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Sample records for concentration-dependent manner engaging

  1. Paternal engagement during childbirth depending on the manner of their preparation.

    Science.gov (United States)

    Sioma-Markowska, Urszula; Poręba, Ryszard; Machura, Mariola; Skrzypulec-Plinta, Violetta

    2016-01-01

    The analysis of the forms of paternal activity depending on the manner of their preparation, including stages of labor. A prospective survey-based study involved 250 fathers who participated in their child's birth. The fathers included in the study were present during all stages of family-assisted natural labor. The study was conducted one day after childbirth with the use of a survey prepared by the authors. Statistical calculations were conducted using the Statistica PL software. The frequency of individual qualitative features (non-measurable) was assessed by means of a non-parametric χ² (chi-squared) test. The statistical significance level was p fathers included in the study (52.4%) participated in childbirth with no prior preparation. The dominant form of preparation involved self-education from books, magazines and the Internet (24%). 23.6% of fathers participated in ante-natal classes. The study demonstrated that fathers prepared for childbirth in ante-natal classes more often engaged in the supportive role, provided nursing care and carried out instrumental monitoring during each stage of childbirth. The fathers prepared for childbirth in ante-natal classes more often engage in the supportive role, provide nursing care and carry out instrumental control during each stage of childbirth. Ante-natal classes should be promoted as an optimal form of preparation for active participation in childbirth. Moreover, other forms of paternal ante-natal education as well as continued education in a delivery room should be developed.

  2. Intravenous infusion of docosahexaenoic acid increases serum concentrations in a dose-dependent manner and increases seizure latency in the maximal PTZ model.

    Science.gov (United States)

    Trépanier, Marc-Olivier; Kwong, Kei-Man; Domenichiello, Anthony F; Chen, Chuck T; Bazinet, Richard P; Burnham, W M

    2015-09-01

    Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (n-3 PUFA) that has been shown to raise seizure thresholds in the maximal pentylenetetrazole model following acute subcutaneous (s.c.) administration in rats. Following s.c. administration, however, the dose-response relationship for DHA has shown an inverted U-pattern. The purposes of the present experiment were as follows: (1) to determine the pattern of serum unesterified concentrations resulting from the intravenous (i.v.) infusions of various doses of DHA, (2) to determine the time course of these concentrations following the discontinuation of the infusions, and (3) to determine whether seizure protection in the maximal PTZ model would correlate with serum unesterified DHA levels. Animals received 5-minute i.v. infusions of saline or 25, 50, 100, or 200mg/kg of DHA via a cannula inserted into one of the tail veins. Blood was collected during and after the infusions by means of a second cannula inserted into the other tail vein (Experiment 1). A separate group of animals received saline or 12.5-, 25-, 50-, 100-, or 200 mg/kg DHA i.v. via a cannula inserted into one of the tail veins and were then seizure-tested in the maximal PTZ model either during infusion or after the discontinuation of the infusions. Slow infusions of DHA increased serum unesterified DHA concentrations in a dose-dependent manner, with the 200-mg/kg dose increasing the concentration approximately 260-fold compared with saline-infused animals. Following discontinuation of the infusions, serum concentrations rapidly dropped toward baseline, with half-lives of approximately 40 and 11s for the 25-mg/kg dose and 100-mg/kg dose, respectively. In the seizure-tested animals, DHA significantly increased latency to seizure onset in a dose-dependent manner. Following the discontinuation of infusion, seizure latency rapidly decreased toward baseline. Overall, our study suggests that i.v. infusion of unesterified DHA results in

  3. Alpha-amylase inhibitor, CS-1036 binds to serum amylase in a concentration-dependent and saturable manner.

    Science.gov (United States)

    Honda, Tomohiro; Kaneno-Urasaki, Yoko; Ito, Takashi; Kimura, Takako; Matsushima, Nobuko; Okabe, Hiromi; Yamasaki, Atsushi; Izumi, Takashi

    2014-03-01

    (2R,3R,4R)-4-hydroxy-2-(hydroxymethyl)pyrrolidin-3-yl 4-O-(6-deoxy-β-D-glucopyranosyl)-α-D-glucopyranoside (CS-1036), which is an α-amylase inhibitor, exhibited biphasic and sustained elimination with a long t1/2 (18.4-30.0 hours) in rats and monkeys, but exhibited a short t1/2 (3.7-7.9 hours) in humans. To clarify the species differences in the t1/2, the plasma protein binding of CS-1036 was evaluated by ultrafiltration. A concentration-dependent and saturable plasma protein binding of CS-1036 was observed in rats and monkeys with the dissociation rate constant (KD) of 8.95 and 27.2 nM, and maximal binding capacity (Bmax) of 52.8 and 22.1 nM, respectively. By the assessments of the recombinant amylase and immunoprecipitation, the major binding protein of CS-1036 in rats was identified as salivary amylase (KD 5.64 nM). CS-1036 also showed concentration-dependent and saturable binding to human salivary and pancreatic amylase, with similar binding affinity in rats. However, the protein binding of CS-1036 was constant in human plasma (≤10.2%) due to the lower serum amylase level compared with rats and monkeys. From the calculation of the unbound fraction (fu) in plasma based on in vitro KD and Bmax, the dose-dependent increase in fu after oral administration is speculated to lead to a dose-dependent increase in total body clearance and a high area under the curve/dose at lower doses, such as 0.3 mg/kg in rats.

  4. Tissue transglutaminase inhibits the TRPV5-dependent calcium transport in an N-glycosylation-dependent manner

    DEFF Research Database (Denmark)

    Boros, Sandor; Xi, Qi; Dimke, Henrik Anthony

    2011-01-01

    Tissue transglutaminase (tTG) is a multifunctional Ca(2+)-dependent enzyme, catalyzing protein crosslinking. The transient receptor potential vanilloid (TRPV) family of cation channels was recently shown to contribute to the regulation of TG activities in keratinocytes and hence skin barrier form......, these observations imply that tTG is a novel extracellular enzyme inhibiting the activity of TRPV5. The inhibition of TRPV5 occurs in an N-glycosylation-dependent manner, signifying a common final pathway by which distinct extracellular factors regulate channel activity....

  5. Azone® decreases the buccal mucosal permeation of Diazepam in a concentration-dependent manner via a reservoir effect

    DEFF Research Database (Denmark)

    Meng-Lund, Emil; Jacobsen, Jette; Jin, Liang

    2014-01-01

    The purpose of this study was to examine concentration-dependent effects of Azone® (AZ) on the buccal absorption of diazepam (DIAZ). Porcine buccal mucosa was placed in modified Ussing chambers and pretreated with 10 μL of 0%, 5%, 20%, and 50% (w/v) AZ in ethanol. DIAZ was administered to the don...

  6. Human, recombinant interleukin-2 induces in vitro histamine release in a dose-dependent manner

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Petersen, L J; Skov, P S

    1995-01-01

    significantly in the supernatant from cells stimulated by rIL-2 in a dose-dependent manner both in patients and volunteers. Total cell-bound histamine was 49.3 +/- 4.1 ng/ml in patients compared to 78.5 +/- 7.7 ng/ml in volunteers (p ... was significantly enhanced in cancer patients compared to volunteers (*p manner in both cancer patients and volunteers. This may in part explain the severe toxicity observed during high...

  7. Adiponectin influences progesterone production from MA-10 Leydig cells in a dose-dependent manner.

    Science.gov (United States)

    Landry, David; Paré, Aurélie; Jean, Stéphanie; Martin, Luc J

    2015-04-01

    Obesity in men is associated with lower testosterone levels, related to reduced sperm concentration and the development of various diseases with aging. Hormones produced by the adipose tissue may have influences on both metabolism and reproductive function. Among them, the production and secretion of adiponectin is inversely correlated to total body fat. Adiponectin receptors (AdipoR1 and AdipoR2) have been found to be expressed in testicular Leydig cells (producing testosterone). Since StAR and Cyp11a1 are essential for testosterone synthesis and adiponectin has been shown to regulate StAR mRNA in swine granulosa cells, we hypothesized that adiponectin might also regulate these genes in Leydig cells. Our objective was to determine whether adiponectin regulates StAR and Cyp11a1 genes in Leydig cells and to better define its mechanisms of action. Methods used in the current study are qPCR for the mRNA levels, transfections for promoter activities, and enzyme-linked immunosorbent assay for the progesterone concentration. We have found that adiponectin cooperates with cAMP-dependent stimulation to activate StAR and Cyp11a1 mRNA expressions in a dose-dependent manner in MA-10 Leydig cells as demonstrated by transfection of a luciferase reporter plasmid. These results led to a significant increase in progesterone production from MA-10 cells. Thus, our data suggest that high doses of adiponectin typical of normal body weight may promote testosterone production from Leydig cells.

  8. Fesselin is a target protein for calmodulin in a calcium-dependent manner

    International Nuclear Information System (INIS)

    KoIakowski, Janusz; Wrzosek, Antoni; Dabrowska, Renata

    2004-01-01

    Fesselin is a basic protein isolated from smooth muscle which binds G-actin and accelerates its polymerization as well as cross-links assembled filaments [J. Muscle Res. Cell Motil. 20 (1999) 539; Biochemistry 40 (2001) 14252]. In this report experimental evidence is provided for the first time proving that fesselin can interact with calmodulin in a Ca 2+ -dependent manner in vitro. Using ion exchange, followed by calmodulin-affinity chromatography, enabled us to simplify and shorten the fesselin preparation procedure and increase its yield by about three times in comparison to the procedure described by Leinweber et al. [J. Muscle Res. Cell Motil. 20 (1999) 539]. Fesselin interaction with dansyl-labelled calmodulin causes a 2-fold increase in maximum fluorescence intensity of the fluorophore and a 21 nm blue shift of the spectrum. The transition of complex formation between fesselin and calmodulin occurs at submicromolar concentration of calcium ions. The dissociation constant of fesselin Ca 2+ /calmodulin complexes amounted to 10 -8 M. The results suggest the existence of a direct link between Ca 2+ /calmodulin and fesselin at the level of actin cytoskeleton dynamics in smooth muscle

  9. Herp regulates Hrd1-mediated ubiquitylation in a ubiquitin-like domain-dependent manner

    DEFF Research Database (Denmark)

    Kny, Melanie; Standera, Sybille; Hartmann-Petersen, Rasmus

    2011-01-01

    in ER-associated protein degradation (ERAD) and interacts directly with the ubiquitin ligase Hrd1, which is found in high molecular mass complexes of the ER membrane. Here we present the first evidence that Herp regulates Hrd1-mediated ubiquitylation in a ubiquitin-like (UBL) domain-dependent manner. We...

  10. 29 CFR 794.103 - Dependence of exemption on engagement in described distribution.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Dependence of exemption on engagement in described distribution. 794.103 Section 794.103 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION... Act Scope and Application in General § 794.103 Dependence of exemption on engagement in described...

  11. L-carnosine affects the growth of Saccharomyces cerevisiae in a metabolism-dependent manner.

    Science.gov (United States)

    Cartwright, Stephanie P; Bill, Roslyn M; Hipkiss, Alan R

    2012-01-01

    The dipeptide L-carnosine (β-alanyl-L-histidine) has been described as enigmatic: it inhibits growth of cancer cells but delays senescence in cultured human fibroblasts and extends the lifespan of male fruit flies. In an attempt to understand these observations, the effects of L-carnosine on the model eukaryote, Saccharomyces cerevisiae, were examined on account of its unique metabolic properties; S. cerevisiae can respire aerobically, but like some tumor cells, it can also exhibit a metabolism in which aerobic respiration is down regulated. L-Carnosine exhibited both inhibitory and stimulatory effects on yeast cells, dependent upon the carbon source in the growth medium. When yeast cells were not reliant on oxidative phosphorylation for energy generation (e.g. when grown on a fermentable carbon source such as 2% glucose), 10-30 mM L-carnosine slowed growth rates in a dose-dependent manner and increased cell death by up to 17%. In contrast, in media containing a non-fermentable carbon source in which yeast are dependent on aerobic respiration (e.g. 2% glycerol), L-carnosine did not provoke cell death. This latter observation was confirmed in the respiratory yeast, Pichia pastoris. Moreover, when deletion strains in the yeast nutrient-sensing pathway were treated with L-carnosine, the cells showed resistance to its inhibitory effects. These findings suggest that L-carnosine affects cells in a metabolism-dependent manner and provide a rationale for its effects on different cell types.

  12. L-carnosine affects the growth of Saccharomyces cerevisiae in a metabolism-dependent manner.

    Directory of Open Access Journals (Sweden)

    Stephanie P Cartwright

    Full Text Available The dipeptide L-carnosine (β-alanyl-L-histidine has been described as enigmatic: it inhibits growth of cancer cells but delays senescence in cultured human fibroblasts and extends the lifespan of male fruit flies. In an attempt to understand these observations, the effects of L-carnosine on the model eukaryote, Saccharomyces cerevisiae, were examined on account of its unique metabolic properties; S. cerevisiae can respire aerobically, but like some tumor cells, it can also exhibit a metabolism in which aerobic respiration is down regulated. L-Carnosine exhibited both inhibitory and stimulatory effects on yeast cells, dependent upon the carbon source in the growth medium. When yeast cells were not reliant on oxidative phosphorylation for energy generation (e.g. when grown on a fermentable carbon source such as 2% glucose, 10-30 mM L-carnosine slowed growth rates in a dose-dependent manner and increased cell death by up to 17%. In contrast, in media containing a non-fermentable carbon source in which yeast are dependent on aerobic respiration (e.g. 2% glycerol, L-carnosine did not provoke cell death. This latter observation was confirmed in the respiratory yeast, Pichia pastoris. Moreover, when deletion strains in the yeast nutrient-sensing pathway were treated with L-carnosine, the cells showed resistance to its inhibitory effects. These findings suggest that L-carnosine affects cells in a metabolism-dependent manner and provide a rationale for its effects on different cell types.

  13. A QCM-D study of the concentration- and time-dependent interactions of human LL37 with model mammalian lipid bilayers.

    Science.gov (United States)

    Lozeau, Lindsay D; Rolle, Marsha W; Camesano, Terri A

    2018-07-01

    The human antimicrobial peptide LL37 is promising as an alternative to antibiotics due to its biophysical interactions with charged bacterial lipids. However, its clinical potential is limited due to its interactions with zwitterionic mammalian lipids leading to cytotoxicity. Mechanistic insight into the LL37 interactions with mammalian lipids may enable rational design of less toxic LL37-based therapeutics. To this end, we studied concentration- and time-dependent interactions of LL37 with zwitterionic model phosphatidylcholine (PC) bilayers with quartz crystal microbalance with dissipation (QCM-D). LL37 mass adsorption and PC bilayer viscoelasticity changes were monitored by measuring changes in frequency (Δf) and dissipation (ΔD), respectively. The Voigt-Kelvin viscoelastic model was applied to Δf and ΔD to study changes in bilayer thickness and density with LL37 concentration. At low concentrations (0.10-1.00 μM), LL37 adsorbed onto bilayers in a concentration-dependent manner. Further analyses of Δf, ΔD and thickness revealed that peptide saturation on the bilayers was a threshold for interactions observed above 2.00 μM, interactions that were rapid, multi-step, and reached equilibrium in a concentration- and time-dependent manner. Based on these data, we proposed a model of stable transmembrane pore formation at 2.00-10.0 μM, or transition from a primarily lipid to a primarily protein film with a transmembrane pore formation intermediate state at concentrations of LL37 > 10 μM. The concentration-dependent interactions between LL37 and PC bilayers correlated with the observed concentration-dependent biological activities of LL37 (antimicrobial, immunomodulatory and non-cytotoxic at 0.1-1.0 μM, hemolytic and some cytotoxicity at 2.0-13 μM and cytotoxic at >13 μM). Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Insulin is essential for in vitro chondrogenesis of mesenchymal progenitor cells and influences chondrogenesis in a dose-dependent manner.

    Science.gov (United States)

    Mueller, Michael B; Blunk, Torsten; Appel, Bernhard; Maschke, Angelika; Goepferich, Achim; Zellner, Johannes; Englert, Carsten; Prantl, Lukas; Kujat, Richard; Nerlich, Michael; Angele, Peter

    2013-01-01

    Insulin is a commonly used additive in chondrogenic media for differentiating mesenchymal stem cells (MSCs). The indispensability of other bioactive factors like TGF-β or dexamethasone in these medium formulations has been shown, but the role of insulin is unclear. The purpose of this study was to investigate whether insulin is essential for MSC chondrogenesis and if there is a dose-dependent effect of insulin on MSC chondrogenesis. We cultivated human MSCs in pellet culture in serum-free chondrogenic medium with insulin concentrations between 0 and 50 μg/ml and assessed the grade of chondrogenic differentiation by histological evaluation and determination of glycosaminoglycan (GAG), total collagen and DNA content. We further tested whether insulin can be delivered in an amount sufficient for MSC chondrogenesis via a drug delivery system in insulin-free medium. Chondrogenesis was not induced by standard chondrogenic medium without insulin and the expression of cartilage differentiation markers was dose-dependent at insulin concentrations between 0 and 10 μg/ml. An insulin concentration of 50 μg/ml had no additional effect compared with 10 μg/ml. Insulin was delivered by a release system into the cell culture under insulin-free conditions in an amount sufficient to induce chondrogenesis. Insulin is essential for MSC chondrogenesis in this system and chondrogenic differentiation is influenced by insulin in a dose-dependent manner. Insulin can be provided in a sufficient amount by a drug delivery system. Therefore, insulin is a suitable and inexpensive indicator substance for testing drug release systems in vitro.

  15. Alcohol Dependence and Altered Engagement of Neural Networks in Risky Decisions

    Directory of Open Access Journals (Sweden)

    Xi eZhu

    2016-03-01

    Full Text Available Alcohol dependence is associated with heightened risk tolerance and altered decision- making. This raises the question as to whether alcohol dependent patients (ADP are incapable of proper risk assessment. We investigated how healthy controls (HC and ADP engage neural networks to cope with the increased cognitive demands of risky decisions. We collected fMRI data while 34 HC and 16 ADP played a game that included safe and risky trials. In safe trials, participants accrued money at no risk of a penalty. In risky trials, reward and risk simultaneously increased as participants were instructed to decide when to stop a reward accrual period. If the participant failed to stop before an undisclosed time, the trial would bust and participants would not earn the money from that trial. Independent Component Analysis was used to identify networks engaged during the anticipation and the decision execution of risky compared with safe trials. Like HC, ADP demonstrated distinct network engagement for safe and risky trials at anticipation. However, at decision execution, ADP exhibited severely reduced discrimination in network engagement between safe and risky trials. Although ADP behaviorally responded to risk they failed to appropriately modify network engagement as the decision continued, leading ADP to assume similar network engagement regardless of risk prospects. This may reflect disorganized network switching and a facile response strategy uniformly adopted by ADP across risk conditions. We propose that aberrant salience network (SN engagement in ADP might contribute to ineffective network switching and that the role of the SN in risky decisions warrants further investigation.

  16. Student Engagement with a Flipped Classroom Teaching Design Affects Pharmacology Examination Performance in a Manner Dependent on Question Type

    Science.gov (United States)

    Naidu, Som; Yuriev, Elizabeth; Short, Jennifer L.; McLaughlin, Jacqueline E.; Larson, Ian C.

    2017-01-01

    Objective: To investigate the relationship between student engagement with the key elements of a flipped classroom approach (preparation and attendance), their attitudes to learning, including strategy development, and their performance on two types of examination questions (knowledge recall and providing rational predictions when faced with novel scenarios). Methods. This study correlated student engagement with the flipped classroom and student disposition to learning with student ability to solve novel scenarios in examinations. Results. Students who both prepared for and attended classes performed significantly better on examination questions that required analysis of novel scenarios compared to students who did not prepare and missed classes. However, there was no difference for both groups of students on examination questions that required knowledge and comprehension. Student motivation and use of strategies correlated with higher examination scores on questions requiring novel scenario analysis. Conclusion. There is a synergistic relationship between class preparation and attendance. The combination of preparation and attendance was positively correlated to assessment type; the relationship was apparent for questions requiring students to solve novel problems but not for questions requiring knowledge or comprehension. PMID:29302082

  17. Student Engagement with a Flipped Classroom Teaching Design Affects Pharmacology Examination Performance in a Manner Dependent on Question Type.

    Science.gov (United States)

    White, Paul J; Naidu, Som; Yuriev, Elizabeth; Short, Jennifer L; McLaughlin, Jacqueline E; Larson, Ian C

    2017-11-01

    Objective: To investigate the relationship between student engagement with the key elements of a flipped classroom approach (preparation and attendance), their attitudes to learning, including strategy development, and their performance on two types of examination questions (knowledge recall and providing rational predictions when faced with novel scenarios). Methods. This study correlated student engagement with the flipped classroom and student disposition to learning with student ability to solve novel scenarios in examinations. Results. Students who both prepared for and attended classes performed significantly better on examination questions that required analysis of novel scenarios compared to students who did not prepare and missed classes. However, there was no difference for both groups of students on examination questions that required knowledge and comprehension. Student motivation and use of strategies correlated with higher examination scores on questions requiring novel scenario analysis. Conclusion. There is a synergistic relationship between class preparation and attendance. The combination of preparation and attendance was positively correlated to assessment type; the relationship was apparent for questions requiring students to solve novel problems but not for questions requiring knowledge or comprehension.

  18. Cutaneous T cell lymphoma expresses immunosuppressive CD80 (B7-1) cell surface protein in a STAT5-dependent manner

    DEFF Research Database (Denmark)

    Zhang, Qian; Wang, Hong Yi; Wei, Fang

    2014-01-01

    as their joint ability to transcriptionally activate the CD80 gene. In IL-2-dependent CTCL cells, CD80 expression is induced by the cytokine in a Jak1/3- and STAT5a/b-dependent manner, whereas in the CTCL cells with constitutive STAT5 activation, CD80 expression is also STAT5a/b dependent but is independent......(+) and CD8(+) populations or the CD4(+) subset alone, transfected with CD152 mRNA, inhibits proliferation of normal T cells in a CD152- and CD80-dependent manner. These data identify a new mechanism of immune evasion in CTCL and suggest that the CD80-CD152 axis may become a therapeutic target in this type...

  19. Parp1 protects against Aag-dependent alkylation-induced nephrotoxicity in a sex-dependent manner.

    Science.gov (United States)

    Calvo, Jennifer A; Allocca, Mariacarmela; Fake, Kimberly R; Muthupalani, Sureshkumar; Corrigan, Joshua J; Bronson, Roderick T; Samson, Leona D

    2016-07-19

    Nephrotoxicity is a common toxic side-effect of chemotherapeutic alkylating agents. Although the base excision repair (BER) pathway is essential in repairing DNA alkylation damage, under certain conditions the initiation of BER produces toxic repair intermediates that damage healthy tissues. We have shown that the alkyladenine DNA glycosylase, Aag (a.k.a. Mpg), an enzyme that initiates BER, mediates alkylation-induced whole-animal lethality and cytotoxicity in the pancreas, spleen, retina, and cerebellum, but not in the kidney. Cytotoxicity in both wild-type and Aag-transgenic mice (AagTg) was abrogated in the absence of Poly(ADP-ribose) polymerase-1 (Parp1). Here we report that Parp1-deficient mice expressing increased Aag (AagTg/Parp1-/-) develop sex-dependent kidney failure upon exposure to the alkylating agent, methyl methanesulfonate (MMS), and suffer increased whole-animal lethality compared to AagTg and wild-type mice. Macroscopic, histological, electron microscopic and immunohistochemical analyses revealed morphological kidney damage including dilated tubules, proteinaceous casts, vacuolation, collapse of the glomerular tuft, and deterioration of podocyte structure. Moreover, mice exhibited clinical signs of kidney disease indicating functional damage, including elevated blood nitrogen urea and creatinine, hypoproteinemia and proteinuria. Pharmacological Parp inhibition in AagTg mice also resulted in sensitivity to MMS-induced nephrotoxicity. These findings provide in vivo evidence that Parp1 modulates Aag-dependent MMS-induced nephrotoxicity in a sex-dependent manner and highlight the critical roles that Aag-initiated BER and Parp1 may play in determining the side-effects of chemotherapeutic alkylating agents.

  20. Parental overprotection engenders dysfunctional attitudes about achievement and dependency in a gender-specific manner.

    Science.gov (United States)

    Otani, Koichi; Suzuki, Akihito; Matsumoto, Yoshihiko; Shibuya, Naoshi; Sadahiro, Ryoichi; Enokido, Masanori

    2013-12-24

    It has been suggested that dysfunctional attitudes, cognitive vulnerability to depression, have developmental origins. The present study examined the effects of parental rearing on dysfunctional attitudes in three areas of life with special attention to gender specificity. The subjects were 665 Japanese healthy volunteers. Dysfunctional attitudes were assessed by the 24-item Dysfunctional Attitude Scale, which has the Achievement, Dependency and Self-control subscales. Perceived parental rearing was assessed by the Parental Bonding Instrument, which has the Care and Protection subscales. Higher scores of the Achievement (β = 0.293, p overprotection engenders dysfunctional attitudes about achievement and dependency in a gender-specific manner.

  1. TALE activators regulate gene expression in a position- and strand-dependent manner in mammalian cells.

    Science.gov (United States)

    Uhde-Stone, Claudia; Cheung, Edna; Lu, Biao

    2014-01-24

    Transcription activator-like effectors (TALEs) are a class of transcription factors that are readily programmable to regulate gene expression. Despite their growing popularity, little is known about binding site parameters that influence TALE-mediated gene activation in mammalian cells. We demonstrate that TALE activators modulate gene expression in mammalian cells in a position- and strand-dependent manner. To study the effects of binding site location, we engineered TALEs customized to recognize specific DNA sequences located in either the promoter or the transcribed region of reporter genes. We found that TALE activators robustly activated reporter genes when their binding sites were located within the promoter region. In contrast, TALE activators inhibited the expression of reporter genes when their binding sites were located on the sense strand of the transcribed region. Notably, this repression was independent of the effector domain utilized, suggesting a simple blockage mechanism. We conclude that TALE activators in mammalian cells regulate genes in a position- and strand-dependent manner that is substantially different from gene activation by native TALEs in plants. These findings have implications for optimizing the design of custom TALEs for genetic manipulation in mammalian cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Acyl-CoA-binding protein (ACBP) localizes to the endoplasmic reticulum and Golgi in a ligand-dependent manner in mammalian cells

    DEFF Research Database (Denmark)

    Hansen, Jesper S; Færgeman, Nils J; Kragelund, Birthe B

    2008-01-01

    showed that ACBP targeted to the ER (endoplasmic reticulum) and Golgi in a ligand-binding-dependent manner. A variant Y28F/K32A-FACI-50, which is unable to bind acyl-CoA, did no longer show association with the ER and became segregated from the Golgi, as analysed by intensity correlation calculations....... Depletion of fatty acids from cells by addition of FAFBSA (fatty-acid-free BSA) significantly decreased FACI-50 association with the Golgi, whereas fatty acid overloading increased Golgi association, strongly supporting that ACBP associates with the Golgi in a ligand-dependent manner. FRAP (fluorescence...... recovery after photobleaching) showed that the fatty-acid-induced targeting of FACI-50 to the Golgi resulted in a 5-fold reduction in FACI-50 mobility. We suggest that ACBP is targeted to the ER and Golgi in a ligand-binding-dependent manner in living cells and propose that ACBP may be involved...

  3. Time- and concentration-dependent effects of resveratrol in HL-60 and HepG2 cells

    DEFF Research Database (Denmark)

    Stervbo, Ulrik; Vang, Ole; Bonnesen, Christine

    2006-01-01

    Resveratrol, a phytochemical present in grapes, has been demonstrated to inhibit tumourigenesis in animal models. However, the specific mechanism by which resveratrol exerts its anticarcinogenic effect has yet to be elucidated. In the present study, the inhibitory effects of resveratrol on cell...... proliferation and apoptosis were evaluated in the human leukaemia cell line HL-60 and the human hepatoma derived cell line HepG2. We found that after a 2 h incubation period, resveratrol inhibited DNA synthesis in a concentration-dependent manner. The IC50 value was 15 μM in both HL-60 and HepG2 cells. When...... the time of treatment was extended, an increase in IC50 value was observed; for example, at 24 h the IC50 value was 30 μM for HL-60 cells and 60 μM for HepG2 cells. Flow cytometry revealed that cells accumulated in different phases of the cell cycle depending on the resveratrol concentration. Furthermore...

  4. Molecular Stress-inducing Compounds Increase Osteoclast Formation in a Heat Shock Factor 1 Protein-dependent Manner*

    Science.gov (United States)

    Chai, Ryan C.; Kouspou, Michelle M.; Lang, Benjamin J.; Nguyen, Chau H.; van der Kraan, A. Gabrielle J.; Vieusseux, Jessica L.; Lim, Reece C.; Gillespie, Matthew T.; Benjamin, Ivor J.; Quinn, Julian M. W.; Price, John T.

    2014-01-01

    Many anticancer therapeutic agents cause bone loss, which increases the risk of fractures that severely reduce quality of life. Thus, in drug development, it is critical to identify and understand such effects. Anticancer therapeutic and HSP90 inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) causes bone loss by increasing osteoclast formation, but the mechanism underlying this is not understood. 17-AAG activates heat shock factor 1 (Hsf1), the master transcriptional regulator of heat shock/cell stress responses, which may be involved in this negative action of 17-AAG upon bone. Using mouse bone marrow and RAW264.7 osteoclast differentiation models we found that HSP90 inhibitors that induced a heat shock response also enhanced osteoclast formation, whereas HSP90 inhibitors that did not (including coumermycin A1 and novobiocin) did not affect osteoclast formation. Pharmacological inhibition or shRNAmir knockdown of Hsf1 in RAW264.7 cells as well as the use of Hsf1 null mouse bone marrow cells demonstrated that 17-AAG-enhanced osteoclast formation was Hsf1-dependent. Moreover, ectopic overexpression of Hsf1 enhanced 17-AAG effects upon osteoclast formation. Consistent with these findings, protein levels of the essential osteoclast transcription factor microphthalmia-associated transcription factor were increased by 17-AAG in an Hsf1-dependent manner. In addition to HSP90 inhibitors, we also identified that other agents that induced cellular stress, such as ethanol, doxorubicin, and methotrexate, also directly increased osteoclast formation, potentially in an Hsf1-dependent manner. These results, therefore, indicate that cellular stress can enhance osteoclast differentiation via Hsf1-dependent mechanisms and may significantly contribute to pathological and therapeutic related bone loss. PMID:24692538

  5. Molecular stress-inducing compounds increase osteoclast formation in a heat shock factor 1 protein-dependent manner.

    Science.gov (United States)

    Chai, Ryan C; Kouspou, Michelle M; Lang, Benjamin J; Nguyen, Chau H; van der Kraan, A Gabrielle J; Vieusseux, Jessica L; Lim, Reece C; Gillespie, Matthew T; Benjamin, Ivor J; Quinn, Julian M W; Price, John T

    2014-05-09

    Many anticancer therapeutic agents cause bone loss, which increases the risk of fractures that severely reduce quality of life. Thus, in drug development, it is critical to identify and understand such effects. Anticancer therapeutic and HSP90 inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) causes bone loss by increasing osteoclast formation, but the mechanism underlying this is not understood. 17-AAG activates heat shock factor 1 (Hsf1), the master transcriptional regulator of heat shock/cell stress responses, which may be involved in this negative action of 17-AAG upon bone. Using mouse bone marrow and RAW264.7 osteoclast differentiation models we found that HSP90 inhibitors that induced a heat shock response also enhanced osteoclast formation, whereas HSP90 inhibitors that did not (including coumermycin A1 and novobiocin) did not affect osteoclast formation. Pharmacological inhibition or shRNAmir knockdown of Hsf1 in RAW264.7 cells as well as the use of Hsf1 null mouse bone marrow cells demonstrated that 17-AAG-enhanced osteoclast formation was Hsf1-dependent. Moreover, ectopic overexpression of Hsf1 enhanced 17-AAG effects upon osteoclast formation. Consistent with these findings, protein levels of the essential osteoclast transcription factor microphthalmia-associated transcription factor were increased by 17-AAG in an Hsf1-dependent manner. In addition to HSP90 inhibitors, we also identified that other agents that induced cellular stress, such as ethanol, doxorubicin, and methotrexate, also directly increased osteoclast formation, potentially in an Hsf1-dependent manner. These results, therefore, indicate that cellular stress can enhance osteoclast differentiation via Hsf1-dependent mechanisms and may significantly contribute to pathological and therapeutic related bone loss.

  6. dSir2 in the Adult Fat Body, but Not in Muscles, Regulates Life Span in a Diet-Dependent Manner

    Directory of Open Access Journals (Sweden)

    Kushal Kr. Banerjee

    2012-12-01

    Full Text Available Sir2, an evolutionarily conserved NAD+-dependent deacetylase, has been implicated as a key factor in mediating organismal life span. However, recent contradictory findings have brought into question the role of Sir2 and its orthologs in regulating organismal longevity. In this study, we report that Drosophila Sir2 (dSir2 in the adult fat body regulates longevity in a diet-dependent manner. We used inducible Gal4 drivers to knock down and overexpress dSir2 in a tissue-specific manner. A diet-dependent life span phenotype of dSir2 perturbations (both knockdown and overexpression in the fat body, but not muscles, negates the effects of background genetic mutations. In addition to providing clarity to the field, our study contrasts the ability of dSir2 in two metabolic tissues to affect longevity. We also show that dSir2 knockdown abrogates fat-body dFOXO-dependent life span extension. This report highlights the importance of the interplay between genetic factors and dietary inputs in determining organismal life spans.

  7. The effect of points and audio on concentration, engagement, enjoyment, learning, motivation, and classroom dynamics using Kahoot!

    DEFF Research Database (Denmark)

    Wang, Alf Inge; Lieberoth, Andreas

    2016-01-01

    There are many examples on the use of game-based learning in and outside the classroom, along with evaluation of their effect in terms of engagement, learning, classroom dynamics, concentration, motivation and enjoyment. Most of the research in this area focuses on evaluations of the use of game...... that produce a positive effect on engagement, motivation, enjoyment, concentration, classroom dynamics and learning. In this paper, we present an experiment where we investigated how the use of points and audio affect the learning environment. Specifically, the paper presents results from an experiment where...... points and audio. The results from the experiment reveal that there are some significant differences whether audio and points are used in game-based learning in the areas of concentration, engagement, enjoyment, and motivation. The most surprising finding was how the classroom dynamics was positively...

  8. Biochanin a and Daidzein Influence Meiotic Maturation of Pig Oocytes in a Different Manner

    Directory of Open Access Journals (Sweden)

    Hošková K.

    2014-09-01

    Full Text Available The aim of the study was to determine the influence of different concentrations of phytoestrogens biochanin A (BIO A; 20, 40, 50μg ml-1 and daidzein (DAI; 10, 20, 40, 50μg ml-1 on the course of meiotic maturation of pig oocytes. After a 24-hour cultivation, a stage of nuclear maturation was achieved and the areas of cumulus-oocyte complexes (COCs, as an indicator of cumulus expansion, were evaluated. The effects of both contaminants on oocytes were mani - fested from the lowest concentration used. Nuclear maturation was inhibited in a dose-dependent manner in the case of BIO A. Effects of DAI reached a plateau at a concentration of 20μg ml-1.Possible relationship to limited solubility of DAI was excluded because limits of DAI solubility in culture medium were confirmed at 50 μg ml-1.The cumulus expansion was also influenced in a different manner - reduction of the COC’s area by BIO A was dose-dependent, whereas DAI had the strongest effect on CCs in the lowest and highest concentrations used. Both phytoestrogens negatively influence the meiotic maturation of porcine oocytes but there are significant differences in their concrete effects which could relate to the diverse mechanisms of their acting on target cells.

  9. PAI-1 modulates cell migration in a LRP1-dependent manner via β-catenin and ERK1/2

    DEFF Research Database (Denmark)

    Kozlova, Nina; Jensen, Jan Kristian; Chi, Tabughang Franklin

    2015-01-01

    was proposed to modulate the β-catenin pathway. Therefore, we used wild-type mouse embryonic fibroblasts (MEFs), and MEFs deficient of LRP1 to study PAI-1 as modulator of the β-catenin pathway. We found that PAI-1 influences MEF proliferation and motility in a LRP1-dependent manner and that β...

  10. The positional identity of iPSC-derived neural progenitor cells along the anterior-posterior axis is controlled in a dosage-dependent manner by bFGF and EGF

    DEFF Research Database (Denmark)

    Zhou, Shuling; Ochalek, Anna; Szczesna, Karolina

    2016-01-01

    Neural rosettes derived from human induced pluripotent stem cells (iPSCs) have been claimed to be a highly robust in vitro cellular model for biomedical application. They are able to propagate in vitro in the presence of mitogens, including basic fibroblast growth factor (bFGF) and epidermal growth...... factor (EGF). However, these two mitogens are also involved in anterior-posterior patterning in a gradient dependent manner along the neural tube axis. Here, we compared the regional identity of neural rosette cells and specific neural subtypes of their progeny propagated with low and high concentrations...... of the neural rosettes, resulting in subsequent cholinergic neuron differentiation. Thus, our results indicate that different concentrations of bFGF and EGF supplemented during propagation of neural rosettes are involved in altering the identity of the resultant neural cells....

  11. GSK3β is involved in the relief of mitochondria pausing in a Tau-dependent manner.

    Directory of Open Access Journals (Sweden)

    María Llorens-Martín

    Full Text Available Mitochondrial trafficking deficits have been implicated in the pathogenesis of several neurological diseases, including Alzheimer's disease (AD. The Ser/Thre kinase GSK3β is believed to play a fundamental role in AD pathogenesis. Given that GSK3β substrates include Tau protein, here we studied the impact of GSK3β on mitochondrial trafficking and its dependence on Tau protein. Overexpression of GSK3β in neurons resulted in an increase in motile mitochondria, whereas a decrease in the activity of this kinase produced an increase in mitochondria pausing. These effects were dependent on Tau proteins, as Tau (-/- neurons did not respond to distinct GSK3β levels. Furthermore, differences in GSK3β expression did not affect other parameters like mitochondria velocity or mitochondria run length. We conclude that GSK3B activity regulates mitochondrial axonal trafficking largely in a Tau-dependent manner.

  12. 26 CFR 1.881-1 - Manner of taxing foreign corporations.

    Science.gov (United States)

    2010-04-01

    ... tax avoidance purposes, whether or not such corporation is engaged in trade or business in the United... TAX (CONTINUED) INCOME TAXES Foreign Corporations § 1.881-1 Manner of taxing foreign corporations. (a) Classes of foreign corporations. For purposes of the income tax, foreign corporations are divided into two...

  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. Diffusion-controlled reaction. V. Effect of concentration-dependent diffusion coefficient on reaction rate in graft polymerization

    International Nuclear Information System (INIS)

    Imre, K.; Odian, G.

    1979-01-01

    The effect of diffusion on radiation-initiated graft polymerization has been studied with emphasis on the single- and two-penetrant cases. When the physical properties of the penetrants are similar, the two-penetrant problems can be reduced to the single-penetrant problem by redefining the characteristic parameters of the system. The diffusion-free graft polymerization rate is assumed to be proportional to the upsilon power of the monomer concentration respectively, and, in which the proportionality constant a = k/sub p/R/sub i//sup w//k/sub t//sup z/, where k/sub p/ and k/sub t/ are the propagation and termination rate constants, respectively, and R/sub i/ is the initiation rate. The values of upsilon, w, and z depend on the particular reaction system. The results of earlier work were generalized by allowing a non-Fickian diffusion rate which predicts an essentially exponential dependence on the monomer concentration of the diffusion coefficient, D = D 0 [exp(deltaC/M)], where M is the saturation concentration. A reaction system is characterized by the three dimensionless parameters, upsilon, delta, and A = (L/2)[aM/sup (upsilon--1)//D 0 ]/sup 1/2/, where L is the polymer film thickness. Graft polymerization tends to become diffusion controlled as A increases. Larger values of delta and ν cause a reaction system to behave closer to the diffusion-free regime. Transition from diffusion-free to diffusion-controlled reaction involves changes in the dependence of the reaction rate on film thickness, initiation rate, and monomer concentration. Although the diffusion-free rate is w order in initiation rate, upsilon order in monomer, and independent of film thickness, the diffusion-controlled rate is w/2 order in initiator rate and inverse first-order in film thickness. Dependence of the diffusion-controlled rate on monomer is dependent in a complex manner on the diffusional characteristics of the reaction system. 11 figures, 4 tables

  15. Ecklonia cava Polyphenol Has a Protective Effect against Ethanol-Induced Liver Injury in a Cyclic AMP-Dependent Manner

    Directory of Open Access Journals (Sweden)

    Haruka Yamashita

    2015-06-01

    Full Text Available Previously, we showed that Ecklonia cava polyphenol (ECP treatment suppressed ethanol-induced increases in hepatocyte death by scavenging intracellular reactive oxygen species (ROS and maintaining intracellular glutathione levels. Here, we examined the effects of ECP on the activities of alcohol-metabolizing enzymes and their regulating mechanisms in ethanol-treated hepatocytes. Isolated hepatocytes were incubated with or without 100 mM ethanol. ECP was dissolved in dimethylsulfoxide. ECP was added to cultured cells that had been incubated with or without ethanol. The cells were incubated for 0–24 h. In cultured hepatocytes, the ECP treatment with ethanol inhibited cytochrome P450 2E1 (CYP2E1 expression and activity, which is related to the production of ROS when large quantities of ethanol are oxidized. On the other hand, ECP treatment with ethanol increased the activity of alcohol dehydrogenase (ADH and aldehyde dehydrogenase. These changes in activities of CYP2E1 and ADH were suppressed by treatment with H89, an inhibitor of protein kinase A. ECP treatment with ethanol enhanced cyclic AMP concentrations compared with those of control cells. ECP may be a candidate for preventing ethanol-induced liver injury via regulating alcohol metabolic enzymes in a cyclic AMP-dependent manner.

  16. HDAC inhibition modulates hippocampus-dependent long-term memory for object location in a CBP-dependent manner

    Science.gov (United States)

    Haettig, Jakob; Stefanko, Daniel P.; Multani, Monica L.; Figueroa, Dario X.; McQuown, Susan C.; Wood, Marcelo A.

    2011-01-01

    Transcription of genes required for long-term memory not only involves transcription factors, but also enzymatic protein complexes that modify chromatin structure. Chromatin-modifying enzymes, such as the histone acetyltransferase (HAT) CREB (cyclic-AMP response element binding) binding protein (CBP), are pivotal for the transcriptional regulation required for long-term memory. Several studies have shown that CBP and histone acetylation are necessary for hippocampus-dependent long-term memory and hippocampal long-term potentiation (LTP). Importantly, every genetically modified Cbp mutant mouse exhibits long-term memory impairments in object recognition. However, the role of the hippocampus in object recognition is controversial. To better understand how chromatin-modifying enzymes modulate long-term memory for object recognition, we first examined the role of the hippocampus in retrieval of long-term memory for object recognition or object location. Muscimol inactivation of the dorsal hippocampus prior to retrieval had no effect on long-term memory for object recognition, but completely blocked long-term memory for object location. This was consistent with experiments showing that muscimol inactivation of the hippocampus had no effect on long-term memory for the object itself, supporting the idea that the hippocampus encodes spatial information about an object (such as location or context), whereas cortical areas (such as the perirhinal or insular cortex) encode information about the object itself. Using location-dependent object recognition tasks that engage the hippocampus, we demonstrate that CBP is essential for the modulation of long-term memory via HDAC inhibition. Together, these results indicate that HDAC inhibition modulates memory in the hippocampus via CBP and that different brain regions utilize different chromatin-modifying enzymes to regulate learning and memory. PMID:21224411

  17. Exercise training protects against aging-induced mitochondrial fragmentation in mouse skeletal muscle in a PGC-1α dependent manner

    DEFF Research Database (Denmark)

    Halling, Jens Frey; Jørgensen, Stine Ringholm; Olesen, Jesper

    2017-01-01

    Aging is associated with impaired mitochondrial function, whereas exercise training enhances mitochondrial content and function in part through activation of PGC-1α. Mitochondria form dynamic networks regulated by fission and fusion with profound effects on mitochondrial functions, yet the effect...... evidence that exercise training rescues aging-induced mitochondrial fragmentation in skeletal muscle by suppressing mitochondrial fission protein expression in a PGC-1α dependent manner....

  18. The effects of aspirin on platelet function and lysophosphatidic acids depend on plasma concentrations of EPA and DHA.

    Science.gov (United States)

    Block, Robert C; Abdolahi, Amir; Tu, Xin; Georas, Steve N; Brenna, J Thomas; Phipps, Richard P; Lawrence, Peter; Mousa, Shaker A

    2015-05-01

    Aspirin's prevention of cardiovascular disease (CVD) events in individuals with type 2 diabetes mellitus is controversial. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and aspirin all affect the cyclooxygenase enzyme. The relationship between plasma EPA and DHA and aspirin's effects has not been determined. Thirty adults with type 2 diabetes mellitus ingested aspirin (81 mg/day) for 7 days, then EPA+DHA (2.6g/day) for 28 days, then both for another 7 days. Lysophosphatidic acid (LPA) species and more classic platelet function outcomes were determined. Plasma concentrations of total EPA+DHA were associated with 7-day aspirin reduction effects on these outcomes in a "V"-shaped manner for all 11 LPA species and ADP-induced platelet aggregation. This EPA+DHA concentration was quite consistent for each of the LPA species and ADP. These results support aspirin effects on lysolipid metabolism and platelet aggregation depending on plasma EPA+DHA concentrations in individuals with a disturbed lipid milieu. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Maternal prenatal cortisol predicts infant negative emotionality in a sex-dependent manner.

    Science.gov (United States)

    Braithwaite, Elizabeth C; Pickles, Andrew; Sharp, Helen; Glover, Vivette; O'Donnell, Kieran J; Tibu, Florin; Hill, Jonathan

    2017-06-01

    Prenatal stress influences fetal developmental trajectories, which may implicate glucocorticoid mechanisms. There is also emerging evidence that effects of prenatal stress on offspring development are sex-dependent. However, little is known about the prospective relationship between maternal prenatal cortisol levels and infant behaviour, and whether it may be different in male and female infants. We sought to address this question using data from a prospective longitudinal cohort, stratified by risk. The Wirral Child Health and Development Study (WCHADS) cohort (n=1233) included a stratified random sub-sample (n=216) who provided maternal saliva samples, assayed for cortisol, at home over two days at 32weeks of pregnancy (on waking, 30-min post-waking and during the evening) and a measure of infant negative emotionality from the Neonatal Behavioural Assessment Scale (NBAS) at five weeks-of-age. General population estimates of associations among measures were obtained using inverse probability weights. Maternal prenatal cortisol sampled on waking predicted infant negative emotionality in a sex-dependent manner (interaction term, p=0.005); female infants exposed to high levels of prenatal cortisol were more negative (Beta=0.440, p=0.042), whereas male infants were less negative (Beta=-0.407, p=0.045). There was no effect of the 30-min post-waking measure or evening cortisol. Our findings add to an emerging body of work that has highlighted sex differences in fetal programming, whereby females become more reactive following prenatal stress, and males less reactive. A more complete understanding of sex-specific developmental trajectories in the context of prenatal stress is essential for the development of targeted prevention strategies. Copyright © 2017. Published by Elsevier Inc.

  20. Fentanyl activates hypoxia-inducible factor 1 in neuronal SH-SY5Y cells and mice under non-hypoxic conditions in a μ-opioid receptor-dependent manner.

    Science.gov (United States)

    Daijo, Hiroki; Kai, Shinichi; Tanaka, Tomoharu; Wakamatsu, Takuhiko; Kishimoto, Shun; Suzuki, Kengo; Harada, Hiroshi; Takabuchi, Satoshi; Adachi, Takehiko; Fukuda, Kazuhiko; Hirota, Kiichi

    2011-09-30

    Hypoxia-inducible factor 1 (HIF-1) is the main transcription factor responsible for hypoxia-induced gene expression. Perioperative drugs including anesthetics have been reported to affect HIF-1 activity. However, the effect of fentanyl on HIF-1 activity is not well documented. In this study, we investigated the effect of fentanyl and other opioids on HIF-1 activity in human SH-SY5Y neuroblastoma cells, hepatoma Hep3B cells, lung adenocarcinoma A549 cells and mice. Cells were exposed to fentanyl, and HIF-1 protein expression was examined by Western blot analysis using anti-HIF-1α and β antibodies. HIF-1-dependent gene expression was investigated by semi-quantitative real-time reverse transcriptase (RT)-PCR (qRT-PCR) and luciferase assay. Furthermore, fentanyl was administered intraperitoneally and HIF-1-dependent gene expression was investigated by qRT-PCR in the brains and kidneys of mice. A 10-μM concentration of fentanyl and other opioids, including 1 μM morphine and 4 μM remifentanil, induced HIF-1α protein expression and HIF-1 target gene expression in an opioid receptor-dependent manner in SH-SY5Y cells with activity peaking at 24h. Fentanyl did not augment HIF-1α expression during hypoxia-induced induction. HIF-1α stabilization assays and experiments with cycloheximide revealed that fentanyl increased translation from HIF-1α mRNA but did not stabilize the HIF-1α protein. Furthermore, fentanyl induced HIF-1 target gene expression in the brains of mice but not in their kidneys in a naloxone-sensitive manner. In this report, we describe for the first time that fentanyl, both in vitro and in vivo, induces HIF-1 activation under non-hypoxic conditions, leading to increases in expression of genes associated with adaptation to hypoxia. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. An endocrine disruptor, bisphenol A, affects development in the protochordate Ciona intestinalis: Hatching rates and swimming behavior alter in a dose-dependent manner

    International Nuclear Information System (INIS)

    Matsushima, Ayami; Ryan, Kerrianne; Shimohigashi, Yasuyuki; Meinertzhagen, Ian A.

    2013-01-01

    Bisphenol A (BPA) is widely used industrially to produce polycarbonate plastics and epoxy resins. Numerous studies document the harmful effects caused by low-dose BPA exposure especially on nervous systems and behavior in experimental animals such as mice and rats. Here, we exposed embryos of a model chordate, Ciona intestinalis, to seawater containing BPA to evaluate adverse effects on embryonic development and on the swimming behavior of subsequent larvae. Ciona is ideal because its larva develops rapidly and has few cells. The rate of larval hatching decreased in a dose-dependent manner with exposures to BPA above 3 μM; swimming behavior was also affected in larvae emerging from embryos exposed to 1 μM BPA. Adverse effects were most severe on fertilized eggs exposed to BPA within 7 h post-fertilization. Ciona shares twelve nuclear receptors with mammals, and BPA is proposed to disturb the physiological functions of one or more of these. - Highlights: ► Embryos of Ciona intestinalis were exposed to BPA to evaluate its developmental effects. ► The rate of larval hatching decreased in a dose-dependent manner. ► Swimming behavior was affected in larvae that emerge from embryos exposed to 1 μM BPA. ► Our findings will support a new strategy to analyze the developmental effects induced by BPA. - Exposure of fertilized Ciona embryos to BPA decreased their hatch rate in a dose-dependent manner and led to abnormal larval swimming behavior.

  2. AtPP2CG1, a protein phosphatase 2C, positively regulates salt tolerance of Arabidopsis in abscisic acid-dependent manner

    International Nuclear Information System (INIS)

    Liu, Xin; Zhu, Yanming; Zhai, Hong; Cai, Hua; Ji, Wei; Luo, Xiao; Li, Jing; Bai, Xi

    2012-01-01

    Highlights: ► AtPP2CG1 positively regulates salt tolerance in ABA-dependent manner. ► AtPP2CG1 up-regulates the expression of marker genes in different pathways. ► AtPP2CG1 expresses in the vascular system and trichomes of Arabidopsis. -- Abstract: AtPP2CG1 (Arabidopsis thaliana protein phosphatase 2C G Group 1) was predicted as an abiotic stress candidate gene by bioinformatic analysis in our previous study. The gene encodes a putative protein phosphatase 2C that belongs to Group G of PP2C. There is no report of Group G genes involved in abiotic stress so far. Real-time RT-PCR analysis showed that AtPP2CG1 expression was induced by salt, drought, and abscisic acid (ABA) treatment. The expression levels of AtPP2CG1 in the ABA synthesis-deficient mutant abi2–3 were much lower than that in WT plants under salt stress suggesting that the expression of AtPP2CG1 acts in an ABA-dependent manner. Over-expression of AtPP2CG1 led to enhanced salt tolerance, whereas its loss of function caused decreased salt tolerance. These results indicate that AtPP2CG1 positively regulates salt stress in an ABA-dependent manner. Under salt treatment, AtPP2CG1 up-regulated the expression levels of stress-responsive genes, including RD29A, RD29B, DREB2A and KIN1. GUS activity was detected in roots, leaves, stems, flower, and trichomes of AtPP2CG1 promoter–GUS transgenic plants. AtPP2CG1 protein was localized in nucleus and cytoplasm via AtPP2CG1:eGFP and YFP:AtPP2CG1 fusion approaches.

  3. AtPP2CG1, a protein phosphatase 2C, positively regulates salt tolerance of Arabidopsis in abscisic acid-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xin, E-mail: fangfei6073@126.com [Plant Bioengineering Laboratory, Northeast Agricultural University, Harbin 150030 (China); Zhu, Yanming, E-mail: ymzhu2001@neau.edu.cn [Plant Bioengineering Laboratory, Northeast Agricultural University, Harbin 150030 (China); Zhai, Hong, E-mail: Zhai.h@neigaehrb.ac.cn [Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Harbin 150040 (China); Cai, Hua, E-mail: small-big@sohu.com [Plant Bioengineering Laboratory, Northeast Agricultural University, Harbin 150030 (China); Ji, Wei, E-mail: iwei_j@hotmail.com [Plant Bioengineering Laboratory, Northeast Agricultural University, Harbin 150030 (China); Luo, Xiao, E-mail: luoxiao2010@yahoo.cn [Plant Bioengineering Laboratory, Northeast Agricultural University, Harbin 150030 (China); Li, Jing, E-mail: lijing@neau.edu.cn [Plant Secondary Metabolism Laboratory, Northeast Agricultural University, Harbin 150030 (China); Bai, Xi, E-mail: baixi@neau.edu.cn [Plant Bioengineering Laboratory, Northeast Agricultural University, Harbin 150030 (China)

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer AtPP2CG1 positively regulates salt tolerance in ABA-dependent manner. Black-Right-Pointing-Pointer AtPP2CG1 up-regulates the expression of marker genes in different pathways. Black-Right-Pointing-Pointer AtPP2CG1 expresses in the vascular system and trichomes of Arabidopsis. -- Abstract: AtPP2CG1 (Arabidopsis thaliana protein phosphatase 2C G Group 1) was predicted as an abiotic stress candidate gene by bioinformatic analysis in our previous study. The gene encodes a putative protein phosphatase 2C that belongs to Group G of PP2C. There is no report of Group G genes involved in abiotic stress so far. Real-time RT-PCR analysis showed that AtPP2CG1 expression was induced by salt, drought, and abscisic acid (ABA) treatment. The expression levels of AtPP2CG1 in the ABA synthesis-deficient mutant abi2-3 were much lower than that in WT plants under salt stress suggesting that the expression of AtPP2CG1 acts in an ABA-dependent manner. Over-expression of AtPP2CG1 led to enhanced salt tolerance, whereas its loss of function caused decreased salt tolerance. These results indicate that AtPP2CG1 positively regulates salt stress in an ABA-dependent manner. Under salt treatment, AtPP2CG1 up-regulated the expression levels of stress-responsive genes, including RD29A, RD29B, DREB2A and KIN1. GUS activity was detected in roots, leaves, stems, flower, and trichomes of AtPP2CG1 promoter-GUS transgenic plants. AtPP2CG1 protein was localized in nucleus and cytoplasm via AtPP2CG1:eGFP and YFP:AtPP2CG1 fusion approaches.

  4. L-Arginine Enhances Protein Synthesis by Phosphorylating mTOR (Thr 2446 in a Nitric Oxide-Dependent Manner in C2C12 Cells

    Directory of Open Access Journals (Sweden)

    Ruxia Wang

    2018-01-01

    Full Text Available Muscle atrophy may arise from many factors such as inactivity, malnutrition, and inflammation. In the present study, we investigated the stimulatory effect of nitric oxide (NO on muscle protein synthesis. Primarily, C2C12 cells were supplied with extra L-arginine (L-Arg in the culture media. L-Arg supplementation increased the activity of inducible nitric oxide synthase (iNOS, the rate of protein synthesis, and the phosphorylation of mTOR (Thr 2446 and p70S6K (Thr 389. L-NAME, an NOS inhibitor, decreased NO concentrations within cells and abolished the stimulatory effect of L-Arg on protein synthesis and the phosphorylation of mTOR and p70S6K. In contrast, SNP (sodium nitroprusside, an NO donor, increased NO concentrations, enhanced protein synthesis, and upregulated mTOR and p70S6K phosphorylation, regardless of L-NAME treatment. Blocking mTOR with rapamycin abolished the stimulatory effect of both L-Arg and SNP on protein synthesis and p70S6K phosphorylation. These results indicate that L-Arg stimulates protein synthesis via the activation of the mTOR (Thr 2446/p70S6K signaling pathway in an NO-dependent manner.

  5. Magnesium sulfate differentially modulates fetal membrane inflammation in a time-dependent manner.

    Science.gov (United States)

    Cross, Sarah N; Nelson, Rachel A; Potter, Julie A; Norwitz, Errol R; Abrahams, Vikki M

    2018-04-30

    Chorioamnionitis and infection-associated inflammation are major causes of preterm birth. Magnesium sulfate (MgSO 4 ) is widely used in obstetrics as a tocolytic; however, its mechanism of action is unclear. This study sought to investigate how MgSO 4 modulates infection-associated inflammation in fetal membranes (FMs), and whether the response was time dependent. Human FM explants were treated with or without bacterial lipopolysaccharide (LPS); with or without MgSO 4 added either: 1 hour before LPS; at the same time as LPS; 1 hour post-LPS; or 2 hours post-LPS. Explants were also treated with or without viral dsRNA and LPS, alone or in combination; and MgSO 4 added 1 hour post-LPS After 24 hours, supernatants were measured for cytokines/chemokines; and tissue lysates measured for caspase-1 activity. Lipopolysaccharide-induced FM inflammation by upregulating the secretion of a number of inflammatory cytokines/chemokines. Magnesium sulfate administered 1-hour post-LPS inhibited FM secretion of IL-1β, IL-6, G-CSF, RANTES, and TNFα. Magnesium sulfate administered 2 hours post-LPS augmented FM secretion of these factors as well as IL-8, IFNγ, VEGF, GROα and IP-10. Magnesium sulfate delivered 1- hour post-LPS inhibited LPS-induced caspase-1 activity, and inhibited the augmented IL-1β response triggered by combination viral dsRNA and LPS. Magnesium sulfate differentially modulates LPS-induced FM inflammation in a time-dependent manner, in part through its modulation of caspase-1 activity. Thus, the timing of MgSO 4 administration may be critical in optimizing its anti-inflammatory effects in the clinical setting. MgSO 4 might also be useful at preventing FM inflammation triggered by a polymicrobial viral-bacterial infection. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Psychological and physiological stress negatively impacts early engagement and retention of opioid-dependent individuals on methadone maintenance.

    Science.gov (United States)

    Jaremko, Kellie M; Sterling, Robert C; Van Bockstaele, Elisabeth J

    2015-01-01

    The present study investigated whether psychological and/or physiological measures of stress would impede induction onto methadone maintenance and predict early (scale (PSS) and post-traumatic stress disorder checklist (PCLC); 60% exhibited abnormal cortisol. Addiction severity index (ASI), drug-use, and stress indices explained between 17 and 37% of the variance in engagement including attendance, opioid abstinence, and methadone stabilization. Participants who discontinued treatment displayed poor engagement, abnormal cortisol, elevated withdrawal symptoms, higher distress, and increased ongoing opioid use versus compliant individuals. Discontinuation was initially related to drug-use severity; however, by 6 months, retention depended primarily upon cortisol abnormalities, which increased an individual's discontinuation risk by 7.7-fold. These findings support admission screening with the ASI/cortisol for drop out, and stress/drug-use indices for engagement that together may enable clinically-relevant early recognition and interventions for prevention of stress-induced relapse in opioid-dependent populations. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Concentration-dependent activation of dopamine receptors differentially modulates GABA release onto orexin neurons.

    Science.gov (United States)

    Linehan, Victoria; Trask, Robert B; Briggs, Chantalle; Rowe, Todd M; Hirasawa, Michiru

    2015-08-01

    Dopamine (DA) and orexin neurons play important roles in reward and food intake. There are anatomical and functional connections between these two cell groups: orexin peptides stimulate DA neurons in the ventral tegmental area and DA inhibits orexin neurons in the hypothalamus. However, the cellular mechanisms underlying the action of DA on orexin neurons remain incompletely understood. Therefore, the effect of DA on inhibitory transmission to orexin neurons was investigated in rat brain slices using the whole-cell patch-clamp technique. We found that DA modulated the frequency of spontaneous and miniature IPSCs (mIPSCs) in a concentration-dependent bidirectional manner. Low (1 μM) and high (100 μM) concentrations of DA decreased and increased IPSC frequency, respectively. These effects did not accompany a change in mIPSC amplitude and persisted in the presence of G-protein signaling inhibitor GDPβS in the pipette, suggesting that DA acts presynaptically. The decrease in mIPSC frequency was mediated by D2 receptors whereas the increase required co-activation of D1 and D2 receptors and subsequent activation of phospholipase C. In summary, our results suggest that DA has complex effects on GABAergic transmission to orexin neurons, involving cooperation of multiple receptor subtypes. The direction of dopaminergic influence on orexin neurons is dependent on the level of DA in the hypothalamus. At low levels DA disinhibits orexin neurons whereas at high levels it facilitates GABA release, which may act as negative feedback to curb the excitatory orexinergic output to DA neurons. These mechanisms may have implications for consummatory and motivated behaviours. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  8. Particle size- and concentration-dependent separation of magnetic nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Witte, Kerstin, E-mail: witte@micromod.de [University of Rostock, Institute of Physics, Albert-Einstein-Str. 23, 18059 Rostock (Germany); Micromod Partikeltechnologie GmbH, Friedrich-Barnewitz-Str. 4, 18119 Rostock (Germany); Müller, Knut; Grüttner, Cordula; Westphal, Fritz [Micromod Partikeltechnologie GmbH, Friedrich-Barnewitz-Str. 4, 18119 Rostock (Germany); Johansson, Christer [Acreo Swedish ICT AB, 40014 Göteborg (Sweden)

    2017-04-01

    Small magnetic nanoparticles with a narrow size distribution are of great interest for several biomedical applications. When the size of the particles decreases, the magnetic moment of the particles decreases. This leads to a significant increase in the separation time by several orders of magnitude. Therefore, in the present study the separation processes of bionized nanoferrites (BNF) with different sizes and concentrations were investigated with the commercial Sepmag Q system. It was found that an increasing initial particle concentration leads to a reduction of the separation time for large nanoparticles due to the higher probability of building chains. Small nanoparticles showed exactly the opposite behavior with rising particle concentration up to 0.1 mg(Fe)/ml. For higher iron concentrations the separation time remains constant and the measured Z-average decreases in the supernatant at same time intervals. At half separation time a high yield with decreasing hydrodynamic diameter of particles can be obtained using higher initial particle concentrations. - Highlights: • Size dependent separation processes of multicore nanoparticles. • Concentration dependent separation processes of multicore nanoparticles. • Increasing separation time with rising concentrations for small particles. • Large particles show typical cooperative magnetophoresis behavior.

  9. ATG-Fresenius inhibits blood circulating cell proliferation in a dose-dependent manner: an experimental study.

    Science.gov (United States)

    Werner, I; Seitz-Merwald, I; Kiessling, A H; Kur, F; Beiras-Fernandez, A

    2014-11-01

    Antithymocyte globulin (ATG)-Fresenius (Neovii-Biotech, Graefelfing, Germany), a highly purified rabbit polyclonal antihuman T-lymphocyte immunoglobulin resulting from immunization of rabbits with the Jurkat T-lymphoblast cell line, is currently used for the prevention of acute rejection in patients receiving solid organ transplants. Our aim was to investigate the in vitro activity of ATG-Fresenius regarding the proliferation of peripheral blood mononuclear cells (PBMCs), an important mechanism of rejection after solid organ transplantation. PBMCs were isolated from 6 healthy donors. Proliferation was assayed using [(3)H] thymidine incorporation. For analysis of mitogen-stimulated proliferation, the PBMCs were incubated at 37°C with various concentrations of ATG-Fresenius in the absence/presence of 40 μg/mL phytohemagglutinin. For analysis of the mixed lymphocyte reaction, PBMCs were incubated at 37°C with various concentrations of ATG-Fresenius for 3 days. On day 3, PBMCs (stimulator cells) from allogeneic donors were incubated with 25 μg/mL mitomycin C. The responder cells (preincubated with ATG-Fresenius) were then cultured at 37°C with the stimulator cells for 6 days. Groups were compared using ANOVA and the Tukey-Kramer multiple comparison test. Preincubation of PBMCs with ATG results in concentration-dependent inhibition of phytohemagglutinin-stimulated proliferation. The effect was more pronounced after 2 and 3 days of treatment with ATG compared with 1 day. There was a concentration-dependent decrease in the mixed lymphocyte reaction-induced proliferation (up to 80%) at ATG-Fresenius concentrations as low as 0.05 to 0.5 μg/mL. No further effect on proliferation at ATG-Fresenius concentrations of 0.5 to 50 μg/mL was seen, and higher concentrations (>100 μg/mL) totally inhibited proliferation. Our in vitro results provide more evidence of the beneficial effect of ATGs in the early phase of solid organ transplantation, by reducing effector cell

  10. Intermittent Hypoxia Disrupts Glucose Homeostasis in Liver Cells in an Insulin-Dependent and Independent Manner

    Directory of Open Access Journals (Sweden)

    Chen Juan Gu

    2018-05-01

    Full Text Available Background/Aims: Obstructive sleep apnea is associated with diabetes and insulin resistance, but the underlying mechanisms remain unclear. The purpose of the current study was to determine the molecular effects of intermittent hypoxia (IH on hepatic insulin signaling and glucose homeostasis, and whether c-Jun NH2-terminal-kinase (JNK contributed to metabolic responses to IH in liver cells. Methods: The human HepG2 cells and rat FAO cells were exposed to 10, 30, 120, 240 or 360 cycles of IH (1% O2 for 60 s followed by 21% O2 for 60s, 7.5 cycles per hour or normoxia as a control. In a subgroup, we exposed cells to 360 cycles of IH with the JNK inhibitor SP600125. After IH exposure, cell glycogen content and glucose output were measured using colorimetric assay kits. Canonical insulin signaling and gluconeogenic genes were measured by western blot and quantitative polymerase chain reaction. Results: IH decreased insulin-stimulated protein kinase B (AKT/glycogen synthase kinase-3β (GSK-3β phosphorylation in a time-dependent manner, while inhibiting forkhead box protein O1 (FOXO1 expression and phosphoenolpyruvate carboxykinase (PEPCK transcription independent of insulin signaling. JNK inhibitor SP600125 partially restored AKT/ GSK-3β phosphorylation and glycogen synthesis, but did not affect other IH-induced glucose metabolic changes. Conclusion: IH in vitro impaired insulin signal transduction in liver cells as assessed by inhibited AKT/GSK-3β phosphorylation via JNK activation. IH inhibited FOXO1 and gluconeogenesis in an insulin-independent manner.

  11. The aPKC-CBP Pathway Regulates Adult Hippocampal Neurogenesis in an Age-Dependent Manner

    Directory of Open Access Journals (Sweden)

    Ayden Gouveia

    2016-10-01

    Full Text Available While epigenetic modifications have emerged as attractive substrates to integrate environmental changes into the determination of cell identity and function, specific signals that directly activate these epigenetic modifications remain unknown. Here, we examine the role of atypical protein kinase C (aPKC-mediated Ser436 phosphorylation of CBP, a histone acetyltransferase, in adult hippocampal neurogenesis and memory. Using a knockin mouse strain (CbpS436A in which the aPKC-CBP pathway is deficient, we observe impaired hippocampal neuronal differentiation, maturation, and memory and diminished binding of CBP to CREB in 6-month-old CbpS436A mice, but not at 3 months of age. Importantly, elevation of CREB activity rescues these deficits, and CREB activity is reduced whereas aPKC activity is increased in the murine hippocampus as they age from 3 to 6 months regardless of genotype. Thus, the aPKC-CBP pathway is a homeostatic compensatory mechanism that modulates hippocampal neurogenesis and memory in an age-dependent manner in response to reduced CREB activity.

  12. Bone mineral density-associated polymorphisms are associated with obesity-related traits in Korean adults in a sex-dependent manner.

    Directory of Open Access Journals (Sweden)

    Seongwon Cha

    Full Text Available Obesity and osteoporosis share common physiological factors, including the presence of atherosclerosis, a risk factor for cardiometabolic disease, as well as a common progenitor that differentiates into both adipocytes and osteoblasts. Among the 23 polymorphisms associated with bone mineral density (BMD in recent genome-wide association studies (GWASs, an Osterix polymorphism has been identified and associated with childhood obesity in girls. Therefore, we focused on elucidating polymorphisms associated with adulthood obesity in a sex-dependent manner among the previously published BMD-associated polymorphisms from GWASs. We performed 2 screenings of 18 BMD-associated polymorphisms for obesity-related traits in 2,362 adults aged >20 years. We excluded 13 polymorphisms showing deviations from Hardy-Weinberg equilibrium or no association with obesity-related traits (body mass index, waist circumference (WC, and waist-to-hip ratio. Among 5 selected polymorphisms (rs9594738 of RANKL, rs17066364 of NUFIP1, rs7227401 of OSBPL1A, and rs1856057 and rs2982573 of ESR1 analyzed, 2 polymorphisms (rs9594738 and rs17066364 were associated with obesity-related traits. We found sex-dependent associations such that the 4 polymorphisms (excluding rs9594738 of RANKL were associated with abdominal traits such as WC and waist-to-hip ratio only in men. In addition, when the combined genetic risk score (GRS for WC increase was calculated with 4 SNPs (rs9594738, rs17066364, rs7227401, and rs1856057 exhibiting similar trends for both sexes, the magnitude of the GRS effect for the WC increase was larger in men than in women (effect size = 0.856 cm, P = 0.0000452 for men; effect size = 0.598 cm, P = 0.00228 for women. In summary, we found 4 polymorphisms, previously related to osteoporosis, to be associated to obesity-related traits in a sex-dependent manner in Korean adults, particularly in men.

  13. Help to perpetuate traditional gender roles: Benevolent sexism increases engagement in dependency-oriented cross-gender helping.

    Science.gov (United States)

    Shnabel, Nurit; Bar-Anan, Yoav; Kende, Anna; Bareket, Orly; Lazar, Yael

    2016-01-01

    Based on theorizing that helping relations may serve as a subtle mechanism to reinforce intergroup inequality, the present research (N = 1,315) examined the relation between benevolent sexism (i.e., a chivalrous yet subtly oppressive view of women) and helping. In cross-gender interactions, the endorsement of (Studies 1, 3, and 4) or exposure to (Study 2) benevolent sexism predicted (a) men's preference to provide women with dependency-oriented help (i.e., direct assistance) rather than tools for autonomous coping, and (b) women's preference to seek dependency-oriented help rather than tools for autonomous coping. Benevolent sexism did not predict men's and women's engagement in dependency-oriented helping relations in same-gender interactions. Studies 1 and 2 examined behavioral intentions in response to a series of hypothetical scenarios; Studies 3 and 4 examined actual behavior in tests of mathematical and logical ability, and pointed to assumed partner's expectations as a potential mediator. The converging evidence supports the hypothesis that benevolent sexism encourages engagement in cross-gender helping relations that perpetuate traditional gender roles. (c) 2016 APA, all rights reserved).

  14. Learning words during shared book reading: The role of extratextual talk designed to increase child engagement.

    Science.gov (United States)

    Blewitt, Pamela; Langan, Ryan

    2016-10-01

    Shared book reading (SBR) is a valuable context for word learning during early childhood, and adults' extratextual talk boosts the vocabulary building potential of SBR. We propose that the benefits of such talk depend largely on a reader's success in promoting children's active engagement (attention and interest) during SBR. When readers ask children questions about new words, especially if they respond to children in a prompt, contingent, and appropriate (positive) manner, this verbal responsiveness functions as an effective engagement strategy. We randomly assigned 3- and 4-year-olds to three reading conditions (low, moderate, and high) distinguished by the degree to which the reader used extratextual engagement strategies, including verbal responsiveness. Despite equal exposure to unfamiliar target words, children's performance improved on two measures of word learning across the three conditions, demonstrating the value of engagement strategies in extratextual talk. This study provides a strong experimental demonstration that adult verbal responsiveness directly benefits preschoolers' word learning. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Concentration dependent hydrogen diffusion in tungsten

    Energy Technology Data Exchange (ETDEWEB)

    Ahlgren, T., E-mail: tommy.ahlgren@helsinki.fi; Bukonte, L.

    2016-10-15

    The diffusion of hydrogen in tungsten is studied as a function of temperature, hydrogen concentration and pressure using Molecular Dynamics technique. A new analysis method to determine diffusion coefficients that accounts for the random oscillation of atoms around the equilibrium position is presented. The results indicate that the hydrogen migration barrier of 0.25 eV should be used instead of the presently recommended value of 0.39 eV. This conclusion is supported by both experiments and density functional theory calculations. Moreover, the migration volume at the saddle point for H in W is found to be positive: ΔV{sub m} ≈ 0.488 Å{sup 3}, leading to a decrease in the diffusivity at high pressures. At high H concentrations, a dramatic reduction in the diffusion coefficient is observed, due to site blocking and the repulsive H-H interaction. The results of this study indicates that high flux hydrogen irradiation leads to much higher H concentrations in tungsten than expected. - Highlights: • The recommended value of 0.39 eV for the H in W migration barrier should be changed to 0.25 eV. • The random oscillation of atoms around the equilibrium position can be dealt with in diffusion simulations. • Hydrogen diffusion in tungsten is highly concentration dependent.

  16. GTP depletion synergizes the anti-proliferative activity of chemotherapeutic agents in a cell type-dependent manner

    International Nuclear Information System (INIS)

    Lin, Tao; Meng, Lingjun; Tsai, Robert Y.L.

    2011-01-01

    Highlights: → Strong synergy between mycophenolic acid (MPA) and 5-FU in MDA-MB-231 cells. → Cell type-dependent synergy between MPA and anti-proliferative agents. → The synergy of MPA on 5-FU is recapitulated by RNA polymerase-I inhibition. → The synergy of MPA on 5-FU requires the expression of nucleostemin. -- Abstract: Mycophenolic acid (MPA) depletes intracellular GTP by blocking de novo guanine nucleotide synthesis. GTP is used ubiquitously for DNA/RNA synthesis and as a signaling molecule. Here, we made a surprising discovery that the anti-proliferative activity of MPA acts synergistically with specific chemotherapeutic agents in a cell type-dependent manner. In MDA-MB-231 cells, MPA shows an extremely potent synergy with 5-FU but not with doxorubicin or etoposide. The synergy between 5-FU and MPA works most effectively against the highly tumorigenic mammary tumor cells compared to the less tumorigenic ones, and does not work in the non-breast cancer cell types that we tested, with the exception of PC3 cells. On the contrary, MPA shows the highest synergy with paclitaxel but not with 5-FU in SCC-25 cells, derived from oral squamous cell carcinomas. Mechanistically, the synergistic effect of MPA on 5-FU in MDA-MB-231 cells can be recapitulated by inhibiting the RNA polymerase-I activity and requires the expression of nucleostemin. This work reveals that the synergy between MPA and anti-proliferative agents is determined by cell type-dependent factors.

  17. Argon inhalation attenuates retinal apoptosis after ischemia/reperfusion injury in a time- and dose-dependent manner in rats.

    Directory of Open Access Journals (Sweden)

    Felix Ulbrich

    Full Text Available Retinal ischemia and reperfusion injuries (IRI permanently affect neuronal tissue and function by apoptosis and inflammation due to the limited regenerative potential of neurons. Recently, evidence emerged that the noble gas Argon exerts protective properties, while lacking any detrimental or adverse effects. We hypothesized that Argon inhalation after IRI would exert antiapoptotic effects in the retina, thereby protecting retinal ganglion cells (RGC of the rat's eye.IRI was performed on the left eyes of rats (n = 8 with or without inhaled Argon postconditioning (25, 50 and 75 Vol% for 1 hour immediately or delayed after ischemia (i.e. 1.5 and 3 hours. Retinal tissue was harvested after 24 hours to analyze mRNA and protein expression of Bcl-2, Bax and Caspase-3, NF-κB. Densities of fluorogold-prelabeled RGCs were analyzed 7 days after injury in whole-mounts. Histological tissue samples were prepared for immunohistochemistry and blood was analyzed regarding systemic effects of Argon or IRI. Statistics were performed using One-Way ANOVA.IRI induced RGC loss was reduced by Argon 75 Vol% inhalation and was dose-dependently attenuated by lower concentrations, or by delayed Argon inhalation (1504±300 vs. 2761±257; p<0.001. Moreover, Argon inhibited Bax and Bcl-2 mRNA expression significantly (Bax: 1.64±0.30 vs. 0.78±0.29 and Bcl-2: 2.07±0.29 vs. 0.99±0.22; both p<0.01, as well as caspase-3 cleavage (1.91±0.46 vs. 1.05±0.36; p<0.001. Expression of NF-κB was attenuated significantly. Immunohistochemistry revealed an affection of Müller cells and astrocytes. In addition, IRI induced leukocytosis was reduced significantly after Argon inhalation at 75 Vol%.Immediate and delayed Argon postconditioning protects IRI induced apoptotic loss of RGC in a time- and dose-dependent manner, possibly mediated by the inhibition of NF-κB. Further studies need to evaluate Argon's possible role as a therapeutic option.

