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Sample records for counteracts gm-csf-mediated increase

  1. Increased nitrogen availability counteracts climatic change feedback from increased temperature on boreal forest soil organic matter degradation

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    Erhagen, Bjorn; Nilsson, Mats; Oquist, Mats; Ilstedt, Ulrik; Sparrman, Tobias; Schleucher, Jurgen

    2014-05-01

    Over the last century, the greenhouse gas concentrations in the atmosphere have increased dramatically, greatly exceeding pre-industrial levels that had prevailed for the preceding 420 000 years. At the same time the annual anthropogenic contribution to the global terrestrial nitrogen cycle has increased and currently exceeds natural inputs. Both temperature and nitrogen levels have profound effects on the global carbon cycle including the rate of organic matter decomposition, which is the most important biogeochemical process that returns CO2 to the atmosphere. Here we show for the first time that increasing the availability of nitrogen not only directly affects the rate of organic matter decomposition but also significantly affects its temperature dependence. We incubated litter and soil organic matter from a long-term (40 years) nitrogen fertilization experiment in a boreal Scots pine (Pinus silvestris L.) forest at different temperatures and determined the temperature dependence of the decomposition of the sample's organic matter in each case. Nitrogen fertilization did not affect the temperature sensitivity (Q10) of the decomposition of fresh plant litter but strongly reduced that for humus soil organic matter. The Q10 response of the 0-3 cm soil layer decreased from 2.5±0.35 to an average of 1.9±0.21 over all nitrogen treatments, and from 2.2±0.19 to 1.6±0.16 in response to the most intense nitrogen fertilization treatment in the 4-7 cm soil layer. Long-term nitrogen additions also significantly affected the organic chemical composition (as determined by 13C CP-MAS NMR spectroscopy) of the soil organic matter. These changes in chemical composition contributed significantly (p<0.05) to the reduced Q10 response. These new insights into the relationship between nitrogen availability and the temperature sensitivity of organic matter decomposition will be important for understanding and predicting how increases in global temperature and rising anthropogenic

  2. Increasing adult hippocampal neurogenesis in mice after exposure to unpredictable chronic mild stress may counteract some of the effects of stress.

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    Culig, Luka; Surget, Alexandre; Bourdey, Marlene; Khemissi, Wahid; Le Guisquet, Anne-Marie; Vogel, Elise; Sahay, Amar; Hen, René; Belzung, Catherine

    2017-11-01

    Major depression is hypothesized to be associated with dysregulations of the hypothalamic-pituitary-adrenal (HPA) axis and impairments in adult hippocampal neurogenesis. Adult-born hippocampal neurons are required for several effects of antidepressants and increasing the rate of adult hippocampal neurogenesis (AHN) before exposure to chronic corticosterone is sufficient to protect against its harmful effects on behavior. However, it is an open question if increasing AHN after the onset of chronic stress exposure would be able to rescue behavioral deficits and which mechanisms might be involved in recovery. We investigated this question by using a 10-week unpredictable chronic mild stress (UCMS) model on a transgenic mouse line (iBax mice), in which the pro-apoptotic gene Bax can be inducibly ablated in neural stem cells following Tamoxifen injection, therefore enhancing the survival of newborn neurons in the adult brain. We did not observe any effect of our treatment in non-stress conditions, but we did find that increasing AHN after 2 weeks of UCMS is sufficient to counteract the effects of UCMS on certain behaviors (splash test and changes in coat state) and endocrine levels and thus to display some antidepressant-like effects. We observed that increasing AHN lowered the elevated basal corticosterone levels in mice exposed to UCMS. This was accompanied by a tamoxifen-induced reversal of the lack of stress-induced decrease in neuronal activation in the anteromedial division of the bed nucleus of the stria terminalis (BSTMA) after intrahippocampal dexamethasone infusion, pointing to a possible mechanism through which adult-born neurons might have exerted their effects. Our results contribute to the neurogenesis hypothesis of depression by suggesting that increasing AHN may be beneficial not just before, but also after exposure to stress by counteracting several of its effects, in part through regulating the HPA axis. Copyright © 2017 Elsevier Ltd. All rights

  3. Ammonium intensifies CAM photosynthesis and counteracts drought effects by increasing malate transport and antioxidant capacity in Guzmania monostachia.

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    Pereira, Paula Natália; Gaspar, Marília; Smith, J Andrew C; Mercier, Helenice

    2018-04-09

    Guzmania monostachia (Bromeliaceae) is a tropical epiphyte capable of up-regulating crassulacean acid metabolism (CAM) in its photosynthetic tissues in response to changing nutrient and water availability. Previous studies have shown that under drought there is a gradient of increasing CAM expression from the basal (youngest) to the apical (oldest) portion of the leaves, and additionally that nitrogen deficiency can further increase CAM intensity in the leaf apex of this bromeliad. The present study investigated the inter-relationships between nitrogen source (nitrate and/or ammonium) and water deficit in regulating CAM expression in G. monostachia leaves. The highest CAM activity was observed under ammonium nutrition in combination with water deficit. This was associated with enhanced activity of the key enzyme phosphoenolpyruvate carboxylase, elevated rates of ATP- and PPi-dependent proton transport at the vacuolar membrane in the presence of malate, and increased transcript levels of the vacuolar malate channel-encoding gene, ALMT. Water deficit was consistently associated with higher levels of total soluble sugars, which were maximal under ammonium nutrition, as were the activities of several antioxidant enzymes (superoxide dismutase, catalase, ascorbate peroxidase, and glutathione reductase). Thus, ammonium nutrition, whilst associated with the highest degree of CAM induction in G. monostachia, also mitigates the effects of water deficit by osmotic adjustment and can limit oxidative damage in the leaves of this bromeliad under conditions that may be typical of its epiphytic habitat.

  4. Black Tea Increases Circulating Endothelial Progenitor Cells and Improves Flow Mediated Dilatation Counteracting Deleterious Effects from a Fat Load in Hypertensive Patients: A Randomized Controlled Study

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    Davide Grassi

    2016-11-01

    Full Text Available (1 Background: Endothelial dysfunction predicts cardiovascular events. Circulating angiogenic cells (CACs maintain and repair the endothelium regulating its function. Tea flavonoids reduce cardiovascular risk. We investigated the effects of black tea on the number of CACs and on flow-mediated dilation (FMD before and after an oral fat in hypertensives; (2 Methods: In a randomized, double-blind, controlled, cross-over study, 19 patients were assigned to black tea (150 mg polyphenols or a placebo twice a day for eight days. Measurements were obtained in a fasted state and after consuming whipping cream, and FMD was measured at baseline and after consumption of the products; (3 Results: Compared with the placebo, black tea ingestion increased functionally active CACs (36 ± 22 vs. 56 ± 21 cells per high-power field; p = 0.006 and FMD (5.0% ± 0.3% vs. 6.6% ± 0.3%, p < 0.0001. Tea further increased FMD 1, 2, 3, and 4 h after consumption, with maximal response 2 h after intake (p < 0.0001. Fat challenge decreased FMD, while tea consumption counteracted FMD impairment (p < 0.0001; (4 Conclusions: We demonstrated the vascular protective properties of black tea by increasing the number of CACs and preventing endothelial dysfunction induced by acute oral fat load in hypertensive patients. Considering that tea is the most consumed beverage after water, our findings are of clinical relevance and interest.

  5. Black Tea Increases Circulating Endothelial Progenitor Cells and Improves Flow Mediated Dilatation Counteracting Deleterious Effects from a Fat Load in Hypertensive Patients: A Randomized Controlled Study

    Science.gov (United States)

    Grassi, Davide; Draijer, Richard; Schalkwijk, Casper; Desideri, Giovambattista; D’Angeli, Anatolia; Francavilla, Sandro; Mulder, Theo; Ferri, Claudio

    2016-01-01

    (1) Background: Endothelial dysfunction predicts cardiovascular events. Circulating angiogenic cells (CACs) maintain and repair the endothelium regulating its function. Tea flavonoids reduce cardiovascular risk. We investigated the effects of black tea on the number of CACs and on flow-mediated dilation (FMD) before and after an oral fat in hypertensives; (2) Methods: In a randomized, double-blind, controlled, cross-over study, 19 patients were assigned to black tea (150 mg polyphenols) or a placebo twice a day for eight days. Measurements were obtained in a fasted state and after consuming whipping cream, and FMD was measured at baseline and after consumption of the products; (3) Results: Compared with the placebo, black tea ingestion increased functionally active CACs (36 ± 22 vs. 56 ± 21 cells per high-power field; p = 0.006) and FMD (5.0% ± 0.3% vs. 6.6% ± 0.3%, p FMD 1, 2, 3, and 4 h after consumption, with maximal response 2 h after intake (p FMD, while tea consumption counteracted FMD impairment (p < 0.0001); (4) Conclusions: We demonstrated the vascular protective properties of black tea by increasing the number of CACs and preventing endothelial dysfunction induced by acute oral fat load in hypertensive patients. Considering that tea is the most consumed beverage after water, our findings are of clinical relevance and interest. PMID:27854314

  6. Vitamin K supplementation increases vitamin K tissue levels but fails to counteract ectopic calcification in a mouse model for pseudoxanthoma elasticum.

    Science.gov (United States)

    Gorgels, Theo G M F; Waarsing, Jan H; Herfs, Marjolein; Versteeg, Daniëlle; Schoensiegel, Frank; Sato, Toshiro; Schlingemann, Reinier O; Ivandic, Boris; Vermeer, Cees; Schurgers, Leon J; Bergen, Arthur A B

    2011-11-01

    Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder in which calcification of connective tissue leads to pathology in skin, eye and blood vessels. PXE is caused by mutations in ABCC6. High expression of this transporter in the basolateral hepatocyte membrane suggests that it secretes an as-yet elusive factor into the circulation which prevents ectopic calcification. Utilizing our Abcc6 (-/-) mouse model for PXE, we tested the hypothesis that this factor is vitamin K (precursor) (Borst et al. 2008, Cell Cycle). For 3 months, Abcc6 (-/-) and wild-type mice were put on diets containing either the minimum dose of vitamin K required for normal blood coagulation or a dose that was 100 times higher. Vitamin K was supplied as menaquinone-7 (MK-7). Ectopic calcification was monitored in vivo by monthly micro-CT scans of the snout, as the PXE mouse model develops a characteristic connective tissue mineralization at the base of the whiskers. In addition, calcification of kidney arteries was measured by histology. Results show that supplemental MK-7 had no effect on ectopic calcification in Abcc6 ( -/- ) mice. MK-7 supplementation increased vitamin K levels (in skin, heart and brain) in wild-type and in Abcc6 (-/-) mice. Vitamin K tissue levels did not depend on Abcc6 genotype. In conclusion, dietary MK-7 supplementation increased vitamin K tissue levels in the PXE mouse model but failed to counteract ectopic calcification. Hence, we obtained no support for the hypothesis that Abcc6 transports vitamin K and that PXE can be cured by increasing tissue levels of vitamin K.

  7. High-fat diet reduces the formation of butyrate, but increases succinate, inflammation, liver fat and cholesterol in rats, while dietary fibre counteracts these effects.

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    Greta Jakobsdottir

    Full Text Available Obesity is linked to type 2 diabetes and risk factors associated to the metabolic syndrome. Consumption of dietary fibres has been shown to have positive metabolic health effects, such as by increasing satiety, lowering blood glucose and cholesterol levels. These effects may be associated with short-chain fatty acids (SCFAs, particularly propionic and butyric acids, formed by microbial degradation of dietary fibres in colon, and by their capacity to reduce low-grade inflammation.To investigate whether dietary fibres, giving rise to different SCFAs, would affect metabolic risk markers in low-fat and high-fat diets using a model with conventional rats for 2, 4 and 6 weeks.Conventional rats were administered low-fat or high-fat diets, for 2, 4 or 6 weeks, supplemented with fermentable dietary fibres, giving rise to different SCFA patterns (pectin - acetic acid; guar gum - propionic acid; or a mixture - butyric acid. At the end of each experimental period, liver fat, cholesterol and triglycerides, serum and caecal SCFAs, plasma cholesterol, and inflammatory cytokines were analysed. The caecal microbiota was analysed after 6 weeks.Fermentable dietary fibre decreased weight gain, liver fat, cholesterol and triglyceride content, and changed the formation of SCFAs. The high-fat diet primarily reduced formation of SCFAs but, after a longer experimental period, the formation of propionic and acetic acids recovered. The concentration of succinic acid in the rats increased in high-fat diets with time, indicating harmful effect of high-fat consumption. The dietary fibre partly counteracted these harmful effects and reduced inflammation. Furthermore, the number of Bacteroides was higher with guar gum, while noticeably that of Akkermansia was highest with the fibre-free diet.

  8. Counteraction of Oxidative Stress by Vitamin E Affects Epigenetic Regulation by Increasing Global Methylation and Gene Expression of MLH1 and DNMT1 Dose Dependently in Caco-2 Cells

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    Katja Zappe

    2018-01-01

    Full Text Available Obesity- or diabetes-induced oxidative stress is discussed as a major risk factor for DNA damage. Vitamin E and many polyphenols exhibit antioxidative activities with consequences on epigenetic regulation of inflammation and DNA repair. The present study investigated the counteraction of oxidative stress by vitamin E in the colorectal cancer cell line Caco-2 under normal (1 g/l and high (4.5 g/l glucose cell culture condition. Malondialdehyde (MDA as a surrogate marker of lipid peroxidation and reactive oxygen species (ROS was analyzed. Gene expression and promoter methylation of the DNA repair gene MutL homolog 1 (MLH1 and the DNA methyltransferase 1 (DNMT1 as well as global methylation by LINE-1 were investigated. Results revealed a dose-dependent counteracting effect of vitamin E on H2O2-induced oxidative stress. Thereby, 10 μM vitamin E proved to be more efficient than did 50 μM in reducing MDA. Further, an induction of MLH1 and DNMT1 gene expression was noticed, accompanied by an increase in global methylation. Whether LINE-1 hypomethylation is a cause or effect of oxidative stress is still unclear. In conclusion, supplementation of exogenous antioxidants like vitamin E in vitro exhibits beneficial effects concerning oxidative stress as well as epigenetic regulation involved in DNA repair.

  9. Intrauterine growth restriction increases circulating mitochondrial DNA and Toll-like receptor 9 expression in adult offspring: could aerobic training counteract these adaptations?

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    Oliveira, V; Silva Junior, S D; de Carvalho, M H C; Akamine, E H; Michelini, L C; Franco, M C

    2017-04-01

    It has been demonstrated that intrauterine growth restriction (IUGR) can program increase cardiometabolic risk. There are also evidences of the correlation between IUGR with low-grade inflammation and, thus can contribute to development of several cardiometabolic comorbidities. Therefore, we investigated the influence of IUGR on circulating mitochondrial DNA (mtDNA)/Toll-like receptor 9 (TLR9) and TNF-α expression in adult offspring. Considering that the aerobic training has anti-inflammatory actions, we also investigated whether aerobic training would improve these inflammatory factors. Pregnant Wistar rats received ad libitum or 50% of ad libitum diet throughout gestation. At 8 weeks of age, male offspring from both groups were randomly assigned to control, trained control, restricted and trained restricted. Aerobic training protocol was performed on a treadmill and after that, we evaluated circulating mtDNA, cardiac protein expression of TLR9, plasma and cardiac TNF-α levels, and left ventricle (LV) mass. We found that IUGR promoted an increase in the circulating mtDNA, TLR9 expression and plasma TNF-α levels. Further, our results revealed that aerobic training can restore mtDNA/TLR9 content and plasma levels of TNF-α among restricted rats. The cardiac TNF-α content and LV mass were not influenced either by IUGR or aerobic training. In conclusion, IUGR can program mtDNA/TLR9 content, which may lead to high levels of TNF-α. However, aerobic training was able to normalize these alterations. These findings evidenced that the association of IUGR and aerobic training seems to exert an important interaction effect regarding pro-inflammatory condition and, aerobic training may be used as a strategy to reduce deleterious adaptations in IUGR offspring.

  10. Shorter Harvest Cycles Counteract Increasing Annual Productivity in Industrial Plantation Forests: Trends from Three Decades of Remote Sensing in Southeastern Brazil

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    McMahon, D.; Jackson, R. B.

    2017-12-01

    Plantation forestry can produce woody biomass many times faster than native vegetation, particularly in the tropical regions where plantations have expanded rapidly in the past three decades. However, activists and practitioners have raised concerns over the sustainability of intensive plantations, suggesting that changes to soil properties may inhibit vegetation growth after multiple harvest cycles. We use a 32-year time series of remotely sensed vegetation indices derived from Landsat data, coupled with recent geospatial and wood volume data from plantation companies, to identify trends in management and vegetation productivity in thousands of individual eucalyptus plantation stands. We find that peak vegetation index values at canopy closure, which are correlated with annual wood volume increment, increase over successive harvest cycles, while the length of each cycle decreases. These opposing trends suggest that the number of harvests required to produce a given wood volume peaks around the second harvest cycle and then declines, likely due to refinement of management practices. Across the region, vegetation index data do not support the hypothesized decrease in productivity over multiple harvest cycles. Additional field data and ongoing soil analyses will complement the remote sensing approach to quantifying plantations' long-term effects on the land they occupy.

  11. Murine remote preconditioning increases glucose uptake and suppresses gluconeogenesis in hepatocytes via a brain-liver neurocircuit, leading to counteracting glucose intolerance.

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    Kurabayashi, Atsushi; Tanaka, Chiharu; Matsumoto, Waka; Naganuma, Seiji; Furihata, Mutsuo; Inoue, Keiji; Kakinuma, Yoshihiko

    2018-05-01

    Our previous study revealed that cyclic hindlimb ischaemia-reperfusion (IR) activates cardiac acetylcholine (ACh) synthesis through the cholinergic nervous system and cell-derived ACh accelerates glucose uptake. However, the mechanisms regulating glucose metabolism in vivo remain unknown. We investigated the effects and mechanisms of IR in mice under pathophysiological conditions. Using IR-subjected male C57BL/6J mice, the effects of IR on blood sugar (BS), glucose uptake, central parasympathetic nervous system (PNS) activity, hepatic gluconeogenic enzyme expression and those of ACh on hepatocellular glucose uptake were assessed. IR decreased BS levels by 20% and increased c-fos immunoreactivity in the center of the PNS (the solitary tract and the dorsal motor vagal nucleus). IR specifically downregulated hepatic gluconeogenic enzyme expression and activities (glucose-6-phosphatase and phosphoenolpyruvate carboxykinase) and accelerated hepatic glucose uptake. Transection of a hepatic vagus nerve branch decreased this uptake and reversed BS decrease. Suppressed gluconeogenic enzyme expression was reversed by intra-cerebroventricular administration of a choline acetyltransferase inhibitor. Moreover, IR significantly attenuated hyperglycaemia in murine model of type I and II diabetes mellitus. IR provides another insight into a therapeutic modality for diabetes mellitus due to regulating gluconeogenesis and glucose-uptake and advocates an adjunctive mode rectifying disturbed glucose metabolism. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. The R-enantiomer of citalopram counteracts escitalopram-induced increase in extracellular 5-HT in the frontal cortex of freely moving rats

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    Mørk, A; Kreilgaard, Mads; Sánchez, C

    2003-01-01

    The selective serotonin (5-HT) reuptake inhibitor, citalopram, is a racemic mixture of an S(+)- and R(-)-enantiomer, escitalopram and R-citalopram, respectively. The present study compares the effects of escitalopram, R-citalopram and citalopram on extracellular levels of 5-HT in the frontal cortex...... of freely moving rats. In addition, co-injection of escitalopram and R-citalopram (ratios 1:2 and 1:4) were assessed. In some experiments escitalopram and R-citalopram were infused into the frontal cortex by reverse microdialysis. Finally, the extracellular level of escitalopram in the frontal cortex...... was studied after administration of escitalopram alone or in combination with R-citalopram. Escitalopram (1.0-3.9 mg/kg, s.c.) produced a greater maximal increase in extracellular 5-HT than citalopram (2.0-8.0 mg/kg, s.c.). R-citalopram (15.6 mg/kg s.c.) did not affect the 5-HT levels. When co-injected, R...

  13. Protein Supplementation Does Not Further Increase Latissimus Dorsi Muscle Fiber Hypertrophy after Eight Weeks of Resistance Training in Novice Subjects, but Partially Counteracts the Fast-to-Slow Muscle Fiber Transition

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    Antonio Paoli

    2016-06-01

    Full Text Available The response to resistance training and protein supplementation in the latissimus dorsi muscle (LDM has never been investigated. We investigated the effects of resistance training (RT and protein supplementation on muscle mass, strength, and fiber characteristics of the LDM. Eighteen healthy young subjects were randomly assigned to a progressive eight-week RT program with a normal protein diet (NP or high protein diet (HP (NP 0.85 vs. HP 1.8 g of protein·kg−1·day−1. One repetition maximum tests, magnetic resonance imaging for cross-sectional muscle area (CSA, body composition, and single muscle fibers mechanical and phenotype characteristics were measured. RT induced a significant gain in strength (+17%, p < 0.0001, whole muscle CSA (p = 0.024, and single muscle fibers CSA (p < 0.05 of LDM in all subjects. Fiber isometric force increased in proportion to CSA (+22%, p < 0.005 and thus no change in specific tension occurred. A significant transition from 2X to 2A myosin expression was induced by training. The protein supplementation showed no significant effects on all measured outcomes except for a smaller reduction of 2X myosin expression. Our results suggest that in LDM protein supplementation does not further enhance RT-induced muscle fiber hypertrophy nor influence mechanic muscle fiber characteristics but partially counteracts the fast-to-slow fiber shift.

  14. ISG15 counteracts Listeria monocytogenes infection

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    Radoshevich, Lilliana; Impens, Francis; Ribet, David; Quereda, Juan J; Nam Tham, To; Nahori, Marie-Anne; Bierne, Hélène; Dussurget, Olivier; Pizarro-Cerdá, Javier; Knobeloch, Klaus-Peter; Cossart, Pascale

    2015-01-01

    ISG15 is an interferon-stimulated, linear di-ubiquitin-like protein, with anti-viral activity. The role of ISG15 during bacterial infection remains elusive. We show that ISG15 expression in nonphagocytic cells is dramatically induced upon Listeria infection. Surprisingly this induction can be type I interferon independent and depends on the cytosolic surveillance pathway, which senses bacterial DNA and signals through STING, TBK1, IRF3 and IRF7. Most importantly, we observed that ISG15 expression restricts Listeria infection in vitro and in vivo. We made use of stable isotope labeling in tissue culture (SILAC) to identify ISGylated proteins that could be responsible for the protective effect. Strikingly, infection or overexpression of ISG15 leads to ISGylation of ER and Golgi proteins, which correlates with increased secretion of cytokines known to counteract infection. Together, our data reveal a previously uncharacterized ISG15-dependent restriction of Listeria infection, reinforcing the view that ISG15 is a key component of the innate immune response. DOI: http://dx.doi.org/10.7554/eLife.06848.001 PMID:26259872

  15. Counteracting the Influence of Peer Smoking on YouTube

    OpenAIRE

    Romer, Daniel; Jamieson, Patrick E.; Jamieson, Kathleen Hall; Jones, Christopher; Sherr, Susan

    2017-01-01

    YouTube, a popular online site for user-generated content, is emerging as a powerful source of peer modeling of smoking. Previous research suggests that in counteracting such influence, health messages may inadvertently increase the perceived prevalence of drug use (a descriptive norm) without reducing its acceptability (injunctive norm). This research tested the ability of health messages to reduce the social acceptability of peer smoking on YouTube despite enhancing its perceived prevalence...

  16. Sustainability and Counteracting Factors to Profit Rate Decline

    DEFF Research Database (Denmark)

    Ougaard, Morten

    2014-01-01

    This paper discusses sustainability implications of barriers to growth as specified in the theory of the long-term falling rate of profit but focusing on the counteracting factors (CFs) specified by Marx. These depend much on political processes and are important in state theory for understanding...... policies of national and international institutions. Fourteen partly overlapping factors are identified and grouped in five categories: increased pressure on labor, geographical expansion, resource efficiency, technological progress, and destruction or devaluation of capital. It is suggested...

  17. Cyber terrorism prevention and counteraction workshop review

    NARCIS (Netherlands)

    Pastukhov, O.M.

    2011-01-01

    A NATO Advanced Training Course (ATC ) on Cyber Terrorism Prevention and Counteraction workshop, held in Kiev on September 27-29, 2010, allowed the participants to share their experiences with experts from Ukraine, a Partnership for Peace country. The participants exchanged their ideas on the ways

  18. Training users to counteract phishing.

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    Mayhorn, Christopher B; Nyeste, Patrick G

    2012-01-01

    Phishing is an increasingly more prevalent form of online, social engineered scams that escalate costs and risks to society year to year. This study demonstrates an association between anti-phishing training techniques used in previous research and individual differences which could affect phishing susceptibility. Results indicated that anti-phishing training in both a simple comic and more complex video game form is helpful in decreasing phishing susceptibility as measured by Miss rates for all individuals including college aged and computer savvy participants. Based on the results of the present study, implications for future efforts to combat phishing are discussed.

  19. PPARgamma Deficiency Counteracts Thymic Senescence

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    David Ernszt

    2017-11-01

    Full Text Available Thymic senescence contributes to increased incidence of infection, cancer and autoimmunity at senior ages. This process manifests as adipose involution. As with other adipose tissues, thymic adipose involution is also controlled by PPARgamma. This is supported by observations reporting that systemic PPARgamma activation accelerates thymic adipose involution. Therefore, we hypothesized that decreased PPARgamma activity could prevent thymic adipose involution, although it may trigger metabolic adverse effects. We have confirmed that both human and murine thymic sections show marked staining for PPARgamma at senior ages. We have also tested the thymic lobes of PPARgamma haplo-insufficient and null mice. Supporting our working hypothesis both adult PPARgamma haplo-insufficient and null mice show delayed thymic senescence by thymus histology, thymocyte mouse T-cell recombination excision circle qPCR and peripheral blood naive T-cell ratio by flow-cytometry. Delayed senescence showed dose–response with respect to PPARgamma deficiency. Functional immune parameters were also evaluated at senior ages in PPARgamma haplo-insufficient mice (null mice do not reach senior ages due to metabolic adverse affects. As expected, sustained and elevated T-cell production conferred oral tolerance and enhanced vaccination efficiency in senior PPARgamma haplo-insufficient, but not in senior wild-type littermates according to ELISA IgG measurements. Of note, humans also show increased oral intolerance issues and decreased protection by vaccines at senior ages. Moreover, PPARgamma haplo-insufficiency also exists in human known as a rare disease (FPLD3 causing metabolic adverse effects, similar to the mouse. When compared to age- and metabolic disorder-matched other patient samples (FPLD2 not affecting PPARgamma activity, FPLD3 patients showed increased human Trec (hTrec values by qPCR (within healthy human range suggesting delayed thymic senescence, in accordance with

  20. Counteracting loneliness: on the restorative function of nostalgia.

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    Zhou, Xinyue; Sedikides, Constantine; Wildschut, Tim; Gao, Ding-Guo

    2008-10-01

    Four studies tested whether nostalgia can counteract reductions in perceived social support caused by loneliness. Loneliness reduced perceptions of social support but increased nostalgia. Nostalgia, in turn, increased perceptions of social support. Thus, loneliness affected perceived social support in two distinct ways. Whereas the direct effect of loneliness was to reduce perceived social support, the indirect effect of loneliness was to increase perceived social support via nostalgia. This restorative function of nostalgia was particularly apparent among resilient persons. Nostalgia is a psychological resource that protects and fosters mental health.

  1. Counteracting age-related loss of skeletal muscle mass

    DEFF Research Database (Denmark)

    Bechshøft, Rasmus; Reitelseder, Søren; Højfeldt, Grith

    2016-01-01

    Background Aging is associated with decreased muscle mass and functional capacity, which in turn decrease quality of life. The number of citizens over the age of 65 years in the Western world will increase by 50 % over the next four decades, and this demographic shift brings forth new challenges...... at both societal and individual levels. Only a few longitudinal studies have been reported, but whey protein supplementation seems to improve muscle mass and function, and its combination with heavy strength training appears even more effective. However, heavy resistance training may reduce adherence...... Intervention Study will generate scientific evidence and recommendations to counteract age-related loss of skeletal muscle mass in elderly individuals....

  2. Acidification counteracts negative effects of warming on diatom silicification

    KAUST Repository

    Coello-Camba, Alexandra

    2016-10-24

    Diatoms are a significant group contributing up to 40 % of annual primary production in the oceans. They have a special siliceous cell wall that, acting as a ballast, plays a key role in the sequestration of global carbon and silica. Diatoms dominate primary production in the Arctic Ocean, where global climate change is causing increases in water temperature and in the partial pressure of CO2 (pCO2). Here we show that as water temperature increases diatoms become stressed, grow to smaller sizes, and decrease their silicification rates. But at higher pCO2, as the pH of seawater decreases, silica incorporation rates are increased. In a future warmer Arctic ocean diatoms may have a competitive advantage under increased ocean acidification, as increased pCO2 counteracts the adverse effects of increasing temperature on silicification and buffers its consequences in the biogeochemical cycles of carbon and silica.

  3. Acidification counteracts negative effects of warming on diatom silicification

    KAUST Repository

    Coello-Camba, Alexandra; Agusti, Susana

    2016-01-01

    Diatoms are a significant group contributing up to 40 % of annual primary production in the oceans. They have a special siliceous cell wall that, acting as a ballast, plays a key role in the sequestration of global carbon and silica. Diatoms dominate primary production in the Arctic Ocean, where global climate change is causing increases in water temperature and in the partial pressure of CO2 (pCO2). Here we show that as water temperature increases diatoms become stressed, grow to smaller sizes, and decrease their silicification rates. But at higher pCO2, as the pH of seawater decreases, silica incorporation rates are increased. In a future warmer Arctic ocean diatoms may have a competitive advantage under increased ocean acidification, as increased pCO2 counteracts the adverse effects of increasing temperature on silicification and buffers its consequences in the biogeochemical cycles of carbon and silica.

  4. Testing can counteract proactive interference by integrating competing information

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    Wahlheim, Christopher N.

    2015-01-01

    Testing initially learned information before presenting new information has been shown to counteract the deleterious effects of proactive interference by segregating competing sources of information. The present experiments were conducted to demonstrate that testing can also have its effects in part by integrating competing information. Variations of classic A–B, A–D paired-associate learning paradigms were employed that included two lists of word pairs and a cued-recall test. Repeated pairs appeared in both lists (A–B, A–B), control pairs appeared in List 2 only (A–B, C–D), and changed pairs appeared with the same cue in both lists but with different responses (A–B, A–D). The critical manipulation was whether pairs were tested or restudied in an interpolated phase that occurred between Lists 1 and 2. On a final cued-recall test, participants recalled List 2 responses and then indicated when they recollected that responses had earlier changed between lists. The change recollection measure indexed the extent to which competing responses were integrated during List 2. Change was recollected more often for tested than for restudied pairs. Proactive facilitation was obtained in cued recall when change was recollected, whereas proactive interference was obtained when change was not recollected. These results provide evidence that testing counteracted proactive interference in part by making List 1 responses more accessible during List 2, thus promoting integration and increasing later recollection of change. These results have theoretical implications because they show that testing can counteract proactive interference by integrating or segregating competing information. PMID:25120241

  5. Testing can counteract proactive interference by integrating competing information.

    Science.gov (United States)

    Wahlheim, Christopher N

    2015-01-01

    Testing initially learned information before presenting new information has been shown to counteract the deleterious effects of proactive interference by segregating competing sources of information. The present experiments were conducted to demonstrate that testing can also have its effects in part by integrating competing information. Variations of classic A-B, A-D paired-associate learning paradigms were employed that included two lists of word pairs and a cued-recall test. Repeated pairs appeared in both lists (A-B, A-B), control pairs appeared in List 2 only (A-B, C-D), and changed pairs appeared with the same cue in both lists but with different responses (A-B, A-D). The critical manipulation was whether pairs were tested or restudied in an interpolated phase that occurred between Lists 1 and 2. On a final cued-recall test, participants recalled List 2 responses and then indicated when they recollected that responses had earlier changed between lists. The change recollection measure indexed the extent to which competing responses were integrated during List 2. Change was recollected more often for tested than for restudied pairs. Proactive facilitation was obtained in cued recall when change was recollected, whereas proactive interference was obtained when change was not recollected. These results provide evidence that testing counteracted proactive interference in part by making List 1 responses more accessible during List 2, thus promoting integration and increasing later recollection of change. These results have theoretical implications because they show that testing can counteract proactive interference by integrating or segregating competing information.

  6. Counteracting wetland overgrowth increases breeding and staging bird abundances

    Science.gov (United States)

    Lehikoinen, Petteri; Lehikoinen, Aleksi; Mikkola-Roos, Markku; Jaatinen, Kim

    2017-01-01

    Human actions have led to loss and degradation of wetlands, impairing their suitability as habitat especially for waterbirds. Such negative effects may be mitigated through habitat management. To date scientific evidence regarding the impacts of these actions remains scarce. We studied guild specific abundances of breeding and staging birds in response to habitat management on 15 Finnish wetlands. In this study management actions comprised several means of vegetation removal to thwart overgrowth. Management cost efficiency was assessed by examining the association between site-specific costs and bird abundances. Several bird guilds exhibited positive connections with both habitat management as well as with invested funds. Most importantly, however, red-listed species and species with special conservation concern as outlined by the EU showed positive correlations with management actions, underlining the conservation value of wetland management. The results suggest that grazing was especially efficient in restoring overgrown wetlands. As a whole this study makes it clear that wetland habitat management constitutes a feasible conservation tool. The marked association between invested funds and bird abundance may prove to be a valuable tool for decision makers when balancing costs and impact of conservation measures against one another.

  7. Discourse on corruption counteraction in network trade

    Directory of Open Access Journals (Sweden)

    Leonid A. Zhigun

    2015-12-01

    Full Text Available Objective to determine the specific forms of corruption and promising methods to counteract corruption in network trade. Methods the combination of inductive observations comparisons generalizations facts and trends of corruption in network trade with a logical analytical deduction of economic theories and the corruption concept are the basis of the study and provide an opportunity on the one hand to assess the level of compliance of theoretical concepts of corruption with the practice and on the other handnbsp to determine their applicability to organize opposition and create conditions to prevent its occurrence to summarize the features of corruption in the form of a kickback the discourse method was applied in this work. Results on the basis of theoretical provisions and facts of corruption in trade it is proved that it has typical characteristics of corruption in commercial and nonprofit organizations. The key reasons are identified why corruption occurs in trade. Among them supply of poor quality goods at inflated prices leading to bribery in the form of laquopersonal bonusraquo to administrator of the trading organization when selling goods by an unscrupulous supplier and also supply goods to the trade organizations which will not buy without kickback. Most of these corrupt deals are carried out by natural monopolies in the form of state and municipal procurement. In some cases the kickback is the argument stimulating the decision to introduce new and advanced technologies. The factors that lead to corruption in trade are listed and reasonable methods to counteract it are grounded allowing to create conditions for its eradication in other branches of business as well. Scientific novelty for the first time a generalization has been made about the deficit as the driving force in the mechanism when the bribegivers and bribetakers change places. Practical significance the main provisions and conclusions of the article can be used in the

  8. Sialyltransferase activity probably counteracts that of sialidase as ...

    African Journals Online (AJOL)

    Sialyltransferase activity probably counteracts that of sialidase as one of the possible mechanisms of natural recovery or stabilization of erythrocyte mass in trypanosome-infected animals - A perspective.

  9. Exposure to nature counteracts aggression after depletion.

    Science.gov (United States)

    Wang, Yan; She, Yihan; Colarelli, Stephen M; Fang, Yuan; Meng, Hui; Chen, Qiuju; Zhang, Xin; Zhu, Hongwei

    2018-01-01

    Acts of self-control are more likely to fail after previous exertion of self-control, known as the ego depletion effect. Research has shown that depleted participants behave more aggressively than non-depleted participants, especially after being provoked. Although exposure to nature (e.g., a walk in the park) has been predicted to replenish resources common to executive functioning and self-control, the extent to which exposure to nature may counteract the depletion effect on aggression has yet to be determined. The present study investigated the effects of exposure to nature on aggression following depletion. Aggression was measured by the intensity of noise blasts participants delivered to an ostensible opponent in a competition reaction-time task. As predicted, an interaction occurred between depletion and environmental manipulations for provoked aggression. Specifically, depleted participants behaved more aggressively in response to provocation than non-depleted participants in the urban condition. However, provoked aggression did not differ between depleted and non-depleted participants in the natural condition. Moreover, within the depletion condition, participants in the natural condition had lower levels of provoked aggression than participants in the urban condition. This study suggests that a brief period of nature exposure may restore self-control and help depleted people regain control over aggressive urges. © 2017 Wiley Periodicals, Inc.

  10. Does comorbid anxiety counteract emotion recognition deficits in conduct disorder?

    Science.gov (United States)

    Short, Roxanna M L; Sonuga-Barke, Edmund J S; Adams, Wendy J; Fairchild, Graeme

    2016-08-01

    Previous research has reported altered emotion recognition in both conduct disorder (CD) and anxiety disorders (ADs) - but these effects appear to be of different kinds. Adolescents with CD often show a generalised pattern of deficits, while those with ADs show hypersensitivity to specific negative emotions. Although these conditions often cooccur, little is known regarding emotion recognition performance in comorbid CD+ADs. Here, we test the hypothesis that in the comorbid case, anxiety-related emotion hypersensitivity counteracts the emotion recognition deficits typically observed in CD. We compared facial emotion recognition across four groups of adolescents aged 12-18 years: those with CD alone (n = 28), ADs alone (n = 23), cooccurring CD+ADs (n = 20) and typically developing controls (n = 28). The emotion recognition task we used systematically manipulated the emotional intensity of facial expressions as well as fixation location (eye, nose or mouth region). Conduct disorder was associated with a generalised impairment in emotion recognition; however, this may have been modulated by group differences in IQ. AD was associated with increased sensitivity to low-intensity happiness, disgust and sadness. In general, the comorbid CD+ADs group performed similarly to typically developing controls. Although CD alone was associated with emotion recognition impairments, ADs and comorbid CD+ADs were associated with normal or enhanced emotion recognition performance. The presence of comorbid ADs appeared to counteract the effects of CD, suggesting a potentially protective role, although future research should examine the contribution of IQ and gender to these effects. © 2016 Association for Child and Adolescent Mental Health.

  11. Coronavirus gene 7 counteracts host defenses and modulates virus virulence.

    Directory of Open Access Journals (Sweden)

    Jazmina L G Cruz

    2011-06-01

    Full Text Available Transmissible gastroenteritis virus (TGEV genome contains three accessory genes: 3a, 3b and 7. Gene 7 is only present in members of coronavirus genus a1, and encodes a hydrophobic protein of 78 aa. To study gene 7 function, a recombinant TGEV virus lacking gene 7 was engineered (rTGEV-Δ7. Both the mutant and the parental (rTGEV-wt viruses showed the same growth and viral RNA accumulation kinetics in tissue cultures. Nevertheless, cells infected with rTGEV-Δ7 virus showed an increased cytopathic effect caused by an enhanced apoptosis mediated by caspase activation. Macromolecular synthesis analysis showed that rTGEV-Δ7 virus infection led to host translational shut-off and increased cellular RNA degradation compared with rTGEV-wt infection. An increase of eukaryotic translation initiation factor 2 (eIF2α phosphorylation and an enhanced nuclease, most likely RNase L, activity were observed in rTGEV-Δ7 virus infected cells. These results suggested that the removal of gene 7 promoted an intensified dsRNA-activated host antiviral response. In protein 7 a conserved sequence motif that potentially mediates binding to protein phosphatase 1 catalytic subunit (PP1c, a key regulator of the cell antiviral defenses, was identified. We postulated that TGEV protein 7 may counteract host antiviral response by its association with PP1c. In fact, pull-down assays demonstrated the interaction between TGEV protein 7, but not a protein 7 mutant lacking PP1c binding motif, with PP1. Moreover, the interaction between protein 7 and PP1 was required, during the infection, for eIF2α dephosphorylation and inhibition of cell RNA degradation. Inoculation of newborn piglets with rTGEV-Δ7 and rTGEV-wt viruses showed that rTGEV-Δ7 virus presented accelerated growth kinetics and pathology compared with the parental virus. Overall, the results indicated that gene 7 counteracted host cell defenses, and modified TGEV persistence increasing TGEV survival. Therefore, the

  12. Counteracting the Influence of Peer Smoking on YouTube.

    Science.gov (United States)

    Romer, Daniel; Jamieson, Patrick E; Jamieson, Kathleen Hall; Jones, Christopher; Sherr, Susan

    2017-04-01

    YouTube, a popular online site for user-generated content, is emerging as a powerful source of peer modeling of smoking. Previous research suggests that in counteracting such influence, health messages may inadvertently increase the perceived prevalence of drug use (a descriptive norm) without reducing its acceptability (injunctive norm). This research tested the ability of health messages to reduce the social acceptability of peer smoking on YouTube despite enhancing its perceived prevalence. In an online experiment with 999 adolescents, participants were randomly assigned to view one of two videos: (a) a mosaic displaying a variety of YouTube videos of adolescents smoking followed by a message about the mortality risk to those smokers, or (b) a control video on a health topic unrelated to smoking. Although exposure to the adolescent YouTube smokers increased perceived prevalence among some participants, it simultaneously increased beliefs about smoking's adverse health outcomes and negative attitudes toward smoking, effects that were associated with reductions in injunctive norms of social acceptability. Interventions that communicate the severity and scope of health risks associated with smoking may undercut the descriptive normative effects of peer modeling of smoking on social media sites such as YouTube.

  13. Counteracting fatigue in multiple sclerosis with right parietal anodal transcranial direct current stimulation

    OpenAIRE

    Katrin Hanken; Katrin Hanken; Mona Bosse; Kim Möhrke; Paul Eling; Andreas Kastrup; Andrea Antal; Helmut Hildebrandt; Helmut Hildebrandt

    2016-01-01

    Background: Fatigue in multiple sclerosis (MS) patients appears to correlate with vigilance decrement as reflected in an increase in reaction time and errors with prolonged time-on-task. Objectives: The aim of this study was to investigate whether anodal transcranial direct current stimulation (tDCS) over the right parietal or frontal cortex counteracts fatigue-associated vigilance decrement and subjective fatigue. Methods: In study I, a randomized double-blind placebo-controlled study, anoda...

  14. Counteracting Fatigue in Multiple Sclerosis with Right Parietal Anodal Transcranial Direct Current Stimulation

    OpenAIRE

    Hanken, Katrin; Bosse, Mona; M?hrke, Kim; Eling, Paul; Kastrup, Andreas; Antal, Andrea; Hildebrandt, Helmut

    2016-01-01

    BACKGROUND: Fatigue in multiple sclerosis (MS) patients appears to correlate with vigilance decrement as reflected in an increase in reaction time (RT) and errors with prolonged time-on-task. OBJECTIVES: The aim of this study was to investigate whether anodal transcranial direct current stimulation (tDCS) over the right parietal or frontal cortex counteracts fatigue-associated vigilance decrement and subjective fatigue. METHODS: In study I, a randomized double-blind placebo-controll...

  15. Counteracting venous stasis during acute lower leg immobilization.

    NARCIS (Netherlands)

    Poelkens, F.; Thijssen, D.H.J.; Kersten, B.T.P.; Scheurwater, H.; Laarhoven, E.W. van; Hopman, M.T.E.

    2006-01-01

    AIM: During lower limb immobilization, patients are at risk to develop deep venous thrombosis. Recently, a water-pad was developed that should counteract venous stasis. The water-pad, located under the plaster, mobilizes water from the foot to the calf during weight bearing and, thereby, imitates

  16. Counteracting Age Stereotypes: A Self-Awareness Manipulation

    Science.gov (United States)

    Chen, Yiwei; Pethtel, Olivia; Ma, Xiaodong

    2010-01-01

    The major goals of the present study were to (a) examine age differences in susceptibility to age stereotypes and (b) test a self-awareness manipulation in counteracting age stereotypes. Young and older adults read two sets of descriptors that only differed in the to-be-ignored age-related information. In the high self-awareness condition,…

  17. Counteracting fatigue in multiple sclerosis with right parietal anodal transcranial direct current stimulation

    Directory of Open Access Journals (Sweden)

    Katrin Hanken

    2016-09-01

    Full Text Available Background: Fatigue in multiple sclerosis (MS patients appears to correlate with vigilance decrement as reflected in an increase in reaction time and errors with prolonged time-on-task. Objectives: The aim of this study was to investigate whether anodal transcranial direct current stimulation (tDCS over the right parietal or frontal cortex counteracts fatigue-associated vigilance decrement and subjective fatigue. Methods: In study I, a randomized double-blind placebo-controlled study, anodal tDCS (1,5mA was delivered to the right parietal cortex or the right frontal cortex of 52 healthy participants during the first 20min of a 40min lasting visual vigilance task. Study II, also a randomized double-blind placebo-controlled study, investigated the effect of anodal tDCS (1.5mA over the right parietal cortex in 46 MS patients experiencing cognitive fatigue. TDCS was delivered for 20min before patients performed a 20min lasting visual vigilance task.Results: Study I showed that right parietal stimulation, but not right frontal stimulation, counteracts the increase in reaction time associated with vigilance decrement. Hence, only right parietal stimulation was applied to the MS patients in study II. Stimulation had a significant effect on vigilance decrement in mildly to moderately cognitively fatigued MS patients. Vigilance testing significantly increased the feeling of fatigue independent of stimulation.Conclusions: Anodal tDCS over the right parietal cortex can counteract the increase in reaction times during vigilance performance but not the increase in subjective fatigue. This finding is compatible with our model of fatigue in MS, suggesting a dissociation between the feeling and the behavioral characteristics of fatigue.

  18. Counteracting Fatigue in Multiple Sclerosis with Right Parietal Anodal Transcranial Direct Current Stimulation.

    Science.gov (United States)

    Hanken, Katrin; Bosse, Mona; Möhrke, Kim; Eling, Paul; Kastrup, Andreas; Antal, Andrea; Hildebrandt, Helmut

    2016-01-01

    Fatigue in multiple sclerosis (MS) patients appears to correlate with vigilance decrement as reflected in an increase in reaction time (RT) and errors with prolonged time-on-task. The aim of this study was to investigate whether anodal transcranial direct current stimulation (tDCS) over the right parietal or frontal cortex counteracts fatigue-associated vigilance decrement and subjective fatigue. In study I, a randomized double-blind placebo-controlled study, anodal tDCS (1.5 mA) was delivered to the right parietal cortex or the right frontal cortex of 52 healthy participants during the first 20 min of a 40-min lasting visual vigilance task. Study II, also a randomized double-blind placebo-controlled study, investigated the effect of anodal tDCS (1.5 mA) over the right parietal cortex in 46 MS patients experiencing cognitive fatigue. tDCS was delivered for 20 min before patients performed a 20-min lasting visual vigilance task. Study I showed that right parietal stimulation, but not right frontal stimulation, counteracts the increase in RT associated with vigilance decrement. Hence, only right parietal stimulation was applied to the MS patients in study II. Stimulation had a significant effect on vigilance decrement in mildly to moderately cognitively fatigued MS patients. Vigilance testing significantly increased the feeling of fatigue independent of stimulation. Anodal tDCS over the right parietal cortex can counteract the increase in RTs during vigilance performance, but not the increase in subjective fatigue. This finding is compatible with our model of fatigue in MS, suggesting a dissociation between the feeling and the behavioral characteristics of fatigue.

  19. High-Intensity Interval Training as a Tool for Counteracting Dyslipidemia in Women.

    Science.gov (United States)

    Alvarez, Cristian; Ramirez-Campillo, Rodrigo; Martinez-Salazar, Cristian; Castillo, Angélica; Gallardo, Francisco; Ciolac, Emmanuel Gomes

    2018-05-01

    Sedentary overweight or obese adult (agehigh-intensity interval training (HIIT) program. Triglycerides reduced significantly ( P high-density lipoprotein increased ( P body composition improved ( P <0.05) in all groups. The HIIT program was effective for restoring lipid profile of DYS and DYSHG, and fasting glucose of DYSHG to levels similar to those of CON, with a weekly time commitment 25% to 56% lower than the minimum recommended in current exercise guidelines. These findings suggest that HIIT may be a time-efficient intervention for counteracting dyslipidemia. © Georg Thieme Verlag KG Stuttgart · New York.

  20. COUNTERACTING AGE STEREOTYPES: A SELF-AWARENESS MANIPULATION

    OpenAIRE

    Chen, Yiwei; Pethtel, Olivia; Ma, Xiaodong

    2010-01-01

    The major goals of the present study were to (a) examine age differences in susceptibility to age stereotypes and (b) test a self-awareness manipulation in counteracting age stereotypes. Young and older adults read two sets of descriptors that only differed in the to-be-ignored age-related information. In the high self-awareness condition, participants saw themselves via a computer video camera. In the low self-awareness condition, they saw prerecorded images of a stranger. Overall, older adu...

  1. Topical legal aspects of corruption counteraction in public procurement

    Directory of Open Access Journals (Sweden)

    Aleksandr Igorevich Zemlin

    2015-03-01

    Full Text Available Objective to analyze the current developments in the Russian legislation on corruption counteraction and the legislation on public procurement system on this basis to study legal conflicts and gaps and to develop proposals under the provisions of the National AntiCorruption Plan for 2014ndash2015. Methods historical formallegal logical and systemicfunctional structural and contextual approach to the study of law and theoretical propositions concerning the definition nature and characteristics of legal relations arising in the process of and relating to the corruption counteraction in the public procurement system. Results аn aggregate of theoretical conclusions and proposals aimed at perfection of anticorruption legislation and legislation on the contractual public procurement system is presented. Scientific novelty the results of the author39s interpretation of changes in the Russian anticorruption legislation and legislation on the contractual public procurement system existing legal conflicts and gaps. Practical significance developing proposals for improving the standards of anticorruption legislation and legislation on public procurement system under the provisions of the National AntiCorruption Plan for 2014ndash2015. nbsp

  2. Tamoxifen counteracts estradiol induced effects on striatal and hypophyseal dopamine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Ferretti, C.; Blengio, M.; Ghi, P.; Racca, S.; Genazzani, E.; Portaleone, P.

    1988-01-01

    We investigated the ability of Tamoxifen (TAM), an antiestrogen drug, to counteract the modification induced by estrogens on dopamine (DA) receptors on striatum and on adenohypophysis of ovex female rats. Subacute treatment with 17..beta..-estradiol (E/sub 2/) at both low (0.1 ..mu..g/kg) and high (20 ..mu..g/kg) doses confirmed its ability to increase the number of striatal /sup 3/H-Spiperone (/sup 3/H-SPI) binding sites in a dose dependent manner. By contrast in the pituitary, only high doses of estrogen were effective in reducing the number of DA receptors. We treated ovex female rats for 15 days with TAM alone or associated with E/sub 2/, to see if these estrogenic effects could be suppressed by an antiestrogenic drug. TAM did not affect the number of striatal DA receptors, but significantly increased the adenohypophy-seal DA binding sites, without varying their affinity. No changes were observed in pituitary and striatal DA receptor density, even when TAM was injected in association with estradiol. In conclusions: TAM is able to counteract the effects estrogens have on DA receptors. However there is some evidence that it could influence the pituitary DA systems independently of it antiestrogenic activity.

  3. Olopatadine Inhibits Exocytosis in Rat Peritoneal Mast Cells by Counteracting Membrane Surface Deformation

    Directory of Open Access Journals (Sweden)

    Asuka Baba

    2015-01-01

    Full Text Available Backgroud/Aims: Besides its anti-allergic properties as a histamine receptor antagonist, olopatadine stabilizes mast cells by inhibiting the release of chemokines. Since olopatadine bears amphiphilic features and is preferentially partitioned into the lipid bilayers of the plasma membrane, it would induce some morphological changes in mast cells and thus affect the process of exocytosis. Methods: Employing the standard patch-clamp whole-cell recording technique, we examined the effects of olopatadine and other anti-allergic drugs on the membrane capacitance (Cm in rat peritoneal mast cells during exocytosis. Using confocal imaging of a water-soluble fluorescent dye, lucifer yellow, we also examined their effects on the deformation of the plasma membrane. Results: Low concentrations of olopatadine (1 or 10 µM did not significantly affect the GTP-γ-S-induced increase in the Cm. However, 100 µM and 1 mM olopatadine almost totally suppressed the increase in the Cm. Additionally, these doses completely washed out the trapping of the dye on the cell surface, indicating that olopatadine counteracted the membrane surface deformation induced by exocytosis. As shown by electron microscopy, olopatadine generated inward membrane bending in mast cells. Conclusion: This study provides electrophysiological evidence for the first time that olopatadine dose-dependently inhibits the process of exocytosis in rat peritoneal mast cells. Such mast cell stabilizing properties of olopatadine may be attributed to its counteracting effects on the plasma membrane deformation in degranulating mast cells.

  4. Tamoxifen counteracts estradiol induced effects on striatal and hypophyseal dopamine receptors

    International Nuclear Information System (INIS)

    Ferretti, C.; Blengio, M.; Ghi, P.; Racca, S.; Genazzani, E.; Portaleone, P.

    1988-01-01

    We investigated the ability of Tamoxifen (TAM), an antiestrogen drug, to counteract the modification induced by estrogens on dopamine (DA) receptors on striatum and on adenohypophysis of ovex female rats. Subacute treatment with 17β-estradiol (E 2 ) at both low (0.1 μg/kg) and high (20 μg/kg) doses confirmed its ability to increase the number of striatal 3 H-Spiperone ( 3 H-SPI) binding sites in a dose dependent manner. By contrast in the pituitary, only high doses of estrogen were effective in reducing the number of DA receptors. We treated ovex female rats for 15 days with TAM alone or associated with E 2 , to see if these estrogenic effects could be suppressed by an antiestrogenic drug. TAM did not affect the number of striatal DA receptors, but significantly increased the adenohypophy-seal DA binding sites, without varying their affinity. No changes were observed in pituitary and striatal DA receptor density, even when TAM was injected in association with estradiol. In conclusions: TAM is able to counteract the effects estrogens have on DA receptors. However there is some evidence that it could influence the pituitary DA systems independently of it antiestrogenic activity

  5. Current means for raising efficiency of counteraction to counterfeit goods trafficking

    Directory of Open Access Journals (Sweden)

    Dronova O.B.

    2014-12-01

    Full Text Available The urgency of counteraction to counterfeit goods trafficking is shown. Annual loss due to counterfeit goods producing and trafficking reaches several billion dollars. There remains a danger of buying low-quality and counterfeit goods despite implementing new producing techniques and protective elements. Measures, taken by law enforcement agencies, state authorities and public human rights organizations have not led to systematic suppression of producing and trafficking of such goods. Creation of new information and reference resource, containing information blocks of protective symbols on goods and packages and illustrated materials comprising patterns of discovered counterfeit goods, can assist to increase public awareness and to give necessary information to law enforcement agencies. Organizations, realizing state and social protection of consumers and entrepreneurs, along with producers, rightholders’ representatives and law enforcement bodies can accept the responsibility of creating and functioning this information and reference system in the Internet. Such level of cooperation of all interested organizations will allow to raise efficiency of measures for counteraction to trafficking goods with violated consumer properties. The author proves the necessity to organize functioning of information and reference resource for a wide range of users. Operation of such resource should comply with main principles of generating any information resource, notably full scale, authenticity and relevance of information. The author proposes the algorithm of creating such system which provides cooperation of law enforcement agencies, producers and consumers for the purpose of preventing counterfeit goods trafficking and investigating committed crimes.

  6. Effect of IR Laser on Myoblasts: Prospects of Application for Counteracting Microgravity-Induced Muscle Atrophy

    Science.gov (United States)

    Monici, Monica; Cialdai, Francesca; Romano, Giovanni; Corsetto, Paola Antonia; Rizzo, Angela Maria; Caselli, Anna; Ranaldi, Francesco

    2013-02-01

    Microgravity-induced muscle atrophy is a problem of utmost importance for the impact it may have on the health and performance of astronauts. Therefore, appropriate countermeasures are needed to prevent disuse atrophy and favour muscle recovery. Muscle atrophy is characterized by loss of muscle mass and strength, and a shift in substrate utilization from fat to glucose, that leads to a reduced metabolic efficiency and enhanced fatigability. Laser therapy is already used in physical medicine and rehabilitation to accelerate muscle recovery and in sports medicine to prevent damages produced by metabolic disturbances and inflammatory reactions after heavy exercise. The aim of the research we present was to get insights on possible benefits deriving from the application of an advanced infrared laser system to counteract deficits of muscle energy metabolism and stimulate the recovery of the hypotrophic tissue. The source used was a Multiwave Locked System (MLS) laser, which combines continuous and pulsed emissions at 808 nm and 905 nm, respectively. We studied the effect of MLS treatment on morphology and energy metabolism of C2C12 cells, a widely accepted myoblast model, previously exposed to microgravity conditions modelled by a Random Positioning Machine. The MLS laser treatment was able to restore basal levels of serine/threonine protein phosphatase activity and to counteract cytoskeletal alterations and increase in glycolytic enzymes activity that occurred following the exposure to modelled microgravity. In conclusion, the results provide interesting insights for the application of infrared laser in the treatment of muscle atrophy.

  7. Counteracting effect of threat on reward enhancements during working memory.

    Science.gov (United States)

    Choi, Jong Moon; Padmala, Srikanth; Pessoa, Luiz

    2015-01-01

    Cognitive performance has been shown to be enhanced when performance-based rewards are at stake. On the other hand, task-irrelevant threat processing has been shown to have detrimental effects during several cognitive tasks. Crucially, the impact of reward and threat on cognition has been studied largely independently of one another. Hence, our understanding of how reward and threat simultaneously contribute to performance is incomplete. To fill in this gap, the present study investigated how reward and threat interact with one another during a cognitive task. We found that threat of shock counteracted the beneficial effect of reward during a working memory task. Furthermore, individual differences in self-reported reward-sensitivity and anxiety were linked to the extent to which reward and threat interacted during behaviour. Together, the current findings contribute to a limited but growing literature unravelling how positive and negative information processing jointly influence cognition.

  8. Propionyl-L-Carnitine Enhances Wound Healing and Counteracts Microvascular Endothelial Cell Dysfunction.

    Directory of Open Access Journals (Sweden)

    Maria Giovanna Scioli

    Full Text Available Impaired wound healing represents a high cost for health care systems. Endothelial dysfunction characterizes dermal microangiopathy and contributes to delayed wound healing and chronic ulcers. Endothelial dysfunction impairs cutaneous microvascular blood flow by inducing an imbalance between vasorelaxation and vasoconstriction as a consequence of reduced nitric oxide (NO production and the increase of oxidative stress and inflammation. Propionyl-L-carnitine (PLC is a natural derivative of carnitine that has been reported to ameliorate post-ischemic blood flow recovery.We investigated the effects of PLC in rat skin flap and cutaneous wound healing. A daily oral PLC treatment improved skin flap viability and associated with reactive oxygen species (ROS reduction, inducible nitric oxide synthase (iNOS and NO up-regulation, accelerated wound healing and increased capillary density, likely favoring dermal angiogenesis by up-regulation for iNOS, vascular endothelial growth factor (VEGF, placental growth factor (PlGF and reduction of NADPH-oxidase 4 (Nox4 expression. In serum-deprived human dermal microvascular endothelial cell cultures, PLC ameliorated endothelial dysfunction by increasing iNOS, PlGF, VEGF receptors 1 and 2 expression and NO level. In addition, PLC counteracted serum deprivation-induced impairment of mitochondrial β-oxidation, Nox4 and cellular adhesion molecule (CAM expression, ROS generation and leukocyte adhesion. Moreover, dermal microvascular endothelial cell dysfunction was prevented by Nox4 inhibition. Interestingly, inhibition of β-oxidation counteracted the beneficial effects of PLC on oxidative stress and endothelial dysfunction.PLC treatment improved rat skin flap viability, accelerated wound healing and dermal angiogenesis. The beneficial effects of PLC likely derived from improvement of mitochondrial β-oxidation and reduction of Nox4-mediated oxidative stress and endothelial dysfunction. Antioxidant therapy and

  9. Associative Interactions in Crowded Solutions of Biopolymers Counteract Depletion Effects.

    Science.gov (United States)

    Groen, Joost; Foschepoth, David; te Brinke, Esra; Boersma, Arnold J; Imamura, Hiromi; Rivas, Germán; Heus, Hans A; Huck, Wilhelm T S

    2015-10-14

    The cytosol of Escherichia coli is an extremely crowded environment, containing high concentrations of biopolymers which occupy 20-30% of the available volume. Such conditions are expected to yield depletion forces, which strongly promote macromolecular complexation. However, crowded macromolecule solutions, like the cytosol, are very prone to nonspecific associative interactions that can potentially counteract depletion. It remains unclear how the cytosol balances these opposing interactions. We used a FRET-based probe to systematically study depletion in vitro in different crowded environments, including a cytosolic mimic, E. coli lysate. We also studied bundle formation of FtsZ protofilaments under identical crowded conditions as a probe for depletion interactions at much larger overlap volumes of the probe molecule. The FRET probe showed a more compact conformation in synthetic crowding agents, suggesting strong depletion interactions. However, depletion was completely negated in cell lysate and other protein crowding agents, where the FRET probe even occupied slightly more volume. In contrast, bundle formation of FtsZ protofilaments proceeded as readily in E. coli lysate and other protein solutions as in synthetic crowding agents. Our experimental results and model suggest that, in crowded biopolymer solutions, associative interactions counterbalance depletion forces for small macromolecules. Furthermore, the net effects of macromolecular crowding will be dependent on both the size of the macromolecule and its associative interactions with the crowded background.

  10. Retrieval and sleep both counteract the forgetting of spatial information.

    Science.gov (United States)

    Antony, James W; Paller, Ken A

    2018-06-01

    Repeatedly studying information is a good way to strengthen memory storage. Nevertheless, testing recall often produces superior long-term retention. Demonstrations of this testing effect, typically with verbal stimuli, have shown that repeated retrieval through testing reduces forgetting. Sleep also benefits memory storage, perhaps through repeated retrieval as well. That is, memories may generally be subject to forgetting that can be counteracted when memories become reactivated, and there are several types of reactivation: (i) via intentional restudying, (ii) via testing, (iii) without provocation during wake, or (iv) during sleep. We thus measured forgetting for spatial material subjected to repeated study or repeated testing followed by retention intervals with sleep versus wake. Four groups of subjects learned a set of visual object-location associations and either restudied the associations or recalled locations given the objects as cues. We found the advantage for restudied over retested information was greater in the PM than AM group. Additional groups tested at 5-min and 1-wk retention intervals confirmed previous findings of greater relative benefits for restudying in the short-term and for retesting in the long-term. Results overall support the conclusion that repeated reactivation through testing or sleeping stabilizes information against forgetting. © 2018 Antony and Paller; Published by Cold Spring Harbor Laboratory Press.

  11. Subarray-based FDA radar to counteract deceptive ECM signals

    Science.gov (United States)

    Abdalla, Ahmed; Wang, Wen-Qin; Yuan, Zhao; Mohamed, Suhad; Bin, Tang

    2016-12-01

    In recent years, the frequency diverse array (FDA) radar concept has attracted extensive attention, as it may benefit from a small frequency increment, compared to the carrier frequency across the array elements and thereby achieve an array factor that is a function of the angle, the time, and the range which is superior to the conventional phase array radar (PAR). However, limited effort on the subject of FDA in electronic countermeasure scenarios, especially in the presence of mainbeam deceptive jamming, has been published. Basic FDA is not desirable for anti-jamming applications, due to the range-angle coupling response of targets. In this paper, a novel method based on subarrayed FDA signal processing is proposed to counteract deceptive ECM signals. We divide the FDA array into multiple subarrays, each of which employs a distinct frequency increment. As a result, in the subarray-based FDA, the desired target can be distinguished at subarray level in joint range-angle-Doppler domain by utilizing the fact that the jammer generates false targets with the same ranges to each subarray without reparations. The performance assessment shows that the proposed solution is effective for deceptive ECM targets suppression. The effectiveness is verified by simulation results.

  12. Counteracting structural errors in ensemble forecast of influenza outbreaks.

    Science.gov (United States)

    Pei, Sen; Shaman, Jeffrey

    2017-10-13

    For influenza forecasts generated using dynamical models, forecast inaccuracy is partly attributable to the nonlinear growth of error. As a consequence, quantification of the nonlinear error structure in current forecast models is needed so that this growth can be corrected and forecast skill improved. Here, we inspect the error growth of a compartmental influenza model and find that a robust error structure arises naturally from the nonlinear model dynamics. By counteracting these structural errors, diagnosed using error breeding, we develop a new forecast approach that combines dynamical error correction and statistical filtering techniques. In retrospective forecasts of historical influenza outbreaks for 95 US cities from 2003 to 2014, overall forecast accuracy for outbreak peak timing, peak intensity and attack rate, are substantially improved for predicted lead times up to 10 weeks. This error growth correction method can be generalized to improve the forecast accuracy of other infectious disease dynamical models.Inaccuracy of influenza forecasts based on dynamical models is partly due to nonlinear error growth. Here the authors address the error structure of a compartmental influenza model, and develop a new improved forecast approach combining dynamical error correction and statistical filtering techniques.

  13. Docosahexaenoic acid counteracts attenuation of CD95-induced cell death by inorganic mercury

    International Nuclear Information System (INIS)

    Gill, Randall; Lanni, Lydia; Jen, K.-L. Catherine; McCabe, Michael J.; Rosenspire, Allen

    2015-01-01

    In the United States the principal environmental exposure to mercury is through dietary consumption of sea food. Although the mechanism by which low levels of mercury affect the nervous system is not well established, epidemiological studies suggest that low level exposure of pregnant women to dietary mercury can adversely impact cognitive development in their children, but that Docosahexaenoic acid (DHA), the most prominent n-polyunsaturated fatty acid (n-PUFA) present in fish may counteract negative effects of mercury on the nervous system. Aside from effects on the nervous system, epidemiological and animal studies have also suggested that low level mercury exposure may be a risk factor for autoimmune disease. However unlike the nervous system where a mechanism linking mercury to impaired cognitive development remains elusive, we have previously suggested a potential mechanism linking low level mercury exposures to immune system dysfunction and autoimmunity. In the immune system it is well established that disruption of CD95 mediated apoptosis leads to autoimmune disease. We have previously shown in vitro as well as in vivo that in lymphocytes burdened with low levels of mercury, CD95 mediated cell death is impaired. In this report we now show that DHA counteracts the negative effect of mercury on CD95 signaling in T lymphocytes. T cells which have been pre-exposed to DHA are able to cleave pro-caspase 3 and efficiently signal programmed cell death through the CD95 signaling pathway, whether or not they are burdened with low levels of mercury. Thus DHA may lower the risk of autoimmune disease after low level mercury exposures. - Highlights: • Inorganic mercury (Hg 2+ ) interferes with CD95 mediated cell death in Jurkat T cells • DHA restores the ability of CD95 to signal cell death in Hg 2+ intoxicated T cells • The restoration of CD95 mediated cell death by DHA is correlated with increased activation of Caspase 3

  14. Docosahexaenoic acid counteracts attenuation of CD95-induced cell death by inorganic mercury

    Energy Technology Data Exchange (ETDEWEB)

    Gill, Randall [Department of Immunology and Microbiology, Wayne State University, Detroit MI (United States); Lanni, Lydia; Jen, K.-L. Catherine [Department of Nutrition and Food Science, Wayne State University, Detroit MI (United States); McCabe, Michael J. [Department of Environmental Medicine, University of Rochester, Rochester NY (United States); Rosenspire, Allen, E-mail: arosenspire@wayne.edu [Department of Immunology and Microbiology, Wayne State University, Detroit MI (United States)

    2015-01-01

    In the United States the principal environmental exposure to mercury is through dietary consumption of sea food. Although the mechanism by which low levels of mercury affect the nervous system is not well established, epidemiological studies suggest that low level exposure of pregnant women to dietary mercury can adversely impact cognitive development in their children, but that Docosahexaenoic acid (DHA), the most prominent n-polyunsaturated fatty acid (n-PUFA) present in fish may counteract negative effects of mercury on the nervous system. Aside from effects on the nervous system, epidemiological and animal studies have also suggested that low level mercury exposure may be a risk factor for autoimmune disease. However unlike the nervous system where a mechanism linking mercury to impaired cognitive development remains elusive, we have previously suggested a potential mechanism linking low level mercury exposures to immune system dysfunction and autoimmunity. In the immune system it is well established that disruption of CD95 mediated apoptosis leads to autoimmune disease. We have previously shown in vitro as well as in vivo that in lymphocytes burdened with low levels of mercury, CD95 mediated cell death is impaired. In this report we now show that DHA counteracts the negative effect of mercury on CD95 signaling in T lymphocytes. T cells which have been pre-exposed to DHA are able to cleave pro-caspase 3 and efficiently signal programmed cell death through the CD95 signaling pathway, whether or not they are burdened with low levels of mercury. Thus DHA may lower the risk of autoimmune disease after low level mercury exposures. - Highlights: • Inorganic mercury (Hg{sup 2+}) interferes with CD95 mediated cell death in Jurkat T cells • DHA restores the ability of CD95 to signal cell death in Hg{sup 2+} intoxicated T cells • The restoration of CD95 mediated cell death by DHA is correlated with increased activation of Caspase 3.

  15. The characteristics of the pediatric model for counteracting obesity in Serbia

    Directory of Open Access Journals (Sweden)

    Banićević Miloš

    2012-01-01

    Full Text Available Basic data on the establishment, features and results of the health care system for children and adolescents in the Republic of Serbia during the period 1950-1990 are given in the introductory remarks. Enormous pressure for the change of the health sector ownership and the profile of physicians in the primary pediatric care in the last decade of 20th century and at the beginning of 21st century is also emphasized. The destructive consequences of the sanctions of international community (1992-1995, NATO aggression (1999 and the change of the political system in Serbia (2000 caused the huge loss of gross domestic product, increase of the unemployment and poverty rates, and the decrease of the health expenditure rate to unsustainable levels (200-300 USD per capita. In spite of all misfortunes, Pediatric Association of Serbia, in response to the global obesity epidemic, offered in 2007 to the Ministry of health and the National Institute for health insurance the Project 'The prevention and treatment of obesity in children and adolescents in Serbia', as the pediatric chapter for future National strategy for counteracting obesity. The Project, ie the pediatric model for counteracting obesity is funded on the features of the health care system for children and adolescents in our country. The solidarity of the society and the continuous education of health care workers, adolescents and their parents about the significance of obesity epidemic are, in our conviction, key factors for the strengthening of adolescent's conscience on individual responsibility for own health as the prerequisite for successful control of obesity epidemic in adolescents.

  16. Webinar Presentation: Vitamins, Minerals and Metals: Do Healthy Diets Counteract Health Effects of Toxicants?

    Science.gov (United States)

    This presentation, Vitamins, Minerals and Metals: Do Healthy Diets Counteract Health Effects of Toxicants?, was given at the NIEHS/EPA Children's Centers 2015 Webinar Series: Food and Children's Health held on Dec. 9, 2015.

  17. Improvement of the organizational support of prevention and counteraction of corruption in the bodies of State Fiscal Service of Ukraine

    Directory of Open Access Journals (Sweden)

    S. M. Ivasenko

    2014-11-01

    Full Text Available The article analyses directions of perfection of organizational support of prevention and counteraction of corruption in the bodies of State fiscal service of Ukraine. It is noted that fight against corruption in tax authorities is the most important component of increasing the efficiency of tax administration and tax crime reducing. In its importance it can be equated to such important problems as the fighting against tax crimes. The author, generalizing theoretical approaches, highlights priority activities aimed at improving the efficiency of detecting and exposing corrupt employees of the fiscal authorities.

  18. Counteracting 16-QAM Optical Fiber Transmission Impairments With Iterative Turbo Equalization

    DEFF Research Database (Denmark)

    Arlunno, Valeria; Caballero Jambrina, Antonio; Borkowski, Robert

    2013-01-01

    A turbo equalization (TE) scheme based on convolutional code and normalized least mean square equalizer for coherent optical communication links is proposed and experimentally demonstrated. The proposed iterative TE technique is proved effective for counteracting polarization-division-multiplexin......A turbo equalization (TE) scheme based on convolutional code and normalized least mean square equalizer for coherent optical communication links is proposed and experimentally demonstrated. The proposed iterative TE technique is proved effective for counteracting polarization...

  19. Lactoferrin Efficiently Counteracts the Inflammation-Induced Changes of the Iron Homeostasis System in Macrophages.

    Science.gov (United States)

    Cutone, Antimo; Rosa, Luigi; Lepanto, Maria Stefania; Scotti, Mellani Jinnett; Berlutti, Francesca; Bonaccorsi di Patti, Maria Carmela; Musci, Giovanni; Valenti, Piera

    2017-01-01

    Human lactoferrin (hLf), an 80-kDa multifunctional iron-binding cationic glycoprotein, is constitutively secreted by exocrine glands and by neutrophils during inflammation. hLf is recognized as a key element in the host immune defense system. The in vitro and in vivo experiments are carried out with bovine Lf (bLf), which shares high sequence homology and identical functions with hLf, including anti-inflammatory activity. Here, in "pure" M1 human macrophages, obtained by stimulation with a mixture of 10 pg/ml LPS and 20 ng/ml IFN-γ, as well as in a more heterogeneous macrophage population, challenged with high-dose of LPS (1 µg/ml), the effect of bLf on the expression of the main proteins involved in iron and inflammatory homeostasis, namely ferroportin (Fpn), membrane-bound ceruloplasmin (Cp), cytosolic ferritin (Ftn), transferrin receptor 1, and cytokines has been investigated. The increase of IL-6 and IL-1β cytokines, following the inflammatory treatments, is associated with both upregulation of cytosolic Ftn and downregulation of Fpn, membrane-bound Cp, and transferrin receptor 1. All these changes take part into intracellular iron overload, a very unsafe condition leading in vivo to higher host susceptibility to infections as well as iron deficiency in the blood and anemia of inflammation. It is, therefore, of utmost importance to counteract the persistence of the inflammatory status to rebalance iron levels between tissues/secretions and blood. Moreover, levels of the antiinflammatory cytokine IL-10 were increased in cells treated with high doses of LPS. Conversely, IL-10 decreased when the LPS/IFN-γ mix was used, suggesting that only the inflammation triggered by LPS high doses can switch on an anti-inflammatory response in our macrophagic model. Here, we demonstrate that bLf, when included in the culture medium, significantly reduced IL-6 and IL-1β production and efficiently prevented the changes of Fpn, membrane-bound Cp, cytosolic Ftn, and

  20. Lactoferrin Efficiently Counteracts the Inflammation-Induced Changes of the Iron Homeostasis System in Macrophages

    Directory of Open Access Journals (Sweden)

    Antimo Cutone

    2017-06-01

    Full Text Available Human lactoferrin (hLf, an 80-kDa multifunctional iron-binding cationic glycoprotein, is constitutively secreted by exocrine glands and by neutrophils during inflammation. hLf is recognized as a key element in the host immune defense system. The in vitro and in vivo experiments are carried out with bovine Lf (bLf, which shares high sequence homology and identical functions with hLf, including anti-inflammatory activity. Here, in “pure” M1 human macrophages, obtained by stimulation with a mixture of 10 pg/ml LPS and 20 ng/ml IFN-γ, as well as in a more heterogeneous macrophage population, challenged with high-dose of LPS (1 µg/ml, the effect of bLf on the expression of the main proteins involved in iron and inflammatory homeostasis, namely ferroportin (Fpn, membrane-bound ceruloplasmin (Cp, cytosolic ferritin (Ftn, transferrin receptor 1, and cytokines has been investigated. The increase of IL-6 and IL-1β cytokines, following the inflammatory treatments, is associated with both upregulation of cytosolic Ftn and downregulation of Fpn, membrane-bound Cp, and transferrin receptor 1. All these changes take part into intracellular iron overload, a very unsafe condition leading in vivo to higher host susceptibility to infections as well as iron deficiency in the blood and anemia of inflammation. It is, therefore, of utmost importance to counteract the persistence of the inflammatory status to rebalance iron levels between tissues/secretions and blood. Moreover, levels of the antiinflammatory cytokine IL-10 were increased in cells treated with high doses of LPS. Conversely, IL-10 decreased when the LPS/IFN-γ mix was used, suggesting that only the inflammation triggered by LPS high doses can switch on an anti-inflammatory response in our macrophagic model. Here, we demonstrate that bLf, when included in the culture medium, significantly reduced IL-6 and IL-1β production and efficiently prevented the changes of Fpn, membrane-bound Cp

  1. Green tea (-)-epigallocatechin-3-gallate counteracts daytime overeating induced by high-fat diet in mice.

    Science.gov (United States)

    Li, Hongyu; Kek, Huiling Calvina; Lim, Joy; Gelling, Richard Wayne; Han, Weiping

    2016-12-01

    High-fat diet (HFD) induces overeating and obesity. Green tea (-)-epigallocatechin-3-gallate (EGCG) reduces HFD-induced body weight and body fat gain mainly through increased lipid metabolism and fat oxidation. However, little is known about its effect on HFD-induced alterations in feeding behavior. Three diet groups of wildtype C57B/6j male mice at 5 months old were fed on normal chow diet, 1 week of HFD (60% of energy) and 3 months of HFD (diet-induced obesity (DIO)) prior to EGCG supplement in respective diet. EGCG had no effect on feeding behavior in normal chow diet group. Increased daytime feeding induced by HFD was selectively corrected by EGCG treatment in HFD groups, including reversed food intake, feeding frequency and meal size in HFD + EGCG group, and reduced food intake and feeding frequency in DIO + EGCG group. Moreover, EGCG treatment altered diurnally oscillating expression pattern of key appetite-regulating genes, including AGRP, POMC, and CART, and key circadian genes Clock and Bmal1 in hypothalamus of DIO mice, indicating its central effect on feeding regulation. Our study demonstrates that EGCG supplement specifically counteracts daytime overeating induced by HFD in mice, suggesting its central role in regulating feeding behavior and energy homeostasis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Evidence That the Microbiota Counteracts Male Outbreeding Strategy by Inhibiting Sexual Signaling in Females

    Directory of Open Access Journals (Sweden)

    Chloe Heys

    2018-03-01

    Full Text Available The microbiota is increasingly being recognized as having important impacts on many host biological processes. However, evidence of its effects on animal communication and breeding strategy is lacking. In this three-factorial study, we show that females were more willing to mate with related males, with relatedness likely being assessed through the microbiota. By contrast, male mating investment is concurrently determined by both the relatedness and microbiota status of the female. When the microbiota in female Drosophila melanogaster is altered by an antibiotic, male investment in sperm number increased when mating with unrelated females compared to related ones. Contrastingly, the presence of an intact microbiota in females canceled this male outbreeding strategy. As a consequence, the microbiota, when intact, decreased the fitness of the mating couple. Furthermore, we showed that female sexual signaling (cuticular hydrocarbons, with regards to kin recognition, significantly interacts with microbiota. Interestingly, the interaction is significant for hydrocarbons expressed by both sexes, but not for female-specific compounds. Taken together, our results suggest that microbiota can influence kin recognition by disfavoring male outbreeding strategies, likely by inhibiting key olfactory sexual signaling. This represents the first evidence of a host outbreeding strategy counteracted by their microbiota.

