on licking for sucrose, in particular the failure of the former to reduce bout size and the ability of the latter to induce a within-session decrement of bout number resembling either reward devaluation or neuroleptics on instrumental responding, we suggested that activation of reward-associated responses depends on dopamine D1-like receptor stimulation, and its level is updated on the basis of a dopamine D2-like receptor-mediated reward evaluation. Consistent results were obtained in a study examining the effect of dopamine D2-like receptor antagonism in rats licking for NaCl solutions and water. In this study, we examined the effects of the dopamine D1-like receptor antagonist SCH 23390 (0, 10, 20 and 40 μg/kg) on the microstructure of licking for water and sodium chloride solutions (0.075 M, 0.15 M, 0.3 M) in 12 h water deprived rats. Rats were exposed to each solution for 60 s either after the first lick or after 3 min that the animals were placed in the chambers. Bout size, but not bout number, was decreased at the highest NaCl concentration. SCH 23390 produced a decrease of bout number and of lick number mainly due to the decreased number of subjects engaging in licking behaviour, and failed to reduce bout size for Na Cl and water at a dose which increased the latency to the 1st lick but did not affect the intra-bout lick rate. In agreement with previous observations, these results suggest that dopamine D1-like receptors play an important role in the activation of reward-oriented responses. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    KAUST Repository

    Pardo, Luba M.

    2013-02-19

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

  15. Delayed wound healing in aged skin rat models after thermal injury is associated with an increased MMP-9, K6 and CD44 expression.

    Science.gov (United States)

    Simonetti, Oriana; Oriana, Simonetti; Lucarini, Guendalina; Guendalina, Lucarini; Cirioni, Oscar; Oscar, Cirioni; Zizzi, Antonio; Antonio, Zizzi; Orlando, Fiorenza; Fiorenza, Orlando; Provinciali, Mauro; Mauro, Provinciali; Di Primio, Roberto; Roberto, Di Primio; Giacometti, Andrea; Andrea, Giacometti; Offidani, Annamaria; Annamaria, Offidani

    2013-06-01

    Age-related differences in wound healing have been documented but little is known about the wound healing mechanism after burns. Our aim was to compare histological features and immunohistochemical expression of matrix metalloproteinase-9 (MMP-9), collagen IV, K6 and CD44 in the burn wound healing process in aged and young rats. Following burns the appearance of the wound bed in aged rats had progressed but slowly, resulting in a delayed healing process compared to the young rats. At 21 days after injury, epithelial K6, MMP-9 and CD44 expression was significantly increased in aged rats with respect to young rats; moreover, in the aged rat group we observed a not fully reconstituted basement membrane. K6, MMP-9 and CD44 expression was significantly increased in wounded skin compared to unwounded skin both in young and aged rats. We hypothesise that delayed burn skin wound healing process in the aged rats may represent an age dependent response to injury where K6, MMP-9 and CD44 play a key role. It is therefore possible to suggest that these factors contribute to the delayed wound healing in aged skin and that modulation could lead to a better and faster recovery of skin damage in elderly. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

  16. Location of skin lesions in Henoch-Schönlein purpura and its association with significant renal involvement.

    Science.gov (United States)

    St John, Jessica; Vedak, Priyanka; Garza-Mayers, Anna Cristina; Hoang, Mai P; Nigwekar, Sagar U; Kroshinsky, Daniela

    2018-01-01

    Henoch-Schönlein purpura (HSP) is a small vessel IgA-predominant vasculitis. To describe adult patients with HSP and determine if the distribution of skin lesions (ie, purpura above the waist or purpura below the waist only), is a predictor of significant renal involvement at the time of the skin biopsy and the months following. A retrospective study on renal function from 72 adult patients with skin-biopsy proven HSP. Longitudinal renal data were analyzed after HSP diagnosis by using baseline renal function for comparison. Statistical analysis adjusted for sex, age, and baseline creatinine revealed a trend between HSP lesions only on the upper and lower extremities and long-term renal involvement (4.767, P = .067). Moreover, in another analysis adjusted for age and baseline creatinine, lesions located only on the upper and lower extremities significantly increased the odds of having long-term significant renal involvement (6.55, P = .049) in men. This retrospective study used patient information that was subject to selection bias. In patients with HSP, skin lesion distribution on the extremities might be predictive of significant long-term renal involvement and might be critical for risk stratification and development of personalized diagnostics and therapeutics. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  17. Evaluation of the Mental Healthiness Aging Initiative: community program to promote awareness about mental health and aging issues.

    Science.gov (United States)

    Zanjani, Faika; Kruger, Tina; Murray, Deborah

    2012-04-01

    The objective of this study is to evaluate the Mental Healthiness Aging Initiative, designed to promote community awareness and knowledge about mental health and aging issues. This study occurred during 2007-2009 in 67 of 120 counties in Kentucky. A rural region (11 counties) received the intervention, consisting of focus groups, Extension Agent training, and television-based social marketing campaign. Partial-intervention counties (29 counties) received only the television-based social marketing campaign. The control counties (27 counties) received no intervention activities. Results indicated that the intervention counties agreed more with being able to assist elder adults with a potential mental illness. Also, the intervention counties understood the risk of consuming alcohol and medications better, but had a poorer recognition of drinking problems in elder adults. These findings need to be considered within study limitations, such as measurement error, degree of intervention exposure, and regional differences across intervention groups. The study demonstrates that community interventions on mental health awareness and knowledge are feasible within majority rural regions, with Extension Agents being gatekeepers, for promoting positive messages about mental health and aging issues.

  18. Age-dependent increase in green autofluorescence of blood ...

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    Protective enzymes against oxidative ... School of Life Sciences, Jawaharlal Nehru University, New Delhi 110 067, India ... provide evidence for an age dependent increase in the GAF of blood erythrocytes that is accentuated by depletion of.

  19. Transplantation of autologous synovial mesenchymal stem cells promotes meniscus regeneration in aged primates.

    Science.gov (United States)

    Kondo, Shimpei; Muneta, Takeshi; Nakagawa, Yusuke; Koga, Hideyuki; Watanabe, Toshifumi; Tsuji, Kunikazu; Sotome, Shinichi; Okawa, Atsushi; Kiuchi, Shinji; Ono, Hideo; Mizuno, Mitsuru; Sekiya, Ichiro

    2017-06-01

    Transplantation of aggregates of synovial mesenchymal stem cells (MSCs) enhanced meniscus regeneration in rats. Anatomy and biological properties of the meniscus depend on animal species. To apply this technique clinically, it is valuable to investigate the use of animals genetically close to humans. We investigated whether transplantation of aggregates of autologous synovial MSCs promoted meniscal regeneration in aged primates. Chynomolgus primates between 12 and 13 years old were used. After the anterior halves of the medial menisci in both knees were removed, an average of 14 aggregates consisting of 250,000 synovial MSCs were transplanted onto the meniscus defect. No aggregates were transplanted to the opposite knee for the control. Meniscus and articular cartilage were analyzed macroscopically, histologically, and by MRI T1rho mapping at 8 (n = 3) and 16 weeks (n = 4). The medial meniscus was larger and the modified Pauli's histological score for the regenerated meniscus was better in the MSC group than in the control group in each primate at 8 and 16 weeks. Mankin's score for the medial femoral condyle cartilage was better in the MSC group than in the control group in all primates at 16 weeks. T1rho value for both the regenerated meniscus and adjacent articular cartilage in the MSC group was closer to the normal meniscus than in the control group in all primates at 16 weeks. Transplantation of aggregates of autologous synovial MSCs promoted meniscus regeneration and delayed progression of degeneration of articular cartilage in aged primates. This is the first report dealing with meniscus regeneration in primates. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1274-1282, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  20. The Influence of the Brain on Overpopulation, Ageing and Dependency.

    Science.gov (United States)

    Cape, Ronald D. T.

    1989-01-01

    With time, an increasing number in the world population is becoming old, and changes in the aging brain mean that a significant proportion of the aged are likely to be dependent on others. The devotion of resources to research into the aging brain could bring benefits far outweighing the investment. (Author/CW)

  1. Subclinical hypothyroidism is associated with increased risk for all-cause and cardiovascular mortality in adults.

    Science.gov (United States)

    Tseng, Fen-Yu; Lin, Wen-Yuan; Lin, Cheng-Chieh; Lee, Long-Teng; Li, Tsai-Chung; Sung, Pei-Kun; Huang, Kuo-Chin

    2012-08-21

    This study sought to evaluate the relationship between subclinical hypothyroidism (SCH) and all-cause and cardiovascular disease (CVD) mortality. SCH may increase the risks of hypercholesterolemia and atherosclerosis. The associations between SCH and all-cause or CVD mortality are uncertain, on the basis of the results of previous studies. A baseline cohort of 115,746 participants without a history of thyroid disease, ≥20 years of age, was recruited in Taiwan. SCH was defined as a serum thyroid-stimulating hormone (TSH) level of 5.0 to 19.96 mIU/l with normal total thyroxine concentrations. Euthyroidism was defined as a serum TSH level of 0.47 to 4.9 mIU/l. Cox proportional hazards regression analysis was used to estimate the relative risks (RRs) of death from all-cause and CVD for adults with SCH during a 10-year follow-up period. There were 3,669 deaths during the follow-up period; 680 deaths were due to CVD. Compared with subjects with euthyroidism, after adjustment for age, sex, body mass index, diabetes, hypertension, dyslipidemia, smoking, alcohol consumption, betel nut chewing, physical activity, income, and education level, the RRs (95% confidence interval) of deaths from all-cause and CVD among subjects with SCH were 1.30 (1.02 to 1.66), and 1.68 (1.02 to 2.76), respectively. Adult Taiwanese with SCH had an increased risk for all-cause mortality and CVD death. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  2. Prenatal Dexamethasone and Postnatal High-Fat Diet Decrease Interferon Gamma Production through an Age-Dependent Histone Modification in Male Sprague-Dawley Rats

    Science.gov (United States)

    Yu, Hong-Ren; Tain, You-Lin; Sheen, Jiunn-Ming; Tiao, Mao-Meng; Chen, Chih-Cheng; Kuo, Ho-Chang; Hung, Pi-Lien; Hsieh, Kai-Sheng; Huang, Li-Tung

    2016-01-01

    Overexposure to prenatal glucocorticoid (GC) disturbs hypothalamic-pituitary-adrenocortical axis-associated neuroendocrine metabolism and susceptibility to metabolic syndrome. A high-fat (HF) diet is a major environmental factor that can cause metabolic syndrome. We aimed to investigate whether prenatal GC plus a postnatal HF diet could alter immune programming in rat offspring. Pregnant Sprague-Dawley rats were given intraperitoneal injections of dexamethasone or saline at 14–21 days of gestation. Male offspring were then divided into four groups: vehicle, prenatal dexamethasone exposure, postnatal HF diet (VHF), and prenatal dexamethasone exposure plus a postnatal HF diet (DHF). The rats were sacrificed and adaptive immune function was evaluated. Compared to the vehicle, the DHF group had lower interferon gamma (IFN-γ) production by splenocytes at postnatal day 120. Decreases in H3K9 acetylation and H3K36me3 levels at the IFN-γ promoter correlated with decreased IFN-γ production. The impaired IFN-γ production and aberrant site-specific histone modification at the IFN-γ promoter by prenatal dexamethasone treatment plus a postnatal HF diet resulted in resilience at postnatal day 180. Prenatal dexamethasone and a postnatal HF diet decreased IFN-γ production through a site-specific and an age-dependent histone modification. These findings suggest a mechanism by which prenatal exposure to GC and a postnatal environment exert effects on fetal immunity programming. PMID:27669212

  3. Prenatal Dexamethasone and Postnatal High-Fat Diet Decrease Interferon Gamma Production through an Age-Dependent Histone Modification in Male Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Hong-Ren Yu

    2016-09-01

    Full Text Available Overexposure to prenatal glucocorticoid (GC disturbs hypothalamic-pituitary-adrenocortical axis-associated neuroendocrine metabolism and susceptibility to metabolic syndrome. A high-fat (HF diet is a major environmental factor that can cause metabolic syndrome. We aimed to investigate whether prenatal GC plus a postnatal HF diet could alter immune programming in rat offspring. Pregnant Sprague-Dawley rats were given intraperitoneal injections of dexamethasone or saline at 14–21 days of gestation. Male offspring were then divided into four groups: vehicle, prenatal dexamethasone exposure, postnatal HF diet (VHF, and prenatal dexamethasone exposure plus a postnatal HF diet (DHF. The rats were sacrificed and adaptive immune function was evaluated. Compared to the vehicle, the DHF group had lower interferon gamma (IFN-γ production by splenocytes at postnatal day 120. Decreases in H3K9 acetylation and H3K36me3 levels at the IFN-γ promoter correlated with decreased IFN-γ production. The impaired IFN-γ production and aberrant site-specific histone modification at the IFN-γ promoter by prenatal dexamethasone treatment plus a postnatal HF diet resulted in resilience at postnatal day 180. Prenatal dexamethasone and a postnatal HF diet decreased IFN-γ production through a site-specific and an age-dependent histone modification. These findings suggest a mechanism by which prenatal exposure to GC and a postnatal environment exert effects on fetal immunity programming.

  4. Mutant alpha-synuclein causes age-dependent neuropathology in monkey brain.

    Science.gov (United States)

    Yang, Weili; Wang, Guohao; Wang, Chuan-En; Guo, Xiangyu; Yin, Peng; Gao, Jinquan; Tu, Zhuchi; Wang, Zhengbo; Wu, Jing; Hu, Xintian; Li, Shihua; Li, Xiao-Jiang

    2015-05-27

    Parkinson's disease (PD) is an age-dependent neurodegenerative disease that often occurs in those over age 60. Although rodents and small animals have been used widely to model PD and investigate its pathology, their short life span makes it difficult to assess the aging-related pathology that is likely to occur in PD patient brains. Here, we used brain tissues from rhesus monkeys at 2-3, 7-8, and >15 years of age to examine the expression of Parkin, PINK1, and α-synuclein, which are known to cause PD via loss- or gain-of-function mechanisms. We found that α-synuclein is increased in the older monkey brains, whereas Parkin and PINK1 are decreased or remain unchanged. Because of the gain of toxicity of α-synuclein, we performed stereotaxic injection of lentiviral vectors expressing mutant α-synuclein (A53T) into the substantia nigra of monkeys and found that aging also increases the accumulation of A53T in neurites and its associated neuropathology. A53T also causes more extensive reactive astrocytes and axonal degeneration in monkey brain than in mouse brain. Using monkey brain tissues, we found that A53T interacts with neurofascin, an adhesion molecule involved in axon subcellular targeting and neurite outgrowth. Aged monkey brain tissues show an increased interaction of neurofascin with A53T. Overexpression of A53T causes neuritic toxicity in cultured neuronal cells, which can be attenuated by transfected neurofascin. These findings from nonhuman primate brains reveal age-dependent pathological and molecular changes that could contribute to the age-dependent neuropathology in PD. Copyright © 2015 the authors 0270-6474/15/358345-14$15.00/0.

  5. Muusikamaailm : Lahkumiskingitus Udo Zimmermannile. Haitinki esimene "Tristan ja Isolde". Uusooper Garcia Lorca järgi. Schönbergi esietendus Viinis (!) / Priit Kuusk

    Index Scriptorium Estoniae

    Kuusk, Priit, 1938-

    2000-01-01

    U. Zimmermann lahkub Leipzigi Ooperi juhi ja dirigendi kohalt ja asub Deutsche Operi etteotsa Berliinis. B. Haitink juhatab Londoni Kuninglikus Ooperis esmakordselt "Tristani ja Isolde" etendust. A. Reimanni uusooperist "Bernarda Alba maja". A. Schönbergi oratooriumi "Jakobsleiter" esietendusest Viini Riigiooperis

  6. “I am active”: effects of a program to promote active aging

    Science.gov (United States)

    Mendoza-Ruvalcaba, Neyda Ma; Arias-Merino, Elva Dolores

    2015-01-01

    Background Active aging involves a general lifestyle strategy that allows preservation of both physical and mental health during the aging process. “I am Active” is a program designed to promote active aging by increased physical activity, healthy nutritional habits, and cognitive functioning. The purpose of this study was to assess the effectiveness of this program. Methods Sixty-four healthy adults aged 60 years or older were recruited from senior centers and randomly allocated to an experimental group (n=31) or a control group (n=33). Baseline, post-test, and 6-month follow-up assessments were performed after the theoretical–practical intervention. Effect sizes were calculated. Results At the conclusion of the program, the experimental group showed significant improvement compared with the control group in the following domains: physical activity (falls risk, balance, flexibility, self-efficacy), nutrition (self-efficacy and nutritional status), cognitive performance (processing speed and self-efficacy), and quality of life (general, health and functionality, social and economic status). Although some declines were reported, improvements at follow-up remained in self-efficacy for physical activity, self-efficacy for nutrition, and processing speed, and participants had better nutritional status and quality of life overall. Conclusion Our findings show that this program promotes improvements in domains of active aging, mainly in self-efficacy beliefs as well as in quality of life in healthy elders. PMID:26005337

  7. The Relationship between Childhood Maltreatment and Opiate Dependency in Adolescence and Middle Age.

    Science.gov (United States)

    Naqavi, Mohammad Reza; Mohammadi, Masood; Salari, Vahid; Nakhaee, Nouzar

    2011-01-01

    Child maltreatment is a global phenomenon with possible serious long-term consequences. The present study aimed to determine the relationship between childhood maltreatment and opiate dependency in older age. In this study, 212 opiate dependent individuals and 216 control subjects were selected consecutively. The data collection instrument was a questionnaire which consisted of background variables, General Health Questionnaire-12 (GHQ-12), and Childhood Trauma Questionnaire (CTQ). The questionnaires were anonymously completed by both groups in a private environment after obtaining informed consents. The mean age in the addicts and non-addicts were 31.4 ± 6.7 and 30.8 ± 7.5, respectively (P = 0.367). Moreover, 84.4% of the opiate abusers and 76.9% percent of the control group were male (P = 0.051). The mean score of CTQ in the study and control groups were 47.2 ± 1.0 and 35.8 ± 0.6, respectively (P emotional abuse (OR = 5.06), physical neglect (OR = 1.96), and sexual abuse (OR = 1.89) were proved to have significant relationships with addiction to opiates. The frequency of all types of childhood maltreatment in the group addicted to opiates was higher than the control group. Emotional abuse, physical neglect, and sexual abuse had significant effects after adjusting other variables.

  8. Abortion and sex-related conditions in substance-dependent Brazilian patients

    Directory of Open Access Journals (Sweden)

    Alessandra Diehl

    2017-11-01

    Full Text Available Abstract: Abortion is a very sensitive issue with relevance to public health; however few clinical or population-based studies have examined induced abortion among drug users. The study aims to evaluate the prevalence of induced abortion and sex-related conditions in an inpatient drug user sample. A cross-sectional design study was conducted in an inpatient addiction treatment unit in São Paulo, Brazil, with a sample of 616 patients, aged 18-75. Sociodemographic data, sexual behavior, and dependence severity were evaluated in relation to induced abortion. Approximately 27% of patients reported having a history of abortion (themselves in the case of women or partners in the case of men. The mean age was 34.6±10.9 years old, 34.9% diagnosed with severe alcohol dependence, 33% were diagnosed with severe levels of dependence on other drugs, 69.6% were diagnosed cocaine users (inhaled and smoked, and alcohol was the drug of choice for 30.4%. Chances of having a history of abortion is greater for women than for men with a odds ratio (OR = 2.9; 95%CI: 1.75-4.76, (OR = 1.7; 95%CI: 1.09-2.75 of no condom use; (OR = 2.0; 95%CI: 1.35-3.23 of history of STI and (OR = 3.2; 95%CI: 1.29-5.73 use of morning-after pill. Drug- and alcohol-dependent patients have high-risk behaviours of sporadic use or no-condom use which contribute to unplanned pregnancy and induced abortion, making this vulnerable population a group which deserves special attention in sexual health prevention programmes and health promotion efforts for the reduction of induced abortion.

  9. Chemotherapy-related neuropathic symptom management: a randomized trial of an automated symptom-monitoring system paired with nurse practitioner follow-up.

    Science.gov (United States)

    Kolb, Noah Allan; Smith, Albert Gordon; Singleton, John Robinson; Beck, Susan L; Howard, Diantha; Dittus, Kim; Karafiath, Summer; Mooney, Kathi

    2018-05-01

    The purpose of this study was to evaluate a new care model to reduce chemotherapy-induced neuropathic symptoms. Neuropathic symptom usual care was prospectively compared to an automated symptom-monitoring and coaching system, SymptomCare@Home (SCH), which included nurse practitioner follow-up triggered by moderate to severe symptoms. Patients beginning chemotherapy were randomized to usual care (UC) or to the SCH intervention. This sub-analysis included only taxane/platin therapies. Participants called the automated telephone symptom-monitoring system daily to report numbness and tingling. The monitoring system recorded patient-reported neuropathic symptom severity, distress, and activity interference on a 0-10 scale. UC participants were instructed to call their oncologist for symptom management. SCH participants with symptom severity of ≥ 4 received automated self-care strategies, and a nurse practitioner (NP) provided guideline-based care. There were 252 participants, 78.6% of which were female. Mean age was 55.1 years. Mean follow-up was 90.2 ± 39.9 days (81.1 ± 40.3 calls). SCH participants had fewer days of moderate (1.8 ± 4.0 vs. 8.6 ± 17.3, p < 0.001) and severe chemotherapy-induced peripheral neuropathy symptoms (0.3 ± 1.0 vs. 1.1 ± 5.2, p = 0.006). SCH participants had fewer days with moderate and severe symptom-related distress (1.4 ± 3.7 vs. 6.9 ± 15.0, p < 0.001; 0.2 ± 0.9 vs. 1.5 ± 6.1, p = 0.001) and trended towards less activity interference (3.3 ± 1.9 vs. 3.8 ± 2.1, p = 0.08). Other neuropathic symptoms were addressed in 5.8-15.4% of SCH follow-up calls. The SCH system effectively identified neuropathic symptoms and their severity and, paired with NP follow-up, reduced symptom prevalence, severity, and distress compared to usual care.

  10. Promotion of active ageing combining sensor and social network data.

    Science.gov (United States)

    Bilbao, Aritz; Almeida, Aitor; López-de-Ipiña, Diego

    2016-12-01

    The increase of life expectancy in modern society has caused an increase in elderly population. Elderly people want to live independently in their home environment for as long as possible. However, as we age, our physical skills tend to worsen and our social circle tends to become smaller, something that often leads to a considerable decrease of both our physical and social activities. In this paper, we present an AAL framework developed within the SONOPA project, whose objective is to promote active ageing by combining a social network with information inferred using in-home sensors. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Econometric model for age- and population-dependent radiation exposures

    International Nuclear Information System (INIS)

    Sandquist, G.M.; Slaughter, D.M.; Rogers, V.C.

    1991-01-01

    The economic impact associated with ionizing radiation exposures in a given human population depends on numerous factors including the individual's mean economic status as a function age, the age distribution of the population, the future life expectancy at each age, and the latency period for the occurrence of radiation-induced health effects. A simple mathematical model has been developed that provides an analytical methodology for estimating the societal econometrics associated with radiation effects are to be assessed and compared for economic evaluation

  12. Michael Jäckel, Julia Derra, Cornelia Eck: SchönheitsAnsichten. Geschlechterbilder in Werbeanzeigen und ihre Bewertung. Baden-Baden: Nomos Verlag 2009.

    Directory of Open Access Journals (Sweden)

    Waltraud Posch

    2010-11-01

    Full Text Available Michael Jäckel, Julia Derra, and Cornelia Eck’s cross-generational study answers the question as to which concepts of beauty are presented in magazine advertisements and how recipients react to these concepts. The book provides an important basis for Media Studies and Gender Sociology particularly because it also shows medial constructions of gender that are initially invisible and because it shows gender related illustrations of physicality and beauty.In einer generationenübergreifenden Studie gehen Michael Jäckel, Julia Derra und Cornelia Eck der Frage nach, welche Schönheitsbilder in der Zeitschriftenwerbung präsentiert und wie diese von Rezipient/-innen aufgenommen werden. Das Buch liefert eine wichtige Basis für Medienforschung und Soziologie der Geschlechter, zumal es auch vordergründig nicht sichtbare mediale Konstruktionen von Geschlecht und die geschlechtsbezogene Darstellung von Körperlichkeit und Schönheit aufzeigt.

  13. MicroRNA-9 promotes the neuronal differentiation of rat bone marrow mesenchymal stem cells by activating autophagy

    Directory of Open Access Journals (Sweden)

    Guang-yu Zhang

    2015-01-01

    Full Text Available MicroRNA-9 (miR-9 has been shown to promote the differentiation of bone marrow mesenchymal stem cells into neuronal cells, but the precise mechanism is unclear. Our previous study confirmed that increased autophagic activity improved the efficiency of neuronal differentiation in bone marrow mesenchymal stem cells. Accumulating evidence reveals that miRNAs adjust the autophagic pathways. This study used miR-9-1 lentiviral vector and miR-9-1 inhibitor to modulate the expression level of miR-9. Autophagic activity and neuronal differentiation were measured by the number of light chain-3 (LC3-positive dots, the ratio of LC3-II/LC3, and the expression levels of the neuronal markers enolase and microtubule-associated protein 2. Results showed that LC3-positive dots, the ratio of LC3-II/LC3, and expression of neuron specific enolase and microtubule-associated protein 2 increased in the miR-9 + group. The above results suggest that autophagic activity increased and bone marrow mesenchymal stem cells were prone to differentiate into neuronal cells when miR-9 was overexpressed, demonstrating that miR-9 can promote neuronal differentiation by increasing autophagic activity.

  14. State-age-dependent maintenance policies for deteriorating systems with Erlang sojourn time distributions

    International Nuclear Information System (INIS)

    Yeh, R.H.

    1997-01-01

    This paper investigates state-age-dependent maintenance policies for multistate deteriorating systems with Erlang sojourn time distributions. Since Erlang distributions are serial combinations of exponential phases, the deteriorating process can be modeled by a multi-phase Markovian model and hence easily analyzed. Based on the Markovian model, the optimal phase-dependent inspection and replacement policy can be obtained by using a policy improvement algorithm. However, since phases are fictitious and can not be identified by inspections, two procedures are developed to construct state-age-dependent policies based on the optimal phase-dependent policy. The properties of the constructed state-age-dependent policies are further investigated and the performance of the policy is evaluated through a numerical example

  15. Age and dosage-level dependence of radium retention in beagles

    International Nuclear Information System (INIS)

    Parks, N.J.; Pool, R.R.; Williams, J.R.; Wolf, H.G.

    1978-01-01

    Radium retention was measured over the lifespan of 46 beagles exposed by eight semimonthly injections at 60 to 160, 120 to 220, or 435 to 535 days of age. Injection dosage levels ranged from 0.37 to 10 μCi of 226 Ra/kg. The fractional retention of each animal is described in terms of a modified power function, R = [(t + d)/d] - /sup b/. Young adult beagles (approximately equal to 10 kg) injected at a mean age (A) of 485 days with 226 Ra at dosage levels of 10, 3.3, 1.11, and 0.37 μCi/kg had mean values for d and b of [0.897; 0.187], [2.015; 0.206], [2.778; 0.257], and [3.894; 0.274], respectively. Juvenile beagles injected with 10 μCi/kg at A = 110 days (average weight approximately equal to 6 kg) and at A = 170 days (average weight approximately equal to 10 kg) had mean values for d and b of [137; 0.277] and [5.53; 0.086], respectively. The d values are geometric means and the units are days; b values are arithmetic means. The formula for deriving the age-dependent retention function for dogs is given. The beagle results were correlated with human data in terms of age-to-equivalent fraction of adult body calcium content and were used to construct a similar age-dependent retention function for chronically exposed people. The correlation of age-dependent retention functions for beagles and humans is used to estimate scaling factors between the two species for the fraction of injected dosage associated with bone for various ages of exposure

  16. Age-dependent terminal declines in reproductive output in a wild bird.

    Directory of Open Access Journals (Sweden)

    Martijn Hammers

    Full Text Available In many iteroparous species individual fitness components, such as reproductive output, first increase with age and then decline during late-life. However, individuals differ greatly in reproductive lifespan, but reproductive declines may only occur in the period just before their death as a result of an age-independent decline in physiological condition. To fully understand reproductive senescence it is important to investigate to what extent declines in late-life reproduction can be explained by age, time until death, or both. However, the study of late-life fitness performance in natural populations is challenging as the exact birth and death dates of individuals are often not known, and most individuals succumb to extrinsic mortality before reaching old age. Here, we used an exceptional long-term longitudinal dataset of individuals from a natural, closed, and predator-free population of the Seychelles warbler (Acrocephalus sechellensis to investigate reproductive output, both in relation to age and to the time until the death of an individual (reverse-age approach. We observed an initial age-dependent increase in reproductive output that was followed by a decline in old age. However, we found no significant decline in reproductive output in the years directly preceding death. Although post-peak reproductive output declined with age, this pattern differed between terminal and non-terminal reproductive attempts, and the age-dependence of the terminal breeding attempt explained much of the variation in age-specific reproductive output. In fact, terminal declines in reproductive output were steeper in very old individuals. These results indicate that not only age-dependent, but also age-independent factors, such as physiological condition, need to be considered to understand reproductive senescence in wild-living animals.

  17. Dependence on age at intake of committed dose equivalents from radionuclides

    International Nuclear Information System (INIS)

    Adams, N.

    1981-01-01

    The dependence of committed dose equivalents on age at intake is needed to assess the significance of exposures of young persons among the general public resulting from inhaled or ingested radionuclides. The committed dose equivalents, evaluated using ICRP principles, depend on the body dimensions of the young person at the time of intake of a radionuclide and on subsequent body growth. Representation of growth by a series of exponential segments facilitates the derivation of general expressions for the age dependence of committed dose equivalents if metabolic models do not change with age. The additional assumption that intakes of radionuclides in air or food are proportional to a person's energy expenditure (implying age-independent dietary composition) enables the demonstration that the age of the most highly exposed 'critical groups' of the general public from these radionuclides is either about 1 year or 17 years. With the above assumptions the exposure of the critical group is less than three times the exposure of adult members of the general public. Approximate values of committed dose equivalents which avoid both underestimation and excessive overestimation are shown to be obtainable by simplified procedures. Modified procedures are suggested for use if metabolic models change with age. (author)

  18. Cloning and characterization of the promoter of the 9-cis-epoxycarotenoid dioxygenase gene in Arachis hypogaea L.

    Science.gov (United States)

    Liang, Jianhua; Yang, Lixia; Chen, Xiong; Li, Ling; Guo, Dongliang; Li, Haihang; Zhang, Biyu

    2009-09-01

    We cloned the promoter of the 9-cis-epoxycarotenoid dioxygenase gene from Arachis hypogaea L. beta-Glucuronidase (GUS) histochemical staining and GUS activity assay indicated that the activity of the promoter was exhibited predominantly in the leaves and enhanced by water and NaCl stresses, and by application of abscisic acid (ABA) and salicylic acid (SA) in transgenic Arabidopsis. Moreover, two novel ABRE-like (abscisic acid response element) elements were identified in the promoter region.

  19. Microbiota-Dependent Crosstalk Between Macrophages and ILC3 Promotes Intestinal Homeostasis

    Science.gov (United States)

    Mortha, Arthur; Chudnovskiy, Aleksey; Hashimoto, Daigo; Bogunovic, Milena; Spencer, Sean P.; Belkaid, Yasmine; Merad, Miriam

    2014-01-01

    The intestinal microbiota and tissue-resident myeloid cells promote immune responses that maintain intestinal homeostasis in the host. However, the cellular cues that translate microbial signals into intestinal homeostasis remain unclear. Here, we show that deficient granulocyte-macrophage colony-stimulating factor (GM-CSF) production altered mononuclear phagocyte effector functions and led to reduced regulatory T cell (Treg) numbers and impaired oral tolerance. We observed that RORγt+ innate lymphoid cells (ILCs) are the primary source of GM-CSF in the gut and that ILC-driven GM-CSF production was dependent on the ability of macrophages to sense microbial signals and produce interleukin-1β. Our findings reveal that commensal microbes promote a crosstalk between innate myeloid and lymphoid cells that leads to immune homeostasis in the intestine. PMID:24625929

  20. Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis.

    Science.gov (United States)

    Mortha, Arthur; Chudnovskiy, Aleksey; Hashimoto, Daigo; Bogunovic, Milena; Spencer, Sean P; Belkaid, Yasmine; Merad, Miriam

    2014-03-28

    The intestinal microbiota and tissue-resident myeloid cells promote immune responses that maintain intestinal homeostasis in the host. However, the cellular cues that translate microbial signals into intestinal homeostasis remain unclear. Here, we show that deficient granulocyte-macrophage colony-stimulating factor (GM-CSF) production altered mononuclear phagocyte effector functions and led to reduced regulatory T cell (T(reg)) numbers and impaired oral tolerance. We observed that RORγt(+) innate lymphoid cells (ILCs) are the primary source of GM-CSF in the gut and that ILC-driven GM-CSF production was dependent on the ability of macrophages to sense microbial signals and produce interleukin-1β. Our findings reveal that commensal microbes promote a crosstalk between innate myeloid and lymphoid cells that leads to immune homeostasis in the intestine.

  1. Genomic Analysis and Isolation of RNA Polymerase II Dependent Promoters from Spodoptera frugiperda.

    Science.gov (United States)

    Bleckmann, Maren; Fritz, Markus H-Y; Bhuju, Sabin; Jarek, Michael; Schürig, Margitta; Geffers, Robert; Benes, Vladimir; Besir, Hüseyin; van den Heuvel, Joop

    2015-01-01

    The Baculoviral Expression Vector System (BEVS) is the most commonly used method for high expression of recombinant protein in insect cells. Nevertheless, expression of some target proteins--especially those entering the secretory pathway--provides a severe challenge for the baculovirus infected insect cells, due to the reorganisation of intracellular compounds upon viral infection. Therefore, alternative strategies for recombinant protein production in insect cells like transient plasmid-based expression or stable expression cell lines are becoming more popular. However, the major bottleneck of these systems is the lack of strong endogenous polymerase II dependent promoters, as the strong baculoviral p10 and polH promoters used in BEVS are only functional in presence of the viral transcription machinery during the late phase of infection. In this work we present a draft genome and a transcriptome analysis of Sf21 cells for the identification of the first known endogenous Spodoptera frugiperda promoters. Therefore, putative promoter sequences were identified and selected because of high mRNA level or in analogy to other strong promoters in other eukaryotic organism. The chosen endogenous Sf21 promoters were compared to early viral promoters for their efficiency to trigger eGFP expression using transient plasmid based transfection in a BioLector Microfermentation system. Furthermore, promoter activity was not only shown in Sf21 cells but also in Hi5 cells. The novel endogenous Sf21 promoters were ranked according to their activity and expand the small pool of available promoters for stable insect cell line development and transient plasmid expression in insect cells. The best promoter was used to improve plasmid based transient transfection in insect cells substantially.

  2. The age-dependent epigenetic and physiological changes in an Arabidopsis T87 cell suspension culture during long-term cultivation

    Energy Technology Data Exchange (ETDEWEB)

    Kwiatkowska, Aleksandra, E-mail: A.Kwiatkows@gmail.com [Department of Botany, University of Rzeszow, Kolbuszowa (Poland); Zebrowski, Jacek [Department of Plant Physiology, University of Rzeszow, Kolbuszowa (Poland); Oklejewicz, Bernadetta [Department of Genetics, University of Rzeszow, Kolbuszowa (Poland); Czarnik, Justyna [Department of Botany, University of Rzeszow, Kolbuszowa (Poland); Halibart-Puzio, Joanna [Department of Plant Physiology, University of Rzeszow, Kolbuszowa (Poland); Wnuk, Maciej [Department of Genetics, University of Rzeszow, Kolbuszowa (Poland)

    2014-05-02

    Highlights: • A decrease in proliferation rate during long-term cultivation of Arabidopsis cells. • Age-dependent increase in senescence-associated gene expression in Arabidopsis cells. • Age-related increase in DNA methylation, H3K9me2, and H3K27me3 in Arabidopsis cells. • High potential of photosynthetic efficiency of long-term cultured Arabidopsis cells. - Abstract: Plant cell suspension cultures represent good model systems applicable for both basic research and biotechnological purposes. Nevertheless, it is widely known that a prolonged in vitro cultivation of plant cells is associated with genetic and epigenetic instabilities, which may limit the usefulness of plant lines. In this study, the age-dependent epigenetic and physiological changes in an asynchronous Arabidopsis T87 cell culture were examined. A prolonged cultivation period was found to be correlated with a decrease in the proliferation rate and a simultaneous increase in the expression of senescence-associated genes, indicating that the aging process started at the late growth phase of the culture. In addition, increases in the heterochromatin-specific epigenetic markers, i.e., global DNA methylation, H3K9 dimethylation, and H3K27 trimethylation, were observed, suggesting the onset of chromatin condensation, a hallmark of the early stages of plant senescence. Although the number of live cells decreased with an increase in the age of the culture, the remaining viable cells retained a high potential to efficiently perform photosynthesis and did not exhibit any symptoms of photosystem II damage.

