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Sample records for counteracts gm-csf-mediated increase

  1. SHP-1 phosphatase activity counteracts increased T cell receptor affinity.

    Science.gov (United States)

    Hebeisen, Michael; Baitsch, Lukas; Presotto, Danilo; Baumgaertner, Petra; Romero, Pedro; Michielin, Olivier; Speiser, Daniel E; Rufer, Nathalie

    2013-03-01

    Anti-self/tumor T cell function can be improved by increasing TCR-peptide MHC (pMHC) affinity within physiological limits, but paradoxically further increases (K(d) affinity for the tumor antigen HLA-A2/NY-ESO-1, we investigated the molecular mechanisms underlying this high-affinity-associated loss of function. As compared with cells expressing TCR affinities generating optimal function (K(d) = 5 to 1 μM), those with supraphysiological affinity (K(d) = 1 μM to 15 nM) showed impaired gene expression, signaling, and surface expression of activatory/costimulatory receptors. Preferential expression of the inhibitory receptor programmed cell death-1 (PD-1) was limited to T cells with the highest TCR affinity, correlating with full functional recovery upon PD-1 ligand 1 (PD-L1) blockade. In contrast, upregulation of the Src homology 2 domain-containing phosphatase 1 (SHP-1/PTPN6) was broad, with gradually enhanced expression in CD8(+) T cells with increasing TCR affinities. Consequently, pharmacological inhibition of SHP-1 with sodium stibogluconate augmented the function of all engineered T cells, and this correlated with the TCR affinity-dependent levels of SHP-1. These data highlight an unexpected and global role of SHP-1 in regulating CD8(+) T cell activation and responsiveness and support the development of therapies inhibiting protein tyrosine phosphatases to enhance T cell-mediated immunity.

  2. N-Acylethanolamine-hydrolyzing acid amidase inhibition increases colon N-palmitoylethanolamine levels and counteracts murine colitis

    Science.gov (United States)

    Alhouayek, Mireille; Bottemanne, Pauline; Subramanian, Kumar V.; Lambert, Didier M.; Makriyannis, Alexandros; Cani, Patrice D.; Muccioli, Giulio G.

    2015-01-01

    N-Palmitoylethanolamine or palmitoylethanolamide (PEA) is an anti-inflammatory compound that was recently shown to exert peroxisome proliferator-activated receptor-α-dependent beneficial effects on colon inflammation. The actions of PEA are terminated following hydrolysis by 2 enzymes: fatty acid amide hydrolase (FAAH), and the less-studied N-acylethanolamine-hydrolyzing acid amidase (NAAA). This study aims to investigate the effects of inhibiting the enzymes responsible for PEA hydrolysis in colon inflammation in order to propose a potential therapeutic target for inflammatory bowel diseases (IBDs). Two murine models of IBD were used to assess the effects of NAAA inhibition, FAAH inhibition, and PEA on macroscopic signs of colon inflammation, macrophage/neutrophil infiltration, and the expression of proinflammatory mediators in the colon, as well as on the colitis-related systemic inflammation. NAAA inhibition increases PEA levels in the colon and reduces colon inflammation and systemic inflammation, similarly to PEA. FAAH inhibition, however, does not increase PEA levels in the colon and does not affect the macroscopic signs of colon inflammation or immune cell infiltration. This is the first report of an anti-inflammatory effect of a systemically administered NAAA inhibitor. Because NAAA is the enzyme responsible for the control of PEA levels in the colon, we put forth this enzyme as a potential therapeutic target in chronic inflammation in general and IBD in particular.—Alhouayek, M., Bottemanne, P., Subramanian, K. V., Lambert, D. M., Makriyannis, A., Cani, P. D., and Muccioli, G. G. N-Acylethanolamine-hydrolyzing acid amidase inhibition increases colon N-palmitoylethanolamine levels and counteracts murine colitis. PMID:25384424

  3. CNF1 increases brain energy level, counteracts neuroinflammatory markers and rescues cognitive deficits in a murine model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Stefano Loizzo

    Full Text Available Overexpression of pro-inflammatory cytokines and cellular energy failure are associated with neuroinflammatory disorders, such as Alzheimer's disease. Transgenic mice homozygous for human ApoE4 gene, a well known AD and atherosclerosis animal model, show decreased levels of ATP, increased inflammatory cytokines level and accumulation of beta amyloid in the brain. All these findings are considered responsible for triggering cognitive decline. We have demonstrated that a single administration of the bacterial E. coli protein toxin CNF1 to aged apoE4 mice, beside inducing a strong amelioration of both spatial and emotional memory deficits, favored the cell energy restore through an increment of ATP content. This was accompanied by a modulation of cerebral Rho and Rac1 activity. Furthermore, CNF1 decreased the levels of beta amyloid accumulation and interleukin-1β expression in the hippocampus. Altogether, these data suggest that the pharmacological modulation of Rho GTPases by CNF1 can improve memory performances in an animal model of Alzheimer's disease via a control of neuroinflammation and a rescue of systemic energy homeostasis.

  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

    Directory of Open Access Journals (Sweden)

    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. 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.

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

    Directory of Open Access Journals (Sweden)

    Greta Jakobsdottir

    Full Text Available INTRODUCTION: 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. OBJECTIVE: 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. MATERIAL AND METHODS: 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. RESULTS AND DISCUSSION: 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.

  7. Myogenic constriction is increased in mesenteric resistance arteries from rats with chronic heart failure : instantaneous counteraction by acute AT(1) receptor blockade

    NARCIS (Netherlands)

    Gschwend, S; Henning, RH; Pinto, YM; de Zeeuw, D; van Gilst, WH; Buikema, H

    2003-01-01

    1 Increased vascular resistance in chronic heart failure (CHF) has been attributed to stimulated neurohumoral systems. However, local mechanisms may also importantly contribute to set arterial tone. Our aim, therefore, was to test whether pressure-induced myogenic constriction of resistance arteries

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

    DEFF Research Database (Denmark)

    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...

  9. 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...... which implies a destruction of capital that will counteract the falling rate of profit. This will require sustained political intervention....

  10. To what extent can cirrus seeding counteract global warming?

    Science.gov (United States)

    Gasparini, Blaz; Lohmann, Ulrike

    2017-04-01

    The idea of modifying cirrus clouds to directly counteract greenhouse gas warming has gained a lot of momentum in recent years, despite large disputes over its physical feasibility. We use the ECHAM-HAM general circulation model to evaluate the temperature and precipitation responses to cirrus thinning by seeding with efficient ice nucleating particles and increasing ice crystal sedimentation velocities in a 1.5xCO2 world. The seeding scenario can counteract about 40% of the warming and precipitation increase induced by 1.5 x CO2 concentrations with respect to present day values. The idealized ice crystal sedimentation velocity increase scenario on the other hand fully restores the global annual temperature but counteracts only half of the precipitation increase. Moreover, we define a climate damage function, quadratic in temperature and precipitation anomalies to calculate the damage of the different scenarios in 21 selected land regions. Seeding can decrease about 55% of the CO2 induced damage, while the sedimentation velocity increase can counteract about 95% of the damage. A regional analysis shows the negative responses of seeding are minimal both in terms of precipitation and temperature, which makes cirrus seeding an attractive geoengineering method.

  11. Increased chemical weathering of olivine in high-energy shelf seas can counteract human CO2 emissions and ocean acidification against a price well below that of CCS and other methods

    Science.gov (United States)

    de Boer, Poppe L.; Schuiling, Roelof D.

    2014-05-01

    In the reaction: Mg(Fe)2SiO4 (olivine) + 4 H2O 2 Mg(Fe)2+ + 4 OH- + H4SiO4, followed by 4 OH- + 4 CO2 4 HCO3-, CO2 is consumed, and Mg2+, Fe2+, H4SiO4 and HCO3- are produced. Contrary to the paradigm that olivine weathering in nature is a slow process, flume experiments show a fast reaction, consuming CO2, and raising the pH at short notice. Only under static conditions a silica coating develops that retards the reaction. In high-energy shallow marine environments such silica coatings are abraded so that the chemical reaction can continue. When kept in motion even large olivine grains and gravels, rubbing and bumping against each other and against other sediment grains, weather quickly. Experiments show that fine micron- to silt-sized olivine particles are produced, and that the chemical reaction is fast. The chemical weathering of 7 km3 olivine is needed on a yearly basis in order to compensate the human CO2 emissions. This seems much, but is of the same order of magnitude as the volume of fossil fuels (in oil equivalents ~10 km3) that are burnt annually. Olivine is readily available at the Earth' surface on all continents, and such volume of 7 km3 is exceeded by existing mines; e.g. the Bingham Canyon open pit mine in Utah has an excavated volume of 25 km3. Hydrocarbons, on the other hand, are commonly retrieved with great efforts, from great depths, and often at remote locations. Spreading of large amounts of olivine (and/or serpentinite) in high-energy shelf seas where coarse sand and gravel can be transported, will counteract human CO2 production by fossil fuel burning and ocean acidification against a price well below that of other methods; order of US 10.- per ton CO2. For example part of the continental shelf between the Shetland Isles and France, that is the Southern Bight of the North Sea, the English Channel and the Irish Sea, is covered with sand waves, and in and around the English Channel an area of well over 100,000 km2 experiences bed shear stresses

  12. Electrical stimulation counteracts muscle decline in seniors.

    Science.gov (United States)

    Kern, Helmut; Barberi, Laura; Löfler, Stefan; Sbardella, Simona; Burggraf, Samantha; Fruhmann, Hannah; Carraro, Ugo; Mosole, Simone; Sarabon, Nejc; Vogelauer, Michael; Mayr, Winfried; Krenn, Matthias; Cvecka, Jan; Romanello, Vanina; Pietrangelo, Laura; Protasi, Feliciano; Sandri, Marco; Zampieri, Sandra; Musaro, Antonio

    2014-01-01

    The loss in muscle mass coupled with a decrease in specific force and shift in fiber composition are hallmarks of aging. Training and regular exercise attenuate the signs of sarcopenia. However, pathologic conditions limit the ability to perform physical exercise. We addressed whether electrical stimulation (ES) is an alternative intervention to improve muscle recovery and defined the molecular mechanism associated with improvement in muscle structure and function. We analyzed, at functional, structural, and molecular level, the effects of ES training on healthy seniors with normal life style, without routine sport activity. ES was able to improve muscle torque and functional performances of seniors and increased the size of fast muscle fibers. At molecular level, ES induced up-regulation of IGF-1 and modulation of MuRF-1, a muscle-specific atrophy-related gene. ES also induced up-regulation of relevant markers of differentiating satellite cells and of extracellular matrix remodeling, which might guarantee shape and mechanical forces of trained skeletal muscle as well as maintenance of satellite cell function, reducing fibrosis. Our data provide evidence that ES is a safe method to counteract muscle decline associated with aging.

  13. ISG15 counteracts Listeria monocytogenes infection

    Science.gov (United States)

    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

  14. Training users to counteract phishing.

    Science.gov (United States)

    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.

  15. 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.

  16. 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.

  17. 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. PMID:28128327

  18. PA3297 Counteracts Antimicrobial Effects of Azithromycin in Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Hao eTan

    2016-03-01

    Full Text Available Pseudomonas aeruginosa causes acute and chronic infections in human. Its increasing resistance to antibiotics requires alternative treatments that are more effective than available strategies. Among the alternatives is the unconventional usage of conventional antibiotics, of which the macrolide antibiotic azithromycin (AZM provides a paradigmatic example. AZM therapy is associated with a small but consistent improvement in respiratory function of cystic fibrosis (CF patients suffering from chronic P. aeruginosa infection. Besides immunomodulating activities, AZM represses bacterial genes involved in virulence, quorum sensing, biofilm formation, and motility, all of which are due to stalling of ribosome and depletion of cellular tRNA pool. However, how P. aeruginosa responds to and counteracts the effects of AZM remain elusive. Here we found that deficiency of PA3297, a gene encoding a DEAH-box helicase, intensified AZM-mediated bacterial killing, suppression of pyocyanin production and swarming motility, and hypersusceptibility to hydrogen peroxide. We demonstrated that expression of PA3297 is induced by the interaction between AZM and ribosome. Importantly, mutation of PA3297 resulted in elevated levels of unprocessed 23S-5S rRNA in the presence of AZM, which might lead to increased susceptibility to AZM-mediated effects. Our results revealed one of the bacterial responses in counteracting the detrimental effects of AZM.

  19. Discourse on corruption counteraction in network trade

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    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

  20. [Non-indicated cesarean section--does the "Golem" counteract?].

    Science.gov (United States)

    Herman, Arie

    2011-11-01

    Cesarean section rate is steadily increasing and in Israel it has risen to 20%. MultipLe and different reasons have led to this phenomenon, among them are non-indicated cesarean sections. Although health care providers disagree whether this development is medically, ethically and publically justified, national associations allow it, while respecting those obstetricians who decline to do so. In Israel there are some hospitals which allow non-indicated cesarean sections, whereas others reject them. When discussing this issue with the patients, documentation is advised concerning the reasons for approval or rejection of the patients' request in order to avoid future complaints in the case of adverse outcome. Low risk vaginal delivery should be regarded as a natural process and not as a medical treatment and keeping balanced and reasonable decisions may help to contain the phenomenon and avoid a situation in which the "Golem" created by the medical system, counteracts.

  1. Icaritin requires Phosphatidylinositol 3 kinase (PI3K)/Akt signaling to counteract skeletal muscle atrophy following mechanical unloading

    OpenAIRE

    ZHANG, Zong-Kang; Li, Jie; Liu, Jin; Baosheng GUO; Leung, Albert; Zhang, Ge; Zhang, Bao-Ting

    2016-01-01

    Counteracting muscle atrophy induced by mechanical unloading/inactivity is of great clinical need and challenge. A therapeutic agent that could counteract muscle atrophy following mechanical unloading in safety is desired. This study showed that natural product Icaritin (ICT) could increase the phosphorylation level of Phosphatidylinositol 3 kinase (PI3K) at p110 catalytic subunit and promote PI3K/Akt signaling markers in C2C12 cells. This study further showed that the high dose ICT treatment...

  2. More reflectivity for the soil to counteract the global-warming of the Earth

    OpenAIRE

    Tejedor, A; Pacheco, A. F.

    2009-01-01

    It is argued that a dedicated effort to increase the reflectivity of the surface of our planet by means of, for example, metallic plates would induce an increase in the global albedo which would counteract in part the present global-warming process of the Earth. This could alleviate the urgency of reducing the CO2 emissions. The City of Zaragoza (Spain) is chosen to illustrate the likelihood of our arguments.

  3. Electrical stimulation (ES counteracts muscle decline in seniors

    Directory of Open Access Journals (Sweden)

    Helmut eKern

    2014-07-01

    Full Text Available The loss in muscle mass coupled with a decrease in specific force and shift in fiber composition are all marks of aging. Training and regular exercise attenuate the signs of sarcopenia. However, pathologic conditions limit the ability to perform physical exercise.We addressed whether electrical stimulation (ES is an alternative intervention to improve muscle recovery and defined the molecular mechanism associated with improvement in muscle structure and function.We analyzed, at functional, structural, and molecular level, the effects of ES training on healthy seniors with normal life style, without routine sport activity.ES was able to improve muscle torque and functional performances of seniors and increased the size of fast muscle fibers. At molecular level, ES induced up-regulation of IGF-1 and modulation of MuRF1, a muscle-specific atrophy-related gene. ES also induced up-regulation of relevant markers of differentiating satellite cells and of extracellular matrix remodeling, which might guarantee shape and mechanical forces of trained skeletal muscle as well as maintenance of satellite cell function, reducing fibrosis.Our data provide evidence that ES is a safe method to counteract muscle decline associated with aging.

  4. The beneficial effects of taurine to counteract sarcopenia.

    Science.gov (United States)

    Scicchitano, Bianca M; Sica, Gigliola

    2016-11-22

    Aging is a multifactorial process characterized by several features including low-grade inflammation, increased oxidative stress and reduced regenerative capacity, which ultimately lead to alteration in morpho-functional properties of skeletal muscle, thus promoting sarcopenia. This condition is characterized by a gradual loss of muscle mass due to an unbalance between protein synthesis and degradation, finally conveying in functional decline and disability. The development of specific therapeutic approaches able to block or reverse this condition may represent an invaluable tool for the promotion of a healthy aging among elderly. It is well established that changes in the quantity and the quality of dietary proteins, as well as the intake of specific amino acids, are able to counteract some of the physiopathological processes related to the progression of the loss of muscle mass and may have beneficial effects in improving the anabolic response of muscle in the elderly. Taurine is a non-essential amino acid expressed in high concentration in several mammalian tissues and particularly in skeletal muscle where it is involved in the modulation of intracellular calcium concentration and ion channel regulation and where it also acts as an antioxidant and anti-inflammatory factor. The aim of this review is to summarize the pleiotropic effects of taurine on specific muscle targets and to discuss its role in regulating signaling pathways involved in the maintenance of muscle homeostasis. We also highlight the potential use of taurine as a therapeutic molecule for the amelioration of skeletal muscle function and performance severely compromised during aging.

  5. Anti-cancer agents counteracting tumor glycolysis

    OpenAIRE

    Granchi, Carlotta; Minutolo, Filippo

    2012-01-01

    Can we consider cancer as a “metabolic disease”? Tumors are the result of a metabolic selection, forming tissues composed of heterogeneous cells that generally express an overactive metabolism as a common feature. In fact, cancer cells have to deal with increased needs for both energy and biosynthetic intermediates, in order to support their growth and invasiveness. However, their high proliferation rate often generates regions that are not sufficiently oxygenated. Therefore, their carbohydra...

  6. 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,…

  7. In COS cells Vpu can both stabilize tetherin expression and counteract its antiviral activity.

    Science.gov (United States)

    Waheed, Abdul A; Kuruppu, Nishani D; Felton, Kathryn L; D'Souza, Darren; Freed, Eric O

    2014-01-01

    The interferon-inducible cellular protein tetherin (CD317/BST-2) inhibits the release of a broad range of enveloped viruses. The HIV-1 accessory protein Vpu enhances virus particle release by counteracting this host restriction factor. While the antagonism of human tetherin by Vpu has been associated with both proteasomal and lysosomal degradation, the link between Vpu-mediated tetherin degradation and the ability of Vpu to counteract the antiviral activity of tetherin remains poorly understood. Here, we show that human tetherin is expressed at low levels in African green monkey kidney (COS) cells. However, Vpu markedly increases tetherin expression in this cell line, apparently by sequestering it in an internal compartment that bears lysosomal markers. This stabilization of tetherin by Vpu requires the transmembrane sequence of human tetherin. Although Vpu stabilizes human tetherin in COS cells, it still counteracts the ability of tetherin to suppress virus release. The enhancement of virus release by Vpu in COS cells is associated with a modest reduction in cell-surface tetherin expression, even though the overall expression of tetherin is higher in the presence of Vpu. This study demonstrates that COS cells provide a model system in which Vpu-mediated enhancement of HIV-1 release is uncoupled from Vpu-mediated tetherin degradation.

  8. Forest management could counteract distribution retractions forced by climate change.

    Science.gov (United States)

    Mair, Louise; Harrison, Philip J; Räty, Minna; Bärring, Lars; Strandberg, Gustav; Snäll, Tord

    2017-03-28

    Climate change is expected to drive the distribution retraction of northern species. However, particularly in regions with a history of intensive exploitation, changes in habitat management could facilitate distribution expansions counter to expectations under climate change. Here, we test the potential for future forest management to facilitate the southwards expansion of an old-forest species from the boreal region into the boreo-nemoral region, contrary to expectations under climate change. We used an ensemble of species distribution models based on citizen science data to project the response of Phellinus ferrugineofuscus, a red-listed old-growth indicator, wood-decaying fungus, to six forest management and climate change scenarios. We projected change in habitat suitability across the boreal and boreo-nemoral regions of Sweden for the period 2020-2100. Scenarios varied in the proportion of forest set-aside from production, the level of timber extraction, and the magnitude of climate change. Habitat suitabilities for the study species were projected to show larger relative increases over time in the boreo-nemoral region compared to the boreal region, under all scenarios. By 2100, mean suitabilities in set-aside forest in the boreo-nemoral region were similar to the suitabilities projected for set-aside forest in the boreal region in 2020, suggesting that occurrence in the boreo-nemoral region could be increased. However, across all scenarios, consistently higher projected suitabilities in set-aside forest in the boreal region indicated that the boreal region remained the species stronghold. Furthermore, negative effects of climate change were evident in the boreal region, and projections suggested that climatic changes may eventually counteract the positive effects of forest management in the boreo-nemoral region. Our results suggest that the current rarity of this old-growth indicator species in the boreo-nemoral region may be due to the history of intensive

  9. Using Misperception to Counteract Noise in the Iterated Prisoner's Dilemma

    Science.gov (United States)

    Brumley, Lachlan; Korb, Kevin B.; Kopp, Carlo

    The Iterated Prisoner's Dilemma is a game-theoretical model which can be identified in many repeated real-world interactions between competing entities. The Tit for Tat strategy has been identified as a successful strategy which reinforces mutual cooperation, however, it is sensitive to environmental noise which disrupts continued cooperation between players to their detriment. This paper explores whether a population of Tit for Tat players may evolve specialised individual-based noise to counteract environmental noise. We have found that when the individual-based noise acts similarly to forgiveness it can counteract the environmental noise, although excessive forgiveness invites the evolution of exploitative individual-based noise, which is highly detrimental to the population when widespread.

  10. A concept of a space hazard counteraction system: Astronomical aspects

    Science.gov (United States)

    Shustov, B. M.; Rykhlova, L. V.; Kuleshov, Yu. P.; Dubov, Yu. N.; Elkin, K. S.; Veniaminov, S. S.; Borovin, G. K.; Molotov, I. E.; Naroenkov, S. A.; Barabanov, S. I.; Emel'yanenko, V. V.; Devyatkin, A. V.; Medvedev, Yu. D.; Shor, V. A.; Kholshevnikov, K. V.

    2013-07-01

    The basic science of astronomy and, primarily, its branch responsible for studying the Solar System, face the most important practical task posed by nature and the development of human civilization—to study space hazards and to seek methods of counteracting them. In pursuance of the joint Resolution of the Federal Space Agency (Roscosmos) and the RAS (Russian Academy of Sciences) Space Council of June 23, 2010, the RAS Institute of Astronomy in collaboration with other scientific and industrial organizations prepared a draft concept of the federal-level program targeted at creating a system of space hazard detection and counteraction. The main ideas and astronomical content of the concept are considered in this article.

  11. Ghrelin counteracts insulin-induced activation of vagal afferent neurons via growth hormone secretagogue receptor.

    Science.gov (United States)

    Iwasaki, Yusaku; Dezaki, Katsuya; Kumari, Parmila; Kakei, Masafumi; Yada, Toshihiko

    2015-08-01

    Vagal afferent nerves sense meal-related gastrointestinal and pancreatic hormones and convey their information to the brain, thereby regulating brain functions including feeding. We have recently demonstrated that postprandial insulin directly acts on the vagal afferent neurons. Plasma concentrations of orexigenic ghrelin and anorexigenic insulin show reciprocal dynamics before and after meals. The present study examined interactive effects of ghrelin and insulin on vagal afferent nerves. Cytosolic Ca(2+) concentration ([Ca(2+)]i) in isolated nodose ganglion (NG) neurons was measured to monitor their activity. Insulin at 10(-7)M increased [Ca(2+)]i in NG neurons, and the insulin-induced [Ca(2+)]i increase was inhibited by treatment with ghrelin at 10(-8)M. This inhibitory effect of ghrelin was attenuated by [D-Lys(3)]-GHRP-6, an antagonist of growth hormone-secretagogue receptor (GHSR). Des-acyl ghrelin had little effect on insulin-induced [Ca(2+)]i increases in NG neurons. Ghrelin did not affect [Ca(2+)]i increases in response to cholecystokinin (CCK), a hormone that inhibits feeding via vagal afferent neurons, indicating that ghrelin selectively counteracts the insulin action. These results demonstrate that ghrelin via GHSR suppresses insulin-induced activation of NG neurons. The action of ghrelin to counteract insulin effects on NG might serve to efficiently inform the brain of the systemic change between fasting-associated ghrelin-dominant and fed-associated insulin-dominant states for the homeostatic central regulation of feeding and metabolism.

  12. Spatial warping by oriented line detectors can counteract neural delays

    Directory of Open Access Journals (Sweden)

    Don eVaughn

    2013-11-01

    Full Text Available The slow speed of neural transmission necessitates that cortical visual information from dynamic scenes will lag reality. The perceiving the present (PTP hypothesis suggests that the visual system can mitigate the effect of such delays by spatially warping scenes to look as they will in ~100 ms from now (Changizi, 2001. We here show that the Hering illusion, in which straight lines appear bowed, can be induced by a background of optic flow, consistent with the PTP hypothesis. However, importantly, the bowing direction is the same whether the flow is inward or outward. This suggests that if the warping is meant to counteract latencies, it is accomplished by a simple strategy that is insensitive to motion direction, and that works only under typical (forward-moving circumstances. We also find that the illusion strengthens with longer pulses of optic flow, demonstrating motion integration over ~80 ms. The illusion is identical whether optic flow precedes or follows the flashing of bars, exposing the spatial warping to be equally postdictive and predictive, i.e., peri-dictive. Additionally, the illusion is diminished by cues which suggest the bars are independent of the background movement. Collectively, our findings are consistent with a role for networks of visual orientation-tuned neurons (e.g., simple cells in primary visual cortex in spatial warping. We conclude that under the common condition of forward ego-motion, spatial warping counteracts the disadvantage of neural latencies. It is not possible to prove that this is the purpose of spatial warping, but our findings at minimum place constraints on the PTP hypothesis, demonstrating that any spatial warping for the purpose of counteracting neural delays is not a precise, on-the-fly computation, but instead a heuristic achieved by a simple mechanism that succeeds under normal circumstances.

  13. Counteractive effect of antacid suspensions on intrinsic dental erosion.

    Science.gov (United States)

    Turssi, Cecilia P; Vianna, Lídia M F F; Hara, Anderson T; do Amaral, Flávia L B; França, Fabiana M G; Basting, Roberta T

    2012-08-01

    This in vitro study aimed to investigate the anti-erosive effect of antacid suspensions applied to enamel after exposure to hydrochloric acid (HCl). Ninety bovine enamel slabs were embedded, flattened, and polished. Reference areas were created and specimens were divided into six groups. They were exposed to 0.01 M HCl (pH 2) for 2 min, followed by immersion for 1 min in one of the following test suspensions: magnesium hydroxide, aluminum hydroxide, magnesium hydroxide/aluminum hydroxide, sodium alginate/sodium bicarbonate/calcium carbonate, or hydrated magnesium aluminate. Artificial saliva was used as a negative control. Specimens were subjected to a total of five cycles of erosion/antacid treatment. Enamel surface loss was measured (in micrometers) by optical profilometry. In addition, baseline and final surface microhardness (SMH) values of enamel were obtained. It was found that antacid suspensions significantly reduced enamel loss, and that similar protection was afforded by all formulations. No differences were observed between the final enamel SMH values among groups. Antacid suspensions counteracted HCl-induced enamel loss, although they were not effective in reducing enamel softening. Mouth rinsing with antacid suspensions after vomiting can potentially represent a promising strategy to counteract enamel loss caused by erosion.

  14. Robo 4 Counteracts Angiogenesis in Herpetic Stromal Keratitis.

    Directory of Open Access Journals (Sweden)

    Fernanda Gimenez

    Full Text Available The cornea is a complex tissue that must preserve its transparency to maintain optimal vision. However, in some circumstances, damage to the eye can result in neovascularization that impairs vision. This outcome can occur when herpes simplex virus type 1 (HSV-1 causes the immunoinflammatory lesion stromal keratitis (SK. Potentially useful measures to control the severity of SK are to target angiogenesis which with herpetic SK invariably involves VEGF. One such way to control angiogenesis involves the endothelial receptor Robo4 (R4, which upon interaction with another protein activates an antiangiogenic pathway that counteracts VEGF downstream signaling. In this study we show that mice unable to produce R4 because of gene knockout developed significantly higher angiogenesis after HSV-1 ocular infection than did infected wild type (WT controls. Moreover, providing additional soluble R4 (sR4 protein by subconjunctival administration to R4 KO HSV-1 infected mice substantially rescued the WT phenotype. Finally, administration of sR4 to WT HSV-1 infected mice diminished the extent of corneal angiogenesis compared to WT control animals. Our results indicate that sR4 could represent a useful therapeutic tool to counteract corneal angiogenesis and help control the severity of SK.

  15. 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

  16. 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.

  17. 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.

  18. Counteracting age-related loss of skeletal muscle mass

    DEFF Research Database (Denmark)

    Bechshøft, Rasmus; Reitelseder, Søren; Højfeldt, Grith;

    2016-01-01

    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...... to training, thereby attenuating the overall benefits of training. We hypothesize that light load resistance training is more efficient when both adherence and physical improvement are considered longitudinally. We launched the interdisciplinary project on Counteracting Age-related Loss of Skeletal Muscle....... Moreover, we will evaluate changes in physical performance, muscle fiber type and acute anabolic response to whey protein ingestion, sensory adaptation, gut microbiome, and a range of other measures, combined with questionnaires on life quality and qualitative interviews with selected subjects. The CALM...

  19. Plant-Derived Agents for Counteracting Cisplatin-Induced Nephrotoxicity

    Science.gov (United States)

    Venkataraman, Balaji; Kurdi, Amani; Mahgoub, Eglal; Sadek, Bassem

    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 the literature reveal partial amelioration of CSP-induced renal toxicity, stressing the need to develop potent combinatorial/synergistic agents for the mitigation of renal toxicity. However, the ideal renoprotective adjuvant should not interfere with the anticancer efficacy of CSP. In this review, we have discussed the progress made in utilizing plant-derived agents (phytochemicals) to combat CSP-induced nephrotoxicity in preclinical studies. Furthermore, we have also presented strategies to utilize phytochemicals as prototypes for the development of novel renoprotective agents for counteracting chemotherapy-induced renal damage.

  20. Voluntary exercise counteracts Aβ25-35-induced memory impairment in mice.

    Science.gov (United States)

    Wang, Qin; Xu, Zhiqiang; Tang, Jinrong; Sun, Jianguo; Gao, Junying; Wu, Ting; Xiao, Ming

    2013-11-01

    Exercise has been shown to enhance hippocampus-related cognition and slow the progression of Alzheimer's disease (AD). However, whether voluntary exercise directly decreases the neurotoxicity of amyloid peptide (Aβ) needs to be determined. In the present study, two-month old male C57bl/6 mice were intracerebroventricularly injected with Aβ25-35, and then allowed for voluntary exercise for 12 days. Y-maze test revealed that voluntary exercise mitigated spatial memory impairment induced by Aβ25-35. Consistently, Aβ25-35 treated mice with exercise showed reduced neuronal degeneration and synaptic protein loss in the hippocampus compared with sedentary controls. Moreover, voluntary exercise significantly ameliorated oxidative stress markers and increased vessel branches in the hippocampus of Aβ25-35 treated mice. Our results suggest that voluntary exercise counteracts the neurotoxicity of Aβ by reducing oxidative stress and increasing angiogenesis, which may underlie the beneficial effect of exercise on AD.

  1. 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

  2. In-vivo experimental demonstration that hyperhistaminism counteracts tumor-growth.

    Science.gov (United States)

    Dellarovere, F; Broccio, G; Granata, A; Fimiani, V

    1994-01-01

    Induction of hyperhistaminism in peritoneum of rats by daily intraperitoneal supply of 0.005 mu g of histamine, counteracts the growth of 10(3) Yoshida ascite sarcoma cells only if administration precedes inoculation of tumor cells and has a long duration. Treating animals for two weeks before tumor cell inoculation we observed significant 70% survival, that was increased to 80% continuing the supply for 20-days after the inoculation; treatment for 3 days before or 20 days after the inoculation did not show significant results. The condition created in rat peritoneum is similar to that in allergic people, and our data in animals confirm statistical data observed in allergic people showing decreased incidence of neoplastic disease due to histamine, that appears to be integrated in a highly potent immunoregulatory circuit.

  3. Sorbitol production in the lens: a means of counteracting glucose-derived osmotic stress.

    Science.gov (United States)

    Chylack, L T; Tung, W; Harding, R

    1986-01-01

    Heretofore, the intracellular accumulation of sorbitol has been associated exclusively with deleterious (cataractogenic) changes in the lens. This study demonstrates a beneficial role for the sorbitol pathway in the rabbit lens, namely that of counteracting extracellular, glucose-derived, osmotic stress with the intracellular production of osmotically active sorbitol. Large and sudden increases in the extracellular glucose concentration lead to dehydration of the lens, a response that can be diminished by intracellular sorbitol and fructose production. These results are discussed in light of the impact (beneficial/detrimental) of aldose reductase inhibitors on the lens. Sugar cataract formation appears to result from continuous, rather than cyclical, activity of a pathway which normally may have a protective function in the lens.

  4. Influence of Mn and Fe Counteraction on Rice (Oryza Sativa L.) Oranging Physiological Disease

    Institute of Scientific and Technical Information of China (English)

    LIAOZHONG-WEN; LINDONG-JIAO; 等

    1994-01-01

    Mn and Fe are two important micronutrients of paddy soils derived from red earths.Rice(Oryza sativa L.)oranging physiological diease in newly reclaimed red rarths is related to Fe toxicity.There have been considerable studies on Mn and Fe counteraction,but influence of Mn and Fe counteration on rice oranging physiological disease still remains unknown.This paper is to study,using two soils from USA and China respectively,the relationship between Nn and Fe counteraction and the physiological disease.Analysis for water soluble and extractable Fe and Mn showed that Mn/Fe ratios of the red earths were lower than those of the paddy soils.Fertilizing with Mn raised Mn/Fe and reduced oranging leaves,improved growth and increased yields.Analysis with electron probe showed that Mn treatment had less Fe deposit in root epidermis and more Ca and Si in roots.The results indicated that fertilizing with Mn could correct Fe toxicity.How to apply Mn and Fe counteraction in practice is worth further studying.

  5. DMPD: An arms race: innate antiviral responses and counteracting viral strategies. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18031256 An arms race: innate antiviral responses and counteracting viral strategie...s. Schroder M, Bowie AG. Biochem Soc Trans. 2007 Dec;35(Pt 6):1512-4. (.png) (.svg) (.html) (.csml) Show An arms race...: innate antiviral responses and counteracting viral strategies. PubmedID 18031256 Title An arms race

  6. 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.

  7. Plant-Derived Agents for Counteracting Cisplatin-Induced Nephrotoxicity

    Directory of Open Access Journals (Sweden)

    Shreesh Ojha

    2016-01-01

    Full Text Available 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 the literature reveal partial amelioration of CSP-induced renal toxicity, stressing the need to develop potent combinatorial/synergistic agents for the mitigation of renal toxicity. However, the ideal renoprotective adjuvant should not interfere with the anticancer efficacy of CSP. In this review, we have discussed the progress made in utilizing plant-derived agents (phytochemicals to combat CSP-induced nephrotoxicity in preclinical studies. Furthermore, we have also presented strategies to utilize phytochemicals as prototypes for the development of novel renoprotective agents for counteracting chemotherapy-induced renal damage.

  8. Molecular chaperones as therapeutic targets to counteract proteostasis defects.

    Science.gov (United States)

    Cattaneo, Monica; Dominici, Roberto; Cardano, Marina; Diaferia, Giuseppe; Rovida, Ermanna; Biunno, Ida

    2012-03-01

    The health of cells is preserved by the levels and correct folding states of the proteome, which is generated and maintained by the proteostasis network, an integrated biological system consisting of several cytoprotective and degradative pathways. Indeed, the health conditions of the proteostasis network is a fundamental prerequisite to life as the inability to cope with the mismanagement of protein folding arising from genetic, epigenetic, and micro-environment stress appears to trigger a whole spectrum of unrelated diseases. Here we describe the potential functional role of the proteostasis network in tumor biology and in conformational diseases debating on how the signaling branches of this biological system may be manipulated to develop more efficacious and selective therapeutic strategies. We discuss the dual strategy of these processes in modulating the folding activity of molecular chaperones in order to counteract the antithetic proteostasis deficiencies occurring in cancer and loss/gain of function diseases. Finally, we provide perspectives on how to improve the outcome of these disorders by taking advantage of proteostasis modeling.

  9. 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.

  10. Sweet delusion. Glucose drinks fail to counteract ego depletion.

    Science.gov (United States)

    Lange, Florian; Eggert, Frank

    2014-04-01

    Initial acts of self-control have repeatedly been shown to reduce individuals' performance on a consecutive self-control task. In addition, sugar containing drinks have been demonstrated to counteract this so-called ego-depletion effect, both when being ingested and when merely being sensed in the oral cavity. However, since the underlying evidence is less compelling than suggested, replications are crucially required. In Experiment 1, 70 participants consumed a drink containing either sugar or a non-caloric sweetener between two administrations of delay-discounting tasks. Experiment 2 (N=115) was designed to unravel the psychological function of oral glucose sensing by manipulating the temporal delay between a glucose mouth rinse and the administration of the consecutive self-control task. Despite applying powerful research designs, no effect of sugar sensing or ingestion on ego depletion could be detected. These findings add to previous challenges of the glucose model of self-control and highlight the need for independent replications.

  11. Targeting species D adenoviruses replication to counteract the epidemic keratoconjunctivitis.

    Science.gov (United States)

    Nikitenko, Natalia A; Speiseder, Thomas; Groitl, Peter; Spirin, Pavel V; Prokofjeva, Maria M; Lebedev, Timofey D; Rubtsov, Petr M; Lam, Elena; Riecken, Kristoffer; Fehse, Boris; Dobner, Thomas; Prassolov, Vladimir S

    2015-06-01

    Human adenoviruses are non-enveloped DNA viruses causing various infections; their pathogenicity varies dependent on virus species and type. Although acute infections can sometimes take severe courses, they are rarely fatal in immune-competent individuals. Adenoviral conjunctivitis and epidemic keratoconjunctivitis are hyperacute and highly contagious infections of the eye caused by human adenovirus types within species D. Currently there is no causal treatment available to counteract these diseases effectively. The E2B region of the adenovirus genome encodes for the viral DNA polymerase, which is required for adenoviral DNA replication. Here we propose novel model systems to test this viral key factor, DNA polymerase, as a putative target for the development of efficient antiviral therapy based on RNA interference. Using our model cell lines we found that different small interfering RNAs mediate significant suppression (up to 90%) of expression levels of viral DNA polymerase upon transfection. Moreover, permanent expression of short hairpin RNA based on the most effective small interfering RNA led to a highly significant, more than tenfold reduction in replication for different human group D adenoviruses involved in ocular infections.

  12. Postactivation potentiation can counteract declines in force and power that occur after stretching.

    Science.gov (United States)

    Kümmel, J; Kramer, A; Cronin, N J; Gruber, M

    2016-12-09

    Stretching can decrease a muscle's maximal force, whereas short but intense muscle contractions can increase it. We hypothesized that when combined, postactivation potentiation induced by reactive jumps would counteract stretch-induced decrements in drop jump (DJ) performance. Moreover, we measured changes in muscle twitch forces and ankle joint stiffness (KAnkle ) to examine underlying mechanisms. Twenty subjects completed three DJs and 10 electrically evoked muscle twitches of the triceps surae subsequent to four different conditioning activities and control. The conditioning activities were 10 hops, 20s of static stretching of the triceps surae muscle, 20s of stretching followed by 10 hops, and vice versa. After 10 hops, twitch peak torque (TPT) was 20% and jump height 5% higher compared with control with no differences in KAnkle . After stretching, TPT and jump height were both 9% and KAnkle 6% lower. When hops and stretching were combined as conditioning activities, jump height was not different compared with control but significantly higher (11% and 8%) compared with stretching. TPTs were 16% higher compared with control when the hops were performed after stretching and 9% higher compared with the reverse order. KAnkle was significantly lower when stretching was performed after the hops (6%) compared with control, but no significant difference was observed when hops were performed after stretching. These results demonstrate that conditioning hops can counteract stretch-related declines in DJ performance. Furthermore, the differences in TPTs and KAnkle between combined conditioning protocols indicate that the order of conditioning tasks might play an important role at the muscle-tendon level. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. 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.

  14. Antihypertensive efficacy of angiotensin converting enzyme inhibition and aspirin counteraction.

    Science.gov (United States)

    Guazzi, M D; Campodonico, J; Celeste, F; Guazzi, M; Santambrogio, G; Rossi, M; Trabattoni, D; Alimento, M

    1998-01-01

    Blockade of bradykinin breakdown and enhancement of prostaglandin release probably participate in the antihypertensive activity of angiotensin converting enzyme (ACE) inhibitors. Cyclooxygenase blockers may attenuate the efficacy of ACE inhibitors by interfering with prostaglandin synthesis, and patients taking aspirin may not benefit from ACE inhibition. This study was designed to evaluate the incidence of the counteractive phenomenon and to define minimal aspirin dosage that causes an antagonistic effect. These were 26 patients with mild to moderate hypertension (group 1) and 26 patients with severe untreated primary hypertension (group 2). Enalapril (20 mg twice a day) was used as a single drug in group 1 and was added to the combination of long-acting nifedipine (30 mg/day) and atenolol (50 mg/day) in group 2. Aspirin was tested at doses of 100 and 300 mg/day, and an attenuation of more than 20% of the mean blood pressure decrease produced by enalapril was the criteria that defined antagonism. The 100 mg dose was ineffective. However, 300 mg aspirin had an antagonistic effect in 57% of patients in group 1 and 50% of patients in group 2: mean arterial pressure was lowered by 63% and 91% less, respectively. Results were independent of the drug administration order. In "responders," aspirin significantly attenuated the renin rise associated with ACE inhibition. These findings suggest that a number of ACE-inhibited patients are susceptible to 300 mg/day aspirin, regardless of hypertension severity. Antagonism may be mediated through prostaglandin inhibition according to predominance, in an individual patient, of prostaglandin activation (also as a renin secretory stimulus) or angiotensin blockade by enalapril.

  15. RIPK1 counteracts ZBP1-mediated necroptosis to inhibit inflammation.

    Science.gov (United States)

    Lin, Juan; Kumari, Snehlata; Kim, Chun; Van, Trieu-My; Wachsmuth, Laurens; Polykratis, Apostolos; Pasparakis, Manolis

    2016-12-01

    Receptor-interacting protein kinase 1 (RIPK1) regulates cell death and inflammation through kinase-dependent and -independent functions. RIPK1 kinase activity induces caspase-8-dependent apoptosis and RIPK3 and mixed lineage kinase like (MLKL)-dependent necroptosis. In addition, RIPK1 inhibits apoptosis and necroptosis through kinase-independent functions, which are important for late embryonic development and the prevention of inflammation in epithelial barriers. The mechanism by which RIPK1 counteracts RIPK3-MLKL-mediated necroptosis has remained unknown. Here we show that RIPK1 prevents skin inflammation by inhibiting activation of RIPK3-MLKL-dependent necroptosis mediated by Z-DNA binding protein 1 (ZBP1, also known as DAI or DLM1). ZBP1 deficiency inhibited keratinocyte necroptosis and skin inflammation in mice with epidermis-specific RIPK1 knockout. Moreover, mutation of the conserved RIP homotypic interaction motif (RHIM) of endogenous mouse RIPK1 (RIPK1(mRHIM)) caused perinatal lethality that was prevented by RIPK3, MLKL or ZBP1 deficiency. Furthermore, mice expressing only RIPK1(mRHIM) in keratinocytes developed skin inflammation that was abrogated by MLKL or ZBP1 deficiency. Mechanistically, ZBP1 interacted strongly with phosphorylated RIPK3 in cells expressing RIPK1(mRHIM), suggesting that the RIPK1 RHIM prevents ZBP1 from binding and activating RIPK3. Collectively, these results show that RIPK1 prevents perinatal death as well as skin inflammation in adult mice by inhibiting ZBP1-induced necroptosis. Furthermore, these findings identify ZBP1 as a critical mediator of inflammation beyond its previously known role in antiviral defence and suggest that ZBP1 might be implicated in the pathogenesis of necroptosis-associated inflammatory diseases.

  16. Non-endothelial endothelin counteracts hypoxic vasodilation in porcine large coronary arteries

    Directory of Open Access Journals (Sweden)

    Fröbert Ole

    2011-05-01

    Full Text Available Abstract Background The systemic vascular response to hypoxia is vasodilation. However, reports suggest that the potent vasoconstrictor endothelin-1 (ET-1 is released from the vasculature during hypoxia. ET-1 is reported to augment superoxide anion generation and may counteract nitric oxide (NO vasodilation. Moreover, ET-1 was proposed to contribute to increased vascular resistance in heart failure by increasing the production of asymmetric dimethylarginine (ADMA. We investigated the role of ET-1, the NO pathway, the potassium channels and radical oxygen species in hypoxia-induced vasodilation of large coronary arteries. Results In prostaglandin F2α (PGF2α, 10 μM-contracted segments with endothelium, gradual lowering of oxygen tension from 95 to 1% O2 resulted in vasodilation. The vasodilation to O2 lowering was rightward shifted in segments without endothelium at all O2 concentrations except at 1% O2. The endothelin receptor antagonist SB217242 (10 μM markedly increased hypoxic dilation despite the free tissue ET-1 concentration in the arterial wall was unchanged in 1% O2 versus 95% O2. Exogenous ET-1 reversed hypoxic dilation in segments with and without endothelium, and the hypoxic arteries showed an increased sensitivity towards ET-1 compared to the normoxic controls. Without affecting basal NO, hypoxia increased NO concentration in PGF2α-contracted arteries, and an NO synthase inhibitor, L-NOARG,(300 μM, NG-nitro-L-Arginine reduced hypoxic vasodilation. NO-induced vasodilation was reduced in endothelin-contracted preparations. Arterial wall ADMA concentrations were unchanged by hypoxia. Blocking of potassium channels with TEA (tetraethylammounium chloride(10 μM inhibited vasodilation to O2 lowering as well as to NO. The superoxide scavenger tiron (10 μM and the putative NADPH oxidase inhibitor apocynin (10 μM leftward shifted concentration-response curves for O2 lowering without changing vasodilation to 1% O2. PEG (polyethylene

  17. Stimulation of NTS A1 adenosine receptors evokes counteracting effects on hindlimb vasculature.

    Science.gov (United States)

    McClure, Joseph M; O'Leary, Donal S; Scislo, Tadeusz J

    2005-12-01

    Our previous studies concluded that stimulation of the nucleus of the solitary tract (NTS) A2a receptors evokes preferential hindlimb vasodilation mainly via inducing increases in preganglionic sympathetic nerve activity (pre-ASNA) directed to the adrenal medulla. This increase in pre-ASNA causes the release of epinephrine and subsequent activation of beta-adrenergic receptors that are preferentially located in the skeletal muscle vasculature. Selective activation of NTS A1 adenosine receptors evokes variable, mostly pressor effects and increases pre-ASNA, as well as lumbar sympathetic activity, which is directed to the hindlimb. These counteracting factors may have opposite effects on the hindlimb vasculature resulting in mixed vascular responses. Therefore, in chloralose-urethane-anesthetized rats, we evaluated the contribution of vasodilator versus vasoconstrictor effects of stimulation of NTS A1 receptors on the hindlimb vasculature. We compared the changes in iliac vascular conductance evoked by microinejctions into the NTS of the selective A1 receptor agonist N6-cyclopentyladenosine (330 pmol in 50 nl volume) in intact animals with the responses evoked after beta-adrenergic blockade, bilateral adrenalectomy, bilateral lumbar sympathectomy, and combined adrenalectomy + lumbar sympathectomy. In intact animals, stimulation of NTS A1 receptors evoked variable effects: increases and decreases in mean arterial pressure and iliac conductance with prevailing pressor and vasoconstrictor effects. Peripheral beta-adrenergic receptor blockade and bilateral adrenalectomy eliminated the depressor component of the responses, markedly potentiated iliac vasoconstriction, and tended to increase the pressor responses. Lumbar sympathectomy tended to decrease the pressor and vasoconstrictor responses. After bilateral adrenalectomy plus lumbar sympathectomy, a marked vasoconstriction in iliac vascular bed still persisted, suggesting that the vasoconstrictor component of the

  18. Definition of singularity due to Newton’s second law counteracting gravity

    National Research Council Canada - National Science Library

    Arezu Jahanshir; Hossein Javadi; Farshid forouzbakhsh

    2013-01-01

    .... Regarding on review of Newton's second law in this paper, we have been attempted toenter to the sub-quantum space by crossing the border of quantum mechanics thento survey of counteracting Newton's...

  19. Celecoxib-induced gastrointestinal, liver and brain lesions in rats, counteraction by BPC 157 or L-arginine, aggravation by L-NAME.

    Science.gov (United States)

    Drmic, Domagoj; Kolenc, Danijela; Ilic, Spomenko; Bauk, Lara; Sever, Marko; Zenko Sever, Anita; Luetic, Kresimir; Suran, Jelena; Seiwerth, Sven; Sikiric, Predrag

    2017-08-07

    To counteract/reveal celecoxib-induced toxicity and NO system involvement. Celecoxib (1 g/kg b.w. ip) was combined with therapy with stable gastric pentadecapeptide BPC 157 (known to inhibit these lesions, 10 μg/kg, 10 ng/kg, or 1 ng/kg ip) and L-arginine (100 mg/kg ip), as well as NOS blockade [N(G)-nitro-L-arginine methyl ester (L-NAME)] (5 mg/kg ip) given alone and/or combined immediately after celecoxib. Gastrointestinal, liver, and brain lesions and liver enzyme serum values in rats were assessed at 24 h and 48 h thereafter. This high-dose celecoxib administration, as a result of NO system dysfunction, led to gastric, liver, and brain lesions and increased liver enzyme serum values. The L-NAME-induced aggravation of the lesions was notable for gastric lesions, while in liver and brain lesions the beneficial effect of L-arginine was blunted. L-arginine counteracted gastric, liver and brain lesions. These findings support the NO system mechanism(s), both NO system agonization (L-arginine) and NO system antagonization (L-NAME), that on the whole are behind all of these COX phenomena. An even more complete antagonization was identified with BPC 157 (at both 24 h and 48 h). A beneficial effect was evident on all the increasingly negative effects of celecoxib and L-NAME application and in all the BPC 157 groups (L-arginine + BPC 157; L-NAME + BPC 157; L-NAME + L-arginine + BPC 157). Thus, these findings demonstrated that BPC 157 may equally counteract both COX-2 inhibition (counteracting the noxious effects of celecoxib on all lesions) and additional NOS blockade (equally counteracting the noxious effects of celecoxib + L-NAME). BPC 157 and L-arginine alleviate gastrointestinal, liver and brain lesions, redressing NSAIDs' post-surgery application and NO system involvement.

  20. Salt Potentiates Methylamine Counteraction System to Offset the Deleterious Effects of Urea on Protein Stability and Function

    Science.gov (United States)

    Singh, Laishram R.; Warepam, Marina; Ahmad, Faizan; Dar, Tanveer Ali

    2015-01-01

    Cellular methylamines are osmolytes (low molecular weight organic compounds) believed to offset the urea’s harmful effects on the stability and function of proteins in mammalian kidney and marine invertebrates. Although urea and methylamines are found at 2:1 molar ratio in tissues, their opposing effects on protein structure and function have been questioned on several grounds including failure to counteraction or partial counteraction. Here we investigated the possible involvement of cellular salt, NaCl, in urea-methylamine counteraction on protein stability and function. We found that NaCl mediates methylamine counteracting system from no or partial counteraction to complete counteraction of urea’s effect on protein stability and function. These conclusions were drawn from the systematic thermodynamic stability and functional activity measurements of lysozyme and RNase-A. Our results revealed that salts might be involved in protein interaction with charged osmolytes and hence in the urea-methylamine counteraction. PMID:25793733

  1. Salt potentiates methylamine counteraction system to offset the deleterious effects of urea on protein stability and function.

    Directory of Open Access Journals (Sweden)

    Safikur Rahman

    Full Text Available Cellular methylamines are osmolytes (low molecular weight organic compounds believed to offset the urea's harmful effects on the stability and function of proteins in mammalian kidney and marine invertebrates. Although urea and methylamines are found at 2:1 molar ratio in tissues, their opposing effects on protein structure and function have been questioned on several grounds including failure to counteraction or partial counteraction. Here we investigated the possible involvement of cellular salt, NaCl, in urea-methylamine counteraction on protein stability and function. We found that NaCl mediates methylamine counteracting system from no or partial counteraction to complete counteraction of urea's effect on protein stability and function. These conclusions were drawn from the systematic thermodynamic stability and functional activity measurements of lysozyme and RNase-A. Our results revealed that salts might be involved in protein interaction with charged osmolytes and hence in the urea-methylamine counteraction.

  2. Oxidation-induced loss of the ability of HDL to counteract the inhibitory effect of oxidized LDL on vasorelaxation.

    Science.gov (United States)

    Perségol, Laurence; Brindisi, Marie-Claude; Rageot, David; Pais de Barros, Jean-Paul; Monier, Serge; Vergès, Bruno; Duvillard, Laurence

    2015-11-01

    Several current diseases are associated with an increase in the oxidation of HDL, which is likely to impair their functionality. Our aim was to identify whether oxidation could change the protective effect of HDL against the deleterious effect on vasoreactivity induced by oxidative stress. HDL from healthy subjects were oxidized in vitro by Cu(2+), and the ability of oxidized HDL to counteract the inhibitory effect of oxidized LDL on acetylcholine-induced vasodilation was tested on isolated rabbit aorta rings. Oxidation of HDL was evidenced by the increase in the 7-oxysterols/cholesterol ratio (3.20 ± 1.12 vs 0.02 ± 0.01 % in native HDL, p HDL counteracted this inhibition (E max = 72.4 ± 4.8 vs 50.2 ± 5.0 % p HDL had no effect on oxidized LDL-induced inhibition on endothelium-dependent vasorelaxation (E max = 53.7 ± 4.8 vs 50.2 ± 5.0 %, NS). HDL oxidation is associated with a decreased ability of HDL to remove 7-oxysterols from oxidized LDL. In conclusion, these results show that oxidation of HDL induces the loss of their protective effect against endothelial dysfunction, which could promote atherosclerosis in diseases associated with increased oxidative stress.

  3. Cyclophilin D, a target for counteracting skeletal muscle dysfunction in mitochondrial myopathy.

    Science.gov (United States)

    Gineste, Charlotte; Hernandez, Andres; Ivarsson, Niklas; Cheng, Arthur J; Naess, Karin; Wibom, Rolf; Lesko, Nicole; Bruhn, Helene; Wedell, Anna; Freyer, Christoph; Zhang, Shi-Jin; Carlström, Mattias; Lanner, Johanna T; Andersson, Daniel C; Bruton, Joseph D; Wredenberg, Anna; Westerblad, Håkan

    2015-12-01

    Muscle weakness and exercise intolerance are hallmark symptoms in mitochondrial disorders. Little is known about the mechanisms leading to impaired skeletal muscle function and ultimately muscle weakness in these patients. In a mouse model of lethal mitochondrial myopathy, the muscle-specific Tfam knock-out (KO) mouse, we previously demonstrated an excessive mitochondrial Ca(2+) uptake in isolated muscle fibers that could be inhibited by the cyclophilin D (CypD) inhibitor, cyclosporine A (CsA). Here we show that the Tfam KO mice have increased CypD levels, and we demonstrate that this increase is a common feature in patients with mitochondrial myopathy. We tested the effect of CsA treatment on Tfam KO mice during the transition from a mild to terminal myopathy. CsA treatment counteracted the development of muscle weakness and improved muscle fiber Ca(2+) handling. Importantly, CsA treatment prolonged the lifespan of these muscle-specific Tfam KO mice. These results demonstrate that CsA treatment is an efficient therapeutic strategy to slow the development of severe mitochondrial myopathy.