  18. ERβ1 inhibits the migration and invasion of breast cancer cells through upregulation of E-cadherin in a Id1-dependent manner

    International Nuclear Information System (INIS)

    Zhou, Yan; Ming, Jia; Xu, Yan; Zhang, Yi; Jiang, Jun

    2015-01-01

    Highlights: • Expression of ERβ1 was positively correlated with E-cadherin in breast cancer cell. • ERβ1 upregulates E-cadherin expression in breast cancer cell lines. • ERβ1 upregulates E-cadherin expression in a Id1-dependent manner. - Abstract: ERβ1 is a member of the nuclear receptor superfamily of ligand-regulated transcription factors. It plays an important role in regulating the progression of breast cancer. However, the mechanisms of ERβ1 in tumorigenesis, metastasis and prognosis are still not fully clear. In this study, we showed that the expression of ERβ1 was positively correlated with E-cadherin expression in breast cancer cell lines. In addition, we found that ERβ1 upregulates E-cadherin expression in breast cancer cell lines. Furthermore, we also found that ERβ1 inhibits the migration and invasion of breast cancer cells and upregulated E-cadherin expression in a Id1-dependent manner. Taken together, our study provides further understanding of the molecular mechanism of ERβ1 in tumor metastasis and suggests the feasibility of developing novel therapeutic approaches to target Id1 to inhibit breast cancer metastasis

  19. Neuron-astrocyte interaction enhance GABAergic synaptic transmission in a manner dependent on key metabolic enzymes.

    Directory of Open Access Journals (Sweden)

    Przemysław eKaczor

    2015-04-01

    Full Text Available GABA is the major inhibitory neurotransmitter in the adult brain and mechanisms of GABAergic inhibition have been intensely investigated in the past decades. Recent studies provided evidence for an important role of astrocytes in shaping GABAergic currents. One of the most obvious, but yet poorly understood, mechanisms of the cross-talk between GABAergic currents and astrocytes is metabolism including neurotransmitter homeostasis. In particular, how modulation of GABAergic currents by astrocytes depends on key enzymes involved in cellular metabolism remains largely unknown. To address this issue, we have considered two simple models of neuronal cultures: nominally astrocyte-free neuronal culture (NC and neuronal-astrocytic co-cultures (ANCC and miniature Inhibitory Postsynaptic Currents (mIPSCs were recorded in control conditions and in the presence of respective enzyme blockers. We report that enrichment of neuronal culture with astrocytes results in a marked increase in mIPSC frequency. This enhancement of GABAergic activity was accompanied by increased number of GAD65 and vGAT puncta, indicating that at least a part of the frequency enhancement was due to increased number of synaptic contacts. Inhibition of glutamine synthetase (with MSO strongly reduced mIPSC frequency in ANCC but had no effect in NC. Moreover, treatment of ANCC with inhibitor of glycogen phosphorylase (BAYU6751 or with selective inhibitor of astrocytic Krebs cycle,fluoroacetate, resulted in a marked reduction of mIPSC frequency in ANCC having no effect in NC. We conclude that GABAergic synaptic transmission strongly depends on neuron-astrocyte interaction in a manner dependent on key metabolic enzymes as well as on the Krebs cycle.

  20. Unusual concentration-dependent microscopic dynamics of dendrimers in aqueous solution

    International Nuclear Information System (INIS)

    Wong, Kaikin; Wu, Chin Ming; Lam, Hak Fai; Chathoth, Suresh M.

    2016-01-01

    Dendrimers are novel three-dimensional, hyperbranched globular nanopolymeric macromolecules. The nanoscopic size, narrow polydispersity index, excellent control over molecular structure, availability of multiple functional groups at the periphery, and cavities in the interior made them very attractive candidate for drug delivery. In this communication, we have studied the microscopic dynamics of tetra-acid and pentaerythritol glycidyl ether dendrimers dissolved in aqueous solution with different concentrations. The effects of concentration and temperature to their long-range diffusion process are investigated by dynamic light scattering. Experimental results show a huge variation in the translational diffusion coefficient for the two dendrimers samples. Besides, the dependence of diffusion coefficients on concentration is unusually different in these dendrimer samples. Although the diffusion process follows Arrhenius relation with the temperature in both systems, the activation energy for the diffusion process has a distinct concentration dependence.

  1. Unusual concentration-dependent microscopic dynamics of dendrimers in aqueous solution

    Science.gov (United States)

    Wong, Kaikin; Wu, Chin Ming; Lam, Hak Fai; Chathoth, Suresh M.

    2016-05-01

    Dendrimers are novel three-dimensional, hyperbranched globular nanopolymeric macromolecules. The nanoscopic size, narrow polydispersity index, excellent control over molecular structure, availability of multiple functional groups at the periphery, and cavities in the interior made them very attractive candidate for drug delivery. In this communication, we have studied the microscopic dynamics of tetra-acid and pentaerythritol glycidyl ether dendrimers dissolved in aqueous solution with different concentrations. The effects of concentration and temperature to their long-range diffusion process are investigated by dynamic light scattering. Experimental results show a huge variation in the translational diffusion coefficient for the two dendrimers samples. Besides, the dependence of diffusion coefficients on concentration is unusually different in these dendrimer samples. Although the diffusion process follows Arrhenius relation with the temperature in both systems, the activation energy for the diffusion process has a distinct concentration dependence.

  2. Unusual concentration-dependent microscopic dynamics of dendrimers in aqueous solution

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Kaikin; Wu, Chin Ming; Lam, Hak Fai; Chathoth, Suresh M., E-mail: smavilac@cityu.edu.hk [City University of Hong Kong, Department of Physics and Materials Science (Hong Kong, People’s Republic of China) (China)

    2016-05-15

    Dendrimers are novel three-dimensional, hyperbranched globular nanopolymeric macromolecules. The nanoscopic size, narrow polydispersity index, excellent control over molecular structure, availability of multiple functional groups at the periphery, and cavities in the interior made them very attractive candidate for drug delivery. In this communication, we have studied the microscopic dynamics of tetra-acid and pentaerythritol glycidyl ether dendrimers dissolved in aqueous solution with different concentrations. The effects of concentration and temperature to their long-range diffusion process are investigated by dynamic light scattering. Experimental results show a huge variation in the translational diffusion coefficient for the two dendrimers samples. Besides, the dependence of diffusion coefficients on concentration is unusually different in these dendrimer samples. Although the diffusion process follows Arrhenius relation with the temperature in both systems, the activation energy for the diffusion process has a distinct concentration dependence.

  3. Effect of nitrogen concentration on temperature dependent mechanical properties of vanadium

    International Nuclear Information System (INIS)

    Carlson, O.N.; Rehbein, D.K.

    1979-01-01

    The critical resolved shear stress and strain rate sensitivity of vanadium were determined for vanadium-nitrogen alloys over the temperature range of 77K to 400K for concentrations of 1 to 500 wt ppm nitrogen. The concentration dependence of the hardening rate agrees quite well with either the Fleischer or Labusch strengthening model but the combined temperature and concentration dependence follows more closely the form predicted by Ono and Sommer. The strain rate sensitivity exhibits a peak at 140K which decreases with increasing nitrogen content but above 250K there is a reversal in this effect. (orig.) [de

  4. The sea anemone Bunodosoma caissarum toxin BcIII modulates the sodium current kinetics of rat dorsal root ganglia neurons and is displaced in a voltage-dependent manner.

    Science.gov (United States)

    Salceda, Emilio; López, Omar; Zaharenko, André J; Garateix, Anoland; Soto, Enrique

    2010-03-01

    Sea anemone toxins bind to site 3 of the sodium channels, which is partially formed by the extracellular linker connecting S3 and S4 segments of domain IV, slowing down the inactivation process. In this work we have characterized the actions of BcIII, a sea anemone polypeptide toxin isolated from Bunodosoma caissarum, on neuronal sodium currents using the patch clamp technique. Neurons of the dorsal root ganglia of Wistar rats (P5-9) in primary culture were used for this study (n=65). The main effects of BcIII were a concentration-dependent increase in the sodium current inactivation time course (IC(50)=2.8 microM) as well as an increase in the current peak amplitude. BcIII did not modify the voltage at which 50% of the channels are activated or inactivated, nor the reversal potential of sodium current. BcIII shows a voltage-dependent action. A progressive acceleration of sodium current fast inactivation with longer conditioning pulses was observed, which was steeper as more depolarizing were the prepulses. The same was observed for other two anemone toxins (CgNa, from Condylactis gigantea and ATX-II, from Anemonia viridis). These results suggest that the binding affinity of sea anemone toxins may be reduced in a voltage-dependent manner, as has been described for alpha-scorpion toxins. (c) 2009 Elsevier Inc. All rights reserved.

  5. Dependency of soil activity concentration on soil -biota concentration ratio of radionuclides for earthworm

    Energy Technology Data Exchange (ETDEWEB)

    Keum, Dong Kwon; Kim, Byeong Ho; Jun, In; Lim, Kwang Muk; Choi, Yong Ho [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2012-05-15

    The transfer of radionuclides to wildlife (non-human biota) is normally quantified using an equilibrium concentration ratio (CR{sub eq}), defined as the radionuclide activity concentration in the whole organism (fresh weight) divided by that in the media (dry weight for soil). The present study describes the effect of soil radionuclide activity concentration on the transfer of {sup 137}Cs, {sup 85}Sr and {sup 65}Zn to a functionally important wildlife group, annelids, using a commonly studied experimental worm (E.andrei). Time-dependent whole body concentration ratios of {sup 137}Cs, {sup 85}Sr and {sup 65}Zn for the earthworm were experimentally measured for artificially contaminated soils with three different activity concentrations for each radionuclide which were considerably higher than normal background levels. Two parameters of a first order kinetic model, the equilibrium concentration ratio (CR{sub eq}) and the effective loss rate constant (k), were estimated by comparison of experimental CR results with the model prediction

  6. Peripubertal Caffeine Exposure Impairs Longitudinal Bone Growth in Immature Male Rats in a Dose- and Time-Dependent Manner.

    Science.gov (United States)

    Choi, Yun-Young; Choi, Yuri; Kim, Jisook; Choi, Hyeonhae; Shin, Jiwon; Roh, Jaesook

    2016-01-01

    This study investigated the dose- and time-dependent effects of caffeine consumption throughout puberty in peripubertal rats. A total of 85 male SD rats were randomly divided into four groups: control and caffeine-fed groups with 20, 60, or 120 mg/kg/day through oral gavage for 10, 20, 30, or 40 days. Caffeine decreased body weight gain and food consumption in a dose- and time-dependent manner, accompanied by a reduction in muscle and body fat. In addition, it caused a shortening and lightening of leg bones and spinal column. The total height of the growth plate decreased sharply at 40 days in the controls, but not in the caffeine-fed groups, and the height of hypertrophic zone in the caffeine-fed groups was lower than in the control. Caffeine increased the height of the secondary spongiosa, whereas parameters related to bone formation, such as bone area ratio, thickness and number of trabeculae, and bone perimeter, were significantly reduced. Furthermore, serum levels of IGF-1, estradiol, and testosterone were also reduced by the dose of caffeine exposure. Our results demonstrate that caffeine consumption can dose- and time-dependently inhibit longitudinal bone growth in immature male rats, possibly by blocking the physiologic changes in body composition and hormones relevant to bone growth.

  7. Temperature dependence of electron concentration in cadmium arsenide

    NARCIS (Netherlands)

    Gelten, M.J.; Blom, F.A.P.

    1979-01-01

    From measurements of the temperature dependence of the electron concentration in Cd 3 As 2 , we found values for the conduction-band parameters that are in good agreement with those recently reported by Aubin, Caron, and Jay-Gerin. However, in contrast with these authors we found no small overlap,

  8. Concentration-dependent effects of fullerenol on cultured hippocampal neuron viability

    Directory of Open Access Journals (Sweden)

    Zha YY

    2012-06-01

    Full Text Available Ying-ying Zha,1 Bo Yang,1 Ming-liang Tang,2 Qiu-chen Guo,1 Ju-tao Chen,1 Long-ping Wen,3 Ming Wang11CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, University of Science and Technology of China, Hefei, 2Suzhou Institute of NanoTech and NanoBionics, Chinese Academy of Sciences, Suzhou, 3Laboratory of Nano-biology, School of Life Sciences, University of Science and Technology of China, Hefei, People's Republic of ChinaBackground: Recent studies have shown that the biological actions and toxicity of the water-soluble compound, polyhydroxyfullerene (fullerenol, are related to the concentrations present at a particular site of action. This study investigated the effects of different concentrations of fullerenol on cultured rat hippocampal neurons.Methods and results: Fullerenol at low concentrations significantly enhanced hippocampal neuron viability as tested by MTT assay and Hoechst 33342/propidium iodide double stain detection. At high concentrations, fullerenol induced apoptosis confirmed by Comet assay and assessment of caspase proteins.Conclusion: These findings suggest that fullerenol promotes cell death and protects against cell damage, depending on the concentration present. The concentration-dependent effects of fullerenol were mainly due to its influence on the reduction-oxidation pathway.Keywords: fullerenol, nanomaterial, neurotoxicity, neuroprotection, hippocampal neuron

  9. Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration.

    Directory of Open Access Journals (Sweden)

    Donghee Park

    Full Text Available Sonophoresis can increase skin permeability to various drugs in transdermal drug delivery. Cavitation is recognized as the predominant mechanism of sonophoresis. Recently, a new logical approach to enhance the efficiency of transdermal drug delivery was tried. It is to utilize the engineered microbubble and its resonant frequency for increase of cavitation activity. Actively-induced cavitation with low-intensity ultrasound (less than ~1 MPa causes disordering of the lipid bilayers and the formation of aqueous channels by stable cavitation which indicates a continuous oscillation of bubbles. Furthermore, the mutual interactions of microbubble determined by concentration of added bubble are also thought to be an important factor for activity of stable cavitation, even in different characteristics of drug. In the present study, we addressed the dependence of ultrasound contrast agent concentration using two types of drug on the efficiency of transdermal drug delivery. Two types of experiment were designed to quantitatively evaluate the efficiency of transdermal drug delivery according to ultrasound contrast agent concentration. First, an experiment of optical clearing using a tissue optical clearing agent was designed to assess the efficiency of sonophoresis with ultrasound contrast agents. Second, a Franz diffusion cell with ferulic acid was used to quantitatively determine the amount of drug delivered to the skin sample by sonophoresis with ultrasound contrast agents. The maximum enhancement ratio of sonophoresis with a concentration of 1:1,000 was approximately 3.1 times greater than that in the ultrasound group without ultrasound contrast agent and approximately 7.5 times greater than that in the control group. These results support our hypothesis that sonophoresis becomes more effective in transdermal drug delivery due to the presence of engineered bubbles, and that the efficiency of transdermal drug delivery using sonophoresis with

  10. Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration.

    Science.gov (United States)

    Park, Donghee; Song, Gillsoo; Jo, Yongjun; Won, Jongho; Son, Taeyoon; Cha, Ohrum; Kim, Jinho; Jung, Byungjo; Park, Hyunjin; Kim, Chul-Woo; Seo, Jongbum

    2016-01-01

    Sonophoresis can increase skin permeability to various drugs in transdermal drug delivery. Cavitation is recognized as the predominant mechanism of sonophoresis. Recently, a new logical approach to enhance the efficiency of transdermal drug delivery was tried. It is to utilize the engineered microbubble and its resonant frequency for increase of cavitation activity. Actively-induced cavitation with low-intensity ultrasound (less than ~1 MPa) causes disordering of the lipid bilayers and the formation of aqueous channels by stable cavitation which indicates a continuous oscillation of bubbles. Furthermore, the mutual interactions of microbubble determined by concentration of added bubble are also thought to be an important factor for activity of stable cavitation, even in different characteristics of drug. In the present study, we addressed the dependence of ultrasound contrast agent concentration using two types of drug on the efficiency of transdermal drug delivery. Two types of experiment were designed to quantitatively evaluate the efficiency of transdermal drug delivery according to ultrasound contrast agent concentration. First, an experiment of optical clearing using a tissue optical clearing agent was designed to assess the efficiency of sonophoresis with ultrasound contrast agents. Second, a Franz diffusion cell with ferulic acid was used to quantitatively determine the amount of drug delivered to the skin sample by sonophoresis with ultrasound contrast agents. The maximum enhancement ratio of sonophoresis with a concentration of 1:1,000 was approximately 3.1 times greater than that in the ultrasound group without ultrasound contrast agent and approximately 7.5 times greater than that in the control group. These results support our hypothesis that sonophoresis becomes more effective in transdermal drug delivery due to the presence of engineered bubbles, and that the efficiency of transdermal drug delivery using sonophoresis with microbubbles depends on the

  11. Going “old school”: From bedside manner to deskside manner

    Directory of Open Access Journals (Sweden)

    David Fleischman

    2015-08-01

    Full Text Available Interaction between tertiary educators and students, we contend, improves trust and betters student responses to emotional distress while at university. Therefore, we introduce the “Deskside Manner Framework” as an emerging practice in the tertiary teaching and learning context to aid student transition success. Based on concepts and practice that originated primarily in the medical profession and later in other high credence professional contexts, the deskside manner framework includes: show respect, critical listening, the four Bs and follow up. Deskside manner is transferrable and we aim to facilitate it through workshops and by developing a digital repository of educator-student interaction stories.  

  12. Apolipoprotein A-IV constrains HPA and behavioral stress responsivity in a strain-dependent manner.

    Science.gov (United States)

    Packard, Amy E B; Zhang, Jintao; Myers, Brent; Ko, Chih-Wei; Wang, Fei; Tso, Patrick; Ulrich-Lai, Yvonne M

    2017-12-01

    There is a critical gap in our knowledge of the mechanisms that govern interactions between daily life experiences (e.g., stress) and metabolic diseases, despite evidence that stress can have profound effects on cardiometabolic health. Apolipoprotein A-IV (apoA-IV) is a protein found in chylomicrons (lipoprotein particles that transport lipids throughout the body) where it participates in lipid handling and the regulation of peripheral metabolism. Moreover, apoA-IV is expressed in brain regions that regulate energy balance including the arcuate nucleus. Given that both peripheral and central metabolic processes are important modulators of hypothalamic-pituitary-adrenocortical (HPA) axis activity, the present work tests the hypothesis that apoA-IV activity affects stress responses. As emerging data suggests that apoA-IV actions can vary with background strain, we also explore the strain-dependence of apoA-IV stress regulation. These studies assess HPA axis, metabolic (hyperglycemia), and anxiety-related behavioral responses to psychogenic stress in control (wildtype) and apoA-IV-deficient (KO) mice on either the C57Bl/6J (C57) or 129×1/SvJ (129) background strain. The results indicate that apoA-IV KO increases post-stress corticosterone and anxiety-related behavior specifically in the 129 strain, and increases stress-induced hyperglycemia exclusively in the C57 strain. These data support the hypothesis that apoA-IV is a novel factor that limits stress reactivity in a manner that depends on genetic background. An improved understanding of the complex relationship among lipid homeostasis, stress sensitivity, and genetics is needed to optimize the development of personalized treatments for stress- and metabolism-related diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Market integration and market concentration in horizontally differentiated industries

    OpenAIRE

    Eckel, Carsten

    2001-01-01

    This paper derives the impact of market integration on equilibrium firm size and market concentration in horizontally differentiated industries. We show that market concentration (measured by the number of firms) can rise as a consequence of market integration if firms engage in R&D competition. We also demonstrate that whether concentration occurs or not depends on the R&D production function and on consumer preferences. This result implies that the welfare effects of market integration are ...

  14. Analytical description of concentration dependence of surface tension in multicomponent systems

    Energy Technology Data Exchange (ETDEWEB)

    Dadashev, R; Kutuev, R [Complex Science Research Institute of the Science Academy of the Chechen Republic, 21 Staropromisl. shosse, Grozny 364096 (Russian Federation); Elimkhanov, D [Science Academy of the Chechen Republic (Russian Federation)], E-mail: edzhabrail@mail.ru

    2008-02-15

    From the basic fundamental thermodynamic expressions the equation of isotherms of the surface tension of a ternary system is received. Various assumptions concerning the concentration dependence of molar areas are usually made when the equation is derived. The dependence of the molar areas is calculated as an additive function of the structure of a volumetric phase or the structure of a surface layer. To define the concentration dependence of the molar areas we used a stricter thermodynamic expression offered by Butler. In the received equation the dependence of molar areas on the structure of the solution is taken into account. Therefore, the equation can be applied for the calculation of surface tension over a wide concentration range of the components. Unlike the known expressions, the equation includes the surface tension properties of lateral binary systems, which makes the accuracy of the calculated values considerably higher. Thus, among the advantages of the offered equation we can point out the mathematical simplicity of the received equation and the fact that the equation includes physical parameters the experimental definition of which does not present any special difficulties.

  15. Determination of the concentration dependent diffusion coefficient of nitrogen in expanded austenite

    DEFF Research Database (Denmark)

    Christiansen, Thomas; Somers, Marcel A. J.

    2008-01-01

    The concentration dependent diffusion coefficient of nitrogen in expanded austenite was determined from of the rate of retracting nitrogen from thin initially N-saturated coupons. Nitrogen saturated homogeneous foils of expanded austenite were obtained by nitriding AISI 304 and AISI 316 in pure...... in the composition range where nitrogen can be extracted by hydrogen gas at the diffusion temperature. Numerical simulation of the denitriding experiments shows that the thus determined concentration dependent diffusion coefficients are an accurate approximation of the actual diffusivity of nitrogen in expanded...... ammonia at 693 K and 718 K. Denitriding experiments were performed by equilibrating the foils with a successively lower nitrogen activity, as imposed by a gas mixture of ammonia and hydrogen. The concentration dependent diffusion coefficient of nitrogen in expanded austenite was approximated...

  16. Prostasin-dependent activation of epithelial Na+ channels by low plasmin concentrations

    DEFF Research Database (Denmark)

    Svenningsen, Per; Uhrenholt, Torben R; Palarasah, Yaseelan

    2009-01-01

    by which plasmin stimulates ENaC activity. Cy3-labeled plasmin was found to bind to the surface of the mouse cortical collecting duct cell line, M-1. Binding depended on a glycosylphosphatidylinositol (GPI)-anchored protein. Biotin-label transfer showed that plasmin interacted with the GPI-anchored protein...... plasmin-stimulated ENaC current in monolayers of M-1 cells at low plasmin concentration (1-4 microg/ml). At a high plasmin concentration of 30 microg/ml, there was no difference between cell layers treated with or without PI-PLC. Knockdown of prostasin attenuated binding of plasmin to M1 cells and blocked...... labeling of M-1 cells. Pretreatment with plasmin abolished labeling of M-1 cells in a prostasin-dependent way. We conclude that, at low concentrations, plasmin interacts with GPI-anchored prostasin, which leads to cleavage of the gamma-subunit and activation of ENaC, while at higher concentrations, plasmin...

  17. Why do patients engage in medical tourism?

    NARCIS (Netherlands)

    Runnels, V.; Carrera, Percivil Melendez

    2012-01-01

    Medical tourism is commonly perceived and popularly depicted as an economic issue, both at the system and individual levels. The decision to engage in medical tourism, however, is more complex, driven by patients¿ unmet need, the nature of services sought and the manner by which treatment is

  18. Moringa oleifera's Nutritious Aqueous Leaf Extract Has Anticancerous Effects by Compromising Mitochondrial Viability in an ROS-Dependent Manner.

    Science.gov (United States)

    Madi, Niveen; Dany, Mohammed; Abdoun, Salah; Usta, Julnar

    2016-01-01

    Moringa oleifera (MO) is an important dietary component for many populations in West Africa and the Indian subcontinent. In addition to its highly nutritious value, almost all parts of this plant have been widely used in folk medicine in curing infectious, cardiovascular, gastrointestinal, hepatic, and other diseases. Evidence-based research supported its versatile medicinal properties; however, more rigorous research is required to establish it in cancer therapy. As such, in this study we aim to investigate the in vitro anticancerous effect of Moringa oleifera's aqueous leaf extract. Moringa extract was prepared by soaking pulverized leaves in hot water mimicking the people's mode of the leaf drink preparation. Several assays were used to study the effect of different percentage concentrations of the extract on viability of A549 cells; levels of adenosine triphosphate (ATP), reactive oxygen species (ROS), and glutathione (GSH) generated; as well as percentage of lactate dehydrogenase (LDH) released at different time points. In addition to mitochondrial membrane potential, apoptotic events were assessed using western blotting for apoptotic markers and immunoflourescent flourescent labeled inhibitor of caspases (FLICA) assay. MO extract treatment resulted in a significant decrease in mitochondrial membrane potential (1 hour) and ATP levels (3 hours), followed by an increase in (6 hours) ROS, caspase activation, proapoptotic proteins expression (p53, SMAC/Diablo, AIF), and PARP-1 cleavage. This eventually resulted in decreased GSH levels and a decrease in viability. The cytotoxic effect was prevented upon pretreatment with antioxidant N-acetyl-cysteine. MO decreased as well the viability of HepG2, CaCo2, Jurkat, and HEK293 cells. Our findings identify a plant extract with an anticancerous effect on cancer cell lines. MO extract exerts its cytotoxic effect in A549 cancer cells by affecting mitochondrial viability and inducing apoptosis in an ROS-dependent manner.

  19. Iron oxide magnetic nanoparticles combined with actein suppress non-small-cell lung cancer growth in a p53-dependent manner

    Directory of Open Access Journals (Sweden)

    Wang MS

    2017-10-01

    Full Text Available Ming-Shan Wang,1 Liang Chen,2 Ya-Qiong Xiong,2 Jing Xu,2 Ji-Peng Wang,2 Zi-Li Meng2 1Department of Oncology, Huaiyin Hospital of Huai’an City, Huai’an, China; 2Department of Respiration, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China Abstract: Actein (AT is a triterpene glycoside isolated from the rhizomes of Cimicifuga foetida that has been investigated for its antitumor effects. AT treatment leads to apoptosis in various cell types, including breast cancer cells, by regulating different signaling pathways. Iron oxide (Fe3O4 magnetic nanoparticles (MNPs are nanomaterials with biocompatible activity and low toxicity. In the present study, the possible benefits of AT in combination with MNPs on non-small-cell lung cancer (NSCLC were explored in in vitro and in vivo studies. AT-MNP treatment contributed to apoptosis in NSCLC cells, as evidenced by activation of the caspase 3-signaling pathway, which was accompanied by downregulation of the antiapoptotic proteins Bcl2 and BclXL, and upregulation of the proapoptotic signals Bax and Bad. The death receptors of TRAIL were also elevated following AT-MNP treatment in a p53-dependent manner. Furthermore, a mouse xenograft model in vivo revealed that AT-MNP treatment exhibited no toxicity and suppressed NSCLC growth compared to either AT or MNP monotherapies. In conclusion, this study suggests a novel therapy to induce apoptosis in suppressing NSCLC growth in a p53-dependent manner by combining AT with Fe3O4 MNPs. Keywords: actein, Fe3O4 magnetic nanoparticles, NSCLC, apoptosis, p53

  20. Glymphatic clearance controls state-dependent changes in brain lactate concentration

    DEFF Research Database (Denmark)

    Lundgaard, Iben; Lu, Minh Lon; Yang, Ezra

    2017-01-01

    Brain lactate concentration is higher during wakefulness than in sleep. However, it is unknown why arousal is linked to an increase in brain lactate and why lactate declines within minutes of sleep. Here, we show that the glymphatic system is responsible for state-dependent changes in brain lacta......-lymphatic clearance. This analysis provides fundamental new insight into brain energy metabolism by demonstrating that glucose that is not fully oxidized can be exported as lactate via glymphatic-lymphatic fluid transport.......Brain lactate concentration is higher during wakefulness than in sleep. However, it is unknown why arousal is linked to an increase in brain lactate and why lactate declines within minutes of sleep. Here, we show that the glymphatic system is responsible for state-dependent changes in brain lactate...... concentration. Suppression of glymphatic function via acetazolamide treatment, cisterna magna puncture, aquaporin 4 deletion, or changes in body position reduced the decline in brain lactate normally observed when awake mice transition into sleep or anesthesia. Concurrently, the same manipulations diminished...

  1. Polyaspartic Acid Concentration Controls the Rate of Calcium Phosphate Nanorod Formation in High Concentration Systems

    Energy Technology Data Exchange (ETDEWEB)

    Krogstad, Daniel V. [Biosystems and; Wang, Dongbo [Biosystems and; Lin-Gibson, Sheng [Biosystems and

    2017-08-31

    Polyelectrolytes are known to greatly affect calcium phosphate (CaP) mineralization. The reaction kinetics as well as the CaP phase, morphology and aggregation state depend on the relative concentrations of the polyelectrolyte and the inorganic ions in a complex, nonlinear manner. This study examines the structural evolution and kinetics of polyaspartic acid (pAsp) directed CaP mineralization at high concentrations of polyelectrolytes, calcium, and total phosphate (19–30 mg/mL pAsp, 50–100 mM Ca2+, Ca/P = 2). Using a novel combination of characterization techniques including cryogenic transmission electron microscopy (cryo-TEM), spectrophotometry, X-ray total scattering pair distribution function analysis, and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), it was determined that the CaP mineralization occurred over four transition steps. The steps include the formation of aggregates of pAsp stabilized CaP spherical nanoparticles (sNP), crystallization of sNP, oriented attachment of the sNP into nanorods, and further crystallization of the nanorods. The intermediate aggregate sizes and the reaction kinetics were found to be highly polymer concentration dependent while the sizes of the particles were not concentration dependent. This study demonstrates the complex role of pAsp in controlling the mechanism as well as the kinetics of CaP mineralization.

  2. Fluoxetine regulates mTOR signalling in a region-dependent manner in depression-like mice

    Science.gov (United States)

    Liu, Xiao-Long; Luo, Liu; Mu, Rong-Hao; Liu, Bin-Bin; Geng, Di; Liu, Qing; Yi, Li-Tao

    2015-01-01

    Previous studies have demonstrated that the mammalian target of rapamycin (mTOR) signaling pathway has an important role in ketamine-induced, rapid antidepressant effects despite the acute administration of fluoxetine not affecting mTOR phosphorylation in the brain. However, the effects of long-term fluoxetine treatment on mTOR modulation have not been assessed to date. In the present study, we examined whether fluoxetine, a type of commonly used antidepressant agent, alters mTOR signaling following chronic administration in different brain regions, including the frontal cortex, hippocampus, amygdala and hypothalamus. We also investigated whether fluoxetine enhanced synaptic protein levels in these regions via the activation of the mTOR signaling pathway and its downstream regulators, p70S6K and 4E-BP-1. The results indicated that chronic fluoxetine treatment attenuated the chronic, unpredictable, mild stress (CUMS)-induced mTOR phosphorylation reduction in the hippocampus and amygdala of mice but not in the frontal cortex or the hypothalamus. Moreover, the CUMS-decreased PSD-95 and synapsin I levels were reversed by fluoxetine, and these effects were blocked by rapamycin only in the hippocampus. In conclusion, our findings suggest that chronic treatment with fluoxetine can induce synaptic protein expression by activating the mTOR signaling pathway in a region-dependent manner and mainly in the hippocampus. PMID:26522512

  3. Metformin decreases lung cancer risk in diabetic patients in a dose-dependent manner.

    Science.gov (United States)

    Tsai, Ming-Ju; Yang, Chih-Jen; Kung, Ya-Ting; Sheu, Chau-Chyun; Shen, Yu-Ting; Chang, Pi-Yu; Huang, Ming-Shyan; Chiu, Herng-Chia

    2014-11-01

    Higher risk of lung cancer has been noted in patients with type 2 diabetes mellitus (DM). Some observational studies have shown a reduced risk of lung cancer in DM patients taking metformin, but a dose-response relationship has never been reported. The aim of this study is to exam the association between the dose of metformin and the incidence of lung cancer in a Chinese population. The dataset used for this nationwide population-based study is a cohort of 1 million subjects randomly sampled from individuals enrolled in the Taiwan National Health Insurance system. We enrolled all subjects with newly diagnosed type 2 DM between 1997 and 2007. Subjects with a diagnosis of neoplasm before DM diagnosis, those using metformin before DM diagnosis, those with polycystic ovary syndrome, and those with a DM diagnosis before their 15 years of age were excluded. The demographic data and duration, cumulative dose and intensity of metformin use were compared between patients developing lung cancer and those without lung cancer. Totally, 47,356 subjects were identified. After adjusting for age, gender, and modified Charlson Comorbidity Index score, the utilization of metformin was an independent protecting factor, and the risk of developing lung cancer decreased progressively with either the higher cumulative dose or the higher intensity of metformin use. This study revealed that the use of metformin decreased the risk of lung cancer in a dose-dependent manner in patients with type 2 DM. The chemo-preventive effect of metformin deserves further study. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Concentration-dependent induction of reactive oxygen species, cell cycle arrest and apoptosis in human liver cells after nickel nanoparticles exposure.

    Science.gov (United States)

    Ahmad, Javed; Alhadlaq, Hisham A; Siddiqui, Maqsood A; Saquib, Quaiser; Al-Khedhairy, Abdulaziz A; Musarrat, Javed; Ahamed, Maqusood

    2015-02-01

    Due to advent of nanotechnology, nickel nanoparticles (Ni NPs) are increasingly recognized for their utility in various applications including catalysts, sensors and electronics. However, the environmental and human health effects of Ni NPs have not been fully investigated. In this study, we examined toxic effects of Ni NPs in human liver (HepG2) cells. Ni NPs were prepared and characterized by X-ray diffraction, transmission electron microscopy and dynamic light scattering. We observed that Ni NPs (size, ∼28 nm; concentration range, 25-100 μg/mL) induced cytotoxicity in HepG2 cells and degree of induction was concentration-dependent. Ni NPs were also found to induce oxidative stress in dose-dependent manner evident by induction of reactive oxygen species and depletion of glutathione. Cell cycle analysis of cells treated with Ni NPs exhibited significant increase of apoptotic cell population in subG1 phase. Ni NPs also induced caspase-3 enzyme activity and apoptotic DNA fragmentation. Upregulation of cell cycle checkpoint gene p53 and bax/bcl-2 ratio with a concomitant loss in mitochondrial membrane potential suggested that Ni NPs induced apoptosis in HepG2 cells was mediated through mitochondrial pathway. This study warrants that applications of Ni NPs should be carefully assessed as to their toxicity to human health. © 2013 Wiley Periodicals, Inc.

  5. MiR-132 regulates osteogenic differentiation via downregulating Sirtuin1 in a peroxisome proliferator-activated receptor β/δ–dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Gong, Kai; Qu, Bo; Liao, Dongfa; Liu, Da; Wang, Cairu; Zhou, Jingsong; Pan, Xianming, E-mail: xianmingpanxj@163.com

    2016-09-09

    MicroRNAs (miRNAs) play significant roles in multiple diseases by regulating the expression of their target genes. Type 2 diabetes mellitus (T2DM) is a chronic endocrine and metabolic disease with complex mechanisms. T2DM can result in diabetic osteoporosis (DO), which is characterized by bone loss, decreased bone mineral density and increased bone fractures. The promotion of osteogenic differentiation of osteoblasts is an effective way to treat osteoporosis. In the present study, high glucose (HG) and free fatty acids (FFA) were employed to mimic T2DM in MC3T3-E1 cells. To induce osteogenic differentiation, MC3T3-E1 cells were cultured in osteogenic medium. The results showed that osteogenic differentiation was significantly suppressed by HG and FFA. We found that miR-132 expression was significantly upregulated and much higher in HG-FFA–induced cells than other selected miRNAs, indicating that miR-132 might play an important role in DO. Furthermore, overexpression of miR-132 markedly inhibited the expression of key markers of osteogenic differentiation and alkaline phosphatase (ALP) activity. Reciprocally, inhibition of miR-132 restored osteogenic differentiation, even under treatment with HG-FFA. We also showed that Sirtuin 1 (Sirt1) was one of the target genes of miR-132, whose expression was controlled by miR-132. Ectopic expression of Sirt1 reversed the decrease in osteogenic differentiation caused by miR-132 and HG-FFA. These results demonstrated the direct role of miR-132 in suppressing osteogenic differentiation through downregulating Sirt1. Moreover, we demonstrated that peroxisome proliferator-activated receptor β/δ (PPARβ/δ) was a downstream molecule of Sirt1, and its knockout by PPARβ/δ siRNA significantly abolished the promotive effects of Sirt1 on osteogenic differentiation, indicating that Sirt1 functioned in a PPARβ/δ–dependent manner. Taken together, we provide crucial evidence that miR-132 plays a key role in regulating osteogenic

  6. MiR-132 regulates osteogenic differentiation via downregulating Sirtuin1 in a peroxisome proliferator-activated receptor β/δ–dependent manner

    International Nuclear Information System (INIS)

    Gong, Kai; Qu, Bo; Liao, Dongfa; Liu, Da; Wang, Cairu; Zhou, Jingsong; Pan, Xianming

    2016-01-01

    MicroRNAs (miRNAs) play significant roles in multiple diseases by regulating the expression of their target genes. Type 2 diabetes mellitus (T2DM) is a chronic endocrine and metabolic disease with complex mechanisms. T2DM can result in diabetic osteoporosis (DO), which is characterized by bone loss, decreased bone mineral density and increased bone fractures. The promotion of osteogenic differentiation of osteoblasts is an effective way to treat osteoporosis. In the present study, high glucose (HG) and free fatty acids (FFA) were employed to mimic T2DM in MC3T3-E1 cells. To induce osteogenic differentiation, MC3T3-E1 cells were cultured in osteogenic medium. The results showed that osteogenic differentiation was significantly suppressed by HG and FFA. We found that miR-132 expression was significantly upregulated and much higher in HG-FFA–induced cells than other selected miRNAs, indicating that miR-132 might play an important role in DO. Furthermore, overexpression of miR-132 markedly inhibited the expression of key markers of osteogenic differentiation and alkaline phosphatase (ALP) activity. Reciprocally, inhibition of miR-132 restored osteogenic differentiation, even under treatment with HG-FFA. We also showed that Sirtuin 1 (Sirt1) was one of the target genes of miR-132, whose expression was controlled by miR-132. Ectopic expression of Sirt1 reversed the decrease in osteogenic differentiation caused by miR-132 and HG-FFA. These results demonstrated the direct role of miR-132 in suppressing osteogenic differentiation through downregulating Sirt1. Moreover, we demonstrated that peroxisome proliferator-activated receptor β/δ (PPARβ/δ) was a downstream molecule of Sirt1, and its knockout by PPARβ/δ siRNA significantly abolished the promotive effects of Sirt1 on osteogenic differentiation, indicating that Sirt1 functioned in a PPARβ/δ–dependent manner. Taken together, we provide crucial evidence that miR-132 plays a key role in regulating osteogenic

  7. TiO2 nanoparticles disrupt cell adhesion and the architecture of cytoskeletal networks of human osteoblast-like cells in a size dependent manner.

    Science.gov (United States)

    Ibrahim, Mohamed; Schoelermann, Julia; Mustafa, Kamal; Cimpan, Mihaela R

    2018-04-30

    Human exposure to titanium dioxide nanoparticles (nano-TiO 2 ) is increasing. An internal source of nano-TiO 2 is represented by titanium-based orthopedic and dental implants can release nanoparticles (NPs) upon abrasion. Little is known about how the size of NPs influences their interaction with cytoskeletal protein networks and the functional/homeostatic consequences that might follow at the implant-bone interface with regard to osteoblasts. We investigated the effects of size of anatase nano-TiO 2 on SaOS-2 human osteoblast-like cells exposed to clinically relevant concentrations (0.05, 0.5, 5 mg/L) of 5 and 40 nm spherical nano-TiO 2 . Cell viability and proliferation, adhesion, spread and migration were assessed, as well as the orientation of actin and microtubule cytoskeletal networks. The phosphorylation of focal adhesion kinase (p-FAK Y397 ) and the expression of vinculin in response to nano-TiO 2 were also assessed. Treatment with nano-TiO 2 disrupted the actin and microtubule cytoskeletal networks leading to morphological modifications of SaOS-2 cells. The phosphorylation of p-FAK Y397 and the expression of vinculin were also modified depending on the particle size, which affected cell adhesion. Consequently, the cell migration was significantly impaired in the 5 nm-exposed cells compared to unexposed cells. The present work shows that the orientation of cytoskeletal networks and the focal adhesion proteins and subsequently the adhesion, spread and migration of SaOS-2 cells were affected by the selected nano-TiO 2 in a size dependent manner. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  8. Dosis Facit Sanitatem—Concentration-Dependent Effects of Resveratrol on Mitochondria

    Directory of Open Access Journals (Sweden)

    Corina T. Madreiter-Sokolowski

    2017-10-01

    Full Text Available The naturally occurring polyphenol, resveratrol (RSV, is known for a broad range of actions. These include a positive impact on lifespan and health, but also pro-apoptotic anti-cancer properties. Interestingly, cell culture experiments have revealed a strong impact of RSV on mitochondrial function. The compound was demonstrated to affect mitochondrial respiration, structure and mass of mitochondria as well as mitochondrial membrane potential and, ultimately, mitochondria-associated cell death pathways. Notably, the mitochondrial effects of RSV show a very strict and remarkable concentration dependency: At low concentrations, RSV (<50 μM fosters cellular antioxidant defense mechanisms, activates AMP-activated protein kinase (AMPK- and sirtuin 1 (SIRT1-linked pathways and enhances mitochondrial network formation. These mechanisms crucially contribute to the cytoprotective effects of RSV against toxins and disease-related damage, in vitro and in vivo. However, at higher concentrations, RSV (>50 μM triggers changes in (sub-cellular Ca2+ homeostasis, disruption of mitochondrial membrane potential and activation of caspases selectively yielding apoptotic cancer cell death, in vitro and in vivo. In this review, we discuss the promising therapeutic potential of RSV, which is most probably related to the compound’s concentration-dependent manipulation of mitochondrial function and structure.

  9. RELEVANCE OF RELIGIOUS LEADER ENGAGEMENT FOR THE AIR FORCE CHAPLAIN CORPS

    Science.gov (United States)

    2015-12-01

    organizations. They are ordained religious leaders who have been set them aside to do sacred works. Furthermore, as Navy Chaplain George Adams writes...AU/ACSC/CHAE, C/AY16 AIR COMMAND AND STAFF COLLEGE AIR UNIVERSITY RELEVANCE OF RELIGIOUS LEADER ENGAGEMENT FOR THE...agent of Religious Leader Engagement on deployments in an informal manner. As the nature of warfare continues to evolve toward a non-traditional

  10. A time-dependent degeneration manner of condyle in rat CFA-induced inflamed TMJ.

    Science.gov (United States)

    Xu, Liqin; Guo, Huilin; Li, Cheng; Xu, Jie; Fang, Wei; Long, Xing

    2016-01-01

    Temporomandibular joint (TMJ) inflammation is a potential risk factor of osteoarthritis (OA) but the detailed degenerative changes in the inflamed TMJ remain unclear. In this study, we evaluated the changes of condylar cartilage and subchondral bone in rat inflamed TMJ induced by Freund's complete adjuvant (CFA). Articular cavity was injected with CFA and the TMJ samples were collected 1, 2, 3, and 4-week post-injection. Hematoxylin & Eosin (H&E) staining, toluidine blue (TB) staining, Safranin O (S.O) staining, Masson trichrome staining and micro-CT were used to assess TMJ degeneration during inflammation. Osteoclast and osteoblast activities were analyzed by tartrate-resistant acid phosphatase (TRAP) staining and osteocalcin (OCN) immunohistochemistry staining respectively. The expression of receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) in condylar cartilage and subchondral bone was also evaluated through immunohistochemistry and RANKL/OPG ratio was evaluated. Reduced cartilage thickness, decreased number of chondrocytes, and down-regulated proteoglycan expression were observed in the condylar cartilage in the inflamed TMJ. Enhanced osteoclast activity, and expanded bone marrow cavity were reached the peak in the 2-week after CFA-injection. Meanwhile the RANKL/OPG ratio in the cartilage and subchondral bone also increased in the 2-week CFA-injection. Immature, unmineralized new bones with irregular trabecular bone structure, atypical condylar shape, up-regulated OCN expression, and decreased bone mineral density (BMD) were found in the inflamed TMJ. The time-dependent degeneration manner of TMJ cartilage and subchondral bone was found in CFA-induced arthritis rat model. The degeneration in the TMJ with inflammation might be a risk factor and should be concerned.

  11. The effect of points and audio on concentration, engagement, enjoyment, learning, motivation, and classroom dynamics using Kahoot!

    DEFF Research Database (Denmark)

    Wang, Alf Inge; Lieberoth, Andreas

    2016-01-01

    There are many examples on the use of game-based learning in and outside the classroom, along with evaluation of their effect in terms of engagement, learning, classroom dynamics, concentration, motivation and enjoyment. Most of the research in this area focuses on evaluations of the use of game-...... affected by use of audio. A total of 593 students participated in this experiment with a gender distribution of 44% female and 56 male students. Contribution: Factorial design method, lit review...

  12. Nuclear size is sensitive to NTF2 protein levels in a manner dependent on Ran binding

    Science.gov (United States)

    Vuković, Lidija D.; Jevtić, Predrag; Zhang, Zhaojie; Stohr, Bradley A.; Levy, Daniel L.

    2016-01-01

    ABSTRACT Altered nuclear size is associated with many cancers, and determining whether cancer-associated changes in nuclear size contribute to carcinogenesis necessitates an understanding of mechanisms of nuclear size regulation. Although nuclear import rates generally positively correlate with nuclear size, NTF2 levels negatively affect nuclear size, despite the role of NTF2 (also known as NUTF2) in nuclear recycling of the import factor Ran. We show that binding of Ran to NTF2 is required for NTF2 to inhibit nuclear expansion and import of large cargo molecules in Xenopus laevis egg and embryo extracts, consistent with our observation that NTF2 reduces the diameter of the nuclear pore complex (NPC) in a Ran-binding-dependent manner. Furthermore, we demonstrate that ectopic NTF2 expression in Xenopus embryos and mammalian tissue culture cells alters nuclear size. Finally, we show that increases in nuclear size during melanoma progression correlate with reduced NTF2 expression, and increasing NTF2 levels in melanoma cells is sufficient to reduce nuclear size. These results show a conserved capacity for NTF2 to impact on nuclear size, and we propose that NTF2 might be a new cancer biomarker. PMID:26823604

  13. Sorafenib modulates the radio sensitivity of hepatocellular carcinoma cells in vitro in a schedule-dependent manner

    Directory of Open Access Journals (Sweden)

    Li Qiaoqiao

    2012-10-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC has a high incidence and mortality. Radiotherapy and sorafenib have proven effective for HCC. Here, we investigated whether sorafenib modulated the response of HCC cells to irradiation in vitro, effect of timing of sorafenib, and the underlying mechanisms. Methods Cell viability of the HCC cell lines, SMMC-7721 and Bel-7402, was examined by the 3-(4,5-dimethylthiazol-2-yl-5(3-carboxymethoxyphenyl-2(4-sulfophenyl-2 H-terazolium (MTT assays. Clonogenic growth assays of SMMC-7721 and Bel-7402 were determined by colony formation assays. DNA damage was assessed by monitoring γ-HAX foci in irradiated cells with immunofluorescence microscopy, and cell cycle distribution changes were examined by flow cytometry. Effects of sorafenib (15 μM added 30 min prior to radiation (pre-irradiation sorafenib of SMMC-7721 and BEL-7402 or 24 h post-irradiation (post-irradiation sorafenib on irradiated SMMC-7721 and BEL-7402 cells were compared to those of radiation alone or no treatment. Results The effect of sorafenib was dependent on its time of addition in relationship to irradiation of cells. Pre-irradiation sorafenib did not significantly affect the viability of SMMC-7221 and BEL-7402 cells compared with irradiation treatment alone. In contrast, post-irradiation sorafenib increased the sensitivity of irradiated SMMC-7221 and BEL-7402 cells significantly in a time-dependent manner. Pre-irradiation sorafenib significantly increased the surviving fraction of SMMC-7221 and BEL-7402 cells in clonogenic assays whereas post-irradiation sorafenib significantly reduced the surviving fractions of SMMC-7221 and BEL-7402 cells. SMMC-7721 cells treated with sorafenib 30 min before irradiation had significantly fewer cells with γ-H2AX foci (23.8 ± 2.9% than SMMC-7721 cells receiving radiation alone (59.9 ± 2.4; P  Conclusions Sorafenib combined with irradiation exerted a schedule-dependent effect in

  14. Cisplatin-resistant lung cancer cell-derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100-5p-dependent manner.

    Science.gov (United States)

    Qin, Xiaobing; Yu, Shaorong; Zhou, Leilei; Shi, Meiqi; Hu, Yong; Xu, Xiaoyue; Shen, Bo; Liu, Siwen; Yan, Dali; Feng, Jifeng

    2017-01-01

    Exosomes derived from lung cancer cells confer cisplatin (DDP) resistance to other cancer cells. However, the underlying mechanism is still unknown. A549 resistance to DDP (A549/DDP) was established. Microarray was used to analyze microRNA (miRNA) expression profiles of A549 cells, A549/DDP cells, A549 exosomes, and A549/DDP exosomes. There was a strong correlation of miRNA profiles between exosomes and their maternal cells. A total of 11 miRNAs were significantly upregulated both in A549/DDP cells compared with A549 cells and in exosomes derived from A549/DDP cells in contrast to exosomes from A549 cells. A total of 31 downregulated miRNAs were also observed. miR-100-5p was the most prominent decreased miRNA in DDP-resistant exosomes compared with the corresponding sensitive ones. Downregulated miR-100-5p was proved to be involved in DDP resistance in A549 cells, and mammalian target of rapamycin (mTOR) expression was reverse regulated by miR-100-5p. Exosomes confer recipient cells' resistance to DDP in an exosomal miR-100-5p-dependent manner with mTOR as its potential target both in vitro and in vivo. Exosomes from DDP-resistant lung cancer cells A549 can alter other lung cancer cells' sensitivity to DDP in exosomal miR-100-5p-dependent manner. Our study provides new insights into the molecular mechanism of DDP resistance in lung cancer.

  15. UV-induced nuclear import of XPA is mediated by importin-α4 in an ATR-dependent manner.

    Directory of Open Access Journals (Sweden)

    Zhengke Li

    Full Text Available Xeroderma pigmentosum Group A (XPA is a crucial factor in mammalian nucleotide excision repair (NER and nuclear import of XPA from the cytoplasm for NER is regulated in cellular DNA damage responses in S-phase. In this study, experiments were carried out to determine the transport mechanisms that are responsible for the UV (ultraviolet-induced nuclear import of XPA. We found that, in addition to the nuclear localization signal (NLS of XPA, importin-α4 or/and importin-α7 are required for the XPA nuclear import. Further investigation indicated that, importin-α4 and importin-α7 directly interacted with XPA in cells. Interestingly, the binding of importin-α4 to XPA was dependent on UV-irradiation, while the binding of importin-α7 was not, suggesting a role for importin-α7 in nuclear translocation of XPA in the absence of DNA damage, perhaps with specificity to certain non-S-phases of the cell-cycle. Consistent with the previous report of a dependence of UV-induced XPA nuclear import on ataxia telangiectasia and Rad3-related protein (ATR in S-phase, knockdown of ATR reduced the amount of XPA interacting with importin-α4. In contrast, the GTPase XPA binding protein 1 (XAB1, previously proposed to be required for XPA nuclear import, showed no effect on the nuclear import of XPA in our siRNA knockdown analysis. In conclusion, our results suggest that upon DNA damage transport adaptor importin-α4 imports XPA into the nucleus in an ATR-dependent manner, while XAB1 has no role in this process. In addition, these findings reveal a potential new therapeutic target for the sensitization of cancer cells to chemotherapy.

  16. Synthesis and concentration dependent antibacterial activities of CuO nanoflakes

    Energy Technology Data Exchange (ETDEWEB)

    Pandiyarajan, T.; Udayabhaskar, R. [Department of Physics, National Institute of Technology, Tiruchirappalli 620 015 (India); Vignesh, S.; James, R. Arthur [Department of Marine Science, Bharathidasan University, Tiruchirappalli 620 024 (India); Karthikeyan, B., E-mail: balkarin@yahoo.com [Department of Physics, National Institute of Technology, Tiruchirappalli 620 015 (India)

    2013-05-01

    We report, synthesis and antibacterial activities of CuO nanoflakes. CuO nanoparticles are prepared at room temperature through sol–gel method. X-ray diffraction studies show the particles are monoclinic (crystalline) in nature. Scanning electron microscopy (SEM) images clearly show that the prepared particles are flake like in structure. Fourier transform infrared (FTIR) spectra exhibits three different bands that correspond to the A{sub u} and B{sub u} modes. Antibacterial studies were performed on Shigella flexneri, Staphylococcus aureus, Staphylococcus epidermidis, Salmonella typhimurium, Bacillus subtilis, Escherichia coli, Vibrio cholera, Pseudomonas aeruginosa and Aeromonas liquefaciens bacterial strains. Among these bacterial strains, S. flexneri and B. subtilis are most sensitive to copper oxide nanoparticles than the positive control (Penicillin G) and S. typhimurium strain shows the less sensitive. Results show that sensitivity is highly dependent on the concentrations of CuO nanoflakes. - Highlights: ► CuO nanoflakes are prepared through simple sol–gel method at room temperature. ► Bacterial strains are highly affected by CuO nanoflakes than the positive control. ► Zone of inhibition increases with an increase of CuO concentrations. ► Sensitivity is highly dependent on the concentrations of CuO nanoflakes.

  17. Synthesis and concentration dependent antibacterial activities of CuO nanoflakes

    International Nuclear Information System (INIS)

    Pandiyarajan, T.; Udayabhaskar, R.; Vignesh, S.; James, R. Arthur; Karthikeyan, B.

    2013-01-01

    We report, synthesis and antibacterial activities of CuO nanoflakes. CuO nanoparticles are prepared at room temperature through sol–gel method. X-ray diffraction studies show the particles are monoclinic (crystalline) in nature. Scanning electron microscopy (SEM) images clearly show that the prepared particles are flake like in structure. Fourier transform infrared (FTIR) spectra exhibits three different bands that correspond to the A u and B u modes. Antibacterial studies were performed on Shigella flexneri, Staphylococcus aureus, Staphylococcus epidermidis, Salmonella typhimurium, Bacillus subtilis, Escherichia coli, Vibrio cholera, Pseudomonas aeruginosa and Aeromonas liquefaciens bacterial strains. Among these bacterial strains, S. flexneri and B. subtilis are most sensitive to copper oxide nanoparticles than the positive control (Penicillin G) and S. typhimurium strain shows the less sensitive. Results show that sensitivity is highly dependent on the concentrations of CuO nanoflakes. - Highlights: ► CuO nanoflakes are prepared through simple sol–gel method at room temperature. ► Bacterial strains are highly affected by CuO nanoflakes than the positive control. ► Zone of inhibition increases with an increase of CuO concentrations. ► Sensitivity is highly dependent on the concentrations of CuO nanoflakes

  18. Student Engagement: Rhetoric and Reality

    Science.gov (United States)

    Baron, Paula; Corbin, Lillian

    2012-01-01

    Recently, there has been much interest in higher education literature and policy on the concepts of student engagement and disengagement. While most academic writings recognise the significance of student engagement, they have tended to concentrate on it in relation to academic activities. Increasingly, universities are "cascading" down…

  19. Social stress engages opioid regulation of locus coeruleus norepinephrine neurons and induces a state of cellular and physical opiate dependence.

    Science.gov (United States)

    Chaijale, Nayla N; Curtis, Andre L; Wood, Susan K; Zhang, Xiao-Yan; Bhatnagar, Seema; Reyes, Beverly As; Van Bockstaele, Elisabeth J; Valentino, Rita J

    2013-09-01

    Stress is implicated in diverse psychiatric disorders including substance abuse. The locus coeruleus-norepinephrine (LC-NE) system is a major stress response system that is also a point of intersection between stress neuromediators and endogenous opioids and so may be a site at which stress can influence drug-taking behaviors. As social stress is a common stressor for humans, this study characterized the enduring impact of repeated social stress on LC neuronal activity. Rats were exposed to five daily consecutive sessions of social stress using the resident-intruder model or control manipulation. LC discharge rate recorded 2 days after the last manipulation was decreased in stressed rats compared with controls. By 10 days after the last manipulation, LC rates were comparable between groups. Systemic administration of the opiate antagonist, naloxone, robustly increased LC discharge rate in a manner suggestive of opiate withdrawal, selectively in stressed rats when administered 2 or 10 days after the last manipulation. This was accompanied by behavioral signs of mild opiate withdrawal. Western blot and electron microscopic studies indicated that repeated social stress decreased corticotropin-releasing factor type 1 receptor and increased μ-opioid receptor levels in the LC. Together, the results suggest that repeated social stress engages endogenous opioid modulation of LC activity and induces signs of cellular and physical opiate dependence that endure after the stress. These cellular effects may predispose individuals with a history of repeated social stress to substance abuse behaviors.

  20. Bisphenol A impairs the memory function and glutamatergic homeostasis in a sex-dependent manner in mice: Beneficial effects of diphenyl diselenide.

    Science.gov (United States)

    Jardim, Natália S; Sartori, Glaúbia; Sari, Marcel H M; Müller, Sabrina G; Nogueira, Cristina W

    2017-08-15

    Bisphenol A (BPA) is a compound integrated in commodities, which consequently increases the human exposure to this toxicant. The deleterious effects of BPA exposure during periods of brain development have been documented mainly concerning the impairment in memory functions. Diphenyl diselenide (PhSe) 2 , an organoselenium compound, shows protective/restorative effects against memory deficits in experimental models. Thus, this study investigated the effects of (PhSe) 2 on the memory impairments induced by BPA exposure to male and female mice and the possible involvement of glutamatergic system in these effects. Three-week-old male and female Swiss mice received BPA (5mg/kg), intragastrically, from 21st to 60th postnatal day. After, the animals were intragastrically treated with (PhSe) 2 (1mg/kg) during seven days. The mice performed the behavioral memory tests and the [ 3 H] glutamate uptake and NMDA receptor subunits (2A and 2B) analyses were carried out in the hippocampus and cerebral cortex of mice. The results demonstrated that the BPA exposure induced impairment of object recognition memory in both sexes. However, it caused impairments in spatial memory in female and in the passive avoidance memory in male mice. Besides, BPA caused a decrease in the [ 3 H] glutamate uptake and NMDA receptor subunit levels in the cortical and hippocampal regions depending on the sex. Treatment with (PhSe) 2 reversed in a sex-independent manner the behavioral impairments and molecular alterations. In conclusion, BPA had a negative effect in different memory types as well as in the glutamatergic parameters in a sex-dependent manner and (PhSe) 2 treatment was effective against these alterations. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. DOC concentrations across a depth-dependent light gradient on a Caribbean coral reef

    Directory of Open Access Journals (Sweden)

    Benjamin Mueller

    2017-06-01

    Full Text Available Photosynthates released by benthic primary producers (BPP, such as reef algae and scleractinian corals, fuel the dissolved organic carbon (DOC production on tropical coral reefs. DOC concentrations near BPP have repeatedly been observed to be elevated compared to those in the surrounding water column. As the DOC release of BPP increases with increasing light availability, elevated DOC concentrations near them will, in part, also depend on light availability. Consequently, DOC concentrations are likely to be higher on the shallow, well-lit reef terrace than in deeper sections on the fore reef slope. We measured in situ DOC concentrations and light intensity in close proximity to the reef alga Dictyota sp. and the scleractinian coral Orbicella faveolata along a depth-dependent light gradient from 5 to 20 m depth and compared these to background concentrations in the water column. At 10 m (intermediate light, DOC concentrations near Dictyota sp. were elevated by 15 µmol C L−1 compared to background concentrations in the water column, but not at 5 and 20 m (high and low light, respectively, or near O. faveolata at any of the tested depths. DOC concentrations did not differ between depths and thereby light environments for any of the tested water types. However, water type and depth appear to jointly affect in situ DOC concentrations across the tested depth-dependent light gradient. Corroborative ex situ measurements of excitation pressure on photosystem II suggest that photoinhibition in Dictyota sp. is likely to occur at light intensities that are commonly present on Curaçaoan coral reefs under high light levels at 5 m depth during midday. Photoinhibition may have thereby reduced the DOC release of Dictyota sp. and DOC concentrations in its close proximity. Our results indicate that the occurrence of elevated DOC concentrations did not follow a natural light gradient across depth. Instead, a combination of multiple factors, such as water type

  2. DOC concentrations across a depth-dependent light gradient on a Caribbean coral reef.

    Science.gov (United States)

    Mueller, Benjamin; Meesters, Erik H; van Duyl, Fleur C

    2017-01-01

    Photosynthates released by benthic primary producers (BPP), such as reef algae and scleractinian corals, fuel the dissolved organic carbon (DOC) production on tropical coral reefs. DOC concentrations near BPP have repeatedly been observed to be elevated compared to those in the surrounding water column. As the DOC release of BPP increases with increasing light availability, elevated DOC concentrations near them will, in part, also depend on light availability. Consequently, DOC concentrations are likely to be higher on the shallow, well-lit reef terrace than in deeper sections on the fore reef slope. We measured in situ DOC concentrations and light intensity in close proximity to the reef alga Dictyota sp. and the scleractinian coral Orbicella faveolata along a depth-dependent light gradient from 5 to 20 m depth and compared these to background concentrations in the water column. At 10 m (intermediate light), DOC concentrations near Dictyota sp. were elevated by 15 µmol C L -1 compared to background concentrations in the water column, but not at 5 and 20 m (high and low light, respectively), or near O. faveolata at any of the tested depths. DOC concentrations did not differ between depths and thereby light environments for any of the tested water types. However, water type and depth appear to jointly affect in situ DOC concentrations across the tested depth-dependent light gradient. Corroborative ex situ measurements of excitation pressure on photosystem II suggest that photoinhibition in Dictyota sp. is likely to occur at light intensities that are commonly present on Curaçaoan coral reefs under high light levels at 5 m depth during midday. Photoinhibition may have thereby reduced the DOC release of Dictyota sp. and DOC concentrations in its close proximity. Our results indicate that the occurrence of elevated DOC concentrations did not follow a natural light gradient across depth. Instead, a combination of multiple factors, such as water type, light

  3. Mechanism of bactericidal activity of Silver Nitrate - a concentration dependent bi-functional molecule

    Directory of Open Access Journals (Sweden)

    Sureshbabu Ram Kumar Pandian

    2010-10-01

    Full Text Available Silver nitrate imparts different functions on bacteria depending upon its concentration. At lower concentration it induced synthesis of nanoparticles, whereas at higher concentrations it induced cell death. Bacillus licheniformis was used as model system. The MIC was 5 mM, and it induced catalase production, apoptotic body formation and DNA fragmentation.

  4. Regulation of AKT phosphorylation at Ser473 and Thr308 by endoplasmic reticulum stress modulates substrate specificity in a severity dependent manner.

    Directory of Open Access Journals (Sweden)

    Hong Wa Yung

    2011-03-01

    Full Text Available Endoplasmic reticulum (ER stress is a common factor in the pathophysiology of diverse human diseases that are characterised by contrasting cellular behaviours, from proliferation in cancer to apoptosis in neurodegenerative disorders. Coincidently, dysregulation of AKT/PKB activity, which is the central regulator of cell growth, proliferation and survival, is often associated with the same diseases. Here, we demonstrate that ER stress modulates AKT substrate specificity in a severity-dependent manner, as shown by phospho-specific antibodies against known AKT targets. ER stress also reduces both total and phosphorylated AKT in a severity-dependent manner, without affecting activity of the upstream kinase PDK1. Normalisation to total AKT revealed that under ER stress phosphorylation of Thr308 is suppressed while that of Ser473 is increased. ER stress induces GRP78, and siRNA-mediated knock-down of GRP78 enhances phosphorylation at Ser473 by 3.6 fold, but not at Thr308. Substrate specificity is again altered. An in-situ proximity ligation assay revealed a physical interaction between GRP78 and AKT at the plasma membrane of cells following induction of ER stress. Staining was weak in cells with normal nuclear morphology but stronger in those displaying rounded, condensed nuclei. Co-immunoprecipitation of GRP78 and P-AKT(Ser473 confirmed the immuno-complex consists of non-phosphorylated AKT (Ser473 and Thr308. The interaction is likely specific as AKT did not bind to all molecular chaperones, and GRP78 did not bind to p70 S6 kinase. These findings provide one mechanistic explanation for how ER stress contributes to human pathologies demonstrating contrasting cell fates via modulation of AKT signalling.

  5. Regulation of AKT Phosphorylation at Ser473 and Thr308 by Endoplasmic Reticulum Stress Modulates Substrate Specificity in a Severity Dependent Manner

    Science.gov (United States)

    Yung, Hong Wa

    2011-01-01

    Endoplasmic reticulum (ER) stress is a common factor in the pathophysiology of diverse human diseases that are characterised by contrasting cellular behaviours, from proliferation in cancer to apoptosis in neurodegenerative disorders. Coincidently, dysregulation of AKT/PKB activity, which is the central regulator of cell growth, proliferation and survival, is often associated with the same diseases. Here, we demonstrate that ER stress modulates AKT substrate specificity in a severity-dependent manner, as shown by phospho-specific antibodies against known AKT targets. ER stress also reduces both total and phosphorylated AKT in a severity-dependent manner, without affecting activity of the upstream kinase PDK1. Normalisation to total AKT revealed that under ER stress phosphorylation of Thr308 is suppressed while that of Ser473 is increased. ER stress induces GRP78, and siRNA-mediated knock-down of GRP78 enhances phosphorylation at Ser473 by 3.6 fold, but not at Thr308. Substrate specificity is again altered. An in-situ proximity ligation assay revealed a physical interaction between GRP78 and AKT at the plasma membrane of cells following induction of ER stress. Staining was weak in cells with normal nuclear morphology but stronger in those displaying rounded, condensed nuclei. Co-immunoprecipitation of GRP78 and P-AKT(Ser473) confirmed the immuno-complex consists of non-phosphorylated AKT (Ser473 and Thr308). The interaction is likely specific as AKT did not bind to all molecular chaperones, and GRP78 did not bind to p70 S6 kinase. These findings provide one mechanistic explanation for how ER stress contributes to human pathologies demonstrating contrasting cell fates via modulation of AKT signalling. PMID:21445305

  6. Do children with obesity have worse table manners? Associations between child table manners, weight status and weight gain.

    Science.gov (United States)

    Briones, Naomi F; Cesaro, Robert J; Appugliese, Danielle P; Miller, Alison L; Rosenblum, Katherine L; Pesch, Megan H

    2018-06-01

    Children with obesity experience stigma stemming from stereotypes, one such stereotype is that people with obesity are "sloppy" or have poor manners. Teaching children "proper table manners" has been proposed as an obesity prevention strategy. Little is known about the association between children's weight status and table manners. To examine correlates of child table manners and to examine the association of child table manners with child obese weight status and prospective change in child body mass index z-score (BMIz). Mother-child dyads (N = 228) participated in a videotaped laboratory eating task with cupcakes. Coding schemes to capture child table manners (making crumbs, chewing with mouth open, getting food on face, shoving food in mouth, slouching, and getting out of seat), and maternal attentiveness to child table manners, were reliably applied. Anthropometrics were measured at baseline and at follow-up two years later. Regression analyses examined the association of participant characteristics with child table manners, as well as the associations of child table manners with child obese weight status, and prospective change in BMIz/year. Predictors of poorer child table manners were younger child age, greater cupcake consumption, and greater maternal attentiveness to child table manners. Poorer child table manners were not associated with child obese (vs. not) weight status, but were associated with a prospective decrease in BMIz/year in children with overweight/obesity. Obesity interventions to improve table manners may be perpetuating unfavorable stereotypes and stigma. Future work investigating these associations is warranted to inform childhood obesity guidelines around table manners. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Concentration-dependent fluorescence live-cell imaging and tracking of intracellular nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Ji Hye; Joo, Sang-Woo [Department of Chemistry, Soongsil University, Seoul 156-743 (Korea, Republic of); Cho, Keunchang [Logos Biosystems, Incorporated, Anyang 431-070 (Korea, Republic of); Lee, So Yeong, E-mail: leeso@snu.ac.kr, E-mail: sjoo@ssu.ac.kr [Laboratory of Pharmacology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 151-742 (Korea, Republic of)

    2011-06-10

    Using live-cell imaging techniques we investigated concentration-dependent intracellular movements of fluorescence nanoparticles (NPs) in real-time after their entry into HeLa cells via incubation. Intracellular particle traces appeared to be a mixture of both random and fairly unidirectional movements of the particles. At rather low concentrations of NPs, a majority of the non-random intracellular particle trajectories are assumed to mostly go along microtubule networks after endocytosis, as evidenced from the inhibition test with nocodazole. On the other hand, as the concentrations of NPs increased, random motions were more frequently observed inside the cells.

  8. Concentration-dependent fluorescence live-cell imaging and tracking of intracellular nanoparticles

    International Nuclear Information System (INIS)

    Seo, Ji Hye; Joo, Sang-Woo; Cho, Keunchang; Lee, So Yeong

    2011-01-01

    Using live-cell imaging techniques we investigated concentration-dependent intracellular movements of fluorescence nanoparticles (NPs) in real-time after their entry into HeLa cells via incubation. Intracellular particle traces appeared to be a mixture of both random and fairly unidirectional movements of the particles. At rather low concentrations of NPs, a majority of the non-random intracellular particle trajectories are assumed to mostly go along microtubule networks after endocytosis, as evidenced from the inhibition test with nocodazole. On the other hand, as the concentrations of NPs increased, random motions were more frequently observed inside the cells.

  9. Hydrogen sulfide reduces neutrophil recruitment in hind-limb ischemia-reperfusion injury in an L-selectin and ADAM-17 dependent manner

    Science.gov (United States)

    Ball, Carissa J.; Reiffel, Alyssa J.; Chintalapani, Sathvika; Kim, Minsoo; Spector, Jason A.; King, Michael R.

    2012-01-01

    Background Reperfusion following ischemia leads to neutrophil recruitment injured tissue. Selectins and β2 integrins regulate neutrophil interaction with the endothelium during neutrophil rolling and firm adhesion. Excessive neutrophil infiltration into tissue is thought to contribute to IRI damage. NaHS mitigates the damage caused by ischemia-reperfusion injury (IRI). This study's objective was to determine the effect of hydrogen sulfide (NaHS) on neutrophil adhesion receptor expression. Methods Human neutrophils were either left untreated or incubated in 20 μM NaHS, and/or 50 μg/mL pharmacological ADAM-17 inhibitor TAPI-0; activated by IL-8, fMLP, or TNF-α; and labeled against PSGL-1, LFA-1, Mac-1 α, L-selectin and β2 integrin epitopes CBRM1/5 or KIM127 for flow cytometry. Cohorts of 3 C57BL/6 mice received an intravenous dose of saline vehicle, or 20 μM NaHS with or without 50 μg/mL TAPI-0 before unilateral tourniquet induced hind-limb ischemia for 3 hours followed by 3 hours of reperfusion. Bilateral gastrocnemius muscles were processed for histology before neutrophil infiltration quantification. Results NaHS treatment significantly increased L-selectin shedding from human neutrophils following activation by fMLP and IL-8 in an ADAM-17 dependent manner. Mice treated with NaHS to raise bloodstream concentration by 20 μM prior to ischemia or reperfusion showed a significant reduction in neutrophil recruitment into skeletal muscle tissue following tourniquet-induced hindlimb IRI. Conclusions NaHS administration results in the downregulation of L-selectin expression in activated human neutrophils. This leads to a reduction in neutrophil extravasation and tissue infiltration and may partially account for the protective effects of NaHS seen in the setting of IRI. PMID:23446563

  10. Serum-dependent expression of promyelocytic leukemia protein suppresses propagation of influenza virus

    International Nuclear Information System (INIS)

    Iki, Shigeo; Yokota, Shin-ichi; Okabayashi, Tamaki; Yokosawa, Noriko; Nagata, Kyosuke; Fujii, Nobuhiro

    2005-01-01

    The rate of propagation of influenza virus in human adenocarcinoma Caco-2 cells was found to negatively correlate with the concentration of fetal bovine serum (FBS) in the culture medium. Virus replicated more rapidly at lower FBS concentrations (0 or 2%) than at higher concentrations (10 or 20%) during an early stage of infection. Basal and interferon (IFN)-induced levels of typical IFN-inducible anti-viral proteins, such as 2',5'-oligoadenylate synthetase, dsRNA-activated protein kinase and MxA, were unaffected by variation in FBS concentrations. But promyelocytic leukemia protein (PML) was expressed in a serum-dependent manner. In particular, the 65 to 70 kDa isoform of PML was markedly upregulated following the addition of serum. In contrast, other isoforms were induced by IFN treatment, and weakly induced by FBS concentrations. Immunofluorescence microscopy indicated that PML was mainly formed nuclear bodies in Caco-2 cells at various FBS concentrations, and the levels of the PML-nuclear bodies were upregulated by FBS. Overexpression of PML isoform consisting of 560 or 633 amino acid residues by transfection of expression plasmid results in significantly delayed viral replication rate in Caco-2 cells. On the other hand, downregulation of PML expression by RNAi enhanced viral replication. These results indicate that PML isoforms which are expressed in a serum-dependent manner suppress the propagation of influenza virus at an early stage of infection

  11. The Probiotic Lactobacillus Prevents Citrobacter rodentium-Induced Murine Colitis in a TLR2-Dependent Manner.

    Science.gov (United States)

    Ryu, Seung-Hyun; Park, Jong-Hyung; Choi, Soo-Young; Jeon, Hee-Yeon; Park, Jin-Il; Kim, Jun-Young; Ham, Seung-Hoon; Choi, Yang-Kyu

    2016-07-28

    The main objective of this study was to investigate whether Lactobacillus rhamnosus GG (LGG) ameliorated the effects of Citrobactor rodentium infection in Toll-like receptor 2 (TLR2) knockout (KO) and TLR4 KO mice, as well as in wild-type C57BL/6 (B6) mice. TLR2 KO, TLR4 KO, and B6 mice were divided into three groups per each strain. Each group had an uninfected control group (n = 5), C. rodentium-infected group (n = 8), and LGG-pretreated C. rodentium-infected group (n = 8). The survival rate of B6 mice infected with C. rodentium was higher when pretreated with LGG. Pretreatment with LGG ameliorated C. rodentium-induced mucosal hyperplasia in B6 and TLR4 KO mice. However, in C-rodentium-infected TLR2 KO mice, mucosal hyperplasia persisted, regardless of pretreatment with LGG. In addition, LGG-pretreated B6 and TLR4 KO mice showed a decrease in spleen weight and downregulation of tumor necrosis factor alpha, interferon gamma, and monocyte chemotactic protein 1 mRNA expression compared with the non-pretreated group. In contrast, such changes were not observed in TLR2 KO mice, regardless of pretreatment with LGG. From the above results, we conclude that pretreatment with LGG ameliorates C. rodentium-induced colitis in B6 and TLR4 KO mice, but not in TLR2 KO mice. Therefore, LGG protects mice from C. rodentium-induced colitis in a TLR2-dependent manner.

  12. Phosphate regulates chondrogenesis in a biphasic and maturation-dependent manner.

    Science.gov (United States)

    Wu, Biming; Durisin, Emily K; Decker, Joseph T; Ural, Evran E; Shea, Lonnie D; Coleman, Rhima M

    Inorganic phosphate (Pi) has been recognized as an important signaling molecule that modulates chondrocyte maturation and cartilage mineralization. However, conclusive experimental evidence for its involvement in early chondrogenesis is still lacking. Here, using high-density monolayer (2D) and pellet (3D) culture models of chondrogenic ATDC5 cells, we demonstrate that the cell response to Pi does not correlate with the Pi concentration in the culture medium but is better predicted by the availability of Pi on a per cell basis (Pi abundance). Both culture models were treated with ITS+, 10mM β-glycerophosphate (βGP), or ITS+/10mM βGP, which resulted in three levels of Pi abundance in cultures: basal (Pi/DNA 60ng/µg). In chondrogenic medium alone, the abundance levels were at the basal level in 2D culture and moderate in 3D cultures. The addition of 10mM βGP resulted in moderate abundance in 2D and high abundance in 3D cultures. Moderate Pi abundance enhanced early chondrogenesis and production of aggrecan and type II collagen whereas high Pi abundance inhibited chondrogenic differentiation and induced rapid mineralization. Inhibition of sodium phosphate transporters reduced phosphate-induced expression of chondrogenic markers. When 3D ITS+/βGP cultures were treated with levamisole to reduce ALP activity, Pi abundance was decreased to moderate levels, which resulted in significant upregulation of chondrogenic markers, similar to the response in 2D cultures. Delay of phosphate delivery until after early chondrogenesis occurs (7 days) no longer enhanced chondrogenesis, but instead accelerated hypertrophy and mineralization. Together, our data highlights the dependence of chondroprogenitor cell response to Pi on its availability to individual cells and the chondrogenic maturation stage of these cells and suggest that appropriate temporal delivery of phosphate to ATDC5 cells in 3D cultures represents a rapid model for mechanistic studies into the effects of

  13. Concentration dependence of biotransformation in fish liver S9: Optimizing substrate concentrations to estimate hepatic clearance for bioaccumulation assessment.

    Science.gov (United States)

    Lo, Justin C; Allard, Gayatri N; Otton, S Victoria; Campbell, David A; Gobas, Frank A P C

    2015-12-01

    In vitro bioassays to estimate biotransformation rate constants of contaminants in fish are currently being investigated to improve bioaccumulation assessments of hydrophobic contaminants. The present study investigates the relationship between chemical substrate concentration and in vitro biotransformation rate of 4 environmental contaminants (9-methylanthracene, pyrene, chrysene, and benzo[a]pyrene) in rainbow trout (Oncorhynchus mykiss) liver S9 fractions and methods to determine maximum first-order biotransformation rate constants. Substrate depletion experiments using a series of initial substrate concentrations showed that in vitro biotransformation rates exhibit strong concentration dependence, consistent with a Michaelis-Menten kinetic model. The results indicate that depletion rate constants measured at initial substrate concentrations of 1 μM (a current convention) could underestimate the in vitro biotransformation potential and may cause bioconcentration factors to be overestimated if in vitro biotransformation rates are used to assess bioconcentration factors in fish. Depletion rate constants measured using thin-film sorbent dosing experiments were not statistically different from the maximum depletion rate constants derived using a series of solvent delivery-based depletion experiments for 3 of the 4 test chemicals. Multiple solvent delivery-based depletion experiments at a range of initial concentrations are recommended for determining the concentration dependence of in vitro biotransformation rates in fish liver fractions, whereas a single sorbent phase dosing experiment may be able to provide reasonable approximations of maximum depletion rates of very hydrophobic substances. © 2015 SETAC.