  3. Anthocyanin-rich extract from Hibiscus sabdariffa calyx counteracts UVC-caused impairments in rats.

    Science.gov (United States)

    Ozkol, Hatice Uce; Koyuncu, Ismail; Tuluce, Yasin; Dilsiz, Nihat; Soral, Sinan; Ozkol, Halil

    2015-01-01

    Ultraviolet radiation (UV) was reported to cause oxidative stress. Hibiscus sabdariffa L. (Malvaceae) calyx is commonly used in traditional Asian and African medicines and possesses strong antioxidant capacity due to its anthocyanin (ANTH) content. This study researched the possible protective role of Hibiscus sabdariffa calyx extract (HSCE) in UVC exposure of rats. Levels of serum enzymes, renal function tests, and some oxidant/antioxidant biomarkers of skin, lens, and retina tissues were monitored. Rats were exposed to UVC 4 h daily for 40 d and simultaneously received HSCE containing 2.5, 5, and 10 mg doses of ANTH in drinking water. Significant (p < 0.05) increases in the levels of serum aminotransferases, lactate dehydrogenase, urea, creatinine, and uric acid were noted after UVC exposure. In skin, lens, and retina tissues, total oxidant status, oxidative stress index, lipid peroxidation, and protein oxidation escalated markedly (p < 0.05) whereas total antioxidant status, reduced glutathione, and superoxide dismutase decreased dramatically (p < 0.05) related to UVC. Co-administration of HSCE with each ANTH dose significantly (p < 0.05) reversed aforementioned parameters (except total oxidant status) almost in all tissues. The LD50 of HSCE in rats was determined to be above 5000 mg/kg. Our data revealed that HSCE has a remarkable potential to counteract UVC-caused impairments, probably through its antioxidant and free radical-defusing effects. Therefore, HSCE could be useful against some cutaneous and ocular diseases in which UV and oxidative stress have a role in the etiopathogenesis.

  4. Exendin-4 induces cell adhesion and differentiation and counteracts the invasive potential of human neuroblastoma cells.

    Science.gov (United States)

    Luciani, Paola; Deledda, Cristiana; Benvenuti, Susanna; Squecco, Roberta; Cellai, Ilaria; Fibbi, Benedetta; Marone, Ilaria Maddalena; Giuliani, Corinna; Modi, Giulia; Francini, Fabio; Vannelli, Gabriella Barbara; Peri, Alessandro

    2013-01-01

    Exendin-4 is a molecule currently used, in its synthetic form exenatide, for the treatment of type 2 diabetes mellitus. Exendin-4 binds and activates the Glucagon-Like Peptide-1 Receptor (GLP-1R), thus inducing insulin release. More recently, additional biological properties have been associated to molecules that belong to the GLP-1 family. For instance, Peptide YY and Vasoactive Intestinal Peptide have been found to affect cell adhesion and migration and our previous data have shown a considerable actin cytoskeleton rearrangement after exendin-4 treatment. However, no data are currently available on the effects of exendin-4 on tumor cell motility. The aim of this study was to investigate the effects of this molecule on cell adhesion, differentiation and migration in two neuroblastoma cell lines, SH-SY5Y and SK-N-AS. We first demonstrated, by Extra Cellular Matrix cell adhesion arrays, that exendin-4 increased cell adhesion, in particular on a vitronectin substrate. Subsequently, we found that this molecule induced a more differentiated phenotype, as assessed by i) the evaluation of neurite-like protrusions in 3D cell cultures, ii) the analysis of the expression of neuronal markers and iii) electrophysiological studies. Furthermore, we demonstrated that exendin-4 reduced cell migration and counteracted anchorage-independent growth in neuroblastoma cells. Overall, these data indicate for the first time that exendin-4 may have anti-tumoral properties.

  5. Feebates promoting energy-efficient cars: Design options to address more consumers and possible counteracting effects

    International Nuclear Information System (INIS)

    Peters, Anja; Mueller, Michel G.; Haan, Peter de; Scholz, Roland W.

    2008-01-01

    An increasing number of countries have implemented or are evaluating feebate systems in order to reduce energy consumption of new vehicle registrations. We distinguish between absolute feebates based strictly on a vehicle's energy consumption and relative feebates normalizing energy consumption by a given car utility. This paper analyzes whether absolute or relative feebates encourage more consumers to change to vehicles with lower energy consumption. We combine an analysis of all car models on sale at the end of 2005 with survey data from 326 potential new car buyers. Analysis of the car fleet with regard to behavioral changes assumed as realistic shows that relative systems succeed better in offering more consumer groups cars that are eligible for incentives. Survey results suggest that consumers show some, but limited, willingness to change behavior to obtain an incentive. However, a relative system potentially allows people to switch to cars with higher relative efficiency without actually lowering absolute CO 2 emissions. We discuss this inherent dilemma of simultaneously addressing more consumers and limiting counteracting effects. In order to find the optimal trade-off, we suggest assessing different parameters operationalizing vehicle utility by means of micro-simulation with detailed car fleet and differentiated consumer segments

  6. Selenium-Induced Toxicity Is Counteracted by Sulfur in Broccoli (Brassica oleracea L. var. italica).

    Science.gov (United States)

    Tian, Ming; Hui, Maixia; Thannhauser, Theodore W; Pan, Siyi; Li, Li

    2017-01-01

    Selenium (Se) is an essential micronutrient for humans. Increasing Se content in food crops offers an effective approach to enhance the consumption of Se in human diets. A thoroughly understanding of the effects of Se on plant growth is important for Se biofortification in food crops. Given that Se is an analog of sulfur (S) and can be toxic to plants, its effect on plant growth is expected to be greatly affected by S nutrition. However, this remains to be further understood. Here, we evaluated the influence of Se treatments on broccoli ( Brassica oleracea L. var. italica ) growth when S was withheld from the growth nutrient solution. We found that Se was highly toxic to plants when S nutrition was poor. In contrast to Se treatments with adequate S nutrition that slightly reduced broccoli growth, the same concentration of Se treatments without S supplementation dramatically reduced plant sizes. Higher Se toxicity was observed with selenate than selenite under low S nutrition. We examined the bases underlying the toxicity. We discovered that the high Se toxicity in low S nutrition was specifically associated with an increased ratio of Se in proteins verse total Se level, enhanced generation of reactive oxygen species, elevated lipid peroxidation causing increased cell membrane damage, and reduced antioxidant enzyme activities. Se toxicity could be counteracted with increased supplementation of S, which is likely through decreasing non-specific integration of Se into proteins and altering the redox system. The present study provides information for better understanding of Se toxicity and shows that adequate S nutrition is important to prevent Se toxicity during biofortification of crops by Se fertilization.

  7. Selenium-Induced Toxicity Is Counteracted by Sulfur in Broccoli (Brassica oleracea L. var. italica

    Directory of Open Access Journals (Sweden)

    Ming Tian

    2017-08-01

    Full Text Available Selenium (Se is an essential micronutrient for humans. Increasing Se content in food crops offers an effective approach to enhance the consumption of Se in human diets. A thoroughly understanding of the effects of Se on plant growth is important for Se biofortification in food crops. Given that Se is an analog of sulfur (S and can be toxic to plants, its effect on plant growth is expected to be greatly affected by S nutrition. However, this remains to be further understood. Here, we evaluated the influence of Se treatments on broccoli (Brassica oleracea L. var. italica growth when S was withheld from the growth nutrient solution. We found that Se was highly toxic to plants when S nutrition was poor. In contrast to Se treatments with adequate S nutrition that slightly reduced broccoli growth, the same concentration of Se treatments without S supplementation dramatically reduced plant sizes. Higher Se toxicity was observed with selenate than selenite under low S nutrition. We examined the bases underlying the toxicity. We discovered that the high Se toxicity in low S nutrition was specifically associated with an increased ratio of Se in proteins verse total Se level, enhanced generation of reactive oxygen species, elevated lipid peroxidation causing increased cell membrane damage, and reduced antioxidant enzyme activities. Se toxicity could be counteracted with increased supplementation of S, which is likely through decreasing non-specific integration of Se into proteins and altering the redox system. The present study provides information for better understanding of Se toxicity and shows that adequate S nutrition is important to prevent Se toxicity during biofortification of crops by Se fertilization.

  8. MECHANISMS OF COUNTERACTING FLAP-VALVE BRONCHIAL OBSTRUCTION IN CASE OF OBSTRUCTIVE PULMONARY EMPHYSEMA

    Directory of Open Access Journals (Sweden)

    K. F. Tetenev

    2015-01-01

    Full Text Available The research goal was to formulate and substantiate the hypothesis explaining support for an expiratory air flow in case of pulmonary emphysema. The research method consisted in comparing the mechanical properties of lungs in practically healthy individuals (37 individuals, mean age – (30.4 ± 1.7 y.o. and COPD patients with pronounced lung emphysema (30 patients, mean age – (52.1 ± 2.3 y.o. as well as those of isolated normal lungs (n = 14 and isolated lungs of patients who died of COPD (n = 5. Pulmo-nary mechanics was studied via the simultaneous measurement of transpulmonary pressure and lung ven-tilation volume. General lung hysteresis and elastic lung hysteresis were calculated. The mechanical properties of isolated lungs were studied using passive ventilation under the Donders bell. The air flow was interrupted in order to measure alveolar pressure and develop an elastic lung hysteresis curve. Pres-sure in the Donders bell was changed by means of a special pump in automatic and manual modes. The research has not revealed any fundamental differences between the mechanical properties of the normal and emphysematous lungs. A minimum increase in the pressure inside the Donders bell over atmospheric pressure used to stop air ejection in both normal and the emphysematous lungs as the result of flap-valve bronchial obstruction. In living beings, air is ejected from lungs with an increase in pressure under the conditions of forced expiration. Pressure increases up to (38.6 ± 2.71 cm H2O in healthy individuals and up to (20.5 ± 1.86 cm H2O in COPD patients. Probably, an expiratory air flow is supported by active expiratory bronchial dilatation that counteracts flap-valve bronchial obstruction. The hypothesis is based on the confirmed ability of the lungs to perform inspiratory actions (in addition to the action of respiratory muscles and the theory of mechanical lung activity.

  9. Housing in Pyramid Counteracts Neuroendocrine and Oxidative Stress Caused by Chronic Restraint in Rats

    Directory of Open Access Journals (Sweden)

    M. Surekha Bhat

    2007-01-01

    Full Text Available The space within the great pyramid and its smaller replicas is believed to have an antistress effect. Research has shown that the energy field within the pyramid can protect the hippocampal neurons of mice from stress-induced atrophy and also reduce neuroendocrine stress, oxidative stress and increase antioxidant defence in rats. In this study, we have, for the first time, attempted to study the antistress effects of pyramid exposure on the status of cortisol level, oxidative damage and antioxidant status in rats during chronic restraint stress. Adult female Wistar rats were divided into four groups as follows: normal controls (NC housed in home cage and left in the laboratory; restrained rats (with three subgroups subject to chronic restraint stress by placing in a wire mesh restrainer for 6 h per day for 14 days, the restrained controls (RC having their restrainers kept in the laboratory; restrained pyramid rats (RP being kept in the pyramid; and restrained square box rats (RS in the square box during the period of restraint stress everyday. Erythrocyte malondialdehyde (MDA and plasma cortisol levels were significantly increased and erythrocyte-reduced glutathione (GSH levels, erythrocyte glutathione peroxidase (GSH-Px and superoxide dismutase (SOD activities were significantly decreased in RC and RS rats as compared to NC. However, these parameters were maintained to near normal levels in RP rats which showed significantly decreased erythrocyte MDA and plasma cortisol and significantly increased erythrocyte GSH levels, erythrocyte GSH-Px and SOD activities when compared with RS rats. The results showed that housing in pyramid counteracts neuroendocrine and oxidative stress caused by chronic restraint in rats.

  10. Effects of counteracting external valgus moment on lateral tibial cartilage contact conditions and tibial rotation.

    Science.gov (United States)

    Shriram, Duraisamy; Parween, Rizuwana; Lee, Yee Han Dave; Subburaj, Karupppasamy

    2017-07-01

    Knee osteoarthritis that prevalently occurs at the medial compartment is a progressive chronic disorder affecting the articular cartilage of the knee joint, and lead to loss of joint functionality. Valgus braces have been used as a treatment procedure to unload the medial compartment for patients with medial osteoarthritis. Valgus braces through the application of counteracting external valgus moment shift the load from medial compartment towards the lateral compartment. Previous biomechanical studies focused only on the changes in varus moments before and after wearing the brace. The objective of this study was to investigate the influence of opposing external valgus moment applied by knee braces on the lateral tibial cartilage contact conditions using a 3D finite element model of the knee joint. Finite element simulations were performed on the knee joint model without and with the application of opposing valgus moment to mimic the unbraced and braced conditions. Lateral tibial cartilage contact pressures and contact area, and tibial rotation (varus-valgus and internal-external) were estimated for the complete walking gait cycle. The opposing valgus moment increased the maximum contact pressure and contact area on the lateral tibial cartilage compared to the normal gait moment. A peak contact pressure of 8.2 MPa and maximum cartilage loaded area of 28% (loaded cartilage nodes) on the lateral cartilage with the application of external valgus moment were induced at 50% of the gait cycle. The results show that the use of opposing valgus moment may significantly increase the maximum contact pressures and contact area on the lateral tibial cartilage and increases the risk of articular cartilage damage on the lateral compartment.

  11. Candida utilis and Chlorella vulgaris counteract intestinal inflammation in Atlantic salmon (Salmo salar L..

    Directory of Open Access Journals (Sweden)

    Fabian Grammes

    Full Text Available Intestinal inflammation, caused by impaired intestinal homeostasis, is a serious condition in both animals and humans. The use of conventional extracted soybean meal (SBM in diets for Atlantic salmon and several other fish species is known to induce enteropathy in the distal intestine, a condition often referred to as SBM induced enteropathy (SBMIE. In the present study, we investigated the potential of different microbial ingredients to alleviate SBMIE in Atlantic salmon, as a model of feed-induced inflammation. The dietary treatments consisted of a negative control based on fish meal (FM, a positive control based on 20% SBM, and four experimental diets combining 20% SBM with either one of the three yeasts Candida utilis (CU, Kluyveromyces marxianus (KM, Saccharomyces cerevisiae (SC or the microalgae Chlorella vulgaris (CV. Histopathological examination of the distal intestine showed that all fish fed the SC or SBM diets developed characteristic signs of SBMIE, while those fed the FM, CV or CU diets showed a healthy intestine. Fish fed the KM diet showed intermediate signs of SBMIE. Corroborating results were obtained when measuring the relative length of PCNA positive cells in the crypts of the distal intestine. Gene set enrichment analysis revealed decreased expression of amino acid, fat and drug metabolism pathways as well as increased expression of the pathways for NOD-like receptor signalling and chemokine signalling in both the SC and SBM groups while CV and CU were similar to FM and KM was intermediate. Gene expression of antimicrobial peptides was reduced in the groups showing SBMIE. The characterisation of microbial communities using PCR-DGGE showed a relative increased abundance of Firmicutes bacteria in fish fed the SC or SBM diets. Overall, our results show that both CU and CV were highly effective to counteract SBMIE, while KM had less effect and SC had no functional effects.

  12. Renewable Energy Production from Waste to Mitigate Climate Change and Counteract Soil Degradation - A Spatial Explicit Assessment for Japan

    Science.gov (United States)

    Kraxner, Florian; Yoshikawa, Kunio; Leduc, Sylvain; Fuss, Sabine; Aoki, Kentaro; Yamagata, Yoshiki

    2014-05-01

    Waste production from urban areas is growing faster than urbanization itself, while at the same time urban areas are increasingly contributing substantial emissions causing climate change. Estimates indicate for urban residents a per capita solid waste (MSW) production of 1.2 kg per day, subject to further increase to 1.5 kg beyond 2025. Waste water and sewage production is estimated at about 260 liters per capita and day, also at increasing rates. Based on these figures, waste - including e.g. MSW, sewage and animal manure - can generally be assumed as a renewable resource with varying organic components and quantity. This paper demonstrates how new and innovative technologies in the field of Waste-to-Green Products can help in various ways not only to reduce costs for waste treatment, reduce the pressure on largely overloaded dump sites, and reduce also the effect of toxic materials at the landfill site and by that i.e. protect the groundwater. Moreover, Waste-to-Green Products can contribute actively to mitigating climate change through fossil fuel substitution and carbon sequestration while at the same time counteracting negative land use effects from other types of renewable energy and feedstock production through substitution. At the same time, the co-production and recycling of fertilizing elements and biochar can substantially counteract soil degradation and improve the soil organic carbon content of different land use types. The overall objective of this paper is to assess the total climate change mitigation potential of MSW, sewage and animal manure for Japan. A techno-economic approach is used to inform the policy discussion on the suitability of this substantial and sustainable mitigation option. We examine the spatial explicit technical mitigation potential from e.g. energy substitution and carbon sequestration through biochar in rural and urban Japan. For this exercise, processed information on respective Japanese waste production, energy demand

  13. A Case for Relational Leadership and an Ethics of Care for Counteracting Bullying at Schools

    Science.gov (United States)

    Smit, Brigitte; Scherman, Vanessa

    2016-01-01

    This paper attends to a theoretical exposition of relational leadership and ethics care as complementary approaches to educational leadership in counteracting bullying at schools. Schools constitute complex systems of activities, processes and dynamics. More specifically, a social system in schools is a web of interactions between the various…

  14. Dialogue and Exchange of Information about Grade Inflation Can Counteract Its Effects

    Science.gov (United States)

    Barriga, Alvaro Q.; Cooper, Eric K.; Gawelek, Mary Ann; Butela, Kristin; Johnson, Elizabeth

    2008-01-01

    This investigation documents an intervention that successfully counteracted a grade inflation trend at a small, Catholic, liberal arts university in the eastern United States. The intervention produced a significant drop in grades awarded by full-time faculty, but not by adjunct faculty who were not yet included in the intervention. Institutional…

  15. Maldistribution in air-water heat pump evaporators. Part 2: Economic analysis of counteracting technologies

    DEFF Research Database (Denmark)

    Mader, Gunda; Palm, Björn; Elmegaard, Brian

    2015-01-01

    maldistribution,high electricity prices, and colder climate. Investment in the individual superheat controltechnology, however, can be quickly amortized in many scenarios. For the warmer climatezone with a small number of operating hours counteracting of maldistribution does notpay off under the used economic...... assumptions.© 2014 Elsevier Ltd and IIR. All rights reserved....

  16. Alanine Counteracts the Destabilizing Effect that Urea has on RNase-A.

    Science.gov (United States)

    Chowhan, Rimpy K; Ali, Fasil; Bhat, Mohd Y; Rahman, Safikur; Singh, Laishram R; Ahmad, Faizan; Dar, Tanveer A

    2016-01-01

    It is generally believed that organisms use and accumulate methylamine osmolytes to prevent urea's damaging effect on protein stability and activity. However, urea-rich cells not only accumulate methylamines but also many other methylated and non-methylated compounds as well. But, so far it is not known whether osmolytes that are not accumulated in urea-rich cells could also confer urea-counteracting properties. We investigated the behavior of a non-methylamine osmolyte, alanine for its counteracting effect against urea denaturation of a model protein, ribonuclease A (RNase-A). We have measured structure and thermodynamic parameters (Tm, ΔHm, and ΔGD°) of RNase-A in the presence of alanine, urea and their combination. The results were also compared with the ability of glycine (osmolyte lacking one methyl group when compared with alanine) to counter urea's effect on protein stability. We observed that alanine but not glycine counteracts urea's harmful effect on RNase-A stability. The results indicated that alanine (in addition to methylamine osmolytes) may serve as an alternate urea-counteractant. Since glycine fails to protect RNase-A from urea's destabilizing effect, it seems that methylation to glycine might have some evolutionary significance to protect proteins against harmful effects of urea.

  17. Counteracting media’s thin body ideal in adolescent girls: informing is more effective than warning.

    NARCIS (Netherlands)

    Veldhuis, J.; Konijn, E.A.; Seidell, J.C.

    2014-01-01

    The present study investigated whether information or warnings about depictions of the thin-body ideal in mass media are effective in counteracting media-induced negative body perceptions of adolescent girls. Based on counter-advertising and reactance theories, our hypotheses were tested in a 3

  18. The condition of counteraction to administrative corruption offenses in state authorities and local government

    Directory of Open Access Journals (Sweden)

    О. В. Клок

    2014-12-01

    Full Text Available Article discusses questions dedicated to the analysis of the condition of counteraction to administrative corruption offenses in Ukraine. The statistical information on the dynamics, structure, specific gravity, cost and latency of the administrative corruption is researched. The most effective measures against corrupt practices at the state and municipal service are drawn.

  19. Borax counteracts genotoxicity of aluminum in rat liver.

    Science.gov (United States)

    Turkez, Hasan; Geyikoğlu, Fatime; Tatar, Abdulgani

    2013-10-01

    This study was carried out to evaluate the protective role of borax (BX) on genotoxicity induced by aluminum (Al) in rat liver, using liver micronucleus assay as an indicator of genotoxicity. Sprague-Dawley rats were randomly separated into six groups and each group had four animals. Aluminum chloride (AlCl₃; 5 mg/kg b.w.) and BX (3.25 and 13 mg/kg b.w.) were injected intraperitoneally to rats. Besides, animals were also treated with Al for 4 consecutive days followed by BX for 10 days. Rats were anesthetized after Al and BX injections and the hepatocytes were isolated for counting the number of micronucleated hepatocytes (MNHEPs). AlCl₃ was found to significantly (p < 0.05) increase the number of MNHEPs. Rats treated with BX, however, showed no increase in MNHEPs. Moreover, simultaneous treatments with BX significantly modulated the genotoxic effects of AlCl₃ in rats. It can be concluded that BX has beneficial influences and has the ability to antagonize Al toxicity.

  20. The N-end rule pathway counteracts cell death by destroying proapoptotic protein fragments.

    Science.gov (United States)

    Piatkov, Konstantin I; Brower, Christopher S; Varshavsky, Alexander

    2012-07-03

    In the course of apoptosis, activated caspases cleave ∼500 to ∼1,000 different proteins in a mammalian cell. The dynamics of apoptosis involve a number of previously identified, caspase-generated proapoptotic protein fragments, defined as those that increase the probability of apoptosis. In contrast to activated caspases, which can be counteracted by inhibitor of apoptosis proteins, there is little understanding of antiapoptotic responses to proapoptotic protein fragments. One possibility is the regulation of proapoptotic fragments through their selective degradation. The previously identified proapoptotic fragments Cys-RIPK1, Cys-TRAF1, Asp-BRCA1, Leu-LIMK1, Tyr-NEDD9, Arg-BID, Asp-BCL(XL), Arg-BIM(EL), Asp-EPHA4, and Tyr-MET bear destabilizing N-terminal residues. Tellingly, the destabilizing nature (but not necessarily the actual identity) of N-terminal residues of proapoptotic fragments was invariably conserved in evolution. Here, we show that these proapoptotic fragments are short-lived substrates of the Arg/N-end rule pathway. Metabolic stabilization of at least one such fragment, Cys-RIPK1, greatly augmented the activation of the apoptosis-inducing effector caspase-3. In agreement with this understanding, even a partial ablation of the Arg/N-end rule pathway in two specific N-end rule mutants is shown to sensitize cells to apoptosis. We also found that caspases can inactivate components of the Arg/N-end rule pathway, suggesting a mutual suppression between this pathway and proapoptotic signaling. Together, these results identify a mechanistically specific and functionally broad antiapoptotic role of the Arg/N-end rule pathway. In conjunction with other apoptosis-suppressing circuits, the Arg/N-end rule pathway contributes to thresholds that prevent a transient or otherwise weak proapoptotic signal from reaching the point of commitment to apoptosis.

  1. Exercise counteracts fatty liver disease in rats fed on fructose-rich diet

    Directory of Open Access Journals (Sweden)

    Voltarelli Fabrício A

    2010-10-01

    Full Text Available Abstract Background This study aimed to analyze the effects of exercise at the aerobic/anaerobic transition on the markers of non-alcoholic fatty liver disease (NAFLD, insulin sensitivity and the blood chemistry of rats kept on a fructose-rich diet. Methods We separated 48 Wistar rats into two groups according to diet: a control group (balanced diet AIN-93 G and a fructose-rich diet group (60% fructose. The animals were tested for maximal lactate-steady state (MLSS in order to identify the aerobic/anaerobic metabolic transition during swimming exercises at 28 and 90 days of age. One third of the animals of each group were submitted to swimming training at an intensity equivalent to the individual MLSS for 1 hours/day, 5 days/week from 28 to 120 days (early protocol. Another third were submitted to the training from 90 to 120 days (late protocol, and the others remained sedentary. The main assays performed included an insulin tolerance test (ITT and tests of serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST] activities, serum triglyceride concentrations [TG] and liver total lipid concentrations. Results The fructose-fed rats showed decreased insulin sensitivity, and the late-exercise training protocol counteracted this alteration. There was no difference between the groups in levels of serum ALT, whereas AST and liver lipids increased in the fructose-fed sedentary group when compared with the other groups. Serum triglycerides concentrations were higher in the fructose-fed trained groups when compared with the corresponding control group. Conclusions The late-training protocol was effective in restoring insulin sensitivity to acceptable standards. Considering the markers here evaluated, both training protocols were successful in preventing the emergence of non-alcoholic fatty liver status disease.

  2. The Use of gamma-Irradiation in Counteracting the Effect of Salinity for Cultivation of Barley and Pea Plants

    International Nuclear Information System (INIS)

    Aly, M.A.S.; Afifi, L.M.; Kamel, H.A.; Mostafa, I.Y.; Kord, M.A.

    2000-01-01

    The biochemical changes induced by salinity in two economic plants (Barley and Pea) and the probable counteraction of gamma irradiation for enhancement of growth were studied. The data obtained revealed that the reduction in pigments content due to salinity treatment was more pronounced in pea plants than barley. However, gamma irradiation caused a significant increase in pigment content of both plants. The interaction effect of salinity and radiation varied from an increase in case of barley to a reduction in peas. In both plants, soluble sugars content increased due to salinity and /or gamma-radiation. Moreover, total carbohydrates increased due to the combined treatment. A matched increase in free proline content was recorded with increase of salinity. While, gamma-irradiation showed a different trend. Protein and nucleic acids contents were proportionally decreased with increase of salinity levels, whereas gamma radiation induced an increase in both protein and nucleic acids content. A progressive reduction in the yield by increasing salinity was observed, while gamma-irradiation increased the yield of both plants. 14 CO 2 fixation was reduced by salinity treatment while gamma-radiation increased it. Contrary to 14 CO 2 fixation, salinity enhanced respiration, while radiation retarded it

  3. Gc-protein-derived macrophage activating factor counteracts the neuronal damage induced by oxaliplatin.

    Science.gov (United States)

    Morucci, Gabriele; Branca, Jacopo J V; Gulisano, Massimo; Ruggiero, Marco; Paternostro, Ferdinando; Pacini, Alessandra; Di Cesare Mannelli, Lorenzo; Pacini, Stefania

    2015-02-01

    Oxaliplatin-based regimens are effective in metastasized advanced cancers. However, a major limitation to their widespread use is represented by neurotoxicity that leads to peripheral neuropathy. In this study we evaluated the roles of a proven immunotherapeutic agent [Gc-protein-derived macrophage activating factor (GcMAF)] in preventing or decreasing oxaliplatin-induced neuronal damage and in modulating microglia activation following oxaliplatin-induced damage. The effects of oxaliplatin and of a commercially available formula of GcMAF [oleic acid-GcMAF (OA-GcMAF)] were studied in human neurons (SH-SY5Y cells) and in human microglial cells (C13NJ). Cell density, morphology and viability, as well as production of cAMP and expression of vascular endothelial growth factor (VEGF), markers of neuron regeneration [neuromodulin or growth associated protein-43 (Gap-43)] and markers of microglia activation [ionized calcium binding adaptor molecule 1 (Iba1) and B7-2], were determined. OA-GcMAF reverted the damage inflicted by oxaliplatin on human neurons and preserved their viability. The neuroprotective effect was accompanied by increased intracellular cAMP production, as well as by increased expression of VEGF and neuromodulin. OA-GcMAF did not revert the effects of oxaliplatin on microglial cell viability. However, it increased microglial activation following oxaliplatin-induced damage, resulting in an increased expression of the markers Iba1 and B7-2 without any concomitant increase in cell number. When neurons and microglial cells were co-cultured, the presence of OA-GcMAF significantly counteracted the toxic effects of oxaliplatin. Our results demonstrate that OA-GcMAF, already used in the immunotherapy of advanced cancers, may significantly contribute to neutralizing the neurotoxicity induced by oxaliplatin, at the same time possibly concurring to an integrated anticancer effect. The association between these two powerful anticancer molecules would probably produce

  4. Rostafuroxin: an ouabain-inhibitor counteracting specific forms of hypertension.

    Science.gov (United States)

    Ferrari, Patrizia

    2010-12-01

    An innovative approach to the therapy of essential hypertension (EH) and the related complications has been pursued by our group with the aim of defining specific genetic-molecular mechanisms underlying the disease in sub-sets of patients. This approach is anticipated to have a major effect on the clinical practice, diagnostics and development of new drugs able to selectively target such mechanisms. The final achievement is the definition of biomarkers for identifying patients who more likely should benefit for a given therapy both in terms of efficacy and reduction of the adverse reactions. Among many, two mechanisms have been defined and addressed:Both alterations lead to hypertension, organ hypertrophy, negative vascular remodeling and increased cardiovascular risk by affecting the renal Na(+) handling, through the up-regulation of the Na(+)-K(+) pump and the activation of the Src-dependent signal transduction pathway. A novel antihypertensive agent, rostafuroxin (PST2238), has been selected and developed for its ability to correct the renal Na(+)-K(+) pump abnormalities sustained by the mutant adducin and EO-dependent mechanisms. It is endowed with high potency and efficacy in reducing blood pressure (BP) and preventing organ hypertrophy in animal models representative of both adducin and EO mechanisms. At molecular level, in the kidney, rostafuroxin normalizes the enhanced activity of the Na(+)-K(+) pump induced by mutant adducin and antagonizes the EO triggering of the Src-EGFr-dependent signaling pathway leading to renal Na(+)-K(+) pump and ERK phosphorylation and activation. In the vasculature, it normalizes the increased myogenic tone caused by ouabain. A very high safety ratio and the absence of interaction with other mechanisms involved in BP regulation, together with evidence of high tolerability and efficacy in hypertensive patients indicate rostafuroxin as the first example of a new class of antihypertensive agents designed to antagonize adducin and

  5. Magnesium Counteracts Vascular Calcification: Passive Interference or Active Modulation?

    Science.gov (United States)

    Ter Braake, Anique D; Shanahan, Catherine M; de Baaij, Jeroen H F

    2017-08-01

    Over the last decade, an increasing number of studies report a close relationship between serum magnesium concentration and cardiovascular disease risk in the general population. In end-stage renal disease, an association was found between serum magnesium and survival. Hypomagnesemia was identified as a strong predictor for cardiovascular disease in these patients. A substantial body of in vitro and in vivo studies has identified a protective role for magnesium in vascular calcification. However, the precise mechanisms and its contribution to cardiovascular protection remain unclear. There are currently 2 leading hypotheses: first, magnesium may bind phosphate and delay calcium phosphate crystal growth in the circulation, thereby passively interfering with calcium phosphate deposition in the vessel wall. Second, magnesium may regulate vascular smooth muscle cell transdifferentiation toward an osteogenic phenotype by active cellular modulation of factors associated with calcification. Here, the data supporting these major hypotheses are reviewed. The literature supports both a passive inorganic phosphate-buffering role reducing hydroxyapatite formation and an active cell-mediated role, directly targeting vascular smooth muscle transdifferentiation. However, current evidence relies on basic experimental designs that are often insufficient to delineate the underlying mechanisms. The field requires more advanced experimental design, including determination of intracellular magnesium concentrations and the identification of the molecular players that regulate magnesium concentrations in vascular smooth muscle cells. © 2017 American Heart Association, Inc.

  6. Benfotiamine counteracts smoking-induced vascular dysfunction in healthy smokers.

    Science.gov (United States)

    Stirban, Alin; Nandrean, Simona; Kirana, Stanley; Götting, Christian; Veresiu, Ioan Andrei; Tschoepe, Diethelm

    2012-01-01

    Background. Smoking induces endothelial dysfunction (ED) mainly by exacerbating oxidative stress (OS) and inflammation. Benfotiamine, a thiamine prodrug with high bioavailability, prevents nicotine-induced vascular dysfunction in rats. It remained unknown whether this effect also occurs in humans. Methods. Therefore, 20 healthy volunteers (mean age: 38 years) were investigated twice, 7-10 days apart in a randomized, cross-over, and investigator-blinded design. Vascular function was assessed by flow-mediated vasodilatation (FMD) of the brachial artery and by measurements of the soluble vascular cell adhesion molecule (sVCAM)-1. Investigations were performed after an overnight fast as well as 20 minutes after one cigarette smoking. On another day, the same procedure was applied following a 3-day oral therapy with benfotiamine (1050 mg/day). Ten patients were randomized to start with smoking alone, and ten started with benfotiamine. Results. Results are expressed as (mean ± SEM). Smoking acutely induced a decrease in FMD by 50% ((∗∗)P benfotiamine treatment to 25%(∗§) ((∗)P benfotiamine. The endothelium-independent vasodilatation remained unaltered between days. Conclusion. In healthy volunteers, smoking blunts vascular function mirrored by a decrease in FMD and an increase in sVCAM-1. Short-term treatment with benfotiamine significantly reduces these effects, showing protective vascular properties.

  7. PHB Biosynthesis Counteracts Redox Stress in Herbaspirillum seropedicae

    Directory of Open Access Journals (Sweden)

    Marcelo B. Batista

    2018-03-01

    Full Text Available The ability of bacteria to produce polyhydroxyalkanoates such as poly(3-hydroxybutyrate (PHB enables provision of a carbon storage molecule that can be mobilized under demanding physiological conditions. However, the precise function of PHB in cellular metabolism has not been clearly defined. In order to determine the impact of PHB production on global physiology, we have characterized the properties of a ΔphaC1 mutant strain of the diazotrophic bacterium Herbaspirillum seropedicae. The absence of PHB in the mutant strain not only perturbs redox balance and increases oxidative stress, but also influences the activity of the redox-sensing Fnr transcription regulators, resulting in significant changes in expression of the cytochrome c-branch of the electron transport chain. The synthesis of PHB is itself dependent on the Fnr1 and Fnr3 proteins resulting in a cyclic dependency that couples synthesis of PHB with redox regulation. Transcriptional profiling of the ΔphaC1 mutant reveals that the loss of PHB synthesis affects the expression of many genes, including approximately 30% of the Fnr regulon.

  8. PHB Biosynthesis Counteracts Redox Stress in Herbaspirillum seropedicae.

    Science.gov (United States)

    Batista, Marcelo B; Teixeira, Cícero S; Sfeir, Michelle Z T; Alves, Luis P S; Valdameri, Glaucio; Pedrosa, Fabio de Oliveira; Sassaki, Guilherme L; Steffens, Maria B R; de Souza, Emanuel M; Dixon, Ray; Müller-Santos, Marcelo

    2018-01-01

    The ability of bacteria to produce polyhydroxyalkanoates such as poly(3-hydroxybutyrate) (PHB) enables provision of a carbon storage molecule that can be mobilized under demanding physiological conditions. However, the precise function of PHB in cellular metabolism has not been clearly defined. In order to determine the impact of PHB production on global physiology, we have characterized the properties of a Δ phaC1 mutant strain of the diazotrophic bacterium Herbaspirillum seropedicae . The absence of PHB in the mutant strain not only perturbs redox balance and increases oxidative stress, but also influences the activity of the redox-sensing Fnr transcription regulators, resulting in significant changes in expression of the cytochrome c -branch of the electron transport chain. The synthesis of PHB is itself dependent on the Fnr1 and Fnr3 proteins resulting in a cyclic dependency that couples synthesis of PHB with redox regulation. Transcriptional profiling of the Δ phaC1 mutant reveals that the loss of PHB synthesis affects the expression of many genes, including approximately 30% of the Fnr regulon.

  9. Benfotiamine Counteracts Smoking-Induced Vascular Dysfunction in Healthy Smokers

    Directory of Open Access Journals (Sweden)

    Alin Stirban

    2012-01-01

    Full Text Available Background. Smoking induces endothelial dysfunction (ED mainly by exacerbating oxidative stress (OS and inflammation. Benfotiamine, a thiamine prodrug with high bioavailability, prevents nicotine-induced vascular dysfunction in rats. It remained unknown whether this effect also occurs in humans. Methods. Therefore, 20 healthy volunteers (mean age: 38 years were investigated twice, 7–10 days apart in a randomized, cross-over, and investigator-blinded design. Vascular function was assessed by flow-mediated vasodilatation (FMD of the brachial artery and by measurements of the soluble vascular cell adhesion molecule (sVCAM-1. Investigations were performed after an overnight fast as well as 20 minutes after one cigarette smoking. On another day, the same procedure was applied following a 3-day oral therapy with benfotiamine (1050 mg/day. Ten patients were randomized to start with smoking alone, and ten started with benfotiamine. Results. Results are expressed as (mean ± SEM. Smoking acutely induced a decrease in FMD by 50% (∗∗P<0.001 versus baseline an effect significantly reduced by benfotiamine treatment to 25%∗§ (∗P<0.05 versus baseline, §P<0.05 versus smoking alone. Smoking-induced elevation in sVCAM-1 was also prevented by benfotiamine. The endothelium-independent vasodilatation remained unaltered between days. Conclusion. In healthy volunteers, smoking blunts vascular function mirrored by a decrease in FMD and an increase in sVCAM-1. Short-term treatment with benfotiamine significantly reduces these effects, showing protective vascular properties.

  10. Sexual stigma and symbolic violence experienced, enacted, and counteracted in young Africans' writing about same-sex attraction.

    Science.gov (United States)

    Winskell, Kate; Sabben, Gaëlle

    2016-07-01

    There is growing recognition of the health disparities faced by sexual minority populations and the critical role played by sexual stigma in increasing their vulnerability. Experienced, anticipated, and internalized, stigma based on sexual orientation reduces access to HIV/STI prevention and treatment services among African men who have sex with men and has been linked to compromised mental health, risk-taking, and HIV status. It is likely that similar processes undermine the health of sexual minority African women and transgender and non-binary people. There is a need for increased understanding of both the contextual factors and the cultural meanings, or symbolic violence, that inform sexual stigma and harmful stigma management strategies in contexts that are culturally and socio-politically oppressive for sexual and gender minorities. Using thematic data analysis and narrative-based methodologies, we analyzed narratives and essays on same-sex attraction contributed by young people aged 13-24 from ten African countries to a Spring 2013 scriptwriting competition on HIV, sexuality, and related themes. Submitted by 27 male and 29 female authors, the texts were written in response to a prompt inviting participants to "Tell a story about someone who is attracted to people of the same sex". We analyzed the ways in which sexual stigma and its effects are described, enacted, and counteracted in the texts. The data provide insights into the social and symbolic processes that create and sustain sexual stigma in the context of broader transnational discourses. The data shed light on psychosocial challenges faced by sexual minority youth and identify both rhetoric, stereotypes, and discourse that devalue them and representations that counteract this symbolic violence. We share our findings in the hope they may inform education and communication programming as part of multi-level efforts to improve the health and human rights of sexual minority populations in sub

  11. Melatonin counteracts changes in hypothalamic gene expression of signals regulating feeding behavior in high-fat fed rats.

    Science.gov (United States)

    Ríos-Lugo, María J; Jiménez-Ortega, Vanesa; Cano-Barquilla, Pilar; Mateos, Pilar Fernández; Spinedi, Eduardo J; Cardinali, Daniel P; Esquifino, Ana I

    2015-03-01

    Previous studies indicate that the administration of melatonin caused body weight and abdominal visceral fat reductions in rodent models of hyperadiposity. The objective of the present study performed in high-fat fed rats was to evaluate the activity of melatonin on gene expression of some medial basal hypothalamus (MBH) signals involved in feeding behavior regulation, including neuropeptide Y (NPY), proopiomelanocortin (POMC), prolactin-releasing peptide (PrRP), leptin- and insulin-receptors (R) and insulin-R substrate (IRS)-1 and -2. Blood levels of leptin and adiponectin were also measured. Adult Wistar male rats were divided into four groups (n=16 per group): (i) control diet (3% fat); (ii) high-fat (35%) diet; (iii) high-fat diet+melatonin; (iv) control diet+melatonin. Rats had free access to high-fat or control chow and one of the following drinking solutions: (a) tap water; (b) 25 μg/mL of melatonin. After 10 weeks, the high-fat fed rats showed augmented MBH mRNA levels of NPY, leptin-R, PrRP, insulin-R, IRS-1 and IRS-2. The concomitant administration of melatonin counteracted this increase. Feeding of rats with a high-fat diet augmented expression of the MBH POMC gene through an effect insensitive to melatonin treatment. The augmented levels of circulating leptin and adiponectin seen in high-fat fed rats were counteracted by melatonin as was the augmented body weight: melatonin significantly attenuated a body weight increase in high-fat fed rats without affecting chow or water consumption. Melatonin augmented plasma leptin and adiponectin in control rats. The results indicate that an effect on gene expression of feeding behavior signals at the central nervous system (CNS) may complement a peripheral rise of the energy expenditure produced by melatonin to decrease body weight in high-fat fed rats.

  12. Interspecific competition counteracts negative effects of dispersal on adaptation of an arthropod herbivore to a new host.

    Science.gov (United States)

    Alzate, A; Bisschop, K; Etienne, R S; Bonte, D

    2017-11-01

    Dispersal and competition have both been suggested to drive variation in adaptability to a new environment, either positively or negatively. A simultaneous experimental test of both mechanisms is however lacking. Here, we experimentally investigate how population dynamics and local adaptation to a new host plant in a model species, the two-spotted spider mite (Tetranychus urticae), are affected by dispersal from a stock population (no-adapted) and competition with an already adapted spider mite species (Tetranychus evansi). For the population dynamics, we find that competition generally reduces population size and increases the risk of population extinction. However, these negative effects are counteracted by dispersal. For local adaptation, the roles of competition and dispersal are reversed. Without competition, dispersal exerts a negative effect on adaptation (measured as fecundity) to a novel host and females receiving the highest number of immigrants performed similarly to the stock population females. By contrast, with competition, adding more immigrants did not result in a lower fecundity. Females from populations with competition receiving the highest number of immigrants had a significantly higher fecundity than females from populations without competition (same dispersal treatment) and than the stock population females. We suggest that by exerting a stronger selection on the adapting populations, competition can counteract the migration load effect of dispersal. Interestingly, adaptation to the new host does not significantly reduce performance on the ancestral host, regardless of dispersal rate or competition. Our results highlight that assessments of how species can adapt to changing conditions need to jointly consider connectivity and the community context. © 2017 The Authors. Journal of Evolutionary Biology Published by John Wiley & Sons ltd on Behalf of European Society for Evolutionary Biology.

  13. Nature gives us strength: exposure to nature counteracts ego-depletion.

    Science.gov (United States)

    Chow, Jason T; Lau, Shun

    2015-01-01

    Previous research rarely investigated the role of physical environment in counteracting ego-depletion. In the present research, we hypothesized that exposure to natural environment counteracts ego-depletion. Three experiments were conducted to test this hypothesis. In Experiment 1, initially depleted participants who viewed pictures of nature scenes showed greater persistence on a subsequent anagram task than those who were given a rest period. Experiment 2 expanded upon this finding by showing that natural environment enhanced logical reasoning performance after ego-depleting task. Experiment 3 adopted a two- (depletion vs. no-depletion) -by-two (nature exposure vs. urban exposure) factorial design. We found that nature exposure moderated the effect of depletion on anagram task performance. Taken together, the present studies offer a viable and novel strategy to mitigate the negative impacts of ego-depletion.

  14. Alpha-Tocopherol Counteracts the Cytotoxicity Induced by Ochratoxin A in Primary Porcine Fibroblasts

    DEFF Research Database (Denmark)

    Fusi, Elenora; Rebucci, Raffaella; Pecorini, Chiara

    2010-01-01

    The aims of the current study were to determine the half-lethal concentration of ochratoxin A (OTA) as well as the levels of lactate dehydrogenase release and DNA fragmentation induced by OTA in primary porcine fibroblasts, and to examine the role of α-tocopherol in counteracting its toxicity....... Cells showed a dose-, time- and origin-dependent (ear vs. embryo) sensitivity to ochratoxin A. Pre-incubation for 3 h with 1 nM α-tocopherol significantly (P tocopherol...

  15. Neurosteroid 3α-androstanediol efficiently counteracts paclitaxel-induced peripheral neuropathy and painful symptoms.

    Directory of Open Access Journals (Sweden)

    Laurence Meyer

    Full Text Available Painful peripheral neuropathy belongs to major side-effects limiting cancer chemotherapy. Paclitaxel, widely used to treat several cancers, induces neurological symptoms including burning pain, allodynia, hyperalgesia and numbness. Therefore, identification of drugs that may effectively counteract paclitaxel-induced neuropathic symptoms is crucial. Here, we combined histopathological, neurochemical, behavioral and electrophysiological methods to investigate the natural neurosteroid 3α-androstanediol (3α-DIOL ability to counteract paclitaxel-evoked peripheral nerve tissue damages and neurological symptoms. Prophylactic or corrective 3α-DIOL treatment (4 mg/kg/2 days prevented or suppressed PAC-evoked heat-thermal hyperalgesia, cold-allodynia and mechanical allodynia/hyperalgesia, by reversing to normal, decreased thermal and mechanical pain thresholds of PAC-treated rats. Electrophysiological studies demonstrated that 3α-DIOL restored control values of nerve conduction velocity and action potential peak amplitude significantly altered by PAC-treatment. 3α-DIOL also repaired PAC-induced nerve damages by restoring normal neurofilament-200 level in peripheral axons and control amount of 2',3'-cyclic-nucleotide-3'-phosphodiesterase in myelin sheaths. Decreased density of intraepidermal nerve fibers evoked by PAC-therapy was also counteracted by 3α-DIOL treatment. More importantly, 3α-DIOL beneficial effects were not sedation-dependent but resulted from its neuroprotective ability, nerve tissue repairing capacity and long-term analgesic action. Altogether, our results showing that 3α-DIOL efficiently counteracted PAC-evoked painful symptoms, also offer interesting possibilities to develop neurosteroid-based strategies against chemotherapy-induced peripheral neuropathy. This article shows that the prophylactic or corrective treatment with 3α-androstanediol prevents or suppresses PAC-evoked painful symptoms and peripheral nerve dysfunctions in

  16. Counteracting Animal Homelessness and Providing Care for Stray Animals as a Task of a Commune

    OpenAIRE

    Szalewska, Małgorzata

    2017-01-01

    The analysis of Polish binding law acts allows one to assume that, on normative level, the obligation of public administration to provide care for stray animals is deeply embedded. Both the Animal Protection Act, as well as the Act on Maintaining Cleanliness, indicate the tasks of a commune in the scope of providing care for stray animals, catching homeless animals and counteracting their homelessness. Simultaneously, the analysis of jurisdiction, and inquiries as well as considerations emerg...

  17. Strategies used to counteract bullying in schools : a comparative study / Wendy Batterbee

    OpenAIRE

    Batterbee, Wendy Ann

    2007-01-01

    This is an in-depth comparative study of the strategies used to counteract bullying at schools. It provides an international perspective on such strategies: Studies in South African schools are used to provide an African perspective: Australian research is used to provide an Oceanian perspective: Japanese research to provide an Asian perspective; and research conducted in England is used to provide an European perspective on bullying at schools. The extent and nature of bullying in schools...

  18. Physical activity counteracts tumor cell growth in colon carcinoma C26-injected muscles: an interim report

    Directory of Open Access Journals (Sweden)

    Charlotte Hiroux

    2016-06-01

    Full Text Available Skeletal muscle tissue is a rare site of tumor metastasis but is the main target of the degenerative processes occurring in cancer-associated cachexia syndrome. Beneficial effects of physical activity in counteracting cancer-related muscle wasting have been described in the last decades. Recently it has been shown that, in tumor xeno-transplanted mouse models, physical activity is able to directly affect tumor growth by modulating inflammatory responses in the tumor mass microenvironment. Here, we investigated the effect of physical activity on tumor cell growth in colon carcinoma C26 cells injected tibialis anterior muscles of BALB/c mice. Histological analyses revealed that 4 days of voluntary wheel running significantly counteracts tumor cell growth in C26-injected muscles compared to the non-injected sedentary controls. Since striated skeletal muscle tissue is the site of voluntary contraction, our results confirm that physical activity can also directly counteract tumor cell growth in a metabolically active tissue that is usually not a target for metastasis.

  19. Gradient pre-emphasis to counteract first-order concomitant fields on asymmetric MRI gradient systems.

    Science.gov (United States)

    Tao, Shengzhen; Weavers, Paul T; Trzasko, Joshua D; Shu, Yunhong; Huston, John; Lee, Seung-Kyun; Frigo, Louis M; Bernstein, Matt A

    2017-06-01

    To develop a gradient pre-emphasis scheme that prospectively counteracts the effects of the first-order concomitant fields for any arbitrary gradient waveform played on asymmetric gradient systems, and to demonstrate the effectiveness of this approach using a real-time implementation on a compact gradient system. After reviewing the first-order concomitant fields that are present on asymmetric gradients, we developed a generalized gradient pre-emphasis model assuming arbitrary gradient waveforms to counteract their effects. A numerically straightforward, easily implemented approximate solution to this pre-emphasis problem was derived that was compatible with the current hardware infrastructure of conventional MRI scanners for eddy current compensation. The proposed method was implemented on the gradient driver subsystem, and its real-time use was tested using a series of phantom and in vivo data acquired from two-dimensional Cartesian phase-difference, echo-planar imaging, and spiral acquisitions. The phantom and in vivo results demonstrated that unless accounted for, first-order concomitant fields introduce considerable phase estimation error into the measured data and result in images with spatially dependent blurring/distortion. The resulting artifacts were effectively prevented using the proposed gradient pre-emphasis. We have developed an efficient and effective gradient pre-emphasis framework to counteract the effects of first-order concomitant fields of asymmetric gradient systems. Magn Reson Med 77:2250-2262, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  20. Neural signal for counteracting pre-action bias in the centromedian thalamic nucleus

    Directory of Open Access Journals (Sweden)

    Takafumi eMinamimoto

    2014-01-01

    Full Text Available Most of our daily actions are selected and executed involuntarily under familiar situations by the guidance of internal drives, such as motivation. The behavioral tendency or biasing towards one over others reflects the action-selection process in advance of action execution (i.e., pre-action bias. Facing unexpected situations, however, pre-action bias should be withdrawn and replaced by an alternative that is suitable for the situation (i.e., counteracting bias. To understand the neural mechanism for the counteracting process, we studied the neural activity of the thalamic centromedian (CM nucleus in monkeys performing GO-NOGO task with asymmetrical or symmetrical reward conditions. The monkeys reacted to GO signal faster in large-reward condition, indicating behavioral bias toward large reward. In contrast, they responded slowly in small-reward condition, suggesting a conflict between internal drive and external demand. We found that neurons in the CM nucleus exhibited phasic burst discharges after GO and NOGO instructions especially when they were associated with small reward. The small-reward preference was positively correlated with the strength of behavioral bias toward large reward. The small-reward preference disappeared when only NOGO action was requested. The timing of activation predicted the timing of action opposed to bias. These results suggest that CM signals the discrepancy between internal pre-action bias and external demand, and mediates the counteracting process — resetting behavioral bias and leading to execution of opposing action.

  1. Comparative analysis of successful practices of corruption counteraction in the sphere of school education in foreign countries

    Directory of Open Access Journals (Sweden)

    Valentina Vladimirovna Tereshkova

    2015-03-01

    Full Text Available Objective to analyze the practice of corruption counteraction in the sphere of school education in foreign countries. Methods comparativelegal method polling content analysis of documents expert evaluation testing of experts with an international technique Questionnaire Profile of Demand. Results the need for the corruption counteraction program is stated in Art. 13.3 of the Federal Law ldquoOn corruption counteractionrdquoand Methodological recommendations of the Russian Ministry of Labor on corruption risks evaluation when implementing functions but no definite measures for corruption counteraction in educational organizations have been formulated. Nevertheless the controlling bodies inquire for information on such measures. As an example wecitean inquiry of Krasnoyarsk Oktyabrskiy region Prosecutorrsquos Office to educational organizations of October 21 2014 no. 86012014 ldquoOn measures for corruption counteraction in the sphere of educationrdquo. Scientific novelty summarizing the experience of corruption counteraction in the sphere of education in foreign countries and the expertsrsquo opinion of the specialist of international organizations allowed to formulate a number of recommendations for the Russian educational establishments. Practical value the experience of corruption counteraction in foreign countries will allow the head of an educational establishment to choose those of the proposed measures which will be efficient in corruption prevention and to elaborate an efficient program for corruption prevention. nbsp

  2. Regulating Rumination by Anger: Evidence for the Mutual Promotion and Counteraction (MPMC Theory of Emotionality

    Directory of Open Access Journals (Sweden)

    Jun Zhan

    2017-12-01

    Full Text Available Unlike the strategy of cognitive regulation that relies heavily on the top-down control function of the prefrontal cortex (PFC, which was recently found may be critically impaired in stressful situations, traditional Chinese philosophy and medicine views different types of emotionality as having mutual promotion and counteraction (MPMC relationships, implying a novel approach that requires less cognition to emotional regulation. Actually, our previous studies have indicated that anger responses could be successfully regulated via the induction of sadness, and this efficiency could not be influenced by stress, thus providing evidences for the hypothesis of “sadness counteracts anger” (SCA proposed by the MPMC theory of emotionality (Zhan et al., 2015, 2017. In this study, we experimentally examined the MPMC hypothesis that “anger counteracts rumination” (ACR which postulates that rumination may be alleviated by the anger emotion. In Study 1, all participants were initially caused state rumination and then induced anger, joy or neutral mood, the results showed that the rumination-related affect was alleviated after anger induction relative to that after joy or neutral mood induction. In Study 2, female participants with high trait rumination were recruited and divided into two groups for exposure to an anger or neutral emotion intervention, the result indicated that the anger intervention group exhibited a greater decline in trait rumination than the neutral emotion intervention group. These findings provided preliminary evidence supporting the hypothesis of ACR, which suggested a new strategy that employs less cognitive resources to regulating state and trait rumination by inducing anger.

  3. Regulating Rumination by Anger: Evidence for the Mutual Promotion and Counteraction (MPMC) Theory of Emotionality

    Science.gov (United States)

    Zhan, Jun; Tang, Fan; He, Mei; Fan, Jin; Xiao, Jing; Liu, Chang; Luo, Jing

    2017-01-01

    Unlike the strategy of cognitive regulation that relies heavily on the top-down control function of the prefrontal cortex (PFC), which was recently found may be critically impaired in stressful situations, traditional Chinese philosophy and medicine views different types of emotionality as having mutual promotion and counteraction (MPMC) relationships, implying a novel approach that requires less cognition to emotional regulation. Actually, our previous studies have indicated that anger responses could be successfully regulated via the induction of sadness, and this efficiency could not be influenced by stress, thus providing evidences for the hypothesis of “sadness counteracts anger” (SCA) proposed by the MPMC theory of emotionality (Zhan et al., 2015, 2017). In this study, we experimentally examined the MPMC hypothesis that “anger counteracts rumination” (ACR) which postulates that rumination may be alleviated by the anger emotion. In Study 1, all participants were initially caused state rumination and then induced anger, joy or neutral mood, the results showed that the rumination-related affect was alleviated after anger induction relative to that after joy or neutral mood induction. In Study 2, female participants with high trait rumination were recruited and divided into two groups for exposure to an anger or neutral emotion intervention, the result indicated that the anger intervention group exhibited a greater decline in trait rumination than the neutral emotion intervention group. These findings provided preliminary evidence supporting the hypothesis of ACR, which suggested a new strategy that employs less cognitive resources to regulating state and trait rumination by inducing anger. PMID:29249998

  4. Violence and Means to Counteract Power: a View to Migrant Indigenous Women in Mexico

    Directory of Open Access Journals (Sweden)

    Sara María Lara Flores

    2003-01-01

    Full Text Available The article analizes the conditions in which women farmers incorporate into México’s exports processes. This sector has a great need of labour at the national level, which in turn brings about many migration fluxes in which indigenous women play an important role. The study shows how this feminine incorporation into the labour market triggers gender as well as ethnic inequalities that manifest themselves in a segmentation within the branches and sectors of the national economy. Also, the article describes the means to which indigenous women turn to in order to counteract the actual and symbolic violence they are submitted to.

  5. Postconditioning with inhaled carbon monoxide counteracts apoptosis and neuroinflammation in the ischemic rat retina.

    Directory of Open Access Journals (Sweden)

    Nils Schallner

    Full Text Available Ischemia and reperfusion injury (I/R of neuronal structures and organs is associated with increased morbidity and mortality due to neuronal cell death. We hypothesized that inhalation of carbon monoxide (CO after I/R injury ('postconditioning' would protect retinal ganglion cells (RGC.Retinal I/R injury was performed in Sprague-Dawley rats (n = 8 by increasing ocular pressure (120 mmHg, 1 h. Rats inhaled room air or CO (250 ppm for 1 h immediately following ischemia or with 1.5 and 3 h latency. Retinal tissue was harvested to analyze Bcl-2, Bax, Caspase-3, HO-1 expression and phosphorylation of the nuclear transcription factor (NF-κB, p38 and ERK-1/2 MAPK. NF-κB activation was determined and inhibition of ERK-1/2 was performed using PD98059 (2 mg/kg. Densities of fluorogold prelabeled RGC were analyzed 7 days after injury. Microglia, macrophage and Müller cell activation and proliferation were evaluated by Iba-1, GFAP and Ki-67 staining.Inhalation of CO after I/R inhibited Bax and Caspase-3 expression (Bax: 1.9 ± 0.3 vs. 1.4 ± 0.2, p = 0.028; caspase-3: 2.0 ± 0.2 vs. 1.5 ± 0.1, p = 0.007; mean ± S.D., fold induction at 12 h, while expression of Bcl-2 was induced (1.2 ± 0.2 vs. 1.6 ± 0.2, p = 0.001; mean ± S.D., fold induction at 12 h. CO postconditioning suppressed retinal p38 phosphorylation (p = 0.023 at 24 h and induced the phosphorylation of ERK-1/2 (p<0.001 at 24 h. CO postconditioning inhibited the expression of HO-1. The activation of NF-κB, microglia and Müller cells was potently inhibited by CO as well as immigration of proliferative microglia and macrophages into the retina. CO protected I/R-injured RGC with a therapeutic window at least up to 3 h (n = 8; RGC/mm(2; mean ± S.D.: 1255 ± 327 I/R only vs. 1956 ± 157 immediate CO treatment, vs. 1830 ± 109 1.5 h time lag and vs. 1626 ± 122 3 h time lag; p<0.001. Inhibition of ERK-1/2 did not counteract the CO effects (RGC/mm(2: 1956 ± 157 vs. 1931 ± 124, mean ± S.D., p

  6. CNF1 Enhances Brain Energy Content and Counteracts Spontaneous Epileptiform Phenomena in Aged DBA/2J Mice.

    Directory of Open Access Journals (Sweden)

    Sara Travaglione

    Full Text Available Epilepsy, one of the most common conditions affecting the brain, is characterized by neuroplasticity and brain cell energy defects. In this work, we demonstrate the ability of the Escherichia coli protein toxin cytotoxic necrotizing factor 1 (CNF1 to counteract epileptiform phenomena in inbred DBA/2J mice, an animal model displaying genetic background with an high susceptibility to induced- and spontaneous seizures. Via modulation of the Rho GTPases, CNF1 regulates actin dynamics with a consequent increase in spine density and length in pyramidal neurons of rat visual cortex, and influences the mitochondrial homeostasis with remarkable changes in the mitochondrial network architecture. In addition, CNF1 improves cognitive performances and increases ATP brain content in mouse models of Rett syndrome and Alzheimer's disease. The results herein reported show that a single dose of CNF1 induces a remarkable amelioration of the seizure phenotype, with a significant augmentation in neuroplasticity markers and in cortex mitochondrial ATP content. This latter effect is accompanied by a decrease in the expression of mitochondrial fission proteins, suggesting a role of mitochondrial dynamics in the CNF1-induced beneficial effects on this epileptiform phenotype. Our results strongly support the crucial role of brain energy homeostasis in the pathogenesis of certain neurological diseases, and suggest that CNF1 could represent a putative new therapeutic tool for epilepsy.

  7. Human Neural Stem Cell Aging Is Counteracted by α-Glycerylphosphorylethanolamine.

    Science.gov (United States)

    Daniele, Simona; Da Pozzo, Eleonora; Iofrida, Caterina; Martini, Claudia

    2016-07-20

    Neural stem cells (NSCs) represent a subpopulation of cells, located in specific regions of the adult mammalian brain, with the ability of self-renewing and generating neurons and glia. In aged NSCs, modifications in the amount and composition of membrane proteins/lipids, which lead to a reduction in membrane fluidity and cholinergic activities, have been reported. In this respect, molecules that are effective at normalizing the membrane composition and cholinergic signaling could counteract stem cell aging. α-Glycerylphosphorylethanolamine (GPE), a nootropic drug, plays a role in phospholipid biosynthesis and acetylcholine release. Herein, GPE was assayed on human NSC cultures and on hydroxyurea-aged cells. Using cell counting, colorimetric, and fluorimetric analyses, immunoenzymatic assays, and real time PCR experiments, NSC culture proliferation, senescence, reactive oxygen species, and ADP/ATP levels were assessed. Aged NSCs exhibited cellular senescence, decreased proliferation, and an impairment in mitochondrial metabolism. These changes included a substantial induction in the nuclear factor NF-κB, a key inflammatory mediator. GPE cell treatment significantly protected the redox state and functional integrity of mitochondria, and counteracted senescence and NF-κB activation. In conclusion, our data show the beneficial properties of GPE in this model of stem cell aging.

  8. Retrograde Signaling from Progranulin to Sort1 Counteracts Synapse Elimination in the Developing Cerebellum.

    Science.gov (United States)

    Uesaka, Naofumi; Abe, Manabu; Konno, Kohtarou; Yamazaki, Maya; Sakoori, Kazuto; Watanabe, Takaki; Kao, Tzu-Huei; Mikuni, Takayasu; Watanabe, Masahiko; Sakimura, Kenji; Kano, Masanobu

    2018-02-21

    Elimination of redundant synapses formed early in development and strengthening of necessary connections are crucial for shaping functional neural circuits. Purkinje cells (PCs) in the neonatal cerebellum are innervated by multiple climbing fibers (CFs) with similar strengths. A single CF is strengthened whereas the other CFs are eliminated in each PC during postnatal development. The underlying mechanisms, particularly for the strengthening of single CFs, are poorly understood. Here we report that progranulin, a multi-functional growth factor implicated in the pathogenesis of frontotemporal dementia, strengthens developing CF synaptic inputs and counteracts their elimination from postnatal day 11 to 16. Progranulin derived from PCs acts retrogradely onto its putative receptor Sort1 on CFs. This effect is independent of semaphorin 3A, another retrograde signaling molecule that counteracts CF synapse elimination. We propose that progranulin-Sort1 signaling strengthens and maintains developing CF inputs, and may contribute to selection of single "winner" CFs that survive synapse elimination. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Gemcitabine-induced CXCL8 expression counteracts its actions by inducing tumor neovascularization

    International Nuclear Information System (INIS)

    Song, Yao; Baba, Tomohisa; Li, Ying-Yi; Furukawa, Kaoru; Tanabe, Yamato; Matsugo, Seiichi; Sasaki, Soichiro; Mukaida, Naofumi

    2015-01-01

    Patients with pancreatic ductal adenocarcinoma (PDAC) are frequently complicated with metastatic disease or locally advanced tumors, and consequently need chemotherapy. Gemcitabine is commonly used for PDAC treatment, but with limited efficacy. The capacity of gemcitabine to generate reactive oxygen species (ROS) in human pancreatic cancer cells, prompted us to examine its effects on the expression of pro-inflammatory cytokines and chemokines. We observed that gemcitabine enhanced selectively the expression of CXCL8 in human pancreatic cancer cells through ROS generation and NF-κB activation. In vitro blocking of CXCL8 failed to modulate gemcitabine-mediated inhibition of cell proliferation in human pancreatic cancer cells. Gemcitabine also enhanced CXCL8 expression in pancreatic cancer cells in xenografted tumor tissues. Moreover, anti-CXCL8 antibody treatment in vivo attenuated tumor formation as well as intra-tumoral vascularity in nude mice, which were transplanted with Miapaca-2 cells and treated with gemcitabine. Thus, gemcitabine-induced CXCL8 may counteract the drug through inducing neovascularization. - Highlights: • Gemcitabine induced CXCL8 expression in human pancreatic cancer cells. • CXCL8 expression required ROS generation and NF-κB activation. • CXCL8 did not affect in vitro proliferation of human pancreatic cancer cells. • CXCL8 in vivo counteracted gemcitabine by inducing neovascularization

  10. Acidosis counteracts itch tachyphylaxis to consecutive pruritogen exposure dependent on acid-sensing ion channel 3.

    Science.gov (United States)

    Jiang, Yi-Ming; Huang, Chen; Peng, Zhong; Han, Shao-Ling; Li, Wei-Guang; Zhu, Michael Xi; Xu, Tian-Le

    2017-01-01

    Tachyphylaxis of itch refers to a markedly reduced scratching response to consecutive exposures of a pruritogen, a process thought to protect against tissue damage by incessant scratching and to become disrupted in chronic itch. Here, we report that a strong stimulation of the Mas-related G-protein-coupled receptor C11 by its agonist, Ser-Leu-Ile-Gly-Arg-Leu-NH 2 (SL-NH 2 ) or bovine adrenal medulla 8-22 peptide, via subcutaneous injection in mice induces tachyphylaxis to the subsequent application of SL-NH 2 to the same site. Notably, co-application of acid and SL-NH 2 following the initial injection of the pruritogen alone counteracted itch tachyphylaxis by augmenting the scratching behaviors in wild-type but not in acid-sensing ion channel 3-null, animals. Using an activity-dependent silencing strategy, we identified that acid-sensing ion channel 3-mediated itch enhancement mainly occurred via the Mas-related G-protein-coupled receptor C11-responsive sensory neurons. Together, our results indicate that acid-sensing ion channel 3, activated by concomitant acid and certain pruritogens, constitute a novel signaling pathway that counteracts itch tachyphylaxis to successive pruritogenic stimulation, which likely contributes to chronic itch associated with tissue acidosis.

  11. Gemcitabine-induced CXCL8 expression counteracts its actions by inducing tumor neovascularization

    Energy Technology Data Exchange (ETDEWEB)

    Song, Yao; Baba, Tomohisa [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan); Li, Ying-Yi [Cancer Research Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China); Furukawa, Kaoru; Tanabe, Yamato [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan); School of Natural System Bioengineering Course, College of Science and Engineering, Kanazawa University, Kanazawa, Ishikawa (Japan); Matsugo, Seiichi [School of Natural System Bioengineering Course, College of Science and Engineering, Kanazawa University, Kanazawa, Ishikawa (Japan); Sasaki, Soichiro [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan); Mukaida, Naofumi, E-mail: mukaida@staff.kanazawa-u.ac.jp [Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan)

    2015-03-06

    Patients with pancreatic ductal adenocarcinoma (PDAC) are frequently complicated with metastatic disease or locally advanced tumors, and consequently need chemotherapy. Gemcitabine is commonly used for PDAC treatment, but with limited efficacy. The capacity of gemcitabine to generate reactive oxygen species (ROS) in human pancreatic cancer cells, prompted us to examine its effects on the expression of pro-inflammatory cytokines and chemokines. We observed that gemcitabine enhanced selectively the expression of CXCL8 in human pancreatic cancer cells through ROS generation and NF-κB activation. In vitro blocking of CXCL8 failed to modulate gemcitabine-mediated inhibition of cell proliferation in human pancreatic cancer cells. Gemcitabine also enhanced CXCL8 expression in pancreatic cancer cells in xenografted tumor tissues. Moreover, anti-CXCL8 antibody treatment in vivo attenuated tumor formation as well as intra-tumoral vascularity in nude mice, which were transplanted with Miapaca-2 cells and treated with gemcitabine. Thus, gemcitabine-induced CXCL8 may counteract the drug through inducing neovascularization. - Highlights: • Gemcitabine induced CXCL8 expression in human pancreatic cancer cells. • CXCL8 expression required ROS generation and NF-κB activation. • CXCL8 did not affect in vitro proliferation of human pancreatic cancer cells. • CXCL8 in vivo counteracted gemcitabine by inducing neovascularization.

  12. Lactobacillus salivarius REN counteracted unfavorable 4-nitroquinoline-1-oxide-induced changes in colonic microflora of rats.

    Science.gov (United States)

    Zhang, Ming; Qiao, Xuewei; Zhao, Liang; Jiang, Lu; Ren, Fazheng

    2011-12-01

    Probiotics and carcinogens both have a significant effect on the microfloral composition of the human intestine. The objective of this study was to investigate the impact of an important carcinogen, 4-Nitroquinoline-1-Oxide on colonic microflora and the efficacy of the probiotic Lactobacillus salivarius REN as an agent of counteracting these effects. Using denaturing gradient gel electrophoresis (DGGE) combined with redundancy analysis, we demonstrated that both 4-Nitroquinoline-1-Oxide and L. salivarius REN significantly altered the bacterial communities of rat colons. A total of 27 bacterial strains were identified as being affected by treatment with 4-Nitroquinoline-1-Oxide or L. salivarius REN using a t-value biplot combined with band sequencing. 4-Nitroquinoline-1-Oxide treatment increased the abundance of two potential pathogens (one Helicobacter strain and one Desulfovibrio strain), as well as reducing the abundance of two potentially beneficial strains (one Ruminococcaceae strain and one Rumen bacteria). The Helicobacter strain was initally detected in carcinogen-treated rat intestinal microflora, but L. salivarius REN treatment effectively suppressed the growth of the Helicobacter strain. These results suggested that L. salivarius REN may be a potential probiotic, efficiently acting against the initial infection with, and the growth of pathogenic bacteria.

  13. Putrescine biosynthesis in Lactococcus lactis is transcriptionally activated at acidic pH and counteracts acidification of the cytosol.

    Science.gov (United States)

    Del Rio, Beatriz; Linares, Daniel; Ladero, Victor; Redruello, Begoña; Fernandez, Maria; Martin, Maria Cruz; Alvarez, Miguel A

    2016-11-07

    Lactococcus lactis subsp. cremoris CECT 8666 is a lactic acid bacterium that synthesizes the biogenic amine putrescine from agmatine via the agmatine deiminase (AGDI) pathway. The AGDI genes cluster includes aguR. This encodes a transmembrane protein that functions as a one-component signal transduction system, the job of which is to sense the agmatine concentration of the medium and accordingly regulate the transcription of the catabolic operon aguBDAC. The latter encodes the proteins necessary for agmatine uptake and its conversion into putrescine. This work reports the effect of extracellular pH on putrescine biosynthesis and on the genetic regulation of the AGDI pathway. Increased putrescine biosynthesis was detected at acidic pH (pH5) compared to neutral pH. Acidic pH induced the transcription of the catabolic operon via the activation of the aguBDAC promoter PaguB. However, the external pH had no significant effect on the activity of the aguR promoter PaguR, or on the transcription of the aguR gene. The transcriptional activation of the AGDI pathway was also found to require a lower agmatine concentration at pH5 than at neutral pH. Finally, the following of the AGDI pathway counteracted the acidification of the cytoplasm under acidic external conditions, suggesting it to provide protection against acid stress. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Chronic Exercise Reduces CETP and Mesterolone Treatment Counteracts Exercise Benefits on Plasma Lipoproteins Profile: Studies in Transgenic Mice.

    Science.gov (United States)

    Casquero, Andrea Camargo; Berti, Jairo Augusto; Teixeira, Laura Lauand Sampaio; de Oliveira, Helena Coutinho Franco

    2017-12-01

    Regular exercise and anabolic androgenic steroids have opposing effects on the plasma lipoprotein profile and risk of cardio-metabolic diseases in humans. Studies in humans and animal models show conflicting results. Here, we used a mice model genetically modified to mimic human lipoprotein profile and metabolism. They under-express the endogenous LDL receptor gene (R1) and express a human transgene encoding the cholesteryl ester transfer protein (CETP), normally absent in mice. The present study was designed to evaluate the independent and interactive effects of testosterone supplementation, exercise training and CETP expression on the plasma lipoprotein profile and CETP activity. CETP/R1 and R1 mice were submitted to a 6-week swimming training and mesterolone (MEST) supplementation in the last 3 weeks. MEST treatment increased markedly LDL levels (40%) in sedentary CETP/R1 mice and reduced HDL levels in exercised R1 mice (18%). A multifactorial ANOVA revealed the independent effects of each factor, as follows. CETP expression reduced HDL (21%) and increased non-HDL (15%) fractions. MEST treatment increased the VLDL concentrations (42%) regardless of other interventions. Exercise training reduced triacylglycerol (25%) and free fatty acids (20%), increased both LDL and HDL (25-33%), and reduced CETP (19%) plasma levels. Significant factor interactions showed that the increase in HDL induced by exercise is explained by reducing CETP activity and that MEST blunted the exercise-induced elevation of HDL-cholesterol. These results reinforce the positive metabolic effects of exercise, resolved a controversy about CETP response to exercise and evidenced MEST potency to counteract specific exercise benefits.

  15. Sucrose counteracts the anti-inflammatory effect of fish oil in adipose tissue and increases obesity development in mice

    DEFF Research Database (Denmark)

    Ma, Tao; Liaset, Bjørn; Hao, Qin

    2011-01-01

    Polyunsaturated n-3 fatty acids (n-3 PUFAs) are reported to protect against high fat diet-induced obesity and inflammation in adipose tissue. Here we aimed to investigate if the amount of sucrose in the background diet influences the ability of n-3 PUFAs to protect against diet-induced obesity, a...

  16. Metabolic adaptations may counteract ventilatory adaptations of intermittent hypoxic exposure during submaximal exercise at altitudes up to 4000 m.

    Directory of Open Access Journals (Sweden)

    Martin Faulhaber

    Full Text Available Intermittent hypoxic exposure (IHE has been shown to induce aspects of altitude acclimatization which affect ventilatory, cardiovascular and metabolic responses during exercise in normoxia and hypoxia. However, knowledge on altitude-dependent effects and possible interactions remains scarce. Therefore, we determined the effects of IHE on cardiorespiratory and metabolic responses at different simulated altitudes in the same healthy subjects. Eight healthy male volunteers participated in the study and were tested before and 1 to 2 days after IHE (7 × 1 hour at 4500 m. The participants cycled at 2 submaximal workloads (corresponding to 40% and 60% of peak oxygen uptake at low altitude at simulated altitudes of 2000 m, 3000 m, and 4000 m in a randomized order. Gas analysis was performed and arterial oxygen saturation, blood lactate concentrations, and blood gases were determined during exercise. Additionally baroreflex sensitivity, hypoxic and hypercapnic ventilatory response were determined before and after IHE. Hypoxic ventilatory response was increased after IHE (p<0.05. There were no altitude-dependent changes by IHE in any of the determined parameters. However, blood lactate concentrations and carbon dioxide output were reduced; minute ventilation and arterial oxygen saturation were unchanged, and ventilatory equivalent for carbon dioxide was increased after IHE irrespective of altitude. Changes in hypoxic ventilatory response were associated with changes in blood lactate (r = -0.72, p<0.05. Changes in blood lactate correlated with changes in carbon dioxide output (r = 0.61, p<0.01 and minute ventilation (r = 0.54, p<0.01. Based on the present results it seems that the reductions in blood lactate and carbon dioxide output have counteracted the increased hypoxic ventilatory response. As a result minute ventilation and arterial oxygen saturation did not increase during submaximal exercise at simulated altitudes between 2000 m and 4000 m.

  17. Caffeine counteracts impairments in task-oriented psychomotor performance induced by chlorpheniramine: a double-blind placebo-controlled crossover study.

    Science.gov (United States)

    Kim, Sung-Wan; Bae, Kyung-Yeol; Shin, Hee-Young; Kim, Jae-Min; Shin, Il-Seon; Kim, Jong-Keun; Kang, Gaeun; Yoon, Jin-Sang

    2013-01-01

    This study aimed to evaluate the effects of chlorpheniramine on psychomotor performance and the counteracting effects of caffeine on those sedative antihistamine actions. Sixteen healthy young men participated in this study. Using a double-blind placebo-controlled crossover design, each subject was administered one of the following conditions in a random order with a one-week interval: 'placebo-placebo', '4 mg of chlorpheniramine-placebo', 'placebo-200 mg of caffeine' or '4 mg of chlorpheniramine-200 mg of caffeine'. Before and after the treatments, psychomotor functions were assessed using a battery of tests. Additionally, subjective responses were assessed using a visual analogue scale (VAS). Psychomotor performance changed over time in different ways according to the combination of study medications. In the 'chlorpheniramine-placebo' condition, reaction times of the compensatory tracking task were significantly impaired compared with the other three conditions. In addition, the number of omission errors of the continuous performance test were significantly greater compared with the 'placebo-caffeine' condition. However, the response pattern of the 'chlorpheniramine-caffeine' condition was not significantly different from that of the 'placebo-placebo' condition. Changes of VAS for sleepiness were significantly greater in the 'chlorpheniramine-placebo' condition compared with the other three conditions. In conclusion, chlorpheniramine significantly increases subjective sleepiness and objectively impairs psychomotor performance. However, caffeine counteracts these sedative effects and psychomotor impairments.

  18. Housing, energy cost, and the poor: Counteracting effects in Germany's housing allowance program

    International Nuclear Information System (INIS)

    Groesche, Peter

    2010-01-01

    Adequate housing and affordable warmth are essential human needs, the lack of which may seriously harm people's health. Germany provides an allowance to low-income households, covering the housing as well as the space heating cost, to protect people from the consequences of poor housing conditions and fuel poverty. In order to limit public expenditures, payment recipients are required to choose low-cost dwellings, with the consequence that they probably occupy flats with a poor thermal performance. Recipients might therefore exhibit a lower per-square meter rent but in turn are likely to have a higher energy consumption and energy expenditures. Using a large data set of German households, this paper demonstrates that this financially counteracting effect is of negligible magnitude.

  19. Counteracting ammonia inhibition during anaerobic digestion by recovery using submersible microbial desalination cell

    DEFF Research Database (Denmark)

    Zhang, Yifeng; Angelidaki, Irini

    2015-01-01

    Ammonia inhibition is one of the most frequent and serious problems in biogas plants. In this study, a novel hybrid system consisting of a submersible microbial desalination cell (SMDC) and a continuous stirred tank reactor (CSTR) was developed for counteracting ammonia inhibition during anaerobic...... digestion (AD) with simultaneous in situ ammonia recovery and electricity production. The SMDC was powered by acetate in a buffer solution, while synthetic ammonia-rich wastewater was used as the feeding of the CSTR. Under continuous operation, ammonia recovery rate of 86 g-N/m2 /day and current density...... of 4.33 A/m2 were achieved at steady-state condition. As a result, 112% extra biogas was produced due to ammonia recovery by the SMDC. High-throughput sequencing showed that ammonia recovery had an impact on the microbial community structures in the SMDC and CSTR. Considering the additional economic...

  20. Stevioside counteracts the alpha cell hypersecretion caused by long-term palmitate exposure

    DEFF Research Database (Denmark)

    Hong, Jing; Chen, Jianguo; Jeppesen, Per Bendix

    2006-01-01

    Long-term exposure to fatty acids impairs beta-cell function in type 2 diabetes, but little is known about the chronic effects of fatty acids on alpha-cells. We therefore studied the prolonged impact of palmitate on alpha-cell function and on the expression of genes related to fuel metabolism. We......-activated receptor-gamma, and stearoyl-CoA desaturase gene expressions in the presence of palmitate (Pacids leads to a hypersecretion of glucagon and an accumulation of TG content in clonal alpha-TC1-6 cells. Stevioside was able to counteract the alpha......-cell hypersecretion caused by palmitate and enhanced the expression of genes involved in fatty acid metabolism. This indicates that stevioside may be a promising antidiabetic agent in treatment of type 2 diabetes....