  4. Resveratrol counteracts lipopolysaccharide-induced depressive-like behaviors via enhanced hippocampal neurogenesis

    Science.gov (United States)

    Liu, Liang; Zhang, Qin; Cai, Yulong; Sun, Dayu; He, Xie; Wang, Lian; Yu, Dan; Li, Xin; Xiong, Xiaoyi; Xu, Haiwei; Yang, Qingwu; Fan, Xiaotang

    2016-01-01

    Radial glial-like cells (RGLs) in the adult dentate gyrus (DG) function as progenitor cells for adult hippocampal neurogenesis, a process involved in the stress-related pathophysiology and treatment efficiency of depression. Resveratrol (RSV) has been demonstrated to be a potent activator of neurogenesis. The present study investigated whether chronic RSV treatment has antidepressant potential in relation to hippocampal neurogenesis. Mice received two weeks of RSV (20 mg/kg) or dimethylsulfoxide (DMSO) treatment, followed by lipopolysaccharide (LPS; 1 mg/kg) or saline injections for 5 days. We found that RSV treatment abrogated the increased immobility in the forced swimming test and tail suspension test induced by LPS. Immunohistochemical staining revealed that RSV treatment reversed the increase in microglial activation and the inhibition in DG neurogenesis. RSV treatment also attenuated LPS-induced defects in the expanding of RGLs through promoting symmetric division. In addition, RSV ameliorated LPS-induced NF-κB activation in the hippocampus coincides with the up-regulation levels of Sirt1 and Hes1. Taken together, these data indicated that RSV-induced Sirt1 activation counteracts LPS-induced depression-like behaviors via a neurogenic mechanism. A new model to understand the role of RSV in treating depression may result from these findings. PMID:27517628

  5. Limpets counteract ocean acidification induced shell corrosion by thickening of aragonitic shell layers

    Directory of Open Access Journals (Sweden)

    G. Langer

    2014-08-01

    Full Text Available Specimens of the patellogastropod limpet Patella caerulea were collected within (pHlow-shells and outside (pHn-shells a CO2 vent site at Ischia, Italy. Four pHlow-shells and four pHn-shells were sectioned transversally and scanned for polymorph distribution by means of confocal Raman microscopy. The pHlow-shells displayed a twofold increase in aragonite area fraction and size normalised aragonite area. Size normalised calcite area was halved in pHlow-shells. Taken together with the increased apical and the decreased flank size normalised thickness of the pHlow-shells, these data led us to conclude that low pH exposed P. caerulea specimens counteract shell dissolution by enhanced shell production. The latter is different from normal elongation growth and proceeds through addition of aragonitic layers only, while the production of calcitic layers is confined to elongation growth. Therefore aragonite cannot be regarded as a per se disadvantageous polymorph under ocean acidification conditions.

  6. Limpets counteract ocean acidification induced shell corrosion by thickening of aragonitic shell layers

    Science.gov (United States)

    Langer, G.; Nehrke, G.; Baggini, C.; Rodolfo-Metalpa, R.; Hall-Spencer, J. M.; Bijma, J.

    2014-12-01

    Specimens of the patellogastropod limpet Patella caerulea were collected within (pHlow-shells) and outside (pHn-shells) a CO2 vent site at Ischia, Italy. Four pHlow-shells and four pHn-shells were sectioned transversally and scanned for polymorph distribution by means of confocal Raman microscopy. The pHlow-shells displayed a twofold increase in aragonite area fraction and size-normalised aragonite area. Size-normalised calcite area was halved in pHlow-shells. Taken together with the increased apical and the decreased flank size-normalised thickness of the pHlow-shells, these data led us to conclude that low-pH-exposed P. caerulea specimens counteract shell dissolution by enhanced shell production. This is different from normal elongation growth and proceeds through addition of aragonitic parts only, while the production of calcitic parts is confined to elongation growth. Therefore, aragonite cannot be regarded as a disadvantageous polymorph per se under ocean acidification conditions.

  7. VEGF receptor-2 (Flk-1 overexpression in mice counteracts focal epileptic seizures.

    Directory of Open Access Journals (Sweden)

    Litsa Nikitidou

    Full Text Available Vascular endothelial growth factor (VEGF was first described as an angiogenic agent, but has recently also been shown to exert various neurotrophic and neuroprotective effects in the nervous system. These effects of VEGF are mainly mediated by its receptor, VEGFR-2, which is also referred to as the fetal liver kinase receptor 1 (Flk-1. VEGF is up-regulated in neurons and glial cells after epileptic seizures and counteracts seizure-induced neurodegeneration. In vitro, VEGF administration suppresses ictal and interictal epileptiform activity caused by AP4 and 0 Mg(2+ via Flk-1 receptor. We therefore explored whether increased VEGF signaling through Flk-1 overexpression may regulate epileptogenesis and ictogenesis in vivo. To this extent, we used transgenic mice overexpressing Flk-1 postnatally in neurons. Intriguingly, Flk-1 overexpressing mice were characterized by an elevated threshold for seizure induction and a decreased duration of focal afterdischarges, indicating anti-ictal action. On the other hand, the kindling progression in these mice was similar to wild-type controls. No significant effects on blood vessels or glia cells, as assessed by Glut1 and GFAP immunohistochemistry, were detected. These results suggest that increased VEGF signaling via overexpression of Flk-1 receptors may directly affect seizure activity even without altering angiogenesis. Thus, Flk-1 could be considered as a novel target for developing future gene therapy strategies against ictal epileptic activity.

  8. Interleukin-35 administration counteracts established murine type 1 diabetes--possible involvement of regulatory T cells.

    Science.gov (United States)

    Singh, Kailash; Kadesjö, Erik; Lindroos, Julia; Hjort, Marcus; Lundberg, Marcus; Espes, Daniel; Carlsson, Per-Ola; Sandler, Stellan; Thorvaldson, Lina

    2015-07-30

    The anti-inflammatory cytokine IL-35 is produced by regulatory T (Treg) cells to suppress autoimmune and inflammatory responses. The role of IL-35 in type 1 diabetes (T1D) remains to be answered. To elucidate this, we investigated the kinetics of Treg cell response in the multiple low dose streptozotocin induced (MLDSTZ) T1D model and measured the levels of IL-35 in human T1D patients. We found that Treg cells were increased in MLDSTZ mice. However, the Treg cells showed a decreased production of anti-inflammatory (IL-10, IL-35, TGF-β) and increased pro-inflammatory (IFN-γ, IL-2, IL-17) cytokines, indicating a phenotypic shift of Treg cells under T1D condition. IL-35 administration effectively both prevented development of, and counteracted established MLDSTZ T1D, seemingly by induction of Eos expression and IL-35 production in Treg cells, thus reversing the phenotypic shift of the Treg cells. IL-35 administration reversed established hyperglycemia in NOD mouse model of T1D. Moreover, circulating IL-35 levels were decreased in human T1D patients compared to healthy controls. These findings suggest that insufficient IL-35 levels play a pivotal role in the development of T1D and that treatment with IL-35 should be investigated in treatment of T1D and other autoimmune diseases.

  9. 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.

  10. Probiotics to counteract biofilm-associated infections:promising and conflicting data

    Institute of Scientific and Technical Information of China (English)

    Claudia Vuotto; Francesca Longo; Gianfranco Donelli

    2014-01-01

    Altered bowel flora is currently thought to play a role in a variety of disease conditions, and the use of Bifidobacterium spp. and Lactobacillus spp. as probiotics has been demonstrated to be health-promoting, even if the success of their administration depends on the applied bacterial strain(s) and the targeted disease. In the last few decades, specific probiotics have been shown to be effective in the treatment or the prevention of acute viral gastroenteritis, pediatric post-antibiotic-associated diarrhea, some pediatric allergic disorders, necrotizing enterocolitis in preterm infants, inflammatory bowel diseases and postsurgical pouchitis. The potential application of probiotics is continuously widening, with new evidence accumulating to support their effect on the prevention and treatment of other disease conditions, including several oral diseases, such as dental caries, periodontal diseases and oral malodor, as well as genitourinary and wound infections. Considering the increasingly widespread ability of pathogens to generate persistent biofilm-related infections, an even more attractive proposal is to administer probiotics to prevent or counteract biofilm development. The response of biofilm-based oral, intestinal, vaginal and wound infections to probiotics treatment will be reviewed here in light of the most recent results obtained in this field.

  11. Discussing the undiscussable with the powerful: why and how faculty must learn to counteract organizational silence.

    Science.gov (United States)

    Dankoski, Mary E; Bickel, Janet; Gusic, Maryellen E

    2014-12-01

    Dialogue is essential for transforming institutions into learning organizations, yet many well-known characteristics of academic health centers (AHCs) interfere with open discussion. Rigid hierarchies, intense competition for resources, and the power of peer review in advancement processes all hamper difficult conversations, thereby contributing to organizational silence, and at great cost to the institution. Information necessary for critical decisions is not shared, individuals and the organization do not learn from mistakes, and diverse perspectives from those with less power are not entertained, or worse, are suppressed. When leaders become more skilled at inviting multiple perspectives and faculty more adept at broaching difficult conversations with those in power, differences are more effectively addressed and conflicts resolved. In this article, the authors frame why this skill is an essential competency for faculty and leaders alike and provide the following recommendations to institutions for increasing capacity in this area: (1) develop leaders to counteract organizational silence, (2) develop faculty members' skills in raising difficult issues with those in positions of power, and (3) train mentors to coach others in raising difficult conversations. The vitality of AHCs requires that faculty and institutional leaders develop relational communication skills and partner in learning through challenging conversations.

  12. Coumestrol Counteracts Interleukin-1β-Induced Catabolic Effects by Suppressing Inflammation in Primary Rat Chondrocytes.

    Science.gov (United States)

    You, Jae-Seek; Cho, In-A; Kang, Kyeong-Rok; Oh, Ji-Su; Yu, Sang-Joun; Lee, Gyeong-Je; Seo, Yo-Seob; Kim, Su-Gwan; Kim, Chun Sung; Kim, Do Kyung; Im, Hee-Jeong; Kim, Jae-Sung

    2017-02-01

    In the present study, we investigated the anti-catabolic effects of coumestrol, a phytoestrogen derived from herbal plants, against interleukin-1β-induced cartilage degeneration in primary rat chondrocytes and articular cartilage. Coumestrol did not affect the viability of human normal oral keratinocytes and primary rat chondrocytes treated for 24 h and 21 days, respectively. Although coumestrol did not significantly increase the proteoglycan contents in long-term culture, it abolished the interleukin-1β-induced loss of proteoglycans in primary rat chondrocytes and knee articular cartilage. Furthermore, coumestrol suppressed the expression of matrix-degrading enzymes such as matrix metalloproteinase-13, -3, and -1 in primary rat chondrocytes stimulated with interleukin-1β. Moreover, the expression of catabolic factors such as nitric oxide synthase, cyclooxygenase-2, prostaglandin E2, and inflammatory cytokines in interleukin-1β-stimulated primary rat chondrocytes was suppressed by coumestrol. In summary, these results indicate that coumestrol counteracts the catabolic effects induced by interleukin-1β through the suppression of inflammation. Therefore, based on its biological activity and safety profile, coumestrol could be used as a potential anti-catabolic biomaterial for osteoarthritis.

  13. URGENT DESTABILIZERS OF PUBLIC AND STATE SECURITY, TACTICS OF COUNTERACTION TO IT

    Directory of Open Access Journals (Sweden)

    D. N. Marinkin

    2016-01-01

    Full Text Available At creation of civil society in any constitutional state there is a crime counteraction problem. In the modern Russian Federation safety problems from the negative social phenomena and processes force scientists, public agents and ordinary citizens to investigate constantly such determinants and the reasons (destabilizers of safety of society and the constitutional state, to eliminate their consequences. Such problems as are urgent now: increase in information on ways and consequences of violence in the mass media (MM, the Internet, computer games, traditional physical abuse. The number of questions and assessment by citizens of consequences of the conducted terrorist attacks and infringement of life of citizens causes. The accounting of the specified problems and versions of decisions in law-enforcement practice, will allow to promote as a result efficiency of prevention of offenses and crimes and will bring closer modern Russia to ideal model of the constitutional state with real civil society. In article the author designates a number of the legal and social destabilizers of safety existing now in the Russian society and the state, proposes the solution of their negative impact on society within tactics of crime control.

  14. PADI4 acts as a coactivator of Tal1 by counteracting repressive histone arginine methylation

    Science.gov (United States)

    Kolodziej, Stephan; Kuvardina, Olga N.; Oellerich, Thomas; Herglotz, Julia; Backert, Ingo; Kohrs, Nicole; Buscató, Estel. La; Wittmann, Sandra K.; Salinas-Riester, Gabriela; Bonig, Halvard; Karas, Michael; Serve, Hubert; Proschak, Ewgenij; Lausen, Jörn

    2014-05-01

    The transcription factor Tal1 is a critical activator or repressor of gene expression in hematopoiesis and leukaemia. The mechanism by which Tal1 differentially influences transcription of distinct genes is not fully understood. Here we show that Tal1 interacts with the peptidylarginine deiminase IV (PADI4). We demonstrate that PADI4 can act as an epigenetic coactivator through influencing H3R2me2a. At the Tal1/PADI4 target gene IL6ST the repressive H3R2me2a mark triggered by PRMT6 is counteracted by PADI4, which augments the active H3K4me3 mark and thus increases IL6ST expression. In contrast, at the CTCF promoter PADI4 acts as a repressor. We propose that the influence of PADI4 on IL6ST transcription plays a role in the control of IL6ST expression during lineage differentiation of hematopoietic stem/progenitor cells. These results open the possibility to pharmacologically influence Tal1 in leukaemia.

  15. Muscle cell atrophy induced by HSP gene silencing was counteracted by HSP overexpression

    Science.gov (United States)

    Choi, Inho; Lee, Joo-Hee; Nikawa, Takeshi; Gwag, Taesik; Park, Kyoungsook; Park, Junsoo

    Heat shock proteins (HSP), as molecular chaperones, are known to assist protein quality control under various stresses. Although overexpression of HSP70 was found to contribute to muscle size retention under an unloading condition, it remains largely unclarified whether muscle atrophy is induced by active suppression of HSP expression. In this study, we pre-treated Hsp70 siRNA to rat L6 cells for the HSP gene silencing, and determined myotube diameter, HSP72 expression and anabolic and catabolic signaling activities in the absence or presence of triterpene celastrol (CEL), the HSP70 inducer. Relative to a negative control (NC), muscle cell diameter was reduced 0.89-fold in the siRNA-treated group, increased 1.2-fold in the CEL-treated group and retained at the size of NC in the siRNA+CEL group. HSP72 expression was decreased 0.35-fold by siRNA whereas the level was increased 6- to 8-fold in the CEL and siRNA+CEL groups. Expression of FoxO3 and atrogin-1 was increased 1.8- to 4.8-fold by siRNA, which was abolished by CEL treatment. Finally, phosphorylation of Akt1, S6K and ERK1/2 was not affected by siRNA, but was elevated 2- to 6-fold in the CEL and siRNA+CEL groups. Taken together, HSP downregulation by Hsp gene silencing led to muscle cell atrophy principally via increases in catabolic activities and that such anti-atrophic effect was counteracted by HSP overexpression.

  16. Counteraction between overshadowing and degraded contingency treatments: support for the extended comparator hypothesis.

    Science.gov (United States)

    Urcelay, Gonzalo P; Miller, Ralph R

    2006-01-01

    Four experiments using rats in a Pavlovian lick-suppression preparation investigated the effects of combining 2 treatments known for their response-decrementing effects, namely, overshadowing and degraded contingency. Contrary to most contemporary learning theories, the extended comparator hypothesis predicts that these 2 treatments will counteract each other, and therefore, less of a decrement in conditioned responding should be observed than with either treatment alone. Experiments 1 and 2 confirmed this prediction in first-order conditioning and sensory preconditioning preparations, respectively. Experiment 3 demonstrated that posttraining extinction of the training context resulted in a recovery from degraded contingency and reversed the counteractive effect on overshadowing. Finally, Experiment 4 demonstrated that posttraining extinction of the overshadowing stimulus resulted in recovery from simple overshadowing and also reversed the counteractive effect on degraded contingency. These results are consistent with the extended comparator hypothesis but not traditional or recent acquisition-focused models.

  17. 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.

  18. 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.

  19. Housing in pyramid counteracts neuroendocrine and oxidative stress caused by chronic restraint in rats.

    Science.gov (United States)

    Bhat, M Surekha; Rao, Guruprasad; Murthy, K Dilip; Bhat, P Gopalakrishna

    2007-03-01

    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.

  20. Dexamethasone counteracts the effect of prolactin on islet function: implications for islet regulation in late pregnancy.

    Science.gov (United States)

    Weinhaus, A J; Bhagroo, N V; Brelje, T C; Sorenson, R L

    2000-04-01

    Islets undergo a number of up-regulatory changes to meet the increased demand for insulin during pregnancy, including increased insulin secretion and beta-cell proliferation. It has been shown that elevated lactogenic hormone is directly responsible for these changes, which occur in a phasic pattern, peaking on day 15 of pregnancy and returning to control levels by day 20 (term). As placental lactogen levels remain elevated through late gestation, it was of interest to determine whether glucocorticoids (which increase during late gestation) could counteract the effects of lactogens on insulin secretion, beta-cell proliferation, and apoptosis. We found that insulin secretion measured over 24 h in culture and acute secretion measured over 1 h in response to high glucose were increased at least 2-fold by PRL treatment after 6 days in culture. Dexamethasone (DEX) treatment had a significant inhibitory effect on secretion in a dose-dependent manner at concentrations greater than 1 nM. At 100 nM, a concentration equivalent to the plasma corticosteroid level during late pregnancy, DEX inhibited secretion to below control levels. The addition of DEX (>1 nM) inhibited secretion from PRL-treated islets to levels similar to those produced by DEX treatment alone. Bromodeoxyuridine (10 microM) staining for the final 24 h of a 6-day culture showed that PRL treatment increased cell proliferation 6-fold over the control level. DEX treatment alone (1-1000 nM) did not reduce cell division below the control level, but significantly inhibited the rate of division in PRL-treated islets. YoYo-1, an ultrasensitive fluorescent nucleic acid stain, was added (1 microM; 8 h) to the medium after 1-3 days of culture to examine cell death. Islets examined under confocal microscopy showed that DEX treatment (100 nM) increased the number of cells with apoptotic nuclear morphologies. This was quantified by counting the number of YoYo-labeled nuclei per islet under conventional epifluorescence

  1. 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.

  2. Red Seaweed (Hypnea Bryodies and Melanothamnus Somalensis) Extracts Counteracting Azoxymethane-Induced Hepatotoxicity in Rats

    Science.gov (United States)

    Ibrahim Waly, Mostafa; Al Alawi, Ahmed Ali; Al Marhoobi, Insaaf Mohammad; Rahman, Mohammad Shafiur

    2016-12-01

    Background: Azoxymethane (AOM) is a well-known colon cancer-inducing agent in experimental animals via mechanisms that include oxidative stress in rat colon and liver tissue. Few studies have investigated AOM-induced oxidative stress in rat liver tissue. Red seaweeds of the genera Hypnea Bryodies and Melanothamnus Somalensis are rich in polyphenolic compounds that may suppress cancer through antioxidant properties, yet limited research has been carried out to investigate their anti-carcinogenic and antioxidant influence against AOM-induced oxidative stress in rat liver. Objective: This study aims to determine protective effects of red seaweed (Hypnea Bryodies and Melanothamnus Somalensis) extracts against AOM-induced hepatotoxicity and oxidative stress. Materials and Methods: Sprague–Dawley rats received intraperitoneal injections of AOM, 15 mg/kg body weight, once a week for two consecutive weeks and then orally administered red seaweed (100 mg/kg body-weight) extracts for sixteen weeks. At the end of the experiment all animals were overnight fasted then sacrificed and blood and liver tissues were collected. Results: AOM treatment significantly decreased serum liver markers and induced hepatic oxidative stress as evidenced by increased liver tissue homogenate levels of nitric oxide and malondialdehyde, decreased total antioxidant capacity and glutathione, and inhibition of antioxidant enzymes (catalase, glutathione peroxidase, glutathione S-transferase, glutathione reductase and superoxide dismutase). Both red seaweed extracts abolished the AOM-associated oxidative stress and protected against liver injury as evidenced by increased serum levels of liver function markers. In addition, histological findings confirmed protective effects of the two red seaweed extracts against AOM-induced liver injury. Conclusion: Our findings indicate that red seaweed (Hypnea Bryodies and Melanothamnus Somalensis) extracts counteracted oxidative stress-induced hepatotoxicity in a

  3. Propolis counteracts some threats to honey bee health

    Science.gov (United States)

    Honey bee (Apis mellifera) populations in North America and Europe are currently experiencing high and unsustainable annual losses. It is critically important to understand the impact of individual stressors and the interactions among stressors in order to develop solutions to increase colony health...

  4. 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

  5. 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

    In this study a methodology is applied to quantify the effect of evaporator maldistributionon operating costs of airewater heat pumps. The approach is used to investigate the cost-effectivenessof two technologies enabling to counteract maldistribution: a flash gasbypass setup and the individual...

  6. Adipose gene expression patterns of weight gain suggest counteracting steroid hormone synthesis

    NARCIS (Netherlands)

    Schothorst, van E.M.; Franssen-Hal, van N.L.W.; Schaap, M.M.; Pennings, J.; Hoebee, B.; Keijer, J.

    2005-01-01

    VAN SCHOTHORST, EVERT M., NICOLE FRANSSEN-VAN HAL, MIRJAM M. SCHAAP, JEROEN PENNINGS, BARBARA HOEBEE, AND JAAP KEIJER. Adipose gene expression patterns of weight gain suggest counteracting steroid hormone synthesis. Obes Res. 2005;13:1031-1041. Objective: To identify early molecular changes in weigh

  7. Allured or alarmed: Counteractive control responses to food temptations in the brain

    NARCIS (Netherlands)

    Smeets, P.A.M.; Kroese, F.M.; Evers, C.; Ridder, de D.T.D.

    2013-01-01

    Typically, it is believed that palatable, high caloric foods signal reward and trigger indulgent responses. However, Counteractive Control Theory suggests that, to the extent that people are concerned about their weight, a confrontation with palatable foods should also trigger ‘alarm bell responses’

  8. Carbon Monoxide Alleviates Wheat Seed Germination Inhibition and Counteracts Lipid Peroxidation Mediated by Salinity

    Institute of Scientific and Technical Information of China (English)

    Sheng Xu; Zhi-Sheng Sa; Ze-Yu Cao; Wei Xuan; Ben-Kai Huang; Teng-Fang Ling; Qiong-Ying Hu; Wen-Biao Shen

    2006-01-01

    Recently in animals, endogenous carbon monoxide (CO), like nitric oxide, was implicated as another important physiological messenger or bioactive molecule. However, little information is known about the physiological roles of CO in the whole plant. In the present study, we report that different concentrations of the CO donor hematin (0.1,1.0 and 10.0μmol/L) alleviated wheat (Triticum aestivum L. Yangmai 158) seed germination inhibition caused by 250 mmol/L NaCl stress in a dose-dependent manner. These responses were also proved by the addition of different gaseous CO aqueous solutions from 0.1% to 100.0% of saturation.Among these treatments, the effect of 1.0 μmol/L hematin and 1.0% saturation of CO aqueous solution were the most obvious. Furthermore, compared with non-hematin treatment, the degradation of storage reserves In wheat seeds was also accelerated. Time-course analyses showed that application of hematin dose-dependently increased the activities of superoxide dismutase, catalase, ascorbate peroxidase, and guaiacol peroxidase activities, thus decreasing the lipid peroxidation in germinating wheat seed subjected to saltstress. Meanwhile, the responses of hematin were specific for CO because the addition of the CO scavenger hemoglobin (0.2 g/L) blocked the various actions of 1.0 μ mol/L hematin. Taken together, the results of the present study demonstrate that CO, at a Iow concentration, is able to attenuate the seed germination inhibition produced by salinity stress and counteract the lipid peroxidation in germinating wheat seeds.

  9. High brachytherapy doses can counteract hypoxia in cervical cancer—a modelling study

    Science.gov (United States)

    Lindblom, Emely; Dasu, Alexandru; Beskow, Catharina; Toma-Dasu, Iuliana

    2017-01-01

    Tumour hypoxia is a well-known adverse factor for the outcome of radiotherapy. For cervical tumours in particular, several studies indicate large variability in tumour oxygenation. However, clinical evidence shows that the management of cervical cancer including brachytherapy leads to high rate of success. It was the purpose of this study to investigate whether the success of brachytherapy for cervical cancer, seemingly regardless of oxygenation status, could be explained by the characteristics of the brachytherapy dose distributions. To this end, a previously used in silico model of tumour oxygenation and radiation response was further developed to simulate the treatment of cervical cancer employing a combination of external beam radiotherapy and intracavitary brachytherapy. Using a clinically-derived brachytherapy dose distribution and assuming a homogeneous dose delivered by external radiotherapy, cell survival was assessed on voxel level by taking into account the variation of sensitivity with oxygenation as well as the effects of repair, repopulation and reoxygenation during treatment. Various scenarios were considered for the conformity of the brachytherapy dose distribution to the hypoxic region in the target. By using the clinically-prescribed brachytherapy dose distribution and varying the total dose delivered with external beam radiotherapy in 25 fractions, the resulting values of the dose for 50% tumour control, D 50, were in agreement with clinically-observed values for high cure rates if fast reoxygenation was assumed. The D 50 was furthermore similar for the different degrees of conformity of the brachytherapy dose distribution to the tumour, regardless of whether the hypoxic fraction was 10%, 25%, or 40%. To achieve 50% control with external RT only, a total dose of more than 70 Gy in 25 fractions would be required for all cases considered. It can thus be concluded that the high doses delivered in brachytherapy can counteract the increased

  10. Acute caloric restriction counteracts hepatic bile acid and cholesterol deficiency in morbid obesity.

    Science.gov (United States)

    Straniero, S; Rosqvist, F; Edholm, D; Ahlström, H; Kullberg, J; Sundbom, M; Risérus, U; Rudling, M

    2017-05-01

    Bile acid (BA) synthesis is regulated by BA signalling in the liver and by fibroblast growth factor 19 (FGF19), synthesized and released from the intestine. In morbid obesity, faecal excretion and hepatic synthesis of BAs and cholesterol are strongly induced and caloric restriction reduces their faecal excretion considerably. We hypothesized that the high intestinal food mass in morbidly obese subjects promotes faecal excretion of BAs and cholesterol, thereby creating a shortage of both BAs and cholesterol in the liver. Ten morbidly obese women (BMI 42 ± 2.6 kg m(-2) ) were monitored on days 0, 3, 7, 14 and 28 after beginning a low-calorie diet (800-1100 kcal day(-1) ). Serum was collected and liver size and fat content determined. Synthesis of BAs and cholesterol was evaluated from serum markers, and the serum levels of lipoproteins, BAs, proprotein convertase subtilisin/kexin type 9 (PCSK9), insulin, glucose and FGF19 were monitored. Fifty-four nonobese women (BMI cholesterol and serum levels of BAs and PCSK9 were elevated in the obese group compared to controls. Already after 3 days on a low-calorie diet, BA and cholesterol synthesis and serum BA and PCSK9 levels normalized, whereas LDL cholesterol increased. FGF19 and triglyceride levels were unchanged, and liver volume was reduced by 10%. The results suggest that hepatic BAs and cholesterol are deficient in morbid obesity. Caloric restriction rapidly counteracts these deficiencies, normalizing BA and cholesterol synthesis and circulating PCSK9 levels, indicating that overproduction of cholesterol in enlarged peripheral tissues cannot explain this phenotype. We propose that excessive food intake promotes faecal loss of BAs and cholesterol contributing to their hepatic deficiencies. © 2017 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

  11. 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.

  12. Counteracting Byzantine Adversaries with Network Coding: An Overhead Analysis

    CERN Document Server

    Kim, MinJi; Barros, Joao

    2008-01-01

    Network coding increases throughput and is robust against failures and erasures. However, since it allows mixing of information within the network, a single corrupted packet generated by a Byzantine attacker can easily contaminate the information to multiple destinations. In this paper, we study the transmission overhead associated with detecting Byzantine adversaries at a trusted node using network coding. We consider three different schemes: end-to-end error correction, packet-based Byzantine detection scheme, and generation-based Byzantine detection scheme. In end-to-end error correction, it is known that we can correct up to the min-cut between the source and destinations. However, if we use Byzantine detection schemes, we can detect polluted data, drop them, and therefore, only transmit valid data. For the dropped data, the destinations perform erasure correction, which is computationally lighter than error correction. We show that, with enough attackers present in the network, Byzantine detection scheme...

  13. 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

  14. Short-Term Summer Inundation as a Measure to Counteract Acidification in Rich Fens.

    Directory of Open Access Journals (Sweden)

    Ivan S Mettrop

    Full Text Available In regions with intensive agriculture, water level fluctuation in wetlands has generally become constricted within narrow limits. Water authorities are, however, considering the re-establishment of fluctuating water levels as a management tool in biodiverse, base-rich fens ('rich fens'. This includes temporary inundation with surface water from ditches, which may play an important role in counteracting acidification in order to conserve and restore biodiversity. Inundation may result in an increased acid neutralizing capacity (ANC for two reasons: infiltration of base-rich inundation water into peat soils, and microbial alkalinity generation under anaerobic conditions. The main objectives of this study were to test whether short-term (2 weeks summer inundation is more effective than short-term winter inundation to restore the ANC in the upper 10 cm of non-floating peat soils, and to explain potential differences. Large-scale field experiments were conducted for five years in base-rich fens and Sphagnum-dominated poor fens. Winter inundation did not result in increased porewater ANC, because infiltration was inhibited in the waterlogged peat and evapotranspiration rates were relatively low. Also, low temperatures limit microbial alkalinity generation. In summer, however, when temperature and evapotranspiration rates are higher, inundation resulted in increased porewater Ca and HCO3- concentrations, but only in areas with characteristic rich fen bryophytes. This increase was not only due to stronger infiltration into the soil, but also to higher microbial alkalinity generation under anaerobic conditions. In contrast, porewater ANC did not increase in Sphagnum-plots as a result of the ability of Sphagnum spp. to acidify their environment. In both rich and poor fens, flooding-induced P-mobilization remained sufficiently low to safeguard P-limited vegetation. NO3(- and NH4(+ dynamics showed no considerable changes either. In conclusion, short

  15. Neurophysiological maturation in adolescence - vulnerability and counteracting addiction to alcohol.

    Science.gov (United States)

    Chwedorowicz, Roman; Skarżyński, Henryk; Pucek, Weronika; Studziński, Tadeusz

    2017-03-22

    The results of contemporary studies confirm the formation of two neural networks in the brain during the period of adolescence. The first is defined as emotional, located in the limbic system, develops earlier, quicker, and more intensively than the second one in the prefrontal cortex, called the judgement network, which fulfils the role of control and inhibition of emotional reactions. The domination of the emotional network in adolescence is manifested by hyperactivity of the limbic system, accompanied by intensified undertaking of courageous, reckless, risky, or even sometimes dangerous actions, so very characteristic in the maturation. The aim of the article is to present the state of the art in the field of latest achievements in experimental neurophysiology related to the maturation of the structural end functional processes in adolescents, and to alcohol vulnerability. Alcohol effect initiation starts in early adolescence, and therefore is connected with alcohol abuse and addiction in adulthood, which confirms the necessity for provision of an early prophylactic protection for juveniles, even before entering the phase of early adolescence. Some electrophysiological characteristics, such as low P3 amplitude of the Event-Related Potential (ERP) and Event-Related Oscillations (EROs), are manifested by their high risk offspring, and are considered to be biological markers (endophenotypes) of a predisposition to develop alcohol use disorders. Electroencephalographic oscillations induced within the range of the theta and delta waves (Event-Related Oscillation- ERO), considered as endophenotypes and markers of increased vulnerability for addiction, present three groups of genes and three types of neurotransmitters, with gamma aminobutyric acid, acetylcholine and glutamate as neurotransmitters in the central nervous system. A new research approach consisting in the application of electroencephalographic methods and techniques in developmental and genetic studies of

  16. Doxorubicin-induced oxidative stress in rats is efficiently counteracted by dietary anthocyanin differently enriched strawberry (Fragaria × ananassa Duch.).

    Science.gov (United States)

    Diamanti, Jacopo; Mezzetti, Bruno; Giampieri, Francesca; Alvarez-Suarez, José M; Quiles, José L; Gonzalez-Alonso, Adrian; Ramirez-Tortosa, Maria del Carmen; Granados-Principal, Sergio; Gonzáles-Paramás, Ana M; Santos-Buelga, Celestino; Battino, Maurizio

    2014-05-07

    This study investigated the effects of two different strawberry cultivars, Adria and Sveva, against doxorubicin (DOX)-induced toxicity in rats. A controlled dietary intervention was conducted over 16 weeks with four groups: (i) normal diet; (ii) normal diet + DOX injection; (iii) Adria supplementation + DOX injection; and (iv) Sveva supplementation + DOX injection. Sveva presented higher total antioxidant capacity value and phenol and and vitamin C levels than Adria, which in turn presented higher anthocyanin contents. DOX drastically increased lymphocyte DNA damage, liver biomarkers of protein and lipid oxidation, and mitochondrial ROS content and markedly decreased plasma retinol level, liver antioxidant enzymes, and mitochondrial functionality. After 2 months of strawberry supplementation, rats presented a significant reduction of DNA damage and ROS concentration and a significant improvement of oxidative stress biomarkers, antioxidant enzyme activities, and mitochondrial performance. These results suggest that strawberry supplementation can counteract DOX toxicity, confirming the potential health benefit of strawberry in vivo against oxidative stress.

  17. Propolis Counteracts Some Threats to Honey Bee Health

    Science.gov (United States)

    Simone-Finstrom, Michael; Borba, Renata S.; Wilson, Michael; Spivak, Marla

    2017-01-01

    Honey bees (Apis mellifera) are constantly dealing with threats from pathogens, pests, pesticides and poor nutrition. It is critically important to understand how honey bees’ natural immune responses (individual immunity) and collective behavioral defenses (social immunity) can improve bee health and productivity. One form of social immunity in honey bee colonies is the collection of antimicrobial plant resins and their use in the nest architecture as propolis. We review research on the constitutive benefits of propolis on the honey bee immune system, and its known therapeutic, colony-level effects against the pathogens Paenibacillus larvae and Ascosphaera apis. We also review the limited research on the effects of propolis against other pathogens, parasites and pests (Nosema, viruses, Varroa destructor, and hive beetles) and how propolis may enhance bee products such as royal jelly and honey. Although propolis may be a source of pesticide contamination, it also has the potential to be a detoxifying agent or primer of detoxification pathways, as well as increasing bee longevity via antioxidant-related pathways. Throughout this paper, we discuss opportunities for future research goals and present ways in which the beekeeping community can promote propolis use in standard colonies, as one way to improve and maintain colony health and resiliency. PMID:28468244

  18. Propolis Counteracts Some Threats to Honey Bee Health.

    Science.gov (United States)

    Simone-Finstrom, Michael; Borba, Renata S; Wilson, Michael; Spivak, Marla

    2017-04-29

    Honey bees (Apis mellifera) are constantly dealing with threats from pathogens, pests, pesticides and poor nutrition. It is critically important to understand how honey bees' natural immune responses (individual immunity) and collective behavioral defenses (social immunity) can improve bee health and productivity. One form of social immunity in honey bee colonies is the collection of antimicrobial plant resins and their use in the nest architecture as propolis. We review research on the constitutive benefits of propolis on the honey bee immune system, and its known therapeutic, colony-level effects against the pathogens Paenibacillus larvae and Ascosphaera apis. We also review the limited research on the effects of propolis against other pathogens, parasites and pests (Nosema, viruses, Varroa destructor, and hive beetles) and how propolis may enhance bee products such as royal jelly and honey. Although propolis may be a source of pesticide contamination, it also has the potential to be a detoxifying agent or primer of detoxification pathways, as well as increasing bee longevity via antioxidant-related pathways. Throughout this paper, we discuss opportunities for future research goals and present ways in which the beekeeping community can promote propolis use in standard colonies, as one way to improve and maintain colony health and resiliency.

  19. 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

  20. Ghrelin counteracts salt-induced hypertension via promoting diuresis and renal nitric oxide production in Dahl rats.

    Science.gov (United States)

    Aoki, Hirotaka; Nakata, Masanori; Dezaki, Katsuya; Lu, Ming; Gantulga, Darambazar; Yamamoto, Keiji; Shimada, Kazuyuki; Kario, Kazuomi; Yada, Toshihiko

    2013-01-01

    Ghrelin is the endogenous ligand for the growth hormone-secretagogue receptor expressed in various tissues including the heart, blood vessels and kidney. This study sought to determine the effects of long-term treatment with ghrelin (10 nmol/kg, twice a day, intraperitoneally) on the hypertension induced by high salt (8.0% NaCl) diet in Dahl salt-sensitive hypertensive (DS) rats. Systolic blood pressure (SBP) was measured by a tail cuff method. During the treatment period for 3 weeks, high salt diet increased blood pressure compared to normal salt (0.3% NaCl) diet, and this hypertension was partly but significantly (P<0.01) attenuated by simultaneous treatment with ghrelin. Ghrelin significantly increased urine volume and tended to increase urine Na⁺ excretion. Furthermore, ghrelin increased urine nitric oxide (NO) excretion and tended to increase renal neuronal nitric oxide synthase (nNOS) mRNA expression. Ghrelin did not alter the plasma angiotensin II level and renin activity, nor urine catecholamine levels. Furthermore, ghrelin prevented the high salt-induced increases in heart thickness and plasma ANP mRNA expression. These results demonstrate that long-term ghrelin treatment counteracts salt-induced hypertension in DS rats primarily through diuretic action associated with increased renal NO production, thereby exerting cardio-protective effects.

  1. 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.

  2. The University of the Third Age as an institution counteracting marginalization of older people

    Directory of Open Access Journals (Sweden)

    Aleksandra Marcinkiewicz

    2011-12-01

    Full Text Available The article presents the role of the University of the Third Age in counteracting the effects of marginalization of the elderly. The history of the University of the Third Age is presented and also different models of this institution are characterized. The paper presents new trends in research conducted by participants of the U3A and shown their relation to marginalization

  3. 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.

  4. By counteracting gravity, triceps surae sets both kinematics and kinetics of gait.

    Science.gov (United States)

    Honeine, Jean-Louis; Schieppati, Marco; Gagey, Oliver; Do, Manh-Cuong

    2014-02-01

    In the single-stance phase of gait, gravity acting on the center of mass (CoM) causes a disequilibrium torque, which generates propulsive force. Triceps surae activity resists gravity by restraining forward tibial rotation thereby tuning CoM momentum. We hypothesized that time and amplitude modulation of triceps surae activity determines the kinematics (step length and cadence) and kinetics of gait. Nineteen young subjects participated in two experiments. In the gait initiation (GI) protocol, subjects deliberately initiated walking at different velocities for the same step length. In the balance-recovery (BR) protocol, subjects executed steps of different length after being unexpectedly released from an inclined posture. Ground reaction force was recorded by a large force platform and electromyography of soleus, gastrocnemius medialis and lateralis, and tibialis anterior muscles was collected by wireless surface electrodes. In both protocols, the duration of triceps activity was highly correlated with single-stance duration (GI, R (2) = 0.68; BR, R (2) = 0.91). In turn, step length was highly correlated with single-stance duration (BR, R (2) = 0.70). Control of CoM momentum was obtained by decelerating the CoM fall via modulation of amplitude of triceps activity. By modulation of triceps activity, the central nervous system (CNS) varied the position of CoM with respect to the center of pressure (CoP). The CoM-CoP gap in the sagittal plane was determinant for setting the disequilibrium torque and thus walking velocity. Thus, by controlling the gap, CNS-modified walking velocity (GI, R (2) = 0.86; BR, R (2) = 0.92). This study is the first to highlight that by merely counteracting gravity, triceps activity sets the kinematics and kinetics of gait. It also provides evidence that the surge in triceps activity during fast walking is due to the increased requirement of braking the fall of CoM in late stance in order to perform a smoother step-to-step transition.

  5. 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.

  6. 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...

  7. Herpes simplex virus 1 counteracts viperin via its virion host shutoff protein UL41.

    Science.gov (United States)

    Shen, Guanghui; Wang, Kezhen; Wang, Shuai; Cai, Mingsheng; Li, Mei-li; Zheng, Chunfu

    2014-10-01

    The interferon (IFN)-inducible viperin protein restricts a broad range of viruses. However, whether viperin plays a role during herpes simplex virus 1 (HSV-1) infection is poorly understood. In the present study, it was shown for the first time that wild-type (WT) HSV-1 infection couldn't induce viperin production, and ectopically expressed viperin inhibited the replication of UL41-null HSV-1 but not WT viruses. The underlying molecular mechanism is that UL41 counteracts viperin's antiviral activity by reducing its mRNA accumulation.

  8. Semi-Supervised Learning Techniques in AO Applications: A Novel Approach To Drift Counteraction

    Science.gov (United States)

    De Vito, S.; Fattoruso, G.; Pardo, M.; Tortorella, F.; Di Francia, G.

    2011-11-01

    In this work we proposed and tested the use of SSL techniques in the AO domain. The SSL characteristics have been exploited to reduce the need for costly supervised samples and the effects of time dependant drift of state-of-the-art statistical learning approaches. For this purpose, an on-field recorded one year long atmospheric pollution dataset has been used. The semi-supervised approach benefitted from the use of updated unlabeled samples, adapting its knowledge to the slowly changing drift effects. We expect that semi-supervised learning can provide significant advantages to the performance of sensor fusion subsystems in artificial olfaction exhibiting an interesting drift counteraction effect.

  9. 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 lactate dehydrogenase release and DNA damage in both fibroblast cultures. These findings indicate that α...

  10. 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 PURPOSE: 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. METHODS: 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. RESULTS: 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

  11. Autofrettage to Counteract Coefficient of Thermal Expansion Mismatch in Cryogenic Pressurized Pipes with Metallic Liners

    Science.gov (United States)

    Wen, Ed; Barbero, Ever; Tygielski, Phlip; Turner, James E. (Technical Monitor)

    2001-01-01

    Composite feedlines with metal liners have the potential to reduce weight/cost while providing the same level of permeation resistance and material compatibility of all-metal feedlines carrying cryogenic propellants in spacecraft. The major technical challenges are the large difference in Coefficient of Thermal Expansion between the liner and the composite, and the manufacturing method required to make a very thin liner with the required strength and dimensional tolerance. This study investigates the use of autofrettage (compressive preload) to counteract Coefficient of Thermal Expansion when pre-pressurization procedures cannot be used to solve this problem. Promising materials (aluminum 2219, Inconel 718, nickel, nickel alloy) and manufacturing techniques (chemical milling, electroplating) are evaluated to determine the best liner candidates. Robust, autofrettaged feedlines with a low Coefficient of Thermal Expansion liner (Inconel 718 or nickel alloy) are shown to successfully counteract mismatch at LOX temperature. A new concept, autofrettage by temperature, is introduced for high Coefficient of Thermal Expansion materials (aluminum and pure nickel) where pressure cannot be used to add compressive preload.

  12. Rac1 GTPase silencing counteracts microgravity-induced effects on osteoblastic cells.

    Science.gov (United States)

    Guignandon, Alain; Faure, Céline; Neutelings, Thibaut; Rattner, Aline; Mineur, Pierre; Linossier, Marie-Thérèse; Laroche, Norbert; Lambert, Charles; Deroanne, Christophe; Nusgens, Betty; Demets, René; Colige, Alain; Vico, Laurence

    2014-09-01

    Bone cells exposed to real microgravity display alterations of their cytoskeleton and focal adhesions, two major mechanosensitive structures. These structures are controlled by small GTPases of the Ras homology (Rho) family. We investigated the effects of RhoA, Rac1, and Cdc42 modulation of osteoblastic cells under microgravity conditions. Human MG-63 osteoblast-like cells silenced for RhoGTPases were cultured in the automated Biobox bioreactor (European Space Agency) aboard the Foton M3 satellite and compared to replicate ground-based controls. The cells were fixed after 69 h of microgravity exposure for postflight analysis of focal contacts, F-actin polymerization, vascular endothelial growth factor (VEGF) expression, and matrix targeting. We found that RhoA silencing did not affect sensitivity to microgravity but that Rac1 and, to a lesser extent, Cdc42 abrogation was particularly efficient in counteracting the spaceflight-related reduction of the number of focal contacts [-50% in silenced, scrambled (SiScr) controls vs. -15% for SiRac1], the number of F-actin fibers (-60% in SiScr controls vs. -10% for SiRac1), and the depletion of matrix-bound VEGF (-40% in SiScr controls vs. -8% for SiRac1). Collectively, these data point out the role of the VEGF/Rho GTPase axis in mechanosensing and validate Rac1-mediated signaling pathways as potential targets for counteracting microgravity effects. © FASEB.

  13. Piracetam counteracts the effects of amitriptyline on inhibitory avoidance in CD1 mice.

    Science.gov (United States)

    Everss, Estrella; Arenas, M Carmen; Vinader-Caerols, Concepción; Monleón, Santiago; Parra, Andrés

    2005-04-30

    The purpose of the present work was to study the effects of amitriptyline on animal cognition in relation to some characteristics of its therapeutic effects. The modulation of acute and chronic effects of amitriptyline on inhibitory avoidance in male and female mice by piracetam was investigated. In Experiment 1, mice were subjected to the training phase of inhibitory avoidance conditioning 60 min after acute piracetam (100 mg/kg) or physiological saline administration. Immediately after the behavioural task, they received a single injection of the tricyclic antidepressant amitriptyline (30 mg/kg) or physiological saline. Twenty-four hours later, subjects were tested for avoidance. In Experiment 2, the same doses of amitriptyline and piracetam were chronically administered. Mice were subjected to the training phase of inhibitory avoidance on the 22nd day, and to the test phase 24 h later. Forty-five minutes after test, subjects explored the elevated plus-maze for 5 min in order to assess whether the effects of amitriptyline on avoidance performance may reflect general behavioural changes. Results obtained were that: (a) acute and chronic amitriptyline impaired inhibitory avoidance of male and female mice, (b) piracetam counteracted the effect of acutely administered amitriptyline on inhibitory avoidance, and (c) piracetam counteracted the effects of chronically administered amitriptyline in males but not females in the same learning task. These effects do not seem to be mediated by non-specific drug effects on spontaneous motor activity or anxiety.

  14. Leishmania amazonensis exhibits phosphatidylserine-dependent procoagulant activity, a process that is counteracted by sandfly saliva

    Directory of Open Access Journals (Sweden)

    Natalia Cadaxo Rochael

    2013-09-01

    Full Text Available Leishmania parasites expose phosphatidylserine (PS on their surface, a process that has been associated with regulation of host's immune responses. In this study we demonstrate that PS exposure by metacyclic promastigotes of Leishmania amazonensis favours blood coagulation. L. amazonensis accelerates in vitro coagulation of human plasma. In addition, L. amazonensis supports the assembly of the prothrombinase complex, thus promoting thrombin formation. This process was reversed by annexin V which blocks PS binding sites. During blood meal, Lutzomyia longipalpis sandfly inject saliva in the bite site, which has a series of pharmacologically active compounds that inhibit blood coagulation. Since saliva and parasites are co-injected in the host during natural transmission, we evaluated the anticoagulant properties of sandfly saliva in counteracting the procoagulant activity of L. amazonensis . Lu. longipalpis saliva reverses plasma clotting promoted by promastigotes. It also inhibits thrombin formation by the prothrombinase complex assembled either in phosphatidylcholine (PC/PS vesicles or in L. amazonensis . Sandfly saliva inhibits factor X activation by the intrinsic tenase complex assembled on PC/PS vesicles and blocks factor Xa catalytic activity. Altogether our results show that metacyclic promastigotes of L. amazonensis are procoagulant due to PS exposure. Notably, this effect is efficiently counteracted by sandfly saliva.

  15. Tissue inhibitor of metalloproteinase-1 counteracts glucolipotoxicity in the pancreatic β-cell line INS-1

    Institute of Scientific and Technical Information of China (English)

    JIANG Hong-wei; ZHU Han-yu; WANG Jian-zhong; FU Bo; L(U) Yang; HONG Quan; XIE Yuan-sheng; CHEN Xiang-mei

    2011-01-01

    Background Glucolipotoxicity might play an important role in the β cell decompensation stage during the development of obesity-associated type 2 diabetes.Tissue inhibitor of metalloproteinase-1 (TIMP-1) inhibits matrix metalloproteinase (MMP) activity and regulates proliferation and apoptosis of a variety of cell types,including pancreatic β-cells.In the present study,we investigated whether TIMP-1 counteracts glucolipotoxicity in the pancreatic β-cell line INS-1.Methods INS-1 cells were incubated in normal or high glucose,with or without palmitate (0.4 mmol/L),in the presence of TIMP-1 or MMP inhibitor GM60001.In some experiments,cells were pretreated with phosphatidylinositol-3 (Pl-3) kinase inhibitor,LY294002 or wortmannin.The amount of dead INS-1 cells was determined by HO342 and propidium iodide staining.Akt phosphorylation was evaluated by Western blotting analysis to investigate a possible mechanism of TIMP-1's action.Results TIMP-1 protected INS-1 cells from glucolipotoxicity independent of MMP inhibition.TIMP-1 stimulated Akt phosphorylation.Inhibition of the PI-3 kinase pathway abolished the survival effect of TIMP-1.Conclusion TIMP-1 may counteract glucolipotoxicity induced β-cell death via a PI-3 kinase pathway.

  16. 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.

  17. Compensatory up-regulation of cardiac SR Ca2+-pump by heat-shock counteracts SR Ca2+-channel activation by ischemia/reperfusion.

    Science.gov (United States)

    O'Brien, P J; Li, G O; Locke, M; Klabunde, R E; Ianuzzo, C D

    1997-08-01

    We tested the hypothesis that heat-shock protected myocardial Ca2+-cycling by sarcoplasmic reticulum from ischemia and reperfusion (I/R) injury. Twenty-four hours after increasing body temperature to 42 degrees C for 15 min, rat hearts were isolated, Langendorff-perfused, and subjected to 30 min ischemia then 30 min reperfusion. Left ventricles were homogenized and their ionized Ca2+ concentration monitored with indo- during Ca2+-uptake in the presence and absence of the Ca2+-release channel (CRC) modulator ryanodine. Tissue content of heat-shock protein 72 (HSP 72) was analyzed. Exposure to I/R resulted in a 37% enhancement of CRC activity but no effect on Ca2+-pumping activity, resulting in 25% decreased net Ca2+-uptake activity. Pre-exposure to heat-shock resulted in a 10-fold increase in HSP 72, and a 25% enhancement of maximal Ca2+-pumping activity which counteracted the effect of I/R on CRC and net Ca2+-uptake activities. This protection of SR Ca2+-cycling was associated with partial protection of myocardial physiological performance. Net Ca2+-uptake activity was correlated with the left ventricular developed pressure and its rate of change. We conclude that one of the mechanisms by which heat-shock protects myocardium from I/R injury is to upregulate SR Ca2+-pumping activity to counteract the enhanced SR Ca2+-release produced by I/R.

  18. 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...

  19. 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......, adipose tissue inflammation and glucose intolerance....

  20. (−)-Englerin A-evoked Cytotoxicity Is Mediated by Na+ Influx and Counteracted by Na+/K+-ATPase*

    Science.gov (United States)

    Ludlow, Melanie J.; Gaunt, Hannah J.; Rubaiy, Hussein N.; Musialowski, Katie E.; Blythe, Nicola M.; Vasudev, Naveen S.; Muraki, Katsuhiko; Beech, David J.

    2017-01-01

    (−)-Englerin A ((−)-EA) has a rapid and potent cytotoxic effect on several types of cancer cell that is mediated by plasma membrane ion channels containing transient receptor potential canonical 4 (TRPC4) protein. Because these channels are Ca2+-permeable, it was initially thought that the cytotoxicity arose as a consequence of Ca2+ overload. Here we show that this is not the case and that the effect of (−)-EA is mediated by a heteromer of TRPC4 and TRPC1 proteins. Both TRPC4 and TRPC1 were required for (−)-EA cytotoxicity; however, although TRPC4 was necessary for the (−)-EA-evoked Ca2+ elevation, TRPC1 was not. TRPC1 either had no role or was a negative regulator of Ca2+ entry. By contrast, both TRPC4 and TRPC1 were necessary for monovalent cation entry evoked by (−)-EA, and (−)-EA-evoked cell death was dependent upon entry of the monovalent cation Na+. We therefore hypothesized that Na+/K+-ATPase might act protectively by counteracting the Na+ load resulting from sustained Na+ entry. Indeed, inhibition of Na+/K+-ATPase by ouabain potently and strongly increased (−)-EA-evoked cytotoxicity. The data suggest that (−)-EA achieves cancer cell cytotoxicity by inducing sustained Na+ entry through heteromeric TRPC1/TRPC4 channels and that the cytotoxic effect of (−)-EA can be potentiated by Na+/K+-ATPase inhibition. PMID:27875305

  1. Counteraction of Trehalose on N, N-Dimethylformamide-Induced Candida rugosa Lipase Denaturation: Spectroscopic Insight and Molecular Dynamic Simulation.

    Directory of Open Access Journals (Sweden)

    Xin Yang

    Full Text Available Candida rugosa lipase (CRL has been widely used as a biocatalyst for non-aqueous synthesis in biotechnological applications, which, however, often suffers significant loss of activity in organic solvent. Experimental results show that trehalose could actively counteract the organic-solvent-induced protein denaturation, while the molecular mechanisms still don't unclear. Herein, CRL was used as a model enzyme to explore the effects of trehalose on the retention of enzymatic activity upon incubation in N,N-dimethylformamide (DMF. Results showed that both catalytic activity and conformation changes of CRL influenced by DMF solvent were inhibited by trehalose in a dose-dependent fashion. The simulations further indicated that the CRL protein unfolded in binary DMF solution, but retained the native state in the ternary DMF/trehalose system. Trehalose as the second osmolyte added into binary DMF solution decreased DMF-CRL hydrogen bonds efficiently, whereas increased the intermolecular hydrogen bondings between DMF and trehalose. Thus, the origin of its denaturing effects of DMF on protein is thought to be due to the preferential exclusion of trehalose as well as the intermolecular hydrogen bondings between trehalose and DMF. These findings suggest that trehalose protect the CRL protein from DMF-induced unfolding via both indirect and direct interactions.

  2. 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.

  3. Counteracting the climate effects of volcanic eruptions using short-lived greenhouse gases

    Science.gov (United States)

    Fuglestvedt, Jan S.; Samset, Bjørn H.; Shine, Keith P.

    2014-12-01

    A large volcanic eruption might constitute a climate emergency, significantly altering global temperature and precipitation for several years. Major future eruptions will occur, but their size or timing cannot be predicted. We show, for the first time, that it may be possible to counteract these climate effects through deliberate emissions of short-lived greenhouse gases, dampening the abrupt impact of an eruption. We estimate an emission pathway countering a hypothetical eruption 3 times the size of Mount Pinatubo in 1991. We use a global climate model to evaluate global and regional responses to the eruption, with and without counteremissions. We then raise practical, financial, and ethical questions related to such a strategy. Unlike the more commonly discussed geoengineering to mitigate warming from long-lived greenhouse gases, designed emissions to counter temporary cooling would not have the disadvantage of needing to be sustained over long periods. Nevertheless, implementation would still face significant challenges.

  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. 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

    2015-01-02

    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.

  6. Desalted duck egg white peptides promote calcium uptake by counteracting the adverse effects of phytic acid.

    Science.gov (United States)

    Hou, Tao; Liu, Weiwei; Shi, Wen; Ma, Zhili; He, Hui

    2017-03-15

    The structure of the desalted duck egg white peptides-calcium chelate was characterized by fluorescence spectroscopy, fourier transform infrared spectroscopy, and dynamic light scattering. Characterization results showed structural folding and aggregation of amino acids or oligopeptides during the chelation process. Desalted duck egg white peptides enhanced the calcium uptake in the presence of oxalate, phosphate and zinc ions in Caco-2 monolayers. Animal model indicated that desalted duck egg white peptides effectively enhanced the mineral absorption and counteracted the deleterious effects of phytic acid. These findings suggested that desalted duck egg white peptides might promote calcium uptake in three pathways: 1) desalted duck egg white peptides bind with calcium to form soluble chelate and avoid precipitate; 2) the chelate is absorbed as small peptides by enterocyte; and 3) desalted duck egg white peptides regulate the proliferation and differentiation of enterocytes through the interaction with transient receptor potential vanilloid 6 calcium channel.

  7. Disentangling the counteracting effects of water content and carbon mass on zooplankton growth

    DEFF Research Database (Denmark)

    Mcconville, Kristian; Atkinson, Angus; Fileman, Elaine S.

    2017-01-01

    Zooplankton vary widely in carbon percentage (carbon mass as a percentage of wet mass), but are often described as either gelatinous or non-gelatinous. Here we update datasets of carbon percentage and growth rate to investigate whether carbon percentage is a continuous trait, and whether its...... time series at station L4 off Plymouth, UK. This showed separate biomass peaks for gelatinous and crustacean taxa, however, carbon percentage varied 8-fold within the gelatinous group. Species with high carbon mass had lower carbon percentage, allowing separation of the counteracting effects...... of these two variables on growth rate. Specific growth rates, g (d -1) were negatively related to carbon percentage and carbon mass, even in the gelatinous taxa alone, suggesting that the trend is not driven by a categorical difference between these groups. The addition of carbon percentage doubled...