  14. Growth and xanthan production of Xanthomonas campestris depending on the N-source concentration

    Energy Technology Data Exchange (ETDEWEB)

    Prell, A [Academy of Sciences of the Czech Republic, Prague (Czech Republic). Inst. of Microbiology; Lasik, J [Academy of Sciences of the Czech Republic, Prague (Czech Republic). Inst. of Microbiology; Konicek, J [Academy of Sciences of the Czech Republic, Prague (Czech Republic). Inst. of Microbiology; Sobotka, M [Academy of Sciences of the Czech Republic, Prague (Czech Republic). Inst. of Microbiology; Sys, J [Academy of Sciences of the Czech Republic, Prague (Czech Republic). Inst. of Microbiology

    1995-11-01

    Growth of X. campestris and production of xanthan were studied in several batch fermentations with different starting concentrations of N-source. The dependencies of growth, productivity and yields on initial N-source concentration were observed. The maximum yields in the course of cultivations were identified. (orig.)

  15. Concentration-Dependent Patterns of Leucine Incorporation by Coastal Picoplankton

    Science.gov (United States)

    Alonso, Cecilia; Pernthaler, Jakob

    2006-01-01

    Coastal pelagic environments are believed to feature concentration gradients of dissolved organic carbon at a microscale, and they are characterized by pronounced seasonal differences in substrate availability for the heterotrophic picoplankton. Microbial taxa that coexist in such habitats might thus differ in their ability to incorporate substrates at various concentrations. We investigated the incorporation patterns of leucine in four microbial lineages from the coastal North Sea at concentrations between 0.1 and 100 nM before and during a spring phytoplankton bloom. Community bulk incorporation rates and the fraction of leucine-incorporating cells in the different populations were analyzed. Significantly fewer bacterial cells incorporated the amino acid before (13 to 35%) than during (23 to 47%) the bloom at all but the highest concentration. The incorporation rate per active cell in the prebloom situation was constant above 0.1 nM added leucine, whereas it increased steeply with substrate concentration during the bloom. At both time points, a high proportion of members of the Roseobacter clade incorporated leucine at all concentrations (55 to 80% and 86 to 94%, respectively). In contrast, the fractions of leucine-incorporating cells increased substantially with substrate availability in bacteria from the SAR86 clade (8 to 31%) and from DE cluster 2 of the Flavobacteria-Sphingobacteria (14 to 33%). The incorporation patterns of marine Euryarchaeota were between these extremes (30 to 56% and 48 to 70%, respectively). Our results suggest that the contribution of microbial taxa to the turnover of particular substrates may be concentration dependent. This may help us to understand the specific niches of coexisting populations that appear to compete for the same resources. PMID:16517664

  16. The association between etanercept serum concentration and psoriasis severity is highly age-dependent.

    Science.gov (United States)

    Detrez, Iris; Van Steen, Kristel; Segaert, Siegfried; Gils, Ann

    2017-06-01

    The association between etanercept serum concentration and psoriasis disease severity is poorly investigated, and currently etanercept serum concentration monitoring that is aiming to optimize the psoriasis treatment lacks evidence. In this prospective study, we investigated the relation between etanercept exposure and disease severity via measuring etanercept concentrations at five consecutive time points in 56 psoriasis patients. Disease severity assessments included the Psoriasis Area and Severity Index (PASI), body surface area (BSA) and Physician Global Assessment (PGA), and etanercept and anti-etanercept antibody concentrations were determined every 3 months for a period of 1 year. The present study demonstrated that the association between etanercept concentration and psoriasis severity is age-dependent: when patients were stratified into three groups, patients in the youngest age group (-50 years) showed a lower PASI at a higher etanercept concentration (β = -0.26), whereas patients in the oldest age group (+59 years) showed the opposite trend (β =0.22). Similar age effects were observed in the relation of etanercept concentration with BSA ( P =0.02) and PGA ( P =0.02). The influence of age and length of time in therapy on the etanercept concentration-disease severity relation was unaffected by body mass index (BMI) or any other possible confounder. Incidence of anti-etanercept antibodies was low (2%). The age-dependent relation between etanercept serum concentrations is both unexpected and intriguing and needs further investigation. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  17. Speech Mannerisms: Games Clients Play

    Science.gov (United States)

    Morgan, Lewis B.

    1978-01-01

    This article focuses on speech mannerisms often employed by clients in a helping relationship. Eight mannerisms are presented and discussed, as well as possible interpretations. Suggestions are given to help counselors respond to them. (Author)

  18. Relationship between job demand and burnout in nurses: does it depend on work engagement?

    Science.gov (United States)

    García-Sierra, Rosa; Fernández-Castro, Jordi; Martínez-Zaragoza, Fermín

    2016-09-01

    The present study aimed to deepen the understanding of the relationships among job demands, control, social support, burnout and engagement in nurses. Burnout is a prevalent phenomenon among nurses because of the interaction between high demands and low resources, according to the job demands-resources model. A descriptive, correlational design was used in a stratified random sample of 100 nurses recruited from two Spanish hospitals. Job demand, social support, control, engagement, and burnout were measured. Data were analysed by hierarchical regression analysis. Social support is a significant predictor of nurses' engagement and demands is a predictor of nurses' burnout. Work engagement moderates the relationship between job demands and burnout. The process that leads to burnout and the process that leads to engagement are not isolated processes; engagement acts as a moderator of burnout. The prevailing paradigm in combating burnout in nursing can be changed and could be based on the enhancement of nurses' strengths through increasing engagement. © 2016 John Wiley & Sons Ltd.

  19. Determination of Concentration Dependent Diffusion Coefficients of Carbon in Expanded Austenite

    DEFF Research Database (Denmark)

    Hummelshøj, Thomas Strabo; Christiansen, Thomas; Somers, Marcel A. J.

    2008-01-01

    Abstract. In the present paper various experimental procedures to experimentally determine the concentration dependent diffusion coefficient of carbon in expanded austenite are evaluated. To this end thermogravimetric carburization was simulated for various experimental conditions and the evaluated...... composition dependent diffusivity of carbon derived from the simulated experiments was compared with the input data. The most promising procedure for an accurate determination is shown to be stepwise gaseous carburizing of thin foils in a gaseous atmosphere; the finer the stepsize, the more accurate...

  20. He-Ne laser irradiation affects proliferation of cultured rat Schwann cells in a dose-dependent manner

    International Nuclear Information System (INIS)

    Breugel, H.H.F.I. van; Bar, P.R.

    1993-01-01

    Schwann cell proliferation is considered an essential part of Wallerian degeneration after nerve damage. Laminin, an important component of the extracellular matrix and produced by Schwann cells, provides a preferred substrate for outgrowing axons. To study whether low energy (He-Ne) laser irradiation may exert a positive effect on nerve regeneration through an effect on Schwann cells, its effect was evaluated in vitro. Schwann cells were isolated from sciatic nerves of 4-5-day old Wistar rats and cultures on 96-multiwell plates. The cells were irradiated by a He-Ne laser beam. At three consecutive days, starting either at day 5 or day 8, cells were irradiated each day for 0.5, 1, 2, 5 or 10 min. Both cell number and laminin production were determined for each irradiation condition within one experiment. Schwann cells that were irradiated from day 8 on were hardly affected by laser irradiation. However, the proliferation of cells that were irradiated starting on day 5 was significantly increased after 1, 2 and 5 min of daily irradiation, compared to non-irradiated control cultures. The lamin production per cell of these Schwann cells was not significantly altered. From these results we conclude that He-Ne laser irradiation can modulate proliferation of rat Schwann cells in vitro in a dose-dependent manner. (Author)

  1. TLR3 mediates release of IL-1β and cell death in keratinocytes in a caspase-4 dependent manner.

    Science.gov (United States)

    Grimstad, Øystein; Husebye, Harald; Espevik, Terje

    2013-10-01

    Inflammation and timely cell death are important elements in host defence and healing processes. Keratinocytes express high levels of Toll-like receptor 3 (TLR3), and stimulation of the receptor with its ligand polyinosinic-polycytidylic acid (polyI:C) is a powerful signal for release of a variety of proinflammatory cytokines. Caspase-4 is required for maturation of pro-IL-1β through activation of caspase-1 in keratinocytes. TLR3 in keratinocytes was stimulated with polyI:C. Induction of messenger RNA of pro-IL-1β and inflammasomal components was measured using quantitative polymerase chain reaction methodology. Protein expression of IL-1β was analysed with ELISA and Western blot techniques. Activation of apoptotic caspases was measured with flow cytometry, and cytotoxicity was determined. TLR3 induced release of substantial amounts of pro-IL-1β in keratinocytes. NLRP3 or ASC dependent processing of IL-1β into its cleaved bioactive form was found to be minimal. The release of IL-1β was due to polyI:C induced cell death that occurred through a caspase-4 dependent manner. Caspase-1 did not seem to be involved in the polyI:C induced cytotoxicity despite that TLR3 stimulation induced activation of caspase-1. In addition, the apoptotic caspases -8, -9 and -3/7 were activated by polyI:C. TLR3 stimulation in keratinocytes induces a caspase-4 dependent release of pro-IL-1β, but further processing to active IL-1β is limited. Furthermore, TLR3 stimulation results in pyroptotic- and apoptotic cell death. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  2. Buried Messages, Hidden Meanings: Speech Mannerisms Revisited.

    Science.gov (United States)

    Morgan, Lewis B.

    1988-01-01

    Introduces counselors to 10 commonly used mannerisms of speech and the part that each mannerism plays in the communication process, especially in the counseling context. Offers suggestions on how to respond to these speech mannerisms in a straightforward and effective manner. (Author)

  3. Building towards engagement: An individual perspective

    NARCIS (Netherlands)

    Ouweneel, A.P.E.|info:eu-repo/dai/nl/314006516

    2012-01-01

    Organizations are struggling to survive, so they are dependent on the productiveness and well-being of their employees. Nowadays, work engagement – the focal construct of this thesis – is one of the most established well-being constructs within organizational psychology. Work engagement is defined

  4. Meteorological variables affect fertility rate after intrauterine artificial insemination in sheep in a seasonal-dependent manner: a 7-year study

    Science.gov (United States)

    Palacios, C.; Abecia, J. A.

    2015-05-01

    A total number of 48,088 artificial inseminations (AIs) have been controlled during seven consecutive years in 79 dairy sheep Spanish farms (41° N). Mean, maximum and minimum ambient temperatures ( Ts), temperature amplitude (TA), mean relative humidity (RH), mean solar radiation (SR) and total rainfall of each insemination day and 15 days later were recorded. Temperature-humidity index (THI) and effective temperature (ET) have been calculated. A binary logistic regression model to estimate the risk of not getting pregnant compared to getting pregnant, through the odds ratio (OR), was performed. Successful winter inseminations were carried out under higher SR ( P 1 (maximum T, ET and rainfall on AI day, and ET and rainfall on day 15), and two variables presented OR AI day and maximum T on day 15). However, the effect of meteorological factors affected fertility in opposite ways, so T becomes a protective or risk factor on fertility depending on season. In conclusion, the percentage of pregnancy after AI in sheep is significantly affected by meteorological variables in a seasonal-dependent manner, so the parameters such as temperature reverse their effects in the hot or cold seasons. A forecast of the meteorological conditions could be a useful tool when AI dates are being scheduled.

  5. Strong adhesion by regulatory T cells induces dendritic cell cytoskeletal polarization and contact-dependent lethargy.

    Science.gov (United States)

    Chen, Jiahuan; Ganguly, Anutosh; Mucsi, Ashley D; Meng, Junchen; Yan, Jiacong; Detampel, Pascal; Munro, Fay; Zhang, Zongde; Wu, Mei; Hari, Aswin; Stenner, Melanie D; Zheng, Wencheng; Kubes, Paul; Xia, Tie; Amrein, Matthias W; Qi, Hai; Shi, Yan

    2017-02-01

    Dendritic cells are targeted by regulatory T (T reg) cells, in a manner that operates as an indirect mode of T cell suppression. In this study, using a combination of single-cell force spectroscopy and structured illumination microscopy, we analyze individual T reg cell-DC interaction events and show that T reg cells exhibit strong intrinsic adhesiveness to DCs. This increased DC adhesion reduces the ability of contacted DCs to engage other antigen-specific cells. We show that this unusually strong LFA-1-dependent adhesiveness of T reg cells is caused in part by their low calpain activities, which normally release integrin-cytoskeleton linkage, and thereby reduce adhesion. Super resolution imaging reveals that such T reg cell adhesion causes sequestration of Fascin-1, an actin-bundling protein essential for immunological synapse formation, and skews Fascin-1-dependent actin polarization in DCs toward the T reg cell adhesion zone. Although it is reversible upon T reg cell disengagement, this sequestration of essential cytoskeletal components causes a lethargic state of DCs, leading to reduced T cell priming. Our results reveal a dynamic cytoskeletal component underlying T reg cell-mediated DC suppression in a contact-dependent manner. © 2017 Chen et al.

  6. A neural measure of behavioral engagement: task-residual low-frequency blood oxygenation level-dependent activity in the precuneus.

    Science.gov (United States)

    Zhang, Sheng; Li, Chiang-Shan Ray

    2010-01-15

    Brain imaging has provided a useful tool to examine the neural processes underlying human cognition. A critical question is whether and how task engagement influences the observed regional brain activations. Here we highlighted this issue and derived a neural measure of task engagement from the task-residual low-frequency blood oxygenation level-dependent (BOLD) activity in the precuneus. Using independent component analysis, we identified brain regions in the default circuit - including the precuneus and medial prefrontal cortex (mPFC) - showing greater activation during resting as compared to task residuals in 33 individuals. Time series correlations with the posterior cingulate cortex as the seed region showed that connectivity with the precuneus was significantly stronger during resting as compared to task residuals. We hypothesized that if the task-residual BOLD activity in the precuneus reflects engagement, it should account for a certain amount of variance in task-related regional brain activation. In an additional experiment of 59 individuals performing a stop signal task, we observed that the fractional amplitude of low-frequency fluctuation (fALFF) of the precuneus but not the mPFC accounted for approximately 10% of the variance in prefrontal activation related to attentional monitoring and response inhibition. Taken together, these results suggest that task-residual fALFF in the precuneus may be a potential indicator of task engagement. This measurement may serve as a useful covariate in identifying motivation-independent neural processes that underlie the pathogenesis of a psychiatric or neurological condition.

  7. Lithium concentration dependent structure and mechanics of amorphous silicon

    Energy Technology Data Exchange (ETDEWEB)

    Sitinamaluwa, H. S.; Wang, M. C.; Will, G.; Senadeera, W.; Yan, C., E-mail: c2.yan@qut.edu.au [School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology (QUT), Brisbane QLD 4001 (Australia); Zhang, S. [Centre for Clean Environment and Energy, Environmental Futures Research Institute and Griffith School of Environment, Gold Coast Campus, Griffith University, QLD 4222 (Australia)

    2016-06-28

    A better understanding of lithium-silicon alloying mechanisms and associated mechanical behavior is essential for the design of Si-based electrodes for Li-ion batteries. Unfortunately, the relationship between the dynamic mechanical response and microstructure evolution during lithiation and delithiation has not been well understood. We use molecular dynamic simulations to investigate lithiated amorphous silicon with a focus to the evolution of its microstructure, phase composition, and stress generation. The results show that the formation of Li{sub x}Si alloy phase is via different mechanisms, depending on Li concentration. In these alloy phases, the increase in Li concentration results in reduction of modulus of elasticity and fracture strength but increase in ductility in tension. For a Li{sub x}Si system with uniform Li distribution, volume change induced stress is well below the fracture strength in tension.

  8. Sorafenib modulates the radio sensitivity of hepatocellular carcinoma cells in vitro in a schedule-dependent manner

    International Nuclear Information System (INIS)

    Li, Qiaoqiao; Hu, Yonghong; Xi, Mian; He, Liru; Zhao, Lei; Liu, Mengzhong

    2012-01-01

    Hepatocellular carcinoma (HCC) has a high incidence and mortality. Radiotherapy and sorafenib have proven effective for HCC. Here, we investigated whether sorafenib modulated the response of HCC cells to irradiation in vitro, effect of timing of sorafenib, and the underlying mechanisms. Cell viability of the HCC cell lines, SMMC-7721 and Bel-7402, was examined by the 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2(4-sulfophenyl)-2 H-terazolium (MTT) assays. Clonogenic growth assays of SMMC-7721 and Bel-7402 were determined by colony formation assays. DNA damage was assessed by monitoring γ-HAX foci in irradiated cells with immunofluorescence microscopy, and cell cycle distribution changes were examined by flow cytometry. Effects of sorafenib (15 μM) added 30 min prior to radiation (pre-irradiation sorafenib) of SMMC-7721 and BEL-7402 or 24 h post-irradiation (post-irradiation sorafenib) on irradiated SMMC-7721 and BEL-7402 cells were compared to those of radiation alone or no treatment. The effect of sorafenib was dependent on its time of addition in relationship to irradiation of cells. Pre-irradiation sorafenib did not significantly affect the viability of SMMC-7221 and BEL-7402 cells compared with irradiation treatment alone. In contrast, post-irradiation sorafenib increased the sensitivity of irradiated SMMC-7221 and BEL-7402 cells significantly in a time-dependent manner. Pre-irradiation sorafenib significantly increased the surviving fraction of SMMC-7221 and BEL-7402 cells in clonogenic assays whereas post-irradiation sorafenib significantly reduced the surviving fractions of SMMC-7221 and BEL-7402 cells. SMMC-7721 cells treated with sorafenib 30 min before irradiation had significantly fewer cells with γ-H2AX foci (23.8 ± 2.9%) than SMMC-7721 cells receiving radiation alone (59.9 ± 2.4; P < 0.001). Similarly, BEL-7402 cells receiving sorafenib prior to irradiation had significantly fewer cells with γ-H2AX foci (46.4 ± 3.8%) than those

  9. Closing the Civic Engagement Gap: The Potential of Action Civics

    Science.gov (United States)

    Pope, Alexander; Stolte, Laurel; Cohen, Alison K.

    2011-01-01

    When taught in an engaging manner, civic education can help stimulate and motivate students to excel in other academic areas, while simultaneously preparing them to be active citizens in the democracy. As an initial attempt to more systematically analyze civic education practice, this article presents four case studies of projects in one action…

  10. Dependence of indoor radon concentration on the year of house construction

    International Nuclear Information System (INIS)

    Fujimoto, K.; Sanada, T.

    1999-01-01

    The dependence of indoor radon concentration on the year of house construction was studied using the results of two nationwide indoor radon surveys in Japan. The data of radon concentration in the surveys were classified into structure type as well as year of construction to obtain the current radon concentration for each structure type as a function of year of construction. The indoor radon concentration in wooden houses was found to be relatively constant with year of house construction until 1960, and then decreased, whereas the radon concentration in concrete houses increased sharply in houses constructed after 1970. The concentration in concrete houses built before 1975 was almost the same as that in contemporary wooden houses. However, the concentration in concrete houses built at present was about two times higher than that in wooden houses. The time trends found for wooden and concrete houses in the first nationwide indoor radon survey were confirmed by the second nationwide survey. In addition, these same time trends were mostly observed in the data classified into 7 districts in Japan. The increase of indoor radon concentration in concrete houses provides relatively high dose, and this increasing trend seems to continue, judging from the results of two nationwide surveys

  11. EGFR-dependent signalling reduced and p38 dependent apoptosis required by Gallic acid in Malignant Mesothelioma cells.

    Science.gov (United States)

    Demiroglu-Zergeroglu, Asuman; Candemir, Gulsife; Turhanlar, Ebru; Sagir, Fatma; Ayvali, Nurettin

    2016-12-01

    The unrestrained EGFR signalling contributes to malignant phenotype in a number of cancers including Malignant Mesotheliomas. Present study was designed to evaluate EGFR-dependent anti-proliferative and apoptotic effects of Gallic acid in transformed Mesothelial (MeT-5A) and Malignant Mesothelioma (SPC212) cells. Gallic acid reduced the viability of Malignant Mesothelioma cells in a concentration and time-dependent manner. However, viability of mesothelial cells reduced only at high concentration and longer time periods. Gallic acid restrained the activation of EGFR, ERK1/2 and AKT proteins and down regulated expression of Cyclin D and Bcl-2 genes, but upregulated the expression of p21 gene in EGF-induced SPC212 cells. GA-induced transitory G1 arrest and triggered mitochondrial and death receptor mediated apoptosis, which requires p38MAPK activation. The data provided here indicate that GA is able to inhibit EGFR dependent proliferation and survival signals and induces p38 pathway dependent apoptosis in Malignant Mesothelioma cells. On the basis of these experimental findings it is worthwhile to investigate further the biological activity of Gallic acid on other Mesothelioma cell lines harbouring aberrant EGFR signals. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  12. Thin-source concentration dependent diffusion

    International Nuclear Information System (INIS)

    Eng, G.

    1978-01-01

    The diffusion of (Ca ++ ) in NaCl has been measured for various diffusion times and for the temperature range (575 0 to 775 0 C), using a thin-source of 45 Ca tracer, rectangular geometry, and serial sectioning. The pre-diffusion surface concentration was approximately 3 x 10 16 (Ca)-atoms/cm 2 , which, for an average penetration depth of 100 to 300 μm, produces a maximum (post-diffusion) impurity concentration comparable to or greater than the intrinsic cation vacancy concentration. The high-temperature function closely matches the D 0 (T) function obtained from low impurity concentration experiments. The lower-temperature function, combined with the sudden failure of the D(C) = D 0 (1 + [C] + 0.5[C] 2 ) function at these lower temperatures, indicates the onset of a second diffusion process, one which would operate only at extremely high impurity concentrations. This low-temperature behavior is shown to be consistent with a breakdown of the conditions assumed for vacancy equilibrium

  13. Concentration-dependent oligomerization of cross-linked complexes between ferredoxin and ferredoxin–NADP+ reductase

    International Nuclear Information System (INIS)

    Kimata-Ariga, Yoko; Kubota-Kawai, Hisako; Lee, Young-Ho; Muraki, Norifumi; Ikegami, Takahisa; Kurisu, Genji; Hase, Toshiharu

    2013-01-01

    Highlights: •Cross-linked complexes of ferredoxin (Fd) and Fd–NADP + reductase form oligomers. •In the crystal structures, Fd- and FNR moieties swap across the molecules. •The complexes exhibit concentration-dependent oligomerization at sub-milimolar order. -- Abstract: Ferredoxin–NADP + reductase (FNR) forms a 1:1 complex with ferredoxin (Fd), and catalyzes the electron transfer between Fd and NADP + . In our previous study, we prepared a series of site-specifically cross-linked complexes of Fd and FNR, which showed diverse electron transfer properties. Here, we show that X-ray crystal structures of the two different Fd–FNR cross-linked complexes form oligomers by swapping Fd and FNR moieties across the molecules; one complex is a dimer from, and the other is a successive multimeric form. In order to verify whether these oligomeric structures are formed only in crystal, we investigated the possibility of the oligomerization of these complexes in solution. The mean values of the particle size of these cross-linked complexes were shown to increase with the rise of protein concentration at sub-milimolar order, whereas the size of dissociable wild-type Fd:FNR complex was unchanged as analyzed by dynamic light scattering measurement. The oligomerization products were detected by SDS–PAGE after chemical cross-linking of these complexes at the sub-milimolar concentrations. The extent and concentration-dependent profile of the oligomerizaion were differentiated between the two cross-linked complexes. These results show that these Fd–FNR cross-linked complexes exhibit concentration-dependent oligomerization, possibly through swapping of Fd and FNR moieties also in solution. These findings lead to the possibility that some native multi-domain proteins may present similar phenomenon in vivo

  14. Behaviour of trace element concentration in human organs in dependence of age and environment

    International Nuclear Information System (INIS)

    Persigehl, M.; Schicha, H.; Kasperek, K.; Feinendegen, L.E.; Kernforschungsanlage Juelich G.m.b.H.

    1977-01-01

    To study the behaviour of trace elements in dependence of age and environment, samples of skin, lung, heart, aorta, kidney, liver and brain were assayed for concentrations of Fe, Zn, Rb, Co, Cr, Se, Sc, Sb, Cs, Al and partly Eu. All samples were dried at 100 deg C for two days. Instrumental neutron-activation analysis was used to determine the element concentrations. The neutron flux was 5 x 10 13 n cm -2 sec -1 . After decay of the short lived radioisotopes, the Al-concentration was measured following a second irradiation of 1 minute and directly comparing with a standard sample. Nearly all element concentrations changed with processing age, but they showed no clear correlation to either parameter assessed. The non-essential elements Se, Sb and Sc were increasingly concentrated in all organs except the skin. Comparing lung samples of patients from highly industrialized regions with those of lesser industrialization, the elements Sc, Al, Sb, Eu and Co were accumulated by a factor of 10 to 100. Thus the concentrations of trace elements in human organism also depend on the degree of industrialization. (T.G.)

  15. 3-Phosphoinositide-dependent PDK1 negatively regulates transforming growth factor-beta-induced signaling in a kinase-dependent manner through physical interaction with Smad proteins.

    Science.gov (United States)

    Seong, Hyun-A; Jung, Haiyoung; Kim, Kyong-Tai; Ha, Hyunjung

    2007-04-20

    We have reported previously that PDK1 physically interacts with STRAP, a transforming growth factor-beta (TGF-beta) receptor-interacting protein, and enhances STRAP-induced inhibition of TGF-beta signaling. In this study we show that PDK1 coimmunoprecipitates with Smad proteins, including Smad2, Smad3, Smad4, and Smad7, and that this association is mediated by the pleckstrin homology domain of PDK1. The association between PDK1 and Smad proteins is increased by insulin treatment but decreased by TGF-beta treatment. Analysis of the interacting proteins shows that Smad proteins enhance PDK1 kinase activity by removing 14-3-3, a negative regulator of PDK1, from the PDK1-14-3-3 complex. Knockdown of endogenous Smad proteins, including Smad3 and Smad7, by transfection with small interfering RNA produced the opposite trend and decreased PDK1 activity, protein kinase B/Akt phosphorylation, and Bad phosphorylation. Moreover, coexpression of Smad proteins and wild-type PDK1 inhibits TGF-beta-induced transcription, as well as TGF-beta-mediated biological functions, such as apoptosis and cell growth arrest. Inhibition was dose-dependent on PDK1, but no inhibition was observed in the presence of an inactive kinase-dead PDK1 mutant. In addition, confocal microscopy showed that wild-type PDK1 prevents translocation of Smad3 and Smad4 from the cytoplasm to the nucleus, as well as the redistribution of Smad7 from the nucleus to the cytoplasm in response to TGF-beta. Taken together, our results suggest that PDK1 negatively regulates TGF-beta-mediated signaling in a PDK1 kinase-dependent manner via a direct physical interaction with Smad proteins and that Smad proteins can act as potential positive regulators of PDK1.

  16. Cholecalciferol attenuates perseverative behavior associated with developmental alcohol exposure in rats in a dose-dependent manner.

    Science.gov (United States)

    Idrus, N M; Happer, J P; Thomas, J D

    2013-07-01

    Alcohol is a known teratogen that is estimated to affect 2-5% of the births in the U.S. Prenatal alcohol exposure can produce physical features such as facial dysmorphology, physiological alterations such as cell loss in the central nervous system (CNS), and behavioral changes that include hyperactivity, cognitive deficits, and motor dysfunction. The range of effects associated with prenatal alcohol exposure is referred to as fetal alcohol spectrum disorders (FASD). Despite preventative measures, some women continue to drink while pregnant. Therefore, identifying interventions that reduce the severity of FASD is critical. This study investigated one such potential intervention, vitamin D3, a nutrient that exerts neuroprotective properties. The present study determined whether cholecalciferol, a common vitamin D3 nutritional supplement, could serve as a means of mitigating alcohol-related learning deficits. Using a rat model of FASD, cholecalciferol was given before, during, and after 3rd trimester equivalent alcohol exposure. Three weeks after cholecalciferol treatment, subjects were tested on a serial spatial discrimination reversal learning task. Animals exposed to ethanol committed significantly more errors compared to controls. Cholecalciferol treatment reduced perseverative behavior that is associated with developmental alcohol exposure in a dose-dependent manner. These data have important implications for the treatment of FASD and suggest that cholecalciferol may reduce some aspects of FASD. This article is part of a Special Issue entitled 'Vitamin D Workshop'. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Respiratory function in healthy ever-smokers is impaired by smoking habits in a dose-dependent manner.

    Science.gov (United States)

    Osanai, Shinobu; Ogasa, Toshiyuki; Sumitomo, Kazuhiro; Hasebe, Naoyuki

    2018-01-01

    There is limited information about the respiratory function of ever-smokers without lung disorders. We sought to assess the effects of smoking habits on respiratory function in subjects without lung disorders. Subjects were recruited from among patients without any evidence of respiratory disorders who visited rural primary care clinics. Each participant was asked to answer a questionnaire that included questions smoking history. Their forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured. We analyzed 802 subjects (364 men and 438 women). The means of the lambda-mu-sigma method derived z-score of FEV1 (zFEV1) both in current-smokers and ex-smokers were lower than that in never-smokers. The mean zFEV1 in the ever-smokers with more than 30 pack-years of smoking history were lower than that in the ever-smokers with less smoking history. Univariate analysis showed that there were significant negative correlations between pack-years and zFEV1 both in the ex-smokers and current-smokers. There was no significant correlation between the duration of smoking cessation and zFEV1 in the ex-smokers. Our data suggests that respiratory function in healthy ever-smokers is decreased based on smoking habits in a dose-dependent manner. Even after a long period of smoking cessation, the decreased respiratory function seems to be maintained in ex-smokers. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  18. Ofloxacin induces apoptosis in microencapsulated juvenile rabbit chondrocytes by caspase-8-dependent mitochondrial pathway

    International Nuclear Information System (INIS)

    Sheng Zhiguo; Cao Xiaojuan; Peng Shuangqing; Wang Changyong; Li Qianqian; Wang Yimei; Liu Mifeng

    2008-01-01

    Quinolones (QNs)-induced arthropathy is an important toxic effect in immature animals leading to restriction of their therapeutic use in pediatrics. However, the exact mechanism still remains unclear. Recently, we have demonstrated that ofloxacin, a typical QN, induces apoptosis of alginate microencapsulated juvenile rabbit joint chondrocytes by disturbing the β 1 integrin functions and inactivating the ERK/MAPK signaling pathway. In this study, we extend our initial observations to further elucidate the mechanism(s) of ofloxacin-induced apoptosis by utilizing specific caspase inhibitors. Pretreatment with both caspase-9-specific inhibitor zLEHD-fmk and caspase-8 inhibitor zIETD-fmk attenuated ofloxacin-induced apoptosis and activation of caspase-3 of chondrocyte in a concentration-dependent manner, as determined by fluorescent dye staining, enzyme activity assay and immunoblotting. Furthermore, the activation of caspase-9, -8 and -3 stimulated by ofloxacin was significantly inhibited in the presence of zIETD-fmk while pretreatment with zLEHD-fmk only blocked the activation of caspase-9 and -3. Ofloxacin also stimulated a concentration-dependent translocation of cytochrome c from mitochondria into the cytosol and a decrease of mitochondrial transmembrane potential, which was completely inhibited by zIETD-fmk. In addition, ofloxacin was found to increase the level of Bax, tBid, p53 in a concentration- and time-dependent manner. Taken together, The current results indicate that the caspase-8-dependent mitochondrial pathway is primarily involved in the ofloxacin-induced apoptosis of microencapsulated juvenile rabbit joint chondrocytes

  19. 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

  20. 26 CFR 1.183-2 - Activity not engaged in for profit defined.

    Science.gov (United States)

    2010-04-01

    ... determination whether an activity is engaged in for profit is to be made by reference to objective standards... the activity in a businesslike manner and maintains complete and accurate books and records may... accepted business, economic, and scientific practices, or consultation with those who are expert therein...

  1. Kant, Xunzi and the Artificiality of Manners

    Directory of Open Access Journals (Sweden)

    Anja BERNINGER

    2017-01-01

    Full Text Available Both Chinese and Western philosophers have argued for the ethical importance of manners. Their approaches are sometimes criticized on the grounds that manners are artificial. I compare Xunzi’s and Kant’s responses to this claim, and discuss the relevance of both positions for the development of a theory of manners. I show that there is no single artificiality claim, but rather four different claims: the claim that polite behavior lacks spontaneity, the claim that it is insincere, the claim that it goes against human nature, and the claim that it is arbitrary. While Kant is mainly concerned with the insincerity claim, Xunzi focusses on the claim that manners are arbitrary rules. Because of their different understandings of the function of manners both authors only provide a partial answer to the artificiality claim. To arrive at a full account of manners both perspectives must be combined.

  2. Concentration and size dependence of peak wavelength shift on quantum dots in colloidal suspension

    Science.gov (United States)

    Rinehart, Benjamin S.; Cao, Caroline G. L.

    2016-08-01

    Quantum dots (QDs) are semiconductor nanocrystals that have significant advantages over organic fluorophores, including their extremely narrow Gaussian emission bands and broad absorption bands. Thus, QDs have a wide range of potential applications, such as in quantum computing, photovoltaic cells, biological sensing, and electronics. For these applications, aliasing provides a detrimental effect on signal identification efficiency. This can be avoided through characterization of the QD fluorescence signals. Characterization of the emissivity of CdTe QDs as a function of concentration (1 to 10 mg/ml aqueous) was conducted on 12 commercially available CdTe QDs (emission peaks 550 to 730 nm). The samples were excited by a 50-mW 405-nm laser with emission collected via a free-space CCD spectrometer. All QDs showed a redshift effect as concentration increased. On average, the CdTe QDs exhibited a maximum shift of +35.6 nm at 10 mg/ml and a minimum shift of +27.24 nm at 1 mg/ml, indicating a concentration dependence for shift magnitude. The concentration-dependent redshift function can be used to predict emission response as QD concentration is changed in a complex system.

  3. PRMT1 and PRMT4 Regulate Oxidative Stress-Induced Retinal Pigment Epithelial Cell Damage in SIRT1-Dependent and SIRT1-Independent Manners

    Directory of Open Access Journals (Sweden)

    Dong-Il Kim

    2015-01-01

    Full Text Available Oxidative stress-induced retinal pigment epithelial (RPE cell damage is involved in the progression of diabetic retinopathy. Arginine methylation catalyzed by protein arginine methyltransferases (PRMTs has emerged as an important histone modification involved in diverse diseases. Sirtuin (SIRT1 is a protein deacetylase implicated in the onset of metabolic diseases. Therefore, we examined the roles of type I PRMTs and their relationship with SIRT1 in human RPE cells under H2O2-induced oxidative stress. H2O2 treatment increased PRMT1 and PRMT4 expression but decreased SIRT1 expression. Similar to H2O2 treatment, PRMT1 or PRMT4 overexpression increased RPE cell damage. Moreover, the H2O2-induced RPE cell damage was attenuated by PRMT1 or PRMT4 knockdown and SIRT1 overexpression. In this study, we revealed that SIRT1 expression was regulated by PRMT1 but not by PRMT4. Finally, we found that PRMT1 and PRMT4 expression is increased in the RPE layer of streptozotocin-treated rats. Taken together, we demonstrated that oxidative stress induces apoptosis both via PRMT1 in a SIRT1-dependent manner and via PRMT4 in a SIRT1-independent manner. The inhibition of the expression of type I PRMTs, especially PRMT1 and PRMT4, and increased SIRT1 could be therapeutic approaches for diabetic retinopathy.

  4. Inflammatory Human Umbilical Cord-Derived Mesenchymal Stem Cells Promote Stem Cell-Like Characteristics of Cancer Cells in an IL-1β-Dependent Manner

    Directory of Open Access Journals (Sweden)

    Xiaohe Luo

    2018-01-01

    Full Text Available To ensure the safety of clinical applications of MSCs, thorough understanding of their impacts on tumor initiation and progression is essential. Here, to further explore the complex dialog between MSCs and tumor cells, umbilical cord-derived mesenchymal stem cells (UC-MSCs were employed to be cocultured with either breast or ovarian cancer cells. Though having no obvious influence on proliferation or apoptosis, UC-MSCs exerted intense stem cell-like properties promoting effects on both cancer models. Cocultured cancer cells showed enriched side population, enhanced sphere formation ability, and upregulated pluripotency-associated stem cell markers. Human cytokine array and real-time PCR revealed a panel of MSC-derived prostemness cytokines CCL2, CXCL1, IL-8, and IL-6 which were induced upon coculturing. We further revealed IL-1β, a well-characterized proinflammatory cytokine, to be the inducer of these prostemness cytokines, which was generated from inflammatory UC-MSCs in an autocrine manner. Additionally, with introduction of IL-1RA (an IL-1 receptor antagonist into the coculturing system, the stem cell-like characteristics promoting effects of inflammatory UC-MSCs were partially blocked. Taken together, these findings suggest that transduced inflammatory MSCs work as a major source of IL-1β in tumor microenvironment and initiate the formation of prostemness niche via regulating their secretome in an IL-1β-dependent manner.

  5. Platelets Drive Thrombus Propagation in a Hematocrit and Glycoprotein VI-Dependent Manner in an In Vitro Venous Thrombosis Model.

    Science.gov (United States)

    Lehmann, Marcus; Schoeman, Rogier M; Krohl, Patrick J; Wallbank, Alison M; Samaniuk, Joseph R; Jandrot-Perrus, Martine; Neeves, Keith B

    2018-05-01

    The objective of this study was to measure the role of platelets and red blood cells on thrombus propagation in an in vitro model of venous valvular stasis. A microfluidic model with dimensional similarity to human venous valves consists of a sinus distal to a sudden expansion, where for sufficiently high Reynolds numbers, 2 countercurrent vortices arise because of flow separation. The primary vortex is defined by the points of flow separation and reattachment. A secondary vortex forms in the deepest recess of the valve pocket characterized by low shear rates. An initial fibrin gel formed within the secondary vortex of a tissue factor-coated valve sinus. Platelets accumulated at the interface of the fibrin gel and the primary vortex. Red blood cells at physiological hematocrits were necessary to provide an adequate flux of platelets to support thrombus growth out of the valve sinus. A subpopulation of platelets that adhered to fibrin expose phosphatidylserine. Platelet-dependent thrombus growth was attenuated by inhibition of glycoprotein VI with a blocking Fab fragment or D-dimer. A 3-step process regulated by hemodynamics was necessary for robust thrombus propagation: First, immobilized tissue factor initiates coagulation and fibrin deposition within a low flow niche defined by a secondary vortex in the pocket of a model venous valve. Second, a primary vortex delivers platelets to the fibrin interface in a red blood cell-dependent manner. Third, platelets adhere to fibrin, activate through glycoprotein VI, express phosphatidylserine, and subsequently promote thrombus growth beyond the valve sinus and into the bulk flow. © 2018 American Heart Association, Inc.

  6. Seasonal variation in diurnal atmospheric grass pollen concentration profiles

    DEFF Research Database (Denmark)

    Peel, Robert George; Ørby, Pia Viuf; Skjøth, Carsten Ambelas

    2014-01-01

    the time of day when peak concentrations are most likely to occur using seasonally averaged diurnal profiles. Atmospheric pollen loads are highly dependent upon emissions, and different species of grass are known to flower and emit pollen at different times of the day and during different periods......In this study, the diurnal atmospheric grass pollen concentration profile within the Danish city of Aarhus was shown to change in a systematic manner as the pollen season progressed. Although diurnal grass pollen profiles can differ greatly from day-to-day, it is common practice to establish...... of the pollen season. Pollen concentrations are also influenced by meteorological factors - directly through those parameters that govern pollen dispersion and transport, and indirectly through the weather-driven flowering process. We found that three different profiles dominated the grass pollen season...

  7. Concentration dependence of the Huang scattering intensity of TaHsub(x) alloys

    International Nuclear Information System (INIS)

    Behr, H.; Metzger, H.; Peisl, J.

    1983-01-01

    The analysis of the concentration dependence of the Huang diffuse scattering intensity from ThHsub(x) single crystals has been re-evaluated using two quantities recently determined from independent measurements of the Bragg diffraction intensities. Good agreement between experiment and theory has been achieved. (author)

  8. Capturing student mathematical engagement through differently enacted classroom practices: applying a modification of Watson's analytical tool

    Science.gov (United States)

    Patahuddin, Sitti Maesuri; Puteri, Indira; Lowrie, Tom; Logan, Tracy; Rika, Baiq

    2018-04-01

    This study examined student mathematical engagement through the intended and enacted lessons taught by two teachers in two different middle schools in Indonesia. The intended lesson was developed using the ELPSA learning design to promote mathematical engagement. Based on the premise that students will react to the mathematical tasks in the forms of words and actions, the analysis focused on identifying the types of mathematical engagement promoted through the intended lesson and performed by students during the lesson. Using modified Watson's analytical tool (2007), students' engagement was captured from what the participants' did or said mathematically. We found that teachers' enacted practices had an influence on student mathematical engagement. The teacher who demonstrated content in explicit ways tended to limit the richness of the engagement; whereas the teacher who presented activities in an open-ended manner fostered engagement.

  9. Listeria monocytogenes alters mast cell phenotype, mediator and osteopontin secretion in a listeriolysin-dependent manner.

    Directory of Open Access Journals (Sweden)

    Catherine E Jobbings

    Full Text Available Whilst mast cells participate in the immune defence against the intracellular bacterium Listeria monocytogenes, there is conflicting evidence regarding the ability of L. monocytogenes to infect mast cells. It is known that the pore-forming toxin listeriolysin (LLO is important for mast cell activation, degranulation and the release of pro-inflammatory cytokines. Mast cells, however, are a potential source of a wide range of cytokines, chemokines and other mediators including osteopontin, which contributes to the clearing of L. monocytogenes infections in vivo, although its source is unknown. We therefore aimed to resolve the controversy of mast cell infection by L. monocytogenes and investigated the extent of mediator release in response to the bacterium. In this paper we show that the infection of bone marrow-derived mast cells by L. monocytogenes is inefficient and LLO-independent. LLO, however, is required for calcium-independent mast cell degranulation as well as for the transient and selective downregulation of cell surface CD117 (c-kit on mast cells. We demonstrate that in addition to the key pro-inflammatory cytokines TNF-α and IL-6, mast cells release a wide range of other mediators in response to L. monocytogenes. Osteopontin, IL-2, IL-4, IL-13 and granulocyte macrophage colony-stimulating factor (GM-CSF, and chemokines including CCL2, CCL3, CCL4 and CCL5 are released in a MyD88-dependent manner. The wide range of mediators released by mast cells in response to L. monocytogenes may play an important role in the recruitment and activation of a variety of immune cells in vivo. The cocktail of mediators, however, is unlikely to skew the immune response to a particular effector response. We propose that mast cells provide a hitherto unreported source of osteopontin, and may provide an important role in co-ordinating the immune response during Listeria infection.

  10. Mind Your Manners

    Energy Technology Data Exchange (ETDEWEB)

    Wiley, H. S.

    2010-01-01

    There has been a lot of talk in the media about the loss of courtesy in modern society. By many criteria, it seems that people in general have lost a degree of politeness. Reading some of the online comments after several recent articles in The Scientist would seem to indicate that biologists have also lost their manners. This lack of basic manners alarms me not only because of the obvious danger to our sense of community, but also because this type of behavior could damage society’s positive perception of scientists. Every time scientists (or anonymous bloggers posing as scientists) rant about the idiocy of someone who disagrees with them, our collective credibility erodes. Yes, there are a number of issues that we as scientists should be passionate about, but our objectives are best served by retaining an objective demeanor and respecting those to whom we happen to disagree.

  11. Dependence of radioprotective effect of chemical modifying agents on their intracellular concentrations

    International Nuclear Information System (INIS)

    Eidus, L.K.; Korystov, Y.N.; Kublik, L.N.; Vexler, A.M.

    1982-01-01

    Regularities of the radioprotective effect of chemical modifying agents cysteamine, caffeine benzoate, thioglycolic acid, and caffeine, all weak electrolytes, have been studied in cultured Chinese hamster cells. Efficiency of protection is shown to be dependent on pH and concentrations of the drug inside the cells and in the medium. Based on the theory of the dissociation of weak electrolytes and their distribution between the cells and the medium a strong correlation between the efficiency of modification of the radiation response and intracellular concentration of a modifying agent is shown. (author)

  12. Temperature-dependent transformation thermotics for unsteady states: Switchable concentrator for transient heat flow

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ying, E-mail: 13110290008@fudan.edu.cn [Department of Mechanics and Engineering Science, Fudan University, Shanghai 200433 (China); Shen, Xiangying, E-mail: 13110190068@fudan.edu.cn [Department of Physics, State Key Laboratory of Surface Physics, and Collaborative Innovation Center of Advanced Microstructures, Fudan University, Shanghai 200433 (China); Huang, Jiping, E-mail: jphuang@fudan.edu.cn [Department of Physics, State Key Laboratory of Surface Physics, and Collaborative Innovation Center of Advanced Microstructures, Fudan University, Shanghai 200433 (China); Ni, Yushan, E-mail: niyushan@fudan.edu.cn [Department of Mechanics and Engineering Science, Fudan University, Shanghai 200433 (China)

    2016-04-22

    For manipulating heat flow efficiently, recently we established a theory of temperature-dependent transformation thermotics which holds for steady-state cases. Here, we develop the theory to unsteady-state cases by considering the generalized Fourier's law for transient thermal conduction. As a result, we are allowed to propose a new class of intelligent thermal metamaterial — switchable concentrator, which is made of inhomogeneous anisotropic materials. When environmental temperature is below or above a critical value, the concentrator is automatically switched on, namely, it helps to focus heat flux in a specific region. However, the focusing does not affect the distribution pattern of temperature outside the concentrator. We also perform finite-element simulations to confirm the switching effect according to the effective medium theory by assembling homogeneous isotropic materials, which bring more convenience for experimental fabrication than inhomogeneous anisotropic materials. This work may help to figure out new intelligent thermal devices, which provide more flexibility in controlling heat flow, and it may also be useful in other fields that are sensitive to temperature gradient, such as the Seebeck effect. - Highlights: • Established the unsteady-state temperature dependent transformation thermotics. • A thermal concentrator with switchable functionality. • An effective-medium design for experimental realization.

  13. The adipokinetic hormone receptor modulates sexual behavior, pheromone perception and pheromone production in a sex-specific and starvation-dependent manner in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Sebastien eLebreton

    2016-01-01

    Full Text Available Food availability and nutritional status shape the reproductive activity of many animals. In rodents, hormones such as gonadotropin-releasing hormone (GnRH, restore energy homeostasis not only through regulating e.g. caloric intake and energy housekeeping, but also through modulating sex drive. We investigated whether the insect homologue of the GnRH receptor, the adipokinetic hormone receptor (AKHR modulates sexual behavior of the fruit fly Drosophila melanogaster depending on nutritional status. We found that AKHR regulates male, but not female sexual behavior in a starvation-dependent manner. Males lacking AKHR showed a severe decrease in their courtship activity when starved, as well as an increase in mating duration when fed. AKHR expression is particularly strong in the subesophageal zone (SEZ, Ito et al. 2014. We found axonal projections from AKHR-expressing neurons to higher brain centers including specific glomeruli in the antennal lobe. Among the glomeruli that received projections were those dedicated to detecting the male specific pheromone cis-vaccenyl acetate (cVA. Accordingly, responses to cVA were dependent on the nutritional status of flies. AKHR was also involved in the regulation of the production of cuticular pheromones, 7,11-heptacosadiene and 7-tricosene. This effect was observed only in females and depended on their feeding state. AKHR has therefore a dual role on both pheromone perception and production. For the first time our study shows an effect of AKHR on insect sexual behavior and physiology. Our results support the hypothesis of a conserved role of the GnRH/AKH pathway on a nutritional state-dependent regulation of reproduction in both vertebrates and invertebrates.

  14. Concentration Dependences of the Surface Tension and Density of Solutions of Acetone-Ethanol-Water Systems at 293 K

    Science.gov (United States)

    Dadashev, R. Kh.; Dzhambulatov, R. S.; Mezhidov, V. Kh.; Elimkhanov, D. Z.

    2018-05-01

    Concentration dependences of the surface tension and density of solutions of three-component acetone-ethanol-water systems and the bounding binary systems at 273 K are studied. The molar volume, adsorption, and composition of surface layers are calculated. Experimental data and calculations show that three-component solutions are close to ideal ones. The surface tensions of these solutions are calculated using semi-empirical and theoretical equations. Theoretical equations qualitatively convey the concentration dependence of surface tension. A semi-empirical method based on the Köhler equation allows us to predict the concentration dependence of surface tension within the experimental error.

  15. Communication: Modeling of concentration dependent water diffusivity in ionic solutions: Role of intermolecular charge transfer

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Yi; Berkowitz, Max L., E-mail: maxb@unc.edu, E-mail: ykanai@unc.edu; Kanai, Yosuke, E-mail: maxb@unc.edu, E-mail: ykanai@unc.edu [Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 (United States)

    2015-12-28

    The translational diffusivity of water in solutions of alkali halide salts depends on the identity of ions, exhibiting dramatically different behavior even in solutions of similar salts of NaCl and KCl. The water diffusion coefficient decreases as the salt concentration increases in NaCl. Yet, in KCl solution, it slightly increases and remains above bulk value as salt concentration increases. Previous classical molecular dynamics simulations have failed to describe this important behavior even when polarizable models were used. Here, we show that inclusion of dynamical charge transfer among water molecules produces results in a quantitative agreement with experiments. Our results indicate that the concentration-dependent diffusivity reflects the importance of many-body effects among the water molecules in aqueous ionic solutions. Comparison with quantum mechanical calculations shows that a heterogeneous and extended distribution of charges on water molecules around the ions due to ion-water and also water-water charge transfer plays a very important role in controlling water diffusivity. Explicit inclusion of the charge transfer allows us to model accurately the difference in the concentration-dependent water diffusivity between Na{sup +} and K{sup +} ions in simulations, and it is likely to impact modeling of a wide range of systems for medical and technological applications.

  16. Data-informed nudges for student engagement and success

    OpenAIRE

    Stephens, Jason; Leichtweis, Steve; Liu, Danny; Blumenstein, Marion; Richards, Deborah

    2018-01-01

    Student engagement has never mattered more in college and university education. While the problem of low engagement and underachievement may differ greatly depending on learning contexts their relationship is well-established. Increasingly, digital technologies have allowed teachers to utilize actionable insights gleaned from data about learner engagement and performance to influence students’ choices on regulating their learning behaviour towards academic success. In this context, we apply t...

  17. Oxidative stress mediated toxicity of TiO2 nanoparticles after a concentration and time dependent exposure of the aquatic macrophyte Hydrilla verticillata.

    Science.gov (United States)

    Spengler, Annette; Wanninger, Lena; Pflugmacher, Stephan

    2017-09-01

    The present study focused on oxidative stress effects in the aquatic macrophyte Hydrilla verticillata after exposure to titanium dioxide nanoparticles (TiO 2 -NPs). Experiments were conducted with different TiO 2 -NPs and concentrations (0.1 mg/L and 10 mg/L) in a time-dependent manner (0 h, 24 h, 48 h, 96 h, 168 h). To assess various levels of the oxidative stress response in H. verticillata, the level of hydrogen peroxide (H 2 O 2 ), the ratio of reduced to oxidized glutathione (GSH/GSSG), and activities of the antioxidative enzymes catalase (CAT) and glutathione reductase (GR) were evaluated. Study results imply oxidative stress effects after TiO 2 -NP exposure as adaptations in plant metabolism became apparent to counteract increased ROS formation. All TiO 2 -NPs caused elevated activities of the enzymes CAT and GR. Moreover, decreased ratios of GSH/GSSG indicated an activation of GSH-dependent pathways counteracting ROS formation. Plants exposed to a bulk-sized control revealed a size-dependent influence on the antioxidative stress response. As H 2 O 2 level increases were solely detected after exposure to 10 mg/L TiO 2 -NPs and nano-exposed plants showed normalization in its antioxidative stress response after 168h of exposure, it can be suggested that macrophytes are able to cope with currently predicted low-level exposures to TiO 2 -NPs. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Time, Concentration, and pH-Dependent Transport and Uptake of Anthocyanins in a Human Gastric Epithelial (NCI-N87 Cell Line

    Directory of Open Access Journals (Sweden)

    Allison A. Atnip

    2017-02-01

    Full Text Available Anthocyanins are the largest class of water soluble plant pigments and a common part of the human diet. They may have many potential health benefits, including antioxidant, anti-inflammatory, anti-cancer, and cardioprotective activities. However, anthocyanin metabolism is not well understood. Studies suggest that anthocyanins absorption may occur in the stomach, in which the acidic pH favors anthocyanin stability. A gastric epithelial cell line (NCI-N87 has been used to study the behavior of anthocyanins at a pH range of 3.0–7.4. This work examines the effects of time (0–3 h, concentration (50–1500 µM, and pH (3.0, 5.0, 7.4 on the transport and uptake of anthocyanins using NCI-N87 cells. Anthocyanins were transported from the apical to basolateral side of NCI-N87 cells in time and dose dependent manners. Over the treatment time of 3 h the rate of transport increased, especially with higher anthocyanin concentrations. The non-linear rate of transport may suggest an active mechanism for the transport of anthocyanins across the NCI-N87 monolayer. At apical pH 3.0, higher anthocyanin transport was observed compared to pH 5.0 and 7.4. Reduced transport of anthocyanins was found to occur at apical pH 5.0.

  19. Tetrahydrobiopterin Has a Glucose-Lowering Effect by Suppressing Hepatic Gluconeogenesis in an Endothelial Nitric Oxide Synthase–Dependent Manner in Diabetic Mice

    Science.gov (United States)

    Abudukadier, Abulizi; Fujita, Yoshihito; Obara, Akio; Ohashi, Akiko; Fukushima, Toru; Sato, Yuichi; Ogura, Masahito; Nakamura, Yasuhiko; Fujimoto, Shimpei; Hosokawa, Masaya; Hasegawa, Hiroyuki; Inagaki, Nobuya

    2013-01-01

    Endothelial nitric oxide synthase (eNOS) dysfunction induces insulin resistance and glucose intolerance. Tetrahydrobiopterin (BH4) is an essential cofactor of eNOS that regulates eNOS activity. In the diabetic state, BH4 is oxidized to 7,8-dihydrobiopterin, which leads to eNOS dysfunction owing to eNOS uncoupling. The current study investigates the effects of BH4 on glucose metabolism and insulin sensitivity in diabetic mice. Single administration of BH4 lowered fasting blood glucose levels in wild-type mice with streptozotocin (STZ)-induced diabetes and alleviated eNOS dysfunction by increasing eNOS dimerization in the liver of these mice. Liver has a critical role in glucose-lowering effects of BH4 through suppression of hepatic gluconeogenesis. BH4 activated AMP kinase (AMPK), and the suppressing effect of BH4 on gluconeogenesis was AMPK-dependent. In addition, the glucose-lowering effect and activation of AMPK by BH4 did not appear in mice with STZ-induced diabetes lacking eNOS. Consecutive administration of BH4 in ob/ob mice ameliorated glucose intolerance and insulin resistance. Taken together, BH4 suppresses hepatic gluconeogenesis in an eNOS-dependent manner, and BH4 has a glucose-lowering effect as well as an insulin-sensitizing effect in diabetic mice. BH4 has potential in the treatment of type 2 diabetes. PMID:23649519

  20. Light at night acutely impairs glucose tolerance in a time-, intensity- and wavelength-dependent manner in rats.

    Science.gov (United States)

    Opperhuizen, Anne-Loes; Stenvers, Dirk J; Jansen, Remi D; Foppen, Ewout; Fliers, Eric; Kalsbeek, Andries

    2017-07-01

    Exposure to light at night (LAN) has increased dramatically in recent decades. Animal studies have shown that chronic dim LAN induced obesity and glucose intolerance. Furthermore, several studies in humans have demonstrated that chronic exposure to artificial LAN may have adverse health effects with an increased risk of metabolic disorders, including type 2 diabetes. It is well-known that acute exposure to LAN affects biological clock function, hormone secretion and the activity of the autonomic nervous system, but data on the effects of LAN on glucose homeostasis are lacking. This study aimed to investigate the acute effects of LAN on glucose metabolism. Male Wistar rats were subjected to i.v. glucose or insulin tolerance tests while exposed to 2 h of LAN in the early or late dark phase. In subsequent experiments, different light intensities and wavelengths were used. LAN exposure early in the dark phase at ZT15 caused increased glucose responses during the first 20 min after glucose infusion (p light of 50 and 150 lx induced greater glucose responses than 5 and 20 lx, whereas all intensities other than 5 lx reduced locomotor activity. Green light induced glucose intolerance, but red and blue light did not, suggesting the involvement of a specific retina-brain pathway. Together, these data show that exposure to LAN has acute adverse effects on glucose metabolism in a time-, intensity- and wavelength-dependent manner.

  1. A novel technique to determine concentration-dependent solvent dispersion in Vapex

    Energy Technology Data Exchange (ETDEWEB)

    Abukhalifeh, H.; Lohi, A.; Upreti, S. R. [Department of Chemical Engineering, Ryerson University, 350 Victoria Street, Toronto, Ontario, M5B 2K3 (Canada)

    2009-07-01

    Vapex (vapor extraction of heavy oil and bitumen) is a promising recovery technology because it consumes low energy, and is very environmentally-friendly. The dispersion of solvents into heavy oil and bitumen is a crucial transport property governing Vapex. The accurate determination of solvent dispersion in Vapex is essential to effectively predict the amount and time scale of oil recovery as well to optimize the field operations. In this work, a novel technique is developed to experimentally determine the concentration-dependent dispersion coefficient of a solvent in Vapex process. The principles of variational calculus are utilized in conjunction with a mass transfer model of the experimental Vapex process. A computational algorithm is developed to optimally compute solvent dispersion as a function of its concentration in heavy oil. The developed technique is applied to Vapex utilizing propane as a solvent. The results show that dispersion of propane is a unimodal function of its concentration in bitumen. (author)

  2. A Novel Technique to Determine Concentration-Dependent Solvent Dispersion in Vapex

    Directory of Open Access Journals (Sweden)

    Hadil Abukhalifeh

    2009-10-01

    Full Text Available Vapex (vapor extraction of heavy oil and bitumen is a promising recovery technology because it consumes low energy, and is very environmentally-friendly. The dispersion of solvents into heavy oil and bitumen is a crucial transport property governing Vapex. The accurate determination of solvent dispersion in Vapex is essential to effectively predict the amount and time scale of oil recovery as well to optimize the field operations. In this work, a novel technique is developed to experimentally determine the concentration-dependent dispersion coefficient of a solvent in Vapex process. The principles of variational calculus are utilized in conjunction with a mass transfer model of the experimental Vapex process. A computational algorithm is developed to optimally compute solvent dispersion as a function of its concentration in heavy oil. The developed technique is applied to Vapex utilizing propane as a solvent. The results show that dispersion of propane is a unimodal function of its concentration in bitumen.

  3. Communication: Modeling electrolyte mixtures with concentration dependent dielectric permittivity

    Science.gov (United States)

    Chen, Hsieh; Panagiotopoulos, Athanassios Z.

    2018-01-01

    We report a new implicit-solvent simulation model for electrolyte mixtures based on the concept of concentration dependent dielectric permittivity. A combining rule is found to predict the dielectric permittivity of electrolyte mixtures based on the experimentally measured dielectric permittivity for pure electrolytes as well as the mole fractions of the electrolytes in mixtures. Using grand canonical Monte Carlo simulations, we demonstrate that this approach allows us to accurately reproduce the mean ionic activity coefficients of NaCl in NaCl-CaCl2 mixtures at ionic strengths up to I = 3M. These results are important for thermodynamic studies of geologically relevant brines and physiological fluids.

  4. Glucocorticoids inhibit the proliferation of IL-2-dependent T cell clones

    International Nuclear Information System (INIS)

    Fresno, M.; Redondo, J.M.; Lopez-Rivas, A.

    1986-01-01

    It has been shown that glucocorticoids inhibit mitogen or antigen-induced lymphocyte proliferation by decreasing the production of interleukin-2 (IL-2). They have studied the effect of dexamethasone (Dx) on the proliferation of IL-2-dependent T cell clones. They have found that preincubation of these clones with Dx inhibits ( 3 H) thymidine incorporation and cell proliferation in a dose-dependent manner (ID 50 % 5 x 10 -10 M). The inhibition of DNA synthesis by Dx was dependent on the concentration of IL-2. High concentration of IL-2 reversed completely this inhibition. The action of Dx seems to be mediated through the induction of a protein since the simultaneous presence of cycloheximide and Dx prevented the inhibitory effect of the latter. Moreover, dialyzed conditioned medium of Dx treated cells inhibited DNA synthesis by T cell clones. The biochemical characterization of this protein is in progress

  5. Overexpression of Endogenous Anti-Oxidants with Selenium Supplementation Protects Trophoblast Cells from Reactive Oxygen Species-Induced Apoptosis in a Bcl-2-Dependent Manner.

    Science.gov (United States)

    Khera, Alisha; Vanderlelie, Jessica J; Holland, Olivia; Perkins, Anthony V

    2017-06-01

    The human placenta provides life support for the developing foetus, and a healthy placenta is a prerequisite to a healthy start to life. Placental tissue is subject to oxidative stress which can lead to pathological conditions of pregnancy such as preeclampsia, preterm labour and intrauterine growth restriction. Up-regulation of endogenous anti-oxidants may alleviate placental oxidative stress and provide a therapy for these complications of pregnancy. In this study, selenium supplementation, as inorganic sodium selenite (NaSel) or organic selenomethionine (SeMet), was used to increase the protein production and cellular activity of the important redox active proteins glutathione peroxidase (GPx) and thioredoxin reductase (Thx-Red). Placental trophoblast cell lines, BeWo, JEG-3 and Swan-71, were cultured in various concentrations of NaSel or SeMet for 24 h and cell extracts prepared for western blots and enzyme assays. Rotenone and antimycin were used to stimulate mitochondrial reactive oxygen species (ROS) production and induce apoptosis. Trophoblast cells supplemented with 100 nM NaSel and 500 nM SeMet exhibited significantly enhanced expression and activity of both GPx and Thx-Red. Antimycin and rotenone were found to generate ROS when measured by 2',7'-dichlorofluorescein diacetate (DCFDA) assay, and selenium supplementation was shown to reduce ROS production in a dose-dependent manner. Rotenone, 100 μM treatment for 4 h, caused trophoblast cell apoptosis as evidenced by increased Annexin V binding and decreased expression of Bcl-2. In both assays of apoptosis, selenium supplementation was able to prevent apoptosis, preserve Bcl-2 expression and protect trophoblast cells from mitochondrial oxidative stress. This data suggests that selenoproteins such as GPx and Thx-Red have an important role in protecting trophoblast cells from mitochondrial oxidative stress and that selenium supplementation may be important in treating some placental pathologies.

  6. Concentration dependence of fluorine impurity spin-lattice relaxation rate in bone mineral

    International Nuclear Information System (INIS)

    Code, R.F.; Armstrong, R.L.; Cheng, P.-T.

    1992-01-01

    The concentration dependence of the fluoride ion spin-lattice relaxation rate has been observed by nuclear magnetic resonance experiments on samples of defatted and dried bone. The 19 F spin-lattice relaxation rates increased linearly with bone fluoride concentration. Different results were obtained from trabecular than from cortical bone. For the same macroscopic fluoride content per gram of bone calcium, relaxation rate is significantly faster in cortical bone. Relaxation rates in cortical bone samples prepared from rats and dogs were apparently controlled by the same species-independent processes. For samples from beagle dogs, bulk fluoride concentrations measured by neutron activation analysis were 3.1±0.3 times greater in trabecular bone than in corresponding cortical bone. The beagle spin-lattice relaxation data suggest that microscopic fluoride concentrations in bone mineral were 1.8±0.4 times greater in trabecular bone than in cortical bone. It is concluded that accumulation of fluoride impurities in bone mineral is non-uniform. (author)

  7. The Complete Solution of Fick's Second Law of Diffusion with Time-dependent Diffusion Coefficient and Surface Concentration

    DEFF Research Database (Denmark)

    Mejlbro, Leif

    1996-01-01

    Fick's Second Law of Diffusion with time-dependent diffusioncoefficient and surface concentration is solved. Mimicking the classicalsolution, special time-dependent surface concentration functions areconsidered. These models are used in giving estimates of the lifetimeof the structure, when...... the concrete cover is given, as well as estimatesof the thickness of the concrete cover, when the expected lifetime is given.*Note: Book tilte: Durability of Concrete in Saline Environment...

  8. Late engagement of CD86 after influenza virus clearance promotes recovery in a FoxP3+ regulatory T cell dependent manner.

    Directory of Open Access Journals (Sweden)

    Emily K Moser

    2014-08-01

    Full Text Available Influenza A virus (IAV infection in the respiratory tract triggers robust innate and adaptive immune responses, resulting in both virus clearance and lung inflammation and injury. After virus clearance, resolution of ongoing inflammation and tissue repair occur during a distinct recovery period. B7 family co-stimulatory molecules such as CD80 and CD86 have important roles in modulating T cell activity during the initiation and effector stages of the host response to IAV infection, but their potential role during recovery and resolution of inflammation is unknown. We found that antibody-mediated CD86 blockade in vivo after virus clearance led to a delay in recovery, characterized by increased numbers of lung neutrophils and inflammatory cytokines in airways and lung interstitium, but no change in conventional IAV-specific T cell responses. However, CD86 blockade led to decreased numbers of FoxP3+ regulatory T cells (Tregs, and adoptive transfer of Tregs into αCD86 treated mice rescued the effect of the blockade, supporting a role for Tregs in promoting recovery after virus clearance. Specific depletion of Tregs late after infection mimicked the CD86 blockade phenotype, confirming a role for Tregs during recovery after virus clearance. Furthermore, we identified neutrophils as a target of Treg suppression since neutrophil depletion in Treg-depleted mice reduced excess inflammatory cytokines in the airways. These results demonstrate that Tregs, in a CD86 dependent mechanism, contribute to the resolution of disease after IAV infection, in part by suppressing neutrophil-driven cytokine release into the airways.

  9. Reduced plasma aldosterone concentrations in randomly selected patients with insulin-dependent diabetes mellitus.

    LENUS (Irish Health Repository)

    Cronin, C C

    2012-02-03

    Abnormalities of the renin-angiotensin system have been reported in patients with diabetes mellitus and with diabetic complications. In this study, plasma concentrations of prorenin, renin, and aldosterone were measured in a stratified random sample of 110 insulin-dependent (Type 1) diabetic patients attending our outpatient clinic. Fifty-four age- and sex-matched control subjects were also examined. Plasma prorenin concentration was higher in patients without complications than in control subjects when upright (geometric mean (95% confidence intervals (CI): 75.9 (55.0-105.6) vs 45.1 (31.6-64.3) mU I-1, p < 0.05). There was no difference in plasma prorenin concentration between patients without and with microalbuminuria and between patients without and with background retinopathy. Plasma renin concentration, both when supine and upright, was similar in control subjects, in patients without complications, and in patients with varying degrees of diabetic microangiopathy. Plasma aldosterone was suppressed in patients without complications in comparison to control subjects (74 (58-95) vs 167 (140-199) ng I-1, p < 0.001) and was also suppressed in patients with microvascular disease. Plasma potassium was significantly higher in patients than in control subjects (mean +\\/- standard deviation: 4.10 +\\/- 0.36 vs 3.89 +\\/- 0.26 mmol I-1; p < 0.001) and plasma sodium was significantly lower (138 +\\/- 4 vs 140 +\\/- 2 mmol I-1; p < 0.001). We conclude that plasma prorenin is not a useful early marker for diabetic microvascular disease. Despite apparently normal plasma renin concentrations, plasma aldosterone is suppressed in insulin-dependent diabetic patients.

  10. Indoor visible mold and mold odor are associated with new-onset childhood wheeze in a dose-dependent manner.

    Science.gov (United States)

    Shorter, Caroline; Crane, Julian; Pierse, Nevil; Barnes, Phillipa; Kang, Janice; Wickens, Kristin; Douwes, Jeroen; Stanley, Thorsten; Täubel, Martin; Hyvärinen, Anne; Howden-Chapman, Philippa

    2018-01-01

    Evidence is accumulating that indoor dampness and mold are associated with the development of asthma. The underlying mechanisms remain unknown. New Zealand has high rates of both asthma and indoor mold and is ideally placed to investigate this. We conducted an incident case-control study involving 150 children with new-onset wheeze, aged between 1 and 7 years, each matched to two control children with no history of wheezing. Each participant's home was assessed for moisture damage, condensation, and mold growth by researchers, an independent building assessor and parents. Repeated measures of temperature and humidity were made, and electrostatic dust cloths were used to collect airborne microbes. Cloths were analyzed using qPCR. Children were skin prick tested for aeroallergens to establish atopy. Strong positive associations were found between observations of visible mold and new-onset wheezing in children (adjusted odds ratios ranged between 1.30 and 3.56; P ≤ .05). Visible mold and mold odor were consistently associated with new-onset wheezing in a dose-dependent manner. Measurements of qPCR microbial levels, temperature, and humidity were not associated with new-onset wheezing. The association between mold and new-onset wheeze was not modified by atopic status, suggesting a non-allergic association. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. An Exploration Of Engagement, Motiviation And Student-Centered Learning In Physical Education

    Directory of Open Access Journals (Sweden)

    Barbara WARNER

    2015-12-01

    Full Text Available This author examines the discrepancy between the known benefits of physical activity and the startling statistics of obesity in children between the ages of 12 and 17. She queries if it is time to look at educators as contributing to this problem and questions if our current teaching styles and curriculum are working for students. In addition, the author explores the question if by allowing our students autonomy, will this equate to engagement and motivation to continue to participate in physical activities? Through a discussion of her personal experiences and a literature review focusing on the areas of autonomy, engagement and motivation, the author shares input into how and why some students experience physical education in a negative manner, and some things that educators can do to improve student engagement and motivation. Her argument demonstrates that an autonomous, student-centered teaching approach will positively affect student engagement, which in turn causes motivation and a desire to participate in life-long physical activity.

  12. Revenue Sources and Social Media Engagement Among Environmentally Focused Nonprofits

    Directory of Open Access Journals (Sweden)

    John R. McCaskill

    2017-12-01

    Full Text Available This study examines social media efforts among environmentally focused nonprofits. A survey of environmentally focused nonprofits revealed that more than half of these organizations receive government funding. Prior research demonstrates social media is an efficient medium in which to simultaneously communicate with multiple stakeholders. However, stakeholder engagement is likely tied with the need to raise funds. From that basis, we discuss social media use among nonprofits and develop hypotheses about differences in social media use among organizations receiving government funds and those not receiving government funds. Our hypotheses are rooted in resource dependency theory (RDT and dialogic communication theory (DCT. We test our hypotheses on data from environmentally focused nonprofits by comparing the levels of social media engagement with varying levels of their total funding provided by government grants to determine if there is a correlation with the level of public engagement via social media. We find the level of engagement on the social media site Facebook is lower for government-funded environmental nonprofits than privately funded ones. The findings of reduced social media engagement and the dependence upon government funding versus private funding supports the precepts of resource dependency theory.

  13. Size-dependent concentration of N0 paramagnetic centres in HPHT nanodiamonds

    OpenAIRE

    Yavkin, Boris V; Mamin, Georgy V; Gafurov, Marat R.; Orlinskii, Sergei B.

    2015-01-01

    Size-calibrated commercial nanodiamonds synthesized by high-pressure high-temperature (HPHT) technique were studied by high-frequency W and conventional X band electron paramagnetic resonance (EPR) spectroscopy. The numbers of spins in the studied samples were estimated. The core-shell model of the HPHT nanodiamonds was proposed to explain the observed dependence of the concentration of the N0 paramagnetic centers. Two other observed paramagnetic centers are attributed to the two types of str...

  14. Caffeine dependence in rats: effects of exposure duration and concentration.

    Science.gov (United States)

    Dingle, Rachel N; Dreumont-Boudreau, Sarah E; Lolordo, Vincent M

    2008-09-03

    Groups of rats were chronically exposed to a 1.0-g/L caffeine solution for 5, 10, 15 or 20 days. Upon removal of caffeine, rats were given brief exposure to a novel flavour CS (withdrawal CS) followed by 12 days of plain water and then brief exposure to a second flavour CS (neutral CS). Only rats exposed to 20 days of caffeine strongly preferred the neutral CS to the withdrawal CS in a 2-bottle test. In Experiment 2, groups of rats were chronically exposed to caffeine at one of four concentrations (1.0, 0.5, 0.25, or 0.125 g/L) for 21 days, after which withdrawal and neutral CSs were established. Only rats that drank the highest caffeine concentration, 1.0 g/L, preferred the neutral CS to the withdrawal CS. This suggests that long exposure to a strong caffeine solution is required in order to induce dependence in rats such that a CS associated with the withdrawal of caffeine becomes avoided.

  15. Glymphatic clearance controls state-dependent changes in brain lactate concentration.

    Science.gov (United States)

    Lundgaard, Iben; Lu, Minh Lon; Yang, Ezra; Peng, Weiguo; Mestre, Humberto; Hitomi, Emi; Deane, Rashid; Nedergaard, Maiken

    2017-06-01

    Brain lactate concentration is higher during wakefulness than in sleep. However, it is unknown why arousal is linked to an increase in brain lactate and why lactate declines within minutes of sleep. Here, we show that the glymphatic system is responsible for state-dependent changes in brain lactate concentration. Suppression of glymphatic function via acetazolamide treatment, cisterna magna puncture, aquaporin 4 deletion, or changes in body position reduced the decline in brain lactate normally observed when awake mice transition into sleep or anesthesia. Concurrently, the same manipulations diminished accumulation of lactate in cervical, but not in inguinal lymph nodes when mice were anesthetized. Thus, our study suggests that brain lactate is an excellent biomarker of the sleep-wake cycle and increases further during sleep deprivation, because brain lactate is inversely correlated with glymphatic-lymphatic clearance. This analysis provides fundamental new insight into brain energy metabolism by demonstrating that glucose that is not fully oxidized can be exported as lactate via glymphatic-lymphatic fluid transport.

  16. Acetylation and glycation of fibrinogen in vitro occur at specific lysine residues in a concentration dependent manner: A mass spectrometric and isotope labeling study

    International Nuclear Information System (INIS)

    Svensson, Jan; Bergman, Ann-Charlotte; Adamson, Ulf; Blombäck, Margareta; Wallén, Håkan; Jörneskog, Gun

    2012-01-01

    Highlights: ► Fibrinogen was incubated in vitro with glucose or aspirin. ► Acetylations and glycations were found at twelve lysine sites by mass spectrometry. ► The labeling by aspirin and glucose occurred dose-dependently. ► No competition between glucose and aspirin for binding to fibrinogen was found. -- Abstract: Aspirin may exert part of its antithrombotic effects through platelet-independent mechanisms. Diabetes is a condition in which the beneficial effects of aspirin are less prominent or absent – a phenomenon called “aspirin resistance”. We investigated whether acetylation and glycation occur at specific sites in fibrinogen and if competition between glucose and aspirin in binding to fibrinogen occurs. Our hypothesis was that such competition might be one explanation to “aspirin resistance” in diabetes. After incubation of fibrinogen in vitro with aspirin (0.8 mM, 24 h) or glucose (100 mM, 5–10 days), we found 12 modified sites with mass spectrometric techniques. Acetylations in the α-chain: αK191, αK208, αK224, αK429, αK457, αK539, αK562, in the β-chain: βK233, and in the γ-chain: γK170 and γK273. Glycations were found at βK133 and γK75, alternatively γK85. Notably, the lysine 539 is a site involved in FXIII-mediated cross-linking of fibrin. With isotope labeling in vitro, using [ 14 C-acetyl]salicylic acid and [ 14 C]glucose, a labeling of 0.013–0.084 and 0.12–0.5 mol of acetylated and glycated adduct/mol fibrinogen, respectively, was found for clinically (12.9–100 μM aspirin) and physiologically (2–8 mM glucose) relevant plasma concentrations. No competition between acetylation and glycation could be demonstrated. Thus, fibrinogen is acetylated at several lysine residues, some of which are involved in the cross-linking of fibrinogen. This may mechanistically explain why aspirin facilitates fibrin degradation. We find no support for the idea that glycation of fibrin(ogen) interferes with acetylation of

  17. Acetylation and glycation of fibrinogen in vitro occur at specific lysine residues in a concentration dependent manner: A mass spectrometric and isotope labeling study

    Energy Technology Data Exchange (ETDEWEB)

    Svensson, Jan, E-mail: jan.svensson@ki.se [Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital (Solna), SE-171 76 Stockholm (Sweden); Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, SE-182 88 Stockholm (Sweden); Bergman, Ann-Charlotte [Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital (Solna), SE-171 76 Stockholm (Sweden); Adamson, Ulf [Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, SE-182 88 Stockholm (Sweden); Blombaeck, Margareta [Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital (Solna), SE-171 76 Stockholm (Sweden); Wallen, Hakan; Joerneskog, Gun [Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, SE-182 88 Stockholm (Sweden)

    2012-05-04

    Highlights: Black-Right-Pointing-Pointer Fibrinogen was incubated in vitro with glucose or aspirin. Black-Right-Pointing-Pointer Acetylations and glycations were found at twelve lysine sites by mass spectrometry. Black-Right-Pointing-Pointer The labeling by aspirin and glucose occurred dose-dependently. Black-Right-Pointing-Pointer No competition between glucose and aspirin for binding to fibrinogen was found. -- Abstract: Aspirin may exert part of its antithrombotic effects through platelet-independent mechanisms. Diabetes is a condition in which the beneficial effects of aspirin are less prominent or absent - a phenomenon called 'aspirin resistance'. We investigated whether acetylation and glycation occur at specific sites in fibrinogen and if competition between glucose and aspirin in binding to fibrinogen occurs. Our hypothesis was that such competition might be one explanation to 'aspirin resistance' in diabetes. After incubation of fibrinogen in vitro with aspirin (0.8 mM, 24 h) or glucose (100 mM, 5-10 days), we found 12 modified sites with mass spectrometric techniques. Acetylations in the {alpha}-chain: {alpha}K191, {alpha}K208, {alpha}K224, {alpha}K429, {alpha}K457, {alpha}K539, {alpha}K562, in the {beta}-chain: {beta}K233, and in the {gamma}-chain: {gamma}K170 and {gamma}K273. Glycations were found at {beta}K133 and {gamma}K75, alternatively {gamma}K85. Notably, the lysine 539 is a site involved in FXIII-mediated cross-linking of fibrin. With isotope labeling in vitro, using [{sup 14}C-acetyl]salicylic acid and [{sup 14}C]glucose, a labeling of 0.013-0.084 and 0.12-0.5 mol of acetylated and glycated adduct/mol fibrinogen, respectively, was found for clinically (12.9-100 {mu}M aspirin) and physiologically (2-8 mM glucose) relevant plasma concentrations. No competition between acetylation and glycation could be demonstrated. Thus, fibrinogen is acetylated at several lysine residues, some of which are involved in the cross-linking of

  18. Concentration dependent transcriptome responses of zebrafish embryos after exposure to cadmium, cobalt and copper.

    Science.gov (United States)

    Sonnack, Laura; Klawonn, Thorsten; Kriehuber, Ralf; Hollert, Henner; Schäfers, Christoph; Fenske, Martina

    2017-12-01

    Environmental metals are known to cause harmful effects to fish of which many molecular mechanisms still require elucidation. Particularly concentration dependence of gene expression effects is unclear. Focusing on this matter, zebrafish embryo toxicity tests were used in combination with transcriptomics. Embryos were exposed to three concentrations of copper (CuSO 4 ), cadmium (CdCl 2 ) and cobalt (CoSO 4 ) from just after fertilization until the end of the 48hpf pre- and 96hpf post-hatch stage. The RNA was then analyzed on Agilent's Zebrafish (V3, 4×44K) arrays. Enrichment for GO terms of biological processes illustrated for cadmium that most affected GO terms were represented in all three concentrations, while for cobalt and copper most GO terms were represented in the lowest test concentration only. This suggested a different response to the non-essential cadmium than cobalt and copper. In cobalt and copper treated embryos, many developmental and cellular processes as well as the Wnt and Notch signaling pathways, were found significantly enriched. Also, different exposure concentrations affected varied functional networks. In contrast, the largest clusters of enriched GO terms for all three concentrations of cadmium included responses to cadmium ion, metal ion, xenobiotic stimulus, stress and chemicals. However, concentration dependence of mRNA levels was evident for several genes in all metal exposures. Some of these genes may be indicative of the mechanisms of action of the individual metals in zebrafish embryos. Real-time quantitative RT-PCR (qRT-PCR) verified the microarray data for mmp9, mt2, cldnb and nkx2.2a. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Measurements of the size dependence of the concentration of nonvolatile material in fog droplets

    Science.gov (United States)

    Ogren, J. A.; Noone, K. J.; Hallberg, A.; Heintzenberg, J.; Schell, D.; Berner, A.; Solly, I.; Kruisz, C.; Reischl, G.; Arends, B. G.; Wobrock, W.