  3. The age-dependent epigenetic and physiological changes in an Arabidopsis T87 cell suspension culture during long-term cultivation

    International Nuclear Information System (INIS)

    Kwiatkowska, Aleksandra; Zebrowski, Jacek; Oklejewicz, Bernadetta; Czarnik, Justyna; Halibart-Puzio, Joanna; Wnuk, Maciej

    2014-01-01

    Highlights: • A decrease in proliferation rate during long-term cultivation of Arabidopsis cells. • Age-dependent increase in senescence-associated gene expression in Arabidopsis cells. • Age-related increase in DNA methylation, H3K9me2, and H3K27me3 in Arabidopsis cells. • High potential of photosynthetic efficiency of long-term cultured Arabidopsis cells. - Abstract: Plant cell suspension cultures represent good model systems applicable for both basic research and biotechnological purposes. Nevertheless, it is widely known that a prolonged in vitro cultivation of plant cells is associated with genetic and epigenetic instabilities, which may limit the usefulness of plant lines. In this study, the age-dependent epigenetic and physiological changes in an asynchronous Arabidopsis T87 cell culture were examined. A prolonged cultivation period was found to be correlated with a decrease in the proliferation rate and a simultaneous increase in the expression of senescence-associated genes, indicating that the aging process started at the late growth phase of the culture. In addition, increases in the heterochromatin-specific epigenetic markers, i.e., global DNA methylation, H3K9 dimethylation, and H3K27 trimethylation, were observed, suggesting the onset of chromatin condensation, a hallmark of the early stages of plant senescence. Although the number of live cells decreased with an increase in the age of the culture, the remaining viable cells retained a high potential to efficiently perform photosynthesis and did not exhibit any symptoms of photosystem II damage

  4. “I am active”: effects of a program to promote active aging

    Directory of Open Access Journals (Sweden)

    Mendoza-Ruvalcaba NM

    2015-05-01

    Full Text Available Neyda Ma Mendoza-Ruvalcaba,1 Elva Dolores Arias-Merino2 1Health Sciences Department, University of Guadalajara, University Center of Tonala Guadalajara, Jalisco, Mexico; 2Public Health Department, University of Guadalajara, University Center of Health Sciences, Guadalajara, Jalisco, Mexico Background: Active aging involves a general lifestyle strategy that allows preservation of both physical and mental health during the aging process. “I am Active” is a program designed to promote active aging by increased physical activity, healthy nutritional habits, and cognitive functioning. The purpose of this study was to assess the effectiveness of this program. Methods: Sixty-four healthy adults aged 60 years or older were recruited from senior centers and randomly allocated to an experimental group (n=31 or a control group (n=33. Baseline, post-test, and 6-month follow-up assessments were performed after the theoretical–practical intervention. Effect sizes were calculated. Results: At the conclusion of the program, the experimental group showed significant improvement compared with the control group in the following domains: physical activity (falls risk, balance, flexibility, self-efficacy, nutrition (self-efficacy and nutritional status, cognitive performance (processing speed and self-efficacy, and quality of life (general, health and functionality, social and economic status. Although some declines were reported, improvements at follow-up remained in self-efficacy for physical activity, self-efficacy for nutrition, and processing speed, and participants had better nutritional status and quality of life overall. Conclusion: Our findings show that this program promotes improvements in domains of active aging, mainly in self-efficacy beliefs as well as in quality of life in healthy elders. Keywords: active aging, successful aging, intervention program, randomized controlled trial

  5. The Salutogenic Wellness Promotion Scale for Older Adults

    Science.gov (United States)

    Becker, Craig M.; Chaney, Beth H.; Shores, Kindal; Glascoff, Mary

    2015-01-01

    Background: From 1990 to 2050, the population aged 60 years and older will rise from 9% to 21%. Healthy aging initiatives are vital to promote individual, community, and global well-being during this transformation. Accurate health measurement tools are needed to successfully guide strategies and plot progress. The validated multi-dimensional…

  6. Promoting Positive Attitudes of Kindergarten-Age Children toward People with Disabilities.

    Science.gov (United States)

    Favazza, Paddy C.; Odom, Samuel L.

    1997-01-01

    This study examined the effects of contact, books, and discussions on attitudes of kindergarten-age children (N=46) toward people with disabilities. At posttest, significant gains in acceptance were found only in a high-contact group who participated in a program designed to promote acceptance through storytime at school and home, structured play,…

  7. Palladium-catalyzed heteroannulation approach to 7-azatryptophan with a Schöllkopf chiral auxiliary

    Energy Technology Data Exchange (ETDEWEB)

    Gee, Moon Bae; Kim, Tae Seung; Yun, Eul Kgun [Dept. of Chemistry, Chungnam National University, Daejeon (Korea, Republic of)

    2015-05-15

    Our previous results on heteroannulation with unprotected 2-amino-3-iodopyridine and internal alkynes showed very low yields of the annulated product. The synthetic limitation could be due to the low nucleophilicity of the nitrogen that exists in the three tautomeric forms of 2-amino-pyridine (Scheme 1) or to the easy formation of a palladium complex with 2-aminopyridine. First, we examined the synthesis of the azaindole precursor, followed by reaction with a Schöllkopf chiral auxiliary. The heteroannulation provided the desired annulated product 5 in 60% yield, along with an uncyclized Sonogawasihra coupling product. After purifying product 5 by column chromatography, it was converted to 7-aza-tryptophan.

  8. Vergleich verschiedener Beurteilungsverfahren an Röntgenbildern des Ellbogengelenkes beim Deutschen Schäferhund und Rottweiler unter Berücksichtigung des Einflusses der Lagerung als Basis einer züchterischen Selektion gegen die Ellbogengelenksdysplasie

    OpenAIRE

    Klein, Sandra

    2010-01-01

    Ziel dieser Untersuchung war es, drei Bewertungsverfahren zur Beurteilung der Ellbogengelenksdysplasie bei Hunden der Rasse Deutscher Schäferhund und Rottweiler miteinander zu vergleichen. Hierbei sollte insbesondere ein Einfluss der Lagerung während der Röntgenaufnahme überprüft werden. Bewertet wurden Röntgenaufnahmen von 19.798 Deutschen Schäferhunden und 2.430 Rottweiler, von denen bereits ein offizieller ED – Befund vorlag. Es erfolgte eine Beurteilung entsprechend der zwei Punktesch...

  9. Púrpura de Henoch-Schönlein com acometimento incomum de face Unusual face involvement in Henoch-Schönlein purpura

    Directory of Open Access Journals (Sweden)

    Carolina Bassoli de Azevedo

    2009-12-01

    Full Text Available A Púrpura de Henoch-Shönlein é uma vasculite de causa idiopática, que se caracteriza pelo depósito predominante de IgA na parede dos pequenos vasos, envolvendo tipicamente pele, intestino, articulações e glomérulo renal. O acometimento cutâneo ocorre principalmente em membros inferiores e região glútea, sendo raramente encontrado em face e membros superiores. Relatamos o caso de uma paciente do sexo feminino, com seis anos de idade, que apresentava lesões púrpuricas em região auricular, periorbital, malar, mentoniana e membros superiores, além de artralgia e volvo intestinal. Após tratamento cirúrgico e pulsoterapia com glicocorticoide, houve regressão dos sintomas, sem maiores complicações.Henoch-Schönlein Purpura is an idiopathic vasculitis characterized by deposits of immunoglobulin, mainly IgA, on the walls of small vessels, typically involving the skin, gut, joints, and renal glomeruli. Cutaneous involvement affects specially the lower limbs and buttocks, and it is seldom found on the face and upper limbs. We report the case of a 6-year old girl with purpuric lesions over the auricular, periorbital, malar, and mentonian regions and the upper limbs, arthralgia, and intestinal torsion. After surgical treatment and pulse therapy with glucocorticoids, her symptoms subsided without further complications.

  10. Is late-life dependency increasing or not? A comparison of the Cognitive Function and Ageing Studies (CFAS).

    Science.gov (United States)

    Kingston, Andrew; Wohland, Pia; Wittenberg, Raphael; Robinson, Louise; Brayne, Carol; Matthews, Fiona E; Jagger, Carol

    2017-10-07

    Little is known about how the proportions of dependency states have changed between generational cohorts of older people. We aimed to estimate years lived in different dependency states at age 65 years in 1991 and 2011, and new projections of future demand for care. In this population-based study, we compared two Cognitive Function and Ageing Studies (CFAS I and CFAS II) of older people (aged ≥65 years) who were permanently registered with a general practice in three defined geographical areas (Cambridgeshire, Newcastle, and Nottingham; UK). These studies were done two decades apart (1991 and 2011). General practices provided lists of individuals to be contacted and were asked to exclude those who had died or might die over the next month. Baseline interviews were done in the community and care homes. Participants were stratified by age, and interviews occurred only after written informed consent was obtained. Information collected included basic sociodemographics, cognitive status, urinary incontinence, and self-reported ability to do activities of daily living. CFAS I was assigned as the 1991 cohort and CFAS II as the 2011 cohort, and both studies provided prevalence estimates of dependency in four states: high dependency (24-h care), medium dependency (daily care), low dependency (less than daily), and independent. Years in each dependency state were calculated by Sullivan's method. To project future demands for social care, the proportions in each dependency state (by age group and sex) were applied to the 2014 UK [corrected] population projections. Between 1991 and 2011, there were significant increases in years lived from age 65 years with low dependency (1·7 years [95% CI 1·0-2·4] for men and 2·4 years [1·8-3·1] for women) and increases with high dependency (0·9 years [0·2-1·7] for men and 1·3 years [0·5-2·1] for women). The majority of men's extra years of life were spent independent (36·3%) or with low dependency (36·3%) whereas for women

  11. Age differences in empathy: Multidirectional and context-dependent.

    Science.gov (United States)

    Wieck, Cornelia; Kunzmann, Ute

    2015-06-01

    This study investigated age differences in empathy, focusing on empathic accuracy (the ability to perceive another's emotions accurately), emotional congruence (the capacity to share another's emotions), and sympathy. Participants, 101 younger (Mage = 24 years) and 101 older (Mage = 69 years) women, viewed 6 film clips, each portraying a younger or an older woman reliving and thinking aloud about an autobiographical memory. The emotional quality (anger, sadness, happiness) and the age relevance (young, old) of the memorized events were systematically varied. In comparison to their younger counterparts, older women were less accurate in perceiving the protagonists' emotions, but they reported similar levels of emotional congruence and greater sympathy. In addition, age deficits in empathic accuracy were moderated by the age relevance of the task, that is, younger and older women's empathic accuracy did not differ if the protagonists' memorized personal experience was of high relevance to older adults. These findings speak for multidirectional and context-dependent age differences in empathy. (c) 2015 APA, all rights reserved.

  12. Vision screening in children: Is 7-9 years of age a threshold for visual impairment?

    Science.gov (United States)

    Ertekin, Yusuf Haydar; Tekin, Murat; Uludag, Aysegul; Arikan, Sedat; Sahin, Erkan Melih

    2016-01-01

    The present study aimed to assess the prevalence of decreased visual acuity, strabismus, and spectacle wear in children aged 5 to 13 years. A cross-sectional study was performed in primary education schools. A total of 1938 participants, including 940 females (48.5%) and 998 males (51.5%) with a mean age 8.96 ± 2.31 (5-13 years old), were screened. The comparisons were performed with gender, age, and age groups. The children attended to vision screening were assigned to three age groups as 5-6 years, 7-9 years, and 10-13 years. The prevalence of the parameters was detected as decreased visual acuity 12.4%, strabismus 2.2%, and spectacle wear 6.9%. The prevalence of decreased visual acuity was significantly higher in girls and in children aged 7-9 years old (p = 0.013, p children aged 7-9 years old (p = 0.019, p visual acuity decrease in 33 of 106 (31.1%) children despite wearing own spectacle. There was no significant difference among three age groups for strabismus. Increased prevalence of decreased visual acuity, as well as the higher frequency of spectacle wear in children at ages of 7-9 years old may point out a threshold for visual impairment.

  13. An exploration of health concerns & health-promotion behaviors in pregnant women over age 35.

    Science.gov (United States)

    Viau, Paula A; Padula, Cynthia A; Eddy, Barbara

    2002-01-01

    To explore the specific health concerns and health-promotion behaviors of childbearing women 35 years of age or older. Semistructured interviews with women ( = 50) ages > or =35 in their third trimester of pregnancy. Interviews lasted approximately 1 hour, were conducted by two nursing faculty, and were scheduled to accommodate participant needs. Process recording was used to document participant responses. Verbatim statements were recorded, and subjects were redirected to clarify responses when necessary. Content analysis and coding were completed by an independent researcher, based upon techniques derived from Miles and Huberman (1994). Data reduction was accomplished by the identification of categories of responses that described the participants' meaning. Study participants reported concerns reflecting both fetal well-being and maternal health-related issues. The majority of childbearing women (86%) reported engaging in multiple health-promotion behaviors focusing on daily nutritional intake, lifestyle activities, and rest patterns. Participants reported conscientious decisions to eliminate substances recognized as harmful, and to alter exercise, employment, or daily responsibilities to accommodate physical changes during pregnancy. Participants were "proactive healthcare seekers," accessing information from a variety of sources and seeking services to meet their individualized needs. The multitude and frequency of health-promotion behaviors adopted by those > or =35 years of age during pregnancy is indicative of this group's ability to independently initiate change, and exceeds the percentages previously reported. The nurse can be influential in supporting lifestyle modifications adopted during the childbearing period as permanent health-promotion behaviors.

  14. On the dynamics of the age structure, dependency, and consumption

    Science.gov (United States)

    Hock, Heinrich

    2013-01-01

    We examine the effects of population aging due to declining fertility and rising elderly life expectancy on consumption possibilities in the presence of intergenerational transfers. Our analysis is based on a highly tractable continuous-time overlapping generations model in which the population is divided into three groups (youth dependents, workers, and elderly dependents) and lifecourse transitions take place in a probabilistic fashion. We show that the consumption-maximizing response to greater longevity in highly developed countries is an increase in fertility. However, with larger transfer payments, the actual fertility response will likely be the opposite, leading to further population aging. PMID:24353374

  15. Gelatin-Derived Graphene–Silicate Hybrid Materials Are Biocompatible and Synergistically Promote BMP9-Induced Osteogenic Differentiation of Mesenchymal Stem Cells

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Yulong [Department of Orthopaedic; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois 60637, United States; Qazvini, Nader Taheri [Institute for Molecular Engineering, The University of Chicago, Chicago, Illinois 60637, United States; Argonne National Laboratory, Argonne, Illinois 60439, United States; Zane, Kylie [Institute for Molecular Engineering, The University of Chicago, Chicago, Illinois 60637, United States; Sadati, Monirosadat [Institute for Molecular Engineering, The University of Chicago, Chicago, Illinois 60637, United States; Argonne National Laboratory, Argonne, Illinois 60439, United States; Wei, Qiang [Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois 60637, United States; Ministry of Education Key Laboratory of; Liao, Junyi [Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois 60637, United States; Ministry of Education Key Laboratory of; Fan, Jiaming [Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois 60637, United States; Ministry of Education Key Laboratory of; Song, Dongzhe [Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois 60637, United States; Department of Conservative Dentistry and Endodontics, West China School of Stomatology, Sichuan University, Chengdu 610041, China; Liu, Jianxiang [Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois 60637, United States; Department; amp, Technology, Wuhan 430022, China; Ma, Chao [Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois 60637, United States; Departments of Neurosurgery and Otolaryngology-Head; amp, Neck Surgery, The Affiliated Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Qu, Xiangyang [Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois 60637, United States; Ministry of Education Key Laboratory of; Chen, Liqun [Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois 60637, United States; Ministry of Education Key Laboratory of; Yu, Xinyi [Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois 60637, United States; Ministry of Education Key Laboratory of; Zhang, Zhicai [Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois 60637, United States; Department; amp, Technology, Wuhan 430022, China; Zhao, Chen [Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois 60637, United States; Ministry of Education Key Laboratory of; Zeng, Zongyue [Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois 60637, United States; Ministry of Education Key Laboratory of; Zhang, Ruyi [Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois 60637, United States; Ministry of Education Key Laboratory of; Yan, Shujuan [Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois 60637, United States; Ministry of Education Key Laboratory of; Wu, Tingting [Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois 60637, United States; Departments of Neurosurgery and Otolaryngology-Head; amp, Neck Surgery, The Affiliated Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Wu, Xingye [Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois 60637, United States; Ministry of Education Key Laboratory of; Shu, Yi [Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois 60637, United States; Ministry of Education Key Laboratory of; Li, Yasha [Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois 60637, United States; Ministry of Education Key Laboratory of; Zhang, Wenwen [Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois 60637, United States; Department; Reid, Russell R. [Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois 60637, United States; Department of Surgery, Section of Plastic; Lee, Michael J. [Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois 60637, United States; Wolf, Jennifer Moritis [Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois 60637, United States; Tirrell, Matthew [Institute for Molecular Engineering, The University of Chicago, Chicago, Illinois 60637, United States; Argonne National Laboratory, Argonne, Illinois 60439, United States; He, Tong-Chuan [Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois 60637, United States; Ministry of Education Key Laboratory of; de Pablo, Juan J. [Institute for Molecular Engineering, The University of Chicago, Chicago, Illinois 60637, United States; Argonne National Laboratory, Argonne, Illinois 60439, United States; Deng, Zhong-Liang [Department of Orthopaedic

    2017-05-04

    Graphene-based materials are used in many fields but have found only limited applications in biomedicine, including bone tissue engineering. Here, we demonstrate that novel hybrid materials consisting of gelatin-derived graphene and silicate nanosheets of Laponite (GL) are biocompatible and promote osteogenic differentiation of mesenchymal stem cells (MSCs). Homogeneous cell attachment, long-term proliferation, and osteogenic differentiation of MSCs on a GL-scaffold were confirmed using optical microscopy and scanning electron microscopy. GL-powders made by pulverizing the GL-scaffold were shown to promote bone morphogenetic protein (BMP9)-induced osteogenic differentiation. GL-powders increased the alkaline phosphatase (ALP) activity in immortalized mouse embryonic fibroblasts but decreased the ALP activity in more-differentiated immortalized mouse adipose-derived cells. Note, however, that GL-powders promoted BMP9-induced calcium mineral deposits in both MSC lines, as assessed using qualitative and quantitative alizarin red assays. Furthermore, the expression of chondro-osteogenic regulator markers such as Runx2, Sox9, osteopontin, and osteocalcin was upregulated by the GL-powder, independent of BMP9 stimulation; although the powder synergistically upregulated the BMP9-induced Osterix expression, the adipogenic marker PPAR gamma was unaffected. Furthermore, in vivo stem cell implantation experiments demonstrated that GL-powder could significantly enhance the BMP9-induced ectopic bone formation from MSCs. Collectively, our results strongly suggest that the GL hybrid materials promote BMP9-induced osteogenic differentiation of MSCs and hold promise for the development of bone tissue engineering platforms.

  16. Amyloid-beta transporter expression at the blood-CSF barrier is age-dependent

    Directory of Open Access Journals (Sweden)

    Pascale Crissey L

    2011-07-01

    Full Text Available Abstract Background Age is the major risk factor for many neurodegenerative diseases, including Alzheimer's disease (AD. There is an accumulation of amyloid-beta peptides (Aβ in both the AD brain and the normal aging brain. Clearance of Aβ from the brain occurs via active transport at the blood-brain barrier (BBB and blood-cerebrospinal fluid barrier (BCSFB. With increasing age, the expression of the Aβ efflux transporters is decreased and the Aβ influx transporter expression is increased at the BBB, adding to the amyloid burden in the brain. Expression of the Aβ transporters at the choroid plexus (CP epithelium as a function of aging was the subject of this study. Methods This project investigated the changes in expression of the Aβ transporters, the low density lipoprotein receptor-related protein-1 (LRP-1, P-glycoprotein (P-gp, LRP-2 (megalin and the receptor for advanced glycation end-products (RAGE at the BCSFB in Brown-Norway/Fischer rats at ages 3, 6, 9, 12, 20, 30 and 36 months, using real time RT-PCR to measure transporter mRNA expression, and immunohistochemistry (IHC to measure transporter protein in isolated rat CP. Results There was an increase in the transcription of the Aβ efflux transporters, LRP-1 and P-gp, no change in RAGE expression and a decrease in LRP-2, the CP epithelium influx transporter, at the BCSFB with aging. Decreased Aβ42 concentration in the CP, as measured by quantitative IHC, was associated with these Aβ transporter alterations. Conclusions Age-dependent alterations in the CP Aβ transporters are associated with a decrease in Aβ42 accumulation in the CP, and are reciprocal to the changes seen in these transporters at the BBB, suggesting a possible compensatory role for the BCSFB in Aβ clearance in aging.

  17. Exercise benefits for the aging brain depend on the accompanying cognitive load: insights from sleep electroencephalogram.

    Science.gov (United States)

    Horne, Jim

    2013-11-01

    Although exercise clearly offsets aging effects on the body, its benefits for the aging brain are likely to depend on the extent that physical activity (especially locomotion) facilitates multisensory encounters, curiosity, and interactions with novel environments; this is especially true for exploratory activity, which occupies much of wakefulness for most mammals in the wild. Cognition is inseparable from physical activity, with both interlinked to promote neuroplasticity and more successful brain aging. In these respects and for humans, exercising in a static, featureless, artificially lit indoor setting contrasts with exploratory outdoor walking within a novel environment during daylight. However, little is known about the comparative benefits for the aging brain of longer-term daily regimens of this latter nature including the role of sleep, to the extent that sleep enhances neuroplasticity as shown in short-term laboratory studies. More discerning analyses of sleep electroencephalogram (EEG) slow-wave activity especially 0.5-2-Hz activity would provide greater insights into use-dependent recovery processes during longer-term tracking of these regimens and complement slower changing waking neuropsychologic and resting functional magnetic resonance imaging (fMRI) measures, including those of the brain's default mode network. Although the limited research only points to ephemeral small sleep EEG effects of pure exercise, more enduring effects seem apparent when physical activity incorporates cognitive challenges. In terms of "use it or lose it," curiosity-driven "getting out and about," encountering, interacting with, and enjoying novel situations may well provide the brain with its real exercise, further reflected in changes to the dynamics of sleep. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Influence of tritium aging on kinetics feature of LaNi4.9Al0.1

    International Nuclear Information System (INIS)

    Xiong Yifu; Luo Deli; Li Rong

    2001-01-01

    Kinetics parameters were measured at different aging time on LaNi 4.9 Al 0.1 alloy. The influence of tritium aging on kinetics feature of LaNi 4.9 Al 0.1 alloy was assessed. The results show that tritium aging does not change deuterating-dedeuterating reaction order. Reaction rate decrease with aging time. Activation energy (E) increases with aging time

  19. Age-Dependent and Lineage-Dependent Speciation and Extinction in the Imbalance of Phylogenetic Trees.

    Science.gov (United States)

    Holman, Eric W

    2017-11-01

    It is known that phylogenetic trees are more imbalanced than expected from a birth-death model with constant rates of speciation and extinction, and also that imbalance can be better fit by allowing the rate of speciation to decrease as the age of the parent species increases. If imbalance is measured in more detail, at nodes within trees as a function of the number of species descended from the nodes, age-dependent models predict levels of imbalance comparable to real trees for small numbers of descendent species, but predicted imbalance approaches an asymptote not found in real trees as the number of descendent species becomes large. Age-dependence must therefore be complemented by another process such as inheritance of different rates along different lineages, which is known to predict insufficient imbalance at nodes with few descendent species, but can predict increasing imbalance with increasing numbers of descendent species. [Crump-Mode-Jagers process; diversification; macroevolution; taxon sampling; tree of life.]. © The Author(s) 2017. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Age-dependent male mating investment in Drosophila pseudoobscura.

    Directory of Open Access Journals (Sweden)

    Sumit Dhole

    Full Text Available Male mating investment can strongly influence fitness gained from a mating. Yet, male mating investment often changes with age. Life history theory predicts that mating investment should increase with age, and males should become less discriminatory about their mate as they age. Understanding age-dependent changes in male behavior and their effects on fitness is important for understanding how selection acts in age-structured populations. Although the independent effects of male or female age have been studied in many species, how these interact to influence male mating investment and fitness is less well understood. We mated Drosophila pseudoobscura males of five different age classes (4-, 8-, 11-, 15-, 19-day old to either young (4-day or old (11-day females, and measured copulation duration and early post-mating fecundity. Along with their independent effects, we found a strong interaction between the effects of male and female ages on male mating investment and fitness from individual matings. Male mating investment increased with male age, but this increase was more prominent in matings with young females. Male D. pseudoobscura made smaller investments when mating with old females. The level of such discrimination based on female age, however, also changed with male age. Intermediate aged males were most discriminatory, while the youngest and the oldest males did not discriminate between females of different ages. We also found that larger male mating investments resulted in higher fitness payoffs. Our results show that male and female ages interact to form a complex pattern of age-specific male mating investment and fitness.

  1. Henoch-Schönlein purpura nephritis occurring postpartum in a patient with anti-PL-7 anti-synthetase syndrome.

    Science.gov (United States)

    Nagai, Kojiro; Kishi, Jun; Morizumi, Shun; Minakuchi, Jun; Bando, Yoshimi; Nishioka, Yasuhiko; Doi, Toshio

    2017-09-01

    A 37-year-old pregnant woman developed purpura which was subsequently diagnosed as Henoch-Schönlein purpura (HSP). After childbirth, the patient developed proteinuria and hematuria. Further examination revealed that the HSP nephritis (HSPN) was associated with anti-threonyl-tRNA synthetase anti-synthetase syndrome. The onset of HSPN during pregnancy or after childbirth is rare. Moreover, to our knowledge, this is the first case to describe renal involvement in anti-synthetase syndrome.

  2. Age-Dependent Metabolic and Immunosuppressive Effects of Tacrolimus.

    Science.gov (United States)

    Krenzien, F; Quante, M; Heinbokel, T; Seyda, M; Minami, K; Uehara, H; Biefer, H R C; Schuitenmaker, J M; Gabardi, S; Splith, K; Schmelzle, M; Petrides, A K; Azuma, H; Pratschke, J; Li, X C; ElKhal, A; Tullius, S G

    2017-05-01

    Immunosuppression in elderly recipients has been underappreciated in clinical trials. Here, we assessed age-specific effects of the calcineurin inhibitor tacrolimus (TAC) in a murine transplant model and assessed its clinical relevance on human T cells. Old recipient mice exhibited prolonged skin graft survival compared with young animals after TAC administration. More important, half of the TAC dose was sufficient in old mice to achieve comparable systemic trough levels. TAC administration was able to reduce proinflammatory interferon-γ cytokine production and promote interleukin-10 production in old CD4 + T cells. In addition, TAC administration decreased interleukin-2 secretion in old CD4 + T cells more effectively while inhibiting the proliferation of CD4 + T cells in old mice. Both TAC-treated murine and human CD4 + T cells demonstrated an age-specific suppression of intracellular calcineurin levels and Ca 2+ influx, two critical pathways in T cell activation. Of note, depletion of CD8 + T cells did not alter allograft survival outcome in old TAC-treated mice, suggesting that TAC age-specific effects were mainly CD4 + T cell mediated. Collectively, our study demonstrates age-specific immunosuppressive capacities of TAC that are CD4 + T cell mediated. The suppression of calcineurin levels and Ca 2+ influx in both old murine and human T cells emphasizes the clinical relevance of age-specific effects when using TAC. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  3. Aging in Colombia

    Directory of Open Access Journals (Sweden)

    María Lourdes SANTOS PÉREZ

    2015-12-01

    Full Text Available Using data from statistical sources and official reports, we propose a critical approach to aging in Colombia, specifically from the point of view of public policy in progress or in planning. Our main hypothesis is that these measures refuse comprehensive treatment of the ageing in terms of needs and rights promoting a pure welfare system which, instead, contributes to reinforce a collective imagination of a dependent and impoverished old age, with «fatal» consequences that sustain and reproduce the socioeconomic system.

  4. Age dependent T2 changes of bone marrow in pediatric wrist MRI

    International Nuclear Information System (INIS)

    Shabshin, Nogah; Schweitzer, Mark E.

    2009-01-01

    Hyperintensity of the bone marrow on fluid-sensitive sequences can be seen on magnetic resonance imaging (MRI) during childhood, even in the absence of bone pathology. They can be related to hematopoietic marrow, normal and abnormal bone remodeling. We sought to investigate whether hyper intensity of the bone marrow on MRI of the wrist is age-dependent and to evaluate if this signal follows a consistent age-related pattern. Thirty-one wrist 1.5 T MR images of children (7-18 years) without suspected bone pathology were evaluated for foci of hyperintense bone marrow seen on fluid-sensitive coronal sequences using a scale of 1-3. Correlation of frequency, location and intensity of these foci with age was obtained. Results were analyzed for distribution in single bones and in the following regions: distal forearm, first/second carpal rows, and metacarpal bases. A total of 448 bones were evaluated. Eighty-eight out of 448 (21 out of 31 wrists) showed hyperintense bone marrow seen on fluid-sensitive sequences. The distribution was: radius in 19, ulna in 19, first metacarpal base in 11, scaphoid in 9, lunate in 6, pisiform in 6, and fifth metacarpal base in 1. The involvement of the first and second carpal rows and the metacarpal bases was almost similar (13, 12, and 12 respectively). In the distal forearm, the intensity was similar to or higher than that in the wrist (2.2 vs. 2.0). Frequency decreased with age (100% at 7-9 and 25% at 16-18 years). Foci of hyperintense bone marrow seen on fluid-sensitive sequences can be seen on MRI of the wrist during childhood even without apparent symptoms. It shows a consistent pattern with maturation: frequency and intensity decrease and there is distal-to-proximal resolution. This may be a normal finding that may represent normal bone remodeling or decreasing hematopoietic marrow and should not be confused with pathological bone marrow edema. (orig.)

  5. Recent trends in television tip over-related injuries among children aged 0-9 years.

    Science.gov (United States)

    Murray, K J; Griffin, R; Rue, L W; McGwin, G

    2009-08-01

    To describe recent trends in television tip over-related injuries among children aged 0-9 years, and to compare injury rates with sales of newer digital televisions. Digital television sales data were obtained from marketing data provided by the Television Bureau of Advertising. Data regarding television tip over-related injuries among children aged 0-9 years were obtained from the 1998-2007 National Electronic Injury Surveillance System. A Wald chi(2) test, estimated from logistic analysis, was used to determine whether the distribution of injury types differed by age group. Pearson's correlation was used to estimate the association between digital television sales and television tip over-related injuries. An estimated 42 122 (95% CI 35 199 to 49 122) injuries from television tip-overs were treated in US emergency departments from 1998 to 2007. The injury rate was highest for children aged 1-4 years (18.6/100 000). A majority of injuries (63.9%) involved the head and neck for children under 1 year of age, while a higher proportion of injuries among children aged 1-4 involved the hip and lower extremity (42.9% and 31.0%, respectively), and shoulder and upper extremity (16.8%) for children aged 5-9. A strong, positive correlation was observed between television sales and annual injury rates (r = 0.89, pdigital television sales were strongly correlated with increased injury rates, the lack of information regarding the type of television involved prevents inference regarding causation.

  6. Age-dependent decline in acyl-ghrelin concentrations and reduced association of acyl-ghrelin and growth hormone in healthy older adults.

    Science.gov (United States)

    Nass, Ralf; Farhy, Leon S; Liu, Jianhua; Pezzoli, Suzan S; Johnson, Michael L; Gaylinn, Bruce D; Thorner, Michael O

    2014-02-01

    Acyl-ghrelin is thought to have both orexigenic effects and to stimulate GH release. A possible cause of the anorexia of aging is an age-dependent decrease in circulating acyl-ghrelin levels. The purpose of the study was to compare acyl-ghrelin and GH concentrations between healthy old and young adults and to examine the relationship of acyl-ghrelin and GH secretion in both age groups. Six healthy older adults (age 62-74 y, body mass index range 20.9-29 kg/m(2)) and eight healthy young men (aged 18-28 y, body mass index range 20.6-26.2 kg/m(2)) had frequent blood samples drawn for hormone measurements every 10 minutes for 24 hours. Ghrelin was measured in an in-house, two-site sandwich ELISA specific for full-length acyl-ghrelin. GH was measured in a sensitive assay (Immulite 2000), and GH peaks were determined by deconvolution analysis. The acyl-ghrelin/GH association was estimated from correlations between amplitudes of individual GH secretory events and the average acyl-ghrelin concentration in the 60-minute interval preceding each GH burst. Twenty-four-hour mean (±SEM) GH (0.48 ± 0.14 vs 2.2 ± 0.3 μg/L, P adults compared with young adults. Twenty-four-hour cortisol concentrations were higher in the old than the young adults (15.1 ± 1.0 vs 10.6 ± 0.9 μg/dL, respectively, P young adults (0.16 ± 0.12 vs 0.69 ± 0.04, P age-dependent decline in circulating acyl-ghrelin levels, which might play a role both in the decline of GH and in the anorexia of aging. Our data also suggest that with normal aging, endogenous acyl-ghrelin levels are less tightly linked to GH regulation.

  7. Overexpression of TIMP-1 under the MMP-9 promoter interferes with wound healing in transgenic mice

    OpenAIRE

    Salonurmi, T.; Parikka, M.; Kontusaari, S.; Pirila, E.; Munaut, Carine; Salo, T.; Tryggvason, K.

    2004-01-01

    We have generated transgenic mice harboring the murine matrix metalloproteinase 9 (MMP-9) promoter cloned in front of human TIMP-1 cDNA. The transgenic mice were viable and fertile and exhibited normal growth and general development. During wound healing the mice were shown to express human TIMP-1 in keratinocytes that normally express MMP-9. However, the healing of skin wounds was significantly retarded with slow migration of keratinocytes over the wound in transgenic mice. In situ zymograph...

  8. How aging affects sleep-dependent memory consolidation?

    Directory of Open Access Journals (Sweden)

    Caroline eHarand

    2012-02-01

    Full Text Available Sleep plays multiple functions among which energy conservation or recuperative processes. Besides, growing evidence indicate that sleep plays also a major role in memory consolidation, a process by which recently acquired and labile memory traces are progressively strengthened into more permanent and/or enhanced forms. Indeed, memories are not stored as they were initially encoded but rather undergo a gradual reorganization process, which is favoured by the neurochemical environment and the electrophysiological activity observed during sleep. Two putative, probably not exclusive, models (hippocampo-neocortical dialogue and synaptic homeostasis hypothesis have been proposed to explain the beneficial effect of sleep on memory processes. It is worth noting that all data gathered until now emerged from studies conducted in young subjects. The investigation of the relationships between sleep and memory in older adults has sparked off little interest until recently. Though, aging is characterized by memory impairment, changes in sleep architecture, as well as brain and neurochemical alterations. All these elements suggest that sleep-dependent memory consolidation may be impaired or occurs differently in older adults.Here, we give an overview of the mechanisms governing sleep-dependent memory consolidation, and the crucial points of this complex process that may dysfunction and result in impaired memory consolidation in aging.

  9. The influence of HIV infection on the age dependence of squamous ...

    African Journals Online (AJOL)

    diminishes with ageing, which may contribute to the age-related increase in cancer incidence. In the present analysis, the age dependence of squamous cell carcinoma of the skin (SCC) in the black African, coloured and white population groups of South. Africa (SA) was examined. The evidence that exposure to sunlight is ...

  10. Age-dependent Hepatic UDP-glucuronosyltransferase Gene Expression and Activity in Children

    Directory of Open Access Journals (Sweden)

    Elizabeth Neumann

    2016-11-01

    Full Text Available ABSTRACTUDP-glucuronosyltransferases (UGTs are important phase II drug metabolism enzymes. The aim of this study was to explore the relationship between age and changes in mRNA expression and activity of major human hepatic UGTs, as well as to understand the potential regulatory mechanism underlying this relationship. Using previously generated data, we investigated age-dependent mRNA expression levels of 11 hepatic UGTs (UGT1A1, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A9, UGT2B4, UGT2B7, UGT2B10, UGT2B15 and UGT2B17 and 16 transcription factors (AHR, AR, CAR, ESR2, FXR, GCCR, HNF1a, HNF3a, HNF3b, HNF4a, PPARA, PPARG, PPARGC, PXR, SP1, and STAT3 in liver tissue of donors (n = 38 ranging from 0 to 25 years of age. We also examined the correlation between age and microsomal activities using 14 known UGT drug substrates in the liver samples (n = 19 of children donors. We found a statistically significant increase (nominal p < 0.05 in the expression of UGT1A1, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT2B7 and UGT2B17, as well as glucuronidation activities of serotonin, testosterone, and vorinostat during the first 25 years of life. Expression of estrogen receptor 1 (ESR1 and pregnane X receptor (PXR, two strong UGT transcriptional regulators, were significantly correlated with both age and UGT mRNA expression (p ≤ 0.05. These results suggest that both UGT expression and activity increase during childhood and adolescence, possibly driven in part by hormonal signaling. Our findings may help explain inter-patient variability in response to medications among children.

  11. High Prevalence of Sinusitis in Children with Henoch-Schönlein Purpura

    Directory of Open Access Journals (Sweden)

    Haruna Nakaseko

    2011-01-01

    Full Text Available We evaluated the prevalence and the types of infectious foci in oral as well as ear, nose, and throat diseases, and we examined incidence of renal involvement with active treatment for focal infection in children with Henoch-Schönlein Purpura. A total of 96 children who presented at Aichi Children's Health and Medical Center and were diagnosed as having HSP were evaluated for infectious foci in the ear, nose, throat, and oral cavities. Seventy-one of 96 children (74.0% had some type of infectious lesion, such as sinusitis or tonsillitis, and the prevalence of sinusitis was the highest (51 cases, 53.7%. In 44 HSP patients without renal involvement at the first examination, the incidence of nephritis was lower (13.6% than in previous reports (17–54% due to our aggressive intervention for infectious foci.

  12. Age-dependent reliability model considering effects of maintenance and working conditions

    International Nuclear Information System (INIS)

    Martorell, Sebastian; Sanchez, Ana; Serradell, Vicente

    1999-01-01

    Nowadays, there is some doubt about building new nuclear power plants (NPPs). Instead, there is a growing interest in analyzing the possibility to extend current NPP operation, where life management programs play an important role. The evolution of the NPP safety depends on the evolution of the reliability of its safety components, which, in turn, is a function of their age along the NPP operational life. In this paper, a new age-dependent reliability model is presented, which includes parameters related to surveillance and maintenance effectiveness and working conditions of the equipment, both environmental and operational. This model may be used to support NPP life management and life extension programs, by improving or optimizing surveillance and maintenance tasks using risk and cost models based on such an age-dependent reliability model. The results of the sensitivity study in the example application show that the selection of the most appropriate maintenance strategy would directly depend on the previous parameters. Then, very important differences are expected to appear under certain circumstances, particularly, in comparison with other models that do not consider maintenance effectiveness and working conditions simultaneously

  13. Henoch–Schönlein purpura: a clinical case with dramatic presentation

    Science.gov (United States)

    Bento, João; Magalhães, Adriana; Moura, Conceição Souto; Hespanhol, Venceslau

    2010-01-01

    A case study involving a 55-year-old Caucasian male with end-stage glomerulosclerosis is presented here. Kidney biopsies showed no deposits on imunofluorescent microscopy. Relapsing massive haemoptysis and suspected bronchovascular malformation required lung lobectomy which revealed malformative and tortuous small blood vessels, with no vasculitis. Blood antinuclear antibodies, antineutrophil cytoplasmic antibodies and antiglomerular basement membrane antibodies were undetectable. Seric immunoglobulins and complement levels were normal. Three months later, arthralgia and joint oedema first appeared. Skin biopsy revealed vasculitis immune-reactive to immunoglobulin A. Systemic corticotherapy was then started. Two weeks later, the patient presented with abdominal pain melena and rectal bleeding (haematoquesia). Endoscopic study showed diffuse gastrointestinal haemorrhage. Angiographic study revealed diffuse lesions compatible with vasculitis and haemorrhage from multiple spots. Cyclophosphamide and then intravenous immunoglobulin were associated to treatment without response. Increasing blood loss occurred, with massive gastrointestinal haemorrhage and haemorrhagic ascitis. Death occurred due to uncontrolled diffuse bleeding. Necropsy findings showed generalised small vessels vasculitis compatible with Henoch–Schönlein purpura. PMID:22778211

  14. Severe Henoch-Schönlein purpura with infliximab for ulcerative colitis.

    Science.gov (United States)

    Song, Yang; Shi, Yan-Hong; He, Chong; Liu, Chang-Qin; Wang, Jun-Shan; Zhao, Yu-Jie; Guo, Yan-Min; Wu, Rui-Jin; Feng, Xiao-Yue; Liu, Zhan-Ju

    2015-05-21

    Infliximab (IFX) is an anti-tumor necrosis factor chimeric antibody that is effective for treatment of autoimmune disorders such as Crohn's disease and ulcerative colitis (UC). IFX is well tolerated with a low incidence of adverse effects such as infections, skin reactions, autoimmunity, and malignancy. Dermatological manifestations can appear as infusion reaction, vasculitis, cutaneous infections, psoriasis, eczema, and skin cancer. Here, we present an unusual case of extensive and sporadic subcutaneous ecchymosis in a 69-year-old woman with severe UC, partial colectomy and cecostomy, following her initial dose of IFX. The reaction occurred during infliximab infusion, and withdrawal of IFX led to gradual alleviation of her symptoms. We concluded that Henoch-Schönlein purpura, a kind of leukocytoclastic vasculitis, might have contributed to the development of the bruising. Although the precise mechanisms of the vasculitis are still controversial, such a case highlights the importance of subcutaneous adverse effects in the management of UC with IFX.