  8. 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.

  9. Agrin promotes synaptic differentiation by counteracting an inhibitory effect of neurotransmitter.

    Science.gov (United States)

    Misgeld, Thomas; Kummer, Terrance T; Lichtman, Jeff W; Sanes, Joshua R

    2005-08-02

    Synaptic organizing molecules and neurotransmission regulate synapse development. Here, we use the skeletal neuromuscular junction to assess the interdependence of effects evoked by an essential synaptic organizing protein, agrin, and the neuromuscular transmitter, acetylcholine (ACh). Mice lacking agrin fail to maintain neuromuscular junctions, whereas neuromuscular synapses differentiate extensively in the absence of ACh. We now demonstrate that agrin's action in vivo depends critically on cholinergic neurotransmission. Using double-mutant mice, we show that synapses do form in the absence of agrin provided that ACh is also absent. We provide evidence that ACh destabilizes nascent postsynaptic sites, and that one major physiological role of agrin is to counteract this "antisynaptogenic" influence. Similar interactions between neurotransmitters and synaptic organizing molecules may operate at synapses in the central nervous system.

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

    DEFF Research Database (Denmark)

    Hong, J; Chen, L; Jeppesen, P B;

    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....

  11. Therapeutic potential of cannabinoids in counteracting chemotherapy-induced adverse effects: an exploratory review.

    Science.gov (United States)

    Ostadhadi, Sattar; Rahmatollahi, Mahdieh; Dehpour, Ahmad-Reza; Rahimian, Reza

    2015-03-01

    Cannabinoids (the active constituents of Cannabis sativa) and their derivatives have got intense attention during recent years because of their extensive pharmacological properties. Cannabinoids first developed as successful agents for alleviating chemotherapy associated nausea and vomiting. Recent investigations revealed that cannabinoids have a wide range of therapeutic effects such as appetite stimulation, inhibition of nausea and emesis, suppression of chemotherapy or radiotherapy-associated bone loss, chemotherapy-induced nephrotoxicity and cardiotoxicity, pain relief, mood amelioration, and last but not the least relief from insomnia. In this exploratory review, we scrutinize the potential of cannabinoids to counteract chemotherapy-induced side effects. Moreover, some novel and yet important pharmacological aspects of cannabinoids such as antitumoral effects will be discussed.

  12. Extending the GMR Current Measurement Range with a Counteracting Magnetic Field

    Directory of Open Access Journals (Sweden)

    Tin Yan Poon

    2013-06-01

    Full Text Available Traditionally, current transformers are often used for current measurement in low voltage (LV electrical networks. They have a large physical size and are not designed for use with power electronic circuits. Semiconductor-based current sensing devices such as the Hall sensor and Giant Magnetoresistive (GMR sensor are advantageous in terms of small size, high sensitivity, wide frequency range, low power consumption, and relatively low cost. Nevertheless, the operational characteristics of these devices limit their current measurement range. In this paper, a design based on using counteracting magnetic field is introduced for extending the GMR current measurement range from 9 A (unipolar to ±45 A. A prototype has been implemented to verify the design and the linear operation of the circuit is demonstrated by experimental results. A microcontroller unit (MCU is used to provide an automatic scaling function to optimize the performance of the proposed current sensor.

  13. Impulse control in the dorsolateral prefrontal cortex counteracts post-diet weight regain in obesity.

    Science.gov (United States)

    Weygandt, Martin; Mai, Knut; Dommes, Esther; Ritter, Kerstin; Leupelt, Verena; Spranger, Joachim; Haynes, John-Dylan

    2015-04-01

    A variety of studies suggest that efficient treatments to induce short-term dietary success in obesity exist. However, sustained maintenance of reduced weight is rare as a large proportion of patients start to regain weight when treatment is discontinued. Thus, from a clinical perspective, it would be desirable to identify factors that counteract post-diet weight regain across longer time-scales. To address this question, we extended our previous work on neural impulse control mechanisms of short-term dietary success in obesity and now investigated the mechanisms counteracting long-term weight regain after a diet. Specifically, we measured neural impulse control during a delay discounting task with fMRI at two time points, i.e. the beginning ('T0') and the end ('T12') of a one-year follow-up interval after a 12-week diet. Then, we tested whether activity in the dorsolateral prefrontal cortex (DLPFC) at T0 and whether activity changes across the follow-up period (T0-T12) are linked to success in weight maintenance. The analyses conducted show that control-related DLPFC activity at T0 was coupled to the degree of success in weight maintenance. Consistently, also behavioral measures of control were linked to the degree of success in maintenance. A direct comparison of neural and behavioral control parameters for prognostic weight change modeling revealed that neural signals were more informative. Taken together, neural impulse control in the DLPFC measured with fMRI directly after a diet predicts real-world diet success in obese patients across extended time periods. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Arsenic-induced micronuclei formation in mammalian cells and its counteraction by tea.

    Science.gov (United States)

    Sinha, Dona; Roy, Madhumita; Siddiqi, Maqsood; Bhattacharya, Rathin K

    2005-01-01

    The Gangetic plain of West Bengal, India, has been engulfed by a disastrous environmental calamity of arsenic contamination of the ground water. Chronic arsenic toxicity caused by drinking arsenic-contaminated water has been one of the worst health hazards gradually affecting nine districts of West Bengal since the early 1980s. Over and above hyperpigmentation and keratosis,weakness, burning sensation of the eyes, swelling of the legs, liver fibrosis, chronic lung disease, gangrene of the toes, neuropathy, and skin cancer are other manifestations. Induction of cancer is frequently associated with DNA damage, changes in ploidy of cells, and non-random chromosome aberrations. Counteraction of these genotoxic and cytogenetic abnormalities with natural dietary polyphenols could be a useful strategy to combat arsenic-induced DNA damage and thereby cancer. A review of the literature showed that it is the antioxidant property of tea polyphenols that affords protection against various types of cancer. The present study was conducted to investigate whether the extracts of green tea and black tea (Darjeeling and Assam) as well as their polyphenols could ameliorate this arsenic-induced genotoxicity. The normal mammalian cell culture derived from male Chinese hamster lung fibroblast cells (V79) was used as the test system to assess the genotoxicity by micronucleus assay. The results showed that both green tea and black tea extracts have equal potential in modulating the arsenic-induced genotoxicity. This effect was perhaps induced by the constituent polyphenols present in green and black tea. In addition, the repair activity of the damaged cells was enhanced when treated with these tea extracts and their polyphenols. Thus, tea and its polyphenols may have a promising role in counteracting the devastating effects of arsenic.

  15. Improvement of alveolar-capillary membrane diffusing capacity with enalapril in chronic heart failure and counteracting effect of aspirin.

    Science.gov (United States)

    Guazzi, M; Marenzi, G; Alimento, M; Contini, M; Agostoni, P

    1997-04-01

    KII ACE, the enzyme that converts angiotensin I and inactivates bradykinin, is highly concentrated in the lungs; its blockade reduces exposure to angiotensin II and enhances exposure to prostaglandins generated by local kinin hyperconcentration. Our hypothesis is that ACE inhibitors improve pulmonary function in chronic heart failure (CHF) by readjusting lung vessel tone and permeability or alveolar-capillary membrane diffusion. In 16 CHF patients and 16 normal volunteers or mild untreated hypertensives, pulmonary function and exercise tests with respiratory gas analysis were assessed on placebo, enalapril (10 mg BID), enalapril plus aspirin (325 mg/d), or aspirin, in random order and double blind, for 15 days each. In CHF, enalapril increased pulmonary carbon monoxide diffusion (DLCO), oxygen consumption (VO2), and exercise tolerance and reduced the ratio of dead space to tidal volume (VD/VT) and the ventilatory equivalent for carbon dioxide production (VE/VCO2). On enalapril, VO2 (r = .80, P < .0001) and VD/VT (r = -.69, P = .003) changes from placebo correlated with those in DLCO. These effects were inhibited by aspirin and were absent in control subjects. In 8 additional patients, hydralazine-isosorbide dinitrate, as an alternative treatment for reducing pulmonary capillary wedge pressure (PCWP) and increasing exercise capacity, were more effective than enalapril for the PCWP but did not affect DLCO and VE/VCO2; amelioration in VO2 and VD/VT was unrelated to DLCO and was not modified by aspirin. ACE inhibition improved pulmonary diffusion in CHF. Hydralazine-isosorbide dinitrate failed to provide this result. Counteraction by aspirin, a prostaglandin inhibitor, bespeaks prostaglandin participation while on enalapril that might readjust capillary permeability or alveolar-capillary membrane diffusion.

  16. 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

    2011-06-01

    NF-E2-related factor 2 (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. Although 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. Although 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, although 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 show 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 seem to significantly modulate ABP-catalyzing UGT in liver. Thus, CPDT exemplifies a counteracting solution to the dilemma posed by Nrf2.

  17. Exogenous and endogenous ghrelin counteracts GLP-1 action to stimulate cAMP signaling and insulin secretion in islet β-cells.

    Science.gov (United States)

    Damdindorj, Boldbaatar; Dezaki, Katsuya; Kurashina, Tomoyuki; Sone, Hideyuki; Rita, Rauza; Kakei, Masafumi; Yada, Toshihiko

    2012-07-30

    We studied interactive effects of insulinotropic GLP-1 and insulinostatic ghrelin on rat pancreatic islets. GLP-1 potentiated glucose-induced insulin release and cAMP production in isolated islets and [Ca(2+)](i) increases in single β-cells, and these potentiations were attenuated by ghrelin. Ghrelin suppressed [Ca(2+)](i) responses to an adenylate cyclase activator forskolin. Moreover, GLP-1-induced insulin release and cAMP production were markedly enhanced by [D-lys(3)]-GHRP-6, a ghrelin receptor antagonist, in isolated islets. These results indicate that both exogenous and endogenous islet-derived ghrelin counteracts glucose-dependent GLP-1 action to increase cAMP production, [Ca(2+)](i) and insulin release in islet β-cells, positioning ghrelin as a modulator of insulinotropic GLP-1.

  18. The role of physical activity in counteracting age-related sarcopenia and cancer cachexia: A brief literature review

    Directory of Open Access Journals (Sweden)

    Scalabrin Mattia

    2016-01-01

    Full Text Available Muscle tissue plays several important health functions . In addition to the important mechanical functions, it represents the biggest reserve of body proteins and it is also able to produce several myokines that are able to induce important beneficial effects, through the interaction with different organs. The loss of muscle mass has a tremendous impact on health and it is not surprising that a great interest has raised on two degenerative, irreversible and unstoppable conditions known as sarcopenia and cachexia. Sarcopenia, the age-related loss of muscle mass, is not a disease or a syndrome, it is not even a medical sign sometimes. Indeed, a general consensus among scientists does not exist regarding the definition and the identification criteria of this condition. On the other hand, cachexia is a wasting syndrome characterized by an uncontrolled and unstoppable loss of muscle mass, associated with fatigue and weakness. It is often associated with a disease like cancer, AIDS, Chronic Obstructive Pulmonary Disease (COPD, multiple sclerosis, tuberculosis etc. Given the complexity of these muscle conditions and considering that during aging and cancer there is an increased risk of comorbidities, regular physical activity might be a crucial point to be carefully evaluated on a single patient basis. The aim of this review is to highlight the impact on society and the etiology of sarcopenia and cancer cachexia, with particular regard to the role played by physical activity in preventing and counteracting these muscle-wasting conditions, focusing attention also on the limitation factors that must be considered during the prescription of physical activity to sarcopenic and cachectic patients.

  19. Angiotensin II counteracts the effects of cAMP/PKA on NHE3 activity and phosphorylation in proximal tubule cells.

    Science.gov (United States)

    Crajoinas, Renato O; Polidoro, Juliano Z; Carneiro de Morais, Carla P A; Castelo-Branco, Regiane C; Girardi, Adriana C C

    2016-11-01

    Binding of angiotensin II (ANG II) to the AT1 receptor (AT1R) in the proximal tubule stimulates Na(+)/H(+) exchanger isoform 3 (NHE3) activity through multiple signaling pathways. However, the effects of ANG II/AT1R-induced inihibitory G protein (Gi) activation and subsequent decrease in cAMP accumulation on NHE3 regulation are not well established. We therefore tested the hypothesis that ANG II reduces cAMP/PKA-mediated phosphorylation of NHE3 on serine 552 and, in doing so, stimulates NHE3 activity. Under basal conditions, ANG II stimulated NHE3 activity but did not affect PKA-mediated NHE3 phosphorylation at serine 552 in opossum kidney (OKP) cells. However, in the presence of the cAMP-elevating agent forskolin (FSK), ANG II blocked FSK-induced NHE3 inhibition, reduced intracellular cAMP concentrations, lowered PKA activity, and prevented the FSK-mediated increase in NHE3 serine 552 phosphorylation. All effects of ANG II were blocked by pretreating OKP cells with the AT1R antagonist losartan, highlighting the contribution of the AT1R/Gi pathway in ANG II-mediated NHE3 upregulation under cAMP-elevating conditions. Accordingly, Gi inhibition by pertussis toxin treatment decreased NHE3 activity both in vitro and in vivo and, more importantly, prevented the stimulatory effect of ANG II on NHE3 activity in rat proximal tubules. Collectively, our results suggest that ANG II counteracts the effects of cAMP/PKA on NHE3 phosphorylation and inhibition by activating the AT1R/Gi pathway. Moreover, these findings support the notion that NHE3 dephosphorylation at serine 552 may represent a key event in the regulation of renal proximal tubule sodium handling by ANG II in the presence of natriuretic hormones that promote cAMP accumulation and transporter phosphorylation.

  20. 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

  1. Ultra-small lipid nanoparticles promote the penetration of coenzyme Q10 in skin cells and counteract oxidative stress.

    Science.gov (United States)

    Lohan, Silke B; Bauersachs, Sonja; Ahlberg, Sebastian; Baisaeng, Nuttakorn; Keck, Cornelia M; Müller, Rainer H; Witte, Ellen; Wolk, Kerstin; Hackbarth, Steffen; Röder, Beate; Lademann, Jürgen; Meinke, Martina C

    2015-01-01

    UV irradiation leads to the formation of reactive oxygen species (ROS). An imbalance between the antioxidant system and ROS can lead to cell damage, premature skin aging or skin cancer. To counteract these processes, antioxidants such as coenzyme Q10 (CoQ10) are contained in many cosmetics. To improve and optimize cell/tissue penetration properties of the lipophilic CoQ10, ultra-small lipid nanoparticles (usNLC) were developed. The antioxidant effectiveness of CoQ10-loaded usNLC compared to conventional nanocarriers was investigated in the human keratinocyte cell line HaCaT. Using confocal laser scanning microscopy investigations of the carriers additionally loaded with nile red showed a clear uptake into cells and their distribution within the cytoplasm. By use of the XTT cell viability test, CoQ10 concentrations of 10-50 μg/ml were shown to be non-toxic, and the antioxidant potential of 10 μg/ml CoQ10 loaded usNLC in the HaCaT cells was analyzed via electron paramagnetic resonance spectroscopy after cellular exposure to UVA (1J/cm(2)) and UVB (18 mJ/cm(2)) irradiation. In comparison with the CoQ10-loaded conventional carriers, usNLC-CoQ10 demonstrated the strongest reduction of the radical formation; reaching up to 23% compared to control cells without nanocarrier treatment. Therefore, usNLC-CoQ10 are very suitable to increase the antioxidant potential of skin.

  2. Increase of productivity attacks of young basketbal players on the basis perfection their competitive activity.

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    Kozin V.V.

    2011-02-01

    Full Text Available Research objective is increase of productivity attacks of basketball players 15-17 years on the basis perfection their competitive activity creation of situations of counteractions is carried out by connection of models in the directed programming system of game activity. The system has different character and allows to model individual and group counteractions. The gain of indicators of mental qualities is as a result established, increase of indicators of force and speed qualities, productivity of attacking actions is noted.

  3. Dynein, Lis1 and CLIP-170 counteract Eg5-dependent centrosome separation during bipolar spindle assembly.

    Science.gov (United States)

    Tanenbaum, Marvin E; Macůrek, Libor; Galjart, Niels; Medema, René H

    2008-12-17

    Bipolar spindle assembly critically depends on the microtubule plus-end-directed motor Eg5 that binds antiparallel microtubules and slides them in opposite directions. As such, Eg5 can produce the necessary outward force within the spindle that drives centrosome separation and inhibition of this antiparallel sliding activity results in the formation of monopolar spindles. Here, we show that upon depletion of the minus-end-directed motor dynein, or the dynein-binding protein Lis1, bipolar spindles can form in human cells with substantially less Eg5 activity, suggesting that dynein and Lis1 produce an inward force that counteracts the Eg5-dependent outward force. Interestingly, we also observe restoration of spindle bipolarity upon depletion of the microtubule plus-end-tracking protein CLIP-170. This function of CLIP-170 in spindle bipolarity seems to be mediated through its interaction with dynein, as loss of CLIP-115, a highly homologous protein that lacks the dynein-dynactin interaction domain, does not restore spindle bipolarity. Taken together, these results suggest that complexes of dynein, Lis1 and CLIP-170 crosslink and slide microtubules within the spindle, thereby producing an inward force that pulls centrosomes together.

  4. RA-RAR-β counteracts myelin-dependent inhibition of neurite outgrowth via Lingo-1 repression.

    Science.gov (United States)

    Puttagunta, Radhika; Schmandke, André; Floriddia, Elisa; Gaub, Perrine; Fomin, Natalie; Ghyselinck, Norbert B; Di Giovanni, Simone

    2011-06-27

    After an acute central nervous system injury, axonal regeneration is limited as the result of a lack of neuronal intrinsic competence and the presence of extrinsic inhibitory signals. The injury fragments the myelin neuronal insulating layer, releasing extrinsic inhibitory molecules to signal through the neuronal membrane-bound Nogo receptor (NgR) complex. In this paper, we show that a neuronal transcriptional pathway can interfere with extrinsic inhibitory myelin-dependent signaling, thereby promoting neurite outgrowth. Specifically, retinoic acid (RA), acting through the RA receptor β (RAR-β), inhibited myelin-activated NgR signaling through the transcriptional repression of the NgR complex member Lingo-1. We show that suppression of Lingo-1 was required for RA-RAR-β to counteract extrinsic inhibition of neurite outgrowth. Furthermore, we confirm in vivo that RA treatment after a dorsal column overhemisection injury inhibited Lingo-1 expression, specifically through RAR-β. Our findings identify a novel link between RA-RAR-β-dependent proaxonal outgrowth and inhibitory NgR complex-dependent signaling, potentially allowing for the development of molecular strategies to enhance axonal regeneration after a central nervous system injury.

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

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    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.

  6. 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.

  7. 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.

  8. 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.

  9. Counteracting Activities of OCT4 and KLF4 during Reprogramming to Pluripotency

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    Ulf Tiemann

    2014-03-01

    Full Text Available Differentiated cells can be reprogrammed into induced pluripotent stem cells (iPSCs after overexpressing four transcription factors, of which Oct4 is essential. To elucidate the role of Oct4 during reprogramming, we investigated the immediate transcriptional response to inducible Oct4 overexpression in various somatic murine cell types using microarray analysis. By downregulating somatic-specific genes, Oct4 induction influenced each transcriptional program in a unique manner. A significant upregulation of pluripotent markers could not be detected. Therefore, OCT4 facilitates reprogramming by interfering with the somatic transcriptional network rather than by directly initiating a pluripotent gene-expression program. Finally, Oct4 overexpression upregulated the gene Mgarp in all the analyzed cell types. Strikingly, Mgarp expression decreases during the first steps of reprogramming due to a KLF4-dependent inhibition. At later stages, OCT4 counteracts the repressive activity of KLF4, thereby enhancing Mgarp expression. We show that this temporal expression pattern is crucial for the efficient generation of iPSCs.

  10. Magnetite nanoparticles induced adaptive mechanisms counteract cell death in human pulmonary fibroblasts.

    Science.gov (United States)

    Radu, Mihaela; Dinu, Diana; Sima, Cornelia; Burlacu, Radu; Hermenean, Anca; Ardelean, Aurel; Dinischiotu, Anca

    2015-10-01

    Magnetite nanoparticles (MNP) have attracted great interest for biomedical applications due to their unique chemical and physical properties, but the MNP impact on human health is not fully known. Consequently, our study proposes to highlight the biochemical mechanisms that underline the toxic effects of MNP on a human lung fibroblast cell line (MRC-5). The cytotoxicity generated by MNP in MRC-5 cells was dose and time-dependent. MNP-treated MRC-5 cells accumulated large amount of iron and reactive oxygen species (ROS) and exhibited elevated antioxidant scavenger enzymes. Reduced glutathione (GSH) depletion and enhanced lipid peroxidation (LPO) processes were also observed. The cellular capacity to counteract the oxidative damage was sustained by high levels of heat shock protein 60 (Hsp60), a protein that confers resistance against ROS attack and inhibition of cell death. While significant augmentations in nitric oxide (NO) and prostaglandine E2 (PGE2) levels were detected after 72 h of MNP-exposure only, caspase-1 was activated earlier starting with 24h post-treatment. Taken together, our results suggest that MRC-5 cells have the capacity to develop cell protection mechanisms against MNP. Detailed knowledge of the mechanisms induced by MNP in cell culture could be essential for their prospective use in various in vivo biochemical applications.

  11. 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.

  12. Counteracting geometrical attacks on robust image watermarking by constructing a deformable pyramid transform

    Science.gov (United States)

    Wang, Chuntao; Ni, Jiangqun; Zhang, Dong

    2013-12-01

    Counteracting geometrical attacks remains one of the most challenging problems in robust watermarking. In this paper, we resist rotation, scaling, and translation (RST) by constructing a kind of deformable pyramid transform (DPT) that is shift-invariant, steerable, and scalable. The DPT is extended from a closed-form polar-separable steerable pyramid transform (SPT). The radial component of the SPT's basis filters is taken as the kernel of the scalable basis filters, and the angular component is used for the steerable basis filters. The shift-invariance is inherited from the SPT by retaining undecimated high-pass and band-pass subbands. Based on the designed DPT, we theoretically derive interpolation functions for steerability and scalability and synchronization mechanisms for translation, rotation, and scaling. By exploiting the preferable characteristics of DPT, we develop a new template-based robust image watermarking scheme that is resilient to RST. Translation invariance is achieved by taking the Fourier magnitude of the cover image as the DPT's input. The resilience to rotation and scaling is obtained using the synchronization mechanisms for rotation and scaling, for which an efficient template-matching algorithm has been devised. Extensive simulations show that the proposed scheme is highly robust to geometrical attacks, such as RST, cropping, and row/column line removal, as well as common signal processing attacks such as JPEG compression, additive white Gaussian noise, and median filtering.

  13. P-cadherin counteracts myosin II-B function: implications in melanoma progression

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    De Wever Olivier

    2010-09-01

    Full Text Available Abstract Background Malignant transformation of melanocytes is frequently attended by a switch in cadherin expression profile as shown for E- and N-cadherin. For P-cadherin, downregulation in metastasizing melanoma has been demonstrated, and over-expression of P-cadherin in melanoma cell lines has been shown to inhibit invasion. The strong invasive and metastatic nature of cutaneous melanoma implies a deregulated interplay between intercellular adhesion and migration-related molecules Results In this study we performed a microarray analysis to compare the mRNA expression profile of an invasive BLM melanoma cell line (BLM LIE and the non-invasive P-cadherin over-expression variant (BLM P-cad. Results indicate that nonmuscle myosin II-B is downregulated in BLM P-cad. Moreover, myosin II-B plays a major role in melanoma migration and invasiveness by retracting the tail during the migratory cycle, as shown by the localization of myosin II-B stress fibers relative to Golgi and the higher levels of phosphorylated myosin light chain. Analysis of P-cadherin and myosin II-B in nodular melanoma sections and in a panel of melanoma cell lines further confirmed that there is an inverse relationship between both molecules. Conclusions Therefore, we conclude that P-cadherin counteracts the expression and function of myosin II-B, resulting in the suppression of the invasive and migratory behaviour of BLM melanoma cells

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

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    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.

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

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    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.

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

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    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.

  17. Midazolam 12 mg is moderately counteracted by 250 mg caffeine in man.

    Science.gov (United States)

    Mattila, M J; Vainio, P; Nurminen, M L; Vanakoski, J; Seppälä, T

    2000-12-01

    Caffeine (Caf) counteracts various effects of benzodiazepines (BZDs). Since the effects of zolpidem, a short-acting atypical GABA(A)-BZD agonist, were not antagonized by Caf, we studied an interaction between Caf and midazolam (Mid) in healthy volunteers. In Study 1, 108 healthy students divided to 6 parallel groups were given Mid 12 mg (capsule) and Caf 125 and 250 mg (in decaffeinated coffee), alone and in combinations in the double-blind placebo-controlled manner. Objective and subjective tests were done before and at 45 and 90 min after intake. Ranked delta-values (changes from baseline) were analyzed by one-way contrast ANOVA and Scheffe's tests. In Study 2, six healthy subjects took Mid 15 mg (tablet) with and without Caf 300 mg. The dynamic effects were analyzed as in Study 1 and the plasma concentrations were assayed. In Study 1, learn effects after placebo (ad + 15%) were seen for letter cancellation and digit symbol substitution tests. Midazolam alone significantly (p 0.05). In conclusion, in a parallel group study, sedative effects of Mid 12 mg were only moderately antagonized by Caf 250 mg but not by Caf 125 mg. In a cross-over study, a weak interaction was found subjectively but not in objective measures.

  18. 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.

  19. MiR-298 Counteracts Mutant Androgen Receptor Toxicity in Spinal and Bulbar Muscular Atrophy.

    Science.gov (United States)

    Pourshafie, Naemeh; Lee, Philip R; Chen, Ke-Lian; Harmison, George G; Bott, Laura C; Katsuno, Masahisa; Sobue, Gen; Burnett, Barrington G; Fischbeck, Kenneth H; Rinaldi, Carlo

    2016-05-01

    Spinal and bulbar muscular atrophy (SBMA) is a currently untreatable adult-onset neuromuscular disease caused by expansion of a polyglutamine repeat in the androgen receptor (AR). In SBMA, as in other polyglutamine diseases, a toxic gain of function in the mutant protein is an important factor in the disease mechanism; therefore, reducing the mutant protein holds promise as an effective treatment strategy. In this work, we evaluated a microRNA (miRNA) to reduce AR expression. From a list of predicted miRNAs that target human AR, we selected microRNA-298 (miR-298) for its ability to downregulate AR mRNA and protein levels when transfected in cells overexpressing wild-type and mutant AR and in SBMA patient-derived fibroblasts. We showed that miR-298 directly binds to the 3'-untranslated region of the human AR transcript, and counteracts AR toxicity in vitro. Intravenous delivery of miR-298 with adeno-associated virus serotype 9 vector resulted in efficient transduction of muscle and spinal cord and amelioration of the disease phenotype in SBMA mice. Our findings support the development of miRNAs as a therapeutic strategy for SBMA and other neurodegenerative disorders caused by toxic proteins.

  20. Thermal analysis on the EAST tungsten plasma facing components with shaping structure counteracting the misalignment issues

    Science.gov (United States)

    Baoguo, Wang; Dahuan, Zhu; Rui, Ding; Junling, Chen

    2017-02-01

    Tungsten monoblock type tiles with ITER dimensions along with supporting cassette components were installed at EAST’s upper diverter during 2014 and EAST’s lower diverter will also be upgraded in the future. These cassette structures pose critical issues on the high cumulative incident heat flux due to the leading edges and misalignments (0 ˜ 1.5 mm), which may result in the destruction or even melting of the tungsten tile. The present work summarizes the thermal analysis using ANSYS multiphysics software 15.0 performed on the actively cooled W tiles to evaluate the shaping effect on surface temperature. In the current heat flux conditions (Q|| ˜ 100 MW m-2), the adopted chamfer shaping (1 × 1 mm) can only reduce the maximum temperature by about 14%, but it also has a melting risk at the maximum misalignment of 1.5 mm. The candidate shaping solutions elliptical (round) edge, dome and fish-scale are analyzed for comparison and are identified not as good as the dual chamfer structure. A relatively good dual chamfer (2 × 13 mm) shaping forming a symmetrical sloping roof structure can effectively counteract the 1.5 mm misalignment, reducing the maximum temperature by up to 50%. However, in the future heat flux conditions (Q|| ˜ 287 MW m-2), it may only endure about 0.5 mm misalignment. Moreover, no proper shaping solution has been found that can avoid melting at the maximum misalignment of 1.5 mm. Thus, the engineering misalignment has to be limited to an acceptable level. Supported by the National Magnetic Confinement Fusion Science Program of China (Nos. 2013GB107004 and 2013GB105003) and National Natural Science Foundation of China (No. 11405209).

  1. Definition of singularity due to Newton’s second law counteracting gravity

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    Arezu Jahanshir

    2013-03-01

    Full Text Available With several issuesbeing raised in the late twentieth century, modern physics was challenged andwhile quantum mechanics and relativity did not have the ability to respond andresolve issues also they cannot do it todays.Despite such problems, physicists are trying to find an appropriate andconvincing response only on the scope of quantum physics and relativity and inthis respect need topay attention to the classical mechanics.Series of failures exist in some categories of these theories, that prior totheir use, they should be clarified and resolved. Regarding on review of Newton's second law in this paper, we have been attempted toenter to the sub-quantum space by crossing the border of quantum mechanics thento survey of counteracting Newton's second law and the universal gravitationlaw and finally we can be analyzed and investigated the results. Insub-quantum space, we passed across the black hole and reach the formation ofthe absolute black hole (a new term that has been presented for the first time in astrophysics by the authors by specifying the limits of Newton's second lawand gravitation law, then the singularity will be explained in the explosion of an absolute black hole. In thisreview we will be forced to change their attitude towards the singularity andthe general conclusion in the singularity state is: volume will not be zero, densitywill be limited, the time is not a physical quantity (absolute or relative anda human as an observer (who is not neutral has invented the time just forusing it to the explain the ticking clock. We use the time just for the clockticking and in different physical situations we can only examine the working of the clocks or compare them to each other.

  2. A type IV translocated Legionella cysteine phytase counteracts intracellular growth restriction by phytate.

    Science.gov (United States)

    Weber, Stephen; Stirnimann, Christian U; Wieser, Mara; Frey, Daniel; Meier, Roger; Engelhardt, Sabrina; Li, Xiaodan; Capitani, Guido; Kammerer, Richard A; Hilbi, Hubert

    2014-12-05

    The causative agent of Legionnaires' pneumonia, Legionella pneumophila, colonizes diverse environmental niches, including biofilms, plant material, and protozoa. In these habitats, myo-inositol hexakisphosphate (phytate) is prevalent and used as a phosphate storage compound or as a siderophore. L. pneumophila replicates in protozoa and mammalian phagocytes within a unique "Legionella-containing vacuole." The bacteria govern host cell interactions through the Icm/Dot type IV secretion system (T4SS) and ∼300 different "effector" proteins. Here we characterize a hitherto unrecognized Icm/Dot substrate, LppA, as a phytate phosphatase (phytase). Phytase activity of recombinant LppA required catalytically essential cysteine (Cys(231)) and arginine (Arg(237)) residues. The structure of LppA at 1.4 Å resolution revealed a mainly α-helical globular protein stabilized by four antiparallel β-sheets that binds two phosphate moieties. The phosphates localize to a P-loop active site characteristic of dual specificity phosphatases or to a non-catalytic site, respectively. Phytate reversibly abolished growth of L. pneumophila in broth, and growth inhibition was relieved by overproduction of LppA or by metal ion titration. L. pneumophila lacking lppA replicated less efficiently in phytate-loaded Acanthamoeba castellanii or Dictyostelium discoideum, and the intracellular growth defect was complemented by the phytase gene. These findings identify the chelator phytate as an intracellular bacteriostatic component of cell-autonomous host immunity and reveal a T4SS-translocated L. pneumophila phytase that counteracts intracellular bacterial growth restriction by phytate. Thus, bacterial phytases might represent therapeutic targets to combat intracellular pathogens.

  3. Sulforaphane counteracts aggressiveness of pancreatic cancer driven by dysregulated Cx43-mediated gap junctional intercellular communication

    Science.gov (United States)

    Zhang, Yiyao; Isayev, Orkhan; Heilmann, Katharina; Schoensiegel, Frank; Liu, Li; Nessling, Michelle; Richter, Karsten; Labsch, Sabrina; Nwaeburu, Clifford C.; Mattern, Juergen; Gladkich, Jury; Giese, Nathalia; Werner, Jens; Schemmer, Peter; Gross, Wolfgang; Gebhard, Martha M.; Gerhauser, Clarissa; Schaefer, Michael; Herr, Ingrid

    2014-01-01

    The extreme aggressiveness of pancreatic ductal adenocarcinoma (PDA) has been associated with blocked gap junctional intercellular communication (GJIC) and the presence of cancer stem cells (CSCs). We examined whether disturbed GJIC is responsible for a CSC phenotype in established and primary cancer cells and patient tissue of PDA using interdisciplinary methods based in physiology, cell and molecular biology, histology and epigenetics. Flux of fluorescent dyes and gemcitabine through gap junctions (GJs) was intact in less aggressive cells but not in highly malignant cells with morphological dysfunctional GJs. Among several connexins, only Cx43 was expressed on the cell surface of less aggressive and GJIC-competent cells, whereas Cx43 surface expression was absent in highly malignant, E-cadherin-negative and GJIC-incompetent cells. The levels of total Cx43 protein and Cx43 phosphorylated at Ser368 and Ser279/282 were high in normal tissue but low to absent in malignant tissue. si-RNA-mediated inhibition of Cx43 expression in GJIC-competent cells prevented GJIC and induced colony formation and the expression of stem cell-related factors. The bioactive substance sulforaphane enhanced Cx43 and E-cadherin levels, inhibited the CSC markers c-Met and CD133, improved the functional morphology of GJs and enhanced GJIC. Sulforaphane altered the phosphorylation of several kinases and their substrates and inhibition of GSK3, JNK and PKC prevented sulforaphane-induced CX43 expression. The sulforaphane-mediated expression of Cx43 was not correlated with enhanced Cx43 RNA expression, acetylated histone binding and Cx43 promoter de-methylation, suggesting that posttranslational phosphorylation is the dominant regulatory mechanism. Together, the absence of Cx43 prevents GJIC and enhances aggressiveness, whereas sulforaphane counteracts this process, and our findings highlight dietary co-treatment as a viable treatment option for PDA. PMID:24742583

  4. S100b Counteracts Neurodegeneration of Rat Cholinergic Neurons in Brain Slices after Oxygen-Glucose Deprivation

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    Daniela Serbinek

    2010-01-01

    Full Text Available Alzheimer's disease is a severe chronic neurodegenerative disorder characterized by beta-amyloid plaques, tau pathology, cerebrovascular damage, inflammation, reactive gliosis, and cell death of cholinergic neurons. The aim of the present study is to test whether the glia-derived molecule S100b can counteract neurodegeneration of cholinergic neurons after oxygen-glucose deprivation (OGD in organotypic brain slices of basal nucleus of Meynert. Our data showed that 3 days of OGD induced a marked decrease of cholinergic neurons (60% of control, which could be counteracted by 50 μg/mL recombinant S100b. The effect was dose and time dependent. Application of nerve growth factor or fibroblast growth factor-2 was less protective. C-fos-like immunoreactivity was enhanced 3 hours after OGD indicating metabolic stress. We conclude that S100b is a potent neuroprotective factor for cholinergic neurons during ischemic events.

  5. 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

  6. Success counteracting tobacco company interference in Thailand: an example of FCTC implementation for low- and middle-income countries.

    Science.gov (United States)

    Charoenca, Naowarut; Mock, Jeremiah; Kungskulniti, Nipapun; Preechawong, Sunida; Kojetin, Nicholas; Hamann, Stephen L

    2012-04-01

    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 that tobacco control

  7. The Older Woman: Increased Psychosocial Benefits from Physical Activity.

    Science.gov (United States)

    Wakat, Diane; Odom, Sarah

    1982-01-01

    Older women who participate in physical activity programs find physical benefits in the improvement of cardiovascular and musculoskeletal systems. The psychosocial benefits which result from physical activity include an increase in self-esteem, increased social contacts, a counteraction to depression, and improved stress management. Suggestions…

  8. Adaptive brain shut-down counteracts neuroinflammation in the near-term ovine fetus

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    Alex eXU

    2014-06-01

    Full Text Available Objective: Repetitive umbilical cord occlusions (UCOs in ovine fetus leading to severe acidemia result in adaptive shut-down of electrocortical activity (ECOG as well as systemic and brain inflammation. We hypothesized that the fetuses with earlier ECOG shut-down as a neuroprotective mechanism in response to repetitive UCOs will show less brain inflammation and, moreover, that chronic hypoxia will impact this relationship.Methods: Near term fetal sheep were chronically instrumented with ECOG leads, vascular catheters and a cord occluder and then underwent repetitive UCOs for up to 4 hours or until fetal arterial pH was < 7.00. Eight animals, hypoxic prior to the UCOs (SaO2< 55%, were allowed to recover 24 hours post insult, while 14 animals, five of whom also were chronically hypoxic, were allowed to recover 48 hours post insult, after which brains were perfusion-fixed. Time of ECOG shut-down and corresponding pH were noted, as well as time to then reach pH<7.00 (ΔT. Microglia (MG were counted as a measure of inflammation in grey matter layers 4-6 (GM4-6 where most ECOG activity is generated. Results are reported as mean±SEM for p<0.05.Results: Repetitive UCOs resulted in worsening acidosis over 3 to 4 hours with arterial pH decreasing to 6.97±0.02 all UCO groups’ animals, recovering to baseline by 24 hours. ECOG shut-down occurred 52±7 min before reaching pH < 7.00 at pH 7.23±0.02 across the animal groups. MG counts were inversely correlated to ΔT in 24 hours recovery animals (R=-0.84, as expected. This was not the case in normoxic 48 hours recovery animals, and, surprisingly, in hypoxic 48 hours recovery animals this relationship was reversed (R=0.90.Conclusion: Adaptive brain shut-down during labour-like worsening acidemia counteracts neuroinflammation in a hypoxia- and time-dependent manner.

  9. 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

  10. rgs-CaM Detects and Counteracts Viral RNA Silencing Suppressors in Plant Immune Priming.

    Science.gov (United States)

    Jeon, Eun Jin; Tadamura, Kazuki; Murakami, Taiki; Inaba, Jun-Ichi; Kim, Bo Min; Sato, Masako; Atsumi, Go; Kuchitsu, Kazuyuki; Masuta, Chikara; Nakahara, Kenji S

    2017-10-01

    -plant resistance against secondary infection with pathogens; this so-called systemic acquired resistance (SAR) has been known for more than half a century and continues to be extensively studied. SAR-induced plants strongly and rapidly express a number of antibiotics and pathogenesis-related proteins targeted against secondary infection, which can account for enhanced resistance against bacterial and fungal pathogens but are not thought to control viral infection. This study showed that enhanced resistance against cucumber mosaic virus is caused by a tobacco calmodulin-like protein, rgs-CaM, which detects and counteracts the major viral virulence factor (RNA silencing suppressor) after SAR induction. rgs-CaM-mediated SAR illustrates the growth versus defense trade-off in plants, as it targets the major virulence factor only under specific biotic stress conditions, thus avoiding the cost of constitutive activation while reducing the damage from virus infection. Copyright © 2017 American Society for Microbiology.

  11. Methylene blue counteracts H2S toxicity-induced cardiac depression by restoring L-type Ca channel activity

    Science.gov (United States)

    Zhang, Xue-Qian; Sonobe, Takashi; Song, Jianliang; Rannals, Matthew D.; Wang, JuFang; Tubbs, Nicole; Cheung, Joseph Y.; Haouzi, Philippe

    2016-01-01

    We have previously reported that methylene blue (MB) can counteract hydrogen sulfide (H2S) intoxication-induced circulatory failure. Because of the multifarious effects of high concentrations of H2S on cardiac function, as well as the numerous properties of MB, the nature of this interaction, if any, remains uncertain. The aim of this study was to clarify 1) the effects of MB on H2S-induced cardiac toxicity and 2) whether L-type Ca2+ channels, one of the targets of H2S, could transduce some of the counteracting effects of MB. In sedated rats, H2S infused at a rate that would be lethal within 5 min (24 μM·kg−1·min−1), produced a rapid fall in left ventricle ejection fraction, determined by echocardiography, leading to a pulseless electrical activity. Blood concentrations of gaseous H2S reached 7.09 ± 3.53 μM when cardiac contractility started to decrease. Two to three injections of MB (4 mg/kg) transiently restored cardiac contractility, blood pressure, and V̇o2, allowing the animals to stay alive until the end of H2S infusion. MB also delayed PEA by several minutes following H2S-induced coma and shock in unsedated rats. Applying a solution containing lethal levels of H2S (100 μM) on isolated mouse cardiomyocytes significantly reduced cell contractility, intracellular calcium concentration ([Ca2+]i) transient amplitudes, and L-type Ca2+ currents (ICa) within 3 min of exposure. MB (20 mg/l) restored the cardiomyocyte function, ([Ca2+]i) transient, and ICa. The present results offer a new approach for counteracting H2S toxicity and potentially other conditions associated with acute inhibition of L-type Ca2+ channels. PMID:26962024

  12. Methylene blue counteracts H2S toxicity-induced cardiac depression by restoring L-type Ca channel activity.

    Science.gov (United States)

    Judenherc-Haouzi, Annick; Zhang, Xue-Qian; Sonobe, Takashi; Song, Jianliang; Rannals, Matthew D; Wang, JuFang; Tubbs, Nicole; Cheung, Joseph Y; Haouzi, Philippe

    2016-06-01

    We have previously reported that methylene blue (MB) can counteract hydrogen sulfide (H2S) intoxication-induced circulatory failure. Because of the multifarious effects of high concentrations of H2S on cardiac function, as well as the numerous properties of MB, the nature of this interaction, if any, remains uncertain. The aim of this study was to clarify 1) the effects of MB on H2S-induced cardiac toxicity and 2) whether L-type Ca(2+) channels, one of the targets of H2S, could transduce some of the counteracting effects of MB. In sedated rats, H2S infused at a rate that would be lethal within 5 min (24 μM·kg(-1)·min(-1)), produced a rapid fall in left ventricle ejection fraction, determined by echocardiography, leading to a pulseless electrical activity. Blood concentrations of gaseous H2S reached 7.09 ± 3.53 μM when cardiac contractility started to decrease. Two to three injections of MB (4 mg/kg) transiently restored cardiac contractility, blood pressure, and V̇o2, allowing the animals to stay alive until the end of H2S infusion. MB also delayed PEA by several minutes following H2S-induced coma and shock in unsedated rats. Applying a solution containing lethal levels of H2S (100 μM) on isolated mouse cardiomyocytes significantly reduced cell contractility, intracellular calcium concentration ([Ca(2+)]i) transient amplitudes, and L-type Ca(2+) currents (ICa) within 3 min of exposure. MB (20 mg/l) restored the cardiomyocyte function, ([Ca(2+)]i) transient, and ICa The present results offer a new approach for counteracting H2S toxicity and potentially other conditions associated with acute inhibition of L-type Ca(2+) channels. Copyright © 2016 the American Physiological Society.

  13. 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.

  14. An Anti-apoE4 Specific Monoclonal Antibody Counteracts the Pathological Effects of apoE4 In Vivo.

    Science.gov (United States)

    Luz, Ishai; Liraz, Ori; Michaelson, Daniel M

    2016-06-02

    ApolipoproteinE4 (apoE4) is the most prevalent genetic risk factor for Alzheimer's disease (AD) and as such is a promising therapeutic target. This study examined the extent to which the pathological effects of apoE4 can be counteracted in vivo utilizing an immunological approach in which anti-apoE4 antibodies are applied peripherally by i.p. injections into apoE4-targeted replacement mice. Prerequisites for the successful pursuit of this objective are the availability of antibodies that specifically bind brain apoE4 and not apoE3, and demonstrating that direct application of these antibodies into the brain can counteract the effects of apoE4. Accordingly, it was shown that the antiapoE4 monoclonal antibody (mAb) 9D11 binds specifically to brain apoE4 and not apoE3. Direct i.c.v. application of mAb 9D11 prevented the apoE4-driven accumulation of Aβ in hippocampal neurons following activation of the amyloid cascade by inhibiting the Aβ-degrading enzyme neprilysin. These findings provide a proof-of-concept that anti-apoE4 mAb 9D11, when introduced into the brain, can counteract the apoE4 effects in vivo. Subsequent experiments, utilizing repeated i.p. injections of mAb 9D11, resulted in the formation of apoE/IgG complexes specifically in apoE4 mice. This was associated with reversal of the cognitive impairments of apoE4 in the Morris water maze and the novel object recognition test as well as with reversal of key apoE4-driven pathologies including the hyperphosphorylated tau and the reduced levels of the apoER2 receptor. These results indicate that anti-apoE4 immunotherapy counteracts the cognitive and brain pathological effects of apoE4, and suggest that such an approach could also benefit human apoE4 carriers.

  15. The novel adipokine progranulin counteracts IL-1 and TLR4-driven inflammatory response in human and murine chondrocytes via TNFR1

    Science.gov (United States)

    Abella, Vanessa; Scotece, Morena; Conde, Javier; López, Verónica; Pirozzi, Claudio; Pino, Jesús; Gómez, Rodolfo; Lago, Francisca; González-Gay, Miguel Ángel; Gualillo, Oreste

    2016-01-01

    Progranulin (PGRN) is a recently identified adipokine that is supposed to have anti-inflammatory actions. The proinflammatory cytokine interleukin-1β (IL1β) stimulates several mediators of cartilage degradation. Toll like receptor-4 (TLR4) can bind to various damage-associated molecular patterns, leading to inflammatory condition. So far, no data exist of PGRN effects in inflammatory conditions induced by IL1β or lipopolysaccharide (LPS). Here, we investigated the anti-inflammatory potential of PGRN in IL1β- or LPS-induced inflammatory responses of chondrocytes. Human osteoarthritic chondrocytes and ATDC-5 cells were treated with PGRN in presence or not of IL1β or LPS. First, we showed that recombinant PGRN had no effects on cell viability. We present evidence that PGRN expression was increased during the differentiation of ATDC-5 cell line. Moreover, PGRN mRNA and protein expression is increased in cartilage, synovial and infrapatellar fat pad tissue samples from OA patients. PGRN mRNA levels are upregulated under TNFα and IL1β stimulation. Our data showed that PGRN is able to significantly counteract the IL1β-induced expression of NOS2, COX2, MMP13 and VCAM-1. LPS-induced expression of NOS2 is also decreased by PGRN. These effects are mediated, at least in part, through TNFR1. Taken together, our results suggest that PGRN has a clear anti-inflammatory function. PMID:26853108

  16. 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.

  17. Melatonin Counteracts at a Transcriptional Level the Inflammatory and Apoptotic Response Secondary to Ischemic Brain Injury Induced by Middle Cerebral Artery Blockade in Aging Rats.

    Science.gov (United States)

    Paredes, Sergio D; Rancan, Lisa; Kireev, Roman; González, Alberto; Louzao, Pedro; González, Pablo; Rodríguez-Bobada, Cruz; García, Cruz; Vara, Elena; Tresguerres, Jesús A F

    2015-01-01

    Aging increases oxidative stress and inflammation. Melatonin counteracts inflammation and apoptosis. This study investigated the possible protective effect of melatonin on the inflammatory and apoptotic response secondary to ischemia induced by blockade of the right middle cerebral artery (MCA) in aging male Wistar rats. Animals were subjected to MCA obstruction. After 24 h or 7 days of procedure, 14-month-old nontreated and treated rats with a daily dose of 10 mg/kg melatonin were sacrificed and right and left hippocampus and cortex were collected. Rats aged 2 and 6 months, respectively, were subjected to the same brain injury protocol, but they were not treated with melatonin. mRNA expression of interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), Bcl-2-associated death promoter (BAD), Bcl-2-associated X protein (BAX), glial fibrillary acidic protein (GFAP), B-cell lymphoma 2 (Bcl-2), and sirtuin 1 was measured by reverse transcription-polymerase chain reaction. In nontreated animals, a significant time-dependent increase in IL-1β, TNF-α, BAD, and BAX was observed in the ischemic area of both hippocampus and cortex, and to a lesser extent in the contralateral hemisphere. Hippocampal GFAP was also significantly elevated, while Bcl-2 and sirtuin 1 decreased significantly in response to ischemia. Aging aggravated these changes. Melatonin administration was able to reverse significantly these alterations. In conclusion, melatonin may ameliorate the age-dependent inflammatory and apoptotic response secondary to ischemic cerebral injury.

  18. Maternal Methyl Donor Supplementation during Gestation Counteracts the Bisphenol A-Induced Impairment of Intestinal Morphology, Disaccharidase Activity, and Nutrient Transporters Gene Expression in Newborn and Weaning Pigs

    Directory of Open Access Journals (Sweden)

    Hong Liu

    2017-04-01

    Full Text Available This study was conducted to explore whether exposure to bisphenol A (BPA during pregnancy could change intestinal digestion and absorption function in offspring using pigs as a model, and whether methyl donor (MET could counteract the BPA-induced impacts. Fifty Landrace × Yorkshire sows were divided into four dietary groups throughout gestation: control diet (CON; control diet supplemented with BPA (50 mg/kg; control diet supplemented with MET (3 g/kg betaine, 400 mg/kg choline, 150 μg/kg vitamin B12, and 15 mg/kg folic acid; and control diet with BPA and MET supplementation (BPA + MET. Intestine samples were collected from pigs’ offspring at birth and weaning. Maternal BPA exposure during pregnancy significantly reduced the ratio of jejunum villus height to crypt depth, decreased the jejunum sucrase activity, down-regulated the mRNA expression of jejunum peptide transporter 1 (Pept1 and DNA methyl transferase 3a (DNMT3a, and decreased the DNA methylation level of jejunum Pept1 in offspring (p < 0.05. Maternal MET supplementation significantly raised the ratio of villus height to crypt depth in jejunum and ileum, improved the jejunum lactase activity, up-regulated the mRNA expression of jejunum Pept1, lactase (LCT, DNMT1, DNMT3a, and methylenetetrahydrofolate reductase (MTHFR, and increased the DNA methylation level of jejunum Pept1 in offspring (p < 0.05. However, the ratio of jejunum villus height to crypt depth was higher in BPA + MET treatment compared with CON and BPA treatment (p < 0.05. Meanwhile, there was no difference in the jejunum sucrase activity, the mRNA expression of jejunum Pept1 and DNMT3a, and the DNA methylation level of jejunum Pept1 between CON and BPA + MET treatment. These results indicated that maternal exposure to BPA during gestation might suppress offspring’s intestinal digestion and absorption function, whereas supplementation of MET could counteract these damages, which might be associated with DNA methylation.

  19. Subthreshold α2-Adrenergic Activation Counteracts Glucagon-Like Peptide-1 Potentiation of Glucose-Stimulated Insulin Secretion

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    Minglin Pan

    2011-01-01

    Full Text Available The pancreatic β cell harbors α2-adrenergic and glucagon-like peptide-1 (GLP-1 receptors on its plasma membrane to sense the corresponding ligands adrenaline/noradrenaline and GLP-1 to govern glucose-stimulated insulin secretion. However, it is not known whether these two signaling systems interact to gain the adequate and timely control of insulin release in response to glucose. The present work shows that the α2-adrenergic agonist clonidine concentration-dependently depresses glucose-stimulated insulin secretion from INS-1 cells. On the contrary, GLP-1 concentration-dependently potentiates insulin secretory response to glucose. Importantly, the present work reveals that subthreshold α2-adrenergic activation with clonidine counteracts GLP-1 potentiation of glucose-induced insulin secretion. This counteractory process relies on pertussis toxin- (PTX- sensitive Gi proteins since it no longer occurs following PTX-mediated inactivation of Gi proteins. The counteraction of GLP-1 potentiation of glucose-stimulated insulin secretion by subthreshold α2-adrenergic activation is likely to serve as a molecular mechanism for the delicate regulation of insulin release.

  20. Confrontation of Major Counteracting Forces in the Globalized Market as a Process of Resolving / Intensifying its Contradictions

    Directory of Open Access Journals (Sweden)

    Deyneka Tetyana A.

    2016-11-01

    Full Text Available The aim of the article is to study the process of resolving/intensifying the contradictions of the contemporary globalized market by means of identifying the counteracting forces that are critical for the period of the formation of post-industrial relations. It is proved that in the context of globalization and gradual establishment of principles of the post-industrial economy, the confrontation of major counteracting market forces is undergoing changes, which is manifested through the processes of resolving/ intensifying the market contradictions. There identified the content of these changes, in particular: if at early stages of the market development the confrontation «state—market» was of decisive importance, at the present time it is the confrontation «civil society – TNCs». There described a multivariate character of the interaction between the major market forces — states, international organizations, TNCs, civil society (both with the effect of achieving community of their interests and with the effect of their disunity. It is proved that the confrontation between the civil society and international corporations objectifies in the globalized economy a new form of contradiction between labor and capital that corresponds to the post-industrial content of economic relations and, in particular the content of property relations

  1. Protective role of malvidin-3-glucoside on peroxynitrite-induced damage in endothelial cells by counteracting reactive species formation and apoptotic mitochondrial pathway.

    Science.gov (United States)

    Paixão, Joana; Dinis, Teresa C P; Almeida, Leonor M

    2012-01-01

    The health-promoted benefits of anthocyanins, including vascular protective effects and antiatherogenic properties, have now been recognized, but the involved molecular mechanisms have not been well elucidated. Following our previous work on cytoprotective mechanisms of some anthocyanins against apoptosis triggered by peroxynitrite in endothelial cells, here we investigated the protective role of malvidin-3-glucoside, a major dietary anthocyanin, on such deleterious process, by exploring the interference on cellular reactive species formation and on apoptotic mitochondrial pathway. Preincubation of cells with 25 μM malvidin-3-glucoside protected efficiently endothelial cells from peroxynitrite-promoted apoptotic death, an effect which may be partially mediated by its ability to decrease the formation of reactive species after cell aggression, as assessed by the dichlorodihydrofluorescein diacetate assay and by carbonyl groups formation. Moreover, malvidin-3-glucoside inhibited mitochondrial apoptotic signaling pathways induced by peroxynitrite, by counteracting mitochondrial membrane depolarization, the activation of caspase-3 and -9, and the increase in the expression of the proapoptotic Bax protein. Altogether, our data expands our knowledge about the molecular mechanisms underlying the vascular protection afforded by malvidin-3-glucoside, and anthocyanins in general, in the context of prevention of endothelial dysfunction and atherosclerosis.

  2. Dopamine D₄ receptor counteracts morphine-induced changes in µ opioid receptor signaling in the striosomes of the rat caudate putamen.

    Science.gov (United States)

    Suárez-Boomgaard, Diana; Gago, Belén; Valderrama-Carvajal, Alejandra; Roales-Buján, Ruth; Van Craenenbroeck, Kathleen; Duchou, Jolien; Borroto-Escuela, Dasiel O; Medina-Luque, José; de la Calle, Adelaida; Fuxe, Kjell; Rivera, Alicia

    2014-01-21

    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.

  3. Neuroinflammatory processes in cognitive disorders: Is there a role for flavonoids and n-3 polyunsaturated fatty acids in counteracting their detrimental effects?

    Science.gov (United States)

    Vauzour, David; Martinsen, Anneloes; Layé, Sophie

    2015-10-01

    Neuroinflammatory processes are known to contribute to the cascade of events culminating in the neuronal damage that underpins neurodegenerative disorders such as Parkinson's and Alzheimer's disease. With the ageing population and increased cases of neurodegenerative diseases, there is a crucial need for the development of new strategies capable to prevent, delay the onset or treat brain dysfunction and associated cognitive decline. Growing evidence sheds light on the use of dietary polyphenols and n-3 long chain polyunsaturated fatty acids to improve cognitive performance and reduce the neuroinflammatory and oxidative stress responses occurring with age and neurodegenerative pathologies. This review will summarise the most recent information related to the impact and mechanisms underlying the neuroinflammatory processes in neurodegenerative disorders. We will also detail the current evidence indicating that flavonoids and n-3 polyunsaturated fatty acids are strong candidates in preventing neuroinflammation and modulating age-related memory decline, and we will describe the potential mechanisms of action underlying their neuroprotective effects. As such, these dietary bioactives represent important precursor molecules in the quest to develop a new generation of drugs capable of counteracting neuroinflammation and neurodegenerative diseases.