  1. A Single Pair of Serotonergic Neurons Counteracts Serotonergic Inhibition of Ethanol Attraction in Drosophila.

    Science.gov (United States)

    Xu, Li; He, Jianzheng; Kaiser, Andrea; Gräber, Nikolas; Schläger, Laura; Ritze, Yvonne; Scholz, Henrike

    2016-01-01

    Attraction to ethanol is common in both flies and humans, but the neuromodulatory mechanisms underlying this innate attraction are not well understood. Here, we dissect the function of the key regulator of serotonin signaling-the serotonin transporter-in innate olfactory attraction to ethanol in Drosophila melanogaster. We generated a mutated version of the serotonin transporter that prolongs serotonin signaling in the synaptic cleft and is targeted via the Gal4 system to different sets of serotonergic neurons. We identified four serotonergic neurons that inhibit the olfactory attraction to ethanol and two additional neurons that counteract this inhibition by strengthening olfactory information. Our results reveal that compensation can occur on the circuit level and that serotonin has a bidirectional function in modulating the innate attraction to ethanol. Given the evolutionarily conserved nature of the serotonin transporter and serotonin, the bidirectional serotonergic mechanisms delineate a basic principle for how random behavior is switched into targeted approach behavior.

  2. In vitro generation of polysialylated cervical mucins by bacterial polysialyltransferases to counteract cytotoxicity of extracellular histones.

    Science.gov (United States)

    Galuska, Sebastian P; Galuska, Christina E; Tharmalingam, Tharmala; Zlatina, Kristina; Prem, Gerlinde; Husejnov, Farzali C O; Rudd, Pauline M; Vann, Willie F; Reid, Colm; Vionnet, Justine; Gallagher, Mary E; Carrington, Faye A; Hassett, Sarah-Louise; Carrington, Stephen D

    2017-06-01

    Neutrophil extracellular traps (NET) are formed against pathogens. However, various diseases are directly linked to this meshwork of DNA. The cytotoxic properties of extracellular histones especially seem to be an important trigger during these diseases. Furthermore, NET accumulation on implants is discussed to result in an impaired efficiency or failure, depending on the category of implant. Interestingly, mucins have been investigated as surface coatings potentially capable of reducing neutrophil adhesion. Similarly, polysialic acid was shown to inactivate the cytotoxic properties of extracellular histones. We wanted to combine the probability to decrease the adhesion of neutrophils using mucins with the capability of sialic acid polymers to counteract histone-mediated cytotoxicity. To this end, we elongate cervical mucins using bacterial polysialyltransferases. Subsequent cell-based experiments demonstrated the activity of elongated mucins against histone-mediated cytotoxicity. Thus, polysialylated mucins may represent a novel component to coat implants or to combat diseases with exaggerated NET formation. © 2017 Federation of European Biochemical Societies.

  3. Feline Immunodeficiency Virus Vif N-Terminal Residues Selectively Counteract Feline APOBEC3s.

    Science.gov (United States)

    Gu, Qinyong; Zhang, Zeli; Cano Ortiz, Lucía; Franco, Ana Cláudia; Häussinger, Dieter; Münk, Carsten

    2016-12-01

    Feline immunodeficiency virus (FIV) Vif protein counteracts feline APOBEC3s (FcaA3s) restriction factors by inducing their proteasomal degradation. The functional domains in FIV Vif for interaction with FcaA3s are poorly understood. Here, we have identified several motifs in FIV Vif that are important for selective degradation of different FcaA3s. Cats (Felis catus) express three types of A3s: single-domain A3Z2, single-domain A3Z3, and double-domain A3Z2Z3. We proposed that FIV Vif would selectively interact with the Z2 and the Z3 A3s. Indeed, we identified two N-terminal Vif motifs (12LF13 and 18GG19) that specifically interacted with the FcaA3Z2 protein but not with A3Z3. In contrast, the exclusive degradation of FcaA3Z3 was regulated by a region of three residues (M24, L25, and I27). Only a FIV Vif carrying a combination of mutations from both interaction sites lost the capacity to degrade and counteract FcaA3Z2Z3. However, alterations in the specific A3s interaction sites did not affect the cellular localization of the FIV Vif protein and binding to feline A3s. Pulldown experiments demonstrated that the A3 binding region localized to FIV Vif residues 50 to 80, outside the specific A3 interaction domain. Finally, we found that the Vif sites specific to individual A3s are conserved in several FIV lineages of domestic cat and nondomestic cats, while being absent in the FIV Vif of pumas. Our data support a complex model of multiple Vif-A3 interactions in which the specific region for selective A3 counteraction is discrete from a general A3 binding domain. Both human immunodeficiency virus (HIV) and feline immunodeficiency virus (FIV) Vif proteins counteract their host's APOBEC3 restriction factors. However, these two Vif proteins have limited sequence homology. The molecular interaction between FIV Vif and feline APOBEC3s are not well understood. Here, we identified N-terminal FIV Vif sites that regulate the selective interaction of Vif with either feline APOBEC3Z

  4. Malaysian adolescent students' needs for enhancing thinking skills, counteracting risk factors and demonstrating academic resilience

    Science.gov (United States)

    Kuldas, Seffetullah; Hashim, Shahabuddin; Ismail, Hairul Nizam

    2015-01-01

    The adolescence period of life comes along with changes and challenges in terms of physical and cognitive development. In this hectic period, many adolescents may suffer more from various risk factors such as low socioeconomic status, substance abuse, sexual abuse and teenage pregnancy. Findings indicate that such disadvantaged backgrounds of Malaysian adolescent students lead to failure or underachievement in their academic performance. This narrative review scrutinises how some of these students are able to demonstrate academic resilience, which is satisfactory performance in cognitive or academic tasks in spite of their disadvantaged backgrounds. The review stresses the need for developing a caregiving relationship model for at-risk adolescent students in Malaysia. Such a model would allow educators to meet the students' needs for enhancing thinking skills, counteracting risk factors and demonstrating academic resilience. PMID:25663734

  5. Nilotinib Enhances Tumor Angiogenesis and Counteracts VEGFR2 Blockade in an Orthotopic Breast Cancer Xenograft Model with Desmoplastic Response

    Directory of Open Access Journals (Sweden)

    Sara Zafarnia

    2017-11-01

    Full Text Available Vascular endothelial growth factor (VEGF/VEGF receptor (VEGFR-targeted therapies predominantly affect nascent, immature tumor vessels. Since platelet-derived growth factor receptor (PDGFR blockade inhibits vessel maturation and thus increases the amount of immature tumor vessels, we evaluated whether the combined PDGFR inhibition by nilotinib and VEGFR2 blockade by DC101 has synergistic therapy effects in a desmoplastic breast cancer xenograft model. In this context, besides immunohistological evaluation, molecular ultrasound imaging with BR55, the clinically used VEGFR2-targeted microbubbles, was applied to monitor VEGFR2-positive vessels noninvasively and to assess the therapy effects on tumor angiogenesis. DC101 treatment alone inhibited tumor angiogenesis, resulting in lower tumor growth and in significantly lower vessel density than in the control group after 14 days of therapy. In contrast, nilotinib inhibited vessel maturation but enhanced VEGFR2 expression, leading to markedly increased tumor volumes and a significantly higher vessel density. The combination of both drugs led to an almost similar tumor growth as in the DC101 treatment group, but VEGFR2 expression and microvessel density were higher and comparable to the controls. Further analyses revealed significantly higher levels of tumor cell–derived VEGF in nilotinib-treated tumors. In line with this, nilotinib, especially in low doses, induced an upregulation of VEGF and IL-6 mRNA in the tumor cells in vitro, thus providing an explanation for the enhanced angiogenesis observed in nilotinib-treated tumors in vivo. These findings suggest that nilotinib inhibits vessel maturation but counteracts the effects of antiangiogenic co-therapy by enhancing VEGF expression by the tumor cells and stimulating tumor angiogenesis.

  6. Identification of an unintended consequence of Nrf2-directed cytoprotection against a key tobacco carcinogen plus a counteracting chemopreventive intervention

    Science.gov (United States)

    Paonessa, Joseph D.; Ding, Yi; Randall, Kristen L.; Munday, Rex; Argoti, Dayana; Vouros, Paul; Zhang, Yuesheng

    2011-01-01

    Nrf2 is a major cytoprotective gene and is a key chemopreventive target against cancer and other diseases. Here we show that Nrf2 faces a dilemma in defense against 4-aminobiphenyl (ABP), a major human bladder carcinogen from tobacco smoke and other environmental sources. While Nrf2 protected mouse liver against ABP (which is metabolically activated in liver), the bladder level of N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP), the predominant ABP-DNA adduct formed in bladder cells and tissues, was markedly higher in Nrf2+/+ mice than in Nrf2−/− mice after ABP exposure. Notably, Nrf2 protected bladder cells against ABP in vitro. Mechanistic investigations showed that the dichotomous effects of Nrf2 could be explained at least partly by upregulation of UDP-glucuronosyltransferase (UGT). Nrf2 promoted conjugation of ABP with glucuronic acid in the liver, increasing urinary excretion of the conjugate. While glucuronidation of ABP and its metabolites is a detoxification process, these conjugates, which are excreted in urine, are known to be unstable in acidic urine, leading to delivery of the parent compounds to bladder. Hence, while higher liver UGT activity may protect the liver against ABP it increases bladder exposure to ABP. These findings raise concerns of potential bladder toxicity when Nrf2-activating chemopreventive agents are used in humans exposed to ABP, especially in smokers. We further demonstrate that 5,6-dihydrocyclopenta[c][1,2]-dithiole-3(4H)-thione (CPDT) significantly inhibits dG-C8-ABP formation in bladder cells and tissues, but does not appear to significantly modulate ABP-catalyzing UGT in liver. Thus, CPDT exemplifies a counteracting solution to the dilemma posed by Nrf2. PMID:21487034

  7. Maintenance of lettuce seed viability and counter-action of radiation damage by moisture equilibration-drying treatment

    International Nuclear Information System (INIS)

    Punjabi, Bina; Basu, R.N.

    1982-01-01

    Lettuce seeds were subjected to X- and gamma-radiation after moisture equilibration-drying or they were equilibrated with a saturated atmosphere for 24 hrs immediately after irradiation followed by drying back to the original weight. Results showed that moisture-equilibration drying treatment either before or after irradiation counteracts the adverse effects of irradiation. (M.G.B.)

  8. Maintenance of lettuce seed viability and counter-action of radiation damage by moisture equilibration-drying treatment

    Energy Technology Data Exchange (ETDEWEB)

    Punjabi, B; Basu, R N

    1982-10-01

    Lettuce seeds were subjected to X- and gamma-radiation after moisture equilibration-drying or they were equilibrated with a saturated atmosphere for 24 hrs immediately after irradiation followed by drying back to the original weight. Results showed that moisture-equilibration drying treatment either before or after irradiation counteracts the adverse effects of irradiation. (M.G.B.). 14 refs.

  9. Moderate consumption of beer, red wine and spirits has counteracting effects on plasma antioxidants in middle-aged men.

    Science.gov (United States)

    van der Gaag, M S; van den Berg, R; van den Berg, H; Schaafsma, G; Hendriks, H F

    2000-07-01

    To evaluate the in vivo effects of moderate consumption of red wine, beer and spirits on antioxidants, antioxidant enzymes and antioxidant capacity. Randomized, diet-controlled, cross-over study. Twelve apparently healthy, non-smoking middle-aged men were included; 11 of them completed the study. Each subject consumed four glasses of red wine, beer, spirits and water (negative control) with evening dinner during four successive periods of 3 weeks, daily at the Institute. The total diet was supplied to the subjects and had essential the same composition during these 12 weeks. Neither the enzyme activities of serum glutathion peroxidase, erythrocyte glutathion reductase and superoxide dismutase nor the plasma concentrations of alpha- and gamma-tocopherol, lutein, zeaxantin, beta-cryptoxanthin, lycopene and alpha-carotene were affected. Plasma beta-carotene concentrations were decreased after 3 weeks' consumption of red wine, beer and spirits (40 g alcohol/day) as compared to consumption of water, by 15% (P=0.0005), 11% (P=0.010) and 13% (P=0.003), respectively. Also, plasma ascorbic acid was decreased after beer (15%, P=0.004) and spirits (12%, P=0.030), but not after wine consumption. Serum uric acid concentrations were increased after consumption of beer (15%, Pspirits (8%, P=0.008) and red wine (9%, P=0.003). The overall serum antioxidant capacity, assessed as Trolox equivalent antioxidant capacity (TEAC), was similar for all treatments. Moderate consumption of red wine, beer and spirits has counteracting effects on plasma antioxidant components, resulting in no significant effect on overall antioxidant status. The effects on antioxidant parameters are largely independent of the type of alcoholic beverage, and probably irrelevant to chronic disease risk. Dutch Foundation for Alcohol Research (SAR).

  10. Therapeutic dosages of aspirin counteract the IL-6 induced pro-tumorigenic effects by slowing down the ribosome biogenesis rate

    Science.gov (United States)

    Brighenti, Elisa; Giannone, Ferdinando Antonino; Fornari, Francesca; Onofrillo, Carmine; Govoni, Marzia; Montanaro, Lorenzo; Treré, Davide; Derenzini, Massimo

    2016-01-01

    Chronic inflammation is a risk factor for the onset of cancer and the regular use of aspirin reduces the risk of cancer development. Here we showed that therapeutic dosages of aspirin counteract the pro-tumorigenic effects of the inflammatory cytokine interleukin(IL)-6 in cancer and non-cancer cell lines, and in mouse liver in vivo. We found that therapeutic dosages of aspirin prevented IL-6 from inducing the down-regulation of p53 expression and the acquisition of the epithelial mesenchymal transition (EMT) phenotypic changes in the cell lines. This was the result of a reduction in c-Myc mRNA transcription which was responsible for a down-regulation of the ribosomal protein S6 expression which, in turn, slowed down the rRNA maturation process, thus reducing the ribosome biogenesis rate. The perturbation of ribosome biogenesis hindered the Mdm2-mediated proteasomal degradation of p53, throughout the ribosomal protein-Mdm2-p53 pathway. P53 stabilization hindered the IL-6 induction of the EMT changes. The same effects were observed in livers from mice stimulated with IL-6 and treated with aspirin. It is worth noting that aspirin down-regulated ribosome biogenesis, stabilized p53 and up-regulated E-cadherin expression in unstimulated control cells also. In conclusion, these data showed that therapeutic dosages of aspirin increase the p53-mediated tumor-suppressor activity of the cells thus being in this way able to reduce the risk of cancer onset, either or not linked to chronic inflammatory processes. PMID:27557515

  11. Therapeutic dosages of aspirin counteract the IL-6 induced pro-tumorigenic effects by slowing down the ribosome biogenesis rate.

    Science.gov (United States)

    Brighenti, Elisa; Giannone, Ferdinando Antonino; Fornari, Francesca; Onofrillo, Carmine; Govoni, Marzia; Montanaro, Lorenzo; Treré, Davide; Derenzini, Massimo

    2016-09-27

    Chronic inflammation is a risk factor for the onset of cancer and the regular use of aspirin reduces the risk of cancer development. Here we showed that therapeutic dosages of aspirin counteract the pro-tumorigenic effects of the inflammatory cytokine interleukin(IL)-6 in cancer and non-cancer cell lines, and in mouse liver in vivo. We found that therapeutic dosages of aspirin prevented IL-6 from inducing the down-regulation of p53 expression and the acquisition of the epithelial mesenchymal transition (EMT) phenotypic changes in the cell lines. This was the result of a reduction in c-Myc mRNA transcription which was responsible for a down-regulation of the ribosomal protein S6 expression which, in turn, slowed down the rRNA maturation process, thus reducing the ribosome biogenesis rate. The perturbation of ribosome biogenesis hindered the Mdm2-mediated proteasomal degradation of p53, throughout the ribosomal protein-Mdm2-p53 pathway. P53 stabilization hindered the IL-6 induction of the EMT changes. The same effects were observed in livers from mice stimulated with IL-6 and treated with aspirin. It is worth noting that aspirin down-regulated ribosome biogenesis, stabilized p53 and up-regulated E-cadherin expression in unstimulated control cells also. In conclusion, these data showed that therapeutic dosages of aspirin increase the p53-mediated tumor-suppressor activity of the cells thus being in this way able to reduce the risk of cancer onset, either or not linked to chronic inflammatory processes.

  12. Prevalence and effects of mycotoxins on poultry health and performance, and recent development in mycotoxin counteracting strategies.

    Science.gov (United States)

    Murugesan, G R; Ledoux, D R; Naehrer, K; Berthiller, F; Applegate, T J; Grenier, B; Phillips, T D; Schatzmayr, G

    2015-06-01

    Extensive research over the last couple of decades has made it obvious that mycotoxins are commonly prevalent in majority of feed ingredients. A worldwide mycotoxin survey in 2013 revealed 81% of around 3,000 grain and feed samples analyzed had at least 1 mycotoxin, which was higher than the 10-year average (from 2004 to 2013) of 76% in a total of 25,944 samples. The considerable increase in the number of positive samples in 2013 may be due to the improvements in detection methods and their sensitivity. The recently developed liquid chromatography coupled to (tandem) mass spectrometry allows the inclusion of a high number of analytes and is the most selective, sensitive, and accurate of all the mycotoxin analytical methods. Mycotoxins can affect the animals either individually or additively in the presence of more than 1 mycotoxin, and may affect various organs such as gastrointestinal tract, liver, and immune system, essentially resulting in reduced productivity of the birds and mortality in extreme cases. While the use of mycotoxin binding agents has been a commonly used counteracting strategy, considering the great diversity in the chemical structures of mycotoxins, it is very obvious that there is no single method that can be used to deactivate mycotoxins in feed. Therefore, different strategies have to be combined in order to specifically target individual mycotoxins without impacting the quality of feed. Enzymatic or microbial detoxification, referred to as "biotransformation" or "biodetoxification," utilizes microorganisms or purified enzymes thereof to catabolize the entire mycotoxin or transform or cleave it to less or non-toxic compounds. However, the awareness on the prevalence of mycotoxins, available modern techniques to analyze them, the effects of mycotoxicoses, and the recent developments in the ways to safely eliminate the mycotoxins from the feed are very minimal among the producers. This symposium review paper comprehensively discusses the above

  13. Prevalence and effects of mycotoxins on poultry health and performance, and recent development in mycotoxin counteracting strategies1

    Science.gov (United States)

    Murugesan, G. R.; Ledoux, D. R.; Naehrer, K.; Berthiller, F.; Applegate, T. J.; Grenier, B.; Phillips, T. D.; Schatzmayr, G.

    2015-01-01

    Extensive research over the last couple of decades has made it obvious that mycotoxins are commonly prevalent in majority of feed ingredients. A worldwide mycotoxin survey in 2013 revealed 81% of around 3,000 grain and feed samples analyzed had at least 1 mycotoxin, which was higher than the 10-year average (from 2004 to 2013) of 76% in a total of 25,944 samples. The considerable increase in the number of positive samples in 2013 may be due to the improvements in detection methods and their sensitivity. The recently developed liquid chromatography coupled to (tandem) mass spectrometry allows the inclusion of a high number of analytes and is the most selective, sensitive, and accurate of all the mycotoxin analytical methods. Mycotoxins can affect the animals either individually or additively in the presence of more than 1 mycotoxin, and may affect various organs such as gastrointestinal tract, liver, and immune system, essentially resulting in reduced productivity of the birds and mortality in extreme cases. While the use of mycotoxin binding agents has been a commonly used counteracting strategy, considering the great diversity in the chemical structures of mycotoxins, it is very obvious that there is no single method that can be used to deactivate mycotoxins in feed. Therefore, different strategies have to be combined in order to specifically target individual mycotoxins without impacting the quality of feed. Enzymatic or microbial detoxification, referred to as “biotransformation” or “biodetoxification,” utilizes microorganisms or purified enzymes thereof to catabolize the entire mycotoxin or transform or cleave it to less or non-toxic compounds. However, the awareness on the prevalence of mycotoxins, available modern techniques to analyze them, the effects of mycotoxicoses, and the recent developments in the ways to safely eliminate the mycotoxins from the feed are very minimal among the producers. This symposium review paper comprehensively discusses

  14. National Nuclear Center of the Republic of Kazakhstan in the system of nuclear terrorism counteractions at Kazakhstan territory

    International Nuclear Information System (INIS)

    Tukhvatulin, Sh.T.; Zhotabayev, Zh.R.; Azarov, V.A.; Silayev, M.E.

    2002-01-01

    authorities and reduction of their power and capabilities, a general threat of terrorist acts at companies using nuclear and radiation technologies has increased. In addition, due to its geographical position, the Republic of Kazakhstan is a transit state between Europe and Asia. That is why, numerous cases of transit shipment and sale attempts of nuclear materials from other states including the former SU republics were recorded here (e.g., fuel elements from Chernobyl NPP). The above demonstrates an unprejudiced necessity of arranging an efficient counteraction system against nuclear terrorism in the Republic of Kazakhstan. The current Kazakhstan system of nuclear and radioactive materials control does not meet the present-day requirements. Its efficiency and capabilities should obviously be increased. This will allow avoiding considerable losses by existing economical figures and potential political losses in the international relations. After collapse of the Soviet Union, major nuclear research institutions and branches left at the territory of independent Kazakhstan were consolidated into a uniform organization: the Republican State Enterprise National Nuclear Center of the Republic of Kazakhstan. At present, four institutions are functioning under the aegis of the Center. By this time, many directions of the Center activity are related or contribute to potential nuclear terrorism counteractions. Among the wide range of these activities, the major ones are worth mentioning, both performed and in process: The project on elimination of the last nuclear device at the former Semipalatinsk Test-Site territory; The projects on weapons of mass destruction infrastructure elimination. In particular, projects related to closure and permanent sealing of defense tunnels used and prepared for nuclear weapon testing; The project on irreversible shut-down and decommissioning with following long-term conservation of BN-350 fast power reactor in Aktau; The project on the high plutonium

  15. Positive Alpha and Negative Beta (A Strategy for Counteracting Systematic Risk

    Directory of Open Access Journals (Sweden)

    Erik Sonne Noddeboe

    2015-09-01

    Full Text Available Undiversifiable (or systematic risk has long been an enemy of investors. Many countercyclical strategies have been developed to counter this. However, like all insurance types, these strategies are generally costly to implement, and over time can significantly reduce portfolio returns in long and extended bull markets. In this paper, we discuss an alternative technique, founded on the premise of physiological bias and risk-aversion. We take a behavioral discussion in order to contextualize the insurance like characteristics of option pricing and discuss how this can lead to a mispricing of the asymmetric relationship between the VIX and the S&P 500. To test this, we perform studies in which we find statistical inefficiencies, thereby making it possible to implement a method of hedging index option premium in a way that has displayed no monthly drawdowns in bullish periods, while still providing large returns in major sell-offs. The three versions of the strategy discussed have negative betas to the S&P 500, while exhibiting similar risk-adjusted excess returns over both bull and bear markets. Further, the performance generated over the entire period, for all three strategies, is highly statistically significant. The results challenge the weak form of the Efficient Market Hypothesis and provide evidence that the methods of hedging could be a valuable addition to an equity rich portfolio for the purpose of counteracting systematic risk.

  16. HSV-1 ICP0: An E3 Ubiquitin Ligase That Counteracts Host Intrinsic and Innate Immunity

    Directory of Open Access Journals (Sweden)

    Mirna Perusina Lanfranca

    2014-05-01

    Full Text Available The herpes simplex virus type 1 (HSV-1 encoded E3 ubiquitin ligase, infected cell protein 0 (ICP0, is required for efficient lytic viral replication and regulates the switch between the lytic and latent states of HSV-1. As an E3 ubiquitin ligase, ICP0 directs the proteasomal degradation of several cellular targets, allowing the virus to counteract different cellular intrinsic and innate immune responses. In this review, we will focus on how ICP0’s E3 ubiquitin ligase activity inactivates the host intrinsic defenses, such as nuclear domain 10 (ND10, SUMO, and the DNA damage response to HSV-1 infection. In addition, we will examine ICP0’s capacity to impair the activation of interferon (innate regulatory mediators that include IFI16 (IFN γ-inducible protein 16, MyD88 (myeloid differentiation factor 88, and Mal (MyD88 adaptor-like protein. We will also consider how ICP0 allows HSV-1 to evade activation of the NF-κB (nuclear factor kappa B inflammatory signaling pathway. Finally, ICP0’s paradoxical relationship with USP7 (ubiquitin specific protease 7 and its roles in intrinsic and innate immune responses to HSV-1 infection will be discussed.

  17. Counteracting ammonia inhibition during anaerobic digestion by recovery using submersible microbial desalination cell.

    Science.gov (United States)

    Zhang, Yifeng; Angelidaki, Irini

    2015-07-01

    Ammonia inhibition is one of the most frequent and serious problems in biogas plants. In this study, a novel hybrid system consisting of a submersible microbial desalination cell (SMDC) and a continuous stirred tank reactor (CSTR) was developed for counteracting ammonia inhibition during anaerobic digestion (AD) with simultaneous in situ ammonia recovery and electricity production. The SMDC was powered by acetate in a buffer solution, while synthetic ammonia-rich wastewater was used as the feeding of the CSTR. Under continuous operation, ammonia recovery rate of 86 g-N/m(2) /day and current density of 4.33 A/m(2) were achieved at steady-state condition. As a result, 112% extra biogas was produced due to ammonia recovery by the SMDC. High-throughput sequencing showed that ammonia recovery had an impact on the microbial community structures in the SMDC and CSTR. Considering the additional economic benefits of biogas enhancement and possible wastewater treatment, the SMDC may represent a cost-effective and environmentally friendly method for waste resources recovery and biomethanation of ammonia-rich residues. © 2015 Wiley Periodicals, Inc.

  18. Counteracting Rotor Imbalance in a Bearingless Motor System with Feedforward Control

    Science.gov (United States)

    Kascak, Peter Eugene; Jansen, Ralph H.; Dever, Timothy; Nagorny, Aleksandr; Loparo, Kenneth

    2012-01-01

    In standard motor applications, traditional mechanical bearings represent the most economical approach to rotor suspension. However, in certain high performance applications, rotor suspension without bearing contact is either required or highly beneficial. Such applications include very high speed, extreme environment, or limited maintenance access applications. This paper extends upon a novel bearingless motor concept, in which full five-axis levitation and rotation of the rotor is achieved using two motors with opposing conical air-gaps. By leaving the motors' pole-pairs unconnected, different d-axis flux in each pole-pair is created, generating a flux imbalance which creates lateral force. Note this is approach is different than that used in previous bearingless motors, which use separate windings for levitation and rotation. This paper will examine the use of feedforward control to counteract synchronous whirl caused by rotor imbalance. Experimental results will be presented showing the performance of a prototype bearingless system, which was sized for a high speed flywheel energy storage application, with and without feedforward control.

  19. Protein Phosphatase 1 Recruitment by Rif1 Regulates DNA Replication Origin Firing by Counteracting DDK Activity

    Directory of Open Access Journals (Sweden)

    Anoushka Davé

    2014-04-01

    Full Text Available The firing of eukaryotic origins of DNA replication requires CDK and DDK kinase activities. DDK, in particular, is involved in setting the temporal program of origin activation, a conserved feature of eukaryotes. Rif1, originally identified as a telomeric protein, was recently implicated in specifying replication timing in yeast and mammals. We show that this function of Rif1 depends on its interaction with PP1 phosphatases. Mutations of two PP1 docking motifs in Rif1 lead to early replication of telomeres in budding yeast and misregulation of origin firing in fission yeast. Several lines of evidence indicate that Rif1/PP1 counteract DDK activity on the replicative MCM helicase. Our data suggest that the PP1/Rif1 interaction is downregulated by the phosphorylation of Rif1, most likely by CDK/DDK. These findings elucidate the mechanism of action of Rif1 in the control of DNA replication and demonstrate a role of PP1 phosphatases in the regulation of origin firing.

  20. FGFR2-Driven Signaling Counteracts Tamoxifen Effect on ERα-Positive Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Lukasz Turczyk

    2017-10-01

    Full Text Available Signaling mediated by growth factors receptors has long been suggested as one of the key factors responsible for failure of endocrine treatment in breast cancer (BCa. Herein we present that in the presence of tamoxifen, FGFs (Fibroblast Growth Factors promote BCa cell growth with the strongest effect being produced by FGF7. FGFR2 was identified as a mediator of FGF7 action and the FGFR2-induced signaling was found to underlie cancer-associated fibroblasts-dependent resistance to tamoxifen. FGF7/FGFR2-triggered pathway was shown to induce ER phosphorylation, ubiquitination and subsequent ER proteasomal degradation which counteracted tamoxifen-promoted ER stabilization. We also identified activation of PI3K/AKT signaling targeting ER-Ser167 and regulation of Bcl-2 expression as a mediator of FGFR2-promoted resistance to tamoxifen. Analysis of tissue samples from patients with invasive ductal carcinoma revealed an inversed correlation between expression of FGFR2 and ER, thus supporting our in vitro data. These results unveil the complexity of ER regulation by FGFR2-mediated signaling likely to be associated with BCa resistance to endocrine therapy.

  1. Clomipramine counteracts lipid raft disturbance due to short-term muscle disuse.

    Science.gov (United States)

    Bryndina, Irina G; Shalagina, Maria N; Sekunov, Alexey V; Zefirov, Andrei L; Petrov, Alexey M

    2018-01-18

    Disuse-induced skeletal muscle dysfunction is a serious consequence of long-term spaceflight, numerous diseases and conditions for which treatment possibilities are still strictly limited. We have previously shown that acute hindlimb suspension (HS)-mediated disuse disrupts membrane lipid rafts in the unloaded muscle. Here, we investigated whether pretreatment of rats with the inhibitor of acid sphingomyelinase, clomipramine (1.25mg/g/day, intramuscularly, for 5days before HS), is able to hinder the loss in lipid raft integrity in response to 12h of HS. Clomipramine pretreatment significantly counteracted the decrease in labeling of the plasma membranes with lipid raft markers (fluorescent cholera toxin B subunit and bodipy-GM1-ganglioside) specifically in the junctional regions of the suspended soleus muscle. This was associated with: a) enhancing raft disrupting potential of exogenous sphingomyelinase in the junctional membranes; b) prevention of both ceramide accumulation and cholesterol loss; c) prevention of decline in nicotinic acetylcholine receptor labeling in the unloaded muscle. Our data suggest that sphingomyelinase-mediated raft disturbance serves as one of the earlier events in HS effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Apricot melanoidins prevent oxidative endothelial cell death by counteracting mitochondrial oxidation and membrane depolarization.

    Directory of Open Access Journals (Sweden)

    Annalisa Cossu

    Full Text Available The cardiovascular benefits associated with diets rich in fruit and vegetables are thought to be due to phytochemicals contained in fresh plant material. However, whether processed plant foods provide the same benefits as unprocessed ones is an open question. Melanoidins from heat-processed apricots were isolated and their presence confirmed by colorimetric analysis and browning index. Oxidative injury of endothelial cells (ECs is the key step for the onset and progression of cardiovascular diseases (CVD, therefore the potential protective effect of apricot melanoidins on hydrogen peroxide-induced oxidative mitochondrial damage and cell death was explored in human ECs. The redox state of cytoplasmic and mitochondrial compartments was detected by using the redox-sensitive, fluorescent protein (roGFP, while the mitochondrial membrane potential (MMP was assessed with the fluorescent dye, JC-1. ECs exposure to hydrogen peroxide, dose-dependently induced mitochondrial and cytoplasmic oxidation. Additionally detected hydrogen peroxide-induced phenomena were MMP dissipation and ECs death. Pretreatment of ECs with apricot melanoidins, significantly counteracted and ultimately abolished hydrogen peroxide-induced intracellular oxidation, mitochondrial depolarization and cell death. In this regard, our current results clearly indicate that melanoidins derived from heat-processed apricots, protect human ECs against oxidative stress.

  3. Personal values that support and counteract utilization of a screening test for prostate cancer.

    Science.gov (United States)

    Aavik, Toivo; Aavik, Anu; Punab, Margus

    2014-01-01

    The main aim of the current research was to discover the personal values that may support men's prostate cancer screening decisions in the future. We asked for participants' past behavior and future behavioral intentions, and also considered their real-life behavior. The sample consisted of 371 men, of which 93 were first-time patients at the Andrology Unit. The results show that Security value was related to past participation, while Achievement, Stimulation, and Traditions counteracted this. Present prostate-testing behavior was related only to higher Security values. Predictors of future behavioral intentions were Security, Self-direction, and Benevolence, which described 21% of the total variability. Considering informed decision-making processes, our results suggest that men who hold Security, Self-direction, and Benevolence values are more likely to participate in office-based initial screening. The study indicates the need to offer office-based initial screening to those age-eligible men whose values do not support participation.

  4. MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate Neurogenesis

    Directory of Open Access Journals (Sweden)

    Francisca F. Vasconcelos

    2016-10-01

    Full Text Available The generation of neurons from neural stem cells requires large-scale changes in gene expression that are controlled to a large extent by proneural transcription factors, such as Ascl1. While recent studies have characterized the differentiation genes activated by proneural factors, less is known on the mechanisms that suppress progenitor cell identity. Here, we show that Ascl1 induces the transcription factor MyT1 while promoting neuronal differentiation. We combined functional studies of MyT1 during neurogenesis with the characterization of its transcriptional program. MyT1 binding is associated with repression of gene transcription in neural progenitor cells. It promotes neuronal differentiation by counteracting the inhibitory activity of Notch signaling at multiple levels, targeting the Notch1 receptor and many of its downstream targets. These include regulators of the neural progenitor program, such as Hes1, Sox2, Id3, and Olig1. Thus, Ascl1 suppresses Notch signaling cell-autonomously via MyT1, coupling neuronal differentiation with repression of the progenitor fate.

  5. Developing Tools to Counteract and Prevent Suicide Bomber Incidents: A Case Study in Value Sensitive Design.

    Science.gov (United States)

    Royakkers, Lambèr; Steen, Marc

    2017-08-01

    Developers and designers make all sorts of moral decisions throughout an innovation project. In this article, we describe how teams of developers and designers engaged with ethics in the early phases of innovation based on case studies in the SUBCOP project (SUBCOP stands for 'SUicide Bomber COunteraction and Prevention'). For that purpose, Value Sensitive Design (VSD) will be used as a reference. Specifically, we focus on the following two research questions: How can researchers/developers learn about users' perspectives and values during the innovation process? and How can researchers/developers take into account these values, and related design criteria, in their decision-making during the innovation process? Based on a case study of several innovation processes in this project, we conclude the researchers/developers involved are able to do something similar to VSD (without them knowing about VSD or calling it 'VSD'), supported by relatively simple exercises in the project, e.g., meetings with potential end-users and discussions with members of the Ethical Advisory Board of the project. Furthermore, we also found-possibly somewhat counterintuitively-that a commercial, with its focus on understanding and satisfying customers' needs, can promote VSD.

  6. RTEL1 dismantles T loops and counteracts telomeric G4-DNA to maintain telomere integrity.

    Science.gov (United States)

    Vannier, Jean-Baptiste; Pavicic-Kaltenbrunner, Visnja; Petalcorin, Mark I R; Ding, Hao; Boulton, Simon J

    2012-05-11

    T loops and telomeric G-quadruplex (G4) DNA structures pose a potential threat to genome stability and must be dismantled to permit efficient telomere replication. Here we implicate the helicase RTEL1 in the removal of telomeric DNA secondary structures, which is essential for preventing telomere fragility and loss. In the absence of RTEL1, T loops are inappropriately resolved by the SLX4 nuclease complex, resulting in loss of the telomere as a circle. Depleting SLX4 or blocking DNA replication abolished telomere circles (TCs) and rescued telomere loss in RTEL1(-/-) cells but failed to suppress telomere fragility. Conversely, stabilization of telomeric G4-DNA or loss of BLM dramatically enhanced telomere fragility in RTEL1-deficient cells but had no impact on TC formation or telomere loss. We propose that RTEL1 performs two distinct functions at telomeres: it disassembles T loops and also counteracts telomeric G4-DNA structures, which together ensure the dynamics and stability of the telomere. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Ursodeoxycholic acid counteracts celecoxib in reduction of duodenal polyps in patients with familial adenomatous polyposis: a multicentre, randomized controlled trial

    Science.gov (United States)

    2013-01-01

    Background Due to prophylactic colectomy, mortality in patients with familial adenomatous polyposis (FAP) has changed, with duodenal cancer currently being the main cause of death. Although celecoxib reduces duodenal polyp density in patients with FAP, its long-term use may increase the risk of cardiovascular events and alternatives need to be explored. Preclinical studies suggest that the combination of celecoxib with ursodeoxycholic acid (UDCA) is a potentially effective strategy. We performed a randomized, double-blind, placebo-controlled trial to investigate the effect of celecoxib and UDCA co-treatment on duodenal adenomatosis in patients with FAP. Methods Patients with FAP received celecoxib (400 mg twice daily) and UDCA (1000-2000 mg daily, ~20-30 mg/kg/day, n=19) or celecoxib and placebo (n=18) orally for 6 months. Primary outcome was drug efficacy, assessed by comparing duodenal polyp density at pre- and post-intervention by blinded review of endoscopic recordings. As secondary outcomes, cell proliferation, apoptosis, and COX-2 levels in normal duodenal mucosa were assessed by immunohistochemistry or real-time quantitative polymerase chain reaction. Results In intention-to-treat analysis, deceased polyp density was observed after celecoxib/placebo treatment (p=0.029), whereas increased polyp density was observed after celecoxib/UDCA treatment (p=0.014). The difference in change in duodenal polyp density was statistically significant between the groups (p=0.011). No changes in secondary outcomes were observed. Thirty patients (81%) reported one or more adverse events, 16 patients (84%, Common Toxicity Criteria for Adverse Events version 3.0 (CTCAE) grade 1–3) treated with celecoxib/UDCA and 14 patients (78%, CTCAE grade 1–2) treated with celecoxib/placebo. Nine patients (24%) discontinued intervention prematurely, 5 patients (26%) treated with celecoxib/UDCA and 4 patients (22%) treated with celecoxib/placebo. Conclusions Celecoxib reduces duodenal

  8. Counteracting ammonia inhibition in anaerobic digestion by removal with a hollow fiber membrane contactor.

    Science.gov (United States)

    Lauterböck, B; Ortner, M; Haider, R; Fuchs, W

    2012-10-01

    The aim of the current study was to investigate the feasibility of membrane contactors for continuous ammonia (NH₃-N) removal in an anaerobic digestion process and to counteract ammonia inhibition. Two laboratory anaerobic digesters were fed slaughterhouse wastes with ammonium (NH₄⁺) concentrations ranging from 6 to 7.4 g/L. One reactor was used as reference reactor without any ammonia removal. In the second reactor, a hollow fiber membrane contactor module was used for continuous ammonia removal. The hollow fiber membranes were directly submerged into the digestate of the anaerobic reactor. Sulfuric acid was circulated in the lumen as an adsorbent solution. Using this set up, the NH₄⁺-N concentration in the membrane reactor was significantly reduced. Moreover the extraction of ammonia lowered the pH by 0.2 units. In combination that led to a lowering of the free NH₃-N concentration by about 70%. Ammonia inhibition in the reference reactor was observed when the concentration exceeded 6 g/L NH₄⁺-N or 1-1.2 g/L NH₃-N. In contrast, in the membrane reactor the volatile fatty acid concentration, an indicator for process stability, was much lower and a higher gas yield and better degradation was observed. The chosen approach offers an appealing technology to remove ammonia directly from media having high concentrations of solids and it can help to improve process efficiency in anaerobic digestion of ammonia rich substrates. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Counteracting chemical chaperone effects on the single-molecule α-synuclein structural landscape.

    Science.gov (United States)

    Ferreon, Allan Chris M; Moosa, Mahdi Muhammad; Gambin, Yann; Deniz, Ashok A

    2012-10-30

    Protein structure and function depend on a close interplay between intrinsic folding energy landscapes and the chemistry of the protein environment. Osmolytes are small-molecule compounds that can act as chemical chaperones by altering the environment in a cellular context. Despite their importance, detailed studies on the role of these chemical chaperones in modulating structure and dimensions of intrinsically disordered proteins have been limited. Here, we used single-molecule Förster resonance energy transfer to test the counteraction hypothesis of counterbalancing effects between the protecting osmolyte trimethylamine-N-oxide (TMAO) and denaturing osmolyte urea for the case of α-synuclein, a Parkinson's disease-linked protein whose monomer exhibits significant disorder. The single-molecule experiments, which avoid complications from protein aggregation, do not exhibit clear solvent-induced cooperative protein transitions for these osmolytes, unlike results from previous studies on globular proteins. Our data demonstrate the ability of TMAO and urea to shift α-synuclein structures towards either more compact or expanded average dimensions. Strikingly, the experiments directly reveal that a 21 [urea][TMAO] ratio has a net neutral effect on the protein's dimensions, a result that holds regardless of the absolute osmolyte concentrations. Our findings shed light on a surprisingly simple aspect of the interplay between urea and TMAO on α-synuclein in the context of intrinsically disordered proteins, with potential implications for the biological roles of such chemical chaperones. The results also highlight the strengths of single-molecule experiments in directly probing the chemical physics of protein structure and disorder in more chemically complex environments.

  10. Counteracting chemical chaperone effects on the single-molecule α-synuclein structural landscape

    Science.gov (United States)

    Ferreon, Allan Chris M.; Moosa, Mahdi Muhammad; Deniz, Ashok A.

    2012-01-01

    Protein structure and function depend on a close interplay between intrinsic folding energy landscapes and the chemistry of the protein environment. Osmolytes are small-molecule compounds that can act as chemical chaperones by altering the environment in a cellular context. Despite their importance, detailed studies on the role of these chemical chaperones in modulating structure and dimensions of intrinsically disordered proteins have been limited. Here, we used single-molecule Förster resonance energy transfer to test the counteraction hypothesis of counterbalancing effects between the protecting osmolyte trimethylamine-N-oxide (TMAO) and denaturing osmolyte urea for the case of α-synuclein, a Parkinson’s disease-linked protein whose monomer exhibits significant disorder. The single-molecule experiments, which avoid complications from protein aggregation, do not exhibit clear solvent-induced cooperative protein transitions for these osmolytes, unlike results from previous studies on globular proteins. Our data demonstrate the ability of TMAO and urea to shift α-synuclein structures towards either more compact or expanded average dimensions. Strikingly, the experiments directly reveal that a 2∶1 [urea]∶[TMAO] ratio has a net neutral effect on the protein’s dimensions, a result that holds regardless of the absolute osmolyte concentrations. Our findings shed light on a surprisingly simple aspect of the interplay between urea and TMAO on α-synuclein in the context of intrinsically disordered proteins, with potential implications for the biological roles of such chemical chaperones. The results also highlight the strengths of single-molecule experiments in directly probing the chemical physics of protein structure and disorder in more chemically complex environments. PMID:22826265

  11. Quantum system under the actions of two counteracting baths: A model for the attenuation-amplification interplay

    International Nuclear Information System (INIS)

    Lorenzen, F.; Moussa, M. H. Y.; Ponte, M. A. de; Almeida, N. G. de

    2009-01-01

    We analyze the dynamical behavior of a quantum system under the actions of two counteracting baths: the inevitable energy draining reservoir and, in opposition, exciting the system, an engineered Glauber's amplifier. We follow the system dynamics towards equilibrium to map its distinctive behavior arising from the interplay of attenuation and amplification. Such a mapping, with the corresponding parameter regimes, is achieved by calculating the evolution of both the excitation and the Glauber-Sudarshan P function. Techniques to compute the decoherence and the fidelity of quantum states under the action of both counteracting baths, based on the Wigner function rather than the density matrix, are also presented. They enable us to analyze the similarity of the evolved state vector of the system with respect to the original one, for all regimes of parameters. Applications of this attenuation-amplification interplay are discussed.

  12. Action plan to counteract soil acidification and to promote sustainable use of forest land

    International Nuclear Information System (INIS)

    2002-04-01

    This report consists of the National Board of Forestry's proposals on a plan to counteract soil acidification and to promote sustainable use of forest land. In 1989 the government requested the National Board of Forestry to start experimental activities to find measures to counteract soil acidification. In 1997 the Board presented a proposal for liming and vitalisation of forest land. An Environmental Impact Assessment of the proposal was submitted in 1999, after which a revision of the plan was started. In order to obtain better basic knowledge of the situation, the Board of Forestry commissioned nine reports that dealt with different aspects of soil acidification and corrective measures. Major emphasis has also been placed on the national environmental quality goals and the national plan for liming of lakes and waterways. The report is divided into three parts. The first part explains the Board of Forestry's proposals on measures to counteract soil acidification, and the second part, the description of the situation today, presents the conditions for the design of the plan such as political goals and guidelines that affect the plan and its design, the knowledge available today on soil acidification, its effects, possibilities for recovery, and possible measures that can be used. The third and final part contains brief summaries of the responses to the plan when circulated for comments. The action plan allows a return of the buffering capacity of the most acidified forest land, mainly in southern and southwestern Sweden. The Board of Forestry proposes that the spreading of ashes and lime is done within drainage areas where the natural recovery is assessed to be slow and insufficient, and where the leaching of toxic aluminium from forest land is hazardous to the aquatic ecosystem. In the assessments made by the Board, between 200,000 and 350,000 hectares of forest land may require measures of this kind. The Board of Forestry is of the opinion that a three

  13. Modulation of Stem Cell Differentiation and Myostatin as an Approach to Counteract Fibrosis in Muscle Dystrophy and Regeneration after Injury

    Science.gov (United States)

    2011-03-01

    Duchenne muscular dystrophy (DMD). To examine whether counteracting myostatin, a negative regulator of muscle mass and a pro-lipofibrotic factor...extracellular matrix, and fat, characterizes muscle dystrophy , and in particular Duchenne muscular dystrophy (DMD) (1,2), as seen also in its animal model...stem cells (MDSC) into myogenic as opposed to lipofibrogenic lineages is a promising therapeutic strategy for Duchenne muscular dystrophy (DMD). To

  14. Counteraction of urea-induced protein denaturation by trimethylamine N-oxide: A chemical chaperone at atomic resolution

    OpenAIRE

    Bennion, Brian J.; Daggett, Valerie

    2004-01-01

    Proteins are very sensitive to their solvent environments. Urea is a common chemical denaturant of proteins, yet some animals contain high concentrations of urea. These animals have evolved an interesting mechanism to counteract the effects of urea by using trimethylamine N-oxide (TMAO). The molecular basis for the ability of TMAO to act as a chemical chaperone remains unknown. Here, we describe molecular dynamics simulations of a small globular protein, chymotrypsin inhibitor 2, in 8 M urea ...

  15. Success Counteracting Tobacco Company Interference in Thailand: An Example of FCTC Implementation for Low- and Middle-income Countries

    Directory of Open Access Journals (Sweden)

    Stephen L. Hamann

    2012-03-01

    Full Text Available Transnational tobacco companies (TTCs interfere regularly in policymaking in low- and middle-income countries (LMICs. The WHO Framework Convention for Tobacco Control provides mechanisms and guidance for dealing with TTC interference, but many countries still face ‘how to’ challenges of implementation. For more than two decades, Thailand’s public health community has been developing a system for identifying and counteracting strategies TTCs use to derail, delay and undermine tobacco control policymaking. Consequently, Thailand has already implemented most of the FCTC guidelines for counteracting TTC interference. In this study, our aims are to describe strategies TTCs have used in Thailand to interfere in policymaking, and to examine how the public health community in Thailand has counteracted TTC interference. We analyzed information reported by three groups with a stake in tobacco control policies: Thai tobacco control advocates, TTCs, and international tobacco control experts. To identify TTC viewpoints and strategies, we also extracted information from internal tobacco industry documents. We synthesized these data and identified six core strategies TTCs use to interfere in tobacco control policymaking: (1 doing business with ‘two faces’, (2 seeking to influence people in high places, (3 ‘buying’ advocates in grassroots organizations, (4 putting up a deceptive front, (5 intimidation, and (6 undermining controls on tobacco advertising, promotion and sponsorship. We present three case examples showing where TTCs have employed multiple interference strategies simultaneously, and showing how Thai tobacco control advocates have successfully counteracted those strategies by: (1 conducting vigilant surveillance, (2 excluding tobacco companies from policymaking, (3 restricting tobacco company sales, (4 sustaining pressure, and (5 dedicating resources to the effective enforcement of regulations. Policy implications from this study are

  16. Announced reward counteracts the effects of chronic social stress on anticipatory behavior and hippocampal synaptic plasticity in rats.

    Science.gov (United States)

    Kamal, Amer; Van der Harst, Johanneke E; Kapteijn, Chantal M; Baars, Annemarie J M; Spruijt, Berry M; Ramakers, Geert M J

    2010-04-01

    Chronic stress causes insensitivity to rewards (anhedonia) in rats, reflected by the absence of anticipatory behavior for a sucrose-reward, which can be reversed by antidepressant treatment or repeated announced transfer to an enriched cage. It was, however, not clear whether the highly rewarding properties of the enriched cage alone caused this reversal or whether the anticipation of this reward as such had an additional effect. Therefore, the present study compared the consequences of the announcement of a reward to the mere effect of a reward alone with respect to their efficacy to counteract the consequences of chronic stress. Two forms of synaptic plasticity, long-term potentiation and long-term depression were investigated in area CA1 of the hippocampus. This was done in socially stressed rats (induced by defeat and subsequent long-term individual housing), socially stressed rats that received a reward (short-term enriched housing) and socially stressed rats to which this reward was announced by means of a stimulus that was repeatedly paired to the reward. The results were compared to corresponding control rats. We show that announcement of enriched housing appeared to have had an additional effect compared to the enriched housing per se as indicated by a significant higher amount of LTP. In conclusion, announced short-term enriched housing has a high and long-lasting counteracting efficacy on stress-induced alterations of hippocampal synaptic plasticity. This information is important for counteracting the consequences of chronic stress in both human and captive rats.

  17. AAV-mediated pancreatic overexpression of Igf1 counteracts progression to autoimmune diabetes in mice.

    Science.gov (United States)

    Mallol, Cristina; Casana, Estefania; Jimenez, Veronica; Casellas, Alba; Haurigot, Virginia; Jambrina, Claudia; Sacristan, Victor; Morró, Meritxell; Agudo, Judith; Vilà, Laia; Bosch, Fatima

    2017-07-01

    Type 1 diabetes is characterized by autoimmune destruction of β-cells leading to severe insulin deficiency. Although many improvements have been made in recent years, exogenous insulin therapy is still imperfect; new therapeutic approaches, focusing on preserving/expanding β-cell mass and/or blocking the autoimmune process that destroys islets, should be developed. The main objective of this work was to test in non-obese diabetic (NOD) mice, which spontaneously develop autoimmune diabetes, the effects of local expression of Insulin-like growth factor 1 (IGF1), a potent mitogenic and pro-survival factor for β-cells with immunomodulatory properties. Transgenic NOD mice overexpressing IGF1 specifically in β-cells (NOD-IGF1) were generated and phenotyped. In addition, miRT-containing, IGF1-encoding adeno-associated viruses (AAV) of serotype 8 (AAV8-IGF1-dmiRT) were produced and administered to 4- or 11-week-old non-transgenic NOD females through intraductal delivery. Several histological, immunological, and metabolic parameters were measured to monitor disease over a period of 28-30 weeks. In transgenic mice, local IGF1 expression led to long-term suppression of diabetes onset and robust protection of β-cell mass from the autoimmune insult. AAV-mediated pancreatic-specific overexpression of IGF1 in adult animals also dramatically reduced diabetes incidence, both when vectors were delivered before pathology onset or once insulitis was established. Transgenic NOD-IGF1 and AAV8-IGF1-dmiRT-treated NOD animals had much less islet infiltration than controls, preserved β-cell mass, and normal insulinemia. Transgenic and AAV-treated islets showed less expression of antigen-presenting molecules, inflammatory cytokines, and chemokines important for tissue-specific homing of effector T cells, suggesting IGF1 modulated islet autoimmunity in NOD mice. Local expression of Igf1 by AAV-mediated gene transfer counteracts progression to diabetes in NOD mice. This study suggests a

  18. Buspirone Counteracts MK-801-Induced Schizophrenia-Like Phenotypes through Dopamine D3 Receptor Blockade

    Science.gov (United States)

    Torrisi, Sebastiano Alfio; Salomone, Salvatore; Geraci, Federica; Caraci, Filippo; Bucolo, Claudio; Drago, Filippo; Leggio, Gian Marco

    2017-01-01

    Background: Several efforts have been made to develop effective antipsychotic drugs. Currently, available antipsychotics are effective on positive symptoms, less on negative symptoms, but not on cognitive impairment, a clinically relevant dimension of schizophrenia. Drug repurposing offers great advantages over the long-lasting, risky and expensive, de novo drug discovery strategy. To our knowledge, the possible antipsychotic properties of buspirone, an azapirone anxiolytic drug marketed in 1986 as serotonin 5-HT1A receptor (5-HT1AR) partial agonist, have not been extensively investigated despite its intriguing pharmacodynamic profile, which includes dopamine D3 (D3R) and D4 receptor (D4R) antagonist activity. Multiple lines of evidence point to D3R as a valid therapeutic target for the treatment of several neuropsychiatric disorders including schizophrenia. In the present study, we tested the hypothesis that buspirone, behaving as dopamine D3R antagonist, may have antipsychotic-like activity. Materials and Methods: Effects of acute administration of buspirone was assessed on a wide-range of schizophrenia-relevant abnormalities induced by a single administration of the non-competitive NMDAR antagonist MK-801, in both wild-type mice (WT) and D3R-null mutant mice (D3R-/-). Results: Buspirone (3 mg⋅kg-1, i.p.) was devoid of cataleptogenic activity in itself, but resulted effective in counteracting disruption of prepulse inhibition (PPI), hyperlocomotion and deficit of temporal order recognition memory (TOR) induced by MK-801 (0.1 mg⋅kg-1, i.p.) in WT mice. Conversely, in D3R-/- mice, buspirone was ineffective in preventing MK-801-induced TOR deficit and it was only partially effective in blocking MK-801-stimulated hyperlocomotion. Conclusion: Taken together, these results indicate, for the first time, that buspirone, might be a potential therapeutic medication for the treatment of schizophrenia. In particular, buspirone, through its D3R antagonist activity, may be

  19. Survivin counteracts the therapeutic effect of microtubule de-stabilizers by stabilizing tubulin polymers

    Directory of Open Access Journals (Sweden)

    Hsieh Hsing-Pang

    2009-07-01

    stability of microtubules, but not with caspases inhibition. Over-expression of survivin counteracts the therapeutic effect of microtubule de-stabilizer BPR0L075 probably by stabilizing tubulin polymers, instead of the inhibition of caspase activity in cancer cells. Besides microtubule-related caspase-dependent cell death, caspase-independent mitotic cell death could be initiated in survivin/BPR0L075 combination treatments. We suggest that combining microtubule de-stabilizers with a survivin inhibitor may attribute to a better clinical outcome than the use of anti-mitotic monotherapy in clinical situations.

  20. The Combination of Physical Exercise with Muscle-Directed Antioxidants to Counteract Sarcopenia: A Biomedical Rationale for Pleiotropic Treatment with Creatine and Coenzyme Q10

    Directory of Open Access Journals (Sweden)

    Michele Guescini

    2017-01-01

    Full Text Available Sarcopenia represents an increasing public health risk due to the rapid aging of the world’s population. It is characterized by both low muscle mass and function and is associated with mobility disorders, increased risk of falls and fractures, loss of independence, disabilities, and increased risk of death. Despite the urgency of the problem, the development of treatments for sarcopenia has lagged. Increased reactive oxygen species (ROS production and decreased antioxidant (AO defences seem to be important factors contributing to muscle impairment. Studies have been conducted to verify whether physical exercise and/or AOs could prevent and/or delay sarcopenia through a normalization of the etiologically relevant ROS imbalance. Despite the strong rationale, the results obtained were contradictory, particularly with regard to the effects of the tested AOs. A possible explanation might be that not all the agents included in the general heading of “AOs” could fulfill the requisites to counteract the complex series of events causing/accelerating sarcopenia: the combination of the muscle-directed antioxidants creatine and coenzyme Q10 with physical exercise as a biomedical rationale for pleiotropic prevention and/or treatment of sarcopenia is discussed.

  1. Vitamin D Counteracts Mycobacterium tuberculosis-Induced Cathelicidin Downregulation in Dendritic Cells and Allows Th1 Differentiation and IFNγ Secretion

    Directory of Open Access Journals (Sweden)

    Anna K. O. Rode

    2017-05-01

    Full Text Available Tuberculosis (TB presents a serious health problem with approximately one-third of the world’s population infected with Mycobacterium tuberculosis in a latent state. Experience from the pre-antibiotic era and more recent clinical studies have established a beneficial role of sunlight and vitamin D in patients with TB. At the same time, experimental data have shown that Th1 cells through production of IFNγ are crucial for cathelicidin release by macrophages, bacterial killing, and containment of M. tuberculosis in granulomas. Paradoxically, vitamin D has repeatedly been ascribed an immune-suppressive function inhibiting Th1 differentiation and production of IFNγ in T cells. The aim of this study was to investigate this apparent paradox. We studied naïve human CD4+ T cells activated either with CD3 and CD28 antibodies or with allogeneic dendritic cells (DC stimulated with heat-killed M. tuberculosis (HKMT or purified toll-like receptor (TLR ligands. We show that vitamin D does not block differentiation of human CD4+ T cells to Th1 cells and that interleukin (IL-12 partially counteracts vitamin D-mediated inhibition of IFNγ production promoting production of equal amounts of IFNγ in Th1 cells in the presence of vitamin D as in T cells activated in the absence of vitamin D and IL-12. Furthermore, we show that HKMT and TLR2 ligands strongly downregulate cathelicidin expression in DC and that vitamin D counteracts this by upregulating cathelicidin expression. In conclusion, we demonstrate that vitamin D counteracts M. tuberculosis-induced cathelicidin downregulation and allows Th1 differentiation and IFNγ secretion.

  2. Vitamin D Counteracts Mycobacterium tuberculosis-Induced Cathelicidin Downregulation in Dendritic Cells and Allows Th1 Differentiation and IFNγ Secretion.

    Science.gov (United States)

    Rode, Anna K O; Kongsbak, Martin; Hansen, Marie M; Lopez, Daniel Villalba; Levring, Trine B; Woetmann, Anders; Ødum, Niels; Bonefeld, Charlotte M; Geisler, Carsten

    2017-01-01

    Tuberculosis (TB) presents a serious health problem with approximately one-third of the world's population infected with Mycobacterium tuberculosis in a latent state. Experience from the pre-antibiotic era and more recent clinical studies have established a beneficial role of sunlight and vitamin D in patients with TB. At the same time, experimental data have shown that Th1 cells through production of IFNγ are crucial for cathelicidin release by macrophages, bacterial killing, and containment of M. tuberculosis in granulomas. Paradoxically, vitamin D has repeatedly been ascribed an immune-suppressive function inhibiting Th1 differentiation and production of IFNγ in T cells. The aim of this study was to investigate this apparent paradox. We studied naïve human CD4 + T cells activated either with CD3 and CD28 antibodies or with allogeneic dendritic cells (DC) stimulated with heat-killed M. tuberculosis (HKMT) or purified toll-like receptor (TLR) ligands. We show that vitamin D does not block differentiation of human CD4 + T cells to Th1 cells and that interleukin (IL)-12 partially counteracts vitamin D-mediated inhibition of IFNγ production promoting production of equal amounts of IFNγ in Th1 cells in the presence of vitamin D as in T cells activated in the absence of vitamin D and IL-12. Furthermore, we show that HKMT and TLR2 ligands strongly downregulate cathelicidin expression in DC and that vitamin D counteracts this by upregulating cathelicidin expression. In conclusion, we demonstrate that vitamin D counteracts M. tuberculosis -induced cathelicidin downregulation and allows Th1 differentiation and IFNγ secretion.

  3. NSs protein of Schmallenberg virus counteracts the antiviral response of the cell by inhibiting its transcriptional machinery.

    Science.gov (United States)

    Barry, Gerald; Varela, Mariana; Ratinier, Maxime; Blomström, Anne-Lie; Caporale, Marco; Seehusen, Frauke; Hahn, Kerstin; Schnettler, Esther; Baumgärtner, Wolfgang; Kohl, Alain; Palmarini, Massimo

    2014-08-01

    Bunyaviruses have evolved a variety of strategies to counteract the antiviral defence systems of mammalian cells. Here we show that the NSs protein of Schmallenberg virus (SBV) induces the degradation of the RPB1 subunit of RNA polymerase II and consequently inhibits global cellular protein synthesis and the antiviral response. In addition, we show that the SBV NSs protein enhances apoptosis in vitro and possibly in vivo, suggesting that this protein could be involved in SBV pathogenesis in different ways. © 2014 The Authors.

  4. A result on the acoustic characteristics of the Mixture of Counter-phase Counteract and Split-gas Rushing muffler

    Directory of Open Access Journals (Sweden)

    Shao Ying-li

    2016-01-01

    Full Text Available The exhaust noise, which falls into low-frequency noise, is the dominant noise source of a diesel engines and tractors. The traditional exhaust silencers, which are normally constructed by combination of expansion chamber, and perforated pipe or perforated board, are with high exhaust resistance, but poor noise reduction especially for the low-frequency band noise. For this reason, a new theory of exhaust muffler of diesel engine based on counter-phase counteracts has been proposed. The mathematical model and the corresponding experimental validation for the new exhaust muffler based on this theory were performed.

  5. Flavanol-rich chocolate acutely improves arterial function and working memory performance counteracting the effects of sleep deprivation in healthy individuals.

    Science.gov (United States)

    Grassi, Davide; Socci, Valentina; Tempesta, Daniela; Ferri, Claudio; De Gennaro, Luigi; Desideri, Giovambattista; Ferrara, Michele

    2016-07-01

    Sleep deprivation is a risk factor for cardiovascular disease. Cocoa flavonoids exert cardiovascular benefits and neuroprotection. Whether chocolate consumption may mitigate detrimental effects of sleep loss on cognitive performance and cardiovascular parameters has never been studied. We investigated the effects of flavanol-rich chocolate consumption on cognitive skills and cardiovascular parameters after sleep deprivation. Thirty-two healthy participants underwent two baseline sessions after one night of undisturbed sleep and two experimental sessions after one night of total sleep deprivation. Two hours before each testing session, participants were randomly assigned to consume high or poor flavanol chocolate bars. During the tests were evaluated, the Psychomotor Vigilance Task and a working memory task, office SBP and DBP, flow-mediated dilation and pulse-wave velocity. Sleep deprivation increased SBP/DBP. SBP/DBP and pulse pressure were lower after flavanol-rich treatment respect to flavanol-poor treatment (SBP: 116.9 ± 1.6 vs. 120.8 ± 1.9 mmHg, respectively, P = 0.00005; DBP: 70.5 ± 1.2 vs. 72.3 ± 1.2 mmHg, respectively, P = 0.01; pulse pressure: 46.4 ± 1.3 vs. 48.4 ± 1.5 mmHg, P = 0.004). Sleep deprivation impaired flow-mediated dilation (5.5 ± 0.5 vs. 6.5 ± 0.6%, P = 0.02), flavanol-rich, but not flavanol-poor chocolate counteracted this alteration (flavanol-rich/flavanol-poor chocolate: 7.0 ± 0.6 vs. 5.0 ± 0.4%, P = 0.000001). Flavanol-rich chocolate mitigated the pulse-wave velocity increase (P = 0.001). Flavanol-rich chocolate preserved working memory accuracy in women after sleep deprivation. Flow-mediated dilation correlated with working memory performance accuracy in the sleep condition (P = 0.04). Flavanol-rich chocolate counteracted vascular impairment after sleep deprivation and restored working memory performance. Improvement in cognitive performance could be because

  6. Simultaneous ultrasound-assisted water extraction and β-cyclodextrin encapsulation of polyphenols from Mangifera indica stem bark in counteracting TNFα-induced endothelial dysfunction.

    Science.gov (United States)

    Mura, Marzia; Palmieri, Daniela; Garella, Davide; Di Stilo, Antonella; Perego, Patrizia; Cravotto, Giancarlo; Palombo, Domenico

    2015-01-01

    This study proposes an alternative technique to prevent heat degradation induced by classic procedures of bioactive compound extraction, comparing classical maceration/decoction in hot water of polyphenols from Mango (Mangifera indica L.) (MI) with ultrasound-assisted extraction (UAE) in a water solution of β-cyclodextrin (β-CD) at room temperature and testing their biological activity on TNFα-induced endothelial dysfunction. Both extracts counteracted TNFα effects on EAhy926 cells, down-modulating interleukin-6, interleukin-8, cyclooxygenase-2 and intracellular adhesion molecule-1, while increasing endothelial nitric oxide synthase levels. β-CD extract showed higher efficacy in improving endothelial function. These effects were abolished after pre-treatment with the oestrogen receptor inhibitor ICI1182,780. Moreover, the β-CD extract induced Akt activation and completely abolished the TNFα-induced p38MAPK phosphorylation. UAE and β-CD encapsulation provide an efficient extraction protocol that increases polyphenol bioavailability. Polyphenols from MI play a protective role on endothelial cells and may be further considered as oestrogen-like molecules with vascular protective properties.

  7. Smoking Counteracts the Favorable Effect of Exercise Training on Endothelial Function in Patients with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Shinji Sato

    2013-01-01

    Full Text Available Background Exercise training can improve endothelial function in patients with diabetes. We hypothesized that the favorable effect of exercise training on endothelial function in patients with diabetes is counteracted by cigarette smoking. Purpose To assess whether there is a difference in the effect of exercise on endothelial function in smokers and non-smokers with type 2 diabetes. Methods We performed a 3-month controlled trial in 27 never-smoking and 17 smoking individuals with type 2 diabetes who participated in a home-based walking program. The percentage decrease in post-exercise ankle-brachial pressure index (ABI, which is an index of endothelial function, was assessed at baseline and after 3 months. Results Compared to the smoking group, the never-smoking group showed a more significant improvement in post exercise ABI during the 3 months of home-based training (interaction, P < 0.01. Conclusions These results indicate that smoking may counteract the favorable effects of exercise training on endothelial function. Endothelial function plays an important role in the prevention of cardiovascular disease among patients with diabetes. Therefore, a Certified Diabetes Educator should strongly advise diabetic patients not to smoke.

  8. Counteraction of urea-induced protein denaturation by trimethylamine N-oxide: a chemical chaperone at atomic resolution.

    Science.gov (United States)

    Bennion, Brian J; Daggett, Valerie

    2004-04-27

    Proteins are very sensitive to their solvent environments. Urea is a common chemical denaturant of proteins, yet some animals contain high concentrations of urea. These animals have evolved an interesting mechanism to counteract the effects of urea by using trimethylamine N-oxide (TMAO). The molecular basis for the ability of TMAO to act as a chemical chaperone remains unknown. Here, we describe molecular dynamics simulations of a small globular protein, chymotrypsin inhibitor 2, in 8 M urea and 4 M TMAO/8 M urea solutions, in addition to other control simulations, to investigate this effect at the atomic level. In 8 M urea, the protein unfolds, and urea acts in both a direct and indirect manner to achieve this effect. In contrast, introduction of 4 M TMAO counteracts the effect of urea and the protein remains well structured. TMAO makes few direct interactions with the protein. Instead, it prevents unfolding of the protein by structuring the solvent. In particular, TMAO orders the solvent and discourages it from competing with intraprotein H bonds and breaking up the hydrophobic core of the protein.

  9. Arabidopsis Glutamate Receptor Homolog3.5 Modulates Cytosolic Ca2+ Level to Counteract Effect of Abscisic Acid in Seed Germination1[OPEN

    Science.gov (United States)

    Kong, Dongdong; Ju, Chuanli; Parihar, Aisha; Kim, So; Cho, Daeshik; Kwak, June M.

    2015-01-01

    Seed germination is a critical step in a plant’s life cycle that allows successful propagation and is therefore strictly controlled by endogenous and environmental signals. However, the molecular mechanisms underlying germination control remain elusive. Here, we report that the Arabidopsis (Arabidopsis thaliana) glutamate receptor homolog3.5 (AtGLR3.5) is predominantly expressed in germinating seeds and increases cytosolic Ca2+ concentration that counteracts the effect of abscisic acid (ABA) to promote germination. Repression of AtGLR3.5 impairs cytosolic Ca2+ concentration elevation, significantly delays germination, and enhances ABA sensitivity in seeds, whereas overexpression of AtGLR3.5 results in earlier germination and reduced seed sensitivity to ABA. Furthermore, we show that Ca2+ suppresses the expression of ABSCISIC ACID INSENSITIVE4 (ABI4), a key transcription factor involved in ABA response in seeds, and that ABI4 plays a fundamental role in modulation of Ca2+-dependent germination. Taken together, our results provide molecular genetic evidence that AtGLR3.5-mediated Ca2+ influx stimulates seed germination by antagonizing the inhibitory effects of ABA through suppression of ABI4. These findings establish, to our knowledge, a new and pivotal role of the plant glutamate receptor homolog and Ca2+ signaling in germination control and uncover the orchestrated modulation of the AtGLR3.5-mediated Ca2+ signal and ABA signaling via ABI4 to fine-tune the crucial developmental process, germination, in Arabidopsis. PMID:25681329

  10. A Pilot Examination of the Methods Used to Counteract Insider Threat Security Risks Associated with the Use of Radioactive Materials in the Research and Clinical Setting.

    Science.gov (United States)

    Tsenov, B G; Emery, R J; Whitehead, L W; Gonzalez, J Reingle; Gemeinhardt, G L

    2018-03-01

    While many organizations maintain multiple layers of security control methodologies to prevent outsiders from gaining unauthorized access, persons such as employees or contractors who have been granted legitimate access can represent an "insider threat" risk. Interestingly, some of the most notable radiological events involving the purposeful contamination or exposure of individuals appear to have been perpetrated by insiders. In the academic and medical settings, radiation safety professionals focus their security efforts on (1) ensuring controls are in place to prevent unauthorized access or removal of sources, and (2) increasing security controls for the unescorted accessing of large sources of radioactivity (known as "quantities of concern"). But these controls may not completely address the threat insiders represent when radioactive materials below these quantities are present. The goal of this research project was to characterize the methodologies currently employed to counteract the insider security threat for the misuse or purposeful divergence of radioactive materials used in the academic and medical settings. A web-based survey was used to assess how practicing radiation safety professionals in academic and medical settings anticipate, evaluate, and control insider threat security risks within their institutions. While all respondents indicated that radioactive sources are being used in amounts below quantities of concern, only 6 % consider insider threat security issues as part of the protocol review for the use of general radioactive materials. The results of this survey identify several opportunities for improvement for institutions to address security gaps.

  11. Dopamine D4 Receptor Counteracts Morphine-Induced Changes in µ Opioid Receptor Signaling in the Striosomes of the Rat Caudate Putamen

    Directory of Open Access Journals (Sweden)

    Diana Suárez-Boomgaard

    2014-01-01

    Full Text Available The mu opioid receptor (MOR is critical in mediating morphine analgesia. However, prolonged exposure to morphine induces adaptive changes in this receptor leading to the development of tolerance and addiction. In the present work we have studied whether the continuous administration of morphine induces changes in MOR protein levels, its pharmacological profile, and MOR-mediated G-protein activation in the striosomal compartment of the rat CPu, by using immunohistochemistry and receptor and DAMGO-stimulated [35S]GTPγS autoradiography. MOR immunoreactivity, agonist binding density and its coupling to G proteins are up-regulated in the striosomes by continuous morphine treatment in the absence of changes in enkephalin and dynorphin mRNA levels. In addition, co-treatment of morphine with the dopamine D4 receptor (D4R agonist PD168,077 fully counteracts these adaptive changes in MOR, in spite of the fact that continuous PD168,077 treatment increases the [3H]DAMGO Bmax values to the same degree as seen after continuous morphine treatment. Thus, in spite of the fact that both receptors can be coupled to Gi/0 protein, the present results give support for the existence of antagonistic functional D4R-MOR receptor-receptor interactions in the adaptive changes occurring in MOR of striosomes on continuous administration of morphine.

  12. Forms of the criminal environment counteraction to performing the function of state protection of participants in criminal proceedings and measures of its neutralization

    Directory of Open Access Journals (Sweden)

    Dubonosov E.S.

    2014-12-01

    Full Text Available Criminal environment’s counteraction is considered as purposeful, active and intentional influence of its representatives on participants in criminal proceedings. It is directed at persons who, due to their professional duties, are involved in detection and investigation of crimes as well as court proceedings, or who possess evidentiary information (witnesses, victims, etc.. Counteraction may be expressed in different ways: discrediting operatives, investigators and judges; pressure on persons involved in the investigation and the trial through bribery, blackmail, threats to life and health of themselves and their family, etc. The administration of justice becomes inefficient due to the variety of forms and purposes of counteraction. The importance of operational units’ awareness of the activities of criminal environment representatives is shown. The importance of revealing the facts of unlawful influence on witnesses and victims of crime, who subsequently acquire procedural status of witnesses and victims, in order to prevent such facts is also stressed. It is proposed to suppress the counteraction of criminal environment by following ways: 1 identifying (with the help of informants and by crime detection actions the persons attempting to influence the preliminary investigation; 2 documenting the suspects actions aimed at illegal influence on participants in criminal proceedings for the purpose of conducting the procedural actions and decision making; 3 “in cell” (using an agent crime detection actions against detainees and arrestees throughout the whole process of covert operation; 4 creating investigative team to develop a common mechanism to neutralize criminal environment’s counteraction to crime investigation.

  13. Excessive islet NO generation in type 2 diabetic GK rats coincides with abnormal hormone secretion and is counteracted by GLP-1.

    Directory of Open Access Journals (Sweden)

    Albert Salehi

    Full Text Available BACKGROUND: A distinctive feature of type 2 diabetes is inability of insulin-secreting beta-cells to properly respond to elevated glucose eventually leading to beta-cell failure. We have hypothesized that an abnormally increased NO production in the pancreatic islets might be an important factor in the pathogenesis of beta-cell dysfunction. PRINCIPAL FINDINGS: We show now that islets of type 2 spontaneous diabetes in GK rats display excessive NO generation associated with abnormal iNOS expression in insulin and glucagon cells, increased ncNOS activity, impaired glucose-stimulated insulin release, glucagon hypersecretion, and impaired glucose-induced glucagon suppression. Pharmacological blockade of islet NO production by the NOS inhibitor N(G-nitro-L-arginine methyl ester (L-NAME greatly improved hormone secretion from GK islets suggesting islet NOS activity being an important target to inactivate for amelioration of islet cell function. The incretin hormone GLP-1, which is used in clinical practice suppressed iNOS and ncNOS expression and activity with almost full restoration of insulin release and partial restoration of glucagon release. GLP-1 suppression of iNOS expression was reversed by PKA inhibition but unaffected by the proteasome inhibitor MG132. Injection of glucose plus GLP-1 in the diabetic rats showed that GLP-1 amplified the insulin response but induced a transient increase and then a poor depression of glucagon. CONCLUSION: The results suggest that abnormally increased NO production within islet cells is a significant player in the pathogenesis of type 2 diabetes being counteracted by GLP-1 through PKA-dependent, nonproteasomal mechanisms.

  14. Vitamin D counteracts Mycobacterium tuberculosis-induced cathelicidin downregulation in dendritic cells and allows Th1 differentiation and IFNγ secretion

    DEFF Research Database (Denmark)

    Rode, Anna K.O.; Kongsbak, Martin; Hansen, Marie M.

    2017-01-01

    -suppressive function inhibiting Th1 differentiation and production of IFNγ in T cells. The aim of this study was to investigate this apparent paradox. We studied naïve human CD4+ T cells activated either with CD3 and CD28 antibodies or with allogeneic dendritic cells (DC) stimulated with heat-killed M. tuberculosis...... (HKMT) or purified toll-like receptor (TLR) ligands. We show that vitamin D does not block differentiation of human CD4+ T cells to Th1 cells and that interleukin (IL)-12 partially counteracts vitamin D-mediated inhibition of IFNγ production promoting production of equal amounts of IFNγ in Th1 cells...... in patients with TB. At the same time, experimental data have shown that Th1 cells through production of IFNγ are crucial for cathelicidin release by macrophages, bacterial killing, and containment of M. tuberculosis in granulomas. Paradoxically, vitamin D has repeatedly been ascribed an immune...

  15. Haloperidol counteracts the ketamine-induced disruption of processing negativity, but not that of the P300 amplitude

    DEFF Research Database (Denmark)

    Oranje, Bob; Gispen-de Wied, Christine C; Westenberg, Herman G M

    2009-01-01

    . Besides exerting an antagonistic effect on NMDA receptors, they have agonistic effects on dopamine D2 receptors. Can haloperidol (D2 antagonist) counteract the disruptive effects of ketamine on psychophysiological parameters of human attention? In a randomized, double-blind, placebo-controlled experiment...... 18 healthy male volunteers received placebo/placebo, placebo/ketamine (0.3 mg/kg i.v.) and haloperidol (2 mg)/ketamine (0.3 mg/kg i.v.) on three separate test days, after which they were tested in an auditory selective-attention paradigm. Haloperidol/ketamine reduced task performance compared...... to placebo/placebo, while the task performance in these two treatments did not differ from placebo/ketamine. Furthermore, placebo/ketamine reduced processing negativity compared to both placebo/placebo and haloperidol/ketamine, while processing negativity did not differ between placebo...

  16. Grazing management can counteract the impacts of climate change-induced sea level rise on salt marsh-dependent waterbirds

    DEFF Research Database (Denmark)

    Clausen, Kevin Kuhlmann; Stjernholm, Michael; Clausen, Preben

    2013-01-01

    with these changes. In addition, we quantify the areal extent of inadequate salt marsh management in four EU Special Protection Areas for Birds, and demonstrate concurrent population dynamics in four species relying on managed habitats. We conclude by investigating potential compensation for climate change......1) Climate change–induced rises in sea level threaten to drastically reduce the areal extent of important salt marsh habitats for large numbers of waterfowl and waders. Furthermore, recent changes in management practice have rendered existent salt marshes unfavourable to many birds, as lack...... (around 1 cow per hectare) is an important initiative to counteract the accelerating climate change–induced habitat loss in near-coastal areas across the globe, and to secure priority salt marsh habitats that support internationally important populations of breeding, wintering and staging waterfowl...

  17. Phenylbutyrate counteracts Shigella mediated downregulation of cathelicidin in rabbit lung and intestinal epithelia: a potential therapeutic strategy.