    1992-11-01

    Measurements of the size dependence of the mass concentration of nonvolatile material dissolved and suspended in fog droplets were obtained with three complementary approaches, covering a size range from c. 1 50µm diameter: a counterflow virtual impactor, an eight-stage aerosol impactor, and a two-stage fogwater impactor. Concentrations were observed to decrease with size over the entire range, contrary to expectations of increasing concentrations at larger sizes. It is possible that the larger droplets had solute concentrations that increased with increasing size, but that the increase was too weak for the measurements to resolve. Future studies should consider the hypothesis that the droplets were coated with a surface-active substance that hindered their uptake of water.

  20. Bilirubin Modulates Acetylcholine Receptors In Rat Superior Cervical Ganglionic Neurons In a Bidirectional Manner

    Science.gov (United States)

    Zhang, Chengmi; Wang, Zhenmeng; Dong, Jing; Pan, Ruirui; Qiu, Haibo; Zhang, Jinmin; Zhang, Peng; Zheng, Jijian; Yu, Weifeng

    2014-01-01

    Autonomic dysfunction as a partial contributing factor to cardiovascular instability in jaundiced patients is often associated with increased serum bilirubin levels. Whether increased serum bilirubin levels could directly inhibit sympathetic ganglion transmission by blocking neuronal nicotinic acetylcholine receptors (nAChRs) remains to be elucidated. Conventional patch-clamp recordings were used to study the effect of bilirubin on nAChRs currents from enzymatically dissociated rat superior cervical ganglia (SCG) neurons. The results showed that low concnetrations (0.5 and 2 μM) of bilirubin enhanced the peak ACh-evoked currents, while high concentrations (3 to 5.5 µM) of bilirubin suppressed the currents with an IC50 of 4 ± 0.5 μM. In addition, bilirubin decreased the extent of desensitization of nAChRs in a concentration-dependent manner. This inhibitory effect of bilirubin on nAChRs channel currents was non-competitive and voltage independent. Bilirubin partly improved the inhibitory effect of forskolin on ACh-induced currents without affecting the action of H-89. These data suggest that the dual effects of enhancement and suppression of bilirubin on nAChR function may be ascribed to the action mechanism of positive allosteric modulation and direct blockade. Thus, suppression of sympathetic ganglionic transmission through postganglionic nAChRs inhibition may partially contribute to the adverse cardiovascular effects in jaundiced patients. PMID:25503810

  1. PICK1 regulates the trafficking of ASIC1a and acidotoxicity in a BAR domain lipid binding-dependent manner

    Directory of Open Access Journals (Sweden)

    Jin Wenying

    2010-12-01

    Full Text Available Abstract Background Acid-sensing ion channel 1a (ASIC1a is the major ASIC subunit determining acid-activated currents in brain neurons. Recent studies show that ASIC1a play critical roles in acid-induced cell toxicity. While these studies raise the importance of ASIC1a in diseases, mechanisms for ASIC1a trafficking are not well understood. Interestingly, ASIC1a interacts with PICK1 (protein interacting with C-kinase 1, an intracellular protein that regulates trafficking of several membrane proteins. However, whether PICK1 regulates ASIC1a surface expression remains unknown. Results Here, we show that PICK1 overexpression increases ASIC1a surface level. A BAR domain mutant of PICK1, which impairs its lipid binding capability, blocks this increase. Lipid binding of PICK1 is also required for PICK1-induced clustering of ASIC1a. Consistent with the effect on ASIC1a surface levels, PICK1 increases ASIC1a-mediated acidotoxicity and this effect requires both the PDZ and BAR domains of PICK1. Conclusions Taken together, our results indicate that PICK1 regulates trafficking and function of ASIC1a in a lipid binding-dependent manner.

  2. Concentration-dependent multiple chirality transition in halogen-bond-driven 2D self-assembly process

    Science.gov (United States)

    Miao, Xinrui; Li, Jinxing; Zha, Bao; Miao, Kai; Dong, Meiqiu; Wu, Juntian; Deng, Wenli

    2018-03-01

    The concentration-dependent self-assembly of iodine substituted thienophenanthrene derivative (5,10-DITD) is investigated at the 1-octanic acid/graphite interface using scanning tunneling microscopy. Three kinds of chiral arrangement and transition of 2D molecular assembly mainly driven by halogen bonding is clearly revealed. At high concentration the molecules self-assembled into a honeycomb-like chiral network. Except for the interchain van der Waals forces, this pattern is stabilized by intermolecular continuous Cdbnd O⋯I⋯S halogen bonds in each zigzag line. At moderate concentration, a chiral kite-like nanoarchitecture are observed, in which the Cdbnd O⋯I⋯S and I⋯Odbnd C halogen bonds, along with the molecule-solvent Cdbnd O⋯I⋯H halogen bonds are the dominated forces to determine the structural formation. At low concentration, the molecules form a chiral cyclic network resulting from the solvent coadsorption mainly by molecule-molecule Cdbnd O⋯I⋯S halogen bonds and molecule-solvent Cdbnd O⋯I⋯H halogen bonds. The density of molecular packing becomes lower with the decreasing of the solution concentration. The solution-concentration dependent self-assembly of thienophenanthrene derivative with iodine and ester chain moieties reveals that the type of intermolecular halogen bond and the number of the co-adsorbing 1-octanic acids by molecule-solvent Cdbnd O⋯I⋯H halogen bonds determine the formation and transformation of chirality. This research emphasizes the role of different types of halogen (I) bonds in the controllable supramolecular structures and provides an approach for the fabrication of chirality.

  3. A NodD-like protein activates transcription of genes involved with naringenin degradation in a flavonoid-dependent manner in Herbaspirillum seropedicae.

    Science.gov (United States)

    Wassem, R; Marin, A M; Daddaoua, A; Monteiro, R A; Chubatsu, L S; Ramos, J L; Deakin, W J; Broughton, W J; Pedrosa, F O; Souza, E M

    2017-03-01

    Herbaspirillum seropedicae is an associative, endophytic non-nodulating diazotrophic bacterium that colonises several grasses. An ORF encoding a LysR-type transcriptional regulator, very similar to NodD proteins of rhizobia, was identified in its genome. This nodD-like gene, named fdeR, is divergently transcribed from an operon encoding enzymes involved in flavonoid degradation (fde operon). Apigenin, chrysin, luteolin and naringenin strongly induce transcription of the fde operon, but not that of the fdeR, in an FdeR-dependent manner. The intergenic region between fdeR and fdeA contains several generic LysR consensus sequences (T-N 11 -A) and we propose a binding site for FdeR, which is conserved in other bacteria. DNase I foot-printing revealed that the interaction with the FdeR binding site is modified by the four flavonoids that stimulate transcription of the fde operon. Moreover, FdeR binds naringenin and chrysin as shown by isothermal titration calorimetry. Interestingly, FdeR also binds in vitro to the nod-box from the nodABC operon of Rhizobium sp. NGR234 and is able to activate its transcription in vivo. These results show that FdeR exhibits two features of rhizobial NodD proteins: nod-box recognition and flavonoid-dependent transcription activation, but its role in H. seropedicae and related organisms seems to have evolved to control flavonoid metabolism. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  4. Dependence of the concentrations of "1"3"7Cs and potassium in extracted soil solutions on soil humidity before centrifugation

    International Nuclear Information System (INIS)

    Prorok, V.V.; Datsenko, O.Yi.; Bulavyin, L.A.; Zlens'kij, S.Je.; Melnichenko, L.Yu.; Rozuvan, S.G.; Poperenko, L.V.; White, P.J.

    2017-01-01

    Concentrations of 137Cs and potassium in solutions extracted by centrifugation from soils selected at some experimental sites in the 10-km Exclusion Zone of Chornobyl Nuclear Plant were determined. The results showed that for the majority of investigated soils, the concentration of 137Cs in soil solution depends on the humidity of the soil before centrifugation. It is possible to explain the dependence of the concentration of 137Cs in the soil solution on soil humidity from the dependence of the concentrations of molecules of different molecular-gravimetric fractions in soil solution on soil humidity. Considerable amount of 137Cs in soil solution is associated with these molecules, that is why the concentration of 137Cs in the extracted soil solution changes with the humidity of soil. These dependences differ between soils. For the majority of investigated soils the concentration of 137Cs in the extracted soil solution increases with increasing humidity of the soil. By contrast, soil humidity had no effect on the potassium concentration in the extracted soil solution for any soil investigated. It is concluded, that potassium is practically not associated with molecules of different molecular-gravimetric fractions in the extracted soil solutions

  5. Isoproterenol Increases RANKL Expression in a ATF4/NFATc1-Dependent Manner in Mouse Osteoblastic Cells

    Directory of Open Access Journals (Sweden)

    Kyunghwa Baek

    2017-10-01

    Full Text Available Sympathetic nervous system stimulation-induced β-adrenergic signal transduction is known to induce bone loss and increase of osteoclast activity. Although isoproterenol, a nonspecific β-adrenergic receptor agonist, has been shown to increase receptor activator of NF-κB ligand (RANKL, the details of the regulatory mechanisms remain unclear. In the present study, we investigated the role of the nuclear factor of activated T-cells (NFAT in isoproterenol-induced RANKL expression in C2C12 and in primary cultured mouse calvarial cells. Isoproterenol increased nuclear factor of activated T-cells cytoplasmic 1 (NFATc1 and RANKL expressions at both mRNA and protein levels and increased NFAT reporter activity. NFATc1 knockdown blocked isoproterenol-mediated RANKL expression. Isoproterenol also promoted cAMP response element-binding protein 1 (CREB1 and activating transcription factor 4 (ATF4 phosphorylation. Isoproterenol-mediated transcriptional activation of NFAT was blocked by protein kinase A (PKA inhibitor H89. Isoproterenol-induced CREB1, ATF4, NFATc1, and RANKL expressions were suppressed by H89. Mutations in cAMP response element-like or NFAT-binding element suppressed isoproterenol-induced RANKL promoter activity. Chromatin immunoprecipitation analysis demonstrated that isoproterenol increased NFAT-binding and ATF4-binding activities on the mouse RANKL promoter, but did not increase CREB1-binding activity. Association of NFATc1 and ATF4 was not observed in a co-immunoprecipitation study. ATF4 knockdown suppressed isoproterenol-induced NFAT binding to the RANKL promoter, whereas NFATc1 knockdown did not suppress isoproterenol-induced ATF4 binding to the RANKL promoter. ATF4 knockdown suppressed isoproterenol-induced expressions of NFATc1 and RANKL. These results suggest that isoproterenol increases RANKL expression in an ATF4/NFATc1-dependent manner.

  6. Dependence of spleen sequestration on erythrocytes following administration of various concentrations of BMHP-197Hg

    International Nuclear Information System (INIS)

    Kapff, S. v.

    1980-01-01

    In the course of routine splenic scintiscanning, the effects of BMHP-Hg 197 concentrations on the kinetics of damaged erythrocytes and on image quality have been investigated. The following findings were obtained: 1. Significant displacement of the Price-Jones curve in dependence of BMHP concentrations. 2. No significant enzymatic changes 3. An enhanced labelling index at high concentrations and a higher spleen sequestration rate 4. A significant improvement of scintiscan quality at higher concentrations 5. Erythrocyte washing before incubation with BMHP was unnecessary as it does not improve the results to an extent that would warrant the tedious procedure. (orig.) [de

  7. Cord blood-derived macrophage-lineage cells rapidly stimulate osteoblastic maturation in mesenchymal stem cells in a glycoprotein-130 dependent manner.

    Directory of Open Access Journals (Sweden)

    Tania J Fernandes

    , including osteoclasts but not classically activated macrophages, can strongly drive MSC-osteoblastic commitment in OSM-dependent manner. This supports the notion that eliciting gp130-dependent signals in human MSC would be a useful approach to increase bone formation.

  8. Russia’s 2015 BRICS Presidency: Models of Engagement with International Organizations

    Directory of Open Access Journals (Sweden)

    Marina Larionova

    2016-09-01

    Full Text Available Six years after the first 2009 summit in Yekaterinburg, the BRICS grouping of Brazil, Russia, India, China and South Africa has established its identity as an informal global governance forum. The members have consistently consolidated their cooperation, expanded and deepened their agenda, coordinated efforts aimed at the recovery and growth of their economies, and engaged with other international organizations. This work continued during the Russian presidency in 2015. This article focuses on one dimension of BRICS performance: its engagement with international organizations. Atleast three reasons define the relevance of this analysis. First, since its launch the BRICS members collectively committed tobuilding a multipolar, fair and democratic world order, which would not be possible without cooperating with key international organizations. Second, the objective of enhancing the sustainability, legitimacy and effectiveness of the global governance architecture defines the need for the flexible combination of different models of engagement of summit institutions with other international institutions. Third, according to Russia’s BRICS Presidency Concept, one of its priorities was to transition to a qualitatively new level of engagement with international organizations.The analytical framework for this study thus builds on the theory of rational choice institutionalism. The calculus approach fits the analysis of summit institutions bringing together states from a wide range of cultures, continents and economic development. Its distinctive features clearly apply to the analysis of the origin and performance of the BRICS. First, members act in a highly strategic manner to attain their priorities. Second, summitry presents an arrangement where strategic interaction among leaders plays a major role in determining political outcomes. Third, rational choice institutionalism offers the greatest analytical leverage to settings where consensus among

  9. Social defeat promotes a reactive endothelium in a brain region-dependent manner with increased expression of key adhesion molecules, selectins and chemokines associated with the recruitment of myeloid cells to the brain.

    Science.gov (United States)

    Sawicki, C M; McKim, D B; Wohleb, E S; Jarrett, B L; Reader, B F; Norden, D M; Godbout, J P; Sheridan, J F

    2015-08-27

    Repeated social defeat (RSD) in mice causes myeloid cell trafficking to the brain that contributes to the development of prolonged anxiety-like behavior. Myeloid cell recruitment following RSD occurs in regions where neuronal and microglia activation is observed. Thus, we hypothesized that crosstalk between neurons, microglia, and endothelial cells contributes to brain myeloid cell trafficking via chemokine signaling and vascular adhesion molecules. Here we show that social defeat caused an exposure- and brain region-dependent increase in several key adhesion molecules and chemokines involved in the recruitment of myeloid cells. For example, RSD induced distinct patterns of adhesion molecule expression that may explain brain region-dependent myeloid cell trafficking. VCAM-1 and ICAM-1 mRNA expression were increased in an exposure-dependent manner. Furthermore, RSD-induced VCAM-1 and ICAM-1 protein expression were localized to the vasculature of brain regions implicated in fear and anxiety responses, which spatially corresponded to previously reported patterns of myeloid cell trafficking. Next, mRNA expression of additional adhesion molecules (E- and P-selectin, PECAM-1) and chemokines (CXCL1, CXCL2, CXCL12, CCL2) were determined in the brain. Social defeat induced an exposure-dependent increase in mRNA levels of E-selectin, CXCL1, and CXCL2 that increased with additional days of social defeat. While CXCL12 was unaffected by RSD, CCL2 expression was increased by six days of social defeat. Last, comparison between enriched CD11b(+) cells (microglia/macrophages) and enriched GLAST-1(+)/CD11b(-) cells (astrocytes) revealed RSD increased mRNA expression of IL-1β, CCL2, and CXCL2 in microglia/macrophages but not in astrocytes. Collectively, these data indicate that key mediators of leukocyte recruitment were increased in the brain vasculature following RSD in an exposure- and brain region-dependent manner. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights

  10. The calmodulin inhibitor CGS 9343B inhibits voltage-dependent K{sup +} channels in rabbit coronary arterial smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hongliang; Hong, Da Hye; Kim, Han Sol; Kim, Hye Won [Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 200-701 (Korea, Republic of); Jung, Won-Kyo [Department of Biomedical Engineering, Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan 608-737 (Korea, Republic of); Na, Sung Hun [Institute of Medical Sciences, Department of Obstetrics and Gynecology, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, 200-701 (Korea, Republic of); Jung, In Duk; Park, Yeong-Min [Department of Immunology, Lab of Dendritic Cell Differentiation and Regulation, College of Medicine, Konkuk University, Chungju 380-701 (Korea, Republic of); Choi, Il-Whan, E-mail: cihima@inje.ac.kr [Department of Microbiology, Inje University College of Medicine, Busan, 614-735 (Korea, Republic of); Park, Won Sun, E-mail: parkws@kangwon.ac.kr [Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 200-701 (Korea, Republic of)

    2015-06-15

    We investigated the effects of the calmodulin inhibitor CGS 9343B on voltage-dependent K{sup +} (Kv) channels using whole-cell patch clamp technique in freshly isolated rabbit coronary arterial smooth muscle cells. CGS 9343B inhibited Kv currents in a concentration-dependent manner, with a half-maximal inhibitory concentration (IC{sub 50}) value of 0.81 μM. The decay rate of Kv channel inactivation was accelerated by CGS 9343B. The rate constants of association and dissociation for CGS 9343B were 2.77 ± 0.04 μM{sup −1} s{sup −1} and 2.55 ± 1.50 s{sup −1}, respectively. CGS 9343B did not affect the steady-state activation curve, but shifted the inactivation curve toward to a more negative potential. Train pulses (1 or 2 Hz) application progressively increased the CGS 9343B-induced Kv channel inhibition. In addition, the inactivation recovery time constant was increased in the presence of CGS 9343B, suggesting that CGS 9343B-induced inhibition of Kv channel was use-dependent. Another calmodulin inhibitor, W-13, did not affect Kv currents, and did not change the inhibitory effect of CGS 9343B on Kv current. Our results demonstrated that CGS 9343B inhibited Kv currents in a state-, time-, and use-dependent manner, independent of calmodulin inhibition. - Highlights: • We investigated the effects of CGS 9394B on Kv channels. • CGS 9394B inhibited Kv current in a state-, time-, and use-dependent manner. • Caution is required when using CGS 9394B in vascular function studies.

  11. Stat3 signaling regulates embryonic stem cell fate in a dose-dependent manner

    Directory of Open Access Journals (Sweden)

    Chih-I Tai

    2014-09-01

    Full Text Available Stat3 is essential for mouse embryonic stem cell (mESC self-renewal mediated by LIF/gp130 receptor signaling. Current understanding of Stat3-mediated ESC self-renewal mechanisms is very limited, and has heretofore been dominated by the view that Stat3 signaling functions in a binary “on/off” manner. Here, in contrast to this binary viewpoint, we demonstrate a contextual, rheostat-like mechanism for Stat3's function in mESCs. Activation and expression levels determine whether Stat3 functions in a self-renewal or a differentiation role in mESCs. We also show that Stat3 induces rapid differentiation of mESCs toward the trophectoderm (TE lineage when its activation level exceeds certain thresholds. Stat3 induces this differentiation phenotype via induction of Tfap2c and its downstream target Cdx2. Our findings provide a novel concept in the realm of Stat3, self-renewal signaling, and pluripotent stem cell biology. Ultimately, this finding may facilitate the development of conditions for the establishment of authentic non-rodent ESCs.

  12. Aplikasi Pembelajaran Table Manners Berbasis Multimedia

    OpenAIRE

    Yosanny, Agustinna; Pradipta, Albert; Viles, Dody; Pensen, Pensen

    2011-01-01

    Table manners adalah aturan-aturan pokok yang berlaku di meja makan. Aturan ini biasanya diterapkan padajamuan makan resmi. Penelitian ini bertujuan untuk merancang dan mengembangkan suatu aplikasipembelajaran tentang table manners untuk memudahkan dalam mempelajari aturan-aturan yang perlu diketahuidalam jamuan makan resmi, meliputi etika sebelum dan saat proses menyantap makanan, serta penggunaanalat-alat makan. Metode penelitian yang digunakan adalah metode Interactive Multimedia System De...

  13. Fertilizing a Patient Engagement Ecosystem to Innovate Healthcare: Toward the First Italian Consensus Conference on Patient Engagement.

    Science.gov (United States)

    Graffigna, Guendalina; Barello, Serena; Riva, Giuseppe; Savarese, Mariarosaria; Menichetti, Julia; Castelnuovo, Gianluca; Corbo, Massimo; Tzannis, Alessandra; Aglione, Antonio; Bettega, Donato; Bertoni, Anna; Bigi, Sarah; Bruttomesso, Daniela; Carzaniga, Claudia; Del Campo, Laura; Donato, Silvia; Gilardi, Silvia; Guglielmetti, Chiara; Gulizia, Michele; Lastretti, Mara; Mastrilli, Valeria; Mazzone, Antonino; Muttillo, Giovanni; Ostuzzi, Silvia; Perseghin, Gianluca; Piana, Natalia; Pitacco, Giuliana; Polvani, Gianluca; Pozzi, Massimo; Provenzi, Livio; Quaglini, Giulia; Rossi, Mariagrazia; Varese, Paola; Visalli, Natalia; Vegni, Elena; Ricciardi, Walter; Bosio, A Claudio

    2017-01-01

    Currently we observe a gap between theory and practices of patient engagement. If both scholars and health practitioners do agree on the urgency to realize patient engagement, no shared guidelines exist so far to orient clinical practice. Despite a supportive policy context, progress to achieve greater patient engagement is patchy and slow and often concentrated at the level of policy regulation without dialoguing with practitioners from the clinical field as well as patients and families. Though individual clinicians, care teams and health organizations may be interested and deeply committed to engage patients and family members in the medical course, they may lack clarity about how to achieve this goal. This contributes to a wide "system" inertia-really difficult to be overcome-and put at risk any form of innovation in this filed. As a result, patient engagement risk today to be a buzz words, rather than a real guidance for practice. To make the field clearer, we promoted an Italian Consensus Conference on Patient Engagement (ICCPE) in order to set the ground for drafting recommendations for the provision of effective patient engagement interventions. The ICCPE will conclude in June 2017. This document reports on the preliminary phases of this process. In the paper, we advise the importance of "fertilizing a patient engagement ecosystem": an oversimplifying approach to patient engagement promotion appears the result of a common illusion. Patient "disengagement" is a symptom that needs a more holistic and complex approach to solve its underlined causes. Preliminary principles to promote a patient engagement ecosystem are provided in the paper.

  14. Pragmatics in Action: Indirect Requests Engage Theory of Mind Areas and the Cortical Motor Network

    NARCIS (Netherlands)

    Ackeren, M.J. van; Casasanto, D.; Bekkering, H.; Hagoort, P.; Ruschemeyer, S.A.

    2012-01-01

    Research from the past decade has shown that understanding the meaning of words and utterances (i.e., abstracted symbols) engages the same systems we used to perceive and interact with the physical world in a content-specific manner. For example, understanding the word "grasp" elicits activation in

  15. Analysis of engagement behavior in children during dyadic interactions using prosodic cues.

    Science.gov (United States)

    Gupta, Rahul; Bone, Daniel; Lee, Sungbok; Narayanan, Shrikanth

    2016-05-01

    Child engagement is defined as the interaction of a child with his/her environment in a contextually appropriate manner. Engagement behavior in children is linked to socio-emotional and cognitive state assessment with enhanced engagement identified with improved skills. A vast majority of studies however rely solely, and often implicitly, on subjective perceptual measures of engagement. Access to automatic quantification could assist researchers/clinicians to objectively interpret engagement with respect to a target behavior or condition, and furthermore inform mechanisms for improving engagement in various settings. In this paper, we present an engagement prediction system based exclusively on vocal cues observed during structured interaction between a child and a psychologist involving several tasks. Specifically, we derive prosodic cues that capture engagement levels across the various tasks. Our experiments suggest that a child's engagement is reflected not only in the vocalizations, but also in the speech of the interacting psychologist. Moreover, we show that prosodic cues are informative of the engagement phenomena not only as characterized over the entire task (i.e., global cues), but also in short term patterns (i.e., local cues). We perform a classification experiment assigning the engagement of a child into three discrete levels achieving an unweighted average recall of 55.8% (chance is 33.3%). While the systems using global cues and local level cues are each statistically significant in predicting engagement, we obtain the best results after fusing these two components. We perform further analysis of the cues at local and global levels to achieve insights linking specific prosodic patterns to the engagement phenomenon. We observe that while the performance of our model varies with task setting and interacting psychologist, there exist universal prosodic patterns reflective of engagement.

  16. Influence of the size of facets on point focus solar concentrators

    Energy Technology Data Exchange (ETDEWEB)

    Riveros-Rosas, David [Instituto de Geofisica, Universidad Nacional Autonoma de Mexico, Ciudad Universitaria, Col. Copilco, Coyoacan, CP 04510 DF (Mexico); Sanchez-Gonzalez, Marcelino [Centro Nacional de Energias Renovables, c/Somera 7-9, CP 28026 Madrid (Spain); Arancibia-Bulnes, Camilo A.; Estrada, Claudio A. [Centro de Investigacion en Energia, Universidad Nacional Autonoma de Mexico, Priv. Xochicalco s/n, Morelos (Mexico)

    2011-03-15

    It is a common practice in the development of point focus solar concentrators to use multiple identical reflecting facets, as a practical and economic alternative for the design and construction of large systems. This kind of systems behaves in a different manner than continuous paraboloidal concentrators. A theoretical study is carried out to understand the effect of the size of facets and of their optical errors in multiple facet point focus solar concentrating systems. For this purpose, a ray tracing program was developed based on the convolution technique, in which the brightness distribution of the sun and the optical errors of the reflecting surfaces are considered. The study shows that both the peak of concentration and the optimal focal distance of the system strongly depend on the size of the facets, and on their optical errors. These results are useful to help concentrator developers to have a better understanding of the relationship between manufacturing design restrictions and final optical behavior. (author)

  17. Dependence of aggregation behavior on concentration in triblock copolymer solutions: The effect of chain architecture

    International Nuclear Information System (INIS)

    Han, Xiang-Gang; Zhang, Xue-Feng

    2015-01-01

    Using the self-consistent field lattice technique, the effects of concentration and hydrophobic middle block length (where the chain length remains constant) on aggregation behavior are studied in amphiphilic symmetric triblock copolymer solutions. The heat capacity peak for the unimer-micelle transition and the distribution peaks for the different degrees of aggregation for micelles and small aggregates (submicelles) are calculated. Analysis of the conducted computer simulations shows that the transition broadness dependence on concentration is determined by the hydrophobic middle block length, and this dependence is distinctly different when the length of the hydrophobic middle block changes. Different size for small aggregates simultaneously appear in the transition region. As temperature decreases, the number of different size small aggregates for the large hydrophobic middle block length first ascends and then descends in aggregation degree order. These results indicate that any transition broadness change with concentration is related to the mechanism of fragmentation and fusion. These results are helpful for interpreting the aggregation process of amphiphilic copolymers at equilibrium

  18. Size-dependent concentration of N0 paramagnetic centres in HPHT nanodiamonds

    Directory of Open Access Journals (Sweden)

    B.V. Yavkin, G.V. Mamin, M.R. Gafurov, S.B. Orlinskii

    2015-12-01

    Full Text Available Size-calibrated commercial nanodiamonds synthesized by high-pressure high-temperature (HPHT technique were studied by high-frequency W- and conventional X-band electron paramagnetic resonance (EPR spectroscopy. The numbers of spins in the studied samples were estimated. The core-shell model of the HPHT nanodiamonds was proposed to explain the observed dependence of the concentration of the N0 paramagnetic centers. Two other observed paramagnetic centers are attributed to the two types of structures in the nanodiamond shell.

  19. Barriers to Engagement in a Workplace Weight Management Program: A Qualitative Study.

    Science.gov (United States)

    Clancy, Shayna M; Stroo, Marissa; Schoenfisch, Ashley; Dabrera, Thushani; Østbye, Truls

    2018-03-01

    To investigate (1) why some participants in a workplace weight management program were more engaged in the program, (2) specific barriers and facilitators for engagement and weight loss, and (3) suggest how workplaces may better engage employees in these programs to improve their effectiveness. Qualitative study (8 focus groups). A large academic university and medical system. Twenty-six (5%) of the 550 employees who participated in a weight management program as part of the Steps to Health study. A trained moderator guided the audio-recorded focus groups. Transcripts were analyzed using the directed content analysis approach. Participants faced numerous barriers to engagement in workplace weight management programs, both within and outside the workplace. Participants viewed the coaches positively and reported that the coaches had a strong influence on their engagement in the program. Participants suggested increased frequency and variety of contact by coaches, on-site group exercise classes, and tailored educational materials. Workplace weight management programs may be improved by being more flexible around participants' schedules and changing needs, by increasing access to affordable, convenient exercise facilities, and by implementing institutional changes that encourage healthy eating and physical activity during the workday. Employers should measure program engagement and solicit participant feedback to ensure that the programs are appropriate and delivered in an optimal manner.

  20. β-Arrestin-dependent deactivation of mouse melanopsin.

    Directory of Open Access Journals (Sweden)

    Evan G Cameron

    Full Text Available In mammals, the expression of the unusual visual pigment, melanopsin, is restricted to a small subset of intrinsically photosensitive retinal ganglion cells (ipRGCs, whose signaling regulate numerous non-visual functions including sleep, circadian photoentrainment and pupillary constriction. IpRGCs exhibit attenuated electrical responses following sequential and prolonged light exposures indicative of an adaptational response. The molecular mechanisms underlying deactivation and adaptation in ipRGCs however, have yet to be fully elucidated. The role of melanopsin phosphorylation and β-arrestin binding in this adaptive process is suggested by the phosphorylation-dependent reduction of melanopsin signaling in vitro and the ubiquitous expression of β-arrestin in the retina. These observations, along with the conspicuous absence of visual arrestin in ipRGCs, suggest that a β-arrestin terminates melanopsin signaling. Here, we describe a light- and phosphorylation- dependent reduction in melanopsin signaling mediated by both β-arrestin 1 and β-arrestin 2. Using an in vitro calcium imaging assay, we demonstrate that increasing the cellular concentration of β-arrestin 1 and β-arrestin 2 significantly increases the rate of deactivation of light-activated melanopsin in HEK293 cells. Furthermore, we show that this response is dependent on melanopsin carboxyl-tail phosphorylation. Crosslinking and co-immunoprecipitation experiments confirm β-arrestin 1 and β-arrestin 2 bind to melanopsin in a light- and phosphorylation- dependent manner. These data are further supported by proximity ligation assays (PLA, which demonstrate a melanopsin/β-arrestin interaction in HEK293 cells and ipRGCs. Together, these results suggest that melanopsin signaling is terminated in a light- and phosphorylation-dependent manner through the binding of a β-arrestin within the retina.

  1. Using stakeholder engagement to develop a patient-centered pediatric asthma intervention.

    Science.gov (United States)

    Shelef, Deborah Q; Rand, Cynthia; Streisand, Randi; Horn, Ivor B; Yadav, Kabir; Stewart, Lisa; Fousheé, Naja; Waters, Damian; Teach, Stephen J

    2016-12-01

    Stakeholder engagement has the potential to develop research interventions that are responsive to patient and provider preferences. This approach contrasts with traditional models of clinical research in which researchers determine the study's design. This article describes the effect of stakeholder engagement on the design of a randomized trial of an intervention designed to improve child asthma outcomes by reducing parental stress. The study team developed and implemented a stakeholder engagement process that provided iterative feedback regarding the study design, patient-centered outcomes, and intervention. Stakeholder engagement incorporated the perspectives of parents of children with asthma; local providers of community-based medical, legal, and social services; and national experts in asthma research methodology and implementation. Through a year-long process of multidimensional stakeholder engagement, the research team successfully refined and implemented a patient-centered study protocol. Key stakeholder contributions included selection of patient-centered outcome measures, refinement of intervention content and format, and language framing the study in a culturally appropriate manner. Stakeholder engagement was a useful framework for developing an intervention that was acceptable and relevant to our target population. This approach might have unique benefits in underserved populations, leading to sustainable improvement in health outcomes and reduced disparities. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  2. Non-natural manners of death among users of illicit drugs: Substance findings.

    Science.gov (United States)

    Delaveris, Gerd Jorunn M; Teige, Brita; Rogde, Sidsel

    2014-05-01

    The aim of the study was to explore differences and similarities between the various non-natural manners of death (accident, suicide, homicide) regarding toxicological findings in illicit drug users. Medicolegal autopsy reports from the Institute of Forensic Medicine University of Oslo concerning deaths from 2000 to 2009 were investigated. Those aged 20-59 whose manner of death was non-natural and who tested positive for any narcotic drug (morphine/heroin, amphetamines, ecstasy, cannabis, LSD, PCP, and high levels of GHB in addition to methadone and buprenorphine) were selected. All substance findings were registered and categorized (narcotics, ethanol, and medicinal products). Of the 1603 autopsies that met the selection criteria, 1204 were accidental intoxications, 122 accidents other than intoxication, 114 suicides by intoxication, 119 non-intoxication suicides, and 44 victims of homicide. Poly drug use was found in all manners of death. The drug profile as well as the mean number of substances (illicit drugs and medicinal products) varied from 2.9 to 4.6 substances per case, depending on the manner of death. Intoxication suicides had the highest number of substances and a total drug profile similar to accidental intoxications. Non-intoxication suicides had a total drug profile similar to homicide and accidents other than intoxication. The number of substances found per case increased during the decade, mainly due to increased findings of methadone, cannabis, amphetamines, and benzodiazepines. Methadone findings increased much more than buprenorphine. Methadone was found 20 times more often than buprenorphine in accidental intoxication cases. In summary, poly drug findings are common in adults who suffer a non-natural death while using illicit drugs. The different manners of death have some specific characteristics and significant differences regarding drug profile. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Facilitating neurorehabilitation through principles of engagement.

    Science.gov (United States)

    Danzl, Megan M; Etter, Nicole M; Andreatta, Richard D; Kitzman, Patrick H

    2012-01-01

    A primary goal of neurorehabilitation is to guide recovery of functional skills after injury through evidence-based interventions that operate to manipulate the sensorimotor environment of the client. While choice of intervention is an important decision for clinicians, we contend it is only one part of producing optimal activity-dependent neuroplastic changes. A key variable in the rehabilitation equation is engagement. Applying principles of engagement may yield greater neuroplastic changes and functional outcomes for clients. We review the principles of neuroplasticity and engagement and their potential linkage through concepts of attention and motivation and strategies such as mental practice and enriched environments. Clinical applications and challenges for enhancing engagement during rehabilitation are presented. Engagement strategies, such as building trust and rapport, motivational interviewing, enhancing the client education process, and interventions that empower clients, are reviewed. Well-controlled research is needed to test our theoretical framework and suggested outcomes. Clinicians may enhance engagement by investing time and energy in the growth and development of the therapeutic relationship with clients, as this is paramount to maintaining clients' investment in continuing therapy and also may act as a driver of neuroplastic changes.

  4. A NOVEL INTERPRETATION OF CONCENTRATION DEPENDENCE OF VISCOSITY OF DILUTE POLYMER SOLUTION

    Institute of Scientific and Technical Information of China (English)

    Yan Pan; Rong-shi Cheng

    2000-01-01

    The concentration dependence of the reduced viscosity of dilute polymer solution is interpreted in the light of a new concept of the self-association of polymer chains in dilute solution. The apparent self-association constant is defined as the molar association constant divided by the molar mass of individual polymer chain and is numerically interconvertible with the Huggins coefficient. The molar association constant is directly proportional to the effective hydrodynamic volume of the polymer chain in solution and is irrespective of the chain architecture. The effective hydrodynamic volume accounts for the non-spherical conformation of a short polymer chain in solution and is a product of a shape factor and hydrodynamic volume. The observed enhancement of Huggins coefficient for short chain and branched polymer is satisfactorily interpreted by the concept of self-association. The concept of self-association allows us to predict the existence of a boundary concentration Cs (dynamic contact concentration) which divides the dilute polymer solution into two regions.

  5. FBAR syndapin 1 recognizes and stabilizes highly curved tubular membranes in a concentration dependent manner

    DEFF Research Database (Denmark)

    Ramesh, Pradeep; Baroji, Younes F.; Seyyed Reihani, Seyyed Nader

    2013-01-01

    Syndapin 1 FBAR, a member of the Bin-amphiphysin-Rvs (BAR) domain protein family, is known to induce membrane curvature and is an essential component in biological processes like endocytosis and formation and growth of neurites. We quantify the curvature sensing of FBAR on reconstituted porcine b...

  6. Solute concentration dependence of the decay curves of the liquid scintillation

    International Nuclear Information System (INIS)

    Onishi, Masayoshi; Niki, Eiji.

    1976-01-01

    The decay curves of the liquid scintillation of 2,5-diphenyloxazole (PPO) in toluene by the irradiation of β ray from 14 C were measured. Solute concentration dependences of the decay times of the fast and slow components were studied. The decay time tau sub(f) of the fast component of the air saturated scintillator was the smallest at 1.8x10 -2 --4.5x10 -2 mol/l, and about (3.4--3.5)ns. When the concentration became less than 1.8x10 -2 mol/l, the peak of the decay curve became roundish and the pulse width became large. The increase of the necessary time for the energy transfer due to the difficulty of the nonradiative transfer from excited solvent molecules to the solute was the reason. When the concentration became less than about 2.26x10 -3 mol/l, tau sub(f) became larger and the energy transfer became radiative. The pulse width and tau sub(f) were very small because of oxygen quenching compared with oxygen free. At higher concentrations such as 1.6x10 -1 and 2.3x10 -1 mol/l, the effect of the PPO excimer was observed on the fast component, and tau sub(f) became larger apparently. This denied the presumption of the close relation between PPO molecular interaction and the slow component together with the fact that the decay time tau sub(s) of the slow component was independent of PPO concentration. (auth.)

  7. Enriched environment influences hormonal status and hippocampal brain derived neurotrophic factor in a sex dependent manner.

    Science.gov (United States)

    Bakos, J; Hlavacova, N; Rajman, M; Ondicova, K; Koros, C; Kitraki, E; Steinbusch, H W M; Jezova, D

    2009-12-01

    The present study is aimed at testing the hypothesis that an enriched environment (EE) induces sex-dependent changes in stress hormone release and in markers of increased brain plasticity. The focus was on hypothalamic-pituitary-adrenocortical (HPA) axis activity, plasma levels of stress hormones, gene expression of glutamate receptor subunits and concentrations of brain-derived neurotrophic factor (BDNF) in selected brain regions. Rats exposed to EE were housed in groups of 12 in large cages with various objects, which were frequently changed, for 6 weeks. Control animals were housed four per cage under standard conditions. In females the EE-induced rise in hippocampal BDNF, a neurotrophic factor associated with increased neural plasticity, was more pronounced than in males. Similar sex-specific changes were observed in BDNF concentrations in the hypothalamus. EE also significantly attenuated oxytocin and aldosterone levels only in female but not male rats. Plasma testosterone positively correlated with hippocampal BDNF in female but not male rats housed in EE. In male rats housing in EE led to enhanced levels of testosterone and adrenocorticotropic hormone (ACTH), this was not seen in females. Hippocampal glucocorticoid but not mineralocorticoid receptor levels decreased in rats housed in EE irrespective of sex. Housing conditions failed to modify mRNA levels of glutamate receptor type 1 (Glur1) and metabotropic glutamate receptor subtype 5 (mGlur5) subunits of glutamate receptors in the forebrain. Moreover, a negative association between corticosterone and BDNF was observed in both sexes. The results demonstrate that the association between hormones and changes in brain plasticity is sex related. In particular, testosterone seems to be involved in the regulatory processes related to neuroplasticity in females.

  8. Fertilizing a Patient Engagement Ecosystem to Innovate Healthcare: Toward the First Italian Consensus Conference on Patient Engagement

    Directory of Open Access Journals (Sweden)

    Guendalina Graffigna

    2017-06-01

    Full Text Available Currently we observe a gap between theory and practices of patient engagement. If both scholars and health practitioners do agree on the urgency to realize patient engagement, no shared guidelines exist so far to orient clinical practice. Despite a supportive policy context, progress to achieve greater patient engagement is patchy and slow and often concentrated at the level of policy regulation without dialoguing with practitioners from the clinical field as well as patients and families. Though individual clinicians, care teams and health organizations may be interested and deeply committed to engage patients and family members in the medical course, they may lack clarity about how to achieve this goal. This contributes to a wide “system” inertia—really difficult to be overcome—and put at risk any form of innovation in this filed. As a result, patient engagement risk today to be a buzz words, rather than a real guidance for practice. To make the field clearer, we promoted an Italian Consensus Conference on Patient Engagement (ICCPE in order to set the ground for drafting recommendations for the provision of effective patient engagement interventions. The ICCPE will conclude in June 2017. This document reports on the preliminary phases of this process. In the paper, we advise the importance of “fertilizing a patient engagement ecosystem”: an oversimplifying approach to patient engagement promotion appears the result of a common illusion. Patient “disengagement” is a symptom that needs a more holistic and complex approach to solve its underlined causes. Preliminary principles to promote a patient engagement ecosystem are provided in the paper.

  9. Three-Dimensional Finite Element Analysis on Stress Distribution of Internal Implant-Abutment Engagement Features.

    Science.gov (United States)

    Cho, Sung-Yong; Huh, Yun-Hyuk; Park, Chan-Jin; Cho, Lee-Ra

    To investigate the stress distribution in an implant-abutment complex with a preloaded abutment screw by comparing implant-abutment engagement features using three-dimensional finite element analysis (FEA). For FEA modeling, two implants-one with a single (S) engagement system and the other with a double (D) engagement system-were placed in the human mandibular molar region. Two types of abutments (hexagonal, conical) were connected to the implants. Different implant models (a single implant, two parallel implants, and mesial and tilted distal implants with 1-mm bone loss) were assumed. A static axial force and a 45-degree oblique force of 200 N were applied as the sum of vectors to the top of the prosthetic occlusal surface with a preload of 30 Ncm in the abutment screw. The von Mises stresses at the implant-abutment and abutment-screw interfaces were measured. In the single implant model, the S-conical abutment type exhibited broader stress distribution than the S-hexagonal abutment. In the double engagement system, the stress concentration was high in the lower contact area of the implant-abutment engagement. In the tilted implant model, the stress concentration point was different from that in the parallel implant model because of the difference in the bone level. The double engagement system demonstrated a high stress concentration at the lower contact area of the implant-abutment interface. To decrease the stress concentration, the type of engagement features of the implant-abutment connection should be carefully considered.

  10. Concentration-dependent toxicity of iron oxide nanoparticles mediated by increased oxidative stress

    Directory of Open Access Journals (Sweden)

    Saba Naqvi

    2010-11-01

    Full Text Available Saba Naqvi1, Mohammad Samim2, MZ Abdin3, Farhan Jalees Ahmed4, AN Maitra5, CK Prashant6, Amit K Dinda61Faculty of Engineering and Interdisciplinary Sciences, 2Department of Chemistry, 3Department of Biotechnology, Faculty of Science, 4Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard University, 5Department of Chemistry, University of Delhi, 6Department of Pathology, All India Institute of Medical Sciences, New Delhi, IndiaAbstract: Iron oxide nanoparticles with unique magnetic properties have a high potential for use in several biomedical, bioengineering and in vivo applications, including tissue repair, magnetic resonance imaging, immunoassay, drug delivery, detoxification of biologic fluids, cell sorting, and hyperthermia. Although various surface modifications are being done for making these nonbiodegradable nanoparticles more biocompatible, their toxic potential is still a major concern. The current in vitro study of the interaction of superparamagnetic iron oxide nanoparticles of mean diameter 30 nm coated with Tween 80 and murine macrophage (J774 cells was undertaken to evaluate the dose- and time-dependent toxic potential, as well as investigate the role of oxidative stress in the toxicity. A 15–30 nm size range of spherical nanoparticles were characterized by transmission electron microscopy and zeta sizer. MTT assay showed >95% viability of cells in lower concentrations (25–200 µg/mL and up to three hours of exposure, whereas at higher concentrations (300–500 µg/mL and prolonged (six hours exposure viability reduced to 55%–65%. Necrosis-apoptosis assay by propidium iodide and Hoechst-33342 staining revealed loss of the majority of the cells by apoptosis. H2DCFDDA assay to quantify generation of intracellular reactive oxygen species (ROS indicated that exposure to a higher concentration of nanoparticles resulted in enhanced ROS generation, leading to cell injury and death. The cell membrane injury

  11. Influence of Missile Fusillade Engagement Mode on Operation Efficiency

    Institute of Scientific and Technical Information of China (English)

    BU Xian-jin; REN Yi-guang; SHA Ji-chang

    2008-01-01

    Shoot efficiency is one of the most important evaluation indexes of the operation efficiency of weapon system. In this paper, based on definitions of the probability and the expected number of missed attacking missiles, the expected numbers of anti-missiles and attacking missiles hit by single anti-missile, fusillade mechanism of multi-missile is analyzed systematically. The weapon operation efficiency in various engagement patterns is also studied. The results show that double missiles fusillade is the most feasible manner for increasing the weapon operation efficiency.

  12. Concentration-dependent gene expression responses to flusilazole in embryonic stem cell differentiation cultures

    International Nuclear Information System (INIS)

    Dartel, Dorien A.M. van; Pennings, Jeroen L.A.; Fonteyne, Liset J.J. de la; Brauers, Karen J.J.; Claessen, Sandra; Delft, Joost H. van; Kleinjans, Jos C.S.; Piersma, Aldert H.

    2011-01-01

    The murine embryonic stem cell test (EST) is designed to evaluate developmental toxicity based on compound-induced inhibition of embryonic stem cell (ESC) differentiation into cardiomyocytes. The addition of transcriptomic evaluation within the EST may result in enhanced predictability and improved characterization of the applicability domain, therefore improving usage of the EST for regulatory testing strategies. Transcriptomic analyses assessing factors critical for risk assessment (i.e. dose) are needed to determine the value of transcriptomic evaluation in the EST. Here, using the developmentally toxic compound, flusilazole, we investigated the effect of compound concentration on gene expression regulation and toxicity prediction in ESC differentiation cultures. Cultures were exposed for 24 h to multiple concentrations of flusilazole (0.54-54 μM) and RNA was isolated. In addition, we sampled control cultures 0, 24, and 48 h to evaluate the transcriptomic status of the cultures across differentiation. Transcriptomic profiling identified a higher sensitivity of development-related processes as compared to cell division-related processes in flusilazole-exposed differentiation cultures. Furthermore, the sterol synthesis-related mode of action of flusilazole toxicity was detected. Principal component analysis using gene sets related to normal ESC differentiation was used to describe the dynamics of ESC differentiation, defined as the 'differentiation track'. The concentration-dependent effects on development were reflected in the significance of deviation of flusilazole-exposed cultures from this transcriptomic-based differentiation track. Thus, the detection of developmental toxicity in EST using transcriptomics was shown to be compound concentration-dependent. This study provides further insight into the possible application of transcriptomics in the EST as an improved alternative model system for developmental toxicity testing.

  13. Serial changes in plasma K concentration during storage of irradiation blood products

    International Nuclear Information System (INIS)

    Togashi, Kazue; Yamada, Keiko; Otake, Sachiko; Saito, Yukiko; Sugimura, Kazuhito; Takahashi, Hoyu

    1996-01-01

    Irradiation of blood products is highly effective in the prevention of transfusion-associated graft-versus-host disease (GVHD). In order to assess the safe storage period of irradiated blood products, serial changes in plasma K, red cell 2,3-diphosphoglycerate (2,3-DPG) and lactic acid concentrations of whole blood and M·A·P-added red cell concentrate (RC-M·A·P) during storage at 5degC were measured after irradiation with 137 Cs by IBL 437C (CIS bio international). Plasma K concentration did not change immediately after irradiation, but increased more rapidly and in a radiation dose-dependent manner in the irradiated products than nonirradiated products. The changes in red cell 2,3-DPG and lactic acid concentrations were not affected by irradiation but were rather dependent on the storage period after blood collection. Plasma K concentrations of whole blood and RC-M·A·P irradiated with 25 Gy increased at 5 and 3 days, respectively, to the K levels observed after the storage of nonirradiated products for 21 days. It is therefore recommended that whole blood be used within 5 days and RC-M·A·P within 3 days when stored after irradiation with 25 Gy. (author)

  14. 29 CFR 1905.21 - Manner of service.

    Science.gov (United States)

    2010-07-01

    ...-STEIGER OCCUPATIONAL SAFETY AND HEALTH ACT OF 1970 Hearings § 1905.21 Manner of service. Service of any... 29 Labor 5 2010-07-01 2010-07-01 false Manner of service. 1905.21 Section 1905.21 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR...

  15. Upconversion NaYF4 Nanoparticles for Size Dependent Cell Imaging and Concentration Dependent Detection of Rhodamine B

    Directory of Open Access Journals (Sweden)

    Shigang Hu

    2015-01-01

    Full Text Available Upconversion nanoparticles (UCNPs based on NaYF4 nanocrystals with strong upconversion luminescence are synthesized by the solvothermal method. The emission color of these NaYF4 upconversion nanoparticles can be easily modulated by the doping. These NaYF4 upconversion nanocrystals can be employed as fluorescence donors to pump fluorescent organic molecules. For example, the efficient luminescence resonant energy transfer (LRET can be achieved by controlling the distance between NaYF4:Yb3+/Er3+ UCNPs and Rhodamine B (RB. NaYF4:Yb3+/Er3+ UCNPs can emit green light at the wavelength of ~540 nm while RB can efficiently absorb the green light of ~540 nm to emit red light of 610 nm. The LRET efficiency is highly dependent on the concentration of NaYF4 upconversion fluorescent donors. For the fixed concentration of 3.2 µg/mL RB, the optimal concentration of NaYF4:Yb3+/Er3+ UCNPs is equal to 4 mg/mL which generates the highest LRET signal ratio. In addition, it is addressed that the upconversion nanoparticles with diameter of 200 nm are suitable for imaging the cells larger than 10 µm with clear differentiation between cell walls and cytoplasm.

  16. Ghrelin decreases firing activity of gonadotropin-releasing hormone (GnRH neurons in an estrous cycle and endocannabinoid signaling dependent manner.

    Directory of Open Access Journals (Sweden)

    Imre Farkas

    Full Text Available The orexigenic peptide, ghrelin is known to influence function of GnRH neurons, however, the direct effects of the hormone upon these neurons have not been explored, yet. The present study was undertaken to reveal expression of growth hormone secretagogue receptor (GHS-R in GnRH neurons and elucidate the mechanisms of ghrelin actions upon them. Ca(2+-imaging revealed a ghrelin-triggered increase of the Ca(2+-content in GT1-7 neurons kept in a steroid-free medium, which was abolished by GHS-R-antagonist JMV2959 (10 µM suggesting direct action of ghrelin. Estradiol (1nM eliminated the ghrelin-evoked rise of Ca(2+-content, indicating the estradiol dependency of the process. Expression of GHS-R mRNA was then confirmed in GnRH-GFP neurons of transgenic mice by single cell RT-PCR. Firing rate and burst frequency of GnRH-GFP neurons were lower in metestrous than proestrous mice. Ghrelin (40 nM-4 μM administration resulted in a decreased firing rate and burst frequency of GnRH neurons in metestrous, but not in proestrous mice. Ghrelin also decreased the firing rate of GnRH neurons in males. The ghrelin-evoked alterations of the firing parameters were prevented by JMV2959, supporting the receptor-specific actions of ghrelin on GnRH neurons. In metestrous mice, ghrelin decreased the frequency of GABAergic mPSCs in GnRH neurons. Effects of ghrelin were abolished by the cannabinoid receptor type-1 (CB1 antagonist AM251 (1µM and the intracellularly applied DAG-lipase inhibitor THL (10 µM, indicating the involvement of retrograde endocannabinoid signaling. These findings demonstrate that ghrelin exerts direct regulatory effects on GnRH neurons via GHS-R, and modulates the firing of GnRH neurons in an ovarian-cycle and endocannabinoid dependent manner.

  17. De novo generation of helper virus-satellite chimera RNAs results in disease attenuation and satellite sequence acquisition in a host-dependent manner.

    Science.gov (United States)

    Pyle, J D; Scholthof, Karen-Beth G

    2018-01-15

    Panicum mosaic virus (PMV) is a helper RNA virus for satellite RNAs (satRNAs) and a satellite virus (SPMV). Here, we describe modifications that occur at the 3'-end of a satRNA of PMV, satS. Co-infections of PMV+satS result in attenuation of the disease symptoms induced by PMV alone in Brachypodium distachyon and proso millet. The 375 nt satS acquires ~100-200 nts from the 3'-end of PMV during infection and is associated with decreased abundance of the PMV RNA and capsid protein in millet. PMV-satS chimera RNAs were isolated from native infections of St. Augustinegrass and switchgrass. Phylogenetic analyses revealed that the chimeric RNAs clustered according to the host species from which they were isolated. Additionally, the chimera satRNAs acquired non-viral "linker" sequences in a host-specific manner. These results highlight the dynamic regulation of viral pathogenicity by satellites, and the selective host-dependent, sequence-based pressures for driving satRNA generation and genome compositions. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Practical theology: A critically engaged practical reason approach of ...

    African Journals Online (AJOL)

    This article seeks to present a critically engaged practical reasoning approach in which theory and practice have an in-ter-dependent relationship. Practical reason is an activity in which engagement happens at every stage. For this to happen, theory and practice interact as equal variables that have a bearing on each other ...

  19. Exploring a Middle Ground Engagement with Students in a Social Learning Environment.

    Science.gov (United States)

    Smith, Anne M. J.; Campbell, Sonya

    2012-01-01

    The twenty first century student demands more from universities in terms of engagement that is flexible, accessible and immediate. This means universities revisiting their engagement agenda at a time when financial constraints can least afford expensive technologies and resource dependent engagement solutions. Solutions are likely to be varied…

  20. Plasmin-driven fibrinolysis facilitates skin tumor growth in a gender-dependent manner

    DEFF Research Database (Denmark)

    Hald, Andreas; Eickhardt, Hanne; Maerkedahl, Rasmus Baadsgaard

    2012-01-01

    deficiency was due to thrombosis and lost patency of the tumor vasculature, resulting in tumor necrosis. The connection between plasmin-dependent fibrinolysis, vascular patency, and tumor growth was further substantiated as the effect of plasminogen deficiency on tumor growth could be reverted...

  1. Why do patients engage in medical tourism?

    Science.gov (United States)

    Runnels, Vivien; Carrera, P M

    2012-12-01

    Medical tourism is commonly perceived and popularly depicted as an economic issue, both at the system and individual levels. The decision to engage in medical tourism, however, is more complex, driven by patients' unmet need, the nature of services sought and the manner by which treatment is accessed. In order to beneficially employ the opportunities medical tourism offers, and address and contain possible threats and harms, an informed decision is crucial. This paper aims to enhance the current knowledge on medical tourism by isolating the focal content of the decisions that patients make. Based on the existing literature, it proposes a sequential decision-making process in opting for or against medical care abroad, and engaging in medical tourism, including considerations of the required treatments, location of treatment, and quality and safety issues attendant to seeking care. Accordingly, it comments on the imperative of access to health information and the current regulatory environment which impact on this increasingly popular and complex form of accessing and providing medical care. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. Modelling reaustenitisation in Fe-C steels with concentration-dependent diffusivity of carbon

    Directory of Open Access Journals (Sweden)

    Mancini, R.

    2002-12-01

    Full Text Available A finite difference method used to model reaustenitisation from a ferrite/cementite mixture in Fe-C steels is presented in this paper. Concentration-dependent carbon diffusivity in austenite is taken into account in order to generalize our earlier numerical model. We select some parameters, such as cementite dissolution time, and compare their values as calculated by different approximations available in the literature (in particular at steady state for planar and spherical geometries. When the dependence of diffusivity on concentration or temperature is increased, the steady state approximation fails to predict correctly the above mentioned parameters and the use of numerical techniques becomes indispensable.

    En este trabajo se presenta un método numérico de diferencias finitas para modelar la reaustenización en aceros Fe-C a partir de una distribución inicial de ferrita y cementita. Se tiene en cuenta la dependencia de la difusividad en la austenita con la concentración de carbono, a fin de generalizar el propio modelo numérico previo. Se han seleccionado algunos parámetros, como el tiempo de disolución de la cementita, para comparar los valores obtenidos en este caso con los calculados con diferentes aproximaciones (en particular con la de estado estacionario para los casos de geometrías plana y esférica. Los resultados obtenidos muestran que, cuando la difusividad depende fuertemente de la concentración, la aproximación de estado estacionario no predice correctamente los parámetros calculados y se hace imprescindible la aplicación de métodos numéricos.

  3. Astrocytes Can Adopt Endothelial Cell Fates in a p53-Dependent Manner.

    Science.gov (United States)

    Brumm, Andrew J; Nunez, Stefanie; Doroudchi, Mehdi M; Kawaguchi, Riki; Duan, Jinhzu; Pellegrini, Matteo; Lam, Larry; Carmichael, S Thomas; Deb, Arjun; Hinman, Jason D

    2017-08-01

    Astrocytes respond to a variety of CNS injuries by cellular enlargement, process outgrowth, and upregulation of extracellular matrix proteins that function to prevent expansion of the injured region. This astrocytic response, though critical to the acute injury response, results in the formation of a glial scar that inhibits neural repair. Scar-forming cells (fibroblasts) in the heart can undergo mesenchymal-endothelial transition into endothelial cell fates following cardiac injury in a process dependent on p53 that can be modulated to augment cardiac repair. Here, we sought to determine whether astrocytes, as the primary scar-forming cell of the CNS, are able to undergo a similar cellular phenotypic transition and adopt endothelial cell fates. Serum deprivation of differentiated astrocytes resulted in a change in cellular morphology and upregulation of endothelial cell marker genes. In a tube formation assay, serum-deprived astrocytes showed a substantial increase in vessel-like morphology that was comparable to human umbilical vein endothelial cells and dependent on p53. RNA sequencing of serum-deprived astrocytes demonstrated an expression profile that mimicked an endothelial rather than astrocyte transcriptome and identified p53 and angiogenic pathways as specifically upregulated. Inhibition of p53 with genetic or pharmacologic strategies inhibited astrocyte-endothelial transition. Astrocyte-endothelial cell transition could also be modulated by miR-194, a microRNA downstream of p53 that affects expression of genes regulating angiogenesis. Together, these studies demonstrate that differentiated astrocytes retain a stimulus-dependent mechanism for cellular transition into an endothelial phenotype that may modulate formation of the glial scar and promote injury-induced angiogenesis.

  4. Meaning creation and employee engagement in home health caregivers.

    Science.gov (United States)

    Nielsen, Mette Strange; Jørgensen, Frances

    2016-03-01

    The purpose of this study is to contribute to an understanding on how home health caregivers experience engagement in their work, and specifically, how aspects of home healthcare work create meaning associated with employee engagement. Although much research on engagement has been conducted, little has addressed how individual differences such as worker orientation influence engagement, or how engagement is experienced within a caregiving context. The study is based on a qualitative study in two home homecare organisations in Denmark using a think-aloud data technique, interviews and observations. The analysis suggests caregivers experience meaning in three relatively distinct ways, depending on their work orientation. Specifically, the nature of engagement varies across caregivers oriented towards being 'nurturers', 'professionals', or 'workers', and the sources of engagement differ for each of these types of caregivers. The article contributes by (i) advancing our theoretical understanding of employee engagement by emphasising meaning creation and (ii) identifying factors that influence meaning creation and engagement of home health caregivers, which should consequently affect the quality of services provided home healthcare patients. © 2015 Nordic College of Caring Science.

  5. Civic Engagement and Gentrification Issues in Metropolitan Baltimore

    Science.gov (United States)

    Durington, Matthew; Maddox, Camee; Ruhf, Adrienne; Gass, Shana; Schwermer, Justin

    2009-01-01

    Since the fall of 2006 a number of Towson University students concentrating in the discipline of anthropology have been part of a civic engagement and service-learning project focusing on an historic African-American community in Baltimore. While the focus of the research project concentrates on the processes of gentrification, individual student…

  6. Temperature response of soil respiration is dependent on concentration of readily decomposable C

    Science.gov (United States)

    Larionova, A. A.; Yevdokimov, I. V.; Bykhovets, S. S.

    2007-12-01

    Temperature acclimation of soil organic matter (SOM) decomposition is one of the major uncertainties in predicting soil CO2 efflux associated with the increase in global mean temperature. A reasonable explanation for an apparent acclimation proposed by Davidson and colleagues (2006) based on Michaelis-Menten kinetics suggests that temperature sensitivity decreases when both maximal activity of respiratory enzymes (Vmax) and half-saturation constant (Ks) cancel each other upon temperature increase. We tested the hypothesis of the canceling effect by the mathematical simulation of data obtained in incubation experiments with forest and arable soils. Our data support the hypothesis and suggest that concentration of readily decomposable C substrate (as glucose equivalents) and temperature dependent substrate release are the important factors controlling temperature sensitivity of soil respiration. The highest temperature sensitivity of soil respiration was observed when substrate release was temperature dependent and C substrate concentration was much lower than Ks. Increase of substrate content to the half-saturation constant by glucose addition resulted in temperature acclimation associated with the canceling effect. Addition of the substrate to the level providing respiration at a maximal rate Vmax leads to the acclimation of the whole microbial community as such. However, growing microbial biomass was more sensitive to the temperature alterations. This study improves our understanding of the instability of temperature sensitivity of soil respiration under field conditions, attributing this phenomenon to changes in concentration of readily decomposable C substrate.

  7. Letrozole regulates actin cytoskeleton polymerization dynamics in a SRC-1 dependent manner in the hippocampus of mice.

    Science.gov (United States)

    Zhao, Yangang; Yu, Yanlan; Zhang, Yuanyuan; He, Li; Qiu, Linli; Zhao, Jikai; Liu, Mengying; Zhang, Jiqiang

    2017-03-01

    In the hippocampus, local estrogens (E 2 ) derived from testosterone that is catalyzed by aromatase play important roles in the regulation of hippocampal neural plasticity, but the underlying mechanisms remain unclear. The actin cytoskeleton contributes greatly to hippocampal synaptic plasticity; however, whether it is regulated by local E 2 and the related mechanisms remain to be elucidated. In this study, we first examined the postnatal developmental profiles of hippocampal aromatase and specific proteins responsible for actin cytoskeleton dynamics. Then we used aromatase inhibitor letrozole (LET) to block local E 2 synthesis and examined the changes of these proteins and steroid receptor coactivator-1 (SRC-1), the predominant coactivator for steroid nuclear receptors. Finally, SRC-1 specific RNA interference was used to examine the effects of SRC-1 on the expression of these actin remodeling proteins. The results showed a V-type profile for aromatase and increased profiles for actin cytoskeleton proteins in both male and female hippocampus without obvious sex differences. LET treatment dramatically decreased the F-actin/G-actin ratio, the expression of Rictor, phospho-AKT (ser473), Profilin-1, phospho-Cofilin (Ser3), and SRC-1 in a dose-dependent manner. In vitro studies demonstrated that LET induced downregulation of these proteins could be reversed by E 2 , and E 2 induced increase of these proteins were significantly suppressed by SRC-1 shRNA interference. These results for the first time clearly demonstrated that local E 2 inhibition could induce aberrant actin polymerization; they also showed an important role of SRC-1 in the mediation of local E 2 action on hippocampal synaptic plasticity by regulation of actin cytoskeleton dynamics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Influence of repeated permanent coloring and bleaching on ethyl glucuronide concentrations in hair from alcohol-dependent patients.

    Science.gov (United States)

    Crunelle, Cleo L; Yegles, Michel; De Doncker, Mireille; Dom, Geert; Cappelle, Delphine; Maudens, Kristof E; van Nuijs, Alexander L N; Covaci, Adrian; Neels, Hugo

    2015-02-01

    Ethyl glucuronide (EtG), a minor metabolite of alcohol, is used as a sensitive marker in hair to detect the retrospective consumption of alcohol. The proximal 0-3 cm hair segment is often used for analysis, providing information on alcohol consumption over the past 3 months. Using more distal segments would allow the detection of alcohol consumption over longer time periods, thereby addressing the chronicity of the consumption. In view of this, permanent coloring and bleaching were shown in vitro to alter EtG concentrations in hair, but no in vivo studies are available to prove or disprove this. To investigate the influence of repeated bleaching and permanent coloring on EtG concentrations in vivo and to assess the stability of EtG concentrations in distal compared to proximal hair segments. Hair samples from alcohol-dependent patients with uncolored/unbleached (N=4), permanent coloration (N=5) and bleached hair (N=5) were analyzed in two to six 3 cm long segments for EtG concentrations, and alcohol consumption and hair cosmetic treatments were assessed. We observed that hair bleaching and permanent coloring reduces EtG concentrations by 82±11% and 65±24%, respectively, with correlations between the number of cosmetic treatments and the decrease in EtG concentrations. EtG remained stable in untreated hair samples up to 18 cm. EtG is a sensitive marker to assess chronic alcohol consumption up to 18 months in alcohol-dependent patients with no cosmetic hair treatments. However, in alcohol-dependent patients who color or bleach their hair, care should be taken when interpreting EtG measurements. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. The Concentration Dependence of the (Delta)s Term in the Gibbs Free Energy Function: Application to Reversible Reactions in Biochemistry

    Science.gov (United States)

    Gary, Ronald K.

    2004-01-01

    The concentration dependence of (delta)S term in the Gibbs free energy function is described in relation to its application to reversible reactions in biochemistry. An intuitive and non-mathematical argument for the concentration dependence of the (delta)S term in the Gibbs free energy equation is derived and the applicability of the equation to…

  10. Tension-Induced Error Correction and Not Kinetochore Attachment Status Activates the SAC in an Aurora-B/C-Dependent Manner in Oocytes.

    Science.gov (United States)

    Vallot, Antoine; Leontiou, Ioanna; Cladière, Damien; El Yakoubi, Warif; Bolte, Susanne; Buffin, Eulalie; Wassmann, Katja

    2018-01-08

    Cell division with partitioning of the genetic material should take place only when paired chromosomes named bivalents (meiosis I) or sister chromatids (mitosis and meiosis II) are correctly attached to the bipolar spindle in a tension-generating manner. For this to happen, the spindle assembly checkpoint (SAC) checks whether unattached kinetochores are present, in which case anaphase onset is delayed to permit further establishment of attachments. Additionally, microtubules are stabilized when they are attached and under tension. In mitosis, attachments not under tension activate the so-named error correction pathway depending on Aurora B kinase substrate phosphorylation. This leads to microtubule detachments, which in turn activates the SAC [1-3]. Meiotic divisions in mammalian oocytes are highly error prone, with severe consequences for fertility and health of the offspring [4, 5]. Correct attachment of chromosomes in meiosis I leads to the generation of stretched bivalents, but-unlike mitosis-not to tension between sister kinetochores, which co-orient. Here, we set out to address whether reduction of tension applied by the spindle on bioriented bivalents activates error correction and, as a consequence, the SAC. Treatment of oocytes in late prometaphase I with Eg5 kinesin inhibitor affects spindle tension, but not attachments, as we show here using an optimized protocol for confocal imaging. After Eg5 inhibition, bivalents are correctly aligned but less stretched, and as a result, Aurora-B/C-dependent error correction with microtubule detachment takes place. This loss of attachments leads to SAC activation. Crucially, SAC activation itself does not require Aurora B/C kinase activity in oocytes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Cisplatin-resistant lung cancer cell–derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100–5p-dependent manner

    Directory of Open Access Journals (Sweden)

    Qin X

    2017-05-01

    Full Text Available Xiaobing Qin,1,2,* Shaorong Yu,1,3,* Leilei Zhou,1,4 Meiqi Shi,3 Yong Hu,1 Xiaoyue Xu,1 Bo Shen,1 Siwen Liu,1 Dali Yan,1 Jifeng Feng1,3 1Research Center for Clinical Oncology, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, 2Department of Oncology, Xuzhou First People’s Hospital, Xuzhou, 3Department of Oncology, Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, 4Department of Oncology, Affiliated Huai’an Hospital of Nanjing Medical University, Huai’an, Jiangsu, China *These authors have contributed equally to this work Abstract: Exosomes derived from lung cancer cells confer cisplatin (DDP resistance to other cancer cells. However, the underlying mechanism is still unknown. A549 resistance to DDP (A549/DDP was established. Microarray was used to analyze microRNA (miRNA expression profiles of A549 cells, A549/DDP cells, A549 exosomes, and A549/DDP exosomes. There was a strong correlation of miRNA profiles between exosomes and their maternal cells. A total of 11 miRNAs were significantly upregulated both in A549/DDP cells compared with A549 cells and in exosomes derived from A549/DDP cells in contrast to exosomes from A549 cells. A total of 31 downregulated miRNAs were also observed. miR-100–5p was the most prominent decreased miRNA in DDP-resistant exosomes compared with the corresponding sensitive ones. Downregulated miR-100–5p was proved to be involved in DDP resistance in A549 cells, and mammalian target of rapamycin (mTOR expression was reverse regulated by miR-100–5p. Exosomes confer recipient cells’ resistance to DDP in an exosomal miR-100–5p-dependent manner with mTOR as its potential target both in vitro and in vivo. Exosomes from DDP-resistant lung cancer cells A549 can alter other lung cancer cells’ sensitivity to DDP in exosomal miR-100–5p-dependent

  12. Macrophages migrate in an activation-dependent manner to chemokines involved in neuroinflammation

    NARCIS (Netherlands)

    Vogel, D.Y.S.; Heijnen, D.A.M.; Breur, M.; de Vries, H.E.; Tool, A.T.; Amor, S.; Dijkstra, C.D.

    2014-01-01

    Background: In neuroinflammatory diseases, macrophages can play a dual role in the process of tissue damage, depending on their activation status (M1 / M2). M1 macrophages are considered to exert damaging effects to neurons, whereas M2 macrophages are reported to aid regeneration and repair of

  13. Inorganic speciation of dissolved elements in seawater: the influence of pH on concentration ratios

    Directory of Open Access Journals (Sweden)

    Byrne Robert H

    2002-01-01

    Full Text Available Assessments of inorganic elemental speciation in seawater span the past four decades. Experimentation, compilation and critical review of equilibrium data over the past forty years have, in particular, considerably improved our understanding of cation hydrolysis and the complexation of cations by carbonate ions in solution. Through experimental investigations and critical evaluation it is now known that more than forty elements have seawater speciation schemes that are strongly influenced by pH. In the present work, the speciation of the elements in seawater is summarized in a manner that highlights the significance of pH variations. For elements that have pH-dependent species concentration ratios, this work summarizes equilibrium data (S = 35, t = 25°C that can be used to assess regions of dominance and relative species concentrations. Concentration ratios of complex species are expressed in the form log[A]/[B] = pH - C where brackets denote species concentrations in solution, A and B are species important at higher (A and lower (B solution pH, and C is a constant dependent on salinity, temperature and pressure. In the case of equilibria involving complex oxy-anions (MOx(OHy or hydroxy complexes (M(OHn, C is written as pKn = -log Kn or pKn* = -log Kn* respectively, where Kn and Kn* are equilibrium constants. For equilibria involving carbonate complexation, the constant C is written as pQ = -log(K2lKn [HCO3-] where K2l is the HCO3 - dissociation constant, Kn is a cation complexation constant and [HCO3-] is approximated as 1.9 × 10-3 molar. Equilibrium data expressed in this manner clearly show dominant species transitions, ranges of dominance, and relative concentrations at any pH.

  14. Ionic relaxation in PEO/PVDF-HFP-LiClO4 blend polymer electrolytes: dependence on salt concentration

    Science.gov (United States)

    Das, S.; Ghosh, A.

    2016-06-01

    In this paper, we have studied the effect of LiClO4 salt concentration on the ionic conduction and relaxation in poly ethylene oxide (PEO) and poly (vinylidene fluoride hexafluoropropylene) (PVDF-HFP) blend polymer electrolytes, in which the molar ratio of ethylene oxide segments to lithium ions (R  =  EO: Li) has been varied between 3 and 35. We have observed two phases in the samples containing low salt concentrations (R  >  9) and single phase in the samples containing high salt concentrations (R  ⩽  9). The scanning electron microscopic images indicate that there exists no phase separation in the blend polymer electrolytes. The temperature dependence of the ionic conductivity shows two slopes corresponding to high and low temperatures and follows Arrhenius relation for the samples containing low salt concentrations (R  >  9). The conductivity relaxation as well as the structural relaxation has been clearly observed at around 104 Hz and 106 Hz for these concentrations of the blended electrolytes. However, a single conductivity relaxation peak has been observed for the compositions with R  ⩽  9. The scaling of the conductivity spectra shows that the relaxation mechanism is independent of temperature, but depends on salt concentration.

  15. Adaptation of the Brazilian version of the Utrecht Work Engagement Scale

    NARCIS (Netherlands)

    Souza Vasquez, A; Dos Santos, E; Paico, E; Hurtz, C; Schaufeli, W.B.|info:eu-repo/dai/nl/073779563

    2015-01-01

    Engagement at work is a positive mental and dispositional state characterized by Vigor, Dedication and Concentration. The aim of this study was to adapt and get evidence of validity for the Brazilian version of the utrecht work engagement scale (UWES). Participated in the study 1167 workers between

  16. Dependence of samarium-soil interaction on samarium concentration: Implications for environmental risk assessment.

    Science.gov (United States)

    Ramírez-Guinart, Oriol; Salaberria, Aitor; Vidal, Miquel; Rigol, Anna

    2018-03-01

    The sorption and desorption behaviour of samarium (Sm), an emerging contaminant, was examined in soil samples at varying Sm concentrations. The obtained sorption and desorption parameters revealed that soil possessed a high Sm retention capacity (sorption was higher than 99% and desorption lower than 2%) at low Sm concentrations, whereas at high Sm concentrations, the sorption-desorption behaviour varied among the soil samples tested. The fractionation of the Sm sorbed in soils, obtained by sequential extractions, allowed to suggest the soil properties (pH and organic matter solubility) and phases (organic matter, carbonates and clay minerals) governing the Sm-soil interaction. The sorption models constructed in the present work along with the sorption behaviour of Sm explained in terms of soil main characteristics will allow properly assessing the Sm-soil interaction depending on the contamination scenario under study. Moreover, the sorption and desorption K d values of radiosamarium in soils were strongly correlated with those of stable Sm at low concentrations (r = 0.98); indicating that the mobility of Sm radioisotopes and, thus, the risk of radioactive Sm contamination can be predicted using data from low concentrations of stable Sm. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Borderline maintenance of erythrocyte 2,3-diphosphoglycerate concentrations in normoxic type 1 (insulin dependent) diabetic subjects.

    Science.gov (United States)

    Story, C J; Roberts, A P; Ryall, R G

    1986-02-01

    Erythrocyte 2,3-diphosphoglycerate and haemoglobin A1c concentrations were measured in 26 clinically normoxic patients with type 1 (insulin dependent) diabetes mellitus. The concentration of 2,3-diphosphoglycerate theoretically required to maintain normal erythrocyte oxygen delivery function in each subject was calculated and compared with the measured concentrations. In the majority of diabetic patients 2,3-diphosphoglycerate concentrations were sufficient to keep the erythrocyte oxygen dissociation curve within the normal range under otherwise normal blood conditions. There was, however, a minority of patients in which this was not true. It is concluded that the increased erythrocyte 2,3-diphosphoglycerate concentrations in clinically normoxic diabetic subjects are generally less than compensatory for the effect of haemoglobin A1c formation on the haemoglobin-oxygen dissociation curve.

  18. Concentration dependence of surface properties and molar volume of multicomponent system indium-tin-lead-bismuth

    Energy Technology Data Exchange (ETDEWEB)

    Dadashev, R; Kutuev, R [Complex Science Research Institute of the Science Academy of the Chechen Republic, 21 Staropromisl. shosse, Grozny 364096 (Russian Federation); Elimkhanov, D [Science Academy of the Chechen Republic (Russian Federation)], E-mail: edzhabrail@mail.ru

    2008-02-15

    The results of an experimental research of surface properties of the four-component system indium-tin-lead-bismuth are presented. The researches under discussion were carried out in a combined device in which the surface tension ({sigma}) is measured by the method of maximum pressure in a drop, and density ({rho}) is measured by advanced aerometry. Measurement errors are 0.7 % for surface tension measurement, and 0.2 % for density measurement. The study of the concentration dependence of {sigma} in this system has revealed the influence of the third and fourth components upon the characteristics of surface tension isotherms of the binary system indium-tin. It was found out that with an increase in the content of the third and fourth components the depth of the minimum on the surface tension isotherms of the indium-tin system {sigma} decreases. On the basis of the concentration dependence of the phenomenon of concentration bufferity is revealed. It is shown that despite the complex character, isotherms of {sigma} on beam sections of a multicomponent system do not contain qualitatively new features in comparison with the isotherms of these properties in lateral binary systems.