  4. 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

  5. Arabidopsis glutamate receptor homolog3.5 modulates cytosolic Ca2+ level to counteract effect of abscisic acid in seed germination.

    Science.gov (United States)

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

    2015-04-01

    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.

  6. Inositol's and other nutraceuticals' synergistic actions counteract insulin resistance in polycystic ovarian syndrome and metabolic syndrome: state-of-the-art and future perspectives.

    Science.gov (United States)

    Paul, Cristiana; Laganà, Antonio Simone; Maniglio, Paolo; Triolo, Onofrio; Brady, David M

    2016-06-01

    The incidence of metabolic syndrome (MetS), type II diabetes (T2D) and polycystic ovarian syndrome (PCOS) has been progressively increasing. Insulin resistance (InsR) seems to play a key role in a majority of phenotypes of these conditions, altering metabolic homeostasis, within muscle, liver, adipose and other tissues. Hyperinsulinemia is often associated with InsR and causes hormonal imbalances especially within ovaries and adrenals. Inositol is a polyalcohol, naturally occurring as nine stereoisomers, including D-chiro-inositol (DCI) and myo-inositol (MI), which have prominent roles in the metabolism of glucose and free fatty acids. MI and DCI have been classified as insulin-sensitizers and seem to adequately counteract several InsR-related metabolic alterations with a safe nutraceutical profile. Based on our analysis of selected studies that investigated MI and/or DCI, we conclude that supplementation with MI and/or DCI complement each other in their metabolic actions and act in synergy with other insulin sensitizing drugs and/or nutraceuticals. Nevertheless, considering the possible severe bias due to different methodologies across published studies, we conclude that there is a need for further studies on larger cohorts and with greater statistical power. These should further clarify outcomes and suitable therapeutic dosages of MI and DCI, possibly based on each patient's clinical status.

  7. 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.

  8. Otters Increasing - Threats Increasing

    Directory of Open Access Journals (Sweden)

    Andreas Kranz

    1994-10-01

    Full Text Available In some parts of Central Europe populations of otters are apparently increasing. Until recently, no research was being conducted on the ecology of otters in mainly artificial habitats like fish farms. Otters are not only a new source of conflict requiring species management, but appear once again threatened by illegal hunting. Austria is dealing with this problem using compensation for otter damage, electric fencing and translocation of problem otters. Despite a rise in illegal killing, Austria does not formally recognise this as a threat.

  9. Modeling reduction of the Urban Heat Island effect to counter-act the effects of climate change in densely built-up areas

    Science.gov (United States)

    Andre, Konrad; Zuvela-Aloise, Maja; Lettmayer, Gudrun; Schwaiger, Hannes Peter; Kaltenegger, Ingrid; Bird, David Neil; Woess-Gallasch, Susanne

    2017-04-01

    The phenomenon of Urban Heat Islands (UHIs) observed in cities, caused by changes in energy balance due to the structural development of the city as well as by sealed surfaces and a lack of vegetation, is expected to strengthen in the future and will further contribute to heat stress, creating an increased need for energy for cooling and ventilation as well as lowering human comfort. Due to a changing climate, rising heat stress, pronounced by an increased intensity or frequency of heat waves, could have far reaching implications for major Austrian cities in the near future. Simultaneous to this expected increasing of the already existing UHI-effect, it is observable, that continuous densification of the core parts of cities is being intensified through implemented traditional urban planning measures. This is particular relevant for high densely populated districts of the city. Several possible counteractions how to address this challenge are already known, partly investigated in urban modeling studies on the effects of modifying the reflective properties of buildings and urban areas for the city of Vienna. On this experience, within the Austrian FFG and KLIEN Smart Cities project JACKY COOL CHECK (Project Nr. 855554), a wide set of measures to reduce heat stress, consisting of e.g. unsealed surfaces, green areas, green roofs, improve reflective properties of different surfaces etc., for the densely built-up residential and business district of Jakomini in the city of Graz/Styria is investigated, to gain decisive data pointing out the peculiarities of UHIs and the potential cooling effects of these target measures for this local specific area. These results serving as a basis for the selection of sustainable measures that will be implemented, in coordination with local stakeholders and considering their interests.

  10. CD55 is a key complement regulatory protein that counteracts complement-mediated inactivation of Newcastle Disease Virus.

    Science.gov (United States)

    Rangaswamy, Udaya S; Cotter, Christopher R; Cheng, Xing; Jin, Hong; Chen, Zhongying

    2016-08-01

    Newcastle disease virus (NDV) is being developed as an oncolytic virus for virotherapy. In this study we analysed the regulation of complement-mediated inactivation of a recombinant NDV in different host cells. NDV grown in human cells was less sensitive to complement-mediated virus inactivation than NDV grown in embryonated chicken eggs. Additionally, NDV produced from HeLa-S3 cells is more resistant to complement than NDV from 293F cells, which correlated with higher expression and incorporation of complement regulatory proteins (CD46, CD55 and CD59) into virions from HeLa-S3 cells. Further analysis of the recombinant NDVs individually expressing the three CD molecules showed that CD55 is the most potent in counteracting complement-mediated virus inactivation. The results provide important information on selecting NDV manufacture substrate to mitigate complement-mediated virus inactivation.

  11. 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

    Antagonists of the N-methyl-D-aspartate (NMDA) receptors such as ketamine, induce abnormalities in healthy subjects similar to those found in schizophrenia. However, recent evidence, suggests that most of the currently known NMDA antagonists have a broader receptor profile than originally thought....... 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...

  12. 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.)

  13. Role of FEN1 S187 phosphorylation in counteracting oxygen-induced stress and regulating postnatal heart development.

    Science.gov (United States)

    Zhou, Lina; Dai, Huifang; Wu, Jian; Zhou, Mian; Yuan, Hua; Du, Juan; Yang, Lu; Wu, Xiwei; Xu, Hong; Hua, Yuejin; Xu, Jian; Zheng, Li; Shen, Binghui

    2017-01-01

    Flap endonuclease 1 (FEN1) phosphorylation is proposed to regulate the action of FEN1 in DNA repair as well as Okazaki fragment maturation. However, the biologic significance of FEN1 phosphorylation in response to DNA damage remains unknown. Here, we report an in vivo role for FEN1 phosphorylation, using a mouse line carrying S187A FEN1, which abolishes FEN1 phosphorylation. Although S187A mouse embryonic fibroblast cells showed normal proliferation under low oxygen levels (2%), the mutant cells accumulated oxidative DNA damage, activated DNA damage checkpoints, and showed G1-phase arrest at atmospheric oxygen levels (21%). This suggests an essential role for FEN1 phosphorylation in repairing oxygen-induced DNA damage and maintaining proper cell cycle progression. Consistently, the mutant cardiomyocytes showed G1-phase arrest due to activation of the p53-mediated DNA damage response at the neonatal stage, which reduces the proliferation potential of the cardiomyocytes and impairs heart development. Nearly 50% of newborns with the S187A mutant died in the first week due to failure to undergo the peroxisome proliferator-activated receptor signaling-dependent switch from glycolysis to fatty acid oxidation. The adult mutant mice developed dilated hearts and showed significantly shorter life spans. Altogether, our results reveal an important role of FEN1 phosphorylation to counteract oxygen-induced stress in the heart during the fetal-to-neonatal transition.-Zhou, L., Dai, H., Wu, J., Zhou, M., Yuan, H., Du, J., Yang, L., Wu, X., Xu, H., Hua, Y., Xu, J., Zheng, L., Shen, B. Role of FEN1 S187 phosphorylation in counteracting oxygen-induced stress and regulating postnatal heart development. © FASEB.

  14. Ash1l methylates Lys36 of histone H3 independently of transcriptional elongation to counteract polycomb silencing.

    Directory of Open Access Journals (Sweden)

    Hitomi Miyazaki

    2013-11-01

    Full Text Available Molecular mechanisms for the establishment of transcriptional memory are poorly understood. 5,6-dichloro-1-D-ribofuranosyl-benzimidazole (DRB is a P-TEFb kinase inhibitor that artificially induces the poised RNA polymerase II (RNAPII, thereby manifesting intermediate steps for the establishment of transcriptional activation. Here, using genetics and DRB, we show that mammalian Absent, small, or homeotic discs 1-like (Ash1l, a member of the trithorax group proteins, methylates Lys36 of histone H3 to promote the establishment of Hox gene expression by counteracting Polycomb silencing. Importantly, we found that Ash1l-dependent Lys36 di-, tri-methylation of histone H3 in a coding region and exclusion of Polycomb group proteins occur independently of transcriptional elongation in embryonic stem (ES cells, although both were previously thought to be consequences of transcription. Genome-wide analyses of histone H3 Lys36 methylation under DRB treatment have suggested that binding of the retinoic acid receptor (RAR to a certain genomic region promotes trimethylation in the RAR-associated gene independent of its ongoing transcription. Moreover, DRB treatment unveils a parallel response between Lys36 methylation of histone H3 and occupancy of either Tip60 or Mof in a region-dependent manner. We also found that Brg1 is another key player involved in the response. Our results uncover a novel regulatory cascade orchestrated by Ash1l with RAR and provide insights into mechanisms underlying the establishment of the transcriptional activation that counteracts Polycomb silencing.

  15. 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

  16. Non-endothelial endothelin counteracts hypoxic vasodilation in porcine large coronary arteries

    DEFF Research Database (Denmark)

    Hedegaard, Elise Røge; Stankevicius, Edgaras; Simonsen, Ulf

    2011-01-01

    of large coronary arteries. RESULTS: In prostaglandin F2α (PGF2α, 10 μM)-contracted segments with endothelium, gradual lowering of oxygen tension from 95 to 1% O2 resulted in vasodilation. The vasodilation to O2 lowering was rightward shifted in segments without endothelium at all O2 concentrations except...... at 1% O2. The endothelin receptor antagonist SB217242 (10 μM) markedly increased hypoxic dilation despite the free tissue ET-1 concentration in the arterial wall was unchanged in 1% O2 versus 95% O2. Exogenous ET-1 reversed hypoxic dilation in segments with and without endothelium, and the hypoxic...... arteries showed an increased sensitivity towards ET-1 compared to the normoxic controls. Without affecting basal NO, hypoxia increased NO concentration in PGF2α-contracted arteries, and an NO synthase inhibitor, L-NOARG,(300 μM, NG-nitro-L-Arginine) reduced hypoxic vasodilation. NO-induced vasodilation...

  17. Low-intensity electrical stimulation counteracts the effects of ovariectomy on bone tissue of rats: effects on bone microarchitecture, viability of osteocytes, and nitric oxide expression.

    Science.gov (United States)

    Lirani-Galvão, A P R; Chavassieux, P; Portero-Muzy, N; Bergamaschi, C T; Silva, O L; Carvalho, A B; Lazaretti-Castro, M; Delmas, P D

    2009-06-01

    Low Intensity Electrical Stimulation (LIES) has been used for bone repair, but little is known about its effects on bone after menopause. Osteocytes probably play a role in mediating this physical stimulus and they could act as transducers through the release of biochemical signals, such as nitric oxide (NO). The aim of the present study was to investigate the effects of LIES on bone structure and remodeling, NOS expression and osteocyte viability in ovariectomized (OVX) rats. Thirty rats (200-220 g) were divided into 3 groups: SHAM, OVX, and OVX subjected to LIES (OVX + LIES) for 12 weeks. Following the protocol, rats were sacrificed and tibias were collected for histomorphometric analysis and immunohistochemical detection of endothelial NO synthase (eNOS), inducible NOS (iNOS), and osteocyte apoptosis (caspase-3 and TUNEL). OVX rats showed significant (p bone volume (10% vs. 25%) and trabecular number (1.7 vs. 3.9), and increased eroded surfaces (4.7% vs. 3.2%) and mineralization surfaces (15.9% vs. 7.7%). In contrast, after LIES, all these parameters were significantly different from OVX but not different from SHAM. eNOS and iNOS were similarly expressed in subperiosteal regions of tibiae cortices of SHAM, not expressed in OVX, and similarly expressed in OVX + LIES when compared to SHAM. In OVX, the percentage of apoptotic osteocytes (24%) was significantly increased when compared to SHAM (11%) and OVX + LIES (8%). Our results suggest that LIES counteracts some effects of OVX on bone tissue preserving bone structure and microarchitecture, iNOS and eNOS expression, and osteocyte viability.

  18. Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain

    Science.gov (United States)

    Rivera, Patricia; Blanco, Eduardo; Bindila, Laura; Alen, Francisco; Vargas, Antonio; Rubio, Leticia; Pavón, Francisco J.; Serrano, Antonia; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence. PMID:26483633

  19. Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain

    Directory of Open Access Journals (Sweden)

    Patricia eRivera

    2015-09-01

    Full Text Available Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10% or sucrose liquid diets for two weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+ and the replicating cell DNA marker 5-bromo-2’-deoxyuridine (BrdU+ in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ, subventricular zone of lateral ventricles (SVZ and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3±1.1 g/kg/day after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ and hypothalamus. The treatments (URB597, ACEA, JWH133 exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence.

  20. 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 (tDCS

  1. Neurophysiological maturation in adolescence – vulnerability and counteracting addiction to alcohol

    Directory of Open Access Journals (Sweden)

    Roman Chwedorowicz

    2017-03-01

    and techniques in developmental and genetic studies of the conditioning of varied vulnerability, and especially increased preferences for alcohol tasting and abuse in adolescence, provide unique possibilities for comprehensive and deepened studies which may contribute to the prevention of alcohol addiction, the genesis of which, to a great extent, is related with the effect of causative environmental and genetic factors during adolescent development.

  2. Diacylglycerol kinase counteracts protein kinase C-mediated inactivation of the EGF receptor

    NARCIS (Netherlands)

    Baal, van J.; Widt, de J.; Divecha, N.; Blitterswijk, van W.J.

    2012-01-01

    Epidermal growth factor receptor (EGFR) activation is negatively regulated by protein kinase C (PKC)signaling. Stimulation of A431 cells with EGF, bradykinin or UTP increased EGFR phosphorylation at Thr654 in a PKC-dependent manner. Inhibition of PKC signaling enhanced EGFR activation, as assessed b

  3. 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.

  4. 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.)

  5. L-theanine partially counteracts caffeine-induced sleep disturbances in rats.

    Science.gov (United States)

    Jang, Hwan-Soo; Jung, Ji Young; Jang, Il-Sung; Jang, Kwang-Ho; Kim, Sang-Hyun; Ha, Jeoung-Hee; Suk, Kyoungho; Lee, Maan-Gee

    2012-04-01

    L-theanine has been reported to inhibit the excitatory effects of caffeine. The present study examined the effects of L-theanine on caffeine-induced sleep disturbances in rats. Rats received the following drug pairings: saline and saline (Control), 7.5 mg/kg caffeine and saline, or 7.5 mg/kg of caffeine followed by various doses of L-theanine (22.5, 37.5, 75, or 150 mg/kg). Vigilance states were divided into: wakefulness (W), transition to slow-wave sleep (tSWS), slow-wave sleep (SWS), and rapid-eye-movement sleep (REMS). Caffeine significantly increased the duration of W and decreased the duration of SWS and REMS compared to the Control. Although L-theanine failed to reverse the caffeine-induced W increase, at 22.5 and 37.5 mg/kg (but not at 75 and 150 mg/kg), it significantly reversed caffeine-induced decreases in SWS. In conclusion, low doses of L-theanine can partially reverse caffeine-induced reductions in SWS; however, effects of L-theanine on caffeine-induced insomnia do not appear to increase dose-dependently.

  6. 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.

  7. 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

    Science.gov (United States)

    Khan, Sheeza; Bano, Zehra; Singh, Laishram R.; Hassan, Md. Imtaiyaz; Islam, Asimul; Ahmad, Faizan

    2013-01-01

    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 (ΔGDo) and functional activity parameters (Km and kcat) 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. PMID:24039776

  8. Toxin-antitoxin loci as stress-response-elements: ChpAK/MazF and ChpBK cleave translated RNAs and are counteracted by tmRNA

    DEFF Research Database (Denmark)

    Christensen, S.K.; Pedersen, K.; Hansen, Flemming G.;

    2003-01-01

    . coli. We show that both proteins inhibit translation by inducing cleavage of translated mRNAs. Consistently, the inhibitory effect of the proteins was counteracted by tmRNA. Amino acid starvation induced strong transcription of chpA that depended on Lon protease but not on ppGpp. Simultaneously, Chp...

  9. Counteracting roles of AMP deaminase and AMP kinase in the development of fatty liver.

    Directory of Open Access Journals (Sweden)

    Miguel A Lanaspa

    Full Text Available Fatty liver (hepatic steatosis is associated with nucleotide turnover, loss of ATP and generation of adenosine monophosphate (AMP. It is well known that in fatty liver, activity of the AMP-activated kinase (AMPK is reduced and that its stimulation can prevent hepatic steatosis by both enhancing fat oxidation and reducing lipogenesis. Here we show that another AMP dependent enzyme, AMPD2, has opposing effects on fatty acid oxidation when compared to AMPK. In human hepatocytres, AMPD2 activation -either by overexpression or by lowering intracellular phosphate levels with fructose- is associated with a significant reduction in AMPK activity. Likewise, silencing of AMPK spontaneously increases AMPD activity, demonstrating that these enzymes counter-regulate each other. Furthermore, we show that a downstream product of AMP metabolism through AMPD2, uric acid, can inhibit AMPK activity in human hepatocytes. Finally, we show that fructose-induced fat accumulation in hepatocytes is due to a dominant stimulation of AMPD2 despite stimulating AMPK. In this regard, AMPD2-deficient hepatocytes demonstrate a further activation of AMPK after fructose exposure in association with increased fatty acid oxidation, and conversely silencing AMPK enhances AMPD-dependent fat accumulation. In vivo, we show that sucrose fed rats also develop fatty liver that is blocked by metformin in association with both a reduction in AMPD activity and an increase in AMPK activity. In summary, AMPD and AMPK are both important in hepatic fat accumulation and counter-regulate each other. We present the novel finding that uric acid inhibits AMPK kinase activity in fructose-fed hepatocytes thus providing new insights into the pathogenesis of fatty liver.

  10. An approach to counteracting long-term microgravity-induced muscle atrophy

    Science.gov (United States)

    Tesch, P. A.; Buchanan, P.; Dudley, G. A.

    1990-01-01

    To find means of alleviating muscle atrophy induced by long-term microgravity, the effects of a 19-week-long heavy-resistance training regime (using either concentric muscle actions only or concentric and eccentric muscle actions) on the strengths of the exercised knee extensor muscle group were investigated in two groups of male human subjects performing two types of training exercises: supine leg press or/and seated knee extension. Results show that a training program in which both the concentric and the eccentric muscle action was performed led to substantially greater increases in maximal muscle strength than when only concentric exercises were performed.

  11. An approach to counteracting long-term microgravity-induced muscle atrophy

    Science.gov (United States)

    Tesch, P. A.; Buchanan, P.; Dudley, G. A.

    1990-01-01

    To find means of alleviating muscle atrophy induced by long-term microgravity, the effects of a 19-week-long heavy-resistance training regime (using either concentric muscle actions only or concentric and eccentric muscle actions) on the strengths of the exercised knee extensor muscle group were investigated in two groups of male human subjects performing two types of training exercises: supine leg press or/and seated knee extension. Results show that a training program in which both the concentric and the eccentric muscle action was performed led to substantially greater increases in maximal muscle strength than when only concentric exercises were performed.

  12. Simvastatin enhances protection against Listeria monocytogenes infection in mice by counteracting Listeria-induced phagosomal escape.

    Directory of Open Access Journals (Sweden)

    Suraj P Parihar

    Full Text Available Statins are well-known cholesterol lowering drugs targeting HMG-CoA-reductase, reducing the risk of coronary disorders and hypercholesterolemia. Statins are also involved in immunomodulation, which might influence the outcome of bacterial infection. Hence, a possible effect of statin treatment on Listeriosis was explored in mice. Statin treatment prior to subsequent L. monocytogenes infection strikingly reduced bacterial burden in liver and spleen (up to 100-fold and reduced histopathological lesions. Statin-treatment in infected macrophages resulted in increased IL-12p40 and TNF-α and up to 4-fold reduced bacterial burden within 6 hours post infection, demonstrating a direct effect of statins on limiting bacterial growth in macrophages. Bacterial uptake was normal investigated in microbeads and GFP-expressing Listeria experiments by confocal microscopy. However, intracellular membrane-bound cholesterol level was decreased, as analyzed by cholesterol-dependent filipin staining and cellular lipid extraction. Mevalonate supplementation restored statin-inhibited cholesterol biosynthesis and reverted bacterial growth in Listeria monocytogenes but not in listeriolysin O (LLO-deficient Listeria. Together, these results suggest that statin pretreatment increases protection against L. monocytogenes infection by reducing membrane cholesterol in macrophages and thereby preventing effectivity of the cholesterol-dependent LLO-mediated phagosomal escape of bacteria.

  13. 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.

  14. 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.

  15. Behavioral benefits of maternal swimming are counteracted by neonatal hypoxia-ischemia in the offspring.

    Science.gov (United States)

    Marcelino, Thiago Beltram; de Lemos Rodrigues, Patricia Idalina; Klein, Caroline Peres; Santos, Bernardo Gindri Dos; Miguel, Patrícia Maidana; Netto, Carlos Alexandre; Silva, Lenir Orlandi Pereira; Matté, Cristiane

    2016-10-01

    Hypoxia-ischemia (HI) represents one of the most common causes of neonatal encephalopathy. The central nervous system injury comprises several mechanisms, including inflammatory, excitotoxicity, and redox homeostasis unbalance leading to cell death and cognitive impairment. Exercise during pregnancy is a potential therapeutic tool due to benefits offered to mother and fetus. Swimming during pregnancy elicits a strong metabolic programming in the offspring's brain, evidenced by increased antioxidant enzymes, mitochondrial biogenesis, and neurogenesis. This article aims to evaluate whether the benefits of maternal exercise are able to prevent behavioral brain injury caused by neonatal HI. Female adult Wistar rats swam before and during pregnancy (30min/day, 5 days/week, 4 weeks). At 7(th) day after birth, the offspring was submitted to HI protocol and, in adulthood (60(th) day), it performed the behavioral tests. It was observed an increase in motor activity in the open field test in HI-rats, which was not prevented by maternal exercise. The rats subjected to maternal swimming presented an improved long-term memory in the object recognition task, which was totally reversed by neonatal HI encephalopathy. BDNF brain levels were not altered; suggesting that HI or maternal exercise effects were BDNF-independent. In summary, our data suggest a beneficial long-term effect of maternal swimming, despite not being robust enough to protect from HI injury. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Combined approach to counteract experimental cancer cachexia: eicosapentaenoic acid and training exercise.

    Science.gov (United States)

    Penna, Fabio; Busquets, Silvia; Pin, Fabrizio; Toledo, Miriam; Baccino, Francesco M; López-Soriano, Francisco J; Costelli, Paola; Argilés, Josep M

    2011-06-01

    BACKGROUND: Cancer cachexia is a syndrome characterized by loss of skeletal muscle protein, depletion of lipid stores, anorexia, weakness, and perturbations of the hormonal homeostasis. Despite several therapeutic approaches described in the past, effective interventions countering cancer cachexia are still lacking. METHODS: The present work was aimed to verify the ability of eicosapentaenoic acid (EPA) to prevent the muscle depletion in Lewis lung carcinoma-bearing mice and to test the ability of endurance exercise training to increase the EPA effect. RESULTS: EPA alone did not prevent the muscle loss induced by tumor growth while the combination with exercise induced a partial rescue of muscle strength and mass. Moreover, the association of EPA and exercise reduced the dramatic PAX-7 accumulation and stimulated the increase of PCG-1 protein. CONCLUSIONS: Overall, the present data suggest that exercise is an effective tool that should be added for combined therapeutic approaches against cancer cachexia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13539-011-0028-4) contains supplementary material, which is available to authorized users.

  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. Modulation of the Unfolded Protein Response by Tauroursodeoxycholic Acid Counteracts Apoptotic Cell Death and Fibrosis in a Mouse Model for Secondary Biliary Liver Fibrosis.

    Science.gov (United States)

    Paridaens, Annelies; Raevens, Sarah; Devisscher, Lindsey; Bogaerts, Eliene; Verhelst, Xavier; Hoorens, Anne; Van Vlierberghe, Hans; van Grunsven, Leo A; Geerts, Anja; Colle, Isabelle

    2017-01-20

    The role of endoplasmic reticulum stress and the unfolded protein response (UPR) in cholestatic liver disease and fibrosis is not fully unraveled. Tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid, has been shown to reduce endoplasmic reticulum (ER) stress and counteract apoptosis in different pathologies. We aimed to investigate the therapeutic potential of TUDCA in experimental secondary biliary liver fibrosis in mice, induced by common bile duct ligation. The kinetics of the hepatic UPR and apoptosis during the development of biliary fibrosis was studied by measuring markers at six different timepoints post-surgery by qPCR and Western blot. Next, we investigated the therapeutic potential of TUDCA, 10 mg/kg/day in drinking water, on liver damage (AST/ALT levels) and fibrosis (Sirius red-staining), in both a preventive and therapeutic setting. Common bile duct ligation resulted in the increased protein expression of CCAAT/enhancer-binding protein homologous protein (CHOP) at all timepoints, along with upregulation of pro-apoptotic caspase 3 and 12, tumor necrosis factor receptor superfamily, member 1A (TNFRsf1a) and Fas-Associated protein with Death Domain (FADD) expression. Treatment with TUDCA led to a significant reduction of liver fibrosis, accompanied by a slight reduction of liver damage, decreased hepatic protein expression of CHOP and reduced gene and protein expression of pro-apoptotic markers. These data indicate that TUDCA exerts a beneficial effect on liver fibrosis in a model of cholestatic liver disease, and suggest that this effect might, at least in part, be attributed to decreased hepatic UPR signaling and apoptotic cell death.

  19. Increase in Rubisco activity and gene expression due to elevated temperature partially counteracts ultraviolet radiation-induced photoinhibition in the marine diatom Thalassiosira weissflogii

    NARCIS (Netherlands)

    Walter Helbling, E.; Buma, Anita G. J.; Boelen, Peter; van der Strate, Han J.; Fiorda Giordanino, M. Valeria; Villafane, Virginia E.

    2011-01-01

    We performed outdoor experiments to evaluate the effect of temperature on photoinhibition properties in the cosmopolitan diatom Thalassiosira weissflogii. Cultures were exposed to solar radiation with or without ultraviolet radiation (UVR, 280-400 nm), UV-A (320-400 nm), and UV-B (280-320 nm) at bot

  20. 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 i

  1. Biotic interference in parasite transmission: Can the feeding of anemones counteract an increased risk of parasitism in amphipods at higher temperature?

    NARCIS (Netherlands)

    Studer, A.; Kremer, L.; Nelles, J.; Poulin, R.; Thieltges, D.W.

    2013-01-01

    The transmission of parasites is embedded in the complexity of natural systems and is influenced not only by prevailing abiotic conditions, but also by the composition of the ambient community. In particular, temperature affects the number of transmission stages (e.g. cercariae of trematodes)

  2. 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.

  3. 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.

  4. Antioxidant treatments counteract the non-culturability of bacterial endophytes isolated from legume nodules.

    Science.gov (United States)

    Muresu, Rosella; Tondello, Alessandra; Polone, Elisa; Sulas, Leonardo; Baldan, Barbara; Squartini, Andrea

    2013-06-01

    In many wild legumes, attempts to cultivate nodule bacteria fail. We hypothesized that the limited culturability could be related to injury from oxidative stress caused by disruption of plant tissues during isolation. To test that, we isolated bacteria from nodules of Hedysarum spinosissimum and Tetragonolobus purpureus using buffers supplemented with scavenging systems to prevent damage from reactive oxygen species (ROS). Treatments included the following: antioxidants (glutathione, ascorbate, EDTA) or enzymes (catalase, peroxidase, superoxide dismutase), tested either as modified squashing buffers or added in plates. Some combinations yielded dramatic increases of culturability. Different endophytes were found, including additional Rhizobiaceae that were not the primary symbiont and were unable to nodulate. Their H2O2 tolerance in broth culture showed differences consistent with the unequal culturability observed. In wild legumes species, ROS generation during extraction appears to be a major factor limiting microbiota isolation, and protocols presented here significantly improve the recovery of culturable bacterial endophytes from plants.

  5. High dietary calcium intake does not counteract disuse-induced bone loss

    Science.gov (United States)

    Baecker, N.; Boese, A.; Smith, S. M.; Heer, M.

    Reduction of mechanical stress on bone inhibits osteoblast-mediated bone formation, increases osteoclast-mediated bone resorption, and leads to what has been called disuse osteoporosis. Prolonged therapeutic bed rest, immobilization and space flight are common causes of disuse osteoporosis. There are sufficient data supporting the use of calcium in combination with vitamin D in the prevention and treatment of postmenopausal osteoporosis. In our study we examined the potential of high dietary calcium intake as a nutrition therapy for disuse-induced bone loss during head-down bed rest in healthy young men. In 2 identical metabolic ward, head-down bed rest (HDBR) experiments (crossover design), we studied the effect of high dietary calcium intake (2000 mg/d) in comparison to the recommended calcium intake of 1000 mg/d on markers of bone turnover. Experiment A (EA) was a 6-day randomized, controlled HDBR study. Experiment B (EB) was a 14-day randomized, controlled HDBR study. In both experiments, the test subjects stayed under well-controlled environmental conditions in our metabolic ward. Subjects' diets in the relevant study phases (HDBR versus Ambulatory Control) of EA and EB were identical except for the calcium intake. The subjects obtained 2000 mg/d Calcium in EA and 2000 mg/d in EB. Blood was drawn at baseline, before entering the relevant intervention period, on day 5 in study EA, and on days 6, 11 and 14 in study EB. Serum calcium, bone formation markers - Procollagen-I-C-Propeptide (PICP) and bone alkaline phosphatase (bAP) were analyzed in serum. 24h-urine was collected throughout the studies for determination of the excretion of calcium (UCaV) and a bone resorption marker, C-terminal telopeptide of collagen type I (UCTX). In both studies, serum calcium levels were unchanged. PICP tended to decrease in EA (p=0.08). In EB PICP decreased significantly over time (p=0.003) in both the control and HDBR periods, and tended to further decrease in the HDBR period (p

  6. Intracerebroventricular urocortin 3 counteracts central acyl ghrelin-induced hyperphagic and gastroprokinetic effects via CRF receptor 2 in rats

    Directory of Open Access Journals (Sweden)

    Yeh C

    2016-10-01

    Full Text Available Chun Yeh,1 Ching-Heng Ting,2 Ming-Luen Doong,3 Chin-Wen Chi,4,5 Shou-Dong Lee,1 Chih-Yen Chen6–8 1Division of Gastroenterology, Department of Internal Medicine, Cheng-Hsin General Hospital, 2Department of Pathology, Mackay Memorial Hospital, 3Institute of Physiology, 4Institute of Pharmacology, National Yang-Ming University School of Medicine, 5Department of Medical Research, Taipei Veterans General Hospital, 6Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, 7Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, 8Taiwan Association for the Study of Small Intestinal Diseases, Guishan, Taiwan Purpose: Urocortin 3 is a key neuromodulator in the regulation of stress, anxiety, food intake, gut motility, and energy homeostasis, while ghrelin elicits feeding behavior and enhances gastric emptying, adiposity, and positive energy balance. However, the interplays between urocortin 3 and ghrelin on food intake and gastric emptying remain uninvestigated.Methods: We examined the differential effects of central O-n-octanoylated ghrelin, des-Gln14-ghrelin, and urocortin 3 on food intake, as well as on charcoal nonnutrient semiliquid gastric emptying in conscious rats that were chronically implanted with intracerebroventricular (ICV catheters. The functional importance of corticotropin-releasing factor (CRF receptor 2 in urocortin 3-induced responses was examined by ICV injection of the selective CRF receptor 2 antagonist, astressin2-B.Results: ICV infusion of urocortin 3 opposed central acyl ghrelin-elicited hyperphagia via CRF receptor 2 in satiated rats. ICV injection of O-n-octanoylated ghrelin and des-Gln14-ghrelin were equally potent in accelerating gastric emptying in fasted rats, whereas ICV administration of urocortin 3 delayed gastric emptying. In addition, ICV infusion of urocortin 3 counteracted central acyl ghrelin-induced gastroprokinetic effects via CRF receptor 2

  7. β2-adrenergic stimulation enhances Ca2+ release and contractile properties of skeletal muscles, and counteracts exercise-induced reductions in Na+/K+-ATPase Vmax in trained men

    DEFF Research Database (Denmark)

    Hostrup, Morten; Kalsen, A; Ortenblad, N

    2014-01-01

    The aim of the present study was to examine the effect of beta2-adrenergic stimulation on skeletal muscle contractile properties, sarcoplasmic reticulum (SR) rates of Ca(2+) release and uptake, and Na(+)/K(+)-ATPase-activity before and after fatiguing exercise in trained men. The study consisted......-fatigue, but terbutaline counteracted exercise-induced reductions in Vmax at time of fatigue. In conclusion, increased contractile force induced by beta2-adrenergic stimulation is associated with enhanced rate of Ca(2+) release in humans. While beta2-adrenergic stimulation elicits positive inotropic and lusitropic effects...... of two experiments (EXP1, n = 10 M, EXP2, n = 20 M), where beta2-adrenoceptor agonist (terbutaline) or placebo was randomly administered in double-blinded crossover designs. In EXP1, maximal voluntary isometric contraction of m.quadriceps (MVC) was measured, followed by exercise to fatigue at 120% of Vo2...

  8. 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.

  9. Fibrin/platelet plug counteracts cutaneous wound contraction: the hypothesis of "skipping stone".

    Science.gov (United States)

    Farahani, Ramin Mostofi Zadeh

    2007-01-01

    Cutaneous wound contraction and epithelialization act collaboratively to minimize the exposed wound surface. However excessive wound contraction is undesirable due to the resultant disfigurement and scarring. Fibrin clot has greater stiffness than surrounding tissue and mechanical strain further enhances its stiffness. On the contrary, skin exhibits diminished stiffness when affected by high strain rates. Therefore during early stages of wound healing, the contractile wound border is confronted by fibrin clot forming a high strain region in the interface of contractile tissue and fibrin clot--which is evidenced by computer simulation. Due to the stress relaxation property of skin, the contractile strain is partly neutralized. Meanwhile, gradually the stiffness of fibrin clot decreases which is followed by another cycle of wound contraction. This cyclic pattern of contraction resembles the movement of a stone over water or "skipping stone". The stone bounces repeatedly when thrown across the surface of water with reduction of jumping altitude with each bounce till the stone stops completely. This hypothesis is further supported by the observed initial delay in wound contraction and the chronological correlation of enhanced wound contraction with loss of superficial eschar and substitution of fibrin clot with granulation tissue. Also there is evidence that fibrin inhibits fibroblast-mediated contraction of collagen. Furthermore, modest increase in wound contraction rate in fibrinogen deficient mice and fibrin-mediated diminished wound contraction are agreement with the proposed hypothesis.

  10. The acute phase of experimental cardiogenic shock is counteracted by microcirculatory and mitochondrial adaptations.

    Directory of Open Access Journals (Sweden)

    Thor Allan Stenberg

    Full Text Available The mechanisms contributing to multiorgan dysfunction during cardiogenic shock are poorly understood. Our goal was to characterize the microcirculatory and mitochondrial responses following ≥ 10 hours of severe left ventricular failure and cardiogenic shock. We employed a closed-chest porcine model of cardiogenic shock induced by left coronary microembolization (n = 12 and a time-matched control group (n = 6. Hemodynamics and metabolism were measured hourly by intravascular pressure catheters, thermodilution, arterial and organ specific blood gases. Echocardiography and assessment of the sublingual microcirculation by sidestream darkfield imaging were performed at baseline, 2 ± 1 and 13 ± 3 (mean ± SD hours after coronary microembolization. Upon hemodynamic decompensation, cardiac, renal and hepatic mitochondria were isolated and evaluated by high-resolution respirometry. Low cardiac output, hypotension, oliguria and severe reductions in mixed-venous and hepatic O2 saturations were evident in cardiogenic shock. The sublingual total and perfused vessel densities were fully preserved throughout the experiments. Cardiac mitochondrial respiration was unaltered, whereas state 2, 3 and 4 respiration of renal and hepatic mitochondria were increased in cardiogenic shock. Mitochondrial viability (RCR; state 3/state 4 and efficiency (ADP/O ratio were unaffected. Our study demonstrates that the microcirculation is preserved in a porcine model of untreated cardiogenic shock despite vital organ hypoperfusion. Renal and hepatic mitochondrial respiration is upregulated, possibly through demand-related adaptations, and the endogenous shock response is thus compensatory and protective, even after several hours of global hypoperfusion.

  11. Accentuate the positive: Counteracting psychogenic responses to media health messages in the age of the Internet.

    Science.gov (United States)

    Crichton, Fiona; Petrie, Keith J

    2015-09-01

    The Internet has expanded the scope for creating health scares and increased the risk of nocebo responding in individuals exposed to misinformation about threats to personal health posed by aspects of modern life, such as exposure to new technologies. It was the aim of this experiment to investigate whether the delivery of positive expectations might reduce or reverse symptoms triggered by negative expectations formed from such misinformation. In the context of a study investigating symptoms during exposure to windfarm sound, 64 volunteers assessed their symptomatic experiences during two discrete sessions, throughout which they listened to wind turbine sound containing audible and sub-audible (infrasound) components. Participants were randomly assigned to watch either positive or negative information about the health effects of infrasound prior to their first infrasound exposure session. They were then shown the alternate information and exposed to infrasound during their second session. Participants receiving negative expectations were less symptomatic during exposure if they had previously received positive expectations about infrasound. Further, participants given positive expectations after the earlier delivery of negative expectations exhibited a placebo response, reversing the nocebo response exhibited in their first exposure session. Results suggest accessing positively framed health information may reverse or dilute the effect of negative expectations formed from exposure to media warnings about health risks posed by new technologies, such as wind turbines. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. The acute phase of experimental cardiogenic shock is counteracted by microcirculatory and mitochondrial adaptations.

    Science.gov (United States)

    Stenberg, Thor Allan; Kildal, Anders Benjamin; Sanden, Espen; How, Ole-Jakob; Hagve, Martin; Ytrehus, Kirsti; Larsen, Terje S; Myrmel, Truls

    2014-01-01

    The mechanisms contributing to multiorgan dysfunction during cardiogenic shock are poorly understood. Our goal was to characterize the microcirculatory and mitochondrial responses following ≥ 10 hours of severe left ventricular failure and cardiogenic shock. We employed a closed-chest porcine model of cardiogenic shock induced by left coronary microembolization (n = 12) and a time-matched control group (n = 6). Hemodynamics and metabolism were measured hourly by intravascular pressure catheters, thermodilution, arterial and organ specific blood gases. Echocardiography and assessment of the sublingual microcirculation by sidestream darkfield imaging were performed at baseline, 2 ± 1 and 13 ± 3 (mean ± SD) hours after coronary microembolization. Upon hemodynamic decompensation, cardiac, renal and hepatic mitochondria were isolated and evaluated by high-resolution respirometry. Low cardiac output, hypotension, oliguria and severe reductions in mixed-venous and hepatic O2 saturations were evident in cardiogenic shock. The sublingual total and perfused vessel densities were fully preserved throughout the experiments. Cardiac mitochondrial respiration was unaltered, whereas state 2, 3 and 4 respiration of renal and hepatic mitochondria were increased in cardiogenic shock. Mitochondrial viability (RCR; state 3/state 4) and efficiency (ADP/O ratio) were unaffected. Our study demonstrates that the microcirculation is preserved in a porcine model of untreated cardiogenic shock despite vital organ hypoperfusion. Renal and hepatic mitochondrial respiration is upregulated, possibly through demand-related adaptations, and the endogenous shock response is thus compensatory and protective, even after several hours of global hypoperfusion.

  13. Schwann cell autophagy counteracts the onset and chronification of neuropathic pain.

    Science.gov (United States)

    Marinelli, Sara; Nazio, Francesca; Tinari, Antonella; Ciarlo, Laura; D'Amelio, Marcello; Pieroni, Luisa; Vacca, Valentina; Urbani, Andrea; Cecconi, Francesco; Malorni, Walter; Pavone, Flaminia

    2014-01-01

    Axonal degeneration in peripheral nerves after injury is accompanied by myelin degradation initiated by Schwann cells (SCs). These cells activate autophagy, a ubiquitous cytoprotective process essential for degradation and recycling of cellular constituents. Concomitantly to nerve insult and axonal degeneration, neuropathic pain (NeP) arises. The role of SC autophagy in the mechanisms underlying NeP is still unknown. In this study, we examined the role of the autophagy during the early phase of Wallerian degeneration in NeP induction and chronification by using a murine model of peripheral nerve lesion (chronic constriction injury). We demonstrate that the autophagy inducer rapamycin, administered in the first week after nerve damage, induces long-lasting analgesic and antiinflammatory effects, facilitates nerve regeneration, and prevents pain chronification. Conversely, when autophagy is altered, by means of autophagic inhibitor 3-methyladenine administration or as occurs in activating molecule in Beclin-1-regulated autophagy transgenic mice (Ambra1(+/gt)), NeP is dramatically enhanced and prolonged. Immunohistochemical and ultrastructural evaluations show that rapamycin is able to increase autophagic flux in SCs, to accelerate myelin compaction, and to reduce inflammatory and immune reaction. Proteomic analysis combined with bioinformatic analysis suggests that a redox-sensitive mechanism could be responsible for SC autophagy activation. These data suggest that a deficiency of autophagic activity in SCs can be an early event in the origin of NeP chronification and that autophagy modulation may represent a powerful pharmacological approach to prevent the onset and chronification of NeP in the clinical setting.

  14. Role of silicon counteracting cadmium toxicity in Alfalfa (Medicago sativa L.

    Directory of Open Access Journals (Sweden)

    Ahmad H. Kabir

    2016-07-01

    Full Text Available Cadmium (Cd is one of the most phytotoxic elements causing an agricultural problem and human health hazards. This work investigates whether and how silicon (Si ameliorates Cd toxicity in Alfalfa. The addition of Si in Cd-stressed plants caused significant improvement in morpho-physiological features as well as total protein and membrane stability, indicating that Si does have critical roles in Cd detoxification in Alfalfa. Furthermore, Si supplementation in Cd-stressed plants showed a significant decrease in Cd and Fe concentrations in both roots and shoots compared with Cd-stressed plants, revealing that Si-mediated tolerance to Cd stress is associated with Cd inhibition in Alfalfa. Results also showed no significant changes in the expression of two metal chelators [MsPCS1 (phytochelatin synthase and MsMT2 (metallothionein] and PC (phytochelatin accumulation, indicating that there may be no metal sequestration or change in metal sequestration following Si application under Cd stress in Alfalfa. We further performed a targeted study on the effect of Si on Fe uptake mechanisms. We observed the consistent reduction in Fe reductase activity, expression of Fe-related genes [MsIRT1 (Fe transporter, MsNramp1 (metal transporter and OsFRO1 (ferric chelate reductase] and Fe chelators (citrate and malate by Si application to Cd stress in roots of Alfalfa. These results support that limiting Fe uptake through the down-regulation of Fe acquisition mechanisms confers Si-mediated alleviation of Cd toxicity in Alfalfa. Finally, an increase of catalase (CAT, ascorbate peroxidase (APX and superoxide dismutase (SOD activities along with elevated methionine and proline subjected to Si application might play roles, at least in part, to reduce H2O2 and to provide antioxidant defense against Cd stress in Alfalfa. The study shows evidence of the effect of Si on alleviating Cd toxicity in Alfalfa and can be further extended for phytoremediation of Cd toxicity in plants.

  15. 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

  16. Role of Silicon Counteracting Cadmium Toxicity in Alfalfa (Medicago sativa L.)

    Science.gov (United States)

    Kabir, Ahmad H.; Hossain, Mohammad M.; Khatun, Most A.; Mandal, Abul; Haider, Syed A.

    2016-01-01

    Cadmium (Cd) is one of the most phytotoxic elements causing an agricultural problem and human health hazards. This work investigates whether and how silicon (Si) ameliorates Cd toxicity in Alfalfa. The addition of Si in Cd-stressed plants caused significant improvement in morpho-physiological features as well as total protein and membrane stability, indicating that Si does have critical roles in Cd detoxification in Alfalfa. Furthermore, Si supplementation in Cd-stressed plants showed a significant decrease in Cd and Fe concentrations in both roots and shoots compared with Cd-stressed plants, revealing that Si-mediated tolerance to Cd stress is associated with Cd inhibition in Alfalfa. Results also showed no significant changes in the expression of two metal chelators [MsPCS1 (phytochelatin synthase) and MsMT2 (metallothionein)] and PC (phytochelatin) accumulation, indicating that there may be no metal sequestration or change in metal sequestration following Si application under Cd stress in Alfalfa. We further performed a targeted study on the effect of Si on Fe uptake mechanisms. We observed the consistent reduction in Fe reductase activity, expression of Fe-related genes [MsIRT1 (Fe transporter), MsNramp1 (metal transporter) and OsFRO1 (ferric chelate reductase] and Fe chelators (citrate and malate) by Si application to Cd stress in roots of Alfalfa. These results support that limiting Fe uptake through the down-regulation of Fe acquisition mechanisms confers Si-mediated alleviation of Cd toxicity in Alfalfa. Finally, an increase of catalase, ascorbate peroxidase, and superoxide dismutase activities along with elevated methionine and proline subjected to Si application might play roles, at least in part, to reduce H2O2 and to provide antioxidant defense against Cd stress in Alfalfa. The study shows evidence of the effect of Si on alleviating Cd toxicity in Alfalfa and can be further extended for phytoremediation of Cd toxicity in plants. PMID:27512401

  17. Role of Silicon Counteracting Cadmium Toxicity in Alfalfa (Medicago sativa L.).

    Science.gov (United States)

    Kabir, Ahmad H; Hossain, Mohammad M; Khatun, Most A; Mandal, Abul; Haider, Syed A

    2016-01-01

    Cadmium (Cd) is one of the most phytotoxic elements causing an agricultural problem and human health hazards. This work investigates whether and how silicon (Si) ameliorates Cd toxicity in Alfalfa. The addition of Si in Cd-stressed plants caused significant improvement in morpho-physiological features as well as total protein and membrane stability, indicating that Si does have critical roles in Cd detoxification in Alfalfa. Furthermore, Si supplementation in Cd-stressed plants showed a significant decrease in Cd and Fe concentrations in both roots and shoots compared with Cd-stressed plants, revealing that Si-mediated tolerance to Cd stress is associated with Cd inhibition in Alfalfa. Results also showed no significant changes in the expression of two metal chelators [MsPCS1 (phytochelatin synthase) and MsMT2 (metallothionein)] and PC (phytochelatin) accumulation, indicating that there may be no metal sequestration or change in metal sequestration following Si application under Cd stress in Alfalfa. We further performed a targeted study on the effect of Si on Fe uptake mechanisms. We observed the consistent reduction in Fe reductase activity, expression of Fe-related genes [MsIRT1 (Fe transporter), MsNramp1 (metal transporter) and OsFRO1 (ferric chelate reductase] and Fe chelators (citrate and malate) by Si application to Cd stress in roots of Alfalfa. These results support that limiting Fe uptake through the down-regulation of Fe acquisition mechanisms confers Si-mediated alleviation of Cd toxicity in Alfalfa. Finally, an increase of catalase, ascorbate peroxidase, and superoxide dismutase activities along with elevated methionine and proline subjected to Si application might play roles, at least in part, to reduce H2O2 and to provide antioxidant defense against Cd stress in Alfalfa. The study shows evidence of the effect of Si on alleviating Cd toxicity in Alfalfa and can be further extended for phytoremediation of Cd toxicity in plants.

  18. Sorbitol counteracts temperature- and chemical-induced denaturation of a recombinant α-amylase from alkaliphilic Bacillus sp. TS-23.

    Science.gov (United States)

    Chi, Meng-Chun; Wu, Tai-Jung; Chen, Hsing-Ling; Lo, Huei-Fen; Lin, Long-Liu

    2012-12-01

    Enzymes are highly complex systems with a substantial degree of structural variability in their folded state. In the presence of cosolvents, fluctuations among vast numbers of folded and unfolded conformations occur via many different pathways; alternatively, certain conformations can be stabilized or destabilized. To understand the contribution of osmolytes to the stabilization of structural changes and enzymatic activity of a truncated Bacillus sp. TS-23 α-amylase (BACΔNC), we monitored amylolytic activity, circular dichroism, and fluorescence as a function of osmolytes. In the presence of trimethylamine N-oxide (TMAO) and sorbitol, BACΔNC activity was retained significantly at elevated temperatures. As compared to the control, the secondary structures of this enzyme were essentially conserved upon the addition of these two kinds of osmolytes. Fluorescence results revealed that the temperature-induced conformational change of BACΔNC was prevented by TMAO and sorbitol. However, glycerol did not provide profound protection against thermal denaturation of the enzyme. Sorbitol was further found to counteract guanidine hydrochloride- and SDS-induced denaturation of BACΔNC. Thus, some well-known naturally occurring osmolytes make a dominant contribution to the stabilization of BACΔNC.

  19. 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.

  20. The counteracting effect of potassium cyanide in sodium azide-inhibited germination of Paulownia tomentosa  Steud. seeds

    Directory of Open Access Journals (Sweden)

    Živković Suzana

    2005-01-01

    Full Text Available The effect of some respiratory inhibitors on light-induced Paulownia tomentosa Steud. seed germination was studied. Millimolar solution of sodium azide was sufficient to completely prevent germination induced by a 5-min red light pulse. The inhibitory effect of azide was absent if seeds were rinsed before phytochrome activation by light. Sodium azide was effective only if present in the period of Pfr activity. The escape time from azide inhibition compared to the escape from far-red light action, was delayed for about 24 hours. When azide was applied after phytochrome activation, its effect depended on how long it was present in the incubation medium. The removal of azide allowed full restoration of germination by another red light pulse and the far-red escape time did not differ from the escape of untreated, i.e. water-imbibed seeds. Potassium cyanide alone did not produce any effect in light-stimulated germination of these seeds. However, it counteracted the inhibitory effect of azide in light-stimulated germination, if applied simultaneously at a concentration three times higher.

  1. 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.

  2. ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction.

    Science.gov (United States)

    Miyakawa, Kei; Matsunaga, Satoko; Kanou, Kazuhiko; Matsuzawa, Atsushi; Morishita, Ryo; Kudoh, Ayumi; Shindo, Keisuke; Yokoyama, Masaru; Sato, Hironori; Kimura, Hirokazu; Tamura, Tomohiko; Yamamoto, Naoki; Ichijo, Hidenori; Takaori-Kondo, Akifumi; Ryo, Akihide

    2015-04-22

    APOBEC3G (A3G) is an innate antiviral restriction factor that strongly inhibits the replication of human immunodeficiency virus type 1 (HIV-1). An HIV-1 accessory protein, Vif, hijacks the host ubiquitin-proteasome system to execute A3G degradation. Identification of the host pathways that obstruct the action of Vif could provide a new strategy for blocking viral replication. We demonstrate here that the host protein ASK1 (apoptosis signal-regulating kinase 1) interferes with the counteraction by Vif and revitalizes A3G-mediated viral restriction. ASK1 binds the BC-box of Vif, thereby disrupting the assembly of the Vif-ubiquitin ligase complex. Consequently, ASK1 stabilizes A3G and promotes its incorporation into viral particles, ultimately reducing viral infectivity. Furthermore, treatment with the antiretroviral drug AZT (zidovudine) induces ASK1 expression and restores the antiviral activity of A3G in HIV-1-infected cells. This study thus demonstrates a distinct function of ASK1 in restoring the host antiviral system that can be enhanced by AZT treatment.

  3. Mammalian ribosomal and chaperone protein RPS3A counteracts α-synuclein aggregation and toxicity in a yeast model system.

    Science.gov (United States)

    De Graeve, Stijn; Marinelli, Sarah; Stolz, Frank; Hendrix, Jelle; Vandamme, Jurgen; Engelborghs, Yves; Van Dijck, Patrick; Thevelein, Johan M

    2013-11-01

    Accumulation of aggregated forms of αSyn (α-synuclein) into Lewy bodies is a known hallmark associated with neuronal cell death in Parkinson's disease. When expressed in the yeast Saccharomyces cerevisiae, αSyn interacts with the plasma membrane, forms inclusions and causes a concentration-dependent growth defect. We have used a yeast mutant, cog6Δ, which is particularly sensitive to moderate αSyn expression, for screening a mouse brain-specific cDNA library in order to identify mammalian proteins that counteract αSyn toxicity. The mouse ribosomal and chaperone protein RPS3A was identified as a suppressor of αSyn [WT (wild-type) and A53T] toxicity in yeast. We demonstrated that the 50 N-terminal amino acids are essential for this function. The yeast homologues of RPS3A were not effective in suppressing the αSyn-induced growth defect, illustrating the potential of our screening system to identify modifiers that would be missed using yeast gene overexpression as the first screening step. Co-expression of mouse RPS3A delayed the formation of αSyn-GFP inclusions in the yeast cells. The results of the present study suggest that the recently identified extraribosomal chaperonin function of RPS3A also acts on the neurodegeneration-related protein αSyn and reveal a new avenue for identifying promising candidate mammalian proteins involved in αSyn functioning.

  4. Structurally Distinct Bacterial TBC-like GAPs Link Arf GTPase to Rab1 Inactivation to Counteract Host Defenses

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Na; Zhu, Yongqun; Lu, Qiuhe; Hu, Liyan; Zheng, Yuqing; Shao, Feng (NIBS-China); (Zhejiang)

    2012-10-10

    Rab GTPases are frequent targets of vacuole-living bacterial pathogens for appropriate trafficking of the vacuole. Here we discover that bacterial effectors including VirA from nonvacuole Shigella flexneri and EspG from extracellular Enteropathogenic Escherichia coli (EPEC) harbor TBC-like dual-finger motifs and exhibits potent RabGAP activities. Specific inactivation of Rab1 by VirA/EspG disrupts ER-to-Golgi trafficking. S. flexneri intracellular persistence requires VirA TBC-like GAP activity that mediates bacterial escape from autophagy-mediated host defense. Rab1 inactivation by EspG severely blocks host secretory pathway, resulting in inhibited interleukin-8 secretion from infected cells. Crystal structures of VirA/EspG-Rab1-GDP-aluminum fluoride complexes highlight TBC-like catalytic role for the arginine and glutamine finger residues and reveal a 3D architecture distinct from that of the TBC domain. Structure of Arf6-EspG-Rab1 ternary complex illustrates a pathogenic signaling complex that rewires host Arf signaling to Rab1 inactivation. Structural distinctions of VirA/EspG further predict a possible extensive presence of TBC-like RabGAP effectors in counteracting various host defenses.

  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. Can a reduction of solar irradiance counteract CO2-induced climate change? – Results from four Earth system models

    Directory of Open Access Journals (Sweden)

    M. Lawrence

    2012-01-01

    Full Text Available In this study we compare the response of four state-of-the-art Earth system models to climate engineering under scenario G1 of the GeoMIP and IMPLICC model intercomparison projects. In G1, the radiative forcing from an instantaneous quadrupling of the CO2 concentration, starting from the preindustrial level, is balanced by a reduction of the solar constant. Model responses to the two counteracting forcings in G1 are compared to the preindustrial climate in terms of global means and regional patterns and their robustness. While the global mean surface air temperature in G1 remains almost unchanged, the meridional temperature gradient is reduced in all models compared to the control simulation. Another robust response is the global reduction of precipitation with strong effects in particular over North and South America and northern Eurasia. It is shown that this reduction is only partly compensated by a reduction in evaporation so that large continental regions are drier in the engineered climate. In comparison to the climate response to a quadrupling of CO2 alone the temperature responses are small in experiment G1. Precipitation responses are, however, of comparable magnitude but in many regions of opposite sign.

  7. Implications of sit-stand and active workstations to counteract the adverse effects of sedentary work: A comprehensive review.

    Science.gov (United States)

    Karol, Sohit; Robertson, Michelle M

    2015-01-01

    Sedentary work is associated with many adverse health outcomes, and sit-stand workstations in offices have emerged as a way to counteract sedentary work. This paper reviews the existing knowledge on sit-stand workstations, treadmill workstations and bicycle workstations. The inclusion/exclusion criteria were: 1) empirical research examining the effectiveness of sit-stand workstations in lab or field studies, 2) working adult population, 3) sit-stand workstation interventions where workers performed the same task from a seated or standing position, 4) outcomes measures of discomfort (comfort), performance, sit-stand behaviors, user satisfaction, kinematic and physiological measures. Search terms were: sit-stand, treadmill, bicycle, workstations, sedentary behavior, office ergonomics, and comfort. Many studies considered productivity, comfort and physiological measures as important outcomes to assess the efficacy of sit-stand workstations and the experimental design was variable. Preliminary data suggests that some amount of standing during an 8-hour workday could be beneficial without compromising user comfort or productivity; however, there is very little data on the efficacy of treadmill and bicycle workstations. Based on these preliminary data from 26 studies, conducting large scale randomized controlled trials with ergonomic training as their essential component is recommended to understand the benefits of sit-stand workstations for prevention of sedentary work.