    Directory of Open Access Journals (Sweden)

    Protim Sarker

    Full Text Available BACKGROUND: Cathelicidins and defensins are endogenous antimicrobial peptides (AMPs that are downregulated in the mucosal epithelia of the large intestine in shigellosis. Oral treatment of Shigella infected rabbits with sodium butyrate (NaB reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18 in the large intestinal epithelia. AIMS: To develop novel regimen for treating infectious diseases by inducing innate immunity, we selected sodium 4-phenylbutyrate (PB, a registered drug for a metabolic disorder as a potential therapeutic candidate in a rabbit model of shigellosis. Since acute respiratory infections often cause secondary complications during shigellosis, the systemic effect of PB and NaB on CAP-18 expression in respiratory epithelia was also evaluated. METHODS: The readouts were clinical outcomes, CAP-18 expression in mucosa of colon, rectum, lung and trachea (immunohistochemistry and real-time PCR and release of the CAP-18 peptide/protein in stool (Western blot. PRINCIPAL FINDINGS: Significant downregulation of CAP-18 expression in the epithelia of rectum and colon, the site of Shigella infection was confirmed. Interestingly, reduced expression of CAP-18 was also noticed in the epithelia of lung and trachea, indicating a systemic effect of the infection. This suggests a causative link to acute respiratory infections during shigellosis. Oral treatment with PB resulted in reduced clinical illness and upregulation of CAP-18 in the epithelium of rectum. Both PB and NaB counteracted the downregulation of CAP-18 in lung epithelium. The drug effect is suggested to be systemic as intravenous administration of NaB could also upregulate CAP-18 in the epithelia of lung, rectum and colon. CONCLUSION: Our results suggest that PB has treatment potential in human shigellosis. Enhancement of CAP-18 in the mucosal epithelia of the respiratory tract by PB or NaB is a novel discovery. This could mediate protection from

  18. Phenylbutyrate counteracts Shigella mediated downregulation of cathelicidin in rabbit lung and intestinal epithelia: a potential therapeutic strategy.

    Science.gov (United States)

    Sarker, Protim; Ahmed, Sultan; Tiash, Snigdha; Rekha, Rokeya Sultana; Stromberg, Roger; Andersson, Jan; Bergman, Peter; Gudmundsson, Gudmundur H; Agerberth, Birgitta; Raqib, Rubhana

    2011-01-01

    Cathelicidins and defensins are endogenous antimicrobial peptides (AMPs) that are downregulated in the mucosal epithelia of the large intestine in shigellosis. Oral treatment of Shigella infected rabbits with sodium butyrate (NaB) reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18) in the large intestinal epithelia. To develop novel regimen for treating infectious diseases by inducing innate immunity, we selected sodium 4-phenylbutyrate (PB), a registered drug for a metabolic disorder as a potential therapeutic candidate in a rabbit model of shigellosis. Since acute respiratory infections often cause secondary complications during shigellosis, the systemic effect of PB and NaB on CAP-18 expression in respiratory epithelia was also evaluated. The readouts were clinical outcomes, CAP-18 expression in mucosa of colon, rectum, lung and trachea (immunohistochemistry and real-time PCR) and release of the CAP-18 peptide/protein in stool (Western blot). Significant downregulation of CAP-18 expression in the epithelia of rectum and colon, the site of Shigella infection was confirmed. Interestingly, reduced expression of CAP-18 was also noticed in the epithelia of lung and trachea, indicating a systemic effect of the infection. This suggests a causative link to acute respiratory infections during shigellosis. Oral treatment with PB resulted in reduced clinical illness and upregulation of CAP-18 in the epithelium of rectum. Both PB and NaB counteracted the downregulation of CAP-18 in lung epithelium. The drug effect is suggested to be systemic as intravenous administration of NaB could also upregulate CAP-18 in the epithelia of lung, rectum and colon. Our results suggest that PB has treatment potential in human shigellosis. Enhancement of CAP-18 in the mucosal epithelia of the respiratory tract by PB or NaB is a novel discovery. This could mediate protection from secondary respiratory infections that frequently are the lethal causes in

  19. Albedo enhancement of marine clouds to counteract global warming: impacts on the hydrological cycle

    Energy Technology Data Exchange (ETDEWEB)

    Bala, G. [Indian Institute of Science, Divecha Center for Climate Change, Bangalore (India); Indian Institute of Science, Center for Atmospheric and Oceanic Sciences, Bangalore (India); Caldeira, Ken; Cao, Long; Ban-Weiss, George; Shin, Ho-Jeong [Carnegie Institution, Department of Global Ecology, Stanford, CA (United States); Nemani, Rama [NASA Ames Research Center, Moffett Field, CA (United States)

    2011-09-15

    Recent studies have shown that changes in solar radiation affect the hydrological cycle more strongly than equivalent CO{sub 2} changes for the same change in global mean surface temperature. Thus, solar radiation management ''geoengineering'' proposals to completely offset global mean temperature increases by reducing the amount of absorbed sunlight might be expected to slow the global water cycle and reduce runoff over land. However, proposed countering of global warming by increasing the albedo of marine clouds would reduce surface solar radiation only over the oceans. Here, for an idealized scenario, we analyze the response of temperature and the hydrological cycle to increased reflection by clouds over the ocean using an atmospheric general circulation model coupled to a mixed layer ocean model. When cloud droplets are reduced in size over all oceans uniformly to offset the temperature increase from a doubling of atmospheric CO{sub 2}, the global-mean precipitation and evaporation decreases by about 1.3% but runoff over land increases by 7.5% primarily due to increases over tropical land. In the model, more reflective marine clouds cool the atmospheric column over ocean. The result is a sinking motion over oceans and upward motion over land. We attribute the increased runoff over land to this increased upward motion over land when marine clouds are made more reflective. Our results suggest that, in contrast to other proposals to increase planetary albedo, offsetting mean global warming by reducing marine cloud droplet size does not necessarily lead to a drying, on average, of the continents. However, we note that the changes in precipitation, evaporation and P-E are dominated by small but significant areas, and given the highly idealized nature of this study, a more thorough and broader assessment would be required for proposals of altering marine cloud properties on a large scale. (orig.)

  20. Peatland plant communities under global change: negative feedback loops counteract shifts in species composition.

    Science.gov (United States)

    Hedwall, Per-Ola; Brunet, Jörg; Rydin, Håkan

    2017-01-01

    Mires (bogs and fens) are nutrient-limited peatland ecosystems, the vegetation of which is especially sensitive to nitrogen deposition and climate change. The role of mires in the global carbon cycle, and the delivery of different ecosystem services can be considerably altered by changes in the vegetation, which has a strong impact on peat-formation and hydrology. Mire ecosystems are commonly open with limited canopy cover but both nitrogen deposition and increased temperatures may increase the woody vegetation component. It has been predicted that such an increase in tree cover and the associated effects on light and water regimes would cause a positive feed-back loop with respect to the ground vegetation. None of these effects, however, have so far been confirmed in large-scale spatiotemporal studies. Here we analyzed data pertaining to mire vegetation from the Swedish National Forest Inventory collected from permanent sample plots over a period of 20 yr along a latitudinal gradient covering 14°. We hypothesized that the changes would be larger in the southern parts as a result of higher nitrogen deposition and warmer climate. Our results showed an increase in woody vegetation with increases in most ericaceous dwarf-shrubs and in the basal area of trees. These changes were, in contrast to our expectations, evenly distributed over most of the latitudinal gradient. While nitrogen deposition is elevated in the south, the increase in temperatures during recent decades has been larger in the north. Hence, we suggest that different processes in the north and south have produced similar vegetation changes along the latitudinal gradient. There was, however, a sharp increase in compositional change at high deposition, indicating a threshold effect in the response. Instead of a positive feed-back loop caused by the tree layer, an increase in canopy cover reduced the changes in composition of the ground vegetation, whereas a decrease in canopy cover lead to larger changes

  1. The Nutraceutic Silybin Counteracts Excess Lipid Accumulation and Ongoing Oxidative Stress in an In Vitro Model of Non-Alcoholic Fatty Liver Disease Progression

    Directory of Open Access Journals (Sweden)

    Giulia Vecchione

    2017-09-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is a major cause of liver-related morbidity and mortality. Oxidative stress and release of pro-inflammatory cytokines, such as tumor necrosis factor α (TNFα, are major consequences of hepatic lipid overload, which can contribute to progression of NAFLD to non-alcoholic steatohepatitis (NASH. Also, mitochondria are involved in the NAFLD pathogenesis for their role in hepatic lipid metabolism. Definitive treatments for NAFLD/NASH are lacking so far. Silybin, the extract of the milk thistle seeds, has previously shown beneficial effects in NAFLD. Sequential exposure of hepatocytes to high concentrations of fatty acids (FAs and TNFα resulted in fat overload and oxidative stress, which mimic in vitro the progression of NAFLD from simple steatosis (SS to steatohepatitis (SH. The exposure to 50 µM silybin for 24 h reduced fat accumulation in the model of NAFLD progression. The in vitro progression of NAFLD from SS to SH resulted in reduced hepatocyte viability, increased apoptosis and oxidative stress, reduction in lipid droplet size, and up-regulation of IκB kinase β-interacting protein and adipose triglyceride lipase expressions. The direct action of silybin on SS or SH cells and the underlying mechanisms were assessed. Beneficial action of silybin was sustained by changes in expression/activity of peroxisome proliferator-activated receptors and enzymes for FA oxidation. Moreover, silybin counteracted the FA-induced mitochondrial damage by acting on complementary pathways: (i increased the mitochondrial size and improved the mitochondrial cristae organization; (ii stimulated mitochondrial FA oxidation; (iii reduced basal and maximal respiration and ATP production in SH cells; (iv stimulated ATP production in SS cells; and (v rescued the FA-induced apoptotic signals and oxidative stress in SH cells. We provide new insights about the direct protective effects of the nutraceutic silybin on hepatocytes

  2. 'Healthy children in sound communities' (HCSC/gkgk)--a Dutch-German community-based network project to counteract obesity and physical inactivity.

    Science.gov (United States)

    Naul, Roland; Schmelt, Dorothee; Dreiskaemper, Dennis; Hoffmann, Dirk; l'Hoir, Monique

    2012-04-01

    In 12 municipalities at the German-Dutch border an integrated approach of a multi-component intervention programme (physical activity, nutrition, public health, improvement of the physical environment) to enhance an active lifestyle has been implemented in 39 primary schools for a 4-year longitudinal intervention and evaluation study. A weekly lesson plan, including 3 hours of health enhanced physical education and two additional hours of physical activities offered by sport clubs to balance motor deficits and to reduce overweight and obesity was implemented. Furthermore, another hour of cross-curricular education of health and nutrition education is part of the school curriculum. To achieve 60 to 90 minutes of daily physical activities for 6- to 10-year-old pupils active commuting to school has become a part of school life. A physical fitness and motor development test is applied each school year including BMI measurements as a part of a socio-ecological concept. Intrapersonal developments of the pupils are measured by different questionnaires focusing on the individual social context of physical activity, nutrition habits and time allocation for electronic media. Original values of Motor Ability tests show significant increase in endurance, coordination, velocity and force tasks. Also first changes for BMI distribution are explored in only one year intervention. First results indicate the possibility to counteract obesity and to increase levels of physical fitness and motor development by a multi-component progamme and a multi-sector approach of intervention. The longitudinal design of the study allows having a look on long-term effects.

  3. Growth of antarctic cyanobacteria under ultraviolet radiation: UVA counteracts UVB inhibition

    International Nuclear Information System (INIS)

    Quesada, A.; Mouget, J.L.; Vincent, W.F.

    1995-01-01

    A mat-forming cyanobacterium (Phormidium murayi West and West) isolated from an ice-shelf pond in Antarctica was grown under white light combined with a range of UVA and UVB irradiance. The 4-day growth rate decreased under increasing ultraviolet (UV) radiation, with a ninefold greater response to UVB relative to UVA. In vivo absorbance spectra showed that UVA and to a greater extent UVB caused a decrease in phycocyanin/chlorophyll a and an increase in carotenoids/chlorophyll a. The phycocyanin/chlorophyll a ratio was closely and positively correlated to the UVB-inhibited growth rate. Under fixed spectral gradients of UV radiation, the growth inhibition effect was dominated by UVB. However, at specific UVB irradiances the inhibition of growth depended on the ratio of UVB to UVA, and growth rates increased linearly with increasing UVA. These results are consistent with the view that UVB inhibition represents the balance between damage and repair processes that are each controlled by separate wavebands. They also underscore the need to consider UV spectral balance in laboratory and field assays of UVB toxicity. 49 refs., 6 figs

  4. Counteracting fatigue in multiple sclerosis with right parietal anodal transcranial direct current stimulation

    NARCIS (Netherlands)

    Hanken, K.; Bosse, M.; Möhrke, K.; Eling, P.A.T.M.; Kastrup, A.; Antal, A.; Hildebrandt, H.

    2016-01-01

    Background: Fatigue in multiple sclerosis (MS) patients appears to correlate with vigilance decrement as reflected in an increase in reaction time and errors with prolonged time-on-task. Objectives: The aim of this study was to investigate whether anodal transcranial direct current stimulation

  5. Selenium-induced toxicity is counteracted by sulfur in broccoli (Brassica oleracea L. var. italic)

    Science.gov (United States)

    Selenium (Se) is an essential micronutrient for humans. Increasing Se content in food crops offers an effective approach to enhance the consumption of Se in human diets. A thoroughly understanding of the effects of Se on plant growth is important for Se biofortification in food crops. Given that Se ...

  6. Alpha-Lipoic acid counteracts the promoted oxidative DNA damage in the liver of septic rats

    International Nuclear Information System (INIS)

    Abd-Allah, Adel R.A.

    2006-01-01

    Viral, parasitic infections and chemical carcinogens are among the etiological factors of liver cancer. It seems important to study the initiating and promoting agents to evaluate the etiology and prevention of such life threatening disease. Intestine-derived bacteria product, lipopolysaccharide (LPS), is mainly detoxified by the liver. It has shown to induce a state of oxidative DNA damage is not fully investigated. Increased oxidative DNA damage and rate of cell proliferation may initiate or even promote cancer. In the present work, the capability of LPS to induce 8-hydroxydeoxyguanosine (8-HDG), a specific DNA adduct for oxidative DNA damage, in rat livers is tested. Furthermore, a possible protective effect of alpha lipoic acid (ALA) is also assessed. Investigated parameters are liver contents of glutathione (GSH), lipid peroxides (MDA), nitric oxide (NO) and 8-HDG in the liver-extracted DNA. Serum activities of ALT, AST and GGT as liver-function markers as well as IL2 are assessed. Moreover, liver histology is examined. LPS was given doses of 1, 3, 5, 7 and 9 mg/kg once i.p. while, the rat mortality was examined 24 hours later. ALA was given in doses of 50, 100 and 200 mg/kg once i.p. 3h before LPS is found to be 5mg/kg. LPS increased the level of 8-HDG, MDA and NO in the liver. It also induced acute liver necrosis and inflammatory cell infiltration as shown in liver-histopathology and in the significant increase in the activities of ALT, AST and GGT. LPS increased the serum level of IL2 as well. The dose 200mg/kg of ALA revealed a 100% protection against LPS-induced lethality. It also, prevented the LPS-induced increase in 8-HDG in liver extracted DNA, the liver contents of MDA and NO. ALA also rescued the LPS-induced GSH depletion. It corrected the liver function as shown by the prevention of increases in the activity of ALT, AST and GGT with a remarkable improvement in the liver histology. Moreover, it prevented the increase in serum level of IL2. These

  7. Cigarette smoke extract counteracts atheroprotective effects of high laminar flow on endothelial function

    Directory of Open Access Journals (Sweden)

    Sindy Giebe

    2017-08-01

    Full Text Available Tobacco smoking and hemodynamic forces are key stimuli in the development of endothelial dysfunction and atherosclerosis. High laminar flow has an atheroprotective effect on the endothelium and leads to a reduced response of endothelial cells to cardiovascular risk factors compared to regions with disturbed or low laminar flow. We hypothesize that the atheroprotective effect of high laminar flow could delay the development of endothelial dysfunction caused by cigarette smoking. Primary human endothelial cells were stimulated with increasing dosages of aqueous cigarette smoke extract (CSEaq. CSEaq reduced cell viability in a dose-dependent manner. The main mediator of cellular adaption to oxidative stress, nuclear factor erythroid 2-related factor 2 (NRF2 and its target genes heme oxygenase (decycling 1 (HMOX1 or NAD(PH quinone dehydrogenase 1 (NQO1 were strongly increased by CSEaq in a dose-dependent manner. High laminar flow induced elongation of endothelial cells in the direction of flow, activated the AKT/eNOS pathway, increased eNOS expression, phosphorylation and NO release. These increases were inhibited by CSEaq. Pro-inflammatory adhesion molecules intercellular adhesion molecule-1 (ICAM1, vascular cell adhesion molecule-1 (VCAM1, selectin E (SELE and chemokine (C-C motif ligand 2 (CCL2/MCP-1 were increased by CSEaq. Low laminar flow induced VCAM1 and SELE compared to high laminar flow. High laminar flow improved endothelial wound healing. This protective effect was inhibited by CSEaq in a dose-dependent manner through the AKT/eNOS pathway. Low as well as high laminar flow decreased adhesion of monocytes to endothelial cells. Whereas, monocyte adhesion was increased by CSEaq under low laminar flow, this was not evident under high laminar flow.This study shows the activation of major atherosclerotic key parameters by CSEaq. Within this process, high laminar flow is likely to reduce the harmful effects of CSEaq to a certain degree. The

  8. An Innovative Way of Utilizing Wave Energy to Counteract Eutrophication and Hypoxia

    DEFF Research Database (Denmark)

    Margheritini, Lucia; Claeson, Lennart

    2011-01-01

    One of the most urgent environmental issues in 415 coastal systems worldwide is eutrophication and hypoxia. Cause of eutrophication is the rapid increase in intensive agricultural practices, industrial activities, and population growth which together have increased nitrogen and phosphorus flows...... in the environment. This is a major problem in the Baltic Sea. The present study introduces the Wave-Energized Baltic Aeration Pump (WEBAP). This is one floating overtopping device that uses the collected overtopping water to oxygenate the sea bottom in areas suffering from eutrophication. This is done by using...... the driving head of the overtopping water temporarily stored in the reservoir flowing out through a long vertical pipe leading close to the bottom of the sea. The necessary amounts of oxygen and corresponding overtopping volumes in order to have a positive impact in a damaged environment have been considered...

  9. Prescription drug samples--does this marketing strategy counteract policies for quality use of medicines?

    Science.gov (United States)

    Groves, K E M; Sketris, I; Tett, S E

    2003-08-01

    Prescription drug samples, as used by the pharmaceutical industry to market their products, are of current interest because of their influence on prescribing, and their potential impact on consumer safety. Very little research has been conducted into the use and misuse of prescription drug samples, and the influence of samples on health policies designed to improve the rational use of medicines. This is a topical issue in the prescription drug debate, with increasing costs and increasing concerns about optimizing use of medicines. This manuscript critically evaluates the research that has been conducted to date about prescription drug samples, discusses the issues raised in the context of traditional marketing theory, and suggests possible alternatives for the future.

  10. Albedo enhancement over land to counteract global warming: impacts on hydrological cycle

    Energy Technology Data Exchange (ETDEWEB)

    Bala, Govindasamy; Nag, Bappaditya [Indian Institute of Science, Divecha Center for Climate Change and Center for Atmospheric and Oceanic Sciences, Bangalore (India)

    2012-09-15

    A recent modelling study has shown that precipitation and runoff over land would increase when the reflectivity of marine clouds is increased to counter global warming. This implies that large scale albedo enhancement over land could lead to a decrease in runoff over land. In this study, we perform simulations using NCAR CAM3.1 that have implications for Solar Radiation Management geoengineering schemes that increase the albedo over land. We find that an increase in reflectivity over land that mitigates the global mean warming from a doubling of CO{sub 2} leads to a large residual warming in the southern hemisphere and cooling in the northern hemisphere since most of the land is located in northern hemisphere. Precipitation and runoff over land decrease by 13.4 and 22.3%, respectively, because of a large residual sinking motion over land triggered by albedo enhancement over land. Soil water content also declines when albedo over land is enhanced. The simulated magnitude of hydrological changes over land are much larger when compared to changes over oceans in the recent marine cloud albedo enhancement study since the radiative forcing over land needed (-8.2 W m{sup -2}) to counter global mean radiative forcing from a doubling of CO{sub 2} (3.3 W m{sup -2}) is approximately twice the forcing needed over the oceans (-4.2 W m{sup -2}). Our results imply that albedo enhancement over oceans produce climates closer to the unperturbed climate state than do albedo changes on land when the consequences on land hydrology are considered. Our study also has important implications for any intentional or unintentional large scale changes in land surface albedo such as deforestation/afforestation/reforestation, air pollution, and desert and urban albedo modification. (orig.)

  11. Construction of Structure of Indicators of Efficiency of Counteraction to Threats of Information Safety in Interests of the Estimation of Security of Information Processes in Computer Systems

    Directory of Open Access Journals (Sweden)

    A. P. Kurilo

    2010-06-01

    Full Text Available The theorem of system of indicators for an estimation of the security of information processes in the computer systems is formulated and proved. A number of the signs is proved, allowing to consider set of the indicators of efficiency of counteraction to the threats of information safety of the computer systems as the system.

  12. Attacks on the Network Synchronization Systems Counteraction Method Implemented in the Software and Hardware Device «MARSH! 3.0»

    Directory of Open Access Journals (Sweden)

    Dmitry Anatolevich Melnikov

    2013-12-01

    Full Text Available This paper proposes attacks on the network synchronization systems counteraction technique, method, algorithm and realizable aspects. The network synchronization systems are included in information technology systems or networks. This method is implemented in software and hardware device (means «MARSH! 3.0» providing trusted session.

  13. Ubiquitin-specific Protease 11 (USP11) Deubiquitinates Hybrid Small Ubiquitin-like Modifier (SUMO)-Ubiquitin Chains to Counteract RING Finger Protein 4 (RNF4)

    DEFF Research Database (Denmark)

    Hendriks, Ivo A; Schimmel, Joost; Eifler, Karolin

    2015-01-01

    of RNF4 as a counterbalancing factor. In response to DNA damage induced by methyl methanesulfonate, USP11 could counteract RNF4 to inhibit the dissolution of nuclear bodies. Thus, we provide novel insight into cross-talk between ubiquitin and SUMO and uncover USP11 and RNF4 as a balanced SUMO...

  14. Testing the ability of non-methylamine osmolytes present in kidney cells to counteract the deleterious effects of urea on structure, stability and function of proteins.

    Directory of Open Access Journals (Sweden)

    Sheeza Khan

    Full Text Available Human kidney cells are under constant urea stress due to its urine concentrating mechanism. It is believed that the deleterious effect of urea is counteracted by methylamine osmolytes (glycine betaine and glycerophosphocholine present in kidney cells. A question arises: Do the stabilizing osmolytes, non-methylamines (myo-inositol, sorbitol and taurine present in the kidney cells also counteract the deleterious effects of urea? To answer this question, we have measured structure, thermodynamic stability (ΔG D (o and functional activity parameters (K m and k cat of different model proteins in the presence of various concentrations of urea and each non-methylamine osmolyte alone and in combination. We observed that (i for each protein myo-inositol provides perfect counteraction at 1∶2 ([myo-inositol]:[urea] ratio, (ii any concentration of sorbitol fails to refold urea denatured proteins if it is six times less than that of urea, and (iii taurine regulates perfect counteraction in a protein specific manner; 1.5∶2.0, 1.2∶2.0 and 1.0∶2.0 ([taurine]:[urea] ratios for RNase-A, lysozyme and α-lactalbumin, respectively.

  15. Legacy of road salt: Apparent positive larval effects counteracted by negative postmetamorphic effects in wood frogs.

    Science.gov (United States)

    Dananay, Kacey L; Krynak, Katherine L; Krynak, Timothy J; Benard, Michael F

    2015-10-01

    Road salt runoff has potentially large effects on wetland communities, but is typically investigated in short-term laboratory trials. The authors investigated effects of road salt contamination on wood frogs (Rana sylvatica) by combining a field survey with 2 separate experiments. The field survey tested whether wood frog larval traits were associated with road salt contamination in natural wetlands. As conductivity increased, wood frog larvae were less abundant, but those found were larger. In the first experiment of the present study, the authors raised larvae in outdoor artificial ponds under 4 salt concentrations and measured larval vital rates, algal biomass, and zooplankton abundance. Salt significantly increased larval growth, algal biomass, and decreased zooplankton abundance. In the second experiment, the authors raised larvae to metamorphosis in the presence and absence of salt contamination and followed resulting juvenile frogs in terrestrial pens at high and low densities. Exposure to road salt as larvae caused juvenile frogs to have greater mortality in low-density terrestrial environments, possibly because of altered energy allocation, changes in behavior, or reduced immune defenses. The present study suggests that low concentrations of road salt can have positive effects on larval growth yet negative effects on juvenile survival. These results emphasize the importance of testing for effects of contaminants acting through food webs and across multiple life stages as well as the potential for population-level consequences in natural environments. © 2015 SETAC.

  16. Stem nematode counteracts plant resistance of aphids in alfalfa, Medicago sativa.

    Science.gov (United States)

    Ramirez, Ricardo A; Spears, Lori R

    2014-10-01

    Plants are exploited by a diverse community of insect herbivores and phytopathogens that interact indirectly through plant-mediated interactions. Generally, plants are thought to respond to insects and pathogens through different defensive signaling pathways. As plants are selected for resistance to one phytophagous organism type (insect vs. pathogen) in managed systems, it is not clear how this selection may affect community interactions. This study examined the effect of nematode-resistant varieties on aphid (Acyrthosiphon pisum) suppression, and then determined how infection by the stem nematode, Ditylenchus dipsaci, mediated ecological effects on aphids and on plant defense proteins. Four alfalfa (Medicago sativa) varieties were selected with resistance to nematodes only (+,-), aphids only (-,+), nematodes and aphids (+,+), and susceptibility to nematodes and aphids (-,-). Field and greenhouse experiments were conducted to isolate the effect of nematode infection and aphid abundance on each variety. We found that varieties resistant to nematode, regardless of aphid resistance, had the lowest aphid counts, suggesting possible cross-resistance. Aphid abundance, however, increased when plants were exposed to nematodes. Resistant varieties were associated with elevated saponins but these compounds were not affected by insect or pathogen feeding. Concentrations of peroxidases and trypsin inhibitors, however, were increased in nematode resistant varieties when exposed to nematodes and aphids, respectively. The patterns of plant defense were variable, and a combination of resistance traits and changes in nutrient availability may drive positive interactions between nematodes and aphids aboveground.

  17. The anticancer drug tamoxifen counteracts the pathology in a mouse model of duchenne muscular dystrophy.

    Science.gov (United States)

    Dorchies, Olivier M; Reutenauer-Patte, Julie; Dahmane, Elyes; Ismail, Heham M; Petermann, Olivier; Patthey- Vuadens, Ophélie; Comyn, Sophie A; Gayi, Elinam; Piacenza, Tony; Handa, Robert J; Décosterd, Laurent A; Ruegg, Urs T

    2013-02-01

    Duchenne muscular dystrophy (DMD) is a severe disorder characterized by progressive muscle wasting,respiratory and cardiac impairments, and premature death. No treatment exists so far, and the identification of active substances to fight DMD is urgently needed. We found that tamoxifen, a drug used to treat estrogen-dependent breast cancer, caused remarkable improvements of muscle force and of diaphragm and cardiac structure in the mdx(5Cv) mouse model of DMD. Oral tamoxifen treatment from 3 weeks of age for 15 months at a dose of 10 mg/kg/day stabilized myofiber membranes, normalized whole body force, and increased force production and resistance to repeated contractions of the triceps muscle above normal values. Tamoxifen improved the structure of leg muscles and diminished cardiac fibrosis by~ 50%. Tamoxifen also reduced fibrosis in the diaphragm, while increasing its thickness,myofiber count, and myofiber diameter, thereby augmenting by 72% the amount of contractile tissue available for respiratory function. Tamoxifen conferred a markedly slower phenotype to the muscles.Tamoxifen and its metabolites were present in nanomolar concentrations in plasma and muscles,suggesting signaling through high-affinity targets. Interestingly, the estrogen receptors ERa and ERb were several times more abundant in dystrophic than in normal muscles, and tamoxifen normalized the relative abundance of ERb isoforms. Our findings suggest that tamoxifen might be a useful therapy for DMD.

  18. Agrobacterium-mediated genetic transformation of Pogostemon cablin (Blanco) Benth. Using leaf explants: bactericidal effect of leaf extracts and counteracting strategies.

    Science.gov (United States)

    Paul, Anamika; Bakshi, Souvika; Sahoo, Debee Prasad; Kalita, Mohan Chandra; Sahoo, Lingaraj

    2012-04-01

    An optimized protocol for Agrobacterium tumefaciens-mediated transformation of patchouli using leaf disk explants is reported. In vitro antibacterial activity of leaf extracts of the plants revealed Agrobacterium sensitivity to the extracts. Fluorometric assay of bacterial cell viability indicated dose-dependent cytotoxic activity of callus extract against Agrobacterium cells. Addition of 0.1% Tween 20 and 2 g/l L-glutamine to Agrobacterium infection medium counteracted the bactericidal effect and significantly increased the T-DNA delivery to explants. A short preculture of explants for 2 days followed by infection with Agrobacterium in medium containing 150 μM of acetosyringone were found essential for efficient T-DNA delivery. Cocultivation for 3 days at 22 °C in conjunction with other optimized factors resulted in maximum T-DNA delivery. The Agrobacterium-mediated transformation of leaf disk explants were found significantly related to physiological age of the explants, age and origin of the of the donor plant. Leaf explants from second node of the 3-month-old in vivo plants showed highest transformation efficiency (94.3%) revealed by transient GUS expression assay. Plants selected on medium containing 20 mg/l kanamycin showed stable GUS expression in leaves and stem. The elongated shoots readily developed roots on kanamycin-free rooting medium and on transfer to soil, plants were successfully established. Polymerase chain reaction (PCR) and reverse-transcriptase PCR analysis in putative plants confirmed their transgenic nature. The established transformation method should provide new opportunities for the genetic improvement of patchouli for desirable trait.

  19. A jasmonate ZIM-domain protein NaJAZd regulates floral jasmonic acid levels and counteracts flower abscission in Nicotiana attenuata plants.

    Directory of Open Access Journals (Sweden)

    Youngjoo Oh

    Full Text Available Jasmonic acid is an important regulator of plant growth, development and defense. The jasmonate-ZIM domain (JAZ proteins are key regulators in jasmonate signaling ubiquitously present in flowering plants but their functional annotation remains largely incomplete. Recently, we identified 12 putative JAZ proteins in native tobacco, Nicotiana attenuata, and initiated systematic functional characterization of these proteins by reverse genetic approaches. In this report, Nicotiana attenuata plants silenced in the expression of NaJAZd (irJAZd by RNA interference were used to characterize NaJAZd function. Although NaJAZd transcripts were strongly and transiently up-regulated in the rosette leaves by simulated herbivory treatment, we did not observe strong defense-related phenotypes, such as altered herbivore performance or the constitutive accumulation of defense-related secondary metabolites in irJAZd plants compared to wild type plants, both in the glasshouse and the native habitat of Nicotiana attenuata in the Great Basin Desert, Utah, USA. Interestingly, irJAZd plants produced fewer seed capsules than did wild type plants as a result of increased flower abscission in later stages of flower development. The early- and mid-developmental stages of irJAZd flowers had reduced levels of jasmonic acid and jasmonoyl-L-isoleucine, while fully open flowers had normal levels, but these were impaired in NaMYB305 transcript accumulations. Previously, NaMYB305-silenced plants were shown to have strong flower abscission phenotypes and contained lower NECTARIN 1 transcript levels, phenotypes which are copied in irJAZd plants. We propose that the NaJAZd protein is required to counteract flower abscission, possibly by regulating jasmonic acid and jasmonoyl-L-isoleucine levels and/or expression of NaMYB305 gene in Nicotiana attenuata flowers. This novel insight into the function of JAZ proteins in flower and seed development highlights the diversity of functions

  20. Glucagon-like peptide-1 counteracts the detrimental effects of Advanced Glycation End-Products in the pancreatic beta cell line HIT-T 15

    International Nuclear Information System (INIS)

    Puddu, A.; Storace, D.; Durante, A.; Odetti, P.; Viviani, G.L.

    2010-01-01

    Research highlights: → GLP-1 prevents AGEs-induced cell death. → GLP-1 prevents AGEs-induced oxidative stress. → GLP-1 ameliorated AGEs-induced cell dysfunction. → GLP-1 attenuates AGEs-induced RAGE increment. → GLP-1 counteracts AGEs-induced pancreatic cell death and dysfunction. -- Abstract: Advanced Glycation End-Products (AGEs), a group of compounds resulting from the non-enzymatic reaction of reducing sugars with the free amino group of proteins, are implicated in diabetic complications. We previously demonstrated that exposure of the pancreatic islet cell line HIT-T 15 to high concentrations of AGEs significantly decreases cell proliferation and insulin secretion, and affects transcription factors regulating insulin gene transcription. The glucagon-like peptide-1 (GLP-1) is an incretin hormone that increases proinsulin biosynthesis, stimulates insulin secretion, and improves pancreatic beta-cell viability. The aim of this work was to investigate the effects of GLP-1 on the function and viability of HIT-T 15 cells cultured with AGEs. HIT-T 15 cells were cultured for 5 days in presence of AGEs alone, or supplemented with 10 nmol/l GLP-1. Cell viability, insulin secretion, redox balance, and expression of the AGEs receptor (RAGE) were then determined. The results showed that GLP-1 protected beta cell against AGEs-induced cell death preventing both apoptosis and necrosis. Moreover, addition of GLP-1 to the AGEs culture medium restored the redox balance, improved the responsiveness to glucose, and attenuated AGEs-induced RAGE expression. These findings provide evidence that GLP-1 protects beta cells from the dangerous effects of AGEs.

  1. In Vitro Inhibition of Klebsiella pneumoniae by Lactobacillus delbrueckii Subsp. delbrueckii LDD01 (DSM 22106): An Innovative Strategy to Possibly Counteract Such Infections in Humans?

    Science.gov (United States)

    Mogna, Luca; Deidda, Francesca; Nicola, Stefania; Amoruso, Angela; Del Piano, Mario; Mogna, Giovanni

    To determine the in vitro antimicrobial activity of selected Lactobacillus strains isolated from the feces of healthy humans against Klebsiella pneumoniae. Klebsiella is ubiquitous in nature and may colonize the skin, the pharynx, or the gastrointestinal tract of humans. Despite the widespread use of antibiotic molecules with a broad spectrum in hospitalized patients, an increased overall load of klebsiellae as well as the subsequent development of multidrug-resistant strains able to synthesize extended-spectrum beta-lactamase have been registered. These strains are particularly virulent, express capsular-type K55, and have a considerable ability to propagate. The 4 strains Lactobacillus paracasei LPC01 (CNCM I-1390), Lactobacillus rhamnosus LR04 (DSM 16605), Bifidobacterium longum B2274 (DSM 24707), and Lactobacillus delbrueckii subsp. delbrueckii LDD01 (DSM 22106) were tested. The analysis was performed using both a disc-diffusion assay and the broth-dilution procedure, also including an evaluation of the supernatants obtained from a fresh broth culture of each bacterium. L. delbrueckii subsp. delbrueckii LDD01 demonstrated the best inhibitory results among all the tested strains. The antibacterial activity of the supernatant was retained even after treatment with α-amylase and neutralization with NaOH 1N, thus suggesting the protein structure of the inhibitory molecule. In contrast, it was completely lost after treatment with proteinase K. Overall results suggest that the inhibitory effect of L. delbrueckii subsp. delbrueckii LDD01 should be attributed to the production of a bacteriocin. This strain may be prospectively useful for strengthening probiotic formulations and possibly counteract infections by K. pneumoniae in humans.

  2. A pandemic in disguise: Zika virus vaccine development and counteractive measures analysis

    Directory of Open Access Journals (Sweden)

    Owais Fazal

    2016-01-01

    Full Text Available In recent times, Zika virus has engendered concerns throughout the world, prompting the World Health Organization to promote the virus to epidemic status. This dramatic rise to prominence demands comprehensive research oriented towards effectively controlling the spread of this virulent disease. Despite the influx of information afforded by modern technology regarding the virus, there are yet to be licensed medical countermeasures (vaccines, therapies or preventive drugs available for Zika virus infection and disease. Thus, diverting sizable funds towards prospective Zika virus vaccine candidates as well as appropriately educating the modern healthcare worker regarding the epidemiology of Zika virus is becoming increasingly imperative. Fortunately, a multitude of researchers are working towards instituting pragmatic measures directed towards limiting Zika virus′s spread in an interconnected global climate.

  3. Notch inhibition counteracts Paneth cell death in absence of caspase-8.

    Science.gov (United States)

    Jeon, M K; Kaemmerer, E; Schneider, U; Schiffer, M; Klaus, C; Hennings, J; Clahsen, T; Ackerstaff, T; Niggemann, M; Schippers, A; Longerich, T; Sellge, G; Trautwein, C; Wagner, N; Liedtke, C; Gassler, N

    2018-05-16

    Opposing activities of Notch and Wnt signaling regulate mucosal barrier homeostasis and differentiation of intestinal epithelial cells. Specifically, Wnt activity is essential for differentiation of secretory cells including Wnt3-producing Paneth cells, whereas Notch signaling strongly promotes generation of absorptive cells. Loss of caspase-8 in intestinal epithelium (casp8 ∆int ) is associated with fulminant epithelial necroptosis, severe Paneth cell death, secondary intestinal inflammation, and an increase in Notch activity. Here, we found that pharmacological Notch inhibition with dibenzazepine (DBZ) is able to essentially rescue the loss of Paneth cells, deescalate the inflammatory phenotype, and reduce intestinal permeability in casp8 ∆int mice. The secretory cell metaplasia in DBZ-treated casp8 ∆int animals is proliferative, indicating for Notch activities partially insensitive to gamma-secretase inhibition in a casp8 ∆int background. Our data suggest that casp8 acts in the intestinal Notch network.

  4. Forecasting hourly patient visits in the emergency department to counteract crowding

    DEFF Research Database (Denmark)

    Hertzum, Morten

    2017-01-01

    visits. The data for 2012-2014 were used to create linear regression models, autoregressive integrated moving average (ARIMA) models, and – for purposes of comparison – naïve models of hourly patient arrivals and ED occupancy. Using the models, patient arrivals and ED occupancy were forecasted for every...... hour of January 2015. Results: Hourly patient arrivals were forecasted with a mean percentage error of 47-58% (regression), 49-58% (ARIMA), and 60-76% (naïve). Increasing the forecasting interval decreased the mean percentage error. ED occupancy was forecasted with better accuracy by ARIMA than...... regression models. With ARIMA the mean percentage error of the forecasts of the hourly ED occupancy was 69-73% for three of the EDs and 101% for the last ED. Factors beyond calendar variables might possibly have improved the models of ED occupancy, provided that information about these factors had been...

  5. LDL cholesterol counteracts the antitumour effect of tyrosine kinase inhibitors against renal cell carcinoma.

    Science.gov (United States)

    Naito, Sei; Makhov, Peter; Astsaturov, Igor; Golovine, Konstantin; Tulin, Alexei; Kutikov, Alexander; Uzzo, Robert G; Kolenko, Vladimir M

    2017-04-25

    Treatment with tyrosine kinase inhibitors (TKIs) significantly improves survival of patients with renal cell carcinoma (RCC). However, about one-quarter of the RCC patients are primarily refractory to treatment with TKIs. We examined viability of RCC and endothelial cells treated with low-density lipoprotein (LDL) and/or TKIs. Next, we validated the potential role of PI3K/AKT signalling in LDL-mediated TKI resistance. Finally, we examined the effect of a high-fat/high-cholesterol diet on the response of RCC xenograft tumours to sunitinib. The addition of LDL cholesterol increases activation of PI3K/AKT signalling and compromises the antitumour efficacy of TKIs against RCC and endothelial cells. Furthermore, RCC xenograft tumours resist TKIs in mice fed a high-fat/high-cholesterol diet. The ability of renal tumours to maintain their cholesterol homoeostasis may be a critical component of TKI resistance in RCC patients.

  6. Sorbitol counteracts high hydrostatic pressure-induced denaturation of inulin fructotransferase.

    Science.gov (United States)

    Li, Yungao; Miao, Ming; Liu, Miao; Jiang, Bo; Zhang, Tao; Chen, Xiangyin

    2014-09-01

    Inulin fructotransferase (IFTase), a novel hydrolase for inulin, was exposed to high hydrostatic pressure (HHP) at 400 and 600 MPa for 15 min in the presence or absence of sorbitol. Sorbitol protected the enzyme against HHP-induced activity loss. The relative residual activity increased nearly 3.1- and 3.8-fold in the presence of 3 mol/L sorbitol under 400 MPa and 600 MPa for 15 min, respectively. Circular dichroism results indicated that the original chaotic unfolding conformation of the enzyme under HHP shifted toward more ordered and impact with 3 mol/L sorbitol. Fluorescence and UV spectra results suggested that sorbitol prevented partially the unfolding of the enzyme and stabilized the conformation under high pressure. These results might be attributed to the binding of sorbitol on the surface of IFTase to rearrange and strengthen intra- and intermolecular hydrogen bonds. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Astragaloside IV attenuates experimental autoimmune encephalomyelitis of mice by counteracting oxidative stress at multiple levels.

    Directory of Open Access Journals (Sweden)

    Yixin He

    Full Text Available Multiple sclerosis (MS is a chronic autoimmune neuroinflammatory disease found mostly in young adults in the western world. Oxidative stress induced neuronal apoptosis plays an important role in the pathogenesis of MS. In current study, astragaloside IV (ASI, a natural saponin molecule isolated from Astragalus membranceus, given at 20 mg/kg daily attenuated the severity of experimental autoimmune encephalomyelitis (EAE in mice significantly. Further studies disclosed that ASI treatment inhibited the increase of ROS and pro-inflammatory cytokine levels, down-regulation of SOD and GSH-Px activities, and elevation of iNOS, p53 and phosphorylated tau in central nervous system (CNS as well as the leakage of BBB of EAE mice. Meanwhile, the decreased ratio of Bcl-2/Bax was reversed by ASI. Moreover, ASI regulated T-cell differentiation and infiltration into CNS. In neuroblast SH-SY5Y cells, ASI dose-dependently reduced cellular ROS level and phosphorylation of tau in response to hydrogen peroxide challenge by modulation of Bcl-2/Bax ratio. ASI also inhibited activation of microglia both in vivo and in vitro. iNOS up-regulation induced by IFNγ stimulation was abolished by ASI dose-dependently in BV-2 cells. In summary, ASI prevented the severity of EAE progression possibly by counterbalancing oxidative stress and its effects via reduction of cellular ROS level, enhancement of antioxidant defense system, increase of anti-apoptotic and anti-inflammatory pathways, as well as modulation of T-cell differentiation and infiltration into CNS. The study suggested ASI may be effective for clinical therapy/prevention of MS.

  8. Astragaloside IV attenuates experimental autoimmune encephalomyelitis of mice by counteracting oxidative stress at multiple levels.

    Science.gov (United States)

    He, Yixin; Du, Min; Gao, Yan; Liu, Hongshuai; Wang, Hongwei; Wu, Xiaojun; Wang, Zhengtao

    2013-01-01

    Multiple sclerosis (MS) is a chronic autoimmune neuroinflammatory disease found mostly in young adults in the western world. Oxidative stress induced neuronal apoptosis plays an important role in the pathogenesis of MS. In current study, astragaloside IV (ASI), a natural saponin molecule isolated from Astragalus membranceus, given at 20 mg/kg daily attenuated the severity of experimental autoimmune encephalomyelitis (EAE) in mice significantly. Further studies disclosed that ASI treatment inhibited the increase of ROS and pro-inflammatory cytokine levels, down-regulation of SOD and GSH-Px activities, and elevation of iNOS, p53 and phosphorylated tau in central nervous system (CNS) as well as the leakage of BBB of EAE mice. Meanwhile, the decreased ratio of Bcl-2/Bax was reversed by ASI. Moreover, ASI regulated T-cell differentiation and infiltration into CNS. In neuroblast SH-SY5Y cells, ASI dose-dependently reduced cellular ROS level and phosphorylation of tau in response to hydrogen peroxide challenge by modulation of Bcl-2/Bax ratio. ASI also inhibited activation of microglia both in vivo and in vitro. iNOS up-regulation induced by IFNγ stimulation was abolished by ASI dose-dependently in BV-2 cells. In summary, ASI prevented the severity of EAE progression possibly by counterbalancing oxidative stress and its effects via reduction of cellular ROS level, enhancement of antioxidant defense system, increase of anti-apoptotic and anti-inflammatory pathways, as well as modulation of T-cell differentiation and infiltration into CNS. The study suggested ASI may be effective for clinical therapy/prevention of MS.

  9. Helminth antigens counteract a rapid high-fat diet-induced decrease in adipose tissue eosinophils.

    Science.gov (United States)

    van den Berg, Susan M; van Dam, Andrea D; Kusters, Pascal J H; Beckers, Linda; den Toom, Myrthe; van der Velden, Saskia; Van den Bossche, Jan; van Die, Irma; Boon, Mariëtte R; Rensen, Patrick C N; Lutgens, Esther; de Winther, Menno P J

    2017-10-01

    Brown adipose tissue (BAT) activation and white adipose tissue (WAT) beiging can increase energy expenditure and have the potential to reduce obesity and associated diseases. The immune system is a potential target in mediating brown and beige adipocyte activation. Type 2 and anti-inflammatory immune cells contribute to metabolic homeostasis within lean WAT, with a prominent role for eosinophils and interleukin (IL)-4-induced anti-inflammatory macrophages. We determined eosinophil numbers in epididymal WAT (EpAT), subcutaneous WAT (ScAT) and BAT after 1 day, 3 days or 1 week of high-fat diet (HFD) feeding in C57Bl/6 mice. One day of HFD resulted in a rapid drop in eosinophil numbers in EpAT and BAT, and after 3 days, in ScAT. In an attempt to restore this HFD-induced drop in adipose tissue eosinophils, we treated 1-week HFD-fed mice with helminth antigens from Schistosoma mansoni or Trichuris suis and evaluated whether the well-known protective metabolic effects of helminth antigens involves BAT activation or beiging. Indeed, antigens of both helminth species induced high numbers of eosinophils in EpAT, but failed to induce beiging. In ScAT, Schistosoma mansoni antigens induced mild eosinophilia, which was accompanied by slightly more beiging. No effects were observed in BAT. To study type 2 responses on brown adipocytes directly, T37i cells were stimulated with IL-4. This increased Ucp1 expression and strongly induced the production of eosinophil chemoattractant CCL11 (+26-fold), revealing that brown adipocytes themselves can attract eosinophils. Our findings indicate that helminth antigen-induced eosinophilia fails to induce profound beiging of white adipocytes. © 2017 Society for Endocrinology.

  10. Glutamate Induced Thermal Equilibrium Intermediate and Counteracting Effect on Chemical Denaturation of Proteins.

    Science.gov (United States)

    Anumalla, Bramhini; Prabhu, N Prakash

    2018-01-25

    When organisms are subjected to stress conditions, one of their adaptive responses is accumulation of small organic molecules called osmolytes. These osmolytes affect the structure and stability of the biological macromolecules including proteins. The present study examines the effect of a negatively charged amino acid osmolyte, glutamate (Glu), on two model proteins, ribonuclease A (RNase A) and α-lactalbumin (α-LA), which have positive and negative surface charges at pH 7, respectively. These proteins follow two-state unfolding transitions during both heat and chemical induced denaturation processes. The addition of Glu stabilizes the proteins against temperature and induces an early equilibrium intermediate during unfolding. The stability is found to be enthalpy-driven, and the free energy of stabilization is more for α-LA compared to RNase A. The decrease in the partial molar volume and compressibility of both of the proteins in the presence of Glu suggests that the proteins attain a more compact state through surface hydration which could provide a more stable conformation. This is also supported by molecule dynamic simulation studies which demonstrate that the water density around the proteins is increased upon the addition of Glu. Further, the intermediates could be completely destabilized by lower concentrations (∼0.5 M) of guanidinium chloride and salt. However, urea subverts the Glu-induced intermediate formed by α-LA, whereas it only slightly destabilizes in the case of RNase A which has a positive surface charge and could possess charge-charge interactions with Glu. This suggests that, apart from hydration, columbic interactions might also contribute to the stability of the intermediate. Gdm-induced denaturation of RNase A and α-LA in the absence and the presence of Glu at different temperatures was carried out. These results also show the Glu-induced stabilization of both of the proteins; however, all of the unfolding transitions followed two

  11. Vitamin K supplementation increases vitamin K tissue levels but fails to counteract ectopic calcification in a mouse model for pseudoxanthoma elasticum

    NARCIS (Netherlands)

    Gorgels, Theo G. M. F.; Waarsing, Jan H.; Herfs, Marjolein; Versteeg, Daniëlle; Schoensiegel, Frank; Sato, Toshiro; Schlingemann, Reinier O.; Ivandic, Boris; Vermeer, Cees; Schurgers, Leon J.; Bergen, Arthur A. B.

    2011-01-01

    Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder in which calcification of connective tissue leads to pathology in skin, eye and blood vessels. PXE is caused by mutations in ABCC6. High expression of this transporter in the basolateral hepatocyte membrane suggests that it secretes

  12. Vitamin K supplementation increases vitamin K tissue levels but fails to counteract ectopic calcification in a mouse model for pseudoxanthoma elasticum

    NARCIS (Netherlands)

    T.G.M.F. Gorgels (Theo); J.H. Waarsing (Jan); M. Herfs (Marjolein); D. Versteeg (Daniëlle); F. Schoensiegel (Frank); T. Sato (Toshiro); R.O. Schlingemann (Reinier); B. Ivandic (Boris); C. Vermeer (Cees); L.J. Schurgers (Leon); A.A.B. Bergen (Arthur)

    2011-01-01

    textabstractPseudoxanthoma elasticum (PXE) is an autosomal recessive disorder in which calcification of connective tissue leads to pathology in skin, eye and blood vessels. PXE is caused by mutations in ABCC6. High expression of this transporter in the basolateral hepatocyte membrane suggests that

  13. Exercise counteracts aging-related memory impairment: a potential role for the astrocytic metabolic shuttle

    Directory of Open Access Journals (Sweden)

    Sheng-Feng eTsai

    2016-03-01

    Full Text Available Age-related cognitive impairment has become one of the most common health threats in many countries. The biological substrate of cognition is the interconnection of neurons to form complex information processing networks. Experience-based alterations in the activities of these information processing networks lead to neuroadaptation, which is physically represented at the cellular level as synaptic plasticity. Although synaptic plasticity is known to be affected by aging, the underlying molecular mechanisms are not well described. Astrocytes, a glial cell type that is infrequently investigated in cognitive science, have emerged as energy suppliers which are necessary for meeting the abundant energy demand resulting from glutamatergic synaptic activity. Moreover, the concerted action of an astrocyte-neuron metabolic shuttle is essential for cognitive function; whereas, energetic incoordination between astrocytes and neurons may contribute to cognitive impairment. Whether altered function of the astrocyte-neuron metabolic shuttle links aging to reduced synaptic plasticity is unexplored. However, accumulated evidence documents significant beneficial effects of long-term, regular exercise on cognition and synaptic plasticity. Furthermore, exercise increases the effectiveness of astrocyte-neuron metabolic shuttle by upregulation of astrocytic lactate transporter levels. This review summarizes previous findings related to the neuronal activity-dependent astrocyte-neuron metabolic shuttle. Moreover, we discuss how aging and exercise may shape the astrocyte-neuron metabolic shuttle in cognition-associated brain areas.

  14. Meditation and successful aging: can meditative practices counteract age-related cognitive decline?

    Science.gov (United States)

    Sperduti, Marco; Makowski, Dominique; Blondé, Philippe; Piolino, Pascale

    2017-06-01

    Life expectancy is constantly increasing in the developed countries due to medical, hygiene and socio-economic advances. Unfortunately, a longer life not always corresponds to a healthier life. Indeed, aging is associated with growing risk factors for illness associated with societal conditions (isolation, maltreatment), and neurodegenerative diseases. Even normal aging is associated with a cognitive decline that can hinder independence and quality of life of elderly. Thus, one major societal challenge is to build policies that support people of all ages to maintain a maximum health and functional capacity throughout their lives. Meditation could be a promising intervention in contrasting the negative effects of aging. Indeed, it has been shown to enhance cognitive efficiency in several domains, such as attention and executive functions in young adults. Nevertheless, whether these effects extend to old participants is still a matter of debate. Few studies have directly investigated this issue, reporting encouraging results in a large panel of cognitive functions, such as: attention, executive functions and memory. However, a final conclusion about the causal role of meditation and the generalization of these results is made difficult due to several methodological limitations. We propose a roadmap for future studies to pass these limitations with the hope that the present work would contribute to the development of the young research field of meditation in gerontology.

  15. Nanosystems based on siRNA silencing HuR expression counteract diabetic retinopathy in rat.

    Science.gov (United States)

    Amadio, Marialaura; Pascale, Alessia; Cupri, Sarha; Pignatello, Rosario; Osera, Cecilia; D Agata, Velia; D Amico, Agata Grazia; Leggio, Gian Marco; Ruozi, Barbara; Govoni, Stefano; Drago, Filippo; Bucolo, Claudio

    2016-09-01

    We evaluated whether specifically and directly targeting human antigen R (HuR), a member of embryonic lethal abnormal vision (ELAV) proteins family, may represent a new potential therapeutic strategy to manage diabetic retinopathy. Nanosystems loaded with siRNA silencing HuR expression (lipoplexes), consisting of solid lipid nanoparticles (SLN) and liposomes (SUV) were prepared. Photon correlation spectroscopy analysis, Zeta potential measurement and atomic force microscopy (AFM) studies were carried out to characterize the complexation of siRNA with the lipid nanocarriers. Nanosystems were evaluated by using AFM and scanning electron microscopy. The lipoplexes were injected into the eye of streptozotocin (STZ)-induced diabetic rats. Retinal HuR and VEGF levels were detected by Western blot and ELISA, respectively. Retinal histology was also carried out. The results demonstrated that retinal HuR and VEGF are significantly increased in STZ-rats and are blunted by HuR siRNA treatment. Lipoplexes with a weak positive surface charge and with a 4:1 N/P (cationic lipid nitrogen to siRNA phosphate) ratio exert a better transfection efficiency, significantly dumping retinal HuR and VEGF levels. In conclusion, we demonstrated that siRNA can be efficiently delivered into the rat retina using lipid-based nanocarriers, and some of the lipoplexes loaded with siRNA silencing HuR expression are potential candidates to manage retinal diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. The European Union Counteraction To Israel's Settlement Policy In The Occupied Arab Territories: Myths And Realities

    Directory of Open Access Journals (Sweden)

    Alexander V. Krylov

    2014-01-01

    Full Text Available More than 50 years the European Union member states (the European Economic Community up to 1993 maintain a special relations with Israel particularly in the trade sphere. Only in 2014 the export of Israeli products to Europe increased by 3%, amounting in absolute terms to a third of total exports of Israel. At the same time, the position of the EU with regard to the Palestinian-Israeli conflict is clearly contrary to the real character of the mutual economic, scientific and technical cooperation. After the failure in 2001 of the Palestinian-Israeli negotiations aimed to reach a «Final-Status Agreement» in accordance with the Oslo Accords, the European Union made several attempts to limit the European market penetration of the Israeli products originating from the occupied territories (the West Bank, Gaza Strip, East Jerusalem and the Golan Heights. However, as can be seen from the contents of the article, there is no consensus between the EU member states with regard to the Israeli settlement policy. The study argues that all the decisions made so far in the European Union to limit Israeli export or reduce crediting of programs for scientific and technical cooperation used to be of declarative or vague character.

  17. 21st Century drought-related fires counteract the decline of Amazon deforestation carbon emissions.

    Science.gov (United States)

    Aragão, Luiz E O C; Anderson, Liana O; Fonseca, Marisa G; Rosan, Thais M; Vedovato, Laura B; Wagner, Fabien H; Silva, Camila V J; Silva Junior, Celso H L; Arai, Egidio; Aguiar, Ana P; Barlow, Jos; Berenguer, Erika; Deeter, Merritt N; Domingues, Lucas G; Gatti, Luciana; Gloor, Manuel; Malhi, Yadvinder; Marengo, Jose A; Miller, John B; Phillips, Oliver L; Saatchi, Sassan

    2018-02-13

    Tropical carbon emissions are largely derived from direct forest clearing processes. Yet, emissions from drought-induced forest fires are, usually, not included in national-level carbon emission inventories. Here we examine Brazilian Amazon drought impacts on fire incidence and associated forest fire carbon emissions over the period 2003-2015. We show that despite a 76% decline in deforestation rates over the past 13 years, fire incidence increased by 36% during the 2015 drought compared to the preceding 12 years. The 2015 drought had the largest ever ratio of active fire counts to deforestation, with active fires occurring over an area of 799,293 km 2 . Gross emissions from forest fires (989 ± 504 Tg CO 2 year -1 ) alone are more than half as great as those from old-growth forest deforestation during drought years. We conclude that carbon emission inventories intended for accounting and developing policies need to take account of substantial forest fire emissions not associated to the deforestation process.

  18. Calcium permeability of the T lymphocyte plasma membrane: counteraction of phorbol ester and A23187

    Energy Technology Data Exchange (ETDEWEB)

    Csermely, P.; Szamel, M.; Somogyi, J.

    1986-01-01

    The intracellular calcium concentration (Ca/sub i/) of T lymphocytes was measured using the fluorescent indicator quin2. Different ionophores effectively enhanced the Ca permeability of the plasma membrane. The effective concentration of the ionophores required for permeabilization increased in the order of ionomycin, A23187 and X537-A (lasalocid-A). 12-0-tetradecanoyl-phorbol-13-acetate (TPA) in submicromolar concentrations did not change Ca/sub i/. The addition of TPA immediately before the A23187-permeabilization did not alter the Ca ionophoretic effect of A23187. However, prolonged incubation with TPA decreased the efficiency of A23187 permeabilizing the plasma membrane for calcium ions. This effect was concentration and time dependent, being maximal at TPA concentrations higher than 10 nM with a preincubation time of 1.5 hours. TPA induced relative A23187 insensitivity is most probably not due to a direct effect of TPA on the ionophore as it is concentration and time dependent. Moreover the fluorescence and fluorescence polarization of A23187 as well as the energy transfer between the tryptophan groups of the membrane proteins and A23187 showed no significant change during incubation with TPA. These results indicate that membrane fluidity changes or A23187 immobilization also do not play a prominent role in the explanation of the phenomenon. However the supposed intracellular heavy metal content of T lymphocyte might be a possible source of the TPA induced relative insensitization towards A23187.

  19. Bovine lactoferrin counteracts Toll-like receptor mediated activation signals in antigen presenting cells.

    Directory of Open Access Journals (Sweden)

    Patrizia Puddu

    Full Text Available Lactoferrin (LF, a key element in mammalian immune system, plays pivotal roles in host defence against infection and excessive inflammation. Its protective effects range from direct antimicrobial activities against a large panel of microbes, including bacteria, viruses, fungi and parasites, to antinflammatory and anticancer activities. In this study, we show that monocyte-derived dendritic cells (MD-DCs generated in the presence of bovine LF (bLF fail to undergo activation by up-modulating CD83, co-stimulatory and major histocompatibility complex molecules, and cytokine/chemokine secretion. Moreover, these cells are weak activators of T cell proliferation and retain antigen uptake activity. Consistent with an impaired maturation, bLF-MD-DC primed T lymphocytes exhibit a functional unresponsiveness characterized by reduced expression of CD154 and impaired expression of IFN-γ and IL-2. The observed imunosuppressive effects correlate with an increased expression of molecules with negative regulatory functions (i.e. immunoglobulin-like transcript 3 and programmed death ligand 1, indoleamine 2,3-dioxygenase, and suppressor of cytokine signaling-3. Interestingly, bLF-MD-DCs produce IL-6 and exhibit constitutive signal transducer and activator of transcription 3 activation. Conversely, bLF exposure of already differentiated MD-DCs completely fails to induce IL-6, and partially inhibits Toll-like receptor (TLR agonist-induced activation. Cell-specific differences in bLF internalization likely account for the distinct response elicited by bLF in monocytes versus immature DCs, providing a mechanistic base for its multiple effects. These results indicate that bLF exerts a potent anti-inflammatory activity by skewing monocyte differentiation into DCs with impaired capacity to undergo activation and to promote Th1 responses. Overall, these bLF-mediated effects may represent a strategy to block excessive DC activation upon TLR-induced inflammation, adding

  20. Neonatal dexamethasone accelerates spreading depression in the rat, and antioxidant vitamins counteract this effect.

    Science.gov (United States)

    Lopes-de-Morais, Andréia Albuquerque Cunha; Mendes-da-Silva, Rosângela Figueiredo; dos-Santos, Eryka Maria; Guedes, Rubem Carlos Araújo

    2014-12-03

    The use of dexamethasone (Dex) to treat chronic lung disease in preterm infants may produce adverse effects in the developing brain. Here, we evaluated the effects of neonatal Dex on the propagation of cortical spreading depression (CSD), and tested the action of vitamins C and E against the effect of Dex. Five groups of Wistar rats received, respectively: [1] no treatment (Naïve); [2] Vehicle (V); [3] tapering doses of Dex (Dex; 0.5mg/kg, 0.3mg/kg, and 0.1mg/kg) on postnatal day (PND) 1-3; [4] Dex plus 200mg/kg vitamin C and 100mg/kg vitamin E (DexCE); [5] only vitamins C and E (CE). Vehicle and vitamins were administered on PND 1-6. CSD was recorded after the pups reached maturity (PND 60-70). The Dex-treated group presented with higher CSD velocities (mean values ± SD, in mm/min: 4.14 ± 0.22, n=10) compared with the control groups (Naïve: 3.52 ± 0.13, n=8; V: 3.57 ± 0.18, n=10; CE: 3.51 ± 0.24, n=10; pVitamins C and E antagonized this effect (DexCE group; CSD velocity: 3.43 ± 0.12, n=9). No intergroup difference was observed concerning P-wave amplitude and duration. In all groups, after the cortex underwent CSD, the electrocorticogram (ECoG) amplitude increased approximately 50% compared with the baseline amplitude for the same animal (CSD-induced ECoG potentiation); however, no intergroup difference was observed. Data suggest that coadministration of antioxidant vitamins with Dex may be a helpful therapeutic strategy to reduce brain adverse effects of dexamethasone. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Immunotherapy counteracting the immuno-depressive effect of radio and chemotherapy

    International Nuclear Information System (INIS)

    Robinson, E.; Bartal, A.; Cohen, Y.; Mekori, T.

    1977-01-01

    Surgery, radiotherapy and chemotherapy effect cures in a portion of cancer patients, but these treatments depress the immune system of the host. The purpose of our work was to find whether immunotherapy would abolish the depressive effect of the conventional treatment and thereby increase the percentage of cancer patients cured from their disease. The immunotherapeutic agent used was MER, a methanol extraction residue of the antituberculosis vaccine BCG. All patients had histologically proven neoplasia. The immunological responsiveness of the patients was evaluated before and after radiotherapy, chemotherapy and each MER treatment. The following immunological parameters were followed: (i) cutaneous delayed hypersensitivity to 3 recal antigens (PPD, SK-SD and Candidine); (ii) in vitro lymphocytic transformation to PHA and to the 3 above mentioned antigens. The patients were randomized into two groups. One group receiving injections of MER and the second acting as a control group. MER had no serious side effects and was well tolerated in most of the patients. The cutaneous reactivity became stronger and the lymphocytic stimulation index became higher after MER treatment. 51 patients with advanced lung cancer entered the trial. 29 were treated by MER after radiotherapy and/or chemotherapy and 22 control patients received only conventional therapy. There was no statistical significant difference in the survival between both groups, but it seems that in patients with locally advanced disease the survival was better in the MER group. MER treated group had less distant metastases which is in accord with the theory that immunotherapy is more effective in small tumours. Evidence points to the importance of the immune response in controlling the progression of malignant disease. Therefore, for neoplasia which cannot be controlled by surgery and/or radiotherapy and/or chemotherapy immunotherapy should be considered. (author)

  2. Counteracting foaming caused by lipids or proteins in biogas reactors using rapeseed oil or oleic acid as antifoaming agents.

    Science.gov (United States)

    Kougias, P G; Boe, K; Einarsdottir, E S; Angelidaki, I

    2015-08-01

    Foaming is one of the major operational problems in biogas plants, and dealing with foaming incidents is still based on empirical practices. Various types of antifoams are used arbitrarily to combat foaming in biogas plants, but without any scientific support this action can lead to serious deterioration of the methanogenic process. Many commercial antifoams are derivatives of fatty acids or oils. However, it is well known that lipids can induce foaming in manure based biogas plants. This study aimed to elucidate the effect of rapeseed oil and oleic acid on foam reduction and process performance in biogas reactors fed with protein or lipid rich substrates. The results showed that both antifoams efficiently suppressed foaming. Moreover rapeseed oil resulted in stimulation of the biogas production. Finally, it was reckoned that the chemical structure of lipids, and more specifically their carboxylic ends, is responsible for their foam promoting or foam counteracting behaviour. Thus, it was concluded that the fatty acids and oils could suppress foaming, while salt of fatty acids could generate foam. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. The Replisome-Coupled E3 Ubiquitin Ligase Rtt101Mms22 Counteracts Mrc1 Function to Tolerate Genotoxic Stress.

    Directory of Open Access Journals (Sweden)

    Raymond Buser

    2016-02-01

    Full Text Available Faithful DNA replication and repair requires the activity of cullin 4-based E3 ubiquitin ligases (CRL4, but the underlying mechanisms remain poorly understood. The budding yeast Cul4 homologue, Rtt101, in complex with the linker Mms1 and the putative substrate adaptor Mms22 promotes progression of replication forks through damaged DNA. Here we characterized the interactome of Mms22 and found that the Rtt101(Mms22 ligase associates with the replisome progression complex during S-phase via the amino-terminal WD40 domain of Ctf4. Moreover, genetic screening for suppressors of the genotoxic sensitivity of rtt101Δ cells identified a cluster of replication proteins, among them a component of the fork protection complex, Mrc1. In contrast to rtt101Δ and mms22Δ cells, mrc1Δ rtt101Δ and mrc1Δ mms22Δ double mutants complete DNA replication upon replication stress by facilitating the repair/restart of stalled replication forks using a Rad52-dependent mechanism. Our results suggest that the Rtt101(Mms22 E3 ligase does not induce Mrc1 degradation, but specifically counteracts Mrc1's replicative function, possibly by modulating its interaction with the CMG (Cdc45-MCM-GINS complex at stalled forks.

  4. The novel dehydroepiandrosterone (DHEA) derivative BNN27 counteracts delay-dependent and scopolamine-induced recognition memory deficits in rats.

    Science.gov (United States)

    Pitsikas, Nikolaos; Gravanis, Achille

    2017-04-01

    Experimental evidence indicates that the neurosteroids dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) are involved in cognition. BNN27 is a novel 17C spiroepoxy-DHEA derivative, which devoid of steroidogenic activity. The neuroprotective effects of BNN27 have been recently reported. The present study was designed to investigate the effects of BNN27 on recognition memory in rats. For this purpose, the novel object task (NOT), a procedure assessing non-spatial recognition memory and the novel location task (NLT), a procedure evaluating spatial recognition memory were used. Intraperitoneal (i.p.) administration of BNN27 (3 and 10mg/kg) antagonized delay-dependent deficits in the NOT in the normal rat, suggesting that this DHEA derivative affected acquisition, storage and retrieval of information. In addition, BNN27 (3 and 10mg/kg, i.p.) counteracted the scopolamine [0.2mg/kg, subcutaneously (s.c.)]-induced non-spatial and spatial recognition memory deficits. These findings suggest that BNN27 may modulate different aspects of recognition memory, potentially interacting with the cholinergic system, relevant to cognition. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Model Dependency of TMAO's Counteracting Effect Against Action of Urea: Kast Model versus Osmotic Model of TMAO.

    Science.gov (United States)

    Borgohain, Gargi; Paul, Sandip

    2016-03-10

    Classical molecular dynamics simulation of GB1 peptide (a 16-residue β-hairpin) in different osmotic environments is studied. Urea is used for denaturation of the peptide, and trimethylamine-N-oxide (TMAO) is used to offset the effect of urea. Protein-urea electrostatic interactions are found to play a major role in protein-denaturation. To emphasize on protein protecting action of TMAO against urea, two different models of TMAO are used, viz., the Kast model and the Osmotic model. We observe that the Osmotic model of TMAO gives the best protection to counteract urea's action when used in ratio 1:2 of urea:TMAO (i.e., reverse ratio). This is because the presence of TMAO makes urea-protein electrostatic interactions more unfavorable. Preferential solvation of TMAO molecules by urea (and water) molecules is also observed, which causes depletion in the number of urea molecules in the vicinity of the protein. The calculations of intraprotein hydrogen bonds between different residues of protein further reveal the breaking of backbone hydrogen bonds of residues 2 and 15 in the presence of urea, and the same is preserved in the presence of TMAO. Free energy landscapes show that the narrowest distribution is obtained for the osmotic TMAO model when used in reverse ratio.

  6. Hypoxic resistance of KRAS mutant tumor cells to 3-Bromopyruvate is counteracted by Prima-1 and reversed by N-acetylcysteine.

    Science.gov (United States)

    Orue, Andrea; Chavez, Valery; Strasberg-Rieber, Mary; Rieber, Manuel

    2016-11-18

    The metabolic inhibitor 3-bromopyruvate (3-BrPA) is a promising anti-cancer alkylating agent, shown to inhibit growth of some colorectal carcinoma with KRAS mutation. Recently, we demonstrated increased resistance to 3-BrPA in wt p53 tumor cells compared to those with p53 silencing or mutation. Since hypoxic microenvironments select for tumor cells with diminished therapeutic response, we investigated whether hypoxia unequally increases resistance to 3-BrPA in wt p53 MelJuso melanoma harbouring (Q61L)-mutant NRAS and wt BRAF, C8161 melanoma with (G12D)-mutant KRAS (G464E)-mutant BRAF, and A549 lung carcinoma with a KRAS (G12S)-mutation. Since hypoxia increases the toxicity of the p53 activator, Prima-1 against breast cancer cells irrespective of their p53 status, we also investigated whether Prima-1 reversed hypoxic resistance to 3-BrPA. In contrast to the high susceptibility of hypoxic mutant NRAS MelJuso cells to 3-BrPA or Prima-1, KRAS mutant C8161 and A549 cells revealed hypoxic resistance to 3-BrPA counteracted by Prima-1. In A549 cells, Prima-1 increased p21CDKN1mRNA, and reciprocally inhibited mRNA expression of the SLC2A1-GLUT1 glucose transporter-1 and ALDH1A1, gene linked to detoxification and stem cell properties. 3-BrPA lowered CAIX and VEGF mRNA expression. Death from joint Prima-1 and 3-BrPA treatment in KRAS mutant A549 and C8161 cells seemed mediated by potentiating oxidative stress, since it was antagonized by the anti-oxidant and glutathione precursor N-acetylcysteine. This report is the first to show that Prima-1 kills hypoxic wt p53 KRAS-mutant cells resistant to 3-BrPA, partly by decreasing GLUT-1 expression and exacerbating pro-oxidant stress.

  7. Listening to Music during Warming-Up Counteracts the Negative Effects of Ramadan Observance on Short-Term Maximal Performance

    Science.gov (United States)

    Baklouti, Hana; Chtourou, Hamdi; Driss, Tarak; Chaouachi, Anis; Chamari, Karim; Souissi, Nizar

    2015-01-01

    Aim The aim of the present study was to examine whether listening to music during warming-up might influence short-term maximal performance (STMP), cognitive anxiety, self-confidence, and enjoyment during Ramadan, and whether these affects might predict STMP. Methods Nine male physical education students (age: 21 ± 1.1 years; height: 1.8 ± 0.04 m; body mass: 83 ± 5 kg) volunteered to participate in the present study. A within-subjects design consisted of four experimental sessions: Two sessions occurred one week before Ramadan and two others took place during Ramadan. They were scheduled at 5 p.m. and were conducted as follows: After a 10-minute warm-up either with or without listening to music, each participant performed a 5-m multiple shuttle run test, after which he was asked to answer items intended to assess his affective state during the experimental task. Results Our findings revealed that STMP was lower during Ramadan than before Ramadan in the no-music condition. Additionally, it was found that STMP was higher in the music condition than in the no-music condition during Ramadan, and that STMP measured before Ramadan did not differ from that measured during Ramadan in the music condition. Regarding affects, the findings revealed that enjoyment was lower during Ramadan than before Ramadan in the music condition, and that cognitive anxiety was lower in the music condition than in the no-music condition before Ramadan. Self-confidence was not influenced by the experimental conditions. Conclusion This study showed that listening to music during warming-up not only would be beneficial for STMP in Ramadan fasters, but also would counteract the negative effects of Ramadan observance on STMP. PMID:26301508

  8. Long non-coding RNA H19 suppresses retinoblastoma progression via counteracting miR-17-92 cluster.

    Science.gov (United States)

    Zhang, Aihui; Shang, Weiwei; Nie, Qiaoli; Li, Ting; Li, Suhui

    2018-04-01

    Long non-coding RNAs (lncRNAs) are frequently dysregulated and play important roles in many cancers. lncRNA H19 is one of the earliest discovered lncRNAs which has diverse roles in different cancers. However, the expression, roles, and action mechanisms of H19 in retinoblastoma are still largely unknown. In this study, we found that H19 is downregulated in retinoblastoma tissues and cell lines. Gain-of-function and loss-of-function assays showed that H19 inhibits retinoblastoma cell proliferation, induces retinoblastoma cell cycle arrest and cell apoptosis. Mechanistically, we identified seven miR-17-92 cluster binding sites on H19, and found that H19 directly bound to miR-17-92 cluster via these seven binding sites. Through binding to miR-17-92 cluster, H19 relieves the suppressing roles of miR-17-92 cluster on p21. Furthermore, H19 represses STAT3 activation induced by miR-17-92 cluster. Hence, our results revealed that H19 upregulates p21 expression, inhibits STAT3 phosphorylation, and downregulates the expression of STAT3 target genes BCL2, BCL2L1, and BIRC5. In addition, functional assays demonstrated that the mutation of miR-17-92 cluster binding sites on H19 abolished the proliferation inhibiting, cell cycle arrest and cell apoptosis inducing roles of H19 in retinoblastoma. In conclusion, our data suggested that H19 inhibits retinoblastoma progression via counteracting the roles of miR-17-92 cluster, and implied that enhancing the action of H19 may be a promising therapeutic strategy for retinoblastoma. © 2017 Wiley Periodicals, Inc.

  9. Galantamine counteracts development of learning impairment in guinea pigs exposed to the organophosphorus poison soman: Clinical significance

    Science.gov (United States)

    Mamczarz, Jacek; Kulkarni, Girish S.; Pereira, Edna F. R.; Albuquerque, Edson X.

    2017-01-01

    Galantamine, a drug used to treat Alzheimer’s disease, protects guinea pigs against the acute toxicity and lethality of organophosphorus (OP) compounds, including soman. Here, we tested the hypothesis that a single exposure of guinea pigs to 1xLD50 soman triggers cognitive impairments that can be counteracted by galantamine. Thus, animals were injected intramuscularly with saline (0.5 ml/kg) or galantamine (8 mg/kg) and 30 min later injected subcutaneously with soman (26.3 µg/kg) or saline. Cognitive performance was analyzed in the Morris water maze (MWM) four days or three months after the soman challenge. Fifty percent of the saline-injected animals that were challenged with soman survived with mild-to-moderate signs of acute toxicity that subsided within a few hours. These animals showed no learning impairment and no memory retention deficit, when training in the MWM started four days post-soman challenge. In contrast, animals presented significant learning impairment when testing started three months post-challenge. Though the magnitude of the impairment correlated with the severity of the acute toxicity, animals that presented no or only mild signs of toxicity were also learning impaired. All guinea pigs that were treated with galantamine survived the soman challenge with no signs of acute toxicity and learned the MWM task as control animals, regardless of when testing began. Galantamine also prevented memory extinction in both saline-and soman-challenged animals. In conclusion, learning impairment develops months after a single exposure to 1xLD50 soman, and galantamine prevents both the acute toxicity and the delayed cognitive deficits triggered by this OP poison. PMID:21784098

  10. Improvement of Antitumor Therapies Based on Vaccines and Immune-Checkpoint Inhibitors by Counteracting Tumor-Immunostimulation

    Directory of Open Access Journals (Sweden)

    Paula Chiarella

    2018-01-01

    Full Text Available Immune-checkpoint inhibitors and antitumor vaccines may produce both tumor-inhibitory and tumor-stimulatory effects on growing tumors depending on the stage of tumor growth at which treatment is initiated. These paradoxical results are not necessarily incompatible with current tumor immunology but they might better be explained assuming the involvement of the phenomenon of tumor immunostimulation. This phenomenon was originally postulated on the basis that the immune response (IR evoked in Winn tests by strong chemical murine tumors was not linear but biphasic, with strong IR producing inhibition and weak IR inducing stimulation of tumor growth. Herein, we extended those former observations to weak spontaneous murine tumors growing in pre-immunized, immune-competent and immune-depressed mice. Furthermore, we demonstrated that the interaction of specifical T cells and target tumor cells at low stimulatory ratios enhanced the production of chemokines aimed to recruit macrophages at the tumor site, which, upon activation of toll-like receptor 4 and p38 signaling pathways, would recruit and activate more macrophages and other inflammatory cells which would produce growth-stimulating signals leading to an accelerated tumor growth. On this basis, the paradoxical effects achieved by immunological therapies on growing tumors could be explained depending upon where the therapy-induced IR stands on the biphasic IR curve at each stage of tumor growth. At stages where tumor growth was enhanced (medium and large-sized tumors, counteraction of the tumor-immunostimulatory effect with anti-inflammatory strategies or, more efficiently, with selective inhibitors of p38 signaling pathways enabled the otherwise tumor-promoting immunological strategies to produce significant inhibition of tumor growth.

  11. IDH1-mutant cancer cells are sensitive to cisplatin and an IDH1-mutant inhibitor counteracts this sensitivity.

    Science.gov (United States)

    Khurshed, Mohammed; Aarnoudse, Niels; Hulsbos, Renske; Hira, Vashendriya V V; van Laarhoven, Hanneke W M; Wilmink, Johanna W; Molenaar, Remco J; van Noorden, Cornelis J F

    2018-06-07

    Isocitrate dehydrogenase ( IDH1)-1 is mutated in various types of human cancer, and the presence of this mutation is associated with improved responses to irradiation and chemotherapy in solid tumor cells. Mutated IDH1 (IDH1 MUT ) enzymes consume NADPH to produce d-2-hydroxyglutarate (d-2HG) resulting in the decreased reducing power needed for detoxification of reactive oxygen species (ROS), for example. The objective of the current study was to investigate the mechanism behind the chemosensitivity of the widely-used anticancer agent cisplatin in IDH1 MUT cancer cells. Oxidative stress, DNA damage, and mitochondrial dysfunction caused by cisplatin treatment were monitored in IDH1 MUT HCT116 colorectal cancer cells and U251 glioma cells. We found that exposure to cisplatin induced higher levels of ROS, DNA double-strand breaks (DSBs), and cell death in IDH1 MUT cancer cells, as compared with IDH1 wild-type ( IDH1 WT ) cells. Mechanistic investigations revealed that cisplatin treatment dose dependently reduced oxidative respiration in IDH1 MUT cells, which was accompanied by disturbed mitochondrial proteostasis, indicative of impaired mitochondrial activity. These effects were abolished by the IDH1 MUT inhibitor AGI-5198 and were restored by treatment with d-2HG. Thus, our study shows that altered oxidative stress responses and a vulnerable oxidative metabolism underlie the sensitivity of IDH1 MUT cancer cells to cisplatin.-Khurshed, M., Aarnoudse, N., Hulsbos, R., Hira, V. V. V., van Laarhoven, H. W. M., Wilmink, J. W., Molenaar, R. J., van Noorden, C. J. F. IDH1-mutated cancer cells are sensitive to cisplatin and an IDH1-mutant inhibitor counteracts this sensitivity.