  15. A comprehensive approach to age-dependent dosimetric modeling

    International Nuclear Information System (INIS)

    Leggett, R.W.; Cristy, M.; Eckerman, K.F.

    1986-01-01

    In the absence of age-specific biokinetic models, current retention models of the International Commission on Radiological Protection (ICRP) frequently are used as a point of departure for evaluation of exposures to the general population. These models were designed and intended for estimation of long-term integrated doses to the adult worker. Their format and empirical basis preclude incorporation of much valuable physiological information and physiologically reasonable assumptions that could be used in characterizing the age-specific behavior of radioelements in humans. In this paper we discuss a comprehensive approach to age-dependent dosimetric modeling in which consideration is given not only to changes with age in masses and relative geometries of body organs and tissues but also to best available physiological and radiobiological information relating to the age-specific biobehavior of radionuclides. This approach is useful in obtaining more accurate estimates of long-term dose commitments as a function of age at intake, but it may be particularly valuable in establishing more accurate estimates of dose rate as a function of age. Age-specific dose rates are needed for a proper analysis of the potential effects on estimates or risk of elevated dose rates per unit intake in certain stages of life, elevated response per unit dose received during some stages of life, and age-specific non-radiogenic competing risks

  16. A comprehensive approach to age-dependent dosimetric modeling

    International Nuclear Information System (INIS)

    Leggett, R.W.; Cristy, M.; Eckerman, K.F.

    1987-01-01

    In the absence of age-specific biokinetic models, current retention models of the International Commission of Radiological Protection (ICRP) frequently are used as a point of departure for evaluation of exposures to the general population. These models were designed and intended for estimation of long-term integrated doses to the adult worker. Their format and empirical basis preclude incorporation of much valuable physiological information and physiologically reasonable assumptions that could be used in characterizing the age-specific behavior of radioelements in humans. In this paper a comprehensive approach to age-dependent dosimetric modeling is discussed in which consideration is given not only to changes with age in masses and relative geometries of body organs and tissues but also to best available physiological and radiobiological information relating to the age-specific biobehavior of radionuclides. This approach is useful in obtaining more accurate estimates of long-term dose commitments as a function of age at intake, but it may be particularly valuable in establishing more accurate estimates of dose rate as a function of age. Age-specific dose rates are needed for a proper analysis of the potential effects on estimates of risk of elevated dose rates per unit intake in certain stages of life, elevated response per unit dose received during some stages of life, and age-specific non-radiogenic competing risks. 16 refs.; 3 figs.; 1 table

  17. Modelling Anopheles gambiae s.s. Population Dynamics with Temperature- and Age-Dependent Survival

    Directory of Open Access Journals (Sweden)

    Céline Christiansen-Jucht

    2015-05-01

    Full Text Available Climate change and global warming are emerging as important threats to human health, particularly through the potential increase in vector- and water-borne diseases. Environmental variables are known to affect substantially the population dynamics and abundance of the poikilothermic vectors of disease, but the exact extent of this sensitivity is not well established. Focusing on malaria and its main vector in Africa, Anopheles gambiae sensu stricto, we present a set of novel mathematical models of climate-driven mosquito population dynamics motivated by experimental data suggesting that in An. gambiae, mortality is temperature and age dependent. We compared the performance of these models to that of a “standard” model ignoring age dependence. We used a longitudinal dataset of vector abundance over 36 months in sub-Saharan Africa for comparison between models that incorporate age dependence and one that does not, and observe that age-dependent models consistently fitted the data better than the reference model. This highlights that including age dependence in the vector component of mosquito-borne disease models may be important to predict more reliably disease transmission dynamics. Further data and studies are needed to enable improved fitting, leading to more accurate and informative model predictions for the An. gambiae malaria vector as well as for other disease vectors.

  18. E1A-dependent trans-activation of the human MYC promoter is mediated by the E2F factor

    International Nuclear Information System (INIS)

    Hiebert, S.W.; Lipp, M.; Nevins, J.R.

    1989-01-01

    E2F is a cellular transcription factor that binds to two sites in the adenovirus E2 promoter. Previous experiments have implicated E2F in the E1A-dependent transactivation of the E2 gene since levels of active E2F increase markedly during adenovirus infection in parallel with the increase in E2 transcription, and an E2F binding site can confer E1A inducibility to a heterologous promoter. Here the authors show that E2F binds to two sequence elements within the P2 promoter of the human MYC gene which are within a region that is critical for promoter activity. The MYC promoter can be trans-activated in an E1A-dependent manner and site-directed mutagenesis demonstrates that these E2F elements are essential for trans-activation. Finally, they also find that adenovirus infection of quiescent cells results in a stimulation of the endogenous MYC gene. They conclude that the activation of the E2F factor, which is likely responsible for the activation of viral E2 transcription, is also responsible for the E1A-dependent induction of MYC transcription

  19. Subclinical Hypothyroidism Is Independently Associated with Microalbuminuria in a Cohort of Prediabetic Egyptian Adults

    Directory of Open Access Journals (Sweden)

    Mervat M. El-Eshmawy

    2013-12-01

    Full Text Available BackgroundRecent evidence has suggested an association between subclinical hypothyroidism (SCH and microalbuminuria in patients with type 2 diabetes. However, whether SCH is related to microalbuminuria among subjects with prediabetes has not been studied. Thus, we evaluated the association between SCH and microalbuminuria in a cohort of prediabetic Egyptian adults.MethodsA total of 147 prediabetic subjects and 150 healthy controls matched for age and sex were enrolled in this study. Anthropometric measurements, plasma glucose, lipid profile, homeostasis model assessment of insulin resistance (HOMA-IR, thyroid stimulating hormone (TSH, free thyroxine, triiodothyronine levels, and urinary albumin-creatinine ratio (UACR were assessed.ResultsThe prevalence of SCH and microalbuminuria in the prediabetic subjects was higher than that in the healthy controls (16.3% vs. 4%, P<0.001; and 12.9% vs. 5.3%, P=0.02, respectively. Prediabetic subjects with SCH were characterized by significantly higher HOMA-IR, TSH levels, UACR, and prevalence of microalbuminuria than those with euthyroidism. TSH level was associated with total cholesterol (P=0.05, fasting insulin (P=0.01, HOMA-IR (P=0.01, and UACR (P=0.005. UACR was associated with waist circumference (P=0.01, fasting insulin (P=0.05, and HOMA-IR (P=0.02. With multiple logistic regression analysis, SCH was associated with microalbuminuria independent of confounding variables (β=2.59; P=0.01.ConclusionOur findings suggest that prediabetic subjects with SCH demonstrate higher prevalence of microalbuminuria than their non-SCH counterparts. SCH is also independently associated with microalbuminuria in prediabetic subjects. Screening and treatment for SCH may be warranted in those patients.

  20. Mixed models, linear dependency, and identification in age-period-cohort models.

    Science.gov (United States)

    O'Brien, Robert M

    2017-07-20

    This paper examines the identification problem in age-period-cohort models that use either linear or categorically coded ages, periods, and cohorts or combinations of these parameterizations. These models are not identified using the traditional fixed effect regression model approach because of a linear dependency between the ages, periods, and cohorts. However, these models can be identified if the researcher introduces a single just identifying constraint on the model coefficients. The problem with such constraints is that the results can differ substantially depending on the constraint chosen. Somewhat surprisingly, age-period-cohort models that specify one or more of ages and/or periods and/or cohorts as random effects are identified. This is the case without introducing an additional constraint. I label this identification as statistical model identification and show how statistical model identification comes about in mixed models and why which effects are treated as fixed and which are treated as random can substantially change the estimates of the age, period, and cohort effects. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  1. Mortality in Children Aged 0-9 Years: A Nationwide Cohort Study from Three Nordic Countries

    DEFF Research Database (Denmark)

    Yu, Yongfu; Qin, Guoyou; Cnattingius, Sven

    2016-01-01

    boys and girls decreased from 1.25 to 1.21 with the most prominent reduction in children aged 5–9 years (from 1.59 to 1.19). Neoplasms, diseases of the nervous system and transport accidents were the most frequent cause of death after the first year of life. These three leading causes of death declined...... comparing cause-specific mortality, and half of deaths from diseases of the nervous system occurred in infancy. Mortality rate due to transport accidents increased with age and was highest in boys aged 5–9 years. Conclusions Mortality rate in children aged 0–9 years has been decreasing with diminished...... difference between genders over the past decades. Our results suggest the importance of further research on mortality by causes of neoplasms, and causes of transport accidents—especially in children aged 5–9 years...

  2. I wonder if robots will take care of me when I am old: Positive aging representations of professionals working in health promotion services.

    Science.gov (United States)

    Craciun, Catrinel; Flick, Uwe

    2016-12-01

    How the social and institutional context is structured and represented by its actors has an impact on positive aging representations. This qualitative study explores professionals' views on positive aging, how they promote positive aging in their practice and what disparities occur between their discourses and the actual practice of promoting positive aging. Interviews were conducted with professionals from different active aging promotion services and analyzed with thematic coding. Findings show professionals hold negative views on aging while trying to promote positive views in their work, illustrating an existing theory-practice gap. Strategies used in practice can be integrated in existing agency models and inform interventions and active aging policies. © The Author(s) 2015.

  3. Modulation of NADP(+)-dependent isocitrate dehydrogenase in aging.

    Science.gov (United States)

    Kil, In Sup; Lee, Young Sup; Bae, Young Seuk; Huh, Tae Lin; Park, Jeen-Woo

    2004-01-01

    NADPH is an important cofactor in many biosynthesis pathways and the regeneration of reduced glutathione, critically important in cellular defense against oxidative damage. It is mainly produced by glucose-6-phosphate dehydrogenase, malic enzyme, and NADP(+)-specific isocitrate dehydrogenases (ICDHs). Here, we investigated age-related changes in ICDH activity and protein expression in IMR-90 human diploid fibroblast cells and tissues from Fischer 344 rats. We found that in IMR-90 cells the activity of cytosolic ICDH (IDPc) gradually increased with age up to the 46-48 population doubling level (PDL) and then gradually decreased at later PDL. 2',7'-Dichloro-fluorescein fluorescence which reflects intracellular ROS generation was increased with aging in IMR-90 cells. In ad libitum-fed rats, we noted age-related, tissue-specific modulations of IDPc and mitochondrial ICDH (IDPm) activities and protein expression in the liver, kidney and testes. In contrast, ICDH activities and protein expression were not significantly modulated in diet-restricted rats. These data suggest that modulation of ICDH is an age-dependent and a tissue-specific phenomenon.

  4. The role of HSP70 in mediating age-dependent mortality in sepsis

    Science.gov (United States)

    McConnell, Kevin W.; Fox, Amy C.; Clark, Andrew T.; Chang, Nai-Yuan Nicholas; Dominguez, Jessica A.; Farris, Alton B.; Buchman, Timothy G.; Hunt, Clayton R.; Coopersmith, Craig M.

    2011-01-01

    Sepsis is primarily a disease of the aged, with increased incidence and mortality occurring in aged hosts. Heat shock protein (HSP) 70 plays an important role in both healthy aging and the stress response to injury. The purpose of this study was to determine the role of HSP70 in mediating mortality and the host inflammatory response in aged septic hosts. Sepsis was induced in both young (6–12week old) and aged (16–17 month old) HSP70−/− and wild type (WT) mice to determine if HSP70 modulated outcome in an age-dependent fashion. Young HSP70−/− and WT mice subjected to cecal ligation and puncture (CLP), Pseudomonas aeruginosa pneumonia or Streptococcus pneumoniae pneumonia had no differences in mortality, suggesting HSP70 does not mediate survival in young septic hosts. In contrast, mortality was higher in aged HSP70−/− mice than aged WT mice subjected to CLP (p=0.01), suggesting HSP70 mediates mortality in sepsis in an age-dependent fashion. Compared to WT mice, aged septic HSP70−/− mice had increased gut epithelial apoptosis and pulmonary inflammation. In addition, HSP70−/−mice had increased systemic levels of TNF-α, IL-6, IL-10 and IL-1β compared to WT mice. These data demonstrate that HSP70 is a key determinant of mortality in aged but not young hosts in sepsis. HSP70 may play a protective role in an age-dependent response to sepsis by preventing excessive gut apoptosis and both pulmonary and systemic inflammation. PMID:21296977

  5. How does health-promoting lifestyle relate to sexual function among women of reproductive age in Iran?

    Science.gov (United States)

    Abedi, Parvin; Jorfi, Maryam; Afshari, Poorandokht; Fakhri, Ahmad

    2017-08-01

    This study aimed to evaluate the relation between health-promoting lifestyle and sexual function among women of reproductive age. In this cross-sectional study, 1200 women were recruited randomly from 10 public health centers in Ahvaz, Iran. A demographic questionnaire, Health Promoting Lifestyle Profile 2 (HPLP2), and Female Sexual Function Index (FSFI) were used for data collection. The inclusion criteria were as follows: women aged 15-45 years, married, monogamous, and having basic literacy. Data were analyzed using Kruskal-Wallis test, chi-square test, Spearman correlation coefficient, and logistic regression. All aspects of sexual function showed a significant relationship with different dimensions of HPLP2, except for pain and physical activity ( p function than other women (OR = 1.10, 95% CI: 1.06-1.14, p relations and stress management also showed a significant correlation with sexual function. Results of this study showed that health-promoting lifestyle dimensions are significantly related to all aspects of sexual function in women of reproductive age. Health policy makers should take lifestyle-related factors of reproductive-aged women into account when seeking to improve the sexual wellbeing of this population. Further attention should also be given to assessing the direction of causality.

  6. Chinese herbal medicine for the treatment of Henoch-Schönlein purpura nephritis in children: A prospective cohort study protocol.

    Science.gov (United States)

    Zhang, Jun; Lv, Jing; Pang, Shuang; Bai, Xiaohong; Yuan, Fang; Wu, Yubin; Jiang, Hong; Yang, Guanqi; Zhang, Shaoqing

    2018-06-01

    Henoch-Schönlein purpura nephritis (HSPN) involves the renal impairment of Henoch-Schönlein purpura and can easily relapse into life-threatening late nephropathy in severe cases. Although there is a lack of validated evidence for its effectiveness, Chinese herbal medicine (CHM) is one of the most commonly used methods in China to treat HSPN. It is thus need to report the protocol of a prospective cohort trial using CHM to investigate the effectiveness, safety and advantages for children with HSPN. This large, prospective, multicenter cohort study started in May 2015 in Shenyang. Six hundred children diagnosed with HSPN were recruited from 3 institutions and are followed-up every 2 to 4 weeks till May 2020. Detailed information of participants includes general information, history of treatment, physical examination, and symptoms of TCM is taken face-to-face at baseline. This study has received ethical approval from the ethics committee of institutional review board of the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine (No.2016CS(KT)-002-01). Articles summarizing the primary results and ancillary analyses will be published in peer-reviewed journals. Clinical Trials Registration: NCT02878018.

  7. Gis1 and Rph1 regulate glycerol and acetate metabolism in glucose depleted yeast cells.

    Directory of Open Access Journals (Sweden)

    Jakub Orzechowski Westholm

    Full Text Available Aging in organisms as diverse as yeast, nematodes, and mammals is delayed by caloric restriction, an effect mediated by the nutrient sensing TOR, RAS/cAMP, and AKT/Sch9 pathways. The transcription factor Gis1 functions downstream of these pathways in extending the lifespan of nutrient restricted yeast cells, but the mechanisms involved are still poorly understood. We have used gene expression microarrays to study the targets of Gis1 and the related protein Rph1 in different growth phases. Our results show that Gis1 and Rph1 act both as repressors and activators, on overlapping sets of genes as well as on distinct targets. Interestingly, both the activities and the target specificities of Gis1 and Rph1 depend on the growth phase. Thus, both proteins are associated with repression during exponential growth, targeting genes with STRE or PDS motifs in their promoters. After the diauxic shift, both become involved in activation, with Gis1 acting primarily on genes with PDS motifs, and Rph1 on genes with STRE motifs. Significantly, Gis1 and Rph1 control a number of genes involved in acetate and glycerol formation, metabolites that have been implicated in aging. Furthermore, several genes involved in acetyl-CoA metabolism are downregulated by Gis1.

  8. Practical applications of age-dependent reliability models and analysis of operational data

    Energy Technology Data Exchange (ETDEWEB)

    Lannoy, A.; Nitoi, M.; Backstrom, O.; Burgazzi, L.; Couallier, V.; Nikulin, M.; Derode, A.; Rodionov, A.; Atwood, C.; Fradet, F.; Antonov, A.; Berezhnoy, A.; Choi, S.Y.; Starr, F.; Dawson, J.; Palmen, H.; Clerjaud, L

    2005-07-01

    The purpose of the workshop was to present the experience of practical application of time-dependent reliability models. The program of the workshop comprises the following sessions: -) aging management and aging PSA (Probabilistic Safety Assessment), -) modeling, -) operation experience, and -) accelerating aging tests. In order to introduce time aging effect of particular component to the PSA model, it has been proposed to use the constant unavailability values on the short period of time (one year for example) calculated on the basis of age-dependent reliability models. As for modeling, it appears that the problem of too detailed statistical models for application is the lack of data for required parameters. As for operating experience, several methods of operating experience analysis have been presented (algorithms for reliability data elaboration and statistical identification of aging trend). As for accelerated aging tests, it is demonstrated that a combination of operating experience analysis with the results of accelerated aging tests of naturally aged equipment could provide a good basis for continuous operation of instrumentation and control systems.

  9. Practical applications of age-dependent reliability models and analysis of operational data

    International Nuclear Information System (INIS)

    Lannoy, A.; Nitoi, M.; Backstrom, O.; Burgazzi, L.; Couallier, V.; Nikulin, M.; Derode, A.; Rodionov, A.; Atwood, C.; Fradet, F.; Antonov, A.; Berezhnoy, A.; Choi, S.Y.; Starr, F.; Dawson, J.; Palmen, H.; Clerjaud, L.

    2005-01-01

    The purpose of the workshop was to present the experience of practical application of time-dependent reliability models. The program of the workshop comprises the following sessions: -) aging management and aging PSA (Probabilistic Safety Assessment), -) modeling, -) operation experience, and -) accelerating aging tests. In order to introduce time aging effect of particular component to the PSA model, it has been proposed to use the constant unavailability values on the short period of time (one year for example) calculated on the basis of age-dependent reliability models. As for modeling, it appears that the problem of too detailed statistical models for application is the lack of data for required parameters. As for operating experience, several methods of operating experience analysis have been presented (algorithms for reliability data elaboration and statistical identification of aging trend). As for accelerated aging tests, it is demonstrated that a combination of operating experience analysis with the results of accelerated aging tests of naturally aged equipment could provide a good basis for continuous operation of instrumentation and control systems

  10. Cell cycle age dependence for radiation-induced G2 arrest: evidence for time-dependent repair

    International Nuclear Information System (INIS)

    Rowley, R.

    1985-01-01

    Exponentially growing eucaryotic cells, irradiated in interphase, are delayed in progression to mitosis chiefly by arrest in G 2 . The sensitivity of Chinese hamster ovary cells to G 2 arrest induction by X rays increases through the cell cycle, up to the X-ray transition point (TP) in G 2 . This age response can be explained by cell cycle age-dependent changes in susceptibility of the target(s) for G 2 arrest and/or by changes in capability for postirradiation recovery from G 2 arrest damage. Discrimination between sensitivity changes and repair phenomena is possible only if the level of G 2 arrest-causing damage sustained by a cell at the time of irradiation and the level ultimately expressed as arrest can be determined. The ability of caffeine to ameliorate radiation-induced G 2 arrest, while inhibiting repair of G 2 arrest-causing damage makes such an analysis possible. In the presence of caffeine, progression of irradiated cells was relatively unperturbed, but on caffeine removal, G 2 arrest was expressed. The duration of G 2 arrest was independent of the length of the prior caffeine exposure. This finding indicates that the target for G 2 arrest induction is present throughout the cell cycle and that the level of G 2 arrest damage incurred is initially constant for all cell cycle phases. The data are consistent with the existence of a time-dependent recovery mechanism to explain the age dependence for radiation induction of G 2 arrest

  11. Analysis of a general age-dependent vaccination model for a vertically transmitted disease

    International Nuclear Information System (INIS)

    El Doma, M.

    1995-05-01

    A SIR epidemic model of a general age-dependent vaccination for a vertically as well as horizontally transmitted disease is investigated when the total population is time dependent, and fertility, mortality and removal rates depend on age. We establish the existence and the uniqueness of the solution and obtain the asymptotic behaviour for the solution. For the steady state solution a critical vaccination coverage which will eventually eradicate the disease is determined. (author). 18 refs

  12. Shorter preschool, leukocyte telomere length is associated with obesity at age 9 in Latino children

    DEFF Research Database (Denmark)

    Kjaer, Thora Wesenberg; Faurholt-Jepsen, D; Mehta, K M

    2018-01-01

    The aim of this study was to determine the potential role of leukocyte telomere length as a biomarker for development of childhood obesity in a low-income Latino population. A birth cohort of Latino children (N = 201) in San Francisco (recruited May 2006-May 2007) was followed until age 9...... and assessed annually for obesity and dietary intake. Leukocyte telomere length was measured at 4 and 5 years (n = 102) and assessed as a predictor for obesity at age 9, adjusting for known risk factors. Furthermore, leukocyte telomere length at age 4 and 5 was evaluated as a possible mediator...... of the relationship between excessive sugar-sweetened beverage consumption and obesity at age 9. Shorter leukocyte telomere length in preschoolers was associated with obesity at age 9 (adjusted odds ratio 0.35, 95% confidence interval 0.13-0.94) after adjustment for known risk factors. Telomere length mediated 11...

  13. Nox2-dependent ROS signaling protects against skeletal ageing

    Science.gov (United States)

    Bone remodeling is age-dependently regulated and changes dramatically during the course of development. Progressive accumulation of reactive oxygen species (ROS), including superoxide, hydrogen peroxide, and hydroxyl radicals, has been suspected to be the leading cause of many inflammatory and degen...

  14. EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria

    DEFF Research Database (Denmark)

    Ozen, Seza; Pistorio, Angela; Iusan, Silvia M

    2010-01-01

    To validate the previously proposed classification criteria for Henoch-Schönlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA)....

  15. Age-dependent changes in innate immune phenotype and function in rhesus macaques (Macaca mulatta

    Directory of Open Access Journals (Sweden)

    Mark Asquith

    2012-06-01

    Full Text Available Aged individuals are more susceptible to infections due to a general decline in immune function broadly referred to as immune senescence. While age-related changes in the adaptive immune system are well documented, aging of the innate immune system remains less well understood, particularly in nonhuman primates. A more robust understanding of age-related changes in innate immune function would provide mechanistic insight into the increased susceptibility of the elderly to infection. Rhesus macaques have proved a critical translational model for aging research, and present a unique opportunity to dissect age-dependent modulation of the innate immune system. We examined age-related changes in: (i innate immune cell frequencies; (ii expression of pattern recognition receptors (PRRs and innate signaling molecules; (iii cytokine responses of monocytes and dendritic cells (DC following stimulation with PRR agonists; and (iv plasma cytokine levels in this model. We found marked changes in both the phenotype and function of innate immune cells. This included an age-associated increased frequency of myeloid DC (mDC. Moreover, we found toll-like receptor (TLR agonists lipopolysaccharide (TLR4, fibroblast stimulating ligand-1 (TLR2/6, and ODN2006 (TLR7/9 induced reduced cytokine responses in aged mDC. Interestingly, with the exception of the monocyte-derived TNFα response to LPS, which increased with age, TNFα, IL-6, and IFNα responses declined with age. We also found that TLR4, TLR5, and innate negative regulator, sterile alpha and TIR motif containing protein (SARM, were all expressed at lower levels in young animals. By contrast, absent in melanoma 2 and retinoic acid-inducible gene I expression was lowest in aged animals. Together, these observations indicate that several parameters of innate immunity are significantly modulated by age and contribute to differential immune function in aged macaques.

  16. Intergenerational service learning: to promote active aging, and occupational therapy gerontology practice.

    Science.gov (United States)

    Horowitz, Beverly P; Wong, Stephanie Dapice; Dechello, Karen

    2010-01-01

    Americans are living longer, and the meaning of age has changed, particularly for Boomers and seniors. These demographic changes have economic and social ramifications with implications for health care, including rehabilitation services, and health science education. Service learning is an experiential learning pedagogy that integrates traditional higher education with structured active learning experiences. This article reports on one intergenerational service learning program spanning 3 years. It was designed to facilitate community dialogue on fall prevention and active aging, and to provide intergenerational educational community-based experiences in occupational therapy professional education. The program additionally sought to promote students' understanding of aging and issues related to aging in place, students' professional development and civic engagement, and to encourage students to consider pursuing a career in occupational therapy gerontology practice.

  17. An NF-Y-dependent switch of positive and negative histone methyl marks on CCAAT promoters.

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    Giacomo Donati

    Full Text Available BACKGROUND: Histone tails have a plethora of different post-translational modifications, which are located differently in "open" and "closed" parts of genomes. H3K4me3/H3K79me2 and H4K20me3 are among the histone marks associated with the early establishment of active and inactive chromatin, respectively. One of the most widespread promoter elements is the CCAAT box, bound by the NF-Y trimer. Two of NF-Y subunits have an H2A-H2B-like structure. PRINCIPAL FINDINGS: We established the causal relationship between NF-Y binding and positioning of methyl marks, by ChIP analysis of mouse and human cells infected with a dominant negative NF-YA: a parallel decrease in NF-Y binding, H3K4me3, H3K79me2 and transcription was observed in promoters that are dependent upon NF-Y. On the contrary, changes in the levels of H3K9-14ac were more subtle. Components of the H3K4 methylating MLL complex are not recruited in the absence of NF-Y. As for repressed promoters, NF-Y removal leads to a decrease in the H4K20me3 mark and deposition of H3K4me3. CONCLUSIONS: Two relevant findings are reported: (i NF-Y gains access to its genomic locations independently from the presence of methyl histone marks, either positive or negative; (ii NF-Y binding has profound positive or negative consequences on the deposition of histone methyl marks. Therefore NF-Y is a fundamental switch at the heart of decision between gene activation and repression in CCAAT regulated genes.

  18. Relevance in print of law of administrative regulations according to paragraph 48 BImSchG in the licensing procedure

    International Nuclear Information System (INIS)

    Breuer, R.

    1978-01-01

    The author discusses in great detail the legal problem of administrative regulations according to paragraph 48 of the Bundes-Immissionsschutzgesetz, BImSchG (Federal Act for the prevention of immissions) and their relevance in point of law in licensing procedures. He very carefully and skilfully presents the different opinions stated in the precedents and by the body of doctrine and quite convincingly explains why he rejects the doctrine of allowing the administration some latitude in their judgement, and thus the doctrine of the defensible opinion with regard to the examination by the court of undefined legal terms. According to the auther's view, the administrative regulations should be regarded as anticipated expert opinions because of the way they are drawn up and because of the way the relevant committees setting up the rules are constituted, i.e. they can serve as a basis for judical decisions. In this connection the author points out that in any case it is left to the court's decisions whether a non-formal expert opinion is deemed to be sufficient, or whether the rules of procedure require a formal expert opinion. Furthermore, several ways of enhancing the binding effect of the administrative regulations pursuant to paragraph 48 of the BImSchG by means of legislatory measures are shown. (UN) [de

  19. Coverage dependent desorption dynamics of deuterium on Si(100) surfaces: interpretation with a diffusion-promoted desorption model.

    Science.gov (United States)

    Matsuno, T; Niida, T; Tsurumaki, H; Namiki, A

    2005-01-08

    We studied coverage dependence of time-of-flight (TOF) spectra of D2 molecules thermally desorbed from the D/Si(100) surface. The mean translational energies Et of desorbed D2 molecules were found to increase from 0.20+/-0.05 eV to 0.40+/-0.04 eV as the desorption coverage window was decreased from 1.0 ML> or =thetaD> or =0.9 ML to 0.2 ML> or =thetaD> or =0 ML, being consistent with the kinetics switch predicted in the interdimer mechanism. The measured TOF spectra were deconvoluted into 2H, 3H, and 4H components by a curve fitting method along the principle of detailed balance. As a result, it turned out that the desorption kinetics changes from the 4H to the 3H situation at high coverage above thetaD=0.9 ML, while the 2H desorption is dominant for a quite wide coverage region up to thetaD=0.8 ML. A dynamic desorption mechanism by which the desorption is promoted by D-atom diffusion to dangling bonds was proposed. 2005 American Institute of Physics.

  20. Hyperprolactinemia in Children with Subclinical Hypothyroidism.

    Science.gov (United States)

    Sharma, Neera; Dutta, Deep; Sharma, Lokesh Kumar

    2017-12-15

    Prevalence of hyperprolactinemia in children with subclinical hypothyroidism (ScH) is not known. This study aimed to determine the occurrence and predictors of hyperprolactinemia in euthyroid children and in children with ScH and overt primary hypothyroidism (OPH). Serum prolactin levels were estimated in consecutive children hypothyroidism, multiple pituitary hormone deficiency, comorbid states, and drug-induced hyperprolactinemia were excluded. From the initially screened 791 children, hormonal data from 602 children who fulfilled all criteria were analyzed. Seventy-one (11.79%) of these had ScH, and 33 (5.48%) had OPH. Occurrence of hyperprolactinemia was highest in the OPH group (51.51%), followed by ScH (30.98%) and euthyroid children (4.41%) (p<0.001). Median (25 th -75 th percentiles) levels for prolactin in euthyroid, ScH, and OPH children were 13.3 (9.4-17.95), 19.15 (15.97-30.12), and 28.86 (17.05-51.9) ng/mL, respectively (p<0.001). In children, prolactin levels were comparable in males and females. An age-related increase in serum prolactin was noted in euthyroid children, which was statistically significant in post-pubertal (16-18 years) children. Area under the curve for thyroid stimulating hormone (TSH) in predicting hyperprolactinemia in children was 0.758 (95% confidence interval: 0.673-0.829; p<0.001). TSH ≥4.00 mIU/L had a sensitivity of 69.4% and specificity of 77.6% in detecting hyperprolactinemia. Hyperprolactinemia is common in children with ScH and OPH. TSH ≥4.00 mIU/L has a good sensitivity and specificity in predicting hyperprolactinemia in children. More studies are needed to establish if hyperprolactinemia should be an indication for treating ScH in children.

  1. Depth-dependent variations in Achilles tendon deformations with age are associated with reduced plantarflexor performance during walking

    Science.gov (United States)

    Thelen, Darryl G.

    2015-01-01

    The anatomical arrangement of the Achilles tendon (AT), with distinct fascicle bundles arising from the gastrocnemius and soleus muscles, may facilitate relatively independent behavior of the triceps surae muscles. A reduced capacity for sliding between adjacent tendon fascicles with age may couple gastrocnemius and soleus muscle behavior, thereby potentially contributing to diminished plantarflexor performance commonly observed in old adults. Nine healthy young (mean age, 23.9 yr) and eight healthy old (69.9 yr) adults walked at three speeds (0.75, 1.00, and 1.25 m/s) on a force-sensing treadmill. We coupled dynamic ultrasound imaging of the free AT with motion capture and inverse dynamic analyses to compute, in part: 1) depth-dependent variations in AT tissue displacements and elongations and 2) net ankle joint kinetics during push-off. The difference in displacements between superficial and deep AT regions, and in their corresponding elongations, did not differ between old and young adults at the slower two walking speeds (P > 0.61). However, old adults walked with 41% smaller depth-dependent variations in free AT displacements and elongations at 1.25 m/s (P = 0.02). These more uniform tendon deformations in old adults most strongly correlated with reduced peak ankle moment (R2 = 0.40), but also significantly correlated with reduced peak power generation (R2 = 0.15) and positive ankle work during push-off (R2 = 0.19) (P > 0.01). Our findings: 1) demonstrate a potential role for nonuniform AT deformations in governing gastrocnemius and soleus muscle-tendon function and 2) allude to altered tendon behavior that may contribute to the age-related reduction in plantarflexor performance during walking. PMID:26023223

  2. Health, lifestyle and gender influences on aging well: An Australian longitudinal analysis to guide health promotion

    Directory of Open Access Journals (Sweden)

    Hal eKendig

    2014-07-01

    Full Text Available A primary societal goal for aging is enabling older people to continue to live well as long as possible. The evidence base around aging well (‘healthy’, ‘active’ and ‘successful’ aging has been constructed mainly from academic and professional conceptualizations of mortality, morbidity, functioning, and psychological well-being with some attention to lay views. Our study aims to inform action on health promotion to achieve aging well as conceptualized by qualitative research identifying what older Australians themselves value most: continuing to live as long as possible in the community with independence in daily living, and good self-rated health and psychological well-being. Multivariate survival analyses from the Melbourne Longitudinal Studies on Healthy Ageing (MELSHA program found that important threats to aging well for the total sample over a 12 year period were chronological age, multi-morbidity, low perceived social support, low nutritional score, and being underweight. For men, threats to aging well were low strain, perceived inadequacy of social activity, and being a current smoker. For women, urinary incontinence, low physical activity and being underweight were threats to aging well. The findings indicate that healthy lifestyles can assist aging well, and suggest the value of taking gender into account in health promotion strategies.

  3. Health, lifestyle, and gender influences on aging well: an Australian longitudinal analysis to guide health promotion.

    Science.gov (United States)

    Kendig, Hal; Browning, Colette J; Thomas, Shane A; Wells, Yvonne

    2014-01-01

    A primary societal goal for aging is enabling older people to continue to live well as long as possible. The evidence base around aging well ("healthy," "active," and "successful" aging) has been constructed mainly from academic and professional conceptualizations of mortality, morbidity, functioning, and psychological well-being with some attention to lay views. Our study aims to inform action on health promotion to achieve aging well as conceptualized by qualitative research identifying what older Australians themselves value most: continuing to live as long as possible in the community with independence in daily living, and good self-rated health and psychological well-being. Multivariate survival analyses from the Melbourne longitudinal studies on healthy aging program found that important threats to aging well for the total sample over a 12-year period were chronological age, multi-morbidity, low perceived social support, low nutritional score, and being under-weight. For men, threats to aging well were low strain, perceived inadequacy of social activity, and being a current smoker. For women, urinary incontinence, low physical activity and being under-weight were threats to aging well. The findings indicate that healthy lifestyles can assist aging well, and suggest the value of taking gender into account in health promotion strategies.

  4. A Role of Sp1 Binding Motifs in Basal and Large T-Antigen-Induced Promoter Activities of Human Polyomavirus HPyV9 and Its Variant UF-1

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    Ugo Moens

    2017-11-01

    Full Text Available Human polyomavirus 9 (HPyV9 was originally detected in the serum of a renal transplant patient. Seroepidemiological studies showed that ~20–50% of the human population have antibodies against this virus. HPyV9 has not yet been associated with any disease and little is known about the route of infection, transmission, host cell tropism, and genomic variability in circulating strains. Recently, the HPyV9 variant UF-1 with an eight base-pair deletion, a thirteen base-pair insertion and with point mutations, creating three putative Sp1 binding sites in the late promoter was isolated from an AIDS patient. Transient transfection studies with a luciferase reporter plasmid driven by HPyV9 or UF1 promoter demonstrated that UF1 early and late promoters were stronger than HPyV9 promoters in most cell lines, and that the UF1 late promoter was more potently activated by HPyV9 large T-antigen (LTAg. Mutation of two Sp1 motifs strongly reduced trans-activation of the late UF1 promoter by HPyV9 LTAg in HeLa cells. In conclusion, the mutations in the UF1 late promoter seem to strengthen its activity and its response to stimulation by HPyV9 LTAg in certain cells. It remains to be investigated whether these promoter changes have an influence on virus replication and affect the possible pathogenic properties of the virus.

  5. Mouse Rad9b is essential for embryonic development and promotes resistance to DNA damage

    Science.gov (United States)

    Leloup, Corinne; Hopkins, Kevin M.; Wang, Xiangyuan; Zhu, Aiping; Wolgemuth, Debra J.; Lieberman, Howard B.