  8. How hepatitis C virus counteracts the interferon response: the jury is still out on NS5A.

    Science.gov (United States)

    Tan, S L; Katze, M G

    2001-05-25

    Interferons (IFNs) induce an antiviral state in the cell through complex and indirect mechanisms, which culminate in a direct inhibition of viral replication and stimulation of the host adaptive responses. Viruses often counteract with elaborate strategies to interfere with the induction as well as action of IFN effector molecules. This evolutionary battle between viruses and IFN components is a subject of intense research aimed at understanding the immunopathogenesis of viruses and the molecular basis of IFN signaling and action. In the case with hepatitis C virus (HCV), this may have profound implications for the therapeutic use of recombinant IFN in treating chronic hepatitis C. Depending on the subtype of HCV, current IFN-based treatment regimens are effective for only a small subset of chronic hepatitis C patients. Thus, one of the Holy Grails in HCV research is to understand the mechanisms by which the virus may evade IFN antiviral surveillance and establish persistent infection, which may eventually provide insights into new avenues for better antiviral therapy. Despite the lack of an efficient tissue culture system and an appropriate animal model for HCV infection, several mechanisms have been proposed based on clinical studies and in vitro experiments. This minireview focuses on the HCV NS5A nonstructural protein, which is implicated in playing a role in HCV tolerance to IFN treatment, possibly in part through its ability to inhibit the cellular IFN-induced PKR protein kinase.

  9. Severe hypofractionation: Non-homogeneous tumour dose delivery can counteract tumour hypoxia

    Energy Technology Data Exchange (ETDEWEB)

    Ruggieri, Ruggero; Naccarato, Stefania (Medical Physics Dept., Inst. Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, FC (Italy)), E-mail: ruggieri.ruggero@gmail.com; Nahum, Alan E. (Physics Dept., Clatterbridge Centre for Oncology, Bebington CH63 4JY (United Kingdom))

    2010-11-15

    Background. The current rationale for severely hypofractionated schedules (3-5 fractions) used in stereotactic-body-radiotherapy (SBRT) of non-small-cell lung cancer (NSCLC) is the small size of the irradiated volumes. Being the dose prescribed to the 60-80% isodose line enclosing the PTV, a non-homogeneous tumour-dose-delivery results which might impact on tumour hypoxia. A comparison between homogeneous and SBRT-like non-homogeneous tumour-dose-delivery is then proposed here, using severe hypofractionation on large tumour volumes where both dose prescription strategies are applicable. Materials and methods. For iso-NTCP hypofractionated schedules (1f/d5d/w) with respect to standard fractionation (d=2Gy), computed from the individual DVHs for lungs, oesophagus, heart and spinal cord (Lyman-Kutcher-Burman NTCP-model), TCP values were calculated (a-averaged Poissonian-LQ model) for homogeneous and SBRT-like non-homogeneous plans both with and without tumour hypoxia. Two different estimates of the oxygen-enhancement-ratio (OER) in combination with two distinct assumptions on the kinetics of reoxygenation were considered. Homogeneous and SBRT-like non-homogeneous plans were finally compared in terms of therapeutic ratio (TR), as the product of TCP and the four (1-NTCPi) values. Results. For severe hypofractionation (3-5 fractions) and for any of the hypotheses on the kinetics of reoxygenation and the OER, there was a significant difference between the computed TRs with or without inclusion of tumour hypoxia (anova, p=0.01) for homogeneous tumour-dose-delivery, but no significant difference for the SBRT-like non-homogeneous one. Further, a significantly increased mean TR for the group of SBRT-like non-homogeneous plans resulted (t-test, p=0.05) with respect to the group with homogeneous target-dose-coverage. Conclusions. SBRT-like dose-boosting seems to counterbalance the loss of reoxygenation within a few fractions. For SBRT it then seems that, in addition to the high

  10. Counteracting Hypertension with weightlessness?

    DEFF Research Database (Denmark)

    Norsk, Peter

    2008-01-01

    Many of us have been told to lose weight to lower our blood pressure, but going weightless? Studies of astronauts show that gravity does contribute to cardiovascular stress......Many of us have been told to lose weight to lower our blood pressure, but going weightless? Studies of astronauts show that gravity does contribute to cardiovascular stress...

  11. 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

  12. Botulinum neurotoxin type A counteracts neuropathic pain and facilitates functional recovery after peripheral nerve injury in animal models.

    Science.gov (United States)

    Marinelli, S; Luvisetto, S; Cobianchi, S; Makuch, W; Obara, I; Mezzaroma, E; Caruso, M; Straface, E; Przewlocka, B; Pavone, F

    2010-11-24

    A growing interest was recently focused on the use of Botulinum neurotoxin serotype A (BoNT/A) for fighting pain. The aim of this study was to investigate the effects of BoNT/A on neuropathic pain. It was observed that BoNT/A is able to counteract neuropathic pain induced by chronic constriction injury (CCI) to the sciatic nerve both in mice and in rats. This effect is already present after a single intraplantar (i.pl.) or intrathecal (i.t.) neurotoxin administration that significantly reduces the sciatic nerve ligation-induced mechanical allodynia in mice and rats and thermal hyperalgesia in rats. This effect was evident starting 24 h after the administration of BoNT/A and it was long-lasting, being present 81 or 25 days after i.pl. injection of the higher dose in mice (15 pg/paw) and rats (75 pg/paw), respectively, and 35 days after i.t. injection in rats (75 pg/rat). Moreover, BoNT/A-injected mice showed a quicker recovery of the walking pattern and weight bearing compared to control groups. The behavioral improvement was accompanied by structural modifications, as revealed by the expression of cell division cycle 2 (Cdc2) and growth associated protein 43 (GAP-43) regeneration associated proteins, investigated by immunofluorescence and Western blotting in the sciatic nerve, and by the immunofluorescence expression of S100β and glial fibrillary acidic protein (GFAP) Schwann cells proteins. In conclusion, the present research demonstrate long-lasting anti-allodynic and anti-hyperalgesic effects of BoNT/A in animal models of neuropathic pain together with an acceleration of regenerative processes in the injured nerve, as evidenced by both behavioral and immunohistochemistry/blotting analysis. These results may have important implications in the therapy of neuropathic pain.

  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

    2017-01-27

    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.

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

    Science.gov (United States)

    Aloui, Asma; Briki, Walid; Baklouti, Hana; Chtourou, Hamdi; Driss, Tarak; Chaouachi, Anis; Chamari, Karim; Souissi, Nizar

    2015-01-01

    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. 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. 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. 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.

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

    Directory of Open Access Journals (Sweden)

    Asma Aloui

    Full Text Available 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.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.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.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.

  16. The intestinotrophic peptide, GLP-2, counteracts the gastrointestinal atrophy in mice induced by the epidermal growth factor receptor inhibitor, erlotinib, and cisplatin

    DEFF Research Database (Denmark)

    Rasmussen, Andreas Rosén; Viby, Niels-Erik; Hare, Kristine Juul;

    2010-01-01

    Erlotinib, an epidermal-growth-factor receptor inhibitor, belongs to a new generation of targeted cancer therapeutics. Gastrointestinal side-effects are common and have been markedly aggravated when erlotinib is combined with cytostatics. We examined the effects of erlotinib alone and combined wi...... with the cytostatic, cisplatin, on the gastrointestinal tract and examined whether glucagon-like peptide-2 (GLP-2), an intestinal hormone with potent intestinotrophic properties, might counteract the possible damaging effects of the treatments....

  17. IL-17 attenuates the anti-apoptotic effects of GM-CSF in human neutrophils.

    Science.gov (United States)

    Dragon, Stéphane; Saffar, Arash Shoja; Shan, Lianyu; Gounni, Abdelilah Soussi

    2008-01-01

    Interleukin (IL)-17A is a pleiotropic, pro-inflammatory cytokine that is implicated in chronic inflammatory and degenerative disorders. IL-17 has been demonstrated to link activated T-lymphocyte with the recruitment of neutrophils at sites of inflammation, however whether IL-17 can mediate neutrophil survival and subsequently affect inflammatory responses has not fully been elucidated. In our study, we demonstrate that human peripheral blood and HL-60 differentiated neutrophils express mRNA and cell surface IL-17A receptor. IL-17A does not affect the rate of spontaneous neutrophil apoptosis, however significantly decreased granulocyte macrophage-colony stimulating factor (GM-CSF)-mediated survival by antagonizing the signal transduction pathways of p38, Erk1/2 and signal transducer and activator of transcription (STAT) 5B. These events were associated with reduced myeloid cell lymphoma-1 (Mcl-1) protein levels, increased translocation and aggregation of Bax to mitochondria, decreased mitochondrial transmembrane potential and in an increase in caspase-3/7 activity. These events were independent of increased Fas or soluble Fas ligand expression levels. Taken together, our findings suggest that IL-17 may regulate neutrophil homeostasis and favor the resolution of inflamed tissues by attenuating the delay in neutrophil apoptosis induced by inflammatory cytokines.

  18. Pharmacological strategies to counteract antipsychotic-induced weight gain and metabolic adverse effects in schizophrenia: a systematic review and meta-analysis.

    Science.gov (United States)

    Mizuno, Yuya; Suzuki, Takefumi; Nakagawa, Atsuo; Yoshida, Kazunari; Mimura, Masaru; Fleischhacker, Walter Wolfgang; Uchida, Hiroyuki

    2014-11-01

    Antipsychotic-induced metabolic adversities are often difficult to manage. Using concomitant medications to counteract these adversities may be a rational option. To systematically determine the effectiveness of medications to counteract antipsychotic-induced metabolic adversities in patients with schizophrenia. Published articles until November 2013 were searched using 5 electronic databases. Clinical trial registries were searched for unpublished trials. Double-blind randomized placebo-controlled trials focusing on patients with schizophrenia were included if they evaluated the effects of concomitant medications on antipsychotic-induced metabolic adversities as a primary outcome. Variables relating to participants, interventions, comparisons, outcomes, and study design were extracted. The primary outcome was change in body weight. Secondary outcomes included clinically relevant weight change, fasting glucose, hemoglobin A1c, fasting insulin, insulin resistance, cholesterol, and triglycerides. Forty trials representing 19 unique interventions were included in this meta-analysis. Metformin was the most extensively studied drug in regard to body weight, the mean difference amounting to -3.17 kg (95% CI: -4.44 to -1.90 kg) compared to placebo. Pooled effects for topiramate, sibutramine, aripiprazole, and reboxetine were also different from placebo. Furthermore, metformin and rosiglitazone improved insulin resistance, while aripiprazole, metformin, and sibutramine decreased blood lipids. When nonpharmacological strategies alone are insufficient, and switching antipsychotics to relatively weight-neutral agents is not feasible, the literature supports the use of concomitant metformin as first choice among pharmacological interventions to counteract antipsychotic-induced weight gain and other metabolic adversities in schizophrenia. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For

  19. Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue

    Directory of Open Access Journals (Sweden)

    Specht Anke

    2010-01-01

    Full Text Available Abstract Background The human immunodeficiency virus type 1 (HIV-1 Vpu protein degrades CD4 and counteracts a restriction factor termed tetherin (CD317; Bst-2 to enhance virion release. It has been suggested that both functions can be genetically separated by mutation of a serine residue at position 52. However, recent data suggest that the S52 phosphorylation site is also important for the ability of Vpu to counteract tetherin. To clarify this issue, we performed a comprehensive analysis of HIV-1 with a mutated casein kinase-II phosphorylation site in Vpu in various cell lines, primary blood lymphocytes (PBL, monocyte-derived macrophages (MDM and ex vivo human lymphoid tissue (HLT. Results We show that mutation of serine 52 to alanine (S52A entirely disrupts Vpu-mediated degradation of CD4 and strongly impairs its ability to antagonize tetherin. Furthermore, casein-kinase II inhibitors blocked the ability of Vpu to degrade tetherin. Overall, Vpu S52A could only overcome low levels of tetherin, and its activity decreased in a manner dependent on the amount of transiently or endogenously expressed tetherin. As a consequence, the S52A Vpu mutant virus was unable to replicate in macrophages, which express high levels of this restriction factor. In contrast, HIV-1 Vpu S52A caused CD4+ T-cell depletion and spread efficiently in ex vivo human lymphoid tissue and PBL, most likely because these cells express comparably low levels of tetherin. Conclusion Our data explain why the effect of the S52A mutation in Vpu on virus release is cell-type dependent and suggest that a reduced ability of Vpu to counteract tetherin impairs HIV-1 replication in macrophages, but not in tissue CD4+ T cells.

  20. What patients do to counteract the symptoms of Willis-Ekbom disease (RLS/WED: Effect of gender and severity of illness

    Directory of Open Access Journals (Sweden)

    Ravi Gupta

    2014-01-01

    Full Text Available Objectives: This study was carried out to assess different counteracting strategies used by patients with idiopathic Willis-Ekbom disease (RLS/WED. Whether these strategies were influenced by gender or disease severity was also assessed. Materials and Methods: A total of 173 patients of idiopathic RLS/WED were included in this study. Their demographic data was recorded. Details regarding the RLS/WED and strategies that they used to counteract the symptoms were asked. The severity of RLS/WED was measured with the help of the Hindi version of international restless legs syndrome severity rating scale. They were asked to provide the details regarding the relief obtained from all the strategies they used on three-point scale: no relief, some relief, and complete relief. Results: Of the patients, 72% were females. Mean age of the subjects in this study was 39.6 ± 12.6 years, and male subjects were older than females. Four common strategies were reported by the patients to counter the sensations of RLS/WED: moving legs while in bed (85.5%, asking somebody to massage their legs or massaging legs themselves (76.9%, walking (53.2%, and tying a cloth/rope tightly on the legs (39.3%. Of all the patients who moved their legs, 6.7% did not experience any relief, 64.2% reported some relief, and 28.4% reported complete relief. Similarly, of all the patients who used "walking" to counteract symptoms, 50% reported complete relief, 44.5% reported some relief, and the rest did not experience any relief. Many of these patients reported that massage and tying a cloth/rope on legs brought greater relief than any of these strategies. Tying cloth on the leg was more common among females as compared to males (45.9% females vs. 23.5% males; χ2 = 7.54; P = 0.006, while patients with moderately severe to severe RLS/WED reported "moving legs in bed" (79.3% in mild to moderate RLS/WED; 91.8% in severe to very severe RLS; χ2 = 5.36; P = 0.02. Conclusion: Patients with RLS

  1. What patients do to counteract the symptoms of Willis-Ekbom disease (RLS/WED): Effect of gender and severity of illness.

    Science.gov (United States)

    Gupta, Ravi; Goel, Deepak; Ahmed, Sohaib; Dhar, Minakshi; Lahan, Vivekananda

    2014-10-01

    This study was carried out to assess different counteracting strategies used by patients with idiopathic Willis-Ekbom disease (RLS/WED). Whether these strategies were influenced by gender or disease severity was also assessed. A total of 173 patients of idiopathic RLS/WED were included in this study. Their demographic data was recorded. Details regarding the RLS/WED and strategies that they used to counteract the symptoms were asked. The severity of RLS/WED was measured with the help of the Hindi version of international restless legs syndrome severity rating scale. They were asked to provide the details regarding the relief obtained from all the strategies they used on three-point scale: no relief, some relief, and complete relief. Of the patients, 72% were females. Mean age of the subjects in this study was 39.6 ± 12.6 years, and male subjects were older than females. Four common strategies were reported by the patients to counter the sensations of RLS/WED: moving legs while in bed (85.5%), asking somebody to massage their legs or massaging legs themselves (76.9%), walking (53.2%), and tying a cloth/rope tightly on the legs (39.3%). Of all the patients who moved their legs, 6.7% did not experience any relief, 64.2% reported some relief, and 28.4% reported complete relief. Similarly, of all the patients who used "walking" to counteract symptoms, 50% reported complete relief, 44.5% reported some relief, and the rest did not experience any relief. Many of these patients reported that massage and tying a cloth/rope on legs brought greater relief than any of these strategies. Tying cloth on the leg was more common among females as compared to males (45.9% females vs. 23.5% males; χ(2) = 7.54; P = 0.006), while patients with moderately severe to severe RLS/WED reported "moving legs in bed" (79.3% in mild to moderate RLS/WED; 91.8% in severe to very severe RLS; χ(2) = 5.36; P = 0.02). Patients with RLS/WED use a variety of strategies to counteract symptoms. These

  2. Efficacy and safety/toxicity study of recombinant vaccinia virus JX-594 in two immunocompetent animal models of glioma.

    Science.gov (United States)

    Lun, XueQing; Chan, Jennifer; Zhou, Hongyuan; Sun, Beichen; Kelly, John J P; Stechishin, Owen Owen; Bell, John C; Parato, Kelley; Hu, Kang; Vaillant, Dominique; Wang, Jiahu; Liu, Ta-Chiang; Breitbach, Caroline; Kirn, David; Senger, Donna L; Forsyth, Peter A

    2010-11-01

    The purpose of this study was to investigate the oncolytic potential of the recombinant, granulocyte macrophage colony-stimulating factor (GM-CSF)-expressing vaccinia virus (VV) JX-594 in experimental malignant glioma (MGs) in vitro and in immunocompetent rodent models. We have found that JX-594 killed all MG cell lines tested in vitro. Intratumoral (i.t.) administration of JX-594 significantly inhibited tumor growth and prolonged survival in rats-bearing RG2 intracranial (i.c.) tumors and mice-bearing GL261 brain tumors. Combination therapy with JX-594 and rapamycin significantly increased viral replication and further prolonged survival in both immunocompetent i.c. MG models with several animals considered "cured" (three out of seven rats >120 days, terminated experiment). JX-594 infected and killed brain tumor-initiating cells (BTICs) from patient samples grown ex vivo, and did so more efficiently than other oncolytic viruses MYXV, Reovirus type-3, and VSV(ΔM51). Additional safety/toxicity studies in nontumor-bearing rodents treated with a supratherapeutic dose of JX-594 demonstrated GM-CSF-dependent inflammation and necrosis. These results suggest that i.c. administered JX-594 triggers a predictable GM-CSF-mediated inflammation in murine models. Before proceeding to clinical trials, JX-594 should be evaluated in the brains of nonhuman primates and optimized for the viral doses, delivery routes as well as the combination agents (e.g., mTOR inhibitors).

  3. 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.

  4. 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.

  5. Mescaline-induced changes of brain-cortex ribosomes. Role of sperimidine in counteracting the destabilizing effect of mescaline of brain-cortex ribosomes.

    Science.gov (United States)

    Datta, R K; Antopol, W; Ghosh, J J

    1971-11-01

    1. The effect of spermidine on the mescaline-induced changes of brain-cortex ribosomes was studied by adding spermidine during the treatment of goat brain-cortex slices with mescaline. 2. Mescaline treatment of brain-cortex slices removed a portion of the endogenous spermidine from ribosomes and this removal was significantly prevented when spermidine was present during mescaline treatment. 3. Spermidine present during mescaline treatment of brain-cortex slices counteracted, to some extent, the destabilizing effect of mescaline on ribosomes with respect to heat denaturation. 4. Mescaline treatment of brain-cortex slices made ribosomes more susceptible to breakdown, releasing protein and RNA, and resulting in loss of ribosomal enzymic activities. However, spermidine present during mescaline treatment counteracted moderately the mescaline-induced ribosomal susceptibility to breakdown and ribosomal loss of enzymic activities. 5. Ribosomes of mescaline-treated cortex slices were rapidly degraded by ribonuclease and trypsin. However, if spermidine was present during mescaline treatment of brain-cortex slices the rates of degradation diminished.

  6. The Deubiquitinase USP47 Stabilizes MAPK by Counteracting the Function of the N-end Rule ligase POE/UBR4 in Drosophila.

    Science.gov (United States)

    Ashton-Beaucage, Dariel; Lemieux, Caroline; Udell, Christian M; Sahmi, Malha; Rochette, Samuel; Therrien, Marc

    2016-08-01

    RAS-induced MAPK signaling is a central driver of the cell proliferation apparatus. Disruption of this pathway is widely observed in cancer and other pathologies. Consequently, considerable effort has been devoted to understanding the mechanistic aspects of RAS-MAPK signal transmission and regulation. While much information has been garnered on the steps leading up to the activation and inactivation of core pathway components, comparatively little is known on the mechanisms controlling their expression and turnover. We recently identified several factors that dictate Drosophila MAPK levels. Here, we describe the function of one of these, the deubiquitinase (DUB) USP47. We found that USP47 acts post-translationally to counteract a proteasome-mediated event that reduces MAPK half-life and thereby dampens signaling output. Using an RNAi-based genetic interaction screening strategy, we identified UBC6, POE/UBR4, and UFD4, respectively, as E2 and E3 enzymes that oppose USP47 activity. Further characterization of POE-associated factors uncovered KCMF1 as another key component modulating MAPK levels. Together, these results identify a novel protein degradation module that governs MAPK levels. Given the role of UBR4 as an N-recognin ubiquitin ligase, our findings suggest that RAS-MAPK signaling in Drosophila is controlled by the N-end rule pathway and that USP47 counteracts its activity.

  7. The influence of the time of antidotal treatment administration on the potency of newly developed oximes to counteract acute toxic effects of tabun in mice.

    Science.gov (United States)

    Kassa, Jirí

    2005-01-01

    (1) The influence of the time of administration of antidotal treatment consisting of anticholinergic drug (atropine) and newly developed oxime (K027 or K048) on its effectiveness to eliminate tabun-induced lethal toxic effects was studied in mice. (2) The therapeutic efficacy of antidotal treatment of tabun-induced acute poisoning depends on the time of its administration regardless of the choice of the oxime. (3) Our results show that both oximes studied (K027, K048) are able to sufficiently eliminate lethal effects of tabun. Nevertheless, their efficacy significantly decreases when they were administered 5 min after tabun poisoning. (4) The findings support the hypothesis that both newly developed oximes appear to be suitable oximes to counteract acute toxicity of tabun although their ability to eliminate lethal toxic effects of tabun significantly decreases with prolonged time interval between tabun challenge and antidotal treatment administration.

  8. 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...

  9. Toxin-antitoxin loci as stress-response-elements: ChpAK/MazF and ChpBK cleave translated RNAs and are counteracted by tmRNA

    DEFF Research Database (Denmark)

    Christensen, S.K.; Pedersen, K.; Hansen, Flemming G.

    2003-01-01

    Prokaryotic chromosomes encode toxin-antitoxin loci, often in multiple copies. In most cases, the function of these genes is not known. The chpA (mazEF) locus of Escherichia coli has been described as a cell killing module that induces bacterial apoptosis during nutritional stress. However, we...... found recently that ChpAK (MazF) does not confer cell killing but rather, induces a bacteriostatic condition from which the cells could be resuscitated. Results presented here yield a mechanistic explanation for the detrimental effect on cell growth exerted by ChpAK and the homologous ChpBK protein of E....... coli. We show that both proteins inhibit translation by inducing cleavage of translated mRNAs. Consistently, the inhibitory effect of the proteins was counteracted by tmRNA. Amino acid starvation induced strong transcription of chpA that depended on Lon protease but not on ppGpp. Simultaneously, Chp...

  10. 水下激光目标的统计对消分割法%Target Segmentation from Laser Underwater Images Based on Statistic Counteraction

    Institute of Scientific and Technical Information of China (English)

    费佩燕; 郭宝龙; 章正宇

    2004-01-01

    The recognition of laser underwater target is a new disquisitive field, in which many problems are open, and segmentation is the key problem. To recognize underwater target,segmentation must be performed efficiently because there is a lot of speckle noise in laser underwater images. According to the principle that noise with identically statistic characteristics can counteract noise in images, a new algorithm called target segmentation from laser underwater image based on statistic counteraction is proposed to remove speckle noise and extract targets with wavelet transform and statistics. Experiments demonstrate that this method is efficient and feasible.%水下激光目标的识别是一个崭新的研究领域,有许多问题需要解决,其中,目标分割是关键.水下激光图像中夹杂着严重的散斑噪声,受其影响,要识别水下激光目标,就要对图像进行有效的消噪,然后进行目标分割.本文依据具有相似统计特征的噪声可抵消图像中的相应噪声这一基理,结合小波变换和统计法,提出了一种水下激光目标的统计对消分割法,以去除噪声,提取目标.实验结果表明该方法是有效可行的.

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Pablo eGaleano

    2015-01-01

    Full Text Available 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.

  13. 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

    2015-01-01

    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. PMID:25601829

  14. Stable gastric pentadecapeptide BPC 157 heals cysteamine-colitis and colon-colon-anastomosis and counteracts cuprizone brain injuries and motor disability.

    Science.gov (United States)

    Klicek, R; Kolenc, D; Suran, J; Drmic, D; Brcic, L; Aralica, G; Sever, M; Holjevac, J; Radic, B; Turudic, T; Kokot, A; Patrlj, L; Rucman, R; Seiwerth, S; Sikiric, P

    2013-10-01

    Stable gastric pentadecapeptide BPC 157 was suggested to link inflammatory bowel disease and multiple sclerosis, and thereby, shown to equally counteract the models of both of those diseases. For colitis, cysteamine (400 mg/kg intrarectally (1 ml/rat)) and colon-colon anastomosis (sacrifice at day 3, 5, 7, and 14) were used. BPC 157 (10 μg/kg, 10 ng/kg) was applied either intraperitoneally once time daily (first application immediately after surgery, last at 24 hours before sacrifice) or per-orally in drinking water (0.16 μg/ml/12 ml/day till the sacrifice) while controls simultaneously received an equivolume of saline (5 ml/kg) intraperitoneally or drinking water only (12 ml/day). A multiple sclerosis suited toxic rat model, cuprizone (compared with standard, a several times higher regimen, 2.5% of diet regimen + 1 g/kg intragastrically/day) was combined with BPC 157 (in drinking water 0.16 μg or 0.16 ng/ml/12 ml/day/rat + 10 μg or 10 ng/kg intragastrically/day) till the sacrifice at day 4. In general, the controls could not heal cysteamine colitis and colon-colon anastomosis. BPC 157 induced an efficient healing of both at the same time. Likewise, cuprizone-controls clearly exhibited an exaggerated and accelerated damaging process; nerve damage appeared in various brain areas, with most prominent damage in corpus callosum, laterodorsal thalamus, nucleus reunions, anterior horn motor neurons. BPC 157-cuprizone rats had consistently less nerve damage in all damaged areas, especially in those areas that otherwise were most affected. Consistently, BPC 157 counteracted cerebellar ataxia and impaired forelimb function. Thereby, this experimental evidence advocates BPC 157 in both inflammatory bowel disease and multiple sclerosis therapy.

  15. 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....... 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...... biomass, whereas drought significantly reduced it. Elevated temperature did not result in any detectable effects. No interactions between the three factors were observed. Interestingly, the positive effect of increased CO2 and the negative effect of drought were cancelled out when applied in combination...

  16. Berberine increases adipose triglyceride lipase in 3T3-L1 adipocytes through the AMPK pathway

    OpenAIRE

    Jiang, Dongqing; Wang, Dianhui; ZHUANG, XIANGHUA; Wang, Zhanqing; Ni, Yihong; Chen, Shihong; Sun, Fudun

    2016-01-01

    Background Obesity is closely related to the metabolism of triacylglycerol (TG) in adipocytes. Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are rate-limiting enzymes that control the hydrolysis of TG. Effects on ATGL and HSL to increase lipolysis may counteract obesity. Berberine (BBR) is a compound derived from the Chinese medicine plant Coptis chinensis. In the present study we show the effects of BBR on ATGL and HSL and explore the potential underlying mechanisms o...

  17. Adaptive Optics to Counteract Thermal Aberrations: System Design for EUV-Lithography with Sub-nm Precision

    NARCIS (Netherlands)

    Saathof, R.

    2013-01-01

    In highly precise systems the thermal expansion of system-parts is of increasing concern, since it can severely compromise its performance at sub-nanometre level. An example of such a system is an Extreme UltraViolet (EUV)-lithography machine that is used in the semi-conductor industry to project th

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

    NARCIS (Netherlands)

    van Heumen, Bjorn W. H.; Roelofs, Hennie M. J.; Vink-Borger, M. Elisa; Dekker, Evelien; Mathus-Vliegen, Elisabeth M. H.; Dees, Jan; Koornstra, Jan J.; Langers, Alexandra M. J.; Nagtegaal, Iris D.; Kampman, Ellen; Peters, Wilbert H. M.; Nagengast, Fokko M.

    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 car

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

    NARCIS (Netherlands)

    Heumen, van B.W.; Roelofs, H.M.J.; Vink-Börger, M.E.; Dekker, E.; Mathus-Vliegen, E.M.; Dees, J.; Koornstra, J.J.; Langers, A.M.; Nagtegaal, I.D.; Kampman, E.; Peters, W.H.; Nagengast, F.M.

    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 card

  20. Adaptive Optics to Counteract Thermal Aberrations: System Design for EUV-Lithography with Sub-nm Precision

    NARCIS (Netherlands)

    Saathof, R.

    2013-01-01

    In highly precise systems the thermal expansion of system-parts is of increasing concern, since it can severely compromise its performance at sub-nanometre level. An example of such a system is an Extreme UltraViolet (EUV)-lithography machine that is used in the semi-conductor industry to project th

  1. Counteraction of the Antiapoptotic Protein Survivin by Diverting Expression to its Proapoptotic Splice Variant Survivin-2B

    Science.gov (United States)

    2010-01-01

    negatively regulated by low glucose. [17] Further, glucose restriction activates the longevity- associated histone and protein deacetylase, SIRT1 ...pattern of decreasing with low glucose. We also studied SIRT1 because it was already reported to epigenetically silence survivin transcription and...furthermore to be upregulated during glucose restriction. Indeed, SIRT1 increased with glucose restriction, in opposite manner as survivin and survivin-2B

  2. Alteration of hepatic cells glucose metabolism as a non-cholinergic detoxication mechanism in counteracting diazinon-induced oxidative stress.

    Science.gov (United States)

    Teimouri, Fatemeh; Amirkabirian, Nasim; Esmaily, Hadi; Mohammadirad, Azadeh; Aliahmadi, Atousa; Abdollahi, Mohammad

    2006-12-01

    The aim of this study was to evaluate effects of acute exposure to various doses of diazinon, a widely used synthetic organophosphorus (OP) insecticide on plasma glucose, hepatic cells key enzymes of glycogenolysis and gluconeogenesis, and oxidative stress in rats. Diazinon was administered by gavage at doses of 15, 30 and 60 mg/ kg. The liver was perfused and removed under anaesthesia. The activities of glycogen phosphorylase (GP), phosphoenolpyruvate carboxykinase (PEPCK), thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) were analysed in liver homogenate. Administration of diazinon (15, 30 and 60 mg/kg) increased plasma glucose concentrations by 101.43% (P = 0.001), 103.68% (P = 0.000) and 160.65% (P = 0.000) of control, respectively. Diazinon (15, 30 and 60 mg/kg) increased hepatic GP activity by 43.5% (P = 0.05), 70.3% (P = 0.00) and 117.2% (P = 0.02) of control, respectively. In addition, diazinon (30 and 60 mg/kg) increased hepatic PEPCK by 77.3% (P = 0.000) and 93.5% (P = 0.000) of control, respectively. Diazinon (30 and 60 mg/kg) decreased liver TAC by 38% (P = 0.046) and 48% (P = 0.000) of control, respectively. Also diazinon (30 and 60 mg/kg) increased hepatic cell liver lipid peroxidation by 77% (P = 0.05) and 280% (P = 0.000) of control. The correlations between plasma glucose and hepatic cells TBARS (r2 = 0.537, P = 0.02), between plasma glucose and ChE activity (r2 = 0.81, P = 0.049) and between plasma glucose and hepatic cells GP activity (r2 = 0.833, P = 0.04) were significant. It is concluded that the liver cells are a site of toxic action of diazinon. Diazinon increases glucose release from liver into blood through activation of glycogenolysis and gluconeogenesis as a detoxication non-cholinergic mechanism to overwhelm diazinon-induced toxic stress. The results are in accordance with the hypothesis that OPs are a predisposing factor of diabetes.

  3. 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.

  4. Downregulation of Noxa by RAF/MEK inhibition counteracts cell death response in mutant B-RAF melanoma cells.

    Science.gov (United States)

    Basile, Kevin J; Aplin, Andrew E

    2012-01-01

    FDA approval of new therapies in 2011 has greatly expanded the treatment options for metastatic melanoma. Patients with V600 mutant v-raf murine sarcoma viral oncogene homolog B1 (B-RAF) positive metastatic melanoma are now treated with the RAF inhibitor, vemurafenib (Zelboraf) as a first line therapy. Vemurafenib decreases tumor size by at least 30% in approximately 50% of patients and increases progression-free survival and overall patient survival compared to the previous standard-of-care, dacarbazine. However, some patients treated with vemurafenib fail to show significant tumor shrinkage, and most patients who initially respond to the drug eventually show disease progression. Therefore, there is a clinical need to improve efficacy and prevent resistance to vemurafenib. It has been previously shown that cell death resulting from RAF/mitogen-activated protein kinase kinase (MEK) inhibition is largely dependent on increased expression of pro-apoptotic, Bcl-2 homology domain (BH3)-only proteins, such as Bcl-2-like 11 (Bim-EL) and Bcl-2 modifying factor (Bmf). Here, we show that contrary to expression of Bim-EL and Bmf, the pro-apoptotic, BH3-only protein, phorbol-12-myristate-13-acetate-induced protein 1 (Noxa), is strongly downregulated after RAF/MEK inhibition. This downregulation occurs at both the protein and mRNA level of expression and is associated with the inhibition of cell cycle progression. Restoring expression of Noxa in combination with RAF/MEK inhibition enhances cell death. Co-expression of the pro-survival, B-cell CLL/lymphoma 2 (Bcl-2) family member, myeloid cell leukemia sequence 1 (Mcl-1), with Noxa fully mitigates the enhanced cell death associated with increased Noxa expression. These data indicate that manipulating the Noxa/Mcl-1 axis may enhance the efficacy of RAF/MEK inhibitors.

  5. 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

    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 of gr....... However, this may only be a temporary solution that will have to be supplemented by increased reintegration with the sea and managed retreat of seawalls or near-coastal agricultural areas to effectively safeguard the future salt marsh biome....

  6. An important role of interleukin-10 in counteracting excessive immune response in HT-29 cells exposed to Clostridium butyricum

    Directory of Open Access Journals (Sweden)

    Gao Quanxin

    2012-06-01

    Full Text Available Abstract Background Clostridium butyricum has become increasingly important in preventing and treating intestinal inflammation. In the intestine it may increase the resistance of the gut to pathogen invasion via inducing the secretion of anti-inflammatory cytokines. Interleukin 10 (IL-10 plays a central role in preventing certain inflammatory diseases by down-regulating inflammatory cascades. In a previous study, we observed that the level of IL-10 mRNA was modulated by C. butyricum. The aim of this study was to investigate whether C. butyricum achieves its beneficial effects through IL-10. Results We treated HT-29 cells with anti-IL-10 (IL-10 antibody or siIL-10 (IL-10 small interfering RNA to disrupt IL-10. In both cases, the effects of C. butyricum-induced NF-κB activation and IL-8 expression were enhanced. We also found that neutralization or knockdown of IL-10 could induce apoptosis and necrosis of HT-29 cells treated with C. butyricum compared with control cells. Conclusions These findings show that IL-10 serves an important role in C. butyricum-mediated immune protection, and in host recognition of C. butyricum.

  7. PTH (1–34), but not strontium ranelate counteract loss of trabecular thickness and bone strength in disuse osteopenic rats

    DEFF Research Database (Denmark)

    Brüel, Annemarie; Vegger, Jens Bay; Raffalt, Anders Christer;

    2013-01-01

    +PTH+SrR (n=12 in each group). PTH was given as injections (SC) at a dosage of 60 μg/kg/d, and SrR as 900 mg/kg/d in the diet. The experiment lasted for 4weeks.BTX resulted in lower trabecular bone formation rate (−68%) and periosteal bone formation rate (−91%), and a higher fraction of osteoclast......) and periosteal (5-fold increase vs. BTX) bone formation rate, trabecular thickness (+25% vs. BTX) and femoral neck strength (+24% vs. BTX). In contrast, SrR did not influence BTX-induced loss of bone formation rate, trabecular bone volume fraction, trabecular thickness, or bone strength. Finally, no additive...

  8. The intestinotrophic peptide, glp-2, counteracts intestinal atrophy in mice induced by the epidermal growth factor receptor inhibitor, gefitinib

    DEFF Research Database (Denmark)

    Hare, Kristine Juul; Hartmann, Bolette; Kissow, Hannelouise;

    2007-01-01

    PURPOSE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have been introduced as antitumor agents in the treatment of cancers overexpressing the receptor. The treatment has gastrointestinal side effects which may decrease patient compliance and limit the efficacy. Glucagon...... and cross-sectional area were decreased. The same parameters were increased by GLP-2 treatment alone, and when GLP-2 was combined with the gefitinib treatment, the parameters remained unchanged. CONCLUSIONS: Treatment with an EGFR tyrosine kinase inhibitor in mice results in small-intestinal growth...... inhibition that can be completely prevented by simultaneous treatment with GLP-2. This suggests that the gastrointestinal side effects elicited by treatment with EGFR tyrosine kinase inhibitors can be circumvented by GLP-2 treatment....

  9. 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.

  10. 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 CCl4 -caused hepatic fibrosis and portal hypertension. Immunofluorescence staining visually showed a decrease in FXR expression in CCl4 -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 CCl4 -induced liver injury. DHA also reduced CCl4 -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.

  11. 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

  12. Autophagy counteracts apoptosis in human multiple myeloma cells exposed to oridonin in vitro via regulating intracellular ROS and SIRT1

    Institute of Scientific and Technical Information of China (English)

    Rong ZENG; Yan CHEN; Shuai ZHAO; Guo-hui CUI

    2012-01-01

    To explore the mechanisms underlying the oridonin-induced apoptosis and autophagy in human multiple myeloma cells in vitro.Methods:Human multiple myeloma RPMI8266 cells were used.The cell viability was assessed using MTT assay.Morphological changes of apoptosis and autophagy were observed under transmission electron microscope.TUNEL and annexin V-FITC/PI dual staining assays were used to measure apoptosis.Autophagy was analyzed using Western blot analysis and immunofluorescence staining with a QDs605 nm-Anti-LC3 fluorescent probe.Intracellular ROS was estimated with flow cytometry using DCFH-DA fluorescent probe.Protein levels of active caspase 3,Beclin 1 and SIRT1 were determined with Western blot analysis.Results:Exposure to oridonin (1-64 μmol/L) inhibited the proliferation of RPMI8266 cells in a concentration-dependent manner with an IC50 value of 6.74 μmol/L.Exposure to oridonin (7 μmol/L) simultaneously induced caspase 3-mediated apoptosis and Beclin 1-dependent autophagy of RPMI8266 cells.Both the apoptosis and autophagy were time-dependent,and apoptosis was the main effector pathway of cell death.Exposure to oridonin (7 μmol/L) increased intracellular ROS and reduced SIRT1 nuclear protein in a time-dependent manner.The blockade of intracellular generation of ROS by NAC (5 mmol/L) abrogated apoptosis,autophagy and the decrease of SIRT1 in the cells exposed to oridonin (7 μmol/L).The inhibition of autophagy by 3-MA (5 mmol/L) sensitized the cells to oridonin-induced apoptosis,which was accompanied by increased intracellular ROS and decreased SlRT1.Conclusion:Oridonin simultaneously induces apoptosis and autophagy of human multiple myeloma RPMI8266 cells via regulation of intracellular ROS generation and SIRT1 nuclear protein.The cytotoxicity of oridonin is mainly mediated through the apoptotic pathway,whereas the autophagy protects the cells from apoptosis.

  13. Buddy-to-Buddy, a citizen soldier peer support program to counteract stigma, PTSD, depression, and suicide.

    Science.gov (United States)

    Greden, John F; Valenstein, Marcia; Spinner, Jane; Blow, Adrian; Gorman, Lisa A; Dalack, Gregory W; Marcus, Sheila; Kees, Michelle

    2010-10-01

    Citizen soldiers (National Guard and Reserves) represent approximately 40% of the two million armed forces deployed to Afghanistan and Iraq. Twenty-five to forty percent of them develop PTSD, clinical depression, sleep disturbances, or suicidal thoughts. Upon returning home, many encounter additional stresses and hurdles to obtaining care: specifically, many civilian communities lack military medical/psychiatric facilities; financial, job, home, and relationship stresses have evolved or have been exacerbated during deployment; uncertainty has increased related to future deployment; there is loss of contact with military peers; and there is reluctance to recognize and acknowledge mental health needs that interfere with treatment entry and adherence. Approximately half of those needing help are not receiving it. To address this constellation of issues, a private-public partnership was formed under the auspices of the Welcome Back Veterans Initiative. In Michigan, the Army National Guard teamed with the University of Michigan and Michigan State University to develop innovative peer-to-peer programs for soldiers (Buddy-to-Buddy) and augmented programs for military families. Goals are to improve treatment entry, adherence, clinical outcomes, and to reduce suicides. This manuscript describes training approaches, preliminary results, and explores future national dissemination.

  14. The Base Excision Repair system of Salmonella enterica serovar typhimurium counteracts DNA damage by host nitric oxide.

    Directory of Open Access Journals (Sweden)

    Anthony R Richardson

    2009-05-01

    Full Text Available Intracellular pathogens must withstand nitric oxide (NO. generated by host phagocytes. Salmonella enterica serovar Typhimurium interferes with intracellular trafficking of inducible nitric oxide synthase (iNOS and possesses multiple systems to detoxify NO.. Consequently, the level of NO. stress encountered by S. Typhimurium during infection in vivo has been unknown. The Base Excision Repair (BER system recognizes and repairs damaged DNA bases including cytosine and guanine residues modified by reactive nitrogen species. Apurinic/apyrimidinic (AP sites generated by BER glycosylases require subsequent processing by AP endonucleases. S. Typhimurium xth nfo mutants lacking AP endonuclease activity exhibit increased NO. sensitivity resulting from chromosomal fragmentation at unprocessed AP sites. BER mutant strains were thus used to probe the nature and extent of nitrosative damage sustained by intracellular bacteria during infection. Here we show that an xth nfo S. Typhimurium mutant is attenuated for virulence in C3H/HeN mice, and virulence can be completely restored by the iNOS inhibitor L-NIL. Inactivation of the ung or fpg glycosylase genes partially restores virulence to xth nfo mutant S. Typhimurium, demonstrating that NO. fluxes in vivo are sufficient to modify cytosine and guanine bases, respectively. Mutants lacking ung or fpg exhibit NO.-dependent hypermutability during infection, underscoring the importance of BER in protecting Salmonella from the genotoxic effects of host NO.. These observations demonstrate that host-derived NO. damages Salmonella DNA in vivo, and the BER system is required to maintain bacterial genomic integrity.

  15. The role of a high pull headgear in counteracting side effects from intrusion of the maxillary anterior segment.

    Science.gov (United States)

    van Steenbergen, E; Burstone, C J; Prahl-Andersen, B; Aartman, I H A

    2004-08-01

    Intrusion of incisors is often the preferred treatment of a deep overbite. This study focuses on deep overbite correction by intrusion of maxillary incisors. The purpose of this study is to determine whether high-pull headgear wear can prevent steepening of the buccal segment, extrusion of the buccal segment, maintain arch width, and increase the rate of incisor intrusion. The number of patients needed for this study was calculated to be 20. Patients were between nine and 14 years of age and assigned to one of two groups. In each group, intrusion of maxillary incisors was performed. Patients in one group wore a high-pull headgear at night, and patients in the other group did not. For each patient, a lateral head film, impressions with a wax bite in centric occlusion, and intraoral photographs were taken at the beginning and end of intrusion. This study demonstrated that high-pull headgear had no effect on steepening and extrusion of the buccal segments or on the rate of intrusion but did have an effect on narrowing of the buccal segments. By performing intrusion as described in this study, no statistically significant side effects were observed in the buccal segments, whereas a statistically significant amount of incisor intrusion of 2.24 mm in the no-headgear group and 2.37 mm in the headgear group was observed.

  16. 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.

  17. The pharmacology of neurotrophic treatment with Cerebrolysin: brain protection and repair to counteract pathologies of acute and chronic neurological disorders.

    Science.gov (United States)

    Masliah, E; Díez-Tejedor, E

    2012-04-01

    Neurotrophic factors are considered as part of the therapeutic strategy for neurological disorders like dementia, stroke and traumatic brain injury. Cerebrolysin is a neuropeptide preparation which mimics the action of endogenous neurotrophic factors on brain protection and repair. In dementia models, Cerebrolysin decreases β-amyloid deposition and microtubule-associated protein tau phosphorylation by regulating glycogen synthase kinase-3β and cyclin-dependent kinase 5 activity, increases synaptic density and restores neuronal cytoarchitecture. These effects protect integrity of the neuronal circuits and thus result in improved cognitive and behavioral performance. Furthermore, Cerebrolysin enhances neurogenesis in the dentate gyrus, the basis for neuronal replacement therapy in neurodegenerative diseases. Experimental studies in stroke animal models have shown that Cerebrolysin stabilizes the structural integrity of cells by inhibition of calpain and reduces the number of apoptotic cells after ischemic lesion. Cerebrolysin induces restorative processes, decreases infarct volume and edema formation and promotes functional recovery. Stroke-induced neurogenesis in the subventricular zone was also promoted by Cerebrolysin, thus supporting the brain's self-repair after stroke. Both, traumatic brain and spinal cord injury conditions stimulate the expression of natural neurotrophic factors to promote repair and regeneration processes -axonal regeneration, neuronal plasticity and neurogenesis- that is considered to be crucial for the future recovery. Neuroprotective effects of Cerebrolysin on experimentally induced traumatic spinal cord injury have shown that Cerebrolysin prevents apoptosis of lesioned motoneurons and promotes functional recovery. This section summarizes the most relevant data on the pharmacology of Cerebrolysin obtained from in vitro assays (biochemical and cell cultures) and in vivo animal models of acute and chronic neurological disorders.

  18. Puerarin partly counteracts the inflammatory response after cerebral ischemia/reperfusion via activating the cholinergic anti-inflammatory pathway

    Institute of Scientific and Technical Information of China (English)

    Xiaojie Liu; Zhigang Mei; Jingping Qian; Yongbao Zeng; Mingzhi Wang

    2013-01-01

    Puerarin, a major isoflavonoid derived from the Chinese medical herb radix puerariae (Gegen), has been reported to inhibit neuronal apoptosis and play an anti-inflammatory role in focal cerebral ischemia model rats. Recent findings regarding stroke pathophysiology have recognized that an-ti-inflammation is an important target for the treatment of ischemic stroke. The cholinergic an-ti-inflammatory pathway is a highly robust neural-immune mechanism for inflammation control. This study was to investigate whether activating the cholinergic anti-inflammatory pathway can be in-volved in the mechanism of inhibiting the inflammatory response during puerarin-induced cerebral ischemia/reperfusion in rats. Results showed that puerarin pretreatment (intravenous injection) re-duced the ischemic infarct volume, improved neurological deficit after cerebral ischemia/reperfusion and decreased the levels of interleukin-1β, interleukin-6 and tumor necrosis factor-αin brain tissue. Pretreatment with puerarin (intravenous injection) attenuated the inflammatory response in rats, which was accompanied by janus-activated kinase 2 (JAK2) and signal transducers and activators of transcription 3 (STAT3) activation and nuclear factor kappa B (NF-κB) inhibition. These observa-tions were inhibited by the alpha7 nicotinic acetylcholine receptor (α7nAchR) antagonistα-bungarotoxin (α-BGT). In addition, puerarin pretreatment increased the expression of α7nAchR mRNA in ischemic cerebral tissue. These data demonstrate that puerarin pretreatment strongly protects the brain against cerebral ischemia/reperfusion injury and inhibits the inflammatory re-sponse. Our results also indicated that the anti-inflammatory effect of puerarin may partly be me-diated through the activation of the cholinergic anti-inflammatory pathway.

  19. High-dose hydroxocobalamin administered after H2S exposure counteracts sulfide-poisoning-induced cardiac depression in sheep.

    Science.gov (United States)

    Haouzi, Philippe; Chenuel, Bruno; Sonobe, Takashi

    2015-01-01

    Severe H2S poisoning leads to death by rapid respiratory and cardiac arrest, the latter can occur within seconds or minutes in severe forms of intoxication. To determine the time course and the nature of H2S-induced cardiac arrest and the effects of high-dose hydroxocobalamin administered after the end of sulfide exposure. NaHS was infused in 16 sedated mechanically ventilated sheep to reach concentrations of H2S in the blood, which was previously found to lead to cardiac arrest within minutes following the cessation of H2S exposure. High-dose hydroxocobalamin (5 g) or saline solution was administered intravenously, 1 min after the cessation of NaHS infusion. All animals were still alive at the cessation of H2S exposure. Three animals (18%) presented a cardiac arrest within 90 s and were unable to receive any antidote or vehicle. In the animals that survived long enough to receive either hydroxocobalamin or saline, 71% (5/7) died in the control group by cardiac arrest within 10 min. In all instances, cardiac arrest was the result of a pulseless electrical activity (PEA). In the group that received the antidote, intravenous injection of 5 g of hydroxocobalamin provoked an abrupt increase in blood pressure and blood flow; PEA was prevented in all instances. However, we could not find any evidence for a recovery in oxidative metabolism in the group receiving hydroxocobalamin, as blood lactate remained elevated and even continued to rise after 1 h, despite restored hemodynamics. This, along with an unaltered recovery of H2S kinetics, suggests that hydroxocobalamin did not act through a mechanism of H2S trapping. In this sheep model, there was a high risk for cardiac arrest, by PEA, persisting up to 10 min after H2S exposure. Very high dose of hydroxocobalamin (5 g), injected very early after the cessation of H2S exposure, improved cardiac contractility and prevented PEA.

  20. The benefits of staying active in old age: physical activity counteracts the negative influence of PICALM, BIN1, and CLU risk alleles on episodic memory functioning.

    Science.gov (United States)

    Ferencz, Beata; Laukka, Erika J; Welmer, Anna-Karin; Kalpouzos, Grégoria; Angleman, Sara; Keller, Lina; Graff, Caroline; Lövdén, Martin; Bäckman, Lars

    2014-06-01

    PICALM, BIN1, CLU, and APOE are top candidate genes for Alzheimer's disease, and they influence episodic memory performance in old age. Physical activity, however, has been shown to protect against age-related decline and counteract genetic influences on cognition. The aims of this study were to assess whether (a) a genetic risk constellation of PICALM, BIN1, and CLU polymorphisms influences cognitive performance in old age; and (b) if physical activity moderates this effect. Data from the SNAC-K population-based study were used, including 2,480 individuals (age range = 60 to 100 years) free of dementia at baseline and at 3- to 6-year follow-ups. Tasks assessing episodic memory, perceptual speed, knowledge, and verbal fluency were administered. Physical activity was measured using self-reports. Individuals who had engaged in frequent health- or fitness-enhancing activities within the past year were compared with those who were inactive. Genetic risk scores were computed based on an integration of risk alleles for PICALM (rs3851179 G allele, rs541458 T allele), BIN1 (rs744373 G allele), and CLU (rs11136000 T allele). High genetic risk was associated with reduced episodic memory performance, controlling for age, education, vascular risk factors, chronic diseases, activities of daily living, and APOE gene status. Critically, physical activity attenuated the effects of genetic risk on episodic memory. Our findings suggest that participants with high genetic risk who maintain a physically active lifestyle show selective benefits in episodic memory performance.

  1. An observational, prospective, two-cohort comparison of a fixed versus variable dosing strategy of prothrombin complex concentrate to counteract vitamin K antagonists in 240 bleeding emergencies.

    Science.gov (United States)

    Khorsand, Nakisa; Veeger, Nic J G M; van Hest, Reinier M; Ypma, Paula F; Heidt, Jeroen; Meijer, Karina

    2012-10-01

    Despite years of experience with vitamin K antagonist-associated bleeding events, there is still no evidence to help identify the optimal treatment with prothrombin complex concentrates. Variable dosing and fixed dose strategies are being used. In this observational prospective two-cohort study, we aimed to assess the non-inferiority of a low fixed PCC dose (1,040 IU Factor IX) compared to the registered variable dosing regimen based on baseline International Normalized Rate, bodyweight, and target International Normalized Rate, to counteract vitamin K antagonists in a bleeding emergency in a daily clinical practice setting. Non-inferiority of the fixed prothrombin complex concentrate dose was hypothesized with a margin of 4%. Main end points were proportion of patients reaching the target International Normalized Rate (complex concentrate treatment, and successful clinical outcome. Target International Normalized Rate was reached in 92% of the fixed dose patients (n=101) versus 95% of variable dose patients (n=139) resulting in a risk difference of -2.99% (90% CI: - 8.6 to 2.7) (non-inferiority not confirmed). Clinical outcome was successful in 96% and 88% of fixed versus variable dose, respectively, with a risk difference of 8.3% (90% CI: 2.7-13.9; non-inferiority confirmed). Although a lower fixed prothrombin complex concentrate dose was associated with successful clinical outcome, fewer patients reached the target International Normalized Rate.

  2. A comparison of the potency of newly developed oximes (K027, K048) and commonly used oximes (obidoxime, HI-6) to counteract tabun-induced neurotoxicity in rats.

    Science.gov (United States)

    Kassa, Jirí; Kunesova, Gabriela

    2006-01-01

    The neuroprotective effects of newly developed oximes (K027, K048) and currently available oximes (obidoxime, HI-6) in combination with atropine in rats poisoned with tabun at a sublethal dose (170 microg kg(-1) i.m.; 80% of LD(50) value) were studied. The tabun-induced neurotoxicity was monitored using a functional observational battery and an automatic measurement of motor activity. The neurotoxicity of tabun was monitored at 24 h and 7 days following tabun challenge. The results indicate that the oxime HI-6 in combination with atropine was not able to protect the rats from the lethal effects of tabun. Two non-treated tabun-poisoned rats and one tabun-poisoned rat treated with atropine combined with HI-6 died within 2 h. On the other hand, all other tested oximes combined with atropine allowed all the tabun-poisoned rats to survive 7 days following tabun challenge. Both newly developed oximes combined with atropine seem to be sufficiently effective antidotes for a decrease in tabun-induced neurotoxicity in the case of sublethal poisoning although they are not able to eliminate tabun-induced neurotoxicity completely. The neuroprotective efficacy of obidoxime in combination with atropine approached the potency of newly developed oximes but the ability of the oxime HI-6 to counteract tabun-induced acute neurotoxicity was significantly lower, especially at 24 h after tabun poisoning. Due to their neuroprotective effects, both newly developed oximes appear to be suitable oximes for the antidotal treatment of acute tabun poisoning.

  3. M3-receptor activation counteracts opioid-mediated apneusis, but the apneusis per se is not necessarily related to an impaired M3 mechanism in rats.

    Science.gov (United States)

    Niwa, Yuka; Haji, Akira

    2011-11-07

    Morphine slows the respiratory cycle due to a predominant prolongation of inspiration (apneusis) by postponing the spontaneous termination of inspiration (inspiratory off-switching). The present study investigates whether the morphine-induced apneusis results from impairment of cholinergic mechanisms in the central respiratory network. The efferent discharge was recorded from the phrenic nerve in artificially ventilated and anesthetized rats with vagotomy. All drugs were injected intravenously. The phrenic nerve displayed an augmenting discharge during inspiration and arrest of discharge during expiration in normal condition. Administration of morphine (0.3-10.0mg/kg) dose-dependently provoked apneusis characterized by a long-lasting, plateau inspiratory discharge of the phrenic nerve. It shortened the expiratory duration. Subsequent administration of physostigmine (0.1mg/kg) restored the morphine-induced apneusis to eupnea with a partial recovery of the augmenting inspiratory discharge. This modification of physostigmine was blocked by a non-specific muscarinic antagonist scopolamine (3.0mg/kg), leading to re-prolongation of inspiration. A similar antagonism was affected by an antagonist of M3 cholinergic receptors, 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, 1.0 and 10.0mg/kg) but not by an antagonist of M1 cholinergic receptors, pirenzepine (1.0 and 10.0mg/kg). These results demonstrate that the activation of endogenous M3 cholinergic mechanisms counteracts the morphine-induced apneusis. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Organization into Higher Ordered Ring Structures Counteracts Membrane Binding of IM30, a Protein Associated with Inner Membranes in Chloroplasts and Cyanobacteria.