  12. Glutamate Counteracts Dopamine/PKA Signaling via Dephosphorylation of DARPP-32 Ser-97 and Alteration of Its Cytonuclear Distribution.

    Science.gov (United States)

    Nishi, Akinori; Matamales, Miriam; Musante, Veronica; Valjent, Emmanuel; Kuroiwa, Mahomi; Kitahara, Yosuke; Rebholz, Heike; Greengard, Paul; Girault, Jean-Antoine; Nairn, Angus C

    2017-01-27

    The interaction of glutamate and dopamine in the striatum is heavily dependent on signaling pathways that converge on the regulatory protein DARPP-32. The efficacy of dopamine/D1 receptor/PKA signaling is regulated by DARPP-32 phosphorylated at Thr-34 (the PKA site), a process that inhibits protein phosphatase 1 (PP1) and potentiates PKA action. Activation of dopamine/D1 receptor/PKA signaling also leads to dephosphorylation of DARPP-32 at Ser-97 (the CK2 site), leading to localization of phospho-Thr-34 DARPP-32 in the nucleus where it also inhibits PP1. In this study the role of glutamate in the regulation of DARPP-32 phosphorylation at four major sites was further investigated. Experiments using striatal slices revealed that glutamate decreased the phosphorylation states of DARPP-32 at Ser-97 as well as Thr-34, Thr-75, and Ser-130 by activating NMDA or AMPA receptors in both direct and indirect pathway striatal neurons. The effect of glutamate in decreasing Ser-97 phosphorylation was mediated by activation of PP2A. In vitro phosphatase assays indicated that the PP2A/PR72 heterotrimer complex was likely responsible for glutamate/Ca 2+ -regulated dephosphorylation of DARPP-32 at Ser-97. As a consequence of Ser-97 dephosphorylation, glutamate induced the nuclear localization in cultured striatal neurons of dephospho-Thr-34/dephospho-Ser-97 DARPP-32. It also reduced PKA-dependent DARPP-32 signaling in slices and in vivo Taken together, the results suggest that by inducing dephosphorylation of DARPP-32 at Ser-97 and altering its cytonuclear distribution, glutamate may counteract dopamine/D1 receptor/PKA signaling at multiple cellular levels. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Glutamate Counteracts Dopamine/PKA Signaling via Dephosphorylation of DARPP-32 Ser-97 and Alteration of Its Cytonuclear Distribution*

    Science.gov (United States)

    Nishi, Akinori; Matamales, Miriam; Musante, Veronica; Valjent, Emmanuel; Kuroiwa, Mahomi; Kitahara, Yosuke; Rebholz, Heike; Greengard, Paul; Girault, Jean-Antoine; Nairn, Angus C.

    2017-01-01

    The interaction of glutamate and dopamine in the striatum is heavily dependent on signaling pathways that converge on the regulatory protein DARPP-32. The efficacy of dopamine/D1 receptor/PKA signaling is regulated by DARPP-32 phosphorylated at Thr-34 (the PKA site), a process that inhibits protein phosphatase 1 (PP1) and potentiates PKA action. Activation of dopamine/D1 receptor/PKA signaling also leads to dephosphorylation of DARPP-32 at Ser-97 (the CK2 site), leading to localization of phospho-Thr-34 DARPP-32 in the nucleus where it also inhibits PP1. In this study the role of glutamate in the regulation of DARPP-32 phosphorylation at four major sites was further investigated. Experiments using striatal slices revealed that glutamate decreased the phosphorylation states of DARPP-32 at Ser-97 as well as Thr-34, Thr-75, and Ser-130 by activating NMDA or AMPA receptors in both direct and indirect pathway striatal neurons. The effect of glutamate in decreasing Ser-97 phosphorylation was mediated by activation of PP2A. In vitro phosphatase assays indicated that the PP2A/PR72 heterotrimer complex was likely responsible for glutamate/Ca2+-regulated dephosphorylation of DARPP-32 at Ser-97. As a consequence of Ser-97 dephosphorylation, glutamate induced the nuclear localization in cultured striatal neurons of dephospho-Thr-34/dephospho-Ser-97 DARPP-32. It also reduced PKA-dependent DARPP-32 signaling in slices and in vivo. Taken together, the results suggest that by inducing dephosphorylation of DARPP-32 at Ser-97 and altering its cytonuclear distribution, glutamate may counteract dopamine/D1 receptor/PKA signaling at multiple cellular levels. PMID:27998980

  14. Effectiveness of donepezil, rivastigmine, and (+/-)huperzine A in counteracting the acute toxicity of organophosphorus nerve agents: comparison with galantamine.

    Science.gov (United States)

    Aracava, Yasco; Pereira, Edna F R; Akkerman, Miriam; Adler, Michael; Albuquerque, Edson X

    2009-12-01

    Galantamine, a centrally acting cholinesterase (ChE) inhibitor and a nicotinic allosteric potentiating ligand used to treat Alzheimer's disease, is an effective and safe antidote against poisoning with nerve agents, including soman. Here, the effectiveness of galantamine was compared with that of the centrally active ChE inhibitors donepezil, rivastigmine, and (+/-)huperzine A as a pre- and/or post-treatment to counteract the acute toxicity of soman. In the first set of experiments, male prepubertal guinea pigs were treated intramuscularly with one of the test drugs and 30 min later challenged with 1.5 x LD(50) soman (42 microg/kg s.c.). All animals that were pretreated with galantamine (6-8 mg/kg), 3 mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (+/-)huperzine A survived the soman challenge, provided that they were also post-treated with atropine (10 mg/kg i.m.). However, only galantamine was well tolerated. In subsequent experiments, the effectiveness of specific treatment regimens using 8 mg/kg galantamine, 3 mg/kg donepezil, 6 mg/kg rivastigmine, or 0.3 mg/kg (+/-)huperzine A was compared in guinea pigs challenged with soman. In the absence of atropine, only galantamine worked as an effective and safe pretreatment in animals challenged with 1.0 x LD(50) soman. Galantamine was also the only drug to afford significant protection when given to guinea pigs after 1.0 x LD(50) soman. Finally, all test drugs except galantamine reduced the survival of the animals when administered 1 or 3 h after the challenge with 0.6 or 0.7 x LD(50) soman. Thus, galantamine emerges as a superior antidotal therapy against the toxicity of soman.

  15. Icodextrin with nitroprusside increases ultrafiltration and peritoneal transport during long CAPD dwells

    NARCIS (Netherlands)

    Douma, C. E.; Hiralall, J. K.; de Waart, D. R.; Struijk, D. G.; Krediet, R. T.

    1998-01-01

    Addition of the nitric oxide (NO) donor nitroprusside to 1.36% glucose dialysate enlarges the effective peritoneal surface area during four-hour dwells. The theoretical positive effect on ultrafiltration is, however, counteracted by an increase in glucose absorption. The absorption of the glucose

  16. Dual Role of GM-CSF as a Pro-Inflammatory and a Regulatory Cytokine: Implications for Immune Therapy

    Science.gov (United States)

    Bhattacharya, Palash; Budnick, Isadore; Singh, Medha; Thiruppathi, Muthusamy; Alharshawi, Khaled; Elshabrawy, Hatem; Holterman, Mark J.

    2015-01-01

    Granulocyte macrophage colony stimulating factor (GM-CSF) is generally recognized as an inflammatory cytokine. Its inflammatory activity is primarily due its role as a growth and differentiation factor for granulocyte and macrophage populations. In this capacity, among other clinical applications, it has been used to bolster anti-tumor immune responses. GM-CSF-mediated inflammation has also been implicated in certain types of autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. Thus, agents that can block GM-CSF or its receptor have been used as anti-inflammatory therapies. However, a review of literature reveals that in many situations GM-CSF can act as an anti-inflammatory/regulatory cytokine. We and others have shown that GM-CSF can modulate dendritic cell differentiation to render them “tolerogenic,” which, in turn, can increase regulatory T-cell numbers and function. Therefore, the pro-inflammatory and regulatory effects of GM-CSF appear to depend on the dose and the presence of other relevant cytokines in the context of an immune response. A thorough understanding of the various immunomodulatory effects of GM-CSF will facilitate more appropriate use and thus further enhance its clinical utility. PMID:25803788

  17. Price increase

    CERN Multimedia

    2006-01-01

    Please take note that after five years of stable prices at Restaurant No 1 a price increase will come into force on 1st January 2006. This increase has been agreed after discussions between the CSR (Comité de Surveillance des Restaurants) and the catering company Novae and will reflect the inflation rate of the last few years. In addition, a new children's menu will be introduced, as well as 'Max Havelaar' fair-trade coffee at a price of 1.70 CHF.

  18. Price increase

    CERN Multimedia

    2005-01-01

    Please take note that after five years of stable prices at Restaurant No 1 a price increase will come into force on 1st January 2006. This increase has been agreed after discussions between the CSR (Comité de Surveillance des Restaurants) and the catering company Novae and will reflect the inflation rate of the last few years. In addition, a new children's menu will be introduced as well as 'Max Havelaar' fair-trade coffee at a price of 1.70 CHF.

  19. Anthocyanins and phenolic acids from a wild blueberry (Vaccinium angustifolium) powder counteract lipid accumulation in THP-1-derived macrophages

    DEFF Research Database (Denmark)

    Del Bo', Cristian; Cao, Yi; Roursgaard, Martin

    2016-01-01

    PURPOSE: Blueberries are a rich source of anthocyanins (ACNs) and phenolic acids (PA), which are hypothesized to protect against development of atherosclerosis. The present study examined the effect of an ACN- and PA-rich fractions, obtained from a wild blueberry powder, on the capacity...... to counteract lipid accumulation in macrophages derived from monocytic THP-1 cells. In addition, we tested the capacity of pure ACNs and their metabolites to alter lipid accumulation. METHODS: THP-1-derived macrophages were incubated with fatty acids (500 μM oleic/palmitic acid, 2:1 ratio) and different...... concentrations (from 0.05 to 10 μg mL(-1)) of ACN- and PA-rich fractions, pure ACN standards (malvidin, delphinidin and cyanidin 3-glucoside), and metabolites (syringic, gallic and protocatechuic acids). Lipid accumulation was quantified with the fluorescent dye Nile red. RESULTS: Lipid accumulation was reduced...

  20. Deciphering complex dynamics of water counteraction around secondary structural elements of allosteric protein complex: Case study of SAP-SLAM system in signal transduction cascade.

    Science.gov (United States)

    Samanta, Sudipta; Mukherjee, Sanchita

    2018-01-28

    The first hydration shell of a protein exhibits heterogeneous behavior owing to several attributes, majorly local polarity and structural flexibility as revealed by solvation dynamics of secondary structural elements. We attempt to recognize the change in complex water counteraction generated due to substantial alteration in flexibility during protein complex formation. The investigation is carried out with the signaling lymphocytic activation molecule (SLAM) family of receptors, expressed by an array of immune cells, and interacting with SLAM-associated protein (SAP), composed of one SH2 domain. All atom molecular dynamics simulations are employed to the aqueous solutions of free SAP and SLAM-peptide bound SAP. We observed that water dynamics around different secondary structural elements became highly affected as well as nicely correlated with the SLAM-peptide induced change in structural rigidity obtained by thermodynamic quantification. A few instances of contradictory dynamic features of water to the change in structural flexibility are explained by means of occluded polar residues by the peptide. For βD, EFloop, and BGloop, both structural flexibility and solvent accessibility of the residues confirm the obvious contribution. Most importantly, we have quantified enhanced restriction in water dynamics around the second Fyn-binding site of the SAP due to SAP-SLAM complexation, even prior to the presence of Fyn. This observation leads to a novel argument that SLAM induced more restricted water molecules could offer more water entropic contribution during the subsequent Fyn binding and provide enhanced stability to the SAP-Fyn complex in the signaling cascade. Finally, SLAM induced water counteraction around the second binding site of the SAP sheds light on the allosteric property of the SAP, which becomes an integral part of the underlying signal transduction mechanism.

  1. Life-long environmental enrichment counteracts spatial learning, reference and working memory deficits in middle-aged rats subjected to perinatal asphyxia.

    Science.gov (United States)

    Galeano, Pablo; Blanco, Eduardo; Logica Tornatore, Tamara M A; Romero, Juan I; Holubiec, Mariana I; Rodríguez de Fonseca, Fernando; Capani, Francisco

    2014-01-01

    Continuous environmental stimulation induced by exposure to enriched environment (EE) has yielded cognitive benefits in different models of brain injury. Perinatal asphyxia results from a lack of oxygen supply to the fetus and is associated with long-lasting neurological deficits. However, the effects of EE in middle-aged rats suffering perinatal asphyxia are unknown. Therefore, the aim of the present study was to assess whether life-long exposure to EE could counteract the cognitive and behavioral alterations in middle-aged asphyctic rats. Experimental groups consisted of rats born vaginally (CTL), by cesarean section (C+), or by C+ following 19 min of asphyxia at birth (PA). At weaning, rats were assigned to standard (SE) or enriched environment (EE) for 18 months. During the last month of housing, animals were submitted to a behavioral test battery including Elevated Plus Maze, Open Field, Novel Object Recognition and Morris water maze (MWM). Results showed that middle-aged asphyctic rats, reared in SE, exhibited an impaired performance in the spatial reference and working memory versions of the MWM. EE was able to counteract these cognitive impairments. Moreover, EE improved the spatial learning performance of middle-aged CTL and C+ rats. On the other hand, all groups reared in SE did not differ in locomotor activity and anxiety levels, while EE reduced locomotion and anxiety, regardless of birth condition. Recognition memory was altered neither by birth condition nor by housing environment. These results support the importance of environmental stimulation across the lifespan to prevent cognitive deficits induced by perinatal asphyxia.

  2. The LOV protein of Xanthomonas citri subsp. citri plays a significant role in the counteraction of plant immune responses during citrus canker.

    Directory of Open Access Journals (Sweden)

    Ivana Kraiselburd

    Full Text Available Pathogens interaction with a host plant starts a set of immune responses that result in complex changes in gene expression and plant physiology. Light is an important modulator of plant defense response and recent studies have evidenced the novel influence of this environmental stimulus in the virulence of several bacterial pathogens. Xanthomonas citri subsp. citri is the bacterium responsible for citrus canker disease, which affects most citrus cultivars. The ability of this bacterium to colonize host plants is influenced by bacterial blue-light sensing through a LOV-domain protein and disease symptoms are considerably altered upon deletion of this protein. In this work we aimed to unravel the role of this photoreceptor during the bacterial counteraction of plant immune responses leading to citrus canker development. We performed a transcriptomic analysis in Citrus sinensis leaves inoculated with the wild type X. citri subsp. citri and with a mutant strain lacking the LOV protein by a cDNA microarray and evaluated the differentially regulated genes corresponding to specific biological processes. A down-regulation of photosynthesis-related genes (together with a corresponding decrease in photosynthesis rates was observed upon bacterial infection, this effect being more pronounced in plants infected with the lov-mutant bacterial strain. Infection with this strain was also accompanied with the up-regulation of several secondary metabolism- and defense response-related genes. Moreover, we found that relevant plant physiological alterations triggered by pathogen attack such as cell wall fortification and tissue disruption were amplified during the lov-mutant strain infection. These results suggest the participation of the LOV-domain protein from X. citri subsp. citri in the bacterial counteraction of host plant defense response, contributing in this way to disease development.

  3. The LOV Protein of Xanthomonas citri subsp. citri Plays a Significant Role in the Counteraction of Plant Immune Responses during Citrus Canker

    Science.gov (United States)

    Kraiselburd, Ivana; Daurelio, Lucas D.; Tondo, María Laura; Merelo, Paz; Cortadi, Adriana A.; Talón, Manuel; Tadeo, Francisco R.; Orellano, Elena G.

    2013-01-01

    Pathogens interaction with a host plant starts a set of immune responses that result in complex changes in gene expression and plant physiology. Light is an important modulator of plant defense response and recent studies have evidenced the novel influence of this environmental stimulus in the virulence of several bacterial pathogens. Xanthomonas citri subsp. citri is the bacterium responsible for citrus canker disease, which affects most citrus cultivars. The ability of this bacterium to colonize host plants is influenced by bacterial blue-light sensing through a LOV-domain protein and disease symptoms are considerably altered upon deletion of this protein. In this work we aimed to unravel the role of this photoreceptor during the bacterial counteraction of plant immune responses leading to citrus canker development. We performed a transcriptomic analysis in Citrus sinensis leaves inoculated with the wild type X. citri subsp. citri and with a mutant strain lacking the LOV protein by a cDNA microarray and evaluated the differentially regulated genes corresponding to specific biological processes. A down-regulation of photosynthesis-related genes (together with a corresponding decrease in photosynthesis rates) was observed upon bacterial infection, this effect being more pronounced in plants infected with the lov-mutant bacterial strain. Infection with this strain was also accompanied with the up-regulation of several secondary metabolism- and defense response-related genes. Moreover, we found that relevant plant physiological alterations triggered by pathogen attack such as cell wall fortification and tissue disruption were amplified during the lov-mutant strain infection. These results suggest the participation of the LOV-domain protein from X. citri subsp. citri in the bacterial counteraction of host plant defense response, contributing in this way to disease development. PMID:24260514

  4. JIL-1 and Su(var)3-7 Interact Genetically and Counteract Each Other's Effect on Position-Effect Variegation in Drosophila

    Science.gov (United States)

    Deng, Huai; Cai, Weili; Wang, Chao; Lerach, Stephanie; Delattre, Marion; Girton, Jack; Johansen, Jørgen; Johansen, Kristen M.

    2010-01-01

    The essential JIL-1 histone H3S10 kinase is a key regulator of chromatin structure that functions to maintain euchromatic domains while counteracting heterochromatization and gene silencing. In the absence of the JIL-1 kinase, two of the major heterochromatin markers H3K9me2 and HP1a spread in tandem to ectopic locations on the chromosome arms. Here we address the role of the third major heterochromatin component, the zinc-finger protein Su(var)3-7. We show that the lethality but not the chromosome morphology defects associated with the null JIL-1 phenotype to a large degree can be rescued by reducing the dose of the Su(var)3-7 gene and that Su(var)3-7 and JIL-1 loss-of-function mutations have an antagonistic and counterbalancing effect on position-effect variegation (PEV). Furthermore, we show that in the absence of JIL-1 kinase activity, Su(var)3-7 gets redistributed and upregulated on the chromosome arms. Reducing the dose of the Su(var)3-7 gene dramatically decreases this redistribution; however, the spreading of H3K9me2 to the chromosome arms was unaffected, strongly indicating that ectopic Su(var)3-9 activity is not a direct cause of lethality. These observations suggest a model where Su(var)3-7 functions as an effector downstream of Su(var)3-9 and H3K9 dimethylation in heterochromatic spreading and gene silencing that is normally counteracted by JIL-1 kinase activity. PMID:20457875

  5. Deciphering complex dynamics of water counteraction around secondary structural elements of allosteric protein complex: Case study of SAP-SLAM system in signal transduction cascade

    Science.gov (United States)

    Samanta, Sudipta; Mukherjee, Sanchita

    2018-01-01

    The first hydration shell of a protein exhibits heterogeneous behavior owing to several attributes, majorly local polarity and structural flexibility as revealed by solvation dynamics of secondary structural elements. We attempt to recognize the change in complex water counteraction generated due to substantial alteration in flexibility during protein complex formation. The investigation is carried out with the signaling lymphocytic activation molecule (SLAM) family of receptors, expressed by an array of immune cells, and interacting with SLAM-associated protein (SAP), composed of one SH2 domain. All atom molecular dynamics simulations are employed to the aqueous solutions of free SAP and SLAM-peptide bound SAP. We observed that water dynamics around different secondary structural elements became highly affected as well as nicely correlated with the SLAM-peptide induced change in structural rigidity obtained by thermodynamic quantification. A few instances of contradictory dynamic features of water to the change in structural flexibility are explained by means of occluded polar residues by the peptide. For βD, EFloop, and BGloop, both structural flexibility and solvent accessibility of the residues confirm the obvious contribution. Most importantly, we have quantified enhanced restriction in water dynamics around the second Fyn-binding site of the SAP due to SAP-SLAM complexation, even prior to the presence of Fyn. This observation leads to a novel argument that SLAM induced more restricted water molecules could offer more water entropic contribution during the subsequent Fyn binding and provide enhanced stability to the SAP-Fyn complex in the signaling cascade. Finally, SLAM induced water counteraction around the second binding site of the SAP sheds light on the allosteric property of the SAP, which becomes an integral part of the underlying signal transduction mechanism.

  6. The counteracting effects of elevated atmospheric CO2 concentrations and drought episodes: Studies of enchytraeid communities in a dry heathland

    DEFF Research Database (Denmark)

    Maraldo, Kristine; Krogh, Paul Henning; Linden, Leon

    2010-01-01

    The potential impacts of interactions of multiple climate change factors in soil ecosystems have received little attention. Most studies have addressed effects of single factors such as increased temperature or atmospheric CO2 but little is known about how such environmental factors will interact...... impact of drought on the enchytraeids, compared to the year with a wet summer and autumn (2007). Our study emphasises the importance of multi-factorial experimental design as a means to investigate effects of climatic changes.......The potential impacts of interactions of multiple climate change factors in soil ecosystems have received little attention. Most studies have addressed effects of single factors such as increased temperature or atmospheric CO2 but little is known about how such environmental factors will interact....... In the present study we investigate the effects of in situ exposure to elevated atmospheric CO2 concentration, increased temperatures and prolonged drought episodes on field communities of Enchytraeidae (Oligochaeta) in a dry heathland (Brandbjerg, Denmark). Increased CO2 had a positive effect on enchytraeid...

  7. Interleukin-6 counteracts therapy-induced cellular oxidative stress in multiple myeloma by up-regulating manganese superoxide dismutase.

    Science.gov (United States)

    Brown, Charles O; Salem, Kelley; Wagner, Brett A; Bera, Soumen; Singh, Neeraj; Tiwari, Ajit; Choudhury, Amit; Buettner, Garry R; Goel, Apollina

    2012-06-15

    IL (interleukin)-6, an established growth factor for multiple myeloma cells, induces myeloma therapy resistance, but the resistance mechanisms remain unclear. The present study determines the role of IL-6 in re-establishing intracellular redox homoeostasis in the context of myeloma therapy. IL-6 treatment increased myeloma cell resistance to agents that induce oxidative stress, including IR (ionizing radiation) and Dex (dexamethasone). Relative to IR alone, myeloma cells treated with IL-6 plus IR demonstrated reduced annexin/propidium iodide staining, caspase 3 activation, PARP [poly(ADP-ribose) polymerase] cleavage and mitochondrial membrane depolarization with increased clonogenic survival. IL-6 combined with IR or Dex increased early intracellular pro-oxidant levels that were causally related to activation of NF-κB (nuclear factor κB) as determined by the ability of N-acetylcysteine to suppress both pro-oxidant levels and NF-κB activation. In myeloma cells, upon combination with hydrogen peroxide treatment, relative to TNF (tumour necrosis factor)-α, IL-6 induced an early perturbation in reduced glutathione level and increased NF-κB-dependent MnSOD (manganese superoxide dismutase) expression. Furthermore, knockdown of MnSOD suppressed the IL-6-induced myeloma cell resistance to radiation. MitoSOX Red staining showed that IL-6 treatment attenuated late mitochondrial oxidant production in irradiated myeloma cells. The present study provides evidence that increases in MnSOD expression mediate IL-6-induced resistance to Dex and radiation in myeloma cells. The results of the present study indicate that inhibition of antioxidant pathways could enhance myeloma cell responses to radiotherapy and/or chemotherapy.

  8. Interleukin-6 counteracts therapy-induced cellular oxidative stress in multiple myeloma by up-regulating manganese superoxide dismutase

    OpenAIRE

    Brown, Charles O.; Salem, Kelley; Wagner, Brett A.; Bera, Soumen; Singh, Neeraj; Tiwari, Ajit; Choudhury, Amit; Buettner, Garry R.; Goel, Apollina

    2012-01-01

    IL (interleukin)-6, an established growth factor for multiple myeloma cells, induces myeloma therapy resistance, but the resistance mechanisms remain unclear. The present study determines the role of IL-6 in re-establishing intracellular redox homoeostasis in the context of myeloma therapy. IL-6 treatment increased myeloma cell resistance to agents that induce oxidative stress, including IR (ionizing radiation) and Dex (dexamethasone). Relative to IR alone, myeloma cells treated with IL-6 plu...

  9. Caloric restriction counteracts age-related changes in the activities of sorbitol metabolizing enzymes from mouse liver

    Science.gov (United States)

    Hagopian, Kevork; Ramsey, Jon J.; Weindruch, Richard

    2009-01-01

    The influence of caloric restriction (CR) on hepatic sorbitol-metabolizing enzyme activities was investigated in young and old mice. Aldose reductase and sorbitol dehydrogenase activities were significantly lower in old CR mice than in old controls. Young CR mice showed decreased aldose reductase activity and a trend towards decreased sorbitol dehydrogenase when compared to controls. Metabolites of the pathway, namely sorbitol, glucose and fructose were decreased by CR in young and old mice. Pyruvate levels were decreased by CR in both young and old mice, while lactate decreased only in old CR. Malate levels increased in old CR but remained unchanged in young CR, when compared with controls. Accordingly, the lactae/pyruvate and malate/pyruvate ratios in young and old CR mice were increased, indicating increased NADH/NAD and NADPH/NADP redox couples, respectively. The results indicate that decreased glucose levels under CR conditions lead to decreased sorbitol pathway enzyme activities and metabolite levels, and could contribute to the beneficial effects of long-term CR through decreased sorbitol levels and NADPH sparing. PMID:18953666

  10. A Red Blood Cell Membrane-Camouflaged Nanoparticle Counteracts Streptolysin O-Mediated Virulence Phenotypes of Invasive Group A Streptococcus

    Directory of Open Access Journals (Sweden)

    Tamara Escajadillo

    2017-07-01

    Full Text Available Group A Streptococcus (GAS, an important human-specific Gram-positive bacterial pathogen, is associated with a broad spectrum of disease, ranging from mild superficial infections such as pharyngitis and impetigo, to serious invasive infections including necrotizing fasciitis and streptococcal toxic shock syndrome. The GAS pore-forming streptolysin O (SLO is a well characterized virulence factor produced by nearly all GAS clinical isolates. High level expression of SLO is epidemiologically linked to intercontinental dissemination of hypervirulent clonotypes and poor clinical outcomes. SLO can trigger macrophage and neutrophil cell death and/or the inactivation of immune cell functions, and promotes tissue injury and bacterial survival in animal models of infection. In the present work, we describe how the pharmacological presentation of red blood cell (RBC derived biomimetic nanoparticles (“nanosponges” can sequester SLO and block the ability of GAS to damage host cells, thereby preserving innate immune function and increasing bacterial clearance in vitro and in vivo. Nanosponge administration protected human neutrophils, macrophages, and keratinocytes against SLO-mediated cytotoxicity. This therapeutic intervention prevented SLO-induced macrophage apoptosis and increased neutrophil extracellular trap formation, allowing increased GAS killing by the respective phagocytic cell types. In a murine model of GAS necrotizing skin infection, local administration of the biomimetic nanosponges was associated with decreased lesion size and reduced bacterial colony-forming unit recovery. Utilization of a toxin decoy and capture platform that inactivates the secreted SLO before it contacts the host cell membrane, presents a novel virulence factor targeted strategy that could be a powerful adjunctive therapy in severe GAS infections where morbidity and mortality are high despite antibiotic treatment.

  11. Positive relationship between dietary fat, ethanol intake, triglycerides, and hypothalamic peptides: counteraction by lipid-lowering drugs.

    Science.gov (United States)

    Barson, Jessica R; Karatayev, Olga; Chang, Guo-Qing; Johnson, Deanne F; Bocarsly, Miriam E; Hoebel, Bartley G; Leibowitz, Sarah F

    2009-09-01

    Studies in both humans and animals suggest a positive relationship between the intake of ethanol and intake of fat, which may contribute to alcohol abuse. This relationship may be mediated, in part, by hypothalamic orexigenic peptides such as orexin (OX), which stimulate both consumption of ethanol and fat, and circulating triglycerides (TGs), which stimulate these peptides and promote consummatory behavior. The present study investigated this vicious cycle between ethanol and fat, to further characterize its relation to TGs and to test the effects of lowering TG levels. In Experiment 1, the behavioral relationship between fat intake and ethanol was confirmed. Adult male Sprague-Dawley rats, chronically injected intraperitoneally with ethanol (1g/kg) and tested in terms of their preference for a high-fat diet (HFD) compared with low-fat diet (LFD), showed a significant increase in their fat preference, compared with rats injected with saline, in measures of 2h and 24h intake. Experiment 2 tested the relationship of circulating TGs in this positive association between ethanol and fat, in rats chronically consuming 9% ethanol versus water and given acute meal tests (25kcal) of a HFD versus LFD. Levels of TGs were elevated in response to both chronic drinking of ethanol versus water and acute eating of a high-fat versus low-fat meal. Most importantly, ethanol and a HFD showed an interaction effect, whereby their combination produced a considerably larger increase in TG levels (+172%) compared to ethanol with a LFD (+111%). In Experiment 3, a direct manipulation of TG levels was found to affect ethanol intake. After intragastric administration of gemfibrozil (50mg/kg) compared with vehicle, TG levels were lowered by 37%, and ethanol intake was significantly reduced. In Experiment 4, the TG-lowering drug gemfibrozil also caused a significant reduction in the expression of the orexigenic peptide, OX, in the perifornical lateral hypothalamus. These results support the

  12. Dihydroartemisinin counteracts fibrotic portal hypertension via farnesoid X receptor-dependent inhibition of hepatic stellate cell contraction.

    Science.gov (United States)

    Xu, Wenxuan; Lu, Chunfeng; Zhang, Feng; Shao, Jiangjuan; Yao, Shunyu; Zheng, Shizhong

    2017-01-01

    Portal hypertension is a frequent pathological symptom occurring especially in hepatic fibrosis and cirrhosis. Current paradigms indicate that inhibition of hepatic stellate cell (HSC) activation and contraction is anticipated to be an attractive therapeutic strategy, because activated HSC dominantly facilitates an increase in intrahepatic vein pressure through secreting extracellular matrix and contracting. Our previous in vitro study indicated that dihydroartemisinin (DHA) inhibited contractility of cultured HSC by activating intracellular farnesoid X receptor (FXR). However, the effect of DHA on fibrosis-related portal hypertension still requires clarification. In this study, gain- and loss-of-function models of FXR in HSC were established to investigate the mechanisms underlying DHA protection against chronic CCl 4 -caused hepatic fibrosis and portal hypertension. Immunofluorescence staining visually showed a decrease in FXR expression in CCl 4 -administrated rat HSC but an increase in that in DHA-treated rat HSC. Serum diagnostics and morphological analyses consistently indicated that DHA exhibited hepatoprotective effects on CCl 4 -induced liver injury. DHA also reduced CCl 4 -caused inflammatory mediator expression and inflammatory cell infiltration. These improvements were further enhanced by INT-747 but weakened by Z-guggulsterone. Noteworthily, DHA, analogous to INT-747, significantly lowered portal vein pressure and suppressed fibrogenesis. Experiments on mice using FXR shRNA lentivirus consolidated the results above. Mechanistically, inhibition of HSC activation and contraction was found as a cellular basis for DHA to relieve portal hypertension. These findings demonstrated that DHA attenuated portal hypertension in fibrotic rodents possibly by targeting HSC contraction via a FXR activation-dependent mechanism. FXR could be a target molecule for reducing portal hypertension during hepatic fibrosis. © 2016 Federation of European Biochemical Societies.

  13. In Vivo Study on the Pharmacological Interactions between a Chinese Herbal Formula ELP and Antiresorptive Drugs to Counteract Osteoporosis

    Directory of Open Access Journals (Sweden)

    Chun-Hay Ko

    2012-01-01

    Full Text Available Antiresorptive drugs, alendronate and raloxifene, are effective in lowering bone mineral density (BMD loss in postmenopausal women. However, long-term treatment may be associated with serious side effects. Our research group has recently discovered that a Chinese herbal formula, ELP, could significantly reduce BMD loss in animal and human studies. Therefore, the present study aimed to investigate the potential synergistic bone-protective effects of different herb-drug combinations using ovariectomized rats. To assess the efficacy of different combinations, the total BMD was monitored biweekly in the 8-week course of daily oral treatment. Bone microarchitecture, bone strength, and deoxypyridinoline level were also determined after 8 weeks. From our results, coadministration of ELP and raloxifene increased the total tibial BMD by 5.26% (2.5 mg/kg/day of raloxifene; P=0.014 and 5.94% (0.25 mg/kg/day of raloxifene; P=0.026 when compared with the respective dosage groups with raloxifene alone. Similar synergistic effects were also observed in BMD increase at distal femur (0.25 mg/kg/day; P=0.001 and reduction in urinary deoxypyridinoline crosslink excretion (2.5 and 0.25 mg/kg/day; both P=0.02. However, such interactions could not be observed in all alendronate-treated groups. Our data provide first evidence that ELP could synergistically enhance the therapeutic effects of raloxifene, so that the clinical dosage of raloxifene could be reduced.

  14. N-acetylcysteine Counteracts Adipose Tissue Macrophage Infiltration and Insulin Resistance Elicited by Advanced Glycated Albumin in Healthy Rats

    Directory of Open Access Journals (Sweden)

    Karolline S. da Silva

    2017-09-01

    Full Text Available Background: Advanced glycation endproducts elicit inflammation. However, their role in adipocyte macrophage infiltration and in the development of insulin resistance, especially in the absence of the deleterious biochemical pathways that coexist in diabetes mellitus, remains unknown. We investigated the effect of chronic administration of advanced glycated albumin (AGE-albumin in healthy rats, associated or not with N-acetylcysteine (NAC treatment, on insulin sensitivity, adipose tissue transcriptome and macrophage infiltration and polarization.Methods: Male Wistar rats were intraperitoneally injected with control (C or AGE-albumin alone, or, together with NAC in the drinking water. Biochemical parameters, lipid peroxidation, gene expression and protein contents were, respectively, determined by enzymatic techniques, reactive thiobarbituric acid substances, RT-qPCR and immunohistochemistry or immunoblot. Carboxymethyllysine (CML and pyrraline (PYR were determined by LC/mass spectrometry (LC-MS/MS and ELISA.Results: CML and PYR were higher in AGE-albumin as compared to C. Food consumption, body weight, systolic blood pressure, plasma lipids, glucose, hepatic and renal function, adipose tissue relative weight and adipocyte number were similar among groups. In AGE-treated animals, insulin resistance, adipose macrophage infiltration and Col12a1 mRNA were increased with no changes in M1 and M2 phenotypes as compared to C-albumin-treated rats. Total GLUT4 content was reduced by AGE-albumin as compared to C-albumin. NAC improved insulin sensitivity, reduced urine TBARS, adipose macrophage number and Itgam and Mrc mRNA and increased Slc2a4 and Ppara. CD11b, CD206, Ager, Ddost, Cd36, Nfkb1, Il6, Tnf, Adipoq, Retn, Arg, and Il12 expressions were similar among groups.Conclusions: AGE-albumin sensitizes adipose tissue to inflammation due to macrophage infiltration and reduces GLUT4, contributing to insulin resistance in healthy rats. NAC antagonizes AGE

  15. PGC-1/Spargel Counteracts High-Fat-Diet-Induced Obesity and Cardiac Lipotoxicity Downstream of TOR and Brummer ATGL Lipase

    Directory of Open Access Journals (Sweden)

    Soda Balla Diop

    2015-03-01

    Full Text Available Obesity and metabolic syndrome are associated with an increased risk for lipotoxic cardiomyopathy, which is strongly correlated with excessive accumulation of lipids in the heart. Obesity- and type-2-diabetes-related disorders have been linked to altered expression of the transcriptional cofactor PGC-1α, which regulates the expression of genes involved in energy metabolism. Using Drosophila, we identify PGC-1/spargel (PGC-1/srl as a key antagonist of high-fat diet (HFD-induced lipotoxic cardiomyopathy. We find that HFD-induced lipid accumulation and cardiac dysfunction are mimicked by reduced PGC-1/srl function and reversed by PGC-1/srl overexpression. Moreover, HFD feeding lowers PGC-1/srl expression by elevating TOR signaling and inhibiting expression of the Drosophila adipocyte triglyceride lipase (ATGL (Brummer, both of which function as upstream modulators of PGC-1/srl. The lipogenic transcription factor SREBP also contributes to HFD-induced cardiac lipotoxicity, likely in parallel with PGC-1/srl. These results suggest a regulatory network of key metabolic genes that modulates lipotoxic heart dysfunction.

  16. Meaning Of The Term "Corruption Offense" As A Feature Of The Public Prosecutor's Supervision Over The Legislation On The Corruption Counteraction In The Municipal Governments Execution

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    Kseniya D. Okuneva

    2014-12-01

    Full Text Available In the present article theoretical and practical aspects of the corruption offense definition, which are being characteristic features of the methodology of prosecutorial supervision over the legislation on counteraction to corruption in local government are analyzed. Federal Law of Jan. 17, 1992 No. 2202-1 "On the Procuracy of the Russian Federation" (Article 21 establishes the public prosecutor's supervision over the legislation on combating corruption in local government execution, which is a special sub-cluster. On general terms of theoretical techniques of the prosecutor's supervision, taking into account its specific and complex nature of corruption prosecutors based activities in this area. Author emphasizes attention on characteristics of the corruption offense, as well as aspects of legal responsibility, which lie in the fact that it is applied in accordance with law to offender as measures of state coercion of personal, financial or organizational nature for the offense committed; responsibilities of the person, who committed the offense, to be subject to measures of state coercion. In the conclusion author notes that specifics of corruption offenses that are subject of prosecutorial supervision over the execution of legislation on combating corruption in local government is determined by the special status of the offense subjects, as well as the content of legal prohibitions and legal responsibilities in the field of ​​anti-corruption at the municipal level.

  17. Chemotherapeutic-Induced Cardiovascular Dysfunction: Physiological Effects, Early Detection—The Role of Telomerase to Counteract Mitochondrial Defects and Oxidative Stress

    Science.gov (United States)

    Quryshi, Nabeel; Norwood Toro, Laura E.; Ait-Aissa, Karima; Kong, Amanda; Beyer, Andreas M.

    2018-01-01

    Although chemotherapeutics can be highly effective at targeting malignancies, their ability to trigger cardiovascular morbidity is clinically significant. Chemotherapy can adversely affect cardiovascular physiology, resulting in the development of cardiomyopathy, heart failure and microvascular defects. Specifically, anthracyclines are known to cause an excessive buildup of free radical species and mitochondrial DNA damage (mtDNA) that can lead to oxidative stress-induced cardiovascular apoptosis. Therefore, oncologists and cardiologists maintain a network of communication when dealing with patients during treatment in order to treat and prevent chemotherapy-induced cardiovascular damage; however, there is a need to discover more accurate biomarkers and therapeutics to combat and predict the onset of cardiovascular side effects. Telomerase, originally discovered to promote cellular proliferation, has recently emerged as a potential mechanism to counteract mitochondrial defects and restore healthy mitochondrial vascular phenotypes. This review details mechanisms currently used to assess cardiovascular damage, such as C-reactive protein (CRP) and troponin levels, while also unearthing recently researched biomarkers, including circulating mtDNA, telomere length and telomerase activity. Further, we explore a potential role of telomerase in the mitigation of mitochondrial reactive oxygen species and maintenance of mtDNA integrity. Telomerase activity presents a promising indicator for the early detection and treatment of chemotherapy-derived cardiac damage. PMID:29534446

  18. Juvenile hormone counteracts the bHLH-PAS transcription factors MET and GCE to prevent caspase-dependent programmed cell death in Drosophila.

    Science.gov (United States)

    Liu, Ying; Sheng, Zhentao; Liu, Hanhan; Wen, Di; He, Qianyu; Wang, Sheng; Shao, Wei; Jiang, Rong-Jing; An, Shiheng; Sun, Yaning; Bendena, William G; Wang, Jian; Gilbert, Lawrence I; Wilson, Thomas G; Song, Qisheng; Li, Sheng

    2009-06-01

    Juvenile hormone (JH) regulates many developmental and physiological events in insects, but its molecular mechanism remains conjectural. Here we report that genetic ablation of the corpus allatum cells of the Drosophila ring gland (the JH source) resulted in JH deficiency, pupal lethality and precocious and enhanced programmed cell death (PCD) of the larval fat body. In the fat body of the JH-deficient animals, Dronc and Drice, two caspase genes that are crucial for PCD induced by the molting hormone 20-hydroxyecdysone (20E), were significantly upregulated. These results demonstrated that JH antagonizes 20E-induced PCD by restricting the mRNA levels of Dronc and Drice. The antagonizing effect of JH on 20E-induced PCD in the fat body was further confirmed in the JH-deficient animals by 20E treatment and RNA interference of the 20E receptor EcR. Moreover, MET and GCE, the bHLH-PAS transcription factors involved in JH action, were shown to induce PCD by upregulating Dronc and Drice. In the Met- and gce-deficient animals, Dronc and Drice were downregulated, whereas in the Met-overexpression fat body, Dronc and Drice were significantly upregulated leading to precocious and enhanced PCD, and this upregulation could be suppressed by application of the JH agonist methoprene. For the first time, we demonstrate that JH counteracts MET and GCE to prevent caspase-dependent PCD in controlling fat body remodeling and larval-pupal metamorphosis in Drosophila.

  19. PRC2 inhibition counteracts the culture-associated loss of engraftment potential of human cord blood-derived hematopoietic stem and progenitor cells.

    Science.gov (United States)

    Varagnolo, Linda; Lin, Qiong; Obier, Nadine; Plass, Christoph; Dietl, Johannes; Zenke, Martin; Claus, Rainer; Müller, Albrecht M

    2015-07-22

    Cord blood hematopoietic stem cells (CB-HSCs) are an outstanding source for transplantation approaches. However, the amount of cells per donor is limited and culture expansion of CB-HSCs is accompanied by a loss of engraftment potential. In order to analyze the molecular mechanisms leading to this impaired potential we profiled global and local epigenotypes during the expansion of human CB hematopoietic stem and progenitor cells (HPSCs). Human CB-derived CD34+ cells were cultured in serum-free medium together with SCF, TPO, FGF, with or without Igfbp2 and Angptl5 (STF/STFIA cocktails). As compared to the STF cocktail, the STFIA cocktail maintains in vivo repopulation capacity of cultured CD34+ cells. Upon expansion, CD34+ cells genome-wide remodel their epigenotype and depending on the cytokine cocktail, cells show different H3K4me3 and H3K27me3 levels. Expanding cells without Igfbp2 and Angptl5 leads to higher global H3K27me3 levels. ChIPseq analyses reveal a cytokine cocktail-dependent redistribution of H3K27me3 profiles. Inhibition of the PRC2 component EZH2 counteracts the culture-associated loss of NOD scid gamma (NSG) engraftment potential. Collectively, our data reveal chromatin dynamics that underlie the culture-associated loss of engraftment potential. We identify PRC2 component EZH2 as being involved in the loss of engraftment potential during the in vitro expansion of HPSCs.

  20. Molecular and functional interactions of cat APOBEC3 and feline foamy and immunodeficiency virus proteins: different ways to counteract host-encoded restriction.

    Science.gov (United States)

    Chareza, Sarah; Slavkovic Lukic, Dragana; Liu, Yang; Räthe, Ann-Mareen; Münk, Carsten; Zabogli, Elisa; Pistello, Mauro; Löchelt, Martin

    2012-03-15

    Defined host-encoded feline APOBEC3 (feA3) cytidine deaminases efficiently restrict the replication and spread of exogenous retroviruses like Feline Immunodeficiency Virus (FIV) and Feline Foamy Virus (FFV) which developed different feA3 counter-acting strategies. Here we characterize the molecular interaction of FFV proteins with the diverse feA3 proteins. The FFV accessory protein Bet is the virus-encoded defense factor which is shown here to bind all feA3 proteins independent of whether they restrict FFV, a feature shared with FIV Vif that induces degradation of all feA3s including those that do not inactivate FIV. In contrast, only some feA3 proteins bind to FFV Gag, a pattern that in part reflects the restriction pattern detected. Additionally, one-domain feA3 proteins can homo- and hetero-dimerize in vitro, but a trans-dominant phenotype of any of the low-activity feA3 forms on FFV restriction by one of the highly-active feA3Z2 proteins was not detectable. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Escherichia coli α-hemolysin counteracts the anti-virulence innate immune response triggered by the Rho GTPase activating toxin CNF1 during bacteremia.

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    Mamady Diabate

    2015-03-01

    Full Text Available The detection of the activities of pathogen-encoded virulence factors by the innate immune system has emerged as a new paradigm of pathogen recognition. Much remains to be determined with regard to the molecular and cellular components contributing to this defense mechanism in mammals and importance during infection. Here, we reveal the central role of the IL-1β signaling axis and Gr1+ cells in controlling the Escherichia coli burden in the blood in response to the sensing of the Rho GTPase-activating toxin CNF1. Consistently, this innate immune response is abrogated in caspase-1/11-impaired mice or following the treatment of infected mice with an IL-1β antagonist. In vitro experiments further revealed the synergistic effects of CNF1 and LPS in promoting the maturation/secretion of IL-1β and establishing the roles of Rac, ASC and caspase-1 in this pathway. Furthermore, we found that the α-hemolysin toxin inhibits IL-1β secretion without affecting the recruitment of Gr1+ cells. Here, we report the first example of anti-virulence-triggered immunity counteracted by a pore-forming toxin during bacteremia.

  2. Cowpea mosaic virus RNA-1 acts as an amplicon whose effects can be counteracted by a RNA-2-encoded suppressor of silencing

    International Nuclear Information System (INIS)

    Liu Li; Grainger, Jef; Canizares, M. Carmen; Angell, Susan M.; Lomonossoff, George P.

    2004-01-01

    Lines of Nicotiana benthamiana transgenic for full-length copies of both Cowpea mosaic virus (CPMV) genomic RNAs, either singly or together, have been produced. Plants transgenic for both RNAs developed symptoms characteristic of a CPMV infection. When plants transgenic for RNA-1 were agro-inoculated with RNA-2, no infection developed and the plants were also resistant to challenge with CPMV. By contrast, plants transgenic for RNA-2 became infected when agro-inoculated with RNA-1 and were fully susceptible to CPMV infection. The resistance of RNA-1 transgenic plants was shown to be related to the ability of RNA-1 to self-replicate and act as an amplicon. The ability of transgenically expressed RNA-2 to counteract the amplicon effect suggested that it encodes a suppressor of posttranscriptional gene silencing (PTGS). By examining the ability of portions of RNA-2 to reverse PTGS in N. benthamiana, we have identified the small (S) coat protein as the CPMV RNA-2-encoded suppressor of PTGS

  3. 7C.02: TRAINING AND ENVIRONMENTAL ENRICHMENT TO COUNTERACT COGNITIVE DECLINE: TRAIN THE BRAIN - EFFECTS ON CAROTID STRUCTURE AND FUNCTION.

    Science.gov (United States)

    Stea, F; Bruno, R; Ghiadoni, L; Faita, F; Di Lascio, N; Del Turco, S; Maffei, L; Tognoni, G; Taddei, S; Picano, E; Sicari, R

    2015-06-01

    Physical activity is beneficial to vascular health; on the other hand, vascular damage is associated with cognitive impairment. Both physical activity and a cognitively stimulating environment are known to delay the onset of dementia. The Train The Brain study evaluates the effectiveness of a comprehensive program of physical training and mental activity in delaying cognitive decline in elderly people with mild cognitive impairment, at the same time investigating the relationship between physical, vascular, neurological, and cognitive fitness : Elders age 65-89 were recruited with the help of family physicians and territorial services. All participants underwent a neurological and cardiologic evaluation. In the vascular study, carotid pressure was measured with the SphygmoCor system (AtCor, Australia); longitudinal ultrasound scans of the common carotid were performed and 10-second video clips were recorded to be analyzed offline through the Cardiovascular Suite software (Quipu srl, Italy), with the computation of diameter, intima-media thickness, wall cross-sectional area, distensibility coefficient, compliance, stiffness, and elastic modulus. Subjects classified as mild cognitive impairment at the neurological examination were randomized either to standard care, or a 7-month program of physical training and environmental stimulation (lectures, games, music, social activities) three hours a week. The evaluation was then repeated. Data were obtained for 57 patients who underwent training (T) and 30 controls (C). The only significant difference at baseline was in the distensibility coefficient (p = 0.045).(Figure is included in full-text article.)Vessel diameter increased in C and decreased in T; distensibility decreased in C; all carotid parameters were influenced by the combination of time and treatment, in a diverging trend, at a statistically significant level, while there was no effect on pressure. Introducing arterial pressures as covariates did not affect

  4. Examining food additives and spices for their anti-oxidant ability to counteract oxidative damage due to chronic exposure to free radicals from environmental pollutants

    Science.gov (United States)

    Martinez, Raul A., III

    The main objective of this work was to examine food additives and spices (from the Apiaceae family) to determine their antioxidant properties to counteract oxidative stress (damage) caused by Environmental pollutants. Environmental pollutants generate Reactive Oxygen species and Reactive Nitrogen species. Star anise essential oil showed lower antioxidant activity than extracts using DPPH scavenging. Dill Seed -- Anethum Graveolens -the monoterpene components of dill showed to activate the enzyme glutathione-S-transferase , which helped attach the antioxidant molecule glutathione to oxidized molecules that would otherwise do damage in the body. The antioxidant activity of extracts of dill was comparable with ascorbic acid, alpha-tocopherol, and quercetin in in-vitro systems. Black Cumin -- Nigella Sativa: was evaluated the method 1,1-diphenyl2-picrylhhydrazyl (DPPH) radical scavenging activity. Positive correlations were found between the total phenolic content in the black cumin extracts and their antioxidant activities. Caraway -- Carum Carvi: The antioxidant activity was evaluated by the scavenging effects of 1,1'-diphenyl-2-picrylhydrazyl (DPPH). Caraway showed strong antioxidant activity. Cumin -- Cuminum Cyminum - the major polyphenolic were extracted and separated by HPTLC. The antioxidant activity of the cumin extract was tested on 1,1'-diphenyl-2- picrylhydrazyl (DPPH) free radical scavenging. Coriander -- Coriandrum Sativum - the antioxidant and free-radical-scavenging property of the seeds was studied and also investigated whether the administration of seeds curtails oxidative stress. Coriander seed powder not only inhibited the process of Peroxidative damage, but also significantly reactivated the antioxidant enzymes and antioxidant levels. The seeds also showed scavenging activity against superoxides and hydroxyl radicals. The total polyphenolic content of the seeds was found to be 12.2 galic acid equivalents (GAE)/g while the total flavonoid content

  5. The angiotensin-(1-7/Mas axis counteracts angiotensin II-dependent and –independent pro-inflammatory signaling in human vascular smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Laura A Villalobos

    2016-12-01

    Full Text Available Background and aims: Targeting inflammation is nowadays considered as a challenging pharmacological strategy to prevent or delay the development of vascular diseases. Angiotensin-(1-7 is a member of the renin-angiotensin system (RAS that binds Mas receptors and has gained growing attention in the last years as a regulator of vascular homeostasis. Here, we explored the capacity of Ang-(1-7 to counteract human aortic smooth muscle cell (HASMC inflammation triggered by RAS-dependent and –independent stimuli, such as Ang II or interleukin (IL-1.Methods and Results: In cultured HASMC, the expression of iNOS and the release of nitric oxide were stimulated by both Ang II and IL-1, as determined by Western blot and indirect immunofluorescence or the Griess method, respectively. iNOS induction was inhibited by Ang-(1-7 in a concentration-dependent manner. This effect was equally blocked by two different Mas receptor antagonists, A779 and D-Pro7-Ang-(1-7, suggesting the participation of a unique Mas receptor subtype. Using pharmacological inhibitors, the induction of iNOS was proven to rely on the consecutive upstream activation of NADPH oxidase and NF-B. Indeed, Ang-(1-7 markedly inhibited the activation of the NADPH oxidase and subsequently of NF-B, as determined by lucigenin-derived chemiluminiscence and electromobility shift assay, respectively.Conclusion: Ang-(1-7 can act as a counter-regulator of the inflammation of vascular smooth muscle cells triggered by Ang II, but also by other stimuli beyond the RAS. Activating or mimicking the Ang-(1-7/Mas axis may represent a pharmacological opportunity to attenuate the pro-inflammatory environment that promotes and sustains the development of vascular diseases.

  6. A eukaryotic-acquired gene by a biotrophic phytopathogen allows prolonged survival on the host by counteracting the shut-down of plant photosynthesis

    KAUST Repository

    Garavaglia, Betiana S.

    2010-01-28

    Xanthomonas citri pv. citri, the bacteria responsible for citrus canker posses a biological active plant natriuretic peptide (PNP)-like protein, not present in any other bacteria. PNPs are a class of extracellular, systemically mobile peptides that elicit a number of plant responses important in homeostasis and growth. Previously, we showed that a Xanthomonas citri pv. citri mutant lacking the PNP-like protein XacPNP produced more necrotic lesions in citrus leaves than wild type infections and suggested a role for XacPNP in the regulation of host homeostasis. Here we have analyzed the proteome modifications observed in citrus leaves infected with the wild type and XacPNP deletion mutant bacteria. While both of them cause downregulation of enzymes related to photosynthesis as well as chloroplastic ribosomal proteins, proteins related to defense responses are up-regulated. However, leaves infiltrated with the XacPNP deletion mutant show a more pronounced decrease in photosynthetic proteins while no reduction in defense related proteins as compared to the wild-type pathogen. This suggests that XacPNP serves the pathogen to maintain host photosynthetic efficiency during pathogenesis. The results from the proteomics analyses are consistent with our chlorophyll fluorescence data and transcript analyses of defense genes that show a more marked reduction in photosynthesis in the mutant but no difference in the induction of genes diagnostic for biotic-stress responses. We therefore conclude that XacPNP counteracts the shut-down of host photosynthesis during infection and in that way maintains the tissue in better conditions, suggesting that the pathogen has adapted a host gene to modify its natural host and render it a better reservoir for prolonged bacterial survival and thus for further colonization. 2010 Garavaglia et al.

  7. A eukaryotic-acquired gene by a biotrophic phytopathogen allows prolonged survival on the host by counteracting the shut-down of plant photosynthesis.

    Science.gov (United States)

    Garavaglia, Betiana S; Thomas, Ludivine; Gottig, Natalia; Dunger, Germán; Garofalo, Cecilia G; Daurelio, Lucas D; Ndimba, Bongani; Orellano, Elena G; Gehring, Chris; Ottado, Jorgelina

    2010-01-28

    Xanthomonas citri pv. citri, the bacteria responsible for citrus canker posses a biological active plant natriuretic peptide (PNP)-like protein, not present in any other bacteria. PNPs are a class of extracellular, systemically mobile peptides that elicit a number of plant responses important in homeostasis and growth. Previously, we showed that a Xanthomonas citri pv. citri mutant lacking the PNP-like protein XacPNP produced more necrotic lesions in citrus leaves than wild type infections and suggested a role for XacPNP in the regulation of host homeostasis. Here we have analyzed the proteome modifications observed in citrus leaves infected with the wild type and XacPNP deletion mutant bacteria. While both of them cause down-regulation of enzymes related to photosynthesis as well as chloroplastic ribosomal proteins, proteins related to defense responses are up-regulated. However, leaves infiltrated with the XacPNP deletion mutant show a more pronounced decrease in photosynthetic proteins while no reduction in defense related proteins as compared to the wild-type pathogen. This suggests that XacPNP serves the pathogen to maintain host photosynthetic efficiency during pathogenesis. The results from the proteomics analyses are consistent with our chlorophyll fluorescence data and transcript analyses of defense genes that show a more marked reduction in photosynthesis in the mutant but no difference in the induction of genes diagnostic for biotic-stress responses. We therefore conclude that XacPNP counteracts the shut-down of host photosynthesis during infection and in that way maintains the tissue in better conditions, suggesting that the pathogen has adapted a host gene to modify its natural host and render it a better reservoir for prolonged bacterial survival and thus for further colonization.

  8. A eukaryotic-acquired gene by a biotrophic phytopathogen allows prolonged survival on the host by counteracting the shut-down of plant photosynthesis.

    Directory of Open Access Journals (Sweden)

    Betiana S Garavaglia

    Full Text Available Xanthomonas citri pv. citri, the bacteria responsible for citrus canker posses a biological active plant natriuretic peptide (PNP-like protein, not present in any other bacteria. PNPs are a class of extracellular, systemically mobile peptides that elicit a number of plant responses important in homeostasis and growth. Previously, we showed that a Xanthomonas citri pv. citri mutant lacking the PNP-like protein XacPNP produced more necrotic lesions in citrus leaves than wild type infections and suggested a role for XacPNP in the regulation of host homeostasis. Here we have analyzed the proteome modifications observed in citrus leaves infected with the wild type and XacPNP deletion mutant bacteria. While both of them cause down-regulation of enzymes related to photosynthesis as well as chloroplastic ribosomal proteins, proteins related to defense responses are up-regulated. However, leaves infiltrated with the XacPNP deletion mutant show a more pronounced decrease in photosynthetic proteins while no reduction in defense related proteins as compared to the wild-type pathogen. This suggests that XacPNP serves the pathogen to maintain host photosynthetic efficiency during pathogenesis. The results from the proteomics analyses are consistent with our chlorophyll fluorescence data and transcript analyses of defense genes that show a more marked reduction in photosynthesis in the mutant but no difference in the induction of genes diagnostic for biotic-stress responses. We therefore conclude that XacPNP counteracts the shut-down of host photosynthesis during infection and in that way maintains the tissue in better conditions, suggesting that the pathogen has adapted a host gene to modify its natural host and render it a better reservoir for prolonged bacterial survival and thus for further colonization.

  9. Transgene IL-6 Enhances DC-Stimulated CTL Responses by Counteracting CD4+25+Foxp3+ Regulatory T Cell Suppression via IL-6-Induced Foxp3 Downregulation

    Directory of Open Access Journals (Sweden)

    Kalpana Kalyanasundaram Bhanumathy

    2014-03-01

    Full Text Available Dendritic cells (DCs, the most potent antigen-presenting cells have been extensively applied in clinical trials for evaluation of antitumor immunity. However, the efficacy of DC-mediated cancer vaccines is still limited as they are unable to sufficiently break the immune tolerance. In this study, we constructed a recombinant adenoviral vector (AdVIL-6 expressing IL-6, and generated IL-6 transgene-engineered DC vaccine (DCOVA/IL-6 by transfection of murine bone marrow-derived ovalbumin (OVA-pulsed DCs (DCOVA with AdVIL-6. We then assessed DCOVA/IL-6-stimulated cytotoxic T-lymphocyte (CTL responses and antitumor immunity in OVA-specific animal tumor model. We demonstrate that DCOVA/IL-6 vaccine up-regulates expression of DC maturation markers, secretes transgene-encoded IL-6, and more efficiently stimulates OVA-specific CTL responses and therapeutic immunity against OVA-expressing B16 melanoma BL6-10OVA in vivo than the control DCOVA/Null vaccine. Moreover, DCOVA/IL-6-stimulated CTL responses were relatively maintained in mice with transfer of CD4+25+Foxp3+ Tr-cells, but significantly reduced when treated with anti-IL-6 antibody. In addition, we demonstrate that IL-6 down-regulates Foxp3-expression of CD4+25+Foxp3+ Tr-cells in vitro. Taken together, our results demonstrate that AdV-mediated IL-6 transgene-engineered DC vaccine stimulates potent CTL responses and antitumor immunity by counteracting CD4+25+ Tr immunosuppression via IL-6-induced Foxp3 down-regulation. Thus, IL-6 may be a good candidate for engineering DCs for cancer immunotherapy.

  10. Feline tetherin is characterized by a short N-terminal region and is counteracted by the feline immunodeficiency virus envelope glycoprotein.

    Science.gov (United States)

    Celestino, Michele; Calistri, Arianna; Del Vecchio, Claudia; Salata, Cristiano; Chiuppesi, Flavia; Pistello, Mauro; Borsetti, Alessandra; Palù, Giorgio; Parolin, Cristina

    2012-06-01

    Tetherin (BST2) is the host cell factor that blocks the particle release of some enveloped viruses. Two putative feline tetherin proteins differing at the level of the N-terminal coding region have recently been described and tested for their antiviral activity. By cloning and comparing the two reported feline tetherins (called here cBST2(504) and cBST2*) and generating specific derivative mutants, this study provides evidence that feline tetherin has a shorter intracytoplasmic domain than those of other known homologues. The minimal tetherin promoter was identified and assayed for its ability to drive tetherin expression in an alpha interferon-inducible manner. We also demonstrated that cBST2(504) is able to dimerize, is localized at the cellular membrane, and impairs human immunodeficiency virus type 1 (HIV-1) particle release, regardless of the presence of the Vpu antagonist accessory protein. While cBST2(504) failed to restrict wild-type feline immunodeficiency virus (FIV) egress, FIV mutants, bearing a frameshift at the level of the envelope-encoding region, were potently blocked. The transient expression of the FIV envelope glycoprotein was able to rescue mutant particle release from feline tetherin-positive cells but did not antagonize human BST2 activity. Moreover, cBST2(504) was capable of specifically immunoprecipitating the FIV envelope glycoprotein. Finally, cBST2(504) also exerted its function on HIV-2 ROD10 and on the simian immunodeficiency virus SIVmac239. Taken together, these results show that feline tetherin does indeed have a short N-terminal region and that the FIV envelope glycoprotein is the predominant factor counteracting tetherin restriction.

  11. A eukaryotic-acquired gene by a biotrophic phytopathogen allows prolonged survival on the host by counteracting the shut-down of plant photosynthesis

    KAUST Repository

    Garavaglia, Betiana S.; Thomas, Ludivine; Gottig, Natalia; Dunger, Germá n; Garofalo, Cecilia G.; Daurelio, Lucas D.; Ndimba, Bongani; Orellano, Elena G.; Gehring, Christoph A; Ottado, Jorgelina

    2010-01-01

    Xanthomonas citri pv. citri, the bacteria responsible for citrus canker posses a biological active plant natriuretic peptide (PNP)-like protein, not present in any other bacteria. PNPs are a class of extracellular, systemically mobile peptides that elicit a number of plant responses important in homeostasis and growth. Previously, we showed that a Xanthomonas citri pv. citri mutant lacking the PNP-like protein XacPNP produced more necrotic lesions in citrus leaves than wild type infections and suggested a role for XacPNP in the regulation of host homeostasis. Here we have analyzed the proteome modifications observed in citrus leaves infected with the wild type and XacPNP deletion mutant bacteria. While both of them cause downregulation of enzymes related to photosynthesis as well as chloroplastic ribosomal proteins, proteins related to defense responses are up-regulated. However, leaves infiltrated with the XacPNP deletion mutant show a more pronounced decrease in photosynthetic proteins while no reduction in defense related proteins as compared to the wild-type pathogen. This suggests that XacPNP serves the pathogen to maintain host photosynthetic efficiency during pathogenesis. The results from the proteomics analyses are consistent with our chlorophyll fluorescence data and transcript analyses of defense genes that show a more marked reduction in photosynthesis in the mutant but no difference in the induction of genes diagnostic for biotic-stress responses. We therefore conclude that XacPNP counteracts the shut-down of host photosynthesis during infection and in that way maintains the tissue in better conditions, suggesting that the pathogen has adapted a host gene to modify its natural host and render it a better reservoir for prolonged bacterial survival and thus for further colonization. 2010 Garavaglia et al.

  12. Pretreatment by low-dose fibrates protects against acute free fatty acid-induced renal tubule toxicity by counteracting PPARα deterioration

    International Nuclear Information System (INIS)

    Takahashi, Kyoko; Kamijo, Yuji; Hora, Kazuhiko; Hashimoto, Koji; Higuchi, Makoto; Nakajima, Takero; Ehara, Takashi; Shigematsu, Hidekazu; Gonzalez, Frank J.; Aoyama, Toshifumi

    2011-01-01

    Development of a preventive strategy against tubular damage associated with proteinuria is of great importance. Recently, free fatty acid (FFA) toxicities accompanying proteinuria were found to be a main cause of tubular damage, which was aggravated by insufficiency of peroxisome proliferator-activated receptor alpha (PPARα), suggesting the benefit of PPARα activation. However, an earlier study using a murine acute tubular injury model, FFA-overload nephropathy, demonstrated that high-dose treatment of PPARα agonist (0.5% clofibrate diet) aggravated the tubular damage as a consequence of excess serum accumulation of clofibrate metabolites due to decreased kidney elimination. To induce the renoprotective effects of PPARα agonists without drug accumulation, we tried a pretreatment study using low-dose clofibrate (0.1% clofibrate diet) using the same murine model. Low-dose clofibrate pretreatment prevented acute tubular injuries without accumulation of its metabolites. The tubular protective effects appeared to be associated with the counteraction of PPARα deterioration, resulting in the decrease of FFAs influx to the kidney, maintenance of fatty acid oxidation, diminution of intracellular accumulation of undigested FFAs, and attenuation of disease developmental factors including oxidative stress, apoptosis, and NFκB activation. These effects are common to other fibrates and dependent on PPARα function. Interestingly, however, clofibrate pretreatment also exerted PPARα-independent tubular toxicities in PPARα-null mice with FFA-overload nephropathy. The favorable properties of fibrates are evident when PPARα-dependent tubular protective effects outweigh their PPARα-independent tubular toxicities. This delicate balance seems to be easily affected by the drug dose. It will be important to establish the appropriate dosage of fibrates for treatment against kidney disease and to develop a novel PPARα activator that has a steady serum concentration regardless of

  13. GM-CSF ameliorates microvascular barrier integrity via pericyte-derived Ang-1 in wound healing.

    Science.gov (United States)

    Yan, Min; Hu, Yange; Yao, Min; Bao, Shisan; Fang, Yong

    2017-11-01

    Skin wound healing involves complex coordinated interactions of cells, tissues, and mediators. Maintaining microvascular barrier integrity is one of the key events for endothelial homeostasis during wound healing. Vasodilation is observed after vasoconstriction, which causes blood vessels to become porous, facilitates leukocyte infiltration and aids angiogenesis at the wound-area, postinjury. Eventually, vessel integrity has to be reestablished for vascular maturation. Numerous studies have found that granulocyte macrophage colony-stimulating factor (GM-CSF) accelerates wound healing by inducing recruitment of repair cells into the injury area and releases of cytokines. However, whether GM-CSF is involving in the maintaining of microvascular barrier integrity and the underlying mechanism remain still unclear. Aim of this study was to investigate the effects of GM-CSF on modulation of microvascular permeability in wound healing and underlying mechanisms. Wound closure and microvascular leakage was investigated using a full-thickness skin wound mouse model after GM-CSF intervention. The endothelial permeability was measured by Evans blue assay in vivo and in vitro endothelium/pericyte co-culture system using a FITC-Dextran permeability assay. To identify the source of angiopoietin-1 (Ang-1), double staining is used in vivo and ELISA and qPCR are used in vitro. To determine the specific effect of Ang-1 on GM-CSF maintaining microvascular stabilization, Ang-1 siRNA was applied to inhibit Ang-1 production in vivo and in vitro. Wound closure was significantly accelerated and microvascular leakage was ameliorated after GM-CSF treatment in mouse wound sites. GM-CSF decreased endothelial permeability through tightening endothelial junctions and increased Ang-1 protein level that was derived by perictye. Furthermore, applications of siRNAAng-1 inhibited GM-CSF mediated protection of microvascular barrier integrity both in vivo and in vitro. Our data indicate that GM

  14. Increased topsoil carbon stock across China's forests.

    Science.gov (United States)

    Yang, Yuanhe; Li, Pin; Ding, Jinzhi; Zhao, Xia; Ma, Wenhong; Ji, Chengjun; Fang, Jingyun

    2014-08-01

    Biomass carbon accumulation in forest ecosystems is a widespread phenomenon at both regional and global scales. However, as coupled carbon-climate models predicted, a positive feedback could be triggered if accelerated soil carbon decomposition offsets enhanced vegetation growth under a warming climate. It is thus crucial to reveal whether and how soil carbon stock in forest ecosystems has changed over recent decades. However, large-scale changes in soil carbon stock across forest ecosystems have not yet been carefully examined at both regional and global scales, which have been widely perceived as a big bottleneck in untangling carbon-climate feedback. Using newly developed database and sophisticated data mining approach, here we evaluated temporal changes in topsoil carbon stock across major forest ecosystem in China and analysed potential drivers in soil carbon dynamics over broad geographical scale. Our results indicated that topsoil carbon stock increased significantly within all of five major forest types during the period of 1980s-2000s, with an overall rate of 20.0 g C m(-2) yr(-1) (95% confidence interval, 14.1-25.5). The magnitude of soil carbon accumulation across coniferous forests and coniferous/broadleaved mixed forests exhibited meaningful increases with both mean annual temperature and precipitation. Moreover, soil carbon dynamics across these forest ecosystems were positively associated with clay content, with a larger amount of SOC accumulation occurring in fine-textured soils. In contrast, changes in soil carbon stock across broadleaved forests were insensitive to either climatic or edaphic variables. Overall, these results suggest that soil carbon accumulation does not counteract vegetation carbon sequestration across China's forest ecosystems. The combination of soil carbon accumulation and vegetation carbon sequestration triggers a negative feedback to climate warming, rather than a positive feedback predicted by coupled carbon-climate models

  15. Empowerment and its implementation in the process of counteracting the phenomenon of youth and adult social exclusion – report on participation in an international project under the 2014-2016 Erasmus + Strategic Partnership project

    Directory of Open Access Journals (Sweden)

    Jolanta Jarczyńska

    2017-07-01

    Full Text Available The aim of the article is to describe the empowerment process and its implementation in social work in the context of counteracting social exclusion in youth and adults based on the example of the project carried out in the years 2014-2016, titled: “Development of the empowerment of educators and beneficiaries in the field of youth at risk and social exclusion”, co-financed from European Union funds within the Erasmus + programme, Action 2: Strategic partnership of professional teaching and training, Grant No. 2014-1-FR01-KA2026-008728. The English language concept category of empowerment, which does not have a satisfactory equivalent term in the Polish language, was operationalised in this article. The essence of empowerment in the context of social work was described in the article, pointing to its significance mainly in the scope of counteracting the process of youth and adult social exclusion. Furthermore, the main assumptions of the implemented international project were set out in the ambit of the development of the empowerment of educators as well as of beneficiaries working with persons at risk of social exclusion, and the relationship and reflections of one of the project participants were also shown. An attempt was made in the article on the basis of the experiences gathered within the performance of the international research project to assess the course of the empowerment process and its usefulness in searching for solutions for educational practices in the domain of the social exclusion phenomenon.

  16. Predicting Polylepis distribution: vulnerable and increasingly important Andean woodlands

    Directory of Open Access Journals (Sweden)

    Brian R. Zutta

    2012-11-01

    Full Text Available Polylepis woodlands are a vital resource for preserving biodiversity and hydrological functions, which will be altered by climate change and challenge the sustainability of local human communities. However, these highaltitude Andean ecosystems are becoming increasingly vulnerable due to anthropogenic pressure including fragmentation, deforestation and the increase in livestock. Predicting the distribution of native woodlands has become increasingly important to counteract the negative effects of climate change through reforestation and conservation. The objective of this study was to develop and analyze the distribution models of two species that form extensive woodlands along the Andes, namely Polylepis sericea and P. weberbaueri. This study utilized the program Maxent, climate and remotely sensed environmental layers at 1 km resolution. The predicted distribution model for P. sericea indicated that the species could be located in a variety of habitats along the Andean Cordillera, while P. weberbaueri was restricted to the high elevations of southern Peru and Bolivia. For both species, elevation and temperature metrics were the most significant factors for predicted distribution. Further model refinement of Polylepis and other Andean species using increasingly available satellite data demonstrate the potential to help define areas of diversity and improve conservation strategies for the Andes.

  17. Prolonged fasting increases glutathione biosynthesis in postweaned northern elephant seals

    Science.gov (United States)

    Vázquez-Medina, José Pablo; Zenteno-Savín, Tania; Forman, Henry Jay; Crocker, Daniel E.; Ortiz, Rudy M.

    2011-01-01

    SUMMARY Northern elephant seals experience prolonged periods of absolute food and water deprivation (fasting) while breeding, molting or weaning. The postweaning fast in elephant seals is characterized by increases in the renin–angiotensin system, expression of the oxidant-producing protein Nox4, and NADPH oxidase activity; however, these increases are not correlated with increased oxidative damage or inflammation. Glutathione (GSH) is a potent reductant and a cofactor for glutathione peroxidases (GPx), glutathione-S transferases (GST) and 1-cys peroxiredoxin (PrxVI) and thus contributes to the removal of hydroperoxides, preventing oxidative damage. The effects of prolonged food deprivation on the GSH system are not well described in mammals. To test our hypothesis that GSH biosynthesis increases with fasting in postweaned elephant seals, we measured circulating and muscle GSH content at the early and late phases of the postweaning fast in elephant seals along with the activity/protein content of glutamate-cysteine ligase [GCL; catalytic (GCLc) and modulatory (GCLm) subunits], γ-glutamyl transpeptidase (GGT), glutathione disulphide reductase (GR), glucose-6-phosphate dehydrogenase (G6PDH), GST and PrxVI, as well as plasma changes in γ-glutamyl amino acids, glutamate and glutamine. GSH increased two- to four-fold with fasting along with a 40–50% increase in the content of GCLm and GCLc, a 75% increase in GGT activity, a two- to 2.5-fold increase in GR, G6PDH and GST activities and a 30% increase in PrxVI content. Plasma γ-glutamyl glutamine, γ-glutamyl isoleucine and γ-glutamyl methionine also increased with fasting whereas glutamate and glutamine decreased. Results indicate that GSH biosynthesis increases with fasting and that GSH contributes to counteracting hydroperoxide production, preventing oxidative damage in fasting seals. PMID:21430206

  18. Increased SRP reactor power

    International Nuclear Information System (INIS)

    MacAfee, I.M.

    1983-01-01

    Major changes in the current reactor hydraulic systems could be made to achieve a total of about 1500 MW increase of reactor power for P, K, and C reactors. The changes would be to install new, larger heat exchangers in the reactor buildings to increase heat transfer area about 24%, to increase H 2 O flow about 30% per reactor, to increase D 2 O flow 15 to 18% per reactor, and increase reactor blanket gas pressure from 5 psig to 10 psig. The increased reactor power is possible because of reduced inlet temperature of reactor coolant, increased heat removal capacity, and increased operating pressure (larger margin from boiling). The 23% reactor power increase, after adjustment for increased off-line time for reactor reloading, will provide a 15% increase of production from P, K, and C reactors. Restart of L Reactor would increase SRP production 33%

  19. A genome-wide RNAi screen identifies FOXO4 as a metastasis-suppressor through counteracting PI3K/AKT signal pathway in prostate cancer.

    Directory of Open Access Journals (Sweden)

    Bing Su

    Full Text Available Activation of the PI3K/AKT signal pathway is a known driving force for the progression to castration-recurrent prostate cancer (CR-CaP, which constitutes the major lethal phenotype of CaP. Here, we identify using a genomic shRNA screen the PI3K/AKT-inactivating downstream target, FOXO4, as a potential CaP metastasis suppressor. FOXO4 protein levels inversely correlate with the invasive potential of a panel of human CaP cell lines, with decreased mRNA levels correlating with increased incidence of clinical metastasis. Knockdown (KD of FOXO4 in human LNCaP cells causes increased invasion in vitro and lymph node (LN metastasis in vivo without affecting indices of proliferation or apoptosis. Increased Matrigel invasiveness was found by KD of FOXO1 but not FOXO3. Comparison of differentially expressed genes affected by FOXO4-KD in LNCaP cells in culture, in primary tumors and in LN metastases identified a panel of upregulated genes, including PIP, CAMK2N1, PLA2G16 and PGC, which, if knocked down by siRNA, could decrease the increased invasiveness associated with FOXO4 deficiency. Although only some of these genes encode FOXO promoter binding sites, they are all RUNX2-inducible, and RUNX2 binding to the PIP promoter is increased in FOXO4-KD cells. Indeed, the forced expression of FOXO4 reversed the increased invasiveness of LNCaP/shFOXO4 cells; the forced expression of FOXO4 did not alter RUNX2 protein levels, yet it decreased RUNX2 binding to the PIP promoter, resulting in PIP downregulation. Finally, there was a correlation between FOXO4, but not FOXO1 or FOXO3, downregulation and decreased metastasis-free survival in human CaP patients. Our data strongly suggest that increased PI3K/AKT-mediated metastatic invasiveness in CaP is associated with FOXO4 loss, and that mechanisms to induce FOXO4 re-expression might suppress CaP metastatic aggressiveness.

  20. Cinnamon counteracts the negative effects of a high fat/high fructose diet on behavior, brain insulin signaling and Alzheimer-associated changes.

    Directory of Open Access Journals (Sweden)

    Richard A Anderson

    Full Text Available Insulin resistance leads to memory impairment. Cinnamon (CN improves peripheral insulin resistance but its effects in the brain are not known. Changes in behavior, insulin signaling and Alzheimer-associated mRNA expression in the brain were measured in male Wistar rats fed a high fat/high fructose (HF/HFr diet to induce insulin resistance, with or without CN, for 12 weeks. There was a decrease in insulin sensitivity associated with the HF/HFr diet that was reversed by CN. The CN fed rats were more active in a Y maze test than rats fed the control and HF/HFr diets. The HF/HFr diet fed rats showed greater anxiety in an elevated plus maze test that was lessened by feeding CN. The HF/HFr diet also led to a down regulation of the mRNA coding for GLUT1 and GLUT3 that was reversed by CN in the hippocampus and cortex. There were increases in Insr, Irs1 and Irs2 mRNA in the hippocampus and cortex due to the HF/HFr diet that were not reversed by CN. Increased peripheral insulin sensitivity was also associated with increased glycogen synthase in both hippocampus and cortex in the control and HF/HFr diet animals fed CN. The HF/HFr diet induced increases in mRNA associated with Alzheimers including PTEN, Tau and amyloid precursor protein (App were also alleviated by CN. In conclusion, these data suggest that the negative effects of a HF/HFr diet on behavior, brain insulin signaling and Alzheimer-associated changes were alleviated by CN suggesting that neuroprotective effects of CN are associated with improved whole body insulin sensitivity and related changes in the brain.

  1. The protective arm of the renin-angiotensin system may counteract the intense inflammatory process in fetuses with posterior urethral valves.

    Science.gov (United States)

    Rocha, Natalia P; Bastos, Fernando M; Vieira, Érica L M; Prestes, Thiago R R; Silveira, Katia D da; Teixeira, Mauro M; Simões E Silva, Ana Cristina

    2018-03-11

    Posterior urethral valve is the most common lower urinary tract obstruction in male children. A high percentage of patients with posterior urethral valve evolve to end-stage renal disease. Previous studies showed that cytokines, chemokines, and components of the renin-angiotensin system contribute to the renal damage in obstructive uropathies. The authors recently found that urine samples from fetuses with posterior urethral valve have increased levels of inflammatory molecules. The aim of this study was to measure renin-angiotensin system molecules and to investigate their correlation with previously detected inflammatory markers in the same urine samples of fetuses with posterior urethral valve. Urine samples from 24 fetuses with posterior urethral valve were collected and compared to those from 22 healthy male newborns at the same gestational age (controls). Renin-angiotensin system components levels were measured by enzyme-linked immunosorbent assay. Fetuses with posterior urethral valve presented increased urinary levels of angiotensin (Ang) I, Ang-(1-7) and angiotensin-converting enzyme 2 in comparison with controls. ACE levels were significantly reduced and Ang II levels were similar in fetuses with posterior urethral valve in comparison with controls. Increased urinary levels of angiotensin-converting enzyme 2 and of Ang-(1-7) in fetuses with posterior urethral valve could represent a regulatory response to the intense inflammatory process triggered by posterior urethral valve. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  2. Acute up-regulation of the rat brain somatostatin receptor-effector system by leptin is related to activation of insulin signaling and may counteract central leptin actions.