    2010-01-01

    RAD9 participates in promoting resistance to DNA damage, cell cycle checkpoint control, DNA repair, apoptosis, embryogenesis, and regulation of transcription. A paralogue of RAD9 (named RAD9B) has been identified. To define the function of mouse Rad9b (Mrad9b), embryonic stem (ES) cells with a targeted gene deletion were constructed and used to generate Mrad9b mutant mice. Mrad9b−/− embryos are resorbed after E7.5 while some of the heterozygotes die between E12.5 and a few days after birth. Mrad9b is expressed in embryonic brain and Mrad9b+/− embryos exhibit abnormal neural tube closure. Mrad9b−/− mouse embryonic fibroblasts are not viable. Mrad9b−/− ES cells are more sensitive to gamma rays and mitomycin C than Mrad9b+/+ controls, but show normal gamma-ray-induced G2/M checkpoint control. There is no evidence of spontaneous genomic instability in Mrad9b−/− cells. Our findings thus indicate that Mrad9b is essential for embryonic development and mediates resistance to certain DNA damaging agents. PMID:20842695

  6. Transformation of Au144(SCH2CH2Ph)60 to Au133(SPh-tBu)52 Nanomolecules: Theoretical and Experimental Study.

    Science.gov (United States)

    Nimmala, Praneeth Reddy; Theivendran, Shevanuja; Barcaro, Giovanni; Sementa, Luca; Kumara, Chanaka; Jupally, Vijay Reddy; Apra, Edoardo; Stener, Mauro; Fortunelli, Alessandro; Dass, Amala

    2015-06-04

    Ultrastable gold nanomolecule Au144(SCH2CH2Ph)60 upon etching with excess tert-butylbenzenethiol undergoes a core-size conversion and compositional change to form an entirely new core of Au133(SPh-tBu)52. This conversion was studied using high-resolution electrospray mass spectrometry which shows that the core size conversion is initiated after 22 ligand exchanges, suggesting a relatively high stability of the Au144(SCH2CH2Ph)38(SPh-tBu)22 intermediate. The Au144 → Au133 core size conversion is surprisingly different from the Au144 → Au99 core conversion reported in the case of thiophenol, -SPh. Theoretical analysis and ab initio molecular dynamics simulations show that rigid p-tBu groups play a crucial role by reducing the cluster structural freedom, and protecting the cluster from adsorption of exogenous and reactive species, thus rationalizing the kinetic factors that stabilize the Au133 core size. This 144-atom to 133-atom nanomolecule's compositional change is reflected in optical spectroscopy and electrochemistry.

  7. Age- and sex-dependent model for estimating radioiodine dose to a normal thyroid

    International Nuclear Information System (INIS)

    Killough, G.G.; Eckerman, K.F.

    1985-01-01

    This paper describes the derivation of an age- and sex-dependent model of radioiodine dosimetry in the thyroid and the application of the model to estimating the thyroid dose for each of 4215 patients who were exposed to 131 I in diagnostic and therapeutic procedures. The model was made to conform to these data requirements by the use of age-specific estimates of the biological half-time of iodine in the thyroid and an age- and sex-dependent representation of the mass of the thyroid. Also, it was assumed that the thyroid burden was maximum 24 hours after administration (the 131 I dose is not critically sensitive to this assumption). The metabolic model is of the form A(t) = K[exp(-μ 1 t) - exp(-μ 2 t)] (μCi), where μ 1 = lambda/sub r/ + lambda/sub i//sup b/ (i = 1, 2), lambda/sub r/ is the radiological decay-rate coefficient, and lambda/sub i//sup b/ are biological removal rate coefficients. The values of lambda/sub i//sup b/ are determined by solving a nonlinear equation that depends on assumptions about the time of maximum uptake and the eventual biological loss rate (through which age dependence enters). The value of K may then be calculated from knowledge of the uptake at a particular time. The dosimetric S-factor (rad/μCi-day) is based on specific absorbed fractions for photons of energy ranging from 0.01 to 4.0 MeV for thyroid masses from 1.29 to 19.6 g; the functional form of the S-factor also involves the thyroid mass explicitly, through which the dependence on age and sex enters. An analysis of sensitivity of the model to uncertainties in the thyroid mass and the biological removal rate for several age groups is reported. The model could prove useful in the dosimetry of very short-lived radioiodines. Tables of age- and sex-dependent coefficients are provided to enable readers to make their own calculations. 12 refs., 5 figs., 4 tabs

  8. Bmi-1 promotes the aggressiveness of glioma via activating the NF-kappaB/MMP-9 signaling pathway

    International Nuclear Information System (INIS)

    Jiang, Lili; Wu, Jueheng; Yang, Yi; Liu, Liping; Song, Libing; Li, Jun; Li, Mengfeng

    2012-01-01

    The prognosis of human glioma is poor, and the highly invasive nature of the disease represents a major impediment to current therapeutic modalities. The oncoprotein B-cell-specific Moloney murine leukemia virus integration site 1 protein (Bmi-1) has been linked to the development and progression of glioma; however, the biological role of Bmi-1 in the invasion of glioma remains unclear. A172 and LN229 glioma cells were engineered to overexpress Bmi-1 via stable transfection or to be silenced for Bmi-1 expression using RNA interfering method. Migration and invasiveness of the engineered cells were assessed using wound healing assay, Transwell migration assay, Transwell matrix penetration assay and 3-D spheroid invasion assay. MMP-9 expression and activity were measured using real-time PCR, ELISA and the gelatin zymography methods. Expression of NF-kappaB target genes was quantified using real-time PCR. NF-kappaB transcriptional activity was assessed using an NF-kappaB luciferase reporter system. Expression of Bmi-1 and MMP-9 in clinical specimens was analyzed using immunohistochemical assay. Ectopic overexpression of Bmi-1 dramatically increased, whereas knockdown of endogenous Bmi-1 reduced, the invasiveness and migration of glioma cells. NF-kappaB transcriptional activity and MMP-9 expression and activity were significantly increased in Bmi-1-overexpressing but reduced in Bmi-1-silenced cells. The reporter luciferase activity driven by MMP-9 promoter in Bmi-1-overexpressing cells was dependent on the presence of a functional NF-kappaB binding site, and blockade of NF-kappaB signaling inhibited the upregulation of MMP-9 in Bmi-1 overexpressing cells. Furthermore, expression of Bmi-1 correlated with NF-kappaB nuclear translocation as well as MMP-9 expression in clinical glioma samples. Bmi-1 may play an important role in the development of aggressive phenotype of glioma via activating the NF-kappaB/MMP-9 pathway and therefore might represent a novel therapeutic

  9. Bmi-1 promotes the aggressiveness of glioma via activating the NF-kappaB/MMP-9 signaling pathway

    Directory of Open Access Journals (Sweden)

    Jiang Lili

    2012-09-01

    Full Text Available Abstract Background The prognosis of human glioma is poor, and the highly invasive nature of the disease represents a major impediment to current therapeutic modalities. The oncoprotein B-cell-specific Moloney murine leukemia virus integration site 1 protein (Bmi-1 has been linked to the development and progression of glioma; however, the biological role of Bmi-1 in the invasion of glioma remains unclear. Methods A172 and LN229 glioma cells were engineered to overexpress Bmi-1 via stable transfection or to be silenced for Bmi-1 expression using RNA interfering method. Migration and invasiveness of the engineered cells were assessed using wound healing assay, Transwell migration assay, Transwell matrix penetration assay and 3-D spheroid invasion assay. MMP-9 expression and activity were measured using real-time PCR, ELISA and the gelatin zymography methods. Expression of NF-kappaB target genes was quantified using real-time PCR. NF-kappaB transcriptional activity was assessed using an NF-kappaB luciferase reporter system. Expression of Bmi-1 and MMP-9 in clinical specimens was analyzed using immunohistochemical assay. Results Ectopic overexpression of Bmi-1 dramatically increased, whereas knockdown of endogenous Bmi-1 reduced, the invasiveness and migration of glioma cells. NF-kappaB transcriptional activity and MMP-9 expression and activity were significantly increased in Bmi-1-overexpressing but reduced in Bmi-1-silenced cells. The reporter luciferase activity driven by MMP-9 promoter in Bmi-1-overexpressing cells was dependent on the presence of a functional NF-kappaB binding site, and blockade of NF-kappaB signaling inhibited the upregulation of MMP-9 in Bmi-1 overexpressing cells. Furthermore, expression of Bmi-1 correlated with NF-kappaB nuclear translocation as well as MMP-9 expression in clinical glioma samples. Conclusions Bmi-1 may play an important role in the development of aggressive phenotype of glioma via activating the NF

  10. Atherogenic Lipoproteins in Subclinical Hypothyroidism and Their Relationship with Hepatic Lipase Activity: Response to Replacement Treatment with Levothyroxine.

    Science.gov (United States)

    Brenta, Gabriela; Berg, Gabriela; Miksztowicz, Veronica; Lopez, Graciela; Lucero, Diego; Faingold, Cristina; Murakami, Masami; Machima, Tetsudo; Nakajima, Katsuyuki; Schreier, Laura

    2016-03-01

    Qualitative lipoprotein changes, such as an increase in fasting remnants, are reported in subclinical hypothyroidism (SCH). It was hypothesized that such changes are due to reduced hepatic lipase (HL) activity in SCH: HL is an enzyme regulated by thyroid hormones, and is involved in the degradation of triglyceride (TG)-rich remnants. This study aimed to quantify remnant-like lipoproteins (RLP), small dense LDL (sdLDL), and HL activity in women with SCH, and to assess these parameters after levothyroxine replacement therapy. This was an observational cross-sectional study with a subsequent longitudinal follow-up. Findings in women with thyrotropin levels >4.5 mIU/L (SH group) were compared with age- and body mass index (BMI)-matched euthyroid women (control group). In addition, a subgroup analysis was undertaken in SCH women who chose to receive levothyroxine treatment (0.9 μg/kg/day) for 6 months. RLP was quantified by measuring cholesterol (RLP-C) and triglycerides (RLP-TG) after immunoaffinity chromatography, and sdLDL by automated standardized methods; HL activity was measured in post-heparin plasma. The SCH group included 37 women; 29 women were included in the control group. In addition, 22 women with SCH were included in the subgroup analysis (levothyroxine treatment). Significantly higher RLP values were observed in the SCH group than in the control group: RLP-C (median [range], mg/dL): 20.3 (5.8-66.8) versus 10.2 (2.7-36.3), p = 0.005; RLP-TG (mg/dL): 26.3 (3.2-123.3) versus 12.1 (2.5-61.6), p = 0.033. HL activity (mean ± standard deviation [SD], μmol free fatty acid/mL post-heparin plasma.h)-9.83 ± 4.25 versus 9.92 ± 5.20, p = 0.707-and sdLDL levels (mg/dL)-23.1 ± 10.7 versus 22.6 ± 8.4, p = 0.83-were similar. After levothyroxine, RLP-C decreased-21.5 (5.8-66.8) versus 17.2 (4.1-45.6), p = 0.023-and HL increased-9.75 ± 4.04 versus 11.86 ± 4.58, p = 0.012-in the subgroup of SCH women. No changes

  11. Experimental appraisal of personal beliefs in science: constraints on performance in the 9 to 14 age group.

    Science.gov (United States)

    Howe, C; Tolmie, A; Sofroniou, N

    1999-06-01

    Recent curricula initiatives have promoted experimentation as a means by which relatively young children can appraise their personal beliefs and thereby modify these beliefs towards received scientific ideas. However, key psychological theories signal problems, and the enterprise is not in any event securely grounded in empirical research. As a consequence, the study reported here aimed to provide comprehensive information about children's abilities to use experimentation to appraise their beliefs, while allowing full exploration of theorized constraints. The study involved 24 children at each of three age levels within the 9 to 14 range. The children were first interviewed to establish their beliefs about influences on outcome in four educationally significant topic areas: flotation, pressure, motion and shadows. Subsequently, they were asked to conduct investigations to determine whether selected beliefs were correct. The results showed that, regardless of age or topic, very few children appreciated that to explore whether some variable is influencing outcome it is necessary to manipulate that variable experimentally and that variable only. There was a strong tendency to manipulate other variables, a tendency attributed to the intrusion of everyday reasoning practices into the experimental context. Once extraneous variables had been introduced, the children experienced great difficulties with subsequent stages in the experimental process, e.g., predicting, observing and drawing conclusions. It is concluded that experimentation as a means of appraising beliefs is not straightforward in the 9 to 14 age group, and that the pattern of difficulties has psychological significance given the background theories. Nevertheless, while not straightforward, experimental appraisal remains possible given appropriate teacher support, and proposals are made as to the form which the support should take.

  12. Fatigue Resistance of GX12CrMoVNbN9-1 Cast Steel after Ageing Process

    Directory of Open Access Journals (Sweden)

    Stanisław MROZIŃSKI

    2014-12-01

    Full Text Available In the present paper, low cycle fatigue behaviour of GX12CrMoVNbN9-1 (GP91 cast steel is presented. Fatigue tests were performed under isothermal conditions at room temperature and at 550 and 600oC, on five levels of total strain amplitude value ɛac = 0.25÷0.60%. The cast steel subject to investigation was in the as-received condition (after heat treatment and after 8000 hours of ageing at the temperature of 600oC. Performed research has shown an insignificant influence of the ageing process on mechanical properties of GP91 cast steel, determined with the static test of tension. Analysis of the performed tests has proved that GP91 cast steel in the as-received condition and after ageing process was characterized by strong cyclic softening without a clear period of stabilization of the hysteresis loop parameters. The fatigue lifetime curves at each temperature were obtained based on Basquin and Coffin – Manson equations. The process of ageing of GP91 cast steel contributed to a decrease in its fatigue life Nf from a few to a few dozen percent, and the level of fatigue life was dependent on the value of strain amplitude ɛac. It has also been stated that the fatigue life Nf of GP91 cast steel is determined by its plastic properties, and the degree of changes in fatigue life Nf was dependent not only on the temperature of testing, but also on the value of strain amplitude ɛac. DOI: http://dx.doi.org/10.5755/j01.ms.20.4.6077

  13. 25-Hydroxycholesterol promotes fibroblast-mediated tissue remodeling through NF-κB dependent pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ichikawa, Tomohiro [Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, 811-1 Kimiidera, Wakayama 641-8509 (Japan); Sugiura, Hisatoshi, E-mail: sugiura@rm.med.tohoku.ac.jp [Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574 (Japan); Koarai, Akira; Kikuchi, Takashi; Hiramatsu, Masataka; Kawabata, Hiroki; Akamatsu, Keiichiro; Hirano, Tsunahiko; Nakanishi, Masanori; Matsunaga, Kazuto; Minakata, Yoshiaki [Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, 811-1 Kimiidera, Wakayama 641-8509 (Japan); Ichinose, Masakazu [Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574 (Japan)

    2013-05-01

    Abnormal structural alterations termed remodeling, including fibrosis and alveolar wall destruction, are important features of the pathophysiology of chronic airway diseases such as chronic obstructive pulmonary disease (COPD) and asthma. 25-hydroxycholesterol (25-HC) is enzymatically produced by cholesterol 25-hydorxylase (CH25H) in macrophages and is reported to be involved in the formation of arteriosclerosis. We previously demonstrated that the expression of CH25H and production of 25HC were increased in the lungs of COPD. However, the role of 25-HC in lung tissue remodeling is unknown. In this study, we investigated the effect of 25-HC on fibroblast-mediated tissue remodeling using human fetal lung fibroblasts (HFL-1) in vitro. 25-HC significantly augmented α-smooth muscle actin (SMA) (P<0.001) and collagen I (P<0.001) expression in HFL-1. 25-HC also significantly enhanced the release and activation of matrix metallaoproteinase (MMP)-2 (P<0.001) and MMP-9 (P<0.001) without any significant effect on the production of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. 25-HC stimulated transforming growth factor (TGF)-β{sub 1} production (P<0.01) and a neutralizing anti-TGF-β antibody restored these 25-HC-augmented pro-fibrotic responses. 25-HC significantly promoted the translocation of nuclear factor (NF)-κB p65 into the nuclei (P<0.01), but not phospholylated-c-jun, a complex of activator protein-1. Pharmacological inhibition of NF-κB restored the 25-HC-augmented pro-fibrotic responses and TGF-β{sub 1} release. These results suggest that 25-HC could contribute to fibroblast-mediated lung tissue remodeling by promoting myofibroblast differentiation and the excessive release of extracellular matrix protein and MMPs via an NF-κB-TGF-β dependent pathway.

  14. Association with Aurora-A Controls N-MYC-Dependent Promoter Escape and Pause Release of RNA Polymerase II during the Cell Cycle

    Directory of Open Access Journals (Sweden)

    Gabriele Büchel

    2017-12-01

    Full Text Available MYC proteins bind globally to active promoters and promote transcriptional elongation by RNA polymerase II (Pol II. To identify effector proteins that mediate this function, we performed mass spectrometry on N-MYC complexes in neuroblastoma cells. The analysis shows that N-MYC forms complexes with TFIIIC, TOP2A, and RAD21, a subunit of cohesin. N-MYC and TFIIIC bind to overlapping sites in thousands of Pol II promoters and intergenic regions. TFIIIC promotes association of RAD21 with N-MYC target sites and is required for N-MYC-dependent promoter escape and pause release of Pol II. Aurora-A competes with binding of TFIIIC and RAD21 to N-MYC in vitro and antagonizes association of TOP2A, TFIIIC, and RAD21 with N-MYC during S phase, blocking N-MYC-dependent release of Pol II from the promoter. Inhibition of Aurora-A in S phase restores RAD21 and TFIIIC binding to chromatin and partially restores N-MYC-dependent transcriptional elongation. We propose that complex formation with Aurora-A controls N-MYC function during the cell cycle.

  15. Age-dependent change of HMGB1 and DNA double-strand break accumulation in mouse brain

    International Nuclear Information System (INIS)

    Enokido, Yasushi; Yoshitake, Ayaka; Ito, Hikaru; Okazawa, Hitoshi

    2008-01-01

    HMGB1 is an evolutionarily conserved non-histone chromatin-associated protein with key roles in maintenance of nuclear homeostasis; however, the function of HMGB1 in the brain remains largely unknown. Recently, we found that the reduction of nuclear HMGB1 protein level in the nucleus associates with DNA double-strand break (DDSB)-mediated neuronal damage in Huntington's disease [M.L. Qi, K. Tagawa, Y. Enokido, N. Yoshimura, Y. Wada, K. Watase, S. Ishiura, I. Kanazawa, J. Botas, M. Saitoe, E.E. Wanker, H. Okazawa, Proteome analysis of soluble nuclear proteins reveals that HMGB1/2 suppress genotoxic stress in polyglutamine diseases, Nat. Cell Biol. 9 (2007) 402-414]. In this study, we analyze the region- and cell type-specific changes of HMGB1 and DDSB accumulation during the aging of mouse brain. HMGB1 is localized in the nuclei of neurons and astrocytes, and the protein level changes in various brain regions age-dependently. HMGB1 reduces in neurons, whereas it increases in astrocytes during aging. In contrast, DDSB remarkably accumulates in neurons, but it does not change significantly in astrocytes during aging. These results indicate that HMGB1 expression during aging is differentially regulated between neurons and astrocytes, and suggest that the reduction of nuclear HMGB1 might be causative for DDSB in neurons of the aged brain

  16. Successful Prednisolone Therapy in Elderly Patients with Severe Forms of Henoch–Schönlein Purpura Nephritis

    Directory of Open Access Journals (Sweden)

    Saiko Kato-Okada

    2015-01-01

    Full Text Available Introduction Recently, Henoch–Schönlein purpura (HSP has been observed in elderly people, although it was believed to be uncommon in these subjects. The increased risks of developing end-stage renal disease (ESRD in adults in comparison with children were highlighted by different studies; however, limited data are available on the treatment of HSP nephritis in adults. Methods Between 2002 and 2008, five elderly Japanese patients (>65 years old (mean age, 68 years, ranging from 65 to 72 with severe forms of HSP nephritis were entered into a prospective study to evaluate prednisolone therapy on the outcome of nephropathy in terms of clinical symptoms and histopathological changes. The patients were considered at risk of developing chronic renal failure when they presented with a nephrotic syndrome and crescentic glomeruli. Results At the last follow-up, 4–10 years after initiation of the therapy, four patients had clinically recovered and one died of lung cancer. No patients developed ESRD. The clinical outcome seemed to be correlated with glomerular activity (massive proteinuria and crescent formation. In spite of a relatively large dose of prednisolone, a few adverse effects, such as insomnia and skin lesions, were observed. Discussion Our preliminary small study suggests that renal outcome as well as survival of elderly patients with severe forms of HSP might be altered by aggressive prednisolone therapy.

  17. The own-age face recognition bias is task dependent.

    Science.gov (United States)

    Proietti, Valentina; Macchi Cassia, Viola; Mondloch, Catherine J

    2015-08-01

    The own-age bias (OAB) in face recognition (more accurate recognition of own-age than other-age faces) is robust among young adults but not older adults. We investigated the OAB under two different task conditions. In Experiment 1 young and older adults (who reported more recent experience with own than other-age faces) completed a match-to-sample task with young and older adult faces; only young adults showed an OAB. In Experiment 2 young and older adults completed an identity detection task in which we manipulated the identity strength of target and distracter identities by morphing each face with an average face in 20% steps. Accuracy increased with identity strength and facial age influenced older adults' (but not younger adults') strategy, but there was no evidence of an OAB. Collectively, these results suggest that the OAB depends on task demands and may be absent when searching for one identity. © 2014 The British Psychological Society.

  18. Cadmium induces matrix metalloproteinase-9 expression via ROS-dependent EGFR, NF-kB, and AP-1 pathways in human endothelial cells

    International Nuclear Information System (INIS)

    Lian, Sen; Xia, Yong; Khoi, Pham Ngoc; Ung, Trong Thuan; Yoon, Hyun Joong; Kim, Nam Ho; Kim, Kyung Keun; Jung, Young Do

    2015-01-01

    Highlights: • Cadmium induces MMP-9 expression through NADPH oxidase-derived ROS. • Cadmium induces MMP-9 through EGFR-mediated Akt, Erk1/2 and JNK1/2 signaling pathways. • Akt, MAPKs (Erk1/2 and JNK1/2) functioned as upstream signals of NF-kB and AP-1 respectively, in cadmium-induced MMP-9 in endothelial cells. • ROS production by NADPH oxidase is the furthest upstream signal in MMP-9 expression in ECV304 cells. - Abstract: Cadmium (Cd), a widespread cumulative pollutant, is a known human carcinogen, associated with inflammation and tumors. Matrix metalloproteinase-9 (MMP-9) plays a pivotal role in tumor metastasis; however, the mechanisms underlying the MMP-9 expression induced by Cd remain obscure in human endothelial cells. Here, Cd elevated MMP-9 expression in dose- and time-dependent manners in human endothelial cells. Cd increased ROS production and the ROS-producing NADPH oxidase. Cd translocates p47 phox , a key subunit of NADPH oxidase, to the cell membrane. Cd also activated the phosphorylation of EGFR, Akt, Erk1/2, and JNK1/2 in addition to promoting NF-kB and AP-1 binding activities. Specific inhibitor and mutagenesis studies showed that EGFR, Akt, Erk1/2, JNK1/2 and transcription factors NF-κB and AP-1 were related to Cd-induced MMP-9 expression in endothelial cells. Akt, Erk1/2, and JNK1/2 functioned as upstream signals in the activation of NF-κB and AP-1, respectively. In addition, N-acetyl-L-cystein (NAC), diphenyleneiodonium chloride (DPI) and apocynin (APO) inhibited the Cd-induced activation of EGFR, Akt, Erk1/2, JNK1/2, and p38 MAPK, indicating that ROS production by NADPH oxidase is the furthest upstream signal in MMP-9 expression. At present, it states that Cd displayed marked invasiveness in ECV304 cells, which was partially abrogated by MMP-9 neutralizing antibodies. These results demonstrated that Cd induces MMP-9 expression via ROS-dependent EGFR- > Erk1/2, JNK1/2- > AP-1 and EGFR- > Akt- > NF-κB signaling pathways and, in turn

  19. Factors promoting resident deaths at aged care facilities in Japan: a review.

    Science.gov (United States)

    Sugimoto, Kentaro; Ogata, Yasuko; Kashiwagi, Masayo

    2018-03-01

    Due to an increasingly ageing population, the Japanese government has promoted elderly deaths in aged care facilities. However, existing facilities were not designed to provide resident end-of-life care and the proportion of aged care facility deaths is currently less than 10%. Consequently, the present review evaluated the factors that promote aged care facility resident deaths in Japan from individual- and facility-level perspectives to exploring factors associated with increased resident deaths. To achieve this, MEDLINE, CINAHL, Web of Science and Ichushi databases were searched on 23 January 2016. Influential factors were reviewed for two healthcare services (insourcing and outsourcing facilities) as well as external healthcare agencies operating outside facilities. Of the original 2324 studies retrieved, 42 were included in analysis. Of these studies, five focused on insourcing, two on outsourcing, seven on external agencies and observed facility/agency-level factors. The other 28 studies identified individual-level factors related to death in aged care facilities. The present review found that at both facility and individual levels, in-facility resident deaths were associated with healthcare service provision, confirmation of resident/family end-of-life care preference and staff education. Additionally, while outsourcing facilities did not require employment of physicians/nursing staff to accommodate resident death, these facilities required visits by physicians and nursing staff from external healthcare agencies as well as residents' healthcare input. This review also found few studies examining outsourcing facilities. The number of healthcare outsourcing facilities is rapidly increasing as a result of the Japanese government's new tax incentives. Consequently, there may be an increase in elderly deaths in outsourcing healthcare facilities. Accordingly, it is necessary to identify the factors associated with residents' deaths at outsourcing facilities.

  20. Toll-like receptor 9 suppresses lupus disease in Fas-sufficient MRL Mice.

    Directory of Open Access Journals (Sweden)

    Kevin M Nickerson

    Full Text Available Genetic deficiency in TLR9 accelerates pathogenesis in the spontaneous polygenic MRL.Faslpr murine model of systemic lupus erythematosus, despite the absence of anti-nucleosome autoantibodies. However, it could be argued that this result was dependent on Fas-deficiency rather than lupus-promoting genes in the MRL genetic background. Here we report the effects of TLR9 deficiency on autoimmune disease independent of the lpr mutation in Fas by characterizing Tlr9-/- and Tlr9+/+ mice on the Fas-intact MRL/+ genetic background. By 30 weeks of age, Tlr9-deficient MRL/+ had more severe renal disease, increased T cell activation, and higher titers of anti-Sm and anti-RNA autoantibodies than Tlr9-intact animals, as had been the case in the MRL.Faslpr model. In addition, Tlr9-deficient MRL/+ mice had increased numbers of germinal center phenotype B cells and an increase in splenic neutrophils and conventional dendritic cell populations. Thus, the disease accelerating effects of Tlr9 deficiency are separable from those mediated by the Fas mutation in the lupus-prone MRL genetic background. Nonetheless, disease acceleration in Tlr9-deficient MRL/+ mice was phenotypically distinct from that in Fas-deficient counterparts, which has important implications.

  1. Messung computer- und informationsbezogener Kompetenzen von Schülerinnen und Schülern als Schlüsselkompetenz im 21. Jahrhundert

    Directory of Open Access Journals (Sweden)

    Birgit Eickelmann

    2011-12-01

    Full Text Available Mit der ICILS 2013 (International Computer and Information Literacy Study realisiert die IEA (International Association for the Evaluation of Educational Achievement erstmalig eine internationale Vergleichsstudie, die empirisch abgesichert Schülerkompetenzen im Bereich der computer- und informationsbezogenen Kompetenzen (Computer and Information Literacy, kurz: CIL erhebt. Mit dieser Studie werden informations- und computerbezogene Kompetenzen, die im 'deutschen' Sprachgebrauch auch oft unter dem affinen Begriff ICT-Literacy geführt werden, als Large-Scale-Assessments erfasst. Im folgenden Beitrag soll die Relevanz der Messung dieser Schlüsselkompetenz aufgezeigt werden. Alsdann werden das der Studie zugrundeliegende Messkonstrukt und seine definitorischen Bereiche beschrieben. Die hier vorgestellte Definition des CIL-Konstruktes bildet die Grundlage für die datengestützte Entwicklung von Kompetenzstufen, die aus der Hauptstudie von ICILS im Jahr 2013 hervorgehen werden. The IEA (International Association for the Evaluation of Educational Achievement will realize with ICILS 2013 (International Computer and Information Literacy Study for the first time an international comparative study, which will provide evidence about students' computer- and information-related competencies across countries. As a large-scaleassessment, the study examines the outcome of computer and information literacy. This article outlines the challenges and the relevance of the measurement of this core competence. Additionally the theoretical assessment constructs of CIL (computer and information literacy and their definitional scopes are explained in more detail. The presented definition of CIL is the foundation for a data-based development of proficiency levels within the study, which main survey will take place in 2013.

  2. IgA nephropathy and Henoch-Schönlein nephritis in adults : with special reference to factors affecting outcome

    OpenAIRE

    Rauta, Virpi

    2006-01-01

    IgA nephropathy (IgAN) is the most common primary glomerulonephritis. In one third of the patients the disease progresses, and they eventually need renal replacement therapy. IgAN is in most cases a slowly progressing disease, and the prediction of progression has been difficult, and the results of studies have been conflicting. Henoch-Schönlein nephritis (HSN) is rare in adults, and prediction of the outcome is even more difficult than in IgAN. This study was conducted to evaluate the c...

  3. Kinetostatic and Inertial Conditioning of the McGill Schönflies-Motion Generator

    Directory of Open Access Journals (Sweden)

    Alessandro Cammarata

    2010-01-01

    Full Text Available This paper focuses on the optimization of the McGill Schönflies Motion Generator. Recent trends on optimum design of parallel robots led us to investigate the advantages and disadvantages derived from an optimization based on performance indices. Particularly, we optimize here two different indices: the kinematic conditioning and the inertial conditioning, pertaining to the condition number of the Jacobian matrix and to that of the generalized inertia matrix of the robot, respectively. The problem of finding the characteristic length for the robot is first investigated by means of a constrained optimization problem; then plots of the kinetostatic and the inertial conditioning indices are provided for a particular trajectory to be tracked by the moving platform of the SMG. Deep connections appear between the two indices, reflecting a correlation between kinematics and dynamics.

  4. A ‘suicide’ CRISPR-Cas9 system to promote gene deletion and restoration by electroporation in Cryptococcus neoformans

    Science.gov (United States)

    Wang, Yu; Wei, Dongsheng; Zhu, Xiangyang; Pan, Jiao; Zhang, Ping; Huo, Liang; Zhu, Xudong

    2016-01-01

    Loss-of-function mutagenesis is an important tool used to characterize gene functions, and the CRISPR-Cas9 system is a powerful method for performing targeted mutagenesis in organisms that present low recombination frequencies, such as the serotype D strains of Cryptococcus neoformans. However, when the CRISPR-Cas9 system persists in the host cells, off-target effects and Cas9 cytotoxicity may occur, which might block subsequent genetic manipulation. Here, we report a method of spontaneously eliminating the CRISPR-Cas9 system without impairing its robust editing function. We successfully expressed single guide RNA under the driver of an endogenous U6 promoter and the human codon-optimized Cas9 endonuclease with an ACT1 promoter. This system can effectively generate an indel mutation and efficiently perform targeted gene disruption via homology-directed repair by electroporation in yeast. We then demonstrated the spontaneous elimination of the system via a cis arrangement of the CRISPR-Cas9 expression cassettes to the recombination construct. After a system-mediated double crossover, the CRISPR-Cas9 cassettes were cleaved and degraded, which was validated by Southern blotting. This ‘suicide’ CRISPR-Cas9 system enables the validation of gene functions by subsequent complementation and has the potential to minimize off-target effects. Thus, this technique has the potential for use in functional genomics studies of C. neoformans. PMID:27503169

  5. Aging-dependent DNA hypermethylation and gene expression of GSTM1 involved in T cell differentiation.

    Science.gov (United States)

    Yeh, Shu-Hui; Liu, Cheng-Ling; Chang, Ren-Chieh; Wu, Chih-Chiang; Lin, Chia-Hsueh; Yang, Kuender D

    2017-07-25

    This study investigated whether aging was associated with epigenetic changes of DNA hypermethylation on immune gene expression and lymphocyte differentiation. We screened CG sites of methylation in blood leukocytes from different age populations, picked up genes with age-related increase of CG methylation content more than 15%, and validated immune related genes with CG hypermethylation involved in lymphocyte differentiation in the aged population. We found that 12 genes (EXHX1、 IL-10、 TSP50、 GSTM1、SLC5A5、SPI1、F2R、LMO2、PTPN6、FGFR2、MMP9、MET) were associated with promoter or exon one DNA hypermethylation in the aged group. Two immune related genes, GSTM1 and LMO2, were chosen to validate its aging-related CG hypermethylation in different leukocytes. We are the first to validate that GSTM1_P266 and LMO2_E128 CG methylation contents in T lymphocytes but not polymorphonuclear cells (PMNs) or mononuclear cells (MNCs) were significantly increased in the aged population. The GSTM1 mRNA expression in T lymphocytes but not PMNs or MNCs was inversely associated with the GSTM1 CG hypermethylation levels in the aged population studied. Further studies showed that lower GSTM1 CG methylation content led to the higher GSTM1 mRNA expression in T cells and knockdown of GSTM1 mRNA expression decreased type 1 T helper cell (Th1) differentiation in Jurkat T cells and normal adult CD4 T cells. The GSTM1_P266 hypermethylation in the aged population associated with lower GSTM1 mRNA expression was involved in Th1 differentiation, highlighting that modulation of aging-associated GSTM1 methylation may be able to enhance T helper cell immunity in the elders.

  6. Comprehensive genetic assessment of a functional TLR9 promoter polymorphism: no replicable association with asthma or asthma-related phenotypes

    Directory of Open Access Journals (Sweden)

    Celedón Juan C

    2011-02-01

    Full Text Available Abstract Background Prior studies suggest a role for a variant (rs5743836 in the promoter of toll-like receptor 9 (TLR9 in asthma and other inflammatory diseases. We performed detailed genetic association studies of the functional variant rs5743836 with asthma susceptibility and asthma-related phenotypes in three independent cohorts. Methods rs5743836 was genotyped in two family-based cohorts of children with asthma and a case-control study of adult asthmatics. Association analyses were performed using chi square, family-based and population-based testing. A luciferase assay was performed to investigate whether rs5743836 genotype influences TLR9 promoter activity. Results Contrary to prior reports, rs5743836 was not associated with asthma in any of the three cohorts. Marginally significant associations were found with FEV1 and FVC (p = 0.003 and p = 0.008, respectively in one of the family-based cohorts, but these associations were not significant after correcting for multiple comparisons. Higher promoter activity of the CC genotype was demonstrated by luciferase assay, confirming the functional importance of this variant. Conclusion Although rs5743836 confers regulatory effects on TLR9 transcription, this variant does not appear to be an important asthma-susceptibility locus.

  7. Postpartum follow-up in women diagnosed with subclinical hypothyroidism during pregnancy

    Directory of Open Access Journals (Sweden)

    K Neelaveni

    2017-01-01

    Full Text Available Background: Management guidelines about the thyroid disease in pregnancy are silent about the postpartum course of new onset subclinical hypothyroidism (SCH. Hence, we analyzed the 2 years outcome of SCH diagnosed during pregnancy. Materials and Methods: We conducted this retrospective study using the medical records of patients with new onset SCH during pregnancy between 2010 and 2013 (n = 718. Patients who stopped their levothyroxine after delivery with a 2-year follow-up record were included. We excluded patients with known thyroid disorders and continuous use of drugs that affect the thyroid results. The patients were divided into two groups (Group 1 – euthyroid and Group 2 – hypothyroid based on the final outcome after 2 years. The data were analyzed using appropriate statistical methods and a P < 0.05 was considered statically significant. Results: A total of 559 (77.8% women stopped levothyroxine after delivery, and the final follow-up data were available for 467 patients only. At the end of 2 years, 384 (82.2% remained euthyroid, and the remaining 83 (17.8% developed hypothyroidism. SCH and overt hypothyroidism were seen in 22 and 61 patients, respectively. Group 2 patients had higher mean age (25.5 vs. 23.6 years, goiter (51 vs. 2%, initial thyroid stimulating hormone (7.9 vs. 5.1 μIU/mL, and thyroid antibody positivity (76 vs. 13% (P < 0.001. Conclusion: The majority of patients with SCH during pregnancy remain euthyroid after delivery. Advanced age, goiter, positive family history, and thyroid autoimmunity increase the future risk of hypothyroidism in patients with SCH diagnosed during pregnancy.

  8. Age-Dependent Cellular and Behavioral Deficits Induced by Molecularly Targeted Drugs Are Reversible.

    Science.gov (United States)

    Scafidi, Joseph; Ritter, Jonathan; Talbot, Brooke M; Edwards, Jorge; Chew, Li-Jin; Gallo, Vittorio

    2018-04-15

    Newly developed targeted anticancer drugs inhibit signaling pathways commonly altered in adult and pediatric cancers. However, as these pathways are also essential for normal brain development, concerns have emerged of neurologic sequelae resulting specifically from their application in pediatric cancers. The neural substrates and age dependency of these drug-induced effects in vivo are unknown, and their long-term behavioral consequences have not been characterized. This study defines the age-dependent cellular and behavioral effects of these drugs on normally developing brains and determines their reversibility with post-drug intervention. Mice at different postnatal ages received short courses of molecularly targeted drugs in regimens analagous to clinical treatment. Analysis of rapidly developing brain structures important for sensorimotor and cognitive function showed that, while adult administration was without effect, earlier neonatal administration of targeted therapies attenuated white matter oligodendroglia and hippocampal neuronal development more profoundly than later administration, leading to long-lasting behavioral deficits. This functional impairment was reversed by rehabilitation with physical and cognitive enrichment. Our findings demonstrate age-dependent, reversible effects of these drugs on brain development, which are important considerations as treatment options expand for pediatric cancers. Significance: Targeted therapeutics elicit age-dependent long-term consequences on the developing brain that can be ameliorated with environmental enrichment. Cancer Res; 78(8); 2081-95. ©2018 AACR . ©2018 American Association for Cancer Research.

  9. Single-step generation of gene knockout-rescue system in pluripotent stem cells by promoter insertion with CRISPR/Cas9.

    Science.gov (United States)

    Matsunaga, Taichi; Yamashita, Jun K

    2014-02-07

    Specific gene knockout and rescue experiments are powerful tools in developmental and stem cell biology. Nevertheless, the experiments require multiple steps of molecular manipulation for gene knockout and subsequent rescue procedures. Here we report an efficient and single step strategy to generate gene knockout-rescue system in pluripotent stem cells by promoter insertion with CRISPR/Cas9 genome editing technology. We inserted a tetracycline-regulated inducible gene promoter (tet-OFF/TRE-CMV) upstream of the endogenous promoter region of vascular endothelial growth factor receptor 2 (VEGFR2/Flk1) gene, an essential gene for endothelial cell (EC) differentiation, in mouse embryonic stem cells (ESCs) with homologous recombination. Both homo- and hetero-inserted clones were efficiently obtained through a simple selection with a drug-resistant gene. The insertion of TRE-CMV promoter disrupted endogenous Flk1 expression, resulting in null mutation in homo-inserted clones. When the inserted TRE-CMV promoter was activated with doxycycline (Dox) depletion, Flk1 expression was sufficiently recovered from the downstream genomic Flk1 gene. Whereas EC differentiation was almost completely perturbed in homo-inserted clones, Flk1 rescue with TRE-CMV promoter activation restored EC appearance, indicating that phenotypic changes in EC differentiation can be successfully reproduced with this knockout-rescue system. Thus, this promoter insertion strategy with CRISPR/Cas9 would be a novel attractive method for knockout-rescue experiments. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. E1A FUNCTIONS AS A COACTIVATOR OF RETINOIC ACID-DEPENDENT RETINOIC ACID RECEPTOR-BETA-2 PROMOTER ACTIVATION

    NARCIS (Netherlands)

    KRUYT, FAE; FOLKERS, GE; WALHOUT, AJM; VANDERLEEDE, BM; VANDERSAAG, PT; Kruyt, Frank

    The retinoic acid (RA) receptor (RAR) beta2 promoter is strongly activated by RA in embryonal carcinoma (EC) cells. We examined this activation in the P19 EC-derived END-2 cell line and in E1A-expressing counterparts and found strong RA-dependent RARbeta2 promoter activation in the E1A-expressing

  11. Stability analysis of a general age-dependent vaccination model of a vertically transmitted disease

    International Nuclear Information System (INIS)

    El Doma, M.