    Science.gov (United States)

    Heidrich, Jennifer; Wulf, Verena; Hennig, Raoul; Saur, Michael; Markl, Jürgen; Sönnichsen, Carsten; Schneider, Dirk

    2016-07-15

    The IM30 (inner membrane-associated protein of 30 kDa), also known as the Vipp1 (vesicle-inducing protein in plastids 1), has a crucial role in thylakoid membrane biogenesis and maintenance. Recent results suggest that the protein binds peripherally to membranes containing negatively charged lipids. However, although IM30 monomers interact and assemble into large oligomeric ring complexes with different numbers of monomers, it is still an open question whether ring formation is crucial for membrane interaction. Here we show that binding of IM30 rings to negatively charged phosphatidylglycerol membrane surfaces results in a higher ordered membrane state, both in the head group and in the inner core region of the lipid bilayer. Furthermore, by using gold nanorods covered with phosphatidylglycerol layers and single particle spectroscopy, we show that not only IM30 rings but also lower oligomeric IM30 structures interact with membranes, although with higher affinity. Thus, ring formation is not crucial for, and even counteracts, membrane interaction of IM30.

  5. Ghrelin-induced orexigenic effect in rats depends on the metabolic status and is counteracted by peripheral CB1 receptor antagonism.

    Directory of Open Access Journals (Sweden)

    Francisco Alen

    Full Text Available Ghrelin is an endogenous regulator of energy homeostasis synthesized by the stomach to stimulate appetite and positive energy balance. Similarly, the endocannabinoid system is part of our internal machinery controlling food intake and energy expenditure. Both peripheral and central mechanisms regulate CB1-mediated control of food intake and a functional relationship between hypothalamic ghrelin and cannabinoid CB1 receptor has been proposed. First of all, we investigated brain ghrelin actions on food intake in rats with different metabolic status (negative or equilibrate energy balance. Secondly, we tested a sub-anxiogenic ultra-low dose of the CB1 antagonist SR141716A (Rimonabant and the peripheral-acting CB1 antagonist LH-21 on ghrelin orexigenic actions. We found that: 1 central administration of ghrelin promotes food intake in free feeding animals but not in 24 h food-deprived or chronically food-restricted animals; 2 an ultra-low dose of SR141716A (a subthreshold dose 75 folds lower than the EC50 for induction of anxiety completely counteracts the orexigenic actions of central ghrelin in free feeding animals; 3 the peripheral-restricted CB1 antagonist LH-21 blocks ghrelin-induced hyperphagia in free feeding animals. Our study highlights the importance of the animaĺs metabolic status for the effectiveness of ghrelin in promoting feeding, and suggests that the peripheral endocannabinoid system may interact with ghrelińs signal in the control of food intake under equilibrate energy balance conditions.

  6. 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

    Directory of Open Access Journals (Sweden)

    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.

  7. Inability of HDL from type 2 diabetic patients to counteract the inhibitory effect of oxidised LDL on endothelium-dependent vasorelaxation.

    Science.gov (United States)

    Perségol, L; Vergès, B; Foissac, M; Gambert, P; Duvillard, L

    2006-06-01

    In healthy normolipidaemic and normoglycaemic control subjects, HDL are able to reverse the inhibition of vasodilation that is induced by oxidised LDL. In type 2 diabetic patients, HDL are glycated and more triglyceride-rich than in control subjects. These alterations are likely to modify the capacity of HDL to reverse the inhibition of vasodilation induced by oxidised LDL. Using rabbit aorta rings, we compared the ability of HDL from 16 type 2 diabetic patients and 13 control subjects to suppress the inhibition of vasodilation that is induced by oxidised LDL. Oxidised LDL inhibited endothelium-dependent vasodilation (maximal relaxation [Emax] = 58.2+/-14.6 vs 99.3+/-5.2% for incubation without any lipoprotein, p HDL from control subjects significantly reduced the inhibitory effect of oxidised LDL on vasodilatation (Emax = 77.6+/-12.9 vs 59.5+/-7.7%, p HDL from type 2 diabetic patients had no effect (Emax = 52.4+/-20.4 vs 57.2+/-18.7%, NS). HDL triglyceride content was significantly higher in type 2 diabetic patients than in control subjects (5.3+/-2.2 vs 3.1+/-1.4%, p HDL in type 2 diabetic patients (r = -0.71, p diabetes mellitus, the ability of HDL to counteract the inhibition of endothelium-dependent vasorelaxation induced by oxidised LDL is impaired and is inversely correlated with HDL triglyceride content. These findings suggest that HDL are less atheroprotective in type 2 diabetic patients than in control subjects.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Ghrelin-Induced Orexigenic Effect in Rats Depends on the Metabolic Status and Is Counteracted by Peripheral CB1 Receptor Antagonism

    Science.gov (United States)

    Alen, Francisco; Crespo, Inmaculada; Ramírez-López, María Teresa; Jagerovic, Nadine; Goya, Pilar; de Fonseca, Fernando Rodríguez; de Heras, Raquel Gómez; Orio, Laura

    2013-01-01

    Ghrelin is an endogenous regulator of energy homeostasis synthesized by the stomach to stimulate appetite and positive energy balance. Similarly, the endocannabinoid system is part of our internal machinery controlling food intake and energy expenditure. Both peripheral and central mechanisms regulate CB1-mediated control of food intake and a functional relationship between hypothalamic ghrelin and cannabinoid CB1 receptor has been proposed. First of all, we investigated brain ghrelin actions on food intake in rats with different metabolic status (negative or equilibrate energy balance). Secondly, we tested a sub-anxiogenic ultra-low dose of the CB1 antagonist SR141716A (Rimonabant) and the peripheral-acting CB1 antagonist LH-21 on ghrelin orexigenic actions. We found that: 1) central administration of ghrelin promotes food intake in free feeding animals but not in 24 h food-deprived or chronically food-restricted animals; 2) an ultra-low dose of SR141716A (a subthreshold dose 75 folds lower than the EC50 for induction of anxiety) completely counteracts the orexigenic actions of central ghrelin in free feeding animals; 3) the peripheral-restricted CB1 antagonist LH-21 blocks ghrelin-induced hyperphagia in free feeding animals. Our study highlights the importance of the animaĺs metabolic status for the effectiveness of ghrelin in promoting feeding, and suggests that the peripheral endocannabinoid system may interact with ghrelińs signal in the control of food intake under equilibrate energy balance conditions. PMID:23565287

  10. Solar irradiance reduction to counteract radiative forcing from a quadrupling of CO2: climate responses simulated by four earth system models

    Directory of Open Access Journals (Sweden)

    M. Lawrence

    2012-06-01

    Full Text Available In this study we compare the response of four state-of-the-art Earth system models to climate engineering under scenario G1 of two model intercomparison projects: GeoMIP (Geoengineering Model Intercomparison Project and IMPLICC (EU project "Implications and risks of engineering solar radiation to limit climate change". In G1, the radiative forcing from an instantaneous quadrupling of the CO2 concentration, starting from the preindustrial level, is balanced by a reduction of the solar constant. Model responses to the two counteracting forcings in G1 are compared to the preindustrial climate in terms of global means and regional patterns and their robustness. While the global mean surface air temperature in G1 remains almost unchanged compared to the control simulation, the meridional temperature gradient is reduced in all models. Another robust response is the global reduction of precipitation with strong effects in particular over North and South America and northern Eurasia. In comparison to the climate response to a quadrupling of CO2 alone, the temperature responses are small in experiment G1. Precipitation responses are, however, in many regions of comparable magnitude but globally of opposite sign.

  11. Brain catechol-O-methyltransferase (COMT) inhibition by tolcapone counteracts recognition memory deficits in normal and chronic phencyclidine-treated rats and in COMT-Val transgenic mice.

    Science.gov (United States)

    Detrait, Eric R; Carr, Greg V; Weinberger, Daniel R; Lamberty, Yves

    2016-08-01

    The critical involvement of dopamine in cognitive processes has been well established, suggesting that therapies targeting dopamine metabolism may alleviate cognitive dysfunction. Catechol-O-methyl transferase (COMT) is a catecholamine-degrading enzyme, the substrates of which include dopamine, epinephrine, and norepinephrine. The present work illustrates the potential therapeutic efficacy of COMT inhibition in alleviating cognitive impairment. A brain-penetrant COMT inhibitor, tolcapone, was tested in normal and phencyclidine-treated rats and COMT-Val transgenic mice. In a novel object recognition procedure, tolcapone counteracted a 24-h-dependent forgetting of a familiar object as well as phencyclidine-induced recognition deficits in the rats at doses ranging from 7.5 to 30 mg/kg. In contrast, entacapone, a COMT inhibitor that does not readily cross the blood-brain barrier, failed to show efficacy at doses up to 30 mg/kg. Tolcapone at a dose of 30 mg/kg also improved novel object recognition performance in transgenic mice, which showed clear recognition deficits. Complementing earlier studies, our results indicate that central inhibition of COMT positively impacts recognition memory processes and might constitute an appealing treatment for cognitive dysfunction related to neuropsychiatric disorders.

  12. Single-Word Recognition Need Not Depend on Single-Word Features: Narrative Coherence Counteracts Effects of Single-Word Features that Lexical Decision Emphasizes.

    Science.gov (United States)

    Teng, Dan W; Wallot, Sebastian; Kelty-Stephen, Damian G

    2016-12-01

    Research on reading comprehension of connected text emphasizes reliance on single-word features that organize a stable, mental lexicon of words and that speed or slow the recognition of each new word. However, the time needed to recognize a word might not actually be as fixed as previous research indicates, and the stability of the mental lexicon may change with task demands. The present study explores the effects of narrative coherence in self-paced story reading to single-word feature effects in lexical decision. We presented single strings of letters to 24 participants, in both lexical decision and self-paced story reading. Both tasks included the same words composing a set of adjective-noun pairs. Reading times revealed that the tasks, and the order of the presentation of the tasks, changed and/or eliminated familiar effects of single-word features. Specifically, experiencing the lexical-decision task first gradually emphasized the role of single-word features, and experiencing the self-paced story-reading task afterwards counteracted the effect of single-word features. We discuss the implications that task-dependence and narrative coherence might have for the organization of the mental lexicon. Future work will need to consider what architectures suit the apparent flexibility with which task can accentuate or diminish effects of single-word features.

  13. Neonatal monosodium glutamate treatment counteracts circadian arrhythmicity induced by phase shifts of the light-dark cycle in female and male Siberian hamsters.

    Science.gov (United States)

    Prendergast, Brian J; Onishi, Kenneth G; Zucker, Irving

    2013-07-12

    Studies of rats and voles suggest that distinct pathways emanating from the anterior hypothalamic-retrochiasmatic area and the mediobasal hypothalamic arcuate nucleus independently generate ultradian rhythms (URs) in hormone secretion and behavior. We evaluated the hypothesis that destruction of arcuate nucleus (ARC) neurons, in concert with dampening of suprachiasmatic nucleus (SCN) circadian rhythmicity, would compromize the generation of ultradian rhythms (URs) of locomotor activity. Siberian hamsters retain-->of both sexes treated neonatally with monosodium glutamate (MSG) that destroys ARC neurons were subjected in adulthood to a circadian disrupting phase-shift protocol (DPS) that produces SCN arrhythmia. MSG treatments induced hypogonadism and obesity, retain-->and markedly reduced the size of the optic chiasm and optic nerves. MSG-treated hamsters exhibited normal entrainment to the light-dark cycle, but MSG treatretain-->ment counteracted the circadian arrhythmicity induced by the DPS protocol: only 6% of retain-->MSG-treated hamsters exhibited circadian arrhythmia, whereas 50% of control hamsters were circadian disrupted. In MSG-treated hamsters that retained circadian rhythmicity after DPS treatment, quantitative parameters of URs appeared normal, but in the two MSG-treated hamsters that became circadian arrhythmic after DPS, both dark-phase and light-phase URs were abolished. Although preliminary, these data are consistent with reports in voles suggesting that the combined disruption of SCN and ARC function impairs the expression of behavioral URs. The data also suggest that light thresholds for entrainment of circadian rhythms may be lower than those required to disrupt circadian organization.

  14. EARTHQUAKES - VOLCANOES (Causes - Forecast - Counteraction)

    Science.gov (United States)

    Tsiapas, Elias

    2014-05-01

    Earthquakes and volcanoes are caused by: 1)Various liquid elements (e.g. H20, H2S, S02) which emerge from the pyrosphere and are trapped in the space between the solid crust and the pyrosphere (Moho discontinuity). 2)Protrusions of the solid crust at the Moho discontinuity (mountain range roots, sinking of the lithosphere's plates). 3)The differential movement of crust and pyrosphere. The crust misses one full rotation for approximately every 100 pyrosphere rotations, mostly because of the lunar pull. The above mentioned elements can be found in small quantities all over the Moho discontinuity, and they are constantly causing minor earthquakes and small volcanic eruptions. When large quantities of these elements (H20, H2S, SO2, etc) concentrate, they are carried away by the pyrosphere, moving from west to east under the crust. When this movement takes place under flat surfaces of the solid crust, it does not cause earthquakes. But when these elements come along a protrusion (a mountain root) they concentrate on its western side, displacing the pyrosphere until they fill the space created. Due to the differential movement of pyrosphere and solid crust, a vacuum is created on the eastern side of these protrusions and when the aforementioned liquids overfill this space, they explode, escaping to the east. At the point of their escape, these liquids are vaporized and compressed, their flow accelerates, their temperature rises due to fluid friction and they are ionized. On the Earth's surface, a powerful rumbling sound and electrical discharges in the atmosphere, caused by the movement of the gasses, are noticeable. When these elements escape, the space on the west side of the protrusion is violently taken up by the pyrosphere, which collides with the protrusion, causing a major earthquake, attenuation of the protrusions, cracks on the solid crust and damages to structures on the Earth's surface. It is easy to foresee when an earthquake will occur and how big it is going to be, when we know the record of specific earthquakes and the routes they have followed towards the East. For example, to foresee an earthquake in the Mediterranean region, we take starting point earthquakes to Latin America (0°-40°).The aforementioned elements will reach Italy in an average time period of 49 days and Greece in 53 days. The most reliable preceding phenomenon to determine the epicenter of an earthquake is the rise of the crust's temperature at the area where a large quantity of elements is concentrated, among other phenomena that can be detected either by instruments or by our senses. When there is an active volcano along the route between the area where the "starting-point" earthquake occurred and the area where we expect the same elements to cause a new earthquake, it is possible these elements will escape through the volcano's crater, carrying lava with them. We could contribute to that end, nullifying earthquakes that might be triggered by these elements further to the east, by using manmade resources, like adequate quantities of explosives at the right moment.

  15. 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

  16. Population genetic structure in Myrtus communis L. in a chronically fragmented landscape in the Mediterranean: can gene flow counteract habitat perturbation?

    Science.gov (United States)

    Albaladejo, R G; Carrillo, L F; Aparicio, A; Fernández-Manjarrés, J F; González-Varo, J P

    2009-05-01

    Ancient managed landscapes provide ideal opportunities to assess the consequences of habitat fragmentation on the patterns of genetic diversity and gene flow in long-lived plant species. Using amplified fragment length polymorphism (AFLP) and allozyme markers, we quantified seed-mediated gene flow and population genetic diversity and structure in 14 populations of Myrtus communis (myrtle), a common endozoochorous shrub species of forest patches in lowland agricultural Mediterranean areas. Overall, allozyme diversity for myrtle was low (P(95) = 25%; A = 1.411; H(e) = 0.085) compared to other known populations, and a significant portion of populations (57%) had lower levels of allelic diversity and/or heterozygosity than expected at random, as shown by simulated resampling of the whole diversity of the landscape. We found significant correlations between allozyme variability and population size and patch isolation, but no significant inbreeding in any population. Genetic differentiation among populations for both allozyme and AFLP markers was significant (Phi(ST) = 0.144 and Phi(ST) = 0.142, respectively) but an isolation-by-distance pattern was not detected. Assignment tests on AFLP data indicated a high immigration rate in the populations (ca. 20-22%), likely through effective seed dispersal across the landscape by birds and mammals. Our results suggest that genetic isolation is not the automatic outcome of habitat destruction since substantial levels of seed-mediated gene flow are currently detectable. However, even moderate rates of gene flow seem insufficient in this long-lived species to counteract the genetic erosion and differentiation imposed by chronic habitat destruction.

  17. A comparison of the potency of newly developed oximes (K074, K075) and commonly used oximes (obidoxime, HI-6) to counteract tabun-induced neurotoxicity in rats.

    Science.gov (United States)

    Kassa, Jiri; Karasova, Jana

    2007-01-05

    The neuroprotective effects of newly developed oximes (K074, K075) and currently available oximes (obidoxime, HI-6) in combination with atropine in rats poisoned with tabun at a sublethal dose (180 micro g/kg i.m.; 80% LD(50)) were studied. The tabun-induced neurotoxicity was monitored using a functional observational battery and an automatic measurement of motor activity. The neurotoxicity of tabun was monitored at 24h and 7 days following tabun challenge. The results indicate that all oximes studied in combination with atropine allow all tabun-poisoned rats to survive within 7 days following tabun challenge while two non-treated tabun-poisoned rats died within 2h. Both newly developed oximes combined with atropine seem to be effective antidotes for a decrease in tabun-induced neurotoxicity in the case of sublethal poisoning although they are not able to eliminate tabun-induced neurotoxicity completely. The oxime K075 showed a higher neuroprotective efficacy against tabun than K074 according to the number of eliminated tabun-induced neurotoxic signs at 24h as well as 7 days after tabun challenge. The neuroprotective efficacy of obidoxime in combination with atropine is similar to the potency of newly developed oxime K075 but the ability of the oxime HI-6 to counteract tabun-induced acute neurotoxicity is significantly lower at 24h as well as 7 days after tabun poisoning. Due to their neuroprotective effects, both newly developed oximes (especially K075) appear to be more suitable oximes for the antidotal treatment of acute tabun poisonings than the oxime HI-6.

  18. Targeting of Proteoglycan Synthesis Pathway: A New Strategy to Counteract Excessive Matrix Proteoglycan Deposition and Transforming Growth Factor-β1-Induced Fibrotic Phenotype in Lung Fibroblasts.

    Science.gov (United States)

    Shaukat, Irfan; Barré, Lydia; Venkatesan, Narayanan; Li, Dong; Jaquinet, Jean-Claude; Fournel-Gigleux, Sylvie; Ouzzine, Mohamed

    2016-01-01

    Stimulation of proteoglycan (PG) synthesis and deposition plays an important role in the pathophysiology of fibrosis and is an early and dominant feature of pulmonary fibrosis. Transforming growth factor-β1 (TGF-β1) is a major cytokine associated with fibrosis that induces excessive synthesis of matrix proteins, particularly PGs. Owing to the importance of PGs in matrix assembly and in mediating cytokine and growth factor signaling, a strategy based on the inhibition of PG synthesis may prevent excessive matrix PG deposition and attenuates profibrotic effects of TGF-β1 in lung fibroblasts. Here, we showed that 4-MU4-deoxy-β-D-xylopyranoside, a competitive inhibitor of β4-galactosyltransferase7, inhibited PG synthesis and secretion in a dose-dependent manner by decreasing the level of both chondroitin/dermatan- and heparin-sulfate PG in primary lung fibroblasts. Importantly, 4-MU4-deoxy-xyloside was able to counteract TGF-β1-induced synthesis of PGs, activation of fibroblast proliferation and fibroblast-myofibroblast differentiation. Mechanistically, 4-MU4-deoxy-xyloside treatment inhibited TGF-β1-induced activation of canonical Smads2/3 signaling pathway in lung primary fibroblasts. The knockdown of β4-galactosyltransferase7 mimicked 4-MU4-deoxy-xyloside effects, indicating selective inhibition of β4-galactosyltransferase7 by this compound. Collectively, this study reveals the anti-fibrotic activity of 4-MU4-deoxy-xyloside and indicates that inhibition of PG synthesis represents a novel strategy for the treatment of lung fibrosis.

  19. Counteracting negative venous line pressures to avoid arterial air bubbles: an experimental study comparing two different types of miniaturized extracorporeal perfusion systems.

    Science.gov (United States)

    Aboud, Anas; Mederos-Dahms, Hendrikje; Liebing, Kai; Zittermann, Armin; Schubert, Harald; Murray, Edward; Renner, Andre; Gummert, Jan; Börgermann, Jochen

    2015-05-29

    Because of its low rate of clinical complications, miniaturized extracorporeal perfusion systems (MEPS) are frequently used in heart centers worldwide. However, many recent studies refer to the higher probability of gaseous microemboli formation by MEPS, caused by subzero pressure values. This is the main reason why various de-airing devices were developed for today's perfusion systems. In the present study, we investigated the potential benefits of a simple one-way-valve connected to a volume replacement reservoir (OVR) for volume and pressure compensation. In an experimental study on 26 pigs, we compared MEPS (n = 13) with MEPS plus OVR (n = 13). Except OVR, perfusion equipment was identical in both groups. Primary endpoints were pressure values in the venous line and the right atrium as well as the number and volume of air bubbles. Secondary endpoints were biochemical parameters of systemic inflammatory response, ischemia, hemodilution and hemolysis. One animal was lost in the MEPS + OVR group. In the MEPS + OVR group no pressure values below -150 mmHg in the venous line and no values under -100 mmHg in right atrium were noticed. On the contrary, nearly 20% of venous pressure values in the MEPS group were below -150 and approximately 10% of right atrial pressure values were below -100 mmHg. Compared with the MEPS group, the bubble counter device showed lower numbers of arterial air bubbles in the MEPS + OVR group (mean ± SD: 13444 ± 5709 vs. 1 ± 2, respectively; p system with a volume replacement reservoir is able to counteract excessive negative venous line pressures and to reduce the number and volume of arterial air bubbles. This approach may lead to a lower rate of neurological complications.

  20. Histamine H3 receptor activation counteracts adenosine A2A receptor-mediated enhancement of depolarization-evoked [3H]-GABA release from rat globus pallidus synaptosomes.

    Science.gov (United States)

    Morales-Figueroa, Guadalupe-Elide; Márquez-Gómez, Ricardo; González-Pantoja, Raúl; Escamilla-Sánchez, Juan; Arias-Montaño, José-Antonio

    2014-08-20

    High levels of histamine H3 receptors (H3Rs) are found in the globus pallidus (GP), a neuronal nucleus in the basal ganglia involved in the control of motor behavior. By using rat GP isolated nerve terminals (synaptosomes), we studied whether H3R activation modified the previously reported enhancing action of adenosine A2A receptor (A2AR) stimulation on depolarization-evoked [(3)H]-GABA release. At 3 and 10 nM, the A2AR agonist CGS-21680 enhanced [(3)H]-GABA release induced by high K(+) (20 mM) and the effect of 3 nM CGS-21680 was prevented by the A2AR antagonist ZM-241385 (100 nM). The presence of presynaptic H3Rs was confirmed by the specific binding of N-α-[methyl-(3)H]-histamine to membranes from GP synaptosomes (maximum binding, Bmax, 1327 ± 79 fmol/mg protein; dissociation constant, Kd, 0.74 nM), which was inhibited by the H3R ligands immepip, clobenpropit, and A-331440 (inhibition constants, Ki, 0.28, 8.53, and 316 nM, respectively). Perfusion of synaptosomes with the H3R agonist immepip (100 nM) had no effect on K(+)-evoked [(3)H]-GABA release, but inhibited the stimulatory action of A2AR activation. In turn, the effect of immepip was blocked by the H3R antagonist clobenpropit, which had no significant effect of its own on K(+)-induced [(3)H]-GABA release. These data indicate that H3R activation selectively counteracts the facilitatory action of A2AR stimulation on GABA release from striato-pallidal projections.

  1. Cellular responses of Candida albicans to phagocytosis and the extracellular activities of neutrophils are critical to counteract carbohydrate starvation, oxidative and nitrosative stress.

    Science.gov (United States)

    Miramón, Pedro; Dunker, Christine; Windecker, Hanna; Bohovych, Iryna M; Brown, Alistair J P; Kurzai, Oliver; Hube, Bernhard

    2012-01-01

    Neutrophils are key players during Candida albicans infection. However, the relative contributions of neutrophil activities to fungal clearance and the relative importance of the fungal responses that counteract these activities remain unclear. We studied the contributions of the intra- and extracellular antifungal activities of human neutrophils using diagnostic Green Fluorescent Protein (GFP)-marked C. albicans strains. We found that a carbohydrate starvation response, as indicated by up-regulation of glyoxylate cycle genes, was only induced upon phagocytosis of the fungus. Similarly, the nitrosative stress response was only observed in internalised fungal cells. In contrast, the response to oxidative stress was observed in both phagocytosed and non-phagocytosed fungal cells, indicating that oxidative stress is imposed both intra- and extracellularly. We assessed the contributions of carbohydrate starvation, oxidative and nitrosative stress as antifungal activities by analysing the resistance to neutrophil killing of C. albicans mutants lacking key glyoxylate cycle, oxidative and nitrosative stress genes. We found that the glyoxylate cycle plays a crucial role in fungal resistance against neutrophils. The inability to respond to oxidative stress (in cells lacking superoxide dismutase 5 or glutathione reductase 2) renders C. albicans susceptible to neutrophil killing, due to the accumulation of reactive oxygen species (ROS). We also show that neutrophil-derived nitric oxide is crucial for the killing of C. albicans: a yhb1Δ/Δ mutant, unable to detoxify NO•, was more susceptible to neutrophils, and this phenotype was rescued by the nitric oxide scavenger carboxy-PTIO. The stress responses of C. albicans to neutrophils are partially regulated via the stress regulator Hog1 since a hog1Δ/Δ mutant was clearly less resistant to neutrophils and unable to respond properly to neutrophil-derived attack. Our data indicate that an appropriate fungal response to all

  2. Aquaphilus dolomiae extract counteracts the effects of cutaneous S. aureus secretome isolated from atopic children on CD4(+) T cell activation.

    Science.gov (United States)

    Martin, Hélène; Laborel-Préneron, Emeline; Fraysse, Frédérique; Nguyen, Thien; Schmitt, Anne-Marie; Redoulès, Daniel; Davrinche, Christian

    2016-11-01

    Skin microbiota takes part in the control of cutaneous inflammation. In skin diseases such as atopic dermatitis (AD) cutaneous dysbiosis and the emergence of Staphylococcus aureus contribute to the pathophysiology of the disease. New therapeutic approaches consist in topical application of natural products able to counteract S. aureus effects through activation of resident immune cells producing anti-inflammatory cytokines such as IL-10. This study investigates the potential immunosuppressive properties of Aquaphilus dolomiae (Neisseriaceae), a flagellated bacterium contained in Avène Thermal Spring Water used in hydrotherapy treatments of AD patients. An aqueous protein extract of Aquaphilus dolomiae (ADE, 60 μg/mL) was added to human monocyte-derived dendritic cells (moDC) for 24 h. Expression of HLA-DR, CD86 and CD83 was evaluated by flow cytometry and released cytokines (IL-10, IL-12) by cytometry bead array assay. The proliferation of allogeneic CFSE-labelled CD4(+ )T cells stimulated with ADE-conditioned moDC and S. aureus secretome was analysed by flow cytometry. MoDC exposed to ADE expressed lower levels of HLA-DR and CD86 than untreated cells, no CD83 and secreted barely detectable IL-12 but high amounts of IL-10 (N = 12, p S. aureus secretome on CD4(+ )T cells was reduced (p S. aureus secretome on CD4(+)T cells. Owing to the role of S. aureus colonization in driving inflammation in AD the immunosuppressive property of the ADE might be useful to reduce disease severity.

  3. 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.

  4. Targeting of Proteoglycan Synthesis Pathway: A New Strategy to Counteract Excessive Matrix Proteoglycan Deposition and Transforming Growth Factor-β1-Induced Fibrotic Phenotype in Lung Fibroblasts

    Science.gov (United States)

    Shaukat, Irfan; Barré, Lydia; Venkatesan, Narayanan; Li, Dong; Jaquinet, Jean-Claude; Fournel-Gigleux, Sylvie; Ouzzine, Mohamed

    2016-01-01

    Stimulation of proteoglycan (PG) synthesis and deposition plays an important role in the pathophysiology of fibrosis and is an early and dominant feature of pulmonary fibrosis. Transforming growth factor-β1 (TGF-β1) is a major cytokine associated with fibrosis that induces excessive synthesis of matrix proteins, particularly PGs. Owing to the importance of PGs in matrix assembly and in mediating cytokine and growth factor signaling, a strategy based on the inhibition of PG synthesis may prevent excessive matrix PG deposition and attenuates profibrotic effects of TGF-β1 in lung fibroblasts. Here, we showed that 4-MU4-deoxy-β-D-xylopyranoside, a competitive inhibitor of β4-galactosyltransferase7, inhibited PG synthesis and secretion in a dose-dependent manner by decreasing the level of both chondroitin/dermatan- and heparin-sulfate PG in primary lung fibroblasts. Importantly, 4-MU4-deoxy-xyloside was able to counteract TGF-β1-induced synthesis of PGs, activation of fibroblast proliferation and fibroblast-myofibroblast differentiation. Mechanistically, 4-MU4-deoxy-xyloside treatment inhibited TGF-β1-induced activation of canonical Smads2/3 signaling pathway in lung primary fibroblasts. The knockdown of β4-galactosyltransferase7 mimicked 4-MU4-deoxy-xyloside effects, indicating selective inhibition of β4-galactosyltransferase7 by this compound. Collectively, this study reveals the anti-fibrotic activity of 4-MU4-deoxy-xyloside and indicates that inhibition of PG synthesis represents a novel strategy for the treatment of lung fibrosis. PMID:26751072

  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. The Angiotensin-(1-7)/Mas Axis Counteracts Angiotensin II-Dependent and -Independent Pro-inflammatory Signaling in Human Vascular Smooth Muscle Cells.

    Science.gov (United States)

    Villalobos, Laura A; San Hipólito-Luengo, Álvaro; Ramos-González, Mariella; Cercas, Elena; Vallejo, Susana; Romero, Alejandra; Romacho, Tania; Carraro, Raffaele; Sánchez-Ferrer, Carlos F; Peiró, Concepción

    2016-01-01

    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)-1β. Methods and Results: In cultured HASMC, the expression of inducible nitric oxide synthase (iNOS) and the release of nitric oxide were stimulated by both Ang II and IL-1β, 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-Pro(7)-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 nuclear factor (NF)-κB. Indeed, Ang-(1-7) markedly inhibited the activation of the NADPH oxidase and subsequently of NF-κB, as determined by lucigenin-derived chemiluminescence 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.

  7. A comparison of the potency of newly developed oximes (K074, K075) and currently available oximes (obidoxime, trimedoxime, HI-6) to counteract acute toxic effects of tabun and cyclosarin in mice.

    Science.gov (United States)

    Kassa, Jirí; Humlicek, Vojtech

    2008-01-01

    The potency of newly developed oximes (K074, K075) and commonly used oximes (obidoxime, trimedoxime, and HI-6) to counteract tabun or cyclosarin-induced acute toxic effects was studied in mice. The therapeutic efficacy of trimedoxime and both newly developed oximes (K074, K075) was significantly higher than the potency of obidoxime and the oxime HI-6 in the case of acute tabun poisonings. On the other hand, the oxime HI-6 was significantly more efficacious than other studied oximes when mice were intoxicated with cyclosarin. The findings support the hypothesis that the therapeutic efficacy of oximes depends on the type of nerve agent. Due to their therapeutic efficacy, both newly developed K oximes can be considered to be promising oximes for the antidotal treatment of acute tabun poisonings, while the oxime HI-6 is still the most promising oxime for the treatment of acute cyclosarin poisonings due to its high potency to counteract cyclosarin-induced acute toxic effects.

  8. Arleigh Burke Destroyers: Delaying Procurement of DDG 51 Flight III Ships Would Allow Time to Increase Design Knowledge

    Science.gov (United States)

    2015-08-01

    MAMDJF Maritime and Missile Defense of Joint Forces MYP Multiyear procurement NDAA National Defense Authorization Act PEO Program Executive Office... steel to lower the ship’s center of gravity and counteract the radar’s additional weight. Significant upgrades to the ship’s electric plant and air...increasing steel on innerbottom scantlings (e.g., thickening the structural materials to redistribute weight for ship stability) • Widen stern—up to 4

  9. Ocean acidification mediates photosynthetic response to UV radiation and temperature increase in the diatom Phaeodactylum tricornutum

    Directory of Open Access Journals (Sweden)

    E. W. Helbling

    2012-10-01

    Full Text Available Increasing atmospheric CO2 concentration is responsible for progressive ocean acidification, ocean warming as well as decreased thickness of upper mixing layer (UML, thus exposing phytoplankton cells not only to lower pH and higher temperatures but also to higher levels of solar UV radiation. In order to evaluate the combined effects of ocean acidification, UV radiation and temperature, we used the diatom Phaeodactylum tricornutum as a model organism and examined its physiological performance after grown under two CO2 concentrations (390 and 1000 μatm for more than 20 generations. Compared to the ambient CO2 level (390 μatm, growth at the elevated CO2 concentration increased non-photochemical quenching (NPQ of cells and partially counteracted the harm to PS II (photosystem II caused by UV-A and UV-B. Such an effect was less pronounced under increased temperature levels. The ratio of repair to UV-B induced damage decreased with increased NPQ, reflecting induction of NPQ when repair dropped behind the damage, and it was higher under the ocean acidification condition, showing that the increased pCO2 and lowered pH counteracted UV-B induced harm. As for photosynthetic carbon fixation rate which increased with increasing temperature from 15 to 25 °C, the elevated CO2 and temperature levels synergistically interacted to reduce the inhibition caused by UV-B and thus increase the carbon fixation.

  10. Ocean acidification mediates photosynthetic response to UV radiation and temperature increase in the diatom Phaeodactylum tricornutum

    Directory of Open Access Journals (Sweden)

    E. W. Helbling

    2012-06-01

    Full Text Available Increasing atmospheric CO2 concentration is responsible for progressive ocean acidification, ocean warming as well as decreased thickness of upper mixing layer (UML, thus exposing phytoplankton cells not only to lower pH and higher temperatures but also to higher levels of solar UV radiation. In order to evaluate the combined effects of ocean acidification, UV radiation and temperature, we used the diatom Phaeodactylum tricornutum as a model organism and examined its physiological performance after grown under two CO2 concentrations (390 and 1000 µatm for more than 20 generations. Compared to the ambient CO2 level (390 µatm, growth at the elevated CO2 concentration increased non-photochemical quenching (NPQ of cells and partially counteracted the harm to PSII caused by UV-A and UV-B. Such an effect was less pronounced under increased temperature levels. As for photosynthetic carbon fixation, the rate increased with increasing temperature from 15 to 25 °C, regardless of their growth CO2 levels. In addition, UV-induced inhibition of photosynthesis was inversely correlated to temperature. The ratio of repair to UV-induced damage showed inverse relationship with increased NPQ, showing higher values under the ocean acidification condition against UV-B, reflecting that the increased pCO2 and lowered pH counteracted UV-B induced harm.

  11. Comparison of non-landslide sampling strategies to counteract inventory-based biases within national-scale statistical landslide susceptibility models

    Science.gov (United States)

    Lima, Pedro; Steger, Stefan; Glade, Thomas

    2017-04-01

    , composed by 14,519 shallow landslides. Within this study, we introduce the following explanatory variables to test the effect of different non-landslide strategies: Lithological units, grouped by their geotechnical properties and topographic parameters such as aspect, elevation, slope gradient and the topographic position. Landslide susceptibility maps will be derived by applying logistic regression, while systematic comparisons will be carried out based on models created by different non-landslide sampling strategies. Models generated by the conventional random sampling are presented against models based on stratified and clustered sampling strategies. The modelling results will be compared in terms of their prediction performance measured by the AUROC (Area Under the Receiver Operating Characteristic Curve) obtained by means of a k-fold cross-validation and also by the spatial pattern of the maps. The outcomes of this study are intended to contribute to the understanding on how landslide-inventory based biases may be counteracted.

  12. The causes analysis of clinical blood transfusion adverse reactions and counteractions%临床输血不良反应原因分析及对策

    Institute of Scientific and Technical Information of China (English)

    常洪劲; 许静静; 李岩

    2016-01-01

    Objective To analyze the possible reasons of blood transfusion adverse reactions and consti-tute the counteractions for further reducing or preventing similar blood transfusion adverse reactions.Methods The fifty-nine cases of blood transfusion adverse reactions and all the 44983 person-time of blood transfu-sion were collected between January 2013 and December 2014.And then we analyzed the time-lag,the inci-dence rate of BTAR in different blood products,the harm of the body from BTAR,department and patients’ outcome.Results All the BTAR occurred in the 6 hours in the beginning of blood transfusion, which were called acute transfusion reactions.Skin allergy and fervescence were the major symptoms of acute transfusion reaction.The blood products of blood transfusion adverse reactions included virus inactivated frozen plasma, platelets,cryoprecipitate, and suspended leukocyte reduced red blood cells.Among the blood products of transfusion adverse reactions,the BTAR incidence rate of plasma occupy the multiple.The ICU were the ma-jor department.After treatment, the damage caused by adverse reactions were recovered.Conclusion The occurrence of blood transfusion adverse reactions were mainly patients themselves allergic to immunoglobu-lin within the plasma,or the patients had produced leucocyte antibody.By symptomatic treatment,it was to give antiallergic drug and febrifuge before blood transfusion routinely and the antigen in coordination with each other and leukocyte reduced blood products which could reduce or avoid the occurrence of blood trans-fusion adverse reactions.%目的:分析发生输血不良反应( blood transfusion adverse reactions,BTAR)的可能原因并制订应对措施,进一步减少或避免类似BTAR的发生。方法收集2013年1月至2014年12月期间发生的BTAR 59例及所有输血人次44983人次,分析发生BTAR的时滞、不同血制品的不良反应发生率、不良反应对机体的危害、科室分布及患者预

  13. 逍遥散抗慢性心理应激海马神经元凋亡的机理研究%Mechanism of Xiaoyao Powder in Counteracting Apoptosis of Hippocampus Neurons Caused by Chronic Psychological Stress

    Institute of Scientific and Technical Information of China (English)

    王文竹; 杨忠华; 徐志伟; 苏俊芳

    2011-01-01

    Objective To investigate the effect of Xiaoyao Powder(XP) on apoptosis of hippocampus neurons and glucocorticoid receptor(GR) mRNA expression caused by chronic psychological stress. Methods Wistar rats were randomized to 3 groups: normal group(without any stimulation,gastric gavage of 2 mL normal saline per day), model group( chronic mild unpredictable stress, gastric gavage of 2 mL normal saline per day) and XP group(gastric gavage of 2 mL XP one hour before stress). The changes of body weight and sucrose preference were observed. The apoptotic rate of hippocampal neurons were detected by PI staining method and GR mRNA expression by in-situ hybridization.Results After treatment with chronic mild unpredictable stress for 21 days, the body weight as well as the weight gain was lower in the model group and XP group than that in the normal group(P < 0.01 ), and the sucrose preference was decreased in the model group (P < 0.01 ). In the model group, the apoptotic rate of hippocampal neurons was increased(P < 0.05), and GR mRNA expression was decreased(P < 0.01 ). XP decreased the apoptotic rate (P < 0.05) and increased GR mRNA expression(P < 0.01 ). Conclusion Chronic mild unpredictable stress can significantly decrease sucrose preference. XP can counteract the decrease of sucrose preference and significantly improve the apoptosis of hippocampus neurons caused by chronic psychological stress, which mechanism maybe related to the regulation of GR mRNA expression.%目的 观察逍遥散抗慢性心理应激海马神经元凋亡及糖皮质激素受体(GR)表达的影响.方法 Wistar 大鼠按体重分为正常组、模型组、逍遥散组.正常组及模型组灌胃等量生理盐水,逍遥散组给予逍遥散7.02g/kg.观察实验前后大鼠体重及糖水偏爱度的变化,采用PI法检测大鼠海马神经元凋亡,原位杂交法检测GR mrRNA表达.结果 经过21 d慢性轻度不可预计应激(CMUS)造模后,模型组、逍遥散组体重及

  14. 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.

  15. 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.

  16. Discuss the Cardiovascular Disease From "Fire Inter-restraining Metal Counter-action Fire"%从“火克金,金侮火”论治心血管疾病

    Institute of Scientific and Technical Information of China (English)

    瞿飞; 李爱华

    2011-01-01

    从中医藏象的生理、病理、临床3个方面及联系现代医学论述五行中“火克金,金侮火”的关系,从而丰富中医基础理论及指导心血管疾病临床防治均有一定意义.%To discuss the relation between "fire inter-restraining metal, counter-action fire through Zangxiang theory which focuses on the study of physiological functions, pathological changes, therapeutic effect and links the three discussed the five elements of modern medicine. There is a sense of enrich and guide prevention and treatment of cardiovascular diseases.

  17. Local food web management increases resilience and buffers against global change effects on freshwaters

    Science.gov (United States)

    Urrutia-Cordero, Pablo; Ekvall, Mattias K.; Hansson, Lars-Anders

    2016-07-01

    A major challenge for ecological research is to identify ways to improve resilience to climate-induced changes in order to secure the ecosystem functions of natural systems, as well as ecosystem services for human welfare. With respect to aquatic ecosystems, interactions between climate warming and the elevated runoff of humic substances (brownification) may strongly affect ecosystem functions and services. However, we hitherto lack the adaptive management tools needed to counteract such global-scale effects on freshwater ecosystems. Here we show, both experimentally and using monitoring data, that predicted climatic warming and brownification will reduce freshwater quality by exacerbating cyanobacterial growth and toxin levels. Furthermore, in a model based on long-term data from a natural system, we demonstrate that food web management has the potential to increase the resilience of freshwater systems against the growth of harmful cyanobacteria, and thereby that local efforts offer an opportunity to secure our water resources against some of the negative impacts of climate warming and brownification. This allows for novel policy action at a local scale to counteract effects of global-scale environmental change, thereby providing a buffer period and a safer operating space until climate mitigation strategies are effectively established.

  18. Effect of increased

    NARCIS (Netherlands)

    Carreira , C.; Heldal, M.; Bratbak, G.

    2013-01-01

    Atmospheric carbon dioxide (CO2) has increased since the pre-industrial period and is predicted to continue to increase throughout the twenty-first century. The ocean is a sink for atmospheric CO2 and increased CO2 concentration will change the carbonate equilibrium of seawater and result in lower c

  19. Increasing Mobility Confidence

    Science.gov (United States)

    ... Español In Your Area NPF Shop Increasing Mobility Confidence To increase your confidence moving, you have to move! Make Text Smaller ... It might seem counterintuitive, but to increase your confidence moving, you have to move! Build physical activity ...

  20. Depletion of regulatory T cells leads to an exacerbation of delayedtype hypersensitivity arthritis in C57BL/6 mice that can be counteracted by IL-17 blockade

    DEFF Research Database (Denmark)

    Atkinson, Sara Marie; Hoffmann, Ute; Bach, Emil

    2016-01-01

    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...

  1. Whey protein isolate counteracts the effects of a high-fat diet on energy intake and hypothalamic and adipose tissue expression of energy balance-related genes.

    Science.gov (United States)

    McAllan, Liam; Keane, Deirdre; Schellekens, Harriët; Roche, Helen M; Korpela, Riitta; Cryan, John F; Nilaweera, Kanishka N

    2013-12-14

    The intake of whey protein isolate (WPI) is known to reduce high-fat diet (HFD)-induced body-weight gain and adiposity. However, the molecular mechanisms are not fully understood. To this end, we fed C57BL/6J mice for 8 weeks with diets containing 10 % energy as fat (low-fat diet, LFD) or 45 % energy as fat (HFD) enriched with either 20 % energy as casein (LFD and HFD) or WPI (high-fat WPI). Metabolic parameters and the hypothalamic and epididymal adipose tissue expression of energy balance-related genes were investigated. The HFD increased fat mass and plasma leptin levels and decreased the dark-phase energy intake, meal number, RER, and metabolic (VO₂ and heat) and locomotor activities compared with the LFD. The HFD increased the hypothalamic tissue mRNA expression of the leptin receptor, insulin receptor (INSR) and carnitine palmitoyltransferase 1b (CPT1b). The HFD also reduced the adipose tissue mRNA expression of GLUT4 and INSR. In contrast, WPI reduced fat mass, normalised dark-phase energy intake and increased meal size in HFD-fed mice. The dietary protein did not have an impact on plasma leptin, insulin, glucose or glucagon-like peptide 1 levels, but increased plasma TAG levels in HFD-fed mice. At a cellular level, WPI significantly reduced the HFD-associated increase in the hypothalamic tissue mRNA expression of the leptin receptor, INSR and CPT1b. Also, WPI prevented the HFD-induced reduction in the adipose tissue mRNA expression of INSR and GLUT4. In comparison with casein, the effects of WPI on energy intake and hypothalamic and adipose tissue gene expression may thus represent a state of reduced susceptibility to weight gain on a HFD.

  2. Increasingly minimal bias routing

    Energy Technology Data Exchange (ETDEWEB)

    Bataineh, Abdulla; Court, Thomas; Roweth, Duncan

    2017-02-21

    A system and algorithm configured to generate diversity at the traffic source so that packets are uniformly distributed over all of the available paths, but to increase the likelihood of taking a minimal path with each hop the packet takes. This is achieved by configuring routing biases so as to prefer non-minimal paths at the injection point, but increasingly prefer minimal paths as the packet proceeds, referred to herein as Increasing Minimal Bias (IMB).

  3. 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.

  4. Carbocysteine counteracts the effects of cigarette smoke on cell growth and on the SIRT1/FoxO3 axis in bronchial epithelial cells.

    Science.gov (United States)

    Pace, E; Di Vincenzo, S; Ferraro, M; Bruno, A; Dino, P; Bonsignore, M R; Battaglia, S; Saibene, F; Lanata, L; Gjomarkaj, M

    2016-08-01

    Cigarette smoke may accelerate cellular senescence by increasing oxidative stress. Altered proliferation and altered expression of anti-aging factors, including SIRT1 and FoxO3, characterise cellular senescence. The effects of carbocysteine on the SIRT1/FoxO3 axis and on downstream molecular mechanisms in human bronchial epithelial cells exposed to cigarette smoke are largely unknown. Aim of this study was to explore whether carbocysteine modulated SIRT1/FoxO3 axis, and downstream molecular mechanisms associated to cellular senescence, in a bronchial epithelial cell line (16-HBE) exposed to cigarette smoke. 16HBE cells were stimulated with/without cigarette smoke extracts (CSE) and carbocysteine. Flow cytometry and clonogenic assay were used to assess cell proliferation; western blot analysis was used for assessing nuclear expression of SIRT1 and FoxO3. The nuclear co-localization of SIRT1 and FoxO3 was assessed by fluorescence microscopy. Beta galactosidase (a senescence marker) and SIRT1 activity were assessed by specific staining and colorimetric assays, respectively. ChiP Assay and flow cytometry were used for assessing survivin gene regulation and protein expression, respectively. CSE decreased cell proliferation, the nuclear expression of SIRT1 and FoxO3 and increased beta galactosidase staining. CSE, reduced SIRT1 activity and FoxO3 localization on survivin promoter thus increasing survivin expression. In CSE stimulated bronchial epithelial cells carbocysteine reverted these phenomena by increasing cell proliferation, and SIRT1 and FoxO3 nuclear expression, and by reducing beta galactosidase staining and survivin expression. The study shows for the first time that carbocysteine may revert some senescence processes induced by oxidative stress due to cigarette smoke exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Aldose reductase inhibition counteracts nitrosative stress and poly(ADP-ribose) polymerase activation in diabetic rat kidney and high-glucose-exposed human mesangial cells

    OpenAIRE

    Drel, Viktor R.; Pacher, Pal; Stevens, Martin J; Obrosova, Irina G.

    2006-01-01

    Both increased aldose reductase (AR) activity and oxidative/nitrosative stress have been implicated in the pathogenesis of diabetic nephropathy, but the relation between the two factors remains a subject of debate. This study evaluated the effects of AR inhibition on nitrosative stress and poly(ADP-ribose) polymerase (PARP) activation in diabetic rat kidney and high-glucose-exposed human mesangial cells. In animal experiments, control (C) and streptozotocin-diabetic (D) rats were treated with...

  6. A new approach to counteract bacteria resistance: a comparative study between moxifloxacin and a new moxifloxacin derivative in different model systems of bacterial membrane.

    Science.gov (United States)

    Lopes, Silvia C; Ribeiro, Carla; Gameiro, Paula

    2013-02-01

    New drug design has been one of the major challenges to combat bacterial resistance over the past decade. Conventional antibiotics act by destroying bacterial cell wall or by blocking biosynthetic pathways necessary for its survival. Unfortunately, there has been a fast increase in multiresistance, to several conventional antibiotics, in clinical bacterial strains. Previous studies have shown that metalloantibiotics, ternary complexes of antibiotic-metal-phenanthroline, present an increased potential as antimicrobial agents. In this work moxifloxacin, a fourth-generation quinolone, with a broad spectrum of action, and its copper ternary complex (metalloantibiotic) have been study by fluorescence spectroscopy. Partition coefficients were determined and showed that while free moxifloxacin exhibits the same behaviour independently of the lipidic system tested, the metalloantibiotic presents higher partition to liposomes, in a lipid composition-dependent way. These significant differences in the interaction of the metalloantibiotic with model bacteria membranes point out for a putative change in its uptake mechanism with increased drug-lipid interaction potentiating metalloantibiotic influx.

  7. Increasing SLEDed Linac Gradient

    Energy Technology Data Exchange (ETDEWEB)

    Farkas, Zoltan D

    2001-11-08

    This note will show how to increase the SLED [1] gradient by varying Q{sub e}, the external Q of the SLED cavity, by increasing its Q{sub 0} and by increasing the compression ratio. If varying the external Q is to be effective, then the copper losses should be small so that Q{sub 0} >> Q{sub e}. Methods of varying Q{sub e} will be indicated but no experimental data will be presented. If we increase the klystron pulse width from 3.5 to 5 {micro}S and increase Q{sub 0} from the present 100000 to 300000, then the gradient increases by 19% and the beam energy increases from 50 to 60 GeV. This note will also discuss SLED operation at 11424 MHz, the NLC frequency. Without Q{sub e} switching, using SLED at 11424 MHz increases the SLAC gradient from 21 MV/m to 34 MV/m, and at the same repetition rate, uses about 1/5 of rf average power. If we also double the compression ratio, we reach 47 MV/m and over 100 GeV beam energy.

  8. Does a dynamic chair increase office workers' movements? - Results from a combined laboratory and field study.

    Science.gov (United States)

    Grooten, Wilhelmus J A; Äng, Björn O; Hagströmer, Maria; Conradsson, David; Nero, Håkan; Franzén, Erika

    2017-04-01

    Dynamic chairs have the potential to facilitate movements that could counteract health problems associated with sedentary office work. This study aimed to evaluate whether a dynamic chair can increase movements during desk-based office work. Fifteen healthy subjects performed desk-based office work using a dynamic office chair and compared to three other conditions in a movement laboratory. In a field study, the dynamic office chair was studied during three working days using accelerometry. Equivocal results showed that the dynamic chair increased upper body and chair movements as compared to the conventional chair, but lesser movements were found compared to standing. No differences were found between the conditions in the field study. A dynamic chair may facilitate movements in static desk-based office tasks, but the results were not consistent for all outcome measures. Validation of measuring protocols for assessing movements during desk-based office work is warranted. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Towards increasing diversity for the relaying of LT Fountain Codes in Wireless Sensor Networks

    CERN Document Server

    Anya, Apavatjrut; Jaffrès-Runser, Katia; Comaniciu, Cristina; Gorce, Jean-Marie

    2010-01-01

    Diversity is a powerful means to increase the transmission performance of wireless communications. For the case of fountain codes relaying, it has been shown previously that introducing diversity is also beneficial since it counteracts transmission losses on the channel. Instead of simply hop-by-hop forwarding information, each sensor node diversifies the information flow using XOR combinations of stored packets. This approach has been shown to be efficient for random linear fountain codes. However, random linear codes exhibit high decoding complexity. In this paper, we propose diversity increased relaying strategies for the more realistic Luby Transform code in order to maintain high transmission performance with low decoding computational complexity in a linear network. Results are provided herein for a linear network assuming uniform imperfect channel states.

  10. Aldose reductase inhibition counteracts nitrosative stress and poly(ADP-ribose) polymerase activation in diabetic rat kidney and high-glucose-exposed human mesangial cells.

    Science.gov (United States)

    Drel, Viktor R; Pacher, Pal; Stevens, Martin J; Obrosova, Irina G

    2006-04-15

    Both increased aldose reductase (AR) activity and oxidative/nitrosative stress have been implicated in the pathogenesis of diabetic nephropathy, but the relation between the two factors remains a subject of debate. This study evaluated the effects of AR inhibition on nitrosative stress and poly(ADP-ribose) polymerase (PARP) activation in diabetic rat kidney and high-glucose-exposed human mesangial cells. In animal experiments, control (C) and streptozotocin-diabetic (D) rats were treated with/without the AR inhibitor fidarestat (F, 16 mg kg(-1) day(-1)) for 6 weeks starting from induction of diabetes. Glucose, sorbitol, and fructose concentrations were significantly increased in the renal cortex of D vs C (p diabetes-induced increase in kidney weight as well as nitrotyrosine (NT, a marker of peroxynitrite-induced injury and nitrosative stress), and poly(ADP-ribose) (a marker of PARP activation) accumulation, assessed by both immunohistochemistry and Western blot analysis, in glomerular and tubular compartments of the renal cortex. In vitro studies revealed the presence of both AR and PARP-1 in human mesangial cells, and none of these two variables were affected by high glucose or F treatment. Nitrosylated and poly(ADP-ribosyl)ated proteins (Western blot analysis) accumulated in cells cultured in 30 mM D-glucose (vs 5.55 mM glucose, p diabetic renal cortex and high-glucose-exposed human mesangial cells. These findings reveal new beneficial properties of the AR inhibitor F and provide the rationale for detailed studies of F on diabetic nephropathy.

  11. Increasing Public Expenditure

    National Research Council Canada - National Science Library

    Ammar Ben Zaed

    2015-01-01

    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...

  12. Increasing Public Library Productivity.

    Science.gov (United States)

    Samuelson, Howard

    1981-01-01

    Suggests ways of improving productivity for public libraries faced with increased accountability, dwindling revenues, and continuing inflation. Techniques described include work simplification, work analysis, improved management, and employee motivation. (RAA)

  13. Increased intracranial pressure

    Science.gov (United States)

    ... patient's bedside in an emergency room or hospital. Primary care doctors may sometimes spot early symptoms of increased intracranial pressure such as headache, seizures, or other nervous system problems. An MRI ...

  14. Bipedal stance exercise enhances antiresorption effects of estrogen and counteracts its inhibitory effect on bone formation in sham and ovariectomized rats.

    Science.gov (United States)

    Chen, J L; Yao, W; Frost, H M; Li, C Y; Setterberg, R B; Jee, W S

    2001-08-01

    In this study we employed a raised cage model in combination with estrogen to observe their effects on the proximal tibial metaphysis (PTM) and tibial shaft (TX) in sham-operated or ovariectomized rats. A total of 105 6-month-old female Sprague-Dawley rats were used in the study. Bilateral sham ovariectomy or ovariectomy was performed at day 0 and the rats were housed in normal height or raised cages (RCs) and injected subcutaneously twice per week with 10 microg/kg of 17beta-estradiol (E2) or vehicle for 4 and 8 weeks. Because the time course of bone loss or bone gain distribution was not uniform in the metaphyses of the tibia, we subdivided the PTM into three zones (medial, central, and lateral) to observe the different bone loss or bone gain patterns after ovariectomy and/or raised cages. We found that: (1) E2 alone did not alter bone area or architecture in sham rats, whereas RC alone increased trabecular thickness and area of PTM, but had no effects on TX; (2) Ovx induced most bone loss from the central zone of the PTM and endocortical surface of TX, accompanied by decreased trabecular number and increased bone resorption; (3) E2 alone prevented ovx-induced bone loss by preserving trabecular number and depressing bone resorption; (4) RC alone partially compensated for bone loss following ovx by thickening the surviving trabeculae in lateral and medial zones, and tended to stimulate bone formation and decrease bone resorption; and (5) RC plus E2 increased trabecular bone area by having an additive effect on bone resorption and bone turnover. RCs helped to prevent the depressive effect of estrogen on periosteal bone formation. In conclusion, early and rapid bone loss occurred in the central zone of the metaphysis and endocortical surface after ovx. Estrogen replacement therapy prevented this loss. Raised cages partially compensated for bone loss following ovx by thickening the trabeculae in the lateral area of the metaphysis and decreased endocortical erosion

  15. Dietary Mannan Oligosaccharides: Counteracting the Side Effects of Soybean Meal Oil Inclusion on European Sea Bass (Dicentrarchus labrax) Gut Health and Skin Mucosa Mucus Production?