    Science.gov (United States)

    Perianes-Cachero, A; Burgos-Ramos, E; Puebla-Jiménez, L; Canelles, S; Frago, L M; Hervás-Aguilar, A; de Frutos, S; Toledo-Lobo, M V; Mela, V; Viveros, M P; Argente, J; Chowen, J A; Arilla-Ferreiro, E; Barrios, V

    2013-11-12

    Leptin and somatostatin (SRIF) have opposite effects on food seeking and ingestive behaviors, functions partially regulated by the frontoparietal cortex and hippocampus. Although it is known that the acute suppression of food intake mediated by leptin decreases with time, the counter-regulatory mechanisms remain unclear. Our aims were to analyze the effect of acute central leptin infusion on the SRIF receptor-effector system in these areas and the implication of related intracellular signaling mechanisms in this response. We studied 20 adult male Wister rats including controls and those treated intracerebroventricularly with a single dose of 5 μg of leptin and sacrificed 1 or 6h later. Density of SRIF receptors was unchanged at 1h, whereas leptin increased the density of SRIF receptors at 6h, which was correlated with an elevated capacity of SRIF to inhibit forskolin-stimulated adenylyl cyclase activity in both areas. The functional capacity of SRIF receptors was unaltered as cell membrane levels of αi1 and αi2 subunits of G inhibitory proteins were unaffected in both brain areas. The increased density of SRIF receptors was due to enhanced SRIF receptor subtype 2 (sst2) protein levels that correlated with higher mRNA levels for this receptor. These changes in sst2 mRNA levels were concomitant with increased activation of the insulin signaling, c-Jun and cyclic AMP response element-binding protein (CREB); however, activation of signal transducer and activator of transcription 3 was reduced in the cortex and unchanged in the hippocampus and suppressor of cytokine signaling 3 remained unchanged in these areas. In addition, the leptin antagonist L39A/D40A/F41A blocked the leptin-induced changes in SRIF receptors, leptin signaling and CREB activation. In conclusion, increased activation of insulin signaling after leptin infusion is related to acute up-regulation of the SRIF receptor-effector system that may antagonize short-term leptin actions in the rat brain

  3. CyPPA, a Positive SK3/SK2 Modulator, Reduces Activity of Dopaminergic Neurons, Inhibits Dopamine Release, and Counteracts Hyperdopaminergic Behaviors Induced by Methylphenidate

    DEFF Research Database (Denmark)

    Herrik, Kjartan F; Redrobe, John P; Holst, Dorte

    2012-01-01

    Dopamine (DA) containing midbrain neurons play critical roles in several psychiatric and neurological diseases, including schizophrenia and attention deficit hyperactivity disorder, and the substantia nigra pars compacta neurons selectively degenerate in Parkinson's disease. Pharmacological......]-amine (CyPPA), a subtype-selective positive modulator of SK channels (SK3¿>¿SK2¿>¿>¿>¿SK1, IK), decreased spontaneous firing rate, increased the duration of the apamin-sensitive afterhyperpolarization, and caused an activity-dependent inhibition of current-evoked action potentials in DA neurons from both...

  4. Rosmarinic acid counteracts activation of hepatic stellate cells via inhibiting the ROS-dependent MMP-2 activity: Involvement of Nrf2 antioxidant system

    International Nuclear Information System (INIS)

    Lu, Changfang; Zou, Yu; Liu, Yuzhang; Niu, Yingcai

    2017-01-01

    Recently, oxidative stress is involved in hepatofibrogenesis. Matrix metalloproteinase-2 (MMP-2) is required for activation of hepatic stellate cells (HSCs) in response to reactive oxygen species (ROS). This study was designed to explore the hypothesis that the inhibitory effect of rosmarinic acid (RA) on HSCs activation might mainly result from its antioxidant capability by increasing the synthesis of glutathione (GSH) involved in nuclear factor kappa B (NF-κB)-dependent inhibition of MMP-2 activity. Here, we demonstrate that RA reverses activated HSCs to quiescent cells. Concomitantly, RA inhibits MMP-2 activity. RNA interference-imposed knockdown of NF-κB abolished down-regulation of MMP-2 by RA. RA-mediated inactivation of NF-κB could be blocked by the diphenyleneiodonium chloride (DPI; a ROS inhibitor). Conversely, transfection of dominant-negative (DN) mutant of extracellular signal-regulated kinases 2 (ERK2), c-Jun N-terminal kinase 1 (JNK1), or p38α kinase had no such effect. Simultaneously, RA suppresses ROS generation and lipid peroxidation (LPO) whereas increases cellular GSH in HSC-T6 cells. Furthermore, RA significantly increased antioxidant response element (ARE)-mediated luciferase activity, nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and catalytic subunits from glutamate cysteine ligase (GCLc) expression, but not modulatory subunits from GCL (GCLm). RA-mediated up-regulation of GClc is inhibited by the shRNA-induced Nrf2 knockdown. The knocking down of Nrf2 or buthionine sulfoximine (a GCL inhibitor) abolished RA-mediated inhibition of ROS. Collectively, these results provide novel insights into the mechanisms of RA as an antifibrogenic candidate in the prevention and treatment of liver fibrosis. - Highlights: • RA reverses activated HSCs to quiescent cells. • RA suppresses MMP-2 activity through a NF-κB-dependent pathway. • Inhibition of oxidative stress by RA is dependent on nuclear translocation of Nrf2

  5. Rosmarinic acid counteracts activation of hepatic stellate cells via inhibiting the ROS-dependent MMP-2 activity: Involvement of Nrf2 antioxidant system

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Changfang; Zou, Yu; Liu, Yuzhang; Niu, Yingcai, E-mail: nyc1968@126.com

    2017-03-01

    Recently, oxidative stress is involved in hepatofibrogenesis. Matrix metalloproteinase-2 (MMP-2) is required for activation of hepatic stellate cells (HSCs) in response to reactive oxygen species (ROS). This study was designed to explore the hypothesis that the inhibitory effect of rosmarinic acid (RA) on HSCs activation might mainly result from its antioxidant capability by increasing the synthesis of glutathione (GSH) involved in nuclear factor kappa B (NF-κB)-dependent inhibition of MMP-2 activity. Here, we demonstrate that RA reverses activated HSCs to quiescent cells. Concomitantly, RA inhibits MMP-2 activity. RNA interference-imposed knockdown of NF-κB abolished down-regulation of MMP-2 by RA. RA-mediated inactivation of NF-κB could be blocked by the diphenyleneiodonium chloride (DPI; a ROS inhibitor). Conversely, transfection of dominant-negative (DN) mutant of extracellular signal-regulated kinases 2 (ERK2), c-Jun N-terminal kinase 1 (JNK1), or p38α kinase had no such effect. Simultaneously, RA suppresses ROS generation and lipid peroxidation (LPO) whereas increases cellular GSH in HSC-T6 cells. Furthermore, RA significantly increased antioxidant response element (ARE)-mediated luciferase activity, nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and catalytic subunits from glutamate cysteine ligase (GCLc) expression, but not modulatory subunits from GCL (GCLm). RA-mediated up-regulation of GClc is inhibited by the shRNA-induced Nrf2 knockdown. The knocking down of Nrf2 or buthionine sulfoximine (a GCL inhibitor) abolished RA-mediated inhibition of ROS. Collectively, these results provide novel insights into the mechanisms of RA as an antifibrogenic candidate in the prevention and treatment of liver fibrosis. - Highlights: • RA reverses activated HSCs to quiescent cells. • RA suppresses MMP-2 activity through a NF-κB-dependent pathway. • Inhibition of oxidative stress by RA is dependent on nuclear translocation of Nrf2

  6. Xanthomonas campestris RpfB is a Fatty Acyl-CoA Ligase Required to Counteract the Thioesterase Activity of the RpfF Diffusible Signal Factor (DSF) Synthase

    Science.gov (United States)

    Bi, Hongkai; Yu, Yonghong; Dong, Huijuan; Wang, Haihong; Cronan, John E.

    2014-01-01

    SUMMARY In Xanthomonas campestris pv. campestris (Xcc), the proteins encoded by the rpf (regulator of pathogenicity factor) gene cluster produce and sense a fatty acid signal molecule called diffusible signaling factor (DSF, 2(Z)-11-methyldodecenoic acid). RpfB was reported to be involved in DSF processing and was predicted to encode an acyl-CoA ligase. We report that RpfB activates a wide range of fatty acids to their CoA esters in vitro. Moreover, RpfB can functionally replace the paradigm bacterial acyl-CoA ligase, Escherichia coli FadD, in the E. coli β-oxidation pathway and deletion of RpfB from the Xcc genome results in a strain unable to utilize fatty acids as carbon sources. An essential RpfB function in the pathogenicity factor pathway was demonstrated by the properties of a strain deleted for both the rpfB and rpfC genes. The ΔrpfB ΔrpfC strain grew poorly and lysed upon entering stationary phase. Deletion of rpfF, the gene encoding the DSF synthetic enzyme, restored normal growth to this strain. RpfF is a dual function enzyme that synthesizes DSF by dehydration of a 3-hydroxyacyl-acyl carrier protein (ACP) fatty acid synthetic intermediate and also cleaves the thioester bond linking DSF to ACP. However, the RpfF thioesterase activity is of broad specificity and upon elimination of its RpfC inhibitor RpfF attains maximal activity and its thioesterase activity proceeds to block membrane lipid synthesis by cleavage of acyl-ACP intermediates. This resulted in release of the nascent acyl chains to the medium as free fatty acids. This lack of acyl chains for phospholipid synthesis results in cell lysis unless RpfB is present to counteract the RpfF thioesterase activity by catalyzing uptake and activation of the free fatty acids to give acyl-CoAs that can be utilized to restore membrane lipid synthesis. Heterologous expression of a different fatty acid activating enzyme, the Vibrio harveyi acyl-ACP synthetase, replaced RpfB in counteracting the effects of

  7. The small-molecule kinase inhibitor D11 counteracts 17-AAG-mediated up-regulation of HSP70 in brain cancer cells.

    Science.gov (United States)

    Schaefer, Susanne; Svenstrup, Tina H; Guerra, Barbara

    2017-01-01

    Many types of cancer express high levels of heat shock proteins (HSPs) that are molecular chaperones regulating protein folding and stability ensuring protection of cells from potentially lethal stress. HSPs in cancer cells promote survival, growth and spreading even in situations of growth factors deprivation by associating with oncogenic proteins responsible for cell transformation. Hence, it is not surprising that the identification of potent inhibitors of HSPs, notably HSP90, has been the primary research focus, in recent years. Exposure of cancer cells to HSP90 inhibitors, including 17-AAG, has been shown to cause resistance to chemotherapeutic treatment mostly attributable to induction of the heat shock response and increased cellular levels of pro-survival chaperones. In this study, we show that treatment of glioblastoma cells with 17-AAG leads to HSP90 inhibition indicated by loss of stability of the EGFR client protein, and significant increase in HSP70 expression. Conversely, co-treatment with the small-molecule kinase inhibitor D11 leads to suppression of the heat shock response and inhibition of HSF1 transcriptional activity. Beside HSP70, Western blot and differential mRNA expression analysis reveal that combination treatment causes strong down-regulation of the small chaperone protein HSP27. Finally, we demonstrate that incubation of cells with both agents leads to enhanced cytotoxicity and significantly high levels of LC3-II suggesting autophagy induction. Taken together, results reported here support the notion that including D11 in future treatment regimens based on HSP90 inhibition can potentially overcome acquired resistance induced by the heat shock response in brain cancer cells.

  8. Hydrogen sulfide regulates the levels of key metabolites and antioxidant defense system to counteract oxidative stress in pepper (Capsicum annuum L.) plants exposed to high zinc regime.

    Science.gov (United States)

    Kaya, Cengiz; Ashraf, Muhammad; Akram, Nudrat Aisha

    2018-02-21

    In the present experiment, we aimed to test the impact of hydrogen sulfide (H 2 S) on growth, key oxidant such as hydrogen peroxide, mineral elements, and antioxidative defense in Capia-type red sweet pepper (Capsicum annuum L.) plants subjected to high concentration of zinc (Zn). A factorial experiment was designed with two Zn levels (0.05 and 0.5 mM) and 0.2 mM sodium hydrosulfide (NaHS) as a donor of H 2 S supplied in combination plus nutrient solution through the root zone. High level of Zn led to reduce dry mass, chlorophyll pigments, fruit yield, leaf maximum fluorescence, and relative water content, but enhanced endogenous hydrogen peroxide (H 2 O 2 ), free proline, malondialdehyde (MDA), electrolyte leakage (EL), H 2 S, as well as the activities of peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD) enzymes. Exogenously applied NaHS significantly enhanced plant growth, fruit yield, water status, the levels of H 2 S and proline as well as the activities of different antioxidant enzymes, while it significantly suppressed EL, MDA, and H 2 O 2 contents in the pepper plants receiving low level Zn. NaHS application to the control plants did not significantly change all these parameters tested except the dry matter which increased significantly. High Zn regime led to increase intrinsic Zn levels in the leaves and roots, but it lowered leaf nitrogen (N), phosphorus (P), and iron (Fe) concentrations. However, NaHS reduces the Zn conc. and enhances Fe and N in leaf and root organs. It can be concluded that NaHS can mitigate the harmful effects of Zn on plant growth particularly by lowering the concentrations of H 2 O 2 , Zn, EL, and MDA, and enhancing the activities of enzymatic antioxidants and levels of essential nutrients in pepper plants.

  9. Combination of DFP and Taurine Counteracts the Aluminum-Induced Alterations in Oxidative Stress and ATPase in Cortex and Blood of Rats.

    Science.gov (United States)

    Feng, Tong; Liu, Ping; Zhang, Zhen; Hu, Jinyu; Kong, Zhengqiao

    2016-11-01

    The study investigated the combined effect of 1,2-dimethyl-3-hydroxypyrid-4-one (DFP) and taurine on aluminum (Al) toxicity in cortex and blood of rats. The control group received 1 ml/kg/day saline solution for 8 weeks. Other animals were exposed to Al at a dose of 281.40 mg/kg/day orally for 4 weeks. Then, they were administered with 1 ml/kg/day saline solution, 400 mg/(kg·day) taurine, 13.82 mg/(kg·day) DFP, 27.44 mg/(kg·day) DFP, 400 mg/(kg·day) taurine +13.82 mg/(kg·day) DFP, and 400 mg/(kg·day) taurine +27.44 mg/(kg·day) DFP for 4 weeks. The changes in markers of oxidative stress, activities of antioxidant enzymes, and triphosphatase (ATPase) in the cortex and blood were determined. Administration of Al led to significant increase in the malondialdehyde (MDA) level and decrease in the activities of antioxidant enzymes, Na + K + -ATPase, Mg 2+ -ATPase, and Ca 2+ -ATPase in the cortex and blood, compared with the control group. DFP was observed to reverse alteration of these parameters except for Ca 2+ -ATPase activity. Treatment with taurine caused significant increase of GSH-Px activity and decrease of the MDA level in the cortex and serum and rise of Na + K + -ATPase in the blood. Effects of DFP combined with taurine were investigated and found to provide a more significant benefit than either drug alone. Combined intake of taurine and DFP could achieve an optimum effect of therapy for Al exposure.

  10. Allergen-specific Th1 cells counteract efferent Th2 cell-dependent bronchial hyperresponsiveness and eosinophilic inflammation partly via IFN-gamma.

    Science.gov (United States)

    Huang, T J; MacAry, P A; Eynott, P; Moussavi, A; Daniel, K C; Askenase, P W; Kemeny, D M; Chung, K F

    2001-01-01

    Th2 T cell immune-driven inflammation plays an important role in allergic asthma. We studied the effect of counterbalancing Th1 T cells in an asthma model in Brown Norway rats that favors Th2 responses. Rats received i.v. transfers of syngeneic allergen-specific Th1 or Th2 cells, 24 h before aerosol exposure to allergen, and were studied 18-24 h later. Adoptive transfer of OVA-specific Th2 cells, but not Th1 cells, and OVA, but not BSA exposure, induced bronchial hyperresponsiveness (BHR) to acetylcholine and eosinophilia in a cell number-dependent manner. Importantly, cotransfer of OVA-specific Th1 cells dose-dependently reversed BHR and bronchoalveolar lavage (BAL) eosinophilia, but not mucosal eosinophilia. OVA-specific Th1 cells transferred alone induced mucosal eosinophilia, but neither BHR nor BAL eosinophilia. Th1 suppression of BHR and BAL eosinophilia was allergen specific, since cotransfer of BSA-specific Th1 cells with the OVA-specific Th2 cells was not inhibitory when OVA aerosol alone was used, but was suppressive with OVA and BSA challenge. Furthermore, recipients of Th1 cells alone had increased gene expression for IFN-gamma in the lungs, while those receiving Th2 cells alone showed increased IL-4 mRNA. Importantly, induction of these Th2 cytokines was inhibited in recipients of combined Th1 and Th2 cells. Anti-IFN-gamma treatment attenuated the down-regulatory effect of Th1 cells. Allergen-specific Th1 cells down-regulate efferent Th2 cytokine-dependent BHR and BAL eosinophilia in an asthma model via mechanisms that depend on IFN-gamma. Therapy designed to control the efferent phase of established asthma by augmenting down-regulatory Th1 counterbalancing mechanisms should be effective.

  11. Creatine, Similar to Ketamine, Counteracts Depressive-Like Behavior Induced by Corticosterone via PI3K/Akt/mTOR Pathway.

    Science.gov (United States)

    Pazini, Francis L; Cunha, Mauricio P; Rosa, Julia M; Colla, André R S; Lieberknecht, Vicente; Oliveira, Ágatha; Rodrigues, Ana Lúcia S

    2016-12-01

    Ketamine has emerged as a novel strategy to treat refractory depression, producing rapid remission, but elicits some side effects that limit its use. In an attempt to investigate a safer compound that may afford an antidepressant effect similar to ketamine, this study examined the effects of the ergogenic compound creatine in a model of depression, and the involvement of phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in its effect. In order to induce a depressive-like behavior, mice were administered with corticosterone (20 mg/kg, per os (p.o.)) for 21 days. This treatment increased immobility time in the tail suspension test (TST), an effect abolished by a single administration of creatine (10 mg/kg, p.o.) or ketamine (1 mg/kg, i.p.), but not by fluoxetine (10 mg/kg, p.o., conventional antidepressant). Treatment of mice with wortmannin (PI3K inhibitor, 0.1 μg/site, intracerebroventricular (i.c.v.)) or rapamycin (mTOR inhibitor, 0.2 nmol/site, i.c.v.) abolished the anti-immobility effect of creatine and ketamine. None of the treatments affected locomotor activity of mice. The immunocontents of p-mTOR, p-p70S6 kinase (p70S6K), and postsynaptic density-95 protein (PSD95) were increased by creatine and ketamine in corticosterone or vehicle-treated mice. Moreover, corticosterone-treated mice presented a decreased hippocampal brain-derived neurotrophic factor (BDNF) level, an effect abolished by creatine or ketamine. Altogether, the results indicate that creatine shares with ketamine the ability to acutely reverse the corticosterone-induced depressive-like behavior by a mechanism dependent on PI3K/AKT/mTOR pathway, and modulation of the synaptic protein PSD95 as well as BDNF in the hippocampus, indicating the relevance of targeting these proteins for the management of depressive disorders. Moreover, we suggest that creatine should be further investigated as a possible fast-acting antidepressant.

  12. Effects of Nandrolone in the Counteraction of Skeletal Muscle Atrophy in a Mouse Model of Muscle Disuse: Molecular Biology and Functional Evaluation.

    Directory of Open Access Journals (Sweden)

    Giulia Maria Camerino

    Full Text Available Muscle disuse produces severe atrophy and a slow-to-fast phenotype transition in the postural Soleus (Sol muscle of rodents. Antioxidants, amino-acids and growth factors were ineffective to ameliorate muscle atrophy. Here we evaluate the effects of nandrolone (ND, an anabolic steroid, on mouse skeletal muscle atrophy induced by hindlimb unloading (HU. Mice were pre-treated for 2-weeks before HU and during the 2-weeks of HU. Muscle weight and total protein content were reduced in HU mice and a restoration of these parameters was found in ND-treated HU mice. The analysis of gene expression by real-time PCR demonstrates an increase of MuRF-1 during HU but minor involvement of other catabolic pathways. However, ND did not affect MuRF-1 expression. The evaluation of anabolic pathways showed no change in mTOR and eIF2-kinase mRNA expression, but the protein expression of the eukaryotic initiation factor eIF2 was reduced during HU and restored by ND. Moreover we found an involvement of regenerative pathways, since the increase of MyoD observed after HU suggests the promotion of myogenic stem cell differentiation in response to atrophy. At the same time, Notch-1 expression was down-regulated. Interestingly, the ND treatment prevented changes in MyoD and Notch-1 expression. On the contrary, there was no evidence for an effect of ND on the change of muscle phenotype induced by HU, since no effect of treatment was observed on the resting gCl, restCa and contractile properties in Sol muscle. Accordingly, PGC1α and myosin heavy chain expression, indexes of the phenotype transition, were not restored in ND-treated HU mice. We hypothesize that ND is unable to directly affect the phenotype transition when the specialized motor unit firing pattern of stimulation is lacking. Nevertheless, through stimulation of protein synthesis, ND preserves protein content and muscle weight, which may result advantageous to the affected skeletal muscle for functional recovery.

  13. The Drosophila melanogaster CHD1 chromatin remodeling factor modulates global chromosome structure and counteracts HP1a and H3K9me2.

    Science.gov (United States)

    Bugga, Lakshmi; McDaniel, Ivy E; Engie, Liana; Armstrong, Jennifer A

    2013-01-01

    CHD1 is a conserved chromatin remodeling factor that localizes to active genes and functions in nucleosome assembly and positioning as well as histone turnover. Mouse CHD1 is required for the maintenance of stem cell pluripotency while human CHD1 may function as a tumor suppressor. To investigate the action of CHD1 on higher order chromatin structure in differentiated cells, we examined the consequences of loss of CHD1 and over-expression of CHD1 on polytene chromosomes from salivary glands of third instar Drosophila melanogaster larvae. We observed that chromosome structure is sensitive to the amount of this remodeler. Loss of CHD1 resulted in alterations of chromosome structure and an increase in the heterochromatin protein HP1a, while over-expression of CHD1 disrupted higher order chromatin structure and caused a decrease in levels of HP1a. Over-expression of an ATPase inactive form of CHD1 did not result in severe chromosomal defects, suggesting that the ATPase activity is required for this in vivo phenotype. Interestingly, changes in CHD1 protein levels did not correlate with changes in the levels of the euchromatin mark H3K4me3 or elongating RNA Polymerase II. Thus, while CHD1 is localized to transcriptionally active regions of the genome, it can function to alter the levels of HP1a, perhaps through changes in methylation of H3K9.

  14. The Drosophila melanogaster CHD1 chromatin remodeling factor modulates global chromosome structure and counteracts HP1a and H3K9me2.

    Directory of Open Access Journals (Sweden)

    Lakshmi Bugga

    Full Text Available CHD1 is a conserved chromatin remodeling factor that localizes to active genes and functions in nucleosome assembly and positioning as well as histone turnover. Mouse CHD1 is required for the maintenance of stem cell pluripotency while human CHD1 may function as a tumor suppressor. To investigate the action of CHD1 on higher order chromatin structure in differentiated cells, we examined the consequences of loss of CHD1 and over-expression of CHD1 on polytene chromosomes from salivary glands of third instar Drosophila melanogaster larvae. We observed that chromosome structure is sensitive to the amount of this remodeler. Loss of CHD1 resulted in alterations of chromosome structure and an increase in the heterochromatin protein HP1a, while over-expression of CHD1 disrupted higher order chromatin structure and caused a decrease in levels of HP1a. Over-expression of an ATPase inactive form of CHD1 did not result in severe chromosomal defects, suggesting that the ATPase activity is required for this in vivo phenotype. Interestingly, changes in CHD1 protein levels did not correlate with changes in the levels of the euchromatin mark H3K4me3 or elongating RNA Polymerase II. Thus, while CHD1 is localized to transcriptionally active regions of the genome, it can function to alter the levels of HP1a, perhaps through changes in methylation of H3K9.

  15. High level of Bcl-2 counteracts apoptosis mediated by a live rabies virus vaccine strain and induces long-term infection

    International Nuclear Information System (INIS)

    Thoulouze, Maria-Isabel; Lafage, Mireille; Yuste, Victor J.; Baloul, Leiela; Edelman, Lena; Kroemer, Guido; Israel, Nicole; Susin, Santos A.; Lafon, Monique

    2003-01-01

    We report here that rabies virus strains, currently used to immunize wildlife against rabies, induce not only caspase-dependent apoptosis in the human lymphoblastoid Jurkat T cell line (Jurkat-vect), but also a caspase-independent pathway involving the apoptosis-inducing factor (AIF). In contrast, a strain of neurotropic RV that does not induce apoptosis did not activate caspases or induce AIF translocation. Bcl-2 overproduction in Jurkat T cells (Jurkat-Bcl-2) abolished both pathways. ERA infection and production were similar in Jurkat-vect and Jurkat-Bcl-2 cells, indicating Bcl-2 has no direct antiviral effects. Bcl-2 production is naturally upregulated by day 3 in ERA-infected Jurkat-vect cultures. The increase in Bcl-2 levels seems to be controlled by the virus infection itself and results in the establishment of long-term, persistently infected cultures that continue to produce virus. Thus, in infections with live RV vaccine strains, infected cells may be productive reservoirs of virus in the long term. This may account for the high efficacy of live rabies vaccines

  16. Review on Mycotoxin Issues in Ruminants: Occurrence in Forages, Effects of Mycotoxin Ingestion on Health Status and Animal Performance and Practical Strategies to Counteract Their Negative Effects

    Directory of Open Access Journals (Sweden)

    Antonio Gallo

    2015-08-01

    Full Text Available Ruminant diets include cereals, protein feeds, their by-products as well as hay and grass, grass/legume, whole-crop maize, small grain or sorghum silages. Furthermore, ruminants are annually or seasonally fed with grazed forage in many parts of the World. All these forages could be contaminated by several exometabolites of mycotoxigenic fungi that increase and diversify the risk of mycotoxin exposure in ruminants compared to swine and poultry that have less varied diets. Evidence suggests the greatest exposure for ruminants to some regulated mycotoxins (aflatoxins, trichothecenes, ochratoxin A, fumonisins and zearalenone and to many other secondary metabolites produced by different species of Alternaria spp. (e.g., AAL toxins, alternariols, tenuazonic acid or 4Z-infectopyrone, Aspergillus flavus (e.g., kojic acid, cyclopiazonic acid or β-nitropropionic acid, Aspergillus fuminatus (e.g., gliotoxin, agroclavine, festuclavines or fumagillin, Penicillium roqueforti and P. paneum (e.g., mycophenolic acid, roquefortines, PR toxin or marcfortines or Monascus ruber (citrinin and monacolins could be mainly related to forage contamination. This review includes the knowledge of mycotoxin occurrence reported in the last 15 years, with special emphasis on mycotoxins detected in forages, and animal toxicological issues due to their ingestion. Strategies for preventing the problem of mycotoxin feed contamination under farm conditions are discussed.

  17. Review on Mycotoxin Issues in Ruminants: Occurrence in Forages, Effects of Mycotoxin Ingestion on Health Status and Animal Performance and Practical Strategies to Counteract Their Negative Effects.

    Science.gov (United States)

    Gallo, Antonio; Giuberti, Gianluca; Frisvad, Jens C; Bertuzzi, Terenzio; Nielsen, Kristian F

    2015-08-12

    Ruminant diets include cereals, protein feeds, their by-products as well as hay and grass, grass/legume, whole-crop maize, small grain or sorghum silages. Furthermore, ruminants are annually or seasonally fed with grazed forage in many parts of the World. All these forages could be contaminated by several exometabolites of mycotoxigenic fungi that increase and diversify the risk of mycotoxin exposure in ruminants compared to swine and poultry that have less varied diets. Evidence suggests the greatest exposure for ruminants to some regulated mycotoxins (aflatoxins, trichothecenes, ochratoxin A, fumonisins and zearalenone) and to many other secondary metabolites produced by different species of Alternaria spp. (e.g., AAL toxins, alternariols, tenuazonic acid or 4Z-infectopyrone), Aspergillus flavus (e.g., kojic acid, cyclopiazonic acid or β-nitropropionic acid), Aspergillus fuminatus (e.g., gliotoxin, agroclavine, festuclavines or fumagillin), Penicillium roqueforti and P. paneum (e.g., mycophenolic acid, roquefortines, PR toxin or marcfortines) or Monascus ruber (citrinin and monacolins) could be mainly related to forage contamination. This review includes the knowledge of mycotoxin occurrence reported in the last 15 years, with special emphasis on mycotoxins detected in forages, and animal toxicological issues due to their ingestion. Strategies for preventing the problem of mycotoxin feed contamination under farm conditions are discussed.

  18. Review on Mycotoxin Issues in Ruminants: Occurrence in Forages, Effects of Mycotoxin Ingestion on Health Status and Animal Performance and Practical Strategies to Counteract Their Negative Effects

    Science.gov (United States)

    Gallo, Antonio; Giuberti, Gianluca; Frisvad, Jens C.; Bertuzzi, Terenzio; Nielsen, Kristian F.

    2015-01-01

    Ruminant diets include cereals, protein feeds, their by-products as well as hay and grass, grass/legume, whole-crop maize, small grain or sorghum silages. Furthermore, ruminants are annually or seasonally fed with grazed forage in many parts of the World. All these forages could be contaminated by several exometabolites of mycotoxigenic fungi that increase and diversify the risk of mycotoxin exposure in ruminants compared to swine and poultry that have less varied diets. Evidence suggests the greatest exposure for ruminants to some regulated mycotoxins (aflatoxins, trichothecenes, ochratoxin A, fumonisins and zearalenone) and to many other secondary metabolites produced by different species of Alternaria spp. (e.g., AAL toxins, alternariols, tenuazonic acid or 4Z-infectopyrone), Aspergillus flavus (e.g., kojic acid, cyclopiazonic acid or β-nitropropionic acid), Aspergillus fuminatus (e.g., gliotoxin, agroclavine, festuclavines or fumagillin), Penicillium roqueforti and P. paneum (e.g., mycophenolic acid, roquefortines, PR toxin or marcfortines) or Monascus ruber (citrinin and monacolins) could be mainly related to forage contamination. This review includes the knowledge of mycotoxin occurrence reported in the last 15 years, with special emphasis on mycotoxins detected in forages, and animal toxicological issues due to their ingestion. Strategies for preventing the problem of mycotoxin feed contamination under farm conditions are discussed. PMID:26274974

  19. Methyl jasmonate counteracts boron toxicity by preventing oxidative stress and regulating antioxidant enzyme activities and artemisinin biosynthesis in Artemisia annua L.

    Science.gov (United States)

    Aftab, Tariq; Khan, M Masroor A; Idrees, Mohd; Naeem, M; Moinuddin; Hashmi, Nadeem

    2011-07-01

    Boron is an essential plant micronutrient, but it is phytotoxic if present in excessive amounts in soil for certain plants such as Artemisia annua L. that contains artemisinin (an important antimalarial drug) in its areal parts. Artemisinin is a sesquiterpene lactone with an endoperoxide bridge. It is quite expensive compound because the only commercial source available is A. annua and the compound present in the plant is in very low concentration. Since A. annua is a major source of the antimalarial drug and B stress is a deadly threat to its cultivation, the present research was conducted to determine whether the exogenous application of methyl jasmonate (MeJA) could combat the ill effects of excessive B present in the soil. According to the results obtained, the B toxicity induced oxidative stress and reduced the stem height as well as fresh and dry masses of the plant remarkably. The excessive amounts of soil B also lowered the net photosynthetic rate, stomatal conductance, internal CO(2) concentration and total chlorophyll content in the leaves. In contrast, the foliar application of MeJA enhanced the growth and photosynthetic efficiency both in the stressed and non-stressed plants. The excessive B levels also increased the activities of antioxidant enzymes, such as catalase, peroxidase and superoxide dismutase. Endogenous H(2)O(2) and O(2)(-) levels were also high in the stressed plants. However, the MeJA application to the stressed plants reduced the amount of lipid peroxidation and stimulated the synthesis of antioxidant enzymes, enhancing the content and yield of artemisinin as well. Thus, it was concluded that MeJA might be utilized in mitigating the B toxicity and improving the content and yield of artemisinin in A. annua plant.

  20. The ability of H1 or H2 receptor antagonists or their combination in counteracting the glucocorticoid-induced alveolar bone loss in rats.

    Science.gov (United States)

    Ezzat, Bassant A; Abbass, Marwa M S

    2014-02-01

    The aim of the present study was to compare between three possible osteoporotic treatments in prevention of glucocorticoid-induced alveolar bone loss. Fifty adult female Wistar rats with an average weight 150-200 g were randomized into five groups: group I (control) was intraperitoneally injected with saline. The other experimental groups (II & III, IV & V) were intraperitoneally injected with 200 µg/100 g body weight dexamethasone. The experimental groups III, IV and V received intraperitoneal injection of 10 mg/kg/day pheniramine maleate (H1 receptor antagonist), ranitidine hydrochloride (H2 receptor antagonist) and concomitant doses of both H1 & H2 receptor antagonists respectively. After 30 days, the rats have been sacrificed. The mandibles were examined histologically, histochemically and histomorphometrically. The bone mineral density was measured using dual-energy X-ray absorptiometry (DEXA). Histopathologically the glucocorticoid group showed wide medullary cavities with wide osteocytic lacunae. These marrow cavities were reduced in the prophylactic groups (III, IV) but increased in group V. Bone histomorphometric analysis revealed improvement in static bone parameters in groups III and IV and deterioration in group V in comparison to group II. The DEXA revealed significant reduction in the bone mineral density in all experimental groups compared to the control group. In a rat model, the administration of H1 or H2 receptor antagonists separately could minimize the alveolar bone loss caused by the administration of glucocorticoids while concomitant administration of both H1 and H2 receptor antagonists deteriorated the bone condition. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. The loss of function of PhaC1 is a survival mechanism that counteracts the stress caused by the overproduction of poly-3-hydroxyalkanoates in Pseudomonas putidaΔfadBA.

    Science.gov (United States)

    Obeso, José I; Maestro, Beatriz; Sanz, Jesús M; Olivera, Elías R; Luengo, José M

    2015-09-01

    The poly-3-hydroxylkanoate (PHA)-overproducing mutant Pseudomonas putida U ΔfadBA (PpΔfadBA) lacks the genes encoding the main β-oxidation pathway (FadBA). This strain accumulates enormous amounts of bioplastics when cultured in chemically defined media containing PHA precursors (different n-alkanoic or n-aryl-alkanoic acids) and an additional carbon source. In medium containing glucose or 4-hydroxy-phenylacetate, the mutant does not accumulate PHAs and grows just as the wild type (P. putida U). However, when the carbon source is octanoate, growth is severely impaired, suggesting that in PpΔfadBA, the metabolic imbalance resulting from a lower rate of β-oxidation, together with the accumulation of bioplastics, causes severe physiological stress. Here, we show that PpΔfadBA efficiently counteracts this latter effect via a survival mechanism involving the introduction of spontaneous mutations that block PHA accumulation. Surprisingly, genetic analyses of the whole pha cluster revealed that these mutations occurred only in the gene encoding one of the polymerases (phaC1) and that the loss of PhaC1 function was enough to prevent PHA synthesis. The influence of these mutations on the structure of PhaC1 and the existence of a protein-protein (PhaC1-PhaC2) interaction that explains the functionality of the polymerization system are discussed herein. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

  2. cAMP-secretion coupling is impaired in diabetic GK/Par rat β-cells: a defect counteracted by GLP-1.

    Science.gov (United States)

    Dolz, Manuel; Movassat, Jamileh; Bailbé, Danielle; Le Stunff, Hervé; Giroix, Marie-Hélène; Fradet, Magali; Kergoat, Micheline; Portha, Bernard

    2011-11-01

    cAMP-raising agents with glucagon-like peptide-1 (GLP-1) as the first in class, exhibit multiple actions that are beneficial for the treatment of type 2 diabetic (T2D) patients, including improvement of glucose-induced insulin secretion (GIIS). To gain additional insight into the role of cAMP in the disturbed stimulus-secretion coupling within the diabetic β-cell, we examined more thoroughly the relationship between changes in islet cAMP concentration and insulin release in the GK/Par rat model of T2D. Basal cAMP content in GK/Par islets was significantly higher, whereas their basal insulin release was not significantly different from that of Wistar (W) islets. Even in the presence of IBMX or GLP-1, their insulin release did not significantly change despite further enhanced cAMP accumulation in both cases. The high basal cAMP level most likely reflects an increased cAMP generation in GK/Par compared with W islets since 1) forskolin dose-dependently induced an exaggerated cAMP accumulation; 2) adenylyl cyclase (AC)2, AC3, and G(s)α proteins were overexpressed; 3) IBMX-activated cAMP accumulation was less efficient and PDE-3B and PDE-1C mRNA were decreased. Moreover, the GK/Par insulin release apparatus appears less sensitive to cAMP, since GK/Par islets released less insulin at submaximal cAMP levels and required five times more cAMP to reach a maximal secretion rate no longer different from W. GLP-1 was able to reactivate GK/Par insulin secretion so that GIIS became indistinguishable from that of W. The exaggerated cAMP production is instrumental, since GLP-1-induced GIIS reactivation was lost in the presence the AC blocker 2',5'-dideoxyadenosine. This GLP-1 effect takes place in the absence of any improvement of the [Ca(2+)](i) response and correlates with activation of the cAMP-dependent PKA-dependent pathway.

  3. Increasing Public Expenditure

    Directory of Open Access Journals (Sweden)

    Ammar Ben Zaed

    2017-04-01

    Full Text Available This article aims to analyze and interpret the phenomenon of increased public expenditures and test explanatory theories as well as to analyze Abstract the relationship between public spending and GDP in the short and long term where you see the Wagner hypothesis that causal heading of GDP to government spending while there is a causal relationship analysis positive trending of government spending to GDP according to the Keynesian hypothesis in this study will be used descriptive analytical method to validate these hypotheses. Results in the short and long term made it clear that there is a difference in the outcome of Applied Studies where we find that each supports a relationship Wagner in the sense that the causal trending of real GDP to government spending and more precisely to increase the economic growth lead to increased aggregate demand which leads in turn increasing the need to increase government spending and to increase the resources available to the government sector to finance the increase in spending by the additional resources resulting from the economic growth while others opines opposes the existence of the relationship.

  4. Increasing income inequality

    DEFF Research Database (Denmark)

    Frederiksen, Anders; Poulsen, Odile

    In recent decades most developed countries have experienced an increase in income inequality. In this paper, we use an equilibrium search framework to shed additional light on what is causing an income distribution to change. The major benefit of the model is that it can accommodate shocks...... that shocks to the employees' relative productivity, i.e., skill-biased technological change, are unlikely to have caused the increase in income inequality....

  5. Meeting increased demand.

    Science.gov (United States)

    Blair, Andrew

    2004-07-01

    New Zealand is a little country with a little economy but with a population that's rapidly aging. New Zealand's population is only 4.3 million people. It's GDP is only $US58.6 billion (2002). New Zealand's expenditure on health as a percentage of GDP is not out of line with that of other countries. As a nation we have been increasing expenditure on health over recent years. In 1990 we spent 7% of GDP on health. In 1995 that increased to 7.65% and is now 8.3%. However, in per capita terms our expenditure on health does not compare so well with like countries. The size of New Zealand's economy is restricting what our country spends on health. Health is already the second highest demand on the New Zealand tax dollar. The tolerance of New Zealanders would be challenged if a Government attempted to increase taxes further to meet the growing demands for expenditure on health, but at the same time the population's expectations are increasing. This is the challenging situation we face today. What lies ahead? Like all industrialized countries New Zealand is facing an aging population. The population below age 40 is decreasing, but it is increasing significantly over that age. 16% of the population is currently aged over 60. By 2051 this proportion will almost double to just over 31%. Coupled with the aging population is increased awareness and expectations, as access to options for treatment and technology becomes readily accessible to the population through such media as the internet. The extent of the impact of the aging population can be clearly represented by focusing on one specialty such as orthopaedics. The New Zealand Orthopaecic Association undertook a study in July 2003 which concluded (among other things) that as a result of the projected aging of the population, over the next 50 years: Musculo-skeletal operations will increase by over 30%. The number of hip replacements will nearly double. The incidence of osteoporosis will increase by a massive 201%. The number

  6. Increased urinary orosomucoid excretion

    DEFF Research Database (Denmark)

    Christiansen, M S; Iversen, K; Larsen, C T

    2009-01-01

    , impaired left ventricular function and endothelial dysfunction in patients with type 2 diabetes. MATERIAL AND METHODS: We performed a cross-sectional study of 41 patients with type 2 diabetes (17 patients with normal UOER and 24 with increased UOER) with no history of cardiovascular disease and 21 healthy...

  7. Integrated engineering increases flexibility

    International Nuclear Information System (INIS)

    Smith, Ray

    1991-01-01

    Integrated Engineering (IE) can be used to describe the best use of increasingly rare good engineering talent in an increasingly competive world. A number of organisations are now moving towards IE without any general agreement on a precise definition. The engineering division of British Nuclear Fuels (BNFL) is one such organisation. This feature covers the reasoning behind the decision, and our experience to date. BNFL engineering division is responsible primarily for the provision of major facilities on BNFL operational sites. This provision includes feasibility, front end and detailed design, procurement, installation and commissioning. Task force working has been used for some of the large projects. But the future workload is expected to comprise many more smaller projects. At the same time, equipment is becoming more complex and the need for mutual understanding and appreciation between disciplines is increasing. To meet this increasing need for flexibility, BNFL has decided to move to the matrix structure of project management and functional departments described in the article. (Author)

  8. Applied means to increase stimulation in the control room work at the Swedish nuclear power plants

    International Nuclear Information System (INIS)

    Blomberg, P.E.; Akerhielm, F.

    1988-01-01

    Nuclear power plants are generally designed and built with a quality which implies that the units seldom require intervention from the operating staff under normal operating conditions. This leaves the operators with the dominating task of only passively supervising the process. A number of measures have been taken to counteract the problem of under-stimulated individuals in the control rooms and to maintain active and purposeful working conditions. Basically these measures derive from the belief that augmented competence, increased responsibilities and a enhanced sense of indispensability functions as an inspiration even in a monotonous working situation. For this purpose a number of activities and tasks, parallel to the normal duties as member of the operating staff, have been implemented

  9. Counteracting Power Analysis Attacks by Masking

    Science.gov (United States)

    Oswald, Elisabeth; Mangard, Stefan

    The publication of power analysis attacks [12] has triggered a lot of research activities. On the one hand these activities have been dedicated toward the development of secure and efficient countermeasures. On the other hand also new and improved attacks have been developed. In fact, there has been a continuous arms race between designers of countermeasures and attackers. This chapter provides a brief overview of the state-of-the art in the arms race in the context of a countermeasure called masking. Masking is a popular countermeasure that has been extensively discussed in the scientific community. Numerous articles have been published that explain different types of masking and that analyze weaknesses of this countermeasure.

  10. Counteracting Misconceptions About the Socratic Method.

    Science.gov (United States)

    Fishman, Ethan M.

    1985-01-01

    The Socratic method, while utilizing student participation, emphasizes self-knowledge, not self-expression. This is accomplished on the basis of successive stages of issue analysis and self-examination. The Socratic method strives to get at the root of belief by studying assumptions. (MLW)

  11. High population increase rates.

    Science.gov (United States)

    1991-09-01

    In addition to its economic and ethnic difficulties, the USSR faces several pressing demographic problems, including high population increase rates in several of its constituent republics. It has now become clear that although the country's rigid centralized planning succeeded in covering the basic needs of people, it did not lead to welfare growth. Since the 1970s, the Soviet economy has remained sluggish, which as led to increase in the death and birth rates. Furthermore, the ideology that held that demography could be entirely controlled by the country's political and economic system is contradicted by current Soviet reality, which shows that religion and ethnicity also play a significant role in demographic dynamics. Currently, Soviet republics fall under 2 categories--areas with high or low natural population increase rates. Republics with low rates consist of Christian populations (Armenia, Moldavia, Georgia, Byelorussia, Russia, Lithuania, Estonia, Latvia, Ukraine), while republics with high rates are Muslim (Tadzhikistan, Uzbekistan, Turkmenistan, Kirgizia, Azerbaijan Kazakhstan). The later group has natural increase rates as high as 3.3%. Although the USSR as a whole is not considered a developing country, the later group of republics fit the description of the UNFPA's priority list. Another serious demographic issue facing the USSR is its extremely high rate of abortion. This is especially true in the republics of low birth rates, where up to 60% of all pregnancies are terminated by induced abortions. Up to 1/5 of the USSR's annual health care budget is spent on clinical abortions -- money which could be better spent on the production of contraceptives. Along with the recent political and economic changes, the USSR is now eager to deal with its demographic problems.

  12. Effect of acetyl salicylic acid on increased production of thromboxane after aortic graft surgery.

    Science.gov (United States)

    Lewin, J; Swedenborg, J; Egberg, N; Vesterqvist, O; Green, K

    1989-06-01

    Contact between blood and foreign surfaces, e.g. vascular grafts, causes activation and release of platelets. One consequence of platelet activation is production of thromboxane A2 (TxA2). The physiological effects of TxA2, i.e. platelet aggregation and vaso-constriction are counteracted by another prostanoid, prostacyclin (PGI2). Acetylsalicylic acid (ASA) causes a longlasting inhibition of platelet TxA2 production and a more shortlasting inhibition of PGI2 production. The present study examines TxA2 and PGI2 synthesis in patients receiving synthetic arterial grafts, some of which were treated with ASA. The prostanoid synthesis was evaluated by measurement of their main urinary metabolites with gas chromatography-mass spectrometry. Platelet release was evaluated by measurements of beta-thromboglobulin (beta-TG) and the plasma coagulation by measurements of fibrinopeptide A (FPA). These compounds were also measured in urine in order to avoid artifacts caused by activation of platelets and plasma coagulation during blood sampling. Following replacement of the abdominal aorta with a synthetic vascular graft there was a marked increase in the synthesis of TxA2 and PGI2. Increased levels of beta-TG and FPA were also demonstrated. Administration of ASA on the first and second postoperative days significantly reduced the synthesis of TxA2 but caused no significant effects on the other parameters measured. It is concluded that ASA may be beneficial in the postoperative period since it counteracts TxA2 with vasoconstricting and platelet aggregating properties but leaves PGI2 with vasodilating and antiaggregating properties relatively uneffected.

  13. Violencia y contrapoder: una ventana al mundo de las mujeres indígenas migrantes, en México Violence and means to counteract power: a view to migrant indigenous women in Mexico

    Directory of Open Access Journals (Sweden)

    Sara María Lara Flores

    2003-12-01

    Full Text Available El artículo analiza las condiciones en las que las mujeres se incorporan al sector agrícola de exportación en México. Este sector genera una fuerte demanda de mano de obra en el nivel nacional, lo cual ocasiona importantes flujos de migración en los que algunas indígenas participan de manera significativa. El artículo muestra cómo dicha incorporación de mano de obra femenina al mercado de trabajo pone en juego desigualdades de género y étnicas que se traducen en una segmentación dentro de las ramas y sectores de la economía. Asimismo, el estudio describe los procesos a que recurren las indígenas con el fin de contrarrestar la violencia real y simbólica de que son objeto.The article analizes the conditions in which women farmers incorporate into México’s exports processes. This sector has a great need of labour at the national level, which in turn brings about many migration fluxes in which indigenous women play an important role. The study shows how this feminine incorporation into the labour market triggers gender as well as ethnic inequalities that manifest themselves in a segmentation within the branches and sectors of the national economy. Also, the article describes the means to which indigenous women turn to in order to counteract the actual and symbolic violence they are submitted to.

  14. Cesarean sections in Brazil: will they ever stop increasing?

    Directory of Open Access Journals (Sweden)

    Fernando C. Barros

    Full Text Available OBJECTIVE: To describe trends, geographic distribution, and risk factors for cesarean deliveries in Brazil in 2000-2011, and to determine if efforts to curtail rates have had a measurable impact. METHODS: This was an observational study using nationwide information from the Department of Informatics of the Unified Health System (DATASUS. Individual level analyses were based on data regarding maternal education, age, parity, and skin color. Ecological analyses at the level of 431 health districts investigated the relationships with health facility density and poverty level. RESULTS: Cesarean rates increased markedly, from 37.9% in 2000 to 53.9% in 2011. Preliminary results from 2012 showed a rate of 55.8%, with the richest geographic areas showing the highest rates. Rates at the municipal level varied from 9%-96%. Cesareans were more common in women with higher education, white skin color, older age, and in primi- paras. In the ecological analyses, the number of health facilities per 1 000 population was strongly and positively correlated with cesarean rates, with an increase of 16.1 percentage points (95% Confidence Interval [95%CI] = 4.3-17.8 for each facility. An increase of 1 percentage point in the poverty rate was associated with a decline of 0.5 percentage point in cesarean rates (95%CI = 0.5-0.6. CONCLUSIONS: The strong associations with maternal education and health facility density suggest that the vast majority of cesareans are not medically indicated. A number of policies and programs have been launched to counteract this trend, but have had virtually no impact.

  15. Global Increases in Individualism.

    Science.gov (United States)

    Santos, Henri C; Varnum, Michael E W; Grossmann, Igor

    2017-09-01

    Individualism appears to have increased over the past several decades, yet most research documenting this shift has been limited to the study of a handful of highly developed countries. Is the world becoming more individualist as a whole? If so, why? To answer these questions, we examined 51 years of data on individualist practices and values across 78 countries. Our findings suggest that individualism is indeed rising in most of the societies we tested. Despite dramatic shifts toward greater individualism around the world, however, cultural differences remain sizable. Moreover, cultural differences are primarily linked to changes in socioeconomic development, and to a lesser extent to shifts in pathogen prevalence and disaster frequency.

  16. ORIC Beam Energy Increase

    CERN Document Server

    Mallory, Merrit L; Dowling, Darryl; Hudson, Ed; Lord, Dick; Tatum, Alan

    2005-01-01

    The detection of and solution to a beam interference problem in the Oak Ridge Isochronous Cyclotron (ORIC) extraction system has yielded a 20% increase in the proton beam energy. The beam from ORIC was designed to be extracted before the nu r equal one resonance. Most cyclotrons extract after the nu r equal one resonance, thus getting more usage of the magnetic field for energy acceleration. We have now determined that the electrostatic deflector septum interferes with the last accelerated orbit in ORIC, with the highest extraction efficiency obtained near the maximum nu r value. This nu r provides a rotation in the betatron oscillation amplitude that is about the same length as the electrostatic septum thus allowing the beam to jump over the interference problem with the septum. With a thinned septum we were able to tune the beam through the nu r equal one resonance and achieve a 20% increase in beam energy. This nu r greater than one extraction method may be desirable for very high field cyclotrons since it...

  17. Gas revenue increasingly significant

    International Nuclear Information System (INIS)

    Megill, R.E.

    1991-01-01

    This paper briefly describes the wellhead prices of natural gas compared to crude oil over the past 70 years. Although natural gas prices have never reached price parity with crude oil, the relative value of a gas BTU has been increasing. It is one of the reasons that the total amount of money coming from natural gas wells is becoming more significant. From 1920 to 1955 the revenue at the wellhead for natural gas was only about 10% of the money received by producers. Most of the money needed for exploration, development, and production came from crude oil. At present, however, over 40% of the money from the upstream portion of the petroleum industry is from natural gas. As a result, in a few short years natural gas may become 50% of the money revenues generated from wellhead production facilities

  18. Increased evaporation following widespread tree mortality limits streamflow response

    Science.gov (United States)

    Biederman, J. A.; Harpold, A. A.; Gochis, D. J.; Ewers, B. E.; Reed, D. E.; Papuga, S. A.; Brooks, P. D.

    2014-07-01

    A North American epidemic of mountain pine beetle (MPB) has disturbed over 5 million ha of forest containing headwater catchments crucial to water resources. However, there are limited observations of MPB effects on partitioning of precipitation between vapor loss and streamflow, and to our knowledge these fluxes have not been observed simultaneously following disturbance. We combined eddy covariance vapor loss (V), catchment streamflow (Q), and stable isotope indicators of evaporation (E) to quantify hydrologic partitioning over 3 years in MPB-impacted and control sites. Annual control V was conservative, varying only from 573 to 623 mm, while MPB site V varied more widely from 570 to 700 mm. During wet periods, MPB site V was greater than control V in spite of similar above-canopy potential evapotranspiration (PET). During a wet year, annual MPB V was greater and annual Q was lower as compared to an average year, while in a dry year, essentially all water was partitioned to V. Ratios of 2H and 18O in stream and soil water showed no kinetic evaporation at the control site, while MPB isotope ratios fell below the local meteoric water line, indicating greater E and snowpack sublimation (Ss) counteracted reductions in transpiration (T) and sublimation of canopy-intercepted snow (Sc). Increased E was possibly driven by reduced canopy shading of shortwave radiation, which averaged 21 W m-2 during summer under control forest as compared to 66 W m-2 under MPB forest. These results show that abiotic vapor losses may limit widely expected streamflow increases.

  19. The inhibition of assembly of HIV-1 virus-like particles by 3-O-(3',3'-dimethylsuccinyl betulinic acid (DSB is counteracted by Vif and requires its Zinc-binding domain

    Directory of Open Access Journals (Sweden)

    Bouaziz Serge

    2008-12-01

    Full Text Available Abstract Background DSB, the 3-O-(3',3'dimethylsuccinyl derivative of betulinic acid, blocks the last step of protease-mediated processing of HIV-1 Gag precursor (Pr55Gag, which leads to immature, noninfectious virions. When administered to Pr55Gag-expressing insect cells (Sf9, DSB inhibits the assembly and budding of membrane-enveloped virus-like particles (VLP. In order to explore the possibility that viral factors could modulate the susceptibility to DSB of the VLP assembly process, several viral proteins were coexpressed individually with Pr55Gag in DSB-treated cells, and VLP yields assayed in the extracellular medium. Results Wild-type Vif (Vifwt restored the VLP production in DSB-treated cells to levels observed in control, untreated cells. DSB-counteracting effect was also observed with Vif mutants defective in encapsidation into VLP, suggesting that packaging and anti-DSB effect were separate functions in Vif. The anti-DSB effect was abolished for VifC133S and VifS116V, two mutants which lacked the zinc binding domain (ZBD formed by the four H108C114C133H139 coordinates with a Zn atom. Electron microscopic analysis of cells coexpressing Pr55Gag and Vifwt showed that a large proportion of VLP budded into cytoplasmic vesicles and were released from Sf9 cells by exocytosis. However, in the presence of mutant VifC133S or VifS116V, most of the VLP assembled and budded at the plasma membrane, as in control cells expressing Pr55Gag alone. Conclusion The function of HIV-1 Vif protein which negated the DSB inhibition of VLP assembly was independent of its packaging capability, but depended on the integrity of ZBD. In the presence of Vifwt, but not with ZBD mutants VifC133S and VifS116V, VLP were redirected to a vesicular compartment and egressed via the exocytic pathway.

  20. Increasing paternal responsibility.

    Science.gov (United States)

    Cutright, P

    1985-01-01

    Increasing numbers of fathers of children born out of wedlock are not contributing to these children's economic support. In 1981, a tiny minority (14%) of the 1.7 million never-married mothers living with a child with an absent father had a child-support award, and of these, just 112,000 actually received some payment in 1981. The high rates of noncompliance, and the low level of legal efforts to enforce child support, are the result of attempts to collect payments through inefficient traditional methods, not the inability of fathers to pay, a Wisconsin study has shown. A basic problem with collecting child support under the present system is that it relies on fathers to control their expenditures and voluntarily to send the payment on a weekly, biweekly or monthly basis, year after year. As a Wisconsin study shows, full compliance with court-ordered payments dropped from 38% in the 1st year to below 20% by the 5th year among 163 ex-husbands tracked. A proposal by researchers at the University of Wisconsin's Institute for Research on Poverty calls for an "absent-parent tax." The Wisconsin Plan, as it is known, is simply a withholding tax based on the father's gross income and the number of his absent children. If his income falls below a certain level, payments will stop automatically, but will resume if and when it rises above the cutoff point. The Wisconsin plan removes all judicial discretion and lawyer's skill as factors in child-support awards, thus eliminating erratic awards. It also insures that support payments will be maintained during periods of conflict between the father and mother. However, before the Wisconsin Plan can effectively protect children both out of wedlock, a feature needs to be added that will establish paternity at birth. Imposing a real child-support obligation on fathers of children born outside of marriage will introduce a potentially powerful economic incentive for responsible male reproductive and parental behavior.

  1. Trapezius muscle activity increases during near work activity regardless of accommodation/vergence demand level.

    Science.gov (United States)

    Richter, H O; Zetterberg, C; Forsman, M

    2015-07-01

    To investigate if trapezius muscle activity increases over time during visually demanding near work. The vision task consisted of sustained focusing on a contrast-varying black and white Gabor grating. Sixty-six participants with a median age of 38 (range 19-47) fixated the grating from a distance of 65 cm (1.5 D) during four counterbalanced 7-min periods: binocularly through -3.5 D lenses, and monocularly through -3.5 D, 0 D and +3.5 D. Accommodation, heart rate variability and trapezius muscle activity were recorded in parallel. General estimating equation analyses showed that trapezius muscle activity increased significantly over time in all four lens conditions. A concurrent effect of accommodation response on trapezius muscle activity was observed with the minus lenses irrespective of whether incongruence between accommodation and convergence was present or not. Trapezius muscle activity increased significantly over time during the near work task. The increase in muscle activity over time may be caused by an increased need of mental effort and visual attention to maintain performance during the visual tasks to counteract mental fatigue.

  2. Chronic central administration of Ghrelin increases bone mass through a mechanism independent of appetite regulation.

    Directory of Open Access Journals (Sweden)

    Hyung Jin Choi

    Full Text Available Leptin plays a critical role in the central regulation of bone mass. Ghrelin counteracts leptin. In this study, we investigated the effect of chronic intracerebroventricular administration of ghrelin on bone mass in Sprague-Dawley rats (1.5 μg/day for 21 days. Rats were divided into control, ghrelin ad libitum-fed (ghrelin ad lib-fed, and ghrelin pair-fed groups. Ghrelin intracerebroventricular infusion significantly increased body weight in ghrelin ad lib-fed rats but not in ghrelin pair-fed rats, as compared with control rats. Chronic intracerebroventricular ghrelin infusion significantly increased bone mass in the ghrelin pair-fed group compared with control as indicated by increased bone volume percentage, trabecular thickness, trabecular number and volumetric bone mineral density in tibia trabecular bone. There was no significant difference in trabecular bone mass between the control group and the ghrelin ad-lib fed group. Chronic intracerebroventricular ghrelin infusion significantly increased the mineral apposition rate in the ghrelin pair-fed group as compared with control. In conclusion, chronic central administration of ghrelin increases bone mass through a mechanism that is independent of body weight, suggesting that ghrelin may have a bone anabolic effect through the central nervous system.

  3. Potassium and zinc increase tolerance to salt stress in wheat (Triticum aestivum L.).

    Science.gov (United States)

    Jan, Amin Ullah; Hadi, Fazal; Midrarullah; Nawaz, Muhammad Asif; Rahman, Khaista

    2017-07-01

    Potassium and zinc are essential elements in plant growth and metabolism and plays a vital role in salt stress tolerance. To investigate the physiological mechanism of salt stress tolerance, a pot experiment was conducted. Potassium and zinc significantly minimize the oxidative stress and increase root, shoot and spike length in wheat varieties. Fresh and dry biomass were significantly increased by potassium followed by zinc as compared to control C. The photosynthetic pigment and osmolyte regulator (proline, total phenolic, and total carbohydrate) were significantly enhanced by potassium and zinc. Salt stress increases MDA content in wheat varieties while potassium and zinc counteract the adverse effect of salinity and significantly increased membrane stability index. Salt stress decreases the activities of antioxidant enzymes (superoxide dismutase, catalase and ascorbate peroxidase) while the exogenous application of potassium and zinc significantly enhanced the activities of these enzymes. A significant positive correlation was found of spike length with proline (R 2  = 0.966 ∗∗∗ ), phenolic (R 2  = 0.741 ∗ ) and chlorophyll (R 2  = 0.853 ∗∗ ). The MDA content showed significant negative correlation (R 2  = 0.983 ∗∗∗ ) with MSI. It is concluded that potassium and zinc reduced toxic effect of salinity while its combine application showed synergetic effect and significantly enhanced salt tolerance. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Zinc can increase the activity of protein kinase C and contributes to its binding to plasma membranes in T lymphocytes

    International Nuclear Information System (INIS)

    Csermely, P.; Szamel, M.; Resch, K.; Somogyi, J.

    1988-01-01

    In the primary structure of protein kinase C, the presence of a putative metal-binding site has been suggested. In the present report, the authors demonstrate that the most abundant intracellular heavy metal, zinc, can increase the activity of cytosolic protein kinase C. Zinc reversibly binds the enzyme to plasma membranes,and it may contribute to the calcium-induced binding as well. The intracellular heavy metal chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine prevents the phorbol ester- and antigen-induced translocation of protein kinase C. This effect can be totally reversed by the concomitant addition of Zn 2+ , while Fe 2+ and Mn 2+ are only partially counteractive. The results suggest that zinc can activate protein kinase C and contributes to its binding to plasma membranes in T lymphocytes induced by Ca 2+ , phorbol ester, or antigen

  5. A weight-loss program adapted to the menstrual cycle increases weight loss in healthy, overweight, premenopausal women

    DEFF Research Database (Denmark)

    Geiker, Nina R W; Ritz, Christian; Pedersen, Sue D

    2016-01-01

    compared with the effect of simple energy restriction. DESIGN: A total of 60 healthy, overweight, premenopausal women were included in a 6-mo weight-loss program in which each subject consumed a diet of 1600 kcal/d. Subjects were randomly assigned to either a combined diet and exercise program...... that was tailored to metabolic changes of the menstrual cycle (Menstralean) or to undergo simple energy restriction (control). RESULTS: Thirty-one women (19 Menstralean and 12 control women) completed the study [mean ± SD body mass index (in kg/m(2)): 32.0 ± 5.2]. Both groups lost weight during the study....... CONCLUSION: A differentiated diet and exercise program that is tailored to counteract food cravings and metabolic changes throughout the menstrual cycle may increase weight loss above that achieved with a traditional diet and exercise program in women who can comply with the program. This trial...

  6. Increasing emitter efficiency in 3.3-kV enhanced trench IGBTs for higher short-circuit capability

    DEFF Research Database (Denmark)

    Reigosa, Paula Diaz; Iannuzzo, Francesco; Rahimo, Munaf

    2018-01-01

    In this paper, a 3.3-kV Enhanced Trench IGBT has been designed with a high emitter efficiency, for improving its short-circuit robustness. The carrier distribution profile has been shaped in a way that it is possible to increase the electric field at the surface of the IGBT, and thereby, counteract...... the Kirk Effect onset. This design approach is beneficial for mitigating high-frequency oscillations, typically observed in IGBTs under short-circuit conditions. The effectiveness of the proposed design rule is validated by means of mixed-mode device simulations. Then, two IGBTs have been fabricated...... with different emitter efficiencies and tested under short circuit, validating that the high-frequency oscillations can be mitigated, with higher emitter efficiency IGBT designs....

  7. Zinc can increase the activity of protein kinase C and contributes to its binding to plasma membranes in T lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Csermely, P.; Szamel, M.; Resch, K.; Somogyi, J.

    1988-05-15

    In the primary structure of protein kinase C, the presence of a putative metal-binding site has been suggested. In the present report, the authors demonstrate that the most abundant intracellular heavy metal, zinc, can increase the activity of cytosolic protein kinase C. Zinc reversibly binds the enzyme to plasma membranes,and it may contribute to the calcium-induced binding as well. The intracellular heavy metal chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine prevents the phorbol ester- and antigen-induced translocation of protein kinase C. This effect can be totally reversed by the concomitant addition of Zn/sup 2 +/, while Fe/sup 2 +/ and Mn/sup 2 +/ are only partially counteractive. The results suggest that zinc can activate protein kinase C and contributes to its binding to plasma membranes in T lymphocytes induced by Ca/sup 2 +/, phorbol ester, or antigen.

  8. Increasing Northern Hemisphere water deficit

    Science.gov (United States)

    McCabe, Gregory J.; Wolock, David M.

    2015-01-01

    A monthly water-balance model is used with CRUTS3.1 gridded monthly precipitation and potential evapotranspiration (PET) data to examine changes in global water deficit (PET minus actual evapotranspiration) for the Northern Hemisphere (NH) for the years 1905 through 2009. Results show that NH deficit increased dramatically near the year 2000 during both the cool (October through March) and warm (April through September) seasons. The increase in water deficit near 2000 coincides with a substantial increase in NH temperature and PET. The most pronounced increases in deficit occurred for the latitudinal band from 0 to 40°N. These results indicate that global warming has increased the water deficit in the NH and that the increase since 2000 is unprecedented for the 1905 through 2009 period. Additionally, coincident with the increase in deficit near 2000, mean NH runoff also increased due to increases in P. We explain the apparent contradiction of concurrent increases in deficit and increases in runoff.

  9. Aging increases oxidative stress and renal expression of oxidant and antioxidant enzymes that are associated with an increased trend in systolic blood pressure.

    Science.gov (United States)

    Gomes, Pedro; Simão, Sónia; Silva, Elisabete; Pinto, Vanda; Amaral, João S; Afonso, Joana; Serrão, Maria Paula; Pinho, Maria João; Soares-da-Silva, Patrício

    2009-01-01

    The aim of this study was to investigate whether the effects of aging on oxidative stress markers and expression of major oxidant and antioxidant enzymes associate with impairment of renal function and increases in blood pressure. To explore this, we determined age-associated changes in lipid peroxidation (urinary malondialdehyde), plasma and urinary hydrogen peroxide (H(2)O(2)) levels, as well as renal H(2)O(2) production, and the expression of oxidant and antioxidant enzymes in young (13 weeks) and old (52 weeks) male Wistar Kyoto (WKY) rats. Urinary lipid peroxidation levels and H(2)O(2) production by the renal cortex and medulla of old rats were higher than their young counterparts. This was accompanied by overexpression of NADPH oxidase components Nox4 and p22(phox) in the renal cortex of old rats. Similarly, expression of superoxide dismutase (SOD) isoforms 2 and 3 and catalase were increased in the renal cortex from old rats. Renal function parameters (creatinine clearance and fractional excretion of sodium), diastolic blood pressure and heart rate were not affected by aging, although slight increases in systolic blood pressure were observed during this 52-week period. It is concluded that overexpression of renal Nox4 and p22(phox) and the increases in renal H(2)O(2) levels in aged WKY does not associate with renal functional impairment or marked increases in blood pressure. It is hypothesized that lack of oxidative stress-associated effects in aged WKY rats may result from increases in antioxidant defenses that counteract the damaging effects of H(2)O(2).

  10. Interaction of Vaccination and Reduction of Antibiotic Use Drives Unexpected Increase of Pneumococcal Meningitis.

    Science.gov (United States)

    de Cellès, Matthieu Domenech; Pons-Salort, Margarita; Varon, Emmanuelle; Vibet, Marie-Anne; Ligier, Caroline; Letort, Véronique; Opatowski, Lulla; Guillemot, Didier

    2015-06-11

    Antibiotic-use policies may affect pneumococcal conjugate-vaccine effectiveness. The reported increase of pneumococcal meningitis from 2001 to 2009 in France, where a national campaign to reduce antibiotic use was implemented in parallel to the introduction of the 7-valent conjugate vaccine, provides unique data to assess these effects. We constructed a mechanistic pneumococcal transmission model and used likelihood to assess the ability of competing hypotheses to explain that increase. We find that a model integrating a fitness cost of penicillin resistance successfully explains the overall and age-stratified pattern of serotype replacement. By simulating counterfactual scenarios of public health interventions in France, we propose that this fitness cost caused a gradual and pernicious interaction between the two interventions by increasing the spread of nonvaccine, penicillin-susceptible strains. More generally, our results indicate that reductions of antibiotic use may counteract the benefits of conjugate vaccines introduced into countries with low vaccine-serotype coverages and high-resistance frequencies. Our findings highlight the key role of antibiotic use in vaccine-induced serotype replacement and suggest the need for more integrated approaches to control pneumococcal infections.

  11. An Educational Intervention Designed to Increase Women's Leadership Self-Efficacy

    Science.gov (United States)

    Isaac, Carol; Kaatz, Anna; Lee, Barbara; Carnes, Molly

    2012-01-01

    Women are sparsely represented in leadership in academic science, technology, engineering, mathematics, and medicine (STEMM). Cultural stereotypes about men, women, and leaders influence the attitudes, judgments, and decisions that others make about women and the choices women make for themselves. Multilevel interventions are needed to counteract the impact of these pervasive and easily activated stereotypes, which conspire in multiple ways to constrain women's entry, persistence, and advancement in academic STEMM. We describe an individual-level educational intervention. Using the transtheoretical model of behavioral change as a framework, we assessed the success of a semester course on increasing women's leadership self-efficacy for the first three cohorts of course participants (n = 30). Pre/post questionnaires showed gains in leadership self-efficacy, personal mastery, and self-esteem, and decreases in perceived constraints. Qualitative text analysis of weekly journals indicated increasing leadership self-efficacy as course participants applied course information and integrated strategies to mitigate the impact of societal stereotypes into their own leadership practices. Follow-up queries of the first two cohorts supported the enduring value of course participation. We conclude that providing strategies to recognize and mitigate the impact of gender stereotypes is effective in increasing leadership self-efficacy in women at early stages of academic STEMM careers. PMID:22949427

  12. An educational intervention designed to increase women's leadership self-efficacy.

    Science.gov (United States)

    Isaac, Carol; Kaatz, Anna; Lee, Barbara; Carnes, Molly

    2012-01-01

    Women are sparsely represented in leadership in academic science, technology, engineering, mathematics, and medicine (STEMM). Cultural stereotypes about men, women, and leaders influence the attitudes, judgments, and decisions that others make about women and the choices women make for themselves. Multilevel interventions are needed to counteract the impact of these pervasive and easily activated stereotypes, which conspire in multiple ways to constrain women's entry, persistence, and advancement in academic STEMM. We describe an individual-level educational intervention. Using the transtheoretical model of behavioral change as a framework, we assessed the success of a semester course on increasing women's leadership self-efficacy for the first three cohorts of course participants (n = 30). Pre/post questionnaires showed gains in leadership self-efficacy, personal mastery, and self-esteem, and decreases in perceived constraints. Qualitative text analysis of weekly journals indicated increasing leadership self-efficacy as course participants applied course information and integrated strategies to mitigate the impact of societal stereotypes into their own leadership practices. Follow-up queries of the first two cohorts supported the enduring value of course participation. We conclude that providing strategies to recognize and mitigate the impact of gender stereotypes is effective in increasing leadership self-efficacy in women at early stages of academic STEMM careers.

  13. Increasing instruction time in school does increase learning

    DEFF Research Database (Denmark)

    Andersen, Simon Calmar; Humlum, Maria; Nandrup, Anne Brink

    2016-01-01

    Increasing instruction time in school is a central element in the attempts of many governments to improve student learning, but prior research—mainly based on observational data—disputes the effect of this approach and points out the potential negative effects on student behavior. Based on a large......-scale, cluster-randomized trial, we find that increasing instruction time increases student learning and that a general increase in instruction time is at least as efficient as an expert-developed, detailed teaching program that increases instruction with the same amount of time. These findings support the value...... of increased instruction time....

  14. Effects of shrub and tree cover increase on the near-surface atmosphere in northern Fennoscandia

    Directory of Open Access Journals (Sweden)

    J. H. Rydsaa

    2017-09-01

    Full Text Available Increased shrub and tree cover in high latitudes is a widely observed response to climate change that can lead to positive feedbacks to the regional climate. In this study we evaluate the sensitivity of the near-surface atmosphere to a potential increase in shrub and tree cover in the northern Fennoscandia region. We have applied the Weather Research and Forecasting (WRF model with the Noah-UA land surface module in evaluating biophysical effects of increased shrub cover on the near-surface atmosphere at a fine resolution (5.4 km  ×  5.4 km. Perturbation experiments are performed in which we prescribe a gradual increase in taller vegetation in the alpine shrub and tree cover according to empirically established bioclimatic zones within the study region. We focus on the spring and summer atmospheric response. To evaluate the sensitivity of the atmospheric response to inter-annual variability in climate, simulations were conducted for two contrasting years, one warm and one cold. We find that shrub and tree cover increase leads to a general increase in near-surface temperatures, with the highest influence seen during the snowmelt season and a more moderate effect during summer. We find that the warming effect is stronger in taller vegetation types, with more complex canopies leading to decreases in the surface albedo. Counteracting effects include increased evapotranspiration, which can lead to increased cloud cover, precipitation, and snow cover. We find that the strength of the atmospheric feedback is sensitive to snow cover variations and to a lesser extent to summer temperatures. Our results show that the positive feedback to high-latitude warming induced by increased shrub and tree cover is a robust feature across inter-annual differences in meteorological conditions and will likely play an important role in land–atmosphere feedback processes in the future.

  15. Can a fifty percent increase in public sector wages improve the position of public sector employees in the long run? An assessment of the public-private income gap in Hungary

    OpenAIRE

    Szilvia Hamori; Anna Lovasz

    2011-01-01

    We provide a detailed descriptive analysis of the long-term effects of the 50 percent public sector wage increase initiated by the government in 2002 in order to improve the relative situation of public sector workers. The aim of this policy was to attract high quality workers to the public sector, and to counteract the problem of "brain drain," the loss of high-skilled workers to abroad. To study the effects on the public-private income gap - and on high-skilled workers in particular - we em...

  16. Dominant effect of increasing forest biomass on evapotranspiration: interpretations of movement in Budyko space

    Science.gov (United States)

    Jaramillo, Fernando; Cory, Neil; Arheimer, Berit; Laudon, Hjalmar; van der Velde, Ype; Hasper, Thomas B.; Teutschbein, Claudia; Uddling, Johan

    2018-01-01

    During the last 6 decades, forest biomass has increased in Sweden mainly due to forest management, with a possible increasing effect on evapotranspiration. However, increasing global CO2 concentrations may also trigger physiological water-saving responses in broadleaf tree species, and to a lesser degree in some needleleaf conifer species, inducing an opposite effect. Additionally, changes in other forest attributes may also affect evapotranspiration. In this study, we aimed to detect the dominating effect(s) of forest change on evapotranspiration by studying changes in the ratio of actual evapotranspiration to precipitation, known as the evaporative ratio, during the period 1961-2012. We first used the Budyko framework of water and energy availability at the basin scale to study the hydroclimatic movements in Budyko space of 65 temperate and boreal basins during this period. We found that movements in Budyko space could not be explained by climatic changes in precipitation and potential evapotranspiration in 60 % of these basins, suggesting the existence of other dominant drivers of hydroclimatic change. In both the temperate and boreal basin groups studied, a negative climatic effect on the evaporative ratio was counteracted by a positive residual effect. The positive residual effect occurred along with increasing standing forest biomass in the temperate and boreal basin groups, increasing forest cover in the temperate basin group and no apparent changes in forest species composition in any group. From the three forest attributes, standing forest biomass was the one that could explain most of the variance of the residual effect in both basin groups. These results further suggest that the water-saving response to increasing CO2 in these forests is either negligible or overridden by the opposite effect of the increasing forest biomass. Thus, we conclude that increasing standing forest biomass is the dominant driver of long-term and large-scale evapotranspiration

  17. Dominant effect of increasing forest biomass on evapotranspiration: interpretations of movement in Budyko space

    Directory of Open Access Journals (Sweden)

    F. Jaramillo

    2018-01-01

    Full Text Available During the last 6 decades, forest biomass has increased in Sweden mainly due to forest management, with a possible increasing effect on evapotranspiration. However, increasing global CO2 concentrations may also trigger physiological water-saving responses in broadleaf tree species, and to a lesser degree in some needleleaf conifer species, inducing an opposite effect. Additionally, changes in other forest attributes may also affect evapotranspiration. In this study, we aimed to detect the dominating effect(s of forest change on evapotranspiration by studying changes in the ratio of actual evapotranspiration to precipitation, known as the evaporative ratio, during the period 1961–2012. We first used the Budyko framework of water and energy availability at the basin scale to study the hydroclimatic movements in Budyko space of 65 temperate and boreal basins during this period. We found that movements in Budyko space could not be explained by climatic changes in precipitation and potential evapotranspiration in 60 % of these basins, suggesting the existence of other dominant drivers of hydroclimatic change. In both the temperate and boreal basin groups studied, a negative climatic effect on the evaporative ratio was counteracted by a positive residual effect. The positive residual effect occurred along with increasing standing forest biomass in the temperate and boreal basin groups, increasing forest cover in the temperate basin group and no apparent changes in forest species composition in any group. From the three forest attributes, standing forest biomass was the one that could explain most of the variance of the residual effect in both basin groups. These results further suggest that the water-saving response to increasing CO2 in these forests is either negligible or overridden by the opposite effect of the increasing forest biomass. Thus, we conclude that increasing standing forest biomass is the dominant driver of long-term and large

  18. Strong increase of solar panels

    International Nuclear Information System (INIS)

    Segers, R.; Janssen, S.

    2012-01-01

    The number of installed solar panels in 2011 has increased again. 40 megawatt of new panels have been installed. This increase is twice as high as the year before. The production of solar power increased to 90 million kWh in 2011 as a result of this expansion. However, the share of solar power in total energy use is still very limited. [nl

  19. Responses to ozone pollution of alfalfa exposed to increasing salinity levels

    Energy Technology Data Exchange (ETDEWEB)

    Maggio, Albino; Chiaranda, Fabrizio Quaglietta; Cefariello, Roberto [DIAAT, Naples University Federico II, via Universita 100, 80055 Portici (Italy); Fagnano, Massimo, E-mail: fagnano@unina.i [DIAAT, Naples University Federico II, via Universita 100, 80055 Portici (Italy)

    2009-05-15

    Stomatal closure and biosynthesis of antioxidant molecules are two fundamental components of the physiological machinery that lead to stress adaptation during plant's exposure to salinity. Since high stomatal resistance may also contribute in counteracting O{sub 3} damages, we hypothesized that soil salinization may increase O{sub 3} tolerance of crops. An experiment was performed with alfalfa grown in filtered (AOT40 = 0 in both years) and non-filtered (AOT40 = 9.7 in 2005 and 6.9 ppm h in 2006) open-top chambers. Alfalfa yield was reduced by O{sub 3} (-33%) only in plants irrigated with salt-free water, while the increasing levels of soil salinity until 1.06 dS m{sup -1} reduced both stomatal conductance and plant O{sub 3} uptake, thus linearly reducing O{sub 3} effects on yield. Therefore a reliable flux-based model for assessing the effects of O{sub 3} on crop yield should take into account soil salinity. - Moderate saline stress can reduce ozone uptake and yield losses in alfalfa plants.