    1995-07-01

    An SIR epidemic model of a general age-dependent vaccination of a vertically as well as horizontally transmitted disease is investigated when the population is in steady state and the fertility, mortality and removal rates depends on age. We determine the steady states and examine their stabilities. (author). 24 refs

  12. Murine Th9 cells promote the survival of myeloid dendritic cells in cancer immunotherapy.

    Science.gov (United States)

    Park, Jungsun; Li, Haiyan; Zhang, Mingjun; Lu, Yong; Hong, Bangxing; Zheng, Yuhuan; He, Jin; Yang, Jing; Qian, Jianfei; Yi, Qing

    2014-08-01

    Dendritic cells (DCs) are professional antigen-presenting cells to initiate immune responses, and DC survival time is important for affecting the strength of T-cell responses. Interleukin (IL)-9-producing T-helper (Th)-9 cells play an important role in anti-tumor immunity. However, it is unclear how Th9 cells communicate with DCs. In this study, we investigated whether murine Th9 cells affected the survival of myeloid DCs. DCs derived from bone marrow of C57BL/6 mice were cocultured with Th9 cells from OT-II mice using transwell, and the survival of DCs was examined. DCs cocultured with Th9 cells had longer survival and fewer apoptotic cells than DCs cultured alone in vitro. In melanoma B16-OVA tumor-bearing mice, DCs conditioned by Th9 cells lived longer and induced stronger anti-tumor response than control DCs did in vivo. Mechanistic studies revealed that IL-3 but not IL-9 secreted by Th9 cells was responsible for the prolonged survival of DCs. IL-3 upregulated the expression of anti-apoptotic protein Bcl-xL and activated p38, ERK and STAT5 signaling pathways in DCs. Taken together, our data provide the first evidence that Th9 cells can promote the survival of DCs through IL-3, and will be helpful for designing Th9 cell immunotherapy and more effective DC vaccine for human cancers.

  13. Synthesis of Au38(SCH2CH2Ph)24, Au36(SPh-tBu)24, and Au30(S-tBu)18 Nanomolecules from a Common Precursor Mixture.

    Science.gov (United States)

    Rambukwella, Milan; Dass, Amala

    2017-10-17

    Phenylethanethiol protected nanomolecules such as Au 25 , Au 38 , and Au 144 are widely studied by a broad range of scientists in the community, owing primarily to the availability of simple synthetic protocols. However, synthetic methods are not available for other ligands, such as aromatic thiol and bulky ligands, impeding progress. Here we report the facile synthesis of three distinct nanomolecules, Au 38 (SCH 2 CH 2 Ph) 24 , Au 36 (SPh-tBu) 24 , and Au 30 (S-tBu) 18 , exclusively, starting from a common Au n (glutathione) m (where n and m are number of gold atoms and glutathiolate ligands) starting material upon reaction with HSCH 2 CH 2 Ph, HSPh-tBu, and HStBu, respectively. The systematic synthetic approach involves two steps: (i) synthesis of kinetically controlled Au n (glutathione) m crude nanocluster mixture with 1:4 gold to thiol molar ratio and (ii) thermochemical treatment of the purified nanocluster mixture with excess thiols to obtain thermodynamically stable nanomolecules. Thermochemical reactions with physicochemically different ligands formed highly monodispersed, exclusively three different core-size nanomolecules, suggesting a ligand induced core-size conversion and structural transformation. The purpose of this work is to make available a facile and simple synthetic method for the preparation of Au 38 (SCH 2 CH 2 Ph) 24 , Au 36 (SPh-tBu) 24 , and Au 30 (S-tBu) 18 , to nonspecialists and the broader scientific community. The central idea of simple synthetic method was demonstrated with other ligand systems such as cyclopentanethiol (HSC 5 H 9 ), cyclohexanethiol(HSC 6 H 11 ), para-methylbenzenethiol(pMBT), 1-pentanethiol(HSC 5 H 11 ), 1-hexanethiol(HSC 6 H 13 ), where Au 36 (SC 5 H 9 ) 24 , Au 36 (SC 6 H 11 ) 24 , Au 36 (pMBT) 24 , Au 38 (SC 5 H 11 ) 24 , and Au 38 (SC 6 H 13 ) 24 were obtained, respectively.

  14. Corticosteroid therapy in Henoch-Schönlein gastritis

    Directory of Open Access Journals (Sweden)

    Pavlović Momčilo

    2007-01-01

    Full Text Available Introduction. Henoch-Schönlein purpura (HSP is the most common vascular disease of childhood. It is a multisystem disease most commonly affecting the skin, joints, gastrointestinal tract, and kidneys, but other organs may be affected, too. Gastrointestinal involvement occurs in approximately 65-90% of patients, ranging from mild symptoms such as abdominal pain, nausea, and vomiting, to more severe manifestations such as gastrointestinal bleeding and intussusception. In most cases, HSP spontaneously resolves without treatment. The use of corticosteroids is controversial and usually reserved for severe systemic manifestations. Some authors suggest that the abdominal pain and gastrointestinal hemorrhage of HSP may respond to steroids, with some suggesting that there is a benefit in their use and describing a regimen. Case outline. This is a case report of HSP in a fourteen year-old boy with abdominal pain and hematemesis. Upper endoscopy showed an edematous and erythematous change in the body of the stomach and purpuric lesions in the duodenum, while multiple erosions were found in the antral area. Parenteral corticosteroid therapy with gastric acid secretion inhibitor administration led to regression of gastrointestinal symptoms on the seventh day, with relapses on the fourth and sixth day. Peroral administration of corticosteroids and gradual decrease of daily doses started on the eighth day of abdominal symptoms. New purpuric skin rashes appeared during six weeks. Conclusion. Corticosteroid therapy with gastric acid secretion inhibitors showed a positive effect in our patient with a severe form of HSP accompanied by abdominal pain and gastrointestinal hemorrhage. .

  15. The constitutive activation of the CEF-4/9E3 chemokine gene depends on C/EBPbeta in v-src transformed chicken embryo fibroblasts

    DEFF Research Database (Denmark)

    Gagliardi, M; Maynard, S; Bojovic, B

    2001-01-01

    The CEF-4/9E3 chemokine gene is expressed constitutively in chicken embryo fibroblasts (CEF) transformed by the Rous sarcoma virus (RSV). This aberrant induction is controlled at the transcriptional and post-transcriptional levels. Transcriptional activation depends on multiple elements of the CEF....../EBPbeta binds to a second element located in proximity of the TRE. A mutation of this distal CAAT box impaired the activation of the CEF-4 promoter by pp60(v-src) indicating that this element is also part of the SRU. Using the RCASBP retroviral vector, we expressed a dominant negative mutant of C....../EBPbeta (designated Delta184-C/EBPbeta) in RSV-transformed CEF. Delta184-C/EBPbeta decreased the accumulation of the CEF-4 mRNA and activation of the CEF-4 promoter by pp60(v-src). The induction of the Cox-2 gene (CEF-147) was also reduced by Delta184-C/EBPbeta. The effect of the dominant negative mutant was observed...

  16. Sediment budgets of unglaciated alpine catchments - the example of the Johnsbach and Schöttlbach valleys in Styria

    Science.gov (United States)

    Sass, Oliver; Rascher, Eric; Stangl, Johannes; Lutzmann, Silke

    2017-04-01

    Extensive research has been performed in glacier forefields and in glaciated catchments in order to predict their future behaviour in a warming climate. However, the majority of medium-scale torrential catchments in the European Alps are non-glaciated and their response to disturbance events (e.g. changing climate) is more subtle and hard to predict. We report from two torrential catchments in the Eastern Alps, the Johnsbach and the Schöttlbach valleys, that have been monitored for several years. The catchments are located in Styria (Austria) and are remarkably similar in terms of size (60-70 km3) and elevation (600/800 - 2400 m). The main difference is the geological setting of the sediment delivering areas which is limestone and brittle dolomite at Johnsbach, and a prominent late-pleistocene valley fill at Schöttlbach, respectively. Slope processes in both areas were monitored by means of repeated TLS surveys of active slope and channel areas and by ALS and/or UAV surveys. Fluvial transport in the main channels was measured using Helly-Smith samplers and recorded continuously by means of new developed, low-budget sediment impact sensors (SIS). In both areas, the catchment output was quantified: by regular surveys of a retention basin at Schöttlbach and by a bedload measurement station (geophone sill) at Johnsbach. The results show that at Johnsbach, the sediment source areas are active tributary trenches in the lower third of the catchment. The sediments derive from brittle dolomite rockwalls and are transported to the main river episodically during rainstorm events. In a 2-yr period, 7400 m3 yr-1 were eroded in the surveyed areas and 9900 m3 yr-1 m3 yr-1 were deposited; of this amount, only a minor portion of 650 m3 yr-1 reached the Johnsbach River. The degree of coupling between tributaries and creek is strongly influenced by anthropogenic measures, e.g. former disturbance by gravel mining and undersized bridge openings. Besides limited bank erosion

  17. Age- and gender-dependent values of skeletal muscle mass in healthy children and adolescents.

    Science.gov (United States)

    Webber, Colin E; Barr, Ronald D

    2012-03-01

    Skeletal muscle mass (SMM) can be extracted from whole-body scans obtained by X-ray-based dual-photon absorptiometry (DXA). There is a need to establish expected age-dependent values for children and adolescents. Appendicular lean tissue mass (ALM) was extracted from whole-body DXA scans in 140 healthy children and adolescents (68 females and 72 males). Whole-body SMM was calculated from ALM using equations developed by Kim et al. (Am J Clin Nutr 84:1014-1020, 2006). Age-dependent patterns of increase in SMM were derived by fitting SMM values to equations that consisted of the sum of two logistic expressions, one accounting for SMM changes during growth and the other for SMM changes during puberty. Normal ranges were defined so that 95% of the SMM values were included. The reproducibility of SMM measurements was obtained from whole-body DXA scans repeated on three occasions in each of a separate group of 32 normal children with repositioning between scans. Normal ranges are presented as equations describing the age-dependent pattern of increase in SMM as well as population standard deviations that increased steadily with age. For 15 children below age 10, SMM reproducibility (95% CI) was 149 g (119-199 g) while for 17 children and adolescents over age 10, reproducibility was 170 g (138-223 g). DXA-based measurements of SMM in children and adolescents are reproducible and can be expressed in terms of age-dependent Z scores.

  18. Interleukin-10 overexpression promotes Fas-ligand-dependent chronic macrophage-mediated demyelinating polyneuropathy.

    Directory of Open Access Journals (Sweden)

    Dru S Dace

    Full Text Available BACKGROUND: Demyelinating polyneuropathy is a debilitating, poorly understood disease that can exist in acute (Guillain-Barré syndrome or chronic forms. Interleukin-10 (IL-10, although traditionally considered an anti-inflammatory cytokine, has also been implicated in promoting abnormal angiogenesis in the eye and in the pathobiology of autoimmune diseases such as lupus and encephalomyelitis. PRINCIPAL FINDINGS: Overexpression of IL-10 in a transgenic mouse model leads to macrophage-mediated demyelinating polyneuropathy. IL-10 upregulates ICAM-1 within neural tissues, promoting massive macrophage influx, inflammation-induced demyelination, and subsequent loss of neural tissue resulting in muscle weakness and paralysis. The primary insult is to perineural myelin followed by secondary axonal loss. Infiltrating macrophages within the peripheral nerves demonstrate a highly pro-inflammatory signature. Macrophages are central players in the pathophysiology, as in vivo depletion of macrophages using clodronate liposomes reverses the phenotype, including progressive nerve loss and paralysis. Macrophage-mediate demyelination is dependent on Fas-ligand (FasL-mediated Schwann cell death. SIGNIFICANCE: These findings mimic the human disease chronic idiopathic demyelinating polyneuropathy (CIDP and may also promote further understanding of the pathobiology of related conditions such as acute idiopathic demyelinating polyneuropathy (AIDP or Guillain-Barré syndrome.

  19. Thiolato-technetium complexes. 5. Synthesis, characterization, and electrochemical properties of bis(o-phenylenebis(dimethylarsine))technetium(II) and -technetium(III) complexes with thiolato ligands. Single-crystal structural analyses of trans-[Tc(SCH3)2(DIARS)2]PF6 and trans-[Tc(SC6H5)2(DIARS)2]0

    International Nuclear Information System (INIS)

    Konno, Takumi; Heineman, W.R.; Deutsch, E.; Kirchhoff, J.R.; Heeg, M.J.; Stuckey, J.A.

    1992-01-01

    Three different thiols have been brought into reaction with trans-[Tc(OH)(O)(DIARS) 2 ] 2+ to produce initially the Tc(II) complex, [Tc(SR) 2 (DIARS) 2 ] 0 , which can be oxidized to the Tc(III) complex, [Tc(SR) 2 (DIARS) 2 ] + (DIARS = o-phenylenebis(dimethylarsine)). In the case of SR = SCH 3 and SCH 2 C 6 H 5 , the Tc(II) and Tc(III) products were found to be in the trans geometry, while for SR = SC 6 H 5 , both cis and trans isomers were generated. Two of the complexes were structurally characterized by X-ray diffraction. trans-[Tc(SCH 3 ) 2 (DIARS) 2 ]PF 6 , chemical formula TcAs 4 S 2 PF 6 C 22 H 38 , crystallizes in the monoclinic space group. The Tc atom occupies an inversion center. Representative elemental analyses, FAB mass spectra, and visible-UV spectra are reported. Electrochemical and spectroelectrochemical measurements were taken on trans-[Tc(SCH 3 ) 2 (DIARS) 2 ] + , trans-[Tc(SCH 2 C 6 H 5 ) 2 (DIARS) 2 ] + , and cis-[Tc(SC 6 H 5 ) 2 (DIARS) 2 ] + , which exhibit a reversible Tc(III/II) redox couple in the range -0.32 to -0.47 V vs. Ag/AgCl. Another redox couple is present in the range -1.22 to -1.70 V; this is ascribed to Tc(II/I) and is reversible only for SR = SCH 2 C 6 H 5 at 20C. At room temperature, chemically irreversible couples are exhibited at ca. +1.0 V for Tc(IV/III)

  20. Disposal of residues according paragraph 97 StrlSchV - Efficient self control and handling of applications for release from regulatory control; Entsorgung von Rueckstaenden nach paragraph 97 StrlSchV - effektive Selbstueberwachung und Bearbeitung von Entlassungsverfahren

    Energy Technology Data Exchange (ETDEWEB)

    Gellermann, R. [HGN Hydrogeologie GmbH, Braunschweig (Germany)

    2005-07-01

    To control residues according to paragraph 97 of the German Radiation Protection Ordinance (StrlSchV), the ordinance earmarks a self - control of involved companies in the case of very low specific activities, an authorisation of release from regulatory control to disposal in the case of higher specific activities and a balancing of disposed activities in the case of large amounts. The realisation of this regulation requires the exchange of information between owners of residues, disposing companies and authorities. In order to make this information available and controllable in an efficient way, a well structured system of documents was developed analogue to an existing system in waste management. Practical experiences with this system are discussed. (orig.)

  1. Estudo da validade e confiabilidade intra e interobservador da versão modificada do teste de Schöber modificado em indivíduos com lombalgia Study of validity and intra and inter-observer reliability of modified-modified Schöber test in subjects with low-back pain

    Directory of Open Access Journals (Sweden)

    Christiane de Souza Guerino Macedo

    2009-09-01

    Full Text Available Em pacientes com lombalgia, mensura-se a amplitude de movimento (ADM da coluna lombar por meio da versão modificada do teste de Schöber modificado (MTSM, mas suas propriedades psicométricas não são comprovadas para uso clínico. Este estudo verificou a validade e confiabilidade intra e interobservador do MTSM em indivíduos com lombalgia, comparando as medidas da ADM com as obtidas por meio de radiografia, método considerado padrão-ouro. Participaram 20 voluntários com lombalgia, de ambos os sexos, funcionários de um Hospital Universitário. O MTSM foi aplicado duas vezes por dois avaliadores. As medidas obtidas pelo teste e por radiografia foram comparadas usando o coeficiente de correlação de Pearson, obtendo-se r=0,14, ou seja, correlação fraca. O coeficiente de correlação intraclasse (CCI dos MTSM intra-observador foi 0,96 (IC 95% 0,91;0,98 e interobservador 0,93 (IC 95% 0,84;0,97, indicando alta confiabilidade; o teste de Bland & Altman mostrou alta concordância intra e interobservador, com valores de -0,21 e -0,28, respectivamente. Embora tenha sido encontrada alta confiabilidade intra e interobservador na aplicação da versão modificada do teste de Schöber modificado, este apresentou baixa validade para medir a ADM da coluna lombar, quando comparado ao padrão-ouro.In patients with low-back pain the lumbar spine range of motion (ROM is often measured by the modified version of the modified Schöber test (MMST, but its psychometric properties have not been ascertained for clinical use. The purpose here was to verify intra and inter-observer validity and reliability of the MMST in subjects with low-back pain, and to compare obtained ROM measures to those obtained by radiography, taken as gold standard. The study involved 20 subjects with chronic low-back pain, of both sexes, employees at a university hospital. The MMST was applied twice by two examiners each. The Pearson correlation coefficient found when comparing

  2. Fluvastatin inhibits AGE-induced cell proliferation and migration via an ERK5-dependent Nrf2 pathway in vascular smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Ae-Rang Hwang

    Full Text Available Advanced glycation endproduct (AGE-induced vascular smooth muscle cell (VSMC proliferation and reactive oxygen species (ROS production are emerging as important mechanisms of diabetic vasculopathy, but little is known about the molecular mechanism responsible for the antioxidative effects of statins on AGEs. It has been reported that statins exert pleiotropic effects on the cardiovascular system due to decreases in AGE-induced cell proliferation, migration, and vascular inflammation. Thus, in the present study, the authors investigated the molecular mechanism by which statins decrease AGE-induced cell proliferation and VSMC migration. In cultured VSMCs, statins upregulated Nrf2-related antioxidant gene, NQO1 and HO-1, via an ERK5-dependent Nrf2 pathway. Inhibition of ERK5 by siRNA or BIX02189 (a specific ERK5 inhibitor reduced the statin-induced upregulations of Nrf2, NQO1, and HO-1. Furthermore, fluvastatin was found to significantly increase ARE promoter activity through ERK5 signaling, and to inhibit AGE-induced VSMC proliferation and migration as determined by MTT assay, cell counting, FACS analysis, a wound scratch assay, and a migration chamber assay. In addition, AGE-induced proliferation was diminished in the presence of Ad-CA-MEK5α encoding a constitutively active mutant form of MEK5α (an upstream kinase of ERK5, whereas depletion of Nrf2 restored statin-mediated reduction of AGE-induced cell proliferation. Moreover, fluvastatin suppressed the protein expressions of cyclin D1 and Cdk4, but induced p27, and blocked VSMC proliferation by regulating cell cycle. These results suggest statin-induced activation of an ERK5-dependent Nrf2 pathway reduces VSMC proliferation and migration induced by AGEs, and that the ERK5-Nrf2 signal module be viewed as a potential therapeutic target of vasculopathy in patients with diabetes and complications of the disease.

  3. Sex differences in the effects of juvenile and adult diet on age-dependent reproductive effort.

    Science.gov (United States)

    Houslay, T M; Hunt, J; Tinsley, M C; Bussière, L F

    2015-05-01

    Sexual selection should cause sex differences in patterns of resource allocation. When current and future reproductive effort trade off, variation in resource acquisition might further cause sex differences in age-dependent investment, or in sensitivity to changes in resource availability over time. However, the nature and prevalence of sex differences in age-dependent investment remain unclear. We manipulated resource acquisition at juvenile and adult stages in decorated crickets, Gryllodes sigillatus, and assessed effects on sex-specific allocation to age-dependent reproductive effort (calling in males, fecundity in females) and longevity. We predicted that the resource and time demands of egg production would result in relatively consistent female strategies across treatments, whereas male investment should depend sharply on diet. Contrary to expectations, female age-dependent reproductive effort diverged substantially across treatments, with resource-limited females showing much lower and later investment in reproduction; the highest fecundity was associated with intermediate lifespans. In contrast, long-lived males always signalled more than short-lived males, and male age-dependent reproductive effort did not depend on diet. We found consistently positive covariance between male reproductive effort and lifespan, whereas diet altered this covariance in females, revealing sex differences in the benefits of allocation to longevity. Our results support sex-specific selection on allocation patterns, but also suggest a simpler alternative: males may use social feedback to make allocation decisions and preferentially store resources as energetic reserves in its absence. Increased calling effort with age therefore could be caused by gradual resource accumulation, heightened mortality risk over time, and a lack of feedback from available mates. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary

  4. Maternal care, mother-offspring aggregation and age-dependent coadaptation in the European earwig.

    Science.gov (United States)

    Gómez, Y; Kölliker, M

    2013-09-01

    Benefits and costs of parental care are expected to change with offspring development and lead to age-dependent coadaptation expressed as phenotypic (behavioural) matches between offspring age and parental reproductive stage. Parents and offspring interact repeatedly over time for the provision of parental care. Their behaviours should be accordingly adjusted to each other dynamically and adaptively, and the phenotypic match between offspring age and parental stage should stabilize the repeated behavioural interactions. In the European earwig (Forficula auricularia), maternal care is beneficial for offspring survival, but not vital, allowing us to investigate the extent to which the stability of mother-offspring aggregation is shaped by age-dependent coadaptation. In this study, we experimentally cross-fostered nymphs of different age classes (younger or older) between females in early or late reproductive stage to disrupt age-dependent coadaptation, thereby generating female-nymph dyads that were phenotypically matched or mismatched. The results revealed a higher stability in aggregation during the first larval instar when care is most intense, a steeper decline in aggregation tendency over developmental time and a reduced developmental rate in matched compared with mismatched families. Furthermore, nymph survival was positively correlated with female-nymph aggregation stability during the early stages when maternal care is most prevalent. These results support the hypothesis that age-related phenotypically plastic coadaptation affects family dynamics and offspring developmental rate. © 2013 The Authors. Journal of Evolutionary Biology © 2013 European Society For Evolutionary Biology.

  5. Δ9-Tetrahydrocannabinol (Δ9-THC) Promotes Neuroimmune-Modulatory MicroRNA Profile in Striatum of Simian Immunodeficiency Virus (SIV)-Infected Macaques.

    Science.gov (United States)

    Simon, Liz; Song, Keijing; Vande Stouwe, Curtis; Hollenbach, Andrew; Amedee, Angela; Mohan, Mahesh; Winsauer, Peter; Molina, Patricia

    2016-03-01

    Cannabinoid administration before and after simian immunodeficiency virus (SIV)-inoculation ameliorated disease progression and decreased inflammation in male rhesus macaques. Δ9-tetrahydrocannabinol (Δ9-THC) did not increase viral load in brain tissue or produce additive neuropsychological impairment in SIV-infected macaques. To determine if the neuroimmunomodulation of Δ9-THC involved differential microRNA (miR) expression, miR expression in the striatum of uninfected macaques receiving vehicle (VEH) or Δ9-THC (THC) and SIV-infected macaques administered either vehicle (VEH/SIV) or Δ9-THC (THC/SIV) was profiled using next generation deep sequencing. Among the 24 miRs that were differentially expressed among the four groups, 16 miRs were modulated by THC in the presence of SIV. These 16 miRs were classified into four categories and the biological processes enriched by the target genes determined. Our results indicate that Δ9-THC modulates miRs that regulate mRNAs of proteins involved in 1) neurotrophin signaling, 2) MAPK signaling, and 3) cell cycle and immune response thus promoting an overall neuroprotective environment in the striatum of SIV-infected macaques. This is also reflected by increased Brain Derived Neurotrophic Factor (BDNF) and decreased proinflammatory cytokine expression compared to the VEH/SIV group. Whether Δ9-THC-mediated modulation of epigenetic mechanisms provides neuroprotection in other regions of the brain and during chronic SIV-infection remains to be determined.

  6. Activation of α7nAChR Promotes Diabetic Wound Healing by Suppressing AGE-Induced TNF-α Production.

    Science.gov (United States)

    Dong, Miao-Wu; Li, Ming; Chen, Jie; Fu, Tong-Tong; Lin, Ke-Zhi; Ye, Guang-Hua; Han, Jun-Ge; Feng, Xiang-Ping; Li, Xing-Biao; Yu, Lin-Sheng; Fan, Yan-Yan

    2016-04-01

    Diabetes frequently presents accumulation of advanced glycation end products (AGEs), which might induce excessive TNF-α production from macrophages to cause impaired wound healing. Recent studies have shown that activation of α7 nicotinic acetylcholine receptor (α7nAChR) on macrophages efficiently suppressed TNF-α synthesis. The aim of this study was to investigate the accumulation of AGEs in the wounds and determine whether PNU282987, an α7nAChR agonist, can improve wound repair by inhibiting AGE-mediated TNF-α production in a streptozotocin (STZ)-induced diabetic mouse model. Animals were assigned into four groups: wounded control group, wounded diabetic group, wounded diabetic group treated intraperitoneally with PNU282987, or wounded diabetic group treated intraperitoneally with vehicle. Compared with the non-diabetic control mice, the diabetic mice exhibited delayed wound healing that was characterized by elevated accumulation of AGEs, increased TNF-α level and macrophage infiltration, and decreased fibroblast number and collagen deposition at the late stage of repair. Besides, macrophages of diabetic wounds showed expression of α7nAChR. During late repair, PNU282987 treatment of diabetic mice significantly reduced the level of TNF-α, accelerated wound healing, and elevated fibroblast number and collagen deposition. To investigate the cellular mechanism of these observations, RAW 264.7 cells, a macrophage cell line, were incubated with AGEs in the presence or absence of PNU282987. TNF-α production from AGE-stimulated macrophages was significantly decreased by PNU282987 in a dose-dependent manner. Furthermore, PNU282987 significantly inhibited AGE-induced nuclear factor-κB (NF-κB) activation and receptor for AGE (RAGE) expression. These results strongly suggest that activating α7nAChR can promote diabetic wound healing by suppressing AGE-induced TNF-α production, which may be closely associated with the blockage of NF-κB activation in macrophages.

  7. Games of age-dependent prevention of chronic infections by social distancing.

    Science.gov (United States)

    Reluga, Timothy C; Li, Jing

    2013-06-01

    Epidemiological games combine epidemic modelling with game theory to assess strategic choices in response to risks from infectious diseases. In most epidemiological games studied thus-far, the strategies of an individual are represented with a single choice parameter. There are many natural situations where strategies can not be represented by a single dimension, including situations where individuals can change their behavior as they age. To better understand how age-dependent variations in behavior can help individuals deal with infection risks, we study an epidemiological game in an SI model with two life-history stages where social distancing behaviors that reduce exposure rates are age-dependent. When considering a special case of the general model, we show that there is a unique Nash equilibrium when the infection pressure is a monotone function of aggregate exposure rates, but non-monotone effects can appear even in our special case. The non-monotone effects sometimes result in three Nash equilibria, two of which have local invasion potential simultaneously. Returning to a general case, we also describe a game with continuous age-structure using partial-differential equations, numerically identify some Nash equilibria, and conjecture about uniqueness.

  8. Oxidative stress by monosodium urate crystals promotes renal cell apoptosis through mitochondrial caspase-dependent pathway in human embryonic kidney 293 cells: mechanism for urate-induced nephropathy.

    Science.gov (United States)

    Choe, Jung-Yoon; Park, Ki-Yeun; Kim, Seong-Kyu

    2015-01-01

    The aim of this study is to clarify the effect of oxidative stress on monosodium urate (MSU)-mediated apoptosis of renal cells. Quantitative real-time polymerase chain reaction and immunoblotting for Bcl-2, caspase-9, caspase-3, iNOS, cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), IL-18, TNF receptor-associated factor-6 (TRAF-6), and mitogen-activated protein kinases were performed on human embryonic kidney 293 (HEK293) cells, which were stimulated by MSU crystals. Fluorescence-activated cell sorting was performed using annexin V for assessment of apoptosis. Reactive oxygen species (ROS) were measured. IL-1β siRNA was used for blocking IL-1β expression. MSU crystals promoted ROS, iNOS, and COX-2 expression and also increased TRAF-6 and IL-1β expression in HEK293 cells, which was inhibited by an antioxidant ascorbic acid. Caspase-dependent renal cell apoptosis was induced through attenuation of Bcl-2 and enhanced caspase-3 and caspase-9 expression by MSU crystals, which was significantly reversed by ascorbic acid and transfection of IL-1β siRNA to HEK293 cells. Ascorbic acid inhibited phosphorylation of extracellular signal-regulated kinase and Jun N-terminal protein kinase stimulated by MSU crystals. ROS accumulation and iNOS and COX-2 mRNA expression by MSU crystals was also suppressed by transfection with IL-1β siRNA. Oxidative stress generated by MSU crystals promotes renal apoptosis through the mitochondrial caspase-dependent apoptosis pathway.

  9. S100A9 is a novel ligand of EMMPRIN that promotes melanoma metastasis.

    Science.gov (United States)

    Hibino, Toshihiko; Sakaguchi, Masakiyo; Miyamoto, Shoko; Yamamoto, Mami; Motoyama, Akira; Hosoi, Junichi; Shimokata, Tadashi; Ito, Tomonobu; Tsuboi, Ryoji; Huh, Nam-Ho

    2013-01-01

    The calcium-binding proteins S100A8 and S100A9 can dimerize to form calprotectin, the release of which during tissue damage has been implicated in inflammation and metastasis. However, receptor(s) mediating the physiologic and pathophysiologic effects of this damage-associated "danger signal" are uncertain. In this study, searching for candidate calprotectin receptors by affinity isolation-mass spectrometry, we identified the cell surface glycoprotein EMMPRIN/BASIGIN (CD147/BSG). EMMPRIN specifically bound to S100A9 but not S100A8. Induction of cytokines and matrix metalloproteases (MMP) by S100A9 was markedly downregulated in melanoma cells by attenuation of EMMPRIN. We found that EMMPRIN signaling used the TNF receptor-associated factor TRAF2 distinct from the known S100-binding signaling pathway mediated by RAGE (AGER). S100A9 strongly promoted migration when EMMPRIN was highly expressed, independent of RAGE, whereas EMMPRIN blockade suppressed migration by S100A9. Immunohistologic analysis of melanomas revealed that EMMPRIN was expressed at both the invasive edge of lesions and the adjacent epidermis, where S100A9 was also strongly expressed. In epidermal-specific transgenic mice, tail vein-injected melanoma accumulated in skin expressing S100A9 but not S100A8. Together, our results establish EMMPRIN as a receptor for S100A9 and suggest the therapeutic use in targeting S100A9-EMMPRIN interactions.

  10. Shorter preschool, leukocyte telomere length is associated with obesity at age 9 in Latino children.

    Science.gov (United States)

    Kjaer, T W; Faurholt-Jepsen, D; Mehta, K M; Christensen, V B; Epel, E; Lin, J; Blackburn, E; Wojcicki, J M

    2018-04-01

    The aim of this study was to determine the potential role of leukocyte telomere length as a biomarker for development of childhood obesity in a low-income Latino population. A birth cohort of Latino children (N = 201) in San Francisco (recruited May 2006-May 2007) was followed until age 9 and assessed annually for obesity and dietary intake. Leukocyte telomere length was measured at 4 and 5 years (n = 102) and assessed as a predictor for obesity at age 9, adjusting for known risk factors. Furthermore, leukocyte telomere length at age 4 and 5 was evaluated as a possible mediator of the relationship between excessive sugar-sweetened beverage consumption and obesity at age 9. Shorter leukocyte telomere length in preschoolers was associated with obesity at age 9 (adjusted odds ratio 0.35, 95% confidence interval 0.13-0.94) after adjustment for known risk factors. Telomere length mediated 11% of the relationship between excessive sugar-sweetened beverage consumption and obesity. Shorter leukocyte telomere length may be an indicator of future obesity risk in high-risk populations as it is particularly sensitive to damage from oxidative stress exposure, including those from sugar-sweetened beverages. © 2017 World Obesity Federation.

  11. The role of heat shock protein 70 in mediating age-dependent mortality in sepsis.

    Science.gov (United States)

    McConnell, Kevin W; Fox, Amy C; Clark, Andrew T; Chang, Nai-Yuan Nicholas; Dominguez, Jessica A; Farris, Alton B; Buchman, Timothy G; Hunt, Clayton R; Coopersmith, Craig M

    2011-03-15

    Sepsis is primarily a disease of the aged, with increased incidence and mortality occurring in aged hosts. Heat shock protein (HSP) 70 plays an important role in both healthy aging and the stress response to injury. The purpose of this study was to determine the role of HSP70 in mediating mortality and the host inflammatory response in aged septic hosts. Sepsis was induced in both young (6- to 12-wk-old) and aged (16- to 17-mo-old) HSP70(-/-) and wild-type (WT) mice to determine whether HSP70 modulated outcome in an age-dependent fashion. Young HSP70(-/-) and WT mice subjected to cecal ligation and puncture, Pseudomonas aeruginosa pneumonia, or Streptococcus pneumoniae pneumonia had no differences in mortality, suggesting HSP70 does not mediate survival in young septic hosts. In contrast, mortality was higher in aged HSP70(-/-) mice than aged WT mice subjected to cecal ligation and puncture (p = 0.01), suggesting HSP70 mediates mortality in sepsis in an age-dependent fashion. Compared with WT mice, aged septic HSP70(-/-) mice had increased gut epithelial apoptosis and pulmonary inflammation. In addition, HSP70(-/-) mice had increased systemic levels of TNF-α, IL-6, IL-10, and IL-1β compared with WT mice. These data demonstrate that HSP70 is a key determinant of mortality in aged, but not young hosts in sepsis. HSP70 may play a protective role in an age-dependent response to sepsis by preventing excessive gut apoptosis and both pulmonary and systemic inflammation.

  12. Henoch-Schönlein purpura in children: its relation to oral and to oral and oral and dental health

    Directory of Open Access Journals (Sweden)

    Arlette Suzy Puspa Pertiwi

    2012-09-01

    Full Text Available > Background: Henoch-Schönlein purpura (HSP is a rare systemic small vessel vasculitis, which commonly occur in childrenbetween 2 and 10 years of age. The course of the disease is often self-limiting, although may manifest long-term renal morbidity. Theseverity of renal involvement decides about the prognosis of this disease. Many factors can trigger the disease attack, which is the mostcommon is bacterial invasion. Since the oral cavity is often refer as infectious foci to other part of the body, it seemed rationally tobe part that contribute the course of disease, thus management of these infectious foci, if possible, gives rise to an astoundingly goodprognosis. Purpose: This paper will describe a review on HSP and the possible association with oral and dental health since it mightbe related to the prognosis of HSP. reviews: Rashes in children are common; they may develop a rash after prescription of antibiotics.Nevertheless there are some childhood diseases that may manifest a rash presentation, such as HSP. It is important for pediatric dentistto have knowledge about HSP and consider the possibility of dental treatment or disease as potential triggers. Conclusion: Oral anddental condition may be the trigger cause of HSP attack. Therefore, it is important for pediatric dental practitioner to be aware of thecourse of the disease in order to limit the expanding complications.> latar belakang: Henoch-Schönlein purpura (HSP merupakan vaskulitis pembuluh darah kecil sistemik yang jarang terjadi danbiasanya menyerang anak usia 2 hingga 10 tahun. Penyakit tersebut seringkali dapat sembuh sendiri, tetapi pada jangka panjangdapat bermanifestasi dengan morbiditas ginjal. Keparahan keterlibatan ginjal menentukan prognosis penyakit. Banyak faktor yangdapat memicu serangan penyakit, tersering adalah invasi bakteri. Karena rongga mulut sering kali merupakan fokus infeksi terhadapbagian lain dari tubuh, maka mempunyai peluang sebagai faktor pemicu

  13. Promoting Active Aging in Russia : Working Longer and More Productively

    OpenAIRE

    Levin, Victoria

    2015-01-01

    A shrinking working-age population will be the Russian Federations biggest demographic challenge in coming decades. With workers increasingly scarce, sustainable future economic development depends on Russias ability to bring into the labor force currently under-utilized groups, such as young mothers and older people, and to maximize the productivity of every worker. This study assesses th...

  14. The advanced glycation end-product Nϵ -carboxymethyllysine promotes progression of pancreatic cancer: implications for diabetes-associated risk and its prevention.