    Science.gov (United States)

    Torrecillas, Silvia; Montero, Daniel; Caballero, Maria José; Pittman, Karin A.; Custódio, Marco; Campo, Aurora; Sweetman, John; Izquierdo, Marisol

    2015-01-01

    The main objective of this study was to assess the effects of 4 g kg−1 dietary mannan oligosaccharides (MOS) inclusion in soybean oil (SBO)- and fish oil (FO)-based diets on the gut health and skin mucosa mucus production of European sea bass juveniles after 8 weeks of feeding. Dietary MOS, regardless of the oil source, promoted growth. The intestinal somatic index was not affected, however dietary SBO reduced the intestinal fold length, while dietary MOS increased it. The dietary oil source fed produced changes on the posterior intestine fatty acid profiles irrespective of MOS dietary supplementation. SBO down-regulated the gene expression of TCRβ, COX2, IL-1β, TNFα, IL-8, IL-6, IL-10, TGFβ, and Ig and up-regulated MHCII. MOS supplementation up-regulated the expression of MHCI, CD4, COX2, TNFα, and Ig when included in FO-based diets. However, there was a minor up-regulating effect on these genes when MOS was supplemented in the SBO-based diet. Both dietary oil sources and MOS affected mean mucous cell areas within the posterior gut, however the addition of MOS to a SBO diet increased the mucous cell size over the values shown in FO fed fish. Dietary SBO also trends to reduce mucous cell density in the anterior gut relative to FO, suggesting a lower overall mucosal secretion. There are no effects of dietary oil or MOS in the skin mucosal patterns. Complete replacement of FO by SBO, modified the gut fatty acid profile, altered posterior gut-associated immune system (GALT)-related gene expression and gut mucous cells patterns, induced shorter intestinal folds and tended to reduce European sea bass growth. However, when combined with MOS, the harmful effects of SBO appear to be partially balanced by moderating the down-regulation of certain GALT-related genes involved in the functioning of gut mucous barrier and increasing posterior gut mucous cell diffusion rates, thus helping to preserve immune homeostasis. This denotes the importance of a balanced

  16. 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.

  17. Moderate exercise and chronic stress produce counteractive effects on different areas of the brain by acting through various neurotransmitter receptor subtypes: A hypothesis

    Directory of Open Access Journals (Sweden)

    Saha Asit K

    2006-09-01

    Full Text Available Abstract Background Regular, "moderate", physical exercise is an established non-pharmacological form of treatment for depressive disorders. Brain lateralization has a significant role in the progress of depression. External stimuli such as various stressors or exercise influence the higher functions of the brain (cognition and affect. These effects often do not follow a linear course. Therefore, nonlinear dynamics seem best suited for modeling many of the phenomena, and putative global pathways in the brain, attributable to such external influences. Hypothesis The general hypothesis presented here considers only the nonlinear aspects of the effects produced by "moderate" exercise and "chronic" stressors, but does not preclude the possibility of linear responses. In reality, both linear and nonlinear mechanisms may be involved in the final outcomes. The well-known neurotransmitters serotonin (5-HT, dopamine (D and norepinephrine (NE all have various receptor subtypes. The article hypothesizes that 'Stress' increases the activity/concentration of some particular subtypes of receptors (designated nts for each of the known (and unknown neurotransmitters in the right anterior (RA and left posterior (LP regions (cortical and subcortical of the brain, and has the converse effects on a different set of receptor subtypes (designated nth. In contrast, 'Exercise' increases nth activity/concentration and/or reduces nts activity/concentration in the LA and RP areas of the brain. These effects may be initiated by the activation of Brain Derived Neurotrophic Factor (BDNF (among others in exercise and its suppression in stress. Conclusion On the basis of this hypothesis, a better understanding of brain neurodynamics might be achieved by considering the oscillations caused by single neurotransmitters acting on their different receptor subtypes, and the temporal pattern of recruitment of these subtypes. Further, appropriately designed and planned experiments

  18. 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

  19. Exploding Increase of Population

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J.H. [Sunmoon University, Chonan (Korea)

    2002-03-01

    Until 1650, the population of the world did not increase properly. According to studies of the demography, the annual increase rate of the world population during 2500 years, from 850 B.C. to 1650 A.D., was just 0.07%. Currently, however, the world population, which has exceptionally rapidly increased from 1900, is more than 6 billion as of 2000. After World War II, especially, the increase rate of the population has risen to about 1.8%, so we can use the word, explosion of the population. The explosion of the population accompanies the increase of energy consumption. The energy production of every year cannot sufficiently meet the energy demand, so we can face the grand energy crisis someday. The date might be a someday after 2020. According to the future forecasting of Shell, one of the majors, the peak of oil supply will be between 2015 and 2020. Unless the alternative energy is developed, the whole world will suffer the serious oil crisis.

  20. Counteracting effect of TRPC1-associated Ca2+ influx on TNF-α-induced COX-2-dependent prostaglandin E2 production in human colonic myofibroblasts.

    Science.gov (United States)

    Hai, Lin; Kawarabayashi, Yasuhiro; Imai, Yuko; Honda, Akira; Inoue, Ryuji

    2011-08-01

    TNF-α-NF-κB signaling plays a central role in inflammation, apoptosis, and neoplasia. One major consequence of this signaling in the gut is increased production of prostaglandin E(2) (PGE(2)) via cyclooxygenase-2 (COX-2) induction in myofibroblasts, which has been reported to be dependent on Ca(2+). In this study, we explored a potential role of canonical transient receptor potential (TRPC) proteins in this Ca(2+)-mediated signaling using a human colonic myofibroblast cell line CCD-18Co. In CCD-18Co cell, treatment with TNF-α greatly enhanced Ca(2+) influx induced by store depletion along with increased cell-surface expression of TRPC1 protein (but not of the other TRPC isoforms) and induction of a Gd(3+)-sensitive nonselective cationic conductance. Selective inhibition of TRPC1 expression by small interfering RNA (siRNA) or functionally effective TRPC1 antibody targeting the near-pore region of TRPC1 (T1E3) antagonized the enhancement of store-dependent Ca(2+) influx by TNF-α, whereas potentiated TNF-α induced PGE(2) production. Overexpression of TRPC1 in CCD-18Co produced opposite consequences. Inhibitors of NF-κB (curcumin, SN-50) attenuated TNF-α-induced enhancement of TRPC1 expression, store-dependent Ca(2+) influx, and COX-2-dependent PGE(2) production. In contrast, inhibition of calcineurin-nuclear factor of activated T-cell proteins (NFAT) signaling by FK506 or NFAT Activation Inhibitor III enhanced the PGE(2) production without affecting TRPC1 expression and the Ca(2+) influx. Finally, the suppression of store-dependent Ca(2+) influx by T1E3 antibody or siRNA knockdown significantly facilitated TNF-α-induced NF-κB nuclear translocation. In aggregate, these results strongly suggest that, in colonic myofibroblasts, NF-κB and NFAT serve as important positive and negative transcriptional regulators of TNF-α-induced COX-2-dependent PGE(2) production, respectively, at the downstream of TRPC1-associated Ca(2+) influx.

  1. Inhibition of CD34+ cell migration by matrix metalloproteinase-2 during acute myocardial ischemia, counteracted by ischemic preconditioning [version 3; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Dominika Lukovic

    2017-02-01

    Full Text Available Background. Mobilization of bone marrow-origin CD34+ cells was investigated 3 days (3d after acute myocardial infarction (AMI with/without ischemic preconditioning (IP in relation to stromal-derived factor-1 (SDF-1α/ chemokine receptor type 4 (CXCR4 axis, to search for possible mechanisms behind insufficient cardiac repair in the first days post-AMI. Methods. Closed-chest reperfused AMI was performed by percutaneous balloon occlusion of the mid-left anterior descending (LAD coronary artery for 90min, followed by reperfusion in pigs. Animals were randomized to receive either IP initiated by 3x5min cycles of re-occlusion/re-flow prior to AMI (n=6 or control AMI (n=12. Blood samples were collected at baseline, 3d post-AMI, and at 1-month follow-up to analyse chemokines and mobilized CD34+ cells. To investigate the effect of acute hypoxia, SDF-1α and matrix metalloproteinase (MMP-2 in vitro were assessed, and a migration assay of CD34+ cells toward cardiomyocytes was performed. Results. Reperfused AMI induced significant mobilisation of CD34+ cells (baseline: 260±75 vs. 3d: 668±180; P<0.001 and secretion of MMP-2 (baseline: 291.83±53.40 vs. 3d: 369.64±72.89; P=0.011 into plasma, without affecting the SDF-1α concentration. IP led to the inhibition of MMP-2 (IP: 165.67±47.99 vs. AMI: 369.64±72.89; P=0.004 3d post-AMI, accompanied by increased release of SDF-1α (baseline: 23.80±12.36 vs. 3d: 45.29±11.31; P=0.05 and CXCR4 (baseline: 0.59±0.16 vs. 3d: 2.06±1.42; P=0.034, with a parallel higher level of mobilisation of CD34+ cells (IP: 881±126 vs. AMI: 668±180; P=0.026, compared to non-conditioned AMI. In vitro, CD34+ cell migration toward cardiomyocytes was enhanced by SDF-1α, which was completely abolished by 90min hypoxia and co-incubation with MMP-2. Conclusions. Non-conditioned AMI induces MMP-2 release, hampering the ischemia-induced increase in SDF-1α and CXCR4 by cleaving the SDF-1α/CXCR4 axis, with diminished mobilization of

  2. 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...... controls. Urinary orosomucoid was measured using a particle-enhanced immunoturbidimetric assay. Plasma interleukin-6 (IL-6), tissue plasminogen activator (tPA) and soluble intercellular adhesion molecule-1 (sICAM) were measured using ELISA. Endothelial function measured as vasodilatory capacity...... of the brachial artery and echocardiography were done in all participants. RESULTS: Patients with diabetes and increased UOER had subclinically increased serum orosomucoid (pprotein (CRP) (p

  3. N-Acetylcysteine counteracts oxidative stress and protects alveolar epithelial cells from lung contusion-induced apoptosis in rats with blunt chest trauma.

    Science.gov (United States)

    Topcu-Tarladacalisir, Yeter; Tarladacalisir, Taner; Sapmaz-Metin, Melike; Karamustafaoglu, Altemur; Uz, Yesim Hulya; Akpolat, Meryem; Cerkezkayabekir, Aysegul; Turan, Fatma Nesrin

    2014-08-01

    The aim of this study was to investigate the protective effects of N-acetylcysteine (NAC) on peroxidative and apoptotic changes in the contused lungs of rats following blunt chest trauma. The rats were randomly divided into three groups: control, contusion, and contusion + NAC. All the rats, apart from those in the control group, performed moderate lung contusion. A daily intramuscular NAC injection (150 mg/kg) was given immediately following the blunt chest trauma and was continued for two additional days following cessation of the trauma. Samples of lung tissue were taken in order to evaluate the tissue malondialdehyde (MDA) level, histopathology, and epithelial cell apoptosis using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and active caspase-3 immunostaining. In addition, we immunohistochemically evaluated the expression of surfactant protein D (SP-D) in the lung tissue. The blunt chest trauma-induced lung contusion resulted in severe histopathological injury, as well as an increase in the MDA level and in the number of cells identified on TUNEL assay together with active caspase-3 positive epithelial cells, but a decrease in the number of SP-D positive alveolar type 2 (AT-2) cells. NAC treatment effectively attenuated histopathologic, peroxidative, and apoptotic changes, as well as reducing alterations in SP-D expression in the lung tissue. These findings indicate that the beneficial effects of NAC administrated following blunt chest trauma is related to the regulation of oxidative stress and apoptosis.

  4. Regular and Moderate Exercise Counteracts the Decline of Antioxidant Protection but Not Methylglyoxal-Dependent Glycative Burden in the Ovary of Reproductively Aging Mice

    Science.gov (United States)

    Cordone, V.; Grannonico, M.; Cacchio, M.

    2016-01-01

    Population aging results in urgent needs of interventions aimed at ensuring healthy senescence. Exercise often results in healthy aging, yet many molecular mechanisms underlying such effects still need to be identified. We here investigated whether the age-dependent accumulation of oxidative and methylglyoxal- (MG-) related molecular damage could be delayed by moderate exercise in the mouse ovary, an organ that first exhibits impaired function with advancing age in mammals. CD1 female mice underwent two- or four-month treadmill-based running through the transition from adult to middle age, when ovaries show signs of senescence, and markers of protection against reactive oxygen species (ROS) and MG were measured. The long-term exercise reduced the protein oxidative damage in the ovaries (P < 0.01), and this was linked to the preservation of the glutathione peroxidase protection against ROS (P < 0.001), as well as to the increased glutathione availability (P < 0.001). Conversely, even though the age-related deactivation of the MG-targeting systems was partially prevented by the long-term running programme (P < 0.001), exercised mice were not protected from the age-dependent glycative burden. In summary, lately initiated regular and moderate exercise limited some changes occurring in the ovaries of middle-aged mice, and this might help to develop nonpharmacological cointerventions to reduce the vulnerability of mammalian ovaries towards redox dysfunctions. PMID:28116035

  5. Regular and Moderate Exercise Counteracts the Decline of Antioxidant Protection but Not Methylglyoxal-Dependent Glycative Burden in the Ovary of Reproductively Aging Mice

    Directory of Open Access Journals (Sweden)

    S. Falone

    2016-01-01

    Full Text Available Population aging results in urgent needs of interventions aimed at ensuring healthy senescence. Exercise often results in healthy aging, yet many molecular mechanisms underlying such effects still need to be identified. We here investigated whether the age-dependent accumulation of oxidative and methylglyoxal- (MG- related molecular damage could be delayed by moderate exercise in the mouse ovary, an organ that first exhibits impaired function with advancing age in mammals. CD1 female mice underwent two- or four-month treadmill-based running through the transition from adult to middle age, when ovaries show signs of senescence, and markers of protection against reactive oxygen species (ROS and MG were measured. The long-term exercise reduced the protein oxidative damage in the ovaries (P<0.01, and this was linked to the preservation of the glutathione peroxidase protection against ROS (P<0.001, as well as to the increased glutathione availability (P<0.001. Conversely, even though the age-related deactivation of the MG-targeting systems was partially prevented by the long-term running programme (P<0.001, exercised mice were not protected from the age-dependent glycative burden. In summary, lately initiated regular and moderate exercise limited some changes occurring in the ovaries of middle-aged mice, and this might help to develop nonpharmacological cointerventions to reduce the vulnerability of mammalian ovaries towards redox dysfunctions.

  6. The Combined Repetitive Oligopeptides of Clostridium difficile Toxin A Counteract Premature Cleavage of the Glucosyl-Transferase Domain by Stabilizing Protein Conformation

    Directory of Open Access Journals (Sweden)

    Alexandra Olling

    2014-07-01

    Full Text Available Toxin A (TcdA and B (TcdB from Clostridium difficile enter host cells by receptor-mediated endocytosis. A prerequisite for proper toxin action is the intracellular release of the glucosyltransferase domain by an inherent cysteine protease, which is allosterically activated by inositol hexaphosphate (IP6. We found that in in vitro assays, the C-terminally-truncated TcdA1–1065 was more efficient at IP6-induced cleavage compared with full-length TcdA. We hypothesized that the C-terminally-located combined repetitive oligopeptides (CROPs interact with the N-terminal part of the toxin, thereby preventing autoproteolysis. Glutathione-S-transferase (GST pull-down assays and microscale thermophoresis confirmed binding between the CROPs and the glucosyltransferase (TcdA1–542 or intermediate (TcdA1102–1847 domain of TcdA, respectively. This interaction between the N- and C-terminus was not found for TcdB. Functional assays revealed that TcdB was more susceptible to inactivation by extracellular IP6-induced cleavage. In vitro autoprocessing and inactivation of TcdA, however, significantly increased, either by acidification of the surrounding milieu or following exchange of its CROP domain by the homologous CROP domain of TcdB. Thus, TcdA CROPs contribute to the stabilization and protection of toxin conformation in addition to function as the main receptor binding domain.

  7. 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

  8. 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.

  9. Skeletal Muscle PGC-1β Signaling is Sufficient to Drive an Endurance Exercise Phenotype and to Counteract Components of Detraining in Mice.

    Science.gov (United States)

    Lee, Samuel; Leone, Teresa C; Rogosa, Lisa; Rumsey, John; Ayala, Julio; Coen, Paul M; Fitts, Robert H; Vega, Rick B; Kelly, Daniel P

    2017-03-07

    PPARgamma coactivator-1 (PGC-1) α; ;and β serve as master transcriptional regulators of muscle mitochondrial functional capacity and are capable of enhancing muscle endurance when overexpressed in mice. We sought to determine whether muscle-specific transgenic overexpression of PGC-1β affects the detraining response following endurance training. First, we established and validated a mouse exercise training/detraining protocol. Secondly, we found that overexpression of PGC-1β in skeletal muscle of sedentary mice fully recapitulated the training response using multiple physiological and gene expression endpoints. Lastly, overexpression of PGC-1β during the detraining period resulted in a partial prevention of the detraining response. Specifically, an increase in ΔVO2max was maintained in trained mice with muscle overexpression of PGC-1β 6 weeks after cessation of training. However, other detraining responses, including changes in running performance and in situ 1/2 relaxation time (a measure of contractility) were not affected by overexpression of PGC-1β. We conclude that while activation of muscle PGC-1β is sufficient to drive the complete endurance phenotype in sedentary mice, it only partially prevents the detraining response following exercise training suggesting that the process of endurance detraining involves mechanisms beyond the reversal of muscle autonomous mechanisms involved in endurance fitness. In addition, the protocol described here should be useful for assessing early-stage proof-of-concept interventions in pre-clinical models of muscle disuse atrophy.

  10. 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.

  11. Increasing mobile radiography productivity.

    Science.gov (United States)

    Wong, Edward; Lung, Ngan Tsz; Ng, Kris; Jeor, Patrick

    2013-01-01

    Mobile radiography using computed radiography (CR) cassettes is a common equipment combination with a workflow bottleneck limited by location of CR readers. Advent of direct digital radiography (DDR) mobile x-ray machines removes this limitation by immediate image review and quality control. Through the use of key performance indicators (KPIs), the increase in efficiency can be quantified.

  12. CyPPA, a positive SK3/SK2 modulator, reduces activity of dopaminergic neurons, inhibits dopamine release, and counteracts hyperdopaminergic behaviors induced by methylphenidate

    Directory of Open Access Journals (Sweden)

    Kjartan F. Herrik

    2012-02-01

    Full Text Available Dopamine (DA containing midbrain neurons play critical roles in several psychiatric and neurological diseases, including schizophrenia and attention deficit hyperactivity disorder (ADHD, and the substantia nigra pars compacta neurons selectively degenerate in Parkinson’s disease. Pharmacological modulation of DA receptors and transporters are well established approaches for treatment of DA-related disorders. Direct modulation of the DA system by influencing the discharge pattern of these autonomously firing neurons has yet to be exploited as a potential therapeutic strategy. Small conductance Ca2+-activated K+ channels (SK channels, in particular the SK3 subtype, are important in the physiology of DA neurons, and agents modifying SK channel activity could potentially affect DA-signaling and DA-related behaviors. Here we show that CyPPA (cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl-6-methyl-pyrimidin-4-yl]-amine, a subtype-selective positive modulator of SK channels (SK3 > SK2 >>> SK1, IK, decreased spontaneous firing rate, increased the duration of the apamin-sensitive, medium duration afterhyperpolarization (mAHP, and caused an activity-dependent inhibition of current-evoked action potentials in DA neurons from both mouse and rat midbrain slices. Using a immunohistochemically and pharmacologically validated DA release assay employing cultured DA neurons from rats, we show that CyPPA repressed DA release in a concentration-dependent manner with a maximal effect equal to the D2 receptor agonist quinpirole. In vivo studies revealed that systemic administration of CyPPA attenuated methylphenidate-induced hyperactivity and stereotypic behaviors in mice. Taken together, the data accentuate the important role played by SK3 channels in the physiology of DA neurons, and indicate that their facilitation by CyPPA profoundly influences physiological as well as pharmacologically induced hyperdopaminergic behavior.

  13. Highly Selective Cyclooxygenase-1 Inhibitors P6 and Mofezolac Counteract Inflammatory State both In Vitro and In Vivo Models of Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Rosa Calvello

    2017-06-01

    Full Text Available Activated microglia secrete an array of pro-inflammatory factors, such as prostaglandins, whose accumulation contributes to neuronal damages. Prostaglandin endoperoxide synthases or cyclooxygenases (COX-1 and COX-2, which play a critical role in the inflammation, are the pharmacological targets of non-steroidal anti-inflammatory drugs, used to treat pain and inflammation. Since it was reported that COX-1 is the major player in mediating the brain inflammatory response, the aim of this study was to evaluate the effects of highly selective COX-1 inhibitors, such as P6 and mofezolac, in neuroinflammation models. Lipopolysaccharide (LPS-activated mouse BV-2 microglial cells and LPS intracerebroventricular-injected mice as in vitro and in vivo neuroinflammation models, respectively, were used to probe the antiinflammatory efficacy of P6 and mofezolac. Both P6 and mofezolac reduce COX-1 expression in LPS-activated BV-2 cells. This reduction was accompanied with PGE2 release reduction and NF-kB activation downregulation. Coextensively, in the in vivo model, both glial fibrillary acidic protein and ionized calcium-binding adapter molecule-1 expression, two markers of inflammation, were reduced by mofezolac to a rank depending on the encephalon area analyzed. The increase of COX-1 expression observed in all the brain sections of LPS-treated mice was selectively downregulated by the in vivo treatment with mofezolac as well as PGE2 release and Ikβα phosphorylation amount assayed in the brain areas tested. These results indicate the capability of P6 and mofezolac to modulate the NF-kB signaling pathway, emphasizing the neuroprotective effect and therapeutic potential of COX-1 inhibitors in the control of neuroinflammatory diseases.

  14. Telmisartan counteracts TGF-β1 induced epithelial–to–mesenchymal transition via PPAR-γ in human proximal tubule epithelial cells

    Science.gov (United States)

    Chen, Yumin; Luo, Qiong; Xiong, Zibo; Liang, Wei; Chen, Li; Xiong, Zuying

    2012-01-01

    Chronic renal failure (CRF) mainly results from kidney fibrosis. Epithelial-to-mesenchymal transition (EMT) occurs in stressed tubular epithelial cells and contributes to renal fibrosis. Transforming growth factor-β1 (TGF-β1) has been shown to initiate and complete the whole EMT process. Peroxisome proliferators-activated receptor-γ (PPAR-γ) exerts anti-inflammatory, anti-fibrotic and vaculo-protective effects on different renal diseases. Telmisartan is a member of angiotensin II (Ang II) receptor blocker (ARB) family. Recent studies show that Telmisartan has a partial agonistic effect on PPAR-γ. Therefore, we tested the hypothesis that Telmisartan reverses the progression of induced EMT by TGF-β1 in cultured human renal proximal tubular epithelial (HK-2) cells. Cultured HK-2 cells were treated with TGF-β1 (3 ng/ml), a combination of TGF-β1 and Telmisartan (10-200umol/L) and a combination of TGF-β1, Telmisartan and GW9662, a PPAR-γ antagonist for 48 hours. EMT was determined by quantitative real-time PCR analysis of E-cadherin (E-cad), Connective Tissue Growth Factor (CTGF) and PPAR-γ transcript expression and immunocytochemical analysis of E-cad, α-Smooth Muscle Actin (α-SMA) and PPAR-γ protein expression. TGF-β1 induced phenotypic EMT in cultured HK-2 cell line via significantly reduced E-cad expression and significantly increased CTGF, α-SMA expression in association with the loss of epithelial morphology. Telmisartan reversed all EMT markers in a dose-dependent manner which was inhibited by PPAR antagonist GW9662. In the present study, it was suggested that Telmisartan attenuated TGF-β1 induced EMT by agonistic activation of PPAR-γ. PMID:22949934

  15. Nrf2 and NF-κB modulation by sulforaphane counteracts multiple manifestations of diabetic neuropathy in rats and high glucose-induced changes.

    Science.gov (United States)

    Negi, Geeta; Kumar, Ashutosh; Sharma, Shyam S

    2011-11-01

    High glucose driven reactive oxygen intermediates production and inflammatory damage are recognized contributors of nerve dysfunction and subsequent damage in diabetic neuropathy. Sulforaphane, a known chemotherapeutic agent holds a promise for diabetic neuropathy because of its dual antioxidant and anti-inflammatory activities. The present study investigated the effect of sulforaphane in streptozotocin (STZ) induced diabetic neuropathy in rats. For in vitro experiments neuro2a cells were incubated with sulforaphane in the presence of normal (5.5 mM) and high glucose (30 mM). For in vivo studies, sulforaphane (0.5 and 1 mg/kg) was administered six weeks post diabetes induction for two weeks. Motor nerve conduction velocity (MNCV), nerve blood flow (NBF) and pain behavior were improved and malondialdehyde (MDA) level was reduced by sulforaphane. Antioxidant effect of sulforaphane is derived from nuclear erythroid 2-related factor 2 (Nrf2) activation as demonstrated by increased expression of Nrf2 and downstream targets hemeoxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1) in neuro2a cells and sciatic nerve of diabetic animals. Nuclear factor-kappa B (NF-κB) inhibition seemed to be responsible for antiinflammatory activity of sulforaphane as there was reduction in NF-κB expression and IκB kinase (IKK) phosphorylation along with abrogation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression and tumor necrosis factor-α (TNF-α) and interleukine-6 (IL-6) levels. Here in this study we provide an evidence that sulforaphane is effective in reversing the various deficits in experimental diabetic neuropathy. This study supports the defensive role of Nrf2 in neurons under conditions of oxidative stress and also suggests that the NF-κB pathway is an important modulator of inflammatory damage in diabetic neuropathy.

  16. Ba-Wei-Di-Huang-Wan through its active ingredient loganin counteracts substance P-enhanced NF-κB/ICAM-1 signaling in rats with bladder hyperactivity.

    Science.gov (United States)

    Tsai, Wen-Hsin; Wu, Chung-Hsin; Cheng, Chen-Hung; Chien, Chiang-Ting

    2016-09-01

    Overt bladder afferent activation may exacerbate endogenous substance P (SP) release to induce intercellular adhesion molecule-1 (ICAM-1)-mediated inflammation and reactive oxygen species (ROS) production leading to hyperactive bladder. Ba-Wei-Die-Huang-Wan (BWDHW), a traditional Chinese medicine, has been used to treat lower urinary tract symptoms in patients by undefined mechanisms. We explored the possible mechanisms and the active components of BWDHW on exogenous SP-induced bladder hyperactivity. BWDHW contained six major components: loganin, paeoniflorin, 5-hydroxymethylfurfural, cinnamic acid, cinnamaldehyde, and paeonol by high-performance liquid chromatography. In urethane-anesthetized female Wistar rats, we evaluated transcystometrogram, pelvic afferent nerve activity by electrophysiologic recording techniques, ICAM-1 expression by Western blot and immunohistochemistry, ROS amount by an ultrasensitive chemiluminescence method and possible ROS sources from the different leukocytes by specific stains in SP-treated bladder. BWDHW and its major component loganin dose-dependently inhibited H2 O2 and HOCl activity in vitro. Intragastrical BWDHW (250 mg/kg) and loganin (5 mg/kg) twice daily for 2 weeks did not affect the baseline micturition parameters. Intra-arterial SP (20 µg/rat) through neurokinin-1 receptor activation increased voiding frequency (shortened intercontraction intervals), pelvic afferent nerve activity, bladder NF-κB/ICAM-1 expression, bladder ROS amount, neutrophils adhesion to venous endothelium, CD68 (monocyte/macrophage), and mast cell infiltration in the inflamed bladder. BWDHW and loganin pretreatment significantly depressed SP-enhanced pelvic afferent nerve activity, bladder NF-κB/ICAM-1 expression, leukocyte infiltration, and ROS amount, and subsequently improved bladder hyperactivity. In conclusion, our results suggest that BWDHW and its active component loganin improves bladder hyperactivity via inhibiting SP/neurokinin-1

  17. 地拓新对海洛因依赖者脱毒的疗效观察%A Clinical Observation of Counteracting Effect of Di Tuo Xin for Heroinism

    Institute of Scientific and Technical Information of China (English)

    张湘; 陈列; 杨隆保

    2001-01-01

    观察应用纯中药制剂地拓新胶囊对海洛因依赖者的脱毒疗效。结果表明,地拓新能确切改善睡眠 (平均5.83天),躯体依赖控制满意(平均5.73天),精神依赖基本消除,性功能逐渐恢复,戒毒后无稽延症 状,服用方便,未见明显不良反应。%The counteracting effect of Di Tuo Xin Capsule for heroinism was observed. The results showed that the preparation can improve sleeping(average in 5. 83 days), control somatic dependence(average in 5.73 days), basically eliminate spiritual dependence, gradually restore sexual function, elicit no post -abstinence symp toms, and is convenient for use without obvious adverse effect.

  18. Ground Surface Response to Geothermal Drilling and the Following Counteractions in Staufen im Breisgau (Germany Investigated by TerraSAR-X Time Series Analysis and Geophysical Modeling

    Directory of Open Access Journals (Sweden)

    Christin Lubitz

    2014-10-01

    Full Text Available The city of Staufen im Breisgau in southwest Germany suffers from a localized land uplift, which has occurred in the past six years in relation to geothermal drilling activities in 2007. So far, severe damages at 269 buildings have been recorded. The chemical transformation of anhydrite and water to gypsum, resulting in a volume increase, has been attributed as the cause of the uplift. Previous studies provide knowledge on the spatio-temporal displacement evolution from 2008 through 2011 using leveling and spaceborne Synthetic Aperture Radar Interferometry (InSAR measurements, but lack a detailed representation of vertical and horizontal displacement contributions as well as geophysical modeling. This study focuses not only on continued observation analysis from June 2011 through July 2013, but also on obtaining and evaluating horizontal displacements in Staufen based on combined analysis of TerraSAR-X satellite imagery from both ascending and descending orbits. Applying the Small BAseline Subset (SBAS approach a deceleration of annual cumulative line of sight (LOS uplift is observable from 13.8 cm ± 0.3 cm (July 2008–July 2009 to 3 cm ± 0.3 cm (July 2012–July 2013 within area of maximum deformation NNE of the drilling zone. Conducting displacement decomposition on ascending and descending data of a common period (October 2012 through July 2013 yields in an approximately symmetric east- and westward motion with maximum values approximately 1 cm and 1.4 cm, respectively. The joint inversion of ascending and descending InSAR data for the common period from October 2012 through July 2013 shows that a horizontal rectangular source with length, width and depth of 177 m ± 19 m, 69 m ± 15 m and 89 m ± 9 m, respectively, can satisfactorily model the observation. The amount of opening at depth shows a decrease in time by about 71% for the period 2011–2012 as compared to period 2008–2009.

  19. 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...... to the skill composition in the market, employee bargaining power and productivity. Further, when our model is subjected to skill-upgrading and changes in employee bargaining power, it is capable of predicting the recent changes observed in the Danish income distribution. In addition, the model emphasizes...... that shocks to the employees' relative productivity, i.e., skill-biased technological change, are unlikely to have caused the increase in income inequality....

  20. Pemex increasing offshore activity

    Energy Technology Data Exchange (ETDEWEB)

    Beachy, D.

    1985-05-01

    Although austere by boom-year standards, Mexico's National Energy Program for 1984-1988 calls for forty wildcats and 90 to 144 development wells off the coast, primarily in the prolific Campeche Bay area. Platform additions will include nine drilling platforms, each for twelve wells, and eight eight platforms to drill injection wells. Additionally, 7 production, 6 accomodation, 6 linkage and 8 compression platforms and 13 tetrapods will be installed. The main objectives of the plan are energy self-sufficiency through the turn of the century, and energy diversification, savings and productivity. The most controversial portion of Mexico's energy program is that calling for nuclear energy development. The energy program lists three basic goals in hydrocarbon production: continuing research on better techniques of secondary recovery; increasing capacity for refining primary and secondary crude products and improving production of heavy crudes; and increasing storage capacity and installing pipelines capable of carrying a greater volume of crude.

  1. Market Expects Demand Increase

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    In the recent releasing Textile Industry Invigorating Plan,"givingattention to both domestlc and overseas markets"is put into a keyposition.Under a series policies,such as increasing the tax rebaterate for textile and garment exports,and granting loan for SME,thefurther development of this industry is expectative.Otherwise,weshould know that it costs time for demand driving.This need ourpatients.The only questionis how much time we have to wait.

  2. Alarming increase in refugees.

    Science.gov (United States)

    1992-01-01

    Over the past decade and half there has been an alarming worldwide increase in refugees. The total rose form 2.8 million in 1976 to 8.2 million in 1980, to 17.3 million in 1990. Africa's refugees rose from 1.2 million in 1976 to 5.6 million in 1990. Asia's increase over this period was much more rapid--from a mere 180,000 to 8 million. In the Americas the numbers more than trebled, from 770,000 to 2.7 million. Europe was the smallest increase, from 570,000 to 894,000. International law defines a refugee as someone outside of their own country, who has a well-founded fear of persecution because of their political or religious beliefs or ethnic origin, and who cannot turn to their own country for protection. Most refugees are genuine by this definition. The increase reflects, in part, fallout from the cold war. Ethiopia, Mozambique and Angola accounted for almost 1/2 of Africa's refugees; Afghanistan alone for 3/4 of Asia's total. They fled, for the most part, from 1 poor country into another, where they added to shortages of land and fuelwood, and intensified environmental pressure. Malawi, 1 of the poorest countries in the world, is sheltering perhaps as many as 750,000 refugees from the war in Mozambique. But among these refugees--especially among those who turned to the rich countries for asylum--were an increasing number of people who were not suffering political persecution. Driven out of their homes by the collapse of their environment or economic despair, and ready to take any means to get across borders, they are a new category: economic and environmental refugees. The most spectacular attempts hit the television screens: the Vietnamese boat people, ships festooned with Albanians. Behind the headlines there was a growing tide of asylum seekers. The numbers rose 10-fold in Germany from 1983 to 1990. In Switzerland they multiplied by 4 times. In Europe, as a whole, they grew from 71,000 in 1983 to an estimated 550,000 in 1990. In 1990 the numbers threatened to

  3. Increasing Childhood Influenza Vaccination

    Science.gov (United States)

    Nowalk, Mary Patricia; Lin, Chyongchiou J.; Hannibal, Kristin; Reis, Evelyn C.; Gallik, Gregory; Moehling, Krissy K.; Huang, Hsin-Hui; Allred, Norma J.; Wolfson, David H.; Zimmerman, Richard K.

    2014-01-01

    Background Since the 2008 inception of universal childhood influenza vaccination, national rates have risen more dramatically among younger children than older children and reported rates across racial/ethnic groups are inconsistent. Interventions may be needed to address age and racial disparities to achieve the recommended childhood influenza vaccination target of 70%. Purpose To evaluate an intervention to increase childhood influenza vaccination across age and racial groups. Methods In 2011–2012, 20 primary care practices treating children were randomly assigned to Intervention and Control arms of a cluster randomized controlled trial to increase childhood influenza vaccination uptake using a toolkit and other strategies including early delivery of donated vaccine, in-service staff meetings, and publicity. Results The average vaccination differences from pre-intervention to the intervention year were significantly larger in the Intervention arm (n=10 practices) than the Control arm (n=10 practices), for children aged 2–8 years (10.2 percentage points (pct pts) Intervention vs 3.6 pct pts Control) and 9–18 years (11.1 pct pts Intervention vs 4.3 pct pts Control, p<0.05), for non-white children (16.7 pct pts Intervention vs 4.6 pct pts Control, p<0.001), and overall (9.9 pct pts Intervention vs 4.2 pct pts Control, p<0.01). In multi-level modeling that accounted for person- and practice-level variables and the interactions among age, race and intervention, the likelihood of vaccination increased with younger age group (6–23 months), white race, commercial insurance, the practice’s pre-intervention vaccination rate, and being in the Intervention arm. Estimates of the interaction terms indicated that the intervention increased the likelihood of vaccination for non-white children in all age groups and white children aged 9–18 years. Conclusions A multi-strategy intervention that includes a practice improvement toolkit can significantly improve influenza

  4. CHINA INCREASED PETROLEUM TAX

    Institute of Scientific and Technical Information of China (English)

    Mu Xueping

    2005-01-01

    @@ After half a year's gestation and adjustment, the State Administration of Taxation finally set new tax rate of petroleum resources. Notification issued by the Ministry of Finance and the State Administration of Taxation said the petroleum resources tax standard would be lifted nationwide, after the tax rate adjustment, tax on crude oil would be increased to RMB 14-30 yuan per ton and that on natural gas to RMB 7-15 yuan per thousand cubic meters. The new tax rate has been effective nationwide since July 1.

  5. Increasing Inflationary Pressure

    Institute of Scientific and Technical Information of China (English)

    Guo Yan

    2008-01-01

    @@ China's CPI rose to 8.7 percent in February after hitting 7.1 percent in January,creating a 12-year high,the National Bureau of Statistics said.The figure exceeded market expectations,as the Bank of China,the country's secondlargest lender,had predicted a rise of only 8.3 percent.The Consumer Price Index (CPI)is the main gauge of inflation,andthe high CPI over the last two months has put pressure on the government to take action to curb the price increases,and added even more diffculty to the task of reining in this year's inflation rate.

  6. Elenoside increases intestinal motility

    Institute of Scientific and Technical Information of China (English)

    E Navarro; SJ Alonso; R Navarro; J Trujillo; E Jorge

    2006-01-01

    AIM: To study the effects of elenoside, an arylnaphthalene lignan from Justicia hyssopifolia, on gastrointestinal motility in vivo and in vitro in rats.METHODS: Routine in vivo experimental assessments were catharsis index, water percentage of boluses,intestinal transit, and codeine antagonism. The groups included were vehicle control (propylene glycol-ethanolplant oil-tween 80), elenoside (i.p. 25 and 50 mg/kg),cisapride (i.p. 10 mg/kg), and codeine phosphate (intragastric route, 50 mg/kg). In vitro approaches used isolated rat intestinal tissues (duodenum, jejunum, and ileum). The effects of elenoside at concentrations of 3.2× 10-4, 6.4 × 10-4 and 1.2 × 10-3 mol/L, and cisapride at 10-6 mol/L were investigated.RESULTS: Elenoside in vivo produced an increase in the catharsis index and water percentage of boluses and in the percentage of distance traveled by a suspension of activated charcoal. Codeine phosphate antagonized the effect of 25 mg/kg of elenoside. In vitro, elenoside in duodenum, jejunum and ileum produced an initial decrease in the contraction force followed by an increase.Elenoside resulted in decreased intestinal frequency in duodenum, jejunum, and ileum. The in vitro and in vivo effects of elenoside were similar to those produced by cisapride.CONCLUSION: Elenoside is a lignan with an action similar to that of purgative and prokinetics drugs.Elenoside, could be an alternative to cisapride in treatment of gastrointestinal diseases as well as a preventive therapy for the undesirable gastrointestinal effects produced by opioids used for mild to moderate pain.

  7. Agglomeration in fluidized beds: detection and counteraction

    NARCIS (Netherlands)

    Bartels. M.

    2008-01-01

    Fluidized beds comprise a quantity of solid particles that is suspended by an upward flowing gas. They are used for a variety of processes in the chemical industry, such as catalytic reactions, drying, coating and energy conversion. A major problem in industrial practice is the occurrence of unwante

  8. Electrical stimulation counteracts muscle decline in seniors

    National Research Council Canada - National Science Library

    Kern, Helmut; Barberi, Laura; Löfler, Stefan; Sbardella, Simona; Burggraf, Samantha; Fruhmann, Hannah; Carraro, Ugo; Mosole, Simone; Sarabon, Nejc; Vogelauer, Michael; Mayr, Winfried; Krenn, Matthias; Cvecka, Jan; Romanello, Vanina; Pietrangelo, Laura; Protasi, Feliciano; Sandri, Marco; Zampieri, Sandra; Musaro, Antonio

    2014-01-01

    .... We addressed whether electrical stimulation (ES) is an alternative intervention to improve muscle recovery and defined the molecular mechanism associated with improvement in muscle structure and function...

  9. THE MAIN PROBLEM OF COUNTERACTION AGAINST CORRUPTION

    Directory of Open Access Journals (Sweden)

    Alexander Sergeevich Dilkov

    2015-01-01

    Full Text Available The article considers the problem of corruption. The experience of anti-corruption activities in various countries shows convincingly that to completely get rid of corruption is impossible, as any other social evil, with solid foundations in economic, social and political system of society. You can put a question only about how to reduce the scale of corruption to the socially acceptable level. Corruption infringes upon interests and constitutional rights of citizens, undermines the rule of law and democratic principles, suggests discrediting the activities of the state apparatus, distorts the principle of legality, hinders economic reforms and therefore requires detailed investigation with the scientific side to find the most effective ways of countering this phenomenon. Corruption can be done in different ways and methods. The conclusion that corruption is not only a form of criminal enrichment bureaucratic state apparatus, it has always been the main source of criminalization of social life, its degradation.Corruption is both a prerequisite and a consequence of the functioning of the shadow economy, strengthening property differentiation of the society, the fall of morals and degradation of the socio-political life.

  10. Can Autonomy Counteract Extremism in Traditional Education?

    Science.gov (United States)

    Resnick, David

    2008-01-01

    The very purpose of traditional--especially religious--education is to induct the young into a unique vision of reality. When the compelling religious vision conflicts with other visions, extremist confrontations may result. This paper explores ways to "square the circle" of the educational conundrum of how to educate for fervent commitment to…

  11. Counteracting ring formation in rotary kilns

    NARCIS (Netherlands)

    Pisaroni, M.; Sadi, R.; Lahaye, D.

    Avoiding the formation of rings in rotary kilns is an issue of primary concern to the cement production industry. We developed a numerical combustion model that revealed that in our case study rings are typically formed in zones of maximal radiative heat transfer. This local overheating causes the o

  12. Counteracting inflammation: a promising therapy in cachexia.

    Science.gov (United States)

    Argiles, Josep M; Lopez-Soriano, Francisco J; Busquets, Silvia

    2012-01-01

    Disease progression in cancer is dependent on the complex interaction between the tumor and the host inflammatory response. Indeed, both the tumor and the patient produce cytokines that act on multiple target sites such as bone marrow, myocytes, hepatocytes, adipocytes, endothelial cells, and neurons, where they produce a complex cascade of biological responses leading to the wasting associated with cachexia. The cytokines that have been involved in this cachectic response are TNF-α, IL-1, IL-6, and interferon-gamma. Interestingly, these cytokines share the same metabolic effects, and their activities are closely interrelated. In many cases these cytokines exhibit synergic effects when administered together. Therefore, therapeutic strategies- either nutritional or pharmacological-have been based on either blocking their synthesis or their action.

  13. Comparison of counteract compression properties of different ceramic crowns for implant abutment%不同基底材料的瓷修复体用于种植修复时抵抗压力载荷的比较

    Institute of Scientific and Technical Information of China (English)

    肖剑锐; 韩小宪; 林雪梅; 陈宇轩; 孔亮

    2012-01-01

    Objective To compare the counteract compression properties of different ceramic crowns for implant abutment. Methods Co-Cr alloy ceramic crowns, Titanium ceramic crowns, gold alloy ceramic crowns and whole ceramic crowns were made for the Ti-abutment and the abutment tooth in vitro (the control group). Cyclic loads were applied on the crowns and the Max loading frequencies were recorded when the ceramic showed cracks.Results The Max loading frequency in the abutment tooth crowns were 159.3±6.7,147.7±2.4,149.5±3.3 and 138.6±7.1 respectively, and those were 167.6±2.7,149.7±6.5,152.8±4.3 and 122.0±4.6 in the Ti-abutmenl crowns. The Co-Cr alloy ceramic crowns in Ti-abutment could endure more loading frequencies than in the abutment tooth (P<0.05), and the whole ceramic crowns showed the contrast (P<0.05). In the Ti-abutment, Co-Cr alloy ceramic crowns endured most loading frequencies, and the whole ceramic crowns showed the least (P<0.05). Conclusion For Ti-abutment, Co-Cr alloy ceramic crown showed the best counteract compression properties and whole ceramic crowns showed the worst.%目的 比较不同基底材料的瓷修复体用于种植修复时的抗压强度.方法 分别基于离体牙(对照组)和种植基台制作钴铬合金烤瓷、钛烤瓷、贵金属烤瓷(75%Au合金)和全瓷修复体,粘接后在咬合面进行循环加载,直至出现修复体瓷层破坏,记录最大加载次数.结果 四种修复体,用于离体基牙时出现破坏的最大加载次数(万次)分别为159.3±6.7,147.7±2.4,149.5±3.3和138.6±7.1;用于种植基台时分别为167.6±2.7,149.7±6.5,152.8±4.3和122.0±4.6.钴铬烤瓷修复用于种植基台时比用于离体基牙时可承受更多的加载次数(P<0.05),而全瓷修复体则相反(P<0.05);用于种植基台修复时,钴铬烤瓷承受加载次数较多,而全瓷修复体可承受的加载次数最少,均有统计学意义(P<0.05),钛烤瓷及贵金属烤瓷居中.结论 针对种植体基

  14. Increasing orUnderselling ?

    Institute of Scientific and Technical Information of China (English)

    Guo Yan

    2011-01-01

    The downgrade of sovereignty credit rating of the United States causes new concerns on US treasury bonds.According to the report issued recently by Treasury Ministry of United States,China as the largest oversea holding country of US treasury bonds continues to buy US treasury bonds,with an increase of 5.7 billion US dollars in June,marking the third month in line.Till now,China has US treasury bonds up to a new record of 1,165.5 billion US dollars,which amounts to 26% of the oversea holding US treasury bonds,based on market estimation,followed by Japan (20%),UK (8%),Brazil (5%)and Russia (3%).However,in sharp contrast to China,other countries are underselling us treasury bonds,particularly Russia.Data shows that since October 2010,Russia has been selling US treasury bonds for eight months in line,up to 38% of their holdings.Now Russia only holds 111 billion US dollars of US treasury bond.Why the countries take totally different attitudes towards to US treasury bonds? Tne reporter interviewed the experts from China and Russia for more details.

  15. Stress increases periodontal inflammation

    Science.gov (United States)

    RIVERA, CÉSAR; MONSALVE, FRANCISCO; SUAZO, IVÁN; BECERRA, JAVIERA

    2012-01-01

    This study aimed to examine the effect of chronic restraint stress (RS) on the severity of experimental periodontal disease in rats. A total of 32 male Sprague Dawley (SD) rats were divided into four groups: i) Rats receiving two treatment regimens, chronic stress induced by movement restriction in acrylic cylinders for 1–1.5 h daily and induction of experimental periodontal disease, using a nylon ligature which was placed around the first left mandibular molars (n=8); ii) induction of periodontal disease, without RS (n=8); iii) RS (n=8) and iv) control (n=8). After 15 days, blood samples were obtained, and blood glucose levels and the corticosterone concentration were measured as stress markers. The severity of periodontal disease was analyzed according to the level of gingival and bone inflammation, leading to compromise of the teeth involved. Chronic stress was induced with movement restriction (P≤0.05, Mann-Whitney U-test) and increased the severity (P≤0.05, Mann-Whitney U-test) of experimental perio dontal disease in rats, according to the level of gingival and bone inflammation around the first left mandibular molars. The results of the present study showed that RS modulates periodontal inflammation and that the rat model described herein is suitable for investigating the association between stress and periodontal disease. PMID:23226743

  16. Increasing Possibilities of Nanosuspension

    Directory of Open Access Journals (Sweden)

    Kumar Bishwajit Sutradhar

    2013-01-01

    Full Text Available 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, nanotechnology 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 nanotechnology. 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 nonoral administration. Here, this review describes the methods of pharmaceutical nanosuspension production including advantages and disadvantages, potential benefits, characterization tests, and pharmaceutical applications in drug delivery.

  17. The metabotropic glutamate 2/3 receptor agonist LY379268 counteracted ketamine-and apomorphine-induced performance deficits in the object recognition task, but not object location task, in rats.

    Science.gov (United States)

    Pitsikas, Nikolaos; Markou, Athina

    2014-10-01

    Experimental evidence indicates that the non competitive N-methyl-d-aspartate (NMDA) receptor antagonist ketamine and the mixed dopamine (DA) D1/D2 receptor agonist apomorphine induce schizophrenia-like symptoms in rodents, including cognitive deficits. Activation of Group II metabotropic glutamate 2/3 (mGlu2/3) receptors reduces the excessive glutamate release that is hypothesized to be associated with psychiatric disorders. Thus, mGlu2/3 receptor agonists may reverse deficits induced by excessive glutamate or DA release induced by administration of NMDA receptor antagonists and DA receptor agonists, respectively, and potentially those seen in schizophrenia. LY379268 is a selective mGlu2/3 receptor agonist that has shown to be effective in several animal models of stroke, epilepsy, and drug abuse. The present study investigated whether LY379268 antagonizes non-spatial and spatial recognition memory deficits induced by ketamine and apomorphine administration in rats. To assess the effects of the compounds on non-spatial and spatial recognition memory, the object recognition task and object location task were used. Post-training administration of LY379268 (1-3 mg/kg, i.p.) counteracted ketamine (3 mg/kg, i.p.) and apomorphine (1 mg/kg, i.p.)-induced performance deficits in the object recognition task. In contrast, LY379268 (1-3 mg/kg, i.p.) did not attenuate spatial recognition memory deficits produced by ketamine (3 mg/kg, i.p.) or apomorphine (1 mg/kg, i.p.) in the object location task. The present data show that the mGlu2/3 receptor agonist LY379268 reversed non-spatial, but not spatial, recognition memory deficits induced by NMDA receptor blockade or DA receptor agonism in rodents. Thus, such mGlu2/3 receptor agonists may be efficacious in reversing some memory deficits seen in schizophrenia patients.

  18. 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.

  19. Increased mortality in narcolepsy.

    Science.gov (United States)

    Ohayon, Maurice M; Black, Jed; Lai, Chinglin; Eller, Mark; Guinta, Diane; Bhattacharyya, Arun

    2014-03-01

    To evaluate the mortality rate in patients with narcolepsy. Data were derived from a large database representative of the US population, which contains anonymized patient-linked longitudinal claims for 173 million individuals. Symphony Health Solutions (SHS) Source Lx, an anonymized longitudinal patient dataset. All records of patients registered in the SHS database between 2008 and 2010. None. Identification of patients with narcolepsy was based on ≥ 1 medical claim with the diagnosis of narcolepsy (ICD-9 347.xx) from 2002 to 2012. Dates of death were acquired from the Social Security Administration via a third party; the third party information was encrypted in the same manner as the claims data such that anonymity is ensured prior to receipt by SHS. Annual all-cause mortality rates for 2008, 2009, and 2010 were calculated retrospectively for patients with narcolepsy and patients without narcolepsy in the database, and standardized mortality ratios (SMR) were calculated. Mortality rates were also compared with the general US population (Centers for Disease Control data). SMRs of the narcolepsy population were consistent over the 3-year period and showed an approximate 1.5-fold excess mortality relative to those without narcolepsy. The narcolepsy population had consistently higher mortality rates relative to those without narcolepsy across all age groups, stratified by age decile, from 25-34 years to 75+ years of age. The SMR for females with narcolepsy was lower than for males with narcolepsy. Narcolepsy was associated with approximately 1.5-fold excess mortality relative to those without narcolepsy. While the cause of this increased mortality is unknown, these findings warrant further investigation.

  20. Determinants of increased cardiovascular disease in obesity and metabolic syndrome.

    Science.gov (United States)

    Vazzana, N; Santilli, F; Sestili, S; Cuccurullo, C; Davi, G

    2011-01-01

    Obesity is associated with an increased mortality and morbidity for cardiovascular disease (CVD) and adipose tissue is recognised as an important player in obesity-mediated CVD. The diagnosis of the metabolic syndrome (MS) appears to identify substantial additional cardiovascular risk above and beyond the individual risk factors, even though the pathophysiology underlying this evidence is still unravelled. The inflammatory response related to fat accumulation may influence cardiovascular risk through its involvement not only in body weight homeostasis, but also in coagulation, fibrinolysis, endothelial dysfunction, insulin resistance (IR) and atherosclerosis. Moreover, there is evidence that oxidative stress may be a mechanistic link between several components of MS and CVD, through its role in inflammation and its ability to disrupt insulin-signaling. The cross-talk between impaired insulin-signaling and inflammatory pathways enhances both metabolic IR and endothelial dysfunction, which synergize to predispose to CVD. Persistent platelet hyperreactivity/activation emerges as the final pathway driven by intertwined interactions among IR, adipokine release, inflammation, dyslipidemia and oxidative stress and provides a pathophysiological explanation for the excess risk of atherothrombosis in this setting. Despite the availability of multiple interventions to counteract these metabolic changes, including appropriate diet, regular exercise, antiobesity drugs and bariatric surgery, relative failure to control the incidence of MS and its complications reflects both the multifactorial nature of these diseases as well as the scarce compliance of patients to established strategies. Evaluation of the impact of these therapeutic strategies on the pathobiology of atherothrombosis, as discussed in this review, will translate into an optimized approach for cardiovascular prevention.

  1. 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.

  2. Increases in Physical Activity Result in Diminishing Increments in Daily Energy Expenditure in Mice.

    Science.gov (United States)

    O'Neal, Timothy J; Friend, Danielle M; Guo, Juen; Hall, Kevin D; Kravitz, Alexxai V

    2017-02-06

    Exercise is a common component of weight loss strategies, yet exercise programs are associated with surprisingly small changes in body weight [1-4]. This may be due in part to compensatory adaptations, in which calories expended during exercise are counteracted by decreases in other aspects of energy expenditure [1, 5-10]. Here we examined the relationship between a rodent model of voluntary exercise- wheel running- and total daily energy expenditure. Use of a running wheel for 3 to 7 days increased daily energy expenditure, resulting in a caloric deficit of ∼1 kcal/day; however, total daily energy expenditure remained stable after the first week of wheel access, despite further increases in wheel use. We hypothesized that compensatory mechanisms accounted for the lack of increase in daily energy expenditure after the first week. Supporting this idea, we observed a decrease in off-wheel ambulation when mice were using the wheels, indicating behavioral compensation. Finally, we asked whether individual variation in wheel use within a group of mice would be associated with different levels of daily energy expenditure. Despite a large variation in wheel running, we did not observe a significant relationship between the amount of daily wheel running and total daily energy expenditure or energy intake across mice. Together, our experiments support a model in which the transition from sedentary to light activity is associated with an increase in daily energy expenditure, but further increases in physical activity produce diminishingly small increments in daily energy expenditure.

  3. 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.

  4. Brown world forests: increased ungulate browsing keeps temperate trees in recruitment bottlenecks in resource hotspots.

    Science.gov (United States)

    Churski, Marcin; Bubnicki, Jakub W; Jędrzejewska, Bogumiła; Kuijper, Dries P J; Cromsigt, Joris P G M

    2017-04-01

    Plant biomass consumers (mammalian herbivory and fire) are increasingly seen as major drivers of ecosystem structure and function but the prevailing paradigm in temperate forest ecology is still that their dynamics are mainly bottom-up resource-controlled. Using conceptual advances from savanna ecology, particularly the demographic bottleneck model, we present a novel view on temperate forest dynamics that integrates consumer and resource control. We used a fully factorial experiment, with varying levels of ungulate herbivory and resource (light) availability, to investigate how these factors shape recruitment of five temperate tree species. We ran simulations to project how inter- and intraspecific differences in height increment under the different experimental scenarios influence long-term recruitment of tree species. Strong herbivore-driven demographic bottlenecks occurred in our temperate forest system, and bottlenecks were as strong under resource-rich as under resource-poor conditions. Increased browsing by herbivores in resource-rich patches strongly counteracted the increased escape strength of saplings in these patches. This finding is a crucial extension of the demographic bottleneck model which assumes that increased resource availability allows plants to more easily escape consumer-driven bottlenecks. Our study demonstrates that a more dynamic understanding of consumer-resource interactions is necessary, where consumers and plants both respond to resource availability.