  20. Responses to ozone pollution of alfalfa exposed to increasing salinity levels

    International Nuclear Information System (INIS)

    Maggio, Albino; Chiaranda, Fabrizio Quaglietta; Cefariello, Roberto; Fagnano, Massimo

    2009-01-01

    Stomatal closure and biosynthesis of antioxidant molecules are two fundamental components of the physiological machinery that lead to stress adaptation during plant's exposure to salinity. Since high stomatal resistance may also contribute in counteracting O 3 damages, we hypothesized that soil salinization may increase O 3 tolerance of crops. An experiment was performed with alfalfa grown in filtered (AOT40 = 0 in both years) and non-filtered (AOT40 = 9.7 in 2005 and 6.9 ppm h in 2006) open-top chambers. Alfalfa yield was reduced by O 3 (-33%) only in plants irrigated with salt-free water, while the increasing levels of soil salinity until 1.06 dS m -1 reduced both stomatal conductance and plant O 3 uptake, thus linearly reducing O 3 effects on yield. Therefore a reliable flux-based model for assessing the effects of O 3 on crop yield should take into account soil salinity. - Moderate saline stress can reduce ozone uptake and yield losses in alfalfa plants.

  1. Bee pollination increases yield quantity and quality of cash crops in Burkina Faso, West Africa.

    Science.gov (United States)

    Stein, Katharina; Coulibaly, Drissa; Stenchly, Kathrin; Goetze, Dethardt; Porembski, Stefan; Lindner, André; Konaté, Souleymane; Linsenmair, Eduard K

    2017-12-18

    Mutualistic biotic interactions as among flowering plants and their animal pollinators are a key component of biodiversity. Pollination, especially by insects, is a key element in ecosystem functioning, and hence constitutes an ecosystem service of global importance. Not only sexual reproduction of plants is ensured, but also yields are stabilized and genetic variability of crops is maintained, counteracting inbreeding depression and facilitating system resilience. While experiencing rapid environmental change, there is an increased demand for food and income security, especially in sub-Saharan communities, which are highly dependent on small scale agriculture. By combining exclusion experiments, pollinator surveys and field manipulations, this study for the first time quantifies the contribution of bee pollinators to smallholders' production of the major cash crops, cotton and sesame, in Burkina Faso. Pollination by honeybees and wild bees significantly increased yield quantity and quality on average up to 62%, while exclusion of pollinators caused an average yield gap of 37% in cotton and 59% in sesame. Self-pollination revealed inbreeding depression effects on fruit set and low germination rates in the F1-generation. Our results highlight potential negative consequences of any pollinator decline, provoking risks to agriculture and compromising crop yields in sub-Saharan West Africa.

  2. Increasing tobacco taxes : A cheap tool to increase public health

    NARCIS (Netherlands)

    van Baal, Pieter H. M.; Brouwer, Werner B. F.; Hoogenveen, Rudolf T.; Feenstra, Talitha L.

    Introduction: Several studies have estimated health effects resulting from tobacco tax increases. However, studies on the cost effectiveness of tobacco taxes are scarce. The aim of this study was to estimate the cost effectiveness of tobacco tax increases from a health care perspective, explicitly

  3. Increasing diversity in radiologic technology.

    Science.gov (United States)

    Carwile, Laura

    2003-01-01

    Diversity is increasingly important in the radiologic technology workplace. For significant changes to occur in work force diversity, educators must first recruit and retain students from a wide variety of backgrounds. This article examines personality, race and gender as factors affecting career choice and how educators can use these factors to increase diversity in their programs. An overview of the ASRT's efforts to improve diversity within the profession is presented, along with suggestions for developing effective recruitment and retention plans to increase diversity.

  4. Increasing Access to Special Collections

    Directory of Open Access Journals (Sweden)

    Ricky Erway

    2012-01-01

    Full Text Available In an environment where we increasingly have access to a collective collection of digitized books, special collections will become increasingly invisible if they are not accessible online. In an era of increasing expectations and decreasing budgets, finding ways to streamline some of our processes is the best way to enable us to do more with less. This report details a number of investigations into how access to special collections can be increased. It includes guidance running the gamut from digitization and rights management to policies and procedures.

  5. Assessing and Increasing Physical Activity

    Science.gov (United States)

    Van Camp, Carole M.; Hayes, Lynda B.

    2012-01-01

    Increasing physical activity is a crucial component of any comprehensive approach to combat the growing obesity epidemic. This review summarizes recent behavioral research on the measurement of physical activity and interventions aimed at increasing physical activity and provides directions for future research.

  6. Employee benefits or wage increase?

    Directory of Open Access Journals (Sweden)

    Jiří Duda

    2011-01-01

    Full Text Available The paper comes from a survey done during the years 2007–2009. It focused on employee satisfaction with the provision of employee benefits. The research included 21 companies, 7 companies were from the engineering sector, 7 companies from the food industry, 3 companies represented the budgetary sphere, 3 companies the services sector and one company operates in pharmaceutical industry.The questionnaire survey consisted of 14 questions, including 5 identification-questions. The paper presents results of the questions on dealing with employees’ awareness of employee benefits and on choosing between employees’ preferences of wage increase or increase in value of benefits provided.Employees are informed about all options of providing employee benefits. Only in 3 cases employees stated dissatisfaction with information. This answer was related with the responses to the second monitored question. Employees of these companies preferred pay increases before benefits’ increases. There was no effect of gender of the respondents, neither the influence of the sector of operation, in the preference of increases in wages or in benefits. Exceptions were the employees of companies operating in the financial sector, who preferred employee benefits before a wage increase. It was found that employees of companies who participated in research in 2009, preferred wage increases before the extension of employee benefits, although the value of the net wage increase is lower than the monetary value of benefits increase.The paper is a part of solution of the research plan MSM 6215648904 The Czech economy in the process of integration and globalization, and the development of agricultural sector and the sector of services under the new conditions of the integrated European market.

  7. The bile sequestrant cholestyramine increases survival in a rabbit model of brodifacoum poisoning.

    Science.gov (United States)

    Lindeblad, Matthew; Lyubimov, Alexander; van Breemen, Richard; Gierszal, Kamil; Weinberg, Guy; Rubinstein, Israel; Feinstein, Douglas L

    2018-06-12

    Patients exposed to long acting anticoagulant rodenticides (LAARs) are typically administered large amounts of oral vitamin K1 (VK1) to counteract life-threatening anti-coagulant effects. While VK1 treatment effectively prevents mortality, additional methods are needed to reduce the long duration of VK1 treatment which can last for months at high expense. We developed a model of brodifacoum (BDF) poisoning, one of the most potent LAARs, in adult male New Zealand White (NZW) rabbits. The LD50 for oral BDF was determined to be 192 μg/kg, similar to that calculated for adult rats. However, in contrast to rats, NZW rabbits exhibited severe internal hemorrhage including in the brain, symptoms which mimic what occurs in cases of human poisoning. Similar to warfarin, BDF and other LAARs undergo enterohepatic recirculation which contributes to their long half-lives. We therefore tested effects of cholestyramine (CSA), an FDA-approved bile sequestrant, on BDF-induced mortality. When given daily (0.67 gm/kg, oral) starting the day of BDF administration, CSA reduced mortality from 67% to 11%. At the same CSA prevented the increase in clotting time, and reduced the decrease in core body temperature due to BDF. Given its excellent safety record and that it is approved for children older than 6 years, these findings suggest CSA could be considered as an adjunct to VK1 for treatment of LAAR poisoning.

  8. Acclimation increases freezing stress response of Arabidopsis thaliana at proteome level

    KAUST Repository

    Fanucchi, Francesca

    2012-06-01

    This study used 2DE to investigate how Arabidopsis thaliana modulates protein levels in response to freezing stress after sub-lethal exposure at - 10 °C, both in cold-acclimated and in non-acclimated plants. A map was implemented in which 62 spots, corresponding to 44 proteins, were identified. Twenty-two spots were modulated upon treatments, and the corresponding proteins proved to be related to photosynthesis, energy metabolism, and stress response. Proteins demonstrated differences between control and acclimation conditions. Most of the acclimation-responsive proteins were either not further modulated or they were down-modulated by freezing treatment, indicating that the levels reached during acclimation were sufficient to deal with freezing. Anabolic metabolism appeared to be down-regulated in favor of catabolic metabolism. Acclimated plants and plants submitted to freezing after acclimation showed greater reciprocal similarity in protein profiles than either showed when compared both to control plants and to plants frozen without acclimation. The response of non-acclimated plants was aimed at re-modulating photosynthetic apparatus activity, and at increasing the levels of proteins with antioxidant-, molecular chaperone-, or post-transcriptional regulative functions. These changes, even less effective than the acclimation strategy, might allow the injured plastids to minimize the production of non-useful metabolites and might counteract photosynthetic apparatus injuries. © 2012 Elsevier B.V. All rights reserved.

  9. Acclimation increases freezing stress response of Arabidopsis thaliana at proteome level

    KAUST Repository

    Fanucchi, Francesca; Alpi, Emanuele; Olivieri, Stefano; Cannistraci, Carlo; Bachi, Angela; Alpi, Amedeo; Alessio, Massimo

    2012-01-01

    This study used 2DE to investigate how Arabidopsis thaliana modulates protein levels in response to freezing stress after sub-lethal exposure at - 10 °C, both in cold-acclimated and in non-acclimated plants. A map was implemented in which 62 spots, corresponding to 44 proteins, were identified. Twenty-two spots were modulated upon treatments, and the corresponding proteins proved to be related to photosynthesis, energy metabolism, and stress response. Proteins demonstrated differences between control and acclimation conditions. Most of the acclimation-responsive proteins were either not further modulated or they were down-modulated by freezing treatment, indicating that the levels reached during acclimation were sufficient to deal with freezing. Anabolic metabolism appeared to be down-regulated in favor of catabolic metabolism. Acclimated plants and plants submitted to freezing after acclimation showed greater reciprocal similarity in protein profiles than either showed when compared both to control plants and to plants frozen without acclimation. The response of non-acclimated plants was aimed at re-modulating photosynthetic apparatus activity, and at increasing the levels of proteins with antioxidant-, molecular chaperone-, or post-transcriptional regulative functions. These changes, even less effective than the acclimation strategy, might allow the injured plastids to minimize the production of non-useful metabolites and might counteract photosynthetic apparatus injuries. © 2012 Elsevier B.V. All rights reserved.

  10. Chronic pyruvate supplementation increases exploratory activity and brain energy reserves in young and middle-aged mice

    Directory of Open Access Journals (Sweden)

    Hennariikka eKoivisto

    2016-03-01

    Full Text Available Numerous studies have reported neuroprotective effects of pyruvate when given in systemic injections. Impaired glucose uptake and metabolism are found in Alzheimer's disease (AD and in AD mouse models. We tested whether dietary pyruvate supplementation is able to provide added energy supply to brain and thereby attenuate aging- or AD-related cognitive impairment. Mice received ~ 800 mg/kg/day Na-pyruvate in their chow for 2- 6 months. In middle-aged wild-type mice and in 6.5-month-old APP/PS1 mice, pyruvate facilitated spatial learning and increased exploration of a novel odor. However, in passive avoidance task for fear memory, the treatment group was clearly impaired. Independent of age, long-term pyruvate increased explorative behavior, which likely explains the paradoxical impairment in passive avoidance. We also assessed pyruvate effects on body weight, muscle force and endurance, and found no effects. Metabolic post-mortem assays revealed increased energy compounds in nuclear magnetic resonance spectroscopy as well as increased brain glycogen storages in the pyruvate group. Pyruvate supplementation may counteract aging-related behavioral impairment but its beneficial effect seems related to increased explorative activity rather than direct memory enhancement.

  11. Increasing sales by reducing procrastination

    OpenAIRE

    Gjedrem, William Gilje

    2012-01-01

    Master's thesis in Finance In this paper I analyze whether an intervention program increases productivity and sales, by reducing potential procrastination problems that employees face at work. The intervention was introduced to stores in a large retail chain in Norway, and contained different tools that could lead to lower perceived costs of higher effort. In a difference-in-differences analysis I find that the intervention increases sales after a 14 weeks long implementation period. Fu...

  12. Increased Materialistic Trends Among Youth

    OpenAIRE

    Shama Mazahir, Afsheen Masood, Rubab Musarrat

    2016-01-01

    The goal of this qualitative research is to investigate the increased sense of materialism among youth. The main research question is to identify the factors which are causing materialism among youth. The sample of this research included 25 people, age group 18-25 years obtained from students that are enrolled in universities. The interpretive phenomenological approach was taken which was based on semi-structured interviews. The findings revealed that materialistic trends are increasing among...

  13. Increased Materialistic Trends among Youth

    OpenAIRE

    Afsheen Masood; Rubab Musarrat; Shama Mazahir

    2016-01-01

    The goal of this qualitative research is to investigate the increased sense of materialism among youth. The main research question is to identify the factors which are causing materialism among youth. The sample of this research included 25 people, age group 18-25 years obtained from students that are enrolled in universities. The interpretive phenomenological approach was taken which was based on semi-structured interviews. The findings revealed that materialistic trends are increasing among...

  14. Increasing incidence of pyogenic spondylodiscitis

    DEFF Research Database (Denmark)

    Kehrer, Michala; Pedersen, Court; Jensen, Thøger G

    2014-01-01

    Smaller studies indicate that the incidence of pyogenic spondylodiscitis is increasing, possible related to a growing elderly population. Data supporting this is sparse, and we therefore studied patient characteristics and changes in spondylodiscitis incidence 1995-2008.......Smaller studies indicate that the incidence of pyogenic spondylodiscitis is increasing, possible related to a growing elderly population. Data supporting this is sparse, and we therefore studied patient characteristics and changes in spondylodiscitis incidence 1995-2008....

  15. Requests for body computed tomography: increasing workload, increasing indications and increasing age

    International Nuclear Information System (INIS)

    Toms, A.P.; Cash, C.J.C.; Dixon, A.K.; Linton, S.J.

    2001-01-01

    Increasing numbers of increasingly elderly patients were being examined in our Body CT department. At the same time, some of our clinical colleagues perceived that their patients might be discriminated against on the basis of their age when allocating CT time. We therefore studied the population trends in our department over a 10-year period. The ages of patients attending the Body CT department were collected from the hospital's computer information system from 1995 to 2000 and from handwritten logbooks for the months of September 1988 and 1998. Comparison was made with population trends within the hospital and local demographic data. There has been an average increase of 11% per annum in the number of examinations performed in the Body CT unit. The average age of patients examined increased from 52.7 years in 1988 to 58.9 years in 1998. The largest increase occurred in the over 75-year population (18% rise per annum). Hospital and local demographic population profiles changed little during the same period. We are performing increasing numbers of body CT examinations on increasingly elderly patients. This is probably due to an increased willingness to investigate and treat elderly patients, rather than changes in the local population. There is no evidence of a general discriminatory policy on the basis of age. (orig.)

  16. Pulsed electric field increases reproduction.

    Science.gov (United States)

    Panagopoulos, Dimitris J

    2016-01-01

    Purpose To study the effect of pulsed electric field - applied in corona discharge photography - on Drosophila melanogaster reproduction, possible induction of DNA fragmentation, and morphological alterations in the gonads. Materials and methods Animals were exposed to different field intensities (100, 200, 300, and 400 kV/m) during the first 2-5 days of their adult lives, and the effect on reproductive capacity was assessed. DNA fragmentation during early- and mid-oogenesis was investigated by application of the TUNEL (Terminal deoxynucleotide transferase dUTP Nick End Labeling) assay. Sections of follicles after fixation and embedding in resins were observed for possible morphological/developmental abnormalities. Results The field increased reproduction by up to 30% by increasing reproductive capacity in both sexes. The effect increased with increasing field intensities. The rate of increase diminished at the strongest intensities. Slight induction of DNA fragmentation was observed exclusively in the nurse (predominantly) and follicle cells, and exclusively at the two most sensitive developmental stages, i.e., germarium and predominantly stage 7-8. Sections of follicles from exposed females at stages of early and mid-oogennesis other than germarium and stages 7-8 did not reveal abnormalities. Conclusions (1) The specific type of electric field may represent a mild stress factor, inducing DNA fragmentation and cell death in a small percentage of gametes, triggering the reaction of the animal's reproductive system to increase the rate of gametogenesis in order to compensate the loss of a small number of gametes. (2) The nurse cells are the most sensitive from all three types of egg chamber cells. (3) The mid-oogenesis checkpoint (stage 7-8) is more sensitive to this field than the early oogenesis one (germarium) in contrast to microwave exposure. (4) Possible therapeutic applications, or applications in increasing fertility, should be investigated.

  17. Food allergy: is prevalence increasing?

    Science.gov (United States)

    Tang, Mimi L K; Mullins, Raymond J

    2017-03-01

    It is generally accepted that the prevalence of food allergy has been increasing in recent decades, particularly in westernised countries, yet high-quality evidence that is based on challenge confirmed diagnosis of food allergy to support this assumption is lacking because of the high cost and potential risks associated with conducting food challenges in large populations. Accepting this caveat, the use of surrogate markers for diagnosis of food allergy (such as nationwide data on hospital admissions for food anaphylaxis or clinical history in combination with allergen-specific IgE (sIgE) measurement in population-based cohorts) has provided consistent evidence for increasing prevalence of food allergy at least in western countries, such as the UK, United States and Australia. Recent reports that children of East Asian or African ethnicity who are raised in a western environment (Australia and United States respectively) have an increased risk of developing food allergy compared with resident Caucasian children suggest that food allergy might also increase across Asian and African countries as their economies grow and populations adopt a more westernised lifestyle. Given that many cases of food allergy persist, mathematical principles would predict a continued increase in food allergy prevalence in the short to medium term until such time as an effective treatment is identified to allow the rate of disease resolution to be equal to or greater than the rate of new cases. © 2017 Royal Australasian College of Physicians.

  18. Increased chromosome radiosensitivity during pregnancy

    International Nuclear Information System (INIS)

    Ricoul, Michelle; Sabatier, Laure; Dutrillaux, Bernard

    1997-01-01

    It was necessary to consider the risks of exposure of pregnant women, not only in relation to the child, but also in relation to their own hypersensitivity. We have demonstrated that pregnancy increases radiosensitivity of chromosome in the mouse at the end of gestation. This is of importance since it may have implications on radioprotection of pregnant women and give experimental guidelines to the problems of hypersensitivity to drugs and cancer aggravation during pregnancy. Blood obtained from women at various times of pregnancy was exposed to ionizing radiations. By comparison to non-pregnant women, an increase in chromosome breakage was observed in metaphases from lymphocytes, after short-term culture in the presence of the serum of the same donor. Immediately after delivery, this increase in radiosensitivity disappeared. In a prospective study, serial analyses showed a very strong correlation between the amount of pregnancy hormones, progesterone in particular, and the increase in radiosensitivity. Pregnant women may have an increased sensitivity to ionizing radiation during the second half of their pregnancy. This study provides the first evidence in human that radiosensitivity may vary in relation to physiological conditions

  19. Increasing work-time influence

    DEFF Research Database (Denmark)

    Nabe-Nielsen, Kirsten; Garde, Anne Helene; Aust, Birgit

    2012-01-01

    This quasi-experimental study investigated how an intervention aiming at increasing eldercare workers' influence on their working hours affected the flexibility, variability, regularity and predictability of the working hours. We used baseline (n = 296) and follow-up (n = 274) questionnaire data......), or discussion of working hours (subgroup C). Only computerised self-scheduling changed the working hours and the way they were planned. These changes implied more flexible but less regular working hours and an experience of less predictability and less continuity in the care of clients and in the co...... that while increasing the individual flexibility, increasing work-time influence may also result in decreased regularity of the working hours and less continuity in the care of clients and co-operation with colleagues....

  20. Increased Materialistic Trends among Youth

    Directory of Open Access Journals (Sweden)

    Afsheen Masood

    2016-12-01

    Full Text Available The goal of this qualitative research is to investigate the increased sense of materialism among youth. The main research question is to identify the factors which are causing materialism among youth. The sample of this research included 25 people, age group 18-25 years obtained from students that are enrolled in universities. The interpretive phenomenological approach was taken which was based on semi-structured interviews. The findings revealed that materialistic trends are increasing among youth nowadays. Because thought patterns of youth and societal demands have changed totally. Factors that are increasing materialism include social media, brand consciousness; self-centeredness; fake personality development and desire to be socially accepted. The implications indicate that materialistic trend should stop by controlling the social media possession among youth which is the primary source of enhancing materialism among youth.

  1. Diffuse radiation increases global ecosystem-level water-use efficiency

    Science.gov (United States)

    Moffat, A. M.; Reichstein, M.; Cescatti, A.; Knohl, A.; Zaehle, S.

    2012-12-01

    Current environmental changes lead not only to rising atmospheric CO2 levels and air temperature but also to changes in air pollution and thus the light quality of the solar radiation reaching the land-surface. While rising CO2 levels are thought to enhance photosynthesis and closure of stomata, thus leading to relative water savings, the effect of diffuse radiation on transpiration by plants is less clear. It has been speculated that the stimulation of photosynthesis by increased levels of diffuse light may be counteracted by higher transpiration and consequently water depletion and drought stress. Ultimately, in water co-limited systems, the overall effect of diffuse radiation will depend on the sensitivity of canopy transpiration versus photosynthesis to diffuse light, i.e. whether water-use efficiency changes with relative levels of diffuse light. Our study shows that water-use efficiency increases significantly with higher fractions of diffuse light. It uses the ecosystem-atmosphere gas-exchange observations obtained with the eddy covariance method at 29 flux tower sites. In contrast to previous global studies, the analysis is based directly on measurements of diffuse radiation. Its effect on water-use efficiency was derived by analyzing the multivariate response of carbon and water fluxes to radiation and air humidity using a purely empirical approach based on artificial neural networks. We infer that per unit change of diffuse fraction the water-use efficiency increases up to 40% depending on diffuse fraction levels and ecosystem type. Hence, in regions with increasing diffuse radiation positive effects on primary production are expected even under conditions where water is co-limiting productivity.

  2. Increased burnup of fuel elements

    International Nuclear Information System (INIS)

    Ahlf, J.

    1983-01-01

    The specialists' group for fuel elements of the Kerntechnische Gesellschaft e.V. held a meeting on ''Increased Burnup of Fuel Elements'' on 9th and 10th of November 1982 at the GKSS Research Center Geesthacht. Most papers dealt with the problems of burnup increase of fuel elements for light water reactors with respect to fuel manufacturing, power plant operation and reprocessing. Review papers were given on the burnup limits for high temperature gas cooled reactors and sodium fast breeder reactors. The meeting ended with a presentation of the technical equipment of the hot laboratory of the GKSS and the programs which are in progress there. (orig.) [de

  3. Transvenous stimulation of the renal sympathetic nerves increases systemic blood pressure: a potential new treatment option for neurocardiogenic syncope.

    Science.gov (United States)

    Madhavan, Malini; Desimone, Christopher V; Ebrille, Elisa; Mulpuru, Siva K; Mikell, Susan B; Johnson, Susan B; Suddendorf, Scott H; Ladewig, Dorothy J; Gilles, Emily J; Danielsen, Andrew J; Asirvatham, Samuel J

    2014-10-01

    Neurocardiogenic syncope (NCS) is a common and sometimes debilitating disorder, with no consistently effective treatment. NCS is due to a combination of bradycardia and vasodilation leading to syncope. Although pacemaker devices have been tried in treating the bradycardic aspect of NCS, no device-based therapy exists to treat the coexistent vasodilation that occurs. The renal sympathetic innervation has been the target of denervation to treat hypertension. We hypothesized that stimulation of the renal sympathetic nerves can increase blood pressure and counteract vasodilation in NCS. High-frequency stimulation (800-900 pps, 10 V, 30-200 seconds) was performed using a quadripolar catheter in the renal vein of 7 dogs and 1 baboon. A significant increase in blood pressure (BP; mean [SD] systolic BP 117 [±28] vs. 128 [±33], diastolic BP 75 [±19] vs. 87 [±29] mmHg) was noted during the stimulation, which returned to baseline after cessation of stimulation. The mean increase in systolic and diastolic BP was 13.0 (±3.3) (P = 0.006) and 10.2 (±4.6) (P = 0.08), respectively. We report the first ever study of feasibility and safety of high-frequency electrical stimulation of the renal sympathetic innervation to increase BP in animal models. This has potential applications in the treatment of hypotensive states such as NCS. © 2014 Wiley Periodicals, Inc.

  4. Perioperative Testosterone Supplementation Increases Lean Mass in Healthy Men Undergoing Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Trial.

    Science.gov (United States)

    Wu, Brian; Lorezanza, Dan; Badash, Ido; Berger, Max; Lane, Christianne; Sum, Jonathan C; Hatch, George F; Schroeder, E Todd

    2017-08-01

    Rehabilitation after repair of the anterior cruciate ligament (ACL) is complicated by the loss of leg muscle mass and strength. Prior studies have shown that preoperative rehabilitation may improve muscle strength and postoperative outcomes. Testosterone supplementation may likewise counteract this muscle loss and potentially improve clinical outcomes. The purpose was to investigate the effect of perioperative testosterone administration on lean mass after ACL reconstruction in men and to examine the effects of testosterone on leg strength and clinical outcome scores. It was hypothesized that testosterone would increase lean mass and leg strength and improve clinical outcome scores relative to placebo. Randomized controlled trial; Level of evidence, 1. Male patients (N = 13) scheduled for ACL reconstruction were randomized into 2 groups: testosterone and placebo. Participants in the testosterone group received 200 mg of intramuscular testosterone weekly for 8 weeks beginning 2 weeks before surgery. Participants in the placebo group received saline following the same schedule. Both groups participated in a standard rehabilitation protocol. The primary outcome was the change in total lean body mass at 6 and 12 weeks. Secondary outcomes were extensor muscle strength, Tegner activity score, and Knee injury and Osteoarthritis Outcome Score. There was an increase in lean mass of a mean 2.7 ± 1.7 kg at 6 weeks postoperatively in the testosterone group compared with a decrease of a mean 0.1 ± 1.5 kg in the placebo group ( P = .01). Extensor muscle strength of the uninjured leg also increased more from baseline in the testosterone group (+20.8 ± 25.6 Nm) compared with the placebo group (-21.4 ± 36.7 Nm) at 12 weeks ( P = .04). There were no significant between-group differences in injured leg strength or clinical outcome scores. There were no negative side effects of testosterone noted. Perioperative testosterone supplementation increased lean mass 6 weeks after ACL

  5. Big increase in US ethanol

    Energy Technology Data Exchange (ETDEWEB)

    1981-07-10

    US ethanol capacity is expected to reach 600 million US gal/year by the end of 1982, according to a report from the AIChE. Although this is a six-fold increase over capacity installed in 1979 it is still less than 1% of US domestic motor fuel supply.

  6. Crop diversity for yield increase.

    Directory of Open Access Journals (Sweden)

    Chengyun Li

    2009-11-01

    Full Text Available Traditional farming practices suggest that cultivation of a mixture of crop species in the same field through temporal and spatial management may be advantageous in boosting yields and preventing disease, but evidence from large-scale field testing is limited. Increasing crop diversity through intercropping addresses the problem of increasing land utilization and crop productivity. In collaboration with farmers and extension personnel, we tested intercropping of tobacco, maize, sugarcane, potato, wheat and broad bean--either by relay cropping or by mixing crop species based on differences in their heights, and practiced these patterns on 15,302 hectares in ten counties in Yunnan Province, China. The results of observation plots within these areas showed that some combinations increased crop yields for the same season between 33.2 and 84.7% and reached a land equivalent ratio (LER of between 1.31 and 1.84. This approach can be easily applied in developing countries, which is crucial in face of dwindling arable land and increasing food demand.

  7. Electromigration early resistance increase measurements

    NARCIS (Netherlands)

    Niehof, J.; Flinn, P.A.; Maloney, T.J.

    1993-01-01

    An early resistance change measurement set-up, using an AC bridge technique, has been developed, and measurements have been performed. Large sample-to-sample variations occur. The characteristic time for the resistance change curve is shorter for resistance increase (under current stress) than for

  8. Effects of increased biofuel utilization

    International Nuclear Information System (INIS)

    Bahr, J.; Blad, B.; Hillring, B.

    1996-01-01

    This report is a compilation of present knowledge regarding the effects of an increased use of biomass fuels. Main areas treated are: Availability of raw materials; Effects on forestry and agriculture; Transportation; Areas of use; Cost and price formation; Emission to the atmosphere, and effect on the climate; and Effect on employment and regional aspects. 29 tabs

  9. INCREASED RELIABILITY OF ELECTRIC BLASTING

    OpenAIRE

    Kashuba, Oleh Ivanovych; Skliarov, L I; Skliarov, A L

    2017-01-01

    The problems of improving reliability of an electric blasting method using electric detonators with nichrome filament bridges. It was revealed that in the calculation of the total resistance of the explosive network it is necessary to increase to 24% of the nominal value

  10. Carbohydrase and protease supplementation increased ...

    African Journals Online (AJOL)

    A trial was conducted to evaluate whether the addition of commercial enzyme preparations containing carbohydrases and a protease would increase the available metabolizable energy (ME) of maize-soya-based broiler diets. Seven thousand five hundred and sixty (7560) day-old Ross 788 chicks were randomly allocated ...

  11. How To Increase Advertising Revenue.

    Science.gov (United States)

    Mitchell, Carmen

    1995-01-01

    Describes advertising sales strategies to help faculty advisers of community college newspapers increase revenues. Argues that sales representatives should know their product well and maintain demographic information on the paper's readership. Includes strategies for organizing advertising staff, searching for potential clients, and taking charge…

  12. Increased p50/p50 NF-κB Activation in Human Papillomavirus Type 6- or Type 11-Induced Laryngeal Papilloma Tissue

    Science.gov (United States)

    Vancurova, Ivana; Wu, Rong; Miskolci, Veronika; Sun, Shishinn

    2002-01-01

    We have observed elevated NF-κB DNA-binding activity in nuclear extracts from human papillomavirus type 6- and 11-infected laryngeal papilloma tissues. The predominant DNA-binding species is the p50/p50 homodimer. The elevated NF-κB activity could be correlated with a reduced level of cytoplasmic IκBβ and could be associated with the overexpression of p21CIP1/WAF1 in papilloma cells. Increased NF-κB activity and cytoplasmic accumulation of p21CIP1/WAF1 might counteract death-promoting effects elicited by overexpressed PTEN and reduced activation of Akt and STAT3 previously noted in these tissues. PMID:11773428

  13. Combined role of type IX collagen and cartilage oligomeric matrix protein in cartilage matrix assembly: Cartilage oligomeric matrix protein counteracts type IX collagen-induced limitation of cartilage collagen fibril growth in mouse chondrocyte cultures

    NARCIS (Netherlands)

    Blumbach, K.; Bastiaansen-Jenniskens, Y.M.; Groot, J. de; Paulsson, M.; Osch, G.J.V.M. van; Zaucke, F.

    2009-01-01

    Objective. Defects in the assembly and composition of cartilage extracellular matrix are likely to result in impaired matrix integrity and increased susceptibility to cartilage degeneration. The aim of this study was to determine the functional interaction of the collagen fibril-associated proteins

  14. Increased NMDA receptor inhibition at an increased Sevoflurane MAC

    Directory of Open Access Journals (Sweden)

    Brosnan Robert J

    2012-06-01

    Full Text Available Abstract Background Sevoflurane potently enhances glycine receptor currents and more modestly decreases NMDA receptor currents, each of which may contribute to immobility. This modest NMDA receptor antagonism by sevoflurane at a minimum alveolar concentration (MAC could be reciprocally related to large potentiation of other inhibitory ion channels. If so, then reduced glycine receptor potency should increase NMDA receptor antagonism by sevoflurane at MAC. Methods Indwelling lumbar subarachnoid catheters were surgically placed in 14 anesthetized rats. Rats were anesthetized with sevoflurane the next day, and a pre-infusion sevoflurane MAC was measured in duplicate using a tail clamp method. Artificial CSF (aCSF containing either 0 or 4 mg/mL strychnine was then infused intrathecally at 4 μL/min, and the post-infusion baseline sevoflurane MAC was measured. Finally, aCSF containing strychnine (either 0 or 4 mg/mL plus 0.4 mg/mL dizocilpine (MK-801 was administered intrathecally at 4 μL/min, and the post-dizocilpine sevoflurane MAC was measured. Results Pre-infusion sevoflurane MAC was 2.26%. Intrathecal aCSF alone did not affect MAC, but intrathecal strychnine significantly increased sevoflurane requirement. Addition of dizocilpine significantly decreased MAC in all rats, but this decrease was two times larger in rats without intrathecal strychnine compared to rats with intrathecal strychnine, a statistically significant (P  Conclusions Glycine receptor antagonism increases NMDA receptor antagonism by sevoflurane at MAC. The magnitude of anesthetic effects on a given ion channel may therefore depend on the magnitude of its effects on other receptors that modulate neuronal excitability.

  15. Economic inequality increases risk taking.

    Science.gov (United States)

    Payne, B Keith; Brown-Iannuzzi, Jazmin L; Hannay, Jason W

    2017-05-02

    Rising income inequality is a global trend. Increased income inequality has been associated with higher rates of crime, greater consumer debt, and poorer health outcomes. The mechanisms linking inequality to poor outcomes among individuals are poorly understood. This research tested a behavioral account linking inequality to individual decision making. In three experiments ( n = 811), we found that higher inequality in the outcomes of an economic game led participants to take greater risks to try to achieve higher outcomes. This effect of unequal distributions on risk taking was driven by upward social comparisons. Next, we estimated economic risk taking in daily life using large-scale data from internet searches. Risk taking was higher in states with greater income inequality, an effect driven by inequality at the upper end of the income distribution. Results suggest that inequality may promote poor outcomes, in part, by increasing risky behavior.

  16. Heavier smoking increases coffee consumption

    DEFF Research Database (Denmark)

    Bjørngaard, Johan H; Nordestgaard, Ask Tybjærg; Taylor, Amy E

    2017-01-01

    Background: There is evidence for a positive relationship between cigarette and coffee consumption in smokers. Cigarette smoke increases metabolism of caffeine, so this may represent a causal effect of smoking on caffeine intake. Methods: We performed Mendelian randomization analyses in the UK...... Biobank ( N  = 114 029), the Norwegian HUNT study ( N  = 56 664) and the Copenhagen General Population Study (CGPS) ( N  = 78 650). We used the rs16969968 genetic variant as a proxy for smoking heaviness in all studies and rs4410790 and rs2472297 as proxies for coffee consumption in UK Biobank and CGPS....... Analyses were conducted using linear regression and meta-analysed across studies. Results: Each additional cigarette per day consumed by current smokers was associated with higher coffee consumption (0.10 cups per day, 95% CI: 0.03, 0.17). There was weak evidence for an increase in tea consumption per...

  17. Depletion of regulatory T cells leads to an exacerbation of delayed-type hypersensitivity arthritis in C57BL/6 mice that can be counteracted by IL-17 blockade

    Science.gov (United States)

    Atkinson, Sara Marie; Hoffmann, Ute; Hamann, Alf; Bach, Emil; Danneskiold-Samsøe, Niels Banhos; Kristiansen, Karsten; Serikawa, Kyle; Fox, Brian; Kruse, Kim; Haase, Claus; Skov, Søren; Nansen, Anneline

    2016-01-01

    ABSTRACT Rodent models of arthritis have been extensively used in the elucidation of rheumatoid arthritis (RA) pathogenesis and are instrumental in the development of therapeutic strategies. Here we utilise delayed-type hypersensitivity arthritis (DTHA), a model in C57BL/6 mice affecting one paw with synchronised onset, 100% penetrance and low variation. We investigate the role of regulatory T cells (Tregs) in DTHA through selective depletion of Tregs and the role of IL-17 in connection with Treg depletion. Given the relevance of Tregs in RA, and the possibility of developing Treg-directed therapies, this approach could be relevant for advancing the understanding of Tregs in inflammatory arthritis. Selective depletion of Tregs was achieved using a Foxp3-DTR-eGFP mouse, which expresses the diphtheria toxin receptor (DTR) and enhanced green fluorescent protein (eGFP) under control of the Foxp3 gene. Anti-IL-17 monoclonal antibody (mAb) was used for IL-17 blockade. Numbers and activation of Tregs increased in the paw and its draining lymph node in DTHA, and depletion of Tregs resulted in exacerbation of disease as shown by increased paw swelling, increased infiltration of inflammatory cells, increased bone remodelling and increased production of inflammatory mediators, as well as increased production of anti-citrullinated protein antibodies. Anti-IL-17 mAb treatment demonstrated that IL-17 is important for disease severity in both the presence and absence of Tregs, and that IL-17 blockade is able to rescue mice from the exacerbated disease caused by Treg depletion and caused a reduction in RANKL, IL-6 and the number of neutrophils. We show that Tregs are important for the containment of inflammation and bone remodelling in DTHA. To our knowledge, this is the first study using the Foxp3-DTR-eGFP mouse on a C57BL/6 background for Treg depletion in an arthritis model, and we here demonstrate the usefulness of the approach to study the role of Tregs and IL-17 in arthritis

  18. Price Increases from Online Privacy

    OpenAIRE

    Ward, Michael R.; Chen, Yu-Ching

    2001-01-01

    Consumers value keeping some information about them private from potential marketers. E-commerce dramatically increases the potential for marketers to accumulate otherwise private information about potential customers. Online marketers claim that this information enables them to better market their products. Policy makers are currently drafting rules to regulate the way in which these marketers can collect, store, and share this information. However, there is little evidence yet either of con...

  19. Increase Productivity Through Knowledge Management

    OpenAIRE

    Gavrikova, Nadezhda Aleksandrovna; Dolgikh, Irina Nikolaevna; Dyrina, E. N.

    2016-01-01

    Increase in competition level requires companies to improve the efficiency of work force use characterized by labor productivity. Professional knowledge of staff and its experience play the key role in it. The results of Extrusion Line operator's working time analysis are performed in this article. The analysis revealed that the reasons of working time ineffective use connected with inadequate information exchange and knowledge management in the company. Authors suggest the way to solve this ...

  20. Mod increases AGR boiler output

    International Nuclear Information System (INIS)

    Jones, W.K.C.; Rider, G.; Taylor, D.E.

    1986-01-01

    During the commissioning runs of the first reactor units at Heysham I and Hartlepool Advanced Gas-cooled Reactors (AGRs), non-uniform temperature distributions were observed across individual boiler units which were more severe than those predicted from the design analysis. This article describes the re-orificing (referruling) of the boilers to overcome this problem. The referruling has reduced boiler sensitivity and resulted in an increase of load of 7 or 8%. (U.K.)

  1. Is surgical workforce diversity increasing?

    Science.gov (United States)

    Andriole, Dorothy A; Jeffe, Donna B; Schechtman, Kenneth B

    2007-03-01

    We sought to determine the extent to which recent increases in levels of gender and racial diversity in the overall resident-physician workforce were evident among core-surgical specialty resident workforces. Chi-square tests for trend assessed the importance of changes from 1996 to 2004 in proportions of women and African Americans in the surgery-resident workforce. Surgery-resident trends were compared with overall resident workforce trends using two-tailed t-tests to compare regression slopes that quantified rates of change over time. Chi-square tests assessed differences between proportions of women and African Americans in the current overall board-certified workforce and their proportions in the surgery board-certified workforce. From 1996 to 2004, proportions of women increased in all seven surgical specialties studied. Compared with the overall trend toward increasing proportions of women in the resident workforce, the trend in one surgical specialty was larger (obstetrics/gynecology, p 0.05), and two were smaller (each p 0.05). Proportions of African Americans decreased in three specialties (each p workforce, except obstetrics/gynecology, remained lower than in the overall board-certified workforce (each p workforces have persisted since 1996 and will likely perpetuate ongoing surgery board-certified workforce disparities.

  2. High Heels Increase Women's Attractiveness.

    Science.gov (United States)

    Guéguen, Nicolas

    2015-11-01

    Research has found that the appearance of women's apparel helps increase their attractiveness as rated by men and that men care more about physical features in potential opposite-sex mates. However, the effect of sartorial appearance has received little interest from scientists. In a series of studies, the length of women's shoe heels was examined. A woman confederate wearing black shoes with 0, 5, or 9 cm heels asked men for help in various circumstances. In Study 1, she asked men to respond to a short survey on gender equality. In Study 2, the confederate asked men and women to participate in a survey on local food habit consumption. In Study 3, men and women in the street were observed while walking in back of the female confederate who dropped a glove apparently unaware of her loss. It was found that men's helping behavior increased as soon as heel length increased. However, heel length had no effect on women's helping behavior. It was also found that men spontaneously approached women more quickly when they wore high-heeled shoes (Study 4). Change in gait, foot-size judgment, and misattribution of sexiness and sexual intent were used as possible explanations.

  3. Does milk increase mucus production?

    Science.gov (United States)

    Bartley, Jim; McGlashan, Susan Read

    2010-04-01

    Excessive milk consumption has a long association with increased respiratory tract mucus production and asthma. Such an association cannot be explained using a conventional allergic paradigm and there is limited medical evidence showing causality. In the human colon, beta-casomorphin-7 (beta-CM-7), an exorphin derived from the breakdown of A1 milk, stimulates mucus production from gut MUC5AC glands. In the presence of inflammation similar mucus overproduction from respiratory tract MUC5AC glands characterises many respiratory tract diseases. beta-CM-7 from the blood stream could stimulate the production and secretion of mucus production from these respiratory glands. Such a hypothesis could be tested in vitro using quantitative RT-PCR to show that the addition of beta-CM-7 into an incubation medium of respiratory goblet cells elicits an increase in MUC5AC mRNA and by identifying beta-CM-7 in the blood of asthmatic patients. This association may not necessarily be simply cause and effect as the person has to be consuming A1 milk, beta-CM-7 must pass into the systemic circulation and the tissues have to be actively inflamed. These prerequisites could explain why only a subgroup of the population, who have increased respiratory tract mucus production, find that many of their symptoms, including asthma, improve on a dairy elimination diet. (c) 2009 Elsevier Ltd. All rights reserved.

  4. Integrated outages increase Surry's availability

    International Nuclear Information System (INIS)

    Harms, S.R.; Downs, J.L.

    1995-01-01

    This article describes how, through Virginia Power's and Westinghouse's goal-oriented planning philosophy, teamwork and commitment, average outage duration has decreased significantly. During the past 10 years Virginia Power and its nuclear steam supply system (NSSS) services vendor, Westinghouse Electric Corp., have developed a working partnership with one goal in mind: increasing the availability and capacity factors of the North Anna and Surry nuclear power stations while driving down the operating costs of the plants. The outage integration program, steam generator maintenance agreement (SGMA), and integrated radiological services program form the core of this relationship and helped Virginia Power complete one of the most successful outages in Surry Power Station's operating history

  5. Environmental measures in forest. Realistic measures for counteracting negative effects of acid precipitation in forest; Miljoetiltak i skog. Realistiske tiltak for aa motvirke negative effekter av sur nedboer i skog

    Energy Technology Data Exchange (ETDEWEB)

    Nilsen, P [Norsk Inst. for Skogforskning, Aas (Norway)

    1996-01-01

    The conference paper deals with an Norwegian research programme concerning environmental measures for decreasing the effects of acidification in forest areas. This programme, which lasts in a period of five years, will terminate in 1997. An important part of the programme has been to investigate other types of measures than the ordinary methods of liming and fertilizing. In the course of the programme, there was determined to put the attention to the increased use of broad-leaved trees as an alternative in a coniferous forest. 19 refs., 1 fig.

  6. Implications of increased ethanol production

    International Nuclear Information System (INIS)

    1992-06-01

    The implications of increased ethanol production in Canada, assuming a 10% market penetration of a 10% ethanol/gasoline blend, are evaluated. Issues considered in the analysis include the provision of new markets for agricultural products, environmental sustainability, energy security, contribution to global warming, potential government cost (subsidies), alternative options to ethanol, energy efficiency, impacts on soil and water of ethanol crop production, and acceptance by fuel marketers. An economic analysis confirms that ethanol production from a stand-alone plant is not economic at current energy values. However, integration of ethanol production with a feedlot lowers the break-even price of ethanol by about 35 cents/l, and even further reductions could be achieved as technology to utilize lignocellulosic feedstock is commercialized. Ethanol production could have a positive impact on farm income, increasing cash receipts to grain farmers up to $53 million. The environmental impact of ethanol production from grain would be similar to that from crop production in general. Some concerns about ethanol/gasoline blends from the fuel industry have been reduced as those blends are now becoming recommended in some automotive warranties. However, the concerns of the larger fuel distributors are a serious constraint on an expansion of ethanol use. The economics of ethanol use could be improved by extending the federal excise tax exemption now available for pure alcohol fuels to the alcohol portion of alcohol/gasoline blends. 9 refs., 10 tabs

  7. Social Power Increases Interoceptive Accuracy

    Directory of Open Access Journals (Sweden)

    Mehrad Moeini-Jazani

    2017-08-01

    Full Text Available Building on recent psychological research showing that power increases self-focused attention, we propose that having power increases accuracy in perception of bodily signals, a phenomenon known as interoceptive accuracy. Consistent with our proposition, participants in a high-power experimental condition outperformed those in the control and low-power conditions in the Schandry heartbeat-detection task. We demonstrate that the effect of power on interoceptive accuracy is not explained by participants’ physiological arousal, affective state, or general intention for accuracy. Rather, consistent with our reasoning that experiencing power shifts attentional resources inward, we show that the effect of power on interoceptive accuracy is dependent on individuals’ chronic tendency to focus on their internal sensations. Moreover, we demonstrate that individuals’ chronic sense of power also predicts interoceptive accuracy similar to, and independent of, how their situationally induced feeling of power does. We therefore provide further support on the relation between power and enhanced perception of bodily signals. Our findings offer a novel perspective–a psychophysiological account–on how power might affect judgments and behavior. We highlight and discuss some of these intriguing possibilities for future research.

  8. Ego involvement increases doping likelihood.

    Science.gov (United States)

    Ring, Christopher; Kavussanu, Maria

    2018-08-01

    Achievement goal theory provides a framework to help understand how individuals behave in achievement contexts, such as sport. Evidence concerning the role of motivation in the decision to use banned performance enhancing substances (i.e., doping) is equivocal on this issue. The extant literature shows that dispositional goal orientation has been weakly and inconsistently associated with doping intention and use. It is possible that goal involvement, which describes the situational motivational state, is a stronger determinant of doping intention. Accordingly, the current study used an experimental design to examine the effects of goal involvement, manipulated using direct instructions and reflective writing, on doping likelihood in hypothetical situations in college athletes. The ego-involving goal increased doping likelihood compared to no goal and a task-involving goal. The present findings provide the first evidence that ego involvement can sway the decision to use doping to improve athletic performance.

  9. Propofol directly increases tau phosphorylation.

    Directory of Open Access Journals (Sweden)

    Robert A Whittington

    2011-01-01

    Full Text Available In Alzheimer's disease (AD and other tauopathies, the microtubule-associated protein tau can undergo aberrant hyperphosphorylation potentially leading to the development of neurofibrillary pathology. Anesthetics have been previously shown to induce tau hyperphosphorylation through a mechanism involving hypothermia-induced inhibition of protein phosphatase 2A (PP2A activity. However, the effects of propofol, a common clinically used intravenous anesthetic, on tau phosphorylation under normothermic conditions are unknown. We investigated the effects of a general anesthetic dose of propofol on levels of phosphorylated tau in the mouse hippocampus and cortex under normothermic conditions. Thirty min following the administration of propofol 250 mg/kg i.p., significant increases in tau phosphorylation were observed at the AT8, CP13, and PHF-1 phosphoepitopes in the hippocampus, as well as at AT8, PHF-1, MC6, pS262, and pS422 epitopes in the cortex. However, we did not detect somatodendritic relocalization of tau. In both brain regions, tau hyperphosphorylation persisted at the AT8 epitope 2 h following propofol, although the sedative effects of the drug were no longer evident at this time point. By 6 h following propofol, levels of phosphorylated tau at AT8 returned to control levels. An initial decrease in the activity and expression of PP2A were observed, suggesting that PP2A inhibition is at least partly responsible for the hyperphosphorylation of tau at multiple sites following 30 min of propofol exposure. We also examined tau phosphorylation in SH-SY5Y cells transfected to overexpress human tau. A 1 h exposure to a clinically relevant concentration of propofol in vitro was also associated with tau hyperphosphorylation. These findings suggest that propofol increases tau phosphorylation both in vivo and in vitro under normothermic conditions, and further studies are warranted to determine the impact of this anesthetic on the acceleration of

  10. Aag Hypoxanthine-DNA Glycosylase Is Synthesized in the Forespore Compartment and Involved in Counteracting the Genotoxic and Mutagenic Effects of Hypoxanthine and Alkylated Bases in DNA during Bacillus subtilis Sporulation.

    Science.gov (United States)

    Ayala-García, Víctor M; Valenzuela-García, Luz I; Setlow, Peter; Pedraza-Reyes, Mario

    2016-12-15

    Aag from Bacillus subtilis has been implicated in in vitro removal of hypoxanthine and alkylated bases from DNA. The regulation of expression of aag in B. subtilis and the resistance to genotoxic agents and mutagenic properties of an Aag-deficient strain were studied here. A strain with a transcriptional aag-lacZ fusion expressed low levels of β-galactosidase during growth and early sporulation but exhibited increased transcription during late stages of this developmental process. Notably, aag-lacZ expression was higher inside the forespore than in the mother cell compartment, and this expression was abolished in a sigG-deficient background, suggesting a forespore-specific mechanism of aag transcription. Two additional findings supported this suggestion: (i) expression of an aag-yfp fusion was observed in the forespore, and (ii) in vivo mapping of the aag transcription start site revealed the existence of upstream regulatory sequences possessing homology to σ G -dependent promoters. In comparison with the wild-type strain, disruption of aag significantly reduced survival of sporulating B. subtilis cells following nitrous acid or methyl methanesulfonate treatments, and the Rif r mutation frequency was significantly increased in an aag strain. These results suggest that Aag protects the genome of developing B. subtilis sporangia from the cytotoxic and genotoxic effects of base deamination and alkylation. In this study, evidence is presented revealing that aag, encoding a DNA glycosylase implicated in processing of hypoxanthine and alkylated DNA bases, exhibits a forespore-specific pattern of gene expression during B. subtilis sporulation. Consistent with this spatiotemporal mode of expression, Aag was found to protect the sporulating cells of this microorganism from the noxious and mutagenic effects of base deamination and alkylation. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  11. Neuropeptide S overcomes short term memory deficit induced by sleep restriction by increasing prefrontal cortex activity.

    Science.gov (United States)

    Thomasson, Julien; Canini, Frédéric; Poly-Thomasson, Betty; Trousselard, Marion; Granon, Sylvie; Chauveau, Frédéric

    2017-12-01

    Sleep restriction (SR) impairs short term memory (STM) that might be related to different processes. Neuropeptide S (NPS), an endogenous neuropeptide that improves short term memory, activates arousal and decreases anxiety is likely to counteract the SR-induced impairment of STM. The objective of the present study was to find common cerebral pathways in sleep restriction and NPS action in order to ultimately antagonize SR effect on memory. The STM was assessed using a spontaneous spatial alternation task in a T-maze. C57-Bl/6J male mice were distributed in 4 groups according to treatment (0.1nmol of NPS or vehicle intracerebroventricular injection) and to 20h-SR. Immediately after behavioural testing, regional c-fos immunohistochemistry was performed and used as a neural activation marker for spatial short term memory (prefrontal cortex, dorsal hippocampus) and emotional reactivity (basolateral amygdala and ventral hippocampus). Anxiety-like behaviour was assessed using elevated-plus maze task. Results showed that SR impaired short term memory performance and decreased neuronal activation in cingular cortex.NPS injection overcame SR-induced STM deficits and increased neuronal activation in infralimbic cortex. SR spared anxiety-like behavior in the elevated-plus maze. Neural activation in basolateral nucleus of amygdala and ventral hippocampus were not changed after SR.In conclusion, the present study shows that NPS overcomes SR-induced STM deficits by increasing prefrontal cortex activation independently of anxiety-like behaviour. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Adaptive aneuploidy protects against thiol peroxidase deficiency by increasing respiration via key mitochondrial proteins.

    Science.gov (United States)

    Kaya, Alaattin; Gerashchenko, Maxim V; Seim, Inge; Labarre, Jean; Toledano, Michel B; Gladyshev, Vadim N

    2015-08-25

    Aerobic respiration is a fundamental energy-generating process; however, there is cost associated with living in an oxygen-rich environment, because partially reduced oxygen species can damage cellular components. Organisms evolved enzymes that alleviate this damage and protect the intracellular milieu, most notably thiol peroxidases, which are abundant and conserved enzymes that mediate hydrogen peroxide signaling and act as the first line of defense against oxidants in nearly all living organisms. Deletion of all eight thiol peroxidase genes in yeast (∆8 strain) is not lethal, but results in slow growth and a high mutation rate. Here we characterized mechanisms that allow yeast cells to survive under conditions of thiol peroxidase deficiency. Two independent ∆8 strains increased mitochondrial content, altered mitochondrial distribution, and became dependent on respiration for growth but they were not hypersensitive to H2O2. In addition, both strains independently acquired a second copy of chromosome XI and increased expression of genes encoded by it. Survival of ∆8 cells was dependent on mitochondrial cytochrome-c peroxidase (CCP1) and UTH1, present on chromosome XI. Coexpression of these genes in ∆8 cells led to the elimination of the extra copy of chromosome XI and improved cell growth, whereas deletion of either gene was lethal. Thus, thiol peroxidase deficiency requires dosage compensation of CCP1 and UTH1 via chromosome XI aneuploidy, wherein these proteins support hydroperoxide removal with the reducing equivalents generated by the electron transport chain. To our knowledge, this is the first evidence of adaptive aneuploidy counteracting oxidative stress.

  13. Dividing Attention Increases Operational Momentum

    Directory of Open Access Journals (Sweden)

    Koleen McCrink

    2017-12-01

    Full Text Available When adding or subtracting two quantities, adults often compute an estimated outcome that is larger or smaller, respectively, than the actual outcome, a bias referred to as “operational momentum”. The effects of attention on operational momentum were investigated. Participants viewed a display in which two arrays of objects were added, or one array was subtracted from another array, and judged whether a subsequent outcome (probe array contained the correct or incorrect number of objects. In a baseline condition, only the arrays to be added or subtracted were viewed. In divided attention conditions, participants simultaneously viewed a sequence of colors or shapes, and judged which color (a non-spatial judgment or shape (a spatial judgment was repeated. Operational momentum occurred in all conditions, but was higher in divided attention conditions than in the baseline condition, primarily for addition problems. This pattern suggests that dividing attention, rather than decreasing operational momentum by decreasing attentional shifts, actually increased operational momentum. These results are consistent with a heightened use of arithmetic heuristics under conditions of divided attention.

  14. Job stress and productivity increase.

    Science.gov (United States)

    Adaramola, Samson Sunday

    2012-01-01

    This paper examines mental and physical pressures that workers bear at work. The authors discuss how on the-job stress affects a person's capabilities and productivity, and how such pressures lend to higher incidences of accidents at work. The paper also discuss methods of reducing job-related stress and increasing productivity. An intervention was conducted amongst workers in a private firm. It shows mental and emotional pressure can affect performance and productivity of a worker on the job. One of the biggest influences of today's worker is on the-job stress. Job stress occurs when the requirements of the job do not match the capabilities, resources, or needs of the worker. This consequently affects how a person would normally deal with customer service problems, grievances, violence, conflict, and decisions on the job. Stress is an inevitable part of everyday life, and is therefore a distinct part of a person's job. To properly control the outcome of stress, there are certain precautions and methods that should be taken that will boost productivity.

  15. Increasing Possibilities of Nano suspension

    International Nuclear Information System (INIS)

    Sutradhar, K.B.; Khatun, S.; Luna, I.P.

    2013-01-01

    Nowadays, a very large proportion of new drug candidates emerging from drug discovery programmes are water insoluble and thus poorly bioavailable. To avoid this problem, nano technology for drug delivery has gained much interest as a way to improve the solubility problems. Nano refers to particles size range of 1-1000 nm. The reduction of drug particles into the submicron range leads to a significant increase in the dissolution rate and therefore enhances bioavailability. Nanosuspensions are part of nano technology. This interacts with the body at subcellular (i.e., molecular) scales with a high degree of specificity and can be potentially translated into targeted cellular and tissue-specific clinical applications designed to achieve maximal therapeutic efficacy with minimal side effects. Production of drugs as nanosuspensions can be developed for drug delivery systems as an oral formulation and no noral administration. Here, this review describes the methods of pharmaceutical nano suspension production including advantages and disadvantages, potential benefits, characterization tests, and pharmaceutical applications in drug delivery

  16. Turkey's Increasing Role in Afghanistan

    Directory of Open Access Journals (Sweden)

    Muharrem Eksi

    2010-07-01

    Full Text Available This paper is briefly dealing with the current situation in Afghanistan within the context of Turkey’s increasing role in Afghanistan. Turkish-Afghani relations are examined in terms of politics and economy while Turkish foreign policies towards Afghanistan and the Turkish-Pakistani-Afghani triple summit attempts are analyzed. Additionally, Turkey’s security and socio-economic contributions in Afghanistan are emphasized. Turkey’s unwillingness to send troops to Afghanistanfor operational purposes that is frequently debated in national and international circles has been evaluated by stating the advantages and disadvantages of such decision. Turkey’s quiet approach between 2001 and 2004 towards Afghanistan, which have been energizing since 2005 and Foreign Minister Ahmet Davutoğlu’s visit to Afghanistan on June 2009 have been dealt as well. By considering Davutoglu’s policies, aiming to introduce Turkey as a global actor and as the term President of the UNSC (the UN Security Council, it seems that Turkey is preparing to play a more active role in Afghanistan.

  17. Scientific progress as increasing verisimilitude.

    Science.gov (United States)

    Niiniluoto, Ilkka

    2014-06-01

    According to the foundationalist picture, shared by many rationalists and positivist empiricists, science makes cognitive progress by accumulating justified truths. Fallibilists, who point out that complete certainty cannot be achieved in empirical science, can still argue that even successions of false theories may progress toward the truth. This proposal was supported by Karl Popper with his notion of truthlikeness or verisimilitude. Popper's own technical definition failed, but the idea that scientific progress means increasing truthlikeness can be expressed by defining degrees of truthlikeness in terms of similarities between states of affairs. This paper defends the verisimilitude approach against Alexander Bird who argues that the "semantic" definition (in terms of truth or truthlikeness alone) is not sufficient to define progress, but the "epistemic" definition referring to justification and knowledge is more adequate. Here Bird ignores the crucial distinction between real progress and estimated progress, explicated by the difference between absolute (and usually unknown) degrees of truthlikeness and their evidence-relative expected values. Further, it is argued that Bird's idea of returning to the cumulative model of growth requires an implausible trick of transforming past false theories into true ones.

  18. Laboratory facilities increased by gifts

    International Nuclear Information System (INIS)

    1968-01-01

    As a result of gifts from two Member States facilities at the Agency's research centre at Seibersdorf, Austria, have been increased. New equipment has been provided by France and Romania. The French equipment is a coincidence counter to be operated in conjunction with a computer and is valued at $35 000. It can give automatically an exact measurement of radioactivity in a chemical solution containing radioisotopes. This means that a sample of the solution can be sent to another laboratory to be used for calibrating instruments and checking results of research work. Since 1963 nearly 8 000 radioactive solutions to be used as standards have been sent from Seibersdorf to research laboratories and hospitals in 56 countries. The demand continues to grow, and in order to meet it the equipment was developed by the Saclay Research Centre of the Commissariat a l'Energie Atomique in collaboration with Seibersdorf. From Romania have come six electronic measuring instruments worth $6 000 to assist nuclear research, surveying and prospecting. Three are electronic scalers for experimental work involving the counting of radioactive emissions, and three are survey meters for detecting the presence of radioactivity in geological samples. (author)

  19. Identification of human ferritin, heavy polypeptide 1 (FTH1) and yeast RGI1 (YER067W) as pro-survival sequences that counteract the effects of Bax and copper in Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Eid, Rawan [Department of Chemistry and Chemical Engineering, Royal Military College, Kingston, Ontario (Canada); Department of Biology, Queen' s University, Kingston, Ontario (Canada); Boucher, Eric [Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec (Canada); Gharib, Nada [Department of Chemistry and Chemical Engineering, Royal Military College, Kingston, Ontario (Canada); Khoury, Chamel [Department of Chemistry and Chemical Engineering, Royal Military College, Kingston, Ontario (Canada); Department of Biology, Queen' s University, Kingston, Ontario (Canada); Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec (Canada); Arab, Nagla T.T. [Department of Chemistry and Chemical Engineering, Royal Military College, Kingston, Ontario (Canada); Department of Biology, Queen' s University, Kingston, Ontario (Canada); Murray, Alistair [Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec (Canada); Young, Paul G. [Department of Biology, Queen' s University, Kingston, Ontario (Canada); Mandato, Craig A. [Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec (Canada); Greenwood, Michael T., E-mail: michael.greenwood@rmc.ca [Department of Chemistry and Chemical Engineering, Royal Military College, Kingston, Ontario (Canada)

    2016-03-01

    Ferritin is a sub-family of iron binding proteins that form multi-subunit nanotype iron storage structures and prevent oxidative stress induced apoptosis. Here we describe the identification and characterization of human ferritin, heavy polypeptide 1 (FTH1) as a suppressor of the pro-apoptotic murine Bax sequence in yeast. In addition we demonstrate that FTH1 is a general pro-survival sequence since it also prevents the cell death inducing effects of copper when heterologously expressed in yeast. Although ferritins are phylogenetically widely distributed and are present in most species of Bacteria, Archaea and Eukarya, ferritin is conspicuously absent in most fungal species including Saccharomyces cerevisiae. An in silico analysis of the yeast proteome lead to the identification of the 161 residue RGI1 (YER067W) encoded protein as a candidate for being a yeast ferritin. In addition to sharing 20% sequence identity with the 183 residue FTH1, RGI1 also has similar pro-survival properties as ferritin when overexpressed in yeast. Analysis of recombinant protein by SDS-PAGE and by electron microscopy revealed the expected formation of higher-order structures for FTH1 that was not observed with Rgi1p. Further analysis revealed that cells overexpressing RGI1 do not show increased resistance to iron toxicity and do not have enhanced capacity to store iron. In contrast, cells lacking RGI1 were found to be hypersensitive to the toxic effects of iron. Overall, our results suggest that Rgi1p is a novel pro-survival protein whose function is not related to ferritin but nevertheless it may have a role in regulating yeast sensitivity to iron stress. - Highlights: • Human ferritin, heavy polypeptide 1 (FTH1) was identified as a suppressor of the pro-apoptotic Bax in yeast. • Based on its similarity to ferritin we examined Rgi1p/YER067W for potential ferritin like functions. • Like human H-ferritin, RGI1 confers increased resistance to apoptotic inducing stresses in yeast.

  20. Identification of human ferritin, heavy polypeptide 1 (FTH1) and yeast RGI1 (YER067W) as pro-survival sequences that counteract the effects of Bax and copper in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Eid, Rawan; Boucher, Eric; Gharib, Nada; Khoury, Chamel; Arab, Nagla T.T.; Murray, Alistair; Young, Paul G.; Mandato, Craig A.; Greenwood, Michael T.

    2016-01-01

    Ferritin is a sub-family of iron binding proteins that form multi-subunit nanotype iron storage structures and prevent oxidative stress induced apoptosis. Here we describe the identification and characterization of human ferritin, heavy polypeptide 1 (FTH1) as a suppressor of the pro-apoptotic murine Bax sequence in yeast. In addition we demonstrate that FTH1 is a general pro-survival sequence since it also prevents the cell death inducing effects of copper when heterologously expressed in yeast. Although ferritins are phylogenetically widely distributed and are present in most species of Bacteria, Archaea and Eukarya, ferritin is conspicuously absent in most fungal species including Saccharomyces cerevisiae. An in silico analysis of the yeast proteome lead to the identification of the 161 residue RGI1 (YER067W) encoded protein as a candidate for being a yeast ferritin. In addition to sharing 20% sequence identity with the 183 residue FTH1, RGI1 also has similar pro-survival properties as ferritin when overexpressed in yeast. Analysis of recombinant protein by SDS-PAGE and by electron microscopy revealed the expected formation of higher-order structures for FTH1 that was not observed with Rgi1p. Further analysis revealed that cells overexpressing RGI1 do not show increased resistance to iron toxicity and do not have enhanced capacity to store iron. In contrast, cells lacking RGI1 were found to be hypersensitive to the toxic effects of iron. Overall, our results suggest that Rgi1p is a novel pro-survival protein whose function is not related to ferritin but nevertheless it may have a role in regulating yeast sensitivity to iron stress. - Highlights: • Human ferritin, heavy polypeptide 1 (FTH1) was identified as a suppressor of the pro-apoptotic Bax in yeast. • Based on its similarity to ferritin we examined Rgi1p/YER067W for potential ferritin like functions. • Like human H-ferritin, RGI1 confers increased resistance to apoptotic inducing stresses in yeast.

  1. Dioxin-induced acute cardiac mitochondrial oxidative damage and increased activity of ATP-sensitive potassium channels in Wistar rats

    International Nuclear Information System (INIS)

    Pereira, Susana P.; Pereira, Gonçalo C.; Pereira, Cláudia V.; Carvalho, Filipa S.; Cordeiro, Marília H.; Mota, Paula C.; Ramalho-Santos, João; Moreno, António J.; Oliveira, Paulo J.

    2013-01-01

    The environmental dioxin 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is classified as a Group 1 human carcinogen and teratogenic agent. We hypothesize that TCDD-induced oxidative stress may also interfere with mitochondrial ATP-sensitive potassium channels (mitoKATP), which are known to regulate and to be regulated by mitochondrial redox state. We investigated the effects of an acute treatment of male Wistar rats with TCDD (50 μg/kg i.p.) and measured the regulation of cardiac mitoKATP. While the function of cardiac mitochondria was slightly depressed, mitoKATP activity was 52% higher in animals treated with TCDD. The same effects were not observed in liver mitochondria isolated from the same animals. Our data also shows that regulation of mitochondrial ROS production by mitoKATP activity is different in both groups. To our knowledge, this is the first report to show that TCDD increases mitoKATP activity in the heart, which may counteract the increased oxidative stress caused by the dioxin during acute exposure. -- Highlights: •Acute TCDD treatment of Wistar rats causes cardiac oxidative stress. •Acute TCDD treatment causes cardiac mitochondrial alterations. •Mitochondrial liver vs. heart alterations are distinct. •TCDD treatment resulted in altered activity of cardiac mitochondrial K-ATP channels. -- Dioxin alters the regulation of cardiac mitochondrial ATP-sensitive potassium channels and disturbs mitochondrial physiology

  2. Evolution of increased competitiveness in cows trades off with reduced milk yield, fertility and more masculine morphology.

    Science.gov (United States)

    Sartori, Cristina; Mazza, Serena; Guzzo, Nadia; Mantovani, Roberto

    2015-08-01

    In some species females compete for food, foraging territories, mating, and nesting sites. Competing females can exhibit morphological, physiological, and behavioral adaptations typical of males, which are commonly considered as secondary sexual traits. Competition and the development of traits increasing competitiveness require much energy and may exert adverse effects on fecundity and survival. From an evolutionary perspective, positive selection for increased competitiveness would then result in evolution of reduced values for traits related to fitness such as fecundity and survival. There is recent evidence for such evolutionary trade-offs involving male competition, but no study has considered competing females so far. Using data from competitions for dominance in cows (Bos taurus), we found negative genetic correlations between traits providing success in competition, that is, fighting ability and fitness traits related to milk production and with fertility (the inverse of parity-conception interval). Fighting ability also showed low but positive genetic correlations with "masculine" morphological traits, and negative correlations with "feminine" traits. A genetic change in traits over time has occurred due to selection on competitiveness, corresponding to an evolutionary process of "masculinization" counteracting the official selection for milk yield. Similar evolutionary trade-off between success in competition and fitness components may be present in various species experiencing female competition. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  3. Antioxidative Diet Supplementation Reverses High-Fat Diet-Induced Increases of Cardiovascular Risk Factors in Mice

    Directory of Open Access Journals (Sweden)

    Hilda Vargas-Robles

    2015-01-01

    Full Text Available Obesity is a worldwide epidemic that is characterized not only by excessive fat deposition but also by systemic microinflammation, high oxidative stress, and increased cardiovascular risk factors. While diets enriched in natural antioxidants showed beneficial effects on oxidative stress, blood pressure, and serum lipid composition, diet supplementation with synthetic antioxidants showed contradictive results. Thus, we tested in C57Bl/6 mice whether a daily dosage of an antioxidative mixture consisting of vitamin C, vitamin E, L-arginine, eicosapentaenoic acid, and docosahexaenoic acid (corabion would affect cardiovascular risk factors associated with obesity. Obese mice showed increased serum triglyceride and glucose levels and hypertension after eight weeks of being fed a high-fat diet (HFD. Importantly, corabion ameliorated all of these symptoms significantly. Oxidative stress and early signs of systemic microinflammation already developed after two weeks of high-fat diet and were significantly reduced by daily doses of corabion. Of note, the beneficial effects of corabion could not be observed when applying its single antioxidative components suggesting that a combination of various nutrients is required to counteract HFD-induced cardiovascular risk factors. Thus, daily consumption of corabion may be beneficial for the management of obesity-related cardiovascular complications.

  4. Noncommunicable Diseases: Three Decades Of Global Data Show A Mixture Of Increases And Decreases In Mortality Rates.

    Science.gov (United States)

    Ali, Mohammed K; Jaacks, Lindsay M; Kowalski, Alysse J; Siegel, Karen R; Ezzati, Majid

    2015-09-01

    Noncommunicable diseases are the leading health concerns of the modern era, accounting for two-thirds of global deaths, half of all disability, and rapidly growing costs. To provide a contemporary overview of the burdens caused by noncommunicable diseases, we compiled mortality data reported by authorities in forty-nine countries for atherosclerotic cardiovascular diseases; diabetes; chronic respiratory diseases; and lung, colon, breast, cervical, liver, and stomach cancers. From 1980 to 2012, on average across all countries, mortality for cardiovascular disease, stomach cancer, and cervical cancer declined, while mortality for diabetes, liver cancer, and female chronic respiratory disease and lung cancer increased. In contrast to the relatively steep cardiovascular and cancer mortality declines observed in high-income countries, mortality for cardiovascular disease and chronic respiratory disease was flat in most low- and middle-income countries, which also experienced increasing breast and colon cancer mortality. These divergent mortality patterns likely reflect differences in timing and magnitude of risk exposures, health care, and policies to counteract the diseases. Improving both the coverage and the accuracy of mortality documentation in populous low- and middle-income countries is a priority, as is the need to rigorously evaluate societal-level interventions. Furthermore, given the complex, chronic, and progressive nature of noncommunicable diseases, policies and programs to prevent and control them need to be multifaceted and long-term, as returns on investment accrue with time. Project HOPE—The People-to-People Health Foundation, Inc.

  5. Up-regulated Ectonucleotidases in Fas-Associated Death Domain Protein- and Receptor-Interacting Protein Kinase 1-Deficient Jurkat Leukemia Cells Counteract Extracellular ATP/AMP Accumulation via Pannexin-1 Channels during Chemotherapeutic Drug-Induced Apoptosis.

    Science.gov (United States)

    Boyd-Tressler, Andrea M; Lane, Graham S; Dubyak, George R

    2017-07-01

    Pannexin-1 (Panx1) channels mediate the efflux of ATP and AMP from cancer cells in response to induction of extrinsic apoptosis by death receptors or intrinsic apoptosis by chemotherapeutic agents. We previously described the accumulation of extracellular ATP /AMP during chemotherapy-induced apoptosis in Jurkat human leukemia cells. In this study, we compared how different signaling pathways determine extracellular nucleotide pools in control Jurkat cells versus Jurkat lines that lack the Fas-associated death domain (FADD) or receptor-interacting protein kinase 1 (RIP1) cell death regulatory proteins. Tumor necrosis factor- α induced extrinsic apoptosis in control Jurkat cells and necroptosis in FADD-deficient cells; treatment of both lines with chemotherapeutic drugs elicited similar intrinsic apoptosis. Robust extracellular ATP/AMP accumulation was observed in the FADD-deficient cells during necroptosis, but not during apoptotic activation of Panx1 channels. Accumulation of extracellular ATP/AMP was similarly absent in RIP1-deficient Jurkat cells during apoptotic responses to chemotherapeutic agents. Apoptotic activation triggered equivalent proteolytic gating of Panx1 channels in all three Jurkat cell lines. The differences in extracellular ATP/AMP accumulation correlated with cell-line-specific expression of ectonucleotidases that metabolized the released ATP/AMP. CD73 mRNA, and α β -methylene-ADP-inhibitable ecto-AMPase activity were elevated in the FADD-deficient cells. In contrast, the RIP1-deficient cells were defined by increased expression of tartrate-sensitive prostatic acid phosphatase as a broadly acting ectonucleotidase. Thus, extracellular nucleotide accumulation during regulated tumor cell death involves interplay between ATP/AMP efflux pathways and different cell-autonomous ectonucleotidases. Differential expression of particular ectonucleotidases in tumor cell variants will determine whether chemotherapy-induced activation of Panx1 channels

  6. Tricyclic antidepressant amitriptyline indirectly increases the proliferation of adult dentate gyrus-derived neural precursors: an involvement of astrocytes.

    Directory of Open Access Journals (Sweden)

    Shuken Boku

    Full Text Available Antidepressants increase the proliferation of neural precursors in adult dentate gyrus (DG, which is considered to be involved in the therapeutic action of antidepressants. However, the mechanism underlying it remains unclear. By using cultured adult rat DG-derived neural precursors (ADP, we have already shown that antidepressants have no direct effects on ADP. Therefore, antidepressants may increase the proliferation of neural precursors in adult DG via unknown indirect mechanism. We have also shown that amitriptyline (AMI, a tricyclic antidepressant, induces the expressions of GDNF, BDNF, FGF2 and VEGF, common neurogenic factors, in primary cultured astrocytes (PCA. These suggest that AMI-induced factors in astrocytes may increase the proliferation of neural precursors in adult DG. To test this hypothesis, we examined the effects of AMI-induced factors and conditioned medium (CM from PCA treated with AMI on ADP proliferation. The effects of CM and factors on ADP proliferation were examined with BrdU immunocytochemistry. AMI had no effect on ADP proliferation, but AMI-treated CM increased it. The receptors of GDNF, BDNF and FGF2, but not VEGF, were expressed in ADP. FGF2 significantly increased ADP proliferation, but not BDNF and GDNF. In addition, both of a specific inhibitor of FGF receptors and anti-FGF2 antibody significantly counteracted the increasing effect of CM on ADP proliferation. In addition, FGF2 in brain is mainly derived from astrocytes that are key components of the neurogenic niches in adult DG. These suggest that AMI may increase ADP proliferation indirectly via PCA and that FGF2 may a potential candidate to mediate such an indirect effect of AMI on ADP proliferation via astrocytes.

  7. The increasing burden of depression

    Directory of Open Access Journals (Sweden)

    Lépine J-P

    2011-05-01

    Full Text Available Jean-Pierre Lépine1, Mike Briley21Hôpital Lariboisière Fernand Widal, Assistance Publique Hôpitaux de Paris Unité INSERM 705 CNRS UMR 8206, Université Paris Diderot, Paris, France; 2NeuroBiz Consulting and Communication, Castres, FranceAbstract: Recent epidemiological surveys conducted in general populations have found that the lifetime prevalence of depression is in the range of 10% to 15%. Mood disorders, as defined by the World Mental Health and the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, have a 12-month prevalence which varies from 3% in Japan to over 9% in the US. A recent American survey found the prevalence of current depression to be 9% and the rate of current major depression to be 3.4%. All studies of depressive disorders have stressed the importance of the mortality and morbidity associated with depression. The mortality risk for suicide in depressed patients is more than 20-fold greater than in the general population. Recent studies have also shown the importance of depression as a risk factor for cardiovascular death. The risk of cardiac mortality after an initial myocardial infarction is greater in patients with depression and related to the severity of the depressive episode. Greater severity of depressive symptoms has been found to be associated with significantly higher risk of all-cause mortality including cardiovascular death and stroke. In addition to mortality, functional impairment and disability associated with depression have been consistently reported. Depression increases the risk of decreased workplace productivity and absenteeism resulting in lowered income or unemployment. Absenteeism and presenteeism (being physically present at work but functioning suboptimally have been estimated to result in a loss of $36.6 billion per year in the US. Worldwide projections by the World Health Organization for the year 2030 identify unipolar major depression as the leading cause of disease burden

  8. Climate change-induced vegetation shifts lead to more ecological droughts despite projected rainfall increases in many global temperate drylands.

    Science.gov (United States)

    Tietjen, Britta; Schlaepfer, Daniel R; Bradford, John B; Lauenroth, William K; Hall, Sonia A; Duniway, Michael C; Hochstrasser, Tamara; Jia, Gensuo; Munson, Seth M; Pyke, David A; Wilson, Scott D

    2017-07-01

    Drylands occur worldwide and are particularly vulnerable to climate change because dryland ecosystems depend directly on soil water availability that may become increasingly limited as temperatures rise. Climate change will both directly impact soil water availability and change plant biomass, with resulting indirect feedbacks on soil moisture. Thus, the net impact of direct and indirect climate change effects on soil moisture requires better understanding. We used the ecohydrological simulation model SOILWAT at sites from temperate dryland ecosystems around the globe to disentangle the contributions of direct climate change effects and of additional indirect, climate change-induced changes in vegetation on soil water availability. We simulated current and future climate conditions projected by 16 GCMs under RCP 4.5 and RCP 8.5 for the end of the century. We determined shifts in water availability due to climate change alone and due to combined changes of climate and the growth form and biomass of vegetation. Vegetation change will mostly exacerbate low soil water availability in regions already expected to suffer from negative direct impacts of climate change (with the two RCP scenarios giving us qualitatively similar effects). By contrast, in regions that will likely experience increased water availability due to climate change alone, vegetation changes will counteract these increases due to increased water losses by interception. In only a small minority of locations, climate change-induced vegetation changes may lead to a net increase in water availability. These results suggest that changes in vegetation in response to climate change may exacerbate drought conditions and may dampen the effects of increased precipitation, that is, leading to more ecological droughts despite higher precipitation in some regions. Our results underscore the value of considering indirect effects of climate change on vegetation when assessing future soil moisture conditions in water

  9. Climate change-induced vegetation shifts lead to more ecological droughts despite projected rainfall increases in many global temperate drylands

    Science.gov (United States)

    Tietjen, Britta; Schlaepfer, Daniel R.; Bradford, John B.; Laurenroth, William K.; Hall, Sonia A.; Duniway, Michael C.; Hochstrasser, Tamara; Jia, Gensuo; Munson, Seth M.; Pyke, David A.; Wilson, Scott D.

    2017-01-01

    Drylands occur world-wide and are particularly vulnerable to climate change since dryland ecosystems depend directly on soil water availability that may become increasingly limited as temperatures rise. Climate change will both directly impact soil water availability, and also change plant biomass, with resulting indirect feedbacks on soil moisture. Thus, the net impact of direct and indirect climate change effects on soil moisture requires better understanding.We used the ecohydrological simulation model SOILWAT at sites from temperate dryland ecosystems around the globe to disentangle the contributions of direct climate change effects and of additional indirect, climate change-induced changes in vegetation on soil water availability. We simulated current and future climate conditions projected by 16 GCMs under RCP 4.5 and RCP 8.5 for the end of the century. We determined shifts in water availability due to climate change alone and due to combined changes of climate and the growth form and biomass of vegetation.Vegetation change will mostly exacerbate low soil water availability in regions already expected to suffer from negative direct impacts of climate change (with the two RCP scenarios giving us qualitatively similar effects). By contrast, in regions that will likely experience increased water availability due to climate change alone, vegetation changes will counteract these increases due to increased water losses by interception. In only a small minority of locations, climate change induced vegetation changes may lead to a net increase in water availability. These results suggest that changes in vegetation in response to climate change may exacerbate drought conditions and may dampen the effects of increased precipitation, i.e. leading to more ecological droughts despite higher precipitation in some regions. Our results underscore the value of considering indirect effects of climate change on vegetation when assessing future soil moisture conditions in water

  10. Hyperglycemia induces memory impairment linked to increased acetylcholinesterase activity in zebrafish (Danio rerio).