  19. Calcium-dependent but calmodulin-independent protein kinase from soybean

    International Nuclear Information System (INIS)

    Harmon, A.C.; Putnam-Evans, C.; Cormier, M.J.

    1987-01-01

    A calcium-dependent protein kinase activity from suspension-cultured soybean cells (Glycine max L. Wayne) was shown to be dependent on calcium but not calmodulin. The concentrations of free calcium required for half-maximal histone H1 phosphorylation and autophosphorylation were similar (≥ 2 micromolar). The protein kinase activity was stimulated 100-fold by ≥ 10 micromolar-free calcium. When exogenous soybean or bovine brain calmodulin was added in high concentration (1 micromolar) to the purified kinase, calcium-dependent and -independent activities were weakly stimulated (≤ 2-fold). Bovine serum albumin had a similar effect on both activities. The kinase was separated from a small amount of contaminating calmodulin by sodium dodecyl sulfate polyacrylamide gel electrophoresis. After renaturation the protein kinase autophosphorylated and phosphorylated histone H1 in a calcium-dependent manner. Following electroblotting onto nitrocellulose, the kinase bound 45 Ca 2+ in the presence of KCl and MgCl 2 , which indicated that the kinase itself is a high-affinity calcium-binding protein. Also, the mobility of one of two kinase bands in SDS gels was dependent on the presence of calcium. Autophosphorylation of the calmodulin-free kinase was inhibited by the calmodulin-binding compound N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7), showing that the inhibition of activity by W-7 is independent of calmodulin. These results show that soybean calcium-dependent protein kinase represents a new class of protein kinase which requires calcium but not calmodulin for activity

  20. Temperature response of soil respiration is dependent on concentration of readily decomposable C

    Directory of Open Access Journals (Sweden)

    A. A. Larionova

    2007-12-01

    Full Text Available Temperature acclimation of soil organic matter (SOM decomposition is one of the major uncertainties in predicting soil CO2 efflux associated with the increase in global mean temperature. A reasonable explanation for an apparent acclimation proposed by Davidson and colleagues (2006 based on Michaelis-Menten kinetics suggests that temperature sensitivity decreases when both maximal activity of respiratory enzymes (Vmax and half-saturation constant (Ks cancel each other upon temperature increase. We tested the hypothesis of the canceling effect by the mathematical simulation of data obtained in incubation experiments with forest and arable soils. Our data support the hypothesis and suggest that concentration of readily decomposable C substrate (as glucose equivalents and temperature dependent substrate release are the important factors controlling temperature sensitivity of soil respiration. The highest temperature sensitivity of soil respiration was observed when substrate release was temperature dependent and C substrate concentration was much lower than Ks. Increase of substrate content to the half-saturation constant by glucose addition resulted in temperature acclimation associated with the canceling effect. Addition of the substrate to the level providing respiration at a maximal rate Vmax leads to the acclimation of the whole microbial community as such. However, growing microbial biomass was more sensitive to the temperature alterations. This study improves our understanding of the instability of temperature sensitivity of soil respiration under field conditions, attributing this phenomenon to changes in concentration of readily decomposable C substrate.

  1. Confinement dependent chemotaxis in two-photon polymerized linear migration constructs with highly definable concentration gradients

    DEFF Research Database (Denmark)

    Hjortø, Gertrud Malene; Olsen, Mark Holm; Svane, Inge Marie

    2015-01-01

    Dendritic cell chemotaxis is known to follow chemoattractant concentration gradients through tissue of heterogeneous pore sizes, but the dependence of migration velocity on pore size and gradient steepness is not fully understood. We enabled chemotaxis studies for at least 42 hours at confinement...

  2. Berberine Improves Intestinal Motility and Visceral Pain in the Mouse Models Mimicking Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D Symptoms in an Opioid-Receptor Dependent Manner.

    Directory of Open Access Journals (Sweden)

    Chunqiu Chen

    Full Text Available Berberine and its derivatives display potent analgesic, anti-inflammatory and anticancer activity. Here we aimed at characterizing the mechanism of action of berberine in the gastrointestinal (GI tract and cortical neurons using animal models and in vitro tests.The effect of berberine was characterized in murine models mimicking diarrhea-predominant irritable bowel syndrome (IBS-D symptoms. Then the opioid antagonists were used to identify the receptors involved. Furthermore, the effect of berberineon opioid receptors expression was established in the mouse intestine and rat fetal cortical neurons.In mouse models, berberine prolonged GI transit and time to diarrhea in a dose-dependent manner, and significantly reduced visceral pain. In physiological conditions the effects of berberine were mediated by mu- (MOR and delta- (DOR opioid receptors; hypermotility, excessive secretion and nociception were reversed by berberine through MOR and DOR-dependent action. We also found that berberine increased the expression of MOR and DOR in the mouse bowel and rat fetal cortical neurons.Berberine significantly improved IBS-D symptoms in animal models, possibly through mu- and delta- opioid receptors. Berberine may become a new drug candidate for the successful treatment of IBS-D in clinical conditions.

  3. Blood lactate clearance after maximal exercise depends on active recovery intensity.

    Science.gov (United States)

    Devlin, J; Paton, B; Poole, L; Sun, W; Ferguson, C; Wilson, J; Kemi, O J

    2014-06-01

    High-intensity exercise is time-limited by onset of fatigue, marked by accumulation of blood lactate. This is accentuated at maximal, all-out exercise that rapidly accumulates high blood lactate. The optimal active recovery intensity for clearing lactate after such maximal, all-out exercise remains unknown. Thus, we studied the intensity-dependence of lactate clearance during active recovery after maximal exercise. We constructed a standardized maximal, all-out treadmill exercise protocol that predictably lead to voluntary exhaustion and blood lactate concentration>10 mM. Next, subjects ran series of all-out bouts that increased blood lactate concentration to 11.5±0.2 mM, followed by recovery exercises ranging 0% (passive)-100% of the lactate threshold. Repeated measurements showed faster lactate clearance during active versus passive recovery (P40%>passive recovery, Pexercise clears accumulated blood lactate faster than passive recovery in an intensity-dependent manner, with maximum clearance occurring at active recovery of 80% of lactate threshold.

  4. Interpersonal dependency and online gaming addiction.

    Science.gov (United States)

    Škařupová, Kateřina; Blinka, Lukas

    2016-03-01

    Background and aims The present study explores the relationship between social motivations and addiction to online gaming and if that possible connection can be explained by the personality traits responsible for social functioning. Methods We employ Bernstein's concept of interpersonal dependency to distinguish healthy dependency, dysfunctional detachment, and destructive overdependence, and Charlton and Danforth's conceptualisation of online gaming addiction and high engagement. An online questionnaire was administered to a self-nominated sample of 4,074 online gamers. Two regression models were constructed to separately explain gaming addiction and high engagement using social motivations to play, while controlling for age, gender, and time spent online. Results High scores on subscales measuring dysfunctional detachment and destructive overdependence were positively associated with online gaming addiction, while healthy dependency was negatively correlated with addiction scores. In contrast, the overall role of social motivation was negligible. Discussion People with healthy relationship profiles are less likely to develop problematic patterns of online gaming. High in-game engagement, although sharing some factors with addiction, was only poorly explained by the study variables, suggesting the mutual exclusiveness of addiction and engagement.

  5. Engagement and Retention in Outpatient Alcoholism Treatment for Women

    Science.gov (United States)

    Graff, Fiona S.; Morgan, Thomas J.; Epstein, Elizabeth E.; McCrady, Barbara S.; Cook, Sharon M.; Jensen, Noelle K.; Kelly, Shalonda

    2011-01-01

    Reviews of the dropout literature note significant attrition from addiction treatment. However, consistent predictors have not been identified and few studies have examined factors related to retention and engagement for women in gender-specific treatment. The current study consisted of 102 women and their partners randomized to individual or couples outpatient alcoholism treatment. Women attended more treatment sessions if they were assigned to individual treatment, older, had fewer symptoms of alcohol dependence, had more satisfying marital relationships, had spouses who drank, and had matched preference for treatment condition. Women were more engaged in treatment (i.e., completed more assigned homework) if they had fewer children at home, fewer alcohol dependence symptoms, later age of onset of alcohol diagnosis, more satisfying marital relationships, and spouses who accepted or encouraged their drinking. Results highlight important associations of treatment and relationship variables with treatment retention and engagement. PMID:19444731

  6. Concentration-dependent metabolic effects of metformin in healthy and Fanconi anemia lymphoblast cells.

    Science.gov (United States)

    Ravera, Silvia; Cossu, Vanessa; Tappino, Barbara; Nicchia, Elena; Dufour, Carlo; Cavani, Simona; Sciutto, Andrea; Bolognesi, Claudia; Columbaro, Marta; Degan, Paolo; Cappelli, Enrico

    2018-02-01

    Metformin (MET) is the drug of choice for patients with type 2 diabetes and has been proposed for use in cancer therapy and for treating other metabolic diseases. More than 14,000 studies have been published addressing the cellular mechanisms affected by MET. However, several in vitro studies have used concentrations of the drug 10-100-fold higher than the plasmatic concentration measured in patients. Here, we evaluated the biochemical, metabolic, and morphologic effects of various concentrations of MET. Moreover, we tested the effect of MET on Fanconi Anemia (FA) cells, a DNA repair genetic disease with defects in energetic and glucose metabolism, as well as on human promyelocytic leukemia (HL60) cell lines. We found that the response of wild-type cells to MET is concentration dependent. Low concentrations (15 and 150 µM) increase both oxidative phosphorylation and the oxidative stress response, acting on the AMPK/Sirt1 pathway, while the high concentration (1.5 mM) inhibits the respiratory chain, alters cell morphology, becoming toxic to the cells. In FA cells, MET was unable to correct the energetic/respiratory defect and did not improve the response to oxidative stress and DNA damage. By contrast, HL60 cells appear sensitive also at 150 μM. Our findings underline the importance of the MET concentration in evaluating the effect of this drug on cell metabolism and demonstrate that data obtained from in vitro experiments, that have used high concentrations of MET, cannot be readily translated into improving our understanding of the cellular effects of metformin when used in the clinical setting. © 2017 Wiley Periodicals, Inc.

  7. Mannerisms of the Elderly and Approaches to Rapport.

    Science.gov (United States)

    French, Warren A.; And Others

    1980-01-01

    Many older adults react to old age with empirically identified distinguishable mannerisms. Using these mannerisms, or behavior patterns, as a basis for rapport, gerontologists can: (1) uncover causes of adjustment problems; (2) assess seriousness of problems; and (3) implement counseling suggestions. (Author/JAC)

  8. NARRATIVE PERSPECTIVE MEDIATED BY MANNER OF MOTION VERBS

    Directory of Open Access Journals (Sweden)

    Olesea BODEAN-VOZIAN

    2016-12-01

    Full Text Available There is typological variation in the way languages encode manner as an element of a motion event. Languages like English view it as relevant, and the lexicalization of the variety of ways to move results in a rich class of motion verbs, contrary to other types of languages, like Romanian, which leave the manner element to be encoded by verbids or adverbs (for these reasons some linguists refer to the first type as manner-rich and second type as manner-poor languages. Still, several studies contrasting typologically different languages showed that languages of the latter type are not so poor in manner-of-motion verbs. The question then might rather be: which manner components are more likely to be lexicalized?For research purposes, we distinguish manner in terms of objective elements (medium, speed or intensity and subjective elements (attitude, intention. The aim of the study is to focus on the manner-of-motion verbs that embed an evaluative or qualitative dimension of motion and to examine the way these verbs encode somebody’s perspective in a narrative. The first question in such a case is whose evaluation or point of view is being represented. The second one is how the subjective point of view (narrative perspective mediated through manner-of-motion verbs in an English narrative (The Lord of the Rings, by J.R.R. Tolkien is translated into Romanian, supposedly a manner-poor or low-manner language.PERSPECTIVA NARATIVĂ MEDIATĂ DE VERBELE DE MIŞCARE DE MODExistă o variaţie tipologică în felul în care limbile codifică modul ca element al unui eveniment de mişcare. Limbile precum engleza îl percep drept unul relevant, iar lexicalizarea gamei de mijloace de redare a mişcării a dat naştere unei clase bogate de verbe de mişcare, contrar altor tipuri de limbi, aşa ca româna, în care elementul ce redă modul este codificat de gerunziu sau adverbe. Din aceasta cauză, unii lingvişti numesc primul tip limbi bogate în verbe de mod (

  9. Reading Motivation and Engagement at a Rural Georgia High School

    Science.gov (United States)

    Winfree, Linda

    2013-01-01

    As college and workplace success becomes increasingly dependent on reading, parents and educators have become more interested in how to engage students in reading. Teachers at a rural Georgia high school have reported that students are reluctant to engage in academic reading. Guided by previous research on the factors that promote or discourage…

  10. Amyloid β oligomers induce interleukin-1β production in primary microglia in a cathepsin B- and reactive oxygen species-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Taneo, Jun; Adachi, Takumi [Department of Animal Development and Physiology, Kyoto University, Yoshida-Konoe, Sakyo, Kyoto 606-8501 (Japan); Yoshida, Aiko; Takayasu, Kunio [Responses to Environmental Signals and Stresses, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe, Sakyo, Kyoto, Kyoto 606-8501 (Japan); Takahara, Kazuhiko, E-mail: ktakahar@zoo.zool.kyoto-u.ac.jp [Department of Animal Development and Physiology, Kyoto University, Yoshida-Konoe, Sakyo, Kyoto 606-8501 (Japan); Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST), Tokyo 102-0081 (Japan); Inaba, Kayo [Department of Animal Development and Physiology, Kyoto University, Yoshida-Konoe, Sakyo, Kyoto 606-8501 (Japan); Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST), Tokyo 102-0081 (Japan)

    2015-03-13

    Amyloid β (Aβ) peptide, a causative agent of Alzheimer's disease, forms two types of aggregates: oligomers and fibrils. These aggregates induce inflammatory responses, such as interleukin-1β (IL-1β) production by microglia, which are macrophage-like cells located in the brain. In this study, we examined the effect of the two forms of Aβ aggregates on IL-1β production in mouse primary microglia. We prepared Aβ oligomer and fibril from Aβ (1–42) peptide in vitro. We analyzed the characteristics of these oligomers and fibrils by electrophoresis and atomic force microscopy. Interestingly, Aβ oligomers but not Aβ monomers or fibrils induced robust IL-1β production in the presence of lipopolysaccharide. Moreover, Aβ oligomers induced endo/phagolysosome rupture, which released cathepsin B into the cytoplasm. Aβ oligomer-induced IL-1β production was inhibited not only by the cathepsin B inhibitor CA-074-Me but also by the reactive oxygen species (ROS) inhibitor N-acetylcysteine. Random chemical crosslinking abolished the ability of the oligomers to induce IL-1β. Thus, multimerization and fibrillization causes Aβ oligomers to lose the ability to induce IL-1β. These results indicate that Aβ oligomers, but not fibrils, induce IL-1β production in primary microglia in a cathepsin B- and ROS-dependent manner. - Highlights: • We prepared amyloid β (Aβ) fibrils with minimum contamination of Aβ oligomers. • Primary microglia (MG) produced IL-1β in response to Aβ oligomers, but not fibrils. • Only Aβ oligomers induced leakage of cathepsin B from endo/phagolysosomes. • IL-1β production in response to Aβ oligomers depended on both cathepsin B and ROS. • Crosslinking reduced the ability of the Aβ oligomers to induce IL-1β from MG.

  11. Dependence of Initial Oxygen Concentration on Ozone Yield Using Inductive Energy Storage System Pulsed Power Generator

    Science.gov (United States)

    Go, Tomio; Tanaka, Yasushi; Yamazaki, Nobuyuki; Mukaigawa, Seiji; Takaki, Koichi; Fujiwara, Tamiya

    Dependence of initial oxygen concentration on ozone yield using streamer discharge reactor driven by an inductive energy storage system pulsed power generator is described in this paper. Fast recovery type diodes were employed as semiconductor opening switch to interrupt a circuit current within 100 ns. This rapid current change produced high-voltage short pulse between a secondary energy storage inductor. The repetitive high-voltage short pulse was applied to a 1 mm diameter center wire electrode placed in a cylindrical pulse corona reactor. The streamer discharge successfully occurred between the center wire electrode and an outer cylinder ground electrode of 2 cm inner diameter. The ozone was produced with the streamer discharge and increased with increasing pulse repetition rate. The ozone yield changed in proportion to initial oxygen concentration contained in the injected gas mixture at 800 ns forward pumping time of the current. However, the decrease of the ozone yield by decreasing oxygen concentration in the gas mixture at 180 ns forward pumping time of the current was lower than the decrease at 800 ns forward pumping time of the current. This dependence of the initial oxygen concentration on ozone yield at 180 ns forward pumping time is similar to that of dielectric barrier discharge reactor.

  12. Radiation-induced strand-breaks and DNA-protein crosslinks depend predominantly on the dose, oxygen concentration and repair time

    International Nuclear Information System (INIS)

    Wheeler, K.T.; Miyagi, Y.; Zhang, H.

    1995-01-01

    It has been known for many years that the DNA damage produced by ionizing radiation depends upon the oxygen concentration around the DNA. For example, the number of DNA strand-breaks (SBs) formed per unit dose decreases at low oxygen concentrations, and the number of DNA-protein crosslinks formed per unit dose increases at low oxygen concentrations. If radiation-induced SBs and DPCs are to be useful for detecting and/or quantifying hypoxic cells in solid tumors, the formation of these lesions must depend predominantly on the oxygen concentration around the DNA. All other physical, biological, and physiological factors must either be controllable or have little influence on the assay used to measure these lesions. This paper is a summary of the authors' recent experiments to determine if the radiation-induced SBs and DPCs measured by alkaline elution may be used to estimate the hypoxic fraction or fractional hypoxic volume of solid tumors

  13. Smurf2 E3 ubiquitin ligase modulates proliferation and invasiveness of breast cancer cells in a CNKSR2 dependent manner.

    Science.gov (United States)

    David, Diana; Jagadeeshan, Sankar; Hariharan, Ramkumar; Nair, Asha Sivakumari; Pillai, Radhakrishna Madhavan

    2014-01-01

    Smurf2 is a member of the HECT family of E3 ubiquitin ligases that play important roles in determining the competence of cells to respond to TGF- β/BMP signaling pathway. However, besides TGF-β/BMP pathway, Smurf2 regulates a repertoire of other signaling pathways ranging from planar cell polarity during embryonic development to cell proliferation, migration, differentiation and senescence. Expression of Smurf2 is found to be dysregulated in many cancers including breast cancer. The purpose of the present study is to examine the effect of Smurf2 knockdown on the tumorigenic potential of human breast cancer cells emphasizing more on proliferative signaling pathway. siRNAs targeting different regions of the Smurf2 mRNA were employed to knockdown the expression of Smurf2. The biological effects of synthetic siRNAs on human breast cancer cells were investigated by examining the cell proliferation, migration, invasion, focus formation, anchorage-independent growth, cell cycle arrest, and cell cycle and cell proliferation related protein expressions upon Smurf2 silencing. Smurf2 silencing in human breast cancer cells resulted in a decreased focus formation potential and clonogenicity as well as in vitro cell migration/invasion capabilities. Moreover, knockdown of Smurf2 suppressed cell proliferation. Cell cycle analysis showed that the anti-proliferative effect of Smurf2 siRNA was mediated by arresting cells in the G0/G1 phase, which was caused by decreased expression of cyclin D1and cdk4, followed by upregulation p21 and p27. Furthermore, we demonstrated that silencing of Smurf2 downregulated the proliferation of breast cancer cells by modulating the PI3K- PTEN-AKT-FoxO3a pathway via the scaffold protein CNKSR2 which is involved in RAS-dependent signaling pathways. The present study provides the first evidence that silencing Smurf2 using synthetic siRNAs can regulate the tumorigenic properties of human breast cancer cells in a CNKSR2 dependent manner. Our results

  14. Cisplatin triggers apoptotic or nonapoptotic cell death in Fanconi anemia lymphoblasts in a concentration-dependent manner

    NARCIS (Netherlands)

    Ferrer, M; Izeboud, T; Ferreira, CG; Span, SW; Giaccone, G; Kruyt, FAE

    2003-01-01

    Cells derived from Fanconi anemia (FA) patients are hypersensitive for cross-linking agents, such as cisplatin, that are potent inducers of programmed cell death (PCD). Here, we studied cisplatin hypersensitivity in FA in relation to the mechanism of PCD in lymphoblastoid cells representing FA

  15. Aesthetic Engagement, Ecosophy C, and Ecological Appreciation

    Directory of Open Access Journals (Sweden)

    Cheng Xiangzhan

    2013-01-01

    Full Text Available With the aim of healing the earth and sustain a healthy ecosystem for all life forms, not humankind alone, ecoaesthetics emerges as a critique of Enlightenment mentality and of modern aesthetics as it is embodied in it. This mentality contributes greatly to the global ecological crisis and to other problem areas, such as population, economic, political and religious ones. In my understanding of aesthetics, ecoaesthetics is defined as the theory of ecological aesthetic appreciation.[1] With ecoaesthetics as my research horizon, there are at least two reasons for me to pay special attention to American philosopher Arnold Berleant’s conception of aesthetic engagement and his aesthetic theory based on it, an aesthetics of engagement. The first is our shared theme, which is the critique of modern aesthetics. The second reason is more complex for it involves the crucial question of the proper manner of aesthetic appreciation. From the perspective of ecoaesthetics, the contemplation of objects by a separated perceiver, an approach that is based on the modern philosophical dualism of subject and object, is unsatisfactory and inadequate. Berleant’s aesthetic engagement is a more satisfactory account of appreciation that is aesthetic and ecological. This emphasizes the ecological continuity or interrelatedness between the human appreciator and objects. Of course, any theory can occasion critique and development. Based on Berleant’s idea of aesthetic engagement, I would like to propose Ecosophy C. This can be contrasted with Ecosophy T proposed by the Norwegian, Arne Naess, and with traditional Chinese aesthetic wisdom. In contrast with these, I would like to develop my own view of ecological understanding. In order to construct a more comprehensive and reasonable ecoaesthetics, my Ecosophy C contains eight points that are crucial in building an ecological model of aesthetic appreciation for this period of ecological crisis.

  16. 48 CFR 1371.101 - Inspection and manner of doing work.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Inspection and manner of... DEPARTMENT SUPPLEMENTAL REGULATIONS ACQUISITIONS INVOLVING SHIP CONSTRUCTION AND SHIP REPAIR Provisions and Clauses 1371.101 Inspection and manner of doing work. Insert clause 1352.271-70, Inspection and Manner of...

  17. Student Engagement

    DEFF Research Database (Denmark)

    Conduit, Jodie; Karpen, Ingo; Farrelly, Francis

    2017-01-01

    system (the university), the narrow service system (the course), and the individual dyadic level of engagement (the student-lecturer interaction). These findings could be further considered and empirically tested in other engagement contexts (e.g. employee engagement, customer engagement).......Universities are seeking to actively and strategically manage student engagement through providing opportunities for students to interact and engage with the institution on a range of levels and in different ways. However, this increasingly complex and multi-layered nature of student engagement...... within a tertiary education environment is not well understood. Through qualitative focus groups and a series of interviews with undergraduate and postgraduate students, this study explores and articulates the cognitive, emotional, behavioural and social dimensions of engagement that depict the nature...

  18. The effect of emotions, promotion vs. prevention focus, and feedback on cognitive engagement

    Directory of Open Access Journals (Sweden)

    Wytykowska Agata

    2015-09-01

    Full Text Available The purpose of the study was to explore the role of emotions, promotion-prevention orientation and feedback on cognitive engagement. In the experiment participants had the possibility to engage in a categorization task thrice. After the first categorization all participants were informed that around 75% of their answers were correct. After the second categorization, depending on the experimental condition, participants received feedback either about success or failure. Involvement in the third categorization was depended on participants’ decision whether to take part in it or not. Each time, before and after categorization, the emotional state was assessed. Results showed that promotion orientation predicted experiencing curiosity before the task, which in turn led to a higher cognitive engagement in the first categorization. Promotion and prevention orientation moderated the type of emotional response to positive feedback. Promotion orientation also predicted cognitive engagement after the feedback of success was provided. Generally results confirmed the positive effect of positive emotions as well as promotion orientation on cognitive engagement.

  19. Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure

    International Nuclear Information System (INIS)

    Menelaou, Evdokia; Paul, Latoya T.; Perera, Surangi N.; Svoboda, Kurt R.

    2015-01-01

    Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMNs). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30 μM). Previous work showed that the paralytic mutant zebrafish known as sofa potato exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. - Highlights: • Embryonic nicotine exposure can specifically affect secondary motoneuron axons in a dose-dependent manner.

  20. Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure

    Energy Technology Data Exchange (ETDEWEB)

    Menelaou, Evdokia; Paul, Latoya T. [Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803 (United States); Perera, Surangi N. [Joseph J. Zilber School of Public Health, University of Wisconsin — Milwaukee, Milwaukee, WI 53205 (United States); Svoboda, Kurt R., E-mail: svobodak@uwm.edu [Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803 (United States); Joseph J. Zilber School of Public Health, University of Wisconsin — Milwaukee, Milwaukee, WI 53205 (United States)

    2015-04-01

    Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMNs). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30 μM). Previous work showed that the paralytic mutant zebrafish known as sofa potato exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. - Highlights: • Embryonic nicotine exposure can specifically affect secondary motoneuron axons in a dose-dependent manner.

  1. Restoring polyamines protects from age-induced memory impairment in an autophagy-dependent manner

    NARCIS (Netherlands)

    Gupta, V.K.; Scheunemann, L.; Eisenberg, T.; Mertel, S.; Bhukel, A.; Koemans, T.S.; Kramer, J.M.; Liu, K.S.; Schroeder, S.; Stunnenberg, H.G.; Sinner, F.; Magnes, C.; Pieber, T.R.; Dipt, S.; Fiala, A.; Schenck, A.; Schwaerzel, M.; Madeo, F.; Sigrist, S.J.

    2013-01-01

    Age-dependent memory impairment is known to occur in several organisms, including Drosophila, mouse and human. However, the fundamental cellular mechanisms that underlie these impairments are still poorly understood, effectively hampering the development of pharmacological strategies to treat the

  2. Unexpected T cell regulatory activity of anti-histone H1 autoantibody: Its mode of action in regulatory T cell-dependent and -independent manners

    Energy Technology Data Exchange (ETDEWEB)

    Takaoka, Yuki [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Kawamoto, Seiji, E-mail: skawa@hiroshima-u.ac.jp [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Katayama, Akiko [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Nakano, Toshiaki [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Yamanaka, Yasushi; Takahashi, Miki [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Shimada, Yayoi; Chiang, Kuei-Chen [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Ohmori, Naoya [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Faculty of Nursing, Josai International University, Togane (Japan); Aki, Tsunehiro [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Goto, Takeshi; Sato, Shuji [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Faculty of Nursing, Josai International University, Togane (Japan); Goto, Shigeru [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Iwao Hospital, Yufuin (Japan); Chen, Chao-Long [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Ono, Kazuhisa [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan)

    2013-02-08

    Highlights: ► Anti-histone H1 autoantibody (anti-H1) acts on T cells to inhibit their activation. ► Anti-H1 suppresses T cell activation in Treg cell-dependent and -independent manners. ► Suboptimal dose of anti-H1 enhances suppressor function of Treg cells. ► High dose of anti-H1 directly inhibits T cell receptor signaling. -- Abstract: Induction of anti-nuclear antibodies against DNA or histones is a hallmark of autoimmune disorders, but their actual contribution to disease predisposition remains to be clarified. We have previously reported that autoantibodies against histone H1 work as a critical graft survival factor in a rat model of tolerogeneic liver transplantation. Here we show that an immunosuppressive anti-histone H1 monoclonal antibody (anti-H1 mAb) acts directly on T cells to inhibit their activation in response to T cell receptor (TCR) ligation. Intriguingly, the T cell activation inhibitory activity of anti-H1 mAb under suboptimal dosages required regulatory T (Treg) cells, while high dose stimulation with anti-H1 mAb triggered a Treg cell-independent, direct negative regulation of T cell activation upon TCR cross-linking. In the Treg cell-dependent mode of immunosuppressive action, anti-H1 mAb did not induce the expansion of CD4{sup +}Foxp3{sup +} Treg cells, but rather potentiated their regulatory capacity. These results reveal a previously unappreciated T cell regulatory role of anti-H1 autoantibody, whose overproduction is generally thought to be pathogenic in the autoimmune settings.

  3. Unexpected T cell regulatory activity of anti-histone H1 autoantibody: Its mode of action in regulatory T cell-dependent and -independent manners

    International Nuclear Information System (INIS)

    Takaoka, Yuki; Kawamoto, Seiji; Katayama, Akiko; Nakano, Toshiaki; Yamanaka, Yasushi; Takahashi, Miki; Shimada, Yayoi; Chiang, Kuei-Chen; Ohmori, Naoya; Aki, Tsunehiro; Goto, Takeshi; Sato, Shuji; Goto, Shigeru; Chen, Chao-Long; Ono, Kazuhisa

    2013-01-01

    Highlights: ► Anti-histone H1 autoantibody (anti-H1) acts on T cells to inhibit their activation. ► Anti-H1 suppresses T cell activation in Treg cell-dependent and -independent manners. ► Suboptimal dose of anti-H1 enhances suppressor function of Treg cells. ► High dose of anti-H1 directly inhibits T cell receptor signaling. -- Abstract: Induction of anti-nuclear antibodies against DNA or histones is a hallmark of autoimmune disorders, but their actual contribution to disease predisposition remains to be clarified. We have previously reported that autoantibodies against histone H1 work as a critical graft survival factor in a rat model of tolerogeneic liver transplantation. Here we show that an immunosuppressive anti-histone H1 monoclonal antibody (anti-H1 mAb) acts directly on T cells to inhibit their activation in response to T cell receptor (TCR) ligation. Intriguingly, the T cell activation inhibitory activity of anti-H1 mAb under suboptimal dosages required regulatory T (Treg) cells, while high dose stimulation with anti-H1 mAb triggered a Treg cell-independent, direct negative regulation of T cell activation upon TCR cross-linking. In the Treg cell-dependent mode of immunosuppressive action, anti-H1 mAb did not induce the expansion of CD4 + Foxp3 + Treg cells, but rather potentiated their regulatory capacity. These results reveal a previously unappreciated T cell regulatory role of anti-H1 autoantibody, whose overproduction is generally thought to be pathogenic in the autoimmune settings

  4. Temperature dependence of the short-range order parameter and the concentration dependence of the order disorder temperature for Ni-Pt and Ni-Fe systems in the improved statistical pseudopotential approximation

    International Nuclear Information System (INIS)

    Khwaja, F.A.

    1980-08-01

    The calculations for the temperature dependence of the first shell short-range order (SRO) parameter for Ni 3 Fe using the cubic approximation of Tahir Kheli, and the concentration dependence of order-disorder temperature Tsub(c) for Ni-Fe and Ni-Pt systems using the linear approximation, have been carried out in the framework of pseudopotential theory. It is shown that the cubic approximation yields a good agreement between the theoretical prediction of the α 1 and the experimental data. Results for the concentration dependence of the Tsub(c) show that improvements in the statistical pseudo-potential approach are essential to achieve a good agreement with experiment. (author)

  5. Interpersonal dependency and online gaming addiction

    Science.gov (United States)

    Škařupová, Kateřina; Blinka, Lukas

    2016-01-01

    Background and aims The present study explores the relationship between social motivations and addiction to online gaming and if that possible connection can be explained by the personality traits responsible for social functioning. Methods We employ Bernstein’s concept of interpersonal dependency to distinguish healthy dependency, dysfunctional detachment, and destructive overdependence, and Charlton and Danforth’s conceptualisation of online gaming addiction and high engagement. An online questionnaire was administered to a self-nominated sample of 4,074 online gamers. Two regression models were constructed to separately explain gaming addiction and high engagement using social motivations to play, while controlling for age, gender, and time spent online. Results High scores on subscales measuring dysfunctional detachment and destructive overdependence were positively associated with online gaming addiction, while healthy dependency was negatively correlated with addiction scores. In contrast, the overall role of social motivation was negligible. Discussion People with healthy relationship profiles are less likely to develop problematic patterns of online gaming. High in-game engagement, although sharing some factors with addiction, was only poorly explained by the study variables, suggesting the mutual exclusiveness of addiction and engagement. PMID:26690326

  6. Concentration and length dependence of DNA looping in transcriptional regulation.

    Directory of Open Access Journals (Sweden)

    Lin Han

    2009-05-01

    Full Text Available In many cases, transcriptional regulation involves the binding of transcription factors at sites on the DNA that are not immediately adjacent to the promoter of interest. This action at a distance is often mediated by the formation of DNA loops: Binding at two or more sites on the DNA results in the formation of a loop, which can bring the transcription factor into the immediate neighborhood of the relevant promoter. These processes are important in settings ranging from the historic bacterial examples (bacterial metabolism and the lytic-lysogeny decision in bacteriophage, to the modern concept of gene regulation to regulatory processes central to pattern formation during development of multicellular organisms. Though there have been a variety of insights into the combinatorial aspects of transcriptional control, the mechanism of DNA looping as an agent of combinatorial control in both prokaryotes and eukaryotes remains unclear. We use single-molecule techniques to dissect DNA looping in the lac operon. In particular, we measure the propensity for DNA looping by the Lac repressor as a function of the concentration of repressor protein and as a function of the distance between repressor binding sites. As with earlier single-molecule studies, we find (at least two distinct looped states and demonstrate that the presence of these two states depends both upon the concentration of repressor protein and the distance between the two repressor binding sites. We find that loops form even at interoperator spacings considerably shorter than the DNA persistence length, without the intervention of any other proteins to prebend the DNA. The concentration measurements also permit us to use a simple statistical mechanical model of DNA loop formation to determine the free energy of DNA looping, or equivalently, the for looping.

  7. The effect of a concentration-dependent viscosity on particle transport in a channel flow with porous walls

    KAUST Repository

    Herterich, James G.

    2014-02-02

    The transport of a dilute suspension of particles through a channel with porous walls, accounting for the concentration dependence of the viscosity, is analyzed. In particular, we study two cases of fluid permeation through the porous channel walls: (1) at a constant flux and (2) dependent on the pressure drop across the wall. We also consider the effect of mixing the suspension first compared with point injection by considering inlet concentration distributions of different widths. We find that a pessimal inlet distribution width exists that maximizes the required hydrodynamic pressure for a constant fluid influx. The effect of an external hydrodynamic pressure, to compensate for the reduced transmembrane pressure difference due to osmotic pressure, is investigated. © 2014 American Institute of Chemical Engineers.

  8. Buprenorphine from detox and beyond: preliminary evaluation of a pilot program to increase heroin dependent individuals' engagement in a full continuum of care.

    Science.gov (United States)

    Donovan, Dennis M; Knox, Patricia C; Skytta, Jenny A F; Blayney, Jessica A; DiCenzo, Jessica

    2013-04-01

    Absence of successful transition to post-detoxification treatment leads to high rates of relapse among detoxified heroin users. The present study evaluated a pilot buprenorphine treatment program (BTP). Heroin dependent individuals were inducted onto buprenorphine/naloxone in detox, maintained while transitioning through an intensive inpatient program (IIP), and gradually tapered off medication over 5 months of outpatient (OP) treatment. Compared to programmatic indicators of treatment engagement in the year prior to BTP implementation, referrals from detox to IIP, entry into and completion of IIP and subsequent OP, and days in OP treatment increased substantially. BTP completers, compared to non-completers, viewed abstinence as more difficult and as requiring more assistance to achieve, were less likely to be current cocaine and alcohol users or to have relapsed during the course of treatment. Although preliminary and in need of replication, initial adjunctive use of buprenorphine in an abstinence-based continuum of care may improve post-detoxification treatment entry, engagement, and completion. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Moderate exercise during pregnancy in Wistar rats alters bone and body composition of the adult offspring in a sex-dependent manner.

    Directory of Open Access Journals (Sweden)

    Brielle V Rosa

    Full Text Available Exercise during pregnancy may have long-lasting effects on offspring health. Musculoskeletal growth and development, metabolism, and later-life disease risk can all be impacted by the maternal environment during pregnancy. The skeleton influences glucose handling through the actions of the bone-derived hormone osteocalcin. The purpose of this study was to test the effects of moderate maternal exercise during pregnancy on the bone and body composition of the offspring in adult life, and to investigate the role of osteocalcin in these effects. Groups of pregnant Wistar rats either performed bipedal standing exercise to obtain food/water throughout gestation but not lactation, or were fed conventionally. Litters were reduced to 8/dam and pups were raised to maturity under control conditions. Whole body dual-energy x-ray absorptiometry, and ex vivo peripheral quantitative computed tomography scans of the right tibia were performed. At study termination blood and tissue samples were collected. Serum concentrations of fully and undercarboxylated osteocalcin were measured, and the relative expression levels of osteocalcin, insulin receptor, Forkhead box transcription factor O1, and osteotesticular protein tyrosine phosphatase mRNA were quantified. Body mass did not differ between the offspring of exercised and control dams, but the male offspring of exercised dams had a greater % fat and lower % lean than controls (p=0.001 and p=0.0008, respectively. At the mid-tibial diaphysis, offspring of exercised dams had a lower volumetric bone mineral density than controls (p=0.01 and in the male offspring of exercised dams the bone: muscle relationship was fundamentally altered. Serum concentrations of undercarboxylated osteocalcin were significantly greater in the male offspring of exercised dams than in controls (p=0.02; however, the relative expression of the measured genes did not differ between groups. These results suggest that moderate exercise during

  10. Protein kinase C interaction with calcium: a phospholipid-dependent process.

    LENUS (Irish Health Repository)

    Bazzi, M D

    1990-08-21

    The calcium-binding properties of calcium- and phospholipid-dependent protein kinase C (PKC) were investigated by equilibrium dialysis in the presence and the absence of phospholipids. Calcium binding to PKC displayed striking and unexpected behavior; the free proteins bound virtually no calcium at intracellular calcium concentrations and bound limited calcium (about 1 mol\\/mol of PKC) at 200 microM calcium. However, in the presence of membranes containing acidic phospholipids, PKC bound at least eight calcium ions per protein. The presence of 1 microM phorbol dibutyrate (PDBu) in the dialysis buffer had little effect on these calcium-binding properties. Analysis of PKC-calcium binding by gel filtration under equilibrium conditions gave similar results; only membrane-associated PKC bound significant amounts of calcium. Consequently, PKC is a member of what may be a large group of proteins that bind calcium in a phospholipid-dependent manner. The calcium concentrations needed to induce PKC-membrane binding were similar to those needed for calcium binding (about 40 microM calcium at the midpoint). However, the calcium concentration required for PKC-membrane binding was strongly influenced by the phosphatidylserine composition of the membranes. Membranes with higher percentages of phosphatidylserine required lower concentrations of calcium. These properties suggested that the calcium sites may be generated at the interface between PKC and the membrane. Calcium may function as a bridge between PKC and phospholipids. These studies also suggested that calcium-dependent PKC-membrane binding and PKC function could be regulated by a number of factors in addition to calcium levels and diacylglycerol content of the membrane.

  11. CTRP3 is a novel biomarker for diabetic retinopathy and inhibits HGHL-induced VCAM-1 expression in an AMPK-dependent manner.

    Directory of Open Access Journals (Sweden)

    Zheyi Yan

    Full Text Available Diabetic retinopathy (DR is a severe complication of chronic diabetes. The C1q/TNF-related protein family (CTRPs has been demonstrated to exert protective effects against obesity and atherosclerosis in animal studies. Heretofore, the association between circulating CTRPs and DR patients has been unexplored. In the current study, we attempt to define this association, as well as the effect of CTRPs upon DR pathophysiology.The present investigation is a case control study that enrolled control subjects and type 2 diabetes mellitus (T2DM patients diagnosed with DR. Serum CTRPs and sVACM-1 were determined by ELISA.Serum CTRP3 and CTRP5 levels were markedly decreased in patients with T2DM compared to controls (p<0.05 and inversely associated with T2DM. Furthermore, mutivariate regression and ROC analysis revealed CTRP3 deficiency, not CTRP5, was associated with proliferative diabetic retinopathy (PDR. Spearman's rank correlation assay demonstrated an inverse association between CTRP3 and sVCAM-1. Finally, exogenous CTRP3 administration attenuated high glucose high lipid (HGHL-induced VCAM-1 production in an AMPK-dependent manner in cultured human retinal microvascular endothelial cells (HRMECs.CTRP3 may serve as a novel biomarker for DR severity. CTRP3 may represent a future novel therapeutic against DR, a common ocular complication of diabetes.

  12. a Study of the Concentration Dependence of Macromolecular Diffusion Using Photon Correlation Spectroscopy.

    Science.gov (United States)

    Marlowe, Robert Lloyd

    The dynamic light scattering technique of photon correlation spectroscopy has been used to investigate the dependence of the mutual diffusion coefficient of a macromolecular system upon concentration. The first part of the research was devoted to the design and construction of a single-clipping autocorrelator based on newly-developed integrated circuits. The resulting 128 channel instrument can perform real time autocorrelation for sample time intervals >(, )10 (mu)s, and batch processed autocorrelation for intervals down to 3 (mu)s. An improved design for a newer, all-digital autocorrelator is given. Homodyne light scattering experiments were then undertaken on monodisperse solutions of polystyrene spheres. The single-mode TEM(,oo) beam of an argon-ion laser ((lamda) = 5145 (ANGSTROM)) was used as the light source; all solutions were studied at room temperature. The scattering angle was varied from 30(DEGREES) to 110(DEGREES). Excellent agreement with the manufacturer's specification for the particle size was obtained from the photon correlation studies. Finally, aqueous solutions of the globular protein ovalbumin, ranging in concentration from 18.9 to 244.3 mg/ml, were illuminated under the same conditions of temperature and wavelength as before; the homodyne scattered light was detected at a fixed scattering angle of 30(DEGREES). The single-clipped photocount autocorrelation function was analyzed using the homodyne exponential integral method of Meneely et al. The resulting diffusion coefficients showed a general linear dependence upon concentration, as predicted by the generalized Stokes-Einstein equation. However, a clear peak in the data was evident at c (TURNEQ) 100 mg/ml, which could not be explained on the basis of a non -interacting particle theory. A semi-quantitative approach based on the Debye-Huckel theory of electrostatic interactions is suggested as the probable cause for the peak's rise, and an excluded volume effect for its decline.

  13. Tyrosine nitration in blood vessels occurs with increasing nitric oxide concentration

    OpenAIRE

    Amirmansour, Charles; Vallance, Patrick; Bogle, Richard G

    1999-01-01

    Experiments were designed to explore the effects of nitric oxide (NO) donors on generation of superoxide (O2.−) and peroxynitrite (ONOO−) in rabbit aortic rings.Following inhibition of endogenous superoxide dismutase (SOD), significant basal release of O2.− was revealed (0.9±0.01×10−12 mol min−1 mg−1 tissue). Generation of O2.− increased in a concentration-dependent manner in response to NADH or NADPH (EC50=2.34±1.18×10−4 and 6.21±1.79×10−3 M respectively, n=4). NADH-stimulated O2.− chemilumi...

  14. Elementary students' engagement in failure-prone engineering design tasks

    Science.gov (United States)

    Andrews, Chelsea Joy

    Although engineering education has been practiced at the undergraduate level for over a century, only fairly recently has the field broadened to include the elementary level; the pre-college division of the American Society of Engineering Education was established in 2003. As a result, while recent education standards require engineering in elementary schools, current studies are still filling in basic research on how best to design and implement elementary engineering activities. One area in need of investigation is how students engage with physical failure in design tasks. In this dissertation, I explore how upper elementary students engage in failure-prone engineering design tasks in an out-of-school environment. In a series of three empirical case studies, I look closely at how students evaluate failed tests and decide on changes to their design constructions, how their reasoning evolves as they repeatedly encounter physical failure, and how students and facilitators co-construct testing norms where repetitive failure is manageable. I also briefly investigate how students' engagement differs in a task that features near-immediate success. By closely examining student groups' discourse and their interactions with their design constructions, I found that these students: are able to engage in iteration and see failure-as-feedback with minimal externally-imposed structure; seem to be designing in a more sophisticated manner, attending to multiple causal factors, after experiencing repetitive failure; and are able to manage the stress and frustration of repetitive failure, provided the co-constructed testing norms of the workshop environment are supportive of failure management. These results have both pedagogical implications, in terms of how to create and facilitate design tasks, and methodological implications--namely, I highlight the particular insights afforded by a case study approach for analyzing engagement in design tasks.

  15. Staying Engaged: Knowledge and Research Needs in Student Engagement

    Science.gov (United States)

    Wang, Ming-Te; Degol, Jessica

    2016-01-01

    In this article, we review knowledge about student engagement and look ahead to the future of study in this area. We begin by describing how researchers in the field define and study student engagement. In particular, we describe the levels, contexts, and dimensions that constitute the measurement of engagement, summarize the contexts that shape engagement and the outcomes that result from it, and articulate person-centered approaches for analyzing engagement. We conclude by addressing limitations to the research and providing recommendations for study. Specifically, we point to the importance of incorporating more work on how learning-related emotions, personality characteristics, prior learning experiences, shared values across contexts, and engagement in nonacademic activities influence individual differences in student engagement. We also stress the need to improve our understanding of the nuances involved in developing engagement over time by incorporating more extensive longitudinal analyses, intervention trials, research on affective neuroscience, and interactions among levels and dimensions of engagement. PMID:27087833

  16. Engagement and Skill Development in Biology Students through Analysis of Art

    Science.gov (United States)

    Milkova, Liliana; Crossman, Colette; Wiles, Stephanie; Allen, Taylor

    2013-01-01

    An activity involving analysis of art in biology courses was designed with the goals of piquing undergraduates’ curiosity, broadening the ways in which college students meaningfully engage with course content and concepts, and developing aspects of students’ higher-level thinking skills, such as analysis, synthesis, and evaluation. To meet these learning outcomes, the activity had three key components: preparatory readings, firsthand visual analysis of art during a visit to an art museum, and communication of the analysis. Following a presentation on the methodology of visual analysis, students worked in small groups to examine through the disciplinary lens of biology a selection of approximately 12 original artworks related in some manner to love. The groups then developed and presented for class members a mini-exhibition of several pieces addressing one of two questions: 1) whether portrayals of love in art align with the growing understanding of the biology of love or 2) whether the bodily experience of love is universal or, alternatively, is culturally influenced, as is the experience of depression. Evaluation of quantitative and qualitative assessment data revealed that the assignment engaged students, supported development of higher-level thinking skills, and prompted meaningful engagement with course material. PMID:24297295

  17. Engagement and skill development in biology students through analysis of art.

    Science.gov (United States)

    Milkova, Liliana; Crossman, Colette; Wiles, Stephanie; Allen, Taylor

    2013-01-01

    An activity involving analysis of art in biology courses was designed with the goals of piquing undergraduates' curiosity, broadening the ways in which college students meaningfully engage with course content and concepts, and developing aspects of students' higher-level thinking skills, such as analysis, synthesis, and evaluation. To meet these learning outcomes, the activity had three key components: preparatory readings, first-hand visual analysis of art during a visit to an art museum, and communication of the analysis. Following a presentation on the methodology of visual analysis, students worked in small groups to examine through the disciplinary lens of biology a selection of approximately 12 original artworks related in some manner to love. The groups then developed and presented for class members a mini-exhibition of several pieces addressing one of two questions: 1) whether portrayals of love in art align with the growing understanding of the biology of love or 2) whether the bodily experience of love is universal or, alternatively, is culturally influenced, as is the experience of depression. Evaluation of quantitative and qualitative assessment data revealed that the assignment engaged students, supported development of higher-level thinking skills, and prompted meaningful engagement with course material.

  18. Effects of maternal smoking and exposure to methylmercury on brain-derived neurotrophic factor concentrations in umbilical cord serum

    DEFF Research Database (Denmark)

    Spulber, Stefan; Rantamäki, Tomi; Nikkilä, Outi

    2010-01-01

    . The cohort consisted of 395 singleton births (206 boys and 189 girls), gestational age ranging from 38 to 42 weeks. Serum BDNF was measured by sandwich ELISA. Maternal smoking habits and other relevant factors were obtained by interviewing the mothers. The exposure to MeHg was estimated from Hg...... concentrations in cord blood, whereas exposure to PCB was estimated based on maternal serum concentrations. Only MeHg exposure affected the serum BDNF, which decreased in a concentration-dependent manner in girls born to nonsmoking mothers. Maternal smoking significantly increased BNDF in girls but not in boys....... For further statistical analyses, we used the serum BDNF concentration as a continuous outcome variable in supervised regression models. Serum BDNF concentration increased with gestational age, increased by maternal smoking, decreased slightly with MeHg exposure, and maternal smoking enhanced the decrease...

  19. Biological Effects of Osteoblast-Like Cells on Nanohydroxyapatite Particles at a Low Concentration Range

    Directory of Open Access Journals (Sweden)

    Xiaochen Liu

    2011-01-01

    Full Text Available The biological effects of osteoblast-like MG-63 cells on nanohydroxyapatite (n-HA at the low concentration range (5–25 g/mL for 5 days was investigated. The results showed the viability and actin cytoskeleton of the cells descended with the increase of the concentration of n-HA, and the actin cytoskeleton of cells was depolymerised and became more disordered. Apoptotic rate of cells (1.85%, 1.99%, and 2.29% increased with the increase of n-HA concentration (5, 15, and 25 g/mL and become significantly higher than the control. Total intracellular protein content decreased with n-HA concentration increase, showing significant difference between 25 g/mL and the control, and no significant change of ALP activity was observed at the 5th day. The results revealed that the cell growth was inhibited by n-HA in a concentration-dependent manner, and the obvious biological effects of MG-63 cells on n-HA existed at the low concentration range from 5 to 25 g/mL.

  20. Is a Transdisciplinary Theory of Engagement in Organized Settings Possible? A Concept Analysis of the Literature on Employee Engagement, Consumer Engagement and Patient Engagement.

    Science.gov (United States)

    Graffigna, Guendalina

    2017-01-01

    Organizations are experiencing increased competition, disruptive innovation, and continuous changes in their social and economic context. Furthermore, the decrease of resources (economic and human) in such a demanding context make it imperative for organizations to find new models and strategies to make their service delivery more sustainable at the economic, environmental and psychological levels. In such a complex scenario the concept of engagement of the individuals involved in organized settings (either as service providers or as final receivers) is a promising lever for innovation. However, despite the number of studies on the matter, the debate on engagement is still very fragmented because the corpus of literature addressing the different areas of engagement is divided and diverse in its nature. In this paper, we discuss the results of a conceptual analysis of the literature conducted in order to investigate overlapping features and areas of divergence among three different areas of investigation and application of the engagement phenomenon in organized settings: the domains of employee engagement, consumer engagement, and patient engagement. These are deliberately selected as prototypical of the phenomenon of engagement along the "inside/outside" of organizational settings. The analysis consisted in a qualitative conceptual survey? Of the scholarly literature indexed with the key terms "employee engagement," "consumer engagement," and "patient engagement." We performed a key-word based survey? Of the literature in the Scopus database. A total of 163 articles were selected and analyzed. The analysis cast light on the following areas of conceptual overlap among employee, consumer and patient engagement: (1) engagement is different from empowerment and activation; (2) engagement is a multi-componential psychological experience; (3) engagement is a self-transformative experience; (4) engagement develops within a relational context; (5) engagement is a systemic

  1. Is a Transdisciplinary Theory of Engagement in Organized Settings Possible? A Concept Analysis of the Literature on Employee Engagement, Consumer Engagement and Patient Engagement

    Directory of Open Access Journals (Sweden)

    Guendalina Graffigna

    2017-07-01

    Full Text Available Organizations are experiencing increased competition, disruptive innovation, and continuous changes in their social and economic context. Furthermore, the decrease of resources (economic and human in such a demanding context make it imperative for organizations to find new models and strategies to make their service delivery more sustainable at the economic, environmental and psychological levels. In such a complex scenario the concept of engagement of the individuals involved in organized settings (either as service providers or as final receivers is a promising lever for innovation. However, despite the number of studies on the matter, the debate on engagement is still very fragmented because the corpus of literature addressing the different areas of engagement is divided and diverse in its nature. In this paper, we discuss the results of a conceptual analysis of the literature conducted in order to investigate overlapping features and areas of divergence among three different areas of investigation and application of the engagement phenomenon in organized settings: the domains of employee engagement, consumer engagement, and patient engagement. These are deliberately selected as prototypical of the phenomenon of engagement along the “inside/outside” of organizational settings. The analysis consisted in a qualitative conceptual survey? Of the scholarly literature indexed with the key terms “employee engagement,” “consumer engagement,” and “patient engagement.” We performed a key-word based survey? Of the literature in the Scopus database. A total of 163 articles were selected and analyzed. The analysis cast light on the following areas of conceptual overlap among employee, consumer and patient engagement: (1 engagement is different from empowerment and activation; (2 engagement is a multi-componential psychological experience; (3 engagement is a self-transformative experience; (4 engagement develops within a relational context

  2. Strengthening stakeholder-engaged research and research on stakeholder engagement.

    Science.gov (United States)

    Ray, Kristin N; Miller, Elizabeth

    2017-06-01

    Stakeholder engagement is an emerging field with little evidence to inform best practices. Guidelines are needed to improve the quality of research on stakeholder engagement through more intentional planning, evaluation and reporting. We developed a preliminary framework for planning, evaluating and reporting stakeholder engagement, informed by published conceptual models and recommendations and then refined through our own stakeholder engagement experience. Our proposed exploratory framework highlights contexts and processes to be addressed in planning stakeholder engagement, and potential immediate, intermediate and long-term outcomes that warrant evaluation. We use this framework to illustrate both the minimum information needed for reporting stakeholder-engaged research and the comprehensive detail needed for reporting research on stakeholder engagement.

  3. Generational differences on work engagement levels of government healthcare institution employees

    Directory of Open Access Journals (Sweden)

    Veronica Hlongwane

    2015-04-01

    Full Text Available The objective of this study was to explore generational differences on work engagement levels of employees in a South African government healthcare institution. The Ultrech Work Engagement Scale measured the participants’ levels of work engagement and it was administered to a random sample size of government healthcare institution employees (n=289. Statistical analyses of the data were conducted and the results of ANOVA indicated that the levels of work engagement significantly differ depending on the employees’ generational cohort or group for the dimensions vigour, dedication and absorption. In terms of contributions and practical implications, recommendations are made regarding proposed organisational development interventions to enhance employees’ work engagement levels in a healthcare institution context as well as to conduct future research.

  4. Endothelium-Dependent Relaxation Effect of Apocynum venetum Leaf Extract via Src/PI3K/Akt Signalling Pathway

    Directory of Open Access Journals (Sweden)

    Yeh Siang Lau

    2015-06-01

    Full Text Available Botanical herbs are consumed globally not only as an essential diet but also as medicines or as functional/recreational food supplements. The extract of the Apocynum venetum leaves (AVLE, also known as Luobuma, exerts its antihypertensive effect via dilating the blood vessels in an endothelium- and concentration-dependent manner with optimal effect seen at as low as 10 µg/mL. A commercial Luoboma “antihypertensive tea” is available commercially in the western province of China. The present study seeks to investigate the underlying cellular mechanisms of the nitric oxide (NO-releasing property of AVLE in rat aortas and human umbilical vein endothelial cells (HUVECs. Endothelium-dependent relaxation induced by AVLE was assessed in organ chambers in the presence or absence of polyethyleneglycol catalase (PP2, 20 µM; inhibitor of Src kinase, wortmannin (30 nM and LY294002 (20 µM; PI3 (phosphatidylinositol3-Kinase inhibitor, NG-nitro-l-arginine (L-NAME, 100 µM; endothelial NO synthase inhibitor (eNOS and ODQ (1 µM; soluble guanylyl cyclase inhibitor. Total nitrite and nitrate (NOx level and protein expression of p-Akt and p-eNOS were measured. AVLE-induced endothelium-dependent relaxation was reduced by PP2, wortmannin and LY294002 and abolished by L-NAME and ODQ. AVLE significantly increased total NOx level in rat aortas and in HUVECs compared to control. It also instigated phosphorylation of Akt and eNOS in cultured HUVECs in a concentration-dependent manner and this was markedly suppressed by PP2, wortmannin and LY294002. AVLE also inhibited superoxide generated from both NADPH oxidase and xanthine/xanthine oxidase system. Taken together, AVLE causes endothelium-dependent NO mediated relaxations of rat aortas through Src/PI3K/Akt dependent NO signalling pathway and possesses superoxide scavenging activity.

  5. The H3K27 demethylase, Utx, regulates adipogenesis in a differentiation stage-dependent manner.

    Directory of Open Access Journals (Sweden)

    Kazushige Ota

    Full Text Available Understanding the molecular mechanisms that drive adipogenesis is important in developing new treatments for obesity and diabetes. Epigenetic regulations determine the capacity of adipogenesis. In this study, we examined the role of a histone H3 lysine 27 demethylase, the ubiquitously transcribed tetratricopeptide repeat protein on the X chromosome (Utx, in the differentiation of mouse embryonic stem cells (mESCs to adipocytes. Using gene trapping, we examined Utx-deficient male mESCs to determine whether loss of Utx would enhance or inhibit the differentiation of mESCs to adipocytes. Utx-deficient mESCs showed diminished potential to differentiate to adipocytes compared to that of controls. In contrast, Utx-deficient preadipocytes showed enhanced differentiation to adipocytes. Microarray analyses indicated that the β-catenin/c-Myc signaling pathway was differentially regulated in Utx-deficient cells during adipocyte differentiation. Therefore, our data suggest that Utx governs adipogenesis by regulating c-Myc in a differentiation stage-specific manner and that targeting the Utx signaling pathway could be beneficial for the treatment of obesity, diabetes, and congenital utx-deficiency disorders.

  6. Modeling the dependency of radon concentration levels inside ancient Egyptian tombs on the ambient temperature variations

    International Nuclear Information System (INIS)

    Metwally, S.M.; Abo-Elmagdb, M.; Salamaa, E.

    2007-01-01

    Radon concentration inside partially closed places like dwellings, caves and tombs, depends on many parameters. Some parameters are known quantitatively as radon exhalation rate for walls, decay constant, surface to volume ratio and outdoor concentration while other parameters as ventilation rate is in common known qualitatively due to useless of traditional methods (tracer gases) in many places as ancient Egyptian tombs. This work introduces a derived mathematical model to evaluate the sensitivity of radon concentration levels inside single sided opening places as ancient Egyptian tombs on the ambient temperature differences. The obtained formula for the natural ventilation rate depends on the indoor and outdoor temperature difference and the geometrical dimensions of the doorway. The effects of in and out flow mixing, air viscosity, streamline contraction, swirling flow and turbulence, were taken into consideration in terms of an empirical correction factor. According UNSCEAR reports, the exhalation rate Φ=C ra λ rn fρ s (1-ε)L; C ra the effective radium content, λ rn decay constant, f emanation fraction, ρ s soil grain density, ε porosity and L diffusion length, these are approximately static parameters but the variability of ambient temperature introduces a source of energy of fluctuating strength to radon atoms in rocks which controls the flow rate and the ambient content of radon. Therefore, the change of outdoor and indoor temperature difference causes fluctuation of value and direction of volume flow rate in such places consequently causes the daily variation and on average the seasonal variation of radon concentration. Therefore according to the present model, the daily accurate expectation of radon concentrations inside ancient Egyptian tombs, require precise measurements of indoor and outdoor temperatures

  7. Viewing time measures of sexual orientation in Samoan cisgender men who engage in sexual interactions with fa'afafine.

    Science.gov (United States)

    Petterson, Lanna J; Dixson, Barnaby J; Little, Anthony C; Vasey, Paul L

    2015-01-01

    Androphilia refers to attraction to adult males, whereas gynephilia refers to attraction to adult females. The current study employed self-report and viewing time (response time latency) measures of sexual attraction to determine the sexual orientation of Samoan cisgender men (i.e., males whose gender presentation and identity is concordant with their biological sex) who engage in sexual interactions with transgender male androphiles (known locally as fa'afafine) compared to: (1) Samoan cisgender men who only engage in sexual interactions with women, and (2) fa'afafine. As expected, both measures indicated that cisgender men who only engaged in sexual interactions with women exhibited a gynephilic pattern of sexual attraction, whereas fa'afafine exhibited an androphilic one. In contrast, both measures indicated that cisgender men who engaged in sexual interactions with fa'afafine demonstrated a bisexual pattern of sexual attraction. Most of the cisgender men who exhibited bisexual viewing times did not engage in sexual activity with both men and women indicating that the manner in which bisexual patterns of sexual attraction manifest behaviorally vary from one culture to the next.

  8. Viewing time measures of sexual orientation in Samoan cisgender men who engage in sexual interactions with fa'afafine.

    Directory of Open Access Journals (Sweden)

    Lanna J Petterson

    Full Text Available Androphilia refers to attraction to adult males, whereas gynephilia refers to attraction to adult females. The current study employed self-report and viewing time (response time latency measures of sexual attraction to determine the sexual orientation of Samoan cisgender men (i.e., males whose gender presentation and identity is concordant with their biological sex who engage in sexual interactions with transgender male androphiles (known locally as fa'afafine compared to: (1 Samoan cisgender men who only engage in sexual interactions with women, and (2 fa'afafine. As expected, both measures indicated that cisgender men who only engaged in sexual interactions with women exhibited a gynephilic pattern of sexual attraction, whereas fa'afafine exhibited an androphilic one. In contrast, both measures indicated that cisgender men who engaged in sexual interactions with fa'afafine demonstrated a bisexual pattern of sexual attraction. Most of the cisgender men who exhibited bisexual viewing times did not engage in sexual activity with both men and women indicating that the manner in which bisexual patterns of sexual attraction manifest behaviorally vary from one culture to the next.

  9. TIMP-1 mediates the inhibitory effect of interleukin-6 on the proliferation of a hepatocarcinoma cell line in a STAT3-dependent manner

    Directory of Open Access Journals (Sweden)

    S.-Y. Guo

    2007-05-01

    Full Text Available The tissue inhibitor of metalloproteinases (TIMP-1 is a multifunctional protein which is not only an inhibitor of matrix metalloproteinases (MMPs but also to have a possible "cytokine-like" action. Here, we first compared mRNA expression of TIMP-1 and MMP-9 in BEL-7402 (a hepatocellular carcinoma cell line, L-02 (a normal liver cell line and QSG-7701 (a cell line derived from peripheral tissue of liver carcinoma using real-time quantitative RT-PCR. By evaluating the variation of the MMP-9/TIMP-1 ratio as an index of reciprocal changes of the expression of the two genes, we observed that the MMP-9/TIMP-1 ratio was about 13- and 5-fold higher in BEL-7402 than in L-02 and QSG-7701, respectively. Significantly, overexpression of TIMP-1 decreased the MMP-9/TIMP-1 ratio in BEL-7402 and then inhibited the cell growth to 60% and reduced the migration to about 30%. Meanwhile, our data showed that interleukin-6 (IL-6 (100 ng/mL could also inhibited the cell growth of BEL-7402. Further studies indicated that TIMP-1 mediated the inhibitory effect of IL-6 on BEL-7402 cell proliferation in a STAT3-dependent manner, which could further accelerate the expression of the cyclin-dependent kinase inhibitor p21. A dominant negative STAT3 mutant totally abolished IL-6-induced TIMP-1 expression and its biological functions. The present results demonstrate that TIMP-1 may be one of the mediators that regulate the inhibitory effect of IL-6 on BEL-7402 proliferation in which STAT3 signal transduction and p21 up-regulation also play important roles.

  10. Growth hormone administration stimulates energy expenditure and extrathyroidal conversion of thyroxine to triiodothyronine in a dose-dependent manner and suppresses circadian thyrotrophin levels: studies in GH-deficient adults

    DEFF Research Database (Denmark)

    Laursen, Torben; Jørgensen, Jens Otto Lunde; Møller, Jens

    1994-01-01

    . CONCLUSIONS: GH administration stimulated peripheral T4 to T3 conversion in a dose-dependent manner. Serum T3 levels were subnormal despite T4 substitution when the patients were off GH but normalized with GH therapy. Energy expenditure increased with GH and correlated with free T3 levels. GH caused......Abstract OBJECTIVE: The impact of exogenous GH on thyroid function remains controversial although most data add support to a stimulation of peripheral T4 to T3 conversion. For further elucidation we evaluated iodothyronine and circadian TSH levels in GH-deficient patients as part of a GH dose...... without GH, whereas GH therapy significantly suppressed the TSH levels and blunted the circadian rhythm (mean TSH levels (mU/l) 0.546 +/- 0.246 (no GH) vs 0.066 +/- 0.031 (2 IU GH) (P

  11. The decision to engage cognitive control is driven by expected reward-value: neural and behavioral evidence.

    Directory of Open Access Journals (Sweden)

    Matthew L Dixon

    Full Text Available Cognitive control is a fundamental skill reflecting the active use of task-rules to guide behavior and suppress inappropriate automatic responses. Prior work has traditionally used paradigms in which subjects are told when to engage cognitive control. Thus, surprisingly little is known about the factors that influence individuals' initial decision of whether or not to act in a reflective, rule-based manner. To examine this, we took three classic cognitive control tasks (Stroop, Wisconsin Card Sorting Task, Go/No-Go task and created novel 'free-choice' versions in which human subjects were free to select an automatic, pre-potent action, or an action requiring rule-based cognitive control, and earned varying amounts of money based on their choices. Our findings demonstrated that subjects' decision to engage cognitive control was driven by an explicit representation of monetary rewards expected to be obtained from rule-use. Subjects rarely engaged cognitive control when the expected outcome was of equal or lesser value as compared to the value of the automatic response, but frequently engaged cognitive control when it was expected to yield a larger monetary outcome. Additionally, we exploited fMRI-adaptation to show that the lateral prefrontal cortex (LPFC represents associations between rules and expected reward outcomes. Together, these findings suggest that individuals are more likely to act in a reflective, rule-based manner when they expect that it will result in a desired outcome. Thus, choosing to exert cognitive control is not simply a matter of reason and willpower, but rather, conforms to standard mechanisms of value-based decision making. Finally, in contrast to current models of LPFC function, our results suggest that the LPFC plays a direct role in representing motivational incentives.

  12. Different Dose-Dependent Modes of Action of C-Type Natriuretic Peptide on Pseudomonas aeruginosa Biofilm Formation

    Directory of Open Access Journals (Sweden)

    Florie Desriac

    2018-04-01

    Full Text Available We have previously shown that the C-type Natriuretic Peptide (CNP, a peptide produced by lungs, is able to impact Pseudomonas aeruginosa physiology. In the present work, the effect of CNP at different concentrations on P. aeruginosa biofilm formation was studied and the mechanisms of action of this human hormone on P. aeruginosa were deciphered. CNP was shown to inhibit dynamic biofilm formation in a dose-dependent manner without affecting the bacterial growth at any tested concentrations. The most effective concentrations were 1 and 0.1 µM. At 0.1 µM, the biofilm formation inhibition was fully dependent on the CNP sensor protein AmiC, whereas it was only partially AmiC-dependent at 1 µM, revealing the existence of a second AmiC-independent mode of action of CNP on P. aeruginosa. At 1 µM, CNP reduced both P. aeruginosa adhesion on glass and di-rhamnolipid production and also increased the bacterial membrane fluidity. The various effects of CNP at 1 µM and 0.1 µM on P. aeruginosa shown here should have major consequences to design drugs for biofilm treatment or prevention.

  13. The Generating Mechanism of the Perlocutionary Effects of Train Manner Posters

    OpenAIRE

    水田, 洋子

    2013-01-01

    Manner posters, which are used for the purpose of improving people’s manners in public spaces, attempt to be effective without being impositional. How do they meet the challenge? Manner posters can be considered to perform speech acts with written words and visual devices. The current work investigates the generating mechanism of their perlocutionary effects such as persuasion. It provides a case study of Japanese train manner posters by Tokyo Metro in 2008-2010. The analysis is conducted wit...

  14. RAGBEEF: a FORTRAN IV implementation of a time-dependent model for radionuclide contamination of beef

    Energy Technology Data Exchange (ETDEWEB)

    Pleasant, J C; McDowell-Boyer, L M; Killough, G G

    1982-06-01

    RAGBEEF is a FORTRAN IV program that calculates radionuclide concentrations in beef as a result of ingestion of contaminated feeds, pasture, and pasture soil by beef cattle. The model implemented by RAGBEEF is dynamic in nature, allowing the user to consider age- and season-dependent aspects of beef cattle management in estimating concentrations in beef. It serves as an auxiliary code to RAGTIME, previously documented by the authors, which calculates radionuclide concentrations in agricultural crops in a dynamic manner, but evaluates concentrations in beef for steady-state conditions only. The time-dependent concentrations in feeds, pasture, and pasture soil generated by RAGTIME are used as input to the RAGBEEF code. RAGBEEF, as presently implemented, calculates radionuclide concentrations in the muscle of age-based cohorts in a beef cattle herd. Concentrations in the milk of lactating cows are also calculated, but are assumed age-dependent as in RAGTIME. Radionuclide concentrations in beef and milk are described in RAGBEEF by a system of ordinary linear differential equations in which the transfer rate of radioactivity between compartments is proportional to the inventory of radioactivity in the source compartment. This system is solved by use of the GEAR package for solution of systems of ordinary differential equations. The accuracy of this solution is monitored at various check points by comparison with explicit solutions of Bateman-type equations. This report describes the age- and season-dependent considerations making up the RAGBEEF model, as well as presenting the equations which describe the model and a documentation of the associated computer code. Listings of the RAGBEEF and updated RAGTIME codes are provided in appendices, as are the results of a sample run of RAGBEEF and a description of recent modifications to RAGTIME.

  15. RAGBEEF: a FORTRAN IV implementation of a time-dependent model for radionuclide contamination of beef

    International Nuclear Information System (INIS)

    Pleasant, J.C.; McDowell-Boyer, L.M; Killough, G.G.

    1982-06-01

    RAGBEEF is a FORTRAN IV program that calculates radionuclide concentrations in beef as a result of ingestion of contaminated feeds, pasture, and pasture soil by beef cattle. The model implemented by RAGBEEF is dynamic in nature, allowing the user to consider age- and season-dependent aspects of beef cattle management in estimating concentrations in beef. It serves as an auxiliary code to RAGTIME, previously documented by the authors, which calculates radionuclide concentrations in agricultural crops in a dynamic manner, but evaluates concentrations in beef for steady-state conditions only. The time-dependent concentrations in feeds, pasture, and pasture soil generated by RAGTIME are used as input to the RAGBEEF code. RAGBEEF, as presently implemented, calculates radionuclide concentrations in the muscle of age-based cohorts in a beef cattle herd. Concentrations in the milk of lactating cows are also calculated, but are assumed age-dependent as in RAGTIME. Radionuclide concentrations in beef and milk are described in RAGBEEF by a system of ordinary linear differential equations in which the transfer rate of radioactivity between compartments is proportional to the inventory of radioactivity in the source compartment. This system is solved by use of the GEAR package for solution of systems of ordinary differential equations. The accuracy of this solution is monitored at various check points by comparison with explicit solutions of Bateman-type equations. This report describes the age- and season-dependent considerations making up the RAGBEEF model, as well as presenting the equations which describe the model and a documentation of the associated computer code. Listings of the RAGBEEF and updated RAGTIME codes are provided in appendices, as are the results of a sample run of RAGBEEF and a description of recent modifications to RAGTIME

  16. The effect of a concentration-dependent viscosity on particle transport in a channel flow with porous walls

    KAUST Repository

    Herterich, James G.; Griffiths, Ian M.; Vella, Dominic; Field, Robert W.

    2014-01-01

    The transport of a dilute suspension of particles through a channel with porous walls, accounting for the concentration dependence of the viscosity, is analyzed. In particular, we study two cases of fluid permeation through the porous channel walls

  17. The Engagement of Employees as a Key to Corporate Success

    Directory of Open Access Journals (Sweden)

    Ole Bloch Jensen

    2012-11-01

    Full Text Available One of the major barriers to achieving a higher level of corporate success is the lack of employee engagement. The main goal of this article is to propose the process of engaging all employees and thus setting the scene for the future of their organisation. In the author's opinion, the only resource that most organizations do not fully utilize is the engagement and full potential of their employees. The author explains the signs of disengagement and discusses its causes. They are mainly in the area of soft processes of management, in leadership, motivation and communication. It is the author's belief that the engagement of employees strongly depends on their managers, above all their managers' soft skills. The process of how to build and develop the interest and involvement of employees is described in detail. Furthermore, the importance of manager-employees relationships for engagement is emphasized.

  18. Oxidative stress and antioxidant responses to increasing concentrations of trivalent chromium in the Andean crop species Chenopodium quinoa Willd.

    Science.gov (United States)

    Scoccianti, Valeria; Bucchini, Anahi E; Iacobucci, Marta; Ruiz, Karina B; Biondi, Stefania

    2016-11-01

    Quinoa (Chenopodium quinoa Willd), an ancient Andean seed crop, exhibits exceptional nutritional properties and resistance to abiotic stress. The species' tolerance to heavy metals has, however, not yet been investigated nor its ability to take up and translocate chromium (Cr). This study aimed to investigate the metabolic adjustments occurring upon exposure of quinoa to several concentrations (0.01-5mM) of CrCl3. Young hydroponically grown plants were used to evaluate Cr uptake, growth, oxidative stress, and other biochemical parameters three and/or seven days after treatment. Leaves accumulated the lowest amounts of Cr, while roots and stems accumulated the most at low and at high metal concentrations, respectively. Fresh weight and photosynthetic pigments were reduced only by the higher Cr(III) doses. Substantially increased lipid peroxidation, hydrogen peroxide, and proline levels were observed only with 5mM Cr(III). Except for a significant decrease at day 7 with 5mM Cr(III), total polyphenols and flavonoids maintained control levels in Cr(III)-treated plants, whereas antioxidant activity increased in a dose-dependent manner. Maximum polyamine accumulation was observed in 1mM CrCl3-treated plants. Even though α- and γ-tocopherols also showed enhanced levels only with the 1mM concentration, tyrosine aminotransferase (TAT, EC 2.6.1.5) activity increased under Cr(III) treatment in a dose- and time-dependent manner. Taken together, results suggest that polyamines, tocopherols, and TAT activity could contribute to tolerance to 1mM Cr(III), but not to the highest concentration that, instead, generated oxidative stress. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Engagement as a Driver of Growth of Online Health Forums: Observational Study.

    Science.gov (United States)

    Gopalsamy, Rahul; Semenov, Alexander; Pasiliao, Eduardo; McIntosh, Scott; Nikolaev, Alexander

    2017-08-29

    The emerging research on nurturing the growth of online communities posits that it is in part attributed to network effects, wherein every increase in the volume of user-generated content increases the value of the community in the eyes of its potential new members. The recently introduced metric engagement capacity offers a means of quantitatively assessing the ability of online platform users to engage each other into generating content; meanwhile, the quantity engagement value is useful for quantifying communication-based platform use. If the claim that higher engagement leads to accelerated growth holds true for online health forums (OHFs), then engagement tracking should become an important tool in the arsenal of OHF managers. Indeed, it might allow for quantifying the ability of an OHF to exploit network effects, thus predicting the OHF's future success. This study aimed to empirically analyze the relationship between internal OHF use (quantified using engagement measurement), and external growth. We collected data from 7 OHFs posted between the years 1999 and 2016. Longitudinal analyses were conducted by evaluating engagement in the OHFs over time. We analyzed 2-way causality effects between the engagement value and metrics evaluating OHF growth using Granger causality tests. User activity metrics per week were correlated with engagement metrics, followed by linear regression analyses. Observational data showed a 1-way causal relationship between the OHF engagement value and reach (P=.02). We detected a 2-way causal relationship between the engagement value and delurking, with further analysis indicating that the engagement value was more likely to cause delurking (PUsers who engaged each other more were more likely (up to 14 times, depending on how much one user engaged another) to develop personal connections. Finally, we found that the more engaging an OHF user was in a given week, the more likely (up to 2 times, depending on their ability to engage

  20. 26 CFR 1.9005-4 - Manner of exercising election.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Manner of exercising election. 1.9005-4 Section 1.9005-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES General Actuarial Valuations § 1.9005-4 Manner of exercising election. (a...

  1. 26 CFR 1.9004-4 - Manner of exercising election.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Manner of exercising election. 1.9004-4 Section 1.9004-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES General Actuarial Valuations § 1.9004-4 Manner of exercising election. (a...

  2. 26 CFR 1.9002-8 - Manner of exercising elections.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Manner of exercising elections. 1.9002-8 Section 1.9002-8 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES General Actuarial Valuations § 1.9002-8 Manner of exercising elections...

  3. 26 CFR 1.9003-4 - Manner of exercising election.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Manner of exercising election. 1.9003-4 Section 1.9003-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES General Actuarial Valuations § 1.9003-4 Manner of exercising election. (a...