    Science.gov (United States)

    Menini, Stefano; Iacobini, Carla; de Latouliere, Luisa; Manni, Isabella; Ionta, Vittoria; Blasetti Fantauzzi, Claudia; Pesce, Carlo; Cappello, Paola; Novelli, Francesco; Piaggio, Giulia; Pugliese, Giuseppe

    2018-03-13

    Diabetes is an established risk factor for pancreatic cancer (PaC), together with obesity, a Western diet, and tobacco smoking. The common mechanistic link might be the accumulation of advanced glycation end-products (AGEs), which characterizes all of the above disease conditions and unhealthy habits. Surprisingly, however, the role of AGEs in PaC has not been examined yet, despite the evidence of a tumour-promoting role of receptor for advanced glycation end-products (RAGE), the receptor for AGEs. Here, we tested the hypothesis that AGEs promote PaC through RAGE activation. To this end, we investigated the effects of the AGE N ϵ -carboxymethyllysine (CML) in human pancreatic ductal adenocarcinoma (PDA) cell lines and in a mouse model of Kras-driven PaC interbred with a bioluminescent model of proliferation. Tumour growth was monitored in vivo by bioluminescence imaging and confirmed by histology. CML promoted PDA cell growth and RAGE expression, in a concentration-dependent and time-dependent manner, and activated downstream tumourigenic signalling pathways. These effects were counteracted by RAGE antagonist peptide (RAP). Exogenous AGE administration to PaC-prone mice induced RAGE upregulation in pancreatic intraepithelial neoplasias (PanINs) and markedly accelerated progression to invasive PaC. At 11 weeks of age (6 weeks of CML treatment), PaC was observed in eight of 11 (72.7%) CML-treated versus one of 11 (9.1%) vehicle-treated [control (Ctr)] mice. RAP delayed PanIN development in Ctr mice but failed to prevent PaC promotion in CML-treated mice, probably because of competition with soluble RAGE for binding to AGEs and/or compensatory upregulation of the RAGE homologue CD166/ activated leukocyte cell adhesion molecule, which also favoured tumour spread. These findings indicate that AGEs modulate the development and progression of PaC through receptor-mediated mechanisms, and might be responsible for the additional risk conferred by diabetes and other

  15. Maturity Status Strongly Influences the Relative Age Effect in International Elite Under-9 Soccer

    Directory of Open Access Journals (Sweden)

    Lisa Müller, Josef Gehmaier, Christoph Gonaus, Christian Raschner, Erich Müller

    2018-06-01

    Full Text Available The aim of the study was to assess the role of the relative age effect (RAE and to investigate the influence of the biological maturity status on the RAE in international under-9 soccer. The birth dates of 222 male participants of the U9 Eurochampionship Soccer Tournament in Vienna in 2016 were analyzed and divided into four relative age quarters (Q1-Q4 and the biological maturity status was assessed with the age at peak height velocity (APHV method. Based on the mean±standard deviation of the APHV, the athletes were divided into three groups of maturity: early, normal and late maturing. Chi-Square-tests were used to assess the difference between the observed and the expected even relative age quarter distribution and to evaluate the difference between the observed distribution of early, normal and late maturing athletes and the expected normal distribution. A univariate analysis of variance was performed to assess differences in the APHV between the relative age quarters. A RAE was present (χ2 = 23.87; p < 0.001; ω = 0.33. A significant difference was found in APHV between the four relative age quarters (F = 9.906; p < 0.001; relatively older athletes were significantly less mature. A significant difference was found between the distribution of early, normal and late maturing athletes and the expected normal distribution for athletes of Q1 (high percentage of late maturing athletes: 27%; χ2 = 17.69; p < 0.001; ω = 0.46 and of Q4 (high percentage of early maturing soccer players: 31%; χ2 = 12.08; p = 0.002; ω = 0.58. These findings demonstrated that the selection process in international soccer, with athletes younger than 9 years, seems to be associated with the biological maturity status and the relative age. Relatively younger soccer players seem to have a better chance for selection for international tournaments, if they enter puberty at an earlier age, whereas relatively older athletes seem to have an increased likelihood for

  16. 29 CFR 570.9 - States in which State certificates of age are accepted.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false States in which State certificates of age are accepted. 570.9 Section 570.9 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS CHILD LABOR REGULATIONS, ORDERS AND STATEMENTS OF INTERPRETATION Certificates of...

  17. Dependency of cardiovascular risk on reproductive stages and on age among middle-aged Chinese women.

    Science.gov (United States)

    Sun, Y; Ruan, X; Mueck, A O

    2017-10-01

    To assess the 10-year cardiovascular risk in middle-aged Chinese women living in the same community and the impact of reproductive aging and age. This was a cross-sectional study in the Yuetan Community of Beijing. Data on lifestyle habits, prevalence and treatment of chronic diseases with significance for cardiovascular disease (CVD) development were collected by interview. CVD risk factors were assessed by physical examination and laboratory tests. The 10-year cardiovascular risk was calculated using the Framingham 10-year risk score. STRAW +10 criteria were used for the stages of reproductive aging. A total of 536 women, aged 40-60 years, were enrolled. The incidences of hypertension, dyslipidemia, abdominal obesity, glucose intolerance and diabetes were 32.6%, 45.7%, 65.5%, 37.9% and 10.1%, respectively. After adjustment, the incidence of hypertension and diabetes increased with age and with reproductive aging. Dyslipidemia and glucose intolerance were only associated with age. Abdominal obesity was related neither to age nor to reproductive aging. The 10-year cardiovascular risk ranged from 1% to 24.8%; 11.6% of women had a moderate or high Framingham 10-year risk score. CVD risk factors were frequent and more than 10% of the women were at moderate or high risk of developing cardiovascular disease within the next 10 years. To our knowledge, this was demonstrated for the first time in middle-aged Chinese women. Thus, women should maintain a healthy lifestyle and physicians should monitor them to prevent CVD.

  18. Targeted Local Support Vector Machine for Age-Dependent Classification.

    Science.gov (United States)

    Chen, Tianle; Wang, Yuanjia; Chen, Huaihou; Marder, Karen; Zeng, Donglin

    2014-09-01

    We develop methods to accurately predict whether pre-symptomatic individuals are at risk of a disease based on their various marker profiles, which offers an opportunity for early intervention well before definitive clinical diagnosis. For many diseases, existing clinical literature may suggest the risk of disease varies with some markers of biological and etiological importance, for example age. To identify effective prediction rules using nonparametric decision functions, standard statistical learning approaches treat markers with clear biological importance (e.g., age) and other markers without prior knowledge on disease etiology interchangeably as input variables. Therefore, these approaches may be inadequate in singling out and preserving the effects from the biologically important variables, especially in the presence of potential noise markers. Using age as an example of a salient marker to receive special care in the analysis, we propose a local smoothing large margin classifier implemented with support vector machine (SVM) to construct effective age-dependent classification rules. The method adaptively adjusts age effect and separately tunes age and other markers to achieve optimal performance. We derive the asymptotic risk bound of the local smoothing SVM, and perform extensive simulation studies to compare with standard approaches. We apply the proposed method to two studies of premanifest Huntington's disease (HD) subjects and controls to construct age-sensitive predictive scores for the risk of HD and risk of receiving HD diagnosis during the study period.

  19. Age-dependent Fourier model of the shape of the isolated ex vivo human crystalline lens.

    Science.gov (United States)

    Urs, Raksha; Ho, Arthur; Manns, Fabrice; Parel, Jean-Marie

    2010-06-01

    To develop an age-dependent mathematical model of the zero-order shape of the isolated ex vivo human crystalline lens, using one mathematical function, that can be subsequently used to facilitate the development of other models for specific purposes such as optical modeling and analytical and numerical modeling of the lens. Profiles of whole isolated human lenses (n=30) aged 20-69, were measured from shadow-photogrammetric images. The profiles were fit to a 10th-order Fourier series consisting of cosine functions in polar-co-ordinate system that included terms for tilt and decentration. The profiles were corrected using these terms and processed in two ways. In the first, each lens was fit to a 10th-order Fourier series to obtain thickness and diameter, while in the second, all lenses were simultaneously fit to a Fourier series equation that explicitly include linear terms for age to develop an age-dependent mathematical model for the whole lens shape. Thickness and diameter obtained from Fourier series fits exhibited high correlation with manual measurements made from shadow-photogrammetric images. The root-mean-squared-error of the age-dependent fit was 205 microm. The age-dependent equations provide a reliable lens model for ages 20-60 years. The contour of the whole human crystalline lens can be modeled with a Fourier series. Shape obtained from the age-dependent model described in this paper can be used to facilitate the development of other models for specific purposes such as optical modeling and analytical and numerical modeling of the lens. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  20. Age dependent mortality in the pilocarpine model of status epilepticus

    Science.gov (United States)

    Blair, Robert E.; Deshpande, Laxmikant S.; Holbert, William H.; Churn, Severn B.; DeLorenzo, Robert J.

    2010-01-01

    Status epilepticus (SE) is an acute neurological emergency associated with significant morbidity and mortality. Age has been shown to be a critical factor in determining outcome after SE. Understanding the causes of this increased mortality with aging by developing an animal model to study this condition would play a major role in studying mechanisms to limit the mortality due to SE. Here we employed pilocarpine to induce SE in rats aged between 5 to 28 weeks. Similar to clinical studies in man, we observed that age was a significant predictor of mortality following SE. While no deaths were observed in 5-week old animals, mortality due to SE increased progressively with age and reached 90% in 28-week old animals. There was no correlation between the age of animals and severity of SE. With increasing age mortality occurred earlier after the onset of SE. These results indicate that pilocarpine-induced SE in the rat provides a useful model to study age-dependent SE-induced mortality and indicates the importance of using animal models to elucidate the mechanisms contributing to SE-induced mortality and the development of novel therapeutic interventions to prevent SE-induced death. PMID:19429042

  1. Age-dependent mortality in the pilocarpine model of status epilepticus.

    Science.gov (United States)

    Blair, Robert E; Deshpande, Laxmikant S; Holbert, William H; Churn, Severn B; DeLorenzo, Robert J

    2009-04-10

    Status epilepticus (SE) is an acute neurological emergency associated with significant morbidity and mortality. Age has been shown to be a critical factor in determining outcome after SE. Understanding the causes of this increased mortality with aging by developing an animal model to study this condition would play a major role in studying mechanisms to limit the mortality due to SE. Here we employed pilocarpine to induce SE in rats aged between 5 and 28 weeks. Similar to clinical studies in man, we observed that age was a significant predictor of mortality following SE. While no deaths were observed in 5-week-old animals, mortality due to SE increased progressively with age and reached 90% in 28-week-old animals. There was no correlation between the age of animals and severity of SE. With increasing age mortality occurred earlier after the onset of SE. These results indicate that pilocarpine-induced SE in the rat provides a useful model to study age-dependent SE-induced mortality and indicates the importance of using animal models to elucidate the mechanisms contributing to SE-induced mortality and the development of novel therapeutic interventions to prevent SE-induced death.

  2. Anomalous scaling in an age-dependent branching model

    OpenAIRE

    Keller-Schmidt, Stephanie; Tugrul, Murat; Eguiluz, Victor M.; Hernandez-Garcia, Emilio; Klemm, Konstantin

    2010-01-01

    We introduce a one-parametric family of tree growth models, in which branching probabilities decrease with branch age $\\tau$ as $\\tau^{-\\alpha}$. Depending on the exponent $\\alpha$, the scaling of tree depth with tree size $n$ displays a transition between the logarithmic scaling of random trees and an algebraic growth. At the transition ($\\alpha=1$) tree depth grows as $(\\log n)^2$. This anomalous scaling is in good agreement with the trend observed in evolution of biological species, thus p...

  3. Cross-talk between an activator of nuclear receptors-mediated transcription and the D1 dopamine receptor signaling pathway.

    Science.gov (United States)

    Schmidt, Azriel; Vogel, Robert; Rutledge, Su Jane; Opas, Evan E; Rodan, Gideon A; Friedman, Eitan

    2005-03-01

    Nuclear receptors are transcription factors that usually interact, in a ligand-dependent manner, with specific DNA sequences located within promoters of target genes. The nuclear receptors can also be controlled in a ligand-independent manner via the action of membrane receptors and cellular signaling pathways. 5-Tetradecyloxy-2-furancarboxylic acid (TOFA) was shown to stimulate transcription from the MMTV promoter via chimeric receptors that consist of the DNA binding domain of GR and the ligand binding regions of the PPARbeta or LXRbeta nuclear receptors (GR/PPARbeta and GR/LXRbeta). TOFA and hydroxycholesterols also modulate transcription from NF-kappaB- and AP-1-controlled reporter genes and induce neurite differentiation in PC12 cells. In CV-1 cells that express D(1) dopamine receptors, D(1) dopamine receptor stimulation was found to inhibit TOFA-stimulated transcription from the MMTV promoter that is under the control of chimeric GR/PPARbeta and GR/LXRbeta receptors. Treatment with the D(1) dopamine receptor antagonist, SCH23390, prevented dopamine-mediated suppression of transcription, and by itself increased transcription controlled by GR/LXRbeta. Furthermore, combined treatment of CV-1 cells with TOFA and SCH23390 increased transcription controlled by the GR/LXRbeta chimeric receptor synergistically. The significance of this in vitro synergy was demonstrated in vivo, by the observation that SCH23390 (but not haloperidol)-mediated catalepsy in rats was potentiated by TOFA, thus showing that an agent that mimics the in vitro activities of compounds that activate members of the LXR and PPAR receptor families can influence D1 dopamine receptor elicited responses.

  4. COX2 inhibition during nephrogenic period induces ANG II hypertension and sex-dependent changes in renal function during aging.

    Science.gov (United States)

    Reverte, Virginia; Tapia, Antonio; Loria, Analia; Salazar, Francisco; Llinas, M Teresa; Salazar, F Javier

    2014-03-01

    This study was performed to test the hypothesis that ANG II contributes to the hypertension and renal functional alterations induced by a decrease of COX2 activity during the nephrogenic period. It was also examined whether renal functional reserve and renal response to volume overload and high sodium intake are reduced in 3-4- and 9-11-mo-old male and female rats treated with vehicle or a COX2 inhibitor during nephrogenic period (COX2np). Our data show that this COX2 inhibition induces an ANG II-dependent hypertension that is similar in male and female rats. Renal functional reserve is reduced in COX2np-treated rats since their renal response to an increase in plasma amino acids levels is abolished, and their renal ability to eliminate a sodium load is impaired (P renal excretory ability is similar in both sexes during aging but does not induce the development of a sodium-sensitive hypertension. However, the prolonged high-sodium intake at 9-11 mo of age leads to a greater proteinuria in male than in female (114 ± 12 μg/min vs. 72 ± 8 μg/min; P Renal hemodynamic sensitivity to acute increments in ANG II is unaltered in both sexes and at both ages in COX2np-treated rats. In summary, these results indicate that the reduction of COX2 activity during nephrogenic period programs for the development of an ANG II-dependent hypertension, reduces renal functional reserve to a similar extent in both sexes, and increases proteinuria in males but not in females when there is a prolonged increment in sodium intake.

  5. Yeast chronological lifespan and proteotoxic stress: is autophagy good or bad?

    Science.gov (United States)

    Sampaio-Marques, Belém; Felgueiras, Carolina; Silva, Alexandra; Rodrigues, Fernando; Ludovico, Paula

    2011-10-01

    Autophagy, a highly conserved proteolytic mechanism of quality control, is essential for the maintenance of metabolic and cellular homoeostasis and for an efficient cellular response to stress. Autophagy declines with aging and is believed to contribute to different aspects of the aging phenotype. The nutrient-sensing pathways PKA (protein kinase A), Sch9 and TOR (target of rapamycin), involved in the regulation of yeast lifespan, also converge on a common targeted process: autophagy. The molecular mechanisms underlying the regulation of autophagy and aging by these signalling pathways in yeast, with special attention to the TOR pathway, are discussed in the present paper. The question of whether or not autophagy could contribute to yeast cell death occurring during CLS (chronological lifespan) is discussed in the light of our findings obtained after autophagy activation promoted by proteotoxic stress. Autophagy progressively increases in cells expressing the aggregation-prone protein α-synuclein and seems to participate in the early cell death and shortening of CLS under these conditions, highlighting that autophagic activity should be maintained below physiological levels to exert its promising anti-aging effects.

  6. Stability analysis of nonlinear integro-differential equations arising in age-dependent epidemic models

    International Nuclear Information System (INIS)

    El Doma, M.

    1995-05-01

    An age-structured epidemic model of an SI type that incorporate vertical transmission is investigated when the fertility and mortality rates depend on age. We determine the steady states and examine their stabilities. (author). 13 refs

  7. Henoch-Schönlein purpura without systemic involvement beginning with acute scrotum and mimicking torsion of testis

    Directory of Open Access Journals (Sweden)

    Levent Verim

    2013-04-01

    Full Text Available Henoch-Schönlein purpura (HSP is the most common systemic vasculitis in children. Typical presentations of HSP are palpable purpura of the small vessels in the hips and lower limbs, abdominal pain, arthritis, and hematuria. Scrotal involvement manifested by the presence of scrotal pain and swelling during the course of the disease is rarely seen. HSP without systemic involvement with acute scrotum mimicking testicular torsion is even rare in the medical literature. In most cases, patients with this disease achieve complete recovery. Herein, we report an interesting HSP case with skin symptoms but without systemic involvement and then progression to acute scrotum resembling torsion of testis.

  8. Chronic administration during early adulthood does not alter the hormonally-dependent disruptive effects of delta-9-tetrahydrocannabinol (Δ9-THC) on complex behavior in female rats.

    Science.gov (United States)

    Winsauer, Peter J; Sutton, Jessie L

    2014-02-01

    This study examined whether chronic Δ(9)-THC during early adulthood would produce the same hormonally-dependent deficits in learning that are produced by chronic Δ(9)-THC during adolescence. To do this, either sham-operated (intact) or ovariectomized (OVX) female rats received daily saline or 5.6 mg/kg of Δ(9)-THC i.p. for 40 days during early adulthood. Following chronic administration, and a drug-free period to train both a learning and performance task, acute dose-effect curves for Δ(9)-THC (0.56-10 mg/kg) were established in each of the four groups (intact/saline, intact/THC, OVX/saline and OVX/THC). The dependent measures of responding under the learning and performance tasks were the overall response rate and the percentage of errors. Although the history of OVX and chronic Δ(9)-THC in early adulthood did not significantly affect non-drug or baseline behavior under the tasks, acute administration of Δ(9)-THC produced both rate-decreasing and error-increasing effects on learning and performance behavior, and these effects were dependent on their hormone condition. More specifically, both intact groups were more sensitive to the rate-decreasing and error-increasing effects of Δ(9)-THC than the OVX groups irrespective of chronic Δ(9)-THC administration, as there was no significant main effect of chronic treatment and no significant interaction between chronic treatment (saline or Δ(9)-THC) and the dose of Δ(9)-THC administered as an adult. Post mortem examination of 10 brain regions also indicated there were significant differences in agonist-stimulated GTPγS binding across brain regions, but no significant effects of chronic treatment and no significant interaction between the chronic treatment and cannabinoid signaling. Thus, acute Δ(9)-THC produced hormonally-dependent effects on learning and performance behavior, but a period of chronic administration during early adulthood did not alter these effects significantly, which is contrary to what we

  9. Synergistic Effect of Rapamycin and Metformin Against Age-Dependent Oxidative Stress in Rat Erythrocytes.

    Science.gov (United States)

    Singh, Abhishek Kumar; Garg, Geetika; Singh, Sandeep; Rizvi, Syed Ibrahim

    2017-10-01

    Erythrocytes are particularly vulnerable toward age-dependent oxidative stress-mediated damage. Caloric restriction mimetics (CRMs) may provide a novel strategy for the maintenance of redox balance as well as effective treatment of age-associated diseases. Herein, we have investigated the beneficial effect of cotreatment with CRM-candidate drugs, rapamycin (an immunosuppressant drug and inhibitor of mammalian target of rapamycin) and metformin (an antidiabetic biguanide and activator of adenosine monophosphate kinase), against aging-induced oxidative stress in erythrocytes and plasma of aging rats. Male Wistar rats of age 4 (young) and 24 months (old) were coexposed to rapamycin (0.5 mg/kg body weight [b.w.]) and metformin (300 mg/kg b.w.), and data were compared with the response of rats receiving an independent exposure to these chemicals at similar doses. The exposure of individual candidate drugs significantly reversed the age-dependent alterations in the endpoints associated with oxidative stress such as reactive oxygen species, ferric reducing ability of plasma, malondialdehyde, reduced glutathione, plasma membrane redox system, plasma protein carbonyl, and acetyl cholinesterase in erythrocytes and plasma of aging rats. However, the cotreatment with rapamycin and metformin showed a significant augmented effect compared with individual drug interventions on reversal of these age-dependent biomarkers of oxidative stress, suggesting a synergistic response. Thus, the findings open up further possibilities for the design of new combinatorial therapies to prevent oxidative stress- and age-associated health problems.

  10. Arid5b facilitates chondrogenesis by recruiting the histone demethylase Phf2 to Sox9-regulated genes

    Science.gov (United States)

    Hata, Kenji; Takashima, Rikako; Amano, Katsuhiko; Ono, Koichiro; Nakanishi, Masako; Yoshida, Michiko; Wakabayashi, Makoto; Matsuda, Akio; Maeda, Yoshinobu; Suzuki, Yutaka; Sugano, Sumio; Whitson, Robert H.; Nishimura, Riko; Yoneda, Toshiyuki

    2013-11-01

    Histone modification, a critical step for epigenetic regulation, is an important modulator of biological events. Sox9 is a transcription factor critical for endochondral ossification; however, proof of its epigenetic regulation remains elusive. Here we identify AT-rich interactive domain 5b (Arid5b) as a transcriptional co-regulator of Sox9. Arid5b physically associates with Sox9 and synergistically induces chondrogenesis. Growth of Arid5b-/- mice is retarded with delayed endochondral ossification. Sox9-dependent chondrogenesis is attenuated in Arid5b-deficient cells. Arid5b recruits Phf2, a histone lysine demethylase, to the promoter region of Sox9 target genes and stimulates H3K9me2 demethylation of these genes. In the promoters of chondrogenic marker genes, H3K9me2 levels are increased in Arid5b-/- chondrocytes. Finally, we show that Phf2 knockdown inhibits Sox9-induced chondrocyte differentiation. Our findings establish an epigenomic mechanism of skeletal development, whereby Arid5b promotes chondrogenesis by facilitating Phf2-mediated histone demethylation of Sox9-regulated chondrogenic gene promoters.

  11. Age-dependent risk-based methodology and its application to prioritization of nuclear power plant components and to maintenance for managing aging using PRAs

    International Nuclear Information System (INIS)

    Levy, I.S.; Vesely, W.E.

    1990-01-01

    This paper is based on a study to demonstrate several important ways that the age-dependent risk-based methodology developed by the Nuclear Plant Aging Research (NPAR) Program may be applied to resolving important issues related to the aging of nuclear power plant systems, structures, and components (SSCs). The study was sponsored by the NPAR Program of the Division of Engineering, Office of Nuclear Regulatory Research of the U.S. Nuclear Regulatory Commission (NRC). Initiated on the basis of a Users Need Request, the age-dependent risk-based methodology has been under development by the NPAR Program for several years. In this methodology, the time-dependent change in a component's risk contribution is the product of two factors: (1) the risk importance of the component (e.g., the change in its risk contribution when it is assumed to be totally unavailable to perform its intended safety function) and (2) the change in its unavailability with time. This change in the component's unavailability with time is a function of the component's aging rate and plant inspection and maintenance practices. The methodology permits evaluations of the age-dependent risk contributions from both single- and multiple-components. Principal results and conclusions generated by the methodology demonstrations are discussed

  12. The Frequency-Dependent Aerobic Exercise Effects of Hypothalamic GABAergic Expression and Cardiovascular Functions in Aged Rats

    Directory of Open Access Journals (Sweden)

    Yan Li

    2017-06-01

    Full Text Available A decline in cardiovascular modulation is a feature of the normal aging process and associated with cardiovascular diseases (CVDs such as hypertension and stroke. Exercise training is known to promote cardiovascular adaptation in young animals and positive effects on motor and cognitive capabilities, as well as on brain plasticity for all ages in mice. Here, we examine the question of whether aerobic exercise interventions may impact the GABAergic neurons of the paraventricular nucleus (PVN in aged rats which have been observed to have a decline in cardiovascular integration function. In the present study, young (2 months and old (24 months male Wistar rats were divided into young control (YC, old sedentary, old low frequency exercise (20 m/min, 60 min/day, 3 days/week, 12 weeks and old high frequency exercise (20 m/min, 60 min/day, 5 days/week, 12 weeks. Exercise training indexes were obtained, including resting heart rate (HR, blood pressure (BP, plasma norepinephrine (NE, and heart weight (HW-to-body weight (BW ratios. The brain was removed and processed according to the immunofluorescence staining and western blot used to analyze the GABAergic terminal density, the proteins of GAD67, GABAA receptor and gephyrin in the PVN. There were significant changes in aged rats compared with those in the YC. Twelve weeks aerobic exercise training has volume-dependent ameliorated effects on cardiovascular parameters, autonomic nervous activities and GABAergic system functions. These data suggest that the density of GABAergic declines in the PVN is associated with imbalance in autonomic nervous activities in normal aging. Additionally, aerobic exercise can rescue aging-related an overactivity of the sympathetic nervous system and induces modifications the resting BP and HR to lower values via improving the GABAergic system in the PVN.

  13. The Frequency-Dependent Aerobic Exercise Effects of Hypothalamic GABAergic Expression and Cardiovascular Functions in Aged Rats

    Science.gov (United States)

    Li, Yan; Zhao, Ziqi; Cai, Jiajia; Gu, Boya; Lv, Yuanyuan; Zhao, Li

    2017-01-01

    A decline in cardiovascular modulation is a feature of the normal aging process and associated with cardiovascular diseases (CVDs) such as hypertension and stroke. Exercise training is known to promote cardiovascular adaptation in young animals and positive effects on motor and cognitive capabilities, as well as on brain plasticity for all ages in mice. Here, we examine the question of whether aerobic exercise interventions may impact the GABAergic neurons of the paraventricular nucleus (PVN) in aged rats which have been observed to have a decline in cardiovascular integration function. In the present study, young (2 months) and old (24 months) male Wistar rats were divided into young control (YC), old sedentary, old low frequency exercise (20 m/min, 60 min/day, 3 days/week, 12 weeks) and old high frequency exercise (20 m/min, 60 min/day, 5 days/week, 12 weeks). Exercise training indexes were obtained, including resting heart rate (HR), blood pressure (BP), plasma norepinephrine (NE), and heart weight (HW)-to-body weight (BW) ratios. The brain was removed and processed according to the immunofluorescence staining and western blot used to analyze the GABAergic terminal density, the proteins of GAD67, GABAA receptor and gephyrin in the PVN. There were significant changes in aged rats compared with those in the YC. Twelve weeks aerobic exercise training has volume-dependent ameliorated effects on cardiovascular parameters, autonomic nervous activities and GABAergic system functions. These data suggest that the density of GABAergic declines in the PVN is associated with imbalance in autonomic nervous activities in normal aging. Additionally, aerobic exercise can rescue aging-related an overactivity of the sympathetic nervous system and induces modifications the resting BP and HR to lower values via improving the GABAergic system in the PVN. PMID:28713263

  14. Dependence of absolute magnitudes (energies) of flares on the cluster age containing flare stars

    International Nuclear Information System (INIS)

    Parsamyan, Eh.S.

    1976-01-01

    Dependences between Δmsub(u) and msub(u) are given for the Orion, NGC 7000, Pleiades and Praesepe aggregations. Maximum absolute values of flares have been calculated for stars with different luminosities. It has been shown that the values of flares can be limited by a straight line which gives the representation on the distribution of maximum values of amplitudes for the stars with different luminosities in an aggregation. Presented are k and m 0 parameters characterizing the lines fot the Orion, NGC 7000, Pleiades and Praesepe aggregation and their age T dependence. From the dependence between k (angular coefficient of straight lines) and lgT for the aggregation with known T the age of those aggregation involving a great amount of flaring stars can be found. The age of flaring stars in the neighbourhood of the Sun has been determined. The age of UV Ceti has been shown by an order to exceed that of the rest stars

  15. Thyroid Function among Breastfed Children with Chronically Excessive Iodine Intakes

    Directory of Open Access Journals (Sweden)

    Inger Aakre

    2016-06-01

    Full Text Available Iodine excess may impair thyroid function and trigger adverse health consequences for children. This study aims to describe iodine status among breastfed infants with high iodine exposure in the Saharawi refugee camps Algeria, and further assess thyroid function and iodine status among the children three years later. In 2010, a cross-sectional study among 111 breastfed children aged 0–6 months was performed (baseline study. In 2013, a second cross-sectional study (follow-up study was conducted among 289 children; 213 newly selected and 76 children retrieved from baseline. Urinary iodine concentration (UIC and breast milk iodine concentration (BMIC were measured at baseline. UIC, thyroid hormones and serum thyroglobulin (Tg were measured at follow-up. At baseline and follow-up, 88% and 72% had excessive iodine intakes (UIC ≥ 300 µg/L, respectively. At follow-up, 24% had a thyroid hormone disturbance and/or elevated serum Tg, including 9% with subclinical hypothyroidism (SCH, 4% with elevated fT3 and 14% with elevated Tg. Children with SCH had poorer linear growth and were more likely to be underweight than the children without SCH. Excessive iodine intakes and thyroid disturbances were common among children below four years of age in our study. Further, SCH seemed to be associated with poor growth and weight.

  16. Age-dependent dose coefficients for tritium in Asian populations

    Energy Technology Data Exchange (ETDEWEB)

    Trivedi, A

    1999-10-01

    The International Commission on Radiological Protection (ICRP) Publications 56 (1989) and 67 (1993) have prescribed the biokinetic models and age-dependent dose coefficients for tritiated water and organically bound tritium. The dose coefficients are computed from values selected to specify the anatomical, morphological and physiological characteristics of a three-month-old, one-year-old, five-year-old, 10-year-old, 15-year-old and adult (Reference Man) Caucasian living in North America and Western Europe. However, values for Reference Man and other age groups are not directly applicable to Asians, because of differences in race, custom, dietary habits and climatic conditions. An Asian Man model, including five age groups, has been proposed by Tanaka and Kawamura (1996, 1998) for use in internal dosimetry. The basic concept of the ICRP Reference Man and the system describing body composition in ICRP Publication 23 (1975) were used. Reference values for Asians were given for the body weight and height, the mass of soft tissue, the mass of body water and the daily fluid balance, and are used to compute the dose coefficients for tritium. The age-dependent dose coefficients for Asians for tritiated water intakes are smaller by 20 to 30% of the currently prescribed values (Trivedi, 1998). The reduction in the dose coefficient values is caused by the increased daily fluid balance among Asians. The dose coefficient for tritiated water is 1.4 x 10{sup -11} Sv Bq{sup -1} for Asian Man compared to 2.0 x 10{sup -11} Sv Bq{sup -1} for Reference Man. The dose coefficients for organically bound tritium are only marginally different from those of the ICRP values. The dose coefficient for organically bound tritium for Asian Man is 4.0 x 10{sup -11} Sv Bq{sup -11} compared to 4.6 x 10{sup -11} Sv Bq{sup -1} for Reference Man. (author)

  17. Age-dependent dose coefficients for tritium in Asian populations

    International Nuclear Information System (INIS)

    Trivedi, A.

    1999-10-01

    The International Commission on Radiological Protection (ICRP) Publications 56 (1989) and 67 (1993) have prescribed the biokinetic models and age-dependent dose coefficients for tritiated water and organically bound tritium. The dose coefficients are computed from values selected to specify the anatomical, morphological and physiological characteristics of a three-month-old, one-year-old, five-year-old, 10-year-old, 15-year-old and adult (Reference Man) Caucasian living in North America and Western Europe. However, values for Reference Man and other age groups are not directly applicable to Asians, because of differences in race, custom, dietary habits and climatic conditions. An Asian Man model, including five age groups, has been proposed by Tanaka and Kawamura (1996, 1998) for use in internal dosimetry. The basic concept of the ICRP Reference Man and the system describing body composition in ICRP Publication 23 (1975) were used. Reference values for Asians were given for the body weight and height, the mass of soft tissue, the mass of body water and the daily fluid balance, and are used to compute the dose coefficients for tritium. The age-dependent dose coefficients for Asians for tritiated water intakes are smaller by 20 to 30% of the currently prescribed values (Trivedi, 1998). The reduction in the dose coefficient values is caused by the increased daily fluid balance among Asians. The dose coefficient for tritiated water is 1.4 x 10 -11 Sv Bq -1 for Asian Man compared to 2.0 x 10 -11 Sv Bq -1 for Reference Man. The dose coefficients for organically bound tritium are only marginally different from those of the ICRP values. The dose coefficient for organically bound tritium for Asian Man is 4.0 x 10 -11 Sv Bq -11 compared to 4.6 x 10 -11 Sv Bq -1 for Reference Man. (author)

  18. Schönheit und andere Provokationen - Eine neue evolutionsbiologische Theorie der Kunst

    Science.gov (United States)

    Junker, Thomas

    Die Evolution hat viele spektakuläre Phänomene hervorgebracht - von der Eleganz des Vogelflugs über die gigantischen Körper der Dinosaurier und die farbenprächtige Vielfalt der Korallenriffe bis hin zu ihrem jüngsten Geniestreich - der menschlichen Kunst. Die schönen Künste - Malerei, Bildhauerei und Architektur, Theater, Tanz, Oper und Filmkunst, Musik und Literatur - Produkte der Evolution? Diese Vorstellung mutet vielen Menschen fremd an, aber wie könnte es anders sein? Denn wenn Charles Darwin recht hat, dann sind nicht nur die körperlichen Merkmale der Menschen als Antworten auf die Erfordernisse des Lebens entstanden, sondern auch ihre geistigen Fähigkeiten und Verhaltensweisen. Im Jahr 1859 hatte er auf den letzten Seiten seines berühmten Buches über die Entstehung der Arten eine kühne Prophezeiung gemacht: Durch die Evolutionstheorie werde es "zu einer bemerkenswerten Revolution in der Naturwissenschaft kommen […]. Die Psychologie wird auf die neue Grundlage gestellt, dass jede geistige Kraft und Fähigkeit notwendigerweise durch graduelle Übergänge erworben wird“ (Darwin 1859, S. 484, 488; Junker 2008).

  19. Active Aging Promotion: Results from the Vital Aging Program

    OpenAIRE

    Caprara, Mariagiovanna; Molina, María Ángeles; Schettini, Rocío; Santacreu, Marta; Orosa, Teresa; Mendoza-Núñez, Víctor Manuel; Rojas, Macarena; Fernández-Ballesteros, Rocío

    2013-01-01

    Active aging is one of the terms in the semantic network of aging well, together with others such as successful, productive, competent aging. All allude to the new paradigm in gerontology, where by aging is considered from a positive perspective. Most authors in the field agree active aging is a multidimensional concept, embracing health, physical and cognitive fitness, positive affect and control, social relationships and engagement. This paper describes Vital Aging, an individual activ...

  20. Hypomethylation of IL17RC Promoter Associates with Age-related Macular Degeneration

    Science.gov (United States)

    Wei, Lai; Liu, Baoying; Tuo, Jingsheng; Shen, Defen; Chen, Ping; Li, Zhiyu; Liu, Xunxian; Ni, Jia; Dagur, Pradeep; Sen, H. Nida; Jawad, Shayma; Ling, Diamond; Park, Stanley; Chakrabarty, Sagarika; Meyerle, Catherine; Agron, Elvira; Ferris, Frederick L.; Chew, Emily Y.; McCoy, J. Philip; Blum, Emily; Francis, Peter J.; Klein, Michael L.; Guymer, Robyn H.; Baird, Paul N.; Chan, Chi-Chao; Nussenblatt, Robert B.

    2012-01-01

    SUMMARY Age related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly population worldwide. While recent studies have demonstrated strong genetic associations of single nucleotide polymorphisms within a number of genes and AMD, other modes of regulation are also likely to play a role in its etiology. We identified a significantly decreased level of methylation on the IL17RC promoter in AMD patients. Further, we showed that hypomethylation of the IL17RC promoter in AMD patients led to an elevated expression of its protein and mRNA in peripheral blood as well as in the affected retina and choroid, suggesting that the DNA methylation pattern and expression of IL17RC may potentially serve as a biomarker for the diagnosis of AMD and likely plays a role in disease pathogenesis. PMID:23177625

  1. The promoter for intestinal cell kinase is head-to-head with F-Box 9 and contains functional sites for TCF7L2 and FOXA factors

    Directory of Open Access Journals (Sweden)

    Cohn Steven M

    2010-05-01

    Full Text Available Abstract Background Intestinal cell kinase (ICK; GeneID 22858 is a conserved MAPK and CDK-like kinase that is widely expressed in human tissues. Data from the Cancer Genome Anatomy Project indicated ICK mRNA is increased in cancer, and that its expression correlated with expression of mRNA for an uncharacterized F-box protein, FBX9 (GeneID: 26268. ICK and FBX9 genes are arranged head-to-head on opposite strands, with start sites for transcription separated by ~3.3 kb. We hypothesized ICK and FBX9 are potentially important genes in cancer controlled by a bidirectional promoter. Results We assessed promoter activity of the intergenic region in both orientations in cancer cell lines derived from breast (AU565, SKBR3, colon (HCT-15, KM12, and stomach (AGS cancers, as well as in embryonic human kidney (HEK293T cells. The intergenic segment was active in both orientations in all of these lines, and ICK promoter activity was greater than FBX9 promoter activity. Results from deletions and truncations defined a minimal promoter for ICK, and revealed that repressors and enhancers differentially regulate ICK versus FBX9 promoter activity. The ICK promoter contains consensus motifs for several FOX-family transcription factors that align when mouse and human are compared using EMBOSS. FOXA1 and FOXA2 increase luciferase activity of a minimal promoter 10-20 fold in HEK293T cells. Consensus sites for TCF7L2 (TCF4 (Gene Id: 6934 are also present in both mouse and human. The expression of β-catenin increased activity of the minimal promoter ~10 fold. ICK reference mRNAs (NM_014920.3, NM_016513 are expressed in low copy number and increased in some breast cancers, using a ten base tag 5'-TCAACCTTAT-3' specific for both ICK transcripts. Conclusion ICK and FBX9 are divergently transcribed from a bidirectional promoter that is GC-rich and contains a CpG island. A minimal promoter for ICK contains functional sites for β-cateinin/TCF7L2 and FOXA. These data are

  2. Studies on the age-dependent proliferation kinetics of the epithelium of the rat small intestine

    International Nuclear Information System (INIS)

    Kranz, D.; Dietze, F.; Laue, R.; Fuhrmann, I.

    1980-01-01

    The small intestine of 244 Wistar rats, aged 6 days, 6 weeks, 6, 12, 23, and 28 months, respectively. were investigated autoradiographically as to their age-dependent cell proliferation kinetics of the mucosal epithelial cells. There were age-dependent differences concerning the hourly regeneration ratio of the crypt cells and the migration velocity of the enterocytes. Both parameters became greater while the existing non growth fraction became smaller with increasing age. The non growth fraction seems to be a reserve being involved into the proliferating pool if required

  3. Chrysin inhibits tumor promoter-induced MMP-9 expression by blocking AP-1 via suppression of ERK and JNK pathways in gastric cancer cells.