    Science.gov (United States)

    Capiotti, Katiucia Marques; De Moraes, Daiani Almeida; Menezes, Fabiano Peres; Kist, Luiza Wilges; Bogo, Maurício Reis; Da Silva, Rosane Souza

    2014-11-01

    Diabetes mellitus, which causes hyperglycemia, affects the central nervous system and can impairs cognitive functions, such as memory. The aim of this study was to investigate the effects of hyperglycemia on memory as well as on the activity of acethylcholinesterase. Hyperglycemia was induced in adult zebrafish by immersion in glucose 111mM by 14 days. The animals were divided in 4 groups: control, glucose-treated, glucose-washout 7-days and glucose-washout 14-days. We evaluated the performance in inhibitory avoidance task and locomotor activity. We also determined acethylcholinesterase activity and gene expression from whole brain. In order to counteract the effect of hyperglycemia underlined by effects on acethylcholinesterase activity, we treated the animals with galantamine (0.05ng/g), an inhibitor of this enzyme. Also we evaluated the gene expression of insulin receptor and glucose transporter from zebrafish brain. The hyperglycemia promoted memory deficit in adult zebrafish, which can be explained by increased AChE activity. The ache mRNA levels from zebrafish brain were decrease in 111mM glucose group and returned to normal levels after 7 days of glucose withdrawal. Insulin receptors (insra-1, insra-2, insrb-1 and insrb-2) and glut-3 mRNA levels were not significantly changed. Our results also demonstrated that galantamine was able to reverse the memory deficit caused by hyperglycemia, demonstrating that these effects involve modulation of AChE activity. These data suggest that the memory impairment induced by hyperglycemia is underlined by the cholinergic dysfunction caused by the mechanisms involving the control of acetylcholinesterase function and gene expression. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Sex in murky waters: algal-induced turbidity increases sexual selection in pipefish.

    Science.gov (United States)

    Sundin, Josefin; Aronsen, Tonje; Rosenqvist, Gunilla; Berglund, Anders

    2017-01-01

    Algal-induced turbidity has been shown to alter several important aspects of reproduction and sexual selection. However, while turbidity has been shown to negatively affect reproduction and sexually selected traits in some species, it may instead enhance reproductive success in others, implying that the impact of eutrophication is far more complex than originally believed. In this study, we aimed to provide more insight into these inconsistent findings. We used molecular tools to investigate the impact of algal turbidity on reproductive success and sexual selection on males in controlled laboratory experiments, allowing mate choice, mating competition, and mate encounter rates to affect reproduction. As study species, we used the broad-nosed pipefish, Syngnathus typhle , a species practicing male pregnancy and where we have previously shown that male mate choice is impaired by turbidity. Here, turbidity instead enhanced sexual selection on male size and mating success as well as reproductive success. Effects from mating competition and mate encounter rates may thus override effects from mate choice based on visual cues, producing an overall stronger sexual selection in turbid waters. Hence, seemingly inconsistent effects of turbidity on sexual selection may depend on which mechanisms of sexual selection that have been under study. Algal blooms are becoming increasingly more common due to eutrophication of freshwater and marine environments. The high density of algae lowers water transparency and reduces the possibility for fish and other aquatic animals to perform behaviors dependent on vision. We have previously shown that pipefish are unable to select the best partner in mate choice trials when water transparency was reduced. However, fish might use other senses than vision to compensate for the reduction in water transparency. In this study, we found that when fish were allowed to freely interact, thereby allowing competition between partners and direct contact

  12. Increased storage and secretion of phosphatidylcholines by senescent human peritoneal mesothelial cells.

    Science.gov (United States)

    Bartosova, Maria; Rudolf, Andras; Pichl, Sebastian; Schmidt, Kathrin; Okun, Jürgen G; Straub, Beate K; Rutkowski, Rafael; Witowski, Janusz; Schmitt, Claus P

    2016-08-01

    Human peritoneal mesothelial cells (HPMC) secrete phosphatidylcholines (PC) which form a lipid bilayer lining the peritoneum. They prevent frictions and adhesions and act as a barrier to the transport of water-soluble solutes while permitting water flux. PC may play an essential role in peritoneal integrity and function, the role of PD induced HPMC senescence on PC homeostasis, however, is unknown. HPMC cell lines were isolated from four non-uremic patients. Expression of the three PC synthesis genes (rt-PCR), and cellular storage and secretion of PC (ESI-mass-spectrometry) were analyzed in young and senescent HPMC (>Hayflick-limit). Senescent cells displayed significantly altered morphology; flow cytometry demonstrated extensive staining for senescence-associated beta galactosidase. Nine different PC were detected in HPMC with palmitoyl-myristoyl phosphatidylcholine (PMPC) being most abundant. In senescent HPMC mRNA expression of the three key PC synthesis genes was 1.5-, 2.4- and 6-fold increased as compared to young HPMC, with the latter, phosphatidylcholine cytidylyltransferase, being rate limiting. Intracellular storage of the nine PC was 75-450 % higher in senescent vs. young HPMC, PC secretion rates were 100-300 % higher. Intracellular PC concentrations were not correlated with the PC secretion rates. Electron microscopy demonstrated lamellar bodies, the primary storage site of PC, in senescent but not in young cells. Senescent HPMC store and secrete substantially more PC than young cells. Our findings indicate a novel protective mechanism, which should counteract peritoneal damage induced by chronic exposure to PD fluids.

  13. PARP-1 expression is increased in colon adenoma and carcinoma and correlates with OGG1.

    Directory of Open Access Journals (Sweden)

    Tomasz Dziaman

    Full Text Available The ethiology of colon cancer is largely dependent on inflammation driven oxidative stress. The analysis of 8-oxodeoxyguanosine (8-oxodGuo level in leukocyte DNA of healthy controls (138 individuals, patients with benign adenomas (AD, 137 individuals and with malignant carcinomas (CRC, 169 individuals revealed a significant increase in the level of 8-oxodGuo in leukocyte DNA of AD and CRC patients in comparison to controls. The counteracting mechanism is base excision repair, in which OGG1 and PARP-1 play a key role. We investigated the level of PARP-1 and OGG1 mRNA and protein in diseased and marginal, normal tissues taken from AD and CRC patients and in leukocytes taken from the patients as well as from healthy subjects. In colon tumors the PARP-1 mRNA level was higher than in unaffected colon tissue and in polyp tissues. A high positive correlation was found between PARP-1 and OGG1 mRNA levels in all investigated tissues. This suggests reciprocal influence of PARP-1 and OGG1 on their expression and stability, and may contribute to progression of colon cancer. PARP-1 and OGG1 proteins level was several fold higher in polyps and CRC in comparison to normal colon tissues. Individuals bearing the Cys326Cys genotype of OGG1 were characterized by higher PARP-1 protein level in diseased tissues than the Ser326Cys and Ser326Ser genotypes. Aforementioned result may suggest that the diseased cells with polymorphic OGG1 recruit more PARP protein, which is necessary to remove 8-oxodGuo. Thus, patients with decreased activity of OGG1/polymorphism of the OGG1 gene and higher 8-oxodGuo level may be more susceptible to treatment with PARP-1 inhibitors.

  14. Short-term molecular acclimation processes of legume nodules to increased external oxygen concentration

    Directory of Open Access Journals (Sweden)

    Ulrike eAvenhaus

    2016-01-01

    Full Text Available Nitrogenase is an oxygen labile enzyme. Microaerobic conditions within the infected zone of nodules are maintained primarily by an oxygen diffusion barrier located in the nodule cortex. Flexibility of the oxygen diffusion barrier is important for the acclimation processes of nodules in response to changes in external oxygen concentration. The hypothesis of the present study was that there are additional molecular mechanisms involved. Nodule activity of Medicago truncatula plants were continuously monitored during a change from 21 to 25 or 30 % oxygen around root nodules by measuring nodule H2 evolution. Within about two minutes of the increase in oxygen concentration, a steep decline in nitrogenase activity occurred. A quick recovery commenced about eight minutes later. A qPCR-based analysis of the expression of genes for nitrogenase components showed a tendency towards upregulation during the recovery. The recovery resulted in a new constant activity after about 30 minutes, corresponding to approximately 90 % of the pre-treatment level. An RNAseq-based comparative transcriptome profiling of nodules at that point in time revealed that genes for nodule-specific cysteine-rich (NCR peptides, defensins, leghaemoglobin and chalcone and stilbene synthase were significantly upregulated when considered as a gene family. A gene for a nicotianamine synthase-like protein (Medtr1g084050 showed a strong increase in count number. The gene appears to be of importance for nodule functioning, as evidenced by its consistently high expression in nodules and a strong reaction to various environmental cues that influence nodule activity. A Tnt1-mutant that carries an insert in the coding sequence (cds of that gene showed reduced nitrogen fixation and less efficient acclimation to an increased external oxygen concentration. It was concluded that sudden increases in oxygen concentration around nodules destroy nitrogenase, which is quickly counteracted by an increased

  15. Increased VLDL in nephrotic patients results from a decreased catabolism while increased LDL results from increased synthesis

    NARCIS (Netherlands)

    de Sain-van der Velden, M; Kaysen, GA; Barrett, HA; Stellaard, F; Gadellaa, MM; Voorbij, HA; Reijngoud, DJ; Rabelink, TJ

    Increased very low density lipoprotein (VLDL) in nephrotic patients results from a decreased catabolism while increased low density lipoprotein (LDL) results from increased synthesis. Hyperlipidemias a hallmark of nephrotic syndrome that has been associated with increased risk for ischemic heart

  16. Spermidine Suppresses Age-Associated Memory Impairment by Preventing Adverse Increase of Presynaptic Active Zone Size and Release.

    Directory of Open Access Journals (Sweden)

    Varun K Gupta

    2016-09-01

    Full Text Available Memories are assumed to be formed by sets of synapses changing their structural or functional performance. The efficacy of forming new memories declines with advancing age, but the synaptic changes underlying age-induced memory impairment remain poorly understood. Recently, we found spermidine feeding to specifically suppress age-dependent impairments in forming olfactory memories, providing a mean to search for synaptic changes involved in age-dependent memory impairment. Here, we show that a specific synaptic compartment, the presynaptic active zone (AZ, increases the size of its ultrastructural elaboration and releases significantly more synaptic vesicles with advancing age. These age-induced AZ changes, however, were fully suppressed by spermidine feeding. A genetically enforced enlargement of AZ scaffolds (four gene-copies of BRP impaired memory formation in young animals. Thus, in the Drosophila nervous system, aging AZs seem to steer towards the upper limit of their operational range, limiting synaptic plasticity and contributing to impairment of memory formation. Spermidine feeding suppresses age-dependent memory impairment by counteracting these age-dependent changes directly at the synapse.

  17. The transient nature of Bunyamwera orthobunyavirus NSs protein expression: effects of increased stability of NSs protein on virus replication.

    Science.gov (United States)

    van Knippenberg, Ingeborg; Fragkoudis, Rennos; Elliott, Richard M

    2013-01-01

    The NSs proteins of bunyaviruses are the viral interferon antagonists, counteracting the host's antiviral response to infection. During high-multiplicity infection of cultured mammalian cells with Bunyamwera orthobunyavirus (BUNV), NSs is rapidly degraded after reaching peak levels of expression at 12hpi. Through the use of inhibitors this was shown to be the result of proteasomal degradation. A recombinant virus (rBUN4KR), in which all four lysine residues in NSs were replaced by arginine residues, expresses an NSs protein (NSs4KR) that is resistant to degradation, confirming that degradation is lysine-dependent. However, despite repeated attempts, no direct ubiquitylation of NSs in infected cells could be demonstrated. This suggests that degradation of NSs, although lysine-dependent, may be achieved through an indirect mechanism. Infection of cultured mammalian cells or mice indicated no disadvantage for the virus in having a non-degradable NSs protein: in fact rBUN4KR had a slight growth advantage over wtBUNV in interferon-competent cells, presumably due to the increased and prolonged presence of NSs. In cultured mosquito cells there was no difference in growth between wild-type BUNV and rBUN4KR, but surprisingly NSs4KR was not stabilised compared to the wild-type NSs protein.

  18. Resveratrol prevents age-related memory and mood dysfunction with increased hippocampal neurogenesis and microvasculature, and reduced glial activation.

    Science.gov (United States)

    Kodali, Maheedhar; Parihar, Vipan K; Hattiangady, Bharathi; Mishra, Vikas; Shuai, Bing; Shetty, Ashok K

    2015-01-28

    Greatly waned neurogenesis, diminished microvasculature, astrocyte hypertrophy and activated microglia are among the most conspicuous structural changes in the aged hippocampus. Because these alterations can contribute to age-related memory and mood impairments, strategies efficacious for mitigating these changes may preserve cognitive and mood function in old age. Resveratrol, a phytoalexin found in the skin of red grapes having angiogenic and antiinflammatory properties, appears ideal for easing these age-related changes. Hence, we examined the efficacy of resveratrol for counteracting age-related memory and mood impairments and the associated detrimental changes in the hippocampus. Two groups of male F344 rats in late middle-age having similar learning and memory abilities were chosen and treated with resveratrol or vehicle for four weeks. Analyses at ~25 months of age uncovered improved learning, memory and mood function in resveratrol-treated animals but impairments in vehicle-treated animals. Resveratrol-treated animals also displayed increased net neurogenesis and microvasculature, and diminished astrocyte hypertrophy and microglial activation in the hippocampus. These results provide novel evidence that resveratrol treatment in late middle age is efficacious for improving memory and mood function in old age. Modulation of the hippocampus plasticity and suppression of chronic low-level inflammation appear to underlie the functional benefits mediated by resveratrol.

  19. Zinc can increase the activity of protein kinase C and contributes to its binding to plasma membranes in T lymphocytes.

    Science.gov (United States)

    Csermely, P; Szamel, M; Resch, K; Somogyi, J

    1988-05-15

    In the primary structure of protein kinase C, the presence of a putative metal-binding site has been suggested (Parker, P.J., Coussens, L., Totty, N., Rhee, L., Young, S., Chen, E., Stabel, S., Waterfield, M.D., and Ullrich, A. (1986) Science 233, 853-859). In the present report, we demonstrate that the most abundant intracellular heavy metal, zinc, can increase the activity of cytosolic protein kinase C. Zinc reversibly binds the enzyme to plasma membranes, and it may contribute to the calcium-induced binding as well. The intracellular heavy metal chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine prevents the phorbol ester- and antigen-induced translocation of protein kinase C. This effect can be totally reversed by the concomitant addition of Zn2+, while Fe2+ and Mn2+ are only partially counteractive. Our results suggest that zinc can activate protein kinase C and contributes to its binding to plasma membranes in T lymphocytes induced by Ca2+, phorbol ester, or antigen.

  20. Triglyceride concentration and waist circumference influence alcohol-related plasminogen activator inhibitor-1 activity increase in black South Africans.

    Science.gov (United States)

    Pieters, Marlien; de Lange, Zelda; Hoekstra, Tiny; Ellis, Suria M; Kruger, Annamarie

    2010-12-01

    We investigated the association between alcohol consumption and plasminogen activator inhibitor-1 activity (PAI-1act) and fibrinogen concentration in a black South African population presenting with lower PAI-1act and higher fibrinogen than what is typically observed in white populations. We, furthermore, wanted to investigate the effect of urbanization, sex, central obesity, increased triglycerides, 4G/5G polymorphism (PAI-1 only) and BMI on the association of alcohol with PAI-1act and fibrinogen. Data from 2010 apparently healthy, randomly collected black South African volunteers from the Prospective Urban and Rural Epidemiological (PURE) study were cross-sectionally analyzed. Alcohol consumption was recorded using quantitative food frequency questionnaires and fasting blood samples were collected for biochemical analysis including PAI-1act and fibrinogen. Heavy alcohol consumption is associated with significantly increased PAI-1act, in the total population as well as in the women separately, and tended to be so in men. This alcohol-related PAI-1act increase was observed in volunteers with increased triglycerides and central obesity but not in volunteers with normal levels and waist circumference. Urbanization, the 4G/5G polymorphism and BMI did not affect the association of alcohol with PAI-1act. Moderate alcohol consumption is associated with decreased fibrinogen concentration. Sex and level of urbanization did not affect the association of alcohol with fibrinogen. Fibrinogen decreased in normal and overweight volunteers but not in obese and centrally obese volunteers following moderate alcohol consumption. Triglyceride levels and waist circumference influence alcohol-related PAI-1act increase potentially through modulating adipocyte and triglyceride-induced PAI-1 production. Obesity prevented alcohol-related fibrinogen decrease possibly by counteracting the anti-inflammatory effect of moderate alcohol consumption.

  1. CB1 receptor antagonism increases hippocampal acetylcholine release: site and mechanism of action.

    Science.gov (United States)

    Degroot, Aldemar; Köfalvi, Attila; Wade, Mark R; Davis, Richard J; Rodrigues, Ricardo J; Rebola, Nelson; Cunha, Rodrigo A; Nomikos, George G

    2006-10-01

    Evidence indicates that blockade of cannabinoid receptors increases acetylcholine (ACh) release in brain cortical regions. Although it is assumed that this type of effect is mediated through CB1 receptor (CB1R) antagonism, several in vitro functional studies recently have suggested non-CB1R involvement. In addition, neither the precise neuroanatomical site nor the exact mechanisms underlying this effect are known. We thoroughly examined these issues using a combination of systemic and local administration of CB1R antagonists, different methods of in vivo microdialysis, CB1R knockout (KO) mice, tissue measurements of ACh, and immunochemistry. First, we showed that systemic injections of the CB1R antagonists N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR-141716A) and N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) dose-dependently increased hippocampal ACh efflux. Likewise, local hippocampal, but not septal, infusions of SR141716A or AM251 increased hippocampal ACh release. It is noteworthy that the stimulatory effects of systemically administered CB1R antagonists on hippocampal ACh release were completely abolished in CB1R KO mice. CB1R KO mice had similar basal but higher stress-enhanced hippocampal ACh levels compared with wild-type controls. It is interesting that dopamine D1 receptor antagonism counteracted the stimulatory effect of CB1R blockade on hippocampal ACh levels. Finally, immunohistochemical methods revealed that a high proportion of CB1R-positive nerve terminals were found in hippocampus and confirmed the colocalization of CB1 receptors with cholinergic and dopaminergic nerve terminals. In conclusion, hippocampal ACh release may specifically be controlled through CB1Rs located on both cholinergic and dopaminergic neuronal projections, and CB1R antagonism increases hippocampal ACh release, probably through both a direct

  2. Planning for Increased Bioenergy use - Strategies for Minimising Environmental Impacts and Analysing the Consequences

    International Nuclear Information System (INIS)

    Jonsson, Anna

    2006-08-01

    There are several goals aimed at increasing the use of renewable energy in the Swedish energy system. Bioenergy is one important renewable energy source and there is a potential to increase its use in the future. This thesis aimed to develop and analyse strategies and tools that could be used when planning for conversion to bioenergy-based heating systems and the building of new residential areas with bioenergy-based heating. The goal was to enable the increase of bioenergy and simultaneously minimise the negative health effects caused by emissions associated with the combustion of bioenergy. The thesis consists of two papers. Paper I concerned existing residential areas and conversion from electric heating and individual heating systems, such as firewood and oil boilers, to more modern and low-emitting pellet techniques and small-scale district heating. Paper II concerned new residential areas and how to integrate bioenergy-based heating systems that cause impacts on local air quality into the physical planning process through using Geographical Information Systems (GIS) and a meteorological dispersion model, ALARM. The results from Paper I indicated that it was possible to convert areas currently using electric heating to pellet techniques and small-scale district heating without degrading local air quality. Furthermore, it was possible to decrease high emissions caused by firewood boilers by replacing them with pellet boilers. The results from Paper II highlighted that GIS and ALARM were advantageous for analysing local air quality characteristics when planning for new residential areas and before a residential area is built: thus, avoiding negative impacts caused by bioenergy-based combustion. In conclusion, the work procedures developed in this thesis can be used to counteract negative impacts on local air quality with increasing use of bioenergy in the heating system. Analysis of potentially negative aspects before conversion to bioenergy-based heating

  3. Lipid nanoparticles to counteract gastric infection without affecting gut microbiota.

    Science.gov (United States)

    Seabra, Catarina Leal; Nunes, Cláudia; Brás, Manuela; Gomez-Lazaro, Maria; Reis, Celso A; Gonçalves, Inês C; Reis, Salette; Martins, M Cristina L

    2018-06-01

    Helicobacter pylori infection is one of the major risk factors for gastric cancer development. Available antibiotic-based treatments not only fail in around 20% of patients but also have a severe negative impact on the gut microbiota. Recently, we demonstrated that nanostructured lipid carriers (NLC), even without any drug loaded, are bactericidal against H. pylori at low concentrations. This work aims to clarify NLC mode of action and to evaluate if their bactericidal effect is specific to H. pylori without affecting bacteria from microbiota. NLC were produced by hot homogenization followed by ultrasonication method, using Precirol®ATO5 and Miglyol®812 as lipids and Tween®60 as a surfactant. NLC were able to eradicate H. pylori without affecting the other tested bacteria (Lactobacillus, E. coli, S. epidermidis and S. aureus). Bioimaging assays demonstrated that NLC rapidly bind to and cross the H. pylori bacterial membrane, destabilizing and disrupting it, which leads to leakage of the cytoplasmic contents and consequent bacterial death. In an era where efficient alternatives to antibiotics are urgent, NLC are an interesting route to be explored in the quest for new antibiotic-free therapies to fight H. pylori infection. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Pathogen self defense: mechanisms to counteract microbial antagonism

    NARCIS (Netherlands)

    Duffy, B.K.; Schouten, A.; Raaijmakers, J.M.

    2003-01-01

    Natural and agricultural ecosystems harbor a wide variety of microorganisms that play an integral role in plant health, crop productivity, and preservation of multiple ecosystem functions. Interactions within and among microbial communities are numerous and range from synergistic and mutualistic to

  5. Can budget institutions counteract political indiscipline? / Stefania Fabrizio, Ashoka Mody

    Index Scriptorium Estoniae

    Fabrizio, Stefania

    2006-01-01

    Artiklis analüüsitakse finantsinstitutsioonide ning valitsuse poliitika mõju riigi eelarvepoliitikale ja finantskäitumisele EL uute liikmesriikide näitel aastatel 1997-2003. Tabelid, diagrammid, lisad. Artikli autoritega diskuteerivad Giancarlo Corsetti, Jonathan R.W. Temple

  6. [Measures for counteracting of biological terrorism in the Russian Federation].

    Science.gov (United States)

    Onishchenko, G G

    2005-01-01

    The article deals with topicality of the problem of ensuring biological safety in Russia. The necessity of a unified state policy aimed at the realization of the concept of biological safety is grounded. In particular, the expediency of the state support of research programs is emphasized. The organizational and practical measures, carried out by the Ministry of Health and Social Development in this field, are analyzed. The list of prospective measures for the organization of effective state regulation in the field of ensuring the biological safety of the country is given.

  7. Sialyltransferase activity probably counteracts that of sialidase as ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-12-29

    Dec 29, 2008 ... protection to and adaptation to life, but they have been found to be utilized ... The anti-recognition effect of SAs is exerted by their negative charge .... red cell precursors in the bone marrow (Wikipedia, 2006). The concept that ..... nutrition on milk production and some biochemical parameters in. West African ...

  8. Electrical stimulation counteracts muscle atrophy associated with aging in humans

    Directory of Open Access Journals (Sweden)

    Helmut Kern

    2013-07-01

    Full Text Available Functional and structural muscle decline is a major problem during aging. Our goal was to improve in old subjects quadriceps m. force and mobility functional performances (stair test, chair rise test, timed up and go test with neuromuscular electrical stimulation (9 weeks, 2-3times/week, 20-30 minutes per session. Furthermore we performed histological and biological molecular analyses of vastus lateralis m. biopsies. Our findings demonstrate that electrical stimulation significantly improved mobility functional performancies and muscle histological characteristics and molecular markers.

  9. An Icing Of Aircraft – Reasons, Consequences, Counteraction

    Directory of Open Access Journals (Sweden)

    Gębura Andrzej

    2014-12-01

    Full Text Available The article presents reasons of an helicopter’s ising as well as an aircraft’s ising. The maion attention is addressed a conteraction of an ising. Autors divide the problem an two groups: an ising of an airframe – mostly lifting surfaces, an ising of engines. According to authors reasons, an extension (first of all consequences of airframe’s ising considerably differ from seemingly similar events in an engine. The considerable attention is concentrated on a connteraction of consequences of an ising during the flight. The most complicated ising referes to helicopters, considering their particular aerodynamics characteristics. The autors dedicated is greather attention. Results reached during investigations of heating rotor blades in ITWL are presented.

  10. Counteraction to the Hidden Channels of Delivery of Malwares

    Directory of Open Access Journals (Sweden)

    Dmitriy Gennadievich Khomutov

    2013-06-01

    Full Text Available Article is devoted to the description of actual ways of possible distribution of malwares such, as “Easter eggs”, client network applications (torrent-client and service of digital distribution. As the experiment description on distribution of malwares is provided in the simulated virtual network by means of service of digital distribution. Rules on safety of the user computers in a network are developed.

  11. MDM2 Antagonists Counteract Drug-Induced DNA Damage

    Directory of Open Access Journals (Sweden)

    Anna E. Vilgelm

    2017-10-01

    Full Text Available Antagonists of MDM2-p53 interaction are emerging anti-cancer drugs utilized in clinical trials for malignancies that rarely mutate p53, including melanoma. We discovered that MDM2-p53 antagonists protect DNA from drug-induced damage in melanoma cells and patient-derived xenografts. Among the tested DNA damaging drugs were various inhibitors of Aurora and Polo-like mitotic kinases, as well as traditional chemotherapy. Mitotic kinase inhibition causes mitotic slippage, DNA re-replication, and polyploidy. Here we show that re-replication of the polyploid genome generates replicative stress which leads to DNA damage. MDM2-p53 antagonists relieve replicative stress via the p53-dependent activation of p21 which inhibits DNA replication. Loss of p21 promoted drug-induced DNA damage in melanoma cells and enhanced anti-tumor activity of therapy combining MDM2 antagonist with mitotic kinase inhibitor in mice. In summary, MDM2 antagonists may reduce DNA damaging effects of anti-cancer drugs if they are administered together, while targeting p21 can improve the efficacy of such combinations.

  12. Targeting Mitochondria to Counteract Age-Related Cellular Dysfunction

    Directory of Open Access Journals (Sweden)

    Corina T. Madreiter-Sokolowski

    2018-03-01

    Full Text Available Senescence is related to the loss of cellular homeostasis and functions, which leads to a progressive decline in physiological ability and to aging-associated diseases. Since mitochondria are essential to energy supply, cell differentiation, cell cycle control, intracellular signaling and Ca2+ sequestration, fine-tuning mitochondrial activity appropriately, is a tightrope walk during aging. For instance, the mitochondrial oxidative phosphorylation (OXPHOS ensures a supply of adenosine triphosphate (ATP, but is also the main source of potentially harmful levels of reactive oxygen species (ROS. Moreover, mitochondrial function is strongly linked to mitochondrial Ca2+ homeostasis and mitochondrial shape, which undergo various alterations during aging. Since mitochondria play such a critical role in an organism’s process of aging, they also offer promising targets for manipulation of senescent cellular functions. Accordingly, interventions delaying the onset of age-associated disorders involve the manipulation of mitochondrial function, including caloric restriction (CR or exercise, as well as drugs, such as metformin, aspirin, and polyphenols. In this review, we discuss mitochondria’s role in and impact on cellular aging and their potential to serve as a target for therapeutic interventions against age-related cellular dysfunction.

  13. A HUMAN RIGHTS-BASED APPROACH TO COUNTERACT ...

    African Journals Online (AJOL)

    milkii

    54Elizabeth Yuko, 'Theories, Practices and Promises: Human Trafficking Laws and Policies in. Destination States of ..... Further, the verification of nationality is a bit challenging since several trafficked ... Djibouti as a site for a self-help project.

  14. Why Does Gender Matter? Counteracting Stereotypes with Young Children

    Science.gov (United States)

    Aina, Olaiya E.; Cameron, Petronella A.

    2011-01-01

    The early gender bias experiences that children encounter can shape their attitudes and beliefs related to their development of interpersonal and intrapersonal relationships, access to education equality, participation in the corporate work world, as well as stifling their physical and psychological well being. For early childhood educators, being…

  15. Plant-Derived Agents for Counteracting Cisplatin-Induced Nephrotoxicity

    OpenAIRE

    Ojha, Shreesh; Venkataraman, Balaji; Kurdi, Amani; Mahgoub, Eglal; Sadek, Bassem; Rajesh, Mohanraj

    2016-01-01

    Cisplatin (CSP) is a chemotherapeutic agent commonly used to treat a variety of malignancies. The major setback with CSP treatment is that its clinical efficacy is compromised by its induction of organ toxicity, particular to the kidneys and ears. Despite the significant strides that have been made in understanding the mechanisms underlying CSP-induced renal toxicity, advances in developing renoprotective strategies are still lacking. In addition, the renoprotective approaches described in th...

  16. Chitosan application in maize ( Zea mays ) to counteract the effects ...

    African Journals Online (AJOL)

    There are several strategies for managing the problem, but in the future, people will prefer the cleaner and cheaper technology. The use of elicitors for protection of corn can be considered a cheap and clean technology. Chitosan elicitor is a linear polysaccharide produced commercially by deacetylation of chitin. It has been ...

  17. FDTD Modeling and Counteraction to Scintillation Effects in the lonosphere

    Science.gov (United States)

    2014-04-05

    collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT...for vectorial diffraction calculations and its numerical implementation,” J. Opt. Soc. Am. A, 23 (3), pp. 713-722, 2006. [21] Coe, R. L. and E. J...Seibel, “Improved near-field calculations using vectorial diffraction integrals in the finite-difference time-domain method,” J. Opt. Soc. Am. A, 28

  18. Listening to white noise counteracts visual and haptic pseudoneglect.

    Science.gov (United States)

    Cattaneo, Zaira; Lega, Carlotta; Vecchi, Tomaso; Vallar, Giuseppe

    2012-01-01

    Neurologically intact individuals usually show a leftward bias in line bisection, a tendency known as "pseudoneglect", likely reflecting a right-hemisphere dominance in controlling the allocation of spatial attention. Studies in brain-damaged patients with left visuospatial neglect have reported that auditory stimulation may reduce the deficit, both in a spatially dependent and in a spatially independent way. Here we show for the first time that the concurrent binaural presentation of auditory white noise affects healthy individuals' performance in both visual and haptic bisection, reducing their leftward error. We suggest that this effect depends on the noise boosting alertness and restoring the hemispheric activation balance. Our data clearly show that task-irrelevant auditory noise crossmodally affects the allocation of spatial resources in both the haptic and the visual space; future research may clarify whether these effects are specific for the type of auditory stimulation.

  19. Alteration of host-pathogen interactions in the wake of climate change - Increasing risk for shellfish associated infections?

    Science.gov (United States)

    Hernroth, Bodil E; Baden, Susanne P

    2018-02-01

    The potential for climate-related spread of infectious diseases through marine systems has been highlighted in several reports. With this review we want to draw attention to less recognized mechanisms behind vector-borne transmission pathways to humans. We have focused on how the immune systems of edible marine shellfish, the blue mussels and Norway lobsters, are affected by climate related environmental stressors. Future ocean acidification (OA) and warming due to climate change constitute a gradually increasing persistent stress with negative trade-off for many organisms. In addition, the stress of recurrent hypoxia, inducing high levels of bioavailable manganese (Mn) is likely to increase in line with climate change. We summarized that OA, hypoxia and elevated levels of Mn did have an overall negative effect on immunity, in some cases also with synergistic effects. On the other hand, moderate increase in temperature seems to have a stimulating effect on antimicrobial activity and may in a future warming scenario counteract the negative effects. However, rising sea surface temperature and climate events causing high land run-off promote the abundance of naturally occurring pathogenic Vibrio and will in addition, bring enteric pathogens which are circulating in society into coastal waters. Moreover, the observed impairments of the immune defense enhance the persistence and occurrence of pathogens in shellfish. This may increase the risk for direct transmission of pathogens to consumers. It is thus essential that in the wake of climate change, sanitary control of coastal waters and seafood must recognize and adapt to the expected alteration of host-pathogen interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Selective estrogen receptor modulator promotes weight loss in ovariectomized female rhesus monkeys (Macaca mulatta) by decreasing food intake and increasing activity.

    Science.gov (United States)

    Sullivan, Elinor L; Shearin, Jean; Koegler, Frank H; Cameron, Judy L

    2012-04-01

    The effect of hormone replacement therapy (HRT) on body weight in postmenopausal women is controversial, with studies reporting an increase, a decrease, and no change in body weight. To examine estrogen receptor actions on body weight, we investigated the effects of treatment with a selective estrogen receptor modulator (SERM) on body weight, food intake, and activity and metabolic rate in a nonhuman primate model. Eighteen ovariectomized female rhesus monkeys were treated with a nonsteroidal SERM (GSK232802A, 5 mg/kg po) for 3 mo. GSK232802A decreased lutenizing hormone (P Physical activity increased during the 3rd mo of treatment (P = 0.04). Baseline activity level and the change in activity due to treatment were correlated, with the most sedentary individuals exhibiting increased physical activity during the 1st mo of treatment (P = 0.02). Metabolic rate did not change (P = 0.58). These results indicate that GSK232802A treatment reduces body weight and adiposity in ovariectomized nonhuman primates by suppressing food intake and increasing activity, particularly in the most sedentary individuals. These findings suggest that SERM treatment may counteract weight gain in postmenopausal women.

  1. Experimentally increased nutrient availability at the permafrost thaw front selectively enhances biomass production of deep-rooting subarctic peatland species.

    Science.gov (United States)

    Keuper, Frida; Dorrepaal, Ellen; van Bodegom, Peter M; van Logtestijn, Richard; Venhuizen, Gemma; van Hal, Jurgen; Aerts, Rien

    2017-10-01

    biomass production beyond the already established impact of warming-driven enhanced shallow N-mineralization. This may result in shifts in plant community composition and may partially counteract the increased carbon losses from thawing permafrost. © 2017 John Wiley & Sons Ltd.

  2. Inhaled Beta2-agonist increases power output and glycolysis during sprinting in men

    DEFF Research Database (Denmark)

    Kalsen, Anders; Hostrup, Morten; Söderlund, Karin

    2016-01-01

    . Moreover, net rate of glycogenolysis (6.5±0.8 vs. 3.1±0.7 mmol glucosyl units kg dw s) and glycolysis (2.4±0.2 vs. 1.6±0.2 mmol glucosyl units kg dw s) were higher (P... and glycolysis in skeletal muscles. Furthermore, as terbutaline counteracted a reduction in ATP in type II fibers, terbutaline may postpone fatigue development in these fibers....

  3. Physical exercise in aging human skeletal muscle increases mitochondrial calcium uniporter expression levels and affects mitochondria dynamics.

    Science.gov (United States)

    Zampieri, Sandra; Mammucari, Cristina; Romanello, Vanina; Barberi, Laura; Pietrangelo, Laura; Fusella, Aurora; Mosole, Simone; Gherardi, Gaia; Höfer, Christian; Löfler, Stefan; Sarabon, Nejc; Cvecka, Jan; Krenn, Matthias; Carraro, Ugo; Kern, Helmut; Protasi, Feliciano; Musarò, Antonio; Sandri, Marco; Rizzuto, Rosario

    2016-12-01

    Age-related sarcopenia is characterized by a progressive loss of muscle mass with decline in specific force, having dramatic consequences on mobility and quality of life in seniors. The etiology of sarcopenia is multifactorial and underlying mechanisms are currently not fully elucidated. Physical exercise is known to have beneficial effects on muscle trophism and force production. Alterations of mitochondrial Ca 2+ homeostasis regulated by mitochondrial calcium uniporter (MCU) have been recently shown to affect muscle trophism in vivo in mice. To understand the relevance of MCU-dependent mitochondrial Ca 2+ uptake in aging and to investigate the effect of physical exercise on MCU expression and mitochondria dynamics, we analyzed skeletal muscle biopsies from 70-year-old subjects 9 weeks trained with either neuromuscular electrical stimulation (ES) or leg press. Here, we demonstrate that improved muscle function and structure induced by both trainings are linked to increased protein levels of MCU Ultrastructural analyses by electron microscopy showed remodeling of mitochondrial apparatus in ES-trained muscles that is consistent with an adaptation to physical exercise, a response likely mediated by an increased expression of mitochondrial fusion protein OPA1. Altogether these results indicate that the ES-dependent physiological effects on skeletal muscle size and force are associated with changes in mitochondrial-related proteins involved in Ca 2+ homeostasis and mitochondrial shape. These original findings in aging human skeletal muscle confirm the data obtained in mice and propose MCU and mitochondria-related proteins as potential pharmacological targets to counteract age-related muscle loss. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  4. Polysaccharide from Fuzi protects against Ox-LDL-induced calcification of human vascular smooth muscle cells by increasing autophagic activity

    Science.gov (United States)

    Liao, Lizhen; Zhuang, Xiaodong; Li, Weidong; Su, Qibiao; Zhao, Jie; Liu, Ying

    2018-01-01

    Polysaccharide from Fuzi (FPS) is a water-soluble polysaccharide isolated from the traditional Chinese herbal medicine Fuzi. It has been demonstrated to protect hepatocytes against ischemia-reperfusion injury through its potent antioxidant effects, and to attenuate starvation-induced cytotoxicity in H9c2 cells by increasing autophagic activity. In the present study, Alizarin Red S staining was used to detect mineral deposition and reverse transcription-quantitative polymerase chain reaction was used to detect the core binding factor α1 and smooth muscle 22α mRNA expression. To analyze autophagic activity, western blotting was used to detect microtubule-associated protein 1A/1B light chain 3 and nucleoporin P62 expression. In addition, green fluorescent protein-LC3 dots-per-cell was observed by fluorescence microscopy. It was demonstrated that oxidized low-density lipoprotein (Ox-LDL) could increase the calcification of human vascular smooth muscle cells (VSMCs) in a concentration-dependent manner, and that FPS treatment had a significant protective effect against Ox-LDL-induced calcification of human VSMCs. Furthermore, FPS treatment alleviated the Ox-LDL-induced downregulation of autophagic activity, and the protective effect of FPS on Ox-LDL-induced calcification was attenuated by the autophagy inhibitor 3-methyladenine. In conclusion, the present study demonstrated for the first time to the best of the authors' knowledge that FPS can protect against Ox-LDL-induced vascular calcification in human VSMCs, and that this likely occurs via the activation of autophagy. This supports the hypothesis that autophagy may be an endogenous protective mechanism counteracting vascular calcification, and that FPS may be used as a potential therapeutic for vascular calcification. PMID:29393437

  5. Large and abundant flowers increase indirect costs of corollas: a study of coflowering sympatric Mediterranean species of contrasting flower size.

    Science.gov (United States)

    Teixido, Alberto L; Valladares, Fernando

    2013-09-01

    Large floral displays receive more pollinator visits but involve higher production and maintenance costs. This can result in indirect costs which may negatively affect functions like reproductive output. In this study, we explored the relationship between floral display and indirect costs in two pairs of coflowering sympatric Mediterranean Cistus of contrasting flower size. We hypothesized that: (1) corolla production entails direct costs in dry mass, N and P, (2) corollas entail significant indirect costs in terms of fruit set and seed production, (3) indirect costs increase with floral display, (4) indirect costs are greater in larger-flowered sympatric species, and (5) local climatic conditions influence indirect costs. We compared fruit set and seed production of petal-removed flowers and unmanipulated control flowers and evaluated the influence of mean flower number and mean flower size on relative fruit and seed gain of petal-removed and control flowers. Fruit set and seed production were significantly higher in petal-removed flowers in all the studied species. A positive relationship was found between relative fruit gain and mean individual flower size within species. In one pair of species, fruit gain was higher in the large-flowered species, as was the correlation between fruit gain and mean number of open flowers. In the other pair, the correlation between fruit gain and mean flower size was also higher in the large-flowered species. These results reveal that Mediterranean environments impose significant constraints on floral display, counteracting advantages of large flowers from the pollination point of view with increased indirect costs of such flowers.

  6. Worldwide Increasing Incidences of Cutaneous Malignant Melanoma

    International Nuclear Information System (INIS)

    Godar, D. E.

    2011-01-01

    The incidence of cutaneous malignant melanoma (CMM) has been increasing at a steady rate in fair-skinned populations around the world for decades. Scientists are not certain why CMM has been steadily increasing, but strong, intermittent UVB (290-320 nm) exposures, especially sunburn episodes, probably initiate, CMM, while UVA (321-400 nm) passing through glass windows in offices and cars probably promotes it. The CMM incidence may be increasing at an exponential rate around the world, but it definitely decreases with increasing latitude up to∼ 50 degree N where it reverses and increases with the increasing latitude. The inversion in the incidence of CMM may occur because there is more UVA relative to UVB for most of the year at higher latitudes. If windows, allowing UVA to enter our indoor-working environment and cars, are at least partly responsible for the increasing incidence of CMM, then UV filters can be applied to reduce the rate of increase worldwide.

  7. 3 Ways to Increase Positive Emotions

    Science.gov (United States)

    ... Search English Español 3 Ways to Increase Positive Emotions KidsHealth / For Teens / 3 Ways to Increase Positive ... to give yourself a boost. Track Your Positive Emotions Name the positive emotions you're already familiar ...

  8. Increasing millet production in South Asia

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

    Asia, which has put the emphasis on cash crops and cereals ... aims to increase production and consumption of minor ... practices. They will then develop sustainable agriculture tool kits to help farmers to increase millet production in these.

  9. Advanced Glycation Endproducts Are Increased in the Animal Model of Multiple Sclerosis but Cannot Be Reduced by Pyridoxamine Treatment or Glyoxalase 1 Overexpression

    Directory of Open Access Journals (Sweden)

    Suzan Wetzels

    2018-04-01

    Full Text Available Multiple sclerosis (MS is a demyelinating autoimmune disease of the central nervous system (CNS. The immune response in MS patients leads to the infiltration of immune cells in the CNS and their subsequent activation. Immune cell activation induces a switch towards glycolysis. During glycolysis, the dicarbonyl product methylglyoxal (MGO is produced. MGO is a glycating agent that can rapidly form advanced glycation endproducts (AGEs. In turn, AGEs are able to induce inflammatory responses. The glyoxalase system is the endogenous defense system of the body to reduce the burden of MGO thereby reducing AGE formation. This system consists of glyoxalase-1 and glyoxalase-2 which are able to detoxify MGO to D-lactate. We investigated whether AGE levels are induced in experimental autoimmune encephalitis (EAE, an inflammatory animal model of MS. Twenty seven days post EAE induction, MGO and AGE (Nε-(carboxymethyllysine (CML, Nε-(carboxyethyllysine (CEL, 5-hydro-5-methylimidazolone (MG-H1 levels were significantly increased in the spinal cord of mice subjected to EAE. Yet, pyridoxamine treatment and glyoxalase-1 overexpression were unable to counteract AGE production during EAE and did not influence the clinical course of EAE. In conclusion, AGEs levels increase during EAE in the spinal cord, but AGE-modifying treatments do not inhibit EAE-induced AGE production and do not affect disease progression.

  10. The prevalence of the metabolic syndrome did not increase in Mexico City between 1990-1992 and 1997-1999 despite more central obesity.

    Science.gov (United States)

    Lorenzo, Carlos; Williams, Ken; Gonzalez-Villalpando, Clicerio; Haffner, Steven M

    2005-10-01

    Trends in the metabolic syndrome might follow trends in obesity. We examined this hypothesis in the Mexico City Diabetes Study (MCDS), a study that showed rising trends in obesity, and the effect of the metabolic syndrome on the risk of coronary heart disease (CHD). Designed as a population-based study, the MCDS enrolled subjects in 1990-1992 (n = 2,282). Follow-up visits were held in 1993-1995 (n = 1,764) and 1997-1999 (n = 1,754). We used the revised metabolic syndrome definition of the National Cholesterol Education Program and the Framingham equations to estimate the 10-year CHD risk. In men, the age-adjusted prevalence of the metabolic syndrome was 38.9% in 1990-1992, 43.4% in 1993-1995, and 39.9% in 1997-1999; in women, the prevalences were 65.4, 65.7, and 59.9%, respectively. The prevalence did not change in men (P = 0.349) between 1990-1992 and 1997-1999, but decreased in women (P metabolic syndrome nor CHD risk has increased in Mexico City. Lower blood pressure and triglyceride values appear to have counteracted increases in central obesity and fasting glucose.

  11. The cytoplasmic C-terminus of polycystin-1 increases cell proliferation in kidney epithelial cells through serum-activated and Ca2+-dependent pathway(s)

    International Nuclear Information System (INIS)

    Manzati, Elisa; Aguiari, Gianluca; Banzi, Manuela; Manzati, Michele; Selvatici, Rita; Falzarano, Sofia; Maestri, Iva; Pinton, Paolo; Rizzuto, Rosario; Senno, Laura del

    2005-01-01

    Polycystin-1 (PC1) is a large transmembrane protein important in renal differentiation and defective in most cases of autosomal dominant polycystic kidney disease (ADPKD), a common cause of renal failure in adults. Although the genetic basis of ADPKD has been elucidated, molecular and cellular mechanisms responsible for the dysregulation of epithelial cell growth in ADPKD cysts are still not well defined. We approached this issue by investigating the role of the carboxyl cytoplasmic domain of PC1 involved in signal transduction on the control of kidney cell proliferation. Therefore, we generated human HEK293 cells stably expressing the PC1 cytoplasmic tail as a membrane targeted TrkA-PC1 chimeric receptor protein (TrkPC1). We found that TrkPC1 increased cell proliferation through an increase in cytoplasmic Ca 2+ levels and activation of PKCα, thereby upregulating D1 and D3 cyclin, downregulating p21 waf1 and p27 kip1 cyclin inhibitors, and thus inducing cell cycle progression from G0/G1 to the S phase. Interestingly, TrkPC1-dependent Ca 2+ increase and PKCα activation are not constitutive, but require serum factor(s) as parallel component. In agreement with this observation, a significant increase in ERK1/2 phosphorylation was observed. Consistently, inhibitors specifically blocking either PKCα or ERK1/2 prevented the TrkPC1-dependent proliferation increase. NGF, the TrkA ligand, blocked this increase. We propose that in kidney epithelial cells the overexpression of PC1 C-terminus upregulates serum-evoked intracellular Ca 2+ by counteracting the growth-suppression activity of endogenous PC1 and leading to an increase in cell proliferation

  12. Announcing the arrival of enrichment increases play behaviour and reduces weaning-stress-induced behaviours of piglets directly after weaning

    NARCIS (Netherlands)

    Dudink, S.; Simonse, H.; Marks, I.; Jonge, de F.H.; Spruijt, B.M.

    2006-01-01

    Piglets have difficulties with the abrupt changes at weaning associated with conventional pig production systems. Previously, it has been shown in rats that reward and announcement of reward counteracts impact of stress effects. In the present study, it was investigated if announcement of an

  13. Non-B DNA-forming sequences and WRN deficiency independently increase the frequency of base substitution in human cells

    DEFF Research Database (Denmark)

    Bacolla, Albino; Wang, Guliang; Jain, Aklank

    2011-01-01

    Although alternative DNA secondary structures (non-B DNA) can induce genomic rearrangements, their associated mutational spectra remain largely unknown. The helicase activity of WRN, which is absent in the human progeroid Werner syndrome, is thought to counteract this genomic instability. We dete...

  14. Taurine increases hippocampal neurogenesis in aging mice

    Directory of Open Access Journals (Sweden)

    Elias Gebara

    2015-05-01

    Full Text Available Aging is associated with increased inflammation and reduced hippocampal neurogenesis, which may in turn contribute to cognitive impairment. Taurine is a free amino acid found in numerous diets, with anti-inflammatory properties. Although abundant in the young brain, the decrease in taurine concentration with age may underlie reduced neurogenesis. Here, we assessed the effect of taurine on hippocampal neurogenesis in middle-aged mice. We found that taurine increased cell proliferation in the dentate gyrus through the activation of quiescent stem cells, resulting in increased number of stem cells and intermediate neural progenitors. Taurine had a direct effect on stem/progenitor cells proliferation, as observed in vitro, and also reduced activated microglia. Furthermore, taurine increased the survival of newborn neurons, resulting in a net increase in adult neurogenesis. Together, these results show that taurine increases several steps of adult neurogenesis and support a beneficial role of taurine on hippocampal neurogenesis in the context of brain aging.

  15. Increased muscle glucose uptake during contractions

    DEFF Research Database (Denmark)

    Ploug, Thorkil; Galbo, Henrik; Richter, Erik

    1984-01-01

    We reinvestigated the prevailing concept that muscle contractions only elicit increased muscle glucose uptake in the presence of a so-called "permissive" concentration of insulin (Berger et al., Biochem. J. 146: 231-238, 1975; Vranic and Berger, Diabetes 28: 147-163, 1979). Hindquarters from rats...... in severe ketoacidosis were perfused with a perfusate containing insulin antiserum. After 60 min perfusion, electrical stimulation increased glucose uptake of the contracting muscles fivefold. Also, subsequent contractions increased glucose uptake in hindquarters from nondiabetic rats perfused for 1.5 h......-methylglucose uptake increased during contractions and glucose uptake was negative at rest and zero during contractions. An increase in muscle transport and uptake of glucose during contractions does not require the presence of insulin. Furthermore, glucose transport in contracting muscle may only increase if glycogen...

  16. Increase of internal energy due to measurement

    International Nuclear Information System (INIS)

    Daboul, J.

    1991-01-01

    We argue that the internal energy E=(H) of a macroscopic system in thermal equilibrium must increase, if we measure an observable A which does not commute with the Hamiltonian H. We derive an expression for calculating a lower bound for this increase in E. We then generalize the above result, and show that under certain conditions the expectation value (C) of an observable C should increase by the measurement of another observable A, if A and C do not commute. (author)

  17. Charcot's osteoarthropathy: An increased awareness of this ...

    African Journals Online (AJOL)

    Charcot's osteoarthropathy: An increased awareness of this condition may help in enabling an earlier diagnosis, instituting appropriate treatment, and preventing severe deformity and disability. T Johnson ...

  18. The increased importance of sector switching

    DEFF Research Database (Denmark)

    Frederiksen, Anders; Hansen, Jesper Rosenberg

    2017-01-01

    Sector switching is an important phenomenon that casts light on public–private differences. Yet our knowledge about its prevalence and trends is limited. We study sector switching using unique Danish register-based employer–employee data covering more than 25 years. We find that sector switching...... constitutes 18.5% of all job-to-job mobility, and the trend is increasing both from public to private and from private to public. Sector switching is also generally increasing for middle managers, but for administrative professionals only the flows from private to public increase and for top managers only...... the flows from public to private increase....

  19. Medicaid prospective payment: Case-mix increase

    Science.gov (United States)

    Baker, Samuel L.; Kronenfeld, Jennie J.

    1990-01-01

    South Carolina Medicaid implemented prospective payment by diagnosis-related group (DRG) for inpatient care. The rate of complications among newborns and deliveries doubled immediately. The case-mix index for newborns increased 66.6 percent, which increased the total Medicaid hospital expenditure 5.5 percent. Outlier payments increased total expenditure further. DRG distribution change among newborns has a large impact on spending because newborn complication DRGs have high weights. States adopting a DRG-based payment system for Medicaid should anticipate a greater increase in case mix than Medicare experienced. PMID:10113463

  20. Environmental effects of increased atmospheric carbon dioxide

    International Nuclear Information System (INIS)

    Soon, W.; Baliunas, S.L.; Robinson, A.B.; Robinson, Z.W.

    1999-01-01

    A review of the literature concerning the environmental consequences of increased levels of atmospheric carbon dioxide leads to the conclusion that increases during the 20th century have produced no deleterious effects upon global climate or temperature. Increased carbon dioxide has, however, markedly increased plant growth rates as inferred from numerous laboratory and field experiments. There is no clear evidence, nor unique attribution, of the global effects of anthropogenic CO 2 on climate. Meaningful integrated assessments of the environmental impacts of anthropogenic CO 2 are not yet possible because model estimates of global and regional climate changes on interannual, decadal and centennial timescales remain highly uncertain.(author)

  1. Loss of cytokine-STAT5 signaling in the CNS and pituitary gland alters energy balance and leads to obesity.

    Directory of Open Access Journals (Sweden)

    Ji-Yeon Lee

    Full Text Available Signal transducers and activators of transcription (STATs are critical components of cytokine signaling pathways. STAT5A and STAT5B (STAT5, the most promiscuous members of this family, are highly expressed in specific populations of hypothalamic neurons in regions known to mediate the actions of cytokines in the regulation of energy balance. To test the hypothesis that STAT5 signaling is essential to energy homeostasis, we used Cre-mediated recombination to delete the Stat5 locus in the CNS. Mutant males and females developed severe obesity with hyperphagia, impaired thermal regulation in response to cold, hyperleptinemia and insulin resistance. Furthermore, central administration of GM-CSF mediated the nuclear accumulation of STAT5 in hypothalamic neurons and reduced food intake in control but not in mutant mice. These results demonstrate that STAT5 mediates energy homeostasis in response to endogenous cytokines such as GM-CSF.

  2. P2X7 receptor inhibition increases CNTF in the subventricular zone, but not neurogenesis or neuroprotection after stroke in adult mice.

    Science.gov (United States)

    Kang, Seong Su; Keasey, Matthew Phillip; Hagg, Theo

    2013-10-01

    Increasing endogenous ciliary neurotrophic factor (CNTF) expression with a pharmacological agent might be beneficial after stroke as CNTF both promotes neurogenesis and, separately, is neuroprotective. P2X7 purinergic receptor inhibition is neuroprotective in rats and increases CNTF release in rat CMT1A Schwann cells. We, first, investigated the role of P2X7 in regulating CNTF and neurogenesis in adult mouse subventricular zone (SVZ). CNTF expression was increased by daily intravenous injections of the P2X7 antagonist Brilliant Blue G (BBG) in naïve C57BL/6 or Balb/c mice over 3 days. Despite the ∼40-60 % increase or decrease in CNTF with BBG or the agonist BzATP, respectively, the number of proliferated BrdU+SVZ nuclei did not change. BBG failed to increase FGF2, which is involved in CNTF-regulated neurogenesis, but induced IL-6, LIF, and EGF, which are known to reduce SVZ proliferation. Injections of IL-6 next to the SVZ induced CNTF and FGF2, but not proliferation, suggesting that IL-6 counteracts their neurogenesis-inducing effects. Following ischemic injury of the striatum by middle cerebral artery occlusion (MCAO), a 3-day BBG treatment increased CNTF in the medial penumbra containing the SVZ. BBG also induced CNTF and LIF, which are known to be protective following stroke, in the whole striatum after MCAO, but not GDNF or BDNF. However, BBG treatment did not reduce the lesion area or apoptosis in the penumbra. Even so, this study shows that P2X7 can be targeted with systemic drug treatments to differentially regulate neurotrophic factors in the brain following stroke.

  3. Interferon-β lipofection I. Increased efficacy of chemotherapeutic drugs on human tumor cells derived monolayers and spheroids.

    Science.gov (United States)

    Villaverde, M S; Gil-Cardeza, M L; Glikin, G C; Finocchiaro, L M E

    2012-07-01

    We evaluated the effect of hIFNβ gene transfer alone or in combination with different antineoplastic drugs commonly used in cancer treatment. Five human tumor-derived cell lines were cultured as monolayers and spheroids. Four cell lines (Ewing sarcomas EW7 and COH, melanoma M8 and mammary carcinoma MCF-7) were sensitive to hIFNβ gene lipofection. Although this effect appeared in both culture configurations, spheroids showed a relative multicellular resistance (insensitive colon carcinoma HT-29 excluded). EW7 and M8 hIFNβ-expressing cells were exposed to different concentrations of bleomycin, bortezomib, carboplatin, doxorubicin, etoposide, methotrexate, paclitaxel and vincristine in both configuration models. In chemotherapy-sensitive EW7 monolayers, the combination of hIFNβ gene and antineoplastic drugs displayed only additive or counteractive (methotrexate) effects, suggesting that cytotoxic mechanisms triggered by hIFNβ gene lipofection could be saturating the signaling pathways. Conversely, in chemotherapy-resistant EW7 spheroids or M8 cells, the combination of hIFNβ with drugs that mainly operate at the genotoxic level (doxorubicin, methotrexate and paclitaxel) presented only additive effects. However, drugs that also increase pro-oxidant species can complement the antitumor efficacy of the hIFNβ gene and clearly caused potentiated effects (bleomycin, bortezomib, carboplatin, etoposide and vincristine). The great bystander effect induced by hIFNβ gene lipofection could be among the main causes of its effectiveness, because only 1 or 2% of EW7 or M8 hIFNβ-expressing cells killed more than 60 or 80% of cell population, respectively.

  4. Rhynchophylline Protects Against the Amyloid β-Induced Increase of Spontaneous Discharges in the Hippocampal CA1 Region of Rats.

    Science.gov (United States)

    Shao, Hui; Mi, Ze; Ji, Wei-gang; Zhang, Cheng-huan; Zhang, Teng; Ren, Shuan-cheng; Zhu, Zhi-ru

    2015-11-01

    Accumulated soluble amyloid β (Aβ)-induced aberrant neuronal network activity has been recognized as a key causative factor leading to cognitive deficits which are the most outstanding characteristic of Alzheimer's disease (AD). As an important structure associated with learning and memory, the hippocampus is one of the brain regions that are impaired very early in AD, and the hippocampal CA1 region is selectively vulnerable to soluble Aβ oligomers. Our recent study showed that soluble Aβ1-42 oligomers induced hyperactivity and perturbed the firing patterns in hippocampal neurons. Rhynchophylline (RIN) is an important active tetracyclic oxindole alkaloid isolated from Uncaria rhynchophylla which is a traditional Chinese medicine and often used to treat central nervous system illnesses such as hypertension, convulsions, tremor, stroke etc. Previous evidence showed that RIN possessed neuroprotective effects of improving the cognitive function of mice with Alzheimer-like symptoms. In the present study, we aimed to investigate the protective effect of RIN against soluble Aβ1-42 oligomers-induced hippocampal hyperactivity. The results showed that (1) the mean frequency of spontaneous discharge was increased by the local application of 3 μM soluble Aβ1-42 oligomers; (2) 30 μM RIN did not exert any obvious effects on basal physiological discharges; and (3) treatment with RIN effectively inhibited the soluble Aβ1-42 oligomers-induced enhancement of spontaneous discharge, in a concentration-dependent manner with an IC50 = 9.0 μM. These in vivo electrophysiological results indicate that RIN can remold the spontaneous discharges disturbed by Aβ and counteract the deleterious effect of Aβ1-42 on neural circuit. The experimental findings provide further evidence to affirm the potential of RIN as a worthy candidate for further development into a therapeutic agent for AD.

  5. Increased adipose tissue lipolysis after a 2-week high-fat diet in sedentary overweight/obese men.

    Science.gov (United States)

    Howe, Harold R; Heidal, Kimberly; Choi, Myung Dong; Kraus, Ray M; Boyle, Kristen; Hickner, Robert C

    2011-07-01

    The purpose of this study was to determine if a high-fat diet would result in a higher lipolytic rate in subcutaneous adipose tissue than a lower-fat diet in sedentary nonlean men. Six participants (healthy males; 18-40 years old; body mass index, 25-37 kg/m(2)) underwent 2 weeks on a high-fat or well-balanced diet of similar energy content (approximately 6695 kJ) in randomized order with a 10-day washout period between diets. Subcutaneous abdominal adipose tissue lipolysis was determined over the course of a day using microdialysis after both 2-week diet sessions. Average interstitial glycerol concentrations (index of lipolysis) as determined using microdialysis were higher after the high-fat diet (210.8 ± 27.9 μmol/L) than after a well-balanced diet (175.6 ± 23.3 μmol/L; P = .026). There was no difference in adipose tissue microvascular blood flow as determined using the microdialysis ethanol technique. These results demonstrate that healthy nonlean men who diet on the high-fat plan have a higher lipolytic rate in subcutaneous abdominal adipose tissue than when they diet on a well-balanced diet plan. This higher rate of lipolysis may result in a higher rate of fat mass loss on the high-fat diet; however, it remains to be determined if this higher lipolytic rate in men on the high-fat diet results in a more rapid net loss of triglyceride from the abdominal adipose depots, or if the higher lipolytic rate is counteracted by an increased rate of lipid storage. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Lead uptake increases drought tolerance of wild type and transgenic poplar (Populus tremula x P. alba) overexpressing gsh 1.

    Science.gov (United States)

    Samuilov, Sladjana; Lang, Friedericke; Djukic, Matilda; Djunisijevic-Bojovic, Danijela; Rennenberg, Heinz

    2016-09-01

    Growth and development of plants largely depends on their adaptation ability in a changing climate. This is particularly true on heavy metal contaminated soils, but the interaction of heavy metal stress and climate on plant performance has not been intensively investigated. The aim of the present study was to elucidate if transgenic poplars (Populus tremula x P. alba) with enhanced glutathione content possess an enhanced tolerance to drought and lead (Pb) exposure (single and in combination) and if they are good candidates for phytoremediation of Pb contaminated soil. Lead exposure reduced growth and biomass accumulation only in above-ground tissue of wild type poplar, although most of lead accumulated in the roots. Drought caused a decline of the water content rather than reduced biomass production, while Pb counteracted this decline in the combined exposure. Apparently, metals such as Pb possess a protective function against drought, because they interact with abscisic acid dependent stomatal closure. Lead exposure decreased while drought increased glutathione content in leaves of both plant types. Lead accumulation was higher in the roots of transgenic plants, presumably as a result of chelation by glutathione. Water deprivation enhanced Pb accumulation in the roots, but Pb was subject to leakage out of the roots after re-watering. Transgenic plants showed better adaptation under mild drought plus Pb exposure partially due to improved glutathione synthesis. However, the transgenic plants cannot be considered as a good candidate for phytoremediation of Pb, due to its small translocation to the shoots and its leakage out of the roots upon re-watering. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Cerebellar anodal tDCS increases implicit learning when strategic re-aiming is suppressed in sensorimotor adaptation.

    Science.gov (United States)

    Leow, Li-Ann; Marinovic, Welber; Riek, Stephan; Carroll, Timothy J

    2017-01-01

    Neurophysiological and neuroimaging work suggests that the cerebellum is critically involved in sensorimotor adaptation. Changes in cerebellar function alter behaviour when compensating for sensorimotor perturbations, as shown by non-invasive stimulation of the cerebellum and studies involving patients with cerebellar degeneration. It is known, however, that behavioural responses to sensorimotor perturbations reflect both explicit processes (such as volitional aiming to one side of a target to counteract a rotation of visual feedback) and implicit, error-driven updating of sensorimotor maps. The contribution of the cerebellum to these explicit and implicit processes remains unclear. Here, we examined the role of the cerebellum in sensorimotor adaptation to a 30° rotation of visual feedback of hand position during target-reaching, when the capacity to use explicit processes was manipulated by controlling movement preparation times. Explicit re-aiming was suppressed in one condition by requiring subjects to initiate their movements within 300ms of target presentation, and permitted in another condition by requiring subjects to wait approximately 1050ms after target presentation before movement initiation. Similar to previous work, applying anodal transcranial direct current stimulation (tDCS; 1.5mA) to the right cerebellum during adaptation resulted in faster compensation for errors imposed by the rotation. After exposure to the rotation, we evaluated implicit remapping in no-feedback trials after providing participants with explicit knowledge that the rotation had been removed. Crucially, movements were more adapted in these no-feedback trials following cerebellar anodal tDCS than after sham stimulation in both long and short preparation groups. Thus, cerebellar anodal tDCS increased implicit remapping during sensorimotor adaptation, irrespective of preparation time constraints. The results are consistent with the possibility that the cerebellum contributes to the

  8. Increase nuclear safety of WWER-440

    International Nuclear Information System (INIS)

    Nochev, T.; Sabinov, S.

    2000-01-01

    A complete program for increasing nuclear safety has been made at NPP Kozloduy with the participation of German, French, Russian and American specialists. This effort cost greater than 100 mil $. This report includes the methods of increasing nuclear safety. The style of management in NPP Kozloduy has been changed for the last seven years. (authors)

  9. A Work Schedule to Increase Productivity.

    Science.gov (United States)

    Atwood, Caleb S.

    1979-01-01

    Outlines a technique for making a tight economy and energy shortages more palatable by supplementing employee wage increases with benefits such as alternative three and four day "weekends" without loss of regular pay and by enabling business to increase profits. (Author/IRT)

  10. Effect of increasing truck weight on bridges.

    Science.gov (United States)

    2010-09-01

    Legislation has been proposed that will allow a 17,000 lb increase in the maximum gross vehicle : weight on the Interstate Highway System. This projects main goal is quantify the effect of this : increase on the internal forces to which typical sl...

  11. Increased greenhouse effect substantiated through measurements

    International Nuclear Information System (INIS)

    Skartveit, Arvid

    2001-01-01

    The article presents studies on the greenhouse effect which substantiates the results from satellite measurements during the period 1970 - 1997. These show an increased effect due to increase in the concentration of the climatic gases CO 2 , methane, CFC-11 and CFC-12 in the atmosphere

  12. increases in cross-sectional samples

    African Journals Online (AJOL)

    1971-03-27

    Mar 27, 1971 ... TABLE Ill. PERCE 'TAGE INCREASES IN BODY M EASU REM ENTS .... population means (polynomials) for calculating total per- ... with age in males, except for very small increases in Bantu. ..... this applies at high levels of energy expenditure is another .... available for adults of all 4 populations studied.

  13. Dihydrotestostenone increase the gene expression of androgen ...

    African Journals Online (AJOL)

    HNTEP cells were grown in basal medium and treated with DHT in different conditions. HNTEP cells under treatment with DHT (10-13 M) induced an increase in FHL-2 expression. In turn, high DHT concentrations (10-8 M) induced an increase in the expression SHP-1. The present data suggest that the SHP-1 and FHL-2 ...

  14. Effective Strategies for Increasing Citation Frequency

    Science.gov (United States)

    Ebrahim, Nader Ale; Salehi, Hadi; Embi, Mohamed Amin; Tanha, Farid Habibi; Gholizadeh, Hossein; Motahar, Seyed Mohammad; Ordi, Ali

    2013-01-01

    Due to the effect of citation impact on The Higher Education (THE) world university ranking system, most of the researchers are looking for some helpful techniques to increase their citation record. This paper by reviewing the relevant articles extracts 33 different ways for increasing the citations possibilities. The results show that the article…

  15. Worldwide Increasing Incidences of Cutaneous Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Dianne E. Godar

    2011-01-01

    Full Text Available The incidence of cutaneous malignant melanoma (CMM has been increasing at a steady rate in fair-skinned populations around the world for decades. Scientists are not certain why CMM has been steadily increasing, but strong, intermittent UVB (290–320 nm exposures, especially sunburn episodes, probably initiate, CMM, while UVA (321–400 nm passing through glass windows in offices and cars probably promotes it. The CMM incidence may be increasing at an exponential rate around the world, but it definitely decreases with increasing latitude up to ~50°N where it reverses and increases with the increasing latitude. The inversion in the incidence of CMM may occur because there is more UVA relative to UVB for most of the year at higher latitudes. If windows, allowing UVA to enter our indoor-working environment and cars, are at least partly responsible for the increasing incidence of CMM, then UV filters can be applied to reduce the rate of increase worldwide.

  16. Reading Instruction That Increases Thinking Abilities.

    Science.gov (United States)

    Collins, Cathy

    1991-01-01

    Analyzes the effects of eight reading and writing lessons designed to increase adolescent thinking ability. Finds that the lessons increased thinking abilities and scholastic achievement of middle school students. Notes that the lessons positively affect students' self-esteem and communication skills. (RS)

  17. Cyberbullying: An Increasing Challenge for Schools

    Science.gov (United States)

    von Marees, Nandoli; Petermann, Franz

    2012-01-01

    The use of information and communication technology (ICT) has not only brought advantages to mankind. One downside is the emergence and increase of cyberbullying in schools. Affecting students of all ages, teachers, parents, and other educators, this special form of bullying is an increasing challenge for schools. This article offers an overview…

  18. The anti-oxidative transcription factor Nuclear factor E2 related factor-2 (Nrf2) counteracts TGF-β1 mediated growth inhibition of pancreatic ductal epithelial cells -Nrf2 as determinant of pro-tumorigenic functions of TGF-β1

    International Nuclear Information System (INIS)

    Genrich, Geeske; Kruppa, Marcus; Lenk, Lennart; Helm, Ole; Broich, Anna; Freitag-Wolf, Sandra; Röcken, Christoph; Sipos, Bence; Schäfer, Heiner; Sebens, Susanne

    2016-01-01

    Nrf2-mediated cell survival was predominantly based on an enhanced proliferative activity. Accordingly, expression of p21 expression along with expression of phospho-p38 and phospho-Smad3 was diminished whereas Erk-phosphorylation was enhanced under these conditions. Overall, our data demonstrate that Nrf2 being elevated in early precursor lesions counteracts the growth inhibiting function of TGF-β1 already in benign and premalignant pancreatic ductal epithelial cells. This could represent one fundamental mechanism underlying the functional switch of both- TGF-β1 and Nrf2 – which may manifest already in early stages of PDAC development. The online version of this article (doi:10.1186/s12885-016-2191-7) contains supplementary material, which is available to authorized users

  19. Exercising self-control increases approach motivation.

    Science.gov (United States)

    Schmeichel, Brandon J; Harmon-Jones, Cindy; Harmon-Jones, Eddie

    2010-07-01

    The present research tested the hypothesis that exercising self-control causes an increase in approach motivation. Study 1 found that exercising (vs. not exercising) self-control increases self-reported approach motivation. Study 2a identified a behavior--betting on low-stakes gambles--that is correlated with approach motivation but is relatively uncorrelated with self-control, and Study 2b observed that exercising self-control temporarily increases this behavior. Last, Study 3 found that exercising self-control facilitates the perception of a reward-relevant symbol (i.e., a dollar sign) but not a reward-irrelevant symbol (i.e., a percent sign). Altogether, these results support the hypothesis that exercising self-control temporarily increases approach motivation. Failures of self-control that follow from prior efforts at self-control (i.e., ego depletion) may be explained in part by increased approach motivation.

  20. Nuclear programs see a qualified increase

    International Nuclear Information System (INIS)

    Anon.

    1995-01-01

    This March 1995 Nuclear News article is a review of the proposed DOE budget for nuclear energy activities. This proposed budget increases spending by 32.7% and includes increases in nearly every individual program except civilian reactor development. Isotope production and distribution receive the largest increase, followed by termination costs for certain federal reactor projects. There is a 61.9% proposed increase (to $199M) for waste management activities, but with funding from other Departments, the actual budget would be $612M. The majority of this money would go toward Yucca Mountain activities. Except for the cancellation of the Advanced Neutron Source, the Science and Technology portion of the budget shows an overall small increase

  1. Are increases in cigarette taxation regressive?

    Science.gov (United States)

    Borren, P; Sutton, M

    1992-12-01

    Using the latest published data from Tobacco Advisory Council surveys, this paper re-evaluates the question of whether or not increases in cigarette taxation are regressive in the United Kingdom. The extended data set shows no evidence of increasing price-elasticity by social class as found in a major previous study. To the contrary, there appears to be no clear pattern in the price responsiveness of smoking behaviour across different social classes. Increases in cigarette taxation, while reducing smoking levels in all groups, fall most heavily on men and women in the lowest social class. Men and women in social class five can expect to pay eight and eleven times more of a tax increase respectively, than their social class one counterparts. Taken as a proportion of relative incomes, the regressive nature of increases in cigarette taxation is even more pronounced.

  2. Employee responses to health insurance premium increases.

    Science.gov (United States)

    Goldman, Dana P; Leibowitz, Arleen A; Robalino, David A

    2004-01-01

    To determine the sensitivity of employees' health insurance decisions--including the decision to not choose health maintenance organization or fee-for-service coverage--during periods of rapidly escalating healthcare costs. A retrospective cohort study of employee plan choices at a single large firm with a "cafeteria-style" benefits plan wherein employees paid all the additional cost of purchasing more generous insurance. We modeled the probability that an employee would drop coverage or switch plans in response to employee premium increases using data from a single large US company with employees across 47 states during the 3-year period of 1989 through 1991, a time of large premium increases within and across plans. Premium increases induced substantial plan switching. Single employees were more likely to respond to premium increases by dropping coverage, whereas families tended to switch to another plan. Premium increases of 10% induced 7% of single employees to drop or severely cut back on coverage; 13% to switch to another plan; and 80% to remain in their existing plan. Similar figures for those with family coverage were 11%, 12%, and 77%, respectively. Simulation results that control for known covariates show similar increases. When faced with a dramatic increase in premiums--on the order of 20%--nearly one fifth of the single employees dropped coverage compared with 10% of those with family coverage. Employee coverage decisions are sensitive to rapidly increasing premiums, and single employees may be likely to drop coverage. This finding suggests that sustained premium increases could induce substantial increases in the number of uninsured individuals.

  3. Atrial natriuretic factor increases vascular permeability

    International Nuclear Information System (INIS)

    Lockette, W.; Brennaman, B.

    1990-01-01

    An increase in central blood volume in microgravity may result in increased plasma levels of atrial natriuretic factor (ANF). Since elevations in plasma ANF are found in clinical syndromes associated with edema, and since space motion sickness induced by microgravity is associated with an increase in central blood volume and facial edema, we determined whether ANF increases capillary permeability to plasma protein. Conscious, bilaterally nephrectomized male rats were infused with either saline, ANF + saline, or hexamethonium + saline over 2 h following bolus injections of 125I-albumin and 14C-dextran of similar molecular size. Blood pressure was monitored and serial determinations of hematocrits were made. Animals infused with 1.0 micrograms.kg-1.min-1 ANF had significantly higher hematocrits than animals infused with saline vehicle. Infusion of ANF increased the extravasation of 125I-albumin, but not 14C-dextran from the intravascular compartment. ANF also induced a depressor response in rats, but the change in blood pressure did not account for changes in capillary permeability to albumin; similar depressor responses induced by hexamethonium were not accompanied by increased extravasation of albumin from the intravascular compartment. ANF may decrease plasma volume by increasing permeability to albumin, and this effect of ANF may account for some of the signs and symptoms of space motion sickness

  4. Increasing trends of herpes zoster in Australia.

    Directory of Open Access Journals (Sweden)

    Raina MacIntyre

    Full Text Available Increasing trends in incidence of herpes zoster (HZ have been reported in Australia and internationally. This may reflect the impact of childhood VZV vaccination programs introduced universally in Australia in late 2005. The objective of this study was to evaluate changes in incidence of HZ and PHN in Australia over time, and associated healthcare resource utilisation.Australian data on general practice (GP encounters for HZ, specific antiviral prescribing data from the pharmaceutical benefits scheme, emergency department presentations from the states of NSW and Victoria and national hospitalisation data for HZ were analysed for time trends using regression models. Two time periods (2000-2006 and 2006-2013 were compared which correspond broadly with the pre- and post- universal VZV vaccination period.All data sources showed increasing rates of HZ with age and over time. The GP database showed a significant annual increase in encounters for HZ of 2.5 per 100,000 between 1998 and 2013, and the rates of prescriptions for HZ increased by 4.2% per year between 2002 and 2012. In the 60+ population HZ incidence was estimated to increase from 11.9 to 15.4 per 1,000 persons using GP data or from 12.8 to 14.2 per 1,000 persons using prescription data (p<0.05, between the two periods. Hospitalisation data did not show the same increasing trend over time, except for the age group ≥80 years. Most emergency visits for HZ were not admitted, and showed significant increases over time.The burden of HZ in Australia is substantial, and continues to increase over time. This increase is seen both pre- and post-universal VZV vaccination in 2005, and is most prominent in the older population. The substantial burden of HZ, along with ageing of the Australian population and the importance of healthy ageing, warrants consideration of HZ vaccination for the elderly.

  5. Idaho Power's reverses decline with employee increase

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    Following several years of decline, the number of full-time Idaho Power employees increased to 1,528 at the end of 1989, up from 1,500 in 1988. The increase reversed a steady decline that began in 1984 when the company had a peak employment of 1,725. Last year's increase in the work force in part reflects recent additions in customers served and the electric demands of an expanding economy in the service area, as well as new regulatory requirements, the company said

  6. FEASIBILITY OF INCREASING THE ENERGY OF RHIC

    International Nuclear Information System (INIS)

    MACKAY, W.W.; JAIN, A.; LUCCIO, A.U.; PILAT, F.; ROSER, T.; TEPIKIAN, S.; TROBOJEVIC, D.

    2001-01-01

    In this paper we discuss the possibility of increasing the energy of beams in RHIC by as much as 30% with a modest trade-off in luminosity. The arc dipoles and quadrupoles were designed with considerable margin. For higher energies (>100 GeV/nucleon) the minimum β* may be required to increase as the interaction region triplets saturate. The separator magnets (DX) have the least margin for increased field, so we consider three scenarios: allowing for a small crossing angle with the present DX magnets, upgrading the DX magnets to higher strength, and permitting a crossing angle of ∼1degree by removing the DX magnets altogether

  7. Increasing atmospheric carbon dioxide and its consequences

    Energy Technology Data Exchange (ETDEWEB)

    Lockwood, J G

    1982-09-16

    The effects of increasing CO/sub 2/ concentrations in the atmosphere are estimated using general circulation models (GCMs), which have the ability to portray many of the nonlinear feedback processes which serve to regulate atmospheric (and hence climatic) changes. GCMs predict that a doubling of atmospheric CO/sub 2/ would result in a 2-3 k increase of globally averaged surface air temperature. The largest warming will occur in the winter in high latitudes. Detection studies are now being directed towards isolating those parts of observed climate fluctuations that are attributable to increasing atmospheric CO/sub 2/. (KRM)

  8. The Aging Kidney: Increased Susceptibility to Nephrotoxicity

    Science.gov (United States)

    Wang, Xinhui; Bonventre, Joseph V.; Parrish, Alan R.

    2014-01-01

    Three decades have passed since a series of studies indicated that the aging kidney was characterized by increased susceptibility to nephrotoxic injury. Data from these experimental models is strengthened by clinical data demonstrating that the aging population has an increased incidence and severity of acute kidney injury (AKI). Since then a number of studies have focused on age-dependent alterations in pathways that predispose the kidney to acute insult. This review will focus on the mechanisms that are altered by aging in the kidney that may increase susceptibility to injury, including hemodynamics, oxidative stress, apoptosis, autophagy, inflammation and decreased repair. PMID:25257519

  9. Who Benefits from a Minimum Wage Increase?

    OpenAIRE

    John W. Lopresti; Kevin J. Mumford

    2015-01-01

    This paper addresses the question of how a minimum wage increase affects the wages of low-wage workers. Most studies assume that there is a simple mechanical increase in the wage for workers earning a wage between the old and the new minimum wage, with some studies allowing for spillovers to workers with wages just above this range. Rathe