  4. Dependence of plant biometrics of cutting lettuce (Lactuca sativa L. varietis on the concentration of microfertilizer Avatar-1

    Directory of Open Access Journals (Sweden)

    В. Б. Кутовенко

    2017-09-01

    Full Text Available Purpose. To investigate the variability of plant biometrics of cutting lettuce (Lactuca sativa L. varieties depending on the concentration of microfertilizer Avatar-1. Methods. Field study, biometric technique, comparative approach, statistical evaluation, generalization. Results. Dependence of the plant height, the diameter of the leaf rosette, the number of leaves per plant, the leaf area of plants on the concentration of microfertilizer Avatar-1 was defined. Investigations of cutting lettuce ‘Afitsyon’ and ‘Concord’ varieties by Dutch breeding were conducted in 2016–2017 in the collection sites of the department of vegetable growing in the scientific-experimental field  “Fruit and vegetable garden” of the National University of Life and Environmental Sciences of Ukraine. In order to determine dependence of plant biometrics of cutting lettuce varieties on the concentration of complex microfertilizer Avatar-1, the following scheme was used for the both varieties: variant 1 – water (control; variant 2 – 0,10% solution; variant 3 – 0,25% solution; variant 4 – 0,50% solution. Plants were treated with microfertilizer three times during the vegetative period. Alterations of plant biometrics of cutting lettuce ‘Afitsyon’ and ‘Concord’ varieties  depending on the concentration of complex microfertilizer Avatar-1 was studied. Conclusions. It was found that in case of three-time plant treatment with complex microfertilizer Avatar-1 at the time of harvesting, the best plant biometrics was registered in variant 3 (concentration 0,25% for the both ‘Afitsyon’ and ‘Concord’ varie­ties of cutting lettuce. The height of plants of the cutting lettuce in ‘Afitsyon’ variety exceeded this figure in ‘Concord variety by 1,1–1,4 cm. The concentration of microfertilizer had no significant effect on the diameter of the leaf rosette of ‘Concord’ variety (25,1–25,9 см. The diame­ter of the leaf rosette of

  5. Global regulator SATB1 recruits beta-catenin and regulates T(H2 differentiation in Wnt-dependent manner.

    Directory of Open Access Journals (Sweden)

    Dimple Notani

    2010-01-01

    Full Text Available In vertebrates, the conserved Wnt signalling cascade promotes the stabilization and nuclear accumulation of beta-catenin, which then associates with the lymphoid enhancer factor/T cell factor proteins (LEF/TCFs to activate target genes. Wnt/beta -catenin signalling is essential for T cell development and differentiation. Here we show that special AT-rich binding protein 1 (SATB1, the T lineage-enriched chromatin organizer and global regulator, interacts with beta-catenin and recruits it to SATB1's genomic binding sites. Gene expression profiling revealed that the genes repressed by SATB1 are upregulated upon Wnt signalling. Competition between SATB1 and TCF affects the transcription of TCF-regulated genes upon beta-catenin signalling. GATA-3 is a T helper type 2 (T(H2 specific transcription factor that regulates production of T(H2 cytokines and functions as T(H2 lineage determinant. SATB1 positively regulated GATA-3 and siRNA-mediated knockdown of SATB1 downregulated GATA-3 expression in differentiating human CD4(+ T cells, suggesting that SATB1 influences T(H2 lineage commitment by reprogramming gene expression. In the presence of Dickkopf 1 (Dkk1, an inhibitor of Wnt signalling, GATA-3 is downregulated and the expression of signature T(H2 cytokines such as IL-4, IL-10, and IL-13 is reduced, indicating that Wnt signalling is essential for T(H2 differentiation. Knockdown of beta-catenin also produced similar results, confirming the role of Wnt/beta-catenin signalling in T(H2 differentiation. Furthermore, chromatin immunoprecipitation analysis revealed that SATB1 recruits beta-catenin and p300 acetyltransferase on GATA-3 promoter in differentiating T(H2 cells in a Wnt-dependent manner. SATB1 coordinates T(H2 lineage commitment by reprogramming gene expression. The SATB1:beta-catenin complex activates a number of SATB1 regulated genes, and hence this study has potential to find novel Wnt responsive genes. These results demonstrate that SATB1

  6. Caffeine potentiates or protects against radiation-induced DNA and chromosomal damage in human lymphocytes depending on temperature and concentration

    International Nuclear Information System (INIS)

    Stoilov, L.M.; Mullenders, L.H.F.; Natarajan, A.T.

    1994-01-01

    The effect of caffeine on radiation-induced chromosomal aberrations and DNA strand breaks in unstimulated human lymphocytes was investigated. When present prior to and during the radiation exposure, caffeine treatment was found to cause either potentiation or protection against induction of chromosomal aberrations depending on the concentration and temperature. When the nucleoid sedimentation technique was applied, enhancement or reduction of radiation-induced DNA strand breaks by caffeine was also found to be dependent on temperature and caffeine concentration. It is proposed that caffeine, in addition to its suspected ability to influence DNA repair, can also influence the induction of DNA damage, leading to alterations in the yield of chromosomal aberrations

  7. Caffeine potentiates or protects against radiation-induced DNA and chromosomal damage in human lymphocytes depending on temperature and concentration

    Energy Technology Data Exchange (ETDEWEB)

    Stoilov, L.M. (Department of Molecular Genetics, Institute of Genetics, Sofia (Bulgaria)); Mullenders, L.H.F.; Natarajan, A.T. (J.A. Cohen Institute, Interuniversity Research Institute for Radiopathology and Radiation Protection, Leiden (Netherlands))

    1994-12-01

    The effect of caffeine on radiation-induced chromosomal aberrations and DNA strand breaks in unstimulated human lymphocytes was investigated. When present prior to and during the radiation exposure, caffeine treatment was found to cause either potentiation or protection against induction of chromosomal aberrations depending on the concentration and temperature. When the nucleoid sedimentation technique was applied, enhancement or reduction of radiation-induced DNA strand breaks by caffeine was also found to be dependent on temperature and caffeine concentration. It is proposed that caffeine, in addition to its suspected ability to influence DNA repair, can also influence the induction of DNA damage, leading to alterations in the yield of chromosomal aberrations.

  8. Mechanisms Involved in Guiding the Preference for Fat Emulsion Differ Depending on the Concentration.

    Science.gov (United States)

    Sakamoto, Kazuhiro; Matsumura, Shigenobu; Okafuji, Yoko; Eguchi, Ai; Lee, Shinhye; Adachi, Shin-ichi; Fujitani, Mina; Tsuzuki, Satoshi; Inoue, Kazuo; Fushiki, Tohru

    2015-01-01

    High-fat foods tend to be palatable and can cause addiction in mice via a reinforcing effect. However, mice showed preference for low fat concentrations that do not elicit a reinforcing effect in a two-bottle choice test with water as the alternative. This behavior indicates the possibility that the mechanism underlying fat palatability may differ depending on the dietary fat content. To address this issue, we examined the influences of the opioid system and olfactory and gustatory transductions on the intake and reinforcing effects of various concentrations of a dietary fat emulsion (Intralipid). We found that the intake and reinforcing effects of fat emulsion were reduced by the administration of an opioid receptor antagonist (naltrexone). Furthermore, the action of naltrexone was only observed at higher concentrations of fat emulsion. The intake and the reinforcing effects of fat emulsion were also reduced by olfactory and glossopharyngeal nerve transections (designated ONX and GLX, respectively). In contrast to naltrexone, the effects of ONX and GLX were mainly observed at lower concentrations of fat emulsion. These results imply that the opioid system seems to have a greater role in determining the palatability of high-fat foods unlike the contribution of olfactory and glossopharyngeal nerves.

  9. 26 CFR 1.853-4 - Manner of making election.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 9 2010-04-01 2010-04-01 false Manner of making election. 1.853-4 Section 1.853-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Regulated Investment Companies and Real Estate Investment Trusts § 1.853-4 Manner of...

  10. Modeling the dependency of radon concentration levels inside ancient Egyptian tombs on the ambient temperature variations

    Energy Technology Data Exchange (ETDEWEB)

    Metwally, S M; Abo-Elmagdb, M [Faculty of Science, Department of Physics, Ain Shams University, P. O. Box 11566, Cairo (Egypt); Salamaa, E [National Institute for Standard, Radiation Measurements Department, Cairo (Egypt)

    2007-06-15

    Radon concentration inside partially closed places like dwellings, caves and tombs, depends on many parameters. Some parameters are known quantitatively as radon exhalation rate for walls, decay constant, surface to volume ratio and outdoor concentration while other parameters as ventilation rate is in common known qualitatively due to useless of traditional methods (tracer gases) in many places as ancient Egyptian tombs. This work introduces a derived mathematical model to evaluate the sensitivity of radon concentration levels inside single sided opening places as ancient Egyptian tombs on the ambient temperature differences. The obtained formula for the natural ventilation rate depends on the indoor and outdoor temperature difference and the geometrical dimensions of the doorway. The effects of in and out flow mixing, air viscosity, streamline contraction, swirling flow and turbulence, were taken into consideration in terms of an empirical correction factor. According UNSCEAR reports, the exhalation rate {phi}=C{sub ra}{lambda}{sub rn} f{rho}{sub s}(1-{epsilon})L; C{sub ra} the effective radium content, {lambda}{sub rn} decay constant, f emanation fraction, {rho}{sub s} soil grain density, {epsilon} porosity and L diffusion length, these are approximately static parameters but the variability of ambient temperature introduces a source of energy of fluctuating strength to radon atoms in rocks which controls the flow rate and the ambient content of radon. Therefore, the change of outdoor and indoor temperature difference causes fluctuation of value and direction of volume flow rate in such places consequently causes the daily variation and on average the seasonal variation of radon concentration. Therefore according to the present model, the daily accurate expectation of radon concentrations inside ancient Egyptian tombs, require precise measurements of indoor and outdoor temperatures.

  11. Induced terpene accumulation in Norway spruce inhibits bark beetle colonization in a dose-dependent manner.

    Directory of Open Access Journals (Sweden)

    Tao Zhao

    Full Text Available Tree-killing bark beetles (Coleoptera, Scolytinae are among the most economically and ecologically important forest pests in the northern hemisphere. Induction of terpenoid-based oleoresin has long been considered important in conifer defense against bark beetles, but it has been difficult to demonstrate a direct correlation between terpene levels and resistance to bark beetle colonization.To test for inhibitory effects of induced terpenes on colonization by the spruce bark beetle Ips typographus (L. we inoculated 20 mature Norway spruce Picea abies (L. Karsten trees with a virulent fungus associated with the beetle, Ceratocystis polonica (Siem. C. Moreau, and investigated induced terpene levels and beetle colonization in the bark.Fungal inoculation induced very strong and highly variable terpene accumulation 35 days after inoculation. Trees with high induced terpene levels (n = 7 had only 4.9% as many beetle attacks (5.1 vs. 103.5 attacks m(-2 and 2.6% as much gallery length (0.029 m m(-2 vs. 1.11 m m(-2 as trees with low terpene levels (n = 6. There was a highly significant rank correlation between terpene levels at day 35 and beetle colonization in individual trees. The relationship between induced terpene levels and beetle colonization was not linear but thresholded: above a low threshold concentration of ∼100 mg terpene g(-1 dry phloem trees suffered only moderate beetle colonization, and above a high threshold of ∼200 mg terpene g(-1 dry phloem trees were virtually unattacked.This is the first study demonstrating a dose-dependent relationship between induced terpenes and tree resistance to bark beetle colonization under field conditions, indicating that terpene induction may be instrumental in tree resistance. This knowledge could be useful for developing management strategies that decrease the impact of tree-killing bark beetles.

  12. Career Engagement: Bridging Career Counseling and Employee Engagement

    Science.gov (United States)

    Neault, Roberta A.; Pickerell, Deirdre A.

    2011-01-01

    In this article, the authors present a model of career engagement that helps bridge the gap between career counselors' focus on supporting individuals to find meaningful work and employers' desire for an engaged, productive, and committed workforce. They briefly review highlights of the employee engagement literature, introduce the Career…

  13. Relationship Model of Personality, Communication, Student Engagement, and Learning Satisfaction

    Directory of Open Access Journals (Sweden)

    Dorothea Ariani

    2015-12-01

    Full Text Available This study aims to examine the engagement as a mediating variable of the relationship between personality and communication with satisfaction. This study was conducted at business school in Indonesia with 307 students who are still active as a respondent. Survey research was conducted over four months by questionnaire that has been well-established that was taken and modified from previous studies. The results of this study indicate that student engagement mediates the relationship between personality and communication as independent variables and satisfaction as the dependent variable. Extroversion personality and communication significantly positive effect on student engagement in all three dimensions (vigor, dedication, and absorption. In addition, this study also showed that engagement and satisfaction are two different variables, but correlated, and there was no difference in terms of gender differences involvement.

  14. Global Think Tank Initiative Policy Engagement and ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Think tanks in developing countries aim to produce quality, evidence-based research to address the policy challenges faced by the countries or regions within which they operate. The potential for think tanks to inform policy and contribute to development debates depends on their ability to engage in the policy process.

  15. Building professionalism and employability skills: embedding employer engagement within first-year computing modules

    Science.gov (United States)

    Hanna, Philip; Allen, Angela; Kane, Russell; Anderson, Neil; McGowan, Aidan; Collins, Matthew; Hutchison, Malcolm

    2015-07-01

    This paper outlines a means of improving the employability skills of first-year university students through a closely integrated model of employer engagement within computer science modules. The outlined approach illustrates how employability skills, including communication, teamwork and time management skills, can be contextualised in a manner that directly relates to student learning but can still be linked forward into employment. The paper tests the premise that developing employability skills early within the curriculum will result in improved student engagement and learning within later modules. The paper concludes that embedding employer participation within first-year models can help relate a distant notion of employability into something of more immediate relevance in terms of how students can best approach learning. Further, by enhancing employability skills early within the curriculum, it becomes possible to improve academic attainment within later modules.

  16. Anomalous spreading of a density front from an infinite continuous source in a concentration-dependent lattice gas automaton diffusion model

    CERN Document Server

    Kuentz, M

    2003-01-01

    A two-dimensional lattice gas automaton (LGA) is used for simulating concentration-dependent diffusion in a microscopically random heterogeneous structure. The heterogeneous medium is initialized at a low density rho sub 0 and then submitted to a steep concentration gradient by continuous injection of particles at a concentration rho sub 1 >rho sub 0 from a one-dimensional source to model spreading of a density front. Whereas the nonlinear diffusion equation generally used to describe concentration-dependent diffusion processes predicts a scaling law of the type phi = xt sup - sup 1 sup / sup 2 in one dimension, the spreading process is shown to deviate from the expected t sup 1 sup / sup 2 scaling. The time exponent is found to be larger than 1/2, i.e. diffusion of the density front is enhanced with respect to standard Fickian diffusion. It is also established that the anomalous time exponent decreases as time elapses: anomalous spreading is thus not a timescaling process. We demonstrate that occurrence of a...

  17. Hypoxia Downregulates MAPK/ERK but Not STAT3 Signaling in ROS-Dependent and HIF-1-Independent Manners in Mouse Embryonic Stem Cells

    Directory of Open Access Journals (Sweden)

    Jan Kučera

    2017-01-01

    Full Text Available Hypoxia is involved in the regulation of stem cell fate, and hypoxia-inducible factor 1 (HIF-1 is the master regulator of hypoxic response. Here, we focus on the effect of hypoxia on intracellular signaling pathways responsible for mouse embryonic stem (ES cell maintenance. We employed wild-type and HIF-1α-deficient ES cells to investigate hypoxic response in the ERK, Akt, and STAT3 pathways. Cultivation in 1% O2 for 24 h resulted in the strong dephosphorylation of ERK and its upstream kinases and to a lesser extent of Akt in an HIF-1-independent manner, while STAT3 phosphorylation remained unaffected. Downregulation of ERK could not be mimicked either by pharmacologically induced hypoxia or by the overexpression. Dual-specificity phosphatases (DUSP 1, 5, and 6 are hypoxia-sensitive MAPK-specific phosphatases involved in ERK downregulation, and protein phosphatase 2A (PP2A regulates both ERK and Akt. However, combining multiple approaches, we revealed the limited significance of DUSPs and PP2A in the hypoxia-mediated attenuation of ERK signaling. Interestingly, we observed a decreased reactive oxygen species (ROS level in hypoxia and a similar phosphorylation pattern for ERK when the cells were supplemented with glutathione. Therefore, we suggest a potential role for the ROS-dependent attenuation of ERK signaling in hypoxia, without the involvement of HIF-1.

  18. Bullatacin Triggered ABCB1-Overexpressing Cell Apoptosis via the Mitochondrial-Dependent Pathway

    Directory of Open Access Journals (Sweden)

    Yong-Ju Liang

    2009-01-01

    Full Text Available This paper was to explore bullatacin-mediated multidrug-resistant cell apoptosis at extremely low concentration. To investigate its precise mechanisms, the pathway of cell apoptosis induced by bullatacin was examined. Bullatacin causes an upregulation of ROS and a downregulation of ΔΨm in a concentration-dependent manner in ABCB1-overexpressing KBv200 cells. In addition, cleavers of caspase-9, caspase-3, and PARP were observed following the release of cytochrome c from mitochondria after bullatacin treatment. However, neither cleavage of caspase-8 nor change of expression level of bcl-2, bax and Fas was observed by the same treatment. Pretreating KBv200 cells with N-acetylcysteine, an antioxidant modulator, resulted in a significant reduction of ROS generation and cell apoptosis induced by bullatacin. Bullatacin-induced apoptosis was antagonized by z-LEHD-fmk, a caspase-9 inhibitor, but not by z-IETD-fmk, a caspase-8 inhibitor. These implied that apoptosis of KBv200 cells induced by bullatacin was associated with the mitochondria-dependent pathway that was limited to activation of apical caspase-9.

  19. Saponarin activates AMPK in a calcium-dependent manner and suppresses gluconeogenesis and increases glucose uptake via phosphorylation of CRTC2 and HDAC5.

    Science.gov (United States)

    Seo, Woo-Duck; Lee, Ji Hae; Jia, Yaoyao; Wu, Chunyan; Lee, Sung-Joon

    2015-11-15

    This study investigated the molecular mechanism of saponarin, a flavone glucoside, in the regulation of insulin sensitivity. Saponarin suppressed the rate of gluconeogenesis and increased cellular glucose uptake in HepG2 and TE671 cells by regulating AMPK. Using an in vitro kinase assay, we showed that saponarin did not directly interact with the AMPK protein. Instead, saponarin increased intracellular calcium levels and induced AMPK phosphorylation, which was diminished by co-stimulation with STO-609, an inhibitor of CAMKKβ. Transcription of hepatic gluconeogenesis genes was upregulated by nuclear translocation of CRTC2 and HDAC5, coactivators of CREB and FoxO1 transcription factors, respectively. This nuclear translocation was inhibited by increased phosphorylation of CRTC2 and HDAC5 by saponarin-induced AMPK in HepG2 cells and suppression of CREB and FoxO1 transactivation activities in cells stimulated by saponarin. The results from a chromatin immunoprecipitation assay confirmed the reduced binding of CRTC2 on the PEPCK and G6Pase promoters. In TE671 cells, AMPK phosphorylated HDAC5, which suppressed nuclear penetration and upregulated GLUT4 transcription, leading to enhanced glucose uptake. Collectively, these results suggest that saponarin activates AMPK in a calcium-dependent manner, thus regulating gluconeogenesis and glucose uptake. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Collaborative engagement experiment (CEE)

    Science.gov (United States)

    Wade, Robert L.; Reames, Joseph M.

    2005-05-01

    Unmanned ground and air systems operating in collaboration have the potential to provide future Joint Forces a significant capability for operations in complex terrain. Ground and air collaborative engagements potentially offer force conservation, perform timely acquisition and dissemination of essential combat information, and can eliminate high value and time critical targets. These engagements can also add considerably to force survivability by reducing soldier and equipment exposure during critical operations. The Office of the Secretary of Defense, Joint Robotics Program (JRP) sponsored Collaborative Engagement Experiment (CEE) is a consolidation of separate Air Force, Army and Navy collaborative efforts to provide a Joint capability. The Air Force Research Laboratory (AFRL), Material and Manufacturing Directorate, Aerospace Expeditionary Force Division, Force Protection Branch (AFRLMLQF), The Army Aviation and Missile Research, Development and Engineering Center (AMRDEC) Joint Technology Center (JTC)/Systems Integration Laboratory (SIL), and the Space and Naval Warfare Systems Center-San Diego (SSC San Diego) are conducting technical research and proof of principle for an envisioned operational concept for extended range, three dimensional, collaborative operations between unmanned systems, with enhanced situational awareness for lethal operations in complex terrain. This program will assess information requirements and conduct experiments to identify and resolve technical risks for collaborative engagements using Unmanned Ground Vehicles (UGVs) and Unmanned Aerial Vehicles (UAVs). It will research, develop and physically integrate multiple unmanned systems and conduct live collaborative experiments. Modeling and Simulation systems will be upgraded to reflect engineering fidelity levels to greater understand technical challenges to operate as a team. This paper will provide an update of a multi-year program and will concentrate primarily on the JTC

  1. Concentration-Dependent Protection by Ethanol Extract of Propolis against γ-Ray-Induced Chromosome Damage in Human Blood Lymphocytes

    Directory of Open Access Journals (Sweden)

    A. Montoro

    2011-01-01

    Full Text Available Radioprotection with natural products may be relevant to the mitigation of ionizing radiation-induced damage in mammalian systems; in this sense, propolis extracts have shown effects such as antioxidant, antitumoral, anti-inflammatory, and immunostimulant. We report for the first time a cytogenetic study to evaluate the radioprotective effect, in vitro, of propolis against radiation-induced chromosomal damage. Lymphocytes were cultured with increasing concentrations of ethanol extract of propolis (EEP, including 20, 40, 120, 250, 500, 750, 1000, and 2000 μg mL−1 and then exposed to 2 Gy γ-rays. A significant and concentration-dependent decrease is observed in the frequency of chromosome aberrations in samples treated with EEP. The protection against the formation of dicentrics was concentration-dependent, with a maximum protection at 120 μg mL−1 of EEP. The observed frequency of dicentrics is described as negative exponential function, indicating that the maximum protectible fraction of dicentrics is approximately 44%. Free radical scavenging and antioxidant activities are the mechanisms that these substances use to protect cells from ionizing radiation.

  2. Time-dependent irisin concentration changes in patients affected by overt hypothyroidism.

    Science.gov (United States)

    Zybek-Kocik, Ariadna; Sawicka-Gutaj, Nadia; Wrotkowska, Elżbieta; Sowiński, Jerzy; Ruchała, Marek

    2016-01-01

    Irisin, a cleaved and secreted part of the transmembrane protein FNDC5, is a recently discovered adipo-myokine that is said to have a significant influence on body metabolism. Changes in thyrometabolic state may also alter the serum irisin level. Since already reported data are not fully consistent, the aim of the present research is to evaluate the time-dependent changes in serum irisin level in patients affected by overt hypothyroidism. The study involved 36 subjects - two groups of 12 patients with long-lasting (AITD) and short-term (TC) overt hypothyroidism, and a control group (CG) of 12 subjects, matched for age and gender. Serum irisin level, thyrometabolic state, creatine kinase (CK - muscle damage marker), glucose, and insulin concentration were assessed and compared between groups. The irisin level was significantly lower in AITD than in TC and CG (p = 0.02; p 0.05). There was no significant difference between free triiodothyronine and free thyroxine levels in AITD and TC patients (p > 0.05). CK concentration was significantly higher in AITD than in CG patients (p 0.05) as well as TC and CG patients (p > 0.05). Additionally, the CK level negatively correlated with the irisin level (r = -0.58; p hypothyroidism have lower irisin levels that those with short-term disorder. (Endokrynol Pol 2016; 67 (5): 476-480).

  3. Concentration-dependent sedimentation properties of ferritin: implications for estimation of iron contents of serum ferritins

    International Nuclear Information System (INIS)

    Niitsu, Y.; Adachi, C.; Takahashi, F.; Goto, Y.; Kohgo, Y.; Urushizaki, I.; Listowsky, I.

    1985-01-01

    Serum ferritins from various sources sedimented at lower densities than tissue ferritins in sucrose gradient centrifugation systems. The sedimentation patterns of ferritins, however, were shown to be dependent on the concentration of the protein; as the concentration decreased the protein appeared to sediment at lower densities. Thus, at the low concentration levels usually used for analysis of serum ferritin, tissue ferritins also sedimented in the same lower density regions. Iron labeling experiments indicated that the sedimentation changes upon dilution were not due to release of iron or was there any indication that the protein dissociated into subunits. The anomalous sedimentation behavior of serum ferritin should therefore not be interpreted in terms of its iron content. The disclosure that serum ferritins may have full complements of iron is counter to the prevalent view that serum ferritins are low iron forms and has potential implications with regard to the sources and possible function of this protein in the circulation

  4. Concentration dependence of solute atoms on vacancy cluster formation in neutron irradiated Ni alloy

    International Nuclear Information System (INIS)

    Sato, K.; Itoh, D.; Yoshiie, T.; Xu, Q.

    2007-01-01

    Full text of publication follows: One dimensional (1-D) motion of interstitial clusters is important for the microstructural evolution in metals. The movement of interstitial clusters was often observed in neutron irradiated metals by transmission electron microscopy (TEM). Alloying elements are expected to affect the motion of interstitial clusters. Yoshiie et al. have studied the effect of alloying elements in Ni. For example, in neutron irradiated pure Ni, well-developed dislocation networks and voids were observed at 573 K at a dose of 0.026 dpa by TEM. After the addition of 2at.%Si (-5.81% volume size factor to Ni) and Sn (74.08% volume size factor), no voids were detected by TEM observation and positron lifetime measurement. Alloying elements of Si and Sn were expected to prevent the 1-D motion of the interstitial clusters. In this study, the concentration dependence of alloying elements on the 1-D motion of the interstitial clusters was investigated by positron annihilation lifetime measurements, and the microstructural evolution was discussed. Specimens irradiated were 99.99 pure Ni (Johnson Matthey) and Ni based binary alloys, which contain Si, Cu, Ge and Sn as solute atoms. The concentration of solute atoms was 0.05at.%o, 0.3at.% and 2at.%. Neutron irradiation was performed with the Kyoto University Reactor (KUR) and Japan materials testing reactor (JMTR) at Japan Atomic Energy Agency. Neutron dose was 6x10 -5 -1x10 -2 dpa at KUR, and 8x10 -3 -0.3 dpa at JMTR. Irradiation temperature was 573 K at KUR and 563 K at JMTR. After the neutron irradiation, positron annihilation lifetime measurements were performed at room temperature. Microvoids were detected in pure Ni, Ni-0.05%Si, Ni-0.05%Sn, Ni-Cu and Ni-Ge alloys. In Ni-Si and Ni-Sn alloys, the size of microvoids decreased as the concentration of solute atoms increased. This is because the frequency of 1-D motion of the interstitial clusters depends on the alloy concentration. High concentration of alloying

  5. Concentration dependence of solute atoms on vacancy cluster formation in neutron irradiated Ni alloy

    Energy Technology Data Exchange (ETDEWEB)

    Sato, K.; Itoh, D.; Yoshiie, T.; Xu, Q. [Kyoto Univ., Research Reactor Institute, Osaka (Japan)

    2007-07-01

    Full text of publication follows: One dimensional (1-D) motion of interstitial clusters is important for the microstructural evolution in metals. The movement of interstitial clusters was often observed in neutron irradiated metals by transmission electron microscopy (TEM). Alloying elements are expected to affect the motion of interstitial clusters. Yoshiie et al. have studied the effect of alloying elements in Ni. For example, in neutron irradiated pure Ni, well-developed dislocation networks and voids were observed at 573 K at a dose of 0.026 dpa by TEM. After the addition of 2at.%Si (-5.81% volume size factor to Ni) and Sn (74.08% volume size factor), no voids were detected by TEM observation and positron lifetime measurement. Alloying elements of Si and Sn were expected to prevent the 1-D motion of the interstitial clusters. In this study, the concentration dependence of alloying elements on the 1-D motion of the interstitial clusters was investigated by positron annihilation lifetime measurements, and the microstructural evolution was discussed. Specimens irradiated were 99.99 pure Ni (Johnson Matthey) and Ni based binary alloys, which contain Si, Cu, Ge and Sn as solute atoms. The concentration of solute atoms was 0.05at.%o, 0.3at.% and 2at.%. Neutron irradiation was performed with the Kyoto University Reactor (KUR) and Japan materials testing reactor (JMTR) at Japan Atomic Energy Agency. Neutron dose was 6x10{sup -5}-1x10{sup -2} dpa at KUR, and 8x10{sup -3} -0.3 dpa at JMTR. Irradiation temperature was 573 K at KUR and 563 K at JMTR. After the neutron irradiation, positron annihilation lifetime measurements were performed at room temperature. Microvoids were detected in pure Ni, Ni-0.05%Si, Ni-0.05%Sn, Ni-Cu and Ni-Ge alloys. In Ni-Si and Ni-Sn alloys, the size of microvoids decreased as the concentration of solute atoms increased. This is because the frequency of 1-D motion of the interstitial clusters depends on the alloy concentration. High

  6. Genomic Analysis Reveals Distinct Concentration-Dependent Evolutionary Trajectories for Antibiotic Resistance in Escherichia coli

    Science.gov (United States)

    Mogre, Aalap; Sengupta, Titas; Veetil, Reshma T.; Ravi, Preethi; Seshasayee, Aswin Sai Narain

    2014-01-01

    Evolution of bacteria under sublethal concentrations of antibiotics represents a trade-off between growth and resistance to the antibiotic. To understand this trade-off, we performed in vitro evolution of laboratory Escherichia coli under sublethal concentrations of the aminoglycoside kanamycin over short time durations. We report that fixation of less costly kanamycin-resistant mutants occurred earlier in populations growing at lower sublethal concentration of the antibiotic, compared with those growing at higher sublethal concentrations; in the latter, resistant mutants with a significant growth defect persisted longer. Using deep sequencing, we identified kanamycin resistance-conferring mutations, which were costly or not in terms of growth in the absence of the antibiotic. Multiple mutations in the C-terminal end of domain IV of the translation elongation factor EF-G provided low-cost resistance to kanamycin. Despite targeting the same or adjacent residues of the protein, these mutants differed from each other in the levels of resistance they provided. Analysis of one of these mutations showed that it has little defect in growth or in synthesis of green fluorescent protein (GFP) from an inducible plasmid in the absence of the antibiotic. A second class of mutations, recovered only during evolution in higher sublethal concentrations of the antibiotic, deleted the C-terminal end of the ATP synthase shaft. This mutation confers basal-level resistance to kanamycin while showing a strong growth defect in the absence of the antibiotic. In conclusion, the early dynamics of the development of resistance to an aminoglycoside antibiotic is dependent on the levels of stress (concentration) imposed by the antibiotic, with the evolution of less costly variants only a matter of time. PMID:25281544

  7. The relationship between transformational leadership and work engagement in governmental hospitals nurses: a survey study.

    Science.gov (United States)

    Hayati, Davood; Charkhabi, Morteza; Naami, Abdolzahra

    2014-01-14

    The aim of this study was to determine the effects of transformational leadership and its components on work engagement among hospital nurses. There are a few set of researches that have focused on the effects of transformational leadership on work engagement in nurses. A descriptive, correlational, cross-sectional design was used. In this study, 240 nurses have been chosen by stratified random sampling method which filled related self-reported scales include multifactor leadership questionnaire (MLQ) and work engagement scale. Data analysis has been exerted according to the statistical method of simple and multiple correlation coefficients. Findings indicated that the effect of this type of leadership on work engagement and its facets is positive and significant. In addition, the research illustrates that transformational leaders transfer their enthusiasm and high power to their subordinates by the way of modeling. This manner can increase the power as a component of work engagement in workers. Idealized influence among these leaders can result in forming a specific belief among employees toward those leaders and leaders can easily transmit their inspirational motivation to them. Consequently, it leads to make a positive vision by which, and by setting high standards, challenges the employees and establishes zeal along with optimism for attaining success in works. regarding to the results we will expand leadership and work engagement literature in hospital nurses. Also, we conclude with theoretical and practical implications and propose a clear horizon for future researches.

  8. Dependence of electrical resistance in nonstoichiometric titanium carbide TiCy on carbon vacancy concentration and distribution

    International Nuclear Information System (INIS)

    Lipatnikov, V.N.; Gusev, A.I.

    1999-01-01

    Electric conductivity in nonstoichiometric titanium carbide TiC y (0.5 ≤ y ≤ 0.98) is studied depending on concentration and distribution of carbon sublattice vacancies as well as on temperature. It is established that in TiC y at y y on the one hand and by the atom-vacancy interaction on the other hand [ru

  9. 29 CFR 1614.703 - Manner and format of data.

    Science.gov (United States)

    2010-07-01

    ... § 1614.704(a) through (m). (3) When posting data pursuant to § 1614.704(d) and (j), bases of... 29 Labor 4 2010-07-01 2010-07-01 false Manner and format of data. 1614.703 Section 1614.703 Labor... Retaliation Act of 2002 (No FEAR Act) § 1614.703 Manner and format of data. (a) Agencies shall post their...

  10. A Novel Reconfigurable Logic Unit Based on the DNA-Templated Potassium-Concentration-Dependent Supramolecular Assembly.

    Science.gov (United States)

    Yang, Chunrong; Zou, Dan; Chen, Jianchi; Zhang, Linyan; Miao, Jiarong; Huang, Dan; Du, Yuanyuan; Yang, Shu; Yang, Qianfan; Tang, Yalin

    2018-03-15

    Plenty of molecular circuits with specific functions have been developed; however, logic units with reconfigurability, which could simplify the circuits and speed up the information process, are rarely reported. In this work, we designed a novel reconfigurable logic unit based on a DNA-templated, potassium-concentration-dependent, supramolecular assembly, which could respond to the input stimuli of H + and K + . By inputting different concentrations of K + , the logic unit could implement three significant functions, including a half adder, a half subtractor, and a 2-to-4 decoder. Considering its reconfigurable ability and good performance, the novel prototypes developed here may serve as a promising proof of principle in molecular computers. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. The Development of a Program Engagement Theory for Group Offending Behavior Programs.

    Science.gov (United States)

    Holdsworth, Emma; Bowen, Erica; Brown, Sarah; Howat, Douglas

    2017-10-01

    Offender engagement in group offending behavior programs is poorly understood and under-theorized. In addition, there is no research on facilitators' engagement. This article presents the first ever theory to address this gap. A Program Engagement Theory (PET) was derived from a constructivist grounded theory analysis that accounts for both facilitators' and offenders' engagement in group offending behavior programs (GOBPs). Interviews and session observations were used to collect data from 23 program facilitators and 28 offenders (group members). The analysis revealed that group members' engagement involved shared identities and moving on as a group. In turn, this was dependent on facilitators personalising treatment frameworks and establishing a hook to help group members move on. The PET emphasizes the importance of considering change during treatment as a process rather than simply a program outcome. Solution-focused (SF) programs were more conducive to engagement and the change process than offence-focused programs.

  12. Electron-induced desorption of europium atoms from oxidized tungsten surface: concentration dependence of low-energy peak

    CERN Document Server

    Davydov, S Y

    2002-01-01

    One discusses nature of electron induced desorption of Eu sup 0 europium atoms under E sub e irradiating electron low-energies (approx 30 eV) and peculiarities of yield dependence of Eu sup 0 atoms on their concentration at oxidized tungsten surface. Primary act of vacancy origination in europium adatom inner 5p-shell turned to be the determining stage. Evaluations have shown that just the first of two possible scenarios of ionization (electron intra-atomic to Eu adatom external quasi-level or realise of knocked out electron into vacuum) leads to Eu sup 0 desorption. One determined concentration threshold for yield of Eu sup 0 atoms

  13. Doxycycline-loaded nanotube-modified adhesives inhibit MMP in a dose-dependent fashion.

    Science.gov (United States)

    Palasuk, Jadesada; Windsor, L Jack; Platt, Jeffrey A; Lvov, Yuri; Geraldeli, Saulo; Bottino, Marco C

    2018-04-01

    This article evaluated the drug loading, release kinetics, and matrix metalloproteinase (MMP) inhibition of doxycycline (DOX) released from DOX-loaded nanotube-modified adhesives. DOX was chosen as the model drug, since it is the only MMP inhibitor approved by the U.S. Food and Drug Administration. Drug loading into the nanotubes was accomplished using DOX solution at distinct concentrations. Increased concentrations of DOX significantly improved the amount of loaded DOX. The modified adhesives were fabricated by incorporating DOX-loaded nanotubes into the adhesive resin of a commercial product. The degree of conversion (DC), Knoop microhardness, DOX release kinetics, antimicrobial, cytocompatibility, and anti-MMP activity of the modified adhesives were investigated. Incorporation of DOX-loaded nanotubes did not compromise DC, Knoop microhardness, or cell compatibility. Higher concentrations of DOX led to an increase in DOX release in a concentration-dependent manner from the modified adhesives. DOX released from the modified adhesives did not inhibit the growth of caries-related bacteria, but more importantly, it did inhibit MMP-1 activity. The loading of DOX into the nanotube-modified adhesives did not compromise the physicochemical properties of the adhesives and the released levels of DOX were able to inhibit MMP activity without cytotoxicity. Doxycycline released from the nanotube-modified adhesives inhibited MMP activity in a concentration-dependent fashion. Therefore, the proposed nanotube-modified adhesive may hold clinical potential as a strategy to preserve resin/dentin bond stability.

  14. Concentration-dependent behaviors of bone marrow derived mesenchymal stem cells and infectious bacteria toward magnesium oxide nanoparticles.

    Science.gov (United States)

    Wetteland, Cheyann Lee; Nguyen, Nhu-Y Thi; Liu, Huinan

    2016-04-15

    This article reports the quantitative relationship between the concentration of magnesium oxide (MgO) nanoparticles and its distinct biological activities towards mammalian cells and infectious bacteria for the first time. The effects of MgO nanoparticles on the viability of bone marrow derived mesenchymal stem cells (BMSCs) and infectious bacteria (both gram-negative Escherichia coli and gram-positive Staphylococcus epidermidis) showed a concentration-dependent behavior in vitro. The critical concentrations of MgO nanoparticles identified in this study provided valuable guidelines for biomaterial design toward potential clinical translation. BMSCs density increased significantly when cultured in 200μg/mL of MgO in comparison to the Cells Only control without MgO. The density of BMSCs decreased significantly after culture in the media with 500μg/mL or more of MgO. Concentrations at or above 1000μg/mL of MgO resulted in complete BMSCs death. Quantification of colony forming units (CFU) revealed that the minimum bactericidal concentration (MBC) of MgO for E. coli and S. epidermidis was 1200μg/mL. The addition of MgO nanoparticles into the cultures increased the pH and Mg(2+) ion concentration in the respective culture media, which might have played a role in the observed cell responses but not the main factors. E. coli and S. epidermidis still proliferated significantly at alkaline pH up to 10 or with supplemental Mg(2+) dosages up to 50mM, indicating bactericidal properties of MgO are beyond the effects of increased media pH and Mg(2+) ion concentrations. MgO nanoparticles at a concentration of 200μg/mL provided dual benefits of promoting BMSC proliferation while reducing bacterial adhesion, which should be further studied for potential medical implant applications. The use of free MgO nanoparticles yielded detrimental effects to BMSCs in concentrations above 300μg/mL. We recommend further study into MgO nanoparticle as a coating material or as a part of a

  15. Intracellular invasion of Orientia tsutsugamushi activates inflammasome in asc-dependent manner.

    Directory of Open Access Journals (Sweden)

    Jung-Eun Koo

    Full Text Available Orientia tsutsugamushi, a causative agent of scrub typhus, is an obligate intracellular bacterium, which escapes from the endo/phagosome and replicates in the host cytoplasm. O. tsutsugamushi infection induces production of pro-inflammatory mediators including interleukin-1β (IL-1β, which is secreted mainly from macrophages upon cytosolic stimuli by activating cysteine protease caspase-1 within a complex called the inflammasome, and is a key player in initiating and maintaining the inflammatory response. However, the mechanism for IL-1β maturation upon O. tsutsugamushi infection has not been identified. In this study, we show that IL-1 receptor signaling is required for efficient host protection from O. tsutsugamushi infection. Live Orientia, but not heat- or UV-inactivated Orientia, activates the inflammasome through active bacterial uptake and endo/phagosomal maturation. Furthermore, Orientia-stimulated secretion of IL-1β and activation of caspase-1 are ASC- and caspase-1- dependent since IL-1β production was impaired in Asc- and caspase-1-deficient macrophages but not in Nlrp3-, Nlrc4- and Aim2-deficient macrophages. Therefore, live O. tsutsugamushi triggers ASC inflammasome activation leading to IL-1β production, which is a critical innate immune response for effective host defense.

  16. Temperature and concentration dependences of the electrical resistivity for alloys of plutonium with americium under normal conditions

    Science.gov (United States)

    Tsiovkin, Yu. Yu.; Povzner, A. A.; Tsiovkina, L. Yu.; Dremov, V. V.; Kabirova, L. R.; Dyachenko, A. A.; Bystrushkin, V. B.; Ryabukhina, M. V.; Lukoyanov, A. V.; Shorikov, A. O.

    2010-01-01

    The temperature and concentration dependences of the electrical resistivity for alloys of americium with plutonium are analyzed in terms of the multiband conductivity model for binary disordered substitution-type alloys. For the case of high temperatures ( T > ΘD, ΘD is the Debye temperature), a system of self-consistent equations of the coherent potential approximation has been derived for the scattering of conduction electrons by impurities and phonons without any constraints on the interaction intensity. The definitions of the shift and broadening operator for a single-electron level are used to show qualitatively and quantitatively that the pattern of the temperature dependence of the electrical resistivity for alloys is determined by the balance between the coherent and incoherent contributions to the electron-phonon scattering and that the interference conduction electron scattering mechanism can be the main cause of the negative temperature coefficient of resistivity observed in some alloys involving actinides. It is shown that the great values of the observed resistivity may be attributable to interband transitions of charge carriers and renormalization of their effective mass through strong s-d band hybridization. The concentration and temperature dependences of the resistivity for alloys of plutonium and americium calculated in terms of the derived conductivity model are compared with the available experimental data.

  17. Dimensions of self-concept and sports engagement in early adolescence

    Directory of Open Access Journals (Sweden)

    Tubić Tatjana

    2012-01-01

    Full Text Available The aim of this paper is to examine the differences in particular dimensions of selfconcept in female and male adolescents depending on sports engagement, as well as to determine which domain-specific self-perceptions provide the highest contributions to global self-worth in female and male adolescents engaged in sport and those not engaged in it. This research included 400 subjects at early adolescent age, of both genders (235 females and 164 males further divided to sub-samples of athletes and non-athletes. An adapted version of a scale Self-Perception Profile for Adolescents (Harter, 1988 was applied, which consists of nine subscales. The obtained results indicate that sport-engaged adolescents of both genders provide more favourable perception of themselves in most tested aspects of self-concept than those not engaged in an organized sports activity. Engagement in sport has special effect on selfconcept of male adolescents. Results of multiple regression analysis point out unambiguously the significance of self-perception of physical appearance in global self-worth of adolescents of both genders, irrespective of whether they are involved in sports activity or not.

  18. In a World That Counts: Clustering and Detecting Fake Social Engagement at Scale

    OpenAIRE

    Li, Yixuan; Martinez, Oscar; Chen, Xing; Li, Yi; Hopcroft, John

    2015-01-01

    How can web services that depend on user generated content discern fake social engagement activities by spammers from legitimate ones? In this paper, we focus on the social site of YouTube and the problem of identifying bad actors posting inorganic contents and inflating the count of social engagement metrics. We propose an effective method, Leas (Local Expansion at Scale), and show how the fake engagement activities on YouTube can be tracked over time by analyzing the temporal graph based on...

  19. Engaged to Learn Ways of Engaging ESL Learners

    Directory of Open Access Journals (Sweden)

    Brian Tomlinson

    2010-01-01

    Full Text Available In this paper I am going to argue that our most important role as language teachers is to provide potentially engaging materials for our learners and then to make use of them in optimally engaging ways. If we do not engage our learners most of the time no amount of exposure, teaching, practice or use of the language will help them to achieve sufficient language acquisition and development.

  20. Alignment method for parabolic trough solar concentrators

    Science.gov (United States)

    Diver, Richard B [Albuquerque, NM

    2010-02-23

    A Theoretical Overlay Photographic (TOP) alignment method uses the overlay of a theoretical projected image of a perfectly aligned concentrator on a photographic image of the concentrator to align the mirror facets of a parabolic trough solar concentrator. The alignment method is practical and straightforward, and inherently aligns the mirror facets to the receiver. When integrated with clinometer measurements for which gravity and mechanical drag effects have been accounted for and which are made in a manner and location consistent with the alignment method, all of the mirrors on a common drive can be aligned and optimized for any concentrator orientation.

  1. Serious engagement in sport and health benefits among Korean immigrants in the USA

    Directory of Open Access Journals (Sweden)

    Junhyoung Kim

    2016-08-01

    Full Text Available There is a dearth of information pertaining to ethnicity and serious leisure among immigrants. The purpose of our study was to explore the health benefits of serious engagement in sports among Korean immigrants who are part of club activities. Using semi-structured in-depth interviews, we identified three themes associated with the benefits of serious leisure: (a coping with acculturative stress, (b creating ethnic strength, and (c personal benefits. Participants gain personal and social benefits by pursuing leisure activities in a serious manner within their ethnic in-group.

  2. Serious engagement in sport and health benefits among Korean immigrants in the USA.

    Science.gov (United States)

    Kim, Junhyoung; Kim, May; Henderson, Karla A; Han, Areum; Park, Se-Hyuk

    2016-01-01

    There is a dearth of information pertaining to ethnicity and serious leisure among immigrants. The purpose of our study was to explore the health benefits of serious engagement in sports among Korean immigrants who are part of club activities. Using semi-structured in-depth interviews, we identified three themes associated with the benefits of serious leisure: (a) coping with acculturative stress, (b) creating ethnic strength, and (c) personal benefits. Participants gain personal and social benefits by pursuing leisure activities in a serious manner within their ethnic in-group.

  3. Glycoprotein 90K Promotes E-Cadherin Degradation in a Cell Density-Dependent Manner via Dissociation of E-Cadherin–p120-Catenin Complex

    Directory of Open Access Journals (Sweden)

    So-Yeon Park

    2017-12-01

    Full Text Available Glycoprotein 90K (also known as LGALS3BP or Mac-2BP is a tumor-associated protein, and high 90K levels are associated with poor prognosis in some cancers. To clarify the role of 90K as an indicator for poor prognosis and metastasis in epithelial cancers, the present study investigated the effect of 90K on an adherens junctional protein, E-cadherin, which is frequently absent or downregulated in human epithelial cancers. Treatment of certain cancer cells with 90K significantly reduced E-cadherin levels in a cell-population-dependent manner, and these cells showed decreases in cell adhesion and increases in invasive cell motility. Mechanistically, 90K-induced E-cadherin downregulation occurred via ubiquitination-mediated proteasomal degradation. 90K interacted with the E-cadherin–p120-catenin complex and induced its dissociation, altering the phosphorylation status of p120-catenin, whereas it did not associate with β-catenin. In subconfluent cells, 90K decreased membrane-localized p120-catenin and the membrane fraction of the p120-catenin. Particularly, 90K-induced E-cadherin downregulation was diminished in p120-catenin knocked-down cells. Taken together, 90K upregulation promotes the dissociation of the E-cadherin–p120-catenin complex, leading to E-cadherin proteasomal degradation, and thereby destabilizing adherens junctions in less confluent tumor cells. Our results provide a potential mechanism to explain the poor prognosis of cancer patients with high serum 90K levels.

  4. Multipotent Adult Progenitor Cells Suppress T Cell Activation in In Vivo Models of Homeostatic Proliferation in a Prostaglandin E2-Dependent Manner

    Science.gov (United States)

    Carty, Fiona; Corbett, Jennifer M.; Cunha, João Paulo M. C. M.; Reading, James L.; Tree, Timothy I. M.; Ting, Anthony E.; Stubblefield, Samantha R.; English, Karen

    2018-01-01

    Lymphodepletion strategies are used in the setting of transplantation (including bone marrow, hematopoietic cell, and solid organ) to create space or to prevent allograft rejection and graft versus host disease. Following lymphodepletion, there is an excess of IL-7 available, and T cells that escape depletion respond to this cytokine undergoing accelerated proliferation. Moreover, this environment promotes the skew of T cells to a Th1 pro-inflammatory phenotype. Existing immunosuppressive regimens fail to control this homeostatic proliferative (HP) response, and thus the development of strategies to successfully control HP while sparing T cell reconstitution (providing a functioning immune system) represents a significant unmet need in patients requiring lymphodepletion. Multipotent adult progenitor cells (MAPC®) have the capacity to control T cell proliferation and Th1 cytokine production. Herein, this study shows that MAPC cells suppressed anti-thymocyte globulin-induced cytokine production but spared T cell reconstitution in a pre-clinical model of lymphodepletion. Importantly, MAPC cells administered intraperitoneally were efficacious in suppressing interferon-γ production and in promoting the expansion of regulatory T cells in the lymph nodes. MAPC cells administered intraperitoneally accumulated in the omentum but were not present in the spleen suggesting a role for soluble factors. MAPC cells suppressed lymphopenia-induced cytokine production in a prostaglandin E2-dependent manner. This study suggests that MAPC cell therapy may be useful as a novel strategy to target lymphopenia-induced pathogenic T cell responses in lymphodepleted patients. PMID:29740426

  5. The dependence of magnetic ordering temperature in amorphous semiconductors on paramagnetic centre concentration

    International Nuclear Information System (INIS)

    Khokhlov, A.F.; Mashin, A.I.; Satanin, A.M.

    1981-01-01

    In silicon amorphized by ion implantation (a-Si) the dependence of magnetic ordering temperature (theta) on localized spin concentration (Nsub(s)) is studied by EPR method. Nsub(s) changes by varying the Ne + ion dose from 6x10 14 to 2x10 17 cm -2 and sample annealing. From the comparison of the data obtained with literature ones conclusions are made about the existence of two critical values of Nsub(s) in a-Si (approximately 10 19 and approximately 2x10 20 cm -3 ), when a transition occurs from paramagnetism to antiferromagnetism (at T < theta) and from antiferromagnetism to ferromagnetism, respectively. (author)

  6. Both RIG-I and MDA5 detect alphavirus replication in concentration-dependent mode

    Energy Technology Data Exchange (ETDEWEB)

    Akhrymuk, Ivan; Frolov, Ilya; Frolova, Elena I., E-mail: evfrolova@UAB.edu

    2016-01-15

    Alphaviruses are a family of positive-strand RNA viruses that circulate on all continents between mosquito vectors and vertebrate hosts. Despite a significant public health threat, their biology is not sufficiently investigated, and the mechanisms of alphavirus replication and virus–host interaction are insufficiently understood. In this study, we have applied a variety of experimental systems to further understand the mechanism by which infected cells detect replicating alphaviruses. Our new data strongly suggest that activation of the antiviral response by alphavirus-infected cells is determined by the integrity of viral genes encoding proteins with nuclear functions, and by the presence of two cellular pattern recognition receptors (PRRs), RIG-I and MDA5. No type I IFN response is induced in their absence. The presence of either of these PRRs is sufficient for detecting virus replication. However, type I IFN activation in response to pathogenic alphaviruses depends on the basal levels of RIG-I or MDA5. - Highlights: • Both RIG-I and MDA5 detect alphavirus replication. • Alphavirus-induced transcriptional shutoff affects type I IFN induction. • Sensing of alphavirus replication by RIG-I and MDA5 depends on their concentrations. • High basal level of RIG-I and MDA5 allows IFN induction by pathogenic alphaviruses. • This dependence determines the discrepancy between the in vivo and in vitro data.

  7. Cell density dependence of Microcystis aeruginosa responses to copper algaecide concentrations: Implications for microcystin-LR release.

    Science.gov (United States)

    Kinley, Ciera M; Iwinski, Kyla J; Hendrikse, Maas; Geer, Tyler D; Rodgers, John H

    2017-11-01

    Along with mechanistic models, predictions of exposure-response relationships for copper are often derived from laboratory toxicity experiments with standardized experimental exposures and conditions. For predictions of copper toxicity to algae, cell density is a critical factor often overlooked. For pulse exposures of copper-based algaecides in aquatic systems, cell density can significantly influence copper sorbed by the algal population, and consequent responses. A cyanobacterium, Microcystis aeruginosa, was exposed to a copper-based algaecide over a range of cell densities to model the density-dependence of exposures, and effects on microcystin-LR (MC-LR) release. Copper exposure concentrations were arrayed to result in a gradient of MC-LR release, and masses of copper sorbed to algal populations were measured following exposures. While copper exposure concentrations eliciting comparable MC-LR release ranged an order of magnitude (24-h EC50s 0.03-0.3mg Cu/L) among cell densities of 10 6 through 10 7 cells/mL, copper doses (mg Cu/mg algae) were similar (24-h EC50s 0.005-0.006mg Cu/mg algae). Comparisons of MC-LR release as a function of copper exposure concentrations and doses provided a metric of the density dependence of algal responses in the context of copper-based algaecide applications. Combined with estimates of other site-specific factors (e.g. water characteristics) and fate processes (e.g. dilution and dispersion, sorption to organic matter and sediments), measuring exposure-response relationships for specific cell densities can refine predictions for in situ exposures and algal responses. These measurements can in turn decrease the likelihood of amending unnecessary copper concentrations to aquatic systems, and minimize risks for non-target aquatic organisms. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. DASH-FP, Multicomponent Time-Dependent Concentration Diffusion

    International Nuclear Information System (INIS)

    Apperson, C.E. Jr.; Carruthers, L.M.; Shinn, J.F.; Lee, C.E.

    1995-01-01

    1 - Description of program or function: The program DASH-FP calculates the transient concentration of multiple diffusing species with radioactive decay. 2 - Method of solution: Uses finite difference and exponential operator techniques

  9. SAP modulates B cell functions in a genetic background-dependent manner.

    Science.gov (United States)

    Detre, Cynthia; Yigit, Burcu; Keszei, Marton; Castro, Wilson; Magelky, Erica M; Terhorst, Cox

    2013-06-01

    Mutations affecting the SLAM-associated protein (SAP) are responsible for the X-linked lympho-proliferative syndrome (XLP), a severe primary immunodeficiency syndrome with disease manifestations that include fatal mononucleosis, B cell lymphoma and dysgammaglobulinemia. It is well accepted that insufficient help by SAP-/- CD4+ T cells, in particular during the germinal center reaction, is a component of dysgammaglobulinemia in XLP patients and SAP-/- animals. It is however not well understood whether in XLP patients and SAP-/- mice B cell functions are affected, even though B cells themselves do not express SAP. Here we report that B cell intrinsic responses to haptenated protein antigens are impaired in SAP-/- mice and in Rag-/- mice into which B cells derived from SAP-/- mice together with wt CD4+ T cells had been transferred. This impaired B cells functions are in part depending on the genetic background of the SAP-/- mouse, which affects B cell homeostasis. Surprisingly, stimulation with an agonistic anti-CD40 causes strong in vivo and in vitro B cell responses in SAP-/- mice. Taken together, the data demonstrate that genetic factors play an important role in the SAP-related B cell functions. The finding that anti-CD40 can in part restore impaired B cell responses in SAP-/- mice, suggests potentially novel therapeutic interventions in subsets of XLP patients. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Temperature dependence of 1H NMR chemical shifts and its influence on estimated metabolite concentrations.

    Science.gov (United States)

    Wermter, Felizitas C; Mitschke, Nico; Bock, Christian; Dreher, Wolfgang

    2017-12-01

    Temperature dependent chemical shifts of important brain metabolites measured by localised 1 H MRS were investigated to test how the use of incorrect prior knowledge on chemical shifts impairs the quantification of metabolite concentrations. Phantom measurements on solutions containing 11 metabolites were performed on a 7 T scanner between 1 and 43 °C. The temperature dependence of the chemical shift differences was fitted by a linear model. Spectra were simulated for different temperatures and analysed by the AQSES program (jMRUI 5.2) using model functions with chemical shift values for 37 °C. Large differences in the temperature dependence of the chemical shift differences were determined with a maximum slope of about ±7.5 × 10 -4  ppm/K. For 32-40 °C, only minor quantification errors resulted from using incorrect chemical shifts, with the exception of Cr and PCr. For 1-10 °C considerable quantification errors occurred if the temperature dependence of the chemical shifts was neglected. If 1 H MRS measurements are not performed at 37 °C, for which the published chemical shift values have been determined, the temperature dependence of chemical shifts should be considered to avoid systematic quantification errors, particularly for measurements on animal models at lower temperatures.

  11. Tumour exosomes display different differential mechanical and complement activation properties dependent on malignant state: implications in endothelial leakiness

    DEFF Research Database (Denmark)

    Whitehead, Bradley Joseph; Wu, Linping; Hvam, Michael Lykke

    2015-01-01

    (QNM AFM) to determine size and nanomechanical properties. Effect of HCV-29, T24 and FL3 exosomes on human umbilical vein endothelial cell (HUVEC) monolayer integrity was determined by transendothelial electrical resistance (TEER) measurements and transport was determined by flow cytometry. Complement......). Malignant cell-derived exosomes activated complement through calcium-sensitive pathways in a concentration-dependent manner. Conclusions : Malignant (metastatic and non-metastatic) cell line exosomes display a markedly reduced stiffness and adhesion but an increased complement activation compared to non...

  12. Death Receptor-Induced Apoptosis Signalling Regulation by Ezrin Is Cell Type Dependent and Occurs in a DISC-Independent Manner in Colon Cancer Cells

    Science.gov (United States)

    Iessi, Elisabetta; Zischler, Luciana; Etringer, Aurélie; Bergeret, Marion; Morlé, Aymeric; Jacquemin, Guillaume; Morizot, Alexandre; Shirley, Sarah; Lalaoui, Najoua; Elifio-Esposito, Selene L.; Fais, Stefano; Garrido, Carmen; Solary, Eric; Micheau, Olivier

    2015-01-01

    Ezrin belongs to the ERM (ezrin-radixin-moesin) protein family and has been demonstrated to regulate early steps of Fas receptor signalling in lymphoid cells, but its contribution to TRAIL-induced cell death regulation in adherent cancer cells remains unknown. In this study we report that regulation of FasL and TRAIL-induced cell death by ezrin is cell type dependant. Ezrin is a positive regulator of apoptosis in T-lymphoma cell line Jurkat, but a negative regulator in colon cancer cells. Using ezrin phosphorylation or actin-binding mutants, we provide evidence that negative regulation of death receptor-induced apoptosis by ezrin occurs in a cytoskeleton- and DISC-independent manner, in colon cancer cells. Remarkably, inhibition of apoptosis induced by these ligands was found to be tightly associated with regulation of ezrin phosphorylation on serine 66, the tumor suppressor gene WWOX and activation of PKA. Deficiency in WWOX expression in the liver cancer SK-HEP1 or the pancreatic Mia PaCa-2 cell lines as well as WWOX silencing or modulation of PKA activation by pharmacological regulators, in the colon cancer cell line SW480, abrogated regulation of TRAIL signalling by ezrin. Altogether our results show that death receptor pro-apoptotic signalling regulation by ezrin can occur downstream of the DISC in colon cancer cells. PMID:26010871

  13. Death Receptor-Induced Apoptosis Signalling Regulation by Ezrin Is Cell Type Dependent and Occurs in a DISC-Independent Manner in Colon Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Elisabetta Iessi

    Full Text Available Ezrin belongs to the ERM (ezrin-radixin-moesin protein family and has been demonstrated to regulate early steps of Fas receptor signalling in lymphoid cells, but its contribution to TRAIL-induced cell death regulation in adherent cancer cells remains unknown. In this study we report that regulation of FasL and TRAIL-induced cell death by ezrin is cell type dependant. Ezrin is a positive regulator of apoptosis in T-lymphoma cell line Jurkat, but a negative regulator in colon cancer cells. Using ezrin phosphorylation or actin-binding mutants, we provide evidence that negative regulation of death receptor-induced apoptosis by ezrin occurs in a cytoskeleton- and DISC-independent manner, in colon cancer cells. Remarkably, inhibition of apoptosis induced by these ligands was found to be tightly associated with regulation of ezrin phosphorylation on serine 66, the tumor suppressor gene WWOX and activation of PKA. Deficiency in WWOX expression in the liver cancer SK-HEP1 or the pancreatic Mia PaCa-2 cell lines as well as WWOX silencing or modulation of PKA activation by pharmacological regulators, in the colon cancer cell line SW480, abrogated regulation of TRAIL signalling by ezrin. Altogether our results show that death receptor pro-apoptotic signalling regulation by ezrin can occur downstream of the DISC in colon cancer cells.

  14. YAP/TAZ enhance mammalian embryonic neural stem cell characteristics in a Tead-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Han, Dasol; Byun, Sung-Hyun; Park, Soojeong; Kim, Juwan; Kim, Inhee; Ha, Soobong; Kwon, Mookwang; Yoon, Keejung, E-mail: keejung@skku.edu

    2015-02-27

    Mammalian brain development is regulated by multiple signaling pathways controlling cell proliferation, migration and differentiation. Here we show that YAP/TAZ enhance embryonic neural stem cell characteristics in a cell autonomous fashion using diverse experimental approaches. Introduction of retroviral vectors expressing YAP or TAZ into the mouse embryonic brain induced cell localization in the ventricular zone (VZ), which is the embryonic neural stem cell niche. This change in cell distribution in the cortical layer is due to the increased stemness of infected cells; YAP-expressing cells were colabeled with Sox2, a neural stem cell marker, and YAP/TAZ increased the frequency and size of neurospheres, indicating enhanced self-renewal- and proliferative ability of neural stem cells. These effects appear to be TEA domain family transcription factor (Tead)–dependent; a Tead binding-defective YAP mutant lost the ability to promote neural stem cell characteristics. Consistently, in utero gene transfer of a constitutively active form of Tead2 (Tead2-VP16) recapitulated all the features of YAP/TAZ overexpression, and dominant negative Tead2-EnR resulted in marked cell exit from the VZ toward outer cortical layers. Taken together, these results indicate that the Tead-dependent YAP/TAZ signaling pathway plays important roles in neural stem cell maintenance by enhancing stemness of neural stem cells during mammalian brain development. - Highlights: • Roles of YAP and Tead in vivo during mammalian brain development are clarified. • Expression of YAP promotes embryonic neural stem cell characteristics in vivo in a cell autonomous fashion. • Enhancement of neural stem cell characteristics by YAP depends on Tead. • Transcriptionally active form of Tead alone can recapitulate the effects of YAP. • Transcriptionally repressive form of Tead severely reduces stem cell characteristics.

  15. YAP/TAZ enhance mammalian embryonic neural stem cell characteristics in a Tead-dependent manner

    International Nuclear Information System (INIS)

    Han, Dasol; Byun, Sung-Hyun; Park, Soojeong; Kim, Juwan; Kim, Inhee; Ha, Soobong; Kwon, Mookwang; Yoon, Keejung

    2015-01-01

    Mammalian brain development is regulated by multiple signaling pathways controlling cell proliferation, migration and differentiation. Here we show that YAP/TAZ enhance embryonic neural stem cell characteristics in a cell autonomous fashion using diverse experimental approaches. Introduction of retroviral vectors expressing YAP or TAZ into the mouse embryonic brain induced cell localization in the ventricular zone (VZ), which is the embryonic neural stem cell niche. This change in cell distribution in the cortical layer is due to the increased stemness of infected cells; YAP-expressing cells were colabeled with Sox2, a neural stem cell marker, and YAP/TAZ increased the frequency and size of neurospheres, indicating enhanced self-renewal- and proliferative ability of neural stem cells. These effects appear to be TEA domain family transcription factor (Tead)–dependent; a Tead binding-defective YAP mutant lost the ability to promote neural stem cell characteristics. Consistently, in utero gene transfer of a constitutively active form of Tead2 (Tead2-VP16) recapitulated all the features of YAP/TAZ overexpression, and dominant negative Tead2-EnR resulted in marked cell exit from the VZ toward outer cortical layers. Taken together, these results indicate that the Tead-dependent YAP/TAZ signaling pathway plays important roles in neural stem cell maintenance by enhancing stemness of neural stem cells during mammalian brain development. - Highlights: • Roles of YAP and Tead in vivo during mammalian brain development are clarified. • Expression of YAP promotes embryonic neural stem cell characteristics in vivo in a cell autonomous fashion. • Enhancement of neural stem cell characteristics by YAP depends on Tead. • Transcriptionally active form of Tead alone can recapitulate the effects of YAP. • Transcriptionally repressive form of Tead severely reduces stem cell characteristics

  16. Measuring Engagement in Fourth to Twelfth Grade Classrooms: The Classroom Engagement Inventory

    Science.gov (United States)

    Wang, Ze; Bergin, Christi; Bergin, David A.

    2014-01-01

    Research on factors that may promote engagement is hampered by the absence of a measure of classroom-level engagement. Literature has suggested that engagement may have 3 dimensions--affective, behavioral, and cognitive. No existing engagement scales measure all 3 dimensions at the classroom level. The Classroom Engagement Inventory (CEI) was…

  17. Work Demands-Burnout and Job Engagement-Job Satisfaction Relationships: Teamwork as a Mediator and Moderator

    OpenAIRE

    Mijakoski, Dragan; Karadzinska-Bislimovska, Jovanka; Basarovska, Vera; Minov, Jordan; Stoleski, Sasho; Angeleska, Nada; Atanasovska, Aneta

    2015-01-01

    BACKGROUND: Few studies have examined teamwork as mediator and moderator of work demands-burnout and job engagement-job satisfaction relationships in healthcare workers (HCWs) in South-East Europe. AIM: To assess mediation and moderation effect of teamwork on the relationship between independent (work demands or job engagement) and dependent (burnout or job satisfaction) variables. METHODS: Work demands, burnout, job engagement, and job satisfaction were measured with Hospital Experienc...

  18. Pragmatic awareness of Suggestions: From (ImPolite Mannerism to Attitudinal Appropriateness

    Directory of Open Access Journals (Sweden)

    Hamid Allami

    2017-09-01

    Full Text Available The present research seeks to determine: (a Iranian EFL learners’ application of suggestion semantic formulae ;(b their attitude of appropriateness in terms of confidence in the employment of appropriate supportive moves; (c, their (impolite mannerism with respect to the selected strategies; and (d the relationship between attitude of appropriateness and mannerism of (impoliteness. An Oxford Quick placement Test (OQPT was administered among 60 Iranian EFL learners to check their language proficiency level and to satisfy the assumption of homogeneity among the learners. These participants along with 10 American native speakers then underwent a suggestion DCT. The questionnaire included questions addressing interlocutors’ with higher, lower or equal power status and intimate or strange social distance. The DCT also involved attitudinal appropriateness scale and (impoliteness mannerism likert scale to examine the learners’ degree of confidence and mannerism. Besides similarities and differences in the application of suggestion semantic formulae between the Iranian learners and American speakers, the results revealed variations in the two groups’ performances for appropriateness and (impoliteness. The results also indicated a positive relationship between the attitude and mannerism scales.

  19. Dynamics from seconds to hours in Hodgkin-Huxley model with time-dependent ion concentrations and buffer reservoirs.

    Directory of Open Access Journals (Sweden)

    Niklas Hübel

    2014-12-01

    Full Text Available The classical Hodgkin-Huxley (HH model neglects the time-dependence of ion concentrations in spiking dynamics. The dynamics is therefore limited to a time scale of milliseconds, which is determined by the membrane capacitance multiplied by the resistance of the ion channels, and by the gating time constants. We study slow dynamics in an extended HH framework that includes time-dependent ion concentrations, pumps, and buffers. Fluxes across the neuronal membrane change intra- and extracellular ion concentrations, whereby the latter can also change through contact to reservoirs in the surroundings. Ion gain and loss of the system is identified as a bifurcation parameter whose essential importance was not realized in earlier studies. Our systematic study of the bifurcation structure and thus the phase space structure helps to understand activation and inhibition of a new excitability in ion homeostasis which emerges in such extended models. Also modulatory mechanisms that regulate the spiking rate can be explained by bifurcations. The dynamics on three distinct slow times scales is determined by the cell volume-to-surface-area ratio and the membrane permeability (seconds, the buffer time constants (tens of seconds, and the slower backward buffering (minutes to hours. The modulatory dynamics and the newly emerging excitable dynamics corresponds to pathological conditions observed in epileptiform burst activity, and spreading depression in migraine aura and stroke, respectively.

  20. Dynamics from seconds to hours in Hodgkin-Huxley model with time-dependent ion concentrations and buffer reservoirs.

    Science.gov (United States)

    Hübel, Niklas; Dahlem, Markus A

    2014-12-01

    The classical Hodgkin-Huxley (HH) model neglects the time-dependence of ion concentrations in spiking dynamics. The dynamics is therefore limited to a time scale of milliseconds, which is determined by the membrane capacitance multiplied by the resistance of the ion channels, and by the gating time constants. We study slow dynamics in an extended HH framework that includes time-dependent ion concentrations, pumps, and buffers. Fluxes across the neuronal membrane change intra- and extracellular ion concentrations, whereby the latter can also change through contact to reservoirs in the surroundings. Ion gain and loss of the system is identified as a bifurcation parameter whose essential importance was not realized in earlier studies. Our systematic study of the bifurcation structure and thus the phase space structure helps to understand activation and inhibition of a new excitability in ion homeostasis which emerges in such extended models. Also modulatory mechanisms that regulate the spiking rate can be explained by bifurcations. The dynamics on three distinct slow times scales is determined by the cell volume-to-surface-area ratio and the membrane permeability (seconds), the buffer time constants (tens of seconds), and the slower backward buffering (minutes to hours). The modulatory dynamics and the newly emerging excitable dynamics corresponds to pathological conditions observed in epileptiform burst activity, and spreading depression in migraine aura and stroke, respectively.

  1. 26 CFR 1.669(b)-2 - Manner of exercising election.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Manner of exercising election. 1.669(b)-2 Section 1.669(b)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... Years Beginning Before January 1, 1969 § 1.669(b)-2 Manner of exercising election. (a) By whom election...

  2. [Peculiarities of silicosis course in women engaged into metallurgy].

    Science.gov (United States)

    Morozova, O A; Morozov, V P; Gorbatovskiĭ, Ia A; Deriabina, N N; Senina, L P

    2011-01-01

    The study covers comparative analysis of silicosis course in males and females engaged into iron industry. Findings are more frequent combination of silicosis and chronic bronchitis in the females, without smoking habit. Some other differences in silicosis course and development were seen dependent on sex.

  3. Social-class indicators differentially predict engagement in prevention vs. detection behaviours.

    Science.gov (United States)

    Haught, Heather M; Rose, Jason P; Brown, Jill A

    2016-01-01

    Few systematic studies have examined the contexts in which social-class variables will predict engagement in health-relevant behaviours. The current research examined whether the impact of social-class on health behaviours depends upon how social-class is assessed and the category of health behaviour under consideration. Our sample was drawn from the Health Information National Trends Survey in 2012 (N = 3959). Participants reported their income and education as well as their engagement in a variety of prevention and detection behaviours. Consistent with our hypothesised framework, we found that income predicted engagement in a variety of detection behaviours above and beyond education, whereas education predicted engagement in a variety of prevention behaviours above and beyond income. Our findings suggest that income and education operate on health behaviours via different pathways and have implications for public health policy and intervention.

  4. How Stakeholder Engagement is Evolving at the Caldas Uranium Mining Site in Minas Gerais, Brazil - 13223

    International Nuclear Information System (INIS)

    Booth, Peter M.; Da Silva, Nivaldo Carlos; Pereira de Oliveira, Alexandre; Cioffi Batagini, Regina Maria; Rangel, Heraldo Junior; Da Conceicao Estrella Abad, Maria

    2013-01-01

    activities on human health and the environment. The main concerns of the local stakeholders were in relation to potential environmental impacts on groundwater and surface water as well as their lack of knowledge about the site's activities and how it might evolve over time. There was a feeling that the site brought no real benefit to the local community as local labor was rarely utilized when work was being undertaken. WSP E and E were asked many questions about stakeholder engagement processes and had to address a number of concerns relating to being able to construct and control an engagement program. Advice was provided on how to construct a phased program in a manner that would allow the site operator to demonstrate increased transparency and allow as wide a range of stakeholders as possible the opportunity to become engaged. We provided an important message in that engagement often had to be culture and project specific and that what might work in one country could not necessarily purely be transposed to another. Since the WSP E and E mission there has been evidence of a number of positive steps in many of the areas of stakeholder engagement related to the Caldas site. The nuclear and environmental regulators work in a more open and transparent manner and continue to undertake joint inspections of the Caldas site. They have agreed to develop a written agreement that will enable them to jointly assess and discuss the issues on the site. Both regulatory bodies had previously accompanied the site operator on a visit to the Wismut uranium mining area in Germany and as well as providing useful learning had also allowed the regulators to discuss some common issues, thus bringing them closer together. A local stakeholder group under the auspices of the Water Commission had previously been set up but now they are starting to have more regular meetings with the site operator and nuclear regulator. They are now additionally considering the formation of a site specific advisory

  5. How Stakeholder Engagement is Evolving at the Caldas Uranium Mining Site in Minas Gerais, Brazil - 13223

    Energy Technology Data Exchange (ETDEWEB)

    Booth, Peter M. [WSP Environment and Energy, Manchester (United Kingdom); Da Silva, Nivaldo Carlos [CNEN, Pocos de Caldas (Brazil); Pereira de Oliveira, Alexandre; Cioffi Batagini, Regina Maria [CMPC, Pocos de Caldas (Brazil); Rangel, Heraldo Junior [INB, Pocos de Caldas (Brazil); Da Conceicao Estrella Abad, Maria [IBAMA, Brasilia (Brazil)

    2013-07-01

    activities on human health and the environment. The main concerns of the local stakeholders were in relation to potential environmental impacts on groundwater and surface water as well as their lack of knowledge about the site's activities and how it might evolve over time. There was a feeling that the site brought no real benefit to the local community as local labor was rarely utilized when work was being undertaken. WSP E and E were asked many questions about stakeholder engagement processes and had to address a number of concerns relating to being able to construct and control an engagement program. Advice was provided on how to construct a phased program in a manner that would allow the site operator to demonstrate increased transparency and allow as wide a range of stakeholders as possible the opportunity to become engaged. We provided an important message in that engagement often had to be culture and project specific and that what might work in one country could not necessarily purely be transposed to another. Since the WSP E and E mission there has been evidence of a number of positive steps in many of the areas of stakeholder engagement related to the Caldas site. The nuclear and environmental regulators work in a more open and transparent manner and continue to undertake joint inspections of the Caldas site. They have agreed to develop a written agreement that will enable them to jointly assess and discuss the issues on the site. Both regulatory bodies had previously accompanied the site operator on a visit to the Wismut uranium mining area in Germany and as well as providing useful learning had also allowed the regulators to discuss some common issues, thus bringing them closer together. A local stakeholder group under the auspices of the Water Commission had previously been set up but now they are starting to have more regular meetings with the site operator and nuclear regulator. They are now additionally considering the formation of a site specific

  6. Lithium concentration dependence of implanted helium retention in lithium silicates

    Energy Technology Data Exchange (ETDEWEB)

    Szocs, D.E., E-mail: szocsd@rmki.kfki.h [KFKI Research Institute for Particle and Nuclear Physics, H-1525 Budapest, P.O. Box 49 (Hungary); Szilagyi, E.; Bogdan, Cs.; Kotai, E. [KFKI Research Institute for Particle and Nuclear Physics, H-1525 Budapest, P.O. Box 49 (Hungary); Horvath, Z.E. [Research Institute for Technical Physics and Materials Science, H-1525 Budapest, P.O. Box 49 (Hungary)

    2010-06-15

    Helium ions of 500 keV were implanted with a fluence of 1.4 x 10{sup 17} ion/cm{sup 2} into various lithium silicates to investigate whether a threshold level of helium retention exists in Li-containing silicate ceramics similar to that found in SiO{sub x} in previous work. The composition and phases of the as prepared lithium silicates were determined by proton backscattering spectrometry (p-BS) and X-ray diffraction (XRD) methods with an average error of {+-}10%. Electrostatic charging of the samples was successfully eliminated by wrapping the samples in Al foil. The amounts of the retained helium within the samples were determined by subtracting the non-implanted spectra from the implanted ones. The experimental results show a threshold in helium retention depending on the Li concentration. Under 20 at.% all He is able to escape from the material; at around 30 at.% nearly half of the He, while over 65 at.% all implanted He is retained. With compositions expressed in SiO{sub 2} volume percentages, a trend similar to those reported of SiO{sub x} previously is found.

  7. P53-dependent ceramide generation in response ro ionizing irradiation is caspase-dependent

    International Nuclear Information System (INIS)

    Dbaibo, G.; El-Assaad, W.

    2000-01-01

    Full text.We have previously reported that p53-dependent apoptosis is accompanied by ceramide accumulation. Lack of p53 prevents ceramide accumulation in response to induces such as ionizing irradiation. The mechanisms of ceramide accumulation have not been explored. P53 has been reported to function by inducing the death receptors Fas and DR5 both of which function by initiating a caspase cascade that results in apoptosis. We decided to examine the role of caspases in the elevation of cellular ceramide levels. We treated Molt-4 cells with 5Gy of ionizing irradiation and examined the effects of co-treatment with the general caspase inhibitor z-VAD-fmk at concentration of 50 and 100μM. We found that z-VAD blocked apoptosis induced by irradiation without interfering with p53 accumulation indicating that it was not functioning upstream of p53. However, z-VAD treatment resulted in a significant decrease in ceramide accumulation. Additionally, z-VAD partially blocked the loss of glutathione in response to irradiation. This was important since glutathione has been described as an inhibitor of neutral sphindomyelinase, a major source of cellular ceramide via sphingomyelin hydrolysis. These studies indicate that p53 induces ceramide accumulation in a caspase-dependent manner and that the regulation of cellular glutathione by caspases may be a mechanism by which they regulate ceramide accumulation

  8. Soft interactions and volume exclusion by polymeric crowders can stabilize or destabilize transient structure in disordered proteins depending on polymer concentration.