    Directory of Open Access Journals (Sweden)

    Yong Xia

    Full Text Available Cell invasion is a crucial mechanism of cancer metastasis and malignancy. Matrix metalloproteinase-9 (MMP-9 is an important proteolytic enzyme involved in the cancer cell invasion process. High expression levels of MMP-9 in gastric cancer positively correlate with tumor aggressiveness and have a significant negative correlation with patients' survival times. Recently, mechanisms suppressing MMP-9 by phytochemicals have become increasingly investigated. Chrysin, a naturally occurring chemical in plants, has been reported to suppress tumor metastasis. However, the effects of chrysin on MMP-9 expression in gastric cancer have not been well studied. In the present study, we tested the effects of chrysin on MMP-9 expression in gastric cancer cells, and determined its underlying mechanism. We examined the effects of chrysin on MMP-9 expression and activity via RT-PCR, zymography, promoter study, and western blotting in human gastric cancer AGS cells. Chrysin inhibited phorbol-12-myristate 13-acetate (PMA-induced MMP-9 expression in a dose-dependent manner. Using AP-1 decoy oligodeoxynucleotides, we confirmed that AP-1 was the crucial transcriptional factor for MMP-9 expression. Chrysin blocked AP-1 via suppression of the phosphorylation of c-Jun and c-Fos through blocking the JNK1/2 and ERK1/2 pathways. Furthermore, AGS cells pretreated with PMA showed markedly enhanced invasiveness, which was partially abrogated by chrysin and MMP-9 antibody. Our results suggest that chrysin may exert at least part of its anticancer effect by controlling MMP-9 expression through suppression of AP-1 activity via a block of the JNK1/2 and ERK1/2 signaling pathways in gastric cancer AGS cells.

  4. 2-HG Inhibits Necroptosis by Stimulating DNMT1-Dependent Hypermethylation of the RIP3 Promoter

    Directory of Open Access Journals (Sweden)

    Zhentao Yang

    2017-05-01

    Full Text Available 2-hydroxyglutarate-(2-HG-mediated inhibition of TET2 activity influences DNA hypermethylation in cells harboring mutations of isocitrate dehydrogenases 1 and 2 (IDH1/2. Here, we show that 2-HG also regulates DNA methylation mediated by DNA methyltransferase 1 (DNMT1. DNMT1-dependent hypermethylation of the RIP3 promoter occurred in both IDH1 R132Q knockin mutant mouse embryonic fibroblast (MEFs and 2-HG-treated wild-type (WT MEFs. We found that 2-HG bound to DNMT1 and stimulated its association with the RIP3 promoter, inducing hypermethylation that reduces RIP3 protein and consequently impaired RIP3-dependent necroptosis. In human glioma samples, RIP3 protein levels correlated negatively with IDH1 R132H levels. Furthermore, ectopic expression of RIP3 in transformed IDH1-mutated MEFs inhibited the growth of tumors derived from these cells following transplantation into nude mice. Thus, our research sheds light on a mechanism of 2-HG-induced DNA hypermethylation and suggests that impaired necroptosis contributes to the tumorigenesis driven by IDH1/2 mutations.

  5. Endogenous bile acid disposition in rat and human sandwich-cultured hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Marion, Tracy L., E-mail: tracylmarion@qualyst.com [Curriculum in Toxicology, UNC School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7270 (United States); Perry, Cassandra H., E-mail: cassandraperry@qualyst.com [Qualyst, Inc., Durham, NC 27713 (United States); St Claire, Robert L., E-mail: bobstclaire@qualyst.com [Qualyst, Inc., Durham, NC 27713 (United States); Brouwer, Kim L.R., E-mail: kbrouwer@unc.edu [Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, CB 7569 Kerr Hall, Chapel Hill, NC 27599-7569 (United States)

    2012-05-15

    Sandwich-cultured hepatocytes (SCH) are used commonly to investigate hepatic transport protein-mediated uptake and biliary excretion of substrates. However, little is known about the disposition of endogenous bile acids (BAs) in SCH. In this study, four endogenous conjugated BAs common to rats and humans [taurocholic acid (TCA), glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), and glycochenodeoxycholic acid (GCDCA)], as well as two BA species specific to rodents (α- and β-tauromuricholic acid; α/β TMCA), were profiled in primary rat and human SCH. Using B-CLEAR{sup ®} technology, BAs were measured in cells + bile canaliculi, cells, and medium of SCH by LC-MS/MS. Results indicated that, just as in vivo, taurine-conjugated BA species were predominant in rat SCH, while glycine-conjugated BAs were predominant in human SCH. Total intracellular BAs remained relatively constant over days in culture in rat SCH. Total BAs in control (CTL) cells + bile, cells, and medium were approximately 3.4, 2.9, and 8.3-fold greater in human than in rat. The estimated intracellular concentrations of the measured total BAs were 64.3 ± 5.9 μM in CTL rat and 183 ± 56 μM in CTL human SCH, while medium concentrations of the total BAs measured were 1.16 ± 0.21 μM in CTL rat SCH and 9.61 ± 6.36 μM in CTL human SCH. Treatment of cells for 24 h with 10 μM troglitazone (TRO), an inhibitor of the bile salt export pump (BSEP) and the Na{sup +}-taurocholate cotransporting polypeptide (NTCP), had no significant effect on endogenous BAs measured at the end of the 24-h culture period, potentially due to compensatory mechanisms that maintain BA homeostasis. These data demonstrate that BAs in SCH are similar to in vivo, and that SCH may be a useful in vitro model to study alterations in BA disposition if species differences are taken into account. -- Highlights: ► Bile acids (BAs) were measured in rat and human sandwich-cultured hepatocytes (SCH). ► Cell and medium BA

  6. Endogenous bile acid disposition in rat and human sandwich-cultured hepatocytes

    International Nuclear Information System (INIS)

    Marion, Tracy L.; Perry, Cassandra H.; St Claire, Robert L.; Brouwer, Kim L.R.

    2012-01-01

    Sandwich-cultured hepatocytes (SCH) are used commonly to investigate hepatic transport protein-mediated uptake and biliary excretion of substrates. However, little is known about the disposition of endogenous bile acids (BAs) in SCH. In this study, four endogenous conjugated BAs common to rats and humans [taurocholic acid (TCA), glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), and glycochenodeoxycholic acid (GCDCA)], as well as two BA species specific to rodents (α- and β-tauromuricholic acid; α/β TMCA), were profiled in primary rat and human SCH. Using B-CLEAR ® technology, BAs were measured in cells + bile canaliculi, cells, and medium of SCH by LC-MS/MS. Results indicated that, just as in vivo, taurine-conjugated BA species were predominant in rat SCH, while glycine-conjugated BAs were predominant in human SCH. Total intracellular BAs remained relatively constant over days in culture in rat SCH. Total BAs in control (CTL) cells + bile, cells, and medium were approximately 3.4, 2.9, and 8.3-fold greater in human than in rat. The estimated intracellular concentrations of the measured total BAs were 64.3 ± 5.9 μM in CTL rat and 183 ± 56 μM in CTL human SCH, while medium concentrations of the total BAs measured were 1.16 ± 0.21 μM in CTL rat SCH and 9.61 ± 6.36 μM in CTL human SCH. Treatment of cells for 24 h with 10 μM troglitazone (TRO), an inhibitor of the bile salt export pump (BSEP) and the Na + -taurocholate cotransporting polypeptide (NTCP), had no significant effect on endogenous BAs measured at the end of the 24-h culture period, potentially due to compensatory mechanisms that maintain BA homeostasis. These data demonstrate that BAs in SCH are similar to in vivo, and that SCH may be a useful in vitro model to study alterations in BA disposition if species differences are taken into account. -- Highlights: ► Bile acids (BAs) were measured in rat and human sandwich-cultured hepatocytes (SCH). ► Cell and medium BA concentrations

  7. Age-dependent changes in diastolic Ca2+ and Na+ concentrations in dystrophic cardiomyopathy: Role of Ca2+ entry and IP3

    International Nuclear Information System (INIS)

    Mijares, Alfredo; Altamirano, Francisco; Kolster, Juan; Adams, José A.; López, José R.

    2014-01-01

    Highlights: • Age-dependent increase in [Ca 2+ ] d and [Na + ] d in mdx cardiomyocytes. • Gadolinium significantly reduced both [Ca 2+ ] d and [Na + ] d at all ages. • IP 3 -pathway inhibition reduced cations concentrations in dystrophic cardiomyocytes. - Abstract: Duchenne muscular dystrophy (DMD) is a lethal X-inherited disease caused by dystrophin deficiency. Besides the relatively well characterized skeletal muscle degenerative processes, DMD is also associated with a dilated cardiomyopathy that leads to progressive heart failure at the end of the second decade. The aim of the present study was to characterize the diastolic Ca 2+ concentration ([Ca 2+ ] d ) and diastolic Na + concentration ([Na + ] d ) abnormalities in cardiomyocytes isolated from 3-, 6-, 9-, and 12-month old mdx mice using ion-selective microelectrodes. In addition, the contributions of gadolinium (Gd 3+ )-sensitive Ca 2+ entry and inositol triphosphate (IP 3 ) signaling pathways in abnormal [Ca 2+ ] d and [Na + ] d were investigated. Our results showed an age-dependent increase in both [Ca 2+ ] d and [Na + ] d in dystrophic cardiomyocytes compared to those isolated from age-matched wt mice. Gd 3+ treatment significantly reduced both [Ca 2+ ] d and [Na + ] d at all ages. In addition, blockade of the IP 3 -pathway with either U-73122 or xestospongin C significantly reduced ion concentrations in dystrophic cardiomyocytes. Co-treatment with U-73122 and Gd 3+ normalized both [Ca 2+ ] d and [Na + ] d at all ages in dystrophic cardiomyocytes. These data showed that loss of dystrophin in mdx cardiomyocytes produced an age-dependent intracellular Ca 2+ and Na + overload mediated at least in part by enhanced Ca 2+ entry through Gd 3+ sensitive transient receptor potential channels (TRPC), and by IP 3 receptors

  8. LncRNA Taurine-Upregulated Gene 1 Promotes Cell Proliferation by Inhibiting MicroRNA-9 in MCF-7 Cells.

    Science.gov (United States)

    Zhao, Xiao-Bo; Ren, Guo-Sheng

    2016-12-01

    This study was designed to investigate the role of taurine-upregulated gene 1 ( TUG1 ) in MCF-7 breast cancer cells and the molecular mechanism involved in the regulation of microRNA-9 (miR-9). The expression of TUG1 in breast cancer tissues and cells was evaluated using quantitative reverse transcription polymerase chain reaction. Cell viability was examined using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay; cell cycle progression and apoptosis were analyzed using flow cytometry. A dual luciferase reporter assay was used to detect the relationship between TUG1 and miR-9. The expression of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) was measured by western blot. Higher expression of TUG1 was observed in breast cancer tissues and cell lines than in the corresponding controls. TUG1 knockdown reduced proliferation, suppressed cell cycle progression, and promoted apoptosis of MCF-7 cells. The dual luciferase reporter assay showed that TUG1 could negatively regulate the expression of miR-9. MiR-9 inhibition abrogated the effect of TUG1 knockdown on the proliferation, cell cycle progression, and apoptosis of MCF-7 cells. TUG1 positively regulated the expression of MTHFD2 in breast cancer cells. TUG1 knockdown was significantly associated with decreased cell proliferation and it promoted apoptosis of breast cancer cells through the regulation of miR-9.

  9. Exposure to Tobacco Advertising and Promotion among School Children Aged 13-15 in Vietnam - an Overview from GYTS 2014.

    Science.gov (United States)

    Long, Tran Khanh; Son, Phung Xuan; Giang, Kim Bao; Hai, Phan Thi; Huyen, Doan Thi Thu; Khue, Luong Ngoc; Nga, Pham Thi Quynh; Lam, Nguyen Tuan; Minh, Hoang Van; Huong, Le Thi Thanh

    2016-01-01

    Evidence shows that tobacco advertising and promotion activities may increase tobacco consumption and usage, especially in youth. Despite the regulation on prohibiting advertisement of any tobacco product, tobacco advertisement and promotion activities are still common in Vietnam. This article presents current exposure to tobacco advertising and promotion (TAP) among school children aged 13 to 15 years in Vietnam in 2014 and potential influencing factors. Data from the Global Youth Tobacco Survey 2014 in Vietnam covering 3,430 school aged children were used. Both descriptive and analytical statistics were carried out with Stata 13 statistical software. Binary logistic regression was applied to explain the exposure to TAP among youth and examine relationships with individual factors. A significance level of padvertising or promotion. Wearing or otherwise using products related to tobacco was the most exposure TAP type reported by students (22.3%). The internet (22.1), points of sales (19.2) and social events (11.5) were three places that students aged 13-15 frequently were exposed to TAP. Binary logistic results showed that gender (female vs male) (OR = 0.61, 95%CI: 0.52 - 0.71), susceptibility to smoking (OR = 2.12, 95%CI: 1.53 - 2.92), closest friends' smoked (OR = 1.43, 95%CI: 1.2 - 1.7) and parents smoking status (OR = 2.83, 95%CI: 1.6 - 5.01) were significantly associated with TAP exposure among school-aged children. The research findings should contribute to effective implementation of measures for preventing and controlling tobacco use among students aged 13-15 in Viet Nam.

  10. Psychopathic personality development from ages 9 to 18: Genes and environment.

    Science.gov (United States)

    Tuvblad, Catherine; Wang, Pan; Bezdjian, Serena; Raine, Adrian; Baker, Laura A

    2016-02-01

    The genetic and environmental etiology of individual differences was examined in initial level and change in psychopathic personality from ages 9 to 18 years. A piecewise growth curve model, in which the first change score (G1) influenced all ages (9-10, 11-13, 14-15, and 16-18 years) and the second change score (G2) only influenced ages 14-15 and 16-18 years, fit the data better did than the standard single slope model, suggesting a turning point from childhood to adolescence. The results indicated that variations in levels and both change scores were mainly due to genetic (A) and nonshared environmental (E) influences (i.e., AE structure for G0, G1, and G2). No sex differences were found except on the mean values of level and change scores. Based on caregiver ratings, about 81% of variance in G0, 89% of variance in G1, and 94% of variance in G2 were explained by genetic factors, whereas for youth self-reports, these three proportions were 94%, 71%, and 66%, respectively. The larger contribution of genetic variance and covariance in caregiver ratings than in youth self-reports may suggest that caregivers considered the changes in their children to be more similar as compared to how the children viewed themselves.

  11. Tritium aging effect of LaNi4.9Al0.1Dx on de-deuterating kinetics

    International Nuclear Information System (INIS)

    Xiong Yifu; Luo Deli; Li Rong

    2002-01-01

    Kinetics parameters are measured at different aging times of LaNi 4.9 Al 0.1 alloy. The influence of tritium aging on kinetic feature of LaNi 4.9 Al 0.1 alloy is assessed. The results show that reaction rate decreases with aging time, but tritium aging does not change de-deuterating reaction order. De-deuterating reaction orders a (with respect to deuterium pressure) and b (with respect to deuterium content) are 0.5 and 1, respectively. Activation energy (E) increases with aging time. After 1120 d, the reaction rate constant is decreased by two orders of magnitude, activation energy is increased by a factor of 0.3

  12. Interaktion mit Digitalen Rechtschreibhilfen: Ein Vergleich von Schülertexten. Neue Wege zur Förderung der Rechtschreibkompetenz in der Sekundarstufe I.

    OpenAIRE

    Berndt, Elin-Birgit

    2002-01-01

    Die explorative Studie zeigt beispielhaft die Reichweite der Interaktion mit digitalen Rechtschreibhilfen in der Sekundarstufe I auf. Die im Schreibprozeß am Computer verfügbaren digitalen Rechtschreibhilfen - ABC-Prüfung der Textverarbeitungssoftware, digitale Rechtschreibwörterbücher und Thesaurus - erweisen sich für Schüler, die Schwierigkeiten mit der Orthographie haben, als sehr nützlich. Es gelingt ihnen nach der Überarbeitung ihrer Texte am PC orthographisch erheblich fehlerfreiere Tex...

  13. Policy initiatives to promote healthy aging.

    Science.gov (United States)

    Infeld, Donna Lind; Whitelaw, Nancy

    2002-08-01

    involve improving housing, nutrition, transportation, and other arenas that play a role in the health of communities and cities. According to the IOM, the most successful interventions are aimed at families, neighborhoods and communities. Interventions are also most likely to be successful when legislative, media, and marketing efforts support them [50]. These broader policies may actually have the most potential impact in terms of developing sustainable lifestyle changes that reach all Americans, especially those with the greatest health needs. Within the aging population, those with greatest health needs include members of minority groups, recent immigrants, and the old-old. These groups are often overlooked when designing and implementing health promotion programs. It is important, however, to remember, for patients and for ourselves, you are never too old to benefit from prevention.

  14. Age-dependent external root resorption during tooth movement in rats

    NARCIS (Netherlands)

    Ren, Yijin; Maltha, Jaap C.; Liem, Robert S. B.; Stokroos, Ietse; Kuijpers-Jagtman, Anne Marie

    OBJECTIVE: To investigate the effect of age on root resorption and distribution along different parts of the root during prolonged light force application. MATERIAL AND METHODS: Orthodontic appliances were placed in two groups of 30 rats (one group 6 weeks old, the other 9-12 months old), with

  15. Age-dependent external root resorption during tooth movement in rats.

    NARCIS (Netherlands)

    Ren, Y.; Maltha, J.C.; Liem, R.S.; Stokroos, I.; Kuijpers-Jagtman, A.M.

    2008-01-01

    OBJECTIVE: To investigate the effect of age on root resorption and distribution along different parts of the root during prolonged light force application. MATERIAL AND METHODS: Orthodontic appliances were placed in two groups of 30 rats (one group 6 weeks old, the other 9-12 months old), with

  16. Gender and Age Differences in Levels, Types and Locations of Physical Activity among Older Adults Living in Car-Dependent Neighborhoods.

    Science.gov (United States)

    Li, W; Procter-Gray, E; Churchill, L; Crouter, S E; Kane, K; Tian, J; Franklin, P D; Ockene, J K; Gurwitz, J

    2017-01-01

    A thorough understanding of gender differences in physical activity is critical to effective promotion of active living in older adults. To examine gender and age differences in levels, types and locations of physical activity. Cross-sectional observation. Car-dependent urban and rural neighborhoods in Worcester County, Massachusetts, USA. 111 men and 103 women aged 65 years and older. From 2012 to 2014, participants were queried on type, frequency and location of physical activity. Participants wore an accelerometer for 7 consecutive days. Compared to women, men had a higher mean daily step count (mean (SD) 4385 (2122) men vs. 3671(1723) women, p=0.008). Men reported higher frequencies of any physical activity and moderate-to-vigorous physical activity, and a lower frequency of physical activity inside the home. Mean daily step counts and frequency of physical activity outside the home decreased progressively with age for both men and women. Women had a sharper decline in frequencies of self-reported physical activity. Men had a significant decrease in utilitarian walking, which women did not (p=0.07). Among participants who reported participation in any physical activity (n=190), more women indicated exercising indoors more often (59% vs. 44%, p=0.04). The three most commonly cited locations for physical activity away from home for both genders were streets or sidewalks, shopping malls, and membership-only facilities (e.g., YMCA or YWCA). The most common types of physical activity, performed at least once in a typical month, with over 40% of both genders reporting, included light housework, brisk walking, leisurely walking, and stretching. Levels, types and location preferences of physical activity differed substantially by gender. Levels of physical activity decreased progressively with age, with greater decline among women. Consideration of these gender differences is necessary to improve the effectiveness of active living promotion programs among older adults.

  17. Chewing Maintains Hippocampus-Dependent Cognitive Function.

    Science.gov (United States)

    Chen, Huayue; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

    2015-01-01

    Mastication (chewing) is important not only for food intake, but also for preserving and promoting the general health. Recent studies have showed that mastication helps to maintain cognitive functions in the hippocampus, a central nervous system region vital for spatial memory and learning. The purpose of this paper is to review the recent progress of the association between mastication and the hippocampus-dependent cognitive function. There are multiple neural circuits connecting the masticatory organs and the hippocampus. Both animal and human studies indicated that cognitive functioning is influenced by mastication. Masticatory dysfunction is associated with the hippocampal morphological impairments and the hippocampus-dependent spatial memory deficits, especially in elderly. Mastication is an effective behavior for maintaining the hippocampus-dependent cognitive performance, which deteriorates with aging. Therefore, chewing may represent a useful approach in preserving and promoting the hippocampus-dependent cognitive function in older people. We also discussed several possible mechanisms involved in the interaction between mastication and the hippocampal neurogenesis and the future directions for this unique fascinating research.

  18. O conceito sócio-filosófico de Alfredo Schütz e suas implicações epistemológicas para o campo da Comunicação

    Directory of Open Access Journals (Sweden)

    Ulrike Schröder

    2006-12-01

    Full Text Available No seu conceito de uma sociologia interpretativa, o sociólogo Alfred Schütz procura realizar uma análise profunda do nosso "mundo da vida" (s, partindo da convicção de que este mundo de sentido não representa uma realidade objetiva, mas sim, uma realidade interpretada e válida intersubjetivamente. Por isso, também não vivemos simplesmente em um uni-verso fixo, mas sim, em multi-versos, cada um marcado por um outro estilo epistemológico. O artigo apresenta as características essenciais da teoria de Schütz, focalizando a atualidade do seu conceito, que indica possibilidades de tornar este fundamento teórico base para estudos empíricos no campo da comunicação hoje em dia.

  19. Healthy brain ageing assessed with 18F-FDG PET and age-dependent recovery factors after partial volume effect correction

    Energy Technology Data Exchange (ETDEWEB)

    Bonte, Stijn [IBiTech, Ghent, (Belgium); Ghent University, iMinds - Medical Image and Signal Processing (MEDISIP), Department of Electronics and Information Systems, Ghent (Belgium); University Hospital, Department of Radiology and Nuclear Medicine, Ghent (Belgium); Vandemaele, Pieter; Deblaere, Karel; Goethals, Ingeborg [University Hospital, Department of Radiology and Nuclear Medicine, Ghent (Belgium); Verleden, Stijn; Audenaert, Kurt [University Hospital, Department of Psychiatry, Ghent (Belgium); Holen, Roel van [Ghent University, iMinds - Medical Image and Signal Processing (MEDISIP), Department of Electronics and Information Systems, Ghent (Belgium)

    2017-05-15

    The mechanisms of ageing of the healthy brain are not entirely clarified to date. In recent years several authors have tried to elucidate this topic by using {sup 18}F-FDG positron emission tomography. However, when correcting for partial volume effects (PVE), divergent results were reported. Therefore, it is necessary to evaluate these methods in the presence of atrophy due to ageing. In this paper we first evaluate the performance of two PVE correction techniques with a phantom study: the Rousset method and iterative deconvolution. We show that the ability of the latter method to recover the true activity in a small region decreases with increasing age due to brain atrophy. Next, we have calculated age-dependent recovery factors to correct for this incomplete recovery. These factors were applied to PVE-corrected {sup 18}F-FDG PET scans of healthy subjects for mapping the agedependent metabolism in the brain. Many regions in the brain show a reduced metabolism with ageing, especially in grey matter in the frontal and temporal lobe. An increased metabolism is found in grey matter of the cerebellum and thalamus. Our study resulted in age-dependent recovery factors which can be applied following standard PVE correction methods. Cancelling the effect of atrophy, we found regional changes in {sup 18}F-FDG metabolism with ageing. A decreasing trend is found in the frontal and temporal lobe, whereas an increasing metabolism with ageing is observed in the thalamus and cerebellum.

  20. Senescence of the adaptive immune system in health and aging-associated autoimmune disease

    NARCIS (Netherlands)

    van der Geest, Kornelis Stephan Mario

    2015-01-01

    Aging of the immune system may contribute to the development of aging-associated autoimmune diseases, such as giant cell arteritis, polymyalgia rheumatica and rheumatoid arthritis. The aim of this thesis was to identify aging-dependent changes of the adaptive immune system that promote autoimmunity

  1. Myxoma virus protein M029 is a dual function immunomodulator that inhibits PKR and also conscripts RHA/DHX9 to promote expanded host tropism and viral replication.

    Directory of Open Access Journals (Sweden)

    Masmudur M Rahman

    Full Text Available Myxoma virus (MYXV-encoded protein M029 is a member of the poxvirus E3 family of dsRNA-binding proteins that antagonize the cellular interferon signaling pathways. In order to investigate additional functions of M029, we have constructed a series of targeted M029-minus (vMyx-M029KO and vMyx-M029ID and V5-tagged M029 MYXV. We found that M029 plays a pivotal role in determining the cellular tropism of MYXV in all mammalian cells tested. The M029-minus viruses were able to replicate only in engineered cell lines that stably express a complementing protein, such as vaccinia E3, but underwent abortive or abated infection in all other tested mammalian cell lines. The M029-minus viruses were dramatically attenuated in susceptible host European rabbits and caused no observable signs of myxomatosis. Using V5-tagged M029 virus, we observed that M029 expressed as an early viral protein is localized in both the nuclear and cytosolic compartments in virus-infected cells, and is also incorporated into virions. Using proteomic approaches, we have identified Protein Kinase R (PKR and RNA helicase A (RHA/DHX9 as two cellular binding partners of M029 protein. In virus-infected cells, M029 interacts with PKR in a dsRNA-dependent manner, while binding with DHX9 was not dependent on dsRNA. Significantly, PKR knockdown in human cells rescued the replication defect of the M029-knockout viruses. Unexpectedly, this rescue of M029-minus virus replication by PKR depletion could then be reversed by RHA/DHX9 knockdown in human monocytic THP1 cells. This indicates that M029 not only inhibits generic PKR anti-viral pathways, but also binds and conscripts RHA/DHX9 as a pro-viral effector to promote virus replication in THP1 cells. Thus, M029 is a critical host range and virulence factor for MYXV that is required for replication in all mammalian cells by antagonizing PKR-mediated anti-viral functions, and also conscripts pro-viral RHA/DHX9 to promote viral replication

  2. Myxoma Virus Protein M029 Is a Dual Function Immunomodulator that Inhibits PKR and Also Conscripts RHA/DHX9 to Promote Expanded Host Tropism and Viral Replication

    Science.gov (United States)

    Rahman, Masmudur M.; Liu, Jia; Chan, Winnie M.; Rothenburg, Stefan; McFadden, Grant

    2013-01-01

    Myxoma virus (MYXV)-encoded protein M029 is a member of the poxvirus E3 family of dsRNA-binding proteins that antagonize the cellular interferon signaling pathways. In order to investigate additional functions of M029, we have constructed a series of targeted M029-minus (vMyx-M029KO and vMyx-M029ID) and V5-tagged M029 MYXV. We found that M029 plays a pivotal role in determining the cellular tropism of MYXV in all mammalian cells tested. The M029-minus viruses were able to replicate only in engineered cell lines that stably express a complementing protein, such as vaccinia E3, but underwent abortive or abated infection in all other tested mammalian cell lines. The M029-minus viruses were dramatically attenuated in susceptible host European rabbits and caused no observable signs of myxomatosis. Using V5-tagged M029 virus, we observed that M029 expressed as an early viral protein is localized in both the nuclear and cytosolic compartments in virus-infected cells, and is also incorporated into virions. Using proteomic approaches, we have identified Protein Kinase R (PKR) and RNA helicase A (RHA)/DHX9 as two cellular binding partners of M029 protein. In virus-infected cells, M029 interacts with PKR in a dsRNA-dependent manner, while binding with DHX9 was not dependent on dsRNA. Significantly, PKR knockdown in human cells rescued the replication defect of the M029-knockout viruses. Unexpectedly, this rescue of M029-minus virus replication by PKR depletion could then be reversed by RHA/DHX9 knockdown in human monocytic THP1 cells. This indicates that M029 not only inhibits generic PKR anti-viral pathways, but also binds and conscripts RHA/DHX9 as a pro-viral effector to promote virus replication in THP1 cells. Thus, M029 is a critical host range and virulence factor for MYXV that is required for replication in all mammalian cells by antagonizing PKR-mediated anti-viral functions, and also conscripts pro-viral RHA/DHX9 to promote viral replication specifically in myeloid

  3. Population Consequences of Age-Dependent Maternal Effects in Rockfish (Sebastes spp.)

    OpenAIRE

    Lucero, Yasmin

    2007-01-01

    I present a model of the early life history of a rockfish that includes an age-dependent maternal effect. The model is designed to accurately reflect the diverse uncertainties we have about early life history processes. The first portion of this thesis is devoted to an analytical treatment of the deterministic early life history model. I emphasize uncertainty about the functional form of density-dependent processes in the juvenile stage. The remainder of the thesis is devoted to demonstrating...

  4. Genetic Association of the Porcine C9 Complement Component with Hemolytic Complement Activity

    Directory of Open Access Journals (Sweden)

    D. V. A. Khoa

    2015-09-01

    Full Text Available The complement system is a part of the natural immune regulation mechanism against invading pathogens. Complement activation from three different pathways (classical, lectin, and alternative leads to the formation of C5-convertase, an enzyme for cleavage of C5 into C5a and C5b, followed by C6, C7, C8, and C9 in membrane attack complex. The C9 is the last complement component of the terminal lytic pathway, which plays an important role in lysis of the target cells depending on its self-polymerization to form transmembrane channels. To address the association of C9 with traits related to disease resistance, the complete porcine C9 cDNA was comparatively sequenced to detect single nucleotide polymorphisms (SNPs in pigs of the breeds Hampshire (HS, Duroc (DU, Berlin miniature pig (BMP, German Landrace (LR, Pietrain (PIE, and Muong Khuong (Vietnamese potbelly pig. Genotyping was performed in 417 F2 animals of a resource population (DUMI: DU×BMP that were vaccinated with Mycoplasma hyopneumoniae, Aujeszky diseases virus and porcine respiratory and reproductive syndrome virus at 6, 14 and 16 weeks of age, respectively. Two SNPs were detected within the third exon. One of them has an amino acid substitution. The European porcine breeds (LR and PIE show higher allele frequency of these SNPs than Vietnamese porcine breed (MK. Association of the substitution SNP with hemolytic complement activity indicated statistically significant differences between genotypes in the classical pathway but not in the alternative pathway. The interactions between eight time points of measurement of complement activity before and after vaccinations and genotypes were significantly different. The difference in hemolytic complement activity in the both pathways depends on genotype, kind of vaccine, age and the interaction to the other complement components. These results promote the porcine C9 (pC9 as a candidate gene to improve general animal health in the future.

  5. Tritium aging effect on thermodynamic functions of LaNi4.9Al0.1

    International Nuclear Information System (INIS)

    Xiong Yifu; Li Rong; Luo Deli

    2001-01-01

    The influence of tritium aging on thermodynamic function of LaNi 4.9 Al 0.1 is measured. The results show that plateau pressures and reversible hydrogen capacity decrease with aging time, thermodynamics parameters such as ΔH, ΔS and plateau slopes of the P-T curve increase with aging time, tritium heel formed after 1120 d tritium exposure

  6. Peak oxygen uptake in swimmers and pupils

    Directory of Open Access Journals (Sweden)

    Emilson Colantonio

    2008-01-01

    The objectives of this study were: a to analyze the behavior of VO2MAX (absolute and relative of males of different age groups sex; b to compare VO2MAX (absolute and relative, of swimmers (SWM and schoolchildren (SCH in the same age groups. Seventy-one boys aged 7-17 years were evaluated (35 SWM and 36 SCH and distributed into the age groups 7-10, 11-14 and 15-17 years. Anthropometric measurements were taken (height, body mass and sum of skin folds and the metabolic (VO2MAX tests were carried out using VO2000® gas analysis and an Inbrasport ATL® treadmill, using a modified version of the Bruce protocol. Statistical analysis: ANOVA for repeated measures, followed by Tukey’s post hoc test (p<0.05. Absolute VO2MAX: there were statistically significant differences between all age groups and between SWM (0.99 + 0.20 and 1.27 + 0.21 L.min-1 and SCH (0.98 + 0.36 and 0.80 + 0.12 L.min-1. Relative VO2MAX: there were statistically significant differences between SWM1 and SWM2 (10.88 + 0.09 and 0.75 + 0.47 ml.kg-1.min-1 and between SCH1 and SCH3 (6.96 + 1.23 and 0.98 + 2.29 ml.kg-1.min-1, although SWM and SCH were different. The results indicate that VO2MAX increased as the subjects got older, which is the result of natural development. However, the effect of swimming training predominated. Although the behavior of the variable was similar for the 11-14 and 15-17 age groups, the figures for SWM and SCH are different at these ages, with the swimmers having higher VO2MAX.

  7. Involvement Of BDNF In Age-Dependent Alterations In The Hippocampus

    Directory of Open Access Journals (Sweden)

    Oliver Von Bohlen Und Halbach

    2010-08-01

    Full Text Available It is known since a long time that the hippocampus is sensitive to aging. Thus, there is a reduction in the hippocampal volume during aging. This age-related volume reduction is paralleled by behavioral and functional deficits in hippocampus-dependent learning and memory tasks. This age-related volume reduction of the hippocampus is not a consequence of an age-related loss of hippocampal neurons. The morphological changes associated with aging include reductions in the branching pattern of dendrites, as well as reductions in spine-densities, reductions in the densities of fibers projecting into the hippocampus as well as declines in the rate of neurogenesis. It is very unlikely that a single factor or a single class of molecules is responsible for all these age-related morphological changes in the hippocampus. Nevertheless, it would be of advantage to identify possible neuromodulators or neuropeptides that may contribute to these age-related changes. In this context, growth factors may play an important role in the maintenance of the postnatal hippocampal architecture. In this review it is hypothesized that brain-derived neurotrophic factor (BDNF is a factor critically involved in the regulation of age-related processes in the hippocampus. Moreover, evidences suggest that disturbances in the BDNF-system also affect hippocampal dysfunctions, as e.g. seen in major depression or in Alzheimer disease.

  8. Mise en pratique du schéma 2BSvs dans le groupe industriel Sofiprotéol : étude de cas sur toute la filière (de l’agriculteur au pétrolier

    Directory of Open Access Journals (Sweden)

    Guizouarn Kristell

    2015-01-01

    Full Text Available Pour réduire sensiblement les émissions de CO liées aux transports routiers, l’Union européenne mise sur le développement des biocarburants, en respectant des conditions de durabilité. Afin de répondre à cette obligation et d’être en mesure de démontrer la conformité du biodiesel à ces critères, depuis l’agriculteur jusqu’au distributeur pétrolier, la filière des oléagineux a engagé la rédaction d’un schéma de vérification volontaire : 2BSvs, pour Biomasse Biocarburant Schéma volontaire sur la durabilité. Reconnu par la Commission Européenne le 19 juillet 2011, le schéma 2BSvs couvre l’ensemble de la chaîne de production des biocarburants, du producteur de biomasse à l’entrée dans un entrepôt sous douanes. À travers une étude de cas sur toute la filière, de l’agriculteur au pétrolier, cet article présente les implications pour les acteurs de la filière oléagineuse, les changements intervenus depuis avril 2013, et les défis futurs à relever.

  9. Glucocorticoids facilitate the transcription from the human cytomegalovirus major immediate early promoter in glucocorticoid receptor- and nuclear factor-I-like protein-dependent manner

    International Nuclear Information System (INIS)

    Inoue-Toyoda, Maki; Kato, Kohsuke; Nagata, Kyosuke; Yoshikawa, Hiroyuki

    2015-01-01

    Human cytomegalovirus (HCMV) is a common and usually asymptomatic virus agent in healthy individuals. Initiation of HCMV productive infection depends on expression of the major immediate early (MIE) genes. The transcription of HCMV MIE genes is regulated by a diverse set of transcription factors. It was previously reported that productive HCMV infection is triggered probably by elevation of the plasma hydroxycorticoid level. However, it is poorly understood whether the transcription of MIE genes is directly regulated by glucocorticoid. Here, we found that the dexamethasone (DEX), a synthetic glucocorticoid, facilitates the transcription of HCMV MIE genes through the MIE promoter and enhancer in a glucocorticoid receptor (GR)-dependent manner. By competitive EMSA and reporter assays, we revealed that an NF-I like protein is involved in DEX-mediated transcriptional activation of the MIE promoter. Thus, this study supports a notion that the increased level of hydroxycorticoid in the third trimester of pregnancy reactivates HCMV virus production from the latent state. - Highlights: • DEX facilitates the transcription from the HCMV MIE promoter. • GR is involved in DEX-dependent transcription from the HCMV MIE promoter. • A 17 bp repeat is responsible for the HCMV MIE promoter activation by DEX. • An NF-I-like protein is involved in the HCMV MIE promoter activation by DEX

  10. Evolutionarily Conserved, Growth Plate Zone-Specific Regulation of the Matrilin-1 Promoter: L-Sox5/Sox6 and Nfi Factors Bound near TATA Finely Tune Activation by Sox9

    Science.gov (United States)

    Nagy, Andrea; Kénesi, Erzsébet; Rentsendorj, Otgonchimeg; Molnár, Annamária; Szénási, Tibor; Sinkó, Ildikó; Zvara, Ágnes; Thottathil Oommen, Sajit; Barta, Endre; Puskás, László G.; Lefebvre, Veronique; Kiss, Ibolya

    2011-01-01

    To help uncover the mechanisms underlying the staggered expression of cartilage-specific genes in the growth plate, we dissected the transcriptional mechanisms driving expression of the matrilin-1 gene (Matn1). We show that a unique assembly of evolutionarily conserved cis-acting elements in the Matn1 proximal promoter restricts expression to the proliferative and prehypertrophic zones of the growth plate. These elements functionally interact with distal elements and likewise are capable of restricting the domain of activity of a pancartilaginous Col2a1 enhancer. The proximal elements include a Pe1 element binding the chondrogenic L-Sox5, Sox6, and Sox9 proteins, a SI element binding Nfi proteins, and an initiator Ine element binding the Sox trio and other factors. Sox9 binding to Pe1 is indispensable for functional interaction with the distal promoter. Binding of L-Sox5/Sox6 to Ine and Nfib to SI modulates Sox9 transactivation in a protein dose-dependent manner, possibly to enhance Sox9 activity in early stages of chondrogenesis and repress it at later stages. Hence, our data suggest a novel model whereby Sox and Nfi proteins bind to conserved Matn1 proximal elements and functionally interact with each other to finely tune gene expression in specific zones of the cartilage growth plate. PMID:21173167

  11. Pharmacologic ATM but not ATR kinase inhibition abrogates p21-dependent G1 arrest and promotes gastrointestinal syndrome after total body irradiation.