  5. Fibrinogen γ' increases the sensitivity to activated protein C in normal and factor V Leiden plasma.

    Science.gov (United States)

    Omarova, Farida; Uitte de Willige, Shirley; Simioni, Paolo; Ariëns, Robert A S; Bertina, Rogier M; Rosing, Jan; Castoldi, Elisabetta

    2014-08-28

    Activated protein C (APC) resistance, often associated with the factor V (FV) Leiden mutation, is the most common risk factor for venous thrombosis. We observed increased APC resistance in carriers of fibrinogen γ gene (FGG) haplotype 2, which is associated with reduced levels of the alternatively spliced fibrinogen γ' chain. This finding prompted us to study the effects of fibrinogen and its γ' chain on APC resistance. Fibrinogen, and particularly the γA/γ' isoform, improved the response of plasma to added APC in the thrombin generation-based assay. Similarly, a synthetic peptide mimicking the C-terminus of the fibrinogen γ' chain, which binds thrombin and inhibits its activities, greatly increased the APC sensitivity of normal and FV Leiden plasma, likely due to its ability to inhibit thrombin-mediated activation of FV and FVIII. Although the fibrinogen γ' peptide also inhibited protein C activation by the thrombin/thrombomodulin complex, it still increased the sensitivity of plasma to endogenously formed APC when thrombin generation was measured in the presence of soluble thrombomodulin. We conclude that fibrinogen, and particularly fibrinogen γ', increases plasma APC sensitivity. The fibrinogen γ' peptide might form the basis for pharmacologic interventions to counteract APC resistance. © 2014 by The American Society of Hematology.

  6. Role of PU.1 in MHC Class II Expression via CIITA Transcription in Plasmacytoid Dendritic Cells.

    Science.gov (United States)

    Miura, Ryosuke; Kasakura, Kazumi; Nakano, Nobuhiro; Hara, Mutsuko; Maeda, Keiko; Okumura, Ko; Ogawa, Hideoki; Yashiro, Takuya; Nishiyama, Chiharu

    2016-01-01

    The cofactor CIITA is a master regulator of MHC class II expression and several transcription factors regulating the cell type-specific expression of CIITA have been identified. Although the MHC class II expression in plasmacytoid dendritic cells (pDCs) is also mediated by CIITA, the transcription factors involved in the CIITA expression in pDCs are largely unknown. In the present study, we analyzed the role of a hematopoietic lineage-specific transcription factor, PU.1, in CIITA transcription in pDCs. The introduction of PU.1 siRNA into mouse pDCs and a human pDC cell line, CAL-1, reduced the mRNA levels of MHC class II and CIITA. When the binding of PU.1 to the 3rd promoter of CIITA (pIII) in CAL-1 and mouse pDCs was analyzed by a chromatin immunoprecipitation assay, a significant amount of PU.1 binding to the pIII was detected, which was definitely decreased in PU.1 siRNA-transfected cells. Reporter assays showed that PU.1 knockdown reduced the pIII promoter activity and that three Ets-motifs in the human pIII promoter were candidates of cis-enhancing elements. By electrophoretic mobility shift assays, it was confirmed that two Ets-motifs, GGAA (-181/-178) and AGAA (-114/-111), among three candidates, were directly bound with PU.1. When mouse pDCs and CAL-1 cells were stimulated by GM-CSF, mRNA levels of PU.1, pIII-driven CIITA, total CIITA, MHC class II, and the amount of PU.1 binding to pIII were significantly increased. The GM-CSF-mediated up-regulation of these mRNAs was canceled in PU.1 siRNA-introduced cells. Taking these results together, we conclude that PU.1 transactivates the pIII through direct binding to Ets-motifs in the promoter in pDCs.

  7. 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

    BACKGROUND: Hormonal fluctuations during the menstrual cycle influence energy intake and expenditure as well as eating preferences and behavior. OBJECTIVE: We examined the impact of a diet and exercise weight-loss program that was designed to target and moderate the effects of the menstrual cycle...... 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....... 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...

  8. Heteroresistance to Itraconazole Alters the Morphology and Increases the Virulence of Cryptococcus gattii.

    Science.gov (United States)

    Ferreira, Gabriella Freitas; Santos, Julliana Ribeiro Alves; Costa, Marliete Carvalho da; Holanda, Rodrigo Assunção de; Denadai, Ângelo Márcio Leite; Freitas, Gustavo José Cota de; Santos, Áquila Rodrigues Costa; Tavares, Priscila Batista; Paixão, Tatiane Alves; Santos, Daniel Assis

    2015-08-01

    Cryptococcus gattii is the main etiological agent of cryptococcosis in immunocompetent individuals. The triazole drug itraconazole is one of the antifungals used to treat patients with cryptococcosis. Heteroresistance is an adaptive mechanism to counteract the stress of increasing drug concentrations, and it can enhance the ability of a microorganism to survive under antifungal pressure. In this study, we evaluated the ability of 11 C. gattii strains to develop itraconazole heteroresistance. Heteroresistant clones were analyzed for drug susceptibility, alterations in cell diameter, capsule properties, and virulence in a murine model. Heteroresistance to itraconazole was intrinsic in all of the strains analyzed, reduced both the capsule size and the cell diameter, induced molecular heterogeneity at the chromosomal level, changed the negatively charged cells, reduced ergosterol content, and improved the antioxidant system. A positive correlation between surface/volume ratio of original cells and the level of heteroresistance to itraconazole (LHI) was observed in addition to a negative correlation between capsule size of heteroresistant clones and LHI. Moreover, heteroresistance to itraconazole increased the engulfment of C. gattii by macrophages and augmented fungal proliferation inside these cells, which probably accounted for the reduced survival of the mice infected with the heteroresistant clones and the higher fungal burden in lungs and brain. Our results indicate that heteroresistance to itraconazole is intrinsic and increases the virulence of C. gattii. This phenomenon may represent an additional mechanism that contributes to relapses of cryptococcosis in patients during itraconazole therapy.

  9. Overexpression of a Drosophila homolog of apolipoprotein D leads to increased stress resistance and extended lifespan.

    Science.gov (United States)

    Walker, David W; Muffat, Julien; Rundel, Colin; Benzer, Seymour

    2006-04-01

    Increased Apolipoprotein D (ApoD) expression has been reported in various neurological disorders, including Alzheimer's disease, schizophrenia, and stroke, and in the aging brain . However, whether ApoD is toxic or a defense is unknown. In a screen to identify genes that protect Drosophila against acute oxidative stress, we isolated a fly homolog of ApoD, Glial Lazarillo (GLaz). In independent transgenic lines, overexpression of GLaz resulted in increased resistance to hyperoxia (100% O(2)) as well as a 29% extension of lifespan under normoxia. These flies also displayed marked improvements in climbing and walking ability after sublethal exposure to hyperoxia. Overexpression of Glaz also increased resistance to starvation without altering lipid or protein content. To determine whether GLaz might be important in protection against reperfusion injury, we subjected the flies to hypoxia, followed by recovery under normoxia. Overexpression of GLaz was protective against behavioral deficits caused in normal flies by this ischemia/reperfusion paradigm. This and the accompanying paper by Sanchez et al. (in this issue of Current Biology) are the first to manipulate the levels of an ApoD homolog in a model organism. Our data suggest that human ApoD may play a protective role and thus may constitute a therapeutic target to counteract certain neurological diseases.

  10. 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

  11. Effects of shrub and tree cover increase on the near-surface atmosphere in northern Fennoscandia

    Science.gov (United States)

    Rydsaa, Johanne H.; Stordal, Frode; Bryn, Anders; Tallaksen, Lena M.

    2017-09-01

    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.

  12. High Blood Pressure Increasing Worldwide

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_162977.html High Blood Pressure Increasing Worldwide And health risks may appear even ... of people around the world with elevated or high blood pressure increases, so do the number of deaths linked ...

  13. Does residual force enhancement increase with increasing stretch magnitudes?

    Science.gov (United States)

    Hisey, Brandon; Leonard, Tim R; Herzog, Walter

    2009-07-22

    It is generally accepted that force enhancement in skeletal muscles increases with increasing stretch magnitudes. However, this property has not been tested across supra-physiological stretch magnitudes and different muscle lengths, thus it is not known whether this is a generic property of skeletal muscle, or merely a property that holds for small stretch magnitudes within the physiological range. Six cat soleus muscles were actively stretched with magnitudes varying from 3 to 24 mm at three different parts of the force-length relationship to test the hypothesis that force enhancement increases with increasing stretch magnitude, independent of muscle length. Residual force enhancement increased consistently with stretch amplitudes on the descending limb of the force-length relationship up to a threshold value, after which it reached a plateau. Force enhancement did not increase with stretch amplitude on the ascending limb of the force-length relationship. Passive force enhancement was observed for all test conditions, and paralleled the behavior of the residual force enhancement. Force enhancement increased with stretch magnitude when stretching occurred at lengths where there was natural passive force within the muscle. These results suggest that force enhancement does not increase unconditionally with increasing stretch magnitude, as is generally accepted, and that increasing force enhancement with stretch appears to be tightly linked to that part of the force-length relationship where there is naturally occurring passive force.

  14. Enhanced Locomotor Activity Is Required to Exert Dietary Restriction-Dependent Increase of Stress Resistance in Drosophila

    Directory of Open Access Journals (Sweden)

    Saurav Ghimire

    2015-01-01

    Full Text Available Dietary restriction (DR is known to be one of the most effective interventions to increase stress resistance, yet the mechanisms remain elusive. One of the most obvious DR-induced changes in phenotype is an increase in locomotor activity. Although it is conceptually perceivable that nutritional scarcity should prompt enhanced foraging behavior to garner additional dietary resources, the significance of enhanced movement activity has not been associated with the DR-dependent increase of stress resistance. In this study, we confirmed that flies raised on DR exhibited enhanced locomotive activity and increased stress resistance. Excision of fly wings minimized the DR-induced increase in locomotive activity, which resulted in attenuation of the DR-dependent increase of stress resistance. The possibility that wing clipping counteracts the DR by coercing flies to have more intake was ruled out since it did not induce any weight gain. Rather it was found that elimination of reactive oxygen species (ROS that is enhanced by DR-induced upregulation of expression of antioxidant genes was significantly reduced by wing clipping. Collectively, our data suggests that DR increased stress resistance by increasing the locomotor activity, which upregulated expression of protective genes including, but not limited to, ROS scavenger system.

  15. Enhanced Locomotor Activity Is Required to Exert Dietary Restriction-Dependent Increase of Stress Resistance in Drosophila.

    Science.gov (United States)

    Ghimire, Saurav; Kim, Man Su

    2015-01-01

    Dietary restriction (DR) is known to be one of the most effective interventions to increase stress resistance, yet the mechanisms remain elusive. One of the most obvious DR-induced changes in phenotype is an increase in locomotor activity. Although it is conceptually perceivable that nutritional scarcity should prompt enhanced foraging behavior to garner additional dietary resources, the significance of enhanced movement activity has not been associated with the DR-dependent increase of stress resistance. In this study, we confirmed that flies raised on DR exhibited enhanced locomotive activity and increased stress resistance. Excision of fly wings minimized the DR-induced increase in locomotive activity, which resulted in attenuation of the DR-dependent increase of stress resistance. The possibility that wing clipping counteracts the DR by coercing flies to have more intake was ruled out since it did not induce any weight gain. Rather it was found that elimination of reactive oxygen species (ROS) that is enhanced by DR-induced upregulation of expression of antioxidant genes was significantly reduced by wing clipping. Collectively, our data suggests that DR increased stress resistance by increasing the locomotor activity, which upregulated expression of protective genes including, but not limited to, ROS scavenger system.

  16. 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.

    2007-01-01

    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 c

  17. Low dose of corticosterone treatment with exercise increases hippocampal cell proliferation, and improves cognition

    Institute of Scientific and Technical Information of China (English)

    Suk-Yu Yau; Jada Chia-Di Lee; Benson Wui-Man Lau; Tatia M.C. Lee; Yick-Pang Ching; Siu-Wa Tang; Kwok-Fai So

    2011-01-01

    Intermediate level of stress is beneficial for brain functions, whereas extreme low level or high level of stress is deleterious. We have previously shown that chronic exposure to high doses of corticosterone (CORT) suppressed hippocampal plasticity and physical exercise in terms of running counteracted the detrimental effects of CORT treatment. We aimed to study whether a mild stress, that mimicked by a treatment with low CORT dose, improved hippocampal plasticity in terms of hippocampal cell proliferation and dendritic remodeling, and to examine whether running with CORT treatment showed an additive effect on improving hippocampal plasticity. The rats were treated with 20 mg/kg CORT for 14 days with or without running, followed by Morris water maze test or forced swim test. The hippocampal proliferating cells was labeled by intraperitoneal injection of 5-bromo-2'-deoxyuridine. The dendritic morphology was analyzed using Golgi staining method. Treatment with 20 mg/kg CORT alone yielded a higher number of hippocampal cell proliferation and significantly increased dendritic branching compared to vehicle-treated non-runners, but had no behavioral effects. In contrast, CORT treatment with running showed an additive increase in hippocampal cell proliferation and dendritic remodeling that was associated with improved spatial learning and decreased depression-like behavior; however, there was no additive improvement in behavior compared to vehicle-treated runners. These findings suggest that mild stress does not always cause detrimental effect on the brain, and combining mild stress with running could promote hippocampal plasticity via inducing cell proliferation and dendritic remodeling.

  18. 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.

  19. Korea's 2015 cigarette tax increases.

    Science.gov (United States)

    Cherukupalli, Rajeev

    2016-03-01

    South Korea increased tobacco taxes in 2015 after a 10-year gap. This commentary suggests two lessons for public finance practitioners. Substantive tax increases are crucial to reducing tobacco use; particularly where prices are demonstrably lower and prevalence higher in comparison to other countries ranked similarly on economic development indicators. Second, as a rule of thumb, governments cannot afford to neglect the annual increases that ensure that tobacco taxes do not lose their efficacy over time.

  20. 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.

  1. RESTAURANT NO. 2: PRICE INCREASES

    CERN Multimedia

    2003-01-01

    'DSR', the concession holder of Restaurant no. 2 (bldg. 504 - Meyrin site), has submitted to the Restaurant Supervisory Committee a request to increase certain prices. After close examination, the Committee has established that the proposed increases are compatible with the relevant price indexing mechanisms and other contractual conditions. The new prices will apply as from Monday, June 30, 2003.

  2. RESTAURANT NO. 3: PRICE INCREASES

    CERN Multimedia

    2003-01-01

    'AVENANCE', the concession holder of Restaurant no. 3 (bldg. 866 - Prévessin site), has submitted to the Restaurant Supervisory Committee a request to increase its prices. After close examination, the Committee has established that the proposed increases are compatible with the relevant price indexing mechanisms and other contractual conditions. The new prices will apply as from Monday, June 2, 2003.

  3. 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.

  4. 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.

  5. Volatiles Which Increase Magma Viscosity

    Science.gov (United States)

    Webb, S.

    2015-12-01

    The standard model of an erupting volcano is one in which the viscosity of a decompressing magma increases as the volatiles leave the melt structure to form bubbles. It has now been observed that the addition of the "volatiles" P, Cl and F result in an increase in silicate melt viscosity. This observation would mean that the viscosity of selected degassing magmas would decrease rather than increase. Here we look at P, Cl and F as three volatiles which increase viscosity through different structural mechanisms. In all three cases the volatiles increase the viscosity of peralkaline composition melts, but appear to always decrease the viscosity of peraluminous melts. Phosphorus causes the melt to unmix into a Na-P rich phase and a Na-poor silicate phase. Thus as the network modifying Na (or Ca) are removed to the phosphorus-rich melt, the matrix melt viscosity increases. With increasing amounts of added phosphorus (at network modifying Na ~ P) the addition of further phosphorus causes a decrease in viscosity. The addition of chlorine to Fe-free aluminosilicate melts results in an increase in viscosity. NMR data on these glass indicates that the chlorine sits in salt-like structures surrounded by Na and/or Ca. Such structures would remove network-modifying atoms from the melt structure and thus result in an increase in viscosity. The NMR spectra of fluorine-bearing glasses shows that F takes up at least 5 different structural positions in peralkaline composition melts. Three of these positions should result in a decrease in viscosity due to the removal of bridging oxygens. Two of the structural positons of F, however, should result in an increase in viscosity as they require the removal of network-modifying atoms from the melt structure (with one of the structures being that observed for Cl). This would imply that increasing amounts of F might result in an increase in viscosity. This proposed increase in viscosity with increasing F has now been experimentally confirmed.

  6. Light-load resistance exercise increases muscle protein synthesis and hypertrophy signaling in elderly men.

    Science.gov (United States)

    Agergaard, Jakob; Bülow, Jacob; Jensen, Jacob K; Reitelseder, Søren; Drummond, Micah J; Schjerling, Peter; Scheike, Thomas; Serena, Anja; Holm, Lars

    2017-04-01

    The present study investigated whether well-tolerated light-load resistance exercise (LL-RE) affects skeletal muscle fractional synthetic rate (FSR) and anabolic intracellular signaling as a way to counteract age-related loss of muscle mass. Untrained healthy elderly (>65-yr-old) men were subjected to 13 h of supine rest. After 2.5 h of rest, unilateral LL-RE, consisting of leg extensions (10 sets, 36 repetitions) at 16% of 1 repetition maximum (RM), was conducted. Subsequently, the subjects were randomized to oral intake of 4 g of whey protein per hour (PULSE, n = 10), 28 g of whey protein at 0 h and 12 g of whey protein at 7 h postexercise (BOLUS, n = 10), or 4 g of maltodextrin per hour (placebo, n = 10). Quadriceps muscle biopsies were taken at 0, 3, 7, and 10 h postexercise from the resting and the exercised leg of each subject. Myofibrillar FSR and activity of select targets from the mechanistic target of rapamycin complex 1-signaling cascade were analyzed from the biopsies. LL-RE increased myofibrillar FSR compared with the resting leg throughout the 10-h postexercise period. Phosphorylated (T308) AKT expression increased in the exercised leg immediately after exercise. This increase persisted in the placebo group only. Levels of phosphorylated (T37/46) eukaryotic translation initiation factor 4E-binding protein 1 increased throughout the postexercise period in the exercised leg in the placebo and BOLUS groups and peaked at 7 h. In all three groups, phosphorylated (T56) eukaryotic elongation factor 2 decreased in response to LL-RE. We conclude that resistance exercise at only 16% of 1 RM increased myofibrillar FSR, irrespective of nutrient type and feeding pattern, which indicates an anabolic effect of LL-RE in elderly individuals. This finding was supported by increased signaling for translation initiation and translation elongation in response to LL-RE. Copyright © 2017 the American Physiological Society.

  7. 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.

  8. Demand for Phenol Increases Steadily

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ Dramatic growth in output By the end of 2006 China's capacity to produce phenol had reached more than 600 thousand t/a. The total output was 523 thousand tons in 2006,an increase of 18.1% over 2005.

  9. Increasing Positive Interactive Classroom Behavior

    Science.gov (United States)

    Kotcher, Elaine; Doremus, Richard R.

    1973-01-01

    The question examined in this study was as follows: do teachers increase their positive classroom interactive behaviors as a result of training in systematic classroom observation techniques? (Authors/JA)

  10. Demand for SBR Increased Steadily

    Institute of Scientific and Technical Information of China (English)

    Gao Yiwen

    2007-01-01

    @@ 1 Rapid consumption growth Consumption of styrene-butadiene rubber (SBR) in China was 747 thousand tons in 2006, an increase of 21% over 2005, with faster growth than the average rubber consumption growth.

  11. AND INCREASED SMALLHOLDER PRODUCTIVITY IN

    African Journals Online (AJOL)

    ABSTRACT. Increases in agricultural productivity are fundamental to the sustainable development of many African economies .... scientists learn how to manage trees sustainably ... Today there are powerful tools that can be brought to bear on ...

  12. INCREASING RETURN TO SMART CITIES

    OpenAIRE

    Lööf, Hans; Nabavi, Pardis

    2012-01-01

    Increased urbanization, global warming and sustainable growth belong to the major contemporary policy challenges. Today cities are home to more than 50% of the world population, the largest 600 urban centers generate about 60% of global GDP, and the agglomerated areas are responsible for 75% of world carbon emissions. The UN estimates that 70% of the world's growing population will live in cities by 2050. At the same time the world population is expected to increase from 7 billion people to 9...

  13. RESTAURANT NO. 3 : PRICE INCREASES

    CERN Multimedia

    Restaurant Supervisory Committee

    2002-01-01

    'AVENANCE', the concession holder of Restaurant no. 3 (bldg. 866 - Prévessin site), has submitted to the Restaurant Supervisory Committee a request to increase its prices. After close examination, the Committee has established that the proposed increases are compatible with the relevant price indexing mechanisms and other contractual conditions. The new prices will apply as from Monday, June 3, 2002. Restaurant Supervisory Committee, tel. 77551

  14. No improvement of high-density lipoprotein (HDL) vasorelaxant effect despite increase in HDL cholesterol concentration in type 2 diabetic patients treated with glitazones.

    Science.gov (United States)

    Perségol, Laurence; Duvillard, Laurence; Monier, Serge; Brindisi, Marie-Claude; Bouillet, Benjamin; Petit, Jean-Michel; Vergès, Bruno

    2014-10-01

    High-density lipoproteins (HDLs) from type 2 diabetic patients are unable to counteract the inhibitory effect of oxidized low-density lipoproteins (ox-LDLs) on vasorelaxation. We hypothesized that glitazones, which improve glycemic control and dyslipidemia, could correct this abnormality. We compared the ability of HDL from controls (n = 12) and from type 2 diabetic patients before and after 6 months of treatment with either rosiglitazone (n = 11) or pioglitazone (n = 8) to counteract the inhibitory effect of ox-LDL on vasodilatation of rabbit aorta rings. Rosiglitazone induced a decrease in hemoglobin A1c (7.7% ± 1.1% vs 9.8% ± 1.0%, P = .003) and an increase in HDL cholesterol (1.14 ± 0.32 vs 0.98 ± 0.24 mmol/L, P = .033). Pioglitazone induced a decrease in hemoglobin A1c (8.3% ± 2.5% vs 9.5% ± 3.2%, P = .068) and serum triglycerides (1.58 ± 0.89 vs 2.03 ± 0.70 mmol/L, P = .069) and an increase in HDL cholesterol (1.39 ± 0.22 vs 1.14 ± 0.22 mmol/L, P = .018). The triglyceride content of HDL was unchanged by rosiglitazone and was decreased by 25% (P = .068) by pioglitazone. HDL from controls counteracted the inhibitory effect of ox-LDL on vasodilatation (maximal relaxation [Emax] = 74.4% ± 3.5% vs 51.9% ± 3.3%, P = .0029), whereas HDL from type 2 diabetic patients did not (Emax = 51.7% ± 5.8% vs 52.3% ± 4.6% [P = .66] and 52.7% ± 5.5% vs 51.9% ± 4.5% [P = .78] for the rosiglitazone and pioglitazone group, respectively). Rosiglitazone or pioglitazone did not improve Emax (58.6% ± 5.9% vs 52.3% ± 4.6% [P = .15] and 49.3% ± 6.5% vs 51.9% ± 4.5% [P = .48], respectively). Glitazones increased the concentration of HDL cholesterol without restoring the ability of HDL particles to protect the endothelium from oxidative stress-induced dysfunction, meaning that HDL remained dysfunctional with impaired antiatherogenic properties.

  15. 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.

  16. 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.

  17. 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.

  18. Retinoic acid increases glucocorticoid receptor phosphorylation via cyclin-dependent kinase 5.

    Science.gov (United States)

    Brossaud, Julie; Roumes, Hélène; Helbling, Jean-Christophe; Moisan, Marie-Pierre; Pallet, Véronique; Ferreira, Guillaume; Biyong, Essi-Fanny; Redonnet, Anabelle; Corcuff, Jean-Benoît

    2017-07-01

    Glucocorticoid receptor (GR) function is modulated by phosphorylation. As retinoic acid (RA) can activate some cytoplasmic kinases able to phosphorylate GR, we investigated whether RA could modulate GR phosphorylation in neuronal cells in a context of long-term glucocorticoid exposure. A 4-day treatment of dexamethasone (Dex) plus RA, showed that RA potentiated the (Dex)-induced phosphorylation on GR Serine 220 (pSer220GR) in the nucleus of a hippocampal HT22 cell line. This treatment increased the cytoplasmic ratio of p35/p25 proteins, which are major CDK5 cofactors. Roscovitine, a pharmacological CDK5 inhibitor, or a siRNA against CDK5 prevented RA potentiation of GR phosphorylation. Furthermore, roscovitine counter-acted the effect of RA on GR sensitive target proteins such as BDNF or tissue-transglutaminase. These data help understanding the interaction between RA- and glucocorticoid-signalling pathways, both of which have strong influences on the adult brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Contribution of aerobic step and Pilates exercises to life quality increase

    Directory of Open Access Journals (Sweden)

    Ancuța LUPĂU

    2017-03-01

    Full Text Available Physical activity practiced on a constant, regular basis contributes directly to the improvement of the structure and functions of different organs and body systems. It can also counteract the appearance of some anatomic and functional deterioration and contribute to the correction of certain deficiencies caused by improper conditions of life/work in people’s life. This study analyses two forms of physical exercise – Aerobic Step and Pilates. The goal of the study is to identify the effects of practicing Aerobic Step and Pilates exercises on the bodies of those who practice these forms of physical exercise. The hypothesis of the research is that practicing on constant/regular basis different types of aerobic exercises combined with efficient nutrition ensures optimum physical condition for everyday activities. The activity was carried out at the “Beauty Centre” aerobic hall from Timisoara, Romania. The study was carried out between February and May 2013 on a sample of 25 people subjected to anthropometric and functional measurements (size, weight, hip perimeter and body weight index, percentage of muscular tissue both before (initial test – It and after (final test – Ft Aerobic Step and Pilates programmes. Results show the efficiency of these programmes as pointed out by the diminution of hip perimeter, by normal IMC, and by the increase of the active muscular tissues.

  20. Weight cycling increases T-cell accumulation in adipose tissue and impairs systemic glucose tolerance.

    Science.gov (United States)

    Anderson, Emily K; Gutierrez, Dario A; Kennedy, Arion; Hasty, Alyssa H

    2013-09-01

    Obesity is one of the leading causes of morbidity in the U.S. Accumulation of proinflammatory immune cells in adipose tissue (AT) contributes to the development of obesity-associated disorders. Weight loss is the ideal method to counteract the negative consequences of obesity; however, losses are rarely maintained, leading to bouts of weight cycling. Fluctuations in weight have been associated with worsened metabolic and cardiovascular outcomes; yet, the mechanisms explaining this potential correlation are not known. For determination of whether weight cycling modulates AT immune cell populations, inflammation, and insulin resistance, mice were subjected to a diet-switch protocol designed to induce weight cycling. Weight-cycled mice displayed decreased systemic glucose tolerance and impaired AT insulin sensitivity when compared with mice that gained weight but did not cycle. AT macrophage number and polarization were not modulated by weight cycling. However, weight cycling did increase the number of CD4(+) and CD8(+) T cells in AT. Expression of multiple T helper 1-associated cytokines was also elevated subsequent to weight cycling. Additionally, CD8(+) effector memory T cells were present in AT of both obese and weight-cycled mice. These studies indicate that an exaggerated adaptive immune response in AT may contribute to metabolic dysfunction during weight cycling.

  1. Increased chromosome radiosensitivity during pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Ricoul, Michelle; Sabatier, Laure; Dutrillaux, Bernard [Commissariat a l`Energie Atomique, Laboratoire de Radiobiologie et Oncologie, DRR, DSV, Fontenay aux roses (France)

    1997-03-04

    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.

  2. 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......-operation with colleagues. In subgroup B and C, the participants ended up discussing the potential consequences of more work-time influence without actually implementing any changes. PRACTITIONER SUMMARY: Employee work-time influence may buffer the adverse effects of shift work. However, our intervention study suggested...... 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....

  3. Yohimbine increases human salivary secretion.

    Science.gov (United States)

    Chatelut, E; Rispail, Y; Berlan, M; Montastruc, J L

    1989-01-01

    The effect of oral yohimbine (14 mg) on salivary secretion was evaluated in healthy volunteers. Yohimbine significantly increased salivary secretion when compared with placebo. This effect was significant from 60 min until 180 min after administration under our experimental conditions. Yohimbine (or alpha 2-adrenoceptor blocking agents) could have a potential interest in the treatment of dry mouths. PMID:2789932

  4. Increasing Enrollment through Benefit Segmentation.

    Science.gov (United States)

    Goodnow, Betty

    1982-01-01

    The applicability of benefit segmentation, a market research technique which groups people according to benefits expected from a program offering, was tested at the College of DuPage. Preferences and demographic characteristics were analyzed and program improvements adopted, increasing enrollment by 20 percent. (Author/SK)

  5. Electromigration early resistance increase measurements

    OpenAIRE

    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 resistance decay (during recovery).

  6. Direct observation of increasing CO

    NARCIS (Netherlands)

    van Heuven, S.M.A.C.; Hoppema, M.; Huhn, O.; Slagter, H.A.; de Baar, H.J.W.

    2011-01-01

    The World Ocean takes up a large portion of the anthropogenic CO2 emitted into the atmosphere. Determining the resulting increase in dissolved inorganic carbon (C-T, expressed in mu mol kg(-1)) is challenging, particularly in the sub-surface and deep Southern Ocean where the time rate of change of

  7. Direct observation of increasing CO

    NARCIS (Netherlands)

    van Heuven, S.M.A.C.; Hoppema, M.; Huhn, O.; Slagter, H.A.; de Baar, H.J.W.

    2011-01-01

    The World Ocean takes up a large portion of the anthropogenic CO2 emitted into the atmosphere. Determining the resulting increase in dissolved inorganic carbon (C-T, expressed in mu mol kg(-1)) is challenging, particularly in the sub-surface and deep Southern Ocean where the time rate of change of C

  8. PMR Composites Of Increased Toughness

    Science.gov (United States)

    Vannucci, Raymond D.; Bowles, Kenneth J.

    1988-01-01

    Toughness increased without sacrificing processability or hot strength. Resin composition provides best overall balance of composite toughness and retention of mechanical properties at 600 degree F (316 degree C) with processability obtained by substituting 20 mole percent of diamine used in PMR-15 resins with diamine containing twice number of flexible phenyl connecting groups.

  9. Increasing Enrollment through Benefit Segmentation.

    Science.gov (United States)

    Goodnow, Betty

    1982-01-01

    The applicability of benefit segmentation, a market research technique which groups people according to benefits expected from a program offering, was tested at the College of DuPage. Preferences and demographic characteristics were analyzed and program improvements adopted, increasing enrollment by 20 percent. (Author/SK)

  10. Increasing Positive Interactive Classroom Behavior.

    Science.gov (United States)

    Kotcher, Elaine; Doremus, Richard R.

    During the spring of 1972 training workshops for 88 elementary and secondary teachers of the Great Neck Public Schools held to examine four hypotheses: 1) workshops in training teachers to observe classroom behavior would significantly increase these same teachers' positive classroom interactive behaviors consisting of teacher, pupil-pupil,…

  11. Increased Challenge with the Elderly.

    Science.gov (United States)

    Wilson, Helen

    Research has shown that too little stress or stimulation can increase health risks. To determine the effectiveness of mild stimulation on the depression levels and feelings of self-worth of the elderly, 24 withdrawn nursing home residents participated in a non-judgemental 6-month art expression group. Half the group were assigned to a control…

  12. Demand for ink Increases Rapidly

    Institute of Scientific and Technical Information of China (English)

    Song Guiqin

    2007-01-01

    @@ Output increased steadily China's ink sector has developed rapidlyin recent years.According to the NationalBureau of Statistics of China.China's ink output was 347.9 thousand tons in 2006,anincrease of 15.1% over 2005.

  13. 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.

  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. Cellular traction stresses increase with increasing metastatic potential.

    Directory of Open Access Journals (Sweden)

    Casey M Kraning-Rush

    Full Text Available Cancer cells exist in a mechanically and chemically heterogeneous microenvironment which undergoes dynamic changes throughout neoplastic progression. During metastasis, cells from a primary tumor acquire characteristics that enable them to escape from the primary tumor and migrate through the heterogeneous stromal environment to establish secondary tumors. Despite being linked to poor prognosis, there are no direct clinical tests available to diagnose the likelihood of metastasis. Moreover, the physical mechanisms employed by metastatic cancer cells to migrate are poorly understood. Because metastasis of most solid tumors requires cells to exert force to reorganize and navigate through dense stroma, we investigated differences in cellular force generation between metastatic and non-metastatic cells. Using traction force microscopy, we found that in human metastatic breast, prostate and lung cancer cell lines, traction stresses were significantly increased compared to non-metastatic counterparts. This trend was recapitulated in the isogenic MCF10AT series of breast cancer cells. Our data also indicate that increased matrix stiffness and collagen density promote increased traction forces, and that metastatic cells generate higher forces than non-metastatic cells across all matrix properties studied. Additionally, we found that cell spreading for these cell lines has a direct relationship with collagen density, but a biphasic relationship with substrate stiffness, indicating that cell area alone does not dictate the magnitude of traction stress generation. Together, these data suggest that cellular contractile force may play an important role in metastasis, and that the physical properties of the stromal environment may regulate cellular force generation. These findings are critical for understanding the physical mechanisms of metastasis and the role of the extracellular microenvironment in metastatic progression.

  16. The Dietary Constituent Falcarindiol Promotes Cholesterol Efflux from THP-1 Macrophages by Increasing ABCA1 Gene Transcription and Protein Stability

    Directory of Open Access Journals (Sweden)

    Limei Wang

    2017-09-01

    Full Text Available We report increased cholesterol efflux from macrophages in the presence of falcarindiol, an important dietary constituent present in commonly used vegetables and medicinal plants. Falcarindiol (3–20 μM increased cholesterol efflux from THP-1-derived macrophages. Western blot analysis showed an increased protein level of ABCA1 upon falcarindiol exposure. Quantitative real-time PCR revealed that also ABCA1 mRNA level rise with falcarindiol (10 μM treatment. The effect of falcarindiol on ABCA1 protein as well as mRNA level were counteracted by co-treatment with BADGE, an antagonist of PPARγ. Furthermore, falcarindiol significantly inhibited ABCA1 protein degradation in the presence of cycloheximide. This post-translational regulation of ABCA1 by falcarindiol occurs most likely by inhibition of lysosomal cathepsins, resulting in decreased proteolysis and extended protein half-life of ABCA1. Taken together, falcarindiol increases ABCA1 protein level by two complementary mechanisms, i.e., promoting ABCA1 gene expression and inhibiting ABCA1 protein degradation, which lead to enhanced cholesterol efflux.

  17. Increasing Accuracy in Environmental Measurements

    Science.gov (United States)

    Jacksier, Tracey; Fernandes, Adelino; Matthew, Matt; Lehmann, Horst

    2016-04-01

    Human activity is increasing the concentrations of green house gases (GHG) in the atmosphere which results in temperature increases. High precision is a key requirement of atmospheric measurements to study the global carbon cycle and its effect on climate change. Natural air containing stable isotopes are used in GHG monitoring to calibrate analytical equipment. This presentation will examine the natural air and isotopic mixture preparation process, for both molecular and isotopic concentrations, for a range of components and delta values. The role of precisely characterized source material will be presented. Analysis of individual cylinders within multiple batches will be presented to demonstrate the ability to dynamically fill multiple cylinders containing identical compositions without isotopic fractionation. Additional emphasis will focus on the ability to adjust isotope ratios to more closely bracket sample types without the reliance on combusting naturally occurring materials, thereby improving analytical accuracy.

  18. Plant genetics: increasing crop yield.

    Science.gov (United States)

    Day, P R

    1977-09-30

    Cell cultures of crop plants provide new opportunities to recover induced mutations likely to increase crop yield. Approaches include regulating respiration to conserve carbon fixed by photosynthesis, and increasing the nutritive value of seed protein. They depend on devising selecting conditions which only desired mutant cells can survive. Protoplast fusion offers some promise of tapping sources of genetic variation now unavailable because of sterility barriers between species and genera. Difficulties in regenerating cell lines from protoplasts, and plants from cells, still hamper progress but are becoming less severe. Recombinant DNA techniques may allow detection and selection of bacterial cell lines carrying specific DNA sequences. Isolation and amplification of crop plant genes could then lead to ways of transforming plants that will be useful to breeders.

  19. Increase voted to NSF Budget

    Science.gov (United States)

    Richman, Barbara T.

    The Subcommittee on Science, Research, and Technology of the House Committee on Science and Technology voted by a narrow margin on March 10 to increase the National Science Foundation (NSF) budget authorization by $30 million, pushing the total budget to $1099.5 million. The increase is targeted solely for science and engineering education (see table). Although the total for research and related activities in NSF remained the same as in President Reagan's budget request, the subcommittee shifted funds among directorates, including an $8.9 million decrease from the budget of the Directorate for Astronomical, Atmospheric, Earth, and Ocean Sciences (AAEO). The subcommittee action also calls for $1.6 million to be allocated to United States participation in the International Institute for Applied Systems Analysis (NASA).

  20. Production Increased with Higher Prices

    Institute of Scientific and Technical Information of China (English)

    Feng shiling

    2007-01-01

    @@ In the first quarter of 2007, China's petroleum and chemical industry remained up trend in production.Among the 66 types of petrochemical products that have been tracked by CPCIA (China Petroleum and Chemical Industry Association), the output of 58, types increased compared with the same period of 2006, accounting for 87.9% of the total, and the output of 19 types, in particular, grew by over20%, accounting for 28.8%.

  1. 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...

  2. [Increasing interest in cold therapy].

    Science.gov (United States)

    Johansson, Bengt W

    2002-01-31

    Hypothermia was used early in the treatment of malignant tumors. New evidence shows that hypothermia protects normal tissues from the toxic effects of radiation and chemotherapeutic drugs. Hypothermia in oncological research is calculated to increase the therapeutic ratio by protecting normal tissue while retaining the antineoplastic effect. Animal results indicate that removal of the primary tumor using cryosurgery diminishes metastatic tumor growth more than does surgical excision.

  3. Experiencing discrimination increases risk taking.

    Science.gov (United States)

    Jamieson, Jeremy P; Koslov, Katrina; Nock, Matthew K; Mendes, Wendy Berry

    2013-02-01

    Prior research has revealed racial disparities in health outcomes and health-compromising behaviors, such as smoking and drug abuse. It has been suggested that discrimination contributes to such disparities, but the mechanisms through which this might occur are not well understood. In the research reported here, we examined whether the experience of discrimination affects acute physiological stress responses and increases risk-taking behavior. Black and White participants each received rejecting feedback from partners who were either of their own race (in-group rejection) or of a different race (out-group rejection, which could be interpreted as discrimination). Physiological (cardiovascular and neuroendocrine) changes, cognition (memory and attentional bias), affect, and risk-taking behavior were assessed. Significant participant race × partner race interactions were observed. Cross-race rejection, compared with same-race rejection, was associated with lower levels of cortisol, increased cardiac output, decreased vascular resistance, greater anger, increased attentional bias, and more risk-taking behavior. These data suggest that perceived discrimination is associated with distinct profiles of physiological reactivity, affect, cognitive processing, and risk taking, implicating direct and indirect pathways to health disparities.

  4. 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.

  5. Revising probability estimates: Why increasing likelihood means increasing impact.

    Science.gov (United States)

    Maglio, Sam J; Polman, Evan

    2016-08-01

    Forecasted probabilities rarely stay the same for long. Instead, they are subject to constant revision-moving upward or downward, uncertain events become more or less likely. Yet little is known about how people interpret probability estimates beyond static snapshots, like a 30% chance of rain. Here, we consider the cognitive, affective, and behavioral consequences of revisions to probability forecasts. Stemming from a lay belief that revisions signal the emergence of a trend, we find in 10 studies (comprising uncertain events such as weather, climate change, sex, sports, and wine) that upward changes to event-probability (e.g., increasing from 20% to 30%) cause events to feel less remote than downward changes (e.g., decreasing from 40% to 30%), and subsequently change people's behavior regarding those events despite the revised event-probabilities being the same. Our research sheds light on how revising the probabilities for future events changes how people manage those uncertain events. (PsycINFO Database Record

  6. 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

  7. THE PROBLEMS OF THE INCREASE OF EFFICIENCY OF ACTIVITY OF POLICE ORGANS OF ECONOMICAL SAFETY PROVISION IN THE REGIONS OF RUSSIA

    Directory of Open Access Journals (Sweden)

    V.J. Panteleyev

    2008-06-01

    Full Text Available At the article the problems of provision economical safety of the consumer market sphere are discussed. The author defines of legal relations of consumer market sphere as legal regulation of sphere of production and trade goods (works, services, provision of protection rights, interests, life, health, safety of material and spiritual consumption of population and also economic, ecological, product, other kinds of national safety of Russian Federations. He analyses the condition of economical crimes of Sverdlovsk region and the Ural Federal District and its influence on shadow economy. He offers the measures increasing interaction between government bodies of Russian Federation and subjects RF, the measures altering legislation and application the innovation technologies for counteraction economical crimes. In the author’s opinion these measures have to foresee the development of state programmes of support of small business in consumer market sphere.

  8. Increased NMDA receptor inhibition at an increased Sevoflurane MAC.

    Science.gov (United States)

    Brosnan, Robert J; Thiesen, Roberto

    2012-06-06

    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. 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. 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 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.

  9. [How to increase food production?].

    Science.gov (United States)

    Gahamanyi, L

    1984-12-01

    Pressure of population on cultivable land, serious soil erosion, and low productivity due to scarcity of inputs have hampered efforts to provide an adequate diet for the population of Rwanda. Until the present, production has increased about as rapidly as population, but Rwanda is not totally self-sufficient in food, future climatic conditions may be less favorable than those of the past, technical and resource constraints are likely to increase, and little new land will be available for cultivation. Between 1970-80, hectares devoted to bananas and beans have increased considerably, but the marginal nature of much new land has seriously lowered productivity. Sweet potatoes are more extensively grown but their productivity is limited, and productivity of manioc has stagnated despite efforts to increase it. Peas are less frequently cultivated because the fallow land on they they are grown has almost disappeared due to population pressure. Agriculture in Rwanda has always been associated with herding, but population pressure is eliminating pastureland. Firewood for cooking is also becoming more scarce and reforestation is not proceeding rapidly enough to fill projected demand. Between 1978-80 and the year 2000, preliminary goals are to increase production in tons from 2,005,900 to 3,375,000 for bananas, from 177,400 to 330,000 for beans, from 15,200 to 45,500 for ground nuts, from 4000 to 25,000 for soybeans, from 174,800 to 288,000 for sorghum, from 81,300 to 250,000 for maize, from 3700 to 45,000 for rice, from 837,100 to 2,148,000 for sweet potatoes, from 506,600 to 1,200,000 for manioc, and from 216,000 to 600,000 for potatoes. Reaching these goals will require doubling of overall productivity per hectare. Different strategies will be required for increasing the yields of the principal crops. Priority should be given to developing strains of beans that will grow well in the poor soils, dry or cold regions, and acidic soils where they are usually planted in Rwanda

  10. Increase Productivity Through Knowledge Management

    Science.gov (United States)

    Gavrikova, N. A.; Dolgih, I. N.; Dyrina, E. N.

    2016-04-01

    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 problem: the main sources of knowledge in engineering enterprise have been defined, the conditions of success and the stages of knowledge management control have been stated.

  11. Prostacyclin Increases Portal Venous Flow.

    Science.gov (United States)

    1984-07-01

    response curve . We2 constructed a dose response curve by using increasing doses of PGI (0.005, 0.05, 0.5, and 5.0 ug/kg) given through the left atrial...atropine 0 40- +1 S20- X ( 0- * -20 -40 , 0.005 0.05 0.5 5.0 DOSE jig/kg Figure 2A (top). The log dose response curve of femoral artery pressure (FAP...Figure 2B (bottom). The log dose response curve of {. pulmonary artery pressure (PAP). Both figures show the maximum . deviation from baseline

  12. Increasing production at Cerrejon Central

    Energy Technology Data Exchange (ETDEWEB)

    Climent, J.; Alvarez, M.

    1997-12-01

    Colombian coal miner Prodeco is hoping to increase production of its opencast Cerrejon Central mine from 3.1 Mt in 1996 to 10 Mt by 2002. This article discusses how this is to be achieved. The development programme, presently in Phase II of three phases, will affect not only the mine itself but also include improvements to loading facilities at Santa Marta port, at the company`s head office, and construction of a new port nearby. 3 figs., 2 tabs., 3 photos.

  13. 逍遥散抗慢性应激损伤中枢Glu-NR-Ca2+-GR信号通路机制探讨%Study on Central Glu-NR-Ca2+-GR Signaling Pathway Mechanism of Xiaoyao Powder on Counteracting Chronic Stress

    Institute of Scientific and Technical Information of China (English)

    孙琪; 敖海清; 富文俊; 郭维

    2011-01-01

    each group of the cultured cells according to the experimental design, and mRNA expression of the subunits of N-methyl-D-aspartate (NMDA) receptor, concentration of intracellular free Ca2+, expression of intracellular glucocorticoid receptor(iGR) and the correlation among all these indexes were studied. Results NR1, NR2A and NR2B mRNA were increased to various degrees, concentration of free Ca2+ intracellular was increased significantly, and the protein expression of iGR was decreased significantly when glutamate and serum of rat model with chronic stress acted together on the cultured hippocampal neurons. Expression of NR2A mRNA was upregulated significantly but that of NR2B mRNA was down-regulated , concentration of free Ca2+ intracellular was decreased significantly and chronic stress-induced downregula-tion of iGR was councteracted significantly when serum of chronic stress rats treated with XP acted on the neurons, which showed synergistic action with dizocilpine to some extent. Conclusion The state of chronic stress micro-envi-ronment could be simulated by using serum of chronic stress rat model together with glutamate for the culture of hip-pocampal neurons. XP-treated serum could correct the imbalance state of the NR subunits mRNA expression, maintain the normal proportion of NR2A and NR2B and intracellular calcium homeostasis, and counteract the decrease of iGR expression caused by chronic stress. XP plays a role in maintaining stability of hippocampal nerve cells, and the preventive mechanism may be associated with multiple signaling pathways including that of Glu-NR-Ca2+- iGR.

  14. Increasing Coverage of Appropriate Vaccinations

    Science.gov (United States)

    Jacob, Verughese; Chattopadhyay, Sajal K.; Hopkins, David P.; Morgan, Jennifer Murphy; Pitan, Adesola A.; Clymer, John

    2016-01-01

    Context Population-level coverage for immunization against many vaccine-preventable diseases remains below optimal rates in the U.S. The Community Preventive Services Task Force recently recommended several interventions to increase vaccination coverage based on systematic reviews of the evaluation literature. The present study provides the economic results from those reviews. Evidence acquisition A systematic review was conducted (search period, January 1980 through February 2012) to identify economic evaluations of 12 interventions recommended by the Task Force. Evidence was drawn from included studies; estimates were constructed for the population reach of each strategy, cost of implementation, and cost per additional vaccinated person because of the intervention. Analyses were conducted in 2014. Evidence synthesis Reminder systems, whether for clients or providers, were among the lowest-cost strategies to implement and the most cost effective in terms of additional people vaccinated. Strategies involving home visits and combination strategies in community settings were both costly and less cost effective. Strategies based in settings such as schools and managed care organizations that reached the target population achieved additional vaccinations in the middle range of cost effectiveness. Conclusions The interventions recommended by the Task Force differed in reach, cost, and cost effectiveness. This systematic review presents the economic information for 12 effective strategies to increase vaccination coverage that can guide implementers in their choice of interventions to fit their local needs, available resources, and budget. PMID:26847663

  15. 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.

  16. Public knowledge about AIDS increasing.

    Science.gov (United States)

    Campbell, M J; Waters, W E

    1987-04-04

    In response to concern over the perceived limited effectiveness of Department of Health and Social Security (UK) advertising campaigns to inform the public of the basic facts of Acquired Immunodeficiency Syndrome (AIDS), a prospective questionnaire study was undertaken in Southampton, England to test the effectiveness of government education prior to a January, 1987 government television/leaflet advertising campaign. 300 questionnaires about AIDS were mailed in December of 1986 to a sample drawn from electoral rolls. The response rate was 61%. Most of the questions were drawn from material covered in the campaign. The results seemed to indicate a small overall increase in knowledge about AIDS. Some changes from a June survey were noted, e.g.: more people were aware that AIDS is a virus for which there is no cure and that it is not readily transmitted by sharing washing, eating or drinking utensils; more people believed that the statement that women are at greater risk for catching AIDS is false. Respondents were generally favorable to the government's continued use of television, even with explicit language, and to its use of the schools, for AIDS education. Many were not aware of the dangers to intravenous drug users or of the symptoms of AIDS. Other surveys have shown an increasing knowledge of AIDS dangers. It is possible that television coverage of the problem will continue to be necessary, in order that less literate populations be reached. Further AIDS health education in general is needed.

  17. 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

  18. 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

  19. Increase in composite binder activity

    Science.gov (United States)

    Fediuk, R.; Smoliakov, A.; Stoyushko, N.

    2016-11-01

    The binder of portland cement (51-59 wt.%), fly ash of thermal power stations (3644 wt.%), limestone crushing waste (4-9 wt.%) and dry hyper plasticizer (0.2 wt.%) has been created. It can be used in the building materials industry for production of high-strength concrete. The composite binder is obtained by co-milling of the components in vario-planetary mill to a specific surface area of 550-600 m2/kg. The technical result is the possibility of obtaining a composite binder with significant replacement of cement with industrial waste, cost-effective and superior to portland cement for construction and technical properties, increased activity. This allows producing concrete for walling with a compressive strength of 100 MPa, while using more than 50% of industrial waste.

  20. Increasing entropy for colloidal stabilization

    Science.gov (United States)

    Mo, Songping; Shao, Xuefeng; Chen, Ying; Cheng, Zhengdong

    2016-11-01

    Stability is of paramount importance in colloidal applications. Attraction between colloidal particles is believed to lead to particle aggregation and phase separation; hence, stability improvement can be achieved through either increasing repulsion or reducing attraction by modifying the fluid medium or by using additives. Two traditional mechanisms for colloidal stability are electrostatic stabilization and steric stabilization. However, stability improvement by mixing attractive and unstable particles has rarely been considered. Here, we emphasize the function of mixing entropy in colloidal stabilization. Dispersion stability improvement is demonstrated by mixing suspensions of attractive nanosized titania spheres and platelets. A three-dimensional phase diagram is proposed to illustrate the collaborative effects of particle mixing and particle attraction on colloidal stability. This discovery provides a novel method for enhancing colloidal stability and opens a novel opportunity for engineering applications.

  1. Moire interferometry with increased sensitivity

    Science.gov (United States)

    Han, Bongtae; Post, Daniel

    The basic sensitivity of moire interferometry was increased beyond the previously conceived theoretical limit. This was accomplished by creating the virtual reference grating inside a refractive medium instead of air, thus shortening the wavelength of light. A very compact four-beam moire interferometer in a refractive medium was developed for microscopic viewing, which produced a basic sensitivity of 208 nm per fringe order, corresponding to moire with 4800 lines per mm. Its configuration made it inherently stable and relatively insensitive to environmental disturbances. An optical microscope was employed as the image recording system to obtain high spatial resolution. The method was demonstrated for deformation of a thick graphite/epoxy composite at the 0/90 deg ply interface.

  2. Propofol directly increases tau phosphorylation.

    Directory of Open Access Journals (Sweden)

    Robert A Whittington

    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

  3. 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

    Directory of Open Access Journals (Sweden)

    Sara Marie Atkinson

    2016-04-01

    Full Text Available 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

  4. Vocal attractiveness increases by averaging.

    Science.gov (United States)

    Bruckert, Laetitia; Bestelmeyer, Patricia; Latinus, Marianne; Rouger, Julien; Charest, Ian; Rousselet, Guillaume A; Kawahara, Hideki; Belin, Pascal

    2010-01-26

    Vocal attractiveness has a profound influence on listeners-a bias known as the "what sounds beautiful is good" vocal attractiveness stereotype [1]-with tangible impact on a voice owner's success at mating, job applications, and/or elections. The prevailing view holds that attractive voices are those that signal desirable attributes in a potential mate [2-4]-e.g., lower pitch in male voices. However, this account does not explain our preferences in more general social contexts in which voices of both genders are evaluated. Here we show that averaging voices via auditory morphing [5] results in more attractive voices, irrespective of the speaker's or listener's gender. Moreover, we show that this phenomenon is largely explained by two independent by-products of averaging: a smoother voice texture (reduced aperiodicities) and a greater similarity in pitch and timbre with the average of all voices (reduced "distance to mean"). These results provide the first evidence for a phenomenon of vocal attractiveness increases by averaging, analogous to a well-established effect of facial averaging [6, 7]. They highlight prototype-based coding [8] as a central feature of voice perception, emphasizing the similarity in the mechanisms of face and voice perception.

  5. 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.

  6. Increased inflammatory effect of electronegative LDL and decreased protection by HDL in type 2 diabetic patients.

    Science.gov (United States)

    Estruch, Montserrat; Miñambres, Inka; Sanchez-Quesada, Jose Luis; Soler, Marta; Pérez, Antonio; Ordoñez-Llanos, Jordi; Benitez, Sonia

    2017-10-01

    Type 2 diabetic patients have an increased proportion of electronegative low-density lipoprotein (LDL(-)), an inflammatory LDL subfraction present in blood, and dysfunctional high-density lipoprotein (HDL). We aimed at examining the inflammatory effect of LDL(-) on monocytes and the counteracting effect of HDL in the context of type 2 diabetes. This was a cross-sectional study in which the population comprised 3 groups (n = 12 in each group): type 2 diabetic patients with good glycaemic control (GC-T2DM patients), type 2 diabetic patients with poor glycaemic control (PC-T2DM), and a control group. Total LDL, HDL, and monocytes were isolated from plasma of these subjects. LDL(-) was isolated from total LDL by anion-exchange chromatography. LDL(-) from the three groups of subjects was added to monocytes in the presence or absence of HDL, and cytokines released by monocytes were quantified by ELISA. LDL(-) proportion and plasma inflammatory markers were increased in PC-T2DM patients. LDL(-) from PC-T2DM patients induced the highest IL1β, IL6, and IL10 release in monocytes compared to LDL(-) from GC-T2DM and healthy subjects, and presented the highest content of non-esterified fatty acids (NEFA). In turn, HDL from PC-T2DM patients showed the lowest ability to inhibit LDL(-)-induced cytokine release in parallel to an impaired ability to decrease NEFA content in LDL(-). Our findings show an imbalance in the pro- and anti-inflammatory effects of lipoproteins from T2DM patients, particularly in PC-T2DM. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. 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.

  8. 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

    2017-09-20

    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.

  9. Decreased PGE₂ content reduces MMP-1 activity and consequently increases collagen density in human varicose vein.

    Directory of Open Access Journals (Sweden)

    Ingrid Gomez

    Full Text Available Varicose veins are elongated and dilated saphenous veins. Despite the high prevalence of this disease, its pathogenesis remains unclear.In this study, we investigated the control of matrix metalloproteinases (MMPs expression by prostaglandin (PGE₂ during the vascular wall remodeling of human varicose veins.Varicose (small (SDv and large diameter (LDv and healthy saphenous veins (SV were obtained after surgery. Microsomal and cytosolic PGE-synthases (mPGES and cPGES protein and mRNA responsible for PGE₂ metabolism were analyzed in all veins. cPGES protein was absent while its mRNA was weakly expressed. mPGES-2 expression was similar in the different saphenous veins. mPGES-1 mRNA and protein were detected in healthy veins and a significant decrease was found in LDv. Additionally, 15-hydroxyprostaglandin dehydrogenase (15-PGDH, responsible for PGE₂ degradation, was over-expressed in varicose veins. These variations in mPGES-1 and 15-PGDH density account for the decreased PGE₂ level observed in varicose veins. Furthermore, a significant decrease in PGE₂ receptor (EP4 levels was also found in SDv and LDv. Active MMP-1 and total MMP-2 concentrations were significantly decreased in varicose veins while the tissue inhibitors of metalloproteinases (TIMP -1 and -2, were significantly increased, probably explaining the increased collagen content found in LDv. Finally, the MMP/TIMP ratio is restored by exogenous PGE₂ in varicose veins and reduced in presence of an EP4 receptor antagonist in healthy veins.In conclusion, PGE₂ could be responsible for the vascular wall thickening in human varicose veins. This mechanism could be protective, strengthening the vascular wall in order to counteract venous stasis.

  10. 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.

  11. 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