    Science.gov (United States)

    Rusinga, Farai I; Weis, David D

    2017-08-01

    The effects of macromolecular crowding on the transient structure of intrinsically disordered proteins is not well-understood. Crowding by biological molecules inside cells could modulate transient structure and alter IDP function. Volume exclusion theory and observations of structured proteins suggest that IDP transient structure would be stabilized by macromolecular crowding. Amide hydrogen exchange (HX) of IDPs in highly concentrated polymer solutions would provide valuable insights into IDP transient structure under crowded conditions. Here, we have used mass spectrometry to measure HX by a transiently helical random coil domain of the activator of thyroid and retinoid receptor (ACTR) in solutions containing 300 g L -1 and 400 g L -1 of Ficoll, a synthetic polysaccharide, using a recently-developed strong cation exchange-based cleanup method [Rusinga, et al., Anal Chem 2017;89:1275-1282]. Transiently helical regions of ACTR exchanged faster in 300 g L -1 Ficoll than in dilute buffer. In contrast, one transient helix exchanged more slowly in 400 g L -1 Ficoll. Nonspecific interactions destabilize ACTR helicity in 300 g L -1 Ficoll because ACTR engages with the Ficoll polymer mesh. In contrast, 400 g L -1 Ficoll is a semi-dilute solution where ACTR cannot engage the Ficoll mesh. At this higher concentration, volume exclusion stabilizes ACTR helicity because ACTR is compacted in interstitial spaces between Ficoll molecules. Our results suggest that the interplay between nonspecific interactions and volume exclusion in different cellular compartments could modulate IDP function by altering the stability of IDP transient structures. Proteins 2017; 85:1468-1479. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. Activity Engagement: Perspectives from Nursing Home Residents with Dementia

    Science.gov (United States)

    Tak, Sunghee H.; Kedia, Satish; Tongumpun, Tera Marie; Hong, Song Hee

    2014-01-01

    Engagement in social and leisure activities is an indicator of quality of life and well-being in nursing homes. There are few studies in which nursing home residents with dementia self-reported their experiences in activity engagement. This qualitative study describes types of current activity involvement and barriers to activities as perceived by nursing home residents with dementia. Thirty-one residents participated in short, open-ended interviews and six in in-depth interviews. Thematic content analysis showed that participants primarily depended on activities organized by their nursing homes. Few participants engaged in self-directed activities such as walking, visiting other residents and family members, and attending in church services. Many residents felt they had limited opportunities and motivation for activities. They missed past hobbies greatly but could not continue them due to lack of accommodation and limitation in physical function. Environmental factors, along with fixed activity schedule, further prevented them from engaging in activities. Residents with dementia should be invited to participate in activity planning and have necessary assistance and accommodation in order to engage in activities that matter to them. Based on the findings, a checklist for individualizing and evaluating activities for persons with dementia is detailed. PMID:25489122

  10. EPR study of concentration dependence in Ce, Ce : La and Ce:Y doped SrF2

    NARCIS (Netherlands)

    Dankert, O.; Vainchtein, David; Datema, H.C.; den Hartog, Hendrik

    1995-01-01

    Experimental results of an EPR-study of the concentration dependence of the doubly integrated intensity and linewidth of the signals associated with tetragonal Ce3+-F--dipoles in Sr1-xCexF2+x, Sr-1-0.005-x Ce0.005LaxF2+0.005+x and Sr-1-0.005-x Ce0.005YxF2+0.005+x are presented. Both show a nonlinear

  11. Uniform TiO2 nanoparticles induce apoptosis in epithelial cell lines in a size-dependent manner.

    Science.gov (United States)

    Sun, Qingqing; Ishii, Takayuki; Kanehira, Koki; Sato, Takeshi; Taniguchi, Akiyoshi

    2017-05-02

    The size of titanium dioxide (TiO 2 ) nanoparticles is a vital parameter that determines their cytotoxicity. However, most reported studies have employed irregular shapes and sizes of TiO 2 nanoparticles, as it is difficult to produce nanoparticles of suitable sizes for research. We produced good model TiO 2 nanoparticles of uniform shape and size for use in studying their cytotoxicity. In this work, spherical, uniform polyethylene glycol-modified TiO 2 (TiO 2 -PEG) nanoparticles of differing sizes (100, 200, and 300 nm) were prepared using the sol-gel method. A size-dependent decrease in cell viability was observed with increasing nanoparticle size. Furthermore, apoptosis was found to be positively associated with nanoparticle size, as evidenced by an increase in caspase-3 activity with increasing nanoparticle size. Larger nanoparticles exhibited higher cellular uptake, suggesting that larger nanoparticles more strongly induce apoptosis. In addition, the cellular uptake of different sizes of nanoparticles was energy dependent, suggesting that there are size-dependent uptake pathways. We found that 100 and 200 nm (but not 300 nm) nanoparticles were taken up via clathrin-mediated endocytosis. These results utilizing uniform nanoparticles suggest that the size-dependent cytotoxicity of nanoparticles involves active cellular uptake, caspase-3 activation, and apoptosis in the epithelial cell line (NCI-H292). These findings will hopefully aid in the future design and safe use of nanoparticles.

  12. Inverse size scaling of the nucleolus by a concentration-dependent phase transition.

    Science.gov (United States)

    Weber, Stephanie C; Brangwynne, Clifford P

    2015-03-02

    Just as organ size typically increases with body size, the size of intracellular structures changes as cells grow and divide. Indeed, many organelles, such as the nucleus [1, 2], mitochondria [3], mitotic spindle [4, 5], and centrosome [6], exhibit size scaling, a phenomenon in which organelle size depends linearly on cell size. However, the mechanisms of organelle size scaling remain unclear. Here, we show that the size of the nucleolus, a membraneless organelle important for cell-size homeostasis [7], is coupled to cell size by an intracellular phase transition. We find that nucleolar size directly scales with cell size in early C. elegans embryos. Surprisingly, however, when embryo size is altered, we observe inverse scaling: nucleolar size increases in small cells and decreases in large cells. We demonstrate that this seemingly contradictory result arises from maternal loading of a fixed number rather than a fixed concentration of nucleolar components, which condense into nucleoli only above a threshold concentration. Our results suggest that the physics of phase transitions can dictate whether an organelle assembles, and, if so, its size, providing a mechanistic link between organelle assembly and cell size. Since the nucleolus is known to play a key role in cell growth, this biophysical readout of cell size could provide a novel feedback mechanism for growth control. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Dose-dependent ATP depletion and cancer cell death following calcium electroporation, relative effect of calcium concentration and electric field strength

    DEFF Research Database (Denmark)

    Hansen, Emilie Louise; Sozer, Esin Bengisu; Romeo, Stefania

    2015-01-01

    death and could be a novel cancer treatment. This study aims at understanding the relationship between applied electric field, calcium concentration, ATP depletion and efficacy. METHODS: In three human cell lines--H69 (small-cell lung cancer), SW780 (bladder cancer), and U937 (leukaemia), viability...... was observed with fluorescence confocal microscopy of quinacrine-labelled U937 cells. RESULTS: Both H69 and SW780 cells showed dose-dependent (calcium concentration and electric field) decrease in intracellular ATP (p...-dependently reduced cell survival and intracellular ATP. Increasing extracellular calcium allows the use of a lower electric field. GENERAL SIGNIFICANCE: This study supports the use of calcium electroporation for treatment of cancer and possibly lowering the applied electric field in future trials....

  14. Human decidual stromal cells secrete soluble pro-apoptotic factors during decidualization in a cAMP-dependent manner.

    Science.gov (United States)

    Leno-Durán, E; Ruiz-Magaña, M J; Muñoz-Fernández, R; Requena, F; Olivares, E G; Ruiz-Ruiz, C

    2014-10-10

    Is there a relationship between decidualization and apoptosis of decidual stromal cells (DSC)? Decidualization triggers the secretion of soluble factors that induce apoptosis in DSC. The differentiation and apoptosis of DSC during decidualization of the receptive decidua are crucial processes for the controlled invasion of trophoblasts in normal pregnancy. Most DSC regress in a time-dependent manner, and their removal is important to provide space for the embryo to grow. However, the mechanism that controls DSC death is poorly understood. The apoptotic response of DSC was analyzed after exposure to different exogenous agents and during decidualization. The apoptotic potential of decidualized DSC supernatants and prolactin (PRL) was also evaluated. DSC lines were established from samples of decidua from first trimester pregnancies. Apoptosis was assayed by flow cytometry. PRL production, as a marker of decidualization, was determined by enzyme-linked immunosorbent assay. DSCs were resistant to a variety of apoptosis-inducing substances. Nevertheless, DSC underwent apoptosis during decidualization in culture, with cAMP being essential for both apoptosis and differentiation. In addition, culture supernatants from decidualized DSC induced apoptosis in undifferentiated DSC, although paradoxically these supernatants decreased the spontaneous apoptosis of decidual lymphocytes. Exogenously added PRL did not induce apoptosis in DSC and an antibody that neutralized the PRL receptor did not decrease the apoptosis induced by supernatants. Further studies are needed to examine the involvement of other soluble factors secreted by decidualized DSC in the induction of apoptosis. The present results indicate that apoptosis of DSC occurs in parallel to differentiation, in response to decidualization signals, with soluble factors secreted by decidualized DSC being responsible for triggering cell death. These studies are relevant in the understanding of how the regression of decidua

  15. Does the amount of school choice matter for student engagement?

    Science.gov (United States)

    Vaughn, Michael G.; Witko, Christopher

    2013-01-01

    School choice may increase student engagement by enabling students to attend schools that more closely match their needs and preferences. But this effect on engagement may depend on the characteristics of the choices available. Therefore, we consider how the amount of educational choice of different types in a local educational marketplace affects student engagement using a large, national population of 8th grade students. We find that more choice of regular public schools in the elementary and middle school years is associated with a lower likelihood that students will be severely disengaged in eighth grade, and more choices of public schools of choice has a similar effect but only in urban areas. In contrast, more private sector choice does not have such a general beneficial effect. PMID:23682202

  16. Longitudinal dispersion with time-dependent source concentration ...

    Indian Academy of Sciences (India)

    industries, especially coal-based industries in the industrial states such as Jharkhand and its neigh- bouring states. These industries ..... of the concentration levels of contaminants with time and distance travel- led, may help to rehabilitate the contaminated aquifer and may be useful for groundwater resource management.

  17. Carrier concentration dependence of donor activation energy in n-type GaN epilayers grown on Si (1 1 1) by plasma-assisted MBE

    International Nuclear Information System (INIS)

    Kumar, Mahesh; Bhat, Thirumaleshwara N.; Roul, Basanta; Rajpalke, Mohana K.; Kalghatgi, A.T.; Krupanidhi, S.B.

    2012-01-01

    Highlights: ► The n-type GaN layers were grown by plasma-assisted molecular beam epitaxy. ► The optical characteristics of a donor level in Si-doped GaN were studied. ► Activation energy of a Si-related donor was estimated from temperature dependent PL measurements. ► PL peak positions, FWHM of PL and activation energies are found to be proportional to the cube root of carrier density. ► The involvement of donor levels is supported by the temperature-dependent electron concentration measurements. -- Abstract: The n-type GaN layers were grown by plasma-assisted MBE and either intentionally doped with Si or unintentionally doped. The optical characteristics of a donor level in Si-doped, GaN were studied in terms of photoluminescence (PL) spectroscopy as a function of electron concentration. Temperature dependent PL measurements allowed us to estimate the activation energy of a Si-related donor from temperature-induced decay of PL intensity. PL peak positions, full width at half maximum of PL and activation energies are found to be proportional to the cube root of carrier density. The involvement of donor levels is supported by the temperature-dependent electron concentration measurements.

  18. Bioreactor design for successive culture of anchorage-dependent cells operated in an automated manner.

    Science.gov (United States)

    Kino-Oka, Masahiro; Ogawa, Natsuki; Umegaki, Ryota; Taya, Masahito

    2005-01-01

    A novel bioreactor system was designed to perform a series of batchwise cultures of anchorage-dependent cells by means of automated operations of medium change and passage for cell transfer. The experimental data on contamination frequency ensured the biological cleanliness in the bioreactor system, which facilitated the operations in a closed environment, as compared with that in flask culture system with manual handlings. In addition, the tools for growth prediction (based on growth kinetics) and real-time growth monitoring by measurement of medium components (based on small-volume analyzing machinery) were installed into the bioreactor system to schedule the operations of medium change and passage and to confirm that culture proceeds as scheduled, respectively. The successive culture of anchorage-dependent cells was conducted with the bioreactor running in an automated way. The automated bioreactor gave a successful culture performance with fair accordance to preset scheduling based on the information in the latest subculture, realizing 79- fold cell expansion for 169 h. In addition, the correlation factor between experimental data and scheduled values through the bioreactor performance was 0.998. It was concluded that the proposed bioreactor with the integration of the prediction and monitoring tools could offer a feasible system for the manufacturing process of cultured tissue products.

  19. Engaging in Productive Sector Development

    DEFF Research Database (Denmark)

    Whitfield, Lindsay; Buur, Lars

    Through a comparison of sector cases in Mozambique and Ghana, the paper analyzes why and how African states engage in developing productive sectors and with what success. It argues that successful state interventions depend on four factors: (1) sustained political support by the government...... in the four factors and thus different economic outcomes. Specifically, cocoa, export is a case of sustained political support, palm oil is a case of poorly implemented industrial policy, and horticulture export is a case of political neglect of an industry. In concluding, the paper emphasizes the political...

  20. Engaging in productive sector development

    DEFF Research Database (Denmark)

    Buur, Lars; Whitfield, Lindsay

    Through a comparison of sector cases in Mozambique and Ghana, the paper analyzes why and how African states engage in developing productive sectors and with what success. It argues that successful state interventions depend on four factors: (1) sustained political support by the government...... in the four factors and thus different economic outcomes. Specifically, cocoa, export is a case of sustained political support, palm oil is a case of poorly implemented industrial policy, and horticulture export is a case of political neglect of an industry. In concluding, the paper emphasizes the political...

  1. Silver Nanoparticles Incite Size and Dose-Dependent Developmental Phenotypes and Nanotoxicity in Zebrafish Embryos

    Science.gov (United States)

    Browning, Lauren M.; Lee, Kerry J.; Nallathamby, Prakash D.; Xu, Xiao-Hong Nancy

    2013-01-01

    Nanomaterials possess distinctive physicochemical properties and promise a wide range of applications, from advanced technology to leading-edge medicine. However, their effects on living organisms remain largely unknown. Here we report that the purified silver nanoparticles (Ag NPs, 97 ± 13 nm) incite specific developmental stage embryonic phenotypes and nanotoxicity in a dose-dependent manner, upon acute exposure of given-stage embryos to the NPs (0–24 pM) for only 2 h. The critical concentrations of the NPs that cause 50% of embryos develop normally for cleavage, early-gastrula, early-segmentation, late-segmentation, and hatching stage zebrafish embryos are 3.5, 4, 6, 6, and 8 pM, respectively, showing that the earlier developmental stage embryos are much more sensitive to the effects of the NPs than the later stage. Interestingly, distinctive phenotypes (head abnormality and no eyes) are observed only in cleavage and early-gastrula stage embryos treated with the NPs, showing the stage-specific effects of the NPs. By comparing with our study of the smaller Ag NPs (13.1 ± 2.5 nm), we found that the embryonic phenotypes strikingly depend upon the sizes of Ag NPs and embryonic developmental stages. These notable findings suggest that the Ag NPs are unlike any conventional chemicals or ions. They can potentially enable target specific study and therapy for early embryonic development in size, stage, dose, and exposure-duration dependent manners. PMID:24024906

  2. Silver nanoparticles incite size- and dose-dependent developmental phenotypes and nanotoxicity in zebrafish embryos.

    Science.gov (United States)

    Browning, Lauren M; Lee, Kerry J; Nallathamby, Prakash D; Xu, Xiao-Hong Nancy

    2013-10-21

    Nanomaterials possess distinctive physicochemical properties and promise a wide range of applications, from advanced technology to leading-edge medicine. However, their effects on living organisms remain largely unknown. Here we report that the purified silver nanoparticles (Ag NPs) (97 ± 13 nm) incite specific developmental stage embryonic phenotypes and nanotoxicity in a dose-dependent manner, upon acute exposure of given stage embryos to the NPs (0-24 pM) for only 2 h. The critical concentrations of the NPs that cause 50% of embryos to develop normally for cleavage, early gastrula, early segmentation, late segmentation, and hatching stage zebrafish embryos are 3.5, 4, 6, 6, and 8 pM, respectively, showing that the earlier developmental stage embryos are much more sensitive to the effects of the NPs than the later stage embryos. Interestingly, distinctive phenotypes (head abnormality and no eyes) are observed only in cleavage and early gastrula stage embryos treated with the NPs, showing the stage-specific effects of the NPs. By comparing these Ag NPs with smaller Ag NPs (13.1 ± 2.5 nm), we found that the embryonic phenotypes strikingly depend upon the sizes of Ag NPs and embryonic developmental stages. These notable findings suggest that the Ag NPs are unlike any conventional chemicals or ions. They can potentially enable target-specific study and therapy for early embryonic development in size-, stage-, dose-, and exposure duration-dependent manners.

  3. Relationship between cobalamin-dependent metabolites and both serum albumin and alpha1 -proteinase inhibitor concentrations in hypocobalaminemic dogs of 7 different breeds.

    Science.gov (United States)

    Grützner, Niels; Suchodolski, Jan S; Steiner, Jörg M

    2014-12-01

    Increased serum concentrations of homocysteine (HCY) and methylmalonic acid (MMA), the 2 main cobalamin-dependent metabolites, as well as decreased serum albumin and canine alpha1 -proteinase inhibitor (cα1 -PI) concentrations have previously been described in hypocobalaminemic dogs with gastrointestinal disease. However, no studies have been conducted to evaluate potential relationships between these serum biomarkers. The aim of this study was to evaluate the relationship between HCY and MMA, 2 cobalamin-dependent metabolites, and both serum albumin and cα1 -PI concentrations in hypocobalaminemic dogs. Serum samples from 285 dogs including 7 different breeds (Beagle, Boxer, Cocker Spaniel, German Shepherd, Labrador Retriever, Chinese Shar-Pei, and Yorkshire Terrier) with hypocobalaminemia were used. Serum HCY, MMA, albumin, and cα1 -PI concentrations were determined. There was a significant correlation between serum HCY and albumin concentrations, as well as serum HCY and cα1 -PI concentrations (ρ = 0.62 and ρ = 0.37, respectively; P  .05). In addition, significant breed-specific correlations were observed between serum MMA and albumin concentrations in German Shepherds, and serum HCY and MMA concentrations in Chinese Shar-Peis with hypocobalaminemia. This study shows a correlation between serum albumin and cα1 -PI and HCY concentrations, but not with serum MMA concentration in dogs with hypocobalaminemia. In addition, significant breed-specific correlations were observed between serum MMA and albumin concentrations in German Shepherds, as well as serum HCY and MMA concentrations in Chinese Shar-Peis, emphasizing the unique metabolic interactions in those dog breeds affected by hypocobalaminemia. © 2014 American Society for Veterinary Clinical Pathology.

  4. The force dependence of isometric and concentric potentiation in mouse muscle with and without skeletal myosin light chain kinase.

    Science.gov (United States)

    Gittings, William; Aggarwal, Harish; Stull, James T; Vandenboom, Rene

    2015-01-01

    The isometric potentiation associated with myosin phosphorylation is force dependent. The purpose of this study was to assess the influence of a pre-existing period of isometric force on the concentric force potentiation displayed by mouse muscles with and without the ability to phosphorylate myosin. We tested isometric (ISO) and concentric (CON) potentiation, as well as concentric potentiation after isometric force (ISO-CON), in muscles from wild-type (WT) and skeletal myosin light chain kinase-deficient (skMLCK(-/-)) mice. A conditioning stimulus increased (i.e., potentiated) mean concentric force in the ISO-CON and CON conditions to 1.31 ± 0.02 and 1.35 ± 0.02 (WT) and to 1.19 ± 0.02 and 1.21 ± 0.01 (skMLCK(-/-)) of prestimulus levels, respectively (data n = 6-8, p muscles.

  5. Engagement of Sectors Other than Health in Integrated Health Governance, Policy, and Action.

    Science.gov (United States)

    de Leeuw, Evelyne

    2017-03-20

    Health is created largely outside the health sector. Engagement in health governance, policy, and intervention development and implementation by sectors other than health is therefore important. Recent calls for building and implementing Health in All Policies, and continued arguments for intersectoral action, may strengthen the potential that other sectors have for health. This review clarifies the conceptual foundations for integral health governance, policy, and action, delineates the different sectors and their possible engagement, and provides an overview of a continuum of methods of engagement with other sectors to secure integration. This continuum ranges from institutional (re)design to value-based narratives. Depending on the lens applied, different elements can be identified within the continuum. This review is built on insights from political science, leadership studies, public health, empirical Health in All Policy research, knowledge and evidence nexus approaches, and community perspectives. Successful integration of health governance, policy, and action depends on integration of the elements on the continuum.

  6. Neuroprotective effect of interleukin-6 regulation of voltage-gated Na+ channels of cortical neurons is time- and dose-dependent

    Directory of Open Access Journals (Sweden)

    Wei Xia

    2015-01-01

    Full Text Available Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorly understood. This study investigated the effects of 24 hour exposure of interleukin-6 on cortical neurons at various concentrations (0.1, 1, 5 and 10 ng/mL and the effects of 10 ng/mL interleukin-6 exposure to cortical neurons for various durations (2, 4, 8, 24 and 48 hours by studying voltage-gated Na + channels using a patch-clamp technique. Voltage-clamp recording results demonstrated that interleukin-6 suppressed Na + currents through its receptor in a time- and dose-dependent manner, but did not alter voltage-dependent activation and inactivation. Current-clamp recording results were consistent with voltage-clamp recording results. Interleukin-6 reduced the action potential amplitude of cortical neurons, but did not change the action potential threshold. The regulation of voltage-gated Na + channels in rat cortical neurons by interleukin-6 is time- and dose-dependent.

  7. Time-Dependent Decline in Serum Phenytoin Concentration with Heightened Convulsive Seizure Risk by Prolonged Administration of Fosphenytoin in Japanese: A Retrospective Study.

    Science.gov (United States)

    Ohno, Yuta; Niwa, Takashi; Hirai, Keita; Suzuki, Keiko; Yamada, Yuto; Hayashi, Yuichi; Hayashi, Hideki; Suzuki, Akio; Itoh, Yoshinori

    2018-04-20

    Because clinical data to confirm the safety and effectiveness of fosphenytoin, a prodrug of phenytoin, are insufficient, the length of administration of fosphenytoin is restricted. Nevertheless, some cases require fosphenytoin administration for more than a few days. The aim of this study was to retrospectively investigate the serum concentration of phenytoin in adult Japanese patients who received intravenous fosphenytoin therapy for more than 3 days. Patients injected with intravenous fosphenytoin for more than 3 days at Gifu University Hospital between January 2012 and September 2014 were enrolled. Individual pharmacokinetic parameters were predicted by Bayesian estimation using NONMEM software, and the maintenance dose of fosphenytoin required to maintain the therapeutic trough concentration (10-20 μg/mL) was calculated from the parameters. Among a total of 8 patients, the serum trough concentration of phenytoin decreased with each day after repeated injection of fosphenytoin. The incidence rate of significant convulsive seizures was increased time-dependently (0% on day 1, 12.5% on day 2, 25% on day 3, and 66.7% on day 4 and after). Phenytoin clearance showed a time-dependent increase. The maintenance dose of fosphenytoin required to maintain the therapeutic trough concentration was simulated to be 779.8 ± 316.8 mg/day, a dose that was markedly higher than the actual maintenance dose (414.1 ± 55.7 mg/day). Prolonged use of fosphenytoin for such patients as those with autoimmune-mediated encephalopathy accompanied with reflux disease and/or ileus time-dependently decreased the serum concentration of phenytoin and increased the risk of convulsion. Therefore, the maintenance dose should be increased to maintain the therapeutic serum concentration.

  8. Ketamine Metabolites Enantioselectively Decrease Intracellular D-Serine Concentrations in PC-12 Cells.

    Directory of Open Access Journals (Sweden)

    Nagendra S Singh

    Full Text Available D-Serine is an endogenous NMDA receptor co-agonist that activates synaptic NMDA receptors modulating neuronal networks in the cerebral cortex and plays a key role in long-term potentiation of synaptic transmission. D-serine is associated with NMDA receptor neurotoxicity and neurodegeneration and elevated D-serine concentrations have been associated with Alzheimer's and Parkinsons' diseases and amyotrophic lateral sclerosis. Previous studies have demonstrated that the ketamine metabolites (rac-dehydronorketamine and (2S,6S-hydroxynorketamine decrease intracellular D-serine concentrations in a concentration dependent manner in PC-12 cells. In the current study, PC-12 cells were incubated with a series of ketamine metabolites and the IC50 values associated with attenuated intracellular D-serine concentrations were determined. The results demonstrate that structural and stereochemical features of the studied compounds contribute to the magnitude of the inhibitory effect with (2S,6S-hydroxynorketamine and (2R,6R-hydroxynorketamine displaying the most potent inhibition with IC50 values of 0.18 ± 0.04 nM and 0.68 ± 0.09 nM. The data was utilized to construct a preliminary 3D-QSAR/pharmacophore model for use in the design of new and more efficient modulators of D-serine.

  9. Knowledge management, health information technology and nurses' work engagement.

    Science.gov (United States)

    Hendriks, Paul H J; Ligthart, Paul E M; Schouteten, Roel L J

    2016-01-01

    Knowledge management (KM) extends the health information technology (HIT) literature by addressing its impact on creating knowledge by sharing and using the knowledge of health care professionals in hospitals. The aim of the study was to provide insight into how HIT affects nurses' explicit and tacit knowledge of their ongoing work processes and work engagement. Data were collected from 74 nurses in four wards of a Dutch hospital via a paper-and-pencil survey using validated measurement instruments. In a quasiexperimental research design, HIT was introduced in the two experimental wards in contrast to the two control wards. At the time of the HIT introduction, a pretest was administered in all four wards and was followed by a posttest after 3 months. Data were analyzed via partial least squares modeling. Generally, nurses' tacit knowledge (i.e., their insight into and their capacity to make sense of the work processes) appears to be a significant and strong predictor of their work engagement. In contrast, nurses' explicit knowledge (i.e., information feedback about patients and tasks) only indirectly affects work engagement via its effect on tacit knowledge. Its effect on work engagement therefore depends on the mediating role of tacit knowledge. Interestingly, introducing HIT significantly affects only nurses' explicit knowledge, not their tacit knowledge or work engagement. Nurses' tacit and explicit knowledge needs to be systematically distinguished when implementing HIT/KM programs to increase work engagement in the workplace. Tacit knowledge (insight into work processes) appears to be pivotal, whereas efforts aimed only at improving available information will not lead to a higher level of work engagement in nurses' work environments.

  10. Determining the size and concentration dependence of gold nanoparticles in vitro cytotoxicity (IC50) test using WST-1 assay

    International Nuclear Information System (INIS)

    Rosli, Nur Shafawati binti; Rahman, Azhar Abdul; Aziz, Azlan Abdul; Shamsuddin, Shaharum

    2015-01-01

    Gold nanoparticles (AuNPs) received a great deal of attention for biomedical applications, especially in diagnostic imaging and therapeutics. Even though AuNPs have potential benefits in biomedical applications, the impact of AuNPs on human and environmental health still remains unclear. The use of AuNPs which is a high-atomic-number materials, provide advantages in terms of radiation dose enhancement. However, before this can become a clinical reality, cytotoxicity of the AuNPs has to be carefully evaluated. Cytotoxicity test is a rapid, standardized test that is very sensitive to determine whether the nanoparticles produced are harmful or benign on cellular components. In this work the size and concentration dependence of AuNPs cytotoxicity in breast cancer cell lines (MCF-7) are tested by using WST-1 assay. The sizes of AuNPs tested were 13 nm, 50 nm, and 70 nm. The cells were seeded in the 96-well plate and were treated with different concentrations of AuNPs by serial dilution for each size of AuNPs. The high concentration of AuNPs exhibit lower cell viability compared to low concentration of AuNPs. We quantified the toxicity of AuNPs in MCF-7 cell lines by determining the IC 50 values in WST-1 assays. The IC 50 values (inhibitory concentrations that effected 50% growth inhibition) of 50 nm AuNPs is lower than 13 nm and 70 nm AuNPs. Mean that, 50nm AuNPs are more toxic to the MCF-7 cells compared to smaller and larger sizes AuNPs. The presented results clearly indicate that the cytotoxicity of AuNPs depend not only on the concentration, but also the size of the nanoparticles

  11. Prenatal stress programs neuroendocrine stress responses and affective behaviors in second generation rats in a sex-dependent manner.

    Science.gov (United States)

    Grundwald, Natalia J; Brunton, Paula J

    2015-12-01

    with controls, with no differences in the F2 females. No differences in depressive-like behavior (sucrose preference or forced swim test) were observed in either sex. In conclusion, the effects of maternal stress during pregnancy on HPA axis regulation and anxiety-like behavior can be transmitted to future generations in a sex-dependent manner. These data have implications for human neuropsychiatric disorders with developmental origins. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Digital Downsides: Exploring University Students' Negative Engagements with Digital Technology

    Science.gov (United States)

    Selwyn, Neil

    2016-01-01

    Digital technologies are now an integral feature of university study. As such, academic research has tended to concentrate on the potential of digital technologies to support, extend and even "enhance" student learning. This paper, in contrast, explores the rather more messy realities of students' engagements with digital technology. In…

  13. Employee engagement: a prescription for organizational transformation.

    Science.gov (United States)

    Halm, Barry

    2011-01-01

    Ivanitskaya, Glazer, and Erofeev (2009) suggest that "the most fundamental element of any organization that helps the organization to survive is the individual person" (p. 109). It is the motivation of human capital that makes a health-care organization come to life. Health-care is a unique industry; its accomplishments are directly dependent upon the competencies and technical skills of its employees. "When people in the workplace fulfill their organizational roles, then the organization thrives" (Ivanitskaya et al., 2009, p. 110). Health-care systems will require organizations that thrive and exhibit characteristics of continuous growth, expressing excessive levels of energy and an immense capacity for flourishing. Anticipating the challenges of the next decade, health-care organizations must achieve a higher degree of employee engagement to enhance organizational performance and profitability. The data analyzed for this chapter indicate that employees who are engaged are more enthusiastic and aspired to achieve both individual and organizational success. The chapter concludes by suggesting five operating practices to establish an employee engagement culture--defining the employee's role in fulfilling the organization's purpose, selecting employees with capability and passion, supporting and valuing the employee, creating sustainable reward systems, and developing feedback and reinforcement mechanisms.

  14. We Engage, Therefore They Trust? A Study of Social Media Engagement and Public Trust in Science

    Science.gov (United States)

    Hwong, Y. L.; Oliver, C.; Van Kranendonk, M. J.

    2017-12-01

    Our society relies heavily on the trust that the public places in science to work. Given science's importance, the growing distrust in science is a cause for concern. Thanks to their participatory nature, social media have been touted as the promising tool for public engagement to restore public trust in science. These digital platforms have transformed the landscape of science communication yet little is known about their impact on public trust in science. This study probed several aspects of public trust in science as expressed on Twitter, focusing on two related science issues: space science and climate change. Our datasets comprised of 10,000 randomly sampled tweets over a month's period in 2016. We used human annotation and machine learning as our approach. Results indicated that the perceived contentiousness of a science issue has a significant impact on public trust. The level of distrust is higher in the climate change tweets than in the space science tweets, despite climate scientists being almost four times as active as space scientists in engaging with sceptics. However, people who engaged with scientists in the climate change network displayed a higher level of trust in science compared with those who did not. This effect was not observed in the space science network - in this network, there is no significant difference in trust levels between people who engaged with scientists and those who did not. Additionally, our machine learning study revealed that trust in science (as conveyed by tweets) can be predicted. The supervised learning algorithm that we developed was able to predict the trust labels of tweets in our sample with an accuracy of 84%. A further feature analysis indicated that similarity, presence of URL and authenticity are the properties of trust-inspiring tweets. Based on these findings, we argue that social media science communication is not as straightforward as `we engage, therefore they trust'. Public attitude towards science is often

  15. Estrogen induced concentration dependent differential gene expression in human breast cancer (MCF7) cells: Role of transcription factors

    International Nuclear Information System (INIS)

    Chandrasekharan, Sabarinath; Kandasamy, Krishna Kumar; Dayalan, Pavithra; Ramamurthy, Viraragavan

    2013-01-01

    Highlights: •Estradiol (E2) at low dose induced cell proliferation in breast cancer cells. •E2 at high concentration induced cell stress in breast cancer cells. •Estrogen receptor physically interacts only with a few transcription factors. •Differential expression of genes with Oct-1 binding sites increased under stress. •Transcription factor binding sites showed distinct spatial distribution on genes. -- Abstract: Background: Breast cancer cells respond to estrogen in a concentration dependent fashion, resulting in proliferation or apoptosis. The mechanism of this concentration dependent differential outcome is not well understood yet. Methodology: Meta-analysis of the expression data of MCF7 cells treated with low (1 nM) or high (100 nM) dose of estradiol (E2) was performed. We identified genes differentially expressed at the low or the high dose, and examined the nature of regulatory elements in the vicinity of these genes. Specifically, we looked for the difference in the presence, abundance and spatial distribution of binding sites for estrogen receptor (ER) and selected transcription factors (TFs) in the genomic region up to 25 kb upstream and downstream from the transcription start site (TSS) of these genes. Results: It was observed that at high dose E2 induced the expression of stress responsive genes, while at low dose, genes involved in cell cycle were induced. We found that the occurrence of transcription factor binding regions (TFBRs) for certain factors such as Sp1 and SREBP1 were higher on regulatory regions of genes expressed at low dose. At high concentration of E2, genes with a higher frequency of Oct-1 binding regions were predominantly involved. In addition, there were differences in the spatial distribution pattern of the TFBRs in the genomic regions among the two sets of genes. Discussion: E2 induced predominantly proliferative/metabolic response at low concentrations; but at high concentration, stress–rescue responses were induced

  16. Estrogen induced concentration dependent differential gene expression in human breast cancer (MCF7) cells: Role of transcription factors

    Energy Technology Data Exchange (ETDEWEB)

    Chandrasekharan, Sabarinath, E-mail: csab@bio.psgtech.ac.in [Department of Biotechnology, PSG College of Technology, Coimbatore 641004 (India); Kandasamy, Krishna Kumar [Max Planck Institute for Biology of Ageing, Cologne (Germany); Dayalan, Pavithra; Ramamurthy, Viraragavan [Department of Biotechnology, PSG College of Technology, Coimbatore 641004 (India)

    2013-08-02

    Highlights: •Estradiol (E2) at low dose induced cell proliferation in breast cancer cells. •E2 at high concentration induced cell stress in breast cancer cells. •Estrogen receptor physically interacts only with a few transcription factors. •Differential expression of genes with Oct-1 binding sites increased under stress. •Transcription factor binding sites showed distinct spatial distribution on genes. -- Abstract: Background: Breast cancer cells respond to estrogen in a concentration dependent fashion, resulting in proliferation or apoptosis. The mechanism of this concentration dependent differential outcome is not well understood yet. Methodology: Meta-analysis of the expression data of MCF7 cells treated with low (1 nM) or high (100 nM) dose of estradiol (E2) was performed. We identified genes differentially expressed at the low or the high dose, and examined the nature of regulatory elements in the vicinity of these genes. Specifically, we looked for the difference in the presence, abundance and spatial distribution of binding sites for estrogen receptor (ER) and selected transcription factors (TFs) in the genomic region up to 25 kb upstream and downstream from the transcription start site (TSS) of these genes. Results: It was observed that at high dose E2 induced the expression of stress responsive genes, while at low dose, genes involved in cell cycle were induced. We found that the occurrence of transcription factor binding regions (TFBRs) for certain factors such as Sp1 and SREBP1 were higher on regulatory regions of genes expressed at low dose. At high concentration of E2, genes with a higher frequency of Oct-1 binding regions were predominantly involved. In addition, there were differences in the spatial distribution pattern of the TFBRs in the genomic regions among the two sets of genes. Discussion: E2 induced predominantly proliferative/metabolic response at low concentrations; but at high concentration, stress–rescue responses were induced

  17. Lethal body concentrations and accumulation patterns determine time-dependent toxicity of cadmium in soil arthropods

    Energy Technology Data Exchange (ETDEWEB)

    Crommentuijn, T.; Doodeman, C.J.A.M.; Doornekamp, A.; Pol, J.J.C. van der; Bedaux, J.J.M.; Gestel, C.A.M. van (Vrije Univ., Amsterdam (Netherlands))

    1994-11-01

    Time-dependent toxicity in bioassays is usually explained in terms of uptake and elimination kinetics of the toxicant. By comparing different species with essentially different accumulation kinetics, a firm test of this concept may be made. This article compares the sensitivity of six soil arthropods, the collembolans Orchesella cincta and Tomocerus minor, the oribatid mite Platynothrus peltifer, the isopods Porcellio scaber and Oniscus asellus, and the diplopod Cylindroiulus britannicus, when exposed to cadmium in the food. Survival was determined at various time intervals; accumulation of cadmium in the animals was measured at one time interval. Kinetic-based toxicity models were fitted to the data, and estimates were obtained for lethal body concentration, uptake rate constant, elimination rate constant, and ultimate LC50. Two different accumulation patterns could be discerned; these were correlated with time-survival relationships. One, species that have the possibility to eliminate cadmium will reach an equilibrium for the internal concentration and also an ultimate LC50. Two, species that are unable to eliminate cadmium but store it in the body will have an ultimate LC50 equal to zero. For these species the time in which the lethal body concentration is reached is more important. Taxonomically related species appeared to have comparable accumulation patterns, but lethal body concentrations differed. It is concluded that knowledge of the accumulation pattern is indispensable for the evaluation of species' sensitivities to toxicants.

  18. Internet use and its impact on engagement in leisure activities in China.

    Science.gov (United States)

    Zhou, Ronggang; Fong, Patrick S W; Tan, Peking

    2014-01-01

    Internet use has become an increasingly common leisure time activity among Chinese citizens. The association between Internet use and engagement in leisure activities is especially unclear among China population. This study aims to investigate Internet usage and to determine whether active Internet use is a marker for low or high levels of leisure time activities. With the use of a face-to-face structured questionnaire interview, a total of 2,400 respondents who met all screening requirements were surveyed to answer the questions in eight major cities in China. 66.2% (n = 1,589) of all respondents were identified as Internet users. Of these Internet users, 30.0%, 24.1%, 26.4%, and 19.6% were clustered as "informative or instrumental users," "entertainment users," "communication users," and "advanced users," respectively. Regarding time spent on Internet use in leisure time, more than 96% reported going online in non-work situations, and 26.2% (n = 416) were classified as "heavy Internet users." A logistic regression analysis revealed that there were significant differences in some leisure activities between non-Internet users and Internet users, with an observed one-unit increase in the leisure time dependence category increasing the probability of engaging in mental or social activities. In contrast, Internet users were less engaged in physical exercise-related activities. In addition, advanced Internet users were generally more active in leisure time activities than non-Internet users and other types of users. Internet use is one of very common leisure activities in Chinese citizens, and age, gender, income, and education are the key factors affecting Internet access. According to different types of leisure activities, Internet usage has different impacts on leisure activity engagement. High Internet dependence has no significant negative influence on engagement in mental or social leisure activities, but this group respondent tended to be less engaged in

  19. Field Dependence-Independence and Physical Activity Engagement among Middle School Students

    Science.gov (United States)

    Liu, Wenhao; Chepyator-Thomson, Jepkorir Rose

    2009-01-01

    Background: Field dependence-independence (FDI) is a tendency to rely on external frames (given situations and authoritative people) or internal frames (oneself, including one's own body) for one's information processing and behavior. Literature has constantly reported that field-dependent (FD) individuals, who are less autonomous in…

  20. Design of 3-D Printed Concentric Tube Robots

    OpenAIRE

    Morimoto, Tania K.; Okamura, Allison M.

    2016-01-01

    Concentric tube surgical robots are minimally invasive devices with the advantages of snake-like reconfigurability, long and thin form factor, and placement of actuation outside the patient’s body. These robots can also be designed and manufactured to acquire targets in specific patients for treating specific diseases in a manner that minimizes invasiveness. We propose that concentric tube robots can be manufactured using 3-D printing technology on a patient- and procedure-specific basis. In ...

  1. In Peer Matters, Teachers Matter: Peer Group Influences on Students' Engagement Depend on Teacher Involvement

    Science.gov (United States)

    Vollet, Justin W.; Kindermann, Thomas A.; Skinner, Ellen A.

    2017-01-01

    This study focused on the joint effects of teachers and peer groups as predictors of change in students' engagement during the first year of middle school, when the importance of peer relationships normatively increases and the quality of teacher-student relationships typically declines. To explore cumulative and contextualized joint effects, the…

  2. Concentration dependent carriers dynamics in CsPbBr3 perovskite nanocrystals film with transient grating

    Science.gov (United States)

    Wang, Yinghui; Wang, Yanting; Dev Verma, Sachin; Tan, Mingrui; Liu, Qinghui; Yuan, Qilin; Sui, Ning; Kang, Zhihui; Zhou, Qiang; Zhang, Han-Zhuang

    2017-05-01

    The concentration dependence of the carrier dynamics is a key parameter to describe the photo-physical properties of semiconductor films. Here, we investigate the carrier dynamics in the CsPbBr3 perovskite nanocrystal film by employing the transient grating (TG) technique with continuous bias light. The concentration of initial carriers is determined by the average number of photons per nanocrystals induced by pump light (⟨N⟩). The multi-body interaction would appear and accelerate the TG dynamics with ⟨N⟩. When ⟨N⟩ is more than 3.0, the TG dynamics slightly changes, which implies that the Auger recombination would be the highest order multi-body interaction in carrier recombination dynamics. The concentration of non-equilibrium carriers in the film is controlled by the average number of photons per nanocrystals excited by continuous bias light (⟨nne⟩). Increasing ⟨nne⟩ would improve the trapping-detrapping process by filling the trapping state, which would accelerate the carrier diffusion and add the complexity of the mono-molecular recombination mechanism. The results should be useful to further understand the mechanism of carrier dynamics in the CsPbBr3 perovskite nanocrystal film and of great importance for the operation of the corresponding optoelectronic devices.

  3. Community Engagement in Youth Violence Prevention: Crafting Methods to Context.

    Science.gov (United States)

    Morrel-Samuels, Susan; Bacallao, Martica; Brown, Shelli; Bower, Meredith; Zimmerman, Marc

    2016-04-01

    The purpose of the Youth Violence Prevention Centers (YVPC) Program at the Centers for Disease Control and Prevention is to reduce youth violence in defined high-risk communities through the implementation and evaluation of comprehensive, evidence based prevention strategies. Within this common framework, each YVPC varies in its structure and methods, however all engage communities in multiple ways. We explore aspects of community engagement employed by three centers that operate in very different contexts: a rural county in North Carolina; a suburban area of Denver, Colorado; and an urban setting in Flint, Michigan. While previous research has addressed theories supporting community involvement in youth violence prevention, there has been less attention to the implementation challenges of achieving and sustaining participation. In three case examples, we describe the foci and methods for community engagement in diverse YVPC sites and detail the barriers and facilitating factors that have influenced implementation. Just as intervention programs may need to be adapted in order to meet the needs of specific populations, methods of community engagement must be tailored to the context in which they occur. We discuss case examples of community engagement in areas with varying geographies, histories, and racial and ethnic compositions. Each setting presents distinct challenges and opportunities for conducting collaborative violence prevention initiatives and for adapting engagement methods to diverse communities. Although approaches may vary depending upon local contexts, there are certain principles that appear to be common across cultures and geography: trust, transparency, communication, commitment. We also discuss the importance of flexibility in community engagement efforts.

  4. Heparin concentration is critical for cell culture with human platelet lysate.

    Science.gov (United States)

    Hemeda, Hatim; Kalz, Jana; Walenda, Gudrun; Lohmann, Michael; Wagner, Wolfgang

    2013-09-01

    Culture media for mesenchymal stromal cells (MSCs) are generally supplemented with fetal bovine serum. Human platelet lysate (hPL) has been proven to be a very effective alternative without the risk of xenogeneic infections or immune reactions. In contrast to fetal bovine serum, hPL comprises plasma, and anticoagulants-usually unfractionated heparin (UFH)-need to be added to prevent gel formation. Cultures of MSCs in hPL media with various concentrations of UFH and enoxaparin, a low-molecular-weight heparin (LMWH), were systematically compared with regard to proliferation, fibroblastoid colony-forming unit frequency, immunophenotype and in vitro differentiation. At least 0.61 IU/mL UFH or 0.024 mg/mL LMWH was necessary for reliable prevention of coagulation of hPL pools used in this study. Higher concentrations impaired cellular proliferation in a dose-dependent manner even without benzyl alcohol, which is commonly added to heparins as a bacteriostatic agent. Colony-forming unit frequency was also reduced at higher heparin concentrations, particularly with LMWH, whereas no significant effect was observed on cellular morphology or immunophenotype. High concentrations of heparins reduced the in vitro differentiation toward adipogenic and osteogenic lineages. Heparin concentration is critical for culture of MSCs in hPL media; this is of particular relevance for cellular therapy where cell culture procedures need to be optimized and standardized. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  5. Simvastatin induces apoptosis by a Rho-dependent mechanism in cultured cardiac fibroblasts and myofibroblasts

    International Nuclear Information System (INIS)

    Copaja, Miguel; Venegas, Daniel; Aranguiz, Pablo; Canales, Jimena; Vivar, Raul; Catalan, Mabel; Olmedo, Ivonne; Rodriguez, Andrea E.; Chiong, Mario; Leyton, Lisette; Lavandero, Sergio; Diaz-Araya, Guillermo

    2011-01-01

    Several clinical trials have shown the beneficial effects of statins in the prevention of coronary heart disease. Additionally, statins promote apoptosis in vascular smooth muscle cells, in renal tubular epithelial cells and also in a variety of cell lines; yet, the effects of statins on cardiac fibroblast and myofibroblast, primarily responsible for cardiac tissue healing are almost unknown. Here, we investigated the effects of simvastatin on cardiac fibroblast and myofibroblast viability and studied the molecular cell death mechanism triggered by simvastatin in both cell types. Methods: Rat neonatal cardiac fibroblasts and myofibroblasts were treated with simvastatin (0.1-10 μM) up to 72 h. Cell viability and apoptosis were evaluated by trypan blue exclusion method and by flow cytometry, respectively. Caspase-3 activation and Rho protein levels and activity were also determined by Western blot and pull-down assay, respectively. Results: Simvastatin induces caspase-dependent apoptosis of cardiac fibroblasts and myofibroblasts in a concentration- and time-dependent manner, with greater effects on fibroblasts than myofibroblasts. These effects were prevented by mevalonate, farnesylpyrophosphate and geranylgeranylpyrophosphate, but not squalene. These last results suggest that apoptosis was dependent on small GTPases of the Rho family rather than Ras. Conclusion: Simvastatin triggered apoptosis of cardiac fibroblasts and myofibroblasts by a mechanism independent of cholesterol synthesis, but dependent of isoprenilation of Rho protein. Additionally, cardiac fibroblasts were more susceptible to simvastatin-induced apoptosis than cardiac myofibroblasts. Thus simvastatin could avoid adverse cardiac remodeling leading to a less fibrotic repair of the damaged tissues. - Research Highlights: → Simvastatin decreases CF and CMF viability independent of cholesterol synthesis. → Simvastatin induces CF and CMF apoptosis in a caspase-dependent manner being CMF more resistant

  6. Modeling steady state SO2-dependent changes in capillary ATP concentration using novel O2 micro-delivery methods

    Science.gov (United States)

    Ghonaim, Nour W.; Fraser, Graham M.; Ellis, Christopher G.; Yang, Jun; Goldman, Daniel

    2013-01-01

    Adenosine triphosphate (ATP) is known to be released from the erythrocyte in an oxygen (O2) dependent manner. Since ATP is a potent vasodilator, it is proposed to be a key regulator in the pathway that mediates micro-vascular response to varying tissue O2 demand. We propose that ATP signaling mainly originates in the capillaries due to the relatively long erythrocyte transit times in the capillary and the short ATP diffusion distance to the electrically coupled endothelium. We have developed a computational model to investigate the effect of delivering or removing O2 to limited areas at the surface of a tissue with an idealized parallel capillary array on total ATP concentration. Simulations were conducted when exposing full surface to perturbations in tissue O2 tension (PO2) or locally using a circular micro-outlet (~100 μm in diameter), a square micro-slit (200 × 200 μm), or a rectangular micro-slit (1000 μm wide × 200 μm long). Results indicated the rectangular micro-slit has the optimal dimensions for altering hemoglobin saturations (SO2) in sufficient number capillaries to generate effective changes in total [ATP]. This suggests a threshold for the minimum number of capillaries that need to be stimulated in vivo by imposed tissue hypoxia to induce a conducted micro-vascular response. SO2 and corresponding [ATP] changes were also modeled in a terminal arteriole (9 μm in diameter) that replaces 4 surface capillaries in the idealized network geometry. Based on the results, the contribution of terminal arterioles to the net change in [ATP] in the micro-vascular network is minimal although they would participate as O2 sources thus influencing the O2 distribution. The modeling data presented here provide important insights into designing a novel micro-delivery device for studying micro-vascular O2 regulation in the capillaries in vivo. PMID:24069001

  7. The Manners of Liberalism: A Question of Limits.

    Science.gov (United States)

    Allen, William B.

    1982-01-01

    The argument that liberal education leads people to substitute intellectual tolerance or ambiguity for righteous indignation is criticized, with reference to Harriet Beecher Stowe's portrayal of Thomas Jefferson, his liberalism, and democratic manners. (MSE)

  8. Metabolic response to MMS-mediated DNA damage in Saccharomyces cerevisiae is dependent on the glucose concentration in the medium.

    Science.gov (United States)

    Kitanovic, Ana; Walther, Thomas; Loret, Marie Odile; Holzwarth, Jinda; Kitanovic, Igor; Bonowski, Felix; Van Bui, Ngoc; Francois, Jean Marie; Wölfl, Stefan

    2009-06-01

    Maintenance and adaptation of energy metabolism could play an important role in the cellular ability to respond to DNA damage. A large number of studies suggest that the sensitivity of cells to oxidants and oxidative stress depends on the activity of cellular metabolism and is dependent on the glucose concentration. In fact, yeast cells that utilize fermentative carbon sources and hence rely mainly on glycolysis for energy appear to be more sensitive to oxidative stress. Here we show that treatment of the yeast Saccharomyces cerevisiae growing on a glucose-rich medium with the DNA alkylating agent methyl methanesulphonate (MMS) triggers a rapid inhibition of respiration and enhances reactive oxygen species (ROS) production, which is accompanied by a strong suppression of glycolysis. Further, diminished activity of pyruvate kinase and glyceraldehyde-3-phosphate dehydrogenase upon MMS treatment leads to a diversion of glucose carbon to glycerol, trehalose and glycogen accumulation and an increased flux through the pentose-phosphate pathway. Such conditions finally result in a significant decline in the ATP level and energy charge. These effects are dependent on the glucose concentration in the medium. Our results clearly demonstrate that calorie restriction reduces MMS toxicity through increased respiration and reduced ROS accumulation, enhancing the survival and recovery of cells.

  9. Detecting positive quadrant dependence and positive function dependence

    NARCIS (Netherlands)

    Janic-Wróblewska, A.; Kallenberg, W.C.M.; Ledwina, T.

    2004-01-01

    There is a lot of interest in positive dependence going beyond linear correlation. In this paper three new rank tests for testing independence against positive dependence are introduced. The first one is directed on positive quadrant dependence, the second and third one concentrate on positive

  10. Detecting positive quadrant dependence and positive function dependence

    NARCIS (Netherlands)

    Janic-Wróblewska, A.; Kallenberg, W.C.M.; Ledwina, T.

    2003-01-01

    There is a lot of interest in positive dependence going beyond linear correlation. In this paper three new rank tests for testing independence against positive dependence are introduced. The first one is directed on positive quadrant dependence, the second and third one concentrate on positive

  11. CTX-M-1 β-lactamase expression in Escherichia coli is dependent on cefotaxime concentration, growth phase and gene location

    DEFF Research Database (Denmark)

    Kjeldsen, Thea S. B.; Overgaard, Martin; Nielsen, Søren S.

    2015-01-01

    blaCTX-M-1 mRNA expression and CTX-M-1 protein levels were dependent on cefotaxime concentration, growth phase and gene location. These results provide insight into the expression of cephalosporin resistance in CTX-M-1-producing E. coli, improving our understanding of the relationship between ant...

  12. [ORGANIZATIONAL COMMITMENT AND WORK ENGAGEMENT - THEORETICAL CONCEPTIONS AND TERMINOLOGICAL PROBLEMS].

    Science.gov (United States)

    Łaguna, Mariola; Mielniczuk, Emilia; Żaliński, Adam; Wałachowska, Karolina

    2015-01-01

    Engagement in professional activities and positive attitudes towards an organization are of significant importance to functioning and health of employees. Studies analysing the phenomena of employees' engagement and their relations with an organization undergo a dynamic development in both international and Polish research. Two theoretical conceptions: organizational commitment (by Meyer and Allen) and work engagement (by Schaufeli and Bakker) have become prominent in the field. They capture 2 similar, albeit distinct constructs. In English-language journals academics concentrate on theoretical and empirical analyses of similarities and differences between the 2 concepts, while in Polish publications scholars also have to deal with the issue of the original term translation. The problem lies mostly in Polish nomenclature of the dimensions proposed in both of these conceptions. Lack of common translations for different studies may cause confusion in this area of research. In the paper authors present a review of Polish translations of terms used in the discussed conceptions and a linguistic analysis of terms, both in English and in Polish. Authors provide solutions which could help to clarify terminology in Polish-language publications concerning organizational commitment and work engagement. This allows for further development of research in this field.

  13. Designing for user engagement

    CERN Document Server

    Geisler, Cheryl

    2013-01-01

    Designing for User Engagement on the Web: 10 Basic Principles is concerned with making user experience engaging. The cascade of social web applications we are now familiar with - blogs, consumer reviews, wikis, and social networking - are all engaging experiences. But engagement is an increasingly common goal in business and productivity environments as well. This book provides a foundation for all those seeking to design engaging user experiences rich in communication and interaction. Combining a handbook on basic principles with case studies, it provides readers with a ric

  14. Protective role of Delphinium denudatum (Jadwar) against morphine induced tolerance and dependence in mice.

    Science.gov (United States)

    Zafar, S; Ahmad, M A; Siddiqui, T A

    2001-11-01

    Chronic treatment with Delphinium denudatum (Dd) (Jadwar) (family: Ranunculaceae, 200-1600 mg/kg) suppressed morphine withdrawal jumps in a dose-dependent manner, a sign of the development of dependence to opiate as assessed by naloxone (2 mg/kg) precipitation withdrawal on day 10 of testing in mice. Repeated administration of Dd (200-1600 mg/kg) for 9 days attenuated the development of tolerance to the analgesic effect of morphine (10 mg/kg), also produces significant change in tail-flick latency from the saline pretreated group in a dose-dependent manner.

  15. THE DEPENDENCE OF GLYCEROL ACCUMULATION AND STARCH HYDROLYZATES FERMENTATION FROM WORT CONCENTRATION

    Directory of Open Access Journals (Sweden)

    Оliynichuk S. Т.

    2015-08-01

    Full Text Available The purpose of this work is to study the dependence of ethanol accumulation by-products and secondary products (glycerol and propionic acid during the fermentation in the case of increasing the wort concentration from 12 to 21% by weight of sugar as an example of commonly used in the alcohol industry the commercial dry yeast company “Danisco” and experimental osmophilic strain Saccharomyces cerevisiae DS-02-E, isolated from a concentrated (80% DM of rye malt wort which spontaneously fermented. The enzyme preparations “AMYLEX 4T”, “ALPHALASE AFP” and “DIAZYME SSF” were used for the liquefaction and saccharification of starch wort. The finished industrial of both yeast strains were added to the fermentation flasks in an amount of 10% by volume of the primary wort. In the mature brew the unfermented carbohydrates content was determined by colorimetric method with anthrone reagent, alcohol — by glass areometer-alcoholometer, acidity — potentiometrically, the concentration of dry matter — by areometer, glycerol content — by photocolorimetry method. In the brew distillate a volatile impurities content, namely propionic acid, was determined using gas chromatography. Statistical processing of the results of three series of experiments were carried out by calculating the arithmetical mean value of 5 measurements, their standard deviations and errors. To determine the probable differences between the mean values were used Student’s t test. Differences were considered statistically significant at P < 0.05. Reduction for accumulation of glycerol (between 38 till 53% at higher concentrations of nutrient medium in the case of the yeast Saccharomyces cerevisiae DS-02-E as compared with commercial dry yeast, reduction the formation of unwanted by-product of fermentation — propionic acid (up to 34%, a better ability of the experimental strain to accumulate sugar of wort and to accumulate ethanol (up to 0.1–0.25% vol. were shown. It

  16. Adaptation and Validation of the Brazilian Version of the Utrecht Work Engagement Scale

    OpenAIRE

    Vazquez, Ana Claudia Souza; Magnan, Emília dos Santos; Pacico, Juliana Cerentini; Hutz, Claudio Simon; Schaufeli, Wilmar B.

    2015-01-01

    Engagement at work is a positive mental and dispositional state characterized by Vigor, Dedication and Concentration. The aim of this study was to adapt and get evidence of validity for the Brazilian version of the utrecht work engagement scale (UWES). Participated in the study 1167 workers between 18 and 70 years (M = 36.8, SD = 10.3) in the Brazilian regions. Studies to establish content and construct validity with the 17- item and the 9- item scales were performed. Exploratory and confirma...

  17. Institutional traditions in teachers' manners of teaching

    Science.gov (United States)

    Lundqvist, Eva; Almqvist, Jonas; Östman, Leif

    2012-03-01

    The aim of this article is to make a close case study of one teacher's teaching in relation to established traditions within science education in Sweden. The teacher's manner of teaching is analysed with the help of an epistemological move analysis. The moves made by the teacher are then compared in a context of educational philosophy and selective tradition. In the analyses the focus is to study the process of teaching and learning in action in institutionalised and socially shared practices. The empirical material consists of video recordings of four lessons with the same group of students and the same teacher. The students are all in Year 7 in a Swedish 9-year compulsory school. During these lessons the students work with a subject area called "Properties of materials". The results show that the teacher makes a number of different moves with regard to how to proceed and come to a conclusion about what the substances are. Many of these moves are special in that they indicate that the students need to be able to handle the procedural level of school science. These moves do not deal directly with the knowledge production process, but with methodological aspects. The function of the moves turns the students' attention from one source of knowledge to another. The moves are aimed at helping the students to help themselves, since it is through their own activity and their own thinking that learning takes place. This is characteristic in the teacher's manner of teaching. When compared in a context of educational philosophy, this manner of teaching has similarities with progressentialism; a mixture of essentialism and progressivism. This educational philosophy is a central aspect of what is called the academic tradition—a selective tradition common in science education in Sweden between 1960 and 1990.

  18. Activity of microemulsion-based nanoparticles at the human bio-nano interface: concentration-dependent effects on thrombosis and hemolysis in whole blood

    International Nuclear Information System (INIS)

    Morey, Timothy E.; Varshney, Manoj; Flint, Jason A.; Seubert, Christoph N.; Smith, W. Brit; Bjoraker, David G.; Shah, Dinesh O.; Dennis, Donn M.

    2004-01-01

    Background: Although microemulsion-based nanoparticles (MEs) may be useful for drug delivery or scavenging, these benefits must be balanced against potential nanotoxicological effects in biological tissue (bio-nano interface). We investigated the actions of assembled MEs and their individual components at the bio-nano interface of thrombosis and hemolysis in human blood.Methods: Oil-in-water MEs were synthesized using ethylbutyrate, sodium caprylate, and pluronic F-68 (ME4) or F-127 (ME6) in 0.9% NaCl w/v . The effects of MEs or components on thrombosis were determined using thrombo-elastography, platelet contractile force, clot elastic modulus, and platelet counting. For hemolysis, ME or components were incubated with erythrocytes, centrifuged, and washed for measurement of free hemoglobin by spectroscopy.Results and conclusions: The mean particle diameters (polydispersity index) for ME6 and ME4 were 23.6 ± 2.5 nm (0.362) and 14.0 ± 1.0 nm (0.008), respectively. MEs (0, 0.03, 0.3, 3 mM) markedly reduced the thromboelastograph maximal amplitude in a concentration-dependent manner (49.0 ± 4.2, 39.0 ± 5.6, 15.0 ± 8.7, 3.8 ± 1.3 mm, respectively), an effect highly correlated (r2 = 0.94) with similar changes caused by pluronic surfactants (48.7 ± 10.9, 30.7 ± 15.8, 20.0 ± 11.3, 2.0 ± 0.5) alone. Neither oil nor sodium caprylate alone affected the thromboelastograph. The clot contractile force was reduced by ME (27.3 ± 11.1-6.7 ± 3.4 kdynes/cm 2 , P = 0.02, n = 5) whereas the platelet population not affected (175 ± 28-182 ± 23 10 6 /ml, P = 0.12, n = 6). This data suggests that MEs reduced platelet activity due to associated pluronic surfactants, but caused minimal changes in protein function necessary for coagulation. Although pharmacological concentrations of sodium caprylate caused hemolysis (EC 50 = 213 mM), MEs and pluronic surfactants did not disrupt erythrocytes. Knowledge of nanoparticle activity and potential associated nanotoxicity at this bio

  19. Activity of microemulsion-based nanoparticles at the human bio-nano interface: concentration-dependent effects on thrombosis and hemolysis in whole blood

    Energy Technology Data Exchange (ETDEWEB)

    Morey, Timothy E.; Varshney, Manoj; Flint, Jason A.; Seubert, Christoph N.; Smith, W. Brit; Bjoraker, David G.; Shah, Dinesh O.; Dennis, Donn M. [University of Florida, Departments of Anesthesiology, Chemical Engineering, and Pharmacology and Experimental Therapeutics, Engineering Research Center for Particle Science and Technology (United States)], E-mail: DDennis@ufl.edu

    2004-06-15

    Background: Although microemulsion-based nanoparticles (MEs) may be useful for drug delivery or scavenging, these benefits must be balanced against potential nanotoxicological effects in biological tissue (bio-nano interface). We investigated the actions of assembled MEs and their individual components at the bio-nano interface of thrombosis and hemolysis in human blood.Methods: Oil-in-water MEs were synthesized using ethylbutyrate, sodium caprylate, and pluronic F-68 (ME4) or F-127 (ME6) in 0.9% NaCl{sub w/v}. The effects of MEs or components on thrombosis were determined using thrombo-elastography, platelet contractile force, clot elastic modulus, and platelet counting. For hemolysis, ME or components were incubated with erythrocytes, centrifuged, and washed for measurement of free hemoglobin by spectroscopy.Results and conclusions: The mean particle diameters (polydispersity index) for ME6 and ME4 were 23.6 {+-} 2.5 nm (0.362) and 14.0 {+-} 1.0 nm (0.008), respectively. MEs (0, 0.03, 0.3, 3 mM) markedly reduced the thromboelastograph maximal amplitude in a concentration-dependent manner (49.0 {+-} 4.2, 39.0 {+-} 5.6, 15.0 {+-} 8.7, 3.8 {+-} 1.3 mm, respectively), an effect highly correlated (r2 = 0.94) with similar changes caused by pluronic surfactants (48.7 {+-} 10.9, 30.7 {+-} 15.8, 20.0 {+-} 11.3, 2.0 {+-} 0.5) alone. Neither oil nor sodium caprylate alone affected the thromboelastograph. The clot contractile force was reduced by ME (27.3 {+-} 11.1-6.7 {+-} 3.4 kdynes/cm{sup 2}, P = 0.02, n = 5) whereas the platelet population not affected (175 {+-} 28-182 {+-} 23 10{sup 6}/ml, P = 0.12, n = 6). This data suggests that MEs reduced platelet activity due to associated pluronic surfactants, but caused minimal changes in protein function necessary for coagulation. Although pharmacological concentrations of sodium caprylate caused hemolysis (EC{sub 50} = 213 mM), MEs and pluronic surfactants did not disrupt erythrocytes. Knowledge of nanoparticle activity and

  20. 21-O-Angeloyltheasapogenol E3, a Novel Triterpenoid Saponin from the Seeds of Tea Plants, Inhibits Macrophage-Mediated Inflammatory Responses in a NF-κB-Dependent Manner

    Directory of Open Access Journals (Sweden)

    Woo Seok Yang

    2014-01-01

    Full Text Available 21-O-Angeloyltheasapogenol E3 (ATS-E3 is a triterpenoid saponin recently isolated from the seeds of the tea tree Camellia sinensis (L. O. Kuntze. ATS-E3 has several beneficial properties including anti-inflammatory, antidiabetic, antiatherosclerotic, and anticancer effects. Unlike other phenolic compounds isolated from tea plants, there are no studies reporting the pharmacological action of ATS-E3. In this study, we therefore aimed to explore the cellular and molecular inhibitory activities of ATS-E3 in macrophage-mediated inflammatory responses. ATS-E3 remarkably diminished cellular responses of macrophages such as FITC-dextran-induced phagocytic uptake, sodium nitroprusside- (SNP- induced radical generation, and LPS-induced nitric oxide (NO production. Analysis of its molecular activity showed that this compound significantly suppressed the expression of inducible NO synthase (iNOS, nuclear translocation of nuclear factor- (NF- κB subunits (p50 and p65, phosphorylation of inhibitor of κB kinase (IKK, and the enzyme activity of AKT1. Taken together, the novel triterpenoid saponin compound ATS-E3 contributes to the beneficial effects of tea plants by exerting anti-inflammatory and antioxidative activities in an AKT/IKK/NF-κB-dependent manner.

  1. Chloride concentrations in human hepatic cytosol and mitochondria are a function of age.

    Science.gov (United States)

    Jahn, Stephan C; Rowland-Faux, Laura; Stacpoole, Peter W; James, Margaret O

    2015-04-10

    We recently reported that, in a concentration-dependent manner, chloride protects hepatic glutathione transferase zeta 1 from inactivation by dichloroacetate, an investigational drug used in treating various acquired and congenital metabolic diseases. Despite the importance of chloride ions in normal physiology, and decades of study of chloride transport across membranes, the literature lacks information on chloride concentrations in animal tissues other than blood. In this study we measured chloride concentrations in human liver samples from male and female donors aged 1 day to 84 years (n = 97). Because glutathione transferase zeta 1 is present in cytosol and, to a lesser extent, in mitochondria, we measured chloride in these fractions by high-performance liquid chromatography analysis following conversion of the free chloride to pentafluorobenzylchloride. We found that chloride concentration decreased with age in hepatic cytosol but increased in liver mitochondria. In addition, chloride concentrations in cytosol, (105.2 ± 62.4 mM; range: 24.7-365.7 mM) were strikingly higher than those in mitochondria (4.2 ± 3.8 mM; range 0.9-22.2 mM). These results suggest a possible explanation for clinical observations seen in patients treated with dichloroacetate, whereby children metabolize the drug more rapidly than adults following repeated doses, and also provide information that may influence our understanding of normal liver physiology. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Overexpression of Drosophila frataxin triggers cell death in an iron-dependent manner.

    Science.gov (United States)

    Edenharter, Oliver; Clement, Janik; Schneuwly, Stephan; Navarro, Juan A

    2017-12-01

    Friedreich ataxia (FRDA) is the most important autosomal recessive ataxia in the Caucasian population. FRDA patients display severe neurological and cardiac symptoms that reflect a strong cellular and axonal degeneration. FRDA is caused by a loss of function of the mitochondrial protein frataxin which impairs the biosynthesis of iron-sulfur clusters and in turn the catalytic activity of several enzymes in the Krebs cycle and the respiratory chain leading to a diminished energy production. Although FRDA is due to frataxin depletion, overexpression might also be very helpful to better understand cellular functions of frataxin. In this work, we have increased frataxin expression in neurons to elucidate specific roles that frataxin might play in these tissues. Using molecular, biochemical, histological and behavioral methods, we report that frataxin overexpression is sufficient to increase oxidative phosphorylation, modify mitochondrial morphology, alter iron homeostasis and trigger oxidative stress-dependent cell death. Interestingly, genetic manipulation of mitochondrial iron metabolism by silencing mitoferrin successfully improves cell survival under oxidative-attack conditions, although enhancing antioxidant defenses or mitochondrial fusion failed to ameliorate frataxin overexpression phenotypes. This result suggests that cell degeneration is directly related to enhanced incorporation of iron into the mitochondria. Drosophila frataxin overexpression might also provide an alternative approach to identify processes that are important in FRDA such as changes in mitochondrial morphology and oxidative stress induced cell death.

  3. Anatase phase stability and doping concentration dependent refractivity in codoped transparent conducting TiO2 films

    International Nuclear Information System (INIS)

    Chen, T L; Furubayashi, Y; Hirose, Y; Hitosugi, T; Shimada, T; Hasegawa, T

    2007-01-01

    Nb 0.06 Sn x Ti 0.94-x O 2 (x ≤ 0.3) thin films were grown by a pulsed-laser deposition method with varying Sn concentration. Through a combinatorial technique, we find that Sn concentration can reach a maximum of about x = 0.3 while maintaining the stable anatase phase and epitaxy. A doping concentration dependence of the refractivity is revealed, in which refractivity reduction at a wavelength of λ = 500 nm is estimated to be 12.4% for Nb 0.06 Sn 0.3 Ti 0.64 O 2 thin film. Sn doping induced band-gap blue shift can be contributed to the mixing of extended Sn 5s orbitals with the conduction band of TiO 2 . Low resistivity on the order of 10 -4 Ω cm at room temperature and high internal transmittance of more than 95% in the visible light region are exhibited for Nb 0.06 Sn x Ti 0.94-x O 2 thin films (x ≤ 0.2). Optical and transport analyses demonstrate that doping Sn into Nb 0.06 Ti 0.94 O 2 can reduce the refractivity while maintaining low resistivity and high transparency

  4. Development of a novel method to determine the concentration of heavy metal cations: application of the specific interaction between heavy metal cation and mismatch DNA base pair.

    Science.gov (United States)

    Kozasa, Tetsuo; Miyakawa, Yukako; Fukushi, Miyako; Ono, Akira; Torigoe, Hidetaka

    2009-01-01

    We have already found that Hg(II) cation specifically binds to T:T mismatch base pair in heteroduplex DNA, which increases the melting temperature of heteroduplex DNA involving T:T mismatch base pair by about 4 degrees C. We have also found that Ag(I) cation specifically binds to C:C mismatch base pair in heteroduplex DNA, which increases the melting temperature of heteroduplex DNA involving C:C mismatch base pair by about 4 degrees C. Using the specific interaction, we developed a novel sensor to determine the concentration of each of Hg(II) and Ag(I) cation. The sensor is composed of a dye-labelled T-rich or C-rich DNA oligonucleotide, F2T6W2D: 5'-Fam-T(2)CT(2)CT(2)C(4)T(2)GT(2)GT(2)-Dabcyl-3' or F2C6W2D: 5'-Fam-C(2)TC(2)TC(2)T(4)C(2)AC(2)AC(2)-Dabcyl-3', where 6-carboxyfluorescein (Fam) is a fluorophore and Dabcyl is a quencher. The addition of Hg(II) cation decreased the intensity of Fam emission of F2T6W2D at 520 nm in a concentration-dependent manner. Also, the addition of Ag(I) cation decreased the intensity of Fam emission of F2C6W2D at 520 nm in a concentration-dependent manner. We conclude that, using the novel sensor developed in this study, the concentration of each of Hg(II) and Ag(I) cation can be determined from the intensity of Fam emission at 520 nm.

  5. Concentration dependence of the partial volume, viscosity, and electric conductivity of solutions of lithium salts in aliphatic alcohols

    International Nuclear Information System (INIS)

    Eliseeva, O.V.; Golubev, V.V.

    2003-01-01

    Concentration dependence of partial volumes, electric conductivity and viscosity of lithium nitrate and chloride solutions in methanol, propanol, isopropanol, butanol, isobutanol, pentanol and isopentanol at 298.15 K were studied by the methods of densimetry, conductometry and viscosimetry. Structural specific features of the solutions studied are discussed on the basis of the calculated volumetric characteristics of the substance dissolved and solvent [ru

  6. Rethinking cell-cycle-dependent gene expression in Schizosaccharomyces pombe.

    Science.gov (United States)

    Cooper, Stephen

    2017-11-01

    Three studies of gene expression during the division cycle of Schizosaccharomyces pombe led to the proposal that a large number of genes are expressed at particular times during the S. pombe cell cycle. Yet only a small fraction of genes proposed to be expressed in a cell-cycle-dependent manner are reproducible in all three published studies. In addition to reproducibility problems, questions about expression amplitudes, cell-cycle timing of expression, synchronization artifacts, and the problem with methods for synchronizing cells must be considered. These problems and complications prompt the idea that caution should be used before accepting the conclusion that there are a large number of genes expressed in a cell-cycle-dependent manner in S. pombe.

  7. Conditional internalization of PEGylated nanomedicines by PEG engagers for triple negative breast cancer therapy

    Science.gov (United States)

    Su, Yu-Cheng; Burnouf, Pierre-Alain; Chuang, Kuo-Hsiang; Chen, Bing-Mae; Cheng, Tian-Lu; Roffler, Steve R.

    2017-06-01

    Triple-negative breast cancer (TNBC) lacks effective treatment options due to the absence of traditional therapeutic targets. The epidermal growth factor receptor (EGFR) has emerged as a promising target for TNBC therapy because it is overexpressed in about 50% of TNBC patients. Here we describe a PEG engager that simultaneously binds polyethylene glycol and EGFR to deliver PEGylated nanomedicines to EGFR+ TNBC. The PEG engager displays conditional internalization by remaining on the surface of TNBC cells until contact with PEGylated nanocarriers triggers rapid engulfment of nanocargos. PEG engager enhances the anti-proliferative activity of PEG-liposomal doxorubicin to EGFR+ TNBC cells by up to 100-fold with potency dependent on EGFR expression levels. The PEG engager significantly increases retention of fluorescent PEG probes and enhances the antitumour activity of PEGylated liposomal doxorubicin in human TNBC xenografts. PEG engagers with specificity for EGFR are promising for improved treatment of EGFR+ TNBC patients.

  8. To make or buy patient safety solutions: a resource dependence and transaction cost economics perspective.

    Science.gov (United States)

    Fareed, Naleef; Mick, Stephen S

    2011-01-01

    For almost a decade, public and private organizations have pressured hospitals to improve their patient safety records. Since 2008, the Centers for Medicare & Medicaid Services has no longer been reimbursing hospitals for secondary diagnoses not reported during the point of admission. This ruling has motivated some hospitals to engage in safety-oriented programs to decrease adverse events. This study examined which hospitals may engage in patient safety solutions and whether they create these patient safety solutions within their structures or use suppliers in the market. We used a theoretical model that incorporates the key constructs of resource dependence theory and transaction cost economics theory to predict a hospital's reaction to Centers for Medicare & Medicaid Services "never event" regulations. We present propositions that speculate on how forces conceptualized from the resource dependence theory may affect adoption of patient safety innovations and, when they do, whether the adopting hospitals will do so internally or externally according to the transaction cost economics theory. On the basis of forces identified by the resource dependence theory, we predict that larger, teaching, safety net, horizontally integrated, highly interdependent, and public hospitals in concentrated, high public payer presence, competitive, and resource-rich environments will be more likely to engage in patient safety innovations. Following the logic of the transaction cost economics theory, we predict that of the hospitals that react positively to the never event regulation, most will internalize their innovations in patient safety solutions rather than approach the market, a choice that helps hospitals economize on transaction costs. This study helps hospital managers in their strategic thinking and planning in relation to current and future regulations related to patient safety. For researchers and policy analysts, our propositions provide the basis for empirical testing.

  9. The ABCs of Student Engagement

    Science.gov (United States)

    Parsons, Seth A.; Nuland, Leila Richey; Parsons, Allison Ward

    2014-01-01

    Student engagement is an important consideration for teachers and administrators because it is explicitly associated with achievement. What the authors call the ABC's of engagement they outline as: Affective engagement, Behavioral engagement, and Cognitive engagement. They also present "Three Things Every Teacher Needs to Know about…

  10. Determining the size and concentration dependence of gold nanoparticles in vitro cytotoxicity (IC{sub 50}) test using WST-1 assay

    Energy Technology Data Exchange (ETDEWEB)

    Rosli, Nur Shafawati binti; Rahman, Azhar Abdul [School of Physics, Universiti Sains Malaysia, 11800, Pulau Pinang (Malaysia); Aziz, Azlan Abdul [School of Physics, Universiti Sains Malaysia, 11800, Pulau Pinang (Malaysia); Nano-Biotechnology Research and Innovation (NanoBRI), Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 11800, Pulau Pinang (Malaysia); Shamsuddin, Shaharum [Nano-Biotechnology Research and Innovation (NanoBRI), Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 11800, Pulau Pinang (Malaysia); School of Health Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan (Malaysia)

    2015-04-24

    Gold nanoparticles (AuNPs) received a great deal of attention for biomedical applications, especially in diagnostic imaging and therapeutics. Even though AuNPs have potential benefits in biomedical applications, the impact of AuNPs on human and environmental health still remains unclear. The use of AuNPs which is a high-atomic-number materials, provide advantages in terms of radiation dose enhancement. However, before this can become a clinical reality, cytotoxicity of the AuNPs has to be carefully evaluated. Cytotoxicity test is a rapid, standardized test that is very sensitive to determine whether the nanoparticles produced are harmful or benign on cellular components. In this work the size and concentration dependence of AuNPs cytotoxicity in breast cancer cell lines (MCF-7) are tested by using WST-1 assay. The sizes of AuNPs tested were 13 nm, 50 nm, and 70 nm. The cells were seeded in the 96-well plate and were treated with different concentrations of AuNPs by serial dilution for each size of AuNPs. The high concentration of AuNPs exhibit lower cell viability compared to low concentration of AuNPs. We quantified the toxicity of AuNPs in MCF-7 cell lines by determining the IC{sub 50} values in WST-1 assays. The IC{sub 50} values (inhibitory concentrations that effected 50% growth inhibition) of 50 nm AuNPs is lower than 13 nm and 70 nm AuNPs. Mean that, 50nm AuNPs are more toxic to the MCF-7 cells compared to smaller and larger sizes AuNPs. The presented results clearly indicate that the cytotoxicity of AuNPs depend not only on the concentration, but also the size of the nanoparticles.

  11. “The Rules of Engagement”: Student Engagement and Motivation to Improve the Quality of Undergraduate Learning

    Directory of Open Access Journals (Sweden)

    Rowena M. Senior

    2018-05-01

    Full Text Available Studying at university continues to grow in popularity and the modern-day university has expanded considerably to meet this need. Invariably as such expansion occurs pressures arise on a range of quality enhancement processes. This may have serious implications for the continued delivery of high quality learning experiences that both meet the expectations of incoming students and are appropriate to their postgraduation aspirations. Ensuring students become active partners in their learning will encourage them to engage with a range of quality enhancement processes. The aim of the current work is to examine the various factors that motivate students to engage in such a fashion. Three focus groups were carried out in a stratified manner to ascertain student motivations and to triangulate an effective set of recommendations for subsequent practice. The participants consisted of engaged and non-engaged first year undergraduate students as well as student-facing staff who were asked to comment on their experiences as to why students would want to engage as a course representative. Nominal group technique was applied to the emerging thematic data in each group. Three key motivational themes emerged that overlapped across all focus groups i.e., a need for individual representation that makes a change, a desire to develop a professional skillset as well as a desire to gain a better understanding of their course of study. A university that aligns its student experience along these themes is likely to facilitate student representation. As is standard practice recommendations for future work are described alongside a discussion of the limitations.