    Science.gov (United States)

    Vendetti, Frank P; Leibowitz, Brian J; Barnes, Jennifer; Schamus, Sandy; Kiesel, Brian F; Abberbock, Shira; Conrads, Thomas; Clump, David Andy; Cadogan, Elaine; O'Connor, Mark J; Yu, Jian; Beumer, Jan H; Bakkenist, Christopher J

    2017-02-01

    We show that ATM kinase inhibition using AZ31 prior to 9 or 9.25 Gy total body irradiation (TBI) reduced median time to moribund in mice to 8 days. ATR kinase inhibition using AZD6738 prior to TBI did not reduce median time to moribund. The striking finding associated with ATM inhibition prior to TBI was increased crypt loss within the intestine epithelium. ATM inhibition reduced upregulation of p21, an inhibitor of cyclin-dependent kinases, and blocked G1 arrest after TBI thereby increasing the number of S phase cells in crypts in wild-type but not Cdkn1a(p21 CIP/WAF1 )-/- mice. In contrast, ATR inhibition increased upregulation of p21 after TBI. Thus, ATM activity is essential for p21-dependent arrest while ATR inhibition may potentiate arrest in crypt cells after TBI. Nevertheless, ATM inhibition reduced median time to moribund in Cdkn1a(p21 CIP/WAF1 )-/- mice after TBI. ATM inhibition also increased cell death in crypts at 4 h in Cdkn1a(p21 CIP/WAF1 )-/-, earlier than at 24 h in wild-type mice after TBI. In contrast, ATR inhibition decreased cell death in crypts in Cdkn1a(p21 CIP/WAF1 )-/- mice at 4 h after TBI. We conclude that ATM activity is essential for p21-dependent and p21-independent mechanisms that radioprotect intestinal crypts and that ATM inhibition promotes GI syndrome after TBI.

  12. Schisandrin B protects against solar irradiation-induced oxidative injury in BJ human fibroblasts.

    Science.gov (United States)

    Chiu, Po Yee; Lam, Philip Y; Yan, Chung Wai; Ko, Kam Ming

    2011-06-01

    The effects of schisandrin B (Sch B) and its analogs on solar irradiation-induced oxidative injury were examined in BJ human fibroblasts. Sch B and schisandrin C (Sch C) increased cellular reduced glutathione (GSH) level and protected against solar irradiation-induced oxidative injury. The photoprotection was paralleled by decreases in the elastases-type protease activity and matrix-metalloproteinases-1 expression in solar-irradiated fibroblasts. The cytochrome P-450-mediated metabolism of Sch B or Sch C caused ROS production. The results suggest that by virtue of its pro-oxidant action and the subsequent glutathione antioxidant response, Sch B or Sch C may offer the prospect of preventing skin photo-aging. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Early age-dependent impairments of context-dependent extinction learning, object recognition, and object-place learning occur in rats.

    Science.gov (United States)

    Wiescholleck, Valentina; Emma André, Marion Agnès; Manahan-Vaughan, Denise

    2014-03-01

    The hippocampus is vulnerable to age-dependent memory decline. Multiple forms of memory depend on adequate hippocampal function. Extinction learning comprises active inhibition of no longer relevant learned information concurrent with suppression of a previously learned reaction. It is highly dependent on context, and evidence exists that it requires hippocampal activation. In this study, we addressed whether context-based extinction as well as hippocampus-dependent tasks, such as object recognition and object-place recognition, are equally affected by moderate aging. Young (7-8 week old) and older (7-8 month old) Wistar rats were used. For the extinction study, animals learned that a particular floor context indicated that they should turn into one specific arm (e.g., left) to receive a food reward. On the day after reaching the learning criterion of 80% correct choices, the floor context was changed, no reward was given and animals were expected to extinguish the learned response. Both, young and older rats managed this first extinction trial in the new context with older rats showing a faster extinction performance. One day later, animals were returned to the T-maze with the original floor context and renewal effects were assessed. In this case, only young but not older rats showed the expected renewal effect (lower extinction ratio as compared to the day before). To assess general memory abilities, animals were tested in the standard object recognition and object-place memory tasks. Evaluations were made at 5 min, 1 h and 7 day intervals. Object recognition memory was poor at short-term and intermediate time-points in older but not young rats. Object-place memory performance was unaffected at 5 min, but impaired at 1 h in older but not young rats. Both groups were impaired at 7 days. These findings support that not only aspects of general memory, but also context-dependent extinction learning, are affected by moderate aging. This may reflect less flexibility in

  14. Chemical dependency and adolescent self-esteem.

    Science.gov (United States)

    Wasson, D; Anderson, M A

    1995-08-01

    The purpose of this descriptive study is to determine whether self-esteem differs between chemically dependent adolescents and adolescents from the general high school population. The Self-Esteem Inventory (Coopersmith, 1987) was completed by 119 adolescents (31 inpatient, 31 aftercare, and 57 general high school students) aged 13 to 18. Findings suggest that inpatient, chemically dependent adolescents have lower self-esteem than the other two groups. For the chemically dependent adolescent, nursing case management with communication among and between health care providers, school professionals, and family may facilitate successful, long-term recovery. For adolescents at risk for development of chemical dependence, nursing health promotion behaviors, such as early assessment and implementation of self-esteem-building activities, may assist in prevention of chemical dependency.

  15. Interleukin-33 promoting Th1 lymphocyte differentiation dependents on IL-12.

    Science.gov (United States)

    Komai-Koma, Mousa; Wang, Eryi; Kurowska-Stolarska, Mariola; Li, Dong; McSharry, Charles; Xu, Damo

    2016-03-01

    The pro-Th2 cytokine IL-33 is now emerging as an important Th1 cytokine-IFN-γ inducer in murine CD4(+) T cells that is essential for protective cell-mediated immunity against viral infection in mice. However, whether IL-33 can promote human Th1 cell differentiation and how IL-33 polarizes Th1 cells is less understood. We assessed the ability of IL-33 to induce Th1 cell differentiation and IFN-γ production in vitro and in vivo. We report here that IL-33 alone had no ability in Th1 cell polarization. However it potentiated IL-12-mediated Th1 cell differentiation and IFN-γ production in TCR-stimulated murine and human CD4(+) T cells in vitro and in vivo. IL-33 promoted Th1 cell development via MyD88 and synergized with IL-12 to enhance St2 and IL-12R expression in CD4(+) T cells. These data therefore provide a novel mechanism for Th1 cell differentiation and optimal induction of a Type 1 response. Thus, IL-33 is capable of inducing IL-12-dependent Th1 cell differentiation in human and mouse CD4(+) T cells. Copyright © 2015 The Authors. Published by Elsevier GmbH.. All rights reserved.

  16. Age- and sex-dependent model for estimating radioiodine dose to a normal thyroid

    International Nuclear Information System (INIS)

    Killough, G.G.; Eckerman, K.F.

    1986-01-01

    This paper describes the derivation of an age- and sex-dependent model of radioiodine dosimetry in the thyroid and the application of the model to estimating the thyroid dose for each of 4215 patients who were exposed to 131 I in diagnostic and therapeutic procedures. In most cases, the available data consisted of the patient's age at the time of administration, the patient's sex, the quantity of activity administered, the clinically-determined uptake of radioiodine by the thyroid, and the time after administration at which the uptake was determined. The metabolic model is of the form A(t) = K[exp(-μ 1 t) -exp(-μ 2 t)] (μCi), where μ 1 = λ/sub r/ - λ/sub i//sup b/ (i = 1, 2), λ/sub r/ is the radiological decay-rate coefficient, and λ/sub i//sup b/ are biological removal rate coefficients. The values of λ/sub i//sup b/ are determined by solving a nonlinear equation that depends on assumptions about the time or maximum uptake an the eventual biological loss rate (through which age dependence enters). The value of K may then be calculated from knowledge of the uptakes at a particular time. The dosimetric S-factor (rad/μCi-day) is based on specific absorbed fractions for photons of energy ranging from 0.01 to 4.0 MeV for thyroid masses from 1.29 to 19.6 g; the functional form of the S-factor also involves the thyroid mass explicitly, through which the dependence on age and sex enters. An analysis of sensitivity of the model to uncertainties in the thyroid mass and the biological removal rate for several age groups is reported. 12 references, 5 figures, 5 tables

  17. Gender and Age-Dependent Etiology of Community-Acquired Urinary Tract Infections

    Directory of Open Access Journals (Sweden)

    Enrico Magliano

    2012-01-01

    Full Text Available Urinary tract infections (UTIs are among the most frequent community-acquired infections worldwide. Escherichia coli is the most common UTI pathogen although underlying host factors such as patients’ age and gender may influence prevalence of causative agents. In this study, 61 273 consecutive urine samples received over a 22-month period from outpatients clinics of an urban area of north Italy underwent microbiological culture with subsequent bacterial identification and antimicrobial susceptibility testing of positive samples. A total of 13 820 uropathogens were isolated and their prevalence analyzed according to patient’s gender and age group. Overall Escherichia coli accounted for 67.6% of all isolates, followed by Klebsiella pneumoniae (8.8%, Enterococcus faecalis (6.3%, Proteus mirabilis (5.2%, and Pseudomonas aeruginosa (2.5%. Data stratification according to both age and gender showed E. coli isolation rates to be lower in both males aged ≥60 years (52.2%, E. faecalis and P. aeruginosa being more prevalent in this group (11.6% and 7.8%, resp., as well as in those aged ≤14 years (51.3% in whom P. mirabilis prevalence was found to be as high as 21.2%. Streptococcus agalactiae overall prevalence was found to be 2.3% although it was shown to occur most frequently in women aged between 15 and 59 years (4.1%. Susceptibility of E. coli to oral antimicrobial agents was demonstrated to be as follows: fosfomycin (72.9%, trimethoprim/sulfamethoxazole (72.9%, ciprofloxacin (76.8%, ampicillin (48.0%, and amoxicillin/clavulanate (77.5%. In conclusion, both patients’ age and gender are significant factors in determining UTIs etiology; they can increase accuracy in defining the causative uropathogen as well as providing useful guidance to empiric treatment.

  18. Long-term high-level exercise promotes muscle reinnervation with age.

    Science.gov (United States)

    Mosole, Simone; Carraro, Ugo; Kern, Helmut; Loefler, Stefan; Fruhmann, Hannah; Vogelauer, Michael; Burggraf, Samantha; Mayr, Winfried; Krenn, Matthias; Paternostro-Sluga, Tatjana; Hamar, Dusan; Cvecka, Jan; Sedliak, Milan; Tirpakova, Veronika; Sarabon, Nejc; Musarò, Antonio; Sandri, Marco; Protasi, Feliciano; Nori, Alessandra; Pond, Amber; Zampieri, Sandra

    2014-04-01

    The histologic features of aging muscle suggest that denervation contributes to atrophy, that immobility accelerates the process, and that routine exercise may protect against loss of motor units and muscle tissue. Here, we compared muscle biopsies from sedentary and physically active seniors and found that seniors with a long history of high-level recreational activity up to the time of muscle biopsy had 1) lower loss of muscle strength versus young men (32% loss in physically active vs 51% loss in sedentary seniors); 2) fewer small angulated (denervated) myofibers; 3) a higher percentage of fiber-type groups (reinnervated muscle fibers) that were almost exclusive of the slow type; and 4) sparse normal-size muscle fibers coexpressing fast and slow myosin heavy chains, which is not compatible with exercise-driven muscle-type transformation. The biopsies from the old physically active seniors varied from sparse fiber-type groupings to almost fully transformed muscle, suggesting that coexpressing fibers appear to fill gaps. Altogether, the data show that long-term physical activity promotes reinnervation of muscle fibers and suggest that decades of high-level exercise allow the body to adapt to age-related denervation by saving otherwise lost muscle fibers through selective recruitment to slow motor units. These effects on size and structure of myofibers may delay functional decline in late aging.

  19. Radiogenic age and isotopic studies: report 9. Current research 1995-F

    International Nuclear Information System (INIS)

    1996-01-01

    'Radiogenic Age and Isotopic Studies' is an annual collection of research presentations containing U-Pb, Sm-Nd, Rb-Sr, and 40 Ar- 39 Ar data generated by the Geochronology Laboratory under the auspices of the Continental Geoscience Division, Geological Survey of Canada. Report 9 contains 5 papers from regions across Canada, followed by a compilation of 40 Ar- 39 Ar and K-Ar ages. Authors herein present data, relate results to field settings, and make brief interpretations. Readers are thus reminded that much of the research encompassed represents 'work-in-progress' and that more extensive publications may follow at a later date

  20. Diagnosis and Management of Subclinical Hypothyroidism in Elderly Adults: A Review of the Literature.

    Science.gov (United States)

    Hennessey, James V; Espaillat, Ramon

    2015-08-01

    The estimated prevalence of subclinical hypothyroidism (SCH) in the general population is 3% to 8%. As the average age of the population in the United States and other countries continues to increase, the overall prevalence of SCH may also be expected to increase. Although age-related changes in thyroid function are well described, normal thyroid-stimulating hormone (TSH) reference limits, derived for age-specific populations, are not routinely used to identify thyroid dysfunction in elderly adults. Therefore, currently accepted values for the upper limit of normal of TSH may be inappropriate for diagnosing SCH in individuals aged 65 and older, resulting in potential overestimation of the prevalence of SCH in this population. This review discusses the current evidence of the effects of SCH on cardiovascular health and neuropsychiatric function in older adults. Although the results of some studies are conflicting, the overall evidence suggests that the consequences of SCH may be different for elderly adults than for younger populations. Treatment of SCH in older individuals requires special consideration with regard to thyroid hormone replacement therapy and expected clinical outcomes. Although careful identification of individuals with persistent SCH who could benefit from levothyroxine treatment is necessary, current evidence suggests that individuals with TSH levels greater than 10 mIU/L who test positive for antithyroid antibodies or are symptomatic may benefit from levothyroxine treatment to reduce the risk of progression to overt hypothyroidism, decrease the risk of adverse cardiovascular events, and improve their quality of life. After treatment is initiated, careful monitoring is essential. © 2015, The Authors. The Journal of the American Geriatrics Society published by Wiley Periodicals, Inc. on behalf of The American Geriatrics Society.

  1. Effects of 18 months of L-T4 replacement in women with subclinical hypothyroidism.

    LENUS (Irish Health Repository)

    Adrees, M

    2012-02-01

    CONTEXT: Some of the cardiovascular and renal abnormalities seen in overt hypothyroidism have also been reported in subclinical hypothyroidism (SCH). Short-term L-T4 replacement in SCH improves cardiovascular risk markers and reduces carotid intima-media thickness (CIMT), a surrogate marker of atherosclerosis. The haemodynamic and renal effects of L-T4 replacement in SCH are poorly understood. OBJECTIVES: To compare cardiovascular risk factors and renal variables in women with SCH and normal women. To study the effects of L-T4 replacement in SCH subjects on these variables and on structural and functional changes in common carotid and brachial arteries. DESIGN: Fifty-six women with SCH before and after L-T4 replacement for 18 months and 56 normal women of similar age distribution were studied. Blood Pressure (BP), plasma lipids and homocysteine were measured and renal function evaluated [estimation of glomerular filtration rate (eGFR) using standard equations and measurement of serum Cystatin-C] in women with SCH before and after 18 months of l-T4, and in healthy women. CIMT and endothelial function (using brachial artery ultrasound) were studied before and after L-T4 in a subgroup of women with SCH. RESULTS: Systolic and diastolic BP, total cholesterol, triglyceride, LDL-cholesterol, lipoprotein(a) and homocysteine were greater in SCH (P < 0.05), and following L-T4 replacement decreased (P < 0.05) to levels that no longer differed from normal subjects. Estimated GFR was reduced and serum Cystatin-C increased (P < 0.05) in SCH. These variables also normalized following L-T4. Following L-T4 replacement the carotid artery baseline diameter increased by 7.1% and CIMT decreased by a mean value of 13%, while brachial artery diameter increased basally by 12.5% and following endothelium-dependent vasodilatation by 17.5% (P < 0.05). However, the increment following reactive hyperaemia did not differ before or following L-T4 replacement. CONCLUSION: Normalization of

  2. Reduced childhood mortality after standard measles vaccination at 4-8 months compared with 9-11 months of age

    DEFF Research Database (Denmark)

    Aaby, Peter; Andersen, M; Sodemann, Morten

    1993-01-01

    To evaluate the impact on mortality of standard Schwarz measles immunisation before 9 months of age.......To evaluate the impact on mortality of standard Schwarz measles immunisation before 9 months of age....

  3. Calculation of age-dependent effective doses for external exposure using the MCNP code

    International Nuclear Information System (INIS)

    Hung, Tran Van

    2013-01-01

    Age-dependent effective dose for external exposure to photons uniformly distributed in air were calculated. Firstly, organ doses were calculated with a series of age-specific MIRD-5 type phantoms using the Monte Carlo code MCNP. The calculations were performed for mono-energetic photon sources with source energies from 10 keV to 5 MeV and for phantoms of newborn, 1, 5, 10, and 15 years-old and adult. Then, the effective doses to the different age-phantoms from the mono-energetic photon sources were estimated based on the obtained organ doses. From the calculated results, it is shown that the effective doses depend on the body size; the effective doses in younger phantoms are higher than those in the older phantoms, especially below 100 keV. (orig.)

  4. Calculation of age-dependent effective doses for external exposure using the MCNP code

    Energy Technology Data Exchange (ETDEWEB)

    Hung, Tran Van [Research and Development Center for Radiation Technology, ThuDuc, HoChiMinh City (VT)

    2013-07-15

    Age-dependent effective dose for external exposure to photons uniformly distributed in air were calculated. Firstly, organ doses were calculated with a series of age-specific MIRD-5 type phantoms using the Monte Carlo code MCNP. The calculations were performed for mono-energetic photon sources with source energies from 10 keV to 5 MeV and for phantoms of newborn, 1, 5, 10, and 15 years-old and adult. Then, the effective doses to the different age-phantoms from the mono-energetic photon sources were estimated based on the obtained organ doses. From the calculated results, it is shown that the effective doses depend on the body size; the effective doses in younger phantoms are higher than those in the older phantoms, especially below 100 keV. (orig.)

  5. Les schémas de sélection ovins laitiers en France : utilisation et importance des techniques modernes de reproduction

    OpenAIRE

    Astruc, J.M.; Lagriffoul, G.; Belloc, J.P.; Briois, M.; Cachenaut, J.B.; Horent, M.H.; Teinturier, M.H.

    1995-01-01

    La mise en oeuvre de programmes de sélection laitière, à l’échelle de toute une population ovine, suppose de développer un travail de sélection entre éleveurs, fondé sur l’organisation et la valorisation de liens génétiques entre troupeaux, essentiellement grâce à l’utilisation de l’IA. La situation en France est à cet égard révélatrice des différents niveaux d’organisation des schémas de sélection.

  6. Intracellular Wnt/Beta-Catenin Signaling Underlying 17beta-Estradiol-Induced Matrix Metalloproteinase 9 Expression in Human Endometriosis.

    Science.gov (United States)

    Zhang, Ling; Xiong, Wenqian; Xiong, Yao; Liu, Hengwei; Li, Na; Du, Yu; Liu, Yi

    2016-03-01

    Extracellular matrix remodeling is necessary for ectopic endometrium implantation. Many studies have shown an increased expression of matrix metalloproteinase 9 (MMP9) in the ectopic endometrium of endometriosis. However, the signaling pathways and cellular effects related to this process remain incompletely elucidated. The objective of our study was to investigate the association between MMP9 and the Wnt signaling pathway under the regulation of 17beta-estradiol (E2) in endometrial stromal cells. We found that MMP9 was elevated in tissues from women with endometriosis compared with normal women. Furthermore, MMP9 and beta-catenin increased concurrently in a time- and dose-dependent manner after E2 treatment. To clarify the relationship between MMP9 and beta-catenin, we performed luciferase promoter reporter and chromatin immunoprecipitation assays. A beta-catenin/TCF3/LEF1 complex bound to a specific site on the MMP9 promoter that promoted MMP9 gene and protein expression. The promotion of MMP9 by the Wnt signaling pathway under the regulation of E2 may contribute to the pathophysiology of this disease. © 2016 by the Society for the Study of Reproduction, Inc.

  7. Proteasome Failure Promotes Positioning of Lysosomes around the Aggresome via Local Block of Microtubule-Dependent Transport

    Science.gov (United States)

    Zaarur, Nava; Meriin, Anatoli B.; Bejarano, Eloy; Xu, Xiaobin; Gabai, Vladimir L.; Cuervo, Ana Maria

    2014-01-01

    Ubiquitinated proteins aggregate upon proteasome failure, and the aggregates are transported to the aggresome. In aggresomes, protein aggregates are actively degraded by the autophagy-lysosome pathway, but why targeting the aggresome promotes degradation of aggregated species is currently unknown. Here we report that the important factor in this process is clustering of lysosomes around the aggresome via a novel mechanism. Proteasome inhibition causes formation of a zone around the centrosome where microtubular transport of lysosomes is suppressed, resulting in their entrapment and accumulation. Microtubule-dependent transport of other organelles, including autophagosomes, mitochondria, and endosomes, is also blocked in this entrapment zone (E-zone), while movement of organelles at the cell periphery remains unaffected. Following the whole-genome small interfering RNA (siRNA) screen for proteins involved in aggresome formation, we defined the pathway that regulates formation of the E-zone, including the Stk11 protein kinase, the Usp9x deubiquitinating enzyme, and their substrate kinase MARK4. Therefore, upon proteasome failure, targeting of aggregated proteins of the aggresome is coordinated with lysosome positioning around this body to facilitate degradation of the abnormal species. PMID:24469403

  8. Mathematical modelling the age dependence of Epstein-Barr virus associated infectious mononucleosis.

    Science.gov (United States)

    Huynh, Giao T; Adler, Frederick R

    2012-09-01

    Most people get Epstein-Barr virus (EBV) infection at young age and are asymptomatic. Primary EBV infection in adolescents and young adults, however, often leads to infectious mononucleosis (IM) with symptoms including fever, fatigue and sore throat that can persist for months. Expansion in the number of CD8(+) T cells, especially against EBV lytic proteins, are the main cause of these symptoms. We propose a mathematical model for the regulation of EBV infection within a host to address the dependence of IM on age. This model tracks the number of virus, infected B cell and epithelial cell and CD8(+) T-cell responses to the infection. We use this model to investigate three hypotheses for the high incidence of IM in teenagers and young adults: saliva and antibody effects that increase with age, high cross-reactive T-cell responses and a high initial viral load. The model supports the first two of these hypotheses and suggests that variation in host antibody responses and the complexity of the pre-existing cross-reactive T-cell repertoire, both of which depend on age, may play important roles in the etiology of IM.

  9. Does tinnitus distress depend on age of onset?

    Directory of Open Access Journals (Sweden)

    Winfried Schlee

    Full Text Available OBJECTIVES: Tinnitus is the perception of a sound in the absence of any physical source of it. About 5-15% of the population report hearing such a tinnitus and about 1-2% suffer from their tinnitus leading to anxiety, sleep disorders or depression. It is currently not completely understood why some people feel distressed by their tinnitus, while others don't. Several studies indicate that the amount of tinnitus distress is associated with many factors including comorbid anxiety, comorbid depression, personality, the psychosocial situation, the amount of the related hearing loss and the loudness of the tinnitus. Furthermore, theoretical considerations suggest an impact of the age at tinnitus onset influencing tinnitus distress. METHODS: Based on a sample of 755 normal hearing tinnitus patients we tested this assumption. All participants answered a questionnaire on the amount of tinnitus distress together with a large variety of clinical and demographic data. RESULTS: Patients with an earlier onset of tinnitus suffer significantly less than patients with an onset later in life. Furthermore, patients with a later onset of tinnitus describe their course of tinnitus distress as more abrupt and distressing right from the beginning. CONCLUSION: We argue that a decline of compensatory brain plasticity in older age accounts for this age-dependent tinnitus decompensation.

  10. Does tinnitus distress depend on age of onset?

    Science.gov (United States)

    Schlee, Winfried; Kleinjung, Tobias; Hiller, Wolfgang; Goebel, Gerhard; Kolassa, Iris-Tatjana; Langguth, Berthold

    2011-01-01

    Tinnitus is the perception of a sound in the absence of any physical source of it. About 5-15% of the population report hearing such a tinnitus and about 1-2% suffer from their tinnitus leading to anxiety, sleep disorders or depression. It is currently not completely understood why some people feel distressed by their tinnitus, while others don't. Several studies indicate that the amount of tinnitus distress is associated with many factors including comorbid anxiety, comorbid depression, personality, the psychosocial situation, the amount of the related hearing loss and the loudness of the tinnitus. Furthermore, theoretical considerations suggest an impact of the age at tinnitus onset influencing tinnitus distress. Based on a sample of 755 normal hearing tinnitus patients we tested this assumption. All participants answered a questionnaire on the amount of tinnitus distress together with a large variety of clinical and demographic data. Patients with an earlier onset of tinnitus suffer significantly less than patients with an onset later in life. Furthermore, patients with a later onset of tinnitus describe their course of tinnitus distress as more abrupt and distressing right from the beginning. We argue that a decline of compensatory brain plasticity in older age accounts for this age-dependent tinnitus decompensation.

  11. Does Tinnitus Distress Depend on Age of Onset?

    Science.gov (United States)

    Schlee, Winfried; Kleinjung, Tobias; Hiller, Wolfgang; Goebel, Gerhard; Kolassa, Iris-Tatjana; Langguth, Berthold

    2011-01-01

    Objectives Tinnitus is the perception of a sound in the absence of any physical source of it. About 5–15% of the population report hearing such a tinnitus and about 1–2% suffer from their tinnitus leading to anxiety, sleep disorders or depression. It is currently not completely understood why some people feel distressed by their tinnitus, while others don't. Several studies indicate that the amount of tinnitus distress is associated with many factors including comorbid anxiety, comorbid depression, personality, the psychosocial situation, the amount of the related hearing loss and the loudness of the tinnitus. Furthermore, theoretical considerations suggest an impact of the age at tinnitus onset influencing tinnitus distress. Methods Based on a sample of 755 normal hearing tinnitus patients we tested this assumption. All participants answered a questionnaire on the amount of tinnitus distress together with a large variety of clinical and demographic data. Results Patients with an earlier onset of tinnitus suffer significantly less than patients with an onset later in life. Furthermore, patients with a later onset of tinnitus describe their course of tinnitus distress as more abrupt and distressing right from the beginning. Conclusion We argue that a decline of compensatory brain plasticity in older age accounts for this age-dependent tinnitus decompensation. PMID:22125612

  12. Aging of microplastics promotes their ingestion by marine zooplankton.

    Science.gov (United States)

    Vroom, Renske J E; Koelmans, Albert A; Besseling, Ellen; Halsband, Claudia

    2017-12-01

    Microplastics (microplastics to test their impacts, while aging processes such as weathering and biofouling alter the characteristics of plastic particles in the marine environment. We investigated zooplankton ingestion of polystyrene beads (15 and 30 μm) and fragments (≤30 μm), and tested the hypothesis that microplastics previously exposed to marine conditions (aged) are ingested at higher rates than pristine microplastics. Polystyrene beads were aged by soaking in natural local seawater for three weeks. Three zooplankton taxa ingested microplastics, excluding the copepod Pseudocalanus spp., but the proportions of individuals ingesting plastic and the number of particles ingested were taxon and life stage specific and dependent on plastic size. All stages of Calanus finmarchicus ingested polystyrene fragments. Aged microbeads were preferred over pristine ones by females of Acartia longiremis as well as juvenile copepodites CV and adults of Calanus finmarchicus. The preference for aged microplastics may be attributed to the formation of a biofilm. Such a coating, made up of natural microbes, may contain similar prey as the copepods feed on in the water column and secrete chemical exudates that aid chemodetection and thus increase the attractiveness of the particles as food items. Much of the ingested plastic was, however, egested within a short time period (2-4 h) and the survival of adult Calanus females was not affected in an 11-day exposure. Negative effects of microplastics ingestion were thus limited. Our findings emphasize, however, that aging plays an important role in the transformation of microplastics at sea and ingestion by grazers, and should thus be considered in future microplastics ingestion studies and estimates of microplastics transfer into the marine food web. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Spain: promoting the welfare of older adults in the context of population aging.

    Science.gov (United States)

    Serrano, Juan P; Latorre, José M; Gatz, Margaret

    2014-10-01

    Spain is one of the European countries with the most significant societal changes in the 21st century contributing to an aging population, in particular, high life expectancy coupled with low fertility, which will result in a doubling of the old-age dependency ratio. Demographic aging implies important challenges that affect the lives of people, families, the economy, public finances, and the reorganization of the health and social systems. Currently, the older population has become particularly vulnerable due to the economic crisis taking place in Spain, which has brought about the need for new policies and systems to protect older persons. The pension system is under the greatest threat in conjunction with possible changes in the national health care system. This report presents a general view of the main factors that surround and affect older adults in Spain, as well as policies developed by the government in response to the current and future situation. We highlight demographic predictions for the coming decades, quality-of-life indicators, situations of dependency, active aging policies, and the main research programs related to gerontology in Spain. © Crown copyright 2014.

  14. Nutrients, Microglia Aging, and Brain Aging

    Directory of Open Access Journals (Sweden)

    Zhou Wu

    2016-01-01

    Full Text Available As the life expectancy continues to increase, the cognitive decline associated with Alzheimer’s disease (AD becomes a big major issue in the world. After cellular activation upon systemic inflammation, microglia, the resident immune cells in the brain, start to release proinflammatory mediators to trigger neuroinflammation. We have found that chronic systemic inflammatory challenges induce differential age-dependent microglial responses, which are in line with the impairment of learning and memory, even in middle-aged animals. We thus raise the concept of “microglia aging.” This concept is based on the fact that microglia are the key contributor to the acceleration of cognitive decline, which is the major sign of brain aging. On the other hand, inflammation induces oxidative stress and DNA damage, which leads to the overproduction of reactive oxygen species by the numerous types of cells, including macrophages and microglia. Oxidative stress-damaged cells successively produce larger amounts of inflammatory mediators to promote microglia aging. Nutrients are necessary for maintaining general health, including the health of brain. The intake of antioxidant nutrients reduces both systemic inflammation and neuroinflammation and thus reduces cognitive decline during aging. We herein review our microglia aging concept and discuss systemic inflammation and microglia aging. We propose that a nutritional approach to controlling microglia aging will open a new window for healthy brain aging.

  15. Nutrients, Microglia Aging, and Brain Aging.

    Science.gov (United States)

    Wu, Zhou; Yu, Janchun; Zhu, Aiqin; Nakanishi, Hiroshi

    2016-01-01

    As the life expectancy continues to increase, the cognitive decline associated with Alzheimer's disease (AD) becomes a big major issue in the world. After cellular activation upon systemic inflammation, microglia, the resident immune cells in the brain, start to release proinflammatory mediators to trigger neuroinflammation. We have found that chronic systemic inflammatory challenges induce differential age-dependent microglial responses, which are in line with the impairment of learning and memory, even in middle-aged animals. We thus raise the concept of "microglia aging." This concept is based on the fact that microglia are the key contributor to the acceleration of cognitive decline, which is the major sign of brain aging. On the other hand, inflammation induces oxidative stress and DNA damage, which leads to the overproduction of reactive oxygen species by the numerous types of cells, including macrophages and microglia. Oxidative stress-damaged cells successively produce larger amounts of inflammatory mediators to promote microglia aging. Nutrients are necessary for maintaining general health, including the health of brain. The intake of antioxidant nutrients reduces both systemic inflammation and neuroinflammation and thus reduces cognitive decline during aging. We herein review our microglia aging concept and discuss systemic inflammation and microglia aging. We propose that a nutritional approach to controlling microglia aging will open a new window for healthy brain aging.

  16. Age-dependent effective doses for radionuclides uniformly distributed in air

    International Nuclear Information System (INIS)

    Hung, Tran Van

    2014-01-01

    Age-dependent effective doses for external exposure to photons emitted by radionuclides uniformly distributed in air are reported. The calculations were performed for 160 radionuclides, which are important for safety assessment of nuclear facilities. The energies and intensities of photons emitted from radionuclides were taken from the decay data DECDC used for dose calculations. The results are tabulated in the form of effective dose per unit concentration and time (Sv per Bq s m -3 ) for 6 age groups: newborn, 1, 5, 10 and 15 years-old and adult. The effective doses for the adult are also compared to values given in the literature.

  17. Tat-dependent repression of human immunodeficiency virus type 1 long terminal repeat promoter activity by fusion of cellular transcription factors

    International Nuclear Information System (INIS)

    Zhao Cunyou; Chen Yali; Park, Jiyoung; Kim, Jae Bum; Tang Hong

    2004-01-01

    Transcription initiation from HIV-1 long terminal repeat (LTR) promoter requires the virally encoded transactivator, Tat, and several cellular co-factors to accomplish the Tat-dependent processive transcription elongation. Individual cellular transcription activators, LBP-1b and Oct-1, on the other hand, have been shown to inhibit LTR promoter activities probably via competitive binding against TFIID to the TATA-box in LTR promoter. To explore the genetic interference strategies against the viral replication, we took advantage of the existence of the bipartite DNA binding domains and the repression domains of LBP-1b and Oct-1 factors to generate a chimeric transcription repressor. Our results indicated that the fusion protein of LBP-1b and Oct-1 exhibited higher DNA binding affinity to the viral promoter than the individual factors, and little interference with the host cell gene expression due to its anticipated rare cognate DNA sites in the host cell genome. Moreover, the chimera exerted increased Tat-dependent repression of transcription initiation at the LTR promoter both in vitro and in vivo compared to LBP-1b, Oct-1 or combination of LBP-1b and Oct-1. These results might provide the lead in generating a therapeutic reagent useful to suppress HIV-1 replication

  18. Transcription Factor SOX5 Promotes the Migration and Invasion of Fibroblast-Like Synoviocytes in Part by Regulating MMP-9 Expression in Collagen-Induced Arthritis

    Directory of Open Access Journals (Sweden)

    Yumeng Shi

    2018-04-01

    Full Text Available ObjectivesFibroblast-like synoviocytes (FLS exhibit a unique aggressive phenotype in rheumatoid arthritis (RA. Increased FLS migration and subsequent invasion of the extracellular matrix are essential to joint destruction in RA. Our previous research reported that transcription factor SOX5 was highly expressed in RA-FLS. Here, the effects of SOX5 in RA-FLS migration and invasion will be investigated.MethodsThe migration and invasion of RA-FLS were evaluated using a transwell chamber assay. The expression of several potential SOX5-targeted genes, including matrix metalloproteinases (MMP-1, 2, 3 and 9, chemokines (CCL4, CCL2, CCR5 and CCR2, and pro-inflammatory cytokines (TNF-α and IL-6, were examined in RA-FLS using SOX5 gain- and loss-of-function study. The molecular mechanisms of SOX5-mediated MMP-9 expressions were assayed by luciferase reporter gene and chromatin immunoprecipitation (ChIP studies. The in vivo effect of SOX5 on FLS migration and invasion was examined using collagen-induced arthritis (CIA in DBA/1J mice.ResultsKnockdown SOX5 decreased lamellipodium formation, migration, and invasion of RA-FLS. The expression of MMP-9 was the only gene tested to be concomitantly affected by silencing or overexpressing SOX5. ChIP assay revealed that SOX5 was bound to the MMP-9 promoter in RA-FLS. The overexpression of SOX5 markedly enhanced the MMP-9 promoter activity, and specific deletion of a putative SOX5-binding site in MMP-9 promoter diminished this promoter-driven transcription in FLS. Locally knocked down SOX5 inhibited MMP-9 expression in the joint tissue and reduced pannus migration and invasion into the cartilage in CIA mice.ConclusionSOX5 plays a novel role in mediating migration and invasion of FLS in part by regulating MMP-9 expression in RA.

  19. Transcription Factor SOX5 Promotes the Migration and Invasion of Fibroblast-Like Synoviocytes in Part by Regulating MMP-9 Expression in Collagen-Induced Arthritis.

    Science.gov (United States)

    Shi, Yumeng; Wu, Qin; Xuan, Wenhua; Feng, Xiaoke; Wang, Fang; Tsao, Betty P; Zhang, Miaojia; Tan, Wenfeng

    2018-01-01

    Fibroblast-like synoviocytes (FLS) exhibit a unique aggressive phenotype in rheumatoid arthritis (RA). Increased FLS migration and subsequent invasion of the extracellular matrix are essential to joint destruction in RA. Our previous research reported that transcription factor SOX5 was highly expressed in RA-FLS. Here, the effects of SOX5 in RA-FLS migration and invasion will be investigated. The migration and invasion of RA-FLS were evaluated using a transwell chamber assay. The expression of several potential SOX5-targeted genes, including matrix metalloproteinases (MMP-1, 2, 3 and 9), chemokines (CCL4, CCL2, CCR5 and CCR2), and pro-inflammatory cytokines (TNF-α and IL-6), were examined in RA-FLS using SOX5 gain- and loss-of-function study. The molecular mechanisms of SOX5-mediated MMP-9 expressions were assayed by luciferase reporter gene and chromatin immunoprecipitation (ChIP) studies. The in vivo effect of SOX5 on FLS migration and invasion was examined using collagen-induced arthritis (CIA) in DBA/1J mice. Knockdown SOX5 decreased lamellipodium formation, migration, and invasion of RA-FLS. The expression of MMP-9 was the only gene tested to be concomitantly affected by silencing or overexpressing SOX5. ChIP assay revealed that SOX5 was bound to the MMP-9 promoter in RA-FLS. The overexpression of SOX5 markedly enhanced the MMP-9 promoter activity, and specific deletion of a putative SOX5-binding site in MMP-9 promoter diminished this promoter-driven transcription in FLS. Locally knocked down SOX5 inhibited MMP-9 expression in the joint tissue and reduced pannus migration and invasion into the cartilage in CIA mice. SOX5 plays a novel role in mediating migration and invasion of FLS in part by regulating MMP-9 expression in RA.

  20. Macrophage overexpression of matrix metalloproteinase-9 in aged mice improves diastolic physiology and cardiac wound healing after myocardial infarction.

    Science.gov (United States)

    Meschiari, Cesar A; Jung, Mira; Iyer, Rugmani Padmanabhan; Yabluchanskiy, Andriy; Toba, Hiroe; Garrett, Michael R; Lindsey, Merry L

    2018-02-01

    Matrix metalloproteinase (MMP)-9 increases in the myocardium with advanced age and after myocardial infarction (MI). Because young transgenic (TG) mice overexpressing human MMP-9 only in macrophages show better outcomes post-MI, whereas aged TG mice show a worse aging phenotype, we wanted to evaluate the effect of aging superimposed on MI to see if the detrimental effect of aging counteracted the benefits of macrophage MMP-9 overexpression. We used 17- to 28-mo-old male and female C57BL/6J wild-type (WT) and TG mice ( n = 10-21 mice/group) to evaluate the effects of aging superimposed on MI. Despite similar infarct areas and mortality rates at day 7 post-MI, aging TG mice showed improved diastolic properties and remodeling index compared with WT mice (both P wound healing through direct and indirect mechanisms to improve diastolic physiology and remodeling. NEW & NOTEWORTHY Aging mice with macrophage overexpression of matrix metalloproteinase-9 have increased macrophage numbers 7 days after myocardial infarction, resulting in improved diastolic physiology and left ventricular remodeling through effects on cardiac wound healing.