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

    Science.gov (United States)

    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.

  13. Engaging with Assessment: Increasing Student Engagement through Continuous Assessment

    Science.gov (United States)

    Holmes, Naomi

    2018-01-01

    Student engagement is intrinsically linked to two important metrics in learning: student satisfaction and the quality of the student experience. One of the ways that engagement can be influenced is through careful curriculum design. Using the knowledge that many students are "assessment-driven," a low-stakes continuous weekly summative…

  14. Ethanol concentration-dependent alterations in gene expression during acute binge drinking in the HIV-1 transgenic rat.

    Science.gov (United States)

    Sarkar, Sraboni; Chang, Sulie L

    2013-07-01

    Binge drinking of high ethanol (EtOH) concentration beverages is common among young adults and can be a risk factor for exposure to sexually transmitted diseases, including HIV-1. We used a novel noninfectious HIV-1 transgenic (HIV-1Tg) rat model that mimics HIV-1 patients in terms of altered immune responses and deficits in cognitive learning and memory to investigate EtOH concentration-dependent effects on 48 alcohol-modulated genes during binge EtOH administration. HIV-1Tg and control F344 rats were administered water, 8% EtOH, or 52% EtOH by gavage (i.g.) for 3 days (2.0 g/kg/d). Two hours after final treatment, blood, liver, and spleen were collected from each animal. Serum blood EtOH concentration (BEC) was measured, and gene expression in the liver and spleen was determined using a specifically designed PCR array. The BEC was significantly higher in the 52% EtOH-treated HIV-1Tg rats compared with the 8% EtOH group; however, the BEC was higher in the 8% EtOH-treated control rats compared with the 52% EtOH group. There was no change in expression of the EtOH metabolism-related genes, Adh1, Adh4, and Cyp2e1, in either the 8 or 52% EtOH-treated HIV-1Tg rats, whereas expression of those genes was significantly higher in the liver of the 52% EtOH control rats, but not in the 8% EtOH group. In the HIV-1Tg rats, expression of the GABAA , metabotropic glutamate, and dopamine neurotransmitter receptor genes was significantly increased in the spleen of the 52% EtOH group, but not in the 8% EtOH group, whereas no change was observed in those genes in either of the control groups. Our data indicate that, in the presence of HIV-1 infection, EtOH concentration-dependent binge drinking can have significantly different molecular effects. Copyright © 2013 by the Research Society on Alcoholism.

  15. Queer as F**k: reaching and engaging gay men in sexual health promotion through social networking sites.

    Science.gov (United States)

    Pedrana, Alisa; Hellard, Margaret; Gold, Judy; Ata, Nadine; Chang, Shanton; Howard, Steve; Asselin, Jason; Ilic, Olivia; Batrouney, Colin; Stoove, Mark

    2013-02-07

    A growing number of health promotion interventions are taking advantage of the popularity and interactivity of new social media platforms to foster and engage communities for health promotion. However, few health promotion interventions using social networking sites (SNS) have been rigorously evaluated. "Queer as F**k"(QAF) began as pilot project in 2010 to deliver sexual health promotion via short "webisodes" on SNS to gay men. Now in its fifth season, QAF is among the few published examples internationally to demonstrate the sexual health promotion potential of SNS. The objective of this evaluation is to assess reach, interactivity, and engagement generated by QAF to inform future health interventions and evaluations using SNS. We undertook a mixed method process evaluation using an uncontrolled longitudinal study design that compared multiple measurements over time to assess changes in reach and engagement. We adapted evaluation methods from the health promotion, information systems, and creative spheres. We incorporated online usage statistics, interviews informed by user diary-scrapbooks, and user focus groups to assess intervention reach and engagement. During Series 1-3 (April 2010 to April 2011), 32 webisodes were posted on the QAF Facebook and YouTube pages. These webisodes attracted over 30,000 views; ranging from 124-3092 views per individual episode. By April 2011, the QAF Facebook page had 2929 predominantly male fans. Interview and focus group participants supported the balance of education and entertainment. They endorsed the narrative "soap opera" format as an effective way to deliver sexual health messages in an engaging, informative, and accessible manner that encouraged online peer discussion of sexual health and promoted community engagement. QAF offers a successful example of exploiting the reach, interactivity, and engagement potential of SNS; findings from this process evaluation provide a model to inform the delivery and evaluation of future

  16. Low oxygen atmosphere facilitates proliferation and maintains undifferentiated state of umbilical cord mesenchymal stem cells in an hypoxia inducible factor-dependent manner.

    Science.gov (United States)

    Drela, Katarzyna; Sarnowska, Anna; Siedlecka, Patrycja; Szablowska-Gadomska, Ilona; Wielgos, Miroslaw; Jurga, Marcin; Lukomska, Barbara; Domanska-Janik, Krystyna

    2014-07-01

    As we approach the era of mesenchymal stem cell (MSC) application in the medical clinic, the standarization of their culture conditions are of the particular importance. We re-evaluated the influences of oxygens concentration on proliferation, stemness and differentiation of human umbilical cord Wharton Jelly-derived MSCs (WJ-MSCs). Primary cultures growing in 21% oxygen were either transferred into 5% O2 or continued to grow under standard 21% oxygen conditions. Cell expansion was estimated by WST1/enzyme-linked immunosorbent assay or cell counting. After 2 or 4 weeks of culture, cell phenotypes were evaluated using microscopic, immunocytochemical, fluorescence-activated cell-sorting and molecular methods. Genes and proteins typical of mesenchymal cells, committed neural cells or more primitive stem/progenitors (Oct4A, Nanog, Rex1, Sox2) and hypoxia inducible factor (HIF)-1α-3α were evaluated. Lowering O2 concentration from 21% to the physiologically relevant 5% level substantially affected cell characteristics, with induction of stemness-related-transcription-factor and stimulation of cell proliferative capacity, with increased colony-forming unit fibroblasts (CFU-F) centers exerting OCT4A, NANOG and HIF-1α and HIF-2α immunoreactivity. Moreover, the spontaneous and time-dependent ability of WJ-MSCs to differentiate into neural lineage under 21% O2 culture was blocked in the reduced oxygen condition. Importantly, treatment with trichostatin A (TSA, a histone deacetylase inhibitor) suppressed HIF-1α and HIF-2α expression, in addition to blockading the cellular effects of reduced oxygen concentration. A physiologically relevant microenvironment of 5% O2 rejuvenates WJ-MSC culture toward less-differentiated, more primitive and faster-growing phenotypes with involvement of HIF-1α and HIF-2α-mediated and TSA-sensitive chromatin modification mechanisms. These observations add to the understanding of MSC responses to defined culture conditions, which is the most

  17. Effect of donepezil hydrochloride (E2020) on extracellular acetylcholine concentration in the cerebral cortex of rats.

    Science.gov (United States)

    Kosasa, T; Kuriya, Y; Yamanishi, Y

    1999-10-01

    Donepezil hydrochloride (donepezil), a potent and selective acetylcholinesterase inhibitor, has been developed for the treatment of Alzheimer's disease. We studied the effect of oral administration of this drug on the extracellular acetylcholine (ACh) concentration in the cerebral cortex of rats using microdialysis. We also observed fasciculation, a peripheral cholinergic sign induced by activation of neuromuscular transmission, after oral administration of the drug as an index of peripheral cholinergic activation. Other cholinesterase inhibitors, tacrine, ENA-713 and TAK-147, were used as reference drugs. Donepezil significantly and dose-dependently increased the extracellular ACh concentration in the rat cerebral cortex within the dose range of 2.5-10 mg/kg. Tacrine, ENA-713 and TAK-147 also elevated the extracellular concentration of ACh. The minimum effective doses of donepezil, tacrine, ENA-713 and TAK-147 were (< or = 2.5, 10, 10 and < or = 10 mg/kg, respectively. Donepezil produced fasciculation at doses of 2.5 mg/kg and above, with a dose-dependent increase in incidence and intensity. The reference compounds also induced fasciculation in a dose-dependent manner. The threshold doses of tacrine, ENA-713 and TAK-147 for fasciculation were 5, 2.5 and 2.5 mg/kg, respectively. The values of the ratio of the minimum effective dose for the ACh-increasing action to that for the fasciculation-producing action were: donepezil, < or = 1; tacrine, 2; ENA-713, 4; TAK-147, < or = 4. These results indicate that orally administered donepezil has a potent and selective activity on the central cholinergic system.

  18. University student’s engagement: development of the University Student Engagement Inventory (USEI

    Directory of Open Access Journals (Sweden)

    João Maroco

    2016-01-01

    Full Text Available Abstract Student engagement is a key factor in academic achievement and degree completion, though there is much debate about the operationalization and dimensionality of this construct. The goal of this paper is to describe the development of an psycho-educational oriented measure – the University Student Engagement Inventory (USEI. This measure draws on the conceptualization of engagement as a multidimensional construct, including cognitive, behavioural and emotional engagement. Participants were 609 Portuguese University students (67 % female majoring in Social Sciences, Biological Sciences or Engineering and Exact Sciences. The content, construct and predictive validity, and reliability of the USEI were tested. The validated USEI was composed of 15 items, and supported the tri-factorial structure of student engagement. We documented evidence of adequate reliability, factorial, convergent and discriminant validities. USEI’s concurrent validity, with the Utrecht Work Engagement Scale-Student Survey, and the predictive validity for self-reported academic achievement and intention to dropout from school were also observed.

  19. Relationship quality and student engagement

    Science.gov (United States)

    Culver, Jennifer

    The purpose of this study was to examine the qualities of support, relatedness, and negative interaction within parent-child and teacher-student relationships and their association with cognitive, psychological, and behavioral engagement. Additionally, this study explored the contributions of cognitive and psychological engagement on behavioral engagement. The role of gender, grade, and ethnicity on relationship quality and engagement was also considered. Participants (n=311) were students in grades three through five from a suburban school district in southeastern Michigan. Perceptions of teacher-student relationship quality varied by grade level. In general, younger students reported greater teacher support and relatedness in comparison to older students. Conversely, older students perceived greater conflict within the teacher-student relationship. Student engagement also varied by grade level, with younger students reporting greater engagement than older students. Ethnicity also contributed to variance in student engagement, with African American students reporting significantly more engagement than Caucasian or Multiracial students. Teacher-student relationship quality was a significant predictor of student engagement, even after controlling for student characteristics and parent-child relationship variables. Results of path analysis revealed that cognitive and psychological engagement contributed significantly to behavioral engagement.

  20. Engagement as a Driver of Growth of Online Health Forums: Observational Study

    Science.gov (United States)

    Gopalsamy, Rahul; Semenov, Alexander; Pasiliao, Eduardo; McIntosh, Scott

    2017-01-01

    Background The emerging research on nurturing the growth of online communities posits that it is in part attributed to network effects, wherein every increase in the volume of user-generated content increases the value of the community in the eyes of its potential new members. The recently introduced metric engagement capacity offers a means of quantitatively assessing the ability of online platform users to engage each other into generating content; meanwhile, the quantity engagement value is useful for quantifying communication-based platform use. If the claim that higher engagement leads to accelerated growth holds true for online health forums (OHFs), then engagement tracking should become an important tool in the arsenal of OHF managers. Indeed, it might allow for quantifying the ability of an OHF to exploit network effects, thus predicting the OHF’s future success. Objective This study aimed to empirically analyze the relationship between internal OHF use (quantified using engagement measurement), and external growth. Methods We collected data from 7 OHFs posted between the years 1999 and 2016. Longitudinal analyses were conducted by evaluating engagement in the OHFs over time. We analyzed 2-way causality effects between the engagement value and metrics evaluating OHF growth using Granger causality tests. User activity metrics per week were correlated with engagement metrics, followed by linear regression analyses. Results Observational data showed a 1-way causal relationship between the OHF engagement value and reach (P=.02). We detected a 2-way causal relationship between the engagement value and delurking, with further analysis indicating that the engagement value was more likely to cause delurking (Pdepending on how much one user engaged another) to develop personal connections. Finally, we found that the more engaging an OHF user was in a given week, the more likely (up to 2 times, depending on their ability to engage others) they were to remain active

  1. Are mothers’ and fathers’ parenting characteristics associated with emerging adults’ academic engagement?

    Science.gov (United States)

    Waterman, Emily A.; Lefkowitz, Eva S.

    2017-01-01

    Although parenting is clearly linked to academic engagement in adolescence, less is known about links between parenting and academic engagement in emerging adulthood. A diverse sample of college students (N = 633; 53.1% female, 45.7% White/European American, 28.3% Asian American/Hawaiian/Pacific Islander, 26.4% Hispanic/Latino American, 21.6% Black/African American, and 2.8% Native American/American Indian) answered surveys about mothers’ and fathers’ parenting style, parent-offspring relationship quality, academic attitudes, academic behaviors, and academic performance. Emerging adults with more permissive mothers viewed grades as less important than emerging adults with less permissive mothers. Mothers’ authoritarian parenting, mothers’ permissive parenting, and relationship quality with father were differentially related to academic engagement depending on emerging adults’ gender. Both mothers’ and fathers’ parenting characteristics may impact the academic engagement of emerging adults via past parenting behaviors and current quality of the parent-offspring relationship, despite decreased physical proximity of emerging adults and their parents. PMID:28529398

  2. Are mothers' and fathers' parenting characteristics associated with emerging adults' academic engagement?

    Science.gov (United States)

    Waterman, Emily A; Lefkowitz, Eva S

    2017-06-01

    Although parenting is clearly linked to academic engagement in adolescence, less is known about links between parenting and academic engagement in emerging adulthood. A diverse sample of college students ( N = 633; 53.1% female, 45.7% White/European American, 28.3% Asian American/Hawaiian/Pacific Islander, 26.4% Hispanic/Latino American, 21.6% Black/African American, and 2.8% Native American/American Indian) answered surveys about mothers' and fathers' parenting style, parent-offspring relationship quality, academic attitudes, academic behaviors, and academic performance. Emerging adults with more permissive mothers viewed grades as less important than emerging adults with less permissive mothers. Mothers' authoritarian parenting, mothers' permissive parenting, and relationship quality with father were differentially related to academic engagement depending on emerging adults' gender. Both mothers' and fathers' parenting characteristics may impact the academic engagement of emerging adults via past parenting behaviors and current quality of the parent-offspring relationship, despite decreased physical proximity of emerging adults and their parents.

  3. Concentration and temperature dependence of short-range order in Ni-Ta solid solution using X-ray diffraction method

    International Nuclear Information System (INIS)

    Khwaja, F.A.; Alam, A.

    1980-09-01

    Diffuse X-ray scattering investigations about the existence of short-range order (SRO) have been carried out in the Ni-Ta system for different concentrations and annealing temperatures. It is observed that the values of the SRO parameters for the first co-ordination shell have anomalously large negative values for all the samples studied. These values of the α 1 depend upon the annealing temperatures and the concentration of Ta atoms in the Ni-Ta system. The results of the theoretical predictions of the ordering potential obtained using the formulae of the electronic theory of SRO, confirm the existence of very strong attractive correlation between the atoms of the different species in this system. (author)

  4. Depolarization-stimulated 42K+ efflux in rat aorta is calcium- and cellular volume-dependent

    International Nuclear Information System (INIS)

    Magliola, L.; Jones, A.W.

    1987-01-01

    The purpose of this study was to investigate the factors controlling membrane permeability to potassium of smooth muscle cells from rat aorta stimulated by depolarization. The increase 42 K+ efflux (change in the rate constant) induced by depolarization (application of high concentrations of potassium chloride) was inhibited significantly by the calcium antagonists diltiazem and nisoldipine. Parallel inhibitory effects on contraction were observed. Diltiazem also inhibited potassium-stimulated 36 Cl- efflux. The addition of 25-150 mM KCl to normal physiologic solution stimulated 42 K+ efflux in a concentration-dependent manner. Diltiazem suppressed potassium-stimulated 42 K+ efflux approximately 90% at 25 mM KCl and approximately 40% at 150 mM KCl. The ability of nisoldipine to inhibit 42 K+ efflux also diminished as the potassium chloride concentration was elevated. The component of efflux that was resistant to calcium antagonists probably resulted from a decrease in the electrochemical gradient for potassium. Cellular water did not change during potassium addition. Substitution of 80 and 150 mM KCl for sodium chloride produced cellular swelling and enhanced potassium-stimulated 42 K+ efflux compared with potassium chloride addition. The addition of sucrose to prevent cellular swelling reduced efflux response to potassium substitution toward that of potassium addition. A hypoosmolar physiologic solution produced an increase in the 42 K+ efflux and a contracture that were both prevented by the addition of sucrose. We concluded that the depolarization-mediated 42 K+ efflux has three components: one is calcium dependent; a second is dependent on cellular volume; and a third is resistant to inhibition by calcium antagonists

  5. Spatiotemporal Aspects of Engagement during Dialogic Storytelling Child–Robot Interaction

    Directory of Open Access Journals (Sweden)

    Scott Heath

    2017-06-01

    Full Text Available The success of robotic agents in close proximity of humans depends on their capacity to engage in social interactions and maintain these interactions over periods of time that are suitable for learning. A critical requirement is the ability to modify the behavior of the robot contingently to the attentional and social cues signaled by the human. A benchmark challenge for an engaging social robot is that of storytelling. In this paper, we present an exploratory study to investigate dialogic storytelling—storytelling with contingent responses—using a child-friendly robot. The aim of the study was to develop an engaging storytelling robot and to develop metrics for evaluating engagement. Ten children listened to an illustrated story told by a social robot during a science fair. The responses of the robot were adapted during the interaction based on the children’s engagement and touches of the pictures displayed by the robot on a tablet embedded in its torso. During the interaction the robot responded contingently to the child, but only when the robot invited the child to interact. We describe the robot architecture used to implement dialogic storytelling and evaluate the quality of human–robot interaction based on temporal (patterns of touch, touch duration and spatial (motions in the space surrounding the robot metrics. We introduce a novel visualization that emphasizes the temporal dynamics of the interaction and analyze the motions of the children in the space surrounding the robot. The study demonstrates that the interaction through invited contingent responses succeeded in engaging children, although the robot missed some opportunities for contingent interaction and the children had to adapt to the task. We conclude that (i the consideration of both temporal and spatial attributes is fundamental for establishing metrics to estimate levels of engagement in real-time, (ii metrics for engagement are sensitive to both the group and

  6. Engagement of the Rat Hindlimb Motor Cortex across Natural Locomotor Behaviors

    NARCIS (Netherlands)

    DiGiovanna, J.; Dominici, N.; Friedli, L.; Rigosa, J.; Duis, S.; Kreider, J.; Beauparlant, J.; van den Brand, R.; Schieppati, M.; Micera, S.; Courtine, G.

    2016-01-01

    Contrary to cats and primates, cortical contribution to hindlimb locomotor movements is not critical in rats. However, the importance of the motor cortex to regain locomotion after neurological disorders in rats suggests that cortical engagement in hindlimb motor control may depend on the behavioral

  7. Stress during Adolescence Alters Palatable Food Consumption in a Context-Dependent Manner.

    Science.gov (United States)

    Handy, Christine; Yanaga, Stephanie; Reiss, Avery; Zona, Nicole; Robinson, Emily; Saxton, Katherine B

    2016-01-01

    Food consumption and preferences may be shaped by exposure to stressful environments during sensitive periods in development, and even small changes in consumption can have important effects on long term health. Adolescence is increasingly recognized as a sensitive period, in which adverse experiences can alter development, but the specific programming effects that may occur during adolescence remain incompletely understood. The current study seeks to explore the effects of stress during late adolescence on consumption of a palatable, high-fat, high-sugar food in adulthood-under basal conditions, as well following acute stress. Male Long-Evans rats were exposed to a regimen of variable stress for seven days in late adolescence (PND 45-51). During the stress regimen, stressed animals gained significantly less weight than control animals, but weight in adulthood was unaffected by adolescent stress. Palatable food consumption differed between experimental groups, and the direction of effect depended on context; stressed rats ate significantly more palatable food than controls upon first exposure, but ate less following an acute stressor. Leptin levels and exploratory behaviors did not differ between stressed and non-stressed groups, suggesting that other factors regulate preference for a palatable food. Altered food consumption following adolescent stress suggests that rats remain sensitive to stress during late adolescence, and that adult feeding behavior may be affected by previous adverse experiences. Such programming effects highlight adolescence as a period of plasticity, with the potential to shape long term food consumption patterns and preferences.

  8. Defect chemistry modelling of oxygen-stoichiometry, vacancy concentrations, and conductivity of (La1-xSrx)(y)MnO3 +/-delta

    DEFF Research Database (Denmark)

    Poulsen, F.W.

    2000-01-01

    model, based on delocalised electrons, electron holes and all B-ions being trivalent is given in Appendix A. The sequential mathematical method allows us to calculate the high temperature oxygen partial pressure dependent properties of (La1-xSrx)(y)MnO3+/-delta in a unified manner irrespective...... are calculated by the small polaron model containing only ionic species - the B-ion may be Mn-B' (Mn2+), Mn-B(x) (Mn3+), and Mn-B(Mn4+). The A/B-ratio = y greatly influences the oxygen stoichiometry, oxygen ion vacancy- and cation vacancy concentrations and the total conductivity. Calculations are given...

  9. Take care of well-being: how facilitators and engagement predict performance of university students

    Directory of Open Access Journals (Sweden)

    Isabel M. Martínez

    2016-03-01

    Full Text Available The interest in developing a high quality educational system requires constant research of the variables involved in the teaching-learning process. Among these variables, social and academic facilitators are important because there is empirical evidence about their positive relationship with engagement, commitment, self-efficacy, happiness and satisfaction in the academic context. Moreover, the psychological well-being of university students (i.e., engagement showed to positively affect future academic success. In line, the aim of this study is twofold. First, the relevance of social and university academic facilitators was analyzed depending on the faculty of belonging. Second, the effect of social (e.g., Good relationship with classmates and academic facilitators (e.g., Updated website with new information and easily accessible as well as academic engagement on academic performance (i.e., GPA was tested. The sample consisted of 965 University students. The ANOVAs’ results showed the existence of statistically significant differences in social and university academic facilitators among the different faculties.  Regression analyses demonstrated that social (but not university’s facilitators and academic engagement were positively related to academic performance. Additionally, the interaction between social facilitators and academic engagement was positively related to academic performance.  The effect was also significant when controlling for gender and faculty. The identification of different facilitators allows to develop different activities depending on the faculty, as well as leading to the optimization of teaching-learning process. Moreover, academic facilitators do not affect academic performance. From a practical view, it means that specific interventions can be implemented during the course so that students’ social facilitators and engagement increase.

  10. Geophysicists' views about public engagement

    Science.gov (United States)

    Besley, J. C.; Dudo, A.; Yuan, S.

    2016-12-01

    The proposed talk would present the results of 2016 survey of American Geophysical Union members (n = 2040) about public engagement. This survey took place as part of a broader, NSF funded, study of engagement views across eight different U.S.-based scientific societies. The presentation would include data about geophysicists' past engagement behavior and willingness to engage alongside data about engagement attitudes, perceived norms (i.e. beliefs about whether peers engage and value engagement), and perceived efficacy (i.e., scientists' beliefs about their own communication skills and the impact of engagement). The presentation would also include results that describe scientists' overall goals for engagement (e.g., increasing support for specific policy positions, changing citizen behavior, etc.), as well as their communication-specific objectives (e.g., increasing knowledge, increase excitement, etc.). All of the results would be put in the context of equivalent results from scientists from seven other societies across a variety of fields, including chemistry, biology, and the social sciences. Three themes that would be emphasized in the presentation include (1) the fact that there are substantial commonalities in engagement views across scientific fields, (2) the important role that perceived engagement skill (efficacy) appears to play in predicting engagement willingness, and (3) a lack of evidence that scientists are thinking about engagement in strategic ways. Strategic engagement, in this regard, would involve setting clear goals and then choosing activities that the social science of science communication suggests might allow one to achieve those goals. The presentation would conclude with thoughts about what might be done to improve the effectiveness of science communication training.

  11. Resveratrol Exerts Dosage and Duration Dependent Effect on Human Mesenchymal Stem Cell Development

    Science.gov (United States)

    Peltz, Lindsay; Gomez, Jessica; Marquez, Maribel; Alencastro, Frances; Atashpanjeh, Negar; Quang, Tara; Bach, Thuy; Zhao, Yuanxiang

    2012-01-01

    Studies in the past have illuminated the potential benefit of resveratrol as an anticancer (pro-apoptosis) and life-extending (pro-survival) compound. However, these two different effects were observed at different concentration ranges. Studies of resveratrol in a wide range of concentrations on the same cell type are lacking, which is necessary to comprehend its diverse and sometimes contradictory cellular effects. In this study, we examined the effects of resveratrol on cell self-renewal and differentiation of human mesenchymal stem cells (hMSCs), a type of adult stem cells that reside in a number of tissues, at concentrations ranging from 0.1 to 10 µM after both short- and long-term exposure. Our results reveal that at 0.1 µM, resveratrol promotes cell self-renewal by inhibiting cellular senescence, whereas at 5 µM or above, resveratrol inhibits cell self-renewal by increasing senescence rate, cell doubling time and S-phase cell cycle arrest. At 1 µM, its effect on cell self-renewal is minimal but after long-term exposure it exerts an inhibitory effect, accompanied with increased senescence rate. At all concentrations, resveratrol promotes osteogenic differentiation in a dosage dependent manner, which is offset by its inhibitory effect on cell self-renewal at high concentrations. On the contrary, resveratrol suppresses adipogenic differentiation during short-term exposure but promotes this process after long-term exposure. Our study implicates that resveratrol is the most beneficial to stem cell development at 0.1 µM and caution should be taken in applying resveratrol as an anticancer therapeutic agent or nutraceutical supplement due to its dosage dependent effect on hMSCs. PMID:22615926

  12. Raman spectroscopic analysis of the carotenoid concentration in egg yolks depending on the feeding and housing conditions of the laying hens.

    Science.gov (United States)

    Hesterberg, Karoline; Schanzer, Sabine; Patzelt, Alexa; Sterry, Wolfram; Fluhr, Joachim W; Meinke, Martina C; Lademann, Jürgen; Darvin, Maxim E

    2012-01-01

    Resonance Raman spectroscopic measurements are suited to analyze the concentration of carotenoid antioxidants in biological samples. Previously, it has been shown that the carotenoid concentration of nutritional egg yolks has a direct influence on the carotenoid content of human skin in vivo. In the present study, resonance Raman spectroscopy was used to analyze the carotenoid concentration in the yolks of hen eggs, which were housed in battery cages or alternatively on free-range grassland. The egg yolks of hens, which had access to grassland, contained approximately double the amount of carotenoid concentration than the egg yolks of hens housed in battery cages (p egg yolks, depending on fodder, housing and weather conditions, were investigated. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Socially responsible investment engagement

    NARCIS (Netherlands)

    Goessling, T.; Buijter, Bas; Freeman, R.E.; Kujala, J.; Sachs, S.

    2017-01-01

    This study explores engagement in socially responsible investment (SRI) processes. More specifically, it researches the impact of shareholder salience on the success of engagement activities. The research question asks: What is the relationship between shareholder salience and engagement effort

  14. Stereotypes: A Preliminary Report on Mannerisms and Blindisms.

    Science.gov (United States)

    Leonhardt, M.

    1990-01-01

    The article describes current research on stereotypes in a group of blind children in Barcelona, Spain. Mannerisms and blindisms covering a range of verbal and motor behavior are defined and discussed, as are the variables of behavior related to them. (Author/DB)

  15. Does Self-Determination Predict the School Engagement of Four Different Motivation Types in Adolescence?

    Science.gov (United States)

    Raufelder, Diana; Regner, Nicola; Drury, Kate; Eid, Michael

    2016-01-01

    In order to enhance our understanding of inter-individual differences in scholastic motivation, this study examined if self-determination predicts the school engagement of four different motivation types (MT) in a large sample of adolescent students (N = 1088) from Brandenburg, Germany: (1) peer-dependent MT, (2) teacher-dependent MT, (3)…

  16. Concentration- and time-dependent genotoxicity profiles of isoprene monoepoxides and diepoxide, and the cross-linking potential of isoprene diepoxide in cells

    Directory of Open Access Journals (Sweden)

    Yan Li

    2014-01-01

    Full Text Available Isoprene, a possible carcinogen, is a petrochemical and a natural product being primarily produced by plants. It is biotransformed to 2-ethenyl-2-methyloxirane (IP-1,2-O and 2-(1-methylethenyloxirane (IP-3,4-O, both of which can be further metabolized to 2-methyl-2,2′-bioxirane (MBO. MBO is mutagenic, but IP-1,2-O and IP-3,4-O are not. While IP-1,2-O has been reported being genotoxic, the genotoxicity of IP-3,4-O and MBO, and the cross-linking potential of MBO have not been examined. In the present study, we used the comet assay to investigate the concentration- and time-dependent genotoxicity profiles of the three metabolites and the cross-linking potential of MBO in human hepatocyte L02 cells. For the incubation time of 1 h, all metabolites showed positive concentration-dependent profiles with a potency rank order of IP-3,4-O > MBO > IP-1,2-O. In human hepatocellular carcinoma (HepG2 and human leukemia (HL60 cells, IP-3,4-O was still more potent in inducing DNA breaks than MBO at high concentrations (>200 μM, although at low concentrations (≤200 μM IP-3,4-O exhibited slightly lower or similar potency to MBO. Interestingly, their time-dependent genotoxicity profiles (0.5–4 h in L02 cells were different from each other: IP-1,2-O and MBO (200 μM exhibited negative and positive profiles, respectively, with IP-3,4-O lying in between, namely, IP-3,4-O-caused DNA breaks did not change over the exposure time. Further experiments demonstrated that hydrolysis of IP-1,2-O contributed to the negative profile and MBO induced cross-links at high concentrations and long incubation times. Collectively, the results suggested that IP-3,4-O might play a significant role in the toxicity of isoprene.

  17. Erbium concentration dependent absorbance in tellurite glass

    Energy Technology Data Exchange (ETDEWEB)

    Sazali, E. S., E-mail: mdsupar@utm; Rohani, M. S., E-mail: mdsupar@utm; Sahar, M. R., E-mail: mdsupar@utm; Arifin, R., E-mail: mdsupar@utm; Ghoshal, S. K., E-mail: mdsupar@utm; Hamzah, K., E-mail: mdsupar@utm [Advanced Optical Material Research Group, Department of Physics, Faculty of Science, Universiti Teknologi Malaysia, 81310, Skudai, Johor Bahru, Johor (Malaysia)

    2014-09-25

    Enhancing the optical absorption cross-section in topically important rare earth doped tellurite glasses is challenging for photonic devices. Controlled synthesis and detailed characterizations of the optical properties of these glasses are important for the optimization. The influence of varying concentration of Er{sup 3+} ions on the absorbance characteristics of lead tellurite glasses synthesized via melt-quenching technique are investigated. The UV-Vis absorption spectra exhibits six prominent peaks centered at 490, 526, 652, 800, 982 and 1520 nm ascribed to the transitions in erbium ion from the ground state to the excited states {sup 4}F{sub 7/2}, {sup 2}H{sub 11/2}, {sup 4}F{sub 9/2}, {sup 4}I{sub 9/2}, {sup 2}H{sub 11/2} and {sup 4}I{sub 13/2}, respectively. The results are analyzed by means of optical band gap E{sub g} and Urbach energy E{sub u}. The values of the energy band gap are found decreased from 2.82 to 2.51 eV and the Urbach energy increased from 0.15 to 0.24 eV with the increase of the Er{sub 2}O{sub 3} concentration from 0 to 1.5 mol%. The excellent absorbance of the prepared tellurite glasses makes them suitable for fabricating solid state lasers.

  18. Administration of Inulin-Supplemented Gluten-Free Diet Modified Calcium Absorption and Caecal Microbiota in Rats in a Calcium-Dependent Manner

    Directory of Open Access Journals (Sweden)

    Urszula Krupa-Kozak

    2017-07-01

    Full Text Available In coeliac disease (CD, the risk of adverse calcium balance and reduced bone density is induced mainly by the disease, but also by a gluten-free diet (GFD, the only accepted CD therapy. Prebiotics through the beneficial impact on intestinal microbiota may stimulate calcium (Ca absorption. In the present study, we hypothesised that the dietary inulin in GFD would influence positively the intestinal microbiota, and by that will stimulate the absorption of calcium (Ca, especially in the conditions of Ca malnutrition. In a six-weeks nutritional experiment on growing a significant (p < 0.05 luminal acidification, decrease in ammonia concentration and stimulation of short chain fatty acids formation indicated inulin-mediated beneficial effects on the caecal microbiota. However, the effect of inulin on characteristics of intestinal microbiota and mineral utilization depended on the dietary Ca intake from GFDs. Inulin stimulated bifidobacteria, in particular B. animalis species, only if a recommended amount of Ca was provided. Most benefits to mineral utilization from inulin consumption were seen in rats fed Ca-restricted GFD where it increased the relative Ca absorption. Administration of inulin to a GFDs could be a promising dietary strategy for beneficial modulation of intestinal ecosystem and by that for the improvement the Ca absorption.

  19. Administration of Inulin-Supplemented Gluten-Free Diet Modified Calcium Absorption and Caecal Microbiota in Rats in a Calcium-Dependent Manner.

    Science.gov (United States)

    Krupa-Kozak, Urszula; Markiewicz, Lidia H; Lamparski, Grzegorz; Juśkiewicz, Jerzy

    2017-07-06

    In coeliac disease (CD), the risk of adverse calcium balance and reduced bone density is induced mainly by the disease, but also by a gluten-free diet (GFD), the only accepted CD therapy. Prebiotics through the beneficial impact on intestinal microbiota may stimulate calcium (Ca) absorption. In the present study, we hypothesised that the dietary inulin in GFD would influence positively the intestinal microbiota, and by that will stimulate the absorption of calcium (Ca), especially in the conditions of Ca malnutrition. In a six-weeks nutritional experiment on growing a significant ( p < 0.05) luminal acidification, decrease in ammonia concentration and stimulation of short chain fatty acids formation indicated inulin-mediated beneficial effects on the caecal microbiota. However, the effect of inulin on characteristics of intestinal microbiota and mineral utilization depended on the dietary Ca intake from GFDs. Inulin stimulated bifidobacteria, in particular B. animalis species, only if a recommended amount of Ca was provided. Most benefits to mineral utilization from inulin consumption were seen in rats fed Ca-restricted GFD where it increased the relative Ca absorption. Administration of inulin to a GFDs could be a promising dietary strategy for beneficial modulation of intestinal ecosystem and by that for the improvement the Ca absorption.

  20. 45 CFR 1621.4 - Complaints by clients about manner or quality of legal assistance.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Complaints by clients about manner or quality of...) LEGAL SERVICES CORPORATION CLIENT GRIEVANCE PROCEDURES § 1621.4 Complaints by clients about manner or... clients about the manner or quality of legal assistance that has been rendered by the recipient to the...

  1. Protective effects of estrogen against vascular calcification via estrogen receptor α-dependent growth arrest-specific gene 6 transactivation

    International Nuclear Information System (INIS)

    Nanao-Hamai, Michiko; Son, Bo-Kyung; Hashizume, Tsuyoshi; Ogawa, Sumito; Akishita, Masahiro

    2016-01-01

    Vascular calcification is one of the major complications of cardiovascular disease and is an independent risk factor for myocardial infarction and cardiac death. Postmenopausal women have a higher prevalence of vascular calcification compared with premenopausal women, suggesting protective effects of estrogen (E2). However, the underlying mechanisms of its beneficial effects remain unclear. In the present study, we examined the inhibitory effects of E2 on vascular smooth muscle cell (VSMC) calcification, and found that growth arrest-specific gene 6 (Gas6), a crucial molecule in vascular calcification, is transactivated by estrogen receptor α (ERα) in response to E2. In human aortic smooth muscle cells, physiological levels of E2 inhibited inorganic phosphate (Pi)-induced calcification in a concentration-dependent manner. This inhibitory effect was significantly abolished by MPP, an ERα-selective antagonist, and ERα siRNA, but not by PHTPP, an ERβ-selective antagonist, and ERβ siRNA, implicating an ERα-dependent action. Apoptosis, an essential process for Pi-induced VSMC calcification, was inhibited by E2 in a concentration-dependent manner and further, MPP abolished this inhibition. Mechanistically, E2 restored the inhibited expression of Gas6 and phospho-Akt in Pi-induced apoptosis through ERα. Furthermore, E2 significantly activated Gas6 transcription, and MPP abrogated this E2-dependent Gas6 transactivation. E2-BSA failed to activate Gas6 transcription and to inhibit Ca deposition in VSMC, suggesting beneficial actions of genomic signaling by E2/nuclear ERα. Taken together, these results indicate that E2 exerts inhibitory effects on VSMC apoptosis and calcification through ERα-mediated Gas6 transactivation. These findings indicate a potential therapeutic strategy for the prevention of vascular calcification, especially in postmenopausal women. - Highlights: • E2 inhibits Pi-induced calcification in vascular smooth muscles cells. • E2 inhibits Pi

  2. Serotonin inputs to the dorsal BNST modulate anxiety in a 5-HT1A receptor dependent manner

    Science.gov (United States)

    Garcia-Garcia, Alvaro L.; Canetta, Sarah; Stujenske, Joseph M.; Burghardt, Nesha S.; Ansorge, Mark S.; Dranovsky, Alex; Leonardo, E. David

    2017-01-01

    Serotonin (5-HT) neurons project from the raphe nuclei throughout the brain where they act to maintain homeostasis. Here, we study 5-HT inputs into the bed nucleus of the stria terminalis (BNST), a major subdivision of the extended amygdala that has been proposed to regulate responses to anxiogenic environments in humans and rodents. While the dorsal part of the BNST (dBNST) receives dense 5-HT innervation, whether and how 5-HT in the dBNST normally modulates anxiety remains unclear. Using optogenetics, we demonstrate that activation of 5-HT terminals in the dBNST reduces anxiety in a highly anxiogenic environment. Further analysis revealed that optogenetic inhibition of 5-HT inputs into the dBNST increases anxiety in a less anxiogenic environment. We found that 5-HT predominantly hyperpolarizes dBNST neurons, reducing their activity in a manner that can be blocked by a 5-HT1A antagonist. Finally, we demonstrate that activation of 5-HT1A receptors in the dBNST is necessary for the anxiolytic effect observed following optogenetic stimulation of 5-HT inputs into the dBNST. These data reveal that 5-HT release in the dBNST modulates anxiety-like behavior via 5-HT1A receptors under naturalistic conditions. PMID:28761080

  3. Internet Use and Its Impact on Engagement in Leisure Activities in China

    Science.gov (United States)

    Zhou, Ronggang; Fong, Patrick S. W.; Tan, Peking

    2014-01-01

    Introduction Internet use has become an increasingly common leisure time activity among Chinese citizens. The association between Internet use and engagement in leisure activities is especially unclear among China population. This study aims to investigate Internet usage and to determine whether active Internet use is a marker for low or high levels of leisure time activities. Methods/Principal Findings With the use of a face-to-face structured questionnaire interview, a total of 2,400 respondents who met all screening requirements were surveyed to answer the questions in eight major cities in China. 66.2% (n = 1,589) of all respondents were identified as Internet users. Of these Internet users, 30.0%, 24.1%, 26.4%, and 19.6% were clustered as “informative or instrumental users,” “entertainment users,” “communication users,” and “advanced users,” respectively. Regarding time spent on Internet use in leisure time, more than 96% reported going online in non-work situations, and 26.2% (n = 416) were classified as “heavy Internet users.” A logistic regression analysis revealed that there were significant differences in some leisure activities between non-Internet users and Internet users, with an observed one-unit increase in the leisure time dependence category increasing the probability of engaging in mental or social activities. In contrast, Internet users were less engaged in physical exercise-related activities. In addition, advanced Internet users were generally more active in leisure time activities than non-Internet users and other types of users. Conclusion/Significance Internet use is one of very common leisure activities in Chinese citizens, and age, gender, income, and education are the key factors affecting Internet access. According to different types of leisure activities, Internet usage has different impacts on leisure activity engagement. High Internet dependence has no significant negative influence on engagement in mental

  4. Internet use and its impact on engagement in leisure activities in China.

    Directory of Open Access Journals (Sweden)

    Ronggang Zhou

    Full Text Available INTRODUCTION: Internet use has become an increasingly common leisure time activity among Chinese citizens. The association between Internet use and engagement in leisure activities is especially unclear among China population. This study aims to investigate Internet usage and to determine whether active Internet use is a marker for low or high levels of leisure time activities. METHODS/PRINCIPAL FINDINGS: With the use of a face-to-face structured questionnaire interview, a total of 2,400 respondents who met all screening requirements were surveyed to answer the questions in eight major cities in China. 66.2% (n = 1,589 of all respondents were identified as Internet users. Of these Internet users, 30.0%, 24.1%, 26.4%, and 19.6% were clustered as "informative or instrumental users," "entertainment users," "communication users," and "advanced users," respectively. Regarding time spent on Internet use in leisure time, more than 96% reported going online in non-work situations, and 26.2% (n = 416 were classified as "heavy Internet users." A logistic regression analysis revealed that there were significant differences in some leisure activities between non-Internet users and Internet users, with an observed one-unit increase in the leisure time dependence category increasing the probability of engaging in mental or social activities. In contrast, Internet users were less engaged in physical exercise-related activities. In addition, advanced Internet users were generally more active in leisure time activities than non-Internet users and other types of users. CONCLUSION/SIGNIFICANCE: Internet use is one of very common leisure activities in Chinese citizens, and age, gender, income, and education are the key factors affecting Internet access. According to different types of leisure activities, Internet usage has different impacts on leisure activity engagement. High Internet dependence has no significant negative influence on engagement in mental or

  5. "Participatory Cli-Fi": Crowdsourcing Voicemails from the Future to Spark Engagement and Discern Perceptions of Climate Change

    Science.gov (United States)

    Stovall, G.; Eklund, K.; Redsecker, K.; Hernandez, T.; Pfirman, S. L.; Orlove, B. S.

    2016-12-01

    Communicating climate science alone is not enough to engage the public with climate change: the gap between the abstract science and its impact on their future lives is often too great. We constructed FutureCoast, a collaborative game, to use participatory storymaking as the art that bridges that gap. The FutureCoast game pretended the voicemail system of the future "had a leak in it" and invited people to call and leave voicemail messages that seem to have leaked from the future. These crowdsourced voicemails are short first-person stories that often create complex, visceral experiences of potential climate impacts in listeners. We transcribed and coded this audio for content and affect, finding both a wide array of anticipated climate futures and trends in public sentiment about climate related impacts. Our analysis found the public engages with climate change in both rational and emotional manners which should be considered when motivating them to action. This presentation highlights our methodology and assessment of innovative gameful engagement, and summarizes how the FutureCoast "participatory cli-fi" approach has been employed in community and classroom settings after the close of the active period of the game.

  6. eHealth promotion and social innovation with youth: using social and visual media to engage diverse communities.

    Science.gov (United States)

    Norman, Cameron D; Yip, Andrea L

    2012-01-01

    Social media and the multimedia networks that they support provide a platform for engaging youth and young adults across diverse contexts in a manner that supports different forms of creative expression. Drawing on more than 15 years of experience using eHealth promotion strategies to youth engagement, the Youth Voices Research Group (YVRG) and its partners have created novel opportunities for young people to explore health topics ranging from tobacco use, food security, mental health, to navigation of health services. Through applying systems and design thinking, the YVRG approach to engaging youth will be presented using examples from its research and practice that combine social organizing with arts-informed methods for creative expression using information technology. This presentation focuses on the way in which the YVRG has introduced interactive blogging, photographic elicitation, and video documentaries, alongside real-world social action projects, to promote youth health and to assist in research and evaluation. Opportunities and barriers including literacy and access to technology are discussed and presented along with emerging areas of research including more effective use of smartphones and social networking platforms such as Twitter, Facebook, and YouTube in health promotion and public health.

  7. 26 CFR 1.871-1 - Classification and manner of taxing alien individuals.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 9 2010-04-01 2010-04-01 false Classification and manner of taxing alien... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Nonresident Aliens and Foreign Corporations § 1.871-1 Classification and manner of taxing alien individuals. (a) Classes of aliens. For purposes of the income tax...

  8. Age-dependent changes in the total protein concentrations in the ...

    African Journals Online (AJOL)

    related changes in total protein concentrations in ten regions of the pig brain and hypophyses from birth to 36 months of age. Age-related changes in protein concentrations in all the brain regions except the pons and cerebral cortex were not ...

  9. 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

  10. PERARES: Public Engagement with Research and Research Engagement with Society

    NARCIS (Netherlands)

    Steinhaus, Norbert; Mulder, Henk A.J.

    2014-01-01

    PERARES is a four-year project funded by the European Community's Seventh Framework Programme which started in 2010. The acronym stands for "Public Engagement with Research and Research Engagement with Society”. The project brings together Science Shops, Civil Society Organisations (CSOs) and

  11. Linking job demands and resources to employee engagement and burnout: a theoretical extension and meta-analytic test.

    Science.gov (United States)

    Crawford, Eean R; Lepine, Jeffery A; Rich, Bruce Louis

    2010-09-01

    We refine and extend the job demands-resources model with theory regarding appraisal of stressors to account for inconsistencies in relationships between demands and engagement, and we test the revised theory using meta-analytic structural modeling. Results indicate support for the refined and updated theory. First, demands and burnout were positively associated, whereas resources and burnout were negatively associated. Second, whereas relationships among resources and engagement were consistently positive, relationships among demands and engagement were highly dependent on the nature of the demand. Demands that employees tend to appraise as hindrances were negatively associated with engagement, and demands that employees tend to appraise as challenges were positively associated with engagement. Implications for future research are discussed. Copyright 2010 APA, all rights reserved

  12. Students Engaged in Learning

    Science.gov (United States)

    Ismail, Emad A.; Groccia, James E.

    2018-01-01

    Engaging students in learning is a basic principle of effective undergraduate education. Outcomes of engaging students include meaningful learning experiences and enhanced skills in all learning domains. This chapter reviews the influence of engaging students in different forms of active learning on cognitive, psychomotor, and affective skill…

  13. 18 CFR 344.2 - Manner of submitting quotations.

    Science.gov (United States)

    2010-04-01

    ... quotations. 344.2 Section 344.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE INTERSTATE COMMERCE ACT FILING QUOTATIONS FOR U.S. GOVERNMENT SHIPMENTS AT REDUCED RATES § 344.2 Manner of submitting quotations. (a) The quotation or tender...

  14. [Computer modeling the dependences of the membrane potential for polymeric membrane separated non-homogeneous electrolyte solutions on concentration Rayleigh number].

    Science.gov (United States)

    Slezak, Izabella H; Jasik-Slezak, Jolanta; Bilewicz-Wyrozumska, Teresa; Slezak, Andrzej

    2006-01-01

    On the basis of model equation describing the membrane potential delta psi(s) on concentration Rayleigh number (R(C)), mechanical pressure difference (deltaP), concentration polarization coefficient (zeta s) and ratio concentration of solutions separated by membrane (Ch/Cl), the characteristics delta psi(s) = f(Rc)(delta P, zeta s, Ch/Cl) for steady values of zeta s, R(C) and Ch/Cl in single-membrane system were calculated. In this system neutral and isotropic polymeric membrane oriented in horizontal plane, the non-homogeneous binary electrolytic solutions of various concentrations were separated. Nonhomogeneity of solutions is results from creations of the concentration boundary layers on both sides of the membrane. Calculations were made for the case where on a one side of the membrane aqueous solution of NaCl at steady concentration 10(-3) mol x l(-1) (Cl) was placed and on the other aqueous solutions of NaCl at concentrations from 10(-3) mol x l(-1) to 2 x 10(-2) mol x l(-1) (Ch). Their densities were greater than NaCl solution's at 10(-3) mol x l(-1). It was shown that membrane potential depends on hydrodynamic state of a complex concentration boundary layer-membrane-concentration boundary layer, what is controlled by deltaP, Ch/Cl, Rc and Zeta(s).

  15. Pragmatic awareness of Suggestions: From (Im)Polite Mannerism to Attitudinal Appropriateness

    OpenAIRE

    Hamid Allami; Nasim Boustani

    2017-01-01

    The present research seeks to determine: (a) Iranian EFL learners’ application of suggestion semantic formulae ;(b) their attitude of appropriateness in terms of confidence in the employment of appropriate supportive moves; (c), their (im)polite mannerism with respect to the selected strategies; and (d) the relationship between attitude of appropriateness and mannerism of (im)politeness. An Oxford Quick placement Test (OQPT) was administered among 60 Iranian EFL learners to check their langua...

  16. A Study of Engagement in Active and Passive Roles in Casual Leisure Occupations

    Directory of Open Access Journals (Sweden)

    Anne M. Fenech

    2015-04-01

    Full Text Available Background: This article explores whether engagement with listening occupations varies depending on the occupational role or the level of sensory stimulation presented to participants with neuropalliative conditions. Method: The study used a multiple case quasi-experimental study involving marginal-participant timesampled observations of engagement of individuals with neuropalliative conditions, with casual leisure occupations using the Individual Child Engagement Record. Data was collected using the Individual Child Engagement Record with 14 participants (who had Barthel scores averaging 7/100. The participants represented a particular sub-group of individuals with profound levels of neurological disability. Results: The time-sampled observations of engagement showed a significant difference between the scores for the control condition, engagement in a potentially active role at a music-making group, and engagement in a passive audience role when listening to an audio recording. Therefore, passively listening to an audio recording appears to be less engaging than the potentially active role offered by the music-making group for participants with neuropalliative conditions. Conclusion: The small sample size and the use of a single observer without video recording backup compromised the reliability of the data while complying with the facility’s POVA policy. Switching on an auditory recording or broadcast, while easy to arrange, may not be sufficiently engaging to prevent boredom and occupational deprivation. Consideration of an individual’s sensory, support, and role preference should be undertaken when designing leisure occupations for individuals with neuropalliative conditions rather than simply switching on an audio recording or broadcast

  17. Care mapping in clinical neuroscience settings: Cognitive impairment and dependency.

    Science.gov (United States)

    Leigh, Andrew James; O'Hanlon, Katie; Sheldrick, Russell; Surr, Claire; Hare, Dougal Julian

    2015-01-01

    Person-centred care can improve the well-being of patients and is therefore a key driver in healthcare developments in the UK. The current study aims to investigate the complex relationship between cognitive impairment, dependency and well-being in people with a wide range of acquired brain and spinal injuries. Sixty-five participants, with varied acquired brain and spinal injuries, were selected by convenience sampling from six inpatient clinical neuroscience settings. Participants were observed using Dementia Care Mapping - Neurorehabilitation (DCM-NR) and categorised based on severity of cognitive impairment. A significant difference in the behaviours participants engaged in, their well-being and dependency was found between the severe cognitive impairment group and the mild, moderate or no cognitive impairment groups. Dependency and cognitive impairment accounted for 23.9% of the variance in well-ill-being scores and 17.2% of the variance in potential for positive engagement. The current study highlights the impact of severe cognitive impairment and dependency on the behaviours patients engaged in and their well-being. It also affirms the utility of DCM-NR in providing insights into patient experience. Consideration is given to developing DCM-NR as a process that may improve person-centred care in neuroscience settings.

  18. Student Engagement in Assessments: What Students and Teachers Find Engaging

    Science.gov (United States)

    Bae, Soung; Kokka, Kari

    2016-01-01

    Although research has shown that student engagement is strongly related to performance on assessment tasks, especially for traditionally underserved subgroups of students, increasing student engagement has not been the goal of standardized tests of content knowledge. Recent state and federal policies, however, are changing the assessment…

  19. Health Risk Information Engagement and Amplification on Social Media.

    Science.gov (United States)

    Strekalova, Yulia A

    2017-04-01

    Emerging pandemics call for unique health communication and education strategies in which public health agencies need to satisfy the public's information needs about possible risks while preventing risk exaggeration and dramatization. As a route to providing a framework for understanding public information behaviors in response to an emerging pandemic, this study examined the characteristics of communicative behaviors of social media audiences in response to Ebola outbreak news. Grounded in the social amplification of risks framework, this study adds to an understanding of information behaviors of online audiences by showing empirical differences in audience engagement with online health information. The data were collected from the Centers for Disease Control and Prevention (CDC) Facebook channel. The final data set included 809 CDC posts and 35,916 audience comments. The analysis identified the differences in audience information behaviors in response to an emerging pandemic, Ebola, and health promotion posts. While the CDC had fewer posts on Ebola than health promotion topics, the former received more attention from active page users. Furthermore, audience members who actively engaged with Ebola news had a small overlap with those who engaged with non-Ebola information during the same period. Overall, this study demonstrated that information behavior and audience engagement is topic dependent. Furthermore, audiences who commented on news about an emerging pandemic were homogenous and varied in their degree of information amplification.

  20. Evidence that two ATP-dependent (Lon proteases in Borrelia burgdorferi serve different functions.

    Directory of Open Access Journals (Sweden)

    James L Coleman

    2009-11-01

    Full Text Available The canonical ATP-dependent protease Lon participates in an assortment of biological processes in bacteria, including the catalysis of damaged or senescent proteins and short-lived regulatory proteins. Borrelia spirochetes are unusual in that they code for two putative ATP-dependent Lon homologs, Lon-1 and Lon-2. Borrelia burgdorferi, the etiologic agent of Lyme disease, is transmitted through the blood feeding of Ixodes ticks. Previous work in our laboratory reported that B. burgdorferi lon-1 is upregulated transcriptionally by exposure to blood in vitro, while lon-2 is not. Because blood induction of Lon-1 may be of importance in the regulation of virulence factors critical for spirochete transmission, the clarification of functional roles for these two proteases in B. burgdorferi was the object of this study. On the chromosome, lon-2 is immediately downstream of ATP-dependent proteases clpP and clpX, an arrangement identical to that of lon of Escherichia coli. Phylogenetic analysis revealed that Lon-1 and Lon-2 cluster separately due to differences in the NH(2-terminal substrate binding domains that may reflect differences in substrate specificity. Recombinant Lon-1 manifested properties of an ATP-dependent chaperone-protease in vitro but did not complement an E. coli Lon mutant, while Lon-2 corrected two characteristic Lon-mutant phenotypes. We conclude that B. burgdorferi Lons -1 and -2 have distinct functional roles. Lon-2 functions in a manner consistent with canonical Lon, engaged in cellular homeostasis. Lon-1, by virtue of its blood induction, and as a unique feature of the Borreliae, may be important in host adaptation from the arthropod to a warm-blooded host.

  1. Experiments in engagement: Designing public engagement with science and technology for capacity building.

    Science.gov (United States)

    Selin, Cynthia; Rawlings, Kelly Campbell; de Ridder-Vignone, Kathryn; Sadowski, Jathan; Altamirano Allende, Carlo; Gano, Gretchen; Davies, Sarah R; Guston, David H

    2017-08-01

    Public engagement with science and technology is now widely used in science policy and communication. Touted as a means of enhancing democratic discussion of science and technology, analysis of public engagement with science and technology has shown that it is often weakly tied to scientific governance. In this article, we suggest that the notion of capacity building might be a way of reframing the democratic potential of public engagement with science and technology activities. Drawing on literatures from public policy and administration, we outline how public engagement with science and technology might build citizen capacity, before using the notion of capacity building to develop five principles for the design of public engagement with science and technology. We demonstrate the use of these principles through a discussion of the development and realization of the pilot for a large-scale public engagement with science and technology activity, the Futurescape City Tours, which was carried out in Arizona in 2012.

  2. Low concentrations of salicylic acid delay methyl jasmonate-induced leaf senescence by up-regulating nitric oxide synthase activity.

    Science.gov (United States)

    Ji, Yingbin; Liu, Jian; Xing, Da

    2016-09-01

    In plants, extensive efforts have been devoted to understanding the crosstalk between salicylic acid (SA) and jasmonic acid (JA) signaling in pathogen defenses, but this crosstalk has scarcely been addressed during senescence. In this study, the effect of SA application on methyl jasmonate (MeJA)-induced leaf senescence was assessed. We found that low concentrations of SA (1-50 μM) played a delayed role against the senescence promoted by MeJA. Furthermore, low concentrations of SA enhanced plant antioxidant defenses and restricted reactive oxygen species (ROS) accumulation in MeJA-treated leaves. When applied simultaneously with MeJA, low concentrations of SA triggered a nitric oxide (NO) burst, and the elevated NO levels were linked to the nitric oxide associated 1 (NOA1)-dependent pathway via nitric oxide synthase (NOS) activity. The ability of SA to up-regulate plant antioxidant defenses, reduce ROS accumulation, and suppress leaf senescence was lost in NO-deficient Atnoa1 plants. In a converse manner, exogenous addition of NO donors increased the plant antioxidant capacity and lowered the ROS levels in MeJA-treated leaves. Taken together, the results indicate that SA at low concentrations counteracts MeJA-induced leaf senescence through NOA1-dependent NO signaling and strengthening of the antioxidant defense. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  3. "Know your audience": A hospital community engagement programme in a non-profit paediatric hospital in Cambodia.

    Directory of Open Access Journals (Sweden)

    Sreymom Pol

    Full Text Available The purpose of this evaluation is to explore the impact of the new hospital community engagement programme (comprised of a Young Persons Advisory Group and a Science Café on community members and other stakeholders, with regard to their attitudes, skills and degree of engagement in a paediatric hospital in Cambodia.Data collection included feedback questionnaires and reflections produced after each YPAG and Science Café event. Further questionnaires and reflective interviews were conducted to gather the views of key stakeholders. Data were analysed by thematic content analysis and numerical data were expressed using descriptive statistics.The vast majority of participants expressed their enjoyment and satisfaction of the hospital community engagement programme. Delivering the programme in the right manner for the target audiences, by prioritising their needs was key to this. Participants valued the programmes in terms of the knowledge delivered around good health practices, the skills developed such as confidence and responsibility for their health, and the provision of opportunities to voice their opinions. All stakeholders recognised the importance of the programme in improving the quality of the healthcare service provided at the hospital.In order to have a successful hospital community engagement programme, understanding the target audience is essential. The engagement programme must be delivered in the right way to meet the needs of community members, including right communication, right setting, right people and right timing. This will ultimately result in a meaningful programme that is able to empower community members, potentially resulting in lasting change in healthcare practices. In conclusion, the gap between hospitals and the community could narrow, allowing everyone to interact and learn from each other.

  4. Transnational television audiences and modes of engagement: studying audience engagement as a set of experiences

    DEFF Research Database (Denmark)

    Keinonen, Heidi; Jensen, Pia Majbritt; Esser, Andrea

    2018-01-01

    Audience engagement is attracting increasing attention in various academic disciplines. Recently, the industry- and technology-oriented conceptualizations of engagement have been challenged by a more audience-oriented understanding. This article aims at contributing to the development of a more...... nuanced audience-oriented approach. First, we make a theoretical argument by bringing various key theories together and, second, we present an empirical contribution by analysing audience engagement as a set of experiences. Our analysis builds on the empirical material produced by conducting two rounds...... and ritualistic engagement, ludic engagement. We also discovered that audiences at times get disengaged or opt to actively resist engagement....

  5. Neurotrophin release by neurotrophins: Implications for activity-dependent neuronal plasticity

    OpenAIRE

    Canossa, Marco; Griesbeck, Oliver; Berninger, Benedikt; Campana, Gabriele; Kolbeck, Roland; Thoenen, Hans

    1997-01-01

    Neurotrophins, secreted in an activity-dependent manner, are thought to be involved in the activity-dependent refinement of synaptic connections. Here we demonstrate that in hippocampal neurons and the rat pheochromocytoma cell line PC12 application of exogenous neurotrophins induces secretion of neurotrophins, an effect that is mediated by the activation of tyrosine kinase neurotrophin receptors (Trks). Like activity-dependent secretion of neurotrophins, neurotrophin-induced neurotrophin sec...

  6. Measuring patient engagement: development and psychometric properties of the Patient Health Engagement (PHE) Scale.

    Science.gov (United States)

    Graffigna, Guendalina; Barello, Serena; Bonanomi, Andrea; Lozza, Edoardo

    2015-01-01

    Beyond the rhetorical call for increasing patients' engagement, policy makers recognize the urgency to have an evidence-based measure of patients' engagement and capture its effect when planning and implementing initiatives aimed at sustaining the engagement of consumers in their health. In this paper, authors describe the Patient Health Engagement Scale (PHE-scale), a measure of patient engagement that is grounded in rigorous conceptualization and appropriate psychometric methods. The scale was developed based on our previous conceptualization of patient engagement (the PHE-model). In particular, the items of the PHE-scale were developed based on the findings from the literature review and from interviews with chronic patients. Initial psychometric analysis was performed to pilot test a preliminary version of the items. The items were then refined and administered to a national sample of chronic patients (N = 382) to assess the measure's psychometric performance. A final phase of test-retest reliability was performed. The analysis showed that the PHE Scale has good psychometric properties with good correlation with concurrent measures and solid reliability. Having a valid and reliable measure to assess patient engagement is the first step in understanding patient engagement and its role in health care quality, outcomes, and cost containment. The PHE Scale shows a promising clinical relevance, indicating that it can be used to tailor intervention and assess changes after patient engagement interventions.

  7. Measuring Student Engagement in the Online Course: The Online Student Engagement Scale (OSE)

    Science.gov (United States)

    Dixson, Marcia D.

    2015-01-01

    Student engagement is critical to student learning, especially in the online environment, where students can often feel isolated and disconnected. Therefore, teachers and researchers need to be able to measure student engagement. This study provides validation of the Online Student Engagement scale (OSE) by correlating student self-reports of…

  8. Constituting Public Engagement

    DEFF Research Database (Denmark)

    Davies, Sarah Rachael

    2013-01-01

    understanding of science to those of public engagement with science and technology (PEST), and the histories, or genealogies, of such models. Data from two qualitative studies-a case study of one of the United Kingdom'ssix Beacons for Public Engagement and a study of contract research staff-are used......This article uses data from two U.K. studies in order to explore the meanings attached to public engagement. It focuses on two issues of importance to contemporary discussions of science communication: the degree to which there has been a smooth transition, in practice, from models of public...... to characterize the ways in which U.K. academic communities understand PEST. It is argued that engagement is construed as multiple, relational, and outcomes oriented, with seven key outcomes ranging from better research to empowered individuals. These differences are traced to personal and professional...

  9. Engaging patients to recover life projectuality: an Italian cross-disease framework.

    Science.gov (United States)

    Barello, Serena; Graffigna, Guendalina

    2015-05-01

    Chronic disease is recognized as having a large impact on patient quality of life (QoL), which can be defined as an individual's satisfaction or happiness with life in domains he or she considers important. Policy makers and clinicians recognize increasingly that patients can safeguard their QoL by making healthy lifestyle choices and being actively engaged in their health care. However, in the emphasis on promoting patient engagement to enhance patients' QoL, there is no consensus regarding the relationship between QOL and patient engagement, resulting in a lack of shared guidelines among clinicians on interventions. Furthermore, no studies have provided an in-depth exploration of the perspective of patients with chronic conditions who are engaged in their health care and their requirements to achieve an improved QoL. Given this theoretical gap, the present study attempted to explore the patient engagement experience and its relationship with patient QoL in the context of the Italian healthcare system and in relation to different chronic diseases. In-depth qualitative interviews on a sample of 99 patients with a wide variety of chronic conditions (heart failure, chronic obstructive pulmonary disease, stroke, diabetes, and cancer). Patient engagement in health care can be defined as a context-based and cross-disease process that appears to enable patients to recover their life projectuality, which had been impaired by the onset of chronic disease. Successful patient engagement may also be related to a positive shift in the ways in which patients perceive self and life and experience empowerment to realize their life potential, thus improving quality of life. Patient engagement is a powerful concept capable of reflecting significant psychosocial changes that promote patient QoL along the care process. There appears to be theoretical and empirical justification for a broad definition of QoL. QoL deeply depends on the patient ability to engage in their care and on the

  10. Work Demands-Burnout and Job Engagement-Job Satisfaction Relationships: Teamwork as a Mediator and Moderator.

    Science.gov (United States)

    Mijakoski, Dragan; Karadzinska-Bislimovska, Jovanka; Basarovska, Vera; Minov, Jordan; Stoleski, Sasho; Angeleska, Nada; Atanasovska, Aneta

    2015-03-15

    Few studies have examined teamwork as mediator and moderator of work demands-burnout and job engagement-job satisfaction relationships in healthcare workers (HCWs) in South-East Europe. To assess mediation and moderation effect of teamwork on the relationship between independent (work demands or job engagement) and dependent (burnout or job satisfaction) variables. Work demands, burnout, job engagement, and job satisfaction were measured with Hospital Experience Scale, Maslach Burnout Inventory, Utrecht Work Engagement Scale, and Job Satisfaction Survey, respectively. Hospital Survey on Patient Safety Culture was used for assessment of teamwork. In order to examine role of teamwork as a mediating variable we fit series of regression models for burnout and job satisfaction. We also fit regression models predicting outcome (burnout or job satisfaction) from predictor (work demands or job engagement) and moderator (teamwork) variable. Teamwork was partial mediator of work demands-burnout relationship and full mediator of job engagement-job satisfaction relationship. We found that only job engagement-job satisfaction relationship was moderated by teamwork. Occupational health services should target detection of burnout in HCWs and implementation of organizational interventions in hospitals, taking into account findings that teamwork predicted reduced burnout and higher job satisfaction.

  11. Globalized conflicts, globalized responses. Changing manners of contestation among indigenous communities

    DEFF Research Database (Denmark)

    Benyei, Petra; Turreira Garcia, Nerea; Orta-Martínez, Martí

    2017-01-01

    In a globalized world, environmental conflicts affecting indigenous communities (including hunter-gatherer groups) have intensified and grown in their transnational character. These changes have affected the choice of manners of contestation of these groups, favouring in some cases the emergence...... activities and confront conflicts through a truly bottom-up approach. The chapter ends discussing how, despite the potential of such new manners of contestation, the power imbalances that currently underpin many indigenous conflicts are first to be addressed....

  12. 26 CFR 301.6316-5 - Manner of paying tax by foreign currency.

    Science.gov (United States)

    2010-04-01

    ... currency to be deposited shall be that amount which, when converted at the rate of exchange used on the... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Manner of paying tax by foreign currency. 301....6316-5 Manner of paying tax by foreign currency. (a) Time and place to pay. The unpaid tax required to...

  13. Measuring user engagement

    CERN Document Server

    Lalmas, Mounia; Yom-Tov, Elad

    2014-01-01

    User engagement refers to the quality of the user experience that emphasizes the positive aspects of interacting with an online application and, in particular, the desire to use that application longer and repeatedly. User engagement is a key concept in the design of online applications (whether for desktop, tablet or mobile), motivated by the observation that successful applications are not just used, but are engaged with. Users invest time, attention, and emotion in their use of technology, and seek to satisfy pragmatic and hedonic needs. Measurement is critical for evaluating whether online

  14. Coronavirus cell entry occurs through the endo-/lysosomal pathway in a proteolysis-dependent manner.

    Directory of Open Access Journals (Sweden)

    Christine Burkard

    2014-11-01

    Full Text Available Enveloped viruses need to fuse with a host cell membrane in order to deliver their genome into the host cell. While some viruses fuse with the plasma membrane, many viruses are endocytosed prior to fusion. Specific cues in the endosomal microenvironment induce conformational changes in the viral fusion proteins leading to viral and host membrane fusion. In the present study we investigated the entry of coronaviruses (CoVs. Using siRNA gene silencing, we found that proteins known to be important for late endosomal maturation and endosome-lysosome fusion profoundly promote infection of cells with mouse hepatitis coronavirus (MHV. Using recombinant MHVs expressing reporter genes as well as a novel, replication-independent fusion assay we confirmed the importance of clathrin-mediated endocytosis and demonstrated that trafficking of MHV to lysosomes is required for fusion and productive entry to occur. Nevertheless, MHV was shown to be less sensitive to perturbation of endosomal pH than vesicular stomatitis virus and influenza A virus, which fuse in early and late endosomes, respectively. Our results indicate that entry of MHV depends on proteolytic processing of its fusion protein S by lysosomal proteases. Fusion of MHV was severely inhibited by a pan-lysosomal protease inhibitor, while trafficking of MHV to lysosomes and processing by lysosomal proteases was no longer required when a furin cleavage site was introduced in the S protein immediately upstream of the fusion peptide. Also entry of feline CoV was shown to depend on trafficking to lysosomes and processing by lysosomal proteases. In contrast, MERS-CoV, which contains a minimal furin cleavage site just upstream of the fusion peptide, was negatively affected by inhibition of furin, but not of lysosomal proteases. We conclude that a proteolytic cleavage site in the CoV S protein directly upstream of the fusion peptide is an essential determinant of the intracellular site of fusion.

  15. Engagement and Empathy Discourses in Corporate Communication: The Case of “The Science of Engagement”

    Directory of Open Access Journals (Sweden)

    Liz Yeomans

    2015-12-01

    Full Text Available This paper analyzes engagement and empathy discourse in a corporate document The Science of Engagement published online by a leading UK PR agency. The method used was a critical discourse analysis (CDA of the document, and the findings reveal that the engagement discourse in this document positions the consumer as a passive, compulsive purchaser, while the empathy discourse largely frames the consumer as young and more empathic than previous generations, and thus an easily accessible target for brands to appeal to, using emotional communication on social media. The conclusion of the paper is that in contrast to conceptual understandings of engagement as two-way and empathy as other-oriented, the Agency relies on early understanding of engagement as a cognitive process based on instincts and persuasive communication, and not as a concept of social communication that will be dependent on cultural and social differences, individual approach, and trust. This practice goes against the already acknowledged view of engagement and empathy as more than just cognitive responses by consumers, and presents an outdated understanding of these increasingly debated concepts.

  16. Nicotine Dependence, Physical Activity, and Sedentary Behavior among Adult Smokers.

    Science.gov (United States)

    Loprinzi, Paul D; Walker, Jerome F

    2015-03-01

    Research has previously demonstrated an inverse association between smoking status and physical activity; however, few studies have examined the association between nicotine dependence and physical activity or sedentary behavior. This study examined the association between nicotine dependence and accelerometer-determined physical activity and sedentary behavior. Data from the 2003-2006 National Health and Nutrition Examination Survey (NHANES) were used. A total of 851 adult (≥20 years) smokers wore an accelerometer for ≥4 days and completed the Fagerstrom Test for Nicotine Dependence scale. Regression models were used to examine the association between nicotine dependence and physical activity/sedentary behavior. After adjusting for age, gender, race-ethnicity, poverty level, hypertension, emphysema, bronchitis, body mass index (BMI), cotinine, and accelerometer wear time, smokers 50 + years of age with greater nicotine dependence engaged in more sedentary behavior (β = 11.4, P = 0.02) and less light-intensity physical activity (β = -9.6, P = 0.03) and moderate-to-vigorous physical activity (MVPA; β = -0.14, P = 0.003) than their less nicotine dependent counterparts. Older adults who are more nicotine dependent engage in less physical activity (both MVPA and light-intensity) and more sedentary behavior than their less nicotine dependent counterparts.

  17. The ASTUTE Health study protocol: deliberative stakeholder engagements to inform implementation approaches to healthcare disinvestment.

    Science.gov (United States)

    Watt, Amber M; Hiller, Janet E; Braunack-Mayer, Annette J; Moss, John R; Buchan, Heather; Wale, Janet; Riitano, Dagmara E; Hodgetts, Katherine; Street, Jackie M; Elshaug, Adam G

    2012-10-22

    Governments and other payers are yet to determine optimal processes by which to review the safety, effectiveness, and cost-effectiveness of technologies and procedures that are in active use within health systems, and rescind funding (partially or fully) from those that display poor profiles against these parameters. To further progress a disinvestment agenda, a model is required to support payers in implementing disinvestment in a transparent manner that may withstand challenge from vested interests and concerned citizens. Combining approaches from health technology assessment and deliberative democratic theory, this project seeks to determine if and how wide stakeholder engagement can contribute to improved decision-making processes, wherein the views of both vested and non-vested stakeholders are seen to contribute to informing policy implementation within a disinvestment context. Systematic reviews pertaining to illustrative case studies were developed and formed the evidence base for discussion. Review findings were presented at a series of deliberative, evidence-informed stakeholder engagements, including partisan (clinicians and consumers) and non-partisan (representative community members) stakeholders. Participants were actively facilitated towards identifying shared and dissenting perspectives regarding public funding policy for each of the case studies and developing their own funding models in response to the evidence presented. Policy advisors will subsequently be invited to evaluate disinvestment options based on the scientific and colloquial evidence presented to them, and to explore the value of this information to their decision-making processes with reference to disinvestment. Analysis of the varied outputs of the deliberative engagements will contribute to the methodological development around how to best integrate scientific and colloquial evidence for consideration by policy advisors. It may contribute to the legitimization of broad and

  18. Brassinolide Increases Potato Root Growth In Vitro in a Dose-Dependent Way and Alleviates Salinity Stress

    Directory of Open Access Journals (Sweden)

    Yueqing Hu

    2016-01-01

    Full Text Available Brassinosteroids (BRs are steroidal phytohormones that regulate various physiological processes, such as root development and stress tolerance. In the present study, we showed that brassinolide (BL affects potato root in vitro growth in a dose-dependent manner. Low BL concentrations (0.1 and 0.01 μg/L promoted root elongation and lateral root development, whereas high BL concentrations (1–100 μg/L inhibited root elongation. There was a significant (P<0.05 positive correlation between root activity and BL concentrations within a range from 0.01 to 100 μg/L, with the peak activity of 8.238 mg TTC·g−1 FW·h−1 at a BL concentration of 100 μg/L. Furthermore, plants treated with 50 μg/L BL showed enhanced salt stress tolerance through in vitro growth. Under this scenario, BL treatment enhanced the proline content and antioxidant enzymes’ (superoxide dismutase, peroxidase, and catalase activity and reduced malondialdehyde content in potato shoots. Application of BL maintain K+ and Na+ homeostasis by improving tissue K+/Na+ ratio. Therefore, we suggested that the effects of BL on root development from stem fragments explants as well as on primary root development are dose-dependent and that BL application alleviates salt stress on potato by improving root activity, root/shoot ratio, and antioxidative capacity in shoots and maintaining K+/Na+ homeostasis in potato shoots and roots.

  19. Serotonin inputs to the dorsal BNST modulate anxiety in a 5-HT1A receptor-dependent manner.

    Science.gov (United States)

    Garcia-Garcia, A L; Canetta, S; Stujenske, J M; Burghardt, N S; Ansorge, M S; Dranovsky, A; Leonardo, E D

    2017-08-01

    Serotonin (5-HT) neurons project from the raphe nuclei throughout the brain where they act to maintain homeostasis. Here, we study 5-HT inputs into the bed nucleus of the stria terminalis (BNST), a major subdivision of the extended amygdala that has been proposed to regulate responses to anxiogenic environments in humans and rodents. While the dorsal part of the BNST (dBNST) receives dense 5-HT innervation, whether and how 5-HT in the dBNST normally modulates anxiety remains unclear. Using optogenetics, we demonstrate that activation of 5-HT terminals in the dBNST reduces anxiety in a highly anxiogenic environment. Further analysis revealed that optogenetic inhibition of 5-HT inputs into the dBNST increases anxiety in a less anxiogenic environment. We found that 5-HT predominantly hyperpolarizes dBNST neurons, reducing their activity in a manner that can be blocked by a 5-HT 1A antagonist. Finally, we demonstrate that activation of 5-HT 1A receptors in the dBNST is necessary for the anxiolytic effect observed following optogenetic stimulation of 5-HT inputs into the dBNST. These data reveal that 5-HT release in the dBNST modulates anxiety-like behavior via 5-HT 1A receptors under naturalistic conditions.Molecular Psychiatry advance online publication, 1 August 2017; doi:10.1038/mp.2017.165.

  20. Acetylcholinesterase activity of electric eel is increased or decreased by selected monoterpenoids and phenylpropanoids in a concentration-dependent manner.

    Science.gov (United States)

    López, María Dolores; Campoy, Francisco J; Pascual-Villalobos, María Jesús; Muñoz-Delgado, Encarnación; Vidal, Cecilio J

    2015-03-05

    The profitable insecticidal action of monoterpenoids prompted us to test their efficiency against stored-grain beetle species, via inhibition of acetylcholinesterase (AChE). For this, we first studied the ability of the monoterpenoids geraniol, linalool, camphor, fenchone, carvone and γ-terpinene, besides the phenylpropanoids trans-anethole and estragole to inhibit Electrophorus AChE. The results indicated that while AChE activity increased (15-35%) with 40 μM geraniol, camphor, γ-terpinene and linalool, the activity decreased (60-40%) with 5mM carvone, γ-terpinene, and fenchone. The Km for AChE was 0.52 ± 0.02 mM in control assays, which fell to 0.28 ± 0.01 mM or 0.32 ± 0.01 mM in assays with 20 μM linalool or γ-terpinene added. In the millimolar range, the terpenoids behaved as weak inhibitors. Unexpectedly, AChE inhibition by camphor, carvone, γ-terpinene, and fenchone gave Hill numbers ranging 2.04-1.57, supporting the idea that AChE was able to lodge more than one monoterpenoid molecule. The plots of 1/v vs. 1/S at varying monoterpenoid provided straight lines, fenchone and γ-terpinene acting as competitive inhibitors and carvone and camphor as non-competitive inhibitors. Moreover, the secondary plots of the slope KM(app)/Vmax(app) vs. [I] and of 1/Vmax(app) vs. [I] gave parabolic curves, which lent support to the proposed capacity of AChE to bind more than one monoterpenoid molecule. The fitting of the curves to a second-order polynomial equation allowed us to calculate the inhibition constants for the interaction of AChE with fenchone, γ-terpinene, carvone and camphor. The previously unnoticed increase in AChE activity with monoterpenoids should be considered as a reminder when advising the use of essential oils of plants or their constituents as anti-AChE agents to attenuate pathological signs of Alzheimer's disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.